Carboxylic Acids & Their Derivatives. Organic Chemistry, 2nd Edition David R. Klein

Transcription

1 Carboxylic Acids & Their Derivatives Organic Chemistry, 2nd Edition David R. Klein

2 Introduction to Carboxylic Acids Carboxylic acids are compounds with a -COOH group. These compounds are abundant in nature, where they are responsible for some familiar odors. Carboxylic acids are also found in a wide range of pharmaceuticals that are used to treat a variety of conditions.

3 Nomenclature of Carboxylic Acids Monocarboxylic Acids Monocarboxylic acids, compounds containing one carboxylic acid group, are named with the suffix oic acid : The parent is the longest chain that includes the carbon atom of the carboxylic acid group. That carbon atom is always assigned number 1 when numbering the parent. When a carboxylic acid group is connected to a ring, the compound is named as an alkane carboxylic acid; for example:

4 Many simple carboxylic acids have common names accepted by IUPAC. Diacids Diacids, compounds containing two carboxylic acid groups, are named with the suffix dioic acid ; for example: Many diacids have common names accepted by IUPAC.

5 Structure and Properties of Carboxylic Acid The carbon atom of a carboxylic acid group is sp 2 hybridized and therefore exhibits trigonal planar geometry with bond angles that are nearly 120 Carboxylic acids can form two hydrogen-bonding interactions, allowing molecules to associate with each other in pairs.

6 Acidity of Carboxylic Acids Carboxylate salts are ionic and are therefore more water-soluble than their corresponding carboxylic acids. Carboxylate ions are named by replacing the suffix ic acid with ate ; for example:

7 When dissolved in water, an equilibrium is established in which the carboxylic acid and the carboxylate ion are both present. In most cases, the equilibrium significantly favors the carboxylic acid with a Ka usually around 10-4 or In other words, the pka of most carboxylic acids is between 4 and 5.

8 Carboxylic Acids at Physiological ph Our blood is buffered to a ph of approximately 7.3, a value referred to as physiological ph. When dealing with buffered solutions, you may recall the Henderson-Hasselbalch equation. When the pka value of an acid is equivalent to the ph of a buffered solution into which it is dissolved, thenthe ratio of the concentrations of conjugate base and acid will be 1. In other words, a carboxylic acid and its conjugate base will be present in approximately equal amounts when dissolved in a solution that is buffered such that ph = pka of the acid.

9 Now let s apply this equation to carboxylic acids at physiological ph (7.3), so that we can determine which form predominates (the carboxylic acid or the carboxylate ion). Recall that carboxylic acids generally have a pka value between 4 and 5. Therefore, at physiological ph: The ratio of the concentrations of the carboxylate ion and the carboxylic acid will be approximately 1000 : 1. That is, carboxylic acids will exist primarily as carboxylate salts at physiological ph. For example, pyruvic acid exists primarily as pyruvate ion at physiological ph.

10 Substituent Effects on Acidity

11 Preparation of Carboxylic Acids Hydrolysis of Nitriles Carboxylation of Grignard Reagents

12 Reactions of Carboxylic Acids

13 Under such conditions, the aldehyde cannot be isolated. Instead, it is further attacked by LAH to form an alkoxide, which is then protonated when H3O+ is introduced into the reaction flask. An alternative method for reducing carboxylic acids involves the use of borane (BH 3 ). Selectivity

14 Introduction to Carboxylic Acid Derivatives Classes of Carboxylic Acid Derivatives In the previous section, we learned about the reaction between a carboxylic acid and LAH. This reaction is a reduction, because the carbon atom of the carboxylic acid group is reduced in the process: Carboxylic acids also undergo many other reactions that do not involve a change in oxidation state:

15 Carboxylic Acid Derivatives in Nature

16 Naming Acid Halides Acid halides are named as derivatives of carboxylic acids by replacing the suffix ic acid with yl halide : When an acid halide group is connected to a ring, the suffix carboxylic acid is replaced with carbonyl halide ; for example:

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22 Reactivity of Carboxylic Acid Derivatives

23 Nucleophilic Acyl Substitution

24 When a nucleophile attacks a carbonyl group to form a tetrahedral intermediate, the carbonylgroup will always be re-formed, if possible, but H - and C - are generally not expelled as leaving groups. Chloride is more stable than methoxide and is therefore a better leaving group, so the carbonyl will likely re-form to expel the chloride ion

25 In acidic conditions, avoid formation of a strong base. In basic conditions, such as hydroxide or methoxide, avoid formation of a strong acid.

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28 Preparation and Reactions of Acid Chlorides

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34 Preparation and Reactions of Acid Anhydrides Preparation of Acid Anhydrides

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