title: peri-Dimethylamino substituent effects on proton transfer at carbon in α-naphthylacetate esters: a model for mandelate racemase.
abstract: The rate constants for exchange of hydrogen for deuterium at the α-CH(2) 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 D(2)O : CD(3)CN, 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, k(DO), 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 k(DO) 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 k(DO) values, carbon acid pK(a) values of 26.8 and 23.1 have been calculated for esters 1 and 2.
authors: Department of Chemistry, University of Durham, South Road, Durham, UK DH1 3LE.
authors: Richard J
authors: RJ
authors: Delley
authors: Subhajit
authors: S
authors: Bandyopadhyay
authors: Mark A
authors: MA
authors: Fox
authors: Constanze
authors: C
authors: Schliehe
authors: David R W
authors: DR
authors: Hodgson
authors: Florian
authors: F
authors: Hollfelder
authors: Anthony J
authors: AJ
authors: Kirby
authors: AnnMarie C
authors: AC
authors: O'Donoghue
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry*; D041961:Deuterium Exchange Measurement; D004123:Dimethylamines / Q000737:chemistry*; D004952:Esters; D006868:Hydrolysis; D007536:Isomerism; D009284:Naphthols / Q000737:chemistry*; D011522:Protons; D019998:Racemases and Epimerases / Q000378:metabolism*
chemical_list: D004123:Dimethylamines; D004952:Esters; D009284:Naphthols; D011522:Protons; C005366:naphthyl acetate; C034516:dimethylamine; D019998:Racemases and Epimerases; C021540:mandelate racemase