JPH0477470A - Production of 2-methoxy-6-methylaminopyridine - Google Patents
Production of 2-methoxy-6-methylaminopyridineInfo
- Publication number
- JPH0477470A JPH0477470A JP18728390A JP18728390A JPH0477470A JP H0477470 A JPH0477470 A JP H0477470A JP 18728390 A JP18728390 A JP 18728390A JP 18728390 A JP18728390 A JP 18728390A JP H0477470 A JPH0477470 A JP H0477470A
- Authority
- JP
- Japan
- Prior art keywords
- methylaminopyridine
- solution
- methylamine
- reaction
- temperature
- 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.)
- Pending
Links
- GXHQLRBOZRJHPZ-UHFFFAOYSA-N 6-methoxy-n-methylpyridin-2-amine Chemical compound CNC1=CC=CC(OC)=N1 GXHQLRBOZRJHPZ-UHFFFAOYSA-N 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 75
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims abstract description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 60
- 239000000243 solution Substances 0.000 claims abstract description 33
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 239000007864 aqueous solution Substances 0.000 claims abstract description 15
- 239000011874 heated mixture Substances 0.000 claims abstract description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 4
- SVEUVITYHIHZQE-UHFFFAOYSA-N n-methylpyridin-2-amine Chemical compound CNC1=CC=CC=N1 SVEUVITYHIHZQE-UHFFFAOYSA-N 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 53
- VPGPNOQDNGMIKA-UHFFFAOYSA-N 6-chloro-n-methylpyridin-2-amine Chemical compound CNC1=CC=CC(Cl)=N1 VPGPNOQDNGMIKA-UHFFFAOYSA-N 0.000 abstract description 27
- 230000032683 aging Effects 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 5
- 239000000047 product Substances 0.000 abstract description 5
- 238000001816 cooling Methods 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 abstract description 2
- 239000006227 byproduct Substances 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 13
- 238000010438 heat treatment Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は２−メトキシ−６−メチルアミノピリジンの製
造法に関する。２−メトキシ−６−メチルアミノピリジ
ンは医薬、農薬中間体として重要な化合物である。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing 2-methoxy-6-methylaminopyridine. 2-Methoxy-6-methylaminopyridine is an important compound as an intermediate for pharmaceuticals and agricultural chemicals.
〈従来技術〉
従来の製造法としては、２，６−ジクロロピリジンとメ
チルアミン水溶液を混合の後、加熱、反応させる方法（
特公昭６３−４４７４８号公報）、並びに、２−クロロ
−６−メチルアミノピリジン、水酸化ナトリウム並びに
メタノールを混合の後、加熱、反応させる方法（特開昭
６２−７２６６７号公報）、さらには、２．６−ジクロ
ロピリジンとメチルアミン水溶液の反応液よりメチルア
ミンを回収した後、芳香族炭化水素で抽出、濃縮し、次
いで、メタノール並びに水酸化ナトリウムと反応させる
方法（特開平２−１５０６３号公報）等数多くの製造法
が知られている。<Prior art> The conventional manufacturing method is to mix 2,6-dichloropyridine and methylamine aqueous solution, then heat and react (
Japanese Patent Publication No. 63-44748), and a method of mixing 2-chloro-6-methylaminopyridine, sodium hydroxide, and methanol and then heating and reacting (Japanese Patent Publication No. 62-72667), 2. A method in which methylamine is recovered from a reaction solution of 6-dichloropyridine and an aqueous methylamine solution, extracted with an aromatic hydrocarbon, concentrated, and then reacted with methanol and sodium hydroxide (JP-A-2-15063) ) and many other manufacturing methods are known.
〈従来技術の課題〉
特公昭６３−４４７４８号公報に記載された方法におい
ては、２，６−ジクロロピリジンとメチルアミン水溶液
の反応は発熱反応のため、工業的規模で実施する場合、
反応温度の制御が困難となり、温度上昇により、反応に
悪影響を与える場合があるばかりか、高温、高圧が発生
し、危険な状態となる場合がある。<Problems with the Prior Art> In the method described in Japanese Patent Publication No. 63-44748, the reaction between 2,6-dichloropyridine and methylamine aqueous solution is an exothermic reaction, so when carried out on an industrial scale,
It becomes difficult to control the reaction temperature, and the rise in temperature may not only adversely affect the reaction, but also generate high temperatures and pressures, which may lead to a dangerous situation.
