JPH06220019A - Production of 2-hydroxy-3,5-dinitropyridine compounds - Google Patents
Production of 2-hydroxy-3,5-dinitropyridine compoundsInfo
- Publication number
- JPH06220019A JPH06220019A JP3263193A JP3263193A JPH06220019A JP H06220019 A JPH06220019 A JP H06220019A JP 3263193 A JP3263193 A JP 3263193A JP 3263193 A JP3263193 A JP 3263193A JP H06220019 A JPH06220019 A JP H06220019A
- Authority
- JP
- Japan
- Prior art keywords
- sulfuric acid
- hydroxy
- acid
- fuming
- mixture
- 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
- KSZZJOXNRQKULB-UHFFFAOYSA-N 3,5-dinitro-1h-pyridin-2-one Chemical class OC1=NC=C([N+]([O-])=O)C=C1[N+]([O-])=O KSZZJOXNRQKULB-UHFFFAOYSA-N 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- UBQKCCHYAOITMY-UHFFFAOYSA-N 2-hydroxy-pyridine Natural products OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims abstract description 32
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 17
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000000802 nitrating effect Effects 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000002253 acid Substances 0.000 abstract description 17
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 10
- 239000007789 gas Substances 0.000 abstract description 7
- -1 2-hydroxy-3,5-dinitropyridine compound Chemical class 0.000 abstract description 5
- 238000005187 foaming Methods 0.000 abstract description 5
- 230000020169 heat generation Effects 0.000 abstract description 5
- TXKMVPPZCYKFAC-UHFFFAOYSA-N disulfur monoxide Inorganic materials O=S=S TXKMVPPZCYKFAC-UHFFFAOYSA-N 0.000 abstract description 3
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical compound S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- ZXVONLUNISGICL-UHFFFAOYSA-N 4,6-dinitro-o-cresol Chemical group CC1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O ZXVONLUNISGICL-UHFFFAOYSA-N 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- 239000013078 crystal Substances 0.000 description 3
- 230000005484 gravity Effects 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RFSIFTKIXZLPHR-UHFFFAOYSA-N 3,5-dinitropyridine Chemical compound [O-][N+](=O)C1=CN=CC([N+]([O-])=O)=C1 RFSIFTKIXZLPHR-UHFFFAOYSA-N 0.000 description 2
- BOAFCICMVMFLIT-UHFFFAOYSA-N 3-nitro-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1[N+]([O-])=O BOAFCICMVMFLIT-UHFFFAOYSA-N 0.000 description 2
- YBDRFJXGJQULGH-UHFFFAOYSA-N 4-methyl-1h-pyridin-2-one Chemical compound CC1=CC=NC(O)=C1 YBDRFJXGJQULGH-UHFFFAOYSA-N 0.000 description 2
- XKWSQIMYNVLGBO-UHFFFAOYSA-N 5-nitro-1h-pyridin-2-one Chemical compound OC1=CC=C([N+]([O-])=O)C=N1 XKWSQIMYNVLGBO-UHFFFAOYSA-N 0.000 description 2
- JEAVIRYCMBDJIU-UHFFFAOYSA-N 6-methyl-1h-pyridin-2-one Chemical compound CC1=CC=CC(O)=N1 JEAVIRYCMBDJIU-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RUPDGJAVWKTTJW-UHFFFAOYSA-N 2,3-dinitropyridine Chemical class [O-][N+](=O)C1=CC=CN=C1[N+]([O-])=O RUPDGJAVWKTTJW-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical class [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- OBINQXYDORXSKL-UHFFFAOYSA-N 3,5-dihydroxy-1h-pyridin-2-one Chemical class OC1=CNC(=O)C(O)=C1 OBINQXYDORXSKL-UHFFFAOYSA-N 0.000 description 1
- FSPIBFKGESGOLU-UHFFFAOYSA-N 4,6-dimethyl-1h-pyridin-2-one Chemical compound CC1=CC(C)=NC(O)=C1 FSPIBFKGESGOLU-UHFFFAOYSA-N 0.000 description 1
- NCXXHBCMRXSTLW-UHFFFAOYSA-N 4-methyl-3,5-dinitro-1h-pyridin-2-one Chemical compound CC=1C([N+]([O-])=O)=CNC(=O)C=1[N+]([O-])=O NCXXHBCMRXSTLW-UHFFFAOYSA-N 0.000 description 1
- WCKGWNSUHCHSRW-UHFFFAOYSA-N 4-propyl-1h-pyridin-2-one Chemical compound CCCC=1C=CNC(=O)C=1 WCKGWNSUHCHSRW-UHFFFAOYSA-N 0.000 description 1
- UEYCHQJYLDEMEZ-UHFFFAOYSA-N 6-methyl-3,5-dinitro-1h-pyridin-2-one Chemical compound CC=1NC(=O)C([N+]([O-])=O)=CC=1[N+]([O-])=O UEYCHQJYLDEMEZ-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 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
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000007788 liquid Substances 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
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は２−ヒドロキシ−３，５
−ジニトロピリジン類の製造法に関する。２−ヒドロキ
シ−３，５−ジニトロピリジン類は酸化染料及び医農薬
の中間体として極めて重要な化合物である。The present invention relates to 2-hydroxy-3,5
-A method for producing dinitropyridines. 2-Hydroxy-3,5-dinitropyridines are extremely important compounds as oxidation dyes and intermediates for medical and agricultural chemicals.
