JP3855686B2 - 3,3-dialkoxy-2-hydroxyimino derivative and process for producing the same - Google Patents

3,3-dialkoxy-2-hydroxyimino derivative and process for producing the same Download PDF

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JP3855686B2
JP3855686B2 JP2001176897A JP2001176897A JP3855686B2 JP 3855686 B2 JP3855686 B2 JP 3855686B2 JP 2001176897 A JP2001176897 A JP 2001176897A JP 2001176897 A JP2001176897 A JP 2001176897A JP 3855686 B2 JP3855686 B2 JP 3855686B2
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alcohol
dialkoxy
reaction
hydroxyimino
formula
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JP2002371049A (en
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泰久 福田
庄司 敷田
正 村上
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Ube Corp
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Ube Industries Ltd
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Priority to JP2001176897A priority Critical patent/JP3855686B2/en
Priority to EP02736058A priority patent/EP1408025B1/en
Priority to US10/480,576 priority patent/US7227032B2/en
Priority to PCT/JP2002/005827 priority patent/WO2002100821A1/en
Priority to DE60223683T priority patent/DE60223683T2/en
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Description

【0001】
【発明の属する技術分野】
本発明は、医薬・農薬等の中間原料として有用な、新規な3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体に関する。
【0002】
【従来の技術】
本発明の3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体は、新規な化合物であり、従来までにその製造法は全く知られていなかった。
【0003】
【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3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体及びその製造法を提供するものである。
【0004】
【課題を解決するための手段】
本発明の課題は、一般式(1)
【0005】
【化3】

Figure 0003855686
【0006】
(式中、R1及びR2は、同一又は異なっていても良く、炭素数1〜8のアルキル基を示し、R3は、シアノ基を示す。)
で示される3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体によって解決される。
【0007】
本発明の課題は、又、アルコールの存在下、一般式(2)
【0008】
【化4】
Figure 0003855686
【0009】
(式中、R3は、前記と同義であり、R4は、炭素数1〜4のアルキル基を示す。)
で示されるエノールエーテル化合物にニトロシルハライドを反応させることを特徴とする、3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体の製造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、3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体は、前記の一般式(1)で示される。
【0011】
その一般式(1)において、R1及びR2は、同一又は異なっていても良く、炭素数1〜8のアルキル基を示し、例えば、メチル基、エチル基、プロピル基、ブチル基、ペンチル基、ヘキシル基、ヘプチル基、オクチル基、好ましくはメチル基、ブチル基である。これらの基は、各種異性体も含む。又、R3は、シアノ基を示す。なお、本発明の3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体は、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。
【0012】
なお、前記3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体、特に、3,3-ジアルコキシ-2-ヒドロキシイミノプロピオニトリルは、塩酸の存在下、2-ヒドロキシエチルヒドラジンと反応させることによって、式(3)
