Ch. 12 - 1

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Chapter 12

• Alcohols from
• Carbonyl Compounds
• Oxidation-Reduction Organometallic
• Compounds

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1. Structure of the Carbonyl Group

• Carbonyl compounds

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• Structure

• Carbonyl carbon sp2 hybridized
• Planar structure

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• Polarity and resonance structure

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1A. Reactions of Carbonyl Compoundswith
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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1. Oxidation-Reduction Reactions inOrganic 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 on organic
  molecule or decreasing its hydrogen content is
  oxidation.

lowest oxidation state
highest oxidation state other than CO2
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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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2A. Oxidation States in Organic Chemistry

• Rules
• For each CH (or CM) bond ? -1
• For each CC bond ? 0
• For each CZ 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.).
• The oxidation state of each carbon is based on
  the number of bonds it forms 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 Or as indicated in
class, the more electronegative atom controls
the shared electrons. Here C controls 8 es.
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• Examples

Bonds to C
3 to H - 3
1 to O 1
Total - 2
Oxidation state of C - 2 Here C controls 6 es
compared to its 4 valence es.
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• Examples

Bonds to C
2 to H - 2
2 to O 2
Total 0
Oxidation state of C 0 Here C controls 4 es
which equals its of valence es.
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• Examples

Bonds to C
1 to H - 1
3 to O 3
Total 2
Oxidation state of C 2 Here C controls 2 es
compared to its 4 valence es.
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• Overall order of oxidation states of C

oxidation state
lowest oxidation state of carbon
highest oxidation state of carbon
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1. Alcohols by Reduction of Carbonyl Compounds

(1o alcohol)
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3A. Lithium Aluminum Hydride

• LiAlH4 (LAH)
• Not only nucleophilic, but also very basic.
• React violently with H2O or acidic protons (e.g.
  ROH).
• Usually reactions run in ethereal solvents (e.g.
  dry Et2O or THF).
• Reduces all carbonyl groups and requires two
  separate steps.

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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) separate
  acidification is not needed.
• 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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3C. Overall Summary of LiAlH4 and NaBH4
Reactivity
reduced by LiAlH4
reduced by NaBH4
ease of reduction
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1. Oxidation of Alcohols

4A. Oxidation of Primary Alcohols to Aldehydes

• The oxidation of aldehydes to carboxylic acids in
  aqueous solutions is easier than oxidation of 1o
  alcohols to aldehydes.
• Therefore, it is difficult to stop the oxidation
  of a 1o alcohol to the aldehyde stage unless
  specialized reagents are used.

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• PCC oxidation (mild oxidant)

Reagent
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• PCC oxidation

1o
2o
3o
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4B. Oxidation of Primary Alcohols toCarboxylic
Acids

• Chromic acid (H2CrO4) usually prepared by

Jones reagent
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• Jones oxidation
• Reagent CrO3 H2SO4
• A Cr(VI) oxidant

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4D. Mechanism of Chromate Oxidations
Formation of the Chromate Ester intermediate
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• The oxidation step

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4E. A Chemical Test for Primary andSecondary
Alcohols
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4F. Spectroscopic Evidence for Alcohols

• Alcohols give rise to broad O-H stretching
  absorptions from 3200 to 3600 cm-1 in IR spectra.
• The alcohol hydroxyl hydrogen typically produces
  a broad 1H NMR signal of variable chemical shift
  which can be eliminated by exchange with
  deuterium from D2O.
• Hydrogen atoms on the carbon of a 1o or 2o
  alcohol produce a signal in the 1H NMR spectrum
  between d 3.3 and d 4.0 ppm that integrates for 2
  and 1 hydrogens, respectively.
• The 13C NMR spectrum of an alcohol shows a signal
  between d 50 and d 90 ppm for the alcohol carbon.

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1. Organometallic Compounds

• Compounds that contain carbon-metal bonds are
  called organometallic compounds.

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1. Preparation of Organolithium Organomagnesium
   Compounds

6A. Organolithium Compounds

• Preparation of organolithium compounds

• Order of reactivity of RX
• RI gt RBr gt 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 gt RBr gt RCl

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• Example

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1. Reactions of Organolithium andOrganomagnesium
   Compounds

7A. Reactions with Compounds Con-taining Acidic
Hydrogen Atoms

• 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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7B. Reactions of Grignard Reagentswith Epoxides
(Oxiranes)

• Grignard reagents react as nucleophiles with
  epoxides (oxiranes), providing convenient
  synthesis of alcohols.

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• Proceeds via an SN2 reaction

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• Also work for substituted epoxides
• (attacks the least substituted side).

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7C. Reactions of Grignard Reagentswith Carbonyl
Compounds
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• Mechanism

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1. Alcohols from Grignard Reagents

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• R, R H (formaldehyde)
• Yields a 1o alcohol.

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• R alkyl, R H (higher aldehydes)
• Yields a 2o alcohol.

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• R, R alkyl (ketone)
• Yields a 3o alcohol.

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• Reaction with esters
• Yields a 3o alcohol

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• Mechanism

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• Examples (note two separate steps)

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• Examples

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• Examples

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• Examples (reacts twice with an ester)

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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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8B. Restrictions on the Use ofGrignard 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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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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8D. The Use of Sodium Alkynides

• Preparation of sodium alkynides

• Reaction via ketones (or aldehydes).

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1. 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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? END OF CHAPTER 12 ?