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.     

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 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.     

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.     

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.     

Formation of Isomeric 3-Azabicyclo[3.3.1]nonanes in a Reaction of 1-(2-Hydroxyethoxy)-2,4-dinitrobenzene with Sodium Borohydride,Formaldehyde, and Methylamine

Anionic hydride adduct of 1-(2-hydroxyethoxy)-2,4-dinitrobenzene was brought into a double Mannich condensation with formaldehyde and methylamine to furnish a mixture of isomeric 3-azabicyclo[3.3.1]nonanes: 3-methyl-6-(2-hydroxyethoxy)-1,5-dinitro-3-azabicyclo[3.3.1]non-6-ene and 3-methyl-6,6-ethylenedioxy-1,7-dinitro-3-azabicyclo[3.3.1]nonane. By means of NMR spectroscopy, X-ray difraction analysis, and quantum chemistry (PM3) we demonstrated that the spirocyclic isomer had chair-chair conformation with diequatorial orientation of substituents in positions 3 and 7.     

Reduction of 3-(2-hydroxyethyl)-1,5-dinitro-3-azabicyclo[3.3.1]non-6-ene

Reduction of the nitro groups in 3-(2-hydroxyethyl)-1,5-dinitro-3-azabicyclo[3.3.1]non-6-ene was studied. The structures of the reaction products were confirmed using ¹H and ¹³C NMR spectroscopy.     

3-Azabicyclo[3.3.1]nonane Derivatives: IX. Synthesis and Molecular Structure of 3-Azabicyclo[3.3.1]nonane-1,5-diamines in Solution and in Solid State

During catalytic reduction with hydrogen on nickel of a series of 3-substituted 1,5-dinitro-3-azabicyclo-[3.3.1]non-6-enes alongside nitro groups reduction occurred also hydrogenation of the double bond. New diamines of the 3-azabicyclo[3.3.1]nonane series were synthesized, and their structure was established by means of IR, ¹H and ¹³C NMR spectroscopy and X-ray diffraction study.     

Synthesis of N-substituted 9-[2-(3,4-methylenedioxyphenyl)-2-oxoethyl]-1,5-dinitro-7,8-benzo-3-azabicyclo[3.3.1]non-7-en-6-ones

Aminomethylation has been accomplished of the anionic Yanovskii adduct of 2,4-dinitronaphthol and 3,4-dimethylenedioxyacetophenone. The structure of the 3-substituted 9-[2-(3,4-methylenedioxyphenyl)-2-oxoethyl]-1,5-dinitro-7,8-benzo-3-azabicylo[3.3.1]non-7-en-6-one was determined by two-dimensional homo-and heteronuclear correlation spectroscopy. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1382–1389, September 2007.     

Reactions of 8-methyl-5-methylsulfanylmethyl-3-thiabicyclo-[3.3.1]non-7-en-6-one at the carbonyl group

The reduction of 8-methyl-5-methylsulfanylmethyl-3-thiabicyclo[3.3.1]non-7-en-6-one with aluminum hydride, lithium tetrahydridoaluminate, or lithium tris(tert-butoxy)hydridoaluminate in tetrahydrofuran gave 8-methyl-5-methylsulfanylmethyl-3-thiabicyclo[3.3.1]non-7-en-6-ol. 8-Methyl-5-methylsulfanylmethyl-3-thiabicyclo[3.3.1]nonan-6-ol was obtained by reduction of the title compound with sodium tetrahydridoborate in pyridine or dimethylformamide. The reaction of 8-methyl-5-methylsulfanylmethyl-3-thiabicyclo[3.3.1]non-7-en-6-one with hydroxylamine hydrochloride afforded the corresponding oxime.     

Synthesis of pyrazole- and thiazole-annulated 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes

The previously unknown 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole or thiazole rings were synthesized by the reductive cyclization of m-dinitroindazoles and benzothiazoles. The method is based on the reduction of carbon-carbon bonds in the benzene ring, which are activated by the meta-nitro groups, with NaBH₄ followed by the Mannich reaction with formaldehyde and primary amines.     

Aminomethylation by Formaldehyde and Primary Amines of Anionic σσ-Adduct Obtained from 2,4-Dinitrophenol and Acetophenone Carbanion

By condensation of 2,4-bis(aci-nitro)-3-(2-phenyl-2-oxoethyl)cyclohex-5-en-1-one with formaldehyde and primary amines a series of N-substituted 9-(2-phenyl-2-oxoethyl)-1,5-dinitro-3-azabicyclo[3.3.1]non-7-en-6-ones was synthesized. With the use of X-ray analysis the cyclohexenone fragment in the 3-(2-bromoethyl)-1,5-dinitro-9-(2-phenyl-2-oxoethyl)-3-azabicyclo[3.3.1]non-7-en-6-ones was established to exist in sofa conformation, and the nitrogen-containing ring to have the chair conformation with equatorial orientation of substituents in 3 and 9 positions. The regio- and stereoselectivity of the reaction under study was interpreted relying on the quantum-chemical calculations by AM1 and PM3 procedures.     

