Chapter 12: Alcohols and

Phenols

Based on McMurry’s Organic Chemistry, 7th edition

2كيمياء عضوية صيدلانية

3المحاضرة

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Alcohols and Phenols

Alcohols contain an OH group connected to a a saturated C (sp3)

They are important solvents and synthesis intermediates

Phenols contain an OH group connected to a carbon in a benzene ring

Methanol, CH3OH, called methyl alcohol, is a common solvent, a fuel additive, produced in large quantities

Ethanol, CH3CH2OH, called ethyl alcohol, is a solvent, fuel, beverage

Phenol, C6H5OH (“phenyl alcohol”) has various uses - it gives its name to the general class of compounds

OH groups bonded to vinylic, sp2-hybridized carbons are called enols

These groups lie at the heart of biological chemistry

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17.1 Naming Alcohols and Phenols

General classifications of alcohols based on

substitution on C to which OH is attached

Methyl (C has 3 H’s), Primary (1°) (C has two

H’s, one R), secondary (2°) (C has one H,

two R’s), tertiary (3°) (C has no H, 3 R’s),

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IUPAC Rules for Naming Alcohols

Select the longest carbon chain containing the hydroxyl

group, and derive the parent name by replacing the -eending of the corresponding alkane with -ol

Number the chain from the end nearer the hydroxyl group

Number substituents according to position on chain, listing

the substituents in alphabetical order

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Naming Phenols

Use “phenol” (the French name for benzene)

as the parent hydrocarbon name, rather than

benzene

Name substituents on aromatic ring by their

position from OH

Give IUPAC names for the following compounds

a )5-methylhexane-2,4-diol.,b)2-methyl-4-phenylbutan-2-ol.,c)4,4-dimethylcyclohexanol

d) trans-2-bromocyclopentanol., e)4-bromo-3-methylphenol., f) cyclopent-2-en-1-ol

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Draw structures corresponding to the

following IUPAC names:

a) (z)-2-Ethylbut-2-en-1-ol

b) Cyclohex-3-en-1ol

c) Trans-3-chlorocycloheptanol

d) Pentane-1,4-dio

e) 2,6-dimethylphenol

f) O-(2-hydroxyethyl)phenol

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17.2 Properties of Alcohols and

Phenols The structure around O of the alcohol or phenol is similar to that in

water, sp3 hybridized

Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides

A positively polarized OH hydrogen atom from one molecule is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another molecule

This produces a force that holds the two molecules together

These intermolecular attractions are present in solution but not in the gas phase, thus raising the boiling point of the solution

The decrease in boiling point with increasing

substitution of the OH-bearing carbon.

Butan-1-ol,bp 117.5 C

Butan-2-ol,bp 99.5 C

2-Methylpropan-2-ol, bp 82.2 C

Hydrogen-bonding is more difficult in hindered

alcohols.

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Properties of Alcohols and

Phenols: Acidity and Basicity

Alcohols and phenols are weakly basic and weakly acidic

Reversibly Protonated by strong acids to yield oxonium ions, ROH2

+

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Alcohols and Phenols are Weak

Brønsted Acids

Can transfer a proton to water to a very small

extent

Produces H3O+ and an alkoxide ion, RO, or

a phenoxide ion, ArO

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Acidity Measurements

The acidity constant, Ka, measures the extent to which a Brønsted acid transfers a proton to water

[A] [H3O+]

Ka = ————— and pKa = log Ka

[HA]

Relative acidities are more conveniently presented on a logarithmic scale, pKa, which is directly proportional to the free energy of the equilibrium

Differences in pKa correspond to differences in free energy

Table 17.1 presents a range of acids and their pKa

values

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pKa Values for Typical OH Compounds

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Relative Acidities of Alcohols

Simple alcohols are about as acidic as water

Alkyl groups make an alcohol a weaker acid

The more easily the alkoxide ion is solvated by water

Steric effects are important

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Inductive Effects

Electron-withdrawing groups make an alcohol a

stronger acid by stabilizing the conjugate base

(alkoxide) nonafluro-tert-butyl alcohol pka 5.4, tert-

butyl alcohol pka18

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Generating Alkoxides from Alcohols Alcohols are weak acids – requires a strong base to

form an alkoxide such as sodium hydrideNaH, sodium amide NaNH2, and Grignard reagents (RMgX)

Alkoxides are bases used as reagents in organic chemistry

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Phenol Acidity

Phenols (pKa ~10) are much more acidic than alcohols (pKa ~ 16) due to resonance stabilization of the phenoxide ion

Phenols react with NaOH solutions (but alcohols do not), forming salts that are soluble in dilute aqueous solution

A phenolic component can be separated from an organic solution by extraction into basic aqueous solution and is isolated after acid is added to the solution

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17.3 Preparation of Alcohols: A

Review

Alcohols are derived from many types of compounds

The alcohol hydroxyl can be converted to many other functional groups

This makes alcohols useful in synthesis

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Review: Preparation of Alcohols by

Hydration of Alkenes

Hydroboration/oxidation: syn, non-Markovnikov hydration

Oxymercuration/reduction: Markovnikov hydration

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1,2-Diols

Prepared Cis-1,2-diols from hydroxylation of an

alkene with OsO4 followed by reduction with NaHSO3

Trans-1,2-diols from acid-catalyzed hydrolysis of

epoxides

Predict the products of the following reaction:

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17.4 Alcohols from Reduction of

Carbonyl Compounds

Reduction of a carbonyl compound in general gives an alcohol

Note that organic reduction reactions add the equivalent of H2 to a molecule

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Reduction of Aldehydes and Ketones

Aldehydes gives primary alcohols

Ketones gives secondary alcohols

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Reduction Reagent: Sodium

Borohydride NaBH4 is not sensitive to moisture and it does not reduce other

common functional groups

Lithium aluminum hydride (LiAlH4) is more powerful, less specific, and very reactive with water(explosive when heat above 120 c )

Both add the equivalent of “H-”

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Mechanism of Reduction

The reagent adds the equivalent of hydride ion to the carbon of C=O and polarizes the carbonyl group (an alkoxide ion) protonated by by addition of H3O+

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Reduction of Carboxylic Acids and

Esters

Carboxylic acids and esters are reduced to give

primary alcohols

LiAlH4 is used because NaBH4 is not effective

What reagent would you use to accomplish

each of following reactions?

