Alcohols
Alcohols
Alcohols
H O H R O H
H H R
R OH R OH R OH OH
H R R
primary secondary tertiary phenol
Alcohols with the hydroxyl bound directly to an aromatic (benzene) ring are
called phenols.
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Nomenclature of Alcohols
(Normally any compound’s name which ends in –ol is an alcohol of some
sort)
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(4) Cyclic alcohols have the prefix cyclo-, and the hydroxyl group is deemed
to be on C-1.
HO CH2CH3
1-ethylcyclopropanol
(5) Alcohols with double or triple bonds are named using the –ol suffix on
the alkene or alkyne name. Numbering gives the hydroxyl group the
lowest possible number. When numbers are also given for the multiple
bond position, the position of the hydroxyl can be written immediately
before the –ol prefix.
OH
H3C Cl
H H
(Z)-4-chloro-3-buten-2-ol
(6) If the hydroxyl group is only a minor part of the structure, it may be
named as a hydroxy- substituent.
OH
CO2H
3-hydroxybutanoic acid
They are named as for alcohols except the suffix –diol is used and two
numbers are required to locate the –OH’s.
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OH OH
1-cyclohexyl-1,3-butanediol
Nomenclature of Phenols
A phenol always involves a benzene (type) ring, and often the terms ortho,
meta and para (meaning 1,2 disubstituted, 1,3 disubstituted and 1,4
disubstituted respectively) are used. These terms are non-IUPAC though.
OH OH OH
Br
CH3
NO2
2-bromophenol 3-methylphenol 4-nitrophenol
ortho-bromophenol meta-methylphenol para-nitrophenol
Solubility of Alcohols
The hydroxyl groups in alcohols can form hydrogen bonds with water, and
many low molecular weight alcohols are miscible with water.
Alcohols are more polar than hydrocarbons, and are better solvents for polar
substances. (E.g. NaCl is partially soluble in Ethanol).
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Acidity of Alcohols and Phenols
Just like water, the hydroxyl groups in alcohols are weakly acidic – strong
bases can generate alkoxide ions.
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The acidities of alcohols vary greatly, depending on the substituents.
Alcohol pKa
Methanol CH3-OH 15.5
Ethanol C2H5-OH 15.9
2-chloroethanol Cl-C2H4-OH 14.3
2,2,2-trifluoroethanol CF3CH2-OH 12.4
t-butylalcohol (CH3)3C-OH 19.0
cyclohexanol C6H11-OH 18.0
phenol C6H5-OH 10.0
Acidity of Phenols
Cyclohexanol and phenol are similar in structure, yet their acidities are very
different. (Phenol is 108 more acidic).
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O-H O-
+ H2O + H3O+ Ka = 10-18
O-H O-
+ H2O + H3O+ Ka = 10-10
The phenoxide ion has resonance stabilization since the negative charge can
be delocalised over 4 atoms (3 carbons and 1 oxygen), making it more
stable.
O- O O O
_ _
Syntheses of Alcohols
Previously seen:
Nucleophilic substitution of alkyl halide with HO-
Acid catalyzed hydration of alkenes
Oxymercuration-demercuration
Hydroboration-oxidation (anti-Markovnikov)
Hydroxylation gives diols (syn – OsO4 : anti – epoxidation-
hydrolysis)
The two most common types of organometallic are Grignard reagents and
organolithium reagents (although there are a variety of others, Cu, Cd, Zn,
Hg, etc).
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C Li C Mg
- + - +
A carbon metal bond is polarized with significant negative charge on the
carbon because metals are so electropositive.
Grignard Reagents
These are of the formal type R-Mg-X where X is usually Br or I.
(CH3CH2)2O
R X + Mg R Mg-X
They are made via the reaction of metallic Mg with the corresponding alkyl
halide, usually in ether type solvents.
This reaction is versatile; primary, secondary and tertiary alkyl halides can
be used, and also vinyl, allyl and aryl halides.
I Mg Mg-I
Ether
Mg
H3C Br H3C Mg-Br
Ether
Organolithium Reagents
These are also formed via action of the metal with an alkyl halide.
