New method for the synthesis of thieno[2,3-d]pyrimidines

Article abstract of DOI:10.1007/s10593-005-0083-x

The reaction of 5-formyl-4-thiocyanatopyrimidines with nitromethane was studied under various conditions. The reaction was found unexpectedly to proceed with closure of a thiophene ring to give thieno[2,3-d]pyrimidines. The use of ammonium acetate as the catalyst leads to a side reaction involving closure of an isothiazole ring to give isothiazolo[5,4-d]pyrimidines. X-ray diffraction crystallographic analysis was used to confirm the structure of thieno[2,3-d]pyrimidine.

Full text of DOI:10.1007/s10593-005-0083-x

Chemistry of Heterocyclic Compounds, Vol. 40, No. 11, 2004
NOVEL CYCLOCONDENSATION OF
2-ACYLETHYNYL-1-AMINO- AND
2-ALKOXYCARBONYLETHYNYL-1-AMINO-
ANTHRAQUINONES WITH PYRIDINES
I. I. Barabanov
Keywords: 2-acylethynyl-1-aminoanthraquinones, 2-alkoxycarbonylethynyl-1-aminoanthraquinones,
substituted 5,6,9,14,15,15a-hexahydropyrido[2,1-b]quinazoline-9,14-diones, pyridine and its derivatives,
cyclocondensation.
Acetylene derivatives of quinones are a promising group of key intermediates in the synthesis of various
condensed heterocyclic quinoid systems [1]. In many cases, heterocyclization of these compounds is achieved by
preliminary addition of N-nucleophilic reagents (secondary or primary amines, hydrazine) at the triple bond,
followed by cyclization of the adducts. Continuing research in this direction, we have established the possibility
of cyclocondensation of some acetylenyl quinones when treated with such nitrogen-containing nucleophiles as
azines.
We have found that 1-amino-2-benzoylethynylanthraquinone
1
and the ethyl ester of
(1-aminoanthraquinon-2-yl)propiolic acid (2), when dissolved in pyridine and its derivatives, react with the latter
to form substituted 5,6,9,14,15,15a-hexahydropyrido[2,1-b]quinazoline-9,14-diones 3a-d.
R1
O
O
NH2
1
N
R
O
H
C
C
C
O
O
N
N
R
O
R
C
C
H
1, 2
3a–d
1
1
1
1
,
C
CH2
1 R = Ph; 2 R = OEt,
3a–c R = Ph; a R = H, b R = Me, c R =
d R = OEt, R = H
H
Cyclocondensation of compounds 1, 2 takes 4-15 h at 35°C. The yields of compounds 3a-d are as high
as 90%. According to TLC monitoring, conversion of 1, 2 to 3a-d is not accompanied by accumulation of any
intermediates in the reaction mass. An attempt to carry out this reaction in the benzene series was unsuccessful.
__________________________________________________________________________________________
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
Novosibirsk 630090; e-mail: shvarts@kinetics.nsc.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
No. 11, pp. 1729-1731, November, 2004. Original article submitted April 23, 2004.
0009-3122/04/4011-1497©2004 Springer Science+Business Media, Inc.
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Thus ortho-benzoylethylaniline did not react with pyridine at 20°C over a period of several days even with brief
heating to the boiling point.
1H NMR spectra of the synthesized compounds were recorded on a Bruker DPX-200 (200 MHz)
spectrometer in CDCl3.
Synthesis of Compounds 3a-d (General Procedure). A solution of quinone 1 or 2 in pyridine or its
