Boekelheide reaction

The Boekelheide reaction is a name reaction in organic chemistry . It is the two-step conversion of 2-methylpyridine- N -oxide to 2-hydroxymethylpyridine and analogous conversions.

It was named after the American chemist Virgil Boekelheide (1919–2003), who first published the reaction in 1954.

Overview reaction

During the reaction, 2-methylpyridine- N -oxide 1 is treated with trifluoroacetic anhydride , so that rearrangement occurs and 2-hydroxymethylpyridine 2 is ultimately obtained as the product after hydrolytic work-up :

Reaction mechanism

The following reaction mechanism is described in the literature:

A free electron pair of the negatively charged oxygen atom attaches itself to the trifluoroacetic anhydride 3 . This leads to electron rearrangement in the trifluoroacetic anhydride so that it is split. The resulting intermediate stage 4 is deprotonated in the next step and trifluoroacetic acid is split off. This creates intermediate level 5 . A [3.3] sigmatropic rearrangement of 5 leads to the trifluoroacetyl ester 6 . The subsequent hydrolysis leads to a further cleavage of a trifluoroacetic acid molecule, and 2-hydroxymethylpyridine 7 is obtained as the product .

Application examples

This reaction shows that the Boekelheide reaction does not only work with trifluoroacetic anhydride. The reaction with acetic anhydride is also possible. In addition, the reaction can be stopped earlier so that an ester is obtained as the product .

This reaction shows that not only 2-methylpyridine- N- oxide can be selected as the starting material . The reaction is also possible with other amine oxides .

Individual evidence

^ V. Boekelheide and WJ Linn: Rearrangements of N-Oxides. A Novel Synthesis of Pyridyl Carbinols and Aldehydes In: Journal of the American Chemical Society 76, 1954, pp. 1286-1291, doi: 10.1021 / ja01634a026 .
↑ Jie Jack Li: Name Reactions , Springer, 2006, ISBN 978-3-642-01052-1 , pp. 54–56, doi: 10.1007 / 978-3-642-01053-8_131 .
↑ GR Newkome, KJ Theriot, VK Gupta, FR Fronczek, GR Baker: 124th mono-.alpha.-functionalization of 2,9-dimethyl-1,10-phenanthroline In: Journal of Organic Chemistry 54, 1989, p 1766-1769, doi: 10.1021 / jo00268a055 .
↑ C. Fontanes, E. Bejan, HA Haddou, GGA Belavoine: The Boekelheide Reaction: Trifluoroacetic Anhydride as a Convenient Acylating Agent In: Synthetic Communications 25, 1995, pp. 629-633, doi: 10.1080 / 00397919508011399 .

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[1] V. Boekelheide and WJ Linn: Rearrangements of N-Oxides. A Novel Synthesis of Pyridyl Carbinols and Aldehydes In: Journal of the American Chemical Society 76, 1954, pp. 1286-1291, doi: 10.1021 / ja01634a026 .

[2] Jie Jack Li: Name Reactions , Springer, 2006, ISBN 978-3-642-01052-1 , pp. 54–56, doi: 10.1007 / 978-3-642-01053-8_131 .

[3] GR Newkome, KJ Theriot, VK Gupta, FR Fronczek, GR Baker: 124th mono-.alpha.-functionalization of 2,9-dimethyl-1,10-phenanthroline In: Journal of Organic Chemistry 54, 1989, p 1766-1769, doi: 10.1021 / jo00268a055 .

[4] C. Fontanes, E. Bejan, HA Haddou, GGA Belavoine: The Boekelheide Reaction: Trifluoroacetic Anhydride as a Convenient Acylating Agent In: Synthetic Communications 25, 1995, pp. 629-633, doi: 10.1080 / 00397919508011399 .