15-1 Chemistry 2060, Spring 2060, LSU Chapter 15: Functional Derivatives of Carboxylic Acids Sections

15-2 Chemistry 2060, Spring 2060, LSU Sections Chapter 15: Aldehydes and Ketones 1.Introduction 2.Structure and nomenclature 3.Characteristic properties 4.Reaction with water: hydrolysis 5.Reaction with alcohols 6.Reactions with ammonia and amines 7.Interconversion of functional derivatives 8.Esters with Grignard reagents 9.Reduction

15-3 Chemistry 2060, Spring 2060, LSU Carboxyl Derivatives In this chapter, we study four classes of organic compounds under the general formula of each is a drawing to help you see how it is related to the carboxyl group

15-4 Chemistry 2060, Spring 2060, LSU Acid Chlorides The functional group of an acid halide is an acyl group bonded to a halogen the most widely used are the acid chlorides -ic acid -yl chlorideto name, change the suffix -ic acid to -yl chloride

15-5 Chemistry 2060, Spring 2060, LSU Acid Anhydrides The functional group of an acid anhydride is two acyl groups bonded to an oxygen atom the anhydride may be symmetrical (two identical acyl groups) or mixed (two different acyl groups) acidanhydrideto name, replace acid of the parent acid by anhydride

15-6 Chemistry 2060, Spring 2060, LSU Acid Anhydrides A phosphoric acid anhydride contains two phosphoryl groups bonded to an oxygen atom shown here are two phosphoric anhydrides each is shown on the right as it would be ionized at pH 7.4, the pH of blood

15-7 Chemistry 2060, Spring 2060, LSU Esters The functional group of an ester is an acyl group bonded to -OR or -OAr name the alkyl or aryl group bonded to oxygen followed by the name of the acid -ic acid-atechange the suffix -ic acid to -ate

15-8 Chemistry 2060, Spring 2060, LSU Lactones Lactone: a cyclic ester -ic acid-olactoneIUPAC: name the parent carboxylic acid, drop the suffix -ic acid, and add -olactone the location of the oxygen atom on the carbon chain is commonly indicated by a Greek letterthe location of the oxygen atom on the carbon chain is commonly indicated by a Greek letter

15-9 Chemistry 2060, Spring 2060, LSU Phosphoric esters Phosphoric acid forms mono-, di-, and triesters name by giving the name of the alkyl or aryl group(s) bonded to oxygen followed by the word phosphate in more complex phosphate esters, it is common to name the organic molecule followed by phosphate

15-10 Chemistry 2060, Spring 2060, LSU Amides The functional group of an amide is an acyl group bonded to a trivalent nitrogen ic acid -amideIUPAC: drop -ic acid from the name of the parent acid and add -amide N-if the amide nitrogen is bonded to an alkyl or aryl group, name the group and show its location on nitrogen by N-

15-11 Chemistry 2060, Spring 2060, LSU Lactam Lactam: a cyclic amide -ic acid -lactamname the parent carboxylic acid, drop the suffix -ic acid and add -lactam the location of the nitrogen atom in the ring is commonly indicated by a Greek letter, , , etc. 6-hexanolactam is an intermediate in the synthesis of nylon 6 (Section 17.5A)

15-12 Chemistry 2060, Spring 2060, LSU The Penicillins The penicillins are a family of  -lactam antibiotics one of the first discovered was penicillin G

15-13 Chemistry 2060, Spring 2060, LSU The Penicillins amoxicillin, a  -lactam antibiotic

15-14 Chemistry 2060, Spring 2060, LSU Cephalosporins The cephalosporins are also  -lactam antibiotics

15-15 Chemistry 2060, Spring 2060, LSU Characteristic Reactions Nucleophilic acyl substitution: an addition- elimination sequence resulting in substitution of one nucleophile for another the reaction depends on having a suitable leaving group bonded to the acyl carbon, here indicated Lv

15-16 Chemistry 2060, Spring 2060, LSU Characteristic Reactions in the general reaction, we showed the nucleophile as an anion; this need not be the case neutral molecules such as water, alcohols, ammonia, and amines can also serve as nucleophiles in the general reaction, we showed the leaving group as an anion to illustrate an important point about them: the weaker the base, the better the leaving group

15-17 Chemistry 2060, Spring 2060, LSU Characteristic Reactions halide ion is the weakest base and the best leaving group; acid halides are the most reactive toward nucleophilic acyl substitution amide ion is the strongest base and the poorest leaving group; amides are the least reactive toward nucleophilic acyl substitution

15-18 Chemistry 2060, Spring 2060, LSU Hydrolysis - Acid Chlorides low-molecular-weight acid chlorides react rapidly with water higher molecular-weight acid chlorides are less soluble in water and react less readily

