Learning Guide for Chapter 14 - Alcohols (I)
I. Introduction to Alcohols and Thiols
II. Acid/base Behavior of Alcohols, Phenols, and Thiols
III. Nomenclature of Alcohols
IV. Synthesis of Alcohols
Previous reactions
Reduction of C=O functional groups
Organometallic reagents
I. Introduction to Alcohols and Thiols
What does an alcohol functional group look like?
OH
O
How are alcohols different from carboxylic acids?
OH
carboxylic acids ahve
C=O on same carbon as
OH, alcohols do not
What are some common alcohols?
methanol
ethanol
isopropanol
CH3OH
wood alcohol; race car fuel; poisonous - causes blindness,
then death; treatment - IV of ethanol
grain alcohol; found in alcoholic beverages; comes from
fermenting sugars and starches; denatured for use in labs;
poisonous over time or in high doses
OH
OH
found in rubbing alcohol; used in first aid for disinfecting
What does a thiol functional group look like?
What other name are they known by?
SH
mercaptan - captures mercury
Why is their reactivity similar to alcohols?
What is the main difference in their reactivity?
S and O are in the same family
size - S is larger than O
thiols are more acidic, stronger Nu
LG Ch 14 p 2
What is the most noticeable characteristic of thiols?
strong, disagreeable odor
What are some examples of this?
SH
SH
SH
natural gas additive
Is this always the case?
skunk odor
no
SH
grapefruit mercaptan - citrusy smell
Classification of Alcohols
How are alcohols in which the carbon is sp3 hybridized classified? 1o, 2o, 3o
OH
2o
OH
3o
OH
1o
How are alcohols in which the carbon is sp2 hybridized classified? enols or aryl alcohols
OH
OH attached to C=C
O
tautomerize to form C=O
enol
OH
aryl alcohol
OH
phenol
OH directly attached to benzene ring
other aryl alcohols are
sometimes called phenols
How would the following compounds be classified?
OH
OH
allyl alcohol
unsaturated alcohol
not an enol
aromatic alcohol
not an aryl alcohol
LG Ch 14 p 3
Physical Properties of Alcohols
Match up the following compounds with their boiling points and justify your answers.
similar masses
dipole forces
bp -42oC
ethyl fluoride
hydrogen bonding ethanol
Van der Waals
bp -38 oC
bp -38 oC
F
OH
bp 78oC
bp 78oC
much higher!
bp -42oC
propane
Which of the following would you expect to be soluble in water?
OH
CH3OH
OH
OH
OH
HO
OH
HO
OH
OH
OH
OH
soluble: 1-4 carbons with one OH; up to at least 6 C's with more than one OH
IR Spectra of Alcohols
Is IR a good way to identify alcohols?
yes
Label the important bands in the following spectrum.
O-H
C-H
3400-3200 cm-1
CH2 C-O
bending
1300-1000 cm-1
OH
LG Ch 14 p 4
NMR Spectra of Alcohols
H
Consider the following compound.
H
OH
Where should you look for the H's next to the OH? 3-4 ppm, triplet
Where should you look for the OH peak? 1-5 ppm, broad singlet
What will happen if D2O is added to this sample? OH disappears
DHO peak appears
Label the peaks in the following spectrum.
OH
a - 5H, m, 7ppm
b - 2H, t, 2-3 ppm
c - 2H, t, 3-4 ppm
d - 1H, s, 1-5 ppm
a>c>b>d
II. Acid-base Behavior of Alcohols, Phenols, and Thiols
What happens when an alcohol reacts with an acid?
base
OH
acid
H-base
pKa -2.4
OH2
+
base
pKa < -2.4 protonated alcohol
What kind of acid would be required for this reaction to have a favorable equilibrium?
pKa less than 2.4
H2SO4 -10
HI -9
HBr -8
HCl -7
What would happen if the protonated alcohol came in contact with a base?
OH2
NaOH
OH
+ H2O
it would be protonated
LG Ch 14 p 5
What happens when an alcohol reacts with an base?
pKa > 18
pKa 16-18
OH
base
+ H-base
O
alkoxide
acid
What kind of base would be required for this reaction to have a favorable equilibrium?
pKa of the conjugate acid must be greater than 18
most commonly used base - NaH - pKa 36
How can alkali metals be used to form alkoxides?
by a redox reaction
1o
3o
OH
OH
Na
O
K
O
Na
+ 1/2 H2
Na - methyl, 1o
o o
+ 1/2 H2 K - 2 , 3
(Na too slow)
K
remember our friend from E2?
