Copper‐Catalyzed Decarboxylative CN Triple Bond Formation: Direct Synthesis of Benzonitriles from Phenylacetic Acids Under O₂ Atmosphere

Abstract

A copper-catalyzed reaction of phenylacetic acids with urea was found to afford benzonitriles under an oxygen atmosphere. This reaction proceeds smoothly by a sequence of decarboxylation, dioxygen activation, C À H bond functionalization, and nitrile formation with urea as the nitrogen source. Molecular oxygen was found to play a crucial role in this transformation. This reaction represents a novel protocol for the formation of benzonitriles in an environmental friendly way and with good functional group tolerability.Keywords: copper; decarboxylation; nitriles; oxygen; phenylacetic acids Transition metal-catalyzed decarboxylative couplings have attracted much attention in light of the readily accessible starting materials, simple operation and gaseous by-product (CO 2 as the only by-product). Among all of the decarboxylative coupling reactions, copper-catalyzed coupling reactions have lots of advantages over the prevailing palladium ones due to the ready availability, low price, less toxicity and ecofriendly properties of the metal; [1][2][3] yet copper-catalyzed decarboxylative coupling reactions [4,5] are relatively rare compared to the well-developed Pd-catalyzed decarboxylative coupling reactions. And transition metal-catalyzed decarboxylation at sp 3

Iron-Promoted Decarboxylation of Arylacetic Acids for the Synthesis of Aromatic Nitriles with Sodium Nitrite as the Nitrogen Source

“…The reaction was highly dependent on the solvent. Reactions in dimethyl sulfoxide (DMSO), N,Ndimethylformamide (DMF), or N-methyl-2-pyrrolidone (NMP) gave nitrile 2a in yields of 90, 59, and 76%, respectively (entries 11-13), whereas 1,4-dioxane, toluene, acetonitrile, and tetrahydrofuran (THF) were less effective as solvents (entries [14][15][16][17]. The reaction temperature also had a significant effect on the reaction, and a 90% yield was obtained when the reaction was performed at 50 °C (entry 11), whereas at 30 °C, the nitrile 2a was obtained in a lower yield of 52% (entry 18).…”

“…13 Song and co-workers reported a copper-catalyzed method in which the arylacetic acid undergoes decarboxylation to give an aromatic aldehyde that undergoes oxidative condensation with ammonia formed by decomposition of urea (Scheme 1a). 14 Kangani et al used sodium azide/Deoxo-Fluor as a reagent system to synthesize aromatic nitriles from arylacetic acids (Scheme 1b). 15 However, the use of extremely poisonous sodium azide and expensive Deoxo-Fluor restricts the application of this latter method.…”

Arylacetic Acids in Organic Synthesis

“…The Song group respectively investigated the synthesis of nitriles 17.1 from arylacetic acids (Eq. 17‐1) and their applications in the tandem construction of amides 17.5 (Eq. 17‐2).…”

“…17‐2). Under an oxygen atmosphere, both urea and ammonia in water were able to act as the source of NH 3 in these copper‐catalyzed decarboxylative C≡N bond formation (Scheme ).…”

Cellulose supported copper nanoparticles as a versatile and efficient catalyst for the protodecarboxylation and oxidative decarboxylation of aromatic acids under microwave heating

“…In some cases, the free carboxylic acids are required to be converted to esters or anhydrides for effective decarboxylation to take place [13]. Moreover, few examples of decarboxylation at sp 3 -carbon centre are reported [14][15][16]. Therefore, development of a recyclable metal catalytic system capable of carrying out decarboxylation at both sp 2 -and sp 3 -carbon centers under ligand and base free condition is essential.…”