Utility of a pyrimidin-2-thione derivative in synthesis of new fused thiazolo[3,2-a]pyrimidines

Article abstract of DOI:10.1080/10426500802060727

A pyrimidin-2-thione derivative 2 was prepared and treated with 1,2-dibromoethane, chloroacetic acid and ethyl chloroacetate to give the alkylation products 3,4,9,5, respectively. Furthermore, the reaction of 2 with acrylonitrile and hydrazine hydrate yielded the pyrimidino[2,1-b]thiazine derivative 7, and [1,2,4]-triazolo[4,3-a]pyrimidine 8. Compound 9 was used as the key starting material for synthesis of thiazolo[3,2-a]pyrimidine and pyrano[2′,3′:4,5]thiazolo[3,2-a]pyrimidine derivatives 10-13, through the reaction with ethyl acetate, malononitrile, hydrazine hydrate, β-aroylacrylic acid, and chalcone, respectively. Treatment of compound 5 with 3,5-dibromo-2-aminobenzoic acid in refluxing butanol gave the 3,1-benzoxazinone derivative 6. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500802060727

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Phosphorus, Sulfur, and Silicon
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Utility of a Pyrimidin-2-Thione
Derivative in Synthesis of
New Fused Thiazolo[3,2-
a]pyrimidines
Mahmoud R. Mahmoud a & Manal M. El-Shahawi a
a Chemistry Department, Faculty of Science , Ain
Shams University , Cairo, Egypt
Published online: 03 Nov 2008.
To cite this article: Mahmoud R. Mahmoud & Manal M. El-Shahawi (2008) Utility of a
Pyrimidin-2-Thione Derivative in Synthesis of New Fused Thiazolo[3,2-a]pyrimidines,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:12, 3097-3108
To link to this article: http://dx.doi.org/10.1080/10426500802060727
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Phosphorus, Sulfur, and Silicon, 183:3097–3108, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802060727
Utility of a Pyrimidin-2-Thione Derivative in Synthesis
of New Fused Thiazolo[3,2-a]pyrimidines
Mahmoud R. Mahmoud and Manal M. El-Shahawi
Chemistry Department, Faculty of Science, Ain Shams University,
Cairo, Egypt
A
pyrimidin-2-thione derivative 2 was prepared and treated with 1,2-
dibromoethane, chloroacetic acid and ethyl chloroacetate to give the alkylation
products 3,4,9,5, respectively. Furthermore, the reaction of 2 with acrylonitrile and
hydrazine hydrate yielded the pyrimidino[2,1-b]thiazine derivative 7, and [1,2,4]-
triazolo[4,3-a]pyrimidine 8. Compound 9 was used as the key starting material
for synthesis of thiazolo[3,2-a]pyrimidine and pyrano[2ꢀ,3ꢀ:4,5]thiazolo[3,2-
a]pyrimidine derivatives 10–13, through the reaction with ethyl acetate, malononi-
trile, hydrazine hydrate, β-aroylacrylic acid, and chalcone, respectively. Treatment
of compound 5 with 3,5-dibromo-2-aminobenzoic acid in refluxing butanol gave the
3,1-benzoxazinone derivative 6. The structure assignment of the new compounds is
based on chemical and spectroscopic evidence.
Keywords Pyranothiazolopyrimidine; pyrimidines; thiazolopyrimidines; triazolopyrim-
idines
INTRODUCTION
Thiazolopyrimidines are of great importance in the field of medici-
nal chemistry for example as analgesics or due to their cerebral ner-
vous system1 or their antipurine activity.2 The synthesis of thiazolopy-
rimidines has already been reported in the literature.3−9 It can be
achieved by two routes, firstly by initial formation of the pyrimidine
ring followed by building the thiazole ring in the terminal step (azine
approach),10 or secondly by initial formation of the thiazole ring fol-
lowed by building the pyrimidine ring in the terminal step (azole
approach).11 According to the first route, we used 6-(4-methylphenyl)-4-
(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidin-2-thione 212 as a
precursor for the synthesis of thiazolopyrimidine derivatives.
Received 3 January 2008; accepted 16 March 2008.
Address correspondence to Manal M. El-Shahawi, Chemistry Department, Faculty of
Science, Ain Shams University, Cairo 11566, Egypt. E-mail: elshahawi31@yahoo.com
3097

