TW201010989A - Amide compound and use thereof - Google Patents
Amide compound and use thereof Download PDFInfo
- Publication number
- TW201010989A TW201010989A TW98119052A TW98119052A TW201010989A TW 201010989 A TW201010989 A TW 201010989A TW 98119052 A TW98119052 A TW 98119052A TW 98119052 A TW98119052 A TW 98119052A TW 201010989 A TW201010989 A TW 201010989A
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- benzothiazole
- phenyl
- carboxamide
- compound
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
201010989 六、發明說明 【發明所屬之技術領域】 本發明係關於醯胺化合物及其防治植物疾病之用途。 【先前技術】 一些化合物已發展作爲植物疾病防治組成物的活性成 分且進行應用。然而,這些化合物於一些情況中不一定顯 〇 示充分的植物疾病防治效果。 【發明內容】 本發明提供對植物疾病具有優異防治效果之化合物。 本發明如下。 [1]一種式(I)之醯胺化合物:201010989 VI. Description of the Invention [Technical Field to Which the Invention Is Applicable] The present invention relates to a guanamine compound and its use for controlling plant diseases. [Prior Art] Some compounds have been developed and used as active ingredients of plant disease control compositions. However, these compounds do not necessarily indicate sufficient plant disease control effects in some cases. SUMMARY OF THE INVENTION The present invention provides a compound having an excellent control effect on plant diseases. The invention is as follows. [1] A guanamine compound of the formula (I):
其中’ R1表示氫原子或氟原子,和R2表示C3-C8直 鏈烯基或C3-C8直鏈炔基。 (下文稱爲本發明化合物)。 [2] 如[1]之醯胺化合物,其中Ri爲氟原子,和R2爲 C3-C8直鏈烯基。 [3] 如[2]之醯胺化合物,其中R2爲C5-C7直鏈烯基。 [4] 如[2]之醯胺化合物,其中R2爲4_戊烯基、5_己烯 基或6-庚烯基。 201010989 [5] 如[1]之醯胺化合物,其中R1爲氫原子,和R2爲 C3-C8直鏈烯基。 [6] 如[5]之醯胺化合物,其中R2爲C5-C7直鏈烯基。 [7] 如[5]之醯胺化合物,其中R2爲4-戊烯基、5-己嫌 基或6-庚烯基。 [8] 如[1]之醯胺化合物,其中R1爲氟原子,和爲 C 3 _ C 8直鏈炔基。 [9] 如[8]之醯胺化合物,其中R2爲C5-C7直鏈炔基。 [10] 如[8]之醯胺化合物,其中R2爲4-戊炔基、5-己 炔基或6-庚炔基。 [11] 如[1]之醯胺化合物,其中R1爲氫原子,和R2爲 C 3 - C 8直鏈炔基。 [12] 如[11]之醯胺化合物,其中R2爲C5-C7直鏈块 基。 [13] 如[11]之醯胺化合物,其中R2爲4_戊炔基、5_己 炔基或6-庚炔基。 [14] 一種植物疾病防治組成物,其包括如[1]至tl 3]中 之任一者所述之醯胺化合物和惰性載劑。 (下文稱爲本發明之植物疾病防治組成物) [15] —種植物疾病防治方法,其具有將有效量之如 至[13]中之任一者所述之醯胺化合物施加至植物或土壤之 步驟。 (下文稱爲本發明之植物疾病防治方法) [16] —種如[1]至[13]中之任一者所述之醯胺化合物於 -6 - 201010989 防治植物疾病之用途。 [17] N-(2-氟- 3-(2 -丙烯氧基)苯基)甲基-苯並噻唑- 6- 羧醯胺。 [18] N-(2-氟-3-(4_戊烯氧基)苯基)甲基-苯並噠唑-6- 羧醯胺。 [19] N-(2-氟- 3-(5-己烯氧基)苯基)甲基-苯並噻唑- 6- 羧醯胺。 φ [20] N-(2-氟-3-(6-庚烯氧基)苯基)甲基-苯並噻唑-6- 羧醯胺。 [21] N-(2-氟- 3-(2-戊烯氧基)苯基)甲基-苯並噻唑- 6- 羧醯胺。 [22] N-(3-(2-丙烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [23] N-(3-(4-戊烯氧基)苯基)甲基-苯並噻唑-6_羧醯 胺。 Φ [24] N-(3-(5-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [25] N-(3_(6-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [26] N-(3-(2-丁烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [27] N-(3-(2-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [28] N-(2-氟-3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6- 201010989 羧醯胺。 [29] N-(2-氟- 3-(4-戊炔氧基)苯基)甲基-苯並噻唑- 6-羧醯胺。 [3 0] N-(2-氟- 3-(5-己炔氧基)苯基)甲基-苯並噻唑- 6-羧醯胺。 [31] N-(2-氟- 3-(2-戊炔氧基)苯基)甲基-苯並噻唑- 6-羧醯胺。 [32] N-(3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6-羧醯 參 胺。 [33] N-(3-(4-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 [34] N-(3-(5-己炔氧基)苯基)甲基-苯並唾唑-6-羧醯 胺。 [35] N-(3-(2-丁炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。Wherein 'R1 represents a hydrogen atom or a fluorine atom, and R2 represents a C3-C8 linear alkenyl group or a C3-C8 linear alkynyl group. (hereinafter referred to as the compound of the present invention). [2] A guanamine compound according to [1], wherein Ri is a fluorine atom, and R2 is a C3-C8 linear alkenyl group. [3] A guanamine compound according to [2], wherein R2 is a C5-C7 linear alkenyl group. [4] A guanamine compound according to [2], wherein R2 is 4-pentenyl, 5-hexenyl or 6-heptenyl. [10] The indoleamine compound of [1], wherein R1 is a hydrogen atom, and R2 is a C3-C8 linear alkenyl group. [6] A guanamine compound according to [5], wherein R2 is a C5-C7 linear alkenyl group. [7] A guanamine compound according to [5], wherein R2 is 4-pentenyl, 5-hexyl or 6-heptenyl. [8] The guanamine compound according to [1], wherein R1 is a fluorine atom, and is a C 3 - C 8 linear alkynyl group. [9] A guanamine compound according to [8], wherein R2 is a C5-C7 linear alkynyl group. [10] A guanamine compound according to [8], wherein R2 is 4-pentynyl, 5-hexynyl or 6-heptynyl. [11] A guanamine compound according to [1], wherein R1 is a hydrogen atom, and R2 is a C3-C8 linear alkynyl group. [12] A guanamine compound according to [11], wherein R2 is a C5-C7 linear block group. [13] A guanamine compound according to [11], wherein R2 is 4-pentynyl, 5-hexynyl or 6-heptynyl. [14] A plant disease controlling composition comprising the indoleamine compound and an inert carrier as described in any one of [1] to t13]. (hereinafter referred to as the plant disease control composition of the present invention) [15] - A method for controlling plant diseases, which has an effective amount of the indoleamine compound as described in any one of [13] applied to a plant or soil The steps. (The method for controlling plant diseases according to the present invention) [16] The use of the indoleamine compound according to any one of [1] to [13] for controlling plant diseases in -6 - 201010989. [17] N-(2-Fluoro-3-(2-propenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [18] N-(2-Fluoro-3-(4-pentenyloxy)phenyl)methyl-benzoxazol-6-carboxyguanamine. [19] N-(2-Fluoro-3-(5-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. φ [20] N-(2-Fluoro-3-(6-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [21] N-(2-Fluoro-3-(2-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [22] N-(3-(2-Propoxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [23] N-(3-(4-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxyindole Amine. Φ [24] N-(3-(5-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [25] N-(3_(6-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine. [26] N-(3-(2-Butoxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine. [27] N-(3-(2-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine. [28] N-(2-Fluoro-3-(2-propynyloxy)phenyl)methyl-benzothiazole-6- 201010989 Carboxamide. [29] N-(2-Fluoro-3-(4-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [3 0] N-(2-Fluoro-3-(5-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [31] N-(2-Fluoro-3-(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [32] N-(3-(2-propynyloxy)phenyl)methyl-benzothiazole-6-carboxyindole amide. [33] N-(3-(4-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine. [34] N-(3-(5-hexynyloxy)phenyl)methyl-benzosoxaconazole-6-carboxyindoleamine. [35] N-(3-(2-butynyloxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine.
[36] N-(3-(2-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯 G 胺。 [37] N-(2-氟-3_ (2-丁炔氧基)苯基)甲基-苯並噻唑- 6-羧醯胺。 [38] N-(2-氟- 3-(7-辛烯氧基)苯基)甲基-苯並噻唑- 6-羧醯胺。 [39] N-(3-(7-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺。 本發明化合物包括例如下面具體例。 -8- 201010989 式(I)中之R2表示2-丙烯基之醯胺化合物; 式(I)中之R2表示2_丙炔基之醯胺化合物; 式(I)中之R2表示C4-C6直鏈烯基之醯胺化合物; 式(I)中之R2表示C4-C6直鏈炔基之醯胺化合物; R1表示氫原子且R2表示CM-C6直鏈烯基之醯胺化合 物; R1表示氫原子且R2表示C4-C6直鏈炔基之醯胺化合 φ 物; R1表示氟原子且R2表示C4-C6直鏈烯基之醯胺化合 物;和 R1表示氟原子且R2表示C4-C6直鏈炔基之醯胺化合 物。 R2所示之C3-C 8直鏈烯基包括丙烯基、直鏈丁烯 基、直鏈戊烯基、直鏈己烯基、直鏈庚烯基和直鏈辛烯 基。丙烯基的範例包括2-丙烯基。直鏈丁烯基的範例包 Ο 括2-丁烯基、和3-丁烯基。直鏈戊烯基的範例包括2-戊 烯基、3-戊烯基和4-戊烯基。直鏈己烯基的範例包括2-己烯基、3-己烯基、4-己烯基和5-己烯基。直鏈庚烯基的 範例包括2-庚烯基、3-庚烯基、4-庚烯基、5-庚烯基和6-庚烯基。直鏈辛烯基的範例包括2-辛烯基、3-辛烯基、4-辛烯基、5-辛烯基、6-辛烯基和7-辛烯基。 R2所示之C3-C 8直鏈炔基包括丙炔基、直鏈丁炔 基、直鏈戊炔基、直鏈己炔基、直鏈庚炔基和直鏈辛炔 基。丙炔基的範例包括2-丙炔基。直鏈丁炔基的範例包 -9 - 201010989 括2-丁炔基和3-丁炔基。直鏈戊炔基的範例包括2-戊炔 基、3-戊炔基和4-戊炔基。直鏈己炔基的範例包括2-己 块基、3-己块基、4-己炔基和5-己炔基。直鏈庚炔基的範 例包括2-庚炔基、3-庚炔基、4-庚炔基、5-庚炔基和6-庚 炔基。直鏈辛炔基的範例包括2-辛炔基、3-辛炔基、4-辛 炔基、5-辛炔基、6-辛炔基和7-辛炔基。 將描述本發明化合物之製造方法。 本發明化合物可以例如藉由下面(製造方法1)至(製造 Q 方法3)予以製備。 (製造方法1) 本發明化合物可以藉由使化合物(Π)、化合物(III)或 其鹽(例如,可提及者爲氫氯酸和氫溴酸)和縮合劑反應而 予以製造。[36] N-(3-(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxyindole G amine. [37] N-(2-Fluoro-3_(2-butynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [38] N-(2-Fluoro-3-(7-octenyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine. [39] N-(3-(7-Octyloxy)phenyl)methyl-benzothiazole-6-carboxyindoleamine. The compounds of the present invention include, for example, the following specific examples. -8- 201010989 R2 in the formula (I) represents a 2-propenylamine compound; R2 in the formula (I) represents a 2-propynylamine derivative; and R2 in the formula (I) represents a C4-C6 a linear alkenyl amidoxime compound; R2 in the formula (I) represents a C4-C6 linear alkynyl amidoxime compound; R1 represents a hydrogen atom and R2 represents a CM-C6 linear alkenyl amidoxime compound; R1 represents a hydrogen atom and R2 represents a decylamine compound of a C4-C6 linear alkynyl group; R1 represents a fluorine atom and R2 represents a decylamine compound of a C4-C6 linear alkenyl group; and R1 represents a fluorine atom and R2 represents a C4-C6 straight An alkynyl group of amidoxime compounds. The C3-C8 linear alkenyl group represented by R2 includes a propenyl group, a linear butenyl group, a linear pentenyl group, a linear hexenyl group, a linear heptenyl group, and a linear octene group. Examples of the propylene group include a 2-propenyl group. Examples of linear butenyl groups include 2-butenyl, and 3-butenyl. Examples of linear pentenyl groups include 2-pentenyl, 3-pentenyl and 4-pentenyl. Examples of linear hexenyl groups include 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl. Examples of linear heptenyl groups include 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl and 6-heptenyl. Examples of linear octenyl groups include 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl and 7-octenyl. The C3-C8 linear alkynyl group represented by R2 includes a propynyl group, a linear butynyl group, a linear pentynyl group, a linear hexynyl group, a linear heptynyl group, and a linear octynyl group. Examples of propynyl include 2-propynyl. An example package of a linear butynyl group -9 - 201010989 includes 2-butynyl and 3-butynyl. Examples of linear pentynyl groups include 2-pentynyl, 3-pentynyl and 4-pentynyl. Examples of linear hexynyl groups include 2-hexyl, 3-hexyl, 4-hexynyl and 5-hexynyl. Examples of linear heptynyl groups include 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl and 6-heptynyl. Examples of linear octynyl groups include 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl and 7-octynyl. A method of producing the compound of the present invention will be described. The compound of the present invention can be produced, for example, by the following (manufacturing method 1) to (manufacturing Q method 3). (Production Method 1) The compound of the present invention can be produced by reacting a compound (Π), a compound (III) or a salt thereof (for example, hydrochloric acid and hydrobromic acid may be mentioned) with a condensing agent.
(其中,R1和R2表示與上述相同之意義)。 反應通常是在溶劑存在下進行。 反應中所使用之溶劑的範例包括醚類如四氫呋喃(下 文稱爲THF)、乙二醇二甲基醚、三級丁基甲基醚(下文稱 爲MTBE)等等;脂族烴類如己烷、庚烷、辛烷等等;芳 -10- 201010989 香族烴類如甲苯、二甲苯等等;鹵化的烴類如氯苯等等; 酯類如乙酸丁酯、乙酸乙酯等等;腈類如乙腈等等;醯胺 類如N,N-二甲基甲醯胺(下文稱爲DMF)等等;亞颯類如 二甲基亞碾(下文稱爲DMSO)等等;含氮之芳香族化合物 如吡啶等等;及其混合物。 反應中所使用之縮合劑的範例包括碳二醯亞胺類如 1-乙基- 3-(3-二甲基胺基丙基)碳二醯亞胺鹽酸鹽(下文稱 φ 爲wsc)、1,3-二環己基碳二醯亞胺等等、和六氟磷酸(苯 並三唑-1-基氧基)三(二甲基胺基)鱗(下文稱爲BOP試 劑)。 於反應中,化合物(III)的用量比例通常爲0.5至3 mol,基於1 mol的化合物(II)計,且縮合劑的用量比例通 常爲1至5 mol,基於1 mol化合物(II)計。 反應的反應溫度範圍通常爲-2(TC至140°C。反應的反 應時間範圍通常爲1至24小時。 ® 反應結束之後,若固體藉由將水加到反應混合物中而 沈澱,則本發明化合物可以經由過濾而分離出來。若藉由 將水加到反應混合物中而未發生固體沈澱,則本發明化合 物可以藉由用有機溶劑萃取反應混合物與水的混合物,和 乾燥且濃縮有機層而予以分離。經分離的本發明化合物亦 可以藉由層析術、再結晶等等而進一步予以純化。 (製造方法2) 本發明化合物可以藉由使化合物(IV)或其鹽酸鹽,和 -11 - 201010989 化合物(III)或其鹽(例如,可提及者爲鹽酸鹽和氫溴酸鹽) 在鹼存在下反應而予以製造。(wherein R1 and R2 represent the same meaning as described above). The reaction is usually carried out in the presence of a solvent. Examples of the solvent used in the reaction include ethers such as tetrahydrofuran (hereinafter referred to as THF), ethylene glycol dimethyl ether, tertiary butyl methyl ether (hereinafter referred to as MTBE), and the like; aliphatic hydrocarbons such as hexane, Heptane, octane, etc.; aryl-10- 201010989 aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as chlorobenzene, etc.; esters such as butyl acetate, ethyl acetate, etc.; Such as acetonitrile and the like; guanamines such as N,N-dimethylformamide (hereinafter referred to as DMF) and the like; sulfoxides such as dimethyl sub-milling (hereinafter referred to as DMSO), etc.; nitrogen-containing aroma Group compounds such as pyridine and the like; and mixtures thereof. Examples of the condensing agent used in the reaction include carbodiimides such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (hereinafter referred to as φ is wsc). 1,3-dicyclohexylcarbodiimide or the like, and hexafluorophosphoric acid (benzotriazol-1-yloxy)tris(dimethylamino)scale (hereinafter referred to as BOP reagent). In the reaction, the compound (III) is usually used in an amount of from 0.5 to 3 mol, based on 1 mol of the compound (II), and the proportion of the condensing agent is usually from 1 to 5 mol, based on 1 mol of the compound (II). The reaction temperature of the reaction is usually in the range of -2 (TC to 140 ° C. The reaction time of the reaction is usually in the range of 1 to 24 hours. After the end of the reaction, if the solid is precipitated by adding water to the reaction mixture, the present invention The compound can be isolated by filtration. If solid precipitation does not occur by adding water to the reaction mixture, the compound of the present invention can be obtained by extracting a mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. The isolated compound of the present invention can also be further purified by chromatography, recrystallization, etc. (Production Method 2) The compound of the present invention can be obtained by allowing the compound (IV) or its hydrochloride, and -11 - 201010989 The compound (III) or a salt thereof (for example, a hydrochloride and a hydrobromide salt may be mentioned) is produced by reacting in the presence of a base.
其中,R1和R2表示與上述相同之意義。 反應通常在溶劑存在下進行。 @ 反應中所使用之溶劑的範例包括醚類如THF、乙二醇 二甲基醚、MTBE等等;脂族烴類如己烷、庚烷、辛烷等 等;芳香族烴類如甲苯、二甲苯等等;鹵化的烴類如氯苯 等等;酯類如乙酸丁酯、乙酸乙酯等等;腈類如乙腈等 等;及其混合物。 反應中所使用之鹼的範例包括鹸金屬碳酸鹽類如碳酸 鈉、碳酸鉀等等;三級胺類如三乙胺、二異丙基乙基胺等 等;和含氮之芳香族化合物如吡啶、4-二甲基胺基妣啶等 _ 等。 於反應中,化合物(ΠΙ)的用量比例通常爲0.5至3 mol,基於1 mol的化合物(IV)計,且鹼的用量比例通常 爲1至5 mol,基於1 mol的化合物(IV)計。 反應的反應溫度範圍通常爲-20°C至100°C。反應的反 應時間範圍通常爲〇.1至24小時。 反應結束之後,若固體藉由將水加到反應混合物中而 沈澱,則本發明化合物可以經由過濾而分離出來。若藉由 -12- 201010989 將水加到反應混合物中而未發生固體沈澱,則本發明化合 物可以藉由用有機溶劑萃取反應混合物與水的混合物,和 乾燥且濃縮有機層而予以分離。經分離的本發明化合物亦 可以藉由層析術、再結晶等等而進一步予以純化。 (製造方法3)Wherein R1 and R2 represent the same meanings as described above. The reaction is usually carried out in the presence of a solvent. Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, MTBE, etc.; aliphatic hydrocarbons such as hexane, heptane, octane, etc.; aromatic hydrocarbons such as toluene, Xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butyl acetate, ethyl acetate and the like; nitriles such as acetonitrile and the like; and mixtures thereof. Examples of the base used in the reaction include base metal carbonates such as sodium carbonate, potassium carbonate and the like; tertiary amines such as triethylamine, diisopropylethylamine and the like; and nitrogen-containing aromatic compounds such as Pyridine, 4-dimethylamino acridine, etc., etc. In the reaction, the compound (ΠΙ) is usually used in an amount of from 0.5 to 3 mol, based on 1 mol of the compound (IV), and the amount of the base is usually from 1 to 5 mol, based on 1 mol of the compound (IV). The reaction temperature of the reaction is usually in the range of -20 ° C to 100 ° C. The reaction time for the reaction is usually in the range of from 〇1 to 24 hours. After the end of the reaction, if the solid is precipitated by adding water to the reaction mixture, the compound of the present invention can be isolated by filtration. If water is added to the reaction mixture by -12-201010989 without solid precipitation, the compound of the present invention can be isolated by extracting a mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. The isolated compound of the invention can also be further purified by chromatography, recrystallization, and the like. (Manufacturing method 3)
本發明化合物可以藉由使化合物(V)和化合物(VI)在 鹼的存在下反應而予以製造。The compound of the present invention can be produced by reacting the compound (V) and the compound (VI) in the presence of a base.
