JPH03223279A - Production of n-substituted phthalimide - Google Patents
Production of n-substituted phthalimideInfo
- Publication number
- JPH03223279A JPH03223279A JP16129390A JP16129390A JPH03223279A JP H03223279 A JPH03223279 A JP H03223279A JP 16129390 A JP16129390 A JP 16129390A JP 16129390 A JP16129390 A JP 16129390A JP H03223279 A JPH03223279 A JP H03223279A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- phthalimide
- organic solvent
- compound
- general formula
- 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
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- -1 alkali metal salt Chemical class 0.000 claims abstract description 12
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 5
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 6
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical group [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 6
- 239000003518 caustics Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004436 sodium atom Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 6
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002635 aromatic organic solvent Substances 0.000 abstract description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 229910052700 potassium Inorganic materials 0.000 abstract description 2
- 239000008096 xylene Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 16
- 238000000034 method Methods 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 150000003956 methylamines Chemical class 0.000 description 3
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- SKCNYHLTRZIINA-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)pyridine Chemical compound ClCC1=CC=C(Cl)N=C1 SKCNYHLTRZIINA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VRMUIVKEHJSADG-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=CN=C(Cl)S1 VRMUIVKEHJSADG-UHFFFAOYSA-N 0.000 description 1
- 238000005642 Gabriel synthesis reaction Methods 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- VJGNLOIQCWLBJR-UHFFFAOYSA-M benzyl(tributyl)azanium;chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 VJGNLOIQCWLBJR-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は一般式
を示す。）で表わされる、Ｎ−置換フタルイミドの有利
な製造方法に関するものであり、本発明に係る化合物（
ＩＩＩ）を加水分解することにより、医薬及び農薬の中
間体として用いられる一数式ＡＣＨ，ＮＨ，で表わされ
るメチルアミン類を得る事ができ、化合物（Ｉ［Ｉ）は
きわめて有用な化合物である。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention presents a general formula. ), which relates to an advantageous process for the preparation of N-substituted phthalimides, represented by the compound according to the invention (
By hydrolyzing III), methylamines represented by the formula ACH, NH, which are used as intermediates for pharmaceuticals and agricultural chemicals, can be obtained, and compound (I[I) is an extremely useful compound.
フタルイミドのアルカリ金属塩とハロゲン化アルキルと
の反応による、Ｎ−置換フタルイミドの合成法は、−収
約にＧａｂｒｉｅｌ 合成法として知られており、Ｎ
、Ｎ−ジメチルホルムアミド（以下ＤＭＦという。）を
反応溶剤して用いる方法（ＪＡＣ３，７２，２７８６（
１９５０）） 、無溶媒にて１２０〜１３０℃で反応さ
せる方法（Ａｎｎａｌｅｎ ｄｅｒ ｃｈｅｍｉｅ。The synthesis of N-substituted phthalimides by reaction of an alkali metal salt of phthalimide with an alkyl halide is known as the Gabriel synthesis method for
, a method using N-dimethylformamide (hereinafter referred to as DMF) as a reaction solvent (JAC3,72,2786 (
1950)), a method of reacting at 120 to 130°C without a solvent (Annalen der chemie).
虱６１ （１９５７））等が知られている。61 (1957)) are known.
本発明で製造される化合物（Ｉｎ）も、上記方法で好収
率で得る事ができ、ＤＭＦを反応溶剤に用いる方法につ
いては西独公開特許３７２７１２６号に記載がある。The compound (In) produced in the present invention can also be obtained in good yield by the above method, and a method using DMF as a reaction solvent is described in West German Published Patent Application No. 3727126.
しかしながら、ＤＭＦを反応溶剤に用いる方法では、比
較的高価な無水のＤＭＦを回収するのにコストか掛り経
済的に好ましくなく、また無溶媒の方法では後処理か煩
雑となる。更に、両方法とも原料に比較的高価な無水の
フタルイミドカリウムを必要とし、経済的に好ましい方
法とはいえない。However, the method using DMF as a reaction solvent is economically unfavorable because it costs money to recover relatively expensive anhydrous DMF, and the method using no solvent requires complicated post-treatment. Furthermore, both methods require relatively expensive anhydrous potassium phthalimide as a raw material, and are not economically preferred methods.
