The method of obtaining the lambda-cyhalothrin isomerization
(57) Abstract:Describes how to obtain the lambda-cyhalothrin in the form of a racemic modification, containing S--cyano-3-phenoxybenzyl-1R, 3R-3-(Z-2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylate and its enantiomer, including the processing of cyhalothrin in the form of a mixture of four isomers in approximately equal amounts, which contains two isomers, the components of the lambda cigalotrin and epimer of these two isomers in solution or in suspension in isopropanol, wherein the treatment is carried out in the wet isopropanol, containing 2 to about 15. % of water, sodium cyanide, taken in an amount of 0.5 to 15.0 mol. % the number of cyhalothrin, at a temperature of -10o- +20o. The technical result is simplification. 3 C.p. f-crystals, 1 table. The invention relates to a method for converting a first isomer to the second isomer, in which the first and second isomers are epimerase the same connection.Pyrethroids are usually obtained by means of esterification, which give a mixture of isomers. It is known that some isomers have a greater insecticidal effect than others, and this has led to the development of methods to separate the more active isomers and probe N 1582594, European patent N 107296 and U.S. patent N 4997970, and they all differ in the use of reason. However these methods are the basis not only contributes to the desired isomerization by removal of a proton, leading to the epimerization at the carbon atom that carries a cyano group, but also that it is undesirable, can catalyze the decomposition of esters, resulting in a reduced yield of the desired product.A number of these PYRETHROID products containing only one or two isomers were released on the market. It products such as deltamethrin /S--cyano-3-phenoxybenzyl 1R,3R-/2.2-dibromovinyl /-2,2-dimethylcyclopropane carboxylate/, acrinathrin /S--cyano-3-phenoxybenzyl Z-1R,3S-3- [2-/2,2,2-Cryptor-1-cryptanalytically/vinyl] - 2,2-dimethylcyclopropane carboxylate/, S-fenvalerate /S--cyano-3-phenoxybenzyl S-2-/4-chlorophenyl/-3-methylbutyrate/, and lambda cigalotrin/ racemic combination S--cyano-3 - phenoxybenzyl 1R,3R-3-/Z-2-chloro-3,3,3-Cryptocom-1-EN-1-yl/- 2,2-dimethylcyclopropane of carboxylate and its enantiomer/.The closest according to the proposed method is a method of obtaining cyhalothrin in the form of crystalline enantiomeric pairs, including the processing of cyhalothrin in the form of a mixture of four isomers, in approx evritania dried, at the temperature of (-10) - (+5)oC, with the addition of crystals of the enantiomeric pair of isomers (see 1225483 A).According to the present invention proposes a method of obtaining a lambda of cyhalothrin in the form of a racemic modification, containing S--cyano-3-phenoxybenzyl 1R, 3R-3-(Z-2-chloro-3,3,3-Cryptocom-1-EN-1-yl) -2,2-dimethylcyclopropane carboxylate and its enantiomer, including the processing of cyhalothrin in the form of a mixture of four isomers in approximately equal amounts, which contains two isomers, the components of the lambda cigalotrin and epimer of these two isomers in solution or in suspension in isopropanol, the distinguishing feature of which is the fact that what treatment is carried out in the wet isopropanol containing 2 to 15% vol. water, sodium cyanide, taken in an amount of 0.5 - 15 mol.% the number of cyhalothrin, when the temperature - 10...+20oC.It is preferable to use epimer obtained industrially in a mixture with isomers. While cyanide can be used in solid form or in the form of an aqueous solution in the presence of a catalyst phase transfer
The method of the invention can also be used to obtain deltamethrin, acrinathrin, S-fenvalerate and lambda-cyhalothrin products from PressTV the fear of loss of output due to accelerated basis decomposition. Furthermore, the method reduces the time cycle, indicating that the use of isomerization involving cyanide leads to unexpected significant economic advantage in comparison with known methods of epimerization with the base as a catalyst.The exact mechanism by which the method of the invention leads to isomerization of epimere the desired isomer and the product is not known, but a possible explanation may be the effect on the carbon atom bearing a cyano, a cyanide ion, a defiant move ceanography mechanism SN2 with concomitant inversion of chirality. Since the isomer of the product is less soluble than the epimer, he will yet to crystallize from the reaction mixture as soon as the solution becomes saturated with respect to the isomer, and this leads the process in favor of a less soluble isomer.Polar organic solvents or diluents that can be used for the process of the invention are those in which the isomer product or racemic modification is less soluble than its epimer or the racemate. This can be, for example, monobasic lower alcohols containing up to six carbon atoms, such as isopro is, the AK ethyl acetate, or mixtures with alcohols, to obtain an environment that will allow isomer and epimer be separated on the basis of the difference in solubility. There may be a portion of the water within the Miscibility, but it is usually less than 20% by volume.Preferably the solvent is a branched lower alcohol like isopropanol containing 2 to 15% by volume of water.The source of cyanide ions may be cyanide alkaline or alkaline earth metal, or Quaternary ammonium cyanide. The most preferred sodium cyanide or potassium cyanide. It can be used in solid form, in this case, any residual material at the end of the process must be separated from the solid product by selective solubility, or by washing with water to dissolve the cyanide, or by extraction with an organic solvent to dissolve the product. In another case, the cyanide may be in the form of an aqueous solution, which, when used in excess can enforce two-phase system, where you use certain solvents, in this case, the method is facilitated by use of catalysts phase ammonium. Better if cyanide is present in the amount of 0.5 to 15.0 mol.% in relation to the epimer.One of the suitable methods for the extraction of the product will be uploading the contents of the reactor in excess of diluted acid, such as sulfuric acid, or, better, a dilute water solution of alkali metal hypochlorite. This technique can be used with reaction mixtures with cyanide in solid or dissolved form, and this allows you to regenerate the product by filtration or by extraction of the solvent.The method is carried out in a reactor in which the temperature can be controlled by external heating or cooling. The rate of decomposition of the crystalline product is enhanced by reducing the solubility of the product at lower temperatures and when shaking the contents of the reactor to thoroughly mix.The timing will depend on the speed of formation of the product and it is not desirable that it was less than one hour and more than 60 hours. The exact conditions depend on the specific product. The method is carried out at a temperature in the range -10 to +20oC for 15 to 45 hours.Although for some appropriate temperature for a certain period of time, it is often useful, especially for products with a lower melting temperature or a relatively high solubility, to add a portion of the product in solid crystalline form to the mixture to provide a crystalline surface, which can further crystallize the product. The number of added crystalline product is not critical, provided that it is enough to get a saturated solution with a portion remaining in the undissolved state at a certain operating temperature.For a better understanding of the invention offers the following examples illustrate the use of the method to obtain the lambda-cyhalothrin. As already mentioned, the lambda cigalotrin is a racemic product, consisting of isomer S--cyano-3-phenoxybenzyl 1R,3R-3-/Z-2-chloro-3,3,3-cryptographp-1-EN-1-yl/2,2 - cyclopropanecarboxylate and its enantiomer. Lambda cigalotrin get out of cyhalothrin, which is produced as a mixture of four isomers in approximately equal amounts, with two isomers are lambda cigalotrin and epimere these two isomers, i.e. R--cyano-3-phenoxybenzyl 1R, 3R-3-/Z-2-chloro-3,3,3-Cryptocom-1-EN-1-yl/ -2,2-cyclopropanecarboxylate and his ananatis) and "Para isomer II".Example 1. Cigalotrin (105 g), wet isopropanol containing 2,7 or 8.0% weight/weight of water (270 g), sodium cyanide (6.5 g) and crystalline lambda cigalotrin loaded into a 1-liter glass reactor, turbine equipped with a glass stirrer and a cooling jacket, maintained at a temperature of -5oC, which is maintained by circulation of chilled mixture of water and ethylene glycol, with stirring for 24 hours, after which the ratio of the Pair of the first isomer /Pair II isomer determined by gas chromatography. The stirring is continued for another 24 hours and make a second determination of the ratio I/II.The results listed in the table in comparison with the results obtained in similar experiments, in which instead of the cyanide present Diisopropylamine.The table shows that the use of cyanide allows you to complete the method after 24 hours, while the use of amine requires a much longer period to achieve the same end result. 1. The method of obtaining the lambda-cyhalothrin in the form of a racemic modification, containing S--cyano-3-phenoxybenzyl - 1R,3R - 3-(Z-2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylate and its enantiomer, including education, components lambda-cigalotrin and epimer of these two isomers in solution or in suspension in isopropanol, wherein the treatment is carried out in the wet isopropanol containing 2 to 15% vol. water, sodium cyanide, taken in an amount of 0.5 to 15.0 mol.% the number of cyhalothrin, at a temperature of -10o... +20oC.2. The method according to p. 1, characterized in that epimer obtained industrially in a mixture with isomers.3. The method according to p. 1, characterized in that the cyanide is used in solid form.4. The method according to p. 1, characterized in that the cyanide is used in the form of an aqueous solution in the presence of a catalyst phase transfer.
< / BR>where R is the ester residue, split in neutral or acid medium and which WITH1-18the alkyl possibly substituted with halogen or benzyl radical, possibly substituted on the tops of the aromatic ring by one or more halogen atoms, or a radical of formula (a) -(g),
< / BR>where R2Is h or methyl;
R4- CN, N.;
R5- fluorine, chlorine, bromine or hydrogen;
R6, R7, R8, R9is hydrogen or methyl;
S/1 symbolizes tetrahedrite
-cyano-3-phenoxybenzyl 1r, 3s - 2,2-dimethyl-3-(2 - chloropropene-1-yl)-cyclopropanecarboxylic in the form of a mixture of isomers exhibiting insect-acaricide and larvicidal activity" target="_blank">
in the form of indivisible mixture of isomers Ia and IB in the ratio from 1:2 to 1:4
< / BR>4-Methyl-2'-cyanobiphenyl can find wide application as an intermediate product in the synthesis of derivatives of biphenylmethane described in applications EP-A-O 253310 and A
Owith this ratio of isomers obtained by asymmetric transformation
FIELD: special methods in organic synthesis.
