MXPA00000018A - Method for producing 2-(3-pyrazolyl-oxymethylene) nitrobenzenes - Google Patents

Abstract

The invention relates to a method for producing 2-(3-pyrazolyl-oxymethylene) nitrobenzene derivatives of formula (I), wherein the substituents and indices have the meaning given in the Description, by bromination of an o-nitrotoluene of formula (II) and subsequent reaction with a 3-hydroxypyrazol of formula (IV).

Description

PREPARATION OF 2- (3-PIRAZOLYLOXYXIMETHYLEN) ITROBENZENES (sic) The present invention relates to a process for the preparation of 2- (3-pyrazolyl oxoxymethylene) nitrobenzene [sic] derivatives of the formula I where R1 is halogen; t alkyl or unsubstituted or substituted alkoxy; R is cyano, halogen, alkyl, haloalkyl, alkoxy, alkylthio or alkoxycarbonyl; R is alkyl, alkenyl < alkynyl, unsubstituted or substituted; unsubstituted or substituted, saturated or monounsaturated or diunsaturated carbocyclyl; unsubstituted or substituted aryl or heteroaryl; is 0, 1 or 2, it being possible for the substituents R 2 to be different when m is greater than 1; n is 0, 1, 2, 3 or 4, it being possible for the substituents R1 to be different when n is greater than 1; by bromination of an o-nitrotoluene of formula II wherein R1 has the above-mentioned meaning, to provide the o-nitrobenzyl bromide of formula III in the presence of a non-polar aprotic solvent and by the subsequent reaction of the resulting solution of III with a 3-hydroxypyrazole of formula IV where R2 and R3 have the meanings mentioned above, in the presence of a base. Numerous processes for the preparation of o-nitrobenzyl bromide of the formula III starting from o-nitrotoluene II derivatives are described in the literature. In many cases, due to the deactivation by the nitro group, the side chain bromination is carried out only at temperatures above 100 ° C and under pressure. These conditions are disadvantageous taking into account the low thermal stability of the o-nitrobenzyl bromides and are problematic in terms of industrial safety (see Z. Chem. 12 (1972) 139). WO 96/01256 describes the preparation of derivatives I of 2- (3-pyrazolyloxymethylene) nitrobenzene [sic] starting from bromides of o-nitrobenzyl III in general. No details of the industrial preparation of III are given in this publication. Nor does the publication provide any assistance with regard to the management of III in the implementation of the procedure described on an industrial scale. The handling of industrial quantities of III is problematic due to the lachrymatory effect and irritation of the mucosa of III and due to the thermal instability of III that was already mentioned. It is an object of the present invention to find a route to derivatives I of 2- (3-pyrazolyl oxoxymethylene) itrobenzene [sic] which is industrially applicable and, on the other hand, solves the difficult operation and safety issues regarding the handling of III and , on the other hand, offers the required product I with good performance and good purity. Compounds of formula I are important intermediates for the preparation, among other things, of the fungicidal agents described in WO 96/01256.

We have found that this object is achieved through the procedure mentioned at the beginning, where the solution of o-nitrobenzyl bromide III resulting from bromination also reacts with IV, in the solvent used, directly without intermediate isolation of o-nitrobenzyl bromide III. Surprisingly, the novel process offers the required compound I in good yield with excellent purity. This was not expected since the bromination is always carried out with the formation of considerable amounts of o-nitrobenzal bromide V, which can react with 3, -hydroxypyrazoles IV to give bis-O-alkylated acids of the formula VI.

