c341 f2011 chapter 13 alcohols - chemistry courses:...

C341/Fall 2011 Chapter 13

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Chapter 13 Outline: Alcohols & Phenols Review Nomenclature, Structure, Physical Properties, and Acidity on your own,

(pp.564‐574); this material reviews things we have done previously.

1. Preparation of Alcohols

a) Substitution – chapter 7

b) Addition to alkenes – chapter 9

c) Reduction of carbonyls ‐ what is oxidation‐reduction?

2. Preparation of Diols

3. Grignard Reagents

4. Protection of Alcohols

5. Reactions of Alcohols

a) Reaction with HX

b) Reaction with PBr3

c) Reaction with SOCl2/py

d) Reaction with TsCl/py

e) Acid‐catalyzed dehydration (H3PO4 or TsCl/base)

f) Dehydration with POCl3/py

g) Oxidation of alcohols

h) Oxidation of phenols

You should do all the problems in the textbook, but these are some suggested homework problems:

13.30, 13.31, 13.33, 13.35, 13.37‐41, 13.44, 13.47‐49, 13.51, 13.52


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1. Preparation of Alcohols A. Substitution Reactions

B. Addition to Alkenes

C. Reduction of Carbonyls – what is reduction?


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What is oxidation – reduction?

One direction of a reaction will be oxidation and the opposite direction will be reduction:

Oxidation: loss of C—H, the gain of C—Z, or both

Reduction: the gain of C—H, the loss of C—Z, or both


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C. Reduction of Carbonyls (hydride reagents)


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Comparing LAH to NaBH4

• LAH is strong enough to also reduce esters and carboxylic acids, whereas

NaBH4 is generally not.

To reduce an ester, two hydride equivalents are needed. Mechanism?

R OMe

O1. xs LAH

2. H2O


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2. Preparation of Diols

Perform a reduction twice of th reaction we just did!


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3. Grignard Reagents

• 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?

Will it act as an acid, base, electrophile, nucleophile, etc.?

Because the Grignard is both a strong base and a strong nucleophile, care must be taken to protect it from exposure to water.

What solvent is appropriate for these reactions?


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Mechanism?

Ph CH3

OMgCl

1.

2. H2O


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Synthesis: Design a synthesis for the following molecules starting from an alkyl halide and a carbonyl, each having five carbons or less.


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4. Protection of Alcohols

Consider the reaction below. WHY won’t it work?

Strategy for protecting alcohols:


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5. Reactions of Alcohols – how to make a good leaving group?

All of these reactions you will learn in this chapters have one common theme – converting the –OH group into a good, stable leaving group!! a. ROH reaction with HCl, HBr & HI (converting a ROH →RX)

1o ROH react through an SN2 mechanism:


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2o/3o ROH react through an SN1 mechanism:


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b. Reaction with PX3, X = Cl, Br (converting a ROH → RBr)

Reaction Observations:

o This reaction can only be used with 1o and 2o ROH only

o Reaction always occurs with inversion of configuration.

o What substitution mechanism does this support?

Mechanism?


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c. Reaction with Thionyl Halide (SOX2, X = Cl, Br) (converting a ROH → RX)

Reaction Observations:

o This reaction can only be used with 1o and 2o ROH only

o Reaction always occurs with inversion of configuration.

o What substitution mechanism does this support?

Mechanism?

OH

O

SCl Cl


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d. Formation of Tosylates to provide good leaving groups

What is important about this? Sulfonate anions are weak bases, making them VERY GOOD leaving groups. Look at H2SO4 and consider its acidity: Since alcohols make poor leaving groups, reacting them with sulfonyl chlorides converts them into better leaving groups. Most common sulfonyl chloride reagents:

TsCl MsCl (Para‐toluene sulfonyl chloride) (mesyl chloride)


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How do these reactions work overall? It’s a two step reaction, (1) react the desired alcohol with the tosyl chloride without inversion, and (2) react it with the nucleophile leading to inversion of configuration:


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e. Acid‐catalyzed Dehydration of Alcohols to Alkenes (ß‐elimination reaction)

Compare to:

E1 mechanism is observed for 2o and 3o ROHs:

H3PO4, H2O

heat

OH

How do you think the mechanism differs for a 1o ROH?


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Provide the mechanism for the following transformation:


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f. Dehydration of ROH using POCl3 & Pyridine (converting a ROH →alkene)

This mechanism is known to go through an E2 mechanism. Mechanism?


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g. Oxidation of Alcohols (no mechanism to know)

Primary alcohols are oxidized to either aldehydes or carboxylic acids, depending on the reagent employed:

Secondary alcohols are oxidized to ketones.

Tertiary alcohols cannot be oxidized – why?

Common oxidizing reagents are:


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1o ROH give different products depending on the reagent used:

OHPCC

OH

K2Cr2O7

H2SO4, H2O

2o ROH give same products regardless of the reagent used:

OHPCC

K2Cr2O7H2SO4, H2O

or

Provide the organic product for the following reactions. You do not need to balance the byproducts of the reaction.


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h. Oxidation of Phenols

Phenol is even more readily oxidized than primary or secondary alcohols.


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Alcohol Reactions. Provide correct organic product(s) and the mechanism for the following reactions. If stereochemistry pertains, ensure it is clearly demonstrated. If there is more than one product, then circle the major product.

OH

POCl3pyridine

Mechanism?


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OH

Mechanism?

HBr


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Mechanism?

OH

SOCl2pyridine


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Ph H

O 1. LAH

2. H2O


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Provide viable steps to bring about the following transformation.

c341 f2011 chapter 13 alcohols - chemistry courses:...

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