Alcohols, Carbonyls and REDOX
• The Carbonyl Group (Section 12.1)
• Oxidation/Reduction Reactions: Review (Section 12.2)
• Reduction of Carbonyls to Alcohols (Section 12.3)
• Oxidation of Alcohols (Section 12.4)
• Organometallic Compounds (Section 12.5)
• Organolithium and Magnesium Compounds (Section 12.6)
• Reactions of Organolithium/Magnesium Species (Section 12.7)
• Alcohols from Grignard Reactions (Section 12.8)
• Lithium Dialkylcuprates (Section 12.9)
The Carbonyl Functional Group
O
O
R
Carbonyl
O
O
H
R
Aldehyde
R'
Ketone
R
O
OH
Carboxylic
Acid
R
OR'
Carboxylate
Ester
O
120o
R
R
Planar, sp2 Hybridized Carbon
• Carbonyl Features 1 s and 1 p Bond
• Carbonyl Group Quite Polarized (Cd+, Od-)
Resonance Structure for Carbonyl Reflecting Bond Polarization??
General Reactions of Carbonyls
Nucleophilic Addition to Carbonyl Groups:
d
Nu
Nucleophile
Nu
d
O
O
Carbonyl
Addition Product:
TETRAHEDRAL
Oxidation of Alcohols/Reduction of Carbonyls:
O
More
Hydrogen
Content
Oxidation
R
OH
Primary
Alcohol
Reduction R
H
Aldehyde
Less
Hydrogen
Content
Oxidation/Reduction Reactions
• Commonly Termed ‘REDOX’ Reactions
• From General Chemistry, we Will Recall
 Oxidation: Loss of Electrons
 Reduction: Gain of Electrons
• Organic Chemists will Typically use Different Definitions
 Reduction: Increase Hydrogen Content (Decrease Oxygen)
 Oxidation: Decrease Hydrogen Content (Increase Oxygen)
• Oxidizing/Reducing Agents: Usually Inorganic Compounds (M+)
• We will also Recall that in REDOX Reactions:
 Oxidizing Agents get Reduced
 Reducing Agents get Oxidized
Oxidation States of Carbon: Organics
H
CH3
H
CH3
H
C
H
H3C
C
H
H
-4
CH3
C
H
H
CH3
H
-3
C
CH3
H
-2
-1
CH3
H3C
C
CH3
H3 C
0
O
Br
O
O
H 3C
C
C
C
CH3
H3 C
1
H3C
C
CH3
2
H3C
OH
3
O
4
• +1 For More Electronegative, -1 For Less, 0 For Bonded Carbon
Alcohol Synthesis: Carbonyl Reduction
O
[H]
Reduction
R
OMe
O
R
[H]
Reduction
OH
ROH
1o Alcohol
ROH
1o Alcohol
O
[H]
Reduction
R
H
R
[H]
Reduction
Me
Ketones Reduced to
2° Alcohols
ROH
1o Alcohol
OH
O
Carboxylic Acids, Esters,
Aldehydes Reduced to
1° Alcohols
R
Me
2o Alcohol
Several Hydrogen Sources
Are Used In Organic
Reactions: We’ve Already
Seen NaBH4
Reducing Agents: 1° and 2° Alcohols
• Sodium Borohydride: NaBH4
• Lithium Aluminum Hydride: LiAlH4 (LAH)
• H2/Transition Metal Catalyst (z.b. CuO•CuCr2O4)
• NaBH4 and LiAlH4 are Hydride Transfer Agents
• Hydride (H¯) Acts as a Nucleophile
• Carbonyls Have Varying Degrees of Ease of Reduction:
O
O
O
>
R
O
Hardest
O
>
R
OR'
>
R
R'
R
H
Easiest
Selection of a Reducing Agent
• Choice of Reducing Agent Impacts Reaction Products
• For Ketones/Aldehydes Either Reductant Suffices
Carboxylate
Ester
Ketone
Aldehyde
1° Alcohol
1° Alcohol
2° Alcohol
1° Alcohol
NaBH4 No Reaction No Reaction 2° Alcohol
1° Alcohol
LiAlH4
• Carboxylates/Esters Only Reduced by LiAlH4
• For Compounds w/ Multiple Carbonyl F.G.s; Select Based
on Which Group(s) Need to be Reduced
NaBH4/LiAlH4 Reduction Examples
O
OH
OH
1. LAH/Et2O
NaBH4
H2O
2. H2O/H2SO4
OH
NO REACTION
1. LAH/Et2O
NaBH4
H2O
2. H2O/H2SO4
O
OH
O
OH
1. LAH/Et2O
NaBH4
H2O
O
OH
OH
2. H2O/H2SO4
O
OH
OH
Oxidizing Agents in Organic Chemistry
CrO3/H2SO4
N
H
CrO3Cl
H2CrO4
Pyridinium chlorochromate
(PCC)
Chromic Acid
(Jones Reagent)
• PCC Generally a Mild Oxidant (1° Alcohol  Aldehyde)
• Jones Reagent Harsher Oxidant (1° Alcohol  Carboxylic Acid)
• Alcohol Often Dissolved in Acetone While Jones Reagent Added
• Choose Oxidant Based on Desired Carbonyl Functional Group
General Oxidizing Agent Selection
