Structural study of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol

The infrared spectra in several media and the crystal structure of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]-nonan-9β-ol ( I ) (Scheme I) have been determined, in order to complete the structural study described for the title compound from the ¹H and ¹³C nmr data [1]. The bicyclic system adopts a flattened chair-chair conformation in which the cyclohexane ring is more flattened. The methyl and phenyl groups are in equatorial positions and the OH group in an axial position with respect to the piperidine ring.     

1H Nmr stuctural analysis of N3′-dialkylaminoethyl derivatives from azabicyclospirohydantoins

Based on the data from ¹H nmr spectra, the structure and spatial conformation of the N₃′-β-dimethyl and diethylaminoethyl derivatives from 3-alkyl-3-azabicyclo[3.2.1]octane-8-spiro-5′-hydantoins and 3-alkyl-3-azabicyclo[3.3.1]nonane-9-spiro-5′-hydantoins are established. The monosubstitution on the imide nitrogen atom has also been confirmed.     

Synthesis,structural and conformational study of some esters derived from 8-phenethyl-8-azabicyclo[4.3.1]decan-10α-ol

A series of 10α-acyloxy-N-phenethyl-8-azabicyclo[4.3.1]decane derivatives have been synthesized and studied by ¹H and ¹³C nmr spectroscopy, and the crystal structure of N-phenethyl-10aL-(xanten-9″-carbonyloxy)bicyclo[4.3.1]decane 2 has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform the same preferred conformation adopted by the piperidine ring as a distorted chair conformation flattened at N-8 with both the phenethyl and acyloxy groups in the equatorial position with respect to the piperidine ring. These results are in close agreement with that found for compound 2 in the crystalline state.     

Conformational and configurational studies on 3-azabicyclo[3.3.1]nonane (3-abn) derivatives and related systems employing carbon-13 NMR spectroscopy

The ¹³C nmr spectra of 4 cis-2,4-diphenyl-3-azabicyclo[3.3.1]nonanes, 11 cis-2,4-diaryl-3-azabicyclo[3.3.1]-nonan-9-ones, 26 cis-2,4-diaryl-3-azabicyclo[3.3.1]-nonan-9-ols or acetates thereof, 5 cis-2,4-diaryl-3-azabi-cyclo[4.3.1]decan-10-ones or -10-ols and 5 cis-2,4-diphenyl-3-aza-7-thiabicyclo[3.3.1]nonan-9-ones, -9-ols or 9-yl acetates have been recorded. Except for the 7-thia compounds, which appear to exist mainly in the configuration and conformation with the nitrogen-containing ring in the boat form, these compounds seem to exist overwhelmingly in chair-chair conformations. The configuration of the 9-ols and their acetates (syn or anti to the nitrogen-containing ring) has been deduced from the spectra. In a number of cases, the structures assigned differ from those earlier postulated. Broadening of one set of aryl signals (probably those due to the ortho carbons) in the case of N-methyl (but not N-H) compounds without ortho substituents is ascribed to restricted phenyl rotation.     

Conformational analysis of 3-borabicyclo[3.3.1]nonane derivatives

Conformations of 3-borabicyclo[3.3.1]nonane derivatives have been studied by means of ¹H and ¹³C NMR spectroscopy. With the aid of the coupling constants ³J(HH) and ¹³C chemical shifts it has been shown that all the derivatives of 3-borabicyclo[3.3.1]nonane with the trigonal boron atom studied are in a flattened double-chair conformation. In 3-borabicyclo[3.3.1]nonane derivatives with the tetra-coordinated boron atom and substituents at the 7α-position, the chair-boat conformation predominates, the boat conformation being characteristic of the cyclohexane ring; exceptions are the compounds with the internal donor—acceptor bond between the boron atom an 7α-substituent.     

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,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.     

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.     

Chemistry of 3-Azabicyclo[3.3.1]nonane: II. Reduction of 6-Acetoxy-3-benzyl-1- ethoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-one with Sodium Borohydride

Reduction of 6-acetoxy-3-benzyl-l-ethoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-one with sodium borohydride was investigated in various conditions. The stereochemistry of reduction products was deduced from ¹H and ¹³C NMR and mass spectra.     

Synthesis,structural and conformational study of N-β(or γ)-acyloxyalkylnortropinones

A series of N-β(γ)-acyloxyalkylnortropinones have been synthesized and studied by ¹H and ¹³C nmr spectroscopy, and the crystal structure of N-[γ-(p-chlorophenylcarbonyloxy)propyl]nortropinone 4 has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform solution the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N-8 envelope and distorted chair conformation, puckered at N-8 and flattened at C-3 respectively, with the N-substituent in axial position with respect to the piperidone ring. These results are in close agreement with that found for compound 4 in the crystalline state.     

Synthesis, structural and crystallographic study of some carbamates derived from 9-methyl-9-azabicyclo[3.3.1]nonan-3α-ol

A series of benzimidazole, thiazole and benzothiazole carbamates derived from 9-methyl-9-azabicyclo[3.3.1]nonan-3α-ol was synthesized and studied by ¹H, ¹³C, 2D NMR and IR spectroscopy. To assist in the interpretation of the spectroscopic data, the crystal structure of 3 (9-methyl-9-azabicyclo[3.3.1]nonan-3α-yl 2-amino-1H-benzimidazole-1-carboxilate) was determined by X-ray diffraction. It has been found that 1-carbamates and 2-carbamates can be obtained in the case of the benzimidazole derivatives. The benzimidazole-1-carbamates are obtained in higher yields (41, 38%) than the benzimidazole-2-carbamates (3, 9%). The compounds studied displayed in CDCl₃ solution a preferred chair–boat conformation with the substituted ring in a distorted boat form and the N–CH₃ substituent in an axial position with respect to the chair piperidine ring. This conformation is similar to that determined by X-Ray diffraction for compound 3.     

