An efficient solid-state method for the preparation of acyl thiosemicarbazides

Article abstract of DOI:10.1081/SCC-100104325

Solid-state syntheses of acyl thiosemicarbazides are reported for the first time. Eleven acyl thiosemicarbazides have been synthesized at room temperature in excellent yields (84.5 ～ 91.0%). Among them, eight compounds 3a, 3d, 3e, 3g-k are new. The reacti

Full text of DOI:10.1081/SCC-100104325

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AN EFFICIENT SOLID-STATE METHOD FOR THE
PREPARATION OF ACYL THIOSEMICARBAZIDES
Jian-Ping Li a , Qian-Fu Luo a , Yu-Lu Wang a & Hong Wang a
a College of Chemistry and Environmental Science, Henan Normal University, Xinxiang,
453002, China
Published online: 16 Aug 2006.
To cite this article: Jian-Ping Li , Qian-Fu Luo , Yu-Lu Wang & Hong Wang (2001) AN EFFICIENT SOLID-STATE METHOD
FOR THE PREPARATION OF ACYL THIOSEMICARBAZIDES, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:12, 1793-1797, DOI: 10.1081/SCC-100104325
To link to this article: http://dx.doi.org/10.1081/SCC-100104325
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SYNTHETIC COMMUNICATIONS, 31(12), 1793–1797 (2001)
AN EFFICIENT SOLID-STATE METHOD
FOR THE PREPARATION OF ACYL
THIOSEMICARBAZIDES
Jian-Ping Li, Qian-Fu Luo, Yu-Lu Wang,*
and Hong Wang
College of Chemistry and Environmental Science,
Henan Normal University, Xinxiang, 453002, China
Key Laboratory of Environmental Science and Engineering of
Henan Education Commission
ABSTRACT
Solid-state syntheses of acyl thiosemicarbazides are reported
for the first time. Eleven acyl thiosemicarbazides have been
synthesized at room temperature in excellent yields
(84.5 ꢀ 91.0%). Among them, eight compounds 3a, 3d, 3e,
3g–k are new. The reaction proves to be extremely simple
and highly efficient (in 6 ꢀ 18 min).
Acyl thiosemicarbazide compounds exhibit various kinds of biological
activities such as antiviral and antifungal.1 They can be used as insecticides,
herbicides and plant-growth regulators.2 Many of them have potential med-
ical usage3 and some have been tried for the antituberculosis4 and restrain-
ing central nerve.5 Several methods have been developed for the synthesis of
these compounds. The synthesis is usually carried out in solution, requiring
large amounts of volatile and poisonous solvent,6 needing complicated heat-
* Corresponding author. E-mail: hnsdyj@public.xxptt.ha.cn
1793
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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LI ET AL.
ing and stirring apparatus and long reaction times. Herein we describe a new
and efficient method for synthesis of acyl thiosemicarbazides – solid-state
synthesis.
Solid-state organic synthesis has extensive applications. It has many
advantages over conventional solution phase synthesis such as high effi-
ciency and selectivity, easy separation and purification of products, mild
reaction conditions, and environmental acceptability.7 All of these benefits
are in accordance with the requests of green production, saving-energy and
high efficiency. There are a variety of organic syntheses which involve solid-
state reactions.8–11 But the addition of acylhydrazine to aryl isothiocyanates
has not yet been reported.
We have successfully synthesized eleven acyl thiosemicarbazides 3a–k
in excellent yields by the solid-state reaction of 1 and 2 (Scheme). No solvent
or catalyst of complicated glassware is involved, the reaction is performed in
an agate mortar by grinding the solids together at room temperature
in 6 ꢀ 18 min. The structures of the products were characterized by IR,
1H NMR, MS and Elemental analysis.
Scheme.
EXPERIMENTAL
Melting points were determined with a Kofler micro melting point
apparatus and were uncorrected. IR spectra were recorded on a SP3-300
1
spectrophotometer in KBr. H NMR spectra were measured on a FT-80A
spectrometer using TMS as internal standard and (CD3)2CO as solvent.
Elemental analyses were performed on a Carlo-Erba 1102elemental
analyzer. Mass spectra were obtained on a KRATOS-AEI-MS50.
General procedure: A mixture of aryl isothiocyanate 1 (1 mmol)
and acylhydrazine 2 (1 mmol) was ground thoroughly in an agate mortar.
The mixture began to soften and melt in 1 ꢀ 2minutes. Grinding was con-
tinued until the mixture became into solid again. The reaction was moni-
tored by TLC. When the reaction was completed (6 ꢀ 18 min), the crude
products was recrystallized from ethanol. Dryness in vacuo gave the pure
products.

