200909419 九、發明說明 【發明所屬之技術領域】 本發明關於一種製造作爲殺蟲劑（俗名爲氟淨南 (fluazinam))之活性成分的3-氯-N-(3-氯-5-三氟甲基_2-口比 啶基）-〇1，(1,〇1-三氟-2,6-二硝基-對甲苯胺之方法。 【先前技術】 美國專利案號4,3 3 1,670(專利文件1)揭示一種製造3_ 氯- N- (3-氯-5-二氟甲基-2-批Π定基）-α，α，α-三氣- 2,6-二硝基_ 對甲苯胺之方法，其包含於鹼和溶劑之存在下令2 -胺基_ 3 -氯-5 -三氟甲基吡啶與2,4 -二氯-3,5 -二硝基苄川三氟反應 ’且該專利案揭不使用驗金屬氨氧化物、碳酸鹽及氯化物 或鹼土金屬氫氧化物和碳酸鹽作爲該鹼之實例並使用非質 子之極性溶劑（諸如二甲基甲醯胺、二甲亞颯、四氫呋喃 (THF)、環丁颯及二噁烷）作爲該溶劑之實例。 PCT專利案WO 2007/060662(專利文件2)揭示於上述 美國專利案號4,33 1,670(專利文件1)所揭示之方法中使用 甲基異丁基甲酮（MIBK)作爲溶劑。專利文件2揭示當使反 應中存在之與MIBK幾乎不互溶的水最少以減少副產物之 水解時能得到較高之產率，且存在自該反應所產生或因反 應劑所產生之高量的水會增加副產物之水解並因而降低產 率。專利文件2亦揭示溶劑對反應物之比例應大於約 1 0%w/v，該溶劑較佳地係純MIBK(例如約98%純度）或含 水量低於2 %之再循環的ΜIB K，且於其實施例2所述之製 200909419 造氟淨南作爲所欲之產物中，藉由將κο Η固體（3.5莫耳 當量）加入至2 -胺基-3-氯-5-三氟甲基吡啶、2,4 -二氯- 3,5-二硝基苄川三氟及含有1.6%水之ΜΙΒΚ的共沸混合物之混 合物中以進行該反應。 專利文件1 :美國專利案號4,33 1,670 專利文件2 : PCT專利案WO 2007/060662 【發明內容】 因氟淨南作爲殺蟲劑之活性成分係優異且具有高度利 用性的，所欲的係於對環境友善之方式、低成本及簡單操 作下有效地製造呈適當形式之氟淨南。特定地，需要較佳 地自工業量產成本、反應程序簡化及安全考量之製造方法 〇 藉由對3-氯-Ν-(3-氯_5·三氟甲基-2-吡啶基）-α，α，α-三 氟-2,6-二硝基-對甲苯胺之較具效率和產業優異性的製造 方法之反應條件和反應程序作廣泛之硏究，本案之發明人 發現使用叔醇（諸如特丁醇）且可選擇地欲倂用實際存在之 水能提供許多不同之優點、能產生高產率之所欲產物並導 致優異之反應產率，且有益於反應後之操作（諸如產物之 分離、純化及回收），並基於該等發現而完成本發明。 即，本發明提供下述： [1] 一種製造3 -氯-Ν-(3-氯-5 -三氟甲基-2-吡啶基）-〇[，〇1,(1-三氧-2,6 - 一硝基彳甲本fe之方法’其包含（1)於& 自鹼金屬之氫氧化物和碳酸鹽或鹼土金屬之氫氧化物和碳 -6- 200909419 酸鹽作爲鹼性物質的鹼成分和作爲溶劑的叔醇之存在下令 2_胺基-3-氯-5-三氟甲基吡啶與2,4_二氯-3,5-二硝基苄川 三氟反應之步驟’及（2)利用酸使含有作爲反應產物之3_ 氯·Ν-(3 -氯-5-三氟甲基-2-吡啶基）-α,α，α-三氟-2,6-二硝基-對甲苯胺和該溶劑的混合物中和或酸化之步驟。 [2 ]如該[1 ]之方法’其中該鹼性物質係氫氧化鈉或氫 氧化鉀。 [3 ]如該[1 ]或[2 ]之方法，其中該溶劑係特丁醇。 [4] 如該[1]至[3]中任一之方法，其中該酸係氫氯酸。 [5] 如該[1]至[3]中任一之方法，其中該酸係硫酸。 [6] 如該[1]至[5]中任一之方法，其中於該步驟（1)中水 之存在量係足以實質上溶解該鹼成分。 [7] 如該[1]至[6]中任一之方法，其中於該步驟（1)中存 在相對於1莫耳之2-胺基-3-氯-5-三氟甲基吡啶爲至少2莫 耳（較佳地6至10莫耳）之3 5至50%氫氧化鈉水溶液或相對量 之氫氧化鈉水溶液、氫氧化鈉固體及水的混合物。 [8] 如該[1]至[7]中任一之方法，其中於該步驟（1)中存 在相對於水與該溶劑之總量至少爲7 % (較佳地1 4.8至7 9 % 且特佳地20至40%)之水。 [9 ]如該[1 ]至[8 ]中任一之方法，其中於該步驟（1)中使 用相對於1莫耳之2-胺基-3-氯-5-三氟甲基吡啶爲0.8至1.2 莫耳（較佳地1至1·〇5莫耳）之2,4-二氯-3,5-二硝基苄川三氟 [10]如該Π]至[9]中任一之方法，其中該溶劑之用量 200909419 相對於100 g之2-胺基.3-氯-5-三氟甲基吡啶爲50至1000 g(較佳地1 〇〇至700 g)。 [U]如該[1]至[5]中任一之方法，其中於該步驟（2)中 令該含有作爲反應產物之3-氯-N-(3-氯-5-三氟甲基-2_吡 啶基）-α,α,α-三氟-2,6-二硝基-對甲苯胺的混合物與溶劑分 離並令有機相經酸中和或酸化。 [12] 如該[1]至[5]及[11]中任一之方法，其中於該步驟 (2)中pH係經酸調整爲2至7(較佳地5至6)。 [13] 如該[1]至[5]、[11]及[12]中任一之方法，其中於 該步驟（2)中令該含有作爲反應產物之3-氯-N-(3-氯-5-三 氟甲基一-吡啶基卜^心三氟一^-二硝基-對甲苯胺和溶 劑的混合物與水混合並隨後經酸中和或酸化以沉澱該產物 之結晶。 [14] 如該[1]至[5]及[11]至[I3]中任一之方法，其中於 該步驟（2)中係於作爲晶種之該反應產物的α -結晶之存在 下使該結晶沉澱。 [15] —種純化作爲產物的3 -氯-Ν-(3 -氯-5-三氟甲基- 2- 吡啶基）-α，α,α-三氟_2,6_二硝基-對甲苯胺之方法，其包含 令沉澱之結晶經含水之異丙醇沖洗以得到含有較少污染物 呈較純型式之產物。 _ [16] 如該[15]之方法，其中該沉澱之結晶於經含水之 異丙醇沖洗之前係經水沖洗。 [17] —種乾燥產物之方法，其包含於減壓下乾燥作爲 產物之3-氯-Ν-(3-氯-5·三氟甲基-2-吡啶基）-α，α，α-三氟- 200909419 2,6-二硝基-對甲苯胺。 [18] 如該[17]之乾燥產物之方法，其中係於至多300 mmHg之減壓下實施該乾燥。 [19] 如該[17]之乾燥產物之方法，其中係於至多200 mmHg之減壓下實施該乾燥。 [20] 如該[17]至[19]中任一之乾燥產物之方法，其中 係於1 1 5 °C或低於1 1 5 °C之溫度下實施該乾燥。 [2 1]如該[17]至[19]中任一之乾燥產物之方法，其中 係於70°C或低於7(TC之溫度下實施該乾燥。 [2 2] —種製造3-氯-N-(3-氯-5-三氟甲基-2-吡啶基）-α，α,α-三氟-2,6-二硝基-對甲苯胺或其鹽之方法，其包含於 選自氫氧化鈉或氫氧化鉀之鹼成分和作爲溶劑的叔醇之存 在下令2-胺基-3-氯-5-三氟甲基吡啶與2,4-二氯-3,5-二硝 基苄川三氟反應。 依據本發明，於藉由令2-胺基-3-氯-5-三氟甲基吡啶 與2,4-二氯-3,5-二硝基苄川三氟反應以製造3-氯-N-(3-氯-5-三氟甲基·2-吡啶基）-α，α，α-三氟-2,6-二硝基·對甲苯胺之 方法中，不僅可透過簡單之製程並藉由使用產業上有利之 反應系統以得到具有優異產率之所欲產物，亦可有效地且 產業上有利地分離並純化該所欲產物。本發明之方法提供 高產率之所欲產物，因此較慣用之方法更具有產業上可利 用性。再者，自成本、操作性及安全性考量，本發明之方 法係極爲優異之產業方法。 熟習此技藝之人士自下述之說明當能清楚明瞭本發明 -9- 200909419 之其他目標、特徵、優點及面向。然而，應當瞭解的是本 說明書之下述說明及特定實例僅係爲了解說目的而闡釋本 發明之較佳體系。自下述說明及本說明書之其餘部分的教 示可知，熟習此技藝之人士當能易於瞭解在本發明之內容 和本說明書所揭示的本發明之範圍內存有各種不同可能之 變化及/或修改（修飾）。本說明書所引述之所有專利文件和 參考文件係供說明，且應瞭解的是彼等之內容係倂入本說 明書中成爲本說明書之一部分。 實施本發明之最佳模式 必須於足夠之鹼濃度（較佳地最高可能之鹼濃度或高 鹼條件）下實施上述之步驟（1)。可提及的作爲鹼性材料之 鹼成分係諸如鹼金屬之氫氧化物和碳酸鹽及鹼土金屬之氫 氧化物和碳酸鹽，且特別地係氫氧化鈉、氫氧化鉀、碳酸 鈉、碳酸鉀、碳酸氫鈉、碳酸氫鉀、氫氧化鈣、氫氧化鎂 、碳酸鈣及碳酸鎂。較佳地，可提及的是氫氧化鈉、氫氧 化鉀、氫氧化鈣及氫氧化鎂。選自氫氧化鈉或氫氧化鉀之 鹼係較適宜地供產業上使用。氫氧化鈉係特別適宜的，因 其可以低價格自產業上購得。雖然可使用其他鹼性物質以 替代氫氧化鈉，但是爲簡單起見，本發明將描述使用氫氧 化鈉作爲該鹼性物質之典型實例。 於該步驟（1)中，雖然無特別限制，但是該鹼成分量 可爲至少5 g/1 〇 〇 g叔醇。例如，相對於1 0 0 g特丁醇，該 反應系統中可存有至少5 g(較佳地至少8 g且特佳地至少 -10- 200909419 10 g)之氫氧化鈉。典型上，相對於100 g作爲溶劑之特丁 醇，該反應系統含有10至50 g(較佳地12至30 g且特佳地 13至20 g)之鹼（諸如氫氧化鈉）。 於該步驟（1)中，加入足以實質上溶解該鹼之水量係 可行且適宜的。於該步驟（υ中，相對於1莫耳之2-胺基-3· 氯-5-三氟甲基吡啶，該反應系統中可存有至少2莫耳（較 佳地6至10莫耳）之鹼成分（例如至少2莫耳（較佳地6至10莫 耳）之30至50%氫氧化鈉水溶液或對應量之鹼（諸如氫氧化 鈉）和水）。反應溶液中該鹼水溶液（諸如上述之氫氧化鈉 水溶液）之濃度較佳地係35至50%(特佳地係37至48%)。當 然，藉由使用經預先製備且具有預定濃度之鹼水溶液（諸 如氫氧化鈉水溶液），可將該水溶液或對應量之鹼（諸如氫 氧化鈉）和水加入至該反應系統中。當含有水之物料（諸如 再循環之溶劑）係用於反應時，因考慮該物料中之水，可 使用固態鹼（諸如氫氧化鈉）和水，使得反應器中存有上述 之水溶液，且本發明含括此一情況。例如，只要反應系統 中之鹼（諸如氫氧化鈉）於分離所欲產物時不爲結晶或固體 型式，可提高該反應系統中之鹼水溶液（諸如氫氧化鈉水 溶液）的濃度。 於該步驟（1)中，雖然於該反應系統中該反應可於無 水之情況下進行，但是該反應較佳地係於實質上含有水之 反應系統中進行。該反應系統實質上含有水係指該水量足 以不致使該鹼（諸如氫氧化鈉）呈結晶或固體型式，使得當 反應後分離所欲產物時，毋須藉由固相/液相分離（諸如過 -11 - 200909419 濾）以分離該鹼或藉由添加水以溶解該鹼。例如，相對於 水與溶劑之總量，水量可爲至少7%(較佳地1 4.8至7 9°/。）， 且典型上存有20至4〇%之水。 於該步驟（1)中，相對於1莫耳之2 -胺基-3 -氯-5 -三氟 甲基吡啶，可使用0.8至1.2莫耳之2,4-二氯-3,5-二硝基苄 川三氟。較佳地，相對於1莫耳之2-胺基-3-氯-5-三氟甲基 吡啶，可使用1至1 .05莫耳之2,4-二氯-3，5-二硝基苄川三 氟。該反應（1)係2-胺基-3-氯-5-三氟甲基吡啶與2,4-二氯-3，5 -二硝基苄川三氟之縮合反應，且雖然理論上使用等莫 耳量之2-胺基-3-氯-5-三氟甲基吡啶與2,4-二氯-3,5-二硝 基苄川三氟，但是因考量2,4-二氯-3,5-二硝基苄川三氟之 些微損失，較佳地該兩種起始物之使用比例係落入上述範 圍內。雖然如此，該比例可爲上述範圍外。 於該步驟（1)中，相對於100 g之2-胺基-3-氯-5-三氟 甲基吡啶，可使用50至1000 g(較佳地100至700 g)之溶劑 。