Chapter-1

Recent synthetic developments of Povarov

Reaction and 2,3-dihydroquinazolinone

derivatives: A short review

Chapter-1

1

1.1 Introduction

Heterocyclic chemistry is a very important branch of organic chemistry accounting

for about one-third of contemporary publications. Indeed, two thirds of organic

compounds are heterocyclic compounds. Nitrogen, oxygen and sulfur are the most

common heteroatoms but heterocyclic rings containing other hetero atoms are too

widely recognized. An enormous number of heterocyclic compounds are known and

this number is increasing rapidly day to day. In addition, these compounds also

comply with the general rule proposed by Huckel. They are highly distributed in

natural products and present as a major components in biological molecules.

The rich activity of heterocyclic compounds in biological systems is important for

pharmaceuticals, and they provide a platform for the rapid exchange of research in the

areas of pharmaceutical, medicinal, and organic chemistry. Over 75% of the top two

hundred branded drugs in the pharmaceutical industry have heterocyclic fragments in

their structures. N-containing family of more than 12,000 natural products includes

molecules of a wide ranging (Figure 1) expanse of structural diversity,[1] among the

heterocycles found in nature, nitrogen containing heterocycles are the most abundant

due to their wide distribution in nucleic acids. This illustrate their involvement in

almost every physiological process of plants and creatures.

Figure-1 Natural alkaloids

Chapter-1

2

1.2. Short literature review on Povarov reaction

Quinolines rings are present in a number of natural products and synthetic

pharmaceuticals. Because of its wide spread biological activities, many methods have

been developed for the synthesis of quinolines, the classic methods includes Doebner-

Miller reaction, Combes synthesis, Conrad Limpach synthesis, Bischler-Napieralski

synthesis, Friedlander synthesis and Povarov reaction etc.

The [4+2] cycloaddition reaction of N-aryl imines with nucleophilic olefins is one of

the most desirable methods of quinoline preparation, quinolines can be easily held by

using Lewis acids. BF3-OEt2 has been mainly applied for this purpose since the

revolutionary works of Povarov.[2] Acid-mediated cycloaddition between the

azadiene moieties of N-aryl imines and dienophiles also has turn an established route

to various tetrahydroquinolines and consequently, quinolines, the major class of

heterocycles. Hence, this interaction between N-aryl imines and electron-rich

dienophiles (Scheme 1) should be placed as the Povarov reaction.

Today, these types of Diels−Alder reactions are valuable synthetic routes in organic

synthesis, generating heterocyclic rings where the size of the second ring depends on

chain broadening. Indeed, multi-component inter and intramolecular Povarov

reactions have gained popularity in both diversity-oriented synthesis and target

oriented synthesis.

Scheme-1

Chapter-1

3

The reaction mechanism for the Povarov reaction to the quinoline is represented in

Scheme 2, initially aniline and benzaldehyde react to form imine. The Povarov

reaction requires a lewis acid such as boron trifluoride to activate the imine for an

electrophilic addition of the activated alkene. This reaction step forms an oxonium ion

which then reacts with the aromatic ring in a electrophilic aromatic substitution, two

steps of additional elimination reactions forms the quinoline ring.

Scheme-2 Mechanism of povarov reaction.

This short review covers the literature, but does not intend to be strictly complete,

although its goal is to highlight the improvements in the synthesis of quinoline

derivatives via the Povarov reaction.

1.2.1 Lewis acid catalyzed multicomponent povarov reaction

Numerous approaches have been reported in the literature using Lewis acid catalyst

for the synthesis of 2-aryl quinoline derivatives. BF3-OEt2 is well known acid catalyst,

by using this catalyst many protocols are reported. It has many advantages like mild

reaction conditions, easy work-up, a wide range of substrate applicability, and

products in good yields.

Chapter-1

4

D. J. Dibble and co workers[3] reported poly quinolines by using schiff base with

acetylene by using lewis acid catalyst with phenylacetylene in the presence of a

Lewis acid mediator and the sacrificial oxidant chloranil (Scheme 3).

Scheme-3

C. D. Smith and group[4] reported tetrahydroquinoline by using anilines and

benzaldehydes, with different norbornenes with high diversity in a multicomponent

fashion and are obtained in good yield with high diastereoselectivity (Scheme 4).

