Phenaglycodol

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]

Phenaglycodol
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • 2-(4-chlorophenyl)-3-methyl-2,3-butanediol
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.001.124
Chemical and physical data
FormulaC11H15ClO2
Molar mass214.69 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(C(C)(c1ccc(cc1)Cl)O)O
InChI
  • InChI=1S/C11H15ClO2/c1-10(2,13)11(3,14)8-4-6-9(12)7-5-8/h4-7,13-14H,1-3H3
  • Key:HTYIXCKSEQQCJO-UHFFFAOYSA-N

Synthesis
Patents:[6][7].

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.

40% one-step method:[8]

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 "Novel trifluoromethyl derivatives of substituted diols" U.S. Patent 3,134,819 also.
  • A Pinacol rearrangement occurs in acidic water:[9]

See also

References
  1. Usdin E, Efron DH, U.S. National Institute of Mental Health (1972). Psychotropic drugs and related compounds. National Institute of Mental Health; [for sale by the Supt. of Docs., U.S. Govt. Print. Off., Washington. ISBN 9780080255101.
  2. Vida J (19 July 2013). Anticonvulsants. Elsevier. pp. 578–. ISBN 978-0-323-14395-0.
  3. Haddad LM, Winchester JF (1983). Clinical Management of Poisoning and Drug Overdose. Saunders. ISBN 978-0-7216-4447-9.
  4. Drill VA (1958). Pharmacology in Medicine: A Collaborative Textbook. McGraw-Hill.
  5. Beckman H (1961). Pharmacology; the nature, action and use of drugs. Saunders.
  6. Jack Mills "2-chlorophenyl-3-methyl-2, 3-butanediols" U.S. Patent 2,812,363 (1957 to Eli Lilly Co.)
  7. Mills Jack, GB 788896 (1958 to Lilly Co Eli); CA, 52, 11926.
  8. Maekawa, Hirofumi; Yamamoto, Yoshimasa; Shimada, Hisashi; Yonemura, Kazuaki; Nishiguchi, Ikuzo (2004). "Mg-promoted mixed pinacol coupling". Tetrahedron Letters. 45 (20): 3869–3872. doi:10.1016/j.tetlet.2004.03.109.
  9. Murphy, Hubert W. (1964). "Pinacol Rearrangement of Phenaglycodol I". Journal of Pharmaceutical Sciences. 53 (3): 298–301. doi:10.1002/jps.2600530311.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.