JPH0597815A - Method for synthesizing 4(5)-thiocarbamoyl-imidazole compound - Google Patents
Method for synthesizing 4(5)-thiocarbamoyl-imidazole compoundInfo
- Publication number
- JPH0597815A JPH0597815A JP3335794A JP33579491A JPH0597815A JP H0597815 A JPH0597815 A JP H0597815A JP 3335794 A JP3335794 A JP 3335794A JP 33579491 A JP33579491 A JP 33579491A JP H0597815 A JPH0597815 A JP H0597815A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- aqueous solution
- mol
- thiocarbamoyl
- ammonium sulfide
- 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
- 238000000034 method Methods 0.000 title claims description 9
- 230000002194 synthesizing effect Effects 0.000 title claims description 3
- -1 imidazoledithiocarboxylic acid compound Chemical class 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 3
- 229910052788 barium Inorganic materials 0.000 claims abstract 2
- 229910052791 calcium Inorganic materials 0.000 claims abstract 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 2
- 229910052700 potassium Inorganic materials 0.000 claims abstract 2
- 229910052708 sodium Inorganic materials 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims 1
- 239000011575 calcium Chemical group 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 239000011591 potassium Chemical group 0.000 claims 1
- 239000011734 sodium Chemical group 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 abstract description 26
- UYJXRRSPUVSSMN-UHFFFAOYSA-P ammonium sulfide Chemical compound [NH4+].[NH4+].[S-2] UYJXRRSPUVSSMN-UHFFFAOYSA-P 0.000 abstract description 21
- 238000006243 chemical reaction Methods 0.000 abstract description 11
- 229920001021 polysulfide Polymers 0.000 abstract description 10
- 239000005077 polysulfide Substances 0.000 abstract description 10
- 150000008117 polysulfides Polymers 0.000 abstract description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000010438 heat treatment Methods 0.000 abstract description 8
- 229910021529 ammonia Inorganic materials 0.000 abstract description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 12
- WREDNSAXDZCLCP-UHFFFAOYSA-N methanedithioic acid Chemical compound SC=S WREDNSAXDZCLCP-UHFFFAOYSA-N 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 239000004927 clay Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000013076 target substance Substances 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000002023 dithiocarboxylic acids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- CUOPCGNBQZKKNU-UHFFFAOYSA-N 1h-imidazole-5-carbothioamide Chemical compound NC(=S)C1=CN=CN1 CUOPCGNBQZKKNU-UHFFFAOYSA-N 0.000 description 1
- QLTXPYPAYKMBTK-UHFFFAOYSA-N 2-ethyl-1h-imidazole-5-carbodithioic acid Chemical compound CCC1=NC=C(C(S)=S)N1 QLTXPYPAYKMBTK-UHFFFAOYSA-N 0.000 description 1
- RWLPQGDQZBGTIT-UHFFFAOYSA-N 2-heptadecyl-1H-imidazole-5-carbothioamide Chemical compound CCCCCCCCCCCCCCCCCC1=NC=C(C(N)=S)N1 RWLPQGDQZBGTIT-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- IZYGCWIXHKMALW-UHFFFAOYSA-N 2-methyl-1h-imidazole-5-carbodithioic acid Chemical compound CC1=NC=C(C(S)=S)N1 IZYGCWIXHKMALW-UHFFFAOYSA-N 0.000 description 1
- BPFXGDCUBZBEQF-UHFFFAOYSA-N 2-phenyl-1h-imidazole-5-carbodithioic acid Chemical compound N1C(C(=S)S)=CN=C1C1=CC=CC=C1 BPFXGDCUBZBEQF-UHFFFAOYSA-N 0.000 description 1