NH2 R2

HO

BF3.OEt220 mol%

R1

R3

CH2Cl245 0C

NH

H

H

R2

R3

R1

Scheme-4

Carmindo Ribeiro Borel et al.[5] reported 2-(2-pyridyl)quinolines was achieved via a

multi component Povarov reaction of aromatic aldehydes, anilines, and ethyl vinyl

ether under boron trifluoride methyl etherate, it shows several advantages over

previous reported methods (Scheme 5).

Scheme-5

Diego R. Merchan and co workers[6] reported 6,7-methylendioxy-

tetrahydroquinolines, by using iso eugenol as a alkene with aromatic aldehydes and

Chapter-1

5

anilines in presence of Lewis acid catalyst, racemic products are formed in moderate

to good yields (Scheme 6).

Scheme-6

Alexey V. Tarantin et al.[7] developed synthesis of 3-ethoxy-carbonyl-5-isopropyl-9-

methoxy carbonyl-9,12a-dimethyl-7,8,8a,9,10,11,12,12a-octahydronaphtho [1,2 f]

quinoline by using iminoglyoxylate with ethyl vinyl ether in the presence of 15 mol%

BF3·OEt2 with moderate diastereoselectively (Scheme 7).

Scheme-7

Vladimir V. Kouznetsov et al. developed a synthesis of tetrahydro quinolines[8] by

using aniline, benzaldehyde and in presence of trans anithole as a alkene source by

using lewis acid catalyst BF3·OEt2. New different substituted tetrahydroquinolines are

reported from the trans anithole under supercritical fluid (CO2) conditions has been

reported (Scheme 8).

Chapter-1

6

Scheme-8

1.2.2 Chiral phosphoric acid catalysed povarov reaction

Chiral phosphoric acid (Figure 1) is one among the best catalyst which is using in

synthesis of quinolines and it is having so many advantages like stereo selectivity,

catalytic amount is enough to carry out reaction effectively.

Figure-2 R= C6H4Cl, tri-isopropyl phenyl, 1-napthyl,

G. Dagousset and co workers[9] reported, chiral phosphoric acid catalyzed three-

component Povarov reactions using enethioureas as dienophile. Different functional

bearing aromatic and aliphatic aldehydes, as well as anilines, were tolerated in this

catalytic multicomponent reaction, leading to hexahydropyrrolo [3,2-c] quinolines in

high yields with excellent diastereo and enantioselectivities (Scheme 9).

Scheme-9

Chapter-1

7

G. Dagousset et al. developed[10] three-component Povarov reaction of aldehydes,

anilines, and enecarbamates by using chiral phosphoric acid as a catalyst, this

reaction afforded cis-4-amino-2-aryl(alkyl)-1,2,3,4-tetrahydroquinolines in high

yields with excellent diastereo selectivities and absolute enantioselectivities (Scheme

10).

Scheme-10

Hua Liu et al. developed an approach[11] which combines the advantages of both

MCRs and organocatalysis, most important is the highly efficient synthesis of

enantiomerically pure (2,4-cis)-4-amino2-aryl(alkyl)-tetrahydroquinolines. Its

application has led to the development of a short, efficient synthesis of torcetrapib

(Scheme 11).

NH2 R1

HO

R CH2Cl2, 0 0C NH

0.1 equivalentchiral phosphoric acid

R1

R

CbzHN NHCbz

Scheme-11

Giulia Bergonzini and coworkers developed[12] an asymmetric Povarov reaction of N-

arylimines with 2- and 3-vinylindoles has been developed using a chiral phosphoric

acid ((S)-TRIP) as a catalyst. This method makes a versatile synthetic platform for the

construction of enantio enriched compounds containing an indole moiety, a very

common structure in natural and bioactive molecules (Scheme 12).

Chapter-1

8

Scheme-12

Hong-Hao Zhang et al. developed a first catalytic asymmetric Povarov[13] reaction of

isatin containing 2-azadienes with 3-vinylindoles was reported in the presence of

chiral phosphoric acid, which tolerates a wide range of substrates with generally

excellent diastereoselectivity and good enantioselectivity (Scheme 13).

