αꢀUreidoalkylation of thiosemicarbazide
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 5, May, 2006
871
Synthesis of 4,5ꢀbis(3ꢀthiosemicarbazido)imidazolidinꢀ2ꢀones
a—f (general procedure). A solution of an appropriate DHI
a—f (0.02 mol) in water (20 mL) was acidified with conc. HCl
Table 1. The mass and 13C NMR spectra of compound 5b are
given in Tables 4 and 5, respectively.
4
3
(
Synthesis of 4,5ꢀbis(guanidinoamino)imidazolidinꢀ2ꢀones
7a—c (general procedure). A solution of an appropriate DHI
3a—c (0.02 mol) in water (20 mL) was acidified with conc. HCl
(0.2 mL) and heated to 80 °C. Aminoguanidine hydrochloride
(0.04 mol) was added thereto. The reaction mixture was kept at
80 °C for 1 h and then at 4 °C for 16 h. The precipitates that
formed were filtered off and crystallized from MeOH to give
4,5ꢀbis(guanidinoamino)imidazolidinꢀ2ꢀone dihydrochloride
(7a), 4,5ꢀbis(guanidinoamino)ꢀ1,3ꢀdimethylimidazolidinꢀ2ꢀone
dihydrochloride (7b), and 1,3ꢀdiethylꢀ4,5ꢀbis(guanidinoamiꢀ
no)imidazolidinꢀ2ꢀone dihydrochloride (7c).
0.2 mL) and then thiosemicarbazide (0.04 mol) was added. The
reaction mixture was stirred at 80 °C for 1 h. The precipitates
that formed were filtered off and washed with hot methaꢀ
nol—water (1 : 1) to give 4,5ꢀbis(3ꢀthiosemicarbazido)imidꢀ
azolidinꢀ2ꢀone (4a), 1,3ꢀdimethylꢀ4,5ꢀbis(3ꢀthiosemicarbaziꢀ
do)imidazolidinꢀ2ꢀone (4b), 1,3ꢀdiethylꢀ4,5ꢀbis(3ꢀthiosemicarbꢀ
azido)imidazolidinꢀ2ꢀone (4c), 1ꢀmethylꢀ4,5ꢀbis(3ꢀthiosemiꢀ
carbazido)imidazolidinꢀ2ꢀone (4d), 1ꢀethylꢀ4,5ꢀbis(3ꢀthioꢀ
semicarbazido)imidazolidinꢀ2ꢀone (4e), and 3ꢀethylꢀ1ꢀmethylꢀ
4
,5ꢀbis(3ꢀthiosemicarbazido)imidazolidinꢀ2ꢀone (4f). Their
yields and selected physicochemical characteristics are summaꢀ
Their yields and selected physicochemical characteristics
are summarized in Table 3. Their H NMR spectra are given in
1
1
rized in Table 3. Their H NMR spectra are given in Table 1.
The mass and 13C NMR spectra of compound 4b are given in
Tables 4 and 5, respectively.
Table 1. The mass spectrum of compound 7c is given in Table 4.
13
The C NMR spectrum of compound 7b is given in Table 5.
Synthesis of 1,3ꢀdialkylꢀ4ꢀ(guanidinoimino)imidazolidinꢀ2ꢀ
ones 8b,c (general procedure). A solution of an appropriate DHI
3b,c (0.02 mol) in MeOH (50 mL) was acidified with conc. HCl
(0.2 mL) and heated to 60 °C. Aminoguanidine hydrochloride
(0.02 mol) was slowly added in portions for 15 min. The reaction
mixture was stirred at 70—75 °C for 1 h and then kept at 4 °C
for 16 h. The crystalline precipitates that formed were filtered
off and recrystallized from MeOH. The yields of 4ꢀ(guanidinoꢀ
imino)ꢀ1,3ꢀdimethylimidazolidinꢀ2ꢀone hydrochloride (8b) and
1,3ꢀdiethylꢀ4ꢀ(guanidinoimino)imidazolidinꢀ2ꢀone hydrochloꢀ
ride (8c) were 78 and 72%, respectively.