同様に、特開昭６２−７２６６７号公報に記載された方
法においても、２−クロロ−６−メチルアミノピリジン
、メタノール並びに水酸化ナトリウムの反応も発熱反応
のため、工業的規模で実施した場合、反応温度の制御が
困難となり、温度上昇により、反応に悪影響を与える場
合があるばかりか、高温、高圧が発生し、危険な状態と
なる場合かある。Similarly, in the method described in JP-A-62-72667, the reaction of 2-chloro-6-methylaminopyridine, methanol, and sodium hydroxide is also an exothermic reaction, so when carried out on an industrial scale, It becomes difficult to control the reaction temperature, and the temperature rise may not only adversely affect the reaction, but also generate high temperatures and pressures, which may result in a dangerous situation.
さらに、特公昭６３−４４７４８号公報等に記載された
方法は、２，６−ジクロロピリジンとメチルアミン水溶
液の反応後、生成物２−クロロ６−メチルアミンピリジ
ンを固体として得るため、晶析操作等により、スケール
の発生する場合かあり、工業的には好ましくない。Furthermore, in the method described in Japanese Patent Publication No. 63-44748, etc., after the reaction of 2,6-dichloropyridine and an aqueous methylamine solution, a crystallization operation is performed to obtain the product 2-chloro6-methylaminepyridine as a solid. As a result, scale may be generated, which is not preferred industrially.
加えて、特開平２−１５０６３号公報に記載された方法
は特公昭６３−４４７４８号公報に記載され方法を改良
するものであるか、反応は、特公昭６３−４４７４８号
公報並びに特開昭６２−７２６６７号公報と同じ方法で
あるため、同様の問題が発生する可能性がある。In addition, the method described in JP-A-2-15063 is an improvement on the method described in JP-A-63-44748, or the reaction is similar to that described in JP-A-63-44748 and JP-A-62. Since this method is the same as that of Publication No. 72667, similar problems may occur.
く課題を解決するための手段〉
本発明者らは、２，６−ジクロロピリジンより２−メト
キシ−６−メチルアミノピリジンの製造法について鋭意
検討した結果、２．６−ジクロロピリジンとメチルアミ
ンの反応においては、メチルアミン水溶液を加熱した２
、６−ジクロロピリジンに供給することにより、反応温
度の制御か可能で、後処理として、水酸化ナトリウム水
溶液を添加し、過剰のメチルアミンを回収した後、有機
溶媒で抽出することにより、スケール発生等の問題がな
く、さらに、得られた反応液を原料とし、抽出した液を
濃縮することなくまたは、適度に濃縮した後、さらに必
要に応じてメタノールを添加した後、引き続き加熱した
メタノール並びに水酸化ナトリウムの混合物に供給、反
応させることにより、目的物２−メトキシ−６−メチル
アミノピリジンに同等悪影響なく、また、反応温度制御
か容易であることを見出だし本発明を完成させるに至っ
た。Means for Solving the Problems> As a result of intensive study on the method for producing 2-methoxy-6-methylaminopyridine from 2,6-dichloropyridine, the present inventors found that In the reaction, a methylamine aqueous solution was heated to 2
, 6-dichloropyridine, the reaction temperature can be controlled, and as a post-treatment, an aqueous sodium hydroxide solution is added, excess methylamine is recovered, and then extracted with an organic solvent to prevent scale generation. Furthermore, using the obtained reaction liquid as a raw material, the extracted liquid can be used without concentrating it or after concentrating it appropriately, and then adding methanol as necessary, followed by heated methanol and water. The present inventors have discovered that by supplying a mixture of sodium oxide and causing the reaction, the target product, 2-methoxy-6-methylaminopyridine, is not adversely affected, and the reaction temperature can be easily controlled, leading to the completion of the present invention.
