JPH01156963A - Production of 1-substituted 5-aminopyrazole - Google Patents
Production of 1-substituted 5-aminopyrazoleInfo
- Publication number
- JPH01156963A JPH01156963A JP24087088A JP24087088A JPH01156963A JP H01156963 A JPH01156963 A JP H01156963A JP 24087088 A JP24087088 A JP 24087088A JP 24087088 A JP24087088 A JP 24087088A JP H01156963 A JPH01156963 A JP H01156963A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- formula
- aminopyrazole
- expressed
- group
- 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.)
- Granted
Links
- -1 1-substituted 5-aminopyrazole Chemical class 0.000 title claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 abstract description 9
- 239000011707 mineral Substances 0.000 abstract description 9
- 150000003839 salts Chemical class 0.000 abstract description 9
- 239000002904 solvent Substances 0.000 abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000006227 byproduct Substances 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 abstract description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 abstract description 2
- 239000003125 aqueous solvent Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- JJXWKXZOHOUFCX-UHFFFAOYSA-N methylhydrazine;hydrate Chemical compound O.CNN JJXWKXZOHOUFCX-UHFFFAOYSA-N 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 4
- 239000002253 acid Substances 0.000 abstract 2
- JESRNIJXVIFVOV-UHFFFAOYSA-N 2-methylpyrazol-3-amine Chemical compound CN1N=CC=C1N JESRNIJXVIFVOV-UHFFFAOYSA-N 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 abstract 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- IPCRTSDORDQHRO-DUXPYHPUSA-N (e)-3-methoxyprop-2-enenitrile Chemical compound CO\C=C\C#N IPCRTSDORDQHRO-DUXPYHPUSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- GBHCABUWWQUMAJ-UHFFFAOYSA-N 2-hydrazinoethanol Chemical compound NNCCO GBHCABUWWQUMAJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001424 substituent group Chemical group 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- KJDJPXUIZYHXEZ-UHFFFAOYSA-N hydrogen sulfate;methylaminoazanium Chemical compound CN[NH3+].OS([O-])(=O)=O KJDJPXUIZYHXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- SFKTYEXKZXBQRQ-UHFFFAOYSA-J thorium(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Th+4] SFKTYEXKZXBQRQ-UHFFFAOYSA-J 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［発明の目的］
（産業上の利用分野）
本発明は、ｌ−置換５−アミノピラゾールの製法に関す
る。DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] (Industrial Field of Application) The present invention relates to a method for producing l-substituted 5-aminopyrazoles.
（従来の技術及びその問題点）
ｌ−置換５−アミノピラゾールは、医薬、農薬等の合成
中間体として広く利用されている。(Prior art and its problems) l-substituted 5-aminopyrazoles are widely used as synthetic intermediates for pharmaceuticals, agricultural chemicals, and the like.
アミノピラゾール類の製法は、種々の方法が知られてい
るが、これらの方法をｌ−置換５−アミノピラゾールの
製造にそのまま適用すると、目的とする１−置換５−ア
ミノピラゾール以外に副生成物であるｌ−置換３−アミ
ノピラゾールが多量に混在してしまう。Various methods are known for producing aminopyrazoles, but if these methods are directly applied to the production of 1-substituted 5-aminopyrazoles, by-products will be produced in addition to the desired 1-substituted 5-aminopyrazoles. A large amount of l-substituted 3-aminopyrazole is mixed in.
ｌ−置換５−アミノピラゾールの製法としては、β−ジ
アルキルアミノアクリロニトリルとモノ置換ヒドラジン
とを反応させる方法が知られている（西独特許公開第２
１４１７００号公報、参照）。As a method for producing l-substituted 5-aminopyrazole, a method is known in which β-dialkylaminoacrylonitrile and monosubstituted hydrazine are reacted (West German Patent Publication No. 2).
141700, see).
しかしながら、この方法は、原料として用いるβ−ジア
ルキルアミノアクリロニトリルの供給が困難であり、収
率も充分なものとはいえない。However, in this method, it is difficult to supply β-dialkylaminoacrylonitrile used as a raw material, and the yield cannot be said to be sufficient.
