Acidities of glycine Schiff bases and alkylation of their conjugate bases

Martin J. O'Donnell, William D. Bennett, William A. Bruder, William N. Jacobsen, Keith Knuth, Brigitte LeClef, Robin L Polt, Frederick G. Bordwell, Susan R. Mrozack, Thomas A. Cripe

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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 pKa by 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa 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 pKa 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 pKHAs 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.

Original languageEnglish (US)
Pages (from-to)8520-8525
Number of pages6
JournalJournal of the American Chemical Society
Volume110
Issue number25
StatePublished - 1988
Externally publishedYes

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Schiff Bases
Alkylation
Acidity
Glycine
Amino acids
Negative ions
Anions
Substitution reactions
Derivatives
Hydrogen
Acids
ketimine

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

O'Donnell, M. J., Bennett, W. D., Bruder, W. A., Jacobsen, W. N., Knuth, K., LeClef, B., ... Cripe, T. A. (1988). Acidities of glycine Schiff bases and alkylation of their conjugate bases. Journal of the American Chemical Society, 110(25), 8520-8525.

Acidities of glycine Schiff bases and alkylation of their conjugate bases. / O'Donnell, Martin J.; Bennett, William D.; Bruder, William A.; Jacobsen, William N.; Knuth, Keith; LeClef, Brigitte; Polt, Robin L; Bordwell, Frederick G.; Mrozack, Susan R.; Cripe, Thomas A.

In: Journal of the American Chemical Society, Vol. 110, No. 25, 1988, p. 8520-8525.

Research output: Contribution to journalArticle

O'Donnell, MJ, Bennett, WD, Bruder, WA, Jacobsen, WN, Knuth, K, LeClef, B, Polt, RL, Bordwell, FG, Mrozack, SR & Cripe, TA 1988, 'Acidities of glycine Schiff bases and alkylation of their conjugate bases', Journal of the American Chemical Society, vol. 110, no. 25, pp. 8520-8525.
O'Donnell MJ, Bennett WD, Bruder WA, Jacobsen WN, Knuth K, LeClef B et al. Acidities of glycine Schiff bases and alkylation of their conjugate bases. Journal of the American Chemical Society. 1988;110(25):8520-8525.
O'Donnell, Martin J. ; Bennett, William D. ; Bruder, William A. ; Jacobsen, William N. ; Knuth, Keith ; LeClef, Brigitte ; Polt, Robin L ; Bordwell, Frederick G. ; Mrozack, Susan R. ; Cripe, Thomas A. / Acidities of glycine Schiff bases and alkylation of their conjugate bases. In: Journal of the American Chemical Society. 1988 ; Vol. 110, No. 25. pp. 8520-8525.
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T1 - Acidities of glycine Schiff bases and alkylation of their conjugate bases

AU - O'Donnell, Martin J.

AU - Bennett, William D.

AU - Bruder, William A.

AU - Jacobsen, William N.

AU - Knuth, Keith

AU - LeClef, Brigitte

AU - Polt, Robin L

AU - Bordwell, Frederick G.

AU - Mrozack, Susan R.

AU - Cripe, Thomas A.

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N2 - 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 pKa by 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa 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 pKa 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 pKHAs 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.

AB - 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 pKa by 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa 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 pKa 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 pKHAs 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.

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