3-Acetylpyridine

Chemical properties

clear colorless to yellow liquid

Chemical properties

A colorless liquid with sweet, nutty, popcorn-like aroma

Occurrence

Reported found in roasted filberts, beer, brandy, coffee, malt and wheaten bread.

The Uses of 3-Acetylpyridine

3-Acetylpyridine used as an intermediate for the synthesis of risedronate sodium, inhibitor of bone resorption. It is also used in perfumery.

The Uses of 3-Acetylpyridine

Used in the fragrance industry and as an intermediate in the synthesis of a number of clinical drugs, including Imatinib, Mesylate, Metyrapone, Telithromycin, and Ridogrel. An analog of nicotinamide that competes for incorporation into NAD. It has been used to chemically lesion the inferior olive nucleus, thereby eliminating climbing fibers within the cerebellar cortex.

Definition

It is a nicotinic acidantagonist.

Preparation

Dry distillation of calcium nicotinate with calcium acetate.

Production Methods

Produced from Ethyl nicotinate and Ethyl acetoacetate, in principle by hydrolysis of Aceto acetylpyridine.

Safety Profile

Poison by ingestion. Moderately toxic by intraperitoneal routeMutation data reported. A flammable liquid. When heated to decomposition emits toxic fumes of NOx,. See also KETONES

Intermediate

3-Acetylpyridine is a vital chemical intermediate with broad applications across various industries including agriculture and pharma. It plays a vital role in the synthesis of key agro compounds such as 2,3-Dichloropyridine, Chlorantraniliprole, Cyantraniliprole and beyond.  

Purification Methods

It is purified by dissolving in HCl, extracting with Et2O to remove the possible impurity of nicotinic acid, basified with NaOH and extracted with Et2O. The dried extract is filtered, evaporated and the residual oil is distilled. If the NMR spectrum indicates further impurities, then convert it to the phenylhydrazone (m 137o, yellow needles from EtOH). This is hydrolysed with HCl [Engler & Kiby Chem Ber 22 597 1889], the phenylhydrazine HCl is removed by filtration, NaNO2 is added, the solution is basified with aqueous NaOH and extracted with Et2O as before and distilled at atmospheric pressure to give 3-acetylpyridine as a colourless oil. Purification can also be achieved by shaking with 50% aqueous KOH, extracting with Et2O, drying the extract and distilling it at atmospheric pressure or in vacuo. [Kloetzel & Chubb J Am Chem Soc 79 4226 1957.] The hydrochloride has m 180-181o (from MeOH/EtOH), the picrate has m 133.8-134.8o (from H2O), and the phenylhydrazone has m 137o (129-130o)(needles, from EtOH) [Webb & Webb J Am Chem Soc 71 2285 1949]. The ketoxime has m 112o (from EtOH or *C6H6). [Strong & McElvain J Am Chem Soc 55 816 1933, Kolloff & Hunter J Am Chem Soc 63 490 1941, Beilstein 21/7 V 394.]