Stereochemistry B.Sc.II

1. Stereochemistry Prof. Jadhav Swapnil S.
Introduction:-
Stereochemistry  Chemistry in space. or Chemistry in three dimension.
The branch of Chemistry which deals with the study of three dimension
nature (special arrangement) of molecule is known as Stereochemistry.
The isomers which have same bond connectivity but have different
arrangement of group or atom in space are called stereoisomer’s or space
isomers and the phenomenon is known as stereoisomerism.
ISOMERS:- Different compounds having same molecular formula but different
structural formula.
Types of stereoisomerism.
1) Configurational Isomerism  Isomerism due to chiral centers in molecule.
2) Geometrical Isomerism  Isomerism due to restricted rotation around double
bond.
3) Conformational Isomerism  Isomerism due to free rotation around bond.
Conformational Isomerism:-
The isomers have same skeleton of group or atoms but have different special
arrangement of group or atoms due to free rotation around C-C are called
conformational isomers or conformers and the phenomenon is known as
Conformational Isomerism.
Alkane shows infinite no. of conformational isomers. These conformations are
momentary (temporary) but they are real structure.
The study of various aspects of conformations is called conformational
analysis.

2. Representation of conformations of ethane (Projection formulae):-
A Projection formula is suitable representations of molecule drown on paper.
A) Sawhorse Projection formula:-
(1) In Sawhorse Projection formula, C-C bond axis is drowning slightly inclined to
the plane of paper.
2) Lower left hand carbon represents front carbon.
Upper right hand carbon represents rear (back) carbon.
3) The atoms or group joined to C-atom are shown by three short lines.
4) The front and rear carbon are visible. 5) The Skew conformation cannot be
represented by this formula.
B) Dotted line wedge formula:-
1) Ordinary line (–) represents atoms present on the plane of paper.
2) Dotted line (----) represents atoms present behind the plane of paper.
3) Wedge ( ) represents atoms present above the plane of paper.
C) Newman Projection formula:-
1) In Newman Projection formula, C-C bond axis is drowning perpendicular to the
plane of paper.
2) Dot (.) represents front carbon. Circle (O) represents rear (back) carbon.
3) The atom attached to front carbon represented by full line. ( )
4) The atom attached to rear carbon represented by Brocken line. ( )

3. Representation of conformations of ethane and n-butane:-
Keeping rear methyl gr. Fixed, rotation about C-C bond can give infinite no. of
conformations. These conformations are broadly grouped into eclipsed, skew and
staggered conformation.
A) Eclipsed conformation:-
1) The conformation in which C-H bond on each carbon completely overlap with
each other and are at minimum distance is called Eclipsed conformation.
2) In ethane, eclipsing occurs at dihedral angle 00
, 1200
& 2400
producing three
conformations. But position of groups on both carbon remain same, they represent
single conformation.
B) Staggered conformation:-
1) The conformation in which C-H bond on C1 is exactly between two C-H bonds on
C2 and are at maximum distance is called staggered conformation.
2) In ethane, Staggered occurs at dihedral angle 600
, 1800
& 3000
producing three
conformations. But position of groups on both carbon remain same, they represent
single conformation.
In Eclipsed conformation the groups on C1 & C2 are at minimum distance
while in staggered conformation the groups on C1 & C2 are at maximum distance.
Hence they are called extreme conformations.
C) Skew or intermediate conformation:-
1) The infinite no. of conformations at dihedral angle other than 00
, 600
,1200
, 1800
,
2400
, 3000
& 3600
are collectively called Skew or intermediate conformations.
2) In Skew conformation, groups on C1 & C2 are at intermediate distance.

4. 3) They can suitably presented by only Newman Projection formula.
Conformations and Conformational analysis of ethane and n-butane:-
Because of some repulsive interaction between adjacent bond & atoms,
complete rotation about C-C bond is not possible. This produces infinite no. of
momentary stereoisomers.
As energy required for rotation is very low (1-20 kJ/mol) the given Conformations
are rapidly interconvert. Hence individual Conformation can not be isolated.
The stability, physical & chemical properties of molecule are affected by its
conformation.
“The study of energy associated with different conformations and its relation with
physical & chemical properties is known as conformational analysis.”
(I)Conformational analysis of ethane:-
Due to weak repulsive interactions, the rotation accompanied with change in
enthalpy.
The P.E. curve of ethane Conformers is shown bellow.

