JPH0643403B2 - Method for synthesizing imidazole-aldoxime compounds - Google Patents
Method for synthesizing imidazole-aldoxime compoundsInfo
- Publication number
- JPH0643403B2 JPH0643403B2 JP61014286A JP1428686A JPH0643403B2 JP H0643403 B2 JPH0643403 B2 JP H0643403B2 JP 61014286 A JP61014286 A JP 61014286A JP 1428686 A JP1428686 A JP 1428686A JP H0643403 B2 JPH0643403 B2 JP H0643403B2
- Authority
- JP
- Japan
- Prior art keywords
- mol
- imidazole
- aldoxime
- water
- acetic acid
- 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 - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 10
- 230000002194 synthesizing effect Effects 0.000 title claims description 3
- UFKWQRUCZNBSDY-UHFFFAOYSA-N N-(1H-imidazol-2-ylmethylidene)hydroxylamine Chemical class ON=CC1=NC=CN1 UFKWQRUCZNBSDY-UHFFFAOYSA-N 0.000 title description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 45
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 38
- -1 imidazole-dithiocarboxylic acid compound Chemical class 0.000 claims description 25
- 238000010992 reflux Methods 0.000 claims description 11
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 8
- 239000001632 sodium acetate Substances 0.000 claims description 8
- 235000017281 sodium acetate Nutrition 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- IQZFEWXBHUWSDX-UHFFFAOYSA-N 1h-imidazole-2-carbodithioic acid Chemical compound SC(=S)C1=NC=CN1 IQZFEWXBHUWSDX-UHFFFAOYSA-N 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 238000001914 filtration Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- AXJZCJSXNZZMDU-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanol Chemical compound CC=1N=CNC=1CO AXJZCJSXNZZMDU-UHFFFAOYSA-N 0.000 description 3
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 3
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical compound O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N Histidine Chemical compound OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- VZEMVZZNSNMEPJ-UHFFFAOYSA-N N-(1H-imidazol-5-ylmethylidene)hydroxylamine Chemical compound ON=CC1=CN=CN1 VZEMVZZNSNMEPJ-UHFFFAOYSA-N 0.000 description 2
- NLJYUXHUESWCOS-UHFFFAOYSA-N N-[(2-methyl-1H-imidazol-5-yl)methylidene]hydroxylamine Chemical compound Cc1ncc(C=NO)[nH]1 NLJYUXHUESWCOS-UHFFFAOYSA-N 0.000 description 2
- FZTHQGWRXISGFS-UHFFFAOYSA-N N-[(2-phenyl-1H-imidazol-5-yl)methylidene]hydroxylamine Chemical compound ON=Cc1cnc([nH]1)-c1ccccc1 FZTHQGWRXISGFS-UHFFFAOYSA-N 0.000 description 2
- DRLHVAWTAGOTAU-UHFFFAOYSA-N N-[(5-methyl-1H-imidazol-4-yl)methylidene]hydroxylamine Chemical compound CC=1N=CNC=1C=NO DRLHVAWTAGOTAU-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- 238000006887 Ullmann reaction Methods 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002481 ethanol extraction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical class OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 description 1
- WQKQGRXNHYXVAH-UHFFFAOYSA-N 2-ethyl-5-methyl-1h-imidazole-4-carbodithioic acid Chemical compound CCC1=NC(C(S)=S)=C(C)N1 WQKQGRXNHYXVAH-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
- CLZLWWMCFNJWMN-UHFFFAOYSA-N 2-sulfanyl-2h-1,3-thiazol-5-one Chemical compound SC1SC(=O)C=N1 CLZLWWMCFNJWMN-UHFFFAOYSA-N 0.000 description 1
- KMWCSNCNHSEXIF-UHFFFAOYSA-N 5-methyl-1h-imidazole-4-carbaldehyde Chemical compound CC=1N=CNC=1C=O KMWCSNCNHSEXIF-UHFFFAOYSA-N 0.000 description 1
- FWWVSTJJEPANBO-UHFFFAOYSA-N 5-methyl-1h-imidazole-4-carbodithioic acid Chemical compound CC=1NC=NC=1C(S)=S FWWVSTJJEPANBO-UHFFFAOYSA-N 0.000 description 1
- FNKXLEZIGQBFIA-UHFFFAOYSA-N 5-methyl-2-phenyl-1h-imidazole-4-carbodithioic acid Chemical compound SC(=S)C1=C(C)NC(C=2C=CC=CC=2)=N1 FNKXLEZIGQBFIA-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 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
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- VLDUBDZWWNLZCU-UHFFFAOYSA-N ethyl 5-methyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC=NC=1C VLDUBDZWWNLZCU-UHFFFAOYSA-N 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Description
【発明の詳細な説明】 本発明は、イミダゾール−アルドキシム化合物の合成方
法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing imidazole-aldoxime compounds.
産業上の利用分野 本発明の方法でえられるイミダゾール−アルドキシム化
合物は、生化学あるいは医薬分野において重要な意味を
持つ各種のイミダゾール化合物の出発原料として使用出
来る有用な化合物である。それらを次に例示する。INDUSTRIAL APPLICABILITY The imidazole-aldoxime compound obtained by the method of the present invention is a useful compound that can be used as a starting material for various imidazole compounds that have important meanings in the biochemical or pharmaceutical fields. They are illustrated below.
生化学上重要なＬ−ヒスチヂンは半必須アミノ酸で、今
日蛋白質の分解により作られている。この蛋白質として
ヘモグロビンが使用されている〔H.B.Vickery：J.Biol.
Chem 143,77(1942)；ジャーナル，オブ，バイオロジカ
ル，ケミストリー第143巻，第77頁，1942年〕。他方、
生化学上重要なＤＬ−ヒスチヂンは本発明方法によって
えられるイミダゾール−アルドキシム化合物の一つ即
ち、イミダゾール−４−アルドキシムの鉱酸水溶液によ
る加水分解で容易に得られる４−フォルミル−イミダゾ
ールと馬尿酸から合成される〔F.L.Pyman：J.C.S.,109,
186(1916)；ジャーナル，オブ，ケミカル，ソサイアト
ゥイー第109巻，第186頁，1916年〕。L-histidine, which is important in biochemistry, is a semi-essential amino acid and is produced today by protein degradation. Hemoglobin is used as this protein [HBVickery: J. Biol.
