Download - Chapter 10 Reactions of Alcohols, Amines, Ethers, Epoxides, and Sulfur-Containing Compounds
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Chapter 10
Reactions of Alcohols,Amines, Ethers, Epoxides, and
Sulfur-Containing Compounds
Organic Chemistry 6th Edition
Paula Yurkanis Bruice
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Convert the strongly basic leaving group (OH–) into the good leaving group, H2O (a weaker base):
Only weakly basic nucleophiles can be used
Alcohols and ethers have to be activated before they can undergo a substitution or an elimination reaction:
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Primary, secondary, and tertiary alcohols all undergonucleophilic substitution reactions with HI, HBr, and HCl:
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Secondary and tertiary alcohols undergo SN1 reactions with hydrogen halides:
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Primary alcohols undergo SN2 reactions with hydrogen halides:
Reaction carried out in 48% aqueous HBr. Recall
that Br– is an excellent nucleophile in water.
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ZnCl2 can be used to catalyze certain SN2 reactions:
ZnCl2 functions as a Lewis acid that complexes strongly with the lone-pair electrons on oxygen:
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The Lucas ReagentAnhydrous ZnCl2 in conc HCl
Distinguishes primary, secondary, and tertiary low-molecular-weight alcohols
The Lucas reaction:
ROH + HClZnCl2
RCl
Positive test: Solution becomes cloudy
Test results and mechanisms at room temperature:• Primary: No reaction• Secondary: Reaction in ~5 minutes• Tertiary, allylic, and benzylic: Reaction immediate
SN2
SN1
SN2 and SN1
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Look out for rearrangement product in the SN1 reactionof the secondary or tertiary alcohol:
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Other Methods for Converting Alcohols into Alkyl Halides
Utilization of phosphorus tribromide:
Other phosphorus reagents can be used:PBr3, phosphorus tribromidePCl3, phosphorus trichloridePCl5, phosphorus pentachloridePOCl3, phosphorus oxychloride
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Activation by SOCl2
Pyridine is generally used as a solvent and also acts as a base:
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The Artificial Sweetener Splenda (Sucralose)
Could Splenda be a cellular alkylating agent?
No, it is too polar to enter a cell.
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Summary: Converting of Alcohols to Alkyl Halides
Recommended procedures:
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Converting Alcohols into Sulfonate Esters
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Several sulfonyl chlorides are available to activate OH groups:
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Dehydration of Secondary and Tertiary Alcohols by an E1 Pathway
To prevent the rehydration of the alkene product, one needs to remove the product as it is formed
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The major product is the most stable alkene product:
The most stable alkene product has the most stable transition state
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The rate of dehydration reflects the ease with which thecarbocation is formed:
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Look out for carbocation rearrangement:
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Complex Alcohol Rearrangements in Strong Acid
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Pinicol RearrangementProtonate alcohol: Eliminate water:
Rearrange carbocation: Deprotonate:
Resonance-stabilizedoxocarbocation
H3CO
CH3
H3C CH3
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Ring Expansion and Contraction
Show the mechanism for this reaction:•Protonate the alcohol.•Eliminate water.•Rearrange carbocation to afford the more stable cyclohexane ring.•Deprotonate.
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Primary Alcohols Undergo Dehydration by an E2 Pathway
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The Stereochemical Outcome of the E1 Dehydration
Alcohols and ethers undergo SN1/E1 reactions unless they would have to form a primary carbocation
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A Milder Way to Dehydrate an Alcohol
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Oxidation by Chromium (VI)
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Oxidation of AlcoholsOxidation by chromic acid:
Secondary alcohols are oxidized to ketones
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Primary alcohols are oxidized to aldehydes and eventually carboxylic acids:
Mechanism:
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The oxidation of aldehydes to acids requires the presence of water:
In the absence of water, the oxidation stops at the aldehyde:PCC, a methylene chloride–soluble reagent:
No water present
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A tertiary alcohol cannot be oxidized and is converted to a stable chromate ester instead:
Di-tert-Butyl ChromateNo hydrogen on this carbon
Cr
O
O
OO
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Amines do not undergo substitution reactions becauseNH2
– is a very strong base (a very poor leaving group):
Protonation of the amine moiety does not solve the problem:
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Nucleophilic Substitution Reactions of Ethers
Ethers, like alcohols, can be activated by protonation:
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Ether cleavage: an SN1 reaction:
Ether cleavage: an SN2 reaction:
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Reagents such as SOCl2 and PCl3 can activate alcohols but not ethers
Ethers are frequently used as solvents because only theyreact with hydrogen halides
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Nucleophilic Substitution Reactions of Epoxides
Recall Section 4.9
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Epoxides are more reactive than ethers in nucleophilicsubstitution reactions because of ring strain:
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Acid-Catalyzed Epoxide Ring OpeningHBr:
Aqueous acid:
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Acidic methanol:
Stereospecificity of epoxide ring opening:
A trans diol
Reason: Back-side attack of water on protonated epoxide:
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Reaction of an epoxide in the presence of methanol and acid
Mechanism:
Regioselectivity:
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When a nucleophile attacks an unprotonated epoxide,the reaction is a pure SN2 reaction:
Therefore:
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Epoxides Are Synthetically Useful Reagents
Enantiomers
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Epoxy resins are the strongest adhesives known:
Amine nucleophile mediated epoxide ring opening:
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Arene Oxides
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Arene oxide fate:
Enantiomers
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Mechanism for arene oxide rearrangement:
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Arene oxides as a carcinogen:
DNAbackbone
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BENZO[a]PYRENE EPOXIDATION
Not all smokersget cancer
Benzopyrenes in chimneys were responsible for cancer of the scrotum in “chimney-boys.” The connection between cancer and chimney soot was made by Percivall Pott in 1775.
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Crown Ethers
The ability of a host to bond only certain guests is an example of molecular recognition
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Thiols are sulfur analogs of alcohols:
Thiols are not good at hydrogen bonding
Thiols form strong complexes with heavy metal cations
Thiols are stronger acids (pKa = 10) than alcohols
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In protic solvent, thiolate ions are better nucleophiles than alkoxide ions:
Sulfur is an excellent nucleophile because its electroncloud is polarized