Synthesis and Herbicidal Activity of Isoindoline-1,3-dione Substituted Benzoxazinone Derivatives Containing a Carboxylic Ester Group

Abstract

A carboxylic ester group was introduced to three series of isoindolinedione substituted benzoxazinone derivatives. Some of these analogues exhibited good herbicidal activities, and the injury symptoms against weeds included leaf cupping, crinkling, bronzing, and necrosis, typical of protox inhibitor herbicides. Structurally, they were classified as Chemical Group A (4-carboxylic ester group-6-isoindolinyl-benzoxazinones), B (4-carboxylic ester group-7-isoindolinyl-benzoxazinones), and C (4-carboxylic ester group-6- tetrahydroisoindolinyl-benzoxazinones). All of the tested compounds were structurally confirmed by (1)H NMR, IR, mass spectroscopy, and elemental analysis. Preliminary bioassay data of these three classes of compounds showed that, in general, the order of the herbicidal effectiveness is C > A > B. Several of the lead compounds, for example, C10 (methyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo[b][1,4] oxazin-4(3H)-yl) propano-ate), C12 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2- methyl-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) propanoate), and C13 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo-[b][1,4]oxazin-4(3H)-yl) butanoate), exhibited greater than 80% control at 75 g a.i./ha in both pre- and postemergence treatments against dicotyledonous weeds, such as Abutilon theophrasti Medic, Chenopodium album L., and Amaranthus ascendens L., and monocotyledon weeds, such as Digitaria sanguinalis L., Echinochloa crus-galli L., and Setaria viridis L. On the basis of advanced screening tests and crop selectivity, compounds C10, C12, and C13 are safer to crops than flumioxazin. Compounds C10, C12, and C13 are potent to develop as pre-emergent herbicides used in peanut, soybean, maize, and cotton fields.

Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors

“…To obtain novel PPO inhibitors, a series of N -phenyl phthalimides were designed by molecular docking using the mt PPO as a target, and by using Flumioxazin as a lead (Figure 1) [22,23], after which they were synthesized and characterized by NMR and High resolution mass spectrometry (HR-MS). Their herbicidal activities were also evaluated against Brassica campestris ( B. campestris ), Amaranthus retroflexus ( A. retroflexus ) and Digitaria sanguinalis ( D. sanguinalis ) to verify our molecular design strategy.…”

Novel HPPD inhibitors: triketone 2H‐benzo[b][1,4]oxazin‐3(4H)‐one analogs

“…Some, such as compound A (Scheme ), displayed both promising inhibitory activity against protoporphyrinogen oxidase in vitro (IC 50 = 9.50 nM) and excellent herbicidal activity against sensitive plant species at an application rate of 93.75 g/ha. It was also demonstrated that the core structure, 2H ‐1,4‐benzoxazin‐3‐(4 H )‐one, was an important pharmacophore of this PPO herbicide series . As a continuation of our work with this structural motif, we designed a series of novel HPPD inhibitors, 2‐(2 H ‐benzo[ b ] [1,4]oxazine‐7‐carbonyl)cyclohexane‐1,3‐dione analogs ( B ) (Scheme ).…”

“…It was also demonstrated that the core structure, 2H-1,4-benzoxazin-3-(4H)-one, was an important pharmacophore of this PPO herbicide series. [18][19][20] As a continuation of our work with this structural motif, we designed a series of novel HPPD inhibitors, 2-(2H-benzo[b] [1,4]oxazine-7carbonyl)cyclohexane-1,3-dione analogs (B) (Scheme 1). The synthesis, HPPD inhibition and herbicidal activity of these analogs are described.…”

Design and Synthesis of Novel Triazolyl Benzoxazine Derivatives and Evaluation of Their Antiproliferative and Antibacterial Activity

“…Nitrogen-containing heterocyclic compounds have maintained the interest of researchers through decades of historical development of organic synthesis. Among the nitrogen heterocycles, 1,4-benzoxazine is the important scaffold present in various agrochemicals and primarily used by plants as natural defense chemicals [2,3]. In particular, the utility of the 2H-1,4-benzoxazin-3-(4H)-one scaffold as a privileged structure for the generation of drug-like libraries in drug-discovery programs has been amply demonstrated.…”