IV VI LV formation can be virtually completely suppressed by the use of 3-hydroxypyrazole IV, which is the most expensive component, in equimolar amounts, or even less, in relation to o-nitrobenzyl III bromide. The selectivity of the alkylation reaction is surprising; On the contrary, the substrates of o-nitrobenzyl bromide III and o-nitrobenzal bromide V can be considered as having a comparable reactivity. The novel process can be employed to prepare 2- (3-pyrazolyloxymethylene) nitrobenzene [sic] derivatives of the formula I. The meanings specified above for the substituents R1 to R3 in the formula I represent collective terms for individual lists of unique members of the groups. All alkyl portions can be straight or branched chain. Halogenated substituents preferably have 1 to 6 identical or different halogen atoms. Examples of specific meanings are: halogen: fluorine, chlorine, bromine and iodine; the alkyl or the alkyl portions of alkoxy, alkoxycarbonyl and alkylthio: straight or branched chain saturated hydrocarbon radicals, particularly those having from 1 to 10 carbon atoms, for example Ci-Cß alkyl, such as 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 -dimetilpropilo, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1, 1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2, 2-dimetilbutils, 2 , 3-dimethylbutyl, 3,3- dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1, 2, 2-trimethylpropyl, 1-ethyl-l-methylpropyl and l-ethyl-2-methylpropyl; alkenyl: unsaturated, straight chain or branched hydrocarbon radicals, particularly those having from 2 to 10 carbon atoms and a double bond at any position, for example C2-Ce alkenyl such as for example ethenyl, 1-propenyl, 2-propenyl , 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, -pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl -2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1, 2 -dimethyl-l-propenyl, 1, 2-dimethyl-2-propenyl, 1-ethyl-l-propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5 -hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl , 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-m ethyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, l-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl- 4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-1-butenyl, 1,2-dimethyl-2-butenyl, 1, 2-dimethyl- 3-butenyl, 1,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl- l-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3, 3-dimethyl-l-butenyl, 3, 3-dimethyl-2-butenyl, 1-ethyl-l- butenyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, 2-ethyl-l-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1, 1, 2-trimethyl- 2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl; alkynyl: straight or branched chain hydrocarbon groups, in particular those having from 2 to 20 carbon atoms and a triple bond at any position, for example C2-C3 alkynyl such as, for example, ethynyl, 1-propynyl, 2-propynyl, 1-Butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-2-butynyl, 1-methyl-3 butynyl, 2-methyl-3-butynyl, 3-methyl-1-butynyl, 1, 1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4- Hexylin, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl- l-pentynyl, 3-methyl-4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1, 1-dimethyl-2-butynyl, 1, 1-dimethyl-3-butynyl, 1, 2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, l-ethyl-2-butynyl, l-ethyl-3-butynyl, 2-ethyl-3- butynyl and l-ethyl-1-methyl-2-propynyl; haloalkyl: straight or branched chain alkyl groups having from 1 to 4 carbon atoms (in accordance with the above), it being possible for the hydrogen atoms in these groups to be partially or totally replaced by halogen atoms in accordance with specified above, for example C1-C2 haloalkyl, such as chloromethyl, dichloromethyl, trichloromethyl, fluoro ethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2,2 , 2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl and pentafluoroethyl; carbocyclyl or heterocyclyl saturated or ounsaturated or diunsaturated: for example carbocycles such as cyclopropyl, cyclopentyl, cyclohexyl, 2-cyclopentenyl, 2-cyclohexenyl or heterocyclyl such as 