Amine interchange of cyanothioacetamide with morpholine and synthesis of 3-amino-2-(4-acetylphenylcarbamoyl)-5-morpholinothiophene [6]

Full text of DOI:10.1023/B:RUGC.0000031876.17660.b5

Russian Journal of General Chemistry, Vol. 74, No. 4, 2004, pp. 641 642. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 4, 2004,
pp. 701 702.
Original Russian Text Copyright
2004 by Dyachenko.
LETTERS
TO THE EDITOR
Amine Interchange of Cyanothioacetamide
with Morpholine and Synthesis
of 3-Amino-2-(4-acetylphenylcarbamoyl)-5-morpholinothiophene
V. D. Dyachenko
Shevchenko Lugansk State Pedagogical University, Lugansk, Ukraine
Received July 24, 2003
There is only one published example of amine
interchange of thioacetamide with piperidine [1], as
follows from reviews [2 5]. We found that cyanothio-
acetamide I undergoes amine interchange in the reac-
tion with morpholine in ethanol at 20 C. Compound II
is formed at equimolar ratio of the reactants, and com-
pound III, at the 1 : 2 ratio. Alkylation of II with
-chloro-(4-acetyl)acetanilide in DMF in the presence
of a twofold excess of KOH yields previously un-
known 3-amino-2-(4-acetylphenylcarbamoyl)-5-mor-
pholinothiophene VII via intermediates V and VI.
The mechanisms of the reactions discovered and the
synthetic potential of new CH acids II and III and of
thiophene derivative VII as nucleophilic agent were
studied.
O
NH
O
NH
2
O
O
N
NH2
H2N
N
NH3
NC
NH3,
CH2(CN)2
NC
S
S
S
S
II
I
III
Me
O
NH
, 2KOH
Cl
O
IV
NH2
N
>C N
Me
O
Me
Me
N
N
N
N
N
N
S
S
S
O
O
O
O
O
H
O
H
O
H
O
V
VI
VII
1
1
3-Morpholino-3-thioxopropanonitrile II. Yield
cm : 3190, 3278, 3356 (NH2). H NMR spectrum,
, ppm: 3.70 m (4H, CH2NCH2), 3.91 s (2H, CH2),
4.42 m (4H, CH2OCH2), 8.87 br.s and 9.43 br.s (1H
each, NH2). Mass spectrum, m/z (Irel, %): 206 (6)
[M + 2]+, 205 (7) [M + 1]+, 204 (55) [M]+, 171 (8),
144 (9), 119 (22), 110 (20), 101 (8), 86 (100), 60
(39), 54 (18), 42 (23). Found, %: C 40.93; H 6.07; N
13.58. C7H12N2OS2. Calculated, %: C 41.15; H 5.92;
N 13.71.
1
76%, mp 89 C (from EtOH). IR spectrum, , cm :
1
2264 (C N). H NMR spectrum, , ppm: 3.70 m (6H,
CH2NCH2 and CH2CN), 4.16 m (4H, CH2OCH2).
Found, %: C 49.20; H 6.07; N 16.28. C7H10N2OS.
Calculated, %: C 49.39; H 5.92; N 16.46.
1-Amino-3-morpholino-1,3-propanedithione III.
Yield 39%, mp 143 150 C (dec.). IR spectrum,
,
1070-3632/04/7404-0641 2004 MAIK Nauka/Interperiodica

642
DYACHENKO
3-Amino-2-(4-acetylphenylcarbamoyl)-5-mor-
Kratos MS-890 mass spectrometer (70 eV). The struc-
tures of II and III were studied by single crystal X-ray
diffraction; the results will be reported later.
pholinothiophene VII. Yield 71%, mp 199 200 C
1
(from BuOH). IR spectrum, , cm : 3242, 3297,
1
3425 (NH2), 1680 (C=O), 1657 [CONH, (NH2)]. H
NMR spectrum, , ppm: 2.50 s (3H, Me), 3.17 m (4H,
CH2NCH2), 3.75 m (4H, CH2OCH2), 5.67 s (1H,
C4H), 6.68 br.s (2H, NH2), 7.80 br.s (4H, C6H4),
8.87 br.s (1H, CONH). Found, %: C 58.87; H 5.32; N
12.30. C17H19N3O3S. Calculated, %: C 59.11; H 5.54;
N 12.16.
REFERENCES
1. Micheel, F., Krzeminski, Z., Himmelmann, W., and
Kuhlkamp, A., Lieb. Ann., 1952, vol. 575, nos. 1 3,
p. 90.
2. Petrov, K.A. and Andreev, L.N., Usp. Khim., 1969,
vol. 38, no. 1, p. 41.
3. Petrov, K.A. and Andreev, L.N., Usp. Khim., 1971,
vol. 40, no. 6, p. 1015.
4. Litvinov, V.P., Usp. Khim., 1999, vol. 68, no. 9, p. 817.
5. Jagodzinski, T.S., Chem. Rev., 2003, vol. 103, no. 1,
p. 197.
The IR spectra were recorded on an IKS-40 spec-
1
trophotometer (mulls in mineral oil). The H NMR
spectra were measured on Gemini-200 (199.975 MHz,
compounds II, VII) and Bruker DR-500 (500.13 MHz,
compound III) spectrometers in DMSO-d6 (reference
TMS). The mass spectrum of III was taken on a
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004