CH 17: Alcohols and Phenols

Renee Y. Becker

CHM 2211

Valencia Community College

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Alcohols and Phenols

• Alcohols contain an OH group connected to a saturated C (sp3)– They are important solvents and synthesis

intermediates• Enols also contain an OH group connected to an

unsaturated C (sp2)• Phenols contain an OH group connected to a carbon in a

benzene ring

OH

an enol 2

Alcohols and Phenols

• 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

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Naming Alcohols

• General classifications of alcohols based on substitution on C to which OH is attached

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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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Many Alcohols Have Common Names

• These are accepted by IUPAC

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Example 1: Give the IUPAC names for these compounds

OH OH

OH

H3C CH3

OH

HO

2

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4

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Example 2: Draw the following structures

• 2-Ethyl-2-buten-1-ol

• 3-Cyclohexen-1-ol

• 1,4-Pentanediol

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Naming Phenols

• Use “phene” (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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Properties of Alcohols and Phenols: Hydrogen Bonding

• 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

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Alcohols Form Hydrogen Bonds

• 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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Alchols 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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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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Stronger acid

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Inductive Effects

• Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide)

Stronger acid

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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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Example 3:

2 2 K

1

2

3

4

5

OH

OH

OH

NaH

CH3MgBr

CH3Li

NaNH2CH3CH2OH

CH3OH

+

+

+

+

+

22 K

1

2

3

4

5

OH

OH

OH

NaH

CH3MgBr

CH3Li

NaNH2CH3CH2OH

CH3OH

+

+

+

+

+

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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 soluble salts that are soluble in dilute aqueous

• 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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Substituted Phenols

• Can be more or less acidic than phenol itself• An electron-withdrawing substituent makes a

phenol more acidic by delocalizing the negative charge

• Phenols with an electron-donating substituent are less acidic because these substituents concentrate the charge

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Example 4:

p-Nitrobenzyl alcohol is more acidic than benzyl alcohol. Explain.

OH

O2N

OH

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Nitro-Phenols

• Phenols with nitro groups at the ortho and para positions are much stronger acids

• The pKa of 2,4,6-trinitrophenol is 0.6, a very strong acid

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Preparation of Alchols: an Overview

• 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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Preparation of 1,2-Diols

• Review: Cis 1,2-diols from hydroxylation of an alkene with OsO4 followed by reduction with NaHSO3

• In Chapter 18: Trans-1,2-diols from acid-catalyzed hydrolysis of epoxides

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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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Catalytic Hydrogenation:

RCH

O

aldehyde

+ H2Pt, Pd or Ni

RCH2OH

primary alcohol

RCR'O

ketone

+ H2Pt, Pd or Ni

RCHR'secondary alcohol

OH

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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-”

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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

Not a complete mechanism!!!

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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

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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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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

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Examples of Reactions of Grignard Reagents with Carbonyl Compounds

• Formaldehyde reacts with Grignard reagents to yield primary alcohols.

• Aldehydes react with Grignard reagents to yield secondary alcohols.

• Ketones yield tertiary alcohols.

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Examples of 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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Synthesis of Diols

Catalytic hydrogenation:

HCCH2CHCH2CH

O O

CH3

3-Methylpentanedial

H2

Ni, 125oCCH2CH2CHCH2CH2

OH OH

CH3

3-Methyl-1,5-pentanediol

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Some Reactions of Alcohols

• Two general classes of reaction– At the carbon of the C–O bond– At the proton of the O–H bond

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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 (See Figure 17-5)

• Note that Zaitsev’s rule is followed!47

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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 17.6)

Follows an E2 mechanism

N

pyridine

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Mechanism 1: Dehydration of Alcohol (2 or 3 )

HCl

OH

P

O

ClCl

Cl

O+

H

H

N

N

Cl–

N+

H

P

O

ClCl

O–

POCl2

OPOCl2

+

+

++

+

H C l

OH

P

O

ClCl

Cl

O+

H

H

N

N

Cl–

N+

H

P

O

ClCl

O–

POCl2

OPOCl2

+

+

++

+

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Conversion of Alcohols into Alkyl Halides

• 3° alcohols are converted by HCl or HBr at low temperature (Figure 17.7)

• 1° and 2° alcohols are resistant to acid – use SOCl2 or PBr3 by an SN2 mechanism (ether solvent)

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Mechanism 2:

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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 chiral 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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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

• Converts secondary alcohol to ketone

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Oxidation of Primary Alcohols

• Jones’ Reagent: CrO3 in aqueous sulfuric acid. – Oxidizes primary alcohols to carboxylic acids:

All of the oxidations occur via an E2 mechanism.60

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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Oxidation of Secondary Alcohols

• Na2Cr2O7 in aqueous acetic acid is an inexpensive oxidizing agent:

CH3 OHNa2Cr2O7

acetic acidCH3 O

4-tert-Methylcyclohexanol 4-tert-Methylcyclohexanone

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Example 5: Predict the major organic product

K2Cr2O7

acetic acidCl

OH

PCC

CH2Cl2OH

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OH

CrO3

H3O+, acetoneOH

CrO3

H3O+, acetone

OH

KMnO4

H2O H3O+OH

KMnO4

H2O H3O+

OH

Excess Na2Cr2O7

Acetic acid reflux tempOH

Excess Na2Cr2O7

Acetic acid reflux temp

OH

Na2Cr2O7

Acetic acid RTOH

Na2Cr2O7

Acetic acid RT

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

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Preparation and Uses of Phenols

• Industrial process from readily available cumene

• Forms cumene hydroperoxide with oxygen at high temperature

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Laboratory Preparation of Phenols

• From aromatic sulfonic acids by melting with NaOH at high temperature

• Limited to the preparation of alkyl-substituted phenols

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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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