17359-53-4

Usage

InChI:InChI=1/C9H9NO4/c1-13-5-2-3-6-7(4-5)14-9(12)8(11)10-6/h2-4,9,12H,1H3,(H,10,11)

Upstream product

• 15893-52-4 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one 
• 81066-48-0 7-methoxy-4H-2,3-dioxo-1,4-benzoxazine 
• 55544-88-2 methyl α-(5-methoxy-2-nitrophenoxy)-α-methoxyacetate 
• 704-14-3 3-methoxy-6-nitro-phenol 
• 131761-45-0 2,7-Dimethoxy-2H-1,4-benzoxazin-3(4H)-one 
• 75-08-1 ethanethiol 
• 40925-70-0 2-amino-5-methoxyphenol 

Downstream Products

• 85758-42-5 2-Ethylsulfanyl-2-hydroxy-N-(2-hydroxy-4-methoxy-phenyl)-acetamide 

Relevant academic research and scientific papers

Fate of benzoxazinone allelochemicals in soil after incorporation of wheat and rye sprouts

Growing cereals (especially rye), which are incorporated into the soil to increase soil fertility or organic matter content, is a common practice in crop rotation. The additional sanitizing effect of this incorporation has often been appreciated and is sa

Isolation and synthesis of allelochemicals from gramineae: Benzoxazinones and related compounds

Compounds with a (2H)-1,4-benzoxazin-3(4H)-one skeleton have attracted the attention of phytochemistry researchers since 2,4-dihydroxy-(2H)-1,4-benzoxazin- 3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) were isolated from plants belonging to the Poaceae family. These compounds exhibit interesting biological properties, such as phytotoxic, antimicrobial, antifeedant, antifungal, and insecticidal properties. These chemicals, in addition to a wide variety of related compounds involved in their metabolism, detoxification mechanisms, and degradation on crop soils and other systems, have high interest and in some cases potential agronomic utility. This paper presents a complete review of the methods employed for their synthetic obtention in addition to some of the authors' own contributions to their chemistry. The degradation and phytotoxicity experiments carried out in ongoing research into the potential agronomic utility of these compounds required large amounts of them, which were obtained from natural sources. This paper presents a modified methodology to access DIMBOA from Zea mays cv. Apache and to obtain 2-O-β-D-glucopyranosyl-2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc) and DIBOA from Secale cereale L. New synthetic methodologies were employed for the obtention of the lactams 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)- one and 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and the malonamic acids N-(2-hydroxyphenyl)malonamic acid and N-(2-hydroxy-7-methoxyphenyl)- malonamic acid. The aminophenoxazines 2-amino-7-methoxyphenoxazin-3-one and 2-acetamido-7-methoxyphenoxazin-3-one have been synthesized in the authors' laboratory by novel procedures. All of the methodologies employed allowed the desired compounds to be obtained in high yield and in an easy-to-scale manner.

Structure-activity relationships (SAR) studies of benzoxazinones, their degradation products and analogues. Phytotoxicity on standard target species (STS)

Benzoxazinones 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA) have been considered key compounds for understanding allelopathic phenomena in Gramineae crop plants such as corn (Zea mays L.), wheat (Triticum aestivum L.), and rye (Secale cereale L.). The degradation processes in the environment observed for these compounds, in which soil microbes are directly involved, could affect potential allelopathic activity of these plants. We present in this work a complete structure-activity relationships study based on the phytotoxic effects observed for DIMBOA, DIBOA, and their main degradation products, in addition to several synthetic analogues of them. Their effects were evaluated on standard target species (STS), which include Triticum aestivum L. (wheat) and Allium cepa L. (onion) as monocots and Lepidium sativum L. (cress), Lactuca sativa L. (lettuce), and Lycopersicon esculentum Will, (tomato) as dicots. This permitted us to elucidate their ecological role and to propose new herbicide models based on their structures. The best phytotoxicity results were shown by the degradation chemical 2-aminophenoxazin-3-one (APO) and several 2-deoxy derivatives of natural benzoxazinones, including 4-acetoxy-(2H)-1,4-benzoxazin- 3(4H)-one (ABOA), 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIBOA), and 4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIMBOA). They showed high inhibitory activity over almost all species growth. The fact that APO is a degradation product from DIBOA with high phytotoxicity and stability makes it possible to assign an important ecological role regarding plant defense mechanisms. 2-Deoxy derivatives of natural benzoxazinones display a wide range of activities that allow proposing them as new leads for natural herbicide models with a 1,4-benzoxazine skeleton.

