JPH0812657A - Production of triazole derivative and its intermediate - Google Patents
Production of triazole derivative and its intermediateInfo
- Publication number
- JPH0812657A JPH0812657A JP6167423A JP16742394A JPH0812657A JP H0812657 A JPH0812657 A JP H0812657A JP 6167423 A JP6167423 A JP 6167423A JP 16742394 A JP16742394 A JP 16742394A JP H0812657 A JPH0812657 A JP H0812657A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- triazole
- group
- lower alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、殺虫、殺ダニ剤の中間
原料として有用なトリアゾール誘導体の製造法およびそ
の中間体に関するものである。TECHNICAL FIELD The present invention relates to a process for producing a triazole derivative useful as an intermediate raw material for insecticides and acaricides, and an intermediate thereof.
【０００２】[0002]
【従来の技術】ある種のフェニルトリアゾール誘導体が
ルイス酸触媒存在下、ヒドラゾン誘導体とニトリル誘導
体から製造できることはすでに知られている（Bull.Che
m.Soc.Jap.,56,545-548(1983)）。しかし、この方法は
塩化アルミニウム等を用いる反応条件下で分解してしま
う保護基を有する原料化合物や反応に活性な置換基を持
つ原料化合物への適用が困難である。2. Description of the Related Art It is already known that certain phenyltriazole derivatives can be produced from hydrazone derivatives and nitrile derivatives in the presence of Lewis acid catalysts (Bull.
m.Soc. Jap., 56 , 545-548 (1983)). However, this method is difficult to be applied to a raw material compound having a protective group that decomposes under reaction conditions using aluminum chloride or the like, or a raw material compound having a substituent active in the reaction.
【０００３】一方、さらに置換されたヒドロキシメチル
基を置換基として有するフェニルトリアゾール誘導体が
殺虫剤として有用である事が提案されている（特願平５
−１３２４３１号公報）。また、ヒドロキシメチルフェ
ニル基を有するトリアゾール誘導体の製造法は、このも
のが殺虫、殺ダニ剤の中間原料となることと共に既に提
案されている（特願平６−９７９４６）。しかし、該公
報においてヒドロキシメチルフェニル基を有するトリア
ゾール誘導体の製造は前記文献記載の方法ではなく上記
のごときヒドロキシメチル基の保護の問題は生じない代
わりに煩雑で工程数が多く工業的実施には不利な方法、
すなわちトリアゾール環を形成した後さらに３工程をか
けてヒドロキシメチル基を形成する方法で行われてい
る。このような背景から、このヒドロキシメチルフェニ
ル基を有するトリアゾール誘導体を簡便かつ工業的に製
造するのに適した方法の出現が望まれていた。On the other hand, it has been proposed that a phenyltriazole derivative having a further substituted hydroxymethyl group as a substituent is useful as an insecticide (Japanese Patent Application No. Hei.
-132431). Further, a method for producing a triazole derivative having a hydroxymethylphenyl group has already been proposed along with the fact that this is an intermediate raw material for insecticides and acaricides (Japanese Patent Application No. 6-97946). However, the production of the triazole derivative having a hydroxymethylphenyl group in this publication is not the method described in the above literature, but the problem of protection of the hydroxymethyl group as described above does not occur, but it is complicated and many steps are disadvantageous for industrial implementation. No way,
That is, it is carried out by a method of forming a hydroxymethyl group by further forming three steps after forming a triazole ring. From such a background, the advent of a method suitable for conveniently and industrially producing the triazole derivative having the hydroxymethylphenyl group has been desired.
【０００４】[0004]
【発明が解決しようとする課題】本発明は上記問題点を
解決した、ヒドロキシメチルフェニル基を有するトリア
ゾール誘導体の効率的な製造法およびその中間体の提供
を目的とする。SUMMARY OF THE INVENTION It is an object of the present invention to provide a method for efficiently producing a triazole derivative having a hydroxymethylphenyl group and an intermediate thereof, which solves the above problems.
