JPH023784B2 - - Google Patents
Info
- Publication number
- JPH023784B2 JPH023784B2 JP15949881A JP15949881A JPH023784B2 JP H023784 B2 JPH023784 B2 JP H023784B2 JP 15949881 A JP15949881 A JP 15949881A JP 15949881 A JP15949881 A JP 15949881A JP H023784 B2 JPH023784 B2 JP H023784B2
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- dihydro
- imidazole
- acid
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 9
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 241000551547 Dione <red algae> Species 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000002253 acid Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
- 239000013078 crystal Substances 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- -1 amino-3,4-dihydro-2H-imidazole-2,4-diones Chemical class 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- NGNNFDYHJKDHJN-UHFFFAOYSA-N 5-aminoimidazole-2,4-dione Chemical class N=C1NC(=O)NC1=O NGNNFDYHJKDHJN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ABBZJHFBQXYTLU-UHFFFAOYSA-N but-3-enamide Chemical compound NC(=O)CC=C ABBZJHFBQXYTLU-UHFFFAOYSA-N 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 2
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- DWRDBJCTLDOPFZ-UHFFFAOYSA-N imidazole-2,4-dione Chemical class O=C1NC(=O)N=C1 DWRDBJCTLDOPFZ-UHFFFAOYSA-N 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- FOYWCEUVVIHJKD-UHFFFAOYSA-N 2-methyl-5-(1h-pyrazol-5-yl)pyridine Chemical compound C1=NC(C)=CC=C1C1=CC=NN1 FOYWCEUVVIHJKD-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- MSZJEPVVQWJCIF-UHFFFAOYSA-N butylazanide Chemical compound CCCC[NH-] MSZJEPVVQWJCIF-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940047889 isobutyramide Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- XUWVIABDWDTJRZ-UHFFFAOYSA-N propan-2-ylazanide Chemical compound CC(C)[NH-] XUWVIABDWDTJRZ-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
この発明は、５−アミノ−３，４−ジヒドロ−
2H−イミダゾール−２，４−ジオン類の新規な
製造法に関する。
テトラヘドロン・レターズ、2827（1979）には、
２−メチルイミノ）−２−クロロ酢酸エチルとフ
エニル尿素とを、塩化水素の存在下に反応させ
て、５−メチルアミノ−３−フエニル−３，４−
ジヒドロ−2H−イミダゾール−２，４−ジオン
を製造する方法が開示されている。この方法によ
れば、目的生成物は60％と比較的よい収率で得ら
れているが、他の化合物ではどうなるかは開示さ
