deep
TRANSCRIPT
AdiChemistry Home
NAMED ORGANIC REACTIONS
Named organic reactions are an important part of study of modern synthetic organic chemistry. Since these
reactions are mostly generalized are not only important from the view point of an academician but also play a
crucial role for a practicing organic chemist in developing his/her routine modern organic synthetic strategies.
These are named after the scientist(s) who did an extensive study of their reaction mechanism pathways, general
applicability and laboratory methods.
You can navigate to the desired named organic reaction from the following list.
Aldol addition reaction & condensation
Arndt-eistert reaction Exercises
Baeyer villiger oxidation Exercises
Bamford-Stevens reaction
Beckmann rearrangement Exercises
Birch reduction Exercises
Cannizzaro reaction
Clemmensen reduction
Favorskii rearrangement Exercises
Finkelstein reaction
Fittig reaction
Friedel-Crafts alkyation
Grignard reaction
Hunsdiecker reaction (Borodine reaction)
Mannich reaction
Michael addition reaction Exercises
Phillips condensation
Reformatsky reaction Exercises
Swern oxidation
Williamson's synthesis Exercises
Wittig reaction
Wolff-Kishner reduction
Wurtz reaction
Wurtz-Fittig reaction
AdiChemistry Home
NAMED ORGANIC REACTIONS
Table of contents Arndt Eistert-Explanation >
ALDOL ADDITION & CONDENSATION REACTION
The Aldol addition reaction involves the addition of α-carbon of an enolizable aldehyde or ketone to the
carbonyl group of a second aldehyde or ketone and thus by giving a β-hydroxy carbonyl compound also known as
an aldol (indicating both aldehyde and alcohol groups). The reaction is catalyzed more commonly by a base or
some times by an acid.
If the β-hydroxy carbonyl compound containing an α-hydrogen undergoes subsequent dehydration to yield an
α,β-unsaturated carbonyl compound, the entire process is also called as Aldol condensation. The dehydration
step is possible under the aldol reaction conditions or mostly carried out by heating in presence of an acid or
sometimes during acidic workup.
This reaction is a powerful means of making carbon-carbon bonds. The new C-C bond formed is shown in red
color in above reaction sequence.
MECHANISM OF ALDOL REACTION
In basic medium:
* The first step in base catalyzed aldol reaction is the abstraction of an α-hydrogen from the enolizable
carbonyl compound to give a resonance stabilized enolate anion. Usually this step is slow and rate determining.
*The next step is the nucleophilic addition of enolate anion to the carbonyl group of another aldehyde or
ketone molecule. The final product formed after protic workup is a β-hydroxy carbonyl compound (an aldol).
Note: In aldol reaction, the enolizable aldehyde or ketone acts as nucleophile, whereas the carbonyl group of
other molecule acts as electrophilic centre.
In acidic medium:
* Initially an enol is generated from the enolizable carbonyl compound during the acid catalyzed aldol reaction.
* Thus formed enol reacts with the protonated carbonyl group of another molecule.
Dehydration:
The dehydration of β-hydroxy carbonyl compound containing an α-hydrogen may be possible under the aldol
reaction conditions or by heating in acid medium. The formation of stable α,β-unsaturated carbonyl compound is
the driving force for this step.
Dehydration in basic medium:
Dehydration in acidic medium:
ALDOL REACTION CONDITIONS & CONTROL OF THE PRODUCT MIXTURE
Both the aldol reaction and condensation are reversible. In aldol reactions between two molecules of the same
aldehyde are generally quite successful, since the equilibrium lies far to the right, and the yields are very high.
E.g. The formation of aldol (β-hydroxy butyraldehyde) from two molecules of acetaldehyde and subsequent
dehydration to crotonaldehyde occurs readily in presence of a base like NaOH or Na2CO3; or an acid like HCl.
Note: There are two geometric isomers (i.e., E and Z) possible for crotonaldehyde.
However the equilibrium lies to the left incase of ketones. The equilibrium is to be shifted to the right to
achieve satisfactory yields by adjusting the reaction conditions. A Soxhlet extractor is generally employed to serve
this purpose.
A mixture of products is formed incase of unsymmetrical ketones if both the groups have α-hydrogens.
However such ketones react preferentially at less hindered side.
E.g. The major addition product formed when 2-butanone is treated with a base is shown below.
Note: However, each of above addition products undergoes dehydration easily by giving E & Z isomers of
corresponding α,β-unsaturated carbonyl compound. Thus four isomeric α,β-unsaturated carbonyl compounds are
formed in the reaction upon completion of reaction.
Crossed aldol reactions (Claisen–Schmidt reactions):
A mixture of addition products are formed when two different enolizable carbonyl compounds are subjected to
aldol reaction conditions.
For example, four different aldols are formed (without considering the stereoisomers), when two different
enolizable aldehydes are reacted i.e., two aldols from reaction between molecules of the same aldehyde and two
crossed aldol products from different aldehyde molecules.
E.g. When a mixture of acetaldehyde and propionaldehyde are treated with a base, a mixture of four addition
products are formed as shown below.
Again, each of these addition products gives two geometrical isomers upon dehydration.
ILLUSTRATIONS
1) Acetone yields diacetone alcohol when treated with Ba(OH)2. It is the addition product.
However, mesityl oxide is formed when acetone is treated with dry HCl due to subsequent dehydration of
initially formed diacetone alcohol.
The mesityl oxide may further condense with another molecule of acetone to give phorone.
2)
Table of contents Arndt Eistert-Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Aldol addition &
condensation Table of contents Arndt Eistert-Exercises >
ARNDT - EISTERT REACTION
* The Arndt-Eistert reaction is employed in converting a carboxylic acid to a higher homologue with
one additional carbon atom.
SOCl2 CH2N2 Ag+
R-COOH -------------> R-COCl --------------> R-COCHN2 ----------------------> R-CH2CONu
ether, Et3N Nucleophile (Nu)
* The following steps are involved in the Arndt-Eistert reaction.
1) Conversion of carboxylic acid to an active compound like acid chloride or an anhydride.
R-COOH + SOCl2 --------> R-COCl + SO2 + HCl
2) Conversion of acid chloride to a diazoketone. A base like Et3N is employed to neutralize HCl liberated in this
step.
R-COCl + CH2N2 --------> R-COCHN2 + HCl
3) The Wolff rearrangement of diazoketone into a ketene and subsequent conversion of it to a higher
carboxylic acid or its derivative by using a nucleophile.
Ag2O, Δ or hν, -N2 Nucleophile (Nu)
R-COCHN2 -------------------------------------> R-CH=C=O --------------------------------> R-CH2CONu
diazoketon
eWolff rearrangement ketene
higher
homologue
* Nucleophile (Nu) = water or alcohol or amines
MECHANISM OF ARNDT-EISTERT REACTION
1) Initially the diazomethane is acylated by the acid chloride to give a diazoketone.
* The HCl liberated in the first step must be neutralized by a suitable base to avoid the formation of
chloromethyl ketone.
2) Thus formed diazoketone is rearranged to a ketene. This is called Wolff-rearrangement.
* Silver salts like PhCO2Ag, Ag2O along with heat or light catalyze the Wolff rearrangement.
* The configuration of 'R' group during Wolff rearrangement is retained.
3) The ketene is immediately attacked by an appropriate nucleophile in the solution.
ILLUSTRATIONS
1) Arndt-Eistert reaction is used in the conversion of 4-nitrobenzoic acid to (4-nitrophenyl)acetic acid as shown
below.
* The nitro group is not affected in the above reaction.
2)
* The carboxylic group is first converted to an anhydride using ethyl chloroformate, ClCO2Et.
* Also note that the configuration at stereogenic carbon is retained.
< Aldol addition &
condensation Table of contents Arndt Eistert-Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Arndt-Eistert part-1 Table of contents Baeyer villiger explanation >
ARNDT - EISTERT REACTION - EXERCISES
I) Carry out the following conversions using appropriate reagents.
II) Write the products formed during the following reaction sequences.
< Arndt-Eistert part-1 Table of contents Baeyer villiger explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Arndt Eistert-Exercises Table of contents Baeyer villiger-Exercises >
BAEYER VILLIGER OXIDATION (REARRANGEMENT)
* The Baeyer villiger oxidation is used to oxidize ketones to esters by using peroxy acids.
Note: The Baeyer villiger rearrangement is a regioselective reaction. In above case, the R' group is assumed to
possess greater migratory aptitude and hence only one product is formed preferentially.
* This reaction involves the oxidative cleavage of C-C bond.
* The reagents which can be employed in Baeyer villiger oxidation include:
Metachloroperbenzoic acid (MCPBA),
Peroxyacetic acid (PAA),
Peroxytrifluoroacetic acid (TFPAA)
Hydrogen peroxide/BF3 ,
Caro's acid buffered with disodium hydrogen phosphate
Sodium percarbonate (Na2CO3.1.5H2O2),
Magnesium salt of monoperoxyphthalic acid (MMPP),
Potassium peroxomonosulphate (potassium caroate) supported on hydrated silica also known as
"reincarnated caro's acid".
Baeyer villiger monooxygenase (an enzyme abbreviated as BVMO).
* Cyclic ketones furnish lactones (cyclic esters).
* The aldehydes may give carboxylic acids or formates. In the latter case, alcohols are finally formed due to
hydrolysis of unstable formates under the reaction conditions.
MECHANISM OF BEAYER VILLIGER OXIDATION
* Initially the peroxy group is added to the carbonyl carbon to give a Criegee like intermediate. Then one of
the group attached to carbonyl carbon is migrated on to the electron deficient oxygen atom in a concerted step,
which is the rate determining step.
* The substituents which can stabilize the positive charge can migrate readily. The migratory aptitude of
various substituents is approximately:
3o-alkyl > cyclohexyl > 2o- alkyl > benzyl > aryl > 1o - alkyl > methyl.
* The electron withdrawing groups (-I groups) on peroxy acids enhance the rate of the reaction.
* Thus the Baeyer villiger oxidation of unsymmetrical ketones is regioselective.
* As the rearrangement is a concerted process, the configuration of the migrating chiral substituent is retained.
* In case of aldehydes, usually the hydrogen atom is migrated preferentially and thus by furnishing carboxylic
acids. But formates are also produced when the migrating group is other than the hydrogen. This is possible when
the other substituent is a tertiary alkyl group or electron rich vinyl or aryl group (e.g. Dakin reaction).
* One of the competing reaction is the formation of epoxide when a double bond is present in the molecule
especially at low temperatures in neutral solvents.
ILLUSTRATIONS
1) In the following Baeyer villiger oxidation, the preferential migration of more substituted secondary alkyl
group is observed (regioselective) without disturbing its chiral integrity i.e., the configuration at the chiral carbon is
retained in the product (stereospecificity).
2) Cyclic ketones furnish lactones as illustrated below.
3) Cyclohexyl group migrates preferentially over methyl group as illustrated below:
4) In the following example, the subsequent hydrolysis of the ester gives the desired alcohol. Another example
of regioselectivity and stereospecificity.
5) Baeyer villiger oxidation is preferred over the epoxidation of double bond by the peracid as illustrated in the
following reaction.
6) The lactone formed can be reduced to a dihydric alcohol.
7) The bacteria strain variants which produce BVMO can be employed in Baeyer villiger oxidation.
8) In the following reaction, the aldehyde is oxidized to formate due to preferential migration of aryl group. But
it undergoes hydrolysis under the reaction conditions to yield a phenol. This reaction is similar to that of Dakin
reaction.
9) As illustrated below, the aldehyde group is oxidized to carboxylic acid due to preferential migration of the
hydride ion. The aryl group with electronegative halogen groups has less migratory aptitude. Remember the groups
which can stabilize positive charge possess greater migratory aptitude.
10) The greater migratory aptitude of aryl group over the -CH2 group can be observed in the following example.
11) The -CH2 group is migrated preferentially in the following reaction. The -CH-CF3 group has less migratory
aptitude due to electron withdrawing nature.
< Arndt Eistert-Exercises Table of contents Baeyer villiger-Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Baeyer villiger: Explanation Table of contents Bamford-Stevens reaction >
BAEYER VILLIGER OXIDATION - EXERCISES
I) Write the products formed in the following reactions.
< Baeyer villiger: Explanation Table of contents Bamford-Stevens reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Baeyer villiger-Exercises Table of contents Beckmann-Explanation >
BAMFORD-STEVENS REACTION
* In the Bamford-Stevens reaction, the tosyl hydrazones (p-Toluenesulfonyl hydrazones) of aliphatic
aldehydes or ketones furnish more substituted alkenes when treated with strong bases like NaOMe, NaH, LiH,
NaNH2 etc.
* The reaction may be performed either in protic solvents like glycols or in aprotic solvents like ethylene glycol
dimethyl ether.
* Both the Bamford-Stevens reaction and the Shapiro reaction afford alkenes from tosyl hydrazones.
* In case of Bamford-Stevens reaction, the more substituted alkene is formed as the thermodynamic product.
* Whereas in Shapiro reaction, the less substituted alkene is formed as the kinetic product. This reaction
employs bases such as alkyllithiums and Grignard reagents.
MECHANISM OF BAMFORD-STEVENS REACTION
* The mechanism involves two steps. Initially, the reaction of tosyl hydrazone with a strong base leads to a
diazo compound, which can be isolated in some cases.
* The diazo compound may follow either one of the two pathways depending on the reaction conditions. In
protic solvents, the reaction proceeds via formation of carbenium ion, whereas in aprotic solvents, the reaction
proceeds via a carbene.
In protic solvents:
* In protic solvents, the diazo compound abstracts a proton from the solvent and thus by forming a diazonium
ion, which subsequently loses dinitrogen to give a carbenium ion. Finally, a mixture of E & Z alkenes is formed from
the carbenium ion through loss of a proton.
* However, carbenium ions can easily undergo a Wagner–Meerwein rearrangement, and hence the
corresponding rearranged alkenes may be formed as side products in protic solvents.
Note: A carbenium ion is a trivalent carbocation. Whereas, the carbocation with five coordinated carbon is
nowadays referred to as a carbonium ion.
In aprotic solvents:
* In aprotic solvents, the diazo compound loses dinitrogen and gives a carbene, which undergoes a faster 1,2-
hydrogen shift to furnish a Z-alkene predominantly.
* The desired alkene is obtained in high yield in aprotic solvents.
ILLUSTRATIONS
1) Bamford-Stevens reaction of tosyl hydrazone of 2-methylcyclohexanone affords more substituted 1-
methylcyclohexane.
Whereas, the Shapiro reaction conditions lead to less substituted 3-methylcyclohexane.
2) The Bamford-Stevens reaction of tosyl hydrazone of cyclopropane carbaldehyde furnishes bicyclobutane: a
special case.
< Baeyer villiger-Exercises Table of contents Beckmann-Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Bamford-Stevens reaction Table of contents Beckmann-Exercises >
BECKMANN REARRANGEMENT
* The Beckmann rearrangement is an acid catalyzed rearrangement of an oxime to an N-substituted amide.
* Conc.H2SO4, HCl, PCl5, PCl3, SOCl2, ZnO, SiO2, PPA (Poly phosphoric acid) etc., are commonly employed in
Beckmann rearrangement.
* Mostly applied for ketoximes.
* Aldoximes are less reactive.
* Cyclic oximes give lactams (cyclic amides).
MECHANISM OF BECKMANN REARRANGEMENT
* Initially the -OH group of the oxime is protonated. Then 1,2 shift of alkyl group (R 1) onto electron deficient
nitrogen and the cleavage of N-O bond occurs simultaneously.
Always the alkyl group which is 'anti' to the -OH group on nitrogen undergoes 1,2 shift which indicates the
concerted nature of the beckmann rearrangement.
Comment: The migration of hydrogen is seldom observed. Hence the N-unsubstituted amides cannot be
obtained by beckmann rearrangement reaction.
ILLUSTRATIONS
1) Industrial conversion of cyclohexanone to caprolactam, which is used in the manufacture of Nylon-6,
involves Beckmann rearrangement.
2) The relative migratory aptitudes of different groups in Beckmann rearrangement is illustrated below.
The 1,2 shift of phenyl group is faster than that of alkyl groups. It is due to formation of phenonium ion. Hence
the anti isomer reacts faster than the syn isomer.
3) An Abnormal Beckmann rearrangement occurs when the migrating group departs from the intermediate
and thus by furnishing a nitrile.
< Bamford-Stevens reaction Table of contents Beckmann-Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Beckmann-Explanation Table of contents Birch reduction-Explanation >
BECKMANN REARRANGEMENT - EXERCISES
I) Mention the products formed in the following reactions.
II) How do you carry out the following conversions?
III) Propose a mechanism for the following reaction.
< Beckmann-Explanation Table of contents Birch reduction-Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Beckmann-Exercises Table of contents Birch reduction-Exercises >
BIRCH REDUCTION
* In Birch reduction, aromatic rings are reduced to 1,4-dienes by alkali metals in liquid ammonia.
* Commercial ammonia often contains iron as impurity. Therefore, it is often necessary to distill the ammonia
before using it in the Birch reduction.
* The reaction is carried out at -33oC (boiling point of ammonia). Co-solvents like Et2O, THF, DME etc., are
added to improve the solubility of organic compounds at this temperature.
MECHANISM OF BIRCH REDUCTION
Comments:
* The alkali metals dissolve in liquid ammonia by forming solvated electrons which are responsible for the
reduction.
* The second protonation is almost always occurs at a site para to the first protonation site.
* Hence in the final step of protonation, thermodynamically less stable but kinetically favored 1,4-diene
is formed predominantly (about 80%). But thermodynamically more stable 1,3-diene(conjugated) is not formed
predominantly since it is not favored kinetically.
* The formation of 1,4-diene in Birch reduction can also be explained by "the principle of least motion", which
states that the reaction that involves the least change in atomic positions or electronic configuration is favored
* Alcohols (EtOH or t-BuOH) are used as protonating agents. They also suppress the formation of amide, NH 2-
ion, which may otherwise isomerize the 1,4-diene to more stable 1,3-diene.
* Under the reaction conditions (below 240 K), the alcohols do not react with the metals.
* Relatively the Birch reductions using Li metal are very faster.
ILLUSTRATIONS
1) Naphthalene can be reduced to 1,4,5,8-tetrahydronaphthalene by using Birch reduction conditions.
Regioselectivity in Birch reduction: The positions of protonation on substituted benzenes depend on the
nature of the group. i.e., whether it is electron withdrawing group (EWG) or electron donating group (EDG).
* EWG: The electron-withdrawing groups promote ipso & para reduction. These groups activate the ring
towards birch reduction. Initially the protonations occurs para to the EWG.
E.g. -COOH, -CONH2, aryl group etc.,
* EDG: The electron-donating groups promote ortho & meta reduction. They deactivate the ring for overall
reduction compared to the EWG.
E.g. -R, -OR, -NR2, -SR, PR2, -CH2OH, -CHO, -C(O)R, CO2R etc.,
The -CHO, -C(O)R, CO2R act as electron donating groups because they are reduced to -CH2O- prior to the
reduction of the ring.
2) In the birch reduction of benzoic acid, the protonation occurs at ipso and para positions relative to -COOH
group on the benzene ring.
comments:
* The reason is electron withdrawing groups stabilise the radical anion at ipso and para positions.
* The carboxylate ion, -COO- formed during the reaction is electron rich and hence cannot be reduced.
* The reduction is also possible even without the presence of alcohol due to strong activation by -COOH group.
3) Protonation occurs at ortho and meta positions of benzene ring incase of anisole and thus by giving more
substituted double bond. It is due to the fact that, electron donating groups stabilise the radical anion at ortho and
meta positions.
* The above product can be hydrolyzed to β,γ-unsaturated ketone in presence of mild acid. However, α,β-
unsaturated ketone is formed due to isomerization in vigorous acid catalytic conditions.
4) The electron donating groups deactivate the ring towards birch reduction. This is exemplified below.
The reduction occurs in the unsubstituted ring of naphthalene.
