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Synthesis 2015; 47(11): 1661-1668
DOI: 10.1055/s-0034-1380463
paper
© Georg Thieme Verlag Stuttgart · New York

Palladium Nanoparticles Catalyzed Synthesis of Benzofurans by a Domino Approach

Pavan Kumar Mandali
Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu-600 036, India   Email: dillip@iitm.ac.in
,
Dillip Kumar Chand*
Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu-600 036, India   Email: dillip@iitm.ac.in
› Author Affiliations
Further Information

Publication History

Received: 23 January 2015

Accepted after revision: 02 March 2015

Publication Date:
08 April 2015 (online)

 
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Palladium Nanoparticles Catalyzed Synthesis of Benzofurans by a Domino ApproachSynthesis 2015; 47(11): e4-e4
DOI: 10.1055/s-0034-1378729

Abstract

Palladium nanoparticles (PdNPs) were used as a catalyst for the one-pot synthesis of a variety of benzofurans by Sonogashira cross-coupling reactions under ambient conditions. The catalyst could be recycled without significant loss in its activity.


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Key words

palladium - nanostructures - catalysis - domino reaction - cross-coupling

Palladium compounds are well used as catalysts in a variety of organic transformations reactions.[1] Among palladium compounds, the use of palladium nanoparticles (PdNPs) in catalysis has been a recent trend.[2] Typical palladium nanoparticles are stabilized by a suitable capping agent, e.g. dendrimers, polymers, ionic liquids, and designed organic ligands.[3] However, ligand-free palladium nanoparticles (LF-PdNPs) are also known to catalyze organic reactions, though very limited in number.[4] Ligand-free palladium nanoparticles are probably stabilized by the coordinating solvents that are used for their preparation. The C–C coupling reactions, such as the Suzuki, Heck, and Sonogashira reactions, have been well studied using a variety of ligand-stabilized palladium nanoparticles.[5] However, there are fewer reports on the use of ligand-free palladium nanoparticles for such coupling reactions. Although palladium nanoparticles are used to catalyze Sonogashira reactions, their use in the synthesis of benzofurans via Sonogashira reactions is not well explored.[5b] To the best of our knowledge there are only two reports on the use of palladium nanoparticles as catalysts for the synthesis of benzofurans.[6]

Benzofurans exhibit a broad range of biological activity against asthma, ulcers, type 2 diabetes, and some other disorders. The unique benzofuran structure is also found in the core of many natural products.[7] For these reasons the development of efficient strategies for the synthesis of benzofurans is important.[8] The domino approach towards the synthesis of benzofurans by Sonogashira cross-coupling between 2-halophenols and arylacetylenes is attractive due to the fact that this protocol provides better yields of the desired compounds and also tolerates various functional groups present in the substrates.[9] Domino reactions provide efficient routes in synthetic organic transformations to achieve complex molecules in one pot; this approach is efficient because the separation of unstable intermediates is unnecessary.[10]

In our previous communications, we discussed the catalytic activity of thoroughly characterized ligand-free palladium nanoparticles towards Suzuki[4d] and Sonogashira cross-coupling reactions.[4a] [11] In the present work, we would like to discuss the role of ligand-free palladium nanoparticles in the synthesis of a variety of benzofurans under mild reaction conditions without using an inert atmosphere. Triphenylphosphine is used as a co-ligand for the synthesis of aryl-substituted benzofurans, hence the palladium nanoparticles used for catalysis are not in the strictest sense ligand-free. Symmetrical and unsymmetrical dibenzofurans could be prepared by controlling the ratio of the reactants. Along with benzofuran 1a, a rare type[12] of substituted benzofuran 2, a new, fluorescent active compound is isolated as a minor product. Such structures were found in medicinally important compounds reported recently.[12a]

Condensation of 2-iodophenol with phenylacetylene was carried out under various reaction conditions to optimize the synthesis of 2-phenylbenzofuran (1a) (Table [1]). The results suggest that the reaction temperature and catalytic loading play major roles in terms of product formation as well as isolated yields. A slight increase in the catalyst loading, i.e. from 2 to 2.5 mol%, gave a huge improvement in the yield and reaction time (entry 2 vs. 5). Similarly, addition of triphenylphosphine increased the yield of 1a (entry 3 vs. 5). A new benzofuran derivative, 2-phenyl-3-(phenylethynyl)benzofuran (2), was isolated as a minor product under the reaction conditions employed.

Table 1 Optimization of the Reaction Conditions for the Synthesis of 2-Phenylbenzofuran (1a)

Entry

PdNPs/Ph3P (mol%)

Temp (°C)

Time (h)

Yielda (%)

1a

2

1

2/10

30

24

31

~5

2

2/20

60

10

40

~5

3

2.5/–

60

10

41

~5

4

2.5/20

30

 5

72

~5

5

2.5/20

60

 5

79

~5

6b

2.5/20

60

20

25

–

a Isolated yield,

b Et3N was employed instead of K2CO3.

A series of benzofurans 1a–v were prepared by domino reaction of 2-iodophenol or methyl 4-hydroxy-3-iodobenzoate with a variety of terminal aryl- or alkylacetylenes under the optimized reaction condition [PdNPs (2.5 mol%), Ph3P (20 mol%), 60 °C] (Scheme [1,]Tables 2 and 3).

