SUBSTRATE + REAGENT PRODUCTS

Most of the attacking reagents carry either a positive or a negative charge.

The positively charged reagents attack the regions of high electron density in the substrate molecule.

Substrate: The reactant molecule undergoing attack is referred to as the substrate.

Reagent: The general term used to describe the attacking species is the reagent.

The substrate and the reagent interact to yield the products of the reaction.

The carbon bonds in the substrate molecule (organic) are broken (or cleaved) to give fragments which are very reactive and constitute transitory intermediates. At once they may react with other species present in the environment to form new bonds to give the products.

On the other hand, the negatively charged reagent will attack the regions of low electron density in the substrate molecule.

The steps of an organic reaction showing the breaking and making of new bonds of carbon atoms in the substrate leading to the formation of the final products through transitory intermediates, are often referred to as its mechanism.

SUBSTRATE INTERMEDIATE(Transitory)

PRODUCTS

Factors which influence a reactionA reaction may occur or may not occur depending

upon the density of electrons at the site of reaction in the substrate. The factors which influence the electron density in the substrate are :

- Inductive Effect

- Mesomeric Effect

- Electromeric Effect

Inductive effect

The inductive effect (I Effect) refers to the polarity produced in a molecule as a result of higher electronegativity of one atom compared to another.

It involves σ (sigma) electrons. The σ (sigma) electrons which form a covalent bond are seldom shared equally between the two atoms. This is because different atoms have different electronegativity values, i.e. different powers of attracting the electrons in the bond.Consequently, electrons are displaced towards the more electronegative atom. This introduces a certain degree of polarity in the bond. The more electronegative atom acquires a small negative charge (-). The less electronegative atom acquires a small positive charge (+).

Consider the carbon-chlorine bond. As chlorine is more electronegative, it becomes negatively charged with respect to the carbon atom.

Structure I indicates the relative charges on the two atoms. In structure II, the arrow head placed in the middle of the bond indicates the direction in which the electrons are drawn. In structure III, the more heavily shaded part shows the region in which the electron density is greatest.

For measurement of relative inductive effects, hydrogen is chosen as reference in the molecule CR3–

H as standard.

If, when the H atom in this molecule is replaced by Z (atom or group), the electron density in the CR3 part

of the molecule is less in this part than in CR3– H, then

Z is said to have a –I effect (electron-attracting or electron-withdrawing).

If the electron density in the CR3 part is greater than

in CR3– H, then Z is said to have a +I Effect (electron-

repelling or electron-releasing)

e.g., Br is –I; C2H5 is +I.

Some common atoms or groups which cause +I or -I effects are shown below:

-I effect groups (Electron-attracting):

NO2, F, Cl, Br, I, OH, C6H5-

+I effect groups (Electron-releasing):(CH3)3C-, (CH3)2CH-, CH3CH2-, CH3-

Tertiary alkyl groups exert greater +I effect than secondary which in turn exert a greater effect than primary.

An inductive effect is not confined to the polarization of one bond. It is transmitted along a chain of carbon atoms, although it tends to be insignificant beyond the second carbon.

The inductive effect of C1 upon C2 is significantly less

than the effect of the chlorine atom on C1.

The inductive effect results in a permanent state of the molecule and can be observed practically in the form of dipole moments. The effect does not depend upon the presence of a reagent.

C C C Cl3 2 1 -I

It involves (pi) electrons of double and triple bonds.

The mesomeric effect (M Effect) refers to the polarity produced in a molecule as a result of interaction between two bonds or a bond and lone pair of electrons. The effect is transmitted along a chain in a similar way as are inductive effects.

Mesomeric or resonance effect

The mesomeric effect is of great importance in conjugated compounds. In such systems, the electrons get delocalized as a consequence of mesomeric effect, giving a number of resonance structures of the molecule.

Consider a carbonyl group (>C=0). The oxygen atom is more electronegative than the carbon atom. As a result, electrons of the carbon-oxygen double bond get displaced toward the oxygen atom. This gives the following resonance structures:

The mesomeric effect is represented by a curved arrow. The head of the arrow indicates the movement of a pair of electrons. If the carbonyl group is conjugated with a carbon carbon double bond, the above polarization will be transmitted further via the electrons.

The mesomeric effect like the inductive effect may be positive or negative.

Atoms which lose electrons toward a carbon atom are said to have a +M Effect.

+M effect groups: Cl, Br, I, NH2, OH, OCH3

Those atoms or groups which draw electrons away from a carbon atom are said to have a -M Effect.

