CN1944409A - Method for preparing haloxyfop-P-methyl with high optic purity - Google Patents
Method for preparing haloxyfop-P-methyl with high optic purity Download PDFInfo
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- CN1944409A CN1944409A CN 200610154456 CN200610154456A CN1944409A CN 1944409 A CN1944409 A CN 1944409A CN 200610154456 CN200610154456 CN 200610154456 CN 200610154456 A CN200610154456 A CN 200610154456A CN 1944409 A CN1944409 A CN 1944409A
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Abstract
The process of preparing haloxyfop-R-methyl in high optical purity includes the following steps: 1. the reaction of 2, 3-dichloro-5-trifluoro methyl pyridine and hydroquinone as initial material in the presence of K2CO3 in N, N-dimethyl formamide at 105-110 deg.c; separating and purifying after finishing reaction to obtain the intermediate 3-chloro-2-(4-hydroxy phenoxy)-5-trifluoro methyl pyridine; and 2. nucleophilic substitution reaction of 3-chloro-2-(4-hydroxy phenoxy)-5-trifluoro methyl pyridine and (L)-2-metylsulfonyl oxy methyl propionate in chlorobenzene solvent in the presence of K2CO3, at 70-110 deg.c, and post-treatment after reaction. The prepared haloxyfop-R-methyl has relatively high optical purity and ee value higher than 92 %.
Description
(1) technical field
The present invention relates to a kind of method with high-optical-purity haloxyfopPmethyl.Particularly with 2,3-two chloro-5-5-flumethiazines, Resorcinol are starting raw material, with K
2CO
3Be alkali, at N, reaction obtains 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine in the dinethylformamide (DMF), then this intermediate with (L)-2-mesyloxy methyl propionate is further with K
2CO
3Be alkali, reaction obtains the target compound haloxyfopPmethyl in chlorobenzene.
(2) background technology
HaloxyfopPmethyl claims haloxyfop-r-methyl again, chemistry R-(+) by name-2-{4-[3-chloro-5-(trifluoromethyl)-2-pyridyloxy] phenoxy group } methyl propionate, molecular structural formula is:
HaloxyfopPmethyl is a kind of important fragrant phenoxy propionic acid ester weedicide, have characteristics such as efficient, highly selective, low residue, be widely used in soybean, cotton, peanut, rape, vegetables etc., the annual and perennial monocotyledon weed in control and expeling dicotyledonous crops field behind seedling.HaloxyfopPmethyl is the R type isomer of pyrrole fluorine chlorine standing grain spirit, and the S type isomer of pyrrole fluorine chlorine standing grain spirit does not almost have activity.Countries in the world are advocated energetically with haloxyfopPmethyl and are replaced the spirit of pyrrole fluorine chlorine standing grain at present, are keeping under the constant prerequisite of drug effect, and the usage quantity of agricultural chemicals can reduce half, both can save the raw materials cost of half, can reduce environmental pollution again.Bibliographical information mainly contains first etherification method and back etherification method about the preparation method of efficient fluazifop, elder generation's etherification method is at first 2,3-two chloro-5-5-flumethiazines and Resorcinol condensation obtain intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, this intermediate further with (L)-2-mesyloxy methyl propionate reaction obtain target product (US4532328, EP0385720).Back etherification method is that at first (S)-2-chloropropionic acid and Resorcinol condensation obtain intermediate (R)-2-(4-hydroxyphenoxy) propionic acid, this intermediate is further with 2, the two step reactions that methylate of 3-two chloro-5-5-flumethiazine condensations, methyl iodide obtain target compound (WO2005/042460, EP0344746, US4897481).Back etherification method can obtain to have the product (the highest ee value is 98.8%) of better optical purity, but main raw material (the S)-domestic non-availability of 2-chloropropionic acid, and the optical purity of the finished product depends on the optical purity of (S)-2-chloropropionic acid, this route reaction step is long simultaneously, the aftertreatment complexity, the raw materials cost height is not suitable for domestic production.The required raw material of elder generation's etherification method is domestic all can conveniently to be obtained, and reactions steps is shorter, and raw materials cost is low, relatively is fit to domestic production.Patent EP0385720 has reported the preparation method of intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, the product that obtains is a reddish-brown oily matter, mainly contain excessive Resorcinol and di-substituted (1 in this oily matter, impurity such as two (the 3-chloro-5-trifluoromethyl-2-pyridyloxy) benzene of 4-, purity is lower, as further reaction, can influence the purity of the finished product.Patent US4532328 reported 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine with (L)-method of 2-mesyloxy methyl propionate prepared in reaction efficient fluazifop, the finished product that this method makes needed column purification and yield low, were not suitable for preparation of industrialization.