即ち、本発明は、加熱した２、６−ジクロロピリジンに
メチルアミン水溶液を供給し反応させた後、水酸化ナト
リウム水溶液を添加し、メチルアミンを回収、次いで有
機溶媒で抽出することにより２−クロロ−６−メチルア
ミノピリジンの有機溶媒溶液を得、さらに引き続き、加
熱した、メタノール並びに水酸化ナトリウム混合物に２
−クロロ−６−メチルアミノピリジンの有機溶媒溶液ま
たはその濃縮液、或いは溶液または濃縮液にメタノール
を添加したものを供給し反応させることを特徴とする２
−メトキシ−６−メチルアミノピリジンの製造法を提供
するものである。That is, in the present invention, a methylamine aqueous solution is supplied to heated 2,6-dichloropyridine and reacted, an aqueous sodium hydroxide solution is added, methylamine is recovered, and 2-chloropyridine is extracted by extraction with an organic solvent. A solution of -6-methylaminopyridine in an organic solvent was obtained, and then added to a heated mixture of methanol and sodium hydroxide.
2, characterized in that a solution of chloro-6-methylaminopyridine in an organic solvent or a concentrate thereof, or a solution or concentrate to which methanol is added is supplied and reacted.
A method for producing -methoxy-6-methylaminopyridine is provided.
く作用〉 以下、本発明の詳細な説明する。Effect〉 The present invention will be explained in detail below.
本発明は、２，６−ジクロロピリジンとメチルアミンの
反応工程と、得られた２−クロロ−６−メチルアミノピ
リジンとメタノール並びに水酸化ナトリウムの反応工程
の２工程よりなる。The present invention consists of two steps: a step of reacting 2,6-dichloropyridine with methylamine, and a step of reacting the obtained 2-chloro-6-methylaminopyridine with methanol and sodium hydroxide.
以下、前記工程を第一工程１．後記工程を第二工程と略
す。Hereinafter, the above steps will be described as the first step 1. The process described below will be abbreviated as the second process.
ます、第一工程について記述する。First, the first step will be described.
本発明の反応に使用するメチルアミンは２．６−ジクロ
ロピリジンに対して、２倍モル量以上であれば可能であ
るが、反応速度または経済性の面で好ましくは２．０〜
５．０倍モル量の範囲である。ま、た、水溶液中の濃度
は、１０重量％以上飽和溶液以下であれば可能であるが
、４０重量％以上では常温、常圧下で飽和溶解度以上と
なるため好ましくない。The amount of methylamine used in the reaction of the present invention can be at least twice the molar amount of 2,6-dichloropyridine, but from the viewpoint of reaction rate or economy, it is preferably 2.0 to 2.6-dichloropyridine.
The range is 5.0 times the molar amount. Further, the concentration in the aqueous solution can be 10% by weight or more and below the saturated solution, but if it is 40% by weight or more, it is not preferable because it will exceed the saturated solubility at room temperature and normal pressure.
メチルアミン水溶液供給時の反応器内温度は、反応が進
行する温度であれば問題なく、好ましくは８０℃〜１５
０℃の範囲であり、８０℃以下ては反応か進行せず、ま
た１５０℃以上では分解により収率が低下する場合かあ
る。There is no problem with the temperature inside the reactor when feeding the methylamine aqueous solution as long as the reaction proceeds, preferably 80°C to 15°C.
The reaction temperature is in the range of 0°C, and below 80°C, the reaction does not proceed, and above 150°C, the yield may decrease due to decomposition.
メチルアミンの供給速度は供給時の反応器内温度、メチ
ルアミンの水溶液中濃度により異なるが通常１〜８時間
の範囲であれば良い。The feeding rate of methylamine varies depending on the temperature inside the reactor at the time of feeding and the concentration of methylamine in the aqueous solution, but it is usually within the range of 1 to 8 hours.
メチルアミンの供給終了後の熟成温度並びに時間は、メ
チルアミンの供給時の反応器内温度、メチルアミン水溶
液濃度、メチルアミンの２．６−ジクロロピリジンに対
する使用量等の反応条件により異なるが、通常、１３０
〜１５０℃で８時間以内の熟成を行うことにより反応は
完結する。The ripening temperature and time after the end of methylamine supply varies depending on reaction conditions such as the temperature inside the reactor when methylamine is supplied, the concentration of the methylamine aqueous solution, and the amount of methylamine used relative to 2,6-dichloropyridine, but usually , 130
The reaction is completed by aging at ~150°C for up to 8 hours.
