4-Pentynoic acid

Chemical Properties

white to beige crystalline powder or flakes

Uses

4-Pentynoic acid was used:

• as building block for the synthesis of library of eight sequence-defined model oligomers
• in one-pot synthesis of the complex polycyclic heterocycles benzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazolinone derivatives
• in the synthesis of various allenenols lactones [5(E)-(2-allenylidene)-tetrahydro-2-furanones]
• in the synthesis of a cyctotoxic macrolide by ring-closing metathesis of a bis acetylene

Uses

4-Pentynoic Acid is a hypoglycemic agent shown to increase liver tyrosine aminotransferase and plasma corticosterone while decreasing blood sugar in rats.

General Description

4-Pentynoic acid undergoes copper-catalyzed intramolecular cyclizations to form enol lactones. It also reacts with 1-bromo-1-alkynes in the presence of a Pd catalyst to yield biologically active ynenol lactones.

Synthesis

General procedure for the synthesis of 4-pentynoic acid from 4-pentyn-1-ol: 4-pentyn-1-ol (1 mL, 10.7 mmol) was dissolved in acetone and the solution was cooled to 0 °C. Jones' reagent was slowly added dropwise under vigorous stirring until the reaction mixture remained orange in color. Subsequently, the reaction mixture was allowed to warm up to room temperature and Jones reagent was continued to be added dropwise to maintain the orange color. The reaction mixture was stirred at room temperature for 1 hour. Upon completion of the reaction, water was added and extracted several times with ether (Et2O). The organic phases were combined, washed with saturated brine and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed by concentration under reduced pressure to give the crude product. Purification by rapid chromatography on silica gel (eluent: hexane/ether=8:2) gave the colorless oily product 4-pentynoic acid in 82% yield.1H NMR (400MHz, CDCl3) δ: 2.61-2.59 (m, 2H), 2.52-2.48 (m, 2H), 1.98-1.95 (m, 1H) ppm.

References

[1] Organic Letters, 2016, vol. 18, # 11, p. 2600 - 2603
[2] Patent: WO2016/128541, 2016, A1. Location in patent: Page/Page column 53
[3] Patent: WO2017/162834, 2017, A1. Location in patent: Page/Page column 45
[4] Tetrahedron, 2009, vol. 65, # 24, p. 4664 - 4670
[5] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 2976 - 2979