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1795
Table. Solid-State Preparation of Acyl Thiosemicarbazides
Reaction Time
(min)
m.p.
(ꢂC)
Yield
(%)
Product
X
Ar
C6H5
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
Cl
Br
EtO
Cl
Br
EtO
Cl
Br
EtO
Cl
7
10
6
9
8
11
8
7
18
16
17
188 ꢀ 190
183.5 ꢀ 184.5
181 ꢀ 183
89.1
86.5
91.0
87.2
88.7
84.7
85.0
90.7
90.3
86.9
84.5
C6H5
3-Cl C6H4
3-Cl C6H4
3-Cl C6H4
1-C10H7CH2
1-C10H7CH2
1-C10H7CH2
C6H5OCH2
C6H5OCH2
186.5 ꢀ 187.5
190 ꢀ 191
174 ꢀ 176
174.5 ꢀ 176
180 ꢀ 181
177 ꢀ 179
3j
3k
181 ꢀ 183
Br
188.5 ꢀ 190
All the compounds gave satisfactory analytical and spectral data:
1-Benzoyl-4-p-chlorophenyl thiosemicarbazide 3a: IR (KBr)/cmꢁ1
:
1
3357, 3187, 3031, 1673, 1600, 1509, 1400, 1255, 833, 779, 690; H NMR
d: 7.29 ꢀ 8.00 (m, 9H, ArH), 8.94 (s, 1H, NH), 9.60 (s, 1H, NH), 9.84 (s, 1H,
NH); Anal. Calcd. for C14H12ClN3OS: C, 54.99; H, 3.93; N, 13.75. Found:
C, 54.78; H, 3.61; N, 13.57.
1-Benzoyl-4-p-bromophenyl thiosemicarbazide 3b: IR (KBr)/cmꢁ1
:
1
3312, 3271, 3210, 3030, 1668, 1634, 1578, 1221, 825, 711, 687; H NMR
d: 7.45 ꢀ 8.00 (m, 9H, ArH), 8.97 (s, 1H, NH), 9.60 (s, 1H, NH), 9.85 (s, 1H,
NH); Anal. Calcd. for C14H12BrN3OS: C, 48.00; H, 3.43; N, 12.00. Found:
C, 48.31; H, 3.61; N, 11.89. MS (m/z): 351(Mþ), 215, 213, 173, 171, 145,
134(B), 105, 77.
1-Benzoyl-4-p-ethoxyphenyl thiosemicarbazide 3c: IR (KBr)/cmꢁ1: 3320,
3276, 3200, 3035, 1670, 1635, 1590, 1545, 1230, 830, 770, 685; 1H NMR d: 1.34
(t, 3H, CH3), 4.01 (q, 2H, CH2), 6.83 ꢀ 8.01 (m, 9H, ArH), 8.74 (s, 1H, NH),
9.37 (s, 1H, NH), 9.79 (s, 1H, NH); Anal. Calcd. for C16H17N3O2S: C, 60.95;
H, 5.40; N, 13.33. Found: C, 60.69; H, 5.61; N, 13.37.
1-m-Chlorobenzoyl-4-p-chlorophenyl thiosemicarbazide 3d: IR (KBr)/
cmꢁ1: 3318, 3215, 3153, 3033, 1671, 1638, 1620, 1546, 1209, 822, 735, 673;
1H NMR d: 7.32 ꢀ 7.99 (m, 8H, ArH), 8.98 (s, 1H, NH), 9.61 (s, 1H, NH),
9.96 (s, 1H, NH); Anal. Calcd. for C14H11Cl2N3OS: C, 49.41; H, 3.24; N,
12.35. Found: C, 49.78; H, 3.61; N, 12.67. MS (m/z): 341(Mþ), 171, 169(B),
139, 137, 111, 75.
1-m-Chlorobenzoyl-4-p-bromophenyl thiosemicarbazide 3e: IR (KBr)/
cmꢁ1: 3317, 3213, 3151, 3075, 1671, 1638, 1622, 1546, 1211, 819, 770, 673;
1H NMR d: 7.46 ꢀ 7.98 (m, 8H, ArH), 8.99 (s, 1H, NH), 9.61 (s, 1H, NH),