本發明之方法所使用之溶劑係選自叔醇（諸如特丁醇和 特戊醇）。使用該溶劑不僅適於達成反應（1)之較高產率， 亦大大地簡化本發明之方法中達至回收所欲產物之操作。 該溶劑可與水互溶或與水形成低沸點之共沸混合物。 考量該反應係放熱且2,4-二氯-3,5-二硝基苄川三氟易 受水解作用以決定該步驟（1)之反應程序（諸如起始物與溶 劑餵入反應器之次序）。最佳之程序包含首先將2-胺基-3-氯-5 -三氟甲基吡啶和預定量之溶劑餵入至反應器中，進 行混合，隨後餵入鹼水溶液（諸如氫氧化鈉水溶液）及/或鹼 -12- 200909419 (諸如氫氧化鈉固體），如需要地進一步加入溶劑及/或水以 調整所生成之溶液的鹼度，混合所生成之溶液，冷卻所生 成之混合物至5至30°C並餵入溶解於該溶劑中之2,4-二氯_ 3,5 -二硝基苄川三氟。考量欲使用之起始反應物的價格及 反應條件，可適當地修改該程序。 反應溫度係介於至4〇°C (較佳地15至35°C )。反應時 間係約〇 . 5至5小時（較佳地約1 · 〇至3 · 5小時）。該反應可於 惰性氣體（諸如氮氣或氬氣）下進行。藉由儀器分析（諸如 HPLC)可監測該反應之進行及完成。該反應完成後’反應 混合物係經酸中和或酸化以使該反應混合物中過量之鹼失 去作用並利用鹼（諸如鈉）使自由之反應產物自彼之鹽釋出 〇 於該步驟（2)中，利用酸中和或酸化自反應（1)完成後 所得之反應混合物。雖然可使用任何濃度之任何酸（只要 該酸能中和或酸化自反應（υ完成後所得之反應混合物）’ 但是考量產業上可取得性，該酸較佳地係氫氯酸或硫酸。 該酸之用量係能中和或酸化該反應混合物之量。當使用高 濃度之酸時，可預先將水加入至反應器中。例如’於該步 驟（2)中，可將自該步驟（1)後所得之反應混合物的PH調 整爲2至7(較佳地5至6)。 再者，於該步驟（2)中，自該步驟（1)後所得之反應混 合物可直接經中和或酸化，或自該反應混合物分離之有機 相可經中和或酸化。於本發明之方法中，因爲反應產物係 以鹼鹽（諸如鈉鹽）之型式形成並移至有機相’故於反應後 -13- 200909419 分離反應混合物時並無產物損失。於該分離前加入水至反 應器中將除去過量之氫氧化鈉或自該反應所生成之鹽（諸 如氯化鈉）並有利地於隨後中和或酸化有機相時壓低反應 系統之體積。 於該步驟（2)中，含有3-氯-N-(3-氯-5-三氟甲基-2·吡 啶基）-α，α,α-三氟-2,6-二硝基-¾甲苯胺和溶劑之混合物經 中和或酸化時，作爲反應產物之3 -氯-N-(3 -氯-5 -二氟甲 基-2-吡啶基）-〇1，〇1,〇1-三氟-2,6-二硝基-對甲苯胺係於水中 結晶。 該步驟（2)所使用之溶劑係與該步驟（1 )所使用者相同 。該溶劑可於1 〇至65 °C之溫度下且可選擇地於減壓下經蒸 餾除去。被除去之溶劑典型上係以水共沸混合物之型式被 回收且可於本發明之方法中再循環利用。 本發明所得之所欲產物的結晶（諸如3 -氯-N - (3 -氯-5 -三氟甲基-2-吡啶基）-α,α，α-三氟-2,6-二硝基-對甲苯胺（俗 名爲氟淨南）之結晶）係揭示於殺蟲劑手冊（第Π版）及類似 文獻中之習知化合物且係熔點爲Π5-1 17°C之淡黃色結晶（ 稱爲α結晶）。具有較低熔點之不同結晶型係稱爲卩結晶 。考量製造程序控制，需要α結晶之穩定製造方法。 於該步驟（2)中，結晶可於作爲晶種之產物的α結晶 之存在下進行。 於該步驟（2)中，於水中沉澱之結晶可容易地藉由慣 用之過濾方法回收。 該步驟（2)中沉澱之3-氯-Ν-(3-氯-5_三氟甲基-2-吡啶 -14 - 200909419 基）-α，α，α -三氟-2，6 -二硝基-對甲苯胺的結晶可經含水之異 丙醇沖洗而加以純化。於經由沖洗之純化方法中，起始物 於經含水之異丙醇沖洗前可預先經水沖洗。可適當地選擇 該用於沖洗的該含水之異丙醇中的水量，使得不會實質上 溶解所欲的3-氯- Ν-(3-氯-5-三氟甲基-2-吡啶基）-α，α，α-三 氟-2,6-二硝基-對甲苯胺之結晶。含低水量之異丙醇（IPΑ) 不利地溶解所欲的3-氯-N-(3-氯-5-三氟甲基-2-吡啶基）-α，α,α-三氟-2,6-二硝基-對甲苯胺之結晶。典型上’使用至 多9 0 %異丙醇水溶液（較佳地至多8 5 %異丙醇水溶液）。相 對於1 〇〇 g之作爲起始物的所欲產物之結晶，該含水之異 丙醇的用量係5 0至500 g(較佳地100至200 g)。 利用含水之異丙醇沖洗於該步驟（2)中沉澱之3-氯 (3-氯-5-三氟甲基-2-吡啶基）-α,α，α-三氟-2,6-二硝基-對甲 苯胺的結晶之結果係說明如下。當使用85%異丙醇水溶液 沖洗起始結晶（PhOH衍生物，0.25 ;雜質1 ’ 0.63 ;雜質2 ，0.80 ;其他雜質，2.27 ;所欲產物，96.05)時，經沖洗 後得到結晶（PhOH衍生物，0 ;雜質1，0 ;雜質2，0 ;其 他雜質，0.74 ;所欲產物，99.26)。該PhOH衍生物表示 2,4-二氯-3,5-二硝基苄川三氟（DCDNBTF)之分解產物’雜 質1表示2-胺基-3-氯-5-三氟甲基吡啶（ACTF)，雜質2表示 DCDNBTF，且該所欲產物表示3-氯-N-(3-氯-5-三氟甲基-2-吡啶基）-α,α,α-三氟- 2,6-二硝基對甲苯胺。 所得之產物3 -氯-N-(3-氯-5 -三氟甲基-2 -吡啶基）-α,α,α-三氟-2,6-二硝基-對甲苯胺係適當地於減壓下經乾燥 -15- 200909419 以生成高度純化之乾燥產物。於乾燥產物之方法中，可自 不會致使所欲產物分解之條件中適當地選擇最佳條件，且 例如該乾燥可於至多300 mm Hg之減壓下或至多200 mmHg 之減壓下進行。於該乾燥方法中，產物可於例如Π 5 °C或 低於1 1 5 °c之溫度下經乾燥或於70 °c或低於70t之溫度下 經乾燥。該乾燥方法可有效地提供具有良好純度之殺蟲劑 活性成分的安定製劑。 所得到之結晶係與不同之佐劑調製成呈粉末、可潤濕 之粉末或懸浮劑型式之產物。 現今，本發明將參考實施例加以詳細說明。然而，該 等實施例僅係用於說明之具體較佳體系且絕非用於限制或 縮限本發明之範圍。應瞭解的是基於本說明書中之槪念， 可以不同模式實施本發明。 藉由熟習此技藝之人士所公知或慣用之標準技術實施 或可實施所有實施例。 【實施方式】 實施例1 將2 -胺基-3 -氯-5 -三氟甲基吡啶（A c T F ;純度9 9 % , 24.8 g’ 0.125莫耳）和特丁醇（96 g)餵入至配備有攪拌器、 溫度目十及滴液漏斗之四頸燒瓶中並隨後於攪拌下與99% NaOH(15’2 g，0_3 75莫耳）混合。冷卻所生成之混合物至 約l〇°C並於維持於3CTC或低於3(TC之溫度下加入2,4-二氯- 3,5 -一 硝基卞川二氟（DCDNBTF)粉末（純度 98.3%，40.48 g -16- 200909419 ，0.1 3 1莫耳）。隨後令該反應於室溫下進行約3小時。 經加入水（50 g)後，令該反應混合物經70%硫酸（15 g) 中和至pH達5至6以沉澱結晶。冷卻該反應溶液直至內部 溫度達到約20t或低於20°C且於減壓下過濾所生成之漿泥 。令所生成之濾餅經水（100 g)和85%異丙醇水溶液（80 g) 沖洗。令所生成之黃色結晶於60 °C下經乾燥以生成3 -氯-N-(3-氯-5-三氟甲基-2-毗啶基）-α,α，α-三氟-2,6-二硝基·對 甲苯胺（45.5 8 g，mp. 1 17-1 1 9.5Τ )。 實施例2 將ACTF(純度99%，24.8 g，0.125莫耳）和含有10%水 之特丁醇（106.6 g)餵入至配備有攪拌器、溫度計及滴液漏 斗之四頸燒瓶中並隨後於攪拌下與48% NaOH水溶液（80.6 g)和NaOH薄片（2.6 g，純度99%)混合。冷卻所生成之混 合物至約1 0 °C並於維持於30 °C或低於3 0 °C之溫度下加入 DCDNBTF 粉末（純度 99.2%，39.60 g，0.129 莫耳）。隨後 令該反應於室溫下進行約1小時。 將水（25 g)加入至該反應混合物中並除去經分離爲下 層之水相。將水（54 g)加入至該特丁醇層中並隨後逐滴加 入用於中和之70%硫酸直至pH達5至6以沉澱結晶。經加 入水（50 g)後，於減壓（150 mmHg)下藉由蒸餾以除去該特 丁醇直至內部溫度達6 0 °C。緩慢冷卻殘餘物至內部溫度約 2〇°C並於減壓下過濾所生成之漿泥。令所生成之濾餅經水 (100 g)和85%異丙醇水溶液（80 g)沖洗。令所生成之黃色 -17- 200909419 結晶於6(TC下經乾燥以生成3-氯-N-(3-氯-5-三氟甲基-2-吡啶基）-1〇,〇1-三氟-2,6-二硝基-對甲苯胺（45.〇〇§)。 實施例3 將ACTF(純度99%，24.8 g，0.125莫耳）和含有10%水 之特丁醇（106.6 g)餵入至配備有攪拌器、溫度計及滴液漏 斗之四頸燒瓶中並隨後於攪拌下與48% Na〇H水溶液（80.6 g)和NaOH薄片（2.6 g，純度99%)混合。冷卻所生成之混 合物至約2 0 °C並於維持於3 0°C或低於3 0 °C之溫度下加入 DCDNBTF粉末（純度98·3%，40.0g，0·129莫耳）。隨後令 該反應於介於20至3 0°C之溫度下進行約1小時。 將水（73.7 g)加入至該反應混合物中並除去經分離之 水層。令該特丁醇層於溫水洛中加熱並緩慢逐滴（約1 .0 ml/分鐘）加入用於中和之5%硫酸直至pH達5至6以沉澱結 晶（同時將溫度維持介於S 5 °C至60°C )。當結晶開始沉澱時 (於pH約8)，加入作爲晶種之α結晶（〇.〇5 g)。經該逐滴 加入後，該結晶於55°C至60°C且於攪拌下經30分鐘老化。 冷卻該反應溶液至內部溫度約2 0 °C或低於2 0 °C並於減 壓下過濾所生成之漿泥。令所生成之濾餅經水（101.7 g)和 85 %異丙醇水溶液（66.6 g)沖洗。令所生成之黃色結晶於 60°C下經乾燥以生成3-氯- N-(3-氯-5-三氟甲基-2-吡啶基）-(*，〇1，(1-三氟-2,6-二硝基-對甲苯胺（42.0§)。 實施例4 • 18 - 200909419 將ACTF(純度99%，19_9 g ’ 0_10莫耳）和含有10%水 之特丁醇（85.2 g)餵入至配備有攪拌器、溫度計及滴液漏 斗之四頸燒瓶中並隨後於攪拌下與48% NaOH水溶液（64.5 g)和N a Ο Η薄片（2.1 g，純度9 9 %)混合。冷卻所生成之混 合物至約20 °C並於維持於3 0 °C或低於3 (TC之溫度下加入 〇€〇仙丁？粉末（純度98.3%，32.0§，0.103莫耳）。隨後令 該反應於介於2 0至3 (TC之溫度下進行約1小時。 將水（5 9 · 0 g)加入至該反應混合物中並除去經分離之 水層。加熱10%硫酸至60 °C並與作爲晶種之α結晶（〇.〇4 g)混合。將用於中和之該混合液緩慢逐滴（約1.0 ml/分鐘） 加入至該叔醇層中直至P Η達5至6以沉澱結晶（同時將溫度 維持介於55°C至6(TC )。經該逐滴加入後，該結晶於55t 至60 °C且於攪拌下經30分鐘老化。 冷卻該反應溶液至內部溫度約2 CTC或低於2 0 °C並於減 壓下過濾所生成之漿泥。令所生成之濾餅經水（8 1.4 g)和 85%異丙醇水溶液（53.3 g)沖洗。令所生成之黃色結晶於 6〇°C下經乾燥以生成3-氯-N-(3-氯-5-三氟甲基-2-吡啶基）-α，α，α-三氟-2,6-二硝基-對甲苯胺（34.4 g)。 