Flow Synthesis of 2-Methylpyridines via α-Methylation

Molecules

Camille Manansala¹  Geoffrey K. Tranmer¹ 

[1] College of Pharmacy, Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T6, Canada; E-Mail:

关键词: continuous flow;    2-methylpyridines;    Raney^® nickel;    green chemistry;    α-methylation;    Ladenberg rearrangement;    flow chemistry;   

DOI  :  10.3390/molecules200915797

来源: mdpi

【 摘 要 】

A series of simple 2-methylpyridines were synthesized in an expedited and convenient manner using a simplified bench-top continuous flow setup. The reactions proceeded with a high degree of selectivity, producing α-methylated pyridines in a much greener fashion than is possible using conventional batch reaction protocols. Eight 2-methylated pyridines were produced by progressing starting material through a column packed with Raney^® nickel using a low boiling point alcohol (1-propanol) at high temperature. Simple collection and removal of the solvent gave products in very good yields that were suitable for further use without additional work-up or purification. Overall, this continuous flow method represents a synthetically useful protocol that is superior to batch processes in terms of shorter reaction times, increased safety, avoidance of work-up procedures, and reduced waste. A brief discussion of the possible mechanism(s) of the reaction is also presented which involves heterogeneous catalysis and/or a Ladenberg rearrangement, with the proposed methyl source as C1 of the primary alcohol.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.