PROCESS FOR PREPARING ANTHRANILIC DIAMIDES AND INTERMEDIATES THEREOF.

Abstract

The present invention relates to a novel process for preparing a compound of formula I (see Formula), wherein R1, R2, R3a, R3b, R3c, R4, R5, R6, R7, and Z are as defined in the description. The process comprises a novel and inventive step of converting a dione of formula II into an isatoic anhydride of formula V in a single step (see Formulas), wherein R2 is F, Cl, Br, or I; and R1, R3a, R3b, R3c, R4, R5, R6, R7, and Z are as defined in the description.

Description

PROCESS FOR PREPARING ANTHRANILIC DIAMIDES AND THEIR INTERMEDIATES FIELD OF INVENTION: The present invention relates to a novel process for preparing anthranilic diamides involving the conversion of isatins into isatoic anhydrides. The present invention also relates to a novel process for preparing isatoic anhydrides useful in the preparation of anthranilic diamides. BACKGROUND OF THE INVENTION: Documents WO2003015518, WO2003015519, WO2004067528, WO2005077934 and WO20100069502 disclose the use of anthranilic diamides to control invertebrate pests, such as arthropods. Several patent documents, for example, documents WO2004011447, WO2004111030, WO2006062978, WO2008010897 and WO2012103436, disclose processes for preparing anthranilic diamides and suitable intermediates. However, the processes described in the aforementioned references are laborious or lack sufficient selectivity, and there remains a need to find a simple, efficient, and economical industrial process for the preparation of anthranilic diamides. OBJECT AND SUMMARY OF THE INVENTION: The objective of the present invention is to provide a process suitable for industrialization and convenient for the preparation of anthranilic diamides of formula I. Surprisingly, the present invention provides a solution to this objective by providing a new process that allows the preparation of anthranilic diamides, overcoming at least one of the drawbacks of the process described in the prior art. This objective was achieved, according to the present invention, by providing a new process for preparing a compound of formula I, bZRRnn / Lznz / E / γΐΛΐ § > tu And where, R1es CH3, Bro Cl; R2 is F, Cl, Br, I or CN; R3ay R3bsonindependientes H, C1-C4 alkyl or Cs-Ce-C1-C4 cycloalkyl; R3ces H or C1-C4 alkyl; cf3n=\ V R4is Cl, Br, CF3, OCF2H, OCH2CF3,o R5s F, Cl or Br; R6 is H, F or Cl; Z is CR7o N; and R7es H, F, Cl or Br. The process according to the present invention comprises the step of obtaining a dione of formula II from an aniline II and doral IV hydrate and converting the dione of formula II into an isatoic anhydride of formula V in a single step. The conversion of the dione of formula II into an isatoic anhydride of formula IV is novel and inventive, since both the oxidation and halogenation reactions are carried out in a single step. where R2 is F, Cl, Br or I; R1 and R3 are as previously defined in this document. Isophosphate anhydride of formula V and an amine of formula VI are reacted to obtain a compound of formula VII, which is subsequently reacted with a compound of formula VIII, finally obtaining the compound of formula I, bZRRnn / Lznz / E / YiAi where R1, R2, R3a, R3b, R3c, R4, R5, R6 and Z are as defined for formula I; and R8 is OH, Cl, X or C1-C4 O-alkyl. DETAILED DESCRIPTION OF THE INVENTION: GENERAL DEFINITIONS The definitions provided herein for the terminology used in this disclosure are for illustrative purposes only and are in no way intended to limit the scope of the invention disclosed herein. As used herein, the terms and expressions comprising, comprising, including, having, containing, characterized by, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitations explicitly stated. For example, a composition, mixture, process, or method comprising a list of elements is not necessarily limited to those elements but may include other elements not expressly listed or inherent in that composition, mixture, process, or method. The transitional expression "consists of" excludes any unspecified element, step, or ingredient. If it appears