【０００２】[0002]
【従来の技術】従来、２−ヒドロキシ−３，５−ニトロ
ピリジン類の製造法としては、例えば次のものが知られ
ている。 （１）まず反応温度０℃で２−ヒドロキシ−５−ニトロ
ピリジンを発煙硝酸と４０％発煙硫酸との混酸と反応さ
せ、次いで７０℃に昇温して反応させる方法（Ｊ．Ｐｈ
ａｒｍ．Ｓｏｃ．Ｊａｐａｎ，６９，４０９−１１（１
９４９））。収率＝６７％。 （２）反応温度８０〜９０℃で２−ヒドロキシ−３−ニ
トロピリジンを発煙硝酸と４０％発煙硫酸との混酸と反
応させる方法（Ｒｏｃｚｎｉｋｉ Ｃｈｅｍ．，３３，
８３１ー４（１９５９））。収率＝５０％。 （３）反応温度４０℃以下で２−ヒドロキシピリジンを
発煙硝酸と濃硫酸との混酸と反応させる方法（Ａｎｇｅ
ｗ．Ｃｈｅｍ．，４９，４８６−９（１９３６））。収
率＝約６％。 （４）まず反応温度０℃で２−ヒドロキシピリジンを発
煙硝酸と２０％発煙硫酸との混酸と反応させ、次いでを
８０〜８５℃に昇温して反応させる方法（Ｇａｚｚ．Ｃ
ｈｉｍ．Ｉｔａｌ．，９３，Ｎｏ．１−２，６５−７２
（１９６３））。収率＝５０％。2. Description of the Related Art Conventionally, for example, the following methods are known as methods for producing 2-hydroxy-3,5-nitropyridines. (1) A method in which 2-hydroxy-5-nitropyridine is first reacted with a mixed acid of fuming nitric acid and 40% fuming sulfuric acid at a reaction temperature of 0 ° C., and then the temperature is raised to 70 ° C. to react (J. Ph.
arm. Soc. Japan, 69, 409-11 (1
949)). Yield = 67%. (2) A method of reacting 2-hydroxy-3-nitropyridine with a mixed acid of fuming nitric acid and 40% fuming sulfuric acid at a reaction temperature of 80 to 90 ° C. (Roczniki Chem., 33,
834-1 (1959)). Yield = 50%. (3) A method of reacting 2-hydroxypyridine with a mixed acid of fuming nitric acid and concentrated sulfuric acid at a reaction temperature of 40 ° C. or lower (Ange
w. Chem. , 49, 486-9 (1936)). Yield = about 6%. (4) A method in which 2-hydroxypyridine is first reacted with a mixed acid of fuming nitric acid and 20% fuming sulfuric acid at a reaction temperature of 0 ° C., and then the temperature is raised to 80 to 85 ° C. to react (Gazz. C.
him. Ital. , 93, No. 1-2, 65-72
(1963)). Yield = 50%.