そこで、本発明者らは、容易に供給できる原料から、好
収率で目的物であるｌ−置換５−アミノピラゾールを製
造できる１−置換５−アミノピラゾールの製法を見出す
べく鋭意研究を重ねた結果、本発明を完成するに至った
。Therefore, the present inventors conducted extensive research in order to find a method for producing 1-substituted 5-aminopyrazole that can produce the target product, 1-substituted 5-aminopyrazole, in good yield from easily supplied raw materials. As a result, the present invention was completed.
［発明の構成］
（問題点を解決するための手段及び作用）本発明は、
次式（Ｉ）：
Ｒ１ＯＣＨ＝ＣＨＣＮ （Ｉ）（式中、Ｒ
１は低級アルキル基を表す。）で示される３−アルコキ
シアクリロニトリルと次式（ＩＩ）：
Ｒ２ＮＨＮＨ，（ＩＩ）
（式中、Ｒ２は置換されていてもよい低級アルキル基又
はアリール基を表す。）
で示されるモノ置換ヒドラジンとを反応させることを特
徴とする
次式（ＩＩＩ）：
（式中、Ｒ２は前記と同義である。）
で示されるｌ−置換５−アミノピラゾールの製法に関す
るものである。[Structure of the invention] (Means and effects for solving the problems) The present invention provides the following formula (I): R1OCH=CHCN (I) (wherein, R
1 represents a lower alkyl group. ) and a monosubstituted hydrazine represented by the following formula (II): R2NHNH, (II) (wherein, R2 represents an optionally substituted lower alkyl group or aryl group). The present invention relates to a method for producing l-substituted 5-aminopyrazole represented by the following formula (III): (wherein, R2 has the same meaning as above).
前記式（Ｉ ’）、（ＩＩ）及び（ＩＩＩ ）において
、Ｒ１及びＲ２で表される低級アルキル基は、炭素数１
〜５のアルキル基であり、例えばメチル基、エチル基、
プロピル基、イソプロピル基、ブチル基、イソブチル基
、５ｅＣ−ブチル基、ｔｅｒｔ−ブチル基、ペンチル基
等が挙げられる。また、Ｒ２で表される低級アルキル基
は、不活性な置換基で置換されていてもよく、かかる置
換低級アルキル基としては、例えばヒドロキシエチル基
、クロロエチル基、ニトロプロピル基等が挙げられる。In the formulas (I'), (II) and (III), the lower alkyl groups represented by R1 and R2 have a carbon number of 1
~5 alkyl groups, such as methyl group, ethyl group,
Examples include propyl group, isopropyl group, butyl group, isobutyl group, 5eC-butyl group, tert-butyl group, pentyl group, and the like. Further, the lower alkyl group represented by R2 may be substituted with an inert substituent, and examples of such substituted lower alkyl groups include hydroxyethyl group, chloroethyl group, and nitropropyl group.
前記式（Ｉｆ）において、Ｒ２で表されるアリールは、
不活性な置換基で置換されてい−Ｃ６よ。、フェニル基
であり、例えばフェニル基、トシル基、クロロフェニル
基、メトキシフェニル基、イソプロピルフェニル基、キ
シリル基、ニトロフェニル基、シアノフェニル基等が挙
げられる。In the formula (If), the aryl represented by R2 is
-C6 substituted with an inert substituent. , a phenyl group, such as a phenyl group, a tosyl group, a chlorophenyl group, a methoxyphenyl group, an isopropylphenyl group, a xylyl group, a nitrophenyl group, a cyanophenyl group, and the like.
前記式（ｎ）で示されるモノ置換ヒドラジンは、遊離の
もの、抱水ヒドラジン、鉱酸塩、例えば塩酸塩、硫酸塩
、硝酸塩、リン酸塩のいずれを用いてもよい。The monosubstituted hydrazine represented by the formula (n) may be free, hydrated hydrazine, or a mineral salt such as a hydrochloride, sulfate, nitrate, or phosphate.
