JP3527255B2 - 6-N-substituted aminopicolinic acid derivatives and their production - Google Patents
6-N-substituted aminopicolinic acid derivatives and their productionInfo
- Publication number
- JP3527255B2 JP3527255B2 JP08754292A JP8754292A JP3527255B2 JP 3527255 B2 JP3527255 B2 JP 3527255B2 JP 08754292 A JP08754292 A JP 08754292A JP 8754292 A JP8754292 A JP 8754292A JP 3527255 B2 JP3527255 B2 JP 3527255B2
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- Japan
- Prior art keywords
- group
- general formula
- substituted
- acid derivative
- methyl
- Prior art date
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Classifications
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は除草剤として有用な６−
Ｎ，Ｎ−置換アミノ−３−〔（４，６−ジメトキシピリ
ミジン）−２−イル〕オキシピコリン酸誘導体の中間体
である６−Ｎ−置換アミノピコリン酸誘導体又は６−ア
ミノピコリン酸誘導体及びその製造法に関するものであ
る。FIELD OF THE INVENTION The present invention is useful as a herbicide.
6- N- substituted aminopicolinic acid derivative or 6-a, which is an intermediate of N, N-substituted amino-3-[(4,6-dimethoxypyrimidin) -2-yl] oxypicolinic acid derivative
The present invention relates to a minocicolinic acid derivative and a method for producing the same.
【０００２】[0002]
【従来技術】これまで、６−Ｎ，Ｎ−置換アミノ−３−
ピリミジン−２−イルオキシピコリン酸誘導体が除草活
性を有することが知られている（例えば特開平３−１０
６８７６号明細書）。しかし、具体的な化合物は記載さ
れていなく、記載された化合物の除草活性も好ましいも
のではない。2. Description of the Prior Art Up to now, 6-N, N-substituted amino-3-
It is known that a pyrimidin-2-yloxypicolinic acid derivative has herbicidal activity (for example, JP-A-3-10).
6876). However, no specific compound is described, and the herbicidal activity of the described compound is not preferable.
【０００３】[0003]
【発明が解決しようとする課題】本発明者らは６−Ｎ，
Ｎ−置換アミノ−３−〔（４，６−ジメトキシピリミジ
ン−２−イル〕オキシピコリン酸誘導体が極めて優れた
除草活性を有することを見出した（特願平２−２８８１
８０号明細書）。これらの化合物の中で、例えば６−
Ｎ，Ｎ−ジメチルアミノ−３−〔（４，６−ジメトキシ
ピリミジン−２−イル〕オキシピコリン酸メチルは４，
６−ジメトキシ−２−メチルスルホニルピリミジンと３
−ヒドロキシ−６−（Ｎ，Ｎ−ジメチルアミノ）ピコリ
ン酸メチルとを反応させて製造することができる。DISCLOSURE OF THE INVENTION The present inventors have proposed 6-N,
It was found that an N-substituted amino-3-[(4,6-dimethoxypyrimidin-2-yl] oxypicolinic acid derivative has extremely excellent herbicidal activity (Japanese Patent Application No. 2881/1990).
No. 80). Among these compounds, for example, 6-
Methyl N, N-dimethylamino-3-[(4,6-dimethoxypyrimidin-2-yl] oxypicolinate is 4,
6-dimethoxy-2-methylsulfonylpyrimidine and 3
It can be produced by reacting with methyl-hydroxy-6- (N, N-dimethylamino) picolinate.
【０００４】しかしながら、この反応の原料として用い
る６−Ｎ−置換アミノピコリン酸誘導体の入手は難し
く、しかも本誘導体を得る方法も本発明者らが見出した
方法（上記明細書記載）以外にいまだ開発されていな
い。However, it is difficult to obtain a 6- N- substituted aminopicolinic acid derivative used as a starting material for this reaction, and a method for obtaining this derivative is still developed other than the method found by the present inventors (described in the above specification). It has not been.
【０００５】一般にピリジンＮ−オキシドとフェニルイ
ソシアナートとを反応させてピリジンの２位にアニリノ
基を導入する方法〔ケミカル・アンド・ファーマシュー
ティカル・ビュレチン（Ｃｈｅｍ．Ｐｈａｒｍ．Ｂｕ１
１．）２２巻（７）１６１１〜１６１７頁（１９７４
年）〕等が知られているが、本発明に使用する一般式
（ＩＩ）で示される３−ヒドロキシピコリン酸Ｎ−オキ
シドへの適応は困難である。また４，６−ジメトキシ−
２−メチルスルホニルピリミジンと３−ヒドロキシ−６
−（Ｎ，Ｎ−ジメチルアミノ）ピコリン酸メチルとを反
応させる方法は反応試薬から不可避的に目的としない副
生成物が相当量得られること、及び室温下で反応完結に
長時間を要すること等、数多くの改善の余地がある。従
って、６−Ｎ−置換アミノピコリン酸誘導体の製造法の
開発が望まれている。Generally, a method of reacting pyridine N-oxide with phenyl isocyanate to introduce an anilino group at the 2-position of pyridine [Chemical and Pharmaceutical Buretin (Chem. Pharm. Bu1
1. ) 22 (7) 1611-1617 (1974
, Etc.) are known, but it is difficult to apply them to 3-hydroxypicolinic acid N-oxide represented by the general formula (II) used in the present invention. In addition, 4,6-dimethoxy-
2-Methylsulfonylpyrimidine and 3-hydroxy-6
The method of reacting with methyl- (N, N-dimethylamino) picolinate is that a considerable amount of undesired by-product is unavoidably obtained from the reaction reagent, and that it takes a long time to complete the reaction at room temperature. , There is plenty of room for improvement. Therefore, development of a method for producing a 6- N- substituted aminopicolinic acid derivative is desired.
