Hamad M. Al-Matar

Green one pot solvent-free synthesis of pyrano[2,3-c]-pyrazoles and pyrazolo[1,5-a]pyrimidines.

Pyrano[2,3-c]pyrazoles are obtained via mixing ethyl acetoacetate, hydrazine hydrate, aldehydes or ketones and malononitrile in the absence of solvent. These same products were also obtained by reacting arylidenemalononitriles 3 with 3-methyl-2-pyrazolin-5-ones. NOE difference experiments confirmed that these products exist solely in the 2H form. Similar treatments of 3-amino-2-pyrazolin-5-one with arylidene-malononitrile afforded adduct 6. Similarly mixing ethyl cyanoacetate, hydrazine hydrate, aldehydes, with malononitrile gave the same product 6. A novel synthesis of 4-oxo-4H-pyrano[2,3-c]pyrazole (8) could be achieved via reacting 3-methyl-2-pyrazolin-5-one with a mixture of cyanoacetic acid and acetic anhydride. Similar treatment of 3-aminopyrazole 11 with the benzylidene-malononitrile produced the pyrazolo[2,3-a]pyrimidines 12a,b.

Chitosan Based Heterogeneous Catalyses: Chitosan-Grafted-Poly(4-Vinylpyridne) as an Efficient Catalyst for Michael Additions and Alkylpyridazinyl Carbonitrile Oxidation

Chitosan-grafted-poly(4-vinylpyridine) (Cs-PVP) copolymers could be synthesized under heterogeneous conditions in presence of a potassium persulfate and sodium sulfite redox system. The synthesized graft copolymer could be utilized effectively, in the form of beads, as an efficient catalyst for Michael additions of active methylenes to functionally substituted alkenes. Moreover, methyl moiety oxidation in methyl pyridazinyl carbonitriles by H2O2 in the presence of chitosan-g-polyvinyl pyridine–supported iron (III) complex, Cs-PVP/Fe, could be affected. A variety of pyrans, naphthopyrans, and thiopyrans could be synthesized efficiently in the presence of these graft copolymer beads by novel catalytic routes. These polymeric catalysts could be used instead of the old toxic commercial organic basic catalysts, piperidine or pyridine, and could be readily isolated from the reaction mixture and recycled several times without significant loss of catalytic activity.

Studies on 3-Oxoalkanenitriles: Novel Rearrangement Reactions Observed in Studies of the Chemistry of 3-Heteroaroyl-3-Oxoalkanenitriles as Novel Routes to 2-Dialkylaminopyridines

3-Aroyl and 3-heteroaroyl substituted 3-oxoalkanenitriles were synthesized by the reactions of activated aromatic and hetero-aromatic substances with cyanoacetic acid in the presence of acetic anhydride. As part of studies focusing on the preparation of cyanoacetyl-1-N-methylbenzimidazole, we observed that reaction of N-methyl-benzimidazole with the cyanoanhydride formed by condensation of cyanoacetic acid with acetic anhydride, leads to the formation of 2-(1,3-diacetyl-2,3-dihydro-1H-benzo[d]-imidazol-2-yl)acetonitrile (5), whose structure was confirmed by X-ray crystallographic analysis. 3-Oxoalkanenitriles 3a,b were observed to undergo condensation reactions with dimethylformamide dimethyl acetal (DMFDMA) to afford the corresponding enamino-nitriles, which react with malononitrile to give 2-dialkylaminopyridines through a pathway involving a new, unexpected rearrangement process. Reactions of 3-oxoalkanenitriles with ethyl acetoacetate were found to afford 2-oxopyran-3-carbonitriles, also occurring via this unexpected rearrangement process. Mechanisms to account for both rearrangement reactions are suggested. In addition, reactions of 3-oxoalkanenitriles with acetylacetone in acetic acid in the presence of ammonium acetate result in the formation of pyridine-3-carbonitriles. Finally, upon heating in the presence of zeolite 3-oxoalkanenitriles 3b,c self-trimerized to produce the corresponding aniline derivatives 23b,c.

Studies with beta-oxoalkanonitriles: simple novel synthesis of 3-[2,6-diaryl-4- pyridyl]-3-oxopropanenitriles.

Heteroaromatization of ethyl 2-cyano-4-oxo-2-(2-oxo-2-arylethyl)-4-aryl-butanoates 3a,b with ammonium acetate gave ethyl 2,6-diarylisonicotinates 4a,b.Treatment of the latter with acetonitrile afforded novel β-oxoalkanonitriles 6a,b. Reactions of 6a,b with phenyl hydrazine and hydroxylamine gave the corresponding pyridyl aminopyrazoles 8a,b and pyridyl aminoisoxazoles 10a,b, respectively.

Efficient Routes to Pyrazolo[3,4-e][1,2,4]triazines and a New Ring System: [1,2,4]Triazino[5,6-d][1,2,3]triazines

Arylhydrazonomalononitriles 1a,b react with phenylhydrazine to yield amidrazones 2a,b that cyclize to give 2-aryl-5-phenylhydrazono-2,5-dihydro-[1,2,4]-triazine-6-carbonitriles 5a,b upon reaction with dimethylformamide dimethylacetal (DMFDMA). Refluxing 5a,b in glacial acetic acid resulted in the formation of the pyrazolo-1,2,4-triazines 6a,b. Compounds 6a,b were also formed upon treatment of 3-amino-4-phenylhydrazono-1-phenyl-2-pyrazolin-5-ones 7a,b with DMFDMA. Reacting these triazinyl arylhydrazononitriles 5a,b with hydroxylamine hydrochloride in ethanolic sodium acetate afforded amidrazones 8a,b that are readily cyclized in refluxing dimethylformamide into [1,2,4]triazino[1,2,3]triazines 10a,b.