5) But with aniline derivatives (even though electron donating), the conjugated enamines are formed directly
as the major products (No need of acid catalyst).
6) In case of phenols, the birch reduction is not possible. It is because, phenolic function becomes phenolate
ion under the reaction conditions (basic) and does not react further.
7) The carboxyl groups have a dominating directive influence than other groups.
8) The directive influence of alkoxy groups is greater than that of alkyl groups.
9) The carbanion formed during birch reduction can undergo alkylation.
10) Electron deficient heterocyclic aromatic compounds can also be reduced in Birch reduction.
E.g. Pyridine gives 1,4-dihydropyridine, which can be further hydrolyzed to 1,5-dicarbonyl compound.
11) Nowadays alkali metals encapsulated in nano structured oxides like silica gel are used instead of liquid
ammonia-metal solutions. E.g. sodium in silica gel (Na-SG). In the following example, phenanthrene is reduced to
9,10-dihydrophenanthrene
< Beckmann-Exercises Table of contents Birch reduction-Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Birch reduction part-1 Table of contents Cannizzaro reaction: explanation >
BIRCH REDUCTION - EXERCISES
I) Suggest the products likely to be formed during the birch reduction of the following compounds.
II) Write the products formed in the following reactions.
< Birch reduction part-1 Table of contents Cannizzaro reaction: explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Birch reduction: Exercises Table of contents Clemmensen reduction: Explanation >
Cannizzaro reaction: Introduction
Mechanism
Illustrations & Examples
Crossed Cannizzaro reaction
Intramolecular Cannizzaro reaction
CANNIZZARO REACTION : INTRODUCTION
* The disproportionation reaction of aldehydes without α-hydrogens in presence of a strong base to furnish an
alcohol and a carboxylic acid is called Cannizzaro reaction. One molecule of aldehyde is reduced to the
corresponding alcohol, while a second one is oxidized to the carboxylic acid.
* The applicability of Cannizzaro reaction in organic synthesis is limited as the yield is not more than 50% for
either acid or alcohol formed.
* In case of aldehydes that do have α-hydrogens, the aldol condensation reaction takes place preferentially.
* The α,α,α-Trihalo aldehydes undergo haloform reaction in strongly alkaline medium. E.g. Choral will give
chloroform in presence of an alkali.
MECHANISM OF CANNIZZARO REACTION
* The cannizzaro reaction is initiated by the nucleophilic attack of a hydroxide ion to the carbonyl carbon of an
aldehyde molecule by giving a hydrate anion. This hydrate anion can be deprotonated to give an anion in a strongly
alkaline medium. In this second step, the hydroxide behaves as a base.
* Now a hydride ion, H- is transferred either from the monoanionic species or dianionic species onto the
carbonyl carbon of another aldehyde molecule. The strong electron donating effect of O - groups facilitates the
hydride transfer and drives the reaction further. This is the rate determining step of the reaction.
* Thus one molecule is oxidized to carboxylic acid and the other one is reduced to an alcohol.
* When the reaction is carried out with D2O as solvent, the resulting alcohol does not show carbon bonded
deuterium. It indicates the hydrogen is transferred from the second aldehyde molecule, and not from the solvent.
* The overall order of the reaction is usually 3 or 4.
* The Cannizzaro reaction takes place very slowly when electron-donating groups are present. But the reaction
occurs at faster rates when electron withdrawing groups are present.
ILLUSTRATIONS & EXAMPLES OF CANNIZZARO REACTION
1) Formaldehyde is disproportionated to formic acid and methyl alcohol in strong alkali.
2) Benzaldehyde can be converted to benzoic acid and benzyl alcohol.
3) Furfural gives furoic acid and furfuryl alcohol in presence of strong alkali.
4) Crossed Cannizzaro reaction: When a mixture of formaldehyde and a non enolizable aldehyde is treated
with a strong base, the later is preferentially reduced to alcohol while formaldehyde is oxidized to formic acid. This
variant is known as crossed Cannizzaro reaction.
E.g. Benzyl alcohol and formic acid are obtained when a mixture of benzaldehyde and formaldehyde is treated
with alkali.
The reason may be: the initial nucleophilic addition of hydroxide anion is faster on formaldehyde as there are
no electron donating groups on it.
The preferential oxidation of formaldehyde in crossed Cannizzaro reactions may be utilized in the quantitative
reduction of some aldehydes.
5) α-keto aldehydes can be converted to α-hydroxy carboxylic acids by an intermolecular Cannizzaro reaction.
E.g. Phenylglyoxal undergoes intramolecular cannizzaro reaction by giving Mandelic acid (α-
hydroxyphenylacetic acid or 2-Hydroxy-2-phenylethanoic acid)
6) Phthalaldehyde can undergo intramolecular Cannizzaro reaction by giving (o-hydroxymethyl) benzoic
acid.
< Birch reduction: Exercises Table of contents Clemmensen reduction: Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Cannizzaro reaction: explanation Table of contents Favorskii rearrangement: Explanation
>
CLEMMENSEN REDUCTION : EXPLANATION
* The Clemmensen reduction is used to conveniently reduce the carbonyl compounds, which are stable to
strongly acidic conditions, to alkanes.
* In Clemmensen reduction, the amalgamated zinc in HCl is used as reducing agent.
* The C=O group is converted to CH2 group.
* The Clemmensen reduction is complementary to Wolff-Kishner reduction, which may be used to reduce acid
sensitive compounds.
MECHANISM OF CLEMMENSEN REDUCTION
* The Clemmensen reduction occurs over the surface of zinc catalyst. The probable mechanism is shown
below.
* There is a net flow of electrons from zinc to the carbonyl compound.
* As there is no formation of alcohol during the reaction, this method is not useful to reduce alcohols to
alkanes.
ILLUSTRATIONS
1)
Zn-Hg
CH3CHO + 4(H) -----------------> CH3CH3 + H2O
HCl
2)
3) In the following reaction, along with the reduction of carbonyl group, the -OH group is substituted by the -Cl
group (side reaction). However this side reaction can be avoided by employing Wolff-Kishner method.
4) But the phenol group is not affected in Clemmensen reduction. (Why? Ans: Nucleophilic substitution is not
easy on sp2 carbon of benzene ring!)
< Cannizzaro reaction: explanation Table of contents Favorskii rearrangement: Explanation
>
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Clemmenson reduction: Explanation Table of contents Favorskii exercises >
Note: On this page you can also find quasi-Favorskii rearrangement and Wallach degradation.
FAVORSKII REARRANGEMENT
* The Favorskii rearrangement is the base catalyzed rearrangement of enolizable α-haloketones or
cyclopropanones to carboxylic acids or their derivatives.
The α-haloketones must contain acidic α'-hydrogens.
* In Favorskii rearrangement, the esters are formed if alkoxides are used as bases. Whereas the amides are
formed when amines are used as bases.
* The Favorskii rearrangement of α-halo cyclic ketones results in ring contraction.
MECHANISM OF FAVORSKII REARRANGEMENT
* Initially, the α'-carbon is deprotonated to generate an enolate ion which is followed by intra molecular
nuclophilic substitution to give a cyclopropanone by ring closure.
* Thus formed cylcopropanone undergoes nucleophilic addition by a base at the carbonyl carbon which is
followed by the cleavage of the CO-Cα bond. Usually the cleavage occurs so as to give less substituted and more
stable carbanion.
ILLUSTRATIONS
1) In the following Favorskii rearrangement, 2-Chlorocyclohexanone can be converted into ethyl
cyclopentanecarboxylate by treating with sodium ethoxide. The six membered ring is contracted to the five
membered one.
2) 3-Bromobutan-2-one yields 2-methypropanoic acid as major product when treated with alkali. The ring
opening of cyclopropanone derivative occurs to give less substituted carbanion.
3) The α-haloketones will rearrange to amides when the Favorskii reaction is catalyzed by amines.
4) Synthesis of cubane involves favoroskii rearrangement step as shown below.
5) α,α-dihaloketones or α,α'-dihaloketones rearrange to give α, β-unsaturated carboxylic acid derivatives under
Favorskii conditions. For example, 1,3-Dibromobutan-2-one will give ethyl but-2-enoate when treated with sodium
ethoxide.
6) The rearrangement of α,α'-dihaloketones to α-hydroxycarboxylic acids, followed by oxidative
decarboxylation to the ketones is known as Wallach degradation.
7) The rearrangement of non enolizable α-haloketones in presence of bases is called quasi-Favorskii
rearrangement. The synthesis of powerful pain killer Pethidine (also known as Demerol or Meperidine) makes use
of this rearrangement.
The quasi-Favorskii rearrangement involves no cyclopropanone intermediate and follows a semibenzilic
mechanism as shown below.
< Clemmenson reduction: Explanation Table of contents Favorskii exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Favorskii rearrangement:
Explanation Table of contents Finkelstein reaction >
FAVORSKII REARRANGEMENT - EXERCISES
I) Write the products formed in the following reactions.
< Favorskii rearrangement:
Explanation Table of contents Finkelstein reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Favorskii: exercises Table of contents Fittig reaction >
FINKELSTEIN REACTION
* The Finkelstein reaction involves the exchange of one halogen for another, especially, in primary alkyl
halides. It is used to synthesize one alkyl halide from another.
In the classical version of Finkelstein reaction, a primary alkyl halide, RX is treated with an alkali metal halide,
like NaX' or KX', in excess in acetone. The halogen, X in alkyl halide is replaced by X' through an SN2 mechanism.
Acetone
R-X + NaX' <=========> RX' + 2NaX
Where R = alkyl group; X & X' are different halogens (usually X = Cl or Br, X' = F or I).
* The halide exchange is a reversible reaction. The reaction is driven to completion by taking the advantage of
differential solubility of metal halide salts in acetone solvent.
The solubility of sodium chloride or sodium bromide in acetone is much less than the solubility of sodium
iodide. During the reaction of an alkyl chloride or bromide with sodium iodide in acetone, the formed sodium
chloride or bromide precipitates out from the solution and is thus removed from equilibrium and drives the reaction
to completion.. Hence Finkelstein reaction is usually employed to prepare alkyl iodides which are otherwise difficult
to prepare directly.