產業上利用性 本發明可有效率地以良好產率和對產業有利之方式得 到殺蟲劑活性成分（氟淨南）之闻純度製劑，可自合成氟淨 南之反應系統分離並純化所欲之產物並可以低成本及簡單 操作之方式有效率地得到該所欲產物之乾燥製劑。因此， -19- 200909419 本發明之方法係產業上優異之方法。 明顯地，可以本說明書或前述實施例所述之模式以外 的其他模式實施本發明。基於本發明之教示，對本發明之 許多修改及/或變化係爲可能且係落入所附之申請專利範 圍的範疇內。 日本專利申請案號2007-202362(於2007年8月2日提出 申請）和日本專利申請案號2008-037635(於2008年2月19日 提出申請）所揭示之全部內容（包括說明書、申請專利範圍 及摘要）係倂入本說明書作爲參考。 -20-200909419 IX. INSTRUCTIONS OF THE INVENTION [Technical Field to Which the Invention Is Along] The present invention relates to a 3-chloro-N-(3-chloro-5-trifluorocarbon) for producing an active ingredient as an insecticide (commonly known as fluazinam) Method for the methyl 2-bromopyridyl)-hydrazine 1, (1, fluorene 1-trifluoro-2,6-dinitro-p-toluidine. [Prior Art] US Patent No. 4,3 3 1,670 (Patent Document 1) discloses a process for producing 3-chloro-N-(3-chloro-5-difluoromethyl-2-benzazepine)-α,α,α-tris- 2,6-dinitro-pair A method of toluidine comprising reacting 2-amino-3-chloro-5-trifluoromethylpyridine with 2,4-dichloro-3,5-dinitrobenzyltrifluoride in the presence of a base and a solvent 'This patent discloses the use of metal oxides, carbonates and chlorides or alkaline earth metal hydroxides and carbonates as examples of such bases and the use of aprotic polar solvents (such as dimethylformamide, II) As an example of the solvent, PCT patent WO 2007/060662 (Patent Document 2) is disclosed in the above-mentioned U.S. Patent No. 4,33 1,670 (Patent Document 1) Used in the disclosed method Methyl isobutyl ketone (MIBK) is used as a solvent. Patent Document 2 discloses that when the water which is almost immiscible with MIBK in the reaction is minimized to reduce the hydrolysis of by-products, a higher yield can be obtained, and there is a reaction from the reaction. The high amount of water produced or produced by the reactants increases the hydrolysis of by-products and thus reduces the yield. Patent Document 2 also discloses that the ratio of solvent to reactant should be greater than about 10% w/v, preferably solvent. A pure MIBK (for example, about 98% purity) or a recycled Μ IB K having a water content of less than 2%, and in the product of the invention described in Example 2, 200909419 fluorinated as a desired product, by κο Hydrazine solid (3.5 mole equivalent) was added to 2-amino-3-chloro-5-trifluoromethylpyridine, 2,4-dichloro-3,5-dinitrobenzyltrifluoride and 1.6% water Then, the reaction is carried out in a mixture of azeotropes. Patent Document 1: U.S. Patent No. 4,33 1,670 Patent Document 2: PCT Patent Publication No. WO 2007/060662 [Disclosed to the Invention] The active ingredient is excellent and highly available, and the desired way is to be environmentally friendly. In this and simple operations, it is effective to produce fluorocarbon in a suitable form. Specifically, a manufacturing method preferably from industrial mass production cost, simplified reaction procedure, and safety considerations is required by 3-chloro-indole-(3) Reaction conditions for a manufacturing method with higher efficiency and industrial superiority of -chloro-5·trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine The reaction process has been extensively studied, and the inventors of the present invention have discovered that the use of tertiary alcohols (such as tert-butyl alcohol) and optionally the use of water that is actually present provides many different advantages and produces high yields of desired products. This results in an excellent reaction yield and is beneficial to the post-reaction operation (such as separation, purification and recovery of the product), and the present invention has been completed based on these findings. That is, the present invention provides the following: [1] A process for producing 3-chloro-indole-(3-chloro-5-trifluoromethyl-2-pyridinyl)-indole [, 〇 1, (1-trioxo-2) , 6 - a method of nitro guanidine, which comprises (1) a hydroxide of a hydroxide of an alkali metal and a carbonate or an alkaline earth metal, and a carbon-6-200909419 acid salt as a basic substance Step of reacting 2-amino-3-chloro-5-trifluoromethylpyridine with 2,4-dichloro-3,5-dinitrobenzyltrifluoride in the presence of an alkali component and a tertiary alcohol as a solvent 'And (2) using an acid to contain 3_chloroindole-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-di as a reaction product A step of neutralizing or acidifying a mixture of nitro-p-toluidine and the solvent. [2] The method of [1] wherein the alkaline substance is sodium hydroxide or potassium hydroxide. [3] as the [1] The method of [2], wherein the solvent is a monobutanol. [4] The method according to any one of [1] to [3] wherein the acid is hydrochloric acid. [5] as the [1] The method of any one of [3], wherein the acid is sulfuric acid. The method of any one of [1] to [5], wherein the amount of water present in the step (1) is sufficient The method of any one of [1] to [6], wherein in the step (1), 2-amino-3-chloro-5 is