What would happen if an alkoxide came in contact with an acid?
O
HCl
OH
Cl
it would be protonated
What would happen if a protonated alcohol and an alkoxide were reacted with each other?
O
+
OH2
2
they would neutralize each other
How does the acidity of alcohols vary?
methyl > 1o > 2o > 3o
OH
pKa 15.9
OH
pKa 16.5
OH
pKa 18.0
OH
LG Ch 14 p 6
Why are aryl alcohols more acidic than aliphatic alcohols?
conjugate base is stabilized by resonance
OH
O
O
base
O
O
greatest
resonance
contributor
pKa 10.0
+ H-base
Could NaOH be used as the base?
yes
O
OH
+
NaOH
+ H2O
products
favored
pKa 10.0
pKa 15.7
stronger acid
Why won't this work with regular alcohols? alcohols not acidic enough
O
OH
+
NaOH
+ H2O
pKa 15.7
stronger acid
pKa 17
Why are thiols more acidic than alcohols?
sulfur is larger than oxygen, H is further away, easier to remove
base
SH
S
pKa 10.5
+ H-base
thiolate ion
Could NaOH be used as the base?
S
SH
+
pKa 10.5
stronger acid
yes
NaOH
+ H2O
pKa 15.7
reagents
favored
LG Ch 14 p 7
III. Nomenclature of Alcohols
Common names
Based on the common name for the following alkyl halide, deduce the common name of the
alcohol shown.
Br
propyl bromide
OH
propyl alcohol
name of substituent + "alcohol"
Give the common names of the following alcohols.
methyl alcohol
CH3OH
ethyl alcohol
OH
OH
OH
isopropyl alcohol
OH
isobutyl alcohol
OH
sec-butyl alcohol
tert-butyl alcohol
OH
cyclopentyl alcohol
O
OH
OH
allyl alcohol
OH
H
vinyl alcohol
unstable
OH
benzyl alcohol
phenol
IUPAC names
What are the four steps in naming an organic compound?
1.
Determine stereochemistry, if any.
2.
Choose the principle chain, give it a name.
3.
Number the principle chain.
4.
Name the substituents, alphabetize them, add them to the name.
LG Ch 14 p 8
What are the priorities for choosing the principle chain?
1. must contain the alcohol (or as many as possible)
2. double or triple bonds
3. longest chain
4. most substituents
HO
OH
OH
How does the alkane name change for each of the following?
OH
pentane
pentanol
drop "e", add "ol"
OH
cyclohexane
OH
cyclohexene
cyclohexenol
hexane
hexadiene
drop "ane" add "adiene"
pentane
pentanediol
use entire alkane name, add "diol"
OH
What are the priorities for numbering the principle chain?
1.
lowest number to alcohol(s)
2.
lowest number to double or triple bonds
3.
lowest numbers to substituents (first point of difference)
4.
lowest number to first substituent alphabetically
LG Ch 14 p 9
Number the following compounds.
HO
2
6
OH
2
1
3
5
1
4
5
3
OH
4
3
1
2
4
If you have to name an alcohol as a substituent, what is it called?
hydroxy
OH
OH
2-(1-hydroxyethyl)-1-cyclopentanol
Draw structures for the following names.
2-cyclohexyl-1-butanol
1,3-cyclopentanediol
5-bromo-4-methyl-2-hexanol
OH
OH
OH
HO
2-cyclopenten-1-ol
Br
2-(1-hydroxyethyl)-1-cyclohexanol
5-methyl-3-hexanol
OH
OH
OH
OH
Give the names of the following compounds.
OH
2,3-pentanediol
(3S,4S)-4-methyl-3-hexanol
OH
OH
OH
OH
OH
trans-3-penten-2-ol
4-(2-hydroxypropyl)-1-cyclohexanol
LG Ch 14 p 10
IV. Synthesis of Alcohols
Reactions from Previous Chapters
What reagents would be required to convert the following compounds to alcohols using the
reaction given?