(3) summary of the invention
For the preparation purity that overcomes haloxyfopPmethyl in the prior art is low, the deficiency that yield is low the invention provides a kind of preparation method who prepares the high-optical-purity haloxyfopPmethyl.A kind of preparation has the method for high-optical-purity haloxyfopPmethyl, described method is carried out as follows: (1) is with 2,3-two chloro-5-5-flumethiazines, Resorcinol are the starting raw material reaction, and reaction finishes to make intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine by separation and purification; (2) again with described intermediate with (L)-2-mesyloxy methyl propionate reaction makes haloxyfopPmethyl; Described step (2) is specially: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine with (L)-2-mesyloxy methyl propionate is at K
2CO
3For alkali exists down, is that solvent carries out nucleophilic substitution reaction in 70～110 ℃ with the chlorobenzene, reacting completely obtains the target product haloxyfopPmethyl through aftertreatment, the amount of substance that feeds intake ratio: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-and 2-mesyloxy methyl propionate: K
2CO
3Be 1: 1.5～2.5: 1.2～2, the chlorobenzene consumption is counted every gram 6～10ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.
The temperature of reaction that described nucleophilic substitution reaction is recommended is 80～85 ℃, and the reaction times is 48 hours.
Feeding mode at room temperature is added dropwise to 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine and K for (L)-2-mesyloxy methyl propionate
2CO
3Mixed solution in, be that reaction solvent reacts with the chlorobenzene.Reaction solvent also can be DMF, DMSO, N-Methyl pyrrolidone, toluene, benzene in step (2), is reaction solvent but the present invention selects chlorobenzene for use, and the present invention is reaction solvent by a large amount of experiment confirms with the chlorobenzene, and the optical purity of product is the highest.
Reaction formula of the present invention is as follows:
Described step (2) the amount of substance ratio that feeds intake is preferably: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-and 2-mesyloxy methyl propionate: K
2CO
3Be 1: 2: 1.5, the chlorobenzene consumption is counted every gram 8ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.Described step (2) aftertreatment is: after reaction finishes, add entry, be warming up to 60 ℃, stir 30min, abandon water, organic phase washes with water, anhydrous sodium sulfate drying, decompression and solvent recovery, raffinate underpressure distillation, collect 198～201 ℃/1mmHg cut, get colourless being and have the high-optical-purity haloxyfopPmethyl to light yellow oil.Through reprocessed like this target product, HPLC chiral column detection level is usually greater than 95%, and the ee value is greater than 92%.
Above-mentioned preparation has the method for high-optical-purity haloxyfopPmethyl, and described step (1) is specially: 2, and the reaction of 3-two chloro-5-5-flumethiazines and Resorcinol is at K
2CO
3Exist down, in the DMF reaction solvent, carry out nucleophilic substitution reaction, the described amount of substance ratio that feeds intake in 90～120 ℃: 2,3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3Be 1: 1.5～3: 1.5～3.0, with 1: 2.1: 2.1 the best; N, the consumption of dinethylformamide are with 2, and 3-two chloro-5-5-flumethiazines are counted every gram 10～15ml, serve as preferred with every gram 13ml.Reaction finishes, carry out separation and purification: reclaim solvent DMF, remaining dope water dissolution, it is 1～2 that the following dripping hydrochloric acid aqueous solution of stirring makes the pH value, gained solution extracts with toluene, the phase of anhydrating, the saturated common salt water washing of toluene extraction liquid, use gac at 50 ℃～70 ℃ again, use anhydrous sodium sulfate drying after being preferably 60 ℃ of decolourings, concentrating under reduced pressure toluene, the gained viscous fluid dissolves with the sherwood oil reflux, and separating out white to light red solid after the cooling is intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine fusing point is 79-80 ℃, through the intermediate HPLC of above-mentioned separation and purification treatment detection level usually greater than 98%.The residue water recyclable unnecessary Resorcinol of ethyl acetate extraction after the above-mentioned toluene extraction, the water that the residue water after the toluene extraction here just will will be removed originally.