Chem 143,77 (1942); Journal, Of, Biological, Chemistry Vol. 143, p. 77, 1942]. On the other hand,
DL-histidine, which is important in biochemistry, is one of the imidazole-aldoxime compounds obtained by the method of the present invention, namely 4-formyl-imidazole and hippuric acid, which are easily obtained by hydrolysis of imidazole-4-aldoxime with an aqueous mineral acid solution. Synthesized [FLPyman: JCS, 109,
186 (1916); Journal, Of, Chemical, Society of Vol. 109, 186, 1916].
このものは４−フォルミル−イミダゾールとヒダントイ
ンからも同じく合成される〔V.Deulofeuら：J.O.C.,14,
915(1949)；ジャーナル，オブ，オーギャニック，ケミ
ストリー第14巻，第915頁，1949年〕。It is also synthesized from 4-formyl-imidazole and hydantoin [V. Deulofeu et al .: JOC, 14,
915 (1949); Journal, Of, Organic, Chemistry Vol. 14, p. 915, 1949].
また、このものは４−フォルミル−イミダゾールと２−
メルカブト−５−チアゾロンからも合成出来る〔A.C.Da
visら：J.C.S.,2179(1949)；ジャーナル，オブ，ケミカ
ル，ソサイアトゥイー第2179頁，1949年〕。Also, this product has 4-formyl-imidazole and 2-
It can also be synthesized from mercapto-5-thiazolone [ACDa
vis et al .: JCS, 2179 (1949); Journal, Of, Chemical, Sociateui, 2179, 1949].
他方、神経性胃潰瘍治療薬として有用なシメチジンの
出発原料４−メチル−５−ヒドロキシメチル−イミダゾ
ールは４−メチル−５−エトキシカルボニルイミダゾー
ルの液体アンモニア中における金属ナトリウムによる還
元によって1978年において年間約300トン生産されたこ
とが知られている〔Ullmanns Encyklopadie der techni
schen Chemie 4.,neubearbeitete und erweiterte Aufl
age Band 20,s.139(Verlag Chemie)；ウルマンス，エン
ツアイクロペドウイ，デア，テヒニッシェン，ヘミー，
４．，ノイベアルバイテテ，オント，エアヴァイタァ
テ，アウフラーゲ 第20巻，第139頁（フェアラーク
ヘミー出版）〕。On the other hand, 4-methyl-5-hydroxymethyl-imidazole, a starting material of cimetidine, which is useful as a therapeutic drug for neurological gastric ulcer, has a concentration of about 300 per year in 1978 by reduction of 4-methyl-5-ethoxycarbonylimidazole with sodium metal in liquid ammonia. Known to have been produced [Ullmanns Encyklopadie der techni
schen Chemie 4., neubearbeitete und erweiterte Aufl
age Band 20, s.139 (Verlag Chemie); Ullmanns, Enz Ai Clopedoui, Der, Taehinischen, Hemy,
4. , Neube Albaitete, Ont, Ervayate, Aufrage Volume 20, 139 (Fairark
Hemy Publishing)].
この４−メチル−５−ヒドロシキメチル−イミダゾール
は本発明方法によってえられるイミダゾール−アルドキ
シム化合物の一つ、即ち４−メチルイミダゾール−５−
アルドキシムの鉱酸水溶液による加水分解で容易にえら
れる４−メチル−５−フォルミル−イミダゾールの常法
の還元法によって簡単にえられる化合物である。４−メ
チル−５−ヒドロキシメチル−イミダゾールの性質は次
のとおりである。融点：136〜138℃；TLC（シリカＧ、E
tOH、Ｉ2発色）：Rf0.4〜0.5；NMR(CF3COOD)：δ8.61,
S,1H；5.53,S,2H；2.56,S,3H；Mass:m/e112,111,95,94,
83,81,70,69,…52，…42， イミダゾール−アルドキシム化合物は鉱酸水溶液と反応
し容易にフォルミル−イミダゾール化合物を与える事に
ついて前述したが、フォルミル−イミダゾール化合物は
過酸酸化で生化学上有用な各種のイミダゾール−カルボ
ン酸をさらに与えることも知られている。This 4-methyl-5-hydroxymethyl-imidazole is one of the imidazole-aldoxime compounds obtained by the method of the present invention, namely 4-methylimidazole-5-.
It is a compound easily obtained by a conventional reduction method of 4-methyl-5-formyl-imidazole which is easily obtained by hydrolysis of aldoxime with an aqueous solution of mineral acid. The properties of 4-methyl-5-hydroxymethyl-imidazole are as follows. Melting point: 136-138 ° C; TLC (silica G, E
tOH, I 2 color development): Rf 0.4 to 0.5; NMR (CF 3 COOD): δ8.61,
S, 1H; 5.53, S, 2H; 2.56, S, 3H; Mass: m / e112,111,95,94,
83,81,70,69, ... 52, ... 42, Although the imidazole-aldoxime compound reacts with an aqueous solution of a mineral acid to easily give a formyl-imidazole compound, the formyl-imidazole compound can further give various imidazole-carboxylic acids useful in biochemistry by peracid oxidation. Are known.
イミダゾールのアルドキシム基は還元により容易にアミ
ノメチル基を与えることも知られている。It is also known that the aldoxime group of imidazole easily gives an aminomethyl group by reduction.
このように本発明の方法でえられるイミダゾール−アル
ドキシム化合物は研究用試薬として使用出来る化合物で
ある。Thus, the imidazole-aldoxime compound obtained by the method of the present invention is a compound that can be used as a research reagent.
発明が解決しようとする問題点 生化学あるいは医薬分野において重要な意味を持つ各種
のイミダゾール化合物の出発原料としてのある種のイミ
ダゾール−アルドキシム化合物は、従来の方法では合成
に手間のかかる甚だ入手困難な化合物であり、それらの
簡単な合成方法の出現が望まれて来た。Problems to be Solved by the Invention Certain imidazole-aldoxime compounds as starting materials for various imidazole compounds, which have important meanings in biochemistry or pharmaceutical fields, are difficult to obtain by conventional methods and are difficult to obtain. Compounds, the advent of simple synthetic methods for them has been desired.
また、イミダゾール−アルドキシム化合物の近縁体はこ
れ迄殆ど上市されたことがなく、従って研究用試薬とし
てのそれら近縁体の提供が望まれて来た。In addition, related compounds of imidazole-aldoxime compounds have rarely been put on the market until now, and therefore it has been desired to provide them as research reagents.
