Synthesis of new heterocyclic system, pyrido[3,2-e][1,3]thiazine by mannich reaction

Full text of DOI:10.1134/S1070428012080192

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 8, pp. 1135−1136. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.D. Dyachenko, A.A. Nikishin, A.D. Dyachenko, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 8, pp. 1135−1136.
SHORT
COMMUNICATIONS
Synthesis of New Heterocyclic System,
Pyrido[3,2-е][1,3]thiazine by Mannich Reaction
V. D. Dyachenko, A. A. Nikishin, and A. D. Dyachenko
Taras Shevchenko Lugansk National University, Lugansk, 91011 Ukraine
е-mail: chem@luguniv.edu.ua
Received March 20, 2012
DOI: 10.1134/S1070428012080192
Mannich reaction is successfully used in the
syntheses of substituted triazolo[3,4-b]-1,3,5-thia-
diazines [1], pyrido[1,2-a]-1,3,5-triazines [2], and
The aminomethylation of morpholinium 4,4-dimethyl-
6-oxo-3,5-dicyano-1,4,5,6-tetrahydropyridine-2-thiolate
(I) with formaldehyde (II) and primary amines IIIa, IIIb
under the conditions of Mannich reaction [4] resulted in
the formation of a new heterocyclic system, 4-imino-5,5-
dimethyl-7-oxo-3-benzyl- [or 3-(furan-2-ylmethyl)]-
3
,7-diazabicyclo[3.3.1]-nonanes [3]. To the aminometh-
ylation in [1] substituted 1,3,5-triazole-2-thiols were
subjected, and in [2, 3], substituted 2(1Н)-thioxopyridine-
3
6
,4,5,6,7,8-hexahydro-2Н-pyrido-[3,2-е][1,3]thiazine-
-carbonitriles (IVа, IVb).
3
-carbonitriles. In the latter compounds the cyano group
was not involved in chemical transformation in the course
of aminomethylation.
The mechanism of the discovered reaction, the range
NH
Me
NC
Me
Me
NC
Me
HCHO, H N
R
2
CN
II
IIIа, IIIb
N
R
_
+
O
N
H
S H N
O
O
N
S
2
H
I
IVа, IVb
R = Ph (а), furan-2-yl (b).
of its applicability, and the chemical and biological char-
acteristics of compounds IVа, IVb are under study and
will be published elsewhere.
hexahydro-2Н-pyrido[3,2-е][1,3]-thiazine-6-carboni-
trile (IVа). Amixture of 1.1 ml (10 mmol) of benzylamine
(IIIа) and 3.6 ml (40 mmol) of 37% formaldehyde water
Morpholinium 4,4-dimethyl-6-oxo-3,5-dicyano-
,4,5,6-tetrahydropyridine-2-thiolate (I) was obtained
solution in 15 ml of ethanol was heated to boiling, and
then 2.94 g (10 mmol) of salt I was added, and the mixture
was boiled for 40 min. From the boiling reaction mixture
crystalline product IVa precipitated, which was filtered off
on cooling, washed with ethanol and hexane. Yield 1.73 g
(53%), yellow powder, mp 290–293°С. IR spectrum, ν,
1
by procedure [5]. Yield 2.7 g (91%), mp 213–215°С. IR
–1
spectrum, ν, cm : 3353 (NH), 2257, 2188 (C≡N), 1674
1
(
1
CONH). Н NMR spectrum, δ, ppm: 1.00 (3Н, Me),
.22 (3Н, Me), 3.27 m (4Н, CH NCH ), 3.84 m (4Н,
2 2
5
+
CH OCH ), 4.18 s (1Н, C H), 7.51 br.s (2Н, NH ),
–1
2
2
2
cm : 3422, 3330 (NH), 2246 (C≡N), 1664 (CONH).
1
0.47 br.s (1Н, NH). Found, %: С 52.91; Н 6.05; N 18.94.
1
Н NMR spectrum, δ, ppm : 1.09 (3Н, Me), 1.14 (3Н,
C H N O S. Calculated, %: С 53.04; Н6.16; N 19.03.
2
1
3
18
4
2
Me), 3.78 d, 3.94 d (1Н each, NCH , J 15.0 Hz), 4.09 s
(1Н, Н6), 4.97 d, 5.53 d (1Н each, SCH N, 2J 15.0 Hz),
2
3
-Benzyl-4-imino-5,5-dimethyl-7-oxo-3,4,5,6,7,8-
2
1135

