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Subject Chemistry

Paper No and Title 5; Organic Chemistry-II

Module No and Title 25; SE1 reactions

Module Tag CHE_P5_M25

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction
3. SE1 reactions
3.1 SE1mechanism
3.2 Stereochemistry of SE1 mechanism

4.Common reactions with SE1 mechanism

5. Summary

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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1. Learning Outcomes
After studying this module, you shall be able to

• Know what are SE1 reactions and mechanisms

• Learn the effect of mechanism on stereochemistry of products
• Identify substrates that would prefer SE1 mechanism
• Analyze the importance of SE1 mechanism in synthetic Chemistry

2. Introduction
The substitution electrophilic unimolecular mechanisms are termed SE1 reactions. These
mechanisms follow first order reaction kinetics with respect to the substrate. The SE1 mechanism
is analogous to the unimolecular mechanisms for nucleophilic substitution (SN1).

3. SE1 reactions

3.1 SE1 mechanism

The SE1 mechanism involves two steps: the first step is a slow rate determining ionization step
leading to formation of the carbanion. The second step involves fast combination of electrophile
resulting in to the products.

3.2 Stereochemistry of SE1 mechanism

The stereochemical outcome of SE1 reactions are difficult to predict owing to the complicated
configuration of carbanions formed during the first step of ionization. The typical carbanion in
theory may have a pyramidal (sp3) or planar (sp2) configuration or may be depending upon the
substituent a configuration in between the two forms. On minimum energy grounds, pyramidal
configurations are favored as the lone pair resides in sp3 orbital.

Fig 1: Flipping of pyramidal carbanions

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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If the carbanion is pyramidal and it can hold its structure, then the product should be with
retention of configuration. Even a pyramidal carbanion has been reported to give racemized
products owning to pyramidal inversion (fig: 1) as is observed with amines (amines; R3N: and
carbanions R3C- are isoelectronic).

If the carbanion has a planar structure than also the attack of electrophile might lead to
racemization of products. Therefore, racemization is almost always observed for the products of
SE1 mechanism (fig 2), although whether this is caused by planar carbanions or by oscillating
pyramidal carbanions in equilibrium is not settled.

c
Fig 2: Mechanism of racemization in SE1 reactions

4. Common reactions involving SE1 mechanism

4.1 Decarboxylation of aliphatic acids

Aliphatic acids with certain functional groups, such as double or triple bonds at or β position
undergo facile decarboxylation. The reaction proceeds via involvement of a carbanion
intermediate that subsequently acquires a proton from the solvent or other source. For such
reactions loss of CO2 is the rate limiting step. Thus the rate law for the following reaction is,

Rate = k[Z-CH2COO-]

Where, Z= COOH, COR, Ar, NO2, CN, CH3

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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Loss of CO2 from di-carboxylic acids such as malonic acid and higher members of the series
occurs readily via SE1 mechanism to give monocarboxylic acids.

4.2 Cleavage of alkoxides

Alkoxide of tertiary alcohols with electron withdrawing substituent may undergo anionic
fragmentation. The reaction proceeds nicely with electron withdrawing aryl, allylic and benzylic
substituents. However, the reaction is unsuccessful when the Z groups are simple unbranched
alkyl groups.

Where Z= COR, Ar, allyl, NO2, CN.

There are reports that the reaction is a simple one step mechanism under gas phase giving the
carbanion and ketone directly.However, with some substrates in solution, the formation of R-R
dimmers have been observed that might point towards a radical mediated mechanism based on
attached substituents.

4.3 Halogenation of ketones

The acid/base catalyzed halogenations of aldehydes/ketones is a classical example of SE1

mechanism.

In unsymmetrical ketones, the preferred site of proton abstraction and halogenation is usually the
more substituted carbon atom. The preferred order for halogenations being CHR2>CH2R>CH3.
Under alkaline conditions one position of a ketone is completely halogenated before the other
position is attacked and generally the reaction cannot be stopped until all the hydrogens of the
first carbon have been replaced with the halogen atom. This is because the electron withdrawing
inductive effect exerted by the halogen makes the -H atoms of the CH2X group more acidic than
CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II
MODULE No: 25 ; TITLE: SE1 reactions
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those of CH3. Therefore the second halogenation is faster than the first and the third halogenations
are faster still.

Haloform reaction is a special case of halogenations of ketones where one of the substituent on
ketone/secondary alcohol is CH3 group. In Haloform reaction in the presence of excess base and
excess of halogen, a methyl ketone is first converted into a trihalo-substituted ketone.

Then hydroxide ion attacks the carbonyl carbon of the trihalo-substituted ketone leading to easy
expulsion of the tetrahedral intermediate, resulting into the final product which is a carboxylic
acid. The reaction is called haloform reaction as one of the products is haloform (chloroform,
bromoform or iodoform). These reactions are common laboratory test for detection of CH3-CO-R
group in an unknown compound.

