4940 Soleiman-Beigi et al.
Asian J. Chem.
(1.0 mmol) and carbon disulfide (3.0 mmol) in DMF (2.0 mL)
was stirred for 15 min at room temperature, the mixture of
reaction then was heated at 70 ºC for appropriated time until
complete ring closure (4 h).After cooling to room temperature,
alkyl halide (1.2 mmol) and Et3N (4 mmol) were added to
mixture of reaction and stirred again at room temperature until
completion of reaction as monitored by TLC (ethyl acetate:
n-hexane (1:2). Then the solvent was evaporated in vacuo and
the crude product was purified by preparative TLC (silica gel,
eluent EtOAc:n-hexane 1:2) to obtain pure product.
MHz, CDCl3): δ 37.30, 121.04, 127.71, 129.58, 138.64,
160.65, 163.96, 178.0. Anal. calcd. for C10H8N2O3S: C, 50.
84; H, 3.41; N, 11.86. Found: C, 51. 08; H, 3.67; N, 12.04.
1,2-Bis((5-phenyl-1,3,4-oxadiazole-2-yl)thio) ethane
(Table-2, entry 13): m.p. 122-125 ºC. IR (KBr, νmax, cm–1):
1
1604, 1087. H NMR (400 MHz, CDCl3): δ 3.86 (s, 4H,
-CH2), 7.55 (m, 6H, Ar-H), 8.04 (m, 4H, Ar-H). 13C NMR
(100 MHz, CDCl3): δ 36.54, 124.60, 126.51, 128,01, 131.55,
164.03, 165.60. MS (EI, 70 eV): m/z (%) 382 (62), 205 (100),
145 (42), 105 (41), 77 (57). Anal. calcd. for C19H17N4O2S2: C,
57. 41; H, 4.31; N, 14.10. Found: C, 57. 21; H, 4.57; N, 13.88.
Ethyl-[5-(4-chlorophenyl)-1,3,4-oxadiazol)-2-ylthio]
acetate (Table-2, entry 2): m.p. 85-86 ºC34. IR (KBr, νmax
,
RESULTS AND DISCUSSION
cm–1): 1736, 1602, 1200, 1088. 1H NMR (400 MHz, CDCl3):
δ 1.31 (t, J = 7.2 Hz, 3H, -CH3), 4.12 (s, 2H, -SCH2), 4.27 (q,
J = 7.2 Hz, 2H, -OCH2), 7.49 (d, J = 8.4 Hz, 2H, Ar-H), 7.94
These issues have prompted us to investigate the synthesis
of 2-alkylthio-1,3,4-oxadiazole in one-pot and mild solution
conditions from acid hydrazides and carbon disulfide. In this
work, we have explored an one-pot method for chemoselective
synthesis of 2-alkylthio-1,3,4-oxadiazole derivatives from acid
hydrazides (Scheme-II).
13
(d, J = 8.4 Hz, 2H, Ar-H). C NMR (100 MHz, CDCl3): δ
14.09, 34.40, 62.45, 121.92, 127.96, 129.47, 138.03, 163.23,
165.25, 167.30.
2-(Methylthio)-5-(4-methylphenyl)-1,3,4-oxadiazole
(Table-2, entry 6): m.p. 50-51 ºC. IR (KBr, νmax, cm–1): 1611,
1
1477, 1087. H NMR (300 MHz, CDCl3): δ 2.42 (s, 3H,
O
N
N
1) DMF
-CH3), 2.78 (s, 3H, Ar-CH3), 7.30 (d, J = 8.1, 2H, Ar-H), 7.90
(d, J = 8.1, 2H, Ar-H). 13C NMR (75 MHz, CDCl3): δ 14.66,
21.63, 120.87, 126.61, 129.72, 142.17, 164.3, 165.60.
2-(Ethylylthio)-5-phenyl-1,3,4-oxadiazole (Table-2,
entry 8): m.p. 46-48 ºC. IR (KBr, νmax, cm–1): 1605, 1086. 1H
NMR (400 MHz, CDCl3): δ 1.53 (t, J = 7.6 Hz, 3H, -CH3),
3.33 (q, 2H, J = 7.6 Hz, -SCH2), 7.52 (m, 3H, Ar-H), 8.02 (m,
2H, Ar-H). 13C NMR (100 MHz, CDCl3): δ 14.76, 27.04,
123.68, 126.61, 129,01, 131.57, 164.33, 165.66. MS (EI, 70
eV): m/z (%) = 206 (95), 178 (42), 145 (67), 105 (100), 77
(84).Anal. calcd. for C10H10N2OS: C, 58. 23; H, 4.89; N, 13.58.
