Synthesis of betaines from 1,4-diaza[2.2.2]bicyclooctane

Betaine formation occurs on reacting 1,4-diaza[2.2.2]bicyclooctane with acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid, and 4-acrylamido-4-methyltetrahydrothiophene-1,1-dioxide-3-sulfonic acid. Various products such as monobetaines, their salts, or dibetaines may be obtained in the reaction with acrylic acid depending on the solvent and the reactant ratio. With an excess of diamine reaction occurs more rapidly with sulfonic acids, but with a deficiency of diamine reaction occurs more rapidly with the carboxylic acid.Dzerzhinsk Branch, Novgorod State Medical University, Dzerzhinsk 606007, Russian. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 547–550, April, 1998.     

1,4-Diazabicyclo[2.2.2]octanes

1,4-Diazabicyclo[2.2.2]octane-2-carboxylic acid bis(methylbromide), which is readily converted with splitting out of hydrogen bromide to the corresponding quaternary betaine, was synthesized.     

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.     

1,4-Diazabicyclo[2.2.2]octanes (review)

The literature data and our own experimental data on the synthesis and physical and chemical properties of 1,4-diazabicyclo[2.2.2]octanes as compared with their 4-deaza analogs (quinuclidines) are correlated. Methods for the practical utilization of the diazabicyclic systems are examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 723–738, June, 1976.     

Crystal structures of 1,4-diaza bicyclo[2.2.2.]octane and N,N-dimethyl formamide adducts of copper acetate

The crystal structures of copper acetate adducts with 1,4-diaza bicyclo [2.2.2.]octane and N,N-dimethyl formamide are shown to be dimeric with CuCu distances of 2.633 Å and 2.616 Å respectively.     

Catalytic synthesis of pyrazine, piperazine, and 1,4-diaza[2,2,2]-bicyclooctane

A study is made of the deamination of diethylenetriamine over acidalkali catalysts, i. e., kaolin and alumina with promoters. Promoters which raise the acidity of the catalyst, affect the formation of triethylene diamine favorably. Increasing the amount of additive increases the amount of triethylenediamine, and cuts the optimum temperature at which it is formed. On kaolin or Al₂O₃+15% B₂O₃, the yield of triethylenediamine amounts to 30% theory. Addition of MoO₃ facilitates dehydrodeamination and hydrogenolysis of the diethylenetriamine. The optimum promoter for preparing pyrazine is MoO₃ along with a small amount of acid oxides. On the Al₂O₃+5% MoO₃+1% P₂O₅, the pyrazine yield is 27.5% theory. Triethylenediamine can be separated from mixtures of it with piperazine by azeotropic distillation with mxylene or a mixture of mesitylene and -memylnaphthalene.     

Catalytic synthesis of pyrazine,piperazine, and 1,4-diaza[2,2,2]-bicyclooctane

A study is made of the deamination of diethylenetriamine over acidalkali catalysts, i. e., kaolin and alumina with promoters. Promoters which raise the acidity of the catalyst, affect the formation of triethylene diamine favorably. Increasing the amount of additive increases the amount of triethylenediamine, and cuts the optimum temperature at which it is formed. On kaolin or Al₂O₃+15% B₂O₃, the yield of triethylenediamine amounts to 30% theory. Addition of MoO₃ facilitates dehydrodeamination and hydrogenolysis of the diethylenetriamine. The optimum promoter for preparing pyrazine is MoO₃ along with a small amount of acid oxides. On the Al₂O₃+5% MoO₃+1% P₂O₅, the pyrazine yield is 27.5% theory. Triethylenediamine can be separated from mixtures of it with piperazine by azeotropic distillation with mxylene or a mixture of mesitylene and α-memylnaphthalene.     

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.     

Conformation perturbation of p-sulfonatocalix[5]arene via complexation of 1,4-diazabicyclo[2.2.2]octane

A novel conformation of p-sulfonatocalix[5]arene has been established in the solid state with two calixarenes organised in a 'bis-molecular capsule' shrouding two di-protonated DABCO molecules and two water molecules within.     

The 1,4-diaza[2.2.2] Bicyclooctane—hydrogen peroxide complex as a source of anhydrous hydrogen peroxide: the preparation of bis(trialkylsilyl) peroxides

The hazard and inconvenience of storing and handling concentrated hydrogen peroxide can be avoided by using instead the solid $\text{1}\text{2}$ complex which 1,4-diazabicyclo[2.2.2] octane forms with hydrogen peroxide, it reacts with trialkylchlorosilanes to give bis(trialkylsilyl) peroxides in good yield.     

