C-phosphorylated 4,5-dihydro-thiazoles as products of the reaction of acetals of α-thio-cyanato-α-phosphorylacet-aldehydes with thioamides

Full text of DOI:10.1007/s10593-009-0341-4

Chemistry of Heterocyclic Compounds, Vol. 45, No. 7, 2009
C-PHOSPHORYLATED 4,5-DIHYDRO-
THIAZOLES AS PRODUCTS OF THE
REACTION OF ACETALS OF α-THIO-
CYANATO-α-PHOSPHORYLACET-
ALDEHYDES WITH THIOAMIDES
Kh. A. Asadov1*, S. N. Guseinova2, G. G. Mikailov2,
R. J. Valiullina1, A. M. Magerramov2, and F. I. Guseinov1
Keywords: acetals of phosphorylated α-thiocyanatoaldehydes, thioamides, C-phosphorylated
4,5-dihydro-1,3-thiazoles.
Compounds containing a thiazole ring have a broad spectrum of biological activity such as antimicrobial
[1] and anti-inflammatory properties [2]. Thus, it was of interest to use acetals of phosphorylated
α-thiocyanatoaldehydes 1 [3] as reagents in condensation with thioamides in order to synthesize thiazole
derivatives with various pharmacophoric groups.
O
H2N
R
HN
R
(EtO)2P
SCN
SH
S
+
CH(OEt)2
X
1a,b
NH
O
1
S
5
O
NH
2
S
NH
(EtO)2P
X
(EtO)2P
X
2
S
R
4
S
N 3
1 R
CH(OEt)2
4
EtO
2
3a–d
1 a X = CO2Et, b X = Ph; 3 a R = Me, X = CO2Et; b R = Ph, X = CO2Et;
c R = Me, X = Ph; d R = X = Ph
_______
* To whom correspondence should be addressed, e-mail: esedoglu@mail.ru.
1 Kazan State Technological University, Kazan 420015, Russia.
2Baku State University, Baku AZ-1148, Azerbaijan; e-mail: mikail_05@mail.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1098-1100, July, 2009. Original
article submitted November 14, 2008, submitted after revision April 20, 2009.
878
0009-3122/09/4507-0878©2009 Springer Science+Business Media, Inc.

We have shown that the reaction of acetals 1 with thioamides in acetonitrile or absolute ethanol gives
C-phosphorylated 4,5-dihydro-1,3-thiazoles 3.
The reaction probably proceeds through formation of linear intermediate 2. Attack of the proton of the
C(4) imino group at the methine carbon atom in intermediate 2 is accompanied by intramolecular cyclization to
give heterocycle 3.
The IR spectra of 3a and 3b lack the C(4)=NH absorption band at 2500-2600 cm-1 but have bands at
1070 (CH–O), 1290 (P=O), and 1635 (C=N), and 2980 cm-1 (C(2)=NH) as well as ketone group stretching
bands at 1680-1700 cm-1.
1
The H NMR spectra of compounds 3a-d lack signals for the acetal and C(4)=NH imino fragments (at
5.0-5.2 ppm with 3JPH = 2.5 Hz and 6.5-8.0 ppm, respectively). The ratio of the integral intensities of the protons
of the ethoxy fragments at the phosphorus atom and at the methine carbon atom (9:2:4) exclude structure 2. The
S–C(R)=NH proton is found in the vicinity of 4.5 ppm as a broad singlet, while the semiaminal proton at C(4)
3
appears as a double doublet (mixture of diastereomers) at 5.1-5.2 ppm with JPH = 12.5 Hz. The phenyl ring
protons appear as a series of downfield multiplets at 7.2-7.9 ppm. The 31P NMR spectrum shows signals at 15.41
and 16.47 ppm, indicating formation of a mixture of diastereomers.
1
The IR spectra for KBr pellets were taken on a UR-20 spectrometer. The H NMR spectra were taken
for solutions in acetone-d6 on a Tesla BW-567 spectrometer at 100 MHz with HMDS as the internal standard,
while the 31P NMR spectra were taken on a Bruker WP-80 spectrometer at 32.38 MHz with 85% H3PO4 as the
standard.
5-Diethoxyphosphoryl-4-ethoxy-5-ethoxycarbonyl-2-(1-imino)ethylthio-4,5-dihydrothiazole (3a). A
solution of thiocyanatoacetal 1a (3.83 g, 0.01 mol) and thioacetamide (0.75 g, 0.01 mol) in absolute
acetonitrile or ethanol (30 ml) was heated at reflux for 16 h. The solvent was removed in vacuum and 10 ml
3:1 ether–acetone was added to the resultant oil. The yellow crystalline precipitate was filtered off and dried to
give 2.31 g (56%) compound 3a; mp 124-129°C. IR spectrum, ν, cm-1: 1070 (CH–O); 1290 (P=O); 1635 (C=N);
1680 (C=O); 2980 (NH). 1H NMR spectrum, δ, ppm (J, Hz): 1.0 (12H, m, 4CH3); 2.3 (3H, s, CH3); 3.5-4.1 (8H,
3
m, 4OCH2); 5.1 (1H, d, JPH = 12.5, CHO); 7.8 (1H, br. s, NH). 31P NMR spectrum, δ, ppm: 15.41, 16.47.
Found,%: N 6.76; P 7.47; S 15.41. C14H25N2O6PS2. Calculated, %: N 6.80; P 7.52; S 15.53.
5-Diethoxyphosphoryl-4-ethoxy-5-ethoxycarbonyl-2-iminobenzylthio-4,5-dihydrothiazole (3b) was
obtained in 58% yield; mp 136-141°C. IR spectrum, ν, cm-1: 1040 (CH–O); 1290 (P=O); 1635 (C=N);
1
1590-1595 (Ph); 1700 (C=O); 2990 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.0 (9H, m, 3CH3); 2.35 (3H, s,
3
CH3); 3.4-4.2 (6H, m, 3OCH2); 5.1 (1H, d, JPH = 12.5, CHO); 7.2-7.8 (5H, m, C6H5); 7.5 (1H, br. s, NH).
31P NMR spectrum, δ, ppm: 15.41, 16.47. Found, %: N 6.56; P 7.67; S 15.46. C17H25N2O4PS2. Calculated, %:
N 6.73; P 7.45; S 15.38.
5-Diethoxyphosphoryl-4-ethoxy-2-(1-imino)ethylthio-5-phenyl-4,5-dihydrothiazole
(3c)
was
obtained in 70% yield; mp 118-121°C. IR spectrum, ν, cm-1: 1060 (CH–O); 1267 (P=O); 1635 (C=N); 1130
1
(CH–O); 2979 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.20 (12H, m, 4CH3); 3.2-4.1 (8H, m, 4OCH2); 5.1
3
(1H, d, JPH = 12.5, CHO); 7.3-7.9 (5H, m, C6H5); 9.2 (1H, br. s, NH). 31P NMR spectrum, δ, ppm: 15.36.
Found, %: N 5.76; P 6.38; S 13.44. C19H27N2O6PS2. Calculated, %: N 5.91; P 6.54; S 13.50.
5-Diethoxyphosphoryl-4-ethoxy-2-iminobenzylthio-5-phenyl-4,5-dihydrothiazole (3d) was obtained
in 75% yield; mp 112.5-114°C. IR spectrum, ν, cm-1: 1080 (CH–O); 1267 (P=O); 1635 (C=N); 1135 (CH–O);
1
2979 (NH). H NMR spectrum, δ, ppm (J, Hz): 1.20 (9H, m, 3CH3); 3.2-4.1 (6H, m, 3OCH2); 5.1 (1H, d,
3JPH = 12.5, CHO); 7.3-7.9 (10H, m, C6H5); 8.9 (1H, br. s, NH). 31P NMR spectrum, δ, ppm: 15.33. Found, %:
N 5.76; P 6.38; S 13.54. C22H27N2O4PS2. Calculated, %: N 5.86; P 6.49; S 13.39.
This work was carried out with the financial support of the Russian Basic Research Fund (Grant 07-03-00316-a)
and Russian Federation President's Grant (MK-4043.2007.3).
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