Rh^I‐Catalyzed Hydration of Organonitriles under Ambient Conditions

Abstract

Dedicated to Professor Ryoji Noyori on the occasion of his 70th birthdayThe hydration of organonitriles is a reaction of great synthetic significance for the preparation of organoamides (e.g., acrylamide and nicotinamide) in view of its broad industrial and pharmacological applications.[1] For example, hydration of acrylonitrile is used to produce more than 2 10 5 tons of acrylamide per year.[2] Classically the reaction proceeds in a sequence of distinct steps upon treatment with strong inorganic acid or base, but these methods are frequently unable to control overhydrolysis.[1f] Although several pioneering precedents involving molecular [3] and heterogeneous [4] catalysts have been reported, in many cases, drastic conditions including high temperatures (80-180 8C) or high pressure (e.g., 80 psi) are required. As an exception, Co III [3a,d] and Pt II [3e,o] complexes mediate hydration under milder conditions; however, the substrate range applicable under standard or ambient conditions remains unclarified. We report here a notable advance towards expanding the substrate scope, by demonstrating an easier to conduct and milder hydration of organonitriles using a low-valent Rh I -(OMe) species as the molecular catalyst (Scheme 1).The Rh I catalyst was prepared by treatment of commercially available [{Rh(OMe)(cod)} 2 ] (0.01 equiv) with PCy 3 (0.04 equiv) in anhydrous THF at 25 8C for 15 min under argon (cod = cyclooctadiene, Cy = cyclohexyl). After the solvent THF and residual cod had been removed by evaporation in vacuo, oxygen-free, Ar-saturated iPrOH was added. The iPrOH solution of the Rh I OMe/2 PCy 3 catalyst (Rh: 0.04 m) was treated sequentially with benzonitrile (1 a) (1 equiv) and H 2 O (5 equiv) at 25 8C under argon, and the reaction mixture was stirred at 25 8C for 17 h. Subsequent purification by column chromatography on silica gel provided benzamide (2 a) in 90 % yield. The reaction mixture was not contaminated by further hydration and/or alcoholysis products; in contrast, the formation of benzoic acid and/or the ester was frequently the side reaction in several methods previously described.[1f] Use of [{Rh(OH)(cod)} 2 ] in place of [{Rh(OMe)(cod)} 2 ] resulted in a slightly lower yield (74 %). Scant reactivity was observed with other Rh I complexes including [{RhCl(cod)} 2 ] and [Rh(acac)(cod)] (acac = acetylacetonate) under otherwise identical conditions, suggesting that the OR (R = H, Me) component is the critical functional group in facilitating the reaction. When we screened the solvents, we found that protic solvents (MeOH, EtOH, iPrOH, and tBuOH) led to rate enhancement (2 a, 60-99 %: 25 8C, 24 h), whereas aprotic solvents (dimethylacetamide (DMA), dimethyl sulfoxide, and N-methylpyrrolidinone (NMP)) resulted in low conversion (< 10 %). Additional experiments revealed that the yield of benzamide (2 a) depends least on the concentration of the Rh catalyst when the hydration is carried out in iPrOH, so that we chose this solvent for further screening. Two equivalents of PCy 3 per equivalent of Rh ...

Selective Ruthenium‐Catalyzed Hydration of Nitriles to Amides in Pure Aqueous Medium Under Neutral Conditions

“…/PCy 3 (cod = 1,5-cyclooctadiene, Cy = cyclohexyl), [11] all of them showing a remarkable activity. In contrast to these catalytic processes performed in organic solvents, and despite the growing interest to develop environmentally benign and safety processes, metal catalysts able to promote such a transformation in pure aqueous media are much scarcer (water is one of the best choices to replace organic solvents because of its low cost, availability, and nontoxic nature).…”

Nanoparticle‐Supported and Magnetically Recoverable Ruthenium Hydroxide Catalyst: Efficient Hydration of Nitriles to Amides in Aqueous Medium

“…[5] These methods suffer various drawbacks, especially the difficulty in separation of product and catalyst from the reaction mixture, as well as the use of inert atmosphere for handling air-sensitive metal catalysts. Heterogeneous systems have also been reported, such as alumina, [6] potassium fluoride doped Al 2 O 3 [7] and phosphates, [8] silica supported manganese oxides, [9] modified hydroxyapatite, [10] and ruthenium hydroxide coated on alumina and ferrites.…”

Benzoic Acid‐Catalyzed Transamidation Reactions of Carboxamides, Phthalimide, Ureas and Thioamide with Amines

“…[2] According to the authoritative statistics reports from the leading pharmaceutical companies, nearly 25% of the drug molecules contain an amide bond unit, [3] which demonstrates its importance in organic synthetic chemistry. [6] Consequently, many methods for the synthesis of amides have been reported, such as the reactions of amines with carboxylic acid derivatives, [7] esters, [8] aldehydes [9] or alcohols, [10] rearrangement of aldoximes, [11] hydration of nitriles, [12] aminocarbonylation processes, [13] hydroamination of alkynes. [6] Consequently, many methods for the synthesis of amides have been reported, such as the reactions of amines with carboxylic acid derivatives, [7] esters, [8] aldehydes [9] or alcohols, [10] rearrangement of aldoximes, [11] hydration of nitriles, [12] aminocarbonylation processes, [13] hydroamination of alkynes.…”