Title of Invention	A PROCESS FOR THE PREPARATION OF THIAZOLE DERIVATIVES
Abstract	The process for the preparation of thiazole derivatives of formula (I) and, where appropriate, an E/Z isomer, a mixture of E/Z isomers and/or a tautomer thereof, in each case in free form or in salt form wherein a) a compound of formula (II) is reacted with a chlorinating agent at a temperature of 0˚C to 50˚C using chlorine, POC1<sub>3,</sub> PC1<sub>3,</sub> PC1<sub>5</sub> or SO<sub>2</sub>C1<sub>2</sub> or a mixture of chlorine and SO<sub>2</sub>C1<sub>2</sub> as chlorinating agent to form a compound of formula (III) or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and b) the compound of formula (III) thereby obtained is reacted at a temperature of 10˚C in the presence of a base with a compound of formula (IV) in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of acatalytic amount of SO<sub>2</sub>.

Title of Invention

A PROCESS FOR THE PREPARATION OF THIAZOLE DERIVATIVES

Abstract

The process for the preparation of thiazole derivatives of formula (I) and, where appropriate, an E/Z isomer, a mixture of E/Z isomers and/or a tautomer thereof, in each case in free form or in salt form wherein a) a compound of formula (II) is reacted with a chlorinating agent at a temperature of 0˚C to 50˚C using chlorine, POC13, PC13, PC15 or SO2C12 or a mixture of chlorine and SO2C12 as chlorinating agent to form a compound of formula (III) or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and b) the compound of formula (III) thereby obtained is reacted at a temperature of 10˚C in the presence of a base with a compound of formula (IV) in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of acatalytic amount of SO2.

