Carboxylic acid anhydrides resonance

Note any very low field resonances (160 to 220 5/ppm), which are associated with carbonyl and ether carbons. Carboxylic acids, anhydrides, esters, amides, acyl halides and ethers are all found in the range 160 to 180 5/ppm, whilst aldehydes and ketones lie between 180 and about 220 5/ppm. 

The negatively charged oxygen substituent is a powerful electron donor to the carbonyl group Resonance m carboxylate anions is more effective than resonance m carboxylic acids acyl chlorides anhydrides thioesters esters and amides... 

Carboxylic acids can be activated in situ as mixed anhydrides B (Figure 6.14) that are mixed anhydrides of a carboxylic acid and a carbonic acid half ester. As can be seen from Table 6.1, in anhydrides of this type the C=0 double bond of the carboxylic acid moiety is stabilized less by resonance than the C=0 double bond of the carbonic acid moiety. Therefore, a nucleophile chemoselectively reacts with the carboxyl carbon of the carboxylic and not the carbonic acid ester moiety. 

Thus, the carbonyl group of an acid chloride and anhydride, which are least stabilized by resonance, absorb at higher frequency than the carbonyl group of an amide, which is more stabilized by resonance. Table 22.4 lists specific values for the carbonyl absorptions of the carboxylic acid derivatives. 

Voltammetric data for ester reductions are available for several aromatic esters [51-54], and in particular cyclic voltammetry shows clearly that in the absence of proton donors reversible formation of anion radical occurs [51]. In dimethylfonnamide (DMF) solution the peak potential for reduction of methyl benzoate is —2.29 V (versus SCE) for comparison dimethyl terephthalate reduces at —1.68 V and phthalic anhydride at —1.25 V [4]. Half-wave potentials for reduction of aromatic carboxylate esters in an unbuffered solution of pH 7.2 are linearly correlated with cr values [51] electron-withdrawing substituents in the ring or alkoxy group shift Ei/o toward less negative potentials. Generally, esters seem to be more easily reducible than the parent carboxylic acids. Anion radicals of methyl, ethyl, and isopropyl benzoate have been detected by electron paramagnetic resonance (epr) spectroscopy upon cathodic reduction of these esters in acetonitrile-tetrapro-pylammonium perchlorate [52]. The anion radicals of several anhydrides, including phthalic anhydride, have similarly been studied [55]. 

This section deals with the chemical shifts of the carboxylic anhydrides. As a group, the anhydrides are very reactive and readily decompose to the corresponding carboxylic acid in the presence of the traces of water found in DMSO-d6, polysol and acetone-d6. In general, the carbonyl chemical shift of the anhydride resonates at a higher field than that of the carboxylic acid. 

Consequently, aldehydes and ketones are not as reactive as carbonyl compounds in which Y is a very weak base (acyl halides and acid anhydrides), but are more reactive than carbonyl compounds in which Y is a relatively strong base (carboxylic acids, esters, and amides). A molecular orbital explanation of why resonance electron donation decreases the reactivity of the carbonyl group is given in Section 17.15. 

This chapter will revisit the lUPAC nomenclature system for aldehydes, ketones, and carboxylic acids, as well as introduce nomenclature for the four main acid derivatives acid chlorides, anhydrides, esters, and amides. The chapter will show the similarity of a carbonyl and an alkene in that both react with a Br0nsted-Lowry acid or a Lewis acid. The reaction of a carbonyl compound with an acid will generate a resonance stabilized oxocarbenium ion. Ketones and aldehydes react with nucleophiles by what is known as acyl addition to give an alkoxide product, which is converted to an alcohol in a second chemical step. Acid derivatives differ from aldehydes or ketones in that a leaving group is attached to the carbonyl carbon. Acid derivatives react with nucleophiles by what is known as acyl substitution, via a tetrahedral intermediate. 

In principle, this reaction occurs with carboxylic acids, where X = OH in 72. The reaction occurs for carboxylic acid derivatives 56-60, where the X group in 72 and in 73 is Cl for an acid chloride, O2CR for an anhydride, OR for an ester, or NR2 for an amide. For these derivatives 73, a heteroatom is attached to the 6+ carbon, and there is additional resonance stabilization due to the lone electron pairs on these atoms. How oxocarbenium ions might react after they are formed has not been discussed, but it is clear that the carbonyl group of an acid derivative can react as a base in the presence of an appropriate acid. Reactions of oxocarbenium ions are discussed in Chapters 18 and 20. 

When acid derivative 2 reacts with sulfuric acid, the oxygen atom is the base and the conjugate acid product of this acid-base reaction is oxocarbenium ion 3, which is resonance stabilized. When 2 is an acid chloride, anhydride, ester, or amide, a heteroatom is attached to the positive carbon in 3. As in Chapter 18 (Section 18.1), the acid-base reaction of the carbonyl unit in 2 to give 3 facilitates reactions with nucleophiles. The reaction of intermediate 3 with a nucleophile ( Y) gives tetrahedral intermediate 4 contrary to acyl addition, reaction 4 contains an X group that can function as a leaving group. Loss of X leads to the final product of this reaction 5. If the nucleophile ( Y) is hydroxide, compormd 5 is the carboxylic acid (X = OH). If the nucleophile Y is an alcohol, the product 5 is an ester, and if Y is an amine, the product 5 is an amide. This first reaction is therefore the acid-catalyzed acyl substitution reaction of acid derivatives. 

An ester is hydrolyzed with aqueous acid as well as with aqueous hydroxide. Under acidic conditions, the mechanism of ester hydrolysis is similar to that of acid chlorides and acid anhydrides, as shown previously. When ethyl butanoate (29) is treated with an acid catalyst in water, the products are carboxylic acid (butanoic acid, 6) and ethanol. The OH unit in this acid is clearly derived from the water, and the OEt rmit in ethanol is derived from the OEt unit of the ester. It is known that water does not react directly with 29 to give 7, so the acid catalyst must facilitate the reaction. This, of course, indicates that 29 reacts as a base with the acid catalyst to give the resonance-stabilized oxocarbenium ion 30. 

We have seen throughout the past several sections that acid chlorides are most reactive toward nucleophilic acyl substitution, followed by acid anhydrides and esters the least reactive are amides. Carboxylate anions are negatively charged and therefore repel nucleophiles the resonance in these species is quite stabilizing. Both of these factors make carbo>qrlate anions essentially inert to nucleophilic acyl substitution (hence, we have not examined them to this point in the chapter). Another useful way to think about the reactions of the functional derivatives of carboxylic acids is summarized in Figure 18.2. 

The amoimt of resonance stabilization varies in these derivatives of carboxylic acids. The acid halides are the least stabflized, followed by anhydrides, the esters and acids, and finally amides, which are the most stabilized. Now two questions arise How do we know the relative amoimt of resonance stabilization, and what factors contribute to the order The first question must wait until the next section on spectroscopy, but we can deal with the second question right here. 

The acid chloride carbonyl is the strongest of the acid derivatives, with the most double-bond character, so its C O stretch appears at the highest frequency. Anhydrides, esters, and carboxylic acids are next. Amides, in which the contribution from the dipolar resonance form is strongest, and the sing/e-bond character of the carbonyl group is greatest, have the lowest carbonyl stretching frequencies (Table 18.2). 

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