Several transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane

The transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane (I) were studied. The dichloride of 9-(-chloroethyl)-3,9-diazabicyclo[3.3.1]nonane, which is readily cyclized in the basic form to 3,9-diazatricyclo[3.3.1.2^3,9]undecane (V), was synthesized by reduction of I with LiAlH₄ and debenzylation with subsequent replacement of the hydroxy group, in the alcohol formed, by chlorine. An unusual cleavage of the carboxymethyl residue to form the nitrogen-unsubstituted dichloride of 3,9-diazabicyclo[3.3.1]nonane (XI) occurs on treatment with thionyl chloride of the acid obtained by saponification and debenzylation of I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1372–1375, October, 1970.     

Syntheses and conversion of polyhedral compounds. 26. Synthesis of new heteropolyhedral compounds by heterocyclization of certain 3,7-disubstituted derivatives of 3,7-diaza-and 1,3,7-triazabicyclo-[3.3.1]nonanes

The following heterocyclization reactions have been carried out: heterocyclization of 3,7-diacryloyl-3,7-diazabicyclo[3.3.1]nonane by benzylamine, heterocyclization of 3,7-diacryloyl-, 3,7-bis(-bromopropionyl)-, and 3,7-bis(-chloroethyl)-3,7-diazabicyclo[3.3.1]nonanes by hydrogen sulfide, and heterocyclization of 3,7-bis(bromoacetyl)- and 3,7-diacryloyl-1,3,7-triazabicyclo[3.3.1]nonanes by benzylamine and hydrogen sulfide. New compounds were obtained, based on previously unknown thiadiaza-, triaza-, and tetraazatricyclic systems.For Communication 25, see [1].A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Erevan 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1133–1136, August, 1998.     

Synthesis and conversions of polyhedral compounds 20. Synthesis of certain derivatives of 3,7-diazabycyclo[3.3.1]nonane

1,3-Diazaadamantanes containing hydrogen atoms or a hydroxyl or oxime group at C₍₆₎, under the action of 2 moles of aralkyl halides, are converted in alkaline aqueous media to 3,7-diaralkyl-3, 7-diazabi cyclo(3.3.1]nonanes containing the indicated groups at C₍₉₎. Analogously, quaternary salts of 1,3-diaza-adamantanes containing hydrogen atoms or a hydroxyl group at C₍₆₎ are converted in an alkaline aqueous medium to the corresponding 3-alkyl-3,7-diazabicyclo[3.3.1]nonanes containing the indicated groups at C₍₉₎.For Communication 19, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 401–406, March, 1994.     

Synthesis and structure of 7-alkoxyalkyl-3-thia-7-zabicyclo[3.3.1]nonan-9-ones and several of their derivatives

New 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones were synthesized by the double Mannich cyclization of tetrahydrothiopyran-4-one with suitable alkoxyalkylamines and paraformaldehyde in acetous methanol. Wolff-Kishner decarbonylation of these bicyclic ketones gave 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonanes. The reduction of 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones by alkali metal hydride complexes leads to a mixture of two stereoisomeric secondary alcohols, which are epimers at C₍₉₎. Active analgesic, antiarrhythmic, and antibacterial compounds were found among these products. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 585–592, April, 2006.     

5-Hydroxy-1-phosphabicyclo[3.3.1]nonan

5-Hydroxy-1-phosphabicyclo[3.3.1]nonane A new approach to 1-phosphabicyclo[3.3.1]nonane compounds involves free-radical cyclization of 4-trimethylsilyloxy-4-phosphinomethyl-hepta-1.6-diene synthesized by the reaction of 2.2-diallyl-oxirane with KPH₂ followed by trimethylsilylation. Trimethylsilyl groups are easily cleaved in boiling methanol forming 5-hydroxy-1-phosphabicyclo[3.3.1]nonanes. Silylated and desilylated bicyclic compounds are characterized by n.m.r. and i.r. data.     

Rigid Scaffolds: Synthesis of 2,6-Bridged Piperazines with Functional Groups in all three Bridges

The activity of pharmacologically active compounds can be increased by presenting a drug in a defined conformation, which fits exactly into the binding pocket of its target. Herein, the piperazine scaffold was conformationally restricted by substituted C₂- or C₃-bridges across the 2- and 6-position. At first, a three-step, one-pot procedure was developed to obtain reproducibly piperazine-2,6-diones with various substituents at the N-atoms in high yields. Three strategies for bridging of piperazine-2,6-diones were pursued: 1. The bicyclic mixed ketals 8-benzyl-6-ethoxy-3-(4-methoxybenzyl)-6-(trimethylsilyloxy)-3,8-diazabicyclo[3.2.1]octane-2,4-diones were prepared by Dieckmann analogous cyclization of 2-(3,5-dioxopiperazin-2-yl)acetates. 2. Stepwise allylation, hydroboration and oxidation of piperazine-2,6-diones led to 3-(3,5-dioxopiperazin-2-yl)propionaldehydes. Whereas reaction of such an aldehyde with base provided the bicyclic alcohol 9-benzyl-6-hydroxy-3-(4-methoxybenzyl)-3,9-diazabicyclo[3.3.1]nonane-2,4-dione in only 10 % yield, the corresponding sulfinylimines reacted with base to give N-(2,4-dioxo-3,9-diazabicyclo[3.3.1]nonan-6-yl)-2-methylpropane-2-sulfinamides in >66 % yield. 3. Transformation of a piperazine-2,6-dione with 1,4-dibromobut-2-ene and 3-halo-2-halomethylprop-1-enes provided 3,8-diazabicyclo[3.2.1]octane-2,4-dione and 3,9-diazabicyclo[3.3.1]nonane-2,4-dione with a vinyl group at the C₂- or a methylene group at the C₃-bridge, respectively. Since bridging via sulfinylimines and the one-pot bridging with 3-bromo-2-bromomethylprop-1-ene gave promising yields, these strategies will be exploited for the synthesis of novel receptor ligands bearing various substituents in a defined orientation at the carbon bridge     

The Pauson-Khand reaction as a new entry to the synthesis of bridged bicyclic heterocycles: application to the enantioselective total synthesis of (−)-alstonerine

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alkaloid (−)-alstonerine.     

Mass-spectrometric study of physiologically active β-thiosemicarbazones of N-alkylisatins

The molecular ions of isatin (I) and N-methyl- (II) and N-ethylisatin (III) -thiosemicarbazones undergo fragmentation via many pathways with the elimination of NH₃, H₂S, CO, CH₂N₂, CHN₃, CH₂N₂S, CH₂NS, and CHNS particles; this is due to primary localization of the charge on the heteroatoms of the thiosemicarbazone residue. A previously unknown rearrangement, which consists in migration of an HS group to the -carhon atom of the heteroring with subsequent ejection of a CHN₃ fragment. The [M — CO]⁺ ions undergo fragmentation with the elimination of CH₂N₂S; in the case of II and III fragmentation is preceded by detachment of a hydrogen atom (II) or a methyl group (III) from the substituent attached to the ring nitrogen atom. The [M — CO, -H, -CH₂NS]⁺ (II) and [M — CO, -CH₃, -CH₂N₂S]⁺ (III) ions undergo fragmentation with the ejection of HCN in two ways through both the ring nitrogen atom and the thiosemicarbazone residue. Schemes for the principal pathways of fragmentation and rearrangements are presented. The compositions of the ions were confirmed by the high-resolution mass spectra and the mass spectra of the N-deuteroalkyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 1979.     

Molecular and crystal structure of 3,7-di(2-propenyl)-1,5-diphenyl-3,7-diazabicyclo[3.3.1]-nonan-9-one complexed with copper(II) chloride

We have investigated the molecular and crystal structure of 3, 7-di(2-propenyl)-1, 5-diphenyl-3, 7-diazabicyclo[3.3.1]nonan-9-one complexed with copper(II) chloride. We have shown for the first time that the reason for the distortion of the coordination polyhedron of the metal is the interaction of the substituents at the nitrogen atoms with the halogen atoms.Communication 2 in the series Complexing properties of 3,7-diazabicyclo[3.3.1]nonanes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 770–774, June, 1996. Original article submitted April 13, 1996.Deceased.     

