Various condensation reaction in fragrance industry

1. CONDENSATION
REACTION
Prasad Jitkar
Sundaralakshmi V.

2. Condensation reaction
• Definition: A reaction in which two or more molecules combine to
form a larger molecule, with the simultaneous loss of a small
molecule such as water or methanol, while this occurs in many
reactions, the term is usually reserved for reactions in which a new
carbon-carbon bond is formed.

3. Aldol Condensation
• Aldol Condensation can be defined as an organic reaction in which
enolate ion reacts with a carbonyl compound to form β-
hydroxyketone or β-hydroxyaldehyde, followed by a dehydration to
give a conjugated enone. Aldol Condensation plays a vital role in the
organic synthesis, creating a path to form carbon-carbon bonds.

4. Step by step Mechanism of Aldol Condensation
A) The hydroxide ion deprotonates the aldehyde.
B) Here Enolate ion 1 adds to the unreacted aldehyde.
C) Alkoxide ion 2 is protonated by water.

5. Application of Aldol Condensation
1) In Gluconeogenesis and Photosynthesis
2) It works as an intermediate for the production of perfumes such as
pseudomethylionone (cyclized to methylionone), alpha-amylcinnamic aldehyde,
alpha-hexyl cinnamic aldehyde, alkyl-a-methyldihydro cinnamic aldehydes and
cinnamic aldehyde.
3) Used in the manufacture of pharmaceuticals, such as a, b unsaturated ketones
and the aromatic ketones known as chalcones. It is also generally used to create
plasticizers.

6. alpha-amyl cinnamic aldehyde- Sweet, floral, fruity, tropical and green with a powdery nuance
Pseudomethylionone- Not known used in cosmetics
alpha-hexyl cinnamic aldehyde- fresh floral green jasmin herbal waxy
alkyl-a-methyl dihydro cinnamic aldehydes- balsam sweet
cinnamic aldehyde- Cassia, cinnamon, cinnamon bark and red hots

7. Perkin reaction
• It gives an α,β-unsaturated aromatic acid by the aldol condensation of an
aromatic aldehyde and an acid anhydride, in the presence of an alkali salt of
the acid. The alkali salt acts as a base catalyst, and other bases can be used
instead.
• Reaction of Salicylic aldehyde and acetic anhydride involves the formation of an
aldol followed by dehydration and lactonization and gives coumarin. (Odor-
sweet, stinging, coconut note)

8. Mechanism of Perkin reaction

9. Henry reaction (Henry nitroaldol reaction)
• The Henry reaction is an organic reaction used to convert a
nitroalkane with an α-hydrogen and an aldehyde or ketone to a β-
nitro alcohol using a base catalyst.
Synthesis of
1) L-cosamine, the carbohydrate subunit of the anthracycline class of antibiotics
2) (–)-bestatin used in treatment of acute myelocytic leukemia and lymphedema

10. Stobbe reaction
• Synthesis of Napthol and Indenone derivatives
• Tetralone derivatives
• Phenanthrene derivative
Application

11. Esterification reaction

12. Benzoin Condensation
• The Benzoin Condensation is a coupling reaction between two
aldehydes that allows the preparation of α-hydroxyketones. The first
methods were only suitable for the conversion of aromatic aldehydes.
 This reaction is helpful in the synthesis of heterocyclic compounds and also extends to the
aliphatic form of aldehydes.
 These reactions also find its applications in the poly chemistry, for the production of
polymers as well in the condensation of new monomers
Applications

13. Acyloin condensation:
Coupling of two carboxylic esters using metallic sodium to yield an α-hydroxyketone (Acyloin)
Preparation of cyclic acyloins – This condensation has been used for preparation cyclic
acyloins. Long chain dicarboxylic esters have been converted to large ring compounds
without the use of dilution technique. It is used best for closing rings of ten members or
more.
Preparation of CATENANE – CATENANE is a very interesting & unique compound with
interlocking rings. It is formed when acyloin condensation was employed for ring
closure with esters of 34-carbon dicarboxylic acids.
Applications

14. Pechmann Condensation (Coumarin Synthesis):
The Pechmann Condensation allows the synthesis of coumarins by reaction of phenols with
β-keto esters
With highly activated phenols such as resorcinol, the reaction can be performed under much
milder conditions which provides a useful route to umbelliferone derivatives.