【０００５】[0005]
【課題を解決するための手段】本発明者らは上記課題を
解決すべく鋭意研究を重ねた。その結果、意外にもヒド
ラゾン誘導体とシアノ基を有する安息香酸エステルとを
用いてトリアゾール環形成反応を行う際に、ルイス酸と
して塩化第二鉄を用いた場合にのみ収率よくアルコキシ
カルボニルフェニルトリアゾール誘導体が得られるこ
と、該アルコキシカルボニルフェニルトリアゾール誘導
体は文献未記載の新規化合物であること、該アルコキシ
カルボニルフェニル基を有するトリアゾール化合物の持
つエステル基を還元することにより容易にヒドロキシメ
チルフェニル基を有するトリアゾール誘導体へと誘導で
きること等を見いだし、これらの知見に基づき本発明を
完成した。Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems. As a result, surprisingly, when a triazole ring-forming reaction is performed using a hydrazone derivative and a benzoic acid ester having a cyano group, the yield of the alkoxycarbonylphenyltriazole derivative is good only when ferric chloride is used as the Lewis acid. That the alkoxycarbonylphenyltriazole derivative is a novel compound not described in the literature, and the triazole derivative having a hydroxymethylphenyl group can be easily obtained by reducing the ester group of the alkoxycarbonylphenyl group-containing triazole compound. The present invention has been completed based on these findings.
【０００６】即ち、本発明は下記（１）〜（３）記載の
事項を提供する。That is, the present invention provides the following items (1) to (3).
【０００７】（１）一般式(1) General formula
【０００８】[0008]
【化８】 （式中、ＸおよびＹは各々独立にハロゲン原子を示し、
Ｒ1、Ｒ3は各々独立に低級アルキル基を示す。）Embedded image (In the formula, X and Y each independently represent a halogen atom,
R 1 and R 3 each independently represent a lower alkyl group. )
【０００９】で表わされるヒドラゾン誘導体と一般式A hydrazone derivative represented by
【００１０】[0010]
【化９】 （式中、Ｒ2は低級アルキル基を示す。）[Chemical 9] (In the formula, R 2 represents a lower alkyl group.)
【００１１】で表されるシアノ安息香酸エステルとを塩
化第二鉄の存在下で反応させて一般式A cyanobenzoic acid ester represented by the following formula is reacted in the presence of ferric chloride to give a compound of the general formula
【００１２】[0012]
【化１０】 （式中、Ｘ、Ｙ、Ｒ1およびＲ2は前記と同じ意味を示
す。）[Chemical 10] (In the formula, X, Y, R 1 and R 2 have the same meanings as described above.)
【００１３】で表されるアルコキシカルボニルフェニル
トリアゾール誘導体を得た後、さらにこれを還元するこ
とを特徴とする、一般式After obtaining an alkoxycarbonylphenyltriazole derivative represented by the formula:
【００１４】[0014]
【化１１】 （式中、Ｘ、ＹおよびＲ1は前記と同じ意味を示す。）[Chemical 11] (In the formula, X, Y and R 1 have the same meanings as described above.)
【００１５】で表されるヒドロキシメチルフェニルトリ
アゾール誘導体を製造する方法。A method for producing a hydroxymethylphenyltriazole derivative represented by:
【００１６】（２）（１）項記載の一般式（ＩＩＩ）で
表されるアルコキシカルボニルフェニルトリアゾール誘
導体。(2) An alkoxycarbonylphenyltriazole derivative represented by the general formula (III) described in (1).
【００１７】（３）一般式(3) General formula
【００１８】[0018]
【化１２】 （式中、ＸおよびＹは各々独立にハロゲン原子を示し、
Ｒ1、Ｒ3は各々独立に低級アルキル基を示す。）[Chemical 12] (In the formula, X and Y each independently represent a halogen atom,
R 1 and R 3 each independently represent a lower alkyl group. )
【００１９】で表わされるヒドラゾン誘導体と一般式The hydrazone derivative represented by and the general formula
【００２０】[0020]
【化１３】 （式中、Ｒ2は低級アルキル基を示す。）[Chemical 13] (In the formula, R 2 represents a lower alkyl group.)
【００２１】で表されるシアノ安息香酸エステルとを塩
化第二鉄の存在下で反応させることを特徴とする一般式A general formula characterized by reacting a cyanobenzoate represented by
【００２２】[0022]
【化１４】 （式中、Ｘ、Ｙ、Ｒ1およびＲ2は前記と同じ意味を示
す。）Embedded image (In the formula, X, Y, R 1 and R 2 have the same meanings as described above.)
【００２３】で表されるアルコキシカルボニルフェニル
トリアゾール誘導体の製造方法。A method for producing an alkoxycarbonylphenyltriazole derivative represented by:
【００２４】以下に、本発明を詳細に説明する。The present invention will be described in detail below.
【００２５】下記フロー（化１５）は本発明の概略を示
すものである。The following flow (Formula 15) shows an outline of the present invention.
