Géza Stájer

Stereochemical studies 83 saturated heterocycles 76. Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

Abstract The cis - and trans -2-amino-4-cyclohexene-1-carboxylic acids 1 and 3 react with imidates to give the condensed-skeleton, bicyclic cis - and trans -pyrimidin-4-ones 8 and 9 . The amino acids 1 and 3 were reduced to the cis -and trans -1, 3-aminoalcohoIs 6 and 7 , which were cyclized by means of imidates to the bicyclic tetrahydro-4 H -3,1-benzoxazines 10 and 11 , or were converted, via the corresponding carbamates 14 and 15 into the tetrahydro-4 H -3,1-benzoxazin-2(1 H )-ones 16 and 17 . The 2-thioxo analogues 18 and 19 were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols 6 and 7 by treatment with carbon disulphide. The trans -aminoalcohol 7 and its saturated analogue reacted with p -chlorobenzaldehyde to furnish the hexahydro 13 and octahydro-4 H -3,1-benzoxazine 13a , respectively. 1 H and 13 C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized cis isomrs 8 , 10 , 16 and 18 occurred as the preferred conformer in the heterocyclic twist inverse form of N -inside type ( quasiaxial C 6 -N bond) (B). In the trans isomers containing a saturated C-2 atom ( 13 and 13a ), H-2 and H-6 are in cis relative positions.

Stereochemical studies — 79 synthesis and kinetic study on the retrodiene decomposition of norbornene-condensed 1,3-oxazin-4-ones

The cis-cxo- amino acid c with norbornene skeleton was converted into 2-aryvl-cis-cxo-1,3-oxazin-4-ones 5a-d. These compounds, similarly to the diendo isomers 1a-d studied by us earlier, undergo retrodiene decomposition under mild conditions to give 2-aryl-62-l,3-oxazin-6-ones (2a-d) in 50-60% yield. The ratio of the decomposition rate constants of the tricyclic diendo and diexo-1,3-oxazin-4-ones, measured in toluene solution, is about 2.

Saturated heterocycless—35 : Synthesis and conformational analysis of stereoisomeric 2-oxo- and 2-thioxo-cis- and trans-5,6-trimethylene-3,4,5,6-tetrahydro-1,3-oxazines

Abstract cis- and trans 5,6-Trimethylene-3,4,5,6-tetrahydro-1,3-oxazin-2-ones ane 2 thiones (11–20) were synthesized from cis and trans-2-aminomethylcyclopentanols (6–10) by reaction with urea ethyl chloroformate, carbon disulphide or thiophosgene. The cyclization reactions were also successful with the trans-amino-alcohols, at variance with earlier literature data relating to 1,2-disubstituted 1,3-bifunctional trans-cyclopentane derivatives X-Ray diffraction analysis of trans-5,6-trimethylene-3,4,5 6-tetrahydro-1,3 oxazine-2-thione (17) shows that the exocyclic CXXXS sp2 bond takes part in a co-planar delocalized pπ-pπ bond system formed on the S(10) O(1), N(3) and C(2) atoms and consequently both the C(2)-N(3) [1.304(7)a] and C(2)-O(1) [1.337(7)a] bonds gain some multiple bond character. The endocyclic bond angles at C(2) and N(3) are significantly opened, compared with those in related heterocycles. Of the bonds in the six membered hetero ring, C(5)-C(6) is significantly shortened [1.448(9)a] The remarkable ring-closure reaction of the trans cyclopentane derivatives can be explained by the above findings. 1H NMR data on compounds 11–20 suggest conformationally homogeneous systems and the predominance of the O-inside conformers of the cis isomers.

Synthesis and NMR study of norbornane/norbornene-fused tetracyclic azetidinones

Abstract Tetracyclic azetidinones 8 , 9 and 12 – 17 were synthesized. In the cases of 8 and 9 , the main component was isolated from the two-component product of the cycloaddition. The minor component was concentrated to give a mixture, from which a computer technique utilizing the known spectrum of the main component gave the proton resonance spectrum also of the minor component. Only one diastereomer could be isolated for the each of the analogues 12 – 17 . Reaction of the 1,3-oxazine 3 with chloroacetyl chloride gave, besides the azetidinone 12 , the 1,3-oxazine [2,3- b ]-1,3-oxazin-4-one derivative 18 . Configurations and conformations were determined by IR, 1H and 13C NMR spectroscopy.

