JPH05339236A - Production of 2,3-diaminopyridines - Google Patents
Production of 2,3-diaminopyridinesInfo
- Publication number
- JPH05339236A JPH05339236A JP4171664A JP17166492A JPH05339236A JP H05339236 A JPH05339236 A JP H05339236A JP 4171664 A JP4171664 A JP 4171664A JP 17166492 A JP17166492 A JP 17166492A JP H05339236 A JPH05339236 A JP H05339236A
- Authority
- JP
- Japan
- Prior art keywords
- diaminopyridines
- acid
- amino
- nitro
- alcohol
- 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
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical class NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 8
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- KFVGEPWMVKZPND-UHFFFAOYSA-N 5-bromo-4-methyl-3-nitropyridin-2-amine Chemical compound CC1=C(Br)C=NC(N)=C1[N+]([O-])=O KFVGEPWMVKZPND-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QOOCOFOGYRQPPN-UHFFFAOYSA-N 5-bromo-3-nitropyridin-2-amine Chemical compound NC1=NC=C(Br)C=C1[N+]([O-])=O QOOCOFOGYRQPPN-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YRGMYJUKFJPNPD-UHFFFAOYSA-N 5-bromopyridine-2,3-diamine Chemical compound NC1=CC(Br)=CN=C1N YRGMYJUKFJPNPD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- OVYTZAASVAZITK-UHFFFAOYSA-M sodium;ethanol;hydroxide Chemical compound [OH-].[Na+].CCO OVYTZAASVAZITK-UHFFFAOYSA-M 0.000 description 2
- 229910052712 strontium Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- -1 2,3-diaminopyridine dihydrobromide Chemical compound 0.000 description 1
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 1
- GZBKVUGZEAJYHH-UHFFFAOYSA-N 2-nitropyridin-3-amine Chemical compound NC1=CC=CN=C1[N+]([O-])=O GZBKVUGZEAJYHH-UHFFFAOYSA-N 0.000 description 1
- BPYHGTCRXDWOIQ-UHFFFAOYSA-N 3-nitropyridin-2-amine Chemical compound NC1=NC=CC=C1[N+]([O-])=O BPYHGTCRXDWOIQ-UHFFFAOYSA-N 0.000 description 1
- VGENLLAEDBMNSC-UHFFFAOYSA-N 4-methyl-2-nitropyridine Chemical compound CC1=CC=NC([N+]([O-])=O)=C1 VGENLLAEDBMNSC-UHFFFAOYSA-N 0.000 description 1
- RWGGFJXJRPCCGD-UHFFFAOYSA-N 4-methylpyridine-2,3-diamine Chemical compound CC1=CC=NC(N)=C1N RWGGFJXJRPCCGD-UHFFFAOYSA-N 0.000 description 1
- JUHYRNRJCOGLEB-UHFFFAOYSA-N 4-methylpyridine-2,3-diamine dihydrobromide Chemical compound Br.Br.Cc1ccnc(N)c1N JUHYRNRJCOGLEB-UHFFFAOYSA-N 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-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
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 238000005695 dehalogenation reaction Methods 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、アンギオテンシンII拮
抗剤の合成をはじめとして縮合イミダゾール系化合物の
合成に有用である２，３−ジアミノピリジン類の製造方
法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 2,3-diaminopyridines which is useful for the synthesis of condensed imidazole compounds, including the synthesis of angiotensin II antagonists.