Full Text	The invention relates to a process for the preparation of thiazole derivatives. (A) to a process for the preparation of a compound of formula and, where appropriate, E/Z isomers, mixtures of E/Z isomers and/or tautomers thereof, in each case in free form or in salt form, wherein Q is CH or N; Y is NO2 or CN Z is CHR3, O, NR3 or S; R1 and R2 either are each independently of the other hydrogen or C1-C8-alkyl which is unsubstituted or substituted by R4 or together are an alkylene bridge having two or three carbon atoms which optionally contains a hetero atom selected from the group consisting of NR5, O and S, R3 is H or C1-C12-alkyl which is unsubstituted or substituted by R4, R4 is unsubstituted or substituted aryl or heteroaryl, and R5 is H or C1C12-alkyl wherein a) a compound of formula which is known or which can be prepared by known methods and wherein X is a leaving group, is reacted with a chlorinating agent to form a compound of formula or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and b) the compound of formula (III) thereby obtained is reacted with a compound of formula which is known or which can be prepared by methods known perse and wherein Ri, R2. Y. Z and Q are as defined hereinbefore for the compound of formula (I); in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of catalytic amounts of SO2; to a process for the preparation of a compound of formula (III) according to process step a) hereinbefore, and to the use of compounds of formulae (II), (III) and (IV) in a process as described hereinbefore. The compounds of formula (I) are known as valuable pesticides, and synthesis rriethods for those compounds are described in the literatuje. It has, however, been found that significant safety problems occur in the case of those processes known from the literature. It has moreover been found that the compound of formula (III) prepared according to the known processes does not satisfy the requirements in terms of purity either, that it isl - probably because of those impurities - thermally unstable, which in turn can lead to significant problems in a production plant, and also that the known processes have significant disadvantages in respect of further parameters, for example yield, duration of the synthesis cycle, volume yield, disposal of ecologically and toxicologically problematic wastes, for example solvents, SO2, and the like. The known preparation processes are therefore not satisfactory in every respect, which is why there is a need to provide improved preparation processes for the compounds of formula (I) and especially of formula (III). In Example 1 of EP-A-446 913, the compound of formula (II) hereinbefore is reacted with chlorine, 2-chloro-5-chloromethyl-thiazole of formula (III) above being obtained in a crude yield of 73 %. In Example 2 of EP-A-446 913, the same reaction is carried out, but using SO2CI2 instead of chlorine. The crude yield in that Example is 82 %. The content of 2-chloro-5-chloromethyl-thiazole is not mentioned in Example 1 of EP-A-446 913. In Example 2, a content of slightly more than 90 % 2-chloro-5-chloromethyl-thiazole is mentioned, from which it is possible to deduce a yield of about 74 % of theory. The increased yield in the case of the process using SO2CI, however, is itself a major advantage for production on a large industrial scale: using the method carried out with SO2CI2, more material can be prepared in the same unit of time than when CI2 is employed, certain waste substances are produced in significantly smaller amounts by that means, and there are further advantages besides. However, the use of SO2CI2 has the significant disadvantage that stoichiometric amounts of SO2 are produced, which have to be removed, either by recycling the SO2 to SO2CI2 using CI2 or by having to convert the SO2 into S042 by oxidation. However, S042 is a waste substance which, although not ecologically harmful, seriously attacks the concrete walls of waste water purification systems and is therefore extremely undesirable. The conversion of SO2 to SO2CI2 using CI2, on the other hand, naturally requires a specific production system to be set up. There is therefore a need to improve the reaction step from the compound of formula (II) to the compound of formula (III) so that the advantages of carrying out the process with SO2CI2 can be exploited without being confronted with the mentioned problems of waste. According to the invention, it has been possible, surprisingly, to solve the problem by simple means. In this respect, it is mentioned in EP-A-446 913, Example 1, that when the compound of formula (lla) is chlorinated in chloroform there is first formed a mixture of intermediates, the structures of which are postulated as being That mixture of intermediates is allowed to react completely, with cooling at about +40°C, to form the compound of formula (III). It has now been found that, in the case of that procedure, a dangerous heating potential, inter alia, is built up, which in an unfavourable case may result in a major incident. In a particular embodiment of the process according to the invention, that problem is avoided by carrying out the reaction continuously, only small amounts of the said intermediates being accumulated per unit of time and, moreover, the residence times in the individual reactors being short. Some compounds of formulae (I) to (IV) cantain asymmetric carbon atoms, as a result of which the compounds may occur in optically active forms. Formulae (I) to (IV) are intended to include all those possible isomeric forms, and mixtures thereof, for example racemates or mixtures of E/Z isomers. The general terms used hereinbefore and hereinafter have the following meanings, Unless defined otherwise: Unless otherwise defined, carbon-containing groups and compounds each contain from 1 up to and including 8, preferably from 1 up to and including 6, especially from 1 up to $nd including 4, and more especially 1 or 2, carbon atoms. Alkyl, both as a group perse and as a structural element of other groups and compounds, for example haloalkyi, arylalkyi and hydroxyalkyi, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl. Alkenyl, both as a group perse and as a structural element of other groups and compounds, for example haloalkenyl and arylalkenyl, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, for example vinyl, 1-methylvinyl, allyl, 1-butenyl or 2-hexenyl, or branched, for example isopropenyl. Alkynyl, both as a group per se and as a structural element of other groups and compounds, for example haloalkynyl, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, for example propargyl, 2-butynyl or 5-hexynyl, or branched, for example 2-ethynyl-propyl or 2-propargylisopropyl. Ca-CeCycloalkyI is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especially cyclohexyl. Aryl is phenyl or naphthyl, especially phenyl. Heteroaryl is to be understood as being a five- to seven-membered monocyclic aromatic ring having from one to three hetero atoms selected from the group consisting of N, O and S, especially N and S, or a bicyclic heteroaryl that may contain either in only one ring -as for example, in quinolinyl, quinoxalinyl, indolinyl, benzothiophenyl or benzofuranyl - or in boith rings - as, for example, in pteridinyl or purinyl - independently of one another one or more hetero atoms selected from N, O and S. Preference is given to pyridyl, pyrimidinyl, tihiazolyl and benzothiazolyl. Halogen, both as a group perse and as a structural element of other groups and compounds, for example haloalkyi, haloalkenyl and haloalkynyl, is fluorine, chlorine, bromine or iodine, especially fluorine, chlorine or bromine, more especially chlorine or bromine, and very especially chlorine. Halo-substituted, carbon-containing groups and compounds, for example haloalkyi and haloalkenyl, may be partially halogenated or perhalogenated, the halogen substituents in the case of multiple halogenation being identical or different. Examples of haloalkyi, both as a group perse and as a structural element of other groups and compounds, for example haloalkenyl, are methyl mono- to tri-substituted by fluorine, chlorine and/or by bromine, for example CHF2 or CF3; ethyl mono- to penta-substituted by fluorine, chlorine and/or by bromine, for example CH2CF3, CF2CF3. CF2CCI3, CF2CHCI2, CF2CHF2, CF2CFCI2, CFsCHBra, CF2CHCIF, CFsCHBrF or CCIFCHCIF; propyl or isopropyl each mono- to hepta-substituted by fluorine, chlorine and/or by bromine, for example CH2CHBrCH2Br, CF2CHFCF3, OH2CF2CF3 or CH(CF3)2; and butyl, or one of the isomers thereof, mono- to nona-substituted by fluorine, chlorine and/or by bromine, for example CF(CF3)CHFCF3 or CH2(CF2)2CF3. Haloalkenyl is, for example, CH2CH=CHCI, CHsCH^CCb. CH2CF=CF2 or CH2CH=CHCH2Br. Some compounds of formulae (I) to (IV) may be in the form of tautomers. Those compounds are therefore to be understood hereinbefore and hereinafter as including corresponding tautomers, even if the latter are not specifically mentioned in each case. Compounds of formulae (I) to (IV) having at least one basic centre are capable, for example, of forming acid addition salts. Those acid addition salts are formed, for example, with strong inorganic acids, such as mineral acids, e.g. perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic aicids, such as unsubstituted or substituted, e.g. halo-substituted, Ci-Caalkanecarboxylic acids, e.g. acetic acid, saturated or unsaturated dicarboxylic acids, e.g. oxalic, malonic, succinic, maleic, fumaric and phthalic acid, hydroxycarboxylic acids, e.g. ascorbic, lactic, nnalic, tartaric and citric acid, or benzoic acid, or with organic sulfonic acids, such as unsubstituted or substituted, e.g. halo-substituted, C1-C4alkane- or aryl-sulfonic acids, e.g. nnethane- or p-toluene-sulfonic acid. Furthermore, compounds of formulae (I) to (IV) having at least one acid group are capable of forming salts with bases. Suitable salts with bases are, for example, metal salts, such as alkali metal and alkaline earth metal salts, e.g. sodium, potassium and magnesium salts, and salts with ammonia or an organic amine, such sis morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkylamine, e.g. ethyl-, diethyl-, triethyl- or dimethyl-propyl-amine, or a mono-, di- or tri-hydroxy-lower alkylamine, e.g. mono-, di- ortri-ethanolamine. In addition, corresponding internal salts may optionally also be formed. The compounds of formulae (I) to (IV) are to be understood hereinbefore and hereinafter as including both the compounds of formulae (I) to (IV) in free form and the corresponding salts. The same is correspondingly true for tautomers of compounds of formulae (I) to (IV) and salts thereof. In the case of the compounds of formulae (I) and (III), preference is generally given in each case to a process for the preparation of the free form. Preference is given within the scope of the invention to a process for the preparation of a compound of formula (I) (1) wherein R1 and R2 in the compounds of formulae (I) and (IV) either are each independently of the other hydrogen or C1-C4alkyl or together are a two- or three-membered alkylene bridge which optionally contains a hetero atom from the group consisting of NR5, 0 and S, and R5 is H or C1-C4alkyl; and especially are hydrogen or together are a two- or three-membered alkylene bridge which optionally contains a hetero atom from the group consisting of NR5 and O, and R5 is C1-C4alkyl; and more especially R1 and R2 together are -CH2-O-CH2-, -CH2-CH2-CH2- or -CH2-CH2-I (2) wherein Q is N; (3) wherein Y is NO2; (4) wherein Z is NR3 and R3 is H or C1-C4alkyl; (5) wherein, in process step a), the reaction temperature is in the range from -30°C to 100°C, preferably from 0°C to 50°C, especially from 20°C to 45°C; (6) wherein the reaction according to process step a) is carried out in acetonitrile in a temperature range from 0°C to 30°C, preferably at 20°C; (7) wherein X in the compound of formula (II) is halogen such as fluorine, chlorine, bromine or iodine, -0-C(=0)-A, .0-P(=0)(-A)2, -0-S(=0)2A, -S-P(=0)(-A)2, -S-P(=S)(-A)2, -S(=0)A or -S(=0)2A, wherein A is unsubstituted or substituted Ci-CsalkyI, C2-C8alkenyl or Ca-Cealkynyl, unsubstituted or substituted aryl, unsubstituted or substituted benzyl, GrCaalkoxy or di(Ci-C8alkyl)amine wherein the alkyl groups are independent of one another; especially wherein X is chlorine, bromine or iodine, more especially chlorine or bromine; very especially wherein X is chlorine; (8) wherein SO2 is used in an amount of from 1 mo! % to 50 mo! %, preferably from 10 mol % to 40 mol %, especially from 15 mol % to 30 mol %, based on the starting material of formula (II); (9) wherein SO2 is used in the form of SO2 gas or in the form of an S02-releasing agent, preferably SO2CI2; (10) wherein in process step a) a continuous procedure is employed. Especially suitable process conditions can be found in the Examples. The process is especially suitable for the preparation of thiamethoxam, known from WO 98/32747; and of Ti-435 (clothianidin), known from EP-A-446 913. Process step a): The reaction of process step a) described hereinbefore and hereinafter is carried out, if necessary, in a closed vessel, under pressure, in an inert gas atmosphere and/or under anhydrous conditions. Especially advantageous reaction conditions can be found in the Examples. The reactants can be reacted with one another as such, i.e. without a solvent or diluent, for example in molten form. In most cases, however, the addition of a solvent or diluent is advantageous. Suitable solvents include aprotic solvents, especially, for example: aliphatic, aromatic and alicyclic hydrocarbons, such as benzene, toluene, xylene, mesitylene, Tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane, trichloroethene and tetrachloroethene; esters, such as ethyl acetate, methyl acetate, dimethyl carbonate, diethyl carbonate, methyl formate, ethyl formate, ethoxyethyl acetate and methoxyethyl acetate; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether,, t$trahydrofuran and dioxane; ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone; amides, such