* The success of this reaction not only depends on the solubility of the metal halide but also depends on:
i) the nucleophilicity of the attacking halide ion,
ii) the nature of the leaving group,
iii) the stability of carbon-halogen bond in the newly formed alkyl halide and
iv) the reactivity of alky halide.
* The F- is a poor leaving group and forms stable C-F bond. Therefore it is possible to exchange other halogen
groups with fluoride by using KF or AgF or gaseous HF in presence of crown ethers, which is used to improve the
solubility of the metal fluoride. The quaternary ammonium fluorides in aprotic solvents can also be used. Thus
Finkelstein reaction is also used to prepare alkyl fluoride.
* The alkyl bromides are more reactive than corresponding chlorides.
* The allyl, benzyl and α-carbonyl halides are more reactive.
* The secondary, tertiary, vinyl and aryl halides are less reactive in Finkelstein reaction. But the reactivity of
secondary and tertiary halides can be improved by using catalysts like ZnCl2, FeCl3 etc., in solvents like CS2.
* The electron donors on the alkyl halide increase the rate of the reaction, whereas the electron withdrawing
groups tend to decrease the rate.
* In the modified version of Finkelstein reaction, an alcohol is first converted to a tosylate or mesylate and then
treated with a metal halide to get the desired alkyl halide. This reaction works since the tosylate and mesylate are
an excellent leaving groups.
ILLUSTRATIONS
1) In the following Finkelstein reaction, the propyl bromide is converted to propyl iodide.
2) In the following Finkelstein reaction, TetraButyl Ammonium Fluoride (TBAF) is used to prepare
(fluoromethyl)cyclohexane.
3) The halogen exchange for a tertiary halide can be achieved by using ZnCl2 as catalyst in CS2.
4) An alcohol can be converted to a tosylate and then to an alkyl iodide as illustrated in the following scheme
of reactions. The tosylate is formed by reacting the alcohol with Tosyl chloride in presence of Et3N in
dichloromethane. This is a modified version of Finkelstein reaction.
< Favorskii: exercises Table of contents Fittig reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Finkelstein reaction Table of contents Friedel-Crafts alkylation >
FITTIG REACTION
* In Fittig reaction, two aryl halides are coupled in presence of sodium metal in dry ether or tetrahydrofuran to
furnish biaryls.
Dry Ether
Ar-X + 2Na + X-Ar -----------------> Ar-Ar + 2NaX
Where Ar = aryl group, X = halogen
* The yields will be improved by using ultrasound, especially in two-phase reactions.
* A modification of reaction which involves, an alkyl halide and an aryl halide is called Wurtz-Fittig reaction.
* Refer Wurtz reaction for the reaction conditions and the detailed mechanism.
ILLUSTRATIONS
1) Biphenyl can be prepared by Fittig method as follows:
< Finkelstein reaction Table of contents Friedel-Crafts alkylation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Fittig reaction Table of contents Hunsdiecker reaction >
FRIEDEL CRAFTS ALKYLATION
The Friedel-Crafts alkylation involves the electrophilic substitution of alkyl groups on aromatic rings when
arenes are treated with alkyl halides in presence of Lewis acids.
* The alkenes or alcohols can also be used to alkylate aromatic rings under Friedel-Crafts conditions.
* This reaction is catalyzed by Lewis acids like anhydrous AlCl3, FeX3, ZnCl2, BF3 etc.
* It is a reversible reaction and hence dealkylation is also possible under the above said conditions.
* The Friedel-Crafts alkylation fails when the aromatic systems contain more powerful electron withdrawing
groups than halogens (like nitro group).
Aniline does not undergo alkylation since the lone pair on nitrogen of amino group forms coordinate bond with
AlCl3, preventing the complexation to alkyl halides.
* The aryl halides cannot be used to instead of alkyl halides.
MECHANISM OF FRIEDEL CRAFTS ALKYLATION
1) Initially, a complex is formed due to coordination of alkyl halide to the Lewis acid. This complex may act as
the electrophilic reagent or it may dissociate to give a free carbocation, which can act as electrophile.
2) The next step involves the addition of the complex or the carbocation to the aromatic system to give a σ-
complex, which loses a proton subsequently to reconstitute the aromatic system.
* The π electrons on aromatic ring act as nucleophilic system. They attack the electron deficient carbocation
to form the σ-complex.
* The σ-complex formed is also resonance stabilized. However it is not as stable as the initial aromatic system.
* The carbocation may rearrange to give unexpected products.
* The carbocations may also be generated either i) by protonating the alkenes or ii) from alcohols by
dehydration.
* Since the product formed is highly activated towards the electrophilic substitution, further alkylation is also
possible leading to formation of poly alkylated products. This is one of the drawback of this reaction.
ILLUSTRATIONS
1) Toluene is formed when benzene is treated with methyl chloride (chloromethane) in presence of anhydrous
aluminium chloride.
However, toluene is even more reactive than benzene and hence may undergo further substitution to give a
mixture of polymethylated benzenes.
2) Cumene (Isopropylbenzene) is formed as major product when benzene is treated with propyl bromide at
80oC in presence of anhydrous aluminium chloride.
The propyl carbocation is rearranged to more stable isopropyl carbocation by hydrogen ion shift during the
reaction. Hence the major product is cumene rather than propyl benzene.
Note: However if the reaction is carried out at room temperature, the major product is propyl benzene.
3) The alkenes can also be used to generate the electrophilic carbocation. The carbocation is generated by
using a protic acid. The proton is added to the the doubly bonded carbon so as to generate the more stable
carbocation.
E.g. Cumene can also be prepared by the when benzene is treated with propylene gas under 30 atm of
pressure in presence of H3PO4. Again the stable secondary carbocation is generated from the alkene during the
reaction. Sulfuric acid can also be used as catalyst.
4) The alcohols are also used to generate the carbocations which may further participate in Friedel-Crafts
reaction.
E.g. 1,4-dimethoxybenzene reacts with t-butyl alcohol to form 1, 4-Di-t-butyl-2, 5–dimethoxybenzene in
presence of sulfuric acid acting as catalyst. In this reaction, t-butyl carbocation is generated via dehydration of
protonated alcohol.
5) The Friedel-Crafts alkylation is a reversible reaction unlike acylation. Hence a sequence of alkylation and
dealkylation steps are possible through out the reaction. This may sometimes lead to unexpected products under
thermodynamic control conditions such as prolonged reaction times or at high temperatures.
E.g. Toluene undergoes ortho and para substitutions when treated with chloromethane at room temperature to
give ortho and para xylenes. However meta xylene is formed as the major product when the reaction mixture is
heated to 80 oC.
In fact, meta xylene is obtained when either ortho xylene or para xylene is heated with AlCl3/HCl mixture due to
rearrangement which involve dealkylation and alkylation steps.
6) When benzene is made to react with ethyl bromide at room temperature for several hours, the final major
product formed is thermodynamically more stable 1,3,5-triethylbenzene. The meta substitutions occur due to less
steric interactions.
The initially formed mono substituted product directs the orientation for second ethyl group at ortho and para
positions. However these kinetically favored but thermodynamically less stable products may undergo dealkylation
and prefer to take the meta position during the prolonged hours of the reaction.
7) Durene (1,2,4,5-tetramethyl benzene) is obtained as major product when para xylene is reacted with
chloromethane under Friedel-Crafts conditions.
The pentamethyl and hexamethyl benzenes are also formed as side products.
8) Diphenylmethane is obtained when an excess of benzene is reacted with dichloromethane in presence of
AlCl3. The two chlorine atoms of dichloromehtane (methylene chloride) are replaced by benzene rings.
The same product is obtained when benzene is treated with benzene under Friedel-Crafts conditions.
9) Triphenylmethane can be prepared by reacting excess of benzene with trichloromethane (chloroform) in
presence of anhydrous aluminium chloride.
10) However Triphenyl chloromethane (Tritylchloride) is obtained when excess of benzene reacts with
tetrachloromethane (carbon tetrachloride) under Friedel-Crafts conditions. The replacement of fourth halogen atom
is not possible due to steric hindrance.
11) The formation of tetralin in following reaction involves intramolecular Friedel-Crafts reaction.
< Fittig reaction Table of contents Hunsdiecker reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Friedel-Crafts alkylation Table of contents Mannich reaction: Explanation >
HUNSDIECKER REACTION
The decarboxylation of silver salts of carboxylic acids to alkyl bromides by treating with bromine is known as
Hunsdiecker reaction. The alkyl bromide contains one carbon less than those in carboxylic acid.
This reaction is also known as Borodin-Hunsdiecker reaction.
* Very good yields are obtained with alkyl groups containing 2 to 18 carbons. This reaction works with linear as
well as branched chains. However the reaction is seldom works with alkyl groups containing unsaturation.
* This reaction is usually carried out in carbon tetrachloride solvent.
* Although bromine is used often, the reaction is also possible with chlorine and iodine.
* When iodine is used, the ratio between the silver carboxylate and iodine is very important and determines
the products.
A 1:1 ratio of silver salt and iodine gives the alkyl halide.
However, an ester, RCOOR is formed when the reaction is carried out with a 2:1 ratio of silver carboxylate and
iodine. This is called as Simonini reaction.
* Incase of aromatic carboxylates, the Hunsdiecker reaction is possible when the aromatic ring contains
electron-withdrawing groups.
Otherwise, if the aromatic system contains electron-donating groups, the bromine will substitute one of the
hydrogen on the aromatic ring rather than promoting the Hunsdiecker reaction.
However the use of NBS instead of bromine will give the desired Hunsdiecker product. This reagent is
especially useful since it produces bromine free radicals slowly.
* The silver carboxylate used as the starting material must be sufficiently pure and dry. It can be prepared
from the corresponding carboxylic acid by treating it with silver oxide, Ag2O.
Christol-Firth Modification: It is possible to perform the Hunsdiecker reaction conveniently on the free
carboxylic acid instead of the silver salt, which otherwise requires purification. In this modification the free
carboxylic acid is treated with a mixture of mercuric oxide, HgO and bromine in CCl 4. There is no need to isolate an
intermediate salt.
