Download Chapter 10 Structure and Synthesis of Alcohols

KOT 222 Organic Chemistry II
Chapter 10
Structure and Synthesis
of Alcohols
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What are alcohols??
¾ Organic compounds containing hydroxyl group,
-OH.
¾ Examples:
CH3
CH 3-OH
methanol
CH 3CH 2-OH
H3C
CH
OH
2-propanol
or
Isopropyl alcohol
ethanol
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Structure of Alcohols
R-O-H
H-O-H
¾ Large alkyl group (methyl) increase the C-O-H bond
angle.
¾ C-O bond is longer due to larger covalent radius of
carbon.
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Classification of Alcohols
¾ According to the type of carbinol carbon.
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IUPAC Nomenclature
¾ Find the longest carbon chain containing the
carbon with the -OH group.
¾ Drop the -e from the alkane name, add -ol.
¾ Number the chain, starting from the end
closest to the -OH group.
¾ Number and name all substituents.
1
CH2I CH2 OH
5
CH3
4
3
CH2 CH
2
CH
CH
CH3
CH3
3-(iodomethyl)-2-isopropylpentan-1-ol
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H
For cyclic alcohols:
OH
6
¾ Using prefix cyclo¾ Hydroxyl grop is
assumed on C1.
5
1
4
2
3
H
Br
Trans-2-bromocyclohexan-1-ol
For unsaturated alcohols:
¾ Hydroxyl group takes
precedence.
¾ Assign lowest possible
number to the carbinol
carbon.
¾ Use alkene or alkyne name.
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3
HO
2
1
CH3
4
Cl
H
(E)-4-chlorobut-3-en-2-ol
6
The functional group of alcohols, -OH is not
at the highest-priority!!!
Naming Priority
•
•
•
•
•
•
Acids
Esters
Aldehydes
Ketones
Alcohols
Amines
•
•
•
•
•
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Alkenes
Alkynes
Alkanes
Ethers
Halides
7
When –OH is not the highest-priority functional
group.
¾
-OH is named as a hydroxy substituent.
O
6
5
1
4
2
3
OH
4
CH2OH
2-hydroxymethylcyclohexanone
H
CH3
2
1
CH CH2 C
OH
3-hydroxybutanoic acid
CH2CH2OH
2
3
1
HO
3
O
5
4
H
trans-3-(2-hydroxyethyl)cyclopentanol
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Naming Diols
¾ Diols = alcohols with two –OH groups.
¾ Two numbers are needed to locate the two
-OH groups.
¾ Use -diol as suffix instead of -ol.
OH
OH
OH
OH
Hexane-2,5-diol
Butane-2,3-diol
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Glycols:
¾ Generally means a 1,2-diol, or vicinal diol.
¾ Synthesized by the hydroxylation of alkenes:
CH2
CH2
OH
OH
ethane-1,2-diol
CH2 CH
Common names for glycols
use the name of the alkene
from which they were made.
ethylene glycol
OH
CH3
OH
propane-1,2-diol
propylene glycol
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Naming Phenols
¾ -OH group is assumed to be on carbon 1.
¾ For common names of disubstituted phenols,
use ortho- for 1,2; meta- for 1,3; and para- for
1,4.
¾ Methyl phenols are cresols.
OH
OH
OH
CH3
OH
Cl
3-chlorophenol
2-methylphenol
benzene-1,3-diol
meta-chlorophenol
ortho-cresol
resorcinol
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Physical Properties of Alcohols
¾ Unusually high boiling points due to hydrogen
bonding (together with large dipole moment)
between molecules.
¾ Small alcohols are miscible in water, but
solubility decreases as the size of the alkyl
group increases
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Boiling Points of Alcohols
• Ethanol
: large dipole moment & hydrogen bonding.
• Dimethyl ether : large dipole moment
• Propane
: weak Van der Waals force
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Solubility of Alcohols
R-OH
Solubility decreases as the size of the alkyl
group increases.
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Acidity of Alcohols
¾ pKa range: 15.5-18.0 (water: 15.7)
¾ Acidity decreases as substitution on the alkyl
group increases.
¾ Halogens increase the acidity.
¾ Phenol is much more acidic than openedchain alcohols and is 100 million times more
acidic than cyclohexanol.
