Diazabicycloalkanes with bridging nitrogen atoms. 23. Synthesis and properties of benzo[f]-1,5-diazabicyclo[3.2.2]nonen-3-ol

Intramolecular cyclization 1-(2-hydroxyethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-ol gives benzo[f]-1,5-diazabicyclo[3.2.2]nonen-3-ols. Further treatment with acetic anhydride gives their 3-acetyl derivatives. The stereoisomers have been separated and their substituent configurations shown by PMR spectroscopy.For Communication 22 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 971–975, July, 1991.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 6. Synthesis and some properties of benzo[f]-1,5-diazabicyclo[3.2.2]nonene and benzo[g]-1,6-diazabicyclo[4.2.2]decene

The reaction of N-acetyl derivatives of N,N-trimethylene- and N,N-tetramethylene-o-phenylenediamines with ethylene oxide gave the corresponding N-(-hydroxyethyl)-N-acetyl derivatives, the cyclization of which in refluxing hydrobromic acid leads to benzo[f]-1,5-diazabicyclo[3.2.2]nonene and benzo[g]-1,6-diazabicyclo[4.2.2.]decene.See [1] for Communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1538–1542, November, 1981.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions 20. Synthesis of naphtho[2,3-b]-1,4-diazabicyclo[2.2.2]octene

Reaction of 2-acetamido-3-bis(2-hydroxyethyl)aminonaphthalene with phosphorus oxychloride leads to the formation of 2-methyl-1-(2-chloroethyl)naphtho[2,3-d]imidazole, while reaction with hydrobromic acid gives naphtho[23-b]-1,4-diozabicyclo[2.2.2]octane in 13% yield. The yield of the latter can be increased to 45% by exchange of the hydroxyl groups in the starting material by chlorine and by deacetylation.For Communication 19, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 97–100, January, 1991.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions.

1-Methyl-1-(-haloethyl)-1,2,3,4-tetrahydroquinoxalinium salts were synthesized and the dependence of the hydrolysis and cyclization rate constants on the acidity of the medium and presence of halide was found. It was determined that the monocations of tetrahydroquinoxalines participate in the formation of the benzo[b]-1,4-diazabicyclo[2.2.2]octene system, since blocking the free electron pair of the tertiary nitrogen atom with a methyl substituent significantly accelerates the cyclization and suppresses the hydrolytic side reaction.For Communication 17, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 372–378, March, 1989.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 3. The benzo[b]-1,4-diazabicyclo [2.2.2]-octene system

Benzo[b]-1,4-diazabicyclo[2.2.2]octene and 4′-methylbenzo[1′,2′-b]-1,4-diazabicyclo[2.2.2]octene were synthesized by the reaction of N-acetyl-6-H- and 6-methyl-1,2,3,4-tetrahydroquinoxalines with ethylene oxide and subsequent cyclization of the N-(β-hydroxyethyl)-N'-acetyl derivatives in refluxing HBr. The errors of the published data on the benzo[b]-1,4-diazabicyclo[2.2.2]octene system are demonstrated. See [1] for communication 2. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 827–830.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions. 15. Reactions of benzo[b]-1,4-diazabicyclo[2.2.2]octene monoquaternary salt derivatives with nucleophilic reagents

Monoquaternary salt derivatives of benzo[b]-1,4-diazabicyclo[2.2.2]octene react with piperidine and sodium methoxide or 4-tert-butylthiophenoxide to give primarily N,N-disubstituted tetrahydroquinoxalines. Rate constants have been measured for these bimolecular reactions. Based on their levels of reactivity, these quaternary salts behave as typical alkylating agents.For communication 14, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 966–972, July, 1987.     

