Organic Chemistry II Ch 21 Klein

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Organic Chemistry II Ch 21 Klein

  1. 1. 21.1 Introduction Carboxylic Acids<br />Carboxylic acids are abundant in nature and in pharmaceuticals. <br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-1<br />
  2. 2. 21.1 Introduction Carboxylic Acids<br />The US produces over 2.5 million tons of acetic acid per year, which is primarily used to produce vinyl acetate.<br />Vinyl acetate is used in paints and adhesives.<br />Carboxylic acid derivatives, such as vinyl acetate, are very common, and they play a central role in organic chemistry.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-2<br />
  3. 3. 21.2 Nomenclature of Carboxylic Acids<br />Monocarboxylic acids are named with the suffix “oic acid.”<br />The carbon of the carboxylic acid moiety is assigned the locant position 1.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-3<br />
  4. 4. 21.2 Nomenclature of Carboxylic Acids<br />When the carboxylic acid group is attached to a ring, it is named as an alkane carboxylic acid.<br />There are also many common names for carboxylic acids.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-4<br />
  5. 5. 21.2 Nomenclature of Carboxylic Acids<br />Dicarboxylic acids are named with the suffix “dioic acid.”<br />There are also many common names for dicarboxylic acids:<br />Practice with CONCEPTUAL CHECKPOINTs 12.1 through 12.3.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-5<br />
  6. 6. 21.3 Structure and Properties of Carboxylic Acids<br />The carbon atom of the carboxylic acid has a trigonal planar geometry. WHY?<br />The acid moiety is capable of strong hydrogen (H­) bonding including H-bonding between acid pairs.<br />As a result, carboxylic acids generally have high boiling points.<br />Consider the BPs of acetic acid (118 °C) and isopropanol (82 °C).<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-6<br />
  7. 7. 21.3 Structure and Properties of Carboxylic Acids<br />Carboxylate ions end in the suffix “oate.”<br />Compounds that end in the suffix “oate” are often found in food ingredient lists as preservatives.<br />NaOH is a strong base, so it is capable of reacting ≈100% with a carboxylic acid.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-7<br />
  8. 8. 21.3 Structure and Properties of Carboxylic Acids<br />In water, the equilibrium generally favors the acid .<br />pKa values mostly range between 4 and 5. What is pKa?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-8<br />
  9. 9. 21.3 Structure and Properties of Carboxylic Acids<br />How does the pKa value for a carboxylic acid compare to a strong acid like HCl, or a very weak acid like ethanol?<br />H–Cl<br />pKa= -7<br />How can induction and resonance be used to explain the acidity of a carboxylic acid?<br />Practice with CONCEPTUAL CHECKPOINTs 21.4 through 21.7.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-9<br />
  10. 10. 21.3 Structure and Properties of Carboxylic Acids<br />Let’s examine the equilibrium between the carboxylic acid and the carboxylate at physiological pH (7.3).<br />The acid and the conjugate base make a buffer. HOW?<br />Recall that the Henderson-Hasselbalch equation can be used to calculate the pH of a buffer:<br />Assuming the pKa is 4.3, calculate the ratio of carboxylate/acid.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-10<br />
  11. 11. 21.3 Structure and Properties of Carboxylic Acids<br />Many biomolecules exhibit carboxylic acid moieties.<br />Biomolecules such as pyruvic acid exist primarily as the carboxylate under physiological conditions.<br />Practice with CONCEPTUAL CHECKPOINT 21.8.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-11<br />
  12. 12. 21.3 Structure and Properties of Carboxylic Acids<br />Electron withdrawing substituents have a great effect on acidity.<br />WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-12<br />
  13. 13. 21.3 Structure and Properties of Carboxylic Acids<br />Electron withdrawing substituents affect benzoic acid as well.<br />Practice with CONCEPTUAL CHECKPOINT 21.9.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-13<br />
  14. 14. 21.4 Preparation of Carboxylic Acids<br />In earlier chapters, we already learned some methods to synthesize carboxylic acids.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-14<br />
  15. 15. 21.4 Preparation of Carboxylic Acids<br />In earlier chapters, we already learned some methods to synthesize carboxylic acids.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-15<br />
  16. 16. 21.4 Preparation of Carboxylic Acids<br />Let’s examine two more ways to make carboxylic acids:<br />The hydrolysis of a nitrile can produce a carboxylic acid.<br />The mechanism will be discussed later.<br />Carboxylic acids can be made from alkyl halides using a two-step process.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-16<br />
