Industrial Organic Chemistry

Chapter 17.

Alcohol and Phenol

Instructor: Prof. Junhwan Choi

 Introduction
• Alcohol: compounds that have bonded to a saturated sp3-carbon.
• Enols vinylic sp2-carbon (Chapt. 22).

• Methanol

2 3 2
 Introduction
• Ethanol -

• Phenol
as adhesives and antiseptics.
 17-1. Naming Alcohols and Phenols
• primary (1°), secondary (2° tertiary (3°
on the number of organic groups bonded to the hydroxyl-bearing carbon.

• Rule 1. Select the longest carbon chain containing the hydroxyl group.
Replace the –e –ol.
• Rule 2 the end nearer the hydroxyl
group.
• Rule 3. Number the substituents according to their position on the chain,
alphabetical order.
 17-1. Naming Alcohols and Phenols

• : –phenol –benzene.
 17-2. Properties of Alcohols and Phenols
• The tetrahedral value (108.5 ° in
sp3-
• Alcohol and phenol have higher boiling points hydrogen bonding:
1-
1-propanol have higher boiling point (97 °C)
° °
 17-2. Properties of Alcohols and Phenols
• As weak bases protonated

2 .
+

• As weak acids, alcohols and phenols donate a proton to water

alkoxide ion, RO phenoxide ion ArO .
 17-2. Properties of Alcohols and Phenols
• Recall : Ka and pKa.

• Ka pKa.
• Ka pKa.

• alkoxide ion is solvated by water, the more

stable it is, the more its formation is energetically favored, and the greater
the acidity
 17-2. Properties of Alcohols and Phenols
• Acidity of alcohol

• Steric effect:
hindered alkoxide ion (tert-butyl
alcohol)
is less stable (less acidic).
 17-2. Properties of Alcohols and Phenols
• Acidity of alcohol

• Inductive effects: Electron-

withdrawing
substituents stabilize an alkoxide ion

volume, thus making the alcohol

more acidic.
 17-2. Properties of Alcohols and Phenols
• Because alcohols are weak
acids

react to a limited extent

.

• alcohols react
with strong bases such as
),

2) and
Grignard reagents (RMgX).
 17-2. Properties of Alcohols and Phenols
• Phenols are a million times more
acidic than alcohols because the
-

• Delocalization of the negative

charge
increased
stability of phenoxide anion
 17-2. Properties of Alcohols and Phenols
• an electron-withdrawing substituent are more acidic because

• -
noticeable in phenols with nitro group at the ortho or para position.
 17-2. Properties of Alcohols and Phenols
• p-

• the substituent it is electron-

donating or electron-withdrawing.
• -
 17-2. Properties of Alcohols and Phenols
• p-

• electron-withdrawing, thus p-hydroxybenzaldehyde is

more acidic (pKa = 7.9) than phenol (pKa = 9.89).
 17-3. Preparation of Alcohol: A Review
• alkene, alkyl
halides, ketones and aldehydes
 17-3. Preparation of Alcohol: A Review
• Alcohols from alkene

• -Markovnikov hydration product)

demercuration (Markovnikov hydration product)
 17-3. Preparation of Alcohol: A Review
• 1,2-Diols OsO4 3

acid-catalyzed hydrolysis of an epoxide.

 17-4. Alcohols from Carbonyl Compounds: Reduction
•
reduction of a carbonyl compound adds hydrogens to a C=O bond
an alcohol.
• aldehydes, ketones,
carboxylic acids and esters.
• An acidic proton(s).
 17-4. Alcohols from Carbonyl Compounds: Reduction
Reduction of Aldehydes and Ketones
• Aldehydes primary alcohols, and ketones
secondary alcohols.

• Reducing agents 4) –

4) –
 17-4. Alcohols from Carbonyl Compounds: Reduction
• Mechanism: )
electrophilic carbon atom
 17-4. Alcohols from Carbonyl Compounds: Reduction
Reduction of Carboxylic Acids and Esters
• Carboxylic acids and esters primary alcohols.

