JP4538993B2 - Process for producing β-ketonitrile derivatives - Google Patents

Process for producing β-ketonitrile derivatives Download PDF

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Publication number
JP4538993B2
JP4538993B2 JP2001192455A JP2001192455A JP4538993B2 JP 4538993 B2 JP4538993 B2 JP 4538993B2 JP 2001192455 A JP2001192455 A JP 2001192455A JP 2001192455 A JP2001192455 A JP 2001192455A JP 4538993 B2 JP4538993 B2 JP 4538993B2
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group
atom
reaction
substituent
mol
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JP2003012630A (en
Inventor
明生 松下
清隆 吉井
雅良 大上
卓 中村
修二 山田
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Ube Corp
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Ube Industries Ltd
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Description

【0001】
【発明の属する技術分野】
本発明は、医薬・農薬等の合成原料として有用なβ-ケトニトリル誘導体の製法に関する。
【0002】
【従来の技術】
従来、β-ケトニトリル誘導体の製法としては、式(3)
【0003】
【化3】
【0004】
で示されるように、2-ベンゾイルプロピオンアルデヒドにヒドロキシルアミン塩酸塩を反応させて4-メチル-5-フェニルイソオキサゾールとした後、次いで、塩基で開環させることにより2-ベンゾイルプロピオニトリルを合成している(薬学雑誌、79,267(1959))。しかしながら、この方法では、一旦環化させた後に開環させるため、反応操作及び後処理が繁雑となる等、工業的な製法としては問題があった。
【0005】
【発明が解決しようとする課題】
本発明の課題は、即ち、上記問題点を解決し、β-ケトエノール誘導体から簡便な方法によりβ-ケトニトリル誘導体を製造する、工業的に好適なβ-ケトニトリル誘導体の製法を提供するものである。
【0006】
【課題を解決するための手段】
本発明の課題は、一般式(1)
【0007】
【化4】
【0008】
(式中、R及びRは、同一又は異なっていても良く、置換基を有していても良いメチル基、エチル基、プロピル基、ブチル基、フェニル基、ナフチル基、又はアントリル基である。なお、これらの基は各種異性体を含み、当該置換基としては、メトキシル基、エトキシル基、プロポキシル基、ブトキシル基、フッ素原子、塩素原子、臭素原子及びヨウ素原子からなる群より選ばれる少なくとも1つの置換基である。Mは、アルカリ金属原子、水素原子又は炭化水素基を示す。)で示されるβ−ケトエノール誘導体に、ヒドロキシルアミン−O−スルホン酸を反応させることを特徴とする、一般式(2)
【0009】
【化5】
【0010】
(式中、R1及びR2は、前記同義である。)
で示されるβ-ケトニトリル誘導体の製法によって解決される。
【0011】
【発明の実施の形態】
本発明の反応において、一般式(1)で示されるβ-ケトエノール誘導体のR1及びR2は、同一又は異なっていても良く、反応に関与しない基を示すが、特に、置換基を有していても良いアルキル基又はアリール基であり、具体的には、例えば、メチル基、エチル基、プロピル基、ブチル基等のアルキル基;フェニル基、ナフチル基、アントリル基等のアリール基が挙げられる。なお、これらの基は各種異性体を含む。
【0012】
前記の置換基としては、メトキシル基、エトキシル基、プロポキシル基、ブトキシル基等のアルコキシル基;フッ素原子、塩素原子、臭素原子、ヨウ素原子等のハロゲン原子が挙げられる。なお、置換基の数や位置は特に限定されない。
【0013】
一般式(1)において、Mは、アルカリ金属原子、水素原子又は炭化水素基を示すが、具体的には、例えば、リチウム原子、ナトリウム原子、カリウム原子等のアルカリ金属原子;水素原子;メチル基、エチル基、プロピル基、ブチル基等の炭化水素基(これらの炭化水素基は各種異性体を含む)が挙げられるが、好ましくはアルカリ金属原子である。
