A new and efficient solid state synthesis of diaryl thioureas

Article abstract of DOI:10.1081/SCC-100103270

Fourteen diaryl thioureas which are physiologically active have been synthesized in the solid state at room temperature. The reaction needs only simple equipment and gives excellent yields.

Full text of DOI:10.1081/SCC-100103270

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A NEW AND EFFICIENT SOLID
STATE SYNTHESIS OF DIARYL
THIOUREAS
Jian-Ping Li a , Yu-Lu Wang b , Hong Wang a , Qian-
Fu Luo a & Xiao-Yang Wang a
a Department of Chemistry , Henan Normal
University , Xinxiang, 453002, China
b Department of Chemistry , Henan Normal
University , Xinxiang, 453002, China
Published online: 16 Aug 2006.
To cite this article: Jian-Ping Li , Yu-Lu Wang , Hong Wang , Qian-Fu Luo & Xiao-
Yang Wang (2001) A NEW AND EFFICIENT SOLID STATE SYNTHESIS OF DIARYL
THIOUREAS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:5, 781-785, DOI: 10.1081/
SCC-100103270
To link to this article: http://dx.doi.org/10.1081/SCC-100103270
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SYNTHETIC COMMUNICATIONS, 31(5), 781–785 (2001)
A NEW AND EFFICIENT SOLID STATE
SYNTHESIS OF DIARYL THIOUREAS
Jian-Ping Li, Yu-Lu Wang,* Hong Wang, Qian-Fu Luo,
and Xiao-Yang Wang
Department of Chemistry, Henan Normal University
Xinxiang, 453002, China
ABSTRACT
Fourteen diaryl thioureas which are physiologically
active have been synthesized in the solid state at room tem-
perature. The reaction needs only simple equipment and gives
excellent yields.
In recent years, particularly intense interest has been directed towards
the generation of small organic molecules by solid state reactions.1 These
reactions are especially appealing because they have such advantages as high
efficiency and selectivity,2 easy separation and purification, mild reaction
conditions,3 and environmental acceptability.4,5 This approach has been
widely used in a variety of organic reactions including substitution,6
condensation,7 oxidation-reduction,8,9 rearrangement10 and elimination.11
However, the solid state addition to thiocyanates of aromatic primary
amines has not been reported.
Recently, we found that the addition of thiocyanates and aromatic
primary amine to form diaryl thioureas can easily be achieved in the
solid state.
* Corresponding author. E-mail: hnsdyj@public.xxptt.ha.cn
781
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

782
LI ET AL.
N,N0-Disubstituted thioureas are known to exhibit antiviral,12
antituberculous,13 fungicidal,14 and herbicidal15 activities. Generally, the
preparation of these compounds has been carried out in solution.
In this paper, a new solid state addition of thiocyanates and aromatic
primary amine is studied and fourteen diaryl thioureas have been synthe-
sized in excellent yields at room temperature. This method requires only
simple equipment and short reaction time. The structures of the products
1
were confirmed by IR and H NMR spectroscopy, and by elemental analy-
sis.
Scheme 1.
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 Bruker
DPX-400M spectrometer using TMS as internal standard and CDCl3 as
solvent. Elemental analyses were performed on PE-2400 CHN elemental
analyser.
General Procedure
A mixture of aryl isothiocyanate16 (1 mmol) and aromatic primary
amine (1 mmol) was ground thoroughly in an agate mortar. The reaction
was traced with thin-layer chromatography. After the reaction was complete

