CsF/Clinoptilolite: an Efficient Solid Base in SNAr · 2018. 8. 3. · 3 ! Abstract...

CsF/Clinoptilolite: an Efficient Solid Base in SNAr

and Copper-catalyzed Ullmann Reactions

Hoda Keipoura,b, Abolfazl Hosseinib, Amir Afsarib, Razieh Oladeeb,

Mohammad A. Khalilzadeh*b and Thierry Ollevier*a

a Département de chimie, Université Laval, 1045 avenue de la Médecine, Québec, QC, G1V 0A6, Canada

Fax: +14186567916; E-mail: [email protected]

b Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran

Fax: +981232211647; E-mail: [email protected]

2

Graphical Abstract

OH

R

X

EWG

DMSO, 110–115 °C0.1–5 h, X = F, Cl, BrCsF/Clinoptilolite

O

R EWG70–100%

R = H, Halogen, Alkyl, OMe, CN, NO2

O

R OMe72–91%

X

H(OMe)

DMSO, 120 °C14–16 hCsF/Clinoptilolite + CuO-np

3

Abstract

CsF/Clinoptilolite (CsF/CP) was found to be an efficient solid base catalyst for both SNAr and Ullmann ether

reactions. A general and efficient one-step procedure was developed for the synthesis of biaryl ethers via direct

coupling of electron-deficient aryl halides to phenols using CsF/CP. The protocol was also applied to electron-

rich aryl halides by addition of a catalytic amount of copper oxide nanoparticles. Both SNAr and Ullmann

reactions were rapid and provided good to excellent yields.

Keywords

Diaryl ethers, SNAr, Ullmann reaction, Heterogeneous catalyst, Clinoptilolite

Introduction

Zeolites are crystalline three-dimensional aluminosilicates with open channels or cages with molecular

dimensions.1 They are widely used as catalysts in chemical industries, in cracking, isomerization and alkylation

processes.2 Among those having synthetic and natural origin, natural zeolites are of great interest due to their

large scale availability and low prices. However, in spite of their availability, only a few representatives of this

class have been reported as solid supports in the field of organic synthesis.3 As a consequence of confined space

inside the porous structure, these materials are able to act as shape-selective nanoreactor,4 or host cavity for

various metals and small organic compounds. However, the latter is of great interest because the cation

encapsulation of a metal salt catalyst within a cavity might dramatically change its catalytic activity, leading to

unusual increased activity due to the effective cation scavenging. This is the key step, where the anion can act as

a Lewis base, accepting an acidic proton.5 Moreover, solid bases also have the advantages of nontoxicity, eco-

friendliness and easy work-up procedure.6 The importance of the fluoride ion as a catalyst for the promotion of

various types of base-catalyzed reactions in organic synthesis has been previously recognized.7 In particular, the

work of Miller revealed that the fluoride ion plays an important role in selected reactions because of its high

capability of hydrogen bond formation.8

4

Cesium fluoride (CsF) is an effective base in organic synthesis because the fluoride ion is largely unreactive

as a nucleophile.9 Removal of silicon groups (desilylation) is one of the major applications of CsF in the

laboratory, as its anhydrous nature allows clean formation of water-sensitive intermediates.10 It is exploited as

an efficient catalyst for the synthesis of o-diiodoarenes,11 carboxylic esters,12 trans-α-trifluoromethyl allylic

alcohols,13 γ-lactones,14 thioesters and thioethers15 and 3,4-dihydropyrimidine-2-(1H)-ones.16 In addition, it has

been used for SN-type aromatic substitution,17 Michael addition 18 and regio- and chemoselective ring opening of

epoxides with thiols,19 nucleophilic fluorination,20 selective triflation 21 and preparation of fluorinated

polymers.22 Although being an effective catalyst, it is not easy to handle this hygroscopic product and the

reproducibility of these reactions is invariably poor. Recently, poorly hygroscopic reagents generating fluoride

ions were designed allowing cesium fluoride to be absorbed on Celite,23 Al2O3 24 and CaO.25 Although there are

many reports on the use of solid bases in organic transformations,26 only a few examples involving SNAr

reactions have been reported.27 We recently developed a fluoride-catalyzed method for the formation of C–O

bonds between activated haloarenes and phenols.28 In our continued efforts for the development of solid base

catalysts for selective organic transformations, we wish to report herein our development of an improved

catalyst CsF/Clinoptilolite (CsF/CP) as a strong and poorly hygroscopic solid base in organic chemistry. In fact,

when phenol was reacted with 4-fluoronitrobenzene using CsF/CP in DMSO at 110 °C, the desired diaryl ether

was obtained in quantitative isolated yield in short reaction time (0.15 h). This was in agreement with the

tendency of clinoptilolite for cation absorption which was reported previously.29 This result led us to undertake a

survey of reaction variables to develop the optimum conditions for the transformation.

Results and Discussion

Effect of base amount on the coupling reaction

The efficiency of CsF/CP system was studied for the synthesis of 4-nitrophenyl phenyl ether with various

amounts of base (Table 1). At first, a model reaction was carried out in the absence of a base. The reaction of 1a

with 2a did not afford an appreciable amount of the desired 4-nitrophenyl phenyl ether in the absence of CsF

even after the extended time (8 h), whereas, 0.54 g of catalyst involving 60% (w/w) cesium fluoride, afforded

100% of conversion after 0.15 h (Table 1, entries 9 and 12). These findings revealed that the heterogeneous

catalyst exhibited high catalytic activity in the desired transformation. Control experiment with unsupported CsF

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(1 equiv.) at 110 °C showed quantitative conversion of 4-fluoronitrobenzene, albeit after a longer reaction time

(Table 1, entry 1). When the quantity of CsF/CP was reduced from 0.54 g (1 equiv.) to 0.45 g (0.83 equiv.), the

yield of the product remained unchanged. However, the required time was longer (Table 1, entry 11). Higher

quantity of CsF/CP did not have great influence on the outcome of the reaction (Table 1, entry 13).

Solvent and temperature effects on the coupling reaction

Some commercial solvents such as acetonitrile, toluene, dioxane, DMF and DMSO were examined (Table

1). We found that both solvents, DMSO (Table 1, entry 12) and DMF (Table 1, entry 6), are ideal for the

efficient and rapid coupling of phenol and 4-fluoronitrobenzene with comparable efficiency.

Effect of reaction temperature on the coupling reaction of 4-fluoronitrobenzene and phenol using CsF/CP

was studied. As expected, the reaction time was influenced by the temperature. It was found that by increasing

the reaction temperature, the conversion was increased favorably reaching its maximum at 110 °C, whereas,

increasing the reaction temperature to 120 °C had a little effect on the yield of the reaction. The reaction did not

proceed well at room temperature and gave only very poor yields.