Novel compounds for use in weight loss and appetite suppression in humans

Phenolic compounds with a phenolic molecule to which are covalently linked an oxygen-containing group, a nitrogen or another oxygen containing group, and a C1-C4 alkoxy group, obtainable from monocotyledonous plants, or by chemical synthesis, have been found to act as weight loss agents, appetite suppressants, mood enhancers and adjunctive therapy for arthritis, sleep apnea, fibromyalgia, diabetes and hyperglycemia. Additional chemical compounds of the present invention may include benzoxazinoids-cyclic hydroxyamic acids, lactams, and corresponding glucosides, which may serve as precursors to phenolic compounds. The phenolic compounds and precursors of phenolic compounds of the present invention, at concentrations suitable for human therapeutic use, may be obtained from monocotyledonous plants such as corn in their early growth states which are timely harvested for optimum yield.

An improved synthesis of cyclic hydroxamic acids from Gramineae

The boron trichloride sensitive methoxymethyl (MOM) protecting group has been used to efficiently synthesize polymethoxylated derivatives of the benzoxazinone family of cyclic hydroxamic acids. The MOM group allows the unveiling of the hemiacetal at C-2 of these compounds without demethylating ring methoxy substituents, resulting in greatly increased yields.

A new general approach to the 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one skeleton via diisobutylaluminum hydride reduction of 2,3-dioxo-1,4-benzoxazines

A series of naturally occurring hemiacetals 2a-d was synthesized by the chemoselective diisobutylaluminum hydride reduction of 2,3-dioxo-4H-1,4-benzoxazines 1a,b and their N-hydroxy derivatives 1c,d precursors. The procedure described represents a new general approach to the 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one skeleton giving rise to the bioactive natural hydroxamic acids 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (2c) and 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (2d) in only three steps starting from nitrophenols.

Analogues of the Cyclic Hydroxamic Acid 2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one: Decomposition to Benzoxazolinones and Reaction with β-Mercaptoethanol

Analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-1,4-benzoxazin-3-ones) from Gramineae (Poaceae) have been synthesized by the reductive cyclization of the ring-substituted methyl α-(o-nitrophenoxy)-α-methoxyacetates, followed by demethylation of the C-2 methoxy group with BBr3 or BCl3 to reveal the 2-hydroxy group.A structure-activity series was produced by varying the substituent at C-7 on the aromatic ring .The pKa values for the hydroxamic acid and the phenol moieties were determined for each member of the C-7 series.They correlated well with ? in a linear free energy relationship (LFER) yielding values of ρ = 0.71 (with ?p) for pKa1 (the hydroxamic acid) and ρ = 1.6 (with ρm) for pKa2 (the phenol).A LFER also existed between the rate constants for the unimolecular decomposition of these hydroxamic acids to benzoxazolinones and ?+ (ρ = -1.1).The rates of hydroxamic acid reduction to lactams by β-mercaptoethanol were also investigated.It was found that only compounds with electron-rich aromatic rings and specifically an oxa functionality para to the hydroxamic acid nitrogen atom (compounds 1 and 3 - 5) had measurable rates of reduction. 1H NMR spectra recorded during this reaction in D2O buffers (pD 9), however, showed that compounds 1, 2, 6 - 9 (the only ones investigated) formed a hemithioacetal at C-2 even though only 1 has a measurable rate of reduction by the same thiol.The remarkable rate enhancement provided by an oxa functionality suggests that reduction occurs by direct attack of thiolate on the hydroxamic nitrogen of a resonance-stabilized ion pair.

THE REDUCTION OF 2,4-DIHYDROXY-7-METHOXY-1,4-BENZOXAZIN-3-ONE BY THIOLS

2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), a naturally occurring hydroxamic acid involved in pest resistance of cereals, was reduced by thiols to the corresponding lactam.Kinetic studies showed that the reactive species are undissociated DIMBOA and thiolate anion.Possible mechanisms for the reaction are discussed in the light of relative reactivities of DIMBOA and a compound lacking the 7-methoxy substituent, and results from molecular orbital calculations.Key Word Index - Zea mays; Gramineae; 1,4-benzoxazin-3-one; thiols; reduction.

REACTION OF A CYCLIC HYDROXAMIC ACID FROM GRAMINEAE WITH THIOLS

An insect inhibitor isolated from maize extracts, 2,4- dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), reacted with cysteine, mercaptoethanol, ethanethiol and dithiothreitol.Second order rate constants were 0.54, 0.73 and 1.96 l/mol min for the reaction with cysteine, mercaptoethanol and dithiothreitol, respectively.Products isolated from the reaction of DIMBOA with ethanethiol corresponded to reduction of the hydroxamic acid to amide and/or hemiacetal-hemithioacetal exchange.The reactivity of DIMBOA with sulfhydryl groups of compounds such as cysteine, may be a basis for its inhibitory action on enzymes and its toxicity. - Key Word Index - Zea mays; Gramineae; 1,4-benzoxazin-3-ones; thiols.