CLEMMENSEN REDUCTION

About Clemmensen Reduction

The reduction of carbonyl groups of aldehydes and ketones to methylene groups with amalgamated zinc and
concentrated hydrochloric acid is known as Clemmensen reduction.

The reduction of carbonyl groups of aldehydes and ketones to methylene groups with amalgamated zinc and
concentrated hydrochloric acid is known as Clemmensen reduction.

1. The reduction consists in refluxing the carbonyl compounds with amalgamated zinc and excess of
concentrated hydrochloric acid.
2. The reduction is useful especially for ketones containing phenolic or carboxylic groups which remain
unaffected. Ketones are reducing more often than aldehydes.
3. This reduction is also observed in Wolff-Kishner reduction but Clemmensen reduction is easier to
perform.
4. The reduction, however, fails with acid-sensitive and high molecular weight substrates. The α, β-
unsaturated ketones undergo reduction of both the olefinic and carbonyl groups.

Reaction Mechanism of Clemmensen Reduction

Exceptional behaviour of clemmensen reductions

Certain cyclic 1,3-diketones give under Clemmensen reduction a fully reduced product along with a
monoketone with ring contraction.

The latter probably is formed through a diradical with subsequent intramolecular C – C bond formation and
pinacol type rearrangement.
ALDOL CONDENSATION
About Aldol condensation
Two molecules of an aldehyde or a ketone undergo condensation in the presence of a base to yield a β-
hydroxyaldehyde or a β-hydroxyketone. This reaction is called the aldol condensation which may be
exemplified by the reaction of acetaldehyde to give acetaldol (3-hydroxybutanal).

The mechanism of this reaction illustrates important characteristics of carbonyl compounds, i.e. the acidity of
their α hydrogens and the tendency of their carbonyl groups to undergo nucleophilic addition.Befor moving to
mechanism of aldol read the basics of organic chemistry and class 12th chemistry
Let us see the mechanism now:

Reaction Mechanism of Aldol condensation

Step 1.
Base abstracts a proton from the α carbon of aldehyde to give resonance stabilized enolate ion.

Step 2.

The enolate ion then acts as nucleophile and attacks the carbonyl carbon of a second molecule of aldehyde,
producing alkoxide ion.

Step 3.

In step 1, OH– is acting as a base and not as a nucleophile. OH– will act as a nucleophile and attack to the
carbonyl group only when there is no acidic hydrogen, i.e. its (OH–) first preference is to act as a base and
then as a nucleophile.
This reaction can also be catalysed by acid. Let us see this mechanism and the product formed.
Crossed Aldol Condensation

An aldol condensation between two different carbonyl compounds so called crossed aldol condensation is not
always useful as a mixture of four different possible products may be obtained. under certain conditions, a
good yield of a single product can be obtained from a crossed aldol condensation.
One reactant contains no α-hydrogens and therefore is incapable of condensing with itself (e.g. aromatic
aldehydes or formaldehyde).
Intramolecular Aldol Condensation

When a compound has two carbonyl groups, it can undergo intramolecular aldol condensation in the
presence of dilute base (if a-H atoms are present in the compound).
An intramolecular reaction is readily favoured if the reaction leads to the formation of a 5 or 6-membered ring.
When one of carbonyl group is an aldehyde and other is a ketone, it’s the ketone, which forms carbanion and
this carbanion attack the carbonyl group of an aldehyde in such a manner that 5 or 6-membered ring is
formed. For example, 2, 5-hexanedione in presence of dilute OH- undergoes intramolecular aldol
condensation to give 2 set of products as there are 2 different types of a-hydrogens. One of the product has a
5-membered ring and the other has a 3-membered ring. The major product of the reaction is a 5-membered
ring compound as 5-membered ring has greater stability than 3-membered ring.

Mechanism of Intramolecular Aldol condensation

ARNDT−ESTER SYNTHESIS
Arndt-Ester synthesis
This method is used to convert lower carboxylic acid into higher carboxylic acid.

RCO2H → RCOCl RCONH2 RCH2CO2H

Arndt-Ester synthesis Mechanism

Nucleophilic attack of diazomethane on the carbonyl carbon of the acid chloride gives an intermediate (i)
which eliminates a molecule of HCl to give diazoketone (ii) Diazoketone then splits off a molecule of nitrogen
to form a carbene (iii) which rearranges to ketene. The highly reative ketene readily reacts with the nuclephile
present (H2O) to form the next higher acid.
For more detail about the example and questions of Arndt ester synthesis read the complite theory
of carboxylic acid chapter

Examples of Arndt−Ester synthesis

BAEYER−VILLIGER OXIDATION
Detail Reaction of Baeyer-Villiger Oxidation
Baeyer-Villiger Oxidation involves the oxidation of ketones to esters by the treatment with peroxyacids.

