WO2009017239A2 - Process for producing toluidine compound - Google Patents
Process for producing toluidine compound Download PDFInfo
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- WO2009017239A2 WO2009017239A2 PCT/JP2008/063929 JP2008063929W WO2009017239A2 WO 2009017239 A2 WO2009017239 A2 WO 2009017239A2 JP 2008063929 W JP2008063929 W JP 2008063929W WO 2009017239 A2 WO2009017239 A2 WO 2009017239A2
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- drying
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- 238000000034 method Methods 0.000 title claims abstract description 52
- -1 toluidine compound Chemical class 0.000 title description 4
- 239000002904 solvent Substances 0.000 claims abstract description 38
- UZCGKGPEKUCDTF-UHFFFAOYSA-N Fluazinam Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=C(Cl)C([N+]([O-])=O)=C1NC1=NC=C(C(F)(F)F)C=C1Cl UZCGKGPEKUCDTF-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000003513 alkali Substances 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 19
- 150000003509 tertiary alcohols Chemical class 0.000 claims abstract description 9
- 230000003472 neutralizing Effects 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 111
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 55
- 239000000047 product Substances 0.000 claims description 43
- WXNPZQIRDCDLJD-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=C(C(F)(F)F)C=C1Cl WXNPZQIRDCDLJD-UHFFFAOYSA-N 0.000 claims description 24
- 238000001035 drying Methods 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 23
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- 239000007864 aqueous solution Substances 0.000 claims description 18
- DPQYRXNRGNLPFC-UHFFFAOYSA-N 2,4-dichloro-1,3-dinitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=C(Cl)C([N+]([O-])=O)=C1Cl DPQYRXNRGNLPFC-UHFFFAOYSA-N 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- DKGAVHZHDRPRBM-UHFFFAOYSA-N t-BuOH Chemical group CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 13
- 239000007795 chemical reaction product Substances 0.000 claims description 11
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 230000000875 corresponding Effects 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 150000004679 hydroxides Chemical class 0.000 claims description 3
- 239000000356 contaminant Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 48
- 239000011541 reaction mixture Substances 0.000 abstract description 14
- 239000005780 Fluazinam Substances 0.000 abstract description 7
- 239000000575 pesticide Substances 0.000 abstract description 6
- 239000004480 active ingredient Substances 0.000 abstract description 5
- 239000012535 impurity Substances 0.000 description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000007792 addition Methods 0.000 description 5
- 230000005591 charge neutralization Effects 0.000 description 5
- 230000001264 neutralization Effects 0.000 description 5
- 238000006386 neutralization reaction Methods 0.000 description 5
- 235000012970 cakes Nutrition 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L Calcium hydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000000920 calcium hydroxide Substances 0.000 description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JTZSFNHHVULOGJ-UHFFFAOYSA-N 3-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CN=C1 JTZSFNHHVULOGJ-UHFFFAOYSA-N 0.000 description 1
- 229960003563 Calcium Carbonate Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L Magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L Magnesium hydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M Potassium bicarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N Sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N Tert-Amyl alcohol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000240 adjuvant Effects 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229940095643 calcium hydroxide Drugs 0.000 description 1
- FBEDQOZZWWECAJ-UHFFFAOYSA-M calcium;magnesium;hydroxide Chemical compound [OH-].[Mg+2].[Ca+2] FBEDQOZZWWECAJ-UHFFFAOYSA-M 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 239000011776 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229960001708 magnesium carbonate Drugs 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 229960000816 magnesium hydroxide Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000001184 potassium carbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001187 sodium carbonate Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Abstract
Because fluazinam is excellent as an active ingredient of pesticides and highly useful, it is desired to produce it efficiently in a proper form with simple operations at low cost in an environmentally friendly manner. The desired product is obtained in good yields with simple operations by using industrially advantageous reaction systems by a process comprising (1) a step of reacting ACTF and DCDNBTF in the presence of an alkali component and a tertiary alcohol as a solvent and (2) a step of neutralizing or acidifying the reaction mixture with an acid.
Description
DESCRIPTION
PROCESS FOR PRODUCING TOLUIDINE COMPOUND
BACKGROUND OF THE INVENTION
TECHNICAL FIELD
The present invention relates to a process for producing 3-chloro-N- (3-chloro-5-trifluoromethyl-2- pyridyl) -a, α, oc-trifluoro-2 , 6-dinitro-p-toluidine as an active ingredient of pesticides (common name: fluazinam) .
