WO2014122674A1

WO2014122674A1 - Process for preparation of derivatives of tetrahydrophthalimide

Info

Publication number: WO2014122674A1
Application number: PCT/IN2014/000086
Authority: WO
Inventors: Subhash KADAM; Jegadeesh Thampi; Baburaj KRISHNAN; Rajesh RAJESHIRKE
Original assignee: Rallis India Ltd
Current assignee: Rallis India Ltd
Priority date: 2013-02-08
Filing date: 2014-02-10
Publication date: 2014-08-14
Anticipated expiration: 2015-08-08

Abstract

The present disclosure provides a process for preparation of a compound of formula 1, or isomers or its derivatives thereof, which show a high herbicidal activity against wide variety of weeds. (I) wherein R₁ is a C₃-C₄ alkynyl group, a C₁-C₅ alkyl group, or a C3-C4 alkenyl group, and X is selected from the group consisting of F, Cl, Br, I or H atom.

Description

PROCESS FOR PREPARATION OF DERIVATIVES OF

TETRAHYDROPHTHALIMIDE

TECHNICAL FIELD

[0001] The present disclosure relates to a process for preparation of a derivatives of tetrahydrophthalimide, preferably flumioxazin, N-(7-fluoro-3,4-dihydro-3-oxo-4- prop-2-ynyl-2H-l ,4-benzoxazin-6-yl)cyclohex- 1 -ene-1 ,2-dicarboxamide.

BACKGROUND

[0002] Derivatives of tetrahydrophthalimide are found to have high herbicidal activity against a wide variety of weeds including broad-leaved weeds, graminaceous weeds, commelinaceous weeds and cyperaceous weeds in agricultural plowed field by foliar or soil treatment without producing material phytotoxicity on various agricultural crops such as wheat, barley, corn, soyabean and peanut. Examples of broad-leaved weeds are wild buckwheat (Polygonum convolvulus), ladysthumb (Polygonum persicaria), pale smartweed (Polygonum lapathifolium), common purslane (Portulaca oleraced), common chickweed (Stellaria media), common lambsquarters (Chenopodium album), redroot pigweed (Amaranthus retroflexus), radish (Raphanus sativus), wild mustard (Sinapis arvensis), hemp sesbania (Sesbania exaltata), sicklepod (Cassia obtusifolia), velvetleaf (Abu-tilon theophrastl), prickly sida (Sida spinosa), field pansy (Viola arvensis), catchweed bedstraw (Galium aparine), ivyleaf morningglory (Ipomoea hederacea), tall morn-ingglory (Ipomoea purpurea), henbit (Lamium amplex-icaure), jimsonweed (Datura stramonium), black night-55 shade (Solanum nigrum), persian speedwell (Veronica persica), common cocklebur (Xanthium pensylvanicum), common sunflower (Helianthus annuus), scentless chamomile (Matricaria perforate), pineappleweed (Mat- ricaria matricarioides), oxeye daisy (Chrysanthemum 60 leucanthemum), corn marigold (Chrysanthemum sege- turn), sun spurge. (Euphorbia helioscopia), etc. Examples of graminaceous weeds are Japanese millet (Echino-chloa frumentacea), barnyardgrass (Echinochloa cms- gall), sicklepod (Cassia obtusifolia), large crabgrass 65 (Digitaria sanguinalis), annual bluegrass (Poa annua), blackgrass (Alopecurus myosuroides), oats (Avena sativa), wild oats (Avena fatua), johnsongrass (Sorghum hale pense), etc. Examples of commelinaceous weeds are asiatic dayflower ( Commelina communis), etc. Examples of cyperaceous weeds are yellow nutsedge (Cype-rus esculentus), etc.

[0003] On the pre-emergence soil treatment, the tetrahydrophthalimides exhibit a particularly strong herbicidal activity against broad-leaved weeds such as catchweed bedstraw, common chickweed, field pansy, persian speedwell, scentless chamomile, pale smartweed, ladysthumb, wild mustard, pineappleweed, oxeye daisy, common lambsquarters, black nightshade, field bindweed and redroot pigweed in the field of wheat or barley while exerting no or little chemical injury to wheat or barley; they also exhibit a marked herbicidal activity against broad-leaved weeds such as velvetleaf, common cocklebur, tall morningglory, sickle-pod, prickly sida, jimsonweed, hemp sesbania, redroot pigweed, common lambsquarters and black nightshade in the field of soyabean or peanut while exerting no or little chemical injury to soyabean or peanut.

[0004] Further, some of the derivatives of tetrahydrophthalimide are effective in exterminating the paddy field weeds including graminaceous weeds such as bamyardgrass {Echinochloa oryzicola) and broad-leaved weed such as common falsepimperiiel (Lindernia procumbens), Indian toothcup (Rotala indica) and water- wort (Elatine triandra) without any phytotoxicity to rice plants on flooding treatment.

[0005] The tetrahydrophthalimides act against broad-leaved weeds and grass weeds in crops such as wheat, rice, maize, soya and cotton without causing any significant damage to the crop plants.

[0006] The tetrahydrophthalimides can be applied pre-, post- emergence or pre- plant, or together with the seed of a crop plant. It is also possible to apply the tetrahydrophthalimides by applying seeds, pretreated with the tetrahydrophthalimides, of a crop plant. If the tetrahydrophthalimides are less well tolerated by certain crop plants, application technique may be used where tetrahydrophthalimides are sprayed, with spraying equipment, in such a way that tetrahydrophthalimides do not come into contact with the leaves of the sensitive crop plants, while the tetrahydrophthalimides reach the leaves of undesirable plants.