2-tetrahydrofuranyl, 2-tetrahydrothienyl, 2-pyrrolidinyl, 3-isoxazolidinyl, 3- isothiazolidinyl, 1,3-4-oxazolidin-2-yl, 2,3-dihydro-2-thienyl, 4,5-isoxazolin-3-yl, 3-piperidinyl, 1,3-dioxan-5-yl, 4- piperidinyl, 2-tetrahydropyranyl, 4-tetrahydropyranyl; aryl or hetaryl: for example, phenyl or naphthyl, preferably phenyl or 1- or 2-naphthyl, and hetaryl radicals, for example, 5-membered heteroaromatic rings containing from 1 to 3 nitrogen atoms and / or an oxygen atom or sulfur such as, for example, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, isothiazolyl, 5-isothiazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazyl, 1-imidazolyl , 2-imidazolyl, 4-imidazolyl, 1, 2, 4-oxadiazol-3-yl, 1, 2, 4-oxadiazol-5-yl, 1, 2,4-thiadiazol-3-yl, 1,2,4 -thiadiazol-5-yl, 1, 2, 5-triazol-3-yl, 1, 2, 3-triazol-4-yl, 1, 2, 3-triazol-5-yl, 1, 2, 3-triazole 4-yl, 5-tetrazolyl, 1,2,3,4-thiatriazol-5-yl and 1, 2, 3, 4-oxatriazol-5-yl, particularly 3-isoxazolyl, 5-isoxazolyl, 4-oxazolyl, 4-thiazolyl, 1,3,4-oxadiazol-2-yl and 1,3,4-thiadiazol-2-yl; "unsubstituted or substituted" with reference to alkyl, alkenyl and alkynyl groups and with reference to aryl and hetaryl is intended to express the fact that these groups may be partially or fully halogenated (ie, the hydrogen atoms in these groups may be partially or completely replaced by identical or different halogen atoms as mentioned above (preferably fluorine, chlorine and bromine, in particular fluorine and chlorine)) and / or can carry one to three, particularly one, of the following radicals: alkoxy Ci -Cβ, haloalkoxy C? -C6, alkylthio Ci-Ce, haloalkylthio Ci-C?, Alkylamino C? -C6, dialkylamino C? -C6, alkenyloxy C2-C6, haloalkenyloxy C2-Cd, alkynyloxy C2-C?, Haloalkynyloxy C2-C6 , C3-C6 cycloalkyl, C3-C6 cycloalkoxy, C3-C6 cycloalkenyl, C3-C6 cycloalkenyloxy, C? -C5 alkylcarbonyl, C? -C6 alkoxycarbonyl, C? -C6 alkylaminocarbonyl, C? -C6 dialkyloxycarbonyl, C? -C6 alkylcarbonyloxy? C6, alkylcarbonylamino Ci-Cß-Aryl and h Etaryl can carry, in addition to the aforementioned, one to three of the following radicals: C?-C6 alkyl and C?-C6 haloalkyl. Suitable solvents for the novel process are solvents that are inert during bromination and subsequent alkylation, for example, aromatic hydrocarbons such as benzene, tert-butylbenzene, tert-amylbenzene, or halogenated hydrocarbons, such as, for example, methylene chloride 1 , 2-dichloroethane, chloroform, tetrachloromethane, orthodichlorobenzene or para-dichlorobenzene, 1, 2, 4-trichlorobenzene and, particularly chlorobenzene. The ortho-nitrotoluenes II used in the novel process can, in most cases, be purchased or can be obtained in a simple manner by known methods (for example Organikum Barth Verlagsgesellchaft (1993) 320 et seq.). Bromination agents which can be used to brominate ortho-nitrotoluenes II are elemental bromine or bromine salts, such as, for example, sodium bromide, and hydrogen bromide, preferably in the form of hydrobromic acid, the latter two being used preferably in the presence of an oxidation agent. A technical azeotropic mixture of hydrobromic acid (about 47%) is particularly preferred. Examples of suitable oxidizing agents for oxidizing hydrogen bromide and bromide ions are peracids, peroxides, chlorine bleach solutions, sodium bromate and potassium peroxodisulfate, and hydrogen peroxide is particularly suitable. In a preferred embodiment of the novel process, the amounts of oxidation agents that are employed are such that the hydrogen bromide formed in the reaction is also reoxidized. Preferably, from 1.5 to 2.0 equivalents of the oxidizing agent are added per bromide equivalent. On the other hand, if elemental bromine is used as a source of bromine, it is also possible to avoid the use of an oxidizing agent or, if it is desired to oxidize the hydrogen bromide formed in the reaction, it is sufficient to add from 0.5 to 1.0 equivalent (based on bromine) of an oxidizing agent. It is possible in this way to almost halve the amount of bromination agent used. The brominating agent is generally used in a molar ratio of 0.7 to 1.3, and preferably in a molar ratio of 0.9 to 1.0, relative to o-nitrotoluene II.

