Synthesis of aryl 5-(2-chlorophenyl)-2-furoates under phase transfer catalysis

Article abstract of DOI:10.1081/SCC-120013716

The steric hindered esters, aryl 5-(2-chlorophenyl)-2-furoates (3a-o), are synthesized via the reaction of 5-(2-chlorophenyl)-2-furoic acid (1) with thionyl chloride and phenols under liquid-liquid phase transfer catalysis in excellent yield.

Full text of DOI:10.1081/SCC-120013716

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SYNTHESIS OF ARYL 5-(2-CHLOROPHENYL)-2-FUROATES
UNDER PHASE TRANSFER CATALYSIS
Zheng Li a & Xicun Wang a
a College of Chemistry and Chemical Engineering , Northwest Normal University , Lanzhou,
Gansu, 730070, P.R. China
Published online: 16 Aug 2006.
To cite this article: Zheng Li & Xicun Wang (2002) SYNTHESIS OF ARYL 5-(2-CHLOROPHENYL)-2-FUROATES UNDER PHASE
TRANSFER CATALYSIS, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 32:20, 3081-3086, DOI: 10.1081/SCC-120013716
To link to this article: http://dx.doi.org/10.1081/SCC-120013716
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3081–3086, 2002
SYNTHESIS OF ARYL
5-(2-CHLOROPHENYL)-2-FUROATES
UNDER PHASE TRANSFER CATALYSIS
*
Zheng Li and Xicun Wang
College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou,
Gansu, 730070, P.R. China
ABSTRACT
The steric hindered esters, aryl 5-(2-chlorophenyl)-2-furoates
(3a–o), are synthesized via the reaction of 5-(2-chlorophenyl)-
2-furoic acid (1) with thionyl chloride and phenols under
liquid–liquid phase transfer catalysis in excellent yield.
5-Aryl-2-furoic acid derivatives have attracted much attention due to
their diverse biological activities, such as antibacterial,[1,2] anesthetic[3] anti-
convulsive[4] and plant-growth regulating[5,6] activity. However, the species
of aryl 5-aryl-2-furoates are very scarce[2] because of the steric hindrance.
This promotes us to investigate a convenient and efficient method to synthe-
size these compounds so that the properties and activities can be further
investigated.
*Corresponding author. E-mail: lizheng@nwnu.edu.cn
3081
DOI: 10.1081/SCC-120013716
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3082
LI AND WANG
Reaction of 5-(2-chlorophenyl)-2-furoic acid (1) with thionyl chloride
catalyzed by benzyl triethyl ammonium chloride (BTEAC) gives 5-(2-chloro-
phenyl)-2-furoyl chloride (2) in 95% yield. Compound 2 on further treatment
with phenols catalyzed by polyethylene glycol-400 (PEG-400) affords aryl
5-(2-chlorophenyl)-2-furoates (3a–o) in excellent yield (Sch. 1).
It is worthy to mention that this is a very simple, facile and one pot
synthetic method for the steric hindered furoates under mild condition.
In order to confirm the optimal synthetic condition, different phase
transfer catalysts, including 18-crown-6, (C4H9)4NI, (C4H9)4NBr, BTEAC,
(C16H33)N(CH3)3Br, PEG-400, PEG-600 and PEG-1000, are tested for the
selected compound 3a. The results are shown in Table 1.
Scheme 1.
Table 1. The Influence of Phase Transfer Catalysts
on the Yield of 3a
Catalyst
Solvent
Yield
18-Crown-6
(C4H9)4NI
(C4H9)4NBr
BTEAC
(C16H33)N(CH3)3Br
PEG-1000
PEG-600
PEG-400
PEG-400
PEG-400
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
C6H6
70
68
74
69
70
75
80
86
85
75
0
CH2Cl2