present in relation to 1 mol. -Trifluoromethylpyridine is a mixture of at least 2 moles (preferably 6 to 10 moles) of 35 to 50% aqueous sodium hydroxide solution or a relative amount of aqueous sodium hydroxide solution, sodium hydroxide solids and water. The method of any one of [1] to [7], wherein in the step (1), the total amount of water and the solvent is at least 7% (preferably 14.8 to 79% and [20] The method of any one of [1] to [8], wherein in the step (1), 2-amino-3 is used relative to 1 mol. -Chloro-5-trifluoromethylpyridine is 0.8 to 1.2 moles (preferably 1 to 1 〇 5 moles) of 2,4-dichloro-3,5-dinitrobenzyltrifluoride [10 The method according to any one of the above [9], wherein the amount of the solvent 200909419 is 50 to 1000 g with respect to 100 g of 2-amino-3-chloro-5-trifluoromethylpyridine (preferably). The method of any one of [1] to [5], wherein in the step (2), the 3-chloro-N- (3) is contained as a reaction product. -chloro-5-three A mixture of methyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine is separated from the solvent and the organic phase is neutralized or acidified by acid. [12] The method according to any one of [1], wherein the pH is adjusted to 2 to 7 (preferably 5 to 6) by acid in the step (2). [13] The method according to any one of [1] to [5], [11], or [12], wherein in the step (2), the 3-chloro-N-(3-) is contained as a reaction product A mixture of chloro-5-trifluoromethyl-pyridyl-p-trifluoro-p-nitro-p-toluidine and a solvent is mixed with water and then neutralized or acidified with an acid to precipitate crystals of the product. [14] The method according to any one of [1] to [5], wherein in the step (2), in the presence of α-crystals as the reaction product of the seed crystal, The crystal precipitates. [15] A purified product as a product of 3-chloro-indole-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6_ A method of dinitro-p-toluidine, which comprises rinsing the precipitated crystals with aqueous isopropanol to obtain a product having a relatively pure form of less contaminants. [16] The method of [15], wherein The precipitated crystals are washed with water before being washed with aqueous isopropanol. [17] A method of drying a product comprising drying 3-chloro-indole-(3-chloro-5) as a product under reduced pressure. Trifluoromethyl-2-pyridyl)-α,α,α-trifluoro- 200909419 2,6-dinitro-p-toluene [18] The method of drying the product according to [17], wherein the drying is carried out under a reduced pressure of at most 300 mmHg. [19] The method of drying the product according to [17], wherein the method is at most 200 mmHg The method of drying the product according to any one of [17] to [19], wherein the method is carried out at a temperature of 1 15 ° C or lower than 1 15 ° C. [2] The method of drying the product according to any one of [17] to [19] wherein the drying is carried out at 70 ° C or lower than the temperature of TC. [2 2] a method of 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridinyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine or a salt thereof, It comprises 2-amino-3-chloro-5-trifluoromethylpyridine and 2,4-dichloro-3 in the presence of a base component selected from sodium hydroxide or potassium hydroxide and a tertiary alcohol as a solvent. 5-Dinitrobenzyltrifluoride reaction. According to the invention, 2-amino-3-chloro-5-trifluoromethylpyridine and 2,4-dichloro-3,5-dinitro Benzyl trifluoride reaction to produce 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p- In the method of aniline, not only The desired product can be isolated and purified efficiently and industrially advantageously by a simple process and by using an industrially advantageous reaction system to obtain the desired product with excellent yield. The process of the present invention provides high yields. The desired product is therefore more industrially usable than the conventional method. Furthermore, the method of the present invention is an excellent industrial method from the viewpoints of cost, operability, and safety. Other objects, features, advantages and aspects of the present invention will become apparent from the following description. However, it should be understood that the following description and specific examples of the specification are intended to illustrate the preferred embodiments of the invention. From the following description and the teachings of the remainder of the specification, those skilled in the art can readily appreciate that there are various possible variations and/or modifications within the scope of the invention and the scope of the invention disclosed herein. Modified). All patent documents and reference documents cited in this specification are for illustrative purposes, and it should be understood that their contents are included in this specification as part of this specification. BEST MODE