• Just as in Reductions, Oxidation Products Depend on Reagent
• Generally Don’t Oxidize 3° Alcohols (No Texas Carbons)
MeOH
1° Alcohol
2° Alcohol
3° Alcohol
PCC
H2C=O
Aldehyde
Ketone
No
Reaction
Cr6+
H2SO4
HCO2H
Carboxylic
Acid
Ketone
No
Reaction
• PCC Good For Aldehydes From Primary Alchols
• Cr6+/H2SO4 Reagents, KMNO4 Primary  Carboxylic Acids
• Use What You Like For Most Ketones
Oxidation of 1°, 2° Alcohols
O
OH
PCC
H
CH2Cl2, 25 oC
O
OH
H2CrO4
acetone, 35 oC
OH
OH
KMnO4, H2O
NaOH, Heat
O
Oxidation Mechanisms: Chromate Esters
H
Protonation, Followed by Loss
of Water (Combined Here)
H
O
O
H
O
O
HO
Cr
Cr
O
O
O
O
H
H
O
H
H
H2O
O
O +
Cr
OH
O
H
O + H3O
O
Cr
OH
Chromate Ester
O
Organometallic Compounds
• Organic Compounds Containing Carbon—Metal Bonds
• Bonds Range From Ionic to Primarily Covalent
• Ionic C—M Bonds:
 C—Na
 C—K
• Primarily Covalent C—M Bonds:
 C—Pb
 C—Sn
 C—Hg
• Inetermediate C—M Bonds Include C—Mg and C—Li
• Reactivity Increases with Ionic Character of C—M Bond
Organolithium Reagents
Common Solvents for Organolithium Reagents:
O
Diethyl Ether
O
Tetrahydrofuran
Preparation of Organolithium Reagents:
Br
2Li, -10 oC
Et2O
Li
+
LiBr
Butyllithium
(Alkyl Lithium Reagent)
• Reactive, Carbanion-Like Species (React Slowly w/ Ethers)
• Halide Reactivity: RI > RBr > RCl (F Not Often Used)
Grignard Reagents
Preparation of Grignard Reagents:
Br
Mg
Et2O
MgBr
Butylmagnesium Bromide
(Grignard Reagent)
MgBr
Br
Mg
Et2O
Phenylmagnesium Bromide
(Grignard Reagent)
• Reactivity of Halides Same as for Organolithium Reagents
• Generally Exist as Complexes, We’ll Use RMgX for Simplicity
Organometallic Reactions: Notes
• Can Act as Nucleophiles Towards Polarized Carbonyl Groups
• Very Strong Lewis Bases (React with Acidic Protons)
• Basicity Necessitates Dry Conditions (Avoid Reaction w/ H2O)
• Reason For Basicity: Carbanion-Like Behavior (pKa??)
• Strong Enough Bases to Deprotonate Terminal Alkynes (pKa??)
• With No Acidic Protons, Can Do Nucleophilic Substitution
Let’s Look at Some Representative Grignard Reactions
Grignard Reactions: Epoxides
MgBr
MgBr
O
1. Et2O
2. H3O+
OH
O
1. Et2O
2. H3O+
OH
+
+
• Grignard Reagents Nucleophilically Open Epoxides
• Generally Attack Less Substituted Carbon (Steric Hindrance)
• View This as Carbanion Attacking in SN2 Reaction (O L.G.)
Grignard Reactions w/ Carbonyls
• Grignard Reagents React With a Variety of Carbonyls
 Formaldehyde  1° Alcohols
 Higher Aldeydes  2° Alcohols
 Ketones  3° Alcohols
 Ester  3° Alcohols
• Attack of Grignard Generates Alkoxide; Protonate to get OH
Let’s Look at Some Specific Grignard Reactions w/ Carbonyls
Grignard Reactions: Carbonyls
MgBr
O
OH
Et2O
+
H
MgBr
H
Me
O
OH
Et2O
+
H3C
H
Me
Me
MgBr
O
Et2O
+
H3C
CH3
OH
Grignard Reactions: Esters
Me
MgBr
OH
O
Et2O
+
H3C
OCH3
• Grignard Reagents React Twice w/ Esters  3° Alcohols
• Two Alkyl Groups of Alcohol Correspond to Grignard Reagent
• Grignard Reactions Quite Useful in Wide Range of Alcohol
Syntheses (w/ Varying Degrees of Substitution)
Reactions of Organolithium Compounds
• Organolithium Reagents React Similarly to Grignards
• Also Strong Bases, Same Limitations Apply
• More Reactive Species Than Grignard Reagents
• Routine Syntheses: Prefer to use Grignard Reagents
• Sodium Alkynides (Triple Bond Anions) React in Same Manner
w/ Aldehydes and Ketones
Now We’ll Look at One More Organometallic: Lithium
Dialkylcuprates (A Coupling Reagent)
Lithium Dialkylcuprates
Me
I
(CH3)2CuLi
Et2O
CH3Br
2Li, Et2O
2 CH3Li
CuI
(CH3)2CuLi
Me
Br
(CH3)2CuLi
Et2O
Quite Versatile C—C Bond Forming Reaction