FY BSC (USCH-102)Revised syllabus of University of Mumbai (2016-17)

Semester I paper IIStereochemistry-I

Dr. Anita S. Goswami-Giri

VPMs B N Bandodkar College of Science Thane.

anitagoswami@yahoo.com

Stereochemistry 1

DEFINITIONS1) Stereoisomers - Compounds that have the same molecular formula and the same connectivity, but different

arrangement of the atoms in 3-dimensional space. Stereoisomers cannot be converted into each other

without breaking bonds.

2) Enantiomers - Nonsuperposable mirror images, or chiral molecules which are mirror images.

3) Diastereomers - Stereoisomers which are not enantiomers (or not mirror images) ; different compounds

with different physical properties

4) Chiral, or asymmetric carbon - A tetrahedral carbon (sp3 carbon) atom bearing four different substituents.

5) Chirality centers, or stereocenters - Asymmetrically substituted atoms in a molecular structure.

The most common type encountered in this course will be the chiral carbon described above.

6) Meso compounds, or meso forms - Symmetric, or achiral molecules that contain stereocenters. Meso

compounds and their mirror images are not stereoisomers, since they are identical.

Stereochemistry 2

7) Optical activity - The ability of chiral substances to rotate the plane of polarized light by a specific angle.

Or (achiral compound will not rotate light)

a. Dextrorotatory - Ability of chiral substances to rotate the plane of polarized light to the right.

b. Levorotatory - Ability of chiral substances to rotate the plane of polarized light to the left.

c. Specific rotation - The measured angle of rotation of polarized light by a pure chiral sample under

specified standard conditions.

8) Racemic mixture, racemic modification, or racemate - A mixture consisting of equal amounts of

enantiomers. A racemic mixture exhibits no optical activity because the activities of the individual

enantiomers are equal and opposite in value, thereby cancelling each other out.

9) Optical purity - The difference in percent between two enantiomers present in a mixture in unequal amounts.

For example, if a mixture contains 75% of one enantiomer and 25% of the other, the optical purity is 75-25 =

50%.

a. Absolute configuration - A description of the precise 3-dimensional topography of the molecule.

b. Relative configuration - A description of the 3-dimensional topography of the molecule relative to anarbitrary standard. Absolute and relative configurations may or may not coincide.

Stereochemistry 3

The Flying-Wedge projection/ wedge-dot formula)

• The Flying-Wedge projection is themost common three-dimensionalrepresentation of a three dimensionalmolecule on a two dimensional surface(paper). This kind of representation isusually done for molecules containingchiral centre/asymmetric Carbon atom.

• In this representation, the ordinarylines represent bonds in the plane ofthe paper. A solid Wedge ( ) representsa bond above the plane of the paperand a dashed wedge ( ) or a brokenline ( ) represents a bond below theplane of the paper.

Stereochemistry 4

Projection formula It is useful for compounds with 2 or more streogenic/asymmetric centres and Fischer

projection developed 2-dimentional plane projection formulae for 3-dimentional

molecule.

3.Sawhorse formula

2.Newman Projection

1.Fischer Projection

3D Image

Flying-wedge formula

Stereochemistry 5

• It is obtained by projecting the molecule so that Central C-C bond is parallel to the plane of the paper.

• Flat representation of a 3-D molecule.

• A chiral carbon is at the intersection of horizontal and vertical lines.

• Horizontal lines are forward, out of plane.

• More oxidized group is placed at the top of vertical line

• Vertical lines are behind the plane.

• Carbon chain is on the vertical line.

• Highest oxidized carbon is at top.

• Rotation of 180 or 360 in the plane remain unaffected or doesn’t change molecule.

• Rotation of 90 or 270 changes the configuration.

• Any two group interchanges twice

• Three groups rotated at a time clockwise or anticlockwise by keeping 4th group constant.

• Fischer projection formula is restricted only eclipsed form

1.Fischer Projection

Stereochemistry 6

Stereochemistry 7

Fischer Projections

Stereochemistry 8

180° Rotation

• A rotation of 180° is allowed because it will not change the configuration.

Stereochemistry 9

90° Rotation

• A 90° rotation will change the orientation of the horizontal and vertical groups.

• Do not rotate a Fischer projection 90°.

Stereochemistry 10

Glyceraldehyde• The arrow from group 1 to group 2 to group 3 appears counterclockwise

in the Fischer projection. If the molecule is turned over so the hydrogen is in back, the arrow is clockwise, so this is the (R) enantiomer of glyceraldehyde.

