13.2 Acidity of Alcohols and Phenols
•
A strong base is usually necessary to deprotonate an
alcohol
•
A preferred choice to create an alkoxide is to treat the
alcohol with Na, K, or Li metal. Show the mechanism
for such a reaction
•
Practice with conceptual checkpoint 13.4
Copyright 2012 John Wiley & Sons, Inc.
13 -1
13.2 Acidity of Alcohols and Phenols
•
•
Recall from chapter 3 how ARIO is used to qualitatively
assess the strength of an acid
Lets apply these factors to alcohols and phenols
–
Atom
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13 -2
13.2 Acidity of Alcohols and Phenols
•
Lets apply these factors to alcohols and phenols
–
Resonance
–
Explain why phenol is 100 million times more acidic than
cyclohexanol
Show all relevant resonance contributors
–
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13.2 Acidity of Alcohols and Phenols
•
Given the relatively low pKa of phenols, will NaOH be a
strong enough base to deprotonate a phenol?
Copyright 2012 John Wiley & Sons, Inc.
13 -4
13.2 Acidity of Alcohols and Phenols
•
Lets apply these factors to alcohols and phenols
–
Induction: unless there is an electronegative group nearby,
induction won’t be very significant
–
Orbital: in what type of orbital do the alkoxide electrons
reside? How does that effect acidity?
Copyright 2012 John Wiley & Sons, Inc.
13 -5
13.2 Acidity of Alcohols and Phenols
•
•
•
Solvation is also an important factor that affects acidity
Water is generally used as the solvent when measuring
pKa values
Which of the alcohols below is stronger?
•
ARIO can not be used to explain the difference
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13 -6
13.2 Acidity of Alcohols and Phenols
•
Solvation explains the difference in acidity
•
Draw partial charges on the solvent molecules to show
why solvation is a stabilizing effect
Practice with SkillBuilder 13.2
•
Copyright 2012 John Wiley & Sons, Inc.
13 -7
13.2 Acidity of Alcohols and Phenols
•
Use SCARIO and solvation to rank the following
molecules in order of increasing pKa
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13.3 Preparation of Alcohols
•
•
•
We saw in chapter 7 that substitution reactions can
yield an alcohol
What reagents did we use to accomplish this
transformation?
We saw that the substitution can occur by SN1 or SN2
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13 -9
13.3 Preparation of Alcohols
•
•
The SN1 process generally uses a weak nucleophile
(H2O), which makes the process relatively slow
Why isn’t a stronger nucleophile (-OH) used under SN1
conditions?
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13 -10
13.3 Preparation of Alcohols
•
In chapter 9, we learned how to make alcohols from
alkenes
•
Recall that acid-catalyzed hydration proceeds through a
carbocation intermediate that can possibly rearrange
How do you avoid rearrangements?
Practice with checkpoints 13.7 and 13.8
•
•
Copyright 2012 John Wiley & Sons, Inc.
13 -11
13.4 Alcohol Prep via Reduction
•
•
•
•
A third method to prepare alcohols is by the reduction
of a carbonyl. What is a carbonyl?
Reductions involve a change in oxidation state
Oxidation state are a method of electron bookkeeping
Recall how we used formal charge as a method of
electron bookkeeping
–
–
Each atom is assigned half of the electrons it is sharing with
another atom
What is the formal charge on carbon in methanol?
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13 -12
13.4 Alcohol Prep via Reduction
•
For oxidation states, we imagine the bonds breaking
heterolytically, and the electrons go to the more
electronegative atom
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13 -13
13.4 Alcohol Prep via Reduction
•
•
•
•
•
Each of the carbons below have zero formal charge, but
they have different oxidation states
Calculate the oxidation number for each
Is the conversion from formic acid  carbon dioxide an
oxidation or a reduction?
What about formaldehyde  methanol?
Practice with SkillBuilder 13.3
Copyright 2012 John Wiley & Sons, Inc.
13 -14
13.4 Alcohol Prep via Reduction
•
The reduction of a carbonyl requires a reducing agent
•
•
Is the reducing agent oxidized or reduced?
