Phenacaine, also known as holocaine,[1] is a local anesthetic. It is approved for ophthalmic use.[2]
The synthesis of phenacaine begins with the condensation of p-phenetidine (1) with triethyl orthoacetate (2) to afford the imino ether (a Pinner salt, 3). Reaction of that intermediate with a second equivalent of the aniline results (4) in a net displacement of ethanol, probably by an addition-elimination scheme, producing the amidine, phenacaine (5).
In the patented synthesis,[3] phenacetin was used as precursor. Treatment with phosphorus trichloride (PCl3) gave the enol chloride, and reaction of this intermediate with p-phenetidine then completed the synthesis of phenacaine.