2-Methyl-3-nitrobenzyl alcohol

Chemical Properties

white to light yellow crystal powde

Uses

2-Methyl-3-nitrobenzyl alcohol was used to prepare 2-methyl-3-nitrobenzyl cyanide. It was also used in the synthesis of 20-membered macrocyclic thiodepsipeptide.

Synthesis Reference(s)

Journal of Medicinal Chemistry, 28, p. 1533, 1985 DOI: 10.1021/jm00148a028

Synthesis

General procedure for the synthesis of 2-methyl-3-nitrobenzenemethanol from 2-methyl-3-nitrobenzoic acid: 500 mL of tetrahydrofuran (THF) and 76.5 g of sodium borohydride (NaBH4) were mixed and stirred for 30 min at ambient temperature. Subsequently, a THF solution of 2-methyl-3-nitrobenzoic acid (250 g dissolved in 750 mL of THF) was added and stirring was continued for 0.5 h at ambient temperature. Next, 90 mL of methanesulfonic acid was slowly added to the reaction mixture with continuous stirring until the reaction was complete. Upon completion of the reaction, the organic layer was isolated by acidifying the reaction mixture by adding hydrochloric acid followed by extraction with ethyl acetate. The ethyl acetate was removed by evaporation to give 2-methyl-3-nitrobenzyl alcohol as a yellow oil. It was further treated with cyclohexane and crystallized to finally obtain purified 2-methyl-3-nitrobenzyl alcohol (Yield: 210 g, Yield: 84%).

References

[1] Journal of Medicinal Chemistry, 1985, vol. 28, # 10, p. 1533 - 1536
[2] Patent: WO2006/123356, 2006, A1. Location in patent: Page/Page column 21
[3] European Journal of Medicinal Chemistry, 1995, vol. 30, # 12, p. 973 - 982
[4] Helvetica Chimica Acta, 1948, vol. 31, p. 65,74
[5] Patent: WO2013/162072, 2013, A1. Location in patent: Page/Page column 938