Table 1 O-Arylation of Phenol with 4-Fluoronitrobenze: Optimization of the Reaction Conditionsa

<Table 1-Scheme>

Entry Base (g) Solvent t (h) T (°C) Yield (%)b 1 CsF (0.32 g) DMSO 8 110 100 2 CP (0.22 g) DMSO 8 110 <7 3 KF/CP (0.62 g) DMSO 0.5 110 100 4 CsF/CP (0.54 g) MeCN 5 110 78 5 CsF/CP (0.54 g) Toluene 5 110 75 6 CsF/CP (0.54 g) DMF 0.75 110 98 7 CsF/CP (0.54 g) Dioxane 4 110 45 8 CsF/CP (0.54 g) DMSO 1.30 90 100 9 CsF/CP (0.54 g) DMSO 0.15 120 100 10 CsF/CP (0.54 g)c DMSO 0.75 110 98 11 CsF/CP (0.45 g) DMSO 0.5 110 100 12 CsF/CP (0.54 g) DMSO 0.15 110 100 13 CsF/CP (0.65 g) DMSO 0.15 110 100

a Reaction conditions: Aryl–F (2 mmol), Phenol (2.1 mmol), Solvents (5–7 mL). b Average GC yields with n-octane as an internal standard calculated from at least two runs. c 2 mmol of phenol was used.

Catalytic activity of powdered CsF/CP with various CsF loadings

The CsF/CP samples were prepared with various loadings of CsF over the support, namely 4, 7.5, 9.5 and

10.5 mmol/g. The catalyst with a loading of 9.5 mmol/g displayed the highest activity compared with the other

catalysts, while the catalyst with a loading of 10.5 mmol/g showed almost equal activity in this reaction (Fig. 1).

6

The loss of activity observed above 9.5 mmol/g was possibly due to decreasing quantity of CsF in the CP

cavities or due to CsF aggregation, thus reducing the dispersion of CsF on the zeolite. The catalyst with a

loading of 9.5 mmol CsF/g Clinoptilolite [ca. 60% (w/w) CsF] was chosen for our studies.

<Insert Fig.1>

In our examination of the use of CsF/CP for the combination of electron-poor aryl halides with a variety of

phenol derivatives, it is clear that aryl halides substituted in the para position with electron-withdrawing groups

can be coupled with a wide diversity of phenols to give the desired product in good to excellent yields (see

Table 2). The fact that these activated aryl halides are particularly good substrates refers to charge stabilization

of the intermediate Meisenheimer complex formed during the reaction.30

Having established the optimal reaction conditions (CsF/CP 0.54 g, phenol 0.2 g (2.1 mmol) and 4-‐

fluoronitrobenzene 0.28 g (2 mmol) in DMSO), the protocol was extended to other aryl fluorides, chlorides and

bromides to verify scope and limitations of the method (Table 2). The coupling of the 4-‐fluoronitrobenzene with

moderately electron-deficient halophenols such as iodo-, bromo- and chlorophenols occurred in excellent yields

(Table 2, entries 1–9). Even sterically hindered ortho-substituted phenols reacted with 4-‐fluoronitrobenzene, and

the reaction proceeded smoothly to give the diaryl ethers in excellent yields (Table 2, entries 3, 6 and 7).

Similarly, sterically encumbered nucleophiles such as 2-tert-butylphenol, which is quite problematic as

coupling partners in SNAr reactions, reacted with 4-fluoronitrobenzene to give the corresponding diaryl ether in

a 98% yield (Table 2, entry 11). The reaction of sterically hindered 2,6-di-tert-butylphenol with 4-‐

fluoronitrobenzene using the standard base system produced no undesired products but the expected product in a

moderate yield and in longer reaction time (Table 2, entry 14). It should be noted that SNAr reactions of aryl

fluorides generally proceed readily with electron-rich phenols and sluggishly with electron-poor phenols. To our

surprise, using CsF/CP, even phenols bearing an electron-withdrawing group such as nitro and cyano could also

serve as efficient coupling partners (Table 2, entries 17–20).

A variety of substituted phenols were transformed into their corresponding ethers in good to excellent

isolated yields. The protocol tolerates functional groups like halides, methoxy, or carboxylic acid esters. An

aldehyde functional group on an aryl fluoride was also compatible under these conditions, although a slightly

lower yield was obtained in the reaction of 4-fluorobenzaldehyde with phenol (Table 2, entry 25). By routinely

7

running reactions in DMSO at 110 °C, we were able to couple electrophiles containing electron-withdrawing

groups other than nitro. Addition of phenols to aryl fluorides substituted with cyano, esters or formyl were also

feasible provided sufficient reaction times were allowed and a directing substitution pattern (para) employed

(entries 21–25). However, this protocol provided good yields only for electron-deficient aryl fluorides, chlorides

and bromides. Electron-neutral and electron-rich aryl halides were not active in our system and afforded only

poor yields.

Table 2 CsF/CP Promoted Coupling of Nitro Activated Aryl Fluorides with Phenols a

<Table 2-Scheme>

Entry Phenol Aryl halide Product Time (h) Yield (%)b

1 <Table 2-Entry 1> 0.15 95

2 <Table 2-Entry 2> 0.15 100

3 <Table 2-Entry 3> 0.15 100

4 <Table 2-Entry 4> 0.15 100

5 <Table 2-Entry 5> 0.15 100

6 <Table 2-Entry 6> 0.15 100

7 <Table 2-Entry 7> 3 100

8 <Table 2-Entry 8> 0.15 95

9 <Table 2-Entry 9> 0.15 95

10 <Table 2-Entry 10> 0.15 95

11 <Table 2-Entry 11> 0.75 98

12 <Table 2-Entry 12> 0.5 95

13 <Table 2-Entry 13> 0.15 95

14 <Table 2-Entry 14> 5 78

15 <Table 2-Entry 15> 0.15 100

16 <Table 2-Entry 16> 0.5 100

17 <Table 2-Entry 17> 0.75 80

8

18 <Table 2-Entry 18> 0.5 98

19 <Table 2-Entry 19> 0.75 98

20 <Table 2-Entry 20> 0.5 100

21 <Table 2-Entry 21> 0.5 92

22 <Table 2-Entry 22> 0.5 92

23 <Table 2-Entry 23> 2.5 88

24 <Table 2-Entry 24> 3.5 90

25 <Table 2-Entry 25> 2.5 85

26 <Table 2-Entry 26> 2.5 90

27 <Table 2-Entry 27> 2 85

a Reaction conditions: Aryl halide (2 mmol), phenol (2.1 mmol), CsF/CP (0.54 g), DMSO (5–7 mL). b Isolated yield.

Comparing superiority of CsF/CP over some previously reported protocols

A comparison of the present protocol with selected previously known protocols is collected in Table 3 to

demonstrate that the present protocol is indeed superior to several of them. Phenol is completely arylated in less

than 0.15 h at 110 °C in 100% isolated yield using the present protocol. Most of the other protocols listed

involve either longer time for completion or require prior preparation of the phenolic nucleophile or use

expensive materials with generally reduced isolated yields.

