Phase transfer catalytic synthesis of phenylacetyl arylthioureas under microwave irradiation conditions

Article abstract of DOI:10.1081/SCC-120003147

A simple, rapid, and efficient method for the synthesis of phenylacetyl arylthioureas under microwave irradiation is reported. The effects of microwave irradiation power, times, and solvent on the reaction are investigated.

Full text of DOI:10.1081/SCC-120003147

This article was downloaded by: [California Institute of Technology]
On: 05 October 2014, At: 06:10
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
PHASE TRANSFER CATALYTIC SYNTHESIS OF
PHENYLACETYL ARYLTHIOUREAS UNDER MICROWAVE
IRRADIATION CONDITIONS
Lin Bai a b , Kanglan Li b , Shengying Li b & Jin-Xian Wang a
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 , Kanglan Li , Shengying Li & Jin-Xian Wang (2002) PHASE TRANSFER CATALYTIC SYNTHESIS OF
PHENYLACETYL ARYLTHIOUREAS UNDER MICROWAVE IRRADIATION CONDITIONS, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:7, 1001-1007, DOI: 10.1081/SCC-120003147
To link to this article: http://dx.doi.org/10.1081/SCC-120003147
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 32(7), 1001–1007 (2002)
PHASE TRANSFER CATALYTIC
SYNTHESIS OF PHENYLACETYL
ARYLTHIOUREAS UNDER MICROWAVE
IRRADIATION CONDITIONS
Lin Bai,1,2 Kanglan Li,2 Shengying Li,2
and Jin-Xian Wang1,
*
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
phenylacetyl arylthioureas under microwave irradiation is
reported. The effects of microwave irradiation power, times,
and solvent on the reaction are investigated.
Acyl isothiocyanates have been known as important intermediates in
organic synthesis for a long time.1 Many methods have been described for
the synthesis of both acyl and aroyl isothiocyanates.2–7 However, long reac-
tion times, expensive reagents and anhydrous conditions are often required
for their preparation.2 Reeves and coworkers4,7 were the first to use phase
transfer catalysis to prepare acyl isothiocyanates. They offered an attractive
*Corresponding author.
1001
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1002
BAI ET AL.
alternative for the preparation of both acyl and aroyl isothiocyanates.
However, toxic potassium thiocyanate is part of the waste and the product
obtained is low in yield. Recently Wei and Chen8 improved Reeves’ method,
providing shorter reaction times, simple operation, and high yield. The
isothiocyanates were converted to the acyl-N-phenylthioureas by treating
with aniline for the purpose of characterization.2,4
The application of ultrasound in organic synthesis has been rapidly
developed. Li and coworkers9 have shown that phenylacetyl arylthioureas
can be obtained from the corresponding acyl chlorides under ultrasound
conditions. Using polyethylene glycol-400 as the phase transfer catalyst,
the phenylacetyl arylthioureas can be obtained in high yield, but the reaction
requires a 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.10 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
substituted glycerol selenide ethers,11,12 chiral glycerol sulfide ethers13, and
8-quinolinyl ethers.14
Recently, we have found that phenylacetyl arylthioureas 4 can be
obtained from the reaction of phenylacetyl chloride 1 with first ammonium
thiocyanate and then arylamines 3 in a solid–liquid system with poly-
ethylene glycol-400 as a catalyst under microwave irradiation. This
method is very simple, rapid, and affords good yields of phenylacetyl
arylthioureas. The reactions are shown in the scheme and the results for
the compounds prepared are listed in Table 1.
Scheme.

PHENYLACETYL ARYLTHIOUREAS
1003
Table 1. Phenylacetyl Arylthioureas 4a–j Prepareda
M.P. (ꢀC) Lit. M.P. (ꢀC)9 Yield (%)
Entry
Product
4a
157.7
116.3
175.2
145.2
142.4
170.5
153.2
124.6
157.7
169.4
155–156
116–117
174–175
146–147
141.5–142.5
171
94
76
87
88
83
91
62
77
67
86
4b
4c
4d
4e
4f
4g
4h
4i
151.5–152.5
124
156–157
168.5–169
4j
aTime/Power: 14 min, 750 W.
RESULTS AND DISCUSSION
Using the reaction of phenylacetyl chloride with NH4SCN and
p-ClC6H4NH2 as an example, we investigated the effect of the power and
time of microwave irradiation on the reaction. The results are summarized
in Tables 2 and 3. The results show that the highest yield for compounds 4
can be obtained at 750 W with 14 min reaction time under microwave
irradiation conditions.
The efficiency of various solvents on the formation of N-phenylacetyl-
N0-4-chloro-arylthiourea 4a was studied using PEG-400 as a phase transfer
catalyst under microwave irradiation at 750 W for 14 min. CHCl3 was found
to be an effective solvent for the reaction. The effects of various solvents
in the synthesis of N-phenylacetyl-N0-4-chloroarylthiourea 4a are shown in
Table 4.
The use of phase transfer catalysis for nucleophilic substitution reac-
tions is well documented.15,16 The mechanism of the synthesis of benzoyl