【０００３】[0003]
【本発明が解決しょうとする課題】前記（１）の方法
は、２−ヒドロキピリジンから出発する高価な２−ヒド
ロキシ−５−ニトロピリジンを原料として用い、さらに
０℃で反応した後、７０℃迄昇温すると、反応液が著し
い発泡と発熱を伴うため、安全性が重要視される工業的
製法としては不利である。前記（２）の方法は、前記
（１）と同様に原料の２−ヒドロキシ−３−ニトロピリ
ジンが高価であり、収率も５０％と充分なものではない
ため、工業的製法としては好ましくない。前記（３）の
方法は、２−ヒドロキシピリジンに対する２−ヒドロキ
シ−３，５−ジニトロピリジンの収率が約６％と極めて
低く、工業的に方法ではない。また、前記（４）の方法
は、２−ヒドロキシピリジンに対する２−ヒドロキシ−
３，５−ジニトロピリジンの収率が約５０％で工業的に
は満足できるものではない。さらに、０℃で反応した
後、８０℃以上に昇温すると、発煙硝酸と発煙硫酸から
発生する酸化窒素ガス及び酸化硫黄ガスによる反応液の
著しい発泡と発熱をともなうため、安全性が重要視され
る工業的製法としては不利である。The method (1) is carried out by using expensive 2-hydroxy-5-nitropyridine starting from 2-hydroxypyridine as a raw material, further reacting at 0 ° C, and then 70 ° C. When the temperature is raised up to this point, the reaction solution is accompanied by remarkable foaming and heat generation, which is disadvantageous as an industrial production method where safety is important. The method (2) is not preferable as an industrial production method because the raw material 2-hydroxy-3-nitropyridine is expensive and the yield is not sufficient at 50% as in the case (1). . The method (3) is not an industrial method because the yield of 2-hydroxy-3,5-dinitropyridine based on 2-hydroxypyridine is extremely low at about 6%. In addition, the method of (4) above is 2-hydroxy- for 2-hydroxypyridine.
The yield of 3,5-dinitropyridine is about 50%, which is not industrially satisfactory. Furthermore, when the temperature is raised to 80 ° C or higher after the reaction at 0 ° C, the reaction liquid is significantly foamed and exothermic due to the nitric oxide gas and the sulfur oxide gas generated from fuming nitric acid and fuming sulfuric acid, so safety is important. It is disadvantageous as an industrial manufacturing method.
【０００４】[0004]
【課題を解決するための手段】本発明者等は、上記従来
方法の欠点を解決すべく鋭意研究を行なった結果、反応
温度６０℃以上で２−ヒドロキシピリジン類にニトロ化
剤を供給しながら２−ヒドロキシピリジン類をジニトロ
化すると、従来法に比べて、高収率で２−ヒドロキシ−
３，５−ジニトロピリジン類を製造できること、さら
に、ニトロ化剤として発煙硝酸と発煙硝酸との混酸を用
いても、反応液の発熱と酸化窒素ガス及び酸化硫黄ガス
による発泡が、混酸の供給速度でコントロールでき、穏
やかな状態で反応操作ができることを見出し、本発明を
完成するに至った。Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the drawbacks of the above conventional methods, and as a result, while supplying a nitrating agent to 2-hydroxypyridines at a reaction temperature of 60 ° C. or higher. When 2-nitropyridines are dinitrated, 2-hydroxy-
It is possible to produce 3,5-dinitropyridines. Furthermore, even when a fuming nitric acid and a fuming nitric acid mixed acid are used as nitrating agents, heat generation of the reaction solution and foaming by nitric oxide gas and sulfur oxide gas cause a mixed acid supply rate. It was found that the reaction can be controlled by the method and the reaction operation can be performed in a gentle state, and the present invention has been completed.
【０００５】すなわち、本発明は、一般式（１）：That is, the present invention has the general formula (1):
【化３】 （式中、Ｒ1およびＲ2はいずれも水素原子又は低級アル
キル基を意味する）で表される２−ヒドロキシピリジン
類をジニトロ化して一般式（２）：[Chemical 3] (In the formula, R 1 and R 2 each represent a hydrogen atom or a lower alkyl group), and dihydroxylated 2-hydroxypyridines to give general formula (2):
【化４】 （式中、Ｒ1およびＲ2は前記に同じ）で表される２−ヒ
ドロキシ−３，５−ジニトロピリジン類を製造するにあ
たり、２−ヒドロキシピリジン類にニトロ化剤を供給し
ながら、反応温度６０℃以上でジニトロ化することを特
徴とする２−ヒドロキシ−３，５−ジニトロピリジン類
の製造法を提供するものである。[Chemical 4] (In the formula, R 1 and R 2 are the same as above) In producing 2-hydroxy-3,5-dinitropyridines, a reaction temperature is supplied to the 2-hydroxypyridines while supplying a nitrating agent. The present invention provides a method for producing 2-hydroxy-3,5-dinitropyridines, which comprises dinitration at 60 ° C or higher.