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Formation of Alkoxide Ions
¾ Alcohols react with sodium and potassium metal
to form alkoxides.
¾ An oxidation-reduction reaction.
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+ Na
R OH
O- +Na + 1/2 H2 (g)
R
1o/2o alcohol
R3C OH
+ K
R 3C
O- + K
+ 1/2 H2 (g)
3o alcohol
R OH
+ NaH
OH
+
THF
R
O- +Na + H2 (g)
O-+Na
NaOH
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+ H2 O
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Synthesis of Alcohols - Review
¾ Nucleophilic substitution on alkyl halides:
¾ From alkenes:
1. Acid-catalyzed hydration:
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2. Oxymerculation-demerculation:
3. Hydroboration-oxidation
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4. Hydroxylation: Synthesis of glycols
• Syn hydroxylation of alkenes
– osmium tetroxide, hydrogen peroxide
– cold, dilute, basic potassium permanganate.
• Anti hydroxylation of alkenes
– peroxyacids, hydrolysis
O
R
C
C
OH
+
OOH , H3O
C
C
C
OH
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¾ Addition of acetylides to carbonyl compounds
R
R
R
C
C
+
C
O
R'
acetylide
ketone/aldehyde
R
C
C
C
R'
alkoxide
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R
+
O
H3O
R
C
C
C
OH
R'
acetylenic alcohol
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Organometallic Reagents for
Alcohol Synthesis
¾ What are organometallic reagents?
compounds contain covalent bonds between
carbon atoms and metal atoms.
δ-
δ+
C-M
¾ An example is sodium acetylide.
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Organometallic compound – sodium acetylide
¾ Nucleophilic carbon can attack a partially
positive carbon:
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How about alkyl and alkenyl groups?
¾ Can be made into
1. Grignard Reagents
2. Organolithium reagents
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1. Grignard Reagents
¾ Organomagnesium halides.
¾ Formula R-Mg-X (reacts like R:- +MgX).
¾ Stabilized by anhydrous ether.
¾ From the reaction between alkyl halides and
magnesium metal.
¾ reactivity for alkyl halides is R-I > R-Br > R-Cl >>
R-F
¾ May be formed from any halide:
- primary
- vinyl
- secondary
- aryl
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- tertiary
CHEMISTRY II
Formation of Grignard reagents:
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2. Organolithium Reagents
¾ Formula R-Li (reacts like R:- +Li)
¾ Can be produced from alkyl, vinyl, or aryl
halides, just like Grignard reagents.
¾ Ether not necessary, wide variety of solvents
can be used.
R
Li+ -X + R
X + 2 Li
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Li
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Addition of Organometallic Reagents to
Carbonyl Compounds
δ-
δ+
R – Mg - X
δ-
δ+
R – Li
¾ Organometallics are strong nucleophiles and
strong bases.
¾ Attack the C=O group: nucleophilic addition.
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0
Formation of 1 Alcohols
• Reaction of a Grignard with formaldehyde
will produce a primary alcohol after
protonation.
magnesium alkoxide salt
H
CH3CH2CH2CH2 MgBr +
H
H
1. ether
C O
2. H3O
butylmagnesium bromide
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+
CH3CH2CH2CH2 C OH
H
1-pentanol
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Formation of 20 Alcohols
¾ Addition of a Grignard reagent to an aldehyde
followed by protonation will produce a secondary
alcohol.
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0
Formation of 3 Alcohols
¾ by addition of a Grignard to a ketone followed
by protonation with dilute acid.
O
C
CH3
+
CH3CH2MgBr
O
C
CH3
CH2CH3 + CH3MgBr
1. ether
2. H3O
C
OH
+
CH2CH3
O
MgBr
+
CH3
C
CH2CH3
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Grignard Reactions with Acid
Chlorides and Esters
¾ Use two equivalents of Grignard reagents.
¾ The product is a tertiary alcohol with
two identical alkyl groups.
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Addition of first equivalent of Grignard reagent:
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Addition of second equivalent of Grignard reagent:
ketone
alkoxide
tertiary alcohol
¾ The final product is a tertiary alcohol.
¾ One of the alkyl groups (R’) is from acid chloride
or ester and the other two (R) are from Grignard
reagent.