NN

O

R2

R1

NH

NH

NH

1-napthyl Chirolphosphoric acid 35 mol %

NO

R2

R1

R

R

O-xylene, 45 0C,

Scheme-13

1.2.3 Transition and inner transition metal triflates catalysed povarov reaction.

Ala Bunescu and co workers developed[14] a two-step synthesis of 2-acyl-

tetrahydroquinoline, through three-component reaction of α-oxo aldehydes, anilines

and dienes, by using yetribium triflate as catalyst yields tetrahydro quinolines in good

yield (Scheme 14).

Scheme-14

Chapter-1

9

Courtney E. Meyet and co workers[15] reported a alkyl substituted quinolines from

anilines, aldehydes, and alkynes. Copper (II) triflate catalyzes this three-component

coupling reaction without cocatalyst. Both electron-rich and electron-poor anilines

react efficiently in these three-component reaction (Scheme 15).

Scheme-15

Heather Twin et al. synthesized pyrrolo[3,4]quinolines[16] through the coupling of

anilines with propargylic substituted heterocyclic aldehydes in the presence of metal

triflates (Dy(OTf)3). This reaction proceeds through formation of imine and a formal

intramolecular aza Diels−Alder reaction. This approach was utilized in a total

synthesis of quinoline alkaloids (Scheme 16).

Scheme-16

Mingsheng Xie et al. reported[17] asymmetric Povarov reaction catalyzed by an N,N’-

dioxide L4–Sc(OTf)3 complex, wide variety of N-aryl aldimines and α-alkyl styrenes

were tolerated in this reaction, and the products are in good yields with excellent

diastereo and enantioselectivities (Scheme 17).

Chapter-1

10

Scheme-17

1.2.4 Iodine catalysed povarov reaction

Qinghe Gao and group[18] reported highly efficient iodine-mediated formal [3+2+1]

cycloaddition for the direct synthesis of substituted quinolines using acetophenones,

arylamines, and styrenes has been developed. This synthetic pathway represents an

interesting new form of reactivity for the Povarov reaction. This autotandem catalytic

process promote three mechanistically distinct reactions in a one pot using molecular

iodine (Scheme 18).

Scheme-18

Xiang-Shan Wang et al.[19] have showed that a facile method to synthesize exo-

tetrahydroindolo[3,2-c]quinoline derivatives in a three component reaction between

an aromatic aldehyde, a reactive amine, and an indole, with iodine as catalyst. The

advantages of this method include mild reaction conditions, moderate yields, high

stereoselectivity, metal-free catalyst, and operational simplicity (Scheme 19).

Chapter-1

11

Scheme-19 1.2.5 Acid catalysed povarov reaction

Yu-Long Zhao et al. described[20] a proficient synthetic method for 4-((1,3-dithian-2-

ylidene)methyl)quinolines, mediated by trifluoromethanesulfonic acid, ethynyl

ketene-S,S-acetals can react with various arylamines and aldehydes gives

corresponding quinoline derivatives in high yields through arylimine formation, and

the products are regiospecific (Scheme 20).

Scheme-20

Jing Sun and co workers have showed,[21] three-component reaction of aromatic

aldehydes, arylamines and methyl propiolates, mediated by p-toluenesulfonic acid.

This acid catalyst efficiently established the imino Diels–Alder reaction with β-

enamino ester as dienophile. This reaction provides a suitable and stereoselective

procedure for the preparation of 2-aryl-4-arylamino-1,2,3,4-tetrahydroquinoline-3-

carboxylates in satisfactory yields (Scheme 21).

Chapter-1

12

Scheme-21

1.2.6 Radical cation catalysed povarov reaction.

Xiaodong Jia and group[22] reported a domino process between iminoethyl glyoxylate

and N-vinylamides was achieved by using catalytic radical cation salt induced

conditions producing a series of quinoline-2-carboxylates. N-Vinylamides were

involved as an acetylene equivalent (Scheme 22).

Scheme-22

Yaxin Wang et al. describd[23] an efficient synthesis of quinoline-fused lactones and

lactams using a radical cation salt-prompted sp3 C−H aerobic oxidation. The catalytic

aerobic oxidation of glycine esters and amides was screened for a broad range of

substrates. This approach provides one-step access to these biologically and

synthetically relevant core structures from simple starting materials (Scheme 23).

