The simple N-phenyl amide of 5-amino-1,3-dimethylpyrazolecarboxylic acid II has been shown to exhibit antifungal activity [ 8 ]. The 5-aminopyrazinylcarboxamidopyrazole derivatives has been recently reported as a potent antibacterial agent with a very broad spectrum [ 12 ].
Recently, the components of the mitotic machinery have been targeted in an attempt to develop novel anticancer agents. Results and discussion The synthesis of 3-dimethylbenzoyl propenenitriles 1 a-b is the vital key intermediate for the synthesis of various nitrogen heterocycles, such as pyrazole and pyrimidine derivatives. The literature reports suggest that 1,3,4-trisubstituted pyrazole derivatives are important compounds in the preparation of 1,5-diphenylpyrazole nonnucleoside derivatives, which are used as HIV-1 nonnucleoside reverse transcriptose inhibitors [ 15 ].
Similarly, 4-cyano pyrazole derivatives showed significant biological activity by inhibiting alcohol dehydrogenase [ 16 ]. They also produce skeletal muscle relaxation on administration to animals [ 17 ]. In the literature, several methods have been reported for the synthesis of 5-amino pyrazole derivatives.
Hasseneen and coworkers [ 18 ] have prepared pyrazole derivatives by the reaction of nitrile imine with fumaronitrile. Jachak and co-workers [ 19 ] also reported the synthesis of 4-cyano pyrazole derivatives by starting with cyanoacetaldehyde, DMF-DMA N,N-Dimethylformamide dimethyl aceta and hydrazines. Recently, David Tupper [ 20 ] has reported the synthesis of 4-cyano pyrazole derivatives by starting with compounds similar to 1a. These workers have prepared 4-cyano pyrazole derivatives along with 5-amino pyrazole derivative by refluxing 3-dimethylaminobenzoylpropenenitrile 1a with phenyl hydrazine or hydrazine in ethanol.
However, the product was always a mixture of 4-cyano and 5-aminopyrazole derivatives. These workers have separated the mixture of pyrazoles by column chromatography and observed that the reaction of hydrazine or phenyl hydrazine took place with 3-dimethylaminoaroyl-propenenitrile to furnished pyrazole carbonitrile as major and aminopyrazoles as minor products. Because of this the triple bond of a nitrile accepts a nucleophile in a manner similar to a carbonyl.
Nitriles can be converted to carboxylic acid with heating in sulfuric acid. During the reaction an amide intermediate is formed. The final step of the mechanism involves the attack of the phenyl anion attacking the cyano-carbon, pushing the electron pair over to the sulfur, which readily diffuses the negative charge and is further stabilized by the potassium ion , resulting in the final benzonitrile product and potassium hydrosulfide. Applications[ edit ] Aromatic nitriles have a few applications, including polyrecombination to form polymers ,  are sometimes studied as biologically active molecules  and undergoing Ritter reactions to form amides.
A similar rationale explains why the more covalent cyanide salts such as silver cyanides and cuprous cyanides also give isonitriles as main product. As the isonitriles are rapidly hydrolyzed to amines and formic acid, an extraction step with hydrochloric acid is normally sufficient in practice to remove these impurities from a desired nitrile product.The budirol propiphenazonum is an analgesic efficacy. When protic solvents are used, the resulting greater solvation of this carbon center is thought to favor the competing reaction at the weaker nitrogen center. History[ edit ] In Hugo Schiff observed that the reaction between benzoyl chloride with potassium cyanide produced the desired benzonitrile. The R-C-N bond angle in and nitrile is o which give a nitrile functional group a linear shape. Literature reports over the past hundred years and their chemistry have been reviewed in [ 5 ] and in [ 6 ] and proved their importance in medicinal and technical applications. A similar rationale explains why the more covalent cyanide salts such as silver cyanides and cuprous cyanides also give isonitriles as main product.
Similarly, 4-cyano pyrazole derivatives showed significant biological activity by inhibiting alcohol dehydrogenase [ 16 ]. The substituted derivatives of pyrazole has been used in medicines and in other technical applications. Letts delved much deeper into the synthesis of nitriles. Mechanism 1 Nucleophilic attach on thionyl chloride 2 Leaving group removal 4 Leaving group removal Reactions of Nitriles The carbon in a nitrile is electrophilic because a resonance structure can be drawn which places a positive charge on it. HCl furnished 4-cyano pyrazole derivative 3 a-i as a single product Experiment No.
Herein, the new route for the synthesis of 4-cyano pyrazole and 5-amino pyrazole derivatives has been described. Resonating structures for pyrazole Pyrazole resistant to oxidation and reduction reaction due to loss of aromaticity, but may be hydrogenated catalytically, first to pyrazoline, and then to pyrazolidine.
Pharmacological interest Pyrazole nucleus constitutes a number of sub-structures of natural products and biologically active compounds. Substituted benzonitriles are important in many fields including pharmaceuticals. Benzonitrile is a precursor in the synthesis of Fadrozole , an aromatase inhibitor used in the treatment of breast cancer.
During the reaction an amide intermediate is formed. Section I: Synthesis of 4-cyano pyrazole derivatives, 3a-i Different methods were used for the synthesis of 4-cyano and 5-amino pyrazole derivatives.