Struct Chem (2010) 21:809–816
811
–CH–), 2.18, 2.17, 2.07 (s, 9H, 39 CH3), 1.35 (t, 3H,
–CH2CH3); 13C NMR (CDCl3, ppm): d = 194.29 (t, J =
4.5 Hz, ArC=O), 168.61 (C=O, ester), 155.36 (C7=O, lac-
tam), 147.69, 147.52 (C-2 or C-5 exchangeable), 142.14,
140.96, 136.15, 129.97, 129.27, 129.18, 129.11, 128.30
(arom. carbons), 108.53 (C-4), 62.10 (C-3), 61.96 (OCH2–),
61.29 (C-3a), 21.32, 21.15, 14.53, 14.21 (49 CH3).
may produce three isomeric pyrimidine derivatives (2–4).
However, the results of TLC studies for each reaction
indicated the presence of only one product, the structures
of which were identified as ethyl 2-methyl-4-(4-meth-
ylbenzoyl)-5-(4-methylphenyl)-7-oxo-3,3a-dihydropyrazolo
[1,5-c]pyrimidine-3-carboxylate (2a) and ethyl 2-methyl-4-
(4-methylbenzoyl)-5-(4-methylphenyl)-7-thioxo-3,3a-dihyd-
ropyrazolo[1,5-c]pyrimidine-3-carboxylate (2b) (see Scheme 2).
The formation of only one of the three possible structures
is based on an X-ray study of the 7-acetyl-5-benzoyl-6-
phenyl-8-methyl-4,7-dihydropyrazolo[1,5-c]-1H-pyrimidine-
2-one [28] and the 3-acetyl-4-benzoyl-2-methyl-5-phenyl-
3,3a-dihydropyrazolo[2,3-c]-pyrimidine-7(6H)-thione [29]
thus excluding the other possible isomers.
Ethyl 2-methyl-4-(4-methylbenzoyl)-5-
(4-methylphenyl)-7-thioxo-3,3a-dihydropyrazolo
[1,5-c]pyrimidine-3-carboxylate (2b)
1-Amino-5-benzoyl-4-phenyl-1H-pyrimidine-2-thione 1b
(0.50 g), ethylacetoacetate (1.99 mL) (molar ratio 1:10
approximately) and p-toluenesulphonic acid catalyst were
homogeneously mixed. The mixture was heated at 120 °C
and kept at this temperature for 1.5 h without any solvent
in a calcium chloride guard tube fitted to a 50-mL round
bottom flask. The residue was then treated with dry diethyl
ether and filtered, and the crude product 2b was recrys-
tallized from n-butanol and allowed to dry over P2O5; yield
0.42 g (63%). M.p. 226 °C. Calc. for C25H25N3O3S
(447.55): C, 67.09; H, 5.63; N, 9.39; S, 7.16%. Found: C,
66.95; H, 5.68; N, 9.30; S, 6.93%. Selected IR data (cm-1):
t = 3186 (N–H), 3050–3010 (arom. C–H), 2974 (aliph.
C–H), 2395 (w, tautomeric S–H), 1738 (s br, C=O), 1600–
In order to make the reactions selective, we had to
determine the parameters, in other words the reaction
pathways, leading to such results. The compounds 2a,b
were obtained in moderate yields (59–63%) after evapo-
ration of the organic solvents and recrystallization from
proper solvents (like ethanol or n-butanol). All the reac-
tions were performed by heating them to 110–120 °C, by
the usual chemical methods (for details see ‘‘Experimen-
tal’’ section). A thin-layer chromatographic analysis of the
mother liquors still revealed the presence of more 2a,b and,
in cases of various reaction conditions, small amounts of
by-products (probably 3a,b or 4a,b) also were not deter-
mined. The selectivity of the reaction is controlled by the
reaction conditions and the acidity/electrophilicity balance
of the ketocarbonyl groups versus estercarbonyl groups of
EA.
1
1475 (C=C and C=N), 1230 (m, C=S). H NMR (CDCl3,
ppm): d = 8.01 (s br, 1H, NH), 7.36–6.82 (m, 8H, ArH),
5.51–5.48 (d, 1H, –CH–), 4.45–4.34 (m, 2H, –CH2CH3),
3.89–3.86 (dd, 1H, –CH–), 2.19 (s, 9H, 39 CH3), 1.36
(t, 3H, CH2CH3); 13C NMR (CDCl3, ppm): d = 193.84
(t, J = 4.6 Hz, ArC=O), 169.69 (C=O, ester), 167.77
(C=S), 160.31, 145.05 (C-2 or C-5 exchangeable), 142.59,
141.33, 135.73, 129.33, 129.25, 129.22, 129.06, 128.42
(arom. carbons), 107.88 (C-4), 62.38 (C-3), 61.89 (OCH2–
), 61.71 (C-3a), 21.36, 21.21, 14.92, 14.21 (49 CH3).
The reactions are generally initiated by the nucleophilic
attack of nitrogen atom of 1 directed onto the EA carbonyl
group. EA carbonyls’ carbons represent electrophilic sites
which can be used for the construction reaction with
nucleophiles. It should start by a nucleophilic attack of the
nitrogen atom’s lone pair electrons of 1 to the b carbonyl
carbon of EA. The cyclization of 1 to 2, via the elimination
of a water molecule, occurs by heating at 110–120 °C. In
the light of this, based on the proposed reaction pathway,
we showed in detail the reaction pathway of 1 with EA as
outlined in Scheme 3.
Results and discussion
Synthesis and structure determination
of the compounds 2
The structures obtained, pyrazolo[1,5-c]pyrimidine-
3-carboxylate derivatives 2a,b, were confirmed by inter-
1
The reactions of the compounds 1a,b with EA in boiling
toluene led to the formation of the corresponding pyraz-
olo[1,5-c]pyrimidine-3-carboxylate derivatives 2a,b as the
main products. The reaction conditions were mild and the
experimental procedure was simple. The progress of the
reactions was monitored by thin-layer chromatography
until complete consumption of the starting materials. Due
to the presence of two electrophilic sites in EA with dif-
ferent reactivity (ketocarbonyl and estercarbonyl groups)
that can react with nucleophiles, the reactions of 1 with EA
preting their IR, H and 13C NMR spectra, besides ele-
mental analyses (see ‘‘Experimental’’ section). In the first
experiment, product 2a was obtained with a yield of 59%
by treating 1a with EA and by refluxing them in 30 mL
toluene for 2 h.
In the IR spectrum of compound 2a, the C=O absorbtion
bands were found at 1740 and 1712 cm-1. Important
1
structural information about 2a was obtained from its H
1
NMR spectrum. The H NMR spectrum of 2a contained
four singlet peaks representing the methyl groups at 2.18,
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