Isomerism Molecules with same molecular formula but diff arrangement of atom

Two types of Isomerism

Positional Chain Isomer Functional Gp Isomer

C – C – C – C – OH

C4H10O1

Structural Isomerism

• Same molecular formula • Diff structural formula • Diff arrangement of atom

Diff hydrocarbon chain skeleton

• Same molecular formula • Same structural formula/ same connectivity • Diff spatial arrangement of atom

Stereoisomerism

Hydrocarbon Chain Isomer

Diff functional gp position Diff functional gp

C – C – C – OH

׀

CH3

C – C – C –C

׀

OH

C – C – C – C

׀

OH

C – C – C – C

׀

OH

C – C – C – O – C

Optical Isomer Geometric Isomer

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Compound Ethane Ethanoic acid

Empirical formula CH3 CH2O

Molecular formula C2H6 C2H4O2

Full SF

Condensed SF CH3CH3 CH3COOH

Stereochemical formula

(3D)

Isomer Physical property

Chemical property

Structural isomer - Hydrocarbon chain - Functional gp position - Functional gp

Different Different Different

Similar Similar

Different

Geometrical isomer Different Similar

Optical isomer Similar Similar

H H

׀ ׀

H - C – C – H

׀ ׀

H H

H O

‖ ׀

H - C - C - OH

׀

H

Structural formula – arrangement atoms in molecule (2/3D)

H H

׀ ׀

H - C – C – H

׀ ׀

H H

CH3CH3

ethane

Display full SF Condensed SF Ball/stick model Spacefilling

Click here chemical search.

same connectivity but diff spatial arrangement

CI

Isomerism

Two types of Isomerism

Positional Chain Isomer

Functional Gp Isomer

C4H10O1

Structural Isomerism

• Same molecular formula • Diff structural formula • Diff arrangement of atom

• Same molecular formula • Same structural formula/same connectivity

• Diff spatial arrangement of atom

Stereoisomerism

Hydrocarbon Chain Isomer

Optical Isomer Geometric Isomer

Requirement for geometric isomers • Presence of C=C double bond - prevent bond rotation • Presence of ring structure - prevent bond rotation • Carbon atom in double bond bonded to diff atom

Cis Isomers Atom located on same side

Trans Isomers Atom located on diff side

Presence C=C Presence of ring structure

CI CI

׀ ׀

C = C

׀ ׀

H H

Cis 1, 2 dichloroethene

CI H

׀ ׀

C = C

׀ ׀

H CI

Trans 1, 2 dichloroethene

Cis 1, 2 dichlorocyclopropane Trans 1, 2 dichlorocyclopropane

Carbon atom bond to diff atom

double bond

C – C – C – C – OH C – C – C –C

׀

OH

C – C – C – O – C

C – C – C – OH

׀

CH3

CI CI CI

CI

H

H H H

CI CI

H H

H

H

CI

Cis 1, 3 dichlorocyclobutane Trans 1, 3 dichlorocyclobutane

same atom

different atom χ

✓

No geometric isomers

Geometric isomers

same connectivity but diff spatial arrangement

• Same molecular formula • Same structural formula/same connectivity

• Diff spatial arrangement of atom

Stereoisomerism

Geometric Isomer

Requirement for geometric isomers • Presence of C=C double bond - prevent bond rotation • Presence of ring structure - prevent bond rotation • Carbon atom in double bond bond to diff atom

Cis Isomers Atom located on same side

Trans Isomers Atom located on diff side

Presence C=C Presence of ring structure

CI CI

׀ ׀

C = C

׀ ׀

H H

Cis 1, 2 dichloroethene

CI H

׀ ׀

C = C

׀ ׀

H CI

Trans 1, 2 dichloroethene Cis 1, 2 dichlorocyclopropane Trans 1, 2 dichlorocyclopropane

