JP2631644B2 - Production of heterocyclic compounds - Google Patents

Production of heterocyclic compounds

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Publication number
JP2631644B2
JP2631644B2 JP7258314A JP25831495A JP2631644B2 JP 2631644 B2 JP2631644 B2 JP 2631644B2 JP 7258314 A JP7258314 A JP 7258314A JP 25831495 A JP25831495 A JP 25831495A JP 2631644 B2 JP2631644 B2 JP 2631644B2
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JP
Japan
Prior art keywords
compound
formula
general formula
compounds
optionally substituted
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.)
Expired - Lifetime
Application number
JP7258314A
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Japanese (ja)
Other versions
JPH08198852A (en
Inventor
デイヴイツド・フイリツプ・アスルズ
アンドリユウ・フルード
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shell Internationale Research Maatschappij BV
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Shell Internationale Research Maatschappij BV
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/98—Nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3

Description

【発明の詳細な説明】DETAILED DESCRIPTION OF THE INVENTION

【０００１】[0001]

【発明の属する技術分野】本発明は、或置換されたジヒ
ドロピリジンおよびピリジン化合物の製造および新規な
ジヒドロピリジン化合物そのものに関する。該化合物は
除草性ピリジルイミダゾリノン化合物製造用中間体とし
て有用である。The present invention relates to the preparation of some substituted dihydropyridine and pyridine compounds and to the novel dihydropyridine compounds themselves. The compound is useful as an intermediate for producing a herbicidal pyridylimidazolinone compound.

【０００２】[0002]

【従来の技術】ピリジルイミダゾリン化合物は種々の文
献に除草剤および植物生長調節剤として開示されてい
る。例えばＥＰ−Ａ−４１６２３は広範囲の該化合物お
よびそれらの除草剤としての使用を開示しており、一方
ＥＰ−Ａ−４１６２４はそれらの植物生長調節剤として
の使用を開示している。該化合物の中でこれら明細書の
各々は特定的に２−（５−イソプロピル−５−メチル−
４−オキソ−２−イミダゾリン−２−イル）−５−エチ
ル−ニコチン酸および２−（５−イソプロピル−５−メ
チル−４−オキソ−２−イミダゾリン−２−イル）−５
−メチルニコチン酸を開示している。ＥＰ−Ａ−９５１
０５は該ピリジルイミダゾリン化合物が２，３−ピリジ
ンカルボン酸無水物から合成されうることを開示してお
り、そして該無水物を容易に与えるジカルボキシ化合物
それ自身はキノリン化合物を酸化条件にさらすことによ
り製造されうることが知られている。BACKGROUND OF THE INVENTION Pyridylimidazoline compounds are disclosed in various documents as herbicides and plant growth regulators. For example, EP-A-41623 discloses a wide range of such compounds and their use as herbicides, while EP-A-41624 discloses their use as plant growth regulators. Within the compounds, each of these specifications specifically refers to 2- (5-isopropyl-5-methyl-
4-oxo-2-imidazolin-2-yl) -5-ethyl-nicotinic acid and 2- (5-isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) -5
-Disclose methylnicotinic acid. EP-A-951
No. 05 discloses that the pyridylimidazoline compound can be synthesized from 2,3-pyridinecarboxylic anhydride, and the dicarboxy compound itself that readily gives the anhydride is obtained by subjecting the quinoline compound to oxidizing conditions. It is known that it can be manufactured.

【０００３】ＥＰ−Ａ−１６１２２１は式Ａ[0003] EP-A-1612221 has the formula A

【化６】 の化合物が、式Ｂのヒドラゾンと式Ｃのマレイン酸誘導
体を反応させて式Ｄの化合物を生成させ、これからＨ−
ＮＲ9 Ｒ10を除去することにより製造されうることを特
許請求している。基Ｒ1 ないしＲ10について広範囲の可
能性が請求されている。Embedded image Reacts a hydrazone of formula B with a maleic acid derivative of formula C to form a compound of formula D, from which H-
Claims can be made by removing NR 9 R 10 . A wide range of possibilities is claimed for the radicals R 1 to R 10 .

