Indian Journal of Chemistry
Vol. 398, September 2000, pp. 700 - 702
Note
Phase transfer catalyzed synthesis of
arene-bis-aroyl thiourea derivatives
o
II
I c-o
R.....
..........o -
You-Ming Zhang, Tai-Bao Wei· & Li-Ming Gao
Department of Chemistry, Northwest Normal University,
Lanzhou, Gansu, 730 070, P R China.
Received 22 January 1999 ; accepted (revised) 5 May 2000
Reaction of arene diamines with aroyl chloride and
ammonium thiocyanate under the condition of solid-liquid phase
transfer catalysis using polyethylene-glycol-600 (PEG-600) as the
catalysi furni shes arene-bis-aroyl thiourcas 3a-1 in good to
excellent yield . The products have been characteri zed by
analytical and spectral (IR and 'H NMR) data
PEG- 600/CH:!02
N~SCN
room terrp.
•
o
II
RVC-N=e=s
2
o
s
s
0
1\
11
/I
•
R-o-C-NH-C-NH-Ar-NH-C-NH-C"l3-R
II
3
3
a
Thioureas are excellent reservoir of bioactive
substances. A number of biological actIvItIes are
associated with substituted thiourea deri vatives l . A
survey of literature reveals that some work has been
reported on 1,3-disubstituted thiourea derivatives 2. 6 ,
but not much work has been done on the preparation
and biological activity studies of arcne-bis-aroyl
thioureas. In view of these and in continuation of our
earlier work on the synthesis of' plant growth
regulators 7. 10, we now report a convenient and
efficient method for the preparation of arene-bis-aroyl
thiourea derivatives under the condition of solidliquid phase transfer catalysis using polyethylene
glycol-600 (PEG-600) as the phase transfer catalyst.
Aroyl chloride 1 obtained by the reaction of
aromatic acid with thionyl chloride was treated with
ammonium thiocyanate under the condition of solidliquid phase transfer catalysis using 3% PEG-600 as
the catalyst to give the corresponding aroyl
isothiocyanate 2 in qualitative yield. Without
separation, compound 2 was reacted with arene
diamine to give the corresponding arene-bis-aroyl
thioureas 3 in good to excellent yields (Scheme J).
Acyl isothiocyanate have been prepared under
liquid-liquid phase transfer catalysis using tetrabutyl
ammonium bromide as the catalyst. They are after
isolation treated with aniline to give the corresponding
thiourea derivatives. However in the presences of
water, hydrolysis of the acyl chloride may occur, and
+
b
c
d
RV
Ar
0--0-0-0=
0---0--00- -?-Q",C
¢
e
0=
r
g
h
k
0-.....
o
Scheme I
C",
701
NOTES
Table I mp
(0C)
Yield
3a
223-24
98
3b
170-72
3c
Compd
Physical and analytical and 'H NMR data for compounds 3a-1
Found (required) (%)
Mol. formula
(%)
IH NMR (8, ppm)
C
H
N
C 22 H IS N•0 20 2
60.79
(60.81
4 . 16
4 . 18
12.74
12.89)
12.27 (2H , s, NH x2), 11 .32 (2H,
7.51 -8.01 (14H , m, A rH)
S,
NH x2),
97
C22HI SN.0202
60.87
(60.81
4.23
4 . 18
12.85
12.89)
12.28 (2H, S, NH x2), 11.52 (2H,
7.51 -8.01 (14H, m, ArH)
S,
NH x2),
221-22
96
C2sH22 N.0202
65.91
(65.86
4.33
4 .34
10.92
10.97)
12.31 (2H , S, NH x2), 11.65 (2H,
7.51-8 .03 ( 18H, m, ArH)
S,
NHx2),
3d
219-20
97
C)OH26N.0 20 2
66.76
(66.88
4 .92
4.87
10.51
10.40)
12.36 (2H, S, NH x2), 11.62 (2H , S, NH x2),
7.53-8 .05 (16H, m, ArH), 2.36 6H , S, H]x 2)
3e
227-28
96
C22 H I6N60 602
50.41
(50 .37
3.09
3.07
16.13
16.03)
12.41 (2H , s, NH x2), 11.42 (2H,
7.58-8.73 (12H, m, ArH)
3f
193-94
86
C22 HI6N60 602
50.49
(50.37
3. 18
3.07
16.27
16.03)
12.23 (2H, S, NH x2), 11.56 (2H , s, NH x2),
7.51-8.03 (12H, m, ArH)
3g
>250
98
C2s H20N60 602
55. S3
(55 .99
3.36
3.36
14.15
14.00)
12.49 (2H, S, NH x2), 12.02 (2H,
7.80-8.79 (16H , m, ArH)
3h
>250
92
C]OH24N60 60 2
57 .53
(55.31
3.79
3.85
13 .28
13. 37)
12.47 (2H, S, NH x2), 12.81 (2H, S, NHx2),
7.58-8.72 (14H, m, ArH), 2.36 6H , S, NH]x2)
3i
196-97
90
C 1s H 1. N.O.0 2
52 .31
(52.16
3.52
3.40
13 .67
13 .52)
12.28 (2H , S, NH x2), 11.23 (2H , S, NHx2),
6.72 (2H, m, f.-C-H x2), 7.32-8.06 (8 H, m,
ArH, f] and f5-C-H)
3j
187-8 8
86
C 1sH 1. N. O. 0 2
52 .35
(52 . 16
3.46
3.40
13.41
13 .52)
12.18 (2H, S, NH x2), 11.41 (2H, S, NHx2),
6.68-6.73 (m, f.-C-H x2), 7.32-8 .06 (8 H, m,
ArH, f) and f5-C-H)
3k
236-37
96
C 2. H 1S N 4O. O.