-M effect groups: NO2, CN, >C=O

The mesomeric effect like the inductive effect results in a permanent state of the molecule. It does not depend upon the presence of a reagent.

The inductive and mesomeric effects indicate the charge distribution in a molecule. Thus, they provide an effective way of determining the point of attach of electrophile and nucleophiles on the molecule.

DRAWING RESONANCE STRUCTURES: PHENOL

Electromeric effectLike the mesomeric effect, it also involves the (pi)

electrons.

The electromeric effect (E Effect) refers to the polarity produced in a multiple bonded compound in the presence of a reagent.

When a double or a triple bond is exposed to an attack by an electrophile E+ (a reagent), the two electrons which form the bond are completely transferred to one atom or the other.

The electromeric effect is represented as:

The curved arrow shows the displacement of the electron pair. The atom A has lost its share in the electron pair and B has gained this share. As result, A acquires a positive charge and B a negative charge. Notice that the arrow points away from the centre of the bond and towards the atom that gains the electron pair.

Consider the example where an electrophile (E+) attacks a carbon-carbon double bond in the ethylene molecule. We know that the double bond is made up of one σ bond and one bond. The electrons in the bond are quite exposed. Under the influence of the electric field of the positively charged electrophile, the symmetry of the molecular orbital is disturbed entirely in favor of one carbon atom.

This gives a negative charge to the carbon atom to which the electron-pair migrates, while the other atom acquires a positive charge.

The electromeric effect is a temporary effect. It takes place only in the presence of a reagent.

Homolytic and heterolytic fissionEvery reaction of organic compounds involves the breaking (fission) of at least one bond and the making of another bond. To break a bond, in fact, we are breaking down a molecular orbital to give atomic orbitals.

We known that molecular orbitals are at a lower energy (more stable) than the atomic orbitals. Therefore, energy has to be supplied to break a bond. Assuming that sufficient energy is available, a covalent bond (σ bond) can undergo fission in two ways:

- Homolytic Fission or Homolysis

- Heterolytic Fission or Heterolysis

Homolytic fissionIn this process each of the atoms acquires one of the bonding electrons.

A B or A : B A B+

The products, A and B, are called free radicals. They are electrically neutral and have one unpaired (odd) electron associated with them. Free radicals are extremely reactive because of the tendency of this electron to become paired at the earliest opportunity. Homolytic fission is the most common mode of fission in the vapor phase.

Homolytic reactions are usually initiated by heat, light or organic peroxides.

Heterolytic fissionIn this process one of the atoms acquires both of the bonding electrons when the bond is broken.

A B A : B++ -

…………(1)

A B : A B+- +

…………(2)

In example 1, B is more electronegative than A which thereby acquires both the bonding electrons and becomes negatively charged. The arrow indicates that the sigma (σ) electrons that form the A — B bond are leaving A and becoming the exclusive property of B. In example 2, A is shown to be more electronegative than B.

The products of heterolytic fission are ions. Reactions which involve heterolytic fission take place at measurable rates. Heterolytic fission occurs most readily with polar compounds in polar solvents.

Reaction intermediatesHeterolytic and homolytic bond fissions result in the formation of short-lived fragments called reaction intermediates.Among the important reaction intermediates are:

- Carbonium ions

- Carbanions

- Carbon free radicals

- Carbenes

Carbonium ions (carbocations)Organic ions which contain a positively charged

carbon atom are called carbonium ions or carbocations. They are formed by heterolytic bond fission.

- where Z is more electronegative than

carbon

- Carbon bearing 6 electrons

- are lewis acid

The positively charged carbon atom in a carbonium ion uses sp2 hybrid orbitals to form three σ bonds. An empty p orbital extends above and below the plane of the σ bonds. This empty p orbital makes the carbon atom electron-deficient and gives it a positive charge. Thus a carbonium ion will combine with any substance (e.g., nucleophiles) which can donate a pair of electrons.

Structure of carbonium ion

Carbonium ions are named after the parent alkyl group and adding the words carbonium ion. For example,

The stability of carbonium ions is influenced by both inductive and resonance effects. For example, the allyl and benzyl carbonium ions are much more stable than propyl carbonium ions. Both allyl and benzyl carbonium ions can be stabilized by resonance as shown below but propyl carbonium ion (CH3CH2CH2

+) has no resonance forms:

Resonance forms of allyl carbonium ion:

CH2 = CH – CH2

+CH2 – CH = CH2

+

Resonance forms of benzyl carbonium ion:

Electron-releasing groups (+I Groups) also stabilize carbonium ions by dispersing the positive charge on carbon.