問題点を解決するための手段 本発明者等は前記の問題点を、イミダゾール−アルドキ
シム化合物の提供によって解決しようとするものであ
る。Means for Solving the Problems The present inventors intend to solve the above problems by providing an imidazole-aldoxime compound.
本発明者等はイミダゾールと二硫化炭素よりえられるイ
ミダゾール−ジチオカルボン酸化合物（特公昭69-29707
号公報参照）が醋酸ナトリウムと醋酸の存在下において
塩酸ヒドロキシルアミンの作用でイミダゾール−アルド
キシム化合物を与えることを見い出した。The present inventors have found that an imidazole-dithiocarboxylic acid compound obtained from imidazole and carbon disulfide (Japanese Patent Publication No. 69-29707).
(See Japanese Laid-Open Patent Publication No. 2003-242242) to give an imidazole-aldoxime compound by the action of hydroxylamine hydrochloride in the presence of sodium acetic acid and acetic acid.
このようにイミダゾール−ジチオカルボン酸化合物が容
易に硫黄を放出し、イミダゾール−アルドキシム化合物
を与える反応は全く新規である。Thus, the reaction in which an imidazole-dithiocarboxylic acid compound easily releases sulfur to give an imidazole-aldoxime compound is completely novel.
この反応によって本発明者等は前記の各問題を解決する
ことが出来た。また、この反応により新規なイミダゾー
ル−アルドキシム化合物の提供が可能となった。The present inventors were able to solve each of the above problems by this reaction. In addition, this reaction made it possible to provide a novel imidazole-aldoxime compound.
実施の態様 本発明の実施の態様は簡単である。即ち１モルのイミダ
ゾール−ジチオカルボン酸化合物、1.5モル以上の醋酸
ナトリウムおよび塩酸ヒドロキシアミンおよび適当量の
醋酸または含水醋酸の４者からなる系を加熱還流し、反
応系を冷却し、不溶物を濾別し、濾液を活性炭処理した
のち減圧乾固し、乾固物をアルカリ水溶液で中和し、析
出結晶を濾取する。かくしてえられる粗目的物イミダゾ
ール−アルドキシム化合物は、必要に応じ、常法の再結
晶または減圧蒸留によって精製される。Embodiments Embodiments of the present invention are simple. That is, a system consisting of 1 mol of an imidazole-dithiocarboxylic acid compound, 1.5 mol or more of sodium acetic acid and hydroxyamine hydrochloride, and an appropriate amount of acetic acid or hydrous acetic acid is heated to reflux, the reaction system is cooled, and the insoluble matter is filtered off. Separately, the filtrate is treated with activated carbon, dried under reduced pressure, the dried product is neutralized with an aqueous alkali solution, and the precipitated crystals are collected by filtration. The crude imidazole-aldoxime compound thus obtained is purified by recrystallization or vacuum distillation according to a conventional method, if necessary.
本発明の方法によってえられるイミダゾール−アルドキ
シム化合物の性質を次示する。The properties of the imidazole-aldoxime compound obtained by the method of the present invention are shown below.
イミダゾール−４−アルドキシム 弱塩基性無色結晶。m.P.181〜183℃（水）；水、アルコ
ールおよびアセトンに可溶；TLC（シリカＧ，アセト
ン，I2発色）：Rf0.53〜0.65 （カッコ内は透過率％を示す、以下同様） NMR(d6-DMSO) ： δ 12.28,S,1H(-NH-)；11.37,S,1H（＝N-OH)；7.6
7,S,1H（＝C-CH＝）；7.67,S,1H（２位プロトン）；7.3
5,S,1H（５位プロトン） Mass：m/e 111(m+),84,67,52,39 ２−メチルイミダゾール−４−アルドキシム 塩基性無色結晶。m.P.163〜164℃（水）；メタノール、
およびエタノールに易溶、熱水に可溶；TLC（シリカ
Ｇ、エタノール、I2発色）：Rf0.59〜0.66 NMR(CD3OD) ： δ 7.61,S,1H(-CH＝N-)；7.29,S,1H（５位）；2.3
6,S,3H（メチル） Mass：m/e125(M+),108(M+-OH),107(M+-H2O),82,81,66,5
4,41 ２−エチルイミダゾール−４−アルドキシム 弱塩基性無色結晶。m.P.173〜175℃（水）；水、アルコ
ールおよびアセトンに可溶；TLC（シリカＧ、アセト
ン、I2発色）：Rf0.41〜0.52 NMR(CD3OD) ： δ 7.92,S,1H（アンチ型-CH＝N-),7.62,S（５
位），7.31,S（シン型-CH＝N-),7.08,S（５位），計2
H；2.72,q（２位メチレン），2.68（２位メチレン）計2
H;1.27,t（２位メチル），1.26,t（２位メチル），計3H Mass：m/e 139(M+),124,(M+-CH3),122(M+-OH),95,94,79 ２−ウンデシルイミダゾール−４−アルドキシム 中性無色結晶。m.P.148〜154℃（醋酸エチル）；メタノ
ールおよびエタノールに易溶、醋酸エチル、アセトンお
よびクロロフォルムに熱時可溶、水に不溶；TLC（シリ
カＧ、エタノール、I2発色）：Rf0.76〜0.86 NMR(CD3OD) ： δ 7.61,S,1H(-CH＝N-)；7.28,S,1H（５位）；2.6
9,t,2H（α−メチレン）；1.68,br.m,2H（β−メチレ
ン）；1.27,S,16H（中間メチレン群）；0.88,t,3H（末
端メチル） Mass：m/e 265(M+),248,(M+-OH),235(M+-C2H5),222(M+-
C3H7),208(M+-C4H9),194,180,166,152,138,125,107,94,
80,55,41 ２−ヘプタデシルイミダゾール−４−アルドキシム 中性無色結晶。m.P.142〜149℃（エタノール）DMSOに可
溶、メタノールおよびエタノールに熱時可溶、水に不
溶；TLC（シリカＧ、エタノール、I2発色）：Rf0.68〜
0.77 NMR(d6-DMSO) ： δ 7.52,S,1H(-CH＝N-)；7.26,S,1H（５位）；2.5
7,t（α−メチレン）；1.58,br.S,2H（β−メチレ
ン）；1.22,S,28H（中間メチレン群）；0.84,br.t,3H
（末端メチル） Mass：m/e 349(M+),332(M+-OH),331(M+-H2O),320,306,2
92,278,264,250,236,222,208,194,180,163,138,125,12