1004
BAI ET AL.
Table 2. Effect of the Power of Microwave Irradiation on the Formation of
N-Phenylacetyl-N0-4-chloro-arylthiourea 4aa,b
Power (W)
Yield (%)c
375
85
525
89
600
91
675
93
750
94
800
92
850
88
aMolar ratio: PhCH2COCl : NH4SCN : p-ClC6H4NH2 : PEG-400 ¼ 1.2 : 1 : 1.8 : 0.1.
bThe time of microwave irradiation is 14 min.
cYield of isolated product.
Table 3. Effect of the Time of Microwave Irradiation on
the Formation of Phenylacetyl-Isothiocyanate
2 and
N-Phenylacetyl-N0-4-chloro-arylthiourea 4aa,b
Synthesis of 2
(min)
Synthesis of 4a
(min)
Yieldc
(%)
Entry
1
2
3
4
5
6
7
8
9
9
10
11
12
9
10
10
11
10
3
3
3
3
4
4
5
4
6
87
89
88
86
92
94
93
93
92
aMolar ratio: PhCH2COCl : NH4SCN : p-ClC6H4NH2 :
PEG-400 ¼ 1.2 : 1 : 1.8 : 0.1.
bThe time of microwave irradiation is 750 W.
cIsolated yield of the one-step transformation of compound
1 to 4a.
Table 4. Effect of Solvents on the Synthesis of N-Phenylacetyl-
N0-4-chloroarylthiourea 4a
Solvents
C6H6
CH2Cl2
CHCl3
ꢀ
Dielectric constant (e20 C
b.p. (ꢀC)
)
2.29
80.1
0
10.4
40.2
78
4.70
61.2
94
Yield (%)

PHENYLACETYL ARYLTHIOUREAS
1005
Table 5. Compare with Microwave Irradiation and Other
Methods for Phenylacetyl Arylthioureas 4a Preparation
Experimental
Conditions
Time
Yield (%)
MW-PTC
PTC9
Ultrasound-PTC9
750 W
10–30ꢀC
10–30ꢀC
14 min
2–6 h
1.5 h
94
92
95
isothiocyanate under phase transfer catalysis has been discussed. The heat-
ing effect utilized in microwave assisted organic transformation is due to the
dielectric constant of solvent. The larger the dielectric constant, the greater
the coupling with microwaves.12,13,17 We found that with the microwave
power at 750 W, a reaction time of 14 min and using CHCl3 as solvent,
which has large dielectric constant and high boiling point, the yield of the
one-step transformation of compound 1 to phenylacetyl arylthiourea 4 is
very good.
Dimethylformamide can dissolve many organic substrates and
inorganic salts. When a small amount of DMF is added to the hetero-
geneous reaction mixture, rapid reaction occurs between DMF and
NH4SCN to produce the dimethylformamide ammonium ion pairs,
ðCH3Þ2NCHOÀNHþ4 , which is distributed into the chloroform layer and
eventually facilitates the nucleophilic displacement reactions.18
The quantity of DMF in the reaction mixture is very important.
Experimental results showed that with two drops of DMF in the hetero-
geneous mixture, the efficiency was very good. In the absence of DMF the
reaction of PhCH2COCl with SCNÀ will not occur.
Compared with other methods for the synthesis of phenylacetyl
arylthioureas, using microwave irradiation conditions has the advantages
of short reaction times and high product yield. Table 5 shows the results for
different reaction conditions.
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 were given in
Hz. Microwave irradiation was carried out with an improved reflux
Galanz WP 750B commercial microwave oven at 2450 MHz.