【０００６】本発明をさらに詳しく説明する。一般式
（１）および（２）おいてＲ1およびＲ2で示される低級
アルキル基としては、メチル基、エチル基、プロピル
基、ブチル基等が挙げられる。本発明の出発原料である
一般式（１）で示される２−ヒドロキシピリジン類（以
下、２−ヒドロキシピリジン類（１）という）として
は、２−ヒドロキシピリジン、２−ヒドロキシ−４−メ
チルピリジン、２−ヒドロキシ−４−プロピルピリジ
ン、２−ヒドロキシ−６−メチルピリジン、２−ヒドロ
キシ−４，６−ジメチルピリジン等が挙げられる。The present invention will be described in more detail. Examples of the lower alkyl group represented by R 1 and R 2 in the general formulas (1) and (2) include a methyl group, an ethyl group, a propyl group and a butyl group. The 2-hydroxypyridines represented by the general formula (1) (hereinafter referred to as 2-hydroxypyridines (1)), which are the starting materials of the present invention, include 2-hydroxypyridine, 2-hydroxy-4-methylpyridine, 2-hydroxy-4-propylpyridine, 2-hydroxy-6-methylpyridine, 2-hydroxy-4,6-dimethylpyridine and the like can be mentioned.
【０００７】本発明で用いられるニトロ化剤としては、
発煙硝酸単独、発煙硝酸と濃硫酸又は発煙硫酸との混酸
などが挙げられる。これらの中でも当該混酸が好まし
く、濃硫酸との混酸を選ぶと反応をより穏やかに進行さ
せることができ、また発煙硫酸との混酸を選ぶと収率は
濃硫酸使用時に比べ、１０％以上も向上する。The nitrating agent used in the present invention is
Examples include fuming nitric acid alone and mixed acids of fuming nitric acid and concentrated sulfuric acid or fuming sulfuric acid. Of these, the mixed acid is preferred, and the reaction can be proceeded more gently when a mixed acid with concentrated sulfuric acid is selected, and when a mixed acid with fuming sulfuric acid is selected, the yield is improved by 10% or more as compared with the use of concentrated sulfuric acid. To do.
【０００８】発煙硝酸は純度９５％（比重１．５０）以
上のものであれば充分であるが、より効率よく反応を遂
行するためには純度９８％（比重１．５２）以上のもの
が望ましい。発煙硝酸の使用量は２−ヒドロキシピリジ
ン類（１）に対して、等モル以上あれば充分であるが、
好ましくは２〜１０倍モルの範囲である。It is sufficient that the fuming nitric acid has a purity of 95% (specific gravity 1.50) or more, but a purity of 98% (specific gravity 1.52) or more is desirable for more efficient reaction. . It is sufficient that the fuming nitric acid is used in an equimolar amount or more with respect to the 2-hydroxypyridines (1).
It is preferably in the range of 2 to 10 times by mole.
【０００９】本発明に於て混酸に用いる濃硫酸および発
煙硫酸の使用量は、いずれも発煙硝酸に対して０．５〜
５倍重量使用するのが好ましい。濃硫酸および発煙硫酸
の使用量が、これ以上増えても反応になんら影響はない
が、後処理で中和に用いるアルカリ使用量とその中和液
量が増え、工業的には不利となる。The amounts of concentrated sulfuric acid and fuming sulfuric acid used as the mixed acid in the present invention are both 0.5 to 0.5 with respect to fuming nitric acid.
It is preferable to use 5 times the weight. Even if the amounts of concentrated sulfuric acid and fuming sulfuric acid used are further increased, the reaction is not affected at all, but the amount of alkali used for neutralization in the post-treatment and the amount of the neutralizing liquid are increased, which is industrially disadvantageous.
【００１０】また、２−ヒドロキシピリジン類（１）の
溶媒として濃硫酸を使用するのが好ましく、その使用量
は、反応器の撹拌が行なえる量で充分であるが、通常、
２−ヒドロキシピリジン類（１）の０．５〜５倍重量を
用いるのが好ましい。Further, it is preferable to use concentrated sulfuric acid as a solvent for the 2-hydroxypyridines (1). The amount of the concentrated sulfuric acid is sufficient so long as the reactor can be stirred.
