Yeldez El Kilany

Dehydrative ring-closure of 3-substituted 2-quinoxalinones to give fused and nonfused pyrazoloquinoxalines

Abstract Reaction of l -ascorbic acid with o -phenylenediamine and arylhydrazines afforded 3-(1-arylhydrazono- l - threo -2,3,4-trihydroxybutyl)-2-quinoxalinones ( 1–6 ). Whereas compounds 1–6 reacted with alkali to give 1-aryl-3-( l - threo -glycerol-1-yl)-flavazoles, the corresponding acetates ( 7 ) underwent deacetylation and rearrangement to 3-[1-aryl-5-(hydroxymethyl)pyrazol-3-yl]-2-quinoxalinones ( 20–24 ). Compounds 20–24 were also prepared from 1–5 by treatment with hot hydroxylamine hydrochloride. The action of boiling acetic anhydride on 1–5 or 7 afforded colorless products identified as the pyrazole acetates ( 15–19 ), which could also be obtained by the acetylation of compounds 20–24 . Deacetylation of 15 gave 20 . Oxidation of 20 with potassium permanganate gave the 5-carboxylic acid 26 . The i.r., n.m.r., and mass spectra of some of these compounds are discussed.

Synthesis of some pyrazole derivatives having l-threo and d-erythro side chains☆

Abstract The mixed bis(arylhydrazones) of l - threo -2,3-hexodiulosono-1,4-lactone rearrange into pyrazolediones. Mono- and bis-(arylhydrazones) of isoascorbic acid were prepared; the latter are present in two forms that afford the same pyrazoledione. Acetylation, benzoylation, and periodate oxidation of these pyrazolediones were studied, and some condensation products from the pyrazole aldehyde were prepared. Some of the i.r. and mass-spectral data were discussed.

Chapter 5 – Recent Advances in the Dimroth Rearrangement: A Valuable Tool for the Synthesis of Heterocycles

Publisher Summary The Dimroth rearrangement (DR) is a translocation of two heteroatoms in a heterocyclic system, with or without changing its ring structure. The conversion of a heterocycle to a rearranged isomeric product can give one or two isomers via anintermediate, which selectively or specifically forms one of them as the major one. The stability of the rearranged product is the driving force for its formation, which may lead to the preference of one isomer. The heteroatoms which exchange positions in the rearrangement are S, N, O, and Se. DR can be divided into two types based on the positions of the translocating heteroatom(s): either both in the ring or one in the ring and the other located in an exocyclic position of that ring. This chapter discusses the translocation of heteroatoms between rings in fused heterocycles, and the translocation of exo-and endo-heteroatoms within a heterocyclic ring. In the process of rearrangement by translocation of heteroatoms between rings in fused heterocycles, the translocated heteroatoms are part of the ring. The translocation process changes the position of the heteroatom or the substituent on that ring leading to either a retained or a changed ring structure. The presence of a heteroatom within a five-membered ring and also at an exocyclic position of the adjacent ring is a promoting factor for the rearrangement. In the translocation of exo-and endocyclic heteroatoms in heterocyclic rings the translocation of heteroatom X (endocyclic in the ring) and Y (exocyclic to the ring) takes place during the rearrangement. All the processes are driven by the stability of the product, solvent, aromaticity of the ring, heteroatom valence, and bulkiness of the substituent.

Facile synthesis and rearrangement of L-threo-2,3-hexodiulosono-1,4-lactone 2-(2-arylhydrazones)

Abstract Controlled reaction of L - threo -2,3-hexodiulosono-1,4-lactone with substituted phenylhydrazines gave the 2-(monoarylhydrazones) ( 2 ), which underwent dehydrative acetylation to 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxohutyro-1,4-lactone 2-(2-arylhydrazones) ( 3 ). The latter reacted with methylhydrazine to give 1-methyl-3-(1-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(2-arylhydrazones) ( 4 ). Reaction of the monoarythydrazones ( 2 ) with phenylhydrazine gave the mixed bishydrazones ( 5 ), which were rearranged by alkali and acidification to the pyrazolediones ( 6 ). Compounds 6 gave triacetyl ( 7 ) and tribenzoyl derivatives ( 8 ), and, on periodite oxidation, the aldehydes ( 9 ), which afforded the monohydrazones ( 10 ). The i.r.. n.m.r.. and mass-spectral data of some of the compounds were investigated.

Reactions of 3-(1-arylhydrazono-L-threo-2,3,4-trihydroxybutyl)-1-methyl-2-Quinoxalinones

Abstract The 1-methyl derivatives ( 3 and 4 ) of 3-(1-phenyl- ( 1 ) and 3-(1- p -bromophenylhydrazono- L - threo -2,3,4-trihydroxybutyl)-2-quinoxalinone ( 2 ) were prepared by methylation. Periodate oxidation of 3 gave 1-methyl-3-[1-(phenylhydrazono)glyoxal-1-yl]-2-quinoxalinone ( 5 ), which, on reduction with sodium borohydride, gave the corresponding 3-[2-hydroxy-1-(phenylhydrazono)ethyl] derivative ( 8 ). Reaction of 5 with hydroxylamine or benzoylhydrazine gave the corresponding 2-oxime ( 6 ) and 2-(benzoylhydrazone) ( 7 ), respectively. Acetic anhydride causes one molecule of 3 or 4 to undergo elimination of two molecules of water, with simultaneous acetylation and ring closure to afford pyrazoles 9 and 10 , respectively. Pyrolysis of the triacetate of 3 led to the elimination of acetic acid from the sugar and the hydrazone residue, to give the 3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl] derivatives ( 9 ). Acetic acid was found to effect the same rearrangement, but without acetylation, of 1 , 2 , and 3 to give the 3-[5-(hydroxymethyl)] derivatives 11 , 12 , and 13 , respectively. The structure of these pyrazoles was confirmed by a series of reactions, including methylation and acetylation. The n.m.r. and i.r. spectra of the compounds were investigated.