【0013】
【化5】
Figure 0003855686
【0014】
で示される5-アミノ-1-ヒドロキシエチル-4-ニトロソピラゾール塩酸塩に導くことが出来(後の参考例1に記載)、導かれた5-アミノ-1-ヒドロキシエチル-4-ニトロソピラゾール塩酸塩は、抗腫瘍剤の有効成分であるピラゾロピラジン誘導体の合成原料として利用出来る(例えば、特開昭60-56981号公報、特開昭62-273979号公報)。
【0015】
本発明の3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体は、アルコールの存在下、前記の一般式(2)で示されるエノールエーテル化合物にニトロシルハライドを反応させることによって得られる。
【0016】
その一般式(2)において、R3は、前記と同義であり、R4は、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。これらの基は、各種異性体も含む。
【0017】
本発明の反応において使用されるアルコールとしては、炭素数1〜8のアルキル基(各種異性体を含む)を有するアルコールであり、例えば、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、t-ブチルアルコール、ペンチルアルコール、ヘキシルアルコール、ヘプチルアルコール、オクチルアルコールが挙げられるが、好ましくはメタノール、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、t-ブチルアルコール、更に好ましくはメタノールが使用される。
【0018】
前記アルコールの使用量は、エノールエーテル化合物1molに対して、好ましくは0.5〜100mol、更に好ましくは0.8〜50molである。
【0019】
なお、アルコールは反応系内に直接添加しても良いが、後述に記載のように、ニトロシルハライドを系内で発生させる際に同時に生成するアルコールを利用しても良い。
【0020】
本発明の反応において使用されるニトロシルハライドとしては、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が挙げられるが、好ましくはニトロシルクロライドが使用される。
【0021】
前記ニトロシルハライドは、市販品をそのまま使用しても良いが、例えば、▲1▼アルキルナイトライトとハロゲン化水素との反応させる方法(ニトロシルハライドとアルキルアルコールが生成)、又は、▲2▼亜硝酸アルカリ金属塩とハロゲン化水素を反応させる方法(ニトロシルハライドとアルカリ金属ハロゲン化塩が生成)等の方法によって、ニトロシルハライドを発生させて使用しても良い。
【0022】
なお、ニトロシルハライドの反応系内への供給方法としては、市販品又は前記▲1▼や▲2▼等の方法により別途発生させたニトロシルハライドを反応系内に供給しても良いが、直接反応系内で前記▲1▼や▲2▼等の反応を行いニトロシルハライドを発生してそれを使用しても構わない(その際には、反応系内にアルキルアルコール(▲1▼の場合)又はアルカリ金属ハロゲン化塩(▲2▼の場合)が混入する。)。また、ニトロシルハライドは、反応に不活性なガスで希釈して供給しても良い。
【0023】
前記ニトロシルハライドの使用量は、エノールエーテル化合物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。
【0024】
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ならば特に限定されず、例えば、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、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;ジエチルエーテル、テトラヒドロフラン、ジオキサン等のエーテル類;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;酢酸、プロピオン酸等のカルボン酸類が挙げられるが、好ましくはアルコール類が使用される。
【0025】
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節するが、エノールエーテル化合物1gに対して、好ましくは0〜100g、更に好ましくは0〜50gである。
【0026】
本発明の反応は、例えば、エノールエーテル化合物及びアルコールを混合し、ニトロシルハライドを供給して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-70〜50℃、更に好ましくは-30〜40℃であり、反応圧力は特に制限されない。
【0027】
本発明の反応によって得られる3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体は、反応終了後、晶析、再結晶、蒸留、カラムクロマトグラフィー等による一般的な方法によって単離・精製される。
【0028】
【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。
【0029】
実施例1(3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリルの合成)
攪拌装置、温度計、冷却器及びガス導入管を備えた内容積300mlのフラスコに、3-メトキシアクリロニトリル41.55g(0.5mol)及びメタノール125mlを加え、攪拌しながら-30℃まで冷却した。次いで、反応液を-10〜0℃に維持し、別容器にて41質量%亜硝酸ナトリウム水溶液170.5g(1.0mol)と濃塩酸320ml(3.5mol)を反応させて発生させたニトロシルクロライド(前記▲2▼の方法)を反応液に供給しながら、-10〜0℃で3時間、室温で2時間反応させた。反応終了後、反応液を減圧下で濃縮し、濃縮物をn-ヘキサン、トルエンの順で洗浄し、減圧下40℃で乾燥させ、淡黄色固体として2-ヒドロキシイミノ-3,3-ジメトキシプロピオニトリル61.6g(単離収率:80%)を得た。