in a claim, it restricts the inclusion in the claim of materials other than those mentioned, except for impurities commonly associated with them. When the expression "consists of" appears in a clause of the body of a claim, instead of immediately following the preamble, it limits only the element set forth in that clause; it does not exclude other elements of the claim as a whole. The transitional expression "essentially consisting of" is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those explicitly disclosed, provided that such additional materials, steps, features, components, or elements do not materially affect the basic and novel features of the claimed invention. The expression "essentially consisting of" occupies a middle ground between "comprising" and "consisting of." Furthermore, unless expressly stated otherwise, "or" refers to an inclusive "or" and not an exclusive "or." For example, a condition A or B is met if any of the following are true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). Furthermore, the indefinite articles *un* and *una*, when preceding an element or component of the present invention, are not intended to be restrictive as to the number of instances (i.e., occurrences) of the element or component. Therefore, *un* and *una* should be read to include *uno* or *una*, and the singular form of the word for the element or component also includes the plural, unless the number is obviously singular. A carbon-based radical refers to a monovalent molecular component comprising a carbon atom that connects the radical to the rest of the chemical structure via a single bond. Carbon-based radicals may optionally comprise saturated, unsaturated, and aromatic groups, chains, rings, and ring systems, as well as heteroatoms. Although carbon-based radicals are not restricted as to any particular size limit, in the context of the present invention they typically comprise from 1 to 16 carbon atoms and from 0 to 3 heteroatoms. Of particular note are carbon-based radicals selected from C1-C3 alkyl, C1-C3 haloalkyl, and phenyl groups, optionally substituted with 1-3 substituents selected from C1-C3 alkyl, halogen, and nitro groups. The meaning of several terms used in the description will be explained below. The term alkyl, used either alone or in compound words such as alkylthio or haloalkyl or -N(alkyl) or alkylcarbonylalkyl or alkylsulfonylamino, includes linear or branched C1 to C24 alkyls, preferably C1 to C15 alkyls, more preferably C1 to C10 alkyls, and most preferably C1 to C10 alkyls. Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, and 1-methylpentyl. 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl or the different isomers.If the alkyl group is at the end of a compound substituent, such as in alkylcycloalkyl, the initial part of the compound substituent, for example, the cycloalkyl group, may be mono- or polysubstituted identically or differently and independently by alkyl. The same applies to compound substituents where other radicals are attached at the end, such as alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy, and the like. The term cycloalkyl means a ring-closed alkyl group. Representative examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. This definition also applies to a cycloalkyl group as part of a compound substituent, e.g., cycloalkylalkyl, etc., unless specifically defined elsewhere. The present invention relates to a process for preparing a compound of formula I, bZRRnn / Lznz / E / γΐΛΐ, where, R1es CH3, Bro Cl; R2 is F, Cl, Br, I or CN; R3ay R3bsonindependientes H, C1-C4 alkyl or Cs-Ce-C1-C4 cycloalkyl; R3ces H or C1-C4 alkyl; CF3nX °x R4is Cl, Br, CF3, OCF2H, OCH2CF3, or ^N'N or -S(°)„.2 ; R5s F, Cl or Br; R6 is H, F or Cl; Z is CR7o N; and R7es H, F, Cl or Br. The process of the present invention is described below in this document. Initially, a dione of formula II is obtained by reacting an aniline of formula III and the hydrate of doral IV, bZRRnn / Lznz / Ε / γΐΛΐ where, R1 and R3c are as defined above herein. In one embodiment, the compound of formula III