Synthesis of benzoyl-N-phenylthioureas under microwave irradiation and phase transfer catalysis conditions

Article abstract of DOI:10.1081/SCC-120001519

A simple, rapid and efficient method for the synthesis of benzoyl-N-phenylthioureas under microwave irradiation is reported. The effect of microwave irradiation power, times and phase transfer catalyst on the reaction is investigated.

Full text of DOI:10.1081/SCC-120001519

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SYNTHESIS OF BENZOYL-N-PHENYLTHIOUREAS UNDER
MICROWAVE IRRADIATION AND PHASE TRANSFER
CATALYSIS CONDITIONS
Lin Bai a b , Shengying Li b , Jin-Xian Wang & Mingkai Chen b
a Department of Chemistry, Northwest Normal University, Lanzhou, 730070, P. R. China
b Department of Chemistry, Lanzhou Teachers College, Lanzhou, 730070, P. R. China
Published online: 21 Aug 2006.
To cite this article: Lin Bai , Shengying Li , Jin-Xian Wang & Mingkai Chen (2002) SYNTHESIS OF BENZOYL-N-
PHENYLTHIOUREAS UNDER MICROWAVE IRRADIATION AND PHASE TRANSFER CATALYSIS CONDITIONS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:1, 127-132, DOI:
10.1081/SCC-120001519
To link to this article: http://dx.doi.org/10.1081/SCC-120001519
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SYNTHETIC COMMUNICATIONS, 32(1), 127–132 (2002)
SYNTHESIS OF BENZOYL-N-
PHENYLTHIOUREAS UNDER
MICROWAVE IRRADIATION AND
PHASE TRANSFER
CATALYSIS CONDITIONS
Lin Bai,1,2 Shengying Li,2 Jin-Xian Wang,1,
*
and Mingkai Chen2
1Department of Chemistry, Northwest Normal
University, Lanzhou, 730070, P. R. China
2Department of Chemistry, Lanzhou Teachers
College, Lanzhou, 730070, P. R. China
ABSTRACT
A simple, rapid and efficient method for the synthesis of
benzoyl-N-phenylthioureas under microwave irradiation is
reported. The effect of microwave irradiation power, times
and phase transfer catalyst on the reaction is investigated.
Many methods have been described for the preparation of both acyl
and aroyl isothiocyanates,1–7 which are important for the synthesis of acyl
phenylthioureas. The reaction of acyl chloride with thiocyanate under phase
transfer catalysis is a good method for the preparation of acyl isothio-
cyanates,1,6,7 which react with aniline to afford the acyl phenylthioureas.1,2
*Corresponding author.
127
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128
BAI ET AL.
The applications of ultrasound in organic synthesis have been rapidly
developed. Li and coworkers8 have shown that phenylacetyl arylthioureas
can be obtained from the corresponding acyl chlorides under ultrasound
condition. Using polyethylene glycol-400 as phase transfer catalyst the
phenylacetyl arylthioureas can produce high yield, but the reaction requires
long time.
Microwave heating has been used for a wide variety of applications
including the rapid synthesis of organic compounds and some important
reviews have been published.9 There are a variety of methods for carrying
out microwave assisted organic reactions using domestic or commercial
ovens. We have reported the use of this technology in the synthesis of the
substituted glycerol selenide ethers,10 diaryl diselenides,11 chiral glycerol
sulfide ethers12 and 8-quinolinyl ethers.13
Recently, we have found that benzoy phenylthioureas 4 can be
obtained from the reaction of substituted benzoyl chloride 1 with first
ammonium thiocyanate and then aniline 3 in a two-phase system, at poly-
ethylene glycol-400 as the catalyst under microwave irradiation condition.
This method is very simple, rapid and affords good yields of benzoyl-N-
phenylthioureas. The reactions are shown in the Scheme and the results for
the compounds prepared are listed in Table 1. All products were charac-
1
terized by H NMRand IRspectra.
Scheme.
RESULTS AND DISCUSSION
Using the reaction of benzoyl chloride with NH4SCN and C6H5NH2
as an example, we investigated the effect of the power and time of