そこで、本発明者は、これらの欠点を改良する目的で、
鋭意検討を重ねた結果、安価なフタルイミドを出発原料
として、安価な有機溶剤中、四級アンモニウム塩を触媒
として、穏和な反応条件下に、安易かつ好収率で化合物
（ｎＩ）が製造できることを見出した。Therefore, in order to improve these drawbacks, the present inventors
As a result of extensive research, we found that compound (nI) can be produced easily and in good yield under mild reaction conditions using inexpensive phthalimide as a starting material in an inexpensive organic solvent and using a quaternary ammonium salt as a catalyst. I found it.
即ち、本発明は（１）−数式（Ｉ） （式中、Ｍはナトリウム原子又はカリウム原子を示す。That is, the present invention provides (1)-formula (I) (In the formula, M represents a sodium atom or a potassium atom.
）で表わされるフタルイミドのアルカリ金属塩と
一般式
％式％（）
（式中、Ａは前記と同じ意味を示し、Ｘは塩素原子又は
臭素原子を示す。）で表わされる化合物を、水難溶性有
機溶剤中、四級アンモニウム塩を触媒として反応させる
事を特徴とする特許
で表わされるＮ−置換フタルイミドの製造方法、（２）
−数式
で表わされる化合物の製造方法において、（ａ） フ
タルイミドを、水難溶性有機溶剤中、低級アルコールの
存在下に苛性アルカリと反応させながら、副生ずる水を
低級アルコールと共に共沸脱水して
一般式
で表わされるフタルイミドのアルカリ金属塩を製造する
工程
（ｂ） （ａ）工程で得た化合物（Ｉ）を、
水難溶性有
機溶媒中、四級アンモニウム塩を触媒として、前記化合
物（Ｉ［）と反応させることにより、前記化合物（ＩＩ
Ｉ）を製造する工程
以上２工程からなることを特徴とする化合物（ＩＩＩ）
の製造方法である。) and a compound represented by the general formula % (in the formula, A has the same meaning as above, and X represents a chlorine atom or a bromine atom), a poorly water-soluble organic A method for producing N-substituted phthalimide described in a patent, characterized in that the reaction is carried out in a solvent using a quaternary ammonium salt as a catalyst, (2)
- In a method for producing a compound represented by the formula, (a) phthalimide is reacted with a caustic alkali in a sparingly water-soluble organic solvent in the presence of a lower alcohol, and by-produced water is azeotropically dehydrated with the lower alcohol to obtain the compound represented by the general formula Step (b) of producing an alkali metal salt of phthalimide represented by: Reacting the compound (I) obtained in step (a) with the compound (I[) in a sparingly water-soluble organic solvent using a quaternary ammonium salt as a catalyst. The compound (II
Compound (III) characterized in that it consists of two steps above the step of producing I)
This is a manufacturing method.
化合物（Ｉ）の製造において、苛性アルカリとしては、
苛性ソーダ又は苛性カリが使用でき、フタルイミドに対
して等モル使用すれば良い。有機溶剤としては、ベンゼ
ン、トルエン、キシレン等の芳香族系有機溶剤、四塩化
炭素等の塩素系有機溶剤、又は、メチルイソブチルケト
ン等のケトン系溶剤等の水難溶性有機溶剤が挙げられる
が、好ましくは芳香族系有機溶剤が、特にトルエンが好
ましい。In the production of compound (I), as the caustic alkali,
Caustic soda or caustic potash can be used, and it is sufficient to use equimolar amounts to phthalimide. Examples of the organic solvent include aromatic organic solvents such as benzene, toluene, and xylene, chlorinated organic solvents such as carbon tetrachloride, and poorly water-soluble organic solvents such as ketone solvents such as methyl isobutyl ketone. is preferably an aromatic organic solvent, particularly preferably toluene.
低級アルコールとしてはメチルアルコール、エチルアル
コール等のアルコールが使用でき、経済的には安価なメ
チルアルコールが好ましく、又こうしたアルコールが存
在する事で、フタルイミドと苛性アルカリとの反応をス
ムーズにし、さらに副生ずる水を共沸脱水にて除去する
際に、析出した化合物（Ｉ）が反応器壁にスケーリング
する現象を防止できる。As the lower alcohol, alcohols such as methyl alcohol and ethyl alcohol can be used, and economically inexpensive methyl alcohol is preferable, and the presence of such alcohol smoothes the reaction between phthalimide and caustic alkali, and further reduces by-products. When water is removed by azeotropic dehydration, it is possible to prevent the precipitated compound (I) from scaling on the walls of the reactor.