MECHANISM OF HUNSDIECKER REACTION
Initiation: Initially the bromine reacts with the silver carboxylate to give an unstable acyl hypobromite. The
driving force of this step is the precipitation of the extremely poorly soluble and stable AgBr.
The acyl hypobromite decomposes by homolytic cleavage of relatively weak O-Br bond to furnish an acyl free
radical.
Propagation: The acyl free radical undergoes decarboxylation to furnish an alkyl free radical, which reacts
with acyl hypobromite to give the final product alkyl bromide along with the formation of a new acyl free radical.
The following facts support the above proposed free radical mechanism for Hunsdiecker reaction.
i) No rearrangement of alkyl groups
ii) The formation of side products like R-R.
iii) If the alkyl group, R is chiral, it loses its optical activity during this reaction.
ILLUSTRATIONS
1) The silver salt of propionic acid is converted to ethyl bromide when treated with bromine in
tetrachloromethane.
2) In the following reaction, the use of NBS (N-Bromosuccinimide) reduces the chances of electrophilic
substitution on benzene ring.
3) The Christol-Firth Modification is used in the preparation of [1.1.1]propellane (tricyclo[1.1.1.01,3]pentane).
The conversion of Bicyclo[1.1.1]pentane-1,3-dicarboxylic acid to the corresponding dibromide is achieved by using
mercuric oxide and bromine in carbon tetrachloride as shown below.
< Friedel-Crafts alkylation Table of contents Mannich reaction: Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Hunsdiecker reaction Table of contents Michael addition : Explanation >
MANNICH REACTION
The Mannich reaction is the aminoalkylation reaction, involving the condensation of an enolizable carbonyl
compound (α-CH acidic compound) with a nonenolizable aldehyde (like formaldehyde) and ammonia; or a primary
or a secondary amine to furnish a β-aminocarbonyl compound, also known as Mannich base.
* Instead of formaldehyde, other aliphatic or aromatic aldehydes or ketones can be employed.
* The amine used may be ammonia or 1o or 2o aliphatic amine. Mostly dimethyl amine is used. The aromatic
amines do not undergo Mannish reaction.
The reaction is usually carried out with the hydrochloride salt of amine. This salt exists in equilibrium with the
free amine and proton. Hence the acidic conditions are maintained in Mannich reaction.
The Eschenmoser's salt, [(CH3)2N=CH2]+I- is used as a source of formaldehyde and dimethyl amine for
Mannich reactions.
* The α-CH acidic compounds include carbonyl compounds, nitriles, aliphatic nitro compounds, alkynes, α-alkyl-
pyridines or imines, activated phenyl groups and electron-rich heterocycles such as furan, pyrrole, thiophene,
Indole etc.
* The reactions are usually carried out in aqueous or alcoholic solutions.
* Since the β-aminocarbonyl compounds can be conveniently reduced to β-aminoalcohols, which show
considerable pharmacological activity, the Mannich reaction plays an important role in pharmaceutical chemistry.
MECHANISM OF MANNICH REACTION
* Initially an iminium ion is formed due to nucleophilic addition of amine to formaldehyde and subsequent loss
of water molecule.
* Since the reaction is carried out in acidic conditions, the enolizable carbonyl compound is converted to enol
form, which attacks the iminium ion at positively charged carbon adjacent to nitrogen to give finally a β-
aminocarbonyl compound.
ILLUSTRATIONS & APPLICATIONS OF MANNICH REACTION
1) 4-(dimethylamino)butan-2-one is obtained when acetone reacts with formaldehyde and dimethylaminium
chloride.
2) The Mannich reaction of acetophenone with formaldehyde and dimethylaminium chloride in alcohol
furnishes the salt of 2-(dimethylamino)-1-phenylethanone, which can be conveniently eliminated to acrylophenone
(1-phenylprop-2-en-1-one), an α,β-unsaturated compound.
3) In the following example of Mannich reaction, the 2-[(dimethylamino)methyl]-6-methylcyclohexanone, a
Mannich base is obtained from the kinetically favored enol form of 2-methylcyclohexanone. Thus formed Mannich
base is methylated to give a quaternary ammonium salt which undergoes elimination easily to give an α,β-
unsaturated compound (2-methyl-6-methylidenecyclohexanone).
4) The Mannich reaction on Pyrrole with dimethyl amine and formaldehyde is shown below. The use of strong
acids is avoided to suppress the unwanted polymerization of pyrrole. Hence acetic acid is used as solvent.
5) Phenol gives a trisubstituted product in the Mannich reaction.
6) Ethylmalonic acid also undergoes aminomethylation at active -CH site as shown below.
7) Phenylacetylene readily reacts with formaldehyde and dimethylamine to give the following Mannich base.
8) The Robinson-Schopf synthesis of Tropinone involves Mannich reaction. The succindialdehyde
(butanedial) is treated with methylamine and 3-oxoglutaric acid (3-oxopentanedioic acid) to get Tropinone.
9)
< Hunsdiecker reaction Table of contents Michael addition : Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Mannich reaction Table of contents Michael addition : Exercises >
MICHAEL ADDITION : EXPLANATION
* The Michael reaction is the conjugate 1,4-addition of a resonance stabilized carbanion (michael donor) to an
activated α,β-unsaturated compound (michael acceptor).
Michael donors:
The Michael donors contain active -CH2 (methylene) group or -CH group. The acidic nature of methylene group
is enhanced by the electron withdrawing groups (EWG) like: keto, cyano, nitro, carboxylic acid derivatice etc.
E.g. Active methylene compounds like Malonates (e.g.Diethyl malonate), β-keto esters (e.g.Acetoacetic ester)
etc., are some of the examples for Michael donors.
Michael acceptors:
Not only α,β-unsaturated ketones, however, and also esters; nitriles; sulfones; and compounds with activated
double bonds can act as Michael acceptors. Vinyl ketones, alkyl acrylates, acrylo nitrile, fumarates etc., are some
examples.
* A strong base is employed to generate enolate ion from Michael donor. The bases used in the reaction
include: alkoxides, LDA, NaOH, KOH etc., in protic solvents like alcohols.
* Michael addition is a thermodynamically controlled conjugate 1,4 addition reaction and competes with
kinetically controlled 1,2 addition to C=O. At low temperatures, 1,2 additon occurs predominantly. But at higher
temperatures, the michael addition is the preferred route.
MECHANISM
* Initially a resonance stabilized enolate ion (nucleophile) is produced from Michael donor in presence of a
strong base.
It is added to the 4th carbon of α,β-unsaturated carbonyl compound and thus by giving a new enolate, which
usually yields the final compound upon hydrolytic workup.
Note: The final product formed in protic workup appears to be a 3,4-addition product.
* The conjugate 1,4-addition product is thermodynamically controlled and occurs predominantly at relatively
higher temperatures. But a kinetically controlled 1,2-addition is also possible which is preferred at low temperatures
as shown below.
ILLUSTRATIONS
1) Michael addition of diethyl malonate with methyl vinyl ketone followed by protic workup yields a 1,5-
dicarbonyl compound.
Note: Hydrolysis of ester groups and decarboxylation occurs in the final step.
2) Ethyl acetoacetate (acetoacetic ester) can be used as michael donor.
3) In the following reaction, Michael addition of diethyl malonate to mesityl oxide yields a 5-Oxocarboxylic
acid.
4) Usually more substituted alpha-carbon of Michael donor is involved in the addition.
5) Robinson annulation involves, the Michael addition followed by intramolecular aldol condensation as
illustrated below.
6) Both cis and trans isomers are possible in Michael addition involving alkynes.
7) Michael additions to extended conjugate systems is also observed. Following is an example of 1,6-addition.
8) Nitroalkanes with α-hydrogens are excellent Michael donors. The Michael addition of nitromethane with
acrylonitrile is one such example. In this case, three moles of acrylonitrile are involved in the addition.
9) Enamines are excellent Michael donors. These are usually generated by treating carbonyl compounds with
pyrrolidine. The reaction of enamines with michael acceptors is also known as Stork-Enamine reaction.
10) Bicyclo[2.2.2]octane systems can be prepared by double michael addition as illustrated below.
< Mannich reaction Table of contents Michael addition : Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Michael addition: explanation Table of contents Phillips condensation >
MICHAEL ADDTION REACTION - EXERCISES
I) Suggest the addition products likely to be formed between the following Michael donor and Michael
acceptor under the thermodynamic conditions.
< Michael addition: explanation Table of contents Phillips condensation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Michael addition: Exercises Table of contents Reformatsky : Explanation >
PHILLIPS CONDENSATION REACTION : EXPLANATION
* The Phillips reaction involves the condensation of ortho phenylenediamines with organic acids in presence of
dilute mineral acids to furnish benzimidazoles.
* This method has the advantage that the benzimidazoles, which cannot be prepared by heating the
components together, are obtained easily by using dilute acids at lower temperatures.
* Good yields are obtained with aliphatic acids.
* However the yield can be improved by carrying out the Phillips reaction in sealed tubes with aromatic acids
also.
MECHANISM OF PHILLIPS REACTION
* Initially one of the amine group is acylated with the organic acid in presence of mineral acid to furnish an N-
acylated compound. In the next step, the other nitrogen is also acylated by making bond with the carbonyl carbon
of the first acyl group leading to ring closure.
ILLUSTRATIONS OF PHILLIPS REACTION
1) Benzene-1,2-diamine can be condensed with acetic acid in presence of 4N HCl to give 2-methyl-1H-
benzimidazole.
2) 2-phenyl-1H-benzimidazole can be prepared by carrying out the Phillips reaction in a sealed tube at 180oC
< Michael addition: Exercises Table of contents Reformatsky : Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Phillips condensation Table of contents Reformatsky : Exercises >
REFORMATSKY REACTION : EXPLANATION
* The Reformatsky reaction involves the treatment of an α-halo ester with zinc metal and subsequent
reaction with aldehyde/ketone to get β- hydroxy ester.
* Usually inert solvents like diethyl ether or THF are used in Reformatsky reaction.
