1 / 68

Functional Derivatives of Carboxylic Acids

Functional Derivatives of Carboxylic Acids. Chapter 18. Carboxyl Derivatives. In this chapter, we study five classes of organic compounds. under the structural formula of each is a drawing to help you see its relationship to the carboxyl group. 18.1 A. Structure: Acid Chlorides.

briar
Download Presentation

Functional Derivatives of Carboxylic Acids

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Functional Derivatives of Carboxylic Acids Chapter 18

  2. Carboxyl Derivatives • In this chapter, we study five classes of organic compounds. • under the structural formula of each is a drawing to help you see its relationship to the carboxyl group.

  3. 18.1 A.Structure: Acid Chlorides • The functional group of an acid halide is an acyl group bonded to a halogen. • the most common are the acid chlorides. • to name, change the suffix -ic acidto -yl halide.

  4. Sulfonyl Chlorides • replacement of -OH in a sulfonic acid by -Cl gives a sulfonyl chloride.

  5. B. Acid Anhydrides • The functional group of an acid anhydride has two acyl groups bonded to an oxygen atom. • the anhydride may be symmetrical (two identical acyl groups) or mixed (two different acyl groups). • to name, replace acid of the parent acid by anhydride. ethanoic anhydride

  6. Succinic Phthalic M aleic anhydride anhydride anhydride Acid Anhydrides • Cyclic anhydrides are named from the dicarboxylic acids from which they are derived. O O O O O O O O O

  7. - - O - P - O - P - O H O - P - O - P - O H - - O O O H O H Diphosphoric acid Diphosphate ion (Pyrophosphoric acid) (Pyrophosphate ion) - - O - P - O - P - O - P - O H O - P - O - P - O - P - O H - - - - - - O O O O O O Phosphoric Anhydrides • A phosphoric anhydride contains two phosphoryl groups bonded to an oxygen atom. O O O O O O O O O O Triphosphoric acid Triphosphate ion

  8. C. 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. • change the suffix -ic acid to –ate.

  9. Esters • Cyclic esters are called lactones. • name the parent carboxylic acid, drop the suffix -ic acid and add –olactone. 4-hydroxybutanoic acid lactone

  10. Esters of Phosphoric Acid • 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 phosphoric esters, it is common to name the organic molecule and then indicate the presence of the phosphoric ester by the word phosphate or the prefix phospho-.

  11. D. Amides • The functional group of an amide is an acyl group bonded to a nitrogen atom. • IUPAC: drop -oic acidfrom the name of the parent acid and add –amide. • if the amide nitrogen is bonded to an alkyl or aryl group, name the group and show its location on nitrogen by N-.

  12. Amides • Cyclic amides are called lactams. • name the parent carboxylic acid, drop the suffix -ic acid and add –lactam.

  13. Penicillins • the penicillins are a family of -lactam antibiotics.

  14. Cephalosporins • the cephalosporins are also -lactam antibiotics.

  15. Imides • The functional group of an imide is two acyl groups bonded to nitrogen. • both succinimide and phthalimide are cyclic imides.

  16. E. Nitriles • The functional group of a nitrile is a cyano group. • IUPAC names: name as an alkanenitrile.. • common names: drop the -ic acidand add -onitrile

  17. Naming Summary • Open chain Cyclic • pentanoic acid cyclopentanecarboxylic acid • pentanoyl chloride cyclopentanecarbonyl chloride • pentanoic anhydride cyclopentanecarboxylic acid • ethanoic methanoic anhydride butandioic anhydride • ethyl pentanoate ethyl cyclopentanecarboxylate • pentanamide cyclopentanecarboxamide • pentanenitrile cyclopentanecarbonitrile 4-aminopentanoic acid lactam 4-hydroxypentanoic acid lactone

  18. 18.2 Acidity of N-H bonds • Amides are comparable in acidity to alcohols. • water-insoluble amides do not react with NaOH or other alkali metal hydroxides to form water-soluble salts. • Sulfonamides and imides are more acidic than amides.

  19. Acidity of N-H bonds • Imides are more acidic than amides because. 1. the electron-withdrawing inductive of the two adjacent C=O groups weakens the N-H bond, and 2. the imide anion is stabilized by resonance delocalization of the negative charge.

  20. - + N H N a O H N N a H O 2 pK 8.3 pK 15.7 a a (stronger (stronger (weaker (weaker acid) base) base) acid) Acidity of N-H • imides such as phthalimide readily dissolve in aqueous NaOH as water-soluble salts. O O + + O O

  21. 18.3 Characteristic Reactions • Nucleophilic acyl substitution:an addition-elimination sequence resulting in substitution of one nucleophile for another.

  22. Characteristic Reactions • 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.

  23. 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.

  24. 18.4 A. Reaction with H2O - 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.

  25. B. Reaction with H2O - 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.

  26. C H - C - O - C - C H C H - C - O - C - C H C H - C - O - C - C H H - O - H 3 3 3 3 3 3 O - H O - H T e t r a h e d r a l c a r b o n y l a d d i t i o n i n t e r m e d i a t e Reaction with H2O - Anhydrides • Step 1: addition of H2O to give a TCAI. • Step 2: protonation followed collapse of the TCAI. H + H O H O O O O O + + + O H O H H H H H

  27. C. Reaction with H2O - Esters • Esters are hydrolyzed only slowly, even in boiling water. • hydrolysis becomes more rapid if they are heated with either aqueous acid or base. • Hydrolysis in aqueous acid is the reverse of Fischer esterification. • the role of the acid catalyst is to protonate the carbonyl oxygen and increase its electrophilic character toward attack by water (a weak nucleophile) to form a tetrahedral carbonyl addition intermediate. • collapse of this intermediate gives the carboxylic acid and alcohol.