FOR CARRYING OUT THE INVENTION Step (1) above must be carried out at a sufficient alkali concentration (preferably the highest possible alkali concentration or high alkali condition). Alkali components which may be mentioned as basic materials are hydroxides and carbonates of alkali metals and carbonates and alkaline earth metals, and in particular sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate , sodium bicarbonate, potassium hydrogencarbonate, calcium hydroxide, magnesium hydroxide, calcium carbonate and magnesium carbonate. Preferably, sodium hydroxide, potassium hydroxide, calcium hydroxide and magnesium hydroxide can be mentioned. An alkali selected from sodium hydroxide or potassium hydroxide is suitably used in the industry. Sodium hydroxide is particularly suitable because it can be purchased commercially at a low price. Although other alkaline substances may be used in place of sodium hydroxide, for the sake of simplicity, the present invention will describe the use of sodium hydroxide as a typical example of the basic substance. In the step (1), although not particularly limited, the amount of the alkali component may be at least 5 g / 1 〇 〇 g tertiary alcohol. For example, at least 5 g (preferably at least 8 g and particularly preferably at least -10 200909419 10 g) of sodium hydroxide may be present in the reaction system relative to 100 g of tert-butanol. Typically, the reaction system contains 10 to 50 g (preferably 12 to 30 g and particularly preferably 13 to 20 g) of a base such as sodium hydroxide with respect to 100 g of tert-butanol as a solvent. In this step (1), it is feasible and suitable to add an amount of water sufficient to substantially dissolve the base. In this step (in the oxime, at least 2 moles (preferably 6 to 10 moles) may be present in the reaction system relative to 1 mole of 2-amino-3. chloro-5-trifluoromethylpyridine. a base component (for example, at least 2 moles (preferably 6 to 10 moles) of a 30 to 50% aqueous sodium hydroxide solution or a corresponding amount of a base such as sodium hydroxide and water. The aqueous alkali solution in the reaction solution The concentration of (such as the above aqueous sodium hydroxide solution) is preferably 35 to 50% (particularly 37 to 48%). Of course, by using an aqueous alkali solution (such as sodium hydroxide) which is prepared in advance and has a predetermined concentration An aqueous solution or a corresponding amount of a base such as sodium hydroxide and water may be added to the reaction system. When a material containing water (such as a solvent for recycling) is used for the reaction, it is considered in the material. For the water, a solid base such as sodium hydroxide and water may be used so that the above aqueous solution is present in the reactor, and the present invention encompasses the case. For example, as long as the base in the reaction system (such as sodium hydroxide) is When the desired product is separated, it is not a crystalline or solid type, which can improve the inverse a concentration of an aqueous alkali solution (such as an aqueous sodium hydroxide solution) in the system. In the step (1), although the reaction can be carried out in the absence of water in the reaction system, the reaction is preferably substantially contained. The reaction system of water is carried out. The reaction system substantially contains water, meaning that the amount of water is sufficient to prevent the base (such as sodium hydroxide) from being crystalline or solid, so that when the desired product is separated after the reaction, it is not necessary to use the solid phase. /liquid phase separation (such as filtration from -11 - 200909419) to separate the base or to dissolve the base by adding water. For example, the amount of water may be at least 7% (preferably 1 4.8) relative to the total amount of water and solvent. Up to 7 9 ° /.), and typically 20 to 4 % water. In this step (1), relative to 1 mole of 2-amino-3-chloro-5-trifluoromethyl For pyridine, 0.8 to 1.2 moles of 2,4-dichloro-3,5-dinitrobenzyltrifluoride can be used. Preferably, relative to 1 mole of 2-amino-3-chloro-5- As the trifluoromethylpyridine, 1 to 1.05 mol of 2,4-dichloro-3,5-dinitrobenzyltrifluoride can be used. The reaction (1) is 2-amino-3-chloro- 5-trifluoromethylpyridine Condensation of 2,4-dichloro-3,5-dinitrobenzyltrifluoride, and although theoretically equivalent molar amount of 2-amino-3-chloro-5-trifluoromethylpyridine and 2 , 4-dichloro-3,5-dinitrobenzyltrifluoride, but due to the slight loss of 2,4-dichloro-3,5-dinitrobenzyltrifluoride, preferably the two The ratio of use of the starting materials falls within the above range. However, the ratio may be outside the above range. In the step (1), relative to 100 g of 2-amino-3-chloro-5-trifluoromethyl As the pyridine, 50 to 1000 g (preferably 100 to 700 g) of a solvent can