DIARYL THIOUREAS
783
(5ꢀ40 min), the crude products were recrystallized with ethanol or acetone,
and dried under vacuum to yield the pure products.
2a: white–tabular; Yield: 95.2%; m.p. 174–176ꢁC; IR (KBr)ꢀ: 3210,
1
3030, 2985, 2850, 1595, 1490, 1250, 830 cmꢂ1; H NMR (CDCl3) ꢁ: 2.367
(s, 3H, CH3), 7.20lꢀ7.367 (m, 8H, Ar–H), 7.791(s, 1H, NH), 8.098(s, 1H,
NH); Calcd. for C14H13N2SCl: C, 60.76; H, 4.70; N, 10.13. Found: C, 60.51;
H, 4.45; N, 9.96.
2b: white–tabular; Yield: 98.0%; m.p. 176–178ꢁC; IR (KBr)ꢀ: 3215,
1
3030, 2990, 2850, 1600, 1500, 1350, 1250, 840 cmꢂ1; H NMR (CDCl3) ꢁ:
3.828 (s, 3H, CH3), 6.937ꢀ7.373 (m, 8H, Ar–H), 7.592 (s, 1H, NH), 7.877
(s, 1H, NH); Calcd. for C14H13N2SClO: C, 57.44; H, 4.44; N, 9.57. Found:
C, 57.31; H, 4.25; N, 9.30.
2c: white–needle; Yield: 97.7%; m.p. 188–190ꢁC; IR (KBr)ꢀ: 3220,
1
3030, 1595,1500, 1235, 820, 780 cmꢂ1; H NMR (CDCl3) ꢁ: 7.261ꢀ7.961
(m, 11H, Ar–H), 8.052–8.072 (d, 2H, NH); Calcd. for C17H13N2SCl: C,
65.28; H, 4.16; N, 8.96. Found: C, 65.12; H, 3.89; N, 8.67.
2d: white–stick; Yield: 90.4%; m.p. 174–176ꢁC; IR (KBr)ꢀ: 3220, 3180,
1
3030, 1590, 1550, 1490, 1245, 820 cmꢂ1; H NMR (CDCl3) ꢁ: 7.303ꢀ7.402
(m, 8H, Ar–H), 7.815 (s, 2H, NH); Calcd. for C13H10N2SCl2: C, 52.70; H,
3.38; N, 9.46. Found: C, 52.45; H, 3.02; N, 9.09.
2e: white–stick; Yield: 92.1%; m.p.179–181ꢁC; IR (KBr)ꢀ: 3210, 3030,
1595, 1495, 1235, 830 cmꢂ1; 1H NMR (CDCl3) ꢁ: 7.261ꢀ7.553 (m, 8H, Ar–
H), 7.728ꢀ7.742 (d, 2H, NH); Calcd. for C13H10N2SBrCl: C, 45.81; H, 2.94;
N, 8.22. Found: C, 45.50; H, 2.72; N, 7.97.
2f: pale–red–stick; Yield: 91.9%; m.p. 180–182ꢁC; IR (KBr)ꢀ: 3220,
3030, 1600, 1500, 1240, 825 cmꢂ1; 1H NMR (CDCl3) ꢁ: 7.255ꢀ7.546 (m, 8H,
Ar–H), 7.723ꢀ7.438 (d, 2H, NH); Calcd. for C13H10N2SClI: C, 40.26; H,
2.58; N, 7.23. Found: C, 40.01; H, 2.33; N, 6.95.
2g: white–tabular; Yield: 97.0%; m.p. 180–182ꢁC; IR (KBr)ꢀ: 3220,
1
3030, 2990, 2850, 1600, 1495, 1350, 1245, 835 cmꢂ1; H NMR (CDCl3)
ꢁ: 2.372 (s, 3H, CH3), 7.210ꢀ7.376 (m, 8H, Ar–H), 7.801 (s, 1H, NH),
8.120 (s, 1H, NH); Calcd. for C14H13N2SBr: C, 52.34; H, 4.05; N, 8.72.
Found: C, 52.14; H, 3.76; N, 8.41.
2h: white–tabular; Yield: 93.7%; m.p. 182–184ꢁC; IR (KBr)ꢀ: 3215,
1
3030, 2985, 2850, 1595, 1550, 1350, 1250, 840 cmꢂ1; H NMR (CDCl3)
ꢁ: 3.821(s, 3H, CH3), 6.940ꢀ7.541 (m, 8H, Ar–H), 7.546 (s, 1H, NH),
7.841 (s, 1H, NH); Calcd. for C14H13N2SBrO: C, 49.85; H, 3.86; N, 8.31.
Found: C, 49.72; H, 3.57; N, 8.02.
2i: white–needle; Yield: 92.9%; m.p. 182–183ꢁC; IR (KBr)ꢀ: 3220,
1
3030, 1595, 1495, 1235, 820, 780 cmꢂ1; H NMR (CDCl3) ꢁ: 7.267–7.968
(m, 11H, Ar–H), 8.060ꢀ8.079 (d, 2H, NH); Calcd. for C17H13N2SBr: C,
57.14; H, 3.64; N, 7.84. Found: C, 56.84; H, 3.47; N, 7.56.