derivative was stirred at 35°C and diluted with excess water or hexane. The product (dark violet crystals) was
filtered out and recrystallized from a mixture of benzene or CHCl3 with hexane.
6-Benzoylmethylene-5,6,9,14,15,15a-hexahydropyrido[2,1-b]quinazoline-9,14-dione
(3a)
was
obtained by reaction of quinone 1 (0.14 g, 0.40 mmol) with pyridine (5.0 ml) for 6.5 h. Compound 3a (0.14 g,
1
82%) was isolated; mp >100°C (decomposes). H NMR spectrum, δ, ppm (J, Hz): H-1-4, 14a: 5.15-5.30 (1H,
m), 5.55-5.75 (2H, m), 6.17 (1H, d, J = 7.6), 6.25-6.40 (1H, m); 6.66 (1H, s, =CH); 7.40-7.60 (3H, m, m- and
p-C6H5); 7.73 (1H, d, J = 8.3, H-6(7)); 7.70-7.85 (2H, m, H-10,11); 7.95-8.05 (2H, m, o-C6H5); 8.16 (1H, d,
J = 8.3, H-7(6)); 8.20-8.35 (2H, m, H-9,12); 9.38 (1H, br. s, NH). Found, %: C 77.83; H 4.21; N 6.40.
C28H18N2O3. Calculated, %: C 78.13; H 4.21; N 6.51.
6-Benzoylmethylene-2-methyl-5,6,9,14,15,15a-hexahydropyrido[2,1-b]quinazoline-9,14-dione (3b)
was obtained by reaction of quinone 1 (0.14 g, 0.40 mmol) with γ-picoline (5.0 ml) for 4 h. Compound 3b
1
(0.13 g, 74%) was isolated; mp >100°C (decomposes). H NMR spectrum, δ, ppm (J, Hz): 1.91 (3H, s, CH3);
H-1,3,4,14a: 5.05-5.15 (1H, m), 5.35-5.60 (2H, m), 6.14 (1H, d, J = 7.7); 6.65 (1H, s, =CH); 7.35-7.55 (3H, m,
m- and p-C6H5); 7.74 (1H, d, J = 8.3, H-6(7)); 7.70-7.85 (2H, m, H-10,11); 7.95-8.05 (2H, m, o-C6H5); 8.16 (1H,
d, J = 8.3, H-7(6)); 8.20-8.35 (2H, m, H-9,12); 9.34 (1H, br. s, NH). Found, %: C 78.18; H 4.57; N 6.26.
C29H20N2O3. Calculated, %: C 78.36; H 4.54; N 6.30.
6-Benzoylmethylene-2-vinyl-5,6,9,14,15,15a-hexahydropyrido[2,1-b]quinazoline-9,14-dione
(3c)
was obtained by reaction of quinone 1 (0.10 g, 0.28 mmol) with 4-vinylpyridine (6.5 ml) for 5 h. Compound 3c
(0.11 g, 85%) was isolated; mp >100°C (decomposes). 1H NMR spectrum, δ, ppm (J, Hz): 1,3,4,14a-H, 2-vinyl:
5.30 (1H, d, J = 10.8), 5.45-5.70 (4H, m), 6.20-6.50 (2H, m); 6.69 (1H, s, =CH); 7.40-7.60 (3H, m, m- and
p-C6H5); 7.74 (1H, d, J = 8.3, H-6 (7)); 7.75-7.85 (2H, m, H-10,11); 7.95-8.10 (2H, m, o-C6H5); 8.18 (1H, d,
J = 8.3, H-7(6)); 8.20-8.35 (2H, m, H-9,12); 9.40 (1H, br. s, NH). Found, %: C 78.58; H 4.46; N 5.91.
C30H20N2O3. Calculated, %: C 78.93; H 4.42; N 6.14.
6-(Ethoxycarbonyl)methylene-5,6,9,14,15,15a-hexahydro[2,1-b]quinazoline-9,14-dione (3d) was
obtained by reaction of compound 2 (0.15 g, 0.47 mmol) with pyridine (4.7 ml) for 15 h. Compound 3d (0.16 g,
86%) was isolated. Compound 3d was characterized as a complex with benzene of composition
1
C24H18N2O4·0.5C6H6; mp 130-132°C (decomposes) (benzene–hexane). H NMR spectrum, δ, ppm (J, Hz): 1.30
(3H, t, J = 7.1, CH3); 4.05-4.35 (2H, m, OCH2 cis- and trans-isomers); H-1-4,14a: 5.10-5.20 (1H, m), 5.50-5.70
(2H, m), 6.16 (1H, d, J = 7.3), 6.25-6.40 (1H, m); 5.76 (1H, s, =CH); 7.35 (3H, s, benzene); 7.68 (1H, d, J = 8.3,
H-6(7)); 7.70-7.85 (2H, m, H-10,11); 8.03 (1H, d, J = 8.3, H-7(6)); 8.20-8.30 (2H, m, H-9,12); 9.31 (1H, br. s,
NH). Found, %: C 74.08; H 4.71; N 6.52. C27H21N2O4. Calculated, %: C 74.13; H 4.84; N 6.40.
REFERENCES
1.
M. S. Shvartsberg, I. I. Barabanov, and L. G. Fedenok, Usp. Khim. 73, 171 (2004).
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