0,107,80,57,55,42 ２−フェニルイミダゾール−４−アルドキシム 淡黄色塩基性結晶。m.P.184〜186℃（水）；メタノール
およびアセントに易溶、熱水に可溶；TLC（シリカＧ、
エタノール、B.T.B.発色）：Rf0.65〜0.75 NMR(CD3OD) ： δ 8.03,S,0.4H（４位）；7.82,m,2.4H（フェニ
ル）；7.43,m,3.6H（フェニルと-CH＝N-)；7.33,S,0.6H
（４位） Mass：m/e 187(M+),170(M+-OH),144,115,104,77 ４−メチルイミダゾール−５−アルドキシム 弱塩基性無色結晶。m.P.90〜108℃で融け、ついで固化
し、147〜153で再び融ける。メタノール、エタノールお
よびDMSOに易溶、熱水に可溶；TLC（シリカＧ、エタノ
ール、I2発色）：Rf0.58〜0.68 NRM(CD3OD) ： δ 8.03,S,（アンチ型-CH＝N-),7.62,S（シン
型），計1H；7.54,S,7.36,S,計1H（２位）；2.28,S,3H
（メチル） Mass：m/e 125(M+),108(M+-OH),81(M+-CH＝N-OH),66,5
4,53,52 ２−エチル−４−メチルイミダゾール−５−アルドキシ
ム 塩基性無色結晶。m.P.205〜207℃（水）；熱水、エタノ
ールおよびアセトンに易溶；TLC（シリカＧ、エタノー
ル、I2発色） NMR(CD3OD) ： δ 7.95,と7.25,S,計1H(-CH＝N-)；2.72;と2.64,
q,計2H（α−メチレン）；2.24と2.22,S,計3H（４位メ
チル）；1.24,t,3H（２位の末端メチル） Mass：m/e153(M+),136(M+-OH),109 ２，４−ジメチルイミダゾール−５−アルドキシム 塩基性無色結晶。m.P.48〜49℃（水）；アルコール、ア
セトンおよび熱水に易溶；TLC（シリカＧ、エタノー
ル、I2発色）：Rf0.55〜0.70 NMR(D2O) ： δ 7.98と7.32,S,計1H(-CH＝N-)；2.32と2.28,S,
計3H（２位メチル）；2.19と2.18,S,計3H（４位メチ
ル） Mss：m/e 139(M+),122(M+-OH),95２−フェニル−４−メ
チルイミダゾール−５−アルドキシム 弱塩基性無色結晶。m.P.205〜207℃(CH3CN)；メタノー
ルおよびアセトンに可溶、水に難溶；TLC（シリカＧ、
アセトン、I2発色）：Rf0.86〜0.75 NMR(CD3OD) ： δ 8.06,s,1H(-CH＝N-)；7.9〜7.2,m,5H（フェニ
ル）；2.36,S,3H（メチル） Mass：m/e201(M+),184(M+-OH),170(M+-NOH),157,115,10
4,77 実施例１ イミダゾール−４−ジチオカルボン酸0.1モル(15ｇ），
95％塩酸ヒドロキシルアミン0.1モル（7.6ｇ），醋酸ナ
トリウム0.1モル（8.5ｇ）および醋酸40mlの４者からな
る系を40分間加熱還流し、ついで95％塩酸ヒドロキシル
アミン0.05モル（3.8ｇ）および醋酸ナトリウム0.05モ
ル（4.3ｇ）を加え、さらに１時間20分加熱還流を行っ
た。反応系を冷却し、不溶物を濾別し、濾液を活性炭処
理したのち減圧乾固し、乾固物に炭酸ナトリウムを加え
て系のpHを９〜10となし、析出する粗イミダゾール−４
−アルドキシム0.03モル（3.7ｇ、収率32モル％）をえ
た。このものを熱水にとかし、熱時、活性炭層を通し、
冷時、濾液から析出する結晶を濾取し、水で再結晶して
同定試料とした。Imidazole-4-aldoxime Weakly basic colorless crystals. mP181-183 ° C (water); soluble in water, alcohol and acetone; TLC (silica G, acetone, I 2 color development): Rf0.53-0.65 (The transmittance in% is shown in parentheses; the same applies below.) NMR (d 6 -DMSO): δ 12.28, S, 1H (-NH-); 11.37, S, 1H (= N-OH); 7.6
7, S, 1H (= C-CH =); 7.67, S, 1H (2nd position proton); 7.3
5, S, 1H (proton at 5th position) Mass: m / e 111 (m + ), 84,67,52,39 2-methylimidazole-4-aldoxime Basic colorless crystal. mP163-164 ° C (water); methanol,
And easily soluble in ethanol, soluble in hot water; TLC (silica G, ethanol, I 2 color development): Rf 0.59 to 0.66 NMR (CD 3 OD): δ 7.61, S, 1H (-CH = N-); 7.29, S, 1H (5th position); 2.3
6, S, 3H (methyl) Mass: m / e125 (M +), 108 (M + -OH), 107 (M + -H 2 O), 82,81,66,5
4,41 2-Ethylimidazole-4-aldoxime Weakly basic colorless crystals. mP173 to 175 ° C (water); soluble in water, alcohol and acetone; TLC (silica G, acetone, I 2 color development): Rf 0.41 to 0.52 NMR (CD 3 OD): δ 7.92, S, 1H (anti-type-CH = N-), 7.62, S (5
2nd), 7.31, S (Syn type-CH = N-), 7.08, S (5th), total 2
H; 2.72, q (2nd methylene), 2.68 (2nd methylene) Total 2
H; 1.27, t (2-position methyl), 1.26, t (2-position methyl), total 3H Mass: m / e 139 (M + ), 124, (M + -CH 3 ), 122 (M + -OH) , 95,94,79 2-Undecylimidazole-4-aldoxime Neutral colorless crystal. mP148-154 ° C (ethyl acetate); readily soluble in methanol and ethanol, hot soluble in ethyl acetate, acetone and chloroform, insoluble in water; TLC (silica G, ethanol, I 2 color development): Rf0.76 to 0.86 NMR (CD 3 OD): δ 7.61, S, 1H (-CH = N-); 7.28, S, 1H (5th position); 2.6
9, t, 2H (α-methylene); 1.68, br.m, 2H (β-methylene); 1.27, S, 16H (intermediate methylene group); 0.88, t, 3H (terminal methyl) Mass: m / e 265 (M + ), 248, (M + -OH), 235 (M + -C 2 H 5 ), 222 (M + -
C 3 H 7 ), 208 (M + -C 4 H 9 ), 194,180,166,152,138,125,107,94,
80,55,41 2-Heptadecylimidazole-4-aldoxime Neutral colorless crystal. mP 142-149 ° C (Ethanol) Soluble in DMSO, soluble in methanol and ethanol when hot, insoluble in water; TLC (silica G, ethanol, I 2 coloring): Rf0.68-
0.77 NMR (d 6 -DMSO): δ 7.52, S, 1H (-CH = N-); 7.26, S, 1H (5th position); 2.5