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M. R. Mahmoud and M. M. El-Shahawi
RESULTS AND DISCUSSION
The title compound 2 was prepared via the reaction of ben-
zalacetophenone derivative 1 with thiourea in ethanolic potas-
sium hydroxide according to a literature method.13,14 Alkylation
of 2 with 1,2-dibromoethane in the presence of anhydrous potas-
sium carbonate in dry acetone gave a semisolid which when
triturated with methanol gave two fractions, the soluble one
(40%), which upon evaporation of solvent and purification, yielded
5-(4-methylphenyl)-7-(3,4,5-trimethoxyphenyl)tetrahydrothiazolo [3,2-
a]pyrimidine 3 and the insoluble fraction (15%) which recrystallized
to give bis-s-4-(4-methylphenyl)-6-(3,4,5-trimethoxyphenyl)pyrimidin-
2-yl]ethan-1,2-dithiol 4. Treatment of 2 with ethyl chloroacetate in the
presence of anhydrous potassium carbonate in dry acetone affords the
S-alkylated product 5. I.R spectrum of 5 displayed νC O ester at 1728
cm−1 and νC N at 1636 cm−1. In order to get an additional chemi-
cal proof for structure 5, compound 5 was allowed to react with 3,5-
dibromoanthranlic acid in n-butanol and afforded the benzoxazinone
derivative 6 (Scheme 1).
SCHEME 1

Pyrimidin-2-Thione Derivative in Synthesis of Thiazolo[3,2-a]pyrimidines 3099
Cyanoethylation of 2 with acrylonitrile in boiling pyridine afforded
pyrimidothiazine derivative 7 whose structure was confirmed by ana-
lytical and spectral data (c.f. Exp.). Moreover, on reacting 2 with hy-
drazine hydrate in boiling ethanol was recovered unchanged. When the
reaction was repeated in boiling acetic acid yielded the triazolopyrimi-
dine derivative 8a. Moreover, the reaction of 2 with hydrazine hydrate
in the presence of p-N,N-dimethylaminobenzaldehyde with drops of
acetic acid afforded the triazolopyrimidine derivative 8b (Scheme 1).
Furthermore, treatment of 2 with chloroacetic acid in the presence
acetic acid/ acetic anhydride and anhydrous sodium acetate yielded
thiazolopyrimidine derivative 9, which neither dissolved nor showed
evolution of CO2 gas with aqueous sodium carbonate solution indicating
the absence of carboxylic group but gave deep violet color with ethanolic
ferric chloride and its I.R spectrum displayed νC O at 1682 cm−1 and
νC N at 1628 cm−1 (c.f. Exp.).
The reactivity of methylene group in the 2-position for structure 9
has been investigated. Thus, the reaction of 9 with ethyl acetate in
the presence of sodium ethoxide afforded the thiazolo[3,2-a]pyrimidine
derivative 10. I.R spectrum of 10, displayed νC O at 1662−1650 cm−1
and νOH at 3400 cm−1 (br.) due to intramolecular hydrogen bond system
of the conjugated chelate (Scheme 2).
Furthermore, treatment of 9 with malononitrile in the presence of
catalytic amount of piperidine afforded pyrano[2ꢀ,3ꢀ:4,5]thiazolo[3,2-
a]pyrimidine derivative 11, whose I.R spectrum displayed only νC O
SCHEME 2