れていない。
この発明の目的は、５−アミノ−３，４−ジヒ
ドロ−2H−イミダゾール−２，４−ジオン類を
比較的よい収率で得ることのできる新規、かつ一
般的に実施し得る製法を提供することにある。
この発明は、
式
〔式中、R1は炭素数１〜４のアルキル基、炭
素数２〜５のアルケニル基、炭素数５〜７のシク
ロアルキル基、炭素数７〜10のアラルキル基また
は
This invention provides 5-amino-3,4-dihydro-
This invention relates to a new method for producing 2H-imidazole-2,4-diones. Tetrahedron Letters, 2827 (1979),
Ethyl 2-methylimino)-2-chloroacetate and phenyl urea are reacted in the presence of hydrogen chloride to produce 5-methylamino-3-phenyl-3,4-
A method for making dihydro-2H-imidazole-2,4-dione is disclosed. According to this method, the target product is obtained in a relatively good yield of 60%, but it is not disclosed what happens with other compounds. An object of the present invention is to provide a novel and generally practicable process for producing 5-amino-3,4-dihydro-2H-imidazole-2,4-diones in relatively good yields. There is a particular thing. This invention is based on the formula [In the formula, R 1 is an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, an aralkyl group having 7 to 10 carbon atoms, or
【式】（R3は炭素数１〜４のアルキ
ル基またはハロゲン原子を示し、ｎは０，１，２
または３である。）で表わされる基を示し、R2は
炭素数１〜４のアルキル基、炭素数２〜５のアル
ケニル基、炭素数５〜７のシクロアルキル基また
は炭素数７〜10のアラルキル基を示し、R1とR2
とは同じであつても異なつていてもよい。〕で表
わされるアミジンカルボン酸アミド類と、ホスゲ
ンまたはクロロギ酸トリクロロメチルエステルと
を、ピリジンの存在下に反応させることを特徴と
する
式
（式中、R1およびR2は、それぞれ、前記と同
一の意味を有する。）で表わされる５−アミノ−
３，４−ジヒドロ−2H−イミダゾール−２，４
−ジオン類の製造法である。
この発明で得られる５−アミノ−３，４−ジヒ
ドロ−2H−イミダゾール−２，４−ジオン類は、
医薬、農薬、さらにはこれらの中間体として有用
である。
式〔〕で表わされるアミジンカルボン酸アミ
ド類の具体例としては、Ｎ−メチルアミジンカル
ボン酸メチルアミド、Ｎ−エチルアミジンカルボ
ン酸エチルアミド、Ｎ−プロピルアミジンカルボ
ン酸プロピルアミド、Ｎ−ブチルアミジンカルボ
ン酸ブチルアミド、Ｎ−アリルアミジンカルボン
酸アリルアミド、Ｎ−シクロヘキシルアミジンカ
ルボン酸シクロヘキシルアミド、Ｎ−ベンジルア
ミジンカルボン酸ベンジルアミド、Ｎ−フエニル
アミジンカルボン酸シクロヘキシルアミド、Ｎ−
キシリルアミジンカルボン酸アリルアミド、Ｎ−
キシリルアミジンカルボン酸ブチルアミド、Ｎ−
クロロトリルアミジンカルボン酸ブチルアミドな
どが挙げられる。
この発明の方法におけるピリジン存在下での式
〔〕で表わされるアミジンカルボン酸アミド類
とホスゲンまたはクロロギ酸トリクロロメチルエ
ステルとの反応は、溶媒を用いて行なうことが好
ましい。溶媒としては、この発明の方法における
反応に不活性なものであれば、どのようなもので
もよく、たとえば、ベンゼン、トルエン、クロロ
ベンゼン、ジクロロベンゼンなどの芳香族炭化水
素、塩化メチレン、四塩化炭素、塩化エチレンな
どのハワゲン化炭化水素などが挙げられる。な
お、溶媒は反応に先立ち十分に脱水しておくこと
が望ましい。
原料の添加順序については特に制限はないが、
アミジンカルボン酸アミド類およびピリジンを含
む有機溶媒の溶液または懸濁液に、ホスゲンまた
はクロロギ酸トリクロロメチルエステルの有機溶
媒溶液を添加するのが便利である。
アミジンカルボン酸アミド類の使用量は、ホス
