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• 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
13.2 Acidity of Alcohols and Phenols
Copyright 2012 John Wiley & Sons, Inc.
13 -1

• 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
13 -2

– Resonance
– Explain why phenol is 100 million times more acidic than
cyclohexanol
– Show all relevant resonance contributors
13 -3

• Given the relatively low pKa of phenols, will NaOH be a
strong enough base to deprotonate a phenol?
13 -4

– 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?
13 -5

• 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
13 -6

• 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
13 -7

• Use SCARIO and solvation to rank the following
molecules in order of increasing pKa
13 -8

• 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
13.3 Preparation of Alcohols
13 -9

• 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?
13 -10

• 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
13 -11

• 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?
13.4 Alcohol Prep via Reduction
13 -12

• For oxidation states, we imagine the bonds breaking
heterolytically, and the electrons go to the more
electronegative atom
13 -13

• 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?
13 -14

• 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?
13 -15

• 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)
13 -16

• Reagents that can donate a hydride are generally good
reducing agents
2. Sodium borohydride
13 -17

• Reagents that can donate a hydride are generally good
reducing agents
3. Lithium aluminum hydride (LAH)
13 -18

• 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?
13 -19

• Hydride delivery agents will somewhat selectively
reduce carbonyl compounds
13 -20

• The reactivity of hydride delivery agents can be fine-
tuned by using derivatives with varying R-groups
– Alkoxides
– Cyano
– Sterically hindered groups
13 -21

• LAH is strong enough to also reduce esters and
carboxylic acids, whereas NaBH4 is generally not
13 -22
Will discuss this mechanism in chapter 21

• To reduce an ester, 2 hydride equivalents are needed
13 -23

• To reduce an ester, 2 hydride equivalents are needed
• Which steps in the mechanism are reversible?
13 -24

• Predict the products for the following processes
13 -25

• Diols are named using the same method as alcohols,
except the suffix, “diol” is used
13.5 Preparation of Diols
13 -26

• If two carbonyl groups are present, and enough moles
of reducing agent are added, both can be reduced
13 -27

• Recall the methods we discussed in chapter 9 to
convert an alkene into a diol
13 -28

• 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?
13.6 Grignard Reactions
13 -29

• 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.?
13 -30

• If the Grignard reagent reacts with a carbonyl
compound, an alcohol can result
• Note the similarities between the Grignard and LAH
mechanisms
13 -31

• 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?
13 -32

• 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
13 -33

• Design a synthesis for the following molecules starting
from an alkyl halide and a carbonyl, each having 5
carbons or less
13 -34

• 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
13.7 Protection of Alcohols
13 -35

• A three-step process is required to achieve the desired
overall synthesis
13 -36

• One such protecting group is trimethylsilyl (TMS)
• The TMS protection step requires the presence of a
base. Propose a mechanism
13 -37

• 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
13 -38

• The TMS group can later be removed with H3O+ or F-
• TBAF is often used to supply fluoride ions
13 -39

13 -40
• Practice with conceptual checkpoint 13.18

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

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