Acidities of Glycine Schiff Bases and Alkylation of Their Conjugate Bases

Equilibrium acidities in Me₂SO are reported for six ketimines of the type Ph₂C=NCH(R)CO₂Et and five aldimines, ArCH=NCH(R)CO₂Et. Changing R in the ketimine from H to Ph increased the pK_a 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pK_a of 3.8 and 4.2 units observed for the replacement of hydrogen by Me and PhCH₂, respectively. Phase-transfer alkylation of the Ph₂C=NCH₂CO₂Et ketimine gave over 90% of monoalkylate whereas, under similar conditions, the aldimine 4-ClC₆H₄CH=NCH₂CO₂Et gave a mixture of mono- and dialkylate. The difference is that the pK_a of the monoalkylated aldimine is essentially the same as that of the parent, which leads to rapid equilibration with the parent anion and consequent dialkylation. The rates of alkylation in Me₂SO of these parent and monoalkylated anions did not differ greatly, showing that the relative pK_HAs of the parent acid and its monoalkyl derivative, rather than the relative rates of the mono- and dialkylation reactions, is the principal factor that determines the extent of the competition between monoalkylation and dialkylation.