【０００６】本発明者らは、このような６−Ｎ−置換ア
ミノピコリン酸誘導体の製造方法の欠点を克服するため
鋭意研究を重ねた結果、一般式（ＩＩ）で示されるピコ
リン酸Ｎ−オキシド誘導体と所望のアミンから得られる
カルバモイル化合物とを反応させることにより、ピコリ
ン酸の６位に所望のアミノ基が導入されたピコリン酸誘
導体が得られることを見い出し本発明を完成した。The present inventors have conducted extensive studies in order to overcome the drawbacks of such a method for producing a 6-N-substituted aminopicolinic acid derivative, and as a result, the picolinic acid N-oxide represented by the general formula (II) has been obtained. It was found that a picolinic acid derivative having a desired amino group introduced at the 6-position of picolinic acid can be obtained by reacting the derivative with a carbamoyl compound obtained from the desired amine, and completed the present invention.
【０００７】[0007]
【課題を解決するための手段】すなわち、本発明の６−
Ｎ−置換アミノピコリン酸誘導体又は６−アミノピコリ
ン酸誘導体は一般式（Ｉ）[Means for Solving the Problems] That is, 6-of the present invention
N-Substituted aminopicolinic acid derivative or 6-aminopicolin
The acid derivative has the general formula (I)
【０００８】[0008]
【化４】 [Chemical 4]
【０００９】（式中、Ｒ１，Ｒ２は同一又は相異なり、
水素原子、アルキル基、ハロゲン原子、アルコキシアル
キル基、シアノアルキル基、シクロアルキル基、アルコ
キシ基、アルコキシカルボニルアルキル基、アシル基、
アルケニル基、アルキニル基、ベンジル基又はフェニル
基を示し、Ｒ１とＲ２は相隣る窒素原子とともに３〜９
員のヘテロ環を形成することもでき、このヘテロ環には
酸素原子、硫黄原子又は基＞Ｎ−Ｒ５を含んでもよい。
Ｒ３は水素原子、低級アルキル基又はベンジル基を示
し、Ｒ４は水素原子又は水酸基の保護基を示し、Ｒ５は
低級アルキル基、ベンジル基又はアシル基を示す。）で
表される。(Wherein R 1 and R 2 are the same or different,
Hydrogen atom, alkyl group, halogen atom, alkoxyalkyl group, cyanoalkyl group, cycloalkyl group, alkoxy group, alkoxycarbonylalkyl group, acyl group,
An alkenyl group, an alkynyl group, a benzyl group or a phenyl group is shown, and R 1 and R 2 are 3 to 9 together with adjacent nitrogen atoms.
Membered heterocycle may be formed, and the heterocycle may contain an oxygen atom, a sulfur atom or a group> N—R 5 .
R 3 represents a hydrogen atom, a lower alkyl group or a benzyl group, R 4 represents a hydrogen atom or a protective group for a hydroxyl group, and R 5 represents a lower alkyl group, a benzyl group or an acyl group. ).
【００１０】また、これらの６−Ｎ−置換アミノピコリ
ン酸誘導体又は６−アミノピコリン酸誘導体の製造法は
一般式（ＩＩ）Further, the method for producing these 6-N-substituted aminopicolinic acid derivatives or 6-aminopicolinic acid derivatives is represented by the general formula (II)
【００１１】[0011]
【化５】 [Chemical 5]
【００１２】（式中、Ｒ３，Ｒ４は上記と同じ意味を示
す。）で表されるピコリン酸Ｎ−オキシド誘導体と一般
式（ＩＩＩ）(Wherein R 3 and R 4 have the same meanings as described above) and a picolinic acid N-oxide derivative represented by the general formula (III)
【００１３】[0013]
【化６】 [Chemical 6]
【００１４】（式中、Ｒ１及びＲ２は上記と同じ意味を
示し、Ｌは脱離基を示す。）で表されるカルバモイルク
ロリドとを反応させてなる。次に反応式によって示す。(In the formula, R 1 and R 2 have the same meanings as described above, and L represents a leaving group), and the reaction is carried out with a carbamoyl chloride. The reaction formula is shown below.
【００１５】[0015]
【化７】 [Chemical 7]
【００１６】（式中、Ｒ１，Ｒ２、Ｒ３、Ｒ４及びＬは
前記と同じ意味を示す。）すなわち、一般式（Ｉ）で表
される化合物は一般式（ＩＩ）で表される化合物と一般
式（ＩＩＩ）で表される化合物とを不活性溶媒中で０℃
から溶媒の沸点の温度範囲で反応させることにより得る
ことができる。溶媒としては、例えばトルエン、ベンゼ
ン、キシレン等の炭化水素系溶媒、塩化メチレン、クロ
ロホルム等のハロゲン化炭化水素系溶媒、エチルエーテ
ル、イソプロピルエーテル、テトラヒドロフラン、１，
４−ジオキサン等のエーテル系溶媒、Ｎ，Ｎ−ジメチル
ホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、ジメチ
ルスルホキシド等の非プロトン性極性溶媒、酢酸エチル
等のエステル系溶媒やアセトニトリル等が使用できる。
好ましくはアセトニトリル、テトラヒドロフラン等が挙
げられる。溶媒の使用量は一般式（ＩＩ）で示される化
合物１モルに対して０．０１〜１０リットル、好ましく
は１．０〜５．０リットルの範囲である。また、好まし
い条件としてはアセトニトリル中での還流が挙げられ
る。一般式（ＩＩ）で表される化合物に対して、一般式
（ＩＩＩ）で表される化合物は等量又はそれ以上の量を
用いてもさしつかえない。(In the formula, R 1 , R 2 , R 3 , R 4 and L have the same meanings as described above.) That is, the compound represented by the general formula (I) is represented by the general formula (II). And a compound represented by the general formula (III) at 0 ° C. in an inert solvent.