Scheme-23

Chapter-1

13

1.2.7 Microwave assisted povarov reaction

Abhijit R. Kulkarni have showed that[24] efficient and speedy microwave-assisted

synthesis of cyclopentadiene ring-fused tetrahydroquinolines using multi-component

Povarov reaction catalyzed by indium(III)chloride. This protocol has so many

advantages like shorter reaction time with high yields (Scheme 24).

Scheme-24

1.2.8 Montmorillonite as a catalyst

Hans-Georg Imrich et al. asssembled[25] a three-component reaction between a nitro-

benzene, different substituted aldehyde, and a dienophile in the presence of iron

powder as a reductant and montmorillonite K10 as a catalyst in aqueous citric acid

condition undergo Povarov reaction with high stereo-selectivity (Scheme 25).

Scheme-25

Sankar K. Guchhait have reported[26] a novel HClO4-modified montmorillonite-

promoted Povarov reaction, then aerobic dehydrogenation to provide the synthesis of

polysubstituted quinolines. HClO4-modified montmorillonite as a privileged catalyst,

advantages of this method are potential use for promoting povarov reactions and

possible successive aerobic dehydrogenation (Scheme 26).

Chapter-1

14

Scheme-26

1.2.9 Post transition Metal chlorides as catalyst

Vellaisamy Sridharan et al. developed[27] a new domino reaction that involves the

creation of two C–C bonds and the generation of two stereocenters, one of them

quaternary, with complete diastereoselectivity and in a single synthetic operation.

This transformation can be considered as a novel type of vinylogous aza-Povarov

reaction, and establishes the foremost example of an α, β-unsaturated hydrazone

behaving as the dienophile component in an aza Diels–Alder reaction (Scheme 27).

Scheme-27

Vladimir V. Kouznetsov and group showed[28] that general protocol for the simple and

efficient BiCl3-catalyzed synthesis of 2-alkyl-1,2,3,4-tetrahydroquinolines. Synthetic

protocols described the one-pot preparation of these tetrahydroquinolines using ali-

phatic aldehydes, anilines and N-vinyl acetamide in the multicomponent condensation

reaction (Scheme 28).

Chapter-1

15

Scheme-28

1.2.10 Intramolecular povarov reaction

Ming Chen and coworkers developed[29] a facile indeno [1,2-b] quinolines by using

Povarov reaction through intramolecular cyclisation. Reactions proceeded efficiently

in the absence of oxidants, aromatization was achieved by elimination of a leaving

group. A broad kind of substitutes may well be incorporated, that permits for a

convenient structural modification of straightforward indenoquinolines (Scheme 29).

Scheme-29

1.3. Short literature review on synthetic efferts of 2,3-dihydroquinazolinones

1.3.1 Acid catalysed synthesis

Vilas B. Labade et al. developed[30] an efficient synthetic route for 2,3-

dihydroquinazolin-4(1H)-ones using 2-morpholinoethanesulfonic acid as a new

organocatalyst. The developed synthetic protocol represents a completely unique and

extremely easy route for the preparation of 2,3-dihydroquinazolin-4(1H)-one

derivatives. Additionally, the microwave irradiation technique is with success

enforced for ending the reactions in shorter reaction times (Scheme 30).

Chapter-1

16

Scheme-30

B. V. Subba Reddy and co workers assembled[31] a condensation of 2-

aminobenzamide with aldehydes or ketones has been achieved using cellulosesulfonic

acid under mild reaction conditions to furnish 2,3-dihydroquinazolin-4(1H)-ones in

good yields with a high selectivity. The usage of solid acid catalyst makes this

methodology quite straightforward (Scheme 31).

Scheme-31

1.3.2 Amberlyst-15 mediated synthesis

P. VNS Murthy et al.[32] reported economical and clear technique for the synthesis of

2-aryl 2,3-dihydroquinazolin-4(1H)-ones exploitation amberlyst-15 as a recyclable

catalyst. A variety of dihydroquinazolinones were prepared from 2-aminobenzamide

and aldehydes under beneath gentle conditions in excellent yields (Scheme 32).

