An Improved Understanding of the Reaction of Bis(bromomethyl)quinoxaline 1-N-Oxides with Amines Using Substituent Effects

Abstract

The reaction of bis(bromomethyl)quinoxaline N-oxides with amines is interesting from a reaction mechanism perspective and due to the reported biological activity of compounds in this general class. The complex mechanism of this reaction (particularly in the case of primary amines) is complicated further when C6 or C7 substituted mono-N-oxides are considered. In this study, the synthesis and subsequent characterization of a series of 2,3-bis(bromomethyl)quinoxaline 1-N-oxides is reported. Experimental and computational evidence is used to show that the observed product ratios from the reaction with diethylamine reflect the influence of both the C6/C7 substituent and the N-oxide functional group on the initial nucleophilic substitution reaction.

Identification of conoidin A as a covalent inhibitor of peroxiredoxin II

“…Studies with model substrates have shown that 1 can react with both thiols and amines21 (see also below). To determine whether the biotinylated proteins in the parasite extract had reacted with 2 through a thiol(s) or an alternative protein nucleophile(s), duplicate parasite samples were extracted either in the presence or absence of iodoacetamide prior to incubation with 2 .…”

Optimisation of Conoidin A, a Peroxiredoxin Inhibitor

“…[8,9] Subsequent condensation of 4 with 1,2-phenylenediamine gave high yields of the mono-bromo quinoxaline 5 that was oxidised (mCPBA, 2 equiv) to give 2. The use of limited amounts of mCPBA led to a mixture of the two mono-Noxides 6 and 7, [10] as it was thought that pure samples of these two analogues would enable the role of the N-oxide functional groups to be explored.…”

Synthesis and dual D2and 5-HT1Areceptor binding affinities of 5-piperidinyl and 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones

“…The synthesis of the latter was envisioned by the Suzuki-Miyaura reaction of bromo-1H-benzo[d]imidazol-2(3H)-one (10) with boronate (12) [22]. Preparation of 10 was commenced by the basic hydrolysis of acetamide (7) to produce nitroaniline (8), which in turn was transformed to benzenediamine (9) by the action of stannous chloride 26 . Reaction of 9 with CDI finally produced 10 in 62% yield.…”