Zoom Image
Scheme 1 Palladium nanoparticles catalyzed synthesis of benzofurans by coupling of 2-iodophenols and terminal aryl- or alkylacetylenes

Arylacetylenes bearing a methyl group at ortho-, meta-, or para-position are coupled smoothly with 2-iodophenol to give the corresponding benzofurans 1b–d in good yields (entries 2–4); the use of the 2-tolyl group also exemplifies steric hindrance in the acetylene substrate. Both electron-deficient and electron-rich arylacetylenes gave the corresponding products in good yields. A heterocyclic acetylene 3-ethynylpyridine gave corresponding benzofuran 1h in 81% yield (entry 8). The coupling reactions between 2-iodophenols and arylacetylenes bearing electron-withdrawing group like trifluoromethyl, cyano, fluoro, or bromo, proceeded smoothly and the products 1j–l,o were isolated in high yields (entries 10–12 and 15). Notably, benzofurans 1o,p could be prepared in high yields even in cases where electron-withdrawing groups are present in both 2-iodophenol and arylacetylene moieties (entries 15 and 16). The isolated benzofuran 1a was subjected to ICP-OES analysis which showed that no palladium is detected in the sample. This experiment indicates that the palladium content, if any, is below the detection limit.

Table 2 Synthesis of Aryl-Substituted Benzofurans

Entry

R

Ar

Time (h)

Product

Yielda (%)

 1b

H

Ph

5

1a

79

 2

H

2-MeC6H4

6

1b

81

 3

H

3-MeC6H4

3

1c

70

 4

H

4-MeC6H4

2

1d

72

 5

H

4-t-BuC6H4

8

1e

78

 6

H

3-H2NC6H4

2.5

1f

86

 7

H

4-H2NC6H4

2

1g

81

 8

H

3-pyridyl

2.5

1h

81

 9c

H

3-HC≡CC6H4

5

1i

68

10

H

3-F3CC6H4

4

1j

75

11

H

4-NCC6H4

3

1k

81

12

H

2,4-F2C6H3

4

1l

79

13

H

4-BrC6H4

3

1m

87

14

CO2Me

Ph

4

1n

86

15

CO2Me

4-NCC6H4

3

1o

87

16

CO2Me

4-BrC6H4

3.5

1p

88

a Isolated yields after column chromatography.

b 2-Phenyl-3-(phenylethynyl)benzofuran (2) was isolated in 5% yield.

c 1,3-Di(benzofuran-2-yl)benzene (3) was isolated in 11% yield.

Coupling 2-iodophenol with 1,3-diethynylbenzene gave a benzofuran derivative 1i bearing one unreacted acetylene moiety in 68% yield together with the symmetrical 1,3-dibenzofuran 3 in 11% yield (Table [2], entry 9, and Scheme [2]). Our efforts to increase the yield of the symmetrical 1,3-dibenzofuran 3 by reacting 1,3-diethynylbenzene with three and five equivalents of 2-iodophenol gave the targeted compound 3 in 41 and 52% yields, respectively.

Zoom Image
Scheme 2 Influence of the stoichiometry of the reactants in Sonogashira coupling reactions on the yield of 1,3-dibenzofuran 3

Several of the benzofurans 1f,g,i,k,m,o,p (Table [2], entries 6, 7, 9, 11, 13, 15 and 16) contain functional groups that are suitable for further derivatization. For instance, the derivatizable benzofurans 1i and 1m are subjected to Sonogashira­ and Suzuki coupling reactions, respectively, using the same palladium nanoparticles and a protocol that we had previously developed (see Schemes 4 and 5).[4a] [d]

Thus, 2-(3-ethynylphenyl)benzofuran (1i) was coupled with 2-iodophenols to synthesize symmetrical 3 and unsymmetrical 4 dibenzofurans in excellent yields (Scheme [3]).

Zoom Image
Scheme 3 Coupling reactions between 2-(3-ethynylphenyl)benzofuran (1i) and iodophenols

The benzofuran 1i bearing an unreacted acetylene was further coupled with 4-iodoanisole and sterically hindered substrate 2-iodo-1,3-dimethylbenzene in the presence of palladium nanoparticles (2 mol%) at room temperature for one hour to afford the corresponding coupling products 5 and 6 (Scheme [4]).

Zoom Image
Scheme 4 Derivatization of 2-(3-ethynylphenyl)benzofuran (1i) by Sonogashira coupling reactions

The coupling reaction between 2-iodophenol and 1-bromo-4-ethynylbenzene afforded 2-(4-bromophenyl)benzofuran (1m) (Table [2], entry 13) in good yield and this was further derivatized using 3-tolylboronic acid as a coupling partner for the Suzuki coupling reaction using a protocol that we have previously developed (Scheme [5]).[4d]

Zoom Image
Scheme 5 Suzuki coupling of 2-(4-bromophenyl)benzofuran (1m) and 3-tolylboronic acid

Alkylacetylenes, such as hex-1-yne, dec-1-yne and hex-5-yn-1-ol, were coupled with two different 2-iodophenols to give corresponding benzofurans 1q–v in good yields (Table [3]) without the addition of triphenylphosphine and within short reaction times (Table [3]).

The recycling of palladium nanoparticles was examined for the preparation of benzofuran 1a. It was observed that the catalyst could be reused for at least four catalytic cycles (Figure [1]). No significant loss in the yield of the major product was observed between cycles. The slight loss in the activity of the catalyst can be ascribed to the agglomeration of the palladium nanoparticles.[13] This was established by analyzing the TEM of the catalyst before the 1st cycle and after the 4th cycle (Figure [2]). The sizes of the palladium nanoparticles before catalysis fall in the range of 4.5–8 nm whereas after the 4th cycle the calculated sizes were in the range of 12–18 nm.