Cyclic ketones are converted to lactones with ring expansion.

The overall reaction is an insertion of oxygen atom between the carbonyl group and the adjacent carbon atom
in ketone. It involves the migration of a group from carbon to the electron−deficient oxygen. Organic solvents
(inert) are used such as glacial acetic acid or chloroform, which can dissolve the reactant.

Baeyer-Villiger Oxidation Mechanism

First of all the peroxyacid protonates the ketone and then peroxyacids undergoes nucleophilic attack on this
protonated ketone to form an peroxide intermediate (A). This intermediate then undergoes loss of carboxylate
anion and migration of a group from carbon to electron deficient oxygen to yield the protonated ester (B). This
finally losses a proton to give an ester.

Application of group in Baeyer-Villiger Oxidation

The presence of electron releasing groups in the ketone and electron withdrawing groups in the peroxyacids
increases the rate of reaction. In unsymmetrical ketones that group migrates which is more electron releasing,
thus the migratory aptitude of alkyl groups is in the order 3° > 2° > 1° > CH3.

Electron releasing substituents in the aryl group facilitate migration. The migratory order of aryl groups is
p−anisyl > p−tolyl > phenyl > p−chlorophenyl > p−nitrophenol.

In case of alkyl aryl ketones, it is the aryl group which migrates (except in case of tert butyl groups).

Example of Baeyer−Villiger Oxidation

BENZOIN CONDENSATION
Reaction Mechanism of Benzoin Condensation
This reaction of aromatic aldehydes, ArCHO, resembles the Cannizzaro reaction in that the initial attack is by
an anion (-CN) on the carbonyl carbon atom of one molecule, but instead of hydride transfer it is now
converted to carbanion which undergoes addition to the carbonyl carbon atom of the second molecule of
ArCHO. The rate law commonly observed is

Rate = k [ArCHO]2 [-CN]

and the Benzoin Condensation is believed to follow the general pathway as

Mechanism of Benzoin Condensation

When aromatic aldehyde is treated with alcoholic KCN, the product is not a cyanohydrin but hydroxy aromatic
ketone called benzoin. The product of aromatic aldehydes with KCN is different than aliphatic aldehydes
because after the attack of CN-, the intermediate (I) in aromatic aldehyde has sufficient acidity (due to -I effect
of Ph) so that intramolecular proton exchange takes place to form a carbanion, which is resonance stabilized.
This carbanion then attacks another molecule of aromatic aldehyde, which undergoes intramolecular proton
exchange and then ejection of CN- to give final product i.e. benzoin. The rate limiting step of the reaction is
attack of carbanion on second molecule of aromatic aldehyde.
Example of Benzoin Condensation

In which of the following substrate, rate of Benzoin condensation will be maximum?

Benzoin condensation is due to stability of intermediate (III) when negative charge on C is extensively
delocalised in benzene ring, Nitro and CN group. In all other cases, such dispersal is not extensively possible.
On the other hand, NO2- is also creating positive charge centre on carbonyl carbon, making it more
susceptible to nucleophilic attack of CN-.
Therefor correct answer is (A)

List of Name Reaction of Organic Chemistry consist of detail Reaction Mechanism of all name reactions of
Organic Chemistry.

BECKMANN REARRANGEMENT
About Beckmann Rearrangement
The acid-catalyzed conversion of ketoximes to N-substittued amides is known as Beckmann
rearrangement. The reaction is catalyzed by acidic reagents like H2SO4, SOCl2, SO3, PCl5, P2O5, C6H5SO2Cl
etc. The reaction involves the migration of a group from carbon to the electron deficient nitrogen.The
migration of the groups does not depend on the migratory aptitude but upon the orientation of the group is
relation to the -OH group. It is found that the migrating group is always anti (trans) to the hydroxyl group. Thus
the reaction is stereospecific.

Reaction Mechanism of Beckmann Rearrangement

The mechanism of the above reaction has been outlined as
In strong acids, the reaction proceeds with the protonation of the OH group of the oxime with subsequent loss
of water to yield(A) with electron deficient nitrogen. The migration of alkyl group then gives a carbocation,
which is attacked by water molecule followed by the loss of proton gives the amide.
The migrating group retains its configuration and hence the migrating group does not become completely free
during the migration, otherwise the reaction cannot be stereospecific. Thus the migration and breaking of N-O
bond may be concerted (taking place in one step).For example,

Solved Example of Beckmann Rearrangement

Questions based on Beckmann rearrangement

List of Name Reaction of Organic Chemistry consist of detail Reaction Mechanism of all name reactions of
Organic Chemistry.

