One pot synthesis of N-aryl-5-aryl-2-furoyl amides via reaction of 5-aryl-2-furoic acid with arylamines

Article abstract of DOI:10.1081/SCC-120014043

The N-aryl-5-aryl-2-furoyl amides (3a-r) are synthesized by one pot method via reaction of 5-aryl-2-furoic acids (1) with arylamines, using phenylsulfonyl chloride as reagent, under solid-liquid phase transfer catalysis in excellent yield.

Full text of DOI:10.1081/SCC-120014043

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ONE POT SYNTHESIS OF N-ARYL-5-ARYL-2-FUROYL
AMIDES VIA REACTION OF 5-ARYL-2-FUROIC ACID WITH
ARYLAMINES
Zheng Li a & Xicun Wang b
a College of Chemistry and Chemical Engineering , Northwest Normal University , Lanzhou,
Gansu, 730070, P.R. China
b 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) ONE POT SYNTHESIS OF N-ARYL-5-ARYL-2-FUROYL AMIDES VIA REACTION OF
5-ARYL-2-FUROIC ACID WITH ARYLAMINES, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:21, 3357-3362, DOI: 10.1081/SCC-120014043
To link to this article: http://dx.doi.org/10.1081/SCC-120014043
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 21, pp. 3357–3362, 2002
ONE POT SYNTHESIS OF N-ARYL-5-
ARYL-2-FUROYL AMIDES VIA REACTION
OF 5-ARYL-2-FUROIC ACID
WITH ARYLAMINES
*
Zheng Li and Xicun Wang
College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou,
Gansu, 730070, P.R. China
ABSTRACT
The N-aryl-5-aryl-2-furoyl amides (3a–r) are synthesized by
one pot method via reaction of 5-aryl-2-furoic acids (1) with
arylamines, using phenylsulfonyl chloride as reagent, under
solid–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] anesthetic,[2]
anticonvulsive[3] and plant-growth regulating[4,5] activity. However, the
species of N-aryl-5-aryl-2-furoyl amides are very scarce because in the
synthetic reactions of which, the large furan and aryl rings of 5-aryl-2-
furoic acid and large aryl ring of arylamine have strong steric hindrance,
*Corresponding author. E-mail: lizheng@nwnu.edu.cn
3357
DOI: 10.1081/SCC-120014043
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3358
LI AND WANG
which makes the nucleophilic substitution between two reactants very
difficult. This promotes us to develop a convenient and efficient new
method to synthesize these compounds so that the properties and activities
can be further investigated.
In our previous work,[5,6] a method to prepare N-aryl-5-aryl-2-furoyl
amides had been introduced. In that method, the 5-aryl-2-furoic acids were
converted into 5-aryl-2-furoyl chlorides first, and followed to react with
arylamines under liquid–liquid phase transfer catalysis using polyethylene
glycol-400 (PEG-400) as catalyst and sodium hydroxide as base. However,
this method not only leads to more steps, but also brings other side reactions
especially for carboxylic acid bearing substituents which are active to acids
and bases. In this paper we report an one pot method to synthesize a new
series of N-aryl-5-aryl-2-furoyl amides from corresponding carboxylic acids
and amines under solid–liquid phase transfer catalysis using PEG-400 as
catalyst and potassium carbonate as base.
Reaction of 5-aryl-2-furoic acids (1) with potassium carbonate and
phenylsulfonyl chloride catalyzed by PEG-400 gives a mixed anhydrides
(2) as intermediates. Compounds 2 on treatment with arylamines in situ
afford N-aryl-5-aryl-2-furoyl amides (3a–r) (Sch. 1). The yields of all
compounds 3a–r are shown in Table 1.
PEG-400 used in these reactions plays a very important role in the first
step. It can easily form complex (PEG-400-Kþ)FuCOOÀ (here Fu is 5-aryl-
2-furyl). This complex makes the FuCOOÀ possible to readily react with
phenylsulfonyl chloride to give compounds 2. In contrast, if no PEG-400 is
used, there are no any compounds 2 formed at all.
The compound 2 includes a very easily leaving group, PhSO3, and can
readily react with arylamines to give 3a–r by eliminating PhSO3H although
the arylamines are weak nucleophilic substitution reagents.
The described method above can be extended to the preparation of
various aromatic and aliphatic carboxamides.
The characterization of compounds 3a–r is based on their IR (KBr),
1H NMR MS and elemental analyses. The IR spectra exhibit characteristic
Scheme 1.