- NBTYCLMJMWDTMQ-UHFFFAOYSA-N 2-phenyl-1h-imidazole-5-carbothioamide Chemical compound N1C(C(=S)N)=CN=C1C1=CC=CC=C1 NBTYCLMJMWDTMQ-UHFFFAOYSA-N 0.000 description 1
- RQFZMOFDFJECFP-UHFFFAOYSA-N 2-propan-2-yl-1H-imidazole-5-carbothioamide Chemical compound CC(C)C1=NC=C(C(N)=S)N1 RQFZMOFDFJECFP-UHFFFAOYSA-N 0.000 description 1
- MPIUYKLPIBBKAT-UHFFFAOYSA-N 2-undecyl-1H-imidazole-5-carbothioamide Chemical compound CCCCCCCCCCCC1=NC=C(C(N)=S)N1 MPIUYKLPIBBKAT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000011363 dried mixture Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明方法によって得られる化合
物は、それ自身に生物活性が期待される他に同じく生物
活性が期待できる4(5)−カルバモイル−イミダゾール化
合物、4(5)−シアノイミダゾール化合物及び4(5)−アミ
ノメチルイミダゾール化合物の前駆体となるものであ
り、従って本発明方法は医薬あるいは農薬分野において
有望なものである。INDUSTRIAL APPLICABILITY The compound obtained by the method of the present invention is a 4 (5) -carbamoyl-imidazole compound, 4 (5) -cyanoimidazole, which is expected to have biological activity in addition to itself. The compounds are precursors of compounds and 4 (5) -aminomethylimidazole compounds, and therefore the method of the present invention is promising in the fields of medicine and agrochemicals.
【０００２】[0002]
【発明が解決しようとする課題】本発明者等は、既に新
規な4(5)−チオカルバモイル−イミダゾール化合物及び
その合成方法に関する出願を行っている。（特開平３−
１３５６９２号公報） しかしながら、前記公報に記載の製法では、イミダゾー
ル−ジチオカルボン酸化合物とアンモニア水溶液を密閉
容器中で加熱することを余儀なくされ、加熱反応によっ
て生じる圧力は低いけれども、密閉容器の使用が不可欠
である。本発明の目的は、このような4(5)−チオカルバ
モイル−イミダゾール化合物を合成するに当たり、この
密閉容器を必要としない方法を提案するものである。The present inventors have already filed an application for a novel 4 (5) -thiocarbamoyl-imidazole compound and its synthesis method. (JP-A-3-
However, in the production method described in the above publication, it is inevitable to heat the imidazole-dithiocarboxylic acid compound and the aqueous ammonia solution in a closed container, and although the pressure generated by the heating reaction is low, the use of a closed container is essential. Is. The object of the present invention is to propose a method which does not require this closed container in synthesizing such a 4 (5) -thiocarbamoyl-imidazole compound.
【０００３】[0003]
【課題を解決するための手段】本発明者等は、イミダゾ
ールジチオカルボン酸化合物に対して、アンモニア水溶
液の代わりにアンモニア発生剤として硫化アンモニウム
または多硫化アンモニウム水溶液を接触させて加熱すれ
ば、開放容器中でも反応は充分に進行することを知見
し、本発明方法を完遂するに至った。Means for Solving the Problems The present inventors have found that an imidazole dithiocarboxylic acid compound can be heated by contacting it with an ammonium sulfide or ammonium polysulfide aqueous solution as an ammonia generator instead of the ammonia aqueous solution, and heating it. Above all, they found that the reaction proceeded sufficiently, and completed the method of the present invention.
【０００４】硫化アンモニウムまたは多硫化アンモニウ
ムは単一物質ではなく、（ＮＨ4 ）2 Ｓx （但し、ｘは
１から５までの整数を表す）なる化合物の集合体と言わ
れている。例えば黄色を呈する硫化アンモニウム水溶液
は（ＮＨ4 ）2 Ｓを主成分とする多硫化アンモニウムの
集合体の水溶液であること、また赤褐色を呈する多硫化
アンモニウム水溶液は（ＮＨ4 ）2 Ｓ3 を主成分とする
集合体の水溶液であることが、夫々知られている（例え
ばザ・メルク・インデックス第９版，５８６頁参照）。Ammonium sulfide or ammonium polysulfide is not a single substance but is said to be an aggregate of compounds (NH 4 ) 2 S x (where x is an integer of 1 to 5). For example, a yellow ammonium sulfide aqueous solution is an aqueous solution of an ammonium polysulfide aggregate containing (NH 4 ) 2 S as a main component, and a reddish-brown ammonium polysulfide aqueous solution contains (NH 4 ) 2 S 3 as a main component. It is known that they are aqueous solutions of the aggregates (see, for example, The Merck Index, 9th Edition, page 586).