NaOH
SN2 reactions
Br
1o RX to ROH
OH
1o
H2SO4
Acid-catalyzed hydration
OH
H2O
OH
1. Hg(OAc)2, H2O
Oxymercuration-reduction
2. NaBH4
C=C to ROH
1. BH3-THF
Hydroboration-oxidation
OH
2. H2O2,
Hydroxylation
C=C to ROH
KMnO4, KOH, H2O
or OsO4, H2O2
OH-
C=C to ROH
OH
C=C to vicinal diol
OH
In this chapter, we will learn two more:
reduction of a C=O by adding hydrogen
O
H
HO
ketones
aldehydes
carboxylic acids
esters
to ROH
reduction of a C=O by adding an alkyl group
O
HO
R
ketone
aldehyde
to ROH
ester
acid chloride
LG Ch 14 p 11
Reduction of C=O groups to form alcohols
How is oxidation defined in organic chemistry?
gaining bonds to O and/or losing bonds to H
How is reduction defined in organic chemistry?
losing bonds to O and/or gaining bonds to H
Which of these is occurring in the following reactions, and why?
OH
KMnO4
both C's gain bonds to O
H2O, KOH
1. BH3-THF
2. H2-O2,
OH-
OH
oxidation
OH
H
one C gains bond to O,
one C gains bond to H
no net change in oxidation state
H
H2, Pd/C
H
both C's gain bonds to H
reduction
What type of alcohol can be formed by the reduction of the following compounds?
lose a bond to O, gain a bond to H
O
reduction
aldehyde
OH
1o alcohol
H
ketone
carboxylic
acid
O
reduction
O
reduction
2o alcohol
OH
1o alcohol
OH
O
ester
OH
reduction
O
OH
+
OH
2 alcohols
LG Ch 14 p 12
Which of the following reagents is effective in reducing the functional groups shown?
C
C
C
C
to
C
C
ketone, aldehyde
C O to C OH
COOH, ester
C O to C OH
H2, Pd/C
yes
no
no
NaBH4
no
yes
no
most common
reagent for ald/ket
LiAlH4
no
yes
yes
Raney Ni
yes
yes
no
most common
reagent for ester,
COOH
Which is more reactive, NaBH4 or LiAlH4? Why?
H
NaBH4 = H B
Na
H
H
Li
LiAlH4 = H Al H
Al-H bond weaker than B-H
H
H
less reactive
solvent - methanol
more reactive
solvent - ether
How do they react?
H
H
B
Na
H
!-
O
NaBH4
!+ H
CH3OH
H
H
Li
H Al H
H
O
LiAlH4
H
2. H3O+
O
H
Na
H
H
H
Li
O
OH
H
H
OH
H
H
What is Raney Ni? What is the advantage of using it?
Ni catalyst with H2 molecules absorbed onto it
it will also reduce C=C and C---C if they are present
What safety hazards exist with these materials?
LiAlH4 reacts vigorously with water, releases H2, can cause lab fires
Raney Ni is pyrophoric - spontaneously ignites in air
both steps
taking place in
the reaction
first step has
to finish, then
add acid for
second step
LG Ch 14 p 13
What reagent(s) could be used to accomplish the following reactions?
* NaBH4, CH3OH
4 functional groups
O
or Raney Ni
or LiAlH4, 2) H3O+
O
ketone --> 2o alcohol
OH
LiAlH4, 2) H3O+
OH
COOH --> 1o alcohol
OH
O
* NaBH4, CH3OH
OH
H
aldehyde --> 1o alcohol
or Raney Ni
or LiAlH4, 2) H3O+
O
LiAlH4, 2) H3O+
O
O
* NaBH4, CH3OH
C=O vs C=C
H
O
ketone vs ester
O
reduce aldehyde, leave C=C
reduce both aldehyde and C=C
OH
H2, Pd/C
O
reduce C=C, leave aldehyde
H
LiAlH4, 2) H3O+
OH
OH
+
O
O
O
* NaBH4, CH3OH
O
O
OH
O
can't be done!
reduce both
ketone and ester
HO
O
reduce ketone,
leave ester
O
or Raney Ni
O
O
ester --> 2 alcohols
OH
Raney Ni
H
O
OH
or LiAlH4, 2) H3O+
H
O
HO
OH
+
HO
reduce ester,
leave ketone
LG Ch 14 p 14
Addition of Organometallic Reagents to C=O Groups to form Alcohols
What is the advantage of using an organometallic reagent instead of a reducing agent to
convert a C=O group to an alcohol?
reducing agent - same carbon structure
organometallic reagent - new carbon group added
What are the two most common kinds of organometallic reagents used in organic
chemistry?
!- !+
Grignard reagents
MgBr
!+
Li
organolithium reagents
!-
What polarity do these reagents have? How reactive are they, and why?
