Chapter 8 Chapter 8 of Alcohols and of Alcohols and

PhenolsPhenols

Structure of AlcoholsStructure of Alcohols

Alcohols are simply organic derivatives Alcohols are simply organic derivatives of water formed by replacing one H of of water formed by replacing one H of water with an R group.water with an R group.

All alcohols have the hydroxyl (OH) All alcohols have the hydroxyl (OH) functional groupfunctional group

Classification of AlcoholsClassification of Alcohols Alcohols are classified as primary, secondary, Alcohols are classified as primary, secondary,

tertiary or aromatic depending upon the class of tertiary or aromatic depending upon the class of the alcoholic carbonthe alcoholic carbon

Primary: carbon with –OH (alcoholic carbon) is Primary: carbon with –OH (alcoholic carbon) is bonded to one other carbon.bonded to one other carbon.

Secondary: carbon with –OH is bonded to two Secondary: carbon with –OH is bonded to two other carbons.other carbons.

Tertiary: carbon with –OH is bonded to three other Tertiary: carbon with –OH is bonded to three other carbons.carbons.

Aromatic Alcohol (phenol): -OH is bonded to a Aromatic Alcohol (phenol): -OH is bonded to a benzene ring.benzene ring. =>=>

Classify these:Classify these:

CH3 CH

CH3

CH2OH CH3 C

CH3

CH3

OH

OH

CH3 CH

OH

CH2CH3 =>

IUPAC NomenclatureIUPAC Nomenclature

Find the longest carbon chain Find the longest carbon chain containing the carbon with the -OH containing the carbon with the -OH group.group.

Drop the -e from the alkane name, Drop the -e from the alkane name, add -ol.add -ol.

Number the chain, starting from the Number the chain, starting from the end closest to the -OH group.end closest to the -OH group.

Number and name all substituents.Number and name all substituents. =>=>

Name these:Name these:

CH3 CH

CH3

CH2OH

CH3 C

CH3

CH3

OH

CH3 CH

OH

CH2CH32-methyl-1-propanol

2-methyl-2-propanol

2-butanol

OH

Br CH3

3-bromo-3-methylcyclohexanol =>

Naming DiolsNaming Diols

Two numbers are needed to locate the two Two numbers are needed to locate the two

-OH groups.-OH groups. Use -diol as suffix instead of -ol.Use -diol as suffix instead of -ol.

HO OH

1,6-hexanediol

=>

GlycolsGlycols

1, 2 diols (vicinal diols) are called glycols.1, 2 diols (vicinal diols) are called glycols. Common names for glycols use the name Common names for glycols use the name

of the alkene from which they were made.of the alkene from which they were made.

CH2CH2

OH OH

CH2CH2CH3

OH OH

1,2-ethanediol

ethylene glycol

1,2-propanediol

propylene glycol =>

Naming Phenols (Aromatic Naming Phenols (Aromatic Alcohols)Alcohols)

-OH group is assumed to be on carbon 1.-OH group is assumed to be on carbon 1. For common names of disubstituted phenols, For common names of disubstituted phenols,

use use ortho-ortho- for 1,2; for 1,2; meta- meta- for 1,3; and for 1,3; and para- para- for for 1,4.1,4.

Methyl phenols are cresols.Methyl phenols are cresols.

OH

Cl

3-chlorophenol

meta-chlorophenol

OH

H3C

4-methylphenolpara-cresol =>

Physical PropertiesPhysical Properties

Unusually high boiling points due to Unusually high boiling points due to hydrogen bonding between hydrogen bonding between molecules.molecules.

Small alcohols are miscible in water, Small alcohols are miscible in water, but solubility decreases as the size of but solubility decreases as the size of the alkyl group increases.the alkyl group increases.