According to electrostatic theory, the stability of a charged system is increased by dispersal of the

charge.

Electron-attracting groups (-I Groups) like – NO2,

- Br will make a carbonium ion less stable.

Thus, a tertiary carbonium ion is more stable than-a secondary, which in turn is more stable than a primary because of the +I effect associated with alkyl groups.

Carbanions When an organic compound treated with a strong base, it is some times found that a hydrogen atom attached to a carbon atom is removed as a proton. The resulting ion containing a carbon atom with an unshared pair of electron is called a carbanion.

Organic ions which contain a negatively charged carbon atom are called carbanions. They are also formed by heterolytic bond fission.

R3C-H + B− → R3C− + H-B

where B stands for the base.

- Lewis base

- where Z is less electronegative than carbon

If the negatively charged carbon atom in a carbanion is bonded to hydrogens or alkyl groups (as in methyl or ethyl carbanion), it uses sp3 hybrid orbitals to form the three σ bonds.

If the negatively charged carbon atom in a carbanion is bonded to an unsaturated group (as in benzyl carbanion), it uses sp2 hybrid orbitals to form the three σ bonds.

The completely filled sp3 or p orbital makes the carbon electron-rich and gives it a negative charge. Thus a carbanion will combine with any substance (e.g., electrophiles) which can accept a pair of electrons.

Carbanions are named after the parent alkyl group and adding the word carbanion.

The stability of carbanions is also influenced by resonance and inductive effects.

For example, the benzyl carbanion is much more stable than propyl carbanion. This is because the benzyl carbanion can be stabilized by resonance. Propyl carbanion (CH3CH2CH2:

- ) has no resonance

forms.

Stabilization of carbanions by inductive effects is in the opposite direction from the carbonium ions. Electron-releasing groups (+I Groups) make the carbanions less stable. Thus a primary carbanion is more stable than a secondary, which in turn is more stable than a tertiary because of the +I effect associated with alkyl groups.

Benzyl carbanion

Electron attracting groups (-I Groups) like -NO2, -Br

will stabilize carbanion by dispersing of the negative charge on the carbon.

Carbon free radicalsIn contrast to carbonium ions and carbanions,

these have no charge. They are formed by homolytic bond fission.

Here Z and carbon atom have similar electronegativities.

R X R X

SP2 Hybridized

The carbon atom in a carbon free radical uses sp2 hybrid orbitals.

In chemistry, radicals (often referred to as free radicals) are atoms, molecules or ions with unpaired electrons on an otherwise open shell configuration.

In the context of atomic orbitals, an open shell is a valence shell which is not completely filled with electrons or that has not given all of its valence electrons through chemical bonds with other atoms or molecules during a chemical reaction.

Carbenes

Carbenes are neutral species having a carbon atom with two bonds and two electrons.

For example: Methylene (H2C:)

Carbenes are highly reactive. They act as strong electrophiles because they can accept a pair of electrons to complete their outer shell.

The carbon atom in a carbon free radical uses sp2 hybrid orbitals

Classification of reagentsOrganic reagents fall into two main groups:

-Electrophiles or Electrophilic Reagents

-Nucleophiles or Nucleophilic Reagents

Electrophiles

An electrophile is most simple an electron pair acceptor. Remember that an electron pair acceptor is a Lewis acid.

A reagent which can accept an electron pair in a reaction is called am electrophile. The name electrophile means “electron-loving” and indicates that it attacks regions of high electron density (negative centers) in the substrate molecule. Electrophiles are electron-deficient. They may be positive ions (including carbonium ions) or neutral molecules with electron-deficient centers.

e.g. H+, Cl+, Br+, I+, +SO3H , AlCl3 , BF3

An electrophile can be represented by the general symbol E.

Nucleophiles

A nucleophile is most simple an electron pair donor. Remember that an electron pair donor is a Lewis base.

A reagent which can donate an electron pair in a reaction is called a nucleophile. The name nucleophile means “nucleus-loving” and indicates that it attacks regions of low electron density (positive centers) in the substrate molecule. Nucleophiles are electron-rich. They may be negative ions (including carbanions) or neutral molecules with free electron pairs.

e.g. Cl-, Br-, I-, CN-, OH-, NH3 , RNH2, H2O, ROH

An nucleophile can be represented by the general symbol Z.