BACKGROUND ART
USP 4,331,670 (Patent Document 1) discloses a process for producing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine which comprises reacting 2-amino-3-chloro~5- trifluoromethylpyridine and 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride in the presence of a base and a solvent and discloses alkali metal hydroxides, carbonates and hydrides or alkaline earth metal hydroxides and carbonates as examples of the base and aprotic polar solvents such as dimethylformamide, dimethyl sulfoxide, tetrahydrofuran (THF) , sulfolane and dioxane as examples of the solvent . WO 2007/060662 (Patent Document 2) discloses the use of methyl isobutyl ketone (MIBK) as the solvent in the above-mentioned process disclosed in USP 4,331,670
(Patent Document 1) . Patent Document 2 discloses that a higher yield is attained when the presence of water, which is hardly miscible with MIBK, in the reaction is minimized to decrease the hydrolysis by-product and that the presence of a high concentration of water resulting from the reaction or attributed to the reagents increases the hydrolysis by-product and thereby decreases the yield. Patent Document 2 also discloses that the ratio of the solvent to the reactant should be larger than about 10%w/v and that the solvent is preferably pure MIBK (for example, with a purity of about 98%) or recycled MIBK with a water content of less than 2%, and that in the production of fluazinam as the desired product described in Example 2, the reaction was carried out by adding solid KOH (3.5 mol eq.) to a mixture of 2-amino-3- chloro-5-trifluoromethylpyridine, 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride and a MIBK azeotrope containing 1.6% water.
Patent Document 1: USP 4,331,670 Patent Document 2: WO 2007/060662
DISCLOSURE OF THE INVENTION
Because fluazinam is excellent as an active ingredient of pesticides and highly useful, it is desired to produce fluazinam efficiently in a proper form with simple operations at low cost in an environmentally friendly manner. Especially, there is a demand for
processes preferable from the viewpoints of the cost for industrial production, simplicity of reaction procedures and safety.
Through their extensive research on the reaction conditions and reaction procedures for more efficient and industrially advantageous production of 3-chloro-N- (3- chloro-5-trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6- dinitro-p-toluidine, the present inventors found that the use of a tertiary alcohol such as tertiary butyl alcohol, optionally with the intentional use of a substantial amount of water, carries various advantages and allows a high yield of the desired product, leads to an excellent reaction yield and is favorable for post-reaction operations such as isolation, purification and recovery of the product and accomplished the present invention on the basis of these discoveries.
Namely, the present invention provides the following. [1] A process for producing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine, which comprises (1) a step of reacting 2- amino-3-chloro-5-trifluoromethylpyridine and 2,4- dichloro-3, 5-dinitrobenzotrifluoride in the presence of an alkali component selected from the group consisting of hydroxides and carbonates of alkali metals and hydroxides and carbonates of alkaline earth metals as a basic substance and a tertiary alcohol as a solvent, and (2) a
step of neutralizing or acidifying a mixture containing
3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α,α,α- trifluoro-2 , 6-dinitro-p-toluidine as the reaction product and the solvent with an acid. [2] The process according to [1] , wherein the basic substance is sodium hydroxide or potassium hydroxide.
[3] The process according to [1] or [2] , wherein the solvent is tertiary butyl alcohol.
[4] The process according to any one of [1] to [3] , wherein the acid is hydrochloric acid.
[5] The process according to any one of [1] to [3] , wherein the acid is sulfuric acid.
[6] The process according to any one of [1] to [5] , wherein in the step (1) , water is present in a sufficient amount to substantially dissolve the alkali component.
[7] The process according to any one of [1] to [6] , wherein in the step (1), a 35-50% sodium hydroxide aqueous solution or a corresponding amount of a mixture of a sodium hydroxide aqueous solution, solid sodium hydroxide and water is present in an amount of at least 2 mol, preferably 6 to 10 mol , in relation to 1 mol of 2- amino-3-chloro-5-trifluoromethylpyridine.
[8] The process according to any one of [1] to [7] , wherein in the step (1) , water is present in an amount of at least 7%, preferably 14.8 to 79%, particularly preferably 20 to 40%, in relation to the total of water and the solvent .
[9] The process according to any one of [1] to [8] , wherein in the step (1), 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride is used in an amount of from 0.8 to 1.2 mol, preferably 1 to 1.05 mol , in relation to 1 mol of 2-amino-3-chloro-5-trifluoromethylpyridine . [10] The process according to any one of [1] to [9] , wherein the solvent is used in an amount of from 50 to 1000 g, preferably 100 to 700 g, in relation to 100 g of 2 -amino-3-chloro-5 -trifluoromethylpyridine . [11] The process according to any one of [1] to [5] , wherein in the step (2) , the mixture containing 3-chloro- N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α, α, α-trifluoro- 2 , 6-dinitro-p-toluidine as the reaction product and the solvent is separated, and the organic phase is neutralized or acidified with the acid.
