alcohols, carbonyls and redox the carbonyl group (section 12.1) oxidation/reduction reactions:...
TRANSCRIPT
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
RR
120o
O O
HR
O
R'R
O
OHR
O
OR'R
Carbonyl Aldehyde Ketone CarboxylicAcid
CarboxylateEster
Planar, sp2 Hybridized Carbon
• Carbonyl Features 1 and 1 Bond
• Carbonyl Group Quite Polarized (C+, O-)
Resonance Structure for Carbonyl Reflecting Bond Polarization??
General Reactions of Carbonyls
Carbonyl
ONu
Nucleophile
Nu
O
Addition Product:TETRAHEDRAL
Nucleophilic Addition to Carbonyl Groups:
Oxidation of Alcohols/Reduction of Carbonyls:
R OHR H
O
PrimaryAlcohol
Aldehyde
Oxidation
Reduction
LessHydrogenContent
MoreHydrogenContent
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
• +1 For More Electronegative, -1 For Less, 0 For Bonded Carbon
H
CHH
HCH3
CHH
HCH3
CCH3H
HCH3
CCH3H
H3C
CH3
CCH3H3C
H3C
Br
CCH3H3C
H3CO
CCH3H3C
O
COHH3C
O
C
O
-4 -3 -2 -1
0
1 2 3 4
Alcohol Synthesis: Carbonyl ReductionO
OMeR
O
OHR
O
HR
O
MeR
[H]
Reduction
[H]
Reduction
[H]
Reduction
[H]
Reduction
ROH
ROH
ROH
OH
MeR
1o Alcohol
1o Alcohol
1o Alcohol
2o Alcohol
Carboxylic Acids, Esters,Aldehydes Reduced to
1° Alcohols
Ketones Reduced to2° Alcohols
Several Hydrogen SourcesAre Used In Organic
Reactions: We’ve AlreadySeen 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
OR'R
O
OR
O
HR
O
R'R
> > >
Hardest Easiest
Selection of a Reducing Agent
Carboxylate Ester Ketone Aldehyde
LiAlH4 1° Alcohol 1° Alcohol 2° Alcohol 1° Alcohol
NaBH4 No Reaction No Reaction 2° Alcohol 1° Alcohol
• Choice of Reducing Agent Impacts Reaction Products
• For Ketones/Aldehydes Either Reductant Suffices
• Carboxylates/Esters Only Reduced by LiAlH4
• For Compounds w/ Multiple Carbonyl F.G.s; Select Basedon Which Group(s) Need to be Reduced
NaBH4/LiAlH4 Reduction ExamplesO
1. LAH/Et2O
2. H2O/H2SO4
NaBH4
H2O
OHOH
OH
O
1. LAH/Et2O
2. H2O/H2SO4
NaBH4
H2ONO REACTION
OH
O
OHO
1. LAH/Et2O
2. H2O/H2SO4
OH
OH
NaBH4
H2O
OH
OHO
Oxidizing Agents in Organic Chemistry
• 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
N H CrO3Cl
Pyridinium chlorochromate(PCC)
H2CrO4
Chromic Acid(Jones Reagent)
CrO3/H2SO4
General Oxidizing Agent Selection
MeOH 1° Alcohol 2° Alcohol 3° Alcohol
PCC H2C=O Aldehyde KetoneNo
Reaction
Cr6+
H2SO4
HCO2HCarboxylic
AcidKetone
No Reaction
• Just as in Reductions, Oxidation Products Depend on Reagent
• Generally Don’t Oxidize 3° Alcohols (No Texas Carbons)
• 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
OH PCC H
O
CH2Cl2, 25 oC
OHH2CrO4
acetone, 35 oC
O
OH KMnO4, H2O
NaOH, Heat
OH
O
Oxidation Mechanisms: Chromate Esters
O
Cr O
O
HO
O
H H
H
Cr
O
O
OO
O
HH
H
H
Cr
O
O
OH
O
H
H2O
Protonation, Followed by Lossof Water (Combined Here)
Chromate Ester
O +
O
Cr
OH
O + H3O
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
O
ODiethyl Ether Tetrahydrofuran
Br 2Li, -10 oC
Et2O
Li+ LiBr
Butyllithium(Alkyl Lithium Reagent)
Common Solvents for Organolithium Reagents:
Preparation of Organolithium Reagents:
• Reactive, Carbanion-Like Species (React Slowly w/ Ethers)
• Halide Reactivity: RI > RBr > RCl (F Not Often Used)
Grignard Reagents
BrEt2O
MgBr
Butylmagnesium Bromide(Grignard Reagent)
Preparation of Grignard Reagents:
Mg
Et2O
Mg
Br MgBr
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
MgBrO
+1. Et2O
2. H3O+OH
MgBrO
+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
Let’s Look at Some Specific 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
Grignard Reactions: Carbonyls
MgBr
H
O
H
+
MgBr
H3C
O
H
+
MgBr
H3C
O
CH3
+
Et2O
Et2O
Et2O
OH
OH
OH
Me
MeMe
Grignard Reactions: Esters
MgBr
H3C
O
OCH3
+Et2O
Me OH
• 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 AlcoholSyntheses (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 Mannerw/ Aldehydes and Ketones
Now We’ll Look at One More Organometallic: LithiumDialkylcuprates (A Coupling Reagent)
Lithium DialkylcupratesI
(CH3)2CuLi
Et2O
Me
CH3Br2Li, Et2O
2 CH3Li CuI (CH3)2CuLi
Br
(CH3)2CuLi
Et2O
Me
Quite Versatile C—C Bond Forming Reaction