ゲン１モル当り0.75〜１モル、クロロギ酸トリク
ロロメチルエステル１モル当り0.35〜0.5モルで
あることが好ましい。
ピリジンの使用量は、ホスゲン１モル当り約２
モル、クロロギ酸トリクロロメチルエステル１モ
ル当り約４モルであることが好ましい。
反応温度は、過度に高いと目的生成物の収率が
低下するので、一般には−20〜40℃の範囲の温度
を採用するのが好ましい。反応時間は通常１〜24
時間である。
目的生成物である５−アミノ−３，４−ジヒド
ロ−2H−イミダゾール−２，４−ジオン類は、
たとえば、つぎの方法によつて単離することがで
きる。
反応生成混合物を水洗して、副生する塩化ピリ
ジニウムを水溶液として除去した後、有機溶媒を
留去し、目的生成物を含む混合物を取得し、この
後、再結晶法などの慣用の精製法によつて、目的
生成物の精製品を単離する。
この発明で得られる式〔〕で表わされる５−
アミノ−３，４−ジヒドロ−2H−イミダゾール
−２，４−ジオン類の具体例としては、３−メチ
ル−５−メチルアミノ−３，４−ジヒドロ−2H
−イミダゾール−２，４−ジオン、３−エチル−
５−エチルアミノ−３，４−ジヒドロ−2H−イ
ミダゾール−２，４−ジオン、３−プロピル−５
−プロピルアミノ−３，４−ジヒドロ−2H−イ
ミダゾール２，４−ジオン、３−ブチル−５−ブ
チルアミノ−３，４−ジヒドロ−2H−イミダゾ
ール−２，４−ジオン、３−アリル−５−アリル
アミノ−３，４−ジヒドロ−2H−イミダゾール
２，４−ジオン、３−シクロヘキシル−５−シク
ロヘキシルアミノ−３，４−ジヒドロ−2H−イ
ミダゾール−２，４−ジオン、３−ベンジル−５
−ベンジルアミノ−３，４−ジヒドロ−2H−イ
ミダゾール−２，４−ジオン、５−アニリノ−３
−シクロヘキシル−３，４−ジヒドロ−2H−イ
ミダゾール−２，４−ジオン、３−アリル−５−
キシリジノ−３，４−ジヒドロ−2H−イミダゾ
ール−２，４−ジオン、３−ブチル−５−キシリ
ジノ−３，４−ジヒドロ−2H−イミダゾール−
２，４−ジオン、３−ブチル−５−クロロトルイ
ジノ−３，４−ジヒドロ−2H−イミダゾール−
２，４−ジオンなどが挙げられる。
つぎに実施例を示す。実施例において、５−ア
ミノ−３，４−ジヒドロ−2H−イミダゾール−
２，４−ジオンの収率は、使用したアミジンカル
ボン酸アミド基準の収率である。
実施例 １
Ｎ−イソプロピルアミジンカルボン酸イソプロ
ピルアミド0.86ｇとピリジン0.96ｇとを含む塩化
エチレン30mlに、氷冷下、クロロギ酸トリクロロ
メチルエステル0.6ｇを含む塩化エチレン10mlを
滴下した後、混合物を室温で撹拌しながら、２時
間反応させた。
反応後、得られた反応生成混合物に、室温で水
30mlを加え、水層と有機層とに分液した。有機層
を無水硫酸ナトリウムで乾燥した後、減圧下に濃
縮して、３−イソプロピル−５−イソプロピルア
ミノ−３，４−ジヒドロ−2H−イミダゾール−
２，４−ジオンの結晶0.85ｇ（収率：86％）を得
た。これをイソプロピルエーテルで再結晶して、
融点147.5〜148.5℃の無色プリズム状結晶を得
た。その元素分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 54.79 7.49 21.34
計算値 54.81 7.67 21.30
（C9H15N3O2として）
実施例 ２
Ｎ−（ｎ−ブチル）アミジンカルボン酸（ｎ−
ブチル）アミド1.99ｇとピリジン1.97ｇとを含む
塩化エチレン20mlに、寒剤（氷−食塩）冷却下、
クロロギ酸トリクロロメチルエステル1.28ｇを含
む塩化エチレン15mlを滴下した後、混合物を室温
で撹拌しながら、４時間反応させた。
反応後、得られた反応生成混合物に、水25mlを
加え、水層と有機層とに分液した。有機層を無水
硫酸ナトリウムで乾燥した後、減圧下に濃縮し
た。残渣の粘着物2.57ｇを、シリカゲル（ワコー
ゲルＣ−200，80ｇ）を詰めたカラム（直径25mm）
に通し、ベンゼンと酢酸エチルとの容量比４：１
の混合溶媒で溶出した。溶媒300mlで溶出した後、
溶媒200mlで溶出して得た溶液を、減圧下に濃縮
して、３−（ｎ−ブチル）−５−（ｎ−ブチルアミ
ノ）−３，４−ジヒドロ−2H−イミダゾール−
２，４−ジオンの結晶1.61ｇ（収率：72％）を得
た。これをイソプロピルエーテルで再結晶して、
融点94.5〜95.5℃の無色結晶を得た。その元素分
析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 58.44 8.29 18.84
計算値 58.64 8.50 18.65
（C11H19N3O2として）
実施例 ３
Ｎ−アリルアミジンカルボン酸アリルアミド
0.84ｇとピリジン1.02ｇを含む塩化エチレン30ml
に、氷冷下、クロロギ酸トリクロロメチルエステ
