Reaction of aliphatic imines of trimethylsilylpropinal with 8-mercaptoadenine

Article abstract of DOI:10.1134/S1070363210060241

N9-Alkyl-7-(trimethylsilyl)-9H-[1,3]-thiazino[3,2-e]purine-4,9-diamines were synthesized by reaction of 3-trimethylsilyl-2-propinal alkylimines with 8-mercaptoadenine in anhydrous DMF. DFT quantum-chemical calculations of isomeric forms of one of the reac

Full text of DOI:10.1134/S1070363210060241

ISSN 1070-3632, Russian Journal of General Chemistry, 2010, Vol. 80, No. 6, pp. 1193–1195. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © M.V. Karpov, N.S. Panina, A.V. Eremin, M.D. Stadnichuk, A.N. Belyayev, 2010, published in Zhurnal Obshchei Khimii, 2010,
Vol. 80, No. 6, pp. 1025–1027.
Reaction of Aliphatic Imines of Trimethylsilylpropinal
with 8-Mercaptoadenine
M. V. Karpov, N. S. Panina, A. V. Eremin, M. D. Stadnichuk, and A. N. Belyayev
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 198013 Russia
e-mail:mihkarpow@gmail.com
Received December 18, 2009
Abstract—N9-Alkyl-7-(trimethylsilyl)-9Н-[1,3]-thiazino[3,2-е]purine-4,9-diamines were synthesized by reac-
tion of 3-trimethylsilyl-2-propinal alkylimines with 8-mercaptoadenine in anhydrous DMF. DFT quantum-
chemical calculations of isomeric forms of one of the reaction products were performed.
DOI: 10.1134/S1070363210060241
Presently chemistry of 1-aza-1,3-enynes is one of
the intensively developing fields of organic chemistry
since purposeful synthesis of heterocyclic compounds
of different types is possible on their basis [1–5].
mercaptobenzimidazole proceeds in methanol and is
accompanied with desilylation [6]. In this work the
reaction of alkylimines of 3-trimethylsilyl-2-propinal
with 2-mercaptobenzimidazole, 8-mercaptoadenine, in
DMF was studied.
It was shown earlier that the reaction of 1-aza-1,3-
enines with 2-mercaptobenzimidazole gives rise to
polynuclear heterocyclic compounds, benzo[4,5]-
imidazole[2,1-b][1,3]thiazin-4-ols [6]. Reaction of
tert-butylimine of 3-trimethylsilyl-2-propinal with 2-
Reaction of azaenynes with 8-mercaptoadenine
proceeds in anhydrous DMF at room temperature with
small exothermal effect over ~30 min to give desired
products I–III.
H
Me3Si
NH2
N
S
N
N
R
N
+
Me3Si
HS
N
N
N
N
R
N
N
H
H2N
I_III
R = t-Bu (I); cyclo-C6H11 (II); Bn (III).
The obtained compounds I–III are crystalline
substance with high melting points (>200ºС).
Individuality of these compounds was proved by Н
protons. tert-Butyl protons appear as a singlet signal at
δH 1.04 ppm. The singlet at δH 6.83 ppm belongs to
two protons of aromatic amino group. The heterocyclic
ring proton H4 appears as a singlet signal at 8.06 ppm.
1
NMR spectroscopy.
1
The Н NMR spectrum of compound I (Fig. 1)
Compound I can exist as two possible isomers: N9-
tert-butyl-7-(trimethylsilyl)-9Н-[1,3]thiazino[3,2-е]-
purine-4,9-diamine Ia and N6-tert-butyl-8-(trimethyl-
silyl)-6Н-[1,3]thiazino[3,2-f]purine-4,6-diamine Ib
(Fig. 2). Analysis of 1H NMR spectrum of compounds
I–III testifies that all studied reactions afforded only
contains a doublet at δH 6.43 ppm with the spin–spin
coupling constant JHH 5.08 Hz (H1), a doublet at δH
2.34 ppm with JHH 8.72 Hz (H2), and a multiplet at δH
6.12–6.14 ppm (H3, thiazine ring). The singlet signal at
δH 0.29 ppm originates from nine trimethylsilyl
1193