Stereochemistry 11

When naming (R) and (S) from

Fischer projections with the

hydrogen on a horizontal bond

(toward you instead of away

from you), just apply the normal

rules backward.

Stereochemistry 12

Fischer Mirror Images

• Fisher projections are easy to draw and make it easier to find enantiomers and internal mirror planes when the molecule has two or more chiral centers.

CH3

H Cl

Cl H

CH3

Fischer (R) and (S)• Lowest priority (usually H) comes forward, so assignment rules are backward!

• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).

• Example:

(S)

(S)

CH3

H Cl

Cl H

CH3

Stereochemistry 13

Summary—Types of isomers

Stereochemistry

Stereochemistry 14

. A Newman projection, useful in alkane stereochemistry, visualizes the conformation of a chemical bond from

front to back, with the front atom represented by a dot and the back carbon as a circle.

Formula can be obtained by projecting the molecule such that the central C-C bond perpendicular to the plane

of paper.

Newman projection –only 2 or more carbon atoms

depict the ‘front’ atom as a dot from which 3 bond radiate, and the ‘back’ or rare carbon atom represented as a

larger circle and 3 bonds radiate from its circumference. The central C-C bond is not visible

The C-C bond in this way, the angle formed between a C-H bond on the front carbon and a C-H bond on the

back carbon is referred to as a dihedral angle

The lowest energy conformation of ethane

all of the dihedral angles are 60o, and the distance

between the front and back C-H bonds is maximized.If we now rotate the front CH3 group 60° clockwise, the

molecule is in the highest energy and the dihedral angles are all 0o

Stereochemistry 15

The energy of the eclipsed conformation, where the

electrons in the front and back C-H bonds are closer

together, is approximately 12 kJ/mol higher than that of

the staggered conformation.

Another 60° rotation returns the molecule to a second

staggered conformation. This process can be continued

all around the 360° circle, with three possible eclipsed

conformations and three staggered conformations, in

addition to an infinite number of conformations in

between these two extremes.

Newman projection

Stereochemistry 16

Stereochemistry 17

Stereochemistry 18

Stereochemistry 19

Fischer projection formula into sawhorse formula :horizontal bonds are above the plane and terminal vertical bonds are below the plane. The center C-C written in slanting manner .The Fischer projection formula is represents only in eclipsed form

Stereochemistry 20

ii)Sawhorse- eclipsed and staggered Sawhorse projection into Newman projection formula :- First circle is drawnwhich represents the carbon atom at the backside and the centre of the circle representsthe front carbon atom. Therefore the bonds attached to the front carbon atoms are joinedto the center of the circle whereas the bonds attached to the backside carbon atom arejoined only to the circumference of the circle.

Stereochemistry 21

.

Three stereoisomers of 2,3-dichlorobutane

The structure of 2,3-dichlorobutane is CH3*CHCl*CHClCH3

The two carbon atoms marked with blue asterisks are chiral centers.

The maximum number of stereoisomers is 2n, where n is the number of chiral

centers.

Since n=2, the maximum number of stereoisomers is 22=4.

Stereoisomers of 2,3-dichlorobutane

Structures 1 and 2 are two different

nonsuperimposable mirror images of each other.

But Structures 3 and 4 are meso compounds.

They are superimposable on each other, so they are

the same compound.

So, there are only three stereoisomers of 2,3-

dichlorobutane.

Stereochemistry 22

Stereochemistry of Carbon compound containing two similar asymmetric carbon atoms

• If 3 groups on asymmetric carbon atoms are same then they are similar asymmetric carbon atoms e.gHOOC-*CH(OH)*CH(OH)COOH 2n n= 2

Stereochemistry 23

Characteristic of meso compounds

• Due to internal compensation meso isomers are optically inactive

• It possesses a plane of symmetry

• It is one which is superimposable on its mirror image

• All diasteroisomers are called meso forms

• The physical properties of the meso forms are different than d &l forms e.g Tartaric acid

Stereochemistry 24

(+)-tartaric acid: [α]D = +13º m.p. 172 ºC

(–)-tartaric acid: [α]D = –13º m.p. 172 ºC

meso-tartaric

acid:[α]D = 0º m.p. 140 ºC

Configuration and relative • e.g Tartaric acid - Two of these stereoisomers are enantiomers and the third is an

achiral diastereomer, called a meso compound. Meso compounds are achiral (optically inactive) diastereomers of chiral stereoisomers.

