Table of contents

1. A Review of General Chemistry5h 5m
2. Molecular Representations1h 14m
3. Acids and Bases2h 46m
4. Alkanes and Cycloalkanes4h 17m
5. Chirality3h 39m
6. Thermodynamics and Kinetics1h 22m
7. Substitution Reactions1h 48m
8. Elimination Reactions2h 30m
9. Alkenes and Alkynes2h 9m
10. Addition Reactions3h 19m
11. Radical Reactions1h 58m
12. Alcohols, Ethers, Epoxides and Thiols2h 42m
13. Alcohols and Carbonyl Compounds2h 17m
14. Synthetic Techniques1h 26m
15. Analytical Techniques:IR, NMR, Mass Spect7h 3m
16. Conjugated Systems6h 13m
17. Ultraviolet Spectroscopy51m
18. Aromaticity2h 34m
19. Reactions of Aromatics: EAS and Beyond5h 1m
20. Phenols55m
21. Aldehydes and Ketones: Nucleophilic Addition4h 56m
22. Carboxylic Acid Derivatives: NAS2h 51m
23. The Chemistry of Thioesters, Phophate Ester and Phosphate Anhydrides1h 10m
24. Enolate Chemistry: Reactions at the Alpha-Carbon1h 53m
25. Condensation Chemistry2h 9m
26. Amines1h 43m
27. Heterocycles2h 0m
28. Carbohydrates5h 53m
29. Amino Acids4h 20m
30. Peptides and Proteins2h 42m
31. Catalysis in Organic Reactions1h 30m
32. Lipids 2h 50m
33. The Organic Chemistry of Metabolic Pathways2h 52m
34. Nucleic Acids1h 32m
35. Transition Metals6h 14m
36. Synthetic Polymers1h 49m

22. Carboxylic Acid Derivatives: NAS

Nucleophilic Acyl Substitution

Organic Chemistry

22. Carboxylic Acid Derivatives: NAS

Nucleophilic Acyl Substitution

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6:45 minutes

Problem 32c,d

Textbook Question

Show how you would use anhydrides to synthesize the following compounds. In each case, explain why an anhydride might be preferable to an acid chloride.
(c) phthalic acid monoamide
(d) succinic acid monomethyl ester

Verified step by step guidance

Step 1: Understand the reactivity of anhydrides compared to acid chlorides. Anhydrides are less reactive than acid chlorides, making them easier to control in reactions. They also avoid the generation of HCl as a byproduct, which can be corrosive and require neutralization.

Step 2: For (c) phthalic acid monoamide, start with phthalic anhydride. React phthalic anhydride with one equivalent of ammonia (NH₃). The nucleophilic attack of ammonia on one of the carbonyl groups of the anhydride will result in the formation of phthalic acid monoamide and a carboxylic acid group.

Step 3: For (d) succinic acid monomethyl ester, begin with succinic anhydride. React succinic anhydride with one equivalent of methanol (CH₃OH). Methanol will act as a nucleophile, attacking one of the carbonyl groups of the anhydride to form the monomethyl ester and a carboxylic acid group.

Step 4: Explain why anhydrides are preferable to acid chlorides in these syntheses. Acid chlorides are highly reactive and can lead to overreaction or side products. Anhydrides provide better control over the reaction, especially when forming mono-substituted products like monoamides or monomethyl esters.

Step 5: Highlight the importance of stoichiometry in these reactions. Using one equivalent of the nucleophile (ammonia or methanol) ensures that only one carbonyl group of the anhydride reacts, leaving the other as a carboxylic acid group in the final product.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Anhydrides in Organic Synthesis

Anhydrides are reactive compounds derived from acids by the removal of water. They are commonly used in organic synthesis due to their ability to acylate nucleophiles, forming new carbon-carbon or carbon-heteroatom bonds. Their reactivity allows for the formation of various functional groups, making them versatile intermediates in the synthesis of complex molecules.

Comparison with Acid Chlorides

Acid chlorides are another class of reactive acylating agents, but they can be more reactive and less selective than anhydrides. While both can be used to synthesize amides and esters, anhydrides are often preferred for their milder reactivity, which can lead to fewer side reactions and better yields in certain reactions, especially when sensitive functional groups are present.

Synthesis of Phthalic Acid Monoamide and Succinic Acid Monomethyl Ester

The synthesis of phthalic acid monoamide and succinic acid monomethyl ester using anhydrides involves nucleophilic attack by amines and alcohols, respectively, on the anhydride. This process allows for the selective formation of the desired products while minimizing by-products. Understanding the specific reactivity of anhydrides in these reactions is crucial for optimizing yields and ensuring the correct functionalization of the target compounds.

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