【化７】 式Ｃの化合物の基Ｘは、ジヒドロピリジル化合物Ｄを生
成する反応のためには塩素または臭素原子である。生成
する塩化水素酸または臭化水素酸を吸収するために、塩
基の存在が好ましいと述べられ、そしてすべての実施例
で用いられている。脱アミノはジオキサン中の酸の使用
により行なわれている。Embedded image The group X of the compound of formula C is a chlorine or bromine atom for the reaction to form the dihydropyridyl compound D. The presence of a base is stated to be preferred in order to absorb the resulting hydrochloric or hydrobromic acid and is used in all examples. Deamination is performed by using an acid in dioxane.

【０００４】ＥＰ−Ａ−１６１２２１の実施例の化合物
において、基Ｒ3 およびＲ4 は常に結合基を表し、それ
は通常式In the compounds of the examples of EP-A-162211, the groups R 3 and R 4 always represent a linking group, which is usually of the formula

【化８】 （Ｒは通常フェニル、α−シアノアルキルまたはα−カ
ルバモイルアルキルである）の基である。１つの実施例
では該結合基は酸素原子である。ＥＰ−Ａ−１６１２２
１は更に、ピリジルイミダゾリン化合物を合成しうる
２，３−ピリジンカルボン酸無水物を提供することに関
する。ＥＰ−Ａ−１６１２２１によれば、該無水物を製
造する方法は、Ｒ3 とＲ4 が結合して式Embedded image (R is usually phenyl, α-cyanoalkyl or α-carbamoylalkyl). In one embodiment, the linking group is an oxygen atom. EP-A-16122
No. 1 further relates to providing a 2,3-pyridinecarboxylic anhydride capable of synthesizing a pyridylimidazoline compound. According to EP-A-161221, the process for producing the anhydride comprises the steps of reacting R 3 and R 4

【化９】 の基を表す式Ｄの化合物を脱アミノ化して化合物Ｒ−Ｎ
Ｈ2 を失わせてジカルボキシ化合物を生成させることに
より誘導されるピリジル化合物の開環とそれに続く脱水
を含む。ＥＰ−Ａ−１６１２２１に開示されている反応
に必要な式Ｃの化合物はそれ自身合成されなければなら
ず、そしてこれは無水マレイン酸を式Ｒ−ＮＨ2 の化合
物で処理し、次に無水酢酸で処理し、次にハロゲン化す
ることにより達成しうる（ＥＰ−Ａ−４１６２４参
照）。Embedded image Deamination of a compound of formula D, which represents a group of the formula RN
Includes ring opening of the pyridyl compound induced by loss of H 2 to form the dicarboxy compound followed by dehydration. Compounds of formula C required for the reaction disclosed in EP-A-161221 has to be its own synthesis, and this will process the maleic anhydride with a compound of the formula R-NH 2, then acetic anhydride And then halogenating (see EP-A-41624).

【０００５】[0005]

【発明が解決しようとする課題】本発明は、そのような
２，３−ピリジンカルボン酸無水物を容易に製造しうる
ジヒドロピリジン化合物の簡単な製造方法に関する。さ
らに、本発明は、２，３−ピリジンカルボン酸ジエステ
ルの製造方法にも関する。SUMMARY OF THE INVENTION The present invention relates to a simple method for producing a dihydropyridine compound which can easily produce such a 2,3-pyridinecarboxylic acid anhydride. Furthermore, the present invention relates to a method for producing 2,3-pyridinecarboxylic acid diester.

