effect of structure on reactivity of compounds.pdf

Effect of Structure on Reactivity of
Compounds
Muhammad Sajjad Hussain
Senior Lecturer COP, NMDC
Pharmaceutical Chemistry I
Organic Chemistry

Introduction
• Reactivity:
“It is a term used in chemistry to describe the potential of a
structure to undergo a chemical change.”
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.
1. Reactive Structures: Structures that are likely to undergo chemical change are
said to be reactive. Structures that are highly reactive are generally
unstable.
2. Unreactive Structures: Structures that are resistant to chemical change are
said to be unreactive. Structures that are unreactive are generally stable.
2

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).
3

[1]. Inductive Effects and Reactivity:
“Refers to the polarity induced in a molecule as a result of higher
electronegativity of one atom compared to another.”
 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.
4

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 ionizes to gives proton.
 Any factor which stabilizes 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.
5

[2]. 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.
6

 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.
7

8
[3]. 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.

[4]. 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.
9

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:
1. Ortho and para directors predominantly direct the incoming group to a position
ortho or para to itself.
2. 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.
11

 Alkyl substituents are also electron-donating and activating groups. They are also
ortho–para directors.
 Example No. 3: Toluene reacts considerably faster than benzene in all
electrophilic substitutions. Moreover, when toluene undergoes electrophilic
substitution, most of the substitution takes place at its ortho and para positions.
• E.g. When toluene undergoes nitration with nitric and sulfuric acids, toluene
reacts 25 times as fast as benzene and we get mono nitrotoluenes in the following
relative proportions:
Note: The same behavior is observed in halogenation, sulfonation, and so forth.
12

[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.
13

[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.
14

[5]. Effect of Conjugation on Reactivity:
• Conjugation: “Conjugation is overlap of p orbitals in neighboring atoms separated
by a sigma bond, resulting in delocalization of the p electrons.”
OR
• 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.
15

[6]. 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. 16

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.
17

[7]. 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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