1) Write a mechanism with appropriate arrows for the following reactions (You should also indicate any byproducts generated by the mechanism, i.e. SO2, HCl, etc.):

OH

PBr3

Br

O SOCl2

Et3N

Cl

CHEM 343Week of 4/16/2007

a)

b)

P BrBr

Br

O PH

Br

Br

Br

+Br P Br

OH

This can react with two more alcohols by repeating the mechanism.

HO P OH

OH+

Brtwo more of these

TOTAL YIELD: 3 alkyl bromides for every equivalent of PBr3 & one molecule of H3PO3

Cl S Cl

O

H

OH

SCl

Cl

OO

H

SO

Cl+ Cl

O SO

Cl + H Cl

N EtEt

Et N EtEt

Et

H

Cl

Chapter 11, page 506

Chapter 11, page 506

+ O SO

Cl SO2 + Cl

N EtEt

Et

H

(generated below)

CH3CH2O

H2SO4140°C CH2CH3OCH2CH3

Generating ethers via the dehydration of alcohols is limited to the preparation of symmetrical ethers. Draw the products of the following reaction to explain why only symmetrical ethers are prepared this way.

CH3OH + (CH3)2CH2CH2OH

H2SO4140°C

c)

d) OHS Cl

O O

Et3NO

S OO

2)

O OO+ +

This will generate a mixture of these three ethers in roughly equal amounts. When symmetrical ethers are made, there is only one possible ether product.

H

H

O H

H O H

OH

HOR

+ O HR

HR = -CH2CH3, or H-

SCl

O

O

OS OO

ClH

OS O

O

H+

Cl

+

NEt

EtEt

N EtEt

Et

H

Cl

Chapter 11, p 509

Chapter 11, p 511

OImagine that we want to synthesize the ether shown in the box to the right.Suggest a method for preparing this ether using only methanol and isobutyl alcohol as starting materials. (Hint: You will need to activate one of the two alcohols as a good leaving group, using reactions featured in chapter 11.)

Devise a synthetic route to optically active ethers A and B depicted below beginning with the boxed alcohol. Each enantiomer should be accessible in two steps from the alcohol given. Assign absolute stereochemistry to A and B.

(S)(R)

OCH2CH3

A

(R)(R)

OCH2CH3

B

(S)(R)

OH

3)

4)

one enantiomer

OHTsCl, Et3N O S O

O

MeOHNa

(or NaH)MeO Na

MeONa, MeOH

O

-OR-

TsCl, Et3N

Na

(or NaH)

MeOH

OH

OS

OO

O Na

(CH3)2CHCH2ONa,(CH3)2CHCH2OH

O

Note: Use of a tosylate as an alcohol activating group was somewhat arbitrary. You could also activate as a triflate, use PBr3 to activate on alcohol as a bromide, etc. One problem with mesylates, which is outside of the scope of chapter 11 is that mesylates contain acidic protons, so it will participate in acid/base chemistry rather than be displaced by a strongly basic nucleophile.

Also consult p.503-509 for alcohol activation and 512-513 for the Williamson ether synthesis.

1) NaH (strong, non-nucleophilic base to deprotonate)

2) CH3CH2I

1) TsCl, Et3N2) CH3CH2OH, K2CO3

TsCl =S Cl

O

O

S Cl

O

O = TsCl

Notice that over here since we want to avoid elimination, we use K2CO3 and ethanol, instead of alkoxide .

OH

OCH3

OH

OCH3

Beginning with the methylcyclohexene (boxed), indicate the conditions required to obtain each of the products. More than one step may be required. Essentially all routes will prepare racemic mixtures, but pay attention to RELATIVE stereochemistry. (This requires reactions from both chapters 11 and 8!)

OCH3

OHOH

OH

H

OCH2CH3

OCH3

HO

O

O

O

O

1

2

3

4

5

6

7

8

Hg

OCH3

9What is the product of 9 after treatment with NaBH4?

O CF3

O

5)

1) BH3•THF2) H2O2, NaOH

1) peroxy acid2) H+, CH3OH

peroxy acid =R O

OO H

one specific peroxy acid- MMPP (see p 517)

1) peroxy acid2) CH3ONa

1) Hg(O2CF3)2, CH3OH2) NaBH4, NaOH

1) OsO42) NaHSO3, H2O

1) peroxy acid2) H+, CH3OH3) TsCl, Et3N4) CH3CH2OH, K2CO3

KMnO4, H2O,heat

1) O32) Zn, HOAc

Hg(O2CF3)2, CH3OH

OCH3

4