Application of a thermal rearrangement reaction to questions of structure of condensed dihydrodiazepinones: The reaction of 2,3-diaminopyridine with ethyl benzoylacetate

The condensation of an unsymmetrical aromatic diamine with a β-ketoester can afford two theoretically possible dihydrodiazepinone products, differentiation between which is, at best, difficult and laborious. A recently described (3) rearrangement reaction, whereby dihydrodiazepinones are thermally converted into N-substituted imidazolones, has now been applied to the elucidation of structures of ambiguous diazepinone derivatives. By means of the thermal rearrangement method, the diazepinone derivative resulting from the reaction of 2,3-diamino-pyridine and ethyl benzoylacetate, for which structures 1a and 1b are equally plausible, has been definitively characterized as the 2-phenyl-4-one compound, 1a .     

Reaction of 4,5-diaminopyrimidine and ethyl acetoacetate: Synthesis and chemistry of isomeric dihydropyrimido[4,5-b][1,4] diazepinones

Depending upon reaction conditions, 4,5-diaminopyrimidine and acetoacetic ester gave a variety of condensation products, including the two isomeric dihydropyrimido[4,5-b][1,4]-diazepinones. Under conditions leading to bicyclic products, the formation of 1,5-dihydro-4-methyl-2H-pyrimido[4,5-b][1,4]diazepin-2-one ( 2 ) was strongly favored. The isomeric 3,5-dihydro-2-methyl-4H-4-one compound ( 4 ) was best obtained by cyclization of ethyl 3-(4-amino-5-pyrimidylamino)crotonate ( 3 ) under base catalysis. Thermal rearrangement of 2 and 4 proceeded, in each instance, with loss of the isopropenyl moiety and gave 8-purinone. Compound 4 underwent ring contraction under the influence of alkoxide to yield a product which was shown to be the 7-isopropenyl-8-purinone ( 6 ).     

Synthesis of pyrazolo[3,4-b][1,4]diazepines and pyrazolo[3,4-b]pyrazines

The synthesis and structure elucidation of new pyrazolo[3,4-b][1,4]diazepines and pyrazolo[3,4-b]pyrazines are reported and the characterisation of isomers and tautomers by proton and carbon-13 nmr are discussed. In some case only NOE experiments allow us to identify the isomeric structure.     

Synthesis of pyridazino[3,4-b]quinoxalines and pyrazolo[3,4-b]-quinoxaline by 1,3-dipolar cycloaddition reaction

The pyridazino[3,4-b]quinoxalines 6a,b and pyrazolo[3,4-b]quinoxaline hydrochloride 9 were synthesized by the 1,3-dipolar cycloaddition reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5 with dimethyl or diethyl acetylenedicarboxylate and 2-chloroacrylonitrile, respectively. The reaction mechanisms were postulated for the formation of 6a,b and 9 .     

Thienoquinolizidinones. Synthesis and rearrangement into new piperidino[1,2-a][1,3] or [1,4]diazepinones fused to a thiophene ring

A convenient route to thienoquinolizidinones is described starting from ethyl pipecolinate and suitable halogenomethylthiophenes or 3-chloromethylbenzothiophene. The Schmidt reaction and the Beckmann rearrangement of oximes of these ketones led to piperidino[1,2-a][1,3] or [1,4]diarepines fused to a thiophene ring.     

Synthesis of [1]benzopyrano[3,4-b] [1,4]oxazines as potential antidepressants

Stereospecific syntheses, from Δ-3-chromene, of cis and trans-4-aminochroman-3-ols, 5 and 8 , and their conversion into cis and trans-1,2,3,4a,5,10b-hexahydro[1]benzopyrano[3,4-b][1,4]-oxazines, 15 and 16 , are described.     

