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Steric Effect

The word “steric” is derived from ‘stereos’ meaning space. The amount of space that a group of atoms takes is called the "steric bulk".

Definition: “A steric effect is an effect (influence) on shape of molecule or on a reaction's course or the relative rate of reaction caused by the space-filling properties i.e. size or bulk of various parts (atoms or groups) of a molecule attached at or near the reacting site.”

Explanation:

Steric effects arise from a fact that each atom within a molecule occupies a certain amount of space. The electrons of the near atoms want to stay away from each other. When two or more atoms or groups get too close, this costs energy. It is so because the electronic cloud surrounding each atom repel each other. This repulsion makes the molecule unstable and also affect the molecule’s preferred shape (conformation) and reactivity.

Note: Steric effects are usually smaller than electronic effects (like resonance effect, electromeric effect, inductive effect etc.).

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Types of Steric Effects: Common steric effects includes Steric hindrance and Van der Waals strain (van der Waals repulsion).

[1]. Steric Hindrance: “Steric hindrance is a decrease in reactivity of compounds resulting from the presence of bulky groups at the site of a reaction.”

Steric hindrance occurs when the spatial arrangement and large size of atoms or groups within (at or near a reacting site of) a molecule hinders or retards a chemical reaction that is normally observed in related molecules with smaller groups.
A bulky group like -CH₃ ,–C₂H₅ ,–C₆H₅ , etc.can block a position.

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Example - 1: In an S_N2 reaction increasing the number and/or size of alkyl groups on the carbon bearing the leaving group (LG) causes more steric hindrance to backside attack in the transition state, leading to slower reaction rates.
The S_N2 reaction is fastest with unhindered halides.

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Explanation:

The carbon atom in bromomethane is readily accessible resulting in a fast S_N2 reaction.
The carbon atoms in bromoethane (primary), 2-bromopropane (secondary), and 2-bromo-2-methylpropane (tertiary) are successively more hindered, resulting in successively slower S_N2 reactions.
Methyl group occupies significant space, so when hydroxide ion approaches the central carbon atom, methyl group starts repelling the hydroxide ion.
Presence of two methyl groups makes it more tough. In the case of three methyl groups, reaction hardly occurs. So one can say that methyl group has steric effect on the hydroxide ion.

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Example No. 2: A substitution reaction of 1,5-dibromo-5-methylhexane with NaI. Note that substitution takes at carbon-1 and not at carbon-5 due to steric hinderance.

Example No. 3: A substitution reaction on a halide by a hydroxide does not work in the case given below because of steric hindrance. The second figure represents the same reaction, with spheres replacing the alkyl groups.

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Magnitude of Steric Hindrance: It is proportional to the size and number of substituents present in the vicinity of reaction site.

Steric Hindrance as a Useful Tool: It is often exploited by chemists to change the reactivity pattern of a molecule by:

stopping unwanted side-reactions (steric protection) or
by leading to a preference for one stereochemical reaction course.

[2]. Steric Strain/Van der Waals repulsion:

“The energetically unfavorable (repulsive) force resulting from the interaction of the bonded electrons of one molecule and those of another, or of the nuclei of one molecule with those of another is called Van der Waals repulsion.”

“Steric strain is an increase in potential energy of a molecule due to repulsion between electrons when big groups (occupying a large volume) are forced close to each other.”

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It is also called Van der Waals strain and is related to steric hindrance.

One of the most common forms of this strain is eclipsing hydrogen, in alkanes.
Example: The ethane molecule in the eclipsed conformation is said to suffer from torsional strain. (An eclipsed conformation is a conformation in which two substituents X and Y on adjacent atoms A, B are in closest proximity, implying that the torsion angle X–A–B–Y is 0°).

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Significance of Steric Effect

Steric effects affect the rates and activation energies of most chemical reactions to varying degrees.

Steric effects often dictate reaction pathways in organic synthesis because there are fewer configurations in which molecules can collide and successfully react.
Steric effect affects different properties of molecules, like acidity, basicity and general reactivity.

In biochemistry, steric effects are often exploited in naturally occurring molecules such as enzymes, where the catalytic site may be buried within a large protein structure.

In biological systems where everything occurs in the level of angstroms and in a very precise manner, steric effects even due to tiny H - atoms can result in the improper folding of proteins, leading to serious diseases like Alzheimer’s Disease (a type of dementia that causes problems with memory, thinking and behavior).

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Steric clashes can lead to improper DNA replication resulting is destruction of genetic information and hence to a large number of genetic diseases including cancer.

In pharmacology, steric effects determine how and at what rate a drug will interact with its target bio-molecules.

Steric hindrance between adjacent groups can also restrict torsional bond angles and so it can also affect the finally adapted molecular shape.

Steric effects are also important in aromatic substitutions.

Substitution does not occur to an appreciable extent between meta substituents if another position is open.

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Example: A good example of this effect can be seen in the nitration of m-bromochlorobenzene:

Only 1% of the mononitro product has the nitro group between the bromine and chlorine.

[10]. Steric strain inhibits the resonance. This phenomenon is known as steric inhibitions of resonance.

Due to bulky groups attached to a benzene derivative compound, the group attached to benzene goes out of plane and hence resonance is inhibited.

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Example: If we compare basicities of o-Toluidine and aniline, o-Toluidine is more basic than aniline.

Due to the bulky methyl group present on o-Toluidine, because electronic cloud of the methyl group repels the lone pair on nitrogen due to which it becomes difficult for this lone pair of electrons to be pulled into the ring.

So there is inhibition of resonance which increases the availability of nitrogen's lone pair for donation.

Hence, we can say o-Toluidine is more basic than aniline(as nitrogen lone pairs are in resonance with benzene).

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