  17. 17. 21.4 Preparation of Carboxylic Acids<br />Let’s examine two more ways to make carboxylic acids:<br />Carboxylation of a Grignard reaction can be achieved using CO2.<br />The Grignard reagent and the H3O+ cannot be added together. WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-17<br />
  18. 18. 21.4 Preparation of Carboxylic Acids<br />This gives us a second method to convert an alkyl halide into a carboxylic acid:<br />Practice with CONCEPTUAL CHECKPOINT 12.10.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-18<br />
  19. 19. 21.5 Reactions of Carboxylic Acids<br />LiAlH4 (LAH) is a strong reducing agent that can convert an acid to a primary alcohol:<br />The LAH acts as a base first.<br />Then, an aldehyde is produced.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-19<br />
  20. 20. 21.5 Reactions of Carboxylic Acids<br />LiAlH4 (LAH) is a strong reducing agent that can convert an acid to a primary alcohol:<br />The aldehyde is further reduced to the alcohol.<br />Can the reduction be stopped at the aldehyde?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-20<br />
  21. 21. 21.5 Reactions of Carboxylic Acids<br />The milder borane reagent can also be used to promote the reduction.<br />Reduction with borane is selective compared to LAH reduction.<br />Practice with CONCEPTUAL CHECKPOINT 21.11.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-21<br />
  22. 22. 21.6 Introduction to Carboxylic Acid Derivatives<br />The reduction of acids with LAH or borane result in a decrease in the oxidation number for carbon. HOW?<br />There are also many reactions where carboxylic acids don’t change their oxidation state.<br />What criteria must Z fulfill so that there is no change in the oxidation state?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-22<br />
  23. 23. 21.6 Introduction to Carboxylic Acid Derivatives<br />When Z is a heteroatom, the compound is called a carboxylic acid derivative.<br />Because it has the same oxidation state, a nitrile is also an acid derivative despite not having a carbonyl group.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-23<br />
  24. 24. 21.6 Introduction to Carboxylic Acid Derivatives<br />Acid halides and anhydrides are relatively unstable, so they are not common in nature; we will discuss their instability in detail later in this chapter.<br />Some naturally occurring esters are known to have pleasant odors:<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-24<br />
  25. 25. 21.6 Introduction to Carboxylic Acid Derivatives<br />Amides are VERY common in nature.<br />What type of molecule in nature includes amide linkages?<br />Many other compounds feature amides, including some natural sedatives like melatonin.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-25<br />
  26. 26. 21.6 Introduction to Carboxylic Acid Derivatives<br />To name an acid halide, replace “ic acid” with “yl halide.”<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-26<br />
  27. 27. 21.6 Introduction to Carboxylic Acid Derivatives<br />Alternatively, the suffix, “carboxylic acid” can be replaced with “carbonyl halide.”<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-27<br />
  28. 28. 21.6 Introduction to Carboxylic Acid Derivatives<br />Acid anhydrides are named by replacing “acid” with “anhydride.”<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-28<br />
  29. 29. 21.6 Introduction to Carboxylic Acid Derivatives<br />Asymmetric acid anhydrides are named by listing the acids alphabetically and adding the word anhydride.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-29<br />
  30. 30. 21.6 Introduction to Carboxylic Acid Derivatives<br />Esters are named by naming the alkyl group attached to the oxygen followed by the carboxylic acid’s name with the suffix “ate.”<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-30<br />
  31. 31. 21.6 Introduction to Carboxylic Acid Derivatives<br />Amides are named by replacing the suffix “ic acid” or “oic acid” with “amide.”<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-31<br />
  32. 32. 21.6 Introduction to Carboxylic Acid Derivatives<br />If the nitrogen atom of the amide group bears alkyl substituents, their names are placed at the beginning of the name with N as their locant.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-32<br />
  33. 33. 21.6 Introduction to Carboxylic Acid Derivatives<br />Nitriles are named by replacing the suffix “ic acid” or “oic acid” with “onitrile.”<br />Practice with CONCEPTUAL CHECKPOINTs 21.12 and 21.13.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-33<br />
  34. 34. 21.7 Reactivity of Carboxylic Acid Derivatives<br />In general, carboxylic acid derivatives are good electrophiles.<br />WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-34<br />
