Quinazolincs and 1,4-benzodiazepines. LXXXVI. The synthesis of imidazothienodiazepines and imidazopyrazolodiazepines

The thieno[3,2-e][1,4]diazepin-2-one ( 1a ), the thieno[2,3-e] [ 1,4] diazepin-2-one ( 1b ), the pyrazolo[3,4-e][1,4]diazepin-2-one ( 1c ) and a chloro analog of 1b , compound 1d , were each converted to derivatives of the novel tricyclic ring systems 4H-imidazo[1,5-a]thieno[2,3-f] [1,4]-diazepine, 4Himidazo[1,5a]thieno[2,3f][1,4]diazepine and 4H-imidazo[ 1,5-a]pyrazolo[4,3-f]-[1,4]diazepine. Depending on the substituents desired on the imidazo ring, two different synthetic pathways were employed.     

Synthesis of 6-substituted 6-nitroperhydro-1,4-diazepines via novel tandem retro-Henry and Mannich/Michael reactions

N,N'-Dibenzyl-6-hydroxymethyl-6-nitroperhydro-1,4-diazepine was converted into a nitronate via retro-Henry reaction, followed by either Michael reaction with several acrylic derivatives or Mannich reaction with different amines, thus leading to 6-substituted 6-nitroperhydro-1,4-diazepines. The tandem retro-Henry/Mannich reaction was also carried out using benzylamine as base, solvent, and reagent at the same time. Selective hydrogenation of the nitro group and complete hydrogenolysis were also successfully achieved.     

Synthesis of 6-amino-1-benzyl-4-methylhexahydro-1H-1,4-diazepine

Five variants (methods A—E) of a synthetic route to 6-amino-1-benzyl-4-methylhexahydro-1H-1,4-diazepine (3b) using N-benzyl-N'-methylethylenediamine (8a) are described. The reaction of 8a with 1-benzenesulfonyl-2-bromomethylaziridine (7) , 2-phenyl-4-(p-toluenesulfonyloxymethyl)oxazoline (13) , and β, β-dibromoisobutyric acid (15) resulted in the direct cyclization to give the precursor of 3b , 6-substituted 1,4-diazepine derivatives 9, 14 , and 16 , respectively (methods A—C). These compounds were transformed into the desired 3b , The preparation of 1,4-diazepine ring from methyl 2-tert-butoxycarbonyl-aminopropenate (18) was alternatively achieved by the intramolecular amidation of the intermediate 19a (method D) or reductive cyclization of the aminoaldehyde 23a (method E). Method E was found to efficiently produce the 6-amino-1,4-diazepine 3b.     

Reactions of 5,6-diamino-1,3-dimethyluracil with carbonyl compounds

The first step in the acid-catalyzed reaction of 5,6-diamino-1,3-dimethyluracil with carbonyl compounds is the formation of an azomethine at the 5-amino group. Chalcone derivatives undergo a further substitution; the 6-amino group is replaced by a hydroxyl group with subsequent ring closure and the formation of a 2,3-dihydro-1,5-oxazepine ring. Azomethines based on arylidenacetones forms 2,3-dihydropyrimidino[5,6-b]-1,5-diazepine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 241–246, February, 1984.     

1,4-Diazepines Bearing Thieno(2,3-b)Thiophene and Cyclohexene Carboxylate Moieties

Bis[thieno(3,2-b)-1,4-diazepine] (4) and bis[imidazo(1′,2′)thieno(3,2-b)-1,4-diazepine (7) derivatives were prepared starting with thieno(2,3-b)thiophenes (1) and (2), respectively. Also, benzodiazepine derivatives (11a–f) were prepared via a reaction of cyclohexenone carboxylates (8a–f) with cyclohexylamine and chloroacetyl chloride followed by cyclization. Also, dibenzoazepines (13) and (14a,b) were prepared via a reaction of (8a) with o-phenylenediamine and o-aminophenol or o-aminothiophenol.     

Reactions of 4,5-diamino-3-methyl-1-phenylpyrazole with diarylideneacetones

The reaction of 4,5-diamino-3-methyl-1-phenylpyrazole with dibenzylideneacetone and its 4,4-derivatives has been studied; the reactions lead to aromatic 1H-2,3-dihydropyrazolo[5,4-b]1,5-diazepine derivatives. The reaction pathway has also been identified.Translated from Khimiya Geterotsiklicheskikh Sodinenii, No. 11, pp. 1563–1567, November, 1987.     