and the doral hydrate of formula IV are reacted in the presence of one or more suitable reagents, including, but not limited to, hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, nitric acid, and sodium sulfate, in one or more solvents at a temperature in the range of 25°C to 100°C, followed by stirring with a mineral acid, including, but not limited to, sulfuric acid, hydrochloric acid, and nitric acid at 0°C to 45°C, yielding the dione of formula II. In another embodiment, the oxime of formula III is formed by reacting the compound of formula III and the doral hydrate of formula IV or a hydroxylamine, in the presence of one or more suitable reagents, including, but not limited to, hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, nitric acid, and sodium sulfate, and one or more solvents at a temperature in the range of 15 °C to 150 °C. bZRRnn / Lznz / Ε / γΐΛΐ where, R1 and R3c are as defined above herein. The solvent useful in this stage includes, but is not limited to, aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane and the like; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and the like; ethers such as diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethylethane and the like; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and the like; ethers, polar aprotic solvents such as A / ,A / -dimethylmethanamide, dimethyl sulfoxide, A / -methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone and the like; and water. The oxime of formula Illa formed is then converted into the compound of formula II using mineral acid, including, but not limited to, sulfuric acid, hydrochloric acid and nitric acid and stirring at a temperature in the range of 0 °C to 150 °C. The dione of formula II obtained is converted into an isatoic anhydride of formula V using a suitable halogenating reagent, one or more suitable oxidizing reagents and one or more suitable solvents, at a temperature in the range of 0 °C to 250 °C, where R2 is F, Cl, Br or I; R1 and R3 are as previously defined in this document. The halogenating reagent useful for converting the dione of formula II to the isatoic anhydride of formula V includes, but is not limited to, HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2Cl2, COCl2, X2, C(=O)(OCI3)2, β-BuOCI, NaOCI, chloramine-T, β-halosuccinamides, POX3, PX3, PXs or metal halides; wherein X is Cl, Br, I or F. Useful oxidizing reagents for converting the dione of formula II to the isatoic anhydride of formula V include, but are not limited to, hydrogen peroxide, t-butyl hydroperoxide, tungsten peroxide, m-chloroperbenzoic acid, benzoyl peroxide, hypohalous acid, ammonium ceric nitrate, ammonium hypoceric nitrate, oxone, periodic acid, hydrogen peroxide and urea adduct, sodium perborate, pyridinium chlorochromate, and dimethyl sulfoxide. The solvent useful for converting the dione of formula II into the isatoic anhydride of formula V includes, but is not limited to, an organic acid selected from the group consisting of formic acid, acetic acid, triflic acid, butyric acid, propionic acid, benzoic acid, m-chlorobenzoic acid, carbonic acid, glycolic acid, and trifluoroacetic acid. Alternatively, solvents useful for converting the dione of formula II to the isatoic anhydride of formula V include, but are not limited to, a mixture of said organic acids with one or more solvents selected from the group comprising aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane and the like; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and the like; ethers such as diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethyloxyethane and the like; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and the like;polar aprotic solvents, such as A / ,A / -dimethylmethanamide, dimethyl sulfoxide, A / -methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone and the like; and water. In one embodiment, the step of converting the dione of formula II into the isatoic anhydride of formula V is carried out by mixing i) a mixture of the bZRRnn / Lznz / E / YiAi halogenating reagent and the oxidizing reagent and