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.     

Supramolecular systems based on 1-alkyl-4-aza-1-azoniabicyclo[2.2.2]octane bromides

The aggregation in aqueous solutions of alkylated 1,4-diazabicyclo[2.2.2]octanes of various hydrophobicity and their adsorption at the water-air interface were studied by tensiometry, conductometry, potentiometry, viscosimetry, and ESR spectroscopy. The parameters of adsorption, critical micelle concentrations, concentrations of free counterions (bromide ions), and degree of binding of the counterions with micelles were determined. The intensification of the micelle formation ability of the surfactants with an elongation of the alkyl fragment was shown. The effective radii of ensembles of the hexadecyl and octadecyl derivatives were determined by the dynamic light scattering method. A relationship between the concentration dependences of the size of micelles and their shape was established.     

Supramolecular catalytic systems based on 1, 4-diazabicyclo[2.2.2]octane,its alkylated quaternary derivatives,and lanthanum nitrate

Spectrophotometry was used to study the catalytic effects of the systems composed of N-monoand N, N-dialkylated 1, 4-diazabicyclo[2.2.2]octanes and lanthanum nitrate on the hydrolysis rate of O-alkyl O-4-nitrophenyl chloromethylphosphonates (Alk = Et, Buⁿ, and n-hexyl). The mechanism of action and efficiency of the catalytic system depend on the structure of the heterocycle, its propensity to aggregation and complexation with the lanthanum cation, and the relative content of the components in solution. The maximum catalytic effect (a ～115-fold increase in the hydrolysis rate constant) was achieved in micellar solutions of the cationic monoalkylated derivative of 1, 4-diazabicyclo[2.2.2]octane and lanthanum nitrate.

     

Alkylated 1,4-diazabicyclo[2.2.2]octanes: self-association, catalytic properties, and biological activity

Aggregation of 1-hexadecyl-4-aza-1-azoniabicyclo[2.2.2]octane bromide in the presence of diethyl 4-nitrophenyl phosphate was studied using ¹H NMR spectroscopy. The quantitative characteristics of the aggregation were determined. The data obtained were used to explain the catalytic effect of micelles on the hydrolysis of the phosphate. It was found that the aggregation properties and biological activity of alkylated mono- and dicationic 1,4-diazabicyclo-[2.2.2]octanes are correlated.     

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.     

Synthesis of anticonvulsant activity of some 2-phenylcarbamoyl-1,2-diazabicyclo[2.2.2]octanes

A number of aryl isocyanates were adducted to 1,2-diazabicyclo[2.2.2]octane and afforded 2-phenyl-carbamoyl-1,2-diazabicyclo[2.2.2]octanes. Some of the products displayed anticonvulsant activity.     

Synthesis of 1, 2-diazabicyclo [2.2.2] octane, 1, 2-diazabicyclo [3.2.1]-octane,and their derivatives

1, 2-Diazabicyclo [2.2.2] octane, its 6-methyl homolog, and 1, 2-diazabicyclo [3.2.1] octane are synthesized by a general method involving nitrosation of piperidine carboxylic acids, subsequent reduction to 1-aminopiperidine carboxylic acids, cyclization to 3-keto-1, 2-diazabicycloalkanes, reduction of the latter to 1, 2-diazabicycloalkanes. A number of 2-substituted 1, 2-diazabicyclo [2.2.2] octanes are synthesized.     

Self-assembly of symmetrical and dissymmetrical dicationic surfactants in the solid phase and in solution

The effect of the spacer structure (linear, cyclic, bicyclic) and dissymmetry of alkyl fragment in a series of dicationic gemini surfactants on the ability to form thermotropic liquid crystals and on the micellar properties was studied. Transitions crystal-thermotropic liquid crystals-isotropic solution were studied using differential scanning calorimetry and optical microscopy. The self-diffusion coefficients of micelles and monomers of the dicationic dialkyl derivatives of 1,4-diazabicyclo[2.2.2]octane in water were determined by pulsed field gradient NMR spectroscopy. The effect of the surfactant structure on the values of critical micelle concentrations, hydrodynamic radii, and aggregation numbers of micelles was analyzed.     

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.     

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.     