To the boiling point of the solvent. Examples of the solvent include hydrocarbon solvents such as toluene, benzene and xylene, halogenated hydrocarbon solvents such as methylene chloride and chloroform, ethyl ether, isopropyl ether, tetrahydrofuran, 1,
An ether solvent such as 4-dioxane, an aprotic polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide and dimethylsulfoxide, an ester solvent such as ethyl acetate and acetonitrile can be used.
Preferred are acetonitrile, tetrahydrofuran and the like. The amount of solvent used is in the range of 0.01 to 10 liters, preferably 1.0 to 5.0 liters, relative to 1 mol of the compound represented by the general formula (II). Further, a preferable condition is reflux in acetonitrile. The compound represented by the general formula (III) may be used in an equal amount or more than the compound represented by the general formula (II).
【００１７】本反応においては塩基を加えなくても反応
は進行するが好ましくは加えた方が良い。塩基として
は、例えばアルカリ金属又はアルカリ土類金属、特にナ
トリウム及びカリウム並びにマグネシウム及びカルシウ
ムの炭酸塩、炭酸水素塩、酢酸塩、アルコラート、水酸
化合物又は酸化物等が使用できる。更に有機塩基、例え
ばピリジン、トリエチルアミン、Ｎ，Ｎ−ジイソプロピ
ルエチルアミン等の３級アミンをも使用することが出来
る。好ましくはＮ，Ｎ−ジイソプロピルエチルアミン等
が挙げられる。塩基の使用量は一般式（ＩＩＩ） で示
される化合物に対して等モル以上が好ましいが、特定さ
れない。脱離基としては、塩素原子等のハロゲン原子、
アルコキシ基、イミダゾール等を使用することができ
る。好ましくは塩素原子が挙げられる。脱離基が塩素原
子の場合は所望により、ヨウ化カリウムやヨウ化ナトリ
ウム等を一般式（ＩＩＩ）で示される化合物に対し、触
媒量から等モル以上加えることにより、一般式（ＩＩ
Ｉ）で示される化合物の反応性を高めることができる。In this reaction, the reaction proceeds without adding a base, but it is preferable to add it. As the base, for example, alkali metal or alkaline earth metal, particularly sodium and potassium and magnesium and calcium carbonates, hydrogen carbonates, acetates, alcoholates, hydroxide compounds or oxides and the like can be used. Furthermore, organic bases, for example, tertiary amines such as pyridine, triethylamine and N, N-diisopropylethylamine can be used. Preferred examples include N, N-diisopropylethylamine. The amount of the base used is preferably equimolar or more to the compound represented by the general formula (III), but is not specified. As the leaving group, a halogen atom such as chlorine atom,
An alkoxy group, imidazole, etc. can be used. A chlorine atom is preferable. When the leaving group is a chlorine atom, if desired, potassium iodide, sodium iodide, or the like is added to the compound represented by the general formula (III) in a molar amount from the catalytic amount to give a compound represented by the general formula (II).
The reactivity of the compound represented by I) can be increased.
【００１８】このようにして得られる一般式（Ｉ）で示
される６−Ｎ−置換アミノピコリン酸誘導体又は６−ア
ミノピコリン酸誘導体は有用な中間体であり下記のスキ
ームに従い種々の有用な化合物に導くことができる。The thus obtained 6- N- substituted aminopicolinic acid derivative represented by the general formula (I) or 6-a
Minopolinic acid derivatives are useful intermediates and can be led to various useful compounds according to the following schemes.
【００１９】[0019]
【化８】 [Chemical 8]
【００２０】（式中、Ｒ１，Ｒ２、Ｒ３及びＲ４は前記
と同じ意味を示す。）すなわち、Ｒ４が水酸基の保護基
の場合には、保護基を脱離して一般式（ＩＶ）で示され
る化合物を製造したのち，４，６−ジメトキシ−２−メ
チルスルホニルピリミジンを塩基の存在下に反応させて
一般式（Ｖ）で示される化合物を得ることができる。一
般式（Ｖ）で示される化合物のうち、Ｒ１，Ｒ２のいず
れか又は双方がベンジル基に代表されるアミノ基の保護
基の場合には、更に順を追って脱離させることにより一
般式（ＶＩ）で示される６−モノ置換アミノ体、そして
一般式（ＶＩＩ） で示される６−アミノ体を得ること
ができる。Ｒ１又はＲ２がベンジル基の場合は接触水素
添加による脱離が可能であるが、これに特定されるもの
ではない。(In the formula, R 1 , R 2 , R 3 and R 4 have the same meanings as described above.) That is, when R 4 is a hydroxyl-protecting group, the protecting group is eliminated to give the general formula ( After producing the compound represented by IV), 4,6-dimethoxy-2-methylsulfonylpyrimidine can be reacted in the presence of a base to obtain the compound represented by the general formula (V). In the compound represented by the general formula (V), when either or both of R 1 and R 2 are a protecting group for an amino group represented by a benzyl group, the compound represented by the general formula (V) A 6-mono-substituted amino compound represented by (VI) and a 6-amino compound represented by the general formula (VII) can be obtained. When R 1 or R 2 is a benzyl group, elimination by catalytic hydrogenation is possible, but it is not limited to this.
