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Chapter 11
Alcohols & Ethers
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1. Structure & Nomenclature
Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp3 hybridized) 1o 2o 3o
Ethanol
2-Propanol
(isopropyl
alcohol)
2-Methyl-
2-propanol
(tert-butyl alcohol)
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Phenols
Compounds that have a hydroxyl group attached directly to a benzene ring
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Ethers
The oxygen atom of an ether is bonded to two carbon atoms
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6. 1A. Nomenclature of Alcohols
Rules of naming alcohols
Identify the longest carbon chain that includes the carbon to which the –OH group is attached
Use the lowest number for the carbon to which the –OH group is attached
Alcohol as parent (suffix)
ending with “ol”
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Examples
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Example
3-Propyl-2-heptanol
wrong or
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9. 1B. Nomenclature of Ethers
Rules of naming ethers
Similar to those with alkyl halides
CH3O– Methoxy
CH3CH2O– Ethoxy
Example
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Cyclic ethers
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2. Physical Properties of Alcohols and Ethers
Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW)
Alcohols have much higher boiling points than comparable ethers or hydrocarbons
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For example
Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot
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Water solubility of ethers and alcohols
Both ethers and alcohols are able to form hydrogen bonds with water
Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons
The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long-chain alcohols are more “alkane-like” and are, therefore, less like water
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Physical Properties of Ethers
Name
Formula mp
(oC)
bp (oC)
(1 atm)
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Physical Properties of Alcohols
Name
Formula mp
(oC)
bp (oC)
(1 atm) *
* Water solubility (g/100 mL H2O)
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3. Important Alcohols & Ethers
3A. Methanol
Methanol is highly toxic
Ingestion of even small quantities of methanol can cause blindness
Large quantities cause death
Methanol poisoning can also occur by inhalation of the vapors or by prolonged exposure to the skin
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3B. Ethanol
Ethanol can be produced by
Fermentation
Acid-catalyzed hydration of ethene
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18. 3C. Ethylene and Propylene Glycols
a good automobile
anti-freeze
as a low-toxicity, environmentally friendly alternative
to ethylene glycol
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3D. Diethyl Ether
Diethyl ether is a very low boiling, highly flammable liquid
Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides
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20. Step 1 Step 2 Hydrogen abstraction adjacent to the ether oxygen
occurs readily
Step 2
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21. Step 3a or Step 3b A hydroperoxide Hydroperoxides and peroxides
can be explosive
A peroxide
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4. Synthesis of Alcohols from Alkenes
Acid-catalyzed Hydration of Alkenes H⊕
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Acid-Catalyzed Hydration of Alkenes
Markovnikov regioselectivity
Free carbocation intermediate
Rearrangement of carbocation possible
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Oxymercuration–Demercuration
Markovnikov regioselectivity
Anti stereoselectivity
Generally takes place without the complication of rearrangements
Mechanism
Discussed in Section 8.5
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Hydroboration–Oxidation
Anti-Markovnikov regioselectivity
Syn-stereoselectivity
Mechanism
Discussed in Section 8.7
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26. Markovnikov regioselectivity
H+, H2O or
1. Hg(OAc)2, H2O, THF
2. NaBH4, NaOH
1. BH3 • THF
2. H2O2, NaOH
Anti-Markovnikov regioselectivity
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Example
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Synthesis (1)
Need anti-Markovnikov addition of H–OH
Use hydroboration-oxidation
1. BH3 • THF
2. H2O2, NaOH
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Synthesis (2)
Need Markovnikov addition of H–OH
Thus, could potentially use either
acid-catalyzed hydration or
oxymercuration-demercuration
However, acid-catalyzed hydration is NOT reasonable here due to likely rearrangement of carbocation
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Acid-catalyzed hydration H⊕
Rearrangement
of carbocation
(2o cation)
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Oxymercuration-demercuration
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5. Reactions of Alcohols
The reactions of alcohols have mainly to do with the following:
The oxygen atom of the –OH group is nucleophilic and weakly basic
The hydrogen atom of the –OH group is weakly acidic
The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions
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C–O & O–H bonds of an
alcohol are polarized
Protonation of the alcohol converts a poor leaving group (HO⊖) into a good one (H2O)
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Once the alcohol is protonated substitution reactions become possible
The protonated –OH
group is a good leaving
group (H2O)
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6. Alcohols as Acids
Alcohols have acidities similar to that of water
pKa Values for Some Weak Acids
Acid
pKa
CH3OH
15.5
H2O
15.74
CH3CH2OH
15.9
(CH3)3COH
18.0
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Relative Acidity
H2O & alcohols are the
strongest acids in this series
Increasing acidity
Relative Basicity
HO⊖ is the weakest
acid in this series
Increasing basicity
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7. Conversion of Alcohols into Alkyl Halides
HX (X = Cl, Br, I)
PBr3
SOCl2
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Examples
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8. Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides
The order of reactivity of alcohols 3o
The order of reactivity of the hydrogen halides
HI > HBr > HCl
(HF is generally unreactive)
> 2o
> 1o
< methyl
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HO⊖ is a poor
leaving group
H3O⊕ is a good
leaving group
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41. 8A. Mechanisms of the Reactions of Alcohols with HX
Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation
Step 1
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Step 2
Step 3
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Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN2 mechanism
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9. Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2
