peri-Dimethylamino substituent effects on proton transfer at carbon in α-naphthylacetate esters: a model for mandelate racemase

Delley, R.J.; Bandyopadhyay, S.; Fox, M.A.; Schliehe, C.; Hodgson, D.R.W.; Hollfelder, F.; Kirby, A.J.; O'Donoghue, A.C.

Abstract

The rate constants for exchange of hydrogen for deuterium at the α-CH2 positions of 8-(N,N-dimethylaminonaphthalen-1-yl)acetic acid tert-butyl ester 1 and naphthalen-1-ylacetic acid tert-butyl ester 2 have been determined in potassium deuteroxide solutions in 1 : 1 D2O : CD3CN, in order to quantify the effect of the neighbouring peri-dimethylamino substituent on α-deprotonation. Intramolecular general base catalysis by the (weakly basic) neighbouring group was not detected. Second-order rate constants, kDO, for the deuterium exchange reactions of esters 1 and 2 have been determined as 1.35 × 10−4 M−1 s−1 and 3.95 × 10−3 M−1 s−1, respectively. The unexpected 29-fold decrease in the kDO value upon the introduction of a peri-dimethylamino group is attributed to an unfavourable steric and/or electronic substituent effect on intermolecular deprotonation by deuteroxide ion. From the experimental kDO values, carbon acid pKa values of 26.8 and 23.1 have been calculated for esters 1 and 2.

Citation

Delley, R., Bandyopadhyay, S., Fox, M., Schliehe, C., Hodgson, D., Hollfelder, F., …O'Donoghue, A. (2012). peri-Dimethylamino substituent effects on proton transfer at carbon in α-naphthylacetate esters: a model for mandelate racemase. Organic and Biomolecular Chemistry, 10(3), 590-596. https://doi.org/10.1039/c1ob06525d

• Journal Article Type: Article
• Acceptance Date: Oct 11, 2011
• Publication Date: Jan 21, 2012
• Deposit Date: Feb 17, 2012
• Publicly Available Date: Feb 15, 2016
• Journal: Organic and Biomolecular Chemistry
• Print ISSN: 1477-0520
• Electronic ISSN: 1477-0539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 3
• Pages: 590-596
• DOI: https://doi.org/10.1039/c1ob06525d
• Public URL: https://durham-repository.worktribe.com/output/1481423