as N,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and hexamethyl-plhosphoric acid triamide; nitriles, such as acetonithle and propionitrile; and sulfoxides, such as dimethyl sulfoxide; nitroalkanes and aromatic nitro compounds, such as nitromethane, nitroethane and nitrobenzene; or mixtures of such solvents. Preference is given to polar aiprotic solvents, especially carboxylic acid derivatives such as amides and nitriles; especially preferred solvents can be found in the Examples. Suitable chlorinating agents include especially chlorine, POCI3, PCI3, PCI5 and SO2CI2; more especially chlorine or S02Cl2, very especially a mixture of chlorine and SO2CI2. Catalytic amounts are to be understood as less-than-stoichiometric amounts based on the starting material of formula (II). SO2 may either be added as such in gaseous form, or a compound capable of releasing SO2 may be added. SO2CI2 is especially suitable for that purpose. In a preferred variant of process step a), some or all of the SO2CI2 required for the catalysis is first metered in and only then is the chlorinating agent, preferably CI2, added. Process step b): The reactants can be reacted with one another as such, i.e. without the addition of a solvent or diluent, for example in molten form, in most cases, however, the addition of an inert solvent or diluent, or a mixture thereof, is advantageous. Examples of such solvents or diluents that may be mentioned are more or less the same as those mentioned under process step a), although in addition protic solvents, such as alcohols and protic amides, are also suitable. When the reaction in question is carried out in the presence of a base, bases used in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also serve as solvents or diluents. The reaction is carried out preferably at a temperature of from approximately 0°C to approximately +180°C, especially from about +10°C to about +80°C, in many cases between room temperature and the reflux temperature of the solvent. In an especially preferred embodiment of process step b), a compound of formula (IV) is reacted at from 0°C to 120'C, especially from 20X to SOX, preferably from 30°C to 60X, in an ester, especially in dimethyl carbonate, and preferably in the presence of a base, especially K2CO3. The reaction is preferably carried out at normal pressure. The reaction time is not critical; preference is given to a reaction time of from 0.1 to 48 hours, especially from 0.5 to 12 hours. The product is isolated by the usual methods, for example by filtration, crystallisation, distillation or chromatography or any suitable combination of such methods. The yields achieved are usually good. It is often possible to obtain a yield of 80 % of the theoretical value. Preferred conditions under which the reaction is carried out can be found in the Examples. Salts of compounds of formulae (I) to (IV) can be prepared in a manner known perse. For example, acid addition salts are obtained by treatment with a suitable acid or a suitable ion exchange reagent and salts with bases by treatment with a suitable base or a suitable ion exchange reagent. Salts of compounds of formulae (I) to (IV) can be converted into the free compounds of formulae (I) to (IV) in customary manner; acid addition salts can be converted, for example, by treatment with a suitable basic medium or a suitable ion exchange reagent and salts with bases, for example, by treatment with a suitable acid or a suitable ion exchange reagent. Salts of compounds of formulae (I) to (IV) can be converted into different salts of compounds of formulae (I) to (IV) in a manner known perse] for example, acid addition salts can be converted into different acid addition salts, for example by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt being formed, for example silver chloride, is insoluble and is therefore precipitated out from the reaction mixture. Depending upon the procedure and/or the reaction conditions, the compounds of formulae (I) to (IV) having salt-forming properties can be obtained in free form or in the form of salts. The compounds of formulae (I) to (IV) and, in each case, where applicable, the tautomers thereof, in each case in free form or in salt form, may be in the form of one of the possible isomers or in the form of a mixture thereof, for example depending upon the number of asymmetric carbon atoms occurring in the molecule and the absolute and relative configuration thereof and/or depending upon the configuration of non-aromatic double bonds occurring in the molecule, in the form of pure isomers, such as antipodes and/or diastereo-isomers, or in the form of mixtures of isomers, such as mixtures of enantiomers, for example racemates, mixtures of diastereoisomers or mixtures of racemates; the invention relates both to the pure isomers and to all possible mixtures of isomers and this is to be understood accordingly hereinbefore and hereinafter, even when stereochemical details are not specifically mentioned in each case. Mixtures of diastereoisomers or mixtures of racemates of compounds of formulae (I) to (l:V), or salts thereof, obtainable in accordance with the process - depending upon the starting materials and procedures chosen - or by other means can be separated into the pure diastereoisomers or racemates in known manner on the basis of the physico-chemical differences between the constituents, for example by fractional crystallisation, distillation and/or chromatography. Mixtures of enantiomers, such as racemates, so obtainable can be separated into the optical antipodes by known methods, for example by recrystallisation from an optically active solvent, by chromatography on chiral adsorbents, for example high-pressure liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific immobilised enzymes, vai the formation of inclusion compounds, for example using chiral crown ethers, in which case only one enantiomer is complexed, or by conversion into diastereoisomeric salts, for example by reacting a basic end product racemate with an optically active acid, such as a carboxylic acid, for example camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example camphorsulfonic acid, and separating the mixture of diastereoisomers obtainable in that manner, for example on the basis of their different solubilities by fractional crystallisation, into the diastereoisomers, from which the desired enantiomer can be freed by the action of suitable, for example basic, media. Pure diastereoisomers and enantiomers can be obtained not only by separation of corresponding mixtures of isomers but also, according to the invention, by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials that have appropriate stereochemistry. The compounds of formulae (I) to (IV), and salts thereof, may also be obtained in the form of hydrates and/or may include other solvents, for example solvents that may optionally have been used for the crystallisation of compounds that occur in solid form. The invention relates to all those embodiments of the process according to which a compound obtainable as starting material or intermediate at any stage of the process is used as starting material and all or some of the remaining steps are carried out, or in which a starting material is used in the form of a derivative or a salt and/or its racemates or antipodes, or, especially, is formed under the reaction conditions. Compounds of formulae (I), (III) and (IV) obtainable in accordance with the process or by other means can be converted into different corresponding compounds in a manner known per se. In the processes of the present invention there are preferably used those starting niaterials and intermediates, in each case in free form or in salt form, which result in the compounds of formula (I) or salts thereof described at the beginning as being especially valuable. The invention relates especially to the preparation processes described in the Examples. The present invention relates also to the process for the preparation of a compound of formula (III) from a compound of formula (II) according to process step a) as defined hereinbefore. The preferences applying to the substituents of compounds of formula (IV) are the same as those mentioned hereinbefore in the processes for the preparation of compounds of formula (I). The compounds of formulae (II) and (IV) are known, for example as intermediates for the preparation of pesticides, or they can be prepared using processes known perse. Preparation Examples A) Preparation of 2-chloro-5-chloromethvl-thiazole Example P1: 10 g of SO2 are introduced at 20°C into a solution of 73 g of 2-chloro-3-isothiocyanato-1-propene in 133 g of chlorobenzene. Then, over the course of 6 hours, 45 g of chlorine are introduced under the surface. The reaction mixture is then heated to 50°C, which is maintained until the evolution of gas ceases. There are obtained 232 g of a solution which, according to gas chromatographic analysis, contains 29.4 % 2-chloro-5-chloromethyl-tlhiazole by weight. Yield: 81.3 % of theory, based on 2-chloro-3-isothiocyanato-1-propene. Example P2: In an analogous experiment, 49 g of chlorine are used without the catalyst, the other amounts of chemicals used and the reaction parameters being left the same as in Example 1. There are obtained 236 g of a solution which, according to gas chromatographic analysis, contains 20.9 % 2-chloro-5-chloromethyl-thiazole by weight. Yield: 58.5% of theory, based on 2-chloro-3-isothiocyanato-1-propene. Example P3: 35 g of SO2 are introduced, at 30°C, into a solution of 509 g of 2-chloro-3-isothiocyanato-1-propene in 931 g of chlorobenzene. Then, over the course of 6 hours, 290 g of chlorine are introduced under the surface. The reaction mixture is heated to 50'C and is then stirred until the evolution of gas ceases. A vacuum of 120 mbar is then applied and maintained for one hour. By that means there are obtained 1589 g of a solution which, according to gas chromatographic analysis, contains 30.8 % of 2-chloro-5-chloromethyl-thiazole by weight. Yield: 83.2 % of theory, based on 2-chloro-3-isothiocyanato-1-propene. Distillation of 1571 g of the resulting crude solution at 75°C and an internal pressure of 5 mbar yields 488.2 g of a material which contains 94.5 % 2-chloro-5-chloromethyl-thiazole by weight. Example P4: 21 g of SO2CI2 are introduced, at 20°C, into a solution of 146 g of 2-chloro-3-isothiocyanato-1-propene in 266 g of chlorobenzene. Then, at 40°C, 69 g of chlorine are introduced under the surface over the course of 5 hours. The reaction mixture is heated to 50°C and is then stirred until the evolution of gas ceases. A vacuum of 120 mbar is then applied and maintained for one hour. There are obtained 441 g of a solution which, according to gas chromatographic analysis, contains 31.2 % 2-chloro-5-chloromethyl-thiazole by weight. Yield: 81.9 % of theory, based on 2-chloro-3-isothiocyanato-1-propene. Example P5: At 20°C, 11 g of SO2 and then, over the course of 6 hours, 82 g of chlorine are introduced under the surface into a solution of 146 g of 2"Chloro-3-isothio-cyanato-1-propene in 266 g of acetonitrile. The reaction mixture is heated to 50°C and is then stirred until the evolution of gas ceases. A vacuum of 580 mbar is applied and maintained for one hour. By that means there are obtained 467 g of a solution which, according to gas chromatographic analysis, contains 32.7 % 2-chIorO"5"Chloromethyl-thiazole by weight. Yield: 90.8 % of theory, based on 2-chloro-3-isothiocyanato-1-propene. Example P6: (continuous reaction procedure) At from 20°C to 22°C, 925 g of a solution containing 33 % (by weight) 2-chloro-3-isothiocyanato-1-propene in acetonitrile, 177.5 g of chlorine and 24.7 g of SO2 are continuously and simultaneously introduced, per hour, into a loop reactor having a volume of 370 ml. The reaction mixture flows over into an after-reactor having an internal temperature of 50°C. Each hour there are obtained from the after-reactor 1086 g of a reaction solution containing 32.2 % 2-chloro-5-chloromethy!-thiazole by weight, which corresponds to a yield of 91.1 % of theory, based on 2-chloro-3-isothiocyanato-1-propene. B) Preparation of 3-(2-chloro-thiazol-5-vl-methvl)-5-methvl-4-nitroimino-perhvdro-1,3,5-oyadiazine Example P7: 184 g of 3-methyl-4-nitroimino-perhydro-1,3,5-oxadiazine 100 % are introduced into 400 g of dimethyl carbonate in a sulfonation flask, and 168 g of 2-chloro-5-chloromethyl-thiazole 100% are added. The mixture is heated to 65'C. While stirring at from 62 to 68°C, a mixture consisting of 350 g of dimethyl carbonate, 4 g of tetramethyl-ammonium hydroxide pentahydrate and 242 g of potassium carbonate powder is metered in over the course of 60 minutes, thorough stirring of the reaction mixture being maintained until more than 99 % of the 2-chloro-5-chloromethylthiazole has been converted. The reaction mixture is then cooled and 600 g of water are added. The pH is adjusted to 6.5 using about 260 g of 32 % hydrochloric acid; the mixture is left to stand until the phases have separated, and the organic phase is separated off. The organic phase is concentrated at 60°C in vacuo to a final weight of 600 g. The mixture is slowly cooled to 0-5°C, which is maintained for one hour. The resulting suspension is then filtered. 