Aim: To synthesise 2-methoxy-6-(p-tolyliminomethyl)-phenol by solvent free green condensation

reaction between o- vanillin and p-toluidine (Solvent-free synthesis of azomethine).

Estimated Time: 10-15 minutes

Basic Lab Operations: Recrystallisation, melting point determination.

Chemicals Required: o-vanillin, p-toluidine

Theory:

Green chemistry is the design of chemical products and processes that reduce or eliminate the use
or generation of hazardous substances. It reduces pollution at its source by minimizing or eliminating
the hazards of chemical feedstocks, reagents, solvents, and products. It applies across the life cycle
of a chemical product, including its design, manufacture, use, and ultimate disposal. Green chemistry
is also known as sustainable chemistry. It is a philosophy that applies to all areas of chemistry, not a
single discipline of chemistry.

Green chemistry prevents pollution at the molecular level by reducing the generation of harmful
substances. In doing so, it reduces the negative impacts of chemical products and processes on
human health and the environment. It does so by:

• Applying innovative scientific solutions to real-world environmental problems

• Lessening and sometimes eliminating hazard from existing products and processes

• Designing chemical products and processes to reduce their intrinsic hazard

A Schiff base is a nitrogen analog of an aldehyde or ketone in which the C=O group is replaced by
C=N-R group. The term is often synonymous with azomethine which refers specifically to
secondary aldimines (i.e. R-CH=NR' where R' ≠ H).These are usually formed by nucleophilic
addition -elimination reaction of an aldehyde or ketone with a primary amine according to the
following scheme:

Where R, may be an alkyl or an aryl group. Schiff bases of aliphatic aldehydes are relatively
unstable and readily polymerizable, while those of aromatic aldehydes having effective
conjugation are more stable. The formation of a Schiff base from an aldehydes or ketones is a
reversible reaction and generally takes place under acid or base catalysis, or upon heating.

The use of solvent free reaction or solid-solid reactions has emerged as a powerful tool in green
organic synthesis. These eco-friendly solid-state reactions obviate the use of organic solvents
 and bring about reduction of waste as well as energy which is in line with principles of green
chemistry. The ground-breaking work of scientists gave an insight to the fact that the reactions
can be carried out by just mixing the reactants without any solvent. Methods such as ball milling,
microwave reactions, mortar and pestle are few examples of existing technologies used for
carrying out solvent free reactions. Solvent free reactions using mortar and pestle are generally
limited to liquids or low melting solids that are able to form a melt on mixing. (A depression in
melting point is observed by mixing of two solid reactants. At times, this depression is enough to
melt it below room temperature and convert it into liquid called as melt.) This melt enables
individual molecules to gain required mobility leading to important reactive collisions which in
turns leads to rapid reaction between the two solid reactants. The present synthesis of
azomethine is an example of a solid-solid reaction of aromatic aldehydes like o-
vanilin/Vanilin/isovanilin /Salicylaldehyde etc. and aromatic amines like p-toluidene. Due to
extended conjugation, these compounds are usually coloured.

Azomethines are of great biological interest as antibacterial, antifungal agents etc.

Green Component of the reaction:

• The protocol discussed above is carried out under solvent-free conditions thereby
avoiding the use of any harmful, expensive organic solvent.
• The reaction is highly energy efficient.
• High atom economy as all the carbons of the reactant are converted into the product
• The reaction occurs rapidly under ambient conditions and isolation of product from
the byproduct (water) requires no additional heating or workup.

Chemical Reaction Involved:

Mechanism:
 Experimental Procedure: On a clean china dish place finely grounded p-toluidine (0.35 g) and o-
vanillin (0.50 g) and mix with the help of glass rod. On mixing, immediately an orange liquid is
formed. Keep on stirring with glass rod until a homogeneous dry powder is obtained. An orange
colored liquid is obtained which solidifies. Collect the crude product. Recrystallize a part of it from
ethanol.

Observations:

S. Mol. wt. Mol. wt. Mol. Wt. of Wt. of Expected Observed Atom % M.P. of
No. of R 1 of R 2 wt. of R1 R 2 used Yield/g Yield/g Economy Yield the
Product used product
1
2
3
4

Calculations:

𝑭𝒐𝒓𝒎𝒖𝒍𝒂 𝒘𝒆𝒊𝒈𝒉𝒕 𝒐𝒇 𝒕𝒉𝒆 𝒓𝒆𝒂𝒄𝒕𝒂𝒏𝒕

Result: - …………….g of 2-methoxy-6-(p-tolyliminomethyl)-phenol was obtained from the given

Note:
(a) Finely grounded starting materials should be used to maximise the surface area. Neither of the
two reactants will melt upon grinding individually.

(b) Mortar and pestle can also be used for carrying out the solid- state reaction.

(c) Difference between solid phase synthesis and solid-solid reaction: In solid phase synthesis the
compounds are attached with an insoluble inert polymeric material which allows them to be readily
separated from the reaction mixture. Whereas, in solid-solid synthesis, the reaction of two solids
takes place in absence of any solvent media.

References

• (Source: https://www.epa.gov/greenchemistry/basics-green-
chemistry#:~:text=Green%20chemistry%20is%20the%20design%20of%20chemical
%20products,Green%20chemistry%20is%20also%20known%20as%20sustainable%2
0chemistry.)
• https://shodhganga.inflibnet.ac.in/bitstream/10603/8812/6/06_chapter%201.pdf