SYNTHESIS AND CHARACTERIZATION OF ADDUCTS OF ALACHLOR AND 2-CHLORO-N-(2,6-DIETHYLPHENYL)ACETAMIDE WITH 2'-DEOXYGUANOSINE, THYMIDINE, AND THEIR 3'-MONOPHOSPHATES

Adducts of the preemergence herbicide o-N-(methoxymethyl)-N-(2,6-dieth ylphenyl)acetamide (alachlor) and 2-chloro-N-(2,6-diethylphenyl)acetam ide (CDEPA) with 2'-deoxyguanosine, thymidine, 2'-deoxyguanosine 3'-mo nophosphate, and thymidine 3'-monophosphate have been synthesized and characterized. Under mildly basic conditions alachlor and CDEPA form N -1 adducts with 2'-deoxyguanosine and N-3 adducts with thymidine as a result of chlorine displacement. In addition, alachlor formed an N-7 a dduct with 2'-deoxyguanosine, yl)-N-(2,6-diethylphenyl)carbamoyl]methy l]guanine. N-1 adducts of alachlor and CDEPA with 2'-deoxyguanosine 3' -monophosphate and N-3 adducts with thymidine 3'-monophosphate are als o described. In addition to spectroscopic data, structural proof inclu ded the dephosphorylation of each nucleotide adduct to its correspondi ng nucleoside adduct by nuclease P1. Alachlor and alachlor adducts but not CDEPA and CDEPA adducts exhibited rotational isomerism as evidenc ed by proton and C-13 NMR studies. These rotamers were attributed to h indered rotation about the shortened N-carbonyl bond. Computational me thods employing molecular mechanics and quantum mechanics were used to characterize the structures and energies of these rotamers to account for the patterns of duplicate NMR resonances observed.