其中,R1和R2表示與上述相同之意義,且L表示氯原 子、溴原子、碘原子、甲擴醯氧基、三氛甲擴醯氧基或 對-甲苯磺醯氧基。 ❹ 反應通常係在溶劑存在下進行。 反應中所使用之溶劑的範例包括醚類如THF、乙二醇 二甲基醚、MTBE等等;芳香族烴類如甲苯、二甲苯等 等;鹵化的烴類如氯苯等等;腈類如乙腈等等;醯胺如 DMF等等;亞碾類如DMSO等等;酮類如丙酮、甲基乙 基酮、甲基異丁基酮等等;水;及其混合物。 反應中所使用之鹼的範例包括鹼金屬碳酸鹽類如碳酸 鈉、碳酸鉀、碳酸鉋等等;鹼金屬氫氧化物如氫氧化鈉等 等,和鹼金屬氫化物如氫化鈉等等。 -13- 201010989 於反應中,化合物(VI)的用量比例通常爲1至10 mol’基於1 mol的化合物(V)計,且驗的用量比例通常爲 1至5 mol,基於1 mol的化合物(V)計。 反應的反應溫度範圍通常爲-20°C至100°C。反應的反 應時間範圍通常爲0.1至2 4小時。 反應結束之後,若固體藉由將水加到反應混合物中而 沈澱’則本發明化合物可以經由過濾而分離出來。若藉由 將水加到反應混合物中而未發生固體沈澱,則本發明化合 @ 物可以藉由用有機溶劑萃取反應混合物與水的混合物,和 乾燥且濃縮有機層而予以分離。經分離的本發明化合物亦 可以藉由層析術、再結晶等等而進一步予以純化。 化合物(V)可以例如藉由下面(合成方法1)或(合成方 法2)而予以製造。 (合成方法1) 化合物(V)可以藉由使化合物(11)、化合物(VII)或其 Θ 鹽(例如,可提及者爲鹽酸鹽和氫溴酸鹽)和縮合劑反應, 而予以製造。Here, R1 and R2 represent the same meanings as described above, and L represents a chlorine atom, a bromine atom, an iodine atom, a methyl fluorenyloxy group, a trimethyl methoxy group or a p-toluene sulfonyloxy group. The hydrazine reaction is usually carried out in the presence of a solvent. Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, MTBE, etc.; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as chlorobenzene, etc.; nitriles For example, acetonitrile or the like; guanamine such as DMF, etc.; sub-milling such as DMSO, etc.; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.; water; and mixtures thereof. Examples of the base to be used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate, carbonic acid planing, etc.; alkali metal hydroxides such as sodium hydroxide and the like, and alkali metal hydrides such as sodium hydride and the like. -13- 201010989 In the reaction, the ratio of the compound (VI) is usually from 1 to 10 mol' based on 1 mol of the compound (V), and the ratio is usually from 1 to 5 mol based on 1 mol of the compound ( V) meter. The reaction temperature of the reaction is usually in the range of -20 ° C to 100 ° C. The reaction time for the reaction is usually in the range of 0.1 to 24 hours. After the end of the reaction, if the solid is precipitated by adding water to the reaction mixture, the compound of the present invention can be isolated by filtration. If solid precipitation does not occur by adding water to the reaction mixture, the compound of the present invention can be isolated by extracting a mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. The isolated compound of the invention can also be further purified by chromatography, recrystallization, and the like. The compound (V) can be produced, for example, by the following (Synthesis Method 1) or (Synthesis Method 2). (Synthesis Method 1) The compound (V) can be obtained by reacting the compound (11), the compound (VII) or a phosphonium salt thereof (for example, a hydrochloride and a hydrobromide salt) and a condensing agent. Manufacturing.
其中’ R表示與上述相同之意義。 反應通常係在溶劑存在下進行 -14- 201010989 反應中所使用之溶劑的範例包括醚類如THF、乙二醇 二甲基醚、MTBE等等;脂族烴類如己烷、庚烷、辛烷等 等;芳香族烴類如甲苯、二甲苯等等;鹵化的烴類如氯苯 等等;酯類如乙酸丁酯、乙酸乙酯等等;腈類如乙腈等 等;醯胺如DMF等等;亞碾類如DMSO等等;含氮之芳 香族化合物如吡啶等等;及其混合物。 反應中所使用之縮合劑的範例包括碳二醯亞胺類如 〇 WSC、1,3-二環己基碳二醯亞胺等等,和BOP試劑。 於反應中,化合物(VII)的用量比例通常爲0.5至3 mol,基於1 mol的化合物(II)計,且縮合劑的用量比例通 常爲1至5 mol,基於1 mol的化合物(II)計。 反應的反應溫度範圍通常爲-2〇°C至14(TC。反應的反 應時間範圍通常爲1至24小時。 反應結束之後,若固體藉由將水加到反應混合物中而 沈澱,則化合物(V)可以經由過濾而分離出來。若藉由將 水加到反應混合物中而未發生固體沈澱,則化合物(V)可 以藉由用有機溶劑萃取反應混合物與水的混合物,和乾燥 且濃縮有機層而予以分離。經分離的化合物(V)亦可以藉 由層析術、再結晶等等而進一步予以純化。 (合成方法2) 化合物(V)可以藉由使化合物(IV)和化合物(VII)或其 鹽酸鹽於鹼存在下反應而予以製造。 -15- 201010989Wherein 'R denotes the same meaning as described above. The reaction is usually carried out in the presence of a solvent. Examples of the solvent used in the reaction of the-14-201010989 include ethers such as THF, ethylene glycol dimethyl ether, MTBE, etc.; aliphatic hydrocarbons such as hexane, heptane, and octane Alkane or the like; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as chlorobenzene, etc.; esters such as butyl acetate, ethyl acetate, etc.; nitriles such as acetonitrile, etc.; guanamine such as DMF Etc.; sub-milling such as DMSO, etc.; nitrogen-containing aromatic compounds such as pyridine, etc.; and mixtures thereof. Examples of the condensing agent used in the reaction include carbodiimides such as hydrazine WSC, 1,3-dicyclohexylcarbodiimide, and the like, and a BOP reagent. In the reaction, the ratio of the compound (VII) is usually 0.5 to 3 mol, based on 1 mol of the compound (II), and the proportion of the condensing agent is usually 1 to 5 mol, based on 1 mol of the compound (II). . The reaction temperature of the reaction is usually in the range of -2 ° C to 14 (TC. The reaction time of the reaction is usually in the range of 1 to 24 hours. After the end of the reaction, if the solid is precipitated by adding water to the reaction mixture, the compound ( V) can be separated by filtration. If solid precipitation does not occur by adding water to the reaction mixture, the compound (V) can be obtained by extracting a mixture of the reaction mixture and water with an organic solvent, and drying and concentrating the organic layer. Further, the isolated compound (V) can be further purified by chromatography, recrystallization, etc. (Synthesis Method 2) Compound (V) can be obtained by allowing compound (IV) and compound (VII) Or its hydrochloride is produced by reacting in the presence of a base. -15- 201010989
其中,R1表示與上述相同之意義。 反應通常係在溶劑存在下進行。 反應中所使用之溶劑的範例包括醚類如THF、乙二醇 二甲基醚、MTBE等等;脂族烴類如己烷、庚烷、辛焼等 ® 等;芳香族烴類如甲苯、二甲苯等等;鹵化的烴類如氯苯 等等;酯類如乙酸丁酯、乙酸乙酯等等;腈類如乙腈等 等;及其混合物。 反應中所使用之鹸的範例包括鹸金屬碳酸鹽類如碳酸 鈉、碳酸鉀等等;三級胺類如三乙胺、二異丙基乙基胺等 等;和含氮之芳香族化合物如吡啶、二甲基胺基吡啶等 等。 於反應中,化合物(VII)的用量比例通常爲0.5至1 ® mol,基於1 mol的化合物(IV)計,且鹸的用量比例通常 爲1至5 mol,基於1 mol的化合物(IV)計。 反應的反應溫度範圍通常爲-2〇°C至l〇〇°C。反應的反 應時間範圍通常爲〇.1至24小時。 反應結束之後,若固體藉由將水加到反應混合物中而 沈澱,則化合物(V)可以經由過濾而分離出來。若藉由將 水加到反應混合物中而未發生固體沈澱,則化合物(V)可 以藉由用有機溶劑萃取反應混合物與水的混合物,和乾燥 -16- 201010989 且濃縮有機層而予以分離。經分離的化合物(V)亦可以藉 由層析術、再結晶等等而進一步予以純化。 本發明化合物特別包括下面化合物。 N-(2-氟-3-(2-丙烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(2-丁烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, φ N-(2-氟-3-(3-丁烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(2-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(3-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(4-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, Φ N-(2-氟-3-(2-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(3-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(4-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(5-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(2-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯 -17- 201010989 胺, N-(2-氟- 3-(3 -庚烯氧基)苯基)甲基-苯並噻唑-6_羧醯 胺, N-(2-氟- 3-(4-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(5-庚烯氧基)苯基)甲基-苯並噻唑-6_羧醯 胺, N-(2-氟- 3-(6-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯 參 胺, N-(2-氟-3-(2-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醢 胺, N-(2-氟-3-(3-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(4-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(5-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 Θ 胺, N-(2-氟-3-(6-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(7-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(3-(2-丙烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(2-丁烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-丁烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, -18- 201010989 N-(3-(2•戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(4-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(2-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(4-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(5-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, 9 N-(3-(2-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(4-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(5-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(6-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(2-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N_(3_(4-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, φ Ν-(3·(5-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(6-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(7-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(2-氟-3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, Ν_(2-氟-3-(2-丁炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N_(2-.氟-3-(3-丁炔氧基)苯基)甲基·苯並噻唑-6-羧醯 胺, -19 - 201010989 N-(2-氟- 3-(2-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(3-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(4-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(2-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, φ N-(2-氟- 3-(3-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(4-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(5-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(2-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, Θ N-(2-氟-3-(3-庚炔氧基)苯基)甲基-苯並唾唑-6-羧醯 胺, N-(2-氟- 3-(4-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟_3-(5-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(6-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, -20- 201010989 N-(2-氟_3-(2-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(3-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(4-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟- 3-(5-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 ❸胺, N-(2-氟-3-(6-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(2-氟-3-(7-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯 胺, N-(3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺’ N-(3-(2-丁炔氧基)苯基)甲基-苯並噻哇-6-羧醯胺, N-(3-(3-丁炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, # Ν-(3·(2-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(3-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(4-戊炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(2-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(3-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(4-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(5-己炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(2-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, Ν-(3-(3-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, -21 - 201010989 N-(3-(4-rf炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(5-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(6-庚炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(2-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(3-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醢胺, N-(3-(4-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(5-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺, N-(3-(6-辛炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺和 φ N-(3-(7-辛炔氧基)苯基)甲基·苯並噻唑-6-羧醯胺。 本發明之植物疾病防治組成物包含本發明化合物和惰 性載劑。惰性載劑包括固體載劑、液體載劑和氣體載劑。 本發明之植物疾病防治組成物通常藉由進一步加入用於調 合物之助劑如介面活性劑、增黏劑、分散劑、安定劑等等 而被調製成可濕性粉劑、粉劑、水可分散的顆粒、流性 物、顆粒、乾性流性物、乳劑、水性液劑、油性溶液、發 煙劑、氣溶膠、微膠襄等等。本發明之植物疾病防治組成 參 物包含重量比例通常爲0.1至99%(較佳地爲0.2至90%) 之本發明化合物。 固體載劑的範例包括黏土(例如,高嶺土、矽藻土、 合成的水合氧化砂、Fubasami黏土、膨潤土和酸性黏 土)、滑石、其他無機礦物(例如,絹雲母、quart powder、硫粉、活性碳、碳酸鈣和水合矽石)等等的微細 粉末和顆粒,和液體載劑的範例包括水;醇類(例如,甲 醇和乙醇)、酮類(例如,丙酮和甲基乙基酮)、芳香族烴 -22- 201010989 類(例如,苯、甲苯、二甲苯、乙基苯和甲基萘)、脂族烴 類(例如,正己院、環己院和煤油)、醋類(例如,乙酸乙 酯和乙酸丁酯)、腈類(例如,乙腈和異丁腈)、醚類(例 如,二噚卩山和二異丙基醚)、醯胺類(例如,DMF和二甲基 乙醯胺)、鹵化的烴類(例如,二氯乙烷和三氯乙烯、四氯 化碳)等等。 介面活性劑的範例包括硫酸烷酯、磺酸烷酯、磺酸烷 〇 基芳基酯、烷基芳基醚類和其聚氧乙化物 (polyoxyethylenate)、聚氧乙二醇醚(p〇iyOXyethylene glycol ethers)、多價醇酯類、糖醇衍生物等等。 用於調合物之其他助劑的範例包括增黏劑和分散劑, 具體地,酪蛋白、明膠、多醣類(例如,澱粉、阿拉伯 膠、纖維素衍生物和海藻酸)、木質素衍生物、膨潤土、 糖類、合成的水溶性聚合物(例如,聚乙烯醇、聚乙烯吡 咯啶酮和聚丙烯酸)、PAP (酸式磷酸異丙酯)、BHT (2,6-9 二-三級丁基-4-甲基-酚)、BHA (2-三級丁基-4-甲氧基酚 和3-三級丁基-4-甲氧基酚的混合物)、蔬菜油、礦物油、 脂肪酸或其酯類等等。 本發明之植物疾病防治組成物用於防治植物疾病之應 用方法包括例如處理植物如噴灑在莖和葉子等等上,處理 用於植物之培養土如土壤處理等等,和處理種子如種子消 毒等等。 本發明之植物疾病防治組成物亦可以與下述之其他藥 劑摻混使用:殺真菌劑、殺蟲劑、殺蟎劑、殺線蟲劑、除 -23- 201010989 草劑、植物生長調節劑、肥料或土壤改良劑,或與彼但未 混合地同時使用。 此等其他殺真菌劑的活性成分的範例包括:唑殺真菌 的化合物如普 克 利 (propiconazole)、 丙 硫 菌 唑 (prothioconazole) 、 三 泰 隆(triadimenol)、 撲 克 拉 (prochloraz) 、 平 克 座 (penconazole) 、 得 克 利 (tebuconazole) 、 護 砂 得(flusilazole)、 達 克 利 (diniconazole) 、 溴 克 座 (bromuconazole) 、 依 普 座 (epoxiconazole)、 待 克 利 (difenoconazole)、 環 克 座 (cyproconazole) 、 滅特座(metconazole)、 賽 福 座 (triflumizole) 、 四 克 利 (tetraconazole) 、 邁 克 尼 (microbutanil) 、 芬 克 座 (fenbuconazole)、 菲 克 利 (hexaconazole)、 氟 喹 唑 (fluquinconazole)、 滅 囷 唑Wherein R1 represents the same meaning as described above. The reaction is usually carried out in the presence of a solvent. Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, MTBE, etc.; aliphatic hydrocarbons such as hexane, heptane, octane, etc.; aromatic hydrocarbons such as toluene, Xylene and the like; halogenated hydrocarbons such as chlorobenzene and the like; esters such as butyl acetate, ethyl acetate and the like; nitriles such as acetonitrile and the like; and mixtures thereof. Examples of the ruthenium used in the reaction include ruthenium metal carbonates such as sodium carbonate, potassium carbonate and the like; tertiary amines such as triethylamine, diisopropylethylamine and the like; and nitrogen-containing aromatic compounds such as Pyridine, dimethylaminopyridine, and the like. In the reaction, the compound (VII) is usually used in an amount of from 0.5 to 1 mol, based on 1 mol of the compound (IV), and the amount of the hydrazine is usually from 1 to 5 mol, based on 1 mol of the compound (IV). . The reaction temperature range of the reaction is usually from -2 ° C to 10 ° C. The reaction time for the reaction is usually in the range of from 〇1 to 24 hours. After the end of the reaction, if the solid is precipitated by adding water to the reaction mixture, the compound (V) can be isolated by filtration. If solid precipitation does not occur by adding water to the reaction mixture, the compound (V) can be isolated by extracting a mixture of the reaction mixture and water with an organic solvent, and drying the organic layer from -16 to 201010989. The isolated compound (V) can also be further purified by chromatography, recrystallization, or the like. The compounds of the invention specifically include the following compounds. N-(2-Fluoro-3-(2-propenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(2-butoxy)benzene Methyl-benzothiazole-6-carboxamide, φ N-(2-fluoro-3-(3-butoxy)phenyl)methyl-benzothiazole-6-carboxamide, N -(2-fluoro-3-(2-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(3-pentenyloxy)benzene Methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(4-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Φ N -(2-fluoro-3-(2-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(3-hexenyloxy)benzene Methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(4-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N- (2-Fluoro-3-(5-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(2-heptenyloxy)phenyl Methyl-benzothiazole-6-carboxyindole-17- 201010989 Amine, N-(2-fluoro-3-(3-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide , N-(2-Fluoro-3-(4-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-Fluoro-3 -(5-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(6-heptenyloxy)phenyl)methyl-benzo Thiazole-6-carboxyindole, N-(2-fluoro-3-(2-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3 -(3-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(4-octenyloxy)phenyl)methyl-benzo Thiazole-6-carboxamide, N-(2-fluoro-3-(5-octenyloxy)phenyl)methyl-benzothiazole-6-carboxyindole, N-(2-fluoro-3 -(6-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(7-octenyloxy)phenyl)methyl-benzo Thiazole-6-carboxamide, N-(3-(2-propenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(2-butoxy)benzene Methyl-benzothiazole-6-carboxamide, N-(3-(3-butoxy)phenyl)methyl-benzothiazole-6-carboxamide, -18- 201010989 N- (3-(2•pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(3-pentenyloxy)phenyl)methyl-benzothiazole- 6-Carboguanamine, N-(3-(4-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxylate Amine, N-(3-(2-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(3-hexenyloxy)phenyl)methyl- Benzothiazole-6-carboxamide, N-(3-(4-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(5-hexeneoxy) Phenyl)methyl-benzothiazole-6-carboxamide, 9 N-(3-(2-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N- (3-(3-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(4-heptenyloxy)phenyl)methyl-benzothiazole- 6-Carboguanamine, N-(3-(5-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(6-heptenyloxy)phenyl Methyl-benzothiazole-6-carboxamide, N-(3-(2-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(3) -octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N_(3-(4-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, φ Ν-(3·(5-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-(6-octenyloxy)phenyl)methyl-benzo Thiazol-6-carboxyguanamine, Ν-(3-(7-octenyloxy)phenyl)methyl-benzene