Efficient Synthesis of Mandel Acetates by Electrochemical Carboxylation of Benzal Diacetates

Abstract

Efficient synthesis of mandel acetate, 2‐acetoxy‐2‐phenylacetic acid, from benzaldehyde was successfully performed in two steps using electrochemical carboxylation of benzal diacetate as a key step. When benzal diacetate, readily prepared from benzaldehyde and acetic anhydride in one step, in DMF containing 0.1 M Bu4NBF4 was electrolyzed in the presence of carbon dioxide using an undivided cell equipped with a platinum plate cathode and a magnesium rod anode under constant current conditions, reductive cleavage of the C‐OAc bond followed by capture of carbon dioxide took place efficiently at the benzylic position to give mandel acetate in good to high yields. Wide scope, high yields and the use of carbon dioxide as a carbon source of the carboxyl group would provide novel environmentally‐benign synthesis of mandelic acid derivatives.

Recent advances in the electrochemically mediated chemical transformation of carbon dioxide

“…In 2019, Senboku and co-workers reported the first case of electrocarboxylation of benzyl diacetate to synthesize mandel acetate with a sacrificial anode under almost neutral and mild conditions (Scheme 13). 29 This reaction was carried out in a solution of DMF containing 0.1 M Bu 4 NBF 4 in a test-tube equipped with a platinum plate cathode and a magnesium rod anode at 0 °C with bubbling of CO 2 at a constant current of 25 mA cm −2 with 10 F mol −1 . Mandel acetate with electron-donating and electron-withdrawing groups on the benzene ring can be synthesized smoothly in good to excellent yields.…”

Electrochemical Fixation of Carbon Dioxide: Synthesis of Carboxylic Acids

“…After several attempts, we successfully performed efficient synthesis of mandel acetates from benzaldehydes in two steps using electrochemical carboxylation as a key step. Electrolysis of benzal diacetate (1,1‐diacetoxymethylbenzene) 80 a , readily prepared from benzaldehyde and acetic anhydride in one step, in DMF using an undivided cell equipped with a Pt cathode and an Mg anode in the presence of carbon dioxide resulted in reductive cleavage of one C−OAc bond followed by fixation of carbon dioxide at the benzylic position to give mandel acetate, 2‐acetoxy‐2‐phenylacetic acid ( 81 a ), in 85 % yield [43] . By tuning reaction conditions such as current density, electricity, solvent, and anode metal, wide substrate scope and high yield were accomplished and the results are summarized in Table 12.…”

Electrochemical Approaches to Carbonylative Coupling Reactions

“…In recent years, the rise of electrochemical carboxylation of benzene substrates with CO 2 as the C1 source is a breakthrough in the development of green chemistry. [59,60] The development of sacrificial anode-free has always been a challenge. Kim et al designed a system: useing tetramethylpiperidine-1-oxyl(TEMPO)-mediated anode replaced Mg and Al materials.…”

“…In recent years, the rise of electrochemical carboxylation of benzene substrates with CO 2 as the C1 source is a breakthrough in the development of green chemistry [59,60] . The development of sacrificial anode‐free has always been a challenge.…”