Isomerism Notes

ISOMERISM

INTRODUCTION

• Isomers: Molecules with the same molecular formula but different arrangements of atoms.
• Isomerism: The phenomenon exhibited by isomers.
• Isomers have different physical and chemical properties.
• Classification of Isomerism:
  • Structural (Constitutional) Isomerism
    • Chain
    • Position
    • Functional
    • Metamerism
    • Ring chain
    • Tautomerism
  • Stereoisomerism
    • Optical
    • Geometrical

STRUCTURAL ISOMERISM

• Isomers: Compounds with the same molecular formula but different structural formulas.
• Isomerism: The phenomenon exhibited by structural isomers.

Types of Structural Isomerism:

Chain Isomerism:

• Chain isomers: Have the same molecular formula but differ in the number of carbon atoms in the parent chain (straight or branched).
• Examples:
  • Butane ($C<em>4H</em>{10}$):
    • n-Butane: $CH<em>3-CH</em>2-CH<em>2-CH</em>3$
    • Isobutane: $\begin{matrix} CH<em>3 \ | CH</em>3-CH-CH_3 \end{matrix}$
  • Butyl alcohol ($C<em>4H</em>9OH$):
    • n-Butyl alcohol: $CH<em>3-CH</em>2-CH<em>2-CH</em>2-OH$
    • Isobutyl alcohol: $\begin{matrix} CH<em>3 \ | CH</em>3-CH-CH_2-OH \end{matrix}$

Position Isomerism

• Compounds with the same molecular formula, carbon chain length, and functional group, but differing in the position of the functional group, multiple bond, or branches.
• Conditions:
  • Same molecular formula
  • Same carbon chain length
  • Same functional group
• Example:
  • Molecular formula: $C<em>3H</em>7X$ (where X = halogen, NH2, OH, or OR)
    • $CH<em>3-CH</em>2-CH_2-X$ (X is at the end of the chain)
    • $\begin{matrix} CH<em>3-CH-CH</em>3 \ | X \end{matrix}$ (X is at the middle carbon)
  • Propanol:
    • 1-Propanol: $CH<em>3-CH</em>2-CH_2-OH$
    • 2-Propanol: $\begin{matrix} CH<em>3-CH-CH</em>3 \ | OH \end{matrix}$
• In di-substituted benzene derivatives, position isomerism occurs due to the relative positions of substituents on the benzene ring (ortho, meta, and para).
  • Chlorotoluene ($C<em>6H</em>4(CH_3)Cl$):
    • o-Chlorotoluene
    • m-Chlorotoluene
    • p-Chlorotoluene

Functional Group Isomerism

• Isomers with the same molecular formula but different functional groups.
• Examples:
  • Molecular formula: $C<em>2H</em>6O$
    • Ethyl alcohol: $CH<em>3-CH</em>2-OH$ (Alcohol)
    • Dimethyl ether: $CH<em>3-O-CH</em>3$ (Ether)
  • Molecular formula: $C<em>3H</em>6O$
    • Propanal: $\begin{matrix} &amp; O \ CH<em>3-CH</em>2-C-H \ \end{matrix}$ (Aldehyde)
    • Propanone: $\begin{matrix} &amp; O \ CH<em>3-C-CH</em>3 \ \end{matrix}$ (Ketone)
  • Molecular formula: $C<em>3H</em>6O_2$
    • Propanoic acid: $\begin{matrix} &amp; O \ CH<em>3-CH</em>2-C-OH \ \end{matrix}$ (Acid)
    • Methyl acetate: $\begin{matrix} &amp; O \ CH<em>3-C-O-CH</em>3 \ \end{matrix}$ (Ester)
  • Molecular formula: $CH<em>3NO</em>2$
    • Nitromethane: $\begin{matrix} &amp; O \ CH_3-N-O \ \end{matrix}$
    • Methyl nitrite: $CH_3-O-N=O$

