Ferenc Bertha

Simple and condensed β-lactams. Part 33. AlCl3 catalyzed ring closures of some 3-aryloxy-4-oxoazetidine-2-carboxylic chlorides to 1H-chromeno[3,2- b]azete-2,8(2aH,8aH)-diones and some reactions of the products

Abstract Carboxylic chlorides 3a–3c , when treated with AlCl 3 , afforded the tricyclic compounds 17a–17c . NaBH 4 reduction of 17a and 17b afforded compounds 11a and 11b . The latter and the related known compounds 4a, 5b, 6a and 7a were used for the preparation of various dihydrochromeno[3,2- b ]azet-2(1 H )-ones and of a 3,4-disubstituted chromane-2-carboxylic ester ( 26 ) of fixed stereochemistry. Catalytic reduction of 8-chloro compound 5b afforded compounds 10b and 25 , the products of simple hydrodechlorination and of azetidinone ring cleavage with concomitant hydrodechlorination, respectively.

On the anomalous behaviour of (3RS,4RS)-[(2RS)-3-acetylthiazolidin-2-yl]-1-(4-methoxyphenyl)azetidin-2-ones towards cerium(IV) ammonium nitrate (CAN). An unprecedented oxidative ring transformation.

Abstract Starting with (2RS,3RS)-1-(4-methoxyphenyl)-4-oxo-3-phthalimidoazetidine-2-carbaldehyde (1) the two diastereoisomeric 4-(3-acetylthiazolidin-2-yl)-1-(4-methoxyphenyl)-3-phthalimidoazetidin-2-ones 4a and 5a were prepared and converted into their 3-allyloxycarbonylamino analogues 4c and 5c, respectively. While the (3RS,4RS,2′SR) isomers 4a and 4c were readily N-deprotected with cerium (IV) ammonium nitrate (CAN) to yield the expected 6a and 6c, respectively, treatment of the (3RS,4RS,2′RS) isomers 5a and 5c with CAN led to compounds 7a and 7c, respectively, via oxidative ring transformation. The structure of compound 7a was established by an X-ray diffraction study. A rationale, based on AM1 and MMX calculations is given for the dissimilar behaviour of the diastereoisomers.

Simple and condensed β-lactams, part 31. Acid catalyzed ring closures and ring transformations of some 3-aryloxy-4-oxoazetidine-2-carbaldehydes

Abstract Carbaldehydes 1a and 1b, when treated with Lewis or Bronsted acids in non-aromatic solvents or in nitrobenzene afford dihydrochromeno[3,2-b]azet-2(1H)-ones of types 4–6 and 10. In toluene, chloro- and fluoro-benzene related compounds of types 7–9 were obtained, in the last named two solvents accompanied by pyrrolidin-2-one derivatives 11–15.

Oxidative cyclization by lead(IV) acetate of 1-(4-methoxyphenyl)-4-(tetrazol-5-ylmethyl)azetidin-2-ones to 3-methoxy-9,9a-dihydroazeto[1,2-a]tetrazolo-[5,1-d][1,5]benzodiazepin-11(10H)-ones and related reactions

Abstract The tetrazolyl groups of azetidin-2-ones 1a-e and 1h interfere with the normal reaction of related azetidin-2-ones with lead(IV) acetate, viz. acetoxylation at C-4, and cause formation of tetracyclic products 3a-e and 3h. Similar reactions take place with ring homologues 1f, 1g and 1i, and with open-chain analogues 11a and 11b.

On the anomalous behaviour of certain 1-(4-methoxyphenyl)azetidin-2-ones towards cerium(IV) ammonium nitrate (CAN). Structure-reactivity studies

Abstract On treatment with CAN, acetylthiazolidinylazetidin-2-one 12 undergoes ring transformation to afford compound 22, similarly to azetidin-2-ones 2a and 2b studied earlier (all with like configurations at C-4 and C-2′). In contrast, acetylthiazolidinylazetidin-2-one 11 is N-demethoxyphenylated under the same conditions, similarly to azetidin-2-ones 1a and 1b studied earlier (all with unlike configurations at C-4 and C-2′). Both epimers, with like as well as unlike configurations at C-4 and C-2′, of acetyloxazolidinyl derivative 7 are N-demethoxyphenylated by CAN. These observations support the mechanism, suggested earlier for the CAN induced novel ring transformation reaction.

Relative migratory aptitudes of hydrogen, benzoyl, 4-methoxyphenyl and 4-nitrophenyl groups in some unsaturated carbenes (vinylidenes)

Abstract ([5-13C] Tetrazol-5-yl)methyl ketones were prepared and subjected to oxidative fragmentation induced by lead tetraacetate. The resulting intermediate [1-13C]-3-oxoprop-1-en-1-ylidenes rearrange, depending on the relative migratory aptitudes of the benzoyl group and the ligands R, either to [3-13C]prop-2-yn-1-ones or to [2-13C]prop-2-yn-1-ones or to mixtures of the two isomers. The 1H and/or 13C NMR spectra of the products allow the three cases to be distinguished. The relative migratory aptitudes were found to be H>PhCO, 4-MeOC6H4>4-O2NC6H4.

Simple and Condensed β-Lactams. Part 28.1 The Synthesis of C-Methylcarumonams and of a Related Bis(carbamate)

Racemic carumonam analogues 2a–d are synthesised and found to be devoid of any bacterial activity; NaBH 4 reduction of 18 affords both epimers of 8c with the (3RS,4RS)-4-[(1RS)] epimer as the main product, and cyclocondensation of phthalimidoacetyl chloride with racemic imine 14 gives rise to the formation of (3RS,4RS)-4-[(1RS)]-15 as a single epimer.

New synthesis of naratriptan

A new synthesis of N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide (naratriptan, la) has been elaborated starting from 1-benzyl-1H-indole-5-carbaldehyde (14b). The 1-benzyl group proved to be an advantageous protecting group in the course of the construction of the ethanesulfonamide and methylpipieridinyl side-chains and it was removed in the last step of the synthesis.

Reductive dehalogenation of 4-halogenomethyl azetidin-2-one derivatives. Synthesis of (4-oxo-azetidin-2-yl)acetonitriles

The stability of the β-lactam ring under reductive conditions was examined in order to find a selective method for the synthesis of (4-oxo-azetidin-2-yl)acetonitrile derivatives. Fifteen variously substituted 4-halogenomethyl-β-lactam derivatives were synthesised and dehalogenated by three reductive methods. It was found that both the substituents connected to the four-membered ring and to the halogenomethyl group, as well as the applied method have considerable influence on the ratio of the resulting ring-containing and ring-opened products. The best conditions have been defined to give – state products – in excellent yields.

Oxidative fragmentations of some azolyl ketones and related compounds induced by cerium (IV) ammonium nitrate (CAN)

In contrast to simple ketones which are stable to CAN, azolyl ketones 3d–3f, 11a, 11b and, in part, 3c and 4c undergo oxidative fragmentation when treated with cerium(IV) ammonium nitrate (CAN).