Stereochemistry 25

1. Chemical reaction without displacement at thechiral centre concerned

2. Chemical reaction without displacement3. X-ray analysis4. Asymmetric inductive correlation5. Optical rotation (a) monochromatic rotation (b)

Rotatory dispersion6. The study of quasi-racemic compound7. Enzyme studies.8. A Reaction does not involve the breaking of bond

to a chiral proceeds with retention ofconfiguration about that chiral centre.

Oxidation of (+)-glyceraldehyde (1) with HgO gives(−)- glyceric acid(2), a reaction that does not alter the stereocenter.Thus the absolute configuration of (−)-glyceric acidmust be the same as that of (+)-glyceraldehyde. HNO2 oxidation of (+)- isoserine(3) gives (–)-glyceric acid, establishing that (+)-isoserine also has the same absolute configuration.(+)-Isoserine can be converted by a 2-stage processof bromination and ZN reduction to give (–)-lacticacid, therefore (–)-lactic acid also has the sameabsolute configuration. If a reaction gave theenantiomer of a known configuration, as indicatedby the opposite sign of optical rotation, it wouldindicate that the absolute configuration is inverted.

Stereochemistry 26

Absolute configuration

If, in the Fischer projection, like ligands are on the same side of the bond linking the chiral centers, the

compound is identified as the erythro isomer; if they are on the opposite sides, the compound is identified as

the threo isomer.

Stereochemistry 27

Two older prefixes still commonly used to distinguish diastereomers are threo and erythro. In the case of saccharides, when drawn in the Fischer projection the erythro isomer has two identical substituents on the same side and the threo isomer has them on opposite sides.

Erythro isomer and threo isomer nomenclature

Stereochemistry 28

Stereochemistry 29

(+)- and (−)- or d- and l- nomenclature

An enantiomer can be named by the direction in which it rotates the plane of polarized light. If it rotates the light

clockwise that enantiomer is labeled (+). Its mirror-image is labeled (−). The (+) and (−) isomers have also been termed d- and l-. (dextrorotatory and levorotatory)

d-glyceraldehyde

(R)-glyceraldehyde

(+)-glyceraldehyde

l-glyceraldehyde

(S)-glyceraldehyde

(−)-glyceraldehyde

Projection Formulae Inter-conversion

Fischer Projection Newman Projection

Fischer projection refers to eclipsed conformation

Stereochemistry 30

Stereoisomerism

• The dimension of a molecule can be interpreted topologically, based on the connections of the consisting atoms, or spatially, based on the Cartesian coordinates of them. In this section the notion of dimension is used in spatial sense.

• Molecules with same connectivity but different spatial arrangement are called stereoisomers.

Stereochemistry 31

Stereochemistry 32

33

Determining the relationship between two nonidentical molecules

Stereochemistry

Stereochemistry

Geometric isomerism

• Geometric isomerism (also known as cis-transisomerism or E-Z isomerism) is a form of stereoisomerism.

• Geometric isomers have the same structural formulas but differ inthe arrangement of groups at a single atom, at double bonds, or inrings and it is because of molecular symmetry. These compound donot rotate the plane polarised light.

• Unsaturated compound and cyclic compounds exhibit geometricalisomerism.

Stereochemistry 34

Cis isomers -Similar gr on same side

Trans isomers- Similar gr on opposite side

Stereochemistry 35

Stereochemistry 36

Stereochemistry 37

38

• The chemical and physical properties of two enantiomers are identical except

in their interaction with chiral substances.

• The physical property that differs is the behavior when subjected to plane-

polarized light ( this physical property is often called an optical property).

• Plane-polarized (polarized) light is light that has an electric vector that

oscillates in a single plane.

• Plane-polarized light arises from passing ordinary light through a polarizer.

• Originally a natural polarizer, calcite or iceland spar, was used. Today,

polarimeters use a polarized lens similar to that used in some sunglasses.

• A polarizer has a very uniform arrangement of molecules such that only

those light rays of white light (which is diffuse) that are in the same plane as

the polarizer molecules are able to pass through.