i) a mixture of the dione of formula II and the solvent, at a temperature in the range of 10 to 50 °C and then heating to a temperature in the range of 15-150 °C. In another embodiment, the step of converting the dione of formula II into the isatoic of formula V is carried out by mixing i) the halogenating reagent and i) the oxidizing reagent separately in any sequence with iii) a mixture of the dione of formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15-150 °C. In the next stage, isatoic anhydride of formula V and an amine of formula VI are reacted, yielding a compound of formula Vil, bZRRnn / Lznz / E / YiAi where, R2is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are as defined hereinabove. The amine of formula VI can be used in aqueous or gaseous form. For example, when R3 is methyl, methylamine is used to prepare the compound of formula VII, where R3 is methyl; in this case, the methylamine can be used in gaseous form or as a solution in water or one or more solvents. The solvents useful for this reaction are preferably selected from the group comprising aliphatic hydrocarbons, such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons, such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane and the like; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and the like; ethers such as diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethylethane and the like; halogenated hydrocarbons, such as dichloromethane, chloroform, dichloroethane and the like;ethers, polar aprotic solvents such as Λ / ,Λ / dimethylmethanamide, dimethyl sulfoxide, β-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6 tetrahydro-2(1H)-pyrimidine, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone and the like; and water. The conversion of isatoic anhydride of formula V and amine of formula VI may further require the presence of a suitable reagent which includes, but is not limited to, formic acid, acetic acid, triflic acid, benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, gallic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, boronic acids, Amberlyst, aluminum chloride, zinc chloride, boron trifluoroether, zinc oxide, titanium tetrachloride, tin chloride and combinations thereof. The temperature conditions used for the conversion of isatoic anhydride of formula V and amine of formula VI are in the range of 0 °C to 150 °C, depending on the solvent used and the amine reagent employed. In one embodiment, the compound of formula V is isolated. In another embodiment, the compound of formula V is not isolated. In one embodiment, the isatoic anhydride of formula V, wherein R2 is F, Cl, Br, or I, can be converted into a compound of formula V, wherein R2 is CN. The compound of formula Vil, wherein R2 is F, Cl, Br, or I, can be converted into a compound of formula Vil, wherein R2 is F, Cl, Br, or I, by cyanation. The cyanation of the isatoic anhydride of formula V and / or the compound of formula Vil can be carried out by the process disclosed in WO2008010897, WO2008070158, WO2009085816, and WO2009061991. WO2009006061 and WO2008082502. Finally, the compound of formula Vil and a compound of formula VIII are reacted to obtain the compound of formula I, bZRRnn / Lznz / E / γΐΛΐ bZRRnn / Lznz / Ε / γΐΛΐ wherein, R1, R2, R3a, R3b, R3c, R4, R5, R6and Z are as defined hereinabove; R8is OH, Cl or O-C1-C4 alkyl. The compound of formula VIII can be obtained by any of the 5 processes disclosed in documents WO2003015518, WO20030155519, WO2011157664 and WO2013030100. The present invention also relates to a process for preparing a compound of formula Vil, where, R1es CH3, Bro Cl; R2 is F, Cl, Br, I or CN; R3ay and R3bson are independently H, C1-C4 alkyl or Cs-Ce-C1-C4 cycloalkyl; and R3ces independently H or C1-C4 alkyl. The process for preparing the compound with formula Vil is basically the same as described above in this document. The present invention also relates to a process for preparing a compound of formula V, bZRRnn / Lznz / E / YiAi V where, R1es CH3, Bro Cl; R2 is F, Cl, Br, I or CN; and R3ces H or C1-C4 alkyl. The process