第一工程の反応終了後、反応液を１００℃以下に冷却の
後、余剰メチルアミンをガスとして回収した後、さらに
、使用した２、６−ジクロロピリジンに対して等モル２
以上１０倍モル量以下の水酸化ナトリウムを１０〜４８
％含有する水溶液を供給し、副生じたメチルアミンの塩
酸塩をメチルアミンとすることにより、ガスとして回収
の後、使用する有機溶媒の沸点以下に冷却、次いで所定
量の有機溶媒を添加する。After the reaction of the first step was completed, the reaction solution was cooled to 100°C or less, excess methylamine was recovered as a gas, and then 2 mols of
10 to 48 times more than 10 times the molar amount of sodium hydroxide
%, and the by-produced methylamine hydrochloride is converted into methylamine. After recovery as a gas, it is cooled to below the boiling point of the organic solvent used, and then a predetermined amount of the organic solvent is added.
添加する有機溶媒の種類としては、２−クロロ−６−メ
チルアミノピリジンを溶解する溶媒であればあらゆるも
のが使用可能であり、例えば、トルエン、ベンゼン、キ
シレン、エチルベンゼン、メシチレン等の芳香族炭化水
素類、クロロホルム、ジクロロメタン、ジクロロエタン
等の／％ロゲン化炭化水素類、ペンタン、ヘキサン、ヘ
プタン、オクタン、シクロペンタン、シクロヘキサン等
の脂肪族炭化水素、ジエチルエーテル、ジイソブチルエ
ーテル等のエーテル類、メチルエチルケトン等のケトン
類が挙げられるが、目的物２−クロロ−６−メチルアミ
ノピリジンの溶解性並びに工業上の安全性等の面で、好
ましくは芳香族炭化水素である。As for the type of organic solvent to be added, any solvent that dissolves 2-chloro-6-methylaminopyridine can be used. For example, aromatic hydrocarbons such as toluene, benzene, xylene, ethylbenzene, mesitylene, etc. chloroform, dichloromethane, dichloroethane, etc., aliphatic hydrocarbons such as pentane, hexane, heptane, octane, cyclopentane, cyclohexane, ethers such as diethyl ether, diisobutyl ether, and ketones such as methyl ethyl ketone. However, aromatic hydrocarbons are preferable from the viewpoint of solubility of the target product 2-chloro-6-methylaminopyridine and industrial safety.
使用する有機溶媒の量は、溶媒の種類、抽出温度により
異なるるか、通常２−クロロ−６−メチルアミノピリジ
ンに対して、０．５〜５，０重量量倍量使用し、抽出は
使用する溶媒の沸点以下で尚且つ、２−クロロ−６−メ
チルアミノピリジンが完全に溶解する温度以上で行う。The amount of organic solvent used varies depending on the type of solvent and extraction temperature, but is usually 0.5 to 5.0 times the weight of 2-chloro-6-methylaminopyridine. The temperature is below the boiling point of the solvent used and above the temperature at which 2-chloro-6-methylaminopyridine is completely dissolved.
抽出した２−クロロ−６−メチルアミノピリジンの溶液
は、芳香族炭化水素類並びに脂肪族炭化水素類のように
、第二工程の反応に影響の無い溶媒であれば、そのまま
使用してもかまはないし、また濃縮して使用してもかま
はない。さらに、ハロゲン化炭化水素類、ケトン類のよ
うに第二工程で反応に影響する溶媒であれば、影響のな
くなる程度まで濃縮の後、第二工程に使用する。The extracted solution of 2-chloro-6-methylaminopyridine can be used as is as long as it is a solvent that does not affect the reaction in the second step, such as aromatic hydrocarbons and aliphatic hydrocarbons. There is no problem with it, and there is no problem with concentrating it and using it. Furthermore, if the solvent affects the reaction in the second step, such as halogenated hydrocarbons and ketones, it is used in the second step after being concentrated to such an extent that the effect disappears.
次いで、第二工程について記述する。Next, the second step will be described.
第二工程は、反応器内に所定量のメタノール、水酸化ナ
トリウムを仕込んだ後、加熱し、これに前記抽出した２
−クロロ−６−メチルアミノピリジンの溶液、加熱溶解
した濃縮液さらに溶液または濃縮液にメタノールを添加
したものを供給し反応を行う。In the second step, a predetermined amount of methanol and sodium hydroxide are charged into the reactor, heated, and the extracted 2
A solution of -chloro-6-methylaminopyridine, a concentrated solution dissolved by heating, and a solution or concentrated solution to which methanol is added are supplied to carry out the reaction.
反応に使用するメタノールの量は、あらかじめ反応器に
仕込む量と、２−クロロ−６−メチルアミノピリジンを
溶解し反応に用いる場合はその総量として、２−クロロ
−６−メチルアミンピリジンに対して、３．０〜７．０
倍モル量の範囲が適用可能である。The amount of methanol used in the reaction is based on the amount charged in advance to the reactor and the total amount when 2-chloro-6-methylaminopyridine is dissolved and used in the reaction, relative to 2-chloro-6-methylaminepyridine. , 3.0-7.0
A range of double molar amounts is applicable.
使用する水酸化ナトリウムの量は、２−クロロ−６−メ
チルアミノピリジンに対して１．０倍モル以上で適用可
能であるが、１．５倍モル量以下では反応に長時間要し
好ましくなくまた、５．０倍モル量以上では反応に顕著
な効果が見られないため経済的ではない。従って、１．
５〜５．０倍モル量の範囲が好ましい。The amount of sodium hydroxide used can be at least 1.0 times the molar amount of 2-chloro-6-methylaminopyridine, but if it is less than 1.5 times the molar amount, the reaction will take a long time, which is undesirable. Moreover, if the amount is 5.0 times or more by molar amount, no significant effect on the reaction will be observed, so it is not economical. Therefore, 1.
A range of 5 to 5.0 times the molar amount is preferred.
また、反応前、あらかじめ反応器に仕込むメタノールは
、水酸化ナトリウムに対して、０．１〜６．５倍重量の
範囲であれば良いか、攪拌等の問題で好ましくは０．５
〜２．５倍重量の範囲である。In addition, methanol charged in advance to the reactor before the reaction may be in the range of 0.1 to 6.5 times the weight of sodium hydroxide, or preferably 0.5 times due to problems such as stirring.
~2.5 times the weight.
２−クロロ−６−メチルアミノピリジンの供給方法とし
ては、第一工程で得られた反応液が常温で固体を析出す
る場合、または、濃縮液を用いる場合は、加熱溶解また
は、加熱溶融し、反応器へ供給する。メタノールを添加
する場合の添加量は２−クロロ−６−メチルアミノピリ
ジンに対して４倍モル量以下であり、あらかじめ反応器
内に仕込むメタノールとの総量として７．０倍モル量以
下となる量であれば良い。As a method for supplying 2-chloro-6-methylaminopyridine, if the reaction solution obtained in the first step precipitates a solid at room temperature, or if a concentrated solution is used, melting by heating or melting by heating, Feed to reactor. When methanol is added, the amount to be added is 4 times the molar amount or less relative to 2-chloro-6-methylaminopyridine, and the total amount with the methanol charged in advance in the reactor is 7.0 times the molar amount or less. That's fine.
２−クロロ−６−メチルアミノピリジンを溶液として供
給する場合で、常温で固体が析出する場合は、その溶解
温度以上、使用する有機溶媒の沸点以下の保温を行う。When 2-chloro-6-methylaminopyridine is supplied as a solution and a solid precipitates at room temperature, it is kept at a temperature above its dissolution temperature and below the boiling point of the organic solvent used.
２−クロロ−６−メチルアミノピリジンを濃縮液を加熱
溶解させ、反応器へ供給する場合は、７０℃〜１００℃
の保温を行い、メタノールを添加する場合で、常温で固
体が析出する場合は、２−クロロ−６−メチルアミノピ
リジンの濃度により異なるが、通常６０℃以下で保温す
る。When dissolving 2-chloro-6-methylaminopyridine by heating the concentrated solution and supplying it to the reactor, the temperature is 70°C to 100°C.
If methanol is added and a solid precipitates at room temperature, the temperature is usually kept at 60° C. or lower, although this varies depending on the concentration of 2-chloro-6-methylaminopyridine.