【００２１】一方、一般式（Ｉ）で示される化合物のＲ
１，Ｒ２のいずれか又は双方を同様の方法で脱離させる
ことにより一般式（ＶＩＩＩ）又は（Ｘ）で示される化
合物を得て、更にそれぞれのもつＲ４を脱離させること
によって一般式（ＩＸ）又は（ＸＩ）で示される化合物
を得たのち、４，６−ジメトキシ−２−メチルスルホニ
ルピリミジンを塩基の存在下に反応させてそれぞれ一般
式（ＶＩ）又は（ＶＩＩ）で示される化合物を得ること
もできる。On the other hand, R of the compound represented by the general formula (I)
1 or R 2 is eliminated by a similar method to obtain a compound represented by the general formula (VIII) or (X), and further R 4 is removed to eliminate the general formula After obtaining the compound represented by (IX) or (XI), 4,6-dimethoxy-2-methylsulfonylpyrimidine is reacted in the presence of a base to give a compound represented by the general formula (VI) or (VII), respectively. You can also get
【００２２】次に、一般式（Ｉ）及び（Ｖ）で示される
６−Ｎ−置換アミノピコリン酸誘導体又は６−アミノピ
コリン酸誘導体の具体例を表１〜９に示すが、本発明は
これらに限られるものではない。なお、表中のＰｈはフ
ェニル基を示す。表５〜９に記載の化合物には、すぐれ
た除草活性並びに殺菌活性を有するものが多い。Next, a 6- N- substituted aminopicolinic acid derivative represented by the general formulas (I) and (V) or 6-aminopycolic acid
Specific examples of the choline derivative are shown in Tables 1 to 9, but the present invention is not limited to these. In addition, Ph in the table represents a phenyl group. The compounds listed in Table 5-9, many of them have excellent herbicidal activity and disinfecting activity.
【００２３】[0023]
【表１】 [Table 1]
【００２４】[0024]
【表２】 [Table 2]
【００２５】[0025]
【表３】 [Table 3]
【００２６】[0026]
【表４】 [Table 4]
【００２７】[0027]
【表５】 [Table 5]
【００２８】[0028]
【表６】 [Table 6]
【００２９】[0029]
【表７】 [Table 7]
【００３０】[0030]
【表８】 [Table 8]
【００３１】[0031]
【表９】 [Table 9]
【００３２】[0032]
【実施例】次に実施例を挙げて本発明を具体的に説明す
る。EXAMPLES Next, the present invention will be specifically described with reference to examples.
【００３３】実施例１ ６−（Ｎ−ベンジル−Ｎ−メチ
ルアミノ）−３−ベンジルオキシピコリン酸メチルの合
成（化合物２０）
３−ベンジルオキシピコリン酸メチル−Ｎ−オキシド
６．４８ｇ（０．０２５モル）、Ｎ−ベンジル−Ｎ−メ
チルカルバモイルクロリド９．１８ｇ（０．０５モ
ル）、Ｎ，Ｎ−ジイソプロピルエチルアミン６．４６ｇ
（０．０５モル）及びヨウ化ナトリウム７．４９ｇ
（０．０５モル）をアセトニトリル１５０ｍｌ中にて２
時間加熱還流した。その後、水を加え、エーテル抽出
し、飽和食塩水にて洗浄し、炭酸カリウムにて乾燥し
た。溶媒を留去し、得られた混合物をカラムクロマトグ
ラフィー（シリカゲル、酢酸エチル−ｎ−ヘキサン
（１：６））にて分離、精製した。主たる溶出液を濃縮
し６−（Ｎ−ベンジル−Ｎ−メチルアミノ）−３−ベン
ジルオキシピコリン酸メチル４．１０ｇを油状物として
得た。（収率４５．２％）Example 1 Synthesis of methyl 6- (N-benzyl-N-methylamino) -3-benzyloxypicolinate (Compound 20) 6.48 g (0.025) of methyl 3-benzyloxypicolinate-N-oxide Mol), N-benzyl-N-methylcarbamoyl chloride 9.18 g (0.05 mol), N, N-diisopropylethylamine 6.46 g
(0.05 mol) and sodium iodide 7.49 g
2 (0.05 mol) in 150 ml of acetonitrile
Heated to reflux for hours. Then, water was added, the mixture was extracted with ether, washed with saturated brine, and dried with potassium carbonate. The solvent was evaporated, and the obtained mixture was separated and purified by column chromatography (silica gel, ethyl acetate-n-hexane (1: 6)). The main eluate was concentrated to obtain 4.10 g of methyl 6- (N-benzyl-N-methylamino) -3-benzyloxypicolinate as an oil. (Yield 45.2%)
【００３４】実施例２ ６−（Ｎ−ベンジル−Ｎ−メチ
ルアミノ）−３−ヒドロキシピコリン酸メチルの合成
（化合物１９）
６−（Ｎ−ベンジル−Ｎ−メチルアミノ）−３−ベンジ
ルオキシピコリン酸メチル４．１５ｇ（０．０１５モ
ル）を１０％パラジウム炭素０．８ｇの存在下、メタノ
ール１８０ｍｌ中にて水素添加した。触媒を除去した
後、溶媒を留去し、得られた混合物をカラムクロマトグ
ラフィー（シリカゲル、酢酸エチル−ｎ−ヘキサン
（１：４））にて分離、精製した。主たる溶出液を濃縮
し６−（Ｎ−ベンジル−Ｎ−メチルアミノ）−３−ヒド
ロキシピコリン酸メチル１．６１ｇを油状物として得