[0007] One type of tetrahydrophthalimides is flumioxazin or N-(7-fluoro-3,4- dihydro-3 -oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide, which is well known and has been found to be particularly useful as pre=emergent herbicides when used against sensitive weeds. Flumioxazin is useful in controlling undesired vegetation in crops of useful plants, for example, monocotyledon crop plants, such as cereal crops, rice, corn, potatoes and sugar cane.

[0008] Dicarboximide herbicides are well known in the art as being highly beneficial for controlling undesirable vegetation in agronomically desirable crops including corn, cereals such as wheat and barley. They work on a broad range of grasses and broad leaf weeds, but not on crops they are designed to protect. Crops like rice, wheat, barley, soybean, maize, and many others are able to metabolize dicarboximide effectively.

[0009] The tetrahydrophthalimides are known in art and can be prepared in a number of different ways.

[00010] US Patent No. 4,431,822 discloses a compound of formula 1 and its process of preparation.

sopropy - wherein X is chlorine atom or bromine atom

[00011] Compound of formula 1 was reported to be prepared by reacting 4-chloro- 2-fluoro-5-isopropoxyaniline and 3,4,5,6-tetrahydrophthalic anhydride with acetic acid till it dissolves and then refluxed for 3 hours, which after completion was cooled and extracted using ether and washed with water.

[00012] US Patent No. 4,938,795 discloses preparation of tetrahydrophthalimide herbicicdes

wherein R is methyl or n-pentyl group

using 2-chloro-4-fluoro-5-amino phenol and 3,4,5,6-tetrahydrophthalic anhydride with acetic acid and refluxed for 2 hours. The product obtained was then added to the solution of sodium hydroxide in water and methyl chloroformate . \ [00013] US Patent No. 4,736,068 discloses a process of preparation of tetrahydrophthalimides by reacting hydroxyphenyltetrahydrophthalimide with halide in presence of base and an inert solvent at 40° - 90° C with molar ratio of hydroxyphenylphmalim.de and halide is from 1 : 1 to 1 :1.1.

[00014] US Patent Application No. 2012/214668 discloses a compound of formula la and its process for preparation.

[00015] Compound of formula I was reported to be prepared by reacting phthalic anhydride with a compound of formula Ilia.

[00016] The need exists, however, for newer process for preparing these herbicides, like flumioxazin which destroy or reward weeds without causing significant damage to the concerned crops.

SUMMARY

[00017] The present disclosure relates a process for preparation of a compound of formula 1 , or isomers or its derivatives thereof,

Formula 1

wherein: Ri is selected from a C3-C₄ alkynyl group, a C₁-C5 alkyl group, or a C₃-C alkenyl group; X is selected from the group consisting of F, CI , Br, I or H atom; said process comprising :

treating a compound of formula 2

Formula 2

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

with a halo ester, in the presence of a polar solvent and a base to obtain a compound of formula 3;

Formula 3

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

R" is selected from C₁-C5 alkyl group;

treating the compound of formula 3 with an acid and a reducing agent to obtain a compound of formula 4;

Formula 4

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 4 with a mineral acid or a mixture of mineral acid to obtain a compound of formula 5;

Formula 5

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 5 with a reagent in presence of a base and a polar solvent to obtain a compound of formula 6;

Formula 6

wherein: Ri is selected from a C₃-C₄ alkynyl group, a C₁-C5 alkyl group, or a C3-C₄ alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom; treating the compound of formula 6 with an acid and a reducing agent to obtain a compound of formula 7; and

Formula 7

wherein: Ri is selected from a C3-C4 alkynyl group, a C₁-C5 alkyl group, or a C3-C4 alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom; treating the compound of formula 7 with acetic acid and acid anhydride to obtain a compound of fo f.

Formula 1

[00018] The derivatives of tetrahydrophthalimide show a high herbicidal activity against a wide variety of weeds.

[00019] These and other features, aspects, and advantages of the present disclosure will become better understood with reference to the following description. This statement is provided to introduce a selection of concepts in simplified form.

DETAILED DESCRIPTION

Definitions

[00020] The present disclosure will be described more fully hereinafter. Indeed, the invention can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. As used in the specification, and in the appended claims, the singular forms "a", "an", "the", include plural referents unless the context clearly dictates otherwise.

[00021] In the structural formula given herein and throughout the present disclosure, the following terms have the indicated meaning, unless specifically stated otherwise.

[00022] The term "C1 -C5 alkyl" refers to a monoradical branched or unbranched saturated hydrocarbon chain having 1, 2, 3, 4, or 5 carbon atoms. This term is exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butylj n-pentyl, and the like.

[00023] The term "C3-C4 alkynyl" refers to a monoradical of an unsaturated hydrocarbon chain having 3 or 4 carbon atoms. This term is exemplified by groups such as propargyl (or prop-l-yn-3-yl), homopropargyl (or but-l-yn-4-yl).

[00024] The term "C3-C4 alkenyl" refers to a monoradical of a branched or unbranched unsaturated hydrocarbon chain having 3 or 4 carbon atoms. This term is exemplified by groups such as allyl, isopropylene, butylene or isobutylene.

[00025] "Halo" or "Halogen", alone or in combination with any other term means halogens such as chloro (CI), bromo (Br), fluoro (F) and iodo (I).