Thiazole-6-carboxamide, Ν-(2-fluoro-3-(2-propynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν_(2-fluoro-3-( 2-butynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N_(2-.fluoro-3-(3-butynyloxy)phenyl)methylbenzothiazole- 6-Carboxylimine, -19 - 201010989 N-(2-Fluoro-3-(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-Fluoro- 3-(3-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(4-pentynyloxy)phenyl)methyl-benzene And thiazol-6-carboxyguanamine, N-(2-fluoro-3-(2-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, φ N-(2-fluoro- 3-(3-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(4-hexynyloxy)phenyl)methyl-benzene And thiazol-6-carboxyguanamine, N-(2-fluoro-3-(5-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3 -(2-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Θ N-(2-fluoro-3-(3-heptynyloxy)phenyl)methyl-benzene And spyrazole-6-carboxyguanamine, N-(2-fluoro-3-(4-heptynyloxy)phenyl)methyl-benzothiazole -6-carboxyguanamine, N-(2-fluoro-3-(5-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-() 6-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, -20- 201010989 N-(2-fluoro-3-(2-octynyloxy)phenyl)methyl- Benzothiazole-6-carboxamide, N-(2-fluoro-3-(3-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro- 3-(4-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro-3-(5-octynyloxy)phenyl)methyl-benzene And thiazol-6-carboxyguanamine, N-(2-fluoro-3-(6-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(2-fluoro- 3-(7-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(2-propynyloxy)phenyl)methyl-benzothiazole-6 - Carboxylamamine ' N-(3-(2-butynyloxy)phenyl)methyl-benzothiolan-6-carboxamide, N-(3-(3-butynyloxy)phenyl Methyl-benzothiazole-6-carboxamide, #Ν-(3·(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-( 3-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-(4-pentynyloxy)phenyl Methyl-benzothiazole-6-carboxamide, Ν-(3-(2-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-(3) -hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-(4-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine , Ν-(3-(5-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, Ν-(3-(2-heptynyloxy)phenyl)methyl-benzene And thiazol-6-carboxyguanamine, Ν-(3-(3-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, -21 - 201010989 N-(3-(4- Rf alkynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(5-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide N-(3-(6-heptynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(2-octynyloxy)phenyl)methyl-benzo Thiazole-6-carboxamide, N-(3-(3-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(4-octynyloxy) Phenyl)methyl-benzothiazole-6-carboxamide, N-(3-(5-octynyloxy)phenyl)methyl-benzothiazole-6-carboxamide, N-(3- (6-octynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine and φ N-(3-(7-octynyloxy)phenyl)methylbenzothiazole-6-carboxamide. The plant disease controlling composition of the present invention comprises the compound of the present invention and an inert carrier. Inert carriers include solid carriers, liquid carriers, and gaseous carriers. The plant disease control composition of the present invention is usually prepared into a wettable powder, a powder, and a water dispersible by further adding an auxiliary agent for a blending agent such as a surfactant, a tackifier, a dispersing agent, a stabilizer, or the like. Granules, fluids, granules, dry fluids, emulsions, aqueous liquids, oily solutions, fuming agents, aerosols, microcapsules, and the like. The plant disease control composition of the present invention comprises a compound of the present invention in a weight ratio of usually from 0.1 to 99%, preferably from 0.2 to 90%. Examples of solid carriers include clay (eg, kaolin, diatomaceous earth, synthetic hydrated oxidized sand, Fubasami clay, bentonite, and acid clay), talc, and other inorganic minerals (eg, sericite, quart powder, sulfur powder, activated carbon) Fine powders and granules of calcium carbonate and hydrated vermiculite, and the like, and examples of liquid carriers include water; alcohols (for example, methanol and ethanol), ketones (for example, acetone and methyl ethyl ketone), and aromatics. Hydrocarbons-22- 201010989 (eg, benzene, toluene, xylene, ethylbenzene, and methylnaphthalene), aliphatic hydrocarbons (eg, Zhenghexin, Huanyuan and kerosene), vinegar (eg, acetic acid B) Esters and butyl acetate), nitriles (for example, acetonitrile and isobutyronitrile), ethers (for example, diterpene and diisopropyl ether), guanamines (for example, DMF and dimethylacetamide) ), halogenated hydrocarbons (for example, dichloroethane and trichloroethylene, carbon tetrachloride) and the like. Examples of the surfactant include alkyl sulfate, alkyl sulfonate, alkyl aryl sulfonate, alkyl aryl ether and polyoxyethylenate, polyoxyethylene glycol ether (p〇iyOXyethylene) Glycol ethers), polyvalent alcohol esters, sugar alcohol derivatives, and the like. Examples of other auxiliaries for use in the blend include tackifiers and dispersants, in particular casein, gelatin, polysaccharides (for example, starch, gum arabic, cellulose derivatives and alginic acid), lignin derivatives , bentonite, sugar, synthetic water-soluble polymers (for example, polyvinyl alcohol, polyvinylpyrrolidone and polyacrylic acid), PAP (isopropyl acid phosphate), BHT (2,6-9 di-tertiary 4-methyl-phenol), BHA (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, fatty acid Or its esters and so on. The application method of the plant disease controlling composition of the present invention for controlling plant diseases includes, for example, treating plants such as spraying on stems and leaves, treating cultivated soil for plants such as soil treatment, and the like, and treating seeds such as seed disinfection, etc. Wait. The plant disease control composition of the present invention may also be blended with other agents as follows: fungicides, insecticides, acaricides, nematicides, herbicides other than -23-201010989, plant growth regulators, fertilizers Or soil amendments, or used simultaneously with but not mixed. Examples of active ingredients of such other fungicides include: oxazole fungicidal compounds such as propiconazole, prothioconazole, triadimenol, prochloraz, penconazole ), tebuconazole, flusilazole, diniconazole, bromuconazole, epoxiconazole, difenoconazole, cyproconazole, chlorpyrifos (metconazole), triflumizole, tetraconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, carbazole
(triticonazole)、比多農(bitertanol)、依滅列(imazalil)、 護汰芬(flutriafol)、砂氟哩(simeconazole)、或種菌哩 (ipconazole);環胺殺真菌化合物如芬普福 ❹ (fenpropimorph)、三得芬(tridemorph)、或苯鏽啶 (fenpropidin);苯並咪唑殺真菌化合物如貝芬替 (carbendazim)、免賴得(benomyl)、腐絕(thiabendazole)、 或甲基多保 淨(thiophanate-methyl); 撲 滅 寧 (procymidone) ; 賽普洛(cyprodinil); 派 美 尼 (pyrimethanil) ; 乙黴威(diethofencarb) ; 秋 蘭 姆 (thiuram);扶吉胺(fiuazinain)、萬得生(mancozeb) :依普 同(iprodione); 免克寧(vinclozolin)、四 氯異 苯 腈 -24- 201010989 (chlorothalonil) ;克菌丹(captan); 滅 派 林 (m ep anipyrim) 、 拌種略(fenpiclonil); 護 汰 寧 (fludioxonil);益發靈(dichlofluanid);福爾培(folpet); 克收欣(kresoxim-methyl);亞托敏(azoxystrobin);三氟敏 (trifloxystrobin);氟嚼菌酯(fluoxastrobin);陡氧菌醋 (picoxystrobin);百克敏(pyraclostrobin);酸菌胺 (dimoxystrobin) ; pyribencarb ; 苯 氧菌胺 (metominostrobin);嫌聘菌醋(enestroburin);葚孢菌素 (spiroxamine) ;快 諾 芬 (quinoxyfen) ; rm. 壞 醯 菌 胺 (fenhex amid) ; 凡 殺 同 (famoxadone) ; 咪 唑 菌 酮 (fenamidone);座賽胺(zoxamide);噻唑菌胺(etaboxam); 引哩磺菌胺(amisulbrom);丙森鋅(iprovalicarb);苯噻菌 胺(benthiavalicarb);賽座滅(cyazofamid);雙炔醯菌胺 (mandipropamid);白克歹 IJ (boscalid) ; Pj± 噻菌胺 (penthiopyrad);滅芬農(metrafenone);氟耻菌藤胺 ❹ (fluopyram) ; bixafen ;環氟菌胺(cyflufenamid);丙氧喹 啉(proquinazid);聘醚菌胺(orysastrobin);福拉比 (furametpyr);賽氟滅(thifluzamide);滅普寧(mepronil); 福多寧(flutolanil);氟硫滅(flusulfamide);氟耻菌胺 (fluopicolide);右滅達樂(metalaxyl Μ) ; kiralaxyl ;福賽 得(fosetyl);克絕(cymoxanil);賓克隆(pencycuron):脫 克松(tolclofos-methyl);加普胺(carpropamid);雙氯氰菌 胺(diclocymet) ;氰菌胺(fenoxanil); :三 賽 唑 (tricyclazole) ; 百快隆(pyroquilon); 撲 殺 熱 -25- 201010989 (probenazole);異噻菌胺(isotianil);噻醒菌胺 (tiadinil) : tebufroquin ;達滅淨(diclomezine);嘉賜黴素 (kasugamycin);富米綜(ferimzone);熱必斯(fthalide); 維利徽素(validamycin);羥基異噚唑;雙胍辛胺乙酸鹽 (iminoctadin-acetate);亞賜圃(isoprothiolane);歐索林酸 (oxo丨inic acid);氧四環素(oxytetracycline);鏈黴素; sedaxane ; isopyrazam ; BAF-14182 ; flutianil ;驗性氣化 銅;氫氧化銅(II);鹼性硫酸銅;有機銅;和硫。 _ 殺蟲劑的活性成分的範例包括下面化合物= (1)有機磷化合物 毆殺松(acephate)、磷化銘、butathiofos、硫線磷 (cadusafos) 氯氧鱗(chlorethoxyfos)、克芬松 (chlorfenvinphos)、陶斯松(chlorpyrifos)、甲基陶斯松 (chlorpyrifos-methyl)、氰乃松(cyanophos): CYAP、大利 松(diazinon)、DCIP(二氯二異丙基醚)、除線磷 (dichlofenthion) : ECP、二氯松(dichlorvos) : DDVP、大 ❿ 滅松(dimethoate)、甲基毒蟲畏(dimethylvinphos)、二硫 松(disulfoton) 、 E P N 、愛殺(ethion)、普伏松 (ethoprophos)、益多松(etrimfos)、芬殺松(fenthion): MPP' 撲滅松(fenitrothion): MEP、福賽絕(fosthiazate)、 福木松(formothion)、磷化氫、亞芬松(isofenphos)、加福 松(isoxathion)、馬拉松(malathion)、mesulfenfos、滅大 松(methidathion): DMTP、亞素靈(monocrotophos)、乃力 松(naled) : BRP、異亞磷(oxydeprofos) : ESP、巴拉松 -26- 201010989 (parathion)、裕必松(phosalone)、益滅松(phosmet): PMP 、亞特松(pirimiphos-methyl)、必芬松 (pyridafenthion)、拜裕松(quinalphos)、賽達松 (phenthoate) : PAP、佈飛松(profenofos)、加護松 (propaphos)、普硫松(prothiofos)、白克松(pyraclorfos)、 殺力松(salithion)、硫丙磷(sulprofos)、丁基嘧啶磷 (tebupirimfos)、亞培松(temephos)、殺蟲畏 謇(tetrachlorvinphos)、托福松(terbufos) ' 硫滅松 (thiometon) ' 三氯松(trichlorphon) : DEP、繁米松 (vamidothion)、福瑞松(phorate)、硫線磷(cadusafos)等 等; (2)胺甲酸酯化合物 棉鈴威(alanycarb)、免敵克(bendiocarb)、免扶克 (benfuracarb)、BPMC、加保利(carbaryl)、加保扶 (carbofuran)、丁基加保扶(carbosulfan)、除線威 〇 (cloethocarb)、愛芬克(ethiofencarb)、丁基滅必蟲 (fenobucarb) 、 芬硫 克 (fenothiocarb) 、 芬 諾 克 (fenoxycarb) 、 呋線 威 (furathiocarb) 、 異 丙 威 (isoprocarb) :MIPC 、 治 滅蟲(metolcarb) 、納 乃 得 (methomyl)、滅賜克(methiocarb)、NAC、殿殺滅 (oxamyl)、比力口普(pirimicarb)、安丹(propoxur) : PHC ' XMC、硫敵克(thiodicarb)、滅爾蟲(xylylcarb)、得滅克 (aldicarb)等等; (3)合成的除蟲菊酯化合物 -27- 201010989 阿納寧(acrinathrin)、亞烈寧(allethrin)、拜富寧 (b enfluthrin) 、β_赛 扶 (beta-cyfluthrin)、 畢 芬 (bifenthrin)、 乙氰菊酯(cycloprothrin)、賽扶寧 、賽洛寧 (cyhalothrin) 、 賽 滅 寧 (cypermethrin) 、 第 滅 寧 (deltamethrin) 、益 化 利 (esfenvalerate) 、 依 芬 寧 (ethofenprox) 、芬 普 寧 (fenpropathrin) 、 芬 化 利 (fenvalerate)、護賽寧(flucythrinate)、flufenoprox、氟氯 苯菊醋(flumethrin)、福化利(fluvalinate)、合芬寧 _ (halfenprox)、依普寧(imiprothrin)、百滅寧 (p.ermethrin)、普亞列寧(prallethrin)、除蟲菊精 (pyrethrins)、列滅寧(resmethrin)、σ-賽滅寧(sigma-cypermethrin) 砂護芬(silafluofen)、七氟菊醋 (tefluthrin)、泰滅寧(tralomethrin)、拜富寧 (transfluthrin)、治滅寧(tetramethrin)、酷丁滅蟲 (phenothrin)、賽酚寧(cyphenothrin)、α-賽滅寧(alpha-cypermethrin)、ζ-賽滅寧(zeta-cypermethrin)、λ-賽洛寧 ❿ (lambda-cyhalothrin)、呋喃菊酯(furamethrin)、τ-福化利 (tau-f.luvalinate)、2,3,5,6 -四氟-4-(甲氧基甲基)苯甲基 (EZ)-(IRS, 3RS; IRS, 3SR)-2,2-二甲基-3-丙-1-烯基環丙 烷羧酸酯、2,3,5,6-四氟-4-甲基苯甲基(EZ)-(IRS,3RS ; 1RS,3SR)-2,2-二甲基-3-丙-1-烯基環丙烷羧酸酯、 2,3,5,6-四氟-4-(甲氧基甲基)苯甲基(1RS,3RS; 1RS, 3SR)-2,2-二甲基-3-(2-甲基-1-丙烯基)環丙烷羧酸酯等 等; •28- 201010989 (4) 沙蠶毒素化合物 培丹(cartap)、免速達(bensultap)、硫賜安 (thiocyclam)、殺蟲單(monosultap)、殺蟲雙(bisultap)等 等; (5) 新尼古丁類化合物 益達胺(imidacloprid)、稀蟲靈(nitenpyram)、亞滅培 (acetamiprid) 賽速安(thiamethoxam)、賽果培 • (thiacloprid)、達特南(dinotefuran)、可尼丁(clothianidin) 等等; (6) 苯甲醯脲化合物 克福隆(chlorfluazuron)、雙三氟蟲脲(bistrifluron)、 汰芬隆(diafenthiuron)、二福隆(diflubenzuron)、陡蜱 (fluazuron)、 氣 環(flucycloxuron)、氟 芬隆 (flufenoxuron) 六伏隆(hexaflumuron)、祿芬隆 (lufenuron)、 諾 伐 隆(novaluron)、 多 氣 脲 粵 (noviflumuron)、得福隆(teflubenzuron)、三福隆 (triflumuron)、triazlon 等等; (7) 苯基吡唑化合物 乙醯蟲腈(acetoprole)、乙蟲清(ethiprole)、芬普尼 (fipronil)' vaniliprole、 pyriprole ' pyrafluprole 等等; (8) 內毒蛋白(Bt toxin)殺蟲劑 衍生自蘇力菌(Bacillus thuringiensis)之新鮮孢子、 由蘇力菌所產生之結晶狀毒素、和其混合物; (9) 肼化合物 -29- 201010989 可芬諾(chromafenozide)、合芬隆(halofenozide)、滅 芬諾(methoxyfenozide)、得芬諾(tebufenozide)等等; (1〇)有機氯化合物 艾氏劑(aldrin)、地特靈(dieldrin)、得氯蟎 (dienochlor) 安殺番(endosulfan)、氯化甲醇 (methoxychlor)等等;(triticonazole), bitertanol, imazalil, flutriafol, simeconazole, or ipconazole; a cyclic amine fungicidal compound such as fenfluz ( Fenpropimorph), tridemorph, or fenpropidin; benzimidazole fungicidal compounds such as carbendazim, benomyl, thiabendazole, or methylpoly Thiophanate-methyl; procymidone; cyprodinil; pyrimethanil; diethofencarb; thiuram; fiuazinain, wande (mancozeb): iprodione; vinclozolin, tetrachloroisophthalonitrile-24- 201010989 (chlorothalonil); captan; capprine (m ep anipyrim), seed dressing Fenpiclonil; fludioxonil; dichlofluanid; folpet; kresoxim-methyl; azoxystrobin; trifloxystrobin; Fluoxastrobin; steep oxygen bacteria vinegar (pi Coxystrobin); pyraclostrobin; dimoxystrobin; pyribencarb; metomycin (metominostrobin); enestroburin; spiroxamine; quinoxyfen; Fenhex amid; famoxadone; fenamidone; zoxamide; etaboxam; amisulbrom; propidium zinc Iprovalicarb); benthiavalicarb; cyazofamid; mandipropamid; boscalid; Pj± penthiopyrad; metrafenone Fluopyram; bixafen; cyflufenamid; proquinazid; oressastrobin; furametpyr; thifluzamide ; mepronil; fluolanil; flusulfamide; fluopicolide; metalaxyl ;; kiralaxyl; fosetyl; Cymoxanil); pencycuron: tolclofos-methyl ; carpropamid; diclocymet; fenoxanil; tricyclazole; pyroquilon; culling fever-25- 201010989 (probenazole); Isodinil; tiadinil: tebufroquin; diclomezine; kasugamycin; ferimzone; fthalide; (validamycin); hydroxyisoxazole; dioctyloctylamine acetate (iminoctadin-acetate); isoprothiolane; oxo丨inic acid; oxytetracycline; streptomycin; Isopyrazam; BAF-14182; flutianil; analytical copper oxide; copper (II) hydroxide; basic copper sulfate; organic copper; Examples of active ingredients of insecticides include the following compounds = (1) organophosphorus compounds acephate, phosphating, butathiofos, cadusafos, chlorethoxyfos, chlorfenvinphos ), chlorpyrifos, chlorpyrifos-methyl, cyanophos: CYAP, diazinon, DCIP (dichlorodiisopropyl ether), depletion of phosphorus (dichlofenthion): ECP Dichlorvos: DDVP, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, benefit Etrimfos, fenthion: MPP' fenitrothion: MEP, fosthiazate, formothion, phosphine, isofenphos, plusfusone (isoxathion), marathion (maathion), mesulfenfos, methadinion: DMTP, monocrotophos, naled: BRP, oxydeprofos: ESP, balason-26- 201010989 (parathion), Yubi Phosalone, phosmet: PMP, pirimiphos-methyl, pyridafenthion, quinalphos, phenthoate: PAP, profenofos ), propaphos, prothiofos, pyraclorfos, salithion, sulprofos, tebupirimfos, temephos, kill Tetrachlorvinphos, terbufos 'thiometon ' trichlorphon : DEP, vamidothion, phorate, cadusafos, etc.; (2) urethane compound alanycarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbofuran, carbosulfan ), cloethocarb, ethiofencarb, fenobucarb, fenothiocarb, fenoxycarb, furathiocarb, isoprocarb (isoprocarb) : MIPC, treatment of pest control Metocarb), metomyl, metiocarb, NAC, oxamyl, pirimicarb, propoxur: PHC 'XMC, thiodicarb , xylylcarb, aldicarb, etc.; (3) synthetic pyrethroid compounds -27- 201010989 aninin (acrinathrin), arrhenone (allethrin), befunning (b enfluthrin , β_cyfluthrin, bifenthrin, cycloprothrin, cyprofen, cyhalothrin, cypermethrin, deltamethrin , esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, flucythrinate, flufenoprox, flumethrin, fuhuali Fluvalinate, halfenprox, imiprothrin, p.ermethrin, prallethrin, pyrethrins, resmethrin, σ- Sigma-cypermethrin Afluofen), tefluthrin, trolomethrin, transfluthrin, tetramethrin, phenothrin, cyphenothrin, alpha-race Alpha-cypermethrin, zeta-cypermethrin, lambda-cyhalothrin, furamethrin, tau-f.luvalinate , 2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl (EZ)-(IRS, 3RS; IRS, 3SR)-2,2-dimethyl-3-propan- 1-alkenylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4-methylbenzyl (EZ)-(IRS, 3RS; 1RS, 3SR)-2,2-dimethyl- 3-prop-1-enylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl (1RS, 3RS; 1RS, 3SR)-2,2 - dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, etc.; •28- 201010989 (4) Neretic toxin compound cartap, free speed (bensultap), sulfur Thiocyclam, monosultap, bisultap, etc.; (5) new nicotine compounds imidacloprid, nitenpyram, aceta Miprid) thiamethoxam, thiacloprid, dinotefuran, clothianidin, etc.; (6) Benzamidine urea compound chlorfluazuron, double three Bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron hexaflumuron, lufenlong Lufenuron), novaluron, noviflumuron, teflubenzuron, triflumuron, triazlon, etc.; (7) phenylpyrazole compound acetaminophen (acetoprole) ), ethiprole, fipronil 'vaniliprole, pyriprole 'pyrafluprole, etc.; (8) Bt toxin insecticide derived from fresh spores of Bacillus thuringiensis, Crystalline toxin produced by S. cerevisiae, and mixtures thereof; (9) Hydrazine compound -29- 201010989 Chromofenozide, halofenozide, methoxyfenozide, tebufenoz Ide), etc.; (1) organochlorine compounds Aldrin, dieldrin, dienochlor, endosulfan, methoxychlor, etc.
