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Topic:

Effect of Structure on Reactivity of Compounds

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Introduction

Reactivity: “It is a term used in chemistry to describe the potential of a structure to undergo a chemical change.”

A change in structure corresponds to a chemical reaction.

Types of Structures Based on Reactivity:

Some chemical structures are more reactive than others. The greater a structure’s chemical potential, the greater is its reactivity.

Reactive Structures: Structures that are likely to undergo chemical change are said to be reactive. Structures that are highly reactive are generally unstable.

Unreactive Structures: Structures that are resistant to chemical change are said to be unreactive. Structures that are unreactive are generally stable.

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Activation Energy: The minimum energy requirement for reaction is known as the activation energy. It is a barrier over which molecules must pass if they are to react.

Potential energy (specifically, chemical potential) is the link between structure and reactivity.

Chemical potential is a form of energy that can be absorbed or released during a chemical reaction or phase transition.

Effect of Polarity on Reactivity: Charges and dipoles can help bring molecules together for reaction, helping them to overcome their electronic repulsion and lowering their activation energy. For example:

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Structure - Reactivity Relationships

Generally there are three main structure related considerations that affect the stability and reactivity of compounds. These are:

[1]. The nature of the chemical reaction which an organic molecule undergoes is dependent upon the functional groups present in the molecule.

It includes such factors as polarity, inductive effect, resonance etc.

[2]. Structural features in the molecule at sites that are not directly involved in a particular chemical transformation can affect both the kinetics and the equilibrium of the chemical reaction.

It includes such factors as steric effect, conjugation, hyperconjugation, saturation, unsaturation etc.

[3]. A substituent group already present on a benzene ring can affect both the reactivity of the ring toward electrophilic substitution and the orientation that the incoming group takes on the ring.

It includes such factors as electron donating groups (activators) and electron withdrawing groups (deactivators).

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Some of Cases are given with examples as follows:

[1]. Effect of Reactants on Reactivity:

Variations in the structure of the reactant may have a marked influence on the course of a reaction, even though the functional group is unchanged.

Thus, reaction of 1-bromopropane with sodium cyanide proceeds smoothly to yield butanenitrile, whereas 1-bromo-2,2-dimethylpropane fails to give any product and is recovered unchanged.

In contrast, both alkyl bromides form Grignard reagents (RMgBr) on reaction with magnesium.

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[2]. Effect of Reagents on Reactivity:

Apparently minor changes in a reagent may lead to a significant change in the course of a reaction.

For example, 2-bromopropane gives a substitution reaction with sodium methylthiolate but undergoes predominant elimination on treatment with sodium methoxide.

[3]. Effect of Stereospecificity on Reactivity:

Stereospecific Reaction: A reaction is termed stereospecific if starting materials differing only in their configuration are converted into stereoisomeric products.

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Example No. 1: Formation of different stereoisomeric products, as in the reaction of enantiomeric 2-bromobutane isomers with sodium methylthiolate is given as:

Example No. 2: Different rates of reaction, as in the base-induced elimination of cis & trans-4-tert-butylcyclohexyl bromide.

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[3]. Inductive Effects and Reactivity:

Any group or atom, which is highly electronegative (electron withdrawing) help in removing the hydrogen atom as proton. Hence (–I) effect group increases acidic strength.

And the group or atom which is less electronegative (electron donating) makes the removal of proton difficult. Hence (+I) effect groups decreases the acidic strength of carboxylic acid.

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Relative strength of the Organic acids:

Carboxylic acids have the tendency to release a proton and change into carboxylate anion. The acidic strength of carboxylic acid depends upon the ease with which it ionises to gives proton.
Any factor which stabilises the carboxylate ion will increase the acidic strength of the carboxylic acid.

Example : When we compare the acidities of ethanol and 2,2,2-trifluoroethanol, we note that the latter is more acidic than the former. Reason: Fluorine atoms are highly electronegative and help in removing the hydrogen atom as proton.

Example No. 2: Benzoic acid is stronger than acetic acid due to –I effect of phenyl group.

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[4]. Resonance Effect and Reactivity:

Resonance Effect: “The increase in electron density at one position with a corresponding decrease at another position by flow of electrons from one part of a conjugated system to the other is called resonance effect or mesomeric effect.”

The actual structure i.e., resonance hybrid of a molecule has lower energy than any of the contributing form and hence the resonance is a stabilizing phenomenon.
Example: The actual structure of carboxylate ion is the resonance hybrid of the two resonance structures as shown below:

The negative charge of the anion is dispersed. This resonance stabilization is responsible for the high acidity of carboxylic acids.

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Resonance is also an important factor that influences acidity. The acidity of H—A increases when the conjugate base A:¯is resonance stabilized.
In the example below, when we compare the acidities of ethanol and acetic acid, we note that the latter is more acidic than the former.

When the conjugate bases of the two species are compared, it is evident that the conjugate base of acetic acid (CH₃COO¯) enjoys resonance stabilization, whereas that of ethanol (CH₃CH₂O¯)does not so CH₃COOH is a stronger acid than CH₃CH₂OH.

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[5]. Steric Hindrance and Reactivity:

Steric Hindrance: “A lowering of the rate of a chemical reaction caused by the blocking of the reactive site of a molecule by adjacent atoms or groups of atoms is called steric hindrance.”
This effect is manifested when two or more groups or atoms come in close proximity to each other and the electronic cloud surrounding each atom repel each other. This makes the molecule unstable as well as hinders the attack of external reagents.

It affects different properties of molecules, like acidity, basicity and general reactivity.