【０００６】[0006]

【課題を解決するための手段】本発明によれば、一般式According to the present invention, the general formula

【化１０】 （式中、Ｒ1 は水素原子または場合により置換されてい
てもよいアルキルまたはシクロアルキル基を表し、Ｒ2
は場合により置換されていてもよいアルキルまたはシク
ロアルキル基を表し、Ｒ3 及びＲ4 の各々は独立に、場
合により置換されていてもよいアルキルまたはシクロア
ルキル基を表し、そしてＲ5 及びＲ6 の各々は独立に、
場合により置換されていてもよいアルキル、シクロアル
キル、アルケニル、アルキニル、アリールまたはアルア
ルキル基を表す）の化合物の製造方法において、一般式Embedded image (Wherein, R 1 represents a hydrogen atom or an optionally alkyl substituted, or cycloalkyl group, R 2
Represents an optionally substituted alkyl or cycloalkyl group, each of R 3 and R 4 independently represents an optionally substituted alkyl or cycloalkyl group, and R 5 and R 6 Each independently
An optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl or aralkyl group) of a compound of the general formula

【化１１】 のヒドラゾン化合物と一般式Embedded image Hydrazone compounds and general formulas

【化１２】 のジカルボキシレート化合物を反応させることを含む前
記製造方法が提供される。Embedded image The production method comprising reacting a dicarboxylate compound of the formula (I).

【０００７】従来技術が、とりわけ基The prior art is, inter alia,

【化１３】 を含む環化合物の生成、ハロゲン化、塩基触媒による付
加、酸触媒による脱アミノ化、および得られる化合物の
Ｒ−ＮＨ2 化合物脱離を伴う開環を含む無水マレイン酸
からの多数の工程を必要とする２，３−ピリジンカルボ
ン酸無水物へのルートを提供するのに対し、本発明は、
ハロゲン化、塩基の使用、または物質損失を伴う開環工
程を必要としない化合物への簡単で直接的なルートを提
供する。Embedded image Generation of ring compounds containing halides, required additional base-catalyzed deamidation with acid catalyst, and the resulting compound a number of steps from the maleic anhydride containing an open ring with elimination R-NH 2 compound Whereas, the present invention provides a route to 2,3-pyridinecarboxylic anhydride
It provides a simple and direct route to compounds that do not require halogenation, use of a base, or a ring opening step with material loss.

【０００８】本発明の方法によれば、アルキル、アルケ
ニルまたはアルキニル基は好ましくは１ないし６、特に
１ないし４個の炭素原子を有し、一方シクロアルキル基
は好ましくは３ないし８個の炭素原子を有する。アリー
ル基は好ましくはフェニルであり、そしてアルアルキル
基は好ましくはベンジルである。基が置換されている場
合、可能な置換基は例えばハロゲン原子、Ｃ1-4 アルコ
キシまたはハロアルコキシ基、ヒドロキシ、シアノ、ア
ミノ、アルキルアミノ、フェニル、フェノキシ、カルボ
キシおよびアルコキシカルボニル基を含みうる。しかし
一般に、各置換基Ｒ2 ないしＲ6 は未置換基であるのが
好ましく、そして好ましくは未置換Ｃ1-4 アルキル基で
あり、メチルおよびエチルが最も好ましい基であり、一
方Ｒ1 は好ましくは水素原子である。好ましくは反応は
テトラヒドロフラン、アセトニトリルまたはジオキサ
ン、または適当にはトルエンまたはキシレンのようなア
ルキル化ベンゼンといった不活性有機溶媒中で行なわれ
る。反応は０℃ないし還流温度（これは使用溶媒によっ
て７０℃ないし１４０℃が適当でありうる）で行なうこ
とができ、そして有利には５０℃ないし還流温度の範囲
で、最も好ましくは還流温度で行なわれる。ヒドラゾン
がジカルボキシレートに対しモル過剰であるのが好まし
い。しかしそうでない場合でも反応は充分に進行しう
る。一般にヒドラゾン対ジカルボキシレートの好ましい
モル比は１：１ないし２：１特に１：１ないし１．５：
１の範囲である。According to the process of the invention, the alkyl, alkenyl or alkynyl group preferably has 1 to 6, especially 1 to 4, carbon atoms, while the cycloalkyl group preferably has 3 to 8 carbon atoms Having. Aryl groups are preferably phenyl and aralkyl groups are preferably benzyl. If the group is substituted, possible substituents may include, for example, halogen atoms, C 1-4 alkoxy or haloalkoxy groups, hydroxy, cyano, amino, alkylamino, phenyl, phenoxy, carboxy and alkoxycarbonyl groups. In general, however, each substituent R 2 to R 6 is preferably unsubstituted, and is preferably an unsubstituted C 1-4 alkyl group, with methyl and ethyl being the most preferred groups, while R 1 is preferably Is a hydrogen atom. Preferably, the reaction is carried out in an inert organic solvent such as tetrahydrofuran, acetonitrile or dioxane, or suitably an alkylated benzene such as toluene or xylene. The reaction can be carried out at a temperature between 0 ° C. and the reflux temperature, which may suitably be 70 ° C. to 140 ° C., depending on the solvent used, and is advantageously carried out in the range from 50 ° C. to the reflux temperature, most preferably at the reflux temperature. It is. Preferably, the hydrazone is in a molar excess over the dicarboxylate. However, if not, the reaction can proceed sufficiently. In general, the preferred molar ratio of hydrazone to dicarboxylate is from 1: 1 to 2: 1, especially from 1: 1 to 1.5:
1 range.

