1. Oxidation-Reduction & Organometallic
Chapter 12
Alcohols from
Carbonyl Compounds
Oxidation-Reduction & Organometallic
Compounds
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1. Structure of the Carbonyl Group
Carbonyl compounds
Aldehyde
Ketone
Carboxylic acid
Ester
Amide
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Structure
Carbonyl carbon: sp2 hybridized
Planar structure
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Polarization and resonance structure
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5. 1A. Reactions of Carbonyl Compounds with Nucleophiles
One of the most important reactions of carbonyl compounds is nucleophilic addition to the carbonyl group
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Two important nucleophiles:
Hydride ions (from NaBH4 and LiAlH4)
Carbanions (from RLi and RMgX)
Another important reaction:
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2. Oxidation-Reduction Reactions in Organic Chemistry
Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content
oxygen content
decreases
hydrogen content
increases
carboxylic
acid
aldehyde
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The opposite reaction of reduction is oxidation. Increasing the oxygen content of an organic molecule or decreasing its hydrogen content is oxidation
lowest
oxidation
state
highest
oxidation
state
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Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon
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10. 2A. Oxidation States in Organic Chemistry
Rules
For each C–H (or C–M) bond  -1
For each C–C bond  0
For each C–Z bond  +1
(where M = electropositive element and is equivalent to H, e.g. Li, K, etc.; Z = electronegative heteroatom, e.g. OR, SR, PR2, halogen, etc.)
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Calculate the oxidation state of each carbon based on the number of bonds it is forming to atoms more (or less) electronegative than carbon
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Examples
Bonds to C:
4 to H = (- 1) x 4 = - 4
Total = - 4
Oxidation state of C = - 4
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Examples
Bonds to C:
3 to H = - 3
1 to O = +1
Total = - 2
Oxidation state of C = - 2
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Examples
Bonds to C:
2 to H = - 2
2 to O = +2
Total = 0
Oxidation state of C = 0
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Examples
Bonds to C:
1 to H = - 1
3 to O = +3
Total = +2
Oxidation state of C = +2
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Overall order
oxidation
state
lowest oxidation
state of carbon
highest oxidation
state of carbon
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3. Alcohols by Reduction of Carbonyl Compounds
(1o alcohol)
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18. 3A. Lithium Aluminum Hydride
LiAlH4 (LAH)
Not only nucleophilic, but also very basic
Reacts violently with H2O or acidic protons (e.g. ROH)
Usually reactions run in ethereal solvents (e.g. Et2O, THF)
Reduces all carbonyl groups
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Examples
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Mechanism
Esters are reduced to 1o alcohols
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3B. Sodium Borohydride
NaBH4
less reactive and less basic than LiAlH4
can use protic solvent (e.g. ROH)
reduces only more reactive carbonyl groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids
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Examples
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Mechanism
Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols
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24. 3C. Overall Summary of LiAlH4 and NaBH4 Reactivity
reduced by LiAlH4
reduced by NaBH4
ease of reduction
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25. 3D. Reduction of Alkyl Halides to Hydrocarbons: RX  RH
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4. Oxidation of Alcohols
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29. 4A. A Common Mechanistic Theme
Alcohol oxidation by elimination
A 1° or 2° alcohol reacts with a reagent that installs a leaving group (LG) on the
alcohol oxygen atom
In an elimination step, a base removes a hydrogen from the
alcohol carbon, the bond forms, and the leaving group departs, resulting in the oxidized product
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Aldehyde
Aldehyde
hydrate
Carboxylic
acid
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4B. Swern Oxidation
Swern oxidation of a 1° alcohol to an aldehyde
Swern oxidation of a 2° alcohol to a ketone
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Mechanism of the Swern oxidation
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Mechanism of the Swern oxidation (Cont’d)
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4C. Chromic Acid (H2CrO4) Oxidation
Chromic acid (H2CrO4) usually prepared by [CrO3 or Na2Cr2O7] + aqueous H2SO4
Jones reagent
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Jones oxidation
Reagent: CrO3 + aqueous H2SO4
A Cr(VI) oxidant
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Mechanism of chromate acid oxidations
Formation of the chromate ester
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The oxidation step
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A Chemical Test for Primary and Secondary Alcohols
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4D. Pyridinium Chlorochromate (PCC)
PCC oxidation
Reagent
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PCC oxidation
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4E. Potassium Permanganate (KMnO4)
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5. Organometallic Compounds
Compounds that contain carbon-metal bonds are called organometallic compounds
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6. Preparation of Organolithium & Organomagnesium Compounds
6A. Organolithium Compounds
Preparation of organolithium compounds
Order of reactivity of RX
RI > RBr > RCl
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Example
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6B. Grignard Reagents
Preparation of organomagnesium compounds (Grignard reagents)
Order of reactivity of RX
RI > RBr > RCl
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Example
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7. Reactions of Organolithium and Organomagnesium Compounds
7A. Reactions with Compounds Containing Acidic Hydrogen Atoms
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Grignard reagents and organolithium compounds are very strong bases
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Examples
As base
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Examples
As base
A good method for the preparation
of alkynylmagnesium halides
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51. 7B. Reactions of Grignard Reagents with Epoxides (Oxiranes)
Grignard reagents react as nucleophiles with epoxides (oxiranes), providing convenient synthesis of alcohols
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Via SN2 reaction
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Also works for substituted epoxides
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54. 7C. Reactions of Grignard Reagents with Carbonyl Compounds
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Mechanism
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8. Alcohols from Grignard Reagents
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R, R’ = H (formaldehyde)
1o alcohol
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R = alkyl, R’ = H (higher aldehydes)
2o alcohol
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R, R’ = alkyl (ketone)
3o alcohol
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Reaction with esters
3o alcohol
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Mechanism
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Examples
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Examples
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Examples
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Examples
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66. 8A. How to Plan a Grignard Synthesis
Synthesis of
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Method 1
Retrosynthetic analysis
Synthesis
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Method 2
Retrosynthetic analysis
Synthesis
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Method 3
Retrosynthetic analysis
Synthesis
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70. 8B. Restrictions on the Use of Grignard Reagents
Grignard reagents are useful nucleophiles but they are also very strong bases
It is not possible to prepare a Grignard reagent from a compound that contains any hydrogen more acidic than the hydrogen atoms of an alkane or alkene
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A Grignard reagent cannot be prepared from a compound containing an –OH group, an –NH– group, an –SH group, a –CO2H group, or an –SO3H group
Since Grignard reagents are powerful nucleophiles, we cannot prepare a Grignard reagent from any organic halide that contains a carbonyl, epoxy, nitro, or cyano (–CN) group
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Grignard reagents cannot be prepared in the presence of the following groups because they will react with them:
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73. 8C. The Use of Lithium Reagents
Organolithium reagents have the advantage of being somewhat more reactive than Grignard reagents although they are more difficult to prepare and handle
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74. 8D. The Use of Sodium Alkynides
Preparation of sodium alkynides
Reaction via ketones (or aldehydes)
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9. Protecting Groups
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Retrosynthetic analysis
However
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Need to “protect” the –OH group first
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Synthesis
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