Download Reaction with Hydrogen Halides

Section 16.6
REACTIONS OF ALCOHOLS: A
REVIEW AND A PREVIEW
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Reaction with Hydrogen Halides
• We have previously seen the reaction of ROH with
hydrogen halides HX to give alkyl halides
• Alcohols can be transformed into a variety of other
functional groups
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Functional Group Transformations
• SOCl2 and PBr3 also convert ROH to alkyl halides.
Oxygen acts as a nucleophile in these reactions
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Functional Group Transformations
• Oxygen also acts as a nucleophile in the conversion of
ROH to sulfonates
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Elimination
• Dehydration of alcohols using strong, non-nucleophilic
acid yields alkenes
• Rearrangements are sometimes observed; reactivity
trend is 3º > 2º > 1º
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Section 16.7
CONVERSION OF ALCOHOLS
TO ETHERS
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Synthesis of Ethers
• The oxygen in a protonated alcohol ROH2+ is electrophilic
• The oxygen of an alcohol ROH is nucleophilic
• When ROH is heated with an acid catalyst, nucleophilic O in
ROH attacks the electrophilic carbon, displacing water
• The product is a symmetric ether
• Only primary alcohols can be used; 2º and 3º alcohols undergo
elimination (dehydration)
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Synthesis of Ethers
• The oxygen in a protonated alcohol ROH2+ is electrophilic
• The oxygen of an alcohol ROH is nucleophilic
• When ROH is heated with an acid catalyst, nucleophilic O in
ROH attacks the electrophilic carbon, displacing water
• The product is a symmetric ether
• Diols can react intramolecularly to give cyclic ethers
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Section 16.8
ESTERIFICATION
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Fischer Esterification
• Under acidic conditions, alcohols and carboxylic acids form
esters reversibly
• Adding an excess of one reactant can drive the reaction forward
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Fischer Esterification
• Under acidic conditions, alcohols and carboxylic acids form
esters reversibly
• Removing a product (H2O) also drives the reaction forward
The mechanism will be discussed in a later chapter; for now,
note that the alcohol C–O bond remains intact.
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Acid Chlorides
• Acid chlorides are strongly electrophilic at the carbonyl carbon;
they react with nucleophilic alcohols (usually with some base) to
form esters
• Anhydrides can also be used
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Section 16.9
OXIDATION OF ALCOHOLS
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Oxidation of Alcohols
• Just as carbonyls can be reduced to alcohols, alcohols can be
oxidized to carbonyls
• Oxidation can be stopped at the aldehyde stage or carried
through to the carboxylic acid (depending on the oxidant used)
• Chromic acid (H2CrO4) is a strong oxidant used to form
carboxylic acids from primary alcohols
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Mild Oxidation to Form Aldehydes
• More mildly acidic chromate salts can be used to oxidize
primary alcohols to aldehydes
– Pyridinium chlorochromate (PCC)
– Pyridinium dichromate (PDC)
Secondary alcohols form ketones, but tertiary alcohols do not
react or form complicated mixtures of products.
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Mechanism of Chromate Oxidation
• The general mechanism of alcohol oxidation involves two stages:
– The alcohol hydrogen (–OH) is transformed into a good leaving
group (–OLG)
– b-Elimination across C–O eliminates H–LG and forms C=O
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Mechanism of Chromate Oxidation
• The general mechanism of alcohol oxidation involves two stages:
– The alcohol hydrogen (–OH) is transformed into a good leaving
group (–OLG)
– b-Elimination across C–O eliminates H–LG and forms C=O
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Other Oxidants: Swern Oxidation
• Other ROH oxidants are based on these same principles
• (CH3)2S + (COCl)2 forms the electrophilic (CH3)2SCl+ ion,
which promotes oxidation of ROH
• This reaction is called the Swern oxidation
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Section 16.10
BIOLOGICAL OXIDATION OF
ALCOHOLS
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Biological Oxidation of ROH
• Oxidation of alcohols and reduction of carbonyls are
important biological processes
• For example, ethanol is oxidized to acetaldehyde by the
enzyme alcohol dehydrogenase
• Chromium-based oxidants are far too strong for a
biological context!
The nicotinamide group is “nature’s oxidant.”
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Mechanism of NAD+ Oxidation
• The alcohols transfers hydride (C–H) to NAD+, forming
NADH
• Deprotonation of O–H by a basic group in the enzyme
occurs simultaneously
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