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ARYL 5-(2-CHLOROPHENYL)-2-FUROATES
3083
From Table 1, we can see that all of the catalysts used in the reactions
are able to catalyze the reaction to give the title compounds in good to
excellent yield. Among of them, PEG-400 is the best under the studied
condition. However, if no catalyst used, the product cannot be obtained
at all in the same condition. In addition, the solvents can also influence
the yield of the reaction.
The characterization of compounds 3a–o is based on their IR (KBr),
1H NMR MS and elemental analyses. The IR spectra exhibit a characteristic
strong absorption at 1732–1748 cmꢀ1 attributable to the carbonyl of 3a–o.
All elemental analyses and MS of 3a–o are good agreement with the
structure prepared.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on an Alpha Centauri
1
FT-IR spectrophotometer and H NMR spectra on a FT-80A instrument
using CDCl3 as solvent and Me4Si as internal standard. Elemental
analyses were performed on a Vario El Elemental Analysis instrument.
Mass spectra were recorded on a QP-1000A GC-MS using the impact
mode (70 eV). Melting points were observed in an open capillary
tube and uncorrected. 5-(2-Chlorophenyl)-2-furoic acid (1) was prepared
according to literature procedure.[5] Phenols, thionyl chloride,
18-crown-6, (C4H9)4NI, (C4H9)4NBr, (C16H33)N(CH3)3Br, PEG-400,
PEG-600 and PEG-1000 were commercially available and used as
received.
General Procedure for the Preparation of Compounds 3a–o
The mixture of 0.49 g (2.2 mmol) of 5-(2-chlorophenyl)-2-furoic
acid (1), 5 mL of SOCl2 and 0.05 g (0.22 mmol) of BTEAC in 10 mL
of CHCl3 was refluxed for 2 h. Then the excess of SOCl2 and CHCl3
was removed by evaporation. The residue was extracted with petroleum
ether. After removal of the solvent, a solution of 0.08 g (2.00 mmol)
of NaOH in 8 mL of H2O, 2.00 mmol of phenol, 0.024 g (0.06 mmol) of
PEG-400 and 15 mL CH2Cl2 were added. The resulting mixture was
stirred for 1 h at room temperature. Then the organic layer was separated
and the water layer was extracted with CH2Cl2 (2 ꢁ 5 mL). The resulting
organic solution was dried with anhydrous Na2SO4. After the solvent
was removed by evaporation, the residue was recrystallized from C2H5OH