なお、3,3-ジメトキシ-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】
融点;113〜116℃
EI-MS(m/z);113、75、54
CI-MS(m/z);145(MH+)
1H-NMR(CDCl3,δ(ppm));3.46(6H,s)、4.97(1H,s)、8.82(1H,brs)IR(KBr法、cm-1);3242、3215、2234、1450、1038、933、798
元素分析;炭素41.40%、水素5.53%、窒素19.44%
(理論値(C5H8N2O3);炭素41.67%、水素5.59%、窒素19.44%)
【0031】
実施例2(3,3-ジ-n-ブトキシ-2-ヒドロキシイミノプロピオニトリル、3-n-ブトキシ-2-ヒドロキシイミノ-3-メトキシプロピオニトリル及び3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリルの合成)
3-メトキシアクリロニトリル5.0g(60mmol)、n-ブチルナイトライト6.5g(60mmol)及びジエチルエーテル30mlを室温で混合した。次いで、攪拌装置を備えた内容積25mlのフラスコに、前記溶液5mlを加えた。攪拌しながら、25質量%塩化水素メタノール溶液1ml(6mol)をゆるやかに滴下して、ニトロシルハライドとn-ブチルアルコールを反応系内で発生させ(前記▲1▼の方法)、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、濃縮物に水を加えた後にトルエンで抽出した。有機層を取り出し、飽和炭酸水素ナトリウム水溶液で洗浄し、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、濃縮物をシリカゲルカラムクロマトグラフィー(充填剤;ワコーゲルC-200(和光純薬社製)、展開溶媒;トルエン/酢酸エチル=10/1(容量比))で精製して、無色油状物として3,3-ジ-n-ブトキシ-2-ヒドロキシイミノプロピオニトリル0.06g(単離収率:4%)、無色油状物として3-n-ブトキシ-2-ヒドロキシイミノ-3-メトキシプロピオニトリル0.21g(単離収率:19%)及び白色固体として3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリル0.14g(単離収率:16%)を得た。
なお、3,3-ジ-n-ブトキシ-2-ヒドロキシイミノプロピオニトリル及び3-n-ブトキシ-2-ヒドロキシイミノ-3-メトキシ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。
【0032】
3,3-ジ-n-ブトキシ-2-ヒドロキシイミノプロピオニトリルの物性値
CI-MS(m/z);229(MH+)、200、155、126
1H-NMR(CDCl3,δ(ppm));0.93(6H,t)、1.34〜1.66(8H,m)、3.50〜3.71(4H,m)、6.47(1H,s)、8.55(1H,s)
【0033】
3-n-ブトキシ-2-ヒドロキシイミノ-3-メトキシプロピオニトリルの物性値
CI-MS(m/z);187(MH+)、155、113、84
1H-NMR(CDCl3,δ(ppm));0.94(3H,t)、1.35〜1.68(4H,m)、3.46(3H,s)、3.51〜3.72(2H,m)、5.02(1H,s)、9.14(1H,s)
【0034】
実施例3(3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリルの合成)
攪拌装置及び滴下漏斗を備えた内容積100mlのフラスコに、3-メトキシアクリロニトリル3.0g(36mmol)、25質量%塩化水素メタノール溶液9.0g(63mmol)及びメタノール15mlを加えた。攪拌しながら、n-ブチルナイトライト4.7g(43mmol)をゆるやかに滴下して、ニトロシルハライドとn-ブチルアルコールを系内で発生させ(前記▲1▼の方法)、室温で26時間反応させた。反応終了後、飽和炭酸水素ナトリウムを加えて中和し、減圧下で反応液からメタノールを留去した。水層を酢酸エチルで抽出し、有機層を取り出して飽和食塩水で洗浄して、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、濃縮物をトルエンで再結晶して、白色固体として3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリル2.6g(単離収率:50%)を得た。
【0035】
参考例1(5-アミノ-1-ヒドロキシ-4-ニトロソピラゾール塩酸塩の合成)
攪拌装置、温度計及び還流冷却器を備えた内容積100mlのフラスコに、実施例1と同様な方法で合成した3,3-ジメトキシ-2-ヒドロキシイミノプロピオニトリル7.93g(55mmol)、2-ヒドロキシエチルヒドラジン4.01g(50mmol)、エタノール50ml及び濃塩酸7.60g(75mmol)を加え、還流下(76〜79℃)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、濃縮物にトルエン20ml及びイソプロピルアルコール20mlを加え、1時間攪拌させた。次いで、この溶液を濾過し、濾過物を減圧下40℃で乾燥させ、黄色固体として5-アミノ-1-ヒドロキシ-4-ニトロソピラゾール塩酸塩6.85g(単離収率:72%)を得た。
なお、5-アミノ-1-ヒドロキシ-4-ニトロソピラゾール塩酸塩の物性値は以下の通りであった。
【0036】
融点;164.8〜166.6℃(dec.)