【０００５】（ＮＨ4 ）2 Ｓ5 は多硫化アンモニウムの
濃厚水溶液から単離されるが、それを水に溶かすと単体
硫黄を放出して（ＮＨ4 ）2 Ｓ3 水溶液を与えることが
知られている（千谷利三：新版無機化学，中巻，９３９
〜９４０頁：産業図書株式会社出版，昭和４８年版）。
他方、本発明者等の観察によれば、黄色の硫化アンモニ
ウム水溶液２５ml〔主成分（ＮＨ4 ）2 Ｓの２.5〜２.8
規定液〕は、８０℃以下の温度において、単体硫黄約
３.5ｇを溶解して、赤褐色に変色し一旦冷却しても単体
硫黄は析出しないことが判っている。これは（ＮＨ4 ）
2 Ｓが（ＮＨ4 ）2 Ｓ3 に変化したことを示す。Although (NH 4 ) 2 S 5 is isolated from a concentrated aqueous solution of ammonium polysulfide, it is known that when it is dissolved in water, elemental sulfur is released to give an (NH 4 ) 2 S 3 aqueous solution. (Rizo Chitani: New Edition Inorganic Chemistry, Nakamaki, 939
~ 940: Sangyo Tosho Co., Ltd., 1973 edition).
On the other hand, according to the observations of the present inventors, 25 ml of a yellow ammonium sulfide aqueous solution [main component (NH 4 ) 2 S 2.5 to 2.8]
It has been found that at a temperature of 80 ° C. or lower, about 3.5 g of elemental sulfur is dissolved, the color changes to reddish brown, and elemental sulfur does not precipitate even if cooled once. This is (NH 4 )
Indicates that 2 S is changed to (NH 4) 2 S 3.
【０００６】従って、本発明において使用される代表的
なアンモニア発生剤は、黄色硫化アンモニウム水溶液
〔（ＮＨ4 ）2 Ｓを主成分とする〕、赤色多硫化アンモ
ニウム水溶液〔（ＮＨ4 ）2 Ｓ3 を主成分とする〕ある
いは黄色硫化アンモニウム水溶液と単体硫黄の混合物の
３種類である。次に本発明の反応式について説明する。Therefore, typical ammonia generators used in the present invention are yellow ammonium sulfide aqueous solution [containing (NH 4 ) 2 S as a main component] and red ammonium polysulfide aqueous solution [(NH 4 ) 2 S 3 Or a mixture of yellow ammonium sulfide aqueous solution and elemental sulfur. Next, the reaction formula of the present invention will be described.
【０００７】[0007]
【化３】 [Chemical 3]
【０００８】（ＮＨ4 ）2 Ｓを主成分とする黄色硫化ア
ンモニウム水溶液を用いる場合、化３における硫化アン
モニウム化合物のｘは１であるから、反応により単体硫
黄は析出せず、その代わりにＮＨ4 ＳＨだけが生成する
ことになる。When a yellow ammonium sulfide aqueous solution containing (NH 4 ) 2 S as a main component is used, x in the ammonium sulfide compound in Chemical formula 3 is 1, so that elemental sulfur is not precipitated by the reaction, and NH 4 is used instead. Only SH will be generated.