C - partially negative
highly reactive - C doesn't like to be -, usually formed and used, not stored
How are organometallic reagents formed?
alkyl halide + metal
Br
Mg
MgBr
ether
Cl
Li
2 Li
+ LiCl
ether
What other kinds of halides can be used?
vinyl halides
Cl
Mg
ether
Br
aryl halides
2 Li
ether
MgCl
Li
+ LiBr
LG Ch 14 p 15
What are the two ways in which a Grignard or organolithium reagent can react?
base
MgBr
H-base
H
+
Mg
Nu
MgBr
E
E
+
Mg
Br
+
base
Br
How strong of bases are organometallic reagents? Why is this so?
conjugate acid - alkane
pKa ~50
weakest acid - strongest base!
C has low EN, unstable with partial neg charge
What would happen if an organometallic reagent came in contact with water?
it would be protonated
Li
H
O
H
H
+
Li
O
H
What other kinds of compounds will react as acids with organometallic reagents?
alcohols, amines, amides, carboxylic acids, terminal alkynes
If this usually a reaction we desire?
no - it ruins our reagent!
Is there any way in which it could be useful?
converts RX to alkane
Br
MgBr
CH3OH
Mg
+ CH3O
ether
Mg
Br
adds a D
Li
Cl
2 Li
hexanes
D
D2O
+ LiOD
LG Ch 14 p 16
In the absense of any compounds with acidic H's, organometallic reagents react as
nucleophiles.
What type of compound will be formed when a Grignard or organolithium reagent is
reacted with an aldehyde or ketone, followed by mild, aqueous acid?
attack-push up
O
Mg
Br
O
H
2. H3O+
aldehyde
OH
MgCl
protonate
react once
2o alcohol
O
Li
O
Li
OH
2. H3O+
ketone
3o alcohol
Is there any way to get a primary alcohol?
MgBr
O
Mg
OH
Br
O
H
H
2. H3O+
formaldehyde
1o alcohol
What type of compound will be formed when a Grignard or organolithium reagent is
reacted with an acid chloride, following by mild, aqueous acid?
can't stop here!
attack-push up
push off
reacts twice
O
O
Cl
2 eq
MgCl
O
Cl
+
Cl
2. H3O+
acid chloride
OH
protonate
3o alcohol w/2 identical groups
Why doesn't this happen with aldehydes and ketones?
no leaving group
O
attack-push up
LG Ch 14 p 17
What will happen to an ester?
same thing
reacts twice
O
Li
2
O
O
O
2. H3O+
O
+
O
Li
OH
+
O
HO
reacts once
What type of compound is formed when a Grignard or organolithium reagent is reacted
with ethylene oxide?
protonate
attack-push off
O
Li
OH
O
adds 2 C's
2. H3O+
What reagents would be needed to complete the following reactions?
OH
O
H
H3C
MgBr
2. H3O+
2. H3O+
O
H3C
H
MgBr
O
OH
MgBr
H
H
2. H3O+
O+
2. H3
O
Li
O
Li
OH
O
2. H3O+
2. H3O+
How could the following compound be synthesized?
OH
O
+
H3C
Li
MgBr
2. H3O+
H
2o alcohol - RM + ald
OH
Li
O
+
O
H
2. H3O+
OH
OH
LG Ch 14 p 18
Summary of methods for synthesizing alcohols:
SN2:
1o alkyl halide + NaOH --> 1o alcohol
Acid-catalyzed hydration:
alkene + H2SO4 + H2O --> 2o or 3o alcohol
(more substituted side, rearrangments possible)
Oxymercuration-reduction:
alkene + 1. Hg(OAc)2, H2O 2. NaBH4 --> 2o or 3o alcohol
(more substituted side, no rearrangements)
Hydroboration-oxidation:
alkene + 1. BH3-THF, 2. H2O2, NaOH --> 1o or 2o alcohol
(less substituted side, no rearrangements)
Reduction of an aldehyde or ketone:
aldehyde or ketone + NaBH4, CH3OH --> 1o or 2o alcohol
Reduction of a carboxylic acid or ester:
carboxylic acid or ester + LiAlH4 --> 1o alcohol
(ester has a second alcohol)
Addition of an organometallic reagent to an aldehyde or ketone
aldehyde or ketone + Grignard or organolithium reagent, 2. H3O+ --> 2o or 3o
alcohol
Addition of an organometallic reagent to and acid chloride or ester:
acid chloride or ester + Grignard or organolithium reagent, 2. H3O+ -->
3o alcohol with two identical groups
Addition of an organometallic reagent to an epoxide:
ethylene oxide + Grignard or organolithium reagent, 2. H3O+ --> 1o alcohol