Carbonyl Compounds I 17 Nucleophilic Acyl Substitution he carbonyl group—a carbon double bonded to T an oxygen—is probably the most important functional group found in organic compounds. Compounds containing an acyl chloride carbonyl groups— called carbonyl compounds— Penicillin G are abundant in nature. Many play important roles in biological processes. Hormones, vitamins, amino acids, drugs, and flavorings are just a few of the carbonyl compounds that affect us daily. An acyl group consists of a car- bonyl group attached to an alkyl group or to an aryl group. O O O C C C R Ar a carbonyl group acyl groups an ester The substituents attached to the acyl group strongly affect the reactivity of carbonyl compounds. Carbonyl compounds can be divided into two classes. Class I carbonyl compounds are those in which the acyl group is attached to an atom or a group that can be replaced by another group. Carboxylic acids, acyl halides, acid anhydrides, esters, and amides belong to this class. All of these compounds contain a group ( ¬ OH, ¬ Cl, ¬ Br, ¬ O(CO)R, ¬ OR, ¬ NH2 , ¬ NHR, or ¬ NR2) that can be replaced by a nucleophile. Acyl halides, acid anhydrides, esters, and amides are all called a carboxylic acid carboxylic acid derivatives because they differ from a carboxylic acid only in the na- ture of the group that has replaced the OH group of the carboxylic acid. compounds with groups that can be replaced by a nucleophile O O O O C C C C R OH R OR′ R O R′ an amide a carboxylic acidan ester an acid anhydride 670 Section 17.1 Nomenclature 671 compounds with groups that can be replaced by a nucleophile O O O O O C C C C C ′ ′ R Cl R Br R NH2 R NHR R NR 2 an acyl chloride an acyl bromide amides acyl halides Class II carbonyl compounds are those in which the acyl group is attached to a group that cannot be readily replaced by another group. Aldehydes and ketones belong to this class. The ¬ H and alkyl or aryl ( ¬ R or ¬ Ar) groups of aldehydes and ke- tones cannot be replaced by a nucleophile. cannot be replaced by a nucleophile O O C C R H R′ R an aldehyde a ketone In Chapter 10, we saw that the likelihood of a group’s being replaced by another group depends on the relative basicities of the two groups: The weaker the basicity of a group, the better its leaving ability. Recall from Section 10.3 that weak bases are good leaving groups because weak bases do not share their electrons as well as strong bases do. The pKa values of the conjugate acids of the leaving groups of various carbonyl compounds are listed in Table 17.1. Notice that the acyl groups of Class I carbonyl com- pounds are attached to weaker bases than are the acyl groups of Class II carbonyl compounds. (Remember that the lower the pKa, the stronger the acid and the weaker its conjugate base.) The ¬ H of an aldehyde and the alkyl or aryl ( ¬ R or ¬ Ar) group of a ketone are too basic to be replaced by another group. This chapter discusses the reactions of Class I carbonyl compounds. We will see that these compounds undergo substitution reactions because they have an acyl group attached to a group that can be replaced by a nucleophile. The reactions of aldehydes and ketones will be considered in Chapter 18. Because aldehydes and ketones have an acyl group attached to a group that cannot be replaced by a nucleophile, we can cor- rectly predict that these compounds do not undergo substitution reactions. 17.1 Nomenclature Carboxylic Acids In systematic nomenclature, a carboxylic acid is named by replacing the terminal “e” of the alkane name with “oic acid.” For example, the one-carbon alkane is methane,so the one-carbon carboxylic acid is methanoic acid. O O O O C C C C H OH CH3 OH CH3CH2 OH CH3CH2CH2 OH systematic name: methanoic acid ethanoic acid propanoic acid butanoic acid common name: formic acid acetic acid propionic acid butyric acid O O O O C C C C CH3CH2CH2CH2 OH CH3CH2CH2CH2CH2 OH CH2 CH OH OH pentanoic acid hexanoic acid propenoic acid benzenecarboxylic acid valeric acid caproic acid acrylic acid benzoic acid 672 CHAPTER 17 Carbonyl Compounds I Table 17.1 The pKa Values of the Conjugate Acids of the Leaving Groups of Carbonyl Compounds Carbonyl Leaving Conjugate acid of compound group the leaving group pKa Class I O C − R Br Br HBr −9 O C − R Cl Cl HCl −7 O O O O C C C C − R O R O R ROH ~3–5 O C − R OR′ OR′ R′OH ~15–16 O C − R OH OH H2O 15.7 O C − R NH2 NH2 NH3 36 Class II O C − R H H H2 ~40 O C − R R R RH ~50 Carboxylic acids containing six or fewer carbons are frequently called by their com- mon names. These names were chosen by early chemists to describe