2.1. Introduction - INFLIBNETshodhganga.inflibnet.ac.in/bitstream/10603/9082/11/12_chapter 2.pdf ·...

Synthesis and Antifungal Activity of Novel Azido and 1,2,3-Triazole containing Coumarins

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2.1. Introduction

The ever-increasing demand for novel biologically-active compounds and the laborious

process of lead discovery and optimization have resulted in the continuous search for

simple and efficient methods for generating libraries for biological screening. Last

decades have witnessed increasing effort for developing new antifungal drugs that are

capable to inhibit various diseases related to Candida albicans species, considered to be

responsible for the most common type of human pathogenic fungi. Fungal infections are

reported to cause a lot of morbidity and mortality despite recent advances in antifungal

chemotherapeutic regimen.1 This is due to greater use of immunosuppressive drugs,

prolonged use of broad-spectrum of antibiotics for various conditions including cancer

patients and organ transplants.

2.2. Antifungal agents

Fungi are insidious pathogens because they are eukaryotic microorganisms: they are

more closely related to human cells, and are thus more difficult to target with antifungal

chemotherapy. Fungal infections (mycoses) can further be divided into superficial and

systemic types. The first group includes cosmetically unpleasant but less serious

infections of the skin, nails and hair shafts caused by dermatophytes or yeast. On the

other hand, systemic infections such as torulosis and aspergillosis are potentially fatal,

and are a growing danger for human health.2,3

They occur more frequently in individuals

with compromised immune system (AIDS patients, transplant patients, cancer patients).

The most common pathogenic agents that cause invasive fungal infections are Candida

and Aspergillus.4,5

It is, therefore, imperative to diagnose these infections at an early

stage and treat them effectively. The drugs derived from natural sources or prepared

synthetically are available for treating the fungal infections; however none of these drugs

is ideal. For many years, the only available antifungal was amphotericin B 16 or its

combination with nystatin 2,7 which are considered to be the drugs of choice at present

and remain effective therapeutic agent in severe conditions of invasive mycosis but have

been found to be highly toxic and immunosuppressive.8 ,9

The non-availability of an

absorbable oral form of amphotericin B for long maintenance therapy in

immunocompromised patients is another important drawback of this drug.


2

Amphotericin B (1)

Nystatin (2)

Antifungal are those agents that destroy the growth of pathogenic fungi and are used as a

medication to treat fungal infections such as athlete’s foot, ringworm, candidiasis

(thrush), serious systemic infections such as cryptococcal meningitis and others.

Antifungal drugs target ergosterol (3) or the steps in its synthesis (Table 1, Figure 1).

Ergosterol (3), the functional fungal analogue of cholesterol in animal cells, is found in

the fungal cell membrane, where it has essential roles in the modulation of membrane

fluidity and as a signal for cell division. Because ergosterol has different chemical

properties from cholesterol, it has been exploited as a target for antifungal drugs, which

are incorporated into fungal cell membranes containing ergosterol, but are less readily

incorporated into host cell membranes, which contain cholesterol (4). In addition to

ergosterol itself, there are several enzymatic steps that are unique to ergosterol synthesis

and are also the targets for antifungal drugs; however, apart from ergosterol and its

biosynthesis, there are few other targets that can be exploited in antifungal therapy.10


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Ergosterol (3) Cholesterol (4)

Figure 1: Sterol molecules present in mammalian and fungal cell membranes

Table 1: Antifungal agents: activities, mode of action and resistance mechanism

Antifungal agents

(Figure 2)

Spectrum of

activity

Mode of action Resistance

mechanism

Polyenes

Amphotericin B (1) Broad activity

against Candida spp.,

except C. lusitaniae;

Cryptococcus

neoformans and

filamentous fungi,

exceptA. terreus and

A. flavus.

Binding to

ergosterol and

destabilization of

cell membrane

functions

Alteration in

specific steps of

ergosterol

biosynthesis

Pyrimidine analogues

5-Fluorocytosine

(5)

Active against

Candida spp. and

Cryptococcus spp.;

however, rapid

emergence of

resistance can

appear when 5-FC

is used as

monotherapy

Impairment of

nucleic acid

biosynthesis by

formation of toxic

fluorinated

pyrimidine

antimetabolites

Decreased uptake of

5-FC; decreased

formation of toxic

antimetabolites.

Azoles

Fluconazole (6) Active against

Candida spp. and

Cryptococcus spp.;

less active against

Inhibition of

cytochrome P450

14α-lanosterol

demethylase

Enhanced efflux by

upregulation of

multidrug.


4

C. glabrata and no

activity against C.

krusei; no activity

against filamentous

fungi

Itraconazole (7) Like fluconazole,

but enhanced

activity against

filamentous fungi

Inhibition of

cytochrome P450

14α-lanosterol

demethylase

Target alterations by

occurrence of

mutations

Voriconazole (8) Like fluconazole,

but enhanced

activity against

filamentous fungi,

including

Aspergillus and

Fusarium spp.

- Alteration of

specific steps in the

ergosterol

biosynthesis

pathway

Posaconazole (9) Closely related to

itraconazole, but

more active

- -

Allylamines

Terbinafine (10) Active against most

dermatophytes,

poor activity against

Candida spp.

Inhibition of

squalene epoxidase

Unknown

Morpholines

Amorolfine (11) Active against most

dermatophytes,

poor activity against

Candida spp.

Inhibition of sterol

∆14

reductase and

∆7,8

isomerase

Unknown

Echinocandins

Anidulafungin (12) Active against

Candida spp. With

fungicidal activity,

moderately active

against Aspergillus

spp., poor activity

against C.

neoformans

Inhibition of the cell

wall synthesis

enzymeβ-1,3 glucan

synthase

Unknown


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Figure 2

2.3. Biological properties of 1,2,3-triazoles

Triazole derivatives are known to exhibit various pharmacological properties such as

anti-microbial,11

anti-tubercular,12

anti-cancer,13

anti-convulsant,14

anti-inflammatory,

analgesic15

and anti-viral.16

Triazoles have also been incorporated in a wide variety of

therapeutically interesting drugs including H1/H2 histamine receptor blockers, CNS


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stimulants, anti-anxiety agents and sedatives.17

Potential pharmaceuticals based on 1,2,3-

triazoles include the anticancer compound carboxyamidotriazole (CAI) (13), the

nucleoside derivative non-nucloside reverse transcriptase inhibitor tert-

butyldimethylsilylspiroaminooxathioledioxide known as TSAO (14), β-lactum antibiotic

Tazobactum (15) and the cephalosporine Cefatrizine (16) (Figure 3).Structure activity

relationships have revealed that bioisosteric replacement of a triazole ring leads to

antifungal activity with a higher selectivity of the fungal targets. Triazole antifungal

drugs are used in the treatment of both superficial and deepseated candidiasis.18

Figure 3: Potential pharmaceuticals based on 1,2,3-triazoles.

A series of triazole-containing novobiocin analogues (17) were designed, synthesized,

and their biological activity was determined by Peterson and co-workers.19

The anti-

proliferative effects of these compounds were evaluated against two breast-cancer cell

lines (SKBr-3 and MCF-7) and displayed IC50 values above 50 μm. In this case, triazole

moiety affects biological activity in two ways: the availability of a hydrogen-bond donor

in the amide linkage and the steric bulk of the side chain. HIV-1 protease (HIV-1-Pr) has

been recognized as an important target for inhibition of viral replication. A library of 1,4-

disubstituted-1,2,3-triazoles (18) was synthesized by Whiting et al.20

These compounds

exhibited high binding efficiency to human immunodeficiency virus type-1 protease

(HIV-1-Pr). 1,2,3-Triazole-containing compounds such as 19, has been reported


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aspotential dual-action HIV-1 protease and non-nucleoside reverse transcriptase

inhibitors.21

Two series of 1,2,3-triazole compounds with anti-mycobacterium profile

were reported by Costa et al.22

The in vitro anti-tubercular activity screening of these

series showed that the triazole-4-carbaldehyde derivatives (20A) were more effective

than the 4-difluoromethyl derivatives (20B). 1-(2,3-Dihydrobenzofuran-2-yl-methyl-

1,2,3-triazoles (21)23

showed antitubercular activity against Mycobacterium tuberculosis

H37Rv with minimum inhibitory concentration (MIC) values ranging from 12.5 to 3.12

μgmL-1

. Novel H37Rv strain inhibitors with fluorine and 1,2,3-triazole containing

benzimidazoles (22) for the treatment of tuberculosis were disclosed by Gill et al24

(Figure 4).

Figure 4

2.3.1. As Antifungal and Antibacterial Agents

Vatmurge et al.25

have reported the synthesis of novel 1,2,3-triazole-linked with β-

lactam–bile acid conjugates (23, Figure 5) which inhibit significant antifungal activity

against different fungal strains such as Candida albicans, Cryptococcusneoformans,

Benjaminiella poitrasii, Yarrowia lipolytica and Fusarium oxysporum. The triazole

derivatives 24 and 25 showed the best antifungal activity against Candida albicans.26

The


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fluconazole-based novel mimics 2627

and 27 that contained 1,2,3-triazole were found to

be more potent against Candida fungal pathogens than control drugs fluconazole and

amphotericin B with MIC values ranging from 3.12 to 6.25 mg ml-1

. These molecules

were evaluated in vitro against Candida albicans intravenous challenge in Swiss mice,

and antiproliferative activities were tested against human hepatocellular carcinoma

Hep3B cells and human epithelial carcinoma A431 cells. It was found that a compound

with a long alkyl chain resulted in 97.4% reduction in fungal load in mice and did not

show any profound proliferative effect at lower dosage (0.001 mg mL-1

). Triazole

glycosides (28) detected in subsequent bioassays showed promising antifungal activity.28

Figure 5

2.4. Coumarin(Benzopyran-2-one)

Coumarins are phenolic substances made of fused benzene and α-pyrone rings.

Benzopyran-2-ones (coumarins) form an elite class of compounds, which occupy a

special role in nature. Coumarins and their derivatives have been found to exhibit a

variety of biological and pharmacological activities and have raised considerable interest

because of their potential beneficial effects on human health. They have been reported to

possess among others: anti-HIV, anti-coagulant, anti-bacterial, anti-cancer, anti-

inflammatory and anti-oxidant activities. Among all these activities, anti-fungal activity

is of particular interest.


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2.4.1. Coumarin as antifungal

Coumarins are known potential growth inhibitors of bacteria and fungi, where both

natural and synthetic coumarins inhibit growth of common microorganisms Candida

albicans, Escherichia coli and Staphylococcus aureus. Plant coumarins also bear

antimicrobial potential and have been reported to stimulate macrophages which could

have an indirect negative effect on infections. Hydroxycoumarin scopoletin 29 was

isolated from seed kernels of Melia azedarach29

reported to be antifungal against

Fusarium verticillioides. Deng and Nicholson30

reported the antifungal properties of

surangin B 30, a coumarin from Mammea longifolia. Phytoalexins, which are

hydroxylated derivatives of coumarins, are produced in carrots in response to fungal

infection and can be presumed to have antifungal activity31

. A coumarin namely, 6,7-

dimethoxycoumarin 31, isolated from P. digitatum-infected Valencia fruit confers

resistance against the mycotoxigenic fungi A. parasiticus32

. Clausenidin 32, dentatin, nor-

dentatin, and carbazole alkaloid clauszoline J 33 isolated from Clausena excavata

showed antimycotic activity (MIC 50 μg/mL). Angelicin, 34 a naturally occurring

furanocoumarin, which showed antifungal activity, was considered as a lead structure for

a group of synthetic coumarins.33

In many of the synthesized coumarins and angular

furanocoumarins, the free 6-OH was found to be important for antifungal activity.In a

series of 6,7,8 tri-substituted coumarin derivatives compound 35 has the strongest and

broadest spectrum of activity. This compound is also the only one in this group with a

free 6-OH, which probably contributes to its potency. Substitution of an alkyl group at C-

8 position of 35 results in the increase of antifungal properties compared to 36 (Figure

6). Prenylated coumarin isolated from leaf extract of Baccharis pedunculata have been

identified as active against some human pathogenic fungi.34

Some synthetic coumarin

derivatives have also been reported to be active against the yeast C. albicans.35

Herniarin

(7-methoxycoumrin) has shown activity against Aspergillus glaucus and Aspergillus

flavus.36


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Figure 6

2.5. Past work on Synthesis of Coumarin-triazole derivatives

The electron-donating properties of the triazole ring formed in the azide-alkyne ligation

reaction can be effectively utilized for the design of a chemoselective fluorogenic probe

that may find a range of applications in biology, analytical chemistry, or material science.

Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction was applied for linking azide

unit 38 to coumarin derivative with terminal alkyne functionality 37 to synthesize a new

fluorescent probe 39, that takes advantage of the electronic structure changes associated

with the triazole ring (Scheme 1).37

Scheme 1

Several of the coumarin-based fluorophore showed substantial increase in brightness

upon triazole formation, and could prove useful as biological probes. Key et al.38

have


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reported the triazole-substituted coumarin fluorophores 43 and 47 through CuAAC

reaction of coumarinyl alkyne (42, 46) and benzylazide. They also evaluated changes in

the photo-physical properties upon conversion from alkyne to triazole forms. Ethynyl-

coumarin structures showed increases in quantum yield (ca. 1.2 to 9 fold) and

bathochromic shifts (up to 23 nm) after triazole formation. Substitution of coumarin

fluorophores with azide or alkyne groups is known to induce changes in fluorescence

properties. Conjugation of an electron-donating triazole ring to the coumarin backbone at

one of the 3- or 7- positions causes an increase in quantum yield and a bathochromic shift

in emission relative to the starting alkyne.

Scheme 2


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Majumdar and Mandal39

have reported 1,2,3-triazolyl coumarin and quinolone

derivatives 50 through click reaction of coumarinyl on quinolone azide (48) with p-

substituted alkyne 49 by using CuI in DMSO (Scheme 3) and studied their fluorescence

properties. Coumarin and quinolone derivatives show good photo physical effects and

have a stable fluorescence property. Interestingly compounds 48 showed no fluorescence

property due to the quenching effect from electron-rich α- nitrogen of the azide group and

the compounds 50 exhibited high fluorescence due to elimination of the quenching

through the formation of the triazole ring.

Scheme 3

New fluorescent coumarin dyes were reported by Sivakumar et. al.40

Compound 54 was

synthesized with an azido group attached to the 3-position and then with catalytic

amount of Cu(I), the azide 54 reacted smoothly with phenylacetylene in a mixed solution

of ethanol and water (1:1) to afford cycloaddition products 55 at room temperature in

quantitative yield (Scheme 4). The fluorescent signals are triggered by the formation of

triazole ring, which has the potential to be used as probes for imaging or as reporters to

monitor the ligation efficiency. Compound 55 show fluorescence at 478 nm due to the

elimination of the quenching through the formation of the triazole ring. The quantum

yield of 55 is 0.30 in comparison to 0.0 of the starting materials 54.


13

Scheme 4

Gullapalli Kumaraswamy41

developed a novel and practical procedure for the synthesis

of small molecules possessing α-hydroxy or N-tosylamino 1,2,3-triazole motif 57a-e by

azidation of epoxides 56a-e or N-tosylaziridines with sodium azide followed by “click

reaction” using PEG-400 as a reaction medium in the presence of 5 mol % of CuI

(Scheme 5).

Scheme 5


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2.6. Present Work

Harmful infections caused by various fungal species, such as Aspergillus and Candida,

have been increasing throughout the world.42

Due to the increase in the number of

immune-compromised patients, such as cancer and HIV patients, primary and

opportunistic fungal infections are also mounting rapidly. Furthermore, resistance to the

existing antifungal agents is a growing problem. Almost all major classes of commercial

antibiotics have encountered resistance in clinical applications, even though the

pharmaceutical industry has produced a number of new antibiotics.43

Therefore, the need

for novel therapeutic agents with potency, a wide therapeutic window, and broad-

spectrum activity is critical.

The first generation of azoles antifungal inhibitors of CYP51, have revolutionized

treatment of some serious fungal infections. Triazoles have been the leading agents for

the control of fungal diseases of humans and animals for over last 20 years.44

According

to this, azole derivatives are currently the most widely studied class of antifungal agents.

The 1,2,3-triazole scaffold is very important in the field of medicinal chemistry and has

received much attention in the last few decades due to its chemotherapeutic value.45

1,2,3-Triazole and its derivatives are known to be potent anti-malarial,46

anticonvulsant,47

anti-bacterial,48

anti-fungal49

and anti-HIV agents.50

1,2,3-Triazole derivatives as GABA

receptor antagonists and potassium channel activators have also been demonstrated.51

Therefore, an investigation of the antimicrobial activity of another 1,2,3-triazole

derivative and an explanation of the structure-activity relationships for searching

clinically more valuable compounds would be worthwhile.

Coumarins (Benzopyran-2-ones) form an elite class of compounds, which occupy a

special role in nature and have been known both from synthetic and natural sources. It

was found to be crucial for a variety of pharmacological effects such as inhibition of

platelet aggregation52

, anti-inflammatory53

, anti-convulsant54

, anti-viral55

, anti-HIV56

,

anti-coagulant57

, anti-oxidant58

, anti-bacterial59

, anti-tubercular60

, anti-carcinogenic61

and

anti-fungal.62


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Discovery of efficient, scalable, ecological as well as economical synthesis for the

production of a library of clinical candidates is gaining importance. Copper (I) catalyzed

1,3-dipolar addition of azides to alkyne is one such chemical process which has placed

itself in a class of its own and has enabled many novel applications because of its

robustness.63

Using this clickable method for the synthesis of hybrid drugs is a promising

idea.

Therefore, in continuation of our longstanding interest in synthesis of new coumarin as

well as triazole derivatives, we have been prompted to synthesize new and possibly more

potential pharmacologically active compounds.The potential of triazole containing

coumarin derivatives as antifungal agents have not been studied yet. Therefore, the

current study was undertaken to synthesize a new series of triazolyl derivatives

containing a coumarin backbone with diversity at the 3- and 7- positions via. Huisgen

1,3-dipolar cycloaddition reaction. These compounds contain different alkyl chain at the

C-3 position of the coumarin ring and different aryl ethers at the C-4 position of

1,2,3,triazole ring. The antifungal potential of the synthesized compounds has been

investigated using Aspergillis as model pathogens.

A new series of 1,2,3-triazole substituted 3-alkyl-7-hydroxy-4-

methylcoumarinderivativeshave been synthesized via Cu(I)-catalyzed click chemistry on

7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarin with alkynes. The

synthesis of desired product was achieved starting from C-3 alkyl coumarins 62 and 63

which were synthesized via Pechman condensation of ethyl 2-ethylacetoacetate 60a and

ethyl 2-hexyl acetoacetate 60b with resorcinol (61) in 78 to 80 % yields (Scheme 7). The

2-ethyl/hexyl ethylacetoacetate in turn were prepared from ethyl acetoacetate (58) using

alkyl bromide 59a and 59b in THF in the presence of sodium hydride in 50 to 53 % yield,

respectively (Scheme 6). The C-3 alkyl substituted coumarins were condensed with

epichlorohydrin using 0.6 M NaOH solution in methanol to yield the corresponding

epoxides, 64 and 65 in 70 % yields. Further, the opening of the epoxy ring in compounds

64 and 65 using sodium azide in the presence of ammonium chloride in a methanol:water

(4:1) solution afforded 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarins 66

and 67 in 85 and 90 % yields (Scheme 7).


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Scheme 6: Alkylation of ethyl acetoacetate

Scheme 7: Synthesis of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-

methylcoumarins

Traditionally, the triazole forming 1,3-dipolar cycloaddition between azide and alkyne is

performed at high temperature & long duration that usually results in a mixture of two

isomers 1,4-disubstituted and 1,5-disubstituted 1,2,3-triazoles.64

Huisgen-Sharpless 1,3-


17

dipolar cycloaddition to form regioselectively 1, 4-disubstituted 1,2,3-triazole bridges is a

very popular and useful reaction for the bioconjugation.65

The reaction is regioselective

only in the presence of Cu (I) salts as a catalyst, because Cu (I) as a catalyst strongly

activated the terminal acetylenes towards 1,3-dipole in azide, to give the desired 1, 4-

disubstituted 1,2,3-triazole.

In the literature, Cu (I) catalysed cycloaddition was studied with various concentration of

CuSO4 in the presence of sodium ascorbate. And the reaction temperature along with

nature of solvent also influenced the CuAAC reaction. Using 0.05 molar equiv of CuSO4

in preliminary experiments, we observed the incomplete reaction. The reaction at 25-30

°C resulted in longer reaction time and moderate yields, while performing the reaction at

50 °C resulted in shorter reaction time and good yields. Hence, 50 °C was the optimum

temperature for the reaction. The yields of the desired 1,4-disubstituted 1,2,3-triazoles

were generally not significantly affected by the steric and electronic properties of the

groups attached to the alkynes reactive centers. So the best results were obtained by using

0.15 molar equiv. of CuSO4.5H2O in t-BuOH:H2O:THF in (1:1:1) ratio compared to t-

BuOH:H2O.