た。（収率５１．６％）Example 2 Synthesis of methyl 6- (N-benzyl-N-methylamino) -3-hydroxypicolinate (Compound 19) 6- (N-benzyl-N-methylamino) -3-benzyloxypicolinic acid 4.15 g (0.015 mol) of methyl was hydrogenated in 180 ml of methanol in the presence of 0.8 g of 10% palladium on carbon. After removing the catalyst, the solvent was distilled off, and the obtained mixture was separated and purified by column chromatography (silica gel, ethyl acetate-n-hexane (1: 4)). The main eluate was concentrated to obtain 1.61 g of methyl 6- (N-benzyl-N-methylamino) -3-hydroxypicolinate as an oil. (Yield 51.6%)
【００３５】実施例３ ３−ベンジルオキシ−６−（１
−ピロリジニル）ピコリン酸メチルの合成（化合物８）
３−ベンジルオキシピコリン酸メチル−Ｎ−オキシド
６．４８ｇ（０．０２５モル）、１−ピロリジンカルボ
ニルクロリド６．６８ｇ（０．０５モル）、Ｎ，Ｎ−ジ
イソプロピルエチルアミン６．４６ｇ（０．０５モル）
及びヨウ化ナトリウム７．４９ｇ（０．０５モル）をア
セトニトリル２００ｍｌ中にて加熱還流した。溶媒を留
去し、水を加え酢酸エチルにて抽出し、飽和食塩水にて
洗浄後、硫酸マグネシウムにて乾燥した。溶媒を留去
後、得られた混合物をカラムクロマトグラフィー（シリ
カゲル、酢酸エチル−ｎ−ヘキサン（１：６））にて、
分離、精製した。主たる溶出液を濃縮し３−ベンジルオ
キシ−６−（１−ピロリジニル）ピコリン酸メチル（融
点１２０〜１２１．５℃）６．５０ｇを得た。（収率８
３．０％）Example 3 3-benzyloxy-6- (1
Synthesis of methyl-pyrrolidinyl) picolinate (Compound 8) 6.48 g (0.025 mol) methyl 3-benzyloxypicolinate-N-oxide, 6.68 g (0.05 mol) 1-pyrrolidinecarbonyl chloride, N, N-diisopropylethylamine 6.46 g (0.05 mol)
And 7.49 g (0.05 mol) of sodium iodide were heated to reflux in 200 ml of acetonitrile. The solvent was evaporated, water was added, the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. After distilling off the solvent, the obtained mixture was subjected to column chromatography (silica gel, ethyl acetate-n-hexane (1: 6)),
Separated and purified. The main eluate was concentrated to obtain 6.50 g of methyl 3-benzyloxy-6- (1-pyrrolidinyl) picolinate (melting point 120-121.5 ° C). (Yield 8
3.0%)
【００３６】実施例４ ３−ヒドロキシ−６−（１−ピ
ロリジニル）ピコリン酸メチルの合成（化合物７）
３−ベンジルオキシ−６−（１−ピロリジニル）ピコリ
ン酸メチル６．１０ｇ（０．０１９５モル）を１０％パ
ラジウム炭素１．５ｇの存在下、メタノール１５０ｍｌ
中水素添加した。触媒を除去し、溶媒を留去後、イソプ
ロピルエーテル−ｎ−ヘキサンにて結晶化し、３−ヒド
ロキシ−６−（１−ピロリジニル）ピコリン酸メチル
（融点８７〜９０℃）４．３３ｇを得た。 （収率１０
０％）Example 4 Synthesis of methyl 3-hydroxy-6- (1-pyrrolidinyl) picolinate (Compound 7) 6.10 g (0.0195 mol) of methyl 3-benzyloxy-6- (1-pyrrolidinyl) picolinate 150 ml of methanol in the presence of 1.5 g of 10% palladium on carbon
Medium hydrogenated. The catalyst was removed, the solvent was evaporated, and the residue was crystallized from isopropyl ether-n-hexane to obtain 4.33 g of methyl 3-hydroxy-6- (1-pyrrolidinyl) picolinate (melting point 87 to 90 ° C). (Yield 10
0%)
【００３７】次に原料化合物及び最終生成物の製造法を
参考例として挙げて説明する。
参考例１ ３−ベンジルオキシピコリン酸メチル−Ｎ−
オキシドの合成
１１ナスフラスコに、３−ベンジルオキシピコリン酸メ
チル１４７．５ｇ（０．６１モル）と酢酸４００ｍｌを
加えたのち、３５％過酸化水素７１ｇ（０．７３モル）
を添加して７０〜８０℃で６時間反応させた。反応終了
後、酢酸を減圧留去した。残渣をクロロホルムで抽出
し、炭酸水素ナトリウム水溶液、水の順で洗浄後、乾
燥、濃縮して得られる油状物に酢酸エチルを加えて結晶
化させた。収量９３ｇ（収率５９％）Next, the production methods of the raw material compound and the final product will be described as reference examples. Reference Example 1 Methyl 3-benzyloxypicolinate-N-
Synthesis of Oxide 11 To a round-bottomed flask, 147.5 g (0.61 mol) of methyl 3-benzyloxypicolinate and 400 ml of acetic acid were added, and then 71 g (0.73 mol) of 35% hydrogen peroxide was added.