* Better yields are obtained by using Zn-Cu couple or in situ preparation of zinc by reduction of zinc halides by
potassium (also known as Rieke zinc).
MECHANISM OF REFORMATSKY REACTION
* Initially zinc reacts with α-halo ester to give an organozinc reagent called reformatsky enolate. It is just like
the Grignard reagent. It is added to the carbonyl group of aldehyde or ketone to furnish β- hydroxy ester.
* The organozinc reagents are less reactive and hence the nucleophilic addition to the ester group seldom
occurs. Some of them are quite enough stable to be isolated and can be elucidated for the structure by techniques
like X-ray analysis.
ILLUSTRATIONS
1) The following reaction is a classical example of Reformatsky reaction.
Zn H3O+
CH3CHO + Br-CH2-COOC2H5 -----------------> -----------> CH3CH(OH)-CH2COOC2H5
Diethyl ether
2) The Reformatsky reaction is involved in the formation of following β- hydroxy ester, which upon
condensation gives Coumarin as the final product.
< Phillips condensation Table of contents Reformatsky : Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Reformatsky: Explanation Table of contents Swern oxidation >
REFORMATSKY REACTION : EXERCISES
I) Write the product(s) likely to be formed in the following reactions.
II) How do you carry out the synthesis of following compounds using Reformatsky method?
< Reformatsky: Explanation Table of contents Swern oxidation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Reformatsky reaction: Exercises Table of contents Williamson's syntheis: Explanation >
SWERN OXIDATION
In Swern oxidation, the primary or secondary alcohols are oxidized to aldehydes or ketones respectively by
treating them with dimethyl sulfoxide (DMSO) activated by oxalyl chloride at low temperatures (-78 oC to -60 oC)
and then with an organic base like triethyl amine.
* Further oxidation of aldehydes to carboxylic acids is not possible under swern oxidation conditions.
* The Swern oxidation is the best alternative to the use of carcinogenic chromium based oxidizing agents.
* The reaction must be performed below -60 oC to avoid the formation of side products like mixed thioacetals.
However the use of trifluoro aceticanhydride instead of oxalyl chloride, (COCl)2 allows the reaction to be warmed
upto -30 oC.
* The dimethyl sulfide (DMS) is formed as a byproduct. It has very unpleasant smell. Hence the glassware is
usually rinsed with sodium hypochlorite to oxidize it.
To avoid the not only the formation of volatile and malodorous dimethyl sulfide but also to facilitate the
workup, the alternative sulfoxides like dodecyl methyl sulfoxide or sulfoxides bound to polymers can be used.
MECHANISM OF SWERN OXIDATION
* The DMSO reacts with oxalyl chloride and gets converted to a reactive species, dimethylchlorosulfonium ion.
* The dimethylchlorosulfonium ion, thus formed, reacts with the alcohol to give an alkoxysulfonium ion.
* The deprotonation of the alkoxysulfonium ion using a base furnishes sulfur ylide, which undergoes β-
elimination through a five membered cyclic transition state to give a carbonyl compound and dimethyl sulfide.
ILLUSTRATIONS
1) The hexan-1-ol is conveniently oxidized to hexanal in Swern oxidation.
2) The oxidation of alcohols occurs selectively in presence of disulfide in Swern conditions. The sulfurs are not
oxidized.
3) In some cases, the side reactions like α-epimerization and migration of double bonds into conjugation with
newly formed carbonyl group are possible with the use of triethylamine as the base. To mitigate these reactions, a
bulkier base like diisopropylethylamine (iPr2NEt) also known as, Hünig's base can be employed.
E.g.
However the double bond can be migrated when triethylamine is used.
4) Some times the use of N-ethylpiperidine as a base may improve the yields in Swern oxidation.
< Reformatsky reaction: Exercises Table of contents Williamson's syntheis: Explanation >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Swern oxidation Table of contents Williamson's syntheis: Exercises >
WILLIAMSON'S SYNTHESIS
* In Williamson's synthesis, an ether is prepared by the nucleophilic substitution (typically SN2) of organic
halide with an alkoxide ion.
R-O- + R'-X -----------------> R-O-R' + X-
Alkoxid
e
ion
Halid
e Ether
* The alkoxide ion is generated in situ by treating an alcohol with a metal or a strong base.
* Williamson's synthesis follows bimolecular nucleophilic substitution (SN2) pathway.
* Both symmetrical or unsymmetrical ethers can be prepared.
* In Williamson's synthesis, the nature of alkoxide ion is less important. It may be primary or secondary or
tertiary.
* But due to strongly alkaline conditions, dehydrohalogenation (elimination) is a side reaction. Hence the yields
are relatively better with methyl or primary alkyl halides only.
The yields are affected when halides contain β-hydrogen. Elimination products are formed exclusively with tert-
halides.
MECHANISM OF WILLIAMSON'S SYNTHESIS
* It is a typical SN2 reaction. The alkoxide ion attacks the carbon atom containing the halogen atom from the
back side. The bond making and breaking occurs simultaneously in the transition state.
ILLUSTRATIONS
1) A classical example of Williamson's synthesis can be seen in the preparation of diethyl ether as shown
below. Note that, initially, the sodium ethoxide is generated by treating ethyl alcohol with sodium metal.
Na C2H5Cl
C2H5OH --------------> C2H5O-Na+ ------------------> C2H5OC2H5
-NaCl
2) A cyclic ether is formed in the following reaction.
3) In the following Williamson's synthesis, propene is also formed in good quantities due to elimination side
reaction.
4) An epoxide can be synthesized from a halohydrin using Williamson's reaction.
5) Phenoxide ions can be employed to get aromatic ethers.
Note: Halobenzenes do undergo nucleophilic substitution and hence they cannot be not used in Williamson's
synthesis.
< Swern oxidation Table of contents Williamson's syntheis: Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Swern oxidation Table of contents Williamson's syntheis: Exercises >
WILLIAMSON'S SYNTHESIS
* In Williamson's synthesis, an ether is prepared by the nucleophilic substitution (typically SN2) of organic
halide with an alkoxide ion.
R-O- + R'-X -----------------> R-O-R' + X-
Alkoxid
e
ion
Halid
e Ether
* The alkoxide ion is generated in situ by treating an alcohol with a metal or a strong base.
* Williamson's synthesis follows bimolecular nucleophilic substitution (SN2) pathway.
* Both symmetrical or unsymmetrical ethers can be prepared.
* In Williamson's synthesis, the nature of alkoxide ion is less important. It may be primary or secondary or
tertiary.
* But due to strongly alkaline conditions, dehydrohalogenation (elimination) is a side reaction. Hence the yields
are relatively better with methyl or primary alkyl halides only.
The yields are affected when halides contain β-hydrogen. Elimination products are formed exclusively with tert-
halides.
MECHANISM OF WILLIAMSON'S SYNTHESIS
* It is a typical SN2 reaction. The alkoxide ion attacks the carbon atom containing the halogen atom from the
back side. The bond making and breaking occurs simultaneously in the transition state.
ILLUSTRATIONS
1) A classical example of Williamson's synthesis can be seen in the preparation of diethyl ether as shown
below. Note that, initially, the sodium ethoxide is generated by treating ethyl alcohol with sodium metal.
Na C2H5Cl
C2H5OH --------------> C2H5O-Na+ ------------------> C2H5OC2H5
-NaCl
2) A cyclic ether is formed in the following reaction.
3) In the following Williamson's synthesis, propene is also formed in good quantities due to elimination side
reaction.
4) An epoxide can be synthesized from a halohydrin using Williamson's reaction.
5) Phenoxide ions can be employed to get aromatic ethers.
Note: Halobenzenes do undergo nucleophilic substitution and hence they cannot be not used in Williamson's
synthesis.
< Swern oxidation Table of contents Williamson's syntheis: Exercises >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Williamson's synthesis: Explanation Table of contents Wittig reaction: Explanation>
WILLIAMSON'S SYNTHESIS: EXERCISES
I) How do you get following ethers using Williamson's synthesis. Write the starting materials and also
mention any side products formed.
< Williamson's synthesis: Explanation Table of contents Wittig reaction: Explanation>
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Williamson's synthesis: Exercises Table of contents Wolff-Kishner reduction >
WITTIG REACTION
The reaction of an aldehyde or ketone with a phosphonium ylide to an alkene and a phosphine oxide is known
as Wittig reaction or Wittig Olefination reaction.
This reaction was discovered in 1954 by Georg Wittig, for which he was awarded the Nobel Prize in Chemistry
in 1979.
* The yields of di- and tri-substituted alkenes from aldehydes and ketones are very high but yields of tetra-
substituted alkenes from ketones are often poor because of steric effects.
PHOSPHONIUM YLIDES (WITTIG REAGENTS)
* The phosphonium ylides or alkylidene phosphoranes, also known as Wittig reagents, can be prepared by
treating tri-substituted phosphines with the alkyl halide to give phosphonium salts, which furnish the ylides upon
treatment with the base.
The suitable bases include NaH, NaOMe, NEt3, BuLi etc.,
The ylides are resonance stabilized structures and usually colored intensely. One of the contributing structure
is a zwitter ionic form with positive and negative charges on adjacent atoms. These are prepared in solutions and
are not generally isolated. Hence usually the ylide is generated in situ during the Wittig reaction.
The ylides are of two types based on their relative stability.
i) Non-stabilized ylides: The ylides with electron donating groups on negatively charged carbon are less
stable and react faster. They also react with dioxygen. Hence the Wittig reaction with non-stabilized ylides is
performed under inert atmosphere.
ii) Stabilized ylides: The ylides with electron withdrawing groups adjacent to the negatively charged carbon
are more stable. These are usually stabilized by conjugation.
* It is generally observed that the geometry of the final alkene depends on the stability of the ylide.
* The unstabilized ylides react faster and lead to (Z)-alkenes.
* The stabilized ylides react slowly and lead to (E)-alkenes.