3100
M. R. Mahmoud and M. M. El-Shahawi
of unsaturated δ-lactone at 1742 cm−1and νNH2 at 3436, 3390, 3280
cm−1 and lack the νC≡N (c.f. Exp.).
Fusion of 9 with hydrazine hydrate in an oil-bath for 2 h at 160◦C
yielded a compound of M.F. C44H44N6O6S2 which identified as bis-
[5-(4-methylphenyl)-7-(3,4,5-trimethoxyphenyl)dihydrothiazolo[3,2-a]
pyrimidin-3-yl]hydrazine 12, its I.R spectrum displayed νNH at 3314,
3238 cm−1 and νC N at 1630 cm−1and lack νC O.
However, the base-catalyzed addition C-2 active methylene group of
9 to β-p-tolylacrylic acid and/or benzal-p-methylacetophenone in the
presence of sodium ethoxide and ethanol yielded the corresponding
Michael adducts followed by subsequent cyclization to give 13a,b, re-
spectively (Scheme 2).
EXPERIMENTAL
All melting points were taken on Griffin and Geory melting point ap-
paratus and are uncorrected. IR spectra were recorded on Pye-Unicam
1
SP1200 spectrophotometer using KBr Wafer technique. The H-NMR
spectra were determined on a Varian Gemini 200 MHz, using TMS as
internal standard (chemical shifts in δ-scale). EI-MS were measured
on Shimadzu-GC-MS operating at 70 eV. 13C-NMR spectra were mea-
sured on JEOL 75 MHz. Elemental analyses were carried out at the
Microanalytical unit, Faculty of Science, Ain Shams University by us-
ing Perkin-Elmer 2400 CHN Elemental Analyzer. The homogeneity of
the synthesized compounds was controlled by TLC (aluminum sheets
silica gel F254Merck). All reactions have been monitored by TLC.
1-(4-Methylphenyl)-3-(3,4,5-trimethoxyphenyl)-prop-2-en-1-
one 1
A mixture of p-methylacetophenone (1.34 g, 0.01 mol) and 3,4,5-
trimethoxybenzaldehyde (1.96 g, 0.01 mol) was stirred in ethanolic
potassium hydroxide for 2 h. The formed yellowish-white crystals were
filtered off, washed with water, dried and recrystallized from dioxane
to give 1 as yellow crystals, m.p.: 130−132◦C; yield 86%. I.R(ν cm−1):
1686 (CO, unsaturated ketone), 1616(C C); 1H-NMR (CDCl3) δ (ppm):
7.6−6.4 (m, 6H arom.), 5.9 (d,2H, J =13.2 MHz), 3.9 (s, 9H, 3OMe), 2.1
(s, 3H, Me); MS m/z(%): 312 (M+.,100), 221 (76.4), 167 (18.6), 91 (44.6);
anal. calcd. for C19H20O4 (312): C, 73.07, H, 6.41, found: C, 73.23, H,
6.33.

Pyrimidin-2-Thione Derivative in Synthesis of Thiazolo[3,2-a]pyrimidines 3101
6-(4-Methylphenyl)-4-(3,4,5-trimethoxyphenyl)-1,2,3,4-
tetrahydropyrimidin-2(H)-thione 2
2 was prepared according to the described method.13,14 Recrystallized
from ethanol to give 2 as pale yellow crystals; m.p.: 186−188◦C; yield
44%; I.R (ν cm−1): 3385−3180 (NH), 1632 (C N), 1230 (C S); 1H-NMR
(CDCl3) δ (ppm):12.3 (s, 1H, NH exchangeable with D2O), 10.7(s, 1H,
NH exchangeable with D2O), 7.9−6.9 (m, 6H arom.), 6.5 (s,1H, C5-H),
5.1(s,1H, C4-H), 3.9 (s, 6H, 2OMe), 3.8 (s, 3H, OMe), 2.3 (s,3H, Ar-Me);
MS m/z(%): 370(M+.,100), 204 (71.3), 145 (22.8), 91 (30.4); anal. calcd.
for C20H22N2O3S (370): C, 64.86, H, 5.94, N,7.57, S, 8.68, found: C,
64.42, H, 6.08, N,7.33, S, 9.00.
5-(4-Methylphenyl)-7-(3,4,5-trimethoxyphenyl)
tetrahydrothiazolo[3,2-a]pyrimidine 3 and Bis-s-[6-(4-
methylphenyl)-4-(3,4,5-trimethoxyphenyl)dihydropyrimidin-2-
yl]ethan-1,2-dithiol 4
A mixture of 2 (3.7 g, 0.01 mol), anhydrous potassium carbonate (3.5
g, 0.025 mol) and 1,2-dibromoethane (4.7 g, 0.025 mol) in 50-ml dry
acetone was refluxed on water bath for 16 h. The excess solvent was
evaporating till dryness, and then about 50 ml of water was added to
the reaction mixture and stirred for 20 min. The solid deposited was
filtered off, washed with water, dried and triturated with methanol to

