JPH0478632B2 - - Google Patents
Info
- Publication number
- JPH0478632B2 JPH0478632B2 JP6915783A JP6915783A JPH0478632B2 JP H0478632 B2 JPH0478632 B2 JP H0478632B2 JP 6915783 A JP6915783 A JP 6915783A JP 6915783 A JP6915783 A JP 6915783A JP H0478632 B2 JPH0478632 B2 JP H0478632B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxymethylene
- alkali metal
- acid ester
- metal salt
- salt
- 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.)
- Expired
Links
- -1 alkali metal salt Chemical class 0.000 claims description 18
- 229910052783 alkali metal Inorganic materials 0.000 claims description 14
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 150000003217 pyrazoles Chemical class 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- NUGZBVBZIDWZAD-UHFFFAOYSA-N 1h-pyrazole-4-carbonitrile Chemical group N#CC=1C=NNC=1 NUGZBVBZIDWZAD-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000010813 internal standard method Methods 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 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
- QDSMOWYMYIABBZ-UHFFFAOYSA-N 2,2-dimethoxypropanenitrile Chemical compound COC(C)(OC)C#N QDSMOWYMYIABBZ-UHFFFAOYSA-N 0.000 description 1
- GPHPDHHIQSTHMT-UHFFFAOYSA-N 2-(dibutoxymethyl)-3-hydroxyprop-2-enenitrile Chemical compound CCCCOC(C(=CO)C#N)OCCCC GPHPDHHIQSTHMT-UHFFFAOYSA-N 0.000 description 1
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
- FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- WBDLSXCAFVEULB-UHFFFAOYSA-N acetonitrile;methylsulfinylmethane Chemical compound CC#N.CS(C)=O WBDLSXCAFVEULB-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 238000009835 boiling Methods 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- KACZQOKEFKFNDB-UHFFFAOYSA-N ethyl 1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1 KACZQOKEFKFNDB-UHFFFAOYSA-N 0.000 description 1
- GHNZTFJJBRPTQZ-UHFFFAOYSA-N ethyl 2-(diethoxymethyl)-3-hydroxyprop-2-enoate Chemical compound CCOC(OCC)C(=CO)C(=O)OCC GHNZTFJJBRPTQZ-UHFFFAOYSA-N 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
- 238000001914 filtration Methods 0.000 description 1
- RIKMMFOAQPJVMX-UHFFFAOYSA-N fomepizole Chemical compound CC=1C=NNC=1 RIKMMFOAQPJVMX-UHFFFAOYSA-N 0.000 description 1
- 229960004285 fomepizole Drugs 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229910000377 hydrazine sulfate Inorganic materials 0.000 description 1
- 239000012493 hydrazine sulfate Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- ORUCTBNNYKZMSK-UHFFFAOYSA-N methyl 1h-pyrazole-5-carboxylate Chemical compound COC(=O)C=1C=CNN=1 ORUCTBNNYKZMSK-UHFFFAOYSA-N 0.000 description 1
- KHQQDBIXHUJARJ-UHFFFAOYSA-N methyl 2,2-dimethoxypropanoate Chemical compound COC(=O)C(C)(OC)OC KHQQDBIXHUJARJ-UHFFFAOYSA-N 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
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 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
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、４−置換ピラゾール類、すなわち、
４−位にシアノ基の置換した４−ピラゾールカル
ボニトリル、あるいは４−位に低級アルコキシカ
ルボニル基の置換した４−ピラゾールカルボン酸
エステルの新規な製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 4-substituted pyrazoles, namely:
The present invention relates to a novel method for producing 4-pyrazolecarbonitrile substituted with a cyano group at the 4-position or 4-pyrazolecarboxylic acid ester substituted with a lower alkoxycarbonyl group at the 4-position.
本発明によつて製造される４−置換ピラゾール
類は、例えば医薬、農薬などの合成中間体として
有用な化合物である。 The 4-substituted pyrazoles produced according to the present invention are useful compounds, for example, as synthetic intermediates for pharmaceuticals, agricultural chemicals, and the like.