Metamerism

• Isomerism due to the different positioning of a polyvalent functional group (S, N, O, CO) in a molecule, with different alkyl groups around it.
• Members belong to the same homologous series.
• Examples:
  • Diethyl ether and methyl propyl ether:
    • Diethyl ether: $CH<em>3CH</em>2OCH<em>2CH</em>3$
    • Methyl propyl ether: $CH<em>3OCH</em>2CH<em>2CH</em>3$
  • Diethyl amine and methyl propylamine:
    • Diethyl amine: $CH<em>3CH</em>2-NH-CH<em>2CH</em>3$
    • Methyl propylamine: $CH<em>3CH</em>2CH<em>2-NH-CH</em>3$

Ring Chain Isomerism

• Isomerism due to differences in carbon chain or ring structures.
• Example:
  • Molecular formula: $C<em>3H</em>6$
    • Cyclopropane: $\begin{matrix} H<em>2C-CH</em>2 \ | \ CH_2 \end{matrix}$
    • Propene: $CH<em>3-CH=CH</em>2$

Illustration 1: Functional Isomers of Butanol

• Butanol shows functional group isomerism with ethers.
• Alcohols:
  • Butan-1-ol
• Ethers (R-O-R'):
  1. Ethoxy ethane (Diethyl ether)
  2. 2-Methoxy propane (Isopropyl methyl ether)
  3. 1-Methoxy propane (Methyl propyl ether)
• Isomeric Relations:
  • (1) and (2), (1) and (3), and (1) and (4) are functional isomers.
  • (2) and (3), and (2) and (4) are metamers.
  • (3) and (4) are positional isomers.

Illustration 2: Isomers of Pentanal

• Aldehydes show functional group isomerism with ketones.
• Aldehydes:
  1. Pentanal
• Ketones (R-CO-R'):
  1. Pentan-2-one (Methyl propyl ketone)
  2. Pentan-3-one (Diethyl ketone)
  3. 3-Methyl butan-2-one (Isopropyl methyl ketone)
• Isomeric Relations:
  • (1) and (2), (1) and (3), and (1) and (4) are functional isomers.
  • (2) and (3) are positional isomers.
  • (2) and (4) are position and chain isomers.
  • (3) and (4) are metamers.

Illustration 3: Isomers of Butanoic Acid

• Acids show functional group isomerism with esters.
• Acids:
  1. Butanoic acid
• Esters (R-CO-O-R'):
  1. Ethyl ethanoate (Ethyl acetate)
  2. Methyl propanoate (Methyl proplonate)
  3. Propyl methanote (Propyl formate)
  4. Propyl-2-methanonate (Isopropyl formate)
• Isomeric Relations:
  • (1) and (2), (1) and (3), (1) and (4), and (1) and (5) are functional isomers.
  • (2) and (3), (2) and (4), and (5) are metamers.
  • (3) and (4), and (3) and (5) are metamers.
  • (4) and (5) are position isomers.

Illustration 4: Functional Isomers of Butan-1-amine

• 1° amine ($RNH_2$):
  1. Butan-1-amine (n-Butyl amine)
  2. Butan-2-amine (sec-Butyl amine)
  3. 2-Methyl propan-1-amine (Isobutyl amine)
  4. 2-Methyl propan-2-amine (t-Butyl amine)
• 2° amine ($R-NH-R'$):
  1. N-Methyl propan-1-amine (Methyl propyl amine)
  2. N-Ethyl ethan-1-amine (Diethyl amine)
• 3° amine ($R-N(R')-R''$):
  1. N-Methyl propan-2-amine
  2. N,N-Dimethyl ethan-1-amine (N,N-Dimethyl ethyl amine)
• Isomeric Relations:
  • (1° and 2° amine), (1° and 3° amine), and (2° and 3° amine) are functional isomers.
  • 2° amine and other isomeric 2° amine are metamers.
  • 3° amine and other isomeric 3° amine are metamers.
  • But 1° amine and other isomeric 1° amine are position or chain isomers.
  • (2) and (2), (1) and (3), (1) and (4), and (1) and (5) as functional isomers.
  • (2) and (3), (2) and (4) and (4) are metamers.
  • (2) and (5), (3) and (5), and (4) and (5) are functional isomers.

