Acyl Insertions (J&F Ch. 18) Chemistry 125: Lecture 72 April 22, 2011 Acyl Insertions (J&F Ch. 18) -H Reactivity (J&F Ch. 19) Condensations (J&F Ch. 19) This For copyright notice see final page of this file

C O Y X R Acyl Insertions O R NH R CH2 OH Baeyer-Villiger Beckmann ketone ester NH R Beckmann ketone amide CH2 OH Arndt-Eistert lengthen chain

Baeyer-Villiger Reaction - 1900 (insert O) (e.g. J&F pp. 907-909)

Beckmann Rearrangement – 1886 (insert N) (e.g. J&F pp. 909-911)

Arndt-Eistert Homologation – 1935 (insert C) (e.g. J&F pp. 915-917)

 Acidity (J&F Tables 19.1 (p. 933), 19.2 (p. 943), 19.3 (p. 958)) pKa pKa 17 9 19 11 24 weaker than H-OH stronger than H-OH except 13 24 18 18 25 11

LDA hindered strong base (pKa = 36) (J&F p. 944) Lithium Diisopropyl Amide K ~ 1011 pKa ~ 25 complete formation even of amide enolate not just a little at equilibrium (slow attack on C=O, none on enolate)

Nucleophilic a-Carbon

Acid & Base  H/D Exchange via enol and enolate (e.g. J&F Sec. 19.2a) -OD D-OD

Racemization via enol and enolate (e.g. J&F Sec. 19.3) H enol enolate A B H both planar

-Halogenation Ketones / Aldehydes (e.g. J&F Sec. 19.4a) I-I I enol enolate

-Halogenation Ketones / Aldehydes (e.g. J&F Sec. 19.4a) Diiodomethyl Iodomethyl pKa ~14 R-COO- + HCI3 Andel Früh Iodoform is a bright yellow solid + I R-COOH + -CI3 I I I-I I Thus the Iodoform Test for methyl ketones enol + I I enolate HO- I -OH I I

-Halogenation Carboxylic Acids Cl O Cl- O Cl O- S O Cl O- SO2 Cl Cl- O S O Cl X = Cl ; Y = Cl + stable SO2 Hell-Volhard-Zelinsky ~1885 (e.g. J&F Sec.19.4b) PBr3

-Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a)

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