[12] The process according to any one of [1] to [5] and [11] , wherein in the step (2) , the pH is adjusted to 2 to 7, preferably 5 to G, with the acid.
[13] The process according to any one of [1] to [5] , [11] and [12] , wherein in the step (2) , the mixture containing 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α,α,α- trifluoro-2 , 6-dinitro-p-toluidine as the reaction product and the solvent is mixed with water and then neutralized or acidified with the acid to precipitate crystals of the product.
[14] The process according to any one of [1] to [5] and [11] to [13] , wherein in the step (2) , the crystals are
precipitated in the presence of α-crystals of the reaction product as a seed.
[15] A method for purifying 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine as a product, which comprises washing precipitated crystals with hydrous isopropanol to obtain the product in a purer form with less contaminants. [16] The method according to [15] , wherein the precipitated crystals are washed with water before they are washed with hydrous isopropanol.
[17] A method for drying a product, which comprises drying 3-chloro-N- (3 -chloro-5-trifluoromethyl-2-pyridyl) - α, α, α-trifluoro-2 , 6-dinitro-p-toluidine as a product under a reduced pressure. [18] The method for drying a product according to [17] , wherein the drying is carried out under a reduced pressure of at most 300 mmHg.
[19] The method for drying a product according to [17] , wherein the drying is carried out under a reduced pressure of at most 200 mmHg.
[20] The method for drying a product according to any one of [17] to [19] , wherein the drying is carried out at a temperature of 115°C or below.
[21] The method for drying a product according to any one of [17] to [19] , wherein the drying is carried out at a temperature of 700C or below. [22] A process for producing 3-chloro-N- (3-chloro-5-
trifluoromethyl-2 -pyridyl) -α, a, α-trifluoro-2 , 6-dinitro-p- toluidine or a salt thereof, which comprises reacting 2- amino-3-chloro-5-trifluoromethylpyridine and 2,4- dichloro-3 , 5-dinitrobenzotrifluoride in the presence of an alkali component selected from the group consisting of sodium hydroxide and potassium hydroxide and a tertiary alcohol as a solvent .
According to the present invention, in production of 3-chloro-N- (3-chloro-5-trifluoromethyl-2 -pyridyl) -α,α,α- trifluoro-2 , 6-dinitro-p-toluidine by reacting 2-amino-3- chloro-5 -trifluoromethylpyridine and 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride, it is possible not only to obtain the desired product in excellent yields by using industrially advantageous reaction systems through simple procedures, but also to isolate and purify the desired product efficiently and industrially advantageously. The process of the present invention gives a high yield of the desired product and is therefore advantageous over conventional processes in industrial applicability. Further, it is an extremely excellent industrial process from the viewpoints of cost, operations and safety.
Other objects, features, advantages and aspects of the present invention would be clear to a person skilled in the art from the following description. However, it should be understood that the following description and specific examples in the present specification illustrate preferable embodiments of the present invention just for
the sake of explanation. From the teachings of the following description and the rest of the present specification, a person skilled in the art would readily understand various possible changes and/or revisions (modifications) within the intention in the present invention and the scope of the present invention disclosed in the present specification. All the patent documents and reference documents referred to in the present specification are referred to for the sake of explanation, and their contents should be understood to be incorporated in the present specification as part of the present specification.
BEST MODE FOR CARRYING OUT THE INVENTION It is necessary to carry out the above-mentioned step (1) at a sufficient alkali concentration, preferably at the highest possible alkali concentration or under high alkali conditions. As the basic substance, alkali components such as hydroxides and carbonates of alkali metals, hydroxides and carbonates of alkaline earth metals may be mentioned, and specifically, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, calcium hydroxide, magnesium hydroxide, calcium carbonate and magnesium carbonate may be mentioned. Sodium hydroxide, potassium hydroxide, calcium hydroxide and magnesium hydroxide are preferably
mentioned. An alkali selected from the group consisting of sodium hydroxide and potassium hydroxide is preferred for industrial use. Sodium hydroxide is particularly preferred because it is industrially available at low prices. For simplicity, the present invention will be described in reference to sodium hydroxide as a typical example of the basic substance, although other basic substances may be used instead of sodium hydroxide.