ル0.64ｇを含む塩化エチレン10mlを滴下した後、
混合物を室温で撹拌しながら、２時間反応させ
た。
反応後、得られた反応生成混合物に、室温で水
30mlを加え、水層と有機層とに分液した。有機層
を無水硫酸ナトリウムで乾燥した後、減圧下に濃
縮した。残渣の粘着物0.83ｇを、シリカゲル（ワ
コーゲルＣ−200，70ｇ）を詰めたカラム（直径
25mm）に通し、ベンゼンと酢酸エチルとの容量比
４：１の混合溶媒で溶離した。溶媒700mlで溶出
した後、溶媒550mlで溶出して得た溶液を、減圧
下に濃縮して、３−アリル−５−アリルアミノ−
３，４−ジヒドロ−2H−イミダゾール−２，４
−ジオンの結晶0.37ｇ（収率：38％）を得た。こ
れをイソプロピルエーテルで再結晶して、融点94
〜95℃の黄色プリズム状結晶を得た。その元素分
析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 55.84 5.76 22.00
計算値 55.95 5.74 21.75
（C9H11N3O2として）
実施例 ４
Ｎ−シクロヘキシルアミジンカルボン酸シクロ
ヘキシルアミド2.51ｇとピリジン1.97ｇを含む塩
化エチレン30mlに、寒剤（氷−食塩）冷却下、ホ
スゲン1.21ｇを含む塩化エチレン20mlを滴下した
後、混合物を室温で撹拌しながら、20時間反応さ
せた。
反応後、得られた反応生成混合物に、水30mlを
加え、過した。液を水層と有機層とに分液し
た。有機層を無水硫酸ナトリウムで乾燥した後、
減圧下に濃縮して、３−シクロヘキシル−５−シ
クロヘキシルアミノ−３，４−ジヒドロ−2H−
イミダゾール−２，４−ジオンの結晶2.59ｇ（収
率：94％）を得た。これをベンゼンで再結晶し
て、融点238〜240℃の無色結晶を得た。その元素
分析値をつぎに示す。
Ｃ Ｈ Ｎ
分析値 62.20 8.36 15.28
計算値 64.96 8.63 15.15
（C15H23N3O2として）
実施例 ５
Ｎ−ベンジルアミジンカルボン酸ベンジルアミ
ド1.9ｇとピリジン1.41ｇを含む塩化エチレン30
mlに、寒剤（氷−食塩）冷却下、ホスゲン0.88ｇ
を含む塩化エチレン10mlを滴下した後、混合物を
室温で撹拌しながら、20時間反応させた。
反応後、得られた反応生成混合物に、室温で水
30mlを加え、水層と有機層とに分液した。有機層
を無水硫酸ナトリウムで乾燥した後、減圧下に濃
縮した。残渣の結晶2.09ｇをエタノール40mlで再
結晶して、３−ベンジル−５−ベンジルアミノ−
３，４−ジヒドロ−2H−イミダゾール−２，４
−ジオンの微黄色微針状結晶0.65ｇ（収率：31
％、融点168〜168℃）を得た。その元素分析値を
つぎに示す。
Ｃ Ｈ Ｎ
分析値 69.93 5.31 14.11
計算値 69.61 5.15 14.33
（C17H15N3O2として）
実施例 ６
Ｎ−（４−クロロ−０−トリルフアミジンカル
ボン酸イソブチルアミド1.34ｇとピリジン0.88ｇ
を含む塩化エチレン20mlに、寒剤（氷−食塩）冷
却下、クロロギ酸トリクロロメチルエステル0.58
ｇを含む塩化エチレン20mlを滴下した後、混合物
を室温で撹拌しながら、15時間反応させた。
反応後、得られた反応生成混合物に、室温で水
40mlを加え、水層と有機層とに分液した。有機層
を無水硫酸ナトリウムで乾燥した後、減圧下に濃
縮した。残渣1.47ｇを、シリカゲル（ワコーゲル
Ｃ−200，100ｇ）を詰めたカラム（直径25mm）に
通し、ベンゼンと酢酸エチルとの容量比９：１の
混合溶媒で溶離した。溶媒120mlで溶出した後、
溶媒165mlで溶出して得た溶液を、減圧下に濃縮
して、５−（４−クロロ−０−トルイジノ）−３−
イソブチル−３，４−ジヒドロ−2H−イミダゾ
ール−２，４−ジオンの結晶0.73ｇ（収率：50
％）を得た。これをシクロヘキサンで再結晶し
て、融点164〜165℃の黄色結晶を得た。その元素
分析値をつぎに示す。
Ｃ Ｈ Ｎ Cl
分析値 57.34 5.57 14.06 11.72
計算値 57.24 5.49 14.30 12.07
（C14H16ClN3O2として）[Formula] (R 3 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, and n is 0, 1, 2
Or 3. ), R2 represents an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, or an aralkyl group having 7 to 10 carbon atoms, R1 and R2
