An expeditious room-temperature grinding method to 5-aryl-2-furoyl substituted thioureas and thiosemicarbazides

Article abstract of DOI:10.1081/SCC-120030690

An expeditious, one-pot, high-yielding and solventless approach to 5-aryl-2-furoyl substituted thioureas and thiosemicarbazides by room-temperature grinding method is described.

Full text of DOI:10.1081/SCC-120030690

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An Expeditious Room‐Temperature Grinding Method
to 5‐Aryl‐2‐furoyl Substituted Thioureas and
Thiosemicarbazides
Zhang Zhang a , Xicun Wang a & Zheng Li a b
a College of Chemistry and Chemical Engineering , Northwest Normal University ,
Lanzhou, Gansu, 730070, P.R. China
b School of Chemical and Biological Engineering , Lanzhou Jiaotong University , Lanzhou,
Gansu, P.R. China
Published online: 21 Aug 2006.
To cite this article: Zhang Zhang , Xicun Wang & Zheng Li (2004) An Expeditious Room‐Temperature Grinding Method to
5‐Aryl‐2‐furoyl Substituted Thioureas and Thiosemicarbazides, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:8, 1407-1414, DOI: 10.1081/SCC-120030690
To link to this article: http://dx.doi.org/10.1081/SCC-120030690
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 8, pp. 1407–1414, 2004
An Expeditious Room-Temperature
Grinding Method to 5-Aryl-2-furoyl
Substituted Thioureas and
Thiosemicarbazides
Zhang Zhang,1 Xicun Wang,1 and Zheng Li1,2,,
*
1College of Chemistry and Chemical Engineering, Northwest Normal
University, Lanzhou, Gansu, P.R. China
2School of Chemical and Biological Engineering, Lanzhou Jiaotong
University, Lanzhou, Gansu, P.R. China
ABSTRACT
An expeditious, one-pot, high-yielding and solventless approach to
5-aryl-2-furoyl substituted thioureas and thiosemicarbazides by room-
temperature grinding method is described.
Key Words: Thiourea; Thiosemicarbazide; Solventless; Grinding.
*
Correspondence: Zheng Li, College of Chemistry and Chemical Engineering, North-
west Normal University, Lanzhou, Gansu 730070, P.R. China; E-mail: lizheng@nwnu.
edu.cn.
1407
DOI: 10.1081/SCC-120030690
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Zhang, Wang, and Li
INTRODUCTION
The development of solvent-free organic synthesis is of current interest
because of the many advantages, such as reduced pollution, low cost,
simplicity in process and handling, potential applications in combinatorial
chemistry and chemical industry.[1]
Substituted thioureas and thiosemicarbazides have attracted much atten-
tion in recent years because of their anti-HIV,[2] bactericidal,[3] and tuberculo-
static[4] activities, and their importance in the preparation of corresponding
semicarbazides,[5] metal complexes,[6] and heterocyclic compounds.[7–9]
The existing synthetic methods for substituted thioureas and thiosemicar-
bazides have to conduct the reactions for extended period in the volatile
and noxious organic solvents (methylene chloride or acetonitrile).[10–12]
Therefore, there is still a need to investigate a new approach to overcome
the above drawbacks. In continuation of our ongoing program to synthesize
biologically active compounds and develop benign and rapid strategy for
organic transformation under solventless conditions and the interest in green
chemistry theme with growing emphasis on pollution prevention, we have
explored an expeditious, one-pot and solvent-free route to prepare 5-aryl-
2-furoyl substituted thioureas and thiosemicarbazides.
5-(20-Nitrophenyl)-2-furoyl chloride (1) was ground with ammonium
thiocyanate in the presence of poly(ethylene glycol)-400 (PEG-400) in a
mortar at room temperature until the acid chloride 1 disappeared and
5-(20-nitrophenyl)-2-furoyl isothiocyanate (2) was formed according to TLC
analysis. In this reaction, PEG-400 acted as a catalyst, which can readily
form the complex (PEG-400-NH4)þSCN2 with ammonium thiocyanate to
make the nucleophilic reaction of SCN2 with compound 1 easily take place.
It is noteworthy that the reaction without PEG-400 is unavailable for
compound 2.
Compound 2 was in situ ground with equivalent of arylamines or aryl-
oxyacetic acid hydrazides until the significant color changes were observed
and the products, N-aryl-N0-(5-(20-nitrophenyl)-2-furoyl)-thioureas (3a–l) or
1-aryloxyacetyl-4-(50-(200-nitrophenyl)-20-furoyl)-thiosemicarbazides (4a–k),
were formed. The completion of the reaction was monitored by TLC.
Compound 3a–l and 4a–k, those are of acceptable purity for most purpose,
were given in excellent yield only by washing the resulting solids using
water. Furthermore, the by-product, ammonium chloride, can also be easily
recovered from the aqueous solution by evaporation. The overall reaction
can be completed within 8 min in 82–99% yield (Sch. 1). The results are
shown in Table 1 and 2.
In conclusion, the title compounds can be expeditiously synthesized via
room-temperature grinding method by one-pot procedure under solvent-free