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Reaction with Carbonyl Groups
Nucleophilic addition of organometallics to the carbonyl (C=O) group is a
versatile and useful synthetic reaction.
The carbonyl group is strongly polarized, with the oxygen bearing partial
negative charge and the carbon bearing partial positive charge – the carbon
is electrophilic, and therefore attacked by nucleophiles.
- H+
Nuc: C O Nuc O- Nuc OH
1) Ether 2) H3O+
R' - +
C O R' O MgBr R' OH
MgBr
Ketones are compounds that have two alkyl groups bound to the carbonyl
functionality.
Aldehydes have one alkyl group and one hydrogen bound to the carbonyl.
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Formation of Primary Alcohols
1) Ether H
H
CH3-Mg-Br + C O H3C OH
H 2) H3O+ H
methylmagnesium formaldehyde ethanol
bromide
1) Ether CH3
H3C CH3CH2 OH
CH3CH2-Mg-Br C O
H 2) H3O+ H
ethylmagnesium ethanal 2-butanol
bromide
1) Ether CH2CH2CH3
CH3CH2CH2
CH3CH2-Mg-Br C O CH3CH2 OH
H3C 2) H3O+ CH3
ethylmagnesium 2-pentanone 3-methyl-3-hexanol
bromide
Acid Derivatives
Acid chlorides and esters are derivatives of carboxylic acids, where the –OH
group is replaced either by a chlorine atom or an alkoxy group.
O O O
R C OH R C Cl R C O-R'
acid acid chloride ester
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Acid chlorides and esters react with two equivalents of Grignard reagents to
produce tertiary alcohols.
1) Ether R'
R'
2 R-Mg-Br C O R OH
Cl 2) H3O+
R
1) Ether R'
R'
2 R-Mg-Br C O R OH
"RO 2) H3O+
R
The ketone then reacts with the second equivalent of Grignard to give a
tertiary alcohol (as before).
This is a good route to making tertiary alcohols with two identical alkyl
substituents.
E.g.
O
OH
O-CH 3 + 2 CH2CH3MgBr CH2CH3
CH2CH3
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Addition to Ethylene Oxide
Normally ethers do not react with Grignards (use as solvents), but ethylene
oxide is a strained ether (epoxide), and the epoxide ring is opened by
Grignards.
After protonation, the final product is a primary alcohol with two additional
carbon atoms.
Coupling reactions of this type are very common (and useful) in organic
synthesis.
E.g.
Br CH3
+ (CH3)2CuLi
Br CH3
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Reduction of Organometallic Reagents
Organometallics are generally strong nucleophiles and bases – this is both a
blessing and a curse.
Acidic Compounds
Organometallic compounds react with water (moisture).
- CH2CH3
H O H CH3CH2-H + LiOH
+ Li
Mg D2O
Br MgBr D
Besides –OH groups, other acidic groups like N-H and S-H cannot be
tolerated by organometallics.
C N C O C N S O N O
Other groups that are incompatible with Grignards have multiple bonds
involving electronegative elements since these are also attacked by
organometallics.
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Other Reductions of Alkyl Halides
A combination of metals and acids can be used to reduce alkyl halides to
alkanes.
E.g.
Zn
acetic
Br acid H
Hydride Reductions
Lithium aluminum hydride (LiAlH4) is a strong reducing agent, and will
reduce alkyl halides to alkanes.
LiAlH4
Br H
Complex hydrides are the source of hydride ions, and the two most
commonly used reagents are sodium borohydride and lithium aluminum
hydride.
H_ H_
+ +
Na H B H Li H Al H
H H
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Sodium borohydride is the gentler (more selective, safer) reagent of the two.
O
HO
NaBH4 O
O
O
O
LiAlH4 OH
HO
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Catalytic Hydrogenation
Carbonyls can be reduced to alcohols by the addition of hydrogen across the
double bond.
H H2, Ni
O OH
However, C=C double bonds are reduced quicker than C=O double bonds.
Thiols
Thiols are sulfur analogues of alcohols, they contain an –SH group.
They are named using the suffix –thiol, and as a substituent as mercapto-.
Na+ HS-
NaBr
Br SH
[O]
2 RS-H R-S-S-R
[R]
thiol disulfide
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