Carbon atom bond to diff atom

double bond

CI CI CI

CI

H

H H H

same atom

different atom

Cis / Trans naming sys

click here E/Z naming system

2 diff substituent on each carbon

[Z] 1, 2 dichloroethene [E] 1, 2 dichloroethene

CI CI

׀ ׀

C = C

׀ ׀

H H

CI H

׀ ׀

C = C

׀ ׀

H CI

Atom same side Atom opposite side

[Z] 1, 2 dichlorocyclopropane [E] 1, 2 dichlorocyclopropane

E / Z naming sys

E/Z (CIP priority) 4 diff substituents

1

1 – high priority 2 – low priority

1

2

1

2 2

2

1

Priority same side – Z Priority opp side - E

H H

CI CI 1 1

2 2 H CI

CI H

1

1 2

2

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

E/Z naming system ↓

Cahn-Ingold-Prelog (CIP)

CH3 H

׀ ׀

C = C

׀ ׀

Br OH

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

1

2

1

2 C atomic mass ↓

Br atomic mass ↑

O atomic mass ↑

H atomic mass ↓

Priority same side - Z

same atom

different atom

Cis / Trans naming sys

click here E/Z naming system

2 diff substituent on each carbon

[Z] 1, 2 dichloroethene [E] 1, 2 dichloroethene

CI CI

׀ ׀

C = C

׀ ׀

H H

CI H

׀ ׀

C = C

׀ ׀

H CI

[Z] 1, 2 dichlorocyclopropane [E] 1, 2 dichlorocyclopropane

E / Z naming sys

E/Z (CIP priority) 4 diff substituents

1

1 – high priority 2 – low priority

1

2

1

2 2

2

1

Priority same side – Z Priority opp side - E

H H

CI CI 1 1

2 2 H CI

CI H

1

1 2

2

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

E/Z naming system Cahn-Ingold-Prelog (CIP)

CH3 H

׀ ׀

C = C

׀ ׀

Br OH

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

1

2

1

2 C atomic mass ↓

Br atomic mass ↑

O atomic mass ↑

H atomic mass ↓

Priority same side - Z

CI I

׀ ׀

C = C

׀ ׀

H Br

CH3 CH3

׀ ׀

C = C

׀ ׀

H CI

[E] 2-chlorobut-2-ene

Cis 2 chlorobut-2-ene

[Z] 2-bromo-1-chloro-2-iodoethene

CI Br

׀ ׀

C = C

׀ ׀

H I

[E] 2-bromo-1-chloro-2-iodoethene

Br atomic mass ↓

H atomic mass ↓

I atomic mass ↑

2 2

1 1

CI atomic mass ↑

CI atomic mass ↑

I atomic mass ↑

Br atomic mass ↓

1

1

2

2

H atomic mass ↓

CH3 CI

׀ ׀

C = C

׀ ׀

H CH3

[Z] 2-chlorobut-2-ene

Trans 2 chlorobut-2-ene

based on atomic mass

1 1

2 2 1

1 2

2

CH3 CH3

׀ ׀

C = C

׀ ׀

H C2H5

Br CH3

׀ ׀

C = C

׀ ׀

H C2H5

H CH3

׀ ׀

C = C

׀ ׀

Br C2H5

CH3 H

׀ ׀

C = C

׀ ׀

Br OH

1

1 2

2 1 1

2 2

E/Z naming system Cahn-Ingold-Prelog (CIP)

H COOH

׀ ׀

C = C

׀ ׀

HOOC H

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

1

1

2

2

H atomic mass ↓

C atomic mass ↑

C atomic mass ↑

H atomic mass ↓

Br H

׀ ׀

C = C

׀ ׀

CH3 OH

H atomic mass ↓

C atomic mass ↓

O atomic mass ↑ 1 1

2 2

Br atomic mass ↑

Br atomic mass ↑

O atomic mass ↑

H atomic mass ↓

1 2

2

C atomic mass ↓

based on atomic mass

2

1 1

2

1

1 2

2

1

E - Priority opposite side Z - Priority same side E - Priority opposite side

Trans but-2-ene-1,4-dioic acid

[Z] 1-bromo-2-methylbut-1-ene

Br atomic mass ↑

H atomic mass ↓

H H ׀ ׀ C – C – H ׀ ׀ H H

H ׀ C – H ׀ H

[E] 1-bromo-2-methylbut-1-ene

Br atomic mass ↑

H atomic mass ↓

H H ׀ ׀ C – C – H ׀ ׀ H H

C – bond H, H, C (Higher priority)

