1. 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.

2. 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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3. 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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4. 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?
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5. 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?
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6. 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
Copyright 2012 John Wiley & Sons, Inc.

7. 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
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8. 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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9. 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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10. 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?
Copyright 2012 John Wiley & Sons, Inc.

11. 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.

12. 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. 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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14. 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.

15. 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?
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16. 13.4 Alcohol Prep via Reduction
There are three reducing agents you should know
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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17. 13.4 Alcohol Prep via Reduction
Reagents that can donate a hydride are generally good reducing agents
Sodium borohydride
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18. 13.4 Alcohol Prep via Reduction
Reagents that can donate a hydride are generally good reducing agents
Lithium aluminum hydride (LAH)
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19. 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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20. 13.4 Alcohol Prep via Reduction
Hydride delivery agents will somewhat selectively reduce carbonyl compounds
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21. 13.4 Alcohol Prep via Reduction
The reactivity of hydride delivery agents can be fine-tuned by using derivatives with varying R-groups
Alkoxides
Cyano
Sterically hindered groups
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22. 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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23. 13.4 Alcohol Prep via Reduction
To reduce an ester, 2 hydride equivalents are needed
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24. 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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25. 13.4 Alcohol Prep via Reduction
Predict the products for the following processes
Practice with SkillBuilder 13.4
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26. 13.5 Preparation of Diols
Diols are named using the same method as alcohols, except the suffix, “diol” is used
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27. 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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28. 13.5 Preparation of Diols
Recall the methods we discussed in chapter 9 to convert an alkene into a diol
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29. 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?
Copyright 2012 John Wiley & Sons, Inc.

30. 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.

31. 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
Copyright 2012 John Wiley & Sons, Inc.

32. 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.

33. 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.

34. 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.

35. 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
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36. 13.7 Protection of Alcohols
A three-step process is required to achieve the desired overall synthesis
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37. 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
Copyright 2012 John Wiley & Sons, Inc.

38. 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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39. 13.7 Protection of Alcohols
The TMS group can later be removed with H3O+ or F-
TBAF is often used to supply fluoride ions
Copyright 2012 John Wiley & Sons, Inc.

40. 13.7 Protection of Alcohols
Practice with conceptual checkpoint 13.18
Copyright 2012 John Wiley & Sons, Inc.

41. Study Guide for Sections 13.2-13.7
DAY 5, Terms to know:
Sections 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
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

42. 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 a a

43. Prep for Day 6 Must Watch videos: Other helpful videos:
(alcohol substitution reactions, Khan)
(reaction with PBr3, The Organic Chemistry Tutor)
(oxidation of alcohols, Khan)
(biological redox, Khan)
Other helpful videos:
(alcohols, UC-Irvine) start at 20 minute mark
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