may be the same or different. A formula characterized by reacting an amidinecarboxylic acid amide represented by ] with phosgene or chloroformic acid trichloromethyl ester in the presence of pyridine. (In the formula, R 1 and R 2 each have the same meaning as above.)
3,4-dihydro-2H-imidazole-2,4
- A method for producing diones. The 5-amino-3,4-dihydro-2H-imidazole-2,4-diones obtained in this invention are:
It is useful as medicines, agricultural chemicals, and intermediates thereof. Specific examples of amidinecarboxylic acid amides represented by formula [] include N-methylamidinecarboxylic acid methylamide, N-ethylamidinecarboxylic acid ethylamide, N-propylamidinecarboxylic acid propylamide, N-butylamidinecarboxylic acid butylamide, N-allylamidinecarboxylic acid allylamide, N-cyclohexylamidinecarboxylic acid cyclohexylamide, N-benzylamidinecarboxylic acid benzylamide, N-phenylamidinecarboxylic acid cyclohexylamide, N-
Xylylamidinecarboxylic acid allylamide, N-
Xylylamidinecarboxylic acid butyramide, N-
Examples include chlorotolylamidinecarboxylic acid butyramide. In the method of this invention, the reaction of the amidinecarboxylic acid amide represented by the formula [] with phosgene or trichloromethyl chloroformate in the presence of pyridine is preferably carried out using a solvent. Any solvent may be used as long as it is inert to the reaction in the method of the present invention, such as aromatic hydrocarbons such as benzene, toluene, chlorobenzene, and dichlorobenzene, methylene chloride, carbon tetrachloride, Examples include halogenated hydrocarbons such as ethylene chloride. Note that it is desirable that the solvent be sufficiently dehydrated prior to the reaction. There are no particular restrictions on the order of addition of raw materials, but
It is convenient to add a solution of phosgene or chloroformic acid trichloromethyl ester in an organic solvent to a solution or suspension of the amidinecarboxylic acid amide and pyridine in an organic solvent. The amount of amidinecarboxylic acid amide used is preferably 0.75 to 1 mol per mol of phosgene and 0.35 to 0.5 mol per mol of trichloromethyl chloroformate. The amount of pyridine used is approximately 2 per mole of phosgene.