• 4 esters very slowly and does not reduce carboxylic acid at all.
• more

4.
 17-4. Alcohols from Carbonyl Compounds: Reduction
• Carboxylic acid and ester reductions: two hydrogens become bonded to the
Aldehyde and ketone reductions: one hydrogen
atom
 17-4. Alcohols from Carbonyl Compounds
•

• primary, secondary or tertiary.

• Primary alcohol aldehyde, ester carboxylic acid.
• Secondary alcohol ketone.
• Tertiary alcohol: can not prepared
 17-4. Alcohols from Carbonyl Compounds
(a) secondary alcohol (reduction of a ketone

4 4 can be used.

(b) primary alcohol (reduction of an aldehyde, ester or

carboxylic acid 4
17-5. Alcohols from Carbonyl Compounds: Grignard Reaction
• Grignard reagents (RMgX)

•
Grignard reaction involves addition of a carbanion nucleophile
(R: +MgX).

• alcohol synthesis.
• An acidic proton(s).
17-5. Alcohols from Carbonyl Compounds: Grignard Reaction
• Grignard reagents 2C=O primary alcohols,
with aldehydes to secondary alcohols, with ketones to tertiary alcohols.
17-5. Alcohols from Carbonyl Compounds: Grignard Reaction
•
(two of the substituents

• Carboxylic acids do not

• The acidic carboxyl hydrogen basic Grignard reagent
17-5. Alcohols from Carbonyl Compounds: Grignard Reaction
• Mechanism nucleophilic carbanions (:R ) and the
alkoxide is protonated 3
+.
17-5. Alcohols from Carbonyl Compounds: Grignard Reaction
• can not other reactive
functional group
• an alkyl halide as well as a ketone, carboxylic
acid, alcohol, or amine can not
 17-5. Alcohols from Carbonyl Compounds
•
- -2-

• 2- -2-butanol has a methyl group, an ethyl group and a phenyl group

• 2- -2-butanol is a tertiary alcohol ketone

• Grignard reagent with one functional

group and ketones with the other two functional groups.
 17-5. Alcohols from Carbonyl Compounds
•
- -2-
 17-5. Alcohols from Carbonyl Compounds
•
- -2-

• 2- -2-pentanol has two methyl group, and one propyl group attached to

• 2- -2- ketone ester.

 17-5. Alcohols from Carbonyl Compounds
•
- -2-
 17-6. Reactions of Alcohols
• Recall: SN2 and SN

• SN2: substitution, nucleophilic, • SN1: substitution, nucleophilic,

nd ) st )
 17-6. Reactions of Alcohols
•

• •
 17-6. Reactions of Alcohols

• Tertiary alcohols SN1 mechanism.

• Acid protonates the hydroxyl oxygen
carbocation is generated, and the cation reacts with nucleophilic halide ion
 17-6. Reactions of Alcohols
• Primary and secondary SOCl2 and PBr3 SN2 mechanism.
•
• 2 3 a much better
leaving group, a 2).

• expelled by backside nucleophilic substitution.

 17-6. Reactions of Alcohols
Conversion of Alcohols into Tosylates
• Alcohols react with p- tosyl chloride, p-TosCl) to
alkyl tosylates, ROTos.
•
no change of configuration

• alkyl tosylates behave like alkyl halides N1 and

SN
 17-6. Reactions of Alcohols
• Tosylates in SN2 reaction: stereochemistry
• The SN via an alkyl halide two
inversions the same stereochemistry.
• The SN via a tosylate one inversion:
opposite stereochemistry.
 17-6. Reactions of Alcohols
Dehydration of Alcohols to Alkenes
•
• Tertiary alcohols are dehydrated acid-catalyzed reactions.

'
치란에 가장

N
않은 알켄켄
• The more stable alkene
 17-6. Reactions of Alcohols
• Protonation unimolecular loss of water
carbocation loss of a proton

• Tertiary alcohols react fastest

because a stabilized, tertiary
carbocation intermediates

2 4, 100 °C).
 17-6. Reactions of Alcohols
• mild, basic conditions.

