A flexible Pinner preparation of orthoesters: the model case of trimethylorthobenzoate

摘要

In the absence of additional solvents, a novel procedure was implemented for the synthesis of trimethyl-orthoesters through the Pinner reaction. At 5 °C, the reaction of both aliphatic and aromatic nitriies (RCN; R = Et, Bu, Ph) with a moderate excess of MeOH and gaseous HCI gave the corresponding imidate hydrochlorides [RC(=NH)OR'HCI] in excellent yields (>90%). At 25-65 °C, the methanolysis of alkyl imidate salts provided trimethylortho-propionate and valerate, while only traces of trimethylorthobenzo-ate (TMOB) were observed. However, the aromatic hydrochloride could be readily converted into the hydrogenphosphate salt [PhC(=NH)OR'-H3PO4] 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.