Carboxylic Acids. The Importance of Carboxylic Acids (RCO 2 H)

Transcription

1 Carboxylic Acids The Importance of Carboxylic Acids (RCO 2 H) 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 Carboxylic acids present in many industrial processes and most biological processes They are the starting materials from which other acyl derivatives are made 2 1

2 Naming Carboxylic Acids 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 3 Alternative Names 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

3 Structure and Properties of Carboxylic Acids 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 5 Dissociation of Carboxylic Acids 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 6 3

4 Acidity Constant and pk a 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) 7 Substituent Effects on Acidity Electronegative substituents promote formation of the carboxylate ion 8 4

5 Inductive Effects on Acidity Fluoroacetic, chloroacetic, bromoacetic, and iodoacetic acids are stronger acids than acetic acid Multiple electronegative substituents have synergistic effects on acidity 9 Preparation of Carboxylic Acids 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 10 5

6 From Alkenes 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) 11 From Alcohols Oxidation of a primary alcohol or an aldehyde with CrO 3 in aqueous acid 12 6

7 Reactions of Carboxylic Acids: An Overview 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 13 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 7

8 Carboxylic Compounds Acyl group bonded to X, an electronegative atom or leaving group Includes: X = halide (acid halides), acyloxy (anhydrides), alkoxy (esters), amine (amides) Nucleophilic acyl substitution 15 Naming Carboxylic Acid Derivatives Acid Halides, RCOX Derived from the carboxylic acid name by replacing the -ic acid ending with -yl or the -carboxylic acid ending with carbonyl and specifying the halide 16 8

9 Naming Acid Anhydrides, RCO 2 COR' If symmetrical replace acid with anhydride based on the related carboxylic acid From substituted monocarboxylic acids: use bisahead of the acid name Unsymmetrical anhydrides cite the two acids alphabetically 17 Naming Amides, RCONH 2 With unsubstituted NH 2 group. replace -oic acid or -ic acid with -amide, or by replacing the -carboxylic acid ending with carboxamide If the N is further substituted, identify the substituent groups (preceded by N ) and then the parent amide 18 9

10 Naming Esters, RCO 2 R Name R and then, after a space, the carboxylic acid (RCOOH), with the -ic acid ending replaced by -ate 19 Nucleophilic Acyl Substitution Carboxylic acid derivatives have an acyl carbon bonded to a group Y that can leave A tetrahedral intermediate is formed and the leaving group is expelled to generate a new carbonyl compound, leading to substitution 20 10

11 Relative Reactivity of Carboxylic Acid Derivatives Nucleophiles react more readily with unhindered carbonyl groups More electrophilic carbonyl groups are more reactive to addition (acyl halides are most reactive, amides are least) The intermediate with the best leaving group decomposes fastest 21 General Reactions of Carboxylic Acid Derivatives water carboxylic acid alcohols esters ammonia or an amine an amide hydride source an aldehyde or an alcohol Grignard reagent a ketone or an alcohol 22 11

12 Conversion of Carboxylic Acids into Acid Chlorides Reaction with thionyl chloride, SOCl 2 23 Conversion of Carboxylic Acids into Acid Anhydrides Acid anhydrides can be derived from two molecules of carboxylic acid by strong heating to remove water 24 12

13 Conversion of Carboxylic Acids into Esters Methods include reaction of a carboxylate anion with a primary alkyl halide 25 Fischer Esterification Heating a carboxylic acid in an alcohol solvent containing a small amount of strong acid produces an ester from the alcohol and acid 26 13

14 Chemistry of Acid Halides Acid chlorides are prepared from carboxylic acids by reaction with SOCl 2 Reaction of a carboxylic acid with PBr 3 yields the acid bromide 27 Hydrolysis: Conversion of Acid Halides into Acids Acid chlorides react with water to yield carboxylic acids HCl is generated during the hydrolysis: a base is added to remove the HCl 28 14

15 Conversion of Acid Halides to Esters Esters are produced in the reaction of acid chlorides with alcohols in the presence of pyridine or NaOH. This is called Alcoholysis The reaction is better with less steric bulk 29 Aminolysis: Conversion of Acid Halides into Amides Amides result from the reaction of acid chlorides with NH 3, primary (RNH 2 ) and secondary amines (R 2 NH) The reaction with tertiary amines (R 3 N) gives an unstable species that cannot be isolated HCl is neutralized by the amine or an added base 30 15

16 Reaction of Acid Chlorides with Organometallic Reagents Grignard reagents react with acid chlorides to yield tertiary alcohols in which two of the substituents are the same 31 Formation of Ketones from Acid Chlorides Reaction of an acid chloride with a lithium diorganocopper (Gilman) reagent, Li + R 2 Cu Addition produces an acyl diorganocopper intermediate, followed by loss of R Cu and formation of the ketone 32 16

17 Chemistry of Acid Anhydrides Prepared by nucleophilic acyl substitution of a carboxylate with an acid chloride 33 Reactions of Acid Anhydrides Similar to acid chlorides in reactivity 34 17

18 Acetylation Acetic anhydride forms acetate esters from alcohols and N-substituted acetamides from amines 35 Chemistry of Esters Many esters are pleasant-smelling liquids: fragrant odors of fruits and flowers Also present in fats and vegetable oils 36 18