Table 3 Synthesis of Alkyl-Substituted Benzofurans

Entry

R1

R2

Time (h)

Product

Yield (%)a

1

H

Bu

1

1q

91

2

H

(CH2)7Me

1

1r

92

3

H

(CH2)4OH

1.5

1s

87

4

CO2Me

Bu

1

1t

91

5

CO2Me

(CH2)7Me

1

1u

91

6

CO2Me

(CH2)4OH

2

1v

86

a Isolated yields.

Zoom Image
Figure 1 Representation of the recyclability of palladium nanoparticles as catalyst in the synthesis of benzofuran 1a
Zoom Image
Figure 2 TEM images of palladium nanoparticles (a) before catalysis and (b) after the 4th cycle of the preparation of benzofuran 1a

As discussed, a seldom found type of benzofuran derivative 2 (Table [1]) was isolated as a minor product during the synthesis of 1a.[12] Since, compound 2 is fluorescent active and no photophysical studies have been reported in literature for such compounds, a preliminary investigation was performed (Figure [3]). The absorption spectrum of compound 2 in chloroform shows two distinct absorption maxima at 306 and 320 nm. An emission maximum is observed at 355 nm when compound 2 is excited at either 306 or 320 nm.

Zoom Image
Figure 3 UV-vis (left) and fluorescence (right) spectra of compound 2 (CHCl3)

In conclusion, we have demonstrated that palladium nanoparticles catalyzed the one-pot synthesis of benzofurans. A variety of aryl- and alkylbenzofurans were synthesized in good yields. The catalyst could be recycled without significant loss in its activity for at up to four catalytic cycles for the synthesis of benzofuran 1a. A preliminary photophysical study of a new compound is presented.

All reagents were purchased from Sigma-Aldrich and purified solvents were used to perform the reactions. The coupling reactions were monitored by TLC using silica gel as a stationary phase. 1H and 13C NMR were recorded at r.t. with a Bruker Avance-400 and 500 MHz FT NMR spectrometers. The mass spectra of the samples were obtained from a Micromass Q-TOF mass spectrometer by electrospray ionization method (ESI) and GC-MS recorded on Jeol GCMATE II GC-MS mass spectrometer. High-resolution TEM images were obtained from Jeol 3010 with a UHR pole piece operates at an accelerating voltage 300 kV. UV-Visible absorption spectrum was recorded on Jasco V-630 spectrophotometer and fluorescence spectra were recorded on a Jasco FP-6300 spectrofluorometer. ICP-OES measurements were carried out on a Perkin Elmer Optima 5300 DV.

Analytical data of all the new and known compounds are provided and the spectra are collected in the Supporting Information. The new benzofurans are 1f,l,o,p,s,u,v, 2–7. Analytical data of the previously reported compounds are in good agreement with the literature data.


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Ligand-free Palladium Nanoparticles (LF-PdNPs); General Procedure

The LF-PdNPs were prepared by using a protocol established from our group and also characterized.[4a] [d] Pd(OAc)2 (0.0056 g, 0.025 mmol) was dissolved in MeOH–MeCN (1:1, 12.5 mL) to give a yellow-colored solution that was 2 mM in metal. The yellow solution was stirred at r.t. for about 3 h whereupon brownish-black color developed due to reduction of Pd(II) to Pd(0). The size of the thus-prepared PdNPs was in the range 4.5–8 nm by TEM analysis.


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2-Phenylbenzofuran (1a); Typical Procedure

A freshly prepared solution of PdNPs (12.5 mL) was taken up in a 25-mL round-bottomed flask. To this solution K2CO3 (0.276 g, 2 mmol) and Ph3P (0.052 g, 0.2 mmol) were added followed by 2-iodophenol (0.22 g, 1 mmol) and phenylacetylene (0.122 g, 1.2 mmol). Then, the mixture was stirred at 60 °C under aerobic conditions. The reaction was monitored by TLC until complete consumption of phenylacetylene. When the reaction was complete, the solvents were evaporated and the residue was purified by column chromatography (hexane–EtOAc). Yields for all compounds are calculated after column chromatography. The catalyst could be recycled. The size of the PdNPs after four catalytic cycles was found in the range of 12–18 nm by TEM analysis indicating some agglomeration.

The reactions of 2-iodophenol or methyl 4-hydroxy-3-iodobenzoate with arylacetylenes were carried out as given in the typical procedure. However, reactions using alkylacetylenes did not require the use of Ph3P.


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Symmetrical and Unsymmetrical Dibenzofurans 3 and 4; General Procedure (Scheme 3)

A freshly prepared solution of PdNPs (6.2 mL) was taken up in a 25-mL round-bottomed flask. To this solution, K2CO3 (0.138 g, 1 mmol) and Ph3P (0.026 g, 0.1 mmol) were added followed by 2-iodophenol (0.110 g, 0.5 mmol) or methyl 4-hydroxy-3-iodobenzoate (0.139 g, 0.5 mmol) and 2-(3-ethynylphenyl)benzofuran (0.109 g, 0.5 mmol). Then, the mixture was stirred at 60 °C under aerobic conditions. The reaction was monitored by TLC until complete consumption of the terminal acetylene compound.


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2-[3-(Arylethynyl)phenyl]benzofurans 5 and 6 by Sonogashira Coupling Reactions; General Procedure

The PdNPs were prepared by using a protocol established from our group.[4a] A freshly prepared solution of PdNPs (5 mL) was taken up in a 25-mL round-bottomed flask. To this solution, K2CO3 (0.138 g, 1 mmol was added followed by 4-iodoanisole (0.117 g, 0.5 mmol) or 2-iodo-1,3-dimethylbenzene (0.116 g, 0.5 mmol) and 2-(3-ethynylphenyl)benzofuran (0.109 g, 0.5 mmol). Then, the mixture was stirred at r.t. in an open atmosphere. The reaction was monitored by TLC until complete consumption of the starting materials.


