Open AccessSynthesis and structure of new derivatives of 2-chloro-N-(3-R-1,5-dinitro-8-oxo-3-azabicyclo[3.3.1]non-6-en-7-yl)acetamides
Author(s) -
Loik G. Mukhtorov,
Е. В. Иванова,
Maria B. Nikishina,
Irina V. Shahkeldyan,
Yury Atroshchenko,
M.B. Karimov,
К. И. Кобраков
Publication year - 2019
Publication title -
butlerovskie soobŝeniâ
Language(s) - English
Resource type - Journals
ISSN - 2074-0212
DOI - 10.37952/roi-jbc-01/19-57-3-83
Subject(s) - chemistry , acetamide , sodium hydride , organic chemistry , adduct , medicinal chemistry , semicarbazide , mannich reaction , catalysis
The production of new 3-azabicyclononane derivatives is an important trend in the synthesis of organic compounds. It is known that 3-azabicyclononane is a key pharmacophore of a number of plant alkaloids that are widely used in medicine (aconitin, quinidine, tropane, cocaine, garnet, etc.). Among synthetic heterocycles containing a 3-azabicyclo[3.3.1]nonane fragment, compounds with various types of biological activity were found: analgesic and anti-inflammatory, antimicrobial and fungicidal, anti-cancer, antioxidant, etc. We synthesized a number of new derivatives of 3-azabicyclo[3.3. 1]nonane by Mannich condensation of hydride σ-adduct 2-chloro-N-(2-hydroxy-3,5-dinitrophenyl)acetamide with formaldehyde and primary amines or amino acids. The synthesis was carried out in two stages. In the first stage, under the action of sodium tetrahydride borate on a solution of 2-chloro-N-(2-hydroxy-3,5-dinitrophenyl)acetamide, the C=C bonds of the aromatic ring were reduced to form a 3-charge hydride adduct. The resulting diaduct was isolated from the solution and, while cooling with ice, was introduced into Mannich condensation with formaldehyde and a solution of the primary amine or amino acid. When the reaction mixture was acidified with dilute orthophosphoric acid to pH 4-5, precipitates of the target products precipitated. After recrystallization from ethanol, the yield of the target products, depending on the substituent at the nitrogen atom, was 75-90%. This method is distinguished by relative simplicity, availability of reagents and allows under mild conditions to transfer from the aromatic system activated by nitro groups to 3-azabicyclo[3.3.1]nonane derivatives, containing promising from the point of view of further functionalization nitro, carbonyl, amino groups, and also halogen atom . The structure of the compounds obtained was proved by IR, 1H-, 13C-, two-dimensional correlation NMR spectroscopy, as well as high-resolution mass spectrometry data (HRMS).