Synthesis of enantiomerically pure perhydrofuro[3,4-b]pyrans and perhydrofuro[3,4-b]furans

Olefinic diols, prepared from (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde via olefination and hydrolysis, were converted into enantiomerically pure hydroxy substituted tetrahydrofuran derivatives by cyclization using N-phenylselenophthalimide and BF₃. The PhSe group in the C-4 position of these tetrahydrofurans was then substituted by an allyl group using allyltributylstannane in the presence of AIBN. The selenium promoted cyclizations of the allyl tetrahydrofurans in which the OH and the allyl groups are trans to each other formed the enantiopure perhydrofuro[3,4-b]pyrans, while the cyclization of the allyl tetrahydrofurans in which the OH and the allyl groups are cis gave rise to the perhydrofuro[3,4-b]furans. These bicyclic products were finally deselenenylated with triphenyltin hydride and AIBN.     

Synthesis of condensed tricyclic pyrazolo[3,4-b]thieno[2,3-d]pyridine and related isostere derivatives

In this paper we report the synthesis of an isosteric series of new heterotricyclic derivatives, corresponding to pyrazolo[3,4-b]thieno[2,3-d]pyridine ( 1 ), pyrazolo[3,4-b]furano[2,3-d]pyridine ( 2 ) and pyrazolo[3,4-b]pyrrolo[2,3-d]pyridine ( 3 ). These functionalized compounds were obtained, in high overall yield, by an ‘one-pot’ reaction of the chloroester intermediate 4 , possessing the pyrazolo[3,4-b]pyridine system, with an adequate α-hetero-acetyl ester derivative, in SNAr/Dieckman cyclization type consecutive reactions.     

Pyrazolo[3,4-e] [1,4] thiazepines: Synthesis and structure proof

Pyrazolo[3,4-e][1,4]thiazepine derivatives were obtained by reacting 5-amino-1,3-dimethylpyrazole with arylaldehydes or ketones and mercaptoacetic acid. The structure proof of these derivatives was carried out by identifying the benzylpyrazole products obtained by desulfurization and subsequent hydrolysis, and by comparison of the spectral data of a series of analogous pyrazolothiazepines. Treating the pyrazolothiazepines with sodium hydride and methyl iodide in dimethylformamide or dimethylsulfoxide resulted in a ring contraction with the elimination of sulfur, to yield the pyrazolopyridones in addition to the N-methylpyrazolothiazepines.     

Synthesis of substituted 1-benzyl-2,4,6-triphenyl-2,3-dihydro-pyrazolo [3,4-b] [1,4]diazepines

The acid catalyzed condensation of 4,5-diaminopyrazoles and chalcones gave the hitherto unknown 1-benzyl-2,4,6-triphenyl-2,3-dihydropyrazolo[3,4-b][1,4]diazepines derivatives. The structure of all products was supported by ir, ¹H and ¹³C-nmr and mass spectra.     

Synthesis of substituted 5H-pyradazino [3,4-b]-1,4-benzoxazine (3,4-diazaphenoxazine)

10-Methyl-2-chloro- and 2-chloro-3-methyl-3,4-diazaphenoxazines as well as 2-oxo-3,10-dimethyl-2,3-dihydro-3, 4-diazaphenoxazine were obtained by methylation of 2-chloro-3,4-diazaphenoxazines. Depending on the conditions, alkylation of 2-chloro-3,4-diazaphenoxazine with -diethylaminoethyl chloride gave 1-ethylimidazolino[1,21,2]pyridazo[3,4-b]-1,4-benzoxazine or 2-ethoxy-10-(-diethylaminoethyl)-3,4-diazaphenoxazine. A number of 10-alkyl- and 10-dialkylaminoalkyl-2-chloro-3,4-diazaphenoxazines were obtained by condensation of 3,4,6-trichloropyridazine with substituted o-aminophenols.See [1] for communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 750–754, June, 1971.     

Synthesis of hexahydroazonino[5,6-b]indoles from hexahydroazepino[4,3-b]-and-[3,4-b]indoles and activated alkynes

A reaction of substituted hexahydroazepino[4,3-b]-and-[3,4-b]indoles with activated alkynes was studied. A one-step method for the synthesis of isomeric hexahydroazonino[5,6-b]indoles different by positions of the double bond in the azonine ring was developed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2244–2250, November, 2007.     

