N-Acetylation of Amines in Continuous-Flow with Acetonitrile-No Need for Hazardous and Toxic Carboxylic Acid Derivatives

György Orsy; Ferenc Fülöp; István M Mándity

doi:10.3390/molecules25081985

N-Acetylation of Amines in Continuous-Flow with Acetonitrile-No Need for Hazardous and Toxic Carboxylic Acid Derivatives

Molecules. 2020 Apr 23;25(8):1985. doi: 10.3390/molecules25081985.

Authors

György Orsy^{1

2}, Ferenc Fülöp^{1

3}, István M Mándity^{2

4}

Affiliations

¹ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
² MTA TTK Lendület Artificial Transporter Research Group, Institute of Materials and Environmental Chemistry, Research Center for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudosok krt. 2, 1117 Budapest, Hungary.
³ Research Group of Stereochemistry of the Hungarian Academy of Sciences, Dóm tér 8, H-6720 Szeged, Hungary.
⁴ Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Hőgyes Endre u. 7, H-1092 Budapest, Hungary.

Abstract

A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.

Keywords: acetonitrile; acetylation; flow chemistry; green chemistry; safe.

MeSH terms

Acetonitriles / chemistry*
Acetylation
Amines / chemistry*
Carboxylic Acids / chemistry*

Substances

Acetonitriles
Amines
Carboxylic Acids

Grants and funding

LP2017-8/2017/Magyar Tudományos Akadémia