Pinner Reaction
The Pinner reaction is an acid-catalyzed reaction where a nitrile reacts with an alcohol to form an imino ester salt, also known as a Pinner salt[1][9]. This reaction was first described by Adolf Pinner in 1877[1]. The Pinner salt can undergo further nucleophilic additions to yield various products:
- With an excess of alcohol, it can form an orthoester.
- With ammonia or an amine, it can form an amidine. Di-nitriles may form imidines, such as succinimidine from succinonitrile.
- With water, it can form an ester.
- With hydrogen sulfide, it can form a thionoester[1].
The Pinner reaction is typically carried out under anhydrous conditions, and dry hydrogen chloride gas is often bubbled through the solution to avoid decomposition of the imino ester salt[9]. A wide range of nitriles can be used, including aliphatic, aromatic, and heteroaromatic substrates, although sterically hindered nitriles may be less reactive[9].
The reaction mechanism involves the treatment of the nitrile with gaseous HCl to afford the nitrilium ion, followed by the addition of the alcohol to deliver the imino ester salt. This intermediate can then react with various nucleophiles to produce different compounds[9].
The Pinner reaction can be carried out using either acid or base catalysis, with the choice depending on the electronic properties of the nitrile. Electron-poor nitriles, which are good electrophiles but poor nucleophiles, are typically more reactive under basic conditions, while electron-rich nitriles may react better under acidic conditions[1].
Lewis acid-promoted Pinner reactions offer a milder and chemoselective alternative for the synthesis of carboxylic esters from alcohols and nitriles[3][6]. This variant of the Pinner reaction can be advantageous due to the mild reaction conditions and the avoidance of toxic and difficult-to-handle gaseous hydrogen chloride.
In summary, the Pinner reaction is a versatile method for the synthesis of esters, orthoesters, amidines, and thionoesters from nitriles and alcohols, with the possibility of using either acid or base catalysis to optimize the reaction for different substrates.
Citations:
[1] https://en.wikipedia.org/wiki/Pinner_reaction
[2] https://www.youtube.com/watch?v=XkRoEWBam-E
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740506/
[4] https://www.organic-chemistry.org/namedreactions/pinner-reaction.shtm
[5] https://www.youtube.com/watch?v=wm4j9ddfhCA
[6] https://www.beilstein-journals.org/bjoc/articles/9/179
[7] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/pinner-reaction
[8] https://onlinelibrary.wiley.com/doi/10.1002/jhet.1990
[9] https://nrochemistry.com/pinner-reaction/
[10] https://www.sciencedirect.com/topics/chemistry/pinner-synthesis
[11] https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=RXNO%3A0000361
[12] https://www.youtube.com/watch?v=PGtuRfEb-iw