One-step synthesis of substituted 3,5-dinitropiperidines and 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonanes from 1,3-dinitropropanes

1,5-Dinitro-3,7-diazabicyclo[3.3.1]nonane derivatives were synthesized in up to 83%yields by the Mannich reaction of 1,3-dinitropropanes with excess formaldehyde and primary amines. In some cases, for instance, when 2,2-dimethyl-1,3-dinitropropane and benzylamine or monoethanolamine are used, the reaction occurs with low yields or stops at the step of formation of 3,5-dinitropiperidines. The influence of the structure of the starting compounds and reaction conditions on the yields of 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonanes and 3,5-dinitropiperidines was studied.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 405–411, February, 2005.     

Study of the bromination of 1,5-dinitro-3-azabicyclo-[3.3.1]non-6-enes

The electrophilic addition of bromine to 3-substituted 1,5-dinitro-3-azabicyclo[3.3.1]non-6-ene in carbon tetrachloride is accompanied by intramolecular 3,7-cyclization with the formation of 6-bromo-3-R-1,5-dinitro-3-azonia-tricyclo[3.3.10^3,7]nonane tribromides. In the bromination of 1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes containing substituents at the double bond, molecular complexes of halogen with the substrate were obtained. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 862–873, June, 2008.     

Chlorination features of 1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes

The electrophilic chlorine addition to 3-substituted 1,5-dinitro-3-azabicyclo[3.3.1]-non-6-enes in the tetrachloromethane is accompanied at an intramolecular 3,7-cyclization giving 6-chloro-3-R-1,5-dinitro-3-azoniatricyclo[3.3.1.03,7]nonane chlorides. The reaction of the tricyclic quaternary ammonium salts with sodium methoxide leads to the formation of dealkylated and dehydrohalogenated products, 3-substituted 8-chloro-1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes, bicyclic products with a halogen atom in an allyl position with respect to the double bond.     

Synthesis and transformations of polyhedral compounds. Synthesis of 2-[quinolin-3(2)-yl]-1,3-diazaadamantanes

A number of new 1,3-diazaadamantane derivatives containing quinoline fragments on C² have been synthesized by condensation of 1,5-dialkyl-3,7-diazabicyclo[3.3.1]nonan-9-one, 1,5-dimethyl-3,7-diazabicyclo-[3.3.1]nonan-9-ol, and 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde, 2-chloro- and 2-iodoquinoline-3-carbaldehyde, and quinoline-2-carbaldehyde.     

Facile Preparation of 3,7-Diazabicyclo[3.3.0]octane and 3,7,10-Triheterocyclic [3.3.3]Propellane Ring Systems from 1,5-Diazacyclooctane 3,7-Derivatives(1)

The cyclodimerization of p-toluenesulfonamide and 3-chloro-2-(chloromethyl)-1-propene to prepare N,N'-bis(p-toluenesulfonyl)-3,7-bis(methylene)-1,5-diazacyclooctane (1a) and its ozonation to the corresponding 3,7-dione 2a are reported. Unusual transannular cyclizations initiated by lithium aluminum hydride treatment or bromination of 1a and oxidative coupling of the dioxime derived from 2a are described. These reactions lead, respectively, to the following derivatives of the little-studied 3,7-diazabicyclo[3.3.0]octane ring system: 1,5-dimethyl-3,7-diazabicyclo[3.3.0]octane (5), N,N'-bis(p-toluenesulfonyl)-1,5-bis(bromomethyl)-3,7-diazabicyclo[3.3.0]octane (8), and N,N'-bis(p-toluenesulfonyl)-1,5-dinitro-3,7-diazabicyclo[3.3.0]octane, (12). Acid-catalyzed hydration of 1a, in contrast, gives the expected 5-methyl-3,7-diazabicyclo[3.3.1]nonan-1-ol (10). Reaction of the dibromide 8 with the nucleophiles, sodium sulfide, sodium oxide, and sodium p-toluenesulfonamide conveniently delivers the corresponding novel 3,7,10-triheterocyclic [3.3.3]propellanes.     