Was added and reacted at 70 to 80 ° C. for 6 hours. After completion of the reaction, acetic acid was distilled off under reduced pressure. The residue was extracted with chloroform, washed with an aqueous sodium hydrogen carbonate solution and water in this order, dried and concentrated, and ethyl acetate was added to the oily substance obtained for crystallization. Yield 93g (59% yield)
【００３８】参考例２ ６−（Ｎ−ベンジル−Ｎ−メチ
ルアミノ）−３−〔（４，６−ジメトキシピリミジン−
２−イル）オキシ〕−ピコリン酸メチルの合成（化合物
７１）
６−（Ｎ−ベンジル−Ｎ−メチルアミノ）−３−ヒドロ
キシピコリン酸メチル１．６１ｇ（０．００５９モ
ル）、４，６−ジメトキシ−２−メチルスルホニルピリ
ミジン１．５４ｇ（０．００７１モル）及び炭酸ナトリ
ウム０．８１ｇ（０．００５９モル）をＮ，Ｎ−ジメチ
ルホルムアミド５０ｍｌ中１００℃にて３時間加熱攪拌
した。氷水を加え、酢酸エチルにて抽出し、飽和食塩水
にて洗浄後、硫酸マグネシウムにて乾燥した。溶媒を留
去し、得られた混合物をカラムクロマトグラフィ（シリ
カゲル、酢酸エチル−ｎ−ヘキサン（１：４））にて分
離、精製した。主たる溶出液を濃縮し６−（Ｎ−ベンジ
ル−Ｎ−メチルアミノ）−３−〔（４，６−ジメトキシ
ピリミジン−２−イル）オキシ〕ピコリン酸メチル（融
点７３〜７５℃）２．１０ｇを得た。（収率７２．２
％）Reference Example 2 6- (N-benzyl-N-methylamino) -3-[(4,6-dimethoxypyrimidine-
Synthesis of methyl 2-yl) oxy] -picolinate (Compound 71) Methyl 6- (N-benzyl-N-methylamino) -3-hydroxypicolinate 1.61 g (0.0059 mol), 4,6-dimethoxy 1.54 g (0.0071 mol) of 2-methylsulfonylpyrimidine and 0.81 g (0.0059 mol) of sodium carbonate were heated and stirred in 50 ml of N, N-dimethylformamide at 100 ° C. for 3 hours. Ice water was added, the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated, and the obtained mixture was separated and purified by column chromatography (silica gel, ethyl acetate-n-hexane (1: 4)). The main eluate was concentrated to give 2.10 g of methyl 6- (N-benzyl-N-methylamino) -3-[(4,6-dimethoxypyrimidin-2-yl) oxy] picolinate (melting point 73-75 ° C). Obtained. (Yield 72.2
%)
【００３９】参考例３ ３−〔（４，６−ジメトキシピ
リミジン−２−イル）オキシ〕−６−メチルアミノピコ
リン酸メチルの合成（化合物７３）
６−（Ｎ−ベンジル−Ｎ−メチルアミノ）−３−
〔（４，６−ジメトキシピリミジン−２−イル）オキ
シ〕ピコリン酸メチル１．２３ｇ（０．００３モル）を
１０％パラジウム炭素０．３ｇの存在下、過塩素酸２滴
を加えジメトキシエタン８０ｍｌ中にて水素添加した。
触媒を除去し、溶媒を留去後、得られた混合物をカラム
クロマトグラフィ（シリカゲル、酢酸エチル−ｎ−ヘキ
サン（１：２））にて、分離、精製した。主たる溶出液
を濃縮し３−〔（４，６−ジメトキシピリミジン−２−
イル）オキシ〕−６−メチルアミノピコリン酸メチル
（融点１３７〜１３８℃）０．７０ｇを得た。（収率７
３．０％）Reference Example 3 Synthesis of methyl 3-[(4,6-dimethoxypyrimidin-2-yl) oxy] -6-methylaminopicolinate (Compound 73) 6- (N-benzyl-N-methylamino)- 3-
[(4,6-dimethoxypyrimidin-2-yl) oxy] methyl picolinate 1.23 g (0.003 mol) was added to 2 g of perchloric acid in the presence of 0.3 g of 10% palladium-carbon in 80 ml of dimethoxyethane. Hydrogenated at.
