JP4013772B2 - 2-Hydroxyimino-3-oxopropionitrile and process for producing the same - Google Patents
2-Hydroxyimino-3-oxopropionitrile and process for producing the same Download PDFInfo
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- JP4013772B2 JP4013772B2 JP2003014627A JP2003014627A JP4013772B2 JP 4013772 B2 JP4013772 B2 JP 4013772B2 JP 2003014627 A JP2003014627 A JP 2003014627A JP 2003014627 A JP2003014627 A JP 2003014627A JP 4013772 B2 JP4013772 B2 JP 4013772B2
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- oxopropionitrile
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Description
【0001】
【発明の属する技術分野】
本発明は、医薬・農薬等の中間体として有用な、新規な2-ヒドロキシイミノ-3-オキソプロピオニトリル及びその製法に関する。
【0002】
【従来の技術】
本発明の2-ヒドロキシイミノ-3-オキソプロピオニトリルは、新規化合物であり、従来にその製法は全く知られていなかった。
【0003】
【特許文献1】
特開昭60−56981号公報
【特許文献2】
特開昭62−273979号公報
【特許文献3】
特表平7−502542号公報
【非特許文献1】
「化学大辞典」第32版、第1巻、共立出版株式会社、1989年8月、p.76
【0004】
【発明が解決しようとする課題】
本発明の課題は、即ち、新規な2-ヒドロキシイミノ-3-オキソプロピオニトリル及びその製法を提供するものである。
【0005】
【課題を解決するための手段】
本発明の課題は、式(1)
【0006】
【化4】
で示される2-ヒドロキシイミノ-3-オキソプロピオニトリルによって解決される。
【0007】
本発明の課題は、又、水の存在下、一般式(2)
【0008】
【化5】
(式中、R1は、炭素数1〜4のアルキル基を示す。)
で示される3-アルコキシアクリロニトリル及び一般式(3)
【0009】
【化6】
(式中、R2及びR3は、同一又は異なっても良い、炭素数1〜4のアルキル基を示す。)
で示される3,3-ジアルコキシプロピオニトリルからなる群から選ばれた少なくとも1種のニトリル化合物にニトロソ化剤を反応させることを特徴とする、請求項1記載の2-ヒドロキシイミノ-3-オキソプロピオニトリルの製法によっても解決される。
【0010】
【発明の実施の形態】
本発明における2-ヒドロキシイミノ-3-オキソプロピオニトリルは、前記の式(1)で示される。なお、該化合物はオキシム基を有するため、E体やZ体等、幾つかの異性体が存在するが、いかなる異性体も含まれる。
【0011】
なお、2-ヒドロキシイミノ-3-オキソプロピオニトリルは、下式(4)
【0012】
【化7】
で示される工程によって5-アミノ-1-(2-ヒドロキシエチル)-4-ニトロソピラゾールに導くことが出来(参考例1及び2参照)、導かれた5-アミノ-1-(2-ヒドロキシエチル)-4-ニトロソピラゾールは、毛髪染料や、抗腫瘍剤中間体として有用な4,5-ジアミノピラゾール誘導体の合成原料として利用出来る(例えば、特許文献1、特許文献2及び特許文献3)。
【0013】
本発明の2-ヒドロキシイミノ-3-オキソプロピオニトリルは、前記の一般式(2)で示される3-アルコキシアクリロニトリル及び一般式(3)で示される3,3-ジアルコキシプロピオニトリルからなる群から選ばれた少なくとも1種のニトリル化合物にニトロソ化剤を反応させることによって得られる。
【0014】
その一般式(2)及び(3)において、R1、R2及びR3は、同一又は異なっても良い、炭素数1〜4のアルキル基を示すが、例えば、メチル基、エチル基、プロピル基、ブチル基である。なお、これらの基は、各種異性体を含む。
【0015】
一般式(2)で示される前記3-アルコキシアクリロニトリル及び一般式(3)で示される前記3,3-ジアルコキシプロピオニトリルは市販のものを用いる事ができ、入手が容易な化合物である。
【0016】
本発明の反応において使用する水としては、反応系内に直接添加する以外に、ニトロソ化剤を発生させる際に副生する水でも良く、その使用量は、ニトリル化合物 1molに対して、好ましくは0.8〜500mol、更に好ましくは 1.0〜250molである。
【0017】
