Transcript unit 6 alcohols

Unit 6
Alcohols and Ethers
Alcohols




Nomenclature
Physical Properties
Synthesis
Reactions
Alcohols
 contain at least one C-OH bond.
 are similar in structure to water
(an alkyl group replaces one of the
H’s in water).
 The C bonded to the -OH is called
the carbinol C atom.
Nomenclature of Alcohols
methyl
alcohol
2° alcohol
phenol
1° alcohol
3° alcohol
Nomenclature of Alcohols
 Apply the same rules you learned for
the alkanes.
 Use the root name of the longest chain
containing the hydroxyl group, but
change -e to -ol.
IUPAC:
methanol
common:
methyl alcohol
IUPAC:
butan-1-ol
1-butanol
common:
n-butyl alcohol
Nomenclature of Alcohols
 Number the longest C chain
containing the -OH, starting at
the end nearer the -OH, and use
the appropriate number to
indicate the position of the -OH.
Br
OH
IUPAC:
6-bromoheptan-3-ol
6-bromo-3-heptanol
Nomenclature of Alcohols
 With a cyclic alcohol, the -OH is
assumed to be on the #1 C.
CH3
IUPAC:
2-methylcyclohexanol
OH
Nomenclature of Alcohols
 Priority: The alcohol is the highest
priority functional group of the ones
we have studied so far:






Alcohols
Amines
Alkenes/Alkynes
Alkanes
Ethers
Halides
Nomenclature of Alcohols
OH
IUPAC:
(E)-hept-5-en-3-ol
trans-5-hepten-3-ol
OH
IUPAC:
cyclohex-2-en-1-ol
Nomenclature of Alcohols
 An alcohol group that is a
substituent is called “hydroxy”.
O
OH
OH
IUPAC:
2-hydroxybutanoic acid
Nomenclature of Alcohols
 Alcohols with two -OH groups are
diols.
 Vicinal diols are called glycols.
IUPAC:
propane-1,2-diol
common:
propylene glycol
OH
OH
IUPAC:
4-cyclopentylheptane-3,5-diol. Note the “e.”
Nomenclature of Thiols
 A thiol is an organic compound
with an -SH group, the sulfur
analog of an alcohol.
 aka a mercaptan
IUPAC:
4-cyclopentylheptane-3-thiol
SH
Nomenclature of Phenols
IUPAC:
2-bromophenol
common:
ortho-bromophenol
IUPAC:
3-bromophenol
common:
meta-bromophenol
IUPAC:
4-bromophenol
common:
para-bromophenol
Nomenclature of Phenols
IUPAC:
benzene-1,4-diol
common:
hydroquinone
IUPAC:
benzene-1,3-diol
common:
resorcinol
IUPAC:
benzene-1,2-diol
common:
catechol
Nomenclature of Alcohols
 Give IUPAC acceptable names.
OH
3-(iodomethyl)-2-isopropylpentan-1-ol
HO
CH2I
OH
Cl
CH2CH2OH
(1R,3S)-3-(2-hydroxyethyl)cyclopentanol
(Z)-4-chlorobut-3-en-2-ol
IR spectrum of alcohol with
hydrogen bonding
Cyclohexanol, neat
SDBSWeb : http://riodb01.ibase.aist.go.jp/sdbs/ (National Institute
of Advanced Industrial Science and Technology, 10/16/11)
IR spectrum of alcohol with
very little hydrogen bonding
Cyclohexanol in CCl4
SDBSWeb : http://riodb01.ibase.aist.go.jp/sdbs/ (National Institute
of Advanced Industrial Science and Technology, 9/3/11)
Physical Properties of Alcohols
 The -OH group is polar and forms
a hydrogen bond.
 The boiling points of alcohols are
high: Most of the common alcohols
up to C11 or C12 are liquids at room
temperature.
 The short-chain alcohols are
miscible with water.
Physical Properties of Alcohols
 BP increases with the amount of
H-bonding.
 1-propanol
 1,2-propanediol
bp = 97°C
bp = 188°C
 propylene glycol
 1,2,3-propanetriol bp = 290°
 glycerol
Physical Properties of Alcohols
 The alkyl part of the alcohol is
nonpolar.
 As the carbon chain gets longer,
alcohols become more suitable for
dissolving nonpolar compounds.
 As the carbon chain gets longer,
alcohols become less soluble in
water.
 Rule of thumb: One -OH can carry 4
carbon atoms into solution.
Physical Properties of Alcohols
 Like water, the -OH group in an
alcohol can act as an acid and
lose H+.
Higher Ka, more acidic.
Lower pKa, more acidic.
Physical Properties of Alcohols
pKa
cyclohexanol
18.0
water
15.7
methanol
15.5
phenol
10.0
acetic acid
4.8
Physical Properties of Alcohols
 As the previous slide shows, alcohols are weak
acids.
 Only phenols react with NaOH to lose the H+.
 Other alcohols require a much stronger base
before they lose their acid H+.
Physical Properties of Alcohols
 Acidity increases with the ability to pull
electrons away from C-O-.
 e- withdrawing groups stabilize anions (edonating groups stabilize carbocations)
pKa=14.3
pKa=12.2
pKa=15.9
pKa=10.0
Physical Properties of Alcohols
 Phenols are the most acidic
alcohols because resonance
stabilizes the conjugate bases.
 …can you draw the resonancestabilized forms of the phenoxide
ion?
Synthesis of Alcohols - Review
 from SN2 of -OH with alkyl halides
 from alkenes