5. a) Eclipsed conformation:-
1) The three peaks at 00
, 1200
& 2400
indicates Eclipsed conformations. But position
of groups on both carbon remain same, they represent single conformation.
2) In Eclipsed conformation, the rear and front H-atoms are at minimum distance
(2.3 A) which is less than Van der waal’s radii (2.4 A). This introduces steric strain.
3) The rear and front C-H bond pair repulsion causes torsional strain.
4) Thus Eclipsed conformation is strained. For stability it acquires 12.0kJ/mol of
extra energy than stable conformation. Hence it is least favored conformation.
b) Staggered conformation:-
1) The 3 peaks at 600
, 1800
& 3000
indicates staggered conformations. But position of
groups on both carbon remain same, they represent single conformation.
2) In staggered conformation, the rear and front H-atoms are at maximum distance
which reduces steric strain.
3) The rear and front C-H bond pair repulsion less which reduce torsional strain.
4) Hence, staggered conformation is more stable & favored conformation.
c) Skew conformation:-
1) The other point on profile except 00
, 600
, 1200
, 1800
, 2400
, 3000
& 3600
indicates
Skew conformations.
2) In Skew conformation, groups on rear and front carbon are at intermediate
distance. Hence steric strain and torsional strain varies in between two extreme
conformations.
At room temperature the conformations overcome energy barrier 12kJ/mol.
Hence conformations constantly interconvert to attain a dynamic equilibrium
between them.

6. (II) Conformational analysis of n-butane:-
In n-butane (CH3-CH2-CH2-CH3), due to repulsive interactions, the rotation
accompanied with change in enthalpy. The P.E. curve of n-butane Conformers is
shown bellow.
(A) Eclipsed conformation:-
1) The three peaks at 00
, 1200
& 2400
indicates Eclipsed conformations.
2) Three peaks have two different heights & represent two different Eclipsed
conformations. a) Synperiplanar b) Anticlinal
a) Synperiplanar:-
i) The split peaks at dihedral angle 00
& 3600
represent Synperiplanar conformation.
It is fully Eclipsed conformation.
ii) In Eclipsed form, the bonds & atoms are at minimum distance. Hence
(a) Eclipsing between two bulky methyl groups produces strong steric strain.
(b) C-H bond interaction causes strong torsional strain.
iii) Hence it is highly strained one. For stability it acquires 18-25kJ/mol of extra
energy than stable conformation. Hence it is least stable and least favored
conformation.
b) Anticlinal:-
i) The two peaks at dihedral angle 1200
& 2400
represent 2 Anticlinal conformations.
But two peaks are of same height, they represent single conformation.
ii) In Eclipsed form, the bond & atoms are at minimum distance. But,
(a) Eclipsing between bulky methyl group & H-atom produces less steric strain.
(b) Weak C-H bond interaction causes less torsional strain.

7. iii) Hence it is less strained than Synperiplanar. For stability it acquires 4.7kJ/mol of
extra energy than stable conformation. Hence it is stable than Synperiplanar.
(B) Staggered conformation:-
1) The three valleys at 600
, 1800
& 3000
indicates staggered conformations.
2) The three valleys have two different heights and represent two different
staggered conformations. a) Antiperiplanar b) Gauchi
a) Antiperiplanar:-
i) The valley at 1800
indicates Antiperiplanar conformations.
ii) The rear and front methyl groups and H- atoms are at maximum distance. This
lowers steric and torsional strain.
iii) Hence it is least strained and least energetic. It is most stable & most favored
conformation. It is also called fully staggered.
b) Gauchi conformations:-
i) The valleys at 600
& 3000
indicate Gauchi conformations. But two peaks are of
same height, they represent single conformation.
ii) The rear and front methyl groups and H- atoms are at an angle 600
to each other.
The two methyl groups are relatively close than in antiperiplanar conformation.
This introduces some steric and torsional strain.
iii) Hence it is more energetic and less stable than antiperiplanar conformation.
It is also called partially staggered conformation.
(C) Skew conformation:-
1) The other point on profile except 00
, 600
, 1200
, 1800
, 2400
, 3000
& 3600
indicates
Skew conformations.
2) In Skew conformation, groups on rear and front carbon are at intermediate
distance. Hence steric strain and torsional strain varies in between two extreme
conformations.
At room temperature the conformations overcome energy barrier 18-25kJ/mol.
Hence conformations constantly interconvert to attain a dynamic equilibrium
between them.
The stability order is  Antiperiplanar > Gauchi > Skew > eclipsed.

