Amine synthesis using tandem aza-witting/imine reduction reactions

Abstract

Nowadays, both secondary and tertiary amines are playing vital roles in modern chemical industry as well as pharmaceutical industry. Various synthetic methods of amines have also been reported due to their promising applications. In this thesis, a simple and widely applicable one-pot aza-Wittig/reduction method is reported for synthesizing both secondary and tertiary amines. Firstly, we focused on tandem aza-Wittig/reduction reactions for synthesizing secondary amines. We noticed that an aza-Wittig reaction involving an iminophosphrane which is the product from a Staudinger reaction, followed by addition of an aldehyde can be used to construct a C=N double bond in the product. By making use of the PPh3O (byproduct of aza-Wittig reactions) as the catalyst along with trichlorosilane as the reducing agent, the imine products in the aza-Wittig reactions can be converted into amines in one pot. In addition to using PPh3, highly-efficient heterogeneous polystyrene-based rasta resin-supported PPh3 was also examined in our study. Secondly, in order to broaden the utility of this one-pot method, instead of using relatively dangerous organic azides as substrates, in situ azide formation reaction was added to the flow chart. By reacting alkyl bromides with sodium azide or tertabutylammonium azide can give various azides in one-pot. Thirdly, the secondary amines formed using our one-pot procedure can undergo reductive amination reaction with aldehyde to give diverse tertiary amines as the final products in one pot. In this reaction, trichlorosilane reduction was performed twice by utilizing the phosphine oxide byproduct from the aza-Wittig reaction as a catalyst. Finally, chemistry regarding tandem one-pot aza-Wittig reaction by using catalytic amount of phosphine oxide was discussed. Instead of using organic azides, various aryl isocyanates were used as substrates for the reaction, with the help of catalytic amount of a five-membered ring phosphine oxide to give high yields of secondary amines. Chemistry studied in the thesis stands as solid proof for the superiority of our method. Tandem one-pot reactions improved the efficiency of our method by avoiding lengthy workup and purification steps. Our chemistry may serve as a good alternative for both secondary and tertiary amine synthesis in the future.