for preparing the compound of formula V has been described earlier in this document. Any or all of the steps in the process of the present invention may be carried out continuously, semi-continuously, in flow, or discontinuously. In particular, the steps in the process of the present invention are carried out semi-continuously. All or any of the stages of the process can be carried out at a pressure in the range of 0.5 kg / cm2 to 250 kg / cm2. The present inventions will be described below in light of the following non-limiting examples. Example 1: Step A: Preparation of 2-(hydroxyamino)-A / -(o-tolyl)acetamide Hydrochloric acid (73 g, 700 mmol, 35% w / w) was slowly added to a solution of o-toluidine (75 g, 700 mmol) in water (170 mL), followed by the addition of anhydrous sodium sulfate solution (636 g, 4478 mmol) in water (800 mL). The resulting reaction mixture was heated to 55 °C. An aqueous solution of hydroxylamine hydrochloride (73 g, 1050 mmol) in water (280 mL) was then slowly added, followed by the addition of doral hydrate (125 g, 757 mmol) in water (270 mL). The reaction mixture was maintained at 55 °C for 12 h. After the reaction was complete, the reaction mixture was cooled to 20 °C and stirred for 1 h. The solid product was filtered and washed twice with water (100 ml), obtaining 2-(hydroxymino)- / V-(o-tolyl)acetamide (95 g, 531 mmol, yield: 76%). 1H NMR (400 MHz, DMSO-c / 6) δ 12.16 (s, 1H), 9.47 (sa, 1H), 7.66 (s, 1H), 7.45-7.47 (d, J = 7.8 Hz, 1 H), 7.19-7.24 (dd, J = 7.4 Hz and 0.6 Hz, 1 H), 7.14-7.18 (td, J = 7.6 Hz and 1.6 Hz, 1 H), 7.08-7.13 (td, J = 7.4 Hz and 1.3 Hz, 1 H), 2.22 (s, 3H) MS: m / z = 179.05 [M+H]. Step B-1: Preparation of 7-methylindolin-2,3-dione 2-(Hydroxymino)-A / -(o-tolyl)acetamide (92 g, 485 mmol) was added in batches to a sulfuric acid solution (333 g, 3397 mmol) at 0-5 °C. The temperature was allowed to rise slowly to 30 °C, and the reaction mixture was stirred for 12 h. The reaction mixture was then slowly poured into water (1800 ml), and the precipitated solid product was removed by filtration and washed with water (200 ml), yielding 7-methylindolin-2,3-dione (71.5 g, 485 mmol, yield: 91%). 1H NMR (400 MHz, DMSO-cfc) δ 11.08 (s, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1 H), 6.96 (t, J = 7.6 Hz, 1 H), 2.17 (s, 3H) EM: m / z = 162.00 [M+H]. Step B-2: Preparation of 7-methylindolin-2,3-dione 2-(Hydroxyimino)-A / -(o-tolyl)acetamide (10 g, 15.8 mmol) was added in batches to a solution of sulfuric acid (36.2 g, 369 mmol) and 1,2-dichloroethane (50 mL) at 0–5 °C. The temperature was allowed to rise slowly to 30 °C, and the reaction mixture was stirred for 12 h. The reaction mixture was then slowly poured into water (190 mL). The dichloroethane was removed under reduced pressure, and the remaining suspended solid product was removed by filtration and washed with water (20 mL), yielding 7-methylindolin-2,3-dione (8.1 g, 50 mmol, yield: 95%). Step C-1: Preparation of 6-chloro-8-methyl-2 / - / -benzo[d][1,3]oxazin-2,4(1 H)-dione 7-Methylindolin-2,3-dione (50 g, 261 mmol) and acetic acid (421 g) were mixed at 25 °C to form a suspension. Hydrogen peroxide (163 g, 1437 mmol, 30% w / w) was slowly added to this suspension at 25 °C over 15 min with stirring, followed by the addition of concentrated hydrochloric acid (82.0 g, 653 mmol, 29% w / w) at 30–40 °C over 45 min. The reaction mixture was stirred for 3 h at 40 °C. The reaction mass was then heated to 70 °C for 4 h. It was cooled to 25 °C and then slowly poured onto a crushed ice-water mixture (415 g) with stirring at 0–5 °C. The solid obtained by this procedure was filtered, washed with cold water (100 ml) and vacuum dried, yielding the crude compound 6chloro-8-methyl-2 / - / -benzo[d][1,3]oxazin-2,4(1 H)-dione (46 g, 261 mmol, yield: 83%). bZRRnn / Lznz / E / γΐΛΐ Step C-2: Preparation of 6-chloro-8-methyl-2 / 7-benzo[d][1,3]oxazin-2,4(1H)-dione7-Methylindolin-2,3-dione (20 g, 116 mmol) and acetic acid (187 g, 3127 mmol) were mixed at 25 °C to form a suspension. Hydrogen peroxide (batch-1) (18 g, 232 mmol) was added slowly over 5 min