Chapter 19 Substitutions at the Carbonyls Organic Chemistry II Fall 1999 Chapter 19 Substitutions at the Carbonyls  804 Fig. 19.1 reactivity of carbonyls:  807 Table 19.1 resonance, inductive & steric effects:  806 bottom stability of Y-: equilibrium,  807 mid. (Prob. 19.2) practice:  805-808, Problem 19.1-19.4 OrgChem-Chap19 Chapter 15

Carboxylic Acid Derivatives: RCO-Y (I) Organic Chemistry II Fall 1999 Carboxylic Acid Derivatives: RCO-Y (I) acyl (acid) chlorides: RCO-Cl (chloride) SOCl2, PCl3, PCl5;  809 Figure 19.2 ( 360) the most reactive: preparation of other derivatives anhydrides: RCO-OCOR’ (carboxylic acid) from acyl chlorides: with a base,  810 bottom dehydration of acids: equilibrium,  811 top practice:  810-811, Problem 19.5-19.6 OrgChem-Chap19 Chapter 15

Carboxylic Acid Derivatives: RCO-Y (II) Organic Chemistry II Fall 1999 Carboxylic Acid Derivatives: RCO-Y (II) esters: RCO-OR’ (alcohol) from acyl chlorides / anhydrides:  811 bot.-812 top Fischer esterification: acid & alcohol,  812 middle mechanism: acid catalyst/equilibrium,  813 Figure 19.3 lactones: cyclic esters,  813 top practice:  814, Problem 19.7-19.9 OrgChem-Chap19 Chapter 15

Carboxylic Acid Derivatives: RCOY (III) Organic Chemistry II Fall 1999 Carboxylic Acid Derivatives: RCOY (III) amides: RCO-NR’R’’ (amine) from acyl chlorides / anhydrides:  824 top 1 eq. of base required not to protonate the amine from acids: lactams / imides,  824 bottom 5- or 6-membered rings favored type of amides: 1o: -NH2, 2o: -NHR, 3o: -NR1R2 practice:  825, Problem 19.15 OrgChem-Chap19 Chapter 15

Preparation of Carboxylic Acids Organic Chemistry II Fall 1999 Preparation of Carboxylic Acids hydrolysis of acid derivatives: RCOY  RCO2H acyl chlorides & anhydrides: reactive,  815 middle esters: acidic / basic conditions,  816 Figure 19.4 preparation of soap: saponification,  819-20, Focus On cleavage of the acyl C-O bond: isotopic exp.;  817 top amides: harsh conditions, Figure 19.5 &  819 top nitriles: amide intermediate,  822 & Figure 19.6 R-CO2H  R-CH2X  R-CH2CO2H:  823 top practice:  815-823, Problem 19.10-13 OrgChem-Chap19 Chapter 15

Hydride Addition: LiAlH4, Alcohols Organic Chemistry II Fall 1999 Hydride Addition: LiAlH4, Alcohols RCOCl/RCO2COR’/RCO2R’/(RCO2H): RCH2OH 1o alcohols: 2(3) eq. of H-, Figure 19.7-8 &  827 bot. NaBH4: slow with esters,  828 middle reaction RCONR’R”/RCN: amines,  829 & Figure 19.9 RCOCl  RC(O)H: LiAlH(OtBu)3 (LTBA),  831 RCO2R’  RC(O)H: (i-Bu)2AlH (DIBALH),  832 practice:  827-832, Problem 19.17-19.20 OrgChem-Chap19 Chapter 15

Organometallic Addition Organic Chemistry II Fall 1999 Organometallic Addition organolithium/Grignard reagents: alcohols RCOCl/RCO2COR’/RCO2R’:  833 & Fig 19.10 addition to RCN: ketone,  834 bot & Fig 15.11 organocuprates: slow with RCHO/RCOR’ RCOCl:  834 middle reactions practice:  834-35, Problem 19.22-19.24 OrgChem-Chap19 Chapter 15

Sulfur & Phosphorus Analogues Organic Chemistry II Fall 1999 Sulfur & Phosphorus Analogues sulfonic acid: RSO2-OH RSO2-Cl (sulfonyl chloride), RSO2-OR’ (sulfonate), RSO2-NR’R” (sulfonamide):  836-837 phosphoric acid: (O)P(OH)3;  837-838 (O)P-Cl3 (phosphoryl chloride), (HO)2P(O)-O-(O)P(HO)2 (pyrophosphoric acid), (O)P-(OR)3’ (triphosphate), (O)P-(NR2)3’ (phosphoric triamide) nerve gases & pesticides:  838-9 Focus On review:  841-2, Table 19.2 OrgChem-Chap19 Chapter 15