Title: Chap 9: Alcohols, Ethers
1Chap 9 Alcohols, Ethers Epoxides
IntroductionStructure and Bonding
- Alcohols contain a hydroxy group (OH) bonded to
an sp3 hybridized carbon.
2Alcohols, Ethers and Epoxides
IntroductionStructure and Bonding
- Compounds having a hydroxy group on a sp2
hybridized carbonenols and phenolsundergo
different reactions than alcohols.
- Ethers have two alkyl groups bonded to an oxygen
atom.
3Alcohols, Ethers and Epoxides
IntroductionStructure and Bonding
- Epoxides are ethers having the oxygen atom in a
three-membered ring. Epoxides are also called
oxiranes.
- The COC bond angle for an epoxide must be 60,
a considerable deviation from the tetrahedral
bond angle of 109.5. Thus, epoxides have angle
strain, making them more reactive than other
ethers.
4Alcohols, Ethers and Epoxides
Physical Properties
- Alcohols, ethers and epoxides exhibit
dipole-dipole interactions because they have a
bent structure with two polar bonds. - Alcohols are capable of intermolecular (and
intramolecular eg protiens DNA RNA) hydrogen
bonding. So, alcohols are more polar than ethers
and epoxides.
- Steric factors affect hydrogen bonding.
5Alcohols, Ethers and Epoxides
6Alcohols, Ethers and Epoxides
Preparation of Alcohols, Ethers, and Epoxides
- Alcohols and ethers are common products of
nucleophilic substitution.
- Williamson ether synthesis.
7Alcohols, Ethers and Epoxides
Preparation of Alcohols, Ethers, and Epoxides
- Unsymmetrical ethers can be synthesized in two
different ways usually one approach is preferred.
8Preparation of Alcohols, Ethers, and Epoxides
- An alkoxide salt is needed to make an ether.
- Alkoxides are prepared from alcohols by a
BrØnsted-Lowry acidbase reaction.
- NaH is an especially good base for this because
the by-product of the reaction, H2, is a gas that
just bubbles out of the reaction mixture.
9Preparation of Alcohols, Ethers, and Epoxides
- Organic compounds that contain both a hydroxy
group and a halogen atom on adjacent carbons are
called halohydrins. - In halohydrins, an intramolecular version of the
Williamson ether synthesis can occur to form
epoxides.
10Reactions of Alcohols
- The OH group in alcohols is a very poor leaving
group.
- For an alcohol to undergo nucleophilic
substitution, the OH must be converted into a
better leaving group. Example an acid can
convert the OH into H2O, giving a good leaving
group.
11Reactions of AlcoholsDehydration
- Dehydration, like dehydrohalogenation, is a ?
elimination reaction in which the elements of OH
and H are removed from the ? and ? carbon atoms
to form water.
- Dehydration is usually carried out using H2SO4
and other strong acids, or phosphorus oxychloride
(POCl3) in the presence of an amine base.
12Reactions of AlcoholsDehydration
- Common acids used for alcohol dehydration are
H2SO4 or p-toluenesulfonic acid (TsOH) tosyl.
- More substituted alcohols dehydrate more easily
13Reactions of AlcoholsDehydration
- When an alcohol has two or three ? carbons,
dehydration is regioselective and follows the
Zaitsev rule. - The more substituted alkene is the major product
when a mixture of constitutional isomers is
possible.
14Reactions of AlcoholsDehydration
- Secondary and 3 alcohols react by an E1
mechanism, whereas 1 alcohols react by an E2
mechanism.
Example as a review of E1 and E2 mechanisms
15Reactions of AlcoholsDehydration
- The E1 dehydration of 20 and 30 alcohols with
acid gives elimination products without
significant amounts of by-products from an SN1
reaction. - Elimination takes place because the reaction
mixture contains no good nucleophile to react
with the intermediate carbocation, so little/no
competing SN1 reaction. - So, E1 dehydration of alcohols is much more
synthetically useful than the E1
dehydrohalogenation of alkyl halides.
16Reactions of AlcoholsDehydration
- Since 1 carbocations are highly unstable, their
dehydration cannot occur by an E1 mechanism
involving a carbocation intermediate. Therefore,
1 alcohols undergo dehydration following an E2
mechanism.
