Ferenc Miklós

Preparation and Structure of Diexo-Oxanorbornane-fused 1,3-Heterocycles

Via the reaction of diexo-oxanorbomanedicarboxylic anhydride with toluene, the diexo-aroylcarboxylic acid (3a) was prepared, which exists partly as the tautomeric lactol (3b). With bifunctional reagents, 3a yields fused heterocycles containing three-six rings. Thus, alkylenediamines result in imidazole- and 1,3-diazepine-fused oxygen-bridged isoindolones (6a,b), alkanolamines form the oxazole- and 1,3-oxazine-fused oxanorbornene derivatives (7a-c), and o-phenylenediamine undergoes cyclization to furnish the condensed benzimidazole (8). The reaction of 3a with diexo-aminonorbomanecarbohydrazide yields a pyrimidopyridazine containing six condensed rings (9). In a similar reaction with diendo-aminonorbomenecarbohydrazide, cyclopentadiene cleaves off to give the tricyclic retro Diels-Alder product (10). The structures, and particulary the configurations at the oxanorbornane ring systems and the position of the aryl substituent, were established by means of ID- and 2D-NMR spectroscopy and, for 3b and 7c, also by X-Ray measurements.

APPLICATION OF A BALL MILLING TECHNIQUE FOR THE CONDENSATION OF ANTHRANILIC HYDRAZIDES WITH AROMATIC ALDEHYDES TOWARDS 4-QUINAZOLINONE DERIVATIVES

An environmentally friendly method was applied to prepare anthranilic hydrazones and quinazolin-4(1H)-ones from anthranilic hydrazides and a number of aldehydes in solventless medium. The condensations proceeded smoothly under ball milling conditions at room temperature, and the products were obtained in high purity and yield.

Preparation and structure of pyrazolo[3,4-d]pyrimidinones

Abstract By means of the reactions of 5-amino-1-phenyl-4-pyrazolecarbohydrazide 1 with aroylalkane- and (bi)cycloalkanecarboxylic acids, the tri-, tetra- and pentacyclic pyrazolo[3,4-d]pyrimidines 2–6 were prepared. The acetylhydrazide 1a reacted with levulinic acid to yield a pyrazoloazepinone 7, together with the pyrrolopyrazolopyrimidinone 8, by acylation of the primary amine following intramolecular cyclization involving either the pyrazole carbon or the hydrazide imino group. After separation, the structures of the new compounds were established by means of NMR measurements.

Isomerization and application of aroylnorbornene-carboxylic acids for stereoselective preparation of heterocycles

When boiled in acidic or basic solution, diendo-3-aroylbicyclo[2.2.1]heptane-2-carboxylic acids (1 and la) isomerize to exo-3-aroylbicyclo[2.2.1]heptane-endo-2-carboxylic acids (2 and 2a). Similar endo→exo and even exo → endo isomerization of the aroyl group occurred when the Diels-Alder product containing a mixture of 3-exo-p-toluoylbicyclo[2.2.1 ]hept-5-ene-2-endo-carboxylic acid (4) and 3-endo-p-toluoylbicyclo[2.2.1]hept-5-ene-2-exo-carboxylic acid (5) was reacted with bifunctional reagents: o-aminothiophenol, 3-amino-1-propanol, 1,4-diaminobutane or diexo-3-hydroxymethylbicyclo[2.2.1]heptane-2-amine. All the reactions yielded mixtures of norbornene diendo- and diexo-fused heterocycles (6) and (7, 8 and 10, 9 and 11, or 12 and 13), which were separated and whose structures were established by means of IR, 1 H- and 1 3 C-NMR spectroscopy, with DIFFNOE, 2D-COSY, DEPT, HMQC and HMBC measurements.

Preparation of 9-Amino-1,9-diazatricyclo[6.4.0.04,8]dodecane-2,10-dione by a Retro-Diels−Alder Reaction

Treatment of di-endo- or di-exo-3-aminobicyclo[2.2.1]hept-5-ene-2-carbohydrazides (1a and 1b) with ethyl 2-(2-oxocyclopentyl)acetate (2) yields norbornene-condensed 9-amino-1,9-diazatricyclo[6.4.0.04,8]dodecane-2,10-diones 3a and 3b, the condensed bis(lactams) 4a and 4b and (from 1b and 2) the cyclopenta[c]pyridazinone 5. After separation, 3a and 3b both decompose on heating by loss of cyclopentadiene to give 9-amino-1,9-diazatricyclo[6.4.0.04,8]dodecane-2,10-dione (6).

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.

Preparation and structures of isoindolone- or pyrimidone-condensed heterocycles containing a hydroxy group on a cyclohexane or norbornane moiety

With DL-valinol, 3-amino-1-propanol and o-aminothiophenol, aroyl(bi/tri)cyclic lactones 1 and 2 were cy- clized to isoindole- 4-6, 8, 9, pyrimidinone- 10 or thiazepine- 7 condensed heterocycles. The ketal lactone 3 furnished the benzthiazoloisoindole 9 and mixtures of epimeric hydroxyphthalazinoquinazolinones 11 and 12. The structures were es- tablished by means of 1 H and 13 C NMR spectroscopy and in some cases by X-ray crystallography.

Preparation of pyrimido[2,1-a]phthalazines and an aminopyrimido[2,1-a]isoindole by retro Diels–Alder reaction

The reactions of cis-2-p-toluoylcyclohexanecarboxylic acid 1 with endo,endo- or exo,exo-3-aminobicyclo[2.2.1]heptane- and -hept-5-ene-2-carbohydrazides 2, 4 and 3, 5 yielded partly saturated methylene-bridged phthalazino[1,2-b]quinazolinone diastereomers 6a–6b, 7a–7b, 8a–8b and 9a–9b, and phthalazino[1,2-b]quinazolinediones 10–13 containing a trans-condensed cyclohexane ring. After separation of the products, the structures were established by means of NMR methods. The diastereomers 6–9 differ in the configurations of the annelational carbons: the hydrogens attached to them lie either on the same side (a) or in pairs on opposite sides (b) of the ring skeleton. On heating, the mixtures of diastereomeric norbornene derivatives 8 and 9 underwent retrodiene decomposition: cyclopentadiene split off to yield the pyrimido[2,1-a]phthalazine 14 containing a cis-fused cycloalkane ring. The reaction of 4 with the aroylbenzoic acid 15 furnished the benzologue 19 directly, while, after isolation from the reaction mixture of 1 and 5, and on heating, 20 resulted in 21 containing a saturated trans-condensed isoindole moiety by cycloreversion.