If you were to design a reducing agent, what element(s)
would be necessary?
Would an acid such as HCl be an appropriate reducing
agent? WHY or WHY NOT?
•
Copyright 2012 John Wiley & Sons, Inc.
13 -15
13.4 Alcohol Prep via Reduction
•
There are three reducing agents you should know
1. We have already seen how catalyzed hydrogenation can
reduce alkenes. It can also work for carbonyls
–
Forceful conditions (high temperature and/or high pressure)
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13 -16
13.4 Alcohol Prep via Reduction
•
Reagents that can donate a hydride are generally good
reducing agents
2. Sodium borohydride
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13 -17
13.4 Alcohol Prep via Reduction
•
Reagents that can donate a hydride are generally good
reducing agents
3. Lithium aluminum hydride (LAH)
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13 -18
13.4 Alcohol Prep via Reduction
•
•
Note that LAH is significantly more reactive that NaBH4
LAH reacts violently with water. WHY?
•
How can LAH be used with water if it reacts with water?
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13 -19
13.4 Alcohol Prep via Reduction
•
Hydride delivery agents will somewhat selectively
reduce carbonyl compounds
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13 -20
13.4 Alcohol Prep via Reduction
•
The reactivity of hydride delivery agents can be finetuned by using derivatives with varying R-groups
–
–
–
Alkoxides
Cyano
Sterically hindered groups
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13 -21
13.4 Alcohol Prep via Reduction
•
LAH is strong enough to also reduce esters and
carboxylic acids, whereas NaBH4 is generally not
Will discuss this mechanism in chapter 21
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13 -22
13.4 Alcohol Prep via Reduction
•
To reduce an ester, 2 hydride equivalents are needed
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13 -23
13.4 Alcohol Prep via Reduction
•
To reduce an ester, 2 hydride equivalents are needed
•
Which steps in the mechanism are reversible?
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13 -24
13.4 Alcohol Prep via Reduction
•
Predict the products for the following processes
•
Practice with SkillBuilder 13.4
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13 -25
13.5 Preparation of Diols
•
Diols are named using the same method as alcohols,
except the suffix, “diol” is used
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13.5 Preparation of Diols
•
If two carbonyl groups are present, and enough moles
of reducing agent are added, both can be reduced
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13.5 Preparation of Diols
•
Recall the methods we discussed in chapter 9 to
convert an alkene into a diol
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13.6 Grignard Reactions
•
•
•
Grignard reagents are often used in the synthesis of
alcohols
To form a Grignard, an alkyl halide is treated with Mg
metal
How does the oxidation state of the carbon change
upon forming the Grignard?
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13 -29
13.6 Grignard Reactions
•
The electronegativity difference between C (2.5) and
Mg (1.3) is great enough that the bond has significant
ionic character
•
The carbon atom is not able to effectively stabilize the
negative charge it carries
Will it act as an acid, base, electrophile, nucleophile,
etc.?
•
Copyright 2012 John Wiley & Sons, Inc.
13 -30
13.6 Grignard Reactions
•
If the Grignard reagent reacts with a carbonyl
compound, an alcohol can result
•
Note the similarities between the Grignard and LAH
mechanisms
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13 -31
13.6 Grignard Reactions
•
Because the Grignard is both a strong base and a strong
nucleophile, care must be taken to protect it from
exposure to water
•
If water can’t be used as the solvent, what solvent is
appropriate?
What techniques are used to keep atmospheric
moisture out of the reaction?
•
Copyright 2012 John Wiley & Sons, Inc.
13 -32
13.6 Grignard Reactions
•
Grignard examples
•
With an ester substrate, excess Grignard reagent is
required. WHY? Propose a mechanism
List some functional groups that are NOT compatible
with the Grignard
Practice with SkillBuilder 13.5
•
•
Copyright 2012 John Wiley & Sons, Inc.
13 -33
13.6 Grignard Reactions
•
Design a synthesis for the following molecules starting
from an alkyl halide and a carbonyl, each having 5
carbons or less
Copyright 2012 John Wiley & Sons, Inc.