7, t (α-methylene); 1.58, br.S, 2H (β-methylene); 1.22, S, 28H (intermediate methylene group); 0.84, br.t, 3H
(Terminal methyl) Mass: m / e 349 ( M +), 332 (M + -OH), 331 (M + -H 2 O), 320,306,2
92,278,264,250,236,222,208,194,180,163,138,125,12
0,107,80,57,55,42 2-Phenylimidazol-4-aldoxime Light yellow basic crystal. mP184-186 ° C (water); easily soluble in methanol and ascent, soluble in hot water; TLC (silica G,
(Ethanol, BTB color development): Rf 0.65 to 0.75 NMR (CD 3 OD): δ 8.03, S, 0.4H (4th position); 7.82, m, 2.4H (phenyl); 7.43, m, 3.6H (phenyl and -CH = N-); 7.33, S, 0.6 H
(4th) Mass: m / e 187 (M + ), 170 (M + -OH), 144,115,104,77 4-methylimidazole-5-aldoxime Weakly basic colorless crystals. Melts at mP 90-108 ℃, then solidifies and melts again at 147-153. Easily soluble in methanol, ethanol and DMSO, soluble in hot water; TLC (silica G, ethanol, I 2 color development): Rf 0.58 to 0.68 NRM (CD 3 OD): δ 8.03, S, (anti-type-CH = N-), 7.62, S (syn type), total 1H; 7.54, S, 7.36, S, total 1H (2nd); 2.28, S, 3H
(Methyl) Mass: m / e 125 (M + ), 108 (M + -OH), 81 (M + -CH = N-OH), 66,5
4,53,52 2-Ethyl-4-methylimidazole-5-aldoxime Basic colorless crystal. mP205-207 ° C (water); easily soluble in hot water, ethanol and acetone; TLC (silica G, ethanol, I 2 coloring) NMR (CD 3 OD): δ 7.95, and 7.25, S, total 1H (-CH = N-); 2.72; and 2.64,
q, Total 2H (α-methylene); 2.24 and 2.22, S, Total 3H (4th methyl); 1.24, t, 3H (2nd terminal methyl) Mass: m / e153 (M + ), 136 (M + -OH), 109 2,4-Dimethylimidazole-5-aldoxime Basic colorless crystal. mP 48-49 ° C (water); easily soluble in alcohol, acetone and hot water; TLC (silica G, ethanol, I 2 color development): Rf 0.55 to 0.70 NMR (D 2 O): δ 7.98 and 7.32, S, total 1H (-CH = N-); 2.32 and 2.28, S,
Total 3H (methyl 2-position); 2.19 and 2.18, S, Total 3H (methyl 4-position) Mss: m / e 139 (M + ), 122 (M + -OH), 952-phenyl-4-methylimidazole-5 -Aldoxime weakly basic colorless crystals. mP205-207 ° C (CH 3 CN); soluble in methanol and acetone, sparingly soluble in water; TLC (silica G,
Acetone, I 2 color development): Rf 0.86 to 0.75 NMR (CD 3 OD): δ 8.06, s, 1H (-CH = N-); 7.9 to 7.2, m, 5H (phenyl); 2.36, S, 3H (methyl) Mass: m / e201 (M + ), 184 (M + -OH), 170 (M + -NOH), 157,115,10
4,77 Example 1 Imidazole-4-dithiocarboxylic acid 0.1 mol (15 g),
A system consisting of 95% hydroxylamine hydrochloride 0.1 mol (7.6 g), sodium acetic acid 0.1 mol (8.5 g) and acetic acid 40 ml is heated under reflux for 40 minutes, then 95% hydroxylamine hydrochloride 0.05 mol (3.8 g) and acetic acid. 0.05 mol (4.3 g) of sodium was added, and the mixture was further heated and refluxed for 1 hour and 20 minutes. The reaction system is cooled, the insoluble matter is filtered off, the filtrate is treated with activated carbon and then dried under reduced pressure, sodium carbonate is added to the dried matter to adjust the pH of the system to 9 to 10, and crude imidazole-4 is precipitated.
-0.03 mol of aldoxime (3.7 g, yield 32 mol%) was obtained. Dissolve this in hot water and, when hot, pass through the activated carbon layer,
When cold, crystals precipitated from the filtrate were collected by filtration and recrystallized with water to give an identification sample.
実施例２ ２−メチルイミダゾール−４−ジチオカルボン酸0.1モ
ル（16ｇ），塩酸ヒドロキシアミン0.1モル（7.0ｇ），
醋酸ナトリウム0.1モル（7.0）ｇ，醋酸40mlおよび水20
mlの５者から成る系を45分加熱還流したのち、塩酸ヒド
ロキシルアミン0.05モル（3.5ｇ）と醋酸ナトリウム0.0
5モル（4.2ｇ）を追加して、さらに30分間加熱還流を続
けた。Example 2 2-Methylimidazole-4-dithiocarboxylic acid 0.1 mol (16 g), hydroxyamine hydrochloride 0.1 mol (7.0 g),
Sodium acetic acid 0.1 mol (7.0) g, acetic acid 40 ml and water 20
The system consisting of 5 ml was heated under reflux for 45 minutes, then hydroxylamine hydrochloride 0.05 mol (3.5 g) and sodium acetate 0.03
An additional 5 mol (4.2 g) was added and heating at reflux was continued for another 30 minutes.
