Potential synthetic adaptogens: IV. Synthesis and study of basicity of new <Emphasis Type="Italic">N</Emphasis>-[(adamantan-1-yl)methyl]aniline derivatives

Aiming at purposeful designing new conformationally labile bromantane analogs we performed experimental and theoretical evaluation of the basicity of new and formerly prepared compounds of this series. The connection was established between the chemical structure and the basicity of compounds obtained and preferred structures were determined for subsequent biological investigations.     

Synthesis of adamantane functional derivatives basing on <Emphasis Type="Italic">N</Emphasis>-[(adamantan-1-yl)alkyl]acetamides

A series of new polyfunctional derivatives was synthesized with use of N-[(adamantan-1-yl)alkyl]-acetamides as a starting material. The reactions were carried out in acid media. The obtained compounds could be considered as a building blocks for the synthesis of conformationally restricted peptidomimetics.     

Synthesis and properties of symmetrical <Emphasis Type=Italic>N</Emphasis>,<Emphasis Type=Italic>N</Emphasis>'-Bis(R-adamantan-1-yl)ureas as target-oriented soluble epoxide hydrolase (sEH) inhibitors

Self-condensation of substituted adamantan-1-yl isocyanates in THF in the presence of DBU afforded 91–96% of symmetrical ureas as target-oriented soluble epoxide hydrolase (sEH) inhibitors. The described reaction avoids the use of the corresponding amine as counterpart. The obtained ureas are characterized by reduced melting points and improved solubility in water.     

Synthesis of pyrrolidine and tetrahydroazonine derivatives from <Emphasis Type=Italic>N</Emphasis>-[bis(ethoxycarbonyl)methyl]tetrahydropyridinium bromide and methyl acetylenedicarboxylate

The reaction of N-methyl-N-(diethoxycarbonyl)methyltetrahydropyridinium bromide with dimethyl acetylenedicarboxylate in the presence of triethylamine at room temperature afforded 1,2-dimethyl 1-ethyl 2-[(3-vinyl-1-methyl-3-phenyl-2-ethoxycarbonyl)pyrrolidin-2-yl]-ethene-1,1,2-tricarboxylate in 25% yield. Its structure was proved by XRD analysis. At cooling to −20°C the pyrrolidine yield signifi cantly decreased and 3,4-dimethyl 2,2-diethyl 1-methyl-7-phenyl-1,5,8,9-tetrahydro-2H-azonine-2,2,3,4-tetratcarboxylate was obtained in 31% yield.     

Syntheses proceeding from <Emphasis Type=Italic>N</Emphasis>-(oxiran-2-ylmethyl)-<Emphasis Type=Italic>N</Emphasis>-ethylaniline

The preparation of N-(oxiran-2-ylmethyl)-N-ethylaniline was developed. The compound was used in the synthesis of new N-derivatives of aromatic amines containing vicinal aminoalcohol moieties.     

Formation of pyrrolinium derivatives in the bromination reaction of <Emphasis Type=Italic>N</Emphasis>,<Emphasis Type=Italic>N</Emphasis>-dipropargyl ammonium salts

Bromination of ammonium salts containing two propargyl groups afforded bromine-substituted derivatives of pyrrolinium salts. The reactions of piperidinium and morpholinium analogs resulted in spirocyclic ammonium salts.     

Synthesis of 3-acetyl-6-(<Emphasis Type=Italic>o</Emphasis>-methyl benzoyl)-<Emphasis Type=Italic>N</Emphasis>-ethylcarbazole

3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole was prepared through successive o-methyl benzoylation and acetylation of N-ethylcarbazole in one pot. The overall yield was 85.6% and the structure was confirmed by ¹H-NMR and ¹³C-NMR. A preliminary investigation had also been carried out on the mechanism of the o-methyl benzoylation of N-ethylcarbazole.     

Reactions of 1-bromo-1-nitro-3,3,3-trichloropropene with <Emphasis Type=Italic>O</Emphasis>- and <Emphasis Type=Italic>N</Emphasis>-nucleophiles

Reactions of 1-bromo-1-nitro-3,3,3-trichloropropene with alcohols, benzidine and o-, m-, and p-phenylenediamines was investigated and the reaction conditions were developed. The alkoxylation and amination products and an unusual nitrogen-containing bis-aziridine were obtained; their structures were characterized by the spectral (IR, ¹H, ¹³C NMR, HMQC, and HMBC) methods.     

Regioselective <Emphasis Type=Italic>N</Emphasis>-alkylation of (2-chloroquinolin-3-yl) methanol with <Emphasis Type=Italic>N</Emphasis>-heterocyclic compounds using the Mitsunobu reagent

The Mitsunobu reaction is a well-established fundamental reaction and has been widely applied in organic synthesis. In this paper, under Mitsunobu conditions dehydration proceeds between (2-chloroquinolin-3-yl)methanol and nitrogen heterocyclic compounds such as quinazolinone, pyrimidone, 2-oxoquinoline in dry THF in the presence of triethylamine, triphenylphosphane and diethyl azodicarboxylate to give the corresponding products. As part of our recent research, we attempted to couple two N-heterocyclic compounds under Mitsunobu reaction conditions to provide efficient building blocks for natural product synthesis.     

Synthesis of aryloxyacetaldehydes and <Emphasis Type=Italic>N</Emphasis>-(aryloxyethyl)cyclohexanamine hydrochloroides

Oxidation of 2-(aryloxymethyl)oxiranes with periodic acid gave a series of aryloxyacetaldehydes which reacted with cyclohexylamine in THF, and subsequent reduction of Schiff bases thus obtained with sodium tetrahydridoborate resulted in the formation of the corresponding secondary amines which were isolated and characterized as hydrochlorides.     

Synthesis and structure of <Emphasis Type=Italic>N</Emphasis>-(2-silatranylethyl)pyrazoles

Organosilicon pyrazole derivatives containing a 2-siltranylethyl fragment on the nitrogen atom were synthesized, and their structural and stereoelectronic parameters were determined by X-ray analysis and ¹H, ¹³C, and ²⁹Si NMR spectroscopy. The nature of interaction between the pyrazole and silatrane fragments was studied.