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5-Aryl-2-furoyl Substituted Thioureas and Thiosemicarbazides
1409
Scheme 1.
Table 1. Solvent-free preparation of 3a–l and 4a–k by grinding method.
Reaction
time (min)
Compound
Ar
M.p. (8C)
Yield (%)a
3a
3b
3c
3d
3e
3f
C6H5
4
7
5
5
4
4
4
5
4
4
3
5
5
4
4
5
5
4
5
5
6
3
8
142–143
167–168
158–159
139–140
152–153
169–170
179–180
198–199
208–209
192–193
198–199
176–177
196–197
198–199
195–196
185–186
237–238
246–247
196–197
202–203
209–210
201–202
222–223
92
88
89
99
98
93
95
93
92
98
99
88
98
84
99
82
83
82
95
86
99
99
98
2-CH3C6H4
4-CH3C6H4
2-ClC6H4
4-ClC6H4
2-O2NC6H4
3-O2NC6H4
2-CH3OC6H4
4-CH3COC6H4
2,4,6-Br3C6H2
1-Naphthyl
2-Naphthyl
C6H5
3g
3h
3i
3j
3k
3l
4a
4b
4c
4d
4e
4f
2-CH3C6H4
4-CH3C6H4
4-CH3OC6H4
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
4-ClC6H4
4g
4h
4i
2,4-Cl2C6H3
1-Naphthyl
2-Naphthyl
4j
4k
aYields refer to the isolated products.

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Zhang, Wang, and Li
Table 2. IR and 1H NMR data of 3a–l and 4a–k.
IR (cm21
)
Compound
N–H
3210
C55O
C55S
1H NMR (DMSO-d6, d)
3a
1670
1152
6.98–8.36 (m, 11H, Ar-H, and
Fu-H), 11.52 (s, 1H, NH), 12.01
(s, 1H, NH)
3b
3c
3d
3e
3f
3201
3208
3219
3220
3218
3221
3198
1673
1669
1671
1673
1670
1668
1665
1156
1154
1160
1162
1155
1160
1157
2.27 (s, 3H, CH3), 7.09–8.30
(m, 10H, Ar-H, and Fu-H), 11.57
(s, 1H, NH), 12.04 (s, 1H, NH)
2.28 (s, 3H, CH3), 7.10–8.32
(m, 10H, Ar-H, and Fu-H), 11.56
(s, 1H, NH), 12.03 (s, 1H, NH)
6.91–8.42 (m, 10H, Ar-H, and
Fu-H), 11.62 (s, 1H, NH), 12.08
(s, 1H, NH)
7.11–8.47 (m, 10H, Ar-H, and
Fu-H), 11.64 (s, 1H, NH), 12.09
(s, 1H, NH)
7.10–8.37 (m, 10H, Ar-H, and
Fu-H), 11.77 (s, 1H, NH), 12.58
(s, 1H, NH)
3g
3h
7.08–8.39 (m, 10H, Ar-H, and
Fu-H), 11.69 (s, 1H, NH), 12.55
(s, 1H, NH)
3.38 (s, 3H, CH3), 6.99–8.37
(m, 10H, Ar-H, and Fu-H),
11.67 (s, 1H, NH), 12.43
(s, 1H, NH)
3i
3208
3355
3221
3223
1670
1689
1678
1681
1156
1149
1152
1151
2.54 (s, 3H, CH3), 7.32–8.31
(m, 10H, Ar-H, and Fu-H), 11.60
(s, 1H, NH), 12.28 (s, 1H, NH)
7.21–8.32 (m, 8H, Ar-H, and
Fu-H), 11.78 (s, 1H, NH) 12.60
(s, 1H, NH)
3j
3k
3l
7.12–8.04 (m, 12H, Ar-H, and
Fu-H), 11.61 (s, 1H, NH) 12.34
(s, 1H, NH)
7.10–8.12 (m, 12H, Ar-H, and
Fu-H), 11.52 (s, 1H, NH) 12.31
(s, 1H, NH)
(continued)