Scheme-32

1.3.3 Base mediated synthesis

Xiao-Feng Wu and group[33] developed an remarkable and convenient procedure for

2,3-dihydroquinazolin-4(1H)-ones synthesis. Inexpensive inorganic base was applied

Chapter-1

17

as a promoter and water was used as a green solvent for this transformation (Scheme

33).

NH2

O

Ph HNH

NH

O

Ph

K3PO4,H2O, 100 0C, 8 hCN

Scheme-33

1.3.4 Chiral phosphoric acid catalysed asymmetric synthesis

Figure-3 R= 9-anthracenyl, 2,4,6-(i-Pr)3C6H2

Dao-Juan Cheng showed[34] that for the first time, an efficient catalytic asymmetric

synthesis of aminal containing heterocyclic compounds from imines. In the presence

of 10 mol% of a commercially available (Figure 2) chiral phosphoric acid, a range of

aromatic, α, β-unsaturated, and aliphatic imines react with 2-aminobenzamides to

grant dihydroquinazolinones in excellent yields (Scheme 34).

NH2

O

NH2

N

Ph H NH

NH

O

PhCHCl3, rt, 24 h

Catalyst (10 mol%)X

Scheme-34

Magnus Rueping report on the development[35] of a replacement metal-free, extremely

enantioselective, Bronsted acid catalyzed condensation reaction for the synthesis of

2,3-dihydroquinazolinones starting from readily available starting materials. Thus, a

highly extremely economical and general approach to valuable enantiomerically

Chapter-1

18

enriched 2,3-dihydroquinazolinones with preference for the more active S

enantiomers has been established (Scheme 35).

Scheme-35

Yan Jiang and co workers established[36] the enantioselective synthesis of various

substituted Spiro [indoline-3,20-quinazolines]. More significantly, this protocol not

solely takes into consideration the speedy building of the chiral Spiro [indoline-3,20-

quinazoline] design with potential applications in medicinal chemistry, however

additionally provides enantioselective Spiro [indoline-3,20-quinazoline] derivatives

for more structural modification and bioassay (Scheme 36).

Scheme-36

1.3.5 Click reaction

Ahmad Shaabani and co workers developed[37] an efficient condensation reaction of

2-aminobenzamide with various alkyl, aryl, and alicyclic aldehydes or ketones, that

provides 2,3-dihydroquinazolin-4(1H)-one derivatives in good yields. This reaction

will be classified as a brand new click synthesis as a result this reaction takes place in

short times (Scheme 37).

Chapter-1

19

Scheme-37

1.3.6 Intramolecular Pinner/Dimroth Rearrangement

Jian-Hong Tang et al. [38] reported the synthesis of quinazolin-4(3H)-one derivatives,

these are obtained by the cyclization of o-aminonitriles with carbonyl compounds

using zinc chloride as catalyst by exploitation DMF as a solvent. The reaction scope

is significant, and a number of aryl aldehydes could be successfully applied to react

with O-aminonitriles to provide quinazolinone compounds with excellent yields

(Scheme 38).

NH2

O

R3 HNH

NH

O

R3

CNR2

R1

DMF, ZnCl2

reflux

R2

R1

Scheme-38

1.3.7 Co-CNTs as a green reaction medium and a catalyst

Javad Safari and group assembled[39] the importance of quinazolinone analogues as

synthons in organic synthesis, they have reported the synthesis of a number of these

compounds through the Co-CNT catalyzed heterocyclization of O-aminobenzamide

with different aldehydes. Short reaction times, mildness, easy work-up are the benefits

of this protocol (Scheme 39).

Scheme-39

Chapter-1

20

1.3.8 Ionic liquid mediated synthesis

Jiuxi Chen et al. have been synthesized[40] 2,3-dihydroquinazolin-4(1H)-ones in high

yields through one-pot three-component cyclocondensation of isatoic anhydrides,

ammonia acetate and aldehydes in ionic liquid water solvent system while not the

utilization of any further catalyst (Scheme 40).

Scheme-40

Junke Wang and group[41] reported poly(4-vinylpyridine) supported acidic ionic liquid

catalyst, and employed in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones

underneath supersonic irradiation. Effective convalescent and reusability of the

catalyst square measure the a number of the benefits of this methodology. Most

significantly, the utilization of supersonic irradiation will clearly speed up the reaction

(Scheme 41).