3102
M. R. Mahmoud and M. M. El-Shahawi
give two fractions the soluble one which upon evaporation of solvent
gives 3 and the insoluble fraction 4.
3: yellow crystals; recrystallized from toluene; m.p.: 150−152◦C;
yield 46%; I.R (ν cm−1):1632 (C N); 1H-NMR (CDCl3) δ (ppm): 7.4−6.6
(m, 7Harom.+ C6-H), 4.1 (s, 1H), 3.9 (s, 6H, 2OMe), 3.8 (s, 3H, OMe), 3.2
(t, 2H, N-CH2-CH2, J = 4.8 MHz), 2.8 (t, 2H, S-CH2-CH2, J = 4.8MHz),
2.3 (s, 3H, Ar-Me); MS m/z(%): 396 (M+.,33.7), 370 (22.9), 230 (100), 167
(17.6), 91 (27.9); anal. calcd. for C22H24N2O3S (396): C, 66.66, H, 6.06,
N,7.07, S, 8.08, found: C, 66.45, H, 5.98, N,7.33, S, 8.00.
4: light brown crystal, recrystallized from dioxane; m.p.:256−258oC;
yield 15%; I.R (ν cm−1): 1625 (C N); 1H-NMR (DMSO-d6) δ (ppm):
8.1−6.7 (m, 14Harom.), 3.9−3.8 (br. s, 18H, 6OMe), 3.4 (br. s, 4H, CH2-
CH2), 2.3(s, 6H, Ar-CH3); anal. calcd. for C42H42N4O6S2 (762): C, 66.14,
H, 5.51, N,7.35, S, 8.39, found: C, 66.50, H, 5.88, N,7.07, S, 8.16.
2-Ethoxycarbonylmethylthio-6-(4-methylphenyl)-4-(3,4,5-
trimethoxyphenyl)pyrimidine 5
A mixture of 2 (3.7 g, 0.01 mol), anhydrous potassium carbonate (2.7 g,
0.02 mol) and ethylchloroacetate (1.85 g, 0.015) in dry acetone (50 ml)
was refluxed on a water bath for 12 h. The excess solvent was removed
and the reaction mixture was poured onto ice-water and stirred for
about 30 min. The solid deposited was filtered off, washed with water,
dried, and recrystallized from benzene to give 5 as colorless crystals;
m.p.: 136−138oC; yield 27%; I.R (ν cm−1): 1728(C O, ester), 1636(C N);
1H-NMR (CDCl3)δ (ppm): 8.4−7 (m, 7H arom.), 4.2 (s, 2H, SCH2CO),

Pyrimidin-2-Thione Derivative in Synthesis of Thiazolo[3,2-a]pyrimidines 3103
4.1(q, 2H, COOCH2CH3), 3.8 (s, 9H, 3OMe), 1.3 (t,3H,COOCH2CH3);
MS m/z(%): 455 (M+.+1,17.9), 410 (32.9), 382 (13.7), 288 (21.6), 181
(20.3),91 (33.4); anal. calcd. for C24H26N2O5S (454): C, 63.43, H, 5.72,
N,6.16, S, 7.05, found: C, 63.14, H, 5.38, N,5.76, S, 6.81.
2-[6-(3,4,5-Trimethoxyphenyl)-4-(4-methylphenyl)pyrimidin-2-
yl]thiomethyl-6,8-dibromo-3,1-benzoxazin-4(H)-one 6
A mixture of 5 (2.3 g, 0.005 mol), 3,5-dibromoanthranlic acid (1.5 g,
0.005 mol) and n-butanol (20 ml) was heated under reflux for 24 h.
The excess solvent was removed under reduced pressure, and the
solid deposited was triturated with diethyl ether, filtered off, dried,
and recrystallized from benzene to give 6 as yellow crystals; m.p.:
120−122◦C; yield 37%; I.R(ν cm−1): br. 1773, 1723(C O), 1680 (C N);
1H-NMR(CDCl3)δ (ppm): 8.5−6.8 (m, 9H arom.), 4.1 (s,2H, SCH2-), 3.9
(br. s, 9H, 3OMe), 2.2 (s, 3H, Ar-Me); MS m/z (%): 685 (M+.+2,70.3),
683 (M+.100), 525 (M+.-2Br,17.9), 317 (22.8), 91 (40.2); anal. calcd. for
C29H23 Br2N3O5S (683): C, 50.95, H, 3.36, N,6.15, S, 4.68, Br, 23.13,
found: C, 51.33, H, 3.71, N,6.0, S, 4.33, Br, 23.48.
4-Imino-6-(4-methylphenyl)-8-(3,4,5-trimethoxyphenyl)
dihydropyrimido[2,1-b]4H-thiazine 7
A solution of 2 (3.7 g, 0.01 mol) and acrylonitrile (0.02 mol) in pyri-
dine (20 ml) was refluxed for 6 hrs. The reaction mixture was poured
onto ice-cold water and acidified with dilute hydrochloric acid (20 ml,
pH = 4), the precipitated product was filtered off, washed with water,
dried and recrystallized from dioxane to give 7 as pale yellow crystals;
m.p.: 166−168◦C; yield 32%; I.R (ν cm−1): 3330 (NH), 1642 (C N); MS
m/z(%): 421 (M+.,100), 394 (M+.−HCN,12.8), 255 (33.2), 91 (22.7); anal.
calcd. for C23H23N3O3S (421): C, 65.55, H, 5.46, N,9.97, S, 7.60, found:
C, 65.39, H, 5.18, N,10.31, S, 7.44.

