21: Carboxylic Acid Derivatives- Nucleophilic Acyl Substitution Reactions
- Page ID
- 448777
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)The compounds discussed in this chapter are all considered to be derived from carboxylic acids, and include acid halides, acid anhydrides, esters and amides (thioesters and acyl phosphates are also briefly mentioned). As you proceed through the chapter, you should be looking for similarities in behaviour among the various classes of compounds. These similarities can be readily understood once you appreciate the fact that, in most of their reactions, carboxylic acid derivatives react via the nucleophilic acyl substitution mechanism.
In this chapter, we describe the nomenclature of the various types of carboxylic acid derivatives, and explain the relative reactivity of these compounds in terms of resonance contributions to the ground state of each type of compound.
We describe the reactions of carboxylic acids, acid halides, acid anhydrides, esters, amides, polyamides and polyesters in detail, and discuss the biological importance of thiol esters briefly. The chapter concludes with a look at how infrared spectroscopy and NMR spectroscopy can be used in the identification of unknown carboxylic acid derivatives.
- 21.0: Why This Chapter?
- Carboxylic acid derivatives are among the most widely occurring of all molecules, both in laboratory chemistry and in biological pathways. Thus, a study of them and their primary reaction—nucleophilic acyl substitution—is fundamental to understanding organic chemistry. We’ll begin this chapter by first learning about carboxylic acid derivatives, and we’ll then explore the chemistry of acyl substitution reactions.
- 21.1: Naming Carboxylic Acid Derivatives
- This page discusses the naming conventions for carboxylic acid derivatives, emphasizing the importance of identifying functional groups and their hierarchy in nomenclature. Derivatives such as esters, amides, and anhydrides are named based on their structure, with specific suffixes and prefixes used to indicate their relationships to carboxylic acids.
- 21.2: Nucleophilic Acyl Substitution Reactions
- This page explores nucleophilic acyl substitution reactions, a key process in organic chemistry where a nucleophile attacks a carbonyl carbon of a carboxylic acid derivative. The mechanism involves the formation of a tetrahedral intermediate, followed by the departure of a leaving group. The discussion includes examples with various derivatives like esters and amides, highlighting factors that influence reaction rates and outcomes.
- 21.3: Reactions of Carboxylic Acids
- This page discusses the reactions of carboxylic acids, focusing on their behavior in nucleophilic acyl substitution reactions. It covers the reactivity of carboxylic acids, their derivatives, and the conditions that influence these reactions. Key reactions include esterification, acid chloride formation, and the hydrolysis of esters. The significance of the functional groups present and their impact on reactivity is also highlighted. Understanding these reactions is crucial for organic synthesis
- 21.4: Chemistry of Acid Halides
- The page on the chemistry of acid halides explains how carboxylic acid derivatives, specifically acid halides, are formed and their reactivity. It covers the preparation of acid halides through reactions with thionyl chloride or phosphorus tribromide, as well as their high reactivity due to the polar nature of the carbon-halogen bond. Acid halides undergo nucleophilic acyl substitution reactions with alcohols, amines, and water, making them useful intermediates in organic synthesis.
- 21.5: Chemistry of Acid Anhydrides
- The page on acid anhydrides explains how they are carboxylic acid derivatives formed by the dehydration of two carboxylic acid molecules. Acid anhydrides are reactive compounds used in acylation reactions, which involve nucleophilic acyl substitution. The page details their preparation, reactions with alcohols, water, and amines, and how they are commonly employed in synthetic chemistry, especially in producing esters, amides, and carboxylic acids.
- 21.6: Chemistry of Esters
- Lactam antibiotics, particularly β-lactams like penicillin and cephalosporins, are critical for inhibiting bacterial cell wall synthesis. They work by targeting peptidoglycan in bacteria. This class of antibiotics is widely used to treat bacterial infections, though resistance through β-lactamase enzymes poses a significant challenge. Modified versions, such as methicillin, help overcome resistance. These antibiotics play a vital role in modern medicine.
- 21.7: Chemistry of Amides
- Amides are carboxylic acid derivatives with an -NH₂, -NHR, or -NR₂ group replacing the hydroxyl group of a carboxylic acid. They are classified as primary, secondary, or tertiary based on the number of substituents on nitrogen. Amides are notable for their resonance stabilization, making them less reactive than esters or anhydrides. Hydrolysis of amides, catalyzed by acids or bases, produces carboxylic acids and amines. Amides are important in pharmaceuticals and polymers like nylon.
- 21.8: Chemistry of Thioesters and Acyl Phosphates - Biological Carboxylic Acid Derivatives
- Thioesters and acyl phosphates are biologically significant carboxylic acid derivatives. Like acetyl-CoA, they play a critical role in metabolism due to their high reactivity. Acyl phosphates are key intermediates in biochemical reactions, including energy transfer and activation of substrates. Both thioesters and acyl phosphates undergo nucleophilic acyl substitution reactions similar to other carboxylic acid derivatives but are more reactive due to weaker bonds with sulfur or phosphate groups.
- 21.9: Polyamides and Polyesters - Step-Growth Polymers
- This section discusses polyamides and polyesters, focusing on their formation through step-growth polymerization. Polyamides, such as nylon, form via the reaction of diamines with dicarboxylic acids, while polyesters, like PET, result from the reaction of diols with dicarboxylic acids. The text explains the process of polymerization, the role of condensation reactions, and highlights the applications and properties of these polymers, including their importance in everyday materials.
- 21.10: Spectroscopy of Carboxylic Acid Derivatives
- This section covers the spectroscopy of carboxylic acid derivatives, including techniques such as infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS). These methods are can be used to identify functional groups, structural features, and specific chemical environments in carboxylic acid derivatives, such as esters, amides, and anhydrides. Details are discussed on characteristic spectral data, focusing on the analysis of bond vibrations and electron environments.
- 21.11: Chemistry Matters—β-Lactam Antibiotics
- Lactam antibiotics are essential in modern medicine. Lactams, particularly β-lactams like penicillin and cephalosporins, inhibit bacterial cell wall synthesis by targeting peptidoglycan. The section highlights their chemical structure, mode of action, and significance in combating bacterial infections. Resistance, often caused by β-lactamase enzymes, poses challenges, but modified versions like methicillin address this issue.
- 21.13: Summary
- This section provides a summary of the reactions and properties of carboxylic acid derivatives. It highlights key nucleophilic acyl substitution mechanisms and their applications in organic chemistry, comparing the behavior of various derivatives such as esters, amides, and anhydrides.The reactivity and stability differences among these compounds are discussed. This chapter serves as a review of the core concepts related to the chemistry of carboxylic acid derivatives.
- 21.14: Summary of Reactions
- The "Summary of Reactions" section discusses nucleophilic acyl substitution reactions involving carboxylic acid derivatives. It highlights the mechanisms by which various derivatives, such as esters, amides, and anhydrides, react with nucleophiles. Key reactions include the conversion of these derivatives into one another through substitution processes. The summary provides a concise overview of the reactivity and transformations of carboxylic acid derivatives.