Amidation of Aryl Chlorides Using a Microwave-Assisted, Copper-Catalyzed Concurrent Tandem Catalytic Methodology

Abstract

A concurrent tandem catalytic (CTC) methodology has been developed for the amidation of aryl chlorides where the aryl chloride is first converted to an aryl iodide via halogen exchange and the aryl iodide is subsequently transformed into the aryl amide. A variety of aryl chlorides were converted to aryl amides in up to 85% isolated yield using 20 mol % CuI, 60 mol % N,N′-cyclohexane-1,2-diamine, 2.2 equiv of K 2 CO 3 , and 1.05−1.5 equiv of amide in acetonitrile at 200 °C after 0.75−1 h. The same copper/ligand system served as multifunctional catalyst for both steps of the concurrent catalytic process with iodide present in substoichiometric amounts. Mechanistic studies were consistent with CTC amidation occurring via a nonradical mechanism. Kinetic modeling was conducted to investigate the effect of competitive direct amidation of an aryl chloride or aryl bromide on the formation of product over time during a CTC amidation reaction.

Crystal structures of N-[4-(trifluoromethyl)phenyl]benzamide and N-(4-methoxyphenyl)benzamide at 173 K: a study of the energetics of conformational changes due to crystal packing

“…In MOP, the energy required would only be around 7 kJ mol À1 (interactions #5 and #6). Although these energy values are internal energies and not enthalpies, they are reasonable values for heats of fusion and correlate with the melting points of the two crystal structures, 478 K for TFMP and 425 K for MOP (Chang et al, 2019). However, for TFMP, molecules should separate equally at the melting point on either side of a molecule.…”

“…In particular, aryl amides can be found in a variety of pharmaceutical drugs and in polymers such as Kevlar TM (Masse et al, 1998;Evano et al, 2004Evano et al, , 2008Satyanarayana et al, 2007;Tanner et al, 1989). A series of aryl amides were synthesized and isolated during the development of a copper-mediated concurrent tandem catalytic methodology for the amidation of aryl chlorides (Chang et al, 2019). The crystal structures of two of these aryl amides, derived from the cross-coupling of either 4-chlorobenzotrifluoride or 4-chloroanisole with benzamide, are reported here.…”

“…Details of the synthesis of the title compounds can be found in Chang et al (2019). Product crystals for both compounds were grown by slow diffusion of hexanes into a concentrated solution of the amide in ethyl acetate.…”

Modern Development in Copper‐ and Nickel‐Catalyzed Cross‐Coupling Reactions: Formation of Carbon‐Carbon and Carbon‐Heteroatom bonds under Microwave Irradiation Conditions

“…The presence of steric hindrance close to C−Cl bond of the substrates led to reduction in the outcomes and marginal yield was observed for the conversion of 1,4‐dichlorobenzene, Scheme 28. From mechanistic point of view, the aryl chloride undergoes in situ conversion to aryl iodide through halogen exchange and the iodide substrate is consequently transformed to the corresponding product [95] …”

Recent Advances in Microwave-Assisted Copper-Catalyzed Cross-Coupling Reactions

“…They have concluded the optimal conditions to be the use of catalytic amount of the dual catalysts, which is composed of copper(I) iodide (CuI) and [1,1 -Bis(di-tert-butylphosphino)ferrocene] dichloropalladium(II) (PdCl 2 (dtbpf)) in the presence of potassium carbonate (K 2 CO 3 ) as base in 1,4-dioxane as solvent, the resulting reaction mixture was then heated in a microwave oven at 120 • C for 30 min to produce the amide styrylation derivatives in moderate to excellent yields, Scheme 60. In a similar reaction, Chang, R.K. et al have reported the synthesis of aryl amides via a concurrent tandem catalytic methodology of converting aryl chloride to an aryl iodide using halogen exchange reaction under microwave irradiation [120]. The author systematically optimized the reaction by applying a catalytic amount (20 mol %) of copper(I) iodide (CuI) and N,N'-cyclohexane-1,2-diamine as ligand, in the presence of K 2 CO 3 as base in acetonitrile as solvent, the reaction mixture was then heated in a microwave oven at 200 • C for 45-60 min, affording the title compounds in moderate to very good yields, Scheme 61.…”