Chapter 10 Outline: Alcohols - Indiana University...

C341/Spring 2010 Chapter 10

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Chapter 10 Outline: Alcohols Review Nomenclature, Structure & Physical Properties on your own

1. Acidity of Alcohols

2. Reactions of Alcohols

3. Reactions of Thiols

You should do all the problems in the textbook, but these are some suggested homework problems: 10.15, 10.16, 10.18, 10.20, 10.21, 10.26 – 10.31, 10.35, 10.35 – 10.40, 10.42, 10.43, 10.45, 10-51 – 10.54.


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Roadmap for chapter 10:


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1. Acidity of Alcohols Alcohols have pKas in the range of 16-18. Only methanol has an acidity less than water (pKa 15.5 and will protonate water preferentially). In general, all alcohols will be less polar and less acidic than water. What happens when water is in solution with ethanol (pKa = 15.9)?

Reaction of an alcohol with strong base, like sodium hydride, or Group I metals (Li, Na, K): • CH3OH + NaH → CH3ONa + H2

sodium methoxide

• 2 CH3OH + 2 Na → 2 CH3ONa + H2


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2. 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!! What if we protonate the –OH group? Does that become a better leaving group? A strong, non-halide containing acid like H3PO4 or H2SO4 or TsOH is used to protonate an alcohol.

= TsOH SO3H

p‐toluene sulfonic acid


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a. ROH reaction with HCl, HBr & HI (converting a ROH →RX)

1o ROH react through an SN2 mechanism:

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?


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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:

O

S Cl

O

H3C

O

SH3C Cl

O 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 (β-elimination reaction) Compare to:

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

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. Pinnacol Rearragenment


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h. 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

OHK2Cr2O7

H2SO4, H2O 2o ROH give same products regardless of the reagent used:

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


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i. Reaction of glycols with periodic acid


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3. Reactions of Thiols

L-Cysteine =


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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.

H3PO4, heat

OH

Mechanism?

OHPOCl3

pyridine

Mechanism?


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Mechanism?

OH

PBr3

OH

Mechanism?

HBr


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Mechanism?

OH

SOCl2pyridine

OH

Mechanism?

1. TsCl, pyridine

2.O

ONa

OH

1. NaH

2. CH3CH2Br

Mechanism?


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Provide viable steps to bring about the following transformation.

Chapter 10 Outline: Alcohols - Indiana University...

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