H ׀ C – H ׀ H

C – bond H, H, H (Lower priority)

[E] 3-methylpent-2-ene

C atomic mass ↑

H atomic mass ↓

H H ׀ ׀ C – C – H ׀ ׀ H H

C – bond H, H, C (Higher priority)

C – bond H, H, C (Higher priority)

C – bond H, H, H (Lower priority)

C – bond H, H, H (Lower priority)

H ׀ C – H ׀ H

[Z] 3-methylpent-2-ene

H CH3

׀ ׀

C = C

׀ ׀

CH3 C2H5

H atomic mass ↓

C atomic mass ↑

H H ׀ ׀ C – C – H ׀ ׀ H H

H ׀ C – H ׀ H

C – bond H, H, C (Higher priority)

C – bond H, H, H (Lower priority)

CH3 H

׀ ׀

C = C

׀ ׀

H C2H5

CH3 CH2OH ׀ ׀

C = C

׀ ׀ CH3CH2 CHO

Br CH2OH

׀ ׀

C = C

׀ ׀

CI CHO

CI CH2OH

׀ ׀

C = C

׀ ׀

Br CHO

CH3 H

׀ ׀

C = C

׀ ׀

Br OH

1

2 2

1

E/Z naming system Cahn-Ingold-Prelog (CIP)

H COOH

׀ ׀

C = C

׀ ׀

HOOC H

1 – high priority 2 – low priority

Priority same side – Z Priority opp side - E

1

1

2

2

H atomic mass ↓

C atomic mass ↑

C atomic mass ↑

H atomic mass ↓

Br H

׀ ׀

C = C

׀ ׀

CH3 OH

H atomic mass ↓

C atomic mass ↓

O atomic mass ↑ 1 1

2 2

Br atomic mass ↑

Br atomic mass ↑

O atomic mass ↑

H atomic mass ↓

1 2

2

C atomic mass ↓

based on atomic mass

2

1 1

2

1

1 2

2

1

E - Priority opposite side Z - Priority same side E - Priority opposite side

Trans but-2-ene-1,4-dioic acid

Br atomic mass ↑

CI atomic mass ↓

H ׀ C = O

H ׀ C – H ׀ OH

Br atomic mass ↑

CI atomic mass ↓

C – bond H, O, O (Higher priority)

H ׀ C – OH ׀ H

C – bond H, O, O (Higher priority)

C – bond H, O, O (Higher priority)

C – bond H, O, H (Lower priority)

C – bond H, O, H (Lower priority)

H ׀ C = O

H H ׀ ׀ H – C – C ׀ ׀ H H

H ׀ H – C ׀ H

C – bond H, H, H (Lower priority)

Z - Priority same side

H ׀ C = O

H ׀ C – H ׀ OH

C – bond H, O, H (Lower priority)

E - Priority opposite side

C – bond H, H, C (Higher priority)