【０００９】他の面では本発明は式Ｉの化合物自体に関
する。一般式Ｉの化合物は脱アミノ条件下に一般式In another aspect, the invention relates to the compounds of formula I per se. Compounds of general formula I have the general formula

【化１４】 のピリジン化合物に転化しうる。好ましくは反応はベン
ゼン、トルエンまたはキシレンのような不活性有機溶媒
中で、好都合には木炭基質に担持されうるパラジウムま
たは白金のような触媒の存在下に行なわれる。好ましく
は、反応は昇温下で、適当には５０℃ないし還流温度の
範囲で、最も好ましくは還流温度で行なわれる。Embedded image To a pyridine compound. Preferably, the reaction is carried out in an inert organic solvent such as benzene, toluene or xylene, conveniently in the presence of a catalyst such as palladium or platinum, which can be supported on a charcoal substrate. Preferably, the reaction is carried out at elevated temperature, suitably in the range of 50 ° C to reflux temperature, most preferably at reflux temperature.

【００１０】他の面では本発明は、５−メチル−２，３
−ピリジンカルボン酸ジエチルエステルを除く該新規ピ
リジン化合物自体に関する。一般式IVの化合物は、例え
ばそれらを水性水酸化ナトリウム中で対応するジカルボ
ン酸に転化し、酸を、適当には無水酢酸の存在下に還流
することにより、酸無水物に転化し、そして次にＥＰ−
Ａ−９５１０５に開示されている方法により、除草性ピ
リジルイミダゾリニル化合物を生成させるのに使用しう
る。[0010] In another aspect, the present invention provides 5-methyl-2,3
The novel pyridine compounds themselves, excluding pyridinecarboxylic acid diethyl ester. The compounds of the general formula IV can be converted into the acid anhydrides, for example by converting them into the corresponding dicarboxylic acids in aqueous sodium hydroxide, by refluxing the acids, suitably in the presence of acetic anhydride, and To EP-
It can be used to produce herbicidal pyridylimidazolinyl compounds by the method disclosed in A-95105.

【００１１】[0011]