従来、４−ピラゾールカルボニトリルの製造法
としては、例えば、J.O.C28 2755（1963）に、３
−アミノ−２−シアノアクロレインとヒドラジン
をエタノール中で反応させる方法が開示されてい
る。しかしこの方法は、目的物の粗収率で65％と
低く、工業的に充分なものではない。また４−ピ
ラゾールカルボン酸エステルの製造法としては例
えばC.A.45−157d（1951）に、４−メチルピラゾ
ールをKMnO4で酸化し、次いでエルテル化する
方法が提案されているが、この方法も目的物の収
率が50％程度と極めて低い。 Conventionally, as a method for producing 4-pyrazole carbonitrile, for example, JOC 28 2755 (1963), 3
A method is disclosed in which -amino-2-cyanoacrolein and hydrazine are reacted in ethanol. However, this method has a low crude yield of 65% of the target product, and is not industrially sufficient. In addition, as a method for producing 4-pyrazole carboxylic acid ester, for example, CA45-157d (1951) proposes a method in which 4-methylpyrazole is oxidized with KMnO 4 and then eruterized, but this method also produces the desired product. The yield is extremely low at around 50%.
本発明者らは、４−位にシアノ基または４−位
に低級アルコキシカルボニル基の置換した４−置
換ピラゾール類の工業的に有利な製法を確立する
ことを目的とし、鋭意研究を行つた。その結果、
２−ヒドロキシメチレン−３，３−ジアルコキシ
プロパンニトリルのアルカリ金属塩、または２−
ヒドロキシメチレン−３，３−ジアルコキシプロ
ピオン酸エステルのアルカリ金属塩と、ヒドラジ
ンの鉱酸塩を反応させれば、その目的が達成され
ること、すなわち４−置換ピラゾール類が高収率
で製造されること、を知見し本発明を完成した。 The present inventors conducted extensive research with the aim of establishing an industrially advantageous method for producing 4-substituted pyrazoles substituted with a cyano group or a lower alkoxycarbonyl group at the 4-position. the result,
Alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile, or 2-
The reaction of the alkali metal salt of hydroxymethylene-3,3-dialkoxypropionic acid ester with the mineral acid salt of hydrazine achieves the objective, i.e., 4-substituted pyrazoles are produced in high yields. They discovered this and completed the present invention.
本発明の原料である２−ヒドロキシメチレン−
３，３−ジアルコキシプロパンニトリルのアルカ
リ金属塩の構造式は、次の一般式（）で表わす
ことができる。 2-Hydroxymethylene, the raw material of the present invention
The structural formula of the alkali metal salt of 3,3-dialkoxypropanenitrile can be represented by the following general formula ().
また２−ヒドロキシメチレン−３，３−ジアル
コキシプロピオン酸エステルのアルカリ金属塩の
構造式は、次の一般式（）で表わすことができ
る。 Further, the structural formula of the alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropionic acid ester can be represented by the following general formula ().
ただし一般式（）および（）において、
R1、R2およびR3は、メチル、エチル、プロピル、
ブチル、ペンチルなどの炭素数１〜５を有する低
級アルキル基を示し、R1とR2さらにはR3は同一
のアルキル基であつてもよく、相異なるアルキル
基であることもできる。また、一般式（）およ
び（）におけるＭは、ナトリウム、カリウムあ
るいはリチウムの如きアリカリ金属を示す。 However, in general formulas () and (),
R 1 , R 2 and R 3 are methyl, ethyl, propyl,
It represents a lower alkyl group having 1 to 5 carbon atoms such as butyl and pentyl, and R 1 and R 2 and even R 3 may be the same alkyl group or different alkyl groups. Furthermore, M in the general formulas () and () represents an alkali metal such as sodium, potassium or lithium.
これらの２−ヒドロキシメチレン−３，３−ジ
アルコキシプロパンニトリルのアルカリ金属塩、
および２−ヒドロキシメチレン−３，３−ジアル
コキシプロピオン酸エステルのアルカリ金属塩
は、公知の方法によつて合成することができる。
例えば、３，３−ジアルコキシプロパンニトリル
または、３，３−ジアルコキシプロピオン酸エス
テルを、アルカリ金属アルコラートの存在下に、
ギ酸エステルあるいは一酸化炭素の如きホルミル
化剤と０〜100℃の温度で反応させることによつ
て合成することができる。 These alkali metal salts of 2-hydroxymethylene-3,3-dialkoxypropanenitrile,
The alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropionic acid ester can be synthesized by a known method.