In the step (1) , the alkali component may be present in an amount of at least 5 g in relation to 100 g of a tertiary alcohol, although there are no particular restrictions. For example, at least 5 g, preferably at least 8 g, particularly preferably at least 10 g, of sodium hydroxide may be present in the reaction system in relation to 100 g of a tertiary butyl alcohol. In typical cases, the reaction system contains from 10 to 50 g, preferably from 12 to 30 g, particularly preferably from 13 to 20 g, of an alkali such as sodium hydroxide, in relation to 100 g of tertiary butyl alcohol as the solvent.
In the step (1) , it is possible and preferred to incorporate water in an amount enough to substantially dissolve the alkali. In the step (1), at least 2 mol, preferably from 6 to 10 mol, of an alkali component, for example, at least 2 mol, preferably from 6 to 10 mol, of a 30-50% sodium hydroxide aqueous solution, or the corresponding amounts of an alkali such as sodium
hydroxide and water, may be present in the reaction system in relation to 1 mol of 2-amino-3-chloro-5- trifluoromethylpyridine . The concentration of the alkali aqueous solution such as the above-mentioned sodium hydroxide aqueous solution in the reaction solution is preferably from 35 to 50%, particularly preferably from 37 to 48%. The aqueous solution or the corresponding amounts of an alkali such as sodium hydroxide and water may be incorporated into the reaction system by using an alkali aqueous solution such as a sodium hydroxide aqueous solution preliminarily prepared at a predetermined concentration, of course. When a material containing water such as a recycled solvent is used for the reaction, a solid alkali such as sodium hydroxide and water may be used by allowing for the water in the material so that the above-mentioned aqueous solution is obtained in the reactor, and the present invention covers such a case. For example, the concentration of an alkali aqueous solution such as a sodium hydroxide aqueous solution in the reaction system may be raised as long as an alkali such as sodium hydroxide does not remain in the crystalline or solid form in the reaction system at the time of isolation of the desired product.
In the step (1) , although the reaction may be carried out without water in the reaction system, the reaction is carried out preferably in a reaction system containing a substantial amount of water. The
substantial amount of water contained in the reaction system means an amount sufficient not to leave the alkali such as sodium hydroxide in the crystalline or solid form so that the alkali does not have to be separated by solid-liquid separation such as filtration or dissolved by adding water when the desired . product is isolated after the reaction. For example, at least 7%, preferably from 14.8 to 79%, of water may be present in relation to the total of water and the solvent, and typically, from 20 to 40%, of water is present.
In the step (1), from 0.8 to 1.2 mol of 2,4- dichloro-3 , 5-dinitrobenzotrifluoride may be used in relation to 1 mol of 2-amino-3-chloro-5- trifluoromethylpyridine . Preferably, from 1 to 1.05 mol of 2 , 4-dichloro-3 , 5-dinitrobenzotrifluoride may be used in relation to 1 mol of 2-amino-3-chloro-5- trifluoromethylpyridine . The reaction (1) is a condensation reaction between 2-amino-3-chloro-5- trifluoromethylpyridine and 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride, and the two starting materials are preferably used in a ratio within the above-mentioned range by allowing for slight loss of the latter, though they are used in equimolar amounts in theory. Nevertheless, their ratio may fall outside the above- mentioned range.
In the step (1) , from 50 to 1000 g, preferably from 100 to 700 g, of a solvent may be used in relation to 100
g of 2-amino-3-chloro-5-trifluoromethylpyridine . The solvent used in the process of the present invention is selected from tertiary alcohols (such as tertiary butyl alcohol and tertiary amyl alcohol) . The use of such a solvent is not only suitable for attaining a higher yield in the reaction (1) but also greatly simplifies the operations up to recovery of the desired product in the process of the present invention. Such a solvent is miscible with water or forms a low-boiling azeotrope with water.
The reaction procedure in the step (1) such as the order in which the starting materials and the solvent are fed into the reactor is determined considering that the reaction is exothermic and that 2 , 4-dichloro-3 , 5- dinitrobenzotrifluoride is susceptible to hydrolysis.
The best procedure comprises firstly feeding 2-amino-3- chloro-5 -trifluoromethylpyridine and a given amount of a solvent into the reactor, mixing them, then feeding an alkali aqueous solution such as a sodium hydroxide aqueous solution and/or an alkali such as solid sodium hydroxide, if necessary further adding a solvent and/or water for adjustment of the basicity of the resulting solution, mixing the resulting solution, cooling the resulting mixture to 5-30°C for a while and feeding 2,4- dichloro-3 , 5-dinitrobenzotrifluoride dissolved in the solvent. The procedure may be appropriately modified in view of the prices of the starting reaction materials to
be used and the reaction conditions.
