Nucleophilic reactions of carbonyl groups

1. Nucleophilic reactions of carbonyl groups • Oxygen is more electronegative than carbon (3.5 vs 2.5) and, therefore, a C=O group is polar

2. Under basic conditions -> Nucleophilic addition Under acidic conditions -> Electrophilic addition

3. Nucleophilic reactions of Ketones and Aldehydes • the functional group of an aldehyde is a carbonyl group bonded to a H atom • the functional group of a ketone is a carbonyl group bonded to two carbon atoms • aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipole interactions • they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

4. Nomenclature • IUPAC names: • the parent chain is the longest chain that contains the carbonyl group • for an aldehyde, change the suffix from -e to -al • for a cyclic molecule in which -CHO is bonded to the ring, add the suffix –carbaldehyde • For a ketone, change the suffix from –e to –one • for an unsaturated aldehyde or ketone, show the carbon-carbon double bond by changing the infix from -an- to -en-; the location of the suffix determines the numbering pattern

5. Nomenclature

6. Nomenclature • Common names • for an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid • for a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone

7. Nucleophilic reactions of Ketones and Aldehydes

8. Nucleophilic reactions of Ketones and Aldehydes – Nucleophile as leaving group For base-catalysed reaction: For acid-catalysed reaction:

9. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Addition of 1 mol of Alcohol to Aldehyde -> Hemiacetal Addition of 1 mol of Alcohol to Keton -> Hemiketal

10. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile

11. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Sugars form stable hemiacetals or hemiketals in solution Glucose can form 5- and 6-ring hemiacetals. Anomeric center/carbon Mixture of α and β is NOT racemat -> Mixture of diastereoisomers (since there are other chiral centers in the molecule)

12. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Mutarotation -> in solution

13. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Ribose can form 5- and 6-ring hemiacetals

14. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Ribose can form 5- and 6-ring hemiacetals

15. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Biological important hemiacetals -> sugars Ribonucleic Acids -> RNA Deoxyribonucleic Acids -> DNA

16. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Biological important hemiacetals -> sugars Coenzyme A -> transfers acetyl ATP -> high energy transfer compound

17. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Addition of 2 mol of Alcohol to Aldehyde -> Acetal Addition of 2 mol of Alcohol to Keton -> Ketal

18. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Acetal and ketal linkages are found in sugars and polysaccharides -> Formation of sucrose

19. Nucleophilic reactions of Ketones and Aldehydes – Oxygen as a nucleophile Acetal and ketal linkages are found in sugars and polysaccharides -> Formation of Polysaccharides Starch: Amylase + Amylopectine Cellulose: acetal linkage β1->4

20. Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophileReduction of aldehydes and ketons Complex metal hydrides (LiAlH4 or NaBH4) can deliver hydride -> they act like nucleophiles

21. Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophileReduction of aldehydes and ketons

22. Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophileReduction of aldehydes and ketons

23. Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophileReduction of aldehydes and ketons

24. Nucleophilic reactions of Ketones and Aldehydes – Carbon as a nucleophile Cyanide -> Cyanohydrin

25. Nucleophilic reactions of Ketones and Aldehydes – Carbon as a nucleophile Cyanide -> also toxic compounds in plants (laurel, bitter almonds)

26. Nucleophilic reactions of Ketones and Aldehydes – Carbon as a nucleophile Organometallics: Grignard reagents

27. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Addition of primary amine to carbonyl -> Imine (Schiff base)

28. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Addition of primary amine to carbonyl -> Imine (Schiff base) Equilibrium Stronger acid -> deprotonates -> Imine

29. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Imine (Schiff base) are nitrogen analogues of carbonyl groups =>

30. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Imine (Schiff base) are nitrogen analogues of carbonyl groups

31. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Imine (Schiff base) are nitrogen analogues of carbonyl groups -> Nitriles are also carbonyl-like compounds

32. Nucleophilic reactions of Ketones and Aldehydes – Nitrogen as a nucleophile Imine (Schiff base) are nitrogen analogues of carbonyl groups -> Nitriles are also carbonyl-like compounds