8. Cycloalkanes relative stability:-
According to Le Bell and Vant Hoff, the geometry of C-atom is tetrahedral
having bond angle 1090
28’. The distortion in this bond angle causes strain making
molecule unstable.
Baeyer’s Strain Theory:-
1) All Cycloalkanes are planar in nature. ie. all C-atoms lie in same plane.
2) Planar disposition distorts the tetrahedral bond angle
3) This distortion causes angle strain & making molecule unstable. Baeyer
calculated total strain & distortion. [Distortion = ½(109 – actual angle)]
4) To overcome strain & attain stability molecule acquire high P.E.
5) Greater the angle strain greater the P.E. and lesser the stability.
6) A strained molecule relieves the strain by ring opening. This makes it more
reactive.
7) Higher ring have greater strain, so commonly not found in nature.
Note:- i) Bond angle < 1090
28’, stain is +ve. ii) Bond angle > 1090
28’, stain is -ve.
iii) Extent of strain depends on its magnitude and not on sign.
According to Baeyer’s
1) In Cyclopropane distortion and angle strain is maximum. It is least stable and
highly reactive. It is difficult to prepare.
2) In Cyclobutane distortion and angle strain is comparatively less. It is more
stable and less reactive than cyclopropane. It is prepared readily.
3) In Cyclopentane distortion and angle strain is minimum. It is most stable than
all cyclohexane and less reactive than cyclopropane. It is easily prepared in lab.
4) Cycloalkanes containing more than 5 Carbon not existing in nature.

9. Limitations:
1. Cyclohexane is more stable than Cyclopentane. Cyclopentane can be opened
up by catalytic hydrogenation at 573k but not Cyclohexane.
2. Distortion of Cycloheptane and Cyclobutane is nearly same but still
Cycloheptane is more stable.
3. Number of large ring systems commonly occurs in nature.
4. Cyclopentane and higher Cycloalkanes are almost equally stable.
5. According to this Cyclobutane ring can be formed more easily than
Cyclopropane. This is not true.
6. It cannot explain the observed heat of combustion of higher cycloalkanes.
7. Higher cycloalkanes are unusually stable. They show substitution reactions and
resemble open chain alkanes.
Baeyer’s Strain Theory failed to explain the stability of large ring because it
assumes all C-atoms of ring lie in one plane. It is only useful for cyclopropane.
Theory of Strain less Rings (Sachse-Mohr Theory):-
Sachse (1890) proposed that cyclohexane ring is not planar but it is puckered
to a chair and a boat form. This puckering restore tetrahedral angle, relieve the
internal strain and attain stability.

10. But he could not isolate these two forms his proposal is rejected. Mohr (1918)
suggested that a chair and a boat form are readily interconvertible and hence can
not be separated. He further proposed that, Decalin also exist in a chair and a boat
form but they are not easily interconvertible.
Sachse theory was revived by Mohr & extended to all other cycloalkanes. It is
called as Theory of strainless rings Or Sachse- Mohr theory.
It states that, “carbon atoms (C≤6) in cycloalkanes present in different
plane and restore normal tetrahedral angle and ring gets puckered.”
The ring free from angle strain is called strainless rings.
Huckel (1925) separate two forms of Decalin. Hassel (1943) point out that
Decalin is formed from chair form of cyclohexne.
Conformations and stability of Cyclohexane:-
Due to restricted rotation of C-C bond in ring, Cyclohexane shows limited
conformations. It exists in two prominent forms. A) Chair. & B) Boat.
A) Chair (rigid) conformation:-
1) It has a chair shape. Alternate C-atoms occupy two planes parallel to each other.
2) Each carbon has two types of C-H bond & H-atoms
a) Axial (a) & b) equatorial (e)
a) Axial C-H bond:-
i) This bond is perpendicular to plane of ring and parallel to axis of symmetry.
ii) The H-atom attached to axial bond is called axial hydrogen (Ha).
b) Equatorial C-H bond:-
i) This bond is parallel (side way) to plane of ring and perpendicular to axis of
symmetry.
ii) The H-atom attached to equatorial bond is called Equatorial hydrogen (He)
3) The 6 axial H-atoms alternately project above & down the plane of ring.
The 6 equatorial H-atoms form a belt around the ring.
4) The bond angle between any two bonds of carbon is 1090
28’.