Diazabicycloalkanes with nitrogen atoms in nodal positions. 13. Reactions of benzo[b]-1,4-diazabicyclo[2.2.2]octene with electrophiles

The reactions of electrophiles with benzo[b]-1,4-diazabicyclo[2.2.2]octene have been examined. Electrophilic substitution is found to take place in the aromatic ring under severe conditions, in the case of halogenation giving high yields. The structures of the electrophilic substitution products indicate that the heteroatoms have a m-directing influence.For Communication 12, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1239–1245, September, 1986.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions. 16. Synthesis and properties of benzo[b]-1,4-diazabicyclo[2.2.2]octene and dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene,containing primary aromatic amino acids

4-Aminobenzo[1,2-b]-1,4-diazabicyclo[2.2.2]octene and 4-aminodibenzo[1,2-b, e]-1,4-diazabicyclo[2.2.2]octadiene have been prepared by cyclization reactions of N--chloroethyl derivatives of 1,2,4-triaminobenzene and aminophenazine, and subsequent catalytic hydrogenation of the corresponding 4-nitrobenzo[1,2-b]-1,4-diazabicyclo[2.2.2]octene and 4-benzylaminodibenzo[1,2-b,e]-1,4-diazabicyclo[2.2.2]-octadiene. Using the conversion of these compounds to azides as an example, we have demonstrated the feasibility of applying these primary aromatic amines for the synthesis of derivatives of these heterocycles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 831–837, June, 1988.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 5. Synthesis and some reactions of 2-hydroxymethyl-1,4-diazabicyclo [2.2.2]octane

2-Hydroxymethyl-1,4-diazabicyclo[2.2.2]octane was synthesized by reduction of 1,4-diazabicyclo[2.2.2]octane-2-carboxylic acid or its methyl ester with lithium aluminum hydride in tetrahydrofuran and by hydrolysis or hydrogenation of 2-benzyloxymethyl-1,4-diazabicyclo[2.2.2]octane. Depending on the conditions, 2-hydroxymethyl-1,4-diazabicyclo[2.2.2]octane reacts with methyl iodide to give primarily either a bisquaternary or a monoquaternary derivative. The latter is the only product in its alkylation with methyl esters of benzoic and caproic acids.See [1] for Communication 4.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1404–1407, October, 1980.     

Diazabicycloalkanes with nitrogen atoms in the junction positions. 11. Synthesis of dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene

The reaction of ethylene oxide with phenazine followed by treatment with HCl gives N-(2-hydroxyethyl)phenazinium chloride, which yields N-2-haloethyl derivatives of phenazine in a mixture with products of their one-electron reduction when the hydroxyl group is exchanged for a halogen. Heating of these mixtures in the presence of sodium borohydride results in intramolecular cyclization with the formation of a new heterocyclic system, viz., dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene.For report 10 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1407–1411, October, 1984.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 7. Synthesis and configuration of 2,3-diphenyl-1,4-diazabicyclo[2.2.2]-octane

The reaction of ethylene oxide with the meso and d,l diasteromers of 1,2-diphenyl-ethylenediamine gave N,N'-bis(-hydroxyethyl)-1,2-diphenylethylenediamines, which upon refluxing with SOCl₂ form N,N'-bis (-chloroethyl)-1,2-ethylenediamines. The latter upon heating in dimethylformamide (DMF) at 150 ° C undergo cyclization to give, respectivley, cis- and trans-2,3-diphenyl-1,4-diazabicyclo[2.2.2]octane. Evidence for the spatial orientation of the phenyl substituents in the diazabicyclooctanes obtained was obtained by means of an analysis of the multiplicity of the methylene protons in the PMR spectra. The vicinal spin-spin coupling constants for the benzyl protons of the isomeric 2,3-diphenyl-1,4-diazabicyclo[2.2.2]octanes in the ¹³C-H satellites were measured. The values obtained were compared with the literature data and with the dihedral angles calculated from mechanical models of the molecules.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 1. pp. 95–100. January, 1982.The authors thank V. I. Mamatyuk and Yu. V. Gatilov for their assistance in interpreting the PMR spectra and performing the mathematical calculations.     

Diazabicycloalkanes with bridgehead nitrogen atoms. 19. Reactions of monoquaternary salts of dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene with nucleophilic reagents

The monoquaternary salt of dibenzo[b,e]-1,4-diazabicyclo[2.2.2]octadiene reacts with piperidine, 1,3-propylenediamine and sodium p-nitrophenolate with the formation of N,N-disubstituted dihydrophenazines. In its degree of reactivity level, the compound studied is comparable with a typical alkylating agent, such as methyl iodide.For Communication 18, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1106–1108, August, 1989.     

