Chapter 1:- Structure and Reactivity

B.sc 1st year Book
Organic Chemistry
(Page 13) 

# Organic reactions

Most of the molecules are stable with themselves and can be stored for years without any change in the reactions occurring. Molecules react because they move and one chemical reagent to another, chemical and bending of bonds have occurred When they move continuously in space, and collide with each other ion, stretching of the vessel and with the solvent molecules, if they are in solution. where collide each other with the walls stretches too much it may break and a chemical reaction. When one bond in a single molecule combines with the formation of a new bond and a chemical reaction the molecules collide, they may bond are broken and some new ones are formed this can not happen actions. Thus, in every reaction some, Therefore, the flow of electrons is the key to reactivity.

## Energy profile of a Reaction :

All organic molecules have an outer layer of many electrons that occupy filled orbitals (bonding and non all molecules repel each other. Reaction will occur only if the mother section between these electrons ensures that energy; Ea for the reaction) for the molecules to over if the molecules are given enough energy,(the activation
If two molecules lack the activation energy they will simply collide, and exchange energy bu. chemically unchanged. After collision electrons are moving in different directions at new velocities. Thus, not all collisions between molecules lead to the chemical change. If the reaction is to occur some, at least must have an energy greater than the activation energy or energy barrier.

### The electrostatic attraction brings molecules together.

In addition to repulsive forces, molecules possess some important repulsive forces if they are charged. In organic reactions such interactions are rare. A more common cause of organic reactions is an attraction between charged reagent (cation or anion) and an organic compound that has a dipole.
The reaction between sodium cyanide; NaCN (a salt) and a carbonyl compound and between KOH and alkyl chloride are good examples of organic reactions.
Thus, the presence of a dipole in a molecule represents an imbalance in the distribution of electrons due to polarization of σ or π bond or due to a lone pair of electrons or an empty orbital. When two molecules with complimentary dipoles, collide and together have the required activation energy to ensure that the collision is sufficiently energetic to overcome the general electronic repulsion, the reaction can occur.
Many organic reactions take place between completely uncharged molecules with no dipole moment. For example, the addition of bromine to an alkene. The attraction between these molecules is not electrostatic. It is due to an interaction between a filled π-orbital and an empty orbital ( antibonding orbital belongs to bromine, σ⋆ orbital of bromine-bromine bond). It is due to a special kind of interaction that leads to bonding. This type of attraction between organic molecules followed by the flow of electrons is the basis of organic chemistry. The electron pair donor is called_’nucleophile‘ and the electron pair acceptor as ‘electrophile‘. (organic reactions)

## HOMO-LUMO Interaction

The nucleophiles have the highest occupied molecular orbital(HOMO) which interacts with the lowest unoccupied molecular orbital (LUMO) of the electrophile. When LUMO and HOMO may be of the same energy and can then interact strongly. On the other hand, when the energy of LUMO is higher than that of HOMO, interaction will be less. There is an actual gain in energy when the electrons from the old lone pair drop down into a new stable bonding molecular orbital by the combination of old atomic orbitals. The energy gain is the greatest when the two orbitals HOMO and LUMO are the same and the least when they are very far apart in energy.
Organic reactions occur when the HOMO of nucleophiles overlaps with the LUMO of the electrophile to form a new bond. Thus, the nucleophile may donate the electrons from the lone pair; a π – bond or even a σ-bond and electrophile may accept electrons into an empty orbital or into the antibonding orbital of a π-bond (π∗-orbital) or even into antibonding σ-orbital ( σ∗). These antibonding orbitals are of low enough energy to react if the bond is polarised by a large electronegative difference between the atoms or even for unpolarised bonds if the bond is weak.