[00026] The term "seed" comprises seed of all types, such as, for example, corns, fruits, tubers, seedlings and similar forms.

[00027] The compounds described herein may may exist as isomers, (i.e., structural isomers), regioisomers, or enantiomers. Accordingly, the chemical structures depicted herein encompass all possible enantiomers of the illustrated or identified compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically.

[00028] The present disclosure provides tetrahydrophthalimides, its isomers, derivatives thereof, which are useful intermediate in the preparation of herbicidal sulfonamide. The novel intermediates are useful either as an active ingredient for agrochemical, especially as herbicides or act as precursors for the synthesis of active ingredients.

[00029] The present disclosure provides a process for the preparation of herbicidal phthalimid, flumioxazin or its isomers, and other derivatives thereof. Flumioxazin is useful as an active agrochemical ingredient, especially herbicides.

[00030] Flumioxazin or its isomers, and other derivatives thereof may be used as a foliar, or soil applied herbicides suitable for the control of many annual and perennial broadleaves species in cereals, grains, corn, sugarcane and other crops and vine control in pasture and crop land, and can also be used in pre-plant or pre-emergence applications.

[00031] Accordingly, the present disclosure provides a process for preparation process for preparation of a compound of formula 1, or isomers or its derivatives thereof,

Formula 1

wherein: Ri is selected from a C3-C4 alkynyl group, a C₁-C5 alkyl group, or a C₃ alkenyl group; X is selected from the group consisting of F, CI , Br, I or H atom; said process comprising :

treating a compound of formula 2

Formula 2

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

Formula 3

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

R" is selected from C₁-C₅ alkyl group; treating the compound of formula 3 with an acid and a reducing agent to obtain a compound of formula 4;

Formula 4

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 4 with a mineral acid or a mixture of mineral acids to obtain a compo

Formula 5

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

Formula 6

wherein: Ri is selected from a C₃-C4 alkynyl group, a Ci-C₅ alkyl group, or a C3-C4 alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 6 with an acid and a reducing agent to obtain a compound of formula 7; and

Formula 7 wherein: R_\ is selected from a C3-C4 alkynyl group, a C1-C5 alkyl group, or a C3-C4 alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 7 with acetic acid and acid anhydride to obtain a compound of f.

Formula 1

[00032] An embodiment of the present disclosure provides a process for preparation of a compound of formula 1, or isomers or its derivatives thereof.

Formula 1

wherein: Ri is selected from a C3-C4 alkynyl group, a C1-C5 alkyl group, or a alkenyl group; X is selected from the group consisting of F, CI , Br, I or H atom; said process comprising :

treating a compound of formula 2

Formula 2

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

Formula 3

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

R" is selected from C1-C5 alkyl group;

Formula 4

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 4 with a mineral acid or a mixture mineral acids to obtain a comp

Formula 5

wherein: X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 5 with a reagent in presence of a base and a polar solvent to obtain a comp

Formula 6

wherein: Ri is selected from a C3-C4 alkynyl group, a C1-C5 alkyl group, or a C3-C4 alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom; treating the compound of formula 6 with a acid and a reducing agent to obtain a compound of formula 7; and

Formula 7

wherein: Ri is selected from a C₃-C₄ alkynyl group, a C₁-C5 alkyl group, or a C₃-C₄ alkenyl group; and X is selected from the group consisting of F, CI, Br, I or H atom; treating the compound of formula 7 with acetic acid and acid anhydride to obtain a compound of f.

Formula 1

[00033] In accordance with the present disclosure, the base is selected from an alkali metal carbonate base selected from the group consisting of potassium carbonate, cesium carbonate, sodium carbonate or sodium bicarbonate or an alkali metal hydroxide base selected from the group consisting of sodium hydroxide, potassium hydroxide or lithium hydroxide or an organic base selected from the group consisting of triethyl amine, di-isopropyl amine, di-isopropyl ethyl amine or pyrrolidine.

[00034] The halo ester used in the present disclosure is suitably selected from methyl bromo acetate, ethyl bromo acetate, propyl bromo acetate, butyl bromo acetate, or tert-butyl bromo acetate.

[00035] The polar solvent used in the reactions of the present disclosure is selected from acetone, acetonitrile, Ν,Ν-dimethylformamide, dichloromethane, methanol, tetrahydrofuran or water.

[00036] In accordance with the present disclosure, the mineral acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.

[00037] The reagent used in the present disclosure is selected from a halo C₃-C₄ alkynyl group, a halo C₁-C5 alkyl group, or a halo C₃-C₄ alkenyl group.

[00038] The halo group is selected from the group consisting of F, CI, Br and I. [00039] In one aspect of the present disclosure, the acid anhydride is 3,4,5,6- tetrahydrophthalic anhydride.

[00040] In another aspect of the present disclosure, the acid is acetic acid.

[00041] The reducing agent used in the present disclosure is selected from iron powder, lithium aluminium hydride, or sodium borohydride.

[00042] In one aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is in the range of 2.0 - 4 mol% of compound with formula 6. In one of the embodiment, the amount of reducing agent used to obtain the compound of formula 7 is in the range of 2.2 - 3.1 mol% of compound with formula 6.

[00043] In another aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is of 2.2 mol% of compound with formula 6.

[00044] In one aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is 2.5 mol% of compound with formula 6.

[00045] In another aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is 3.0 mol% of compound with formula 6.

[00046] In yet another aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is 3.1 mol% of compound with formula 6.

