Objectives After completing this section, you should be able to describe in detail the methods of preparing carboxylic acids discussed in previous chapters: the oxidation of alkylbenzenes. the oxidative cleavage of alkenes. the oxidation of primary alcohols and aldehydes. discuss, in detail, the hydrolysis of nitriles: write an equation to illustrate the preparation of a carboxylic acid through nucleophilic attack by cyanide ion on an alkyl halide and hydrolysis of the nitrile which results. identify the carboxylic acid formed from the hydrolysis of a given nitrile, or from the reaction of a given alkyl halide with cyanide ion followed by hydrolysis of the resulting nitrile. identify the alkyl halide needed to prepare a given carboxylic acid by the formation and subsequent hydrolysis of a nitrile. identify the reagents needed to convert a given alkyl halide into a carboxylic acid containing one more carbon atom. discuss, in detail, the carboxylation of Grignard reagents: write an equation describing the formation of a carboxylic acid from a Grignard reagent. identify the carboxylic acid obtained through the treatment of a given Grignard reagent with carbon dioxide followed by dilute acid. identify the Grignard reagent (or the alkyl halide required to form the Grignard reagent) that must be used to produce a given carboxylic acid by reaction with carbon dioxide. write the detailed mechanism for the formation of a carboxylic acid using a Grignard reagent. Study Notes Review the methods of obtaining carboxylic acids presented in earlier sections: oxidation of aromatic compounds—Section 16.9. oxidative cleavage of alkenes—Section 8.8. oxidation of primary alcohols and aldehydes—Sections 17.7 and 19.3. The carbon atom of a carboxyl group has a high oxidation state. It is not surprising, therefore, that many of the chemical reactions used for their preparation are oxidations. Such reactions have been discussed in previous sections of this text, and the following diagram summarizes most of these. To review the previous discussion of any of these reaction classes simply click on the number ( 1 to 4 ) or descriptive heading for the group. Two other useful procedures for preparing carboxylic acids involve hydrolysis of nitriles and carboxylation of organometallic intermediates. As shown in the following diagram, both methods begin with an organic halogen compound and the carboxyl group eventually replaces the halogen. Both methods require two steps, but are complementary in that the nitrile intermediate in the first procedure is generated by a S N 2 reaction, in which cyanide anion is a nucleophilic precursor of the carboxyl group. The hydrolysis may be either acid or base-catalyzed, but the latter give a carboxylate salt as the initial product. In the second procedure the electrophilic halide is first transformed into a strongly nucleophilic metal derivative, and this adds to carbon dioxide (an electrophile). The initial product is a salt of the carboxylic acid, which must then be released by treatment with strong aqueous acid. An existing carboxylic acid may be elongated by one methylene group, using a homologation procedure called the Arndt-Eistert reaction . To learn about this useful method Click Here. Worked Example 20.5.1 Thus far this chapter has discussed three main methods for the creation of a carboxylic acid functional group: the oxidation of a 1 o alcohol, the carboxylation of a Grignard reagent, and the hydrolysis of a nitrile. Select one of these three methods to perform the following transformation. Briefly explain why the other two methods would be unsuccessful. a) Tert-Butyl Bromide → 2,2-Dimethylpropanoic acid. b) Benzyl Bromide → Benzoic Acid c) 3-Bromo-1-propanol → 4-Hydroxybutanoic acid Solution a) The product contains one more carbon than the reactant so the oxidation of a 1 o alcohol would be an ineffective method. Also, the reactant contains a tertiary halide, so the S N 2 reaction required to form a nitrile would not be possible. The carboxylation of a Grignard reagent would be the most effective method because it allows for the addition of a carbon, it is not severely affected by the sterics of the tertiary halide, and there are no incompatible functional groups. b) The product and reactant have the same number of carbons so both the carboxylation of a Grignard reagent and hydrolysis of a nitrile would be ineffective for this conversion. Benzyl bromide is a primary alkyl halide which can easily be converted to a primary alcohol by an S N 2 reaction with NaOH. Once formed, the primary alcohol can be converted to a carboxylic acid using an oxidation reaction. c) The product contains one more carbon than the reactant so the oxidation of a primary alcohol would not be an effective method. Also, the carboxylation of a Grignard reagent would not be an effect method because the presence of an incompatible alcohol functional group in the reactant. The reactant contains a primary halogen which can readily be converted to a nitrile by an S N 2 reaction with NaCN. The resulting nitrile can be converted to a carboxylic acid through hydrolysis. Exercises Exercise 20.5.1 Show how the following molecules can be used to synthesize benzoic acid: a) b) c) Answer a) b) c) Exercise 20.5.2 Please give the structure of the bromide required to make the following using the carboxylation of a Grignard reagent: a) b) c) Answer a) b) c) Exercise 20.5.3 Please give the possible reactants for the following reactions: a) There are at least four possible answers for question a. b) Answer a) b)