After removing the catalyst and evaporating the solvent, the obtained mixture was separated and purified by column chromatography (silica gel, ethyl acetate-n-hexane (1: 2)). The main eluate was concentrated to give 3-[(4,6-dimethoxypyrimidine-2-
There was obtained 0.70 g of methyl (yl) oxy] -6-methylaminopicolinate (melting point: 137 to 138 ° C.). (Yield 7
3.0%)
【００４０】参考例４ ３−〔（４，６−ジメトキシピ
リミジン−２−イル）オキシ〕−６−メチルアミノピコ
リン酸の合成（化合物７４）
３−［（４，６−ジメトキシピリミジン−２−イル）オ
キシ］−６−メチルアミノピコリン酸メチル０．５５ｇ
（０．００１７モル）及び水酸化カリウム０．２８６ｇ
（０．００５１モル）をメタノール１５ｍｌ、ジメトキ
シエタン５ｍｌ及び水５ｍｌ中３時間攪拌した。水を加
え、エーテル抽出後、水層を１０％塩酸にて酸性とし
（ｐＨ４）、クロロホルムにて抽出し、硫酸マグネシウ
ムにて乾燥した。溶媒を留去後、ジエチルエーテルにて
結晶化し、３−〔（４，６−ジメトキシピリミジン−２
−イル）オキシ〕−６−メチルアミノピコリン酸０．４
１ｇを無色結晶（融点１６０〜１６２℃）として得た。
（収率７９．０％）Reference Example 4 Synthesis of 3-[(4,6-dimethoxypyrimidin-2-yl) oxy] -6-methylaminopicolinic acid (Compound 74) 3-[(4,6-Dimethoxypyrimidin-2-yl) ) Oxy] -6-methylaminopicolinate methyl 0.55 g
(0.0017 mol) and 0.286 g of potassium hydroxide
(0.0051 mol) was stirred in 15 ml of methanol, 5 ml of dimethoxyethane and 5 ml of water for 3 hours. After adding water and extracting with ether, the aqueous layer was acidified with 10% hydrochloric acid (pH 4), extracted with chloroform, and dried with magnesium sulfate. After the solvent was distilled off, it was crystallized with diethyl ether to give 3-[(4,6-dimethoxypyrimidine-2
-Yl) oxy] -6-methylaminopicolinic acid 0.4
1 g was obtained as colorless crystals (melting point 160-162 ° C.).
(Yield 79.0%)
【００４１】参考例５ ３−〔（４，６−ジメトキシピ
リミジン−２−イル）オキシ〕−６−（１−ピロリジニ
ル）ピコリン酸メチルの合成（化合物７７）
３−ヒドロキシ−６−（１−ピロリジニル）ピコリン酸
メチル１．５５ｇ（０．００７モル）、４，６−ジメト
キシ−２−メチルスルホニルピリミジン１．８３ｇ
（０．００８４モル）及び炭酸カリウム０．９６ｇ
（０．００７モル）をＮ，Ｎ−ジメチルホルムアミド５
０ｍｌ中１００℃にて３時間加熱攪拌した。氷水を加
え、酢酸エチルにて抽出し、飽和食塩水にて洗浄後、硫
酸マグネシウムにて乾燥した。溶媒留去し、イソプロピ
ルエーテルにて結晶化し、３−〔（４，６−ジメトキシ
ピリミジン−２−イル）オキシ〕−６−（１−ピロリジ
ニル）ピコリン酸メチル（融点１５１〜１５３℃）２．
１１ｇを得た。（収率８４．０％）Reference Example 5 Synthesis of methyl 3-[(4,6-dimethoxypyrimidin-2-yl) oxy] -6- (1-pyrrolidinyl) picolinate (Compound 77) 3-Hydroxy-6- (1-pyrrolidinyl) ) 1.55 g (0.007 mol) of methyl picolinate, 1.83 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine
(0.0084 mol) and 0.96 g of potassium carbonate
(0.007 mol) of N, N-dimethylformamide 5
The mixture was heated and stirred in 0 ml at 100 ° C for 3 hours. Ice water was added, the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated, and crystallized from iso-flop Ropi <br/> ether, 3 - [(4,6-dimethoxypyrimidin-2-yl) oxy] -6- (1-pyrrolidinyl) picolinate (melting point 151 to 153 ° C) 2.
11 g were obtained. (Yield 84.0%)
【００４２】参考例６ ３−〔（４，６−ジメトキシピ
リミジン−２−イル）オキシ〕−６−（１−ピロリジニ
ル）ピコリン酸の合成（化合物７８）
３−〔（４，６−ジメトキシピリミジン−２−イル）オ
キシ〕−６−（１−ピロリジニル）ピコリン酸メチル
１．４４ｇ（０．００４モル）及び水酸化カリウム０．
６７ｇ（０．０１２モル）をメタノール３０ｍｌ、ジメ
トキシエタン３０ｍｌ及び水１０ｍｌ中４０℃にて４時
間攪拌した。水を加え、１０％塩酸にて酸性とし（ｐＨ
４）、クロロホルムにて抽出し、硫酸マグネシウムにて
乾燥した。溶媒留去し、イソプロピルエーテルにて結晶
化し、３−〔（４，６−ジメトキシピリミジン−２−イ
ル）オキシ〕−６−（１−ピロリジニル）ピコリン酸
（融点１７９〜１８３℃）１．２９ｇを得た。（収率９
４．０％）Reference Example 6 Synthesis of 3-[(4,6-dimethoxypyrimidin-2-yl) oxy] -6- (1-pyrrolidinyl) picolinic acid (Compound 78) 3-[(4,6-Dimethoxypyrimidine- 2-yl) oxy] -6- (1-pyrrolidinyl) picolinate methyl 1.44 g (0.004 mol) and potassium hydroxide 0.