【0014】
なお、本発明の反応において使用されるβ-ケトエノール誘導体は、ケトン化合物とギ酸エステルから容易に合成出来る化合物である(例えば、J.Heterocyclic.Chem.,24,351(1987))。
【0015】
本発明の反応において使用されるヒドロキシルアミン-O-スルホン酸は、遊離のヒドロキシルアミン-O-スルホン酸(水和物も含む)だけでなく、その水溶液として使用しても良い。
【0016】
前記ヒドロキシルアミン-O-スルホン酸の使用量は、β-ケトエノール誘導体1molに対して、好ましくは0.5〜20mol、更に好ましくは0.8〜10molである。
【0017】
本発明の反応は、溶媒の存在下又は非存在下で行われる。使用される溶媒は反応に関与しないものならば特に限定されず、例えば、水;メタノール、エタノール、n-プロピルアルコール、イソプロピルアルコール、n-ブチルアルコール、イソブチルアルコール、t-ブチルアルコール等のアルコール類;N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド、N,N'-ジメチル-2-イミダゾリドン等のアミド類;アセトニトリル、プロピオニトリル、ベンゾニトリル等のニトリル類が挙げられるが、好ましくは水、アルコール類、水とアルコールの混合溶媒が使用される。なお、これらの溶媒は、単独又は二種以上を混合して使用しても良い。
【0018】
前記溶媒の使用量は、溶液の均一性や攪拌性により適宜調節するが、β-ケトエノール誘導体1gに対して、好ましくは0.1〜1000ml、更に好ましくは1〜100mlである。
【0019】
本発明の反応は、例えば、不活性ガスの雰囲気にて、β-ケトエノール誘導体、ヒドロキシルアミン-O-スルホン酸及び溶媒を混合して、攪拌する等の方法によって行われる。その際の反応温度は、好ましくは0〜200℃、更に好ましくは5〜100℃であり、反応圧力は特に制限されない。
【0020】
本発明の反応によって得られるβ-ケトニトリル誘導体は、反応終了後、例えば、中和、抽出、濃縮、濾過等の処理を行った後に、再結晶、晶析、蒸留、カラムクロマトグラフィー等のよる一般的な方法によって単離・精製される。
【0021】
【実施例】
次に、実施例を挙げて本発明を具体的に説明するが、本発明の範囲はこれらに限定されるものではない。
【0022】
参考例1(2-メチル-3-オキソブチルアルデヒドのナトリウム塩の合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積500mlのフラスコに、窒素雰囲気にて、ナトリウムメトキシド32.41g(0.60mol)、トルエン300ml及びエタノール48mlを加えた。次いで、反応液を0〜5℃に維持して攪拌しながら、2-ブタノン43.27g(0.60mol)及びギ酸エチル45.79g(0.62mol)の混合液をゆるやかに滴下し、同温度で2時間、更に室温まで昇温して15時間反応させた。反応終了後、濾過し、濾過物を乾燥して、無色粉末として2-メチル-3-オキソブチルアルデヒドのナトリウム塩53.76gを得た(単離収率:73%)。
2-メチル-3-オキソブチルアルデヒドのナトリウム塩の物性値は以下の通りであった。
【0023】
1H-NMR(DMSO-d6,δ(ppm));1.39(3H,s)、1.88(3H,s)、9.07(1H,s)
【0024】
実施例1(3-シアノ-2-ブタノンの合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積300mlのフラスコに、参考例1の方法と同様に合成した2-メチル-3-オキソブチルアルデヒドのナトリウム塩36.63g(0.30mol)及び水100mlを加えた。次いで、反応液を5〜10℃に維持して攪拌しながら、ヒドロキシルアミン-O-スルホン酸37.32g(0.33mol)を水60mlに溶解させた水溶液をゆるやかに滴下し、室温で6時間反応させた。反応終了後、酢酸エチル150mlで2回抽出した。有機層を取り出し、有機層をガスクロマトグラフィー(内部標準法)で分析したところ、3-シアノ-2-ブタノンが21.80g(反応収率:75%)生成していた。その後、有機層を無水硫酸マグネシウムで乾燥させた。濾過後、濾液を減圧下で濃縮し、無色液体として3-シアノ-2-ブタノン19.50gを得た(単離収率:67%)。
3-シアノ-2-ブタノンの物性値は以下の通りであった。
【0025】
1H-NMR(DMSO-d6,δ(ppm));1.50(3H,d)、2.38(3H,s)、3.60(1H,q)
【0026】
実施例2(3-シアノ-2-ブタノンの合成)
