ALCOHOLS

Dr. Sheppard

CHEM 2412

Summer 2015

Klein (2nd ed.) sections 13.1, 13.2, 13.3, 13.5, 13.4,

13.6, 13.7, 13.10, 13.9, 13.13

Alcohols• Important in synthesis

• Easily converted to or prepared from other functional groups

• Used as solvents • Especially low molecular weight alcohols

• Types of alcohols:

• Phenols and enols have different reactivity from alcohols

Structure of Alcohols• Hybridization of C?• Bond angle around C?• Hybridization of O?

• Classification as primary, secondary, or tertiary:

Spectroscopy of Alcohols: IR• IR absorptions at 1050 cm-1 and 3300-3600 cm-1

Spectroscopy of Alcohols: NMR• Atoms bonded to O are deshielded• 13C-NMR:

• 1H-NMR: singlet at d2.5-5.0

Spectroscopy of Alcohols: MS• M+ usually small or absent• M-18 comes from loss of water• Ex: 1-butanol

Naming Alcohols (Review)• Acyclic alcohols

1. Parent chain is longest chain containing C bonded to –OH

2. Change suffix from “-e” to “-ol”

3. Number from end closest to –OH• Show location of –OH

4. Name/number substituents

• Cyclic alcohols1. Ring is the parent

2. Number ring so –OH is at carbon 1 and other substituents have lowest possible numbers• You do not need to show the location of the –OH

3. Name/number substituents

Naming Alcohols (Review)• Multiple hydroxyl groups

1. Two –OH groups is a diol; 3 is a triol

2. Two adjacent –OH groups is a glycol

3. Name as acyclic alcohols, except keep the “-e” suffix and add “-diol”

4. Indicate numbers for all –OH groups

• Examples:

OHOH

OH

OH

OH

• Alcohols are polar• Intermolecular forces

• Dipole-dipole and hydrogen bonding

• Boiling points • High; increase with number of carbons; decrease with branching

• Solubility• Low MW soluble in water; decreases as MW increases

Physical Properties of Alcohols

Which molecule in each pair has the higher boiling point?

a)

b)

c)

d)

HO

OH OH

CH3CH2CH2OH CH3CH2CH2CH3

CH3CH2OH CH3CH2CH2OH

OH OH

Acidity/Basicity of Alcohols• Alcohols are weak bases and weak acids• As a base:

• A strong acid is needed to protonate a neutral alcohol

Acidity/Basicity of Alcohols• As an acid:

• A strong base (alkoxide ion) is formed• Methoxide, ethoxide, tert-butoxide, etc.

• Alcohols that are stronger acids yield anions that are more stable or can be more easily solvated

Acidity of Alcohols: Steric Effect• For example, compare

CH3CH2O- and (CH3)3CO-

Sterically accessible; less hindered and more easily solvated

Sterically less accessible; more hindered and less easily solvated

Acidity of Alcohols: Inductive Effect

Acidity of Alcohols: Resonance Effect• Phenols are more acidic than alcohols

• Cyclohexanol vs. phenol• Resonance-stabilized phenoxide anion

• Electron-withdrawing groups make phenols more acidic• Ex: p-nitrophenol pKa = 7.15

• Electron-donating groups make phenols less acidic• Ex: p-aminophenol pKa = 10.46

Chemistry of Alcohols

I. Preparation of Alcohols

II. Reactions of Alcohols

Preparation of Alcohols• From alkyl halides

• Substitution reactions (compete with elimination)

Preparation of Alcohols• From alkenes

1. Acid-catalyzed hydration (Markovnikov, can rearrange)

2. Oxymercuration-reduction (Markovnikov, no rearrangement)

3. Hydroboration-oxidation (anti-Markovnikov, no rearrangement)

Preparation of Alcohols• From alkenes

4. Hydroxylation (yields glycol)

Preparation of Alcohols• From carbonyl compounds

1. Reduction

2. Grignard reaction

Reduction of Carbonyls

• Type of alcohol formed depends on carbonyl

Reduction of Carbonyls• Reducing agent [H] = metal hydride• Hydride (H:-)

• From NaBH4 or LiAlH4

• Mechanism:

Reduction of Carbonyls

• Sodium borohydride (NaBH4)• Selectively reduce aldehydes and ketones• Conditions: H2O, MeOH or EtOH

Reduction of Carbonyls

• Lithium aluminum hydride (LiAlH4 or LAH)• Stronger reducing agent than NaBH4

• Reduces aldehydes and ketones

• Also reduces carboxylic acids and esters (to primary alcohols)

• Conditions: aprotic solvent (ether or THF)• LAH + H2O → H2 (boom!)

