Methyl Nicotinate: uses and Synthesis method

Introduction

Methyl Nicotinate (MN), also known as methyl-3-pyridine carboxylate, methylpyridine -3-carboxylate and nicotinic acid methyl ester is an ester that is derived from nicotinic acid. Niacin – a water-soluble B vitamin –vitamin B3 - describes two related compounds, Nicotinic acid and nicotinamide. When applied on the skin, MN induces a local erythema and a transient increase in the skin perfusion through a vasodilatory response in the microcirculation. MN is chemically and biologically stable and easy to apply, making it a suitable drug for non-invasive temporary skin vasodilation. Its strong vasodilatory properties make MN interesting as a tool to evaluate microvascular reactivity[1].

Synthesis method

Presently, methyl nicotinate was synthesized by a simple esterification reaction, comprising reacting nicotinic acid with methanol in the presence of a sulphuric acid catalyst. The esterification reaction is usually a slow process and requires high temperature, high vacuum, and an esterification catalyst such as sulphuric acid, p-toluene sulfonic acid or toxic acid to affect the reaction rate[1]. Methyl nicotinate has been synthesized from nicotinic acid via a sulphuric acid-catalyzed esterification reaction. The reaction of nicotinic acid occurred in the presence of concentrated sulphuric acid solution under refluxing methanol for 13 hours to obtain methyl nicotinate, which underwent further purification by silica gel column chromatography in a solvent system of petroleum ether/ethyl acetate (4:1). Purity of the synthesized compound was ascertained by TLC. Analysis of the 1HNMR and Mass spectral data confirms the desired product. Methyl nicotinate (3-carboxymethylpyridine): White powder, yield 23.39%. m.p. = 40-42oC. IR (KBr cm-1 ): 1728.1(C=O), 1587.3(C=N-), 1429.2(C=C, aromatic), 1292.2-1120.6(C-O-C). 1HNMR (δH): 9.34 (s, H-2), 8.97 (br d, J = 8.0, H-4, H-6), 8.04 (br s, H-5), 4.05 (s, OCH3). EIMS (m/z): 137.0 [M + ], 122.0 [M-CH3] + , 106.0 [MOCH3] + .

Uses

Methyl nicotinate is an active ingredient in several medicinal products as a rubifacient and vasodilator for treating various diseases such as respiratory, vascular and rheumatoid disorders[3]. MN is a non-immunological compound, and it helps remove wrinkles, rejuvenates the skin, induces local skin vasodilation, and dilates the blood vessels for quicker, better absorption, and gives a warming sensation. Due to its rubefacient nature, it has been widely used in cosmetics as an ingredient in skin products like soaps, shampoo and creams. Aenictus species utilizes MN in its chemical communication system. MN is also an active flavour compound in fruits like Cupuacu (Theobroma grandiflora), Soursop (Annona muricata), Mammee apple (Mammea americana), Strawberries (Fragraria Vesca), Papaya, Guava, headspace of the living orchids Calanthe izu-insularis Ohwi et Satomi (Orcidaceae), Calanthe sieboldii Decne (Orcidaceae) and Tuberose and flowers like calanthe (Orchidaceae). In the 63rd meeting of the Joint FAO/WHO experts committee on food additives (JECFA), MN has been accepted as a flavouring agent and there is no safety concern for intake.

References

[1] Sherif Elawa. “Skin blood flow response to topically applied methyl nicotinate: Possible mechanisms.” Skin Research and Technology 26 1 (2019): 343–348.

[2] O. Erharuyi. “Synthesis and antinociceptive activity of methyl nicotinate.” Journal of Pharmacy & Bioresources 37 1 (2015): 54–59.

[3] B. Muralidhara Rao . “Identification and quantification of methyl nicotinate in rice (Oryza sativa L.) by gas chromatography–mass spectrometry.” Food Chemistry 105 2 (2007): Pages 736-741.

You may like