本発明の反応において使用するニトロソ化剤としては、例えば、亜硝酸(非特許文献1記載の方法等によって発生させることが出来る。)、ニトロシルフルオライド、ニトロシルクロライド、ニトロシルブロマイド、ニトロシルヨーダイド等のニトロシルハライド類、ニトロシルギ酸、ニトロシル酢酸等のニトロシルカルボン酸類、ニトロシル硫酸が挙げられるが、好ましくはニトロシルハライド、ニトロシル硫酸、更に好ましくはニトロシルクロライド、ニトロシル硫酸が使用される。なお、ニトロシルハライドは、市販品又は別途合成したガスをそのまま反応系内に供給しても良いが、例えば、▲1▼アルキルナイトライトとハロゲン化水素(又はその水溶液)、▲2▼亜硝酸アルカリ金属塩とハロゲン化水素(又はその水溶液)、又は、▲3▼窒素酸化物とハロゲン化水素(又はその水溶液)を反応させる等の方法によって、直接反応系内でニトロシルハライドを発生させても良い。
【0018】
前記ニトロソ化剤の使用量は、ニトリル化合物 1molに対して、好ましくは0.5〜10mol、更に好ましくは0.8〜5molである。
【0019】
本発明の反応は、溶媒の存在下又は非存在下で行われ、溶媒を使用する場合には、反応を阻害しないものであれば特に限定されず、例えば、塩酸、硫酸等の鉱酸類、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、sec-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、アセトニトリル、プロピオニトリル等のニトリル類、ヘキサン、ヘプタン等の脂肪族炭化水素類、塩化メチレン、クロロホルム、四塩化炭素等のハロゲン化脂肪族炭化水素類、ベンゼン、トルエン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化芳香族炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、テトラヒドロフラン、ジオキサン等のエーテル類、酢酸、プロピオン酸等のカルボン酸類、N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド等のアミド類、ジメチルスルホキシド等のスルホキシド類が挙げられるが、好ましくは鉱酸類、アルコール類、エーテル類が挙げられるが、更に好ましくは塩酸、ジイソプロピルエーテルが使用される。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。
【0020】
前記溶媒の使用量は、反応液の均一性や攪拌性により適宜調整するが、ニトリル化合物1gに対して、好ましくは 0〜100g、更に好ましくは 0〜50gである。
【0021】
本発明の反応は、例えば、水の存在下、ニトリル化合物、ニトロソ化剤及び溶媒を混合して、攪拌しながら反応させ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-70〜100℃、更に好ましくは-30〜50℃であり、反応圧力は特に制限されない。
【0022】
本発明の反応によって得られる2-ヒドロキシイミノ-3-オキソプロピオニトリルは、反応終了後、濾過、抽出、濃縮、再結晶、晶析、カラムクロマトグラフィー等の一般的な方法によって単離・精製される。
【0023】
【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。
【0024】
実施例1(2-ヒドロキシイミノ-3-オキソプロピオニトリルの合成)
攪拌装置、温度計、滴下漏斗及び冷却器を備えた内容積25mlのフラスコに、97質量%の3-メトキシアクリロニトリル2.0g(23mmol)及びジイソプロピルエーテル5mlを加え、攪拌しながら-10℃まで冷却した。次いで、反応液を5℃以下に保ちながら、濃塩酸3.5mlをゆるやかに添加した。再び反応液を-10℃まで冷却後、亜硝酸ナトリウム2.0g(36mmol)と水3mlの混合液をゆるやかに滴下し、同温度で1.5時間、更に室温で2時間反応させた。反応終了後、反応液を酢酸エチルで抽出した後に有機層を分離し、飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させた。濾過後、反応液を減圧下で濃縮し、濃縮物をシリカゲルカラムクロマトグラフィー(充填剤:Micro Sphere Gel D-150-60A、展開溶媒:トルエン/酢酸エチル=1/1(容量比))で精製して、黄色油状物として2-ヒドロキシイミノ-3-オキソプロピオニトリル2.3gを得た(単離収率:100%)。更に、トルエンで再結晶させることで、淡黄色粉末として2-ヒドロキシイミノ-3-オキソプロピオニトリル0.79gを得た。
なお、2-ヒドロキシイミノ-3-オキソプロピオニトリルは以下の物性値で示される新規な化合物である。
【0025】
融点;76〜78℃
EI-MS(m/z);98,53
CI-MS(m/z);99(MH+)
1H-NMR(CDCl3,δ(ppm));9.60(1H,s)、10.64(1H,s)
IR(KBr法、cm-1);3129、2993、2831、1709、1457、1428、1273、1076、768、 745
【0026】
実施例2(2-ヒドロキシイミノ-3-オキソプロピオニトリルの合成)