Thus, the Cu (I)-catalyzed process allowed the 1,3-dipolar cycloaddition of 7-(3-azido-2-

hydroxypropyloxy)-3-ethyl-hexyl-4-methylcoumarins 66/67 with commercially available

alkynes i. e. phenyl acetylene (68a), pent-4-ynioc acid (68b), 5-Chloro-1-pentyne (68c)

and propargyl alcohol (68e) in the presence of catalytic amount of copper sulphate and

sodium ascorbate in t-BuOH/H2O/THF (1:1:1) at 50 °C to afford 7-(3-(4-phenyl/alkyl-

1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarins 69a-d and

70a-d in 80 to 92 % yield (Schemes 8).


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Scheme 8: Synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-triazol-1-yl)propyloxy)-3-

ethyl-hexyl-4-methylcoumarins

Similarly, 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarins 66 and 67

were condensed with propargyl aryl ethers 72a-u in the presence of catalytic amount of

copper sulphate and sodium ascorbate in t-BuOH/H2O/THF (1:1:1) at 50 °C to afford

triazole containing coumarins 73a-u and 74a-u in 90 to 95 % yields (Schemes 9).

Propargyl aryl ethers 72a-u were prepared in excellent yield by heating substituted

phenols 71a-u with propargyl bromide and K2CO3 in acetone at 60 °C for 12 hr (Scheme

9).


19

Scheme 9: Synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-triazol-1-yl)propyloxy)-3-

ethyl/hexyl-4-methylcoumarins.


20

Thus, a series of fifty triazole containing coumarins 69a-d, 70a-d, 73a-u and 74a-u have

been synthesized together with the coumarin precursors 62, 63, 64, 65, 66 and 67. The

antifungal activity of fifty-two compounds, i. e. coumarins 66, 67, 69a-d, 70a-d, 73 a-u

and 74 a-u were evaluated against A. fumigatus, A. niger and A. flavus. The structures of

synthesized coumarin derivatives 62, 63, 64, 65, 66, 67, 69a-d, 70a-d, 73a-u and 74a-u

were unambiguously established by analysis of their spectral data (1H NMR,

13C NMR,

IR, HRMS spectra).Copies of the 1H- and

13C NMR spectrum of selected compounds are

given in the Results and Discussion section.

2.7. Results and Discussion

2.7.1 7-(3-Azido-2-hydroxypropyloxy)-3-ethyl-4-methycoumarin (66)

Compound 66 was synthesized by epoxide ring opening of

7-(2,3-epoxypropyloxy)-3-ethyl-4-methylcoumarin 64 with

sodium azide and ammonium chloride in methanol:water

solution at 70 oC and obtained as a white solid in 90 %

yield (Scheme 7). Its high resolution mass spectrum showed [M+Na]+

peak at m/z

326.1099 which confirmed its molecular formula to be C15H17N3O4. The absorption in the

IR spectrum at 2113 cm-1

was assigned to azide group present in the molecule. The

characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH & -OCH2 protons in its 1H NMR

spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.66 (2H, q, J = 7.3 Hz), 3.52-3.61 (2H,

m) and 4.07-4.27 (3H, m), respectively (Figure7). Similarly, in its 13

C NMR spectrum,

the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N3, -OCH2, -CH and CO appeared at

δ 13.03, 20.74, 53.27, 68.96, 69.36 and 161.94, respectively (Figure8). The peaks of all

other protons and carbons of the molecule were also present in the 1H and

13C NMR

spectra of the compound. Based on the spectral data analysis, the structure of the

compound was established as 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-

methylcoumarin (66).

2.7.2. 7-(3-Azido-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67)


21

Compound 67 was synthesized by epoxy ring opening

of 7-(2,3-epoxypropyloxy)-3-hexyl-4-methylcoumarin

65 with sodium azide and ammonium chloride in

methanol:water solution at 70 oC and obtained as a

white solid in 85 % yield (Scheme 7). Its high resolution mass spectrum showed [M+H]+

peak at m/z 360.1900 which confirmed its molecular formula to be C19H25N3O4. The

absorption in the IR spectrum at 2111 cm-1

was assigned to azide group present in the

molecule. The characteristic peak of -(CH2)5CH3, -CH2CH2(CH2)3CH3, -

CH2CH2(CH2)3CH3, -CH2(CH2)4CH3, -CH2N, -CH & -OCH2 protons in its 1H NMR

spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 1.30-1.40 (6H, m), 1.47-1.53 (2H, m),

2.63 (2H, t, J = 7.3 Hz) and 4.06-4.23 (3H, m), respectively (Figure9). Similarly, in its

13C NMR spectrum, the characteristic peaks for -(CH2)5CH3, -CH2(CH2)3CH2CH3, -

CH2CH2(CH2)2CH3, -(CH2)2CH2(CH2)2CH3, -(CH2)3CH2CH2CH3,-CH2N3, -OCH2, -CH

and CO appeared at δ 14.03, 22.57, 27.47, 29.31, 31.63, 53.26, 68.97, 69.35 and 162.07,

respectively (Figure 10). The peaks of all other protons and carbons of the molecule

were also present in the 1H and

13CNMR spectra of the compound. Based on the spectral

data analysis, the structure of the compound was established as 7-(3-azido-2-

hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67).

2.7.3. 3-Ethyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (69a)

Compound 69a was synthesized by click reaction of 7-(3-

azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin 66

and phenyl acetylene 68a in t-BuOH/H2O/THF (3 mL,

1/1/1) using sodium ascorbateand copper (II) sulfate

pentahydrate at 60 oC and obtained as a white solid in 85

% yield (Scheme 8). Its high resolution mass spectrum showed [M+H]+peak at m/z


IR spectrum at 3386 and 1708 cm-1

were assigned to OH and CO groups present in the

molecule. The characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ


22

and triazole H protons in its 1H NMRspectrum appeared at δ 1.04 (3H, t, J = 7.3 Hz),

2.57 (2H, q, J = 7.3 Hz), 4.08-4.16 (2H, m), 4.31-4.35 (1H, m), 4.48 (1H, dd, J = 10.3 Hz

& J = 7.3 Hz), 4.68 (1H, dd, J = 13.9 Hz & J = 3.7 Hz) and 8.57 (1H, s), respectively

(Figure 11). Similarly, in its 13

C NMR spectrum, the characteristic peaks for -CH2CH3,-

CH2CH3, -CH2N, -CH, -OCH2, and CO appeared at δ 12.97, 20.21, 52.71, 67.69, 70.09

and 160.75, respectively (Figure 12). The peaks of all other protons and carbons of the

molecule were also present in the 1H and

13CNMR spectra of the compound. Based on the

spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-

hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin(69a).

Figure 7:1H NMR spectrum of compound 66 (400 MHz, CDCl3)


23

Figure 8:13

C NMR spectrum of compound 66 (100.6 MHz, CDCl3)

Figure 9:1H NMR spectrum of compound 67 (400 MHz, CDCl3)


24

Figure 10:13

C NMR spectrum of compound 67 (100.6 MHz, CDCl3)

Figure 11:1H NMR spectrum of compound 69a (400 MHz, DMSO)


25

Figure 12:13

C NMR spectrum of compound 69a (100.6 MHz, DMSO)

2.7.4. 3-Ethyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-

methylcoumarin(69b)

Compound 69b was synthesized by click reaction of 7-

(3-azido-2-hydroxypropyloxy)-3-ethyl-4-

methylcoumarin 66 and pent-4-ynoic acid 68b in t-

BuOH/H2O/THF (3 mL, 1/1/1) using sodium ascorbate

and copper (II) sulfate pentahydrate at 60 oC and

obtained as white solid in 80 % yield (Scheme 8). Its high resolution mass spectrum

showed [M+H]+

peak at m/z 402.1656 which confirmed its molecular formula to be

C20H23N3O6. The absorption in the IR spectrum at 3461 and 1704 cm-1

were assigned to

OH and CO groups present in the molecule. The characteristic peak of -CH2CH3, -

CH2CH3 and -CH2CH2COOH, -CH2CH2COOH, -CH2N, -CH, -OCHα, -OCHβ and triazole

H protons in its 1H NMR spectrum appeared at δ 1.05 (3H, t, J = 7.7 Hz), 2.53-2.60 (4H,

m), 2.85 (2H, t, J = 7.3 Hz), 4.01-4.08 (2H, m), 4.20-4.26 (1H, m), 4.39 (1H, dd, J = 13.9


26

& 7.3 Hz), 4.55 (1H, dd, J = 13.9 & 3.6 Hz) and 7.85 (1H, s), respectively (Figure 13).

Similarly, in its 13

C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -

CH2CH2COOH, -CH2CH2COOH, -CH2N, -CH, -OCH2, CO and COOH appeared at δ

12.89, 20.15, 20.60, 33.09, 52.28, 67.65, 70.00, 160.69 and 173.58, respectively (Figure

14). The peaks of all other protons and carbons of the molecule were also present in the

1H and

13C NMR spectra of the compound. Based on the spectral data analysis, the

structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-propanoicacid)-

1,2,3-triazol-4-yl)propyoxl)-4-methylcoumarin (69b).

2.7.5. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl-4-

methylcoumarin (69c)

Compound 69c was synthesized by click reaction of

7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-

methylcoumarin 66 and 5-Chloro-1-pentyne 68c in t-

BuOH/H2O/THF (3 mL, 1/1/1) using sodium

ascorbate and copper (II) sulfate pentahydrate at 60

oC and obtained as a white solid in 88 % yield (Scheme 8). Its high resolution mass

spectrum showed [M+H]+

peak at m/z 406.1521 which confirmed its molecular formula

to be C20H24ClN3O4. The absorption in the IR spectrum at 3398 and 1713cm-1

were

assigned to OH and CO groups present in the molecule. The characteristic peak of -

CH2CH3, -CH2CH2CH2Cl, -CH2CH3, -CH2CH2CH2Cl, -CH2CH2CH2Cl, -CH2N, -CH, -

OCHα, -OCHβ and triazole H protons in its 1H NMR spectrum appeared at δ 1.05 (3H, t, J

= 7.3 Hz), 2.04 (2H, pentate), 2.56 (2H, q, J = 7.3 Hz), 2.75 (2H, t, J = 7.7 Hz), 3.67 (2H,

t, J = 6.9 Hz), 4.01-4.07 (2H, m), 4.20-4.26 (1H, m), 4.41 (1H, dd, J = 13.9 & 7.4 Hz),

4.56 (1H, dd, J = 13.9 & 3.6 Hz) and 7.89 (1H, s), respectively (Figure 15). Similarly, in

its 13

C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2CH2CH2Cl,

-CH2CH2CH2Cl, -CH2CH2CH2Cl, -CH2N, -CH,-OCH2, and CO appeared at δ 12.96,

20.20, 22.12, 31.79, 44.68, 52.34, 67.68, 70.07 and 160.72, respectively (Figure 16). The

peaks of all other protons and carbons of the molecule were also present in the 1H and

13C

NMR spectra of the compound. Based on the spectral data analysis, the structure of the


27

compound was established as 7-(3-(4-(3-chloropropyl)-1,2,3-triazol-1-yl)-2-

hydroxypropyloxy)-3-ethyl-4-methylcoumarin (69c).

2.7.6. 3-Ethyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (69d)

Compound 69d was synthesized by click reaction of 7-


methylcoumarin 66 and propargyl alcohol 68d in t-


ascorbate and copper (II) sulfate pentahydrate at 60 oC

and obtained as a white solid in 87 % yield (Scheme 8). Its high resolution mass

spectrum showed [M+Na]+


to be C18H21N3O5. The absorption in the IR spectrum at 3305 and 1676 cm-1

were


CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -CH2OH, -OCHβ and triazole H protons in its

1H NMR spectrum appeared at δ 0.96 (3H, t, J = 7.3 Hz), 2.47 (2H, q, J = 7.3 Hz), 3.92-

3.99 (2H, m), 4.13-4.20 (1H, m), 4.36 (1H, dd, J = 13.9 & 8.1 Hz), 4.43 (2H, d, J = 5.1

Hz), 4.49 (1H, dd, J = 13.9 & 3.7 Hz) and 7.86 (1H, s),respectively (Figure 17).



CH2N, -CH, -OCH2, and CO appeared at δ 12.99, 20.24, 52.33, 67.75, 70.09 and 160.79,



13C NMR spectra of the compound. Based on the spectral

data analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-

(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (69d).


28

Figure 13:1H NMR spectrum of compound 69b (400 MHz, DMSO)

Figure 14:13

C NMR of compound 69b (100.6 MHz, DMSO)


29

Figure 15:1H NMR spectrum of compound 69c (400 MHz, DMSO)

Figure 16:13

C NMR spectrum of compound 69c (100.6 MHz,DMSO)


30

Figure 17:1H NMR spectrum of compound 69d (400 MHz,DMSO)

Figure 18:13

C NMR spectrum of compound 69d (100.6 MHz,DMSO)


31

2.7.7. 3-Hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-


Compound 70a was synthesized by click reaction of

7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-

methylcoumarin 67 and phenylacetylene 68a in t-







were


(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in its 1H NMR spectrum

appeared at δ 0.86 (3H, t, J = 7.3 Hz), 4.07-4.14 (2H, m), 4.31-4.35 (1H, m), 4.50 (1H,

dd, J = 13.9 & 8.4 Hz), 4.68 (1H, dd, J = 13.9 & 3.6 Hz) and 8.57 (1H, s),respectively.


C NMR spectrum, the characteristic peaks for -(CH2)5CH3, -CH2N, -CH,

-OCH2 and CO appeared at δ 13.96, 52.70, 67.69, 70.09 and 160.75, respectively. The


13C


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (70a).

2.7.8. 3-Hexyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-

methylcoumarin (70b)

Compound 70b was synthesized by click reaction

of 7-(3-azido-2-hydroxypropyloxy)-3-hexyl-4-

methylcoumarin 67 and pent-4-ynoic acid 68b in

t-BuOH/H2O/THF (3 mL, 1/1/1) using sodium

ascorbate and copper (II) sulfate pentahydrate at

60 oC and obtained as a white solid in 79 % yield (Scheme 8). Its high resolution mass




were


32


(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in its1H NMRspectrum


dd, J = 13.9 &7.3 Hz), 4.55 (1H, dd, J = 13.9 &3.8 Hz) and 7.84 (1H, s), respectively


C NMR spectrum, the characteristic peaks for -(CH2)5CH3,

-CH2N, -CH, -OCH2 and CO appeared at δ 13.96, 52.36, 67.73, 70.09 and

160.93,respectively (Figure 20). The peaks of all other protons and carbons of the


13C NMR spectra of the compound. Based on

the spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-

hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-methylcoumarin (70b).

2.7.9. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-hexyl-4-


Compound 70c was synthesized by click

reaction of 7-(3-azido-2-hydroxypropyloxy)-3-

hexyl-4-methylcoumarin 67 and 5-Chloro-1-

pentyne 68c in t-BuOH/H2O/THF (3 mL,

1/1/1) using sodium ascorbateand copper (II)

sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 8). Its

high resolution mass spectrum showed [M+H]+peak at m/z 462.2157 which confirmed its

molecular formula to be C24H32ClN3O4. The absorption in the IR spectrum at 3398 and

1713 cm-1

were assigned to OH and CO groups present in the molecule. The

characteristicpeak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, and triazole H protons in

its1H NMRspectrum appeared at δ 0.84 (3H, t, J = 6.6 Hz), 3.96-4.05 (2H, m), 4.20-4.24

(1H, m), 4.38 (1H, dd, J = 13.9 &7.6 Hz), 4.55 (1H, dd, J = 13.9 &4.4 Hz) and 7.87 (1H,

s), respectively (Figure 21). Similarly, in its 13

C NMR spectrum, the characteristic peaks

for -(CH2)5CH3, -CH2N, -CH, -OCH2 and CO appeared at δ 13.96, 22.08, 22.29, 26.82,

28.20, 28.67, 31.13, 31.81, 44.69, 52.36, 67.71, 70.08 and 160.92,respectively (Figure


1H and

13CNMR spectra of the compound. Based on the spectral data analysis, the


33

structure of the compound was established as 7-(3-(4-(3-chloropropyl)-1,2,3-triazol-1-

yl)-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (70c).

2.7.10. 3-Hexyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-


Compound 70d was synthesized by click reaction of


methylcoumarin 67 and propargyl alcohol 68d in t-




spectrum showed [M+H]+peak at m/z 416.2176 which confirmed its molecular formula to

be C22H29N3O5. The absorption in the IR spectrum at 3385 and 1717 cm-1

were assigned

to OH and CO groups present in the molecule. The characteristicpeak of -(CH2)5CH3, -

CH2N, -CH, -OCHα, -CH2OH, -OCHβ, and triazole H protons in its1H NMRspectrum


dd, J = 13.9 &7.3 Hz), 4.52 (2H, d, J = 5.8 Hz ), 4.58 (1H, dd, J = 13.9 &3.8 Hz) and

7.95 (1H, s),respectively (Figure 23). Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2 and CO appeared at δ 12.99,

52.33, 67.75, 70.09 and 160.79,respectively (Figure 24). The peaks of all other protons

and carbons of the molecule were also present in the 1H and

13C NMR spectra of the

compound. Based on the spectral data analysis, the structure of the compound was

established as 3-hexyl-7-(2-hydroxy-3-(4-(hydroxymethyl)-1,2,3-triazol-1-yl)propyloxy)-

4-methylcoumarin (70d).


34

Figure 19:1H NMR spectrum of compound 70b (400 MHz,DMSO)

Figure 20:13

C NMR of compound 70b (100 MHz, DMSO)


35

Figure 21:1H NMR spectrum of compound 70c (400 MHz,DMSO)

Figure 22:13

C NMR spectrum of compound 70c (100 MHz,DMSO)


36

Figure 23:1H NMR spectrum of compound 70d (400 MHz,DMSO)

Figure 24:13

C NMR spectrum of compound 70d (100 MHz,DMSO)


37

2.7.11. 3-Ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-


Compound 73a was synthesized by click reaction of 7-


methylcoumarin 66 and 3-phenoxyprop-1-yne 72a in t-

BuOH/H2O/THF (3 mL, 1/1/1) using sodium ascorbate

and copper (II) sulfate pentahydrate at 60 oC and

obtained as a white solid in 85 % yield (Scheme 9). Its high resolution mass spectrum

showed [M+H]+

peak at m/z 436.1858 which confirmed its molecular formula to be

C24H25N3O5. The absorption in the IR spectrum at 3386 and 1717 cm-1

were assigned to

OH and CO groups present in the molecule. The characteristicpeak of -CH2CH3,-

CH2CH3, -CH2N, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ

1.10 (3H, t, J = 7.3 Hz), 2.62 (2H, q, J = 7.3 Hz), 4.01-4.05 (2H, m), 5.14 (2H, s) and

7.78 (1H, s), respectively. Similarly, in its 13


for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.03,

20.72, 52.99, 61.59, 68.29, 69.25 and 161.95, respectively. The peaks of all other protons




established as 3-ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (73a).

2.7.12. 3-Ethyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73b)

Compound 73b was synthesized by click reaction of 7-


methylcoumarin 66 and 1-Cl-2-(prope-2-yn-1-

yloxy)benzene 72b in t-BuOH/H2O/THF (3 mL, 1/1/1)

using sodium ascorbate and copper (II) sulfate

pentahydrate at 60 oC and obtained as a white solid in 92 % yield (Scheme 9). Its high

resolution mass spectrum showed [M+H]+

peak at m/z 470.1477 which confirmed its



38

1718 cm-1

were assigned to OH and COgroups present in the molecule. The characteristic

peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H

protons in its 1H NMR spectrum appeared at δ 1.13 (3H, t, J = 7.7 Hz), 2.65 (2H, q, J =

7.3 Hz), 4.03-4.09 (2H, m), 4.53-4.61 (2H, m), 4.74 (1H, dd, J = 13.9 & 3.8 Hz), 5.25

(2H, s) and 7.86 (1H, s),respectively (Figure 25). Similarly, in its 13

C NMR spectrum,

the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO

appeared at δ 13.03, 20.73, 53.02, 62.97, 68.30, 69.24 and 161.95, respectively (Figure


1H and


structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(2-

chlorophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73b).


yl)propyloxy)-4-methylcoumarin (73c)

Compound 73c was synthesized by click reaction of

7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-


yloxy)benzene 72c in t-BuOH/H2O/THF (3 mL,

1/1/1) using sodium ascorbate and copper (II)




1706 cm-1


characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and

triazole H protons in its1H NMR spectrum appeared at δ 1.08 (3H, t, J = 7.3 Hz), 2.62

(2H, q, J = 7.3 Hz), 4.01-4.06 (2H, m), 4.50-4.60 (2H, m), 4.71 (1H, dd, J = 13.9 & 3.8

Hz), 5.13 (2H, s) and 7.79 (1H, s), respectively (Figure 27). Similarly, in its 13

C NMR

spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -

OCH2, and CO appeared at δ 13.03, 20.74, 53.00, 61.87, 68.32, 69.26 and 161.94,





39


(4-((3-chlorophenoxy) methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73c).


yl)propyloxy)-4-methylcoumarin (73d)




yloxy)benzene 72d in t-BuOH/H2O/THF (3 mL,

1/1/1) using sodium ascorbate and copper (II) sulfate





1718 cm-1


characteristicpeak of -CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and


(2H, q, J = 7.3 Hz), 4.03-4.11 (2H, m), 4.51-4.60 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.2


C NMR





13C spectra of the compound. Based on the spectral data

analysis, the structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(4-

chlorophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73d).


