N-(4-hydroxyphenyl)acetamide (commonly named paracetamol or acetaminophen) is a target molecule for many industries that produce chemicals for pharmaceutical applications. The industrial processes, however, use multistep procedures with low overall yield and/or severe drawbacks and problems in terms of sustainability. In the present paper, a one-pot synthesis is proposed based on the reductive carbonylation of nitrobenzene catalyzed by Pd(II)-complexes. Usually, such a reaction leads to a mixture of different products, including aniline, 4-aminophenol and 1,3-diphenylurea. However, the selectivity towards the possible products strongly depends by the ligands on the Pd(II)-catalyst, but also by the nature of the solvent. According to this, we have found that when the reaction was carried out in dilute acetic acid as a solvent, the [PdCl2(dppb)] catalyst precursor leads in one pot to N-(4-hydroxyphenyl)acetamide. Under optimized reaction conditions, it was possible to produce N-(4-hydroxyphenyl)acetamide with a 85 mol % of selectivity in ca. 5 h.

A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot

Andrea Vavasori
;
Lucio Ronchin
2023-01-01

Abstract

N-(4-hydroxyphenyl)acetamide (commonly named paracetamol or acetaminophen) is a target molecule for many industries that produce chemicals for pharmaceutical applications. The industrial processes, however, use multistep procedures with low overall yield and/or severe drawbacks and problems in terms of sustainability. In the present paper, a one-pot synthesis is proposed based on the reductive carbonylation of nitrobenzene catalyzed by Pd(II)-complexes. Usually, such a reaction leads to a mixture of different products, including aniline, 4-aminophenol and 1,3-diphenylurea. However, the selectivity towards the possible products strongly depends by the ligands on the Pd(II)-catalyst, but also by the nature of the solvent. According to this, we have found that when the reaction was carried out in dilute acetic acid as a solvent, the [PdCl2(dppb)] catalyst precursor leads in one pot to N-(4-hydroxyphenyl)acetamide. Under optimized reaction conditions, it was possible to produce N-(4-hydroxyphenyl)acetamide with a 85 mol % of selectivity in ca. 5 h.
2023
4
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10278/5044061
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