• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A novel crystalline material consisting of a enantiomeric pair of cyhalothrin isomers in the form of the racemic mixture and having greater insecticidal activity than cyhalothrin itself is described, together with a process for obtaining the enantiomeric pair of isomers by crystallization from concentrated cyhalothrin solutions in lower alkanols or liquid alkanes.
    公开号:SU1225483A3
    申请号:SU833652706
    申请日:1983-10-10
    公开日:1986-04-15
    发明作者:Джон Робсон Майкл；Кросби Джон
    申请人:Империал Кемикал Индастриз Плс (Фирма)；
    IPC主号:
    专利说明:

    f
    The invention relates to a process for the preparation of a new enantiomer. A pair of isomers of cyhalothrinas-cyano-3-phenoxy-sibenzyl ester cis-3 - (2-2-chloro-3, 3,3-trifluoroprop-1-en-1-yl) - 252-dimethylcyclopropanecarboxylic acid, namely (8) -c / -cyano-3-phenoxy-benzyl ester (1 R, cis) -3- (E-3-chloro-3.3 5 3-trifluoroprop-1- en 1- -yl) -2., 2-dimethylcyclopropanoic acid (1 R, cis-3-isomer) and (R) o-cyano-3 phenoxybenzyl ester (1 S,. cis) 3- (Z-2 -chloro-3,3 S 3-trifluoroprop-) -2,2-dimethylcyclopropanoic acid, (1 S, cis-K-isomer), which can be used as an insecticide,
    Tsigalotrin is a mixture of four 1–13 isomers:
    Isomer A is an ester of 1 R, cis-acid and L (8) -alcohol l R, cis-Sj; Isomer B is an ester of 1 S, cis-acids and C. (k) -alcohol 1 S, Isomer B is a ester of 1 R, cis-acids and ut- (R) -alcohol P R c: isk-1;
    Isomer G is an ester of 1 S, cis-α-acids and (8) -alcohol, L1 S, cis-s
    It sodernsite, as a rule, from 40 to 60% by weight of isomers A and B and 40-60% of isomers C and G.
    The purpose of the invention is to find isomeric derivatives of cyclopropanecarboxylic acid and phenoxybenzyl alcohol with a compound with a similar structure and analogue purpose, which have a higher activity than the known compounds. The target product according to the proposed method is obtained in two different forms: product 1 and product Po. Usually product 1 precipitates, very slowly (from 7 to 15 days), IT product. - faster (from 1 to 6 days),
    If the added seed crystals of an enantiomeric pair of isomers are obtained by separation using high pressure liquid chromatography (LC), the target pair of isomers is obtained as product 1, which is a white crystalline precipitate with mp. 36-42 ° C; if it is free from impurities, then 41-42 ° C.
    Infrared spectral analysis shows that it consists of a conglomerate of mixed crystals, in which each crystal consists of molecules of a single isomer with approximately


    .
    s
    225483
    the same number of crystals that are fine needles of each isomer, i.e. Product 1 is a racemic mixture. If crystals
    The 5 zantiomeric pairs of isomers, which are obtained by the separation of cyt alotrin using high-pressure LC, are recrystallized several times and used as seed
    10 crystals, get the product II with so pl. 48-50 ° C.
    The data of IR spectroscopy and X-ray diffraction analysis show that each individual crystal has a PI3 equal amounts of each isomer regularly arranged in a crystal. 11G lattice. This product form is a racemic compound.
    30 Data for the crystalline form of PRODUCT II is obtained by examining the X-ray diffraction characteristics of a crystal having a size of about 0.13-0.13
    25 0.12 mm, using a Philips PW 1100 X-ray diffractometer, using Mo-K. radiation from graphite30
    35
    40
    45
    50
    55
    monochromator. Scanning 6-20 is performed at an Oj5 scanning speed of 0.8 ° scanning width and reflexes of 3 4 0 6 25 °
    The resulting product II is as follows:
    crystalline form: MONORESLIN-, space group: C2 / s, and 34.764 (5), b 7.023 (2), c 18.624 (3) A; p 101.95 (3) °; and 4448.46 8; density 1,343-g / cm- -. F (OOO) 1856; (Mo-K) 1.77 Sh9-K) 0.71069 A °.
