4-Chloronicotinic acid

Chemical Properties

White to light brown solid

Uses

Building block used in a synthesis of benzocanthinones via tributyltin hydride radical induced cyclization. Also used in a synthesis of heterocyclic analogues of xanthone.

Uses

4-Chloronicotinic Acid is a building block used in a synthesis of benzocanthinones via tributyltin hydride radical induced cyclization. It is also used in a synthesis of heterocyclic analogues of xanthone.

Synthesis

1. Neutralization reaction: Neutralize 4-chloropyridine hydrochloride using 10% NaOH solution to obtain 4-chloropyridine (1). 2. lithiation reaction: 4-chloropyridine (1) (15 mmol) was dissolved in THF (250 ml) under nitrogen protection, cooled to -78 °C, and 1.2 equivalents of lithium diisopropylammonium was slowly added (1.5 M hexane solution containing 1 equivalent of THF, ALDRICH). 3. carboxylation reaction: the resulting anion is reacted with dry CO to produce 4-chloropyridine-3-carboxylic acid (3, i.e. 4-chloronicotinic acid). 4. Isolation and purification: The reaction mixture was treated and isolated to obtain 4-chloronicotinic acid as a colorless solid in 60-80% yield.

References

[1] Journal of Organic Chemistry, 1995, vol. 60, # 2, p. 292 - 296
[2] Patent: US2011/53975, 2011, A1. Location in patent: Page/Page column 60
[3] Patent: WO2009/87238, 2009, A2. Location in patent: Page/Page column 97; 98-99
[4] Patent: WO2005/21546, 2005, A1. Location in patent: Page/Page column 124-125
[5] Journal of Medicinal Chemistry, 2016, vol. 59, # 5, p. 1869 - 1879