TAUTOMERISM

• A phenomenon where a single compound exists in two readily interconvertible structures, differing in the position of at least one atomic nucleus (usually hydrogen).
• Tautomeric structures are obtained by the simultaneous shift of an H atom and a double bond (π-bond) at 1 and 3 positions (1,3-shift).
• Also called desmotropism, dynamic isomerism, kryptomerism, allelotropism, or metrotropy.

Difference Between Resonance and Tautomerism:

• Resonance is hypothetical; tautomerism is real.

• Resonance-contributing structures cannot be isolated; tautomeric structures can be isolated.

• In resonance, atom positions are fixed; in tautomerism, an H atom and π-bond shift at 1,3-positions.

• Tautomeric forms have different functional groups; resonating structures have the same functional group.

• Tautomeric forms have no effect on bond lengths; resonance affects bond length.

• Resonance structures are obtained by delocalization of π or non-bonding electrons; tautomeric structures by delocalization of σ- and π-bonds.

• Dyad System: H atom oscillates between two polyvalent atoms linked together.

• Triad System: H atom moves from the first to the third atom in a chain.

Dyad System Example:

• Hydrocyanic acid; H atom oscillates between C and N atoms.
  • $H-C≡N$ Hydrocyanic acid
  • $H-N≡C$ Isohydrocyanic acid

Triad System:

Keto-Enol System:

• Polyvalent atoms are O and two C atoms.

• Arises due to 1,3-migration of a hydrogen atom from one polyvalent atom to the other within the same molecule.

• Isomers exist in dynamic equilibrium (tautomers); phenomenon called tautomerism.

• One form contains the keto group (>C=O); the other contains the enolic (>C=C–OH) group.

• Examples:

  • Acetaldehyde:
    • Keto form: $CH_3CHO$
    • Enol form: $CH_2=CHOH$ (negligible amount)
  • Acetone:
    • Keto form: $CH<em>3COCH</em>3$
    • Enol form: $CH<em>2=C(OH)CH</em>3$ (negligible amount)

• In simple aldehydes and ketones, the enolic form is stabilized by intramolecular hydrogen bonding (chelation), especially in 1,3-dicarbonyl compounds.

  • Acetoacetic ester (7% enolic form):
    • Keto form (93%): $\begin{matrix} &amp; O \ CH<em>3-C-CH</em>2-C-O-Et \ \end{matrix}$
    • Enol form (7%): $\begin{matrix} &amp; OH &amp; O \ CH_3-C=CH-C-O-Et \ \end{matrix}$
  • Acetyl acetone (76% enolic form):
    • Keto form (24%): $\begin{matrix} &amp; O \ CH<em>3-C-CH</em>2-C-CH_3 \ \end{matrix}$
    • Enol form (76%): $\begin{matrix} &amp; OH &amp; O \ CH<em>3-C=CH-C-CH</em>3 \ \end{matrix}$
    • More stable due to the 5-membered ring and intramolecular H-bonding.

• Effect of solvent on enol content:

  • 15% in $H_2O$; 92% in hexane.
  • $H_2O$ forms H-bonds with (C=O) of keto form, inhibiting intramolecular H-bonding of the enol form.
  • Enol content increases in non-polar aprotic solvents and decreases in polar protic or polar aprotic solvents.
  • Enol content order in different solvents: Hexane > benzene > acetone > methanol > $H_2O$.
  • Enol content is more volatile; separated by careful distillation.

• Essential conditions:

  • Aldehyde or ketone must have at least one α-hydrogen atom to exhibit keto-enol tautomerism.
  • Acetophenone, butan-2-one, and propanal show tautomerism.
  • Benzaldehyde and benzophenone do not show keto-enol tautomerism because of the absence of α-hydrogen atoms.

• Keto-form:

  • Forms oximes, hydrazones, and gives DNP test (presence of C=O group).

• Enolic-form:

  • Gives a color with neutral $FeCl_3$ solution (test of enolic compounds).
  • Decolourises $Br<em>2/CCl</em>4$ solution (test of unsaturation due to C=C bond).
  • Forms acetyl derivative (presence of –OH group).

• Tautomerism occurs in both acidic and basic mediums.