40

Figure 25:1H NMR spectrum of compound 73b (400 MHz, CDCl3)

Figure 26:13

C NMR spectrum of compound 73b (100.6 MHz, CDCl3)


41

Figure 27:1H NMR spectrum of compound 73c (400 MHz, CDCl3)

Figure 28:13

C NMR spectrum of compound 73c (100.6 MHz, CDCl3)


42

Figure 29:1H NMR spectrum of compound 73d (400 MHz, CDCl3)

Figure 30:13

C NMR spectrum of compound 73d (100.6 MHz, CDCl3)


43

2.7.15. 3-Ethyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73e)

Compound 73e was synthesized by click reaction of 7-

(3-azido-2-hydroxypropyloxy)-3ethyl-4-

methylcoumarin 66 and 1-Br-2-(prope-2-yn-1-

yloxy)benzene 72e in t-BuOH/H2O/THF (3 mL, 1/1/1)





molecular formula to be C24H24BrN3O5. The absorption in the IR spectrum at 3246 and

1710 cm-1



triazole H protons in its 1H NMR spectrum appeared at δ 1.14 (3H, t, J = 7.3 Hz), 2.65

(2H, q, J = 8.1 Hz), 4.03-4.09 (2H, m), 4.51-4.61 (2H, m), 4.73 (1H, dd, J = 13.9 & 2.2


C NMR







bromophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73e).

2.7.16. 3-Ethyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73f)

Compound 73f was synthesized by click reaction of



yloxy)benzene 72f in t-BuOH/H2O/THF (3 mL,




44




1717 cm-1




(2H, q, J = 7.3 Hz), 4.03-4.10 (2H, m), 4.51-4.60 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.9


C NMR







(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73f).

Figure 31:1H NMR spectrum of compound 73e (400 MHz, CDCl3)


45

Figure 32:13

C NMR spectrum of compound 73e (100.6 MHz, CDCl3)

Figure 33:1H NMR spectrum of compound 73f (400 MHz, CDCl3)


46

Figure 34:13

C NMR spectrum of compound 73f (100.6 MHz, CDCl3)

2.7.17. 3-Ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73g)

Compound 73g was synthesized by click reaction of 7-


methylcoumarin 66 and 1-nitro-2-(prope-2-yn-1-

yloxy)benzene 72g in t-BuOH/H2O/THF (3 mL, 1/1/1)





molecular formula to be C24H24N4O7. The absorption in the IR spectrum at 3419 and

1689 cm-1


characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and


(2H, q, J = 7.2 Hz), 4.01-4.10 (2H, m), 4.22-4.28 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3


47

Hz), 4.62 (1H, dd, J = 13.9 Hz & J = 3.8 Hz), 5.36 (2H, s) and 8.22 (1H, s), respectively



CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 12.89, 20.14, 52.49,

62.48, 67.53, 69.98 and 160.69, respectively (Figure 36). The peaks of all other protons




established as 3-ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73g).


yl)propyloxy)-4-methylcoumarin (73h)

Compound 73h was synthesized by click reaction

of 7-(3-azido-2-hydroxypropyloxy)-3ethyl-4-


yloxy)benzene 72h in t-BuOH/H2O/THF (3 mL,



high resolution mass spectrum showed [M+H]+



1716 cm-1


characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH and-OCHα, -OCHβ, -CH2OPh and


(2H, q, J = 7.3 Hz), 4.00-4.10 (2H, m), 4.50-4.62 (2H, m), 4.75 (1H, dd, J = 13.8 & 3.2

Hz), 5.28 (2H, s) and 7.86 (1H, m), respectively (Figure 37). Similarly, in its 13

C NMR

spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph,- CH, -






(4-(3-nitrophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73h).


48


yl)propyloxy)-4-methylcoumarin (73i)

Compound 73i was synthesized by click reaction of



yloxy)benzene 72i in t-BuOH/H2O/THF (3 mL,






1699 cm-1


characteristic peak of -CH2CH3, -CH2CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and


(2H, q, J = 7.3 Hz), 4.00-4.10 (2H, m), 4.22-4.29 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3

Hz), ), 4.63 (1H, dd, J = 13.9 & 3.8 Hz), 5.33 (2H, s) and 8.27 (1H, s), respectively



CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 12.88, 20.15, 52.51,



13CNMR spectra of the


established as 3-ethyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73i).


49

Figure 35:1H NMR spectrum of compound 73g (400 MHz, DMSO)

Figure 36:13

C NMR spectrum of compound 73g (100.6 MHz, DMSO)


50

Figure 37:1H NMR spectrum of compound 73h (400 MHz,DMSO)

Figure 38:13

C NMR spectrum of compound 73h (100.6 MHz, DMSO)


51

Figure 39:1H NMR spectrum of compound 73i (400 MHz, DMSO)

Figure 40:13

C NMR spectrum of compound 73i (100.6 MHz, DMSO)


52

2.7.20. 3-Ethyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (73j)

Compound 73j was synthesized by click reaction of 7-


methylcoumarin 66 and 1-methyl-2-(prope-2-yn-1-

yloxy)benzene 72j in t-BuOH/H2O/THF (3 mL, 1/1/1)






1716 cm-1


characteristic peak of -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -

CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 1.15 (3H, t, J =

8.1 Hz), 2.28 (1H, s), 2.63 (2H, q, J = 8.1 Hz), 4.03-4.6 (2H, m), 4.47-4.57 (2H, m), 4.70

(1H, dd, J = 13.9 & 3.8 Hz), 5.14 (2H, s) and 7.77 (1H, s), respectively. Similarly, in its

13C NMR spectrum, the characteristic peaks for -CH2CH3, Ph-CH3, -CH2CH3, -CH2N, -

OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.02, 14.48, 20.15, 52.94, 61.99, 68.32,

69.25 and 161.93, respectively. The peaks of all other protons and carbons of the



the spectral data analysis, the structure of the compound was established as 3-ethyl-7-(2-

hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73j).

2.7.21. 3-Ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-

4-methylcoumarin (73k)

Compound 73k was synthesized by click reaction


methylcoumarin 66 and 1-methyl-3-(prope-2-yn-

1-yloxy)benzene 72k in t-BuOH/H2O/THF (3

mL, 1/1/1) using sodium ascorbate and copper

(II) sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 9).

Its high resolution mass spectrum showed [M+H]+

peak at m/z 450.2023 which confirmed


53

its molecular formula to be C25H27N3O5. The absorption in the IR spectrum at 3511 and

1718 cm-1



CH2OPh and triazole H protons in its1H NMR spectrum appeared at δ 1.12 (3H, t, J = 7.4

Hz), 2.17 (1H, s), 2.64 (2H, q, J = 8.1 Hz), 4.0-4.08 (2H, m), 4.48-4.60 (2H, m), 4.72

(1H, dd, J = 13.9 & 3.8 Hz), 5.18 (2H, s) and 7.75 (1H, s), respectively (Figure 41).


C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, Ph-

CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.02, 20.72, 21.42, 53.00,





established as 3-ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73k).

2.7.22. 3-Ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-3-

ethyl-4-methylcoumarin (73l)

Compound 73l was synthesized by click reaction



yloxy)benzene 72l in t-BuOH/H2O/THF (3 mL,






1721 cm-1




7.3 Hz), 2.26 (1H, s), 2.64 (2H, q, J = 7.3 Hz), 4.01-4.08 (2H, m), 4.51-4.57 (2H, m),

4.72 (1H, dd, J = 13.9 &3.7 Hz), 5.13 (2H, s) and 7.78 (1H, s), respectively (Figure 43).


C NMR spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, Ph-


54

CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.08, 20.45, 20.79, 52.91,





established as 3-ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin(73l).

Figure 41:1H NMR spectrum of compound 73k (400 MHz, CDCl3)


55

Figure 42:13

C NMR spectrum of compound 73k (100.6 MHz, CDCl3)

Figure 43:1H NMR spectrum of compound 73l (400 MHz, CDCl3)


56

Figure 44:13

C NMR spectrum of compound 73l (100.6 MHz, CDCl3)

2.7.23. 3-Ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73m)

Compound 73m was synthesized by click reaction of


methylcoumarin 66 and 1-methoxy-2-(prope-2-yn-1-

yloxy)benzene 72m in t-BuOH/H2O/THF (3 mL,






1674 cm-1


characteristic peak of -CH2CH3, -CH2CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -OCHβ, -


7.7 Hz), 2.62 (2H, q, J = 8.1 Hz), 3.80 (1H, m), 4.01-4.05 (2H, m), 4.45-4.54 (2H, m),


57

4.68 (1H, dd, J = 11.9 & 2.9 Hz), 5.23 (2H, s) and 7.80 (1H, s), respectively (Figure 45).



CH2N, Ph-OCH3, -OCH2Ph, -CH, -OCH2, and CO appeared at δ 13.03, 20.74, 52.94,

55.72, 62.82, 68.36, 69.22 and 161.91, respectively (Figure 46). The peaks of all other

protons and carbons of the molecule were also present in the 1H and

13C NMR spectra of

the compound. Based on the spectral data analysis, the structure of the compound was

established as 3-ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73m).

2.7.24. 3-Ethyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73n)

Compound 73n was synthesized by click reaction


methylcoumarin 66 and 1-methoxy-3-(prope-2-

yn-1-yloxy)benzene 72n in t-BuOH/H2O/THF (3

mL, 1/1/1) using sodium ascorbate and copper

(II) sulfate pentahydrate at 60 oC and obtained as a white solid in 86 % yield (Scheme 9).




1708 cm-1


characteristic peak of -CH2CH3, -CH2CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -OCHβ, -


7.32 Hz), 2.65 (2H, q, J = 7.32 Hz), 3.77 (1H, m), 4.03-4.10 (2H, m), 4.50-4.59 (2H, m),

4.72 (1H, dd, J = 12.4 & 2.2 Hz), 5.16 (2H, s) and 7.80 (1H, s), respectively (Figure 47).



CH2N, Ph-OCH3, -CH, -OCH2 and CO appeared at δ 13.04, 20.75, 52.98, 55.21, 68.36,

69.25 and 161.94, respectively (Figure 48). The peaks of all other protons and carbons of

the molecule were also present in the 1H and

13C NMR spectra of the compound. Based

on the spectral data analysis, the structure of the compound was established as 3-ethyl-7-

(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (73n).


58

2.7.25. 3-Ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73o)

Compound 73o was synthesized by click reaction of 7-


methylcoumarin 66 and 1-iodo-2-(prope-2-yn-1-

yloxy)benzene 72o in t-BuOH/H2O/THF (3 mL, 1/1/1)





molecular formula to be C24H24IN3O5. The absorption in the IR spectrum at 3273 and

1711 cm-1




(2H, q, J = 7.3 Hz), 4.03-4.08 (2H, m), 4.52-4.63 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9

Hz), 5.25 (2H, s) and 7.89 (1H, s), respectively. Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO

appeared at δ 13.05, 20.77, 53.00, 63.39, 68.39, 69.19 and 161.92, respectively. The

peaks of all the protons and carbons of the molecule were also present in the 1H and

13C


compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxy methyl)-1,2,3-

triazol-1-yl)propyloxy)-4-methylcoumarin (73o).

2.7.26. 3-Ethyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73p)

Compound 73p was synthesized by click reaction of



yloxy)benzene 72p in t-BuOH/H2O/THF (3 mL,






59


1715 cm-1




(2H, q, J = 7.3 Hz), 4.00-4.08 (2H, m), 4.49-4.57 (2H, m), 4.71 (1H, dd, J = 13.2 & 3.7


C NMR







(4-(4-iodophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73p).

Figure 45:1H NMR spectrum of compound 73m (400 MHz, CDCl3)


60

Figure 46:13

C NMR spectrum of compound 73m (100.6 MHz, CDCl3)

Figure 47:1H NMR spectrum of compound 73n (400 MHz, CDCl3)


61

Figure 48:13

C NMR spectrum of compound 73n (100.6 MHz, CDCl3)

Figure 49:1H NMR spectrum of compound 73p (400 MHz, CDCl3)


62

Figure 50:13

C NMR spectrum of compound 73p (100.6 MHz, CDCl3)

2.7.27. 3-Ethyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73q)

Compound 73q was synthesized by click reaction of


methylcoumarin 66 and 1-fluoro-3-(prope-2-yn-1-

yloxy)benzene 72q in t-BuOH/H2O/THF (3 mL,





molecular formula to be C24H24FN3O5. The absorption in the IR spectrum at 3392 and

1706 cm-1




(2H, q, J = 7.3 Hz), 4.00-4.07 (2H, m), 4.48-4.58 (2H, m), 4.71 (1H, dd, J = 13.2 & 2.9


C NMR


63







(4-(3-fluorophenoxy methyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73q).

2.7.28. 3-Ethyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73r)

Compound 73r was synthesized by click reaction of


methylcoumarin 66 and 1-fluoro-3-(prope-2-yn-1-

yloxy)benzene 72r in t-BuOH/H2O/THF (3 mL,






1705 cm-1




(2H, q, J = 7.4 Hz), 4.02-4.10 (2H, m), 4.52-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9


C NMR



respectively (Figure 54). The peaks of all the protons and carbons of the molecule were

also present in the 1H and



fluorophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73r).


64

Figure 51:1H NMR spectrum of compound 73q (400 MHz, CDCl3)

Figure 52:13

C NMR spectrum of compound 73q (100.6 MHz, CDCl3)


65

Figure 53:1H NMR spectrum of compound 73r (400 MHz, CDCl3)

Figure 54:13

C NMR spectrum of compound 73r (100.6 MHz, CDCl3)


66

2.7.29. 3-Ethyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73s)

Compound 73s was synthesized by click reaction of 7-


methylcoumarin 66 and 4-(prope-2-yn-1-yloxy)-1,1'-

biphenyl 72s in t-BuOH/H2O/THF (3 mL, 1/1/1) using

sodium ascorbate and copper (II) sulfate pentahydrate

at 60 oC and obtained as a white solid in 89 % yield (Scheme 9). Its high resolution mass




were


CH2CH3, -CH2CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H protons in

its 1H NMR spectrum appeared at δ 1.10 (3H, t, J = 7.6 Hz), 2.62 (2H, q, J = 7.3 Hz),

4.00-4.08 (2H, m), 4.50-4.58 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.21 (2H, s) and

7.80 (1H, s), respectively (Figure 55). Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -OCH2Ph, -CH, -OCH2, and CO

appeared at δ 13.02, 20.72, 53.03, 61.75, 68.31, 69.28 and 161.93, respectively (Figure


1H and


structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(4-

phenylphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73s).

2.7.30. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73t)

Compound 73t was synthesized by click reaction of


methylcoumarin 66 and 2-(prope-2-yn-1-

yloxy)naphthalene 72t in t-BuOH/H2O/THF (3 mL,






67


1718 cm-1



triazole H protons in its 1H NMRspectrum appeared at δ 1.11 (3H, t, J = 7.3 Hz), 2.62

(2H, q, J = 7.3 Hz), 4.00-4.07 (2H, m), 4.48-4.57 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8


C NMR

spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -CH,-OCH2, -OCH2Ph

and CO appeared at δ 13.02, 20.72, 53.03, 61.66, 68.31, 69.27 and 161.93,respectively

(Figure 58). The peaks of all other protons and carbons of the molecule were also present

in the 1H and


structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-

yloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73t).

Figure 55:1H NMR spectrum of compound 73s (400 MHz, CDCl3)


68

Figure 56:13

C NMR spectrum of compound 73s (100.6 MHz, CDCl3)

Figure 57:1H NMR spectrum of compound 73t (400 MHz, CDCl3)


69

Figure 58:13

C NMR spectrum of compound 73t (100.6 MHz, CDCl3)

2.7.31. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73u)

Compound 73u was synthesized by click reaction of


methylcoumarin 66 and 1-(prope-2-yn-1-

yloxy)naphthalene 72u in t-BuOH/H2O/THF (3 mL,






1698 cm-1




(2H, q, J = 7.3 Hz), 3.99-4.06 (2H, m), 4.52-4.57 (2H, m), 4.70 (1H, dd, J = 13.9 &3.7


C NMR


70

spectrum, the characteristic peaks for -CH2CH3, -CH2CH3, -CH2N, -CH, -OCH2, -OCH2Ph

and CO appeared at δ 13.02, 20.72, 53.01, 62.07, 68.32, 69.25 and 161.95, respectively


in the 1H and


structure of the compound was established as 3-ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-

yloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (73u).

2.7.32. 3-Hexyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-


Compound 74a was synthesized by click reaction


methylcoumarin 67 and 3-phenoxyprop-1-yne 72a

in t-BuOH/H2O/THF (3 mL, 1/1/1) using sodium

ascorbate and copper (II) sulfate pentahydrate at

60 oC and obtained as a white solid in 85 % yield (Scheme 9). Its high resolution mass




were


(CH2)5CH3, -CH2N, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at

δ 0.89 (3H, t, J = 7.3 Hz), 4.02-4.09 (2H, m), 5.19 (2H, s), and 7.79 (1H, s), respectively



-CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 13.96, 52.99, 61.59, 68.29, 69.24

and 161.95, respectively (Figure 62). The peaks of all other protons and carbons of the



the spectral data analysis, the structure of the compound was established as 3-hexyl-7-(2-

hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74a).


71

Figure 59:1H NMR spectrum of compound 73u (400 MHz, CDCl3)

Figure 60:13

C NMR spectrum of compound 73u (100.6 MHz, CDCl3)


72

Figure 61:1H NMR spectrum of compound 74a (400 MHz, CDCl3)

Figure 62:13

C NMR spectrum of compound 74a (100.6 MHz, CDCl3)


73

2.7.33. 3-Hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-


Compound 74b was synthesized by click reaction



yloxy)benzene 72b in t-BuOH/H2O/THF (3 mL,






1718 cm-1


characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole


m), 4.52-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.2 Hz), 5.26 (2H, s), and 7.85 (1H, s),

respectively (Figure 63). Similarly, in its 13

C NMR spectrum, the characteristic peaks for

-(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 12.99, 53.02, 62.97,

68.30, 69.24 and 161.95, respectively (Figure 64). The peaks of all other protons and

carbons of the molecule were also present in the 1H and



established as 3-hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74b).



Compound 74c was synthesized by click


hexyl-4-methylcoumarin 67 and 1-Cl-3-(prope-

2-yn-1-yloxy)benzene 72c in t-


ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as a white solid in 85


74

% yield (Scheme 9). Its high resolution mass spectrum showed [M+H]+

peak at m/z

526.2106 which confirmed its molecular formula to be C28H32ClN3O5. The absorption in

the IR spectrum at 3393 and 1705 cm-1

were assigned to OH and CO groups present in

the molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -


6.6 Hz), 4.03-4.09 (2H, m), 4.53-4.60 (2H, m), 4.73 (1H, dd, J = 13.9 & 3.7 Hz), 5.16

(2H, s), and 7.81 (1H, s), respectively (Figure 65). Similarly, in its 13

C NMR spectrum,

the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared

at δ 12.99, 53.00, 61.87, 68.32, 69.26 and 161.94, respectively (Figure 66). The peaks of

all other protons and carbons of the molecule were also present in the 1H and

13C NMR


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-chlorophenoxymethyl)-

1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74c).






yloxy)benzene 72d in t-BuOH/H2O/THF (3 mL,






1718 cm-1


characteristicpeak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole

H protons in its1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 4.02-4.10 (2H,









75


established as 3-hexyl-7-(2-hydroxy-3-(4-(4-chlorophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74d).

Figure 63:1H NMR spectrum of compound 74b (400 MHz, CDCl3)


76

Figure 64:13

C NMR spectrum of compound 74b (100.6 MHz, CDCl3)

Figure 65:1H NMR spectrum of compound 74c (400 MHz, CDCl3)


77

Figure 66:13

C NMR spectrum of compound 74c (100.6 MHz, CDCl3)

Figure 67:1H NMR spectrum of compound 74d (400 MHz, CDCl3)


78

Figure 68:13

C NMR spectrum of compound 74d (100.6 MHz, CDCl3)

2.7.36. 3-Hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-


Compound 74e was synthesized by click reaction



yloxy)benzene 72e in t-BuOH/H2O/THF (3 mL,

1/1/1, v/v/v) using sodium ascorbate and copper

(II) sulfate pentahydrate at 60oC and obtained as a white solid in 91% yield (Scheme 9).



its molecular formula to be C28H32BrN3O5. The absorption in the IR spectrum at 3232

and 1718 cm-1






79








established as 3-hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74e).

2.7.37. 3-Hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-


Compound 74f was synthesized by click reaction of



yloxy)benzene 72f in t-BuOH/H2O/THF (3 mL,






1717 cm-1


characteristicpeak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole

H protons in its1H NMR spectrum appeared at δ 0.89 (3H, t, J = 7.3 Hz), 4.02-4.09 (2H,

m), 4.50-4.59 (2H, m), 4.74 (1H, dd, J = 13.9 & 2.9 Hz), 5.15 (2H, s), and 7.80 (1H, s)

,respectively (Figure 71). Similarly, in its 13


for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.03, 53.01,





established as 3-hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74f).


