1 / 54

Chapter 21 Ester Enolates

Chapter 21 Ester Enolates. 21.1 Ester a -Hydrogens and their pK a s. Introduction. O. O. O. Protons a to an ester carbonyl group are less acidic, pK a  24, than a protons of aldehydes and ketones, pK a  16-20 .

alban
Download Presentation

Chapter 21 Ester Enolates

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. Chapter 21Ester Enolates

  2. 21.1Ester a-Hydrogens and their pKas

  3. Introduction O O O • Protons a to an ester carbonyl group are less acidic, pKa 24, than a protons of aldehydes and ketones, pKa 16-20. • The decreased acidity is due to the decreased electron-withdrawing ability of an ester carbonyl. • Electron delocalization decreases the positive character of the ester carbonyl group. O R O R O R H H H

  4. O O C C R C OR' H H Introduction • The preparation and reactions of -dicarbonyl compounds, especially -keto esters, is the main focus of this chapter. • A proton on the carbon flanked by the two carbonyl groups is relatively acidic, easily and quantitatively removed by alkoxide ions.

  5. O O C C R C OR' H H – CH3CH2O O O C C •• R C OR' – H Introduction pKa ~ 11

  6. •• •• •• •• – O O O O •• •• •• •• •• C C C C •• R C OR' R C OR' – H H Introduction • The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups.

  7. •• •• O O O O •• •• •• •• •• C C C C •• R C OR' R C OR' – H H Introduction •• •• • The resulting carbanion is stabilized by enolate resonance involving both carbonyl groups.

  8. 21.2The Claisen Condensation

  9. O O O RCH2CCHCOR' R The Claisen Condensation 1. NaOR' • -Keto esters are prepared by a reaction known as the Claisen condensation. • Ethyl esters are typically used, with sodium ethoxide as the base. + 2 RCH2COR' R'OH 2. H3O+

  10. O O CH3CCH2COCH2CH3 Example O 1. NaOCH2CH3 • Product from ethyl acetate is called ethyl acetoacetate or acetoacetic ester. 2 CH3COCH2CH3 2. H3O+ (75%)

  11. •• O •• – •• CH3CH2 CH2 O H COCH2CH3 •• •• •• O •• – •• CH3CH2 CH2 O H COCH2CH3 •• •• Mechanism Step 1:

  12. •• O •• •• CH2 COCH2CH3 •• O •• – CH2 COCH2CH3 •• Mechanism Step 1: • Anion produced is stabilized by electron delocalization; it is the enolate of an ester.

  13. •• – •• O O •• •• •• CH3C CH2 COCH2CH3 OCH2CH3 •• •• •• O O •• – CH2 COCH2CH3 •• Mechanism Step 2: •• •• CH3COCH2CH3

  14. •• – •• O O •• •• •• CH3C CH2 COCH2CH3 OCH2CH3 •• •• •• •• O O •• •• – •• + CH3C CH2 OCH2CH3 COCH2CH3 •• •• Mechanism Step 3:

  15. •• •• O O •• •• – •• CH3C CH2 OCH2CH3 COCH2CH3 •• •• Mechanism Step 3: • The product at this point is ethyl acetoacetate. • However, were nothing else to happen, the yield of ethyl acetoacetate would be small because the equilibrium constant for its formation is small. • Something else does happen. Ethoxide abstracts a proton from the CH2 group to give a stabilized anion. The equilibrium constant for this reaction is favorable. +

  16. •• •• O O •• •• •• – + OCH2CH3 CH3C CH H COCH2CH3 •• •• •• •• O O •• •• – •• CH3C CH2 OCH2CH3 COCH2CH3 •• •• Mechanism Step 4: +

  17. •• O O •• CH3C CH Mechanism Step 5: •• • In a separate operation, the reaction mixture is acidified. This converts the anion to the isolated product, ethyl acetoacetate. – COCH2CH3 ••

  18. •• H O O •• + O CH3C CH H •• H •• •• O H O •• •• CH3C CH O COCH2CH3 •• •• H H Mechanism Step 5: •• – COCH2CH3 •• +

  19. O 2CH3CH2COCH2CH3 1. NaOCH2CH3 2. H3O+ O O CH3CH2CCHCOCH2CH3 CH3 Another example • Reaction involves bond formation between the  carbon of one ethyl propanoate molecule and the carbonyl carbon of the other. (81%)

  20. 21.3Intramolecular Claisen Condensation:The Dieckmann Reaction

  21. O O 1. NaOCH2CH3 2. H3O+ O O COCH2CH3 (74-81%) Example CH3CH2OCCH2CH2CH2CH2COCH2CH3

  22. •• O O •• •• •• O O •• •• – CH3CH2OCCH2CH2CH2CHCOCH2CH3 •• via CH3CH2OCCH2CH2CH2CH2COCH2CH3 NaOCH2CH3

  23. •• •• – O CH3CH2O •• •• •• •• O •• C CHCOCH2CH3 H2C H2C CH2 •• •• O O •• •• – CH3CH2OCCH2CH2CH2CHCOCH2CH3 •• via

  24. •• •• – O CH3CH2O •• •• •• •• O •• C CHCOCH2CH3 H2C H2C CH2 via

  25. •• •• – O CH3CH2O •• •• •• •• O •• C CHCOCH2CH3 H2C H2C CH2 •• O •• •• O •• C •• – + CH3CH2O CHCOCH2CH3 H2C •• •• H2C CH2 via

  26. 21.4Mixed Claisen Condensations

  27. Mixed Claisen Condensations • As with mixed aldol condensations, mixedClaisen condensations are best carried outwhen the reaction mixture contains one compound that can form an enolate and another that cannot.

