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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4:47 minutes

Problem 59b

Textbook Question

In each part, rank the compounds in order of increasing rate of nucleophilic attack at C=O by a strong nucleophile like methoxide.
(b)

Verified step by step guidance

Step 1: Identify the functional groups attached to the carbonyl (C=O) in each compound. Compound E and F are amides (R-C=O-NH2), compound G is an ester (R-C=O-O-R'), and compound H is an anhydride (R-C=O-O-C=O-R').

Step 2: Understand the electronic effects of the functional groups. Amides (E and F) have resonance stabilization due to the lone pair on nitrogen, which reduces the electrophilicity of the carbonyl carbon. Esters (G) have less resonance stabilization compared to amides, making the carbonyl carbon more electrophilic. Anhydrides (H) are highly reactive due to the presence of two carbonyl groups, which increase the electrophilicity of the carbonyl carbon.

Step 3: Consider steric hindrance. Compound E has bulky alkyl groups near the carbonyl carbon, which can hinder nucleophilic attack. Compound F has less steric hindrance compared to E. Compound G has moderate steric hindrance due to the alkyl group attached to the oxygen. Compound H has minimal steric hindrance.

Step 4: Rank the compounds based on the combined effects of resonance stabilization, steric hindrance, and electrophilicity. Amides (E and F) will have the slowest rate of nucleophilic attack due to resonance stabilization, with E being slower than F due to steric hindrance. Esters (G) will have a faster rate than amides due to reduced resonance stabilization. Anhydrides (H) will have the fastest rate due to high electrophilicity and minimal steric hindrance.

Step 5: Final ranking in order of increasing rate of nucleophilic attack: E < F < G < H.

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Key Concepts

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

Nucleophilicity

Nucleophilicity refers to the ability of a nucleophile to donate an electron pair to an electrophile, such as a carbonyl carbon in a C=O bond. Strong nucleophiles, like methoxide, are more reactive and can effectively attack electrophilic centers. The strength of a nucleophile is influenced by factors such as charge, electronegativity, and steric hindrance.

Electrophilicity of Carbonyl Compounds

The electrophilicity of carbonyl compounds is determined by the nature of the substituents attached to the carbonyl carbon. Electron-withdrawing groups increase the positive character of the carbonyl carbon, making it more susceptible to nucleophilic attack. Conversely, electron-donating groups can decrease electrophilicity, affecting the rate of reaction with nucleophiles.

Steric Hindrance

Steric hindrance refers to the repulsion between atoms that occurs when they are brought close together, which can impede reactions. In the context of nucleophilic attack on carbonyl compounds, bulky substituents around the carbonyl can hinder the approach of nucleophiles, thus affecting the reaction rate. Understanding steric effects is crucial for predicting the reactivity of different carboxylic acid derivatives.

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