化合物（ＩＩ［）製造において、四級アンモニウム塩を
加えない場合、反応はほとんど進行せず、四級アンモニ
ウム塩を加えて、初めて反応はスムーズに進行し、好収
率で目的物が得られる。本反応に用いられる四級アンモ
ニウム塩としては、トリオクチルメチルアンモニウムク
ロリド、ベンジルトリブチルアンモニウムクロリド、ベ
ンジルトリエチルアンモニウムクロリド等、通常市販さ
れている四級アンモニウム塩が使用でき、特にトリオク
チルメチルアンモニウムクロリドが好ましく、化合物（
ｎ）に対し、１．０〜５．０モル％の使用で充分目的を
達成できる。化合物（ＩＩ）に対してフタルイミドは、
１．０〜１．１モル使用すればよく、有機溶剤としては
、化合物（１）の製造に使用した溶剤をそのまま使用す
ればよい。反応温度は、使用する有機溶剤によっても異
なるが、３０〜１３０°Ｃ１特に４５〜８０℃が好まし
い。反応温度がこれより低いと反応速度が遅くなり、こ
れ以上高いと化合物（ＩＩ）が分解し、収率が低下する
場合がある。In the production of compound (II[), if a quaternary ammonium salt is not added, the reaction hardly proceeds, and only when a quaternary ammonium salt is added, the reaction proceeds smoothly and the desired product can be obtained in a good yield. As the quaternary ammonium salt used in this reaction, commercially available quaternary ammonium salts such as trioctylmethylammonium chloride, benzyltributylammonium chloride, and benzyltriethylammonium chloride can be used, and trioctylmethylammonium chloride is particularly preferred. ,Compound(
The purpose can be sufficiently achieved by using 1.0 to 5.0 mol % of the amount of n). For compound (II), phthalimide is
What is necessary is to use 1.0 to 1.1 mol, and as the organic solvent, the solvent used in the production of compound (1) may be used as it is. The reaction temperature varies depending on the organic solvent used, but is preferably 30 to 130°C, particularly 45 to 80°C. If the reaction temperature is lower than this, the reaction rate will be slow, and if it is higher than this, compound (II) may decompose and the yield may decrease.
反応終了後、得られた化合物（ＤＩ）の溶液を水洗し、
濃縮、再結晶等通常の処理をすることにより、目的物を
取得することができる。又、得られた化合物（ＩＩＩ）
の溶液から化合物（ＩＩＩ）を取り出すことなく、アリ
カリ加水分解、引き続き酸加水分解に付すことにより、
容易かつ好収率で中間体として有用な一数式Ａ−ＣＨ，
ＮＨ，で表わされるメチルアミン類を取得することもで
きる。After completion of the reaction, the obtained solution of compound (DI) was washed with water,
The target product can be obtained by performing usual treatments such as concentration and recrystallization. Moreover, the obtained compound (III)
By subjecting compound (III) to alkali hydrolysis and then acid hydrolysis without removing it from the solution,
A formula A-CH useful as an intermediate with ease and good yield,
Methylamines represented by NH, can also be obtained.
以下に示す実施例は、本発明を説明するものであって、
何らこれに限定されるものではない。The examples given below illustrate the invention:
It is not limited to this in any way.
実施例１
化合物（ＩＩＩ−ａ）
フタルイミド１５．４５ｇ （０，１０５ｍｏｌ）をト
ルエン２４０Ｉｎｌ中に加え、攪拌下９６％苛性カリ６
．１４ ｇ （０，１０５ｍｏｌ）及びメタノール２４
．０ ｇを加え、常圧下にトルエンと共にメタノール及
び副生ずる水を留去した。（留去量１５０ｄ）次に、７
０℃迄冷却し、トリオクチルメチルアンモニウムクロリ
ド０．８１ ｇ （０，００２ｍｏｌ）を加え、更に２
−クロロ−５−（クロロメチル）ピリジン１６、２０
ｇ （０，１ｍｏｌ）を加え、７０〜７５℃で２時間攪
拌した。反応終了後、５０℃迄冷却し、水８０ｄで水洗
して副生じた塩化カリウムを除去し、分岐して得たトル
エン層を濃縮して目的物Ｎ〔（２−クロロピリジン−５
−イル）メチル〕フタルイミドの粗結晶２８．０ ｇを
得た。Example 1 Compound (III-a) 15.45 g (0.105 mol) of phthalimide was added to 240 Inl of toluene, and 96% caustic potassium 6 was added under stirring.