モノ置換ヒドラジンの使用量は、３−アルコキシアクリ
ロニトリル１モルに対し、通常１モル以上、好ましくは
１〜５モルである。The amount of monosubstituted hydrazine used is usually 1 mol or more, preferably 1 to 5 mol, per 1 mol of 3-alkoxyacrylonitrile.
本反応は、モノ置換ヒドラジンとして鉱酸塩以外を用い
る場合は、無溶媒でもよい。溶媒を用いる場合は、反応
に不活性な溶媒であれば、如何なるものを用いてもよい
。かかる溶媒としては、例えば、メタノール、エタノー
ル、プロパツール、ブタノール、エチレングリコール等
のアルコール系溶媒ニジエチルエーテル、イソプロピル
エーテル、ジメトキシエタン、ジオキサン、テトラヒド
ロフラン等のエーテル系溶媒：ベンゼン、トルエン、キ
シレン、ヘキサン、ヘプタン、シクロヘキサン等の炭化
水素系溶媒：塩化メチレン、クロロホルム、四塩化炭素
、ジクロロエタン等のハロゲン化炭化水素系溶媒：酢酸
メチル、酢酸エチル、酢酸ブチル等のエステル系溶媒：
並びにアセトニトリル、ジメチルスルホキシド、ジメチ
ルホルムアミド及び水等が挙げられる。これらのうち、
水、アルコール系溶媒、及びその混合溶媒が特に好まし
い。This reaction may be carried out without a solvent if a monosubstituted hydrazine other than a mineral salt is used. When using a solvent, any solvent may be used as long as it is inert to the reaction. Such solvents include, for example, alcohol solvents such as methanol, ethanol, propatool, butanol, and ethylene glycol; ether solvents such as diethyl ether, isopropyl ether, dimethoxyethane, dioxane, and tetrahydrofuran; benzene, toluene, xylene, hexane; Hydrocarbon solvents such as heptane and cyclohexane: Halogenated hydrocarbon solvents such as methylene chloride, chloroform, carbon tetrachloride, and dichloroethane; Ester solvents such as methyl acetate, ethyl acetate, and butyl acetate:
Also, acetonitrile, dimethylsulfoxide, dimethylformamide, water and the like can be mentioned. Of these,
Particularly preferred are water, alcoholic solvents, and mixed solvents thereof.
モノ置換ヒドラジンとして鉱酸塩を用いる場合は、鉱酸
塩が不溶な溶媒は使用できない。従って、水性溶媒が好
ましい６
本発明において、反応は、塩基性領域（特にｐＨ８以上
）で行うことが好ましい。反応を酸性領域で行うと副生
成物であるｌ−置換３−アミノ □ピラゾールが混在
してしまう。従って、モノ置換ヒドラジンとして鉱酸塩
を用いる場合は、鉱酸塩水溶液が酸性であるため、この
まま用いたのでは選択性が悪くなる。それゆえ、例えば
、水酸化すトリウム、水酸化カリウム等の水酸化アルカ
リの水溶液によって、鉱酸塩水溶液のｐＨを８以上に調
整することが好ましい。When using a mineral salt as the monosubstituted hydrazine, a solvent in which the mineral salt is insoluble cannot be used. Therefore, an aqueous solvent is preferred 6 In the present invention, the reaction is preferably carried out in a basic region (particularly at pH 8 or higher). If the reaction is carried out in an acidic region, the by-product l-substituted 3-amino □pyrazole will be present. Therefore, when a mineral salt is used as the monosubstituted hydrazine, the mineral salt aqueous solution is acidic, so if used as is, the selectivity will be poor. Therefore, it is preferable to adjust the pH of the mineral salt aqueous solution to 8 or higher using, for example, an aqueous solution of an alkali hydroxide such as thorium hydroxide or potassium hydroxide.
反応は、室温程度の温和な条件でも進行するが、加熱す
るか、反応により生成するアルコールを留去することに
より反応の進行を促進することができる。従って、反応
温度は、３０〜１００℃が好ましい。Although the reaction proceeds under mild conditions at room temperature, the reaction can be accelerated by heating or by distilling off the alcohol produced by the reaction. Therefore, the reaction temperature is preferably 30 to 100°C.
反応終了後は、濃縮、抽出、蒸留、再結晶等の通常の分
離操作により、目的物を単離・生成することができる。After the reaction is completed, the target product can be isolated and produced by conventional separation operations such as concentration, extraction, distillation, and recrystallization.
（発明の実施例）
以下、実施例及び比較例により本発明を更に詳細に説明
するが、これらの実施例は本発明の範囲を何ら制限する
ものではない。(Examples of the Invention) Hereinafter, the present invention will be explained in more detail with reference to Examples and Comparative Examples, but these Examples are not intended to limit the scope of the present invention in any way.
実施例１
冷却管、温度計を備えた３００ｍ１フラスコに３−メト
キシアクリロニトリル３３．２ｇ、水１３６．５ｇ及び
３５％抱水メチルヒドラジン６３．１ｇを仕込み、撹拌
し、９０℃まで徐々に界温し、３時間還流した。その時
のｐＨは９であった。その液を冷却し、液体クロマトグ
ラフィーにて分析したところ、Ｉ−メチル−５−アミノ
ピラゾール１３．４％、■−メチルー３−アミノピラゾ
ール０．３３％を含んでいた。Example 1 33.2 g of 3-methoxyacrylonitrile, 136.5 g of water, and 63.1 g of 35% methylhydrazine hydrate were placed in a 300 ml flask equipped with a condenser and a thermometer, stirred, and gradually warmed to 90°C. , and refluxed for 3 hours. The pH at that time was 9. When the liquid was cooled and analyzed by liquid chromatography, it was found to contain 13.4% of I-methyl-5-aminopyrazole and 0.33% of -methyl-3-aminopyrazole.
比較例１
実施例１の装置に３−メトキシアクリロニトリル３３．
２ｇ、水１２９．６ｇ及びメチルヒドラジン硫酸塩７０
ｇを仕込み、撹拌し、９０℃まで徐々に昇温し、３時間
還流した。その時のｐＨは４であった。その液を冷却し
、液体クロマトグラフィーにて分析したところ、ｌ−メ
チル−５−アミノピラゾールｌ００５％、■−メチルー
３−アミノビラゾ〜ル４．５％を含んでいた。Comparative Example 1 3-methoxyacrylonitrile 33.
2g, water 129.6g and methylhydrazine sulfate 70g
g was charged, stirred, and gradually heated to 90°C, and refluxed for 3 hours. The pH at that time was 4. When the liquid was cooled and analyzed by liquid chromatography, it was found to contain 1005% of l-methyl-5-aminopyrazole and 4.5% of -methyl-3-aminopyrazole.
実施例２
実施例１の装置に３−メトキシアクリロニトリル３３．
２ｇ、水２１８．８ｇ及びフェニルヒドラジン５１．８
ｇを仕込み、撹拌し、９０〜１００’Ｃに昇温し、３時
間還流した。その時のｐ［（は８．５であった。その液
を冷却し、液体クロマトグラフィーにて分析したところ
、１−フェニル−５−アミノピラゾール１８．５％、■
−フェニルー３−アミノピラゾール０．５５％を含んで
いた。Example 2 3-methoxyacrylonitrile 33.
2g, water 218.8g and phenylhydrazine 51.8g
g was charged, stirred, heated to 90-100'C, and refluxed for 3 hours. At that time, p
- Phenyl-3-aminopyrazole 0.55%.
実施例３
実施例１の装置に３−メトキシアクリロニトリル３３．
２ｇ、トルエン１３２ｇ及び８０％抱水２−ヒドロキシ
エチルヒドラジン４４．１ｇを仕込み、撹拌し、９０°
Ｃまて徐々に昇温し、４時間還流した。その時のｐＨは
９であった。その液を冷却し、液体クロマトグラフィー
にて分析したところ、１−（２−ヒドロキシエチル）−
５−アミノピラゾール４２．２ｇを含んでいた。また、
■−（２−ヒドロキシエチル）−３−アミノピラゾール
は検出されなかった。Example 3 3-methoxyacrylonitrile 33.