２−クロロ−６−メチルアミノピリジンを供給するに際
して、供給時の反応器内温度は反応が進行する温度以上
であれば可能でであるが、好ましくは８０℃〜１６０’
Ｃでさらに好ましくは１００℃〜１５０℃である。When supplying 2-chloro-6-methylaminopyridine, the temperature within the reactor at the time of supply may be at least the temperature at which the reaction proceeds, but is preferably 80°C to 160°C.
C is more preferably 100°C to 150°C.
２−クロロ−６−メチルアミノピリジンの供給速度は、
反応温度の制御可能な速度であれば良く通常０．５〜８
．０時間である。The feed rate of 2-chloro-6-methylaminopyridine is
The speed may be as long as the reaction temperature can be controlled, usually 0.5 to 8.
．． It is 0 hours.
２−クロロ−６−メチルアミノピリジン供給終了後の熟
成は、必要に応じて１３０〜１６０”Ｃ１好ましくは１
３０〜１５０℃の範囲で２〜８時間熟成を行う。Aging after completion of supply of 2-chloro-6-methylaminopyridine may be carried out as necessary at 130 to 160" C1, preferably 1
Aging is performed for 2 to 8 hours at a temperature of 30 to 150°C.
反応終了後、冷却の後、水を添加、次いてメタノール並
びに有機溶媒を回収の後、有機溶媒で抽出、濃縮、蒸留
することにより、目的物２−メトキシ−６−メチルアミ
ノピリジンを得る。After completion of the reaction, after cooling, water is added, and methanol and organic solvent are recovered, followed by extraction with an organic solvent, concentration, and distillation to obtain the target product, 2-methoxy-6-methylaminopyridine.
〈発明の効果〉
本発明の方法を用いることにより反応温度の制御が容易
で、従来法と比較して内圧が低くより安全な工業的製造
法が確立された。<Effects of the Invention> By using the method of the present invention, a safer industrial production method was established in which the reaction temperature can be easily controlled and the internal pressure is lower than that of conventional methods.
しかも、２．６−ジクロロピリジンを原料とし、一連の
操作で、中間体２−クロロ−６−メチルアミノピリジン
を精製することなく２−メトキン−６−メチルアミノピ
リジンを得ることが可能となった。Moreover, using 2,6-dichloropyridine as a raw material, it became possible to obtain 2-methquine-6-methylaminopyridine through a series of operations without purifying the intermediate 2-chloro-6-methylaminopyridine. .
〈実施例〉
以下、実施例により本発明を具体的に説明するか本発明
はこれら実施例のみに限定されるものではない。<Examples> Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited only to these Examples.
〔実施例１〕
高圧圧入ポンプを供えた攪拌機付き５ｇの５ＵＳ３１６
製オートクレーブに２，６−ジクロロピリジン１３５０
ｇを仕込み、攪拌しながら加熱し１３０℃とした後、こ
れに４０％メチルアミン水溶液２１２５ｇ ＜メチルア
ミン含有量８５０ｇ）を高圧圧入ポンプで２時間かけて
供給、さらに同温度で２時間熟成を行った。供給中、熟
成中をとおして反応器内の最高圧力は６．３ｋｇ／α・
Ｇであった。[Example 1] 5g of 5US316 with a stirrer equipped with a high-pressure injection pump
2,6-dichloropyridine 1350 in a manufactured autoclave
After heating to 130°C with stirring, 2125 g of a 40% methylamine aqueous solution (methylamine content: 850 g) was fed to this over 2 hours using a high-pressure injection pump, and the mixture was further aged at the same temperature for 2 hours. Ta. The maximum pressure inside the reactor during feeding and aging was 6.3 kg/α・
It was G.
次いで、６０℃まで冷却の後、余剰のメチルアミンを除
去、さらに４８％水酸化ナトリウム水溶液を８４０ｇ添
加し、反応器内容物を１０ＣＩ”Ｃまで加熱することに
より、系内よリメチルアミンを除去した。Next, after cooling to 60° C., excess methylamine was removed, 840 g of 48% aqueous sodium hydroxide solution was added, and the contents of the reactor were heated to 10 CI″C to remove remethylamine from the system.
メチルアミン除去後、６０℃まで冷却し、反応器より抜
き出し、１０１の分液ロートに移し、ベンゼン１４００
ｇを添加、抽出、分液の後、２−クロロ−６−メチルア
ミノピリジンのベンゼン溶液２６５０ｇを得た。ガスク
ロマトグラフィーで分析の結果、該溶液中に２−クロロ
−６−メチルアミノピリジンは１２３５ｇ含有されてい
た。After removing methylamine, it was cooled to 60°C, extracted from the reactor, transferred to a 101 separatory funnel, and mixed with benzene 1400°C.