    The crystal lattice consists of regularly arranged alternating molecules of two isomers A and B, in each of which the trifluoromethyl group is in a trans position relative to the cyclopropane group across the double bond (m.k. K-configuration). The elementary cell contains the four molecules of each enantiomeric isomer.
    Example 1. Separation of but-3-phenoxybenzyl ester (.cis) -3- (2-2-chloro 3,3,3-trifluoroprop-1-1--1yl) -2, 2-dimethylcyclopropanoic acid on its compound enantiomeric isomers.
    The material to be separated is characterized by thin-layer chromatography of the sample on silica gel
    0.25 mm thick plates (analytical grade) using various eluents. Two components are isolated, corresponding to two pairs of variable enantiometers. The mean Rf values for the two components are listed in Table. one.
    Table 1
    The separation of the material is carried out by high performance liquid chromatography using a device equipped with a silica gel column. Column is charged with 0.5 g of dihalotrin, consisting of (55:45) 1 S, cis-S / 1 R, cis-a: 1K, cis-8/18, cis-R enantiomeric pairs. The eluent is a mixture of diethyl ether / / petroleum ether (boiling range 40-60 ° C) (1: 9), and a feed rate of 0.2 liters per minute. Fractions are collected after four recycles. The first fraction is identified by proton magnetic resonance as 1 R, cis-R / .l S, cis-S enantiomeric pair, and the second fraction, as 1 R,. Cis-S / l S, pic-R enantiomeric pair. Each fraction has a purity of 98%, and together they correspond to 60% of the amount injected. NMR data are given in Table. 2 (Values in DM C1).
    Table 2


    (d)
    (m)
    (S)
    1.34 (S)
    1.98 2.07 2.19 2.29 2.38
    6.32
    (m)
    (S)
    1225483
    11 OD 5: 1 W-§- tab. 2

    (d)
    6.77
    6.87
    (d)
    ten
    6.97-7.50 (m) 6.97-7.50 (m)
    P TJ and M e p 2. Crystallization of 1 R, cis-S / l S, cis-R. enantiomeric pair of a solution of cyhalothrin. The crystals used for the seed are prepared analogously to example 1.
    455.6 g of a mixture of 3- (Z-2-chloro-3, 3,3-trifluoroprop-1-en-1-yl) -2,2-dimethylcyclopropanoic acid d-cyano-3-phenoxybenzyl ester cis-isomer containing 43.2% by weight of 1 R, cis-S and 1 S, cis-R isomers and 56.8% by weight of 1 S, cis-S and 1R, cis-R isomers, dissolved in 460 ml of isopropane nola (cyhalothrin: solvent ratio 1: 1), which is pre-dried by distilling from calcium hydride. The dissolution is carried out by heating the mixture to about 50 ° C. The solution is cooled to 3 ° C while being stirred with a magnetic stirrer coated with polytetrafluoroethylene, then several crystals (500 mg) of 1R, cis-S and IS, cis-R isomers of o (-cyano-3-phenoxybenzyl ester 3 - (Z-2-chlorop-3,3,3-tri-thifoprop-1-ene-1-yl) -2,2-dimesh-cyclopropanoic acid. Stirring is continued at this temperature for 9 days, then the suspension is cooled to - 10 ° C and intensively mixed with a polytetrafluoroethylene stirrer
    within 7 days.
    The precipitated solid is removed at 3 ° C, dried under suction, rinsed once 100 ml
    petroleum ether (40-60) at 3 ° C and dried to constant weight in a vacuum desiccator over phosphorus pentoxide to obtain 97.6 g of white crystals. As the gas-liquid shows.
    on capillary chromatography, this product contains a 86.9% by weight 1: 1 mixture of 1R, cis-S and 15, cis-R isomers of the starting material. The solid substance is dissolved in 300 ml of anhydrous petroleum ether (40-50), solution o; Sladsayat until with stirring; and a few crystals of a mixture of 1R, cis-S and 13, cis-K isomers N-cyano-3-phenoxybenzyl ester of 3- (Z-2-chloroproxy-3,35 3-trifluoropropyl) are added as seeds. 1-en-1-yl) -2,2-dimethylcyclopropanoic acid. After 2 h, the obtained white suspension is filtered off at 3 ° C and the solid is dried with suction. Then, by drying in a vacuum desiccator over phosphorus pentoxide, 73.6 g (70%) of a white solid containing 92% by weight of a mixture of 1K, cis - is obtained. 3 and 1.3, cis-K isomers d of cyano-3-phenoxybenzyl ester 3- (Z-2-chloro-C 5 3,3-trifluoroprop-1-e--1-yl) -2, 2 dimethylcyclopropanoic acid, having so pl. within . 36-42 ° C
    The IR spectrum shows that it is a conglomerate or a racemic mixture (product 1).
    Example 3. A mixture of isomers of cyhalothrin; consisting of 6.4 g of 1R, cis-S isomer; 6.4 g IS, cis-R isomer; 3.2 g of IS, cis-S isomerais, 2 g of IPvjcis-R isomer, dissolved in n-hexane (20 ml) (cyhalothrin: solvent ratio 1: 1) and stirred in a nitrogen atmosphere, simultaneously cooling at 5 ° C. After dissolving and cooling, 5 mg of the racemic mixture (prepared according to Example 2) is added, followed by purification by recrystallization until the melting point is 41.5-42.0 ° C. Stirring is carried out for 16 hours at -: C. The precipitated solid is collected by filtration on a funnel with a stationary filter cooled to 0 ° C and washed twice with hexane, oh: precipitated to -5 ° C. 9.30 g (70%) of product are obtained with a melting point of 48-49.5 ° C, having a purity of at least 99% with respect to the cygalothrine isomers and consisting of not less than 96.3% of 1R, cis -S and IS, cis-R isomers in equal proportions.
    Infrared analysis shows that this product is different from the product of example 2. The crystalline form is also different (diamond-shaped, not needle),
    and this, in combination with a higher melting point, shows that it is a racemic compound in which individual crystals contain equal amounts of 1D, and IS, cis-R isomers, the molecules of each of which are arranged regularly in a crystal lattice,
    IR spectrum (Isidka paraffin mixture): 1050, 1030, 1010, 990, 970 (shoulder), 963, 950, 935, 920, 908, 904, 895, 888, 873, 838., 830 (shoulder) 820, 805 , 795, 785, 760, 748, 725, 702, 695, 650 cm,
    Example 4, Mixture of cyhalotrino isomers, consisting of 20.61 g of isomer A 20.61 g of isomer B; 4.04 g of isomer B and 4.04 g of isomer D, dissolved in warm hexane (100 NUI) (cyhalothrin: hexane ratio 1: 2) are cooled to 5 ° C and 25 mg of the product of Example 3 is added. Then the mixture is slowly cooled to -5 ° C with vigorous stirring.
    The precipitate is collected by filtration, washed on the filter with cold hexane, and dried in air to give the racemic compound 1R, cis-S and IS, cis-R isomers (28.6 g, 69.1%), t, pl. 49-50 ° C.
    Example 5. The effect of different solvents, the proportions of the solids and cyhalothrin, the periods of time and the temperatures on the yield and the amount of the product in the form of a racemic mixture (product 1). The cyhalothrin used contains 42% (+ 1%) 1R, nHc-S / 1S, cis-R enantiomeric pair of isomers. In each experiment, a few milligrams of crystals of the racemic mixture are added after cooling to the desired temperature to initiate nucleation. The results are shown in Table 3,
    Example 6, Deposition of the racemic form of the product compound (product II), Technical cyhalothrin mixture (200 g), purity 95.8% by weight, and isopropanol (200 ml) (cyhalothrin: solvent ratio 1: 1) are loaded into a round bottom glass flask containing a series of glass beads, cooled to -5 ° C, and crystals of the racemic compound (4.0 g) are added. The cooled mixture is stirred for 23 hours at −5 ° C. The precipitate is collected by pouring the stirred.
    the mixture on a pre-cooled sintered filter at -5 ° C, and the filter residue is washed by suspending with pre-cooled n-hexane (one volume
     The amount of seed crystals is equal to 20.0 g (in all other examples, the amount of addition of seed crystals is from 25 to 100 mg.