acid-catalyzed hydration
oxymercuration-demercuration
hydroboration-oxidation
hydroxylation (1,2-diols)
 from addition of acetylides to
carbonyl compounds
Synthesis of Alcohols - New
 industrial preparation of methanol
and ethanol
 from addition of organometallic
reagents to carbonyl compounds
 from reduction of carbonyl
compounds
Synthesis of Alcohols - Review
 from SN2 of -OH with alkyl halides (e.g.,
NaOH in acetone)


inversion of configuration
Synthesis of Alcohols - Review
 from alkenes
 acid-catalyzed hydration
Markovnikov
product
Synthesis of Alcohols - Review
 from alkenes
 oxymercuration-demercuration
Markovnikov product
anti addition
Synthesis of Alcohols - Review
 from alkenes
 hydroboration-oxidation
syn addition
Synthesis of Alcohols - Review
 from alkenes - syn hydroxylation to
make vicinal diols
 cold, dilute KMnO4 in base or OsO4/H2O2
Synthesis of Alcohols - Review
 from alkenes - anti hydroxylation to
make vicinal diols
 step 1: make the epoxide
 CH3CO3H (goes straight to diol if water is
present)
 MCPBA
 step 2: acidify
Synthesis of Alcohols - Review
 from addition of acetylides to
carbonyl compounds
Industrial Synthesis of Methanol
 widely used solvent and fuel
 Prepared from synthesis gas
Δ
 3C(coal) + 4H2O  CO2 + 2CO + 4H2
 Preparation requires a temperature of
300-400°C, H2 pressure of 200-300 atm,
and a CuO-ZnO/Al2O3 catalyst:
 CO(g) + 2H2 (g) CH3OH
Industrial Synthesis of Ethanol
 Solvent and fuel - The pure form is
subject to expensive taxes.
 Denatured alcohol contains impurities
that render it undrinkable.
 Prepared from ethylene:
 H2C=CH2(g) + H2O  CH3CH2OH
 Preparation requires a temperature of
300°C, an H2O pressure of 100-300 atm,
and a catalyst (phosphoric acid
adsorbed onto diatomaceous earth).
Synthesis of Alcohols - New
 from addition of organometallic
reagents to carbonyl compounds
or epoxides