Reduction of Carbonyls

• Ester Mechanism:• More detail in Chapter 21

Draw the product of this reduction.

O

O O

1. LAH, THF

2. H3O+

Reduction of Carbonyls• In addition to metal hydrides, carbonyls can be reduced

with H2

• Catalyst = Raney nickel• Or, could use Pd, Pt, Ni with increased temperature and pressure

• Reduce aldehydes and ketones only• Will also reduce double bonds and triple bonds

O

Raney Ni

H2

OH

Summary of Reducing Agents

Functional Group

NaBH4 LiAlH4

H2

Raney NiH2

Pt, Pd, Ni

Aldehyde

Ketone

Carboxylic acid

Ester

C=C, C≡C

What methods can be used to synthesize a primary alcohol?

What starting materials/reagents could be used to synthesize 4-methyl-2-penten-1-ol?

Preparation of Alcohols• From carbonyl compounds

1. Reduction

2. Grignard reaction

The Grignard Reaction• Carbonyl + Grignard reagent → Alcohol

• Carbonyl = aldehyde, ketone, ester, or acid chloride• Grignard reagent = an organometallic reagent (R-Mg-X)• Alcohol = 1°, 2°, or 3° depending on carbonyl

• This is a C-C bond making reaction!

Formation of Grignard Reagent

• R cannot contain acidic hydrogens• Mg oxidized from Mg0 to Mg2+

• Reagents form on metal surface; solvated by ether (Et2O)

• Radical mechanism

(slow)

Reactivity of Grignard Reagent• C-Mg is a polar covalent bond with partial ionic character

• d- makes C nucleophilic (~carbanion)• Will react with d+ of a carbonyl

• Carbon is also basic• Will react with acidic hydrogens

Grignard Reaction Mechanism

1. Nucleophilic Grignard reagent attacks electrophilic carbonyl; new bond formed between R of RMgX and C of C=O

2. Alkoxide ion (a strong base) reacts with acid (usually HCl/H2O or H3O+) to produce alcohol

Grignard Reaction Product• Alcohol produced depends on type of carbonyl reacting• Formaldehyde:

• Aldehyde:

• Ketone:

Grignard with Esters/Acid Chlorides

• Esters and acid chlorides react with TWO equivalents of Grignard reagent1. Ester/acid chloride → ketone

2. Ketone → tertiary alcohol

• Mechanism:

• Product = tertiary alcohol; two alkyl groups are the same

Grignard Reaction Product

Carbonyl Alcohol

Formaldehyde 1°

Aldehyde 2°

Ketone 3°

Ester/acid chloride 3°

Provide starting materials in the boxes below to complete the following reactions:

a)

b)

c)

1. PhMgBr

2. HCl, H2O

2. HCl, H2O

2. HCl, H2O

CH2OH

OH

OH

1. PhMgBr

1. PhMgBr

Show how the following compound can be synthesized from an acid chloride using the Grignard reaction.

OHCH3

How can 2-phenyl-2-butanol be synthesized using the Grignard reaction?

Grignard Reaction Limitations• Grignard reagents cannot react with or be formed from

any molecule containing an acidic hydrogen• O-H, N-H, S-H, -C≡C-H• RMgX will pick up acidic H and “kill” the reagent

• To allow the reaction to occur even with an -OH present in the starting material, we must “protect” the alcohol

Protection of Alcohols• Three-step process

1. Introduce protecting group

2. Carry out reaction

3. Remove protecting group

Protection of Alcohols• Protecting group is chlorotrimethylsilane (TMS-Cl)• Nitrogen base promotes reaction

• SN2-like reaction is allowed with tertiary Si• Less sterically crowded due to longer bonds

• To remove TMS group • React with H3O+ or F- (from TBAF)

Grignard Reaction with Protecting Groups

Chemistry of Alcohols

I. Preparation of Alcohols

II. Reactions of Alcohols