Mechanism of Acid/Base Catalyzed Tautomerism:

• Acid-catalyzed tautomerism:
  • (Keto form) $\rightleftharpoons$ (Enol form)
  • α-H atoms are acidic due to electron-withdrawing (C=O) group.
• Base-catalyzed tautomerism:
  • (Keto form) $\rightleftharpoons$ (Enol form)

Triad System Containing Nitrogen

• Nitro-isonitro tautomerism:
  * (Nitro form) $\rightleftharpoons$ (Isonitro or aci form)

  • Lactam-lactim tautomerism:
    • (Lactam) $\rightleftharpoons$ (Lactim)
  • Enamine-ketimide tautomerism:
    • (Enamine) $\rightleftharpoons$ (Ketimide)

• Tautomerism of nitrous acid:
  * $H-O-N=O$ (Nitro form) $\rightleftharpoons$ $O=N-O$ (Nitro form)

• Nitroso-isonitroso tautomerism:
  * $CH<em>3-N=O$ (Nitroso) $\rightleftharpoons$ $CH</em>2=N-OH$ (Isonitrioso)

• Increasing Order of Enol Content:

  • Aldehyde (MeCHO) < ketone ($MeCOMe$) < ketoester ($CH<em>3COH</em>2COOC<em>2H</em>5$) < ketoester with (Ph) group ($PhCOCH<em>2COOC</em>2H<em>5$) < dial (OHC–CH2–CH2–CHO) < keto–aldehyde ($CH</em>3COCH<em>2CHO$) < diketone ($CH</em>3COCH<em>2COCH</em>3$) < (Ph) group containing e- donating group with (C=O) group
  • $\begin{matrix} &amp; &amp; O \ MeO-C-CH<em>2-C- \ \end{matrix}$ << $\begin{matrix} & & O \ Ph-C-CH</em>2-C-Ph \ \end{matrix}$ << $\begin{matrix} &amp; &amp; O \ O<em>2N-C-CH</em>2-C-Ph \ \end{matrix}$

Illustration 5: More Stable Tautomerism Structures

• Phenol:
  • Keto form is less stable due to loss of aromaticity.
  • Enol form (phenol) is more stable than keto form (cyclohexa-2,4-dien-1-one) due to aromaticity.
• Methyl-3-oxobutanoate:
  • Enol form is more stable due to hydrogen bonding between the OH group and carbonyl carbon.
  • More substituted alkene is more stable.
  • Extended conjugation between (C=O) and (C=O).
  • Further stabilized by chelation by intermolecular H-bonding.
• Cyclohexan-1,3,5-trione:
  • Enol form is more due to gain of aromatic structure (1,3,5-Trihydroxy benzene or Phloroglucinol).

Illustration 6: Decreasing Order of Enol Content

• Both (B) and (A) are stabilized by intramolecular H-bonding.
• (B) shows more enol content than (A) since (B) is more substituted alkene.
• In (C), there is only one α-H atom and its acidity is decreased by e donating (+I effect of) isopropyl group. It shows less enol form.
• Decreasing order: b > a > c.
• $\begin{matrix} &amp; &amp; O &amp; O \ Me-C-CH<em>2-C-Me \ \end{matrix}$ > $\begin{matrix} & & O & & O \ Me-C-CH</em>2-C-CH(Me)_2 \ \end{matrix}$

Illustration 7: Enol Content of Butane-2,3-dione, Butan-2-one, and Cyclohexane-1,2-dione

• Biacetyl (A):
  • Adjacent (C=O) groups destabilize the molecule due to electrostatic repulsion.
  • Molecule relieves some repulsion by acquiring anti conformation.
  • Enol form relief occurs at the expense of loss of (C=O) resonance energy.
• Butan-2-one (B):
  • No other factor except the loss of resonance energy occurs during enolisation.
• Cyclohexane-1,2-dione (C):
  • The cyclohexane ring is rigid, and the –σ charge on the adjacent (C=O) groups is in syn-position.
  • Molecule relieves its electrostatic repulsion only by the enolisation of one of the (C=O) groups.

Illustration 8: Decreasing Order of Enol of Ethyl Acetoacetate in Solvents

• Enol content increases in non-polar aprotic solvent (e.g., benzene or hexane) and decreases in polar protic or polar aprotic solvent.
• Order: Benzene (non–polar) > acetone (slightly polar) > methanol (polar, protic solvent) > $H_2O$ (higher polar, protic solvent).