【発明の実施の形態】例１ ４Ｈ−１−ジメチルアミノ−２，３−ジカルボキシ−５
−メチルジヒドロピリジン、ジメチルエステルの製造 アセチレンジカルボン酸ジメチル（１７．３ｇ；０．１
２２モル）および２−メチルプロプ−２−エナール・ジ
メチルヒドラゾン（１５．０ｇ；０．１３４モル）を乾
燥トルエン２０mlに添加した。反応混合物を窒素雰囲気
下１時間還流させた。溶媒を蒸発させた。溶離剤として
３５−４０％（ｖ／ｖ）酢酸エチル／ｎ−ヘキサンを使
用するシリカ上でのカラムクロマトグラフィは標記化合
物を黄色油（６．９ｇ）として生じ、これは冷凍すると
結晶化した（融点ｃ．５０℃）。分析 所要値（％） ５６．７Ｃ ７．１Ｈ １１．０Ｎ 測定値（％） ５６．５Ｃ ７．２Ｈ １１．０ＮDETAILED DESCRIPTION OF THE INVENTION Example 1 4H-1-dimethylamino-2,3-dicarboxy-5
-Preparation of methyldihydropyridine, dimethyl ester Dimethyl acetylenedicarboxylate (17.3 g; 0.1
22 mol) and 2-methylprop-2-enal dimethylhydrazone (15.0 g; 0.134 mol) were added to 20 ml of dry toluene. The reaction mixture was refluxed for 1 hour under a nitrogen atmosphere. The solvent was evaporated. Column chromatography on silica using 35-40% (v / v) ethyl acetate / n-hexane as eluent gave the title compound as a yellow oil (6.9 g) which crystallized on freezing (mp c. 50 ° C). Analysis required value (%) 56.7C 7.1H 11.0N Measured value (%) 56.5C 7.2H 11.0N

【００１２】例２ ４−Ｈ−１−ジメチルアミノ−２，３−ジカルボキシ−
５−エチルジヒドロピリジン、ジメチルエステルの製造 アセチレンジカルボン酸ジメチル（２０．５ｇ；０．１
４４モル）および２−エチルプロプ−２−エナール・ジ
メチルヒドラゾン（２０．０ｇ；０．１５９モル）を乾
燥トルエン２５mlに添加した。反応混合物を１時間還流
させた。溶媒を蒸発により除去した。溶離剤として４
０．５％（ｖ／ｖ）酢酸エチル／ｎ−ヘキサンを使用す
るシリカ上のカラムクロマトグラフィは標記化合物を橙
色油（７．７ｇ）として生じた。分析 所要値（％） ５８．２Ｃ ７．５Ｈ １０．４Ｎ 測定値（％） ５６．８Ｃ ７．７Ｈ ９．６Ｎ Example 2 4-H-1-dimethylamino-2,3-dicarboxy-
Preparation of 5- ethyldihydropyridine , dimethyl ester Dimethyl acetylenedicarboxylate (20.5 g; 0.1
44 mol) and 2-ethylprop-2-enal dimethylhydrazone (20.0 g; 0.159 mol) were added to 25 ml of dry toluene. The reaction mixture was refluxed for 1 hour. The solvent was removed by evaporation. 4 as eluent
Column chromatography on silica using 0.5% (v / v) ethyl acetate / n-hexane provided the title compound as an orange oil (7.7 g). Analysis required value (%) 58.2C 7.5H 10.4N Measurement value (%) 56.8C 7.7H 9.6N

【００１３】例３ ２，３−ジカルボキシ−５−メチルピリジン、ジメチル
エステルの製造 例１の標題化合物（６．５ｇ）を乾燥トルエン５０mlに
溶解しそして５％ｗ／ｗパラジウム炭（０．６ｇ）を触
媒として添加した。反応混合物を、２時間毎に触媒を補
充して１４時間還流させた。反応混合物を濾過しそして
溶媒を蒸発させて赤褐色油（７．０ｇ）を残した。溶離
剤として４０％（ｖ／ｖ）酢酸エチル／ｎ−ヘキサンを
使用するシリカ上でのカラムクロマトグラフィは標記化
合物（３．３５ｇ）を固体（融点５９−６０℃）として
生じた。分析 所要値（％） ５８．９Ｃ ３．１Ｈ ８．６Ｎ 測定値（％） ５８．７Ｃ ３．７Ｈ ８．０Ｎ Example 3 2,3-Dicarboxy-5-methylpyridine, dimethyl
Ester Preparation The title compound of Example 1 (6.5 g) was dissolved in 50 ml of dry toluene and 5% w / w palladium on carbon (0.6 g) was added as a catalyst. The reaction mixture was refluxed for 14 hours, replenishing the catalyst every 2 hours. The reaction mixture was filtered and the solvent was evaporated, leaving a reddish brown oil (7.0 g). Column chromatography on silica using 40% (v / v) ethyl acetate / n-hexane as eluent gave the title compound (3.35 g) as a solid (mp 59-60 ° C). Analysis required value (%) 58.9C 3.1H 8.6N Measured value (%) 58.7C 3.7H 8.0N