Preferred initiators for generating the bromine free radicals that are required for the reaction in the novel process are azo compounds such as, for example, azocarboxylic esters and azocarbonitriles. Azoisobutyronitrile is particularly preferably used. The initiators are generally added in a concentration of 0.1 to 20 mol%, based on o-nitrotoluene [sic] (II), and preferably at a concentration of 1 to 10 mol%, relative to the reaction mixture. . The bromination is carried out at a temperature of 20 to 100 ° C, preferably 20 to 80 ° C. The optimum reaction temperature depends in the first instance on the thermal stability of the o-nitrotoluene II and the product III obtained there, and second on the decomposition temperature of the initiator. The following table summarizes the various initiators with their decomposition structures and temperatures with a half-life of 10 h. The reaction is preferably carried out slightly above or below the half-life decomposition temperature of 10 h of the initiator (± 10 ° C). Designation A Name 2,2 '-azobis (4-methoxy-2,4-dimethylvaleronitrile) Structure OCH 3 CH 3 CH 3 OCH 3 CH3 C CH2 - C N = N C CB2 C CH3 CH3 CN CN CH3 * c Decomposition temperature of half-life of 10 h ° C Designation B Name 2,2'-azobis (2-cyclopropylpropionitrile) Structure Decomposition temperature of. average life of 10 h 42 ° C Designation C Name 2, 2'-azobis (2,4-dimethylvaleronitrile) Structure CH3 CH3 CH3 CH CH2 C N = N C CH2 CH CH3 CH3 CN CN CH3 Decomposition temperature of half-life of 10 h 51 ° C Designation D Name 2, 2 '-azobis (2-methylpropionitrile) Structure Decomposition temperature of half-life of 10 h 65 ° C Designation E Name Dimethyl-2 '2' -azobis (2-methylpropionate) Structure CH3 CH3 I I CH3 C N = N C CH3 COOCH3 COOCH3 Decomposition temperature of half-life of 10 h 66 ° C Designation F s i Name 2, 2 '-azobis (2-methylbutyronitrile) Structure Decomposition temperature of half-life of 10 h 67 ° C Designation G Name 1, 1 '-azobis (cyclohexane-1-carbonitrile) Structure Decomposition temperature of half-life of 10 h 88 ° C Bromination is preferably carried out in a two-phase system. The two-phase system generally comprises the solution of the bromine salt in water or preferably the hydrobromic acid together with the solvent employed and, if appropriate, the initiator or a partial amount of the initiator. The mixture is brought to the temperature of the reaction and then the nitrotoluene II is introduced in the presence or absence of the initiator, continuously or in portions over the course of a half hour to several hours. The measured introduction of II is generally carried out in parallel with the measured introduction of the oxidizing agent in such a way that no excess bromine is present in the reaction mixture. In the same way it is possible to mix the substrate II with the bromination agent and the initiator and to control the reaction by the measured introduction of the oxidizing agent. When bromine is used as a bromine source, the procedure is generally similar to that described, but bromine is introduced in a measured manner into a mixture of water and solvent, with or without initiator. With this method, the substrate II can be present from the beginning or be added in a measured manner. If stable oxidizing agents are employed, they may be mixed with the substrate II, and the course of the reaction may be controlled by the addition of the bromine component. The bromination can be carried out in batches and, preferably, continuously. The continuous process has the advantage that the dimensions of the apparatus are smaller and consequently smaller amounts of solutions containing the substrate II are maintained at an elevated temperature. h Since II is extremely thermally unstable, the continuous process therefore has an advantage in terms of industrial safety. When the introduction is complete, the reaction mixture is usually maintained at the chosen reaction temperature for 0.5 to 3 hours. The organic phase is then separated and used without further purification or drying, in the alkylation step. The solvent used in the alkylation step is the same as in the bromination step. It is possible to add a polar solvent for this stage. The 3-hydroxypyrazoles IV are known in the literature or can be prepared by methods described herein (for example Chem. Phar. Bull. 19 (1971) 1389-1394). The compounds IV are obtained in a particularly advantageous manner by the processes described in WO 97/03939, EP-A 680 945 and DE App. No. 19 652 516.0. The 3-hydroxypyrazoles that are formed can, in some cases, be