実施例1において、抽出溶媒を酢酸エチルから1,2-ジクロロエタンに変えたこと以外は、実施例1と同様に反応を行った。抽出した有機層(1,2-ジクロロエタン層)をガスクロマトグラフィー(内部標準法)により分析したところ、3-シアノ-2-ブタノンが22.10g(反応収率:76%)生成していた。
【0027】
参考例2(2-メチル-3-オキソブチルアルデヒドの合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積200mlのフラスコに、参考例1と同様な方法で合成した2-メチル-3-オキソブチルアルデヒドのナトリウム塩12.2g(0,10mol)及び水40mlを加えた。次いで、反応液を10℃に維持して攪拌しながら、濃塩酸8.3mlをゆるやかに滴下した。反応終了後、塩化メチレン50mlを加え、有機層を取り出し、無水硫酸マグネシウムで乾燥させた。濾過後、濾液を減圧下で濃縮し、無色粉末として2-メチル-3-オキソブチルアルデヒド7.0gを得た(単離収率:70%)。
2-メチル-3-オキソブチルアルデヒドの物性値は以下の通りであった。
【0028】
1H-NMR(CDCl3,δ(ppm));1.80(3H,d)、2.14(3H,s)、7.70〜7.80(1H,m)、14.65(1H,d)
【0029】
実施例3(3-シアノ-2-ブタノンの合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積300mlのフラスコに、参考例2の方法と同様に合成した2-メチル-3-オキソブチルアルデヒド30.10g(0.30mol)及び水100mlを加えた。次いで、反応液を5〜10℃に維持して攪拌しながら、ヒドロキシルアミン-O-スルホン酸37.32g(0.33mol)を水60mlに溶解させた水溶液をゆるやかに滴下し、室温で6時間反応させた。反応終了後、酢酸エチル150mlで2回抽出した。有機層を取り出し、有機層をガスクロマトグラフィー(内部標準法)で分析したところ、3-シアノ-2-ブタノンが19.80g(反応収率:67%)生成していた。
【0030】
参考例3(2-エチル-3-オキソブチルアルデヒドのナトリウム塩の合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積500mlのフラスコに、窒素雰囲気にて、ナトリウムメトキシド32.41g(0.60mol)、トルエン300ml及びエタノール48mlを加えた。次いで、反応液を0〜5℃に維持して攪拌しながら、2-ペンタノン51.68g(0.60mol)及びギ酸エチル45.79g(0.62mol)の混合液をゆるやかに滴下し、同温度で2時間、更に室温まで昇温して15時間反応させた。反応終了後、濾過し、濾過物を乾燥して、無色粉末として2-エチル-3-オキソブチルアルデヒドのナトリウム塩21.30gを得た(単離収率:26%)。
2-エチル-3-オキソブチルアルデヒドのナトリウム塩の物性値は以下の通りであった。
【0031】
1H-NMR(DMSO-d6,δ(ppm));0.72(3H,t)、1.87(3H,s)、2.02(2H,q)、9.00(1H,s)
【0032】
実施例4(3-シアノ-2-ペンタノンの合成)
攪拌装置、温度計及び滴下漏斗を備えた内容積300mlのフラスコに、参考例3の方法と同様に合成した2-エチル-3-オキソブチルアルデヒドのナトリウム塩40.83g(0.30mol)及び水100mlを加えた。次いで、反応液を5〜10℃に維持して攪拌しながら、ヒドロキシルアミン-O-スルホン酸37.32g(0.33mol)を水60mlに溶解させた水溶液をゆるやかに滴下し、室温で6時間反応させた。反応終了後、酢酸エチル200mlで2回抽出した。有機層を取り出し、有機層をガスクロマトグラフィー(内部標準法)で分析したところ、3-シアノ-2-ペンタノンが25.00g(反応収率:75%)生成していた。その後、有機層を無水硫酸マグネシウムで乾燥させた。濾過後、濾液を減圧下で濃縮し、無色液体として3-シアノ-2-ペンタノン24.30gを得た(単離収率:73%)。
3-シアノ-2-ペンタノンの物性値は以下の通りであった。
【0033】
1H-NMR(DMSO-d6,δ(ppm));0.97(3H,t)、1.95〜2.22(2H,m)、2.26(3H,s)、4.02〜4.12(1H,m)
【0034】
【発明の効果】
本発明により、β-ケトエノール誘導体から簡便な方法によりβ-ケトニトリル誘導体を製造する、工業的に好適なβ-ケトニトリル誘導体の製法を提供することが出来る。
[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a process for producing a β-ketonitrile derivative useful as a synthetic raw material for pharmaceuticals, agricultural chemicals and the like.
