This article describes an efficient method for solution-phase parallel synthesis of 2-quinoxalinol salen Schiff-base ligands. The novelty of this article is the synthesis of a new category of ligands using Schiff-base condensation of an aldehyde with a diaminoquinoxaline.
The synthesis of 2- quinoxalinol salen ligand consists of two key steps. First the diamino-2- quinoxalinol is prepared by employing a sequence of five reaction steps and it starts with commercially available difluorodinitrobenzene (DFDNB). In the second key step, 2-quinoxalinol is reacted with an aldehyde to make Schiff-base ligands. Moderate to excellent yields (41 % - 86 %) have been reported in the preparation of these ligands.
This paper was used as a reference to synthesize ligand 6cd. To achieve this, diamino-2- quinoxalinol 4c was first prepared starting with 10 mmol of DFDNB. All five steps ran smoothly and yellow crystals of compound 4c were obtained in 57 % yield as it describes in the article. However, the crystallization step of 2-quinoxalinol can take 48 h-72 h. But it was found that, 2- quinoxalinol can be easily separated by column chromatography with hexane:ethyl acetate as eluent to get pure compound 4c in 70 % yield. This provides a better yield of 2-quinoxalinol 4c than the reported yield of 58 % and pure compound can be separated out within 2 h-3 h rather than waiting for 48 h-72 h.
Next, compound 4c (0.1 mmol) was reacted with 10 equivalents of 3,5-di-tert- butylsalicylaldehyde to give a yellow color Schiff-base ligand in 56 % yield after 48 h. However, this step could have been efficient if an acid catalyst was used. Therefore, above reaction was performed by reacting 1 equivalent of 4c and 2.5 equivalents of 3,5-di-tert-butylsalicylaldehyde in the presence of 5 mol % trifluoroacetic acid to make 6cd in 60 % yield after 18 h. Not only this modified condition reduced the required amount of aldehyde to 2.5 equivalents, but also it cut down the reaction time to 18 h.
In summary, reproducibility of the reactions described in the article has been excellent. Some steps can be improved to make the overall synthesis more efficient as explained in this review.