【００１４】例４ 例２の標題化合物（７．４５ｇ）を乾燥トルエン７５ml
に溶解しそして５％ｗ／ｗパラジウム炭（０．７５ｇ）
を触媒として添加した。反応混合物を窒素雰囲気下、１
７および１９時間後に触媒を補充して２１時間還流させ
た。反応混合物を濾過しそして溶媒を蒸発させた。得ら
れた油（６ｇ）の、３５−４０％（ｖ／ｖ）酢酸エチル
／ｎ−ヘキサンを用いるシリカ上のカラムクロマトグラ
フィは標記化合物を橙色油（３．４ｇ）として生じた。分析 所要値（％） ５９．２Ｃ ５．８Ｈ ６．３Ｎ 測定値（％） ５７．８Ｃ ５．８Ｈ ６．５Ｎ 上記手順を繰り返した時、４．６ｇの出発物質から３．
４９ｇの標記化合物が得られた。 Example 4 75 ml of dry toluene was obtained by adding the title compound of Example 2 (7.45 g).
And 5% w / w palladium on charcoal (0.75 g)
Was added as a catalyst. The reaction mixture is placed under a nitrogen atmosphere,
After 7 and 19 hours, the catalyst was replenished and refluxed for 21 hours. The reaction mixture was filtered and the solvent was evaporated. Column chromatography of the resulting oil (6 g) on silica using 35-40% (v / v) ethyl acetate / n-hexane gave the title compound as an orange oil (3.4 g). Analysis required (%) 59.2C 5.8H 6.3N Measured (%) 57.8C 5.8H 6.5N When the above procedure was repeated, 4.6 g of starting material was obtained.
49 g of the title compound were obtained.

【００１５】次の実施例は式IVの化合物が、ＥＰ−Ａ−
９５１０５のピリジンイミダゾリニル化合物の合成に使
用しうる酸無水物化合物にどのようにして転化しうるか
を説明する。 例５２，３−カルボキシ−５−メチルピリジン無水物の製造 例３の標題化合物（７．９５ｇ）を１０％ｗ／ｗ水性水
酸化ナトリウム（３５ml）に添加した。反応混合物を１
1/2 時間還流させそして冷却した。反応混合物のpHが２
になるまで濃塩酸を添加した。冷却して生じた淡褐色沈
澱を濾過し乾燥した（２．１５ｇ）。pHが１になるまで
更に塩酸を添加した。更に生成した沈澱（０．９５ｇ）
を濾過し乾燥した。２．１５ｇの沈澱（２，３−ジカル
ボキシ−５−メチルピリジン）を無水酢酸（３５ml；密
度１．０８２ｇ／l ）に溶解した。反応混合物を２1/2
時間還流した。無水酢酸を最初蒸発により、次に熱水浴
および真空ポンプにより分離して淡灰色固体を得た。分析 所要値（％） ５８．９Ｃ ３．１Ｈ ８．６Ｎ 測定値（％） ５８．７Ｃ ３．７Ｈ ８．０ＮThe following example shows that a compound of formula IV has the formula EP-A-
An explanation will be given as to how 9595 can be converted to an acid anhydride compound which can be used for the synthesis of a pyridine imidazolinyl compound. Example 5 Preparation of 2,3-carboxy-5-methylpyridine anhydride The title compound of Example 3 (7.95 g) was added to 10% w / w aqueous sodium hydroxide (35 ml). 1 reaction mixture
Refluxed for 1/2 hr and cooled. When the pH of the reaction mixture is 2
Concentrated hydrochloric acid was added until the mixture became. The light brown precipitate formed on cooling was filtered and dried (2.15 g). More hydrochloric acid was added until the pH reached 1. Further precipitation (0.95 g)
Was filtered and dried. 2.15 g of the precipitate (2,3-dicarboxy-5-methylpyridine) were dissolved in acetic anhydride (35 ml; density 1.082 g / l). The reaction mixture 2 1/2
Refluxed for hours. The acetic anhydride was separated off first by evaporation, then by a hot water bath and a vacuum pump to give a light gray solid. Analysis required value (%) 58.9C 3.1H 8.6N Measured value (%) 58.7C 3.7H 8.0N

