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 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 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. 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. 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.     

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.     

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 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.     

Synthesis of 1,4-diazabicyclo[2.2.2]octane

Double intramolecular cyclization of N,N-bis(2-chloroethyl)-N-N-bis(2-cyanoethyl)ethylenediamine leads to 1,4-bis(2-cyanoethyl)-1,4-diazoniabicyclo[2.2.2]octane dichloride, which undergoes decyanoethylation to 1,4-diazabicyclo[2.2.2]octane when it is heated. The structures of the compounds were confirmed by their IR and PMR spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 548–550, April, 1978.     

Diazabicycloalkanes with nitrogen atoms in bridgehead positions. 25. Influence of 3′-substituents on the direction of hydroxyethylation of benzo[b]-1,4-diazabicyclo[2.2.2]octenes

Substituents in the 3 and 6-positions of benzo[b]-1,4-diazabicyclo[2.2.2]octane are capable of influencing the reactivity of the nitrogen atoms in the hydroxyethylation reaction due to steric hindrances or anchimeric contribution. Depending on the reaction conditions and substituents in the aromatic ring of benzo[b]-1,4-diazabicyclo[2.2]octane, either mono- or bis-quaternary salts were obtained.For Communication 24, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 215–218, February, 1992.     

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.     

1,4-diazabicyclo[2.2.2]octanes. I. Method for the synthesis of 1,4-diazabicyclo[2.2.2]octanes with functional substituents or condensed with benzene rings

The reaction of substituted 1,4-dimethylpiperazines and tetrahydroquinoxaline with dibromoethane gives the corresponding 1,4-diazabicyclo[2.2.2]octanes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 272–275, February, 1976.     

Pyrimidine derivatives XII. A convenient preparation of 6-formylpyrimidinedione and 2- and 3-formylpyridine derivatives from corresponding nitrooxymethyl derivatives

The convenient preparation of 6-fomylpyrimidinedione derivatives and 2- and 3-formylpyridine are described. Thus, 5-bromo-1,3-dimethyl- ( 1a ), 5-bromo-3-methyl-1-(2-nitrooxyethyl)- ( 1b ), and 5-bromo-3-methyl-1-(3-nitrooxypropyl)-2,4(1H,3H)-pyrimidine-dione ( 1c ) were converted to the corresponding 6-formyl compounds 2a, 2b , and 2c , respectively, in excellent yields by the reaction with triethylamine and 1,4-diazabicyclo[2.2.2]octane. These 6-formylpyrimidinedione derivatives are key intermediates for the preparation of 6-carbon-carbon substituted compounds, which are expected to be potential antitumor and antiviral agents. Similarly, 2-(and 3-)formylpyridine ( 9a (and 9b )) were obtained by the reaction of 2-(and 3)nitrooxymethylpyridine ( 8a (and 8b )) with 1,4-diazabicyclo[2.2.2]octane.     

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.     

Ring-opening reactions of 1,4-diazabicyclo[2.2.2]octane (DABCO) derived quaternary ammonium salts with phenols and related nucleophiles

1,4-Diazabicyclo[2.2.2]octane (DABCO) has been evaluated as a starting material for the synthesis of 1-alkyl-4-(2-phenoxyethyl)piperazines and related derivatives. We found that 1-alkyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, resulting from the alkylation of DABCO, efficiently react with a variety of nucleophiles in polyethyleneglycol (PEG) or diglyme at high temperatures to give piperazine products resulting from the nucleophilic ring-opening reaction. The benzylation side reaction was found to be relevant with softer nucleophiles when using 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, while other types of alkylations were not observed. One-pot methodologies allow for the synthesis of piperazines directly from primary alcohols, alkyl halides or sulfonates, using phenols, or other nucleophile sources, and DABCO.     

Synthesis and selected properties of N-substituted pyrrolo[2,1-c]-1,3-diazacycloalkano[1,2-a]pyrazinones

The reactions of methyl α-(2-formyl-1H-pyrrol-1-yl)carboxylates with N-substituted aliphatic 1,2-, 1,3-, and 1,4-diamines afford new pyrrole-containing heterocyclic systems: 1,2,3,10b-tetrahydroimidazo[1,2-a]pyrrolo[2,1-c]pyrazin-5(6H)-ones, 1,3,4,11b-tetrahydro-2H-pyrrolo[2′,1′:3,4]pyrazino[1,2-a]pyrimidin-6(7H)-ones, and 1,2,3,4,5,12b-hexahydro-pyrrolo[2′,1′:3,4]pyrazino[1,2-a][1,3]diazepin-7(8H)-ones. The reduction of these compounds with different reagents was studied.     

Bis[(tetraphenylporphyrinato)zinc]-calix[4]pyrrole. Synthesis and receptor properties

A new bis[(tetraphenylporphyrinato)zinc]-calix[4]pyrrole conjugate has been synthesized from monoacetyl-substituted tetraphenylporphyrin, and its complexing ability toward 1,4-diazabicyclo[2.2.2]octane has been evaluated by spectrophotometric titration and 1H NMR spectroscopy.     

2-Amino-3-(benzimidazol-2-yl)benzo[b]furans

The corresponding 2-amino-3-(benzimidazol-2-yl)benzo[b]furans were obtained by reaction of 2,3,5-trimethyl-1,4-benzoquinone with 2-cyanomethylbenzimidazoles. It is shown that new benzo[b]furo[2′,3′∶4,5]pyrimido[1,6-a]benzimidazole polynuclear heterocyclic systems (bases and quaternary salts) are formed in the reaction of these products with acylating agents. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 164–166, February, 1980.     

Two novel phase transition materials based on 1-isopropyl-1,4-diazabicyclo[2.2.2]octan-1-ium

Two novel phase transition materials,[C₉H₂₀N₂] [Na(BF₄)₃] (1) and[C₉H₂₀N₂] [(PF₆)₂] (2), were synthesized based on 1-isopropyl-1,4-diazabicyclo[2.2.2]octan-1-ium with sodium tetrafluoroborate and hexafluorophosphoric acid, respectively. Differential scanning calorimetry measurements detected that 1 and 2 underwent reversible phase transitions, which were confirmed by dielectric measurements. Single crystal X-ray diffraction data suggested that compound 1 changed from a high temperature phase with a space group of P6₃ to a low temperature one with a space group of P2₁/c, and that compound 2 transformed from the space group of Pbca at room temperature to P2₁/c at low temperature. Formation of hydrogen bonds and distortion of 1,4-diazabicyclo[2.2.2]octane rings may drive the transitions.