ついで反応系を冷却し、析出硫黄を濾別し、濾液を減圧
乾固し、乾固物を再び熱水にとかして活性炭層に通し、
かくしてえられる濾液のpHを8.0となし、再び減圧乾固
し、乾固物をエタノール抽出し、抽出液の減圧乾固物を
少量の熱水にとかし、食塩で該水溶液を飽和し、冷時析
出する結晶を濾取し、さらに水で再結晶して粗２−メチ
ルイミダゾール−４−アルドキシム（m.P.88〜115℃）
を0.024モル（3.0ｇ、収率24モル％）をえた。Then, the reaction system was cooled, the precipitated sulfur was filtered off, the filtrate was dried under reduced pressure, the dried solid was again dissolved in hot water and passed through an activated carbon layer,
The pH of the thus-obtained filtrate was adjusted to 8.0, dried again under reduced pressure to dryness, the dried solid was extracted with ethanol, the reduced pressure dried solid of the extract was dissolved in a small amount of hot water, and the aqueous solution was saturated with sodium chloride, and when cold. The precipitated crystals were collected by filtration and recrystallized from water to give crude 2-methylimidazole-4-aldoxime (mP88-115 ° C).
To give 0.024 mol (3.0 g, yield 24 mol%).
実施例３ ２−エチル−４−ジチオカルボン酸0.063モル（10
ｇ），95％塩酸ヒドロキシルアミン0.063モル（4.6
ｇ），醋酸ナトリウム0.063モル（5.2ｇ）および醋酸30
mlの４者からなる系を40分間加熱還流したのち、さらに
95％塩酸ヒドロキシルアミン0.032モル（2.3ｇ）および
醋酸ナトリウム0.032モル（2.6ｇ）を加え１時間20分加
熱還流した。系を冷却後、不溶物を濾別し、濾液を活性
炭層に通したのち、減圧乾固し、乾固物に炭酸ナトリウ
ムを加えて系のpH９〜10とし、析出する粗２−エチルイ
ミダゾール−４−アルドキシム0.032モル（4.0ｇ、収率
49モル％）をえた。このものを熱水にとかし、活性炭処
理したのち、冷時析出する結晶を濾取し、水で再結晶し
て同定試料とした。Example 3 2-ethyl-4-dithiocarboxylic acid 0.063 mol (10
g), 95% hydroxylamine hydrochloride 0.063 mol (4.6
g), sodium acetic acid 0.063 mol (5.2 g) and acetic acid 30
After heating the system consisting of 4 parts of ml to reflux for 40 minutes,
0.032 mol (2.3 g) of 95% hydroxylamine hydrochloride and 0.032 mol (2.6 g) of sodium acetate were added, and the mixture was heated under reflux for 1 hour and 20 minutes. After cooling the system, the insoluble matter was filtered off, the filtrate was passed through an activated carbon layer, dried under reduced pressure, and sodium carbonate was added to the dried matter to adjust the pH of the system to 9 to 10 to precipitate crude 2-ethylimidazole- 4-aldoxime 0.032 mol (4.0 g, yield
49 mol%). This product was dissolved in hot water and treated with activated carbon, and then crystals precipitated in the cold were collected by filtration and recrystallized with water to obtain an identification sample.
実施例４ ２−ウンデシル−４−ジチオカルボン酸0.05モル（15
ｇ），95％塩酸ヒドロキシルアミン0.05モル（3.5
ｇ），醋酸ナトリウム0.05モル（4.1ｇ）および醋酸70m
lの４者からなる系を内温80〜90℃で1.5時間加熱し、つ
いで95％塩酸ヒドロキシルアミン0.026モル（1.8ｇ）お
よび醋酸ナトリウム0.026モル（2.1ｇ）を追加して30分
間加熱をつづけ、さらに両試薬を再び同量追加して30分
間加熱を続けた。ついで系を冷却し、析出硫黄を濾別
し、濾液を活性炭処理し、減圧乾固したのち、乾固物を
熱水にとかし、炭酸ナトリウムを加え系のpHを８とな
し、析出結晶を濾取水洗した。Example 4 2-Undecyl-4-dithiocarboxylic acid 0.05 mol (15
g), 95% hydroxylamine hydrochloride 0.05 mol (3.5
g), Sodium acetic acid 0.05 mol (4.1g) and acetic acid 70m
The system consisting of 4 members was heated at an internal temperature of 80 to 90 ° C for 1.5 hours, and then 0.026 mol (1.8 g) of 95% hydroxylamine hydrochloride and 0.026 mol (2.1 g) of sodium acetate were added and the heating was continued for 30 minutes. Then, the same amount of both reagents was added again and heating was continued for 30 minutes. Then, the system was cooled, the precipitated sulfur was filtered off, the filtrate was treated with activated carbon and dried under reduced pressure, the dried product was dissolved in hot water, sodium carbonate was added to adjust the pH of the system to 8, and the precipitated crystals were filtered. It was washed with water.
該固体をメタノールにとかし、活性炭処理して減圧乾固
し、粗２−ウンデシルイミダゾール−４−アルドキシム
（m.P.138〜146℃）を0.024モル（6.5gr、収率49モル
％）をえた。このものを醋酸エチルで再結晶して同定試
料とした。The solid was dissolved in methanol, treated with activated carbon and dried under reduced pressure to give 0.024 mol (6.5 gr, yield 49 mol%) of crude 2-undecylimidazol-4-aldoxime (mP138-146 ° C). This product was recrystallized with ethyl acetate and used as an identification sample.
実施例５ ２−ヘプタデシル−４−ジチオカルボン酸0.026モル（1
0ｇ），95％塩酸ヒドロキシルアミン0.026モル（1.8
ｇ），醋酸ナトリウム0.026モル（2.1ｇ），醋酸60mlお
よび水10mlよりなる系を１時間加熱還流したのち、95％
塩酸にヒドロキシルアミン0.013モル（0.9ｇ）および醋
酸ナトリウム0.013モル（1.1ｇ）を追加して、さらに30
分間加熱を行ない、再び両試薬を同量追加して、さらに
15分間加熱を続けたのち、反応系を冷却し、析出硫黄を
濾別し、濾液を活性炭処理し、溶媒を減圧留去して黄色
の油状物質をえた。このものに水を加え煮沸攪拌して白
色固体を析出させ、そのものを濾取乾燥して粗２−ヘプ
タデシル−４−アルドキシム（m.P.118〜136℃）を0.02
2モル（7.8ｇ、収率85モル％）をえた。Example 5 2-heptadecyl-4-dithiocarboxylic acid 0.026 mol (1
0 g), 95% hydroxylamine hydrochloride 0.026 mol (1.8
g), sodium acetic acid 0.026 mol (2.1 g), acetic acid 60 ml and water 10 ml.