Z - Priority same side

Pent – 2-ene 2,3-dichlorobut-2-ene

H H

׀ ׀

C = C

׀ ׀

CH3 C2H5

[E]-2,3 dichloro

but-2-ene

CI CI

׀ ׀

C = C

׀ ׀

CH3 CH3

CH3 CI

׀ ׀

C = C

׀ ׀

CI CH3

2 2 2

2

2

2 2 2 1 1

1

1

1

1

1 1

[Z] pent-2-ene [E] pent-2-ene [Z]-2,3 dichloro

but-2-ene

Draw and name isomers using E/Z convention

Draw structural formula isomer with MF below, state type of isomerism

Stereoisomerism

C2 H2 CI2

CI CI

׀ ׀

C = C

׀ ׀

H H

CI H

׀ ׀

C = C

׀ ׀

CI H

Both Structural formula

Geometric Isomer

CI CI

׀ ׀

C = C

׀ ׀

H H

CI H

׀ ׀

C = C

׀ ׀

H CI

Cis 1, 2 dichloroethene Trans 1, 2 dichloroethene

[Z] 1, 2 dichloroethene [E] 1, 2 dichloroethene

2 2

1 1

2

2

1

1

C3H4CI2

CI

CI

CI CI

H H H

H Both Structural

formula

CI CI CI

Geometric

Isomer

H H H CI

H

Cis 1, 2 dichlorocyclo

propane

Trans 1, 2 dichlorocyclo

propane

[Z] 1, 2 dichlorocyclo

propane

[E] 1, 2 dichlorocyclo

propane

Which exhibit cis/trans isomerism ?

CI H

׀ ׀

C = C

׀ ׀

Br H

F CH3

׀ ׀

C = C

׀ ׀

H CI

F CH3

׀ ׀

C = C

׀ ׀

CI CH3

CH3CH=CHCH3 CH3CH=CH2

CH(F)=C(CH3)2 CH(CI)=C(CI)CH3

Draw geometric isomers

CH3CH=CHCH2CH3

FCH = CHF

Which is structural isomer CH3COCH2CH3

H H

׀ ׀

C = C

׀ ׀

CH3 C2H5

CH3 H

׀ ׀

C = C

׀ ׀

H C2H5

F F

׀ ׀

C = C

׀ ׀

H H

F H

׀ ׀

C = C

׀ ׀

H F

Which exhibit cis/trans isomerism ?

CH3CH=CHCH2CH3

FCH = CHF

Cis/ [Z] Cis/ [Z] Trans / [E] Trans / [E]

CH3CH2-O-CH2CH3 CH3CH2CH2-CH

‖

O

CH2=CH-CH-CH3

׀

OH

Geometric Isomers Optical Isomers

Same chemical property– Same functional gp • Diff physical property – Diff spatial arrangement

(Diff density, solubility, melting pt/boiling pt)

• Same chemical property – Same functional gp • Same physical property

(Same density, solubility, melting pt/boiling pt)

Vs

Enantiomer Mirror image of each other

Enantiomer Mirror image of each other

Stereoisomerism

Molecules with same molecular formula but diff spatial arrangement

• Same molecular formula • Same structural formula / same connectivity

• Diff spatial arrangement of atom

Cis Isomer Atom on same side

Trans Isomer Atom on diff side

click here for optical rotation sugar click here for polarimeter

click here opical rotation corn syrup click here polarimeter Pasco Demo

Mirror image

Right handed Left handed

Non superimposable

Chiral/asymmetrical/stereocentre carbon (4 diff groups)

same connectivity but

diff spatial arrangement

Isomers with same Molecular Formula and Structural Formula but diff spatial arrangement

• At least 1 asymmetric / chiral carbon / stereocentre , bonded to 4 diff gp

• NH2CH(R)COOH show optical isomerism

• Optical isomers/mirror images call enantiomers (cannot superimpose on each other)

• Similar physical and chemical property except for the effect on rotation of plane of polarised light

• Optically active – enantiomer rotate plane polarised light to one direction (clockwise / anticlockwise)

• Optically inactive – enantiomer present in equal amt (equimolar) – racemic mix and rotation cancel out each other

Optical Isomers

chiral carbon – 4 diff gp

Optically inactive – Rotation cancel out each other

Enantiomer (R) - rotate clockwise Enantiomer (S) – rotate anticlock wise

50% 50% 70% 30%

Optically active – Net Rotation clockwise

Non superimposable

Non superimposable

1. Light pass through 1st polariser – plane polarised light produced

2. Sample introduce to tube. Sample is optically active

Rotate plane of polarised light to one direction

3. Turn analyzer either clockwise/anticlock wise to give light of max intensity again

4. If sample rotate light 120 clockwise – Analyzer need to rotate anticlock wise 120

5. If one enantiomer rotate light 120 clockwise

Another enantiomer rotate light anticlock wise 120

How polarimeter detect optical isomer ?