【００２６】[0026]
【化１５】 （式中、ＸおよびＹは各々独立にハロゲン原子を示し、
Ｒ1、Ｒ2およびＲ3は各々独立に低級アルキル基を示
す。）[Chemical 15] (In the formula, X and Y each independently represent a halogen atom,
R 1 , R 2 and R 3 each independently represent a lower alkyl group. )
【００２７】本発明方法では、まず、一般式（Ｉ）で表
されるヒドラゾン誘導体（以下、単に「化合物（Ｉ）」
と記載することがある。）と一般式（ＩＩ）で表される
シアノ安息香酸エステル類（以下、単に「化合物（Ｉ
Ｉ）」と記載することがある。）とを塩化第二鉄の存在
下で反応させて、一般式（ＩＩＩ）で表されるアルコキ
シカルボニルフェニルトリアゾール誘導体（以下、単に
「化合物（ＩＩＩ）」と記載することがある。）を製造
する。この工程には塩化第二鉄のみがアルコキシカルボ
ニル基の分解等を起こさず目的物製造に有効な触媒とし
て使用可能であることを本発明者らが見出したものであ
る。In the method of the present invention, first, a hydrazone derivative represented by the general formula (I) (hereinafter, simply referred to as "compound (I)").
May be described as. ) And cyanobenzoic acid esters represented by the general formula (II) (hereinafter, simply referred to as “compound (I
I) ". ) In the presence of ferric chloride to produce an alkoxycarbonylphenyltriazole derivative represented by the general formula (III) (hereinafter sometimes simply referred to as “compound (III)”). . The present inventors have found that in this step, ferric chloride alone can be used as an effective catalyst for the production of the target product without causing decomposition of the alkoxycarbonyl group.
【００２８】本発明方法における塩化第二鉄の使用量は
化合物（Ｉ）に対して１０モル％〜２００モル％、好ま
しくは５０モル％〜１２０モル％である。The amount of ferric chloride used in the method of the present invention is 10 mol% to 200 mol%, preferably 50 mol% to 120 mol% based on the compound (I).
【００２９】原料として使用する化合物（Ｉ）として
は、一般式（Ｉ）で表されるヒドラゾン誘導体なら使用
してさしつかえない。ここで式中の置換基ＸおよびＹと
してはフッ素原子、塩素原子、臭素原子、ヨウ素原子等
のハロゲン原子を、置換基Ｒ1およびＲ3としてはメチル
基、エチル基、ｎ−プロピル基、ｉ−プロピル基、ｎ−
ブチル基、ｉ−ブチル基、ｔ−ブチル基、ｓｅｃ−ブチ
ル基、ｎ−ペンチル基、ｎ−ヘキシル基、シクロヘキシ
ル基等を包含する直鎖、分岐鎖あるいは環構造を有して
もよい低級アルキル基を、それぞれの置換基の具体例と
して例示できる。As the compound (I) used as a raw material, any hydrazone derivative represented by the general formula (I) may be used. Here, as the substituents X and Y in the formula, a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom is used, and as the substituents R 1 and R 3 , a methyl group, an ethyl group, an n-propyl group, i -Propyl group, n-
Lower alkyl which may have a linear, branched or cyclic structure including a butyl group, i-butyl group, t-butyl group, sec-butyl group, n-pentyl group, n-hexyl group, cyclohexyl group and the like. A group can be illustrated as a specific example of each substituent.
【００３０】また、化合物（ＩＩ）としては、一般式
（ＩＩ）で表わされる４−シアノ安息香酸エステル類な
ら使用しても良い。ここで式中の置換基Ｒ2としては前
記化合物（Ｉ）の置換基Ｒ1およびＲ3と同様のメチル
基、エチル基、ｎ−プロピル基、ｉ−プロピル基、ｎ−
ブチル基、ｉ−ブチル基、ｔ−ブチル基、ｓｅｃ−ブチ
ル基、ｎ−ペンチル基、ｎ−ヘキシル基、シクロヘキシ
ル基等を包含する直鎖、分岐鎖、あるいは環構造を有し
てもよい低級アルキル基を具体例として例示できる。化
合物（ＩＩ）の使用量は化合物（Ｉ）に対して８０モル
％〜１２０モル％、好ましくは９５モル％〜１０５モル
％の範囲を例示できる。As the compound (II), 4-cyanobenzoic acid esters represented by the general formula (II) may be used. Here, as the substituent R 2 in the formula, the same methyl group, ethyl group, n-propyl group, i-propyl group and n-group as the substituents R 1 and R 3 of the compound (I) are used.
