Chem320 – Chapter 30 - Clayden

1. Explain what the equation below means? (2)

2. Provide a retrosynthetic reaction the compound below, where the C-O ester bond is formed.
(2)

3. Provide a retrosynthetic reaction the compound below, where the amide bond is formed.
(2)

4. Suggest a retrosynthetic reaction between a cyclic compound and an amine to form the
compound below. (3)

5. Provide a retrosynthetic reaction for the compound below using synthons, rather than
reagents (for the disconnection suggested below). (2)

6. Provide suitable reagents to replace the corresponding synthons in the question above. (2)
7. Provide the normal reaction (and conditions) to synthesise the target above using the
reagents suggested. (2)
8. Define the following terms: (6)

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9. It is important to choose a good disconnection position when doing retrosynthesis. Below is
a proposed disconnection with the resulting synthons. Convert the synthons to suitable
reagents and discuss the merit of the proposed retrosynthesis. (4)

10. Provide suitable reagents and reaction conditions for the synthons below. (3)

11. Provide suitable reagents for the disconnection reaction below. (2)

12. Use the starting material below and propose a suitable synthesis for the target molecule
above. (4)

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13. Provide suiable synthons for each of the disconnections suggested below: (8)

14. The disconnection (b) will result in 4-chloro-pyridine as reagent. The proposed synthesis is
not going to work well, as demonstrated below:

For disconnection (a) the following side reaction will occur:

O O
O
HN N
Cl N +

NH2 N
NH2
O
And for disconnection (b) the following side reaction will occur:
Cl

O O O

Cl N
N Cl
+
NH2 NH N
O

N
The problem can be overcome by a Functional Group Interconversion (FGI). Propose a FGI for the
starting material below, to overcome this problem. Complete the rest of the synthesis in order to
show how you would obtain the target material. (6)

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15. Below is a proposed retrosynthesis strategy. Discuss the feasibility of the strategy by
providing the actual proposed synthesis and indicating any side reactions. (4)

(Hint: a secondary amine is a stronger nucleophile than a primary amine; a tertiary amine is a
stronger nucleophile than a secondary amine).
16. Provide an alternative retrosynthesis for the synthesis of the secondary amine, which is not
prone to side reactions. (3)
17. There is a second alternative retrosynthetic strategy to obtain the same target material.
Provide that as well. (3)
18. The second reaction is not readily taken place. Explain what is the most likely reason for
that? (1)

19. An electronic reason may also be used to explain why the aromatic secondary amine is not
such a strong nucleophile? Explain this statement (provide relevant structures if required).
(2)
20. Provide a suitable FGI retrosynthesis for the target material below.

(3)

(3)

(3)

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21. Discuss the feasibility of the two disconnection reactions proposed below? (3)

22. Two group disconnections are very convenient. Propose a two group disconnection reagent
for the synthon below (1,2 disconnection). (2)

23. Propranolol is one of the top heart drugs currently used (β-blocker). Propose a retroynthesis
strategy for the drug, starting from 1-hydroxynaphthalene and making use of a 1,2-
disconnection. (5)

Propranolol 1-hydroxynaphthalene

24. Suggest (a) synthons for the disconnection below and then reagents for each synthon:

(4)

(4)

(4)
5
 (4)

(4)

(4)

(4)

(4)

(4)

(4)

6
 (4)

(4)

(4)

(4)

(4)

(4)

7
 (4)

(4)

(6)

(4)

(4)

(4)

(4)

8
 (4)

(4)

(4)

25. Suggest a retrosynthesis strategy for the target below, starting from an appropriate alkyne.

(5)

26. Suggest a retrosynthesis strategy for the target below, using acetylene (HC≡CH) and an
appropriate alcohol as starting materials. (7)

O
Target reagent to protect an alcohol

27. Suggest a retrosynthesis strategy for the target below. (5)

28. Provide the corresponding synthesis of the target material above. (5)
29. Suggest a retrosynthesis strategy for the target below. (5)

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 TM SM

30. Suggest a retrosynthesis strategy for the target below. (5)

TM SM

31. Provide the corresponding synthesis of the target material above. (5)
32. Provide the corresponding reagents for the synthons below: (4)

33. Suggest a retrosynthesis strategy for the target below. (5)

TM SM
34. Suggest a retrosynthesis strategy for the target below. (5)

TM SM
35. Provide the resulting reagent for the FGI below. (1)

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