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2-(3′-Methylbiphenyl-4-yl)benzofuran (7)

The PdNPs were prepared by using a protocol established from our group.[4d] A freshly prepared solution of PdNPs (5 mL) was taken up in a 25-mL round-bottomed flask. To this solution, K2CO3 (0.138 g, 1 mmol) was added followed by 2-(4-bromophenyl)benzofuran (0.136 g, 0.5 mmol) and 3-tolylboronic acid (0.081 g, 0.6 mmol). Then, the mixture was stirred at r.t. in open atmosphere. The reaction was monitored by TLC until complete consumption of the starting material.


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Recyclability of the Catalyst for Synthesis of Benzofuran 1a

We have investigated the recyclability of the catalytic system by choosing 2-iodophenol and phenylacetylene as model substrates. After one run, the mixture was centrifuged and the supernatant was decanted. The residue was washed with hexane and then MeOH (2 ×) to extract the organic products. Then it was dried under reduced pressure and redispersed in MeOH–MeCN (12.5 mL) to generate the catalyst. The required amount of K2CO3 was added followed by the organic substrates to carry out the next catalytic cycle. The regenerated catalyst system was found to be reusable without any significant loss of the catalytic activity for at least 4 cycles.


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2-Phenylbenzofuran (1a)[8c]

White solid; yield: 153.3 mg (79%); mp 118 °C.

1H NMR (500 MHz, CDCl3): δ = 7.87–7.85 (d, J = 10 Hz, 2 H), 7.58–7.57 (s, 1 H), 7.53–7.51 (d, J = 10 Hz, 1 H), 7.45–7.42 (t, J = 8 Hz, 2 H), 7.35–7.32 (t, 1 H), 7.29–7.26 (t, J = 8 Hz, 1 H), 7.23–7.20 (m, 1 H), 7.01 (s, 1 H).

13C NMR (125 MHz, CDCl3): δ = 156.06, 155.03, 132.65, 130.63, 128.92, 128.69, 125.07, 124.40, 123.07, 121.04, 111.32, 101.44.


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2-(2-Tolyl)benzofuran (1b)[14a]

Colorless oil; yield: 169 mg (81%).

1H NMR (500 MHz, CDCl3): δ = 7.86–7.83 (m, 1 H), 7.62–7.60 (m, 1 H), 7.54–7.51 (m, 1 H), 7.32–7.30 (m, 4 H), 7.26–7.22 (m, 1 H), 6.899–6.896 (d, J = 1.2 Hz, 1 H), 2.58 (s, 3 H).

13C NMR (125 MHz, CDCl3): δ = 155.82, 154.54, 135.99, 133.07, 131.41, 128.66, 128.32, 126.24, 125.80, 124.37, 122.93, 121.05, 111.24, 105.24, 22.06.


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2-(3-Tolyl)benzofuran (1c)[14a]

Colorless solid; yield: 145.6 mg (70%); mp 76 °C.

1H NMR (500 MHz, CDCl3): δ = 7.67 (s, 1 H), 7.65–7.63 (d, J = 10 Hz, 1 H), 7.56–7.49 (m, 2 H), 7.50–7.48 (d, J = 10 Hz, 1 H), 7.32–7.29 (t, J = 6 Hz, 1 H), 7.27–7.23 (dt, 1 H), 7.21–7.19 (m, 1 H), 7.15–7.13 (d, J = 10 Hz, 1 H), 6.97 (s, 1 H), 2.40 (s, 3 H).

13C NMR (125 MHz, CDCl3): δ = 156.2, 154.9, 138.6, 130.5, 129.5, 129.3, 128.8, 125.7, 124.3, 123.0, 122.3, 121.0, 111.3, 102.3, 21.6.

HRMS: m/z [M + H]+ calcd for C15H13O: 209.0966; found: 209.0960.


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2-(4-Tolyl)benzofuran (1d)[8c]

White solid; yield: 149.8 mg (72%); mp 127 °C.

1H NMR (400 MHz, CDCl3): δ = 7.76–7.74 (d, J = 8 Hz, 2 H), 7.57–7.55 (d, J = 8 Hz, 1 H), 7.51–7.49 (d, J = 8 Hz, 1 H), 7.26–7.21 (m, 4 H), 6.96 (s, 1 H), 2.39 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 156.3, 154.92, 138.74, 132.54, 129.63, 127.9, 125.04, 124.13, 122.99, 120.88, 111.23, 100.7, 21.52.

HRMS: m/z [M + H]+ calcd for C15H13O: 209.0966; found: 209.0957.


#

2-(4-tert-Butylphenyl)benzofuran (1e)[8c]

White solid; yield: 195 mg (78%); mp 128–130 °C.

1H NMR (500 MHz, CDCl3): δ = 7.81–7.79 (d, J = 10 Hz, 2 H), 7.58–7.50 (m, 2 H), 7.48–7.46 (d, J = 10 Hz, 2 H), 7.29–7.19 (m, 2 H), 6.98–6.97 (d, J = 5 Hz, 1 H), 1.34 (s, 9 H).

13C NMR (125 MHz, CDCl3): δ = 156.31, 154.97, 151.95, 129.50, 127.88, 125.87, 124.89, 124.12, 122.97, 120.89, 111.26, 100.81, 34.91, 31.39.

HRMS: m/z [M + H]+ calcd for C18H19O: 251.3495; found: 251.3495.


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2-(3-Aminophenyl)benzofuran (1f)

Brown solid; yield: 179 mg (86%); mp 124–126 °C.

