Reducion of a, B-alkynyl carbonyl compounds using SnCl2 and computational investigationof the reaction mechanism.

Abstract

The development of an efficient method for the reduction of α, β-alkynyl carbonyl compounds, is mostly important in organic synthesis, playing a crucial role in the synthesis of pharmaceuticals, pesticides, polymers, and other valuable chemicals. From the literature, no reaction was reported when tin (II) chloride (SnCl2) was used for the reduction of alkyne to alkane. The aim of this research was to investigate the reduction of conjugated α, β-alkynyl carbonyl compounds into alkanes using commercially available SnCl2 and other metal salts known to reduce the nitro group, such as iron (Fe) and zinc (Zn). Our approach to the synthesis of 1-(6-nitroquinoxaline2-yl)hex-1-yn-3-one 17, involves the use of 6-nitroquinoxalin-2-yl-benzenesulfonate 34 as a substrate for Sonogashira cross coupling with terminal alkyne to give appreciable yield of 1-(6-nitroquinoxalin-2-yl)hex-1-yn-3-ol 35, followed by oxidizing using PCC or Jones reagent to give 1-(6-nitroquinoxalin-2-yl)hex-1-yn-3-one 17. The oxidised product was used to optimise the reduction reaction at different temperatures (˚C), time (hours), and equivalences of SnCl2. Our first desired product 19 was obtained with yields ranging from 18 - 47%, with alkyne and nitro reduced to alkane and amine respectively when using 5 equivalents of SnCl2. During the optimisation, compound 17 also produced compound 36 with yields ranging from 45-80% with only reduced alkyne to alkane and nitro remaining unchanged, when number of equivalences of SnCl2 were reduced to 2 eq. We then introduced the oxidised compound 42 since it contains chloride instead of the nitro and we manage to reduce the alkyne to afford compound 43 with yields ranging from 55-73%. The optimised conditions were extended to other α, β-alkynyl carbonyl compounds such as 1(pyrazine-2-yl)hex-1-yn-3-one 46, 1-(pyrimidine-2-yl)hex-1-yn-3-one 51 and 1(pyridine-2-yl)hex-1-yn-3-one 55. All the compounds 46, 51, successfully reduced to give the corresponding alkanes (47 & 48, 52, 56). After successful reduction of all the compounds mentioned above using SnCl2, we then introduced other reducing agents such as iron (Fe) and Zinc (Zn) powder, following different methods from the one of SnCl2, they were able to reduce the alkyne from 42 into the alkane 43 and gave the excellent yield of 65-100% when using Zn powder and range of 60-96% when using Fe powder. However, when we introduce compound 17, the reduction took place only on the nitro instead of alkyne.

Computational studies were carried out to understand the mechanism involved at a molecular level in a relevant ethyl acetate solvent. Geometric optimisation calculations have been performed in gaseous phase by employing density functional theory-based code gaussian with RB3LYP/6-311++G (d. p) basis set. Geometrical, thermodynamical, and molecular orbitals have been calculated to investigate structural and chemical behaviour of the molecules. Among the investigated pyrazine derivatives in gaseous phase, compound 46 was found to have highest negative energy value of -24.866 Hartree/atom with short bond length between C10≡C11 of 1.195 Å as compared to compound 47 and 48. The results revealed that compound 48 has a superior stability and lower chemical reactivity as compared to compound 46 and 47, since its corresponding energy gap between HOMO (-0.32937) and LUMO (0.17780) is lager, having Egap = 0.15157 eV.