Carbonyl groups and alcohols can be interconverted by oxidation and reduction reactions

(1)

Carbonyl groups and alcohols can be interconverted by

oxidation and reduction reactions

_{Alcohols can be oxidized to aldehydes; aldehydes can be reduced to alcohols}

(2)

_{Oxidation-Reduction Reactions in Organic}

Chemistry

_{Reduction: increasing the hydrogen content or decreasing the}

oxygen content of an organic molecule

_{A general symbol for reduction is [H]}

(3)

_{Oxidation-Reduction Reactions in Organic}

Chemistry

_{Oxidation: increasing the oxygen content or decreasing the}

hydrogen content of an organic molecule

_{A general symbol for oxidation is [O]}

_{Oxidation can also be defined as a reaction that increases the content of any}

element more electronegative than carbon

(4)

_{Alcohols by Reduction of Carbonyl Compounds}

_{A variety of carbonyl compounds can be reduced to alcohols}

Chapter 12

4 Use NaBH

₄

to reduce aldehydes and ketones

(5)

Why do you need a stronger reducing agent with esters and

carboxylic acids??

Consider the electrophilicity of the C atom in each of the

following carbonyl compounds? Rank their electrophilicity.

O

H

O

Chapter 12

5

(6)

_{Carboxylic acids and esters are considerably less reactive to}

reduction than aldehydes and ketones and require the use of LAH

Chapter 12

6 _{Lithium aluminium hydride is very reactive with water and must be}

used in an anhydrous solvent such as ether

_{Sodium borohydride is considerably less reactive and can be used in solvents}

(7)

_{Alcohols by Reduction of Carbonyl Compounds}

_{Carboxylic acids can be reduced to primary alcohols}

_{These are difficult reductions and require the use of powerful reducing agents}

such as lithium aluminum hydride (LiAlH₄also abbreviated LAH)

(8)

(9)

_{Esters are also reduced to primary alcohols}

_{LAH or high pressure hydrogenation can accomplish this transformation}

(10)

Aldehydes and ketones are reduced to 1

o

_{and 2}

o

_alcohols

respectively

_{Aldehydes and ketones are reduced relatively easily; the mild reducing agent}

sodium borohydride (NaBH₄) is typically used

_{LAH and hydrogenation with a metal catalyst can also be used}

(11)

_{Oxidation of Alcohols}

_{Oxidation of Primary Alcohols to Aldehydes}

_{A primary alcohol can be oxidized to an aldehyde or a carboxylic}

acid

_{The oxidation is difficult to stop at the aldehyde stage and usually proceeds to the}

carboxylic acid

(12)

_{Oxidation of Alcohols}

_{Oxidation of Primary Alcohols to Aldehydes}

_{A reagent which stops the oxidation at the aldehyde stage is}

pyridinium chlorochromate (PCC)

_{PCC is made from chromium trioxide under acidic conditions} _{It is used in organic solvents such as methylene chloride (CH}

2Cl2)

(13)

_{Oxidation of Primary Alcohols to Carboxylic Acids}

_{Potassium permanganate (KMnO}

₄

_{) is a typical reagent used for}

oxidation of a primary alcohol to a carboxylic acid

_{The reaction is generally carried out in aqueous solution; a brown precipitate of}

MnO₂indicates that oxidation has taken place

(14)

_{Oxidation of Secondary Alcohols to Ketones}

_{Oxidation of a secondary alcohol stops at the ketone}

_{Many oxidizing agents can be used, including chromic acid (H}

2CrO4) and Jones

reagent (CrO₃in acetone)

(15)

_{Organometallic Compounds}

_{Carbon-metal bonds vary widely in character from mostly covalent}

to mostly ionic depending on the metal

_{The greater the ionic character of the bond, the more reactive the}

Chapter 12

15 _{The greater the ionic character of the bond, the more reactive the}

compound

_{Organopotassium compounds react explosively with water and burst into flame}

when exposed to air

(16)

