Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl 2 nanocatalyst

Abstract

A green synthesis of variously substituted biphenyl carboxylic acids was achieved through Suzuki–Miyaura cross-coupling of a bromobenzoic acid with an aryl boronic acid using a water-soluble fullerene-supported PdCl₂ nanocatalyst (C₆₀-TEGs/PdCl₂). Yields of more than 90% were obtained at room temperature in 4 h using 0.05 mol% catalyst and 2 equiv. K₂CO₃.

Keywords

Supported palladium nanocatalyst biphenyl carboxylic acid green synthesis Suzuki–Miyaura cross-coupling reaction

Introduction

Biphenyl carboxylic acid compounds play an important role in organic synthesis, in the pharmaceutical and petrochemical industries and in materials chemistry.^1–4 The pharmaceutical compounds Fenbufen and Flurbiprofen, which are excellent nonsteroidal anti-inflammatory drugs, are good examples. Biphenyl compounds are usually synthesized through a series of sometimes lengthy reactions. However, the defects of these traditional synthetic methods cannot be neglected, such as complicated steps, harsh reaction conditions, side reactions, difficult separation and purification, low yield and serious environmental pollution. This is obviously contrary to the theme of green environmental protection, energy saving and emission reduction, and is not in line with the concept of green chemistry. Fortunately, the construction of C–C bonds by a Suzuki–Miyaura cross-coupling reaction can be achieved in only one step and the unnecessary derivatization steps can be reduced.^5–8 Recently we synthesized a fullerene-supported PdCl₂ nanocatalyst (Figure 1) and successfully used it to synthesize biphenyl compounds via a Suzuki–Miyaura cross-coupling of aryl bromides and chlorides with aryl boronic acids.⁹ We now report its successful use in synthesizing biphenyl carboxylic compounds via a Suzuki–Miyaura cross-coupling of aryl bromides containing a carboxyl group with aryl boronic acids.

Figure 1.

Water-soluble fullerene supported PdCl₂ nanocatalyst [C₆₀-TEG_S/PdCl₂].

Results and discussion

Optimization of the coupling reaction conditions

The Suzuki–Miyaura cross-coupling reaction between 4-bromobenzoic acid (1; R¹ = CO₂H) and phenyl boronic acid (2; R² = H) catalyzed by C₆₀-TEGS/PdCl₂ (Scheme 1) was selected as a model reaction in order to optimize the reaction conditions (amount of catalyst, base used and reaction time) and the results are shown in Table 1. When the amount of catalyst was increased from 0.01 to 0.05 mol%, the yield was significantly enhanced, but the yield did not increase after increasing the amount of catalyst to 0.15 mol% (Table 1, entries 1–5). Thus 0.05 mol% of catalyst is the optimal dose for this reaction. On prolonging the reaction time from 1 to 4 h (Table 1, entries 3 and 6–8), the yield increased markedly. In 6 h (Table 1, entry 9), the yield remained at 97%. On varying the base (Table 1, entries 2 and 10–14), we found that Cs₂CO₃ was superior, leading to a high yield of 98% within 4 h. The yield with K₂CO₃ was similar but other bases such as Na₂CO₃, NaHCO₃, KF and K₃PO₄ gave lower yields. However, considering that Cs₂CO₃ is more expensive than K₂CO₃, K₂CO₃ was chosen as the best base. In summary, 0.05 mol% C₆₀-TEGs/PdCl₂, 4 h of reaction time and 2.0 mmol of K₂CO₃ as base were the optimal conditions.

Scheme 1.

Biphenyl carboxylic acids via Suzuki – Miyaura cross-coupling catalyzed by water-soluble fullerene-supported PdCl2 nanocatalyst.

Table 1.

Optimization of the conditions (amount of catalyst, base used and reaction time) for the preparation of biphenyl-4-carboxylic acid (3a; R¹ = 4-CO₂H, R² = H) by treatment of 4-bromobenzoic acid (1; R¹ = 4-CO₂H) with phenyl boronic acid (2; R² = H) in the presence of a water-soluble fullerene-supported PdCl₂ nanocatalyst (C₆₀-TEGs/PdCl₂) (Scheme 1)^a.