The present protocol is effective in affording complete arylation of 2-tert-butylphenol in less than 0.75 h.

The same transformation requires 9 h for completion using silylated phenol and proazaphosphatrane (Table 3,

entry 6). 4-tert-Butylphenol is arylated completely in less than 0.5 h using the present protocol. The use of

Bu4NBr/CsF is equally effective, however, it requires a long reaction time. Inspection of Table 2 reveals that

KF-based reagent gave marginally lower yields than the CsF counterpart with extended reaction times.31

Although this difference is small in general cases, it is more pronounced when comparing the coupling reaction

of sterically bulky nucleophiles such as 2,6-di-tert-butylphenol and 2,4,6-trichlorophenol with 4-

fluoronitrobenzene (Table 2, entries 7, 14 vs Table 3 entries 8, 9). Overall, the present methodology uses a cheap

and environmentally friendly heterogeneous catalyst and requires relatively shorter reaction times.

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Table 3 Comparison of Protocols for the O-arylation of Phenolic Nucleophiles with 4-Fluoronitrobenzene.

Solvent Temp. °C Base Yield (%) Time (h) Phenolic nucleophiles Entry

Acetone32 50 TBAF 92 24 Si(OPh)4 1 DMF33 100 Cs2CO3 92 1 PhOTBS 2 CH3CN27 Ref. KF/Al2O3/18-crown-6 98 1 Phenol 3 [Bmim]BF4

34 100 K2CO3 80 18 PhOMS 4 Solvent-free35 MW KF/Al2O3/Aliquat-336 92 0.15 Phenol 5 Toluene36 80 Proazaphosphatrane 99 9 2-t-Bu-PhOTBDMS 6 scCO2 (ca.21 MPa)37 90 Bu4NBr/CsF 97 16 4-tert-butylphenol 7 DMSO28 110-115 KF/CP 47 15 2,4,6-trichlorophenol 8 DMSO28 110-115 KF/CP 85 6 2,6-di-tert-butylphenol 9 DMSO 110 CsF/CP 100 0.15 Phenol 10 DMSO 110 CsF/CP 98 0.75 2-tert-butylphenol 11 DMSO 110 CsF/CP 95 0.5 4-tert-butylphenol 12

Reusability of the catalyst

We studied simple ways of recycling the CsF/CP solid base catalyst. The solid base was collected after the

reaction was completed. It was then filtered, washed thoroughly with ethyl acetate to extract the product and

dried at 80 °C in a vacuum drying oven. The activity of the base dropped significantly. The loss might be

attributed to the leaching of ionic species (Cs+, F−) from the catalyst into diaryl ether product mixture, which

was confirmed by flame atomic spectroscopy. An attempt was made to retain the ionic species of the catalyst

using vacuum distillation. The solvent of the reaction mixture was distilled off and the remaining solid was

washed thoroughly with dioxane to remove organic materials. The next run was performed by adding fresh

reactants to the recovered catalyst. Three consecutive reactions were performed in this manner retaining the

ionic species within the catalyst and the results are given in Table 4. The catalyst showed good recycling ability

with slight loss in activity.

Table 4 Recycling of CsF/CP Catalyst for the O-arylation of Phenol with 4-Fluoronitrobenzene.

Run Catalyst Conversion (%) 1 Fresh 100 2 Recycle-1 96 3 Recycle-2 94 4 Recycle-3 90 In continuation of our research work we were interested in the coupling reaction of phenols with unactivated

aryl halides. Copper-catalyzed Ullmann coupling of aryl halides with phenols represents the most popular

choice for the synthesis of diaryl ethers on laboratory and industrial scales.38 However, the utility of classical

Ullmann coupling has been greatly limited by harsh reaction conditions, for example, high temperatures,

stoichiometric use of copper compounds and low conversion of unactivated aryl halides.39 Although much effort

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has been devoted to developing more convenient methods of Ullmann-type O-arylation in recent years,

invention of mild, simple and low-cost methods are still highly desirable. Nanoparticles have emerged as robust

and high surface area heterogeneous catalysts,40 which serve as sustainable alternatives to conventional

materials, especially CuO nanoparticles due to their stability and wide availability.

Recently, CuO nanoparticle catalyzed C–N, C–O, and C–S cross-coupling reactions have been disclosed.41

Following successful application of CuO nanoparticles in phenol etherification, we wish to report a new system

in Ullmann type reaction catalyzed by CuO nanoparticles using CsF/CP as solid base. When the coupling

reaction of phenol with iodobenzene was performed in DMSO at 120 °C in the presence of CsF/CP under inert

atmosphere, the reaction proceeded to completion after 14 hours. Further investigation showed that the reaction

did not proceed at room temperature. Next, we extended our protocol to other phenol derivatives. The results are

summarized in Table 5. Our method compares well with other protocols used for the copper catalyzed Ullmann

reaction (Table 5, entry 1, yield of diphenylether: 91%; with CuBr, 97%;43a with CuI, 95%;43b with CuO,

87%;43c with α-Fe2O3@CuO 92%).43d

Copper nanoparticles were prepared according to a previously reported procedure.42 The morphology of the

CuO nanostructure was characterized by SEM and TEM techniques. Typical SEM micrograph of the CuO

nanoparticle is shown in Figure 2a. Results show the presence of CuO in nanosize. Figure 2b presents a typical

TEM image of CuO nanoparticles. Results show CuO nanoparticles with a diameter of about 25 nm.

<Insert Fig.2>

The absence of CsF/CP fails to generate the desired products and all the starting materials were recovered

from the reaction system. Decreasing the catalyst loading from 10 to 5 mol % resulted in a decrease of the yield

even under extended reaction time conditions. Moderate to excellent yields were obtained for substituted

phenols with both electron-donating and electron-withdrawing substituents (Table 5).

In general, the presence of electron-donating groups on phenols leads to higher yields than those with phenol

with electron-withdrawing groups. Interestingly, even phenols with more steric hindrance in the ortho position

were tolerated in this reaction (Table 5, entries 4, 6 and 8). The presence of an electron-donating group on the

iodo aryl partner did not have great influence on the outcome of the reaction (Table 5, entries 11 and 12).

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Table 5 Coupling Reaction of Aryl Halides with Phenols using CsF/CP in the Presence of CuO-np Catalyst a

Entry Phenols Aryl iodide Time (h)

Yield (%)b

1 <Table 5-Entry 1> <Table 5-Entry 1> 14 91




5 <Table 5-Entry 5> <Table 5-Entry 5> 14

91


82


78

8 <Table 5-Entry 8> <Table 5-Entry 8>

20

78


15

89

10

<Table 5-Entry 10> <Table 5-Entry 10> 15

90


15

87


15

85

Reaction conditions: a Phenol (0.75 mmol), CuO-np (10 mol %), Iodobenzene (0.5 mmol), CsF/CP (0.5 g) and DMSO (5 mL) at 120 ºC under N2. b Isolated yield.

