Assiut university Staff Researches SYNTHESIS , REACTIONS AND SPECTRAL CHARACTERIZATION OF NOVEL THIENOPYRAZOLE DERIVATIVES

4-Amino-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide has been synthesized by an innovative method. The aminoamide derivative was gently refluxed with chloroacetyl chloride under neat conditions followed by neutralization with sodium carbonate solution to afford the chloromethyl pyrimidinone compound. The chloromethyl pyrimidinone derivative was converted to the thiol derivative by the reaction with thiourea in ethanol. The thiol compound was alkylated with αhalocompounds such as ethyl chloroacetate, chloroacetone, phenacyl bromide and 2-chloro-4,6-dimethylnicotinonitrile to afford the corresponding S-alkylated compounds. The chemical structures of the newly synthesized compounds were elucidated on the basis of elemental and spectral analyses containing FT-IR, 1H-NMR, and mass spectroscopy.


RESULT AND DISCUSSION
0][21] All attempts to displace the chloride ion by the thiol group in the previously prepared 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4carbonitrile compound (1) by the reaction of thiourea in ethanol and with other moieties to obtain 5-mercapto-Nphenylpyrazole-4-carbonitrile (2) failed, giving the chloropyrazole carbonitrile starting material (1).The previous results forced us to search for another method to prepare the target amino thienopyrazole carboxamide compound (5).The desired results were achieved by the reaction of elemental sulfur with chloropyrazole in the presence of sodiumborohydride to give the non-isolated sulfanyl sodium salt (3) which underwent an in situ reaction with chloroacetamide to afford the pyrazole sulfanyl acetamide derivative (4).The latter compound underwent Thorpe-Zeigler cyclization on heating in ethanolic sodium ethoxide solution yielding the amino thienopyrazole carboxamide (5) (Scheme 1).The chemical structure of compound (5) was elucidated on the basis of elemental and spectral data.IR spectrum of compound (5) revealed appearance of absorption band at 3400, 3305, 3190 cm -1 due to two NH2 group. 1 H NMR spectrum showed two singlet signals at δ 2.60, 6.90 and 7.00 ppm characteristic for CH3 and NH2 groups respectively. 13C NMR spectrum displayed signals at 15.2 and 169.80 ppm attributed to CH3 and CONH2 groups respectively.

Scheme 1. Synthesis of aminoamide derivative of thienopyrazole.
Heating the amino carboxamide compound (5) with chloroacetyl chloride on a water bath under neat conditions followed by neutralization with diluted sodium carbonate solution afforded the chloromethylpyrazolothienopyrimidinone (6).The latter compound was characterized on the basis of elemental and spectral analysis.IR spectrum revealed the disappearance of absorption bands for NH2 groups in the amino amide compound (5) and appearance of a broad absorption band at 3480-3300 cm -1 for NH group. 1

Experimental
All melting points were uncorrected and recorded on a Gallen Kamp electric melting point apparatus.The elemental analyses were carried out at the Micro Analytical Center of Chemistry Department-Assiut University.
The FT-IR spectra were recorded using potassium bromide disks on a FT-IR 8201 PC Shimadzu. 1 H NMR and 13 C NMR spectra were obtained on a Bruker ( 1 H NMR: 400 and 300 MHz, 13 C NMR: 100 and 75 MHz) spectrometers in CDCl3 and DMSO-d6 using Me4Si as internal standard and chemical shifts are expressed as ppm.Mass spectra were measured on a Jeol-JMS 600 and Shimadzu Qp-2010 plus spectrometer at the Micro Analytical Center -Cairo University-Giza.

CONCLUSION
The aim of this work is to synthesize some new bifunctionally substituted thieno [2,3-c] pyrazole compounds which were subjected to react with different reagents to synthesize new heterocyclic rings fused or attached to thienopyrazole system namely: pyrimidinone and thien [2,3b]pyridinyl compounds.

N H 3 C Ph Cl CN N N H 3 C Ph SNa CN N N H 3 C Ph SCH 2 CONH 2 CN S CONH 2 NH 2 N N H 3 C Ph H 2 NCSNH 2 /EtOH S/ NaBH 4 N N H 3 C Ph SH CN (2) (4) (5) reflux EtOH ClCH 2 CONH 2 EtONa/ EtOH (1) (3) X
1he structure of compound (7) was confirmed using elemental and spectral data.IR spectrum revealed absorption bands at 3428 cm -1 characteristic of the NH group and 1655 cm -1 for CO group.1HNMR spectrum of the thiol derivative (7) in DMSO-d6 displayed singlet signals at δ: 3.70 ppm for CH2, at 1.20 ppm for SH group and at 3.90 ppm attributed to NH group.