[0002]
[Prior art]
Conventionally, as a method for producing a β-ketonitrile derivative, the formula (3) is used.
[0003]
[Chemical 3]
[0004]
2-benzoylpropiononitrile was synthesized by reacting 2-benzoylpropionaldehyde with hydroxylamine hydrochloride to give 4-methyl-5-phenylisoxazole and then ring-opening with a base. They are (pharmaceutical magazines, 79, 267 (1959)). However, this method has a problem as an industrial production method because the reaction operation and post-treatment are complicated because the ring is opened after being cyclized once.
[0005]
[Problems to be solved by the invention]
The object of the present invention is to solve the above-mentioned problems and to provide an industrially suitable method for producing a β-ketonitrile derivative, which produces a β-ketonitrile derivative from a β-ketoenol derivative by a simple method.
[0006]
[Means for Solving the Problems]
The subject of this invention is general formula (1).
[0007]
[Formula 4]
[0008]
(In the formula, R 1 and R 2 may be the same or different, and may be a methyl group, an ethyl group, a propyl group, a butyl group, a phenyl group, a naphthyl group, or an anthryl group, which may have a substituent. These groups include various isomers, and the substituent is selected from the group consisting of methoxyl group, ethoxyl group, propoxyl group, butoxyl group, fluorine atom, chlorine atom, bromine atom and iodine atom. At least one substituent, M represents an alkali metal atom, a hydrogen atom or a hydrocarbon group), and a hydroxylamine-O-sulfonic acid is reacted with a β-ketoenol derivative represented by General formula (2)
[0009]
[Chemical formula 5]
[0010]
(In the formula, R 1 and R 2 are as defined above.)
This can be solved by a process for producing a β-ketonitrile derivative represented by the following formula.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
In the reaction of the present invention, R 1 and R 2 of the β-ketoenol derivative represented by the general formula (1) may be the same or different and represent groups not involved in the reaction. Specific examples include alkyl groups or aryl groups, and specific examples include alkyl groups such as methyl, ethyl, propyl, and butyl groups; and aryl groups such as phenyl, naphthyl, and anthryl groups. . These groups include various isomers.
[0012]
Examples of the substituent include alkoxyl groups such as a methoxyl group, ethoxyl group, propoxyl group, and butoxyl group; and halogen atoms such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. In addition, the number and position of a substituent are not specifically limited.
[0013]
In the general formula (1), M represents an alkali metal atom, a hydrogen atom or a hydrocarbon group. Specifically, for example, an alkali metal atom such as a lithium atom, a sodium atom or a potassium atom; a hydrogen atom; a methyl group Hydrocarbon groups such as ethyl group, propyl group, and butyl group (these hydrocarbon groups include various isomers), and preferably an alkali metal atom.
[0014]
The β-ketoenol derivative used in the reaction of the present invention is a compound that can be easily synthesized from a ketone compound and a formate ester (for example, J. Heterocyclic. Chem., 24 , 351 (1987)).