Lower that may have a linear, branched, or cyclic structure including a butyl group, an i-butyl group, a t-butyl group, a sec-butyl group, an n-pentyl group, an n-hexyl group, a cyclohexyl group, and the like. An alkyl group can be illustrated as a specific example. The amount of the compound (II) used may be, for example, 80 mol% to 120 mol%, preferably 95 mol% to 105 mol% with respect to the compound (I).
【００３１】溶媒は反応に不活性な溶媒であれば使用し
てよく、例えばクロロベンゼン、ジクロロベンゼン等の
芳香族ハロゲン化炭化水素系溶媒、ニトロベンゼン、ク
ロロニトロベンゼン等の芳香族ニトロ化合物を例示で
き、その使用量は化合物（Ｉ）に対し３００ml／モル〜
３０００ml／モル、好ましくは５００ml／モル〜１００
０ml／モルの範囲を例示できる。As the solvent, any solvent inert to the reaction may be used. Examples thereof include aromatic halogenated hydrocarbon solvents such as chlorobenzene and dichlorobenzene, and aromatic nitro compounds such as nitrobenzene and chloronitrobenzene. The amount used is 300 ml / mol to compound (I).
3000 ml / mol, preferably 500 ml / mol-100
A range of 0 ml / mol can be exemplified.
【００３２】反応は９０℃〜１８０℃、好ましくは１１
０℃〜１４０℃の温度範囲で、通常は５時間〜１０時間
行えばよい。The reaction is 90 ° C to 180 ° C, preferably 11 ° C.
It may be carried out in a temperature range of 0 ° C. to 140 ° C., usually for 5 hours to 10 hours.
【００３３】この工程で得られる化合物（ＩＩＩ）は文
献未記載の新規化合物で、前記（２）項記載の本発明化
合物である。化合物（ＩＩＩ）は殺虫、殺ダニ剤として
有用なトリアゾール誘導体の重要な製造中間体であり、
化合物（ＩＩＩ）提供可能になったことにより本発明方
法も提供が可能となった。The compound (III) obtained in this step is a novel compound not described in the literature and is the compound of the present invention described in the above item (2). Compound (III) is an important intermediate for the production of triazole derivatives useful as insecticides and acaricides,
Since the compound (III) can be provided, the method of the present invention can also be provided.
【００３４】次いで、ヒドロキシメチルフェニル基を有
するトリアゾール誘導体（以下、単に「化合物（Ｉ
Ｖ）」と記載することがある。）を製造する方法につい
て説明する。この工程は先の工程で得た化合物（ＩＩ
Ｉ）を還元することによって目的とする化合物（ＩＶ）
を製造するものである。Next, a triazole derivative having a hydroxymethylphenyl group (hereinafter referred to simply as "compound (I
V) ". ) Will be described. This step corresponds to the compound (II
Compound (IV) of interest by reducing I)
Is to manufacture.
【００３５】化合物（ＩＩＩ）の還元は通常は還元剤に
より行われ、この目的にに使用できる還元剤としては、
水素化ホウ素ナトリウム、水素化リチウムアルミニウム
等の金属水素錯化合物を例示できる。その使用量は化合
物（ＩＩＩ）に対して９０モル％〜５００モル％、好ま
しくは１２０モル％〜３００モル％の範囲を例示でき
る。The reduction of compound (III) is usually carried out with a reducing agent, and as a reducing agent usable for this purpose,
Examples thereof include metal hydrogen complex compounds such as sodium borohydride and lithium aluminum hydride. The amount thereof used may be, for example, 90 mol% to 500 mol%, preferably 120 mol% to 300 mol% with respect to the compound (III).
【００３６】溶媒はアルコール類、例えばメタノール、
エタノール、プロパノール、ブタノール等を例示でき、
その使用量は化合物（ＩＩＩ）に対し５００ｍｌ／モル
〜２０００ｍｌ／モル、好ましくは８００ｍｌ／モル〜
１３００ｍｌ／モルの範囲を例示できる。The solvent is an alcohol such as methanol,
Examples include ethanol, propanol, butanol,
The amount used is 500 ml / mol to 2000 ml / mol, preferably 800 ml / mol to compound (III).
A range of 1300 ml / mol can be exemplified.