The nucleophilic substitution reaction temperature is for being preferably 105～110 ℃ in the above-mentioned step poly-(1), and the reaction times is 4 hours.
Further, preparing the method with high-optical-purity haloxyfopPmethyl carries out as follows: the reaction of (1) 2,3-two chloro-5-5-flumethiazines and Resorcinol is at K
2CO
3Exist down, in the DMF reaction solvent, carry out nucleophilic substitution reaction, the described amount of substance ratio that feeds intake in 105～110 ℃: 2,3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3It is 1: 2.1: 2.1, react end in 4 hours, carry out separation and purification: reclaim solvent DMF, remaining dope water dissolution, it is 1～2 that the following dripping hydrochloric acid aqueous solution of stirring makes the pH value, gained solution extracts with toluene, the saturated common salt water washing of toluene extraction liquid, after 60 ℃ of decolourings, use anhydrous sodium sulfate drying with gac again, concentrating under reduced pressure toluene, the gained viscous fluid dissolves with the sherwood oil reflux, and separating out white to light red solid after the cooling is 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, and above-mentioned toluene extracted residual water reclaims excessive Resorcinol with ethyl acetate extraction;
(2) (L)-2-mesyloxy methyl propionate at room temperature is added dropwise to 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine and K
2CO
3Mixed solution in, in 80～85 ℃, be that solvent carries out nucleophilic substitution reaction with the chlorobenzene, the described amount of substance ratio that feeds intake is: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-2-mesyloxy methyl propionate: K
2CO
3Be 1: 2: 1.5, the chlorobenzene consumption is counted every gram 8ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, reacts 48 hours, carry out aftertreatment: reaction solution adds entry, be warming up to 60 ℃, stir 30min, abandon water, organic phase washes with water, anhydrous sodium sulfate drying, decompression and solvent recovery, raffinate underpressure distillation, collect 198～201 ℃/1mmHg cut, get colourless being and have the high-optical-purity haloxyfopPmethyl to light yellow oil.
This patent finds with the chlorobenzene to be reaction solvent by the selection to a large amount of reaction solvents in the step (2), and the ee value of product is best, reaches 92%.And, can remove excessive (L)-2-mesyloxy methyl propionate by simple aftertreatment, and need not pass through the chromatographic column purifying, can obtain purity greater than 95% product, separation yield is greater than 96%.Patent US4532328 reported 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine with (L)-2-mesyloxy methyl propionate is with K
2CO
3Be alkali, the operational path of prepared in reaction haloxyfopPmethyl in methyl-sulphoxide (DMSO), product is by the chromatographic column purifying, and separation yield is 78%, and its optical purity is passed through
1It is 90% that HNMR measures the ee value.We by the optical purity of HPLC chiral column mensuration the finished product, find that the ee value only is 74% according to the method for this patent.
The present invention is also by the separation purification method in the optimization step (1), successfully separated impurity, obtain 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine solid, HPLC measures purity greater than 98%, improved the purity of this intermediate greatly, and reclaimed excessive Resorcinol, further reduced cost.
The present invention compared with prior art has the following advantages:
Intermediate with (L)-2-mesyloxy methyl propionate reaction makes haloxyfopPmethyl, this technology is reaction solvent with the chlorobenzene, has improved the optical purity of target product greatly, the ee value is greater than 92%.
2. the reaction solution in this technology poly-to going on foot (2) adopts 60 ℃ soda lye wash, can remove unnecessary raw material (L)-2-mesyloxy methyl propionate, and aftertreatment is simple, the target product purity height that obtains, and main content is greater than 95%.
