Biological ChemistryFIRST YEAR ORGANIC CHEMISTRY

Lecture Six

Alcohols and Ethers

Convenor : Dr. Fawaz Aldabbagh

Alcohols and Ethers

Alcohols and Ethers can be regarded as derivatives of water in which one or two of the H atoms has been replaced by an alkyl group

Electronegativity of oxygen causes an unsymmetrical distribution of charge

Saturated molecules are sp3

hybridized

OH H

104.5o

0.96 AoWater, H2OO

C H

108.5o

0.96 Ao

Methanol, CH3OH

HH

H

1.43 Ao

OC C

111.7o

Methoxymethane, CH3OCH3

HH

H

1.43 Ao

H

HH

109.5o1.10 Ao

OH3C H

- I (net dipole)

Alcohols are found to have much higher bpt than those of alkanes or haloalkanes of comparable size, e.g. Methanol (65 oC), Chloromethane and Methane are gases ; Ethanol (78.5 oC), Chloroethane (12 oC) and Ethane is a gas

Methanol and Ethanol are classed as Polar Molecules (Hydrophilic) – They are Infinitely Soluble in Water

Why? Answer – Hydrogen Bonding

H-bonds weaker than covalent bonds, although these bonds can be continually broken and reformed – a highly ordered structure results – H-Bonding to water can also occur

Water (mw = 18) is a liquid, bpt 100oC – otherwise a gas

R

OH

HO

R

R

OH

H

OH

HO

H

H

OH

As R-group increases in size, so does the solubility in non-polar solvents

As the number –OHs increases so does solubility in waterBpt increase with chain length and number of –OHs

Methanol, CH3OH

- Solvent in varnishes, paint- Racing Car Fuel (easy to put out flames)- Highly Toxic – “Blindness” - Formaldehyde

Ethanol, CH3OH

-Drinking Alcohol

- 50% Ethanol is flammable

C O

H

H

H

C

H

H

H C O

H

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

Hydrophobic end

Hydrophilic end1-PentanolEthanol

H3C OH

Alcohol Dehydrogenase

O

CH H

O

CH OH

[O]In the Liver

Alcohol Dehydrogenase

O

CH3C H

O

CH3C OH

[O]In the Liver

CH3CH2OH

AcetaldehydeAcetic Acid

Odour on your breath

Symptoms - Hang-over

Preparation of Ethanol

- Fermentation of Sugar – Break down of sugar to CO2 and Ethanol by Yeast Enzymes

- Industrial Process – Hydration of Ethene

CH3CH2OH

H

H

H

H

H3PO4 , 300C

H2O

Ethanol content; Beer, 3-9% ; Wine, 11-13% ; Whisky, 40-45% ; Vanilla Extracts, 35% ; Night Nurse, 25% ; Listerine, 25%

CH3 OH

hydroxy or alcohol group

CH2 OHCH3 CH2 OHCH2CH3

CH3 CH OH

CH3

CH2 CH CH2

CH2 OH

CH3CH3

Naming Alcohols

Methyl alcohol(methanol) Ethyl alcohol

(ethanol)Propyl alcohol (propanol)

Isopropyl alcohol 2-Ethyl-1-butanol

Naming Alcohols

Polyhydroxy alcohols are alcohols that possess more than one hydroxyl group

CH2 CH2

HO OH

1,2-Ethanediol (ethylene glycol)1,2-Propanediol (propylene glycol)

1,2,3-Propanetriol (glycerol)

CH CH2

OH

CH3

HO

CH CH2

OH

CH2

HOHO

Extremely ToxicCalcium Oxalate crystallises in the kidney leading to renal problems

Harmless

C OHC

OO

HOLiver Enzymes Oxalic acid

CH2 CH2

OHHO

CH CH2

OH

CH3 C OHC

OO

H3CLiver Enzymes Pyruvic acidHO

Alcohols are weak Acids

The Conjugate base of an alcohol is an alkoxide ionBecause most alcohols are weaker acids than water ; they’re respective alkoxide is a

stronger base than hydroxide ion OH -

pKa CH3OH (15.5), H2O (15.74), CH3CH2OH (15.9), (CH3)3COH (18.0)

H

C OHH3C

H

CH3

C OHH3C

H

CH3

C OHH3C

CH3

Primary (1o) AlcoholSecondary (2o) Alcohol

Tertiary (3o) Alcohol

R O H

H

O H R O +

H

O HH

AlcoholAlkoxide

Relative Acidity ; H2O > ROH > C CR H > RH

Weak acids make Poor Leaving Groups in Organic ReactionsStrong Acids have Conjugate Bases that are Good Leaving Groups in Organic Reactions