Add hydroxylamine 0.013mol (0.9g) and sodium acetic acid 0.013mol (1.1g) to hydrochloric acid for another 30
Heat for 1 minute, add the same amount of both reagents again, and
After continuing heating for 15 minutes, the reaction system was cooled, precipitated sulfur was filtered off, the filtrate was treated with activated carbon, and the solvent was distilled off under reduced pressure to obtain a yellow oily substance. Water was added to this substance, and the mixture was boiled with stirring to precipitate a white solid, which was collected by filtration and dried to give crude 2-heptadecyl-4-aldoxime (mP118-136 ° C) at 0.02
2 mol (7.8 g, yield 85 mol%) was obtained.
該粗目的物をエタノールで反復結晶し同定試料をえた。The crude target product was repeatedly crystallized with ethanol to obtain an identification sample.
実施例６ ２−フェニルイミダゾール−４−ジチオカルボン酸0.1
モル（22），95％塩酸ヒドロキシルアミン0.13モル（９
ｇ），醋酸ナトリウム0.13モル（10.7ｇ），醋酸50mlお
よび水10mlの５者からなる系を内温115℃で３時間加熱
還流したのち、系を冷却し、硫黄を濾別し、濾液を活性
炭処理したのち減圧乾固した。この乾固物の水溶液を炭
酸ナトリウムで中和し、析出結晶を濾取し、粗２−フェ
ニルイミダゾール−４−アルドキシムを0.068モル（14.
7ｇ、収率68モル％）をえた。Example 6 2-Phenylimidazole-4-dithiocarboxylic acid 0.1
Mol (22), 95% hydroxylamine hydrochloride 0.13 mol (9
g), sodium acetic acid 0.13 mol (10.7 g), acetic acid 50 ml and water 10 ml, and the system was heated and refluxed at an internal temperature of 115 ° C for 3 hours, then the system was cooled and sulfur was filtered off. After treatment, it was dried under reduced pressure. An aqueous solution of this dry solid was neutralized with sodium carbonate, and the precipitated crystals were collected by filtration to give crude 2-phenylimidazole-4-aldoxime in an amount of 0.068 mol (14.
7 g, yield 68 mol%) was obtained.
上記粗目的物を水で再結晶し同定試料とした。The crude product was recrystallized with water to give an identification sample.
実施例７ ４−メチルイミダゾール−５−ジチオカルボン酸0.07モ
ル（11.2ｇ），95％塩酸ヒドロキシルアミン0.07モル
（4.9ｇ），醋酸ナトリウム0.07モル（5.8ｇ），醋酸60
mlおよび水10mlの５者よりなる系を１時間加熱還流した
のち、塩酸ヒドロキシルアミン0.036モル（2.5ｇ）と醋
酸ナトリウム0.035モル（2.9ｇ）を追加して、さらに30
分間加熱を続けた。系を冷却し、析出硫黄を濾別し、濾
液を減圧乾固し、乾固物を熱水にとかし、活性炭処理し
たのち、炭酸ナトリウムで系のpHを８となし、再び減圧
乾固し、乾固物をエタノール抽出し、抽出液を圧乾固
し、乾固物を少量の水にとかし、該水溶液を食塩で飽和
し、ついで冷却し、析出物を濾取し、水で再結晶して粗
４−メチルイミダゾール−５−アルドキシム（m.P.96〜
100℃）を0.03モル（3.7ｇ、収率42モル）をえた。Example 7 4-Methylimidazole-5-dithiocarboxylic acid 0.07 mol (11.2 g), 95% hydroxylamine hydrochloride 0.07 mol (4.9 g), sodium acetate 0.07 mol (5.8 g), acetic acid 60
After heating and refluxing a system consisting of 5 ml of 10 ml of water and 10 ml of water for 1 hour, 0.036 mol (2.5 g) of hydroxylamine hydrochloride and 0.035 mol (2.9 g) of sodium acetic acid are added, and the mixture is further added to 30 ml.
Continue heating for minutes. The system was cooled, the precipitated sulfur was filtered off, the filtrate was evaporated to dryness under reduced pressure, the dried product was dissolved in hot water, treated with activated carbon, the pH of the system was adjusted to 8 with sodium carbonate, and dried under reduced pressure again. The dry solid was extracted with ethanol, the extract was pressure-dried, the dry solid was dissolved in a small amount of water, the aqueous solution was saturated with sodium chloride, then cooled, and the precipitate was collected by filtration and recrystallized with water. Crude 4-methylimidazole-5-aldoxime (mP96 ~
100 ° C.) gave 0.03 mol (3.7 g, yield 42 mol).
上記粗目的物を水で反復再結晶し同定試料とした。The crude product was repeatedly recrystallized with water to give an identification sample.
実施例８ ２−エチル−４−メチルイミダゾール−５−ジチオカル
ボン酸0.1モル（18.6ｇ），塩酸ヒドロキシルアミン0.1
3モル（9.0ｇ），醋酸ナトリウム0.13モル（10.7ｇ）お
よび85wt％醋酸水溶液60mlの４者からなる系を３時間還
流したのち、系を冷却し、硫黄を濾別し、濾液を活性炭
処理したのち減圧乾固した。この乾固物の水溶液を炭酸
ナトリウムで中和し、再度乾固を行ない、乾固物をエタ
ノール抽出に付し、抽出液を濃縮し、濃縮物に少量の水
を加えたのち濾過を行ない、結晶を濾取し、粗２−エチ
ル−４−メチルイミダゾール−５−アルドキシムを0.05
2モル（9.7ｇ，収率52モル％）をえた。Example 8 2-Ethyl-4-methylimidazole-5-dithiocarboxylic acid 0.1 mol (18.6 g), hydroxylamine hydrochloride 0.1
After refluxing a system consisting of 3 mol (9.0 g), 0.13 mol (10.7 g) of sodium acetate and 60 ml of 85 wt% acetic acid aqueous solution for 3 hours, the system was cooled, sulfur was filtered off, and the filtrate was treated with activated carbon. Then, it was dried under reduced pressure. An aqueous solution of this dry solid was neutralized with sodium carbonate, dried again, the dry solid was subjected to ethanol extraction, the extract was concentrated, and a small amount of water was added to the concentrate, followed by filtration. The crystals were collected by filtration and the crude 2-ethyl-4-methylimidazole-5-aldoxime was added to 0.05
2 mol (9.7 g, yield 52 mol%) was obtained.
