Synthesis of 1-aryloxyacetyl-4-(4-nitrobenzoyl)-thiosemicarbazides under phase transfer catalysis and microwave irradiation

Article abstract of DOI:10.1081/SCC-120013717

The 1-aryloxyacetyl-4-(4-nitrobenzoyl)-thiosemicarbazides (3a-m) are synthesized via reaction of 4-nitrobenzoyl chloride with ammonium thiocyanate and aryloxyacetic acid hydrazides (2a-m) under phase transfer catalysis and microwave irradiation in excelle

Full text of DOI:10.1081/SCC-120013717

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SYNTHESIS OF 1-ARYLOXYACETYL- 4-(4-
NITROBENZOYL)-THIOSEMICARBAZIDES UNDER PHASE
TRANSFER CATALYSIS AND MICROWAVE IRRADIATION
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) SYNTHESIS OF 1-ARYLOXYACETYL- 4-(4-NITROBENZOYL)-
THIOSEMICARBAZIDES UNDER PHASE TRANSFER CATALYSIS AND MICROWAVE IRRADIATION, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:20, 3087-3092, DOI: 10.1081/
SCC-120013717
To link to this article: http://dx.doi.org/10.1081/SCC-120013717
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 20, pp. 3087–3092, 2002
SYNTHESIS OF 1-ARYLOXYACETYL-
4-(4-NITROBENZOYL)-
THIOSEMICARBAZIDES UNDER PHASE
TRANSFER CATALYSIS AND
MICROWAVE IRRADIATION
*
Zheng Liand Xciun Wang
College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou,
Gansu, 730070, P.R. China
ABSTRACT
The
1-aryloxyacetyl-4-(4-nitrobenzoyl)-thiosemicarbazides
(3a–m) are synthesized via reaction of 4-nitrobenzoyl chloride
with ammonium thiocyanate and aryloxyacetic acid hydra-
zides (2a–m) under phase transfer catalysis and microwave
irradiation in excellent yield.
1,4-Diacyl thiosemicarbazides have attracted much attention in recent
years because of their fungicidal,[1,2] bactericidal[3,4] and tuberculostatic[5,6]
activities. Meanwhile, aryloxyacetic acid derivatives have also been used as
herbicides and plant-growth regulators.[7–10] These applications prompt us
to synthesize a new series of compounds bearing both thiosemicarbazide
*Corresponding author. E-mail: lizheng@nwnu.edu.cn
3087
DOI: 10.1081/SCC-120013717
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3088
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Scheme 1.
and aryloxyacetyl moiety, with the objective of obtaining new biologically
active compounds.
Recently we have synthesized some 1,4-diacyl thiosemicarbazides under
phase transfer catalysis.[11–18] However, in this paper, we report a convenient
and efficient method for the preparation of a series of new 1,4-diacyl
thiosemicarbazides under solid–liquid phase transfer catalysis and micro-
wave irradiation.
Reaction of 4-nitrobenzoyl chloride with ammonium thiocyanate using
polyethylene glycol-400 (PEG-400) as phase transfer catalyst under 600 W
microwave irradiation for 9 min, the 4-nitrobenzoyl thioisocyanate (1) is
given as intermediate, which in situ reacts with aryloxyacetic acid hydrazides
(2a–m) under 675 W microwave irradiation for 4 min to afford 1-aryloxyace-
tyl-4-(4-nitrobenzoyl)-thiosemicarbazides (3a–m) in excellent yield (Sch. 1).
PEG-400 as phase transfer catalyst is indispensable for these reactions.
It can easily react with NH4SCN to form complex [PEG-400-NHþ4 ]SCNÀ,
which makes the SCNÀ possible to readily react with 4-nitrobenzoyl chlor-
ide and lead to the formation of intermediate 1. However, if no PEG-400 is
used, there is no intermediate 1 formed, therefore no any target compound
3a–m are produced at all.
DMF used in these reactions can obviously improve the yield of 3a–m
in terms of two reasons: one is DMF as a polar nonproton solvent can
promote the formation of active SCNÀ and the nucleophilic substitution
of SCNÀ; the other is DMF as a high dielectric constant solvent is favorable
to the efficient absorption of microwave irradiation.
The microwave method used in this paper has the advantage of short
reaction time and high reaction yield compared to the conventional
method.[11–18] In addition, this method can also be extended to the
preparation of other 1,4-diacyl thiosemicarbazides.