6. Racemic Mix = enantiomers in equal amt (equimolar) , cancel each other rotation

1st polarizer

1st polarizer

sample optically active

sample optically inactive = Optical activity ability- to rotate plane of polarised light Optically active isomers – presence of asymmetrical/chiral centre - carbon bond to 4 diff gp

Product from natural sources/catalysed by enzyme • give 1 pure optically active enantiomer • chiral and found in single enantiomer – optically active

Products synthesised chemically • give 2 enantiomer in equal amt /racemic mix • optically inactive rotation cancel out each other

Light source

1st polarizer

Tube containing sample which able to rotate polarized light

2nd polarizer (Analyzer)

Polarizer tube

Rotated clockwise

How Polarimeter works ?

R – inactive

Racemate mix ibuprofen S – active

Racemate mix ibuprofen Ibuprofen (painkiller)

Click here notes isomers

R limonene S limonene

CH3

CH3

CH3

Product from natural source/catalysed by enzyme • give 1 pure optically active enantiomer • chiral and found in single enantiomer – optically active

Product synthesised chemically • give 2 enantiomer in equal amt /racemic mix • optically inactive rotation cancel out each other

R – inactive Racemate mix ibuprofen

S – active Racemate mix ibuprofen

Ibuprofen (painkiller) R limonene S limonene

CH3

CH3

CH3

Stereoisomerism

Mirror image / enantiomers Same chemical/physical property except rotation of polarized light

Source/smell orange

Source/smell lemon

Mirror image / enantiomers Same chemical/physical property except rotation of polarized light

R carvone S carvone

Mirror image / enantiomers Same chemical/physical property except rotation of polarized light

Source/smell spearmint

Source/smell caraway seed

R Thalidomide (sedative) S Thalidomide (teratogenic)

• Drug company make drug with R and S (racemic mix) • Thalidomide exist as optical isomers • Enantiomers (R) and (S) • (R) effective against morning sickness • S teratogenic, birth and limb defect

Our body synthesise enzyme which have active site for only one enantiomer

Mirror image / enantiomers

Thalidomide (pregnancy)

• (S) cause limb defect / shortening of arm /leg • (R) is effective drug • Body convert (R) to (S) by racemisation process, produce racemic mix (R)/(S)

• Most drug in racemic mix equal (R) and (S)

• Cheaper to synthesise racemic mix than pure enantiomer

• Single enantiomer appear to be more effective than racemic mix

• Clinical trial is essential to ensure no harmful side effect

(S), effective as pain relief (R) has no side effect!

March 2010 - Published in Science by Takumi Ito. Click HERE for info

Defect Limb due to Thalidomide • (S) bind /inactivate protein cereblon, which involve in limb formation. • Inactivation, lead to a teratogenic effect on LIMB DEFORMITIES

Published in Science ..... • Hiroshi Handa /Takumi Ito - Developed tiny beads with Thalidomide attach. • Thalidomide beads mix with cells extract • Protein Cereblon was bounded on beads • Lack Protein Cereblon during embryo development, cause limb deformities

Click HERE for info/source

http://www.rsc.org/chemistryworld/news/2010/march/11031001.asp

http://news.bbc.co.uk/2/hi/science/nature/8562998.stm

http://news.sciencemag.org/sciencenow/2010/03/-thalidomide-ranks-as-one.html

Scientist discovered how Thalidomide caused Malformed Limb

History of Thalidomide 1954 - Thalidomide for morning sickness. 1961 - Withdrawn, teratogenicity, birth defects result .

