C-C bond formation

Problem # 723

Show how to prepare each compound from vinyl benzene.

How would you prepare the methyl ester of each compound?

Vinyl benzene is a common starting material and intermediate in second semester organic chemistry synthesis problems, so you should be familiar how to make vinyl benzene from benzene (see problem 722).

The trick to many synthesis problem is to realize how many carbons need to be added, as that will determine which route you use.

a) Adding zero carbons: alcohol then oxidation

All you need is an alcohol added to the last carbon, which you can oxidize to a carboxylic acid. So from the alkene do an anti-Markovnikov addition of H₂O via hydroboration, followed by oxidation using Jones reagent (aqueous chromium, Cr⁶⁺ in acid).

b) Adding one carbon: nitrile (cyanide, CN)

When you add one carbon that screams "cyanide!" The most common way to add CN is using NaCN with an alkyl halide in an S_N2 reaction.

Because you want to add the extra carbon (CN) to the end of the chain, you want to do an anti-Markovnikov addition using HBr and perioxides. Then add NaCN to form the nitrile.

To convert a nitrile to a carboxylic acid, hydrolyze under acidic conditions (add water with acid, H₃O⁺).

c) Adding two carbons: epoxide

When you need to add two carbons, ethylene oxide is the way to go. But ethylene oxide is an electrophile, so first you must transform vinyl benzene into a nucleophile, specifically, a Grignard reagent.

We want the Grignard part (MgBr) on the end, so do an anti-Markovnikov addition with HBr/peroxides followed by Mg⁰/ether. Then add the epoxide which adds two carbons with an alcohol on the end. Finally, oxidize using Jones reagent.

Each carboxylic acid can be converted to its methyl ester via Fischer esterification: add methanol under acidic conditions (CH₃OH/H⁺).

Problem Details

MendelSet practice problem # 723 submitted by Matt on July 24, 2011.

Subject: Organic Chemistry

Subject Topic(s): Carboxylic Acids (Inductive Effects, Esterification)

Question Type: Synthesis (show how to prepare X from Y..)

Keyword(s): epoxides, oxidation, carboxylic acids, C-C bond formation

Problem # 722

Show how to prepare vinyl benzene from benzene.

Solution

This is a good synthesis to know, because vinyl benzene is a good starting point for many synthesis problems you will encounter down the road.

An ethyl group can be added to benzene via Friedel-Crafts alkylation.

To add that alkene, we you will have to do some sort of elimination reaction. The easiest way to do this is via bromination. Free radical bromination (with NBS or Br₂/hν) will add a bromine to the position of the most stable radical, which is the benzylic position (due to resonance).

Then adding a strong base like potassium tert-butoxide will do an E2 reaction to form the alkene.