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SYNTHESIS OF BENZOYL-N-PHENYLTHIOUREAS
Table 1. Benzoyl-N-phenyl Thioureas 4a–j Prepareda
129
Entry
Product
M.P./ꢀC Lit. M.P./ꢀC Yield/%
3a
3b
3c
3d
3e
3f
3g
3h
3i
C6H5CONHCSNHC6H5
135.8
153.2
112.6
132.5
84.4
125.8
163.6
108.4
154.7
149.3
1361
92
85
86
84
80
72
85
93
66
65
2-ClC6H4CONHCSNHC6H5
3-CH3C6H4CONHCSNHC6H5
4-CH3C6H4CONHCSNHC6H5
4-OCH3C6H4CONHCSNHC6H5
3,5-(OCH3)2C6H3CONHCSNHC6H5
C6H5CH¼CHCONHCSNHC6H5
C6H5CH2CONHCSNHC6H5
a-C10H7CONHCSNHC6H5
b-C10H7CONHCSNHC6H5
1531
1131
132–1333
841
125.53
163,1 163–1643
107–1083
1543
3j
148,1 148.53
aTime/Power: 14 min, 750 W.
microwave irradiation on the reaction. The results are summarized in Table 2
and Table 3. The result shown that the highest yield for compounds 4 can be
obtained at 750 W power with 14 min reaction time under microwave
irradiation conditions.
The use of phase transfer catalysis for nucleophilic substitution reac-
tion is well documented.14,15 The mechanism of synthesis of benzoyl
isothiocyanate under phase transfer catalysis has been discussed.7 We
studied the effect of different phase transfer catalyst on the reaction. It
was found that the activities of the catalysts are in the following sequence:
PEG-400>PEG-600>Bu4NBr>C6H5CH2N(CH3)3Cl>Bu4NI. The results
shown in Table 4.
The heating effect utilized in microwave assisted organic transforma-
tions is due to the dielectric constant of solvent. The larger the dielectric
constant, the greater the coupling with microwaves.10–13 We found when
power at 750 W, a reaction time of 14 min and using CHCl3 which has
large dielectric constant and high boiling point, as solvent, the yield of
the one-step transformation of compound 1 to benzoyl phenylthiourea 4 is
very good.
The quantity of dimethylformamide is very important in the reaction.
When a small amount of dimethylformamide is added to the hetero-
geneous reaction mixture, rapid reaction occurs between dimethylformamide
and NH4SCN to produce dimethylformamide ammonium ion pairs,
ðCH3Þ2NCHOÀNHþ4 , which is distributed into the chloroform layer. Which
eventually facilitates the nuoleophilic displacement reaction.15 Experiment
results showed that 2 drops dimethylformamide was added into the
heterogeneous mixture, the efficiency were very good. In the absence of

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BAI ET AL.
Table 2. Effect of the Time of Microwave Irradiation
on the Formation of Benzoyl Isothiocyanate 2a and
Benzoyl-N-phenyl Thiourea 4aa,b
Synthesis
of 2a (min)
Synthesis
of 4a (min)
Yieldc
(%)
Entry
1
2
3
4
5
6
7
8
9
10
9
10
11
12
8
3
3
3
3
4
4
4
5
4
6
78
80
82
84
83
87
92
90
91
88
9
10
10
11
10
aMolar ratio: C6H5COCl : NH4SCN : p-ClC6H4NH2 :
PEG-400 ¼ 1.2 : 1 : 1.8 : 0.1.
bThe power of microwave irradiation is 750 W.
cIsolated yield of the one-step transformation of com-
pound 1a to 4a.
Table 3. Effect of the Power of Microwave Irradiation on the Formation of
Benzoyl-N-phenyl Thiourea 4aa,b
Power (W)
Yield (%)c
375
80
525
82
600
86
675
90
750
92
800
90
850
87
aMolar ratio: C6H5COCl : NH4SCN : C6N5NH2 : PEG-400 ¼ 1.2 : 1 : 1.8 : 0.1.
bThe time of microwave irradiation is 14 min.
cYield of isolated product.
Table 4. Effect of the Phase Transfer Catalyst on the Formation of Benzoyl-
N-phenyl Thiourea 4aa,b
Power (W)
Yield (%)c
PEG-400
92
PEG-600
87
Bu4NBr
84
Bu4NI
76
C6H5CH2N(CH3)3Cl
80
aMolar ratio: C6H5COCl : NH4SCN : C6H5NH2 : PEG-400 ¼ 1.2 : 1 : 1.8 : 0.1.
bTime/Power: 14 min, 750 W.
cYield of isolated product.

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SYNTHESIS OF BENZOYL-N-PHENYLTHIOUREAS
131
dimethylformamide the reaction of C6H5COCl with SCNÀ will require
long time.
EXPERIMENTAL
The melting points were determined on a WRS-1A digital melting
point apparatus. IRspectra were measured for KBr discs using an Alpha
Centauri FT-IRspectrophotometer. 1H NMRspectra (80 MHz) were
recorded in CDCl3 using a FT-80 spectrometer. J values are given in Hz.
Microwave irradiation is carried out with an improved reflux Galanz WP
750B commercial microwave oven at 2450 MHz.
General Procedure
In a typical experiment, the ammonium thiocyanate (4.5 mmol),
benzoyl chloride (3 mmol), PEG-400 (0.25 mmol), DMF (2 drops) and
trichloromethane (20 mL) were added in a bottle (50 mL), and refluxed
under microwave irradiation at 750 W for 10 min. Then a mixture of aniline
(2.5 mmol) and trichloromethane (5 mL) was added dropwise over a period of
2 min and irradiated continued for 2 min. After cooling to room temperature
and water (15 mL) was added. The organic layer was separated, the aqueous
phase was washed with trichloromethane (2 ꢁ 5 mL). The combined
trichloromethane layer was dried over anhydrous MgSO4. The solvent was
removed by evaporation under reduced pressure to afford the benzoyl-N-
phenylthiourea 4. Recrystallization from ethanol gave the analytically pure
product.
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Received in the Netherlands February 28, 2001

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