(1 1)天然殺蟲劑 機械油和菸鹼硫酸鹽;和 (12)其他殺蟲劑(1) natural insecticides, mechanical oils and nicotine sulfates; and (12) other pesticides
阿維菌素- B(avermectin-B)、新殺摘(bromopropylate) 、布芬淨(buprofezin)、克凡派(chlorphenapyr)、賽滅淨 (cyromazine)、D-D(l,3-二氯丙稀)、因滅汀(emamectin- benzoate) 、 芬 殺蟎 (fenazaquin) 、 批 氟 硫 磷 (flupyrazofos)、 稀蟲乙醋(hydroprene)、 美 賜 平 (methoprene) 、 因得 克 (indoxacarb) 、 惡 蟲 酮 (metoxadiazone) 、犬心 安(milbemy cin-A)、 派 滅 淨 (pymetrozine)、 陡蟲丙 醚(pyridalyl)、百 利 普 芬 (pyriproxyfen) 、 賜諾 殺(spinosad)、 氟 蟲 胺 (sulfluramid) 、 脫芬 瑞(tolfenpyrad)、 唑 蚜 威 (triazamate)、氟蟲醯胺(flubendiamide)、lepimectin、砷 酸、benclothiaz、氰胺化鈣、多硫化鈣、可氯丹 (chlordane) 、 DDT 、 DSP 、 flufenerim 、氟尼胺 (flonicamid)、flurimfen、覆滅彌(formetanate)、安百敏 (metam-ammonium)、威百敢(metam-sodium)、溴化甲院、 -30- 201010989 nidinotefuran、油酸押、protrifenbute、螺甲觸酯 (spiromesifen)、硫、美氟綜(metaflumizone)、螺蟲乙醋 (spirotetramat)、pyrifluquinazone、spinetoram、及勉安 勃(chlorantraniliprole)和 cyantraniliprole 。 殺蟎劑的活性成分的範例包括亞醌蟎(acequinocyl) _、 三亞滿(amitraz)、西脫觸(benzoximate)、聯苯肼醋 (bifenaate)、新殺蟎(bromopropyl ate)、蟎離丹 春 (chinomethionat)、克氯苯(chlorobenzilate)、CPCBS (殺 蟎酯(chlorfenson))、克芬螨(clofentezine)、賽芬蠘 (cyflumetofen)、開樂散(kelthane)(大克織(dicofol))、依 殺蟎(etoxazole)、芬佈賜(fenbutatin oxide)、芬硫克 (fenothiocarb)、芬普織(fenpyroximate)、嘧織醋 (fluacrypyrim)、fluproxyfen、合赛多(hexythiazox) ' 殿織 多(propargite) ·· BPPS、殺摘黴素(polynactins)、畢達本 (pyridaben)、畢汰芬(Pyrimidifen)、得芬瑞 β (tebufenpyrad)、得脫踊(tetradifon)、賜派芬 (spirodiclofen)、螺甲摘醋(spiromesifen)、螺蟲乙酯 (spirotetramat)、amidoflumet、和 cyenopyrafen ° 殺線蟲劑的活性成分的範例包括 DCIP、福賽絕 (fosthiazate)、左咪哇鹽酸(levamisol hydrochloride)、甲 基異硫氰酸鹽;摩朗得酒石酸鹽(moraltel tartarate)、和 imicyafos 。 本發明之植物疾病防治方法具有施加有效量之本發明 化合物至植物或土壤之步驟。本發明之防治方法通常藉由 -31 - 201010989 施加本發明之植物疾病防治組成物至植物或土壤而予以進 行。 當於本發明之植物疾病防治方法中,本發明之植物疾 病防治組成物的用量依據天氣條件、調製形式、施加期 間、施加方法、施加位置、標的疾病、標的作物等等而變 化,且本發明之植物疾病防治組成物中本發明化合物的含 量通常爲1至500 g(較佳地爲2至200 g)/1 000 m2。乳 劑、可濕性粉劑、流性物等等通常在施用前用水稀釋,且 @ 於此案例中,稀釋後,本發明化合物的濃度通常爲0.0005 至2重量%,較佳地爲〇.〇〇5至1重量%,而粉劑、顆粒 等等通常未稀釋即予以使用。於處理種子中,本發明之植 物疾病防治組成物中之本發明化合物的含量通常爲0.001 至100 g’較佳地爲0.01至50 g,基於1 kg的種子計。 本發明之植物疾病防治組成物可以作爲農用土地如田 野、稻田、泥炭、果樹園等等之植物疾病之防治組成物。 本發明之植物疾病防治組成物能防治或預防由用於培養下 參 面"農作物"之作物土地中之植物疾病所引起的植物疾病。 農作物:玉米、稻米、小麥、大麥、黑麥、燕麥、高 梁、棉花、黃豆、花生、蒿麥、甜菜、油菜子、向日葵、 甘蔗、菸草等等;蔬菜:茄子科蔬菜(茄子、番茄、甜 椒、胡椒、馬鈴薯等等)、瓜類蔬菜(黃瓜、南瓜、筍瓜、 西瓜、香瓜等等)、十字花科蔬菜(日本小紅蘿蔔、白蕪 菁、辣根、球莖甘藍、大白菜'高麗菜、芥菜、青花菜、 花椰菜等等)、菊科蔬菜(牛蒡、茼蒿、朝鮮薊、萵苣等 -32- 201010989 等)、百合科蔬菜(蔥、洋蔥、大蒜、和蘆荀)、 ammiaceous蔬菜(胡蘿蔔、香序、斧菜、歐洲蘿蔔等等)、 藜科蔬菜(菠菜、瑞士慕菜等等)、薄荷科蔬菜(紫蘇、薄 荷、羅勒等等)、草莓、甘藷、日本薯蕷、芋等等, 花; 觀葉植物; 水果:鑛果類水果(鑛果、梨、日本梨、木瓜、梓等 參等)、核果類(stone fleshy fruits)(桃、洋李(pium)、油 桃、梅(Prunus mume)、櫻桃、杏仁、梅子等等)、柑橘屬 水果(蜜柑、柳橙、檸檬、rime、葡萄柚等等)、核果類 (nuts)(栗子、胡桃、榛子、杏仁、開心果、腰果、澳洲胡 桃果仁等等)、莓果(藍莓、蔓越莓、黑莓、覆盆子等 等)、葡萄、柿、橄欖、枇杷、香蕉、咖啡、棗椰子、椰 子等等, 非水果樹的其他樹木:茶、桑椹、顯花植物、行道樹 ❹ (白蠟樹、樺、山茱萸屬、桉樹類、銀杏、紫丁香、楓 木、櫟屬、白楊木、猶大樹、楓香、平面樹、櫸樹'金鐘 柏、冷杉木、鐵杉、杜松、松屬、雲杉屬、和紅豆杉)等 等。 前述"作物"包括已藉由典型的育種法或基因工程技術 而對下述者具有抗性之作物:HPPD抑制劑如異惡唑草酮 (isoxaflutole)、ALS 抑制劑如咪草煙(imazethapyr)或吩磺 隆(thifensulfuron-methyl)、EPSP合成酶抑制劑、麩醯胺 酸合成酶抑制劑、和除草劑如溴苯腈(bromoxynil)。 -33- 201010989 藉由典型的育種法而有抗性之"作物"的範例包括對咪 唑啉酮除草劑如imazethapyr具有抗性之Clearfield (註冊 商標)canola、和對磺醯脲 ALS抑制除草劑如 thifensulfuron -甲基具有抗性之STS黃S。另外’藉由基 因重組而有抗性之"作物"的範例包括對草甘膦或固殺草 (g 1 u f 〇 s i n a t e)有抗性之玉米變種。此等玉米變種已以產品 名如”RoundupReady(註冊商標)"和"LibertyLink(註冊商 標)"在市場上銷售。 _ 前述”作物”包括使用此基因重組技術所產生的基因工 程作物,其例如能合成芽孢桿菌屬中已知的選擇性毒素。 於此等基因工程作物中所表現之毒素的範例包括:衍 生自臘狀桿菌(Bacillus cereus)或甲蟲芽孢桿菌(Bacillus popilliae)之殺蟲蛋白質;衍生自蘇立菌之 δ-內毒素如 CrylAb 、 Cry 1 Ac ' Cry 1 F ' Cry 1 F a2、Cry2Ab、Cry3A、 Cry3Bbl 或 Cry9C ;殺蟲蛋白質如 VIP1、VIP2、VIP3、 或VIP3A ;衍生自線蟲類之殺蟲蛋白質;經由動物所產生 參 之毒素如蠍子毒素、蜘蛛毒素、蜜蜂毒素、或特定昆蟲神 經毒素;絲狀菌毒素;植物凝集素;凝集素;蛋白酶抑制 劑如胰蛋白酶抑制劑、絲胺酸蛋白酶抑制劑、儲存性蛋白 質(patatin)、硫氫蛋白晦抑制劑(cystatin)、或木瓜酶抑制 劑;核酿體去活性蛋白質(ribosome-inactivating proteins)(RIP) 如賴胺酸、玉米-RIP、相思子素、 luffin、肥官草毒素(saporin)、或briodin ;類固醇新陳代 謝酶如3-羥基類固醇氧化酶、脫殼類固醇-UDP-葡萄糖苷 -34- 201010989 基轉移酶(e c d y s t e r 〇 i d - U D P - g 1 u c 〇 s y 1 t r a n s f e r a s e )、或膽固 醇氧化酶;脫皮素抑制劑;hmg-coa還原酶;離子通道 抑制劑如鈉通道抑制劑或鈣通道抑制劑;青春激素酯酶; 利尿激素受體;芪合成酶;聯苯甲基合成酶;殼質酶;和 聚葡萄糖酶。 此外,於此等基因重組作物中表現之毒素亦包括:δ-內毒素蛋白質如 CrylAb、CrylAc、CrylF、CrylFa2、 φ Cry2Ab、Cry3A、Cry3Bbl 或 Cry9C 和殺蟲蛋白質如 VIP1、VIP2、VIP3或VIP3A的混成毒素;部分刪除的毒 素;和改質的毒素。此等混成毒素係使用基因重組技術而 由此等蛋白質之不同區域的新組合而產生的。已知含有刪 除部分胺基酸序列之CrylAb作爲部分刪除的毒素。改質 的毒素係藉由天然毒素的一或多種胺基酸的取代作用而產 生的。 此等毒素和能合成此等毒素之重組植物的範例被描述 ❼於 EP-A-0 3 74 753、WO 93/07278、WO 95/34656、EP-A-0 427 529、EP-A-45 1 878、W Ο 0 3 / 0 5 2 0 7 3 等等。 此等重組植物所含之毒素能使植物對特別屬於 Coleoptera、 Diptera 和 Lepidoptera 之昆蟲害蟲提供抗 性。 再者,已知包括一或多種殺昆蟲害蟲抗性基因基且表 現一或多種毒素之基因重組植物,且一些此等基因重組植 物已在市場上銷售。此等基因重組植物的範例包括 YieldGard (註冊商標)(表現CrylAb毒素之玉米變種)、 -35- 201010989Avermectin-B, bromopropylate, buprofezin, chlorphenapyr, cyromazine, DD (l,3-dichloropropene) ), emamectin- benzoate, fenazaquin, flupyrazofos, hydroprene, metoprene, indoxacarb, worm Ketone (metoxadiazone), milbemy cin-A, pymetrozine, pyridalyl, pyriproxyfen, spinosad, sulfluramid , tolfenpyrad, triazamate, flubendiamide, lepimectin, arsenic acid, benclothiaz, calcium cyanamide, calcium polysulfide, chlordane, DDT, DSP, Flufenerim, flonicamid, flurimfen, formetanate, metam-ammonium, metam-sodium, bromide, -30- 201010989 nidinotefuran, oily acid, Protrifenbute, spironolactone (spiro) Mesifen), sulfur, metaflumizone, spirotetramat, pyrifluquinazone, spinetoram, and chlorantraniliprole and cyantraniliprole. Examples of active ingredients of acaricides include acequinocyl _, amitraz, benzoximate, bifenaate, bromopropyl ate, and diarrhea (chinomethionat), chlorobenzilate, PCBS (chlorfenson), clofentezine, cyflumetofen, kelthane (dicofol), According to etoxazole, fenbutatin oxide, fenothiocarb, fenpyroximate, fluacrypyrim, fluproxyfen, hexythiazox 'propagite · · · BPPS, polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, snail Examples of active ingredients of spiromesifen, spirotetramat, amidoflumet, and cyenopyrafen ° nematicides include DCIP, fosthiazate, levamisol hydrochloride, methyl isoform Thiocyanate ; Molang obtained tartrate (moraltel tartarate), and imicyafos. The method for controlling plant diseases of the present invention has the step of applying an effective amount of the compound of the present invention to plants or soil. The control method of the present invention is usually carried out by applying the plant disease control composition of the present invention to plants or soil by -31 - 201010989. In the method for controlling plant diseases of the present invention, the amount of the plant disease controlling composition of the present invention varies depending on weather conditions, a modulation form, an application period, an application method, an application position, a target disease, a target crop, and the like, and the present invention The compound of the present invention is usually contained in the plant disease controlling composition in an amount of from 1 to 500 g (preferably from 2 to 200 g) / 1 000 m2. Emulsions, wettable powders, fluids and the like are usually diluted with water before application, and @ In this case, the concentration of the compound of the present invention after dilution is usually from 0.0005 to 2% by weight, preferably 〇.〇〇. 5 to 1% by weight, while powders, granules and the like are usually used without being diluted. In the treatment of the seed, the compound of the present invention in the plant disease controlling composition of the present invention is usually contained in an amount of from 0.001 to 100 g', preferably from 0.01 to 50 g, based on 1 kg of the seed. The plant disease control composition of the present invention can be used as a control composition for plant diseases of agricultural land such as fields, rice fields, peats, orchards, and the like. The plant disease controlling composition of the present invention can prevent or prevent plant diseases caused by plant diseases used in cultivating the crop land of the "grass" "crop". Crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, artemisia, beets, rapeseed, sunflower, sugar cane, tobacco, etc.; vegetables: eggplant vegetables (eggplant, tomato, sweet) Pepper, pepper, potato, etc.), melon vegetables (cucumber, pumpkin, winter squash, watermelon, cantaloupe, etc.), cruciferous vegetables (Japanese small carrots, white phthalocyanine, horseradish, stalk cabbage, Chinese cabbage) Vegetables, mustard, broccoli, broccoli, etc.), chrysanthemum vegetables (burdock, chrysanthemum, artichoke, lettuce, etc. -32- 201010989, etc.), liliaceae vegetables (onions, onions, garlic, and reeds), ammiaceous vegetables ( Carrots, incense, axe, European radish, etc.), leeks (spinach, swiss, etc.), mint vegetables (perilla, mint, basil, etc.), strawberries, sweet potatoes, Japanese yam, oysters, etc. , flower; foliage plant; fruit: mineral fruit (mineral fruit, pear, Japanese pear, papaya, medlar, etc.), stone fleshy fruits (peach, plum (pium), nectarine, Prunus mume, cherries, almonds, plums, etc.), citrus fruits (citrus, orange, lemon, rime, grapefruit, etc.), nuts (nuts) (chessnuts, walnuts, hazelnuts, almonds, pistachios) , cashew nuts, Australian walnut nuts, etc.), berries (blueberries, cranberries, blackberries, raspberries, etc.), grapes, persimmons, olives, alfalfa, bananas, coffee, date palms, coconuts, etc., non-fruit trees Other trees: tea, mulberry, flowering plants, street trees (ash, birch, hawthorn, eucalyptus, ginkgo, lilac, maple, eucalyptus, aspen, jude, maple, plane tree, dragonfly Trees 'Thuja, fir, hemlock, juniper, pinus, spruce, and yew) and so on. The aforementioned "Crops" include crops that have been rendered resistant by typical breeding or genetic engineering techniques: HPPD inhibitors such as isoxaflutole, ALS inhibitors such as imazethapyr ( Imazethapyr) or thifensulfuron-methyl, an EPSP synthase inhibitor, a branamine synthase inhibitor, and a herbicide such as bromoxynil. -33- 201010989 Examples of "crops" that are resistant by typical breeding methods include Clearfield (registered trademark) canola, which is resistant to imidazolinone herbicides such as imazethapyr, and weed suppression to sulfonamide ALS An agent such as thifensulfuron-methyl is resistant to STS yellow S. In addition, examples of "crops" that are resistant by genetic recombination include maize varieties that are resistant to glyphosate or g 1 u f 〇 s i n a t e. Such corn varieties have been marketed under the product names such as "RoundupReady (registered trademark) " and "LibertyLink (registered trademark)" _ The aforementioned "crop" includes genetically engineered crops produced using this genetic recombination technique, It can, for example, synthesize selective toxins known in the genus Bacillus. Examples of toxins expressed in such genetically engineered crops include insecticides derived from Bacillus cereus or Bacillus popilliae. Protein; δ-endotoxin derived from S. serrata such as CrylAb, Cry 1 Ac ' Cry 1 F ' Cry 1 F a2, Cry2Ab, Cry3A, Cry3Bbl or Cry9C; insecticidal proteins such as VIP1, VIP2, VIP3, or VIP3A; Insecticidal protein from nematodes; toxins produced by animals such as scorpion toxin, spider toxin, bee toxin, or specific insect neurotoxin; filamentous toxin; plant lectin; lectin; protease inhibitor such as trypsin inhibition Agent, serine protease inhibitor, patatin, cystatin, or papain inhibition Ribosome-inactivating proteins (RIP) such as lysine, corn-RIP, acacia, luffin, saporin, or briodin; steroid metabolism enzymes such as 3-hydroxyl Steroid oxidase, hull steroid-UDP-glucoside-34- 201010989 ecdyster 〇id - UDP - g 1 uc 〇sy 1 transferase , or cholesterol oxidase; ecdysone inhibitor; hmg-coa reductase Ion channel inhibitors such as sodium channel inhibitors or calcium channel inhibitors; vasopressin esterase; diuretic hormone receptor; purine synthase; biphenylmethyl synthase; chitinase; and polyglucose. Toxins expressed in isogenic crops include: δ-endotoxin proteins such as CrylAb, CrylAc, CrylF, CrylFa2, φ Cry2Ab, Cry3A, Cry3Bbl or Cry9C and insecticidal proteins such as VIP1, VIP2, VIP3 or VIP3A; Deleted toxins; and modified toxins. These mixed toxins are produced using genetic recombination techniques and thus new combinations of different regions of the protein. Remove some CrylAb known to contain the amino acid sequence of a partial deletion of the toxin. Modified toxin-based one or more amino acid substitutions generated by the action of the native toxin. Examples of such toxins and recombinant plants capable of synthesizing such toxins are described in EP-A-0 3 74 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-45 1 878, W Ο 0 3 / 0 5 2 0 7 3 and so on. The toxins contained in these recombinant plants enable plants to provide resistance to insect pests particularly belonging to Coleoptera, Diptera and Lepidoptera. Further, genetically recombinant plants comprising one or more insecticidal pest resistance gene groups and exhibiting one or more toxins are known, and some of these genetically recombinant plants are commercially available. Examples of such genetically modified plants include YieldGard (registered trademark) (a variant of maize expressing CrylAb toxin), -35- 201010989
YieldGard Rootworm (註冊商標)(表現Cry3Bbl毒素之玉 米變種)、YieldGard Plus (註冊商標)(表現CrylAb和 Cry3Bbl毒素之玉米變種)、Herculex I (註冊商標)(表現 phosphinotricine N-乙酸基轉移酶(PAT)以便對CrylFa2毒 素和草丁憐(gluphosinate)具有抗性之玉米變種)、 NuCOTN33B (表現Cry 1 Ac毒素之棉花變種)、Bollgard I (註冊商標)(表現CrylAc毒素之棉化變種)、Bollgard II (註冊商標)(表現CrylAc和Cry2Ab毒素之棉化變種)、 _ VIPCOT (註冊商標)(表現 VIP毒素之棉化變種)、 NewLeaf (註冊商標)(表現Cry3A毒素之馬鈴薯變種)、 NatureGard (註冊商標)、Agrisure (註冊商標)、GT Advantage (GA21抗草甘膦特性)、Agrisure (註冊商標)、 CB Advantage (Btll 玉米螟(CB)特性)、和 Protecta (註冊 商標)。 前述"作物”亦包括使用基因工程技術所產生之作物,YieldGard Rootworm (registered trademark) (a maize variety showing Cry3Bbl toxin), YieldGard Plus (registered trademark) (a maize variety showing CrylAb and Cry3Bbl toxin), Herculex I (registered trademark) (expressing phosphinotricine N-acetoxytransferase (PAT) For maize varieties resistant to CrylFa2 toxin and gluphosinate, NuCOTN33B (a cotton variety showing Cry 1 Ac toxin), Bollgard I (registered trademark) (a cotton variant showing CrylAc toxin), Bollgard II ( Registered trademark) (expressing cotton varieties of CrylAc and Cry2Ab toxins), _ VIPCOT (registered trademark) (presenting cotton varieties of VIP toxins), NewLeaf (registered trademark) (potato varieties expressing Cry3A toxin), NatureGard (registered trademark) , Agrisure (registered trademark), GT Advantage (GA21 glyphosate resistant), Agrisure (registered trademark), CB Advantage (Btll corn glutinous (CB) characteristics), and Protecta (registered trademark). The aforementioned "crop" also includes crops produced using genetic engineering techniques.
其能產生具有選擇作用之抗病原性物質。 G 已知PR蛋白質等等作爲此等抗病原性物質(PRPs、 EP_A-0 392 225)。產生彼之此等抗病原性物質和基因重組 作物被描述於 ΕΡ-Α-0 392 225、WO 95/3 3 8 1 8、ΕΡ-Α-0 353 191 等等。 基因重組作物中所表現之此等抗病原性物質的範例包 括:離子通道抑制劑如鈉通道抑制劑或鈣通道抑制劑(已 知KP1、KP4和KP6毒素等等,其係藉由病毒而產生 的);芪合成酶;聯苯甲基合成酶;甲殼素酶;聚葡萄糖 -36- 201010989 酶;PR蛋白質;和由微生物所產生之抗病原性物質如肽 抗生素、具有雜環之抗生素、與植物疾病抗性有關的蛋白 質因數(其稱爲植物疾病抗性基因且被描述於 WO 03/000906)。 作爲可以藉由本發明化合物防治之植物疾病,例如, 由絲狀菌所引起的植物疾病被提及。更具體的範例包括但 不限於下面疾病。 〇 本發明之植物疾病防治方法通常係藉由依據上述施加 本發明之植物疾病防治組成物之方法而使用本發明之植物 疾病防治組成物予以進行。 稻作植物:稻熱病菌(Magnaporthe grisea)、胡麻葉枯 病(Cochliobolus miyabeanus)、立枯絲核菌(Rhizoctonia solani)、水稻徒長病菌(Gibberella fujikuroi)、大孢指疫 霉(S cl erophthor a macrospor a);小麥、大麥和燕麥:小麥 白粉病(Erysiphe graminis)、禾本科鎌孢菌(Fusarium . graminearum)、燕麥鐮孢(F_ avenacerum)、黃色鐮刀菌(F_ culmorum)、雪霉鐮孢菌(Microdochium nivale)、小麥葉 鏽病(Puccinia striiformis)、稈鏽病(P. graminis)、葉鏽病 (P. recondite)、大麥柄鏽菌(Ρ· hordei)、Typhula sp·、雪 腐鐮孢(Micronectriella nivalis)、小麥散黑粉菌(Ustilago tritici)、小麥散黑穗病(U. nuda)、小麥網腥黑粉菌 (Tilletia caries)、眼 點 病(Pseudocercosporella herpotrichoides) 大麥雲紋病菌(Rhynchosporium secalis)、葉枯病(Septoria tritici) ' 小麥穎枯病 -37- 201010989 (Leptosphaeria nodorum)、大麥網斑病菌(Pyren〇phora teres Drechsler)、小麥全蝕病菌(Gaeumannomyces graminis)、偃麥草核腔菌(Pyrenophora tritici-repentis); 柑橘屬植物:柑橘黑色蒂腐病(Diaporthe citri)、柑橘瘡 痂病菌(Elsinoe fawcetti)、柑橘綠徽病(Penicillium digitatum)、柑'橘青黴病(Ρ· italicum);蘋果··花萎病 (Monilinia mali)、蘋果黑腐皮殼(Valsa ceratosperma)、蘋 果白粉病(Podosphaera leucotricha)、磚格孢菌蘋果病原型 _ (Alternaria alternata apple pathotype)、蘋果黑星病菌 (Venturia inaequalis)、炭疽病菌(Glomerella cingulata); 梨:梨黑星病(Venturia nashicola)、梨黑星病菌(V_ pirina)、轉格孢菌日本梨病原型(Alternaria alternata Japanese pear pathotype)、梨赤星病菌(Gymnosporangium haraeanum);桃:褐腐病菌(Monilinia fructicola)、桃黑 星病菌(Cladosporium carpophilum)、Phomopsis sp.;葡 萄:黑痘病(Elsinoe ampelina)、葡萄晚腐病菌(Glomerella @ cingulata) 白粉病菌(Uncinula necator) 鏽病 (Phakopsora ampelopsidis)、葡萄黑腐病菌(Guignardia bidwellii)、露菌病(Plasmopara viticola);柿:柿炭疽病 菌(Gloeosporium kaki)、角斑病(Cercospora kaki)、柿圓 斑病(My cosphaerell a nawae) ; Gourds Colletotrichum lagenarium、洋香瓜白粉病(Sphaerotheca fuliginea)、甜 瓜蔓枯病菌(Mycosphaerella melonis)、尖鐮胞菌 (Fusarium oxysporum)、瓜類露菌病菌(Pseudoperonospora -38- 201010989 cubensis)、疫病菌(Phytophthora sp.)、腐霉菌(Pythium sp·);番前:交鏈孢菌(Alternaria solani)、蕃茄葉徵病菌 (Cladosporium fulvum)、致病疫霉(Phytophthora infestans);前子:琉子褐紋病(Phomopsis vexans)、萵宦 白粉病(Erysiphe cichoracearum);芸苔屬植物家族蘿菔黑 斑病菌(Brassica family Alternaria japonica)、藤青白斑病 菌(Cercosporella brassicae)、甘藍根瘤病菌屬寄生 ❹ (Plasmodiophora parasitica)、芸苔霜霉菌(Peronospora parasitica);菌:韭菜鏽病(Puccinia allii);大豆:大豆 紫斑病菌(Ce_rcospora kikuchii)、大豆黑痘病菌(Elsinoe glycines)、Diaporthe phaseolorum var. sojae、亞洲大豆 鏽病(Phakopsora pachyrhizi);敏豆:菜豆炭疽病菌 (Colletotrichum lindemthianum);花生:落花生黑溫病菌 (Cercospora personata)、落花生褐斑病菌(Cercospora arachidicola)、白絹菌(Sclerotium rolfsii);豌豆:婉豆白 • 粉病菌(Erysiphe pisi);馬鈴薯:交鏈孢菌、致病疫霉、 黃萎輪枝菌(Verticillium albo-atrum)、大麗輪枝菌(V. dahliae)、變黑輪枝菌(V. nigrescens);草莓:草莓白粉病 (Sphaerotheca humuli);茶作物:茶網餅病病原菌 (Exobasidium reticulatum)、 茶瘡痂病菌(Elsinoe leucospila)、 子 囊 菌 門(Pestalotiopsis sp.)