．． 14 g (0,105 mol) and methanol 24
．． 0 g was added, and methanol and by-produced water were distilled off together with toluene under normal pressure. (Distilled amount: 150 d) Next, 7
Cool to 0°C, add 0.81 g (0,002 mol) of trioctylmethylammonium chloride, and add 2
-Chloro-5-(chloromethyl)pyridine 16, 20
g (0.1 mol) was added thereto, and the mixture was stirred at 70 to 75°C for 2 hours. After the reaction was completed, it was cooled to 50°C, washed with 80 d of water to remove by-produced potassium chloride, and the toluene layer obtained by branching was concentrated to obtain the target product N [(2-chloropyridine-5
28.0 g of crude crystals of -yl)methyl]phthalimide were obtained.
得られた粗結晶をエタノールより再結晶して、ｍ。The obtained crude crystals were recrystallized from ethanol to obtain m.
ｐ、１３９〜１４０℃の白色結晶２６．６ ｇを得た。26.6 g of white crystals with a temperature of 139-140°C were obtained.
収率９７，６％
ＮＭＲスペクトル（ＣＤＣｊ２＋ ）δｐｐｍ；４．８
３（２Ｈ１ｓ） ７．２７〜８．５０ （３Ｈ，ｍ）
７．７２〜７．７７ （４Ｈ，ｍ）
実施例２
化合物（ＩＩＩ−ｂ）
フタルイミドカリ１９．４ ｇ （０，１０５ｍｏｌ）
をトルエンｌ００１ｄ中に懸濁させ、トリオクチルメチ
ルアンモニウムクロリド０．８ ｇ （０，００２ｍｏ
ｌ）及び２−クロロ−５−（クロロメチル）チアゾール
１６．８ ｇ （０，１１１１０１）を加え、攪拌下に
７０〜７５℃で２．５時間加熱した。反応溶液を室温迄
冷却し、水４０−を加え未反応のフタルイミドカリと、
反応で生成した塩化カリウムを除去した。分岐して得た
トルエン層を減圧上濃縮乾固し目的物Ｎ（２−クロロ−
５−チアゾリルメチル）フタルイミドの粗結晶２８ｇを
得た。得られた粗結晶をエタノールより再結晶しｍｐ、
ｌ ０９−１１０．５°Ｃの白色結晶２５．１ ｇを得
た。収率９０，１％参考例１
２−クロロ−５−（アミノメチル）ピリジンフタルイミ
ド１５．４５ｇ （０，１０５ｍｏｌ）をトルエン２４
〇−中に加え、攪拌下９６％苛性カリ６、１４ｇ（０、
ｌ Ｏ５ｍｏｌ）及びメタノール２４．０ ｇを加え、
常圧下にトルエンと共にメタノール及び副生ずる水を留
去した。（留去量１５０ｄ）次に７０℃迄冷却し、トリ
オクチルメチルアンモニウムクロリド０．６１ ｇ （
０，００１５ｍｏｌ）を加え、更に２−クロロ−５−（
クロロメチル）ピリジン１６、２０ ｇ （０，Ｉｎ＋
ｏｌ）を加え、７０〜７５℃で３時間攪拌した。反応終
了後、水１０〇−及び２５％苛性ソーダ水溶液１９．２
ｇ （０，１２ｍｏｌ）を加え、７０〜７５℃で１時
間攪拌し、アルカリ加水分解した。Yield 97.6% NMR spectrum (CDCj2+) δppm; 4.8
3 (2H1s) 7.27~8.50 (3H, m)
7.72-7.77 (4H, m) Example 2 Compound (III-b) Potassium phthalimide 19.4 g (0,105 mol)
was suspended in toluene 1001d and 0.8 g trioctylmethylammonium chloride (0,002 mo
1) and 16.8 g (0,111101) of 2-chloro-5-(chloromethyl)thiazole were added and heated at 70-75° C. for 2.5 hours with stirring. The reaction solution was cooled to room temperature, and 40% of water was added to remove unreacted potassium phthalimide.
Potassium chloride produced in the reaction was removed. The toluene layer obtained by branching was concentrated to dryness under reduced pressure to obtain the target product N (2-chloro-
28 g of crude crystals of 5-thiazolylmethyl)phthalimide were obtained. The obtained crude crystals were recrystallized from ethanol,
25.1 g of white crystals with a temperature of 09-110.5°C were obtained. Yield 90.1% Reference Example 1 15.45 g (0.105 mol) of 2-chloro-5-(aminomethyl)pyridinephthalimide was dissolved in 24 g of toluene.