218 g of the title product having a purity of from 98 to 99 % (74 % of theory, based on 2-chloro-5-chloromethylthiazole 100 %) are obtained. The invention relates also (B) to a process for the preparation of a compound of formula (I) as defined hereinbefore under (A), wherein c) a compound of formula (II) as defined hereinbefore under (A) is reacted with a chlorinating agent to form a compound of formula or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and d) the compound of formula (111) thereby obtained is reacted with a compound of formula (IV) as defined hereinbefore under (A); in which process the compound of formula (III) is subjected to intermediate purification in a melt crystallisation process; to a process for the preparation of a compound of formula (111) according to process c) hereinbefore, and to the use of the compounds of formulae (II), (III) and (IV) in a process as described hereinbefore. The compounds of formula (1) are known as valuable pesticides, and synthesis nhethods for those compounds are described in the literature. It has, however, been found that especially the compound of formula (III) prepared according to the processes known from the literature does not satisfy the requirements in terms of purity, that it is - probably because of those impurities - thermally unstable, which can in turn lead to significant safety problems in a production plant, and also that the known processes have significant disadvantages in respect of further parameters, for example yield and quality of the end products of formula (1) above, and the like. The known preparation processes are therefore not satisfactory in every respect, which is why there is a need to provide improved preparation processes for the compounds of formula (I) and especially of formula (111). It has now been found that the compound of formula (111) can, using the purification process claimed according to the invention, be prepared, for example, with higher purity and that working with and storing the compound 2-chloro-5"Chloromethylthia2ole are associated with a significantly reduced safety R1sk compared to the processes known from the literature. Purification by melt crystallisation of 2-chloro-5-chloromethylthiazole has several advantages over other purification methods. Because 2-chloro-5-chloromethylthiazole is thermally unstable and, in addition, has a "thermal memory", which means that the compound becomes more unstable with increasing thermal stress, any kind of thermal stress Should be avoided as far as possible. Moreover, in the case of distillative purification, for example, it is not readily possible for all subsidiary products to be separated. Distillative purification requires columns having high numbers of plates, which requires a higher distillation temperature, combined with the correspondingly greater loss of product and reduced thermal safety of the distillation process. Melt crystallisation normally yields at least 98 % pure 2-chloro-5-chloromethylthiazole. It is also possible for the mother liquor to be recycled in order to recover the 2-chloro-5-chloromethylthiazole present therein. Melt crystallisation moreover offers the advantage that the R1sk of corrosion to the apparatus is minimised because of the low working temperatures and, furthermore, that neither solvents nor other additives are employed in the process. Preference is given within the scope of the invention (B) to a process for the preparation of a compound of formula (I) (1) wherein R1 and Rg in the compounds of formulae (I) and (IV) together are -CH2-O-CH2-, -CH2-CH2-CH2- or -CH2-CH2-; (2) wherein Q is N; (3) wherein Y is NO2; (4) wherein Z is NR3 and R3 is H or C1-C4alkyl; (5) wherein the purification step is carried out in process step a) at from CC to +25°C, especially at from +5°C to H-15C; , (6) wherein X in the compound of formula (II) is halogen such as fluorine, chlorine or bromine; especially chlorine or bromine, more especially wherein X is chlorine; K (7) wherein, in process step c), there is used an aprotic polar solvent having a dielectric constant greater than 10; especially greater than 20; more especially greater than 25; very especially greater than 30; (8) wherein, in process step c), there is used as solvent a carboxylic acid nitrile, e.g. acetonitrile, propionitrile or butyronitrile; a carboxylic acid amide, e.g. formamide, N-methyl-formamide, N,N-dimethylformamide, N-methylacetamide, N,N-dimethylacetamide or 1-methylpyrrolidin-2-one; a carbonic acid ester, e.g. propylene carbonate; a nitroalkane, e.g. nitromethane or nitroethane; nitrobenzene; a sulfoxide, e.g. dimethylsulfoxide; sulfolane; hexamethylphosphoric acid triamide; 1,3-dimethylimidazolidin-2-one; a urea derivative, e.g. tetramethylurea; or an ether, e.g. dioxane, tetrahydrofuran. ethylene glycol dimethyl ether or dimethoxydiethyl ether; or mixtures of such solvents; (9) wherein as halogenating agent there is used Cl2, a mixture of CI2 and SO2 or a niixture of CI2 and S02Cl2; especially wherein chlorination is performed using CI2, and SO2 or SO2CI2 is used in catalytic amounts, more especially wherein SO2 or SO2CI2 is used in an amount of from 10 to 40 mol %, based on the starting material of formula (II); (10) wherein in process step c) a continuous procedure is employed for the preparation of the crude compound of formula (III). The process is especially suitable for the preparation of thiamethoxam, known from WO 98/32747; and of Ti-435 (clothianidin), known from EP-A-446 913. The dielectric constants of suitable solvents can be found, for example, in C. Reichardt, Solvents and Solvent Effects, VCH Verlagsgesellschaft, Weinheim, 1988, Table A-1, pages 408 to 410. The temperatures at which those values apply can also be found in the said table. Othenwise, the conditions applying to process steps c) and d) are the same as those set out under invention statement (A) for process steps a) and b). Salts of compounds of formulae (I) to (IV) can be prepared in a manner known perse as mentioned hereinbefore under invention statement (A). Salts of compounds of formulae (I) to (IV) can also be converted into the free compounds of formulae (I) to (IV) in conventional manner as mentioned hereinbefore under invention statement (A). Salts of compounds of formulae (I) to (IV) can be converted into different salts of compounds of formulae (I) to (IV) in a manner known perse. The compounds of formulae (I) to (IV), and salts thereof, may also be obtained in the form of hydrates and/or may include other solvents, for example solvents that may optionally have been used for the crystallisation of compounds that occur in solid form. The invention relates to all those embodiments of the process according to which a compound obtainable as starting material or intermediate at any stage of the process is used as starting material and all or some of the remaining steps are carried out, or in which a starting material is used in the form of a derivative or a salt and/or its racemates or antipodes, or, especially, is formed under the reaction conditions. Compounds of formulae (I), (III) and (IV) obtainable in accordance with the process or by other means can be converted into different corresponding compounds in a manner Known perse. In the process of the present invention there are preferably used those starting materials and intermediates, in each case in free form or in salt form, which result in the compounds of formula (I) or salts thereof described at the beginning as being especially valuable. The present invention relates also to a melt crystallisation process for purification of a compound of formula (III). An especially preferred aspect of the invention is a continuous purification process for the compound of formula (III), for example by means of a fluid bed which has a temperature gradient. The invention relates especially to the preparation processes described in the Examples. The preferences applying to the substituents of compounds of formula (IV) are the same those mentioned hereinbefore in the processes for the preparation of compounds of formula (I). The compounds of formulae (II) and (IV) are known, for example as intermediates for the preparation of pesticides, or they can be prepared using processes known perse. Preparation Examples Example P8: At 20°C, 143.2 g of sulfuryl chloride are metered into a solution of 147.5 g of 2-chloro-3HSOthiocyanato-1-propene in 150 g of acetonitrile over the course of about 2 hours. The reaction is slightly exothermic. Towards the end of the reaction, the solution is heated to 40°C and is maintained at that temperature for one hour, during which marked evolution of gas can be observed. The solvent, together with the hydrochloric acid, is concentrated in vacuo. 187.0 g of a 77 % solution of 2-chloro-5-chloromethyl-thiazole are obtained, which corresponds to a yield of 86 % of theory, based on 2-chloro-3-isothio-cyanato-1 -propene. Example P9: At 20°C, 67.5 g of 2-chloro-3-isothiocyanato-1 -propene are introduced into 75 ml of dimethylformamide, and 6.8 g of sulfuryl chloride (0.05 mol) are added to the neaction mixture. 32.5 g of chlorine are then introduced over the course of about 2 hours until an excess of starting material can no longer be detected. After the addition is complete, the reaction solution is heated to SOX and maintained at that temperature for one hour. Finally, the HCI formed and the solvent are drawn off in vacuo. 2-Chloro-5-chloromethyl-thia2ole having a content of 72 % is obtained. Example P10: At 20X, 87.7 g of 2-chloro-3-isothiocyanato-1-propene are introduced into 100 ml of nitromethane. 41.5 g of chlorine are then introduced over the course of about 2 hours until an excess of starting material can no longer be detected. The reaction solution is then stirred at 40°C for one hour and is cooled again. The HCI is drawn off in vacuo and the nitromethane is distilled off. 2-Chloro-5-chloromethyl-thiazole having a content of 91 % is obtained. The product contains approximately 1 % of the subsidiary product of formula Example P11: 166.6 g of 2-chloro-3-isothiocyanato-propene are introduced into 300 g of 1,2-dichloroethane in a double-walled reactor. At 30°C, 78 g of chlorine are introduced over the course of 4-5 hours. The reaction mixture is then heated to 60°C, which is maintained for 60 minutes until the evolution of gas (HCI) has ceased. The reaction mixture is then cooled to room temperature and 200 g of 37 % hydrochloric acid are added, with stirring. After the phases have separated, the organic phase is extracted a further four times using 100 g of 37 % hydrochloric acid each time. The aqueous extracts, which contain the product, are combined, 800 g of water are added and extraction using five portions of 1,2-dichloroethane totalling 500 g is carried out. The extracts are combined and the solvent is evaporated off. A crude melt having a content of about 92 % is obtained. Example PI 2: 2,5 kg of liquid 2-chloro-5-chloromethyI-thiazole having a content of 95 % are cooled to 10°C in a glass beaker, provided with a seed crystal and left to stand at 10°C for 5 hours. A two-phase mixture having a brown, liquid, upper phase and a crystalline lower phase is formed. The liquid phase is separated off and the solid phase is transferred to a filter and allowed to drain for one hour. 2.3 kg of the title product are obtained in the form of white needles having a content of more than 99 % and a melting point of from 28°C to 29°C. Example P13: 3-(2-ChlorQ-thiazol-5-vl-methvl)-5-methvl-4-nitroimino-perhvdro-1,3,5-Qxadiazine: 184 g of 3-methyI-4-nitroimino-perhydro-1,3,5-oxadiazine 100 % are introduced irito 400 g of dimethyl carbonate in a sulfonation flask and 170 g of 2-chloro-5-chloro-methylthiazole having a content of 99 % are added. The mixture is heated to 65°C. While stirring at from 62°C to 68°C. a mixture consisting of 350 g of dimethyl carbonate, 4 g of tetramethylammonium hydroxide pentahydrate and 242 g of potassium carbonate powder are metered in over the course of 60 minutes, thorough stirring of the reaction mixture being maintained until more than 99 % of the 2-chloro-5-chloromethylthiazole have been converted (monitored by LC). The reaction mixture is then cooled and 600 g of water are added. The pH is adjusted to 6,5 using about 260 g of 32 % hydrochloric acid; the mixture is left to stand until the pjhases have separated, and the organic phase is separated off. The organic phase is concentrated at 60°C in vacuo to a final weight of 600 g. The mixture is slowly cooled to 0-5°C, which is maintained for one hour. The resulting suspension is then filtered. 218 g of title product having a purity of from 98 to 99 % (74 % of theory, based on 2-chloro-5-chloromethylthiazole 100 %) are obtained. WE CLAIM: 1. A process for the preparation of a compound of formula and, where appropriate, an E/Z isomer, a mixture of E/Z isomers and/or a tautomer thereof, in each case in free form or in salt form, wherein Q is CH or N; Y is NO2 OR CN; Z is CHR3, O, NR3 or S; Ri and R2 either are each independently of the other hydrogen or CpCgalkyl which is unsubstituted or substituted by R4 or together are an alkylene bridge having two or three carbon atoms which optionally contains a hetero atom selected from the group consisting of NR5, O and S, R3 is H or C1-C12alkyl which is unsubstituted or substituted by R4, R4 is unsubstituted or substituted aryl or heteroaryl, and R5 is H or C1-C12alkyl; wherein a) a compound of formula wherein X is a leaving group, is reacted with a chlorinating agent at a temperature of 0°C to 50°C using chlorine, POCI3, PCI3, PCI5 or SO2CI2 or a mixture of chlorine and SO2CI2 as chlorinating agent to form a compound of formula or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and b) the compound of formula (III) thereby obtained is reacted at a temperature of 10°C to 80°C in the presence of a base with a compound of formula wherein Ri, R2, Y, Z and Q are as defined hereinbefore for the compound of formula (I); in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of a catalytic amount of SO2. 2. The process as claimed in claim 1, wherein the process step a) is carried out in acetonitrile. 3. The process according to any one of claims 1 or 2, wherein in process step a) SO2 is used in an amount of from 1 mol % to 50 mol %, based on the starting material of formula (II). 4. The process for the preparation of a compound of formula wherein a compound of formula wherein X is a leaving group, or, where appropriate, a tautomer thereof, in each case in free form or in salt form, is reacted with a chlorinating agent; in which process the chlorination is performed in the presence of a catalytic amount of SO2. 5. The process for the preparation of a compound of formula (I) as claimed in claim 1, wherein the intermediate compound of formula (III) is purified by melt crystallization.

