Synthesis of 7-azabicyclo[2.2.1]heptane, exo-2-chloro-7-azabicyclo[2.2.1]heptane, and derivatives

Abstract

A synthesis of 7-azabicyclo[2.2.1]heptane (1) in five steps and an overall yield of 18 % has beenachieved. An alternative five-step route which gives 1 in 36% yield but which requires large amounts of platinum oxide has also been developed. In comparison, the only previous synthesis of this con~pound gave less than a 1 % overall yield of an impure product. Several N-acyl derivatives and the N-n~troso derivative have been prepared, and the barriers to rotation about the N-CO bond of the acetyl derivative and the N-NO bond of the nitroso derivative have been determined. The barriers were found to be 1.2 and 6.5 kcal less, respectively, than in their unstrained analogs. exo-2-Chloro-7-azabicyclo[2.2.l]heptane has also been synthesized.Canadian Journal of Chemistry, 48,2065Chemistry, 48, (1970 Considerable interest has recently developed in the nitrogen analogs of bicyclo [2.2.1 Iheptane. Reports on the synthesis and reactions of compounds containing nitrogen in the 1-position (1,2) and in the 2-position (3,4) have appeared. The 7-azabicyclo[2.2.1]heptane system has perhaps received more attention. In particular, many highly substituted derivatives have been produced by the Diels-Alder reactions of N-alkyl and N-acyl pyrroles with dimethylacetylene dicarboxylate (5-12). In contrast the parent 7-azabicyclo [2.2.1 Iheptane (1) was reported as synthesized only in impure form and was characterized by conversion to a picrate and a 7,7-dimethiodide derivative (12). Its synthesis from hydroquinone involved seven steps and gave 1 in an overall yield of less than 1 %. We wish to report an improvement in the synthesis of 1, which allows its preparation in yields of up to 36 %. The proof of structure of 1 is supported by its conversion to five derivatives, two of which are the subject of a temperature-dependent nuclear magnetic resonance (n.m.r.) investigation. In addition the exo-2-chloro derivative of 1 was synthesized and preliminary studies of its reactivity are reported.

Stereoselective hydrogenation of Paracetamol to trans-4-acetamidocyclohexanol on carbon-supported RuM (M = Co, Ni) bimetallic catalysts

“…Synthesis of trans-4-aminocyclohexanol is usually approached by catalytic hydrogenation of 4-acetamidophenol (Paracetamol) [9,[11][12][13][14][15], as shown in Fig. 1.…”

Synthesis of new 7-azabicyclo[2.2.1]heptane derivatives

“…Fraser and Swingle reported the chlorination of 7-trichloroacetyl-7-azabicyclo[2.2.1]heptane with sulfuryl chloride in the presence of benzoyl peroxide. 17 More recently, and when this work was in progress, Armstrong and co-workers reported what appears to be the first intramolecular cyclization of a precursor in this series, namely exo-2-bromo-7-(toluene-4-sulfonyl)-7-azabicyclo[2.2.1]heptane. 18 Here we report the synthesis of the conformationally constrained epibatidine analogues 3, the preparation of radical precursors 4-7 and their intramolecular free radical reactions (Figure 2).…”

Influence of modifiers on the performance of Ru-supported catalysts on the stereoselective hydrogenation of 4-acetamidophenol

“…This would simplify the workup and purification steps, minimize the negative environmental effects, and reduce the capital costs. A diversity of metals (Raney nickel, platinum oxide) have been tested in the hydrogenation of paracetamol under several conditions, giving a wide range of results in terms of selectivities to the cis and trans isomers, varying from 1:1 to 1:4 cis/trans ratios [2,4]. But, very few reports analyzing the factors that affect the reaction have been carried out until now [5,6].…”