【０００９】本発明方法の実施においては、硫化または
多硫化アンモニウムの使用量はジチオカルボン酸塩１モ
ルに対して２.5モル以上が好ましく、反応温度は反応系
の沸点程度が好適である。また、反応時間はジチオカル
ボン酸の種類によって異なるが一般的に６〜１４時間程
度である。ジチオカルボン酸の塩は、ジチオカルボン酸
に対し当量のアルカリ金属の塩（またはアルカリ土金属
の塩）を加えることにより容易に得られ、この場合の塩
としては水酸化物、炭酸化物及び重炭酸化物を意味して
いる。ジチオカルボン酸をそのまま反応に使用すること
もできるが、この場合は溶解するのに時間を要するの
で、直ちに系に溶解しうるジチオカルボン酸の塩にして
使用するほうが好ましい。In carrying out the method of the present invention, the amount of ammonium sulfide or polysulfide used is preferably 2.5 mol or more per 1 mol of dithiocarboxylic acid salt, and the reaction temperature is preferably about the boiling point of the reaction system. The reaction time varies depending on the type of dithiocarboxylic acid, but is generally about 6 to 14 hours. The salt of dithiocarboxylic acid can be easily obtained by adding an equivalent amount of the salt of alkali metal (or salt of alkaline earth metal) to dithiocarboxylic acid, and in this case, the salt includes hydroxide, carbonate and bicarbonate. Means a compound. The dithiocarboxylic acid can be used as it is in the reaction, but in this case it takes a long time to dissolve it, so it is preferable to use it as a salt of the dithiocarboxylic acid which can be immediately dissolved in the system.
【００１０】反応終了後、反応混合物を減圧乾固する
と、未反応の多硫化アンモニウムは分解してＮＨ4 ＳＨ
と単体硫黄になる。前者は系外に留出し、後者は系内に
残る。反応で生じたＮＨ4 ＳＨも同様留去される。従っ
て、乾固物は主に目的物チオカルバモイル化合物、単体
硫黄、未反応ジチオカルボン酸塩及び副反応生成物より
なるものである。After completion of the reaction, the reaction mixture was dried under reduced pressure to decompose unreacted ammonium polysulfide to NH 4 SH.
And become elemental sulfur. The former distills out of the system and the latter remains in the system. NH 4 SH generated in the reaction is also distilled off. Therefore, the dried product is mainly composed of the desired thiocarbamoyl compound, elemental sulfur, unreacted dithiocarboxylic acid salt and by-product.
【００１１】乾固物から目的物の単離は常法に従って行
われる。即ち、目的物が水に難溶の場合は、乾固物に少
量の水を加えて加熱後放冷し、析出する目的物と不溶の
単体硫黄を共に濾取し（未反応ジチオカルボン酸の塩は
水に易溶なので水相に移る）、濾取物に鉱酸水を加え単
体硫黄を濾別し（目的物の鉱酸塩は水に易溶、他方単体
硫黄は難溶）、次いで濾液を炭酸カリウムまたは炭酸ナ
トリウムによって中和したのち減圧乾固し、得られた乾
固物に少量の水を加えて一旦加熱放冷したのち、固形物
を濾取すると粗目的物が得られる（中和で生じた鉱酸塩
は水に易溶のため除去される）。順序を変え、乾固物に
最初から鉱酸水を加えて単体硫黄を予め濾別したのち、
前記の方法をとっても差し支えない。また中和後、減圧
乾固し、乾固物を熱エタノール抽出して粗目的物を得る
ことも可能である。The desired product is isolated from the dried product according to a conventional method. That is, when the target substance is poorly soluble in water, a small amount of water is added to the dry solid, heated and allowed to cool, and the target substance to be precipitated and insoluble elemental sulfur are collected by filtration (unreacted dithiocarboxylic acid Since the salt is easily soluble in water, it moves to the aqueous phase. Mineral acid water is added to the filtered material to separate the elemental sulfur by filtration (the desired mineral acid salt is easily soluble in water, while the elemental sulfur is sparingly soluble). The filtrate is neutralized with potassium carbonate or sodium carbonate, dried under reduced pressure, and a small amount of water is added to the obtained dry solid, and the mixture is once heated and allowed to cool, and the solid is collected by filtration to obtain a crude product ( The mineral salt generated by neutralization is easily dissolved in water and removed.) After changing the order and adding mineral acid water to the dry matter from the beginning to separate the elemental sulfur in advance,
The above method may be used. After neutralization, it is also possible to dry under reduced pressure and extract the dried product with hot ethanol to obtain the crude target product.