Entry	C₆₀-TEGs/PdCl₂ (mol%)	Base	Time (h)	Yield (%)^b
1	0.15	K₂CO₃	4	98
2	0.10	K₂CO₃	4	98
3	0.05	K₂CO₃	4	97
4	0.025	K₂CO₃	4	89
5	0.01	K₂CO₃	4	50
6	0.05	K₂CO₃	1	41
7	0.05	K₂CO₃	2	73
8	0.05	K₂CO₃	3	91
9	0.05	K₂CO₃	6	97
10	0.05	Na₂CO₃	4	91
11	0.05	NaHCO₃	4	86
12	0.05	KF	4	77
13	0.05	K₃PO₄	4	93
14	0.05	Cs₂CO₃	4	98

Reaction conditions: a mixture of 4-bromobenzoic acid (1; R¹ = 4-CO₂H) (1.0 mmol), phenyl boronic acid (2; R² = H) (1.2 mmol) and a base (2.0 mmol) in H₂O (5.0 mL) was stirred for various times at room temperature in the presence of various amounts of C₆₀-TEGs/PdCl₂.

Isolated yields.

Substrate expansion

To investigate further the scope and generality of this methodology, the cross-couplings of various aryl bromides containing a carboxyl or a phenol group with various aryl boronic acids were carried out under the optimized conditions and the results are shown in Table 2. When 4-bromobenzoic acid was coupled with an aryl boronic acid with electron-donating or electron-withdrawing groups at the para-position, the corresponding products were obtained in excellent yields (Table 2, entries 1–3). However, the yield of 3,5-difluoroaryl boronic acid coupling with 4-bromobenzoic acid decreased to 76% (Table 2, entry 4^a), which demonstrated that reactivity of the coupling reaction decreased when the aryl boronic acid contained strongly electron-withdrawing groups. When we increased the amount of the catalyst to 0.10% mol, the yield recovered to 93% (Table 2, entry 4^c). When 3-bromobenzoic acid, 4-bromophenylacetic acid and 5-bromosalicylic acid replaced 4-bromobenzoic acid, it was found that the coupling yields with the various aryl boronic acids were high and followed the above rules (Table 2, entries 5–19). There were no clear differences in yield among 3-bromobenzoic acid, 4-bromobenzoic acid, 4-bromophenylacetic acid and 5-bromosalicylic acid. However, under the same conditions, the coupling reaction of 2,4-difluorophenyl boronic acid with its more hindered ortho-position led to a significantly lower yield of 73% (Table 2, entry 20^c). In order to obtain a higher yield, it needed a longer reaction time (6 h) and a greater amount of catalyst (0.25% mol). It is probable that a steric effect is being observed. Because they are more atom economical and cheaper than aryl bromides, aryl chlorides were also used as substrates in the coupling reaction. 4-Chlorobenzoic acid was coupled with phenyl boronic acid with 0.50 mol% of water-soluble fullerene supported PdCl₂ nanocatalyst to give a 75% yield at a higher temperature in 12 h (Table 2, entry 21), whereas for the more challenging reaction of 4-chlorobenzoic and 4-fluoroaryl boronic acid a slightly lower yield was obtained (Table 2, entry 22). Thus, aryl chlorides containing a carboxyl group are much more difficult to couple with aryl boronic acids requiring stronger conditions of heating and a prolonged reaction time.

Table 2.

Yields of a series of variously substituted biphenyls (3a–u; R¹, R² = various) prepared by the reaction of bromobenzoic acids (1; R¹ = various) with an aryl boronic acid (2; R² = various) in the presence of a water-soluble fullerene-supported PdCl₂ nanocatalyst (C₆₀-TEGs/PdCl₂) (Scheme 1)^a.

Entry	(1, R¹)	(2, R²)	Product	Yield (%)^b
1	4-CO₂H	4-CH₃	3b	97
2	4-CO₂H	4-F	3c	97
3	4-CO₂H	4-OCH₃	3d	98
4	4-CO₂H	3,5-Difluoro	3e	76^a 93^c
5	3-CO₂H	H	3f	96
6	3-CO₂H	4-CH₃	3g	96
7	3-CO₂H	4-F	3h	96
8	3-CO₂H	4-OCH₃	3i	97
9	3-CO₂H	3,5-Difluoro	3j	91^c
10	4-CH₂CO₂H	H	3k	97
11	4-CH₂CO₂H	4-CH₃	3l	96
12	4-CH₂CO₂H	4-F	3m	96
13	4-CH₂CO₂H	4-OCH₃	3n	97
14	4-CH₂CO₂H	3,5-Difluoro	3o	92^c
15	3-CO₂H-4-OH	H	3p	96
16	3-CO₂H-4-OH	4-CH₃	3q	95
17	3-CO₂H-4-OH	4-F	3r	95
18	3-CO₂H-4-OH	4-OCH₃	3s	96
19	3-CO₂H-4-OH	3,5-Difluoro	3t	91^c
20	3-CO₂H-4-OH	2,4-Difluoro	3u	73^c 90^d
21	4-Chlorobenzoic acid	H	3a	75^e
22	4-Chlorobenzoic acid	F	3c	72^e