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5-Aryl-2-furoyl Substituted Thioureas and Thiosemicarbazides
1411
Table 2. Continued.
IR (cm21
)
Compound
N–H
C55O
C55S
1H NMR (DMSO-d6, d)
4a
3278
3173
1697
1670
1163
4.98 (s, 2H, OCH2), 7.10–8.23
(m, 11H, Ar-H, and Fu-H), 11.01
(s, 1H, NH), 11.78 (s, 1H, NH),
12.28 (s, 1H, NH)
4b
4c
4d
3290
3154
1701
1672
1166
1165
1167
2.28 (s, 3H, CH3), 5.03 (s, 2H,
OCH2), 6.98–8.20 (m, 10H, Ar-H,
and Fu-H) 10.99 (s, 1H, NH),
11.72 (s, 1H, NH), 12.40 (s, 1H,
NH)
3284
3134
1674
1668
2.27 (s, 3H, CH3), 4.91 (s, 2H,
OCH2), 7.05–8.19 (m, 10H,
Ar-H, and Fu-H), 10.97 (s, 1H,
NH), 11.76 (s, 1H, NH), 12.38
(s, 1H, NH)
3304
3146
1684
1672
3.51 (s, 3H, CH3), 4.96 (s, 2H,
OCH2), 7.11–8.27 (m, 10H,
Ar-H, and Fu-H), 10.99 (s, 1H,
NH), 11.81 (s, 1H, NH), 12.40
(s, 1H, NH)
4e
4f
3268
3174
1676
1663
1166
1172
1169
1165
5.04 (s, 2H, OCH2), 7.12–8.36
(m, 10H, Ar-H and Fu-H), 11.12
(s, 1H, NH), 11.82 (s, 1H, NH),
12.56 (s, 1H, NH)
3287
3170
1700
1670
5.01 (s, 2H, OCH2), 7.16–8.28
(m, 10H, Ar-H, and Fu-H), 11.08
(s, 1H, NH), 11.75(s, 1H, NH),
12.60 (s, 1H, NH)
4g
4h
3301
3264
1690
1672
4.99 (s, 2H, OCH2), 7.29–8.30
(m, 10H, Ar-H, and Fu-H), 11.06
(s, 1H, NH), 11.97 (s, 1H, NH),
12.58 (s, 1H, NH)
3298
3157
1679
1665
5.00 (s, 2H, OCH2), 7.09–8.30
(m, 10H, Ar-H, and Fu-H), 11.06
(s, 1H, NH), 11.70 (s, 1H, NH),
12.36 (s, 1H, NH)
(continued)

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Zhang, Wang, and Li
Table 2. Continued.
IR (cm21
)
Compound
N–H
C55O
C55S
1H NMR (DMSO-d6, d)
4i
3280
3163
1674
1665
1170
5.01 (s, 2H, OCH2), 7.03–8.23
(m, 9H, Ar-H, and Fu-H), 11.07
(s, 1H, NH), 11.82 (s, 1H, NH),
12.48 (s, 1H, NH)
4j
3285
3137
1680
1668
1165
1164
4.94 (s, 2H, OCH2), 7.01–8.36
(m, 13H, Ar-H, and Fu-H), 11.11
(s, 1H, NH), 11.81 (s, 1H, NH),
12.35 (s, 1H, NH)
4k
3276
3160
1684
1670
5.01 (s, 2H, OCH2), 7.04–8.34
(m, 13H, Ar-H, and Fu-H), 11.02
(s, 1H, NH), 11.83 (s, 1H, NH),
12.31 (s, 1H, NH)
condition in excellent yield. The features of no use of any hazardous solvents,
high rate, and easy handling make this protocol to become a “green” and
universal method for the preparation of substituted thioureas and
thiosemicarbazides.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on a Nicolet AVATAR 360
FT-IR spectrophotometer and 1H NMR spectra on a Avanci-D2X-200 instru-
ment using (CD3)2SO as solvent and Me4Si as internal standard. Elemental
analyses were performed on a Vario El Elemental Analysis instrument.
Melting points were observed in an open capillary tube and uncorrected.
5-(20-Nitrophenyl)-2-furoyl chloride (1),[13] aryloxyacetic acid hydrazides[14]
were prepared according to literature procedures.
General Procedure for Preparation of 3a–l and 4a–k
The mixture of 5-(20-nitrophenyl)-2-furoyl chloride (1) (0.5 mmol),
ammonium thiocyanate (0.5 mmol) and PEG-400 (0.02 mmol) was ground
in an agate mortar with a pestle for 2 min, until a yellow solid was

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5-Aryl-2-furoyl Substituted Thioureas and Thiosemicarbazides
1413
formed, and TLC (ethyl acetate-benzene-ethyl ether 2 : 1 : 1 as eluent)
indicated the disappearance of 1. Then arylamine or aryloxyacetic acid hydra-
zide (0.5 mmol) was added, and the mixture was further ground for 1–6 min
until a color change was observed. The completion of reaction was monitored
by TLC using acetone as eluent. Then the resulting solid was washed with
distilled water (10 mL) and the product was afforded as solid. The analytic
sample was obtained by recrystallization from DMF-EtOH-H2O (6 : 3 : 1).
ACKNOWLEDGMENT
The authors thank the Scientific and Technological Innovation Engineer-
ing of Northwest Normal University (NWNU-KJCXGC-02-08), Natural
Science Foundation of Gansu Province (ZS021-A25-006-Z), Environmental
Protection Foundation of Gansu Province (GH2002-16) for the financial
support of this work.
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Zhang, Wang, and Li
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Received in Japan September 30, 2003

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