1H-NMR(DMSO-d6,δ(ppm));3.65〜4.13(4H,m)、6.80〜10.40(5H,m)IR(KBr法、cm-1);3290、3063、2635、1670、1623、1208、1099、1063、1002、716
【0037】
【発明の効果】
本発明により、新規な3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体及びその製造法を提供することが出来る。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel 3,3-dialkoxy-2-hydroxyimino derivative useful as an intermediate raw material for pharmaceuticals and agricultural chemicals.
[0002]
[Prior art]
The 3,3-dialkoxy-2-hydroxyimino derivative of the present invention is a novel compound, and no production method has been known so far.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide a novel 3,3-dialkoxy-2-hydroxyimino derivative and a method for producing the same.
[0004]
[Means for Solving the Problems]
The subject of this invention is general formula (1).
[0005]
[Chemical 3]
Figure 0003855686
[0006]
(In formula, R < 1 > and R < 2 > may be same or different, shows a C1-C8 alkyl group, and R < 3 > shows a cyano group.)
It is solved by a 3,3-dialkoxy-2-hydroxyimino derivative represented by
[0007]
The subject of the present invention is also the general formula (2) in the presence of alcohol.
[0008]
[Formula 4]
Figure 0003855686
[0009]
(In the formula, R 3 has the same meaning as described above, and R 4 represents an alkyl group having 1 to 4 carbon atoms.)
It can also be solved by a method for producing a 3,3-dialkoxy-2-hydroxyimino derivative characterized in that a nitrosyl halide is reacted with an enol ether compound represented by the formula:
[0010]
DETAILED DESCRIPTION OF THE INVENTION
The 3,3-dialkoxy-2-hydroxyimino derivative in the present invention is represented by the general formula (1).
[0011]
In the general formula (1), R 1 and R 2 may be the same or different and each represents an alkyl group having 1 to 8 carbon atoms, such as a methyl group, an ethyl group, a propyl group, a butyl group, or a pentyl group. Hexyl group, heptyl group, octyl group, preferably methyl group and butyl group. These groups include various isomers. R 3 represents a cyano group. In addition, since the 3,3-dialkoxy-2-hydroxyimino derivative of the present invention has an oxime group, there are several isomers such as E-form and Z-form, and any isomer is included.
[0012]
The 3,3-dialkoxy-2-hydroxyimino derivative, particularly 3,3-dialkoxy-2-hydroxyiminopropionitrile is reacted with 2-hydroxyethylhydrazine in the presence of hydrochloric acid, Formula (3)
[0013]
[Chemical formula 5]
Figure 0003855686
[0014]
To 5-amino-1-hydroxyethyl-4-nitrosopyrazole hydrochloride (described in Reference Example 1 later), and the derived 5-amino-1-hydroxyethyl-4-nitrosopyrazole hydrochloride The salt can be used as a raw material for synthesizing a pyrazolopyrazine derivative that is an active ingredient of an antitumor agent (for example, JP-A-60-56981 and JP-A-62-273979).
[0015]
The 3,3-dialkoxy-2-hydroxyimino derivative of the present invention can be obtained by reacting a nitrosyl halide with the enol ether compound represented by the general formula (2) in the presence of an alcohol.
[0016]
In the general formula (2), R 3 has the same meaning as described above, and R 4 represents an alkyl group having 1 to 4 carbon atoms, and is, for example, a methyl group, an ethyl group, a propyl group, or a butyl group. These groups include various isomers.
[0017]
The alcohol used in the reaction of the present invention is an alcohol having an alkyl group having 1 to 8 carbon atoms (including various isomers) such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl. Alcohol, t-butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol are mentioned, preferably methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, t-butyl alcohol, more preferably Methanol is used.
[0018]
The amount of the alcohol used is preferably 0.5 to 100 mol, more preferably 0.8 to 50 mol, with respect to 1 mol of the enol ether compound.