【００３７】反応は２０℃〜８０℃、好ましくは４０℃
〜６０℃の温度範囲で、通常は２４時間〜３６時間行え
ばよい。The reaction temperature is 20 ° C to 80 ° C, preferably 40 ° C.
It may be carried out in the temperature range of -60 ° C for 24 hours to 36 hours.
【００３８】この工程により得られる、本発明方法の目
的とする化合物（ＩＶ）は新規化合物であって前記公報
に記載のある方法に準じて水酸基を修飾することにより
簡便に種々の誘導体へ誘導できるため、前記殺虫、殺ダ
ニ剤の製造中間体として汎用性が高くきわめて重要であ
る。The compound (IV), which is the object of the method of the present invention, obtained by this step is a novel compound and can be easily derived into various derivatives by modifying the hydroxyl group according to the method described in the above publication. Therefore, it is extremely versatile and extremely important as a production intermediate for the insecticide and acaricide.
【００３９】なお、先に本発明方法の重要中間体として
記載した本発明の化合物（ＩＩＩ）の具体例としては３
−（２−クロロ−６−フルオロフェニル）−５−（４−
メトキシカルボニルフェニル）−１−メチル−１Ｈ−
１，２，４−トリアゾール、３−（２，６−ジクロロフ
ェニル）−５−（４−エトキシカルボニルフェニル）−
１−メチル−１Ｈ−１，２，４−トリアゾール、３−
（２，６−ジブロモフェニル）−５−（４−イソプロポ
キシカルボニルフェニル）−１−メチル−１Ｈ−１，
２，４−トリアゾール、３−（２，６−ジフルオロフェ
ニル）−５−（４−メトキシカルボニルフェニル）−１
−エチル−１Ｈ−１，２，４−トリアゾール、３−
（２，６−ジクロロフェニル）−５−（４−シクロヘキ
シルオキシカルボニルフェニル）−１−メチル−１Ｈ−
１，２，４−トリアゾール、３−（２，６−ジブロモフ
ェニル）−５−（４−ブトキシカルボニルフェニル）−
１−メチル−１Ｈ−１，２，４−トリアゾール、３−
（２，６−ジフルオロフェニル）−５−（４−メトキシ
カルボニルフェニル）−１−ブチル−１Ｈ−１，２，４
−トリアゾール、３−（２−ブロモ−６−クロロフェニ
ル）−５−（４−メトキシカルボニルフェニル）−１−
シクロヘキシル−１Ｈ−１，２，４−トリアゾール等を
例示できる。Specific examples of the compound (III) of the present invention described above as the important intermediate of the method of the present invention are 3
-(2-chloro-6-fluorophenyl) -5- (4-
Methoxycarbonylphenyl) -1-methyl-1H-
1,2,4-triazole, 3- (2,6-dichlorophenyl) -5- (4-ethoxycarbonylphenyl)-
1-methyl-1H-1,2,4-triazole, 3-
(2,6-dibromophenyl) -5- (4-isopropoxycarbonylphenyl) -1-methyl-1H-1,
2,4-triazole, 3- (2,6-difluorophenyl) -5- (4-methoxycarbonylphenyl) -1
-Ethyl-1H-1,2,4-triazole, 3-
(2,6-Dichlorophenyl) -5- (4-cyclohexyloxycarbonylphenyl) -1-methyl-1H-
1,2,4-triazole, 3- (2,6-dibromophenyl) -5- (4-butoxycarbonylphenyl)-
1-methyl-1H-1,2,4-triazole, 3-
(2,6-Difluorophenyl) -5- (4-methoxycarbonylphenyl) -1-butyl-1H-1,2,4
-Triazole, 3- (2-bromo-6-chlorophenyl) -5- (4-methoxycarbonylphenyl) -1-
Examples thereof include cyclohexyl-1H-1,2,4-triazole.
【００４０】[0040]
【発明の効果】本発明により修飾汎用性が高く殺虫、殺
ダニ剤の製造に重要な中間体であるヒドロキシメチルト
リアゾール誘導体を簡便に収率よく得る方法が提供さ
れ、殺虫、殺ダニ剤として有用な種々のフェニルトリア
ゾール誘導体を従来よりも短い工程で、工業的に製造す
る事が可能となった。さらには本発明方法において重要
な中間体でもある文献未記載の新規化合物アルコキシカ
ルボニルフェニルトリアゾール誘導体が提供される。INDUSTRIAL APPLICABILITY The present invention provides a method for easily obtaining a hydroxymethyltriazole derivative, which is an important intermediate for the production of insecticides and acaricides, in a high yield, and is useful as an insecticide or acaricide. It has become possible to industrially manufacture various phenyltriazole derivatives in a step shorter than ever before. Furthermore, a novel compound alkoxycarbonylphenyltriazole derivative, which has not been described in the literature, is also provided which is an important intermediate in the method of the present invention.
