Free energy relationship of substituent effects on nucleophilic substitution reactions of butyl methyl chlorophosphate with pyridines in acetonitrile

초록

The general optimised method for the synthesis of butyl methyl chlorophosphate (3) is described under mild conditions. The target compounds were characterised by 1H-NMR, 13C-NMR, 31P-NMR and MS spectra. The nucleophilic substitution reactions of butyl methyl chlorophosphate (3) with X-pyridines were kinetically investigated in MeCN at 35.0 degrees C. The free energy relationship with X in the pyridines exhibits a biphasic concave upwards with a break point at X = 3-MeO. The selectivity parameters rho X (=-5.47 and -3.92) are large negatives, whereas beta X (=1.13 and 0.59) are small positives. The substituent effect on the reactions is great and significant. The energy of activation was calculated computationally using the Gaussian (ver. 16) software suite and DFT methodology and employed to study nucleophilic interactions from both the front- and backsides. These interactions are consistent with experimental observations and are well-supported by the DFT-calculated energy profiles. A concerted mechanism is proposed based on the observed results and especially the relatively small beta X value. The frontside and backside nucleophilic attacks are proposed with a change of substituted effects from strongly to weakly basic pyridines respectively.

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