2g of toluene, 132g of toluene, and 44.1g of 80% hydrated 2-hydroxyethylhydrazine were charged, stirred, and heated at 90°.
The temperature was gradually raised to 50°C, and the mixture was refluxed for 4 hours. The pH at that time was 9. When the liquid was cooled and analyzed by liquid chromatography, it was found that 1-(2-hydroxyethyl)-
It contained 42.2 g of 5-aminopyrazole. Also,
(2)-(2-hydroxyethyl)-3-aminopyrazole was not detected.
実施例４
実施例１の装置に３−メトキシアクリロニトリル３３．
２ｇ、水１３２ｇ及び８０％抱水２−ヒドロキシエチル
ヒドラジン４４．１ｇを仕込み、撹拌し、９０°Ｃまで
徐々に昇渇し、３時間還流した。その時のｐＨは８．５
であった。その液を冷却し、液体クロマトグラフィーに
て分析したところ、■−（２−ヒドロキシエチル）−５
−アミノピラゾール４３．２ｇを含んでいた。また、■
−（２−ヒドロキシエチル）−３−アミノピラゾールは
検出されなかった。Example 4 3-methoxyacrylonitrile 33.
2g of water, 132g of water, and 44.1g of 80% hydrated 2-hydroxyethylhydrazine were charged, stirred, gradually heated to 90°C, and refluxed for 3 hours. The pH at that time was 8.5
Met. When the liquid was cooled and analyzed by liquid chromatography, it was found that ■-(2-hydroxyethyl)-5
- Contained 43.2 g of aminopyrazole. Also,■
-(2-hydroxyethyl)-3-aminopyrazole was not detected.
［発明の効果］
本発明によれば、容易に供給できる原料がら、目的とす
るｌ−置換５−アミノピラゾールを選択的に製造するこ
とができる。[Effects of the Invention] According to the present invention, the desired l-substituted 5-aminopyrazole can be selectively produced from easily supplied raw materials.
Claims (1)
３−アルコキシアクリロニトリルと次式（II）： Ｒ＿２ＮＨＮＨ＿２（II） （式中、Ｒ＿２は置換されていてもよい低級アルキル基
又はアリール基を表す。） で示されるモノ置換ヒドラジンとを反応させることを特
徴とする 次式（III）： ▲数式、化学式、表等があります▼（III） （式中、Ｒ＿２は前記と同義である。） で示される１−置換５−アミノピラゾールの製法。[Claims] 3-alkoxyacrylonitrile represented by the following formula (I): R_1OCH=CHCN (I) (in the formula, R_1 represents a lower alkyl group) and the following formula (II): R_2NHNH_2(II) ( (In the formula, R_2 represents an optionally substituted lower alkyl group or aryl group.) The following formula (III) is characterized by reacting with a monosubstituted hydrazine represented by ▼(III) (In the formula, R_2 has the same meaning as above.) A method for producing 1-substituted 5-aminopyrazole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24087088A JPH0662578B2 (en) | 1987-09-29 | 1988-09-28 | Process for producing 1-substituted 5-aminopyrazole |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24251587 | 1987-09-29 | ||
| JP62-242515 | 1987-09-29 | ||
| JP24087088A JPH0662578B2 (en) | 1987-09-29 | 1988-09-28 | Process for producing 1-substituted 5-aminopyrazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01156963A true JPH01156963A (en) | 1989-06-20 |
| JPH0662578B2 JPH0662578B2 (en) | 1994-08-17 |
Family
ID=26534976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24087088A Expired - Fee Related JPH0662578B2 (en) | 1987-09-29 | 1988-09-28 | Process for producing 1-substituted 5-aminopyrazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0662578B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294564A (en) * | 2015-12-08 | 2016-02-03 | 山东铂源药业有限公司 | Synthetic method of 5-amino-1-(2-hydroxyethyl)pyrazole |
-
1988
- 1988-09-28 JP JP24087088A patent/JPH0662578B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105294564A (en) * | 2015-12-08 | 2016-02-03 | 山东铂源药业有限公司 | Synthetic method of 5-amino-1-(2-hydroxyethyl)pyrazole |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0662578B2 (en) | 1994-08-17 |
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