3. this process using toluene is extraction agent, intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine can be separated with unnecessary raw material Resorcinol, and the excessive Resorcinol of aqueous phase is reclaimed with ethyl acetate extraction, has reduced production cost.
3. this process using sherwood oil recrystallization intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, it is di-substituted to remove a small amount of Resorcinol that dereaction produces, and has improved the purity of this intermediate.
(4) embodiment
The invention will be further described below in conjunction with embodiment, but protection scope of the present invention is not limited to this.
Embodiment 1
The preparation of 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: in the 500ml there-necked flask, add 23.1g (0.21mol) Resorcinol successively; 21.6g (0.1mol) 2.3-two chloro-5-5-flumethiazines; 281mlDMF and 29.0g (0.21mol) salt of wormwood, nitrogen protection stir down and are warming up to 105～110 ℃ of reactions 4 hours.Be cooled to room temperature and filter mother liquor decompression and solvent recovery DMF.The gained viscous fluid adds the 200ml water dissolution, and stirring down and being acidified to pH value with 5% aqueous hydrochloric acid is 1～2, uses 100ml toluene to extract 3 times.Merge organic phase,, add 60 ℃ of decolourings of 10g gac 1～2 hour, filtered while hot, cooling back toluene liquid anhydrous sodium sulfate drying with 100ml saturated common salt water washing 2 times.Concentrating under reduced pressure reclaims toluene, and the gained viscous fluid adds the 400ml sherwood oil, and the reflux dissolving slowly is cooled to room temperature, separates out white to light red solid 27.2g.Measure fusing point: 79-80 ℃, HPLC measures content 98.7%, yield 93.8%.IR(KBr)：3349，2928，1665，1608，1508，1461cm
-1；
1H?NMR(CDCl
3)δ8.27(1H，s)，7.97(1H，s)，6.86~7.05(4H，q)，4.97(1H，s)；MS(m/e)：289。Described white to pale red solid is 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.
Water 100ml ethyl acetate extraction 2 times after the toluene extraction are steamed and are removed ethyl acetate, reclaim and obtain the 10.3g Resorcinol.
Embodiment 2
The preparation of 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: except the amount of substance ratio that feeds intake is 2,3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3=1: outside 1.5: 1.5, other operational condition is all identical with embodiment 1, gets white to light red solid 23.4g, yield 80.7%, purity 98.3%.
Embodiment 3
The preparation of 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: except temperature of reaction is 90～95 ℃, reaction times is outside 9 hours, and other operational condition is all identical with embodiment 1, gets white to light red solid 25.6g, yield 88.3%, purity 98.0%.
Embodiment 4
3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine preparation: except the amount of substance ratio that feeds intake is 2,3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3=1: 3: 3, the DMF consumption was outside the 324ml, and other operational condition is all identical with embodiment 1, got white to light red solid 27.0g, yield 93.1%, purity 97.7%.
Embodiment 5
HaloxyfopPmethyl preparation: in the 250ml there-necked flask, add 10.4g (0.075mol) salt of wormwood, 14.5g (0.05mol) 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, the 116ml chlorobenzene, stirred under the room temperature 15 minutes, slowly drip in 30 minutes 18.2g (0.1mol) (L)-2-mesyloxy methyl propionate.Drip and finish, be warming up to 80～85 ℃ and continue reaction 48 hours.Naturally cool to room temperature, add 80ml water, be warming up to 60 ℃, stirred 30 minutes, cooling is standing demix afterwards, and organic phase is with 2 * 100ml water washing, anhydrous sodium sulfate drying.Concentrating under reduced pressure reclaims chlorobenzene, and 161～162 ℃/1mmHg cut is collected in the raffinate underpressure distillation, colourless to light yellow oil 18.1g, i.e. haloxyfopPmethyl, yield 96.5%.The HPLC chiral column detects purity 95.8%, ee value 92.8%.IR(KBr)：1758，1607，1505，1460，1325cm
-1；
1H?NMR(CDCl
3)δ8.26(1H，s)，7.96(1H，s)，6.92~7.09(4H，q)，4.74～4.79(1H，q)，3.78(3H，s)，1.63～1.65(3H，d)；MS(m/e)：375。
Embodiment 6
HaloxyfopPmethyl preparation: except feeding intake amount of substance than being 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-2-mesyloxy methyl propionate: K
2CO
3=1: outside 1.5: 1.2,, other operational condition is all identical with embodiment 5, colourless to light yellow oil 15.7g, i.e. haloxyfopPmethyl, yield 83.7%, purity 95.2%, ee value 92.5%.
