Ferenc Csende

Preparation and steric structure of tricyclic and tetracyclic saturated or partially saturated 1,3-heterocycles containing a saturated isoindolone moiety

From cis-2-(p-methylbenzoyl)-1-cyclohexanecarboxylic acid (1) and dien- do-3-(p-methylbenzoyl)bicyclo[2.2.1]heptane-2-carboxylic acid (2) with α,ω-alkylenediamines, the perhydroimidazo[2,1-a]isoindolone (3), the corresponding perhydropyrimido and perhydrodiazepino derivatives (4) and (5) and their methylene-bridged tetracyclic analogues (6-8) were obtained. Compound (1) and ethanolamine yielded the perhydro-1,3-oxazo- lo [2,3-a]isoindolone derivative (9), while (1) with 3-amino-1-propanol or 2-aminoethanethiol gave the homologous saturated 1,3-oxazino deriva- tive (10) and thiazoloisoindolone derivative (11), respectively. On boiling in xylene, (9) was transformed to the hydroxyethylisoindolone (12). From (1) and o-phenylenediamine, the trans-isoindolo[2,1-a]benzi- midazole derivative (13) was formed, while (1) and o-aminothiophenol gave the partly saturated cis-benzthiazole analogue (14)

4- and 5-oxocarboxylic acids as versatile synthons for the preparation of heterocycles

Conversions of 4- and 5-oxocarboxylic acids for the preparation of heterocycles are discussed. The review illustrates the importance and variability and presents the synthetic applicability of these versatile synthons.

Acid- and Base-Promoted Rearrangements of Cycloalkane-Fused Heterocycles

Abstract: Certain cycloalkane-anellated heterocycles undergo rearrangement under basic or acidic conditions via ring-contraction, ring-expansion or ring-opening pathways to afford new or unusual compounds. The reactivities and properties of cycloalkane-fused heterocy-cles differ significantly from those of heteroaromatic ring systems. Possible mechanisms are also discussed. INTRODUCTION The preparation, chemical behaviour and structural studies of various cycloalkane-condensed heterocycles were earlier reported, and surveyed [1-4]. Certain unsusual and unexpected reactions and products were observed, which prompted us to review such the rearrangements and transformations in connection with the synthe-sis of cycloalkane-fused saturated or partially saturated heterocy-cles. These transformations involve ring-contraction, ring-expansion or ring-opening reactions, which take place under acidic or basic conditions at different temperatures. Isomerization at the chiral carbon atoms has been observed only rarely.

Methods for preparation of γ- and δ-oxo acids as useful synthons for heterocycles

Numerous synthetic routes have been recommended for the preparation of y- and δ-oxo acids. The present paper collects methods which need simple starting materials, procedures and conditions. Many examples are presented, comparing the preparations of aliphatic, cycloalkane, aromatic and hetero ring-containing oxo acids from the aspects of yield, regio- and diastereoselectivity.

Application of t-2-benzoyl-t-5-phenylcyclohexane-r-1-carboxylic acid for the preparation of saturated isoindole-fused heterocycles

t-2-Benzoyl-t-5-phenylcyclohexane-r-1-carboxylic acid 1 reacts with cis-2-aminocyclohexanemethanol to give the saturated cis-isoindolo[2,1-a][3,1]benzoxazine 2. Reaction of 1 with trans-2-aminocyclohex-4-enemethanol yields three diastereomeric isoindolo derivatives 3a–c. Cyclization of 1 with 1,3-diaminopropane results in a diastereomeric mixture of cis-pyrimido[1,2-a]isoindolones 4a,b. With di-endo-norbornane aminoalcohol, 1 reacts to yield a mixture of cis- and trans-annelated diastereomers 5 and 6. In its reactions with di-exo-norbornane and norbornene aminoalcohols, 1 isomerizes to give cis-condensed isoindolo derivatives 7–10. After isolation, the structures were established by 1H and 13C NMR spectroscopy, with up-to-date measuring techniques such as NOEDIF, DEPT, HMQC, 2D-NOESY, 2D-COSY and HMBC and, for 10, X-ray measurements. The results show that, with two exceptions, the trans acid 1 undergoes isomerization to give cis-condensed products.

SYNTHESIS AND STRUCTURAL STUDY OF NOVEL 1,2-DIAZEPINONES AND AZABICYCLOOCTANE DERIVATIVES

Condensation of 3-toluoyl-l,2,2-trimethylcyclopentane-l-carboxylic acid 2 with hydrazine, diamines or 3-aminopropanol afforded the novel bicyclic 1,2-diazepinone 3 or various condensed azabicyclooctane derivatives 4-6, respectively. Further transformations of the 1,2-diazepinone 3 to its perhydro 7 and TV-methyl 8 derivatives are also described. Compound 3 when treated with Zn/HCl resulted in the azabicyclo[3.2.1] octanone derivative 9 by a stereoselective ring contraction. Lactone formation from 3 on treatment with acetic anhydride has also been attempted. Introduction δ-Oxocarboxylic acids are useful and versatile synthons for synthesis of several alkaloids and heterocycles possessing a range of pharmacological properties (1-11). These results prompted us to investigate the reaction of 3-aroyl-l,2,2-trimethylcyclopentane-l-carboxylic acids with bidentate nucleophiles since such cyclocondensation reactions of δ-oxocarboxylic acids having a cyclopentane skeleton have not been reported. The starting oxocarboxylic acids can be prepared easily from camphoric anhydride by Friedel-Crafts reaction which was studied recently in detail including a qualitative structure-reactivity relationship on substituted benzene derivatives (12-15). Results and Discussion In this paper we wish to report on the cyclocondensation reactions of 3-p-toluoyl-1,2,2-trimethylcyclopentane-l-carboxylic acid 2 with hydrazine, 1,2-ethylendiamine, 1,3-propylendiamine and 3-aminopropanol leading to representatives of new ring systems. Some further transformations of the products and our efforts to prepare a new lactone by intramolecular cyclisation of 2 are also reported. We tried in vain to cyclize 2 with hydrazine under reflux in toluene for several hours according to the widely used method for the cyclocondensation of δ-ketoacids with hydrazine. Therefore we modified the reaction conditions and refluxing (-180 °C) 1,2-dichlorobenzene was found to be the best solvent. Thus we obtained the bicyclic 5,6-dihydro-4//-l,2-diazepin-7(l//)-one derivative 3, a novel type of the diazepinones after 3 hours reflux in moderate (37 %) yield (Scheme 1).