Phenacaine
Phenacaine, also known as holocaine, is a local anesthetic. It is approved for ophthalmic use.
Synthesis
The synthesis of phenacaine begins with the condensation of p-phenetidine with triethyl orthoacetate to afford the imino ether. Reaction of that intermediate with a second equivalent of the aniline results in a net displacement of ethanol, probably by an addition-elimination scheme, producing the amidine, phenacaine.In the patented synthesis, phenacetin was used as precursor. Treatment with phosphorus trichloride gave the enol chloride, and reaction of this intermediate with p-phenetidine then completed the synthesis of phenacaine.