József Nyitrai

The annular desmotropy of S-methyl-5,5-diphenyl-2-thiohydantoin

Abstract The separate existence of two individual desmotropic forms ( 2a and b ) of the S-Me derivative of 5,5-diphenylthiohydantoin which had been originally claimed on the basis of IR evidence, has been proved by X-ray molecular structure determination. This is the established case of annular desmotropy in the azole field.

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.

Light Induced Reductive Ring Contractions of Sixmembered Cyclic Iminium Ions

Photochemically induced reductive ring contractions, previously observed for 2,5-dihydro-1,2,4-triazines, have also been verified for 1,4-dihydropyrimidines 2a,b, the dihydro-1,2,4,5-tetrazine 9, and dihydro-1,3,5-triazines 11a,b giving rise to fivemembered fully unsaturated heterocycles (pyrroles 4a,b, imidazoles 13a,b, and triazole 10, respectively). The 1,4-dihydropyrazines 15a—j tend to decompose in acidified 2-propanol in the dark, but on irradiation they also undergo reductive ring contraction furnishing solely the 1,2,5- triarylpyrroles 16a—d rather than the (a priori also possible) isomeric 1,3,4-triarylpyrroles 17a/mdash;d. In contrast, the 3,6-diphenylpyrid-azine 18 gives the 4-isopropyl-analogue 19 in low yield upon irradiation in hydrogen chloride saturated 2-propanol.

Photochemistry of N-heterocycles. Part 1. Synthesis and photochemistry of some 2(4),5-dihydro-1,2,4-triazines. X-Ray molecular structure of 1-(4-methyl-3,5,6-triphenyl-1,4,5,6-tetrahydro-1,2,4-triazin-6-yl)ethanol

Ethanolic solutions of the hydrochlorides of the mostly new 2(4),5-dihydro-1,2,4-triazines (1)–(4) were irradiated with a high-pressure mercury immersion lamp (λ 300 nm). The salts (1a)–(3a) underwent reductions, ring contractions, and dehydrogenations upon irradiation to yield pyrazoles (5) and (6) along with phenanthroimidazoles (9) and (10). In addition, the 4-methyl-3,5,6-triphenyl-4,5-dihydro-1,2,4-triazinium chloride (3a) furnished the 6-(1-hydroxyethyl) adduct (11) whose structure was assigned on the basis of its 1H and 13C n.m.r. spectra, and an X-ray diffraction study. The 4-(3-hydroxypropyl)dihydrotriazinium chloride (4a) led, in addition to the expected pyrazole (5), to two new products: the aromatic triazine (15) and the oxazinotriazine (21) by photoelimination and intramolecular photosubstitution, respectively.

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.

A novel rearrangement reaction of 2,5,5-triaryl-2-thiazolin-4-ones during thiation

Abstract 2,5,5-Triphenyl-2-thiazolin-4-one ( 7 ) is transformed by P 2 S 5 in boiling dioxane or xylene into N-(3-phenyl-2-benzo[b]thienyl)-thiobenzamide ( 10 ). The chloro substituted derivatives 16 and 17 of 7 react analogously but, in the case of 17 , a by-product which is believed to be the desired 2-thiazoline-4-thione 18 is also formed. The latter may be isomerised subsequently to 20 . The structure of 10 was elucidated mainly by mass spectrometry and X-ray. Various chemical transformations of 10 and its chloro substituted derivatives 19 and 20 are discussed.

Hydantoine, thiohydantoine, glykocyamidine—XXXIII : Durch Lewis-säuren ausgelöste reduktive umlagerungen vom retrobenzilsäure-typ—VIII reaktionen einiger 5,5-diarylthiohydantoin-derivate mit bortrifluorid-ätheraten, bortrifluorid-ätherat/ bortrifluorid-gemischen und galliumbromid

Zusammenfassung 5,5-Diaryldithiohydantoine des Typs 1b werden beim Kochen mit Bortrifluorid-Dimethylatherat oder Bortrifluorid-Dimethylatherat/Bortrifluorid-Gemischen in Toluol oder Chlorbenzol am S(2)-Atom selektiv methyliert oder erleiden daneben unter Abspaltung des Thioxoschwefels eine fruher durch Aluminiumchlorid ausgeloste reduktive Retrobenzilsaure-Umlagerung in Imidazolderivate des Typs 6. Am S(2)-Atom bereits methylierte Derivate werden nur umgelagert, ebenso auch—wenn sie uberhaupt reagieren—Derivate des 5,5-Diphenyl-4-thiohydantoins. Umgekehrt werden 5,5-Diphenyl-2-thiohydantoine (7a–c) durch Bortrifluorid-Dimethylatherat nur S-methyliert, nicht aber umgelagert. Bortrifluorid-Dimethylatherat als selektives Mittel fur die Methylierung vom S(2) von Diaryl-2-thio- und -dithiohydantoinen ermoglicht die glatte Darstellung einiger bisher schwer auganglicher (Di)thiohydantoinderivate (8a, b). Durch Galliumbromid lassen sich 5,5-Diaryl-4-thio- und -dithiohydantoin-Derivate (ahnlich wie mit Aluminiumchlorid) umlagern, wobei in gewissen Fallen das Galliumbromid als milderer Katalysator Vorteile aufweist. In den Fallen, wo die relative Wanderungstendenz von Phenyl- und p-Chlorphenylgruppen in obigen Reaktionen verglichen wurde, zeigten die Phenylgruppen durchwegs die grossere Wanderungstendenz.

Synthesis of pure methyl [(2S,3R,αR)-1-(3-bromo-4-methoxyphenyl)-3-(α-acetoxy)ethyl-4-oxoazetidin-2-carboxylate] and its enantiomer

Abstract Synthesis of key intermediates leading to 2-iso-oxacephems was carried out starting from l - and d -threonine. As predicted in our previous paper (Tetrahedron Lett. 1995, 36, 8303–8306) all diastereomers of 2-iso-oxacephems can be prepared from the appropriate enantiomers of the amino acid threonine. The absolute configuration of the 2,3- and α-carbon atoms in the β-lactam structure was determined by X-ray crystallographic studies.

Photochemistry of N-heterocycles. Part 3. Synthesis and photochemistry of some new dihydro-1,2,4-triazines and their quaternary salts

Several new dihydro-1,2,4-triazines, 1b, 4, 5, 16 and 19, have been synthesized and their structures unambiguously determined. The existence of 1,2- and 1,4-dihydrotriazines, 20 and 22, described in the literature was ruled out. Irradiation of the aromatic triazines 6 and 15 and the novel quaternary dihydro-1,2,4-triazinium salts 4, 5, 19 furnished new evidence for both the reduction pathways and the mechanism of ring -contraction reactions.