、 Colletotrichum theae-sinensis ;蘇草:蘇草赤星病菌 (Alternaria longipes)、蔽草白粉病菌(Erysiphe cichoracearum)、C ο 11 e t o t r i chum t ab a cum、薛草露菌病菌 -39- 201010989 (Peronospora tab.acina)、煙草疫病菌(Phytophthora nicotianae);甜菜:褐斑病菌(Cercospora beticola)、莧菜 葉斑病菌(Thanatephorus cucumeris)、種黴菌 (Aphanomyces sochlioides);玫瑰:黑斑病(DiplocarponIt produces a selective anti-pathogenic substance. G PR proteins and the like are known as such anti-pathogenic substances (PRPs, EP_A-0 392 225). The production of such anti-pathogenic substances and genetically modified crops is described in ΕΡ-Α-0 392 225, WO 95/3 3 8 1 8 , ΕΡ-Α-0 353 191 and the like. Examples of such anti-pathogenic substances expressed in genetically modified crops include: ion channel inhibitors such as sodium channel inhibitors or calcium channel inhibitors (KP1, KP4 and KP6 toxins are known, etc., which are Produced); purine synthase; biphenylmethyl synthase; chitinase; polydextrose-36-201010989 enzyme; PR protein; and anti-pathogenic substances produced by microorganisms such as peptide antibiotics, antibiotics with heterocycles A protein factor associated with plant disease resistance (which is referred to as the plant disease resistance gene and is described in WO 03/000906). As a plant disease which can be controlled by the compound of the present invention, for example, a plant disease caused by a filamentous fungus is mentioned. More specific examples include, but are not limited to, the following diseases. The method for controlling a plant disease according to the present invention is usually carried out by using the plant disease controlling composition of the present invention in accordance with the above method for applying the plant disease controlling composition of the present invention. Rice-growing plants: Magnaporthe grisea, Cochliobolus miyabeanus, Rhizoctonia solani, Gibberella fujikuroi, S cl erophthor a macrospor a); wheat, barley and oats: Erysiphe graminis, Fusarium graminearum, F_ avenacerum, F_ culmorum, Fusarium oxysporum Microdochium nivale), Puccinia striiformis, P. graminis, P. recondite, R. hordei, Typhula sp. , Ustilago tritici, Wheat smut (U. nuda), Tilletia caries, Pseudocercosporella herpotrichoides, Rhynchosporium secalis, leaves Blight (Septoria tritici) 'Bright wheat blight -37- 201010989 (Leptosphaeria nodorum), Pyren〇phora teres Drechsler, small Gaeumannomyces graminis, Pyrenophora tritici-repentis; Citrus: Diaporthe citri, Elsinoe fawcetti, Penicillium digitatum , mandarin orange peony (Ρ· italicum); apple · wilting (Monilinia mali), apple black husk (Valsa ceratosperma), apple powdery mildew (Podosphaera leucotricha), brick bacillus apple disease prototype _ ( Alternaria alternata apple pathotype), Venturia inaequalis, Glomerella cingulata; Pear: Venturia nashicola, V_ pirina, Rhizoctonia chinensis pear prototype (Alternaria alternata Japanese pear pathotype), Gymnosporangium haraeanum; peach: Monilinia fructicola, Cladosporium carpophilum, Phomopsis sp.; grape: black pox (Elsinoe ampelina), grape Late rot (Glomerella @ cingulata) Phytophthora (Uncinula necator) rust (Phakopsora) Ampelopsidis), Guignardia bidwellii, Plasmopara viticola; persimmon: Gloeosporium kaki, Cercospora kaki, My cosphaerell a nawae; Gourds Colletotrichum lagenarium, Sphaerotheca fuliginea, Mycosphaerella melonis, Fusarium oxysporum, Phytophthora spp. (Pseudoperonospora -38- 201010989 cubensis), Phytophthora sp. ), Pythium sp.; before: Alternaria solani, Cladosporium fulvum, Phytophthora infestans; anterior: Phomopsis vexans ), Erysiphe cichoracearum; Brassica family Alternaria japonica, Cercosporella brassicae, Plasmodiophora parasitica, Brassica Peronospora parasitica; bacteria: amaranth rust (Puccinia allii); large : Ce_rcospora kikuchii, Elsinoe glycines, Diaporthe phaseolorum var. sojae, Asian soybean rust (Phakopsora pachyrhizi); Sensitive bean: Colletotrichum lindemthianum; Peanut: Arachis chinensis Cercospora personata), Cercospora arachidicola, Sclerotium rolfsii; Pea: Erysiphe pisi; Potato: Alternaria, Phytophthora infestans, Verticillium Verticillium albo-atrum, V. dahliae, V. nigrescens; strawberry: Sphaerotheca humuli; tea crop: Excasidium Reticulatum), Elsinoe leucospila, Pestalotiopsis sp., Colletotrichum theae-sinensis; Su grass: Alternaria longipes, Erysiphe cichoracearum, C ο 11 etotri Chum t ab a cum, Phytophthora infestans -39- 201010989 (Peronospora tab.acina), tobacco Pathogen (Phytophthora nicotianae); beet: leaf spot (Cercospora beticola), amaranth leaf spot fungus (Thanatephorus cucumeris), species of fungus (Aphanomyces sochlioides); Rose: black spot (Diplocarpon
rosae)、玫瑰白粉病(Sphaerotheca pannosa);菊花:野菊 殼針孢(Septoria chrysanthemi-indici)、菊花白鏽病 (Puccinia horiana);洋菌:灰徽菌(Botrytis cinerea)、細 絲葡萄孢(B. byssoidea)、菜灰霉(B. squamosa)、洋菌 頸腐病(Botrytis alii);各種作物:灰徽菌、菌核病菌 (Sclerotinia sclerotiorum);蘿蔔:十字花科黑斑病菌 (Alternaria brassicicola);草地:真菌圓斑病菌 (Sclerotinia homeocarpa)、立枯絲核菌(Rhizoctonia so.lani); 和香蕉:香蕉葉斑病菌(Mycosphaerella fijiensis)、褐緣灰斑病(Mycosphaerella musicola)。 【實施方式】 實例 下面顯示本發明之製造實例、製劑實例和試驗實例。 製造實例1 將0.26 g的碳酸鉋加到0.20 g N-(2-氟-3-羥基苯基) 甲基-苯並噻唑-6-羧醯胺、0.10 g 3-溴-1-丙烯和 5 ml DMF的混合物中,且混合物在室溫攪拌4小時。將水加 到反應混合物中,和過濾收集所產生的固體。固體依序用 -40- 201010989 氫氧化鈉水溶液、水和己烷清洗,而得到0.22 g的N-(2-氟-3-(2 -丙烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱 爲本發明化合物(1))。 本發明化合物(1 )Rosaae), Sphaerotheca pannosa; Chrysanthemum: Septoria chrysanthemi-indici, Puccinia horiana; Botrytis cinerea, Botrytis cinerea Byssoidea), B. squamosa, Botrytis alii; various crops: gray bacterium, sclerotinia sclerotiorum; radish: Alternaria brassicicola; Grassland: Sclerotinia homeocarpa, Rhizoctonia so.lani; and banana: Mycosphaerella fijiensis, Mycosphaerella musicola. [Examples] Examples of the production examples, formulation examples and test examples of the present invention are shown below. Production Example 1 0.26 g of carbonic acid planer was added to 0.20 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.10 g of 3-bromo-1-propene and 5 In a mixture of ml DMF, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with -40-201010989 aqueous sodium hydroxide solution, water and hexane to give 0.22 g of N-(2-fluoro-3-(2-propenyloxy)phenyl)methyl-benzothiazole-6. Carboxylamidine (hereinafter referred to as Compound (1) of the present invention). The compound of the invention (1)
H-NMR (CDC13) 6: 9.11 (1Η, s), 8.48 (1H, s), 8.16 (1H, d, J = 8.5 Hz), 7.88 (1H, d, J = 8.5 Hz), 7.06-7.02 (2H, m), 6.95-6.91 (1H, m), 6.11-6.02 (1H, m), 5.44 (1H, d, J = 17.4 Hz), 5.32 (1H, d, J = 10.4 Hz), 4.74 (2H, d, J =5.1 Hz), 4.61 (2H, d, J = 5.1 Hz). 製造實例2 將0.26 g的碳酸絶加到0_20 g N-(2-氟-3-羥基苯基) ® 甲基-苯並噻唑-6_羧醯胺、0.13 g 5-溴-1-戊烯和5 ml DMF的混合物中,且混合物在室溫攪拌4小時。將水加 到反應混合物中,和過濾收集所產生的固體。固體依序用 氫氧化鈉水溶液、水和己烷清洗,而得到0.23 g的N-(2-氟-3-(4-戊烯氧基)苯基)甲基-苯並噻唑-6_羧醯胺(下文稱 爲本發明化合物(2))。H-NMR (CDC13) 6: 9.11 (1Η, s), 8.48 (1H, s), 8.16 (1H, d, J = 8.5 Hz), 7.88 (1H, d, J = 8.5 Hz), 7.06-7.02 ( (2H, d, J = 17.4 Hz), 5.32 , d, J = 5.1 Hz), 4.61 (2H, d, J = 5.1 Hz). Manufacturing Example 2 Add 0.26 g of carbonic acid to 0_20 g of N-(2-fluoro-3-hydroxyphenyl) ® methyl a mixture of benzothiazole-6-carboxamide, 0.13 g of 5-bromo-1-pentene and 5 ml of DMF, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.23 g of N-(2-fluoro-3-(4-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxyindole. Amine (hereinafter referred to as compound (2) of the present invention).
本發明化合物(2) 〇 FInventive Compound (2) 〇 F
-41 - 201010989 'H-NMR (CDC13) δ: 1.90-1.97 (2H, m), 2.23-2.29 (2H, m), 4.03-4.06 (2H, m), 4.74 (2H, d, J = 5.3 Hz), 5.00-5.10 (2H, m), 5.82-5.89 ( 1H, m), 6.62 (1H, s), 6.90-6.95 (1 H, m), 6.98-7.06 (2H, m), 7.87-7.89 (1H, m), 8.16 (1H, d, J =8.5 Hz), 8.48 (1H, s), 9.11 (1H, s). 製造實例3 將0.26 g的碳酸鉋加到0.20 g N-(2-氟-3-羥基苯基) ❹ 甲基-苯並噻唑-6 -羧醯胺、0.14 g 6 -溴-1-己烯和 5 ml DMF的混合物中,且混合物在室溫攪拌4小時。將水加 到反應混合物中,和過濾收集所產生的固體。固體依序用 氫氧化鈉水溶液、水和己烷清洗,而得到0.22 g的Ν·(2-氟- 3-(5-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱 爲本發明化合物(3))。 本發明化合物(3)-41 - 201010989 'H-NMR (CDC13) δ: 1.90-1.97 (2H, m), 2.23-2.29 (2H, m), 4.03-4.06 (2H, m), 4.74 (2H, d, J = 5.3 Hz ), 5.00-5.10 (2H, m), 5.82-5.89 (1H, m), 6.62 (1H, s), 6.90-6.95 (1 H, m), 6.98-7.06 (2H, m), 7.87-7.89 ( 1H, m), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, s), 9.11 (1H, s). Production Example 3 0.26 g of carbonic acid planer was added to 0.20 g of N-(2-fluoro A mixture of -3-hydroxyphenyl)indolemethyl-benzothiazole-6-carboxamide, 0.14 g of 6-bromo-1-hexene and 5 ml of DMF, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.22 g of bis(2-fluoro-3-(5-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxyindole. Amine (hereinafter referred to as compound (3) of the present invention). Inventive compound (3)
*H-NMR (CDCI3) δ: 1.56-1.63 (2Η, m), 1.81-1.88 (2H, m), 2.11-2.17 (2H, m), 4.04 (2H, t, J = 6.4 Hz), 4.74 (2H, d, J = 5.8 Hz), 4.96-5.07 (2H, m), 5.78-5.88 ( 1 H, m), 6.59 (1H, s), 6.92 (1H, td, J = 8.0, 1.9 Hz), 6.98-7.06 (2H, m), 7.88 (1H,dd, J = 8.5,1.7 Hz), 8.16 (1H,d,J = 8.7 Hz), 8.48 (1H, d, J = 1.4 Hz), 9.11 (1H, s). -42 - 201010989 製造實例4*H-NMR (CDCI3) δ: 1.56-1.63 (2Η, m), 1.81-1.88 (2H, m), 2.11-2.17 (2H, m), 4.04 (2H, t, J = 6.4 Hz), 4.74 ( 2H, d, J = 5.8 Hz), 4.96-5.07 (2H, m), 5.78-5.88 ( 1 H, m), 6.59 (1H, s), 6.92 (1H, td, J = 8.0, 1.9 Hz), 6.98-7.06 (2H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.7 Hz), 8.48 (1H, d, J = 1.4 Hz), 9.11 (1H , s). -42 - 201010989 Manufacturing Example 4
將〇·26 g的碳酸絶加到0.20 g N-(2-氟-3-羥基苯基) 甲基-苯並噻唑-6-羧醯胺、0.15 g 7-溴-1-庚烯和5 ml DMF的混合物中,且混合物在室溫攪拌4小時。將水加 到反應混合物中,和過濾收集所產生的固體。固體依序用 氫氧化鈉水溶液、水和己烷清洗,而得到0.24 g的^^(2-氟-3-(6-庚烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱 爲本發明化合物(4))。 本發明化合物(4)〇·26 g of carbonic acid was absolutely added to 0.20 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.15 g of 7-bromo-1-heptene and 5 In a mixture of ml DMF, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.24 g of (2-fluoro-3-(6-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxyindole. Amine (hereinafter referred to as compound (4) of the present invention). The compound of the invention (4)
F ^^L/OCH2CH2CH2CH2CH2CH=CH2F ^^L/OCH2CH2CH2CH2CH2CH=CH2
U JH-NMR (CDC13) δ: 1.47- 1.50 (4Η, m), 1.80- 1.87 (2Η, m), 2.07-2.12 (2H, m), 4.03 (2H, t, J = 6.5 Hz), 4.74 (2H, 參 d, J = 5.8 Hz), 4.93 -5.04 (2H, m), 5.77-5.87 ( 1 H, m), 6.60 (1H, s), 6.90-6.94 (1 H, m), 6.98-7.06 (2H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, d, J = 1.4 Hz), 9.11 (1H, s). 製造實例5U JH-NMR (CDC13) δ: 1.47- 1.50 (4Η, m), 1.80- 1.87 (2Η, m), 2.07-2.12 (2H, m), 4.03 (2H, t, J = 6.5 Hz), 4.74 ( 2H, Ref, J = 5.8 Hz), 4.93 -5.04 (2H, m), 5.77-5.87 ( 1 H, m), 6.60 (1H, s), 6.90-6.94 (1 H, m), 6.98-7.06 (2H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, d, J = 1.4 Hz), 9.11 (1H, s) Manufacturing example 5
將0.23 g碳酸鉀加到0.30 g N-(2-氟-3-羥基苯基)甲 基-苯並噻唑-6-羧醯胺、0.16 g 1-溴-2-戊烯和5 ml DMF 的混合物中,且混合物在室溫攪拌6小時。將水加到反應 -43- 201010989 混合物中,且混合物用乙酸乙酯萃取。有機層用飽和食鹽 水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留 物進行矽膠層析術,而得到0.24 g的N-(2-氟-3-(2-戊烯 氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合 物(5)) 〇 本發明化合物(5 )0.23 g of potassium carbonate was added to 0.30 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.16 g of 1-bromo-2-pentene and 5 ml of DMF. The mixture was stirred and the mixture was stirred at room temperature for 6 hours. Water was added to the mixture -43-201010989, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, then dried over magnesium sulfate and evaporated. The obtained residue was subjected to silica gel chromatography to obtain 0.24 g of N-(2-fluoro-3-(2-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is a compound of the invention (5)) 〇 a compound of the invention (5)
'H-NMR (CDC13) δ: 1.02 (3.0H,td,J = 7.5,1.4 Hz), 2.08-2.19 (2.OH, m), 4.54 (1.0H, d, J = 5.8 Hz), 4.66 (1.0H, d, J = 5.3 Hz), 4.74 (2.OH, d, J = 5.8 Hz), 5.62-5.75 (1.5H, m), 5.87-5.94 (0.5H, m), 6.62 (1.0H, s), 6.91-7.06 (3.OH, m), 7.87 (1.0H, dd, J = 8.5, 1.7 Hz), 8.15 (1.0H, d, J = 8.5 Hz), 8.47 (1.0H, d, J = 1.4 Hz), 9.11 (1 .OH, s). 製造實例6 將0.28 g碳酸铯加到0.20 g N-(3-羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.11 g 3-溴-1-丙烯和3 ml DMF的混合 物中,且混合物在室溫攪拌7小時。將水和氫氧化鈉水溶 液加到反應混合物中,且混合物用乙酸乙酯萃取。有機層 用飽和食鹽水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。 所得之殘留物進行矽膠層析術,而得到0.18 g的N-(3- 201010989 (2-丙烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發 明化合物(6))。 本發明化合物(6) Ο'H-NMR (CDC13) δ: 1.02 (3.0H, td, J = 7.5, 1.4 Hz), 2.08-2.19 (2.OH, m), 4.54 (1.0H, d, J = 5.8 Hz), 4.66 ( 1.0H, d, J = 5.3 Hz), 4.74 (2.OH, d, J = 5.8 Hz), 5.62-5.75 (1.5H, m), 5.87-5.94 (0.5H, m), 6.62 (1.0H, s), 6.91-7.06 (3.OH, m), 7.87 (1.0H, dd, J = 8.5, 1.7 Hz), 8.15 (1.0H, d, J = 8.5 Hz), 8.47 (1.0H, d, J = 1.4 Hz), 9.11 (1.OH, s). Production Example 6 0.28 g of cesium carbonate was added to 0.20 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.11 g. A mixture of 3-bromo-1-propene and 3 ml of DMF was added, and the mixture was stirred at room temperature for 7 hours. Water and a sodium hydroxide aqueous solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The obtained residue was subjected to silica gel chromatography to obtain 0.18 g of N-(3-201010989 (2-propenyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as the compound of the present invention). (6)). Inventive compound (6) Ο
^-NMR (CDC13) δ: 4.51-4.54 (2Η, m), 4.65 (2H, d, J o =5.6 Hz), 5.26-5.30 ( 1 H, m), 5.38-5.43 ( 1 H, m), 5.99-6.09 (1H, m), 6.62 (1H, s), 6.86 (1H, dd, J = 8.2, 1.9 Hz), 6.94-6.96 (2H, m), 7.27 (1H, t, J = 7.8 Hz), 7.89 (1H, dd, J = 8.6, 1.6 Hz), 8.15 (1H, d, J = 8.5 Hz), 8.49 (1H, d, J = 1.7 Hz), 9.10 (1H, s). 製造實例7 將0.45 g碳酸铯加到0.30 g N-(3-羥基苯基)甲基-苯 β 並噻唑-6-羧醯胺、0.19 g 5-溴-1-戊烯和5 ml DMF的混合 物中,且混合物在室溫攪拌6小時。將水和氫氧化鈉水溶 液加到反應混合物中,且混合物用乙酸乙酯萃取。有機層 用飽和食鹽水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。 所得之殘留物被濃縮,接著所產生之固體用己烷清洗,而 得到0.11 g的N-(3-(4-戊烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物(7))。 本發明化合物(7) -45- 201010989^-NMR (CDC13) δ: 4.51-4.54 (2Η, m), 4.65 (2H, d, J o =5.6 Hz), 5.26-5.30 ( 1 H, m), 5.38-5.43 ( 1 H, m), 5.99-6.09 (1H, m), 6.62 (1H, s), 6.86 (1H, dd, J = 8.2, 1.9 Hz), 6.94-6.96 (2H, m), 7.27 (1H, t, J = 7.8 Hz) , 7.89 (1H, dd, J = 8.6, 1.6 Hz), 8.15 (1H, d, J = 8.5 Hz), 8.49 (1H, d, J = 1.7 Hz), 9.10 (1H, s). Manufacturing Example 7 0.45 g of cesium carbonate was added to a mixture of 0.30 g of N-(3-hydroxyphenyl)methyl-benzene β-thiazole-6-carboxamide, 0.19 g of 5-bromo-1-pentene and 5 ml of DMF, and The mixture was stirred at room temperature for 6 hours. Water and a sodium hydroxide aqueous solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue obtained was concentrated, and the resulting solid was washed with hexane to give 0.11 g of N-(3-(4-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide. (hereinafter referred to as the compound (7) of the present invention). The compound of the invention (7) -45- 201010989
.◦ch2ch2ch2ch=ch2 !H-NMR (CDC13) δ: 1.85- 1.92 (2H, m), 2.21-2.26 (2H, in), 3.97 (2H, t, J = 6.4 Hz), 4.66 (2H, d, J = 5.6 Hz), 4.98-5.01 (1H, m), 5.03-5.09 ( 1 H, m), 5.80- 5.90 ( 1 H, m), 6.46 (1H, s), 6.85 (1H, dd, J = 8.0, 2.2 Hz), 6.92-6.96 (2H, m), 7.26-7.30 ( 1 H, m), 7.89 (1H, dd, J = 8.6, 1.8 Hz),❿ 8.17 (1H, d, J = 8.5 Hz), 8.51 (1H, d, J = 1.4 Hz), 9.12 (1H, s). 製造實例8 將0.45 g碳酸絶加到0.30 g N-(3-羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.21 g 6-溴-1-己烯和5 ml DMF的混合 物中,且混合物在室溫攪拌6小時。將水和氫氧化鈉水溶 液加到反應混合物中,且混合物用乙酸乙酯萃取。有機層 參 用飽和食鹽水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。 所得之殘留物被濃縮,接著所產生之固體用己烷清洗,而 得到0.14 g的N-(3-(5-己烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物(8))。 本發明化合物(8 ).◦ch2ch2ch2ch=ch2 !H-NMR (CDC13) δ: 1.85- 1.92 (2H, m), 2.21-2.26 (2H, in), 3.97 (2H, t, J = 6.4 Hz), 4.66 (2H, d, J = 5.6 Hz), 4.98-5.01 (1H, m), 5.03-5.09 ( 1 H, m), 5.80- 5.90 ( 1 H, m), 6.46 (1H, s), 6.85 (1H, dd, J = 8.0, 2.2 Hz), 6.92-6.96 (2H, m), 7.26-7.30 ( 1 H, m), 7.89 (1H, dd, J = 8.6, 1.8 Hz), ❿ 8.17 (1H, d, J = 8.5 Hz) ), 8.51 (1H, d, J = 1.4 Hz), 9.12 (1H, s). Production Example 8 0.45 g of carbonic acid was absolutely added to 0.30 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6 a mixture of carboxyguanamine, 0.21 g of 6-bromo-1-hexene and 5 ml of DMF, and the mixture was stirred at room temperature for 6 hours. Water and a sodium hydroxide aqueous solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue obtained was concentrated, and the resulting solid was washed with hexane to give 0.14 g of N-(3-(5-hexenyloxy)phenyl)methyl-benzothiazole-6-carboxamide. (hereinafter referred to as the compound (8) of the present invention). Inventive compound (8)
