Reactivity of Cage-Like Amines toward p-Toluenesulfonyl Chloride and Diphenyl Chlorophosphate in Acetonitrile

The nucleophilic reactivity of amines of the norbornane, norbornene, and adamantane series toward ptoluenesulfonyl chloride and diphenyl chlorophosphate in acetonitrile at 25°C is determined mainly by the steric factor. Parameters characterizing spatial accessibility of the reaction center in the amine molecule have been determined. Cage-like substituents show no appreciable effect on the amine reactivity, as compared to common alkyl groups.     

Synthesis, structure, and transformations of N-(bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)-N-[(oxiran-2-yl) methyl]-arenesulfonamides

Reaction of N-(bicyclo[2.2.1]hept-5-en-endo-2-ylmethyl)arenesulfonamides with epichlorohydrin in the presence of tetramethylammonium iodide afforded a group of framework N-[(oxiran-2-yl)methyl]sulfonamides and also a series of new dioxiranes, N-(oxiran-2-yl)methyl-N-(exo-5,6-epoxybicyclo[2.2.1]heptan-endo-2-ylmethyl)arenesulfonamides. The aminolysis of N-(oxiran-2-yl)methyl]arenesulfonamides with benzylamine and benzylpiperazine led to the chemo- and regioselective opening of the epoxy ring according to Krasusky rule. The structure of compounds was established by spectral methods and the XRD analysis.     

Reactions of Bi-, Tri-, and tetracyclic amines with succinic anhydride

Succinic anhydride reacted with cage-like amines {bicyclo[2.2.1]hept-5-en-exo-and-endo-2-yl-methanamines, 2-(bicyclo[2.2.1]hept-5-en-endo-2-yl)ethanamine, exo-5,6-epoxybicyclo[2.2.1]heptan-exo-2-yl-methanamine, tetracyclo[6.2.1.1^3,6.0^2,7]dodec-9-en-endo-4-ylmethanamine, 1-(bicyclo[2.2.1]heptan-2-yl)ethanamine, and 4-azatricyclo[5.2.1.0^2,6]dec-8-ene} to give the corresponding amido acids having a cage-like fragment. The latter were converted into carboximides by the action of hexamethyldisilazane in boiling benzene in the presence of zinc(II) chloride and then into epoxy derivatives. The structure of the newly synthesized compounds was confirmed by IR and NMR spectroscopy.     

Amino Alcohols with Bicyclic Carbon Skeleton. Alternative Functionalization of Nucleophilic Reaction Centers

Electron density distribution in the molecules of stereoisomeric N-[2-(4-nitrophenyl)-2-hydroxyethyl](bicyclo[2.2.1]hept-2-en-5-ylmethyl)amines was studied by quantum-chemical methods, and their chemical transformations were examined. According to the results of PM3 semiempirical calculations, the nitrogen atom in the amino alcohols possesses greater proton affinity, as compared to the oxygen atom. Chemoselective functionalization of the amino alcohols at the nitrogen and oxygen nucleophilic centers was effected using 4-nitrobenzoyl chloride, 4-toluenesulfonyl isocyanate, and hexamethyldisilazane in the presence of chlorotrimethylsilane. N,O-Bis-acylated amino alcohols were synthesized, one of which was subjected to oxidation with peroxyphthalic acid. The oxidation was not accompanied by heterocyclization, and it led to formation of the corresponding exo-epoxynorbornane derivative with the endo-oriented substituent at the bicyclic framework. The structure of the products was confirmed by the IR and ¹H NMR spectra.     

Phase-transfer Catalysis in Alkylation of Ureas Containing Cage-like Fragments

Russian Journal of Organic Chemistry -     

Synthesis, Structure, and Derivatives of endo-4-Aminomethyltetracyclo[6.2.1.13,6.02,7]dodec-9-ene

