These pages are designed to assist you with the learning of organic synthesis; like all
other problem-solving, practice is essential, so you should obtain as many of the
flow-type problems to do as you can.
Synthetic organic chemistry.
Reactions are of several types:
- those which make things; carbonyl compounds with HCN give useful products;
- those which test for things; carbonyl compounds with 2,4-dinitrophenylhydrazine
give a yellow precipitate;
- some reactions do both; the haloform reaction is used to test for CH3CO-
of CH3CHOH, and it is also used to make chloroform CHCl3 commercially;
bromine is used to test for alkenes but the same reaction is used as a route to diols.
Uses of organic synthesis:
- commercial production of necessary compounds on a large scale;
- the small-scale production of compounds needed in research, perhaps a range of slightly
different compounds which are not commercially available;
- confirmation by synthesis of the structure of naturally occurring molecules.
- Heavy' organic: this involves the production of large quantities of relatively
- Small-scale organic: the production of perhaps only a few tons of substance, which might
be relatively simple;
- Natural products: the extraction and use in synthesis of complex compounds from plants
or animals, usually on a small scale;
- Pharmaceuticals: production of these could use all the above sources to give moderate
quantities of quite complex compounds.
Synthetic routes available include the following, which need careful selection:
- interconversion of functional groups, e.g. conversion of a halogenoalkane RCH2Cl
to an alcohol RCH2OH.
- making C-C bonds, e.g. reaction of halogenoalkane with CN - ion
- breaking C-C bonds, e.g. the conversion of CH3COCH3 to CHI3 and
- some routes which look good on paper may not be useful in practice.
Selecting a particular route:
There may be several routes to a compound. Some routes may not be possible or desirable
- too many steps - the more steps there are the higher the yield has to be at each step. A
yield of 80% is good per step: a four step reaction would give an overall yield of 41%,
which would be made poorer by handling losses. Many reactions have much lower yields than
- poor yield may come from competing reactions, or the reaction may be an equilibrium.
- yields from equilibrium reactions can sometimes be improved by changing the conditions
- the products from competing reactions may or may not be useful
- competing reactions, giving other products which might be difficult or expensive to
separate from the main product.
- stereochemical problems: chiral starting materials may have their configuration inverted
or the product mixture may be racemic;
- non-availability of starting materials, or the expense of their synthesis.
Starting materials available in large quantities include: alkanes, alkenes, lower
alcohols, lower halogenoalkanes, lower aldehydes and ketones, benzene and various
The choice of reagents and conditions:
The reagents and conditions to produce a given material in industry are often different
from those used in the lab
- lab processes may be too expensive for industrial use: some laboratory reagents are very
- many laboratory reactions give useless by-products which may be difficult or hazardous to
dispose of in quantity. Thus oxidation reactions in the laboratory would probably use acidified
potassium dichromate producing chromium(III) salts or potassium manganate(VII) giving
manganese(II) salts; industry would prefer to use air or oxygen and not have the salts to
dispose of. Thus ethane-1 ,2-diol, used as anti-freeze and hydraulic fluid, can be made by
the action of potassium manganate(VII) in alkaline solution on ethene. A sludge of
manganese(IV) oxide also results. Industrially, ethene is oxidised to epoxyethane with air
at 300oC and a silver catalyst, the epoxy compound then being hydrolysed. There
are no products other than the diol. The manganese-containing product is waste; epoxyethane
can be used for other things as well as conversion to ethan-1,2-diol.
The practical techniques are not peripheral to a synthetic process; careful choice of
technique can make or break a synthetic pathway. Techniques used in reaction and
- heating under reflux (NOT just reflux')
- distillation and fractional distillation
- recrystallisation and filtration
- solvent extraction
Techniques used in analysis:
- melting temperature and mixed melting temperature
- elemental analysis (empirical formula)
- relative molecular mass determination and mass spectra
- other spectra: ultraviolet, infrared, nuclear magnetic resonance
Safety will need to be considered: this must be with regard to specific hazards, not in
vague terms like 'wear goggles and lab coat':
- volatility and flammability
- volatility and toxicity by inhalation
- toxicity by skin absorbtion
- the scale of the preparation is significant - small quantities of a toxic material may
present less of a hazard than large quantities of a merely harmful one.
Problem-solving in synthetic chemistry.
Problems in synthesis may be
- free-response; you have to obtain a given material but the choice of reactions is left
- flow-type problems, where some data on the intermediates is given. Usually you will
know the starting material, or at least the class of compound to which it belongs, and you
will know the substance required.
- Write all the information given on a flowchart
- Start at the end: often information about possible isomers is given last; if you
commit yourself too early to a number of structures you will be reluctant to change them
no matter how strong the later evidence is that you should!
- Synthetic pathways could well include compounds you have never met before; it's the
principles of the interconversions that are being addressed.
- Do not include mechanisms unless they are asked.
Scheme 1 summarises the relationships between some
classes of organic substance.
- Make a large copy of this, then
- fill in the reagents and conditions that are used at each step
- choose the simplest example that will work and write the equation for a typical
Scheme 2 summarises the relationships between some
The reactions fall into two classes;
- Reactions on the ring;
- Reactions of the side-chains; these on the whole resemble similar reactions in aliphatic
The first illustrates the point about not deciding on structures too early; the
second gives both ring and side-chain reactions of aromatic compounds, and shows that
several ways of doing things are often possible.
Compound A, C3H80, gives steamy fumes when reacted with
phosphorus pentachloride. On oxidation with acidified potassium dichromate solution A
gives B, C3H60. This, with methylmagnesium bromide under
suitable conditions, gives C, C4H10O. C does not react
with acidified potassium dichromate solution. Treatment of C with excess hot
concentrated sulphuric acid gives D, C4H8, which on reaction
with hydrogen bromide gives mainly 2-bromo-2-methylpropane. Find the structures of A
to D, giving reasons and equations for the reactions which occur.
Benzene C6H6 and chloromethane CH3Cl react in the
presence of aluminium chloride to give A, C7H8. A
reacts with chlorine in sunlight to give B, C7H7Cl, which
reacts with aqueous sodium hydroxide to give C, C7H8O. Mild
oxidation of C gives D, C7H6O, which with
2,4-dinitrophenylhydrazine gives an orange precipitate. Further oxidation of D
gives E, C7H6O2, which can also be produced from A
by vigorous oxidation with alkaline potassium manganate(VII) solution.
The reaction of B with potassium cyanide under suitable conditions gives F,
C8H7N, which in turn can be reduced to G, C8H11N.
Identify the substances A to G, giving reasons for your choice and
writing equations for the reactions that occur.
Write the mechanism for the reaction between benzene and
chloromethane. Suggest another series of reactions by means of which you could convert F