  35. 35. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Reactivity can be affected by <br />Induction<br />Resonance<br />Sterics<br />Quality of leaving group<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-35<br />
  36. 36. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Let’s examine the acid chloride:<br />The electronegative chlorine enhances the electrophilic character of the carbonyl. HOW?<br />There are 3 resonance contributors to the acid chloride: <br />The chlorine does not significantly donate electron density to the carbonyl. HOW does that affect its quality as an electrophile.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-36<br />
  37. 37. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Let’s examine the acid chloride:<br />Describe how the presence of the chloride affects the sterics of the nucleophilic attack on the carbonyl.<br />The chloride is a good leaving group, which also enhances its reactivity.<br />Considering all of the factors involved, the acid chloride is quite reactive.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-37<br />
  38. 38. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Amides are the least reactive acid derivative.<br />Examine the factors below to explain amide reactivity:<br />Induction<br />Resonance<br />Sterics<br />Quality of leaving group<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-38<br />
  39. 39. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Aldehydes and ketones are also electrophilic, but they do not undergo substitution.<br />WHY? Consider induction, resonance, sterics, and quality of leaving group.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-39<br />
  40. 40. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Nucleophilic acyl substitution is a two-step process.<br />Because C=O double bonds are quite stable, the “loss of leaving group” step should occur if a leaving group is present.<br />– H and –R do not qualify as leaving groups. WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-40<br />
  41. 41. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Let’s analyze a specific example:<br />The highest quality leaving group leaves the tetrahedral intermediate.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-41<br />
  42. 42. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Do NOT draw the acyl substitution with an SN2 mechanism.<br />Sometimes a proton transfer will be necessary in the mechanism:<br />Under acidic conditions, (–) charges rarely form. WHY?<br />Under basic conditions, (+) charges rarely form. WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-42<br />
  43. 43. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Under acidic conditions, (–) charges rarely form.<br />The first step will NOT be nucleophilic attack.<br />The electrophile and nucleophile are both low in energy.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-43<br />
  44. 44. 21.7 Reactivity of Carboxylic Acid Derivatives<br />H3O+ is unstable and drives the equilibrium forward by starting the reaction mechanism.<br />Now that the electrophile carries a (+) charge, it is much less stable (higher in energy). Complete the rest of the mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-44<br />
  45. 45. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Under basic conditions, (+) charges rarely form.<br />The OH– is the most unstable species in the reaction and drives the equilibrium forward.<br />Continue the rest of the mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-45<br />
  46. 46. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Neutral nucleophiles are generally less reactive, but they can still react if given enough time.<br />An intermediate with both (+) and (-) charges forms.<br />Intermediates with two (+) or two (–) charges are very unlikely to form. WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-46<br />
  47. 47. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Depending on reaction conditions, UP TO THREE proton transfers may be necessary in the mechanism:<br />Draw a complete mechanism for the reaction below.<br />Will the reaction be reversible? <br />What conditions could be employed to favor products?<br />Practice with SKILLBUILDER 21.1.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-47<br />
  48. 48. 21.7 Reactivity of Carboxylic Acid Derivatives<br />Give necessary reaction conditions and a complete mechanism for the reaction below.<br />Describe how conditions could be modified to favor the products as much as possible.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-48<br />
  49. 49. 21.8 Preparation and Reaction of Acid Chlorides<br />Acid chlorides have great synthetic utility. WHY?<br />An acid chloride may form when an acid is treated with SOCl2.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-49<br />
