Synthesis of 6-butyl-7-methylidene-8-phenyl-5H-pyrrolo-[3,4-d]tetrazolo[1, 5-a]pyrimidin-5-one

Full text of DOI:10.1134/S1070428007090308

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 9, pp. 1419–1420. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © V.L. Gein, O.S. Panova, E.P. Tsyplyakova, L.I. Varkentin, M.I. Vakhrin, Z.L. Aliev, 2007, published in Zhurnal Organicheskoi
Khimii, 2007, Vol. 43, No. 9, pp. 1422–1423.
SHORT
COMMUNICATIONS
Synthesis of 6-Butyl-7-methylidene-8-phenyl-5H-pyrrolo-
[3,4-d]tetrazolo[1,5-a]pyrimidin-5-one
V. L. Geina, O. S. Panovaa, E. P. Tsyplyakovaa, L. I. Varkentina,
M. I. Vakhrina, and Z. L. Alievb
a Perm State Pharmaceutical Academy, ul. Lenina 48, Perm, 614990 Russia
e-mail: perm@pfa.ru
b Institute of Chemical Physics Problems, Russian Academy of Sciences, Chernogolovka, Moscow oblast, Russia
Received January 9, 2007
DOI: 10.1134/S1070428007090308
We have found that methyl 6-acetyl-4,7-dihydro-
7-phenyltetrazolo[1,5-a]pyrimidine-5-carboxylate (I)
reacts with an equimolar amount of butylamine at 130–
150°C to give in 20–30 min 6-butyl-7-methylidene-8-
phenyl-5H-pyrrolo[3,4-d]tetrazolo[1,5-a]pyrimidin-5-
one (II). Presumably, in the first stage intermediate
amine A is formed, and its enamino tautomer under-
goes intramolecular cyclization to compound II. The
latter was isolated as a yellow crystalline substance
which is insoluble in water and ethanol, soluble in
glacial acetic acid and acetonitrile on heating, and
readily soluble in DMSO and DMF.
By slow crystallization from acetonitrile we suc-
ceeded in obtaining a single crystal of compound II
suitable for X-ray analysis (see figure). The tricyclic
fragment of molecule II is planar. The double bonds
therein are localized with no appreciable conjugation
effect. All bond lengths and bond angles have their
usual values. Molecules II in crystal are linked through
intermolecular hydrogen bonds N5–H5···N4, giving
rise to centrosymmetric dimers. The distance N5···N4
is 2.908 Å, indicating that the intermolecular hydrogen
bond is not very strong.
6-Butyl-7-methylidene-8-phenyl-5H-pyrrolo-
[3,4-d]tetrazolo[1,5-a]pyrimidin-5-one (II). A mix-
ture of 5 mmol of ester I [1] and 5 mmol of butylamine
was heated at 130–150°C until gaseous products no
longer evolved (for 20–30 min). After cooling, the
mixture was treated with ethanol, and the precipitate
was filtered off and recrystallized from acetonitrile.
Yield 0.5 g (31%), mp 196–198°C. IR spectrum, ν,
Compound II displayed in the IR spectrum absorp-
tion bands belonging to stretching vibrations of the
lactam carbonyl group (1692 cm–1), secondary amino
group (3144 cm–1), and double C=C bonds (1632 cm–1).
Its 1H NMR spectrum contained signals from aromatic
protons and protons in the butyl group, doublets at
δ 4.43 and 4.95 ppm (J = 2.5 Hz) from protons in the
exocyclic methylene group, NH signal at δ 11.73 ppm,
and a singlet at δ 7.02 ppm from the 8-H proton. In the
mass spectrum of II we observed the molecular ion
peak [M]+ with m/z 322 and fragment ion peaks with
m/z 294 [M – CO]+, 245 [M – Ph]+, and 77 [Ph]+,
which are consistent with the assigned structure.
1
cm –1: 1692 (CO), 3144 (NH), 1632 (CH2=). H NMR
spectrum, δ, ppm: 4.43 d (1H, CH2=, J = 2.5 Hz),
4.95 d (1H, CH2=, J = 2.5 Hz), 7.02 s (1H, CH),
11.73 s (1H, NH), 7.41 m (5H, C6H5), 0.87 m (3H,
CH3), 1.25 m (2H, 3′-H), 1.46 m (2H, 2′-H), 3.57 m
(2H, 1′-H). Found, %: C 63.22, 63.45; H 5.51, 5.74;
O
H
O
O
H
H
N
N
N
N
N
N
N
N
MeO
Me
MeO
+
BuNH2
N
N
Bu
N
N
–MeOH
N
BuNH
N
N
N
H2C
O
Ph
CH2 Ph
Ph
I
A
II
1419

GEIN et al.
1420
O
A set of experimental reflections was acquired on
N5
a KM-4 automatic four-circle diffractometer with
χ-geometry (monochromatized MoKα irradiation, ω/2Θ
scanning to 2Θ ≤ 50.14°). Monoclinic crystals with the
following unit cell parameters: a = 7.815(2), b =
3.291(3), c = 15.766(3) Å; β = 90.96(3)°; V =
1637.4(6) Å3; M = 322.37; dcalc = 1.308 g/cm3; Z = 4;
space group P2(1)/c. Total of 2864 independent reflec-
tions (Rint 0.0208) were measured. No correction for
absorption was introduced (μ = 0.087 mm–1). The
structure was solved by the direct method using SIR92
program [2], followed by a series of calculations of
electron density maps. The positions of hydrogen
atoms were set on the basis of geometry considera-
tions. Full-matrix anisotropic refinement of the posi-
tions of non-hydrogen atoms by the least-squares pro-
cedure using SHELXL-97 program [3] was complete
at R1 = 0.0460, wR2 = 0.1163 [from 1368 reflections
with I ≥ 2σ(I)]; goodness of fit 0.889.
C2
N4
C16
C14
C3
C4
C17
C1
N1
N3
N6
C15
C5
C6
N2
H7
C7
C8
C9
C10
C13
C12
C11
Structure of the molecule of 6-butyl-7-methylidene-8-phen-
yl-5H-pyrrolo[3,4-d]tetrazolo[1,5-a]pyrimidin-5-one (II)
according to the X-ray diffraction data.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 04-03-96042).
N 25.95, 26.19. C17H18N6O. Calculated, %: C 63.34;
H 5.63; N 26.07.
REFERENCES
The IR spectrum was recorded on a Specord M-80
spectrometer from a sample of II dispersed in mineral
oil. The H NMR spectra were measured on a Varian
1. Gein, V.L., Gein, L.F., Tsyplyakova, E.P., and Rozo-
1
va, E.A., Russ. J. Org. Chem., 2003, vol. 39, p. 753.
Mercury-300 (300.056 MHz) and Bruker DRX-500
(500.13 MHz) instruments using DMSO-d6 as solvent
and TMS as internal reference. The mass spectrum
(electron impact, 70 eV) was obtained on a Finnigan
MAT INCOS-50 mass spectrometer.
2. Altomare, A., Cascarano, G., Giacovazzo, C., and
Gualardi, A., J. Appl. Crystallogr., 1993, vol. 26, p. 343.
3. Sheldrick, G.M., SHELX97. Programs for Crystal Struc-
ture Analysis, Gottingen: Univ. of Gottingen, Germany,
1998.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 9 2007