## Types of organic reactions :

Every organic reaction consists of a number of unit processes like bond formation, bond cleavage, acid-base equilibrium, etc. But for the sake of convenience, the classification of organic reactions in terms of overall processes can be made as :
Organic reaction are
II. Elimination Reactions
III. Substitution Reactions
VI. Rearrangement Reactions
V. Condensation Reactions
VI. Pericyclic Reactions
VII. Oxidation-Reduction Reactions

### I. Addition Reactions:

An addition reaction is one in which two substances combine to form a single compound. It is of the following types :

#### (a) Electrophilic Addition Reactions :

In electrophilic addition reactions, the electrophilic reagent adds to alkenes in a two-step process, an organic cation is formed in step I and reacts with a nucleophile in step II.
Example: Addition of HBr on ethylene molecule to form ethyl bromide.

#### (b) Nucleophilic Addition Reactions:

The addition of nucleophiles to carbonyl groups in aldehydes and ketones are a good example:

Example: Addition of HBr initiated by a peroxide on alkene to form alkyl bromide.
In this reaction peroxide used produces Bromo free radicals as follows-
1. ### Elimination Reactions:

An elimination reaction involves the removal of two atoms or groups from the same molecule. It is of the following types:

#### (a) α-Elimination Reactions:

Eliminations in which two atoms or groups are lost from the same atom are called ‘ α – Elimination reactions’.

#### (b) β-Elimination Reactions:

When two atoms or groups are eliminated from adjacent carbon atoms forming a double bond or triple bond, is called a ‘β-elimination reaction‘.
For example Dehydrohalogenation of alkyl halides with a strong base such as sodium ethoxide; C2H5O→Na+.

#### (c) γ – Elimination Reactions:

Such eliminations in which two atoms or groups are lost from γ – positions in a molecule and a three-membered ring is formed are called as’ γ-Elimination Reactions‘.

1. ### Substitution Reactions or Replacement Reactions :

A substitution reaction is one in which an atom or group in a molecule is replaced by another. The incoming group becomes attached to the same atom to which the outgoing was attached. It is the following types-

#### (a) Nucleophilic Substitution Reactions:

When the incoming species is a nucleophile and the leaving group departs with electron pair, it is called as ‘nucleophilic substitution reaction’.
For example :

#### (b) Electrophilic Substitution Reactions:

In this category, the incoming species is an electrophile and the leaving group departs with the pair of bonding electrons. For example Nitration of benzene.
1. ### Rearrangement Reactions :

A reaction in which an atom or group migrates from one atom to another resulting in a change in the basic skeleton of the molecule is called as ‘rearrangement reaction‘. These reactions are of two types-

#### (a) Intramolecular Rearrangements:

Those reactions in which the migrating group is never fully detached from the system in which it migrates are called as ‘intramolecular rearrangements‘.  For example :

(b) Intermolecular Rearrangements :

Rearrangements in which the migrating group becomes completely detached and later re-attached to the same or another molecule are called as intermolecular rearrangements.
For example:

The formation of these types of cross-products is due to intermolecular rearrangement.
1. ### Condensation Reactions :

Condensation reactions are those in which two molecules are combined together with the elimination of small molecules such as water or alcohol. For example :

2CH3COOC2H5 (ethyl acetate ) + C2H5O¯⟶ CH3COCH2COOC2H5(acetoacetic ester) +C2H5OH
Condensation is not a reaction of a special mechanism but consists of a combination of the reaction types so far described.
But in aldol condensation, two molecules of aldehyde are combined without elimination. The term condensation is sometimes used to indicate reactions in which carbon-carbon bonds are formed without elimination.

### 6. Pericyclic Reactions :

Pericyclic reactions are those involving the making and breaking of two or more bonds in a single concerted step through cyclic transition states.
Pericyclic reactions can be sub-divided into the following :
(ii) Electrocyclic Reactions
(iii) Sigmatropic Reactions
(iv) Ene-Reactions
(v) Cheletropic Reactions

### 7. Oxidation-Reduction Reactions :

#### (a) Oxidation Reactions :

Those reactions in which a compound undergoes oxidation are called as ‘oxidation reactions’. For examples :

#### (b) Reduction Reactions:

When a compound undergoes reduction then the reaction is called a ‘reduction reaction’. For example:
Disproportionation of two molecules of certain aldehydes leads to the oxidation of one and the reduction of the other as in Cannizzaro’s Reduction.