1006
BAI ET AL.
General Procedure
In a typical experiment, ammonium thiocyanate (0.34 g, 4.5 mmol),
phenylacetyl chloride (0.46 g, 3 mmol), PEG-400 (0.1 g, 0.25 mmol), DMF
(two 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 mix-
ture of substituted aniline (2.5 mmol) and trichloromethane (5 ml) was added
dropwise over a period of 2 min and irradiation continued for 2 min. After
cooling to room temperature, water (15 ml) was added. The organic layer was
separated and the aqueous phase was washed with trichloromethane
(2 Â 5 ml). The combined trichloromethane layer was dried over anhydrous
MgSO4. The solvent was removed by evaporation under reduced pressure to
afford the phenylacetyl arylthioureas 4. Recrystallization from ethanol gave
the analytically pure products.
4a: IR n (KBr): 1692, 1607, 1598, 1495, 1152, 3241. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.25–7.67 (9H, m, ArH), 9.05 (1H, s, S¼CNH), 12.31
j
(1H, s, O¼CNH).
j
4b: IR n (KBr): 1682, 1609, 1597, 1494, 1149, 3221. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.21–7.77 (9H, m, ArH), 8.80 (1H, s, S¼CNH), 12.36
j
(1H, s, O¼CNH).
4c: IRjn (KBr): 1689, 1596, 1587, 1482, 1152, 3241. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.28–7.50 (9H, m, ArH), 8.92 (1H, s, S¼CNH), 12.35
j
(1H, s, O¼CNH).
j
4d: IR n (KBr): 1687, 1598, 1497, 1148, 3234. 1H-NMR(CDCl 3): d 2.38
(3H, s, CH3), 3.75 (2H, s, CH2), 7.14–7.51 (9H, m, ArH), 9.17
(1H, s, S¼CNH), 12.27 (1H, s, O¼CNH).
j
j
4e: IR n (KBr): 1678, 1452, 1178, 3247. 1H-NMR(CDCl 3): d 2.30 (3H,
s, CH3), 3.75 (2H, s, CH2), 7.14–7.68 (9H, m, ArH), 9.51 (1H, s, S¼CNH),
j
12.02 (1H, s, O¼CNH).
j
4f: IR n (KBr): 1691, 1659, 1597, 1458, 1162, 3243. 1H-NMR(CDCl 3):
d 2.61 (3H, s, COCH3), 3.75 (2H, s, CH2), 7.28–7.40 (5H, m, ArH), 7.78–
8.04 (4H, m, ArH), 8.86 (1H, s, S¼CNH), 12.58 (1H, s, O¼CNH).
j
j
4g: IR n (KBr): 1678, 1607, 1584, 1462, 1157, 3251. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.26–8.39 (9H, m, ArH), 8.91 (1H, s, S¼CNH), 13.05
j
(1H, s, O¼CNH).
j
4h: IR n (KBr): 1688, 1587, 1486, 1456, 1174, 3197. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.28–8.69 (9H, m, ArH), 9.12 (1H, s, S¼CNH), 12.65
j
(1H, s, O¼CNH).
4i: IRjn (KBr): 1708, 1612, 1594, 1454, 1187, 3184. 1H-NMR(CDCl 3):
d 3.75 (2H, s, CH2), 7.28–7.48 (5H, m, ArH), 7.90–8.34 (4H, m, ArH), 8.72
(1H, s, S¼CNH), 12.76 (1H, s, O¼CNH).
j
j

PHENYLACETYL ARYLTHIOUREAS
1007
4j: IR n (KBr): 1689, 1600, 1456, 1175, 3198. 1H-NMR(CDCl 3): d 3.75
(2H, s, CH2), 7.22–8.01 (12H, m, ArH), 9.20 (1H, s, S¼CNH), 12.48 (1H, s,
j
O¼CNH).
j
REFERENCES
1. Dixo, A.E.; Taylor, J. J. Chem. Soc. 1908, 93, 648.
2. Smith, P.A.S.; Kan, R.O. J. Org. Chem. 1964, 29, 2261–2265.
3. Cainelli, G.; Manescalchi, F. Synthesis 1979, 141–144.
4. Reeves, W.P.; Simmons, A.Jr., et al. Synth. Commun. 1981, 11(10),
781–785.
5. Lipp, M.; Dallacker, F.; Koenen, G. Chem. Ber. 1958, 91, 1660.
6. Ivanovz, Zh.M.; Kirsanova, N.A.; Derkach, C.I. Zh. Organ. Khim.
1965, 1(12), 2186; CA, 1966, 64, 11123c.
7. Reeves, W.P.; Simmons, A., et al. Synth. Commun. 1980, 10(8), 633.
8. Taibao Wei; Jichou Chen. Pesticides (Chinese) 1995, 34(2), 12–14.
9. Li, Y.; Guo, W.; Xu, Y., et al. Chin. J. Appl. Chem. 1998, 15(1), 95–
97.
10. (a) Caddick, K. Tetrahedron 1995, 51, 10403–10432. (b) Strauss, C.R.;
Trainor, R.W. Australian J. Chem. 1995, 48, 1665–1692. (c) Galema,
S.A. Chem. Soc. Rev. 1997, 26, 233–238.
11. Wang, J.-X.; Wu, X.; Hu, Y., et al. J. Chem. Research(S) 1999, 688–
689; J. Chem. Research(M) 1999, 688–689.
12. Wang, J.-X.; Xi, Y.; Wu, X.; Hu, Y.; Du, Z. Synth. Commun. 1998,
28(24), 4916–4627.
13. Wang, J.-X.; Zhang, Y.; Huang, D.; Hu, Y. J. Chem. Res. (S) 1998,
216–217.
14. Wang, J.-X.; Zhang, M.; Hu, Y. Synth. Commun. 1998, 28(13), 2407–
2413.
15. Starks, C.M.; Liotta, C. Phase Transfer Catalysis. Academic Press:
New York, 1978.
16. Weber, W.P.; Gokel, G.W. Phase Transfer Catalysis in Organic
Synthesis. Springer Verlag: New York, 1977.
17. Wang, J.-X.; Bai, L.; Li, W., et al. Synth. Commun. 2000, 30(2), 325–
332.
18. Hongwen Hu. Organic Chemistry, 2nd Ed.; Higher Education Press:
Beijing, 1990; 545–546.
Received in the USA March 29, 2001