[0015]
The hydroxylamine-O-sulfonic acid used in the reaction of the present invention may be used not only as free hydroxylamine-O-sulfonic acid (including hydrates) but also as an aqueous solution thereof.
[0016]
The amount of hydroxylamine-O-sulfonic acid used is preferably 0.5 to 20 mol, more preferably 0.8 to 10 mol, relative to 1 mol of the β-ketoenol derivative.
[0017]
The reaction of the present invention is carried out in the presence or absence of a solvent. The solvent used is not particularly limited as long as it does not participate in the reaction. For example, water; alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, t-butyl alcohol; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N, N′-dimethyl-2-imidazolidone; nitriles such as acetonitrile, propionitrile, benzonitrile, etc. are preferable, but water, Alcohols, mixed solvents of water and alcohol are used. In addition, you may use these solvents individually or in mixture of 2 or more types.
[0018]
The amount of the solvent used is appropriately adjusted depending on the homogeneity and agitation of the solution, but is preferably 0.1 to 1000 ml, more preferably 1 to 100 ml with respect to 1 g of the β-ketoenol derivative.
[0019]
The reaction of the present invention is performed by, for example, a method of mixing and stirring a β-ketoenol derivative, hydroxylamine-O-sulfonic acid and a solvent in an atmosphere of an inert gas. The reaction temperature at that time is preferably 0 to 200 ° C., more preferably 5 to 100 ° C., and the reaction pressure is not particularly limited.
[0020]
The β-ketonitrile derivative obtained by the reaction of the present invention is generally treated by recrystallization, crystallization, distillation, column chromatography, etc. after the completion of the reaction, for example, after neutralization, extraction, concentration, filtration, etc. Isolated and purified by conventional methods.
[0021]
【Example】
Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.
[0022]
Reference Example 1 (Synthesis of 2-methyl-3-oxobutyraldehyde sodium salt)
In a nitrogen atmosphere, 32.41 g (0.60 mol) of sodium methoxide, 300 ml of toluene and 48 ml of ethanol were added to a 500 ml flask equipped with a stirrer, a thermometer and a dropping funnel. Then, while maintaining the reaction liquid at 0 to 5 ° C. and stirring, a mixed liquid of 43.27 g (0.60 mol) of 2-butanone and 45.79 g (0.62 mol) of ethyl formate was slowly dropped, and at the same temperature for 2 hours, Furthermore, the temperature was raised to room temperature and the reaction was carried out for 15 hours. After completion of the reaction, the mixture was filtered, and the filtrate was dried to obtain 53.76 g of sodium salt of 2-methyl-3-oxobutyraldehyde as a colorless powder (isolation yield: 73%).
The physical properties of sodium salt of 2-methyl-3-oxobutyraldehyde were as follows.
[0023]
1 H-NMR (DMSO-d 6 , δ (ppm)); 1.39 (3H, s), 1.88 (3H, s), 9.07 (1H, s)
[0024]
Example 1 (Synthesis of 3-cyano-2-butanone)
To a 300-ml flask equipped with a stirrer, thermometer and dropping funnel, 36.63 g (0.30 mol) of sodium salt of 2-methyl-3-oxobutyraldehyde synthesized in the same manner as in Reference Example 1 and 100 ml of water were added. added. Next, an aqueous solution in which 37.32 g (0.33 mol) of hydroxylamine-O-sulfonic acid is dissolved in 60 ml of water is slowly dropped while maintaining the reaction solution at 5 to 10 ° C. and stirred, and the reaction is performed at room temperature for 6 hours. It was. After completion of the reaction, the mixture was extracted twice with 150 ml of ethyl acetate. The organic layer was taken out and analyzed by gas chromatography (internal standard method). As a result, 21.80 g (reaction yield: 75%) of 3-cyano-2-butanone was produced. Thereafter, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 19.50 g of 3-cyano-2-butanone as a colorless liquid (isolation yield: 67%).
