Issue in Honor of Prof. Keith Smith ARKIVOC 2012 (vii) 228-241
In the light of the above report, and in continuation to our previous work,15-17 we report herein the synthesis of new pyrazole derivatives of potential biological activity.
Results and Discussion
5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxaldehyde (1) was utilized as a starting material. This aldehyde could be obtained from the easily accessible 3-methyl-1-phenyl-1Hpyrazol- 5(4H)-one under Vilsmeier-Haack reaction conditions.18 Treatment of 1 with hydrazine hydrate gave the corresponding hydrazone 2, which was allowed to react with phenyl
19
isothiocyanate to give the thiosemicarbazone derivative 3.
The thiazole 5 was obtained in a two-step sequence by reacting 1 with thiosemicarbazide to afford the corresponding thiosemicarbazone 4 followed by treatment with phenacyl bromide, in a similar procedure to that reported before.20 The IR spectrum of compound 4 showed absorption bands at .max = 3400, 3270 and 3150 cm-1 due to .NH2 and .NH. Its 1H NMR spectrum showed a singlet at . 11.44 ppm (NH), a singlet at . 8.27 ppm (NH2) and a singlet at . 8.09 ppm (CH=N), while the 1H NMR spectrum of 5 was characterized by a singlet at . 6.86 ppm due to the C-5 proton of the thiazole ring, and the absence of the NH2 signal shown by 4. The two-hydrogen singlet in the 1H NMR spectrum of 2 at . 5.48 (NH2) was replaced by two one-hydrogen singlets at . 9.86 and 9.15 ppm in the 1H NMR spectrum of 3 corresponding to two N-hydrogens.
H NH2
S
N
NH2 H3C
H3C CHO H3C
NH2
N
N S H2N N H
NH2NH2 N
N
N
Cl
Cl EtOH
Cl EtOH
N
NN
4 Ph 1 Ph 2 Ph
EtOH
ArCOCH2Br
PhNCS
EtOH
H
N Ar
H
HN
Ph
N
N H3C
H3C
N
N
S
S
N
N
Cl
Cl
N
N
Ph 5 Ph 3
Scheme 1
Two products were obtained when the thiosemicarbazone 3 was reacted with chloroacetic acid under different conditions. Thus, when the reaction was carried out in boiling ethanol in presence of sodium acetate, the corresponding thiazolidinone derivative 6 was produced, while
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