Exp’t 421 A Short, OnePot Synthesis of （Exp 421年不短,OnePot合成的）.pdfVIP

Exp’t 421 A Short, One-Pot Synthesis of Bupropion (Wellbutrin, Zyban) Adapted by R. Minard from a procedure by Daniel M. Perrine,* Jason T. Ross, Stephen J. Nervi, and Richard H. Zimmerman, Department of Chemistry, Loyola College, Baltimore, MD, J. Chem. Ed., Nov. 2000, 1479-1481 Introduction: Bupropion, 3b, the hydrochloride salt of (±)-2-(t-butyl-amino)-3-chloropropiophenone, has a unique pharmacological profile. It was first marketed in 1985 by Burroughs-Wellcome (now Glaxo Wellcome) as an antidepressant, under the trade name Wellbutrin. Unlike selective serotonin reuptake inhibitors such as Prozac, Zoloft, or Paxil, it does not interfere with sexual performance, is less likely to cause drowsiness, and is as effective 1 as Ritalin in the management of attention-deficit hyperactivity disorder (ADHD) . But its most interesting feature was discovered by accident: in early clinical trials, many smokers taking the drug reported that after one or two weeks their craving for tobacco seemed to fade and they were able to quit smoking with few or no withdrawal symptoms (Johnston, J. A., Head of Psychiatry Clinical Development, Glaxo Wellcome; personal communication, 2 14 Dec 1998). When double-blind studies confirmed these anecdotal reports , bupropion was marketed in 1997 with a new name, Zyban, for use as an aid in smoking cessation. This experiment gives you the opportunity to synthesize a well-known pharmaceutical, and an “anti-addiction” drug. Perrine and coworkers investigated various approaches for the synthesis of Zyban. By modifying the published procedures3,4 , which require more than 24 hours and give