Study of the Steric Structure of 7-Alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and Their Derivatives Using 1H NMR Spectroscopy

Using the ¹H NMR spectroscopic method it has been shown that 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonanes exist in deuterochloroform solution in a double chair conformation. 7-(3-Butoxypropyl)-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol is a 1:1 mixture of the two stereoisomeric alcohols. One of them exists in a double chair conformation having an equatorial hydroxyl group with relation to the piperidine ring and the other in a chair-boat conformation having an axial hydroxyl group which involves an intramolecular hydrogen bond with the unshared electron pair of the nitrogen atom.     

Efficient Synthesis of a New Family of 2,6-Disulfanyl-9-selenabicyclo[3.3.1]nonanes

The efficient synthesis of a new family of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes in high yields has been developed based on 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion generated from bis-isothiouronium salt of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane. The derivatives of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonane containing alkyl, allyl and benzyl moieties have been prepared in 90–99% yields by nucleophilic substitution of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion with alkyl, allyl and benzyl halides. The reaction of nucleophilic addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to alkyl propiolates afforded 2,6-di(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonanes. The conditions for regio- and stereoselective addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to a triple bond of alkyl propiolates have been found. To date, not a single representative of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes has been described in the literature.     

Synthesis and structure of 2,5,7,10-tetramethyl-2,4,8,10-tetraazabicyclo[4.4.0]decane-3,9-dione

2,5,7,10-Tetramethyl-2,4,8,10-tetraazabicyclo[4.4.0]decane-3,9-dione, a regioisomer of the previously known 2,5,7,8-tetramethyl-2,4,8,10-tetraazabicyclo[4.4.0]decane-3,9-dione, has been synthesized, and its structure has been established by X-ray diffraction analysis. The bicyclic system of this molecule is formed by two heterocyclescis-annelated through the C(1)-C(6) bond. The relative configurations of the asymmetric centers areS for C(5), andR for C(7). In the monohydrate crystal studied, the molecules are linked by O...H-O_w and O...H-N type H-bonds forming a three-dimensional framework.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 136–138, January, 1995.     

The mass-spectral fragmentation of bicyclo[3.3.1]nonanes

The mass spectra of twelve bicyclo[3.3.1]nonanes have been recorded. The high number of metastables observed, exact mass measurements of the ions and low ionising voltage spectra, permitted the rationalisation of most of the fragmentation pathways. The 1-phenyl substituent triggers the major fragmentation in the hydrocarbon, whereas it has minor influence in the oxygenated compounds. Significant differences in the abundance of [M ? H₂O]⁺ ions for stereoisomeric alcohols of this series have been observed.     

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.     

Steric and electronic properties in bicyclic phosphines. Crystal and molecular structures of Se = Phoban-Q (Q = C2, C3Ph, Cy and Ph)

Reacting a series of the bicylic Phoban-Q (9-Q-9-phosphabicyclo[3.3.1]nonane and 9-Q-9-phosphabicyclo[4.2.1]nonane) derivatives (Q = alkyl, cyclo alkyl, aryl) with KSeCN results in the formation of the corresponding phosphine selenides. The first order phosphorus-selenium coupling constants, ¹J_P-Se, ranges from 682 to 689 Hz for the [3.3.1] isomers and from 703 to 717 Hz for the [4.2.1] isomers indicating the former to be significantly more electron rich. The crystal structures of Se = Phoban[3.3.1]-Q (Q = CH₂CH₃, C₃H₆Ph, Cy, and Ph) and Se = Phoban[4.2.1]-Q (Q = Cy and Ph) are reported and reveal PSe bond distances ranging from 2.1090(9) to 2.1245(7) Å. For Q = Cy and Ph the two isomers ([3.3.1] and [4.2.1]) co-crystallise in the same crystal enabling the determination of the molecular structures for both from the same data collection. The cone angles for all ligand derivatives were determined according to the Tolman model but by using the actual P-Se bond distances and were found to be virtually identical ranging from 165° to 175°. Changes in the Q substituent have a minor effect on the overall steric and electronic properties of the Phoban family of ligands and can be used to manipulate physical properties without changing the chemical properties significantly.     