[00047] In one aspect of the present disclosure, the amount of reducing agent used to obtain the compound of formula 7 is 4 mol% of compound with formula 6.

[00048] Another embodiment of the present disclosure provides a process for preparation of flumioxazin, or isomers or its derivatives thereof comprising:

coupling 5-fluoro-2-nitrophenol with ethyl bromo acetate, in the presence of acetone and potassium carbonate to obtain ethyl-2-(2-amino-5-fluorophenoxy)acetate; cyclising ethyl-2-(2-amino-5-fluorophenoxy)acetate with acetic acid, ethyl acetate and iron powder to obtain 7-fluoro-2H-l,4-benzoxazin-3(4H)-one;

nitrating 7-fluoro-2H-l,4-benzoxazin-3(4H)-one with sulphuric acid and nitric acid to obtain 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one;

coupling 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one with propargyl bromide, in presence of potassium carbonate and acetone to obtain 6-nitro-7-fluoro-4- prop-2-ynyl-l,4-benzoxazin-3-one; reducing 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with 2.2 mol% of iron powder, acetic acid and ethyl acetate to obtain 6-amino-7-fluoro-4-prop-2- ynyl-l,4-benzoxazin-3-one; and

treating 6-amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with acetic acid and 3,4,5,6-tetrahydrophthalic anhydride to obtain flumioxazin.

[00049] Yet another embodiment of the present disclosure provides a process for preparation of flumioxazin, isomers and other derivatives thereof comprising:

coupling 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one with propargyl bromide, in presence of potassium carbonate and acetone to obtain 6-nitro-7-fluoro-4- prop-2-ynyl- 1 ,4-benzoxazin-3-one;

reducing 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with 3.0 mol% of iron powder, acetic acid and ethyl acetate to obtain 6-amino-7-fluoro-4-prop-2- ynyl-l,4-benzoxazin-3-one; and

[00050] Further an embodiment of the present disclosure provides a process for preparation of flumioxazin, isomers and other derivatives thereof comprising:

coupling 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one with propargyl bromide, in presence of potassium carbonate and acetone to obtain 6-nitro-7-fluoro-4- prop-2-ynyl- 1 ,4-benzoxazin-3 -one; reducing 6-nitro-7-fluoro-4-prop-2-yny ,4-benzoxazin-3-one with 3.1 mol% of iron powder, acetic acid and ethyl acetate to obtain 6-amino-7-fiuoro-4-prop-2- ynyl-l,4-benzoxazin-3-one; and

treating 6-amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with acetic acid and 3,4,5, 6-tetrahydrophthalic anhydride to obtain flumioxazin.

[00051] The compound of formula I, isomers and other derivatives thereof, may be prepared as outlined in the Schemes.

[00052] Scheme 1: General route for the synthesis of compounds of formula 1, isomers and other derivatives thereof.

[00053] A compound of formula 2 is reacted with a halo ester selected from methyl bromo acetate, ethyl bromo acetate, propyl bromo acetate, butyl bromo acetate, tert- butyl bromo acetate, a polar solvent selected from acetone, acetonitrile, N,N- dimethylformamide, dichloromethane, methanol, tetrahydrofuran or water and a base selected from an alkali metal carbonate base selected from the group consisting of potassium carbonate, cesium carbonate, sodium carbonate or sodium bicarbonate or an alkali metal hydroxide base selected from the group consisting of sodium hydroxide, potassium hydroxide or lithium hydroxide or an organic base selected from the group consisting of triethyl amine, di-isopropyl amine, di-isopropyl ethyl amine or pyrrolidine to obtain a compound of formula 3,

[00054] Treating the compound of formula 3 with acetic acid and a reducing agent selected from iron powder, lithium aluminium hydride, or sodium borohydride to obtain a compound of formula 4. [00055] The compound of formula 4 is converted to a compound of formula 5 by treatment mineral acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid.

[00056] Compound of formula 5 is further converted to a compound of formula 6 by treating with a base selected from an alkali metal carbonate base selected from the group consisting of potassium carbonate, cesium carbonate, sodium carbonate or sodium bicarbonate or an alkali metal hydroxide base selected from the group consisting of sodium hydroxide, potassium hydroxide or lithium hydroxide or an organic base selected from the group consisting of triethyl amine, di-isopropyl amine, di-isopropyl ethyl amine or pyrrolidine and a polar solvent selected from acetone, acetonitrile, Ν,Ν-dimethylforrnarnide, dichloromethane, methanol, tetrahydrofuran or water.

[00057] The compound of formula 6 is reacted with acetic acid and a reducing agent selected from iron powder, lithium aluminium hydride, or sodium borohydride to obtain a compound of formula 7.

[00058] Treating the compound of formula 7 with acetic acid and acid anhydride to obtain a compound of formula 1, isomers and other derivatives.

[00059] In the compounds of formula 1, 3, 6, 7 above, Ri is selected from a C3-C4 alkynyl group, a C1-C5 alkyl group, a C3-C4 alkenyl group; X is selected from the group consisting of F, CI , Br, I or H atom; R is selected from C1-C5 alkyl group.

Abbreviations

[00060] The following abbreviations are employed in the description:

K2CO3: Potassium carbonate;

Fe: Iron Powder;

HN0₃: Nitric acid;

H2SO4: Sulfuric acid;

H: Hydrogen;

F: Fluoro;

CI: Chloro;

Br: Bromo;

I: Iodo;

RT: Room temperature.

Examples [00061] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure.

