Environmentally Friendly Green O-Alkylation Reaction for Ethenzamide Synthesis

Ethenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this...

Full description

Saved in:
Bibliographic Details
Published in:Applied sciences 2025-01, Vol.15 (3), p.1342
Main Authors: Niedziejko-Ćwiertnia, Paulina, Drabczyk, Anna Karolina, Kułaga, Damian, Podobińska, Patrycja, Bachowski, Wojciech, Zeńczak-Tomera, Kamila, Michorczyk, Piotr, Sheng, Ruilong, Jaśkowska, Jolanta
Format: Article
Language:English
Subjects:
Acids
Analgesics
Aspirin
Chromatography
Efficiency
Ethanol
ethenzamide
Green chemistry
green synthesis
O-alkylation
phase transfer catalysts (PTC)
Potash
Potassium
Process planning
Product life cycle
Radiation
salicylamide
Sodium
solvent-free synthesis
Solvents
Temperature
Ultrasonic imaging
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ethenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this work, efficient and eco-friendly methods were developed for the synthesis of ethenzamide via the O-alkylation reaction of salicylamide. The reactions were carried out under conventional conditions in a solvent-free system using variant solvents and different phase transfer catalysts (PTC) in the presence of microwave radiation or ultrasonic conditions. It was shown that in solvent-free conditions using TBAB as a catalyst, ethenzamide can be obtained within 15 min at 80 °C with 79% yield. Meanwhile, using microwave radiation under the same conditions, the reaction time can be shortened to 90 s with 92% yield. Notably, high yields can be achieved under PTC in water (or organic solvent-free) conditions using microwave radiation (2 min, 94%) or ultrasound (10 min, 95% efficiency). The studies prove that the PTC synthesis process of ethenzamide can be conducted under mild conditions, with a shorter reaction time and remarkably lower energy consumption in comparison to conventional processes, thus actualizing “green chemistry” for practical ethenzamide preparation.
ISSN:2076-3417
2076-3417
DOI:10.3390/app15031342