• Phosphorus oxychloride
(POCl3) in the basic amine
solvent pyridine

2), a good leaving

group. Pyridine is solvent
and the base that removes
a neighboring proton.
 17-6. Reactions of Alcohols
•

3
 17-6. Reactions of Alcohols
•

•
 17-6. Reactions of Alcohols
Conversion of Alcohols into Esters
• Alcohols react with carboxylic acids

• The reactivity of the carboxylic acid a

carboxylic acid chloride
 17-7. Oxidation of Alcohols
• oxidation carbonyl compounds:

• Primary alcohols aldehydes carboxylic acids.

• Secondary alcohols ketones.
• Tertiary alcohols: do not
 17-7. Oxidation of Alcohols
• oxidizing agents, including KMnO4, CrO3 and Na2Cr2O7
oxidation of alcohols.
• Primary aldehydes carboxylic acids.
• aldehyde - is used.
 17-7. Oxidation of Alcohols
• E2 reaction.
• a substitution reaction
between the alcohol and the I (V) reagent periodinane
intermediate expulsion of reduced I (III) as the leaving group.
 17-7. Oxidation of Alcohols
• commonly used oxidizing agents (CrO3)
directly to carboxylic acids: an aldehyde is involved as an intermediate but
can not be isolated because it is oxidized too rapidly.

• 3

a chromate intermediate repulsion of a reduced Cr (IV)

species.
 17-7. Oxidation of Alcohols
• Secondary alcohols ketones.
 17-7. Oxidation of Alcohols
•

3 -

(a) 1- (b) 2-
 17-7. Oxidation of Alcohols
•

3 -

(a) 1- (b) 2-
 17-8. Protection of Alcohols
• can not a halo alcohol because the
in the
same molecule.

• Protecting
protecting group

(3) removing
 17-8. Protection of Alcohols
• a chlorotrialkylsilane 3

trialkylsilyl 3.

• A base alkoxide anion

by-product
 17-8. Protection of Alcohols
• - SN2-like reaction of the alkoxide ion on the
silicon atom loss of the leaving chloride anion.
• tertiary center -substituted silicon atom).
• longer bond
substituents attached to silicon thus offer less steric hinderance to reaction.
 17-8. Protection of Alcohols
• A trimethylsilyl (TMS) ethers unreactive

• aqueous acid fluoride ion to generate the

alcohol
 17-8. Protection of Alcohols
• a halo alcohol in a Grignard reaction
a protection
 17-9. Phenols and Their Uses
• isopropylbenzene called cumene.
• benzylic oxidation to
cumene hydroperoxide phenol and acetone
acid.
 17-9. Phenols and Their Uses
Reaction mechanism
•
• Shift of the phenyl group from carbon
to oxygen with simultaneous loss of
water
• Readdition
(called a hemiacetal: a compound that
contains and
group bonded to the same carbon).
• breaks down to
phenol and acetone.
 17-10. Reactions of Phenols
Electrophilic Aromatic Substitution Reactions
• ortho- and para-directing activator.
• highly reactive for electrophilic substitution
-
 17-10. Reactions of Phenols
Oxidation of Phenols: Quinones
• no
hydrogen atom on the hydroxyl-bearing carbon in phenols).
• Oxidation of a phenol - -1,4-dione (quinone) with
Na2 2 7
 17-10. Reactions of Phenols
• Quinones .
• Quinones reduced to hydroquinones (p-

4 and SnCl2) and hydroquinones

reoxidized back to quinones 2 2 7.

•
 Summary of Chapter 17
•

Methods for alcohol synthesis: from carbonyl compounds

• Aldehydes, esters and carboxylic acids 4: mild,

4 primary alcohols. Ketones

secondary alcohols.
• Grignard reagents, RMgX
formaldehyde primary alcohol, addition to an
aldehydes secondary alcohol and addition to a ketone ester
a tertiary alcohol.
• can not alkyl halides that contain reactive
group protecting the interfering functional
group
 Summary of Chapter 17
Reactions of alcohols
• alkenes 3).

• alkyl halides 3 2).

• alkoxide anions.

Oxidation of alcohols
• carbonyl compounds. Primary alcohols
aldehydes carboxylic acids. Secondary alcohols ketones.
Tertiary alcohols not normally oxidized.

Phenols
• more acidic resonance-stabilized
electron-withdrawing group increases phenol acidity.
• quinones
hydroquinones.