Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols and Hydroxide Catalyzed by a Ruthenium N-Heterocyclic Carbene Complex

Abstract

Primary alcohols have been reacted with hydroxide and the ruthenium complex [RuCl(IiPr)(p-cymene)] to afford carboxylic acids and dihydrogen. The dehydrogenative reaction is performed in toluene, which allows for a simple isolation of the products by precipitation and extraction. The transformation can be applied to a range of benzylic and saturated aliphatic alcohols containing halide and (thio)ether substituents, while olefins and ester groups are not compatible with the reaction conditions. Benzylic alcohols undergo faster conversion than other substrates, and a competing Cannizzaro reaction is most likely involved in this case. The kinetic isotope effect was determined to be 0.67 using 1-butanol as the substrate. A plausible catalytic cycle was characterized by DFT/B3LYP-D3 and involved coordination of the alcohol to the metal, β-hydride elimination, hydroxide attack on the coordinated aldehyde, and a second β-hydride elimination to furnish the carboxylate.

Silver‐Catalyzed Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols

“…We have previously established that the Cannizzaro reaction may be operating in these dehydrogenations of benzylic alcohols under basic conditions and this is also true for the silver‐catalyzed protocol. Subjecting benzaldehyde to the optimized conditions in entry 18 led to rapid formation of a mixture of potassium benzoate and benzyl alcohol where the latter was slowly converted into the former over a period of 4 h (Figure ).…”

“…Methyl p ‐(hydroxymethyl)benzoate furnished terephthalic acid monomethyl ester in 88 % yield with the parent terephthalic acid as the main byproduct (entry 7). The relatively little hydrolysis of the ester was surprising since we observed complete ester hydrolysis in our previous attempt to dehydrogenate the same substrate with a ruthenium catalyst . The reason is most likely the faster conversion of methyl p ‐(hydroxymethyl)benzoate with the silver‐catalyzed procedure leading to the insoluble potassium salt of terephthalic acid monomethyl ester.…”

“…Chemical shifts were measured relative to the signals of residual DMSO‐ d 5 ( δ H =2.50 ppm) and [D 6 ]DMSO ( δ C =39.5 ppm). The evolution of hydrogen gas was measured in the same way as described previously …”

“…p ‐(Methylthio)benzoic acid : Table , entry 11. Isolated as a white solid after recrystallization from water/ethanol in 65 % yield (435 mg).…”

“…The addition of the base also makes the overall transformation energetically more favored and prevents deactivation of the catalyst by the carboxylic acid. We have developed the ruthenium N‐heterocyclic carbene complex [RuCl 2 (I i Pr)( p ‐cymene)] for the synthesis of carboxylic acids and have also used the same complex for preparation of imines, amides and esters from primary alcohols…”