be used. The solvent used in the method of the present invention is selected from tertiary alcohols such as tert-butyl alcohol and pivalanol. The use of this solvent is not only suitable for achieving a higher yield of the reaction (1), but also greatly simplifies the operation of the process of the present invention to achieve the desired product. The solvent may be miscible with water or form a low boiling azeotrope with water. Considering that the reaction is exothermic and 2,4-dichloro-3,5-dinitrobenzyltrifluoro is susceptible to hydrolysis to determine the reaction procedure of step (1) (such as starting materials and solvent fed to the reactor) order). The preferred procedure involves first feeding 2-amino-3-chloro-5-trifluoromethylpyridine and a predetermined amount of solvent to the reactor, mixing, and then feeding the aqueous base (such as aqueous sodium hydroxide). And/or base-12-200909419 (such as sodium hydroxide solid), if necessary, further adding solvent and / or water to adjust the alkalinity of the resulting solution, mixing the resulting solution, cooling the resulting mixture to 5 to At 30 ° C, 2,4-dichloro-3,5-dinitrobenzyltrifluoride dissolved in the solvent was fed. The procedure can be appropriately modified by considering the price of the starting reactant to be used and the reaction conditions. The reaction temperature is between 4 ° C (preferably 15 to 35 ° C). The reaction time is about 5 to 5 hours (preferably about 1 · 〇 to 3 · 5 hours). The reaction can be carried out under 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 acid neutralized or acidified to deactivate the excess base in the reaction mixture and the free reaction product is released from the salt by a base such as sodium. In this step (2) In the reaction mixture obtained after completion of the reaction (1) by acid neutralization or acidification. Although any acid of any concentration can be used (as long as the acid can be neutralized or acidified from the reaction (the reaction mixture obtained after completion), but the industrial availability is considered, the acid is preferably hydrochloric acid or sulfuric acid. The amount of the acid is such that the amount of the reaction mixture can be neutralized or acidified. When a high concentration of acid is used, water can be added to the reactor in advance. For example, in the step (2), the step can be taken (1) The pH of the reaction mixture obtained after the adjustment is adjusted to 2 to 7 (preferably 5 to 6). Further, in the step (2), the reaction mixture obtained from the step (1) may be directly neutralized or The acidified or organic phase separated from the reaction mixture may be neutralized or acidified. In the process of the present invention, since the reaction product is formed in the form of an alkali salt (such as a sodium salt) and is transferred to the organic phase, -13- 200909419 There is no product loss when separating the reaction mixture. Adding water to the reactor before the separation will remove excess sodium hydroxide or a salt formed from the reaction (such as sodium chloride) and advantageously in the subsequent And or acidify the organic phase when the pressure is low Should be the volume of the system. In this step (2), it contains 3-chloro-N-(3-chloro-5-trifluoromethyl-2.pyridyl)-α,α,α-trifluoro-2,6 a 3-chloro-N-(3-chloro-5-difluoromethyl-2-pyridyl)-indole 1 as a reaction product when a mixture of dinitro-3⁄4 toluidine and a solvent is neutralized or acidified 〇1, 〇1-trifluoro-2,6-dinitro-p-toluidine is crystallized in water. The solvent used in the step (2) is the same as the user of the step (1). The solvent is removed by distillation from 1 to 65 ° C and optionally under reduced pressure. The solvent to be removed is typically recovered in the form of a water azeotrope and can be recycled in the process of the invention. Crystallization of the desired product obtained by the invention (such as 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro - p-toluidine (formerly known as fluorescein) crystals are disclosed in the insecticide manual (the third edition) and similar literature and are pale yellow crystals with a melting point of Π5-1 17 ° C (called It is α crystal.) Different crystal forms with lower melting point are called ruthenium crystals. The manufacturing process control requires a stable manufacturing method of α crystal. In this step (2), the crystallization can be carried out in the presence of α crystal as a product of the seed crystal. In the step (2), the crystal precipitated in water can be It is easily recovered by a conventional filtration method. 