Synthesis was performed and structure studied of endo-4-cyanotetracyclo[6.2.1.1^3,6.0^2,7]dodec-9-ene prepared by reaction of a stereochemically uniform endo-5-cyanobicyclo[2.2.1]hept-2-ene with cyclopentadiene. By analysis of potential energy surface (PES) for reactions of endo-5-cyanobicyclo[2.2.1]hept-2-ene and the respective exo-stereoisomer with cyclopentadiene (in B3LYP/6-31G(d) approximation) the endo,exo-junction and anti-orientation of the methylene bridges in the bicyclic fragments of the adducts were shown to be preferable. Reduction of the tetracyclic nitrile with lithium aluminum hydride yielded endo-4-aminomethyltetracyclo-[6.2.1.1^3,6.0^2,7]dodec-9-ene whose geometry and conformational characteristics were studied by means of molecular mechanics method. Products were obtained from reactions of the tetracyclic amine with p-toluene-, p-chloro-benzene-, p-nitrobenzenesulfonyl chlorides, p-nitrobenzoyl chloride, succinic anhydride, mesityl and p-toluene-sulfonyl isocyanates, phenyl, p-toluenesulfonyl, and benzoyl isothiocyanates, p-nitrophenyloxirane, and N-(2,3-epoxypropyl)carbazole. A series of the amine derivatives was epoxidized with perphtahlic acid. The structure of compounds synthesized was confirmed by analysis of their IR spectra, ¹H, ¹³C, and two-dimensional NMR spectra, and additionally by calculation of the chemical shifts in ¹H and ¹³C NMR spectra by procedures GIAO and CSGT in PBE1PBE/6-31G^## approximation.     

Derivatives of exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and exo-5-Aminomethyl-endo-5-methyl-exo-2,3-epoxybicyclo[2.2.1]heptane

exo-5-Aminomethyl-endo-5-methylbicyclo[2.2.1]hept-2-ene and its 2,3-epoxy derivative were synthesized, and their geometric parameters and conformational properties, in particular the barriers to rotation of the aminomethyl fragment about the exocyclic C⁵ÄC bond, were studied by the molecular-mechanics method (MMX) and compared with those found for structurally related exo-5-aminomethylbicyclo[2.2.1]hept-2-ene. The title compounds were brought into reactions with electrophilic reagents: arenesulfonyl chlorides, isocyanates, and isothiocyanates.     

Adamantyl-Substituted Amino Alcohols. Synthesis and Functionalization at the Nitrogen and Oxygen Nucleophilic Centers

1-Aminoadamantanes and 1-aminomethyladamantanes were brought into reactions with p-nitro- phenyloxirane and 9-carbazolylmethyloxirane. The reactions occurred in a regioselective fashion according to the Krasusky rule, which was confirmed by the ¹H and ¹³C NMR data. The resulting amino alcohols having a p-nitrophenyl moiety were subjected to functionalization at the nitrogen and oxygen nucleophilic centers using p-nitrobenzenesulfonyl chloride, p-nitrobenzoyl chloride, and hexamethyldisilazane, and N,O-bisacyl derivative was synthesized. The structure of the products was proved by IR and ¹H NMR spectroscopy.     

Amides containing two norbornene fragments. Synthesis and chemical transformations

Reactions of stereochemically pure bicyclo[2.2.1]hept-5-en-exo- and endo-2-ylmethylamines with bicyclo[2.2.1]hept-2-ene-5-carbonyl chlorides gave the corresponding carboxamides having two norbornene fragments. Their conformations and steric strains were studied by the MM2 molecular mechanics method, and electron density distribution in their molecules was determined by PM3 quantum-chemical calculations. The results of calculation of the energy of activation for epoxidation of the dienes in the gas phase and in solution (COSMO) showed that chemoselective oxidation of only one double bond therein is impossible. The corresponding diepoxy derivatives were synthesized by oxidation of the dienes with peroxyacetic acid; the oxidation of amides with endo orientation of the carbonyl group was accompanied by heterocyclization with formation of exo-2-hydroxy-4-oxatricyclo[4.2.1.0^3,7]nonan-5-one. Reduction of the amides and their epoxy derivatives with lithium tetrahydridoaluminate afforded the corresponding secondary amines possessing two cage-like fragments; the reduction products were functionalized at the nitrogen atom by treatment with p-nitrobenzenesulfonyl chloride and p-toluenesulfonyl isocyanate. The structure of the prepared compounds was confirmed by the IR and ¹H and ¹³C NMR spectra.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1467–1478.Original Russian Text Copyright © 2004 by L. Kasyan, Isaev, A. Kasyan, Golodaeva, Karpenko, Tarabara.     

Methods and mechanisms of epoxy compounds reduction

Analysis was performed of reduction processes of epoxy derivatives obtained from unsaturated compounds belonging to various groups: alkenes, cycloalkenes, spiroalkanes, and substituted norbornenes. The regio- and stereochemistry was discussed of reactions between epoxides and complex metal hydrides, of catalytic hydrogenation, and some other processes. The mechanisms were considered of the reduction reactions, in particular, those involving radical and ion radical intermediates.