Example: A substitution reaction on a tertiary alkyl halide such as 3-bromo-3-methyl hexane by potassium hydroxide does not work in this case because of steric hindrance.

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[6]. Effect of Substituents on Electrophilic Aromatic Substitution:

Electrophilic aromatic substitution:

Case No. 1: If a substituent that is already present on the ring makes the ring more electron rich by donating electrons to it, then the ring will be more reactive toward the electrophile and the reaction will take place faster. Such a group or substituent is called an activating group or substituent.

Case No. 2: On the other hand, if the substituent on the ring withdraws electrons, the ring will be electron poor and an electrophile will react with the ring more slowly. Such groups or substituents are called deactivating groups or substituents.

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Ortho–Para-Directing Groups and Meta-Directing Groups:

A substituent on the ring can also affect the orientation that the incoming group takes when it replaces a hydrogen atom on the ring.

Substituents fall into two general classes:

Ortho and para directors predominantly direct the incoming group to a position ortho or para to itself.
Meta directors predominantly direct the incoming group to a position meta to itself.

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[A]. Activating Groups/Ortho–Para Directors:

All electron-donating groups and the groups that have an unshared electron pair on the atom attached to the aromatic ring, such as amino (–NH₂), hydroxyl (–OH), alkoxyl (–OR), and amides (–NHCOR) or esters (–OCOR) etc. with the oxygen or nitrogen directly bonded to the ring, are powerful activating groups and are strong ortho–para directors.

Example No. 1 and 2:

Phenol and aniline react with bromine in water (no catalyst is required) at room temperature to produce compounds in which both of the ortho positions and the para position become substituted.

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Alkyl substituents are also electron-donating and activating groups. They are also ortho–para directors.

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[B]. Deactivating Groups/Meta Directors:

With the exception of halogen substituents, all electron-withdrawing groups e.g. –COOH, –CHO, >C=O, – CN, –NO₂ etc. are deactivating groups and all are meta directors.
Example: The nitro group is a very strong deactivating group and, because of the combined electronegativities of the nitrogen and oxygen atoms, it is a powerful electron withdrawing group and a meta director.
Nitrobenzene undergoes nitration at a rate only 10^-4 times that of benzene. When nitrobenzene is nitrated with nitric and sulfuric acids, 93% of the substitution occurs at the meta position. Reaction is as follows:

More Examples: The carboxyl group (CO₂H), the sulfonic acid group (SO₃H), and the trifluoromethyl group (CF₃) are also deactivating groups; they are also meta directors.

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[C]. Deactivating Ortho–Para Directors/Halogen Substituents:

The chloro and bromo groups are ortho–para directors. However, even though they contain unshared electron pairs, they are weakly deactivating toward electrophilic aromatic substitution because of the electronegative effect of the halogens.
Examples: Chlorobenzene and bromobenzene undergo nitration at a rate approximately 30 times slower than benzene.

The relative percentages of monosubstituted products that are obtained when chlorobenzene is chlorinated, brominated, nitrated, or sulfonated are shown below:

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[8]. Effect of Conjugation on Reactivity:

Conjugation: “Conjugation is overlap of p orbitals in neighbouring atoms separated by a sigma bond, resulting in delocalization of the p electrons.”

It may also be defined as “Special stability provided by electron delocalization in three or more adjacent, parallel, overlapping p-orbitals.”

It is typically seen in molecules with alternate single and double bonds.

A molecule with a conjugated double bond is more stable than a molecule with the same number of non-conjugated double bonds. It is due to electron delocalization over a molecule.

Delocalization reduces overall energy of the system. Lower the energy, higher is the stability, and lower is the reactivity.

More  extensive  conjugation leads to greater  stability of the molecule .

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[9]. Effect of Hyperconjugation on Reactivity:

Hyperconjugation: “The delocalization of σ-electrons or lone pair of electrons into adjacent π-bond or p-orbital is called hyperconjugation.”

Example: In Toluene, the methyl group releases electrons towards the benzene ring partly due to the inductive effect and mainly due to hyperconjugation.

Thus the reactivity of the ring towards electrophilic substitution increases and the substitution is directed at ortho and para positions to the methyl below.

The no bond resonance forms of toluene due to hyperconjugation are shown below.

From the above diagram, it can be seen clearly that the electron density on benzene ring is increased especially at ortho and para positions.

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Hyperconjugation and Stability of carbocations (Carbonium ions):

The ethyl carbocation, CH₃-CH₂⁺ is more stable than the methyl carbocation, CH₃⁺.

This is because, the σ-electrons of the α- C-H bond in ethyl group are delocalized into the empty p-orbital of the positive carbon center and thus by giving rise to ‘no bond resonance structures’ as shown below.

Whereas hyperconjugation is not possible in methyl carbocation and hence is less stable.

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[10]. Effect of Saturation and Unsaturation on Reactivity:

A saturated compound is a chemical compound that has a chain of carbon atoms linked together by single bonds. Saturated hydrocarbons are called alkanes.
An unsaturated compound is a chemical compound that contains carbon-carbon double bonds or triple bonds, such as those found in alkenes or alkynes, respectively.

Saturated Hydrocarbons: Saturated hydrocarbons are less reactive.
Unsaturated Hydrocarbons: Unsaturated hydrocarbons are more reactive.
Alkenes are more reactive than alkanes due to the exposed pi-bonding electrons.

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Saturated compounds preferably give substitution reactions.

Example: CH₄+ Cl₂ —> CH₃Cl + HCl

Unsaturated compounds preferably give addition reactions.
Example: Reaction between an alkene and water to form an alcohol. This reaction, called hydration, requires a catalyst—usually a strong acid, such as sulfuric acid (H₂SO₄):

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