=>=>

The High Boiling Points of Alcohols The High Boiling Points of Alcohols and Phenols are due to their ability to and Phenols are due to their ability to

Hydrogen Bond to one anotherHydrogen Bond to one another Alcohols and phenols have much higher Alcohols and phenols have much higher

boiling points than other molecules of boiling points than other molecules of similar Molecular Weightsimilar Molecular Weight

Alcohols Form Hydrogen BondsAlcohols Form Hydrogen Bonds A positively polarized A positively polarized OH hydrogen atom from one molecule OH hydrogen atom from one molecule

is attracted to a lone pair of electrons on a negatively is attracted to a lone pair of electrons on a negatively polarized oxygen atom of another moleculepolarized oxygen atom of another molecule

This produces a force that holds the two molecules togetherThis produces a force that holds the two molecules together These intermolecular attractions are present in solution but These intermolecular attractions are present in solution but

not in the gas phase, thus elevating the boiling point of the not in the gas phase, thus elevating the boiling point of the solutionsolution

Solubility in WaterSolubility in Water

Solubility decreases as the size of the alkyl group increases.

=>

Non-polar

Polar

Alchols and Phenols are Alchols and Phenols are Weak BrWeak Brønsted Acidsønsted Acids

Remember, Bronsted Acids are Proton Donars. Remember, Bronsted Acids are Proton Donars. Alcohols and Phenols can donate a proton to waterAlcohols and Phenols can donate a proton to water

The products are HThe products are H33OO++ and an and an alkoxide anion, alkoxide anion, RORO, or a , or a phenoxide anion, ArOphenoxide anion, ArO

Relative Acidities of Alcohols and Steric EffectsRelative Acidities of Alcohols and Steric Effects Alkyl groups make an alkoxide anion more difficult to be solvated Alkyl groups make an alkoxide anion more difficult to be solvated

and stabilized by water molecules and therefore make its formation and stabilized by water molecules and therefore make its formation less likely and the corresponding acid necessarily weakerless likely and the corresponding acid necessarily weaker

The more easily the alkoxide ion is solvated by water the more The more easily the alkoxide ion is solvated by water the more stable it is and the more its formation is energetically favoredstable it is and the more its formation is energetically favored

More likely to form

Less likely to form

Inductive EffectsInductive Effects

Electron-withdrawing groups make an Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the alcohol a stronger acid by stabilizing the alkoxide anionalkoxide anion

Table of Table of KKaa Values Values

=>

CH3 OH

Generating Alkoxides from AlcoholsGenerating Alkoxides from Alcohols

As weak acids, alcohols react with strong As weak acids, alcohols react with strong bases like sodium or potassium metal to bases like sodium or potassium metal to generate alkoxidesgenerate alkoxides

Alkoxides are bases used as reagents in Alkoxides are bases used as reagents in organic chemistry organic chemistry

Formation of Phenoxide IonFormation of Phenoxide IonPhenol is more acidic than regular alcohols because Phenol is more acidic than regular alcohols because

the phenoxide anion is resonance stabilized. the phenoxide anion is resonance stabilized. Electron withdrawing groups stabilize the Electron withdrawing groups stabilize the phenoxide anion and make phenol more acidicphenoxide anion and make phenol more acidic

Consequently, phenol can be deprotonated by a Consequently, phenol can be deprotonated by a simple hydroxy base.simple hydroxy base.

O H

+ OH

O

+ HOH

pK a = 10pK a = 15.7

=>

Substituted PhenolsSubstituted Phenols Can be more or less acidic than phenol itself. Remember, the acidity of Can be more or less acidic than phenol itself. Remember, the acidity of

any alcohol is determined by the stability of the alkoxide or phenoxide any alcohol is determined by the stability of the alkoxide or phenoxide anion produced. The more stable the anion produced the more acidic the anion produced. The more stable the anion produced the more acidic the alcoholalcohol

An electron-withdrawing substituent makes a phenol more acidic by An electron-withdrawing substituent makes a phenol more acidic by delocalizing the negative charge on the phenoxide aniondelocalizing the negative charge on the phenoxide anion

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

Preparation of Alchols: an Preparation of Alchols: an OverviewOverview

Alcohols are derived from many types of compoundsAlcohols are derived from many types of compounds Also the alcohol hydroxyl can be converted into many other Also the alcohol hydroxyl can be converted into many other

functional groupsfunctional groups This makes alcohols useful in synthesisThis makes alcohols useful in synthesis

Review: Preparation of Alcohols from Review: Preparation of Alcohols from AlkenesAlkenes

Markovnikov and Anti-Mardovnikov Markovnikov and Anti-Mardovnikov hydrationhydration

H2SO4

Alcohols from Reduction Alcohols from Reduction of Carbonyl Compounds of Carbonyl Compounds