【００１２】他方、目的物が水に可溶の場合には、乾固
物に鉱酸水を加え、活性白土層を通過させたのち（未反
応ジチオカルボン酸は白土によく吸着され、単体硫黄は
同時に濾別される）、通過液を炭酸カリウムまたは炭酸
ナトリウムによって中和し、減圧乾固して粗目的物を乾
固物から熱アルコールによって抽出する。以下、本発明
方法を実施例によって具体的に説明する。On the other hand, when the target substance is soluble in water, mineral acid water is added to the dried solid matter and allowed to pass through the activated clay layer (the unreacted dithiocarboxylic acid is well adsorbed on the clay and elemental sulfur is used). Are filtered off at the same time), the passing solution is neutralized with potassium carbonate or sodium carbonate, dried under reduced pressure and the crude product is extracted from the dried product with hot alcohol. Hereinafter, the method of the present invention will be specifically described with reference to examples.
【００１３】[0013]
【実施例１】イミダゾール−４−ジチオカルボン酸0.０
２モル(2.9g)に１Ｎ−ＮａＯＨ２０mlを加えたのち、市
販黄色硫化アンモニウム水溶液（約２.5規定）３０mlを
加え、還流器を備えたフラスコ中で８５〜９０℃の反応
温度で８時間加熱を行った。次いで未反応硫化アンモニ
ウムを除去するため、反応混合物を減圧乾固し、その乾
固物に適当量の水と６Ｎ塩酸１２ml（ＮａＯＨ中和のた
め）を加えて不溶物（主に単体硫黄）を濾別し、未反応
ジチオカルボン酸を除去するため濾液を１０ｇの活性白
土層で通過処理し、通過液を再び別の１０ｇの活性白土
層処理し、得られた通過液を炭酸カリウムで中和したの
ち減圧乾固に付し、乾固物を熱メタノール抽出し、抽出
液を乾固して乾固物の形で粗目的物４−チオカルバモイ
ルイミダゾールを0.１５モル(2.0g)を得た。（収率は７
７モル％）Example 1 Imidazole-4-dithiocarboxylic acid 0.0
After adding 20 ml of 1N-NaOH to 2 mol (2.9 g), 30 ml of a commercially available aqueous solution of yellow ammonium sulfide (about 2.5 N) was added and heated in a flask equipped with a reflux condenser at a reaction temperature of 85 to 90 ° C. for 8 hours. I went. Then, in order to remove unreacted ammonium sulfide, the reaction mixture was dried under reduced pressure, and an appropriate amount of water and 12 ml of 6N hydrochloric acid (for neutralization of NaOH) were added to the dried mixture to remove insoluble matter (mainly elemental sulfur). The filtrate was filtered off to remove unreacted dithiocarboxylic acid, and the filtrate was passed through with 10 g of an activated clay layer, the passed liquid was treated with another 10 g of an activated clay layer again, and the obtained passing liquid was neutralized with potassium carbonate. After that, the mixture was subjected to reduced pressure dryness, and the dry solid was extracted with hot methanol, and the extract was dried to dryness to obtain 0.15 mol (2.0 g) of the crude target product 4-thiocarbamoylimidazole in the form of a dry solid. It was (Yield is 7
7 mol%)
【００１４】[0014]
【実施例２】２−メチルイミダゾール−４−ジチオカル
