Jumat, 09 Oktober 2009

Carboxylic Acids I

Introduction

The carboxylic acid family consists of those molecules which contain the core structure outlined in Figure 1.

Figure 1

The Heart of the Carboxylic Acid Family

The core structure shown in red in Figure 1 is called the acyl group. It is similar to the carbonyl group in aldehydes and ketones, but differs from a carbonyl group in that the atom X has at least one lone pair of electrons. The interaction of this electron pair with the pi system of the carbonyl group is responsible for some significant differences between the chemical reactivity of aldehydes and ketones on the one hand and members of the carboxylic acid famiily on the other.

Table 1 summarizes the family relationships implied in Figure 1.

Table 1

It's All in the Family

X
Name
Structure
O-H
carboxylic acid
O-R
carboxylic ester
anhydride
NR2
amide
halogen
carboxylic acid halide (acyl halide)

Figure 2 shows representative examples of all members of the carboxylic acid family.

Figure 2

Examples of Carboxylic Acids and Related Compounds

An interactive model of acetic acid will give you a better feel for the structure of this type of compound.

Many carboxylic acids and their derivatives are important biomolecules.

This topic examines the properties, preparation and reactions of carboxylic acids. The chemistry of the remaining members of the carboxylic acid family is discussed in the following topic.

Acidity of Carboxylic Acids

In terms of organic molecules, carboxylic acids are considered strong acids. Generally the pKa of carboxylic acids is approximately 5. In comparison, the pKa of alpha hydrogens of aldehydes and ketones is approximately 19. Figure 3 compares the reactions of formic acid and acetaldehyde with hydroxide ion.

Figure 3

Acid-Base Comparison of Acetaldehyde and Formic Acid

The equilibrium constant for the reaction of formic acid with hydroxide ion is approximately 1011, while that for acetaldehyde is about 10-3.


Exercise 1 The difference in pKa values of the OH and CH protons in formic acid and acetaldehyde is 14 powers of 10. The difference in pKa values of the OH and CH protons in water and methane is 34 powers of 10. How do you rationalize this data?

Exercise 2 Sodium benzoate is commonly used as a preservative in carbonated beverages. Write an equation describing the preparation of sodium benzoate from benzoic acid.


Preparation of Carboxylic Acids-

Oxidation of Primary Alcohols

Primary alcohols are easily oxidized by chromic acid to produce carboxylic acids. Equation 1 offers a simple example.

The reaction shown in Equation 1 is used by law enforcement agencies to test for OUI violations. During a "Breathalyzer" test, the person suspected of operating under the influence of alcohol exhales into a tube leading into a solution of potassium dichromate in sulfuric acid. The chromic acid oxidizes any alcohol to acetic acid. Oxidation of the alcohol is accompanied by reduction of the chromium from the +6 to the +3 oxidation level, a change that is accompanied by a change in color; Cr6+ is reddish-orange, while Cr3+ is blue-green. The greater the alcohol concentration in the suspect's breath, the greater the color change, which is measured quantitively with a small spectrophotometer that is part of the "Breathalyzer" apparatus.


Exercise 3 What is the oxidation level of the methylene carbon in ethanol? What is the oxidation level of the acyl carbon in acetic acid?


In terms of synthetic chemistry, it is important to relate the type of transformation shown in Equation 1 to the reactions that are used for the preparation of alcohols, e.g. hydration of alkenes and formation of aldehydes via aldol reactions. Equations 2 and 3 provide examples of reaction sequences that involve both of these methods.

In this reaction the hydroboration/oxidation sequence leads to the addition of the "elements of" water to the double bond of a-methylstyrene in an anti-Markovnikov fashion. Oxidation of the resulting primary alcohol yields 2-phenylpropanoic acid.


Exercise 4 What is the oxidation level of the terminal carbon in a-metylstyrene ? What is the oxidation level of the acyl carbon in 2-phenylpropanoic acid?

The reaction sequence illustrated by Equation 3 begins with an aldol condensation that produces the a,b-unsaturated aldehyde 2-butenal. Oxidation of the aldehyde group to a carboxylic acid is straightforward.

Carbonation of Organometallic Reagents

In the same way that they react with aldehydes and ketones to produce alcohols, organometallic reagents react with carbon dioxide to form carboxylic acids. Figure 4 illustrates this method for the preparation of benzoic acid.

Figure 4

Preparation of Benzoic Acid


Exercise 5 Draw the structure of the carboxylic acid that would be formed in each of the following transformations.


Hydrolysis of Nitriles

Nitriles are related to carboxylic acids. Specifically, they may be converted into carboxylic acids by hydrolysis with aqueous acid or base. Equation 4 describes the tranformation in general terms. Nitriles, RCN, may be prepared by the Sn2 reaction of primary and secondary alkyl halides with cyanide ion.

Figure 5 illustrates the hydrolysis of a nitrile as the final step in the Strecker synthesis of alanine, an a-amino acid.

Figure 5

The Strecker Synthesis of Alanine


Exerise 6 Draw the structure of the product as well as any labeled intermediate structures in each of the following reactions.


The Iodoform Reaction

Methyl ketones react with a basic solution of diiodine to form carboxylic acids that contain one fewer carbon atoms. Equation 5 illustrates this transformation in general terms.

The reaction is called the iodoform reaction because the methyl group is converted into iodoform, CHI3, which precipitates from the solution as a bright yellow solid. While the iodoform test is most commonly used as a qualitative test for methyl ketones, it is occassionally used as a synthetic reaction.


Exercise 7 Draw the structure of the carboxylic acid that is formed in each of the following reactions.


Reactions of Carboxylic Acids

Preparation of Acid Chlorides

Carboxylic acids react with chlorinating agents such as thionyl chloride, SOCl2, and phosphorous trichloride, PCl3, to produce the corresponding acid chloride. Thionyl chloride and phosphorous trichloride are electrophilic reagents. (Why?) Figure 6 outlines a mechanism that rationalizes the formation of acetyl chloride from the reaction of acetic acid with thionyl chloride.

Figure 6

Formation of an Acid Chloride

Carboxylic acid chlorides are very reactive compounds. As such they are not generally synthetic targets, but rather intermediates which are useful in the synthesis of other carboxylic acid derivatives such as esters and amides. Experimentally the preparation of acid chlorides is accomplished by refluxing the carboxylic acid in an excess of thionyl chloride. After the reaction is complete, the excess thionyl chloride is distilled and the acid chloride is used directly to prepare the desired ester or amide.

Esterification

Carboxylic acids react with alcohols in the presence of an acid catalyst to produce esters. The reaction is called Fischer esterification. Equation 6 illustrates the application of this reaction for the preparation of methyl salicylate, a component of oil of wintergreen.

Isotopic labeling experiments reveal that the oxygen atom originally present in the methanol ends up in the ester as shown in Equation 7.

This result shows clearly that the methanol acts as a nucleophile in this reaction, with the (protonated) OH group serving as a leaving group. We will discuss the mechanistic details of this result in the following topic.

Anhydride Formation

Treatment of a carboxylic acid with a strong acid such as H2SO4 in the absence of a nucleophile such as methanol leads to the formation of carboxylic acid anhydrides. Like acid chlorides, acid anhydrides are generally not target molecules, but rather they are used as intermediates in the synthesis of other members of the carboxylic acid family such as esters and amides. Equation 8 outlines the preparation of acetic anhydride from acetic acid.


Exercise 8 Draw the structure of benzoic anhydride.

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