A plausible mechanism of the copper-catalyzed reaction is shown in Scheme 1. As drawn, the catalytic cycle

maybe initiated by abstraction of a proton by a negatively charged fluoride moiety from the phenol to generate

the corresponding anion a stabilized on the cesium surface, which then attacked active species b to afford

intermediate c, where the positive charge developed may be distributed among the CuO nanoparticles present on

the surface of the nanoparticle cluster. Intermediate c may transform to free catalyst d by reductive elimination

providing the C–O cross coupled product followed by removal of hydrogen halide with CsF/CP.

Scheme 1 Proposed mechanism for CuO nanoparticles-catalyzed O-arylation of phenols with aryl halides

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Conclusion

We have prepared a nonhygroscopic solid base, CsF/CP, and employed it as an efficient base in the SNAr

and Ullmann coupling reactions of phenols with aryl halides. In comparison to cesium fluoride, CsF/CP is a

moisture stable base, which is prepared by a simple procedure and could be stored for extended periods of time

under air or in a desicator without noticeable deactivation. The reaction can be carried out under mild conditions

without any additives, affording the corresponding aryl ethers in good yields via SNAr reaction. CsF/CP also

enabled the Ullmann-type O-arylation of phenyl iodides to be performed cleanly. Overall, CsF/CP is a more

efficient solid base than our previously reported one (KF/CP).28 The use of CsF/CP as heterogeneous base in

other reactions is currently in progress in our laboratories.

Acknowledgments

The authors wish to thank the Islamic Azad University, Qaemshahr branch for funding this research, and the

Natural Sciences and Engineering Research Council of Canada (NSERC).

Experimental

General Remarks

The raw material was an Iranian commercial Clinoptilolite (Afrandtooska Company) from deposits in the

region of Semnan (very cheap, about 1$ per kg). All starting materials were used as purchased without further

purification. Reactions were performed under air atmosphere. Thin-layer chromatography (TLC) was performed

using on 60 mesh silica gel Merck TLC plates. Flash column chromatography was performed with Merck silica

gel (230–400 mesh). The yields reported are isolated yields and are the average of at least two runs. All values

were analyzed by using a HP GC 6890 that was equipped with a DB-5 CP column (30 m x 0.32 mm x 0.5 µm).

GC program parameters: injector 250 °C; flow 2 ml/min.; temperature program 40 °C/hold 2 min.; 280 °C/rate

10 °C per min./hold 5 min. Melting points were determined using an Electro thermal IA 9100 Digital Melting

Point apparatus and are uncorrected. NMR spectra were recorded on a Bruker AV-III-600 FT-NMR 600 MHz,

13

Bruker FT-NMR 400 MHz-Ultrashild and Bruker FT-NMR 300 MHz-Ultrashild spectrometer. NMR spectra

were obtained in CDCl3 and DMSO-d6.

Preparation of CsF/Clinoptilolite

Prepared by dissolving CsF (14.5 g) in distilled water (10 mL) and Clinoptilolite (10 g). The mixture was

stirred for 1 h then, the water was removed at 60–70 °C under reduced pressure (rotary evaporator). The

impregnated Clinoptilolite was further dried at 80 °C in a vacuum drying oven for 30 h. The hard, dry material,

thus obtained (24.5 g), was powdered with the help of a pestle and mortar. The resulting CsF/CP was kept in a

desiccator until required.

Typical Procedure A

Coupling of aryl fluorides with phenols in DMSO: A mixture of phenol (2.1 mmol), Aryl halide (2.0 mmol),

and 60% (w/w) cesium fluoride/Clinoptilolite [CsF/CP] (0.54 g) in DMSO (5–7 mL) was heated at 110 °C (bath

temperature). The mixture was stirred under air until the reaction was complete (monitored by TLC or GC). The

reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered. The resulting solution

was placed in a separating funnel and washed twice with water. The organic layer was dried with anhydrous

sodium sulfate, filtered, and concentrated in vacuo. The crude product was recrystallized in methanol to afford

the final product.

Typical Procedure B

A mixture of the phenol (0.75 mmol), aryl halide (0.5 mmol), CuO nanoparticles (10 mol %) and 60% (w/w)

CsF/CP (0.5 g) in dry DMSO (4 mL) was heated at 120 °C. The mixture was stirred under nitrogen atmosphere

until the reaction was complete (by TLC or GC monitoring). After completion, the reaction mixture was cooled

to room temperature, diluted with ethyl acetate, and filtered. The resulting solution was placed in a separatory

funnel and washed twice with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and

concentrated in vacuo. The crude products were purified by column chromatography on silica gel eluting with

ethyl acetate/hexane mixtures to afford the final product.

1-Fluoro-3-(4-nitrophenoxy)benzene (Table 2, entry 1).44 Prepared according procedure A, using 3-

fluorophenol (235 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in

DMSO (5 mL) at 110 °C. After 0.15 h, the crude product was recrystallized in methanol to afford the final

product (442 mg, 95% yield) as a colorless oil. 1H NMR (600 MHz, CDCl3): δ 8.24 (d, 3JHH = 9.0 Hz, 2H), 7.42

14

(dd, 3JHF = 8.4 Hz, 3JHH = 6.8 Hz, 1H), 7.09 (d, 3JHH = 9.0 Hz, 2H), 6.97 (dt, 3JHH = 6.8 Hz, 4JHF = 3.0 Hz, 1H),

6.89 (dd, 3JHF = 8.4 Hz, 4JHH = 2.4 Hz, 1H), 6.84 (td, 3JHH = 9.6 Hz, 4JHF = 2.4 Hz, 1H) ppm. 13C NMR (150

MHz, CDCl3): δ 164.6, 162.6 (d, 1JCF = 288 Hz), 156.6 (d, 3JCF = 36 Hz), 143.3, 131.4 (d, 3JCF = 36 Hz), 126.2,

117.9, 116.0 (d, 4JCF = 12 Hz), 112.4 (d, 2JCF = 96 Hz), 104.9 (d, 2JCF = 102 Hz) ppm.

1-Fluoro-4-(4-nitrophenoxy)benzene (Table 2, entry 2).45 Prepared according to procedure A, using 4-

fluorophenol (235 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in


product (466 mg, 100% yield) as a yellow solid. mp: 59 °C (litt.: 56–58 °C). 1H NMR (400 MHz, CDCl3): δ

8.18 (d, 3JHH = 9.2 Hz, 2H), 7.05-7.17 (m, 4H), 6.98 (d, 3JHH = 9.2 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ

163.4, 160.9, 159.3, 150.5 (d, 2JCF = 126 Hz), 143.3, 126.2, 122.4 (d, 3JCF = 36 Hz), 116.9 (t, 1JCF = 222 Hz)

ppm.