───────────────────────────────────────────────────── フロントページの続き (72)発明者 アンドリユウ・フルード イギリス国ケント州 エムイー10 １エ ヌエフ、シツテイングボーン、ロンド ン・ロード、ホリイバンク・ヒル 25 (56)参考文献 特開 昭62−106081（ＪＰ，Ａ) ────────────────────────────────────────────────── ─── Continuing from the front page (72) Inventor Andriyu Flud EMU 101, Kent, UK, Sittingbourne, London Road, Hollybank Hill 25 (56) References JP, A)

Claims (1)

(57)【特許請求の範囲】(57) [Claims] 【請求項１】 一般式 【化１】 （式中、Ｒ１は水素原子または場合により置換されてい
てもよいアルキルまたはシクロアルキル基を表し、 Ｒ２は場合により置換されていてもよいアルキルまたは
シクロアルキル基を表し、 Ｒ３及びＲ４の各々は独立に、場合により置換されてい
てもよいアルキルまたはシクロアルキル基を表し、そし
て Ｒ５及びＲ６の各々は独立に、場合により置換されてい
てもよいアルキル、シクロアルキル、アルケニル、アル
キニル、アリールまたはアルアルキル基を表す）の化合
物を、一般式 【化２】 のヒドラゾン化合物と一般式 【化３】 のジカルボキシレート化合物を反応させて製造し、続い
て一般式Ｉの化合物を脱アミノ化して一般式 【化４】 の化合物を製造する方法。1. A compound of the general formula (Wherein, R 1 represents a hydrogen atom or an optionally substituted alkyl or cycloalkyl group, R 2 represents an optionally substituted alkyl or cycloalkyl group, R 3 and R 4 Each independently represents an optionally substituted alkyl or cycloalkyl group, and each of R 5 and R 6 independently represents an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl group. , An aryl or aralkyl group) of the general formula: A hydrazone compound of the general formula By reacting a dicarboxylate compound of the general formula I, followed by deamination of the compound of the general formula I to give the general formula A method for producing a compound of the formula:
JP7258314A 1986-03-10 1995-09-12 Production of heterocyclic compounds Expired - Lifetime JP2631644B2 (en)

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JP2019502729A (en) * 2016-01-22 2019-01-31 ダウ アグロサイエンシィズ エルエルシー Process for producing 4-alkoxy-3-hydroxypicolinic acid

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EP0067511A3 (en) * 1981-05-19 1983-04-06 Imperial Chemical Industries Plc Method of inducing tillering using pyridine derivatives, and some of the pyridines themselves, process for preparing them and agricultural compositions containing them
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US4754033A (en) * 1984-08-10 1988-06-28 Ciba-Geigy Corporation Process for producing pyridine-2,3-dicarboxylic acid derivatives; and novel 1-amino-1,2,3,4-tetrahydropyridine-2,3-dicarboxylic acid derivatives and 1,4-dihydropyridine-2,3-dicarboxylic acid derivatives
EP0221023A3 (en) * 1985-10-25 1988-11-09 Ciba-Geigy Ag Process for the preparation of pyridine-2-carboxylic-acid derivatives and 1-amino-1,4-dihydropyridine-2-carboxylic-acid derivatives
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JPH08198852A (en) 1996-08-06
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BE1003158A5 (en) 1991-12-17
JPH0832683B2 (en) 1996-03-29
GB2188318B (en) 1990-02-14
GB8605868D0 (en) 1986-04-16
JPS62212368A (en) 1987-09-18
CH671762A5 (en) 1989-09-29
FR2595354B1 (en) 1993-11-26
GB2188318A (en) 1987-09-30
FR2595354A1 (en) 1987-09-11
GB8705472D0 (en) 1987-04-15

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