Reaction conditions: a mixture of a bromobenzoic acid (1; R¹ = various) (1.0 mmol), an aryl boronic acid (2; R² = various) (1.2 mmol) and K₂CO₃ (2.0 mmol) in H₂O (5.0 mL) was stirred for 4 h at room temperature in the presence of 0.05 mol% C₆₀-TEGs/PdCl₂.

Isolated yields.

0.10 mol% catalyst was used

0.25 mol% catalyst was used and reaction time was 6 h.

A mixture of 4-chlorobenzoic acid (1.0 mmol) and aryl boronic acid (1.5 mmol) (2; R² = H or F) was used for 12 h at 80°C in the presence of 0.50 mol% catalyst.

Experimental

C₆₀ fullerene, tetraethylene glycol (TEG), palladium chloride, phenyl boronic acid, aryl halides and lithium hydroxide were purchased from Energy Chemical and were used without further purification. Other commercially available reagents were purchased from Aladdin and were used without further purification. ¹H NMR spectra (400 MHz) were obtained on a Bruker ARX 400 NMR spectrometer in CDCl₃. Chemical shifts (δ) are given in ppm and coupling constants (J) are given in hertz (Hz). The XT4A melting point measuring instrument (Beijing Keyi electro-optic instrument factory, China) was used to determine melting points.

Suzuki-Miyaura cross-coupling reaction catalyzed by C₆₀-TEGs/PdCl₂

A 50 mL flask was charged with an aryl halide (1.0 mmol), an aryl boronic acid (1.2 mmol), K₂CO₃ (2.0 mmol), nanocatalyst (0.05 mol% Pd) and deionized water (5 mL). The reaction was stirred at room temperature for 4 h. The progress of the reaction was monitored by thin-layer chromatography. After the reaction was completed, distilled water (25 mL) was added to the mixture and dilute 2 mol/L HCl was added dropwise to pH 3.0-4.0 with stirring, and the mixture was heated to 100 °C for 10 min. The white solid that had formed was filtered off and washed with hot water. After drying, it was dissolved in ether (5 mL) and was rapidly separated using a silica gel column. Elution with ether left behind small amounts of impurities and traces of palladium black to give a crude product. The ether solution was evaporated to 3–5 mL and recrystallized to obtain a pure product. All the products 3a–u are known compounds and were characterized by comparing their melting points and ¹H NMR spectra with those prepared recently by using a water-soluble glycine-based Pd catalyst, PdCl₂(NH₂CH₂CO₂H)₂.¹⁰ The melting points and ¹H NMR data of 3a–u are listed in the supplemental material.

Supplemental Material

JCR1805731v2_ESI – Supplemental material for Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst

Supplemental material, JCR1805731v2_ESI for Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst by Wanyun Liu, Xiuming Zhou, Ping Huo, Jingbo Li and Guangquan Mei in Journal of Chemical Research

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the National Natural Science Foundation of China (No. 21764016 and No. 21664014), the Natural Science Foundation of Jiangxi Province (No. 20161BAB215197) and the Foundation of Jiangxi Provincial Education Department (No. GJJ151031 and GJJ170901).

Supplemental material

The supplemental material for this article is available online.

References

Parlow

Burney

Case

et al . J Med Chem 2010; 53: 2010.

Davies

Less

Lickiss

et al . Dalton Trans 2007; 24: 2528.

Bright

Dalton

Elder

et al . Org Biomol Chem 2013; 11: 1135.

Andrews

Ferrero

Junk

et al . Dalton Trans 2010; 39: 2861.

Hong

X-M

Collard

et al . Org Lett 2000; 2: 2385.

Almond-Thynne

Blakemore

Pryde

et al . Chem Sci 2017; 1: 40.

Han

D-X

Zhang

Z-G

Bao

Z-B

et al . Front Chem Sci Eng 2018; 12: 24.

Liu

Jin

. Green Chem 2012; 14: 592.

J-B

Huo

Zheng

J-W

et al . RSC Adv 2018; 8: 24231.

10.

Liu

S-W

M-Y

Xiao

D-A

et al . Org Biomol Chem 2014; 12: 4511.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.10 MB