1-Chloro-2-(4-nitrophenoxy)benzene (Table 2, entry 3).28 Prepared according to procedure A, using 2-

chlorophenol (330 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in


product as a (499 mg, 100% yield) as a white solid. mp: 77 °C (litt.: 78–79 °C). 1H NMR (400 MHz, CDCl3): δ

8.19 (d, 3JHH = 8.9, 2H), 7.51 (dd, 3JHH = 8.0 Hz, 4JHH = 1.6 Hz, 1H), 7.33 (dt, 3JHH = 8.0 Hz, 4JHH = 1.6 Hz, 1H),

7.23 (dt, 3JHH = 8.0 Hz, 4JHH = 1.6 Hz, 1H), 7.16 (dd, 3JHH = 8.0 Hz, 4JHH = 1.6 Hz, 1H), 6.93 (d, 3JHH = 8.9 Hz,

2H) ppm.

1-Chloro-3-(4-nitrophenoxy)benzene (Table 2, entry 4).46 Prepared according to procedure A, using 3-



product (499 mg, 100% yield) as a white solid. mp: 60 °C (litt.: 60–62 °C). 1H NMR (600 MHz, CDCl3) δ: 8.24

(d, 3JHH = 9.6 Hz, 2H), 7.36 (dd, 3JHH = 8.4 Hz, 3JHH = 7.8 Hz, 1H), 7.24 (dd, 3JHH = 8.3 Hz, 4JHH = 1.8 Hz, 1H),

7.11 (dd, 4JHH = 2.4 Hz, 4JHH = 1.8 Hz, 1H), 7.05 (d, 3JHH = 9.6 Hz, 2H), 6.99 (dd, 3JHH = 8.3 Hz, 4JHH = 1.8 Hz,

1H) ppm. 13C NMR (150 MHz, CDCl3): δ 163.1, 156.3, 144.2, 136.1, 131.4, 126.2, 125.1, 121.3, 119.3, 118.5

ppm.

1-Fluoro-4-(4-nitrophenoxy)benzene (Table 2, entry 5).47 Prepared according to procedure A, using 4-


15


product (499 mg, 100% yield) as a white solid. mp: 76 °C (litt.: 76–78 °C). 1H NMR (400 MHz, CDCl3): δ 8.20

(dd, 3JHH = 7.0 Hz, 3JHH = 2.4 Hz, 2H), 7.38 (d, 3JHH = 7.0 Hz, 3JHH = 2.4 Hz, 2H), 6.92–7.13 (m, 4H) ppm.

2,4-Dichloro-1-(4-nitrophenoxy)benzene (Table 2, entry 6).28 Prepared according to procedure A, using 2,4-

dichlorophenol (342 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g)

in DMSO (5 mL) at 110 °C. After 0.15 h, the crude product was recrystallized in methanol to afford the final

product (568 mg, 100% yield) as a white solid. mp: 73 °C (litt.: 72–73 °C). 1H NMR (300 MHz, DMSO-d6): δ

8.25 (d, 3JHH = 9.1 Hz, 2H), 7.87 (d, 4JHH = 1.9 Hz, 1H), 7.56 (dd, 3JHH = 8.7 Hz, 4JHH = 1.9 Hz, 1H), 7.42 (d,

3JHH = 8.7 Hz, 1H), 7.13 (d, 3JHH = 9.1 Hz, 2H) ppm. 13C NMR (75 MHz, DMSO-d6): δ 162.2, 149.0, 143.1,

131.2, 131.0, 129.9, 127.4, 126.7, 125.0, 117.2 ppm.

1,3,5-Trichloro-2-(4-nitrophenoxy)benzene (Table 2, entry 7).28 Prepared according to procedure A, using

2,4,6-trichlorophenol (414 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP

(0.54 g) in DMSO (5 mL) at 110 °C. After 3 h, the crude product was recrystallized in methanol to afford the

final product (637 mg, 100% yield) as a yellow solid. mp: 94 °C (litt.: 93–95 °C). 1H NMR (300 MHz, DMSO-

d6): δ 8.24 (d, 3JHH = 8.9 Hz, 2H), 7.94 (s, 2H), 7.14 (d, 3JHH = 8.9 Hz, 2H) ppm. 13C NMR (75 MHz, DMSO-

d6): δ 161.0, 144.9, 143.4, 132.1, 130.2, 129.7, 126.8, 116.0 ppm.

1-Bromo-4-(4-nitrophenoxy)benzene (Table 2, entry 8).28 Prepared according to procedure A, using 4-

bromophenol (363 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g)


product (558 mg, 95% yield) as a light yellow solid. mp: 58 °C (litt.: 58–60 °C). 1H NMR (300 MHz, DMSO-

d6): δ 8.24 (d, 3JHH = 9.1 Hz, 2H), 7.65 (d, 3JHH = 8.7 Hz, 2H), 7.14 (d, 3JHH = 9.1 Hz, 4H) ppm. 13C NMR (75

MHz, DMSO-d6): δ 162.8, 154.2, 143.0, 133.8, 126.6, 123.1, 118.1, 117.9 ppm.

1-Iodo-4-(4-nitrophenoxy)benzene (Table 2, entry 9).48 Prepared according to procedure A, using 4-

iodophenol (462 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in


product (647 mg, 95% yield) as a yellow solid. mp: 51 ºC (litt.: 50–52 °C). 1H NMR (400 MHz, CDCl3): δ 8.22

16

(d, 3JHH = 9.2 Hz, 2H), 7.75 (d, 3JHH = 8.8 Hz, 2H), 7.04 (d, 3JHH = 9.2 Hz, 2H), 6.88 (d, 3JHH = 8.8 Hz, 2H) ppm.

13C NMR (100 MHz, CDCl3): δ 163.2, 155.0, 143.7, 139.4, 126.3, 123.2, 117.0, 89.4 ppm.

1-Methyl-4-(4-nitrophenoxy)benzene (Table 2, entry 10).28 Prepared according to procedure A, using 4-

methylphenol (227 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g)


product (435 mg, 95% yield) as an orange solid. mp: 69 °C (litt.: 69–70 °C). 1H NMR (300 MHz, DMSO-d6): δ

8.22 (d, 3JHH = 9.2 Hz, 2H), 7.28 (d, 3JHH = 8.2 Hz, 2H), 7.06 (d, 3JHH = 8.8 Hz, 4H), 2.33 (s, 3H) ppm. 13C NMR

(75 MHz, DMSO-d6): δ 163.7, 152.3, 142.4, 135.3, 131.3, 126.6, 120.9, 117.4, 20.8 ppm.

