BASIC CONCEPT OF ORGANIC SYNTHESIS

Organic Chemistry is divided into 2 broad branches:

• Natural Product Organic Chemistry

• Synthetic Organic Chemistry

Natural Product Chemistry deals with naturally occurring

organic compound, a branch of Chemistry that deals with and
focuses on different parts of nature, e.g plants, animals,
organisms. The driving force of the natural product organic
chemistry is in the production of drugs.
Synthetic Organic Chemistry is the breakdown of organic
compounds. Organic synthesis can be likened to formation and
arrangement of building blocks in a house.
The synthetic organic chemistry is studied to:
(i) Confirm the structure of a new natural product.
(ii) Help to produce product in an industrial scale (large
quantity).
(iii) Help to prove theoretical ideas and also to confirm the new
reaction mechanism.
FACTORS TO BE CONSIDERED IN ORGANIC SYNTHESIS
(1) Is the starting material available either for laboratory and
industrial scale?
(2) How convenient is the method of choice?
(3) Are the reagents that would be needed available?
For Industrial scale
(4) Is power available at all times?
(5) How much time is involved in the organic synthesis?
(6) Is the overall yield reasonable?
(overall yield is the mathematical product of the yields of the
individual steps).
(7) Is there available market for the product?
Organic synthesis can be: (a) partial organic synthesis and (b) total
organic synthesis.
Partial synthesis involved a few steps. In this case we make use of
products that is similar to the final product.
For example, to synthesize Compound A below using partial
synthesis, compounds like substituted benzene can be used as the
starting material. On the other hand, the total synthesis involves
more steps and a longer time.

OH

CH3

Compound A
 BASIC STRATEGIES FOR DEVISING SYNTHESIS OF
ORGANIC COMPOUNDS
i. Think backwards from the target material to the starting material. This is
called RETRO-SYNTHETIC REPRESENTATION. This means the full
structure of the organic compound must be known including the
stereochemistry, C-C skeleton, functional group, etc.
ii. There must be a comprehensive literature survey of the compound.
iii. Design possible synthetic routes based on what is found from literature.
iv. Break the compounds into synthons. SYNTHONS are fragments of
molecules with an associated polarity (usually a cation or anion represented
by ‘+’ or ‘-’) which stand for the reagents we are going to use in the forward
synthesis. X Y breaks to form X+Y- or X-Y+
This operation is called ‘Disconnection’
 SYNTHETIC ROUTES OF SELECTED COMPOUNDS

(1) Conversion of Acid functional group into an hydrazide

a. One step reaction procedure
Me
Me
OH
1) CDI, THF, Et3N NH
NH2
O
H3CO 2) NH2NH2 . H2O O
S-Naproxen 50 °C, 3 h H3CO
S-Naproxen hydrazide

b. Two step reaction procedure

Me Me
OH OMe
MeOH, 600C MeOH, 600C Me
O O NH2NH2.H20 NHNH2
H3CO Reflux, 12 hrs H3CO
S-Naproxen S-Naproxen ester Reflux, 12 hrs O
H3CO
S-Naproxen hydrazide
 O O
DPPA
R OH R N3
Carboxylic acid DCM, Reflux 6 hrs
Acyl azide

b. Two step reaction

O O O
SOCl2
NaN3 or Me3SN3
R OH R Cl R N3
Carboxylic acid DCM, Reflux 6 hrs Reflux, 5 hrs
Acid chloride Acyl azide