【０００２】[0002]
【従来の技術】従来、２，３−ジアミノ−４−アルキル
ピリジンの如き２，３−ジアミノピリジン類の製造方法
としては２，３−ジアミノ−５−ブロモピリジンを水
酸化ナトリウム水溶液中、パラジウム−ストロンチウム
存在下で脱ブロム化して２，３−ジアミノピリジンを生
成させたのちエーテルで抽出し、抽出液を濃縮、乾固
し、次いでベンゼンにより再結晶を行い、目的物を単離
する方法（Ｏｒｇ．Ｓｙｎ．Ｃｏｌｌ．Ｖｏｌ５，Ｐ３
４６）；２−アミノ−３−ニトロピリジンと塩酸をア
ルコール溶液中、鉄の存在下で反応させ、２，３−ジア
ミノピリジンを製造した後ベンゼンで抽出を行い単離す
る方法（Ｊ．Ｃ．Ｓ．，Ｐ１３８９〜１３９１（１９４
８））；２−アミノ−３−ニトロ−５−ブロモピリジ
ンを水酸化ナトリウム−エタノール溶液中、ラーニーニ
ッケルの存在下で２，３−ジアミノピリジンを製造した
後エーテルで抽出し、抽出物をベンゼンにより再結晶し
て単離する方法又は２，３−ジアミノ−５−ブロモピリ
ジンを水素ガス中において水酸化ナトリウム溶液中、パ
ラジウム−ストロンチウム存在下で反応させ２，３−ジ
アミノピリジンを製造した後エーテルで抽出し、抽出物
をベンゼンにより再結晶して単離する方法（Ｊ．Ｃ．
Ｓ．，Ｐ４０３９〜４０４０（１９５４））；２−ニ
トロ−３−アミノピリジンを水素ガス中においてメタノ
ール溶液中、ラーニーニッケルの存在下で反応させ２，
３−ジアミノピリジンを製造した後、ベンゼンにより再
結晶を行い単離する方法（Ｊ．Ｃ．Ｓ．，Ｐ４４２〜４
４６（１９５７））；２−アミノ−３−ニトロ−５−
クロルピリジンを水酸化ナトリウム−エタノール溶液
中、ラーニーニッケルの存在下で反応させ２，３−ジア
ミノピリジンを製造した後エタノールで抽出し、抽出物
を石油ベンゼンにより再結晶して単離する方法（ＪＡＣ
Ｓ．，７１（１９４９）１８９１）；２−アミノ−３−
ニトロ−４−メチルピリジンをエタノール溶液中、パラ
ジウム−カーボンの存在下で反応させ２，３−ジアミノ
−４−メチルピリジンを製造した後ベンゼン−ヘキサン
溶液により再結晶を行い単離する方法（ＪＡＣＳ．，７
２（１９５０）２８０６）等種々の方法が挙げられる。2. Description of the Related Art Conventionally, as a method for producing 2,3-diaminopyridines such as 2,3-diamino-4-alkylpyridine, 2,3-diamino-5-bromopyridine is treated with palladium hydroxide in an aqueous sodium hydroxide solution. A method of isolating the desired product by debrominating in the presence of strontium to form 2,3-diaminopyridine, extracting with ether, concentrating the extract to dryness, and then recrystallizing with benzene to isolate the desired product (Org .Syn.Col.Vol5, P3
46); A method of reacting 2-amino-3-nitropyridine and hydrochloric acid in an alcohol solution in the presence of iron to produce 2,3-diaminopyridine, followed by extraction with benzene for isolation (J.C. S., P 1389-1391 (194
8)); 2-Amino-3-nitro-5-bromopyridine was prepared in a sodium hydroxide-ethanol solution in the presence of Lani nickel to prepare 2,3-diaminopyridine and then extracted with ether, and the extract was extracted with benzene. Or by recrystallizing and isolating 2,3-diamino-5-bromopyridine in hydrogen gas in a sodium hydroxide solution in the presence of palladium-strontium to produce 2,3-diaminopyridine, and then ether. And then recrystallize the extract with benzene to isolate (J.C.
S. , P4039-4040 (1954)); 2-nitro-3-aminopyridine is reacted in hydrogen gas in a methanol solution in the presence of Lani nickel.
A method of producing 3-diaminopyridine and then recrystallizing it with benzene to isolate it (JCS, P442-4).
46 (1957)); 2-amino-3-nitro-5-.