## Methods of determining Reaction mechanism :

An organic reaction mechanism is an actual process by which a reaction takes place. Various processes, the rate of each step, etc. should have to be taken into account. should have to know the stereochemistry of reactants as well as the solvent mechanism correctly, we system, etc. Various steps are involved in the determination of a moll as the solvent moles, the energy of the system, etc. Various steps involved in the determination of a reaction mechanism are discussed briefly.

### [1] Product analysis method :

Every first step (forward) while writing a mechanism is to make sure of the structure of the product. The molecules) by using atomic orbitals(AO’s) and combining them into (applied even to the most complicated structure of very small molecules and to deduce the structures of small parts of much larger molecules. The further basic structure along with the stereochemistry of product molecules are determined with the help of X-ray and spectroscopic Methods.

The fate of strategic individual atoms is studied by using isotope labeling with deuterium (D or H2), C,13 determining their relative quantities constitute the initial Identification of product, byproducts if any, and example; Any mechanism for the reaction that fails to account for the formation of a mechanism. For ethane can not be correct. Only the free radical mechanism accounts for the formation of a small amount of ethane as a by-product.

### [2] Determination of the presence of intermediate :

It has already been revealed that many organic reactions involve the formation of intermediates which can be sometimes isolated, detected by spectroscopic method or trapped by chemical reaction with an added compound.

#### (i) Isolation:

It is sometimes possible to isolate a stable intermediate from a reaction mixture by stopping the reaction after a short time, or by the use of very mild conditions. Three intermediates, for example: N- bromoamide (RCONHBr). its anion (RCONΘBr ) and an isocyanate (RNCO) have been isolated in the Hoffmann rearrangement.

#### (ii) Detection:

Various unstable intermediates are often detected by spectroscopic methods as in many cases, these can not be isolated. Intermediates like carbocations (−C+)in SN1reaction, cations, and anions in electrophilic and nucleophilic aromatic substitution reactions respectively, and the enols and enolates in various reactions of carbonyl compound can be detected by IR, NMR, and ESR and Raman spectra.

#### (iii) Trapping Reactions:

In some cases, the suspected intermediates can be trapped by running the reaction in presence of a compound that reacts with the intermediate. For can be trapped by running the reacts with dienes in the Diels-Alder adduct formation can be best used to detect its presence:

#### (iv) Addition of Suspected Intermediate:

If a certain intermediate is suspected, if it can be obtained by where means the addition of them into the same reaction conditions should give the same products.

### [3] Kinetic Method :

The rate of a homogeneous reaction is the rate of a disappearance of a reactant or the appearance of a product. If the rate is proportional to the change in concentration of only one reactant (A), the rate law is
 Rate =d[A]/dt=k1[A]

A reaction that follows such a rate law is called a first-order reaction. For a reaction that takes place in two or more steps, the rate of the overall reaction is the same as that of the slow step which is consequently called the rate-determining step. First-order kinetics shows that the reaction consists of more than one step and the rate law simply includes the reactant that participates in the slow step. Hydrolysis of tertiary butyl chloride s an example to form tert. butyl alcohol.