〇- Add 6.14 g (0,
1 O5 mol) and methanol 24.0 g,
Methanol and by-product water were distilled off together with toluene under normal pressure. (Distilled amount: 150 d) Next, it was cooled to 70°C, and 0.61 g of trioctylmethylammonium chloride (
0,0015 mol) was added, and further 2-chloro-5-(
chloromethyl)pyridine 16,20 g (0,In+
ol) was added and stirred at 70 to 75°C for 3 hours. After the reaction, add 100% water and 19.2% 25% caustic soda aqueous solution.
g (0.12 mol) was added thereto, and the mixture was stirred at 70 to 75°C for 1 hour to perform alkaline hydrolysis.
ついで熱時分液し、得られた水層を、攪拌下１０％塩酸
水溶液８７．５ ｇ （０，２４ｍｏｌ）中に内温を７
０〜７５℃に保ちながら２０分かけて滴下した。Then, the aqueous layer obtained was heated to 87.5 g (0.24 mol) of a 10% aqueous hydrochloric acid solution at an internal temperature of 7.
The mixture was added dropwise over 20 minutes while maintaining the temperature at 0 to 75°C.
その後、９０〜９５℃にて１時間１５分攪拌し、酸加水
分解した。Thereafter, the mixture was stirred at 90 to 95°C for 1 hour and 15 minutes to perform acid hydrolysis.
酸加水分解終了後、トルエン５０ｙｄを加えて洗浄し、
熱時分液して得られた水層を室温迄冷却し、食塩２６．
０ ｇを加えた後、５０％苛性ソーダ水溶液２６．０
ｇを加えてｐＨを１２以上とし、クロロホルムで目的物
を抽出した。得られたクロロホルム溶液を硫酸マグネシ
ウムで乾燥後濃縮し、目的物粗ｏｉ１ １２．７１ｇ（
冷却すると固化した。）を得た。After acid hydrolysis, add 50 yd of toluene and wash.
The aqueous layer obtained by thermal separation was cooled to room temperature, and 26.
After adding 0 g, 50% caustic soda aqueous solution 26.0
g was added to adjust the pH to 12 or higher, and the target product was extracted with chloroform. The obtained chloroform solution was dried over magnesium sulfate and then concentrated to obtain 12.71 g of the target product crude oil1 (
It solidified on cooling. ) was obtained.
得られた粗ｏｉｌを減圧蒸留に付し、１ｍ＋ｎ）１ｇ９
２〜９４℃の留分１２．５２ｇ（冷却すると固化。ｍ。The obtained crude oil was subjected to vacuum distillation to obtain 1 m+n) 1 g9
12.52 g of fraction between 2 and 94°C (solidifies on cooling. m.
ｐ、２５〜２６℃）を得た。収率８７，８％ＮＭＲスペ
クトル（ＣＤ＋１．）δｐｐｍ；１．４９ （２Ｈ，５
ｂｒｏａｄ）３．９０ （２ＨＸｓ）７゜２９〜８．３
４ （３Ｈ，ｍ）
又、酸加水分解後の洗浄トルエン層を濃縮乾固すること
により、１．４４ ｇの化合物（ＩＩ−ａ）が回収され
た。回収率５゜３％
〔発明の効果〕
本発明による化合物（Ｉ［Ｉ）の製造方法は、従来の方
法に比べ、安価に、穏和な条件下に好収率で目的物が得
られ、更に反応の後処理も非常に安易であること等、有
利な工業的製法である。p, 25-26°C). Yield 87.8% NMR spectrum (CD+1.) δppm; 1.49 (2H,5
broad) 3.90 (2HXs) 7°29~8.3
4 (3H, m) Furthermore, 1.44 g of compound (II-a) was recovered by concentrating and drying the washed toluene layer after acid hydrolysis. Recovery rate: 5.3% [Effects of the Invention] Compared to conventional methods, the method for producing compound (I[I) of the present invention can obtain the desired product at a low cost and in a good yield under mild conditions, and furthermore, This is an advantageous industrial production method because post-treatment of the reaction is also very easy.