     After recrystallization from petroleum ether (40-60 C), the amount of seed crystals is tO g.
    And Excluded the weight of seed crystals +4.0 g of added seed crystals.
    layer), having obtained (after drying) a com pound compound consisting of 1R, cis-S and IS, cis-R of cyhaloline isomers (39.5 g, 46.7%), so pl. 49,
    Table 3
    Comparative data on insects
    cid activity for the enantiomeric pair of isomers IRj cis-S and IS, cis-R cygalothrine;; mm permethrin testifies to a higher level of activity of the enantiomeric pair of isomers in the determination of
    the values of LK (concentration, h, / mpn which, when processing leaves, ensure the defeat of 50% of the leaf-eating pest population) on the larvae of the pest Heliothis Virenens (tobacco worm, cotton pest) and Chillo pavtellus (pest of corn and sorghum)
    The data presented in Table. BUT.
    Table 4
    Insecticidal activity in the determination of LC, ppm, in the ratio
    Heliothis
    .one.
    Chillo
    权利要求:
    Claims (1)
    [1]
    METHOD FOR PRODUCING A CRYSTALLINE ENANTIOMERIC PAIR OF (S) -c (-CYANO-3-PHENOXI ISOMERS. IL) -2,2-DIMETHYL CYCLOPROPANIC ACID AND (R) -ot-CYANO-3-PHENOXYBENZyl ETHER (1S, CIS) -3- (Z-2-CHLOR-3,3,3-TRIFTOROPROP-1-EN-1 -YL) -2,2-DIMETHYL CYCLOPRO PANIC ACID, with the result of the fact that about (-cyano-3-phenoxybenzyl ether 3- (2-chloro-3,3,3-trifluoroprop -1-en-1-yl) -2,2-dimetiltsiklopropanovoy acid is dissolved in an organic solvent selected from C z -C 5 -alkanols or C ^ -Sdalkanov at a weight ratio of 1: 2.1, the resulting p the target is cooled to (-10) - (+5) ° С, seed crystals of the enantiomeric pair of isomers are added so that they remain insoluble, after which the solution is kept at the indicated temperature for 0.4-33 days, the precipitated crystals are separated or, if recrystallize as needed.
    SU, „> 1225483 f
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4183948A|1977-01-24|1980-01-15|Imperial Chemical Industries Limited|Halogenated esters|
    GB2000764B|1977-03-23|1982-04-28|Ici Ltd|Halogenated esters|
    BE886160A|1979-11-27|1981-05-14|Shell Int Research|CYCLOPROPANIC CARBONIC ACID ESTER DERIVATIVES|GB8418331D0|1984-07-18|1984-08-22|Ici Plc|Insecticidal ester|
    CA1275108A|1985-01-16|1990-10-09|Laszlo Pap|Insecticidal composition comprising more than oneactive ingredients|
    DE19953775A1|1999-11-09|2001-05-10|Bayer Ag|Active ingredient combinations with insecticidal and acaricidal properties|
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    GB0229803D0|2002-12-20|2003-01-29|Syngenta Ltd|Chemical process|
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    法律状态:
    优先权:
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    MD94-0229A| MD205C2|1982-10-11|1994-05-25|Method of preparation of the crystal enantiamorfous pair of isomers of -a-cyano-3--3-2,2 dimethylcyclopropane acid and - )-a-cyano-3-phenoxybenzilic ether -3--2,2-dimethylcyclopropanic acid.|
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