1H NMR (400 MHz, CDCl3): δ = 7.58–7.56 (d, J = 8 Hz, 1 H), 7.51–7.49 (d, J = 8 Hz, 1 H), 7.29–7.20 (m, 5 H), 6.97 (s, 1 H), 6.69–6.67 (m, 1 H), 3.08 (s, 2 H).

13C NMR (100 MHz, CDCl3): δ = 156.28, 154.96, 146.89, 131.59, 129.89, 129.39, 124.30, 123.01, 120.99, 115.70, 111.48, 111.26, 101.43.

HRMS: m/z [M + H]+ calcd for C14H12NO: 210.0919; found: 210.0929.


#

2-(4-Aminophenyl)benzofuran (1g)[14b]

Brown solid; yield: 169 mg (81%); mp 149–151 °C.

1H NMR (400 MHz, CDCl3): δ = 7.68–7.66 (d, J = 8 Hz, 2 H), 7.53–7.46 (m, 2 H), 7.23–7.18 (m, 2 H), 6.81 (s, 1 H), 6.75–6.73 (d, J = 8 Hz, 2 H), 3.83 (s, 2 H).

13C NMR (100 MHz, CDCl3): δ = 156.83, 154.66, 147.08, 129.80, 126.53, 123.49, 122.84, 121.21, 120.46, 115.19, 110.99, 98.71.


#

2-(3-Pyridyl)benzofuran (1h)[14c]

White solid; yield: 157 mg (81%); mp 82 °C.

1H NMR (400 MHz, CDCl3): δ = 9.12 (s, 1 H), 8.59–8.57 (d, J = 8 Hz, 1 H), 8.14–8.12 (d, J = 8 Hz, 1 H), 7.63–7.61 (d, J = 8 Hz, 1 H), 7.56–7.54 (d, J = 8 Hz, 1 H), 7.40–7.37 (dd, 1 H), 7.35–7.31 (dt, 1 H), 7.27–7.24 (t, 1 H), 7.13 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 155.24, 153.05, 149.41, 146.56, 132.04, 128.90, 126.79, 125.10, 123.77, 123.42, 121.36, 111.47, 102.90.

HRMS: m/z [M + H]+ calcd for C13H10NO: 196.0762; found: 196.0756.


#

2-(3-Ethynylphenyl)benzofuran (1i)[14d]

White solid; yield: 148 mg (68%); mp 80–82 °C.

1H NMR (500 MHz, CDCl3): δ = 8.01–8.00 (t, 1 H), 7.86–7.83 (m, 1 H), 7.61–7.58 (m, 1 H), 7.54–7.51 (m, 1 H), 7.48–7.45 (m, 1 H), 7.43–7.39 (m, 1 H), 7.32–7.28 (m, 1 H), 7.26–7.22 (m, 1 H), 7.052–7.050 (d, 1 H), 3.13 (s, 1 H).

13C NMR (125 MHz, CDCl3): δ = 155.09, 154.93, 132.12, 130.88, 129.16, 128.99, 128.66, 125.32, 124.76, 123.22, 122.90, 121.22, 111.39, 102.16, 83.34, 77.82.


#

2-[3-(Trifluoromethyl)phenyl]benzofuran (1j)[14e]

White solid; yield: 196.5 mg (75%); mp 65 °C.

1H NMR (400 MHz, CDCl3): δ = 8.10 (s, 1 H), 8.01–7.99 (d, J = 8 Hz, 1 H), 7.60–7.52 (m, 4 H), 7.33–7.30 (dt, 1 H), 7.26–7.23 (m, 1 H), 7.09 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 155.2, 154.4, 131.4, 129.5, 129.0, 128.0, 125.1 (t, J= 16.5, 14 Hz), 123.4, 121.8, 121.7, 121.4, 111.5, 102.8.

HRMS: m/z [M + K]+ calcd for C15H9F3OK: 301.0243; found: 301.0247.


#

4-(Benzofuran-2-yl)benzonitrile (1k)[14f]

White solid; yield: 195.2 mg (81%); mp 142–144 °C.

1H NMR (500 MHz, CDCl3): δ = 7.96–7.94 (d, J = 10 Hz, 2 H), 7.74–7.72 (d, J = 10 Hz, 2 H), 7.64–7.62 (dd, J = 7.5 Hz, 1 H), 7.55–7.53 (dd, J = 8 Hz, 1 H), 7.37–7.34 (m, 1 H), 7.29–7.27 (m, 1 H), 7.18 (d, 1 H).

13C NMR (125 MHz, CDCl3): δ = 155.41, 153.71, 134.63, 132.78, 128.81, 125.71, 125.28, 123.59, 121.65, 118.89, 111.68, 111.58, 104.49.

HRMS: m/z [M + Na]+ calcd for C15H9NONa: 242.0582; found: 242.0588.


#

2-(2,4-Difluorophenyl)benzofuran (1l)

White solid; yield: 181.7 mg (79%); mp 131–133 °C.

1H NMR (500 MHz, CDCl3): δ = 8.05–7.99 (m, 1 H), 7.62–7.60 (m, 1 H), 7.53–7.51 (m, 1 H), 7.33–7.29 (m, 1 H), 7.27–7.23 (m, 1 H), 7.18–7.17 (m, 1 H), 7.03–6.92 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = 163.74 (d, J = 12 Hz), 161.74 (d, J = 12 Hz), 160.89 (d, J = 12 Hz), 158.86 (d, J = 12 Hz), 154.26, 149.16, 129.36, 128.21 (dd, J = 10 Hz), 124.88, 123.24, 121.46, 112.05 (dd, J = 21.25 Hz), 106.12 (d, J = 12.5 Hz), 104 (t, J = 25 Hz).

