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

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!

Asymmetric/ chiral carbon/ stereocentre , bonded to 4 diff gp

Amino acid Amino acid – pair enantiomers

Stereochemistry in protein

Biologically-active molecule are chiral, Most are L- amino acid – tasteless Synthesize D amino acid – sweet Due to taste receptor in our body

Chiral carbon

D amino acid Enantiomer(R)

Rotate clockwise

L amino acid Enantiomer(S)

Rotate anticlock wise L D

Cis Isomer Atom on same side

Trans Isomer Atom on diff side

Stereochemistry in lipids

Geometric Isomers

Long hydrocarbon fatty acid chain

Saturated (No C = C)

Unsaturated ( C = C)

Fatty acid Saturated, unsaturated and polyunsaturated

Presence cis /trans isomers Naturally fatty acids – cis form

Cis Isomer Atom on same side

Trans Isomer Atom on diff side

Stereochemistry in lipids

Geometric Isomers

Long hydrocarbon fatty acid chain

Saturated (No C = C)

Unsaturated ( C = C)

Fatty acid Saturated, unsaturated and polyunsaturated

Presence cis /trans isomers Naturally fatty acids – cis form

Cis fatty acid Kink/ bend – unable to pack closely

Weaker intermolecular forces attraction VDF lower – m/p lower - liquid

Trans fatty acid Straight chain – close packed together Strong intermolecular forces attraction

VDF higher – m/p high - Solid

Solidify in arteries – risk heart attack (artherosclerosis)

Good fatty acid

Mono unsaturated (1 C =C )

Cis transform to trans form Trans able to pack close together High m/p – solid form more stable to temp/oxi High risk – heart attack Increase level LDL (bad cholesterol)

Polyunsaturated (> 2C = C)

Trans fats (straight)

Convert H2 Ni catalyst

Cis (bend)

complete hydrogenation

partial hydrogenation

Lipids chemistry

Rancidity of lipids

Condensation – Form triglyceride

+

Hydrolysis – Glycerol and Fatty acids

Hydrolytic rancidity Oxidative rancidity

Presence H2O/heat Hydrolysis rxn – (water)- ester link broken

Presence O2/light/enzymes Oxidative rxn- react with C=C (unsaturation)

Free radical mechanism

LDL vs HDL

LDL High ratio lipid to protein More lipid/Less protein

Carry lipid/cholesterol to artery Bad cholesterol

lipid

protein

HDL High ratio protein to lipid More protein/Less lipid

Carry cholesterol from artery to liver Good cholesterol

VS lipid

protein

Stereochemistry in lipids

Presence cis /trans isomers Naturally fatty acids – cis form

Cis fatty acid Kink/ bend – unable to pack closely

Weaker intermolecular forces attraction VDF lower – m/p lower - liquid

Good fatty acid Mono unsaturated (1 C =C ) Polyunsaturated (> 2C = C)

Omega 3 fatty acid Omega 6 fatty acid

Omega-3 fatty acid reduce blood triglyceride Increase HDL level - HDL as "good cholesterol" they transport cholesterol

out of blood artery walls, and transport back to liver Cholesterol carry in HDL away from blood

ALA alpha linolenic acid (3 cis C=C)

EPA eicosapentaenoic acid (5 cis C=C)

DHA Docosahexaenoic acid (6 cis C=C)

3

source omega 3 fatty acid

Linoleic acid (2 cis C=C)

Arachidonic acid (4 cis C=C)

Double bond start at C3 Double bond start at C6

Fatty acid Molar mass

C =C bond

Melting point

Linoleic acid 278 3 -11

Linoleic acid 280 2 -5

Oleic acid 282 1 16

Stearic acid 284 0 70

Number C = C increase ↑ (unsaturation ↑) ↓

Lower ability to pack – Due to kink/bend structure ↓

Lower IMF/VDF ↓ between molecule ↓

Melting point decrease ↓ (liquid form)

Iodine number- Measure degree saturation Iodine number = number gram of I2 react with 100g fat

1 mol Fat – 1 mol I2 (254g I2)

C = C – C = C + 2I2 → C – C – C – C

1 mol Fat – 2 mol I2 (508g I2)

1 C =C in fat

2 C =C in fat

Stereochemistry in lipids

Fatty acid Molar mass

C =C bond

Melting point

Linoleic acid 278 3 -11

Linoleic acid 280 2 -5

Oleic acid 282 1 16

Stearic acid 284 0 70

Number C = C increase ↑ (unsaturation ↑) ↓

Lower ability to pack – Due to kink/bend structure ↓

Lower IMF/VDF ↓ between molecule ↓

Melting point decrease ↓ (liquid form)

Iodine number- Measure degree saturation Iodine number = number gram of I2 react with 100g fat

Linoleic acid C18H32O2. Determine iodine number of linoleic acid

1 mol Fat – 1 mol I2 (254g I2)

C = C – C = C + 2I2 → C – C – C – C

1 mol Fat – 2 mol I2 (508g I2)

1 C =C in fat

2 C =C in fat

Linoleic acid (2 cis C=C)

C = C – C = C + 2I2 → C – C – C – C

1 mol linoleic acid – 2 mol I2 (508g I2) (RMM 280) 280 g linoleic acid – 508 g I2