Sodium Ethoxide

-OH is a Poor Leaving Group

We have to convert OH into a Good Leaving Group

CH3CH2OH + Na CH3CH2 O Na + H2

Vigorous Reaction

2 2 2

C O H H A+ C O H

H+ A

Strong Acid

Protonated Alcohol

C O H

H

Nu

C Nu H2O+

OMs and OTs are excellent leaving groups in NucleophilicSubstitution Reactions- Derivatives of Sulfuric Acid

C O HBase

C O Na

C O

O

S CH3

O

Cl C O SO2CH3

Cl MsC OMs

Methanesulfonyl chloride

Alkanesulfonate(Alkane Mesylate)

Similiarly,

S

O

O

Cl

CH3CH2O H

+

CH3CH2O S

O

O

CH3

NaOH , - HCl

CH3

p-Toluenesulfonyl chloride(Tosyl Chloride)

CH3CH2-OTs

Ethyl-p-toluenesulfonate(Ethyltosylate)

O

S OH

O

HO

Sulfuric Acid

Other Good Leaving Groups ;R-I > R-Br > R-Cl > R-F -------------It follows Acid StrengthHI > HBr > HCl > HF

SN2 – Substitution, Nucleophilic, Bimolecular

Rate = k [CH3CH2OTs] [ Nu- ] ---------Bimolecular

Backside Nucleophilic Attack – Inversion in Configuration

Concerted Mechanism

Optically ActiveEnantiomericaly Pure

C Br

H3C

HC6H13HO

CHO

CH3

H C6H13

BrCH3

HO

C6H13

H

Transition StateR-(-)-2-BromooctaneS-(+)-2-Octanol

Inversion of Stereochemistry

C OTs

H3C

HH

Nu

CNu

CH3

H HOTs

CH3Nu

HH

Transition State

SN1 – Substitution, Nucleophilic, Unimolecular

(CH3)3CCl + 2 H2O (CH3)3COH + 2 H3O+ + Cl -

                               

Professor George OlahNobel Prize 1994

Carbocation is sp2-planar

CH3

CH3C

CH3

Cl

CH2

CH3H3C+ Cl

Slow Step (RDS)

Aided by polar Solvent Stable 3o Carbocation

ions are stabilized via solvation

CH2

CH3H3C

Fast Step

HO

HFront or Backside Attack

CH3

CH3C

CH3

O

tert-Butyl alcohol

H

H

CH3

CH3C

CH3

O H

- H+

CRR

RCR

R

HCR

H

H> >

R groups are electron releasing - delocalise the positive charge

more stable

H3CH2CH2C

C Br

H3CH2CH3C CH2CH2CH3

CHO

CH2CH3CH3

H3CH2CH2C

C OH

H3CH2CH3C

+

- HBr

S-3-Bromo-3-methylhexane

1:1 Mixture of R- and S-3-Methyl-3-hexanol

Evidence for SN1 is Racemization of an optically active compound

The Carbocation intermediate is attacked by water from either side by the same rate Phenols

OH OHOH

OHH3C

Phenol

4-Methylphenol

1-Naphthol 2-Naphthol

Much high bpt, because of H-Bonding (e.g. Phenol, 182C, toluene, 111C

Phenols are much stronger acids than alcohols

O

CH3

H3CCH3

cyclohexene

phenol

cyclic ether

Tetrahydrocannabinol

OH

OH OH

pKa = 18 pKa = 10

OHO O O

Resonance Stabilised Phenoxide anion

ETHERS, RO-OR CH3CH2 O CH2CH3

CH3CH2 O

H3C O

Ethoxy group

Methoxy group

Diethyl Ether

1-Propoxypropane

Methoxybenzene

Methoxycyclohexane

Bpt are similar to alkanes – No H-bonding to one anotherBut are soluble in water- H-bonding to water - PolarFlammable – Ether can cause flash firesLow Reactivity – Make Good Reaction Solvents

OTetrahydrofuran (THF) O

OFuran Pyran

Cyclic Ethers

Non-Flammable Anaesthetics

Cl

CH

F

C

F

F

O C H

F

FEnflurane

F

CF

F

C

H

Cl

O C H

F

FIsoflurane

H3CO O

OCH3