1. John E. McMurry www.cengage.com/chemistry/mcmurry Paul D. Adams University of Arkansas Chapter 20 Carboxylic Acids and Nitriles

2.  Starting materials for acyl derivatives (esters, amides, and acid chlorides)  Abundant in nature from oxidation of aldehydes and alcohols in metabolism  Acetic acid, CH 3 CO 2 H, - vinegar  Butanoic acid, CH 3 CH 2 CH 2 CO 2 H (rancid butter)  Long-chain aliphatic acids from the breakdown of fats The Importance of Carboxylic Acids (RCO 2 H)

3.  Carboxylic acids present in many industrial processes and most biological processes  They are the starting materials from which other acyl derivatives are made  An understanding of their properties and reactions is fundamental to understanding organic chemistry Why this Chapter?

4.  Carboxylic Acids, RCO 2 H  If derived from open-chain alkanes, replace the terminal - e of the alkane name with -oic acid  The carboxyl carbon atom is C1 20.1 Naming Carboxylic Acids and Nitriles

5.  Compounds with –CO 2 H bonded to a ring are named using the suffix -carboxylic acid  The CO 2 H carbon is not itself numbered in this system  Use common names for formic acid (HCOOH) and acetic acid (CH 3 COOH) – see Table 20.1 Alternative Names

6.  Closely related to carboxylic acids named by adding - nitrile as a suffix to the alkane name, with the nitrile carbon numbered C1  Complex nitriles are acids; named as derivatives of carboxylic acids.  Replace -ic acid or -oic acid ending with -onitrile Nitriles, RCN

7.  Carboxyl carbon sp 2 hybridized: carboxylic acid groups are planar with C–C=O and O=C–O bond angles of approximately 120°  Carboxylic acids form hydrogen bonds, existing as cyclic dimers held together by two hydrogen bonds  Strong hydrogen bonding causes much higher boiling points than the corresponding alcohols 20.2 Structure and Properties of Carboxylic Acids

8.  Carboxylic acids are proton donors toward weak and strong bases, producing metal carboxylate salts, RCO 2  + M  Carboxylic acids with more than six carbons are only slightly soluble in water, but their conjugate base salts are water-soluble Dissociation of Carboxylic Acids

9.  Carboxylic acids transfer a proton to water to give H 3 O + and carboxylate anions, RCO 2 , but H 3 O + is a much stronger acid  The acidity constant, K a,, is about 10 -5 for a typical carboxylic acid (pK a ~ 5) Acidity Constant and pK a

10.  Electronegative substituents promote formation of the carboxylate ion Substituent Effects on Acidity

11.  Fluoroacetic, chloroacetic, bromoacetic, and iodoacetic acids are stronger acids than acetic acid  Multiple electronegative substituents have synergistic effects on acidity Inductive Effects on Acidity

12.  If pK a of given acid and the pH of the medium are known, % of dissociated and undissociated forms can be calculated using the Henderson- Hasselbalch eqn 20.3 Biological Acids and the Henderson-Hasselbalch Equation Henderson-Hasselbalch equation

13. 20.4 Substituent Effects on Acidity

14.  An electron-withdrawing group (-NO 2 ) increases acidity by stabilizing the carboxylate anion, and an electron-donating (activating) group (OCH 3 ) decreases acidity by destabilizing the carboxylate anion  We can use relative pK a ’s as a calibration for effects on relative free energies of reactions with the same substituents Aromatic Substituent Effects

15.  Oxidation of a substituted alkylbenzene with KMnO 4 or Na 2 Cr 2 O 7 gives a substituted benzoic acid (see Section 16.9)  1° and 2° alkyl groups can be oxidized, but tertiary groups are not 20.5 Preparing Carboxylic Acids

16.  Oxidative cleavage of an alkene with KMnO 4 gives a carboxylic acid if the alkene has at least one vinylic hydrogen (see Section 7.9) From Alkenes