Illustration 9: Decreasing Order of Enol Content

• (A) CH_2(COOEt)_2 (Diethyl malonate)
• (B) CH_3COCH_2COOEt (EAA)
• (C) CH_3COCH_2COCH_3 (Diketone)
• (D) PhCOCH_2COCH_3
• Sol: Decreasing order: d > c > b > a (89% > 7.7% > 1%) (diketone with (ph) group > diketone > keto ester > diester)

STEREOISOMERISM

• Compounds with the same molecular and structural formula but different arrangements of groups or atoms in space.
  • Configuration isomerism
  • Conformational isomerism

Configuration isomerism is further divided into two parts:

• Geometrical isomerism
• Optical isomerism

GEOMETRICAL ISOMERISM

• The main criteria for geometrical isomerism is the restriction in rotation:
  • In alkenes, (C=C) bond is made of σ –and π –bonds.

Types of geometrical isomerism:

• Cis–Trans Isomers
• E–Z Isomerism
• Syn–Anti Isomerism

Cis–Trans Isomers

• Similar groups or atoms lie on the same side (cis) or opposite sides (trans) of the double bond or restricted rotation site (cycloalkanes).
• Examples:
  • But-2-ene:
    • cis-But-2-ene
    • trans-But-2-ene

Properties of cis–trans isomer

• Stability: Cis < Trans
• Dipole moment:
  • µ(Sym trans)=0 (unsym trans) µ < cis isomer
• Polarity: Cis > Trans
• Solubility: Cis > Trans
• Boiling point: Cis >Trans
• Melting point: Cis < Trans
• Heating effect:
  • Maleic acid from anhydride at 100oC but fumaric acid forms anhydride at 250oC

E–Z Isomerism

• Applicable when cis-trans nomenclature is insufficient.
• E → Entegen (opposite)
• Z → Zusamann (same)
• E-form: Highest priority groups are on opposite sides of the double bond.
• Z-Form: Highest priority groups are on the same side of the double bond.

Priority Rule (Cahn-Ingold-Prelog):

• Rule 1: Atoms with higher atomic numbers have higher priority.
• Rule 2: If atomic numbers are the same, higher atomic weight has higher priority.
• Rule 3: For identical atomic number and weight, priority is decided by the next joining atom.
• Rule 4: Multiple bonded groups are considered as follows:

Syn-Anti Isomerism

• Oximes of aldehydes and unsymmetrical ketones show geometrical isomerism.
  • Syn Form: -OH group and H atom on the same side of the C=N double bond.
  • Anti Form: -OH group and H atom on opposite sides of the C=N double bond.
• In unsymmetrical Ketoxime, if –OH and the alphabetically alkyl present on the same side of double bond, then it is syn form and other isomer is anti form.
• Geometrical isomerism in AZO compounds:
  • $\begin{matrix} Ph-N=N-Ph \ \end{matrix}$

Geometrical Isomerism in Cyclic Compounds

• Restriction in rotation about bonds in cycloalkanes.
  • HOOC COOH is Cis form
  • COOH HOOC is Trans form

Illustration 10: Arrange the following ligands in the decreasing order of priority

• Concept Explanation:
  • According to CIP rules priority is to be given to atomic numbers but in case they have same atomic number, i.e., isotopes, then priority is to be given to molecular weights.
• Example:
  • (i): ($-CH(CH<em>3)</em>2$)
  • (ii):

Illustration 11: Assign E–Z configuration to each of the following

• (Z) Priority of HC≡C–>–CMe3 and priority of CH2 = CH–>–CHMe2 . So two higher priority groups on sameside, hence Z–configuration.
• (E) Priority of > , and . So two higher priority groups on opposite sides, henceC2H5ClCH3CH2–>MeE–configuration.

Illustration 12: Give the decreasing order of net dipole moments of the following

• Explanation of Concept
  • I>II>III (I) has a smaller angle of separation between two Br atoms than in (II) and (III). Resulting in more net dipole moment (µ).