Full Text

The invention relates to a process for the preparation of thiazole derivatives. (A) to a process for the preparation of a compound of formula
and, where appropriate, E/Z isomers, mixtures of E/Z isomers and/or tautomers
thereof, in each case in free form or in salt form, wherein
Q is CH or N;
Y is NO2 or CN
Z is CHR3, O, NR3 or S;
R1 and R2 either are each independently of the other hydrogen or C1-C8-alkyl which is unsubstituted or substituted by R4 or together are an alkylene bridge having two or three carbon atoms which optionally contains a hetero atom selected from the group consisting of NR5, O and S,
R3 is H or C1-C12-alkyl which is unsubstituted or substituted by R4,
R4 is unsubstituted or substituted aryl or heteroaryl, and
R5 is H or C1C12-alkyl wherein
a) a compound of formula

which is known or which can be prepared by known methods and wherein X is a leaving group, is reacted with a chlorinating agent to form a compound of formula

or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and
b) the compound of formula (III) thereby obtained is reacted with a compound of
formula

which is known or which can be prepared by methods known perse and wherein Ri, R2. Y. Z and Q are as defined hereinbefore for the compound of formula (I);
in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of catalytic amounts of SO2;
to a process for the preparation of a compound of formula (III) according to process step a) hereinbefore, and to the use of compounds of formulae (II), (III) and (IV) in a process as described hereinbefore.
The compounds of formula (I) are known as valuable pesticides, and synthesis rriethods for those compounds are described in the literatuje. It has, however, been found that significant safety problems occur in the case of those processes known from the literature. It has moreover been found that the compound of formula (III) prepared according to the known processes does not satisfy the requirements in terms of purity either, that it isl - probably because of those impurities - thermally unstable, which in turn can lead to significant problems in a production plant, and also that the known processes have significant disadvantages in respect of further parameters, for example yield, duration of the synthesis cycle, volume yield, disposal of ecologically and toxicologically problematic wastes, for example solvents, SO2, and the like.
The known preparation processes are therefore not satisfactory in every respect, which is why there is a need to provide improved preparation processes for the compounds of formula (I) and especially of formula (III).
In Example 1 of EP-A-446 913, the compound of formula (II) hereinbefore is reacted with chlorine, 2-chloro-5-chloromethyl-thiazole of formula (III) above being obtained in a crude yield of 73 %. In Example 2 of EP-A-446 913, the same reaction is carried out, but using SO2CI2 instead of chlorine. The crude yield in that Example is 82 %. The content of 2-chloro-5-chloromethyl-thiazole is not mentioned in Example 1 of EP-A-446 913. In Example 2, a content of slightly more than 90 % 2-chloro-5-chloromethyl-thiazole is mentioned, from which it is possible to deduce a yield of about 74 % of theory. The increased yield in the case of the process using SO2CI, however, is itself a major advantage for production on a large industrial scale: using the method carried out with SO2CI2, more

material can be prepared in the same unit of time than when CI2 is employed, certain waste substances are produced in significantly smaller amounts by that means, and there are further advantages besides. However, the use of SO2CI2 has the significant disadvantage that stoichiometric amounts of SO2 are produced, which have to be removed, either by recycling the SO2 to SO2CI2 using CI2 or by having to convert the SO2 into S042 by oxidation. However, S042 is a waste substance which, although not ecologically harmful, seriously attacks the concrete walls of waste water purification systems and is therefore extremely undesirable. The conversion of SO2 to SO2CI2 using CI2, on the other hand, naturally requires a specific production system to be set up. There is therefore a need to improve the reaction step from the compound of formula (II) to the compound of formula (III) so that the advantages of carrying out the process with SO2CI2 can be exploited without being confronted with the mentioned problems of waste. According to the invention, it has been possible, surprisingly, to solve the problem by simple means.
In this respect, it is mentioned in EP-A-446 913, Example 1, that when the compound of formula
(lla) is chlorinated in chloroform there is first formed a mixture of intermediates, the structures of which are postulated as being

That mixture of intermediates is allowed to react completely, with cooling at about +40°C, to form the compound of formula (III). It has now been found that, in the case of that procedure, a dangerous heating potential, inter alia, is built up, which in an unfavourable case may result in a major incident. In a particular embodiment of the process according to the invention, that problem is avoided by carrying out the reaction continuously, only small amounts of the said intermediates being accumulated per unit of time and, moreover, the residence times in the individual reactors being short.

Some compounds of formulae (I) to (IV) cantain asymmetric carbon atoms, as a result of which the compounds may occur in optically active forms. Formulae (I) to (IV) are intended to include all those possible isomeric forms, and mixtures thereof, for example racemates or mixtures of E/Z isomers.
The general terms used hereinbefore and hereinafter have the following meanings, Unless defined otherwise:
Unless otherwise defined, carbon-containing groups and compounds each contain from 1 up to and including 8, preferably from 1 up to and including 6, especially from 1 up to $nd including 4, and more especially 1 or 2, carbon atoms.
Alkyl, both as a group perse and as a structural element of other groups and compounds, for example haloalkyi, arylalkyi and hydroxyalkyi, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl.
Alkenyl, both as a group perse and as a structural element of other groups and compounds, for example haloalkenyl and arylalkenyl, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, for example vinyl, 1-methylvinyl, allyl, 1-butenyl or 2-hexenyl, or branched, for example isopropenyl.
Alkynyl, both as a group per se and as a structural element of other groups and compounds, for example haloalkynyl, is, in each case taking due account of the particular number of carbon atoms contained in the group or compound in question, either straight-chained, for example propargyl, 2-butynyl or 5-hexynyl, or branched, for example 2-ethynyl-propyl or 2-propargylisopropyl.
Ca-CeCycloalkyI is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especially cyclohexyl.
Aryl is phenyl or naphthyl, especially phenyl.
Heteroaryl is to be understood as being a five- to seven-membered monocyclic aromatic ring having from one to three hetero atoms selected from the group consisting of N, O and S, especially N and S, or a bicyclic heteroaryl that may contain either in only one ring -as for example, in quinolinyl, quinoxalinyl, indolinyl, benzothiophenyl or benzofuranyl - or in boith rings - as, for example, in pteridinyl or purinyl - independently of one another one or

more hetero atoms selected from N, O and S. Preference is given to pyridyl, pyrimidinyl, tihiazolyl and benzothiazolyl.
Halogen, both as a group perse and as a structural element of other groups and compounds, for example haloalkyi, haloalkenyl and haloalkynyl, is fluorine, chlorine, bromine or iodine, especially fluorine, chlorine or bromine, more especially chlorine or bromine, and very especially chlorine.
Halo-substituted, carbon-containing groups and compounds, for example haloalkyi and haloalkenyl, may be partially halogenated or perhalogenated, the halogen substituents in the case of multiple halogenation being identical or different. Examples of haloalkyi, both as a group perse and as a structural element of other groups and compounds, for example haloalkenyl, are methyl mono- to tri-substituted by fluorine, chlorine and/or by bromine, for example CHF2 or CF3; ethyl mono- to penta-substituted by fluorine, chlorine and/or by bromine, for example CH2CF3, CF2CF3. CF2CCI3, CF2CHCI2, CF2CHF2, CF2CFCI2, CFsCHBra, CF2CHCIF, CFsCHBrF or CCIFCHCIF; propyl or isopropyl each mono- to hepta-substituted by fluorine, chlorine and/or by bromine, for example CH2CHBrCH2Br, CF2CHFCF3, OH2CF2CF3 or CH(CF3)2; and butyl, or one of the isomers thereof, mono- to nona-substituted by fluorine, chlorine and/or by bromine, for example CF(CF3)CHFCF3 or CH2(CF2)2CF3. Haloalkenyl is, for example, CH2CH=CHCI, CHsCH^CCb. CH2CF=CF2 or CH2CH=CHCH2Br.

Some compounds of formulae (I) to (IV) may be in the form of tautomers. Those compounds are therefore to be understood hereinbefore and hereinafter as including corresponding tautomers, even if the latter are not specifically mentioned in each case.
Compounds of formulae (I) to (IV) having at least one basic centre are capable, for example, of forming acid addition salts. Those acid addition salts are formed, for example, with strong inorganic acids, such as mineral acids, e.g. perchloric acid, sulfuric acid, nitric

acid, nitrous acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic aicids, such as unsubstituted or substituted, e.g. halo-substituted, Ci-Caalkanecarboxylic acids, e.g. acetic acid, saturated or unsaturated dicarboxylic acids, e.g. oxalic, malonic, succinic, maleic, fumaric and phthalic acid, hydroxycarboxylic acids, e.g. ascorbic, lactic, nnalic, tartaric and citric acid, or benzoic acid, or with organic sulfonic acids, such as unsubstituted or substituted, e.g. halo-substituted, C1-C4alkane- or aryl-sulfonic acids, e.g. nnethane- or p-toluene-sulfonic acid. Furthermore, compounds of formulae (I) to (IV) having at least one acid group are capable of forming salts with bases. Suitable salts with bases are, for example, metal salts, such as alkali metal and alkaline earth metal salts, e.g. sodium, potassium and magnesium salts, and salts with ammonia or an organic amine, such sis morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkylamine, e.g. ethyl-, diethyl-, triethyl- or dimethyl-propyl-amine, or a mono-, di- or tri-hydroxy-lower alkylamine, e.g. mono-, di- ortri-ethanolamine. In addition, corresponding internal salts may optionally also be formed. The compounds of formulae (I) to (IV) are to be understood hereinbefore and hereinafter as including both the compounds of formulae (I) to (IV) in free form and the corresponding salts. The same is correspondingly true for tautomers of compounds of formulae (I) to (IV) and salts thereof. In the case of the compounds of formulae (I) and (III), preference is generally given in each case to a process for the preparation of the free form.
Preference is given within the scope of the invention to a process for the preparation of a compound of formula (I)
(1) wherein R1 and R2 in the compounds of formulae (I) and (IV) either are each
independently of the other hydrogen or C1-C4alkyl or together are a two- or three-membered
alkylene bridge which optionally contains a hetero atom from the group consisting of NR5, 0
and S, and R5 is H or C1-C4alkyl;
and especially are hydrogen or together are a two- or three-membered alkylene bridge which optionally contains a hetero atom from the group consisting of NR5 and O, and R5 is C1-C4alkyl;
and more especially R1 and R2 together are -CH2-O-CH2-, -CH2-CH2-CH2- or -CH2-CH2-I
(2) wherein Q is N;
(3) wherein Y is NO2;
(4) wherein Z is NR3 and R3 is H or C1-C4alkyl;

