These common heterocyclic compound, 32673-41-9, name is 4-Imidazolemethanol hydrochloride, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Safety of 4-Imidazolemethanol hydrochloride
C. By hydrolysis of the esters obtained by the Friedel-Crafts reaction. 2-hydroxy-3-[(1H-imidazol-4-yl)methyl]-benzoic acid and 2-hydroxy-5-[(1H-imidazol-4-yl)methyl]-benzoic acid (hydrochloride). 181 g (1.35 mole) of 1H-imidazole-4-methanol hydrochloride are added in portions to a mixture of 156 ml (1.2 mole) of methyl 2-hydroxybenzoate and 675 g of polyphosphoric acid heated to 80 C. The reaction mixture is maintained with good stirring at this temperature for 288 hours. The mixture is then decomposed on ice, and extracted twice with toluene. The aqueous phase is alkalinized to pH 9.5 by the addition of 790 ml of a saturated aqueous solution of sodium hydroxide. The mineral salts which precipitate are removed by filtration and washed with methanol. The methanolic washing solution is added to the aqueous phase and the resulting mixture is concentrated with partial elimination of the methanol. The solution is then alkalinized to pH 10.3 by addition of a 10N aqueous solution of sodium hydroxide, and is heated at 100 C. for one hour and a half so as to saponify the esters. The aqueous solution is neutralized to pH 7.5 by addition of 10 N hydrochloric acid, filtered on Norit (activated carbon) and the filtrate is evaporated under reduced pressure. The residue is taken up three times in succession in a toluene-ethanol mixture and dried by azeotropic distillation. It is then partially dissolved in hot methanol and the insoluble mineral salts are removed by filtration. The filtrate is evaporated under reduced pressure, the residue is redissolved in a minimum of water, and purification is then carried out by passing through a column of Amberlite IR93 (height of the column: 60 cm; diameter: 8 cm; equivalence: 2.64 mole). Excess 1H-imidazole-4-methanol, together with its polymers, are eluted with water (the pH of the elude varies from 11.2 to 7.3). The elution is then continued with a 4% aqueous solution of hydrochloric acid. The acid elude (9 liters) is adjusted to pH 7.7 by addition of a saturated agueous solution of sodium hydroxide and is then evaporated under reduced pressure. The residue thus obtained is once again dried by azeotropic distillation with a toluene-ethanol mixture, and is then taken up in 1.6 liter of acetonitrile. It is then filtered. The residue on the filter (129 g) is chromatographed on silica (800 g, 15 mum) after having been previously deposited on 300 g of silica (0.2 to 0.5 mm) (eluent: 75:25 v/v ethyl acetate-ethanol). 5.99 g of 2-hydroxy-3-[(1H-imidazol-4-yl)methyl]-benzoic acid is thus obtained. M.P.: 245-252 C. (water). At the same time, 31 g of 2-hydroxy-5-[(1H-imidazol-4-yl)methyl]-benzoic acid are obtained.
The synthetic route of 4-Imidazolemethanol hydrochloride has been constantly updated, and we look forward to future research findings.
Reference:
Patent; U C B Societe Anonyme; US4923865; (1990); A;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem