MXPA06005193A - Cis-trans isomerisation of semicarbazone compounds - Google Patents

Abstract

The present invention relates to the isomerisation of the Z-isomer I-Z of semicarbazone compounds of the general formula (I) into its E-isomer I-E, where the variables in formula (I) have meanings given in claim 1.

Description

ISOMERIZATION C S-TRANS OF SEMICARBAZONE COMPOUNDS BACKGROUND OF THE INVENTION The present invention relates to the isomerization of the I-Z of the Z isomer of the semicarbazone compounds of the general formula I within its I-E of the E-isomer wherein the variables in formula I have the following meanings: m, p and q are each independently an integer of 0, 1, 2, 3 or 4 R1, R2, R3 are each independently halogen; OH; CN; N02; C3-C3 alkyl, optionally substituted with C! -C alkoxy, C? -C4 haloalkoxy or C3-C3 cycloalkyl; haloalkyl of C? -C6; C3-C3 cycloalkyl; Ca-Ce alkoxy, optionally substituted with C 1 -C 4 alkoxy or C 3 -C 6 cycloalkyl; haloalkoxy of C? -C3; C? -C6 alkylcarbonyl; C3 ~ CS cycloalkoxy; C 4 -C 6 alkoxycarbonyl or C 6 -C 6 alkoxycarbonyloxy. The semicarbazone compounds of the general formula I are known from EP-A-462456 to be effective as "pest controlling agents." The semicarbazones of the formula I have two geometric isomers with respect to the double bond C = N, that is, the EI of form E and the IZ of form Z.

At room temperature, these geometric isomers are stable with respect to the E / Z isomerization. Regarding the relative pesticidal activity of these compounds, EI of form E is generally more active than IZ of form Z. Therefore, the agricultural and commercially acceptable specifications of semicarbazones I require an E / Z ratio of at least 9: 1 and preferably at least 10: 1. The compounds of the formula I can be prepared by the process illustrated in the following scheme: Significant amounts of the I-Z of the unwanted Z-isomer are formed by this process. In addition, much effort is needed to achieve the desired E / Z ratio. First, extensive reaction times are required to achieve a high E / Z ratio in the hydrazone precursor II, necessary to obtain the desired E / Z ratio in the final product I. Secondly, the crystallization of the I-Z from the Z isomer in the presence of I-Z of the Z-isomer is tedious and difficult. In order to obtain a high isolated yield of the desired E-isomer, some of the Z-isomer must also be crystallized with the E-isomer from the reaction mixture. Similarly, in order to obtain the desired E / Z ratio in the crystallized product, a low isolated efficiency of the E-isomer is necessary, so that the undesired Z-isomer is completely solubilized together with the significant amount of the E-isomer in the reaction mixture. Third, the recrystallization of the isolated product I containing significant amounts of the unscathed Z-isomer to obtain the desired E / Z ratio is also tedious and difficult. As with the crystallization from the reaction mixture, both the low crystallization reactivations and the content of the high Z isomer of the final product are obtained. These involve the risk of isolating either a low yield product or having no required E / Z ratio. Consequently, there is a need for a method which allows a simple isomerization of the Z isomer of I within its I-E of the E-isomer.

SUMMARY OF THE INVENTION The present invention has surprisingly found that the Z-isomer of compound I can be isomerized within the E isomer of I by reacting the I-Z of Z form or a mixture of I-E and I-Z of the geometric isomers in the presence of iodine. This result was quite surprising since the irradiation of the IZ and IE mixtures of the geometric isomers leads predominantly to the IZ of the Z isomer. Therefore, the present invention relates to a process for the isomerization of the IZ of the Z-isomer of a compound of the general formula I as defined above within its EI of the E isomer by reacting the IZ of the Z isomer or a mixture of the IZ and IE of the geometric isomers in the presence of iodine.

DETAILED DESCRIPTION OF THE INVENTION In general, approximately 0.1% by weight, preferably at least 0.2% by weight and more preferably at least 0.5% by weight of iodine, based on the total amount of compound I, are required to achieve isomerization within acceptable reaction times. For practical reasons, the amount of iodine will not exceed 10% by weight and preferably not exceed 5% by weight, based on the total amount of compound I. More preferably, isomerization is carried out in the presence of 1 to 4 % by weight of iodine. In general, the reaction temperature will be at least 40 ° C, preferably at least 50 ° C and more preferably at least 60 ° C to achieve isomerization within an acceptable reaction time. For practical reasons, the reaction temperature will generally not exceed 150 ° C and preferably not exceed 100 ° C. The process of the invention can be carried out starting from the IZ of the almost pure Z-isomer (E / Z ratio <5:95) or from mixtures of the EI and IZ of the geometric isomers (E / Z ratio> 5:95). ). In a preferred embodiment of the present invention a mixture of the EI and IZ of the geometric isomers having an E / Z ratio varying from 1: 1 to 15: 1, preferably from 2: 1 to 15: 1 and especially from 3 : 1 to 10: 1 is used as a starting material. In general, the isomerization of I is carried out until an E / Z ratio of at least 95: 5, preferably at least 97: 3 and more preferably at least 98: 2 is reached. The reaction time which is required to achieve the desired E / Z ratio is in the range from 20 minutes to 14 hours, preferably 1 to 8 hours and more preferably 2 to 4 hours. The isomerization can be carried out in an inert organic solvent or diluent. Suitable solvents are aromatic solvents such as benzene, toluene, xylenes, chlorobenzene, dichlorobenzene, acyclic ethers such as diethyl ether, methyl tert-butyl ether, alicyclic ethers such as tetrahydrofuran and dioxane, alkanes such as methanol, ethanol, propanol, isopropanol, n-butanol, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile and propionitrile, carbonates such as dimethylcarbonate, diethylcarbonate, ethylene carbonate and propylene carbonate, aliphatic and alicyclic hydrocarbons such as hexane, isohexane, heptane and cyclohexane and mixtures of the aforementioned solvents. Preferred solvents are the aforementioned aromatic solvents especially toluene, xylene and mixtures of the aforementioned solvents, which contain at least 50% by volume of the aforementioned aromatic solvents. In order to perform the isomerization in an inert solvent or diluent, the IZ of the Z isomer or a mixture of the IE and IZ of the geometric isomers can be dissolved or suspended in a suitable solvent and reacted in the presence of iodine as described previously. It is also possible to carry out the isomerization either in the reaction mixture obtained from the reaction of the hydrazone II and the isocyanate III or in the mother liquor obtained after the crystallization of the compound I from the reaction mixture. In order to obtain the I-E of the E-isomer, optionally together with small amounts of the Z-isomer Z-Z, the εomerization mixture is developed in a usual manner. Preferably, I-E of the isomer, optionally together with small amounts of I-Z of the isomer (generally not more than 5% by weight) is isolated from the liquid reaction mixture by crystallization or precipitation. Crystallization or precipitation can be achieved either by cooling and / or concentration of the liquid reaction mixture and / or by the addition of an inert solvent which decreases the solubility of compound I in the reaction mixture. Suitable solvents for decreasing the solubility of compound I are aliphatic or alicyclic hydrocarbons such as hexane, heptane, isohexane and cyclohexane. In another preferred embodiment of the present invention, the isomerization of I-Z is carried out in the absence of a solvent or diluent. In other words, the isomerization of the I-Z of the Z isomer is carried out in the solid phase or in the molten phase. In this way, the solid or molten I-Z compound or a solid or molten mixture of the I-E and I-Z of the geometric isomers is reacted with iodine as described above. After the desired degree of isomerization is achieved, the iodine can be removed simply by sublimation, for example, by increasing the temperature and / or applying reduced pressure. The residue usually contains only compound I having an increased E / Z ratio with respect to the starting material and optionally those impurities contained in the starting material. The residue does not usually contain any additional impurities. The starting materials for isomerization in the absence of a solvent or diluent can be the pure Z-isomer or mixtures of the I-E and I-Z of the geometric isomers. Examples of such mixtures are crystalline products which do not meet the required E / Z ratio and the residue obtained from the mother liquor of the crystallization of I during the development in the preparation of I.

