1 / 21

21.8 Barbiturates

21.8 Barbiturates. O. COCH 2 CH 3. H 2 N. H 2 C. C. O. COCH 2 CH 3. H 2 N. O. Barbituric acid is made from diethyl malonate and urea. +. O. COCH 2 CH 3. H 2 N. H 2 C. C. O. COCH 2 CH 3. H 2 N. O. O. H. N. C. C. O. H 2 C. N. C. O. H.

helki
Download Presentation

21.8 Barbiturates

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. 21.8Barbiturates

  2. O COCH2CH3 H2N H2C C O COCH2CH3 H2N O Barbituric acid is made from diethyl malonate and urea +

  3. O COCH2CH3 H2N H2C C O COCH2CH3 H2N O O H N C C O H2C N C O H Barbituric acid is made from diethyl malonate and urea + 1. NaOCH2CH3 2. H+ (72-78%)

  4. O COCH2CH3 H2N H2C C O COCH2CH3 H2N O Barbituric acid is made from diethyl malonate and urea + H O 1. NaOCH2CH3 N 2. H+ O N O (72-78%) H

  5. O O COCH2CH3 COCH2CH3 R H2C C R' COCH2CH3 COCH2CH3 O O Substituted derivatives of barbituric acid are madefrom alkylated derivatives of diethyl malonate 1. RX, NaOCH2CH3 2. R'X, NaOCH2CH3

  6. O O H COCH2CH3 N O (H2N)2C R R C O R' R' N COCH2CH3 H O O Substituted derivatives of barbituric acid are madefrom alkylated derivatives of diethyl malonate

  7. O H N CH3CH2 O CH3CH2 N H O 5,5-Diethylbarbituric acid(barbital; Veronal) Examples

  8. H3C CH3CH2CH2CH Examples O H N O CH3CH2 N H O 5-Ethyl-5-(1-methylbutyl)barbituric acid(pentobarbital; Nembutal)

  9. H3C CH3CH2CH2CH CHCH2 H2C Examples O H N O N H O 5-Allyl-5-(1-methylbutyl)barbituric acid(secobarbital; Seconal)

  10. 21.9Michael Additions of Stabilized Anions

  11. O O C C •• H3C C OCH2CH3 – H O O C C •• C OCH2CH3 CH3CH2O – H Stabilized Anions • The anions derived by deprotonation of b-keto esters and diethyl malonate are weak bases. • Weak bases react with a,b-unsaturated carbonyl compounds by conjugate addition.

  12. O O O H2C CHCCH3 CH3CH2OCCH2COCH2CH3 Example +

  13. O O O H2C CHCCH3 CH3CH2OCCH2COCH2CH3 O O CH3CH2OCCHCOCH2CH3 CH2CH2CCH3 O Example + KOH, ethanol (85%)

  14. O CH3CCH2CH2CH2COH O O CH3CH2OCCHCOCH2CH3 CH2CH2CCH3 O O Example (42%) 1. KOH, ethanol-water 2. H+ 3. heat

  15. 21.10a-Deprotonation of Carbonyl Compoundsby Lithium Dialkylamides

  16. Deprotonation of Simple Esters • Ethyl acetoacetate (pKa ~11) and diethyl malonate (pKa ~13) are completely deprotonated by alkoxide bases. • Simple esters (such as ethyl acetate) are not completely deprotonated, the enolate reacts with the original ester, and Claisen condensation occurs. • Are there bases strong enough to completely deprotonate simple esters, giving ester enolates quantitatively?

  17. CH3 CH3 – + •• Li C N C H H •• CH3 CH3 Lithium diisopropylamide • Lithium dialkylamides are strong bases (just as NaNH2 is a very strong base). • Lithium diisopropylamide is a strong base, but because it is sterically hindered, does not add to carbonyl groups.

  18. O CH3CH2CH2COCH3 O + Li CH3CH2CHCOCH3 Lithium diisopropylamide (LDA) • Lithium diisopropylamide converts simple esters to the corresponding enolate. + LiN[CH(CH3)2]2 pKa ~ 22 – + + HN[CH(CH3)2]2 •• pKa ~ 36

  19. O CH3CH2CHCOCH3 Lithium diisopropylamide (LDA) • Enolates generated from esters and LDA can be alkylated. O CH3CH2CHCOCH3 CH2CH3 CH3CH2I (92%) – ••

  20. O CH3COCH2CH3 2. (CH3)2C O O HO C CH2COCH2CH3 H3C CH3 Aldol addition of ester enolates • Ester enolates undergo aldol addition to aldehydes and ketones. 1. LiNR2, THF 3. H3O+ (90%)

  21. O CH3CH2CC(CH3)3 O 2. CH3CH2CH O CH3CHCC(CH3)3 HOCHCH2CH3 Ketone Enolates • Lithium diisopropylamide converts ketones quantitatively to their enolates. 1. LDA, THF 3. H3O+ (81%)

More Related