ボン酸0.０２モル(3.2g)に１Ｎ−ＮａＯＨ２０mlと市販
の黄色硫化アンモニウム水溶液（約２.5規定）３０mlを
加え、８９℃の温度で６時間加熱したのち、実施例１と
同様の後処理を行い、粗目的物４−チオカルバモイル−
２−メチルイミダゾールを0.１６モル(2.3g)得た。（収
率は８０モル％）EXAMPLE 2 To 0.02 mol (3.2 g) of 2-methylimidazole-4-dithiocarboxylic acid was added 20 ml of 1N-NaOH and 30 ml of a commercially available yellow ammonium sulfide aqueous solution (about 2.5 N) at a temperature of 89 ° C. After heating for 6 hours, the same post-treatment as in Example 1 was performed to obtain the crude target product 4-thiocarbamoyl-
0.16 mol (2.3 g) of 2-methylimidazole was obtained. (Yield is 80 mol%)
【００１５】[0015]
【実施例３】２−エチルイミダゾール−４−ジチオカル
ボン酸0.０２モル(3.4g)、１Ｎ−ＮａＯＨ２０ml及び黄
色硫化アンモニウム水溶液（約２.5規定）３０mlの三者
を９０℃の温度で１４時間加熱したのち、実施例１と同
様の後処理を行い、粗目的物４−チオカルバモイル−２
−エチルイミダゾールを0.１５モル(2.3g)得た。（収率
は７４モル％）EXAMPLE 3 2-Ethylimidazole-4-dithiocarboxylic acid 0.02 mol (3.4 g), 1N NaOH (20 ml) and yellow ammonium sulfide aqueous solution (about 2.5 N) (30 ml) were mixed at a temperature of 90 ° C. After heating for a time, the same post-treatment as in Example 1 was carried out to give the crude target product 4-thiocarbamoyl-2.
0.15 mol (2.3 g) of -ethylimidazole was obtained. (Yield is 74 mol%)
【００１６】[0016]
【実施例４】２−イソプロピルイミダゾール−４−ジチ
オカルボン酸0.０２モル(3.7g)、１Ｎ−ＮａＯＨ２０ml
及び黄色硫化アンモニウム水溶液（約２.5規定）３０ml
の三者を９０℃の温度で６時間加熱したのち、実施例１
と同様の後処理を行い、粗目的物４−チオカルバモイル
−２−イソプロピルイミダゾールを0.０８モル(1.4g)得
た。（収率は４１モル％）Example 4 2-isopropylimidazole-4-dithiocarboxylic acid 0.02 mol (3.7 g), 1N NaOH 20 ml
And yellow ammonium sulfide aqueous solution (about 2.5N) 30ml
Example 3 was heated at 90 ° C. for 6 hours.
The post-treatment was carried out in the same manner as in (4) above to obtain 0.08 mol (1.4 g) of the crude target product 4-thiocarbamoyl-2-isopropylimidazole. (Yield is 41 mol%)
【００１７】[0017]
【実施例５】２−ｎ−ウンデシルイミダゾール−４−ジ
チオカルボン酸0.０２モル(6.0g)、１Ｎ−ＮａＯＨ２０
ml及び黄色硫化アンモニウム水溶液（約２.5規定）３０
mlの三者を８５〜９３℃の温度で８時間加熱したのち、
実施例１と同様の後処理を行い、粗目的物４−チオカル
バモイル−２−ｎ−ウンデシルイミダゾールを0.１４モ
ル(4.0g)得た。（収率は７１モル％）Example 5 2-n-undecylimidazole-4-dithiocarboxylic acid 0.02 mol (6.0 g), 1N-NaOH 20
ml and yellow ammonium sulfide aqueous solution (about 2.5 normal) 30
After heating the 3 mls at 85-93 ° C for 8 hours,
The same post-treatment as in Example 1 was carried out to obtain 0.14 mol (4.0 g) of the crude target product 4-thiocarbamoyl-2-n-undecylimidazole. (Yield 71 mol%)
【００１８】[0018]
【実施例６】２−ｎ−ヘプタデシルイミダゾール−４−
ジチオカルボン酸0.０２モル(7.6g)、１Ｎ−ＮａＯＨ２
０ml、水１０ml及び黄色硫化アンモニウム水溶液（約
２.5規定）３０mlの四者を８５〜９２℃の温度で８時間
