Organic Chemistry

Section 6.11 Designing a Synthesis I: An Introduction to Multistep Synthesis 255

3-Hexyne can be obtained from the starting material by removing a proton from the sp

carbon, followed by alkylation. To obtain the desired product, a two-carbon alkyl

halide must be used in the alkylation reaction.

Designing a synthesis by working backward from product to reactant is not simply

a technique taught to organic chemistry students. It is used so frequently by experi-

enced synthetic chemists that it has been given a name—retrosynthetic analysis.

Chemists use open arrows to indicate they are working backward. Typically, the

reagents needed to carry out each step are not included until the reaction is written in

the forward direction. For example, the route to the synthesis of the previous ketone

can be arrived at by the following retrosynthetic analysis.

Once the complete sequence of reactions has been worked out by retrosynthetic analy-

sis, the synthetic scheme can be shown by reversing the steps and including the

reagents required for each step.

Example 2.Starting with ethyne, how could you make 1-bromopentane?

A primary alkyl halide can be prepared from a terminal alkene (using HBr in the

presence of a peroxide). A terminal alkene can be prepared from a terminal alkyne,

and a terminal alkyne can be prepared from ethyne and an alkyl halide with the

appropriate number of carbons.

Now we can write the synthetic scheme.

HC CH CH 3 CH 2 CH 2 CH 2 CH 2 Br

?

ethyne 1-bromopentane

CH 3 CH 2 CCH 2 CH 2 CH 3 CH 3 CH 2 C CCH 2 CH 3 CH 3 CH 2 CCH

retrosynthetic analysis

O

CH 3 CH 2 CCH CH 3 CH 2 C CCH 2 CH 3

1. NaNH 2
   2. CH 3 CH 2 Br
   1-butyne 3-hexyne

CH 3 CH 2 C CCH 2 CH 3 CH 3 CH 2 C CHCH 2 CH 3 CH 3 CH 2 CCH 2 CH 2 CH 3

OH O

H 2 O

H 2 SO 4

3-hexyne

Elias James Coreycoined the term

“retrosynthetic analysis.” He was

born in Massachusetts in 1928 and is

a professor of chemistry at Harvard

University. He received the Nobel

Prize in chemistry in 1990 for his

contribution to synthetic organic

chemistry.

CH 3 CH 2 CCH CH 3 CH 2 C CCH 2 CH 3

1. NaNH 2
   2. CH 3 CH 2 Br CH^3 CH^2 CCH^2 CH^2 CH^3

O

H 2 O

H 2 SO 4

synthesis

CH 3 CH 2 CH 2 CH 2 CH 2 Br CH 3 CH 2 CH 2 CH CH 2

retrosynthetic analysis

CH 3 CH 2 CH 2 CCH HC CH

1. NaNH 2
   2. CH 3 CH 2 CH 2 Br Lindlar
   catalyst

H 2 HBr

HC CH CH 3 CH 2 CH 2 CCHCH 3 CH 2 CH 2 CH peroxide

synthesis

CH 2 CH 3 CH 2 CH 2 CH 2 CH 2 Br

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