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Grignard Reagents with Ethylene Oxide
¾ Grignard reagents do not react with ethers but
they do react with epoxides and open them to
form alcohols.
¾ The ring strain present in the epoxide is relieved
by the opening.
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Summary of Grignard Reactions
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Limitations of Organometallic Reactions
¾
¾
1.
Grignard and organolithium are strong nucleophiles and
bases
They can react with acidic or electrophilic compounds.
Grignard (and organolithium) reagents can be
protonated by water and destroyed, become alkanes.
other acidic protons: O-H, N-H, S-H, -C≡C-H.
R-X + Mg → R-Mg-X + H-O-H → R-H + XMgOH
H-O-H
R-X + 2 Li → RLi + LiX →
R-H + LiOH
A reaction to convert (reduce) an alkyl halide to an alkane
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2. No other electrophilic multiple bonds, like C=N,
C≡N, S=O, or N=O in the solvent or in the
Grignard reagent itself.
O
MgBr
CH3CCH3, H3O+
X
O
1. CH3CH2MgBr
2. H3O+
X
OH
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OH
HO
CH2CH3
OH
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Coupling Reactions
¾ Formation of carbon – carbon bond.
¾ Use an organocopper reagent, lithium
dialkylcuprate (Gilman reagent).
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Reduction of Carbonyl Groups
¾ Carbonyl compounds can be reduced into
alcohols.
™ Reduction of aldehyde yields 1º alcohol.
™ Reduction of ketone yields 2º alcohol.
¾ Reducing agents:
™ Sodium borohydride, NaBH4
™ Lithium aluminum hydride, LiAlH4
™ Raney nickel
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Uses of sodium borohydride:
¾ Hydride ion, H-, attacks the carbonyl carbon,
forming an alkoxide ion.
¾ Then the alkoxide ion is protonated by dilute
acid.
¾ Only reacts with carbonyl of aldehyde or ketone,
not with carbonyls of esters or carboxylic acids.
O
O
CH2 C OCH3
NaBH4
HO
O
CH2 C OCH3
H
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Uses of lithium aluminium hydride:
¾Stronger reducing agent.
¾Dangerous!!! Reacts explosively with
water and alcohols.
¾Reduces: Ketone → 2o alcohol
aldehyde
1o alcohol
carboxylic acid
ester
O
O
1. LiAlH4
CH2 C OCH3
2. H3O
+
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HO
CH2 CH2 OH
H
43
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Uses of Raney nickel ( catalytic
hydrogenation)
¾ Raney nickel: an effective catalyst for the
hydrogenation of aldehydes and
ketones to alcohols.
¾ Alkene double bonds will be reduced as well.
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Thiols (Mercaptans)
¾ Sulfur analogues of alcohols:
R-SH
R-OH
¾ Functional group, -SH is called sulfhydryl group.
¾ Naming by using the suffix -thiol.
CH3 SH
CH3CH CHCH2 SH
HS CH2CH2 OH
methanethiol
methyl mercaptan
2-butane-1-thiol
2-marcaptoethanol
¾ Able to complex with heavy metals: arsenic,
mercury….
¾ Stink!!!
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Acidity of thiols:
¾ More acidic than alcohols because:
™ S-H bonds are weaker than O-H bonds.
™ Negative charge can be delocalized over a
larger region in thiolate ion as compared to
alkoxide ion.
CH3CH2
OH +
OH
CH3CH2 O-
+
OH
CH3CH2 S-
+
-
H2 O
ethanol, pKa = 15.9
CH3CH2 SH +
-
H2 O
ethanethiol, pKa= 10.5
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Synthesis of thiols:
¾ By SN2 reactions of sodium hydrosulfide with unhindered
alkyl halides.
¾ Thiols are easily oxidized (mild) into a dimer called
disulfide.
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¾ Strong oxidation converts thiols to sulfonic acids,
R-SO3H.
O
R
S
H
KMnO4
R
S
O
O
H
or HNO3
R
O
S
O
O
H
R
O
vigorous
oxidation (boil)
S
2+
O
H
O
sulfonic acid
O
SH
HNO3
S
(boil)
OH
O
benzenethiol
benzenesulfonic acid
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