2 C =C in fat

Iodine number = number gram I2 react with 100g fat

508 g I2 – 280 g linoleic acid 100 g I2 – (280 x 100)/508 g I2

Iodine number = 181

Sample fat contain 0.02 mol fatty acid react with 10.16 g I2

Determine number C =C bonds

0.02 mol acid – 0.04 mol I2 1 mol acid – 2 mol I2 2 C =C in acid

RMM I2 = 253.8 Moles I2 = 10.16/253.8 = 0.04 mol I2

Nutrient Energy/kJg-1

Carbohydrates 17

Protein 17

Lipid 38

Fat - more C- H bond -more reduced Carbohydrates – more C-O bond–already oxidized More energy when oxidized/combusted

Stereochemistry in lipids

Fatty acid Molar mass

C =C bond

Melting point

Linoleic acid 278 3 -11

Linoleic acid 280 2 -5

Oleic acid 282 1 16

Stearic acid 284 0 70

3 C =C in linolenic

Iodine number = number gram I2 react with 100g fat

Iodine number = 274 274 g I2 – 100 g linoleic acid 761.7 g I2 – 274 g linoleic acid (1 mol)

1 mol linolenic acid – 3 mol I2

2 C =C in acid

RMM I2 = 253.8 Moles I2 = 761.7/253.8 = 3 mol I2

Iodine number palmitic acid (Mr = 256) is 0 Iodine number linolenic acid (Mr = 278) is 274.

Determine number double bonds in linolenic acid

Linoleic acid (Mr = 281) CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Cal vol of 1.00M I2 required to react with 1 g linoleic acid.

Vol 1.0M I2 = 0.00712 dm3 or 71.2 cm3

mol linoleic acid 1/281 = 0.00356 mol

Linoleic acid (2 cis C=C)

1 mol acid – 2 mol I2 (508g I2)

1 mol acid – 2 mol I2

0.00356 mol acid – 0.00712 mol I2

Find number C = C in linolenic acid, C18H30O2, given 7.7 g I2, react with 2.8 g of linolenic acid.

1–mol g 126.902

g 7.7

1–mol g 278.48

g 8.2

:

0.01 mol acid – 0.03 mol I2

1 mol acid – 3 mol I2

mol acid mol I2

3 C =C linolenic

Find iodine number of linoleic acid. CH3(CH2)4(CH═CHCH2)2(CH2)6COOH Mr (280)

Iodine number = number gram I2 react with 100g fat

C = C – C = C + 2I2 → C – C – C – C

1 mol acid – 2 mol I2 (508g I2) 280 g – 508 g I2

100 g - (508 x 100)/280 = 181 g I2

Iodine number = 181

Natural occur sugar –D form Glucose – 4 stereocenter C5 – chiral center further from C1 – OH on right - D form

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

same chemical/physical property

Mirror image Not Mirror image

diff configuration at one or more of equivalent stereocenter

chiral centre

not mirror image same configuration

mirror image diff configuration

Enantiomer/mirror image

2n n = chiral centre

D glucose L - glucose

Glucose Isomers

Stereochemistry in carbohydrates

OH at C1 – bottom ring α glucose

* All chiral center diff configuration

↓ Mirror image

α glucose β glucose

OH at C1 – top ring β glucose

equilibrium bet straight chain – ring form

* *

*

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

same chemical/physical property

Mirror image Not Mirror image

diff configuration at one or more of equivalent stereocenter

chiral centre

not mirror image same configuration

mirror image diff configuration

Enantiomer/mirror image

2n n = chiral centre

D fructose L - fructose

Natural occur sugar –D form Fructose – 3 stereocenter C5 – chiral center further from C1 – OH on right - D form

Fructose Isomers

Stereochemistry in carbohydrates

OH at C2 – bottom ring α fructose

* All chiral center diff configuration

↓ Mirror image

α fructose β fructose

OH at C2 – top ring β fructose

equilibrium bet straight chain – ring form

Natural occur sugar –D form Glucose – 4 stereocenter C5 – chiral center – OH on right - D form

Enantiomer/mirror image

D glucose L - glucose

Glucose Isomers

Stereochemistry in carbohydrates

* All chiral center diff configuration

↓ Mirror image

equilibrium bet straight chain – ring form

Starch/glycogen - α glucose link together (1-4 α glycosidic link) Human – have α amylase recognise α glucose - can digest starch

Starch

α glucose α glucose α glucose

(1-4 α glycosidic link)

Cellulose

Cellulose - β glucose link together – (1-4 β glycosidic link) Cow – have β cellulase recognise β glucose – can digest cellulose

Cellulose – fibre to human – strong long chain - H2 bond bet chain

All OH gp below

(1-4 β glycosidic link)

Β glucose β glucose β glucose β glucose

OH gp alternate

* *

*

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

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

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

Enantiomers and Diastereomers

Diastereomer/NOT mirror image Can separate by physical/chemical mean

Enantiomer/mirror image Cant be separated by physical/chemical mean

3 sugar, same structural formula

2n n = chiral centre

All chiral center diff configuration

↓ Mirror image

Which of the following are enantiomers and diastereomers?

one chiral center diff configuration

Diastereomer/NOT mirror image Can separate by physical/chemical mean

two chiral center diff configuration

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

Stereochemistry in vitamins

RODS Conjugated protein Rhodopsin

Retina – 2 types light sensitive RODS (no colour) and CONES (colour)

Light cause photo isomerization 11 cis retinal → all trans retinal (light)

Cis fit into protein opsin Trans dissociate from protein opsin

Nerve impulse trigger

Rhodopsin made up of

11 cis retinal ↓

Bend ↓

Fit into Opsin

all trans retinal ↓

Straight ↓

Dissociate from Opsin

Light – PHOTO ISOMERIZATION – CIS to TRANS

Opsin (protein) 11 cis retinal (conjugated chromophore)

+

visual cycle

Vit A – source of retinal Lack Vit A – night blindness

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