• A polarimeter is an instrument that allows polarized light to travel through a

sample tube containing an organic compound and permits measurement of

the degree to which the light is rotated.Stereochemistry

Optical Activity

• With achiral compounds, the light that exits the sample tube remains

unchanged. A compound that does not change the plane of polarized light

is said to be optically inactive.

Optical Activity

Stereochemistry 39

40

• With chiral compounds, the plane of the polarized light is rotated through an

angle . The angle is measured in degrees (°), and is called the observed

rotation. A compound that rotates polarized light is said to be optically active.

Stereochemistry

Optical Activity

41

• The rotation of polarized light can be clockwise or counterclockwise.

• If the rotation is clockwise (to the right of the noon position), the

compound is called dextrorotatory. The rotation is labeled d or (+).

• If the rotation is counterclockwise, (to the left of noon), the compound is

called levorotatory. The rotation is labeled l or (-).

• Two enantiomers rotate plane-polarized light to an equal extent but in

opposite directions. Thus, if enantiomer A rotates polarized light +5°, the

same concentration of enantiomer B rotates it –5°.

• No relationship exists between R and S prefixes and the (+) and (-)

designations that indicate optical rotation.

Optical Activity

Stereochemistry

Optical Families

42

D-(+)-glyceraldehyde L-(-)-glyceraldehyde

CHO

OHH

CH2OH

CHO

HO H

CH2OH

* *

CHO CHO

(CHOH)n

OHH

CH2OH

*

(CHOH)n

HO H

CH2OH

D-sugars L-sugars

CO2H

NH2H

R

CO2H

H2N H

R

D-amino acids L-amino acids

Stereochemistry

Distinguish between geometrical isomerism and optical isomerism

• Geometrical

• C=C bonds have restricted rotation so the groups

on either end of the bond are ‘frozen’ in one

position; it isn’t easy to flip between the two.

• This produces two possibilities. The two structures

cannot interchange easily so the atoms in the two

molecules occupy different positions in space.

• Geometric isomers have the same structural

formulas but differ in the spatial arrangement of

groups at a single atom, at double bonds, or in rings

• It is having two forms cis and trans and E

(entagegen)/Z Zussamen

• Optical

• occurs when compounds have non-superimposable mirror images Isomers thetwo different forms are known as opticalisomers or enantiomers.

• Optical isomers have the same structuralformulas but differ in the configuration &because of their molecular asymmetry thesecompound rotate the plane of planepolarised light.

• Light appears in D (dextrorotatory) /L(laevorotatory )

Stereochemistry 43

44

• An equal amount of two enantiomers is called a racemic mixture or a racemate.

A racemic mixture is optically inactive. Because two enantiomers rotate plane-

polarized light to an equal extent but in opposite directions, the rotations cancel,

and no rotation is observed.

Racemic Mixtures

Stereochemistry

45

• Specific rotation is a standardized physical constant for the amount that a

chiral compound rotates plane-polarized light. Specific rotation is denoted by

the symbol [] and defined using a specific sample tube length (l, in dm),

concentration (c in g/mL), temperature (250C) and wavelength (589 nm).

Racemic Mixtures

Stereochemistry

46

• Enantiomeric excess (ee) is a measurement of the

excess of one enantiomer over the racemic mixture.

Enantiomeric excess and Optical purity: ee and op

ee = % of one enantiomer - % of the other enantiomer.

• Consider the following example: If a mixture contains 75% of one

enantiomer and 25% of the other, the enantiomeric excess is 75% - 25% =

50%. Thus, there is a 50% excess of one enantiomer over the racemic

mixture.

• ee is numerically equal to Optical Purity.

• The optical purity can be calculated if the specific rotation [] of a mixture

and the specific rotation [] of a pure enantiomer are known.

op = ([] mixture/[] pure enantiomer) x 100.Stereochemistry

47

• Since enantiomers have identical physical properties, they cannot be separated by

common physical techniques like distillation.

• Diastereomers and constitutional isomers have different physical properties, and

therefore can be separated by common physical techniques.

Physical Properties of Stereoisomers: e.g Tartaric acid

The physical

properties of the three

stereoisomers of tartaric

acid.

Stereochemistry

48

• Two enantiomers have exactly the same chemical properties except for their

reaction with chiral non-racemic reagents.

• Many drugs are chiral and often must react with a chiral receptor or chiral enzyme

to be effective. One enantiomer of a drug may effectively treat a disease whereas

its mirror image may be ineffective or toxic.

