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 potassium cyanide (KCN) are reacted together via a Strecker reaction to give the corresponding cyanohydrin (3). The cyano group is then hydrated in acid to the corresponding amide, p-chloroatrolactamide (4). The amide group is then further hydrolyzed with a second equivalent of water in concentrated lye to give p-chloroatrolactic acid (5). Esterification then provides ethyl p-chloroatrolactate (6). Finally, nucleophilic addition with methylmagnesium iodide give phenaglycodol (7) crystals.^{[6] [7]}

In a second method, a mixed pinacol coupling reaction between para-chloroacetophenone and acetone that was catalyzed by magnesium activated with a small amount of trimethylsilyl chloride gave a 40% yield of phenglycodol.^[8]

See also

• Metaglycodol
• Fenpentadiol

Further reading

• Novel trifluoromethyl derivatives of substituted diols . US . 3134819 . Maxwell G, Pachter IJ . Smith Kline and French Laboratories Ltd . 26 May 1964 .
• Murphy HW . Pinacol Rearrangement of Phenaglycodol I. Characterization of Products Produced . Journal of Pharmaceutical Sciences . 53 . 298–301 . March 1964 . 14185017 . 10.1002/jps.2600530311 .

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. Mills J . 2-Chlorophenyl-3-methyl-2,3-butanediols . US . 2812363 . 5 November 1957 . .
7. GB. 788896. 1958-01-08. Improvements in or relating to novel substituted butanediol. Eli Lilly & Co.. Mills J .
8. 10.1016/j.tetlet.2004.03.109 . Mg-promoted mixed pinacol coupling . 2004 . Maekawa H, Yamamoto Y, Shimada H, Yonemura K, Nishiguchi I . Tetrahedron Letters . 45 . 20 . 3869–3872 .