Phenaglycodol Explained

Phenaglycodol (brand names Acalmid, Acalo, Alterton, Atadiol, Felixyn, Neotran, Pausital, Remin, Sedapsin, Sinforil, Stesil, Ultran)[1] is a drug described as a tranquilizer or sedative which has anxiolytic and anticonvulsant properties.[2] [3] It is related pharmacologically to meprobamate, though it is not a carbamate.[4] [5]

Synthesis

p-Chloroacetophenone and NaCN are reacted together to give the corresponding cyanohydrin (cf Strecker synthesis), CID:12439573. The cyano group is then hydrated in acid to the corresponding amide, p-chloroatrolactamide, CID:15255544 (4). The amide group is then further hydrolyzed with a 2nd equivalent of water in concentrated lye to p-chloroatrolactic acid, [4445-13-0] (5). Esterification to Ethyl p-chloroatrolactate [100126-96-3](6). Finally, nucleophilic addition a couple of equivalents of MeMgI are added to the ester give Phenaglycodol (7) crystals.

A mixed Pinacol coupling rxn between 4-chloroacetophenone [99-91-2] and acetone with magnesium activated with a small amount of trimethylsilyl chloride gave a 40% yield of phenglycodol.

Notes

See also

Notes and References

  1. Book: Usdin E, Efron DH, ((U.S. National Institute of Mental Health)) . Psychotropic drugs and related compounds. 1972. National Institute of Mental Health; [for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington. 9780080255101.
  2. Book: Vida J . Anticonvulsants. 19 July 2013. Elsevier. 978-0-323-14395-0. 578–.
  3. Book: Haddad LM, Winchester JF . Clinical Management of Poisoning and Drug Overdose. registration. 1983. Saunders. 978-0-7216-4447-9.
  4. Book: Drill VA . Pharmacology in Medicine: A Collaborative Textbook. 1958. McGraw-Hill.
  5. Book: Beckman H . Pharmacology; the nature, action and use of drugs. 1961. Saunders.
  6. Murphy, Hubert W. (1964). "Pinacol Rearrangement of Phenaglycodol I". Journal of Pharmaceutical Sciences. 53 (3): 298–301. doi:10.1002/jps.2600530311.