Chapter 12: Alcohols

Question 1

Average pKa for alcohols

Answer 1

15−18

Question 2

Factors affecting acidity of alcohols and phenols

Answer 2

1. Resonance- phenols are more acidic (pKa = 10) than alcohols because they are resonance stabalized
2. Induction- a conjugate base that is resonance stabilized by the electron withdrawling effects of nearby atoms will be more stable
3. Solvation effects- a smaller alcohol such as ethanol will be better solcated and will be more stable than a larger alcohol such as tert-butanol (pKa 16 vs. 18)

Question 3

Preparation of alcohols via substitution

Answer 3

Alcohols can be prepared by substitution reactions in which a leaving group is replaced by a hydroxyl group

A primary substrate will require S_N2 conditions; a strong nucleophile (NaOH)

A tertiary substrate will require S_N1 conditions; a weak nucleophile (H₂O)

A secondary substrate is not effective for preparing a secondary alcohol

Question 4

Reagents for deprotonating an alcohol

Answer 4

Question 5

Three methods to produce an alcohol from an alkene via addition

Answer 5

Question 6

Preparing alcohols via reduction

Answer 6

Reagents

H₂ & Pt, Pd, or Ni
Catalytic hydrogenation does NOT selectively reduce carbonyl groups; will also reduce C=C bonds present in molecule

or

NaBH₄ (sodium borohydride) & EtOH, MeOH, or H₂O
NaBH₄ serves as a hydride delivery device and the solvent functions as a proton source; results in a racemic mixture if a chiral center is present

or

1. LiAlH₄ (lithium aluminum hydride)
2. H₃O⁺
   LiAlH₄ serves as a hydride delivery device, a proton source is subsequently added in a work-up step; results in a racemic mixture

• LiAlH₄ can also reduce carboxylic acids and esters

Question 7

Preparation of diols

Answer 7

Diols are compounds with TWO hydroxyl groups

Question 8

Gringard Reagents

Answer 8

Reagents

1. RMgX
2. H₃O⁺

Mechanism

A Grignard reagent is formed by the reaction between an alkyl halide and magnesium characterized by a C−Mg bond; acts as a nucleophile and attacks a carbonyl carbon

CANNOT be used in the presence of a mildy acidic proton as it will just deprotonate the substrate; NOT compatible with carboxylic acids

Regeoselectivity

Attaches the R group to the carbonyl carbon; subsequent workup protonates the carbonyl oxygen creating a hydroxyl group

Stereospecificity

Nuclephilic attack can occur form either side; forms a mixture of enantiomers when a chiral center is present

Question 9

Protection of Alcohols

Answer 9

Reagents

1. TMSCl & Et₃N (triethylamine)
2. TBAF

Mechanism

Allow Grignard reaction to be performed in the presence of acidic protons by replacing them with a protecting group which can subsequently be removed and converted back to its initial group

Question 10

S_N1 Reactions

Alcohols

Answer 10

Reagents

HX

Mechanism

A tertiary alcohol will undergo a substitution reaction when treated with a halogen halide; not effective for primary or secondary alcohols; results in a mixture of enatiomers

Question 11

S_N2 Addition of Bromine

Alcohols

Answer 11

Reagents

HBr

or

1. TsCl (toluenesulfonyl chloride) & py (pyridine)
2. NaBr

or

PBr₃ (phosphorus tribromide)

Mechanism

Occur via “backside attack” leading to inversion of configuration

Question 12

S_N2 Addition of Chlorine

Alcohols

Answer 12

Reagents

HCl and ZnCl₂
Due to its ionic nature can only be used with alcohols that are water-soluble- alcohols with less than eight carbon atoms

or

SOCl₂ (thionyl chloride) & py (pyridine)

or

1. TsCl (toluenesulfonyl chloride) & py
2. NaCl

Mechanism

Occur via “backside attack” leading to inversion of configuration

Question 13

Elimination Reactions

Alcohols

Answer 13

Reagents

conc H₂SO₄ & heat
ONLY works for tertiary alcohols; favors the more substituted Zaitsev product

or

1. TsCl (toluenesulfonyl chloride) & py (pyridine)
2. Strong base

• Choice of base determines Hofmann vs. Zaitsev product

Question 14

Primary Alcohol Oxidation

Answer 14

Carboxylic Acid as the Product

Na₂Cr₂O₇ (sodium dichromate) & H₂SO₄/H₂O

or

xs CrO₃ (chromium trioxide) & H₃O⁺/acetone

Aldehyde as the Product

PCC & CH₂Cl₂ (dichloromethane)

or

Swern oxidation
1. DMSO & (COCl)₂ (oxalyl chloride)
2. Et₃N (triethylamine)

or

Des-Martin periodinane (DMP) oxidation
DMP and CH₂Cl₂

Question 15

Secondary Alcohol Oxidation

Answer 15

Reagents
All processes reduce the secondary alcohol to a ketone

Na₂Cr₂O₇ (sodium dichromate) & H₂SO₄/H₂O

or

xs CrO₃ (chromium trioxide) & H₃O⁺/acetone

or

PCC & CH₂Cl₂ (dichloromethane)

or

Swern oxidation
1. DMSO & (COCl)₂ (oxalyl chloride)
2. Et₃N (triethylamine)

or

Des-Martin periodinane (DMP) oxidation
DMP & CH₂Cl₂ (dichloromethane)

Question 16

Swern Oxidation

Alcohol

Answer 16

Reagents

1. DMSO & (COCl)₂ (oxalyl chloride)
2. Et₃N (triethylamine)

Mechanism

Converts a primary alcohol to an aldehyde

Converts a secondary alcohol to a ketone

Question 17

Des-Martin periodinane (DMP) oxidation

Alcohol

Answer 17

Reagents

DMP and CH₂Cl₂ (dichloromethane)

Mechanism

Converts a primary alcohol to an aldehyde

Converts a secondary alcohol to a ketone

Question 18

Oxidation of Phenol

Answer 18

Reagents

Na₂Cr₂O₇ (sodium dichromate) & H₂SO₄/H₂O

or

xs CrO₃ (chromium trioxide) & H₃O⁺/acetone

Mechanism

Although there is no alpha proton, phenol still undergos oxidation to form a benzoquinone