Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides

Abstract

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on a bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to generate a heterogeneous Cu 0 photocatalyst in situ, maintains high efficiency and selectivity upon scale-up, and operates by a radical mechanism with several beneficial features. This discovery will enable the engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.

Photochemical Synthesis of Acyl Fluorides Using Copper-Catalyzed Fluorocarbonylation of Alkyl Iodides

“…17−22 We recently reported that, under photochemical conditions, Cucatalyzed carbonylation of alkyl halides can proceed even with weak nucleophiles like K 2 CO 3 to form carboxylate derivatives. 23 Here, we report Cu-catalyzed, photochemical fluorocarbonylation of alkyl iodides using KF as the fluoride source (Figure 1c). 24 Benefits of this new method include short reaction times (4−6 h); the use of a commercially available, non-precious metal precatalyst with an inexpensive fluoride source; and chemoselective alkyl halide activation even in the presence of aryl halides.…”

“…24 Benefits of this new method include short reaction times (4−6 h); the use of a commercially available, non-precious metal precatalyst with an inexpensive fluoride source; and chemoselective alkyl halide activation even in the presence of aryl halides. We initially screened reaction conditions using the model substrate, 3-phenyl-1-iodopropane (1a), starting with standard carbonylation conditions inspired by our recent anhydrideforming reaction 23 (6 atm of CO, 3 equiv of KF, 10 mol % CuBr•SMe 2 , CH 3 CN). As expected, there was no formation of the desired acyl fluoride product (2a) under thermal conditions (Table 1, entry 1).…”

Response surface methodology based on the Box‐Behnken design for optimizing the synthesis of symmetrical anhydrides from acid chlorides using cerium (III) as a homogeneous catalyst

“…The importance of this family on an industrial scale has contributed to the development of several synthesis protocols, [10–11] the recovery of carboxylic acid anhydrides can be done through different access routes that we can cite for example the dehydration reactions of acids, the reaction of an acyl halide with a carboxy ion, [12] the use of strong coupling agents such as thionyl chloride, [13–15] phosgene, [16] phosphoranes [17] or isocyanate [18] . Although the yields are high, the above reactions require a strong source of energy or the use of reagents that are harmful and very dangerous to human health and the environment; hence the need to develop environmentally friendly processes.…”

“…Carboxylic anhydrides represent an important class of highly electrophilic reagents whose roles not only as acylating agents but also as key intermediates for the synthesis of many target molecules, particularly for the preparation of high added-value products, are of great interest for fundamental research involving drug, flavor and food industry. [1][2][3][4][5][6][7][8][9] The importance of this family on an industrial scale has contributed to the development of several synthesis protocols, [10][11] the recovery of carboxylic acid anhydrides can be done through different access routes that we can cite for example the dehydration reactions of acids, the reaction of an acyl halide with a carboxy ion, [12] the use of strong coupling agents such as thionyl chloride, [13][14][15] phosgene, [16] phosphoranes [17] or isocyanate. [18] Although the yields are high, the above reactions require a strong source of energy or the use of reagents that are harmful and very dangerous to human health and the environment; hence the need to develop environmentally friendly processes.…”

Cd-Doped Biphase In2O3 Nanospheres with High Sensitivity and Selectivity for Acetic Anhydride Sensors

“…The Occupational Safety and Health Administration (OSHA) believes the exposure limit should be less than 5 ppm . Not only that, it is also the raw material for the production of methamphetamine, heroin, and other drugs. − Low detection limits, low detection temperatures, and high selectivity for acetic anhydride are necessary for medical, industrial, and drug detection considerations.…”