11. B) Boat (flexible) conformation:-
1) It has a boat shape.
2) Four carbons (2, 3, 5, 6) lie in one plane while remaining two carbon (1, 4) lie
in one plane parallel to first plane.
3) In boat form 4 types of C-H bond & H-atoms are present.
a) The two C-H bonds on C1 & C2 coming towards each other are called flag-
pole bonds (fp) and the H- atoms joined to it is called flag-pole hydrogen.
b) The remaining two C-H bonds on C1 & C2 going away from each other are
called bow-spirit bonds (bs) and the H- atoms joined to it are called bow-spirit
hydrogen.
c) The four C-H bonds on C2, C3, C5 & C6 atoms forming the sides of the boat
are called quasi-axial bond(qa) while remaining four are called quasi-equatorial
bond (qe).
4) The bond angle between any two bonds of carbon is 1090
28’.

12. Twist boat conformation:-
It is obtained by twisting the boat conformation half way. Depending on direction
of twist boat conformation are formed as shown bellow (I) & (II)
Twist boat conformation is more stable than boat conformation.
Half-chair conformation:-
It is highly unstable transition state species. Hence cannot consider as conformation
Relative stability of Cyclohexane Conformers:-
Stability of Conformers α
𝟏
𝑷.𝑬
& P.E α internal strain.
Cyclohexane is exists as puckered (non- planar ring). Hence internal strain is
mainly due to 1) bond opposition strain. 2) Steric strain.
(A) Chair form:-
1. All C-H bonds are perfectly staggered, so bond opposition strain is minimum.
2. H-atoms are at minimum distance (2.3 A) which is less than Van der waal’s radii
(2.5 A). This minimizes steric strain.
3. Thus its P.E. is minimum and it is most stable & preferred conformation.

13. (B) Boat form:-
1. The C-H bonds forming side of the boat are in eclipsed position which causes
bond opposition strain.
2. The flag –pole hydrogen are close to each other (1.8 A°) than Van der waal’s radii
(2.5 A). This causes lot of steric strain.
3. Thus, it is slightly strained. Hence it is less stable & least preferred conformation.
(C) Skew (Twist)-Boat form:-
1. It is obtained by twisting the boat conformation half way. C2, C3 & C5, C6 are non-
planar.
2. This twisting leading to reduce torsional strain. Its energy is less than Boat form.
Hence it is more stable than Boat form.
(D) Half chair form:-
When chair form acquires some energy (29.71kJ/mol) it changes to Boat form
through highly unstable half chair form.
The energy barrier between the chair and half chair form is 46.04kJ/mol.
Average energy of cyclohexane is sufficient to overcome this barrier. So there is
dynamic equilibrium between different conformations. Hence it is not possible to
isolate them.

14. Stability order  Chair > twist Boat > Boat > Half chair.
At room temperature the chair conformation of cyclohexane interconvert
rapidly to its mirror image is called flipping.
During flipping, all equatorial bonds changes to axial bonds and vice-versa.
Conformations and stability of monosubstituted Cyclohexane:-
Cyclohexanol (C6H11OH):-
Cyclohexanol exist in two conformational isomers
i) Axial isomers  -OH gr. at axial position.
ii) Equatorial isomers  -OH gr. at equatorial position.
These two forms are in dynamic equilibrium through Boat form.
i) Axial isomer:-
The -OH gr. in axial position is very close to H-atoms of C3 & C5. It experience
lot of steric strain due to 1:3 diaxial repulsive interactions. Hence it is less stable
than equatorial isomer.

15. ii) Equatorial isomer:-
The -OH gr. in Equatorial position is away from H-atoms of C3 & C5. It reduces
steric strain due to least 1:3 diaxial repulsive interactions. It is more stable and
most preferred conformation.
At room temperature, both isomers are in dynamic equilibrium.
Axial isomer = 5% Equatorial isomer = 95%.
Bromocyclohexane (C6H11Br):-
Bromocyclohexane exist in two conformational isomers
i) Axial isomers  -Br gr. at axial position.
ii) Equatorial isomers  -Br gr. at equatorial position.
These two forms are in dynamic equilibrium through Boat form.
i) Axial isomer:-
The -Br gr. in axial position is very close to H-atoms of C3 & C5. It experience
lot of steric strain due to 1:3 diaxial repulsive interactions. Hence it is less stable
than equatorial isomer.

