Functional group interconversion — Synthesis & Retrosynthesis

Once the carbon skeleton is right, the rest of a synthesis is moving functional groups around. These steps are individually easy and collectively the place routes go wrong, because there are many of them and it is tempting to memorize them as a list rather than as a map.

The map has two axes, and almost every interconversion is a move along one of them.

Two kinds of move

Up or down the oxidation ladder — alkane, alcohol, aldehyde/ketone, carboxylic acid. These need an oxidizing or reducing agent, and they are the subject of the Oxidation & Reduction chapter.
Sideways, within one level — alcohol to alkyl halide, acid to ester to amide. These are substitutions, and they need no redox reagent at all.

Asking which kind of move a step is tells you immediately what class of reagent to reach for, and it catches the commonest planning error: trying to reach a carboxylic acid from an alcohol with a substitution, or trying to turn an ester into an amide with a reducing agent.

The moves worth knowing cold

The table, drawn as the map it is. Height is oxidation level and needs an oxidant or a reductant to change; width is everything else, and costs no redox reagent at all. Asking which direction a step moves tells you which shelf the reagent comes from before you have named it.The rows are worth reading for what shares a height. Ester, acid chloride, amide and acid are all one level, so interconverting them is substitution and never reduction — and an alkene, an alkyl halide and an alcohol are also one level, which is why the standard trick for moving an OH along a chain is to eliminate and add back, with no oxidation state changing anywhere in the two steps.

From	To	Reagent
Alkene	Alcohol (Markovnikov)	H₃O⁺, or oxymercuration
Alkene	Alcohol (anti-Markovnikov)	1. BH₃ 2. H₂O₂, HO⁻
Alkene	Alkane	H₂, Pd/C
Alkene	Diol (syn)	OsO₄ / NMO
Alkene	Two carbonyls	1. O₃ 2. Me₂S
Alcohol (1°/2°)	Alkyl halide	PBr₃, SOCl₂, or HX
Alcohol (1°)	Aldehyde	PCC, Swern or DMP
Alcohol (1°)	Carboxylic acid	Jones (aqueous CrO₃)
Alcohol (2°)	Ketone	Any of the above oxidants
Alcohol	Alkene	Conc. H₂SO₄, heat (E1)
Alkyl halide	Alkene	Strong bulky base (E2)
Alkyl halide	Nitrile	NaCN (S_N2)
Alkyl halide	Alkyne	Acetylide (S_N2)
Nitrile	Carboxylic acid	H₃O⁺, heat
Nitrile	1° Amine	LiAlH₄
Carboxylic acid	Ester	Alcohol, H⁺ (Fischer)
Carboxylic acid	Acyl chloride	SOCl₂
Acyl chloride	Ester or amide	Alcohol, or amine
Ester	1° Alcohol	LiAlH₄
Amide	Amine	LiAlH₄
Ketone/aldehyde	Alcohol	NaBH₄
Ketone/aldehyde	Alkane (CH₂)	Clemmensen or Wolff–Kishner
Ketone/aldehyde	Alkene	Wittig
Alkyne	cis Alkene	H₂, Lindlar
Alkyne	trans Alkene	Na, NH₃(l)

Read the table for the pairs rather than the rows. Several destinations can be reached with either of two reagents that give opposite outcomes — Markovnikov against anti-Markovnikov, cis against trans, aldehyde against carboxylic acid, syn diol against anti diol. Those pairs are where synthesis questions are built, because they are the choices only you can make.

Going around rather than through

Some conversions have no direct reagent and have to be done in two steps, and recognizing them saves a lot of time:

Alcohol to alkene at a specific position. Acid-catalyzed dehydration goes through a carbocation and gives the Zaitsev product, with rearrangement possible. To control where the alkene ends up, convert the alcohol to a halide first and eliminate with a base you choose.
Anti-Markovnikov alkyl halide from an alkene. There is no direct acid for it. Hydroborate to the anti-Markovnikov alcohol, then use PBr₃.
Aldehyde from an ester. Full reduction with LiAlH₄ overshoots to the alcohol, so either use DIBAL-H cold, or reduce all the way to the alcohol and oxidize back up with PCC. The second is two steps and uses only reagents from the table.
Moving a functional group along a chain. Eliminate to the alkene, then add back with the opposite regiochemistry. This is the standard way to shift an OH from one carbon to its neighbor, and it is almost always the intended answer when a target looks like the starting material with the group in the wrong place.

Worked example — the group is on the wrong carbon

Target: propan-1-ol, from propan-2-ol.

Same carbons, same oxidation level, same functional group — only the position differs, so no C–C chemistry and no redox is needed. The move is eliminate, then re-add the other way round.

1. Conc. H₂SO₄, heat → propene.
2. BH₃, then H₂O₂/HO⁻ → propan-1-ol, because hydroboration is anti-Markovnikov and puts the OH on the less substituted carbon.

Using acid-catalyzed hydration in step 2 would put the OH straight back where it started. The whole synthesis turns on choosing the anti-Markovnikov reagent, which is exactly the kind of pair the note above is about.

What carries forward

Nothing here is new chemistry — every row is a reaction from an earlier chapter, rearranged into a form you can search. What is new is the habit of asking, of any gap between two structures, whether it is a move along the ladder or a move across it, and whether the reagent you want exists or has to be reached in two steps.