For example, 3,3-dialkoxypropanenitrile or 3,3-dialkoxypropionic acid ester in the presence of an alkali metal alcoholate,
It can be synthesized by reacting with a formylating agent such as formate or carbon monoxide at a temperature of 0 to 100°C.
本発明のもう一方の原料であるヒドラジンの鉱
酸塩としては、ヒドラジンの塩酸塩、硫酸塩、硝
酸塩、リン酸塩などを挙げることができる。これ
らヒドラジンの鉱酸塩は、余り多く使用すると副
反応生成物が多くなり、またその使用量が余り少
なすぎると、未反応の前記もう一方の原料が多く
残り、いずれも工業的に好ましくない。従つてそ
の使用量は、２−ヒドロキシメチレン−３，３−
ジアルコキシプロパンニトリルのアルカリ金属
塩、または２−ヒドロキシメチレン−３，３−ジ
メトキシプロピオン酸エステルのアルカリ金属塩
１モルに対して、通常0.1〜10モル、好ましくは
0.5〜５モルである。 Examples of the mineral salt of hydrazine, which is another raw material of the present invention, include hydrazine hydrochloride, sulfate, nitrate, and phosphate. If too much of these hydrazine mineral acid salts are used, side reaction products will increase, and if too little is used, a large amount of the other raw material will remain unreacted, both of which are industrially unfavorable. Therefore, the amount used is 2-hydroxymethylene-3,3-
Usually 0.1 to 10 mol, preferably 0.1 to 10 mol, preferably
The amount is 0.5 to 5 moles.
本発明の反応は、溶媒中で行われる。使用に供
される溶媒としては、反応に不活性なものであれ
ばいずれも有用である。その具体例としては、メ
タノール、エタノールー、プロパノール、ブタノ
ール、エチレングリコールなどのアルコール系溶
媒；ジエチルエーテル、ジメトキシエタン、ジオ
キサン、テトラヒドロフランなどのエーテル系溶
媒；ベンゼン、トルエン、キシレン、ヘキサン、
ヘプタン、シクロヘキサンなどの炭化水素系溶
媒；塩化メチレン、クロロホルム、四塩化炭素、
ジクロロエタンなどのハロゲン化炭化水素系溶
媒；酢酸メチル、酢酸エチル、酢酸ブチルなどの
エステル系溶媒；さらには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および水
などを例示することができる。これらの中でも、
特にアルコール系容媒、あるいはアルコール系溶
媒と他の溶媒との混合溶媒の使用が好ましい。 The reaction of the invention is carried out in a solvent. Any solvent that is inert to the reaction is useful. Specific examples include alcohol solvents such as methanol, ethanol, propanol, butanol, and ethylene glycol; ether solvents such as diethyl ether, dimethoxyethane, dioxane, and tetrahydrofuran; benzene, toluene, xylene, hexane,
Hydrocarbon solvents such as heptane and cyclohexane; methylene chloride, chloroform, carbon tetrachloride,
Examples include halogenated hydrocarbon solvents such as dichloroethane; ester solvents such as methyl acetate, ethyl acetate, and butyl acetate; further examples include acetonitrile dimethyl sulfoxide, dimethylformamide, and water. Among these,
In particular, it is preferable to use an alcoholic medium or a mixed solvent of an alcoholic solvent and another solvent.
本発明の反応は０〜100℃の温度で0.1〜10時間
行なうことで完結する。 The reaction of the present invention is completed by carrying out the reaction at a temperature of 0 to 100°C for 0.1 to 10 hours.
反応終了後、例えば過、濃縮、抽出、再結晶
あるいは、昇華などの操作を適宜採用することに
より、４−置換ピラゾール類を単離・精製するこ
とができる。 After the reaction is completed, the 4-substituted pyrazoles can be isolated and purified by appropriate operations such as filtration, concentration, extraction, recrystallization, or sublimation.
本発明において、原料として２−ヒドロキシメ
チレン−３，３−ジアルコキシプロパンニトリル
のアルカリ金属塩を用いた場合には、次の構造式
（）で表わされる４−ピラゾールカルボニトリ
ルを得ることができる。 In the present invention, when an alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile is used as a raw material, 4-pyrazolecarbonitrile represented by the following structural formula () can be obtained.