3-Chloro-indole-(3-chloro-5-trifluoromethyl-2-pyridin-14-200909419-base)-α,α precipitated in the step (2) The crystallization of α-trifluoro-2,6-dinitro-p-toluidine can be purified by rinsing with aqueous isopropanol. In the purification process via rinsing, the starting material is washed with aqueous isopropanol. It may be previously rinsed with water. The amount of water in the aqueous isopropanol for rinsing may be appropriately selected so as not to substantially dissolve the desired 3-chloro-indole-(3-chloro-5-trifluoromethyl) Crystallization of yl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine. Low water content of isopropanol (IPΑ) adversely dissolves the desired 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2 , Crystallization of 6-dinitro-p-toluidine. Typically, up to 90% aqueous isopropanol solution (preferably up to 85% aqueous solution of isopropanol) is used. The aqueous isopropyl alcohol is used in an amount of from 50 to 500 g (preferably from 100 to 200 g) relative to the crystal of the desired product of the starting material of 1 〇〇 g. The 3-chloro(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6- precipitated in the step (2) is washed with aqueous isopropanol. The results of crystallization of dinitro-p-toluidine are illustrated below. When the initial crystals were washed with an 85% aqueous solution of isopropanol (PhOH derivative, 0.25; impurity 1 '0.63; impurity 2, 0.80; other impurities, 2.27; desired product, 96.05), crystals were obtained after washing (PhOH derived). Matter, 0; impurity 1,0; impurity 2,0; other impurities, 0.74; desired product, 99.26). The PhOH derivative represents a decomposition product of 2,4-dichloro-3,5-dinitrobenzyltrifluoride (DCDNBTF). Impurity 1 represents 2-amino-3-chloro-5-trifluoromethylpyridine ( ACTF), impurity 2 represents DCDNBTF, and the desired product represents 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6 - Dinitro-p-toluidine. The obtained product 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine is suitably Drying -15-200909419 under reduced pressure to produce a highly purified dried product. In the method of drying the product, the optimum conditions can be appropriately selected from the conditions for decomposing the desired product, and for example, the drying can be carried out under a reduced pressure of at most 300 mm Hg or a reduced pressure of at most 200 mmHg. In the drying method, the product may be dried at a temperature of, for example, Π 5 ° C or lower than 1 15 ° C or dried at a temperature of 70 ° C or lower. The drying method is effective for providing an agent for the active ingredient of the insecticide having a good purity. The resulting crystals are formulated with different adjuvants to form a powder, wettable powder or suspension product. Now, the present invention will be described in detail with reference to the embodiments. However, the examples are for illustrative purposes only and are not intended to limit or limit the scope of the invention. It should be understood that the present invention can be implemented in different modes based on the concept in this specification. All embodiments may be implemented or practiced by standard techniques known or conventional to those skilled in the art. EXAMPLES Example 1 2-Amino-3-chloro-5-trifluoromethylpyridine (A c TF; purity 9 9 %, 24.8 g '0.125 mol) and tert-butanol (96 g) were fed. It was placed in a four-necked flask equipped with a stirrer, a temperature vessel and a dropping funnel and then mixed with 99% NaOH (15'2 g, 0_3 75 mol) with stirring. Cooling the resulting mixture to about 10 ° C and adding 2,4-dichloro-3,5-nitroguanidine difluoride (DCDNBTF) powder at a temperature maintained at 3 CTC or below (TC) 98.3%, 40.48 g -16 - 200909419, 0.1 3 1 mole. Then the reaction was allowed to proceed at room temperature for about 3 hours. After adding water (50 g), the reaction mixture was passed through 70% sulfuric acid (15 g). Neutralizing to pH 5 to 6 to precipitate crystals. The reaction solution is cooled until the internal temperature reaches about 20 t or less and the resulting slurry is filtered under reduced pressure. The resulting filter cake is passed through water ( 100 g) and 85% aqueous solution of isopropanol (80 g) were rinsed. The resulting yellow crystals were dried at 60 ° C to give 3-chloro-N-(3-chloro-5-trifluoromethyl-2 -aziridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine (45.5 8 g, mp. 1 17-1 1 9.5 Τ). Example 2 ACTF (purity 99) %, 24.8 g, 0.125 mol) and tert-butyl alcohol (106.6 g) containing 10% water were fed to a four-necked flask equipped with a stirrer, thermometer and dropping funnel and then stirred with 48% aqueous NaOH solution. (80.6 g) was mixed with NaOH flakes (2.6 g, purity 99%). The resulting mixture was added to about 10 ° C and DCDNBTF powder (purity 99.2%, 39.60 g, 0.129 mol) was added at a temperature maintained at 30 ° C or lower. The reaction was then allowed to pass to the chamber. The temperature was carried out for about 1 hour. Water (25 g) was added to the reaction mixture and the aqueous phase separated into