  50. 50. 21.8 Preparation and Reaction of Acid Chlorides<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-50<br />
  51. 51. 21.8 Preparation and Reaction of Acid Chlorides<br />The mechanism is more favored in the presence of a non-nucleophilic base like pyridine. WHY? <br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-51<br />
  52. 52. 21.8 Preparation and Reaction of Acid Chlorides: HYDROLYSIS<br />To avoid an acid chloride being converted into an acid, it must be protected from moisture.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-52<br />
  53. 53. 21.8 Preparation and Reaction of Acid Chlorides: ALCOHOLYSIS<br />Often acid chlorides are used to synthesize esters.<br />Give a complete mechanism showing the role of pyridine in the mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-53<br />
  54. 54. 21.8 Preparation and Reaction of Acid Chlorides: AMINOLYSIS<br />Often acid chlorides are used to synthesize amides.<br />Give a complete mechanism showing why TWO equivalents are used.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-54<br />
  55. 55. 21.8 Preparation and Reaction of Acid Chlorides<br />Acid chlorides can also be reduced using LAH:<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-55<br />
  56. 56. 21.8 Preparation and Reaction of Acid Chlorides<br />Acid chlorides can also be reduced using LAH:<br />The acid must be added after the LAH has given adequate time to react completely.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-56<br />
  57. 57. 21.8 Preparation and Reaction of Acid Chlorides<br />To stop the aldehyde from being reduced to the alcohol, a bulky reducing agent can be used.<br />HOW does lithium tri(t-butoxy) aluminum hydride allow the reduction to be stopped at the aldehyde?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-57<br />
  58. 58. 21.8 Preparation and Reaction of Acid Chlorides<br />Acid chlorides can also be attacked by Grignard nucleophiles:<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-58<br />
  59. 59. 21.8 Preparation and Reaction of Acid Chlorides<br />Two equivalents of the Grignard yield a 3° alcohol.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-59<br />
  60. 60. 21.8 Preparation and Reaction of Acid Chlorides<br />The Gilman reagent is another nucleophilic organometallic reagent that reacts readily with acid chlorides.<br />The C–Cu bond is less ionic than the C–Mg bond. WHY?<br />How does the ionic character of the bond affect the reactivity of the organometallic reagent?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-60<br />
  61. 61. 21.8 Preparation and Reaction of Acid Chlorides<br />Figure 21.9 illustrates the reactions of acid chlorides that we discussed.<br />Practice with CONCEPTUAL CHECKPOINTs 21.18 through 21.20.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-61<br />
  62. 62. 21.8 Preparation and Reaction of Acid Chlorides<br />Fill in necessary reagents for the reactions below.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-62<br />
  63. 63. 21.9 Preparation and Reactions of Acid Anhydrides<br />Acetic anhydride can be synthesized by heating 2 moles of acetic acid.<br />Why is so much heat needed to drive the equilibrium forward?<br />This process doesn’t work for most other acids because their structures cannot withstand such high temperatures.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-63<br />
  64. 64. 21.9 Preparation and Reactions of Acid Anhydrides<br />A more practical synthesis occurs when an acid chloride is treated with a carboxylate. <br />The –R groups attached to the anhydride do not have to be equivalent.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-64<br />
  65. 65. 21.9 Preparation and Reactions of Acid Anhydrides<br />Given that they both contain good quality leaving groups, how do you think the reactions of anhydrides compare to the reactions we already saw for chlorides?<br />Which has a better leaving group? WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-65<br />
  66. 66. 21.9 Preparation and Reactions of Acid Anhydrides<br />Figure 21.10 shows how anhydrides can undergo many reactions analogous to those of acid chlorides.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-66<br />
  67. 67. 21.9 Preparation and Reactions of Acid Anhydrides<br />A non-nucleophilic weak base such as pyridine is not necessary when acid anhydrides react with a nucleophile. WHY?<br />When a nucleophile reacts with an anhydride, there will be a carboxylic acid byproduct. WHY?<br />Why is it often a disadvantage to have such a byproduct in a reaction?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-67<br />