some feature of the compound, usually its origin. For example, formic acid is found in ants, bees, and other stinging insects; its name comes from formica, which is Latin for “ant.” Acetic acid—contained in vinegar—got its name from acetum, the Latin word for “vinegar.” Propionic acid is the smallest acid that shows some of the characteristics of the larger fatty acids; its name comes from the Greek words pro (“the first”) and pion (“fat”). Bu- tyric acid is found in rancid butter; the Latin word for “butter” is butyrum. Caproic acid is found in goat’s milk, and if you have the occasion to smell both a goat and caproic acid, you will find that they have similar odors. Caper is the Latin word for “goat.” In systematic nomenclature, the position of a substituent is designated by a number. The carbonyl carbon of a carboxylic acid is always the C-1 carbon. In common nomen- clature, the position of a substituent is designated by a lowercase Greek letter, and the carbonyl carbon is not given a designation. The carbon adjacent to the carbonyl carbon is the A-carbon, the carbon adjacent to the a-carbon is the b-carbon, and so on. O O alpha ؍ A beta C C ؍ B 1 ؍ G gamma CH3CH2CH2CH2CH2 OH CH3CH2CH2CH2CH2 OH delta 6 5 4 3 2 ؍ D ؍ ` epsilon systematic nomenclature common nomenclature Section 17.1 Nomenclature 673 Take a careful look at the following examples to make sure that you understand the difference between systematic (IUPAC) and common nomenclature: O O O CH3O Br Cl C C C CH3CH2CH OH CH3CH2CHCH2 OH CH3CH2CHCH2CH2 OH systematic name: 2-methoxybutanoic acid 3-bromopentanoic acid 4-chlorohexanoic acid common name: -methoxybutyric acid -bromovaleric acid -chlorocaproic acid The functional group of a carboxylic acid is called a carboxyl group. O C COOH CO2H OH a carboxyl group carboxyl groups are frequently shown in abbreviated forms Carboxylic acids in which a carboxyl group is attached to a ring are named by adding “carboxylic acid” to the name of the cyclic compound. O COOH C COOH COOH OH CH3 COOH cyclohexanecarboxylic acid trans-3-methylcyclopentanecarboxylic 1,2,4-benzenetricarboxylic acid acid Acyl Halides Acyl halides are compounds that have a halogen atom in place of the OH group of a 3-D Molecules: carboxylic acid. The most common acyl halides are acyl chlorides and acyl bromides. trans-3-Methylcyclo- Acyl halides are named by using the acid name and replacing “ic acid” with “yl chlo- pentanecarboxylic acid; ride” (or “yl bromide”). For acids ending with “carboxylic acid,” “carboxylic acid” is Acetic anhydride replaced with “carbonyl chloride” (or “bromide”). O O O C CH3 Cl C C CH3 Cl CH3CH2CHCH2 Br systematic name: ethanoyl chloride 3-methylpentanoyl bromide cyclopentanecarbonyl common name: acetyl chloride -methylvaleryl bromide chloride Acid Anhydrides Loss of water from two molecules of a carboxylic acid results in an acid anhydride. “Anhydride” means “without water.” O O O O C C C C ROHHO R RRO an acid anhydride If the two carboxylic acid molecules forming the acid anhydride are the same, the anhydride is a symmetrical anhydride. If the two carboxylic acid molecules are differ- ent, the anhydride is a mixed anhydride. Symmetrical anhydrides are named by using the acid name and replacing “acid” with “anhydride.” Mixed anhydrides are named by stating the names of both acids in alphabetical order, followed by “anhydride.” 674 CHAPTER 17 Carbonyl Compounds I O O O O C C C C CH3 O CH3 CH3 O H systematic name: ethanoic anhydride ethanoic methanoic anhydride common name: acetic anhydride acetic formic anhydride a symmetrical anhydride a mixed anhydride Esters An ester is a compound that has an OR¿ group in place of the OH group of a carboxylic acid. In naming an ester, the name of the group (R¿) attached to the carboxyl oxygen is stated first, followed by the name of the acid, with “ic acid” replaced by “ate.” carbonyl oxygen O C R OR′ carboxyl oxygen O O O O Br C C C C CH3 OCH2CH3 CH3CH2 O CH3CHCH2 OCH3 OCH2CH3 systematic name: ethyl ethanoate phenyl propanoate methyl 3-bromobutanoate ethyl cyclohexanecarboxylate common name: ethyl acetate phenyl propionate methyl -bromobutyrate Salts of carboxylic acids are named in the same way. The cation is named first, followed by the name of the acid, again with “ic acid” replaced by “ate.” Tutorial: O O O Nomenclature of carboxylic C C C acids and their derivatives − + − + − + H O Na CH3 O K O Na systematic name: sodium methanoate potassium ethanoate sodium benzenecarboxylate common name: sodium formate potassium acetate sodium benzoate Cyclic esters are called lactones.