Intermolecular and Intramolecular Friedel‐Crafts Acylation of Carboxylic Acids using Binary Ionic Liquids: An Experimental and Computational Study

Abstract

Traditional Friedel‐Crafts acylation with acid halides suffers from waste byproducts such as SO2, HCl, and the hydrolysis of Lewis acid catalyst. Thus, the environmentally benign intermolecular and intramolecular Friedel‐Crafts acylation of arenes with carboxylic acids as acylating agents has been investigated using a mixture of deep eutectic solvent and an ionic liquid as reaction media under microwave irradiation. The Friedel‐Crafts acylations with carboxylic acids as acylating agents are challenging due to the low reactivity of carboxylic acids. In this paper, the desired products were obtained at moderate to good yields under microwave irradiation for a short reaction time. The Friedel‐Crafts cyclization of 4‐phenylbutyric acid is more effective than 3‐phenylpropionoic acid under the present method. The reaction mechanism is proposed by combining experiments with density functional theory calculations, highlighting the critical role of ZnCl2, triflate anion (CF3COO−) in binary ionic liquids, and acidic conditions in accomodating a kinetic accessible pathway making the C−C bond.

Mechanism of Friedel–Crafts Acylation Using Metal Triflate in Deep Eutectic Solvents: An Experimental and Computational Study

“…In the second part, the Friedel–Craft reaction catalyzed by DES can occur following the reported mechanism . Complex IV undergoes another ligand-exchange process with one more equivalent of triflate to regenerate the catalyst.…”

“…In the second part, the Friedel–Craft reaction catalyzed by DES can occur following the reported mechanism. 45 Complex IV undergoes another ligand-exchange process with one more equivalent of triflate to regenerate the catalyst. Due to the exchange ligand steps being mainly contributed by dynamic behavior, 62 the kinetics of the reaction is not determined.…”

“…Metal triflates, water-compatible Lewis acids, have increased interest in organic synthesis. − Metal triflates are considered green catalysts for alternative traditional Lewis acids due to their strong Lewis acidity and high tolerance toward water. − Metal triflates can be used with organic solvents or water, and they are easily recycled without a decrease in catalytic activity. − Metal triflate has been known as an effective catalyst for Friedel–Craft transformation in the past 2 decades. ,− While there is the conventional understanding that Lewis acid is a stoichiometric requirement for the reaction and metal cation can fill this role, triflate anion also is crucial. − Currently, our theory study highlights that triflate helps stabilize the acylium and accommodate kinetic accessible pathways in the C–C bond formation process . However, the details of how this species is formed under the support of Lewis acid are still unexplored, especially when extending the list to rare-earth metals.…”

“… 42 − 44 Currently, our theory study highlights that triflate helps stabilize the acylium and accommodate kinetic accessible pathways in the C–C bond formation process. 45 However, the details of how this species is formed under the support of Lewis acid are still unexplored, especially when extending the list to rare-earth metals. To get more insights into the chemical transformation, a density functional theory (DFT) calculation also is performed.…”

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

“…Successive research for the Friedel-Crafts acylation lead to the development of various reaction protocols using different metal salts [25][26][27][28][29][30] and ionic liquids [31][32][33][34][35] to acylate [36][37][38][39][40][41], alkylate [42][43][44], benzylate [45][46][47] and alkenylate [48,49] different benzene derivatives. But surprisingly, a robust protocol using commercially available and cost-efficient metal salts in a water and air stable ionic liquid is still hard to find [50,51].…”