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Chapter 20 Enolates / Other Carbon Nucleophiles

Chapter 20 Enolates / Other Carbon Nucleophiles. C-C bond formation is very important larger, more complex organic molecule can be made from smaller ones How? carbon nucleophile + carbon electrophile .

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Chapter 20 Enolates / Other Carbon Nucleophiles

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  1. Chapter 20 Enolates / Other Carbon Nucleophiles • C-C bond formation is very important • larger, more complex organic molecule can be made from smaller ones How? carbon nucleophile + carbon electrophile  Carbon electrophile: or + - +  abundant OrgChem-Chap20

  2. How about carbon nucloephile? limited Ex) cyanide ion: M+ -CN acetylide ion: ylide: Grignard reagent and organo metallic compound: R-X + 2Li  RLi + LiX OrgChem-Chap20

  3.  Grignard reagent and organometallic compund are not useful for SN2 reactions because they are too reactive. For the SN2 enolates are used Because they are not as reactive as organometallic compunds, then C-C bond through SN2 can be formed OrgChem-Chap20

  4. OrgChem-Chap20

  5. 20.1 Enols and Enolate Anions  both are possible under acidic and basic conditions In acidic condition In basic condition OrgChem-Chap20

  6. Equilibrium constants of carbonyl and enol tautomers for base condition Higher value for 1,3-dicarbonyl compounds diketone > ketoester > diester OrgChem-Chap20

  7. What kinds of base can we use? Use base whose pKas of conjugate acids are greater than those of the carbonyl base ! OrgChem-Chap20

  8. For Use compunds whose pKas of conjugate acids are greater than 30 such as For Ethoxide can be used (pKa ~ 16) OrgChem-Chap20

  9. 20.2 Halogenation of the -Carbon The reaction of an aldehyde or ketone with Cl2, Br2, or I2, under either acid or basic condition Both acidic and basis conditions can be used OrgChem-Chap20

  10. Under acidic conditions The presence of the halogens retards the enolation, so the addition of single halogen is possible Examples OrgChem-Chap20

  11. Under basic conditions OrgChem-Chap20

  12. Example OrgChem-Chap20

  13. 20.3 Alkylation of Enolate Anions • Enolates from esters, ketones, and nitriles can be used in SN2 reactions (alkylations). Ex) OrgChem-Chap20

  14. Aldehydes cannot be used in such reactions because they are too reactive (side reactions) 1. Reactions with base No steric hidrance ! 2. Reactions with themselves:Aldol condensation (later) LDA: lithium diisopropylamide  It is a very strong base but not very nucleophilic due to the steric hindrance OrgChem-Chap20

  15. To avoid the formation of two products, deprotonation of the ketones must produce a single enolate ion. Examples OrgChem-Chap20

  16. OrgChem-Chap20

  17. 20.4 Alkylation of More Stabilized Anions Strong nucleophiles are normally strong bases, then many side reactions are possible. Elimination Unwanted substitution OrgChem-Chap20

  18. Therefore we might need to use less nucleophilic enolates, Then we might need more steps to, still the yield can be higher due to less side reaction. Example Ch 10.2 Ch 10.6 OrgChem-Chap20

  19. Ch 10.2 OrgChem-Chap20

  20. Ch 10.6 Why? OrgChem-Chap20

  21. This time, ethyl acetoacetate can be used instead of acetone! OrgChem-Chap20

  22. Mechanism OrgChem-Chap20

  23. Example OrgChem-Chap20

  24. Diethyl malonatate can be used instead of acetic acid OrgChem-Chap20

  25. OrgChem-Chap20

  26. Preparation of substituted -ketoesters, -diester, and dinitrile  without hydrolysis OrgChem-Chap20

  27. OrgChem-Chap20

  28. 20.5 The Aldol Condensation (aldehyde + base) cannot be used for the alkylation of alkyl halide, because of the aldol condensation! Carbonyl carbon of aldehyde is much more electrophilic than those of ester, ketone, and nitrile! ester, ketone, and nitrile  SN2 OrgChem-Chap20

  29. <Mechanism> OrgChem-Chap20

  30. If the aldol condensation is conducted under very vigorous conditions (higher temperature, longer reaction time, and/or strong base OrgChem-Chap20

  31. <Examples> OrgChem-Chap20

  32. KetonesAs less electrophilic, usually no aldol condensation.However when the product is 5- or 6- membered ring, then aldol condensation occurs! <Example> OrgChem-Chap20

  33. Mixed aldol condensation 4 products = 2 acidic compounds x 2 electrophilic compounds OrgChem-Chap20

  34. Use aromatic aldehyde (only electrophilic) to get one product. Product is more favorable: conjugation <Example> OrgChem-Chap20

  35. <Examples> OrgChem-Chap20

  36. 20.6 Ester Condensation 20.3-4: enolates with alkyl halide using weak or strong bases depending on the acidity. OrgChem-Chap20

  37. 20.5: enolate with aldehyde using weaker bases.  Aldol condensation 20.6: enolate with ester using weaker bases. Ester condensation or Claisen ester condensation OrgChem-Chap20

  38. Mechanism of the Claisen Ester Condensation Step 4 is the reason why this reaction is possible OrgChem-Chap20

  39. For the compounds with only one on the -carbon, Step 4 is impossible. Then the ester condensation is impossible If stronger base is used, then condensation is possible OrgChem-Chap20

  40. Dieckmann condensatoin Intramolecular ester condensation Mixed ester condensation can be prevented if one of the component acts as only electrophile such as OrgChem-Chap20

  41. <Examples> OrgChem-Chap20

  42. 20.7 Carbon and hydrogen leaving groups A carbanion as a leaving group OrgChem-Chap20

  43. A hydride as a leaving group, Cannizzaro reaction OrgChem-Chap20

  44. 20.8 Enamines The enamine can be used as a carbon nucleophile ! In ch 18.8 OrgChem-Chap20

  45. -carbon is nucleophilic, still weaker nucleophile than the enolates. Therefore for SN2 reaction, the alkyl halide must be very reactive such as: <Examples> OrgChem-Chap20

  46. <Examples> OrgChem-Chap20

  47. 20.9 Other Carbon Nucleophiles OrgChem-Chap20

  48. Example reaction OrgChem-Chap20

  49. Example reaction OrgChem-Chap20

  50. Other Carbon Nucleophiles OrgChem-Chap20

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