[0019]
The alcohol may be added directly to the reaction system, but as described later, an alcohol that is simultaneously generated when nitrosyl halide is generated in the system may be used.
[0020]
Examples of the nitrosyl halide used in the reaction of the present invention include nitrosyl fluoride, nitrosyl chloride, nitrosyl bromide, and nitrosyl iodide, and nitrosyl chloride is preferably used.
[0021]
As the nitrosyl halide, a commercially available product may be used as it is. For example, (1) a method of reacting alkyl nitrite and hydrogen halide (nitrosyl halide and alkyl alcohol are produced), or (2) nitrous acid. Nitrosyl halides may be generated and used by a method such as a method of reacting an alkali metal salt with a hydrogen halide (formation of a nitrosyl halide and an alkali metal halide salt).
[0022]
As a method for supplying nitrosyl halide into the reaction system, a commercially available product or nitrosyl halide separately generated by the method (1) or (2) may be supplied into the reaction system, but direct reaction Nitrosyl halide may be generated by using the reaction (1) or (2) in the system and used (in this case, alkyl alcohol (in the case of (1)) or Alkali metal halide salt (in the case of (2)) is mixed in.) The nitrosyl halide may be supplied after being diluted with a gas inert to the reaction.
[0023]
The amount of the nitrosyl halide to be used is preferably 0.5 to 10 mol, more preferably 0.8 to 5 mol, with respect to 1 mol of the enol ether compound.
[0024]
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, methanol, ethanol, n-propyl alcohol, isopropyl Alcohols such as alcohol, n-butyl alcohol and t-butyl alcohol; Nitriles such as acetonitrile and propionitrile; Ethers such as diethyl ether, tetrahydrofuran and dioxane; Halogenated fats such as methylene chloride, chloroform and carbon tetrachloride Aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; and carboxylic acids such as acetic acid and propionic acid, but alcohols are preferably used.
[0025]
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 enol ether compound.
[0026]
The reaction of the present invention is performed, for example, by a method in which an enol ether compound and an alcohol are mixed and a nitrosyl halide is supplied and reacted. The reaction temperature at that time is preferably −70 to 50 ° C., more preferably −30 to 40 ° C., and the reaction pressure is not particularly limited.
[0027]
The 3,3-dialkoxy-2-hydroxyimino derivative obtained by the reaction of the present invention is isolated and purified by a general method such as crystallization, recrystallization, distillation, column chromatography and the like after completion of the reaction.
[0028]
【Example】
Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.
[0029]
Example 1 (Synthesis of 3,3-dimethoxy-2-hydroxyiminopropionitrile)
To a flask having an internal volume of 300 ml equipped with a stirrer, a thermometer, a cooler and a gas introduction tube, 41.55 g (0.5 mol) of 3-methoxyacrylonitrile and 125 ml of methanol were added and cooled to −30 ° C. while stirring. Subsequently, the reaction solution was maintained at −10 to 0 ° C., and nitrosilkyl chloride generated by reacting 170.5 g (1.0 mol) of a 41 mass% sodium nitrite aqueous solution with 320 ml (3.5 mol) of concentrated hydrochloric acid in a separate container (described above) While supplying the method (2) to the reaction solution, the reaction was carried out at −10 to 0 ° C. for 3 hours and at room temperature for 2 hours. After completion of the reaction, the reaction solution is concentrated under reduced pressure, and the concentrate is washed with n-hexane and toluene in that order, and dried at 40 ° C. under reduced pressure to give 2-hydroxyimino-3,3-dimethoxypropyl as a pale yellow solid. 61.6 g of pionitrile (isolation yield: 80%) was obtained.
3,3-dimethoxy-2-hydroxyiminopropionitrile is a novel compound represented by the following physical property values.