On the ring transformation of hydrazine derivatives of l-ascorbic acid into nitrogen heterocyclic derivatives

Abstract l -hreo-2,3-hexodiulosono-1,4-lactone 2-(p-methoxyphenylhydrazone) (1) was condensed with arylhydrazines to give mixed bishydrazones, whose acetylation gave the corresponding di-O-acetyl derivatives. The hydrazone 1 undergoes elimination of one molecule of water per molecule during, the acetylation, and gives 4-(2-acetoxy- ethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(p-methoxyphenylhydrazone), which reacts with methylhydrazine, via a ring transformation process, to give 1-methyl-3-(L-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(p-methoxyphenylhydrazone). Alkali rearranged the mixed bishydrazones to 1-aryl-3-( l -threo-glycerol-1-yl)-4,5- pyrazoledione 4-(p-methoxyphenylhydrazones), which gave triacetyl and tribenzoyl derivatives, and, upon periodate oxidation, afforded 1-aryl-3-formyl-4,5- pyrazolediones 4-(p-methoxyphenylhydrazones) that gave the corresponding phenylhydrazones. The n.m.r. and mass spectra of some of these derivatives have been investigated.

Saccharide (2,4-dichlorophenoxy)acetylhydrazones, the mechanism of heterocyclization under acetylative conditions

Abstract The synthesis of the (2,4-dichlorophenoxy)acetylhydrazones of a number of monosaccharides is described. The reaction of the corresponding d -galactose derivative with acetic anhydride in pyridine was investigated. Penta- O -acetyl- aldehydo - d -galactose (2,4-dichlorophenoxy)acetylhydrazone was prepared by reaction of the hydrazine with penta- O -acetyl- aldehydo - d -galactose, and its 1 H-n.m.r. spectrum indicated its existence as two geometric isomers. Reaction of the pentaacetate with boiling acetic anhydride caused its acetylative heterocyclization into 3-acetyl-5-[(2,4- dichlorophenoxy)methylene]-2-(1,2,3,4,5-penta- O -acetyl- d - galacto -pentitol-1-yl)- 1,3,4-oxadiazoline. A generalized mechanism for the heterocyclization, based on “soft” and “hard” acids and bases, is discussed. d - arabino -Hexos-2-ulose 2-(2,4- dichlorophenoxy)acetylhydrazone 1-phenylhydrazone was also prepared.

Chapter 1 Dimedone: A Versatile Precursor for Annulated Heterocycles

Publisher Summary This chapter explores that dimedone is a versatile precursor for annulated heterocycles. Dimedone(1) is an alicyclic compound having 1,3-dicarbonyl groups flanked by a methylene group and exists in a tautomeric transenolized form where intramolecular hydrogen bonding is not possible. Dimedone is an excellent precursor for partially hydrogenated fused heterocycles where two of the carbon atoms of dimedone are part of the backbone of the formed heterocycles. The chapter illustrates that dimedones structural features and its reactivity to form more functionalized derivatives have led to the construction of a wide range of fused or spiral biheterocycles. Finally, this chapter emphasizes the role of 1 in the synthesis of fused heterocycles, classified according to the size of the ring and the number of heteroatoms in the heterocycle fused to the cyclohexane ring and subdivided according to the heteroatoms and their arrangement in the ring.

Reactions of l-ascorbic and isoascorbic acids with hydrazines related to sulfanilamide drugs

Abstract Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro- l -ascorbic acid or its d -erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-( l -threo-glycerol-1-yl)-1-phenyl- and -1-(p-sulfamylphenyl)-4,5-pyrazole-dione 4-(p-sulfamylphenlhydrazone) and the related 3-( d -erythro-glycerol-1-yl)compounds. Whereas acetylation of l -threo-2,3-hexodiulosono-1,4-lactone 2,3-bis(p-sulfamylphenylhydrazone) (9) and 3-( l -threo-glycerol-1-yl)-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone) (15) gave the O-acetyl derivatives, benzoylation of 15 gave the di-N-benzoy ltri-O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-(p-suIfamylphenylazo) - l -xylo-2-hexulosono-1,4-lactone 2-(p-sulfamylphenylhydrazone). The 3-( l -threo-glycerol-1-yl)-1-(p-sulfamylphenyl)flavazole (35) was prepared by the rearrangement of 3-[(1-p-sulfamylphenyl)hydrazono- l -threo-trihydroxybutyl]-2-quinoxalinont (33). Periodate oxidation of 15,33, and 35 gave 3-formyl-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone), 3-1-[(p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-(p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.

Acyclic analogues of glucosamidine, 1-deoxynojirimycin and N-(1,3-dihydroxyprop-2-yl) derivative of valiolamine as potential glucosidase inhibitors

Abstract The N-(β-hydroxyethyl)acetamidine ( 4 ) was prepared. Mesylation of 8 gave the 1,3-di- O -benzyl-2- O -methanesulfonylglycerol ( 9 ). Nucleophilic displacement of the mesyloxy group in 9 with ethanolamine and morpholine gave 11 and 12 , respectively. Their catalytic hydrogenation gave 2-deoxy-2-(1-hydroxyeth-2-yl)amino-glycerol ( 5 ) and 2-deoxy-2-(morpholin-4-yl)glycerol ( 13 ). The inhibition of the β-D-glucosidase enzyme from sweet almond by 4, 5 and 13–16 has been studied.