N,N-bis-(dimethylfluorosilylmethyl)amides of N-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and in silico studies

Nikolin, Alexey A.; Kramarova, Eugenia P.; Shipov, Alexander G.; Baukov, Yuri I.; Negrebetsky, Vadim V.; Arkhipov, Dmitry E.; Korlyukov, Alexander A.; Lagunin, Alexey A.; Bylikin, Sergey Yu.; Bassindale, Alan R. and Taylor, Peter G. (2016). N,N-bis-(dimethylfluorosilylmethyl)amides of N-organosulfonylproline and sarcosine: synthesis, structure, stereodynamic behaviour and in silico studies. RSC Advances, 2016(79) pp. 75315–75327.

DOI: https://doi.org/10.1039/c6ra14450k

Abstract

(O→Si)-Chelate difluorides R₃R₂NCH(R₁)C(O)N(CH₂SiMe₂F)₂ (9a–c, R₁R₂ = (CH₂)₃, R₃ = Ms (a), Ts (b); R₁ = H, R₂ = Me, R₃ = Ms (c)), containing one penta- and one tetracoordinate silicon atoms were synthesized by silylmethylation of amides R₃R₂NCH(R₁)C(O)NH₂, subsequent hydrolysis of unstable intermediates R₃R₂NCH(R₁)C(O)N(CH₂SiMe₂Cl)₂ (7a–c) into 4-acyl-2,6-disilamorpholines R₃R₂NCH(R₁)C(O)N(CH₂SiMe₂O)₂ (8a–c) and the reaction of the latter compounds with BF₃·Et₂O. The structures of disilamorpholines 8a,c and difluoride 9a were confirmed by an X-ray diffraction study. According to the IR and NMR data, the O→Si coordination in solutions of these compounds was weaker than that in the solid state due to effective solvation of the Si–F bond. A permutational isomerisation involving an exchange of equatorial Me groups at the pentacoordinate Si atom in complexes 9a–c was detected, and its activational parameters were determined by ¹H DNMR. In silico estimation of possible pharmacological effects and acute rat toxicity by PASS Online and GUSAR Online services showed a potential for their further pharmacological study.