MECHANISM OF WITTIG REACTION
The mechanism of Wittig reaction is not fully established. However a simplified picture is given below. The
initial step is the nucleophilic addition of negatively charged carbon of ylide onto the carbonyl carbon to give a
betaine, which can cyclize to give an oxaphosphetane as an intermediate. The oxaphosphetane is decomposed to
give an alkene and a phosphine oxide.
The driving force of the Wittig reaction is the formation of highly stable double bond between phosphorus and
oxygen in phosphine oxide. The last step involves the elimination of phosphorus and oxygen through a syn-
periplanar transition state. Hence this step is stereospecific.
Though the formation of betaine is not established, the formation of the four membered oxaphosphetane
intermediate is confirmed by 31P-NMR experiments. Hence now it is believed that the initial addition is concerted to
give the oxaphosphetane directly.
Stereochemical perspective: Both syn and anti diastereomeric oxaphosphetanes are possible. However the
formation of oxaphosphetane is stereoselective depending on the conditions.
With unstabilized ylides: The Wittig reaction with unstabilized ylides yields Z-alkenes predominantly (Z-
selective). This selectivity can be explained as follows:
The carbonyl compound and the ylide approach each other at right angles and form the puckered four
membered oxaphosphetane ring in the transition state, in one step. The transition state is formed such that the
large substituents are kept away from each other leading to the formation of a syn-oxaphosphetane which is less
stable but formed very quickly than the corresponding anti diastereomer. Hence finally the kinetically controlled
Z-alkene is formed.
With stabilized ylides: The Wittig reaction with stabilized ylides is E-selective. Since the ylide is stable and
the formation of oxaphosphetane from the starting compounds is reversible, an equilibration is possible between
relatively less stable syn form and more stable anti form of oxaphosphetane. There is now much time for the syn
oxaphosphetane to interconvert to more stable anti form before the decomposition occurs. Hence the E-alkene
predominates. Thus the selectivity of the final product is thermodynamically controlled.
The Schlosser modification: It is possible to get E-alkenes from non-stabilized ylides using this method
(Wittig-Schlosser reaction).
In Schlosser modification, the initially formed less stable syn betaine can be converted to anti form by treating
with phenyllithium or n-butyllithium at very low temperatures (-78 oC). The treatment of the oxaphosphetane with
these bases results in deprotonation at carbon adjacent to the phosphorus and give a more stable anti form of β-
oxido phosphonium ylide. This will furnish E-alkene finally upon protonation with an acid.
Horner–Wadsworth–Emmons reaction: This is modified Wittig reaction in which carbanions generated from
phosphonate esters are used instead of phosphonium ylides. This reaction is more superior to Wittig reaction since
the carbanion generated from phosponates is more nucleophilic and the phosphate byproducts are water soluble
and can be removed easily. It often gives better yields.
Horner–Wadsworth–Emmons reaction is also known as: Horner–Emmons or Wadsworth– Emmons or Horner–
Wittig reaction.
ILLUSTRATIONS
1) In the following Wittig reaction, the cyclohexanone is converted to methylidenecyclohexane by treating with
(methylene)triphenylphosphorane, which in turn is generated in situ by treating the triphenylphosphine with
methylbromide in presence of a base.
2) In the following example, the Wittig reagent is derived from the α-haloethers. They react with aldehydes or
ketones to form vinyl ethers, which upon subsequent hydrolysis yield aldehydes containing one more carbon atom.
Thus the conversion of cyclohexanone to cyclohexane carbaldehyde is achieved.
3) An exocyclic double bond can be successfully introduced on camphor by treating it with
methyltriphenylphosphonium bromide in presence of potassium tert-butoxide.
4) The Wittig reaction of propanal with butyltriphenylphosphonium iodide, a non-stabilized ylide yields (3Z)-
hept-3-ene selectively.
Note: Above Wittig reagent is non-stabilized since the butyl group is electron donating group.
5) But the E-selectivity is observed in the following Schlosser modification.
6) Whereas E-alkenes are formed predominantly with stabilized ylides as shown in the following Wittig reaction.
< Williamson's synthesis: Exercises Table of contents Wolff-Kishner reduction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
<Wittig reaction: Explanation Table of contents Wurtz reaction >
WOLFF KISHNER REDUCTION
* In Wolff-Kishner reduction, the carbonyl compounds which are stable to strongly basic conditions can be
reduced conveniently to alkanes. The C=O group is converted to CH2 group.
The carbonyl compound is first treated with excess of hydrazine to get the corresponding hydrazone which
upon heating, in presence of a base, furnishes the hydrocarbon.
A high-boiling hydroxylic solvent, such as diethylene glycol (DEG), is commonly used to achieve the
temperatures needed.
* The Wolff-Kishner reduction is complementary to Clemmensen reduction, which is used to reduce base
sensitive compounds.
MECHANISM OF WOLFF KISHNER REDUCTION
ILLUSTRATIONS
1) The Wolff-Kishner reduction of acetone gives propane.
2) The cyclohexane is formed upon Wolff-Kishner reduction of cyclohexanone.
3) The Wolff-Kishner reduction is best suited for the reduction of carbonyl compounds containing groups stable
to strongly basic conditions. In the following example, the alcohol group is not affected during the reduction.
4) However, the base sensitive groups may be affected during Wolff-Kishner reduction. In the following case,
the halogen group undergoes dehydrohalogenation under strongly basic conditions.
This side reaction can be avoided by using Clemmensen reduction.
<Wittig reaction: Explanation Table of contents Wurtz reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Wolff-Kishner reduction Table of contents Wurtz-Fittig reaction >
WURTZ REACTION
* In Wurtz reaction, two alkyl halide molecules are coupled in presence of sodium metal in anhydrous ether or
Tetrahydrofuran to form a new carbon carbon bond and thus by giving a symmetrical alkane.
Dry Ether
R-X + 2Na + X-R -----------------> R-R + 2NaX
Where X = halogen
* The Wurtz reaction must be performed under anhydrous conditions because the alkyl free radical formed (see
the mechanism) during the reaction is strongly basic and can abstract proton from water.
* In case of alkyl and aryl fluorides as well as aryl chlorides, tetrahydrofuran is used as solvent instead of
ether.
* The Wurtz reaction is limited to synthesis of symmetrical alkanes with even number of carbon atoms only.
The number of carbons in the alkane is double that of alkyl halide (n ---> 2n type reaction)
* If dissimilar alky halides are used, a mixture of alkanes is formed. It is usually difficult to separate the mixture
and hence wurtz reaction not a suitable method to synthesize unsymmetrical alkanes.
E.g. The Wurtz reaction between R-X and R'-X yields not only R-R' but also R-R and R'-R'. This mixture cannot
be separated easily.
* Methane cannot be prepared by this method.
* A modification of this reaction involving alkyl and aryl halides is called Wurtz-Fittig reaction. If only aryl
halides are subjected to coupling, the reaction is called as Fittig reaction.
MECHANISM OF WURTZ REACTION
* Initially an alkyl free radical is formed due to transfer of one electron from sodium atom.
R-X + Na ---------> R. + X-
Alkyl free
radical
* In the next step, one more electron is transferred from second sodium atom to the free radical to give a
carbonium ion.
R. + Na ---------> R-Na+
* Thus formed alkyl anion displaces halide ion from the second molecule of alkyl halide. It is an SN2 reaction.
R- Na+ + R-X ---------> R-R + Na+X-
Symmetrical Alkane
Comment: Since the alkyl free radicals are formed, elimination side reactions leading to alkenes is also
possible, especially with bulky alkyl groups, which require more activation energy during the nucleophilic
substitution (SN2) step.
ILLUSTRATIONS
1) Ethane is formed when methyl chloride is treated with sodium metal in dry ether.
Dry Ether
CH3-Cl + 2Na + Cl-CH3 -----------------> CH3-CH3 + 2NaCl
2) Strained carbon skeletons like bicyclobutane ( bicyclo[1.1.0]butane ) can be prepared by an intramolecular
Wurtz reaction as shown below.
3) When tert-butylhalides are subjected to Wurtz reaction, isobutylene is formed as the major product. It is
because the elimination is favored over SN2 mechanism. The SN2 step requires more activation energy due to steric
hindrance.
< Wolff-Kishner reduction Table of contents Wurtz-Fittig reaction >
AdiChemistry Home
NAMED ORGANIC REACTIONS
< Wurtz reaction: Explanation Table of contents
WURTZ-FITTIG REACTION
* The Wurtz-Fittig reaction is the modification of Wurtz reaction. It involves the coupling of an aryl halide with
an alkyl halide molecule in presence of sodium metal to furnish alkylated aromatic hydrocarbons.
Dry Ether
Ar-X + 2Na + X-R -----------------> Ar-R + 2NaX
Where Ar = Aryl group, R = alkyl group, X = halogen
* The more reactive alkyl halide will form the organosodium initially, which acts as a nucleophile and attacks
the aryl halide.
* Usually the yields are very high.
* Refer Wurtz reaction for the reaction conditions and the detailed mechanism.
ILLUSTRATIONS
1) Toluene can be prepared by Wurtz-Fittig method as follows:
< Wurtz reaction: Explanation Table of contents
AdiChemistry Home
PHYSICAL CHEMISTRY HOME PAGE
Physical chemistry deals with the basic principles of physical science involved in chemical systems. It often
deals with the macroscopic side of chemical systems; like inter molecular forces, thermodynamic properties,
chemical equilibria, reaction kinetics and electrochemical processes.
However modern physical chemistry also deals with the principles of quantum mechanics to help in
understanding the chemical phenomena at atomic and molecular level.
On this page you can find links to topics in physical chemistry. You may navigate through the physical
chemistry topics given below.