CANNIZZARO REACTION
About Cannizzaro Reaction
Those aldehydes (aliphatic or aromatic), which do not have a-hydrogen atom on treatment with strong base
undergoes a reaction involving its 2 moles, one getting oxidised to yield acid salt and the other getting
reduced to primary alcohol. The important condition is that there should not be a good leaving group attached
to the carbonyl group.

Reaction Mechanism of Cannizzaro Reaction

This involves hydride transfer from an aldehyde molecule lacking an α-H atom e.g., HCHO, R3CCHO, ArCHO,
to a second molecule of either the same aldehyde (disproportionation) or sometimes to a molecule of different
aldehyde (crossed Cannizzaro). The reaction requires the presence of strong bases.

The step by step mechanism of Cannizzaro Reaction are

Mechanism of Cannizzaro Reaction at High concentrantion of NaOH

Rapid and reversible addition of -OH to PhCHO yields the hydride donor species, this is followed by slow, rate
limiting hydride transfer to the carbonyl carbon atom of a second molecule of PhCHO, and the reaction is
completed by rapid proton exchange to yield the more stable pair of carboxylate and alcohol. Mutual
oxidation/reduction of two molecules of aldehyde has thus taken place to yield one molecule each of the
corresponding carboxylate anion and of the primary alcohol.

Example of Cannizzaro Reaction

Crossed Cannizzaro reaction

The Cannizzaro reaction between two dissimilar aldehyde moelcuels (crossed Cannizzaro reaction) may yield
all possible products. However, when one of the aldehydes is formaldehyde the formate ion and the alcohol
corresponding to the other aldehyde are formed exclusively. The exclusive formation of the formate ion is due
to the high reactivity of formaldehyde which preferentially adds a hydroxide ion before losing one of its two
hydrogens as hydride ion to the less reactive aldehyde.