at the same temperature, followed by the addition of hydrochloric acid (51.0 g, 406 mmol) over 30 min at 15 °C. The resulting reaction mixture was stirred for 2 h at 25 °C. Hydrogen peroxide (batch-2) (27 g, 348 mmol) was then added slowly over 30 min at 15 °C with stirring. The reaction mixture was heated to 60 °C and stirred for 6 h. Hydrogen peroxide (batch-3) (12 g, 174 mmol) was slowly added again at 20°C with stirring. The reaction mixture was heated to 60°C and stirred for an additional 2 h. The reaction was slowly stopped by pouring it into cooled water (930 g) at 0°C. The resulting mixture was stirred for 1 h at 0°C and filtered, yielding a solid material.The solid was washed with chilled water (40 g) and dried under reduced pressure at 50 °C overnight, yielding 6-chloro-8-methyl-2 / 7-benzo[d][1,3]oxazin-2,4(1 / 7)-dione (15.4 g, 72.8 mmol, yield: 63%). 1H NMR (400 MHz, DMSO-cfe) δ 11.17 (s, 1H), 7.73 (dd, J = 2.4 Hz and 0.5 Hz, 1 H), 7.69 (dd, J = 2.4 Hz and 0.7 Hz, 1H), 2.34 (s, 3H). EM: m / z = 209.90 [MH], Step C-3: Preparation of 6-chloro-8-methyl-2 / 7-benzo[d][1,3]oxazin-2,4(1 / 7)-dione 7-Methylindolin-2,3-dione (50 g, 298 mmol) and acetic acid (483 g, 8047 mmol) were mixed at 5 °C to form a suspension. Hydrogen peroxide (batch-1) (69 g, 894 mmol) was added slowly to this suspension with stirring at 5 °C for 15 min. Hydrochloric acid (batch-1) (56 g, 447 mmol) was then added very slowly with stirring at 5 °C for 160 min. The resulting reaction mass was further stirred for 2.5 h at 10 °C, then heated to 20 °C and stirred for an additional 23 h. Hydrogen peroxide (batch-2) (26 g, 313 mmol) was added at 10°C for 15 min with stirring, and then HCl (batch-2) (18 g, 158 mmol) was added with very slow stirring over a period of 30 min at 10°C. The reaction mixture was stirred at 40°C for 3 h and filtered under reduced pressure. The resulting filter cake was washed three times with water (600 ml) and dried under reduced pressure at 25°C for 16 h.The raw solid was then dried in a reduced pressure oven (760 mm Hg) at 55 °C for 16 h, yielding 6-chloro-8-methyl-2H-benzo[d][1,3]oxazinbZRRnn / Lznz / E / γΐΛΐ. 2,4(1H)-dione (52.70 g, 298 mmol, yield: 84%). Step C-4: Preparation of 6-bromo-8-methyl-2 / - / -benzo[d][1,3]oxazin-2,4(1 / - / )dione: Hydrogen peroxide (27 g, 360 mmol) was added to a suspension of 7-methylindolin-2,3-dione (10 g, 60.0 mmol) and acetic acid (100 g) at 25–30 °C. Hydrobromic acid (11 g, 57.1 mmol) was added at 15–25 °C for 1 h. After stirring for 2 h at 25–30 °C, sulfuric acid (0.3 g, 3.0 mmol) was added, and the reaction mixture was heated to 45–50 °C and stirred for 8 h. The temperature was then slowly increased to 70–75 °C, and the mixture was stirred for an additional 2 h. After the reaction was completed, the reaction mixture was cooled to 25 °C and slowly poured onto a mixture of crushed ice and water (500 g) with constant stirring at 0-5 °C. The resulting solid was filtered, washed with cold water (100 g) and dried under reduced pressure, yielding crude 6-bromo-8-methyl-2 / 7-benzo[d][1,3]oxazin-2,4(1 H)-dione (11.5 g, 45 mmol, yield: 75%). 1HNMR (400 MHz, DMSO-ofe) δ 11.16 (s, 1H), 7.83 (d, J = 2.4 Hz, 1H), 7.78 (d, J = 2.4 Hz, 1H), 2.31 (s, 3H) CLEM: m / z = 254 [M-2H], Step D-1: Preparation of 2-amino-5-chloro-A / ,3-dimethylbenzamide A suspension of 6-chloro-8-methyl-2-benzo[c-[1,3]oxazin-2,4(7-)-dione (17 g, 80 mmol), acetic acid (10 g, 160 mmol), and ethyl acetate (200 mL) was cooled with stirring to 0 °C. Methylamine gas was bubbled through this suspension with stirring at 0 °C for 15 min (pH 9–10). The resulting reaction mixture was heated to 25 °C and stirred for a further 3 h. After the reaction was complete, the reaction mixture was poured into water (200 g) and extracted twice with ethyl acetate (200 g). The combined ethyl acetate layers were dried over anhydrous sodium sulfate, filtered and distilled under reduced pressure, yielding crude 2-amino-5-chloro-A / ,3-dimethylbenzamide (12.0 g, 60.4 mmol, yield: 75%). RMN1H (400 MHz, DMSO-free) δ 8.31 (d, J = 4.2 Hz, 1H), 7.37-7.38 (d, J = 2.4 Hz, 