Example:

4.4 Keto-enol tautomerism

Keto-enol tautomerism is an acid/base catalyzed reversible reaction that occurs in substrates

containing a carbonyl groups attached to a sp3 hybridized carbon bearing one or more hydrogen
atoms. Thermodynamically, the keto isomer is more stable than the enol tautomer.

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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Sometimes intramolecular stabilization through hydrogen bonding or complete electron

delocalization may cause the enol tautomer to be more favored.

4.5 Nitrosation

Compounds with acidic protons such as active methylene group in F3CCOCH2COCF3 can be
nitrosated with nitrous acid or alkyl nitrites. The attacking species is either NO+ or a carrier of it.
The initial product formed is the C-nitroso compound,that is stable only when there is no
hydrogen that can undergo tautomerism. When the substrate is F3CCOCH2COCF3, the
mechanism goes through the enol form as follows;

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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This reaction is often used to prepare amino acids since oximes and nitroso compounds can be
reduced to primary amines.

4.6 Hell- Vohlard-Zelinsky (HVZ) reaction

Carboxylic acids do not undergo substitution reactions at -position under basic conditions
because a base will remove a proton from the -COOH group rather than from -position. If,
however, a carboxylic acid is treated with Br2/PBR3 then the brominated acid can be substituted at
-position. This halogenation reaction is called Hell–Volhard–Zelinsky reaction. The reaction is
named after three chemists, the German chemists Carl Magnus von Hell (1849–1926) and Jacob
Volhard (1834–1910) and the Russian chemist Nikolay Zelinsky (1861–1953).

The proposed mechanism of the reaction is as follows:

In the first step of the HVZ reaction, PBr3 converts the carboxylic acid into an acyl bromide. The
acyl bromide is in equilibrium with its enol form. Bromination of the enol forms leads to alpha
brominated acyl bromide, which is hydrolyzed to the carboxylic acid. This reaction is not
applicable to iodine or fluorine. When there are two a hydrogens, one or both may be replaced,
although it is often hard to stop with just one.

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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4.7 Stork Enamine reaction

In the first step of the reaction from aliphatic ketones enamines are generated. The enamines are
alkylated through a mechanism similar to Friedal Craft’s alkylation.

 
 
Alkylation generally occurs at less substituted side of the original ketone. This method is similar
to aliphatic nucleophilic substitution. The advantage of this reaction is that it can be stopped after
introduction of just one alkyl group.

4.8 Electrophilic substitution accompanied by double bond shift

With allylic substrates the product of electrophilic substitutions generally result in formation of
rearranged products. There are two possible pathways for this reaction. In SE1 pathway the
leaving group is first removed, giving a resonance-stabilized allylic carbanion, which then attacks
the electrophile to give rise to the products.

The reaction proceeds in two steps.

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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~ represents both geometries are possible.

In the first step proton removal leads to formation of carbanion which may rearrange to a better
stable olefin, which then may take up a proton to give rise to rearranged product. Double-bond
rearrangements can also take place on treatment with acids thus both proton and Lewis acids can
be used to catalyze such rearrangement.

Diazo-de-dihydro-bisubstitution

Compounds containing active methylene group (CH2) such as malonic ester can be converted to
diazo compounds on treatment with tosyl azide in the presence of a base.

Where Z and Z’ are = COOR, COR, CHO, CONR2, CN, NO2

This reaction is called the diazo-transfer reaction, which is applicable to other reactive substrates
such cyclopentadiene. The proposed mechanism for the reaction is as follows:

The use of phase-transfer catalysis increases the convenience of the method.

4.9 Aliphatic diazonium coupling reaction

In molecules with active methylene groups (such as diethyl melonate) where the C–H bond is
acidic, in the presence of base, coupling reaction leading to diazonium salts takes place.

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions
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Here Z= COOEt, Aliphatic azo compounds where the carbon containing the azo group is attached
to a hydrogen are unstable and tautomerize to the isomeric hydrazones, which are therefore the
products of the reaction.

5. Summary
• Electrophilic substitution reactions are reactions where an electrophile replaces another
group on the substrate.
• Substitution electrophilic unimolecular reactions are called SE1.
• SE1 reaction follows first order kinetics with respect to the substrate.
• SE1 reactions proceed in two steps; the first one is rate determining proton abstraction
step. The second step is rapid attack of electrophile leading to product formation.
• Owning to the configuration of carbanion intermediate the product of SE1 mechanisms
are generally racemic mixtures.
• Since carbanions are stabilized by electron withdrawing substituents, SE1 reactions are
favored for substrates with –I and –M functional groups.
• SE1 reactions are favored in polar solvents owning to better solvation of carbanions.
• Solvents play a major role in determination of sterochemical outcome of SE1 mechanism.
• A number of synthetically useful name reactions such as Hell-Vohlard-Zelinsky,
Haloform reaction and Stork enamine reaction take up SE1 pathway as an intermediate
step.

CHEMISTRY PAPER No: 5 ; TITLE : Organic Chemistry-II

MODULE No: 25 ; TITLE: SE1 reactions