A carbon-13 NMR study of new 4-substituted neostigmine methyl sulphates: Correlations of substituent induced chemical shifts with substituent parameters

The Carbon-13 NMR spectra of six new neostigimine derivatives, the 4-substi tuted-3-[{N,N-dimethylamino)carbonyl}oxy]-N',N',N'-trimethylbenzen-anminium methyl sulphates (4-substituted neostigmine methyl sulphates), and of the parent compound were recorded, and unequivocal chemical shift assignments t hrough the use of HETCOR and COLOC sequences were performed. Large intramol ecular interaction chemical shifts (ICS) were observed for carbon C-3 (-8.3 to +3.1 ppm), attachment site of the OC(O)N(CH3)(2) group, and moderate IC S values (-3.3 to +3.5 ppm) for the remaining ring carbons, similarly to th e values which were found for C-1 (-9.3 to +3.4 ppm) and for C-2 to C-6 (-3 .0 to +3.8 ppm) of the corresponding 2 -substituted-5-N', N'-dimethylaminop henyl-N, N-dimethylcarbamates. Correlation analyses for the substituent-ind uced chemical shifts (SCS) with several sets of substituent parameters were carried out, through SSP, DSP and DSP-NLR treatments, as well as through m ultiple regression analysis. Good correlations were found for all ring carb ons (r>0.97) and for the carbonyl carbon (r 0.9797). Resonance contribution is predominant for C-l and C-2, while the electronegativity or inductive p arameter is significant or the prevailing component for all ring carbons. N egative r values were found for several correlations (reverse substituent e ffect).