80

Figure 69:1H NMR spectrum of compound 74e (400 MHz, CDCl3)

Figure 70:13

C NMR spectrum of compound 74e (100.6 MHz, CDCl3)


81

Figure 71:1H NMR spectrum of compound 74f (400 MHz, CDCl3)

Figure 72: 13

C NMR spectrumof compound 74f(100.6 MHz, CDCl3)


82

2.7.38. 3-Hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-


Compound 74g was synthesized by click reaction



yloxy)benzene 72g in t-BuOH/H2O/THF (3 mL,




peak at m/ z 537.2346 which confirmed


1716 cm-1


characteristic peak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and triazole H

protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz), 4.01-4.10 (2H,

m), 4.22-4.30 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3 Hz), 4.60 (1H, dd, J = 13.9 & 3.7

Hz), 5.35 (2H, s), and 8.21 (1H, s), respectively. Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at

δ 14.01, 52.49, 62.58, 67.67, 70.10 and 160.67,respectively. The peaks of all other

protons and carbons of the molecule were also present in the 1H and

13C NMR spectra of

the compound. Based on the spectral data analysis, the structure of the compound was

established as 3-hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74g).



Compound 74h was synthesized by click


hexyl-4-methylcoumarin 67 and 1-nitro-3-

(prope-2-yn-1-yloxy)benzene 72h in t-


ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as a white solid in 88


83





molecule. The characteristicpeak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh

and triazole H protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz),

3.99-4.07 (2H, m), 4.21-4.28 (1H, m), 4.45 (1H, dd, J = 13.2 & 3.7 Hz), 4.61 (1H, dd, J =

13.8 & 3.2 Hz), 5.29 (2H, s), and 8.25 (1H, s), respectively. Similarly, in its 13

C NMR

spectrum, the characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2 -CH2OPh and CO

appeared at δ 14.62, 52.54, 61.76, 67.61, 70.06 and 160.67,respectively. The peaks of all

other protons and carbons of the molecule were also present in the 1H and

13C NMR


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-nitrophenoxymethyl)-1,2,3-

triazol-1-yl)propyloxy)-4-methylcoumarin (74h).



Compound 74i was synthesized by click reaction of



yloxy)benzene 72i in t-BuOH/H2O/THF (3 mL,


sulfate pentahydrate at 60 oC and obtained as white solid in 86 % yield (Scheme 9). Its




1699 cm-1


characteristic peak of -(CH2)5CH3, -CH2N, -CH, -OCHα, -OCHβ, -CH2OPh and triazole H

protons in its 1H NMR spectrum appeared at δ 0.84 (3H, t, J = 7.3 Hz), 4.00-4.07 (2H,

m), 4.22-4.28 (1H, m), 4.48 (1H, dd, J = 13.9 & 7.3 Hz), 4.63 (1H, dd, J = 13.9 & 3.7

Hz), 5.32 (2H, s), and 8.27 (1H, s), respectively. Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ

13.95, 52.58, 61.91, 67.61, 70.07 and 163.23, respectively. The peaks of all the protons


13C spectra of the compound.


84

Based on the spectral data analysis, the structure of the compound was established as 3-

hexyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (74i).

2.7.41. 3-Hexyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (74j)

Compound 74j was synthesized by click reaction

of 7-(3-azido-2-hydroxypropyloxy)-hexyl-4-

methylcoumarin 67 and 1-methyl-2-(prope-2-yn-

1-yloxy)benzene 72j in t-BuOH/H2O/THF (3 mL,






1716 cm-1


characteristic peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh


2.18 (1H, s), 4.05-4.09 (2H, m), 4.54-4.60 (2H, m), 4.71 (1H, dd, J = 13.9 & 3.7 Hz),

5.19 (2H, s), and 7.78 (1H, s), respectively (Figure 73). Similarly, in its 13

C NMR

spectrum, the characteristic peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -

CH2OPh and CO appeared at δ 14.04, 52.94, 62.03, 68.32, 69.26 and 161.93,respectively


in the 1H and


structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(o-

tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74j).

2.7.42. 3-Hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-

4-methylcoumarin (74k)


85

Compound 74k was synthesized by click reaction



yloxy)benzene 72k in t-BuOH/H2O/THF (3 mL,






1718 cm-1

were assigned to OH and CO group present in the molecule. The characteristic

peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh and triazole H

protons in its 1H NMR spectrum appeared at δ 0.88 (3H, t, J = 7.3 Hz), 2.31 (1H, s), 4.03-

4.09 (2H, m), 4.53-4.58 (2H, m), 4.72 (1H, dd, J = 13.9 & 3.7 Hz), 5.16 (2H, s), and 7.79

(1H, s), respectively (Figure 75). Similarly, in its 13

C NMR spectrum, the characteristic

peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ

14.03, 21.44, 53.01, 61.59, 68.32, 69.26 and 161.93, respectively (Figure 76). The peaks

of all other protons and carbons of the molecule were also present in the 1H and

13C NMR


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-

triazol-1-yl)propyloxy)-4-methylcoumarin (74k).

2.7.43. 3-Hexyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-

methylcoumarin (74l)

Compound 74l was synthesized by click reaction of



yloxy)benzene 72l in t-BuOH/H2O/THF (3 mL,







86

1721 cm-1


characteristic peak of -(CH2)5CH3, Ph-CH3, -CH2N, -CH and -OCHα, -OCHβ, -CH2OPh


2.27 (1H, s), 4.03-4.10 (2H, m), 4.49-4.58 (2H, m), 4.72 (1H, dd, J = 13.9 & 3.7 Hz),

5.14 (2H, s) and 7.79 (1H, s), respectively (Figure 77). Similarly, in its 13

C NMR

spectrum, the characteristic peaks for -(CH2)5CH3, Ph-CH3, -CH2N, -CH, -OCH2, -

CH2OPh and CO appeared at δ 14.04, 20.41, 52.97, 61.85, 68.39, 69.25 and 162.21,




data analysis, the structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-

(4-(p-tolyloxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74l).

Figure 73:1H NMR spectrum of compound 74j (400 MHz, CDCl3)


87

Figure 74:13

C NMR spectrum of compound 74j (100.6 MHz, CDCl3)

Figure 75:1H NMR spectrum of compound 74k (400 MHz, CDCl3)


88

Figure 76:13

C NMR spectrum of compound 74k (100.6 MHz, CDCl3)

Figure 77:1H NMR spectrum of compound 74l (400 MHz, CDCl3)


89

Figure 78:13

C NMR spectrum of compound 74l (100.6 MHz, CDCl3)

2.7.44. 3-Hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74m)

Compound 74m was synthesized by click


hexyl-4-methylcoumarin 67 and 1-methoxy-2-

(prope-2-yn-1-yloxy)benzene 72m in t-


ascorbate and copper (II) sulfate pentahydrate at 60 oC and obtained as white solid in 83


peak at m/z




molecule. The characteristicpeak of -(CH2)5CH3, Ph-OCH3, -CH2N, -CH and -OCHα, -

OCHβ, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.89 (3H,


90

t, J = 7.3 Hz), 4.00-4.05 (2H, m), 4.45-4.55 (2H, m), 4.69 (1H, dd, J = 11.9 & 2.9 Hz),

5.26 (2H, s), and 7.83 (1H, s), respectively. Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -(CH2)5CH3, -CH2N, Ph-OCH3, -CH, -OCH2, -CH2OPh and CO



13C


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-

1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74m).

2.7.45. 3-Hexyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74n)

Compound 74n was synthesized by click


hexyl-4-methylcoumarin 67 and 1-methoxy-3-

(prope-2-yn-1-yloxy)benzene 72n in t-




peak at m/z



were assigned to OH and CO group present in the

molecule. The characteristic peak of -(CH2)5CH3, Ph-OCH3 -CH2N, -CH and -OCHα, -

OCHβ, -CH2OPh and triazole H protons in its 1H NMR spectrum appeared at δ 0.88 (3H,

t, J = 7.3 Hz), 4.03-4.10 (2H, m), 4.53-4.59 (2H, m), 4.72 (1H, dd, J = 12.4 & 2.2 Hz),

5.16 (2H, s) and 7.80 (1H, s), respectively. Similarly, in its 13

C NMR spectrum, the

characteristic peaks for -(CH2)5CH3, -CH2N, Ph-OCH3, -CH, -OCH2, -CH2OPh and CO



13C


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-

1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74n).


91

2.7.46. 3-Hexyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-


Compound 74o was synthesized by click reaction



yloxy)benzene 72o in t-BuOH/H2O/THF (3 mL,





1717 cm-1




m), 4.54-4.63 (2H, m), 4.72 (1H, dd, J = 13.2 & 2.9 Hz), 5.24 (2H, s) and 7.89 (1H, s),




68.39, 69.15 and 161.94 ,respectively (Figure 80). The peaks of all other protons and




established as 3-hexyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74o).

2.7.47. 3-Hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin 714p)

Compound 74p was synthesized by click reaction of



yloxy)benzene 72p in t-BuOH/H2O/THF (3 mL,


pentahydrate at 60 oC and obtained as white solid in 85 % yield (Scheme 9). Its high


92




1715 cm-1












established as 3-hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74p).

Figure 79:1H NMR spectrum of compound 74o (400 MHz, CDCl3)


93

Figure 80:13

C NMR spectrum of compound 74o (100.6 MHz, CDCl3)

Figure 81:1H NMR spectrum of compound 74p (400 MHz, CDCl3)


94

Figure 82:13

C NMR spectrum of compound 74p (100.6 MHz, CDCl3)

2.7.48. 3-Hexyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-


Compound 74q was synthesized by click reaction


methylcoumarin 67 and 1-flouro-3-(prope-2-yn-1-

yloxy)benzene 72q in t-BuOH/H2O/THF (3 mL,






1702 cm-1




m), 4.48-4.58 (2H, m), 4.71 (1H, dd, J = 13.2 & 2.9 Hz), 5.16 (2H, s) and 7.82 (1H,


95

s),respectively. Similarly, in its 13

C NMR spectrum, the characteristic peaks for -

(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.05, 52.97, 61.96,

68.39, 69.23 and 164.65, respectively. The peaks of all other protons and carbons of the




hydroxy-3-(4-(3-flourophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin

(74q).

2.7.49. 3-Hexyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-


Compound 74r was synthesized by click reaction of


methylcoumarin 67 and 1-flouro-4-(prope-2-yn-1-

yloxy)benzene 72r in t-BuOH/H2O/THF (3 mL,






1702 cm-1




m), 4.50-4.60 (2H, m), 4.74 (1H, dd, J = 13.2 & 2.9 Hz), 5.14 (2H, s) and 7.81 (1H, s),

respectively. Similarly, in its 13


-CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.02, 52.99, 62.26, 68.29, 69.25

and 161.97, respectively. The peaks of all other protons and carbons of the molecule were

also present in the 1H and

13C NMR spectra of the compound. Based on the spectral data

analysis, the structure of the compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(4-

flourophenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74r).


96

2.7.50. 3-Hexyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-


Compound 74s was synthesized by click reaction of


methylcoumarin 67 and 4-(prope-2-yn-1-yloxy)-1,1'-

biphenyl 72s in t-BuOH/H2O/THF (3 mL, 1/1/1)






1707 cm-1




m), 4.48-4.58 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.29 (2H, s), and 7.83 (1H,

s),respectively. Similarly, in its 13

C NMR spectrum, the characteristic peaks for -

(CH2)5CH3, -CH2N, -CH, -OCH2, -CH2OPh and CO appeared at δ 14.03, 53.03, 61.65,

68.29, 69.27 and 161.93,r espectively. The peaks of all other protons and carbons of the




hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin

(74s).

2.7.51. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74t)

Compound 74t was synthesized by click

reaction of 7-(3-azido-2-hydroxypropyloxy)-

3-hexyl-4-methylcoumarin 67 and 4-(prope-2-

yn-1-yloxy)-1,1'-biphenyl 72t in t-




97





molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -


7.3 Hz), 4.02-4.09 (2H, m), 4.51-4.57 (2H, m), 4.70 (1H, dd, J = 13.7 & 2.8 Hz), 5.23


C NMR spectrum,




13C NMR


compound was established as3-hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-

1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74t).

2.7.52. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74u)

Compound 74u was synthesized by click

reaction of 7-(3-azido-2-hydroxypropyloxy)-

3-hexyl-4-methylcoumarin 67 and 4-(prope-

1-yn-1-yloxy)-1,1'-biphenyl 72u in t-




peak at m/z




molecule. The characteristic peak of -(CH2)5CH3, -CH2N, -CH and -OCHα, -OCHβ, -


7.3 Hz), 4.01-4.08 (2H, m), 4.52-4.59 (2H, m), 4.70 (1H, dd, J = 13.9 & 3.7 Hz), 5.36


C NMR spectrum,



98



13C NMR


compound was established as 3-hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-

1,2,3-triazol-1-yl)propyloxy)-4-methylcoumarin (74u).

Figure 83:1H NMR spectrum of compound 74t (400 MHz, CDCl3)


99

Figure 84:13

C NMR spectrum of compound 74t (100.6 MHz, CDCl3)

Figure 85:1H NMR spectrum of compound 74u (400 MHz, CDCl3)


100

Figure 86:13

C NMR spectrum of compound 74u (100.6 MHz, CDCl3)


101

2.8. BIOLOGICAL ACTIVITY

The synthesized coumarin derivatives 66, 67, 69a-d, 70a-d, 73a-u and 74a-u were

evaluated for the antifungal inhibition. The detailed results of antifungal activity

evaluation on these compounds are shown in Table 2.

Table 2: Antifungal inhibitory activity of (22, 23, 25a-d, 26a-d, 29a-u and 30 a-u)

Comp. A. fumigatus

MIC

A. niger

MIC

A. flavus

MIC

μg/ml

(MDA)

μg/disc

(DDA)

μg/ml

(MDA)

μg/disc

(DDA)

μg/ml

(MDA)

μg/disc

(DDA)

66 15.62 3.91 62.50 15.62 125.00 31.25

67 62.50 15.62 62.50 31.25 250.00 62.50

69a 500.00 125.00 500.00 250.00 - -

69b 62.50 31.25 125.00 31.25 - -

69c 62.50 15.62 62.50 31.25 125.00 31.25

69d 125.00 31.25 125.00 31.25 250.00 62.50

70a 500.00 125.00 - - - -

70b 125.00 31.25 - - - -

70c 250.00 62.50 - - 500.00 125.00

70d 31.25 7.81 31.25 15.62 125.00 31.25

73a 500.00 125.00 250.00 62.50 500.00 125.00

73b 500.00 250.00 500.00 125.00 - -

73c 250.00 62.50 125.00 62.50 250.00 62.50

73d 125.00 31.25 125.00 31.25 250.00 125.00

73e - - - - - -

73f 500.00 125.00 500.00 250.00 - -

73g 500.00 125.00 500.00 250.00 - -


102

73h 500.00 125.00 250.00 125.00 - -

73i 62.50 15.62 125.00 31.25 125.00 31.25

73j - - - - - -

73k - - - - - -

73l - - 250.00 62.50 - -

73m - - - - - -

73n - - - - - -

73o - - - - - -

73p 500.00 250.00 500.00 125.00 - -

73q 500.00 125.00 - - - -

73r 62.50 15.62 62.50 31.25 250.00 62.50

73s - - - - - -

73t - - - - - -

73u - - - - - -

74a - - - - - -

74b - - - - - -

74c 500.00 250.00 500.00 125.00 - -

74d 500.00 125.00 250.00 62.50 - -

74e - - - - - -

74f 125.00 31.25 62.50 31.25 - -

74g - - - - - -

74h - - - - - -

74i 125.00 62.50 125.00 31.25 - -

74j - - - - - -

74k - - - - - -

74l - - - - - -


103

74m - - - - - -

74n - - - - - -

74o - - - - - -

74p 500.00 125.00 - - 500.00 125.00

74q 500.00 250.00 500.00 250.00 - -

74r 250.00 125.00 500.00 250.00 500.00 250.00

74s - - - - - -

74t - - - - - -

74u - - - - - -

‘-’ These compounds did not show any activity even at the highest tested concentration.

These results clearly show that among all the tested azido-coumarin and 1,2,3-triazole

containing coumarins, 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin 66

inhibited A. fumigatus at lowest concentration i. e. 3.91 μg/disc in disc diffusion (DDA)

and 15.62 μg/ml in microbroth dilution assays (DDA). In case of A. niger it showed

activity at 15.62 μg/disc in DDA and 62.50 μg/ml in MDA. While in case of A. flavus it

inhibited at 31.25 μg/disc in DDA and 125.00 μg/ml in MDA, 7-(2-hydroxy-3-(4-

hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-3-hexyl-4-methylcoumarin (70d) inhibited

at low concentration 7.81 μg/disc in DDA and 31.25 μg/ml in MDA in case of A.

fumigatus. In case of A. niger it showed activity at 15.62 μg/disc in DDA and 31.25

μg/ml in MDA. While in case of A. flavus it inhibited at 31.25 μg/disc in DDA and

125.00 μg/ml in MDA. Compounds 67, 69b, 69c, 69d, 69b, 73d, 73i, 73r, 74f and 74i

exhibited moderate to good antifungal activity whereas remaining compounds i. e. 69a,

70a, 70c, 73a, 73b, 73c, 73e, 73f, 73g, 73h, 73l, 73p, 73q, 73c, 74d, 74p, 74q and 74r

did not show any appreciable activity. And the rest are inactive as evident from the data

presented in the (Table 1).


104

2.9. CONCLUSION

Herein, we have reported the synthesis of a series of fifty two azido- and 1,2,3-

triazole containing coumarin derivatives 66, 67, 69a-d, 70a-d, 74a-u and 74a-u

(having C2 and C6 alkyl chain) and various alkynes by using Click reaction, and

all these synthesized compounds are novel and synthesized for the first time. All

these are well characterized from their spectral data (1H,

13C NMR, IR and HRMS

spectrometry).

Out of two azido coumarinyl derivatives the compound having C2 alkyl chain at

C-3 position of coumarin, i. e. 66 exhibited the best antifungal activity than

similar derivative having C6 alkyl chain 67. So, in case of azido derivatives it has

been observed that, with the increase in aliphatic chain length at the C-3 position

of coumarin, the antifungal activity decreases considerably.

The same pattern of activity was seen in all 1,2,3-triazolylcoumarin derivatives,

but surprisingly, one of the C6 derivative 70d shows superior activity than their C2

derivative and all the other 1,2,3-triazolylcoumarin derivatives.

We have compared all the aryl ethers linked 1,2,3-triazolylcoumarins by varying

the position (o-, m- and p-) and substituent on aryl ethers. The structure activity

relationship suggests that antifungal activity of 1,2,3-triazolylcoumarin

derivatives was in the order : p- >m- >o-. Also the increasing order of

electronegative substituent also increases the antifungal activity, while the

electron donating substituents are found almost inactive.

It has been observed that more electronegative group at p-position of aryl ethers

are responsible for better activity trend in 1,2,3-triazolylcoumarins.


105

2.10. EXPERIMENTAL

Melting points were determined on Buchi M-560 instrument and are uncorrected. The IR

spectra were recorded on a Perkin-Elmer model 2000 FT-IR spectrometer by making KBr

disc for solid samples and thin film for oils. The 1H- and

13C NMR spectra were recorded

on a Jeol alpha-400 spectrometer at 400 and 100.6 MHz, respectively, using TMS as

internal standard. The chemical shift values are on scale and the coupling constants (J)

are in Hz. Signals from OH groups in 1H NMR spectra recorded in CDCl3 were verified

by removing them by D2O exchange method. The mass spectra analyses were done on

microTOF-Q instrument from Bruker Daltonics, Bremen and were run in ESI positive

mode. Reactions were conducted under an atmosphere of nitrogen when anhydrous

solvents were used. Analytical TLCs were performed on precoated Merck silica-gel

60F254 plates; the spots were detected under UV light. Silica gel (100-200 mesh) was

used for column chromatography. Chemicals were obtained from commercial suppliers

and were used without any further purification unless otherwise noted.

2.10.1. General procedure for the synthesis of 3-alkyl-7-(2,3-epoxypropyloxy)-4-

methylcoumarins (64 and 65)

This is two steps synthesis. The first step was synthesis of C-3 substituted coumarin, via.

Pechmann condensation of resorcinol (1.0 g, 9 mmol) and alkylated ethyl acetoacetate

(60a,1.63 mL, 15.43 mmol) or (60b, 3.22 mL, 15.43 mmol) in concentrated sulfuric acid

(5 mL, dropwise) at 0 oC. The mixture was stirred at room temperature for 3-4 h. On

completion of the reaction, 100 mL ice/water was added. The crude solid so obtained was

then filtered, washed with water, dried and crystallized from ethanol to give the

coumarins (62, 78 %) / (63, 80 %) as pale yellow coloured crystals. In second step, 3-

alkyl-7-hydroxy-4-methylcoumarin (62 and 63, 5.68mmol) was added into a 50 mL 0.6

M NaOH solution in methanol with constant stirring at 0 °C. To this solution

epichlorohydrin (8.52 mmol) was added dropwise and the reaction was stirred for 24 hr at

room temperature. The progress of the reaction was monitored on TLC. After completion

of the reaction, methanol was completely evaporated under reduced pressure and the


106

residue thus obtained was extracted with chloroform (4 x 50 mL) and washed with brine

(2 x 20 mL). Organic layer was separated and dried over anhydrous Na2SO4. The solvent

was removed under reduced pressure and the crude product, thus obtained was purified

by column chromatography on silica gel using EtOAc:petroleum ether (2:8) as an eluent

to obtain pure product 64/65.