(5) wherein, in process step a), the reaction temperature is in the range from -30°C to 100°C, preferably from 0°C to 50°C, especially from 20°C to 45°C;
(6) wherein the reaction according to process step a) is carried out in acetonitrile in a temperature range from 0°C to 30°C, preferably at 20°C;
(7) wherein X in the compound of formula (II) is halogen such as fluorine, chlorine, bromine or iodine, -0-C(=0)-A, .0-P(=0)(-A)2, -0-S(=0)2A, -S-P(=0)(-A)2, -S-P(=S)(-A)2, -S(=0)A or -S(=0)2A, wherein A is unsubstituted or substituted Ci-CsalkyI, C2-C8alkenyl or Ca-Cealkynyl, unsubstituted or substituted aryl, unsubstituted or substituted benzyl, GrCaalkoxy or di(Ci-C8alkyl)amine wherein the alkyl groups are independent of one another; especially wherein X is chlorine, bromine or iodine, more especially chlorine or bromine; very especially wherein X is chlorine;
(8) wherein SO2 is used in an amount of from 1 mo! % to 50 mo! %, preferably from 10 mol % to 40 mol %, especially from 15 mol % to 30 mol %, based on the starting material of formula (II);
(9) wherein SO2 is used in the form of SO2 gas or in the form of an S02-releasing agent, preferably SO2CI2;
(10) wherein in process step a) a continuous procedure is employed.
Especially suitable process conditions can be found in the Examples.
The process is especially suitable for the preparation of thiamethoxam, known from WO 98/32747; and of Ti-435 (clothianidin), known from EP-A-446 913.
Process step a):
The reaction of process step a) described hereinbefore and hereinafter is carried out, if necessary, in a closed vessel, under pressure, in an inert gas atmosphere and/or under anhydrous conditions. Especially advantageous reaction conditions can be found in the Examples.
The reactants can be reacted with one another as such, i.e. without a solvent or diluent, for example in molten form. In most cases, however, the addition of a solvent or diluent is advantageous. Suitable solvents include aprotic solvents, especially, for example: aliphatic, aromatic and alicyclic hydrocarbons, such as benzene, toluene, xylene, mesitylene, Tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane,

trichloroethene and tetrachloroethene; esters, such as ethyl acetate, methyl acetate, dimethyl carbonate, diethyl carbonate, methyl formate, ethyl formate, ethoxyethyl acetate and methoxyethyl acetate; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether,, t$trahydrofuran and dioxane; ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone; amides, such as N,N-dimethylformamide, N,N-diethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and hexamethyl-plhosphoric acid triamide; nitriles, such as acetonithle and propionitrile; and sulfoxides, such as dimethyl sulfoxide; nitroalkanes and aromatic nitro compounds, such as nitromethane, nitroethane and nitrobenzene; or mixtures of such solvents. Preference is given to polar aiprotic solvents, especially carboxylic acid derivatives such as amides and nitriles; especially preferred solvents can be found in the Examples.
Suitable chlorinating agents include especially chlorine, POCI3, PCI3, PCI5 and SO2CI2; more especially chlorine or S02Cl2, very especially a mixture of chlorine and SO2CI2.
Catalytic amounts are to be understood as less-than-stoichiometric amounts based on the starting material of formula (II). SO2 may either be added as such in gaseous form, or a compound capable of releasing SO2 may be added. SO2CI2 is especially suitable for that purpose.
In a preferred variant of process step a), some or all of the SO2CI2 required for the catalysis is first metered in and only then is the chlorinating agent, preferably CI2, added.
Process step b):
The reactants can be reacted with one another as such, i.e. without the addition of a solvent or diluent, for example in molten form, in most cases, however, the addition of an inert solvent or diluent, or a mixture thereof, is advantageous. Examples of such solvents or diluents that may be mentioned are more or less the same as those mentioned under process step a), although in addition protic solvents, such as alcohols and protic amides, are also suitable. When the reaction in question is carried out in the presence of a base, bases used in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also serve as solvents or diluents.
The reaction is carried out preferably at a temperature of from approximately 0°C to approximately +180°C, especially from about +10°C to about +80°C, in many cases between room temperature and the reflux temperature of the solvent. In an especially preferred

embodiment of process step b), a compound of formula (IV) is reacted at from 0°C to 120'C, especially from 20X to SOX, preferably from 30°C to 60X, in an ester, especially in dimethyl carbonate, and preferably in the presence of a base, especially K2CO3.
The reaction is preferably carried out at normal pressure.
The reaction time is not critical; preference is given to a reaction time of from 0.1 to 48 hours, especially from 0.5 to 12 hours.
The product is isolated by the usual methods, for example by filtration, crystallisation, distillation or chromatography or any suitable combination of such methods.
The yields achieved are usually good. It is often possible to obtain a yield of 80 % of the theoretical value.
Preferred conditions under which the reaction is carried out can be found in the Examples.
Salts of compounds of formulae (I) to (IV) can be prepared in a manner known perse. For example, acid addition salts are obtained by treatment with a suitable acid or a suitable ion exchange reagent and salts with bases by treatment with a suitable base or a suitable ion exchange reagent.
Salts of compounds of formulae (I) to (IV) can be converted into the free compounds of formulae (I) to (IV) in customary manner; acid addition salts can be converted, for example, by treatment with a suitable basic medium or a suitable ion exchange reagent and salts with bases, for example, by treatment with a suitable acid or a suitable ion exchange reagent.
Salts of compounds of formulae (I) to (IV) can be converted into different salts of compounds of formulae (I) to (IV) in a manner known perse] for example, acid addition salts can be converted into different acid addition salts, for example by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt being formed, for example silver chloride, is insoluble and is therefore precipitated out from the reaction mixture.
Depending upon the procedure and/or the reaction conditions, the compounds of formulae (I) to (IV) having salt-forming properties can be obtained in free form or in the form of salts.

The compounds of formulae (I) to (IV) and, in each case, where applicable, the tautomers thereof, in each case in free form or in salt form, may be in the form of one of the possible isomers or in the form of a mixture thereof, for example depending upon the number of asymmetric carbon atoms occurring in the molecule and the absolute and relative configuration thereof and/or depending upon the configuration of non-aromatic double bonds occurring in the molecule, in the form of pure isomers, such as antipodes and/or diastereo-isomers, or in the form of mixtures of isomers, such as mixtures of enantiomers, for example racemates, mixtures of diastereoisomers or mixtures of racemates; the invention relates both to the pure isomers and to all possible mixtures of isomers and this is to be understood accordingly hereinbefore and hereinafter, even when stereochemical details are not specifically mentioned in each case.
Mixtures of diastereoisomers or mixtures of racemates of compounds of formulae (I) to (l:V), or salts thereof, obtainable in accordance with the process - depending upon the starting materials and procedures chosen - or by other means can be separated into the pure diastereoisomers or racemates in known manner on the basis of the physico-chemical differences between the constituents, for example by fractional crystallisation, distillation and/or chromatography.
Mixtures of enantiomers, such as racemates, so obtainable can be separated into the optical antipodes by known methods, for example by recrystallisation from an optically active solvent, by chromatography on chiral adsorbents, for example high-pressure liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific immobilised enzymes, vai the formation of inclusion compounds, for example using chiral crown ethers, in which case only one enantiomer is complexed, or by conversion into diastereoisomeric salts, for example by reacting a basic end product racemate with an optically active acid, such as a carboxylic acid, for example camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example camphorsulfonic acid, and separating the mixture of diastereoisomers obtainable in that manner, for example on the basis of their different solubilities by fractional crystallisation, into the diastereoisomers, from which the desired enantiomer can be freed by the action of suitable, for example basic, media.
Pure diastereoisomers and enantiomers can be obtained not only by separation of corresponding mixtures of isomers but also, according to the invention, by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the

process according to the invention with starting materials that have appropriate stereochemistry.
The compounds of formulae (I) to (IV), and salts thereof, may also be obtained in the form of hydrates and/or may include other solvents, for example solvents that may optionally have been used for the crystallisation of compounds that occur in solid form.
The invention relates to all those embodiments of the process according to which a compound obtainable as starting material or intermediate at any stage of the process is used as starting material and all or some of the remaining steps are carried out, or in which a starting material is used in the form of a derivative or a salt and/or its racemates or antipodes, or, especially, is formed under the reaction conditions.
Compounds of formulae (I), (III) and (IV) obtainable in accordance with the process or by other means can be converted into different corresponding compounds in a manner known per se.
In the processes of the present invention there are preferably used those starting niaterials and intermediates, in each case in free form or in salt form, which result in the compounds of formula (I) or salts thereof described at the beginning as being especially valuable.
The invention relates especially to the preparation processes described in the Examples.
The present invention relates also to the process for the preparation of a compound of formula (III) from a compound of formula (II) according to process step a) as defined hereinbefore.
The preferences applying to the substituents of compounds of formula (IV) are the same as those mentioned hereinbefore in the processes for the preparation of compounds of formula (I).
The compounds of formulae (II) and (IV) are known, for example as intermediates for the preparation of pesticides, or they can be prepared using processes known perse.
Preparation Examples
A) Preparation of 2-chloro-5-chloromethvl-thiazole
Example P1: 10 g of SO2 are introduced at 20°C into a solution of 73 g of 2-chloro-3-isothiocyanato-1-propene in 133 g of chlorobenzene. Then, over the course of 6 hours, 45 g