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PHASE TRANSFER CATALYSIS
3089
The characterization of compounds 3a–m in based on their IR (KBr),
1H NMR, MS and elemental analyses. The IR spectra exhibit a characteristic
strong absorption at 1162–1194 cmÀ1 attributable to the C¼S. The cabonyl
1
absorption is observed at 1655–1710 cmÀ1. The H NMR spectral data in
d6-dimethylsulfoxide show peaks at 12.29–12.84 (NH), 11.89–12.09 (NH),
10.01–11.15 (NH) and 4.69–5.06 ppm (CH2). All elemental analyses and
MS are good agreement with the structure prepared.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on an Alpha Centauri
1
FTIR spectrophotometer and H NMR spectra on a FT-80A instrument
using (CD3)2SO as solvent and Me4Si as internal standard. Elemental
analyses were performed on a Vario E1 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. 4-Nitrobenzoyl chloride[19] and aryloxyacetic acid
hydrazides[20] were prepared according to literature procedure. Ammonium
thiocyanate and PEG-400 were commercially available and used as
received.
General Procedure for the Preparation of Compounds 3a–m
To a solution of 4-nitrobenzoyl chloride (0.56 g, 3.0 mmol) in 15 mL
of CHCl3 and 2 drops of DMF, NH4SCN (0.34 g, 4.5 mmol) and PEG-400
(0.04 g, 0.1 mmol) were added. The mixture was exposed on 600 W of
microwave irradiation for 9 min. Then aryloxyacetic acid hydrazide
(3.0 mmol) was added and the reaction mixture was exposed on 675 W
of microwave irradiation for 4 min again. The resulting mixture was
evaporated to remove part of solvent, and the residue was poured into
H2O (10 mL). After the filtration, the solid was recrystallized from DMF-
C2H5OH-H2O (6 : 3 : 1) to give product. The physical and spectral results
of 3a–m were shown below.
1-Phenyloxyacetyl-4-(4-nitrobenzoyl)-thiosemicarbazide (3a): White
solid. Yield: 88%. M.p.: 243–244ꢀC. H NMR (DMSO-d6) ꢀ 12.36 (1H, s,
1
NH), 11.98 (1H, s, NH), 11.03 (1H, s, NH), 6.83–8.29 (9H, m, ArH), 4.69
(2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3292 (N-H), 1698, 1679 (C¼O), 1168
(C¼S). MS: m/z, 374 (Mþ). Anal. Calcd. for C16H14N4O5S: C, 51.33; H,
3.77; N, 14.97. Found: C, 51.18; H, 3.59; N, 15.13.

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LI AND WANG
1-(2-Methylphenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3b):
White solid. Yield: 86%. M.p.: 271–272ꢀC. H NMR (DMSO-d6) ꢀ 12.31
(1H, s, NH), 11.96 (1H, s, NH), 10.95 (1H, s, NH), 6.61–8.42 (8H, m,
ArH), 4.70 (2H, s, CH2), 2.29 (3H, s, CH3). IR (KBr, ꢁ, cmÀ1): 3228 (N-H),
1700, 1678 (C¼O), 1189 (C¼S). MS: m/z, 388 (Mþ). Anal. Calcd. for
C17H16N4O5S: C, 52.57; H, 4.15; N, 14.42. Found: C, 52.44; H, 4.11; N, 14.87.
1-(3-Methylphenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3c):
1
White solid. Yield: 94%. M.p.: 210–211ꢀC. H NMR (DMSO-d6) ꢀ 12.30
1
(1H, s, NH), 11.97 (1H, s, NH), 10.98 (1H, s, NH), 6.72–8.37 (8H, m, ArH),
4.72 (2H, s, CH2), 2.30 (3H, s, CH3). IR (KBr, ꢁ, cmÀ1): 3231 (N-H), 1699,
1678 (C¼O), 1194 (C¼S). MS: m/z, 388 (Mþ). Anal. Calcd. for
C17H16N4O5S: C, 52.57; H, 4.15; N, 14.42. Found: C, 52.58; H, 4.12;
N, 14.68.
1-(4-Methylphenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3d):
White solid. Yield: 91%. M.p.: 203–204ꢀC. H NMR (DMSO-d6) ꢀ 12.29
1
(1H, s, NH), 12.00 (1H, s, NH), 10.96 (1H, s, NH), 6.74–8.40 (8H, m, ArH),
4.71 (2H, s, CH2), 2.32 (3H, s, CH3). IR (KBr, ꢁ, cmÀ1): 3293, 3150
(N-H), 1692, 1667 (C¼O), 1158 (C¼S). MS: m/z, 388 (Mþ). Anal. Calcd.
for C17H16N4O5S: C, 52.57; H, 4.15; N, 14.42. Found: C, 52.60; H, 4.13;
N, 14.58.
1-(4-Methoxylphenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide
(3e): White solid. Yield: 87%. M.p.: 201–202ꢀC. 1H NMR (DMSO-d6)
ꢀ 12.29 (1H, s, NH), 11.89 (1H, s, NH), 10.98 (1H, s, NH), 6.70–8.29
(8H, m, ArH), 4.70 (2H, s, CH2), 3.47 (3H, s, CH3). IR (KBr, ꢁ, cmÀ1):
3298, 3282 (N-H), 1701, 1695 (C¼O), 1162 (C¼S). MS: m/z, 404 (Mþ).
Anal. Calcd. for C17H16N4O6S: C, 50.49; H, 3.99; N, 13.85. Found: C,
50.46; H, 3.89; N, 13.73.
1-(2-Chlorophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3f):
White solid. Yield: 82%. M.p.: 238–239ꢀC. H NMR (DMSO-d6) ꢀ 12.70
1
(1H, s, NH), 12.02 (1H, s, NH), 11.04 (1H, s, NH), 6.79–8.26 (8H, m, ArH),
4.88 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3268 (N-H), 1699, 1676 (C¼O), 1164
(C¼S). MS: m/z, 408 (Mþ). Anal. Calcd. for C16H13N4O5SCl: C, 47.01; H,
3.21; N, 13.70. Found: C, 47.06; H, 3.18; N, 13.46.
1-(4-Chlorophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3g):
White solid. Yield: 88%. M.p.: 263–264ꢀC. H NMR (DMSO-d6) ꢀ 12.71
1
(1H, s, NH), 12.01 (1H, s, NH), 11.01 (1H, s, NH), 6.83–8.26 (8H, m, ArH),
4.89 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3307, 3150 (N-H), 1692, 1655 (C¼O),
1174 (C¼S). MS: m/z, 408 (Mþ). Anal. Calcd. for C16H13N4O5SCl: C, 47.01;
H, 3.21; N, 13.70. Found: C, 47.18; H, 3.13; N, 13.37.
1-(2,4-Dichlorophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide
(3h): White solid. Yield: 90%. M.p.: 218–219ꢀC. 1H NMR (DMSO-d6) ꢀ 12.74
(1H, s, NH), 12.04 (1H, s, NH), 11.05 (1H, s, NH), 6.90–8.23 (7H, m, ArH),

