Chapter 17:

Alcohols and Phenols

Based on McMurry’s Organic Chemistry, 7th edition

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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 diverse uses - it gives its name to the general class of compounds

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

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Why this Chapter?

To begin to study oxygen-containing

functional groups

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 -e

ending 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, not benzene

Name substituents on aromatic ring by their

position from OH

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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 elevating the boiling point of the solution

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Properties of Alcohols and

Phenols: Acidity and Basicity

Weakly basic and weakly acidic

Alcohols are weak Brønsted bases

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 the more its formation is energetically favored

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)

(alcohol) (alcohol)

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Generating Alkoxides from

Alcohols

Alcohols are

weak acids –

requires a strong

base to form an

alkoxide such as

NaH, 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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Nitro-Phenols

Phenols with nitro groups at the ortho and para

positions are much stronger acids

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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

Regiospecific Hydration of Alkenes

Hydroboration/oxidation: syn, non-Markovnikov hydration

Oxymercuration/reduction: Markovnikov hydration

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MARKOVNIKOV’S RULE

Named for Vladimir W. Markovnikov (1838–1904),

this rule originally stated that the addition of HX (Xhalogen) to an

unsymmetrically substituted alkene occurs with attachment of the hydrogen

to the carbon atom of the double bond having more hydrogens.

Markovnikov addition: (a) Markovnikov product via a tertiary carbocation and

(b) anti-Markovnikov product (minor product) via a much less stable primary

carbocation.

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Addition of non-symmetrical reagent to a non-symmetrical

alkene, then two isomeric products that are constitutional

isomers can be obtained.

For example,

the reaction of HCl with propene gives 1-chloropropane and

2-chloropropane.

Normally, 2-chloropropane is the major product.

Since one product is favoured over the other, the reaction is

said to be regioselective.

If 2-chloropropane were the only product then the reaction is

said to be regiospecific

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Preparation of Alcohols by

Regiospecific Hydration of Alkenes

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1,2-Diols

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

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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

Both add the equivalent of “H-” (+1H)

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Mechanism of Reduction

The reagent adds the equivalent of hydride to the carbon of C=O and polarizes the group as well

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Reduction of Carboxylic Acids

and Esters

Carboxylic acids and esters are reduced to give

primary alcohols (+2H)

LiAlH4 is used because NaBH4 is not effective

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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

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Reactions of Esters and

Grignard Reagents

Yields tertiary alcohols in which two of the substituents carbon come from the Grignard reagent

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

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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

17.7 Some Reactions of Alcohols

Two general classes of reaction

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

carbocation intermediate

- 1˚ and 2˚ alcohols converted into halides by treatment with

SOCl2 or PBr3 via SN2 mechanism

Conversion of alcohols into

alkyl halides:

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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 is maintained

Alkyl tosylates react like alkyl halides

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Stereochemical Uses of Tosylates

The SN2 reaction of an alcohol via a tosylate,

produces inversion at the chirality center

The SN2 reaction of an alcohol via an alkyl halide

proceeds with two inversions, giving product with

same arrangement as starting alcohol

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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

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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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Figure 17.6

Mechanism of the acid-

catalyzed dehydration of

an alcohol to yield an

alkene.

The process is an E1

reaction and involves a

carbocation intermediate.

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Dehydration with POCl3

Phosphorus oxychloride in the amine solvent pyridine

can lead to dehydration of secondary and tertiary

alcohols at low temperatures

An E2 via an intermediate ester of POCl2 (see Figure

17.7)

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Fjgure 17.7

Mechanism of the dehydration

of secondary and tertiary

alcohols by reaction with

POCI3 in pyridine.

The reaction is an E2 process.

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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

Pyridinium ChloroChromate

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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

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Mechanism of Chromic Acid

Oxidation

Alcohol forms a chromate ester followed by

elimination with electron transfer to give ketone

The mechanism was determined by observing the

effects of isotopes on rates

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How Alcohol Is Metabolized in

the Human Body

Alcohol dehydrogenase converts methanol into

formaldehyde (H2CO)

and aldehyde dehydrogenase turns this formaldehyde into a

formic acid radical.

Both formaldehyde and formic acid are highly poisonous and

quickly dead to blindness and death.

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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

Forms cumene hydroperoxide with oxygen at high

temperature

Converted into phenol and acetone by acid

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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 yields a quinone

Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism

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Quinones in Nature

Ubiquinones mediate electron-transfer processes

involved in energy production through their redox

reactions

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17.11 Spectroscopy of Alcohols

and Phenols Characteristic O–H stretching absorption at 3300 to

3600 cm1 in the infrared

Sharp absorption near 3600 cm-1 except if H-bonded:

then broad absorption 3300 to 3400 cm1 range

Strong C–O stretching absorption near 1050 cm1

(See Figure 17.11)

Phenol OH absorbs near 3500 cm-1

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Nuclear Magnetic Resonance

Spectroscopy

13C NMR: C bonded to OH absorbs at a lower field, 50 to 80

1H NMR: electron-withdrawing effect of the nearby oxygen, absorbs at 3.5 to 4 (See Figure 17-13)

Usually no spin-spin coupling between O–H proton and neighboring protons on C due to exchange reactions with moisture or acids

Spin–spin splitting is observed between protons on the oxygen-bearing carbon and other neighbors

Phenol O–H protons absorb at 3 to 8

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Mass Spectrometry

Alcohols undergo alpha cleavage, a C–C bond nearest the hydroxyl group is broken, yielding a neutral radical plus a charged oxygen-containing fragment

Alcohols undergo dehydration to yield an alkene radical anion