1136
DYACHENKO et al.
7
.15–7.25 m (2Н, Ph), 7.27–7.48 m (3Н, Ph), 8.91 br.s
Н 5.05; N 17.54. C H N O S. Calculated, %: С56.95;
1
5
16
4
2
(
1Н, NH), 9.10 br.s (1Н, NH). 13С NMR spectrum, δ,
ppm: 21.90, 23.50, 36.42, 50.95, 54.08, 55.86, 60.48,
17.15, 127.88, 128.32, 129.20, 135.05, 171.95, 173.27,
92.95. Mass spectrum, m/z (I %): 328(4) [M + 2]+,
Н5.10; N 17.71. M 316.385.
IR spectra were recorded on an instrument FIR-
spectrometer Spectrum One (Perkin Elmer) from pellets
1
1
3
1
with KBr, Н NMR spectra were registered on a spec-
rel,
+
+
27(11) [M + 1] , 326(48) [M] , 284(14), 235(9) [M –
trometer Bruker DR-500 (500.13 MHz) in DMSO–d ,
6
+
13
PhCH ] , 178(8), 148(6), 127(34), 106(41), 91(100)
[
Н 5.44; N 17.05. C H N OS. Calculated, %: С 62.55;
Н5.56; N 17.16. M 326.423.
internal reference TMS. С NMR spectra were obtained
2
+
PhCH ] , 82(11), 65(16), 45(4). Found, %: С 62.45;
on a spectrometer Varian VXR-300 (125.74 MHz) from
solutions in DMSO–d6, internal reference TMS. Mass
spectra were taken on an instrument MKh-1321 (70 eV)
with a direct admission of the smple into the ion source.
The reaction pogress was monitored and the purity of
cmpounds obtained was checked by TLC on Silufol UV-
2
1
7
18
4
4-Imino-5,5-dimethyl-7-oxo-3-(furan-2-yl-methyl)-
3
6
,4,5,6,7,8-hexahydro-2Н-pyrido[3,2-е]-[1,3]thiazine-
-carbonitrile (IVb) was obtained similarly to compound
2
54 plates, eluent acetone– hexane, 3:5, development in
IVa using 0.92 ml (10 mmol) of furan-2-ylmethylamine
IIIb). Yield 1.8 g (57%), yellow powder, mp 310–312°С.
iodine vapor and under UV irradiation. Melting point
were determined on a Koeffler heating block.
(
–
1
IR spectrum, ν, cm : 3429, 3308 (NH), 2248 (C≡N),
1
Me), 1.09 (3Н, Me), 3.92 d, 3.95 d (по 1Н, NCH , J 15.0
Hz), 4.02 s (1Н, Н ), 5.15 d, 5.27 d (1Н each, SCH N,
2
1
661 (CONH). Н NMR spectrum, δ, ppm: 1.07 (3Н,
REFERENCES
2
2
6
2
1. Haijian, S., Zhongyi, W., and Haoxin, S., Chimia., 1997,
vol. 51, p. 529; Ref. Zh. Khim., 1998, 13Zh272.
2. Dotsenko, V.V., Krivokolysko, S.G., and Litvinov, V.P.,
Khim. Geteritsikl. Soedin., 2007, p. 621.
3
4
J 15.0 Hz), 6.35 s (1Н, Н of furan), 6.44 s (1Н, Н of
5
furan ), 7.63 s (1Н, Н of furan), 8.83 br.s (1Н, NH),
9
2
.
.01 br.s (1Н, NH). 13С NMR spectrum, δ, ppm: 21.61,
3.43, 36.18, 49.30, 50.90, 54.32, 60.42, 101.91, 110.01,
3. Dotsenko, V.V., Krivokolysko, S.G., and Litvinov, V.P.
Monatsh. Chem., 2007, vol. 138, p. 489.
1
11.06, 117.23, 143.75, 148.26, 171.75, 173.23, 192.47.
4
. Vatsuro, K.V. and Mishchenko, G.L., Imennye reaktsii v
organicheskoi khimii (Personal Reaction in Organic Chem-
istry), Moscow: Khimiya, 1976, p. 268.
+
Mass spectrum, m/z (I %): 318(4) [M + 2] , 317(11)
[
rel,
+
+
M + 1] , 316(58) [M] , 287(26), 235(6) [M – furan-2-
ylmethylene], 222(10), 127(29), 96(26), 81(100) [furan-
5. Dyachenko, V.D., Nikishin,A.A., and Litvinov, V.P., Khim.
Geteritsikl. Soedin., 1997, p. 996.
+
2
-ylmethylene] , 67(9), 53(27). Found, %: С 56.91;
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012