Intramolecular Cannizzaro
Questions based on Cannizzaro Reaction
List of Name Reaction of Organic Chemistry consist of detail Reaction Mechanism of all name reactions of
Organic Chemistry.
Mechanism of Important Name Reactions
1. Aldol Condensation: We can define aldol condensation as an organic reaction in which an enolate ion reacts with a
carbonyl compound to form β-hydroxy aldehyde or β-hydroxy ketone, followed by dehydration to give a conjugated
enone.
2. Balz-Schiemann Reaction: The Balz-Schiemann Reaction is named after German scientists Günther Schiemann
and Günther Balz. The reaction showcases the conversion of arylamines to aryl fluorides. The reaction happens
through diazotization after which thermal decomposition of the derived hexafluorophosphate or tetrafluoroborates.
Visit Balz-Schiemann Reaction for more information.
3. Cannizzaro Reaction: The Cannizzaro Reaction is named after Stanislao Cannizzaro. The chemical reaction
signifies the base-induced disproportionation of a non-enolizable aldehyde. Click here for more information
on Cannizzaro Reaction.
4. Clemmensen Reduction: The Clemmensen Reduction reaction is named after a Danish scientist, Erik Christian
Clemmensen. The Clemmensen Reduction reaction shows how to reduce ketones or aldehydes to alkanes using zinc
amalgam and hydrochloric acid.
5. Etard Reaction: The Etard Reaction is named after a French chemist named Alexandre Léon Étard. The Etard
Reaction is a chemical reaction in which a heterocyclic bound or an aromatic methyl group is directly oxidized to an
aldehyde using chromyl chloride. Visit Etard Reaction for more information.
6. Finkelstein Reaction: The Finkelstein Reaction is named after Hans Finkelstein, a German chemist. The Finkelstein
Reaction deals with the exchange of a halogen atom by a Substitution Nucleophilic Bimolecular reaction. Click here
for more information on Finkelstein Reaction.
7. Friedel Crafts Reaction: Friedel Crafts Reaction was developed by Charles Friedel and James Crafts in 1877. The
Friedel – Crafts Reaction is a way of attaching substituents to an aromatic ring. Visit Friedel Crafts Reaction for an in-
depth explanation of the reaction details and mechanism.
8. Gabriel Phthalimide Synthesis: Gabriel Phthalimide Synthesis was discovered by a German chemist named
Siegmund Gabriel. The Gabriel synthesis is a chemical reaction used to obtain primary amines from primary alkyl
halides.
9. Gattermann Reaction: The Gattermann Reaction is named after a German chemist, Ludwig Gattermann. Also known
by the name, Gattermann salicylaldehyde synthesis is a chemical reaction in which aromatic compounds in the
presence of a Friedel–Crafts catalyst are formylated by hydrogen cyanide.
10. Gattermann – Koch Reaction: The Gattermann–Koch reaction is named after the German chemists Julius Arnold
Koch and Ludwig Gattermann. In a Gattermann–Koch reaction refers to a Friedel–Crafts acylation reaction in which a
Friedel–Crafts catalyst, hydrochloric acid, and carbon monoxide are used to produce aromatic aldehydes from various
aromatic compounds, including derivatives of naphthalene and benzene. Click here for an in-depth explanation of the
reaction details and mechanism of Gattermann – Koch Reaction.
11. Grignard Synthesis: A Grignard Synthesis Reaction is a chemical reaction in which vinyl, alkyl, or aryl-magnesium
halides (Grignard reagents) add to a carbonyl group of a ketone or aldehyde. Visit Grignard Synthesis for more
information.
12. Kolbe’s Reaction: Kolbe’s Reaction is a chemical reaction where aromatic hydroxy acid is produced from the heating
of sodium phenoxide with carbon dioxide under a pressure of about 100 atmospheres and the successful treatment of
the resulting product with sulfuric acid. Click here for an in-depth explanation of the reaction details and mechanism of
Kolbe’s Reaction
13. Reimer- Tiemann Reaction: Reimer- Tiemann Reaction was discovered by Karl Reimer and Ferdinand Tiemann.
They have a private track to test the used for the ortho-formylation of phenols. Visit Reimer- Tiemann Reaction for
more information.
14. Rosenmund Reduction: The Rosenmund reduction was named after Karl Wilhelm Rosenmund, who in 1918
reported its discovery. A hydrogenation process in which an acyl chloride is selectively reduced to an aldehyde.
15. Sandmeyer Reaction: The Sandmeyer Reaction was named after Traugott Sandmeyer in 1884. Sandmeyer Reaction
is a chemical reaction in which we use aryl diazonium salts to synthesize aryl halides. Sandmeyer Reaction provides
the capability of performing some unique transformations to benzene such as hydroxylation, trifluoromethylation,
cyanation, and halogenation.
16. Stephen Reaction: Also known by the name, Stephen aldehyde synthesis, was discovered by Henry Stephen. This
chemical reaction involves the preparation of aldehydes from nitriles using tin(II) chloride, hydrochloric acid and
quenching the resulting iminium salt with water. During the synthesis, ammonium chloride is also produced. Click here
for an in-depth explanation of the reaction details and mechanism of Stephen Reaction.
17. Swartz Reaction: Swarts reaction and Finkelstein reactions are halogen exchange reactions that are associated with
alkyl halides. Visit Swartz Reaction for more details.
18. Williamson Synthesis: This a chemical reaction to implement ether synthesis discovered by Alexander Williamson in
1850. The Williamson ether synthesis is a chemical reaction for forming an ether from an organohalide and
deprotonated alcohol.
19. Wolff – Kishner Reduction: The Wolff – Kishner Reduction reaction was first reported by Nikolai Kishner in 1911
and Ludwig Wolff in 1912. This is a named reaction in organic chemistry involving obtaining methylene groups by
converting carbonyl functionalities. Click here for an in-depth explanation of the reaction details and mechanism
of Wolff – Kishner Reduction.
20. Wurtz Reaction: The Wurtz reaction, named after Charles-Adolphe Wurtz, is a coupling reaction in organic
chemistry, organometallic chemistry and recently inorganic main group polymers, whereby two alkyl halides are
reacted with sodium metal in dry ether solution to form a higher alkane. Visit Wurtz Reaction for more information.
21. Wurtz – Fittig Reaction: The Wurtz–Fittig reaction is the chemical reaction of aryl halides with alkyl halides and
sodium metal in the presence of dry ether to give substituted aromatic compounds. Click here for more information
on Wurtz Fittig Reaction.
22. Carbylamine Reaction: The Carbylamine reaction is also known as Hofmann isocyanide synthesis. It is the reaction
of a primary amine, chloroform and a base to synthesize isocyanides. Click here for an in-depth explanation of the
reaction details and mechanism of Carbylamine Reaction.
23. Fischer Esterification: Fischer Esterification is an organic reaction which is employed to convert carboxylic acids in
the presence of excess alcohol and a strong acid catalyst to give an ester as the final product. Visit Fischer
Esterification for more information.
24. Haloform Reaction: The Haloform reaction is a chemical reaction where haloforms are produced by the exhaustive
halogenation of methyl aldehyde or methyl ketone with a base present. Click here for more information on Haloform
Reaction.
25. Hell-Volhard-Zelinsky Reaction: The Hell-Volhard-Zelinsky reaction is used for the halogenation of carboxylic acids
at the alpha carbon. Click here for an in-depth explanation of the reaction details and mechanism of Hell-Volhard-
Zelinsky Reaction.
26. Hoffmann Bromamide Reaction: The Hoffmann Bromamide reaction is used for the conversion of a primary amide
to a primary amine with one less carbon atom.