_{Preparation of Organolithium and}

Organo-magnesium Compounds

_{Organolithium Compounds}

_{Organolithium compounds can be prepared by reaction of an alkyl}

halide with lithium metal in an ether solvent

_{The order of reactivity of halides is R-I > R-Br > R-Cl (R-F is seldom used)}

Chapter 12

16

(17)

_{Grignard Reagents}

_{Grignard reagents are prepared by the reaction of organic halides}

with magnesium turnings

Where X = I, Br or Cl

(18)

_{Reactions of Organolithium and}

Organo-magnesium Compounds

_{Organolithium and Grignard reagents behave as if they were}

carbanions and they are therefore very strong bases

_{They react readily with hydrogen atoms attached to oxygen, nitrogen or sulfur, in}

addition to other acidic hydrogens (water and alcohol solvents cannot be used)

(19)

_{Organolithium and Grignard reagents can be used to form}

alkynides by acid-base reactions

_{Alkynylmagnesium halides and alkynyllithium reagents are useful nucleophiles}

for C-C bond synthesis

(20)

_{Reactions of Grignard Reagents with Oxiranes}

(Epoxides)

_{Grignard reagents are very powerful nucleophiles and can react}

with the

δ

_{+ carbons of oxiranes}

_{The reaction results in ring opening and formation of an alcohol product} _{Reaction occurs at the least-substituted ring carbon of the oxirane}

_{The net result is carbon-carbon bond formation two carbons away from the}

alcohol

(21)

(22)

_{Reaction of Grignard Reagents with Carbonyl}

Compounds

_{Nucleophilic attack of Grignard reagents at carbonyl carbons is}

the most important reaction of Grignard reagents

_{Reaction of Grignard reagents with aldehydes and ketones yields a new}

carbon-carbon bond and an alcohol

Chapter 12

22

(23)

For a Class 1 Carbonyl (ie. an aldehyde or ketone), the

nucleophilic addition mechanism operates.

(24)

(25)

_{Alcohols from Grignard Reagents}

_{Aldehydes and ketones react with Grignard reagents to yield}

different classes of alcohols depending on the starting carbonyl

compound

(26)

In the case of esters, nucleophilic acyl substitution starts us off…

Chapter 12

26

(27)

_{Esters react with two molar equivalents of a Grignard reagent to}

yield a tertiary alcohol

_{A ketone is formed by the first molar equivalent of Grignard reagent and this}

immediately reacts with a second equivalent to produce the alcohol

_{The final product contains two identical groups at the alcohol carbon that are both}

derived from the Grignard reagent

Chapter 12

27

(28)

(29)

_{The Use of Lithium Reagents}

_{Organolithium reagents react similarly to Grignard reagents}

_{Organolithium reagents tend to be more reactive}

_{The Use of Sodium Alkynides}

Chapter 12

29 _{Sodium alkynides react with carbonyl compounds such as}

(30)

What about carboxylic acids??

R

OH

O

+ R'-MgX

Chapter 12

30 While it is possible to do Grignard chemistry on carboxylic acids

using excess reagent (see the LiAlH

₄

reduction of a carboxylic

acid for an analogy), these reactions are generally avoided.

(31)

_{Restrictions on the Use of Grignard Reagents}

_{Grignard reagents are very powerful nucleophiles and bases}

_{They react as if they were carbanions}

_{Grignard reagents cannot be made from halides which contain}

acidic groups or electrophilic sites elsewhere in the molecule

(32)

_{Restrictions on the Use of Grignard Reagents}

_{The substrate for reaction with the Grignard reagent cannot}

contain any acidic hydrogen atoms

_{The acidic hydrogens will react first and will quench the Grignard reagent}

_{Two equivalents of Grignard reagent could be used, so that the first equivalent is}

consumed by the acid-base reaction while the second equivalent accomplishes carbon-carbon bond formation