19 Preparation of Esters Esters are usually prepared from carboxylic acids 37 Reactions of Esters Less reactive toward nucleophiles than are acid chlorides or anhydrides Cyclic esters are called lactones and react similarly to acyclic esters 38 19

20 Hydrolysis: Conversion of Esters into Carboxylic Acids An ester is hydrolyzed by aqueous base or aqueous acid to yield a carboxylic acid plus an alcohol 39 Reduction: Conversion of Esters into Alcohols Reaction with LiAlH 4 yields primary alcohols 40 20

21 Reaction of Esters with Grignard Reagents React with 2 equivalents of a Grignard reagent to yield a tertiary alcohol Chemistry of Amides Amides are abundant in all living organisms proteins, nucleic acids, and other pharmaceuticals have amid functional groups 42 21

22 Preparation of Amides Prepared by reaction of an acid chloride with ammonia, monosubstituted amines, or disubstituted amines 43 Reduction: Conversion of Amides into Amines Reduced by LiAlH 4 to an amine rather than an alcohol Converts C=O CH

23 Nitriles, RCN 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 named as derivatives of carboxylic acids. Replace -ic acid or -oic acid ending with -onitrile 45 Chemistry of Nitriles Nitriles and carboxylic acids both have a carbon atom with three bonds to an electronegative atom, and contain a bond Both both are electrophiles 46 23

24 Reactions of Nitriles RC N is strongly polarized and with an electrophilic carbon atom Attacked by nucleophiles to yield sp 2 -hybridized imine anions 47 Hydrolysis: Conversion of Nitriles into Carboxylic Acids Hydrolyzed in with acid or base catalysis to a carboxylic acid and ammonia or an amine 48 24

25 Hydrolysis of Nitriles 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 49 Reduction: Conversion of Nitriles into Amines Reduction of a nitrile with LiAlH 4 gives a primary amine Nucleophilic addition of hydride ion to the polar C N bond, yieldis an imine anion The C=N bond undergoes a second nucleophilic addition of hydride to give a dianion, which is protonated by water 50 25

26 Reaction of Nitriles with Organometallic Reagents Grignard reagents add to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone 51 Amines Organic Bases 26

27 Amines Organic Nitrogen Compounds Organic derivatives of ammonia, NH 3, Nitrogen atom with a lone pair of electrons, making amines both basic and nucleophilic Occur in plants and animals 53 Naming Amines Alkyl-substituted (alkylamines) or aryl-substituted (arylamines) Classified: 1 (RNH 2 ), methyl (CH 3 NH 2 ), 2 (R 2 NH), 3 (R 3 N) Quaternary Ammonium Ions: A nitrogen atom with four attached groups is positively charged

28 Simple Amines For simple amines, the suffix -amine is added to the name of the alkyl substituent The suffix -amine can be used in place of the final -e in the name of the parent compound 55 Amines With More Than One Functional Group Consider the NH 2 as an amino substituent on the parent molecule Multiple Alkyl Groups: Symmetrical secondary and tertiary amines are named by adding the prefix di- or tri- to the alkyl group 56 28

29 Multiple, Different Alkyl Groups Named as N-substituted primary amines Largest alkyl group is the parent name, and other alkyl groups are considered N-substituents If the nitrogen atom occurs as part of a ring, the compound is designated as being heterocyclic amines. Each ring system has its own parent name. 57 Amines Form H-Bonds Amines with fewer than five carbons are water-soluble Primary and secondary amines form hydrogen bonds, increasing their boiling points Basicity of Amines: The lone pair of electrons on nitrogen makes amines basic and nucleophilic They react with acids to form acid base salts and they react with electrophiles 58 29

30 S N 2 Reactions of Alkyl Halides Ammonia and other amines are good nucleophiles 59 Uncontrolled Multiple Alkylation Primary, secondary, and tertiary amines all have similar reactivity, the initially formed monoalkylated substance undergoes further reaction to yield a mixture of products 60 30

31 Reductive Amination of Aldehydes and Ketones Treatment of an aldehyde or ketone with ammonia or an amine in the presence of a reducing agent 61 Reductive Amination Is Versatile Ammonia, primary amines, and secondary amines yield primary, secondary, and tertiary amines, respectively 62 31

32 Hofmann Rearrangements Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement rearrangement 63 Hofmann Elimination Converts amines into alkenes NH 2 is very a poor leaving group so it converted to an alkylammonium ion, which is a good leaving group Silver Oxide Is Used for the Elimination Step: Exchanges hydroxide ion for iodide ion in the quaternary ammonium salt, thus providing the base necessary to cause elimination 64 32

33 Diazonium Salts: The Sandmeyer Reaction Primary arylamines react with HNO 2, yielding stable arenediazonium salts The N 2 group can be replaced by a nucleophile 65 Diazonium Coupling Reactions Arenediazonium salts undergo a coupling reaction with activated aromatic rings, such as phenols and arylamines, to yield brightly colored azo compounds, Ar N=N Ar 66 33

34 Azo Dyes Azo-coupled products have extended conjugation that lead to low energy electronic transitions that occur in visible light (dyes) 67 34