摘要：Henry J. Hamann, Madison J. Snyder, Aman G. Singh, Abdulkhaliq A.Alawaed, and P. Veeraraghavan Ramachandran*

转自：康龙化成

Rapid, Room-Temperature Amidationvia Tandem Titanium Amido Complex and Titanium Carboxylate Intermediates

Henry J. Hamann, Madison J. Snyder, Aman G. Singh, Abdulkhaliq A. Alawaed, and P. Veeraraghavan Ramachandran*

Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States

—Org. Lett. 2025, doi: 10.1021/acs.orglett.5c03336

Recommended by Depei Meng_MC4

KEY WORDS:amidation(反应类型), C(sp2)─N (成键类型), acids, amines (原料), amides (产物),TiCl4Titanium amido complexes, titanium carboxylates (其他)

ABSTRACT: Titanium amido complexes are generated in situ from titanium tetrachloride. Subsequent reactions of these complexes with carboxylic acids generate activated titanium carboxylates which undergo amidation rapidly at room temperature. Spectroscopic studies and control reactions support the proposed mechanism and highlight the synthetic potential of this methodology.

Methods of amide bond formation utilizing metal amido reagents

Substrate Scope

Proposed reaction mechanism for the amidation of carboxylic acids via tandem titanium amido complex and titanium carboxylate formation, demonstrated for acetic acid and pyrrolidine starting materials

In conclusion, Henry J. Hamann et al. have reported a new metal amido amidation method. Titanium amido complexes are generated from the reaction of amines with TiCl4. These complexes react with a wide range of carboxylic acids to produce activated titanium carboxylates, which subsequently form amides following nucleophilic amine addition. The entire processoccurs nearly instantaneously at RT, providing amides from both aromatic and aliphatic carboxylic acids in yields greater than 70% for most examples.

Henry J. Hamann等人报道了一种新的使用金属酰胺化试剂进行酰胺化的策略。胺与TiCl4反应生成氨基钛络合物。这些配合物与多种羧酸反应生成活化的羧酸钛，被亲核的胺加成形成酰胺。整个过程在室温下几乎瞬间发生，同时多种芳香族和脂肪族羧酸都能以大于70%的收率反应给出对应的酰胺。反应后直接处理可得到产物，无需柱层析。

来源：新浪财经