Illustration 13: Give the structural and diastereomers of pent–1–ene

• Concept Used:
  • Write the C–skeletons and introduce double bond. The possible structures are:

OPTICAL ISOMERISM

• Compounds which can rotate plane polarised light, are called optically active compounds and this phenomenon is called optical activity.

Specific Rotation:

The number of degrees that the plane of polarization is rotated as the light passes through a solution of an enantiomer depends on the number of chiral molecules that it encounters. in order to place measured rotations on a standard basis, chemicals calculate a quantity called the specific rotation, [α], by the following equation: [ ] c.l α α =  

Van’t Hoff rule:

According to Van’t Hoff rule, Total number of optical isomers should be = $2^n$, where n is number of chiral centre(s).

Chirality

• A molecule without any elements of symmetry.
• Asymmetrical carbon is a chiral center.
• Conditions for optical activity
  • Conditions for optical activity

R–S System (Absolute Configuration)

• R→ Rectus (Right)
• S→ Sinister (Left)

ENANTIOMERS

• Those compounds which are nor superimposable on their mirror image, is called enantiomeric pairs.
• Condition → same molecular formu, same structure formul, different configuration.

Properties of enantiomers:

• Their physical properties are different like mpt, bpt, density, solubilities & values of specific rotation.
• They exhibit similar but not identical chemical behaviour

Diastereomers

• Characteristic of Diastereomers
  • Characterstic of Diastereomers ● Generally optical active, however geometrical isomers are an exception.

Racemic Mixture and Optical Resolution

• The process of separation of a racemic mixture into its (+) and (–) enantiomers is called resolution. Since, the enantiomers have identical physical and chemical properties except towards optically active reagents, they cannot be separated by the usual techniques such as fractional crystallization, fractional distillation, chromatography, etc. Therefore, special methods are used to achieve their separation

Diastereomeric method:

• One of the most common methods is to allow a racemic mixture to react with an enantiomer of some other compound. This changes a racemic form into a mixture of diastereomers which have different solubilitys as well as melting and boiling points. These can be separated from one another by conventional methods of separation of compounds. The separated diastereoisomer is then broken down to give pure enantiomers.

Racemic Forms and Enantiomeric Excess

• Moles of one enantiomer Moles of other enantiomer % Enantiomeric excess 100 Total moles of both enantiomers − = × * Enantiomeric Excess*
• The enantiomeric excess can be calculated from optical rotations:

Chirality in Compounds with No Optical Centres

• Stereochemistry of C Compounds Not Containing an Asymmetric C Atom (Allenes)
  H Br C = C = C Br H ( A) 1,3–Dibromo allene also shows optical Activity
• Cyclic system:
  • By sufficiently large groups, free rotation about the single bond joining the two phenyl groups is no longer possible, proy are large enough, onlyided.

Formula for the number of optical isomers

• Optical isomers When terminal groups are different 2n (where n is the no. of asymmetric C atoms) When terminal groups are same When n is even, When n is odd

Illustration 14: Specify the configuration of following compounds in D or L

• Solution:
  • Based on D or L configuration

Illustration 15: b. Which of the following are optically active compounds and why?

• Solution:
  • (C) Shows optical activity.

Illustration 16: Write the name and structure of the following optically active compounds with lowest molecular weight.

• H HC C F C H (Flurobutane)

Illustration 17: How many stereoisomers are possible for the compound CH3CH = CHCHClCH3?

• 4 stereoisomers are possible for this compound

CONFORMATIONAL ISOMERISM

• Different non–identical arrangement of atoms or group in a molecule that result by the rotation about a single bond and that can easily be reconverted at room temperature are known as conformational stereoisomers of conformers

Formula of Ethane:

• Ethane molecule contains an infinite number of conformers.

Conformation of Butane:

• If the dihedral angle is less than 60, it is known as skew. stability Partial eclipsed stability > Fully eclipsed stability

Illustration 18: Assign R and S configuration of the following compound

• ( R) gives Anti clockwise(S). With one interchange, the configuration changes from (S) to (R) H

Illustration 19: Give the effect of the configuration of (S)–2–bromo butane on performing the following operations

• Concept used:
  • Priority order Br > C2H5 H.
  • f. This type of operation is also not allowed in Fischer projection.