Found: C, 58. 10; H, 4.97; N, 13.70.
+
CS2
R
NHNH2
2) R'-X or X-R'-X
Et3N
R
SR'
O
Scheme-II
To optimize reaction conditions, reaction of benzhy-
drazide and CS2 at catalyst-free condition in DMF was studied
as model reaction. The reaction mixture was stirred for 0.5 h
in room temperature, then the temperature was increased to
70 ºC for 3.5 h. After completion of reaction, ethyl iodide we
added to mixture of reaction at room temperature in the
presence of some different bases as the results are presented
in Table-1.
2-(Allylthio)-5-(4-chlorophenyl)-1,3,4-oxadiazole
(Table-2, entry 9): m.p. 59-61 ºC. IR (KBr, νmax, cm–1): 1640,
1603, 1087. 1H NMR (300 MHz, CDCl3): δ 3.93 (d, J = 8.0
Hz, 2H, -SCH2), 5.23 (d, J = 9.9, 1H, C=CH), 5.40 (d, J =
15.9, 1H, C=CH), 6.01 (m, 1H, CH=C), 7.47 (d, J = 6.7, 2H,
Ar-H), 7.94 (d, J = 6.7, 2H,Ar-H). 14C NMR (75 MHz, CDCl3):
δ 35.25, 119.89, 122.10, 127.90, 129.43, 131.61, 137.89,
163.99, 165.02. MS (EI, 70 eV): m/z (%) 252 (28), 179 (18),
139 (100), 115 (51), 82 (54). Anal. calcd. for C11H9N2OSCl:
C, 52. 28; H, 3.59; N, 11.08. Found: C, 52. 11; H, 3.37; N,
11.22.
TABLE-1
SEEKING THE SUITABLE BASE FOR THE ONE-POT
SYNTHESIS OF 2-ETHYLTHIO-5-PHENYL-1,3,4-
OXADIAZOLE FROM BENZHYDRAZIDE IN 6 h
Entry
Base
Yield (%)a
1
2
3
4
5
6
7
None
KF/Al2O3
TBAHb
KOH
NaOH
Et3N
DABCO
–
43
68
21
11
98
80
2-(Benzylthio)-5-phenyl-1,3,4-oxadiazole (Table-2,
entry 11): m.p. 92-94 ºC. IR (KBr, νmax, cm–1): 1613, 1585
aIsolated yields; btetra n-butyl ammonium hydroxide (25 % in water)
1
1087. H NMR (400 MHz, CDCl3): δ 4.54 (s, 2H, -SCH2),
7.27-7.99 (m, 10H, Ar-H). 13C NMR (100 MHz, CDCl3): δ
36.85, 123.60, 126.67, 128.14, 128.84, 129.06, 129.20, 131.68,
135.64, 163.89, 165.84. MS (EI, 70 eV): m/z (%) 268 (12),
206 (76), 178 (30), 145 (63), 105 (100), 91 (45), 77 (85). Anal.
calcd. for C15H12N2OS: C, 67. 14; H, 4.51; N, 10.44. Found:
C, 67. 31; H, 4.77; N, 10.21.
As shown in Table-1, this procedure dose not proceeds
properly at the presence of strong bases such as KF/Al2O3,
KOH, NaOH and TBAH (Table-1, entries 2-5). Furthermore,
no product was observed in the base-free condition (Table-1,
entry 1). While at the presence of organo bases such as Et3N
and DABCO, 2-ethylthio-5-phenyl-1,3,4-oxadiazole was
obtained in high yields (Table-1, entries 6 and 7). Herein, Et3N
was selected as suitable and accessible base.
2-((5-(4-Chlorophenyl)-1,3,4-oxadiazole-2-yl)thio)acetic
acid (Table-2, entry 12): m.p. 148-150 ºC. IR (KBr, νmax, cm–1):
3200-2400, 1736, 1610. 1H NMR (300 MHz, CDCl3) δ 3.05
(s, 2H, -SCH2), 7.47 (d, J = 8.43 Hz, 2H, Ar-H), 7.86 (d, J =
8.45 Hz, 2H, Ar-H), 13.02 (s, 1H, COOH). 13C NMR (100
To test the generality of this procedure in optimized
conditions, we have examined the reaction of acid hydrazides
with CS2 and a variety kind of alkyl halides such as alkyl,