加熱したのち、実施例１と同様の後処理を行い、粗目的
物４−チオカルバモイル−２−ｎ−ヘプタデシルイミダ
ゾールを0.１６モル(6.0g)得た。（収率は８２モル％）Example 6 2-n-heptadecyl imidazole-4-
Dithiocarboxylic acid 0.02 mol (7.6 g), 1N-NaOH2
Four ml of 0 ml, 10 ml of water and 30 ml of a yellow ammonium sulfide aqueous solution (about 2.5 N) were heated at a temperature of 85 to 92 ° C. for 8 hours, and then post-treated in the same manner as in Example 1 to give the crude product 4-. Thiocarbamoyl-2-n-heptadecyl imidazole (0.16 mol, 6.0 g) was obtained. (Yield 82 mol%)
【００１９】[0019]
【実施例７】4(5)−メチルイミダゾール−5(4)−ジチオ
カルボン酸0.０２モル(3.2g)、１Ｎ−ＮａＯＨ２０ml、
単体硫黄４ｇ及び黄色硫化アンモニウム水溶液（約２.5
規定）３０mlの四者を８９〜９４℃の温度で６時間加熱
した。反応混合物を減圧乾固し、乾固物に水１０mlを加
え煮沸放冷し、第１結晶を濾取し、第１濾液を減圧濃縮
して第２結晶を濾取して、第１結晶と第２結晶を合併し
たのち、これに塩酸水溶液を充分に加え、単体硫黄を濾
別し、濾液を活性炭層通過処理し、通過液を減圧乾固に
付し、乾固物を水で再結晶して粗目的物4(5)−チオカル
バモイル−5(4)−メチルイミダゾール塩酸塩を0.１４モ
ル(2.4g)得た。（収率は６８モル％）Example 7 4 (5) -Methylimidazole-5 (4) -dithiocarboxylic acid 0.02 mol (3.2 g), 1N-NaOH 20 ml,
4 g of elemental sulfur and yellow ammonium sulfide aqueous solution (about 2.5
(Regular) 30 ml of each was heated at a temperature of 89-94 ° C for 6 hours. The reaction mixture was dried under reduced pressure, 10 ml of water was added to the dried solid, and the mixture was boiled and cooled. The first crystal was collected by filtration, the first filtrate was concentrated under reduced pressure, and the second crystal was collected by filtration to obtain the first crystal. After merging the second crystal, an aqueous hydrochloric acid solution was sufficiently added to this, elemental sulfur was filtered off, the filtrate was passed through an activated carbon layer, the passing solution was dried under reduced pressure, and the dried solid was recrystallized with water. Thus, 0.14 mol (2.4 g) of the crude product 4 (5) -thiocarbamoyl-5 (4) -methylimidazole hydrochloride was obtained. (Yield is 68 mol%)
【００２０】[0020]
【実施例８】2,4(5)−ジメチルイミダゾール−5(4)−ジ
チオカルボン酸0.０２モル(3.4g)、１Ｎ−ＮａＯＨ２０
ml、水５ml及び黄色硫化アンモニウム水溶液（約２.5規
定）３０mlの四者を８９〜９２℃の温度で１０時間加熱
したのち、実施例１と同様の後処理を行い、粗目的物5
(4)−チオカルバモイル−2,4(5)−ジメチルイミダゾー
ルを0.１２モル(1.8g)得た。（収率は５８モル％）Example 8 2,4 (5) -Dimethylimidazole-5 (4) -dithiocarboxylic acid 0.02 mol (3.4 g), 1N-NaOH 20
4 ml of water, 5 ml of water and 30 ml of a yellow ammonium sulfide aqueous solution (about 2.5 N) were heated at a temperature of 89 to 92 ° C. for 10 hours, and then post-treated in the same manner as in Example 1 to give the crude product 5.