Chemical Properties of Enantiomers:

Stereochemistry

Chirality or Dissymmetry • Chirality is a geometric property of some molecules and ions or object

in the universe. A chiral molecule/ion is non-superposable on its mirror image. The presence of an asymmetric carbon center is one of several structural features that induce chirality in organic and inorganic molecules.

(S)-(+)-lactic acid (left) and (R)-(–)-lactic acid (right) are

nonsuperimposable mirror images of each other

Stereochemistry 49

FISCHER PROJECTION OF MESO-TARTARIC ACID

A meso compound or meso isomer is a stereoisomer with an identical or superposable mirror

image

Most compounds that contain one or more asymmetric carbon atoms show enantiomerism, but this is not

always true. There are a few known compounds that do have asymmetric carbon atoms, but, being non-

dissymmetric with respect to the whole molecule, do not show enantiomerism. Thus, meso tartaric acid has

two asymmetric carbon atoms, but samples still exhibit optical inactivity because each of the two halves of the

molecule is equal and opposite to the other and thus is superposable on its geometric mirror.

d-(-)-Tartaric Acid is an isomer that makes up Racemic acid. It

is also called levotartaric acid, with levotartaric (-) coming from

the word levorotatory, meaning that the substance rotates the

plane of polarized light counterclockwise, or to the left

l-(+)-Tartaric Acid (dextrotartaric acid) is the other

isomer that makes up Racemic acid. Part of its name,

dextrotartaric comes from the word dextrorotatory (+),

meaning that it rotates the plane of polarized light

clockwise, or to the right

(+)and (-)Tartaric Acid optically active

Meso Tartaric acid Optically inactive

Stereochemistry 50

Stereochemistry of Carbon compound with one asymmetric atom

• An asymmetric carbon atom (chiral carbon) is a carbon atom that is attached to four different types of atoms or groups of atoms.

• If n is the number of asymmetric carbon atoms then the maximum number of isomers = 2n

Stereochemistry 51

ENANTIOMERS AND DIASTEREOMERS

Rotating structure ( b) 180° in the plane of the paper, the only allowable rotation, does notlead to a form that is superimposable on structure ( a). Rotations of less than or more than180° are not allowed because in a two‐dimensional projection, it is impossible to see thedifference in the position of atoms that are located in front of or behind the plane.

A Fischer projection is the most useful projection for discovering enantiomers. Compare the 2‐chlorobutane enantiomer

Stereochemistry 52

Optical Families

D-(+)-glyceraldehyde L-(-)-glyceraldehyde

CHO

53

OHH

CH2OH

CHO

HO H

CH2OH

* *

(CHOH)n

OHH

CH2OH

*

CHO

(CHOH)n

HO H

CH2OH

CHO

CO2H

NH2H

R

CO2H

H2N H

R

D-sugars L-sugars

D-amino acids L-amino acids

Stereochemistry

Distinction between enantiomers and diastereomersEnantiomers• Enantiomers are optical isomers that are non-

superimposable mirror images of each other.

• Organic compounds containing a chiral carbonthat have the same structural as well aschemical formula but are non-superimposableon each other and are mirror images of eachother, are nothing but enantiomers.

• One chiral C atom can have enantiomers

• ll the stereocenters (chiral carbons) of onestereoisomer differs in orientation from thestereocenters of the other stereoisomer.

• 2-bromo-3-chloro-butane

Diastereoisomers• Diastereomers are stereoisomers that are non-

superimposable, non-mirror images of each other.

• Organic compounds with two or more chiral carbonthat have the same structural and molecularformula; these compounds are, however, non-superimposable and non-mirror images of eachother.

• At least 2 Chiral carbon atoms to showdiastereomers.

• only some stereocenters (chiral carbons) of onestereoisomer differs in orientation from thestereocenters of the other stereoisomer

Stereochemistry 54

Enantiomers

• Enantiomers of a compound have thesame physical properties except opticalactivity, but differ in chemical properties.

• A compound with one or morestereocenters (chiral carbons) is capableof enantiomerism (property to formenantiomers).

• All enantiomers show optical activity.When they rotate light in the clockwisedirection, they are known as dextrorotary,(+) or d, and when they rotate light in theanticlockwise direction, they are knownas levorotary, (-) or l. When a compoundcontains equal number of d and lmolecules, they render the compoundoptically inactive and are called a race

mixture.

Diastereoisomers

• Diastereomers of a compound differ intheir physical as well as chemicalproperties.