16. ii) Equatorial isomer:-
The -Br gr. in Equatorial position is away from H-atoms of C3 & C5. It reduces
steric strain due to least 1:3 diaxial repulsive interactions. It is more stable and
most preferred conformation.
At room temperature, both isomers are in dynamic equilibrium.
Axial isomer = 5% Equatorial isomer = 95%.
Methyl cyclohexane:-
Methyl cyclohexane exists in two conformational isomers.
i) Axial isomers  -CH3 gr. at axial position.
ii) Equatorial isomers  --CH3 gr. at equatorial position.
These two forms are in dynamic equilibrium through Boat form.
i) Axial isomer:-
The -CH3 gr. in axial position is very close to H-atoms of C3 & C5. It experience
lot of steric strain due to 1:3 diaxial repulsive interactions. Hence it is less stable
than equatorial isomer.

17. ii) Equatorial isomer:-
The -CH3 gr. in Equatorial position is away from H-atoms of C3 & C5. It reduces
steric strain due to least 1:3 diaxial repulsive interactions. It is more stable and
most preferred conformation.
At room temperature, both isomers are in dynamic equilibrium.
Axial isomer = 5% Equatorial isomer = 95%.
Locking of conformation in t-butyl cyclohexane:-
From mono-substituted cyclohexane it is evident that bulky group avoid axial
position. This is due to steric strain arising from 1:3 diaxial repulsive interactions.
However, energy barrier between axial & equatorial form is small, significant
no. of molecules do exist in axial form and there exist a dynamic equilibrium.
1. t-butyl gr. [-(CH3)3] is too bulky. In axial position the 1:3 diaxial interactions is
unbearable (very high).
2. Thus, t-butyl gr. has a tendency to maintain equatorial position & resist to
going axial position.
3. Hence it is called holding group because, it lock the cyclohexane ring in
equatorial conformation.

18. Stereoselective and Stereospecific reactions.
A reaction which gives predominantly one stereoisomer of several possible
diastereoisomers is called Stereoselective reaction.
A reaction in which stereochemically different molecules reacts differently to
form select stereoisomers is called Stereospecific reaction.
Stereochemistry of addition of halogen to alkenes (syn & anti-addition):-
Addition of bromine to 2-butene gives 2,3-dibromobutane.
2-butene exists as cis- and trans-geometrical isomers while 2,3-dibromobutane
exists in three stereoisomeric forms.
Cis-2-butene selectively forms recemic 2,3-dibromobutane (I) & (II). Hence it
is Stereoselective reaction.

19. Trans-2-butene selectively forms meso 2,3-dibromobutane. Hence it is
Stereoselective reaction.
In both reactions, Stereochemistry of reactants decides the product. Hence
this is also a Stereospecific reaction.
Syn-addition:-
When the added group becomes added to the same side of double of bond
is called Syn-addition.
Anti-addition:-
When the added groups become added to the opposite side of double of
bond is called Anti-addition.
Addition of Br2 to 2-butene involve anti addition.
1. Cis-2-butene on addition Br2 gives racemic 2,3-dibromobutane (mixture of
two enantiomers I & II)

20. 2. trans-2-butene on addition Br2 gives meso 2,3-dibromobutane.
Stereochemistry of elimination reaction (syn & anti-elimination):-
Dehydration of 1-bromo-1,2-diphenyl propane gives 1,2-diphenyl -1-propene.
Reactant (I) exist in two pair of Enantiomers (a & b) are called erythro And (c & d)
are called threo.
Note:- Erythro:- similar groups lie on same side of the formula.
Threo:- similar groups lie on opposite side of the formula.
The product also exist as a pair of stereoisomers Z (cis-isomes) & E (trans-isomers)

21. The erythro (a & b) always produce Z-alkene.
The threo (c & d) always produce E-alkene.

22. Syn- elimination:-
When the groups eliminated from same side to form double of bond is
called Syn-elimination.
Anti- elimination:-
When the groups eliminated from opposite side to form double of
bond is called Anti-elimination.
* Dehydration of alkyl halide is an example of Anti-elimination.
1. Erythro halide (a & b) on dehydration gives cis or Z- 1,2-diphenyl -1-
propene.
2. Threo halide (c & d) on dehydration gives trans or E- 1,2-diphenyl -1-
propene.