Good synthesis with comments for improvement


The article presents a synthetic methodology to prepare chiral N,N-disubstituted, 1,2-diamines, which can be convenient precursors to tridentate ligands.

Particularly, I used the synthetic route using cyclohexane-1,2-diamine (both racemic and enatiopure) to obtain a series, where R=methyl. As the authors point out, no need of extensive purification steps are needed. Fairly clean products (by NMR) are obtained following the instructions.

The following comments can be useful for the reader:

To prepare compound (3) from diamine (1), the use of commercial Pinner salt gives excellent results. No need to prepare it.

The reductive amination step (5 to 7a) is a very versatile reaction, as the report presents. Particularly, I used the procedure to obtain the dimethyl derivative (7a) in quantitative yields, but also, in the research group, the use of propionaldehyde, NaCNBH3 and AcOH   (in this case, the reaction was stirred for 18h after de addition of acetic acid) and the same work up presented in the experimental section gives place to formation of the N-acetoxy-N,N-di-n-propyl cyclohexane diamine in 86% yield. The deprotection reaction, using the same stoichiometry presented in the reported procedure, just stirring the reaction for 18h, produces an 84% yield of the N, N-di-n-propylcyclohexane-1,2-diamine.

The condensation reaction between diamine (9a) and 3,5-di-tert-butyl-salicylaldehyde  to produce imine (11), was purified by recrystallization  from warm acetonitrile instead of the chromatographic purification described in the original paper, improving the yield up to 85%  and the corresponding diaminophenol (12) was recrystallized from acetonitrile. Similar procedure can be used using the n-propyl derivative. The reaction with salicylaldehyde produces 86% yield of the imine after 18 h of stirring without further work up and the formation of the diaminophenol produces  94 % yield, following the same experimental procedure reported in the original article.

The reactions pathway from (1) to (12), gives similar results in terms of yields even when the reactions were carried out using 5 g of the cyclohexyldiamine.

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