3104
M. R. Mahmoud and M. M. El-Shahawi
3-Methyl-5-(4-methylphenyl)-7-(3,4,5-trimethoxyphenyl)
dihydro-[1,2,4]-triazolo[4,3-a] Pyrimidine 8a
A mixture of 2 (3.7 g, 0.01 mol), hydrazine hydrate (0.02 mol, 80%)
in acetic acid (20 ml) was refluxed for 3 h. The H2S was liberated
during the reaction conditions. The reaction mixture was allowed to cool
and the obtained solid was filtered off, washed with water, dried and
recrystallized from acetic acid to give 8a as pale yellow crystals; m.p.:
210−212oC; yield 59%; I.R (ν cm−1): 3210 (NH), 1628 (C N); 1H-NMR
(DMSO-d6) δ (ppm):8.1(s, 1H, exchangeable with D2O), 7.8−6.8(m, 7H
arom.+ C6-H), 5.1(s,1H), 3.9(s, 9H, 3OMe),2.4 (s, 3H,C3-Me), 2.2 (s, 3H,
Ar-Me); MS m/z (%): 391 (M+. −1, 100), 226 (38.8), 91 (40.7); anal. calcd.
for C22H24N4O3 (392): C, 67.34, H, 6.12, N, 14.28, found: C, 69.86, H,
6.0, N,13.77.
3-Dimethylaminophenyl-5-(4-methylphenyl)-7-(3,4,5-
trimethoxyphenyl)dihydro-[1,2,4] -triazolo[4,3-a] Pyrimidine 8b
A mixture of 2 (3.7 g, 0.01 mol), hydrazine hydrate (0.02 mol, 80%),
ethanol (20 ml), p-N,N-dimethylaminobenzaldehyde (0.01 mol) and
drops of acetic acid was refluxed for 10 hrs. Evaporation of the excess
solvent left a yellow solid product which recrystallized from ethanol to
give 8b as yellow crystals; m.p.: 270−272oC; yield 33%; I.R (ν cm−1):
1
3310, 3240 (NH), 1646(C N); H-NMR (CDCl3) δ (ppm):7.9(s, 1H, ex-
changeable with D2O), 8.6−6.7 (m, 11H arom.+ C6-H), 4.5 (s,1H), 3.9 (s,
9H, 3OMe), 3.1 (s, 6H, NMe2), 2.3 (s, 3H, Ar-Me); MS m/z(%): 377 (M+.-
Arꢀ, 17.8), 330 (22.1), 121 (100), 91 (40.7); anal. calcd. for C29H31N5O3
(497): C,70.02, H, 6.23, N,14.08, found: C, 69.66, H, 5.92, N,13.98.