1990 - FDA approved for leprosy (skin disease) 1998 - FDA approved for multiple myeloma, (cancer of plasma cells in blood)

2004 - Lenalidomide derived from Thalido able to strengthen immune cells and effective against blood cancers 2011 - Thalidomide + Lenalidomide inhibit formation of new blood vessels ( anti-angiogenic) of tumor cells, Tumors unable to grow due to lack of nutrition. Researchers testing thalidomide in trials for other HIV and Crohn’s disease.

Write structural formula isomers for C4H9OH, state which isomer show optical isomerism

Butan -1-ol Butan-2-ol 2-methylpropan-2-ol 2-methylpropan-1-ol

All structural isomers

Stereoisomers (Optical Isomers)

Write structural formula of cyclic isomers for C3H4CI2, state type of isomerism

Structural formula

Geometric Isomers Cis/Tans isomerism

Optical Isomers Enantiomer, mirror image

Cyclic ring geometric isomers

CH3-CH2-CH2-CH3 ׀

OH

CH3-CH2-CH-CH3 ׀

OH

CH3 ׀

CH3-C-OH

׀

CH3

CH3-CH-CH2-OH ׀

CH3

chiral centre

chiral centre

CI CI

CI

CI

H

H H H

H

H H H CI

CI CI CI

Trans 1, 2 dichlorocyclopropane Cis 1, 2 dichlorocyclopropane Stereoisomers (Optical Isomers)

CI CI CI CI

H H H H

chiral centre chiral centre

* *

Optical Isomerism

Which carbon has chiral center?

Draw all stereoisomers CHBr=CHCH(OH)CH3

CHBr=CHCH(OH)CH3

Optical isomers Geometric isomers

Chiral carbon with 4 diff gp Double bond prevent bond rotation

Cis / Z Trans / E

CH3CH2C*H(CH3)(CI) CH3C*H(NH2)COOH CH3C*H(OH)CH2OH C2H5C*H(OH)CH2OH

C2H5

H H ׀ ׀

C = C

׀ ׀ Br CH(OH)CH3

H CH(OH)CH3 ׀ ׀

C = C

׀ ׀ Br H

H ׀

CHBr=CH-C–CH3

׀ OH

H ׀

CH3-C-CH=CHBr

׀ OH

R (enantiomer) S (enantiomer)

chiral centre

Non chiral centre

NOT mirror image superimposable

χ rotate it

They are same. Superimposable Mirror image

Non superimposable

chiral centre

Optical Isomers

Enantiomers Diastereomers

Same connectivity Have chiral carbon

Non superimposable Mirror image each other

Same connectivity Have chiral carbon

Non superimposable No Mirror image

diff chemical/physical property

2 chiral centre 22 = 4 stereoisomer 3 chiral centre 23 = 8 stereoisomer

click here to view diastereomers

same chemical/physical property

Mirror image Not Mirror image

diff configuration at one or more of equivalent stereocentre

chiral centre

not mirror image same configuration

mirror image diff configuration

2, 3 - dibromopentane

Diastereomers

A B C D

Enantiomer/mirror image Enantiomer/mirror image

Diastereomer/NOT mirror image

Enantiomer/mirror image Diastereomer/NOT mirror image

2n n = chiral centre

Isomers with same Molecular Formula and Structural Formula but diff spatial arrangement

• At least 1 asymmetric / chiral carbon / stereocentre , bonded to 4 diff gp

• NH2CH(R)COOH show optical isomerism

• Optical isomers/mirror images call enantiomers (cannot superimpose on each other)

Optical Isomers

chiral carbon – 4 diff gp

Non superimposable

Non superimposable

click here diastereomers

Optical Isomers

Enantiomers Diastereomers

Same connectivity Have chiral carbon

Non superimposable Mirror image each other

Same connectivity Have chiral carbon

Non superimposable No Mirror image

diff chemical/physical property

click here diastereomers

same chemical/physical property

Mirror image Not Mirror image

diff configuration at one or more of equivalent stereocentre

chiral centre

not mirror image same configuration

mirror image diff configuration

Video on diastereomers