Reactions of furoxano[3,4-b]quinoxaline with alkynes and alkenes. Synthesis of pyrazino[2,3-b]quinoxaline 1,4-dioxides

Pyrazino[2,3-b]quinoxaline 1,4-dioxides 3a-e were prepared by reacting Furoxano[3,4-b]quinoxaline with alkynes and alkenes.     

Synthesis of 1H-thieno[3,4-c]pyrazoles,thieno[3,4-b]furans,selenolo[3,4-b]furans and pyrrolo[3,4-d]thiazoles

Starting from the readily available aryl 2-methyl-5-phenyl-3-furyl ketones, 5-methyl-1H-1-phenylpyrazole-4-yl ketones and 4-methyl-2-phenyl-5-thiazolylcarboxaldehyde, a series of 2-phenyl-4-arylthieno[3,4-b]-furan, 2-phenyl-4-(p-methoxyphenyl)selenolo[3,4-b]furan, 4-aryl-1H-1-phenylthieno[3,4-c]pyrazole and 5-benzyl-2-phenylpyrrolo[3,4-d]thiazole were prepared in high yield.     

Synthesis and structural characterization of substituted thieno[2,3-b]pyridines from o-chloroformyl-1,4-dihydropyridines

Novel 4,7-dihydrothieno[2,3-b]pyridines 10a-d have been prepared in a one step procedure from the readily available o-chloroformyl substituted 1,4-dihydropyridines 9a-d and ethyl mercaptoacetate in good yields. Semiempirical calculations reveal a favoured geometry with a boat conformation in the dihydropyridine system and a planar thieno ring. The calculated charge density values for the olefmic carbons (C5 and C6) are in agreement with the experimental push-pull effect observed in the ¹³C nmr.     

Selenium heterocycles. XXXIII. Synthesis of thieno[3,4-b]furan,seleno[3,4-b]furan,thieno[3,4-b]indole and seleno[3,4-b]indole. four novel heterocycles

Starting from the readily available 2-methyl-3-benzoylfuran, 1-phenylthieno[3,4-b]furan and 1-phenyl-seleno[3,4-b]furan were prepared. Also, starting from phenyl 3-methylindol-2-yl ketone and aryl 2-methyl-indole-3-yl ketones a series of substituted thieno[3,4-b]indoles and substituted seleno[3,4-b]indoles were prepared.     

Synthesis and keto-enol tautomerism of ethyl 4-oxo-3,4-dihydro-1H-pyrano[3,4-b]quinoline-3-carboxylate

An efficient method has been developed for the synthesis of a novel β-keto ester-containing pyranoquinoline compound, i.e., ethyl 4-oxo-3,4-dihydro-1H-pyrano[3,4-b]quinoline-3-carboxylate. The method entails a two-step synthesis. The first step involves the Williamson-type reaction of ethyl 2-bromomethyl-3-quinoline-3-carboxylate with ethyl hydroxyacetate in anhydrous benzene to afford the intermediate ethyl 2-[(2-ethoxy-2-oxoethoxy)methyl]quinoline-3-carboxylate. The second step includes the Dieckmann condensation reaction of the resulting intermediate in the presence of sodium ethoxide in anhydrous toluene to afford the desired pyranoquinoline containing β-keto ester moiety. Keto-enol tautomerism of the compound thus obtained was investigated by spectroscopic methods.     

Synthesis of quinolono[4,3-b] and [3,4-b]carbazoles potential DNA binders

2-and 3-β-[arylvinyl]indoles, obtained by Wittig-Horner reaction of the corresponding N-benzenesulfonylbromomethylindoles with o-nitrobenzaldehydes, gave 2- and 3-arylcarbazoles respectively upon Diels-Alder reaction with DMAD. On reductive cyclisation, these carbazoles gave the title compounds.