subjected to subsequent alkylation directly as aqueous solutions. The alkylation of IV with the o-nitrobenzyl bromides III is generally carried out at a temperature between 20 and 90 ° C and preferably from 40 to 80 ° C. O-nitrobenzyl bromide III is generally used in a molar ratio of 0.9 to 1.3, preferably in a molar ratio of 1.0 to 1.2, relative to IV. Bases which are generally suitable are inorganic compounds such as for example alkali metal hydroxides or alkaline earth metal hydroxides (for example lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide), alkali metal oxides and metal oxide alkaline earth (for example lithium oxide, sodium oxide, calcipium oxide, and magnesium oxide), alkali metal hydrides and alkaline earth metal hydrides (eg, lithium hydride, sodium hydride, potassium hydride, and calcium hydride), alkali metal amides (for example lithium amide, sodium amide and potassium amide), alkali metal carbonates and alkali metal carbonates (for example, lithium carbonate and calcium carbonate) and bicarbonates of alkali metal (for example sodium bicarbonate), organometallic compounds, particularly alkali metal alkyls (for example, methyllithium, butyllithium and phenyllithium), alkylmagnesium halides (for example methylmagnesium chloride) as well as alkali metal alcoholates and earth metal alcoholates (for example, sodium methanolate, sodium ethanolate, potassium ethanolate, potassium tert-butanolate and dimethoxymagnesium), as well as organic bases, for example , tertiary amines such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines such as collidine, lutidine and 4-dimethylaminopyridine, as well as bicyclic amines. Sodium hydroxide and potassium hydroxide are particularly preferred. The bases are generally used in equimolar amounts, in excess, or, if appropriate, as solvents. It may be helpful for the reaction to add a catalytic amount of a crown ether (eg, 18-cro n-6 or 15-cro n-5). The reaction can also be carried out in two-phase systems consisting of a solution of hydroxides or carbonates of alkali metal or alkaline earth metal in water and of an organic phase (for example, aromatic and / or halogenated hydrocarbons). Suitable phase transfer catalysts in this case are, for example, ammonium halides and tetrafluoroborates (for example, benzyltriethylammonium chloride, benzyltributylammonium bromide, tetrabutylammonium chloride, hexadecyltrimethylammonium bromide or tetrabutylammonium tetrafluoroborate) and phosphonium halides (eg example, tetrabutylphosphonium chloride and tetraphenylphosphonium bromide). Particular preference is given to tetrabutylammonium bromide, hydroxide and disulfate. It may be beneficial for the reaction to initially convert the 3-hydroxypyrazole with the base to the corresponding hydroxylate, which then reacts with the benzyl derivative. The alkylation step can also be carried out in batches or continuously. Procedure examples The novel procedure will be explained in detail, taking the example of the synthesis of 2- [(Mp-chlorophenyl) -3-pyrazolyloxy-methyl] nitrobenzene [sic] la by a) bromination of ortho-nitrotoluene and b) reaction of ortho-nitrobenzyl bromide Illa resulting with 3-hydroxy-N- (p-chlorophenyl) pyrazole IVa. Example 1 a) Preparation of o-nitrobenzyl bromide A solution of 6.6 g (1 mol% based on hydrobromic acid) of azoisobutyronitrile (AIBN) in 1350 g of chlorobenzene was mixed with 620 g (3.6 mol) of bromhydric acid ala 47% in a flat-bottomed 2.5-liter bottle with a paddle agitator (300 rpm) and diverter. The content of the reactor was heated to a temperature of 75 ° C. After reaching this temperature, feeds I and II were fed through two metering pumps. Feed I: a solution of 26.2 g (4 mol%) of AIBN in 548 g (4.0 mol) of ortho-nitrotoluene was introduced continuously for 2 hours; Feed II: 725 g (3.2 mol) of H202 were introduced into the % in such a way that no excess of bromine was present in the solution. Approximately 2. 