Embodiment 7
HaloxyfopPmethyl preparation: except feeding intake amount of substance than being 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-2-mesyloxy methyl propionate: K
2CO
3=1: 2.5: 2, the consumption of chlorobenzene was 145ml, and temperature of reaction is 105～110 ℃ of reactions 40 hours, other operational condition is all identical with embodiment 5, gets colourless to light yellow oil 17.8g, i.e. haloxyfopPmethyl, yield 94.9%, purity 93.0%, ee value 91.2%.
Embodiment 8-12 is the comparative example with other organic solvent that is different from chlorobenzene, because reaction solvent character differs very big, in some solvent, react, raw material promptly transforms fully under the short period at lesser temps, can increase impurity as heating up again, so generally do not heat up, and the reaction times mainly decides by the conversion of HPLC detection raw material, so the temperature of reaction of embodiment 8-12 and reaction times and example 6 difficult unifications.
Embodiment 8
The preparation of haloxyfopPmethyl: except reaction solvent is a toluene, temperature of reaction is reflux (110 ℃), outside 36 hours reaction times, other operational condition is all identical with embodiment 5, colourless to light yellow oil 16.lg, i.e. haloxyfopPmethyl, yield 85.9%, purity 91.2%, ee value 83.5%.
Embodiment 9
The preparation of haloxyfopPmethyl: except reaction solvent is a benzene, temperature of reaction is reflux (80 ℃), reaction times is outside 60 hours, other operational condition is all identical with embodiment 5, colourless to light yellow oil 14.1g, i.e. haloxyfopPmethyl, yield 75.2%, purity 93.7%, ee value 88.3%.
Embodiment 10
The preparation of haloxyfopPmethyl: except reaction solvent is DMF, temperature of reaction is 25～30 ℃, and the reaction times is 4 hours, after reaction finishes, concentrating under reduced pressure DMF, raffinate adds outside the 100ml chlorobenzene, and other operational condition is all identical with embodiment 5, gets colourless to light yellow oil 18.2g, it is haloxyfopPmethyl, yield 97.1%, purity 87.2%, ee value 75.6%.
Embodiment 11
The preparation of haloxyfopPmethyl: except reaction solvent is DMSO, temperature of reaction is 25～30 ℃, and the reaction times is 5 hours, after reaction finishes, concentrating under reduced pressure DMSO, raffinate adds outside the 100ml chlorobenzene, and other operational condition is all identical with embodiment 5, gets colourless to light yellow oil 17.9g, it is haloxyfopPmethyl, yield 95.5%, purity 86.2%, ee value 74.1%.
Embodiment 12
The preparation of haloxyfopPmethyl: except reaction solvent is a N-Methyl pyrrolidone, temperature of reaction is 25～30 ℃, and the reaction times is 10 hours, after reaction finishes, the concentrating under reduced pressure N-Methyl pyrrolidone, raffinate adds outside the 100ml chlorobenzene, and other operational condition is all identical with embodiment 5, gets colourless to light yellow oil 18.0g, it is haloxyfopPmethyl, yield 96.0%, purity 85.9%, ee value 72.6%.
Claims (10)
1. one kind prepares the method with high-optical-purity haloxyfopPmethyl, described method is carried out as follows: (1) is with 2,3-two chloro-5-5-flumethiazines, Resorcinol are the starting raw material reaction, and reaction finishes to make intermediate 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine by separation and purification; (2) again with described intermediate with (L)-2-mesyloxy methyl propionate reaction makes haloxyfopPmethyl; It is characterized in that described step (2) is: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine with (L)-2-mesyloxy methyl propionate is at K
2CO
3For alkali exists down, is that solvent carries out nucleophilic substitution reaction in 70～110 ℃ with the chlorobenzene, reacting completely obtains the target product haloxyfopPmethyl through aftertreatment, the amount of substance that feeds intake ratio: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-and 2-mesyloxy methyl propionate: K
2CO
3Be 1: 1.5～2.5: 1.2～2, described chlorobenzene consumption is counted every gram 6～10ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.