1H), 7.10-7.12 (d, J = 2.4 Hz, 1H, 35), = 4.4 Hz, 3H), 2.08 (s, 3H). EM: m / z = 199.00 [M+H]. Step D-2: Preparation of 2-amino-5-chloro- / V,3-d¡met¡lbenzamide A mixture of 6-chloro-8-methyl-2 / - / -benzo[c / |[1,3]oxazin-2,4(7 / - / )-dione (0.5 g, bZRRnn / Lznz / Ε / γΐΛΐ 2.4 mmol), methylamine hydrochloride (0.32 g, 4.7 mmol), and potassium carbonate (0.33 g, 2.4 mmol) in ethyl alcohol (10 mL) was stirred for 0.5 h at 25 °C, and then heated to 80 °C for 5 h. After the reaction was complete, the reaction mixture was poured into ice water (50 mL). The solid precipitate was removed by filtration and washed with water (5 mL). The mother liquor was extracted twice with dichloromethane (50 mL). The combined dichloromethane layers were dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure, yielding a solid. The two solids were combined, yielding crude 2-amino-5-chloro-A / ,3-dimethylbenzamide (0.3 g, 1.5 mmol, yield: 64%). Step D-3: Preparation of 2-amino-5-chloro-A / ,3-dimethylbenzamide A mixture of 6-chloro-8-methyl-2 / - / -benzo[d][1,3]oxazin-2,4(H)-dione (0.5 g, 2.4 mmol), methylamine hydrochloride (0.32 g, 4.7 mmol), and pyridine (0.4 mL, 4.7 mmol) in ethyl alcohol (10 mL) was heated at 80 °C for 2 h. After the reaction was complete, the reaction mixture was diluted with water (50 mL) and extracted twice with ethyl acetate (50 mL). The combined ethyl acetate layers were dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure, yielding a crude solid. The crude solid was ground with n-hexane (50 ml), yielding pure 2-amino-5-chloro-A / ,3-dimethylbenzamide (0.3 g, 1.4 mmol, yield: 60%).

Claims

1. A process for preparing an anthranilic diamide of formula I, CI, Br, CF3, OCF2H, OCH2CF3, N os<°)o-2; F, CI or Br; H. Fo CI: wherein, R1 is CH3, Bro CI; R2 is F, CI, Bro I; R3a and p3b are independently H, C1-C4 alkyl or Cs-Ce-cycloalkyl C1-C4 alkyl; R3c is H or C1-C4 alkyl; Cp3 N^< °\ _ .. ¿ ,NH R4 is R5 is R6 is Z is CR7 or N; and R7 is H, F, CI or Br, said process comprising the steps of: a) obtaining a dione of formula II by reacting a compound of formula III, doral hydrate of formula IV and hydroxylamine, in the presence of at least one suitable reagent; or III IV II or obtain the dione of formula II by cycling a compound of formula Illa in the presence of at least one suitable reagent; bZRRnn / Lznz / E / γΐΛΐ wherein the compound of formula Illa is obtained as an intermediate in the process step of reacting the compound of formula III, doral hydrate of formula IV and hydroxylamine, in the presence of at least one suitable reagent;III IV II wherein, R1 and R3c are as defined above in this document, b) oxidizing and halogenating the dione of formula II simultaneously into an isatoic anhydride of formula V using at least one oxidizing reagent and at least one halogenating reagent in the presence of at least one suitable acid; wherein, R1, R2 and R3c are as defined above in this document, c) reacting the compound of formula V with an amine of formula VI, obtaining a compound of formula V1 in the presence of at least one suitable reagent; wherein, R1, R2, R3a, R3b and R3c are as defined above in this document, and d) reacting the compound of formula V1 and a compound of formula VIII with the compound of formula I in the presence of at least one reagent bZRRnn / Lznz / E / YiAi wherein, R8 is OH, Cl, X or C1-C4 O-alkyl;R1, R2, R3a, R3b, R3c, R4, R5, R6 and Z are as defined above in this document and where the compound of formula V may or may not be isolated.; 2. The process according to claim 1, wherein step (a) of the process is carried out i) using at least one suitable reagent selected from the group consisting of hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, nitric acid and sodium sulfate; i) at a temperature in the range of 0 °C to 150 °C; and iii) use at least one solvent selected from the group consisting of hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylene, mesitylene, benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, dietoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-midazolidone and water.