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LI ET AL.
9.97 (s, 1H, NH); Anal. Calcd. for C14H11BrClN3OS: C, 43.69; H, 2.86; N,
10.92. Found: C, 43.78; H, 2.61; N, 10.77.
1-m-Chlorobenzoyl-4-p-ethoxyphenyl thiosemicarbazide 3f: IR (KBr)/
cmꢁ1: 3318, 3220, 3150, 3030, 2980, 2920, 1670, 1640, 1620, 1550, 1215,
825, 770, 680; 1H NMR d: 1.32(t, 3H, CH 3), 4.01 (q, 2H, CH2),
6.83 ꢀ 7.99 (m, 8H, ArH), 8.77 (s, 1H, NH), 9.39 (s, 1H, NH), 9.92(s,
1H, NH); Anal. Calcd. for C16H16ClN3O2S: C, 54.94; H, 4.58; N, 12.02.
Found: C, 54.69; H, 4.61; N, 12.37.
1-(1-Naphthoacetyl)-4-p-chlorophenyl thiosemicarbazide 3g: IR (KBr)/
cmꢁ1: 3316, 3290, 3213, 3035, 1681, 1652, 1619, 1542, 1210, 832, 785;
1H NMR d: 4.13 (s, 2H, CH2), 7.30 ꢀ 8.15 (m, 11H, ArH), 8.91 (s, 1H,
NH), 9.20 (s, 1H, NH), 9.40 (s, 1H, NH); Anal. Calcd. for
C19H16ClN3OS: C, 61.71; H, 4.33; N, 11.37. Found: C, 61.31; H, 4.31; N,
11.59.
1-(1-Naphthoacetyl)-4-p-bromophenyl thiosemicarbazide 3h: IR (KBr)/
cmꢁ1: 3315, 3287, 3210, 3034, 1680, 1650, 1620, 1545, 1213, 820, 769, 675;
1H NMR d: 4.13 (s, 2H, CH2), 7.45 ꢀ 8.15 (m, 11H, ArH), 8.94 (s, 1H, NH),
9.21 (s, 1H, NH), 9.46 (s, 1H, NH); Anal. Calcd. for C19H16BrN3OS: C,
55.07; H, 3.89; N, 10.14. Found: C, 55.31; H, 4.01; N, 10.29.
1-(1-Naphthoacetyl)-4-p-ethoxyphenyl thiosemicarbazide 3i: IR (KBr)/
cmꢁ1: 3272, 3190, 3046, 3013, 2981, 2929, 1670, 1654, 1600, 1538, 1243, 820,
1
782; H NMR d: 1.34 (t, 3H, CH3), 4.01 (q, 2H, CH2), 4.13 (s, 2H, CH2),
6.82 ꢀ 8.17 (m, 11H, ArH), 8.70 (s, 1H, NH), 8.99 (s, 1H, NH), 9.41 (s, 1H,
NH); Anal. Calcd. for C21H21N3O2S: C, 66.49; H, 5.54; N, 11.08. Found: C,
66.31; H, 5.50; N, 11.29; MS (m/z): 380(Mþ), 179, 150(B), 141, 115, 65.
1-p-Phenoxyacetyl-4-p-chlorophenyl thiosemicarbazide 3j: IR (KBr)/
1
cmꢁ1: 3265, 3200, 3099, 2944, 1701, 1597, 1543, 1223, 825, 756, 689; H
NMR d: 4.66 (s, 2H, CH2), 6.97 ꢀ 7.57 (m, 9H, ArH), 8.92(s, 1H, NH), 9.39
(s, 1H, NH), 9.74 (s, 1H, NH); Anal. Calcd. for C15H14ClN3O2S: C, 53.65;
H, 4.17; N, 12.52. Found: C, 53.31; H, 4.50; N, 12.09; MS (m/z): 335(Mþ),
171, 169(B), 127, 111, 94, 77, 75.
1-p-Phenoxyacetyl-4-p-bromophenyl thiosemicarbazide 3k: IR (KBr)/
cmꢁ1: 3264, 3210, 3094, 2998, 2941, 1701, 1596, 1543, 1222, 836, 756, 689;
1H NMR d: 4.65 (s, 2H, CH2), 6.97 ꢀ 7.50 (m, 9H, ArH), 8.92(s, 1H, NH),
9.39 (s, 1H, NH), 9.75 (s, 1H, NH); Anal. Calcd. for C15H14BrN3O2S: C,
47.37; H, 3.68; N, 11.05. Found: C, 47.31; H, 3.50; N, 11.39.
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Received in the UK July 14, 2000

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