17.  Oxidation of a primary alcohol or an aldehyde with CrO 3 in aqueous acid From Alcohols

18.  Hot acid or base yields carboxylic acids  Conversion of an alkyl halide to a nitrile (with cyanide ion) followed by hydrolysis produces a carboxylic acid with one more carbon (RBr  RC  N  RCO 2 H)  Best with primary halides because elimination reactions occur with secondary or tertiary alkyl halides Hydrolysis of Nitriles

19.  Grignard reagents react with dry CO 2 to yield a metal carboxylate  Limited to alkyl halides that can form Grignard reagents  The organomagnesium halide adds to C=O of carbon dioxide  Protonation by addition of aqueous HCl in a separate step gives the free carboxylic acid Carboxylation of Grignard Reagents

20.  Carboxylic acids transfer a proton to a base to give anions, which are good nucleophiles in S N 2 reactions  Like ketones, carboxylic acids undergo addition of nucleophiles to the carbonyl group  In addition, carboxylic acids undergo other reactions characteristic of neither alcohols nor ketones 20.6 Reactions of Carboxylic Acids: An Overview

21.  Nitriles and carboxylic acids both have a carbon atom with three bonds to an electronegative atom, and contain a  bond  Both both are electrophiles 20.7 Chemistry of Nitriles

22.  Reaction of primary amides RCONH 2 with SOCl 2 or POCl 3 (or other dehydrating agents)  Not limited by steric hindrance or side reactions (as is the reaction of alkyl halides with NaCN) Preparation of Nitriles by Dehydration

23.  Nucleophilic amide oxygen atom attacks SOCl 2 followed by deprotonation and elimination Mechanism of Dehydration of Amides

24.  RC  N is strongly polarized and with an electrophilic carbon atom  Attacked by nucleophiles to yield sp 2 -hybridized imine anions Reactions of Nitriles

25.  Hydrolyzed in with acid or base catalysis to a carboxylic acid and ammonia Hydrolysis: Conversion of Nitriles into Carboxylic Acids

26.  Nucleophilic addition of hydroxide to C  N bond  Protonation gives a hydroxy imine, which tautomerizes to an amide  A second hydroxide adds to the amide carbonyl group and loss of a proton gives a dianion  Expulsion of NH 2  gives the carboxylate Mechanism of Hydrolysis of Nitriles

27. Reduction of a nitrile with LiAlH 4 gives a primary amine  Nucleophilic addition of hydride ion to the polar C  N bond, yielding an imine anion  The C=N bond undergoes a second nucleophilic addition of hydride to give a dianion, which is protonated by water Reduction: Conversion of Nitriles into Amines

28.  Grignard reagents add to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone Reaction of Nitriles with Organometallic Reagents

29. Infrared Spectroscopy  O–H bond of the carboxyl group gives a very broad absorption 2500 to 3300 cm  1  C=O bond absorbs sharply between 1710 and 1760 cm  1  Free carboxyl groups absorb at 1760 cm  1  Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm  1 20.8 Spectroscopy of Carboxylic Acids and Nitriles

30.  Nitriles show an intense C  N bond absorption near 2250 cm  1 for saturated compounds and 2230 cm  1 for aromatic and conjugated molecules  This is highly diagnostic for nitriles IR of Nitriles

31.  Carboxyl 13 COOH signals are at  165 to  185  Aromatic and ,  -unsaturated acids are near  165 and saturated aliphatic acids are near  185  13 C  N signal  115 to  130 Nuclear Magnetic Resonance Spectroscopy

32.  The acidic –CO 2 H proton is a singlet near  12  When D 2 O is added to the sample the –CO 2 H proton is replaced by D causing the absorption to disappear from the NMR spectrum Proton NMR

33. Examine the 3 compounds below. Place them in order with respect to increasing acidity. Fluoroacetic acid, 3-fluoroacetic acid, iodoacetic acid Let’s Work a Problem

34. Answer The strongest acid has the the MOST electronegative atom immediately adjacent to the carboxylic acid group (FCH 2 CO 2 H), then next is the compound with an electronegative atom, that may not be the strongest, but is also adjacent to the carboxylic acid (ICH 2 CO 2 H). Lastly is the molecule with an electronegative atom; however, it is separated from the carboxylic acid portion via a methylene group (FCH 2 CH 2 CO 2 H)