2. preparation as claimed in claim 1 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that in the described step (2), the temperature of reaction of described nucleophilic substitution reaction is 80～85 ℃, and the reaction times is 48 hours.
3. preparation as claimed in claim 1 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that described step (2) the amount of substance ratio that feeds intake is: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-and 2-mesyloxy methyl propionate: K
2CO
3Be 1: 2: 1.5, described chlorobenzene consumption is counted every gram 8ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.
4. preparation as claimed in claim 1 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that described step (2) aftertreatment is: reaction adds entry after finishing, and is warming up to 60 ℃, stir 30min, abandon water, organic phase washes with water, anhydrous sodium sulfate drying, decompression and solvent recovery, 198～201 ℃/1mmHg cut is collected in the raffinate underpressure distillation, gets colourless being to light yellow oil and has the high-optical-purity haloxyfopPmethyl.
5. preparation as claimed in claim 1 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that described step (1) is: 2, and the reaction of 3-two chloro-5-5-flumethiazines and Resorcinol is at K
2CO
3Exist down,, carry out nucleophilic substitution reaction, the described amount of substance ratio that feeds intake in 90～120 ℃ in the dinethylformamide solvent at N: 2,3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3Be 1: 1.5～3: 1.5～3.0; N, the consumption of dinethylformamide is with 2,3-two chloro-5-5-flumethiazines are counted every gram 10～15ml, reaction finishes, carry out separation and purification: reclaim solvent N, dinethylformamide, remaining dope water dissolution, it is 1～2 that the following dripping hydrochloric acid aqueous solution of stirring makes the pH value, gained solution extracts with toluene, the phase of anhydrating, the saturated common salt water washing of toluene extraction liquid is used anhydrous sodium sulfate drying, concentrating under reduced pressure toluene with gac again after 50 ℃～70 ℃ decolourings, the gained viscous fluid dissolves with the sherwood oil reflux, and separating out white or light red solid after the cooling is 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine.
6. preparation as claimed in claim 5 has the method for high-optical-purity haloxyfopPmethyl, when it is characterized in that the separation and purification in the described step (1), reclaim solvent N, remaining dope water dissolution behind the dinethylformamide, it is 1～2 that the following dripping hydrochloric acid aqueous solution of stirring makes the pH value, and temperature is controlled at 60 ℃ during activated carbon decolorizing.
7. preparation as claimed in claim 5 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that after the extraction of described toluene water with ethyl acetate extraction reclaim Resorcinol.
8. preparation as claimed in claim 5 has the method for high-optical-purity haloxyfopPmethyl, the amount of substance that it is characterized in that feeding intake in the described step (1) ratio: 2, and 3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3Be 1: 2.1: 2.1, N, the consumption of dinethylformamide are with 2, and 3-two chloro-5-5-flumethiazines are counted every gram 13ml.
9. preparation as claimed in claim 5 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that poly-(1) nucleophilic substitution reaction solvent of described step is N, dinethylformamide, and temperature of reaction is 105～110 ℃, the reaction times is 4 hours.
