1. 17.8 Acetal Formation 1

2. Compounds related to imines The Wittig reaction
Some reactions of aldehydes and ketones progress beyond the nucleophilic addition stage
Acetal formation
Imine formation
Enamine formation
Compounds related to imines
The Wittig reaction 22

3. Recall Hydration of Aldehydes and Ketones
HOH C •• O
• • HO H R R' 5

4. Alcohols Under Analogous Reaction with Aldehydes and Ketones
R"OH C •• O
• • R R'
R"O H
Product is called a hemiacetal. 5

5. Hemiacetal reacts further in acid to yield an acetal
R"O C O H •• R R'
Product is called an acetal.
ROH, H+
R"O C O H •• R R'
Product is called a hemiacetal. 5

6. Benzaldehyde diethyl acetal (66%)
Example CH O +
2CH3CH2OH
HCl
CH(OCH2CH3)2
+ H2O
Benzaldehyde diethyl acetal (66%) 6

7. Diols Form Cyclic Acetals
CH3(CH2)5CH +
HOCH2CH2OH
benzene
p-toluenesulfonic acid H
(CH2)5CH3
H2C
CH2 O C +
H2O
(81%) 7

8. Important exception: Cyclic acetals can be prepared from ketones.
In general:
Position of equilibrium is usually unfavorable for acetal formation from ketones.
Important exception: Cyclic acetals can be prepared from ketones. 8

9. Example O C6H5CH2CCH3 + HOCH2CH2OH H2C CH2 O O + H2O (78%) C C6H5CH2
benzene
p-toluenesulfonic acid
H2C
CH2 O O +
H2O
(78%) C
C6H5CH2
CH3 7

10. Mechanism of Acetal Formation
First stage is analogous to hydration and leads to hemiacetal
acid-catalyzed nucleophilic addition of alcohol to C=O 10

11. Mechanism H R + O
• • R H O
• • C O ••
• • 10

12. Mechanism H R H O
• • •• + C O O
• •
• • H R 10

13. Mechanism R H O
• • •• + C O H 10

14. Mechanism R •• •• O C O
• • + H H 10

15. Mechanism C O ••
• • H + R O R H •• 10

16. Mechanism C O ••
• • H R H + O •• R H 10

17. Mechanism of Acetal Formation
Second stage is hemiacetal-to-acetal conversion
involves carbocation chemistry 15

18. Hemiacetal-to-acetal StageR + O
• • C O ••
• • H R 16

19. Hemiacetal-to-acetal StageR O
• • R H •• •• O + C O •• H 16

20. Hemiacetal-to-acetal StageR H •• •• O + C O •• H 16

21. Hemiacetal-to-acetal StageR O •• H
• • •• O C + •• 16

22. Hemiacetal-to-acetal Stage•• R + R + O C ••
Carbocation is stabilized by delocalization of unshared electron pair of oxygen 16

23. Hemiacetal-to-acetal Stage•• R + O •• H R
• • 16

24. Hemiacetal-to-acetal Stage•• R + H 16

25. Hemiacetal-to-acetal Stage•• R + H O •• H R
• • 16

26. Hemiacetal-to-acetal Stage•• R R •• H O + H 16

27. reverse of acetal formation; hemiacetal is intermediate
Hydrolysis of Acetals
OR" R R' C
+ H2O C R R' O
2R"OH +
mechanism:
reverse of acetal formation; hemiacetal is intermediate
application:
aldehydes and ketones can be "protected" as acetals. 26

28. 17.9 Acetals as Protecting Groups28

29. The conversion shown cannot be carried out directly...
Example
The conversion shown cannot be carried out directly... CH
CH3CCH2CH2C O
1. NaNH2 2. CH3I
CCH3
CH3CCH2CH2C O 29

30. because the carbonyl group and the carbanion are incompatible functional groups.
CH3CCH2CH2C O – 31

31. Strategy
1) protect C=O
2) alkylate
3) restore C=O 32

32. Example: Protect O + CH3CCH2CH2C CH HOCH2CH2OH H2C CH2 O C CH2CH2C CH
benzene
p-toluenesulfonic acid
H2C
CH2 O C
CH3
CH2CH2C CH 7

33. Example: Alkylate H2C CH2 O C CH2CH2C CCH3 CH3 H2C CH2
1. NaNH2 2. CH3I
CH2CH2C CH 7

34. Example: Deprotect H2C CH2 O C CH3 CH2CH2C CCH3 H2O HCl CCH3
CH3CCH2CH2C O +
HOCH2CH2OH
(96%) 7