1.1 Preparation of compound R-phenethylamine racemic lipoate
At room temperature, the racemic Thioctic (50.0 g, 0.24 mol) was dissolved in toluene, and R-phenethylamine (29.6 g, 0.24 mol) was slowly added dropwise to the system. After dropping, the mixture was stirred at room temperature for 1.5 hours, and filtered with suction , dried to obtain pale yellow solid R-phenethylamine racemic lipoate (74.0g, 93%).
1.2 Preparation of compound R-phenethylamine racemic Thioctic salt
At room temperature, the racemic Thioctic (50.0 g, 0.24 mol) was dissolved in ethyl acetate, and R-phenethylamine (29.6 g, 0.24 mol) was slowly added dropwise to the system. After dropping, the mixture was stirred at room temperature for 1.5 hours. Suction filtration and drying to obtain a pale yellow solid R-phenethylamine racemic Thioctic salt (71.6 g, 90%).
1.3 Preparation of compound R-phenethylamine racemic Thioctic salt
At room temperature, the racemic Thioctic (50.0 g, 0.24 mol) was dissolved in toluene, and R-phenethylamine (32.2 g, 0.26 mol) was slowly added dropwise to the system. After dropping, the mixture was stirred at room temperature for 1.5 hours, and filtered with suction , dried to obtain pale yellow solid R-phenethylamine racemic lipoate (77.9g, 98%).
2.1 Preparation of compound R-(+)-Thioctic
At room temperature, 5.0 g of R-phenethylamine racemic Thioctic salt was dissolved in 100 mL of acetone, and the temperature was raised to 40 ° C to dissolve. After the system was completely dissolved, 0.5 g of R-phenethylamine R-( +)-Lipoic acid salt was used as a seed crystal, the system was moved to 15°C and allowed to cool and crystallize naturally for 8 hours, suction filtered to obtain a light yellow solid, the obtained yellow solid was acidified with 10% dilute sulfuric acid, and 50 mL of acetic acid was added. Ethyl ester extraction, the organic layer was washed with water until weakly acidic, dried over anhydrous sodium sulfate, evaporated to dryness to obtain a crude yellow oil, which was recrystallized from n-hexane to obtain pure R-(+)-lipoic acid (1) (1.53 g, 46%), HPLC detection: R-(+)-lipoic acid (1): S-(-)-lipoic acid (2)=97:3. 1H NMRδ: 3.55～3.60 (m, 1H), 3.09～3.21 (m, 2H), 2.43～2.50 (m, 1H), 2.38 (t, J=7.4Hz, 2H), 1.88～1.95 (m, 1H), 1.63～1.76 (m, 4H), 1.42～1.57 (m , 2H); HR-ESI-MS m/z: Calcd for C8H14O2S2Na{[M+Na]+}229.0343, found 229.0346.
(1) take sodium sulfide in a beaker, add distilled water to the beaker, heat and stir to dissolve it below 50°C, and make a sodium sulfide solution of 3 mol/L; add sulfur to the gained sodium sulfide solution, stir to dissolve it, Make the concentration of sulfur in this sodium sulfide solution be 3.5mol/L, obtain mixed solution;
(2) Add 6,8-dichlorooctanoic acid ethyl ester and distilled water successively to the photoreactor to prepare a 3mol/L 6,8-dichlorooctanoic acid ethyl ester solution, then add a phase transfer catalyst to the solution, stir and heat up to 82-84℃;
(3) The mixed solution obtained in step (1) was added dropwise to the reaction solution of step (2) at a volume ratio of 5:3.5 within 180min, while a 1000W xenon lamp was used, and a 680nm cut-off filter was used to carry out the reaction solution. Photocatalysis, and stirring the reaction solution at a speed of 200r/min;
(4) Sodium sulfite is added to the photoreactor after the cyclization reaction, so that the concentration of sodium sulfite in the reaction solution is 0.45 mol/L, and the reaction is carried out under photocatalysis at 86-90° C. for 60 minutes.
(5) The reaction solution after the completion of the reaction is extracted at 80 to 90 ° C, the organic layer is diluted with toluene, and the aqueous layer is extracted with toluene at the same time, the toluene layers are combined, and the toluene layer is rotary evaporated to a constant weight to obtain ethyl lipoic acid. ester; and then hydrolyzed and acidified ethyl lipoate to obtain Thioctic.