the lower layer was removed. Water (54 g) was added to the t-butanol layer and then added dropwise for Neutralize 70% sulfuric acid until the pH reaches 5 to 6 to precipitate crystals. After adding water (50 g), the tert-butanol is removed by distillation under reduced pressure (150 mmHg) until the internal temperature reaches 60 °C. The residue was slowly cooled to an internal temperature of about 2 ° C and the resulting slurry was filtered under reduced pressure. The resulting cake was rinsed with water (100 g) and 85% aqueous isopropyl alcohol (80 g). The resulting yellow -17-200909419 crystallized at 6 (dry under TC to give 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-1 〇, 〇 1-three Fluorin-2,6-dinitro-p-toluidine (45. 〇〇§). Example 3 ACTF (purity 99%, 24.8 g, 0.125 mol) and tert-butanol (106.6 g) containing 10% water Feeded to equipped with a stirrer, temperature The four-necked flask was taken up in the dropping funnel and then mixed with a 48% Na〇H aqueous solution (80.6 g) and a NaOH flake (2.6 g, purity 99%) with stirring. The resulting mixture was cooled to about 20 ° C and DCDNBTF powder (purity 98.3%, 40.0 g, 0. 129 moles) was added at a temperature maintained at 30 ° C or below. The reaction is then allowed to proceed at a temperature between 20 and 30 ° C for about 1 hour. Water (73.7 g) was added to the reaction mixture and the separated aqueous layer was removed. The t-butanol layer is heated in warm water and slowly added dropwise (about 1.0 ml/min) to the neutralized 5% sulfuric acid until the pH reaches 5 to 6 to precipitate crystals (while maintaining the temperature between S) 5 ° C to 60 ° C). When the crystallization began to precipitate (at a pH of about 8), α crystal (〇.〇5 g) as a seed crystal was added. After the dropwise addition, the crystals were aged at 55 ° C to 60 ° C and stirred for 30 minutes. The reaction solution was cooled to an internal temperature of about 20 ° C or below and the resulting slurry was filtered under reduced pressure. The resulting filter cake was rinsed with water (101.7 g) and 85 % aqueous isopropanol (66.6 g). The resulting yellow crystals were dried at 60 ° C to give 3-chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-(*, 〇1, (1-trifluoro) -2,6-dinitro-p-toluidine (42.0 §). Example 4 • 18 - 200909419 ACTF (purity 99%, 19_9 g '0_10 mol) and tert-butanol (85.2 g) containing 10% water It was fed into a four-necked flask equipped with a stirrer, a thermometer and a dropping funnel and then mixed with a 48% aqueous NaOH solution (64.5 g) and a Na Ο Η sheet (2.1 g, purity 99%) with stirring. Cool the resulting mixture to about 20 ° C and add 〇 〇 〇 ? powder (purity 98.3%, 32.0 §, 0.103 mol) at a temperature of 30 ° C or below (TC). The reaction is carried out at a temperature of from 20 to 3 (TC for about 1 hour. Water (5 9 · 0 g) is added to the reaction mixture and the separated aqueous layer is removed. Heating 10% sulfuric acid to 60 ° C And mixed with α crystal (〇.〇4 g) as a seed crystal. The mixture for neutralization is slowly added dropwise (about 1.0 ml/min) to the tertiary alcohol layer until P Η 5 to 6 Precipitate crystallization (while maintaining the temperature between 55 ° C 6(TC). After the dropwise addition, the crystal is aged at 55t to 60 ° C and stirred for 30 minutes. The reaction solution is cooled to an internal temperature of about 2 CTC or less and at 20 ° C under reduced pressure. The resulting slurry was filtered, and the resulting filter cake was washed with water (8 1.4 g) and 85% aqueous solution of isopropyl alcohol (53.3 g). The resulting yellow crystals were dried at 6 ° C to form 3-Chloro-N-(3-chloro-5-trifluoromethyl-2-pyridyl)-α,α,α-trifluoro-2,6-dinitro-p-toluidine (34.4 g). The present invention can efficiently obtain a purity preparation of an insecticide active ingredient (Fluoric Acid) in a good yield and in an industrially advantageous manner, and can be separated and purified from a reaction system for synthesizing fluorine. The product can efficiently obtain a dry preparation of the desired product in a low cost and simple operation. Therefore, the method of the present invention is an industrially excellent method. Obviously, the present specification or the foregoing embodiment can be used. The present invention is embodied in other modes than those described, and many modifications and/or changes to the present invention are possible based on the teachings of the present invention. It is possible and is within the scope of the appended patent application. Japanese Patent Application No. 2007-202362 (filed on August 2, 2007) and Japanese Patent Application No. 2008-037635 (in 2008) The entire contents (including the specification, the scope of the patent application and the abstract) disclosed in the application on the 19th of the present application are incorporated herein by reference. -20-