-46- 201010989 W-NMR (CDC13) δ: 1.5 3 - 1.60 (2H,m), 1.76- 1.83 (2H, m), 2.09-2.15 (2H, m), 3.97 (2H, t, J - 6.4 Hz), 4.66 (2H, d, J = 5.8 Hz), 4.95-4.98 (1 H, m), 5.00-5.06 (2H, m), 5.77-5.87 (1 H, m), 6.46 (1H, s), 6.84 (1H, dd, J = 8.1, 2.1 Hz), 6.92-6.96 (2H, m), 7.26-7.30 (1 H, m), 7.88 (1H, dd, J = 8.6, 1.8 Hz), 8.17 (1H, d, J = 8.7 Hz), 8.51 (1H, d, J =1.4 Hz), 9.12 (1H, s). 參 製造實例9 將0.26 g碳酸鉋加到0.20 g N-(3 -羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.16 g 7-溴-1-庚烯和5 ml DMF的混合 物中,且混合物在室溫攪拌4小時。將水加到反應混合物 中,和過濾收集所產生的固體。固體依序用氫氧化鈉水瘠 液、水和己烷清洗,而得到0.12 g的N-(3-(6-庚烯氧基) 苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 β (9))。 本發明化合物(9 ) Ο-46- 201010989 W-NMR (CDC13) δ: 1.5 3 - 1.60 (2H, m), 1.76- 1.83 (2H, m), 2.09-2.15 (2H, m), 3.97 (2H, t, J - 6.4 Hz ), 4.66 (2H, d, J = 5.8 Hz), 4.95-4.98 (1 H, m), 5.00-5.06 (2H, m), 5.77-5.87 (1 H, m), 6.46 (1H, s), 6.84 (1H, dd, J = 8.1, 2.1 Hz), 6.92-6.96 (2H, m), 7.26-7.30 (1 H, m), 7.88 (1H, dd, J = 8.6, 1.8 Hz), 8.17 (1H , d, J = 8.7 Hz), 8.51 (1H, d, J = 1.4 Hz), 9.12 (1H, s). Reference Example 9 0.26 g of carbonic acid planer was added to 0.20 g of N-(3-hydroxyphenyl) A mixture of methyl-benzothiazole-6-carboxyguanamine, 0.16 g of 7-bromo-1-heptene and 5 ml of DMF was added, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with sodium hydroxide aqueous hydrazine, water and hexane to give 0.12 g of N-(3-(6-heptenyloxy)phenyl)methyl-benzothiazole-6-carboxamide ( Hereinafter referred to as the compound β (9)) of the present invention. The compound of the invention (9 ) Ο
'H-NMR (CDC13) δ: 9.11 (1Η, s), 8.50 (1H, d, J = 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 7.27 (1H, t, J = 7.9 Hz), 6.95-6.91 (2H, m), 6.84 (1H, dd, J = 8.3, 2.4 Hz), 6.50 (1H, s), 5.86-5.76 ( 1H, m), 5.00 -47- 201010989 (1H, dq, J = 17.1, 1.7 Hz), 4.94 (1H, dd, J = 10.2, 2.0 Hz), 4.66 (2H, d, J = 5.6 Hz), 3.95 (2H, t, J = 6.5 Hz), 2.08 (2H, d, J = 6.8 Hz), 1.82- 1.75 (2H, m), 1.52-1.42 (4H, m). 製造實例10 將0.28 g碳酸鉋加到0.20 g N-(3-羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.12 g 1-溴-2-丁烯和5 ml DMF的混合 物中,且混合物在室溫攪拌4小時。將水加到反應混合物 參 中,和過濾收集所產生的固體。固體依序用氫氧化鈉水溶 液、水和己烷清洗,而得到0.23 g的N-(3-(2-丁烯氧基) 苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (10))。 本發明化合物(10)'H-NMR (CDC13) δ: 9.11 (1Η, s), 8.50 (1H, d, J = 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 7.27 (1H, t, J = 7.9 Hz), 6.95-6.91 (2H, m), 6.84 (1H, dd, J = 8.3, 2.4 Hz), 6.50 (1H, s), 5.86-5.76 ( 1H, m), 5.00 -47- 201010989 (1H, dq, J = 17.1, 1.7 Hz), 4.94 (1H, dd, J = 10.2, 2.0 Hz), 4.66 (2H, d, J = 5.6 Hz), 3.95 (2H, t, J = 6.5 Hz), 2.08 (2H, d, J = 6.8 Hz), 1.82- 1.75 (2H, m), 1.52-1.42 (4H, m). Manufacturing Example 10 0.28 g of carbonic acid planing To a mixture of 0.20 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.12 g of 1-bromo-2-butene and 5 ml of DMF, and the mixture was stirred at room temperature 4 hour. Water was added to the reaction mixture and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.23 g of N-(3-(2-butoxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as It is the compound (10)) of the present invention. Inventive Compound (10)
^-NMR (CDC13) 6: 9.12 (1Η, s), 8.50 (1H, s), 8.16 (1H, d, J = 8.5 Hz), 7.89 (1H, d, J = 8.5 Hz), 7.27 (1H, t, J = 7.8 Hz), 6.95 (2H, d, J = 12.3 Hz), 6.86 (1H, dd, J = 7.8, 2.3 Hz), 6.54 (1H, s), 5.90-5.82 ( 1 H, m), 5.75-5.69 (1H, m), 4.66 (2H, d, J = 5.6 Hz), 4.46 (2H, d, J = 5.8 Hz), 1.74 (3H, d, J = 6.0 Hz). 製造實例11 48 - 201010989 將0.28 g碳酸鉋加到0.20 g N-(3-羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.14 g 1-溴-2-戊烯和5 ml DMF的混合 物中,且混合物在室溫攪拌4小時。將水加到反應混合物 中,和過濾收集所產生的固體。固體依序用氫氧化鈉水溶 液、水和己烷清洗,而得到0.18 g的N-(3-(2-戊烯氧基) 苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (11))。 參^-NMR (CDC13) 6: 9.12 (1Η, s), 8.50 (1H, s), 8.16 (1H, d, J = 8.5 Hz), 7.89 (1H, d, J = 8.5 Hz), 7.27 (1H, t, J = 7.8 Hz), 6.95 (2H, d, J = 12.3 Hz), 6.86 (1H, dd, J = 7.8, 2.3 Hz), 6.54 (1H, s), 5.90-5.82 ( 1 H, m) , 5.75-5.69 (1H, m), 4.66 (2H, d, J = 5.6 Hz), 4.46 (2H, d, J = 5.8 Hz), 1.74 (3H, d, J = 6.0 Hz). Manufacturing Example 11 48 - 201010989 Add 0.28 g of carbonic acid planing to a mixture of 0.20 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.14 g of 1-bromo-2-pentene and 5 ml of DMF And the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to obtain 0.18 g of N-(3-(2-pentenyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is the compound (11)) of the present invention. Reference
本發明化合物(1 1) 〇The compound of the present invention (1 1) 〇
OCH2CH=CHCH2CH3 !H-NMR (CDC13) 6: 9.12 (1H? d, J = 0.7 Hz), 8.50 (1H, s), 8.17 (1H, d, J = 8.5 Hz), 7.89 (1H, d, J = 8.5 Hz), 7.30-7.24 ( 1 H, m), 6.96-6.94 (2H, m), 6.86 (1H, dd, J -8.0, 2.4 Hz), 6.49 ( 1 H,s),5.9 2 - 5 · 6 0 ( 2 H,m ),4 · 6 7 - 4.4 8 (4H, m), 2.18-2.06 (2H, m), 1.01 (3H, t, J = 7.5 Hz). 製造實例12OCH2CH=CHCH2CH3 !H-NMR (CDC13) 6: 9.12 (1H? d, J = 0.7 Hz), 8.50 (1H, s), 8.17 (1H, d, J = 8.5 Hz), 7.89 (1H, d, J = 8.5 Hz), 7.30-7.24 ( 1 H, m), 6.96-6.94 (2H, m), 6.86 (1H, dd, J -8.0, 2.4 Hz), 6.49 ( 1 H, s), 5.9 2 - 5 · 6 0 ( 2 H,m ), 4 · 6 7 - 4.4 8 (4H, m), 2.18-2.06 (2H, m), 1.01 (3H, t, J = 7.5 Hz). Manufacturing Example 12
將0.28 g碳酸鉋加到0.20 g N-(2-氟-3-羥基苯基)甲 基-苯並噻唑-6-羧醯胺、0.10 g 3-溴-1-丙炔和5 ml DMF 的混合物中,且混合物在室溫攪拌4小時。將水加到反應 混合物中,和過濾收集所產生的固體。固體依序用氫氧化 鈉水溶液、水和己烷清洗,而得到0.17 g的N-(2-氟-3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發 -49- 201010989 明化合物(12))。 本發明化合物(12)0.28 g of carbonic acid was added to 0.20 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.10 g of 3-bromo-1-propyne and 5 ml of DMF. The mixture was stirred and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.17 g of N-(2-fluoro-3-(2-propynyloxy)phenyl)methyl-benzothiazole-6-carboxyindole. Amine (hereinafter referred to as the present invention - 49 - 201010989 Compound (12)). Inventive Compound (12)
F ^X.och2c=chF ^X.och2c=ch
U 1H-NMR (CDCI3) δ: 9.12 (1Η, s), 8.48 (1H, s), 8.16 (1H, d, J = 8.7 Hz), 7.88 (1H, d, J = 8.5 Hz), 7.08-7.07 φ (3H, m), 6.65 (1H, s), 4.78 (2H, d, J = 2.4 Hz), 4.74 (2H, d, J = 5.8 Hz), 2.55 (1H, t, J = 2.4 Hz). 製造實例13 將0.11 g 5-氯-1-戊炔加到0.25 g N-(2-氟-3-羥基苯 基)甲基-苯並噻唑-6-羧醯胺、約10 mg碘化鈉、36 mg 的55%氫化鈉(於油中)和4 ml DMF的混合物中,且混合 物在80°C攪拌2小時,接著在100°C攪拌2小時。讓反應 參 混合物冷卻至約室溫。將水和氫氧化鈉水溶液加到反應混 合物中,且混合物用乙酸乙酯萃取。有機層用飽和食鹽水 清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留物 進行矽膠層析術,而得到0.22 g的N-(2-氟-3-(4-戊炔氧 基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (13))。 本發明化合物(13) -50- 201010989U 1H-NMR (CDCI3) δ: 9.12 (1Η, s), 8.48 (1H, s), 8.16 (1H, d, J = 8.7 Hz), 7.88 (1H, d, J = 8.5 Hz), 7.08-7.07 φ (3H, m), 6.65 (1H, s), 4.78 (2H, d, J = 2.4 Hz), 4.74 (2H, d, J = 5.8 Hz), 2.55 (1H, t, J = 2.4 Hz). Production Example 13 0.11 g of 5-chloro-1-pentyne was added to 0.25 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, about 10 mg of sodium iodide In a mixture of 36 mg of 55% sodium hydride (in oil) and 4 ml of DMF, and the mixture was stirred at 80 ° C for 2 hours, followed by stirring at 100 ° C for 2 hours. The reaction mixture was allowed to cool to about room temperature. Water and aqueous sodium hydroxide solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue obtained was subjected to silica gel chromatography to obtain 0.22 g of N-(2-fluoro-3-(4-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is the compound (13)) of the present invention. The compound of the invention (13) -50- 201010989
och2ch2ch2c=ch JH-NMR (CDC13) δ: 1.98 (1H, t, J = 2.7 Hz), 2.01-2.08 (2H, m), 2.45 (2H, td, J = 6.9, 2.6 Hz), 4.15 (2H, t, J = 6.1 Hz), 4.74 (2H, d, J = 5.4 Hz), 6.58 (1H, s), 6.93-7.07 (3H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, ❹ J - 8.5 Hz), 8.48 (1H, d, J = 1.5 Hz), 9.11 (1H, s). 製造實例1 4 將0.13 g 6-氯-1-己炔加到0.25 g N-(2-氟-3-羥基苯 基)甲基-苯並噻唑-6-羧醯胺、約10 mg碘化鈉、36 mg 的55%氫化鈉(於油中)和4 ml DMF的混合物中,且混合 物在攪拌2小時,接著在100°C攪拌2小時。讓反應 混合物冷卻至約室溫。將水和氫氧化鈉水溶液加到反應混 ® 合物中,且混合物用乙酸乙酯萃取。有機層用飽和食鹽水 清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留物 進行矽膠層析術,而得到〇·23 g的N-(2-氟-3-(5-己炔氧 基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (14))。Och2ch2ch2c=ch JH-NMR (CDC13) δ: 1.98 (1H, t, J = 2.7 Hz), 2.01-2.08 (2H, m), 2.45 (2H, td, J = 6.9, 2.6 Hz), 4.15 (2H, t, J = 6.1 Hz), 4.74 (2H, d, J = 5.4 Hz), 6.58 (1H, s), 6.93-7.07 (3H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, ❹ J - 8.5 Hz), 8.48 (1H, d, J = 1.5 Hz), 9.11 (1H, s). Manufacturing example 1 4 Add 0.13 g of 6-chloro-1-hexyne to 0.25 g N-(2-Fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, about 10 mg sodium iodide, 36 mg 55% sodium hydride (in oil) and 4 ml DMF The mixture was stirred for 2 hours and then stirred at 100 ° C for 2 hours. The reaction mixture was allowed to cool to about room temperature. Water and aqueous sodium hydroxide solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue obtained was subjected to silica gel chromatography to obtain 23 g of N-(2-fluoro-3-(5-hexynyloxy)phenyl)methyl-benzothiazole-6-carboxamide ( Hereinafter referred to as the compound (14) of the present invention.
本發明化合物(14) Ο FInventive Compound (14) Ο F
-51 - 201010989 *H-NMR (CDC13) δ: 1.71.1.78 (2H, m), 1.92-1.99 (3H, m),2.29 (2H,td,J = 7.〇,2.6 Hz), 4.06 (2H,t, J = 6.2 Hz), 4.73 (2H, d, J = 5.6 Hz), 6.63 (1H, s), 6.90-6.94 (1H, m),6.98-7.06 (2H, m),7 88 ( 1 H,dd, J = 8.5,1.5 Hz), 8.15 (1H,d,J = 8.5 Hz),8·47 (1H,d,J = 1.0 Hz), 9.11 (1H, s). 製造實例15-51 - 201010989 *H-NMR (CDC13) δ: 1.71.1.78 (2H, m), 1.92-1.99 (3H, m), 2.29 (2H, td, J = 7.〇, 2.6 Hz), 4.06 (2H ,t, J = 6.2 Hz), 4.73 (2H, d, J = 5.6 Hz), 6.63 (1H, s), 6.90-6.94 (1H, m), 6.98-7.06 (2H, m), 7 88 ( 1 H, dd, J = 8.5, 1.5 Hz), 8.15 (1H, d, J = 8.5 Hz), 8.47 (1H, d, J = 1.0 Hz), 9.11 (1H, s). Manufacturing Example 15
將0.23 g碳酸鉀加到〇 25 g n-(2-氟-3-羥基苯基)甲 基-苯並噻唑-6-羧醯胺、0l6 g丨_溴-2-戊炔和4 ml DMF 的混合物中,且混合物在室溫攪拌6小時。將水加到反應 混合物中’且混合物用乙酸乙酯萃取。有機層用飽和食鹽 水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留 物進行矽膠層析術,而得到0.23 g的Ν-(2-氟-3-(2-戊炔 氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合 物(15)) 〇 本發明化合物(15)Add 0.23 g of potassium carbonate to 〇25 g n-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 016 g 丨bromo-2-pentyne and 4 ml DMF The mixture was stirred and the mixture was stirred at room temperature for 6 hours. Water was added to the reaction mixture' and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, then dried over magnesium sulfate and evaporated. The residue obtained was subjected to silica gel chromatography to obtain 0.23 g of Ν-(2-fluoro-3-(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxyguanamine (hereinafter referred to as Is a compound of the invention (15)) 〇 a compound of the invention (15)
Ο FΟ F
!H-NMR (CDCI3) δ: 1.12 (3Η, t, J = 7.4 Hz), 2.19-2.26 (2H, m), 4.74-4.75 (4H, m), 6.59 (1H, s), 7.06-7.07 (3H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, d, J = 1.7 Hz), 9.11 (1H, s). 201010989 製造實例1 6 將0.28 g碳酸鉋加到0.20 g N-(3-羥基苯基甲基)-苯 並噻唑-6-羧醯胺、0.11 g 3-溴-卜丙快和5 ml DMF的混合 物中,且混合物在室溫攪拌4小時。將水和氫氧化鈉水溶 液加到反應混合物中,且混合物用乙酸乙酯萃取。有機層 用飽和食鹽水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。 # 所得之殘留物進行矽膠層析術,而得到0.17 g的N-(3-(2-丙炔氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明 化合物(16))。 本發明化合物(16) Ο!H-NMR (CDCI3) δ: 1.12 (3Η, t, J = 7.4 Hz), 2.19-2.26 (2H, m), 4.74-4.75 (4H, m), 6.59 (1H, s), 7.06-7.07 ( 3H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, d, J = 1.7 Hz), 9.11 (1H, s). 201010989 Manufacturing Example 1 6 0.28 g of carbonic acid planer was added to 0.20 g of N-(3-hydroxyphenylmethyl)-benzothiazole-6-carboxamide, 0.11 g of 3-bromo-abpropan and 5 ml of DMF. The mixture was stirred and the mixture was stirred at room temperature for 4 hours. Water and a sodium hydroxide aqueous solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. # The residue obtained was subjected to silica gel chromatography to obtain 0.17 g of N-(3-(2-propynyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as the present invention). Compound (16)). Inventive compound (16) Ο
j-NMR (CDC13) δ: 9.12 (1H,s), 8.51 (1H, d,J = 1.7 參 Hz), 8.17 (1H, d, J = 8.5 Hz), 7.89 (1H, dd, J = 8.5, 1.7 Hz), 7.31 (1H, t, J = 8.0 Hz), 7.03-7.00 (2H, m), 6.95-6.92 (1H, m), 6.50 (1H, s), 4.70 (2H, d, J = 2.4 Hz), 4.68 (2H, d, J = 5.6 Hz), 2.51 (1H, t, J = 2.4 Hz). 製造實例17 將0.14 g 5-氯-1-戊炔加到0.30 g N-(3-羥基苯基)甲 基-苯並噻唑-6-羧醯胺、約10 mg碘化鈉、5 1 mg的55% 氫化鈉(於油中)和5 ml DMF的混合物中,且混合物在80 -53 - 201010989 。(:攪拌2小時,接著在1 00°C攪拌2小時。讓反應混合物 冷卻至約室溫。將水和氫氧化鈉水溶液加到反應混合物 中,且混合物用乙酸乙酯萃取。有機層用飽和食鹽水清 洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留物進 行矽膠層析術,而得到0.20 g的N-(3-(4-戊炔氧基)苯基) 甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物(17))。 本發明化合物(17) Ο <ΝϊΧ η^〇γ •H-NMR (CDC13) δ: 1.95-2.03 (3H, m), 2.41 (2H, td, J = 7.0, 2.7 Hz), 4.08 (2H, t, J = 6.0 Hz), 4.67 (2H, d, J = 5.6 Hz), 6.45 (1H, s), 6.86 (1H, dd, J = 8.2, 2.4 Hz), 6.93 -6.97 (2H, m), 7.26-7.30 (1 H, m), 7.89 (1H, dd, J = 8.5, 1.7 Hz), 8.17 (1H, d, J = 8.5 Hz), 8.51 (1H, d, J = 1.7 Hz), 9.12 ( 1 H, s). 〇 製造實例18 將0.16 g 6 -氯-1-己炔加到0.30 g N-(3 -羥基苯基)甲 基-苯並唾哩-6-竣酿胺、約10 mg蛛化鈉、51 mg的55% 氫化鈉(於油中)和5 ml DMF的混合物中,且混合物在80 °C攪拌2小時’接著在100°C攪拌2小時。讓反應混合物 冷卻至約室溫。將水和氫氧化鈉水溶液加到反應混合物 中’且混合物用乙酸乙酯萃取。有機層用飽和食鹽水清 -54- 201010989 ) 洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留物進 行矽膠層析術,而得到0.28 g的N-(3-(5-己炔氧基)苯基 甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物(18))。 本發明化合物(1 8)j-NMR (CDC13) δ: 9.12 (1H, s), 8.51 (1H, d, J = 1.7 Hz), 8.17 (1H, d, J = 8.5 Hz), 7.89 (1H, dd, J = 8.5, 1.7 Hz), 7.31 (1H, t, J = 8.0 Hz), 7.03-7.00 (2H, m), 6.95-6.92 (1H, m), 6.50 (1H, s), 4.70 (2H, d, J = 2.4 Hz), 4.68 (2H, d, J = 5.6 Hz), 2.51 (1H, t, J = 2.4 Hz). Manufacturing Example 17 Add 0.14 g of 5-chloro-1-pentyne to 0.30 g of N-(3- a mixture of hydroxyphenyl)methyl-benzothiazole-6-carboxamide, about 10 mg sodium iodide, 5 1 mg of 55% sodium hydride (in oil) and 5 ml DMF, and the mixture is at 80 - 53 - 201010989. (: stirring for 2 hours, followed by stirring at 100 ° C for 2 hours. The reaction mixture was allowed to cool to about room temperature. Water and aqueous sodium hydroxide solution were added to the reaction mixture, and the mixture was extracted with ethyl acetate. It was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography to give 0.20 g of N-(3-(4-pentynyloxy)phenyl)methyl- Benzothiazole-6-carboxyguanamine (hereinafter referred to as the compound (17) of the present invention). The present compound (17) Ο <ΝϊΧ η^〇γ • H-NMR (CDC13) δ: 1.95-2.03 (3H, m), 2.41 (2H, td, J = 7.0, 2.7 Hz), 4.08 (2H, t, J = 6.0 Hz), 4.67 (2H, d, J = 5.6 Hz), 6.45 (1H, s), 6.86 ( 1H, dd, J = 8.2, 2.4 Hz), 6.93 -6.97 (2H, m), 7.26-7.30 (1 H, m), 7.89 (1H, dd, J = 8.5, 1.7 Hz), 8.17 (1H, d , J = 8.5 Hz), 8.51 (1H, d, J = 1.7 Hz), 9.12 ( 1 H, s). 〇Production Example 18 Add 0.16 g of 6-chloro-1-hexyne to 0.30 g of N-(3 a mixture of -hydroxyphenyl)methyl-benzopyrazine-6-anthraquinone, about 10 mg of sodium arachidate, 51 mg of 55% sodium hydride (in oil) and 5 ml of DMF, and The mixture was stirred at 80 ° C for 2 hours' and then at 100 ° C for 2 hours. The reaction mixture was allowed to cool to about room temperature. Water and aqueous sodium hydroxide were added to the mixture, and the mixture was extracted with ethyl acetate. The layer was washed with brine brine - 54 - 201010989) then dried over magnesium sulfate and evaporated. The obtained residue was subjected to silica gel chromatography to obtain 0.28 g of N-(3-(5-hexynyloxy)phenylmethyl-benzothiazole-6-carboxamide (hereinafter referred to as the compound of the present invention ( 18)). Compounds of the invention (1 8)
OCH2CH2CH2CH2CeCH O 'H-NMR (CDC13) δ: 1.68- 1.76 (2H, m),1.8 8- 1.95 (2H, m), 1.96 (1H, t, J = 2.7 Hz), 2.27 (2H, td, J = 7.0, 2.5 Hz), 3.99 (2H, t, J = 6.3 Hz), 4.66 (2H, d, J = 5.6 Hz), 6.46 (1H, s), 6.84 (1H, dd, J = 8.1, 2.3 Hz), 6.92-6.96 (2H, m), 7.26-7.30 ( 1 H, m), 7.89 (1H, dd, J = 8.7, 1.7 Hz), 8.17 (1H, d, J = 8.7 Hz), 8.51 (1H, d, J = 1.7 Hz), 9.12 (1H, s). ® 製造實例19 將0.28 g碳酸鉋加到0.20 g N-(3-羥基苯基)甲基-苯 並噻唑-6-羧醯胺、0.12 g 1-溴-2-丁炔和5 ml DMF的混合 物中,且混合物在室溫攪拌4小時。將水加到反應混合物 中,和過濾收集所產生的固體。固體依序用氫氧化鈉水溶 液、水和己烷清洗,而得到〇.2〇 g的N-(3-(2-丁炔氧基) 苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (19))。 本發明化合物(19) -55- 201010989 οOCH2CH2CH2CH2CeCH O 'H-NMR (CDC13) δ: 1.68- 1.76 (2H, m), 1.8 8- 1.95 (2H, m), 1.96 (1H, t, J = 2.7 Hz), 2.27 (2H, td, J = 7.0, 2.5 Hz), 3.99 (2H, t, J = 6.3 Hz), 4.66 (2H, d, J = 5.6 Hz), 6.46 (1H, s), 6.84 (1H, dd, J = 8.1, 2.3 Hz) , 6.92-6.96 (2H, m), 7.26-7.30 ( 1 H, m), 7.89 (1H, dd, J = 8.7, 1.7 Hz), 8.17 (1H, d, J = 8.7 Hz), 8.51 (1H, d, J = 1.7 Hz), 9.12 (1H, s). ® Manufacturing Example 19 0.28 g of carbonic acid was added to 0.20 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, A mixture of 0.12 g of 1-bromo-2-butyne and 5 ml of DMF was added and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give N-(3-(2-butynyloxy)phenyl)methyl-benzothiazole-6-carboxamide. (hereinafter referred to as the compound (19) of the present invention). The present invention (19) -55- 201010989 ο
och2c 三 cch3 ^NMR (CDC13)S: 9.12 (1H, s),8.51 (1H,s),8.17 (1H, d, J - 8.5 Hz), 7.89 (1H, d, J = 8.7 Hz), 7.31-7.24 (1H, m), 7.00-6.91 (3H, m), 6.48 (1H, s), 4.68-4.65 (4H, m), 1 .83 (3H, d, J = 1.4 Hz). 製造實例2 0 將0.28 g碳酸鉋加到0.20 g N-(3-羥基苯基)甲基-苯 並唾唑-6-羧醯胺、0.13 g 1-溴-2-戊炔和5 ml DMF的混合Och2c 三cch3 NMR (CDC13)S: 9.12 (1H, s), 8.51 (1H, s), 8.17 (1H, d, J - 8.5 Hz), 7.89 (1H, d, J = 8.7 Hz), 7.31- 7.24 (1H, m), 7.00-6.91 (3H, m), 6.48 (1H, s), 4.68-4.65 (4H, m), 1. .83 (3H, d, J = 1.4 Hz). Manufacturing example 2 0 0.28 g of carbonic acid planer was added to a mixture of 0.20 g of N-(3-hydroxyphenyl)methyl-benzoxazol-6-carboxamide, 0.13 g of 1-bromo-2-pentyne and 5 ml of DMF.