The reaction temperature for the reaction is from 10 to 400C, preferably from 15 to 350C. The reaction time is about from 0.5 to 5 hours, preferably about from 1.0 to 3.5 hours. The reaction may be carried out under an atmosphere of an inert gas such as nitrogen or argon. The progress and completion of the reaction can be monitored by instrumental analysis such as HPLC. After completion of the reaction, the reaction mixture is neutralized or acidified with an acid in order to inactivate the excess base in the reaction mixture and liberate the free reaction product from its salt with an alkali such as sodium.
In the step (2) , an acid is used to neutralize or acidify the reaction mixture obtained after completion of the reaction (1) . The acid is preferably hydrochloric acid or sulfuric acid in view of their industrial availability, though any acid at any concentration may be used as long as it can neutralize or acidify the reaction mixture after completion of the reaction (1) . The acid is used in such an amount that it can neutralize or acidify the reaction mixture. When the acid is used at a high concentration, water may be added to the reactor in advance. For example, in the step (2), the reaction mixture obtained after the step (1) may be adjusted to pH 2-7, preferably pH 5-6.
Further, in the step (2) , the reaction mixture
obtained after the step (1) may be neutralized or acidified directly, or the organic phase separated from the reaction mixture may be neutralized or acidified. In the process of the present invention, because the reaction product is formed in the form of an alkali salt such as a sodium salt and migrates into the organic phase, there is no loss of the product at the time of separation of the reaction mixture after the reaction. Addition of water to the reactor before the separation removes the excess sodium hydroxide or the salt resulting from the reaction such as sodium chloride and is favorably keeps down the volume of the reaction system at the time of the subsequent neutralization or acidification of the organic phase. In the step (2), 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine as the reaction product crystallizes in water upon neutralization or acidification of the mixture containing it and the solvent . The solvent in the step (2) is the same solvent as used in the step (1) . The solvent may be removed by distillation at a temperature of from 10 to 65°C, optionally under reduced pressure. The removed solvent is typically recovered as the water azeotrope and may be recycled in the process of the present invention.
Crystals of the desired product obtained in the present invention such as crystals of 3-chloro-N- (3-
chloro-5-trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2, 6- dinitro-p-toluidine (common name: fluazinam) are a known compound disclosed in The Pesticide Manual Thirteenth Edition and the like and are light yellow crystals having a melting point of 115-117°C, called α-crystals. A different form of crystals having a lower melting point is called β-crystals. Stable production of α-crystals is demanded from the viewpoint of manufacturing control .
In the step (2), crystallization may be carried out in the presence of α-crystals of the product as a seed.
The crystals precipitated in water in the step (2) can be recovered easily by ordinary filtration.
The crystals of 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine which precipitate in the step (2) may be purified by washing with hydrous isopropanol . In the purification method by washing, the starting material may preliminarily be washed with water before washed with hydrous isopropanol. The water content of the hydrous isopropanol used for the washing may be appropriately selected so as not to substantially dissolve the desired crystals of 3-chloro-N- (3-chloro-5-trifluoromethyl-2- pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p-toluidine . Isopropanol (IPA) with a low water content unfavorably dissolves the desired crystals of 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine. Typically, at most 90% aqueous isopropanol,
preferably at most 85% aqueous isopropanol, is used. The hydrous isopropanol is used in an amount of from 50 to 500 g, preferably from 100 to 200 g, in relation to 100 g of crystals of the desired product as the starting material .
The results of washing of the crystals of 3-chloro- N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α, α, α-trifluoro- 2 , 6-dinitro-p-toluidine which precipitate in the step (2) with hydrous isopropanol are described below. When the starting crystals (PhOH derivative, 0.25; impurity 1, 0.63; impurity 2, 0.80; other impurities, 2.27; the desired product, 96.05) were washed with 85% aqueous isopropanol, crystals (PhOH derivative, 0; impurity 1, 0; impurity 2, 0; other impurities, 0.74; the desired product, 99.26) were obtained after the washing. The PhOH derivative means a decomposition product of 2,4- dichloro-3, 5-dinitrobenzotrifluoride (DCDNBTF), impurity 1 means 2-amino-3-chloro-5-trifluoromethylpyridine (ACTF) , impurity 2 means DCDNBTF, and the desired product means 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) - α, α, α-trifluoro-2 , 6-dinitro-p-toluidine .