67 g (0.012 mol) was stirred in 30 ml of methanol, 30 ml of dimethoxyethane and 10 ml of water at 40 ° C. for 4 hours. Add water and acidify with 10% hydrochloric acid (pH
4), extracted with chloroform and dried over magnesium sulfate. The solvent was evaporated, and crystallized from iso-flop Ropirueteru, 3 - [(4,6-dimethoxypyrimidin-2-yl) oxy] -6- (1-pyrrolidinyl) picolinic acid (melting point one hundred and seventy-nine to one hundred and eighty-three ° C.) 1.29 g Got (Yield 9
4.0%)
【００４３】[0043]
【発明の効果】本発明方法によれば一般式（Ｉ）で示さ
れる６−Ｎ−置換アミノピコリン酸誘導体を副生物の生
成を抑えて効率的に合成することができる。また、これ
を中間体としてすぐれた除草及び殺菌活性を有する一般
式（Ｖ）で示される化合物等に導くことができる。According to the method of the present invention, the 6-N-substituted aminopicolinic acid derivative represented by the general formula (I) can be efficiently synthesized while suppressing the production of by-products. Further, this can be led to a compound represented by the general formula (V) having excellent herbicidal and bactericidal activity as an intermediate.
【００４４】[0044]
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 平３−106876（ＪＰ，Ａ) 特開 平６−316574（ＪＰ，Ａ) Ｔａｋｕｚｏ， ＨＩＳＡＮＯ ｅｔ ａｌ．，Ｃｈｅｍ． Ｐｈａｒｍ． Ｂｕｌｌ．，日本，1974年，Ｖｏｌ. 22， Ｎｏ．７，ｐ．1611−７ (58)調査した分野(Int.Cl.7，ＤＢ名) C07D 213/79 C07D 401/12 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)─────────────────────────────────────────────────── ─── Continuation of front page (56) Reference JP-A-3-106876 (JP, A) JP-A-6-316574 (JP, A) Takazu, HISANO et al. Chem. Pharm. Bull. , Japan, 1974, Vol. 22, No. 7, p. 1611-7 (58) Fields surveyed (Int.Cl. 7 , DB name) C07D 213/79 C07D 401/12 CA (STN) REGISTRY (STN)
Claims (2)
キル基、ハロゲン原子、アルコキシアルキル基、シアノ
アルキル基、シクロアルキル基、アルコキシ基、アルコ
キシカルボニルアルキル基、アシル基、アルケニル基、
アルキニル基、ベンジル基又はフェニル基を示し、Ｒ1
とＲ2は相隣る窒素原子とともに３〜９員のヘテロ環を
形成することもでき、このヘテロ環には酸素原子、硫黄
原子又は基＞Ｎ−Ｒ5を含んでもよい。Ｒ3は水素原子、
低級アルキル基又はベンジル基を示し、Ｒ4は水素原子
又は水酸基の保護基を示し、Ｒ5は低級アルキル基、ベ
ンジル基又はアシル基を示す。）で表される６−Ｎ−置
換アミノピコリン酸誘導体又は６−アミノピコリン酸誘
導体。1. A compound represented by the general formula (I): (In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom, an alkyl group, a halogen atom, an alkoxyalkyl group, a cyanoalkyl group, a cycloalkyl group, an alkoxy group, an alkoxycarbonylalkyl group, an acyl group, an alkenyl group,
An alkynyl group, a benzyl group or a phenyl group, R 1
And R 2 can form a 3- to 9-membered hetero ring together with the adjacent nitrogen atom, and the hetero ring may contain an oxygen atom, a sulfur atom or a group> N—R 5 . R 3 is a hydrogen atom,
A lower alkyl group or a benzyl group is shown, R 4 is a hydrogen atom or a protective group for a hydroxyl group, and R 5 is a lower alkyl group, a benzyl group or an acyl group. 6-N-substituted aminopicolinic acid derivative or 6-aminopicolinic acid derivative
Conductor .
ＩＩ） 【化３】 （式中、Ｒ1、Ｒ2、Ｒ3及びＲ4は請求項１記載と同じ意
味を示し、Ｌは脱離基を示す。）で表されるカルバモイ
ルクロリドとを反応させることを特徴とする請求項１記
載の一般式（Ｉ）で表される６−Ｎ−置換アミノピコリ
ン酸誘導体又は６−アミノピコリン酸誘導体の製造法。2. A compound represented by the general formula (II): A picolinic acid N-oxide derivative represented by the general formula (I
II) (Wherein, R 1, R 2, R 3 and R 4 have the same meaning as in claim 1 wherein, L is a leaving group.) And characterized in that Ru is reacted with carbamoyl chloride represented by The method for producing a 6-N-substituted aminopicolinic acid derivative or a 6-aminopicolinic acid derivative represented by the general formula (I) according to claim 1.
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| JP3527255B2 true JP3527255B2 (en) | 2004-05-17 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP08754292A Expired - Fee Related JP3527255B2 (en) | 1992-03-12 | 1992-03-12 | 6-N-substituted aminopicolinic acid derivatives and their production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3527255B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017197433A (en) * | 2014-09-12 | 2017-11-02 | 石原産業株式会社 | Nicotinate compound, agricultural and horticultural bactericide, and method of controlling plant disease |
-
1992
- 1992-03-12 JP JP08754292A patent/JP3527255B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Ｔａｋｕｚｏ， ＨＩＳＡＮＯ ｅｔ ａｌ．，Ｃｈｅｍ． Ｐｈａｒｍ． Ｂｕｌｌ．，日本，１９７４年，Ｖｏｌ．２２， Ｎｏ．７，ｐ．１６１１−７ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05255255A (en) | 1993-10-05 |
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