Uses
Methyl 2,5-dihydroxybenzoate (methyl gentisate) may be used as a starting material in the synthesis of euonyminol.
Uses
methyl gentisate is also known as methyl dihydroxybenzoate. It is a skin-lightening ingredient that acts by inhibiting the melanocyte’s production of tyrosinase. It can be naturally obtained from gentian root.
Definition
ChEBI: Methyl 2,5-dihydroxybenzoate is a member of phenols and a benzoate ester.
General Description
Methyl 2,5-dihydroxybenzoate (methyl gentisate) is an alkyl ester of gentisic acid. It is reported to show less cytotoxic and mutagenic activity than hydroquinone with a potential to inhibit melanogenesis. It has been synthesized from 2,5-dihydroxybenzoic acid. The crystal structure of the molecule was found to be planar.
Synthesis
2,5-Dihydroxybenzoic acid (5.00 g, 32.5 mmol) was dissolved in methanol (33 mL) and concentrated sulfuric acid (5 mL) was added slowly and dropwise. The reaction mixture was heated under reflux conditions for 16 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was neutralized with saturated aqueous NaHCO3 to pH 7. Subsequently, the product was extracted with ethyl acetate (50 mL x 3), the organic layers were combined, washed with brine (20 mL), dried over anhydrous MgSO4, filtered and the filtrate was evaporated to give the light brown powdery product methyl 2,5-dihydroxybenzoate (5.13 g, 94% yield). The structure of the product was analyzed by 1H NMR (CDCl3) δ 10.35 (s,1H), 7.29 (d, J = 3.2 Hz, 1H), 7.02 (dd, J = 8.7,3.2 Hz, 1H), 6.89 (d, J = 8.7 Hz, 1H), 4.69 (s,1H), 3.95 (s,1H); 13C NMR (CDCl3) δ 170.1,155.8,147.6,124.0,118.5,114.7,112.1,52.4; HRMS (ESI):[M-H]- Calculated value of C8H7O4 167.0344, confirmed by measured value of 167.0359.
References
[1] Organic Letters, 2009, vol. 11, # 6, p. 1201 - 1204
[2] Journal of the American Chemical Society, 2010, vol. 132, # 16, p. 5869 - 5879
[3] Journal of Organic Chemistry, 2018, vol. 83, # 3, p. 1116 - 1133
[4] European Journal of Organic Chemistry, 2003, # 15, p. 2840 - 2844
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6321 - 6325