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.     

Diels-alder reaction of 2-chloro-2-nitrosopropane with 1,3-cyclohexadiene

3-(2-Chloropropyl)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene and 2-oxa-3-azabicyclo[2.2.2]oct-5-ene hydrochloride have been prepared by cycloaddition of 2-chloro-2-nitrosopropane to 1,3-cyclohexadiene and their structure determined by nmr, using a ¹H nmr shift reagent.     

SYNTHESIS OF AND CONFORMATIONAL STUDIES ON N-ALKYL-3-THIA-7-AZABICYCLO [3.3.1]NONAN-9-ONES AND DERIVATIVES. A SINGLE CRYSTAL X-RAY DIFFRACTION ANALYSIS OF 2,2,4,4-TETRAMETHYL-6,8-DIPHENYL-3-THIA-7-AZABICYCLO [3.3.1]-NONAN-9-ONE

Abstract

A series of N-alkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones and derivatives have been prepared from the reaction of an appropriate 4-thianone, an aldehyde and an amine in a Mannich type condensation. Reduction of the ketones via Wolff-Kishner conditions produced bicyclic systems with the methylene bridging group. Addition of Grignard reagents to the ketones did yield the expected alcohols. Conformational analysis of the systems was performed via diagnosis of the ¹H and ¹³C NMR spectra. A single crystal X-ray diffraction analysis of 2,2,4,4-tetramethyl-6,8-diphenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one was accomplished and revealed a boat conformer for the nitrogen-containing ring and a chair conformer for the sulfur-containing ring. The ketone crystallized in the triclinic space group P1 (Z=2) with a=6.216 (3), b=10.507 (5), c=15.335 (6) Å, α=86.64 (4), β=86.66 (4), and γ=98.51 (5)° [Vol=986.55 ų].     

5,6-dihydropyridine: synthesis and characterization

5,6-dihydropyridine 1 is synthesized either by flash vacuum thermolysis of 1-azabicyclo[2.2.2] oct-2-ene 3 or by dehydrochlorination over solid bases of N-chloro-1,2,5,6-tetrahydropyridine 4 and characterized at low temperature by its ¹H and ¹³C nmr and ir spectra.     

Synthesis, complete NMR spectral assignments, and antifungal screening of new 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oxime derivatives

Abstract  

A series of differently substituted 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oximes have been synthesized and their ¹H and ¹³C NMR chemical shifts have been unambiguously assigned using H,H-COSY, NOESY, HSQC, and HMBC spectral data. On the basis of the NMR studies, irrespective of the nature and position of the substituents, all reported compounds exist in twin-chair conformation with equatorial disposition of the phenyl groups at C-2 and C-4 of the 3-azabicyclononane moiety. Among the synthesized oxime derivatives, compounds with halo-substituents at ortho/para positions of the phenyl showed good antifungal profile against all tested organisms.     

3,7-disubstituted bicyclo[3.3.1]nonanes—III: Synthesis and conformation of bicyclo[3.3.1]nonane-3α,7α-dicarboxylic acid,its dimethyl ester and some other 3,7-disubstituted bicyclo[3.3.1]nonanes; adamantane as an integrated holding system

The conformation of bicyclo[3.3.1]nonane-3α,7α-dicarboxylic acid and its dimethyl ester has been studied by comparing ¹H NMR and ¹³C NMR spectra of these compounds with those of some model 3,7-disubstituted bicyclo[3.3.1]nonanes, fixed in a single conformation by the use of adamantane as an integrated holding group or by means of suitable substitution. It is shown that the dicarboxylic acid and its dimethyl ester exist predominantly as two rapidly interconverting (identical) chair-boat conformations with distinctly flattened rings; the population of the double-boat conformation appears to be very small.     

Epoxidation of 2-azabicyclo[2.2.1]hept-5-en-3-one

Epoxidation of 2-azabicyclo[2.2.1]hept-5-en-3-one has been performed in high yield with potassium hydrogen persulfate at pH 6, ¹H nmr data indicate an exo stereoconfiguration of the epoxide.     

Synthesis,structural, conformational and biochemical study of some 3β-acyloxytropan-3α-carboxylic acid hydrochlorides

A series of 3β-acyloxytropan-3α-carboxylic acid hydrochlorides have been synthesized and studied by ¹H and ¹³C nmr spectroscopy, and the crystal structure of 3β-(3,4,5-trimethoxybenzoyloxy)tropan-3α-carboxylic acid hydrochloride 4c has been determined by X-ray diffraction. The compounds studied display in methanol-d₄ the same preferred conformation. The pyrrolidine and piperidine rings adopt a flattened N8 envelope and distorted chair conformation; puckered at N8 and flattened at C3 respectively with the N-substituent in equatorial position with respect to the piperidine ring. In all cases, there is only one mode (axial) of proton uptake at the piperidine nitrogen atom. These results are in close agreement with that found for compound 4c in the crystalline state. The inhibitory ability of the title compounds upon ³ H -GABA binding to sinaptosomal brain membranes is also reported.     

1H nmr structural analysis of azabicyclospirohydantoins

The structure and spatial conformation of 3-alkyl-3-azabicyclo[3.2.1]octane-8-spiro-5′-hydantoins and 8-alkyl-8-azabicyclo[4.3.1]decane-10-spiro-5-hydantoins has been determined on the basis of the data from ¹H nmr. The chair conformation of the piperidine ring and the presence of only one stereoisomer at the spiro carbon atom are corroborated. All these facts have been confirmed by x-ray diffraction methods (2).