1-(tert-Butyl)-2-(4-nitrophenoxy)benzene (Table 2, entry 11).46 Prepared according to procedure A, using 2-

tert-butylphenol (315 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54

g) in DMSO (5 mL) at 110 °C. After 0.75 h, the crude product was recrystallized in methanol to afford the final

product (531 mg, 98% yield) as a white solid. mp: 106 °C (litt.: 105–107 °C). 1H NMR (400 MHz, CDCl3): δ

8.22 (d, 3JHH = 8.1 Hz, 2H), 7.49 (d, 3JHH = 7.8 Hz, 1H), 7.23 (m, 2H), 7.03 (d, 3JHH = 8.1 Hz, 2H), 6.91 (d, 3JHH

= 7.8 Hz, 1H), 1.41 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): 163.8, 153.6, 142.9, 142.2, 128.3, 127.6, 126.7,

125.7, 121.6, 117.6, 35.2, 30.1 ppm.

1-(tert-Butyl)-4-(4-nitrophenoxy)benzene (Table 2, entry 12).49 Prepared according to procedure A, using 4-

tert-butylphenol (315 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54


product (514 mg, 95% yield) as a white solid. 1H NMR (300 MHz, CDCl3): δ 8.18 (d, 3JHH = 9.3 Hz, 2H), 7.42

(d, 3JHH = 9.3 Hz, 2H), 7.02 (d, 3JHH = 2.7 Hz, 2H), 6.99 (d, 3JHH = 2.7 Hz, 2H), 1.35 (s, 9H) ppm.

1,3-Dimethyl-5-(4-nitrophenoxy)benzene (Table 2, entry 13).45 Prepared according to procedure A, using

3,5-dimethylphenol (256 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP

(0.54 g) in DMSO (5 mL) at 110 °C. After 0.5 h, the crude product was recrystallized in methanol to afford the

final product (461 mg, 95% yield) as a yellow solid. mp: 78 °C (litt.: 77–78 °C). 1H NMR (600 MHz, CDCl3): δ

8.2 (d, 3JHH = 9.6 Hz, 2H), 7.01 (d, 3JHH = 9.6 Hz, 2H), 6.9 (brs, 1H), 6.7 (brs, 2H), 2.3 (s, 6H) ppm. 13C NMR

(150 MHz, CDCl3): 163.8, 154.9, 140.3, 127.4, 125.9, 118.3, 117.2, 113.2, 21.9 ppm.

1,3-Di-tert-butyl-2-(4-nitrophenoxy)benzene (Table 2, entry 14).46 Prepared according to procedure A, using

2,6-di-tert-butylphenol (433 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP

17

(0.54 g) in DMSO (5 mL) at 110 °C. After 5 h, the crude product was recrystallized in methanol to afford the

final product (510 mg, 78% yield) as a yellow solid. mp: 107 °C (litt.: 106–108 °C). 1H NMR (400 MHz,

CDCl3): δ 8.2 (d, 3JHH = 9.2 Hz, 2H), 6.98 (d, 3JHH = 9.2 Hz, 2H), 6.92 (t, 3JHH = 8.8 Hz, 1H), 6.71 (d, 3JHH = 8.8

Hz, 2H), 2.06 (s, 18H) ppm. 13C NMR (CDCl3): δ 170.4, 164.5, 146.3, 144.2, 125.9, 121.9, 116.3, 116.2, 29.7,

21.0 ppm.

2-(4-Nitrophenoxy)naphthalene (Table 2, entry 15).28 Prepared according to procedure A, using 2-naphthol

(302 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5

mL) at 110 °C. After 0.15 h, the crude product was recrystallized in methanol to afford the final product (530

mg, 100% yield) as a red solid. mp: 97 °C (litt.: 98–99 °C). 1H NMR (600 MHz, CDCl3): δ 8.2 (d, 3JHH = 9.0 Hz,

2H), 7.94 (d, 3JHH = 9.0 Hz, 2H), 7.80 (d, 3JHH = 7.8 Hz, 1H), 7.57 (t, 3JHH = 7.8 Hz, 1H), 7.56 (m, 2H), 7.19 (d,

3JHH = 7.8 Hz, 1H), 7.03 (d, 3JHH = 8.1 Hz, 1H) ppm. 13C NMR (150 MHz, CDCl3): 164.1, 150.5, 142.8, 135.9,

128.8, 127.8, 127.1, 126.8, 126.3, 126.1, 126.0, 121.9, 116.9, 116.2 ppm.

1-Methoxy-4-(4-nitrophenoxy)benzene (Table 2, entry 16).46 Prepared according to procedure A, using 4-

methoxyphenol (260 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g)



(d, 3JHH = 8.7 Hz, 2H), 7.02 (d, 3JHH = 9.2 Hz, 2H), 6.99 (d, 3JHH = 8.7 Hz, 2H), 3.84 (s, 3H) ppm. 13C NMR (75

MHz, CDCl3): 164.2, 157.4, 148.2, 142.6, 126.2, 122.4, 116.4, 115.5, 60.1 ppm.

1-Nitro-2-(4-nitrophenoxy)benzene (Table 2, entry 17).47 Prepared according to procedure A, using 2-

nitrophenol (292 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in


product (416 mg, 80% yield) as a yellow solid. mp: 94 °C (litt.: 94–95 °C). 1H NMR (400 MHz, CDCl3): δ 8.26

(d, 3JHH = 9.6 Hz, 2H), 8.1 (d, 3JHH = 8.0 Hz, 1H), 7.71 (t, 3JHH = 8.0 Hz, 1H), 7.45 (t, 3JHH = 8.0 Hz, 1H), 7.26

(d, 3JHH = 8.0 Hz, 1H), 7.05 (d, 3JHH = 9.6 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ 162.0, 147.7, 143.4,

142.3, 134.9, 126.3, 126.1, 122.5, 117.1 ppm.

1-Nitro-3-(4-nitrophenoxy)benzene (Table 2, entry 18).50 Prepared according to procedure A, using 3-



18

product (509 mg, 98% yield) as a yellow solid. mp: 123 °C (litt.: 122–123 °C). 1H NMR (400 MHz, CDCl3): δ

8.3 (d, 3JHH = 9.2 Hz, 2H), 8.13 (dd, 3JHH = 8.4 Hz, 4JHH = 2.0 Hz, 1H), 7.96 (t, 4JHH = 2.0 Hz, 1H), 7.64 (t, 3JHH =

8.4 Hz, 1H), 7.46 (dd, 3JHH = 8.4 Hz, 4JHH = 2.0 Hz, 1H), 7.13 (d, 3JHH = 9.2 Hz, 2H) ppm. 13C NMR (100 MHz,

CDCl3): δ 161.5, 155.8, 131.0, 126.3, 126.0, 119.8, 118.2, 115.0 ppm.

4-(4-Nitrophenoxy)nitrobenzene (Table 2, entry 19).47 Prepared according to procedure A, using 4-



product (509 mg, 98% yield) as a yellow solid. mp: 145 ºC (litt.: 144–146 °C). 1H NMR (400 MHz, CDCl3): δ

8.15–8.25 (m, 4H), 7.09–7.18 (m, 4H) ppm.