It is preferable to use 0.5 to 5 times the weight of 2-hydroxypyridines (1).
【００１１】本反応に於いて、反応温度は６０℃以上で
あれば、特に限定されないが８０〜１５０℃が好適であ
る。反応温度が６０℃より低過ぎると反応速度が遅くな
るため反応に長時間を要し、また、２−ヒドロキシピリ
ジンの硝酸エステルと混酸が蓄積しやすくなることから
暴走反応が起こり、好ましい結果が得られない。所定の
反応温度のコントロールは、好ましくは、内温が６０℃
以上に維持され且つ濃硫酸に溶かした２−ヒドロキシピ
リジン類（１）へのニトロ化剤の供給速度を調節すれば
容易にできる。In this reaction, the reaction temperature is not particularly limited as long as it is 60 ° C. or higher, but 80 to 150 ° C. is preferable. If the reaction temperature is lower than 60 ° C., the reaction rate becomes slow, so that the reaction takes a long time, and the nitrate ester of 2-hydroxypyridine and the mixed acid are likely to accumulate, so that a runaway reaction occurs and favorable results are obtained. I can't. To control the predetermined reaction temperature, the internal temperature is preferably 60 ° C.
This can be easily done by adjusting the supply rate of the nitrating agent to the 2-hydroxypyridines (1) which is maintained above and dissolved in concentrated sulfuric acid.
【００１２】本発明の反応時間は通常２〜１０時間であ
るが、反応温度をコントロールできる範囲であれば、こ
れに限定されるものではない。The reaction time of the present invention is usually 2 to 10 hours, but is not limited to this as long as the reaction temperature can be controlled.
【００１３】このようにして得られた一般式（２）で示
される２−ヒドロキシ−３，５−ジヒドロキシピリジン
類は、一般的な中和、晶出、濾過、乾燥等の簡単な操作
で得られる。かかる操作で単離された一般式（２）で示
される２−ヒドロキシ−３，５−ジニトロピリジン類
は、通常、種々の反応の原料として用いるのに充分な純
度をもつが、必要なら適当な有機溶媒で再結晶し、純度
を上げることができる。再結晶溶媒にはメタノールなど
のアルコール類、ジメチルホルムアミド等の極性溶媒、
酢酸等の有機酸、さらにこれらの有機溶媒を組合せた混
合溶媒が選ばれる。The 2-hydroxy-3,5-dihydroxypyridines represented by the general formula (2) thus obtained can be obtained by simple operations such as general neutralization, crystallization, filtration and drying. To be The 2-hydroxy-3,5-dinitropyridines represented by the general formula (2) isolated by such an operation usually have a sufficient purity to be used as a raw material for various reactions, but are suitable if necessary. It can be recrystallized with an organic solvent to improve the purity. Alcohols such as methanol, polar solvents such as dimethylformamide,
An organic acid such as acetic acid and a mixed solvent obtained by combining these organic solvents are selected.