物中,且混合物在室溫攪拌4小時。將水加到反應混合物 中,和過濾收集所產生的固體。固體依序用氫氧化鈉水溶 液、水和己烷清洗,而得到0.21 g的N-(3-(2-戊炔氧基) 苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (20))。And the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The solid was washed successively with aqueous sodium hydroxide solution, water and hexane to give 0.21 g of N-(3-(2-pentynyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as It is the compound (20)) of the present invention.
本發明化合物(20) ΟInventive compound (20) Ο
^^^.OCH2C=CCH2CH3 *H-NMR (CDC13) δ: 9.12 (1Η, s), 8.50 (1H, d, J = 1.7^^^.OCH2C=CCH2CH3 *H-NMR (CDC13) δ: 9.12 (1Η, s), 8.50 (1H, d, J = 1.7
Hz), 8.16 (1H, d, J - 8.5 Hz), 7.89 (1H, dd, J = 8.6, 1.8Hz), 8.16 (1H, d, J - 8.5 Hz), 7.89 (1H, dd, J = 8.6, 1.8
Hz), 7.29 (1H, t, J = 8.2 Hz), 6.99 (2H, d, J = 6.8 Hz),Hz), 7.29 (1H, t, J = 8.2 Hz), 6.99 (2H, d, J = 6.8 Hz),
6.92 (1H, dd, J = 8.0, 2.2 Hz), 6.50 (1H, s), 4.67 (4H, t, J -56- 201010989 =2.3 Hz), 2.21 (2H, tdd, J = 9.9, 5.0, 2.5 Hz), 1.11 (3H, t, J = 7.5 Hz). 製造實例2 16.92 (1H, dd, J = 8.0, 2.2 Hz), 6.50 (1H, s), 4.67 (4H, t, J -56- 201010989 =2.3 Hz), 2.21 (2H, tdd, J = 9.9, 5.0, 2.5 Hz), 1.11 (3H, t, J = 7.5 Hz). Manufacturing Example 2 1
將〇·21 g碳酸鉀加到0.30 g N-(2-氟-3-羥基苯基)甲 基-苯並噻唑-6-羧醯胺、0.16 g卜溴-2-丁炔和5 ml DMF 的混合物中,且混合物在室溫攪拌8小時。將水加到反應 φ 混合物中,且混合物用乙酸乙酯萃取。有機層用飽和食鹽 水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得之殘留 物進行矽膠層析術,而得到0.26 g的N-(2-氟-3-(2-丁炔 氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合 物(21))。 本發明化合物(21)Add 21 g of potassium carbonate to 0.30 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.16 g of bromo-2-butyne and 5 ml of DMF The mixture was stirred and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction φ mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, then dried over magnesium sulfate and evaporated. The obtained residue was subjected to silica gel chromatography to obtain 0.26 g of N-(2-fluoro-3-(2-butynyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is the compound (21)) of the present invention. Inventive Compound (21)
^-NMR (CDC13)5: 1.85 (3H, t, J = 2.3 Hz), 4.72-4.75 (4H, m), 6.58 (1H, s), 7.05-7.07 (3H, m), 7.88 (1H, dd, J = 8.5, 1.7 Hz), 8.16 (1H,d, J = 8.5 Hz), 8.48 (1H, d, J = 1.7 Hz), 9.11 (1H, s). 製造實例22 將0.20 g N-(2-氟-3-羥基苯基)甲基-苯並噻唑-6-羧醯 胺、0.25 g 8-溴-1-辛烯、0.43 g碳酸鉋和3 ml DMF混 -57- 201010989 合,且混合物在室溫攪拌1小時。將水加到反應混合物 中,且混合物用乙酸乙酯萃取。所得之有機層用飽和食鹽 水清洗,接著用無水的硫酸鎂乾燥和在減壓下濃縮。所得 之殘留物進行矽膠層析術,而得到0.16 g的N-(2-氟-3-(7-辛烯氧基)苯基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發 明化合物(22))。 本發明化合物(22) Ο^-NMR (CDC13) 5: 1.85 (3H, t, J = 2.3 Hz), 4.72-4.75 (4H, m), 6.58 (1H, s), 7.05-7.07 (3H, m), 7.88 (1H, dd , J = 8.5, 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.48 (1H, d, J = 1.7 Hz), 9.11 (1H, s). Manufacturing Example 22 0.20 g N-(2 -Fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.25 g 8-bromo-1-octene, 0.43 g carbonate planer and 3 ml DMF mix -57- 201010989, and mixtures Stir at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with brine, then dried over anhydrous magnesium sulfate and evaporated. The residue obtained was subjected to silica gel chromatography to obtain 0.16 g of N-(2-fluoro-3-(7-octenyloxy)phenyl)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is the compound (22)) of the present invention. Inventive Compound (22) Ο
FF
5-^^^N^^V^OCH2CH2CH2CH2CH2CH2CH=CH2 Η Ν- !H-NMR (CDC13) δ: 1.32- 1.52 (6H, m), 1.76-1.84 (2H, m), 2.02-2.08 (2H, m), 3.99 (2H, t, J = 6.5 Hz), 4.70 (2H, d, J = 5.6 Hz), 4.91-5.03 (2H, m), 5.75-5.86 ( 1 H, m), 6.8 5 -6.90 ( 1 H, m), 6.92-7.02 (2H, m), 7.11-7.16 (1H, m), 7.88 (1H, d, J = 8.5 Hz), 8.07 (1H, d, J = 8.5 Hz), 8.44 (1H, s), 9.06 (1H, s). © 製造實例23 將0.20 g N-3-(羥基苯基)甲基-苯並噻唑-6-羧醯胺、 0.27 g 8-溴-1-辛烯、0.46 g碳酸鉋和3 ml DMF混合,且 混合物在室溫攪拌2小時。將水加到反應混合物中’且混 合物用乙酸乙酯萃取。所得之有機層用飽和食鹽水清洗, 接著用無水的硫酸鎂乾燥和在減壓下濃縮。所得之殘留物 進行矽膠層析術,而得到0.13 g的N-(3-(7-辛烯氧基)苯 -58- 201010989 基)甲基-苯並噻唑-6-羧醯胺(下文稱爲本發明化合物 (23))。 本發明化合物(23) Ο5-^^^N^^V^OCH2CH2CH2CH2CH2CH2CH=CH2 Η Ν- !H-NMR (CDC13) δ: 1.32- 1.52 (6H, m), 1.76-1.84 (2H, m), 2.02-2.08 (2H, m ), 3.99 (2H, t, J = 6.5 Hz), 4.70 (2H, d, J = 5.6 Hz), 4.91-5.03 (2H, m), 5.75-5.86 ( 1 H, m), 6.8 5 -6.90 ( 1 H, m), 6.92-7.02 (2H, m), 7.11-7.16 (1H, m), 7.88 (1H, d, J = 8.5 Hz), 8.07 (1H, d, J = 8.5 Hz), 8.44 ( 1H, s), 9.06 (1H, s). © Manufacturing Example 23 0.20 g of N-3-(hydroxyphenyl)methyl-benzothiazole-6-carboxamide, 0.27 g of 8-bromo-1-octyl The olefin, 0.46 g of carbonic acid planer and 3 ml of DMF were mixed, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture' and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous magnesium sulfate The residue obtained was subjected to silica gel chromatography to obtain 0.13 g of N-(3-(7-octenyloxy)benzene-58-201010989)methyl-benzothiazole-6-carboxamide (hereinafter referred to as Is the compound (23)) of the present invention. Inventive compound (23) Ο
ki/\^^〇CH2CH2CH2CH2CH2CH2CH=CH2 'H-NMR (CDC13) δ: 1.35- 1.50 (6H, m), 1.74-1.81 (2H, φ m), 2.02-2.08 (2H, m), 3.95 (2H, t, J = 6.5 Hz), 4.65 (2H, d, J = 5.6 Hz), 4.91-5.02 (2H, m), 5.75-5.86 (1 H, m), 6.58-6.62 (1 H, m), 6.82-6.85 (1 H, m), 6.91 (1H, s), 6.94 (1H, d, J = 7.6 Hz), 7.25-7.29 (1H, m), 7.89 (1H, dd, J = 8.5, 2.0 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.51 (1H, d, J = 1 .7 Hz), 9.11 (1 H, s). 接著,參考製造實例將顯示本發明化合物之中間體的 製造。 參考製造實例1 20 g 3-羥基苯甲醛、200 ml 2-丙醇、16 g吡啶和15 g羥基胺鹽酸鹽的混合物在室溫攪拌3小時。反應混合物 在減壓下濃縮。將水加到殘留物中,且混合物用乙酸乙酯 萃取。有機層依序用5%鹽酸、水和飽和食鹽水清洗,接 著用硫酸鎂乾燥和在減壓下濃縮,得到26 g的3-羥基苯 甲醛肟。 25 g 3-羥基苯甲醛肟、1.3 g的5%鈀碳和300 ml乙 -59- 201010989 醇的混合物在室溫於約1 atm之氫氛圍下攪拌3小時。反 應混合物透過矽鈣石(Celite)(註冊商標)過濾。濾液在減 壓下濃縮。在〇°C混合所得之殘留物、200 ml乙腈和28 g濃鹽酸,和過濾收集所產生的固體。固體用乙腈清洗 和在減壓下乾燥,得到20 g的3-羥基苯甲胺鹽酸鹽。 3-羥基苯甲胺鹽酸鹽。 H3N CI-Ki/\^^〇CH2CH2CH2CH2CH2CH2CH=CH2 'H-NMR (CDC13) δ: 1.35- 1.50 (6H, m), 1.74-1.81 (2H, φ m), 2.02-2.08 (2H, m), 3.95 (2H, t, J = 6.5 Hz), 4.65 (2H, d, J = 5.6 Hz), 4.91-5.02 (2H, m), 5.75-5.86 (1 H, m), 6.58-6.62 (1 H, m), 6.82 -6.85 (1 H, m), 6.91 (1H, s), 6.94 (1H, d, J = 7.6 Hz), 7.25-7.29 (1H, m), 7.89 (1H, dd, J = 8.5, 2.0 Hz) , 8.16 (1H, d, J = 8.5 Hz), 8.51 (1H, d, J = 1.7 Hz), 9.11 (1 H, s). Next, the manufacture of the intermediate of the compound of the present invention will be shown with reference to the production examples. . Reference Production Example 1 A mixture of 20 g of 3-hydroxybenzaldehyde, 200 ml of 2-propanol, 16 g of pyridine and 15 g of hydroxylamine hydrochloride was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% hydrochloric acid, water and brine, and dried over magnesium sulfate and concentrated under reduced pressure to afford 26 g of 3-hydroxybenzaldehyde. A mixture of 25 g of 3-hydroxybenzaldehyde oxime, 1.3 g of 5% palladium on carbon and 300 ml of B-59-201010989 alcohol was stirred at room temperature under a hydrogen atmosphere of about 1 atm for 3 hours. The reaction mixture was filtered through Celite (registered trademark). The filtrate was concentrated under reduced pressure. The resulting residue was mixed at 〇 ° C, 200 ml of acetonitrile and 28 g of concentrated hydrochloric acid, and the resulting solid was collected by filtration. The solid was washed with acetonitrile and dried under reduced pressure to give 20 g of 3-hydroxybenzylamine hydrochloride. 3-hydroxybenzylamine hydrochloride. H3N CI-
!H-NMR (DMSO-d6) δ: 3.89 (2H, q, J = 5.6 Hz), 6.79-6.82 (1H, m), 6.88-6.91 (2H, m), 7.18 (1H, t, J = 7.7 Hz), 8.51 (3H, s), 9.72 (1H, s). 參考製造實例2 使4.5 g 2-氟-3-甲氧基苯甲醇、2.9 ml甲磺醯氯和 50ml THF混合,且混合物在〇°c攪拌。將6.0ml三乙胺 ® 加到混合物中’且混合物在0X:攪拌30分鐘,接著在室 溫攪拌2小時。將乙酸乙酯加到反應混合物中,接著混合 物透過矽鈣石(Celite)(註冊商標)過濾。將水加到濾液 中’且混合物用乙酸乙酯萃取。有機層依序用水及飽和食 鹽水清洗’和用硫酸鎂乾燥,接著在減壓下濃縮,得到 6.9 g的甲磺酸(2-氟-3-甲氧基苯基)甲酯。 甲磺酸(2-氟-3-甲氧基苯基)甲酯 -60- 201010989!H-NMR (DMSO-d6) δ: 3.89 (2H, q, J = 5.6 Hz), 6.79-6.82 (1H, m), 6.88-6.91 (2H, m), 7.18 (1H, t, J = 7.7 Hz), 8.51 (3H, s), 9.72 (1H, s). Reference Production Example 2 4.5 g of 2-fluoro-3-methoxybenzyl alcohol, 2.9 ml of methanesulfonium chloride and 50 ml of THF were mixed, and the mixture was 〇°c stir. 6.0 ml of triethylamine ® was added to the mixture' and the mixture was stirred at 0X for 30 minutes, followed by stirring at room temperature for 2 hours. Ethyl acetate was added to the reaction mixture, and the mixture was filtered through Celite (registered trademark). Water was added to the filtrate' and the mixture was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine and dried over magnesium sulfate, and then concentrated under reduced pressure to afford 6.9 g of (2-fluoro-3-methoxyphenyl)methyl methanesulfonate. (2-fluoro-3-methoxyphenyl)methyl methanesulfonate -60- 201010989
och3 ^-NMR (CDC13) δ: 3.00 (3H, s), 3.91 (3H, s), 5.30 (2H, s), 6.96-7.14 (3H, m). 參考製造實例3 使6.7 g甲磺酸(2_氟-3-甲氧基苯基)甲酯、5.3 g酞 醯亞胺鉀和60 ml DMF混合’且混合物在70°C攪拌4小 時。之後,將水加到反應混合物中,且混合物用乙酸乙醋 萃取。有機層依序用水、稀鹽酸和飽和食鹽水清洗,和用 硫酸鎂乾燥,接著在減壓下濃縮。所得之殘留物用己烷清 洗,得到5.8 g的N-(2-氟-3-甲氧基苯基)甲基酞醯亞胺。 N-(2-氟-3-甲氧基苯基)甲基酞醯亞胺Och3 ^-NMR (CDC13) δ: 3.00 (3H, s), 3.91 (3H, s), 5.30 (2H, s), 6.96-7.14 (3H, m). Reference Production Example 3 6.7 g methanesulfonic acid ( 2_Fluoro-3-methoxyphenyl)methyl ester, 5.3 g of potassium sulfinamide and 60 ml of DMF were mixed' and the mixture was stirred at 70 ° C for 4 hours. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, diluted hydrochloric acid and brine, and dried over magnesium sulfate. The residue obtained was washed with hexane to give 5.8 g of N-(2-fluoro-3-methoxyphenyl)methylimine. N-(2-fluoro-3-methoxyphenyl)methyl quinone imine
*H-NMR (CDCI3) δ: 3.87 (3Η, s), 4.94 (2H, s), 6.86-6.90 (2H, m), 6.98 -7.02 ( 1 H, m), 7.73 (2H, dd, J = 5.4, 3.0 Hz), 7.86 (2H, dd, J = 5.4, 3.0 Hz). 參考製造實例4 將1.63 g肼單水合物滴入至7·7 g N-(2 -氟-3-甲氧基 苯基)甲基酞醯亞胺和30 ml乙醇的混合物中,且混合物 -61 - 201010989 加熱回流4小時。之後,反應混合物冷卻至室溫。將水加 到反應混合物中,且混合物在減壓下濃縮。將稀鹽酸加到 殘留物中,和過濾混合物。將乙酸乙酯加到所得之濾液 中,且將1 5 %氫氧化鈉水溶液加到水層中,直到其Ρ Η達 11。此液體分離成2層。將濃鹽酸加到有機層中,且混合 物在減壓下濃縮,而得到4.5 g的2-氟-3-甲氧基苯甲胺鹽 酸鹽。*H-NMR (CDCI3) δ: 3.87 (3Η, s), 4.94 (2H, s), 6.86-6.90 (2H, m), 6.98 -7.02 ( 1 H, m), 7.73 (2H, dd, J = 5.4, 3.0 Hz), 7.86 (2H, dd, J = 5.4, 3.0 Hz). Reference Production Example 4 1.63 g of hydrazine monohydrate was added dropwise to 7·7 g of N-(2-fluoro-3-methoxy A mixture of phenyl)methylimine and 30 ml of ethanol, and the mixture -61 - 201010989 was heated to reflux for 4 hours. After that, the reaction mixture was cooled to room temperature. Water was added to the reaction mixture, and the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was filtered. Ethyl acetate was added to the obtained filtrate, and a 15% aqueous sodium hydroxide solution was added to the aqueous layer until the enthalpy was reached. This liquid is separated into 2 layers. Concentrated hydrochloric acid was added to the organic layer, and the mixture was concentrated under reduced pressure to give 4.5 g of 2-fluoro-3-methoxybenzylamine hydrochloride.
