Gábor Doleschall

The degradation of carboxylic acids into aldehydes : Regioselective α-acetoxylation of 1,2,4-triazolium salts with diacetoxyiodate(1)anion

Abstract A novel method was developed for degradation of carboxylic acid into aldehydes containing one C atom less whose key step consists in α-acetoxylation of 5-alkyl-3-methylthio-1,4-diphenyl-1,2,4-triazolium iodides by (diacetoxyiodo)benzene. The mechanism of the regioselective α-acetoxylation was studied and the diacetoxyiodate(1)anion was shown to be the actual oxidising agent. Further oxidation reactions of tetraethylammonium diacetoxyiodate(1) were investigated. A novel method was developed for the oxidation of primary alkyl amines into aldehydes by the novel heterocyclic reagent 5-bromo-3-methylthio-1,4-diphenyl-1,2,4-triazolium bromide and diethyl azodicarboxylate.

Novel aldehyde syntheses based on selective reduction of s-triazole derivatives

Abstract Methods are described for synthesising s -triazolium halides ( 5 ) and converting these into aldehydes RCHO, RCH 2 CHO, RCH 2 CH 2 CHO in which R can contain double bonds, halogen, nitr, keto and ester subtituent; have one or two side chains on the α-carbon, or can be alicyclic. A general method for converting α-hydroxyacids to aldehydes is suggested.

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 .

1,2,4-triazines and condensed derivatives—XVI : 1-oxo-1,2-dihydro- and 1-oxo-1,2,6,7-tetrahydro[1,2,4]triazino[1,6-c]-quinazolin-5-ium salts. Synthesis and some reactions☆☆☆

Abstract Methylation of the type 1 and 2 triazinoquinazoliumolates yields the oxotriazinoquinazolinium salts of types 7 and 8 , respectively. 4a similarly furnishes 9 . Acid induced degradations and NaBH 4 reductions of compounds 7–9 , their conversions into the corresponding pseudobases ( 10, 11 ) as well as methods of synthesis of the novel oxotriazinoquinazoliniumolates ( 16 ) are described.

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.

Isoxazole–oxazole conversion by Beckmann rearrangement

A novel base-catalysed isoxazole-oxazole ring transformation was realized in the conversion of ethyl 5-hydroxy-3-(5-methylisoxazol-4-yl) isoxazole-4-carboxylate into 4-cyano-5-methyloxazol-2-ylacetic acid. A new process was developed for the preparation of t-4-amino-c-2-methyl-6-oxotetrahydropyran-r-3-carboxylic acid hydrochloride, a starting material for the synthesis of thienamycin.

1,2,4-triazines and condensed derivatives—XIV : Thermal and acid catalysed degradations of 3-alkylthio-6,7-dihydro-[1.2.4]Triazino[1.6-c]quinazolin-5-ium-1-olates☆

Abstract 3 - Alkylthio - 6,7 - dihydro - [1.2.4]triazino - [1.6-c]quinazolin - 5 - ium - 1 - olates (3), prepared by condensation of 3 - alkylthio -6-(2- aminophenyl) - 1,2,4 - triazin - 5(2H) - ones (1) with aldehydes, ketones or their equivalents are transformed by thermolysis and/or acid treatment into 3 - alkylthio - [1.2.4]triazino[5.6-b]indoles (4) and/or 4-(5- alkylthio - s - triazol -3-yl)- quinolines (5). Alkylation and acylation reactions of the compounds 5 are discussed, as well as their NMR and UV spectra and those of their alkylation and acylation products.

4H-3,1-Benzoxazinone-(4), 2. Mitt.: Die Reaktion von 1,2-Dihydro-2-imino-4H-3,1-Benzoxazinonen-(4) mit nukleophilen Reagentien und ihre Umwandlung in 1,2,3,4-Tetrahydro-chinazolindione-(2,4)

1,2-Dihydro-2-imino-4H-3,1-benzoxazinon-(4) (I a), bzw. das tautomere II a wird durch Wasser, wasr. Alkohole und Amine zu 2-Ureido-benzoesaure (III), bzw. deren Estern und Amiden aufgespalten. Das Hydrochlorid (X) von II a erfahrt dieselben Aufspaltungen unter milderen Reaktionsbedingungen. Unter energischeren Reaktionsbedingungen werden sowohl III als auch seine Ester und Amide zu 1,2,3,4-Tetrahydro-chinazolindion-(2,4) (XII) cyclisiert. Beim Kochen der Amide von III mit Pyridin werden diese in in Stellung 3 substituierte Derivate (XXII) von XII ubergefuhrt. Das 2-Phenylimino-analoge von I a, bzw. II a (I b oder II b) ist gegen Wasser und Alkohole bestandig, mit Benzylamin reagiert es jedoch ebenso wie die Grundverbindung. Das Hydrochlorid von II b reagiert auch mit Wasser und Methanol analog X. Einige der hier und in der vorangehenden Mitteilung besprochenen Umsetzungen sind in Hinblick auf einen Beweis fur den vonKhorana fur durch Carbodiimide hervorgerufene Carboxyl-Kondensationsreaktion vorgeschlagenen Mechanismus von Bedeutung.

4H-3,1-Benzoxazinone-(4), 1. Mitt.: Die Umlagerung von N-(2-Carboxyphenyl)-cyanamiden und N-(2-Carboxyphenyl)-carbodiimiden zu 1,2-Dihydro-2-imino-4H-3,1-benzoxazinonen-(4) und 1,2,3,4-Tetrahydrochinazolindionen-(2,4)

Anthranilsaure und Bromcyan setzen sich in der Kalte zu 1,2-Dihydro-2-imino-4H-3,1-benzoxazinon-(4) (V) um. Unter den gleichen Bedingungen liefert die 1-Methyl- und 1-Benzyl-anthranilsaure sowie das [N-(2-Carboxyphenyl)-glycin]-amid die entsprechenden, am N-1 substituierten 1,2,3,4-Tetrahydro-chinazolindione-(2,4) (XX, XXI, bzw. XV). Mit Phenyl-isothiocyanat liefert das Kalium-anthranilat 2-Thio-3-phenyl-1,2,3,4-tetrahydro-chinazolindion-(2,4) (XXII) und N-(2-Carboxyphenyl)-N′-phenyl-thioharnstoff (XXIII). Letzterer wird durch HgO in das 1,2-Dihydro-2-phenylimino-4H-3,1-benzoxazinon-(4) (XXV) ubergefuhrt.

Synthesis of some new isoxazolylacetic acid derivatives

(3-Chloroisoxazol-5-yl)acetic acid 1, a known acylating agent, useful for the synthesis of semi-synthetic cephalosporins was synthesized by a new route. Several α-substituted 3-chloroisoxazolylacetic acids 9a, b; 10a, b and 15, potential acylating agents for semi-synthetic β-lactams, were also prepared. The (E)and (Z)-3-chloro-α-methoxyiminoisoxazol-5-ylacetic acids 10a, b were separated and their structures unambiguously determined by 1H NMR spectroscopic and X-ray measurements.