また原料として２−ヒドロキシメチレン−３，
３−ジアルコキシプロピオン酸エステルのアルカ
リ金属塩を用いた場合には、次の一般式（）で
表わされる４−ピラゾールカルボン酸エステルを
得ることができる。 In addition, 2-hydroxymethylene-3,
When an alkali metal salt of a 3-dialkoxypropionic acid ester is used, a 4-pyrazolecarboxylic acid ester represented by the following general formula () can be obtained.
ただし式中R3は、前記一般式（）における
R3に相当する。 However, R 3 in the formula is
Equivalent to R3 .
次に本発明の実施例を挙げる。なお各例中の目
的物の収率は、使用に供した２−ヒドロキシメチ
レン−３，３−ジアルコキシプロパンニトリルの
アルカリ金属塩、または２−ヒドロキシメチレン
−３，３−ジアルコキシプロピオン酸エステルの
アルカリ金属塩基準である。 Next, examples of the present invention will be described. The yield of the target product in each example is based on the alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile or the 2-hydroxymethylene-3,3-dialkoxypropionic acid ester used. Based on alkali metal salts.
実施例 １
２−ヒドロキシメチレン−３，３−ジアルコキ
シプロパンニトリルのナトリウム塩（純度91.6
％）10.0ｇ（55.5ミリモル）をメタノール60ｇに
溶解させた後、室温撹拌下にヒドラジンの塩酸塩
3.80ｇ（55.5ミリモル）を加え、室温で２時間撹
拌を行つた。次いで濃縮乾固し塩化メチレンで抽
出した。塩化メチレン溶液を濃縮すると、淡黄色
の粗結晶4.44ｇが得られた。ガスクロマトグラフ
イーで内部標準法により４−ピラゾールカルボニ
トリルを定量すると、この粗結晶の純度は93.5％
であつた。従つて、その収率は80.4％であつた。
この粗結晶を減圧下昇華精製すると、融点90〜
91.5℃の白色結晶が得られた。このものの1R、
NMR、MSは４−ピラゾールカルボニトリルに
一致した。Example 1 Sodium salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile (purity 91.6
%) 10.0 g (55.5 mmol) was dissolved in 60 g of methanol, and then hydrazine hydrochloride was dissolved under stirring at room temperature.
3.80 g (55.5 mmol) was added and stirred at room temperature for 2 hours. The mixture was then concentrated to dryness and extracted with methylene chloride. When the methylene chloride solution was concentrated, 4.44 g of pale yellow crude crystals were obtained. When 4-pyrazole carbonitrile was quantified by gas chromatography using the internal standard method, the purity of this crude crystal was 93.5%.
It was hot. Therefore, the yield was 80.4%.
When this crude crystal is purified by sublimation under reduced pressure, the melting point is 90~
White crystals at 91.5°C were obtained. 1R of this,
NMR and MS were consistent with 4-pyrazole carbonitrile.
実施例 ２
２−ヒドロキシメチレン−３，３−ジ−ｎ−ブ
トキシプロパンニトリルのナトリウム塩（純度
90.5％）2.50ｇ（9.1ミリモル）を水20mlに溶解さ
せた後、室温撹拌下にヒドラジンの硫酸塩1.18ｇ
（9.09ミリモル）を加え、室温で２時間撹拌を行
つた。次いで1N−NaOHにより反応液のpHを８
〜９に調整し塩化メチレンで抽出した。この塩化
メチレン層をガスクロマトグラフイーにて内部標
準法により定量した結果、４−ピラゾールカルボ
ニトリルが78.9％の収率で生成していることが確
認された。Example 2 Sodium salt of 2-hydroxymethylene-3,3-di-n-butoxypropanenitrile (purity
After dissolving 2.50 g (9.1 mmol) of 90.5%) in 20 ml of water, 1.18 g of hydrazine sulfate was added under stirring at room temperature.
(9.09 mmol) was added and stirred at room temperature for 2 hours. Then, the pH of the reaction solution was adjusted to 8 with 1N-NaOH.
-9 and extracted with methylene chloride. As a result of quantifying this methylene chloride layer using gas chromatography using an internal standard method, it was confirmed that 4-pyrazole carbonitrile was produced at a yield of 78.9%.