Formation pathways and structure—Property interrelationship of 3-imino-1-methyl-5,5-dialkyl-4,7,7-tricyano-2-oxabicyclo-[2.2.1]heptane derivatives

The problems of the structure—property interrelationship of 3-imino-2-oxabicyclo[2.2.1]heptane derivatives are discussed on the basis of x-ray diffraction studies (XDS). A pathway for the formation of the bicyclic compounds is proposed, and the realization of spirans in the reaction of sym-tetracyanoethane with conjugated cyclic systems containing s-cis C=C and C=O fragments is substantiated. The factors responsible for the syn orientation of the oxygen atom and the N-substituent of the imino group are analyzed. It is shown that a change in the steric hindrance in the bicyclic compounds leads to a change in the conformation of the latter. The reasons for the shortening of the C_sp3-C_sp3, C_sp3-C_sp and C=N exo bonds and the correlation of the XDS and IR spectroscopic data are examined. From the XDS data for N-bromo-substituted imines, a model for Br⁺...NC electrophilic attack was proposedCommunication 16 from the series Chemistry of 1,1,2,2-tetracyanoethane. See [1] for Communication 15.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 519–526, April, 1991.     

3- Substituted 3- Azabicyclo[3.3.1]nonan- 9- ols and Their Transformations Involving the Hydroxy Group

The reduction of 3-benzyl- and 3-tert-butoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-ones with sodium tetrahydridoborate gave the corresponding alcohols as mixtures of á- and ä-epimers at a ratio of 2: 3. The resulting alcohols reacted with acetyl chloride and methanesulfonyl chloride at the hydroxy group to form O-acetyl and O-methylsulfonyl derivatives. Reactions of the latter with potassium iodide and sodium azide afforded 3-substituted 9-iodo(azido)-3-azabicyclo[3.3.1]nonanes. 9-Iodo derivatives were treated with triphenylphosphine to obtain triphenylphosphonium salts which were converted into the corresponding phosphonium ylides by the action of sodium methoxide in methanol, and the ylides readily reacted with benzaldehyde according to Wittig.     

Anchimerically assisted redox reactions : Comparisons of the effect of transannular - OH and -NH2 group son the rate of the aqueous I2 oxidation of thioethers. Structures of the heteroatom bridged l-thioniabicyclo[3.3.1]nonane intermediates

The rate law for the aqueous I₂ oxidation of 5-amino-1-thiacyclooctane has been determined and compared with 5-hydroxy-l-thiacyclooctane. The crystal structures of the 9-aza- and 9-oxa-l-thioniabicyclo[3.3.1]nonanes formed on oxidative cyclization are compared.     

1H NMR study on the inclusion of bicyclo[3.3.1]nonanes in cyclodextrins

- and -cyclodextrins were found to form 1:1 inclusion complexes with 2,6- and 2,9-substituted bicyclo[3.3.1]nonanes. The binding constants and the structure of the complexes were estimated from titration studies and 2D ROESY experiments.     

Aminomercuration intramoleculaire d'aziridines cycloocteniques et de leurs aminoalcools precurseurs

N-substituted cyclooctenic aziridines undergo intramolecular mercuration with mercuric salts; after reduction, N-substituted 9-azabicyclo[3.3.1]- and [4.2.1]nonanes are isolated. Mercuration of amino alcohols (precursors to aziridines) leads to the same products but with different yields dependent on the mercuric salt used. In some cases, aziridinium salts are intermediates in basic medium from the organo mercuric compounds during reduction. Extension of this reaction is studied with two aliphatic models.