【００１４】[0014]
【実施例】以下に、実施例を掲げて本発明を具体的に説
明するが、本発明はこれら実施例に限定されるものでは
ない。EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
【００１５】実施例１ 撹拌器、還流冷却器、温度計の備った１リットルの４口
反応フラスコに、室温で７５ｇの濃硫酸を仕込み、撹拌
下に２５ｇの２−ヒドロキシピリジンを内温４０℃以下
に保ちながら添加した。次に、内温を８０〜９０℃に維
持しながら、１３０ｇの発煙硝酸（比重１．５２）と２
６０ｇの濃硫酸との混酸を約２時間で滴下した。この
間、酸化窒素ガスが発生したが、還流冷却器の先端から
抜き、カセイソーダ水溶液に吸収させた。混酸の滴下が
終わってから、８５℃で３時間撹拌し、冷却した。反応
液は氷５００ｇに流し込み、撹拌しながら４０％カセイ
ソーダ水溶液約８００ｇで中和（ｐＨ＝６）して結晶を
析出した。結晶を濾過し、その結晶を１リットルのビー
カーに移し、水６００ｇを加え、７０℃に昇温、撹拌し
た。２５℃に冷却し、濾過し、結晶を冷水１００ｇで洗
浄した。乾燥して、２−ヒドロキシ−３，５−ジニトロ
ピリジン３１ｇを得た。２−ヒドロキシピリジンからの
収率は６３．７％であった。Example 1 A 1-liter four-neck reaction flask equipped with a stirrer, a reflux condenser, and a thermometer was charged with 75 g of concentrated sulfuric acid at room temperature, and 25 g of 2-hydroxypyridine was stirred at an internal temperature of 40. It was added while keeping the temperature below ℃. Next, while maintaining the internal temperature at 80 to 90 ° C, 130 g of fuming nitric acid (specific gravity 1.52) and 2
60 g of mixed acid with concentrated sulfuric acid was added dropwise in about 2 hours. Nitrogen oxide gas was generated during this period, but it was extracted from the tip of the reflux condenser and absorbed in the caustic soda aqueous solution. After the dropping of the mixed acid was completed, the mixture was stirred at 85 ° C. for 3 hours and cooled. The reaction solution was poured into 500 g of ice and neutralized (pH = 6) with about 800 g of 40% caustic soda aqueous solution with stirring to precipitate crystals. The crystals were filtered, transferred to a 1-liter beaker, 600 g of water was added, and the mixture was heated to 70 ° C. and stirred. It was cooled to 25 ° C., filtered and the crystals washed with 100 g cold water. After drying, 31 g of 2-hydroxy-3,5-dinitropyridine was obtained. The yield based on 2-hydroxypyridine was 63.7%.
【００１６】実施例２ ２−ヒドロキシ−４−メチルピリジン２９ｇを用いた以
外は実施例１と同様に操作を行なった結果、２−ヒドロ
キシ−３，５−ジニトロ−４−メチルピリジンの収率は
５５％であった。Example 2 The procedure of Example 1 was repeated except that 29 g of 2-hydroxy-4-methylpyridine was used. As a result, the yield of 2-hydroxy-3,5-dinitro-4-methylpyridine was found to be It was 55%.
【００１７】実施例３ ２−ヒドロキシ−６−メチルピリジン２９ｇを用いた以
外は実施例１と同様に操作を行なった結果、２−ヒドロ
キシ−６−メチル−３，５−ジニトロピリジンの収率は
５７％であった。Example 3 The same operation as in Example 1 was carried out except that 29 g of 2-hydroxy-6-methylpyridine was used, and as a result, the yield of 2-hydroxy-6-methyl-3,5-dinitropyridine was found to be It was 57%.
【００１８】実施例４ 混酸に用いた濃硫酸の代りに、２０％発煙硫酸を用いた
他は、実施例１と同様に行った結果、２−ヒドロキシピ
リジンに対する２−ヒドロキシ−３，５−ジニトロピリ
ジンの収率は８１．３％であった。なお、混酸の滴下速
度を調節することによって発泡及び発熱を容易にコント
ロールでき安全に反応を行うことができた。Example 4 The same procedure as in Example 1 was carried out except that 20% fuming sulfuric acid was used in place of the concentrated sulfuric acid used as the mixed acid. As a result, 2-hydroxy-3,5-dinitro with respect to 2-hydroxypyridine was obtained. The yield of pyridine was 81.3%. By controlling the dropping rate of the mixed acid, foaming and heat generation could be easily controlled and the reaction could be safely performed.
【００１９】比較例 濃硫酸の代りに２０％の発煙硫酸用い、２０℃で反応し
た後、８５℃まで昇温した他は、実施例１と同様に行っ
た所、２−ヒドロキシピリジンに対する２−ヒドロキシ
−３，５−ジニトロピリジンの収率は５３％であった。
なお、２０℃から８５℃に昇温する時に、夥しい発泡を
伴って、急激な発熱があった。Comparative Example The same procedure as in Example 1 was repeated except that 20% fuming sulfuric acid was used instead of concentrated sulfuric acid, the reaction was carried out at 20 ° C., and then the temperature was raised to 85 ° C. The yield of hydroxy-3,5-dinitropyridine was 53%.
In addition, when the temperature was raised from 20 ° C. to 85 ° C., a sudden heat generation was accompanied by a large amount of foaming.