  28. O O O O HCOR ROCOR ROC COR O COR Mixed Claisen Condensations • These types of esters cannot form an enolate.

  29. O O COCH3 CH3CH2COCH3 O O (60%) CCHCOCH3 CH3 Example + 1. NaOCH3 2. H3O+

  30. 21.5Acylation of Ketones with Esters

  31. Acylation of Ketones with Esters • Esters that cannot form an enolate can be used to acylate ketone enolates.

  32. O O CH3CH2OCOCH2CH3 1. NaH 2. H3O+ O O COCH2CH3 (60%) Example +

  33. O O COCH2CH3 CH3C 1. NaOCH2CH3 2. H3O+ O O CCH2C (62-71%) Example +

  34. O O CH3CH2CCH2CH2COCH2CH3 1. NaOCH3 2. H3O+ O O CH3 (70-71%) Example

  35. 21.6Ketone Synthesis via -Keto Esters

  36. O O O RCH2CCHCOH R Ketone Synthesis • -Keto acids decarboxylate readily to give ketones. • (You don’t need to know the mechanism, although it is summarized in Section 19.17, if you are curious.) + RCH2CCH2R CO2

  37. O O O O RCH2CCHCOR' RCH2CCHCOH R R Ketone Synthesis H2O • -Keto acids decarboxylate readily to give ketones. • -Keto acids are available by hydrolysis of -keto esters. + R'OH

  38. O O O RCH2CCHCOR' R Ketone Synthesis 1. NaOR' • -Keto acids decarboxylate readily to give ketones. • -Keto acids are available by hydrolysis of -keto esters. • -Keto esters can be prepared by the Claisen condensation. + 2 RCH2COR' R'OH 2. H3O+

  39. O 2 CH3CH2CH2CH2COCH2CH3 O O CH3CH2CH2CH2CCHCOCH2CH3 CH2CH2CH3 Example 1. NaOCH2CH3 Claisen condensation of ester to form -keto ester. 2. H3O+ (80%)

  40. O O CH3CH2CH2CH2CCHCOH CH2CH2CH3 O O CH3CH2CH2CH2CCHCOCH2CH3 CH2CH2CH3 Example 1. KOH, H2O, 70-80°C Hydrolysis of -keto ester to form -keto acid. 2. H3O+

  41. O O CH3CH2CH2CH2CCHCOH CH2CH2CH3 O CH3CH2CH2CH2CCH2CH2CH2CH3 Example Decarboxylation of -keto acid to form ketone. 70-80°C (81%)

  42. 21.7The Acetoacetic Ester Synthesis

  43. O O C C H3C C OCH2CH3 H H Acetoacetic Ester • Acetoacetic ester is another name for ethyl acetoacetate. • The "acetoacetic ester synthesis" uses acetoacetic ester as a reactant for the preparation of ketones.

  44. O O C C H3C C OCH2CH3 H H O O C C •• CH3CH2OH + H3C C OCH2CH3 – pKa ~ 16 H Deprotonation of Ethyl Acetoacetate – + CH3CH2O • Ethyl acetoacetate can be converted readily to its anion with bases such as sodium ethoxide. pKa ~ 11

  45. O O C C •• H3C C OCH2CH3 – H R X O O C C H3C C OCH2CH3 H R Alkylation of Ethyl Acetoacetate • The anion of ethyl acetoacetate can be alkylated using an alkyl halide (SN2: methyl and primary alkyl halides work best; secondary alkyl halides work also but give lower yields; tertiary alkyl halides undergo elimination).

  46. O O C C H3C C OH H R 1. HO–, H2O 2. H+ O O C C H3C C OCH2CH3 H R Conversion to Ketone • Saponification and acidification convert the alkylated derivative to the corresponding -keto acid. • The -keto acid then undergoes decarboxylation to form a ketone.

  47. O O C C H3C C OH H R O Conversion to Ketone • Saponification and acidification convert the alkylated derivative to the corresponding -keto acid. • The -keto acid then undergoes decarboxylation to form a ketone. heat + C CO2 H3C CH2R

  48. O O CH3CCH2COCH2CH3 O O CH3CCHCOCH2CH3 CH2CH2CH2CH3 (70%) Example 1. NaOCH2CH3 2. CH3CH2CH2CH2Br

  49. O (60%) CH3CCH2CH2CH2CH2CH3 1. NaOH, H2O 2. H+ 3. heat, -CO2 O O CH3CCHCOCH2CH3 CH2CH2CH2CH3 Example

  50. O O CH3CCHCOCH2CH3 CH2 CH2CH 1. NaOCH2CH3 2. CH3CH2I O O CH3CCCOCH2CH3 CH2 CH2CH CH3CH2 (75%) Example: Dialkylation

More Related