更に参考例からも明らかなように、本発明の製造方法に
より製造された化合物（Ｉ［［）を単離することなく、
加水分解し、−数式Ａ Ｃ８２ＮＨＫで表わされるメ
チルアミン類を製造することも可能である。Furthermore, as is clear from the reference examples, without isolating the compound (I[[) produced by the production method of the present invention,
It is also possible to produce methylamines of the formula AC82NHK by hydrolysis.
Claims (1)
数式、化学式、表等があります▼を、Ｘは塩素原子又は
臭素原子を示す。）で表わされる化合物を、水難溶性有
機溶剤中、四級アンモニウム塩を触媒として反応させる
事を特徴とする一般式 ▲数式、化学式、表等があります▼（III） （式中、Ａは前記と同じ意味を示す。）で表わされるＮ
−置換フタルイミドの製造方法。（２）一般式 ▲数式、化学式、表等があります▼（III） （式中、Ａは前記と同じ意味を示す。）で表わされる化
合物の製造方法において、 （ａ）フタルイミドを、水難溶性有機溶剤中、低級アル
コールの存在下に苛性アルカリと反応させながら、副生
する水を低級アルコールと共に共沸脱水して 一般式 ▲数式、化学式、表等があります▼（ I ） で表わされるフタルイミドのアルカリ金属塩を製造する
工程 （ｂ）（ａ）工程で得た化合物（ I ）を、水難溶性有
機溶媒中、四級アンモニウム塩を触媒として、一般式Ａ
−ＣＨ＿２Ｘ（式中、Ａ及びＸは前記と同じ意味を示す
。）で表わされる化合物と反応させることにより、 一般式 ▲数式、化学式、表等があります▼（III） （式中、Ａは前記と同じ意味を示す。）で表わされるＮ
−置換フタルイミドを製造する工程 以上２工程からなることを特徴とする一般式（III）で
表わされるＮ−置換フタルイミドの製造方法。 （３）四級アンモニウム塩がトリオクチルメチルアンモ
ニウムクロリドである特許請求の範囲第１項、又は第２
項に記載の製造方法。 （４）水難溶性有機溶剤がトルエンである特許請求の範
囲第１項、又は第２項に記載の製造方法。 （５）低級アルコールがメチルアルコールである特許請
求の範囲第２項に記載の製造方法。[Claims] (1) General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) (In the formula, M represents a sodium atom or a potassium atom) An alkali metal salt of phthalimide and the general formula A-CH_2X(II) (In the formula, A is a ▲ mathematical formula, chemical formula, table, etc. ▼ or ▲
There are mathematical formulas, chemical formulas, tables, etc. Where ▼ indicates a chlorine atom or a bromine atom. ) is reacted with a compound represented by the above formula in a sparingly water-soluble organic solvent using a quaternary ammonium salt as a catalyst ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) ) has the same meaning.
- A method for producing a substituted phthalimide. (2) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) (In the formula, A has the same meaning as above.) In the method for producing a compound represented by While reacting with a caustic alkali in the presence of a lower alcohol in a solvent, the by-produced water is azeotropically dehydrated with the lower alcohol to form an alkali of phthalimide represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) Step (b) of producing a metal salt: The compound (I) obtained in step (a) is mixed with the general formula A in a poorly water-soluble organic solvent using a quaternary ammonium salt as a catalyst.
By reacting with a compound represented by -CH_2X (wherein A and ) has the same meaning as N
A method for producing an N-substituted phthalimide represented by the general formula (III), which comprises two steps: - producing a substituted phthalimide. (3) Claim 1 or 2, wherein the quaternary ammonium salt is trioctylmethylammonium chloride.
The manufacturing method described in section. (4) The manufacturing method according to claim 1 or 2, wherein the poorly water-soluble organic solvent is toluene. (5) The manufacturing method according to claim 2, wherein the lower alcohol is methyl alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16129390A JPH03223279A (en) | 1989-12-27 | 1990-06-21 | Production of n-substituted phthalimide |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33623389 | 1989-12-27 | ||
| JP1-336233 | 1989-12-27 | ||
| JP16129390A JPH03223279A (en) | 1989-12-27 | 1990-06-21 | Production of n-substituted phthalimide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03223279A true JPH03223279A (en) | 1991-10-02 |
Family
ID=26487474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16129390A Pending JPH03223279A (en) | 1989-12-27 | 1990-06-21 | Production of n-substituted phthalimide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03223279A (en) |
-
1990
- 1990-06-21 JP JP16129390A patent/JPH03223279A/en active Pending
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