A method in which chloropyridine is reacted in a sodium hydroxide-ethanol solution in the presence of Lerney nickel to produce 2,3-diaminopyridine, which is then extracted with ethanol, and the extract is recrystallized from petroleum benzene and isolated (JAC
S. , 71 (1949) 1891); 2-amino-3-.
A method in which nitro-4-methylpyridine is reacted in an ethanol solution in the presence of palladium-carbon to produce 2,3-diamino-4-methylpyridine, which is then recrystallized from a benzene-hexane solution for isolation (JACS. , 7
2 (1950) 2806).
【０００３】[0003]
【発明が解決すべき課題】しかしながら、かかる方法に
おいてはベンゼン、エーテル等毒性の強い有機溶媒を使
用せざるを得ない上、２，３−ジアミノピリジンが水と
有機溶媒との双方に可溶であるため抽出を行うには非常
に大量の有機溶媒が必要であり、更に操作を繰り返し行
なわなければならなかったり又非常に長時間の抽出操作
を実施しなければならない等の欠点を有しており、いず
れの公知技術においても経済性、作業性及び安全性等が
悪く、工業的規模での実施においては満足できるもので
はない。従ってかかる効率の悪い溶媒抽出を行わず単離
操作が容易である２，３−ジアミノピリジン類の新規な
製造方法が強く望まれている。However, in such a method, a highly toxic organic solvent such as benzene and ether must be used, and 2,3-diaminopyridine is soluble in both water and the organic solvent. For this reason, it requires a very large amount of organic solvent to perform extraction, and has the drawback that it requires repeated operations and that it requires an extremely long extraction operation. However, all of the known techniques are poor in economical efficiency, workability, safety, etc., and are not satisfactory in practice on an industrial scale. Therefore, there is a strong demand for a novel method for producing 2,3-diaminopyridines which is easy to isolate without performing such inefficient solvent extraction.
【０００４】[0004]
【課題を解決するための手段】しかるに本発明者等はか
かる課題を解決すべく鋭意研究を重ねた結果、アルコー
ル又は水溶媒中で２−アミノ−３−ニトロ−５−ハロピ
リジン類をパラジウム触媒の存在下水素ガス中で脱ハロ
ゲン化及び還元を行って、２，３−ジアミノピリジン類
を製造し、ついでかかる系に塩酸、硫酸又は臭化水素酸
から選ばれる無機酸の少なくとも１種を添加して、２，
３−ジアミノピリジン類の酸付加塩として単離する場
合、かかる目的に合致することを見出し本発明を完成す
るに至った。以下、本発明について詳述する。However, as a result of intensive studies by the present inventors in order to solve such problems, the inventors have found that 2-amino-3-nitro-5-halopyridines can be treated with palladium catalysts in alcohol or water solvent. Dehalogenation and reduction are carried out in the presence of hydrogen gas to produce 2,3-diaminopyridines, and then at least one inorganic acid selected from hydrochloric acid, sulfuric acid or hydrobromic acid is added to the system. 2
In the case of isolation as an acid addition salt of 3-diaminopyridines, it was found that this purpose is met, and the present invention has been completed. Hereinafter, the present invention will be described in detail.
【０００５】本発明においては上記の如くアルコール又
は水溶媒中で２−アミノ−３−ニトロ−５−ハロピリジ
ン類をパラジウム触媒の存在下水素ガス中で脱ハロゲン
化及び還元を行うことにより２，３−ジアミノピリジン
類を製造する。本発明における２−アミノ−３−ニトロ
−５−ハロピリジン類とは化１で表される。式中Ｒは水
素原子又はアルキル基を示し、Ｘは塩素原子又は臭素原
子を示す。In the present invention, as described above, by dehalogenating and reducing 2-amino-3-nitro-5-halopyridines in hydrogen gas in the presence of a palladium catalyst in an alcohol or water solvent, 2,3 -Prepare diaminopyridines. The 2-amino-3-nitro-5-halopyridines in the present invention are represented by Chemical formula 1. In the formula, R represents a hydrogen atom or an alkyl group, and X represents a chlorine atom or a bromine atom.