Scheme-41

1.3.9 Using low valent Titanium

Daqing Shi reported a short[42] and facile synthesis of 1,2-dihydroquinazolin-4(3H)-

ones via the novel reductive cyclization of O-nitrobenzamides and aldehydes or

ketones promoted by TiCl4/Zn, benefits of this protocol area unit simply accessible

starting materials, convenient operation and moderate to good yields (Scheme 42).

Chapter-1

21

Scheme-42

1.3.10 Using metal triflates

Muthuraj Prakash et al.[43] developed metal catalysed 2,3-dihydroquinazolinones

enantioselective synthesis through intramolecular amidation of imines in excellent

yields. The scandium(III)-inda-pybox catalyst provided exceptional catalytic

activation of 2-amino N-phenylbenzamide to afford the corresponding 2,3-

dihydroquinazolinone with excellent enantioselectivity (Scheme 43).

Scheme-43

1.3.11 By reductive cyclisation

Yu Hu et al.[44] reported a series of 10-H-spiro[indoline-3,20-quinazoline]-2,40(30H)-

diones were synthesized by the reaction of 2-nitrobenzamides with isatins

respectively, mediate by SnCl2-2H2O system. A kind of substrates can participate in

the process with moderate to good yields (Scheme 44).

Chapter-1

22

Scheme-44

1.3.12 Nanoparticles used as recoverable catalyst

Amin Rostami and cluster[45] reported MNPs-PSA as a eco-friendly, efficient and

magnetically recoverable catalyst was used in synthesis of 2,3-dihydroquinazolin-

4(1H)-ones by direct cyclocondensation of anthranilamide and aryl aldehydes or

ketones with sensible to high yields in water, benefits of this catalyst are speedy,

simple and efficient separation by using an appropriate external magnet (Scheme 45).

Scheme-45

M. Z. Kassaee have assembled[46] Al/Al2O3 NPs as an effective catalyst in the one-

pot multicomponent synthesis of 2,3-dihydroquinazolin-4(1H)-ones. This catalyst is

very economical, simply offered, operationally straightforward, and needs gentle

reaction conditions. Conjointly the product were got in good yields with short reaction

times (Scheme 46).

Scheme-46

Chapter-1

23

1.3.13 Supramolecular synthesis

K. Ramesh and group showed an eco-friendly method[47] to synthesize 2,3-

dihydroquinazolin-4(1H)-ones in excellent yields, beneath neutral conditions in one-

pot involving catalysis by β-cyclodextrin in water. Catalyst can be recovered and

reused with a little loss of catalytic activity (Scheme 47).

NH2

O

NH2

CHO

NH

NH

O

R R

-CD/H2O

55-60 0C

Scheme-47

1.3.14 Grinding under Solvent-Free Conditions

Quan-Sheng Ding and group[48] have demonstrated a light and economical eco-

friendly synthesis of 2,3-dihydroquinazolin-4(1H)-ones underneath solvent-free

conditions, using citric acid as a novel organoacid green promoter, which uses neither

harsh conditions nor the use of hazardous catalysts and reagents. Notable benifits of

this protocol are wide substrates scope, short interval, inexpensive, water-solubility

organoacid, and high yields (Scheme 48).

Scheme-48

1.3.15 Ruthenium-catalysed oxidative synthesis.

Andrew J. A.Watson reported Ruthenium-catalysed oxidative synthesis[49] for the

conversion of alcohols into 2,3-dihydroquinazolines. Reaction conditions are 2-

aminobenzamide and alcohol, with crotononitrile, in presence of Ru(PPh3)3(CO)(H2)

Chapter-1

24

permits for the selective formation quinazolinones, and also the product in good

yields (Scheme 49).

Scheme-49

1.3.16 Miscelanious

Moni Sharma et al. developed[50] an efficient cyanuric chloride (2,4,6-trichloro-1,3,5-

triazine, TCT) catalyzed approach for the synthesis of 2,3-dihydroquinazolin-4(1H)-

one, 2-spiroquinazolinone, and glycoconjugates of 2,3-dihydro- quinazolin-4(1H)-one

derivatives. The reaction permits fast cyclization (8−20 min) with 10 mol % cyanuric

chloride to give skeletal complexity in excellent yield (Scheme 50).

