Gyula Hornyak

The synthesis of some 3-amino-2-halomethyl-, 2-halomethyl-3-(subst.amino)- and 2-halomethyl-3-hetarylquinazolin-4(3H)-ones as potential plant protecting agents

Abstract A series of N (2)-(2-halomethyl-4-oxo-3,4-dihydroquinazolin-3-yl) carbazates 4 and 5 and 2-halomethyl-3-hetarylquinazolin-4-(3 H )-ones 8 and 9 were obtained by reacting 2-halomethyl-4 H -3,1-benzoaxin-4-ones (12) with alkyl carbazates and hetarylamines, respectively. Some of the carbazates 4 and 5 were obtained alternatively, by treatment of N -(2)-(2-aminobenzoyl)carbazate 15 with haloacetyl halides. The t-butyl carbazates 5 were converted into 3-amino-2-halomethylquinazolin-4(3 H )-ones (6), some of which were further converted into 3-(2,5-dimethylpyrrol-1-yl)-2-halomethylquinazolin-4(3 H )-ones (7). 3-Amino-2-bromomethylquinazolin-4(3 H )-one (6b) was also obtained by brominating its 2-methyl analogue 1 with cyanogen bromide.

Simple and condensed β-lactams. I: The application of diketene in β-lactam synthesis. The synthesis and functional group manipulations of diethyl 3-acetyl-4-oxoazetidine-2,2-dicarboxylates

Abstract Acylation of the N-substituted diethyl aminomalonates 3a – 3d with diketene furnished the ring tautomers 6a – 6d of the expected acetoacetyl derivatives 5 . By treatment with iodine and sodium ethoxide compounds 6a – 6d are smoothly converted into the β-lactam derivatives 2a – 2d . Deethoxycarbonylation of the ethylene ketals 7a – 7d of the latter furnishes mixtures of the corresponding diastereomeric monoesters 8 and 10 . The ethoxycarbonyl groups of the trans esters 8 are more reactive than those of the cis isomers 10 . This permits, under appropriate conditions, selective alkaline hydrolysis and NaBH 4 reduction of the trans esters 8 in the presence of the cis esters 10 . Reduction of the cis ester 10c under more forceful conditions furnishes the trans hydroxymethyl derivative 11c .

Simple and condensed β-lactams. Part 5. The synthesis of some (5RS,6SR)-2-(2-formylaminoethylthio)-6-(2-methyl-1,3-dioxolan-2-yl)carbapenem-3-carboxylic acid derivatives and related compounds

Starting with the 4-oxoazetidine-2-carboxylic acids (3a) and (3b), methods for the synthesis of derivatives of the racemic carbapenem-3-carboxylic acid (2), an analogue of the potent antibiotic thienamycin have heen developed. The synthetic steps included chain elongations by the methods of Arndt-Eistert and Masamune, diazo group transfers, oxidative removals of N-protecting 2,4- dimethoxybenzyl and p-methoxyphenyl groups, cyclization involving a carbene insertion reaction, and conversion of the ketone moiety of the bicyclic compound (13b) into an enethiol moiety via enolphosphate activation. The target compound, the sodium salt (14c) did not possess any useful biological activity.

Benzoxadiazocines, benzothiadiazocines and benzotriazocines—II : The synthesis of 3,4,5,6-tetrahydro- and 1,2,3,4,5,6-hexa-hydro-1,3,6-benzotriazocines

Abstract The general method devised by two of the authors for the synthesis of derivatives of the novel 3,1,6-benzoxadiazocine, 3,1,6-benzothiadiazocine and 1,3,6-benzotriazocine ring systems has been applied to the preparation of a series of 3,4,5,6-tetrahydro- and 1,2,3,4,5,6-hexahydro-1,3,6-benzotriazocines for pharmacological screening.

Simple and condensed β-lactams. Part 7. Side chain extensions of some azetidin-2-one derivatives, and the formation of melillo's lactone, a strategic intermediate in the total synthesis of thienamycin, from 3-acetyl-1-benzyl-4-cyanomethylazetidin-2-one

The oxoazetidinecarboxylic acids (2a) and (2b) and the homologous acid (8b) were converted by treatment of their chlorides with ethyl diazoacetate into the diazo esters (4a, b), and (10b), respectively. Irradiation of the diazo ester (4b) afforded the diethyl and ethyl hydrogen malonates (17) and (18), respectively. Attempted thermal decarboxylation of the latter resulted in profound degradation to give a mixture of the isomeric compounds (19a, b). NaBH4 reduction at –78 °C of the diazo ester (4d) gave mixtures of the diastereoisomers of the diazo esters (4e) and (20). The (hydroxymethyl)-azetidinone (6b) was converted via the aldehyde (5b) and the nitroethyl derivative (22) into the acetals (23) and (25). Attempts to convert the nitrile (7a) into either the acid (8a) or the ester (9a) in acceptable yields, failed. The nitriles (7g) and (7e)[obtained in two steps from the nitrites (7c) and (7b), respectively] were converted by refluxing hydrochloric acid into Melillos lactone (28)(the key intermediate of a practical synthesis of the carbapenem antibiotic thienamycin) and its N-unsubstituted analogue (30), respectively.

Benzoxadiazocines, benzothiadiazocines and benzotriazocines—III : The synthesis of 2-(subst.)amino- and 2-(2-subst.hydrazino)-6-(alkylsulfonyl and arylsulfonyl)-5,6-dihydro-4H-3,1,6-benzothiadiazocines

Abstract A series of derivatives of the novel 5,6-dihydro-4H-3,1,6-benzothiadiazocine ring system has been synthesised for pharmacological screening by application of a method devised earlier by two of the authors. The proof of structure of the benzothiadiazocine derivatives is based on chemical and spectroscopic evidence.

A trifluoromethyl group directed semipinacol rearrangement: synthesis of α-(trifluoroacetyl) diarylmethanes

Abstract Semipinacol rearrangements of trifluoromethyl substituted vic-diol monomethyl ethers proceeded smoothly to give α-(trifluoroacetyl) diarylmethanes in good yields. The trifluoromethyl group gave specific orientation to the course of the rearrangement.

Dissimilar reactivities of diastereomeric 1,1,1-trifluoro-3-(4-methoxyphenyl)-2,3-diphenylpropan-2-ols in an attempted elimination reaction

Abstract Attempted dehydration of a diastereomeric mixture of 1,1,1-trifluoro-3-(4-methoxyphenyl)-2,3-diphenyl-propan-2-ols (6a) with thionyl chloride in the presence of pyridine afforded the rearranged derivative 8 as the main product and only small amounts of the expected olefins (4, 5). Similar treatment of (2RS,3RS)-6a gave the rearrangement product 8 exclusively, while transformation of (2RS,3SR)-6a resulted in the formation of compounds 4, 5 and 8. The different reactivity of the diastereomers is rationalised.

Simple and Condensed β-Lactams. Part 6. A Synthesis of the p-Nitrobenzyl Esters of the Racemic Forms of the Carbapenem Antibiotics PS-5 and PS-6 and Their 6-Epimers.

Die aus den Komponenten (Ic) und (II) erhaltlichen Azetidinone (IIIa) bzw. (IIIb) (jeweils cis/trans-Gemisch) werden zu den Monoestern (IV) (cis/trans- Gemische jeweils getrennt) umgesetzt, aus denen uber die angegebenen Stufen die Verbindungen (VIII) zuganglich sind.