Alkylheteroaromatic-carbonitriles as building blocks in heterocyclic synthesis: synthesis of ethyl 1-substituted-5-cyano-4-methyl-6-oxopyridine-3-carboxylates: versatile precursors for polyfunctionally substituted isoquinolines and pyrido pyridine

The title compounds were prepared via reacting diethyl 2-cyano-4-dimethylamino-methylene-3-methylpent-2-enedioic acid 2 with hydrazine hydrate and with ethyl amine. The formed pyridones 3a condensed with dimethylformamide dimethyl acetal to yield the corresponding enamine 4 that could be cyclised into the pyrido[3,4-c]pyridine 5 by reflux in acetic acid in presence of ammonium acetate. The reaction of 3a with elemental sulfur afforded the thienopyridine 6 that reacted readily with electron poor olefins and acetylenes to yield isoquinolines 8, 10 and 11. Compound 3a reacted with benzylidene-malononitrile to yield the isoquinoline 14.

Studies on 2-arylhydrazononitriles: synthesis of 3-aryl-2-arylhydrazopropanenitriles and their utility as precursors to 2-substituted indoles, 2-substituted-1,2,3-triazoles, and 1-substituted pyrazolo[4,3-d]pyrimidines.

Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl2 in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully used as valuable precursors to synthesize 1,2,4-oxadiazolylindoles 8a,b. The reaction of arylhydrazononitriles 4a,b with hydroxylamine afforded an amidoximes 9a,b that could be cyclized into 1,2,3-triazole-4-amines 10a,b. In addition, 4a,b could be converted into 4-aminopyrazoles 12a,b via condensation with chloroacetonitrile in the presence of triethylamine as a basic catalyst. Finally, compounds 12a,b were refluxed with dimethylformamide dimethylacetal (DMFDMA) to afford amidines 13a,b that were readily cyclized to the corresponding pyrazolo[4,3-d]pyrimidines 14a,b when refluxed with ammonium acetate.

MICROWAVE-ASSISTED REACTION OF HYDRAZONOYL HALIDES WITH CARBODITHIOIC ACID HYDRAZONES

Hydrazonoyl halides are versatile reagents and their chemistry has received considerable attention.’-3 In basic media, they generate nitrilimines that undergo a variety of 1,3-dipolar Hydrazonoyl halides are also active acylating agents and react with carbanionic species under mild conditions to yield alkylation products that readily cyclize into aromatic heterocycle~.~*~ Despite recent interest in microwave as energy source,1o13 the utility of microwave in reactions of hydrazonoyl halides has received only limited study. In conjunction with our interest in adopting microwave heating in synthesis,1417 we now report the results of ow study of the reactivity of hydrazonoyl halides la-k toward hydrazone carbodithioic acids 2a,b both under microwave irradiation and by conventional thermal heating. To our knowledge this reaction has not yet been investigated. Heating hydrazonoyl halides la-k with 2-cycloalkylidenehydrazine carbodithioic acids (2a,b) in dioxane in the presence of hiethylamine for 1-2 minutes in a microwave oven, or 4-6 hours by conventional thermal heating, afforded products of condensation of the sulfur atom of 2 with two molecules of 1 to lead to 3a-k as shown in Table 1 (Scheme I ) .

Chitosan as heterogeneous catalyst in Michael additions: Reaction of cinnamonitriles with active methyl, active methylenes and phenols

A research on ionic liquids, across many varied applications, is strong and still growing area of interest. New chiral imidazolium-based ionic liquids containing (1R,2S,5R)-(–)-menthol substituent, having symmetrical structure of the salts, have been synthesized and characterized. Monocyclic terpen alcohol: (1R,2S,5R)-(–)-menthol, obtained from a variety of mint (Menthae L.), was used as a substrate in two different reactions to obtain 1,3-bis[(1R,2S,5R)-(–)-menthoxymethyl]imidazolium chloride [1], which is a prototype of chiral ionic liquids. After that, metathesis of this symmetrical imidazolium chloride with various organic and inorganic salts in menthol or water/menthol solution was carried out. The ion exchange reaction goes smoothly, with the satisfactory exceed (from 94 to 99%). Discussed symmetrical salts belong to Chiral Ionic Liquids (CILs) where the chirality resides in the cation and is associated with the presence of optical active (1R,2S,5R)-(–)-menthol. Obtained symmetrical salts are hydrophobic, and airand moisture-stable under ambient conditions. Moreover, they are non-volatile and non-flammable. Some of the 1,3-bis[(1R,2S,5R)-(–)-menthoxymethyl]imidazolium salts [i.e.: chloride, bis(trifluoromethanesulfonyl) imide, acesulfame, saccharinate] possess excellent antielectrostatic properties and their ability to drain the surface charge is similar to these of a known antistatic agent (Catanac 609: American Cyanamin Co.).