【００４１】[0041]
【実施例】以下、実施例により本発明をさらに具体的に
説明する。EXAMPLES The present invention will be described in more detail below with reference to examples.
【００４２】実施例１ 〔３−（２−クロロ−６−フルオロフェニル）−５−
（４−メトキシカルボニルフェニル）−１−メチル−１
Ｈ−１，２，４−トリアゾールの製造〕温度計、還流コ
ンデンサー、攪拌機を備えた１００ｍｌ反応フラスコに
クロロベンゼン２０ｍｌ、４−シアノ安息香酸メチル
８．２ｇ（０．０５１モル）、塩化第二鉄８．３ｇ
（０．０５１モル）を加え、攪拌しながら１２０℃に昇
温した。Ｎ−メチル−Ｎ−メタンスルホニル−２−クロ
ロ−６−フルオロベンゾヒドラゾノイルクロリド１５．
１ｇ（０．０５モル）をクロロベンゼン２０ｍｌに溶解
した溶液を１２０℃で攪拌下、滴下ロートより加えた。
更に６〜８時間反応し、反応を終了した。反応液を水１
００ｍｌにあけ、クロロホルム５０ｍｌで抽出した。有
機層を分液し、これを水洗、乾燥、濃縮したのちイソプ
ロピルアルコールで再結晶により精製して、淡褐色結晶
の３−（２−クロロ−６−フルオロフェニル）−５−
（４−メトキシカルボニルフェニル）−５−メチル−１
Ｈ−１，２，４−トリアゾールを１０．５ｇ得た（収率
６０．９％）。液体クロマトグラフィーで分析したとこ
ろ純度は９９．６％であった。Example 1 [3- (2-chloro-6-fluorophenyl) -5-
(4-Methoxycarbonylphenyl) -1-methyl-1
Production of H-1,2,4-triazole] In a 100 ml reaction flask equipped with a thermometer, a reflux condenser and a stirrer, 20 ml of chlorobenzene, 8.2 g (0.051 mol) of methyl 4-cyanobenzoate, and ferric chloride 8 were added. 0.3 g
(0.051 mol) was added, and the temperature was raised to 120 ° C. with stirring. N-methyl-N-methanesulfonyl-2-chloro-6-fluorobenzohydrazonoyl chloride 15.
A solution prepared by dissolving 1 g (0.05 mol) in 20 ml of chlorobenzene was added at 120 ° C. with stirring from a dropping funnel.
The reaction was further continued for 6 to 8 hours to complete the reaction. The reaction solution is water 1
The mixture was poured into 00 ml and extracted with 50 ml of chloroform. The organic layer was separated, washed with water, dried and concentrated, and then purified by recrystallization with isopropyl alcohol to give 3- (2-chloro-6-fluorophenyl) -5- as light brown crystals.
(4-Methoxycarbonylphenyl) -5-methyl-1
10.5 g of H-1,2,4-triazole was obtained (yield 60.9%). When analyzed by liquid chromatography, the purity was 99.6%.