The product, 3-chloro-N- (3-chloro-5-trifluoromethyl- 2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p-toluidine, obtained is suitably dried under a reduced pressure to give a highly pure dry product. In the method for drying a product, optimum conditions can be selected appropriately from conditions which do not cause
decomposition of the desired product, and for example, the drying may be carried out under a reduced pressure of at most 300 mmHg, or a reduced pressure of at most 200 mmHg. In the drying method, the product may be dried, for example, at a temperature of 115°C or below, or at a temperature of 700C or below. The drying method can efficiently provide a stable preparation of the pesticide active ingredient with a good purity.
The crystals thus obtained are formulated with various adjuvants into products in the forms of powders, wettable powders, suspensions.
Now, the present invention will be described in detail with reference to Examples. However, these Examples are mere concrete embodiments for the sake of explanation and by no means limit or restrict the scope of the present invention. It should be understood that the present invention can be carried out in various modes on the basis of the concept in the present specification. All the Examples were carried out or can be carried out by standard techniques common and conventional to a person skilled in the art.
EXAMPLE 1
24.8 g of 2-amino-3-chloro-5-trifluoromethylpyridine (ACTF) (purity 99%, 0.125 mol) and 96 g of tertiary butyl alcohol were fed into a four-necked flask equipped with a stirrer, a thermometer and a dropping funnel and then
mixed with 15.2 g (0.375 mol) of 99% NaOH with stirring.
The resulting mixture was cooled to about 100C, and 40.48 g of 2, 4-dichloro-3 , 5-dinitrobenzotrifluoride (DCDNBTF) powder (purity 98.3%, 0.131 mol) was added while the temperature was kept at 30°C or below. Then, the reaction was carried out at room temperature for about 3 hours .
After addition of 50 g of water, the reaction mixture was neutralized with 15 g of 70% sulfuric acid until the pH reached 5-6 to precipitate crystals. The reaction solution was cooled until the internal temperature reached about 200C or below, and the resulting slurry was filtered under a reduced pressure. The resulting cake was washed with 100 g of water and 80 g of 85% aqueous isopropanol (IPA aq.) . The resulting yellow crystals were dried at 60°C to give 45.58 g of 3- chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α, α, α- trifluoro-2,6-dinitro-p-toluidine (mp . 117-119.5°C) . EXAMPLE 2 24.8 g of ACTF (purity 99%, 0.125 mol) and 106.6 g of tertiary butyl alcohol containing 10% water were fed into a four-necked flask equipped with a stirrer, a thermometer and a dropping funnel and then mixed with 80.6 g of a 48% NaOH aqueous solution and 2.6 g of NaOH flakes (purity 99%) with stirring. The resulting mixture was cooled to about 10°C, and 39.60 g of DCDNBTF powder (purity 99.2%, 0.129 mol) was added while the temperature
was kept at 300C or below. Then, the reaction was carried out at room temperature for about 1 hour.
25 g of water was added to the reaction mixture, and the aqueous phase which separated out as the lower layer was removed. 54 g of water was added to the tertiary butyl alcohol layer, and then 70% sulfuric acid was added dropwise for neutralization until the pH reached 5-6 to precipitate crystals. After addition of 50 g of water, the tertiary butyl alcohol was removed by distillation under reduced pressure (150 mmHg) until the internal temperature reached 600C. The residue was cooled slowly to an internal temperature of about 200C, and the resulting slurry was filtered under a reduced pressure. The resulting cake was washed with 100 g of water and 80 g of 85% IPA aq.. The resulting yellow crystals were dried at 600C to give 45.00 g of 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine . EXAMPLE 3 24.8 g of ACTF (purity 99%, 0.125 mol) and 106.6 g of tertiary butyl alcohol containing 10% water were fed into a four-necked flask equipped with a stirrer, a thermometer and a dropping funnel and mixed with 80.6 g of a 48% NaOH aqueous solution and 2.6 g of NaOH flakes (purity 99%) with stirring. The resulting mixture was cooled to about 200C, and 40.0 g of DCDNBTF powder (purity 98.3%, 0.129 mol) was added while the temperature
was kept at 300C or below. Then, the reaction was carried out at a temperature between 200C and 300C for about 1 hour .
73.7 g of water was added to the reaction mixture, and the aqueous layer which separated out was removed. The tertiary butyl alcohol layer was heated in a warm water bath, and 5% sulfuric acid was gradually added dropwise (about 1.0 mL/min) for neutralization until the pH reached 5-6 to precipitate crystals, while the temperature was kept at 55°C-60°C. When crystals started to precipitate (at pH = about 8), 0.05 g of α-crystals were added as a seed. After the dropwise addition, the crystals were aged at 55°C-60°C for 30 minutes with stirring . The reaction solution was cooled to an internal temperature of 200C or below, and the resulting slurry was filtered under a reduced pressure. The resulting cake was washed with 101.7 g of water and 66.6 g of 85% isopropanol (IPA) aq. The resulting yellow crystals were dried at 600C to give 42.0 g of 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine.