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PHASE TRANSFER CATALYSIS
3091
4.92 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3254 (N-H), 1698, 1675 (C¼O), 1162
(C¼S). MS: m/z, 443 (Mþ). Anal. Calcd. for C16H12N4O5SCl2: C, 43.35; H,
2.73; N, 12.64. Found: C, 43.15; H, 2.61; N, 12.75.
1-(1-Naphthyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3i): White
solid. Yield: 86%. M.p.: 218–219ꢀC. H NMR (DMSO-d6) ꢀ 12.36 (1H, s,
1
NH), 11.95 (1H, s, NH), 10.01 (1H, s, NH), 6.94–8.30 (11H, m, ArH), 4.80
(2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3247 (N-H), 1701, 1672 (C¼O), 1174
(C¼S). MS: m/z, 424 (Mþ). Anal. Calcd. for C20H16N4O5S: C, 56.60; H,
3.80; N, 13.20. Found: C, 56.42; H, 3.68; N, 13.26.
1-(2-Naphthyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3j): White
solid. Yield: 89%. M.p.: 231–232ꢀC. H NMR (DMSO-d6) ꢀ 12.41 (1H, s,
1
NH), 11.96 (1H, s, NH), 10.03 (1H, s, NH), 6.96–8.29 (11H, m, ArH), 4.79
(2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3243 (N-H), 1700, 1673 (C¼O), 1178
(C¼S). MS: m/z, 424 (Mþ). Anal. Calcd. for C20H16N4O5S: C, 56.60; H,
3.80; N, 13.20. Found: C, 56.62; H, 3.76; N, 13.44.
1-(2-Nitrophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3k):
White solid. Yield: 90%. M.p.: 261–262ꢀC. H NMR (DMSO-d6) ꢀ 12.75
1
(1H, s, NH), 12.03 (1H, s, NH), 11.13 (1H, s, NH), 7.10–8.45 (8H, m, ArH),
5.05 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3238 (N-H), 1710, 1677 (C¼O), 1169
(C¼S). MS: m/z, 419 (Mþ). Anal. Calcd. for C16H13N5O7S: C, 45.82; H,
3.12; N, 16.70. Found: C, 45.68; H, 3.02; N, 16.81.
1-(3-Nitrophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3l):
White solid. Yield: 87%. M.p.: 276–277ꢀC. H NMR (DMSO-d6) ꢀ 12.84
1
(1H, s, NH), 12.09 (1H, s, NH), 11.16 (1H, s, NH), 7.08–8.39 (8H, m, ArH),
5.03 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3289, 3226 (N-H), 1703, 1678 (C¼O),
1167 (C¼S). MS: m/z, 419 (Mþ). Anal. Calcd. for C16H13N5O7S: C, 45.82;
H, 3.12; N, 16.70. Found: C, 45.85; H, 3.10; N, 16.96.
1-(4-Nitrophenyloxyacetyl)-4-(4-nitrobenzoyl)-thiosemicarbazide (3m):
White solid. Yield: 95%. M.p.: 281–282ꢀC. H NMR (DMSO-d6) ꢀ 12.80
1
(1H, s, NH), 12.06 (1H, s, NH), 11.15 (1H, s, NH), 7.02–8.36 (8H, m, ArH),
5.06 (2H, s, CH2). IR (KBr, ꢁ, cmÀ1): 3279, 3236 (N-H), 1708, 1676 (C¼O),
1170 (C¼S). MS: m/z, 419 (Mþ). Anal. Calcd. for C16H13N5O7S: C, 45.82;
H, 3.12; N, 16.70. Found: C, 45.74; H, 3.06; N, 16.48.
ACKNOWLEDGMENT
The authors are grateful for financial support for this work from
Scientific and Technological Innovation Engineering of Northwest
Normal University, Natural Science Foundation of Gansu Province and
Youth Foundation of Northwest Normal University.

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Received in Japan May 16, 2001