Reduction of a carbonyl compound in general Reduction of a carbonyl compound in general gives an alcoholgives an alcohol

Note that organic reduction reactions increase the Note that organic reduction reactions increase the C-H bonds and/or decrease the C-O bondsC-H bonds and/or decrease the C-O bonds

1.H-

2.H+

Reduction of Aldehydes and Reduction of Aldehydes and Ketones Ketones

Aldehydes gives primary alcoholsAldehydes gives primary alcohols Ketones gives secondary alcoholsKetones gives secondary alcohols

1.H-

2.H+

1.H-

2.H+

Reducing agents: Sodium Reducing agents: Sodium Borohydride and Lithium Aluminum Borohydride and Lithium Aluminum

Hydride, Sources of Hydride, Sources of HH-- NaBHNaBH44 is safe, not sensitive to moisture, and it does not is safe, not sensitive to moisture, and it does not

reduce other common functional groupsreduce other common functional groups Lithium aluminum hydride (LiAlHLithium aluminum hydride (LiAlH44) is more powerful, will ) is more powerful, will

reduce species that NaBHreduce species that NaBH44 will not, but is dangerous to use will not, but is dangerous to use Both add the equivalent of “HBoth add the equivalent of “H--” ”

Mechanism of ReductionMechanism of Reduction

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

Reduction of Carboxylic Reduction of Carboxylic Acids and Esters Acids and Esters

Carboxylic acids and esters are reduced to give Carboxylic acids and esters are reduced to give primary alcoholsprimary alcohols

LiAlHLiAlH44 is used because NaBH is used because NaBH44 is not effective is not effective

Sodium BorohydrideSodium Borohydride Hydride ion, HHydride ion, H--, attacks the carbonyl , attacks the carbonyl

carbon, forming an alkoxide ion.carbon, forming an alkoxide ion. Then the alkoxide ion is protonated Then the alkoxide ion is protonated

by dilute acid.by dilute acid. Only reacts with carbonyl of aldehyde Only reacts with carbonyl of aldehyde

or ketone, or ketone, notnot with carbonyls of with carbonyls of esters or carboxylic acids.esters or carboxylic acids.

HC

O

HC

H

OHC

H

OH HH3O+

=>

Lithium Aluminum Lithium Aluminum HydrideHydride

Stronger reducing agent than Stronger reducing agent than sodium borohydride, but dangerous sodium borohydride, but dangerous to work with.to work with.

Converts esters and acids to 1º Converts esters and acids to 1º alcohols.alcohols.

CO

OCH3C

OH H

HH3O+

LAH =>

3030

LiAlHLiAlH4 4 Reactions Reactions

with Esters and Carboxylate with Esters and Carboxylate AnionsAnions

Use two moles of Hydride (HUse two moles of Hydride (H--) reagent.) reagent. The product is a primary alcohol with The product is a primary alcohol with

two hydrogens from hydride reagent.two hydrogens from hydride reagent. Reaction with the first mole of Hydride Reaction with the first mole of Hydride

reagent produces an aldehyde reagent produces an aldehyde intermediate, which reacts with the intermediate, which reacts with the second mole of Hydride second mole of Hydride =>=>

LiAlH4 and Ester – Step 1

• The first hydride (H-) attacks the carbonyl.• Alkoxide ion leaves! ? !

31

C OCH3O

H3C

MgBrR MgBr C

CH3

OCH3

OR

C

CH3

OCH3

OR MgBr C

CH3

RO

+ MgBrOCH3

Aldehyde intermediate =>

H-

H H

H

+ CH3O-

Alkoxide

Second step of reaction• The second hydride reacts with the aldehyde

intermediate to form an alkoxide ion.• Alkoxide ion is protonated with water or dilute

acid.

32

C

CH3

RO

R MgBr + C

CH3

R

OR MgBr

HOH

C

CH3

R

OHR

=>

H- H- H H

H

H

HH

+

Comparison of Comparison of Reducing AgentsReducing Agents

LiAlHLiAlH44 is stronger. is stronger.