Types of organic reactions

The reactions of organic compounds can be classified into four main types:

1. Substitution reactions

2. Addition reactions

3. Elimination reactions and

4. Rearrangement reactions

1. Substitution reactionsSubstitution reactions are those reactions in which an atom or group of atoms directly attached to a carbon in the substrate molecule is replaced by another atom or group of atoms.

For example,

A hydrogen atom of the methane molecule is replaced by a chlorine atom.

In the above reaction, the bromine atom of ethyl bromide is substituted by a hydroxyl group.

These reaction may be initiated by a nucleophile, electrophile or free radical.

Organic substitution reactions are classified in several main organic reaction types depending on the intermediate involved in the reaction i.e. a carbocation, a carbanion or a free radical.

1a. Free radical substitution reactionsThese reactions are initiated by free radicals.

The chlorination of methane in the presence of ultraviolet light is an example of free-radical substitution.

uv

lightCH4 + Cl2 CH3Cl + HCl

The mechanism of the above reaction involves the following steps-

Initiation step: Heat or uv light cause the weak halogen bond to

undergo homolytic cleavage to generate two chloride radicals and starting the chain process.

Cl Cl Cl Cluv

light+

Propagation step: A chlorine free radical attacks the methane

molecule to give methyl free radicals and hydrogen chloride.

The methyl free radical attacks a chlorine molecule to yield methyl chloride and chlorine atom.

These propagation steps are repeated again and again.

Termination step: These involve the formation of stable molecules

by combination of free radicals.

1b. Electrophilic substitution reactions When a substitution reaction involve the attack by an electrophile, the reaction is referred to as electrophilic substitution.

The bromination of benzene in the presence of FeBr3 (lewis acid) is an example of electrophilic substitution.

The mechanism of the above reaction involves the following steps.Step 1: Formation of the electrophile

Step 2: The electrophile (Br+) attacks the benzene ring to form a resonance stabilized carbonium ion.

Step 3: Elimination of proton to give the substitution product.

Friedel-crafts alkylation and acylation reactions are the best example of electrophilic substitution reaction.

The formation of the electrophile

The electrophilic substitution mechanism

1c. Nucleophilic substitution reactionsWhen a substitution reaction involves the attack by a nucleophile, the reaction is referred to as SN (S stands for substitution and N for a nucleophile). A nucleophile is an the electron rich species that will react with an electron poor species.

The hydrolysis of alkyl halides by aqueous NaOH is an example of nucleophilic substitution.

R – X + OH– R – OH X–+Nucleophile Leaving

group

The nucleophilic substitution reactions are divided into two classes:

- SN2 Reactions

- SN1 Reactions

SN2 Reactions:

SN2 stands for bimolecular nucleophilic substitution.

When the rate of a nucleophilic substitution reaction depends on the concentration of both the substrate and the nucleophile, the reaction is of second order and is represented as SN2.

Rate α [Substrate] [Nucleophile]

Evidently, the rate-determining step involves the participation of both the substrate and the nucleophile.

It is a single step reaction. Single step reactions have no intermediates and a single transition state (TS).

Consider the hydrolysis of methyl bromide by aqueous NaOH. The reaction and the transition state are-

The hydroxide ion approaches the substrate carbon from the side opposite the bromine atom (backside attack). This is because both hydroxide ion and the bromine atom are electron rich. It is natural that these stay as far apart as possible (like charges repel).The transition state may be pictured as a structure in which both OH and Br are partially bonded to the substrate carbon. Also, the C—Br bond is not completely cleaved and C—OH bond is not completely formed. Hydroxide ion has a diminished negative charge because it has started to share its electrons with the substrate carbon.

The bromine atom also carries a negative charge because it has started removing its shared pair of electrons from the carbon atom. In the transition state, the three C—H bonds lie in one plane. The C—OH and C—Br bonds are perpendicular to the plane of C—H bonds.

The energy needed for the cleavage of C—Br bond is partially provided by the energy liberated by the C—OH bond formation.

In the course of the reaction, the configuration of the carbon is inverted, rather like an umbrella blown inside out. The change in configuration is called Walden Inversion.

SN1 Reaction :

SN1 stands for unimolecular nucleophilic substitution.

This pathway is a multi-step process.

When the rate of a nucleophiles substitution reaction depends only on the concentration of the substrate , the reaction is of first order reaction and is presented as SN1.

Rate α [Substrate]

Step 1:

The alkyl halide ionizes to give the carbonium ion. This is the rate determining step.