2.10.1.1. 3-Ethyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (64)

It was obtained as white solid in 70 % yield; m. p 103-105 °C;IR (cm-1

, KBr):, 2859,

1720, 1607, 1389, 1281, 1151, 1069, and 841 cm-1

; 1H NMR (400 MHz, CDCl3): δ 1.14

(3H, t, J = 8.1 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.66 ( 2H, q, J = 7.3 Hz, -CH2CH3),

2.79 (1H, dd, J = 5.1 & 2.9 Hz, -CHα), 2.94 (1H, t, J = 5.1 Hz, -CHβ), 3.39 (1H, m, -CH),

3.96 (1H, dd, J = 11 & 5.9 Hz, -OCHα), 4.33 (1H, dd, J = 11 & 2.9 Hz, -OCHβ), 6.80

(1H, d, J = 2.2 Hz, C-8H), 6.89 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 7.51 (1H, d, J = 8.8

Hz, C-5H); 13

C NMR (100.6 MHZ, CDCl3): δ 13.04 (-CH2CH3), 14.48 (C-4 CH3), 20.74

(-CH2CH3), 44.49 (-CH2), 49.77 (-CH), 69.02 (-OCH2), 101.21 (C-8), 112.23 (C-6),

114.63 (C-10), 125.11 (C-3), 125.43 (C-5), 145.67 (C-9), 153.42 (C-4), 160.21 (C-7),

161.81 (CO); HR-ESI-TOF-MS m/z 261.1115 ([M+H]+), calcd for [C15H16O4+H]

+

261.1121.

2.10.1.2. 3-Hexyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (65)


, KBr):, 2851,

1718, 1610, 1389, 1277, 1121, 1060, and 844 cm-1

; 1H NMR (400 MHz, CDCl3): δ 0.89

(3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.28-1.41 (6H, m, -CH2CH2(CH2)3CH3), 1.48-1.55 (2H,

m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3), 2.62 ( 2H, t, J = 7.3 Hz, -

CH2(CH2)4CH3), 2.79 (1H, dd, J = 4.4 & 2.2 Hz, -CHα), 2.94 (1H, t, J = 5.1 Hz, -CHβ),

3.39 (1H, m, -CH), 3.96 (1H, dd, J = 11 & 5.9 Hz, -OCHα), 4.33 (1H, dd, J = 10.9 & 2.9

Hz, -OCHβ), 6.80 (1H, d, J = 2.2 Hz, C-8H), 6.89 (1H, dd, J = 9.5 and 2.9 Hz, C-6H),

7.51 (1H, d, J = 8.8 Hz, C-5H); 13

C NMR (100.6 MHZ, CDCl3): δ 13.04 (-(CH2)5CH3),

14.48 (C-4CH3), 20.74 (-CH2(CH2)3CH2CH3), 25.40 (-CH2CH2(CH2)3CH3), 27.40 (-


107

(CH2)2CH2(CH2)2CH3), 29.9 (-(CH2)3CH2CH2CH3), 44.51 (-CH2), 49.78 (-CH), 69.03 (-

OCH2), 101.21 (C-8), 112.24 (C-6), 114.67 (C-10), 124.03 (C-3), 125.44 (C-5), 145.84

(C-4), 153.44 (C-9), 160.19 (C-7), 161.95 (CO); HR-ESI-TOF-MS m/z 317.1743

([M+H]+), calcd for [C19H24O4+H]

+ 317.1747.

2.10.2. Synthesis of 3-alkyl-7-(3-azido-2-hydroxypropyloxy)-4-methylcoumarin (66

and 67)

3-Alkyl-7-(2,3-epoxypropyloxy)-4-methylcoumarin (43.10 mmol), sodium azide (215.51

mmol) and ammonium chloride (103.44 mmol) were added to a 50 mL methanol-water

(4:1 v/v) solution. The reaction was carried out at 70 °C and the conversion and synthesis

of the product was monitored by TLC. Upon completion of the reaction, the methanol

was evaporated, 50 mL of water was added to the residue and the product extracted with

CHCl3 (3 x 30 mL). The organic layers were combined and dried over Na2SO4. The

alcohol 66 and 67 was purified by column chromatography using EtOAc : petroleum

ether (1:9) as an eluent to obtain pure product 66 and 67.

2.10.2.1. 7-(3-Azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin (66)


, KBr):, 2858, 2113,

1714, 1617, 1392, 1288, 1156, 1078, and 746 cm-1

; 1H NMR (400 MHz, CDCl3): δ 1.14

(3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.66 (2H, q, J = 7.3 Hz, -CH2CH3),

3.52-3.61 (2H, m, -CH2N), 4.07-4.27 (3H, m, -CH & -OCH2), 6.80 ( 1H, d, J = 2.2 Hz,

C-8H), 6.86 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 7.50 (d, 1H, J = 8.8 Hz, C-5H); 13

C NMR

(100.6 MHZ, CDCl3): δ 13.03 (-CH2CH3), 14.49 (C-4 CH3), 20.74 (-CH2CH3), 53.27 (-

CH2N3), 68.96 (-OCH2), 69.36 (-CH), 101.29 (C-8), 112.06 (C-6), 114.74 (C-10), 125.16

(C-3H), 125.47 (C-5), 145.82 (C-9), 153.36 (C-4), 160.07 (C-7), 161.94 (CO); HR-ESI-

TOF-MS m/z 326.1099 ([M+Na]+), calcd for [C15H17N3O4+Na]

+ 326.1111.

2.10.2.2. 7-(3-Azido-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarin (67)


108


, KBr):, 2860, 2111,

1710, 1614, 1389, 1279, 1183, 1092, and 747 cm-1

; 1H NMR (400 MHz, CDCl3): δ 0.88

(3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.30-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.47-1.53 (2H,

m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3), 2.63 (2H, t, J = 7.3 Hz, -

CH2(CH2)4CH3), 3.52-3.60 (2H, m, -CH2N), 4.06-4.23 (3H, m, -CH & -OCH2), 6.79 (

1H, d, J = 2.2 Hz, C-8H), 6.86 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 7.51 (d, 1H, J = 8.8 Hz,

C-5H); 13

C NMR (100.6 MHZ, CDCl3): δ 14.03 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.57 (-

CH2(CH2)3CH2CH3), 27.47 (-CH2CH2(CH2)2CH3), 29.31 (-(CH2)2CH2(CH2)2CH3), 31.63

(-(CH2)3CH2CH2CH3), 53.26 (-CH2N3), 68.97 (-OCH2), 69.35 (-CH), 101.28 (C-8),

112.03 (C-6), 114.76 (C-10), 124.06 (C-3H), 125.47 (C-5), 145.98 (C-9), 153.36 (C-4),

160.03 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 360.1900 ([M+Na]+), calcd for

[C19H25N3O4+Na]+

360.1918.

2.10.3. General procedure for the synthesis of propargyl ethers of substituted

phenols 72a-u

To a stirred solution of substituted phenols (50 mmol) in acetone, equimolar amount of

propargyl bromide and K2CO3 were added. The reaction mixture was refluxed at 60 °C

for 12 hr.On completion of the reaction as indicated by the TLC, the solution was

evaporated at reduced pressure and then water (30 mL) was added. Subsequently, the

mixture was extracted with chloroform (3 x 30 mL), and organic phases were combined,

dried over anhydrous Na2SO4 and then evaporated under reduced pressure to produce

propargyl ethers 72a-u. The propargyl ethers of substituted phenols were used in the

following reactions without further purification.

2.10.4. General procedure for the synthesis of 7-(2-hydroxy-3-(4-substituted-1,2,3-

triazol-1-yl)propyloxy)-3-alkyl-4-methylcoumarins 69a-d, 70a-d, 73a-u and

74a-u

To a solution of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl/hexyl-4-methylcoumarin

(66/67, 3.60 mmol) and commercially available alkynes 68a-d (4.32 mmol) or propargyl

ethers of substituted phenols 72a-u (4.32 mmol) in t-BuOH/H2O/THF (3 mL, 1/1/1,

v/v/v), was added sodium ascorbate(1.29 mmol) and copper (II) sulfate pentahydrate


109

(0.54 mmol). Thereafter the reaction mixture was stirred at 60 °C and the reaction was

monitored by TLC. On completion of the reaction the solvent was evaporated under

reduced pressure and the crude product thus obtained was purified by silica gel column

chromatography using methanol/chloroform as eluting solution to afford the desired

products 69a-d, 70a-d, 73a-uand 74a-u.

2.10.4.1.1. 3-Ethyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-


It was obtained as white solid in 85 % yield; m. p 140-143 °C; IR (cm-1

, KBr): 3386,

2925, 2854, 1708, 1610, 1387, 1253, 1172, 1093 and 766 cm-1

; 1H NMR (400 MHz,

DMSO-d6): δ 1.04 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H,s, C-4 CH3), 2.57 (2H, q, J =

7.3 Hz, -CH2CH3), 4.08-4.16 (2H, m, -CH2N), 4.31-4.35 (1H, m, -CH), 4.48 (1H, dd, J =

10.3 & 7.3 Hz, -OCHα), 4.68 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.70 (1H, d, J = 5.8

Hz, OH), 6.97-7.00 (2H, m, C-6H, C-8H), 7.31 (1H, t, J = 7.4 Hz, ArH), 7.42-7.47 (2H,

m, ArH), 7.71 (1H, d, J = 9.5 Hz, C-5H), 7.85-7.86 (2H, m, ArH), 8.57 (1H, s, triazole

H); 13

C NMR (100.6 MHZ, DMSO-d6): δ 12.97 (-CH2CH3), 14.32 (C-4 CH3), 20.21 (-

CH2CH3), 52.71 (-CH2N), 67.69 (-CH), 70.09 (-OCH2), 101.06 (C-8), 112.31 (C-6),

113.87 (C-10), 122.45 (C-3), 123.81 (CH=C), 125.10 (2-ArC), 126.32 (C-5), 127.75,

128.88, 130.86 (4-ArC), 146.09 (CH=C), 156.39 (C-9), 153.04 (C-4), 160.43 (C-7),

160.75 (CO); HR-ESI-TOF-MS m/z 406.1751 ([M+H]+), calcd for [C23H23N3O4+H]

+

406.1761.

2.10.4.1.2. 3-Ethyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-

methylcoumarin(69b)


, KBr): 3461,

2920, 2859, 1704, 1617, 1303, 1211, 1159, 1089 and 865 cm-1

; 1H NMR (400 MHz,

DMSO-d6): δ 1.05 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.53-2.60 (4H,

m, -CH2CH3 and -CH2CH2COOH), 2.85 (2H, t, J = 7.3 Hz, -CH2CH2COOH), 4.01-4.08

(2H, m, -CH2N), 4.20-4.26 (1H, m, -CH), 4.39 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.55

(1H, dd, J = 13.9 & 3.6 Hz, -OCHβ), 5.61 (1H, brs, OH), 6.95-6.97 (2H, m, C-6H, C-8H),


110

7.70 (1H, d, J = 8.7 Hz, C-5H), 7.85 (1H, s, triazole H), 12.17 (1H, s, -CH2CH2COOH);

13C NMR (100.6 MHZ, DMSO-d6): δ 12.89 (-CH2CH3), 14.25 (C-4 CH3), 20.15 (-

CH2CH3), 20.60 (-CH2CH2COOH), 33.09 (-CH2CH2COOH), 52.28 (-CH2N), 67.65 (-

CH), 70.00 (-OCH2), 100.95 (C-8), 112.23 (C-6), 113.79 (C-10), 122.92 (C-3), 123.75

(CH=C), 126.24 (C-5), 145.36 (CH=C), 146.33 (C-9), 152.96 (C-4), 160.35 (C-7), 160.69

(CO), 173.58 (COOH); HR-ESI-TOF-MS m/z 402.1656 ([M+H]+), calcd for

[C20H23N3O6+H]+

402.1660.

2.10.4.1.3. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-ethyl-

4-methylcoumarin (69c)


, KBr): 3398,

2922, 2854, 1713, 1609, 1387, 1281, 1181, 1093 and 822 cm-1

; 1H NMR (400 MHz,

DMSO-d6): δ 1.05 (3H, t, J = 7.3 Hz, -CH2CH3), 2.04 (2H, pentate, -CH2CH2CH2Cl),

2.39 (3H, s, C-4 CH3), 2.56 (2H, q, J = 7.3 Hz, -CH2CH3), 2.75 (2H, t, J = 7.7 Hz, -

CH2CH2CH2Cl), 3.67 (2H, t, J = 6.9 Hz, -CH2CH2CH2Cl), 4.01-4.07 (2H, m, -CH2N),

4.21-4.26 (1H, m, -CH), 4.41 (1H, dd, J = 13.9 & 7.4 Hz, -OCHα), 4.56 (1H, dd, J = 13.9

& 3.6 Hz, -OCHβ), 5.62 (1H, d, J = 5.1 Hz, OH), 6.95-6.98 (2H, m, C-6H & C-8H), 7.70

(1H, d, J = 8.7 Hz, C-5H), 7.89 (1H, s, triazole H); 13

C NMR (100.6 MHZ, DMSO-d6): δ

12.96 (-CH2CH3), 14.32 (C-4 CH3), 20.20 (-CH2CH3), 22.28 (-CH2CH2CH2Cl), 31.79 (-

CH2CH2CH2Cl), 44.68 (-CH2CH2CH2Cl), 52.34 (-CH2N), 67.68 (-CH), 70.07 (-OCH2),

101.00 (C-8), 112.29 (C-6), 113.85 (C-10), 123.14 (C-3), 123.80 (CH=C), 126.31 (C-5),

145.17 (CH=C), 146.39 (C-9), 153.03 (C-4), 160.42 (C-7), 160.74 (CO); HR-ESI-TOF-

MS m/z 406.1521 ([M+H]+), calcd for [C20H24ClN3O4+H]

+ 406.1528.

2.10.4.1.4. 3-Ethyl-7-(2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-



, KBr): 3305,

2922, 2854, 1676, 1617, 1307, 1230, 1163, 1098 and 828 cm-1

; 1H NMR (400 MHz,

DMSO-d6): δ 0.96 (3H, t, J = 7.3 Hz, -CH2CH3), 2.31 (3H, s, C-4 CH3), 2.47 (2H, q, J =

7.3 Hz, -CH2CH3), 3.92-3.99 (2H, m, -CH2N), 4.13-4.20 (1H, m, -CH), 4.36 (1H, dd, J =


111

13.9 & 8.1 Hz, -OCHα), 4.43 (2H, d, J = 5.1 Hz, -CH2OH), 4.49 (1H, dd, J = 13.9 & 3.7

Hz, -OCHβ), 5.10 (1H, t, J = 5.5 Hz, -CH2OH), 5.54 (1H, d, J = 5.8 Hz, OH), 6.88-6.90

(2H, m, C-6H, C-8H), 7.63 (1H, d, J = 9.6 Hz, C-5H), 7.86 (1H, s, triazole H); 13

C NMR

(100.6 MHz, DMSO-d6): δ 12.99 (-CH2CH3), 14.36 (C-4 CH3), 20.24 (-CH2CH3), 52.33

(-CH2N), 55.08 (-CH=C-CH2), 67.75 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.33 (C-6),

113.89 (C-10), 123.73 (C-3), 123.84 (-CH=C), 126.36 (C-5), 146.45 (-CH=C), 147.75

(C-9), 153.05 (C-4), 160.45 (C-7), 160.79 (CO); HR-ESI-TOF-MS m/z 382.1365

([M+Na]+), calcd for [C18H21N3O5+Na]

+ 382.1373.

2.10.4.1.5. 3-Hexyl-7-(2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy)-4-



, KBr): 3386,

2925, 2854, 1708, 1610, 1387, 1253, 1172, 1093 and 766 cm-1

; 1H NMR (400 MHz,

DMSO-d6): δ 0.86 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.27-1.33 (6H, m, -

CH2CH2(CH2)3CH3), 1.39-1.43 (2H, m, -CH2CH2(CH2)3CH3), 2.38 (3H, s, C-4 CH3),

2.53 (2H, q, J = 7.3 Hz, -CH2(CH2)4CH3), 4.06-4.14 (2H, m, -CH2N), 4.31-4.35 (1H, m, -

CH), 4.50 (1H, dd, J = 13.9 & 8.4 Hz, -OCHα), 4.68 (1H, dd, J = 13.9 & 3.6 Hz, -OCHβ),

5.70 (1H, d, J = 5.1 Hz, OH), 6.96-6.99 (2H, m, C-6H & C-8H), 7.33 (1H, t, J = 7.4 Hz,

ArH), 7.45 (2H, t, J = 7.7 Hz, ArH), 7.70 (1H, d, J = 9.6 Hz, C-5H), 7.86 (2H, d, J = 7.3

Hz, ArH), 8.57 (1H, s, triazole H); 13

C NMR (100.6 MHZ, DMSO-d6): δ 13.96 (-

(CH2)5CH3), 14.63 (C-4 CH3), 22.70 (-CH2(CH2)3CH2CH3), 27.40 (-CH2CH2(CH2)3CH3),

29.4 (-(CH2)2CH2(CH2)2CH3), 31.90 (-(CH2)3CH2CH2CH3), 52.70 (-CH2N), 67.69 (-CH),

70.09 (-OCH2), 101.05 (C-8), 112.30 (C-6), 113.86 (C-10), 122.45 (C-3), 123.81

(CH=C), 125.10 (2-ArC), 126.32 (C-5), 127.75,128.87, 130.86 (4-ArC), 146.08 (CH=C),

156.39 (C-9), 153.04 (C-4), 160.42 (C-7), 160.75 (CO); HR-ESI-TOF-MS m/z 462.2381

([M+H]+), calcd for [C27H31N3O4+H]

+ 462.2387.

2.10.4.2. 3-Hexyl-7-(2-hydroxy-3-(4-propanoicacid)-1,2,3-triazol-4-yl)propyoxl)-4-

methylcoumarin(70b)


, KBr): 3461,

2920, 2859, 1704, 1617, 1303, 1211, 1159, 1084 and 865 cm-1

; 1H NMR (400 MHz,


112



2.53-2.67 (4H, m, -CH2(CH2)4CH3 and -CH2CH2COOH), 2.85 (2H, t, J = 7.3 Hz, -

CH2CH2COOH), 3.99-4.07 (2H, m, -CH2N), 4.20-4.23 (1H, m, -CH), 4.40 (1H, dd, J =

13.9 & 7.3 Hz, -OCHα), 4.55 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.61 (1H, d, J = 5.1

Hz, OH), 6.95-6.98 (2H, m, C-6H & C-8H), 7.69 (1H, d, J = 9.5 Hz, C-5H), 7.84 (1H, s,

triazole H), 12.17 (1H, d, -CH2CH2COOH); 13

C NMR (100.6 MHZ, DMSO-d6): δ 13.96

(-(CH2)5CH3, C-4 CH3), 14.63 (-CH2(CH2)3CH2CH3), 20.69 (-CH2CH2COOH), 22.07 (-

CH2CH2(CH2)CH3), 28.20 (-(CH2)2CH2(CH2)2CH3), 31.12 (-(CH2)3CH2CH2CH3), 33.17

(-CH2CH2COOH), 52.36 (-CH2N), 67.73 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.32

(C-6), 113.87 (C-10), 122.61 (C-3), 123.00 (CH=C), 126.34 (C-5), 145.45 (CH=C),

146.67 (C-9), 153.05 (C-4), 160.44 (C-7), 160.93 (CO), 173.66 (COOH); HR-ESI-TOF-

MS m/z 458.2284 ([M+H]+), calcd for [C24H31N3O6+H]

+ 458.2286.

2.10.4.3. 7-(3-(4-(3-Chloropropyl)-1,2,3-triazol-1-yl)-2-hydroxypropyloxy)-3-hexyl-4-



, KBr): 3398, 2922,

2854, 1713, 1609, 1387, 1252, 1181, 1093 and 779 cm-1

; 1H NMR (400 MHz, DMSO-

d6): δ 0.84 (3H, t, J = 6.6 Hz, -(CH2)5CH3), 1.23-1.34 (6H, m, -CH2CH2(CH2)3CH3),

1.37-1.44 (2H, m, -CH2CH2(CH2)3CH3), 2.02 (2H, pentate, -CH2CH2CH2Cl), 2.36 (3H, s,

C-4 CH3), 2.48-2.52 (2H, m, -CH2(CH2)4CH3), 2.73 (2H, t, J = 7.4 Hz, -CH2CH2CH2Cl),

3.65 (2H, t, J = 6.9 Hz, -CH2CH2CH2Cl), 3.96-4.05 (2H, m, -CH2N), 4.20-4.24 (1H, m, -


5.61 (1H, d, J = 5.8 Hz, OH), 6.92-6.95 (2H, m, C-6H, C-8H), 7.67 (1H, d, J = 8.8 Hz, C-

5H), 7.87 (1H, s, triazole H); 13

C NMR (100.6 MHZ, DMSO-d6): δ 13.96 (-(CH2)5CH3),

14.63 (C-4 CH3), 22.08 (-CH2CH2(CH2)3CH3), 22.29 (-(CH2)4CH2CH3), 26.82 (-

CH2CH2CH2Cl), 28.20 (-CH2CH2(CH2)3CH3), 28.67 (-(CH2)2CH2(CH2)2CH3), 31.13 (-

(CH2)3CH2CH2CH3), 31.82 (-CH2CH2CH2Cl), 44.69 (-CH2CH2CH2Cl), 52.36 (-CH2N),

67.71 (-CH), 70.08 (-OCH2), 101.01 (C-8), 112.29 (C-6), 113.86 (C-10), 122.60 (C-3),

123.16 (CH=C), 126.33 (C-5), 145.20 (CH=C), 146.65 (C-9), 153.04 (C-4), 160.42 (C-7),


113

160.92 (CO); HR-ESI-TOF-MS m/z 462.2157 ([M+H]+), calcd for [C24H32ClN3O4+H]

+

462.2154.

