Reactivity of 2-Cyano-N-(4-(1-Methyl-1H-benzo[d]imidazol-2-yl)-3-(M ethylthio)-1-Phenyl-1H-Pyrazol-5-yl)Acetamide: A Facile Synthesis of Pyrazole, Thiazole, 1,3,4-Thiadiazole and Polysubstituted Thiophene Derivatives

Treatment of 2-cyano-N-(4-(1-methyl-1H-benzo[d]imidazo l-2-y l)-3-(methylthio)-1-phenyl-1H-pyrazol-5-yl) acetamide (4) with phenyl isothiocyanate gave the thiole derivative (6) which on treatment with hydrazonyl chlorides (7a-c) furnished 1,3,4-th iadiazole derivatives (9a-c). React ion of cyanoacetamide derivative (4) with active methylene reagents such as malononitrile o r ethyl cyanoacetate and elemental sulfu r afforded the corresponding polysubstituted thiophene derivatives (18a,b). Reaction of cyanoacetamide derivative (4) with benzaldehyde yielded the phenylmethylidene derivative (21). The latter showed interesting reactivity towards cyanomethylene reagent and hydrazine derivatives afforded pyrane (22a,b) and pyrazole (25a,b) derivatives.

In add ition , ben zimid azo le h as been an imp o rtan t Pyrazol-5-yl)Acetamide: A Facile Synthesis of Pyrazole, Thiazole, 1,3,4-Thiadiazole and Polysubstituted Thiophene Derivatives derivatives of expected potential b iological activity and excellent pharmacology encouraged us to synthesis novel entitled derivatives.
The IR spectrum of (6) revealed absorption bands at 3362 cm -1 , 3215 cm -1 for the NH groups, absorption at 2206 cm -1 for the cyano function and absorption band at 1653 cm -1 for carbonyl group. Its 1 H NMR spectrum revealed the presence of two singlet signal at δ 9.85 pp m, δ 10.65 pp m assignable to the NH protons and singlet signal at δ 13.84 ppm assignable to the SH group. Its mass spectrum showed a mo lecular ion peak at m/z = 537 corresponding to a mo lecular formu la (C 28 H 23 N 7 OS 2 ).
Thus, reaction of compound (6) withC-phenyl-Nphenylhydrazonyl chloride (7a) in reflu xing ethanol solution containing triethylamine as basic catalyst afforded solely the corresponding 1,3,4-thiad iazo le derivatives (9a-c). Formation of the latter structures is assumed proceed via elimination of aniline mo lecule fro m the non-isolable intermediate (8 ) as outlined in scheme 2. The 1, 3, 4-thiadiazo le structure derivative (9a-c) was confirmed fro m the elemental analyses and spectral data of the isolated product. The IR spectrum of (9a) revealed absorption band at 2208 cm -1 assignable to cyano function and absorption band at 1662 cm -1 assignable to carbonyl group. Its 1 H NMR spectrum spectrum revealed singlet signal for NH at δ 9.98 ppm in addit ion to mult iplet signal for aro mat ic protons at δ 7.37-8.12 pp m. Its mass spectrum showed a mo lecular ion peak at m/ z = 638 corresponding to a mo lecular formu la (C 35 H 26 N 8 OS 2 ).
On the other hand we investigate the reactivity of non-isolable enaminonitrile (5) with α-halocarbonyl compounds (10a-c). These reactions may be lead to formation of either thiazole or thiophene systems or both depending on the reaction conditions and the nature of the α-halocarbonyl reagent [59]. Thus, reaction of (5) in situ with α-halo-carbonyl compounds such as bromoacetone, ethyl bromoacetate and 1-(ben zothiazo l-2-y l)-2-bro moethanone (10a-c), respectively resulted in the format ion of single product for wh ich the thiazole (12), (13 b,c) or thiophene (14) structures, can be assumed. However the elemental and spectral data of the reaction product were inco mplete accordance with the thiazo le derivatives (12) and (13b,c). The IR spectrum for (12) displayed stretching absorption band at 3347 cm -1 and 2223 cm -1 for the NH and cyano function, respectively and two carbonyl absorption band at 1685 and 1648 cm -1 . Its 1 H NM R spectrum d isplayed singlet signals at δ 10.31 pp m assignable to the NH porton and singlet signal at δ 3.73 pp m assignable to the methylene protons. The IR spectrum of (13 b) d isplayed stretching absorption band at 3218 cm -1 and 2204 cm -1 fo r the NH and cyano function. Its 1 H NM R spectrum revealed new signal at δ 1.72 pp m for methyl portons and δ 6.93 pp m assignable for thiazole =CH proton and singlet signal at δ 10.53 ppm assignable to the NH group. Its mass spectrum showed a mo lecular ion peak at m/z = 575 corresponding to a mo lecular formu la (C 31 H 25 N 7 OS 2 ).
The mass spectrum of co mpounds (12) and (13b,c) showed a molecu lar ion peak at m/ z = 577, 575 and 694 corresponding to the molecu lar formu la (C 30 H 23 N 7 O 2 S 2 ), (C 31 H 25 N 7 OS 2 ), and (C 37 unde rwent Gewald thiophene synthesis via its reaction with cyanomethylene derivatives (15a,b) and elemental sulfur in reflu xing dio xane containing triethylamine as basic catalyst afforded the 3,5-d iamino thiophene derivatives (18a,b), respectively. Formation of (18a,b) proceed via non-isolable intermediates (16) and (17). The analytical and spectral data of compounds (18a,b) are consistent with the proposed structures. The IR spectrum of (18a) displayed absorption bands at 3316, 3218 cm -1 and 2198 cm -1 for the NH 2 and cyano function and carbonyl absorption band at 1662 cm -1 . Its 1 H NMR spectrum two singlet signals at δ 4.42 pp m and δ 5.56 pp m for NH 2 protons and singlet signal at δ 10.21 ppm assignable to the NH group. Its mass spectrum showed a mo lecular ion peak at m/z = 500 corresponding to a mo lecular formu la (C 24 H 20 N 8 OS 2 ). On the other hand reaction of (4) with phenyl isothiocayanate and elemental sulfur afforded the Also, when co mpound (21) reacted with hydrazine derivatives (23a, b) afforded the 3-amino-N-

Experimental
All organic solvents were purchased fro m co mmercial sources and used as received or dried using standard procedures, unless otherwise stated. All chemical were purchased from Aldrich or Across and used without purification. Melting points were measured on a Gallen kamp apparatus and are uncorrected. IR spectra were recorded on Shimad zu FT-IR 8101 PC infrared spectrophotometer. The 1 H NM R and 13 C NM R spectra were determined in DMSO-d6 at 300 M Hz on a Varian Mercury VX 300 NMR spectrometer using TMS as an internal standard. Mass spectra were measured on a GCMS-QP1000 EX spectrometer at 70Ev. Elemental analyses were carried out at the Microanalytical Center of Cairo Un iversity. (3,5-Dimethy-1H-pyrazol-1-yl)-3-o xopropanenitrile was prepared according to the reported literature [60], Hydrazonyl halides (7a) and (7 b,c ) were prepared according to the reported literature [61] and [62,63], respectively. 4-(1-methyl-1H-benzo[d]imidazol-2-yl)-3-(methylthio)-1-P henyl-1H-pyrazo l-5-amine (3) was prepared according to the reported literature [64].