4-(4-Nitrophenoxy)benzonitrile (Table 2, entry 20).46 Prepared according to procedure A, using 4-

cyanophenol (250 mg, 2.1 mmol), 4-fluoronitrobenzene (282 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in


product (480 mg, 100% yield) as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 8.29 (d, 3JHH = 9.4 Hz, 2H),

7.58 (d, 3JHH = 8.6 Hz, 2H), 7.05–7.14 (m, 4H) ppm. 13C NMR (75 MHz, CDCl3): δ 163.1, 160.2, 145.2, 135.8,

126.5, 120.2, 119.3, 118.5, 108.7 ppm.

4-Phenoxybenzonitrile (Table 2, entry 21).45 Prepared according to procedure A, using phenol (197 mg, 2.1

mmol), 4-fluorobenzonitrile (242 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5 mL) at 110 °C.

After 0.5 h, the crude product was recrystallized in methanol to afford the final product (358 mg, 92% yield) as

a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.51–7.63 (m 2H), 7.34–7.44 (m, 2H), 7.16–7.25 (m, 1H), 7.01–

7.09 (m, 2H), 6.93-6.99 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ 161.6, 154.9, 134.0, 130.3, 125.2, 120.5,

118.9, 117.9, 105.8 ppm.

4-(4-Methoxyphenoxy)benzonitrile (Table 2, entry 22).45 Prepared according to procedure A, using 4-

methoxyphenol (260 mg, 2.1 mmol), 4-fluorobenzonitrile (242 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g)


product (414 mg, 92% yield) as a white solid. mp: 101 °C (litt.: 100–101 °C). 1H NMR (400 MHz, CDCl3): δ

7.53 (m, 2H), 6.99 (m, 2H), 6.90 (m, 4H), 3.79 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 162.3, 156.9,

147.8, 134.0, 121.8, 119.0, 117.1, 115.2, 105.2, 55.4 ppm.

19

Ethyl 4-(4-methoxyphenoxy)benzoate (Table 2, entry 23).46 Prepared according to procedure A, using 4-

methoxyphenol (260 mg, 2.1 mmol), ethyl 4-fluorobenzoate (336 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54



(d, 3JHH = 8.6 Hz, 2H), 6.85 (m, 4H), 4.32 (q, 3JHH = 6.5 Hz, 2H), 3.90 (s, 3H), 1.42 (t, 3JHH = 6.5 Hz, 3H) ppm.

13C NMR (100 MHz, CDCl3): δ 166.5, 163.1, 156.6, 149.1, 132.0, 124.7, 122.2, 116.6, 115.1, 61.3, 56.4, 14.7

ppm.

Ethyl 4-phenoxybenzoate (Table 2, entry 24).46 Prepared according to procedure A, using phenol (197 mg, 2.1

mmol), ethyl 4-fluorobenzoate (336 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5 mL) at 110

°C. After 3.5 h, the crude product was recrystallized in methanol to afford the final product (436 mg, 90% yield)

as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.85–8.01 (m, 2H), 7.41-7.47 (m, 2H), 7.10–7.16 (m, 2H),

7.01–7.05 (m, 2H), 6.91–6.97 (m, 2H), 4.25 (q, 3JHH = 6.8 Hz, 2H), 1.41 (t, 3JHH = 6.8 Hz, 3H) ppm. 13C NMR

(100 MHz, CDCl3): δ 165.7, 162.1, 156.7, 131.5, 130.2, 124.7, 124.1, 60.8, 15.2 ppm.

4-Phenoxybenzaldehyde (Table 2, entry 25).51 Prepared according to procedure A, using phenol (197 mg, 2.1

mmol), 4-fluorobenzaldehyde (248 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5 mL) at 110 °C.

After 2.5 h, the crude product was recrystallized in methanol to afford the final product (337 mg, 85% yield) as

a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 9.92 (s, 1H), 7.68 (d, 3JHH = 8.6 Hz, 2H), 7.41 (d, 3JHH = 7.8

Hz, 2H), 7.21 (t, 3JHH = 8.2 Hz, 1H), 6.99 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ 191.2, 163.1, 156.2,

131.6, 131.0, 130.1, 125.2, 120.6, 117.7 ppm.

1-Nitro-4-phenoxybenzene (Table 2, entry 26).45 Prepared according to procedure A, using 4-phenol (197 mg,

2.1 mmol), 4-chloronitrobenzene (315 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5 mL) at 110


as a yellow solid. mp: 54 °C (litt.: 54–55 °C). 1H NMR (400 MHz, CDCl3): δ 7.02 (d, 3JHH = 9.1 Hz, 2H), 7.10

(d, 3JHH = 8.0 Hz, 2H), 7.25 (t, 3JHH = 7.2 Hz, 1H), 7.44 (t, 3JHH = 7.2 Hz, 2H), 8.20 (d, 3JHH = 9.1 Hz, 2H). 13C

NMR (100 MHz, CDCl3): δ 162.5, 153.8, 141.7, 129.5, 125.1, 124.6, 119.7, 116.2 ppm.

1-Nitro-4-phenoxybenzene (Table 2, entry 27).45 Prepared according to procedure A, using 4-phenol (197 mg,

2.1 mmol), 4-bromonitrobenzene (404 mg, 2.0 mmol), and 60% (w/w) CsF/CP (0.54 g) in DMSO (5 mL) at 110


20

as a yellow solid. mp: 54 °C (litt.: 54–55 °C). 1H NMR (400 MHz, CDCl3): δ 8.20 (d, 3JHH = 9.1 Hz, 2H), 7.45

(t, 3JHH = 7.2 Hz, 2H), 7.26 (t, 3JHH = 7.2 Hz, 1H), 7.10 (d, 3JHH = 8.0 Hz, 2H), 7.02 (d, 3JHH = 9.1 Hz, 2H). 13C

NMR (100 MHz, CDCl3): δ 162.5, 153.8, 141.7, 129.5, 126.1, 124.6, 119.7, 116.2 ppm.

Diphenylether (Table 5, entry 1).51 Prepared according to procedure B, using phenol (71 mg, 0.75 mmol),

iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at 120 °C. After 14 h, the

reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered. The resulting solution

was placed in a separatory funnel and washed twice with water. The organic layer was dried over anhydrous

sodium sulfate, filtered, and concentrated in vacuo. The crude products were purified by column

chromatography on silica gel eluting with ethyl acetate/hexane mixtures to afford the final product (77 mg, 91%

yield) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 7.37–7.26 (m, 4H), 7.02–7.10 (m, 2H), 6.94–7.03

(m, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ 157.1, 129.7, 123.1, 118.8 ppm.

2-Phenoxynaphthalene (Table 5, entry 2).51 Prepared according to procedure B, using 2-naphthol (108 mg,

0.75 mmol), iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at 120 °C.

