Condensation reactions

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 In Gluconeogenesis and Photosynthesis 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 .   U sed 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 L- cosamine , the carbohydrate subunit of the anthracycline class of antibiotics  (–)- 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: C oupling 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 + (CH 3 ) 3 CO - )

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

19. APPLICATION OF DARZEN’S REACTION Darzen’s reaction is used to produce fragrance chemicals, methyl nonyl acetaldehyde (Aldehyde C-12 MNA) na turally 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 . F or example two molecules of acetone condense to a single compound mesityl oxide in the presence of an ion exchange resin 2 CH 3 COCH 3 → (CH 3 ) 2 C=CH(CO)CH 3 + H 2 O 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 11 th and 12 th 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

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