784
LI ET AL.
2j: white–tabular; Yield: 92.2%; m.p. 188–190ꢁC; IR (KBr)ꢀ: 3220,
1
3180, 3030, 1600, 1500, 1245, 825 cmꢂ1; H NMR (CDCl3) ꢁ: 7.290ꢀ7.392
(m, 8H, Ar–H), 7.820 (s, 2H, NH); Calcd. for C13H10N2SBr2: C, 40.41; H,
2.59; N, 7.25. Found: C, 40.19; H, 2.31; N, 6.98.
2k: white–tabular; Yield: 89.5%; m.p. 179–181ꢁC; IR (KBr)ꢀ: 3225,
3030, 1595, 1495, 1240, 820 cmꢂ1; 1H NMR (CDCl3) ꢁ: 7.251ꢀ7.541 (m, 8H,
Ar–H), 7.720ꢀ7.433 (d, 2H, NH); Calcd. for C13H10N2SBrI: C, 36.03; H,
2.31; N, 6.47. Found: C, 35.74; H, 2.02; N, 6.19.
2l: white–tabular; Yield: 92.3%; m.p. 138–140ꢁC; IR (KBr)ꢀ: 3210,
3030, 2995, 2930, 2890, 1600, 1530, 1400, 1250, 835 cmꢂ1 1H NMR
;
(CDCl3) ꢁ: 1.420 (t, 3H, CH3), 2.362 (s, 3H, CH3), 4.040 (q, 2H, CH2),
6.910–7.690 (m, 8H, Ar–H), 7.640ꢀ7.643 (d, 2H, NH); Calcd. for
C16H18N2SO: C, 67.13; H, 6.29; N, 9.79. Found: C, 66.81; H, 5.92; N, 9.53.
2m: white–tabular; Yield: 90.5%; m.p. 159–160ꢁC; IR (KBr)ꢀ: 3215
1
3030, 2995, 2895, 1600, 1500, 1355, 1250, 840 cmꢂ1; H NMR (CDCl3) ꢁ:
1.417 (t, 3H, CH3), 3.814 (s, 3H, CH3), 4.032 (q, 2H, CH2) 6.902ꢀ7.631 (m,
8H, Ar–H), 7.634ꢀ7.637 (d, 2H, NH); Calcd. for C16H18N2SO2: C, 63.58;
H, 5.96; N, 9.27. Found: C, 63.29; H, 5.60; N, 8.99.
2n: white–needle; Yield: 96.8%; m.p. 178–179ꢁC; IR (KBr)ꢀ: 3220,
3030, 2995, 2890, 1595, 1500, 1400, 1355, 825, 785 cmꢂ1 1H NMR
;
(CDCl3) ꢁ: 1.397(t, 3H, CH3), 4.009 (q, 2H, CH2), 6.871–8.002 (m, 1H,
Ar–H), 8.003ꢀ8.014 (d, 2H, NH); Calcd. for C19H18N2SO: C, 70.81; H,
5.59; N, 8.70. Found: C, 70.58; H, 5.33; N, 8.35.
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Received in the U.K. February 7, 2000