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N-ARYL-5-ARYL-2-FUROYL AMIDES
Table 1. The Isolated Yields of 3a–r
3359
Compd.
Ar
R
Yield Compd.
Ar
R
Yield
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5
2-CH3C6H4
2-CH3OC6H4 2-O2N
2-O2N
2-O2N
90
92
90
86
87
89
86
89
88
3j
3k
3l
3m
3n
3o
3p
3q
3r
C6H5
2-CH3C6H4
2-CH3OC6H4 3-O2N
3-O2N
3-O2N
91
89
96
90
92
93
93
96
90
1-Naphthyl
2-ClC6H4
4-BrC6H4
2-O2N
2-O2N
2-O2N
2-O2N
2-O2N
2-O2N
1-Naphthyl
2-ClC6H4
4-BrC6H4
3-O2N
3-O2N
3-O2N
3-O2N
3-O2N
3-O2N
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
strong absorption at 1654–1685 cmÀ1 attributable to the carbonyl of 3a–r.
1
NH absorptions are observed at 3310–3330 cmÀ1. The H NMR spectral
data of 3a–r in d6-dimethylsulfoxide show peaks at 10.14–10.52 for
proton of NH. All elemental analyses and MS of 3a–r are good agreement
with the structure prepared.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on an Alpha Centauri FT-IR
1
spectrophotometer and H NMR spectra on a FT-80A instrument using
DMSO-d6 as solvent and Me4Si as internal standard. Elemental analyses
were performed on a Vario EI 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-Aryl-2-furoic acid (1) was prepared according to literature procedure.[7]
Arylamines, phenylsulfonyl chloride and PEG-400 were commercially
available and used as received.
General Procedure for the Preparation of Compounds 3a–r
The mixture of 5 mmol of 5-aryl-2-furoic acid (1), 5 mmol (0.88 g) of
PhSO2Cl and 20 mmol (2.76 g) of anhydrous K2CO3, 0.15 mmol (0.06 g)
of PEG-400 in 15 mL of CH3CN was refluxed for 0.5 h. Then 5 mmol of
arylamine was added, and the resulting mixture was refluxed for another 1 h.
The solvent was removed by evaporation. To the residue, 10 mL of water
was added so that the inorganic salts were dissolved, then the slurry was

