Chemistry of N-halamines. XIII. Amination of adamantanes and their precursors with trichloramine-aluminum chloride

Abstract

The reaction of trichloramine and aluminum chloride with adamantane and alkyladamantanes gave excellent yields of the corresponding bridgehead amines. Various tricyclic alkanes upon treatment with trichloramine under Friedel-Crafts conditions underwent rearrangement and amination in one step to the corresponding aminoadamantanes. This represents the first case in which rearrangement of an adamantane precursor is accompanied by the introduction of a functional group. Synthetically, the trichloramine amination route provides a simple, one-step method of obtaining aminoadamantanes in high yields. The postulated mechanism involves hydride abstraction by positive chlorine from the adamantane nucleus. Subsequent attack by a nitrogen-containing nucleophile affords the , -dichloro derivative which has been isolated. Acid hydrolysis effects conversion to the amine. This laboratory has reported the direct amination of aromatic compounds with N-halamines under Friedel-Crafts conditions leading to basic products of unusual orientation. Thus, when monoalkylbenzenes were allowed to react with trichloramine and aluminum chloride, the corresponding m-alkylanilines were formed.4-7 The proposed addition-elimination mechanism, substitution, accounts for the selective meta orientation. Similar results were obtained with dialkylbenzenes,8 biphenyl,9 and naphthalene9 as substrates.When p-cymene was aminated with trichloramine and aluminum chloride, the presence of 8-amino-p-cy-mene10 in the product stimulated investigation of other aryldialkylmethines in relation to side-chain attack. The efforts were rewarding since various para-substituted alkylbenzenes which possess a tertiary hydrogen afforded the corresponding f-carbinamines.11-13 Further studies showed that alkanes reacted in an analogous fashion, e.g., 1 -methylcyclohexane yielded 1-amino-1 -methylcyclohexane in good yield.14The object of the present work was to investigate amination in the adamantane series in relation to the synthetic and mechanistic aspects. Since 1-aminoadamantane possesses antiviral properties,16 additional (1) Paper XIII: Chemistry of N-Halamines.

Steric Hindrance Underestimated: It is a Long, Long Way to Tri-tert-alkylamines

“…13 C NMR (100.6 MHz, CDCl 3 ): δ = 20.0 (q, −CH(CH 3 ) 2 ), 29.1 (q, −C(CH 3 ) 3 ), 47. Compounds 27, 54 28, 55, 56 29, 57 31, 55 42, N,N-dichloroadamantane-1-amine, 58 1-chloro-2,2,5,5-tetramethyl-pyrrolidine, 1-chloro-2,2,5,5tetramethylpyrroline, N-tert-butyl-N-chloro-tert-amylamine, 55 Nchloro-di-tert-amylamine, and N-tert-butyl-N-chloro-tert-octylamine were analogously prepared according to reported literature. 59 N-(tert-Butyl)-N-chloro-adamantan-1-amine (42).…”

“…Compounds 27 , 28 , , 29 , 31 , 42 , N , N -dichloroadamantane-1-amine, 1-chloro-2,2,5,5-tetramethyl-pyrrolidine, 1-chloro-2,2,5,5-tetramethylpyrroline, N - tert -butyl- N -chloro- tert -amylamine, N -chloro-di- tert -amylamine, and N - tert -butyl- N -chloro- tert -octylamine were analogously prepared according to reported literature …”

“…Method I. Using N,Ndichloro-adamantan-1-amine 58 (0.50 g, 2.28 mmol), TMEDA (3.00 g, 26.20 mmol), and isopropylmagnesium chloride (2.85 mL, 2 M in THF, 5.70 mmol), the crude product was added to MeOH (15 mL), and the mixture was stirred for 5 min at 40 °C. The side product 1,2di(adamantan-1-yl)diazene was removed as a white solid by filtration (35% yield).…”

Amidation of 1-bromo-3,5-dimethyladamantane catalyzed with manganese compounds and complexes

“…Memantine is unique pharmaceutical preparation effective for the treatment of Alzheimer's disease and other CNS disorders at an early stage. It helps to normalize the psychic activity of human: it improves memory and ability to concentrate, reduces fatiguability, depression symptoms, and restores neuromuscular system disorders [1][2][3][4][5].Typically 1-bromo-3,5-dimethyladamantane I is used for laboratory and industrial synthesis of various N-(adamant-1-yl)amides by Ritter method [6,7]. Known methods for producing N-(adamant-1-yl)acylamides include reacting 1-bromoadamantane with formamide and acetamide at elevated temperature (185±195°C) [8], or in the presence of the stoichiometric amount of silver sulfate as the catalyst [9].…”

“…Memantine is unique pharmaceutical preparation effective for the treatment of Alzheimer's disease and other CNS disorders at an early stage. It helps to normalize the psychic activity of human: it improves memory and ability to concentrate, reduces fatiguability, depression symptoms, and restores neuromuscular system disorders [1][2][3][4][5].…”