• A compound needs at least twostereocenters (chiral carbons) in order toform diastereomers.

• Not all diastereomers are optically active.Some stereoisomers are said to be mesocompounds and seem to be opticallyinactive despite having two or more chiralcarbons. The compounds possess a line ofsymmetry, meaning, one half of thecompound is identical to the other half,but these two halves differ in theirorientation (if one half has S configurationthen the other half has R configuration).

Stereochemistry 55

2E-2,3-dichlorobut-2-ene 2Z-2,3-dichlorobut-2-ene

E/Z notation

The cis/trans system for naming isomers is not effective if more than two different

substituents are attached to the double bond. In this case, following the Cahn-Ingold-

Prelog priority rules a priority is assigned to each substituent on a double bond. If the

two groups of higher priority are on opposite sides of the double bond

(trans arrangement), then the E configuration is assigned to the bond. If the two groups

of higher priority are on the same side of the double bond (cis arrangement), than

the Z configuration is assigned to it.

Stereochemistry 56

Conversion rule

Stereochemistry 57

Conversion rule – e.g 1,2-dichloro propane with single stereogenic centre at C2

Stereochemistry 58

(R) and (S) notation for Fischer formulae.g D(-)2-Amino propionic acid

Stereochemistry 59

(R) and (S) notation for Fischer formula

Stereochemistry 60

Sequence at C2: OH, COOH, Y, H

Molecule with two chiral centres :

When molecule contain two chiral centers , each chiral center is consider separately. By using r/s notation assigned

each centre e.g Tartaric acid chiral centers are C2 and C3

Stereochemistry 61

Stereochemistry 62

Cahn-Ingold-Prelog priority rules• Since enantiomers are different configurations of the same compound, a notational system had

to be developed that would indicate the 3‐dimensional arrangement of atoms at specific

stereogenic centers. Such a system was devised by the chemists Cahn, Ingold, and Prelog. In

this system, the substituents of a stereogenic center are ranked by atomic weight as dictated by

a series of priority rules.

• A projection of the molecule is then viewed so that the group or atom of lowest priority is

eclipsed by the stereogenic center. The ranking of the three remaining groups is then

determined.

• If their rank from highest to lowest is in a clockwise direction, the configuration is R.

• if the rank declines in a counterclockwise direction, the configuration is S.

• The labels R and S come from the Latin words rectus, which means “right,” and sinister,

meaning “left.” The right and left designations refer only to the order of atoms or groups about

a stereogenic center. They do not refer to the direction in which plane‐polarized light is rotated

by the molecule.Stereochemistry 63

Sequence rules

1. Identify the four different atoms or groups attached to the stereogenic center.

2. The two possible spatial arrangements are called configurations.

3. Rank the atoms or groups based on the priority rules (see the list following this

one).

4. Orient a projection of the molecule in space so that the group or atom of lowest

rank is eclipsed by the stereogenic center.

5. Determine the ranking of the remaining visible atoms or groups.

6. Each asymmetric carbon atom is assigned a letter (R) or (S) based on its three-

dimensional configuration.

7. If the ranking declines in a clockwise direction, the configuration is R; if the

ranking declines in a counterclockwise direction, the configuration is S.

Stereochemistry 64

Assign a relative “priority” to each group bonded to the asymmetric carbon. Group 1 would have the highest priority, group 2 second, etc.Atoms with higher atomic numbers receive higher priorities.

I > Br > Cl > S > F > O > N > 13C > 12C > 2H > 1H

Stereochemistry 65

Sequence rules

3. If a group contains multiple bonds, the doubly or triply bonded atoms are counted as two or three of

those atoms, respectively. Thus the carbonyl group

is considered to have two carbon‐oxygen bonds, one actual and one theoretical

A cyano group

is considered to have three carbon‐nitrogen bonds, one actual and two

theoretical. For comparison purposes, an actual bond ranks higher than a

theoretical bond of the same type. For example, when ranking the cyano group

against

The priority rules rank atoms and groups based on atomic mass

1. For the four atoms directly attached to the stereogenic center, the higher the atomic mass, the higher

the rank.

2. If two or more atoms directly attached to the stereogenic center have the same mass, work outward

along the chains of the groups they are in, atom by atom, until a point of difference is reached. The rank

is assigned at this point of difference, based on the difference in atomic mass.