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3360
LI AND WANG
filtered, the solid was washed with 2 Â 5 mL water and recrystallized from
DMF-H2O (3 : 1), and the product was given. The yield of the product was
calculated according to the compound 1. The physical and spectral data of
compounds 3a–r are reported below.
N-Phenyl-5-(2-nitrophenyl)-2-furoyl amide (3a): White solid. M.p.:
123–124ꢀC. H NMR (DMSO-d6) ꢀ 10.30 (s, 1H, NH), 7.15–8.30 (m, 11H,
1
Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3320 (NH), 1656 (C¼O). MS: m/z, 308
(Mþ). Anal. calcd. for C17H12N2O4: C, 66.23; H, 3.92; N, 9.09. Found: C,
66.03; H, 3.86; N, 8.90.
N-(2-Methylphenyl)-5-(2-nitrophenyl)-2-furoyl amide (3b): White solid.
M.p.: 136–137ꢀC. 1H NMR (DMSO-d6) ꢀ 10.14 (s, 1H, NH), 7.28–8.31
(m, 10H, Ar-H and Fu-H), 2.26 (s, 3H, CH3). IR (KBr, ꢁ, cmÀ1): 3315
(NH), 1654 (C¼O). MS: m/z, 322 (Mþ). Anal. calcd. for C18H14N2O4: C,
67.07; H, 4.38; N, 8.69. Found: C, 67.20; H, 4.43; N, 8.76.
N-(2-Methoxylphenyl)-5-(2-nitrophenyl)-2-furoyl amide (3c): White
solid. M.p.: 119–120ꢀC. 1H NMR (DMSO-d6) ꢀ 10.22 (s, 1H, NH),
7.20–8.24 (m, 10H, Ar-H and Fu-H), 3.74 (s, 3H, CH3). IR (KBr, ꢁ, cmÀ1):
3320 (NH), 1664 (C¼O). MS: m/z, 338 (Mþ). Anal. calcd. for C18H14N2O5:
C, 63.90; H, 4.17; N, 8.28. Found: C, 64.01; H, 4.25; N, 8.39.
N-Naphthyl-5-(2-nitrophenyl)-2-furoyl amide (3d): White solid. M.p.:
127–128ꢀC. H NMR (DMSO-d6) ꢀ 10.51 (s, 1H, NH), 7.27–8.30 (m, 13H,
1
Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3278 (NH), 1657 (C¼O). MS: m/z, 358
(Mþ). Anal. calcd. for C21H14N2O4: C, 70.39; H, 3.94; N, 7.82. Found: C,
70.50; H, 4.01; N, 7.89.
N-(2-Chlorophenyl)-5-(2-nitrophenyl)-2-furoyl amide (3e): White solid.
M.p.: 151–152ꢀC. 1H NMR (DMSO-d6) ꢀ 10.24 (s, 1H, NH), 7.20–8.18
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3328 (NH), 1666 (C¼O).
MS: m/z, 342 (Mþ). Anal. calcd. for C17H11N2O4Cl: C, 59.57; H, 3.23;
N, 8.17. Found: C, 59.70; H, 3.30; N, 8.30.
N-(4-Bromophenyl)-5-(2-nitrophenyl)-2-furoyl amide (3f ): White solid.
M.p.: 159–160ꢀC. 1H NMR (DMSO-d6) ꢀ 10.16 (s, 1H, NH), 7.23–8.26
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3326 (NH), 1684 (C¼O).
MS: m/z, 387 (Mþ). Anal. calcd. for C17H11N2O4Br: C, 52.74; H, 2.86; N,
7.24. Found: C, 52.64; H, 2.90; N, 7.34.
N-(2-Nitrophenyl)-5-(2-nitrophenyl)-2-furoyl amide (3g): White solid.
M.p.: 131–132ꢀC. 1H NMR (DMSO-d6) ꢀ 10.41 (s, 1H, NH), 7.12–8.29
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3310 (NH), 1658 (C¼O).
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.68; H, 3.02; N, 11.79.
N-(3-Nitrophenyl)-5-(2-nitrophenyl)-2-furoyl amide (3h): White solid.
M.p.: 173–174ꢀC. 1H NMR (DMSO-d6) ꢀ 10.29 (s, 1H, NH), 7.13–8.30
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3318 (NH), 1660 (C¼O).