Reaction of (oxindolyl)-aroylcarbinols with 1,2-diamines

(Oxindolyl)aroylcarbinols undergo condensation with 1,2-diamines to give 1,5-diazepine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 797–800, June, 1976.     

Asymmetric synthesis of (R)-6-amino-1-methyl-4-(3-methyl-benzyl)hexahydro-1H-1,4-diazepine from L-asparagine

An efficient asymmetric synthesis of (R)-6-amino-1-methyl-4-(3-rnethylbenzyl)hexahydro-1H-1,4-diazepine [(R)-2] which serves as the amine part of (R)-1, a potent and selective 5-HT₃ receptor antagonist, is described. Formation of the hexahydro-1H-1,4-diazepine ring was achieved by the intramolecular ami-dation of the optically active aminocarboxylic acid 18 or reductive cyclization of the optically active aminoaldehyde 25. Compounds 18 and 25 were prepared from L-asparagine via the key aziridine derivatives 15 and 22 , respectively, with retention of the configuration. The intramolecular aziridine ring opening reaction of 29 gave the C₂? N bond cleavage product of the aziridine ring, the piperazin-5-one 30 , as the main product along with the desired 7-membered ring, the hexahydro-1H-1,4-diazepine product 19 .     

An expedient approach to substituted triazolo[1,5-a][1,4]benzodiazepines via Cu-catalyzed tandem Ullmann C–N coupling/azide-alkyne cycloaddition

An approach to the synthesis of triazolo[1,5-a][1,4]benzodiazepines comprising copper catalyzed tandem Ullmann C–N coupling followed by azide-alkyne cycloaddition has been described. The reaction of o-azidobenzylbromide and N-propargylated aniline derivatives in the presence of CuI and base leads to the formation of triazolo[1,5-a][1,4]benzodiazepines. The reaction has been successfully generalized by synthesizing a number of triazolo[1,5-a][1,4]benzodiazepine derivatives in good to excellent yields.     

Confirmation of the structure of a glucono-1,4-lactone derivative obtained from silylation of glucono-1,5-lactone

Silylation reactions of glucono-1,5-lactone can give the persilylated glucono-1,5-lactone or the persilylated 1,4-lactone depending on the reaction conditions employed. The structure of 2,3,5,6-tetra-O-(tert-butyldimethylsilyl)-d-glucono-1,4-lactone, obtained in 84% yield from the reaction of glucono-1,5-lactone with TBSOTf and lutidine in dichloromethane, has been confirmed by X-ray crystallography. Formation of the glucono-1,5-lactone and manno-1,5-lactone derivatives and other possible products has also been ruled out by synthesis of possible exo-glycal derivatives of these lactones using the Ramberg–Bäcklund rearrangement of the corresponding sulfones.     

Aromatic derivatives of 1H-2,3-dihydropyrazolo[4,5-b]-1,5-diazepine

Aromatic derivatives of 1H-2,3-dihydropyrazole[4,5-b]-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–369, March, 1987.     

Reactions of β-sulfenyl α,β-unsaturated ketones with guanidine,Amidines, and diamines

β-Sulfenyl α, β-unsaturated ketones 1a-c reacted with guanidine or amidines to give pyrimidine derivatives 3 in 14-76% yields. Treatment of ketones 1 with diamines such as ethylenediamine and o -phenylenediamine afforded the seven-membered heterocycles, 2,3-dihydro-1,4-diazepine 5 and 2,3-benzo-1,4-diazepines 8a-c .     

A new class of spermidine-derived alkaloids

[structure: see text] Four new alkaloids, dovyalicins A-D, were isolated from Dovyalis macrocalyx. Their structures were established by two-dimensional COSY, NOESY, HSQC, and HMBC NMR experiments as well as chiroptical methods. The compounds, possessing spermidine as part of a perhydro-1,5-diazocine or a perhydro-1,4-diazepine moiety, constitute a new group of polyamine-derived alkaloids.     

The 6-amino-6-methyl-1,4-diazepine group as an ancillary ligand framework for neutral and cationic scandium and yttrium alkyls

The 6-amino-6-methyl-1,4-diazepine framework is a readily available neutral 6-electron ligand moiety, suitable to support cationic group 3 metal alkyl catalysts; it also provides convenient access to tri- and tetradentate monoanionic ligand derivatives.     

