Organic synthesis

The starting point for organic synthesis is to examine the required compound-target molecule! By looking at the functional groups it contains chemists can work backwards through a logical sequence of reactions until suitable starting materials can be found.

CH2=CH2 HBr(aq) CH3CH2-Br c NH3 CH3CH2NH2

Several steps may be required and a number of intermediates may have to be prepared and purified on the way to the target molecule.

Sometimes there may be more than one route to the target molecule. The preferred route is usually the one with the fewest steps, cost, time, disposal of waste materials, health and safety, most importantly the overall yield.

Working out yield

Organic reactions rarely give 100% yield due to by products that are also made…

C4H9Br + NaOH CH3-CH2-OH + NaBr

1-bromobutane butan-1-ol

Mr 137 Mr 74

If you start with 10.0g 1-bromobutane. If all the bromobutane became butan-1-ol we would get

74/137 x 10.0= 5.4g of the alcohol

If you did the expt and obtained 4.2g of alcohol you could work out the %yield

4.2/5.4x100=78%

Yields of 90% and above are excellent, 50% is adequate

Working out the yield of multistage synthesis

Eg 3 step synthesis, 90% yield at each step

A B C D

90% 90% 90%

Overall yield

90/100 x90/100x90/100=0.73

=73%

Getting the right isomer

The yield will be much lower if several isomers are formed when all you want is one product!

A real problem with substitution reactions involving benzene rings that already have a group substituted.

In this case they are all solids and can be separated by fractional crystallization or by chromatography.

This is difficult and time consuming.

Then you need to choose the reagent and the conditions required!

A few tricks to remember

  1. Increase the c chain length

You need to start with the halogenoalkane and reflux with KCN dissolved in ethanol. This will produce a nitrile*-nucleophilic substitution

R-X +KCN RCN* + KX

Reduction of the nitrile can produce a primary amine

RCN RCH2NH2 LiAlH4 in dry ether/hydrolyse with H2SO4

Hydrolysis of the nitrile by refluxing with HCl (or NaOH followed by acid) produces the carboxylic acid

RCN +2H2O RCOOH +NH3

Friedal – Crafts Alkylation reactions are another way of adding 1 or more C atoms

  1. Reducing the number of C’s

This is done by the Hofmann degradationin which an amide is heated with bromine and conc KOH

O

R-C-NH2 + Br2 +4KOH R*-NH2 + K2CO3 +2KBr +2H2O * amine with 1 less C atom

Iodoform reaction

Iodine and sodium hydroxide can react with alcohols that have a CH3CH(OH) group and carbonyl compounds with a CH3C=O group to form CHI3 and the salt of the carboxylic acid with one less carbon atom than the alcohol

RCH(OH)CH3 I2 +NaOH RCOONa

ROCH3 I2 +NaOH RCOONa

The carboxylic acid can be formed from the salt by adding acid.

  • Complete activity MD3.3 Classifying organic reactions
  • Complete Activity MD3.2 Making a toolkit of organic reactions- need to be learnt by heart. They will be used for devising multistage synthesis.
  • Problem 14.2
  • Complete activity MD3.3 Using the toolkit to synthesise medicines