1. 17.4 How Aldehydes and Ketones React (Part III)
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17.4 How Aldehydes and Ketones React (Part III)
Electron rich (Lewis base, Nu) d- d+
Electron deficient (Lewis acid, E+)
R = alkyl or aryl (C)
Y = alkyl, aryl or H (class II) (No leaving group)

2. Nucleophilic Addition (Class II)
1. General mechanism in basic condition:
2. General mechanism in acidic condition:

3. Important pKa to Remember
Names
Acids
H-Z
Approx. pKa
Conjugate Base, :Z
General Roles of :Z
Alkane (2°) 51
Base as Li+ salt
Nucleophile as Grignard reagent
Amine 38
Base and Nucleophile
Hydrogen 35
Base in NaH, CaH2
Nucleophile in LiAlH4, NaBH4
Alcohol water
15-16
Often as a base but can be a nucleophile
Ammonium
10-11
Weak base, but can be a nucleophile
Thiol
Nucleophile
Carboxylic Acid
4-5
Weak base, poor leaving group
Hydrochloric Acid -7
Leaving group, poor nucleophile

4. Types of Nucleophile for Class II Carbonyl Groups
1. Carbon as the nucleophilic atom
Basic condition
pKa = 25
Acetylide ion
pKa = 50
carboanion
2. Hydrogen as the nucleophilic atom
hydride
Mostly basic condition
3. Nitrogen as the nucleophilic atom
1° and 2° amines
Mostly acidic condition
4. Oxygen as the nucleophilic atom
Acidic condition
1° alcohols

5. Oxygen as the Nucleophilic Atom
pKa of alcohol.
pKa = 15-16
pKa = -2
1° and 2° Alcohols function as weak acids, weak bases or nucleophiles.
3° Alcohols function as weak acids or weak bases.

6. Reactions of Aldehydes and Ketones with Alcohols
2° and 3° Alcohols are too hindered to react.
General reaction with primary alcohols: H+ 2
1° Alcohols
Ketal or acetal
General reaction with water: H+
Geminal diol (gem-diol)

7. Reactions of Aldehydes and Ketones with Water
Example: H+
Mechanism:

8. Reactions of Aldehydes and Ketones with Alcohols
Examples: H+ 2 H+ 2 H+ 1

9. Reactions of Aldehydes and Ketones with Alcohols
Mechanism:
hemiacetal
acetal

10. Application of Ketal or Acetal
Synthesis using protecting group ?
LiAlH4 or DIBAL will reduce the ketone as well.
Ketal as the protecting group for ketone:
Ketals like ethers are relatively stable in basic condition.

11. Mechanism for the Formation of Cyclic Ketal

12. More Examples on the Use of Protecting Groups?
SOCl2 (PBr3 or PCl3) will convert carboxylic acids into acyl halides as well.
Ester as the protecting group for carboxylic acid:
Ester will not react with SOCl2 (from compound 3 to compound 4).

13. More Examples on the Use of Protecting Groups
Amines under acidic condition may turn into an EWG in the form of ammoniim ions.
Amide as the protecting group for amine:
Amide in compound 3 will act as EGD..

14. Formation of Cyclic Hemiacetals or Ketals
Intramolecular reaction: formation of 5 or 6-membered rings

15. Cyclic Hemiacetals in Carbohydrates
Intramolecular formation of 5 or 6-membered rings
D-Glucose

16. Learning Check
1. What could be the reagent and reaction condition for the following transformation?
(a) ethanol, NaOH
(b) ethanol, H+
(c) methanol, NaOH
(d) methanol, H+
(e) None of the above
2. What should be the product from the following reaction?

17. Learning Check
3. What could be the product for the following reaction?

18. Learning Check
4. Which hydroxy group when added to the aldehyde functional group (C-1) of open chain glucose will produce the cyclic hemiacetal form shown below?
(a) The one that locates on C-2.
(b) The one that locates on C-3.
(c) The one that locates on C-4.
(d) The one that locates on C-5.
(e) None of the above

19. Learning Check
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5. Which hydroxy group when added to the aldehyde functional group (C-1) of open chain glucose will produce the cyclic hemiacetal form shown below?
(a) The one that locates on C-2.
(b) The one that locates on C-3.
(c) The one that locates on C-4.
(d) The one that locates on C-5.
(e) None of the above