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.     

Quaternary ammonium salts of bis-3-azatricyclo[5,3,0,11,5]undecane

The reaction of the anhydride of exo-cis-bicyclo[3,3,0]octane-2,4-dicarboxylic acid with ammonia followed by the reduction of the resulting imide with lithium aluminum hydride has yielded 3-azatricyclo[5,3,0,1^1,5]undecane, from which a number of quaternary bisammonium salts have been obtained with dihaloalkanes. These salts have also been synthesized from the anhydride of exo-cis-bicyclo[3,3,0] octane-2,4-dicarboxylic acid and polymethylenediamines.     

THE EFFECT OF 1,4-DIAZABICYCLO[2.2.2]OCTANE ON THE RADIOSENSITIVITY OF BACTERIA

Abstract— Hydroxyl radicals ('OH) are scavenged by 1,4-diazabicyclo[2.2.2]octane (DABCO) at a diffusion-controlled rate of 1.25 ± 0.1 × 10⁹ M ^-1s^-1. Unlike other efficient 'OH scavengers which exhibit protection of bacteria against irradiation both in oxic and hypoxic conditions, DABCO has been shown to protect Serratia marcescens and various strains of Escherichia coli only in oxic conditions.
DABCO appears to eliminate a component of the sensitization afforded by oxygen in all strains of E. coli tested. The level of this protection increases from ∼15% in the wild type AB 1157 to ∼100% in the recA uvrA mutant AB 2480. It is suggested that DABCO protects against lethal events that can occur on macromolecules other than DNA such as the cell membrane.
Results with added glycerol, as well as work in D₂O solution, indicate that DABCO is more likely to be acting by scavenging radicals rather than by quenching ¹O₂. If ¹O₂ is a component of the sensitization afforded by oxygen, then it is unlikely to be formed in a hydrophilic environment in the cell.     

DABCO-directed self-assembly of bisporphyrins (DABCO=1,4-diazabicyclo[2.2.2]octane)

Three isomeric zinc bisporphyrins have been prepared by covalently linking together two aminoporphyrins with an isophthalic acid derivative. The porphyrins differ in the substitution pattern on the meso phenyl groups, that is, ortho, meta, or para. Titrations carried out by UV-visible and 1H NMR spectroscopy have been used to map out the stabilities and the stoichiometries of the complexes formed with 1,4-diazabicyclo[2.2.2]octane (DABCO) in chloroform. The ortho- and meta-substituted bisporphyrins form 1:1 intramolecular sandwich complexes. The para-substituted bisporphyrin cannot adopt the cofacial conformation required for this type of complex and forms a higher order 2:2 intermolecular assembly, which is stable over a wide range of DABCO concentrations.     

Supramolecular catalytic systems based on alkylated diquaternary 1,4-diazabicyclo[2.2.2]octane derivatives

The micellization and catalytic properties of the diquaternary 1,4-diazabicyclo[2.2.2]octane derivatives, viz., 1-alkyl-4-ethyl-1,4-diazoniabicyclo[2.2.2]octane dibromides (DAD) in water were studied by conductometry, viscosimetry, and spectrophotometry. The critical micelle concentrations and the semiaxial ratio of the micellar aggregates were determined. The character and strength of the effect of the DAD micelles on the alkaline hydrolysis of 4-nitrophenyl alkylchloromethylphosphonates depend on the surfactant and substrate structures, DAD concentration in solution, and temperature. An increase in the hydrophobicity of DAD and phosphonate increases the efficiency of catalysis.     

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.     

Synthesis of fluorinated 2,6-heptanediones and 2-oxa-6- azabicyclo[2.2.2]octanes from 1,4-dihydropyridines

Electrophilic fluorination of Hantzsch-type 1,4-dihydropyridines with Selectfluor^® led to the formation of new fluorinated 2,6-heptanediones - dialkyl 2,4-diacetyl-2,4-difluoro-3-phenylpentanedioates. Novel 2,6-heptanedione derivatives in reaction with hydrazine hydrate easily form 6-amino-4,7-difluoro-3-hydroxy-1,3-dimethyl-5-oxo-8-phenyl-2-oxa-6-azabicyclo[2.2.2]octanes instead of the corresponding diazepine derivatives. The obtained 2-оxa-6-azabicyclo[2,2,2]octanes are thermally stable at the temperatures below 50°С. At higher temperatures rearrangement of 2-oxa-6-azabicyclo[2,2,2]octanes offers new fluorine-containing pyrazolinone derivatives - alkyl esters of 2-fluoro-2-((4-fluoro-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)-3-oxobutanoates.