VI. Synthesis of Heterocyclic Analogs of γ-Aminobutyric Acid from 3,5-Dinitrobenzoic Acid

A series of 7-carboxy-3-R-1,5-dinitro-3-azabicyclo[3.3.1]non-6-enes was synthesized by reduction of 3,5-dinitrobenzoic acid with sodium borohydride followed by Mannich reaction with formaldehyde and primary amines. The mechanism of decomposition under electron impact of the 3-azabicyclo[3.3.1]nonane was established. Enthalpies of formation of compounds synthesized were calculated by semiempirical PM3 method.     

Synthesis of 3-R-1,5-dinitro-3-azabicyclo[3.3.1]nonanes fused to azoles

3-R-1,5-Dinitro-3-azabicyclo[3.3.1]nonanes fused to the pyrazole, thiazole, and triazole rings were synthesized by reductive cyclization of meta-dinitrobenzazoles.     

Substituierte 9-Oxabicyclo[4.2.1]- und 9-Oxabicyclo[3.3.1]nonane III. neue ergiebige synthese von 2, 7-dioxatwistan und endo-2-hydroxy-9-oxabicyclo[3.3.1]nonen-(6)

Iodine cleavage of the [3.3.1]-iodomercuri compound 4 , easily prepared from cis, cis-cyclooctadiene-(1,5) by oxymercuration of the monoepoxide 1 (→ 3 ) followed by treatment with potassium iodide, leads to three isomeric iodides 6, 7 , and 8 , the [3.3.1]-exo-iodo isomer 8 being the predominant product. Intramolecular substitution in 8 opens an attractive new route to unsubstituted 2,7-dioxatwistane ( 19 ) [2], whereas dehydrohalogenation of 7 and 8 yields the unsaturated alcohol 17 [2], a suitable starting material for the preparation of substituted 2,7-dioxatwistanes [2], 2,7-dioxaisotwistanes ( e ) [2], and 2,8-dioxa-homotwistbrendanes ( f ).     

Design of 7-substituted 3-azabicyclo[3.3.1]non-6-enes based on allylboron-acetylene condensation

Russian Chemical Bulletin - An efficient synthesis of 7-substituted 3-azabicyclo[3.3.1]non-6-enes from available 3-borabicyclo[3.3.1]non-6-enes, the products of allylboron-acetylene condensation,...     

Synthesis of arylamino-substituted pyrazolo[3,4-d][1,2,4]triazolo[4,3-a]pyrimidinones,pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones,and their thermal isomerization

The reaction of 1-(4-oxo-1-R-5H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-arylthiosemicarbazides with methyl iodide gave rise to 1,2,4-triazolo-pyrazolopyrimidinones of linear structure, and with dicyclohexylcarbodiimide the products had angular and linear structure. The heating of compounds obtained higher than their melting point resulted in their isomerization into 7-aryl-amino-1-R-1,8-dihydro-4H-pyrazolo[3,4-d]-[1,2,4]triazolo[1,5-a]pyrimidin-4-ones.     

Heteroadamantanes and their derivatives. 9. Synthesis of 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane and derived 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes

Heating 1,5-dinitro-3,7-di(tert-butyl)-3,7-diazabicyclo[3.3.1]-nonane with concentrated hydrobromic acid gives 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane. Cyclization of the latter with various aldehydes and ketones gave a series of 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes. The behavior of the synthesized compounds under electron impact has been studied.For Communication 8 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 538–542, April, 1990.     

Racematspaltung und Bestimmung der absoluten Konfiguration von 2, 6-disubstituierten Bicyclo [3.3.1]nonanen

Resolution and Determination of the Absolute Configuration of 2,6-Disubstituted Bicyclo[3.3.1]nonanes (±)-endo, endo-Bicyclo [3.3.1]nonane-2,6-diol was resolved via diastereomeric camphanic acid esters. Conversion of the (+)-enantiomer 2 via (+)- 5 and (+)- 6 as key intermediates gave (+) methyl 3-(3-oxocyclohexyl)-propionate ( 7 ) which independently could be prepared also from the known (+)-(R)-3-oxo-cyclohexane-carboxylic acid ( 8 ). These chemical correlations establish the absolute configuration of (+) -2 , (+) -5 and (+) -6 as well as that of (+)-bicyclo [3.3.1]nonane-2,6-dione ( 1 ) obtained by oxidation of (+) -2 . The chiroptical properties of 1 and 6 are discussed.