Nitrogen-containing heterocyclic compounds and their derivatives have historically been invaluable as a source of therapeutic agents. Pyrazole, which has two nitrogen atoms and aromatic character, provides diverse functionality and stereochemical complexity in a five-membered ring structure. In the past decade, studies have reported a growing body of data on different pyrazole derivatives and their innumerable physiological and pharmacological activities. In part, such studies attempted to reveal the wide range of drug-like properties of pyrazole derivatives along with their structure–activity relationships in order to create opportunities to harness the full potentials of these compounds. Here, we summarize strategies to synthesize pyrazole derivatives and demonstrate that this class of compounds can be targeted for the discovery of new drugs and can be readily prepared owing to recent advances in synthetic medicinal chemistry.

Review: biologically active pyrazole derivatives

Metal-Free Multicomponent Syntheses of Pyridines

Coumarin heterocyclic derivatives: chemical synthesis and biological activity

Organic synthesis using clay and clay-supported catalysts

A variety of β-enamino ketones and esters have been synthesized in high to exellent yields by reacting β-dicarbonyl compounds with amines in the presence of a catalytic amount of indium tribromide. The reaction proceeds smoothly at room temperature in a short reaction time under solvent-free conditions.

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A General and Efficient Method for the Preparation of β-Enamino Ketones and Esters Catalyzed by Indium Tribromide

A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support

A mild, one-pot synthesis of 3-cyano-4-benzopyrones from 2-hydroxyacetophenones

A clean and rapid synthesis of 5-amino and 5-alkoxycarbonylpyrazoles using montomorillonite under acid free conditions

A series of 3-Benzopyranopyridinyl and pyrazolyl 1,2-benzisoxazoles (5 & 9) has been prepared from o-hydroxyarylketones (2 & 6) derived from 3-formylchromone (1). Introduction A variety of 3-substituted 1,2-benzisoxazoles have been reported to possess physiological properties such as anticonvulsant and antispasmodic activities. Recently two 3-piperidinyl substituted benzisoxazoles, namely Abaperidone Hydrochloride and Iloperidone have been reported to exhibit promising antipsychotic activities. In addition several pyrazole derivatives and benzopyranopyridines have been reported to posses diverse types of biological activities. Furthermore 3-formylchromone 1 is a very reactive intermediate because of the presence of an unsaturated keto group, a conjugated second carbonyl at C3 and a very reactive centre at C2 which allows michael addition of nucleophile with opening of the γ-pyrone ring. These properties make 1 as a versatile synthon from which a variety of o-hydroxyheteroarylketones can be readily obtained. In continuation of our work on 3-formylchromone (1) based heterocycles and in view of the biological properties associated with 1,2-benzisoxazoles, pyrazoles and benzopyranopyridines we became interested in the synthesis of 3-benzopyranopyridinyl and pyrazolylbenzisoxazoles from the intermediate o-hydroxyheteroarylketones readily obtained from 3-formylchromone 1. Results and Discussion The required starting materials 3-(2'-hydroxybenzoyl)-5H(l)-benzopyrano(4,3-b) pyridines(2) and 4-(2'-hydroxybenzoyl)-pyrazoles (6) were readily obtained from 3-formylchromone (1). Thus, reaction of chromanone with 1, gives benzopyranomethyl benzopyranone which on reaction with ammonium acetate in acetic acid or with ammonia in aqueous methonol gives hydroxybenzoylbenzopyrano pyridines (2a-r). Reaction of 1 with Phenylhydrazine gives Vol. 9, No. 4, 2003 Synthesis of some new 3-benzo pyraopyridinyl and 3-pyrazolyl 1,2-benzisoxazoles from o-hydroxy heteroarylketones derivedfrom 3-formylchromone hydroxybenzoylpyrazoles (6a-e) in good yields. The corresponding o-hydroxyketoximes 3a-q and 7a-e were obtained from o-hydroxyketones 2a-r and 6a-e by refluxing with hydroxylamine hydrochloride in ethanol. The products were characterized by IR and H NMR spectral data. The o-hydroxyketoximes 3a-q and 7a-f were subjected to cyclization in polyphosphoric acid to give the corresponding 3-heteroaryl 1,2-benzisoxazoles (5a-q) and 9a-e in good yields as crystalline solids. Some ketoximes were also converted to oxime acetates 4 & 8 and they were subjected to intramolecular displacement of acetate from the oxime acetate using sodium hydride in dimethyl formamide. The structures of products have been characterized by analytical data supported by NMR and Mass spectral data (Table 1). 8 R=COCH3 Experimental General procedure for the preparation of 3 and 7 A mixture of o-hydroxyketone (2 or 6, 0.07 mole) and hydroxylamine hydrochloride (0.015 mole) in ethanol (15 ml) was refluxed for 6 hrs. The separated solid was filtered washed with water, ethanol and dried to give the products 3 and 7. General procedure for the preparation of 5 and 9 A mixture of phosphoricacid (3.4 g) and phosphorous pentoxide (2.5 g) was stirred at 110° for 2 hrs. The ketoximes (3 or 7, 0.005 mole) were added to PPA and maintained for 1 hr at 110°. The reaction was monitored by TLC and after completion of the reaction, it was poured onto crushed ice. The separated solid was filtered and washed with water. The crude products were purified by column chromatography using silica gel (ethylacetate : hexane; 1:9) to give pure 5 and 9. General procedure for the preparation of 4 and 8. A mixture of oxime (3 or 7, 0.01 mole), acetic anhydride (0.2 mole) was refluxed for 4 hrs. It was poured into ice water. The separated solid was filtered washed with water to give 4 and 8. They were used in the next step without further purification. General procedure for the preparation of 5 and 9 via oxime acetates A mixture of oxime acetate (4 or 8, 0.021 mole) was stirred in DMF (10 ml) and NaH (1.1 g, 0.023 ml) at 40° for 4 hrs and poured into H 2 0 (200 ml). The aqueous solution was extracted with dichloro methane and the extract was washed with water and dried over Na2S04. Evaporation of the solvent gave 5 & 7. 3-(5H-Benzopyrano [4,3-b] pyridin-3-yl) benz(l,2) isoxazole (5a) (Ri = R2 = Rj=H) The o-hydroxyketoxime 3a was converted to 5a according to the general procedure for the preparation of 5 and 9 to give 5a (85%) as white crystalline solid. Melting point 216°C, M 300

D. Latha

Papers

A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support

A mild, one-pot synthesis of 3-cyano-4-benzopyrones from 2-hydroxyacetophenones

A clean and rapid synthesis of 5-amino and 5-alkoxycarbonylpyrazoles using montomorillonite under acid free conditions

SYNTHESIS OF SOME NEW 3-BENZOPYRANOPYRIDINYL AND 3-PYRAZOLYL 1,2-BENZISOXAZOLES FROM o-HYDROXYHETEROARYL KETONES DERIVED FROM 3- FORMYLCHROMONE

An efficient one step conversion of 3-formylchromones into 3-cyanochromones