Bogumila Rachwal

The chemistry of N-substituted benzotriazoles. Part 5. Reactions of benzotriazole with aldehydes and thionyl chloride—formation of (benzotriazol-1-yl)-1-chloroalkanes and bis(benzotriazolyl)alkanes

Reaction of benzotriazole with an excess of aliphatic aldehydes and thionyl chloride in refluxing chloroform gives the corresponding 1-(benzotriazol-1-yl)-1-chloroalkanes. Products with an α-hydrogen next to the chlorine-bearing carbon atom gradually eliminate hydrogen chloride with time or when heated. Nucleophilic displacements of the chlorine atom are described. Reaction of 2 mol equiv. of benzotriazole with 1 mol equiv. of aromatic or aliphatic aldehydes and an excess of thionyl chloride yields the corresponding bis(benzotriazol-1-yl)methylarenes and 1,1-bis(benzotriazol-1-yl)alkanes respectively; usually some of the corresponding 1-(benzotriazol-1-yl)-1-(benzotriazol-2-yl)alkanes are also formed. The 1-(benzotriazol-1-yl)-1-chloro-1-arylmethanes spontaneously react further to give bisbenzotriazolyl compounds.

The chemistry of N-substituted benzotriazoles. Part 2. Reactions of benzotriazole with aldehydes and aldehyde derivatives. 1-(α-Hydroxyalkyl)-, 1-(α-alkoxyalkyl)-, and 1-(α-acyloxyalkyl)benzotriazoles

Benzotriazole reacts readily with a variety of aldehydes to yield crystalline 1:1 adducts characterized by strong hydrogen bonding. Corresponding 1-(α-alkoxyalkyl)benzotriazoles are formed in the presence of alcohols, and 1-(α-acetoxyalkyl) analogues result from aldehyde diacetoxy derivatives. The products of more complex reactions between benzotriazoles and unsaturated aldehydes are elucidated.

The chemistry of benzotriazole. Part 3. The aminoalkylation of benzotriazole

1-(1-Hydroxyalkyl)benzotriazoles convert a wide variety of aromatic and heteroaromatic primary amines into their mono N-[1-(benzotriazol-1-yl)alkyl] derivatives in high yield. Aliphatic primary amines frequently give bis-derivatives. Product structure is established by 13C n.m.r.; dangers in the use of 1H n.m.r. to distinguish 1- and 2-substituted benzotriazoles are pointed out.

Synthesis of deuterated dexanabinol, a nonpsychotropic cannabinoid with neuroprotective properties

The deuterium labeled form of dexanabinol, a potential neuroprotective agent, was synthesized by coupling the deuterated 5-(1,1-dimethylheptyl)resorcinol, obtained in a 5-step procedure, with 4-hydroxymyrtenyl pivalate, followed by deprotection.Copyright

The chemistry of N-substituted benzotriazoles. Part 4. A novel and versatile method for the mono-N-alkylation of aromatic and heteroaromatic amines

Mono-N-alkylation of aromatic and heteroaromatic amines is achieved in high yield by NaBH4 reduction of the adducts formed from benzotriazole, aliphatic aldehydes and the amines. Reaction of the same adducts with Grignard reagents gives N-(secondary alkyl)arylamines. Carboxy groups need no protection and nitro groups are unaffected. Adenine is mono-N-alkylated in high yield.

Addition of benzotriazole to vinyl ethers. Chemistry of the adducts

Benzotriazole adds readily to ethyl vinyl ether, to 2,3-dihydrofuran, and to 3,4-dihydro-2H-pyran to form the respective α-benzotriazolyl ethers. Reactions of benzotriazole with α-methoxy derivatives of tetrahydrofuran and tetrahydropyran give similar products by substitution of benzotriazolyl for the methoxy groups. The corresponding adducts of benzotriazole and vinyl acetates are unstable and eliminate acetate anion to form geminal bis(benzotriazolyl)alkanes. The products show benzotriazol-1-yl to -2-yl isomerization. α-Benzotriazolyl derivatives of tetrahydrofuran and tetrahydropyran react with phenyl- and alkynyl-magnesium reagents to give the respective α-phenyl or α-alkynyl cycloethers. Alkylmagnesium halides by contrast attack the benzotriazolyl N-3 atom of these adducts and open the tetrahydropyranyl ring with formation of an N,N′-disubstituted o-phenylenediamine. 1H and 13C NMR spectra of the products are discussed.