Synthesis,crystal and molecular structure of 3,7-ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonane

3,7-Ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonane has been found to adopt a chair–chair conformation in the crystalline state in contrast to 3,7-ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one, which had been previously found to exist in a chair-boat conformation.     

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.     

Selective reduction of 6-substituted 1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes

Reduction of 6-substituted 1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes gives either saturated 1,5-diamino-3-azabicyclo[3.3.1]nonane or unsaturated 1,5-diamino-3-azabicyclo[3.3.1]non-6-enes, depending on the conditions and nature of substituent in the substrate.     

Synthesis of new functionalized 3,7-diazabicyclo[3.3.1]nonanes by aminomethylation of the Guareschi imides

The aminomethylation of 4,4-dialkyl-2,6-dioxopiperidine-3,5-dicarbonitriles (Guareschi imides) was studied for the first time. When the Guareschi imides were treated with primary aliphatic amines and an excess of formaldehyde, 2,4-dioxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitriles were obtained in varying yields (15–67%). The structure of 9,9-dimethyl-7-(2-methylpropyl)-2,4-dioxo-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile was studied by X-ray diffraction analysis.     

Synthesis and conversions of polyhedral compounds. 25. Synthesis and convepsions of certain oxindole derivatives of 1,3-diazaadamantane and 3,7-diazabicyclo[3.3.1]nonane

By the reaction of 1,5-dimethyl-9-oxo-3,7-diazabicyclo[3.3.1]nonane with isatin and a number of its derivatives, spiro(1,3-diazaadamantane-2,3′-oxindoles) have been synthesized. In the case of 5-bromoisatin, either 3-(3-hydroxyoxindolyl)-3,7-diazabicyclo[3.3.1]nonane or the corresponding spirane is obtained, depending on the temperature. The interaction of these products with acetic anhydride has been studied. For communication 24, see [1]. A. L. Mndzhoyan Institute of Fine Organic Chemistry, Academy of Sciences of the Republic of Armenia, Erevan 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1490–1493, November, 1997.     

Synthesis and structure of new 3,7-diazabicyclo[3.3.1]nonane derivatives

Aminomethylation of triethylammonium 4-aryl-3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridin-2-olates and their sulfur and selenium analogs, as well as the structure of formed products, were studied in details. The reaction is of general character and leads to the formation of 7-substituted 9-aryl-2,4-dioxo-, 9-aryl-4-oxo-2-thioxo-, 9-aryl-4-oxo-2-selenoxo-3,7-diazabicyclo[3.3.1]nonane derivatives or their salts. The structures of ethyl 9-(2-chlorophenyl)-5-cyano-7-(4-methylphenyl)-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1-carboxylate (as a complex with N-methylmorpholine) and triethylammonium salt of 7-benzyl-4-oxo-2-selenoxo-9-(2-thienyl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile were studied by X-ray crystallography.     

Synthesis and study on 2,4,6,8-tetraaryl- 3,7-diazabicyclo[3.3.1]nonanes and their derivatives

1-Carbethoxy-2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1] nonan-9-ones (1, 2) were synthesized and their 1H and 13C NMR data are reported. Chemical shifts and spectral assignments for 2,4,6,8-tetrakis(4-chlorophenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (3), 2,4,6,8-tetraphenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one (4) and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonanes (5-7) are also included.     

Complex formation of copper(II) and palladium(II) with L,L-3,7-bis[2-(4-hydroxyphenyl)-1-(methoxycarbonyl)ethyl]-1,5-di(ethoxycarbonyl)-3,7-diazabicyclo[3.3.1]nonan-9-one

Complexation of copper(II) chloride, copper(II) triflate, and palladium(II) chloride with optically active L,L-3,7-bis[2-(4-hydroxyphenyl)-1-(methoxycarbonyl)ethyl]-1,5-di(ethoxycarbonyl)-3,7-diazabicyclo[3.3.1]nonan-9-one was studied.     