SUBSTANCE: known drug: racemic 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol, briefly called propranolol, is converted into propranolol hydrofluoride, which is dissolved in ethanol at 55-70оС to form concentrated solution. The latter is gradually cooled to 20-26оС, after which is added seed of one of enantiomers, solution is stirred for 30-60 min, filtered non-racemic propranolol hydrofluoride enantiomer having the same configuration as the seed previously added. Racemic compound is added to mother liquor in amount compensating separated precipitate, mother liquor is heated at 55-70оС to entirely dissolve added material and seed of the other enantiomer is added. Subsequent crystallization gives precipitate rich in the other enantiomer and process is several times repeated. Enantiomer purity is then raised by recrystallization. Non-racemic propranolol salts are finally converted into free propranolol enantiomers. Method of invention can be used in pharmaceutical practice.
EFFECT: enabled involvement method-assisted preparation of non-racemic propranolol.
FIELD: organic chemistry.
SUBSTANCE: invention relates to chiral N-acetyl-alpha-amino acid salts and optically active beta-aminoalkylnitriles, in particular compound of formula IIa , wherein R is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; Q is N-acetyl-alpha-amino acid. Also invention relates to method for conversion of racemic 3-amino-(C3-C7)-alkylnitrile of formula I to corresponding (R) isomer of formula IIf. Claimed method includes interaction of racemic 3-amino-(C3-C7)-alkylnitrile of formula I with N-acetyl-alpha-amino acid of formula Q in solvent. Also disclosed is method for conversion of R or S 3-amino-(C3-C7)-alkylnitrile to racemic 3-amino-(C3-C7)-alkylnitrile by interaction of R or S 3-amino-(C3-C7)-alkylnitrile with aqueous ammonia at 30-200°C. Composition useful as structure units in synthesis of optically active beta-amino acids, enriched with compound of formula IIa and compound of formula I, wherein Q is N-acetyl-alpha-amino acid; and R is as defined above also are disclosed.
EFFECT: new method for separation of 3-aminoalkylnitryles.
2 dwg, 8 ex
FIELD: chemistry of optically active compounds.
SUBSTANCE: invention concerns separation of chiral sulfoxides, which are widely used in synthesis of chiral organic compounds, and describes homochiral organometallic microporous polymeric material capable of enantio-selective sorption of sulfoxides. A method for chromatographic separation of chiral sulfoxides on column filled with indicated material as chiral fixed phase is developed.
EFFECT: expanded possibilities of chiral compounds' separation.
4 dwg, 2 tbl
SUBSTANCE: invention relates to chemistry of organic compounds, namely, to method of division into separate enantiomers of racemic 1-carbamoyloxy-2-hydroxy-3-(2-methoxyphenoxy)propane and lies in the following: at 50-55°C saturated water solution of racemic 1-carbamoyloxy-2-hydroxy-3-(2-methoxyphenoxy)propane, enriched with one of enentiomers, is prepared, mixed with gradual cooling to room temperature, achieving its supersaturation, after that crystalline seeding of the same enantiomer, which is added for enrichment, is introduced, kept while mixing and thermostating until maximal value of enantiomer excess of mother liquor is reached, scalemic 1-carbamoyloxy-2-hydroxy-3-(2-methoxyphenoxy)propane, possessing the same configuration as the sample of introduced seeding, is filtered; racemic compound is added into mother liquor, enriched with the second enantiomer, in amount that compensates separated sediment, heated to complete dissolution at 50-55°C, after that cooled to room temperature ensuring supersaturation, crystalline seeding of prevailing in solution enantiomer is introduced, kept while mixing and thermostating, sediment, enriched with the second enantiomer is separated with further repetition of said process for several times, with thorough analysis of enantiomer purity of target compound.
EFFECT: ensuring possibility to obtain enantiomers of methocarbamole (1-carbamoyloxy-2-hydroxy-3-(2-methoxyphenoxy)propane) of high optic purity from racemic mixture.
1 cl, 3 ex, 2 tbl
SUBSTANCE: method involves 1) dividing a racemate into two pure enantiomers via chromatographic separation on a chiral polysaccharide as a stationary phase with alcohol as the mobile phase and sorption of the eutomer, 2) repeated racemisation of the distomer with a base using a catalyst in a solvent selected from ether or a mixture of solvents containing ether, at temperature between 80°C and 120°C and 3) subjecting the obtained racemate to separation at step 1) in a repeated cycle. The invention also pertains to use of a pure S-enantiomeric form of a formula I compound, particularly (-)-(S)-N-(1-cyano-2-(5-cyano-2-trifluoromethylphenoxy)-1-methylethyl)-4-trifluoromethylsulfanylbenzamide, for control of entozoic parasites of warm-blooded animals, such as helminths.
EFFECT: efficient method of producing a unique enantiomer from a racemate of amidoacetonitrile compound having a formula in which R1, R2 and R3 independently denote cyano, halo-C1-C6alkyl or halo-C1-C6alkylthio.
15 cl, 1 ex