Pyrimidin-2-Thione Derivative in Synthesis of Thiazolo[3,2-a]pyrimidines 3105
7-(3,4,5-Trimethoxyphenyl)-5-(4-methylphenyl)-3-oxo-
tetrahydrothiazolo[3,2-a] Pyrimidine 9
A mixture of 2 (1.85 g, 0.005 mol), chloroacetatic acid (0.5 g, 0.005
mol) and anhydrous sodium acetate (2 g, 0.02 mol) in acetic acid (10
ml) and acetic anhydride (5 ml) was refluxed for 6 h. The reaction
mixture was allowed to cool and then poured onto water, stirred for
1 h and left overnight. The deposited solid was filtered off, dried and
recrystallized from light petroleum ether (b.p. 80−100◦C ) to give 9
as yellow crystals; m.p.: 92−94◦C; yield 65%; I.R(ν cm−1): 1682(C O),
1628(C N); 1H-NMR (CDCl3)δ (ppm): 8.3−6.8 (m, 6H arom.), 4.8 (s,1H),
3.9 (s, 9H, 3OMe), 3.7 (s, 2H, SCH2CO), 2.3 (s, 3H, Ar-Me); MS m/z(%):
410 (M+.,17.8), 370 (39.4), 244 (12.6), 181(20.3), 91(100); anal. calcd. for
C22H22N2O4S (410): C, 64.39, H, 5.36, N,6.83, S, 7.80, found: C, 64.06,
H, 4.88, N,6.71, S, 7.38.
2-Acetyl-5-(4-methylphenyl)-3-oxo-7-(3,4,5-
trimethoxyphenyl)dihydrothiazolo[3,2-a] Pyrimidine 10
A mixture of 9 (1.23 g, 0.003 mol), ethyl acetate (20 ml) in sodium
ethoxide (0.5 g sodium, 20 ml absolute ethanol) was refluxed for 6 h.
The cold reaction mixture poured onto ice-cold water and acidified with
dilute hydrochloric acid (20 ml, pH = 4). The precipitated product was
filtered off, washed with water, dried, and recrystallized from ethanol
to give 10 as pale yellow crystals; m.p.: 196−198◦C; yield 29%; I.R (ν
cm−1): br. 3400 (OH), 1662, 1650 (CO);1H-NMR (CDCl3)δ (ppm): 7.5−6.7
(m, 7H arom.+ C6-H), 5.4(s,1H), 4.3 (s,1H, C2-H), 3.8(s, 9H, 3OMe), 2.3
(s, 3H, Ar-Me), 2.1 (s, 3H, COMe); MS m/z (%): 437 (M+.-Me,30.1), 285
(22.6), 181 (19.3), 91 (100); anal. calcd. for C24H24N2O5S(452): C, 63.71,
H, 5.31, N,6.19, S, 7.08, found: C, 63.29, H, 5.09, N,6.32, S, 6.76.

