[109-00-2]  · C5H5NO  · 3-Hydroxypyridine  · (MW 95.11)

(acylation reactions; peptide synthesis)

Alternate Name: 3-pyridinol.

Physical Data: mp 126-129 °C; bp 151-153 °C/3 mmHg.

Form Supplied in: off-white solid; widely available commercially.

Analysis of Reagent Purity: mp; should be an off-white solid; if it becomes discolored it should be purified before use.

Purification: recrystallize from water or ethanol.

Handling, Storage, and Precautions: best stored in a stoppered vessel at 0 °C or below; avoid contact with strong acids and oxidizing agents; it is toxic and an irritant and so appropriate precautions should be taken.

Peptide Synthesis.

3-Hydroxypyridine has been coupled with amino acids using 1,3-Dicyclohexylcarbodiimide (DCC) to give an activated ester (1) which can be used in the formation of peptides1 as illustrated in eq 1. This can be useful if the purification of the peptide product proves to be a problem using other methods, since the intermediate (1) is soluble in dilute acid and hence easily removed from the reaction medium. In addition, the byproducts of the coupling reaction can easily be removed with aqueous acid.

Acylation Reactions.

3-Hydroxypyridine can be readily O-acylated using Acetyl Chloride and the product is of use as a selective acylating agent for alcohols and amines.2 For example, it will react with primary amines at rt to give good yields of the corresponding amides, whereas secondary amines react more slowly and diarylamines do not react at all (eq 2).

It is possible to increase the reactivity of 3-acetoxypyridine towards amines by the addition of Lewis acids such as Boron Trifluoride (eq 3), and this does allow some fine-tuning of the reactivity.

1. Taschner, E.; Rzeszotarska, B.; Lubiewska, L. AG(E) 1965, 4, 594.
2. Ueno, Y.; Takaya, T.; Imoto, E. BCJ 1964, 37, 864.

Barry Lygo

Salford University, UK

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