[00062] All isomers of the compounds of the instant disclosure are contemplated, either in admixture or in pure or substantially pure form.

[00063] Preparation of Example 1: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl- 2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide

Step 1: Ethyl-2-(2-nitro-5-fluorophenoxy)acetate

[00064] 5-Fluoro-2-nitrophenol (50.0 gm , 0.32 moles) was dissolved in acetone (500 mL) at ambient temperature followed by potassium carbonate (175.9 gm, 0.63 mol).The reaction mixture was allowed to stir and ethyl bromo acetate (63.6 gm, 0.38 moles) was added. The above reaction mixture was refluxed under nitrogen atmosphere. The reaction was monitored by HPLC. After completion of the reaction, acetone was evaporated, and the residue was then quenched with water and extracted using ethyl acetate (2x250 mL) and washed with brine. The organic layer was collected and dried over sodium sulphate and concentrated to obtain the crude product as yellow oil, ethyl-2-(2-nitro-5-fluorophenoxy) acetate.

Dry wt : 75 gm

Yield : 97%

HPLC purity : 98.5%

MP : low melting solid

Step 2: 7-Fluoro-2H-l,4-benzoxazin-3(4H)-one

[00065] A solution of 5% acetic acid (340 mL) and iron powder (172.5 gm) was stirred and heated to 70°C. A mixture of acetic acid (300 mL), ethyl-2-(2-nitro-5- fluorophenoxy) acetate (75 gm, 0.308 mol) and ethyl acetate (300 mL) were added drop wise to the above solution at 70°C over a period of 45 min and the reaction mixture was allowed to stir for 1 h. The reaction was monitored by HPLC. After completion of reaction, the reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (3 x 50 mL) at 40°C and allowed to stir for 30 mins. Organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to afford crude product which was purified by preparative HPLC to give pure product as white solid, 7-fluoro-2H-l,4- benzoxazin-3(4H)-one. Dry wt. : 36.5 gm

Yield ; 70.7%

HPLC Purity : 99.2%

Step 3: 6-Nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one

[00066] A mixture of 7-fluoro-2H-l,4-benzoxazin-3(4H)-one (35 gm, 0.209 mol) and 80% sulphuric acid (525 mL) was cooled to 0°C. 70% nitric acid was added dropwise to the above mixture for over a period of 45-60 mins. The reaction mixture was stirred for 1 hr at 0°C and monitored by HPLC. After completion of reaction, the reaction mixture was slowly quenched with water at 0-5°C and stirred well till dense solid appeared. The reaction mixture was then filtered and washed with water. The solid 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one obtained was dried under vacuum at 55-60°C for 8 h at 500 mm of Hg.

Dry wt. : 36 gm

Yield : 81%

HPLC Purity : 92.5%

Step 4: 6-Nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one

[00067] A mixture of 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one (35 gm, 0.209 mpl) and acetone (1.05 L) was stirred. To the reaction mixture potassium carbonate (29.6 gm) and propargyl bromide (24.5 gm) at ambient temperature under nitrogen atmosphere. The above reaction mixture was then heated to 50°c for 3 h and the progress of the reaction was monitored by HPLC. After completion of reaction, acetone was evaporated completely and to the residue petroleum ether is added and stirred for 1 hr. The solid was filtered and washed with petroleum ether. The solid 6- nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was dried over vacuum.

Dry wt. : 37g

Yield : 89%

HPLC Purity : 92.7%

Step 5: 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one

[00068] To the solution of 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one (3.0 g, 0.012 mol%) in acetic acid (12.0 ml ) and ethyl acetate (12.0 ml), iron powder (1.5 g, 2.2 mol %) was added to the reaction mixture at 70°C under nitrogen atmosphere. The reaction mixture was allowed to stir at 70°C for lhr and the reaction mixture was monitored by HPLC. After completion of reaction, water and ethyl acetate were added to reaction mixture and stirred for 30 min. The organic layer was washed with saturated sodium bicarbonate solution and brine solution. The organic layer was dried over sodium sulphate and concentrated to obtain yellow solid product, 6-amino-7-fluoro-4-prop-2-ynyl- 1 ,4-benzoxazin-3-one.

Dry wt. : 2.3 g

Yield : 90.0 %

HPLC Purity : 94.5 %

[00069] 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was also obtained by the process as described in step 5 using lithium aluminium hydride or sodium borohydride.

Step 6: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4-benzoxazin-6- yl)cyclohex-l -ene-1 ,2-dicarboxamide

[00070] A mixture of 6-amino-7-fluoro-4(2-propynyl)-2H-l,4-benzoxazin-3(4H)- one (15 g, 0.068 moles), and acetic acid (225.0 ml, 15.0 rel. vol.) was stirred. To the above reaction mixture, 3,4,5, 6-tetrahydrophthalic anhydride (13.4 g) was added and the reaction mixture was stirred at 80° C for 6 hours and the progress of the reaction was monitored by HPLC. After completion of reaction, the reaction mixture was cooled to ambient temperature and slowly added to water and stirred well to obtain dense solid. The solid was then filtered and washed with water. The solid was dried over high vacuum at 55°C for 8 hr to obtain off white solid product, N-(7-fluoro-3,4- dihydro-3 -oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

Dry wt. 19.0 g

Yield 78.6 % .

HPLC Purity 95.8 %

[00071] Example 2: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4- benzoxazin-6-yl)cyclohex-l-ene-l,2-dicarboxamide

Step 1: Ethyl-2-(2-nitro-5-fluorophenoxy)acetate

[00072] Ethyl-2-(2-nitro-5-fluorophenoxy)acetate was obtained by the process as described in step 1 of example 1.

Step 2: 7-Fluoro-2H-l,4-benzoxazin-3(4H)-one

[00073] 7-Fluoro-2H-l,4-benzoxazin-3(4H)-one was obtained by the process as described in step 2 of example 1. Step 3: 6-Nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one

[00074] 6-Nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one was obtained by the process as described in step 3 of example 1.

Step 4: 6-Nitro-7-fluoro-4-prop-2-yhyl-l,4-benzoxazin-3-one

[00075] 6-Nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was obtained by the process as described in step 4 of example 1.

Step 5: 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one

[00076] To the solution of 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one (17 g, 0.068 moles) in acetic acid (70 mL) and ethyl acetate (70 mL) iron powder (11.3 g, 3.0 mol %) was added to the reaction mixture at 70°C under nitrogen atmosphere. The reaction mixture was allowed to stir at 70°C for lhr and the reaction mixture was monitored by HPLC. After completion of reaction, water and ethyl acetate were added to reaction mixture and stirred for 30 min. The organic layer was washed with saturated sodium bicarbonate solution and brine solution. The organic layer was dried over sodium sulphate and concentrated to obtain yellow solid product, 6-amino-7- fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one.

Dry wt. : 13. lg

Yield : 87%

HPLC Purity : 93.3%

[00077] 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was also obtained by the process as described in step 5 using lithium aluminium hydride or sodium borohydride.

Step 6: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide

[00078] A mixture of 6-amino-7-fluoro-4(2-propynyl)-2H-l,4-benzoxazin-3(4H)- one (15 g, 0.068 moles), and acetic acid (225 mL, 15.0 rel. vol.) was stirred. To the above reaction mixture, 3,4,5,6-tetrahydrophthalic anhydride (13.4 g) was added and the reaction mixture was stirred at 80° C for 6 hours and the progress of the reaction was monitored by HPLC- After completion of reaction, the reaction mixture was cooled to ambient temperature and slowly added to water and stirred well to obtain dense solid. The solid was then filtered and washed with water. The solid was dried over high vacuum at 55°C for 8 hr to obtain off white solid product, N-(7-fluoro-3,4- dihydro-3 -oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

Dry wt. : 19 g

Yield : 78.6%

HPLC Purity : 95.8%

[00079] Example 3: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4- benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide

Step 1: Ethyl-2-(2-nitro-5-fiuorophenoxy)acetate

[00080] Ethyl-2-(2-nitro-5-fluorophenoxy)acetate was obtained by the process as described in step 1 of example 1.

Step 2: 7-Fluoro-2H-l,4-benzoxazin-3(4H)-one

[00081] 7-Fluoro-2H-l,4-benzoxazin-3(4H)-one was obtained by the process as described in step 2 of example 1.

Step 3: 6-Nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one

[00082] 6-Nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one was obtained by the process as described in step 3 of example 1.

Step 4: 6-Nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one

[00083] 6-Nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was obtained by the process as described in step 4 of example 1.

Step 5: 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one

[00084] To the solution of 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one (20.0 g, 0.08 mol%) in acetic acid (80.0 ml) and ethyl acetate (80.0 ml), iron powder (14.0 g, 3.1 mol %) was added to the reaction mixture at 70°C under nitrogen atmosphere. The reaction mixture was allowed to stir at 70°C for lhr and the reaction mixture was monitored by HPLC. After completion of reaction, water and ethyl acetate were added to reaction mixture and stirred for 30 min. The organic layer was washed with saturated sodium bicarbonate solution and brine solution. The organic layer was dried over sodium sulphate and concentrated to obtain yellow solid product, 6-amino-7-fluoro-4-prop-2-ynyl- 1 ,4-benzoxazin-3-one.

Dry wt. : 15.5 g

Yield : 85.0 %

HPLC Purity : 92.3 % [00085] 6-Amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one was obtained by the process as described in step 5 using lithium aluminium hydride or sodium borohydride.

Step 6: N-(7-Fluoro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l ,4-benzoxazin-6- yl)cyclohex-l-ene-l,2-dicarboxamide

[00086] A mixture of 6-amino-7-fluoro-4(2-propynyl)-2H-l,4-benzoxazin-3(4H)- one (15 g, 0.068 moles), and acetic acid (225.0 ml, 15 rel. vol.) was stirred. To the above reaction mixture, 3,4,5,6-tetrahydrophthalic anhydride (13.4 g) was added and the reaction mixture was stirred at 80° C for 6 hours and the progress of the reaction was monitored by HPLC. After completion of reaction, the reaction mixture was cooled to ambient temperature and slowly added to water and stirred well to obtain dense solid. The solid was then filtered and washed with water. The solid was dried over high vacuum at 55°C for 8 hr to obtain off white solid product, N-(7-fiuoro-3,4- dihydro-3 -oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

Dry wt. : 19.0 g

Yield : 78.6 %

HPLC Purity : 95.8 %

[00087] Compounds 4-75 were prepared by following the experimental procedure of Example 1, 2 or 3 using appropriate intermediates.

N-(7-Chloro-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene-l,2-dicarboxamide.

N-(7-Bromo-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3,4-dihydro-3-oxo-4-prop-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(3 ,4-Dihydro-3 -oxo-4-prop-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-ethyl-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene-l,2- dicarboxamide.