3. The process according to claim 1, wherein step (b) of the process is carried out i) using a suitable halogenating reagent selected from the group consisting of HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2Cl2, COCl2, X2, C(=O)(OCl3)2, f-BuOCl, NaOCl, chloramine-T, / V-halosuccinamides, POXs, PX3, PXs or metal halides; wherein X is Cl, Br, I or F, in particular, Cl; i) using at least one suitable oxidizing reagent, hydrogen peroxide, t-butyl hydroperoxide, tungsten peroxide, m-chloroperbenzoic acid, benzoyl peroxide, hypohalous acid, ceric ammonium nitrate, hypoceric ammonium nitrate, oxone, periodic acid, hydrogen peroxide and urea adduct, sodium perborate, pyridinium chlorochromate and dimethyl sulfoxide;iii) using at least one acid selected from the group consisting of formic acid, acetic acid, triflic acid, benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, gallic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid and perchloric acid; iv) at a temperature in the range of 0 °C to 150 °C;(yv) using at least one solvent selected from the group consisting of hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylene, mesitylene, benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, dietoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone and water.; 4. The process according to claim 1, wherein step (b) of the process is carried out by mixing i) a mixture of the halogenating reagent and the oxidizing reagent and i) a mixture of the dione of formula II and the solvent, at a temperature in the range of 10 to 50 °C and then heating to a temperature in the range of 15-150 °C.

5. The process according to claim 1, wherein step (b) of the process is carried out by adding i) the oxidizing reagent and ii) the halogenation reagent separated in any sequence in portions or all at once to iii) a mixture of the dione of formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15-150 °C.

6. The process according to claim 1, wherein step (c) of the process is carried out i) using at least one suitable reagent selected from the group consisting of formic acid, acetic acid, triflic acid, benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, gallic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydriodic acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, boronic acids, Amberlyst, aluminum chloride, zinc chloride, boron trifluoroether, zinc oxide, titanium tetrachloride, tin chloride, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, pyridine, N-methyl-2-pyrrolidone and Ν,Ν-dimethylmetanamide; ¡i) at a temperature in the range of 0 °C to 150 °C;and iii) using at least one solvent selected from the group consisting of formic acid, acetic acid, triflic acid, butyric acid, propionic acid, benzoic acid, m-chlorobenzoic acid, carbonic acid, glycolic acid and trifluoroacetic acid, optionally in combination with at least one additional solvent selected from the group consisting of hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylene, mesitylene, benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, dietoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone and water.

7. The process for preparing the anthranilic diamide of formula I according to claim 1, bZRRnn / Lznz / Ε / γΐΛΐ bZRRnn / Lznz / Ε / γΐΛΐ wherein, R1 is CH3, Br or Cl; R2 is Cl; R3a is H and R3b is methyl or 1-cyclopropyl ethyl; R3c is H; CF3 nX A l ,N R4 is Br, n'n or R5 is Cl; R6 is H or Cl; and Z is N. S(O)0.2 8. A one-step, one-vessel process for preparing a compound of formula V, wherein the process comprises one step of: simultaneously oxidizing and halogenating the dione of formula II into an isatoic anhydride of formula V, using at least one oxidizing reagent and at least one halogenating reagent in the presence of at least one suitable acid; wherein R1 is CH3, Br or Cl; R2 is F, Cl, Bro I; R3a and R3b are independently H, C1-C4 alkyl or Ca-Ce-C1-C4 cycloalkyl; and R3c is independently H or C1-C4 alkyl.

9. The process according to claim 8, wherein i) the halogenating reagent is HCl, SOCl2, NaOCl and Cl2; ii) using at least one suitable oxidizing reagent selected from the group consisting of hydrogen peroxide, m-chloroperbenzoic acid, periodic acid; iii) using at least one acid selected from the group consisting of formic acid, acetic acid, trifluoroacetic acid, benzoic acid, m-chlorobenzoic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, hydroiodic acid, sulfuric acid and periodic acid; iv) at a temperature in the range of 5 °C to 80 °C; (yv) using at least one solvent selected from the group consisting of toluene, xylene, t-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, monoglime, diglyme, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone and water.

10. The process according to claim 8, wherein i) the oxidizing reagent and iii) the halogenating reagent are added separately in the sequence in portions to iii) a mixture of the dione of formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15-150 °C.