【０００６】[0006]
【化１】 [Chemical 1]
【０００７】溶媒としてはアルコール又は水が使用され
る。上記アルコールとは特に制限はなく、メタノール、
エタノール、プロパノール、イソプロパノール、ブタノ
ール、イソブタノール、ｓｅｃ−ブタノール、ｔｅｒｔ
−ブタノール等が挙げられる。アルコール同志又はアル
コールと水とを混合して用いても良い。但しこれらに限
定されるものではない。かかる溶媒の使用量としては２
−アミノ−３−ニトロ−５−ハロピリジン類１重量部に
対して１０〜１００重量部、好ましくは１０〜２５重量
部である。Alcohol or water is used as the solvent. The alcohol is not particularly limited, methanol,
Ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, tert
-Butanol and the like. The alcohols may be the same or the alcohol and water may be mixed and used. However, it is not limited to these. The amount of such solvent used is 2
It is 10 to 100 parts by weight, preferably 10 to 25 parts by weight, relative to 1 part by weight of -amino-3-nitro-5-halopyridines.
【０００８】本発明における触媒としてはパラジウム触
媒が用いられ、通常はカーボンやアルミナ、シリカ等の
担体に０．５〜２０重量％程度の量が担持されて用いら
れる。かかるパラジウム触媒の使用量は純分換算で２−
アミノ−３−ニトロ−５−ハロピリジン類１重量部に対
して０．００２５〜０．０２５重量部、好ましくは０．
０１〜０．０１５重量部が適当である。本発明における
反応は水素ガス中で行われ、その水素圧は２〜１５ｋｇ
／ｃｍ2、好ましくは４〜５ｋｇ／ｃｍ2である。反応温
度は１５〜８０℃、好ましくは３５〜６０℃が適当であ
り、通常０．５〜１時間程度で反応は終了する。A palladium catalyst is used as the catalyst in the present invention, and it is usually used by supporting it on a carrier such as carbon, alumina or silica in an amount of about 0.5 to 20% by weight. The amount of the palladium catalyst used is calculated as 2-
Amino-3-nitro-5-halopyridines are added in an amount of 0.0025 to 0.025 part by weight, preferably 0.1.
01 to 0.015 parts by weight is suitable. The reaction in the present invention is carried out in hydrogen gas, and the hydrogen pressure is 2 to 15 kg.
/ Cm 2 , preferably 4 to 5 kg / cm 2 . The reaction temperature is suitably 15 to 80 ° C, preferably 35 to 60 ° C, and the reaction is usually completed in about 0.5 to 1 hour.
【０００９】上記の如く得られた２，３−ジアミノピリ
ジン類は次に単離工程に付される。単離を行うにあたっ
ては反応液中からパラジウム触媒を濾別した後、塩酸、
硫酸又は臭化水素酸から選ばれる無機酸の少なくとも１
種を添加して、２，３−ジアミノピリジン類の酸付加塩
を生成させる。かかる酸は通常５〜９８％程度の水溶液
として用いられ、その使用量は２−アミノ−３−ニトロ
−５−ハロピリジンに対して１〜３倍モル、好ましくは
２〜２．５倍モルが適当である。The 2,3-diaminopyridines obtained as described above are then subjected to an isolation step. For isolation, the palladium catalyst is filtered off from the reaction solution, then hydrochloric acid,
At least one of inorganic acids selected from sulfuric acid or hydrobromic acid
Seeds are added to form acid addition salts of 2,3-diaminopyridines. Such an acid is usually used as an aqueous solution of about 5 to 98%, and the amount thereof used is 1 to 3 times mol, preferably 2 to 2.5 times mol, of 2-amino-3-nitro-5-halopyridine. Is.
