Synthesis of 3-aryl(hetaryl)-4-(2-cyanoprenyl)-Δ 2-1,2,4-triazolin-5-ones [3]

Full text of DOI:10.1023/B:COHC.0000014420.78885.e9

Chemistry of Heterocyclic Compounds, Vol. 39, No. 11, 2003
SYNTHESIS OF 3-ARYL(HETARYL)-
2
4
-(2-CYANOPHENYL)-∆ -1,2,4-TRIAZOLIN-5-ONES
1
2
1
3
A. P. Stankevicius , P. B. Terentiev , L. N. Janushene , and A. A. Zhevzhikoviene
2
Keywords: O-arylsulfonyl derivatives of isatin 3-monooxime, 3-aryl(hetaryl)-4-(2-cyanophenyl)-∆ -
1
,2,4-triazolin-5-one.
1
-Unsubstituted O-arylsulfonyl derivatives of isatin 3-oximes in the presence of aliphatic and aromatic
amines readily rearrange with breaking of the intercarbonyl bond to form N-(2-cyanoaryl)-N'-R-carbamides [1].
Hypothesizing that the corresponding semicarbazides will be formed upon reaction with substituted hydrazines,
we studied the reaction of arylsulfonates 1a-c with carboxylic acid hydrazides. In this case, we have established
that even under relatively mild conditions (brief heating of the components in dioxane in the presence of
triethylamine), compounds with molecular masses 18 units less than expected for the corresponding
semicarbazides were formed in rather good yields. This indicated that under the reaction conditions,
cyclodehydration of compounds 1a-c occurred to form 3-aryl(hetaryl)-5-oxo(4H-4-(2-cyanophenyl)-1,2,4-
triazolines 2a-c.
N
OH
N
OSO Ar
2
ArSO Cl
2
o
–
5 C, NaOH
1
O
O
R CONHNH
2
N
R
N
R
1
a–c
CN
R = Me
O
N
NH
N
R1
2
a–c
1
a, b R = H, c R = Me, a Ar = Ph, b, c Ar = p-MeC
6
4
H ;
1
1
1
2
a R = p-MeOC
6
H , b R = 4-Py, c R = Ph
4
In fact, the molecular ion peaks had the maximum intensity in their mass spectra, indicating a cyclic
structure for the compounds, while the fragmentation processes were mainly connected with elimination of
predominantly CO molecules, 2-NCC
6
H NCO, and also R'CN (m/z 159), which would not be possible in the
4
case of a linear structure. We should note that N-substituted tosylate 1c did not react with the hydrazides used,
which allows us to hypothesize formation of highly reactive intermediate 2-cyanophenyl isocyanates under the
reaction conditions. Investigations are continuing.
_
_________________________________________________________________________________________
1
Institute of Cardiology, Kaunas Medical University, Kaunas 3007, Lithuania; e-mail: carsynt@kmu.lt.
Chemistry Department, M. V. Lomonosov Moscow State University, Moscow 119899, Russia; e-mail:
2
3
petr@ms-bioorg.chem.msu.ru. Kaunas Medical University, Kaunas 3000, Lithuania; e-mail: vpaul@kmu.lt.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1731-1732, November, 2003. Original
article submitted October 23, 2003.
0
009-3122/03/3911-1525$25.00©2003 Plenum Publishing Corporation
1525

2
4
-(2-Cyanophenyl)-3-(4-methoxyphenyl)-∆ -1,2,4-triazolin-5-one (2a). Mixture of O-benzene-
sulfonate 1a (3.02 g, 10 mmol) [1], p-methoxybenzoic acid hydrazide (3.32 g, 20 mmol), triethylamine (1 ml) in
dioxane (10 ml) was heated for 45 min. After cooling down to room temperature, the mixture was diluted with
water (20 ml), the substance was filtered off, washed with water, and recrystallized from acetic acid with
+
activated carbon. Obtained 1.2 g (41%) of triazolinone 2a; mp 302-303°C. Mass spectrum, m/z (I, %): 292 [M]
+
+
+
1
+
(
100), 277 [M–CH
3
] (7), 264 [M–CO] (6), 148 [M-144] (11), 144 [2-NCC
6
H NCO] (7), 133 [R CN] (16),
4
1
19 (5), 105 (4), 103 (4), 90 (4), 76 (5).
2
4
-(2-Cyanophenyl)-3-(4-pyridyl)-∆ -1,2,4-triazolin-5-one (2b) was obtained similarly from
benzenesulfonate 1a (3.02 g, 10 mmol), isonicotinic acid hydrazide (1.5 g, 11 mmol) and triethylamine (2 ml) in
dioxane (10 ml). The mixture was boiled for 10 min and 1.1 g (42%) of compound 2a were obtained;
+
1
+
mp >300°C (acetic acid). Mass spectrum, m/z (I, %): 263 [M] (100), 159 [M–R CN] (4), 144
+
1
+
+
1
+
[
7
2-NCC
6
H NCO] (8), 131 [M–R CN–CO] (17), 119 [M-144] (70), 104 [R CN] (7), 103 (10), 92 (10), 91 (9),
4
8 (24), 76 (11), 50 (17).
2
4
-(2-Cyanophenyl)-3-phenyl-∆ -1,2,4-triazolin-5-one (2c) was obtained similarly by boiling a mixture
of tosylate 1b (3.16 g, 10 mmol) [1], benzoic acid hydrazide (1.5 g, 11 mmol) and triethylamine (2 ml) in
+
dioxane (10 ml) for 45 min. Yield 1.2 g (46%); mp >300°C (dioxane). Mass spectrum, m/z (I, %): 262 [M]
+
1
+
+
1
+
(
1
100), 234 [M–CO] (6), 159 [M–R CN] (3), 144 [2-NCC
6
H NCO] (3), 131 [M–R CN–CO] (6), 118 [M–
4
+
1
+
44] (70), 103 [R CN] (15), 91 (14), 89 (10), 77 (11), 76 (10).
REFERENCES
1
.
A. P. Stankevicius, P. B. Terentiev, L. N. Janushene, and P. V. Vainauskas, Khim. Geterotsikl. Soedin.,
868 (2003).
1
1
526