Environmentally Benign Ritter Reaction Using Bismuth Salts as a Catalyst

Abstract

We developed an environmentally benign Ritter reaction of alcohols with nitriles using a commercially available bismuth salt as a less harmful catalyst. The detailed reaction profiles revealed that consumption of the ether by‐product as the reaction proceeded was the key for optimizing this reaction, and the yield of the target amide was improved by adding a small amount of water. This finding clearly reveals the significance of using a bismuth salt as the catalyst, as it is not deactivated in the presence of water. This catalyst system has a broad substrate scope, and even with 1 mol‐% of the catalyst, the reaction progresses smoothly. It is also possible to react stoichiometric amounts of nitriles and alcohols, thus reducing the amount of organic solvent required for the reaction. Furthermore, as the inexpensive bismuth catalyst can be easily removed using aqueous hydrochloric acid, a purification process that only required washing and drying without any organic solvents was successfully established.

Recent Applications of Ritter Reactions in Organic Syntheses

“…[36] In 2019, the classical Ritter reaction of nitrile 1 with alcohol 59 in the presence of a very small amount of BiBr 3 as catalyst produced the linear amides 60 in water (Scheme 22). [37] In 2019, Swarup et al introduced propylphosphonic anhydride (T3P®) as a catalyst in Ritter reaction of nitrile 1 and benzyl alcohols 59 to the synthesis of different bulky amides 61 (Scheme 23). [38] In 2016, acetamide 63 was synthesized via the classical Ritter reaction of acetonitrile 47 with (4,5-dichloroisothiazol-3yl) phenyl methanol 62 in HCOOH/H 2 SO 4 (Scheme 24).…”

“…In 2019, the classical Ritter reaction of nitrile 1 with alcohol 59 in the presence of a very small amount of BiBr 3 as catalyst produced the linear amides 60 in water (Scheme 22). [37] …”

Heavy Metals Make a Chain: A Catenated Bismuth Compound

“…Currently there is interesti nb ismuth and its compounds since they exhibit low toxicity and can be used as "environmentally friendlier" metal centredc atalysts for av ariety of reactions. [9,10] The reactions of bismuth halides with electron-richr eagents (coupling reagents) are often complicated but the metallic structurala lternative is ac ommon thermodynamic destination. The weak BiÀBi bond imparts sensitivity to catenatedb ismuth compounds, meaningt hat they often cannot survive the strong reducingc onditions needed to make them.F or the simplest of the bismuth-containing salts, BiÀBi bond formation achieves additional stabilization throughs ignificant crystal lattice energies.…”

Polyoxometalate–Ionic Liquid-Catalyzed Ritter Reaction for Efficient Synthesis of Amides

“…In addition, it also affected the formation of by-products (such as ethers, and alkenes). [11] Indeed, only a 50% yield of 1 was obtained when the reaction was performed in the absence of water (entry 5). With the amount of water increasing from 10 to 50 μL, the product yield increased from 64% to 82% correspondingly (entries 3, 6, and 7).…”

“…With the optimized reaction conditions in hand (Table 2, entry 3), the substrate scope of alcohols was first explored. As shown in Scheme 1, various 1-phenylethanol derivatives can be transformed into the corresponding Ritter products in up to 95% yields (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Among them, 1-phenylethanols with electron-withdrawing groups (2-8) generally gave better results than those with electron-donating groups (9)(10)(11).…”