【００１０】上記の酸付加塩の生成液はついで、必要に
応じて部分濃縮等を行い、結晶の析出を完全なものとす
る。かかる生成液はそのまま濾過してもよいが、操作性
を向上させるため２，３−ジアミノピリジン類の酸付加
塩を溶解しない酢酸メチル、酢酸エチル、酢酸ブチル、
アセトン、メチルエチルケトン、ジクロロエタン、クロ
ロホルム等を適量添加して溶液粘度を下げた後濾過操作
を行い目的物である２，３−ジアミノピリジン酸付加塩
を濾別する。かかる２，３−ジアミノピリジン類の酸付
加塩は必要に応じて更に洗浄等任意の方法により精製が
行われる。かくして得られた２，３−ジアミノピリジン
類の酸付加塩はそのままあるいは付加した酸を周知の方
法で離脱させた後、各種の有機合成用の原料として用い
られる。The acid addition salt product solution is then subjected to partial concentration, if necessary, to complete the precipitation of crystals. Such a product solution may be filtered as it is, but in order to improve operability, methyl acetate, ethyl acetate, butyl acetate, which does not dissolve the acid addition salt of 2,3-diaminopyridine,
Acetone, methyl ethyl ketone, dichloroethane, chloroform and the like are added in an appropriate amount to reduce the solution viscosity, and a filtration operation is performed to separate the target 2,3-diaminopyridine acid addition salt by filtration. The acid addition salt of 2,3-diaminopyridines may be further purified by any method such as washing, if necessary. The acid addition salt of 2,3-diaminopyridine thus obtained is used as a raw material for various organic syntheses as it is or after the added acid is removed by a known method.
【００１１】[0011]
【作用】本発明は取り扱いが容易なアルコール又は水溶
媒を用い、２，３−ジアミノピリジン類を酸付加塩とし
て晶析法にて単離を行うことにより従来法に比べて単離
操作が非常に簡略化でき、工業的にみて極めて有利であ
る。The present invention uses an alcohol or water solvent that is easy to handle and isolates 2,3-diaminopyridines as an acid addition salt by the crystallization method. It can be simplified and is industrially extremely advantageous.
【００１２】[0012]
【実施例】以下、本発明について実例を挙げ更に詳述す
る。 実施例１ ２−アミノ−５−ブロモ−３−ニトロ−４−メチルピリ
ジン１２．９４ｇ（５５．８ミリモル）、含水率５０重
量％のパラジウムカーボン（パラジウム担持量５重量
％）８．３５ｇ、メタノール６００ｍｌを反応器に仕込
み、水素圧４．０ｋｇ／ｃｍ２下で２３．５〜４９．５
℃で５０分反応させた。反応終了後パラジウムカーボン
を濾別した後、濾液に４７％臭化水素酸水２０．６６ｇ
（１２０ミリモル）を加え、部分濃縮を行い、スラリー
液を得た。これに酢酸エチル５０ｍｌを加えた後濾過を
行い、乾燥して１３．５６ｇの結晶を得た。かかる結晶
は1Ｈ−ＮＭＲにより分析したところ２，３−ジアミノ
−４−メチルピリジン・２臭化水素酸塩であった。２−
アミノ−５−ブロモ−３−ニトロ−４−メチルピリジン
に対する収率は７８．０％であった。The present invention will be described in more detail below with reference to actual examples. Example 1 12.94 g (55.8 mmol) of 2-amino-5-bromo-3-nitro-4-methylpyridine, 8.35 g of palladium carbon having a water content of 50% by weight (palladium supported amount: 5% by weight), methanol 600 ml was charged into a reactor, and 23.5-49.5 under hydrogen pressure of 4.0 kg / cm 2.
The reaction was carried out at 50 ° C for 50 minutes. After the reaction was completed, palladium carbon was filtered off, and then the filtrate was mixed with 47% hydrobromic acid water (20.66 g).