10. preparation as claimed in claim 1 has the method for high-optical-purity haloxyfopPmethyl, it is characterized in that described method carries out as follows:
The reaction of (1) 2,3-two chloro-5-5-flumethiazines and Resorcinol is at K
2CO
3Exist down, at N, carry out nucleophilic substitution reaction in 105～110 ℃ in the dinethylformamide solvent, the described amount of substance ratio that feeds intake is: 2, and 3-two chloro-5-5-flumethiazines: Resorcinol: K
2CO
3It is 1: 2.1: 2.1, N, the consumption of dinethylformamide is with 2,3-two chloro-5-5-flumethiazines are counted every gram 13ml, react end in 4 hours, carry out separation and purification: reclaim solvent N, dinethylformamide, remaining dope water dissolution, it is 1～2 that the following dripping hydrochloric acid aqueous solution of stirring makes the pH value, gained solution extracts with toluene, the saturated common salt water washing of toluene extraction liquid is used anhydrous sodium sulfate drying, concentrating under reduced pressure toluene with gac again after 60 ℃ of decolourings, the gained viscous fluid dissolves with the sherwood oil reflux, and separating out white or light red solid after the cooling is 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine;
(2) 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine with (L)-2-mesyloxy methyl propionate is at K
2CO
3For alkali exists down, in chlorobenzene solvent, carry out nucleophilic substitution reaction in 80～85 ℃, the described amount of substance ratio that feeds intake is: 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine: (L)-2-mesyloxy methyl propionate: K
2CO
3Be 1: 2: 1.5, the chlorobenzene consumption is counted every gram 8ml with 3-chloro-2-(4-hydroxyphenoxy)-5-5-flumethiazine, reacts end in 48 hours, carry out aftertreatment: reaction solution adds entry, be warming up to 60 ℃, stir 30min, abandon water, organic phase washes with water, anhydrous sodium sulfate drying, decompression and solvent recovery, raffinate underpressure distillation, collect 198～201 ℃/1mmHg cut, get colourless being and have the high-optical-purity haloxyfopPmethyl to light yellow oil.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104529838A (en) * | 2014-11-29 | 2015-04-22 | 南京红太阳生物化学有限责任公司 | Synthetic method of haloxyfop intermediate |
| CN104744352A (en) * | 2013-12-25 | 2015-07-01 | 中国中化股份有限公司 | Method for preparing 4-substituted oxyphenol compound |
| CN114213320A (en) * | 2021-12-27 | 2022-03-22 | 江苏中旗科技股份有限公司 | Preparation method of efficient haloxyfop-methyl |
| CN115141139A (en) * | 2022-07-06 | 2022-10-04 | 山东昆达生物科技有限公司 | Method for preparing pentachloropyridine by liquid-phase catalytic chlorination |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4532328A (en) * | 1983-07-14 | 1985-07-30 | The Dow Chemical Company | Process for making optically active esters of phenoxyphenoxypropionic acids or pyridyloxyphenoxypropionic acids |
| CH679396A5 (en) * | 1986-06-12 | 1992-02-14 | Ciba Geigy Ag | |
| US4897481A (en) * | 1988-05-31 | 1990-01-30 | The Dow Chemical Company | Process for the minimization of racemization in the preparation of optically active ((aryloxy)phenoxy)propionate herbicides |
| US5068336A (en) * | 1989-02-27 | 1991-11-26 | Tosoh Corporation | Process for producing 2-(4'-hydroxphenoxy)-3-chloro-5-trifluoromethylpyridine |
| KR100552133B1 (en) * | 2002-06-26 | 2006-02-14 | 한국화학연구원 | A process for R-Aryloxypropionic acid ester derivatives |
| GB0322917D0 (en) * | 2003-09-30 | 2003-11-05 | Syngenta Ltd | Chemical process |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104744352A (en) * | 2013-12-25 | 2015-07-01 | 中国中化股份有限公司 | Method for preparing 4-substituted oxyphenol compound |
| CN104744352B (en) * | 2013-12-25 | 2017-08-04 | 沈阳中化农药化工研发有限公司 | A kind of method for preparing 4 substituted oxy phenol compounds |
| CN104529838A (en) * | 2014-11-29 | 2015-04-22 | 南京红太阳生物化学有限责任公司 | Synthetic method of haloxyfop intermediate |
| CN114213320A (en) * | 2021-12-27 | 2022-03-22 | 江苏中旗科技股份有限公司 | Preparation method of efficient haloxyfop-methyl |
| CN115141139A (en) * | 2022-07-06 | 2022-10-04 | 山东昆达生物科技有限公司 | Method for preparing pentachloropyridine by liquid-phase catalytic chlorination |
| CN115141139B (en) * | 2022-07-06 | 2024-04-02 | 山东昆达生物科技有限公司 | Method for preparing pentachloropyridine by liquid phase catalytic chlorination |
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