2.10.4.4. 3-Hexyl-7-(2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-



, KBr): 3305,

2922, 2854, 1676, 1617, 1307, 1230, 1163, 1013 and 828 cm-1

; 1H NMR (400 MHz,



2.50-2.55 (2H, m, -CH2(CH2)4CH3), 4.00-4.05 (2H, m, -CH2N), 4.23-4.26 (1H, m, -CH),

4.44 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.52 (2H, d, J = 5.8 Hz, -CH2OH), 4.58 (1H,

dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.18 (1H, t, J = 5.9 Hz, -CH2OH) 5.62 (1H, d, J = 5.9 Hz,

OH), 6.96-6.98 (2H, m, C-6H, C-8H), 7.70 (1H, d, J = 9.5 Hz, C-5H), 7.95 (1H, s,

triazole H); 13

C NMR (100.6 MHz, DMSO-d6): δ 12.99 (-(CH2)5CH3), 14.36 (C-4 CH3),

22.50 (-CH2(CH2)3CH2CH3), 27.40 (-CH2CH2(CH2)3CH3), 31.90 (-(CH2)3CH2CH2CH3),

52.33 (-CH2N), 55.07 (-CH=C-CH2), 67.75 (-CH), 70.09 (-OCH2), 101.04 (C-8), 112.33

(C-6), 113.88 (C-10), 123.72 (C-3), 123.84 (-CH=C), 126.36 (C-5), 145.75 (-CH=C),

147.29 (C-9), 153.05 (C-4), 160.45 (C-7), 160.79 (CO); HR-ESI-TOF-MS m/z 416.2176


+ 416.2180.

2.10.4.4.1. 3-Ethyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)propyloxy)-4-



, KBr): 3386,

2925, 2854, 1717, 1610, 1387, 1253, 1172, 1093, and 766 cm-1

; 1H NMR (400 MHz,

CDCl3): δ 1.10 (3H, t, J = 7.1 Hz, -CH2CH3), 2.34 (3H, s, C-4 CH3), 2.62 (2H, q, J = 7.3

Hz, -CH2CH3), 3.45 (1H, brs, OH), 4.01-4.05 (2H, m, -CH2N), 4.47-4.56 (2H, m, -CH &

-OCHα), 4.69 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh), 6.72-6.73 (1H,

m, C-8H), 6.80 (1H, dd, J = 8.7 & 2.3 Hz, C-6H), 6.90 (3H, m, ArH), 7.24 (2H, t, J = 7.3

Hz, ArH), 7.44 (1H, d, J = 8.8 Hz, C-5H), 7.78 (1H, s, triazole H); 13

C NMR (100.6

MHz, CDCl3): δ 13.03 (-CH2CH3), 14.48 (C-4 CH3), 20.72 (-CH2CH3), 52.99 (-CH2N),


114

61.59 (-OCH2Ph), 68.29 (-CH), 69.25 (-OCH2), 101.28 (C-8), 112.15 (C-6), 114.60 (C-

10), 114.71 (2-ArC), 121.21 (C-3), 124.59 (CH=C), 125.05 (ArC), 125.48 (C-5), 129.46

(2-ArC), 143.88 (CH=C), 145.91 (C-9), 153.26 (C-4), 158.02 (C-7), 159.93 (ArC),


+

436.1867.

2.10.4.5. 3-Ethyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3392,

2926, 2367, 1718, 1617, 1458, 1251, 1170, 1087, and 759 cm-1

; 1H NMR (400 MHz,



-OCHα), 4.74 (1H, dd, J = 13.2 & 2.2 Hz, -OCHβ), 5.25 (2H, s, -CH2OPh), 6.76 (1H, d, J

= 2.9 Hz, C-8H), 6.83 (1H, dd, J = 5.8 & 2.9 Hz, C-6H), 6.87-6.91 (1H, m, ArH), 7.05-

7.21 (2H, m, ArH), 7.31-7.33 (1H, m, ArH), 7.48 (1H, d, J = 9.5 Hz, C-5H), 7.86 (1H, s,

triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.03 (-CH2CH3), 14.48 (C-4CH3), 20.73

(-CH2CH3), 53.02 (-CH2N), 62.97 (-OCH2Ph), 68.30 (-CH), 69.24 (-OCH2), 101.24 (C-

8), 112.16 (C-6), 114.06 (C-3), 114.71 (C-10), 122.02 (2-ArC), 122.91 (CH=C), 124.69

(ArC), 125.06 (C-5), 127.74, 130.24 (2-ArC), 143.62 (CH=C), 145.91 (C-9), 153.27 (C-

4), 153.54 (C-7), 159.92 (ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 470.1477 ([M+H]+),

calcd for [C24H24ClN3O5+H]+

470.1477.




, KBr): 3392,

2954, 2853, 1718, 1611, 1493, 1387, 1285, 1169, 1091, and 825 cm-1

; 1H NMR (400

MHz, CDCl3): δ 1.08 (3H, t, J = 7.3 Hz, -CH2CH3), 2.35 (3H, s, C-4 CH3), 2.62 (2H, q, J

= 7.4 Hz, -CH2CH3), 3.76 (1H, brs, OH), 4.01-4.06 (2H, m, -CH2N), 4.50-4.60 (2H, m, -

CH& -OCHα), 4.71 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.13 (2H, s, -CH2OPh), 6.74-

6.93 (5H, m, C-6H & C-8H, ArH), 7.15 (1H, t, J = 8.1 Hz, ArH), 7.45 (1H, d, J = 8.8 Hz,

C-5H), 7.79 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.03 (-CH2CH3),


115

14.50 (C-4 CH3), 20.74 (-CH2CH3), 53.00 (-CH2N), 61.87 (-OCH2Ph), 68.32 (-CH),

69.26 (-OCH2), 101.29 (C-8), 112.13 (C-6), 112.96 (C-3), 114.77 (C-10), 115.22 (2ArC),

121.41 (CH=C), 124.69 (ArC), 125.12 (C-5), 125.51, 130.25 (2-ArC), 143.34 (CH=C),

145.89 (C-9), 153.28 (C-4), 158.74 (C-7), 159.90 (ArC), 161.94 (CO); HR-ESI-TOF-MS

m/z 470.1480 ([M+H]+), calcd for [C24H24ClN3O5+H]

+ 470.1477.




, KBr): 3392,

2927, 2859, 1718, 1607, 1389, 1281, 1151, 1069, and 841 cm-1

; 1H NMR (400 MHz,




= 2.9 Hz, C-8H), 6.81 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 6.85-6.88 (2H, m, ArH), 7.17-

7.21 (2H, m, ArH), 7.46 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13

C NMR

(100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.49 (C-4 CH3), 20.73 (-CH2CH3), 53.00 (-

CH2N), 61.89 (-OCH2Ph), 68.28 (-CH), 69.27 (-OCH2), 101.23 (C-8), 112.16 (C-6),

114.71 (C-10), 115.94 (2-ArC), 124.70 (C-3), 125.06 (CH=C), 125.49 (ArC), 126.07 (C-

5), 129.28 (2-ArC), 144.45 (CH=C), 145.95 (C-9), 153.23 (C-4), 156.59 (C-7), 159.89

(ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 470.1474 ([M+H]+), calcd for

[C24H24ClN3O5+H]+

470.1477.

2.10.4.8. 3-Ethyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3246,

2931, 2859, 1710, 1618, 1479, 1384, 1297, 1156, 1069, and 759 cm-1

; 1H NMR (400

MHz, CDCl3): δ δ 1.14 (3H, t, J = 7.3 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.65 (2H, q,

J = 8.1 Hz, -CH2CH3), 3.72 (1H, brs, OH), 4.03-4.09 (2H, m, -CH2N), 4.51-4.61 (2H, m,

-CH & -OCHα), 4.73 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.77

(1H, d, J = 2.9 Hz, C-8H), 6.81-6.86 (2H, m, C-6H & ArH), 7.03 (1H, dd, J = 8.1 & 1.8

Hz, ArH), 7.21-7.27 (1H, m, ArH), 7.47-7.51(2H, m, ArH, C-5H), 7.86 (1H, s, triazole


116

H); 13

C NMR (100.6 MHz, CDCl3): δ 13.08 (-CH2CH3), 14.55 (C-4CH3), 20.79 (-

CH2CH3), 52.94 (-CH2N), 63.25 (-OCH2Ph), 68.48 (-CH), 69.13 (-OCH2), 101.39 (C-8),

112.26 (C-6), 113.92 (C-3), 114.91 (C-10), 122.57 (2-ArC), 124.55 (CH=C), 125.30

(ArC), 125.57 (C-5), 128.55, 133.36 (2-ArC), 143.85 (CH=C), 145.76 (C-9), 153.38 (C-

4), 154.43 (C-7), 159.85 (ArC), 161.89 (CO); HR-ESI-TOF-MS m/z 514.0982 ([M+H]+),

calcd for [C24H24BrN3O5+H]+

514.0972.

2.10.4.9. 3-Ethyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3402,

2922, 2859, 1717, 1610, 1490, 1387, 1251, 1171, 1091 and 823 cm-1

; 1H NMR (400


= 7.3 Hz, -CH2CH3), 3.88 (1H, d, J = 4.4 HzOH), 4.03-4.10 (2H, m, -CH2N), 4.51-4.60

(2H, m, -CH & -OCHα), 4.74 (1H, dd, J = 13.9 & 2.9 Hz, -OCHβ), 5.14 (2H, s, -

CH2OPh), 6.75 (1H, d, J = 2.9 Hz, C-8H), 6.80-6.84 (3H, m, C-6H, ArH), 7.32-7.35 (2H,

m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13

C NMR (100.6 MHz,

CDCl3): δ 13.03 (-CH2CH3), 14.51 (C-4 CH3), 20.74 (-CH2CH3), 53.00 (-CH2N), 61.82 (-

OCH2Ph), 68.29 (-CH), 69.26 (-OCH2), 101.24 (C-8), 112.14 (C-6), 113.41 (C-3), 114.73

(C-10), 116.45 (2-ArC), 124.70 (CH=C), 125.08 (ArC), 125.50 (C-5), 132.22 (2-ArC),

143.42 (CH=C), 145.93 (C-9), 153.24 (C-4), 157.10 (C-7), 159.88 (ArC), 161.94 (CO);

HR-ESI-TOF-MS m/z 514.0965 ([M+H]+), calcd for [C24H24BrN3O5+H]

+ 514.0972.

2.10.4.10. 3-Ethyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3419,

2924, 2856, 1689, 1612, 1523, 1466, 1347, 1255, 1163, 1090 and 739 cm-1

; 1H NMR

(400 MHz, DMSO-d6): δ 1.14 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s, C-4 CH3), 2.57

(2H, q, J = 7.2 Hz, -CH2CH3), 4.01-4.10 (2H, m, -CH2N), 4.22-4.28 (1H, m, -CH), 4.48

(1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.62 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.36 (2H,

s, -CH2OPh), 5.64 (1H, d, J = 5.1 Hz, OH), 6.94-6.97 (2H, m, C-6H & C-8H), 7.11-7.15

(1H, m, ArH), 7.59-7.72 (3H, m, ArH), 7.85 (1H, d, J = 8.4 Hz, C-5H), 8.22 (1H, s,


117

triazole H); 13

C NMR (100.6 MHz, DMSO-d6): δ 12.89 (-CH2CH3), 14.25 (C-4 CH3),

20.14 (-CH2CH3), 52.49 (-CH2N), 62.48 (-OCH2Ph), 67.53 (-CH), 69.98 (-OCH2), 100.93

(C-8), 112.24 (C-6), 113.80 (C-10), 115.50 (2-ArC), 120.81 (CH=C), 123.75 (C-3),

124.85 (ArC), 125.84 (C-5), 126.25, 134.21 (2-ArC), 139.66 (CH=C), 146.34 (C-9),

150.54 (C-4), 152.96 (C-7), 160.32 (ArC), 160.69 (CO); HR-ESI-TOF-MS m/z 481.1711


+ 481.1718.




, KBr): 3210,

2929, 2869, 1716, 1618, 1527, 1350, 1251, 1163, 1062 and 829 cm-1

; 1H NMR (400



CH& -OCHα), 4.75 (1H, dd, J = 13.8 & 3.2 Hz, -OCHβ), 5.28 (2H, s, -CH2OPh), 6.76

(1H, d, J = 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.7 & 2.8 Hz, C-6H), 7.30-7.51 (3H, m,

ArH), 7.81-7.86 (3H, m, ArH, C-5H & triazole H); 13

C NMR (100.6 MHz, CDCl3): δ

12.95 (-CH2CH3), 14.31 (C-4 CH3), 20.21 (-CH2CH3), 52.55 (-CH2N), 61.76 (-OCH2Ph),

67.61 (-CH), 70.06 (-OCH2), 101.03 (C-8), 109.06 (C-6), 112.29 (C-10), 113.88, 115.76

(2-ArC), 122.17 (CH=C), 123.84 (C-3), 125.91 (ArC), 126.30 (C-5), 130.66 (ArC),

141.68 (ArC), 146.39 (CH=C), 148.70 (C-9), 153.02 (C-4), 158.55 (C-7), 160.38 (ArC),


+

481.1718.




, KBr): 3367,

2929, 2856, 1699, 1610, 1510, 1332, 1256, 1173, 1086 and 834 cm-1

; 1H NMR (400

MHz, DMSO-d6): δ 1.04 (3H, t, J = 7.3 Hz, -CH2CH3), 2.39 (3H, s,C-4 CH3), 2.55 (2H,

q, J = 7.3 Hz, -CH2CH3), 4.00-4.10 (2H, m, -CH2N), 4.22-4.29 (1H, m, -CH), 4.48 (1H,

dd, J = 13.9 & 7.3 Hz, -OCHα), 4.63 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.33 (2H, s, -

CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.95-6.97 (2H, m, C-6H, C-8H), 7.26-7.28 (2H,


118

m, ArH), 7.70 (1H, d, J = 8.8 Hz, C-5H), 8.18-8.23 (2H, m, ArH), 8.27 (1H, s, triazole

H); 13

C NMR (100 MHz, DMSO-d6): δ 12.88 (-CH2CH3), 14.24 (C-4 CH3), 20.15 (-


112.20 (C-6), 113.80 (C-10), 115.21 (2ArC), 123.77 (C-3) (CH=C), 125.75, 125.99

(3ArC), 126.23 (C-5), 141.35 (CH=C), 146.32 (C-9), 152.95 (C-4), 160.30 (C-7), 160.68

(ArC), 163.23 (CO); HR-ESI-TOF-MS m/z 481.1703 ([M+H]+), calcd for

[C24H24N4O7+H]+

481.1718.

2.10.4.13. 3-Ethyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73j)


, KBr): 3385,

2922, 2852, 1716, 1611, 1387, 1250, 1121, 1025 and 748 cm-1

; 1H NMR (400 MHz,

CDCl3): δ 1.15 (3H, t, J = 8.1 Hz, -CH2CH3), 2.28 (Ph-CH3), 2.35 (3H, s, C-4 CH3), 2.63

(2H, q, J = 8.1 Hz, -CH2CH3), 3.85 (1H, d, J = 5.1 Hz, OH), 4.03-4.6 (2H, m, -CH2N),

4.47-4.57 (2H, m, -CH & -OCHα), 4.70 (1H, dd, J = 13.9 & 3.8 Hz, -OCHβ), 5.14 (2H, s,

-CH2OPh), 6.72-6.85 (5H, m, C-6H, C-8H & 3-ArH), 7.13 (1H, m, ArH), 7.46 (1H, d, J

= 8.7 Hz, C-5H), 7.77 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.02 (-

CH2CH3), 14.48 (Ph-CH3), 16.12 (C-4 CH3), 20.73 (-CH2CH3), 52.94 (-CH2N), 61.99 (-

OCH2Ph), 68.32 (-CH), 69.24 (-OCH2), 101.29 (C-8), 111.35 (C-6), 112.11 (ArC),

114.74 (C-10), 120.93 (ArC, CH=C), 124.30 (ArC), 125.10 (C-3H), 125.49 (ArC),

126.91 (C-5), 130.72 (ArC), 144.43 (CH=C), 145.87 (C-9), 153.29 (C-4), 156.20 (C-7),

159.94 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z 450.2010 ([M+H]+), calcd for

[C25H27N3O5+H]+

450.2023.

2.10.4.14. 3-Ethyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73k)


, KBr): 3511,

2924, 2852, 1718, 1610, 1458, 1259, 1173, 1085 and 777 cm-1

; 1H NMR (400 MHz,

CDCl3): δ 1.13 (3H, t, J = 7.4 Hz, -CH2CH3), 2.17 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.64

(2H, q, J = 8.1 Hz, -CH2CH3), 3.57 (d, 1H, J = 5.1 Hz, OH), 4.00-4.08 (2H, m, -CH2N),

4.48-4.60 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.18 (2H, s,


119

-CH2OPh), 6.76-6.92 (4H, m, C-6H, C-8H & ArH), 7.09-7.14 (2H, m, ArH), 7.47 (1H, d,

J = 8.7 Hz, C-5H), 7.75 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.02 (-

CH2CH3), 14.48 (C-4 CH3), 20.72 (-CH2CH3), 21.42 (Ph-CH3), 53.00 (-CH2N), 61.58 (-

OCH2Ph), 68.31 (-CH), 69.27 (-OCH2), 101.28 (C-8), 111.43 (C-6), 112.13 (C-3, ArC),

114.71 (C-10), 115.46 (ArC), 122.05 (CH=C), 124.53, 125.06 (2ArC), 129.17 (C-5),

139.52 (ArC), 143.99 (CH=C), 145.88 (C-9), 153.28 (C-4), 158.05 (C-7), 159.95 (ArC),


+

450.2023.

2.10.4.15. 3-Ethyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (73l)


, KBr): 3386,

2920, 2852, 1721, 1610, 1510, 1383, 1247, 1176, 1089 and 831 cm-1

; 1H NMR (400

MHz, CDCl3): δ 1.12 (3H, t, J = 7.3 Hz, -CH2CH3), 2.26 (Ph-CH3), 2.36 (3H, s, C-4

CH3), 2.64 (2H, q, J = 7.3 Hz, -CH2CH3), 3.78 (1H, d, J = 5.1 Hz, OH), 4.01-4.08 (2H,

m, -CH2N), 4.51-4.57 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ),

5.13 (2H, s, -CH2OPh), 6.75-6.85 (4H, m, C-6H, C-8H & ArH), 7.03-7.06 (2H, m, Ar′H),

7.46 (1H, d, J = 8.7 Hz, C-5H), 7.78 (1H, s, triazole H); 13

C NMR (100.6 MHZ, CDCl3):

δ 13.08 (-CH2CH3), 14.55 (C-4 CH3), 20.45 (-CH2CH3), 20.79 (Ph-CH3), 52.91 (-CH2N),

61.89 (-OCH2Ph), 68.51 (-CH), 69.17 (-OCH2), 101.46 (C-8), 111.97 (C-6), 114.54 (C-3,

ArC), 114.91 (C-10), 124.44 (ArC), 125.31 (CH=C), 125.57, 129.95 (3ArC), 130.56 (C-

5), 144.30 (CH=C), 145.76 (C-9), 153.38 (C-4), 155.96 (C-7), 159.86 (ArC), 161.91

(CO); HR-ESI-TOF-MS m/z 450.2023 ([M+H]+), calcd for [C25H27N3O5+H]

+ 450.2026.

2.10.4.16. 3-Ethyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (73m)


, KBr): 3401,

2963, 2859, 1674, 1605, 1508, 1387, 1254, 1122, 1030 and 735 cm-1

; 1H NMR (400



120

= 8.1 Hz, -CH2CH3), 3.80 (2H, m, Ph-OCH3 & OH), 4.01-4.05 (2H, m, -CH2N), 4.45-

4.54 (2H, m, -CH & -OCHα), 4.68 (1H, dd, J = 11.9 & 2.9 Hz, -OCHβ), 5.23 (2H, s, -

CH2OPh), 6.74 (1H, d, J = 2.9 Hz, C-8H), 6.79-6.94 (4H, m, C-6H & ArH), 6.98-7.00

(1H, m, ArH), 7.45 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13

C NMR (100.6

MHz, CDCl3): δ 13.03 (-CH2CH3), 14.49 (C-4 CH3), 20.74 (-CH2CH3), 52.94 (-CH2N),

55.72 (Ph-OCH3), 62.82 (-OCH2Ph), 68.36 (-CH), 69.22 (-OCH2), 101.32 (C-8), 111.77

(C-6), 112.07 (C-3), 114.27 (ArC), 114.75 (C-10), 120.78 (ArC), 121.88 (CH=C),

124.78, 125.12 (2ArC), 125.48 (C-5), 144.02 (ArC), 145.81 (CH=C), 147.42 (C-9),



+ 466.1973.