0.12 mol (1.8 g) of (4) -thiocarbamoyl-2,4 (5) -dimethylimidazole was obtained. (Yield is 58 mol%)
【００２１】[0021]
【実施例９】２−エチル−4(5)−メチルイミダゾール−
5(4)−ジチオカルボン酸0.０２モル(3.7g)、Ｋ2 ＣＯ3
0.０２モル(2.8g)、水２０ml及び黄色硫化アンモニウム
水溶液（約２.5規定）３０mlの四者を８８〜１００℃の
温度で１２時間加熱したのち、実施例１と同様の後処理
を行い、粗目的物5(4)−チオカルバモイル−２−エチル
−4(5)−メチルイミダゾールを0.０７モル(1.2g)得た。
（収率は３４モル％）Example 9 2-Ethyl-4 (5) -methylimidazole-
5 (4) -dithiocarboxylic acid 0.02 mol (3.7 g), K 2 CO 3
After heating 0.04 mol (2.8 g), 20 ml of water and 30 ml of a yellow ammonium sulfide aqueous solution (about 2.5 N) at a temperature of 88 to 100 ° C. for 12 hours, the same post-treatment as in Example 1 was performed. This was carried out to obtain 0.07 mol (1.2 g) of the crude product 5 (4) -thiocarbamoyl-2-ethyl-4 (5) -methylimidazole.
(Yield is 34 mol%)
【００２２】[0022]
【実施例１０】２−フェニルイミダゾール−４−ジチオ
カルボン酸0.０２モル(4.4g)、１Ｎ−ＮａＯＨ２０ml及
び黄色硫化アンモニウム水溶液（約２.5規定）３０mlの
三者を８７℃の温度で１２時間加熱したのち、実施例１
と同様の後処理を行い、粗目的物４−チオカルバモイル
−２−フェニルイミダゾールを0.１２モル(2.4g)得た。
（収率は６０モル％）Example 10 2-Phenylimidazole-4-dithiocarboxylic acid 0.02 mol (4.4 g), 1N NaOH (20 ml) and yellow ammonium sulfide aqueous solution (about 2.5 N) (30 ml) were mixed at a temperature of 87 ° C. After heating for an hour, Example 1
The same post-treatment was carried out as above to obtain 0.12 mol (2.4 g) of the crude target product 4-thiocarbamoyl-2-phenylimidazole.
(Yield is 60 mol%)
Claims (1)
ロピル基、フェニル基、ｎ−ウンデシル基またはｎ−ヘ
プタデシル基、Ｒ4 は水素原子またはメチル基、Ｍは水
素、ナトリウム、カリウム、カルシウムまたはバリウム
の各原子を表す）で示されるイミダゾール−ジチオカル
ボン酸化合物と硫化アンモニウムあるいは多硫化アンモ
ニウム水溶液を加熱反応させることを特徴とする 【化２】 （但し、Ｒ2 及びＲ4 は前記と同じである）で示される
4(5)−チオカルバモイル−イミダゾール化合物の合成方
法。Claims: (However, R 2 is a hydrogen atom, methyl group, ethyl group, isopropyl group, phenyl group, n-undecyl group or n-heptadecyl group, R 4 is a hydrogen atom or a methyl group, M is hydrogen, sodium, potassium, calcium or (Representing each atom of barium) is characterized by reacting an imidazole-dithiocarboxylic acid compound represented by (Provided that R 2 and R 4 are the same as above)
Method for synthesizing 4 (5) -thiocarbamoyl-imidazole compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03335794A JP3110830B2 (en) | 1991-10-02 | 1991-10-02 | Method for synthesizing 4 (5) -thiocarbamoyl-imidazole compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03335794A JP3110830B2 (en) | 1991-10-02 | 1991-10-02 | Method for synthesizing 4 (5) -thiocarbamoyl-imidazole compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0597815A true JPH0597815A (en) | 1993-04-20 |
| JP3110830B2 JP3110830B2 (en) | 2000-11-20 |
Family
ID=18292507
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03335794A Expired - Fee Related JP3110830B2 (en) | 1991-10-02 | 1991-10-02 | Method for synthesizing 4 (5) -thiocarbamoyl-imidazole compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3110830B2 (en) |
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- 1991-10-02 JP JP03335794A patent/JP3110830B2/en not_active Expired - Fee Related
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| Publication number | Publication date |
|---|---|
| JP3110830B2 (en) | 2000-11-20 |
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