The carbonium ion is planar. This is because the central positively charged carbon atom is sp2 hybridized.Step 2:

The nucleophile can attack the planar carbonium ion from either side to give t-butyl alcohol.

Remember that the primary alkyl halide undergo hydrolysis by SN2 mechanism. The tertiary alkyl halide

undergo hydrolysis by SN1 mechanism. This is because

the attack of the hydroxide ion on the crowded tertiary alkyl halides is quite difficult.

Secondary alkyl halides may undergo hydrolysis by either SN1 or SN2 mechanism.

2. Addition reactionsAddition reactions are those in which atoms or groups of atoms are simply added to a double or triple bond without the elimination of any atom or other molecule.

These reactions may be initiated by-

- Electrophiles

- Nucleophiles

- Free radicals

2.a. Electrophilic addition reactions

When an addition reaction involves the initial attack by an electrophile, the reaction is referred to as electrophilic addition. Compounds containing carbon-carbon double and triple bonds undergo such reaction.

The addition of HBr to ethylene is an example of electrophilic addition.

The mechanism of above reaction involves the following stepsStep 1: Hydrogen bromide gives a proton (H+) and bromide ion (:Br –).

H Br H+ + :Br-

Electrophile Nucleophile

Step 2: The proton (electrophile) attacks bond of ethylene (ethene) to give a carbonium ion.

This step can also be written as-

CH2 CH2

Ethylene

H+ + CH3 CH2

+

Carbonium ion

Step 3: The bromide ion (Nucleophile) attacks the carbonium ion to give the addition product.

This step can also be written as-

Other reagents like HCl, HOCI, H2SO4,H2O, Br2, Cl2,

etc., add to alkenes similarly.

When an alkene is symmetrical about the double bond, as ethylene is, the product formed in addition reaction is the same no matter which way the reagent becomes attached to the alkene.

If, however, both the alkene and the adding reagent are unsymmetrical, two alternatives are possible:

CH3 CH CH2 + H BrCH3 CH CH3

Br

or

CH3 CH2 CH2 Br

(Isopropyl bromide)

(n-propyl bromide)

Experimentally it has been found that isopropyl bromide is the major product.

Markovnikov rule:

When an unsymmetrical reagent adds to an unsymmetrical double bond, the positive part of the reagent becomes attached to the double-bonded carbon atom which bears the greatest number of hydrogen atoms. Markovnikov rule can be rationalized in terms of modern mechanistic theory. Consider the addition of HBr to propene. The mechanism of this reaction involves the following steps.Step 1: Hydrogen bromide gives a proton (H+) and a bromide ion (Br–).

Step 2: The proton (electrophile) attacks the bond of propene to give a more stable carbonium ion.

H–Br Br:–H+ +

Step 3: The bromide ion (nucleophile) combines with the more stable secondary carbonium ion to give the major product.

CH3 CH CH3

(2o carbonium ion)

+:Br+ CH3 CH CH3

Br

(Isopropyl bromide)

-

Markovnikov rule may now be restated:

Addition of an unsymmetrical reagent to an unsymmetrical double bond proceeds in such a way as to involve the most stable carbonium ion.

Addition reactions (Ref: Morrison and Boyd):

1. Hydrogenation 2. Halogenation

3. Hydrohalogenation 4. Hydration

Anti-Markovnikov addition: Free radical addition reaction

2.b. Nucleophilic addition reactionsWhen an addition reaction involves the initial attack by an nucleophile, the reaction is referred to as nucleophilic addition. Aldehydes and Ketones which contain carbon-oxygen double bonds undergo such reactions.Carbon-oxygen double bond is highly polar in nature due to high electronegativity of oxygen compared to carbon. The carbonyl group may be represented as shown below-

The addition of HCN to acetone is an example of nucleophilic addition.

The mechanism of the above reaction involves the following steps-

Step 1: Hydrogen cyanide gives a proton and a cyanide ion (CN:).

H CN H+ + CN-

Step 2: The cyanide ion (nucleophile) attacks the positively charged carbonyl carbon to give the corresponding anion.

Step 3: The proton (electrophile) combines with the anion to form the addition product.

3. Elimination reactions

Elimination reactions are reverse of addition reaction.

Here two or four atoms or groups attached to the adjacent carbon atoms in the substrate molecule are eliminated to form a multiple bond.

One of them very often being a proton and the other a nucleophile.

The dehydrohalogenation of alkyl halides with alcoholic alkalis is an example of elimination.