of chlorine are introduced under the surface. The reaction mixture is then heated to 50°C, which is maintained until the evolution of gas ceases. There are obtained 232 g of a solution which, according to gas chromatographic analysis, contains 29.4 % 2-chloro-5-chloromethyl-tlhiazole by weight. Yield: 81.3 % of theory, based on 2-chloro-3-isothiocyanato-1-propene.
Example P2: In an analogous experiment, 49 g of chlorine are used without the catalyst, the other amounts of chemicals used and the reaction parameters being left the same as in Example 1. There are obtained 236 g of a solution which, according to gas chromatographic analysis, contains 20.9 % 2-chloro-5-chloromethyl-thiazole by weight. Yield: 58.5% of theory, based on 2-chloro-3-isothiocyanato-1-propene.
Example P3: 35 g of SO2 are introduced, at 30°C, into a solution of 509 g of 2-chloro-3-isothiocyanato-1-propene in 931 g of chlorobenzene. Then, over the course of 6 hours, 290 g of chlorine are introduced under the surface. The reaction mixture is heated to 50'C and is then stirred until the evolution of gas ceases. A vacuum of 120 mbar is then applied and maintained for one hour. By that means there are obtained 1589 g of a solution which, according to gas chromatographic analysis, contains 30.8 % of 2-chloro-5-chloromethyl-thiazole by weight. Yield: 83.2 % of theory, based on 2-chloro-3-isothiocyanato-1-propene.
Distillation of 1571 g of the resulting crude solution at 75°C and an internal pressure of 5 mbar yields 488.2 g of a material which contains 94.5 % 2-chloro-5-chloromethyl-thiazole by weight.
Example P4: 21 g of SO2CI2 are introduced, at 20°C, into a solution of 146 g of 2-chloro-3-isothiocyanato-1-propene in 266 g of chlorobenzene. Then, at 40°C, 69 g of chlorine are introduced under the surface over the course of 5 hours. The reaction mixture is heated to 50°C and is then stirred until the evolution of gas ceases. A vacuum of 120 mbar is then applied and maintained for one hour. There are obtained 441 g of a solution which, according to gas chromatographic analysis, contains 31.2 % 2-chloro-5-chloromethyl-thiazole by weight. Yield: 81.9 % of theory, based on 2-chloro-3-isothiocyanato-1-propene.
Example P5: At 20°C, 11 g of SO2 and then, over the course of 6 hours, 82 g of chlorine are introduced under the surface into a solution of 146 g of 2"Chloro-3-isothio-cyanato-1-propene in 266 g of acetonitrile. The reaction mixture is heated to 50°C and is then stirred until the evolution of gas ceases. A vacuum of 580 mbar is applied and maintained for one hour. By that means there are obtained 467 g of a solution which, according to gas chromatographic analysis, contains 32.7 % 2-chIorO"5"Chloromethyl-thiazole by weight. Yield: 90.8 % of theory, based on 2-chloro-3-isothiocyanato-1-propene.

Example P6: (continuous reaction procedure) At from 20°C to 22°C, 925 g of a solution containing 33 % (by weight) 2-chloro-3-isothiocyanato-1-propene in acetonitrile, 177.5 g of chlorine and 24.7 g of SO2 are continuously and simultaneously introduced, per hour, into a loop reactor having a volume of 370 ml. The reaction mixture flows over into an after-reactor having an internal temperature of 50°C. Each hour there are obtained from the after-reactor 1086 g of a reaction solution containing 32.2 % 2-chloro-5-chloromethy!-thiazole by weight, which corresponds to a yield of 91.1 % of theory, based on 2-chloro-3-isothiocyanato-1-propene.
B) Preparation of 3-(2-chloro-thiazol-5-vl-methvl)-5-methvl-4-nitroimino-perhvdro-1,3,5-oyadiazine
Example P7: 184 g of 3-methyl-4-nitroimino-perhydro-1,3,5-oxadiazine 100 % are introduced into 400 g of dimethyl carbonate in a sulfonation flask, and 168 g of 2-chloro-5-chloromethyl-thiazole 100% are added. The mixture is heated to 65'C. While stirring at from 62 to 68°C, a mixture consisting of 350 g of dimethyl carbonate, 4 g of tetramethyl-ammonium hydroxide pentahydrate and 242 g of potassium carbonate powder is metered in over the course of 60 minutes, thorough stirring of the reaction mixture being maintained until more than 99 % of the 2-chloro-5-chloromethylthiazole has been converted.
The reaction mixture is then cooled and 600 g of water are added. The pH is adjusted to 6.5 using about 260 g of 32 % hydrochloric acid; the mixture is left to stand until the phases have separated, and the organic phase is separated off. The organic phase is concentrated at 60°C in vacuo to a final weight of 600 g. The mixture is slowly cooled to 0-5°C, which is maintained for one hour. The resulting suspension is then filtered.
218 g of the title product having a purity of from 98 to 99 % (74 % of theory, based on 2-chloro-5-chloromethylthiazole 100 %) are obtained.
The invention relates also
(B) to a process for the preparation of a compound of formula (I) as defined hereinbefore under (A), wherein
c) a compound of formula (II) as defined hereinbefore under (A) is reacted with a chlorinating agent to form a compound of formula

or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and
d) the compound of formula (111) thereby obtained is reacted with a compound of formula (IV) as defined hereinbefore under (A);
in which process the compound of formula (III) is subjected to intermediate purification in a melt crystallisation process;
to a process for the preparation of a compound of formula (111) according to process c) hereinbefore, and to the use of the compounds of formulae (II), (III) and (IV) in a process as described hereinbefore.
The compounds of formula (1) are known as valuable pesticides, and synthesis nhethods for those compounds are described in the literature. It has, however, been found that especially the compound of formula (III) prepared according to the processes known from the literature does not satisfy the requirements in terms of purity, that it is - probably because of those impurities - thermally unstable, which can in turn lead to significant safety problems in a production plant, and also that the known processes have significant disadvantages in respect of further parameters, for example yield and quality of the end products of formula (1) above, and the like.
The known preparation processes are therefore not satisfactory in every respect, which is why there is a need to provide improved preparation processes for the compounds of formula (I) and especially of formula (111). It has now been found that the compound of formula (111) can, using the purification process claimed according to the invention, be prepared, for example, with higher purity and that working with and storing the compound 2-chloro-5"Chloromethylthia2ole are associated with a significantly reduced safety R1sk compared to the processes known from the literature.
Purification by melt crystallisation of 2-chloro-5-chloromethylthiazole has several advantages over other purification methods. Because 2-chloro-5-chloromethylthiazole is thermally unstable and, in addition, has a "thermal memory", which means that the compound becomes more unstable with increasing thermal stress, any kind of thermal stress Should be avoided as far as possible. Moreover, in the case of distillative purification, for example, it is not readily possible for all subsidiary products to be separated. Distillative purification requires columns having high numbers of plates, which requires a higher

distillation temperature, combined with the correspondingly greater loss of product and reduced thermal safety of the distillation process.
Melt crystallisation normally yields at least 98 % pure 2-chloro-5-chloromethylthiazole. It is also possible for the mother liquor to be recycled in order to recover the 2-chloro-5-chloromethylthiazole present therein. Melt crystallisation moreover offers the advantage that the R1sk of corrosion to the apparatus is minimised because of the low working temperatures and, furthermore, that neither solvents nor other additives are employed in the process.
Preference is given within the scope of the invention (B) to a process for the preparation of a compound of formula (I)
(1) wherein R1 and Rg in the compounds of formulae (I) and (IV) together are -CH2-O-CH2-, -CH2-CH2-CH2- or -CH2-CH2-;
(2) wherein Q is N;
(3) wherein Y is NO2;
(4) wherein Z is NR3 and R3 is H or C1-C4alkyl;
(5) wherein the purification step is carried out in process step a) at from CC to +25°C, especially at from +5°C to H-15C; ,
(6) wherein X in the compound of formula (II) is halogen such as fluorine, chlorine or bromine; especially chlorine or bromine, more especially wherein X is chlorine;
K
(7) wherein, in process step c), there is used an aprotic polar solvent having a dielectric constant greater than 10; especially greater than 20; more especially greater than 25; very especially greater than 30;
(8) wherein, in process step c), there is used as solvent a carboxylic acid nitrile, e.g. acetonitrile, propionitrile or butyronitrile; a carboxylic acid amide, e.g. formamide, N-methyl-formamide, N,N-dimethylformamide, N-methylacetamide, N,N-dimethylacetamide or 1-methylpyrrolidin-2-one; a carbonic acid ester, e.g. propylene carbonate; a nitroalkane, e.g. nitromethane or nitroethane; nitrobenzene; a sulfoxide, e.g. dimethylsulfoxide; sulfolane; hexamethylphosphoric acid triamide; 1,3-dimethylimidazolidin-2-one; a urea derivative, e.g. tetramethylurea; or an ether, e.g. dioxane, tetrahydrofuran. ethylene glycol dimethyl ether or dimethoxydiethyl ether; or mixtures of such solvents;

(9) wherein as halogenating agent there is used Cl2, a mixture of CI2 and SO2 or a
niixture of CI2 and S02Cl2; especially wherein chlorination is performed using CI2, and SO2 or
SO2CI2 is used in catalytic amounts, more especially wherein SO2 or SO2CI2 is used in an
amount of from 10 to 40 mol %, based on the starting material of formula (II);
(10) wherein in process step c) a continuous procedure is employed for the preparation
of the crude compound of formula (III).
The process is especially suitable for the preparation of thiamethoxam, known from WO 98/32747; and of Ti-435 (clothianidin), known from EP-A-446 913.
The dielectric constants of suitable solvents can be found, for example, in C. Reichardt, Solvents and Solvent Effects, VCH Verlagsgesellschaft, Weinheim, 1988, Table A-1, pages 408 to 410. The temperatures at which those values apply can also be found in the said table.
Othenwise, the conditions applying to process steps c) and d) are the same as those set out under invention statement (A) for process steps a) and b).
Salts of compounds of formulae (I) to (IV) can be prepared in a manner known perse as mentioned hereinbefore under invention statement (A).
Salts of compounds of formulae (I) to (IV) can also be converted into the free compounds of formulae (I) to (IV) in conventional manner as mentioned hereinbefore under invention statement (A).
Salts of compounds of formulae (I) to (IV) can be converted into different salts of compounds of formulae (I) to (IV) in a manner known perse.
The compounds of formulae (I) to (IV), and salts thereof, may also be obtained in the form of hydrates and/or may include other solvents, for example solvents that may optionally have been used for the crystallisation of compounds that occur in solid form.
The invention relates to all those embodiments of the process according to which a compound obtainable as starting material or intermediate at any stage of the process is used as starting material and all or some of the remaining steps are carried out, or in which a starting material is used in the form of a derivative or a salt and/or its racemates or antipodes, or, especially, is formed under the reaction conditions.