【００２０】[0020]
【発明の効果】本発明の方法によれば、従来技術に比較
して、安全にジニトロ化反応を行うことができ、かつ高
い収率で目的物の２−ヒドロキシ−３，５−ジニトロピ
リジン類を製造でき、本発明は工業的に極めて有用なも
のである。INDUSTRIAL APPLICABILITY According to the method of the present invention, 2-hydroxy-3,5-dinitropyridines, which are the target compounds, can be safely subjected to the dinitration reaction and have a high yield as compared with the prior art. The present invention is industrially extremely useful.
Claims (3)
ル基を意味する）で表される２−ヒドロキシピリジン類
をジニトロ化して一般式（２）： 【化２】 （式中、Ｒ1およびＲ2は前記に同じ）で表される２−ヒ
ドロキシ−３，５−ジニトロピリジン類を製造するにあ
たり、２−ヒドロキシピリジン類にニトロ化剤を供給し
ながら、反応温度６０℃以上でジニトロ化することを特
徴とする２−ヒドロキシ−３，５−ジニトロピリジン類
の製造法。1. General formula (1): (Wherein R 1 and R 2 each represent a hydrogen atom or a lower alkyl group) is dinitrated to give a compound of general formula (2): (In the formula, R 1 and R 2 are the same as above) In producing 2-hydroxy-3,5-dinitropyridines, a reaction temperature is supplied to the 2-hydroxypyridines while supplying a nitrating agent. A process for producing 2-hydroxy-3,5-dinitropyridines, which comprises dinitration at 60 ° C. or higher.
又は発煙硝酸と発煙硫酸の混合物である請求項１記載の
製造法2. The method according to claim 1, wherein the nitrating agent is a mixture of fuming nitric acid and concentrated sulfuric acid or a mixture of fuming nitric acid and fuming sulfuric acid.
項１または２記載の製造法。3. The method according to claim 1, wherein the reaction temperature is 80 ° C. to 150 ° C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03263193A JP3261190B2 (en) | 1993-01-27 | 1993-01-27 | Method for producing 2-hydroxy-3,5-dinitropyridines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03263193A JP3261190B2 (en) | 1993-01-27 | 1993-01-27 | Method for producing 2-hydroxy-3,5-dinitropyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06220019A true JPH06220019A (en) | 1994-08-09 |
| JP3261190B2 JP3261190B2 (en) | 2002-02-25 |
Family
ID=12364206
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03263193A Expired - Fee Related JP3261190B2 (en) | 1993-01-27 | 1993-01-27 | Method for producing 2-hydroxy-3,5-dinitropyridines |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3261190B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997024327A1 (en) * | 1996-01-02 | 1997-07-10 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Process for preparing 2,4-dihydroxypyridine and 2,4-dihydroxy-3-nitropyridine |
| JPWO2007091392A1 (en) * | 2006-02-10 | 2009-07-02 | 三井化学株式会社 | Method for producing O-methyl-N-nitroisourea |
| CN114751855A (en) * | 2022-05-23 | 2022-07-15 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
-
1993
- 1993-01-27 JP JP03263193A patent/JP3261190B2/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997024327A1 (en) * | 1996-01-02 | 1997-07-10 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Process for preparing 2,4-dihydroxypyridine and 2,4-dihydroxy-3-nitropyridine |
| US6307054B1 (en) | 1996-01-02 | 2001-10-23 | Aventis Pharmaceuticals Products Inc. | Process for preparing 2,4- dihydroxypyridine and 2,4- dihydroxy-3-nitropyridine |
| US6392049B1 (en) | 1996-01-02 | 2002-05-21 | Aventis Pharmaceuticals Inc. | Process for preparing 2,4-dihydroxypyridine and 2,4-dihydroxy-3-nitropyridine |
| JPWO2007091392A1 (en) * | 2006-02-10 | 2009-07-02 | 三井化学株式会社 | Method for producing O-methyl-N-nitroisourea |
| JP4516609B2 (en) * | 2006-02-10 | 2010-08-04 | 三井化学アグロ株式会社 | Method for producing O-methyl-N-nitroisourea |
| US7786325B2 (en) | 2006-02-10 | 2010-08-31 | Mitsui Chemicals, Inc. | Process for producing O-methyl-N-nitroisourea |
| CN114751855A (en) * | 2022-05-23 | 2022-07-15 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
| CN114751855B (en) * | 2022-05-23 | 2024-05-07 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3261190B2 (en) | 2002-02-25 |
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