19F NMR (470 MHz, CDCl3): δ = –108.39 (d, J = 8.93 Hz), –109.32 (d, J = 8.93 Hz).

GC-MS: m/z = 232 [M + 2 H]+.


#

2-(4-Bromophenyl)benzofuran (1m)[8c]

White solid; yield: 236 mg (87%); mp 156–158 °C.

1H NMR (400 MHz, CDCl3): δ = 7.74–7.72 (d, J = 10 Hz, 2 H), 7.59–7.56 (m, 3 H), 7.52–7.50 (d, J = 10 Hz, 1 H), 7.32–7.27 (m, 1 H), 7.23–7.21 (m, 1 H), 7.03 (d, 1 H).

HRMS: m/z [M + Na]+ calcd for C14H9BrONa: 294.9734; found: 294.9733.


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Methyl 2-Phenylbenzofuran-5-carboxylate (1n)[14g]

White solid; yield: 216.7 mg (86%); mp 154–156 °C.

1H NMR (500 MHz, CDCl3): δ = 8.32 (dd, J = 1 Hz, 1 H), 8.02–8.00 (dd, J = 2.5 Hz, 1 H), 7.88–7.86 (m, 2 H), 7.55–7.53 (m, 1 H), 7.48–7.44 (m, 2 H), 7.40–7.36 (m, 1 H), 7.07 (d, J = 1.5 Hz, 1 H), 3.95 (s, 3 H).

13C NMR (125 MHz, CDCl3): δ = 167.45, 157.56, 157.53, 130.02, 129.39, 129.18, 129.02, 126.20, 125.47, 125.21, 123.45, 111.15, 101.66, 52.26.

HRMS: m/z [M + H]+ calcd for C16H13O3: 253.0865; found: 253.0867.


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Methyl 2-(4-Cyanophenyl)benzofuran-5-carboxylate (1o)

White solid; yield: 240 mg (87%); mp 152–154 °C.

1H NMR (500 MHz, CDCl3): δ = 8.29 (d, J = 1.5 Hz, 1 H), 8.02–7.99 (dd, J = 7.5 Hz, 1 H), 7.90–7.88 (d, J = 10 Hz, 2 H), 7.69–7.67 (d, J = 10 Hz, 2 H), 7.51–7.49 (d, J = 10 Hz, 1 H), 7.16 (d, J = 1.5 Hz, 1 H), 3.89 (s, 3 H).

13C NMR (125 MHz, CDCl3): δ = 167.15, 157.82, 155.15, 134.01, 132.87, 128.83, 127.33, 126.03, 125.47, 124.08, 118.11, 112.26, 111.46, 104.69, 52.39.

HRMS: m/z [M + H]+ calcd for C17H12NO3: 278.0817; found: 278.0825.


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Methyl 2-(4-Bromophenyl)benzofuran-5-carboxylate (1p)

White solid; yield: 290 mg (88%); mp 180–182 °C.

1H NMR (500 MHz, CDCl3): δ = 8.33–8.32 (d, J = 5 Hz, 1 H), 8.04–8.02 (dd, J = 10 Hz, 1 H), 7.75–7.73 (d, J = 10 Hz, 2 H), 7.60–7.58 (d, J = 10 Hz, 2 H), 7.54–7.52 (d, J = 10 Hz, 1 H), 7.08 (s, 1 H), 3.95 (s, 3 H).

13C NMR (125 MHz, CDCl3): δ = 167.34, 157.55, 156.41, 132.25, 129.22, 128.96, 126.65, 126.51, 125.67, 123.57, 123.25, 111.20, 102.22, 52.30.

GC-MS: m/z = 329 [M – H]+, 331 [M – H + 2]+.


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2-Butylbenzofuran (1q)[7c]

Yellow oil; yield: 158 mg (91%).

1H NMR (500 MHz, CDCl3): δ = 7.48–7.47 (m, 1 H), 7.43–7.41 (m, 1 H), 7.23–7.16 (m, 2 H), 6.383–6.381 (d, 1 H), 2.80–2.76 (t, 2 H), 1.78–1.71 (quint, 2 H), 1.49–1.40 (quint, 2 H), 0.99–0.95 (t, 3 H).

13C NMR (125 MHz, CDCl3): δ = 159.88, 154.75, 129.17, 123.13, 122.47, 120.26, 110.82, 101.87, 29.93, 28.28, 22.42, 13.94.

HRMS: m/z [M + H]+ calcd for C12H15O: 175.1123; found: 175.1128.


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2-Octylbenzofuran (1r)[9e]

Yellow oil; yield: 211 mg (92%).

1H NMR (500 MHz, CDCl3): δ = 7.48–7.46 (d, J = 10 Hz, 1 H), 7.42–7.40 (d, J = 10 Hz, 1 H), 7.22–7.16 (m, 2 H), 6.37 (s, 1 H), 2.78–2.75 (t, J = 7.5 Hz, 2 H), 1.77–1.71 (quint, J = 7.5 Hz, 2 H), 1.32–1.27 (m, 10 H), 0.90–0.87 (t, J = 7.5 Hz, 3 H).

13C NMR (125 MHz, CDCl3): δ = 159.93, 154.74, 129.17, 123.12, 122.47, 120.27, 110.82, 101.86, 31.99, 29.47, 29.35, 28.60, 27.84, 22.80, 14.24.


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4-(Benzofuran-2-yl)butan-1-ol (1s)

Colorless oil; yield: 165 mg (87%).