5 hours for this. After finishing the feed, the stirring was continued at a temperature of 75 ° C for 2 hours, and then the stirrer was turned off and the phases were separated at a temperature of 75 ° C. 2146.4 g of organic phase were obtained with the following composition (in accordance with quantification by HPLC): 23.6% of o-nitrobenzyl bromide 8.4% of o-nitrotoluene 7.1% of o-nitrobenzal bromide Performance of o-nitrobenzyl bromide: 58.1% based on o-nitrotoluene b) Preparation of 2- [(Mp-chlorophenyl) -3-pyrazolyl-oxymethyl] nitrobenzene [sic] 101.5 g (0.5 mol) of 3-hydroxy-N- (p-chloro) were mixed phenyl) pyrazole 95.8%, 875 g of 5% aqueous KOH and 40.25 g (0.025 mol) of a solution of 20% aqueous tetrabutylammonium bromide in a flat-bottomed 2.5-liter flask with a paddle stirrer (420 rpm) and derailleur. This mixture was homogeneous after being heated to 80 ° C, and 504 g of the organic phase obtained in step a) (equivalent to 0.55 mol of o-nitrobenzyl bromide) was introduced in the course of 5 minutes. The mixture was then stirred at a temperature of 80 ° C for 1 hour and subsequently the contents of the vessel were cooled to a temperature below 10 ° C, reducing the agitator speed to 200 rpm. The residue was filtered, boiled twice in methanol and filtered again, and finally dried under a pressure of 100 mbar. Yield: 141 g (85.6%) of the required product with a melting point of 147 ° C. The following examples show variants of the process of step a): the solution of o-nitrobenzyl bromide in chlorobenzene obtained in each case can be used, as indicated in Example 1, directly in the alkylation step b). Example 2 Use of 2,2'-azobis (2,4-dimethylvaleronitrile) as an initiator 13.7 g (0.1 mol) of o-nitrotoluene, 25 g of chlorobenzene, 600 mg (2.7 mmol) of V 65 (supplied by Wako) were mixed. 2, 2'-azobis (2, -dimethylvaleronitrile)), 300 mg of H2SO4 and 16.4 g (0.15 mol) of 30% hydrogen peroxide at a temperature of 45 ° C. 10 g of 47% hydrobromic acid were added dropwise in 75 minutes, and the mixture was stirred at a temperature of 45 ° C for an additional 75 minutes. An additional 5 g of hydrobromic acid was added, and the mixture was stirred at room temperature for 12 hours. Then 3 g of hydrobromic acid were added, and in two portions, 15.86 g of a solution of chlorobenzene and V 65 (total of 15 g of chlorobenzene + 0.86 g (3.9 mmol) of V 65). A qualitative HPLC [sic] of the organic phase after the end of the reaction showed the following composition (data in percentage area): 52.6% o-nitrobenzyl bromide 35.5% o-nitrotoluene 4.3% o-nitrobenzal bromide 6.5 Chlorobenzene% Example 3 Bromine as bromination agent A mixture of 122.7 g of chlorobenzene, 45.5 g of water and 0.6 g (1 mol%) of AIBN was heated at a temperature of 75 ° C. After reaching this temperature, a solution of AIBN in 49.8 g (0.36 mol) of o-nitrotoluene was added dropwise over the course of 1 hour and, in parallel, a total of 44.1 g (0.28 mol) of bromine of such so that the solution of the reaction remained permanently discolored (pale yellow / pale orange color). Stirring was carried out at a temperature of 75 ° C for 1 hour after the completion of the addition. The organic phase was separated at a temperature of 75 ° C. 174.5 g of the organic phase with the following composition: . 1% o-nitrobenzyl bromide 11.3% o-nitrotoluene 3.1% o-nitrobenzal bromide O-nitrobenzyl bromide yield: 50.7% based on o-nitrotoluene. Example 4 Bromination of o-nitrotoluene in a continuous process Feeding per hour: Feeding I: 54.8 g (0.4 mole) of o-nitrotoluene 3.3 g (5 mole%) of AIBN (alpha, alpha'-azoisobutyronitrile) 135 g of chlorobenzene Feeding II: 81.6 g (0.36 mol) of a 15% hydrogen peroxide solution. Feeding III: 62 g (0.36 mol) of hydrobromic acid at 47%. Feeds I to III were fed, by means of feeding pumps to control weight, in parallel (immersed) in the first reactor, at an internal temperature of 75 ° C and at 300 rpm, from a cascade consisting of 3 stirred vessels (capacity of approximately 300 ml) that were connected to each other by free spill. The two phases were separated, in the same continuous manner, in a downstream settler stage at a temperature of 75 ° C. The operation of the system during 18 hours resulted in the following: 3752.2 g of an organic phase with the following composition: 21.5% of o-nitrobenzyl bromide 8.9% of o-nitrotoluene 4.9% of o-nitrobenzal bromide Yield of bromide of o -nitrobenzyl: 51.9% based on o-nitrotoluene. Example 5: more dilute process A mixture of 1500 g of chlorobenzene, 3.3 g (1 mol%) of AIBN and 310.2 g (1.8 mol) of 47% hydrobromic acid was heated to a temperature of 75 ° C. After reaching the temperature, a solution of 13.1 g (4 mol%) of AIBN was added in 274 g (2 mol) of o-nitrotoluene dropwise over the course of 2 hours, and in parallel a total of 408 g ( 1.8 mol) of 15% hydrogen peroxide in such a manner that the reaction solution remained permanently discolored (pale yellow / pale orange color). Stirring was continued at a temperature of 75 ° C for 1 hour after the addition was complete. The organic phase was separated at a temperature of 75 ° C. The remaining 1916.2 g of organic phase had the following composition: 14.2% o-nitrobenzyl