formaldehyde
aldehydes
ketones
esters and acid chlorides
epoxides
 In every case, the C chain is
lengthened.
Organometallic Compounds
 contain a covalent bond between C
and a metal atom.
 Grignard reagents (R-MgX)
 organolithium reagents (R-Li)
 contain a nucleophilic C.
 Grignard reagents act like R:- +MgX
 organolithium reagents act like R:-Li+
Organometallic Compounds
 contain a nucleophilic C.
 We’ve already encountered a
nucleophilic C…in the acetylides.
 Sodium amide can deprotonate a
terminal alkyne, but not an alkene or
an alkane.
 To make an alkane or an alkene act as a
nucleophile, convert it into an
organometallic compound.
Organometallic Compounds
 Grignard reagents are made from an
alkyl halide and Mg in ether.
 Ether is needed to dissolve the Grignard
reagent.
CH3I + Mg
diethyl ether
CH3MgI
methylmagnesium iodide
Careful: Water destroys the Grignard reagent!
Organometallic Compounds
 Organolithium reagents are made from
an alkyl halide and Li in an ether or an
alkane.
CH3CH2Br + 2Li
ether or
alkane
CH3CH2Li + LiBr
ethyllithium
Careful: Water destroys the organolithium reagent!
Organometallic Compounds
CH3CH2Li + H2O
CH3CH3 + LiOH
ethyllithium
Careful: Water destroys the organolithium reagent!
Synthesis of Alcohols - New
 from addition of organometallic
reagents to formaldehyde
Step 1:
Why can’t step 2 be combined with step 1?
Step 2:
Synthesis of Alcohols - New
 from addition of organometallic
reagents to aldehydes
Synthesis of Alcohols - New
 from addition of organometallic
reagents to ketones
Synthesis of Alcohols - New
 from addition of organometallic reagents to
esters and acid chlorides to make 3°
alcohols with two identical groups.
 Two (2) moles of the reagent are needed.
Synthesis of Alcohols - New
 Two (2) moles of the reagent are needed.
Why?
 Acid chlorides: Cl- is a good LG, and so,
with one mole of the Grignard, a ketone
forms. The ketone can be attacked by a
second mole of the Grignard reagent.
 Esters: Now the LG is RO-, not usually
considered “good,” but the reaction takes
place by nucleophilic acyl substitution, not
by SN2. In this mechanism, RO- leaving is
exothermic and therefore favorable.
Synthesis of Alcohols - New
 from addition of organometallic
reagents to epoxides
 Grignard reagents will NOT react with
ethers, which is why ether is the solvent.
 The reagent attacks the less hindered (less
substituted) C of the epoxide.
Side Reactions of
Organometallic Reagents
 Grignard reagents and organolithium
compounds are strong bases and strong
nucleophiles.
 They react immediately and irreversibly
with water… and any other compound
that can protonate a strong base.
 O-H, N-H, S-H, -C≡C-H
 Grignard reagents cannot contain the
following unprotected groups, as they
will be attacked:
 C=O, C=N, C≡N, N=O.
Side Reactions of
Organometallic Reagents
 Water is a poison to these reagents:
CH3CH2MgBr + H-O-H  CH3CH3(g) + BrMgOH
 HOCH2CH2CH2CH2Br + 2Li do NOT
produce HOCH2CH2CH2CH2Li. The H
from the –OH reacts immediately:
HOCH2CH2CH2CH2Br + 2Li 
Li+ -OCH2CH2CH2CH3 + LiBr
Side Reactions of
Organometallic Reagents
 BrCH2CH2CH2CHO + Mg does not make a
usable Grignard reagent because
would react with the C=O of a second
molecule of the starting compound.
Side Reactions of
Organometallic Reagents
 Grignard reagents can couple with the
alkyl halide. Although this does not
happen to a great extent, it is an
unwanted side reaction that limits the
yield of the Grignard reagent.
CH3CH2CH2Br
+
Mg
ether
CH3CH2CH2MgBr + CH3CH2CH2Br
CH3CH2CH2MgBr
ether
CH3CH2CH2CH2CH2CH3
Coupling of Alkyl Groups Using
a Gilman Reagent
 Lithium dialkylcuprates (aka Gilman
reagents) are used when a coupling
with an alkyl halide (or vinyl halide or
aryl halide) is desired.
Gilman reagent
Synthesis of Alcohols - New
 from reduction of carbonyl
compounds
 NaBH4 reduces aldehydes and
ketones but not acids and esters.
 Alcohol, ether, or water is the solvent.
 LiAlH4 followed by H+ reduces any
C=O, including acids and esters.
 Raney nickel saturated with H2(g)
reduces C=O but also C=C.
 finely divided Ni “honeycomb” with
large surface area: fixed bed or slurry
NaBH4 and LiAlH4
 NaBH4 and LiAlH4 act as Hnucleophiles.
 In actuality, they deliver H- while
limiting its basicity.
 LiAlH4 (aka LAH) reacts explosively with
water and alcohols.
 LiAlH4 + 4H2O  LiOH + 4H2 + Al(OH)3
 NaBH4 reacts slowly with water and
alcohols if the pH is kept high.
 NaBH4 + 4H2O  NaOH + 4H2 + B(OH)3
Mechanism of Hydride
Reduction of Carbonyls
Mechanism of Hydride
Reduction of Carbonyls
H2O may be included with the NaBH4.
LAH Reduction of Carbonyls
 When using LiAlH4, H2O may not be
included with it but must be added
afterward (in a second reaction
step).
 Because Al is less electronegative
than B, LiAlH4 is a stronger
nucleophile and will react with less
reactive carbonyls such as esters, as
well as with the more active
aldehydes and ketones.
 LiAlH4 followed by H+ will separate an
ester into two alcohols.
Reduction of Carbonyls
Thiols (Mercaptans)
 -SH instead of -OH
 Thiols are more acidic than alcohols
 characteristic, unpleasant odor
 oxidize to give sulfonic acids
pKa = 7.8
Predict the Product
Cl
1. Mg(s)/ether
2. CH3CO2CH3
3. H3O+
Cl
1. Mg(s)/ether
2. CH3CH2CO2H
3. H3O+
Conversion
?
OH
D
Predict the Product
O
NaBH4
CH3CH2OH
O
O
1. LAH
2. H3O+
Predict the Product
HO
1. NaH/THF
2. CH3I
1. BH3.THF
2. H O /OH2 2