One crucial problems in organic synthesis concerns the synthesis of a specific disubstituted benzene — Organic Chemistry Chemistry Question
Organic synthesis involving regioselection
One crucial problems in organic synthesis concerns the synthesis of a specific disubstituted benzene through an electrophilic substitution reaction on a monosubstituted benzene. This problem is elegantly tackled in a synthesis of Tramadol, an analgesic drug (C16H25NO2), described below. The first step in this synthesis invovles:
[VISUAL]
A gives two equal intensity peaks at 172 and 174 in the highest m/z region of its mass spectrum. It gives a mixture of three isomeric mononitro derivatives on nitration under mild conditions.
Draw the structure for compound A. What is the regioselection observed in the reaction of phenol to form A? State the significance of this reaction.
Model Answer
The product obtained in the presence of catalyst HSbF6 is m-bromophenol. From the mass spectra given in the problem, direct bromination of phenol gives o/p–bromo derivatives as OH group present in phenol is o/p- directing.
[VISUAL] (Structure of compound A: m-bromophenol)
Consider the following reaction:
[VISUAL]
Mass spectrum of B shows equal intensity peaks at 186 and 188 in the highest m/z region.
Give structures of compounds B and C. How does the reactivity of B change on its conversion to C?
Model Answer
Compound B may undergo nucleophilic reaction at the carbon bearing bromine. Compound C contains a carbanion and hence functions as a nucleophile and will attack an electrophile. Thus, reactivity of B is reversed on its conversion to C (umpolung).
[VISUAL] (Structures of compound B and compound C in the solution)
Another intermediate compound D required for the synthesis of Tramadol is obtained as follows:
[VISUAL]
Show the structures of compound D and the final product Tramadol.
Model Answer
[VISUAL] (Structures of compound D and the final product Tramadol in the solution)
Give the structures of the possible stereoisomers of Tramadol.
Model Answer
Tramadol has two asymmetric carbon atoms. It has two pairs of enantiomers.
[VISUAL] (Structures of the four possible stereoisomers of Tramadol in the solution)