N-(7-Fluoro-3 ,4-dihydro-3-oxo-4-propyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide. N-(4-Butyl-7-fluoro-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1,2- dicarboxamide.

N-(4-But-2-ynyl-7-fluoro-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(4-But-2-enyl-7-fluoro-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(4-But-2-ynyl-7-fluoro-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3 ,4-dihydro-3 -oxo-4-pentyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1,2-dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-pent-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-pent-2-enyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-pent-3-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1,2-dicarboxamide.

N-(7-Fluoro-3 ,4-dihydro-3-oxo-4-pent-3 -enyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene- 1 ,2-dicarboxamide.

N-(4-5ec-Butyl-7-fluoro-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1,2-dicarboxamide.

N-(4-wo-Butyl-7-fluoro-3 ,4-dihydro-3 -oxo)-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3 ,4-dihydro-3 -oxo-4-( 1 -methyl-butyl)-2H- 1 ,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-(2-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Fluoro-3,4-dihydro-3-oxo-4-(3-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene-1 ,2-dicarboxamide.

l-[7-Fluoro-4-(l-methyl-butyl)-3-oxo-3,4-dihydro-2H-benzo[l,4]oxazin-6-yl]- pyrrole-2,5-dione

N-(7-Chloro-3,4-dihydro-3-oxo-4-ethyl-2H-l ,4-benzoxazin-6-yl)cyclohex-l -ene-1 ,2- dicarboxamide. N-(7-Chloro-3,4-dihydro-3-oxo-4-propyl-2H-l ,4-benzoxazin-6-yl)cyclohex-l -ene- 1 ,2-dicarboxamide.

N-(4-Butyl-7-chloro-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(4-But-2-ynyl-7-chloro-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene-1 ,2-dicarboxamide.

N-(4-But-2-enyl-7-chloro-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(4-But-2-ynyl-7-chloro-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene-l,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-pentyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-pent-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-pent-2-enyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene-1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-pent-3-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-pent-3-enyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene-l,2-dicarboxamide.

N-(4-iec-Butyl-7-chloro-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(4-wo-Butyl-7-chloro-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-(l-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-(2-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex-l -ene-1 ,2-dicarboxamide.

N-(7-Chloro-3,4-dihydro-3-oxo-4-(3-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex-l-ene-l,2-dicarboxamide.

1 -[7-Chloro-4-( 1 -methyl-butyl)-3-oxo-3,4-dihydro-2H-benzo[ 1 ,4]oxazin-6-yl]- pyrrole-2 ,5 -dione N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-ethyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-propyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1,2- dicarboxamide.

N-(4-Butyl-7-iodo-3 ,4-dihydro-3-oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(4-But-2-ynyl-7-iodo-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(4-But-2-enyl-7-iodo-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(4-But-2-ynyl-7-iodo-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3-oxo-4-pentyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-pent-2-ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-pent-2-enyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-pent-3 -ynyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-pent-3-enyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(4-5ec-Butyl-7-iodo-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(4-wo-Butyl-7-iodo-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l-ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-( 1 -methyl-butyl)-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-(2-methyl-butyl)-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1,2-dicarboxamide.

N-(7-Iodo-3 ,4-dihydro-3 -oxo-4-(3 -methyl-butyl)-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide. 1 -[7-Iodo-4-(l -methyl-butyl)-3-oxo-3,4-dihydro-2H-benzo[ 1 ,4]oxazin-6-yl]-pyrrole- 2,5-dione

N-(7-Bromo-3 ,4-dihydro-3 -oxo-4-ethyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(7-Bromo-3 ,4-dihydro-3-oxo-4-propyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(4-Butyl-7-bromo-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2- dicarboxamide.

N-(4-But-2-ynyl-7-bromo-3,4-dihydro-3-oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene-l,2-dicarboxamide.

N-(4-But-2-enyl-7-bromo-3 ,4-dihydro-3 -oxo-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene- 1 ,2-dicarboxamide.

N-(4-But-2-ynyl-7-bromo-3,4-dihydro-3-oxo-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(7-Bromo-3 ,4-dihydro-3 -oxo-4-pentyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Bromo-3,4-dihydro-3-oxo-4-pent-2-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxarriide.

N-(7-Bromo-3 ,4-dihydro-3 -oxo-4-pent-2-enyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene-l,2-dicarboxamide.

N-(7-Bromo-3,4-dihydro-3-oxo-4-pent-3-ynyl-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene-l,2-dicarboxamide.

N-(7-Bromo-3 ,4-dihydro-3 -oxo-4-pent-3-enyl-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 - ene- 1 ,2-dicarboxamide.

N-(4-5ec-Butyl-7-bromo-3,4-dihydro-3-oxo)-2H-l,4-benzoxazin-6-yl)cyclohex-l- ene- 1 ,2-dicarboxamide.

N-(4-zso-Butyl-7-bromo-3,4-dihydro-3-oxo)-2H- 1 ,4-benzoxazin-6-yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Bromo-3,4-dihydro-3-oxo-4-(l-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

N-(7-Bromo-3,4-dihydro-3-oxo-4-(2-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide. N-(7-Bromo-3,4-dihydro-3-oxo-4-(3-methyl-butyl)-2H-l,4-benzoxazin-6- yl)cyclohex- 1 -ene- 1 ,2-dicarboxamide.