  68. 68. 21.9 Preparation and Reactions of Acid Anhydrides<br />Acetic anhydride is often used to acetylate an amine or an alcohol.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-68<br />
  69. 69. 21.9 Preparation and Reactions of Acid Anhydrides<br />Practice with CONCEPTUAL CHECKPOINT 21.21.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-69<br />
  70. 70. 21.10 Preparation of Esters<br />Fischer esterification combines a carboxylic acid and an alcohol using an acid catalyst.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-70<br />
  71. 71. 21.10 Preparation of Esters<br />Each step of the Fischer esterification mechanism is equilibrium.<br />Under acidic conditions, (–) charges are avoided.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-71<br />
  72. 72. 21.10 Preparation of Esters<br />The overall Fischer esterification reaction is an equilibrium process.<br />How might you use Le Châtelier’s principle to favor products?<br />How might you use Le Châtelier's principle to favor reactants?<br />Is there an entropy difference that might be exploited?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-72<br />
  73. 73. 21.10 Preparation of Esters<br />Esters can also be prepared by treating an acid chloride with an alcohol—see Section 21.8.<br />What is the role of pyridine?<br />Why doesn’t pyridine act as a nucleophile?<br />Practice with CONCEPTUAL CHECKPOINTs 21.22 and 21.23.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-73<br />
  74. 74. 21.11 Reactions of Esters<br />Esters can undergo hydrolysis in the presence of aqueous hydroxide (SAPONIFICATION).<br />Predict the last steps in the mechanism.<br />To produce a carboxylic acid, H3O+ must be added at the end. WHY?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-74<br />
  75. 75. 21.11 Reactions of Esters<br />SAPONIFICATION is an equilibrium process.<br />Analyze the reversibility of each step in the mechanism.<br />How might you use Le Châtelier’s principle to favor products?<br />How might you use Le Châtelier’s principle to favor reactants?<br />Is there an entropy difference that might be exploited?<br />Soap is made through the saponification of triglycerides. EXPLAIN HOW.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-75<br />
  76. 76. 21.11 Reactions of Esters<br />Ester hydrolysis can be catalyzed under acidic conditions.<br />The carbonyl of the ester is protonated, and then a water acts as a nucleophile attacking the carbonyl carbon.<br />Draw out the complete mechanism.<br />Show how regeneration of H3O+ makes it catalytic.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-76<br />
  77. 77. 21.11 Reactions of Esters<br />Esters can also undergo aminolysis.<br />The overall equilibrium favors the amide formation.<br />Because of enthalpy or entropy?<br />The synthetic utility is limited because the process is slow and because there are more efficient ways to synthesize amides.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-77<br />
  78. 78. 21.11 Reactions of Esters<br />Esters can be reduced using reagents such as LAH:<br />Two equivalents of reducing agent are required.<br />Two alcohols are produced.<br />Draw a reasonable mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-78<br />
  79. 79. 21.11 Reactions of Esters<br />LAHis a strong reducing agent, so a full reduction beyond the aldehyde to the alcohol cannot be avoided.<br />When performed at low temperature, reduction with DIBAH yields an aldehyde. HOW?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-79<br />
  80. 80. 21.11 Reactions of Esters<br />Esters can also react with Grignard reagents.<br />Two moles can be used to make a tertiary alcohol.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-80<br />
  81. 81. 21.11 Reactions of Esters<br />Esters can also react with Grignard reagents.<br />Two moles can be used to make a tertiary alcohol.<br />Practice with CONCEPTUAL CHECKPOINTs 21.24 and 21.25.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-81<br />
  82. 82. 21.11 Reactions of Esters<br />Give necessary reagents for the conversions below.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-82<br />
  83. 83. 21.12 Preparation and Reactions of Amides<br />Nylon is a polyamide.<br />Polyester is made similarly. HOW?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-83<br />
  84. 84. 21.12 Preparation and Reactions of Amides<br />Amides can be hydrolyzed with H3O+, but the process is slow and requires high temperature.<br />The mechanism is very similar to that for the hydrolysis of an ester.<br />Show a complete mechanism.<br />WHY is the process generally slow?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-84<br />
