Question

nob 2. Strong acids always protonate amide oxygens and never protonate amide nitrogens. Provide two reasons that explain this fact (4 points).

Answer 1

2) Amide nitrogen line pair is in conjugation with carbonyl group and hence it is not available for the protonation. Whereas, the lone pair on oxygen is freely available for protonation and hence while reacting with strong acid the carbonyl oxygen is protonated first. Additionaly, the potonated carbonyl oxygen cation is stabilized by resonance. Br CN О. ОН CH2 Her H30+ CH, KCN "CHANCH EtOH ethenylbenzene (1-bromoethylbenzene 2-phenylpropanenitrile 2-phenylpropanoic acid CH3 1) CH3Mgi CH32 ) H3O+ KCN DMSO H3C Br 1-bromo-3-methylbutane CH3 I CH3 H3c CN H3C 4-methylpentanenitrile 5-methylhexan-2-one Н.С. Gilman reagent can be prepared from EtBr+ Li + Cul

H2C Et 1) EtMg Br(2 eq.). SOCI22 ) F EtOH I 2) H3O+ + HO. CH3 5 o CH3NH2 Cat. HCI Ph. * Ph, OEt ethylphenylacetate N-methyl-2-phenylacetamide NH CH₃