Reactions of functionally substituted benzo[c]pyrylium salts. Synthesis of 5h-benzo-2,3-diazepines

5H-Benzo-2,3-diazepine derivatives are formed in the reaction of 4-ethoxycarbonylbenzo[c]pyrylium perchlorates with excess hydrazine hydrate. It was established that the key intermediate in the reaction is the 2-aminoisoquinolinium cation. A method for the recyclization of 4-cyanobenzo[c]pyrylium salts to 5H-benzo-2,3-diazepine derivatives was found.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1475–1477, November, 1993.     

Reaction of 1,5-Diphenyl-1,4-pentadien-3-one and 1,5-Diphenyl- 1-penten-4-yn-3-one with Monosubstituted Hydrazines

Phenyl- and isopropylhydrazines react with 1,5-diphenyl-1,4-pentadien-3-one to give 4,5,6,7-tetrahydroindazole derivatives instead of the expected 4,5-dihydropyrazoles. The reaction of phenylhydrazine with 1,5-diphenyl-1-penten-4-yn-3-one leads to formation of 1,5-diphenyl-3-phenylethynyl-4,5-dihydropyrazole. 2,4-Dinitrophenylhydrazine reacts with 1,5-diphenyl-1-penten-4-yn-3-one, affording the corresponding unsaturated hydrazone rather than pyrazole derivative.     

Intermediates in the reaction ofo-phenylenediamine with carbonyl compounds and their subsequent conversions

The reaction ofo-phenylenediamine with aldehydes and ketones has been studied using PMR spectroscopy. It has been established that the reaction begins with the formation of monoimines (isolated in condensations with aromatic aldehydes) which are cyclized to the corresponding benzimidazolines. The latter are converted in the reactions involving aldehydes and pinacolone into 2-substituted benzimidazoles, but with acetone and acetophenone give 2,3-dihydro-1H-benzo[b]-1,4-diazepine derivatives.Academy of Military Medicine, Saint Petersburg 194175, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–367, March, 1998.     

Synthèse par cyclisation nucléophile de dérivés de sucres portant un hétérocycle inséré en spiro. Note de Laboratoire

Synthesis of Sugar Derivatives Bearing a Spiro Heterocycle via Nucleophilic Cyclization Treated with the 1,4-binucleophiles 1,2-diaminoethane, 2-aminoethanol, 2-aminoethanethiol, L -cysteine, o-phenylenediamine, o-aminophenol or o-aminothiophenol the ketosugar derivative 1 gave in good yields the corresponding spiro derivatives 2–8 . In each case, the reaction was stereospecific leading to the isomer bearing the N-atom on the endo face of the bicyclic starting material. Starting from the sugar enone 9 , the aromatic 1,4-binucleophiles led stereospecifically to the spirobenzo [b]-diazepine 10 , -oxazepine 11 or -thiazepine 12 . In one case, an imine (13) was isolated. As 13 cyclized to 6 , the intermediate formation of these kind of derivatives could be considered as a common step for all these reactions.     

The synthesis of electron donor-acceptor substituted pyrazoles

A variety of 1,3- and 1,5-donor-acceptor substituted pyrazole derivatives have been synthesized by the cyclocondensation of α,β-ethynyl ketones with substituted phenyl hydrazines. The regioselectivity of the cyclization depends on the reaction conditions in a manner consistent with competitive 1,2- and 1,4-addition followed by ring closure. 1,4-Disubstituted derivatives can be prepared from the corresponding 4-iodopyrazole using palladium catalyzed carbon-carbon bond forming reactions. The pyrazole chromophores are expected to show interesting nonlinear optical properties.     

Regioselective synthesis of 1,2,3-triazole derivatives via 1,3-dipolar cycloaddition reactions in water

Reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields, while similar reaction between a terminal aliphatic alkyne and an azide (except m-nitroazidobenzene) afforded a mixture of regioisomers with the ratio of 1,4- to 1,5-isomers ranging from 3:1 to 28.6:1. Reactions of m-nitroazidobenzene with either arylalkynes or aliphatic alkynes formed only 1,4-disubstituted derivatives in excellent yields.