【００４３】融点：１１６〜１１８．５℃1 Ｈ−ＮＭＲ（ＣＤＣｌ 3）：３．９４（ｓ，３Ｈ）、
４．１０（ｓ，３Ｈ）、７．１３〜８．２８（ｍ，７
Ｈ） ＩＲ（ｎｅａｔ）：２９３０、１７１８、１７４２、１
２７０、１１０５、８９５ｃｍ-1 Melting point: 116 to 118.5 ° C.1 H-NMR (CDCl 3): 3.94 (s, 3H),
4.10 (s, 3H), 7.13 to 8.28 (m, 7)
H) IR (neat): 2930, 1718, 1742, 1
270, 1105, 895 cm-1
【００４４】〔３−（２−クロロ−６−フルオロフェニ
ル）−５−（４−ヒドロキシメチルフェニル）−１−メ
チル−１Ｈ−１，２，４−トリアゾールの製造〕温度
計、還流コンデンサー、攪拌機を備えた３００ｍｌ容の
反応フラスコにブタノール１２０ｍｌと前記と同様にし
て得た３−（２−クロロ−６−フルオロフェニル）−５
−（４−メトキシカルボニルフェニル）−１−メチル−
１Ｈ−１，２，４−トリアゾール３４．６ｇ（０．１モ
ル）を加え、攪拌しながら５０℃に昇温し、水素化ホウ
素ナトリウム１１．３４ｇ（０．３モル）を３回に分け
て加えた。そのまま２４時間攪拌したのち反応液に水２
００ｍｌ、トルエン５０ｍｌを加え塩酸で中和した。有
機層を水洗、乾燥、濃縮し、類白色結晶の３−（２−ク
ロロ−６−フルオロフェニル）−５−（４−ヒドロキシ
メチルフェニル）−１−メチル−１Ｈ−１，２，４−ト
リアゾールを３１．０ｇ得た（収率９７．４％）。純度
は９６．４％であった。[Production of 3- (2-chloro-6-fluorophenyl) -5- (4-hydroxymethylphenyl) -1-methyl-1H-1,2,4-triazole] Thermometer, reflux condenser, stirrer 120 ml of butanol and 3- (2-chloro-6-fluorophenyl) -5 obtained in the same manner as above in a 300 ml reaction flask equipped with
-(4-Methoxycarbonylphenyl) -1-methyl-
34.6 g (0.1 mol) of 1H-1,2,4-triazole was added, the temperature was raised to 50 ° C. with stirring, and 11.34 g (0.3 mol) of sodium borohydride was divided into 3 portions. added. After stirring for 24 hours as it is, water 2 is added to the reaction solution.
00 ml and 50 ml of toluene were added and neutralized with hydrochloric acid. The organic layer was washed with water, dried and concentrated to give white crystals of 3- (2-chloro-6-fluorophenyl) -5- (4-hydroxymethylphenyl) -1-methyl-1H-1,2,4-triazole. Was obtained (yield 97.4%). The purity was 96.4%.
【００４５】融点：１３３．５〜１３５．５℃1 Ｈ−ＮＭＲ（ＣＤＣｌ 3）：２．６１（Ｔ，１Ｈ）、
４．０７（ｓ，３Ｈ）、４．７７（Ｄ，２Ｈ）７．１３
〜８．２８（ｍ，７Ｈ） ＩＲ（ｎｅａｔ）：３２７５、１４５８、１４３８、１
３４０、１０４５、８８５ｃｍ-1 Melting point: 133.5 to 135.5 ° C.1 H-NMR (CDCl 3): 2.61 (T, 1H),
4.07 (s, 3H), 4.77 (D, 2H) 7.13
~ 8.28 (m, 7H) IR (neat): 3275, 1458, 1438, 1
340, 1045, 885 cm-1
【００４６】参考例１〜２ 実施例１で用いた塩化第二鉄に代えて下記（表１）記載
のルイス酸０．０５１モルを用いた以外は実施例１と同
様の操作を行い３−（２−クロロ−６−フルオロフェニ
ル）−５−（４−メトキシカルボニルフェニル）−１−
メチル−１Ｈ−１，２，４−トリアゾールの製造を行っ
た。その結果を（表１）に示す。Reference Examples 1 and 2 The same operation as in Example 1 was carried out except that 0.051 mol of the Lewis acid shown in the following (Table 1) was used in place of the ferric chloride used in Example 1. (2-Chloro-6-fluorophenyl) -5- (4-methoxycarbonylphenyl) -1-
Methyl-1H-1,2,4-triazole was produced. The results are shown in (Table 1).
【００４７】[0047]
【表１】 [Table 1]
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成６年１０月２７日[Submission date] October 27, 1994
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】発明の名称[Name of item to be amended] Title of invention
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【発明の名称】 トリアゾール誘導体の製造方
法およびその中間体Title: Method for producing triazole derivative and intermediate thereof
Claims (3)
Ｒ1、Ｒ3は各々独立に低級アルキル基を示す。）で表わ
されるヒドラゾン誘導体と一般式 【化２】 （式中、Ｒ2は低級アルキル基を示す。）で表されるシ
アノ安息香酸エステルとを塩化第二鉄の存在下で反応さ
せて一般式 【化３】 （式中、Ｘ、Ｙ、Ｒ1およびＲ2は前記と同じ意味を示
す。）で表されるアルコキシカルボニルフェニルトリア
ゾール誘導体を得た後、さらにこれを還元することを特
徴とする、一般式 【化４】 （式中、Ｘ、ＹおよびＲ1は前記と同じ意味を示す。）
で表されるヒドロキシメチルフェニルトリアゾール誘導
体を製造する方法。1. A general formula: (In the formula, X and Y each independently represent a halogen atom,
R 1 and R 3 each independently represent a lower alkyl group. ) And a general formula: (Wherein R 2 represents a lower alkyl group) is reacted with a cyanobenzoate ester in the presence of ferric chloride to give a compound represented by the general formula: (Wherein X, Y, R 1 and R 2 have the same meanings as described above), and the alkoxycarbonylphenyltriazole derivative represented by the formula is further reduced. Chemical 4] (In the formula, X, Y and R 1 have the same meanings as described above.)