Scheme-50

Matthieu Desroses reported[51] an simple easy and efficient protocol for the synthesis

of 2,3-dihydroquinazolinones. This technique, using T3P® as the catalyst, has several

advantages such as a easy operational procedure, a short reaction time, the

employment of very gentle conditions and a simple access to the compounds in good

yields (Scheme 51).

Chapter-1

25

Scheme-51

Someshwar D. Dindulkarwe and group[52] have successfully created a cost-effective

protocol for the synthesis of 2,3-dihydroquinazolin-4 (1H) -ones victimization CAN-

SiO2 as a fast reusable catalyst at room temperature. Compare to the earliest known

methodologies, this method offers several advantages, together with high production

of products, short reaction times, the recyclability of the catalyst (Scheme 52).

Scheme-52

Rong Zhang Qiao et al. reported[53] 2-substituted 2,3 dihydro quinazolinones in high

yields by condensation of anthranyl amides with aldehydes or ketones in the refluxing

2,2,2-trifluroethanol with none catalyst the gentle and neutral reaction conditions

permit the acid or base sensitive substrates to be involved in the reaction timescale

(Scheme 53).

Scheme-53

Chapter-1

26

1.4. Scope of the present work:

Recent days heterocyclic compounds have become an important source of discovery

of drug molecules. Particularly nitrogen containing heterocyclic ring play an

important role in bioorganic and medicinal chemistry, especially reports concerning

quinoline containing heterocyclic compounds have gradually increased because of

their potential biological activity and these quinolines are present in plants as

alkaloids best example is quinine and it is used as anti malarial drug by chinese and

indian ancient medicine.

2,3-dihydroquinazolinones containing heterocyclic compounds have got so much

importance because these quinazolinones are integral part of so many alakaloids and

these molecules are used as anticancer agents. Due to the biological significance of

these heterocycles so many synthetic efforts have been reported, during the course of

our research we have developed a new synthetic protocol for the synthesis of 2-aryl

quinoline and 2,3-dihydroquinazolinones derivatives.

Propylphosphonic anhydride (T3P®)-DMSO mediated one pot three component

synthesis of 2-aryl quinolines by modified povarov reaction provides 2-aryl

quinolines in a single step from benzyl alcohols, anilines and ethyl vinyl ether

mediated by T3P®-DMSO as shown in Scheme 83 and evaluated for their anticancer

activity against different human cancer cell lines. The results showed that compound

F16 was found to be most potent against human cancer cell lines at lower

concentrations.

Chapter-1

27

Scheme- 83

One-pot synthesis of 2, 3-dihydroquinazolin-4(1H)-ones from gem-

dibromomethylarenes using 2-aminobenzamide is described. Gem-

dibromomethylarenes used as aldehyde equivalent for the efficient synthesis of 2, 3-

dihydroquinazolin-4(1H)-ones, as shown in Scheme 101 and evaluated for their

anticancer activity against different human leukemic cell lines. The results showed

that compound F27 was found to be most potent against human cancer cell lines at

lower concentrations.

Where R1, R= H/Cl/Br/OMe.

Scheme-101

ZrO2-Al2O3 used as effective nano catalyst for the efficient synthesis of 2, 3-

dihydroquinazolin-4(1H)-ones from 2-aminobenzamide using benzaldehyde is

described, as shown in Scheme 119, we extended our work to synthesize biologically

active piperidine conjugated derivatives, the requisite title compounds F41-44 were

synthesized by the reaction of 6-chloro-2-(piperidin-4-yl)-2,3-dihydroquinazolin-

4(1H)-one with different benzene sulfonyl chlorides, benzoyl chlorides, benzyl

chlorides as shown in Scheme 120 and the product are obtained in good yields. Later

evaluated for their anticancer activity against different human cancer cell lines. The

results showed that compound F44 was found to be most potent against human cancer

cell lines at lower concentrations.

Chapter-1

28

NH

NH

O

R1

NH2

O

NH2

ZrO2-Al2O3 20 mol%

Ethanol, refluxR RR1-CHO

Scheme-119

Scheme-120

Chapter-1

29

References and Notes

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