実施例1と同様な装置に、97質量%の3-メトキシアクリロニトリル1.0g(11.7mmol)及び44.8質量%亜硝酸ナトリウム水溶液3.6g(23.4mmol)を加え、攪拌しながら-8℃まで冷却した。次いで、反応液を1℃以下に保ちながら、濃塩酸4.8gをゆるやかに添加した後、-5〜-1℃で1.5時間、更に室温で1時間反応させた。反応終了後、反応液をジイソプロピルエーテルで抽出した後に有機層を分離し、飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させた。濾過後、反応液を減圧下で濃縮し、濃縮物を1H-NMRで分析(内部標準法)したところ、2-ヒドロキシイミノ-3-オキソプロピオニトリルが0.83g生成していた(反応収率:73%)。
【0027】
実施例3(2-ヒドロキシイミノ-3-オキソプロピオニトリルの合成)
実施例1と同様な装置に、94質量%の3,3-ジメトキシプロピオニトリル1.0g(8.7mmol)及び44.8質量%の亜硝酸ナトリウム水溶液2.4g(15.6mmol)を加え、攪拌しながら-5℃まで冷却した。次いで、反応液を-1℃以下に保ちながら、濃塩酸3.2gをゆるやかに添加した後、-5〜-1℃で1時間、更に室温で1.5時間反応させた。反応終了後、反応液を酢酸エチルで抽出した後に有機層を分離し、飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させた。濾過後、反応液を減圧下で濃縮し、濃縮物を1H-NMRで分析(内部標準法)したところ、2-ヒドロキシイミノ-3-オキソプロピオニトリルが0.61g生成していた(反応収率:76%)。
【0028】
実施例4(2-ヒドロキシイミノ-3-オキソプロピオニトリルの合成)
攪拌装置、温度計、滴下漏斗及び冷却器を備えた内容積100mlのフラスコに、97質量%の3-メトキシアクリロニトリル3.0g(35mmol)及び水24mlを加え、反応液を0℃まで冷却した後、40質量%ニトロシル硫酸・硫酸溶液13.0g(41mmol)をゆるやかに添加し、同温度で1時間、更に室温で18時間反応させた。反応終了後、反応液をトルエンで洗浄した後に水層を分離し、酢酸エチルで抽出した。次いで、有機層を飽和食塩水で洗浄後、無水硫酸マグネシウムで乾燥させた。濾過後、反応液を減圧下で濃縮し、濃縮物をシリカゲルカラムクロマトグラフィー(充填剤:Micro Sphere Gel D-150-60A、展開溶媒:トルエン/酢酸エチル=2/1(容量比))で精製して、黄色油状物として2-ヒドロキシイミノ-3-オキソプロピオニトリル2.9gを得た(単離収率:82%)。
【0029】
参考例1(3-(2-ヒドロキシエチル)ヒドラゾノ-2-ヒドロキシイミノプロピオニトリルの合成)
実施例1と同様な装置に、実施例1と同様な方法で合成した2-ヒドロキシイミノ-3-オキソプロピオニトリル0.98g(10mmol)及びメタノール6mlを加え、攪拌しながら5℃まで冷却した。次いで、同温度で95質量%の2-ヒドロキシエチルヒドラジン0.80g(10mmol)を添加し、室温で1時間反応させた。反応終了後、反応液を減圧下で濃縮し、濃縮物にヘキサンを加えた後に、濾過して減圧下で乾燥させ、茶褐色固体として3-(2-ヒドロキシエチル)ヒドラゾノ-2-ヒドロキシイミノプロピオニトリル1.55gを得た(単離収率:99%)。
なお、3-(2-ヒドロキシエチル)ヒドラゾノ-2-ヒドロキシイミノプロピオニトリルは以下の物性値で示される新規な化合物である。
【0030】
1H-NMR(DMSO-d6,δ(ppm));3.17〜3.62(4H,m)、4.42〜5.10(1H,brs)、7.33(0.2H,s)、7.53(0.8H,s)、8.33(0.8H,t)、8.91(0.2Hz,t)、11.20〜13.10(1H,br)
【0031】
参考例2(5-アミノ-1-(2-ヒドロキシエチル)-4-ニトロソピラゾールの合成)
攪拌装置、温度計及び還流冷却器を備えた内容積25mlのフラスコに、参考例1と同様な方法で合成した3-(2-ヒドロキシエチル)ヒドラゾノ-2-ヒドロキシイミノプロピオニトリル0.94g(6mmol)及びn-ブチルアルコール6mlを加え、110℃で3時間、更に5〜10℃で1時間反応させた。反応終了後、反応液を濾過し、濾過物を減圧下で乾燥させて、赤橙色結晶として5-アミノ-1-(2-ヒドロキシエチル)-4-ニトロソピラゾール0.61gを得た(単離収率:64%)。
なお、5-アミノ-1-(2-ヒドロキシエチル)-4-ニトロソピラゾールの物性値は以下の通りであった。
【0032】
融点;170.2〜171.8℃(dec.)
EI-MS(m/z);156,125
CI-MS(m/z);157(MH+)
1H-NMR(DMSO-d6,δ(ppm));3.60〜4.03(4H,m)、4.75〜5.03(1H,br)、7.06(0.2H,s)、7.76〜8.29(2H,br)、8.53(0.8H,s)
【0033】
【発明の効果】
本発明により、医薬・農薬等の中間体として有用な、新規な2-ヒドロキシイミノ-3-オキソプロピオニトリル及びそ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 novel 2-hydroxyimino-3-oxopropionitrile useful as an intermediate for pharmaceuticals, agricultural chemicals and the like, and a process for producing the same.