[0030]
Melting point: 113-116 ° C
EI-MS (m / z); 113, 75, 54
CI-MS (m / z); 145 (MH + )
1 H-NMR (CDCl 3 , δ (ppm)); 3.46 (6H, s), 4.97 (1H, s), 8.82 (1H, brs) IR (KBr method, cm −1 ); 3242, 3215, 2234, 1450, 1038, 933, 798
Elemental analysis: carbon 41.40%, hydrogen 5.53%, nitrogen 19.44%
(Theoretical value (C 5 H 8 N 2 O 3 ); carbon 41.67%, hydrogen 5.59%, nitrogen 19.44%)
[0031]
Example 2 (3,3-di-n-butoxy-2-hydroxyiminopropionitrile, 3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile and 3,3-dimethoxy-2-hydroxyimino Synthesis of propionitrile)
3-methoxyacrylonitrile 5.0 g (60 mmol), n-butyl nitrite 6.5 g (60 mmol) and diethyl ether 30 ml were mixed at room temperature. Next, 5 ml of the solution was added to a 25 ml flask equipped with a stirrer. While stirring, 1 ml (6 mol) of a 25% by mass hydrogen chloride methanol solution is slowly added dropwise to generate nitrosyl halide and n-butyl alcohol in the reaction system (method (1) above), and the reaction is performed at room temperature for 1 hour. I let you. After completion of the reaction, the reaction solution was concentrated under reduced pressure, and water was added to the concentrate, followed by extraction with toluene. The organic layer was taken out, washed with a saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was subjected to silica gel column chromatography (filler: Wako Gel C-200 (manufactured by Wako Pure Chemical Industries, Ltd.), developing solvent: toluene / ethyl acetate = 10/1 (volume ratio)) To give 0.06 g of 3,3-di-n-butoxy-2-hydroxyiminopropionitrile as a colorless oil (isolation yield: 4%), 3-n-butoxy-2- Obtained 0.21 g of hydroxyimino-3-methoxypropionitrile (isolation yield: 19%) and 0.14 g of 3,3-dimethoxy-2-hydroxyiminopropionitrile (isolation yield: 16%) as a white solid It was.
3,3-di-n-butoxy-2-hydroxyiminopropionitrile and 3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile are novel compounds represented by the following physical properties. .
[0032]
Physical properties of 3,3-di-n-butoxy-2-hydroxyiminopropionitrile
CI-MS (m / z); 229 (MH + ), 200, 155, 126
1 H-NMR (CDCl 3 , δ (ppm)); 0.93 (6H, t), 1.34 to 1.66 (8H, m), 3.50 to 3.71 (4H, m), 6.47 (1H, s), 8.55 (1H, s)
[0033]
Physical properties of 3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile
CI-MS (m / z); 187 (MH + ), 155, 113, 84
1 H-NMR (CDCl 3 , δ (ppm)); 0.94 (3H, t), 1.35 to 1.68 (4H, m), 3.46 (3H, s), 3.51 to 3.72 (2H, m), 5.02 (1H, s), 9.14 (1H, s)
[0034]
Example 3 (Synthesis of 3,3-dimethoxy-2-hydroxyiminopropionitrile)
To a flask having an internal volume of 100 ml equipped with a stirrer and a dropping funnel, 3.0 g (36 mmol) of 3-methoxyacrylonitrile, 9.0 g (63 mmol) of 25 mass% hydrogen chloride methanol solution and 15 ml of methanol were added. While stirring, 4.7 g (43 mmol) of n-butyl nitrite was slowly added dropwise to generate nitrosyl halide and n-butyl alcohol in the system (method (1) above) and reacted at room temperature for 26 hours. . After completion of the reaction, the reaction mixture was neutralized by adding saturated sodium hydrogen carbonate, and methanol was distilled off from the reaction solution under reduced pressure. The aqueous layer was extracted with ethyl acetate, the organic layer was taken out, washed with saturated brine, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was recrystallized from toluene to obtain 2.6 g of 3,3-dimethoxy-2-hydroxyiminopropionitrile (isolated yield: 50%) as a white solid. It was.