PHYSICAL CHEMISTRY
TABLE OF CONTENTS
Chemical equilibrium
Chemical kinetics
Electrochemistry
Surface chemistry
CHEMICAL EQUILIBRIUM
TABLE OF CONTENTS
Introduction to Chemical equilibrium & Reversible reactions
Definition of chemical equilibrium
Law of Mass Action
Equilibrium constant (Kc)
Le Chatelier's Principle
CHEMICAL KINETICS
TABLE OF CONTENTS
Introduction to chemical kinetics
Rate of reaction: Definition, Average rate, Instantaneous rate, Units
Kinetic molecular theory or Collision theory of rates of reaction
Factors affecting rate of chemical reaction
Rate law, Order of reaction, Molecularity
ELECTROCHEMISTRY
TABLE OF CONTENTS
Electrochemistry: introduction
Conductivity of electrolytes
Kohlrausch law of independent migration of ions
SURFACE CHEMISTRY
TABLE OF CONTENTS
Introduction to surface chemistry
DISCLAIMER
The chemistry study material available on this site can be used for personal use only. Since the work on this
site is copyrighted and the publication on the web does not imply that this work becomes general property.
You are are welcome to browse and take print-outs of this material and are discouraged to store or copy this
material in electronic form without prior permission of the author.
However teachers are welcome to utilize selected diagrams and material from the site in lecture presentations,
provided the source i.e., http://www.adichemistry.com is appropriately acknowledged.
AdiChemistry Home
Physical chemistry: Home
page Le Chatelier's principle >
CHEMICAL EQUILIBRIUM: INTRODUCTION
Chemical equilibrium deals with extent to which a chemical reaction proceeds.
It is observed that most of the chemical reactions do not go to completion i.e., the reactants are not completely
converted to products. The reaction proceeds to certain extent and reaches a state at which the concentrations of
both reactants and products remain constant with time. This state is generally referred to as equilibrium state.
In these reactions, not only the conversion of reactants to products occurs, but also the conversion of products
to reactants is also possible. These reactions are known as reversible reactions, which reach equilibrium state at
which the number of reactant species converted to products becomes equal to the number of product species
converted to reactants. That is why at equilibrium, there is no observable change in the concentration of reactants
and products. The reaction is said to be halted and no further conversion of reactants is possible under given set of
conditions.
Chemical equilibrium deals with these reversible reactions, which reach equilibrium state. The scope of
chemical equilibrium includes the study of characteristics and factors affecting the chemical equilibria.
IRREVERSIBLE AND REVERSIBLE REACTIONS
Irreversible reaction: A reaction that occur only in one direction is called an irreversible reaction i.e., only
the reactants are converted to products and the conversion of products to reactants is not possible.
The single headed arrow ( ) is used to indicate the irreversible reactions.
E.g.
1) The combustion of methane is an irreversible reaction since it is not possible to convert the products (carbon
dioxide and water) back to the reactants (methane and oxygen).
2) The decomposition of potassium chlorate is also an irreversible reaction. It is not possible to prepare
potassium chlorate directly from KCl and O2.
Reversible reaction : A reaction that occurs in both forward and backward directions is called reversible
reaction. In a reversible reaction, the reactants are converted into products and the products can also be converted
back to the reactants.
The half headed arrows ( ) are used to indicate the irreversible reactions.
E.g. The following reactions are reversible reactions since they occur in both directions.
The chemical equilibrium is possible in reversible reactions only.
CHEMICAL EQUILIBRIUM: DEFINITION
Chemical equilibrium: The state at which the rate of forward reaction becomes equal to the rate of backward
reaction is called chemical equilibrium.
Explanation: Initially the rate of forward reaction is greater than the rate of backward reaction. However
during the course of reaction, the concentration of reactants decreases and the concentration of products
increases. Since the rate of a reaction is directly proportional to the concentration, the rate of forward reaction
decreases with time, whereas the rate of backward reaction increases.
At certain stage, both the rates become equal. From this point onwards, there will be no change in the
concentrations of both reactants and products with time. This state is called as equilibrium state.
The state of chemical equilibrium can be shown graphically as follows:
CHARACTERISTICS OF CHEMICAL EQUILIBRIUM
1) At equilibrium state, the rates of forward and backward reactions are equal.
2) The observable properties such as pressure, concentration, color, density, viscosity etc., of the system
remain unchanged with time.
3) The chemical equilibrium is a dynamic equilibrium, because both the forward and backward reactions
continue to occur even though it appears static externally.
The concentrations of reactants and products do not change with time but their inter conversion continue to
occur.
4) The chemical equilibrium can be reached by starting the reaction either from the reactants side or from the
products side.
5) Both pressure and concentration affect the state of equilibrium but do not affect the equilibrium constant.
6) However, temperature can affect both the state of equilibrium as well as the equilibrium constant.
6) A positive catalyst can increase the rates of both forward and backward reactions and thus helping the
system to attain the equilibrium faster. But it does not affect the state of equilibrium and the equilibrium
constant.
TYPES OF CHEMICAL EQUILIBRIA
The chemical equilibria are classified into two types: 1) Homogeneous equilibrium and 2) Heterogeneous
equilibrium.
1) Homogeneous equilibrium: A chemical equilibrium is said to be homogeneous if all the substances
(reactants and products) at equilibrium are in the same phase.
E.g.
2) Heterogeneous equilibrium: A chemical equilibrium is said to be heterogeneous if all the substances at
equilibrium are not in the same phase.
E.g.
LAW OF MASS ACTION
The law of mass action was proposed by Guld berg and Wage. It can be stated as:
The rate of a reaction at an instant of time is proportional to the product of active masses of the
reactants at that instant of time under given conditions.
The active masses for different substances and systems can be expressed as mentioned below.
i) For dilute solutions, the molar concentrations are taken as active masses.
ii) For gases at low pressures, the partial pressures are taken as active masses. However the molar
concentrations can also be taken as active masses.
iii) The active masses of pure solids and pure liquids are taken as unity since their active masses (or
concentrations) are independent of their quantities taken.
E.g. For the reaction:
N2(g) + 3H2(g) 2NH3(g)
The rate of the reaction at an instant of time can be expressed as:
r ∝ [N2] [H2]3
or
r ∝ pN2.pH23
Where:
[N2] and [H2] are the molar concentrations of gases.
pN2 and pH2 are the partial pressures of gases.
EQUILIBRIUM CONSTANT, Kc (IN TERMS OF MOLAR
CONCENTRATION)
Consider the following reaction at equilibrium;
By applying law of mass action,
The rate of forward reaction can be written as;
Vf ∝ [A]a[B]b
Vf = kf [A]a[B]b
The rate of backward reaction can be written as;
Vb ∝ [C]c[D]d
Vb = kb [C]c[D]d
Where
[A], [B], [C] and [D] are the equilibrium concentrations of A, B, C and D respectively.
a, b, c & d represent the stoichiometric coefficients of A, B, C & D respectively.
Kf and Kb are the rate constants of forward and backward reactions respectively.
However at equilibrium,
rate of forward reaction = rate of backward reaction
i.e. Vf = Vb
Where
Kc is called as equilibrium constant expressed in terms of molar concentrations. It is the ratio of products of
equilibrium concentrations of products to the product of equilibrium concentrations of reactants. In general, it can
be represented as:
Units of Kc: Most of the times the Kc is expressed with out units. However the units of Kc can be given as (mol.L-
1)Δn.
Where Δn = (c+d) - (a+b) = (total no. of moles of products) - (total no. of moles of reactants).
Note: These no. of moles are the stoichiometric coefficients in the balanced chemical equation for the
equilibrium. While counting this number, the no. of moles of solids and liquids are not taken into consideration.
Factors affecting the equilibrium constant:
* There is no effect of pressure, concentration and catalyst on the value of equilibrium constant.
* However, the equilibrium constant depends on the temperature.
Usually, in exothermic reactions, increase in temperature decreases the the equilibrium constant, Kc.
Whereas, in endothermic reactions, increase in temperature increases the Kc value.
EQUILIBRIUM CONSTANT, Kp (IN TERMS OF PARTIAL
PRESSURES)
Kp is the equilibrium constant in terms of partial pressures. Let A, B, C and D are gases in the following
reaction.
Then for the above reaction, the Kp can be written as:
Where PA, PB, PC and PD are the partial pressures of A, B, C and D at equilibrium.
RELATION BETWEEN Kc & Kp
Derivation:
From the ideal gas equation;
Where [M] = molar concentration.
Now we can write: PA = [A]RT, PB = [B]RT, PC = [C]RT & PD = [D]RT
Where Δng = (no. of moles of gaseous products) - (no.of moles of gaseous reactants).
Note: These no. of moles are the stoichiometric coefficients of only gaseous reactants and products in the
balanced chemical equation for the equilibrium.
The following conclusions can be drawn from above equation:
If Δng = 0 then Kp = Kc
If Δng > 0 then Kp > Kc
If Δng < 0 then Kp < Kc
ILLUSTRATIONS
The expressions for Kc and Kp and the relation between them for some reversible reactions are illustrated
below.
Since Δng = (2) - (1+1) = 0
Kp = Kc
Since Δng = (1+1) - (1) = 1
Kp > Kc
Since Δng = (2) - (1+3) = -2
Kp < Kc
Since Δng = (1+3) - (2) = 2
Kp > Kc
i.e., The expressions for Kc and Kp and the relation between them depends on how we expressed the reversible
reaction as the stoichiometric equation.
KC = [CO2]
Since Δng = (1) - (0) = 1
Kp > Kc
In above expressions, the active masses of solids are taken as one and hence do not appear in the expressions.
REACTION QUOTIENTS, Q & QP
The reaction quotient, Q is defined as the ratio of products of concentrations of products to the product of
concentrations of reactants at an instant of time.
i.e., The equilibrium constant, Kc is the special case of reaction quotient, Q.
If the Q value is equal to Kc, the reaction is said to be at equilibrium.
If the Q value is not equal to Kc, the reaction has to be proceeded either to the right (towards the products side)
or to the left (towards the reactants side) to reach the equilibrium state.
For example, if Q < KC, the reactants concentration has to be decreased to make Q equals to KC. Hence the
forward reaction is favored to restore the equilibrium.
Else if, Q > KC, then the products concentration must be decreased to make Q equals to KC again. Hence the
backward reaction is favored to restore the equilibrium.
In the same way, the reaction quotient in terms of partial pressures, Qp can be defined. It is the ratio of product
of partial pressures of products to product of partial pressures of reactants at any instant of time.
The same arguments about Q and Kc are valid for Qp and Kp.
Physical chemistry: Home Le Chatelier's principle >
