Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue

We report the synthesis of N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide, , its N-pivaloyloxy analogue, , and improved synthesis of indole-2-acetonitrile, (70% in five steps from indole-2-carboxylic acid), the carcinogenic amine Trp-P-2, (40% from ), and the nitro compound, (40% from by oxidation with H2O2 using Mo(CO)6 catalyst). In aqueous solution at neutral pH, primarily undergoes C–O bond cleavage to yield the hydroxamic acid, , but under the same conditions the sterically hindered decomposes predominately by N–O bond cleavage with a pH independent rate constant that is 7.5-fold smaller than that for . In the pH range 0.5–7.0 three different processes for the decomposition of were detected by kinetics. Only the process that dominates at neutral pH generates a nitrenium species that can be trapped by N3−.