PINNER Imino Ether Synthesis

This is an example of the Pinner imino ether synthesis (1). In the presence of an aqueous medium, the intermediate is hydrolyzed to the benzoic acid derivative. 

This is an example of the Pinner imido ether synthesis. The intermediate imido ester hydrogen chloride salt can be hydrolyzed to the ester or neutralized to the imino ester... 

The addition of dry HCI to a mixture of a nitrile and an alcohol in the absence of water leads to the hydrochloride salt of an imino ester (imino esters are also called imidates and imino ethers). This reaction is called the Pinner synthesis.103 The salt can be converted to the free imino ester by treatment with a weak base such as sodium bicarbonate, or it can be hydrolyzed with water and an acid catalyst to the corresponding carboxylic ester. If the latter is desired, water may be present from the beginning, in which case aqueous HCI can be used and the need for gaseous HCI is eliminated. Imino esters can also be prepared from nitriles with basic catalysts.104... 

The first stereoselective total synthesis of AI-77B, a gastroprotective substance, was accomplished by Y. Hamada and co-workers. In the final stages of the synthetic effort, the intramolecular Pinner reaction was utilized to convert the cyano group into the corresponding carboxylic acid. The nitrile substrate was dissolved in 5% HCI in methanol, and excess trimethyl orthoformate was added at 5 °C and the reaction mixture was stirred at this temperature for almost two days. Next, the cyclic imino ether hydrochloride salt was treated with water at room temperature followed by basic hydrolysis. Finally, the pH was adjusted with HCI to obtain the natural product. 

Adolf Pinner (Wronke, Posen, 31 August 1842-Berlin, 21 May 1909) was privatdocent (1871), associate professor (1878) in the University of Berlin, and professor in the Veterinary College, Berlin. He worked on imino-ethers R C( NH) OR, discovered pyrimidine, and proposed the correct formula for nicotine, confirmed by synthesis by A. Pictet. ... 

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