  85. 85. 21.12 Preparation and Reactions of Amides<br />Amides can be hydrolyzed with H3O+, but the process is slow and requires high temperature.<br />Should the equilibrium favor reactants or products? WHY?<br />Where does the NH4+ come from?<br />Amide hydrolysis can also be promoted with NaOH, although the process is very slow.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-85<br />
  86. 86. 21.12 Preparation and Reactions of Amides<br />LAH can reduce an amide to an amine.<br />The mechanism is quitedifferent from the others we have seen in this chapter.<br />When the H- attacks, which is the best leaving group?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-86<br />
  87. 87. 21.12 Preparation and Reactions of Amides<br />The iminium is reduced with a second equivalent of hydride.<br />Practice with CONCEPTUAL CHECKPOINTs<br /> 21.26 through 21.28.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-87<br />
  88. 88. 21.13 Preparation and Reactions of Nitriles<br />When a 1° or 2° alkyl halide is treated with a cyanide ion, the CN– acts as a nucleophile in an SN2 reaction.<br />Nitriles can also be made by dehydrating an amide using a variety of reagents including SOCl2.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-88<br />
  89. 89. 21.13 Preparation and Reactions of Nitriles<br />What base might you use?<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-89<br />
  90. 90. 21.13 Preparation and Reactions of Nitriles<br />An aqueous strong acid solution can be used to hydrolyze a nitrile.<br />In the mechanism, the nitrogen is protonated multiple times and water acts as a nucleophile.<br />Draw a complete mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-90<br />
  91. 91. 21.13 Preparation and Reactions of Nitriles<br />Basic hydrolysis of a nitrile can also be achieved.<br />Which group in the reaction acts as a nucleophile?<br />Which group acts to protonate the nitrogen?<br />Draw a complete mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-91<br />
  92. 92. 21.13 Preparation and Reactions of Nitriles<br />Nitriles can also react with Grignards.<br />After the nitrile is consumed, H3O+ is added to form an imine, which can be hydrolyzed with excess H3O+ (aq) to form a ketone. SHOW a mechanism.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-92<br />
  93. 93. 21.13 Preparation and Reactions of Nitriles<br />Similar to how carboxylic acids can be converted to alcohols using LAH (Section 21.5), nitriles can be converted to amines.<br />Practice with CONCEPTUAL CHECKPOINTs 21.29 through 21.31.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-93<br />
  94. 94. 21.14 Synthetic Strategies<br />When designing a synthesis, there are two general considerations that we make:<br />Is there a change in the CARBON SKELETON?<br />Is there a change in FUNCTIONAL GROUPS?<br />We have learned many new FUNCTIONAL GROUP TRANSFORMATIONsin this chapter.<br />Practice with SKILLBUILDER 21.2.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-94<br />
  95. 95. 21.14 Synthetic Strategies<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-95<br />
  96. 96. 21.14 Synthetic Strategies<br />Give necessary reagents for the conversion below. Multiple steps will be necessary.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-96<br />
  97. 97. 21.14 Synthetic Strategies<br />There are 2 categories of bond-forming reactions:<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-97<br />
  98. 98. 21.14 Synthetic Strategies<br />When forming new carbon-carbon bonds, it is critical to install functional groups in the proper location.<br />Give necessary reagents for the conversion below. More than one step will be necessary.<br />Practice with SKILLBUILDER 21.3.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-98<br />
  99. 99. 21.15 Spectroscopy of Carboxylic Acids and Their Derivatives<br />Recall that C=O stretching is a prominent peak in IR spectra.<br />Recall that conjugated carbonyl signals appear at lower wavenumbers (about 40 cm-1 less).<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-99<br />
  100. 100. 21.15 Spectroscopy of Carboxylic Acids and Their Derivatives<br />The O–H stretch of an acid gives a very broad peak (2500-3300 cm-1).<br />The CN triple bond stretch appears around 2200 cm-1.<br />Carbonyl 13C peaks appear around 160-185 ppm.<br />Nitrile 13C peaks appear around 115-130 ppm.<br />The 1H peak for a carboxylic acid proton appears around 12 ppm.<br />Practice with CONCEPTUAL CHECKPOINT 21.38.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-100<br />
  101. 101. 21.15 Spectroscopy of Carboxylic Acids and Their Derivatives<br />Predict the number and chemical shift of all 13C peaks for the molecule below.<br />Predict the number, chemical shift, multiplicity, and integration of all 1H peaks for the molecule below.<br />Copyright 2012 John Wiley & Sons, Inc.<br />Klein, Organic Chemistry 1e<br />21-101<br />

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