Synthesis of 5,7ꢀdialkylꢀ3ꢀthioxoperhydroimidazo[4,5ꢀe]ꢀ
[
1,2,4]triazinꢀ6ꢀones 5b,c (general procedure). A solution of 1,3ꢀ
dialkylꢀ4,5ꢀdihydroxyimidazolidinꢀ2ꢀone 3b,c (0.02 mol) in
MeOH (50 mL) was acidified with conc. HCl (0.2 mL) and
heated to 50 °C. Then thiosemicarbazide (0.02 mol) was slowly
added in portions for 0.5 h. The reaction mixture was stirred at
7
0—75 °C for 1 h and kept at 4 °C for 16 h. Crystalline precipiꢀ
tates of compounds 5b,c that formed were filtered off and reꢀ
crystallized from MeOH. The yields of 5,7ꢀdimethylꢀ3ꢀthioxoꢀ
perhydroimidazo[4,5ꢀe][1,2,4]triazinꢀ6ꢀone (5b) and 5,7ꢀdiꢀ
ethylꢀ3ꢀthioxoperhydroimidazo[4,5ꢀe][1,2,4]triazinꢀ6ꢀone (5c)
were 96 and 90%, respectively.
Their yields and selected physicochemical characteristics
1
Their yields and selected physicochemical characteristics
are summarized in Table 3. Their H NMR spectra are given in
1
13
are summarized in Table 3. Their H NMR spectra are given in
Table 1. The C NMR spectrum of compound 8b is given in
Table 5.
Table 4. Mass spectra of compounds 4b, 5b, and 7c
This work was financially supported by the Russian
Academy of Sciences (Program for Basic Research of the
Division of Chemistry and Materials Sciences of the Rusꢀ
sian Academy of Sciences "Biomolecular and Medicinal
Chemistry").
Product
MS, m/z (I (%))
4
b
201 (30) [M+ – NH NHC(S)NH ], 184 (19), 170
2
2
(
19), 144 (19), 112 (100), 91 (58), 82 (25), 60 (48),
8 (97)
201 (38) [M ], 184 (4), 170 (30), 144 (13), 126 (7),
12 (100), 97 (4), 89 (12), 83 (11), 69 (11), 58 (31)
5
+
5
7
b
c
References
1
+
212 (90) [M – NH NHC(NH)NH ], 180 (12), 168
2
2
1
2
. H. Petersen, Synth., 1973, 5, 273.
. A. N. Terpigorev and S. B. Rudakova, Zh. Org. Khim., 1998,
(
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1
5
14 (47), 98 (85), 97 (56), 69 (63),
8 (81), 56 (100)
3
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3
. A. N. Kravchenko, A. S. Sigachev, E. Yu. Maksareva, G. A.
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Table 5. 13C NMR spectra ([ H ]DMSO) of compounds 4b, 5b,
2
6
7
b, and 8b
5
4, 691].
Product
δ
4
. V. A. Eres´ko, L. V. Epishina, O. V. Lebedev, M. V.
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4
5
7
8
b
b
b
b
33.4 (2 Me), 78.5 (2 CH), 163.7 (C=O), 187.8
+
(
C=NH2
)
27.1 (Me), 27.4 (Me), 63.7 (CH), 69.0 (CH),
58.0 (C=O), 184.0 (C=S)
28.422 (2 Me), 73.359 (2 CH), 158.455 (C=O),
5
6
1
1
962, 27, 2181.
. G. A. Gazieva, A. N. Kravchenko, O. V. Lebedev, K. A.
Lyssenko, M. O. Dekaprilevich, V. M. Men´shov, Yu. A.
Strelenko, and N. N. Makhova, Mendeleev Commun.,
+
1
59.443 (C=NH2
)
26.1 (Me), 29.7 (Me), 47.8 (CH ), 151.7 (C=O),
2
1
55.7 (C=N), 156.6 (C=N)
2
001, 4, 138.