[0002]
[Prior art]
The 2-hydroxyimino-3-oxopropionitrile of the present invention is a novel compound, and its production method has not been known at all.
[0003]
[Patent Document 1]
Japanese Patent Laid-Open No. 60-56981 [Patent Document 2]
Japanese Patent Laid-Open No. 62-273379 [Patent Document 3]
JP 7-502542 A [Non-patent Document 1]
“Chemical Dictionary”, 32nd edition, Volume 1, Kyoritsu Publishing Co., Ltd. 76
[0004]
[Problems to be solved by the invention]
An object of the present invention is to provide a novel 2-hydroxyimino-3-oxopropionitrile and a process for producing the same.
[0005]
[Means for Solving the Problems]
The subject of this invention is Formula (1).
[0006]
[Formula 4]
It is solved by 2-hydroxyimino-3-oxopropionitrile represented by
[0007]
The subject of the present invention is also the general formula (2) in the presence of water.
[0008]
[Chemical formula 5]
(In the formula, R 1 represents an alkyl group having 1 to 4 carbon atoms.)
3-alkoxyacrylonitrile represented by the general formula (3)
[0009]
[Chemical 6]
(Wherein R 2 and R 3 represent the same or different alkyl group having 1 to 4 carbon atoms)
The 2-hydroxyimino-3- of claim 1, wherein the nitrosating agent is reacted with at least one nitrile compound selected from the group consisting of 3,3-dialkoxypropionitrile represented by formula (1). It can also be solved by the production method of oxopropionitrile.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
The 2-hydroxyimino-3-oxopropionitrile in the present invention is represented by the above formula (1). In addition, since this compound has an oxime group, there are several isomers such as E-form and Z-form, but any isomer is included.
[0011]
In addition, 2-hydroxyimino-3-oxopropionitrile has the following formula (4)
[0012]
[Chemical 7]
Can be led to 5-amino-1- (2-hydroxyethyl) -4-nitrosopyrazole (see Reference Examples 1 and 2), and the derived 5-amino-1- (2-hydroxyethyl) can be obtained. ) -4-nitrosopyrazole can be used as a raw material for synthesizing 4,5-diaminopyrazole derivatives useful as hair dyes or antitumor agent intermediates (for example, Patent Document 1, Patent Document 2 and Patent Document 3).
