Preparation method of deuterated acetophenone_Kain Industrial Additive

Overview^[1]

Deuterated acetophenone is a deuterated reagent that can be prepared from benzene-d6 in two steps.

Preparation method^[1]

Step 1:

Preparation of acetophenone-2′,3′,4′,5′,6′-d5(2).

(Reference: Challacombe, K.; Leach, SE; Plackett, SJ; Meakins, GDJ Chem.Soc.Perkin Trans.1 1988,2213-2218.) In a 2L round-bottomed three-neck flask, a mechanical A stirrer, dropping funnel and reflux condenser connected to a gas absorption trap were used to treat the evolved hydrogen chloride. Benzene-d6(1) (100g, 1.19mol, 99.6atm%D) was placed in carbon disulfide (476mL). To this solution was added AlCl₃ (356g, 2.67mol) under nitrogen at room temperature. The mixture was heated in the oil bath until gentle reflux began and acetic anhydride (89.8 mL, 0.952 mol) was added via dropping funnel over 1 hour. The reaction mixture was stirred at the same temperature for 1 hour and then poured into concentrated HCl. Add glacial hydrochloric acid (400mL). Separate the organic layer. Extract the aqueous layer with diethyl ether (400mL*2). Wash the combined organic layers with water (400mL *2) and saturate. water-based. NaHCO₃ (400mL * 2) and brine (400mL), dried over MgSO₄ and concentrated in vacuo. The residue was purified by distillation under reduced pressure to give 2 (103 g, 87% based on acetic anhydride). Acetophenone-2′, 3′, 4′, 5′, 6′-d5 (2), yield 103g, 87%

Step 2:

Preparation of acetophenone-d8(3).

To a solution of acetophenone 2 (104 g, 0.829 mol) in 1,4-dioxane (99 mL) was added a solution of sodium hydroxide (one pellet) in deuterium oxide (248 mL). After stirring at room temperature for 24 hours, the mixture was extracted with diethyl ether (300 mL×3). The organic layer was dried with MgSO₄ and concentrated in vacuo to obtain crude product. The same operation is further repeated two more times. The final crude product was purified by distillation under reduced pressure to obtain 3 (90.1 g, 85%). Acetophenone-d8(3), yield 90.1g, 85%

Main reference materials

[1]Kobayashi Y , Hayashi N , Tan C H , et al. Toward the Creation of NMR Databases in Chiral Solvents for Assignments of Relative and Absolute Stereochemistry:? Proof of Concept[J]. Organic Letters , 2001, 3(14):2245-2248.