EXAMPLE 4
19.9 g of ACTF (purity 99%, 0.10 mol) and 85.2 g of tertiary butyl alcohol containing 10% water were fed into a four-necked flask equipped with a stirrer, a thermometer and a dropping funnel and mixed with 64.5 g
of a 48% NaOH aqueous solution and 2.1 g of NaOH flakes (purity 99%) with stirring. The resulting mixture was cooled to about 20°C, and 32.0 g of DCDNBTF powder (purity 98.3%, 0.103 mol) was added while the temperature was kept at 300C or below. Then, the reaction was carried out at a temperature between 200C and 300C for about 1 hour .
59.0 g of water was added to the reaction mixture, and the aqueous layer which separated out was removed. 10% sulfuric acid was heated to 600C and mixed with 0.04 g of α-crystals as a seed. The tertiary alcohol layer was gradually added dropwise (about 1.0 mL/min) for neutralization while the temperature was kept at 55°C- 600C until the pH reached 5-6 to precipitate crystals. After the dropwise addition, the crystals were aged at 55°C-60°C for 30 minutes with stirring.
The reaction solution was cooled to an internal temperature of 200C or below, and the resulting slurry was filtered under a reduced pressure. The resulting cake was washed with 81.4 g of water and 53.3 g of 85% isopropanol (IPA) aq. The resulting yellow crystals were dried at 600C to give 34.4 g of 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine .
INDUSTRIAL APPLICABILITY
The present invention makes it possible to
efficiently obtain a highly pure preparation of a pesticide active ingredient, fluazinam, in good yields and in an industrially advantageous manner and makes it possible to isolate and purify the desired product from the reaction system for its synthesis and obtain a dry preparation of the desired product efficiently at low cost with simple operations. Therefore, the process of the present invention is an industrially excellent process . It is clear that the present invention can be practiced in other modes than those described herein or in the Examples. In view of the teachings herein, many revisions and/or variations on the present invention are possible and fall within the scope of the claims attached hereto.
The entire disclosures of Japanese Patent Application No. 2007-202362 filed on August 2, 2007 and Japanese Patent Application No. 2008-037635 filed on February 19, 2008 including specifications, claims and summaries are incorporated herein by reference in their entireties .
Claims
1. A process for producing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine, which comprises (1) a step of reacting 2- amino-S-chloro-B-trifluoromethylpyridine and 2,4- dichloro-3, 5-dinitrobenzotrifluoride in the presence of an alkali component selected from the group consisting of hydroxides and carbonates of alkali metals and hydroxides and carbonates of alkaline earth metals as a basic substance and a tertiary alcohol as a solvent, and (2) a step of neutralizing or acidifying a mixture containing 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α,α,α- trifluoro-2 , 6-dinitro-p-toluidine as the reaction product and the solvent with an acid.
2. The process according to Claim 1, wherein the basic substance is sodium hydroxide or potassium hydroxide.
3. The process according to Claim 1, wherein the solvent is tertiary butyl alcohol.
4. The process according to Claim 1, wherein the acid is hydrochloric acid.
5. The process according to Claim 1, wherein the acid is sulfuric acid.
6. The process according to Claim 1, wherein in the step (1) , water is present in a sufficient amount to substantially dissolve the alkali component.
7. The process according to Claim 1, wherein in the step (1) , a 35-50% sodium hydroxide aqueous solution or a corresponding amount of a mixture of a sodium hydroxide aqueous solution, solid sodium hydroxide and water is present in an amount of at least 2 mol in relation to 1 mol of 2-amino-3-chloro-5-trifluoromethylpyridine .
8. The process according to Claim 1, wherein in the step (1) , water is present in an amount of at least 7% in relation to the total of water and the solvent.
9. The process according to Claim 1, wherein in the step (1), 2,4-dichloro-3 , 5-dinitrobenzotrifluoride is used in an amount of from 0.8 to 1.2 mol in relation to 1 mol of 2-amino-3-chloro-5-trifluoromethylpyridine .
10. The process according to Claim 1, wherein the solvent is used in an amount of from 50 to 1000 g in relation to 100 g of 2-amino-3-chloro-5- trifluoromethylpyridine .
11. The process according to Claim I7 wherein in the step (2), the mixture containing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine as the reaction product and the solvent is separated, and the organic phase is neutralized or acidified with the acid.