(120 mmol) was added and partial concentration was performed to obtain a slurry liquid. 50 ml of ethyl acetate was added to this, followed by filtration and drying to obtain 13.56 g of crystals. When the crystals were analyzed by 1 H-NMR, they were 2,3-diamino-4-methylpyridine dihydrobromide. 2-
The yield based on amino-5-bromo-3-nitro-4-methylpyridine was 78.0%.
【００１３】実施例２ ２−アミノ−５−ブロモ−３−ニトロピリジン３．２７
ｇ（１５ミリモル）、実施例１と同様のパラジウムカー
ボン１．９６ｇ、メタノール１００ｍｌを反応器に仕込
み、水素圧４．０ｋｇ／ｃｍ２下で２３．５〜４９．５
℃で５０分反応させた。反応終了後パラジウムカーボン
を濾別した後、濾液に４７％臭化水素酸水５．１７ｇ
（３０ミリモル）を加え、部分濃縮を行い、スラリー液
とした。これに酢酸エチル２０ｍｌを加えた後濾過を行
い、乾燥して３．０８ｇの結晶を得た。かかる結晶は1
Ｈ−ＮＭＲにより分析したところ２，３−ジアミノピリ
ジン・２臭化水素酸塩であった。２−アミノ−５−ブロ
モ−３−ニトロピリジンに対する収率は７５．０％であ
った。Example 2 2-amino-5-bromo-3-nitropyridine 3.27
g (15 mmol), 1.96 g of the same palladium carbon as in Example 1, and 100 ml of methanol were charged into a reactor, and 23.5 to 49.5 under a hydrogen pressure of 4.0 kg / cm 2.
The reaction was carried out at 50 ° C for 50 minutes. After the reaction was completed, palladium carbon was filtered off, and the filtrate was then mixed with 47% aqueous hydrobromic acid (5.17 g).
(30 mmol) was added and partial concentration was performed to obtain a slurry liquid. After 20 ml of ethyl acetate was added to this, filtration was performed and drying was performed to obtain 3.08 g of crystals. 1 such crystal
It was 2,3-diaminopyridine dihydrobromide as analyzed by 1 H-NMR. The yield based on 2-amino-5-bromo-3-nitropyridine was 75.0%.
【００１４】実施例３ 実施例１において、４７％臭化水素酸水２０．６６ｇに
代えて３５％塩酸１２．５１ｇ（１２０ミリモル）とし
た以外は同例に従って実験を行ったところ１３．０５ｇ
の結晶が得られた。1Ｈ−ＮＭＲで分析したところ２，
３−ジアミノ−４−メチルピリジン・２塩酸塩であっ
た。２−アミノ−５−ブロモ−３−ニトロ−４−メチル
ピリジンに対する収率は７６．０％であった。Example 3 An experiment was conducted according to the same example as in Example 1 except that 20.66 g of 47% hydrobromic acid water was replaced by 12.51 g (120 mmol) of 35% hydrochloric acid, and 13.05 g was obtained.
The crystals of When analyzed by 1 H-NMR, 2,
It was 3-diamino-4-methylpyridine dihydrochloride. The yield based on 2-amino-5-bromo-3-nitro-4-methylpyridine was 76.0%.
【００１５】実施例４ 実施例１において、４７％臭化水素酸水２０．６６ｇに
代えて６８％硫酸１７．３０ｇ（１２０ミリモル）とし
た以外は同例に従って実験を行ったところ９．８８ｇの
結晶が得られた。1Ｈ−ＮＭＲで分析したところ２，３
−ジアミノ−４−メチルピリジン・２塩酸塩であった。
２−アミノ−５−ブロモ−３−ニトロ−４−メチルピリ
ジンに対する収率は７２．０％であった。Example 4 An experiment was conducted according to the same example as in Example 1 except that 20.66 g of 47% hydrobromic acid water was replaced with 17.30 g (120 mmol) of 68% sulfuric acid. Crystals were obtained. When analyzed by 1 H-NMR, a few
It was -diamino-4-methylpyridine dihydrochloride.