A method for producing a hydroxymethylphenyltriazole derivative represented by:
トリアゾール誘導体。2. A triazole derivative represented by the general formula (formula 3) according to claim 1.
Ｒ1、Ｒ3は各々独立に低級アルキル基を示す。）で表わ
されるヒドラゾン誘導体と一般式 【化６】 （式中、Ｒ2は低級アルキル基を示す。）で表されるシ
アノ安息香酸エステルとを塩化第二鉄の存在下で反応さ
せることを特徴とする一般式 【化７】 （式中、Ｘ、Ｙ、Ｒ1およびＲ2は前記と同じ意味を示
す。）で表されるアルコキシカルボニルフェニルトリア
ゾール誘導体の製造方法。3. A general formula: (In the formula, X and Y each independently represent a halogen atom,
R 1 and R 3 each independently represent a lower alkyl group. ) And a general formula: (Wherein R 2 represents a lower alkyl group) is reacted with a cyanobenzoic acid ester in the presence of ferric chloride. (In the formula, X, Y, R 1 and R 2 have the same meanings as described above.) A method for producing an alkoxycarbonylphenyltriazole derivative represented by the formula.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16742394A JP3407088B2 (en) | 1994-06-27 | 1994-06-27 | Method for producing triazole derivative and intermediate thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16742394A JP3407088B2 (en) | 1994-06-27 | 1994-06-27 | Method for producing triazole derivative and intermediate thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0812657A true JPH0812657A (en) | 1996-01-16 |
| JP3407088B2 JP3407088B2 (en) | 2003-05-19 |
Family
ID=15849431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16742394A Expired - Fee Related JP3407088B2 (en) | 1994-06-27 | 1994-06-27 | Method for producing triazole derivative and intermediate thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3407088B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015826A (en) * | 1997-04-24 | 2000-01-18 | Pechacek; James T. | 3-(substituted phenyl)-5-(thienyl or furyl)-1, 2, 4-triazole compounds |
| JP2002528450A (en) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | Process for producing 3- (substituted phenyl) -5-thienyl or furyl) -1,2,4-triazole and novel intermediate used therein |
| JP2002528449A (en) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | 3- (Substituted phenyl) -5-thienyl-1,2,4-triazole compounds having activity against whitefly |
| WO2005097759A1 (en) * | 2004-03-29 | 2005-10-20 | Merck & Co., Inc. | Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1 |
-
1994
- 1994-06-27 JP JP16742394A patent/JP3407088B2/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6015826A (en) * | 1997-04-24 | 2000-01-18 | Pechacek; James T. | 3-(substituted phenyl)-5-(thienyl or furyl)-1, 2, 4-triazole compounds |
| US6262305B1 (en) | 1997-04-24 | 2001-07-17 | Dow Agrosciences Llc | Process and intermediates for preparing 3-(substituted phenyl)-5-(thienyl or furyl)-1,2,4-triazole compounds |
| JP2002528450A (en) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | Process for producing 3- (substituted phenyl) -5-thienyl or furyl) -1,2,4-triazole and novel intermediate used therein |
| JP2002528449A (en) * | 1998-10-23 | 2002-09-03 | ダウ・アグロサイエンス・エル・エル・シー | 3- (Substituted phenyl) -5-thienyl-1,2,4-triazole compounds having activity against whitefly |
| WO2005097759A1 (en) * | 2004-03-29 | 2005-10-20 | Merck & Co., Inc. | Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1 |
| US8178546B2 (en) | 2004-03-29 | 2012-05-15 | Merck Sharp & Dohme Corp. | Diaryltriazoles as inhibitors of 11-beta-hydroxysteroid dehydrogenase-1 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3407088B2 (en) | 2003-05-19 |
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