A continuous flow protocol for the preparation of the tricyclic antidepressant (TCA) amitriptyline is reported. The advantages of flow chemistry when handling organometallic agents as well as when performing reaction with gases are demonstrated. Continuous multilithiation combined with carboxylation and the Parham cyclization, a Grignard addition and thermolytic water elimination by inductive heating are key features of the multistep protocol.
The oxorhenium(V) chelates [ReOCl(N,O‐L)(PPh3)] [N,O‐L=(OCH2CH2)N(CH2CH2OH)(CH2COO) ( 2 ), (OCH2CH2)N(CH2COO)(CH2COOCH3) ( 3 )] and [ReOCl2(N,O‐L)(PPh3)] [N,O‐L=C5H4N(COO‐2) ( 4 ) C5H3N(COOCH3‐2)(COO‐6) ( 5 )] have been prepared by reaction of [ReOCl3(PPh3)2] ( 1 ), in refluxing methanol, with N,N‐bis(2‐hydroxyethyl)glycine [bicine; N(CH2CH2OH)2(CH2COOH)], N‐(2‐hydroxyethyl)iminodiacetic acid [N(CH2CH2OH)(CH2COOH)2], picolinic acid [NC5H4(COOH‐2)] or 2,6‐pyridinedicarboxylic acid [NC5H3(COOH‐2,6)2], respectively, with ligand esterification in the cases of 3 and 5 . All these complexes have been characterized by IR and multinuclear NMR spectroscopy, FAB+‐MS, elemental and X‐ray diffraction structural analyses. They act as catalysts, in a single‐pot process, for the carboxylation of ethane by CO, in the presence of potassium peroxodisulfate K2S2O8, in trifluoroacetic acid (TFA), to give propionic and acetic acids, in a remarkable yield (up to ca. 30%) and under relatively mild conditions, with some advantages over the industrial processes. The picolinate complex 4 provides the most active catalyst and the carboxylation also occurs, although much less efficiently, by the TFA solvent in the absence of CO. The selectivity can be controlled by the ethane and CO pressures, propionic acid being the dominant product for pressures about ca. 7 and 4 atm, respectively (catalyst 4 ), whereas lower pressures lead mainly to acetic acid in lower yields. These reactions constitute an unprecedented use of Re complexes as catalysts in alkane functionalization. 相似文献
Radical acylations to prepare carbonyl compounds are described and focus on indirect acylation approaches using sulfonyl oxime ethers under tin‐mediated and tin‐free conditions. The efficiency of carboxylic acid derivatives as carbonyl group radical acceptors in radical acylation and carboxylation reactions is discussed. 相似文献