Reaction of alcohols with PBr3
The reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C)
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Reaction of alcohols with PBr3
Phosphorus tribromide is often preferred as a reagent for the transformation of an alcohol to the corresponding alkyl bromide
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Mechanism
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Reaction of alcohols with SOCl2
SOCl2 converts 1o and 2o alcohols to alkyl chlorides
As with PBr3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C)
Pyridine (C5H5N) is often included to promote the reaction
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Mechanism
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Mechanism
Cl⊖
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10. Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols
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Direct displacement of the –OH group with a nucleophile via an SN2 reaction is not possible since HO⊖ is a very poor leaving group
Thus we need to convert the HO⊖ to a better leaving group first
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Mesylates (OMs) and Tosylates (OTs) are good leaving groups and they can be prepared easily from an alcohol
(methanesulfonyl chloride)
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Preparation of Tosylates (OTs) from an alcohol
(p-toluenesulfonyl chloride)
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SN2 displacement of the mesylate or tosylate with a nucleophile is possible
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Example
Retention of
configuration
Inversion of
configuration
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Example
Retention of
configuration
Inversion of
configuration
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11. Synthesis of Ethers
11A. Ethers by Intermolecular Dehydration of Alcohols
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Mechanism
This method is only good for the synthesis of symmetrical ethers
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For unsymmetrical ethers
1o alcohols
Mixture
of ethers
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Exception
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11B. The Williamson Ether Synthesis
Via SN2 reaction, thus R is limited to 1o and some 2o (but R' can be 1o, 2o or 3o)
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Example 1
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Example 2
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Example 3
However
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11C. Synthesis of Ethers by Alkoxy- mercuration–Demercuration
Markovnikov regioselectivity
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Example
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11D. tert-Butyl Ethers by Alkylation of Alcohols: Protecting Groups
A tert-butyl ether can be used to “protect” the hydroxyl group of a 1o alcohol while another reaction is carried out on some other part of the molecule
A tert-butyl protecting group can be removed easily by treating the ether with dilute aqueous acid
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Example
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Direct reaction will not work
(Not Formed) ☓
Reason: Grignard reagents are basic and alcohols contain an acidic proton
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Need to “protect” the –OH group first
tert-butyl protected alcohol
deprotection
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Example
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Direct reaction will not work
(Not Formed) ☓
Instead
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12. Reactions of Ethers
Dialkyl ethers react with very few reagents other than acids
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12A. Cleavage of Ethers
Heating dialkyl ethers with very strong acids (HI, HBr, and H2SO4) causes them to undergo reactions in which the carbon–oxygen bond breaks
Cleavage of an ether
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Mechanism
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13. Epoxides
Epoxide (oxirane)
A 3-membered ring containing an oxygen
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13A. Synthesis of Epoxides: Epoxidation
Electrophilic epoxidation
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Peroxy acids (peracids)
Common peracids
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13B. Stereochemistry of Epoxidation
Addition of peroxy acid across a C=C bond
A stereospecific syn (cis) addition
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More electron-rich double reacts faster
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14. Reactions of Epoxides
The highly strained three-membered ring of epoxides makes them much more reactive toward nucleophilic substitution than other ethers
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Acid-catalyzed ring opening of epoxide
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Base-catalyzed ring opening of epoxide
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If the epoxide is unsymmetrical, in the base-catalyzed ring opening, attack by the alkoxide ion occurs primarily at the less substituted carbon atom
1o carbon atom is
less hindered
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In the acid-catalyzed ring opening of an unsymmetrical epoxide the nucleophile attacks primarily at the more substituted carbon atom
This carbon resembles a 3o carbocation
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15. Anti 1,2-Dihydroxylation of Alkenes via Epoxides
Synthesis of 1,2-diols
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Anti-Dihydroxylation
A 2-step procedure via ring-opening of epoxides
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16. Crown Ethers
Crown ethers are cyclic compounds containing many oxygen atoms
They are able to transport (i.e. dissolve) ionic compounds in organic solvents – phase transfer agent
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Crown ether nomenclature: x-crown-y
x = # of atoms in ring
y = # of oxygen atoms in ring
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Different crown ethers accommodate different guests in this guest-host relationship
18-crown-6 for K+
15-crown-5 for Na+
12-crown-4 for Li+
1987 Nobel Prize to Charles Pedersen (DuPont), D.J. Cram (UCLA) and J.M. Lehn (Strasbourg) for their research on ion transport, crown ethers
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Many important implications to biochemistry and ion transport
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17. Summary of Reactions of Alkenes, Alcohols, and Ethers
Synthesis of alcohols
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Synthesis of alcohols
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Synthesis of alcohols
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Reaction of alcohols
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Synthesis of ethers
Cleavage reaction of ethers
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