LiAlHLiAlH44 reduces more reduces more stable compounds stable compounds which are resistant which are resistant to reduction.to reduction. =>=>

3434

Organometallic ReagentsOrganometallic Reagents

Carbon is bonded to a metal (Mg)Carbon is bonded to a metal (Mg) Carbon is more electronegative than Carbon is more electronegative than

the metal and therefore is nucleophilic the metal and therefore is nucleophilic (partially negative).(partially negative).

It will attack a partially positive carbon.It will attack a partially positive carbon.– C = O in much the same way as the HC = O in much the same way as the H--

A new carbon-carbon bond forms and a A new carbon-carbon bond forms and a more complex alcohol is formed.more complex alcohol is formed. =>=>

3535

Grignard ReagentsGrignard Reagents

Formula R-Mg-X (reacts like R:Formula R-Mg-X (reacts like R:-- ++MgX)MgX) Stabilized by anhydrous etherStabilized by anhydrous ether May be formed from May be formed from anyany halide halide

– primaryprimary– secondarysecondary– tertiarytertiary– vinylvinyl– arylaryl

=>=>

3636

Some Grignard Reagent Some Grignard Reagent FormationsFormations

Br

+ Mgether MgBr

CH3CHCH2CH3

Clether

+ Mg CH3CHCH2CH3

MgCl

CH3C CH2

Br + Mgether

CH3C CH2

MgBr =>

3737

Reaction with CarbonylReaction with Carbonyl

R:R:- - attacks the partially positive carbon attacks the partially positive carbon in the carbonyl.in the carbonyl.

The intermediate is an alkoxide ion.The intermediate is an alkoxide ion. Addition of water or dilute acid Addition of water or dilute acid

protonates the alkoxide to produce an protonates the alkoxide to produce an alcohol.alcohol.

RC O R C O

HOHR C OH

OH=>

3838

Synthesis of 1° AlcoholsSynthesis of 1° Alcohols

Grignard + formaldehyde yields a primary Grignard + formaldehyde yields a primary alcohol with one additional carbon.alcohol with one additional carbon.

C OH

HC

CH3

H3C CH2 C MgBr

H

HH

CH3 CH

CH3

CH2 CH2 C

H

H

O MgBr

HOHCH3 CH

CH3

CH2 CH2 C

H

H

O H

=>

3939

Synthesis of 2º AlcoholsSynthesis of 2º Alcohols

Grignard + aldehyde yields a secondary Grignard + aldehyde yields a secondary alcohol.alcohol.

MgBrCH3 CH

CH3

CH2 CH2 C

CH3

H

OC

CH3

H3C CH2 C MgBr

H

HH

C OH

H3C

CH3 CH

CH3

CH2 CH2 C

CH3

H

O HHOH

=>

4040

Synthesis of 3º AlcoholsSynthesis of 3º Alcohols

Grignard + ketone yields a tertiary Grignard + ketone yields a tertiary alcohol.alcohol.

MgBrCH3 CH

CH3

CH2 CH2 C

CH3

CH3

OC

CH3

H3C CH2 C MgBr

H

HH

C OH3C

H3C

CH3 CH

CH3

CH2 CH2 C

CH3

CH3

O HHOH

=>

4141

How would you synthesize How would you synthesize these using a Grignard these using a Grignard

Reagent…Reagent…CH3CH2CHCH2CH2CH3

OH CH2OH

OH

CH3C

OH

CH2CH3

CH3 =>

4242

Grignard Reactions Grignard Reactions with Esterswith Esters

Use two moles of Grignard attack. Just as Use two moles of Grignard attack. Just as two moles of Hydride attacked an Ester.two moles of Hydride attacked an Ester.

The product is a tertiary alcohol with The product is a tertiary alcohol with two identical alkyl groups ( from Grignard).two identical alkyl groups ( from Grignard).

Reaction with one mole of Grignard Reaction with one mole of Grignard reagent produces a ketone intermediate, reagent produces a ketone intermediate, which reacts with the second mole of which reacts with the second mole of Grignard reagent.Grignard reagent. => =>

4343

Grignard and Ester – First StepGrignard and Ester – First Step

Grignard attacks the carbonyl.Grignard attacks the carbonyl. Alkoxide ion leaves! ? !Alkoxide ion leaves! ? !

C OCH3O

H3C

MgBrR MgBr C

CH3

OCH3

OR

C

CH3

OCH3

OR MgBr C

CH3

RO

+ MgBrOCH3

Ketone intermediate =>

4444

Second step of reactionSecond step of reaction

Second mole of Grignard reacts with the ketone Second mole of Grignard reacts with the ketone intermediate to form an alkoxide ion.intermediate to form an alkoxide ion.

Alkoxide ion is protonated with dilute acid.Alkoxide ion is protonated with dilute acid.

C

CH3

RO

R MgBr + C

CH3

R

OR MgBr

HOH

C

CH3

R

OHR

=>

4545

How would you How would you synthesize...synthesize...

CH3CH2CCH3

OH

CH3

C

OH

CH3

Using an ester.Using an ester.

CH3CH2CHCH2CH3

OH

=>

Some Reactions of Alcohols Some Reactions of Alcohols

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

Dehydration of Alcohols to Yield Dehydration of Alcohols to Yield Alkenes Alkenes

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

Specific reagents are neededSpecific reagents are needed

Acid- Catalyzed DehydrationAcid- Catalyzed Dehydration Tertiary alcohols are readily dehydrated with acidTertiary alcohols are readily dehydrated with acid Secondary alcohols require more severe conditions (75% Secondary alcohols require more severe conditions (75%

HH22SOSO44, 100°C) - sensitive molecules don't survive, 100°C) - sensitive molecules don't survive Primary alcohols require very harsh conditions – Primary alcohols require very harsh conditions –

impracticalimpractical Reactivity order is the result of the stability order of the Reactivity order is the result of the stability order of the

carbocation intermediatecarbocation intermediate

4949

Dehydration with POClDehydration with POCl33 Phosphorus oxychloride in the amine Phosphorus oxychloride in the amine

solvent pyridine can lead to solvent pyridine can lead to dehydration of secondary and tertiary dehydration of secondary and tertiary alcohols at low temperaturesalcohols at low temperatures

5050

Conversion of Alcohols into Conversion of Alcohols into Alkyl HalidesAlkyl Halides

33°° alcohols are converted by HCl or HBr alcohols are converted by HCl or HBr at low temperature (Figure 17.7)at low temperature (Figure 17.7)

11° and 2 ° ° and 2 ° alcohols are resistant to acid alcohols are resistant to acid – use SOCl– use SOCl22 or PBr or PBr33 by an S by an SNN2 mechanism2 mechanism

Oxidation of AlcoholsOxidation of Alcohols This can be accomplished by a wide range of inorganic oxidizing agents, such as This can be accomplished by a wide range of inorganic oxidizing agents, such as

KMnOKMnO44, CrO, CrO33, and Na, and Na22CrCr22OO77

Remember oxidation in Organic Chem refers to any reaction that adds bonds from Remember oxidation in Organic Chem refers to any reaction that adds bonds from carbon to oxygen and/or removes bonds from carbon to hydrogencarbon to oxygen and/or removes bonds from carbon to hydrogen

Oxidation of Primary Oxidation of Primary AlcoholsAlcohols

To aldehyde: pyridinium chlorochromate To aldehyde: pyridinium chlorochromate (PCC) in dichloromethane(PCC) in dichloromethane

Other reagents produce carboxylic acidsOther reagents produce carboxylic acids

Oxidation of Secondary Oxidation of Secondary AlcoholsAlcohols

Effective with inexpensive reagents Effective with inexpensive reagents such as Nasuch as Na22CrCr22OO77 in acetic acid or CrO in acetic acid or CrO33 in Hin H22SOSO44 (Jones Reagent) (Jones Reagent)

Laboratory Preparation of Laboratory Preparation of PhenolsPhenols

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

Limited to the preparation of alkyl-Limited to the preparation of alkyl-substituted phenolssubstituted phenols

Reactions of PhenolsReactions of Phenols Phenols take part in electrophilic Phenols take part in electrophilic

aromatic substitution reactions.aromatic substitution reactions. The OH group is an ortho para The OH group is an ortho para

activating group so phenol readily activating group so phenol readily substitute the following in the ortho substitute the following in the ortho and para positions:and para positions:– Br using BrBr using Br22/FeBr/FeBr33

– NONO22 using HNO using HNO33/H/H22SOSO44

– SOSO33H using SOH using SO33/H2SO/H2SO44