1H NMR (500 MHz, CDCl3): δ = 7.48–7.47 (m, 1 H), 7.41–7.39 (m, 1 H), 7.22–7.16 (m, 2 H), 6.39 (d, J = 1 Hz, 1 H), 3.71–3.68 (t, J = 6.5 Hz, 2 H), 2.83–2.80 (t, J = 7.5 Hz, 2 H), 1.87–1.81 (m, 2 H), 1.69–1.67 (t, J = 10 Hz, 2 H), 1.32 (s, 1 H).

13C NMR (125 MHz, CDCl3): δ = 159.25, 154.77, 129.05, 123.28, 122.56, 120.35, 110.86, 102.20, 68.67, 62.73, 32.27, 28.31, 24.11.

HRMS: m/z [M + H]+ calcd for C12H15O2: 191.1072; found: 191.1073.


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Methyl 2-Butylbenzofuran-5-carboxylate (1t)[15]

Colorless oil; yield: 211 mg (91%).

1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 1.2 Hz, 1 H), 7.94–7.92 (dd, J = 8 Hz, 1 H), 7.42–7.40 (m, 1 H), 6.43 (d, J = 0.8 Hz, 1 H), 3.92 (s, 3 H), 2.80–2.76 (t, 2 H), 1.77–1.70 (quint, 2 H), 1.47–1.38 (quint, 2 H), 0.98–0.94 (t, J = 7.2 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 167.66, 161.48, 157.44, 129.19, 125.15, 124.87, 122.73, 110.65, 102.34, 52.16, 29.77, 28.27, 22.42, 13.92.

HRMS: m/z [M + H]+ calcd for C14H17O3: 233.1178; found: 233.1167.


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Methyl 2-Octylbenzofuran-5-carboxylate (1u)

Colorless oil; yield: 262 mg (91%).

1H NMR (400 MHz, CDCl3): δ = 8.20 (d, J = 1.6 Hz, 1 H), 7.94–7.92 (dd, J = 8.2 Hz, 1 H), 7.42–7.40 (d, J = 10 Hz, 1 H), 6.42 (d, J = 0.8 Hz, 1 H), 3.92 (s, 3 H), 2.78–2.74 (t, J = 7.5 Hz, 2 H), 1.78–1.70 (quint, J = 7.5 Hz, 2 H), 1.30–1.25 (m, 10 H), 0.89–0.86 (t, J = 6.8 Hz, 3 H).

13C NMR (100 MHz, CDCl3): δ = 167.63, 161.50, 157.43, 129.19, 124.88, 122.72, 110.63, 102.32, 52.12, 31.97, 29.42, 29.32, 28.57, 27.67, 22.78, 14.20.

HRMS: m/z [M + H]+ calcd for C18H25O3: 289.1804; found: 289.1797.


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Methyl 2-(4-Hydroxybutyl)benzofuran-5-carboxylate (1v)

Yellow oil; yield: 278 mg (86%).

1H NMR (400 MHz, CDCl3): δ = 8.19 (d, J = 1.6 Hz, 1 H), 7.94–7.91 (dd, J = 8.8 Hz, 1 H), 7.41–7.39 (d, J = 8.8 Hz, 1 H), 6.44 (d, J = 0.8 Hz, 1 H), 3.91 (s, 3 H), 3.71–3.68 (t, J = 6.5 Hz, 2 H), 2.83–2.80 (t, J = 7.5 Hz, 2 H), 1.86–1.82 (m, 2 H), 1.69–1.67 (t, J = 10 Hz, 2 H), 1.32 (s, 1 H).

13C NMR (100 MHz, CDCl3): δ = 167.63, 160.87, 157.43, 129.07, 125.24, 122.77, 110.65, 102.60, 62.56, 52.14, 32.20, 28.28, 27.97, 23.98.

HRMS: m/z [M + H]+ calcd for C14H17O4: 249.1127; found: 249.1120.


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2-Phenyl-3-(phenylethynyl)benzofuran (2)

Yellow solid; yield: 14.7 mg (~5%); mp 150–152 °C.

1H NMR (400 MHz, CDCl3): δ = 8.37–8.35 (d, J = 8.0 Hz, 2 H), 7.78–7.76 (m, 1 H), 7.66–7.63 (m, 2 H), 7.55–7.50 (m, 3 H), 7.44–7.40 (m, 4 H), 7.37–7.33 (m, 2 H).

13C NMR (100 MHz, CDCl3): δ = 156.45, 153.68, 131.67, 130.33, 130.07, 129.31, 128.81, 128.62, 128.58, 126.19, 125.50, 123.53, 120.51, 111.34, 99.37, 96.61, 81.33.

HRMS: m/z [M + H]+ calcd for C22H15O: 295.1123; found: 295.1131.


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1,3-Di(benzofuran-2-yl)benzene (3)

Yellow solid; yield: 137 mg (89%); mp 162–164 °C.

1H NMR (500 MHz, CDCl3): δ = 8.38–8.37 (t, J = 2 Hz, 1 H), 7.86–7.84 (dd, J = 6 Hz, 2 H), 7.63–7.61 (m, 2 H), 7.59–7.57 (m, 2 H), 7.55–7.52 (t, J = 8 Hz, 1 H), 7.34–7.30 (m, 2 H), 7.28–7.24 (m, 2 H), 7.152–7.150 (d, J = 1 Hz, 2 H).

13C NMR (125 MHz, CDCl3): δ = 155.25, 155.12, 131.24, 129.48, 129.28, 125.06, 124.68, 123.20, 121.41, 121.19, 111.41, 102.11.

HRMS: m/z [M + K]+ calcd for C22H14O2K: 349.0631; found: 349.0624.