2.10.4.17. 3-Ethyl-7-(2-hydroxy-3-(4-(3-methoxyphenoxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (73n)


, KBr): 3228, 2938,

2859, 1708, 1617, 1458, 1295, 1155, 1057 and 841 cm-1

; 1H NMR (400 MHz, CDCl3): δ

1.13 (3H, t, J = 7.32 Hz, -CH2CH3), 2.37 (3H, s,C-4 CH3), 2.65 (2H, q, J = 7.32 Hz, -

CH2CH3), 3.71 ( 1H, brs, OH), 3.77 (1H, s, Ph-OCH3), 4.03-4.10 (m, 2H, -NCH2), 4.50-

4.59 (m, 2H, -CH, -OCHα), 4.72 (dd, 1H, J = 12.44 & 2.20 Hz, -OCHβ), 5.16 (s, 2H, -

CH2OPh), 6.51-6.57 (3H, m, C-6H, C-8H & ArH), 6.77-6.85 (2H, m, ArH), 7.14-7.19

(m, 1H, ArH), 7.48 (d, 1H, J = 8.80 Hz, C-5H), 7.80 (s, 1H, triazole H); 13

C NMR (100.6

MHz, CDCl3): δ 13.04 (-CH2CH3), 14.49 (C-4 CH3), 20.75 (-CH2CH3), 52.98 (-NCH2),

55.21 (Ph-OCH3), 61.76 (-OCH2Ph), 68.36 (-CH), 69.25 (-OCH2), 101.19 (C-8), 106.65

(C-6), 106.84 (C-3, ArC), 112.11 (C-10), 114.77 (ArC), 124.58 (CH=C), 125.13, 125.51

(2-ArC), 129.92 (C-5), 143.84 (ArC), 145.87 (CH=C), 153.31 (C-9), 159.29 (C-4),

159.92 (C-7), 160.74 (ArC), 161.94 (CO); HR-ESI-TOF-MS m/z 466.1975 ([M+H]+),

calcd for [C25H27N3O6+H]+

466.1973.

2.10.4.18. 3-Ethyl-7-(2-hydroxy-3-(4-(2-iodophenoxymethyl)-1,2,3-triazol-1-



121


, KBr): 3273,

2932, 2873, 1711, 1617, 1439, 1297, 1155, 1061 and 760; 1H NMR (400 MHz, CDCl3): δ

1.13 (3H, t, J = 7.3 Hz, -CH2CH3), 2.37 (3H, s, C-4 CH3), 2.64 (2H, q, J = 7.3 Hz, -

CH2CH3), 3.70 (1H, d, J = 5.2 Hz, OH), 4.03-4.08 (2H, m, -CH2N), 4.52-4.63 (1H, m, -

CH & -OCHα), 4.74 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.25 (2H, s, -CH2OPh), 6.69-

6.96 (4H, m, C-6H, C-8 & ArH), 7.25-7.30 (1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz, C-

5H), 7.72-7.74 (1H, m, ArH), 7.89 (1H, s, triazole H); 13


13.05 (-CH2CH3), 14.52 (C-4 CH3), 20.77 (-CH2CH3), 53.00 (-CH2N), 63.39 (-OCH2Ph),

68.39 (-CH), 69.19 (-OCH2), 101.36 (C-8), 112.13 (C-6), 112.27 (C-10), 114.48 (2ArC),

123.18 (C-3), 124.64 (CH=C), 125.54 (ArC), 129.55 (C-5), 139.38 (2ArC, CH=C),

145.83 (C-9), 153.33 (C-4), 156.59 (C-7), 159.92 (ArC), 161.92 (CO); HR-ESI-TOF-MS

m/z 562.0839 ([M+H]+), calcd for [C24H24IN3O5+H]

+ 562.0833.

2.10.4.19. 3-Ethyl-7-(2-hydroxy-3-(4-(4-iodophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3384,

2922, 2852, 1715, 1611, 1487, 1386, 1249, 1175, 1096 and 824 cm-1

; 1H NMR (400



CH & -OCHα), 4.71 (1H, dd, J = 13.2 & 3.7 Hz, -OCHβ), 5.11 (2H, s, -CH2OPh), 6.68-

6.82 (4H, m, C-6H, C-8H & ArH), 7.44-7.51 (3H, m, ArH, C-5H), 7.78 (1H, s, triazole

H); 13

C NMR (100.6 MHz, CDCl3): δ 13.05 (-CH2CH3), 14.55 (C-4 CH3), 20.76 (-


112.13 (C-6), 114.78 (C-10), 117.05 (2ArC, C-3), 124.69 (CH=C), 125.14 (ArC), 125.52

(C-5), 138.20 (2ArC, CH=C), 145.91 (C-9), 153.27 (C-4), 157.89 (C-7), 159.87 (ArC),

161.94 (CO);HR-ESI-TOF-MS m/z 562.0839 ([M+H]+), calcd for [C24H24IN3O5+H]

+

562.0833.

2.10.4.20. 3-Ethyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-



122


, KBr): 3392,

2935, 2875, 1706, 1616, 1490, 1298, 1160, 1070 and 840 cm-1

; 1H NMR (400 MHz,


Hz, -CH2CH3), 3.64 (1H, d, J = 5.1 Hz, OH), 4.00-4.07 (2H, m, -CH2N), 4.48-4.58 (2H,

m, -CH & -OCHα), 4.71 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.14 (2H, s, -CH2OPh),

6.62-6.82 (5H, m, C-6H, C-8H & ArH), 7.16-7.21 (1H, m, ArH), 7.46 (1H, d, J = 8.8 Hz,

C-5H), 7.79 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3),

14.48 (C-4 CH3), 20.73 (-CH2CH3), 53.01 (-CH2N), 61.89 (-OCH2Ph), 68.31 (-CH),

69.27 (-OCH2), 101.27 (C-8), 102.41 (C-6), 102.66 (C-3), 107.96 (C-10), 108.17, 110.26

(2ArC), 112.16 (CH=C), 114.74 (ArC), 124.71 (C-5), 125.50, 130.21 (2ArC), 145.95

(CH=C), 153.26 (C-9), 159.30 (C-4), 159.92 (C-7), 161.97 (ArC), 164.65 (CO); HR-ESI-

TOF-MS m/z 454.1773 ([M+H]+), calcd for [C24H24FN3O5+H]

+ 454.1773.

2.10.4.21. 3-Ethyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3384,

2963, 2873, 1705, 1616, 1510, 1298, 1159, 1095 and 822 cm-1

; 1H NMR (400 MHz,




6.76-6.97 (6H, m, C-6H, C-8H & ArH), 7.48 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s,

triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.48 (C-4 CH3), 20.74

(-CH2CH3), 52.98 (-CH2N), 62.31 (-OCH2Ph), 68.33 (-CH), 69.28 (-OCH2), 101.29 (C-

8), 112.15 (C-6), 114.77 (C-3), 115.70 (C-10), 115.74, 115.82 (2ArC), 115.93 (CH=C),

125.13 (ArC), 125.50 (C-5), 143.72, 145.91 (2ArC), 153.28 (CH=C), 154.13 (C-9),


([M+H]+), calcd for [C24H24FN3O5+H]

+ 454.1773.

2.10.4.22. 3-Ethyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-



123


, KBr): 3421,

2925, 2856, 1707, 1609, 1387, 1251, 1177, 1085 and 761 cm-1

; 1H NMR (400 MHz,




6.75 (1H, d, J = 2.3 Hz, C-8H), 6.80 (1H, dd, J = 2.8 & 8.7 Hz, C-6H), 6.99-7.02 (2H, m,

ArH), 7.26-7.52 (8H, m, C-5H, ArH), 7.80 (1H, s, triazole H); 13

C NMR (100.6 MHZ,

CDCl3): δ 13.02 (-CH2CH3), 14.45 (C-4 CH3), 20.72 (-CH2CH3), 53.03 (-CH2N), 61.75

(-OCH2Ph), 68.31 (-CH), 69.28 (-OCH2), 101.28 (C-8), 112.11 (C-6), 114.71 (C-10),

114.93 (2ArC), 124.66 (C-3), 125.47 (CH=C), 126.57 (C-5), 126.70 (3ArC), 128.05

(3ArC), 128.67 (2-ArC), 140.39 (ArC), 143.79 (CH=C), 145.89 (C-9), 153.26 (C-4),

157.58 (C-7), 159.91 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z 512.2171 ([M+H]+),

calcd for [C30H29N3O5+H]+ 512.2180.

2.10.4.23. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (73t)


, KBr): 3161,

2925, 2856, 1718, 1621, 1466, 1294, 1182, 1084 and 845 cm-1

; 1H NMR (400 MHz,




6.74 (1H, d, J = 2.2 Hz, C-8H), 6.79 (1H, dd, J = 2.2 & 8.8 Hz, C-8H), 7.10-7.22 (2H,

m, ArH), 7.29-7.73 (6H, m, C-5H, ArH), 7.81 (1H, s, triazole H); 13

C NMR (100.6 MHz,

CDCl3): δ 13.02 (-CH2CH3), 14.43 (C-4 CH3), 20.72 (-CH2CH3), 53.03 (-CH2N), 61.66 (-

OCH2Ph), 68.31 (-CH), 69.27 (-OCH2), 101.24 (C-8), 107.02 (ArC), 112.08 (C-6),

114.67 (C-10), 118.59 (ArC), 123.82 (C-3), 124.70 (ArC), 125.44 (CH=C), 127.52

(ArC), 129.46 (ArC), 143.71 (ArC), 145.88 (CH=C), 153.23 (C-4), 155.94 (C-9), 159.89

(C-7), 161.93 (CO); HR-ESI-TOF-MS m/z 486.2021 ([M+H]+), calcd for

[C28H27N3O5+H]+

486.2023.


124

2.10.4.24. 3-Ethyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (73u)


, KBr): 3374,

2932, 2872, 1698, 1608, 1389, 1268, 1151, 1097 and 771 cm-1

; 1H NMR (400 MHz,




= 2.9 Hz, C-8H), 6.78 (1H, dd, J = 2.2 & 8.8 Hz, C-6H), 6.89 (1H, d, J = 7.3 Hz, ArH),

7.28-7.46 (5H, m, ArH), 7.75 (1H, d, J = 8.1 Hz, C-5H), 7.83 (1H, s, Triazole), 8.15 (1H,

d, J = 8.8 Hz, ArH); 13

C NMR (100.6 MHz, CDCl3): δ 13.02 (-CH2CH3), 14.43 (C-4

CH3), 20.72 (-CH2CH3), 53.01 (-CH2N), 62.07 (-CH), 68.32 (-OCH2), 69.25 (-OCH2Ph),

101.23 (C-8), 105.20 (ArC), 112.08 (C-6), 114.68 (C-10), 120.79 (C-3), 121.81, 124.56,

125.04 (3ArC), 125.19 (C-5), 125.04, 125.40, 125.46 (3ArC), 126.38 (CH=C), 127.39,

134.38 (2-ArC), 143.99 (CH=C), 145.89 (C-4), 153.23 (C-9), 153.72 (ArC), 159.88 (C-

7), 161.95 (CO); HR-ESI-TOF-MS m/z 486.2018 ([M+H]+), calcd for [C28H27N3O5+H]

+

486.2023.

2.10.4.25. 3-Hexyl-7-(2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74a)


, KBr): 3385,

2920, 2851, 1717, 1611, 1387, 1260, 1172, 1026 and 770 cm-1

cm-1

; 1H NMR (400 MHz,

CDCl3): δ 0.89 (3H, t, J = 7.0 Hz, -(CH2)5CH3), 1.25-1.40 (6H, m, -CH2CH2(CH2)3CH3),

1.46-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 7.3 Hz, -

CH2(CH2)4CH3), 4.02-4.09 (2H, m, -CH2N), 4.47-4.59 (2H, m, -CH & -OCHα), 4.72 (1H,

dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.19 (2H, s, -CH2OPh), 6.78 (1H, d, J = 2.9 Hz, C-8H),

6.83 (1H, dd, J = 8.8 & 1.5 Hz, C-6H), 6.94-6.96 (3H, m, ArH), 7.25-7.30 (2H, t, J = 8.8

Hz, ArH), 7.47 (1H, d, J = 8.7 Hz, C-5H), 7.79 (1H, s, triazole H); 13

C NMR (100.6

MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.79 (C-4 CH3), 21.46 (-CH2(CH2)3CH2CH3),

22.59 (-CH2(CH2)3CH2CH3), 28.74 (-CH2CH2(CH2)3CH3), 29.35 (-CH2CH2(CH2)3CH3),

31.66 (-(CH2)3CH2CH2CH3), 53.00 (-CH2N), 61.66 (-CH), 68.38 (-OCH2), 69.27 (-

OCH2Ph), 101.35 (C-8), 111.48 (C-6,C-10), 112.11 (2ArC), 115.52 (ArC), 122.09 (C-3),


125

124.52 (C-5), 125.52 (CH=C), 129.21 (2ArC), 139.59 (CH=C), 146.02 (C-4), 153.33 (C-

9), 158.09 (ArC), 159.92 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 492.2493 ([M+H]+),


492.2493.

2.10.4.26. 3-Hexyl-7-(2-hydroxy-3-(4-(2-chlorophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3392,

2926, 2872, 1718, 1617, 1458, 1280, 1170, 1087 and 759 cm-1

; 1H NMR (400 MHz,


1.45-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, d, J = 7.3 Hz, -

CH2(CH2)4CH3), 3.75 (1H, brs, OH), 4.04-4.09 (2H, m, -CH2N), 4.53-4.60 (2H, m, -CH

& -OCHα), 4.74 (1H, dd, J = 13.2 & 2.2 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.76 (1H, d,

J = 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.8 & 2.2 Hz, C-6H), 6.87-7.34 (4H, m, ArH), 7.47


C NMR (100.6MHz, CDCl3): δ

14.03 (-(CH2)5CH3), 14.77 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.46 (-


(-(CH2)3CH2CH2CH3), 53.03 (-CH2N), 62.97 (-CH), 68.29 (-OCH2), 69.23 (-OCH2Ph),

101.23 (C-8), 112.13 (C-6), 114.07 (C-10), 114.73, 122.03, 122.92 (3ArC), 123.97 (C-3),

124.70 (C-5), 125.48 (CH=C), 127.74 (2ArC), 130.24 (CH=C), 146.06 (C-4), 153.27 (C-

9), 153.54 (ArC), 159.92 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 526.2109 ([M+H]+),

calcd for [C28H32ClN3O5+H]+

526.2103.




, KBr): 3393,

2927, 2855, 1705, 1616, 1383, 1298, 1159, 1087 and 768 cm-1

; 1H NMR (400 MHz,


1.46-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, d, J = 7.7 Hz, -


& -OCHα), 4.73 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.16 (2H, s, -CH2OPh), 6.76-6.95

(5H, m, C-6H, C-8H & ArH), 7.15 (1H, t,J = 8.1 Hz, ArH), 7.48 (1H, d, J = 8.8 Hz, C-


126

5H), 7.81 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3),

14.81 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.49 (-CH2(CH2)3CH2CH3), 28.72 (-

CH2CH2(CH2)3CH3), 29.34 (-(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.99

(-CH2N), 61.89 (-CH), 68.37 (-OCH2), 69.24 (-OCH2Ph), 101.31 (C-8), 112.08 (C-6),

114.03 (C-10), 112.97, 115.24, 121.44 (3ArC), 124.10 (C-3), 124.65 (C-5), 125.53

(CH=C), 130.26, 134.84 (2ArC), 143.39 (CH=C), 146.01 (C-4), 153.31 (C-9), 158.75 (C-

7), 159.85 (ArC), 162.06 (CO); HR-ESI-TOF-MS m/z 526.2106 ([M+H]+), calcd for

[C28H32ClN3O5+H]+

526.2103.




, KBr): 3392,

2922, 2853, 1718, 1611, 1387, 1250, 1091 and 825 cm-1


0.88 (3H, t, J = 7.3 Hz, -(CH2)5CH3), 1.23-1.40 (6H, m, -CH2CH2(CH2)3CH3), 1.45-1.54

(2H, m, -CH2CH2(CH2)3CH3), 2.37 (3H, s, C-4 CH3), 2.61 (2H, t, J = 7.3 Hz, -


& -OCHα), 4.74 (1H, dd, J = 13.9 & 2.2 Hz, -OCHβ), 5.15 (2H, s, -CH2OPh), 6.75 (1H, d,

J = 2.9 Hz, C-8H), 6.81 (1H, dd, J = 9.5 & 2.9 Hz, C-6H), 6.85-6.89 (2H, m, ArH), 7.17-

7.21 (2H, m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13

C NMR

(100.5 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.81 (C-4 CH3), 22.59 (-

CH2(CH2)3CH2CH3), 27.49 (-CH2(CH2)3CH2CH3), 28.72 (-CH2CH2(CH2)3CH3), 29.35 (-

(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.98 (-CH2N), 61.96 (-CH), 68.36

(-OCH2), 69.26 (-OCH2Ph), 101.31 (C-8), 112.08 (C-6), 114.84 (C-10), 115.99, 124.12

(3ArC), 124.62 (C-3), 125.53 (C-5), 126.13 (CH=C), 129.33 (2ArC), 143.56 (CH=C),

146.02 (ArC), 153.31 (C-4), 156.63 (C-9), 159.84 (C-7), 162.06 (CO); HR-ESI-TOF-MS

m/z 526.2103 ([M+H]+), calcd for [C28H32ClN3O5+H]

+ 526.2103.

2.10.4.29. 3-Hexyl-7-(2-hydroxy-3-(4-(2-bromophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3232,

2925, 2853, 1718, 1621, 1487, 1297, 1170, 1087 and 757 cm-1

; 1H NMR (400 MHz,


127




& -OCHα), 4.73 (1H, dd, J = 13.2 & 2.9 Hz, -OCHβ), 5.26 (2H, s, -CH2OPh), 6.77 (1H,

d, J = 2.9 Hz, C-8H), 6.81-6.86 (2H, m, C-6H, ArH), 7.03 (1H, dd, J = 8.1 & 1.5 Hz,

ArH), 7.21-7.27 (1H, m, ArH), 7.46-7.51(2H, m, ArH and C-5H), 7.86 (1H, s triazole H);

13C NMR (100.6 MHz, CDCl3): δ 14.04 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.58 (-



101.30 (C-8), 112.09 (C-6, ArC), 112.23 (C-10), 113.89 (ArC), 114.81 (C-3), 122.54

(ArC), 124.08 (C-5), 124.61 (CH=C), 125.52, 128.52 (2ArC), 133.32 (CH=C), 145.99

(C-4), 153.32 (C-9), 154.40 (ArC), 159.87 (C-7), 162.04 (CO); HR-ESI-TOF-MS m/z

570.1603 ([M+H]+), calcd for [C28H32BrN3O5+H]

+ 570.1598.

2.10.4.30. 3-Hexyl-7-(2-hydroxy-3-(4-(4-bromophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3402, 2922,

2855, 1717, 1610, 1387, 1251, 1171, 1091 and 823 cm-1




CH2(CH2)4CH3), 3.76 (1H, d, J = 4.4 Hz,OH), 4.02-4.09 (2H, m, -CH2N), 4.50-4.59 (2H,


6.75 (1H, d, J = 2.9 Hz, C-8H), 6.80-6.85 (3H, m, C-6H, ArH), 7.33-7.36 (2H, m, ArH),


C NMR (100.6 MHz, CDCl3):

δ 14.03 (-(CH2)5CH3), 14.79 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.46 (-



113.42 (C-10), 114.76, 116.46 (3ArC), 123.99 (C-3), 124.70 (C-5), 125.50 (CH=C),

132.22 (2ArC), 143.41 (CH=C), 146.09 (C-4), 153.24 (C-9), 157.10 (ArC), 159.86 (C-7),


128

162.08 (CO); HR-ESI-TOF-MS m/z 570.1598 ([M+H]+), calcd for [C28H32BrN3O5+H]

+

570.1598.

2.10.4.31. 3-Hexyl-7-(2-hydroxy-3-(4-(2-nitrophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3419,

2924, 2856, 1689, 1612, 1347, 1255, 1163, 1090 and 739 cm-1

; 1H NMR (400 MHz,



2.61 (2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 4.01-4.10 (2H, m, -CH2N), 4.22-4.30 (1H, m, -


5.35 (2H, s, -CH2OPh), 5.64 (1H, d, J = 5.12 Hz, OH), 6.93-6.96 (2H, m, C-6H, C-8H),

7.09-7.14 (1H, m, ArH), 7.57-7.70 (3H, m, ArH), 7.85 (1H, d, J = 8.1 Hz, C-5H), 8.21

(1H, s, triazole H); 13

C NMR (100.6 MHz, DMSO-d6): δ 14.01 (-(CH2)5CH3), 14.68 (C-4

CH3), 22.13 (-CH2(CH2)3CH2CH3), 26.86 (-CH2CH2(CH2)3CH3), 28.71 (-


(-OCH2), 70.10 (-OCH2Ph), 101.04 (C-8), 112.38 (C-6), 113.92 (C-10), 115.61, 120.95

(2ArC), 122.65 (C-3), 124.99 (C-5), 125.99 (ArC), 126.39 (CH=C), 134.38, 139.77

(2ArC), 141.56 (CH=C), 146.76 (C-4), 150.66 (C-9), 153.08 (ArC), 160.44 (C-7), 161.01

(CO); HR-ESI-TOF-MS m/z 537.2346 ([M+H]+), calcd for [C28H32N4O7+H]

+ 537.2344.