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N-ARYL-5-ARYL-2-FUROYL AMIDES
3361
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.89; H, 3.17; N, 11.98.
N-(4-Nitrophenyl)-5-(2-nitrophenyl)-2-furoyl Amide (3i): White solid.
M.p.: 183–184ꢀC. 1H NMR (DMSO-d6) ꢀ 10.50 (s, 1H, NH), 7.10–8.32
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3316 (NH), 1654 (C¼O).
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.92; H, 3.20; N, 12.01.
N-Phenyl-5-(3-nitrophenyl)-2-furoyl amide (3j): White solid. M.p.:
136–137ꢀC. H NMR (DMSO-d6) ꢀ 10.32 (s, 1H, NH), 7.13–8.31 (m, 11H,
1
Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3324 (NH), 1658 (C¼O). MS: m/z,
308 (Mþ). Anal. calcd. for C17H12N2O4: C, 66.23; H, 3.92; N, 9.09. Found:
C, 66.31; H, 4.05; N, 9.18.
N-(2-Methylphenyl)-5-(3-nitrophenyl)-2-furoyl amide (3k): White solid.
M.p.: 143–144ꢀC. 1H NMR (DMSO-d6) ꢀ 10.15 (s, 1H, NH), 6.90–8.07
(m, 10H, Ar-H and Fu-H), 2.27 (s, 3H, CH3). IR (KBr, ꢁ, cmÀ1): 3320
(NH), 1657 (C¼O). MS: m/z, 322 (Mþ). Anal. calcd. for C18H14N2O4:
C, 67.07; H, 4.38; N, 8.69. Found: C, 67.18; H, 4.41; N, 8.79.
N-(2-Methoxylphenyl)-5-(3-nitrophenyl)-2-furoyl amide (3l): White
solid. M.p.: 159–160ꢀC. 1H NMR (DMSO-d6) ꢀ 10.21 (s, 1H, NH),
7.22–8.21 (m, 10H, Ar-H and Fu-H), 3.76 (s, 3H, CH3). IR (KBr, ꢁ, cmÀ1):
3322 (NH), 1659 (C¼O). MS: m/z, 338 (Mþ). Anal. calcd. for C18H14N2O5:
C, 63.90; H, 4.17; N, 8.28. Found: C, 63.72; H, 4.13; N, 8.16.
N-Naphthyl-5-(3-nitrophenyl)-2-furoyl amide (3m): White solid. M.p.:
144–145ꢀC. H NMR (DMSO-d6) ꢀ 10.48 (s, 1H, NH), 7.24–8.26 (m, 13H,
1
Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3281 (NH), 1659 (C¼O). MS: m/z, 358
(Mþ). Anal. calcd. for C21H14N2O4: C, 70.39; H, 3.94; N, 7.82. Found:
C, 70.48; H, 4.01; N, 7.92.
N-(2-Chlorophenyl)-5-(3-nitrophenyl)-2-furoyl amide (3n): White solid.
M.p.: 156–157ꢀC. 1H NMR (DMSO-d6) ꢀ 10.25 (s, 1H, NH), 7.19–8.22
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3330 (NH), 1664 (C¼O).
MS: m/z, 342 (Mþ). Anal. calcd. for C17H11N2O4Cl: C, 59.57; H, 3.23;
N, 8.17. Found: C, 59.49; H, 3.19; N, 8.09.
N-(4-Bromophenyl)-5-(3-nitrophenyl)-2-furoyl amide (3o): White solid.
93%. M.p.: 203–204ꢀC. 1H NMR (DMSO-d6) ꢀ 10.18 (s, 1H, NH),
7.22–8.25 (m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3328 (NH), 1685
(C¼O). MS: m/z, 387 (Mþ). Anal. calcd. for C17H11N2O4Br: C, 52.74;
H, 2.86; N, 7.24. Found: C, 52.80; H, 2.90; N, 7.31.
N-(2-Nitrophenyl)-5-(3-nitrophenyl)-2-furoyl amide (3p): White solid.
M.p.: 173–174ꢀC. 1H NMR (DMSO-d6) ꢀ 10.43 (s, 1H, NH), 7.18–8.31
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3312 (NH), 1660 (C¼O).
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.73; H, 3.06; N, 11.98.

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LI AND WANG
N-(3-Nitrophenyl)-5-(3-nitrophenyl)-2-furoyl amide (3q): White solid.
M.p.: 191–192ꢀC. 1H NMR (DMSO-d6) ꢀ 10.30 (s, 1H, NH), 7.10–8.32
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3320 (NH), 1658 (C¼O).
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.90; H, 3.20; N, 11.74.
N-(4-Nitrophenyl)-5-(3-nitrophenyl)-2-furoyl amide (3r): White solid.
M.p.: 208–209ꢀC. 1H NMR (DMSO-d6) ꢀ 10.52 (s, 1H, NH), 7.15–8.30
(m, 10H, Ar-H and Fu-H). IR (KBr, ꢁ, cmÀ1): 3318 (NH), 1656 (C¼O).
MS: m/z, 353 (Mþ). Anal. calcd. for C17H11N3O6: C, 57.80; H, 3.14;
N, 11.89. Found: C, 57.94; H, 3.19; N, 12.00.
ACKNOWLEDGMENTS
The authors thank the Scientific and Technological Innovation
Engineering of Northwest Normal University, Natural Science Foundation
of Gansu Province and Youth Foundation of Northwest Normal University
for the financial support of this work.
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Received in Japan April 25, 2001