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What carbonyl compounds give the following alcohols

on reduction with LiAlH4?Show all possibilities.

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17.5 Alcohols from Reaction of Carbonyl

Compounds with Grignard Reagents

Alkyl, aryl, and vinylic halides react with magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX

Grignard reagents react with carbonyl compounds to yield alcohols

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Reactions of Grignard Reagents with

Carbonyl Compounds

Using a Grignard Reaction to

Synthesize an Alcohol How could you use the addition of a Grignard reagent

to a ketone to synthesize 2-phenylbutane-2-ol?

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Reactions of Esters and Grignard

Reagents

Ester react with Grignard reagent to yields tertiary alcohols.

Grignard reagents do not add to carboxylic acids –they undergo an acid-base reaction, generating the hydrocarbon and the magnesium salt of the acid.

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Grignard Reagents and Other Functional

Groups in the Same Molecule

Can't be prepared if there are reactive functional

groups in the same molecule, including proton donors

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Mechanism of the Addition of a

Grignard Reagent

Grignard reagents act as nucleophilic carbon anions

(carbanions, : R) in adding to a carbonyl group

The intermediate alkoxide is then protonated to

produce the alcohol

Show the products obtained from addition of

methylmagnesium bromide to the folowing compounds:

a) Cyclopentanone ,b) Benzophenone (diphenyl ketone)

,c) Hexan-3-one

Use Grignard reaction to prepare the following alcohols:

a) 2-methylpropan-2-ol b) 1-methylcyclohexanol

c) 3-methylpentan-3-ol d ) 2-phenylbutan-2-ol

e) benzyl alcohol f) 4-methylpentan-1-ol

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17.6 Reactions of Alcohols

Conversion of alcohols into alkyl halides:

- 3˚ alcohols react with HCl or HBr by SN1 through carbocation intermediate

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-1˚ and 2˚ alcohols converted into halides by treatment with SOCl2 or PBr3 via SN2 mechanism

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Conversion of Alcohols into Tosylates

Reaction with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine yields alkyl tosylates, ROTos

Formation of the tosylate does not involve the C–O bond so configuration at a chirality center .

Alkyl tosylates react like alkyl halides, undergoing both SN1 and SN2 substitution reactions

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Dehydration of Alcohols to Yield

Alkenes

The general reaction: forming an alkene from an alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give bond

Specific reagents are needed

How would you carry out the follwing

transformation, a step used in the commercial

synthesis of (s)- ibuprofen?

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Acid- Catalyzed Dehydration

Tertiary alcohols are readily dehydrated with acid

Secondary alcohols require severe conditions (75% H2SO4, 100°C) - sensitive molecules don't survive

Primary alcohols require very harsh conditions –impractical

Reactivity is the result of the nature of the carbocation intermediate

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Dehydration with POCl3

Phosphorus oxychloride (POCl3)in the amine solvent

pyridine can lead to dehydration of secondary and

tertiary alcohols at low temperatures

What major product would you expect from

dehydration of the following alcohols with

POCl3 in in pyridine?

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Conversion of Alcohols into

Esters

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17.7 Oxidation of Alcohols

Can be accomplished by inorganic reagents, such as KMnO4, CrO3, and Na2Cr2O7 or by more selective,

expensive reagents

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Oxidation of Primary Alcohols

To aldehyde: pyridinium chlorochromate (PCC,

C5H6NCrO3Cl) in dichloromethane

Other reagents produce carboxylic acids

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Oxidation of Secondary Alcohols

Effective with inexpensive reagents such as Na2Cr2O7 in acetic acid

PCC is used for sensitive alcohols at lower temperatures

What alcohols would give the following products on

oxidation?

What products would you expect from oxidation of

the following compounds with CrO3 in aqueous acid?

With pyridinium chlorochromate(PCC)?

a) Hexan-1-ol b) Hexan-2-ol c) Hexanal

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17.8 Protection of Alcohols

Hydroxyl groups can easily transfer their proton to a

basic reagent

This can prevent desired reactions

Converting the hydroxyl to a (removable) functional

group without an acidic proton protects the alcohol

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Methods to Protect Alcohols

Reaction with chlorotrimethylsilane in the presence of base yields an unreactive trimethylsilyl (TMS) ether

The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol

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Protection-Deprotection

An example of TMS-alcohol protection in a synthesis

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17.9 Phenols and Their Uses

Industrial process from readily available cumene

Cumene reacts with air to forms cumene

hydroperoxide with oxygen at high temperature

Converted into phenol and acetone by acid

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BHT: butylated hydroxytoluene (food preservatives)

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17.10 Reactions of Phenols

The hydroxyl group is a strongly activating, making phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions

Reaction of a phenol with strong oxidizing agents as potassium nitrosodisulfonate (Fremys salt) yields a quinone

Quinones can be easily reduced to

hydroquinones(p-dihydroxybenzenes) by

reagents such NaBH4 and SnCl2.

Hydroquinones can be easily back to

quinones by Fremy's salt

Fremy's salt [(KSO3)2NO] works under mild

conditions through a radical mechanism

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