15-19 Chemistry 2060, Spring 2060, LSU Hydrolysis - Acid Anhydrides low-molecular-weight acid anhydrides react readily with water to give two molecules of carboxylic acid higher-molecular-weight acid anhydrides also react with water, but less readily

15-20 Chemistry 2060, Spring 2060, LSU Hydrolysis - Esters Esters are hydrolyzed only slowly, even in boiling water Hydrolysis becomes more rapid if they are heated with either aqueous acid or aqueous base Hydrolysis in aqueous acid is the reverse of Fischer esterification

15-21 Chemistry 2060, Spring 2060, LSU Hydrolysis - Esters Hydrolysis of an ester in aqueous base is often called saponification each mole of ester hydrolyzed requires 1 mole of base; for this reason, ester hydrolysis in aqueous base is said to be base promoted base-promoted ester hydrolysis involves formation of a tetrahedral carbonyl addition intermediate followed by its collapse

15-22 Chemistry 2060, Spring 2060, LSU Hydrolysis - Esters step 1: addition of hydroxide ion to the carbonyl carbon step 2: collapse of the addition intermediate step 3: proton transfer completes the reaction

15-23 Chemistry 2060, Spring 2060, LSU Hydrolysis - Esters There are two major differences between acid- catalyzed and base-promoted ester hydrolysis 1. for acid-catalyzed hydrolysis, acid is required in only catalytic amounts; for base-promoted hydrolysis, base is required in equimolar amounts 2. hydrolysis of an ester in aqueous acid is reversible; base-promoted hydrolysis is irreversible

15-24 Chemistry 2060, Spring 2060, LSU Hydrolysis - Amides Hydrolysis of an amide requires much more vigorous conditions than hydrolysis of an ester hydrolysis in aqueous acid requires 1 mole of acid for each mole of amide the products are a carboxylic acid and an ammonium or an amine salt

15-25 Chemistry 2060, Spring 2060, LSU Hydrolysis - Amides hydrolysis of an amide in aqueous base requires 1 mole of base per mole of amide the products are a carboxylate salt and an amine

15-26 Chemistry 2060, Spring 2060, LSU Hydrolysis A summary

15-27 Chemistry 2060, Spring 2060, LSU Reaction with Alcohols Acid chlorides react with alcohols to give an ester and HCl

15-28 Chemistry 2060, Spring 2060, LSU Reaction with Alcohols Acid anhydrides react with alcohols to give 1 mole of ester and 1 mole of carboxylic acid aspirin is prepared by the following reaction:

15-29 Chemistry 2060, Spring 2060, LSU Reaction with Alcohols Esters undergo an exchange reaction called transesterification the exchange is acid catalyzed the original -OR group is exchanged for a new -OR group

15-30 Chemistry 2060, Spring 2060, LSU Reaction with Alcohols Amides to not react with alcohols under any conditions Summary of reactions with alcohols

15-31 Chemistry 2060, Spring 2060, LSU Reaction with NH 3 and Amines Acid halides react with ammonia, 1° amines, and 2° amines to form amides 2 moles of the amine are required per mole of acid chloride; one to form the amide and one to neutralize the HCl formed

15-32 Chemistry 2060, Spring 2060, LSU Reaction with NH 3 and Amines Acid anhydrides react with ammonia, and with 1° and 2° amines to form amides 2 moles of ammonia or amine are required; one to form the amide and one to neutralize the carboxylic acid byproduct here the reaction is broken into two steps

15-33 Chemistry 2060, Spring 2060, LSU Reaction with NH 3 and Amines Esters react with ammonia, and with 1° and 2° amines to form amides esters are less reactive than either acid halides or acid anhydrides Amides do not react with ammonia, or with 1° or 2° amines

15-34 Chemistry 2060, Spring 2060, LSU Reaction with NH 3 & Amines Summary

15-35 Chemistry 2060, Spring 2060, LSU Interconversion interconversion of functional groups

15-36 Chemistry 2060, Spring 2060, LSU Esters with Grignard Reagents a formic ester with 2 moles of Grignard reagent followed by hydrolysis gives a 2° alcohol reaction of an ester other than a formate gives a 3° alcohol

15-37 Chemistry 2060, Spring 2060, LSU Esters with Grignard Reagents Steps 1 and 2 Steps 3 and 4

15-38 Chemistry 2060, Spring 2060, LSU Reduction esters are reduced by LiAlH 4 to two alcohols the alcohol derived from the carbonyl group is primary NaBH 4 does not normally reduce esters, but it does reduce aldehydes and ketones

15-39 Chemistry 2060, Spring 2060, LSU Reduction LiAlH 4 reduction of an amide gives a 1°, 2°, or 3° amine, depending on the degree of substitution of the amide

15-40 Chemistry 2060, Spring 2060, LSU Some Interconversions from Example 15.7