1 - [ 7-Bromo-4-( 1 -methyl-butyl)-3 -oxo-3 ,4-dihydro-2H-benzo[ 1,4] oxazin-6-yl] - pyrrole-2,5-dione

[00088] Flumioxazin prepared by the process of the present disclosure may be in the form of a off-white crystalline solid free from visible extraneous matter, particulate solids, and granules of varying particle size, wettable powders or dusts.

[00089] The compound can also be formulated as water soluble wettable powders (WP), water dispersible granules (WDG), water emulsifiable granules (WEG), suspoemulsion (SE) or oil suspension concentrate (SC). It may be applied to a field in the form of a liquid spray, or as solid powder or granules.

[00090] Although the subject matter has been described in considerable detail with reference to certain preferred embodiments thereof, other embodiments are possible. As such, the spirit and scope of the present disclosure should not be limited to the description of the preferred embodiment contained therein.

Claims

I/We Claim:

1. A process for preparing a compound of formula 1 , or isomers or its derivatives thereof ,

Formula 1

wherein:

R] is selected from a C3-C4 alkynyl group, a C1-C5 alkyl group, or a C3-C₄ alkenyl group;

X is selected from the group consisting of F, CI , Br, I or H atom;

said process comprising :

treating a compound of formula 2

Formula 2

wherein : X is selected from the group consisting of F, CI, Br, I or H atom; with a halo ester, in the presence of polar solvent and a base to obtain compound of formula 3;

Formula 3

wherein :

X is selected from the group consisting of F, CI, Br, I or H atom;

R is selected from CI -C5 alkyl group; treating the compound of formula 3 with a acid and a reducing agent to obtain a compound of formula 4;

Formula 4

wherein :

X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 4 with a mineral acids or a mixture of mineral acids to obtain a compound of formula 5;

Formula 5

wherein : .

X is selected from the group consisting of F, CI, Br, I or H atom;

Formula 6

wherein :

Ri is selected from a C₃-C₄ alkynyl group, a Ci-C₅ alkyl group, C₃-C₄ alkenyl group;

X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 6 with a acid and a reducing agent to obtain a compo

Formula 7

wherein :

X is selected from the group consisting of F, CI, Br, I or H atom;

treating the compound of formula 7 with acetic acid and acid anhydride to obtain a compound of formula 1, isomers and other derivatives.

Formula 1

The process as claimed in claim 1 , wherein the base is selected from an alkali metal carbonate base selected from the group consisting of potassium carbonate, cesium carbonate, sodium carbonate and sodium bicarbonate or an alkali metal hydroxide base selected from the group consisting of sodium hydroxide, potassium hydroxide or lithium hydroxide or an organic base such as triethyl amine, di-isopropyl amine, di-isopropyl ethyl amine or pyrrolidine. The process as claimed in claim 1, wherein the halo ester is selected from methyl bromo acetate, ethyl bromo acetate, propyl bromo acetate, butyl bromo acetate, or tert-butyl bromo acetate.

The process as claimed in claim 1, wherein the polar solvent is selected from acetone, acetonitrile, Ν,Ν-dimethylformamide, dichloromethane, methanol, tetrahydrofuran or water.

The process as claimed in claim 1, wherein the mineral acid is selected from group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid and nitric acid.

The process as claimed in claim 1 , wherein the reagent is selected from a halo C₃-C₄ alkynyl group, a halo C)-C₅ alkyl group, a halo C₃-C₄ alkenyl group. The process as claimed in claim 6, wherein the halo group is selected from the group consisting of F, CI, Br, and I.

The process as claimed in claim 1, wherein the acid anhydride is 3,4,5,6- tetrahydrophthalic anhydride.

9. The process as claimed in claim 1, wherein the acid is acetic acid.

10. The process as claimed in claim 1, wherein the reducing agent is selected from iron powder, lithium aluminium hydride, or sodium borohydride.

11. The process as claimed in claim 1, wherein the amount of reducing agent used to obtain the compound of formula 7 is in the range of 2.2 - 3.1 mol% of compound with formula 6.

12. A process for preparation of flumioxazin, or isomers or its derivatives thereof comprising:

coupling 5-fluoro-2-nitrophenol with ethyl bromo acetate, in the presence of acetone and potassium carbonate to obtain ethyl-2-(2-amino-5- fluorophenoxy)acetate;

cyclising ethyl-2-(2-amino-5-fluorophenoxy)acetate with acetic acid, ethyl acetate and iron powder to obtain 7-fluoro-2H-l,4-benzoxazin-3(4H)- one;

nitrating 7-fluoro-2H-l,4-benzoxazin-3(4H)-one with sulphuric acid and nitric acid to obtain 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one; coupling 6-nitro-7-fluoro-2H-l,4-benoxazin-3(4H)-one with propargyl bromide, in presence of potassium carbonate and acetone to obtain 6-nitro-7- fluoro-4-prop-2-ynyl- 1 ,4-benzoxazin-3-one;

reducing 6-nitro-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with 2.2 mol% of iron powder, acetic acid and ethyl acetate to obtain 6-amino-7-fluoro- 4-prop-2-ynyl-l ,4-benzoxazin-3-one; and

treating 6-amino-7-fluoro-4-prop-2-ynyl-l,4-benzoxazin-3-one with acetic acid and 3,4,5,6-tetrahydrophthalic anhydride to obtain 2-[7-fluoro-3,4- dihydro-3-oxo-4-(2-propynyl)-2H-l,4-benzoxazin-6-yl]-4,5,6,7-tetrahydro- lH-isoindole-l,3(2H)-dione.