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 –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 Nucleophilic reactions of Ketones and Aldehydes

4 Nomenclature IUPAC names: –the parent chain is the longest chain that contains the carbonyl group -e-al –for an aldehyde, change the suffix from -e to -al carbaldehyde –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 -an--en- –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 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 Anomeric center/carbon Mixture of α and β is NOT racemat -> Mixture of diastereoisomers (since there are other chiral centers in the molecule) Glucose can form 5- and 6-ring hemiacetals.

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 nucleophile Reduction of aldehydes and ketons Complex metal hydrides (LiAlH 4 or NaBH 4 ) can deliver hydride -> they act like nucleophiles

21 Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophile Reduction of aldehydes and ketons

22 Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophile Reduction of aldehydes and ketons

23 Nucleophilic reactions of Ketones and Aldehydes – Hydride as a nucleophile Reduction 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