In this reaction, the rate depends on the concentration of tert. butyl chloride only.
 Rate = k1[(CH3)3C-Cl]
This means that the reaction is a multi-step process in which tert. butyl chloride is only involved in the rate-determining step. The presence of an intermediate (Here a carbocation (CH3)3C+ is therefore speculated). The rate of second-order reaction is proportional to the concentration of two reactants.
−d[A]/dt = k2[A][B]

−d[A]dt = k2[A]2 (If reactant A and B are the same) 
Hydrolysis of a primary alkyl halide (R−X) is a very good example of this kind. The rate expression for the reaction of methyl bromide with hydroxide ion is as follows-
−d[CH3Br]/dt = k2[CH3Br][OH−]
If the reaction follows simple second-order kinetics, indicative of a single-step process, it is assumed that a transition state is definitely involved. Thus, from kinetic studies, several mechanistic information can be derived.
[1] From the order of a reaction, information can be obtained about which molecules and how many take part in the rate-determining step. Such knowledge is very useful in elucidating a mechanism.
[2] The rate constant itself can tell us the effect on the rate of a reaction due to changes in the structure of the reactant, the solvent, the ionic strength, the addition of catalysts, etc.
[3] If the rate is measured at everal temperatures, in most cases a plot of k against 1/t is nearly linear with a negative slope and fits the equation ln⁡
k = −Ea/RT+ln⁡A.
From this equation Arrhenius activation energy; Ea can be calculated. ΔH can then be obtained by the following expression :
Ea=ΔH+RT
It is also possible to use these data to calculate the entropy of activation; Δ S by the formula
 ΔS±/4.576 = log⁡k−10.753−log⁡T + Ea/4.576T

Finally, ΔG± is obtained from the equation, ΔG± = ΔH± + TΔS±.
A positive ΔS means an increase in entropy or a decrease in order and a negative ΔS means an increase in order. The following conclusions can be made –
(i) If ΔS± is large positive, one molecule breaks into two or three.
(ii) Moderate negative value shows no change in the number of molecules or a bimolecular reaction with a solvent.
(iii) Large negative values show molecules go to one or unimolecular reaction with an ordered transition state.
[4] Isotope Effect or the Kinetic deuterium isotope Effect: When carbon-hydrogen bonds are being formed or broken in a rate-determining step of a reaction and hydrogen in that reaction molecule is replaced by deuterium (1D2), there is often a change in the rate. Such changes are known as ‘the deuterium isotope effects and are expressed by the ratio kH/kD. The ground state vibrational energy of a bond depends upon the mass of the atoms and is lower when the reduced mass is higher. Therefore, deuterium-carbon, deuterium-oxygen, deuterium-nitrogen bonds etc have lower energies in the ground state than the corresponding hydrogen-carbon, hydrogen-oxygen, hydrogen-nitrogen bonds etc respectively. Complete dissociation of a deuterium bond requires more energy than that for a corresponding hydrogen bond in the same environment. Consiquently, the deuterium molecule will react more slowly usually by a factor 2−3 ( i.e. kH/kD=2−3 ). For example, the rate determining step in the nitration of benzene is the attack of the electrophile on the benzene ring with a factor kH/kD=1.
This is easily be verified by replacing the hydrogen around the ring with deuterium. The rate of the reaction remains the scheme kH/kD=1.

In the iodination of phenol in basic solution, there is the deuterium isotope effect of kH/kD=4.7. This indicates the second step must be the rate-determining step.

## Secondary Isotope Effect :

The deuterium isotope effects have been found even where it is certain that the carbon-hydrogen bond does not break at all in the reaction. Such effects are called ‘secondary isotope effects. It can be divided into a-and β-effects. In the β-secondary isotope effect replacement of deuterium for hydrogen β-to the position of bond breaking shows the reaction. An example is the solvolysis of isopropyl bromide.

This effect is most likely due to hyperconjugation effects in the transition state. Because of hyperconjugation, the difference in vibrational energy between the carbon-hydrogen bond and the carbon-deuterium bond in the transition state is less than it is in the ground state. So the reaction is slowed down by the substitution of deuterium for hydrogen. When a new reaction is discovered, one or more mechanisms are proposed; the evidence is sought for and against these mechanisms until one emerges as the best choice. It remains accepted until fresh evidence comes along that does not fit the mechanism.
The general methods described in this chapter are not the only measure of determining mechanisms, it is important to emphasize here that all methods would not be used in one investigation as well.