The organic portions mentioned in the above definitions of the variables are - like the term halogen - the collective terms for the individual lists of the members of the individual group. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group. The term halogen in each case denotes fluorine, bromine, chlorine or iodine, in particular fluorine or chlorine. Examples of other meanings are: The term "C?-C6 alkyl" as used herein and the C porciones-C6 alkoxy alkyl, C?-C6 alkoxycarbonyl, C - alkylcarbonyl and alkoxycarbonyloxy C? -C6 refers to a straight or branched chain, saturated hydrocarbon group having from 1 to 6 carbon atoms, especially from 1 to 4 carbon groups, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1-2. dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl. Alkyl of C? -C4 means, for example, methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl or 1,1-dimethylethyl. In the alkyl of Ca-C3, a hydrogen can be substituted by a radical, selected from C 1 -C 4 alkoxy, C 2 -C 4 haloalkoxy and C 3 -C 3 cycloalkyl. The term "C6-C6haloalkyl" as used herein refers to a saturated, straight or branched chain alkyl group having 1 to 6 carbon atoms (as mentioned above), wherein some or all of the hydrogen atoms in these groups can be replaced by halogen atoms as mentioned above, for example, haloalkyl of C! -C, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, chloroethyl, 1-bromoethyl, 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, pentafluoroethyl and the like. The term "C 1 -C 2" -fluoroalkyl as used herein, refers to a C 1 -C 2 alkyl which carries 1, 2, 3, 4 or 5 fluorine atoms, for example, difluoromethyl, trifluoromethyl, fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl or pentafluoroethyl The term "Cx-Cg alkoxy" as used herein and alkoxy portions of Cx-Cg alkoxycarbonyl and C6-C6 alkoxycarbonyloxy refers to a straight or branched chain saturated alkyl group having 1 to 6 carbon atoms (as mentioned above) which is attached through an atom Oxygen to the rest of the molecule Examples include methoxy, ethoxy, OCH2-C2H5, OCH (CH3) 2, n-butoxy, OCH (CH3) -C2H5, OCH2-CH (CH3) 2, OC (CH3) 3, n-pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1,1-dimethylpropoxy, 1, 2-dimethylpropoxy, 2, 2-dimethyl-propoxy, 1-ethylpropoxy, n-hexoxy, 1-methylpentoxy, 2- methylpentoxy, 3-methylpentoxy, 4-methylpent oxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1, 1 2-trimethylpropoxy, 1, 2, 2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, 1-ethyl-2-methylpropoxy and the like. In the C-C6 alkoxy, a hydrogen can be substituted by a radical, selected from the C-C6 alkoxy and the C3-C6 cycloalkyl. The term "C6-C6 haloalkoxy" as used herein refers to a C6-C6 alkoxy group as mentioned above which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, ie, for example, haloalkoxy of C? -Ce such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, -bromoethoxy, 2-iodoethoxy, 2, 2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, , 2,2-trichloroethoxy, pentafluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy, 2, 2-difluoropropoxy, 2,3-difluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 2-bromopropoxy, 3-bromopropoxy , 3, 3, 3-trifluoropropoxy, 3,3,3-trichloropropoxy, 2,2,3,3,3-pentafluoropropoxy, heptafluoropropoxy, 1- (fluoromethyl) -2-fluoroethoxy, 1- (chloromethyl) -2-chloroethoxy , 1- (bromomethyl) -2-bromoethoxy, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, nonafluorobutoxy, -fluoro-1-pentoxy, 5-chloro-l-pentoxy, 5-bromo-l-pentoxy, 5-iodo-1-pentoxy, 5,5,5-trichloro-l-pentoxy, undecafluoropentoxy, 6-fluoro- 1-hexoxy, 6-chloro-1-hexoxy, 6-bromo-1-hexoxy, 6-iodo-1-hexoxy, 6,6-trichloro-1-hexoxy or dodecafluorohexoxy, in particular chloro ethoxy, fluoromethoxy, difluoromethoxy , trifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trifluoroethoxy. The term "C3-C6 cycloalkyl" as used herein refers to a cycloaliphatic radical having from 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The cycloalkyl radical can be unsubstituted or can carry 1 to 6 C? -C6 alkyl radical, preferably a methyl radical.

In general, isomerization can be carried out in any of the compounds of the formula I. In a preferred embodiment of the invention, the variables m, p and q are each 1. Preferred radicals R.sup.1, R.sup.2, R.sup.3 are each independently halogen, CN, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 haloalkyl, alkoxy C? -C3 or C? -C6 haloalkoxy. More preferably, R1 is halogen or haloalkyl of C? -C4, especially CF3, R2 is CN and R3 is haloalkoxy of C? -C4, especially OCF3. An example of an especially preferred compound I is a compound wherein R1 is CF3 located at the 3-position of the phenyl ring, R2 is CN located at the 4-position of the phenyl ring and R3 is 0CF3 located at the 4-position of the phenyl ring. This compound is referred to as 1.1, the isomers are referred to as I.l-E and I.l-Z. ++++ 7a The process of the present invention allows easy isomerization of the ZZ isomer within its IE of the E isomer. The isomerization usually produces a high E / Z ratio which exceeds 95: 5, preferably 97: 3 and more preferred 98: 2. No significant amounts of byproducts are formed, ie the yield of compound I is > 99% Therefore, the process of the present invention can be used to simplify the preparation of compounds I with the desired E / Z ratio of = 9: 1. The following examples are intended to illustrate the present invention without limiting its scope.