12. The process according to Claim 1, wherein in the step (2) , the pH is adjusted to 2 to 7 with the acid.
13. The process according to Claim 1, wherein in the step (2), the mixture containing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine as the reaction product and the solvent is mixed with water and then neutralized or acidified with the acid to precipitate crystals of the product.
14. The process according to Claim 1, wherein in the step (2), the crystals are precipitated in the presence of α- crystals of the reaction product as a seed.
15. A method for purifying 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine as a product, which comprises washing precipitated crystals with hydrous isopropanol to obtain the product in a purer form with less contaminants .
16. The method according to Claim 15, wherein the precipitated crystals are washed with water before they are washed with hydrous isopropanol .
17. A method for drying a product, which comprises drying 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -α,α,α- trifluoro-2 , 6-dinitro-p-toluidine as a product under a reduced pressure.
18. The method for drying a product according to Claim 17, wherein the drying is carried out under a reduced pressure of at most 300 mmHg.
19. The method for drying a product according to Claim 17, wherein the drying is carried out under a reduced pressure of at most 200 mmHg.
20. The method for drying a product according to Claim 17, wherein the drying is carried out at a temperature of
115°C or below.
21. The method for drying a product according to Claim 17, wherein the drying is carried out at a temperature of 700C or below.
22. A process for producing 3-chloro-N- (3-chloro-5- trifluoromethyl-2-pyridyl) -α, α, α-trifluoro-2 , 6-dinitro-p- toluidine or a salt thereof, which comprises reacting 2- amino-3-chloro-5-trifluoromethylpyridine and 2,4- dichloro-3 , 5-dinitrobenzotrifluoride in the presence of an alkali component selected from the group consisting of sodium hydroxide and potassium hydroxide and a tertiary alcohol as a solvent.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007-202362 | 2007-08-02 | ||
| JP2007202362 | 2007-08-02 | ||
| JP2008037635 | 2008-02-19 | ||
| JP2008-037635 | 2008-02-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2009017239A2 true WO2009017239A2 (en) | 2009-02-05 |
| WO2009017239A3 WO2009017239A3 (en) | 2009-06-25 |
Family
ID=40202184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2008/063929 WO2009017239A2 (en) | 2007-08-02 | 2008-07-29 | Process for producing toluidine compound |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP2009221185A (en) |
| AR (1) | AR071540A1 (en) |
| CL (1) | CL2008002276A1 (en) |
| TW (1) | TW200909419A (en) |
| WO (1) | WO2009017239A2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8648203B2 (en) | 2005-11-23 | 2014-02-11 | Makhteshim Chemical Works Ltd. | Process for preparing pyridinamines and novel polymorphs thereof |
| CN106316937A (en) * | 2015-06-29 | 2017-01-11 | 江苏威耳化工有限公司 | Preparation method of fluazinam |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0031257A2 (en) * | 1979-12-25 | 1981-07-01 | Ishihara Sangyo Kaisha Ltd. | Pyridylanilines |
| WO2007060662A2 (en) * | 2005-11-23 | 2007-05-31 | Makhteshim Chemical Works Ltd. | Process for preparing pyridinamines and novel polymorphs thereof |
-
2008
- 2008-07-08 JP JP2008178338A patent/JP2009221185A/en active Pending
- 2008-07-22 TW TW097127806A patent/TW200909419A/en unknown
- 2008-07-29 WO PCT/JP2008/063929 patent/WO2009017239A2/en active Application Filing
- 2008-08-01 AR ARP080103357A patent/AR071540A1/en unknown
- 2008-08-01 CL CL2008002276A patent/CL2008002276A1/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0031257A2 (en) * | 1979-12-25 | 1981-07-01 | Ishihara Sangyo Kaisha Ltd. | Pyridylanilines |
| WO2007060662A2 (en) * | 2005-11-23 | 2007-05-31 | Makhteshim Chemical Works Ltd. | Process for preparing pyridinamines and novel polymorphs thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8648203B2 (en) | 2005-11-23 | 2014-02-11 | Makhteshim Chemical Works Ltd. | Process for preparing pyridinamines and novel polymorphs thereof |
| CN106316937A (en) * | 2015-06-29 | 2017-01-11 | 江苏威耳化工有限公司 | Preparation method of fluazinam |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009221185A (en) | 2009-10-01 |
| WO2009017239A3 (en) | 2009-06-25 |
| CL2008002276A1 (en) | 2009-08-07 |
| AR071540A1 (en) | 2010-06-30 |
| TW200909419A (en) | 2009-03-01 |
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