58. 92
(58 .76
3.65
3.70
11.41
11.42)
31
217- 18
96
C26H22N40. 0 2
60 .38
(60.21
4. 16
4.28
10.57
10.8 1)
12.41 (2H, s, NH x2), 11.27 (2H , s, N Hx2),
6.72-6. 79 (2H , m, f.-C-H x2), 7.77-8.07
(12H , m, ArH , f) and f5-C-H)
12.43 (2H , S, NH x2), 11.59 (2H, S, NI-I x2),
6.73-6.77 (2H , m, f.-C-H x2), 7.53-8.06( IOH,
m, ArH , f] and f5-C-H), 2.35 (6H, s, CH]x2)
yield of the acylisothiocyanate is decreased II .
Meshkatalsadat has reported that acyl chloride reacted
with different phenylthioureas to yield N-aryl-N'acylthioureas, but long reaction times and high
temperature are required 2 • Jirman has also reported
that substituted benzoyl chloride reacted with Nacetyl-N' -phenyl thiourea in acetone at refluxing
temperature to give N-substituted benzoyl thiourea
derivatives I2- 14 , but long reaction times and the
preparation of N-acetyl thioureas are required. Other
method l S- 16 for preparation of acythioureas have also
been reported, none of them was completely
satisfactory for our purpose. Consequently, we have
conducted our reaction under the conditions of solidliquid phase transfer catalysis using PEG -600 as the
catalyst. It was found that the aroyl chloride 1 was
quantitatively converted to the con-esponding aroyl
isothiocyanate 2. This intermediate was then treated
with arene diamines to give the thiourea derivatives 3
in high yie ld (Table I).
S,
S,
NHx2),
Hx2),
We have investigated the catalytic effect of phasetransfer catalyst on the yield of 1,4-phenylene-bisbenzoy l thiourea 3a. It was found that the phase
transfer catalyst, such as PEG-600, PEG-2000 and
PEG-6000, has obvious catalytic effects. Tetra-butylammonium bromide and 18-crown-6 can also be used
as phase transfer catalyst. Other quaternary
ammonium salts tested, IS-crown-S, DB-IS-crownS,a,~ and y-cyclodextrins are not effective. The
results are summarized in Table II .
In conclusion, this is a facile and convenient
method for the synthesis of acyl thiourea derivatives
under the condition of solid-liquid phase transfer
catalysis, with the advantages of mi ld conditions,
simp le operation, short reaction times and high yield
over the reported method. The catalyst PEG-600 is
inexpensive, relatively nontoxic, highly stable and
easily available.
702
INDIAN 1. CHEM. SEC B, SEPTEMBER 2000
Experimental Section
All melting points were determined in an open
capillary tube and are uncorrected. IR spectra(KBr)
obtained were on an Alpha contauri FT-IR spectrophotometer and I H NMR spectra on a FT-80A
(80MHz) in DMSO-d6 using TMS as internal standard
(chemical shifts in 8, ppm). Elemental analysis were
performed with a PE-2400 CHN instrument.
Table II - Catalytic effect of PTC on the yield of 1,4-phenylenebisbenzoylthiourea 3a
Yield(%)
PTC
Entry
I
2
3
4
S
6
7
8
9
10
18-Crown-6
IS-Crown-S
DB-IS-Crown-S
PEG-600
PEG-2000
PEG-6000
PEG-IOOOO
a-Cyclodextrin
P-Cyclodextrin
the mixture stirred for 30 min. The corresponding
thiourea precipitated immediately which was filtered,
washed with water to remove inorganic salts dried and
recrystallized from DMF-EtOH-H 20 to give the title
compounds 3.
Acknowledgement
We wish to express our gratitude to Nature
Science Foundation of China (No. 29571023) and
Gansu Province for financial support.
References
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76
98
93
90
78
y-Cyclodextrin
Bu4NBr
88
II
PhCH 2NBu)CI
12
PhCHlNMe)CI
13
14
.PhCHlNMe)NOl
Me 4 NCI
IS
Me 4 NI
16
NoPTC
17
a. For entry 2,3,~,9,10,12,13,14,IS,16 and 17, only 1,4-benzoylaminobenzene was obtained;
b. Based on I ,4-phenylene diamine.
General procedure for preparation of arene-bisaroyl thioureas 3. Powdered ammonium thiocyanate
(15 mmole), aroyl chloride (10 mmole), PEG-600
(0.27 g, 3% with respect to ammonium thiocyanate)
and methylene dichloride (25 mL) were placed in a
dried round-bottomed flask containing a magnetic
stirrer bar and stirred at room temperature for 1hr.
After this arene diamine (4.5 mmole) was added, and
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IO
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