Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 29. More About Multistep Organic Synthesis.
Editorial Comments
Urinary Graffiti? Excuse me?
As you can read in the Globe piece, "Urinary Graffiti" is the term used to describe marking behaviour of cats. The males are more territorial, of course, and they are more into this than the females. Being territorial intrinsically means being worried about loosing space. Reducing stress makes the cats also less worried about their space and urinary graffiti is reduced. Hence, marking cats commonly are given the anxiety-alleviating drug buspirone.
Buspirone is a somewhat complicated molecule and a molecular model is shown in the Visualization Center Accompanying Chapter 29.
Let's use this molecule for a "retrosynthetic analysis". With complicated molecules, it is best to approach the synthesis with a "devide and conquer" attitude. One needs to recognize smaller pieces of the molecule which are easily accessible and which can easily be connected. The following questions guide you through the retrosynthesis. Pertinent Text ReferencesQuestions
Question 1:
What kinds functional groups are present in buspirone?
Answer 1:
Carbonyl group, amide, imide, tertiary amine.
Question 2:
What methods do you know to prepare the functional groups that you have
identified? Suggest the most appropriate disconnections.
Answer 2:
All three tertiary amines are formed by way of reaction with a secondary
amine with halides.
Question 3:
Write down all the starting materials and outline a plan for the synthesis
of buspirone.
Answer 3:
The propanedioic acid that carries a spiro-connected five-membered ring at
the C2-carbon. Ammonia. 1-Bromo-4-chlorobutane. 2-Chloro-pyrimidine.
Tetrahydropyrazine.
Question 4:
Suggest a synthesis for the dioic acid used as starting material.
Answer 4:
Bis-alkylation of malonic acid with 1,4-dibromobutane.