After 18 h, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered. The

resulting solution was placed in a separatory funnel and washed twice with water. The organic layer was dried

over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude products were purified by column


yield) as a white solid. mp: 46 ºC (litt.: 45–47 °C). 1H NMR (300 MHz, CDCl3): δ 7.75–7.81(m, 2H), 7.62–7.69

(d, 3JHH = 7.7 Hz, 1H), 7.25–7.38 (m, 6H), 7.01–7.11 (m, 3H) ppm. 13C NMR (75 MHz, CDCl3): δ 157.0, 154.9,

134.2, 130.0, 129.7, 129.6, 127.6, 127.0, 126.4, 124.5, 123.3, 119.0, 119.8, 118.0, 113.9 ppm.

1-Chloro-4-phenoxybenzene (Table 5, entry 3).51 Prepared according to procedure B, using 4-chlorophenol

(118 mg, 0.75 mmol), iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at

120 °C. After 16 h, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered.

The resulting solution was placed in a separatory funnel and washed twice with water. The organic layer was

dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude products were purified by

column chromatography on silica gel eluting with ethyl acetate/hexane mixtures to afford the final product (82

mg, 80% yield) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 7.23–7.35 (m, 4H), 7.09–7.13 (m, 1H),

21

6.90–7.09 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ 156.8, 155.9, 129.8, 129.6, 128.1, 123.6, 120.0, 118.9

ppm.

1-Chloro-2-phenoxybenzene (Table 5, entry 4).51 Prepared according to procedure B, using 2-chlorophenol






mg, 72% yield) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 7.45 (dt, 3JHH = 7.9 Hz, 4JHH = 1.5 Hz, 1H),

7.27–7.35 (m, 2H), 7.18–7.22 (m, 1H), 7.04–7.11 (m, 2H), 6.92–7.01 (m, 3H). 13C NMR (100 MHz, CDCl3): δ

156.9, 152.4, 130.7, 129.7, 127.8, 125.8, 124.6, 123.3, 120.8, 117.8 ppm.

1-Methyl-4-phenoxybenzene (Table 5, entry 5).51 Prepared according to procedure B, using 4-methylphenol







7.03–7.08 (m, 1H), 6.93–6.99 (m, 2H), 6.85–6.91 (m, 2H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.8,

154.7, 132.8, 130.2, 129.6, 122.7, 119.1, 118.3, 20.6 ppm.

1-Methyl-2-phenoxybenzene (Table 5, entry 6).51 Prepared according to procedure B, using 2-methylphenol

(81. mg, 0.75 mmol), iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at





mg, 82% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.29–7.35 (m, 3H), 7.18–7.22 (m, 1H), 7.02–

22

7.11 (m, 2H), 6.88–6.97 (m, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.7, 154.3, 131.3, 129.8,

129.5, 126.9, 123.9, 122.1, 119.6, 117.1, 16.0 ppm.

4-Phenoxybenzonitrile (Table 5, entry 7).45 Prepared according to procedure B, using 4-cyanophenol (89 mg,

0.75 mmol), iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at 120 °C.

After 26 h, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered. The

resulting solution was placed in a separatory funnel and washed twice with water. The organic layer was dried

over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude products were purified by column


yield) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.52–7.59 (m, 2H), 7.34–7.41 (m, 2H), 7.18–7.23 (m,

1H), 7.03–7.09 (m, 2H), 6.96–7.02 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ 161.5, 154.8, 134.2, 130.3,

125.1, 120.4, 118.9, 117.9, 105.9 ppm.

1-Methoxy-2-phenoxybenzene (Table 5, entry 8).52 Prepared according to procedure B, using 2-

methoxyphenol (93 mg, 0.75 mmol), Iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in

DMSO (4 mL) at 120 °C. After 20 h, the reaction mixture was cooled to room temperature, diluted with ethyl

acetate, and filtered. The resulting solution was placed in a separatory funnel and washed twice with water. The

organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude products

were purified by column chromatography on silica gel eluting with ethyl acetate/hexane mixtures to afford the

final product (78 mg, 78% yield) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 7.38–7.42 (m, 2H), 7.12–

7.18 (m, 1H), 6.92–7.01 (m, 2H), 6.81–7.02 (m, 2H), 3.77 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 158,

151.6, 145.1, 129.6, 124.6, 122.6, 121.2, 121.1, 117.3, 112.9, 56.0 ppm.

1-Methoxy-4-phenoxybenzene (Table 5, entry 9).51 Prepared according to procedure B, using 4-

methoxyphenol (93 mg, 0.75 mmol), Iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in





final product (89 mg, 89% yield) as a colorless liquid. 1H NMR (400 MHz, CDCl3): δ 7.15–7.28 (m, 2H), 6.80–

23

7.10 (m, 7H), 3.77 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.4, 150.0, 155.7, 122.3, 129.7, 120.7, 117.5,

114.7, 55.4 ppm.

1-(tert-Butyl)-4-phenoxybenzene (Table 5, entry 10).51 Prepared according to procedure B, using 4-

tertbutylphenol (113 mg, 0.75 mmol), iodobenzene (102 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in





final product (102 mg, 90% yield) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.37–7.47 (m, 4H), 7.07–

7.14 (m, 2H), 7.03–7.10 (m, 3H), 1.35 (s, 9H) ppm. 13C NMR (75 MHz, CDCl3): δ 157.4, 154.5, 145.8, 129.5,

126.4, 122.7, 118.4, 118.3, 34.1, 31.3 ppm.

1-Methoxy-4-phenoxybenzene (Table 5, entry 11).51 Prepared according to procedure B, using phenol (71 mg,

0.75 mmol), 4-methoxyiodobenzene (117 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50 g) in DMSO (4 mL) at






3.77 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 158.4, 150.0, 155.7, 122.3, 129.7, 120.7, 117.5, 114.7, 55.4

ppm.

4,4'-Oxybis(methoxybenzene) (Table 5, entry 12).46 Prepared according to procedure B, using 4-

methoxyphenol (93 mg, 0.75 mmol), 4-methoxyiodobenzene (117 mg, 0.5 mmol), and 60% (w/w) CsF/CP (0.50

g) in DMSO (4 mL) at 120 °C. After 15 h, the reaction mixture was cooled to room temperature, diluted with

ethyl acetate, and filtered. The resulting solution was placed in a separatory funnel and washed twice with water.

The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude

products were purified by column chromatography on silica gel eluting with ethyl acetate/hexane mixtures to

afford the final product (98 mg, 85% yield). 1H NMR (400 MHz, CDCl3): δ 6.92 (d, 3JHH = 9.1 Hz, 4H), 6.85 (d,

3JHH = 9.1 Hz, 4H), 3.79 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ 155.3, 151.6, 119.5, 114.7, 55.7 ppm.

24

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Fig. 1 Activity of CsF/CP with various loadings of CsF: (♦) 4 mmol/g, (■) 7.5 mmol/g, (×) 9.5 mmol/g and (▲) 10.5 mmol/g.

Fig. 2 SEM (a) and TEM (b) images of nano-CuO particles.

(a) (b)

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