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Open AccessCommunication

Flow Synthesis of 2-Methylpyridines via α-Methylation

1
College of Pharmacy, Faculty of Health Science, University of Manitoba, Winnipeg, MB R3E 0T6, Canada
2
Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Kerry Gilmore
Molecules 2015, 20(9), 15797-15806; https://doi.org/10.3390/molecules200915797
Received: 12 August 2015 / Revised: 20 August 2015 / Accepted: 21 August 2015 / Published: 31 August 2015
(This article belongs to the Special Issue Recent Advances in Flow Chemistry)
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. View Full-Text
Keywords: continuous flow; 2-methylpyridines; Raney® nickel; green chemistry; α-methylation; Ladenberg rearrangement; flow chemistry continuous flow; 2-methylpyridines; Raney® nickel; green chemistry; α-methylation; Ladenberg rearrangement; flow chemistry
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MDPI and ACS Style

Manansala, C.; Tranmer, G.K. Flow Synthesis of 2-Methylpyridines via α-Methylation. Molecules 2015, 20, 15797-15806.

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