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LI AND WANG
to give 3a–o. The physical and spectral data of compounds 3a–o are
reported below.
Phenyl 5-(2-chlorophenyl)-2-furoate (3a): White solid. Yield: 86%.
M.p.: 82–83ꢂC. H NMR (CDCl3) ꢀ 7.15–8.13 (m, 11H, Ar-H and Fu-H).
1
IR (KBr, ꢁ, cmꢀ1): 1732 (C¼O), 1301, 1222, 1109 (C-O-C). MS: m/z,
298 (Mþ). Anal. Calcd. for C17H11O3Cl: C, 68.35; H, 3.71. Found: C,
68.12; H, 3.68.
2,4-Dinitrophenyl 5-(2-chlorophenyl)-2-furoate (3b): White solid. Yield:
85%. M.p.: 152–153ꢂC. H NMR (CDCl3) ꢀ 7.21–8.87 (m, 9H, Ar-H and
1
Fu-H). IR (KBr, ꢁ, cmꢀ1): 1746 (C¼O), 1307, 1239, 1104 (C-O-C). MS: m/z,
388 (Mþ). Anal. Calcd. for C17H9N2O7Cl: C, 52.53; H, 2.33; N, 7.21.
Found: C, 52.29; H, 2.24; N, 7.16.
2,6-Dinitrophenyl 5-(2-chlorophenyl)-2-furoate (3c): White solid. Yield:
82%. M.p.: 122–123ꢂC. H NMR (CDCl3) ꢀ 7.19–8.55 (m, 9H, Ar-H and
1
Fu-H). IR (KBr, ꢁ, cmꢀ1): 1748 (C¼O), 1306, 1245, 1108 (C-O-C). MS: m/z,
388 (Mþ). Anal. Calcd. for C17H9N2O7Cl: C, 52.53; H, 2.33; N, 7.21.
Found: C, 52.41; H, 2.28; N, 7.13.
2-Nitrophenyl 5-(2-chlorophenyl)-2-furoate (3d): White solid. Yield:
90%. M.p.: 132–133ꢂC. H NMR (CDCl3) ꢀ 7.12–8.20 (m, 10H, Ar-H and
1
Fu-H). IR (KBr, ꢁ, cmꢀ1): 1745 (C¼O), 1307, 1227, 1105 (C-O-C). MS: m/z,
343 (Mþ). Anal. Calcd. for C17H10NO5Cl: C, 59.40; H, 2.93; N, 4.08.
Found: C, 59.26; H, 2.86; N, 3.89.
3-Nitrophenyl 5-(2-chlorophenyl)-2-furoate (3e): White solid. Yield:
81%. M.p.: 142–143ꢂC. 1H NMR (CDCl3) ꢀ 7.14–8.22 (m, 10H, Ar-H
and Fu-H). IR (KBr, ꢁ, cmꢀ1): 1743 (C¼O), 1303, 1221, 1101 (C-O-C).
MS: m/z, 343 (Mþ). Anal. Calcd. for C17H10NO5Cl: C, 59.40; H, 2.93; N,
4.08. Found: C, 59.29; H, 2.90; N, 3.99.
4-Nitrophenyl 5-(2-chlorophenyl)-2-furoate (3f): White solid. Yield:
84%. M.p.: 146–147ꢂC. H NMR (CDCl3) ꢀ 7.12–8.19 (m, 10H, Ar-H and
1
Fu-H). IR (KBr, ꢁ, cmꢀ1): 1748 (C¼O), 1305, 1224, 1104 (C-O-C). MS: m/z,
343 (Mþ). Anal. Calcd. for C17H10NO5Cl: C, 59.40; H, 2.93; N, 4.08.
Found: C, 59.56; H, 2.89; N, 3.98.
2,4-Dichlorophenyl 5-(2-chlorophenyl)-2-furoate (3g): White solid.
Yield: 87%. M.p.: 121–122ꢂC. 1H NMR (CDCl3) ꢀ 7.13–8.08 (m, 9H,
Ar–H and Fu-H). IR (KBr, ꢁ, cmꢀ1): 1744 (C¼O), 1304, 1223, 1120
(C-O-C). MS: m/z, 367 (Mþ). Anal. Calcd. for C17H9O3Cl3: C, 55.54; H,
2.47. Found: C, 55.34; H, 2.41.
4-Chlorophenyl 5-(2-chlorophenyl)-2-furoate (3h): White solid. Yield:
84%. M.p.: 110–111ꢂC. H NMR (CDCl3) ꢀ 7.18–8.15 (m, 10H, Ar-H and
1
Fu-H). IR (KBr, ꢁ, cmꢀ1): 1740 (C¼O), 1303, 1221, 1097 (C-O-C). MS: m/z,
333 (Mþ). Anal. Calcd. for C17H10O3Cl2: C, 61.29; H, 3.03. Found: C,
61.03; H, 2.96.