Example 1: Conversion of the pure Z form of compound I .1 into its E form. A mixture of 2 g of I.l-Z of the Z isomer and 0.04 g of the iodine was heated to 90 ° C in a sealed tube. Liquid chromatography (see below) shows that the product contains 97.8% of I.l-E of the E-isomer and 2.2% of the I.l-Z of the Z-isomer (ratio E / Z 97.8: 2.2). The iodine was then stirred in vacuo at 90 ° C for two hours. The recovery performance was 100%. No other impurities could be detected by liquid chromatography. Liquid chromatography: column: reversed phase RP 8 column, romasil 100-3.5C8; element: acetonitrile / gradient (water + 0.1% trifluoroacetic acid, pH 2.4); Detection: UV 2235.4 nm.

Example 2: Treatment of an unpurified reaction mixture containing 97.3% of compound 1.1 having an E / Z ratio of about 4.9: 1. Two grams of a solid containing approximately 97.3% of compound 1.1 having an E / Z ratio of about 4.9: 1 and 0.04 g of iodine was heated at 90 ° C in a sealed tube for two hours. The iodine was then stirred in vacuo, drying at 90 ° C overnight. The recovery performance is approximately 100%. No additional impurities could be detected. The product contained 95.9% by weight of I.l-E of the E-isomer and 1.4% by weight of I.l-Z of the Z-isomer as determined by liquid chromatography (E / Z ratio 68.5: 1).

Example 3: Conversion of the Z form of the compound I .1. 8 g of chlorobenzene were suspended in 2 g of compound I.l-Z and 0.1 g of iodine and the resulting suspension was heated at 60 ° C for six hours. Then, the reaction mixture was cooled and 10 g of hexanes were added. The reaction product was filtered and dried in an oven at 70 ° C overnight. In this way, 1.8 g were obtained. So an E / Z ratio of approximately 12: 1 was achieved.

Claims (8)

CLAIMS 1. A process for the isomerization of the I-Z of the Z-isomer of a compound of the general formula I within its I-E of the E-isomer
1. (1.1-E) (1.1-Z) wherein m, p and q are each independently an integer of 0, 1, 2, 3 or 4 R1, R2, R3 are each independently halogen; OH; CN; N02; C? -C6 alkyl, optionally substituted with C4C4 alkoxy, C? -C4 haloalkoxy or C3-C6 cycloalkyl; haloalkyl of C? -C6; C3-C6 cycloalkyl; C? -C6 alkoxy, optionally substituted with C? -C4 alkoxy or C3-C3 cycloalkyl; haloalkoxy of C? -C3; C? -C6 alkylcarbonyl; C3-C6 cycloalkoxy; C6C6 alkoxycarbonyl or C6C6 alkoxycarbonyloxy; which is characterized in that the I-Z of the Z isomer or a mixture of the stereoisomers 1-Z and I-E are reacted in the presence of iodine.
2. 2. The process as claimed in the claim 1, wherein iodine is used in amounts from 0.1 to 10% by weight, based on the total amount of the compound of the general formula I.
3. 3. The process as claimed in claim 1, wherein the isomerization is carried out in an inert solvent or diluent.
4. 4. The process as claimed in claim 1, wherein the isomerization is performed in the absence of a solvent or diluent.
5. 5. The process as claimed in the claim 1, wherein a mixture of the I-Z and I-E of the isomers having an E / Z ratio ranging from 15: 1 to 2: 1 are reacted.
6. 6. The process as claimed in claim 1, wherein the isomerization is carried out at a temperature ranging from 40 to 150 ° C.
7. 7. The process as claimed in claim 1, wherein in the formula I m, p and q are each 1 and R1, R2, R3 are each independently halogen, CN, C? -C3 alkyl, haloalkyl of C? -C6, C-C6 alkoxy or C? -C6 haloalkoxy.
8. 8. The process as claimed in claim 7, wherein in formula I, R1 is CF3 located in the 3-position of the phenyl ring, R2 is CN located in the 4-position of the phenyl ring and R3 is OCF3 located in the position 4 of the phenyl ring.