bromide% < 4.0% o-nitrotoluene 2.4% o-nitrobenzal bromide O-nitrobenzyl bromide yield: 63% based on o -nitrotoluene Comparative examples 1. Reaction of o-nitrobenzal bromide with 3-hydroxy-N- ( p-chlorophenyl) pyrazole IVa Va Tetra-n-butylammonium bromide was added to a mixture of 6.8 g of N- (p-chlorophenyl) -3-hydroxypyrazole in 53.7 g of a 5% potassium hydroxide solution. A solution of 5 g of o-nitrobenzal bromide in 20 g of chlorobenzene was added, and the mixture was heated to a temperature of 80 ° C [lacuna] after stirring for 90 minutes, the mixture was cooled to 5 ° C and the precipitated solid was removed by suction filtration. It was washed with cold MeOH and then dried at a temperature of 50 ° C under reduced pressure. This resulted in obtaining 6 g of the bispyrazolyl compound Via in the form of a brown solid. An additional 2 g of residue was isolated from the mother liquor and, according to gas chromatography, comprised j 80% of Via. 2. Reaction of o-nitrobenzal bromide and o-nitrobenzyl bromide with 3-hydroxy-N - (p-chlorophenyl) -pyrazole 0. 8 g of tetra-n-butylammonium bromide was added to a solution of 9.9 g (51 mmol) of 97.2% of N- (p-chlorophenyl) -3-hydroxypyrazole 97.2% in 69.6 g of 5% KOH and heated at 80 ° C. At this temperature, a solution of 10.7 g (49.5 mmol) of o-nitrobenzyl bromide and 12.9 g (43.8 mmol) of o-nitrobenzal bromide was added, and the mixture was kept at this temperature for 90 minutes. An HPLC of the reaction mixture showed that the o-nitrobenzyl bromide and the hydroxypyrazole had reacted to provide the required benzyl ether, while the o-nitrobenzal bromide still remained unchanged even at the end of the reaction. The yield of the isolate after cooling, filtration with suction and washing with methanol in this experiment was 72.3%. From Comparison Example 1, it could have been expected that the reactivity of o-nitrobenzal bromide would be similar to the reactivity of o-nitrobenzyl bromide. However, surprisingly, the alkylation is carried out with a high selectivity, as shown in Comparison Example 2.

Claims (2)

CLAIMS 1. A process for preparing 2- (3-pyrazolyloxymethylene) nitrobenzene [sic] derivatives of the formula
1. I where R1 is halogen; alkyl or unsubstituted or substituted alkoxy; R 2 is cyano, halogen, alkyl, haloalkyl, alkoxy, alkylthio or alkoxycarbonyl; R3 is alkyl, alkenyl or alkynyl, unsubstituted or substituted; carbocyclyl or heterocyclyl, unsubstituted or substituted, saturated or monounsaturated or diunsaturated; unsubstituted or substituted aryl or heteroaryl; m is 0, 1 or 2, it being possible for the substituents R 2 to be different when m is greater than 1; n is 0, 1, 2, 3 or 4, it being possible for the substituents R1 to be different when n is greater than 1; by bromination of an o-nitrotoluene of the formula II * wherein R1 has the aforementioned meaning, to provide the o-nitrobenzyl bromide of the formula III in the presence of non-polar aprotic solvent and by subsequent reaction of the resulting solution of III with a 3-hydroxypyrazole of formula IV where R2 and R3 have the meanings mentioned above, in the presence of a base, where the solution of o-nitrobenzyl bromide III resulting from the bromination further reacts with IV, in the solvent employed, directly without intermediate isolation of the bromide of o- Nitrobenzyl III. 2. A process according to claim 1, wherein the molar ratio between the o-nitrobenzyl bromide III and the 3-hydroxypyrazole IV used is 1 -1.
2. 2. A process according to claim 1, wherein the bromination to provide the o-nitrobenzyl bromide III is carried out continuously. A procedure in accordance with the claim 1, wherein both the bromination to provide o-nitrobenzyl bromide III and the subsequent alkylation to provide the 2- (3-pyrazolyl oxymethylene) nitrobenzene [sic] I are carried out continuously. A procedure in accordance with the claim 1, wherein the bromination to provide the o-nitrobenzyl bromide III is carried out in the presence of an azocarbonitrile or azocarboxylic ester as an initiator. A procedure in accordance with the claim 5, wherein the bromination to provide the o-nitrobenzyl bromide III is carried out with hydrobromic acid, with inorganic bromides dissolved in water, or with elemental bromine in the presence of an oxidizing agent. A procedure in accordance with the claim 6, where hydrogen peroxide is used as an oxidizing agent. A process according to any of claims 1 to 7, wherein the bromination and the alkylation are carried out in a two-phase system consisting of an aqueous phase and an organic phase.