Reductive Amination of Aldehydes and Ketones ..
When MX was treated with 3-phenylpropylamine under conditions of reductive amination, five membered ring lactam 14 was isolated in 50% yield. Formation of these lactams was similar to the reductive amination of mucochloric acid as previously reported. These results suggested that in biological systems, 1 or 2 would react with nucleophilic bases pair (DNA or aminoacids) to form a Schiff base as the first step and then propagate subsequent modifications ().In conclusion a facile synthesis of MX has been developed with an overall yield of 27% in six steps, starting with 9.
Studies on Direct and Indirect Reductive Amination Procedures 1
This account documents our recent progress in exposing some of the potential of mucohalic acids in synthetic applications. Understanding their stability and reactivity in different reaction media allows the development of mild and regioselective methods to access various substituted butenolides, butenolactams, and 4,5-dihalopyridazin-3(2)-ones and to create other novel, multifunctionalized building blocks.
Hydroxyhalofuranones form a group of genotoxic disinfection byproduct (DBP) of increasing interest. Among them, mucohalic acids (3,4-dihalo-5-hydroxyfuran-2(5H)-one, MXA) are known mutagens that react with nucleotides, affording etheno, oxaloetheno, and halopropenal derivatives. Mucohalic acids have also found use in organic synthesis due to their high functionalization. In this work, the alkylation kinetics of mucochloric and mucobromic acids with model nucleophiles aniline and NBP has been studied experimentally. Also, the alkylation mechanism of nucleosides by MXA has been studied in silico. The results described allow us to reach the following conclusions: (i) based on the kinetic and computational evidence obtained, a reaction mechanism was proposed, in which MXA react directly with amino groups in nucleotides, preferentially attacking the exocyclic amino groups Over the endocyclic aromatic nitrogen atoms; (ii) the suggested mechanism is in agreement with both the product distribution observed experimentally and the mutational pattern of MXA; (iii) the limiting step in the alkylation reaction is addition to the carbonyl group, subsequent steps occurring rapidly; and (iv) mucoxyhalic acids, the hydrolysis products of MXA, play no role in the alkylation reaction by MXA.