Structure of 3,7-Diazabicyclo[3.3.1]nonane Complexes as the Basis of Creating New Metallocyclic Supramolecular Ensembles

The molecular and crystal structure of the complex of cupric bromide with 1,5-diphenyl-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ones was studied. The geometry of the complexes of bispydines with cupric halides was shown to depend on the substituent at the nitrogen atom.     

Synthesis and Reactions of Polyhedral Compounds. 27. Development of a Synthetic Route for 2- Spiro-substituted 6-Hydroxy-5,7-dimethyl-1,3-diazaadamantanes

Alternative methods for the synthesis of 2-spiro-substituted 6-hydroxy-5,7-dimethyl-1,3-diazaadamantanes have been developed. These are the reduction of the ketone group to hydroxyl in the corresponding 6-oxo-1,3-diazaadamantanes and the condensation of 9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane (obtained by different routes from 5,7-dimethyl-6-oxo-1,3-diazaadamantane) in reaction with cyclic ketones.     

Synthesis and Structure of Derivatives of 9-(2-Oxopropyl)-1,5-dinitro-7,8-benzo-3-azabicylo[3.3.1]non-7-en-6-ones

A number of 3-R-9-(2-oxopropyl)-1,5-dinitro-7,8-benzo-3-azsbicyclo[3.3.1]non-7-en-6-ones was synthesized by Mannich reaction involving Yanovsky adduct of 2,4-dinitronaphthol. It was established by molecular spectroscopy and X-ray diffraction analysis that the piperidine ring in these compounds was in the chairconformation with a diequatorial position of the substituent attached to the heteroatom and 2-oxo-propyl group, and the cyclohexenone fragment was in sofaform. By an example of 3-methyl-9-(2-oxopropyl)-1,5-dinitro-7,8-benzo-3-azsbicyclo[3.3.1]non-7-en-6-one the dissociative ionization of bicyclononanes under the electron impact was investigated.     

3-Azabicyclo[3.3.1]nonane Derivatives: IV. Synthesis of Amino Acids with 3-Azabicyclo[3.3.1]nonane Fragment

A series of 1.5-dinitro-3-azabicyclo[3.3.1]non-6-enes was prepared by reduction of 1-R-2,4- and 1-R-3,5-dinitrobenzenes with potassium borohydride followed by Mannich reaction with formaldehyde and amino acids. The molecular structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid was studied by X-ray diffraction analysis. The mechanism of decomposition under electron impact was determined for (7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid.     

Synthesis of 3,7-diacyl-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane derivatives as promising lipid bilayer modifiers

Novel 3,7-bis(dialkylaminoacetyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonanes were synthesized, which can undergo conformational reorganization under the change of solvent polarity, protonation (the change of pH) or complexation with LaCl₃. These compounds are capable of being embedded into the liposomal membranes and can serve as molecular switches for the development of stimulus-sensitive liposomal containers.     

Synthesis,structural and conformational study of some amides derived from 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide

A series of 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carbonitrile and 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide N-substituted have been synthesized and studied by ¹ H and ¹³C nmr spectroscopy and the crystal structure of 3,7-dimethyl-9-benzylamino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide dihydrochloride ( IVb· 2HCl) has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform, dimethyl sulfoxide-d₆ and methanol-d₄ the same preferred flattened chair-chair conformation with the methyl groups in equatorial position. The carboxamido group lies in a plane nearly perpendicular to the bispidine skeleton. The conformation and protonation sites of IVb· 2HCl in the crystal state and in deuterium oxide solution are discussed.     

3-Azabicyclo[3.3.1]nonane Derivatives: V. Synthesis of 7-Polyfluoroalkoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes

A number of 7-polyfluoroalkoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes were synthesized by reduction of 3,5-dinitrophenyl polyfluoroalkyl ethers with sodium tetrahydridoborate, followed by the Mannich reaction with formaldehyde and primary amines.