KO II. Reaksi alkohol.amina .eter

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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 undergo

nucleophilic substitution reactions with HI, HBr, and HCl:

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Primary alcohols undergo S_N2 reactions with hydrogen halides:

Reaction carried out in 48% aqueous HBr. Recall that Br– is an excellent nucleophile in water.

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ZnCl₂can be used to catalyze certain S_N2 reactions:

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The Lucas Reagent

Anhydrous ZnCl₂ in conc HCl

Distinguishes primary, secondary, and tertiary low-molecular-weight alcohols

The Lucas reaction:

ROH + HCl

ZnCl2

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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Other Methods for Converting Alcohols

into Alkyl Halides

Utilization of phosphorus tribromide:

Other phosphorus reagents can be used:

PBr3, phosphorus tribromide

PCl3, phosphorus trichloride

PCl₅, phosphorus pentachloride POCl3, phosphorus oxychloride

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Activation by SOCl

₂

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The Artificial Sweetener

Splenda (Sucralose)

Could Splenda be a cellular alkylating agent?

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Summary: Converting of

Alcohols to Alkyl Halides

Recommended procedures:

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Several sulfonyl chlorides are available to activate OH groups:

Dehydration of Secondary and Tertiary

Alcohols by an E1 Pathway

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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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Look out for carbocation rearrangement:

Complex Alcohol

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Pinicol Rearrangement

Protonate alcohol: Eliminate water:

Rearrange carbocation: Deprotonate:

Resonance-stabilized

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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.

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Primary Alcohols Undergo Dehydration

by an E2 Pathway

The Stereochemical Outcome of

the E1 Dehydration

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A Milder Way to Dehydrate an Alcohol

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Oxidation of Alcohols

Oxidation by chromic acid:

Secondary alcohols are oxidized to ketones

Primary alcohols are oxidized to aldehydes and eventually carboxylic acids:

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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 Chromate} No hydrogen on

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Amines do not undergo substitution reactions because NH₂– _{is a very strong base (a very poor leaving group):}

Protonation of the amine moiety does not solve the problem:

Nucleophilic Substitution

Reactions of Ethers

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Ether cleavage: an S_N1 reaction:

Ether cleavage: an S_N2 reaction:

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Reagents such as SOCl₂and PCl₃ can activate alcohols but not ethers

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Nucleophilic Substitution

Reactions of Epoxides

Recall Section 4.9

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Acid-Catalyzed Epoxide Ring Opening

HBr:

Aqueous acid:

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Stereospecificity of epoxide ring opening:

A trans diol

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Reaction of an epoxide in the presence of methanol and acid

Mechanism: Regioselectivity:

When a nucleophile attacks an unprotonated epoxide, the reaction is a pure S_N2 reaction:

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Epoxides Are Synthetically

Useful Reagents

Enantiomers

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Epoxy resins are the strongest adhesives known:

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Arene Oxides

Arene oxide fate:

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Mechanism for arene oxide rearrangement:

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Arene oxides as a carcinogen:

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BENZO[a]PYRENE EPOXIDATION

Not all smokers get 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.

Crown Ethers

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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 (p_Ka = 10) than alcohols

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In protic solvent, thiolate ions are better nucleophiles than alkoxide ions: