Dipartimento di Scienze Molecolari e Nanosistemi dell’Universita Ca’ Foscari Venezia, Centre for Sustainable Technologies, calle Larga S. Marta, 2137-30123 Venezia, Italy
Green Chem., 2013,15, 2252-2260
Received 24 Apr 2013, Accepted 10 Jun 2013
The Pinner preparation of orthoesters was revisited achieving remarkable improvements. Outstandingly an unprecedented synthesis of trimethylorthobenzoate starting from benzonitrile has been described.
In the absence of additional solvents,
a novel procedure was implemented for the synthesis oftrimethylorthoesters through the Pinner reaction. At 5 °C, the reaction of both aliphatic and aromatic nitriles (RCN; R = Et, Bu, Ph) with a moderate excess of MeOH and gaseous HCl gave the corresponding imidate hydrochlorides [RC(
in excellent yields (>90%). At 25–65 °C, the methanolysis of alkyl imidate salts provided trimethylortho-propionate and valerate, while only traces of trimethylorthobenzoate (TMOB) were observed. However, the aromatic hydrochloride could be readily converted into the hydrogenphosphate salt [PhC(
] which, in turn, underwent a selective (>80%) reaction with MeOH to produce TMOB in a 62% isolated yield. This allowed for an unprecedented Pinner-type synthesis of TMOB starting from benzonitrile, rather than from the highly toxic trichloromethylbenzene. Overall, remarkable improvements in safety and process intensification were achieved.