Diethylthiambutene Explained

Diethylthiambutene (Thiambutene, Themalon, Diethibutin, N,N-Diethyl-1-methyl-3,3-di-2-thienylallylamine) is an opioid analgesic drug developed in the 1950s[1] which was mainly used as an anesthetic in veterinary medicine and continues, along with the other two thiambutenes dimethylthiambutene and ethylmethylthiambutene to be used for this purpose, particularly in Japan.[2] [3] It is now under international control under Schedule I of the UN Single Convention On Narcotic Drugs 1961, presumably due to high abuse potential, although little more information is available. It is listed under Schedule I of the US Controlled Substances Act as a Narcotic and has an ACSCN of 9616 with zero annual manufacturing quota as of 2013.

Synthesis

The conjugate addition of diethylamine [109-89-7] to ethyl crotonate [623-70-1] [10544-63-5] (1) gives ethyl 3-(diethylamino)butanoate, CID:10679145 (2). Addition of two equivalents of 2-thienyllithium to the ester gives the tertiary alcohol [94094-46-9] (4'). The dehydration of this then completes the synthesis of diethylthiambutene (5').

Notes and References

  1. Beckett AH, Casy AF, Harper NJ, Phillips PM . Analgesics and their antagonists: some steric and chemical considerations. II. The influence of the basic group on physico-chemical properties and the activity of methadone and thiambutene-type compounds . The Journal of Pharmacy and Pharmacology . 8 . 11 . 860–73 . November 1956 . 13368083 . 10.1111/j.2042-7158.1956.tb12216.x. 41750428 .
  2. Hayes MJ . The use of thiambutene hydrochloride . The Veterinary Record . 83 . 20 . 528 . November 1968 . 5694027 . 10.1136/vr.83.20.528-a . 45820838 .
  3. Harbison WD, Slocombe RF, Watts SJ, Stewart GA . Thiambutene and acepromazine as analgesic and preanaesthetic agents in horses and sheep . Australian Veterinary Journal . 50 . 12 . 543–6 . December 1974 . 4156466 . 10.1111/j.1751-0813.1974.tb14073.x .