Organic Chemistry

Section 18.12 Designing a Synthesis V: Disconnections, Synthons, and Synthetic Equivalents 767

When carrying out a disconnection, you must decide, after breaking the bond,
which fragment gets the positive charge and which gets the negative charge. In the ret-
rosynthetic analysis of cyclohexanol, we could have given the positive charge to the
hydrogen, and many acids (HCl, HBr, etc.) could have been used for the synthetic
equivalent for However, we would have been at a loss to find a synthetic equiva-
lent for an -hydroxycarbanion. Therefore, when we carry out the disconnection, we
assign the positive charge to the carbon and the negative charge to the hydrogen.
Cyclohexanol can also be disconnected by breaking the bond instead of the
bond, forming a carbocation and hydroxide ion.

The problem now becomes choosing a synthetic equivalent for the carbocation. A syn-
thetic equivalent for a positively charged synthon needs an electron-withdrawing
group at just the right place. Cyclohexyl bromide, with an electron-withdrawing
bromine, is a synthetic equivalent for the cyclohexyl carbocation. Cyclohexanol,
therefore, can be prepared by treating cyclohexyl bromide with hydroxide ion. This
method, however, is not as good as the first synthesis we proposed—reduction of
cyclohexanone—because some of the alkyl halide is converted into an alkene, so the
overall yield of the target compound is lower.

Retrosynthetic analysis shows that 1-methylcyclohexanol can be formed from the re-
action of cyclohexanone, the synthetic equivalent for the -hydroxycarbocation, and
methylmagnesium bromide, the synthetic equivalent for the methyl anion (Section 18.4).

Other disconnections of 1-methylcyclohexanol are possible because any bond to
carbon can serve as a disconnection site. For example, one of the ring bonds
could be broken. However, these are not useful disconnections, because the synthetic

C¬C

synthesis

O

1. CH 3 MgBr
   2. H 3 O+

HO CH 3

retrosynthetic analysis

HO CH 3 OH

−CH

+ 3

+

a

synthesis

Br OH

++HO−

retrosynthetic analysis

OH

+ HO−

+

C¬H

C¬O

a

H+.

synthesis

OH

1. NaBH 4


2. H+, H 2 O

O