13 -34
13.7 Protection of Alcohols
•
Consider the reaction below. WHY won’t it work?
•
The alcohol can act as an acid, especially in the
presence of reactive reagents like the Grignard reagent
The alcohol can be protected to prevent it from reacting
•
Copyright 2012 John Wiley & Sons, Inc.
13 -35
13.7 Protection of Alcohols
•
A three-step process is required to achieve the desired
overall synthesis
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13.7 Protection of Alcohols
•
One such protecting group is trimethylsilyl (TMS)
•
The TMS protection step requires the presence of a
base. Propose a mechanism
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13 -37
13.7 Protection of Alcohols
•
•
Evidence suggests that substitution at the Si atom
occurs by an SN2 mechanism
Because Si is much larger than C, it is more open to
backside attack
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13 -38
13.7 Protection of Alcohols
•
•
The TMS group can later be removed with H3O+ or FTBAF is often used to supply fluoride ions
Copyright 2012 John Wiley & Sons, Inc.
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13.7 Protection of Alcohols
•
Practice with conceptual checkpoint 13.18
Copyright 2012 John Wiley & Sons, Inc.
13 -40
Study Guide for Sections 13.2-13.7
DAY 5, Terms to know:
Sections 13.2-13.7 induction, solvation, carbonyl, oxidation, reduction, oxidation state, heterolytic,
reducing agent, hydride, LAH, carboxylic acid, ester, oxidizing agent, peracid, diol, syn addition, anti
addition, Grignard reagent, protecting group, TBAF
DAY 5, Specific outcomes and skills that may be tested on exam 1:
Sections 13.2-13.7
•Be able to use both SCARIO for qualitative analysis of acidity and pKa for quantitative analysis of acidity
•Given relevant pKa values, be able to determine whether a specific base will be able to deprotonate a
specific alcohol or phenol
•Be able to determine oxidation numbers for atoms involved in organic compounds
•Be able to choose appropriate reagents for the reduction of a specific carbonyl group to produce an
alcohol
•Given a specific carbonyl and specific reducing reagents, be able to predict the products of the reaction
and draw a complete mechanism
•Be able to choose appropriate reagents for the addition across a C=C to produce either a syn or anti 1,2
diol
•Given a specific alkene and specific reagents, be able to predict the products of an addition reaction
giving an alcohol or a diol and draw a complete mechanism
•Be able to choose appropriate reagents for a Grignard reaction to produce a specific alcohol
•Given a specific carbonyl and specific Grignard reagent, be able to predict the products of the reaction
and draw a complete mechanism
•Be able to give an appropriate solvent for a Grignard reaction and describe techniques that can be used
to prevent moisture from reaching the reaction
Be able to describe what a protecting group is and give an example when one might be useful in a
synthesis
•Be able to predict the characteristics of peaks in IR, NMR, and MS data obtained for alcohols
•Be able to give a reasonable structure for a compound given some combination of IR, NMR, and MS data
Extra Practice Problems for Sections 13.2-13.7
Complete these problems outside of class until you are confident you have
learned the SKILLS in this section outlined on the study guide and we will
review some of them next class period. 13.4a 13.5 13.6 13.7 13.8 13.9
13.10 13.12 13.13 13.14 13.15 13.16 13.17 13.18a 13.33 13.34
13.53 13.54 13.55 13.56
Prep for Day 6
Must Watch videos:
https://www.youtube.com/watch?v=KPh60w6McPI (alcohol substitution reactions, Khan)
https://www.youtube.com/watch?v=YLblFkbYWqc (reaction with PBr3, The Organic Chemistry Tutor)
https://www.youtube.com/watch?v=j-rBgs_p-bg (oxidation of alcohols, Khan)
https://www.youtube.com/watch?v=0w96SqrvVjw (biological redox, Khan)
Other helpful videos:
http://ocw.uci.edu/lectures/chem_51b_lec_15_organic_chemistry_reduction_and_oxidization_part_3.ht
ml (alcohols, UC-Irvine) start at 20 minute mark
Read Sections 13.8-13.13