[0013]
The 2-hydroxyimino-3-oxopropionitrile of the present invention comprises 3-alkoxyacrylonitrile represented by the general formula (2) and 3,3-dialkoxypropionitrile represented by the general formula (3). It is obtained by reacting a nitrosating agent with at least one nitrile compound selected from the group.
[0014]
In the general formulas (2) and (3), R 1 , R 2 and R 3 may be the same or different and each represents an alkyl group having 1 to 4 carbon atoms. For example, a methyl group, an ethyl group, and propyl Group, butyl group. These groups include various isomers.
[0015]
As the 3-alkoxyacrylonitrile represented by the general formula (2) and the 3,3-dialkoxypropionitrile represented by the general formula (3), commercially available ones can be used, and these are readily available compounds.
[0016]
The water used in the reaction of the present invention may be water by-produced when generating a nitrosating agent, in addition to being directly added to the reaction system, and the amount used is preferably 1 mol of the nitrile compound. 0.8 to 500 mol, more preferably 1.0 to 250 mol.
[0017]
Examples of the nitrosating agent used in the reaction of the present invention include nitrous acid (can be generated by the method described in Non-Patent Document 1, etc.), nitrosyl fluoride, nitrosyl chloride, nitrosyl bromide, nitrosyl iodide and the like. Nitrosyl halides, nitrosylcarboxylic acids such as nitrosylformic acid and nitrosylacetic acid, and nitrosylsulfuric acid can be mentioned, and nitrosylhalide and nitrosylsulfuric acid are preferable, and nitrosylchloride and nitrosylsulfuric acid are more preferable. The nitrosyl halide may be a commercially available product or a separately synthesized gas supplied as it is into the reaction system. For example, (1) alkyl nitrite and hydrogen halide (or an aqueous solution thereof), (2) alkali nitrite Nitrosyl halide may be generated directly in the reaction system by a method such as reacting a metal salt with hydrogen halide (or an aqueous solution thereof) or (3) reacting nitrogen oxide with hydrogen halide (or an aqueous solution thereof). .
[0018]
The amount of the nitrosating agent to be used is preferably 0.5 to 10 mol, more preferably 0.8 to 5 mol, per 1 mol of the nitrile compound.
[0019]
The reaction of the present invention is carried out in the presence or absence of a solvent, and when a solvent is used, it is not particularly limited as long as it does not inhibit the reaction. For example, mineral acids such as hydrochloric acid and sulfuric acid, methanol , Ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, sec-butyl alcohol, t-butyl alcohol and other alcohols, acetonitrile, propionitrile and other nitriles, hexane, heptane and other aliphatics Hydrocarbons, halogenated aliphatic hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, aromatic hydrocarbons such as benzene and toluene, halogenated aromatic hydrocarbons such as chlorobenzene, diethyl ether, diisopropyl ether, Ethers such as tetrahydrofuran and dioxane, acetic acid, propionic acid, etc. Carboxylic acids, amides such as N, N-dimethylformamide and N, N-dimethylacetamide, and sulfoxides such as dimethyl sulfoxide, preferably mineral acids, alcohols and ethers, more preferably Hydrochloric acid and diisopropyl ether are used. In addition, you may use these solvents individually or in mixture of 2 or more types.
[0020]
The amount of the solvent used is appropriately adjusted depending on the uniformity and stirrability of the reaction solution, but is preferably 0 to 100 g, more preferably 0 to 50 g based on 1 g of the nitrile compound.
[0021]
The reaction of the present invention is carried out, for example, by a method of mixing a nitrile compound, a nitrosating agent and a solvent in the presence of water and reacting them with stirring. The reaction temperature at that time is preferably −70 to 100 ° C., more preferably −30 to 50 ° C., and the reaction pressure is not particularly limited.
[0022]
2-Hydroxyimino-3-oxopropionitrile obtained by the reaction of the present invention is isolated and purified by a general method such as filtration, extraction, concentration, recrystallization, crystallization, column chromatography after completion of the reaction. Is done.
[0023]
【Example】
Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.