Compounds of formulae (I), (III) and (IV) obtainable in accordance with the process or by other means can be converted into different corresponding compounds in a manner Known perse.
In the process of the present invention there are preferably used those starting materials and intermediates, in each case in free form or in salt form, which result in the compounds of formula (I) or salts thereof described at the beginning as being especially valuable.
The present invention relates also to a melt crystallisation process for purification of a compound of formula (III).
An especially preferred aspect of the invention is a continuous purification process for the compound of formula (III), for example by means of a fluid bed which has a temperature gradient.
The invention relates especially to the preparation processes described in the Examples.
The preferences applying to the substituents of compounds of formula (IV) are the same those mentioned hereinbefore in the processes for the preparation of compounds of formula (I).
The compounds of formulae (II) and (IV) are known, for example as intermediates for the preparation of pesticides, or they can be prepared using processes known perse.
Preparation Examples
Example P8: At 20°C, 143.2 g of sulfuryl chloride are metered into a solution of 147.5 g of 2-chloro-3HSOthiocyanato-1-propene in 150 g of acetonitrile over the course of about 2 hours. The reaction is slightly exothermic. Towards the end of the reaction, the solution is heated to 40°C and is maintained at that temperature for one hour, during which marked evolution of gas can be observed. The solvent, together with the hydrochloric acid, is concentrated in vacuo. 187.0 g of a 77 % solution of 2-chloro-5-chloromethyl-thiazole are obtained, which corresponds to a yield of 86 % of theory, based on 2-chloro-3-isothio-cyanato-1 -propene.
Example P9: At 20°C, 67.5 g of 2-chloro-3-isothiocyanato-1 -propene are introduced into 75 ml of dimethylformamide, and 6.8 g of sulfuryl chloride (0.05 mol) are added to the neaction mixture. 32.5 g of chlorine are then introduced over the course of about 2 hours until

an excess of starting material can no longer be detected. After the addition is complete, the reaction solution is heated to SOX and maintained at that temperature for one hour. Finally, the HCI formed and the solvent are drawn off in vacuo. 2-Chloro-5-chloromethyl-thia2ole having a content of 72 % is obtained.
Example P10: At 20X, 87.7 g of 2-chloro-3-isothiocyanato-1-propene are introduced into 100 ml of nitromethane. 41.5 g of chlorine are then introduced over the course of about 2 hours until an excess of starting material can no longer be detected. The reaction solution is then stirred at 40°C for one hour and is cooled again. The HCI is drawn off in vacuo and the nitromethane is distilled off. 2-Chloro-5-chloromethyl-thiazole having a content of 91 % is obtained. The product contains approximately 1 % of the subsidiary product of formula

Example P11: 166.6 g of 2-chloro-3-isothiocyanato-propene are introduced into 300 g of 1,2-dichloroethane in a double-walled reactor. At 30°C, 78 g of chlorine are introduced over the course of 4-5 hours. The reaction mixture is then heated to 60°C, which is maintained for 60 minutes until the evolution of gas (HCI) has ceased. The reaction mixture is then cooled to room temperature and 200 g of 37 % hydrochloric acid are added, with stirring. After the phases have separated, the organic phase is extracted a further four times using 100 g of 37 % hydrochloric acid each time. The aqueous extracts, which contain the product, are combined, 800 g of water are added and extraction using five portions of 1,2-dichloroethane totalling 500 g is carried out. The extracts are combined and the solvent is evaporated off. A crude melt having a content of about 92 % is obtained.
Example PI 2: 2,5 kg of liquid 2-chloro-5-chloromethyI-thiazole having a content of 95 % are cooled to 10°C in a glass beaker, provided with a seed crystal and left to stand at 10°C for 5 hours. A two-phase mixture having a brown, liquid, upper phase and a crystalline lower phase is formed. The liquid phase is separated off and the solid phase is transferred to a filter and allowed to drain for one hour. 2.3 kg of the title product are obtained in the form of white needles having a content of more than 99 % and a melting point of from 28°C to 29°C.

Example P13: 3-(2-ChlorQ-thiazol-5-vl-methvl)-5-methvl-4-nitroimino-perhvdro-1,3,5-Qxadiazine: 184 g of 3-methyI-4-nitroimino-perhydro-1,3,5-oxadiazine 100 % are introduced irito 400 g of dimethyl carbonate in a sulfonation flask and 170 g of 2-chloro-5-chloro-methylthiazole having a content of 99 % are added. The mixture is heated to 65°C. While stirring at from 62°C to 68°C. a mixture consisting of 350 g of dimethyl carbonate, 4 g of tetramethylammonium hydroxide pentahydrate and 242 g of potassium carbonate powder are metered in over the course of 60 minutes, thorough stirring of the reaction mixture being maintained until more than 99 % of the 2-chloro-5-chloromethylthiazole have been converted (monitored by LC).
The reaction mixture is then cooled and 600 g of water are added. The pH is adjusted to 6,5 using about 260 g of 32 % hydrochloric acid; the mixture is left to stand until the pjhases have separated, and the organic phase is separated off. The organic phase is concentrated at 60°C in vacuo to a final weight of 600 g. The mixture is slowly cooled to 0-5°C, which is maintained for one hour. The resulting suspension is then filtered.
218 g of title product having a purity of from 98 to 99 % (74 % of theory, based on 2-chloro-5-chloromethylthiazole 100 %) are obtained.

WE CLAIM:
1. A process for the preparation of a compound of formula

and, where appropriate, an E/Z isomer, a mixture of E/Z isomers and/or a tautomer
thereof, in each case in free form or in salt form, wherein
Q is CH or N;
Y is NO2 OR CN;
Z is CHR3, O, NR3 or S;
Ri and R2 either are each independently of the other hydrogen or CpCgalkyl which is unsubstituted or substituted by R4 or together are an alkylene bridge having two or three carbon atoms which optionally contains a hetero atom selected from the group consisting of NR5, O and S,
R3 is H or C1-C12alkyl which is unsubstituted or substituted by R4,
R4 is unsubstituted or substituted aryl or heteroaryl, and
R5 is H or C1-C12alkyl; wherein a) a compound of formula
wherein X is a leaving group, is reacted with a chlorinating agent at a temperature of 0°C to 50°C using chlorine, POCI3, PCI3, PCI5 or SO2CI2 or a mixture of chlorine and SO2CI2 as chlorinating agent to form a compound of formula

or, where appropriate, a tautomer thereof, in each case in free form or in salt form; and b) the compound of formula (III) thereby obtained is reacted at a temperature of 10°C to 80°C in the presence of a base with a compound of formula

wherein Ri, R2, Y, Z and Q are as defined hereinbefore for the compound of formula
(I);
in which process the chlorination according to process step a) is performed using a chlorinating agent in the presence of a catalytic amount of SO2.
2. The process as claimed in claim 1, wherein the process step a) is carried out in acetonitrile.
3. The process according to any one of claims 1 or 2, wherein in process step a) SO2 is used in an amount of from 1 mol % to 50 mol %, based on the starting material of formula (II).
4. The process for the preparation of a compound of formula

wherein a compound of formula

wherein X is a leaving group, or, where appropriate, a tautomer thereof, in each case
in free form or in salt form, is reacted with a chlorinating agent;
in which process the chlorination is performed in the presence of a catalytic amount of
SO2.
5. The process for the preparation of a compound of formula (I) as claimed in claim 1, wherein the intermediate compound of formula (III) is purified by melt crystallization.

Documents:

289-chenp-2003-abstract.pdf

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289-chenp-2003-correspondnece-others.pdf

289-chenp-2003-correspondnece-po.pdf

289-chenp-2003-description(complete) duplicate.pdf

289-chenp-2003-description(complete) original.pdf

289-chenp-2003-form 1.pdf

289-chenp-2003-form 18.pdf

289-chenp-2003-form 26.pdf

289-chenp-2003-form 3.pdf

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Patent Number

209616

Indian Patent Application Number

289/CHENP/2003

PG Journal Number

50/2007

Publication Date

14-Dec-2007

Grant Date

05-Sep-2007

Date of Filing

18-Feb-2003

Name of Patentee

M/S. SYNGENTA PARTICIPATIONS AG

Applicant Address

Schwarzwaldallee 215, CH-4058 Basel

Inventors:

#	Inventor's Name	Inventor's Address
1	DESPONDS Olivier	Syngenta Crop Protection Monthey SA, Route de l'Ile au Bois, CH-1870 Monthey
2	FABER Dominik	Syngenta Crop Protection Schweizerhalle AG, Rothausweg, CH-4133 Schweizerhalle
3	GRESSLY Remy	Syngenta Crop Protection Monthey SA, Route de l'Ile au Bois, CH-1870 Monthey
4	RAPOLD Thomas	Syngenta Crop Protection Munchwilen AG, Im Breitenloh 5, CH-4333 Munchwilen
5	PASSAFARO Marco	Quellenstrasse 11, 8200 Schaffhausen, CH-4133 Schweizerhalle

PCT International Classification Number

C07D 277/32

PCT International Application Number

PCT/EP2001/009663

PCT International Filing date

2001-08-21

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	1653/00	2000-08-23	Switzerland
2	1651/00	2000-08-23	Switzerland