Chapter 19

Question 1

Show the products you would obtain by acid-catalyzed reaction of 3-pentanone with
methylamine, CH₃NH₂, and with dimethylamine, (CH₃)₂NH.

Answer 1

Question 2

Wolff-Kishner Reaction

Answer 2

• treatment of aldehyde or ketone with hydrazine: H₂NNH₂ in the precense of KOH
• useful and general method for converting an aldehyde or ketone into an alkane

Question 3

What are the products of the following Wolff-Kischner reactions?

Answer 3

Question 4

What is the mechanism for Enamine Formation?

Answer 4

1. Nucleophilic addition of a secondary amine to the ketone or aldehyde, followed by proton transfer from nitrogen to oxygen, yields an intermediate carbinolamine in the normal way.
2. Protonation of the hydroxyl by acid catalyst converts it into a better leaving group.
3. Elimination of water by the lone-pair electrons on nitrogen then yields an intermediate iminium ion.
4. Loss of a proton from the alpha carbon atom yields the enamine product and regenerates the acid catalyst.

Question 5

What is the mechanism for Imine Formation?

Answer 5

1. Nucleophilic attack on the ketone or aldehyde by the lone-pair electrons of an amine leads to a dipolar tetrahedral intermediate.
2. A proton is then transferred from nitrogen to oxygen, yielding a neutral carbinolamine.
3. Acid catalyst protonates the hydroxyl oxygen.
4. The nitrogen lone-pair electrons expel water, giving an iminium ion.
5. Loss of H+ from nitrogen then gives the neutral imine product.

Question 6

Draw the mechanism for the Wolff-Kischner Reaction Starting with CORR’.

Answer 6

1. Reaction of the aldehyde or ketone with hydrazine yields a hydrazone in the normal way.
2. Base abstracts a weakly acidic N–H proton, yielding a hydrazone anion.
3. This anion has a resonance form that places the negative charge on carbon and the double bond between nitrogens.
4. Protonation of the hydrazone anion takes place on carbon to yield a neutral intermediate.
5. Deprotonation of the remaining weakly acidic N–H occurs with simultaneous loss of nitrogen to give a carbanion . . .
6. . . . which is protonated to give the alkane product.

Question 7

Draw the Mechanism of acid-catalyzed acetal
formation by reaction of an aldehyde or
ketone with an alcohol.

Answer 7

1. Protonation of the carbonyl oxygen strongly polarizes the carbonyl group and . . .
2. . . . activates the carbonyl group for nucleophilic attack by oxygen lone-pair electrons from the alcohol.
3. Loss of a proton yields a neutral hemiacetal tetrahedral intermediate.
4. Protonation of the hemiacetal hydroxyl converts it into a good leaving group.
5. Dehydration yields an intermediate oxonium ion.
6. Addition of a second equivalent of alcohol gives a protonated acetal.
7. Loss of a proton yiields the neutral acetal product.

Question 8

19.58) Tamoxifen is a drug used in the treatment of breast cancer.

How would you prepare tamoxifen from benzene, the following ketone, and any other reagents needed?

Answer 8

NOTE: Whittig rxn does not work here bc of steric hindrance. Coupling step achieved via Grignard reaction btwn ketone and Grig reagent followed by dehydration.

Question 9

19.40 Carvone is the major constituent of spearmint oil. What products would you expect from reaction of carvone with the following reagents?

Answer 9

Question 10

Wittig Example

Answer 10

Question 11

HemiKetal

Answer 11

• CH₃C(OH)(OR)CH₃
  *

Question 12

Ketal

Answer 12

CH₃C(OH)₂CH₃