3106
M. R. Mahmoud and M. M. El-Shahawi
4-Amino-8-(3,4,5-trimethoxyphenyl)-10-(4-methylphenyl)-6H-
pyrano[2ꢀ,3ꢀ:4,5]dihydrothiazolo[3,2-a]pyrimidin-2(H)-one 11
A mixture of 9 (4.1 g, 0.01 mol), malononitrile (1.98 g, 0.03 mol) and
piperidine (1 ml) in ethanol (50 ml) was heated under reflux for 8 h. The
excess solvent was removed, and the reaction mixture was poured onto
ice-cold water and acidified with dilute acetic acid. The precipitated
product was filtered off, washed with water, dried, and recrystallized
from dioxane to give 11 as yellow crystals; m.p.: 205−207◦C; yield 42%;
I.R (ν cm−1): 3390, 3280, 3172 (NH2), 1742 (CO);1H-NMR(DMSO-d6)δ
(ppm): 7.4−6.6 (m, 7H arom.+ C8-H), 5.12 (br. s,2H), 4.7 (br. s,2H,
NH2exchangeable with D2O), 3.9 (s, 9H, 3OMe), 2.34 (s, 3H, Ar-Me);
MS m/z(%): 477 (M+.,100), 433 (32.7), 310 (17.9), 168 (12.3), 91(33.3);
anal. calcd. for C25H23N3O5S(477): C, 62.89, H, 4.82, N,8.80, S, 6.70,
found: C, 63.08, H, 4.82, N,9.13, S, 6.52.
Symmetrical Bis-3-[5-(4-methylphenyl)-7-(3,4,5-
trimethoxyphenyl)dihydrothiazolo[3,2-a]pyrimidin-3-yl]
hydrazine 12
A mixture of 9 (4.1 g, 0.01 mol) and hydrazine hydrate (0.02 mol, 80%)
was fused in an oil-bath for 2 h at 160◦C. The cooled reaction mixture
was triturated with methanol to give light brown solid which filtered
off, dried, and recrystallized from dioxane to give 12 as light brown
crystals; m.p.: 218−220oC; yield 18%; I.R (ν cm−1): 3238, 3314 (NH),
1630 (C N);1H-NMR (DMSO-d6) δ (ppm): 7.4−6.8 (m, 14H arom.+ C6-
H), 6.6(br. s,2H, C2-H), 5.1 (br. s, 2H), 3.9 (s, 9H, 3OMe), 3.8(s, 9H,
3OMe), 3.1 (br. s, 2H, 2NH exchangeable with D2O), 2.2 (s, 6H, 2Ar-
Me); anal. calcd. for C44H44N6O6S2(816): C, 64.7, H, 5.39, N,10.29, S,
7.84, found: C, 65.1, H,5.0, N,10.84, S, 7.36.
2,10-di-(4-methylphenyl)-8-(3,4,5-trimethoxyphenyl)4H,6H-
pyrano[2ꢀ,3ꢀ:4,5]thiazolo [3,2-a]pyrimidine-4-carboxylic
Acid 13a
A mixture of 9 (4.1 g, 0.01 mol), β-p-tolylacrylic acid (1.62 g, 0.01 mol),
sodium ethoxide (0.5 g sodium, 20 ml absolute ethanol) and ethanol
(30 ml) was heated under reflux for 4 h. The excess solvent was re-
moved and the residual poured onto ice-cold water and acidified with
dilute hydrochloric acid (20 ml, pH = 4) to give semisolid product
which was extracted with diethyl ether .The ethereal layer treated
with aqueous sodium carbonate solution (10%). The aqueous layer sep-
arated and acidified with cold dilute hydrochloric acid. The deposited

Pyrimidin-2-Thione Derivative in Synthesis of Thiazolo[3,2-a]pyrimidines 3107
solid was filtered off, washed with water, dried, and recrystallized from
methanol to give 13a as yellow crystals; m.p.: 242−244oC; yield 35%;
I.R (ν cm−1): br. centered at 3432(OH), 1705(C O acid), 1627(C N);1H-
NMR(DMSO-d6)δ (ppm): 11.8(br. s, 1H, COOH exchangeable with D2O),
8.1−6.6(m, 11H arom.), 5.9 (br. s, 2H), 4.6(s,1H, C3-H), 3.8(s, 9H, 3OMe),
2.4 (s, 3H,Me), 2.3(s, 3H, Me); anal. calcd. for C33H30N2O6S(582):
C,68.04, H, 5.15, N,4.81 S, 5.49, found: C, 67.72, H, 5.33, N,5.10, S,
5.09.
2,10-Di-(4-methylphenyl)-4-phenyl-8-(3,4,5-trimethoxyphenyl)
4H,6H-pyrano[2ꢀ,3ꢀ:4,5] thiazolo[3,2-a]pyrimidine 13b
A mixture of 9 (4.1 g, 0.01 mol), benzal p-methylacetophenone (2.22 g,
0.01 mol), sodium ethoxide (0.5 g sodium, 20 ml absolute ethanol) and
ethanol (30 ml) was heated under reflux for 6 h and left overnight. The
reaction mixture poured onto ice-cold water and acidified with dilute
hydrochloric acid (20 ml, pH = 4). The precipitated product was filtered
off, washed with water, dried, and recrystallized from ethanol to give
13b as colorless crystals; m.p.: 196−198◦C; yield 52%; I.R (ν cm−1):
1628(C N);1H-NMR(CDCl3)δ (ppm): 7.5−6.9 (m, 15H arom.), 6.7 (s,
1H, C9-H), 4.9 (s,1H, C3-H), 4.4 (br. s, 2H), 3.9 (s, 9H, 3OMe), 2.4−2.3
(br. s, 6H, Ar-Me); anal. calcd. for C38H34N2O4S (614): C, 74.26, H, 5.53,
N,4.56, S, 5.21, found: C, 74.09, H, 5.13, N,4.98, S, 5.23.
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