1194
KARPOV et al.
in isomer Ia, what allows a conclusion on its greater
H2
H1
N
stability. The analysis of contributions in Еtot shows
that its electron constituent, Еel, favors isomer Ib
stabilization. However an overall decrease in Еtot in the
case of isomer Ia is achieved by smaller energy
contribution of the nuclear interaction energy Еnuc.
Therefore, the increase in nuclear repulsion energy is
one of the main factors, which destabilizes isomer Ib.
Me3Si
N
H3
S
N
N
t-Bu
H4
H4
H2
–NH2
H1
N
H2N
H3
Based on quantum-chemical calculations for com-
pound I, it is presumable that for similar compounds II
and III the most energetically favorable isomers are
those where the NH2-groups are arranged similar to the
structure of isomer Ia.
8.5 7.5 6.5 5.5 4.5 3.5 2.5
1.5 0.5
δ, ppm
Therefore, the reaction of N-alkylimines of 3-
trimethylsilyl-2-propinal with 8-mercaptoadenine in
anhydrous DMF, unlike reaction of N-tert-butylimine
of 3-trimethylsilyl-2-propinal with 2-mercaptobenz-
imidazole in methanol [6], leads to the retaining
trimethylsilyl and amine moieties in compounds I–III.
According to quantum-chemical DFT calculations, the
most probable reaction product is the isomer, where
the distance between aromatic and alkyl amino groups
is maximal.
Fig. 1. 1Н NMR spectrum of compound I.
one isomer from two possible. However, it is impos-
sible to conclude from these data, which isomer is the
most probable product.
In order to establish, which of isomers Ia or Ib has
most energetically advantageous structure, we made
quantum-chemical calculations by DFT B3LYP method
on 6-31G** basis using Jaguar 7.5 program package [7].
Analysis of normal vibration frequencies shows that
geometries of isomer structures, obtained as a result of
optimization, in gaseous phase correspond to minima on
potential energy surface. Structural parameters of isomers
Ia and Ib obtained as a result of the optimization of their
geometry are represented in Fig. 2.
EXPERIMENTAL
Analytically pure reagents and solvents were used
for the synthesis. The 1H NMR spectra were registered
on a Varian XL-300 instrument at operating frequency
300.13 MHz in DMSO-d6. Elemental analysis was
performed on a CHN-analyzer Perkin-Elmer 2400.
Calculated values of total energies of systems Еtot
attest that at small difference in energies of zero vibra-
tion level the lesser value of Еtot (by –38.9 kJ mol–1) is
N9-tret-Butyl-7-(trimethylsilyl)-9Н-[1,3]thiazino-
[3,2-е]purine-4,9-diamine (I). To 50 ml of 0.01 М
N
1.323
N
1.341
1.375
C
C
C
1.340
N
C
1.412
S
N
C
C
1.356
S
1.763
1.380
1.310
C
1.383
C
N
C 1.760
1.780
1.414
Si
1.343
N
C
1.792
C
1.903
1.342
C
C
1.408
1.340
1.396
C
C
Si
C
1.380
1.905
1.338
C
N
C
1.361
1.340
1.521
1.414
1.336
1.382
N
1.452
N
C
1.335
1.473
C
N
1.513
1.456
N
C
C
N
C
C
1.484
C
C
C
C
C
C
Ia
Ib
Fig. 2. Molecular structure and main bond lengths by DFT data for compound I.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 6 2010

REACTION OF ALIPHATIC IMINES OF TRIMETHYLSILYLPROPINAL
1195
solution of trimethylsilylpropinal imine in anhydrous
DMF was added 0.01 mol of 8-mercaptoadenine at
stirring to complete reagents dissolution. Then the
mixture was filtered. After 30 min the end product
begins to crystallize. Yellow crystals were filtered off
and dried in air. Yield 60%, mp 282°С. Found, %: С
51.6; Н 6.8; N 24.2. C15H24N6SSi. Calculated, %: С
21.9. C18H22N6SSi. Calculated, %: С 56.5; Н 5.8; N
1
21.9. Н NMR spectrum, δ, ppm: 0.29 s (9H), 3.41–
3.56 m (3H), 6.10 d (1H, 3JHН 4.36 Hz), 6.25 d (1H,
3JHН 4.36 Hz), 6.98 br. s (2H), 7.08–7.20 m (5H), 8.03
s (1H).
REFERENCES
1
51.69; Н 6.94; N 24.11. Н NMR spectrum, δ, ppm:
0.29 s (9H); 1.04 s (9H), 2.28 d (1H, 3JHН 8.72 Hz),
6.10–6.15 m (1H), 6.43 d (1H, 3JHН 5.08 Hz), 6.83 br.s
(2H), 8.06 s (1H).
1. Stadnichuk, M.D., Khramchikhin, A.V., Piterskaya, Yu.L.,
and Suvorova, I.V., Zh. Obshch. Khim., 1999, vol. 69,
no. 4, p. 616.
2. Kel’in, A.V., Sromek, A.W., and Gevorgyan, V., J. Am.
Chem. Soc., 2001, vol. 9, no. 123, p. 2074.
N9-Cyclohexyl-7-(trimethylsilyl)-9Н-[1,3]thiazino-
[3,2-е]purine-4,9-diamine (II) was prepared similarly.
Yield 55%, mp 242°С. Found, %: С 54.7; Н 6.9; N
22.5. C17H26N6Ssi. Calculated, %: С 54.51; Н 7.00; N
3. Shimizu, M., Nishi, T., and Yamamoto, A., Synlett.,
2003, no. 10, p. 1469.
4. Hachiya, I., Ogura, K., and Shimizu, M., Synthesis,
1
22.44. Н NMR spectrum, δ, ppm: 0.29 s (9H), 0.81–
2004, no. 9, p. 1349.
1.08 m (5H), 1.48–1.58 m (5H), 2.39–2.51 m (2H),
6.12 t (1H, 3JHН 11.62 Hz), 6.24 d (1H,3JHН 5.09 Hz),
7.70 s (2H), 8.04 s (1H).
5. Hachiya, I., Ogura, K., and Shimizu, M., Org. Lett.,
2002, vol. 4, no. 16, p. 2755.
6. Karpov, M.V., Khramchikhin, A.V., and Stadnichuk, M.D.,
Zh. Obshch. Khim., 2005, vol. 75, no. 9, p. 1579.
N9-Benzyl-7-(trimethylsilyl)-9Н-[1,3]thiazino-
[3,2-е]purine-4,9-diamine (III) was prepared similarly.
Yield 60%, mp 220°С. Found, %: С 56.4; Н 5.6; N
7. Jaguar, Version 7.5, Schrodinger, LLC, New York,
2008.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 80 No. 6 2010