[0024]
Example 1 (Synthesis of 2-hydroxyimino-3-oxopropionitrile)
To a flask with an internal volume of 25 ml equipped with a stirrer, thermometer, dropping funnel and cooler, 2.0 g (23 mmol) of 97% by mass of 3-methoxyacrylonitrile and 5 ml of diisopropyl ether were added and cooled to −10 ° C. with stirring. . Subsequently, 3.5 ml of concentrated hydrochloric acid was slowly added while keeping the reaction solution at 5 ° C. or lower. The reaction solution was again cooled to −10 ° C., and a mixed solution of 2.0 g (36 mmol) of sodium nitrite and 3 ml of water was slowly added dropwise and reacted at the same temperature for 1.5 hours and further at room temperature for 2 hours. After completion of the reaction, the reaction solution was extracted with ethyl acetate, the organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the reaction solution is concentrated under reduced pressure, and the concentrate is purified by silica gel column chromatography (filler: Micro Sphere Gel D-150-60A, developing solvent: toluene / ethyl acetate = 1/1 (volume ratio)). As a result, 2.3 g of 2-hydroxyimino-3-oxopropionitrile was obtained as a yellow oil (isolation yield: 100%). Furthermore, recrystallization from toluene gave 0.79 g of 2-hydroxyimino-3-oxopropionitrile as a pale yellow powder.
2-Hydroxyimino-3-oxopropionitrile is a novel compound represented by the following physical properties.
[0025]
Melting point: 76-78 ° C
EI-MS (m / z); 98, 53
CI-MS (m / z); 99 (MH + )
1 H-NMR (CDCl 3 , δ (ppm)); 9.60 (1H, s), 10.64 (1H, s)
IR (KBr method, cm −1 ); 3129, 2993, 2831, 1709, 1457, 1428, 1273, 1076, 768, 745
[0026]
Example 2 (Synthesis of 2-hydroxyimino-3-oxopropionitrile)
To the same apparatus as in Example 1, 1.0 g (11.7 mmol) of 97% by mass of 3-methoxyacrylonitrile and 3.6 g (23.4 mmol) of 44.8% by mass sodium nitrite aqueous solution were added and cooled to −8 ° C. with stirring. Next, 4.8 g of concentrated hydrochloric acid was slowly added while keeping the reaction solution at 1 ° C. or lower, and then reacted at −5 to −1 ° C. for 1.5 hours and further at room temperature for 1 hour. After completion of the reaction, the reaction solution was extracted with diisopropyl ether, the organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the reaction solution was concentrated under reduced pressure, and the concentrate was analyzed by 1 H-NMR (internal standard method). As a result, 0.83 g of 2-hydroxyimino-3-oxopropionitrile was formed (reaction yield). Rate: 73%).
[0027]
Example 3 (Synthesis of 2-hydroxyimino-3-oxopropionitrile)
To the same apparatus as Example 1, 1.0 g (8.7 mmol) of 94% by mass of 3,3-dimethoxypropionitrile and 2.4 g (15.6 mmol) of 44.8% by mass of sodium nitrite aqueous solution were added and stirred. Cooled to ° C. Next, while maintaining the reaction solution at -1 ° C or lower, 3.2 g of concentrated hydrochloric acid was slowly added, followed by reaction at -5 to -1 ° C for 1 hour and further at room temperature for 1.5 hours. After completion of the reaction, the reaction solution was extracted with ethyl acetate, the organic layer was separated, washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the reaction solution was concentrated under reduced pressure, and the concentrate was analyzed by 1 H-NMR (internal standard method). As a result, 0.61 g of 2-hydroxyimino-3-oxopropionitrile was formed (reaction yield). (Rate: 76%).
[0028]
Example 4 (Synthesis of 2-hydroxyimino-3-oxopropionitrile)
To a 100 ml flask equipped with a stirrer, a thermometer, a dropping funnel and a condenser, 3.0 g (35 mmol) of 97% by mass of 3-methoxyacrylonitrile and 24 ml of water were added, and the reaction solution was cooled to 0 ° C. 13.0 g (41 mmol) of a 40 mass% nitrosylsulfuric acid / sulfuric acid solution was slowly added, and the mixture was reacted at the same temperature for 1 hour and further at room temperature for 18 hours. After completion of the reaction, the reaction solution was washed with toluene, and then the aqueous layer was separated and extracted with ethyl acetate. Next, the organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. After filtration, the reaction solution is concentrated under reduced pressure, and the concentrate is purified by silica gel column chromatography (filler: Micro Sphere Gel D-150-60A, developing solvent: toluene / ethyl acetate = 2/1 (volume ratio)). As a result, 2.9 g of 2-hydroxyimino-3-oxopropionitrile was obtained as a yellow oil (isolation yield: 82%).