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ARYL 5-(2-CHLOROPHENYL)-2-FUROATES
3085
1-Naphthyl 5-(2-chlorophenyl)-2-furoate (3i): White solid. Yield: 83%.
M.p.: 78–79ꢂC. H NMR (CDCl3) ꢀ 7.19–8.12 (m, 13H, Ar-H and Fu-H).
1
IR (KBr, ꢁ, cmꢀ1): 1735 (C¼O), 1304, 1215, 1110 (C-O-C). MS: m/z,
348 (Mþ). Anal. Calcd. for C21H13O3Cl: C, 72.32; H, 3.76. Found: C,
72.08; H, 3.68.
2-Naphthyl 5-(2-chlorophenyl)-2-furoate (3j): White solid. Yield: 87%.
M.p.: 126–127ꢂC. 1H NMR (CDCl3) ꢀ 7.21–8.14 (m, 13H, Ar-H and Fu-H).
IR (KBr, ꢁ, cmꢀ1): 1733 (C¼O), 1305, 1206, 1105 (C-O-C). MS: m/z,
348 (Mþ). Anal. Calcd. for C21H13O3Cl: C, 72.32; H, 3.76. Found: C,
72.12; H, 3.70.
4-Methoxylphenyl 5-(2-chlorophenyl)-2-furoate (3k): White solid. Yield:
93%. M.p.: 122–123ꢂC. H NMR (CDCl3) ꢀ 7.08–8.07 (m, 10H, Ar-H and
1
Fu-H), 3.75 (s, 3H, CH3). IR (KBr, ꢁ, cmꢀ1): 1742 (C¼O), 1305, 1214, 1109
(C-O-C). MS: m/z, 328 (Mþ). Anal. Calcd. for C18H13O4Cl: C, 65.76; H,
3.99. Found: C, 65.59; H, 4.08.
2-Methylphenyl 5-(2-chlorophenyl)-2-furoate (3l): White solid. Yield:
92%. M.p.: 80–81ꢂC. H NMR (CDCl3) ꢀ 7.20–8.12 (m, 10H, Ar-H and
1
Fu-H), 2.27 (s, 3H, CH3). IR (KBr, ꢁ, cmꢀ1): 1742 (C¼O), 1306, 1223,
1116 (C-O-C). MS: m/z, 312 (Mþ). Anal. Calcd. for C18H13O3Cl: C,
69.13; H, 4.19. Found: C, 68.92; H, 4.11.
3-Methylphenyl 5-(2-chlorophenyl)-2-furoate (3m): White solid. Yield:
84%. M.p.: 104–105ꢂC. H NMR (CDCl3) ꢀ 7.23–8.14 (m, 10H, Ar-H and
1
Fu-H), 2.31 (s, 3H, CH3). IR (KBr, ꢁ, cmꢀ1): 1739 (C¼O), 1305, 1227, 1121
(C-O-C). MS: m/z, 312 (Mþ). Anal. Calcd. for C18H13O3Cl: C, 69.13; H,
4.19. Found: C, 68.85; H, 4.14.
2-Methylphenyl 5-(2-chlorophenyl)-2-furoate (3n): White solid. Yield:
82%. M.p.: 102–103ꢂC. H NMR (CDCl3) ꢀ 7.19–8.13 (m, 10H, Ar-H and
1
Fu-H), 2.29 (s, 3H, CH3). IR (KBr, ꢁ, cmꢀ1): 1741 (C¼O), 1304, 1217, 1112
(C-O-C). MS: m/z, 312 (Mþ). Anal. Calcd. for C18H13O3Cl: C, 69.13; H,
4.19. Found: C, 69.28; H, 4.23.
5,7-Dichloro-8-quinolyl 5-(2-chlorophenyl)-2-furoate (3o): White solid.
Yield: 85%. M.p.: 154–155ꢂC. 1H NMR (CDCl3) ꢀ 7.14–8.17 (m, 10H,
Ar–H, Py-H and Fu-H). IR (KBr, ꢁ, cmꢀ1): 1743 (C¼O), 1297, 1226,
1118 (C-O-C). MS: m/z, 418 (Mþ). Anal. Calcd. for C20H10NO3Cl3: C,
57.38; H, 2.41; N, 3.35. Found: C, 57.13; H, 2.49; N, 3.21.
ACKNOWLEDGMENT
The authors thank the Scientific and Technological Innovation
Engineering of Northwest Normal University and Natural Science
Foundation of Gansu Province for the financial support of this work.

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Received in Japan April 16, 2001