Alcohols and Phenols

17.6 Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents

Alcohols and Phenols

„ Alkyl, aryl, and vinylic halides react with

magnesium in ether or tetrahydrofuran to generate Grignard reagents, RMgX „ Grignard reagents react with carbonyl

Chapter 17 Part 2

compounds to yield alcohols

Mechanism of the Addition of a Grignard Reagent „ Grignard reagents act as nucleophilic carbon anions

(carbanions, : R−) in adding to a carbonyl group „ The intermediate alkoxide is then protonated to

produce the alcohol

Examples of Reactions of Grignard Reagents with Carbonyl Compounds

Examples of Reactions of Grignard Reagents with Carbonyl Compounds „ Formaldehyde reacts with Grignard reagents

to yield primary alcohols. „ Aldehydes react with Grignard reagents to

yield secondary alcohols. „ Ketones yield tertiary alcohols.

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Reactions of Esters and Grignard Reagents

Grignard Reagents and Other Functional Groups in the Same Molecule

„ Yields tertiary alcohols in which two of the

„ Can't be prepared if there are reactive functional

substituents carbon come from the Grignard reagent „ Grignard reagents do not add to carboxylic acids – they undergo an acid-base reaction, generating the hydrocarbon of the Grignard reagent

groups in the same molecule, including proton donors

Show the products obtained from addition of methylmagnesium bromide to the following:

How could you use a Grignard reaction to prepare the following alcohols?

„ Cyclopentanone

„2 -

Methyl- 2 - propanol

„1 -

Methylcyclohexanol

„3 -

Methyl- 3 - pentanol

„ Benzophenone (diphenyl ketone)

„ 3- Hexanone

„ Benzyl alcohol

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Synthesis of Diols Catalytic hydrogenation: O

O

HCCH2CHCH2CH CH3

H2

OH o

Ni, 125 C

3-Methylpentanedial

OH CH2CH2CHCH2CH2 CH3

3-Methyl-1,5-pentanediol

Synthesis of Diols Vicinal diols: diols with hydroxyl groups on adjacent carbons: OH HOCH2CH2OH 1,2-Ethanediol (ethylene glycol)

R2C CR2 + OsO4 Alkene

H H Cyclohexene

CH3CHCH2OH 1,2-Propanediol (propylene glycol)

1. OsO4, H2O2 2. OH -

R2C CR2 O

Osmium tetroxide

O

Os

O O

Cyclic osmate ester

17.7 Some Reactions of Alcohols

Dehydration of Alcohols to Yield Alkenes

„ Two general classes of reaction

„ The general reaction: forming an alkene from an

„ „

At the carbon of the C–O bond At the proton of the O–H bond

alcohol through loss of O-H and H (hence dehydration) of the neighboring C–H to give π bond „ Specific reagents are needed

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Acid- Catalyzed Dehydration „ Tertiary alcohols are readily dehydrated with acid „ Secondary alcohols require severe conditions (75%

H2SO4, 100°C) - sensitive molecules don't survive „ Primary alcohols require very harsh conditions –

impractical „ Reactivity is the result of the nature of the

carbocation intermediate (See Figure 17-5) „ Note that Zaitsev’s rule is followed!

Diagram the reaction mechanism for the dehydration of 2-methyl-2-butanol

Dehydration with POCl3 „ Phosphorus oxychloride in the amine solvent pyridine

can lead to dehydration of secondary and tertiary alcohols at low temperatures „ An E2 via an intermediate ester of POCl2 (see Figure 17.6)

Follows an E2 mechanism

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OH CH3CH2CHCH(CH3)2

POCl3 Pyridine, 0oC

?

Conversion of Alcohols into Alkyl Halides „ 3° alcohols are converted by HCl or HBr at low

temperature (Figure 17.7)

„ 1° and alcohols are resistant to acid – use SOCl2 or

PBr3 by an SN2 mechanism

Conversion of Alcohols into Tosylates „ Reaction with p- toluenesulfonyl chloride (tosyl

chloride, p - TosCl) in pyridine yields alkyl tosylates, ROTos „ Formation of the tosylate does not involve the C–O bond so configuration at a chirality center is maintained „ Alkyl tosylates react like alkyl halides

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Stereochemical Uses of Tosylates „ The SN2 reaction of an alcohol via a tosylate,

produces inversion at the chirality center

„ The SN2 reaction of an alcohol via an alkyl

halide proceeds with two inversions, giving product with same arrangement as starting alcohol

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