The physical properties of 3-cyano-2-butanone were as follows.
[0025]
1 H-NMR (DMSO-d 6 , δ (ppm)); 1.50 (3H, d), 2.38 (3H, s), 3.60 (1H, q)
[0026]
Example 2 (Synthesis of 3-cyano-2-butanone)
In Example 1, the reaction was performed in the same manner as in Example 1 except that the extraction solvent was changed from ethyl acetate to 1,2-dichloroethane. When the extracted organic layer (1,2-dichloroethane layer) was analyzed by gas chromatography (internal standard method), 22.10 g (reaction yield: 76%) of 3-cyano-2-butanone was produced.
[0027]
Reference Example 2 (Synthesis of 2-methyl-3-oxobutyraldehyde)
In a 200 ml flask equipped with a stirrer, thermometer and dropping funnel, 12.2 g (0,10 mol) of sodium salt of 2-methyl-3-oxobutyraldehyde synthesized in the same manner as in Reference Example 1 and 40 ml of water Was added. Subsequently, 8.3 ml of concentrated hydrochloric acid was slowly added dropwise while maintaining the reaction solution at 10 ° C. and stirring. After completion of the reaction, 50 ml of methylene chloride was added and the organic layer was taken out and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 7.0 g of 2-methyl-3-oxobutyraldehyde as a colorless powder (isolation yield: 70%).
The physical properties of 2-methyl-3-oxobutyraldehyde were as follows.
[0028]
1 H-NMR (CDCl 3 , δ (ppm)); 1.80 (3H, d), 2.14 (3H, s), 7.70-7.80 (1H, m), 14.65 (1H, d)
[0029]
Example 3 (Synthesis of 3-cyano-2-butanone)
To a 300-ml flask equipped with a stirrer, a thermometer and a dropping funnel, 30.10 g (0.30 mol) of 2-methyl-3-oxobutyraldehyde synthesized in the same manner as in the method of Reference Example 2 and 100 ml of water were added. Next, an aqueous solution in which 37.32 g (0.33 mol) of hydroxylamine-O-sulfonic acid is dissolved in 60 ml of water is slowly dropped while maintaining the reaction solution at 5 to 10 ° C. and stirred, and the reaction is performed at room temperature for 6 hours. It was. After completion of the reaction, the mixture was extracted twice with 150 ml of ethyl acetate. The organic layer was taken out and analyzed by gas chromatography (internal standard method). As a result, 19.80 g (reaction yield: 67%) of 3-cyano-2-butanone was produced.
[0030]
Reference Example 3 (Synthesis of 2-ethyl-3-oxobutyraldehyde sodium salt)
In a nitrogen atmosphere, 32.41 g (0.60 mol) of sodium methoxide, 300 ml of toluene and 48 ml of ethanol were added to a 500 ml flask equipped with a stirrer, a thermometer and a dropping funnel. Next, while stirring while maintaining the reaction solution at 0 to 5 ° C., a mixed solution of 51.68 g (0.60 mol) of 2-pentanone and 45.79 g (0.62 mol) of ethyl formate was gently added dropwise at the same temperature for 2 hours. Furthermore, the temperature was raised to room temperature and the reaction was carried out for 15 hours. After completion of the reaction, the mixture was filtered and the filtrate was dried to obtain 21.30 g of sodium salt of 2-ethyl-3-oxobutyraldehyde as a colorless powder (isolation yield: 26%).
The physical properties of sodium salt of 2-ethyl-3-oxobutyraldehyde were as follows.