実施例９ 2.4−ジメチルイミダゾール−５−ジチオカルボン酸0.1
モル（17.2ｇ），塩酸ヒドロキシルアミン0.13モル（9.
0ｇ），醋酸ナトリウム0.13モル（10.7ｇ）および85wt
％醋酸水溶液55mlの４者からなる系を内温115℃で１時
間30分還流したのち系を冷却し、硫黄を濾別し、濾液を
活性炭処理したのち減圧乾固した。乾固物の水溶液を炭
酸ナトリウムで中和したのち再び乾固した。この乾固物
をエタノール抽出に付し、抽出液を濃縮し、濃縮物に少
量の水を加え、析出結晶を濾取し、粗2,4−ジメチルイ
ミダゾール−５−アルドキシムを0.042モル（7.2ｇ、収
率42モル％）をえた。Example 9 2.4-Dimethylimidazole-5-dithiocarboxylic acid 0.1
Mol (17.2 g), hydroxylamine hydrochloride 0.13 mol (9.
0g), sodium acetic acid 0.13mol (10.7g) and 85wt
The system consisting of four members of 55% aqueous solution of acetic acid was refluxed at an internal temperature of 115 ° C. for 1 hour and 30 minutes, then the system was cooled, sulfur was filtered off, and the filtrate was treated with activated carbon and dried under reduced pressure. The aqueous solution of the dried solid was neutralized with sodium carbonate and then dried again. The dried solid was subjected to ethanol extraction, the extract was concentrated, a small amount of water was added to the concentrate, and the precipitated crystals were collected by filtration to obtain 0.042 mol (7.2 g of crude 2,4-dimethylimidazole-5-aldoxime). , Yield 42 mol%).
該粗目的物を水で反復再結晶して同定試料とした。The crude product was repeatedly recrystallized with water to give an identification sample.
実施例10 ２−フェニル−４−メチルイミダゾール−５−ジチオカ
ルボン酸0.043モル（10.0ｇ），塩酸ヒドロキシルアミ
ン0.043モル（3.1ｇ），醋酸ナトリウム0.043モル（3.5
ｇ）および醋酸30mlの４者からなる系を30分間加熱還流
したのち、さらに塩酸ヒドロキシルアミン0.022モル
（1.6ｇ）および醋酸ナトリウム0.022モル（1.8ｇ）を
加え、１時間加熱還流を行なった。ついで系を熱時濾過
して、濾液を減圧乾固し、乾固物を熱水にとかし、活性
炭処理したのち、炭酸ナトリウムで系のpHを８〜９とな
し、かくして析出する粗２−フェニル−４−メチルイミ
ダゾール−５−アルドキシムを0.026モル（5.15ｇ、収
率60モル％）をえた。Example 10 2-phenyl-4-methylimidazole-5-dithiocarboxylic acid 0.043 mol (10.0 g), hydroxylamine hydrochloride 0.043 mol (3.1 g), sodium acetate 0.043 mol (3.5
g) and 30 ml of acetic acid were heated to reflux for 30 minutes, and then 0.022 mol (1.6 g) of hydroxylamine hydrochloride and 0.022 mol (1.8 g) of sodium acetic acid were added, and the mixture was heated under reflux for 1 hour. Then, the system was filtered while hot, the filtrate was evaporated to dryness under reduced pressure, the dried product was dissolved in hot water, treated with activated carbon, and the pH of the system was adjusted to 8-9 with sodium carbonate. 0.026 mol (5.15 g, yield 60 mol%) of -4-methylimidazole-5-aldoxime was obtained.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 Ｊ．Ｏｒｇ．Ｃｈｅｍ．第41巻第１号 （1976）第19−24頁 Ｂｉｏｏｒｇ．Ｃｈｅｍ．第４巻第３号 （1975）第237−249頁 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References J. Org. Chem. Volume 41 Number 1 (1976) pp. 19-24 Bioorg. Chem. Volume 4 Number 3 (1975) pp. 237-249
Claims (2)
酸ヒドロキシルアミン及び醋酸ナトリウムを加え、醋酸
溶液中で加熱還流することを特徴とする 一般式 〔但し、式中Ｒ2及びＲ4は前記と同じである〕 で示されるイミダゾール−アルドキシム化合物の合成方
法。1. A general formula A hydroxylamine hydrochloride and sodium acetate are added to the imidazole-dithiocarboxylic acid compound represented by, and the mixture is heated under reflux in a solution of acetic acid. [Wherein R 2 and R 4 are the same as defined above], and a method for synthesizing the imidazole-aldoxime compound.
モルに対し、塩酸ヒドロキシルアミン及び醋酸ナトリウ
ムをそれぞれ１．５モル以上用いることを特徴とする特
許請求の範囲(1)に記載の方法。2. An imidazole-dithiocarboxylic acid compound 1
The method according to claim 1, wherein hydroxylamine hydrochloride and sodium acetate are used in an amount of 1.5 mol or more per mol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61014286A JPH0643403B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing imidazole-aldoxime compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61014286A JPH0643403B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing imidazole-aldoxime compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62175469A JPS62175469A (en) | 1987-08-01 |
| JPH0643403B2 true JPH0643403B2 (en) | 1994-06-08 |
Family
ID=11856847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61014286A Expired - Lifetime JPH0643403B2 (en) | 1986-01-25 | 1986-01-25 | Method for synthesizing imidazole-aldoxime compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0643403B2 (en) |
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-
1986
- 1986-01-25 JP JP61014286A patent/JPH0643403B2/en not_active Expired - Lifetime
Non-Patent Citations (2)
| Title |
|---|
| Ｂｉｏｏｒｇ．Ｃｈｅｍ．第４巻第３号（１９７５）第２３７−２４９頁 |
| Ｊ．Ｏｒｇ．Ｃｈｅｍ．第４１巻第１号（１９７６）第１９−２４頁 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62175469A (en) | 1987-08-01 |
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