After addition of 2,650 g of a benzene solution of 2-chloro-6-methylaminopyridine, 2,650 g of a benzene solution of 2-chloro-6-methylaminopyridine was obtained. As a result of gas chromatography analysis, the solution contained 1235 g of 2-chloro-6-methylaminopyridine.
得られた２−クロロ−６−メチルアミノピリジンの反応
液を、５ｇの蒸留装置で内温７６〜１００℃に加熱する
ことにより、ベンゼンを留去し、２−クロロ−６−メチ
ルアミノピリジン１２３２ｇを含有する濃縮液１２４０
ｇとした後、５０℃まで冷却の後、これにメタノール７
３５ｇを添加した。The resulting reaction solution of 2-chloro-6-methylaminopyridine was heated to an internal temperature of 76 to 100°C using a 5g distillation apparatus to distill off benzene, yielding 1232g of 2-chloro-6-methylaminopyridine. Concentrated liquid 1240 containing
g, cooled to 50°C, and added methanol 7.
35g was added.
一方向じオートクレーブに、水酸化ナトリウム６９１ｇ
並びにメタノール６５０ｇを仕込んた後、攪拌しながら
１４５℃まで加熱、これに、前記２クロロ−６−メチル
アミノピリジンの溶液を、５０℃に保温した状態で、圧
入ポンプで１時間かけて供給の後、さらに同温度で２時
間熟成を行った。In a one-way autoclave, 691 g of sodium hydroxide.
After charging 650 g of methanol, it was heated to 145°C with stirring, and the solution of 2chloro-6-methylaminopyridine was fed to this over 1 hour using a press pump while keeping the temperature at 50°C. , and further aged for 2 hours at the same temperature.
供給中、熟成中の反応器内最高圧力は６． ５ｋｇ／■
・Ｇてあった。The maximum pressure inside the reactor during feeding and aging is 6. 5kg/■
・There was a G.
反応終了後、６０℃まで冷却の後、水２０００ｇを添加
、次いで加熱することにより余剰のメタノールを留去、
さらに四塩化炭素各５００ｍ１で４回抽出し、２−メト
キシル６−メチルアミノピリジンの溶液を得た。After the reaction was completed, after cooling to 60°C, 2000 g of water was added, and excess methanol was distilled off by heating.
Further, the mixture was extracted four times with 500 ml each of carbon tetrachloride to obtain a solution of 2-methoxyl 6-methylaminopyridine.
ガスクロマトグラフィーで分析の結果、２−メトキシ−
６−メチルアミノピリジン生成量は１０６２ｇで、６−
ジクロロピリジン基準収率８４゜２％であった。As a result of gas chromatography analysis, 2-methoxy-
The amount of 6-methylaminopyridine produced was 1062g, and 6-methylaminopyridine was
The yield based on dichloropyridine was 84.2%.
〔実施例２〜５〕
実施例１と同じ反応装置並びに操作で、表１中に示した
条件下反応を行った。[Examples 2 to 5] Using the same reaction apparatus and operation as in Example 1, reactions were carried out under the conditions shown in Table 1.
結果を表１中に示した。The results are shown in Table 1.
なお、反応器内最高圧力については、各実施例あわせて
、第一工程については、９．５ ｋｇ ／ ｃｍ・Ｇ以
下で、第二工程については７．０ｋｇ／ｃＩＩＩ−Ｇ以
下であった。The maximum pressure inside the reactor was 9.5 kg/cm·G or less for the first step and 7.0 kg/cIII-G or less for the second step in all Examples.
実施例１と同じ反応装置に、２，６−ジクロロピリジン
１３５０ｇ並びに４０％メチルアミン２１２５ｇ仕込み
反応を行った。Into the same reaction apparatus as in Example 1, 1350 g of 2,6-dichloropyridine and 2125 g of 40% methylamine were charged and a reaction was carried out.