実施例 ３
２−ヒドロキシメチレン−３，３−ジエトキシ
プロピオン酸エチルのナトリウム塩（純度92.3
％）10.0ｇ（38.5ミリモル）をエタノール120ｇ
に溶解させた後、室温撹拌下にヒドラジンの塩酸
塩2.64ｇ（38.5ミリモル）を加え、室温で４時間
撹拌を行つた。次いで濃縮乾固し、水を加え無機
塩を溶解させた後、エチルエーテルで抽出した。
エーテル層を硫酸ナトリウムで乾燥した後、エー
テルを濃縮し次いで真空蒸留し、沸点136〜
139゜／３mmHgの留分3.97ｇを得た、このものの
1R、NMR、MSは、４−ピラゾールカルボン酸
エチルエステルに一致した。収率73.6％。Example 3 Sodium salt of ethyl 2-hydroxymethylene-3,3-diethoxypropionate (purity 92.3
%) 10.0g (38.5 mmol) to 120g of ethanol
After dissolving in the solution, 2.64 g (38.5 mmol) of hydrazine hydrochloride was added while stirring at room temperature, and the mixture was stirred at room temperature for 4 hours. The mixture was then concentrated to dryness, water was added to dissolve the inorganic salts, and the mixture was extracted with ethyl ether.
After drying the ether layer with sodium sulfate, the ether was concentrated and then vacuum distilled to a boiling point of 136~
3.97g of fraction of 139°/3mmHg was obtained from this product.
1R, NMR, and MS were consistent with 4-pyrazolecarboxylic acid ethyl ester. Yield 73.6%.
実施例 ４
原料として２−ヒドロキシメチレン−３，３−
ジメトキシプロパンニトリルのカリウム塩（純度
98.0％）1.68ｇ（9.09ミリモル）を用い、また反
応温度を約50℃に変えた他は、実施例２と同様の
操作で実験を行つた。その結果、４−ピラゾール
カルボニトリルが78.5％の収率で得られた。Example 4 2-hydroxymethylene-3,3- as a raw material
Potassium salt of dimethoxypropanenitrile (purity
An experiment was conducted in the same manner as in Example 2, except that 1.68 g (9.09 mmol) of 98.0%) was used and the reaction temperature was changed to about 50°C. As a result, 4-pyrazole carbonitrile was obtained with a yield of 78.5%.
実施例 ５
原料として２−ヒドロキシメチレン−３，３−
ジメトキシプロピオン酸メチルのカリウム塩（純
度93.6％）9.15ｇ（40.0ミリモル）を用い、また
反応温度を約50℃に変えた他は、実施例３と同様
の操作で実験を行つた。その結果、４−ピラゾー
ルカルボン酸メチルエステルが70.8％の収率で得
られた。Example 5 2-hydroxymethylene-3,3- as a raw material
An experiment was conducted in the same manner as in Example 3, except that 9.15 g (40.0 mmol) of potassium salt of methyl dimethoxypropionate (purity 93.6%) was used and the reaction temperature was changed to about 50°C. As a result, 4-pyrazolecarboxylic acid methyl ester was obtained with a yield of 70.8%.
Claims (1)
キシプロパンニトリルのアルカリ金属塩、または
２−ヒドロキシメチレン−３，３−ジアルコキシ
プロピオン酸エステルのアルカリ金属塩と、ヒド
ラジンの鉱酸塩を反応させることを特徴とする４
−置換ピラゾール類の製造法。1 Reacting an alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropanenitrile or an alkali metal salt of 2-hydroxymethylene-3,3-dialkoxypropionic acid ester with a mineral acid salt of hydrazine. Features 4
- Method for producing substituted pyrazoles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6915783A JPS59196868A (en) | 1983-04-21 | 1983-04-21 | Production of 4-substituted pyrazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6915783A JPS59196868A (en) | 1983-04-21 | 1983-04-21 | Production of 4-substituted pyrazole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59196868A JPS59196868A (en) | 1984-11-08 |
| JPH0478632B2 true JPH0478632B2 (en) | 1992-12-11 |
Family
ID=13394564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6915783A Granted JPS59196868A (en) | 1983-04-21 | 1983-04-21 | Production of 4-substituted pyrazole |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59196868A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19701277A1 (en) * | 1997-01-16 | 1998-07-23 | Bayer Ag | Process for the preparation of 1-alkyl-pyrazole-5-carboxylic acid esters |
-
1983
- 1983-04-21 JP JP6915783A patent/JPS59196868A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59196868A (en) | 1984-11-08 |
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