2-氟-3-甲氧基苯甲胺鹽酸鹽2-fluoro-3-methoxybenzylamine hydrochloride
^-NMR (DMSO-d6) δ: 3.85 (3Η, s), 4.03 (2H, q, J = 5.3 Hz), 7.13-7.23 (3H, m), 8.60 (3H, br s). 參考製造實例5 將24 ml吡啶滴入至1 5.4 g 2-氟-3-甲氧基苯甲醛、 @ 3 0 ml THF和3 ml水的混合溶液中,和在用冰冷卻下,加 入13.8 g羥基胺鹽酸鹽。混合物在室溫攪拌30分鐘。反 應混合物在減壓下濃縮,直到總體積約一半。將水加到混 合物中,且混合物用乙酸乙酯萃取。有機層依序用稀鹽酸 和飽和食鹽水清洗,和用硫酸鎂乾燥,接著在減壓下濃 縮,而得到16 g的2-氟-3-甲氧基苯甲醛肟。 2-氟-3-甲氧基苯甲醛肟 -62- 201010989^-NMR (DMSO-d6) δ: 3.85 (3Η, s), 4.03 (2H, q, J = 5.3 Hz), 7.13-7.23 (3H, m), 8.60 (3H, br s). Reference Manufacturing Example 5 24 ml of pyridine was added dropwise to a mixed solution of 1 5.4 g of 2-fluoro-3-methoxybenzaldehyde, @30 ml of THF and 3 ml of water, and under ice cooling, 13.8 g of hydroxylamine hydrochloride was added. salt. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure until the total volume was about half. Water was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with dilute hydrochloric acid and brine, and dried over magnesium sulfate, and then concentrated under reduced pressure to give 16 g of 2-fluoro-3-methoxybenzaldehyde oxime. 2-fluoro-3-methoxybenzaldehyde oxime -62- 201010989
HONHON
OCH3 ^-NMR (CDCI3) δ: 3.90 (3H, s), 6.96-7.00 ( 1 H, m), 7.03-7.12 (1H, m), 7.30-7.3 3 ( 1 H, m), 7.64-7.78 ( 1 H, m), 8.39 (1H, s). • 參考製造實例6 將12.8 g 2 -氟-3 -甲氧基苯甲醛肟加到2.4 g的10%鈀 碳、8.3 ml的10N鹽酸和200 ml乙醇的混合物中,且混 合物在室溫於約1 atm氫氛圍下攪拌3小時。反應混合物 透過矽鈣石(Celite)(註冊商標)過濾。濾液在減壓下濃 縮,而得到8.2 g的2-氟-3-甲氧基苯甲胺鹽酸鹽。 參考製造實例7 ⑩ 將10 g 2 -氟-3-甲氧基苯甲醛和80 ml乙醇的混合溶 液加到1.8 g的10%鈀碳、1〇 ml水、6.5 ml的10N鹽酸 和50 ml乙醇的混合物中,接著加入5.4 g羥基胺鹽酸 鹽。混合物在室溫攪拌 2小時。此混合物在室溫於約 1 atm氫氛圍下攪拌 3小時。反應混合物透過矽鈣石 (Celite)(註冊商標)過瀘,且濾液在減壓下濃縮。將水加 到殘留物中,且混合物用氯仿萃取。加入1 5%氫氧化鈉水 溶液,直到所得之水層的pH達11,且其用氯仿萃取。有 機層用碳酸鉀乾燥,接著在減壓下濃縮,而得到8.0 g的 -63- 201010989 2-氟-3-甲氧基苯甲胺。 2-氟-3-甲氧基苯甲胺OCH3 ^-NMR (CDCI3) δ: 3.90 (3H, s), 6.96-7.00 ( 1 H, m), 7.03-7.12 (1H, m), 7.30-7.3 3 ( 1 H, m), 7.64-7.78 ( 1 H, m), 8.39 (1H, s). • Reference Manufacturing Example 6 12.8 g of 2-fluoro-3-methoxybenzaldehyde oxime was added to 2.4 g of 10% palladium on carbon, 8.3 ml of 10N hydrochloric acid and 200 In a mixture of ml ethanol, and the mixture was stirred at room temperature under a hydrogen atmosphere of about 1 atm for 3 hours. The reaction mixture was filtered through a solution of Celite (registered trademark). The filtrate was concentrated under reduced pressure to give 8.2 g of 2-fluoro-3-methoxybenzylamine hydrochloride. Reference Production Example 7 10 A mixed solution of 10 g of 2-fluoro-3-methoxybenzaldehyde and 80 ml of ethanol was added to 1.8 g of 10% palladium carbon, 1 ml of water, 6.5 ml of 10N hydrochloric acid and 50 ml of ethanol. The mixture was then added with 5.4 g of hydroxylamine hydrochloride. The mixture was stirred at room temperature for 2 hours. This mixture was stirred at room temperature under a hydrogen atmosphere of about 1 atm for 3 hours. The reaction mixture was passed through a solution of Celite (registered trademark), and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. A 15% aqueous solution of sodium hydroxide was added until the pH of the obtained aqueous layer reached 11 and it was extracted with chloroform. The organic layer was dried over potassium carbonate and then concentrated under reduced pressure to yield s. 2-fluoro-3-methoxybenzylamine
H2NH2N
3 !H-NMR (CDC13) δ: 1.55 (2Η, br s), 3.89 (3H, s), 3.90 (2H, br s), 6.86-6.91 (2H, m), 7.02-7.06 ( 1 H, m). 參考製造實例8 將15 ml的48%氫溴酸加到4 g的2-氟-3-甲氧基苯甲 胺鹽酸鹽中,且混合物加熱回流5小時。讓冷卻至約室溫 之反應混合物在減壓下濃縮,得到4.0 g的2-氟-3-羥基苯 甲胺氫溴酸鹽。 2-氟-3-羥基苯甲胺氫溴酸鹽3 !H-NMR (CDC13) δ: 1.55 (2Η, br s), 3.89 (3H, s), 3.90 (2H, br s), 6.86-6.91 (2H, m), 7.02-7.06 ( 1 H, m Reference Production Example 8 15 ml of 48% hydrobromic acid was added to 4 g of 2-fluoro-3-methoxybenzylamine hydrochloride, and the mixture was heated under reflux for 5 hours. The reaction mixture which was cooled to about room temperature was concentrated under reduced pressure to give 4.0 g of 2-fluoro-3-hydroxybenzamine hydrobromide. 2-fluoro-3-hydroxybenzylamine hydrobromide
H2N HBr ^-NMR (DMSO-d6) δ: 4.04 (2H, q, J = 5.5 Hz), 6.90-6.94 (1H, m), 6.97-7.06 (2H, m), 8.23 (3H, br s), 10.05 (1 H, br s). 參考製造實例9 將7.4 g 2-氟-3-羥基苯甲胺氫溴酸鹽、12.0 g BOP試 劑和1 1.0 g三乙胺加到5.0 g苯並噻唑-6-羧酸和50 ml DMF的混合物中,且混合物在室溫攪拌30分鐘。將水加 201010989 到反應混合物中,且混合物用乙酸乙酯萃取。有機層用飽 和食鹽水清洗,接著用硫酸鎂乾燥和在減壓下濃縮。所得 之殘留物進行矽膠層析術,而得到9.0 g的N-(2-氟-3-羥 基苯基)甲基-苯並噻唑-6-羧醯胺。 N-(2-氟-3-羥基苯基)甲基-苯並噻唑-6-羧醯胺H2N HBr ^-NMR (DMSO-d6) δ: 4.04 (2H, q, J = 5.5 Hz), 6.90-6.94 (1H, m), 6.97-7.06 (2H, m), 8.23 (3H, br s), 10.05 (1 H, br s). Reference Production Example 9 7.4 g of 2-fluoro-3-hydroxybenzidine hydrobromide, 12.0 g of BOP reagent and 1 1.0 g of triethylamine were added to 5.0 g of benzothiazole- A mixture of 6-carboxylic acid and 50 ml of DMF, and the mixture was stirred at room temperature for 30 minutes. Water was added to 201010989 to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue thus obtained was subjected to silica gel chromatography to obtain 9.0 g of N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide. N-(2-fluoro-3-hydroxyphenyl)methyl-benzothiazole-6-carboxyguanamine
Ο FΟ F
!H-NMR (DMSO-d6) δ: 9.78 (1Η, s), 9.54 (1H, s), 9.13 (1H, t, J = 5.7 Hz), 8.70 (1H, d, J = 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.05 (1H, dd, J = 8.5, 1.7 Hz), 6.93 (1H, t, J = 7.8 Hz), 6.87-6.77 (2H, m), 4.53 (2H, d, J = 5.6 Hz). 參考製造實例1 〇 ® 在〇°C,將14gWSC加到lig苯並噻唑-6-羧酸、15 g 3-羥基苯甲胺氫溴酸鹽、20 ml吡啶和150 ml DMF的混 合物中,且混合物在室溫攪拌1小時。將水加到反應混合 物中,且在減壓下餾出溶劑。將水加到殘留物中,和過濾 收集所產生的固體。固體用水和己烷清洗,和在減壓下乾 燥。得到16 g的N-(3-羥基苯基)甲基-苯並噻唑-6-羧醯 胺。 N-(3-羥基苯基)甲基-苯並噻唑-6-羧醯胺 -65- 201010989!H-NMR (DMSO-d6) δ: 9.78 (1Η, s), 9.54 (1H, s), 9.13 (1H, t, J = 5.7 Hz), 8.70 (1H, d, J = 1.7 Hz), 8.16 (1H, d, J = 8.5 Hz), 8.05 (1H, dd, J = 8.5, 1.7 Hz), 6.93 (1H, t, J = 7.8 Hz), 6.87-6.77 (2H, m), 4.53 (2H, d, J = 5.6 Hz). Refer to Manufacturing Example 1 〇® at 〇 ° C, add 14 g of WSC to lig benzothiazole-6-carboxylic acid, 15 g of 3-hydroxybenzylamine hydrobromide, 20 ml of pyridine and In a mixture of 150 ml of DMF, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the solvent was distilled off under reduced pressure. Water was added to the residue, and the resulting solid was collected by filtration. The solid was washed with water and hexane, and dried under reduced pressure. 16 g of N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxamide was obtained. N-(3-hydroxyphenyl)methyl-benzothiazole-6-carboxyguanamine -65- 201010989
:〇Λ *H-NMR (DMSO-d6) δ: 4.45 (2H, d, J = 5.9 Hz), 6.64 (1H, dd, J = 7.2, 1.6 Hz), 6.76-6.77 (2H, m), 7.12 (1H, t, J = 8.0 Hz), 8.06 (1H, dd, J = 8.5, 1.7 Hz), 8.17 (1H, d, J =8.5 Hz), 8.71 (1H, d, J = 1.7 Hz), 9.15 (1H, t, J = 5.9 Hz), 9.33 (1H, s), 9.54 (1H, s). 接著,下面顯示製劑實例。份數以重量表示。 製劑實例1 硏磨和徹底混合50份的本發明之化合物(i)至(23)中 之一者、3份的木質素磺酸鈣、2份的十二烷基硫酸鎂和 4 5份的合成水合氧化砂,得到可濕性粉劑. 製劑實例2 φ 使20份的本發明之化合物(1)至(23)中之一者和1.5 份的三油酸山梨醇酐酯與2 8.5份的含有2份聚乙烯醇之 水溶液混合,且混合物經由濕硏磨法而予以微細地硏磨, 接著加入40份的含有0.05份三仙膠和〇.1份矽酸鋁鎂之 水溶液,和另外地,加入10份的丙二醇且攪拌混合,得 到流性物。 製劑實例3 -66 - 201010989 硏磨和徹底混合2份的本發明之化合物(1)至(23)中之 一者、88份的高嶺土和1〇份的滑石,得到粉劑。 製劑實例4 徹底混合5份的本發明之化合物(1)至(23)中之一者、 14份的聚氧乙烯苯乙烯苯基醚、6份的十二烷基苯磺酸鈣 和75份的二甲苯,得到乳劑。 製劑實例5 硏磨和徹底混合2份的本發明之化合物(1)至(23)中之 —者、1份的合成水合氧化矽、2份的木質素磺酸鈣、30 份的膨潤土和65份的高嶺土,接著加入水,且混合物被 徹底揉合、顆粒化和乾燥,得到顆粒。 製劑實例6 Φ 混合和藉由濕硏磨法微細地硏磨10份的本發明之化 合物(1)至(2 3)中之一者、50份的聚氧乙烯烷基醚硫酸銨 鹽、3 5份的白碳和5 5份的水,得到製劑。 接著,試驗實例將顯示,本發明化合物對防治植物疾 病是有用的。 防治效果係經由下述而予以評估:視覺上觀察硏究中 之目標植物的疾病斑的面積,和比較用本發明化合物治療 植物的疾病斑的面積與未經治療的植物的疾病斑的面積。 於試驗中一起使用N-(2-甲氧基苯基)甲基-苯並噻唑- -67- 201010989 6-羧醯胺(下式(A)之化合物。下文稱爲比較化合物(A))作 爲對照組。: 〇Λ *H-NMR (DMSO-d6) δ: 4.45 (2H, d, J = 5.9 Hz), 6.64 (1H, dd, J = 7.2, 1.6 Hz), 6.76-6.77 (2H, m), 7.12 (1H, t, J = 8.0 Hz), 8.06 (1H, dd, J = 8.5, 1.7 Hz), 8.17 (1H, d, J = 8.5 Hz), 8.71 (1H, d, J = 1.7 Hz), 9.15 (1H, t, J = 5.9 Hz), 9.33 (1H, s), 9.54 (1H, s). Next, an example of the formulation is shown below. The number of parts is expressed by weight. Formulation Example 1 honing and thoroughly mixing 50 parts of one of the compounds (i) to (23) of the present invention, 3 parts of calcium lignosulfonate, 2 parts of magnesium lauryl sulfate, and 45 parts of Synthetic hydrated oxidized sand to obtain a wettable powder. Formulation Example 2 φ 20 parts of one of the compounds (1) to (23) of the present invention and 1.5 parts of sorbitan trioleate and 2 8.5 parts An aqueous solution containing 2 parts of polyvinyl alcohol is mixed, and the mixture is finely honed by wet honing, followed by adding 40 parts of an aqueous solution containing 0.05 parts of celestial gum and 1 part of aluminum magnesium silicate, and additionally 10 parts of propylene glycol was added and stirred to obtain a fluid. Formulation Example 3 - 66 - 201010989 Two parts of the compound (1) to (23) of the present invention, 88 parts of kaolin clay and 1 part by weight of talc were honed and thoroughly mixed to obtain a powder. Formulation Example 4 5 parts of one of the compounds (1) to (23) of the present invention, 14 parts of polyoxyethylene styrene phenyl ether, 6 parts of calcium dodecylbenzene sulfonate and 75 parts were thoroughly mixed. The xylene is obtained as an emulsion. Formulation Example 5 honing and thoroughly mixing 2 parts of the compounds (1) to (23) of the present invention, 1 part of synthetic hydrated cerium oxide, 2 parts of calcium lignosulfonate, 30 parts of bentonite and 65 The kaolin is then added with water, and the mixture is thoroughly kneaded, granulated and dried to obtain granules. Formulation Example 6 Φ mixing and finely honing 10 parts of one of the compounds (1) to (2 3) of the present invention by wet honing, 50 parts of polyoxyethylene alkyl ether ammonium sulfate, 3 5 parts of white carbon and 5 parts of water were obtained to obtain a preparation. Next, test examples will show that the compounds of the present invention are useful for controlling plant diseases. The control effect was evaluated by visually observing the area of the disease spot of the target plant in the study, and comparing the area of the disease spot of the plant treated with the compound of the present invention with the area of the disease spot of the untreated plant. N-(2-methoxyphenyl)methyl-benzothiazole--67-201010989 6-carboxamide (the compound of the following formula (A). Hereinafter referred to as comparative compound (A)) was used together in the test. As a control group.
試驗實例1 塑膠盆塡塞砂壤土,種入黃瓜(植物品種;Sagarni Hanjiro),且在溫室生長12天。本發明化合物(2)、(3)、 φ (5)、(7)、(13)、(14)、(15)和(17)依據製劑實例6予以調 製,調合物用水稀釋,使得活性成分的濃度爲500 ppm。 此稀釋液體噴灑在莖和葉子上,以便充分地黏著至黃瓜的 葉表面。噴灑之後,植物經空氣乾燥,且將含有灰黴病菌 (Botrytis cinerea)孢子之PDA培養液安置於黃瓜的葉表面 上。接種之後,處於在12 °C於潮濕條件下達5天,接著 檢查疾病斑面積。結果是:經本發明化合物(2)、(3)、 (5)、(7)、(13)、(14)、(15)和(17)處理之植物的疾病斑面 〇 積爲未經處理之植物的疾病斑面積的10 %或更少。 試驗實例2 塑膠盆塡塞砂壤土,種入黃瓜(植物品種;Sagami Hanjiro),且在溫室生長12天。本發明化合物(1)至(21) 和比較化合物(A)依據製劑實例6予以調製,調合物用水 稀釋,使得活性成分的濃度爲500 ppm。此稀釋液體噴灑 在莖和葉子上,以便充分地黏著至黃瓜的葉表面。噴灑之 -68- 201010989 後’植物經空氣乾燥 > 且將含有菌核病菌(Sclerotinia sclerotiorum)菌絲之PDA培養液安置於黃瓜的葉表面上。 接種之後,處於在18 °C於潮濕條件下達4天,接著檢査 疾病斑面積。結果是:經本發明化合物(1)至(21)處理之植 物的疾病斑面積爲未經處理之植物的疾病斑面積的10 %或 更少。經比較化合物(A)處理之植物的疾病斑面積爲未經 處理之植物的疾病斑面積的76至100%。 β 試驗實例3 塑膠盆塡塞苗床土肥,種入稻作(植物品種; Nihonbare),且在溫室生長12天。本發明化合物(1)、(5) 至(7)、(12)至(16)和(21)依據製劑實例6予以調製,調合 物用水稀釋,使得活性成分的濃度爲500 ppm。此稀釋液 體噴灑在莖和葉子上,以便充分地黏著至稻作的葉表面。 噴灑之後,植物經空氣乾燥,且具有被稻熱病菌 β (Magnaporthe grisea)影響之葉子的盆圍繞經噴灑的植物放 置。所有稻作植物僅在晚上置於潮濕條件下,且在接種後 5天,檢查疾病斑面積。結果是:經本發明化合物(1)、(5) 至(7)、(12)至(16)和(2 1)處理之植物的疾病斑面積爲未經 處理之植物的疾病斑面積的10%或更少。 產業利用性 本發明化合物對作爲植物疾病防治組成物中之活性成 分是有用的,因爲化合物具有植物疾病防治效果。 -69-Test Example 1 A plastic pot was stuffed with sandy loam soil, planted with cucumber (plant variety; Sagarni Hanjiro), and grown in the greenhouse for 12 days. The compounds (2), (3), φ (5), (7), (13), (14), (15) and (17) of the present invention are prepared according to Formulation Example 6, and the mixture is diluted with water to make the active ingredient The concentration is 500 ppm. This diluted liquid is sprayed on the stems and leaves so as to adhere sufficiently to the leaf surface of the cucumber. After spraying, the plants were air-dried, and a PDA medium containing spores of Botrytis cinerea was placed on the leaf surface of the cucumber. After inoculation, it was exposed to humid conditions at 12 °C for 5 days, and then the disease spot area was examined. As a result, the disease plaque of the plants treated with the compounds (2), (3), (5), (7), (13), (14), (15) and (17) of the present invention was untreated. The disease area of the plant is 10% or less. Test Example 2 A plastic pot was stuffed with sandy loam soil, planted with cucumber (plant variety; Sagami Hanjiro), and grown in the greenhouse for 12 days. The compounds (1) to (21) and the comparative compound (A) of the present invention were prepared in accordance with Formulation Example 6, and the mixture was diluted with water so that the concentration of the active ingredient was 500 ppm. This diluted liquid is sprayed on the stems and leaves so as to adhere sufficiently to the leaf surface of the cucumber. After spraying -68-201010989, the plants were air-dried > and the PDA medium containing the hyphae of Sclerotinia sclerotiorum was placed on the leaf surface of the cucumber. After inoculation, it was exposed to humid conditions at 18 °C for 4 days, and then the disease spot area was examined. As a result, the disease spot area of the plants treated with the compounds (1) to (21) of the present invention was 10% or less of the disease spot area of the untreated plants. The disease spot area of the plant treated with the comparative compound (A) was 76 to 100% of the disease spot area of the untreated plant. β Test Example 3 Plastic pots were used to soil the soil, planted in rice (plant variety; Nihonbare), and grown in the greenhouse for 12 days. The compounds (1), (5) to (7), (12) to (16) and (21) of the present invention were prepared according to Formulation Example 6, and the blend was diluted with water so that the concentration of the active ingredient was 500 ppm. This diluted liquid is sprayed on the stems and leaves so as to adhere sufficiently to the leaf surface of the rice. After spraying, the plants were air-dried and pots with leaves affected by rice heat bacteria β (Magnaporthe grisea) were placed around the sprayed plants. All rice plants were placed in humid conditions only at night, and the disease spot area was examined 5 days after inoculation. As a result, the disease spot area of the plants treated with the compounds (1), (5) to (7), (12) to (16) and (2 1) of the present invention is 10% of the disease spot area of the untreated plants. Or less. Industrial Applicability The compound of the present invention is useful as an active ingredient in a plant disease control composition because the compound has a plant disease control effect. -69-
Claims (1)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008163050 | 2008-06-23 | ||
JP2008163047 | 2008-06-23 | ||
JP2008163049 | 2008-06-23 | ||
JP2008163048 | 2008-06-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
TW201010989A true TW201010989A (en) | 2010-03-16 |
Family
ID=40941297
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW98119052A TW201010989A (en) | 2008-06-23 | 2009-06-08 | Amide compound and use thereof |
Country Status (4)
Country | Link |
---|---|
JP (1) | JP2010030990A (en) |
AR (1) | AR072266A1 (en) |
TW (1) | TW201010989A (en) |
WO (1) | WO2009157528A1 (en) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7932272B2 (en) * | 2003-09-30 | 2011-04-26 | Eisai R&D Management Co., Ltd. | Antifungal agent containing heterocyclic compound |
ES2325523B1 (en) * | 2007-03-22 | 2010-06-24 | Sumitomo Chemical Company, Limited | AGRICULTURAL COMPOSITION TO CONTROL OR PREVENT DISEASES OF PLANTS CAUSED BY PATHOGRAPHIC MICROBIES OF PLANTS. |
-
2009
- 2009-06-08 TW TW98119052A patent/TW201010989A/en unknown
- 2009-06-17 JP JP2009144020A patent/JP2010030990A/en active Pending
- 2009-06-19 AR ARP090102267 patent/AR072266A1/en unknown
- 2009-06-19 WO PCT/JP2009/061670 patent/WO2009157528A1/en active Application Filing
Also Published As
Publication number | Publication date |
---|---|
WO2009157528A1 (en) | 2009-12-30 |
AR072266A1 (en) | 2010-08-18 |
JP2010030990A (en) | 2010-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2010077118A (en) | Amide compound and application thereof | |
JP2010077117A (en) | Amide compound and application thereof for plant disease control | |
US9309191B2 (en) | Amidine compound and use thereof | |
US20130296436A1 (en) | Amidine compounds and use thereof for plant disease control | |
AU2008239225A1 (en) | Agricultural composition for controlling or preventing plant diseases | |
JP2010270034A (en) | Amide compound, and use therefor in controlling plant disease | |
EP2174931A1 (en) | Amide compound and method for controlling plant disease using the same | |
JP2013151432A (en) | Plant disease control composition and application of the same | |
JP2011001294A (en) | Amide compound and application thereof for controlling plant disease | |
EP2222655B1 (en) | N-cycl0alkylmethyl-2-amin0thiaz0le-5-carb0xamides for use in plant disease control | |
JP2011001292A (en) | Amide compound and application thereof | |
WO2009110542A1 (en) | Anilide compound and use thereof | |
TW201010989A (en) | Amide compound and use thereof | |
JP2010030989A (en) | Amide compound, and its use in controlling plant disease | |
JP2011246380A (en) | Pyridazine compound and use thereof | |
JP2011001293A (en) | Amide compound and application thereof for controlling plant disease | |
JP2009173589A (en) | Amide compound and use thereof for controlling vegetable disease | |
JP2010285352A (en) | Amide compound and use thereof | |
JP2009256263A (en) | Amide compound and its use for plant disease control | |
JP2009173590A (en) | Amide compound and use thereof for controlling vegetable disease | |
JP2009173591A (en) | Amide compound and use thereof for controlling vegetable disease | |
JP2011001291A (en) | Amide compound and application thereof for controlling plant disease | |
JP2010270035A (en) | Amide compound, and use therefor in controlling plant disease | |
JP2009173592A (en) | Amide compound and use thereof for controlling vegetable disease | |
JP2010270037A (en) | Amide compound, and agent for controlling plant disease comprising the same |