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Methyl 2-[3-(Benzofuran-2-yl)phenyl]benzofuran-5-carboxylate (4)

Yellow solid; yield: 167 mg (91%); mp 161–163 °C.

1H NMR (400 MHz, CDCl3): δ = 8.36–8.34 (m, 2 H), 8.05–8.03 (dd, J = 6.8 Hz, 1 H), 7.87–7.83 (m, 2 H), 7.63–7.52 (m, 4 H), 7.34–7.31 (m, 1 H), 7.27–7.24 (m, 1 H), 7.18 (s, 1 H), 7.15 (s, 1 H), 3.96 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 167.41, 157.62, 156.98, 155.31, 155.12, 131.34, 130.64, 129.52, 129.30, 129.23, 126.44, 125.60, 125.50, 125.15, 124.76, 123.59, 121.50, 121.22, 111.42, 111.24, 102.32, 102.25, 52.30.

HRMS: m/z [M + H]+ calcd for C24H17O4: 369.1127; found: 369.1134.


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2-{3-[(4-Methoxyphenyl)ethynyl]phenyl}benzofuran (5)

White solid; yield: 155 mg (96%); mp 138–140 °C.

1H NMR (400 MHz, CDCl3): δ = 8.03–8.02 (t, J = 2 Hz, 1 H), 7.82–7.80 (m, 1 H), 7.61–7.59 (m, 1 H), 7.55–7.48 (m, 5 H), 7.43–7.39 (t, J = 6 Hz, 1 H), 7.32–7.22 (m, 2 H), 7.058–7.056 (d, J = 0.8 Hz, 1 H), 6.90–6.88 (d, J = 8 Hz, 2 H), 3.84 (s, 3 H).

13C NMR (100 MHz, CDCl3,): δ = 159.92, 155.26, 155.09, 133.29, 131.49, 130.83, 129.24, 128.97, 127.99, 124.65, 124.48, 124.41, 123.17, 121.17, 115.32, 114.21, 111.36, 102.01, 90.09, 87.82, 55.47.

GC-MS: m/z = 324 [M]+.

Anal. Calcd for C23H16O2·0.5H2O: C, 82.86; H, 5.14. Found: C, 82.50; H, 4.60.


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2-{3-[(2,6-Dimethylphenyl)ethynyl]phenyl}benzofuran (6)

White solid; yield: 148 mg (92%); mp 98–100 °C.

1H NMR (500 MHz, CDCl3): δ = 8.03–8.02 (t, J = 1.5 Hz, 1 H), 7.84–7.82 (dt, J = 8 Hz, 1 H), 7.61–7.59 (m, 1 H), 7.56–7.53 (m, 2 H), 7.46–7.43 (t, J = 8 Hz, 1 H), 7.32–7.29 (m, 1 H), 7.26–7.23 (m, 1 H), 7.17–7.14 (m, 1 H), 7.10–7.08 (m, 3 H), 2.56 (s, 6 H).

13C NMR (125 MHz, CDCl3): δ = 155.21, 155.11, 140.56, 131.54, 130.91, 129.23, 129.02, 128.11, 127.77, 126.89, 124.69, 124.67, 124.62, 123.20, 122.91, 121.19, 111.40, 102.11, 97.47, 87.80, 21.34.

HRMS: m/z [M + H]+ calcd for C24H19O: 323.1358; found: 323.4157.


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2-(3′-Methylbiphenyl-4-yl)benzofuran (7)

White solid; yield: 128 mg (91%); mp 162–164 °C.

1H NMR (400 MHz, CDCl3): δ = 7.94–7.92 (d, J = 8 Hz, 2 H), 7.69–7.67 (d, J = 8 Hz, 2 H), 7.60–7.58 (m, 1 H), 7.54–7.52 (m, 1 H), 7.46–7.44 (m, 2 H), 7.37–7.34 (t, J = 8 Hz, 1 H), 7.31–7.27 (td, J = 8 Hz, 1 H), 7.25–7.21 (m, 1 H), 7.20–7.18 (d, J = 8 Hz, 1 H), 7.06 (d, 1 H), 2.44 (s, 3 H).

13C NMR (100 MHz, CDCl3): δ = 155.90, 155.10, 141.54, 140.58, 138.63, 129.45, 128.93, 128.49, 127.92, 127.62, 125.44, 124.42, 124.26, 123.11, 121.03, 111.32, 101.51, 21.70.

HRMS: m/z [M + H]+ calcd for C21H17O: 285.1279; found: 285.1290.


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Acknowledgment

D.K.C. thanks CSIR, India for financial support. P.K.M. thanks IIT Madras­ for a fellowship.

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0034-1380463.
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Zoom Image
Scheme 1 Palladium nanoparticles catalyzed synthesis of benzofurans by coupling of 2-iodophenols and terminal aryl- or alkylacetylenes
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Scheme 2 Influence of the stoichiometry of the reactants in Sonogashira coupling reactions on the yield of 1,3-dibenzofuran 3
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Scheme 3 Coupling reactions between 2-(3-ethynylphenyl)benzofuran (1i) and iodophenols
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Scheme 4 Derivatization of 2-(3-ethynylphenyl)benzofuran (1i) by Sonogashira coupling reactions
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Scheme 5 Suzuki coupling of 2-(4-bromophenyl)benzofuran (1m) and 3-tolylboronic acid
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Figure 1 Representation of the recyclability of palladium nanoparticles as catalyst in the synthesis of benzofuran 1a
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Figure 2 TEM images of palladium nanoparticles (a) before catalysis and (b) after the 4th cycle of the preparation of benzofuran 1a
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Figure 3 UV-vis (left) and fluorescence (right) spectra of compound 2 (CHCl3)