Carboxylic Acids, Esters, and Amides

Carboxylic acids, esters, and amides all contain a carbonyl group that is bonded to an oxygen or nitrogen atom. As we shall learn in later chapters, all of these functional groups are interconvertible by appropriately chosen reactions. 

Carboxylic acids have a carbonyl group bonded to a hydroxyl group, and they have the O O 

Examples of carboxylic acids are formic acid, acetic acid, and benzoic acid  

Formic acid is an irritating liquid produced by ants. (The sting of the ant is caused, in part, by formic acid being injected under the skin. Formic is the Latin word for ant.) Acetic acid, the substance responsible for the sour taste of vinegar, is produced when certain bacteria act on the ethyl alcohol of wine and cause the ethyl alcohol to be oxidized by air. 

When formic acid donates the proton from its oxygen to a base, a formate ion is the result. Write another resonance structure for formic acid and for the formate ion. Which species, formic acid or the formate ion, would be most stabilized by resonance  

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Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

Notice in the list of Lewis bases just given that some compounds, such as carboxylic acids, esters, and amides, have more than one atom ivith a lone pair of electrons and can therefore react at more than one site. Acetic acid, for example, can be protonated either on the doubly bonded oxygen atom or on the singly bonded oxygen atom. Reaction normally occurs only once in such instances, and the more stable of the two possible protonation products is formed. For acetic add, protonation by reaction with sulfuric acid occurs on... 

Most carbonyl compounds exist almost exclusively in the keto form at equilibrium, and it s usually difficult to isolate the pure enol. For example, cyclohexanone contains only about 0.0001% of its enol tautomer at room temperature, and acetone contains only about 0.000 000 1% enol. The percentage of enol tautomer is even less for carboxylic acids, esters, and amides. Even though enols are difficult to isolate and are present only to a small extent at equilibrium., they are nevertheless responsible for much of the chemistry of carbonyl compounds because they are so reactive. 

I2 or with a carbon tetrahalide. " Carboxylic acids, esters, and amides have been... 

Disubstituted 2,4-cyclohexadienones (112) undergo photoinduced electrocyclic ring opening to the transient ketene derivatives 113, which can be trapped by nucleophiles to prepare the corresponding carboxylic acid derivatives (114 equation 44)196 197 j le reaction has been employed successfully for the synthesis of various carboxylic acids, esters and amides. 

Before discussmg the mechanism of cleavage of carboxylic acid esters and amides by hydrolases, some chemical principles are worth recalling. The chemical hydrolysis of carboxylic acid derivatives can be catalyzed by acid or base, and, in both cases, the mechanisms involve addition-elimination via a tetrahedral intermediate. A general scheme of ester and amide hydrolysis is presented in Fig. 3. / the chemical mechanisms of ester hydrolysis will be... 

Fig. 3.1. General scheme for chemical hydrolysis of carboxylic acid esters and amides. Pathway a Proton (general acid) catalyzed hydrolysis. Pathway b HO (general base) catalyzed...

Kinetic Enolization of Carboxylic Acid Esters and Amides (Scheme 7)... 

The linker group is immobilized as a urethane to the amino-functionalized carrier (59). It facilitates the attachment of a variety of molecules such as alkyl halides, alcohols or amines bound as carboxylic acid esters and amides. 

Electrophilic additions to 7t-deficient heterocycles are less common than those to 7t-excessive heterocycles. However, intramolecular electrophilic cyclizations have been used to access the heterocycles of interest in this chapter <1996CHEC-II(7)49>. Recent examples include the preparation of a pyrrolo[2,3-f]pyrazole 165 by acid-catalyzed condensation of 163 and 164 (Equation 37) <1999SC311> and the reaction of 3-(4-pyrazolyl)acrylic acids 166 with excess thionyl chloride in the presence of benzyltriethylammonium chloride (BTEAC) to afford 4-chlorothieno[2,3-f]pyrazole-5-carbonyl chlorides 167 (Equation 38) <2003RJ0893, 2003ZOK942>. In the latter case, the reaction products were readily manipulated to prepare corresponding carboxylic acids, esters, and amides using standard procedures. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

See also page 236, Section 8, for ene reactions leading to unsaturated carboxylic acids, esters and amides. 

T FIGURE 23.5 Carbonyl compounds can be classified into two categories. Aldehydes and ketones are less polar, while carboxylic acids, esters, and amides are more polar. 

Carboxylic acids, esters, and amides have their carbonyl groups bonded to an atom (O or N) that strongly attracts electrons. All three families undergo carbonyl-group substitution reactions, in which a group we can represent as -Y substitutes for the -OH, -OC, or -N group of the carbonyl reactant. 

The enol tautomers of many ketones and aldehydes, carboxylic acids, esters and amides, ketenes, as well as the keto tautomers of phenols have since all been generated by flash photolysis to determine the pH rate profiles for keto-enol interconversion. Equilibrium constants of enolization, KB, were determined accurately as the ratio of the rate constants of enolization, kE, and of ketonization, kK, Equation (1). 

This reaction can be extended to unsaturated nitriles, eg, acrylonitrile, which can give trihalostannyl-functional carboxylic acids, esters, and amides by the proper choice of solvents and reaction conditions (156). 

The Reduction of Carboxylic Acids, Esters and Amides with Sml2... 

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