3H-Pyrido[6,7-b]-1,3,4-triazepines from 5-Aryltetrazoles

Full text of DOI:10.1023/A:1026084523746

Russian Journal of Organic Chemistry, Vol. 39, No. 4, 2003, pp. 611 612. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 4, 2003,
pp. 647 648.
Original Russian Text Copyright
2003 by Nikulin, Artamonova, Koldobskii.
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COMMUNICATIONS
Dedicated to the Correspondiny Member of the Russian Academy of Sciences
B. V. Gidaspov on occasion of his 60th anniversary
3H-Pyrido[6,7-b]-1,3,4-triazepines from 5-Aryltetrazoles
V. V. Nikulin, T. V. Artamonova, and G. I. Koldobskii
St. Petersburg State Technological Institute, St. Petersburg, 190013 Russia
Received December 20, 2002
The study of thermal transformation of N-imido-
yltetrazoles generated under conditions of phase-
transfer catalysis from 5-substituted tetrazoles and
N-arylbenzimidoyl chlorides resulted in development
of a new preparation method for previously unavail-
able 3H-1,3,4-benzotriazepines [1 7].
remained unclear whether this approach is suitable for
triazepines synthesis with triazepine ring fused not to
a benzene but to pyridine ring.
We report below on the new data showing the pos-
sibility to prepare by this procedure triazepines fused
with a puridine ring. We found that thermolysis of
N-imidoyltetrazoles obtained under conditions of the
phase-transfer catalysis from 5-aryltetrazoles and
N-(m-pyridyl)benzimidoyl chloride gave rise to pre-
viously unknown 3H-pyrido[6,7-b]-1,3,4-triazepines.
We have shown by numerous examples that the
method is of general character and can be used for
building up complex heterocyclic systems including
several triazepine rings [5, 6]. However up till now
R =
R = H (a), R = 4-Br, R = H (b), R = 4-Cl, R = H (c), R = H, R = 4-Me (d).
3H-Pyrido[6,7-b]-1,3,4-triazepines (Ia d), as also
3H-1,3,4-benzotriazepines [2, 5], are stable against
bases but are easily hydrolyzed in water solutions of
mineral acids.
2,5-Diphenyl-3H-pyrido[6,7-b]-1,3,4-triazepine
(Ia). To a mixture of 0.01 mol of 5-phenyltetrazole,
0.001 mol of tetrabutylammonium bromide, 10 ml of
10% water solution of NaOH, and 30 ml of chloro-
form was added at 20 C while stirring within 30 min
0.01 mol of N-(m-pyridyl)benzimidolyl chloride in
10 ml of chloroform. The reaction mixture was stir-
red for 4 h at 20 C, the phases were separated, the
organic layer was washed with 1% water solution of
NaOH, with water (2 10 ml), and dried with
magnesium sulfate. The chloroform was removed in a
vacuum, to the solid residue was added 20 ml of
toluene, and it was heated for 3 h to 110 C. Then
the toluene was removed in a vacuum, the residue
was recrystallized from acetonitrile. Yield 1.35 g
(57%). After additional purification by column
chromatography on silica gel (eluent carbon tetra-
At treatment of reagent Ia with methyl iodide in
the presence of potassium tert-butylate arises the
corresponding N-methyl derivative.
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612
NIKULIN et.al.
chloride ethyl acetate, 3: 2) mp 205 208 C. IR
spectrum, cm 1: 926, 984, 1001, 1026, 1055, 1076,
1121, 1167.
2,5-Dipheny-1-methylpyrido[6,7-b]-1,3,4-tri-
azepine. To a solution of 1.7 mmol of reagent Ia in
30 ml of anhydrous tetrahydrofuran was added
2 mmol of potassium tert-butylate. The reaction
mixture was stirred for 30 min at 20 C, 2.5 mmol
of methyl iodide was added thereto. The stirring was
continued for 2 h at 20 C, 150 ml of water was added,
and the separated precipitate was filtered off. Yield
5-(4-Bromophenyl)-2-phenyl-3H-pyrido-[6,7-b]-
1,3,4-triazepine (Ib). Yield 17%. mp 221 222 CC.