Complexes of 1-alkyl-4-aza-1-azoniabicyclo[2.2.2]octane bromides with lanthanum nitrate. Micelle-forming and adsorption properties

Novel organometallic surfactants were synthesized from monoquaternized 1,4-diazabicyclo[2.2.2]-octanes of varied hydrophobicity [Alk = C _n H_2n+1, n = 14, 18] and lanthanum nitrates. The spectral, micelleforming, and adsorption properties of the synthesized compounds were studied by IR, ¹Н NMR and electronic spectroscopy, tensiometry, conductometry, and potentiometry. The critical micelle concentrations, counterionic micellar binding constants, and adsorption parameters at the water–air interface were determined and compared with the respective characteristics of the ligands and conventional amphiphiles.     

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.     

Efficient Baylis-Hillman Reaction via a 1,4-Diazabicyclo[2.2.2]octane-based Ionic Catalyst

A novel ionic catalyst, 1-butyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride based on 1,4-diazabicyclo[2.2.2]octane was synthesized and applied in the Baylis-Hillman reaction, which occurred readily at room temperature to afford the corresponding adducts in good yield. The ionic catalyst could be recycled for seven runs without diminution in its catalytic activity.     

Synthesis of monomers that expand on polymerization. Synthesis and polymerization of 2,6,7-trioxabicyclo[2.2.2]octanes with phenyl groups

2,6,7-Trioxabicyclo[2.2.2]octanes with phenyl group were prepared to obtain monomers which expand on polymerization. 1-Phenyl-4-ethyl-2,6,7-trioxabicyclo[2.2.2]octane (I) could expand 0.2% during polymerization at a temperature slightly higher than the melting point. 1,4-Diphenyl-2,6,7-trioxabicyclo[2.2.2]octane (II) also expanded as much as 1.4% on polymerization. Further, the hydrolysis of 2,6,7-trioxabicyclo[2.2.2]octanes with p-substituted phenyl groups were investigated to estimate the stability in water.     

Efficient <Emphasis Type="Italic">Baylis-Hillman</Emphasis> Reaction <Emphasis Type="Italic">via</Emphasis> a 1,4-Diazabicyclo[2.2.2]octane-based Ionic Catalyst

Summary. A novel ionic catalyst, 1-butyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride based on 1,4-diazabicyclo[2.2.2]octane was synthesized and applied in the Baylis-Hillman reaction, which occurred readily at room temperature to afford the corresponding adducts in good yield. The ionic catalyst could be recycled for seven runs without diminution in its catalytic activity.     

DABCO catalyzed dimerization of α,β-unsaturated ketones and nitriles

α,β-Unsaturated ketones dimerize in the presence of catalytic amount of 1,4-diazabicyclo[2.2.2]octane(DABCO) to produce the corresponding 2-methylene-1,5-diketones in good yields. Acrylonitrile provides the corresponding dimerized product.     

Easy Conversion of Dimethyl α-(Bromomethyl)fumarate into Functionalized Allyl Ethers Mediated by DABCO

New functionalized allyl ethers were obtained in good yields following the mild selective reaction of different alcohols with allyl bromide in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) and a catalytic amount of triethylamine (TEA) at room temperature.     

Phosphorylation of polyethyleneimine in the solutions of calyx[4]resorcinolarene and its mixture with the surfactant

Phosphorylation of alkylated polyethyleneimine in chloroform in the presence of alkylated calyx[4]-resorcinolarenes with 2-hydroxyethoxy- and phosphorus-containing substituents and cetyl(3-hydroxypropyl)-dimethylammonium bromide was studied by means of the UV spectrophotometry. It was found that the character and the degree of the effect of calyxarene and its mixture with the surfactant depend on the hydrophobicity of macroring and the ratio of concentrations of components in the solution. The increase in the content of calyxarene and decrease in the concentration of polymer leads to the transformation of the catalytic action into the inhibiting one.     

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.     

The simple solvent-free synthesis of 1H-quinazoline-2,4-diones using supercritical carbon dioxide and catalytic amount of base

Only supercritical carbon dioxide (scCO₂) as a reactant and a solvent, and catalytic amount of base (DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), DBN (1,5-diazabicyclo[4.3.0]non-5-ene), Dabco^® (1,4-diazabicyclo[2.2.2]octane), and triethylamine) afforded 1H-quinazoline-2,4-diones in good to excellent yields from 2-aminobenzonitriles. 6,7-Dimethoxy-1H-quinazoline-2,4-dione, which is a key intermediate of medicines (Prazosin, Bunazosin, and Doxazosin) was synthesized successfully in a 97% yield, using 0.1 equiv of DBU under scCO₂ (10 MPa) at 80 °C.