Example as a review of E2 mechanism
17Alcohols, Ethers and Epoxides
Reactions of AlcoholsDehydration
- Entropy favors product formation in dehydration,
but enthalpy does not, since the ? bonds broken
in the reactant are stronger than the ? and ?
bonds formed in the products (broken formed).
So, distill away product as it is formed.
18Carbocation Rearrangementshydride shifts
- When carbocations are intermediates, a less
stable carbocation can sometimes be converted
into a more stable carbocation by a shift of a
hydrogen or an alkyl group (a rearrangement).
Example of a shift from a secondary alcohol to
tertiary carbocat
19Dehydration of Alcohols Using POCl3 and Pyridine
- Many organic compounds decompose when exposed to
a strong acid, so... phosphorus oxychloride
(POCl3) and pyridine (an amine base) can be used
in place of H2SO4 or TsOH.
- POCl3 converts a poor leaving group (OH) into a
good leaving group. - Dehydration then follows an E2 mechanism.
Mechanism
20Conversion of Alcohols to Alkyl Halides with HX
- Substitution reactions do not occur with alcohols
unless OH is converted into a good leaving group.
- The reaction of alcohols with HX (X Cl, Br, I)
is a good method to prepare 1, 2, and 3 alkyl
halides.
21Conversion of Alcohols to Alkyl Halides with HX
- This order of reactivity can be rationalized by
considering the reaction mechanisms involved. The
mechanism depends on the structure of the R group.
Mechanism
So primary give inversion, tertiary racemic mix
22Conversion of Alcohols to Alkyl Halides with HX
- The reactivity of hydrogen halides increases with
increasing acidity.
- Because Cl is a poorer nucleophile than Br or
I, the reaction of 10 alcohols with HCl occurs
only when an additional Lewis acid catalyst.
23Conversion of 1o nad 2o Alcohols to Alkyl Halides
with SOCl2 and PBr3
- SOCl2 (thionyl chloride) converts alcohols into
alkyl chlorides. - PBr3 (phosphorus tribromide) converts alcohols
into alkyl bromides. - Both reagents convert OH into a good leaving
group in situ (directly in the reaction mixture)
AND provide the nucleophile to displace the
leaving group!
Mechanism, similar for the two reagents
Pyridine is a common solvent that is converted
into pyridinium chloride, but its not
green. Need a nitrogen containing solvent
24(No Transcript)
25Alcohols Tosylates
- Tosylate is a good leaving group its conjugate
acid, p-toluenesulfonic acid (CH3C6H4SO3H, TsOH)
is a strong acid with pKa -7.
Tosyl formation though retention of
configuration, then mechanism can go either way
inversion or racemic
26Alcohols Tosylates
- Tosylate is a good leaving group, so both
nucleophilic substitution and ? elimination can
occur. - Best to treat with either a strong nucleophile or
bases, so get SN2 or E2.
- SN2 mechanism gives inversion of configuration
when chiral.
Mechanism compare methoxide with t-butoxide
nucleophiles on ROTs
27Summary alcohols
28Reaction of Ethers with Strong Acid not
synthetically very usefuldont focus on this
29Reactions of Epoxides
- Epoxides contain a strained three-membered ring
with two polar bonds. - Nucleophilic attack opens the strained
three-membered ring, making it a favorable
process even with a poor leaving group.
Mechanism to open, create chiral centers, then
convert OH to Lv grp if want
30Reactions of Epoxides which side do I attack?
31Reactions of Epoxides Stereochemistry of
opening (acid or base catalyzed)
Nucleophilic attack of OCH3 occurs from the
backside at either CO bond, because both ends
are similarly substituted.
32Reactions of Epoxides acid cat formation of 1,2
diols NOT enant pure though!
33Reactions of Epoxides
Balance with sterics too
34Reactions of Epoxides Ring opening acidic or
basic
- Ring opening of an epoxide with either a strong
nucleophile or an acid HZ is regioselective
because one constitutional isomer is the major or
exclusive product. - The site of selectivity of these two reactions is
opposite from another.