1:
IR spectrum, cm 935, 950, 990, 1020, 1035, 1075,
1120, 1170, 1180, 1230, 1270, 1290, 1325, 1390,
1450, 1475, 1495, 1565, 1600, 1635, 2865, 2935,
1
0.334 g (63%), mp 198 200 C. IR spectrum, cm :
1
3085, 3335. H NMR spectrum (DMSO-d6), , ppm:
920, 935, 950, 975, 990, 1010, 1025, 1045, 1060,
1080, 1090, 1140, 1165, 1180, 1190, 1240, 1260,
1280, 1315, 1330, 1440, 1450, 1475, 1495, 1550,
1580, 1595, 2835, 2870, 2930, 2960, 3005, 3035,
3070. 1H NMR spectrum (DMSO-d6), , ppm: 3.15 s
(3H, CH3), 7.39 8.45 m (13H arom). Found, %:
C 77.09; H 5.25; N 17.80. C20H16N4. Calculated, %:
C 76.92; H 5.13; N 17.95.
7.3 8.4 m (12H arom) 9.5 s (1H, NH). Found, %:
C 60.49; H 3.27; N 14.87. C19H13BrN4. Calculated,
%: C 60.48; H 3.45; N 14.85.
2-Phenyl-5-(4-chlorophenyl)-3H-pyrido-[6,7-b]-
1,3,4-triazepine (Ic). Yield 31%. mp 204 208 C. IR
1
spectrum, cm : 925, 950, 990, 1010, 1020, 1035,
1060, 1080, 1095, 1120, 1170, 1185, 1240, 1275,
1295, 1330, 1400, 1450, 1475, 1495, 1560, 1585,
IR spectra were recorded on spectrometer UR-20
1
1
1605, 1640, 2865, 2935, 3085, 3350. H NMR spec-
from KBr pellets, H NMR spectra were registered
trum (DMSO-d6), , ppm: 7.3 8.4 m (12H arom),
9.0 s (1H, NH). Found, %: C 68.63; H 4.05;
N 16.72. C19H13ClN4. Calculated, %: C 68.57;
H 3.91; N 16.84.
on spectrometer Bruker AC-200. The purity and
homogeneity of compounds obtained was tested by
TLC on Silufol UV-254 plates, eluent mixture of
carbon tetrachloride and ethyl acetate, 3: 2. The study
was carried out under financial support of the
Ministry of Education of Russian Federation (Federal
Program Integratsiya , grant no. I 0667).
2-(4-Tolyl)-5-phenyl-3H-pyrido[6,7-b]-1,3,4-tri-
azepine (Id). Yield 25%. mp 212 213 C. IR spec-
1
trum, cm : 930, 950, 985, 1010, 1025, 1040, 1060,
1085, 1095, 1120, 1170, 1180, 1200, 1220, 1235,
1280, 1295, 1320, 1330, 1400, 1415, 1455, 1475,
1505, 1525, 1565, 1605, 1735, 2870, 2940, 3045,
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1
3065, 3350. H NMR spectrum (DMSO-d6), , ppm:
2.4 s (3H CH3), 7.2 8.2 m (12H arom), 9.4 s (1H,
NH). Found, %: C 77.01; H 5.27; N 17.93.
C20H16N4. Calculated, %: C 76.92; H 5.13; N 17.95.
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Acid hydrolysis of 2,5-diphenyl-3H-pyrido-[6,7-
b]-1,3,4-triazepinea (Ia). A mixture of 1.2 mmol of
triazepine Ia, 10 ml of 17% hydrochloric acid was
heated for 2 h to 100 C, cooled to 5 C, the separated
precipitate of benzoic acid was filtered off to obtain
0.058 g (40%) of benzoic acid, mp 123 C. To the
filtrate was added 10% water solution of NaOH till
pH 10 12, the separated precipitate was filtered off,
washed with water (10 ml), and dried in air to obtain
0.212 g (89%) of 3-amino-2-benzylpyridine, mp
99 101 C (from hexane) [8].
7. Morgenstern, O., Pharmazie, 2000, vol. 55, p. 871.
8. Littell, R. and Allen, D.S., J. Med. Chem., 1965,
vol. 8, p. 722.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 4 2003