  28. Reaction with H2O - Esters • Acid-catalyzed ester hydrolysis.

  29. Reaction with H2O - Esters • Hydrolysis of an esters 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. • hydrolysis of an ester in aqueous base involves formation of a tetrahedral carbonyl addition intermediate followed by its collapse and proton transfer.

  30. Reaction with H2O - Esters • Step 1: attack of hydroxide ion (a nucleophile) on the carbonyl carbon (an electrophile) • Step 2: collapse of the TCAI. • Step 3: proton transfer to the alkoxide ion; this step is irreversible and drives saponification to completion.

  31. D. Reaction with H2O - Amides • Hydrolysis of an amide in aqueous acid requires 1 mole of acid per mole of amide. • reaction is driven to completion by the acid-base reaction between the amine or ammonia and the acid.

  32. Reaction with H2O - Amides • Hydrolysis of an amide in aqueous base requires 1 mole of base per mole of amide. • reaction is driven to completion by the irreversible formation of the carboxylate sale.

  33. Reaction with H2O - Amides • Step1: protonation of the carbonyl oxygen gives a resonance-stabilized cation intermediate.

  34. Reaction with H2O - Amides • Step 2: addition of water (a nucleophile) to the carbonyl carbon (an electrophile) followed by proton transfer gives a TCAI. • Step 3: collapse of the TCAI and proton transfer.

  35. O H + H H O R - C R - C N H R - C - N H 2 2 A n i m i d i c a c i d A n a m i d e ( e n o l o f a n a m i d e ) E. Reaction with H2O - Nitriles • The cyano group is hydrolyzed in aqueous acid to a carboxyl group and ammonium ion. • protonation of the cyano nitrogen gives a cation that reacts with water to give an imidic acid • keto-enol tautomerism gives the amide. O N +

  36. Reaction with H2O - Nitriles • hydrolysis of a cyano group in aqueous base gives a carboxylic anion and ammonia; acidification converts the carboxylic anion to the carboxylic acid.

  37. Reaction with H2O - Nitriles • hydrolysis of nitriles is a valuable route to carboxylic acids.

  38. 18.5 A.Reaction with Alcohols • Acid halides react with alcohols to give esters. • acid halides are so reactive toward even weak nucleophiles such as alcohols that no catalyst is necessary. • where the alcohol or resulting ester is sensitive to HCl, reaction is carried out in the presence of a 3° amine to neutralize the acid.

  39. Reaction with Alcohols • sulfonic acid esters are prepared by the reaction of an alkane- or arenesulfonyl chloride (Section 18.1A) with an alcohol or phenol. • the key point here is that OH- (a poor leaving group) is transformed into a sulfonic ester (a good leaving group) with retention of configuration at the chiral center.

  40. C H C O C C H H O C H C H C H C O C H C H C H C O H 3 3 2 3 3 2 3 3 A c e t i c a n h y d r i d e E t h a n o l E t h y l a c e t a t e A c e t i c a c i d B. Reaction with Alcohols • Acid anhydrides react with alcohols to give one mole of ester and one mole of carboxylic acid. • cyclic anhydrides react with alcohols to give one ester group and one carboxyl group. O O O O + +

  41. C O O H O H C H C O C C H 3 3 A cetic 2-Hydroxybenzoic anhydride acid C O O H (Salicylic acid) C H 3 C H C O H 3 Acetylsalicylic acid (Aspirin) Reaction with Alcohols • aspirin is synthesized by treating salicylic acid with acetic anhydride. O O + O O + O Acetic acid

  42. H C l H O O C H 3 Methyl propenoate 1-Butanol (Methyl acrylate) (bp 117°C) (bp 81°C) C H O H 3 Butyl propenoate Methanol (Butyl acrylate) (bp 65°C) (bp 147°C) C. Reaction with Alcohols • Esters react with alcohols in the presence of an acid catalyst in an equilibrium reaction called transesterification. O + O O + D. Amides are the least reactive acid derivatives

  43. 18.6 A.Reaction with Ammonia, etc. • 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.

  44. B. Reaction with Ammonia, etc. • Acid anhydrides react with ammonia, and 1° and 2° amines to form amides. • 2 moles of ammonia or amine are required.

  45. C. Reaction with Ammonia, etc. • Esters react with ammonia, and 1° and 2° amines to form amides. • esters are less reactive than either acid halides or acid anhydrides. D. Amides do not react with ammonia, or 1° or 2° amines.

  46. POCl3 N C N H 2 P h P h D. Reaction of Amides • An unsubstituted amide can be converted into a nitrile using POCl3. • POCl3 is a dehydrating agent that removes water from the amide. O + heat 2-Phenylbutanamide 2-Phenylbutanenitrile

  47. 18.7 Acid Chlorides with Salts • Acid chlorides react with salts of carboxylic acids to give anhydrides. • most commonly used are sodium or potassium salts.

  48. 18.8 Interconversions, Fig. 18.1

  49. 18.9 A.Reaction with Grignard Reagents • treating a formic ester with 2 moles of Grignard reagent followed by hydrolysis in aqueous acid gives a 2° alcohol.

  50. Reaction with Grignard Reagents • treating an ester other than formic with a Grignard reagent followed by hydrolysis in aqueous acid gives a 3° alcohol.

More Related