Synthesis of 3-r-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4] triazolo[4,3-a]azocines

Full text of DOI:10.1007/s10593-011-0680-9

Chemistry of Heterocyclic Compounds, Vol. 46, No. 11, February, 2011 (Russian Original Vol. 46, No. 11, November, 2010)
SYNTHESIS OF 3-R-6,7,8,9,10,11-HEXAHYDRO-5H-5,9:7,11-
DIMETHANO[1,2,4]TRIAZOLO[4,3-a]AZOCINES
E. A. Knyazeva1*, M. Yu. Skomorohov1, and Yu. N. Klimochkin1
Keywords:
3-R-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4]triazolo[4,3-a]azocines,
lactim
ethers, 5-methoxy-4-azatricyclo[4,3,1,13,8]undec-4-ene.
Lactim ethers of monocyclic lactams react with hydrazides to give amidrazones but 1,2,4-triazoles only
upon prolonged heating [1, 2]. We have found that treatment of 5-methoxy-4-azatricyclo[4.3.1.13,8]undec-4-ene
(1) with acid hydrazides gives the substituted triazoles 2a-d, even at room temperature. The ease of the
cyclization can be due to the lowering of resonance delocalization of the unshared electron pair of the
endocyclic nitrogen atom in the intermediately formed amidrazone 3. This is confirmed by the ability of
4-azatricycl[4.3.1.13,8]undecan-5-one to form a stable hydrochloride [3].
H
N
H
N
O
Me
N
N
N
R
O
N
O
N
R
R
+
N
H
NH2
1
2a–d
3
a R = CF3, b R = Ph, c R = 3-Py, d R = Ad
1
IR spectra were taken on a Shimadzu FTIR-8400S spectrometer for KBr tablets. H and 13C NMR
spectra were recorded on a Bruker AM-400 spectrometer (400 and 100 MHz respectively) using CDCl3. Mass
spectra were obtained on a Finnigan Trace DSQ chromato-mass spectrometer with an ionization energy of 70
eV. Elemental analysis was carried out on a Euro Vector EA-3000 automatic CHNS analyzer.
5-Methoxy-4-azatricyclo[4.3.1.13,8]undec-4-ene (1) was prepared by a known method [4].
3-Trifluoromethyl-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4]triazolo[4,3-a]azocine (2a).
A mixture of compound 1 (1 g, 5.6 mmol) and trifluoroacetic acid hydrazide (5.7 mmol) in methanol (6 ml) was
held for 1 day at room temperature. The precipitate formed was filtered off and recrystallized from o-xylene.
Yield 0.63 g (44%) as white crystals with mp 136-138ºC. IR spectrum, , cm-1: 2923, 1639, 1504, 1442, 1353,
1
1245, 1184, 1141, 1118, 1002. H NMR spectrum, , ppm: 4.58-4.59 (1H, m, H-1); 3.62-3.63 (1H, m,
_______
* To whom correspondence should be addressed, e-mail: orgchem@samgtu.ru.
1Samara State Technical University, Samara 443100, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1731-1733, November 2010.
Original article submitted August 2, 2010.
0009-3122/11/4611-1407©2011 Springer Science+Business Media, Inc.
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H-7); 1.75-2.28 (12H, m, H-8 to H-14). Mass spectrum, m/z (Irel, %): 257 [M]+ (100), 214 (14), 188 (25), 164
(33), 91 (14), 79 (15), 53 (11). Found, %: C 56.15; H 5.41; N 16.38. C12H14F3N3. Calculated, %: C 56.03;
H 5.49; N 16.33.
3-Phenyl-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4]triazolo[4,3-a]azocine (2b) was
prepared similarly to compound 2a. Yield 40% as white crystals with mp 178-181ºC (toluene). IR spectrum, ,
1
cm-1: 2920, 1639, 1477, 1446, 1253, 1215, 1091, 771, 698. H NMR spectrum, , ppm: 7.48-7.56 (5H, m, Ph);
4.47-4.48 (1H, m, H-1); 3.61-3.63; (1H, m, H-7); 1.79-2.24 (12H, m, H-8 to H-14). Mass spectrum, m/z (Irel, %):
265 [M]+ (100), 196 (12), 172 (34), 159 (7), 104 (12), 91 (13), 77 (23). Found, %: C 76.89; H 7.31; N 15.80.
C17H19N3. Calculated, %: C 76.95; H 7.22; N 15.84.
3-(3-Pyridyl)-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4]triazolo[4,3-a]azocine (2c) was
prepared similarly to compound 2a. Yield 22% as white crystals with mp 172-174ºC (acetonitrile). IR spectrum,
, cm-1: 2916, 1593, 1469, 1442, 1384, 1253, 1087, 817, 717. 1H NMR spectrum, , ppm (J, Hz): 8.62-8.66 (2H,
m, H-2",6" ); 7.81-7.84 (1H, dt, 1J = 7.5, 2J = 1.8, H-4"); 7.37 (1H, dd, 1J = 7.5, 2J = 5.5, H-5"); 4.39-4.41 (1H,
13
m, H-1); 3.61-3.63 (1H, m, H-7); 1.70-2.25 (12H, m, H-8 to H-14). C NMR spectrum, , ppm: 160.3, 151.1,
150.8, 149.4, 136.8, 124.0, 123.8, 49.5, 35.0, 34.5, 32.7, 30.1, 26.7. Mass spectrum, m/z (Irel, %): 265 [M]+
(100), 173 (46), 105 (19), 93 (20), 77 (23). Found, %: C 72.23; H 6.92; N 20.85. C16H18N4. Calculated, %:
C 72.15; H 6.81; N 21.04
3-(1-Adamantyl)-6,7,8,9,10,11-hexahydro-5H-5,9:7,11-dimethano[1,2,4]triazolo[4,3-a]azocine (2d)
was prepared similarly to compound 2a. Yield 44% as white crystals with mp 313-314ºC (o-xylene). IR
spectrum, , cm-1: 2904, 1635, 1596, 1512, 1446, 1373, 1253, 1103. 1H NMR spectrum, , ppm: 4.82-4.83 (1H,
m, H-1); 3.54-3.55 (1H, m, H-7); 1.76-2.26 (27H, m, H-8 to H-14, H-Ad). 13C NMR spectrum, , ppm: 160.5,
142.5, 50.0, 36.5, 35.2, 34.6, 32.6, 30.7, 29.6, 27.0, 26.6. Mass spectrum, m/z (Irel, %): 324 [M]+ (100), 267 (28),
228 (13), 91 (10), 79 (13). Found, %: C 78.08; H 8.99; N 12.93. C21H29N3. Calculated, %: C 77.97; H 9.04;
N 12.99.
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