[0035]
Reference Example 1 (Synthesis of 5-amino-1-hydroxy-4-nitrosopyrazole hydrochloride)
Into a 100 ml flask equipped with a stirrer, a thermometer and a reflux condenser, 7.93 g (55 mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile synthesized in the same manner as in Example 1, 2- Hydroxyethylhydrazine (4.01 g, 50 mmol), ethanol (50 ml) and concentrated hydrochloric acid (7.60 g, 75 mmol) were added, and the mixture was reacted under reflux (76-79 ° C.) for 1 hour. After completion of the reaction, the reaction solution was concentrated under reduced pressure, 20 ml of toluene and 20 ml of isopropyl alcohol were added to the concentrate, and the mixture was stirred for 1 hour. The solution was then filtered, and the filtrate was dried at 40 ° C. under reduced pressure to obtain 6.85 g (isolation yield: 72%) of 5-amino-1-hydroxy-4-nitrosopyrazole hydrochloride as a yellow solid. .
The physical properties of 5-amino-1-hydroxy-4-nitrosopyrazole hydrochloride were as follows.
[0036]
Melting point: 164.8-166.6 ° C (dec.)
1 H-NMR (DMSO-d 6 , δ (ppm)); 3.65 to 4.13 (4H, m), 6.80 to 10.40 (5H, m) IR (KBr method, cm −1 ); 3290, 3063, 2635, 1670 , 1623, 1208, 1099, 1063, 1002, 716
[0037]
【The invention's effect】
According to the present invention, a novel 3,3-dialkoxy-2-hydroxyimino derivative and a production method thereof can be provided.

Claims (2)

一般式(1)
Figure 0003855686
(式中、R1及びR2は、同一又は異なっていても良く、炭素数1〜8のアルキル基を示し、R3は、シアノ基を示す。)
で示される3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体。
General formula (1)
Figure 0003855686
(In formula, R < 1 > and R < 2 > may be same or different, shows a C1-C8 alkyl group, and R < 3 > shows a cyano group.)
A 3,3-dialkoxy-2-hydroxyimino derivative represented by the formula:
アルコールの存在下、一般式(2)
Figure 0003855686
(式中、R3は、前記と同義であり、R4は、炭素数1〜4のアルキル基を示す。)
で示されるエノールエーテル化合物にニトロシルハライドを反応させることを特徴とする、請求項1記載の3,3-ジアルコキシ-2-ヒドロキシイミノ誘導体の製造法。
General formula (2) in the presence of alcohol
Figure 0003855686
(In the formula, R 3 has the same meaning as described above, and R 4 represents an alkyl group having 1 to 4 carbon atoms.)
A process for producing a 3,3-dialkoxy-2-hydroxyimino derivative according to claim 1, wherein a nitrosyl halide is reacted with the enol ether compound represented by formula (1).
JP2001176897A 2001-06-12 2001-06-12 3,3-dialkoxy-2-hydroxyimino derivative and process for producing the same Expired - Lifetime JP3855686B2 (en)

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JP2001176897A JP3855686B2 (en) 2001-06-12 2001-06-12 3,3-dialkoxy-2-hydroxyimino derivative and process for producing the same
EP02736058A EP1408025B1 (en) 2001-06-12 2002-06-12 3,3-dialkoxy-2-hydroxyiminopropionitriles, process for preparation thereof and process of preparing 5-amino -4-nitrosopyrazoles or salts thereof by the use of the same
US10/480,576 US7227032B2 (en) 2001-06-12 2002-06-12 3,3-dialkoxy-2-hydroxyiminopropionitriles, process for preparation thereof and process of preparing 5-amino-4-nitrosopyrazoles or salts thereof by the use of the same
PCT/JP2002/005827 WO2002100821A1 (en) 2001-06-12 2002-06-12 3,3-dialkoxy-2-hydroxyiminopropionitriles, process for preparation thereof and process of preparing 5-amino -4-nitrosopyrazoles or salts thereof by the use of the same
DE60223683T DE60223683T2 (en) 2001-06-12 2002-06-12 3,3-DIALKOXY-2-HYDROXYIMINOPROPIONIC ACIDITRILE, METHOD FOR THE PRODUCTION AND METHOD FOR THE PRODUCTION OF 5-AMINO-4-NITROSOPYRAZOLENE BZW. SALTS OF IT UNDER OPERATION OF THESE CONNECTIONS

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