Diazabicycloalkanes with nitrogen atoms at the nodal positions. 12. Stephens rearrangement in substituted 1,4-diazabicyclo[2.2.2]octanes

The ylides formed from phenacyl derivatives of substituted diazabicyclooctanes decompose to the initial base or give products of the Stephens rearrangement, leading to an expansion of the ring. The direction of the reaction is determined by the presence of C-substituents in the bicyclic fragment. C-Phenyl groups, which are capable of stabilizing the transition state, ensure the occurrence of the rearrangement reaction.For Communication 11, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 664–668, May, 1985.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 21. Heteroatom-promoted lithiation of benzo[b]-1,4-diazabicyclo[2.2.2]octene and introduction of substituents into the annelated benzene ring

The action of n-butyllithium on benzo[b]-1,4-diazabicyclo[2.2.2]octene leads to lithiation in the 3 position of the aromatic ring. The reaction of this lithium derivative with electrophilic reagents was used to synthesize 3- and 3,6-substituted derivatives of benzo[b]-1,4-diazabicyclo[2.2.2]octene.See [1] for Communication 20.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 798–803, June, 1991.     

Diazabicycloalkanes with nitrogen atoms in the nodal positions. 4. Intramolecular cyclization of N-(β-x-ethyl)-1,2,3,4-tetrahydroquinoxalines and behavior of benzo[b]-1,4-diazabicyclo[2.2.2]octenes in acidic media

The intramolecular cyclization of N-(β-hydroxyethyl)-N'-acetyl-1,2,3,4-tetrahydroquinoxaline in refluxing HBr was investigated by liquid microcolumn chromatography. Under these conditions the amide group undergoes rapid hydrolysis, the hydroxy groups undergo relatively slow exchange by bromine, and the resulting N-(β-bromoethyl)-1,2,3,4-tetrahydroquinoxaline undergoes cyclization to give benzo[b]-1,4-diazabicyclo[2.2.2]octene. These transformations terminate with the establishment of equilibrium between VII and I. 7-Methyl-N-(β-chloroethyl)-1,2,3,4-tetrahydroquinoxaline similarly forms an equilibrium reaction mixture in HBr. The effect of various factors (the acid and bromide ion concentrations, the character of the acid, and the temperature) on the position of the equilibrium of the compounds obtained and on the occurrence of side reactions (hydrolysis and dealky lation) was studied. See [1] for communication 3. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 831–836, June, 1980.     

Diazabicycloalkanes with bridgehead nitrogen atoms. 28. Stevens rearrangement of benzodiazabicycloalkenes

Stevens rearrangement of the benzyl bromides of benzo[b]-1,4-diazabicyclo[2.2.2]octene and benzo[f]-1,5-diazabicyclo[3.2.2]-nonene occurs with expansion of the diazabicyclic fragments to form a mixture of stereoisomers. Both the ethylene and the trimethylene bridges participate in the rearrangement of the nonene.For Communication 27 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 383–387, March, 1993.     

Synthesis of cis-1,5-Dimethyl-2,4-dinitro-2,4-diazabicyclo[3.1.0]hexan-3-one and cis-1,5-dimethyl-2,4-dinitro-2,4-diazabicyclo[3.2.0]heptan-3-one

cis-1,5-Dimethyl-2,4-dinitro-2,4-diazabicyclo[3.2.0]heptan-3-one and cis-1,5-dimethyl-2,4-dinitro-2,4-diazabicyclo[3.1.0]hexan-3-one were both synthesized in three steps each from a common precursor, 1,3-diacetyl-4,5-dimelhyl-4-imidazolin-2-one.     

Diazabicycloalkanes with nitrogen atoms in nodal positions. 14. Synthesis of dibenzo[1′,2′-b,e]-1,4-diazabicyclo[2.2.2]octadienes containing a tertiary amino group in the aromatic ring

The corresponding 2-amino derivatives of phenazinium salts were obtained by the action of dimethylamine and morpholine on N-(2-hydroxyethyl)phenazinium chloride. The subsequent exchange of the hydroxyl group for chlorine and the reductive cyclization of 2-amino derivatives of N-(2-chloroethyl)phenazinium salts leads to 4-aminodibenzo[1,2-b,e]-1,4-diazabicyclo[2.2.2]octadienes, together with unsubstituted dibenzo-[b,e]-1,4-diazabicyclo[2.2.2]octadiene and the corresponding 2-aminophenazines.For Communication 13, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1658–1661, December, 1986.