2.10.4.32. 3-Hexyl-7-(2-hydroxy-3-(4-(3-nitrophenoxy)methyl)-1,2,3-triazol-1-

yl)propoxy)-4-methylcoumarin (74h)


, KBr): 3222,

2928, 2858, 1717, 1618, 1349, 1252, 1162, 1083 and 826 cm-1

; 1H NMR (400 MHz,




4.45 (1H, dd, J = 13.2 & 3.7 Hz, -OCHα), 4.61 (1H, dd, J = 13.8 & 3.2 Hz, -OCHβ), 5.29

(2H, s, -CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.93-6.96 (2H, m, C-8H, C-6H), 7.49-

7.69 (3H, m, ArH), 7.80-7.87 (2H, m, ArH, C-5H), 8.25 (1H, s, triazole H); 13

C NMR


129

(100.6 MHz, DMSO-d6): δ 13.94 (-(CH2)5CH3), 14.62 (C-4 CH3), 22.05 (-



101.01 (C-8), 109.06 (C-6), 112.18 (C-10), 113.87, 115.76, 122.17 (3ArC), 122.61 (C-3),

125.91 (C-5), 126.31 (CH=C), 130.66 (ArC), 141.68 (CH=C), 146.64 (C-4), 148.69

(ArC), 153.02 (C-9), 158.55 (C-7), 160.37 (ArC), 160.90 (CO); HR-ESI-TOF-MS m/z

537.2336 ([M+H]+), calcd for [C28H32N4O7+H]

+ 537.2344.

2.10.4.33. 3-Hexyl-7-(2-hydroxy-3-(4-(4-nitrophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3367,

2929, 2856, 1699, 1610, 1382, 1256, 1173, 1003 and 834 cm-1

; 1H NMR (400 MHz,




4.48 (1H, dd, J = 13.9 & 7.3 Hz, -OCHα), 4.63 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.32

(2H, s, -CH2OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.93-6.96 (2H, m, C-6H, C-8H), 7.24-

7.27 (2H, m, ArH), 7.67 (1H, d, J = 8.8 Hz, C-5H), 8.18-8.22 (2H, m, ArH), 8.27 (1H, s,

triazole H); 13

C NMR (100.6 MHz, DMSO-d6): δ 13.95 (-(CH2)5CH3), 14.61 (C-4 CH3),

22.07 (-CH2(CH2)3CH2CH3), 26.81 (-CH2CH2(CH2)3CH3), 28.66 (-


(-OCH2), 70.07 (-OCH2Ph), 101.02 (C-8), 112.28 (C-6), 113.88 (C-10), 115.20 (2ArC),

122.62 (C-3), 125.83 (2ArC), 126.05 (C-5), 126.32 (CH=C), 140.99 (ArC), 141.43

(CH=C), 146.65 (C-4), 153.02 (C-9), 160.38 (C-7), 160.92 (ArC), 163.31 (CO); HR-ESI-

TOF-MS m/z 537.2341 ([M+H]+), calcd for [C28H32N4O7+H]

+ 537.2344.

2.10.4.34. 3-Hexyl-7-(2-hydroxy-3-(4-(o-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74j)


, KBr): 3385,

2922, 2852, 1716, 1611, 1387, 1250, 1121, 1025 and 748 cm-1

; 1H NMR (400 MHz,



130

1.45-1.52 (2H, m, -CH2CH2(CH2)3CH3), 2.18 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.61

(2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 3.87 (1H, d, J = 5.1 Hz, OH), 4.05-4.09 (2H, m, -

CH2N), 4.54-4.60 (2H, m, -CH & -OCHα), 4.71 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ), 5.19

(2H, s, -CH2OPh), 6.75-6.92 (4H, m, C-6H, C-8H & ArH), 7.10-7.15 (2H, m, ArH), 7.47



14.04 (-(CH2)5CH3), 14.79 (Ph-CH3), 16.19 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3),

27.49 (-CH2CH2(CH2)3CH3), 28.66 (-(CH2)2CH2(CH2)2CH3), 31.65 (-

(CH2)3CH2CH2CH3), 53.00 (-CH2N), 61.59 (-CH), 68.32 (-OCH2), 69.26 (-OCH2Ph),

101.29 (C-8), 111.44 (C-6), 112.66 (ArC), 114.82 (C-10), 120.95 (ArC), 124.09 (C-3),

124.28 (C-5), 125.52, 126.87(2ArC), 126.87 (CH=C), 130.75 (ArC), 144.49 (CH=C),

146.00 (C-4), 153.32 (C-9), 156.22 (ArC), 159.89 (C-7), 162.06 (CO); HR-ESI-TOF-MS

m/z 506.2653 ([M+H]+), calcd for [C29H35N3O5+H]

+ 506.2649.

2.10.4.35. 3-Hexyl-7-(2-hydroxy-3-(4-(m-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74k)


, KBr): 3511, 2924,

2852, 1718, 1610, 1385, 1259, 1173, 1085 and 777 cm-1



(2H, m, -CH2CH2(CH2)3CH3), 2.31 (Ph-CH3), 2.36 (3H, s, C-4 CH3), 2.61 (2H, t, J = 8.1

Hz -CH2(CH2)4CH3), 3.77 (d, 1H, J = 5.1 Hz, OH), 4.03-4.09 (2H, m, -CH2N), 4.53-4.58


CH2OPh), 6.74-6.85 (5H, m, C-6H, C-8H, ArH), 7.11-7.16 (1H, m, ArH), 7.47 (1H, d, J

= 8.7 Hz, C-5H), 7.79 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.03 (-

(CH2)5CH3), 14.78 (C-4 CH3), 21.44 (Ph-CH3), 22.57 (-CH2(CH2)3CH2CH3), 27.47 (-



112.11 (ArC), 114.75 (C-10), 115.48, 122.07 (2ArC), 123.99 (C-3), 124.54 (C-5), 125.48

(CH=C), 129.18, 139.55 (2ArC), 144.01 (CH=C), 146.04 (C-4), 153.29 (C-9), 158.06 (C-

7), 159.91 (ArC), 162.07 (CO); HR-ESI-TOF-MS m/z 506.2651 ([M+H]+), calcd for

[C28H35N3O5+H]+

506.2649.


131

2.10.4.41. 3-hexyl-7-(2-hydroxy-3-(4-(p-tolyloxymethyl)-1,2,3-triazol-1-

yl)propyloxy)-4-methylcoumarin (74l)


, KBr): 3386,

2920, 2852, 1721, 1610, 1383, 1247, 1176, 1089 and 831 cm-1

; 1H NMR (400 MHz,


1.45-1.54 (2H, m, -CH2CH2(CH2)3CH3), 2.27 (3H, s, Ph-CH3) 2.36 (3H, s, C-4 CH3),

2.61 (2H, t, J = 8.1 Hz, -CH2(CH2)4CH3), 3.85 (1H, d, J = 5.1 Hz, OH), 4.03-4.10 (2H,

m, -CH2N), 4.49-4.58 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 13.9 & 3.7 Hz, -OCHβ),

5.14 (2H, s, -CH2OPh), 6.75-6.86 (4H, m, C-6H, C-8H & ArH), 7.03-7.07 (2H, m, ArH),


C NMR (100.6 MHZ, CDCl3):

δ 14.04 (-(CH2)5CH3), 14.79 (C-4 CH3), 20.41 (Ph-CH3), 22.59 (-CH2(CH2)3CH2CH3),


(CH2)3CH2CH2CH3), 52.97 (-CH2N), 61.85 (-CH), 68.39 (-OCH2), 69.25 (-OCH2Ph),

101.36 (C-8), 112.07 (C-6), 114.53 (2ArC), 114.81 (C-10), 124.08 (C-3), 124.49 (C-5),

125.51 (CH=C), 129.91, 130.52 (3ArC), 144.15 (CH=C), 145.98 (C-4), 153.33 (C-9),

155.96 (ArC), 159.89 (C-7), 162.05 (CO); HR-ESI-TOF-MS m/z 506.2647 ([M+H]+),


506.2649.

2.10.4.36. 3-Hexyl-7-(2-hydroxy-3-(4-(2-methoxyphenoxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (74m)


, KBr): 3411, 2924,

2854, 1694, 1608, 1385, 1255, 1124, 1087 and 736 cm-1




CH2(CH2)4CH3), 3.83 (4H, m, Ph-OCH3, OH), 4.01-4.05 (2H, m, -CH2N), 4.45-4.55 (2H,


6.76-7.04 (6H, m, C-8H, C-6H & ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.83 (1H, s,

triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.80 (C-4 CH3),


(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 52.94 (-CH2N), 55.75 (Ph-OCH3),


132

62.87 (-CH), 68.40 (-OCH2), 69.22 (-OCH2Ph), 101.35 (C-8), 112.04 (C-6, ArC), 114.31

(C-10), 114.80, 120.81, 121.89 (3ArC), 124.08 (C-3), 124.76 (C-5), 125.50 (CH=C),

144.08 (CH=C), 145.95 (C-4), 147.45, 149.52 (2ArC), 153.33 (C-9), 159.89 (C-7),


+

522.2599.

2.10.4.37. 3-Hexyl-7-(2-hydroxy-3-(4-((3-methoxyphenoxy)methyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (74n)


, KBr): 3222, 2923,

2853, 1715, 1609, 1301, 1201, 1160, 1051 and 783 cm-1




CH2(CH2)4CH3), 3.76-3.79 ( 4H, m, OH, Ph-OCH3), 4.03-4.10 (2H, m, -CH2N), 4.53-

4.59 (2H, m, -CH & -OCHα), 4.72 (1H, dd, J = 12.4 & 2.2 Hz, -OCHβ), 5.16 (2H, s, -

CH2OPh), 6.51-6.57 (3H, m, C-6H, C-8H & ArH), 6.76-6.85 (2H, m, ArH), 7.13-7.18

(1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); 13

C NMR (100.6

MHz, CDCl3): δ 14.03 (-(CH2)5CH3), 14.78 (C-4 CH3), 22.57 (-CH2(CH2)3CH2CH3),


(CH2)3CH2CH2CH3), 52.98 (-CH2N), 55.20 (Ph-OCH3), 61.69 (-CH), 68.34 (-OCH2),

69.24 (-OCH2Ph), 101.19 (ArC), 106.65 (C-8), 106.83, 112.08 (2ArC), 114.77 (C-6),

124.02 (C-10), 124.59 (C-3), 125.49 (C-5), 129.91 (CH=C), 143.81 (ArC), 146.03

(CH=C), 153.29 (C-4), 159.27 (C-9), 159.88 (C-7), 160.72 (2ArC), 162.07 (CO); HR-

ESI-TOF-MS m/z 522.2593 ([M+H]+), calcd for [C29H35N3O6+H]

+ 522.2599.

2.10.4.38. 3-Hexyl-7-(2-hydroxy-3-(4-((2-iodophenoxy)methyl)-1,2,3-triazol-1-


It was obtained as white solid in 83 % yeld; m. p 168-173 °C; IR (cm-1

, KBr): 3285,

2924, 2855, 1717, 1618, 1333, 1297, 1169, 1086 and 761 cm-1

; 1H NMR (400 MHz,




133

CH2(CH2)4CH3), 3.78 (1H, d, J = 5.2 Hz, OH), 4.03-4.08 (2H, m, -CH2N), 4.54-4.63 (1H,


6.69-6.96 (4H, m, C-6H, C-8H & ArH), 7.25-7.30 (1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz,

C-5H), 7.71-7.73 (1H, m, ArH), 7.89 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3):

δ 14.06 (-(CH2)5CH3), 14.82 (C-4 CH3), 22.59 (-CH2(CH2)3CH2CH3), 27.51 (-


(-CH2N), 63.40 (-CH), 68.39 (-OCH2), 69.15 (-OCH2Ph), 86.60 (ArC), 101.35 (C-8),

112.09 (C-6), 112.73 (C-10), 114.85, 123.18 (2ArC), 124.13 (C-3), 124.62 (C-5), 129.55

(CH=C), 125.55, 139.38 (2ArC), 143.96 (CH=C), 145.97 (C-4), 153.34 (C-9), 156.59

(C-7), 159.87 (ArC), 161.03 (CO); HR-ESI-TOF-MS m/z 618.1475 ([M+H]+), calcd for

[C28H32IN3O5+H]+

1459.

2.10.4.39. 3-Hexyl-7-(2-hydroxy-3-(4-(4-iodophenoxy)methyl)-1,2,3-triazol-1-



, KBr): 3384,

2922, 2852, 1717, 1611, 1386, 1249, 1175, 1096 and 841 cm-1

; 1H NMR (400 MHz,





(4H, m, C-6H, C-8H & ArH), 7.46-7.53 (3H, m, ArH, C-5H), 7.80 (1H, s, triazole H);

13C NMR (100.6 MHz, CDCl3): δ 14.05 (-(CH2)5CH3), 14.83 (C-4 CH3), 22.58 (-



83.45 (ArC), 101.24 (C-8), 112.12 (C-6), 112.77 (C-10), 117.03 (2ArC), 124.02 (C-3),

124.70 (C-5), 125.51 (CH=C), 138.19 (2ArC), 143.39 (CH=C), 146.09 (C-4), 153.24 (C-

9), 157.87 (ArC), 159.85 (C-7), 162.08 (CO);HR-ESI-TOF-MS m/z 618.1459 ([M+H]+),

calcd for [C28H32IN3O5+H]+

618.1459.

2.10.4.40. 3-Hexyl-7-(2-hydroxy-3-(4-(3-fluorophenoxymethyl)-1,2,3-triazol-1-



134


, KBr): 3404,

2931, 2858, 1702, 1615, 1335, 1287, 1158, 1087 and 844 cm-1

; 1H NMR (400 MHz,



CH2(CH2)4CH3), 3.78 (1H, d, J = 5.12 Hz, OH), 4.00-4.07 (2H, m, -CH2N), 4.48-4.58


CH2OPh), 6.61-6.84 (5H, m, C-6H, C-8H & ArH), 7.16-7.23 (1H, m, ArH), 7.47 (1H, d,

J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.05 (-


29.35 (-(CH2)2CH2(CH2)2CH3), 31.63 (-(CH2)3CH2CH2CH3), 52.97 (-CH2N), 61.96 (-

CH), 68.39 (-OCH2), 69.23 (-OCH2Ph), 101.34 (ArC), 102.46 (C-8), 102.71, 107.99

(2ArC), 108.21 (C-6), 110.29 (C-10), 112.06 (C-3), 114.87 (C-5), 124.14 (CH=C),

124.63 (ArC), 125.54 (CH=C), 130.33 (C-4), 143.49 (C-9), 145.99 (C-7), 153.33, 159.85

(2ArC), 162.05 (CO); HR-ESI-TOF-MS m/z 510.2393 ([M+H]+), calcd for

[C28H32FN3O5+H]+

510.2399.

2.10.4.41. 3-Hexyl-7-(2-hydroxy-3-(4-(4-fluorophenoxymethyl)-1,2,3-triazol-1-



, KBr): 3413,

2932, 2859, 1702, 1615, 1355, 1216, 1158, 1087 and 829 cm-1

; 1H NMR (400 MHz,



CH2(CH2)4CH3), 3.84 (1H, d, J = 4.4 Hz, OH), 4.03-4.10 (2H, m, -CH2N), 4.50-4.60


CH2OPh), 6.75-6.97 (6H, m, C-6H, C-8H & ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.81

(1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.02 (-(CH2)5CH3), 14.77 (C-4

CH3), 22.56 (-CH2(CH2)3CH2CH3), 27.45 (-CH2CH2(CH2)3CH3), 29.31 (-


(-OCH2), 69.25 (-OCH2Ph), 101.23 (C-8), 112.12 (C-6), 114.75 (C-10), 115.69, 115.78,

115.92 (4ArC), 123.99 (C-3), 124.64 (C-5), 125.49 (CH=C), 143.67 (CH=C), 146.09 (C-


135

4), 153.25 (C-9), 154.09, 156.21 (2ArC), 159.87 (C-7), 162.09 (CO); HR-ESI-TOF-MS

m/z 510.2399 ([M+H]+), calcd for [C28H32FN3O5+H]

+ 510.2399.

2.10.4.42. 3-Hexyl-7-(2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-triazol-1-



, KBr): 3421,

2925, 2856, 1707, 1609, 1387, 1251, 1085 and 761 cm-1






(2H, m, C-6H, C-8H), 7.01-7.04 (2H, m, ArH), 7.29-7.53 (8H, m, C-5H, ArH), 7.83 (1H,

s, triazole H); 13

C NMR (100.6 MHZ, CDCl3): δ 14.03 (-(CH2)5CH3), 14.74 (C-4CH3),



(-OCH2), 69.27 (-OCH2Ph), 101.30 (C-8), 112.06 (C-6), 114.78 (C-10), 114.95, 124.02

(3ArC), 124.02 (C-3), 124.64 (C-5), 125.49, 126.59 (3ArC), 126.71 (CH=C), 128.08,

128.67, 134.22, 140.41 (6ArC), 143.85 (CH=C), 146.02 (C-4), 153.29 (C-9), 157.59

(ArC), 159.88 (C-7), 162.06 (CO); HR-ESI-TOF-MS m/z 568.2804 ([M+H]+), calcd for

[C34H37N3O5+H]+ 568.2806.

2.10.4.43. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-2-yloxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (74t)


, KBr): 3161,

2925, 2856, 1718, 1621, 1390, 1294, 1161, 1084 and 845 cm-1

; 1H NMR (400 MHz,





(2H, m, C-6H, C-8H), 7.12-7.23 (2H, m, ArH), 7.32-7.75 (6H, m, C-5H, ArH), 7.83 (1H,

s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.03 (-(CH2)5CH3), 14.71 (C-4 CH3),


136



(-OCH2), 69.27 (-OCH2Ph), 101.23 (C-8), 107.02 (ArC), 112.05 (C-6), 114.69 (C-10),

118.59 (ArC), 123.81 (C-3), 123.81, 123.93 (3ArC), 124.69 (C-5), 125.44, 126.38,

126.78 (3ArC), 127.51 (CH=C), 129.03, 129.45, 134.25 (3ArC), 143.70 (CH=C), 146.02

(C-4), 153.23 (C-9), 155.93 (ArC), 159.87 (C-7), 162.05 (CO); HR-ESI-TOF-MS m/z

542.2649 ([M+H]+), calcd for [C32H35N3O5+H]

+ 542.2649.

2.10.4.44. 3-Hexyl-7-(2-hydroxy-3-(4-(naphthalen-1-yloxymethyl)-1,2,3-triazol-

1-yl)propyloxy)-4-methylcoumarin (74u)


, KBr): 3384,

2923, 2853, 1716, 1610, 1395, 1271, 1104, 1021 and 766 cm-1

; 1H NMR (400 MHz,





(2H, m, C-6H, C-8H), 6.91 (1H, d, J = 7.3 Hz, ArH), 7.31-7.48 (5H, m, ArH), 7.76 (1H,

d, J = 8.1 Hz, C-5H), 7.86 (1H, s, triazole H); 13

C NMR (100.6 MHz, CDCl3): δ 14.05 (-


29.34 (-(CH2)2CH2(CH2)2CH3), 31.65 (-(CH2)3CH2CH2CH3), 53.00 (-CH2N), 62.12 (-

CH), 68.36 (-OCH2), 69.25 (-OCH2Ph), 101.28 (C-8), 105.24 (ArC), 112.04 (C-6),

114.77 (C-10), 120.82 (ArC), 121.83 (C-3), 124.03, 124.52 (2ArC), 125.21 (C-5),

125.45, 125.48, 125.70 (3ArC), 126.39 (CH=C), 127.42, 134.42 (2ArC), 144.67 (CH=C),

146.00 (C-4), 153.29 (C-9), 155.75 (ArC), 159.86 (C-7), 162.05 (CO);HR-ESI-TOF-MS

m/z 542.2652 ([M+H]+), calcd for [C32H35N3O5+H]

+542.2649


137

2.11. Experimental details of antifungal activity

Antifungal activity assay

The anti-A. fumigatus, A. niger and A. flavus activity of all the compounds was studied by

disc diffusion and microbroth dilution assays.66

Anti Aspergillus activity assays

Disc diffusion assay

The disc diffusion test was performedin radiation sterilized Petri plates of 10.0

cmdiameter (Tarsons, Kolkata, India). Different concentrations ranging from 750 to 1.46

μg of the test compounds were impregnated on the sterilized disc (5.0 mm in diameter) of

Whatman filter paper No. 1. The discs were placed on the surface of the agar plates

already inoculated with A. fumigates, A. niger or A. flavus spores. The plates were

incubated at 37 oC and examined at 24, 48 and 96 h for zone of inhibition, if any, around

the disc. The concentration, which developed the zone of inhibition of at least 6.0 mm

diameter, was considered as minimum inhibitory concentration.

Microbroth dilution assay

The test was performed in 96 well culture plates (Nunc, Nunclon). Various

concentrations of synthetic compounds in the range of 1000-3.1μg/ml were prepared in

the wells by two-fold dilution method. Amphotericin B (1) was used as a standard drug

for comparison. Assay was performed as per standard method described by Dabur et al.67


138

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