Toluene-2-d1 synthesis

Yield:4409-84-1 80%

Reaction Conditions:

Stage #1: 2-methylphenyl bromidewith tert.-butyl lithium in diethyl ether at -78 - 0; for 4.16667 h;
Stage #2: with water-d2 in diethyl ether at 0 - 20;

Steps:

1) Synthesis of 2-deuteriobenzoic acid

In an oven-dried 100 mL round-bottomed flask, a solution of 2-bromotoluene (2.0 mL, 17 mmol, 1.0 eq.) and Et₂O (33 mL) were cooled to -78 °C. After 5 min, t-BuLi (1.3 M, 28.8 mL, 37.4 mmol, 2.2 eq.) was added via syringe over 40 min. The mixture was stirred for 2.5 h at -78 °C and then 1 h at 0 °C, before D₂O (1.5 g, 73.1 mmol, 4.3 eq.) was added via syringe. The mixture was then warmed to room temperature slowly overnight. The cloudy, white mixture was diluted with H₂O (20 mL). The layers were separated. The organic layer was washed with H₂O (20 mL x 3), dried (MgSO₄), filtered and concentrated under reduced pressure to give o-deuteriotoluene (1.2 g, 80%), wtihout further distilling. In a 100 mL round-bottomed flask equipped with a reflux condenser, o-deuteriotoluene (1.2 g, 13 mmol, 1.0 eq.), KMnO₄ (2.45 g, 32.2 mmol, 2.45 eq.), Na₂CO₃ (629 mg, 5.9 mmol, 0.452 eq.) and H₂O (43 mL, 0.3 M) were heated at reflux. After 8 h, the brown mixture was cooled to room temperature and filtered through a Celite pad, which was then washed with H₂O (10 mL). The filtrate was acidified using concentrated HCl. The product was then extracted with CH₂Cl₂ (20 mL x 3). The combined organic layers were washed with H₂O (20 mL) and concentrated to give a white powder, which was recrystallized from hot water to give deuteriobenzoic acid (133 mg, 11%) as white crystals. The ¹H NMR spectral data matched that of previously given in the literature. Deuterio benzamide was prepared according to the method of 2.2.

References:

Xu, Peng;Ding, Peng-Fei;Zhang, Mei-Qi;Xia, Yu-Shi;Xie, Ting [Tetrahedron Letters,2021,vol. 66,art. no. 152825] Location in patent:supporting information