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.
CH
2
=CH
2
HBr(aq) CH
3
CH
2
-Br c NH3 CH
3
CH
2
NH
2
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…
C
4
H
9
Br + NaOH CH
3
-CH
2
-OH + NaBr
1-bromobutane butan-1-ol
M r
137 M r
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 RCH
2
NH
2
LiAlH4 in dry ether/hydrolyse with H
2
SO
4
Hydrolysis of the nitrile by refluxing with HCl (or NaOH followed by acid) produces the carboxylic acid
RCN +2H
2
O RCOOH +NH
3
Friedal – Crafts Alkylation reactions are another way of adding 1 or more C atoms
2.
Reducing the number of C’s
This is done by the Hofmann degradation in which an amide is heated with bromine and conc
KOH

O
R-C-NH
2
+ Br
2
+4KOH R*-NH
2
+ K
2
CO
3
+2KBr +2H
2
O * amine with 1 less C atom
Iodoform reaction
Iodine and sodium hydroxide can react with alcohols that have a CH
3
CH(OH) group and carbonyl compounds with a CH
3
C=O group to form CHI
3
and the salt of the carboxylic acid with one less carbon atom than the alcohol
RCH(OH)CH
3
I2 +NaOH RCOONa
ROCH
3
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