1 / 45

Chapter 21 Ester Enolates

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

taipa
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 pKa’s

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

  4. O O C C R C OR' H H Introduction • The preparation and reactions of b-dicarbonyl compounds, especially b-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(gives -keto esters)

  9. O O O 2RCH2COR' RCH2CCHCOR' R The Claisen Condensation 1. NaOR' • b-Keto esters are made by the reaction shown, which is called the Claisen condensation. • Ethyl esters are typically used, with sodium ethoxide as the base. + R'OH 2. H3O+

  10. O O O 2CH3COCH2CH3 CH3CCH2COCH2CH3 Example 1. NaOCH2CH3 • Product from ethyl acetate is called ethylacetoacetateor acetoaceticester. 2. H3O+ (75%)

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

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

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

  14. •• O O •• – CH2 COCH2CH3 •• Mechanism Step 2: •• •• CH3COCH2CH3

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

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

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

  18. •• •• 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. +

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

  20. •• 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 ••

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

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

  23. 21.3Intramolecular Claisen Condensation:The Dieckmann Reaction

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

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

  26. •• •• O O •• •• – CH3CH2OCCH2CH2CH2CHCOCH2CH3 •• via

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

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

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

  30. 21.4Mixed Claisen Condensations

  31. 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.

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

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

  34. 21.5Acylation of Ketones with Esters

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

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

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

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

  39. 21.6Ketone Synthesis via b-Keto Esters

  40. O O O RCH2CCHCOH R Ketone Synthesis • b-Keto acids decarboxylate readily to give ketones (Section 19.17). + RCH2CCH2R CO2

  41. O O O O RCH2CCHCOR' RCH2CCHCOH R R Ketone Synthesis H2O • b-Keto acids decarboxylate readily to give ketones (Section 19.17). • b-Keto acids are available by hydrolysis of b-keto esters. + R'OH

  42. O O O 2RCH2COR' RCH2CCHCOR' R Ketone Synthesis 1. NaOR' • b-Keto acids decarboxylate readily to give ketones (Section 19.17). • b-Keto acids are available by hydrolysis of b-keto esters. • b-Keto esters can be prepared by the Claisen condensation. + R'OH 2. H3O+

  43. O 2 CH3CH2CH2CH2COCH2CH3 O O CH3CH2CH2CH2CCHCOCH2CH3 CH2CH2CH3 Example 1. NaOCH2CH3 2. H3O+ (80%)

  44. O O CH3CH2CH2CH2CCHCOH CH2CH2CH3 O O CH3CH2CH2CH2CCHCOCH2CH3 CH2CH2CH3 Example 1. KOH, H2O, 70-80°C 2. H3O+

  45. O O CH3CH2CH2CH2CCHCOH CH2CH2CH3 Example 70-80°C O CH3CH2CH2CH2CCH2CH2CH2CH3 (81%)

More Related