O C

(O)

O (C)

C C

(C)

C (C)

Stereochemistry 66

Sequence rules

Assign Priorities-1. Ligands of higher atomic number get higherpriority than ligands of lower atomic numbers

Atomic number: F > N > C > H

C

Cl

H

FBr H

1 Br

2Cl

F 3

C

Cl

H

BrF H

Br1

2Cl

3F

= =

1-2-3: clockwise :R counterclockwise : S

One interchange!

C

CH2CH3

H

CH2OHH3CH

CH2OH

1

2CH2CH3

H3C

3

=

2. In case of equal finish, use

the next atom along the chain

and use rule no. 1

counterclockwise : SStereochemistry 67

Sequence rules

Stereochemistry 68

Sequence rules

Stereochemistry 69

Sequence rules

Stereochemistry 70

Sequence rules

(R) and (S) Configuration: Breaking Ties

In case of ties, use the next atoms along the chain of each group as tiebreakers.

71Stereochemistry

(R) and (S) Configuration: Rule 4 - Multiple Bonds

Treat double and triple bonds as if each were a bond to a separate atom.

Stereochemistry 72

Stereochemistry 73

(R) and (S) Configuration: Step 2

• Working in 3-D, rotate the molecule so that the lowest priority group is in back.

• Draw an arrow from highest (1) to second highest (2) to lowest (3) priority group.

• Clockwise = (R), Counterclockwise = (S)

74Stereochemistry

Assign Priorities

Draw an arrow from Group 1 to Group 2 to Group 3 and

back to Group 1. Ignore Group 4.

Clockwise = (R) and Counterclockwise = (S)

Counterclockwise

(S)

75Stereochemistry

Example

C

OH

CH3CH2CH2

H

CH2CH3

1

23

4

C

CH2CH3

CH3CH2CH2

OH

H

1

2

3

4

rotate

When rotating to put the lowest priority group in the back,

keep one group in place and rotate the other three.

Clockwise

(R)

76Stereochemistry

Example (Continued)

CH3

CH3CH2CH=CH

CH2CH2CH2CH3

H1

2

3

4

Counterclockwise

(S)

77Stereochemistry

Conformational Analysis

• Arrangement in space of atoms of a molecule which can arise by rotation about a single bond and is capable of definite existence. It is obtained b single bond are called as conformations or conformer or rotational isomers.

Stereochemistry 78

Conformational Analysis Ethane-Staggered is more stable because all H atoms of carbon atoms are directly opposite to or eclipsed by vicinal H atoms on the carbon atoms The conformation known as eclipsed form. H atoms Distance is closed hence having higher energy than staggered. If rotate front C at 300 both conformations obtained thrice. Free rotation at 60 , 180 ,300 maxima and 120 , 240 ,360 is minima and all forms are having same energy.

Stereochemistry 79

• Butane (CH3CH2CH2CH3) has four tetrahedral carbons and three carbon-carbonbonds connecting them together. Staggered is most stable conformation-clockwise and anticlockwise rotation gives eclipsed due to repulsive interactionbetween eclipsed H atom and ethyl gr. At 360 both confirmation produced inthrice.

a) Two Confirmation of n-butane rotation at C1-C2

Staggered

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b) Six Confirmation of n-butane rotation at C2-C3

with its four-carbon chain. There are now three rotating carbon-carbon single bonds to consider, but we will focus on the middle bond between C2 and C3. above are two representations of butane in a conformation which puts the two CH3 groups (C1 and C4) in the eclipsed position, with the two C-C bonds at a 0o dihedral angle.

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• If we rotate the front, (blue) carbon by 60° clockwise, the butane molecule is now in a staggered conformation.

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• This is more specifically referred to as the gauche conformation ofbutane. Notice that although they are staggered, the two methyl groupsare not as far apart as they could possibly be.

• A further rotation of 60° gives us a second eclipsed conformation (B) inwhich both methyl groups are lined up with hydrogen atoms.

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• One more 60 rotation produces anotherstaggered conformation called the antiplanarconformation, where the two methyl groupsare positioned opposite each other (adihedral angle of 180o).

Because the anti conformation is lowest in

energy (and also simply for ease of

drawing), it is conventional to draw open-

chain alkanes in a 'zigzag' form, which

implies anti conformation at all carbon-

carbon bonds

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Relative energies for the various eclipsed, staggered, and gauche conformations.

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Sumup for C2-C3

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