The yield based on 2-amino-5-bromo-3-nitro-4-methylpyridine was 72.0%.
【００１６】[0016]
【発明の効果】本発明は取り扱い容易な汎用溶媒を用い
かつ、単離操作が極めて容易である新規な方法により
２，３−ジアミノ−４−アルキルピリジン類を製造する
ことができる。INDUSTRIAL APPLICABILITY According to the present invention, 2,3-diamino-4-alkylpyridines can be produced by a novel method using a general-purpose solvent that is easy to handle and a very easy isolation operation.
Claims (1)
３−ニトロ−５−ハロピリジン類をパラジウム触媒の存
在下水素ガス中で脱ハロゲン化及び還元を行って２，３
−ジアミノピリジン類を製造し、ついでかかる系に塩
酸、硫酸又は臭化水素酸から選ばれる無機酸の少なくと
も１種を添加して、２，３−ジアミノピリジン類の酸付
加塩として単離することを特徴とする２，３−ジアミノ
ピリジン類の製造方法1. 2-Amino-in alcohol or water solvent
2-Nitro-5-halopyridines were dehalogenated and reduced in hydrogen gas in the presence of a palladium catalyst to give 2,3
-Producing diaminopyridines and then adding at least one inorganic acid selected from hydrochloric acid, sulfuric acid or hydrobromic acid to the system, and isolating as an acid addition salt of 2,3-diaminopyridines. And a method for producing 2,3-diaminopyridines
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04171664A JP3088561B2 (en) | 1992-06-05 | 1992-06-05 | Method for producing 2,3-diaminopyridines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04171664A JP3088561B2 (en) | 1992-06-05 | 1992-06-05 | Method for producing 2,3-diaminopyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05339236A true JPH05339236A (en) | 1993-12-21 |
| JP3088561B2 JP3088561B2 (en) | 2000-09-18 |
Family
ID=15927415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04171664A Expired - Fee Related JP3088561B2 (en) | 1992-06-05 | 1992-06-05 | Method for producing 2,3-diaminopyridines |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3088561B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003012647A (en) * | 2000-10-04 | 2003-01-15 | Shionogi & Co Ltd | Method for producing 2,3-diaminopyridine |
| WO2004069802A1 (en) * | 2003-02-06 | 2004-08-19 | Shionogi & Co., Ltd. | Process for producing 2-amino-3-substituted pyridine |
| DE102009022830A1 (en) | 2008-10-24 | 2010-04-29 | Jubilant Organosys Ltd. | Preparing 2,3-diaminopyridine compounds, useful e.g. as intermediates to produce pharmaceutical compounds, comprises aminating 3-amino-2-halopyridine compounds with aqueous ammonia in the presence of catalyst, heating and extracting |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0751398A (en) * | 1993-08-12 | 1995-02-28 | Nissho Sangyo Kk | Injection head for carbon dioxide fire extinguisher |
-
1992
- 1992-06-05 JP JP04171664A patent/JP3088561B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003012647A (en) * | 2000-10-04 | 2003-01-15 | Shionogi & Co Ltd | Method for producing 2,3-diaminopyridine |
| WO2004069802A1 (en) * | 2003-02-06 | 2004-08-19 | Shionogi & Co., Ltd. | Process for producing 2-amino-3-substituted pyridine |
| JPWO2004069802A1 (en) * | 2003-02-06 | 2006-05-25 | 塩野義製薬株式会社 | Method for producing 2-amino-3-substituted pyridine |
| DE102009022830A1 (en) | 2008-10-24 | 2010-04-29 | Jubilant Organosys Ltd. | Preparing 2,3-diaminopyridine compounds, useful e.g. as intermediates to produce pharmaceutical compounds, comprises aminating 3-amino-2-halopyridine compounds with aqueous ammonia in the presence of catalyst, heating and extracting |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3088561B2 (en) | 2000-09-18 |
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