反応は１３０℃で４時間行う予定であったが、反応熱の
ため内部温度が１４０℃まで上昇、また反応温度の上昇
に供ない、圧力か１３．０ｋｇ／ｃｍ・Ｇまで上昇した
。The reaction was scheduled to be carried out at 130° C. for 4 hours, but the internal temperature rose to 140° C. due to the reaction heat, and the pressure rose to 13.0 kg/cm·G due to the rise in reaction temperature.
反応終了後、実施例１と同量の水酸化ナトリウム水溶液
を添加、メチルアミンを留去、さらに、ベンゼンで抽出
、濃縮することにより２−クロロ−６−メチルアミンピ
リジン１２４０ｇを含有する濃縮液１２４３ｇを得た。After the reaction was completed, the same amount of sodium hydroxide aqueous solution as in Example 1 was added, methylamine was distilled off, and further extracted with benzene and concentrated to obtain 1243 g of a concentrated solution containing 1240 g of 2-chloro-6-methylaminepyridine. I got it.
次いで、濃縮液１２４３ｇ、水酸化ナトリウム６９１ｇ
並びにメタノール１３８５ｇをオートクレーブに仕込み
、加熱反応を行った。Next, 1243 g of concentrated liquid, 691 g of sodium hydroxide
In addition, 1385 g of methanol was charged into an autoclave, and a heating reaction was carried out.
反応は１４５℃で３時間行う予定であったが、反応熱の
ため内部温度が１５５℃まで上昇、また反応温度の上昇
に供ない、圧力が１１．０ｋｇ／ａｍ・Ｇまで上昇した
。The reaction was scheduled to be carried out at 145° C. for 3 hours, but the internal temperature rose to 155° C. due to the reaction heat, and the pressure rose to 11.0 kg/am·G as the reaction temperature rose.
反応終了後同様の操作を行い、２−メトキシ−６−メチ
ルアミノピリジン溶液を得、ガスクロマトグラフィーで
分析の結果、２，６−ジクロロピリジン基準収率で８３
．５％であった。After the completion of the reaction, the same operation was performed to obtain a 2-methoxy-6-methylaminopyridine solution, and as a result of gas chromatography analysis, the standard yield of 2,6-dichloropyridine was 83.
．． It was 5%.
Claims (2)
ン水溶液を供給し反応させた後、水酸化ナトリウム水溶
液を添加し、メチルアミンを回収、次いで有機溶媒で抽
出することにより２−クロロ−６−メチルアミノピリジ
ンの有機溶媒溶液を得、さらに引き続き、加熱した、メ
タノール並びに水酸化ナトリウム混合物に２−クロロ−
６−メチルアミノピリジンの有機溶媒溶液またはその濃
縮液、或いは溶液または濃縮液にメタノールを添加した
ものを供給し反応させることを特徴とする２−メトキシ
−６−メチルアミノピリジンの製造法。(1) After supplying a methylamine aqueous solution to heated 2,6-dichloropyridine and reacting it, adding a sodium hydroxide aqueous solution to recover methylamine, and then extracting it with an organic solvent to 2-chloro-6- A solution of methylaminopyridine in an organic solvent was obtained and subsequently dissolved in a heated mixture of methanol and sodium hydroxide with 2-chloro-
A method for producing 2-methoxy-6-methylaminopyridine, which comprises supplying and reacting a solution of 6-methylaminopyridine in an organic solvent, a concentrate thereof, or a solution or concentrate to which methanol has been added.
炭化水素、脂肪族炭化水素またはハロゲン化炭化水素で
あることを特徴とする製造法。(2) A manufacturing method characterized in that the organic solvent used in claim (1) is an aromatic hydrocarbon, an aliphatic hydrocarbon, or a halogenated hydrocarbon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18728390A JPH0477470A (en) | 1990-07-17 | 1990-07-17 | Production of 2-methoxy-6-methylaminopyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18728390A JPH0477470A (en) | 1990-07-17 | 1990-07-17 | Production of 2-methoxy-6-methylaminopyridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0477470A true JPH0477470A (en) | 1992-03-11 |
Family
ID=16203289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18728390A Pending JPH0477470A (en) | 1990-07-17 | 1990-07-17 | Production of 2-methoxy-6-methylaminopyridine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0477470A (en) |
-
1990
- 1990-07-17 JP JP18728390A patent/JPH0477470A/en active Pending
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