[0029]
Reference Example 1 (Synthesis of 3- (2-hydroxyethyl) hydrazono-2-hydroxyiminopropionitrile)
To the same apparatus as in Example 1, 0.98 g (10 mmol) of 2-hydroxyimino-3-oxopropionitrile synthesized in the same manner as in Example 1 and 6 ml of methanol were added and cooled to 5 ° C. with stirring. Subsequently, 0.80 g (10 mmol) of 95% by mass of 2-hydroxyethylhydrazine was added at the same temperature and reacted at room temperature for 1 hour. After completion of the reaction, the reaction solution was concentrated under reduced pressure, hexane was added to the concentrate, filtered and dried under reduced pressure, and 3- (2-hydroxyethyl) hydrazono-2-hydroxyiminopropio was obtained as a brown solid. 1.55 g of nitrile was obtained (isolation yield: 99%).
Note that 3- (2-hydroxyethyl) hydrazono-2-hydroxyiminopropionitrile is a novel compound represented by the following physical property values.
[0030]
1 H-NMR (DMSO-d 6 , δ (ppm)); 3.17 to 3.62 (4H, m), 4.42 to 5.10 (1H, brs), 7.33 (0.2H, s), 7.53 (0.8H, s), 8.33 (0.8H, t), 8.91 (0.2Hz, t), 11.20-13.10 (1H, br)
[0031]
Reference Example 2 (Synthesis of 5-amino-1- (2-hydroxyethyl) -4-nitrosopyrazole)
In a flask with an internal volume of 25 ml equipped with a stirrer, a thermometer and a reflux condenser, 0.94 g (6 mmol) of 3- (2-hydroxyethyl) hydrazono-2-hydroxyiminopropionitrile synthesized in the same manner as in Reference Example 1 was prepared. ) And 6 ml of n-butyl alcohol were added and reacted at 110 ° C. for 3 hours and further at 5-10 ° C. for 1 hour. After completion of the reaction, the reaction solution was filtered, and the filtrate was dried under reduced pressure to obtain 0.61 g of 5-amino-1- (2-hydroxyethyl) -4-nitrosopyrazole as reddish orange crystals (isolated product). (Rate: 64%).
The physical properties of 5-amino-1- (2-hydroxyethyl) -4-nitrosopyrazole were as follows.
[0032]
Melting point: 170.2-171.8 ° C (dec.)
EI-MS (m / z); 156, 125
CI-MS (m / z); 157 (MH + )
1 H-NMR (DMSO-d 6 , δ (ppm)); 3.60 to 4.03 (4H, m), 4.75 to 5.03 (1H, br), 7.06 (0.2H, s), 7.76 to 8.29 (2H, br) 8.53 (0.8H, s)
[0033]
【The invention's effect】
According to the present invention, it is possible to provide a novel 2-hydroxyimino-3-oxopropionitrile useful as an intermediate for pharmaceuticals, agricultural chemicals and the like, and a method for producing the 2-hydroxyimino-3-oxopropionitrile.
Claims (2)
で示される3-アルコキシアクリロニトリル及び一般式(3)
で示される3,3-ジアルコキシプロピオニトリルからなる群から選ばれた少なくとも1種のニトリル化合物にニトロソ化剤を反応させることを特徴とする、請求項1記載の2-ヒドロキシイミノ-3-オキソプロピオニトリルの製法。General formula (2) in the presence of water
3-alkoxyacrylonitrile represented by the general formula (3)
The 2-hydroxyimino-3- of claim 1, wherein the nitrosating agent is reacted with at least one nitrile compound selected from the group consisting of 3,3-dialkoxypropionitrile represented by formula (1). Production method of oxopropionitrile.
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