15. Condensation polymers
• Any kind of polymers formed through a condensation reaction—
where molecules join together—losing small molecules as byproducts
such as water or methanol, as opposed to addition polymers which
involve the reaction of unsaturated monomer
• Nylon, a very common condensation polyamide, can be produced by
reacting di-amides with dicarboxylic acids

16. DNA formation

17. DARZEN’S CONDENSATION
The Darzen’s gylicidic ester condensation involves the condensation of an
aldehyde or ketone with a α-halo ester to produce an α,β- epoxy
ester(glycidic ester). The most frequently used condensing agents anre
sodium ethoxide or potassium-tertiary butaoxide(K+(CH3)3CO-
)

18. Mechanism:
(K+(CH3)3CO-
)

19. APPLICATION OF DARZEN’S
REACTION
• Darzen’s reaction is used to produce fragrance chemicals, methyl
nonyl acetaldehyde (Aldehyde C-12 MNA) naturally occurs in citrus
oils and ethyl methyl phenyl glycidate or strawberry glycidate (
Aldehyde C-16).
Aldehyde C -
16

20. SCHIFF BASES
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. It is usually formed by
condensation of an aldehyde or ketone with a primary amine.

21. MECHANISM

22. APPLICATION
Aurantiol (Methyl Anthranilate Schiff's Base).
Aurantiol is perhaps the best known Schiff base and is extensively used in a large
variety of floral notes such as orange-blossom,
Helioforte(Methyl Anthranilate Schiff's Base).
Fresh, airy, floral-orangeblossom, ozone, green-leafy. Very diffusive

23. CLAISEN CONDENSATION
 The condensation of between esters is known as the Claisen
condensation. It is important to note that an equivalent amount of base
must be employed for this reaction.
 Claisen condensation is the main method for preparing beta-ketones

24. APPLICATION
Ethyl aceate undergoes Claisen condensation on treatment with sodium
ethoxide to give a β-keto ester known by its common name ethyl
acetoacetate (also called acetoacetic ester) – colourless liquid with fruity
odour

25. INTRAMOLECULAR CLAISEN CONDENSATION:
THE DIECKMANN REACTION
 Esters of dicarboxylic acids undergo an intramolecular version of the
Claisen condensation when a five- or six-membered ring can be formed.
 Intramolecular Claisen condensation of diesters in presence of a base is
Dieckmann cyclisation.
 Mechanism is similar to Claisen condensation

26. KNOEVENAGEL CONDENSATION
The Knoevenagel condensation is an organic reaction used to convert an aldehyde
or ketone and an activated methylene to a substituted olefin using an amine base
as a catalyst.
 Active methylene compound in the reaction can be diethylmalonate,
ethylacetoacetate or malonic acid.
 Weakly basic conditions can be maintained by use of pyridine or piperidine in
reaction

27. GUARESCHI–THORPE CONDENSATION
Condensation of 1,3-dicarbonyl compounds with cyanoacetic ester in the
presence of ammonia or directly with cyanoacetamide, known as Guareschi-
Thorpe condensation, lead to the formation of 2-pyridone derivatives.

28. SELF- CONDENSATION
 Self-condensation is an organic reaction in which a chemical compound
containing a carbonyl group acts both as the electrophile and the
nucleophile in an aldol condensation. It is also called a symmetrical aldol
condensation.
 For example two molecules of acetone condense to a single compound
mesityl oxide in the presence of an ion exchange resin
2 CH3COCH3 → (CH3)2C=CH(CO)CH3 + H2O
 For synthetic uses, this is generally an undesirable, but spontaneous and
favored side-reaction of mixed aldol condensation, and special precautions
are needed to prevent it.

29. REFERENCES
 11th and 12th standard NCERT book
 https://www.organic-chemistry.org/namedreactions
 Book- Perfumes art, science and technology by Muller
 ChemDraw
 Organic Chemistry by Francis A. Carey 4 th Edition
 Fundamental Aliphatic Chemistry P. W. G. SMITH and A. R. TATCHELL
 Name Reactions -A Collection of Detailed Reaction Mechanisms Authors:
Li, Jie Jack