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Greener synthesis of medicinally relevant amides

Greener synthesis of medicinally relevant amides
Contributors
David Vosburg
Donald A. Strauss Professor of Chemistry | Harvey Mudd College
Learning Objets
Summary
This is an undergraduate organic laboratory experiment for the preparation of either of two medicinally relevant amide products from a biorenewable carboxylic acid and an amine using a green, non-sensitizing coupling reagent combination in acetonitrile. The procedure could also be adapted for different acids and amines, particularly when the amide products can be readily precipitated and filtered after addition of water to the reaction.

Oliver W. M. Baldwin, Linden H. Conrad-Marut, Gregory L. Beutner,* and David A. Vosburg* J. Chem. Educ. 2022, 99, 3747-3751.

https://pubs.acs.org/doi/10.1021/acs.jchemed.2c00760
Keywords
Organic chemistry laboratory
NMR
Peptides
Reaction Mechanisms

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Moderation state
Published
Object Type
Laboratory experiment
Journal articles
Audience
Introductory Undergraduate
Upper/Advanced Undergraduate
Published on
Green Chemistry Principles
Waste Prevention
Less Hazardous Chemical Syntheses
Safer Solvents and Auxiliaries
Design for Energy Efficiency
Use of Renewable Feedstocks
Safer Chemistry for Accident Prevention
U.N. Sustainable Development Goals (SDGs)
Good Health and Well-Being
Responsible Consumption and Production
Learning Goals/Student Objectives
Students will:
* perform an acylation reaction and isolate the product in good yield
* characterize the product (MS, IR, NMR)
* provide a mechanism for the reaction
* compare N-acyl imidazolium ions with N-acyl imidazoles as electrophiles
* compare the greenness of their procedure with a literature method
Common pedagogies covered
Collaborative/cooperative learning
Hands-on learning
Time required (if applicable)
one 3-hour laboratory period

Submitted by

David Vosburg
Safety Precautions, Hazards, and Risk Assessment
2-Furoic acid and N-Boc-piperazine can cause skin and respiratory irritation. 2-Furoic acid can cause eye damage. N-Boc-piperazine and 1-(2-pyrimidyl)piperazine can cause skin and eye irritation. N,N,N',N'-Tetramethylchloroformadinium hexafluorophosphate (TCFH) can cause skin, eye, and respiratory irritation. Acetonitrile is flammable and an eye irritant. N-Methylimidazole (NMI) can cause serious skin burns and eye damage. Acetonitrile and chloroform-d are toxic if swallowed, in contact with skin, or inhaled. N-Methylimidazole and chloroform-d are suspected of causing cancer as well as damage to fertility or organs. Gloves, lab coats, and protective eyewear should be worn for this experiment. A chemical fume hood is recommended for handling TCFH, NMI, acetonitrile, and chloroform-d.
Teacher Recommendations or Piloting Data (if available)
This experiment was successfully performed with undergraduates in a first—or second-semester organic laboratory course in Fall 2021, Spring 2022, Fall 2022, and Fall 2023. A virtual version of the experiment was also successfully implemented in Fall 2020.

Instructor notes are available in the supporting information here:
https://pubs.acs.org/doi/10.1021/acs.jchemed.2c00760?goto=supporting-info
Link to external
Facile Amide Bond Formation with TCFH–NMI in an Organic Laboratory Course Artic…