Delépine reaction

The Delépine reaction is an organic synthesis method used to produce primary amines. It was named after the French chemist Stéphane Marcel Delépine (1871–1965) who first described it in 1895[11]. The reaction involves the interaction of benzyl or alkyl halides with hexamethylenetetramine, followed by acid hydrolysis of the quaternary salts formed[2][11].

The reaction mechanism begins with the benzyl or alkyl halide reacting with hexamethylenetetramine to form a quaternary ammonium salt, with each reaction alkylating one nitrogen atom[2][5]. This salt is then converted to the primary amine by refluxing in a concentrated solution of ethanol and hydrochloric acid[2][5].

The Delépine reaction has several advantages, including selective access to the primary amine without side reactions[2]. However, it also has some downsides. The reaction is often performed using chloroform as a solvent, which is toxic, and it has poor atom economy, including the formation of several equivalents of formaldehyde (a known carcinogen) during the process[2].

The Delépine reaction has been applied in various contexts, such as the synthesis of 2-bromoallylamine from 2,3-dibromopropene[2], and the preparation of primary amines from activated alkyl halides[8]. It has also been used in microwave-induced reactions for the synthesis of certain benzodiazepinone derivatives[9].

Citations:

[1] https://academic-accelerator.com/encyclopedia/delepine-reaction

[2] https://en.wikipedia.org/wiki/Del%C3%A9pine_reaction

[3] https://pubs.acs.org/doi/10.1021/ja01169a518

[4] https://en.wikipedia.org/wiki/Sommelet_reaction

[5] https://www.sciencemadness.org/smwiki/index.php/Del%C3%A9pine_reaction

[6] https://pubmed.ncbi.nlm.nih.gov/18108978/

[7] https://www.lookchem.com/Chempedia/Basic-Chemical/Chemical-Reaction/8285.html

[8] https://pubs.acs.org/doi/abs/10.1021/acssuschemeng.0c05393

[9] https://www.tsijournals.com/abstract/application-of-microwave-induced-delepine-reaction-to-the-facile-one-pot-synthesis-of-7substituted-1-3dihydro2h1-4benzod-11710.html

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863291/

[11] https://www.chemistry-online.com/organic-chemistry/named-reactions/delepine-reaction/

[12] https://www.hakon-art.com/articles/application-of-microwave-induced-delepine-reaction-to-the-facile-one-pot-synthesis-of-7substituted-1-3dihydro2h1-4benzod.pdf

[13] https://en.wikipedia.org/wiki/Amine_alkylation

[14] https://synarchive.com/named-reactions/delepine-reaction

[15] https://pubs.acs.org/doi/pdf/10.1021/ja01169a518

[16] https://www.researchgate.net/publication/343647024_Assessing_the_Limits_of_Sustainability_for_the_Delepine_Reaction

[17] https://link.springer.com/chapter/10.1007/978-3-319-03979-4_83

[18] https://www.drugfuture.com/OrganicNameReactions/ONR96.htm

[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784050/