[0031]
1 H-NMR (DMSO-d 6 , δ (ppm)); 0.72 (3H, t), 1.87 (3H, s), 2.02 (2H, q), 9.00 (1H, s)
[0032]
Example 4 (Synthesis of 3-cyano-2-pentanone)
To a 300-ml flask equipped with a stirrer, thermometer and dropping funnel, 40.83 g (0.30 mol) of sodium salt of 2-ethyl-3-oxobutyraldehyde synthesized in the same manner as in Reference Example 3 and 100 ml of water were added. added. Next, an aqueous solution in which 37.32 g (0.33 mol) of hydroxylamine-O-sulfonic acid is dissolved in 60 ml of water is slowly dropped while maintaining the reaction solution at 5 to 10 ° C. and stirred, and the reaction is performed at room temperature for 6 hours. It was. After completion of the reaction, extraction was performed twice with 200 ml of ethyl acetate. The organic layer was taken out and analyzed by gas chromatography (internal standard method). As a result, 25.00 g (reaction yield: 75%) of 3-cyano-2-pentanone was produced. Thereafter, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 24.30 g of 3-cyano-2-pentanone as a colorless liquid (isolated yield: 73%).
The physical properties of 3-cyano-2-pentanone were as follows.
[0033]
1 H-NMR (DMSO-d 6 , δ (ppm)); 0.97 (3H, t), 1.95 to 2.22 (2H, m), 2.26 (3H, s), 4.02 to 4.12 (1H, m)
[0034]
【The invention's effect】
INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an industrially suitable method for producing a β-ketonitrile derivative that produces a β-ketonitrile derivative from a β-ketoenol derivative by a simple method.

Claims (2)

一般式(1)
(式中、R及びRは、同一又は異なっていても良く、置換基を有していても良いメチル基、エチル基、プロピル基、ブチル基、フェニル基、ナフチル基、又はアントリル基である。なお、これらの基は各種異性体を含み、当該置換基としては、メトキシル基、エトキシル基、プロポキシル基、ブトキシル基、フッ素原子、塩素原子、臭素原子及びヨウ素原子からなる群より選ばれる少なくとも1つの置換基である。Mは、アルカリ金属原子、水素原子又は炭化水素基を示す。)で示されるβ−ケトエノール誘導体に、ヒドロキシルアミン−O−スルホン酸を反応させることを特徴とする、一般式(2)
(式中、R及びRは、前記同義である。)で示されるβ−ケトニトリル誘導体の製法。
General formula (1)
(In the formula, R 1 and R 2 may be the same or different, and may be a methyl group, an ethyl group, a propyl group, a butyl group, a phenyl group, a naphthyl group, or an anthryl group, which may have a substituent. These groups include various isomers, and the substituent is selected from the group consisting of methoxyl group, ethoxyl group, propoxyl group, butoxyl group, fluorine atom, chlorine atom, bromine atom and iodine atom. At least one substituent, M represents an alkali metal atom, a hydrogen atom or a hydrocarbon group), and a hydroxylamine-O-sulfonic acid is reacted with a β-ketoenol derivative represented by General formula (2)
(Wherein, R 1 and R 2 have the same meanings as described above).
Mが、アルカリ金属原子である請求項1記載のβ−ケトニトリル誘導体の製法。  The process for producing a β-ketonitrile derivative according to claim 1, wherein M is an alkali metal atom.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58172357A (en) * 1982-04-02 1983-10-11 Sumitomo Chem Co Ltd Preparation of nitrile
JP2002249477A (en) * 2000-12-22 2002-09-06 Ube Ind Ltd METHOD OF PRODUCING beta-KETONITRILES
JP2002275145A (en) * 2001-03-15 2002-09-25 Ube Ind Ltd Method for manufacturing 3-oxonitrile
JP2002293766A (en) * 2001-01-25 2002-10-09 Ube Ind Ltd METHOD FOR PRODUCING beta-KETONITRILES

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58172357A (en) * 1982-04-02 1983-10-11 Sumitomo Chem Co Ltd Preparation of nitrile
JP2002249477A (en) * 2000-12-22 2002-09-06 Ube Ind Ltd METHOD OF PRODUCING beta-KETONITRILES
JP2002293766A (en) * 2001-01-25 2002-10-09 Ube Ind Ltd METHOD FOR PRODUCING beta-KETONITRILES
JP2002275145A (en) * 2001-03-15 2002-09-25 Ube Ind Ltd Method for manufacturing 3-oxonitrile

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