These reactions are divided into two groups:

a) E2 Reactions

b) E1 Reactions

E2 Reactions:

E2 stands for bimolecular elimination. When the rate of an elimination reaction depends upon the concentration of a substrate and the nucleophile (base), the reaction is of second order and is represented as E2.

E2 like SN2 is also a one step process in which the

abstraction of the proton from the -carbon and the expulsion of the nucleophile from the α-carbon occurs simultaneously.

The mechanism of such a reaction is shown in figure-

Species that react as nucleophiles can also react as bases. Strong bases are defined by their ability to react with protons. Bases react with substrates to remove a proton that is on a carbon atom adjacent to the carbon atom containing the leaving group.

The leaving group is attached to the α carbon atom and the hydrogen that is removed is attached to a β (an adjacent) carbon atom.

These elimination reactions are called second-order elimination, E2, reactions. They are also referred to as β-elimination or 1,2-elimination reactions. If a halogen atom is the leaving group, the reaction is called a dehydrohalogenation reaction.

The rate of an E2 reaction is second order. The rate-law expression is the same as for the SN2 reaction:

Reaction rate = k [base] [substrate]

The order of reactivity of alkyl halides in E2 reactions is 30>20>10. This is opposite of the order seen for bimolecular SN2 reactions. Reasons are:

Greater the no. of -hydrogen for attack by base increase the chance of elimination, and

Higher the branched the alkene more stable the alkene.

E1 Reaction:

E1 stands for unimolecular elimination. When the rate of an elimination reaction depends only on the concentration of the substrate, the reaction is of first order and is designated as E1.

Step1: The alkyl halide ionizes to give the carbonium ion. (Slow process)

C

CH3

CH3

CH3

t-butyl bromide

BrC

CH3

CH3

CH3

+ + Br:-

Carbonium ion

E1 like SN1 reactions are also two step process.

Reaction rate = k [substrate]

Step2: A proton is abstracted by the base from the adjacent carbon atom to give alkene. (Fast process)

CCH2 H

CH3

CH3

OH:-

CH2

CH3

CH3

C+ + H2O

Carbonium ion 2-Methyl propane

The initial, rate-determining step is heterolytic cleavage of the carbon–halogen bond to give a carbocation and a halide anion.

The stability of carbocations is 30>20>10 and, therefore, 30 alkyl halides are more reactive than 20

alkyl halides.

Primary alkyl halides do not undergo E1 reactions since primary carbocations seldom, if ever, exist in solvent-based reactions.

Saytzeff Rule (or Zaitsev’s Rule)

Many molecules have more than one type of β hydrogen. As a result, β-elimination reactions can give different alkene products.

Alkene stability increases with increasing alkyl substitution of the alkene. Tetra alkyl-substituted alkenes are more stable than tri alkyl-substituted alkenes which are more stable than di alkyl substituted alkenes, and so on.

If the dehydrohalogenation of an alkyl halide can yield more than one alkene, then according to the Saytzeff Rule, the main product is the most highly substituted alkene.

For example, two alkenes are possible when 2-bromobutane is heated with alcoholic KOH.

According to the Saytzeff Rule the main product is the disubstituted alkene, 2-butene, rather than the monosubstituted, 1-butene.

In dehydrohalogenation the preferred product is the alkene that has the greater number of alkyl groups attached to the doubly bonded carbon atoms.

Important to rememberImportant to remember

Competition between Substitution & Elimination reactions

Four possible reaction mechanisms (SN1, SN2, E1,

and E2) can result from the reaction of nucleophiles or bases with halogenated substrates. Predicting which reaction will take place may seem like a daunting task at this point. Reactions even proceed by multiple, competing pathways. Here are some guidelines that can be used to predict the major reaction pathway.

Primary alkyl halides undergo only SN2

reactions with good nucleophiles. A good nucleophile that is also a strong bulky base, such as tert-butoxide, tends to give E2 reactions.

Tertiary alkyl halides undergo SN1, E1, and E2

reactions. E1 reactions are favored with weak bases (e.g., H2O) in polar protic solvents. E2 reactions are

favored with strong bases (OH−) and polar aprotic solvents. SN1 reactions occur with good nucleophiles in

polar protic solvents.Secondary alkyl halides are more difficult to predict since they can undergo all four mechanisms. Conditions favoring SN1/E1 reactions are weak

nucleophiles bases and polar protic solvents. Conditions that favor SN2 and E2 reactions are strong

nucleophiles/bases and polar aprotic solvents.