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)

Preparation and steric structure of condensed-skeleton saturated diphenyl-substituted isoindolones

The Friedel-Crafts reaction of benzene with cis-4-cyclohexene-1,2-dicarboxylic anhydride (1) yields trans-5-phenyl-cis-2-benzoylcyclohexanecarboxylic acid (2), which gave cyclohexane-condensed pyridazinone (3) with hydrazine, and cis-4,5-tetramethylene-1,2-oxazin-8-one (4) with hydroxylamine. From 2 with ethylenediamine, the saturated imidazol[2,3-a]iso-indolone (5) was prepared, while the reaction of 2 with 1,3-diaminopropane furnished a mixture of two isomeric pyrimido[2,3-a]isoindolones (6a,b) in the relative positions of the benzene ring and cyclohexane annelation hydrogens. From the reaction of 2 with 3-aminopropanol, the oxazino[2,3-a]isoindolone (7) was obtained. The reaction of 2 with cis-2-hydroxymethylcyclohexylamine gave the tetracyclic (8), while 2 and diendo-3-hydroxymethylbicyclo[2.2.1]hept-5-enyl-2-amine yielded the isomers (9a,b), which differ in the mutual positions of the phenyl group on the quaternary carbon and cyclohexane annelation hydrogens. 1H and 13C-nmr spectra and DNOE and 2D-HSC measurements proved that the 5-phenyl group is cis-equatorial to the two annelated hydrogens of the cyclohexane ring.

Stereochemical studies. Part 103. Saturated heterocycles part 107. Preparation of 3-mono- and 2,3-di-substituted pyrimidin-4(3H)-ones in retro-diels-alder reactions. the correct 1,2-disubstituted structure of the compounds previously described as 2,3-disubstituted derivatives

The orthoformate cyclization of carboxamides (4) obtained from 3-exo-aminobicyclo[2.2.1]hept-5-ene-2-exo-carboxylic acid (1) yielded intermediate 8,9,10-trinorbornene-fused pyrimidinones (5) and hence 3-substituted pyrimidin-4(3 H)-ones (6) through the splitting off of cyclopentadiene. Analogously, the reaction of carboxamides (4) with orthoacetate or orthopropionate led to the formation of 2,3-disubstituted pyrimidin-4(3H)-ones (8). A comparative i.r. and n.m.r. study of compounds (8) and of the previously described derivatives (9) gave unambiguous evidence for the structure of the new compounds. It was also established unequivocally that the products obtained from propiolate with amidines are not the previously assumed 2,3-disubstituted 4(3H)-ones (8), but are in fact the 1,2-disubstituted pyrimidin-4(1H)-ones (9).

Mass spectrometric and MNDO study of electron impact induced fragmentation of some norbornane- and norbornene-condensed pyrimidinones and oxazinones

Abstract The main electron impact induced fragmentation processes of nine norbornane- or norbornene-condensed 2-aryl-1,3-pyrimidin-4(3H)-ones and six oxazinone analogues were established by means of mass spectrometry and MNDO calculations. The fragmentations involve the common and main process of selective and simple bond cleavage in the norbornane skeleton, followed by McLafferty H-rearrangement, and a competing and hidden retro Diels-Alder (RDA) reaction of the hetero ring. The norbornenes additionally undergo an RDA reaction directed by the CC double bond. The decomposition schemes deduced from mass spectrometric measurements were supported by the theoretical results. MNDO bond orders and charge densities calculated for neutral and ionized model molecules proved to be informative for the interpretation of the observed fragmentations. MNDO heats of formation for neutral and ionized products also indicate the high probability of the suggested main fragmentation processes.

Phenyl-substituted cyclopentane- and cyclohexane-cis-fused-1,3-oxazines and -1,4-oxazepinones. Preparation and stereochemical study

Abstract The cycloadditions of cyclopentene and cyclohexene with benzonitrile oxide (BHO) yielded isoxazolines 1 and 2, which were reduced to 1,3-aminoalcohols 1 and 2 with LAH and cyclized to cycloalkane- cis -condensed 4-phenyl-1, 3-oxazines 3 and 4 5 , 6 . From the aminoalcohol 7 obtained by Na/EfcOH reduction of 2, the diastereomeric 4-phenyloxazine derivative 8 was obtained. 3 and 4 were transformed through carbamates to cis-5,6-trimethylene- and cis-5i6-tetramethylene-1, 3-oxazin-2-ones 3 and 10, while the analogous 2-thiones 7 8 and 9 10 were prepared via dithiocarbamates. With phenyl isothiocyanate, furnished the 2-phenylimino-1,3-oxazine 11 12 , while 1,4-oxazepinones ( 13 14 15 16 ) were obtained with ethyl chloroacetate an3 2-chloropropionate. The structures of the new compounds, Including the configurations and preferred conformations, were elucidated by means of ir, 1H and 13C-nmr investigations.

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.