mole, preferably about 4 moles per mole of chloroformic acid trichloromethyl ester. If the reaction temperature is too high, the yield of the desired product will decrease, so it is generally preferable to employ a temperature in the range of -20 to 40°C. Reaction time is usually 1-24
It's time. The target product, 5-amino-3,4-dihydro-2H-imidazole-2,4-diones, is
For example, it can be isolated by the following method. After washing the reaction product mixture with water to remove by-product pyridinium chloride as an aqueous solution, the organic solvent is distilled off to obtain a mixture containing the desired product, which is then subjected to a conventional purification method such as recrystallization. Thus, the purified product of interest is isolated. 5- expressed by the formula [] obtained by this invention
Specific examples of amino-3,4-dihydro-2H-imidazole-2,4-diones include 3-methyl-5-methylamino-3,4-dihydro-2H
-imidazole-2,4-dione, 3-ethyl-
5-ethylamino-3,4-dihydro-2H-imidazole-2,4-dione, 3-propyl-5
-Propylamino-3,4-dihydro-2H-imidazole2,4-dione, 3-butyl-5-butylamino-3,4-dihydro-2H-imidazole-2,4-dione, 3-allyl-5- Allylamino-3,4-dihydro-2H-imidazole2,4-dione, 3-cyclohexyl-5-cyclohexylamino-3,4-dihydro-2H-imidazole-2,4-dione, 3-benzyl-5
-benzylamino-3,4-dihydro-2H-imidazole-2,4-dione, 5-anilino-3
-cyclohexyl-3,4-dihydro-2H-imidazole-2,4-dione, 3-allyl-5-
Xylidino-3,4-dihydro-2H-imidazole-2,4-dione, 3-butyl-5-xylidino-3,4-dihydro-2H-imidazole-
2,4-dione, 3-butyl-5-chlorotoluidino-3,4-dihydro-2H-imidazole-
Examples include 2,4-dione. Next, examples will be shown. In the examples, 5-amino-3,4-dihydro-2H-imidazole-
The yield of 2,4-dione is based on the amidinecarboxylic acid amide used. Example 1 To 30 ml of ethylene chloride containing 0.86 g of N-isopropylamidinecarboxylic acid isopropylamide and 0.96 g of pyridine, 10 ml of ethylene chloride containing 0.6 g of chloroformic acid trichloromethyl ester was added dropwise under ice cooling, and the mixture was stirred at room temperature. The reaction was allowed to proceed for 2 hours while stirring. After the reaction, the resulting reaction product mixture was added with water at room temperature.
30 ml was added, and the layers were separated into an aqueous layer and an organic layer. After drying the organic layer over anhydrous sodium sulfate, it was concentrated under reduced pressure to give 3-isopropyl-5-isopropylamino-3,4-dihydro-2H-imidazole-
0.85 g (yield: 86%) of 2,4-dione crystals were obtained. This was recrystallized from isopropyl ether,
Colorless prismatic crystals with a melting point of 147.5-148.5°C were obtained. The elemental analysis values are shown below. C H N Analytical value 54.79 7.49 21.34 Calculated value 54.81 7.67 21.30 (as C 9 H 15 N 3 O 2 ) Example 2 N-(n-butyl)amidinecarboxylic acid (n-
20 ml of ethylene chloride containing 1.99 g of (butyl) amide and 1.97 g of pyridine, under cooling with a cryogen (ice-salt),
After dropping 15 ml of ethylene chloride containing 1.28 g of chloroformic acid trichloromethyl ester, the mixture was reacted for 4 hours with stirring at room temperature. After the reaction, 25 ml of water was added to the resulting reaction product mixture to separate it into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. A column (diameter 25 mm) packed with 2.57 g of sticky residue and silica gel (Wako Gel C-200, 80 g)
of benzene and ethyl acetate in a volume ratio of 4:1.
It was eluted with a mixed solvent of After elution with 300ml of solvent,
The solution obtained by elution with 200 ml of solvent was concentrated under reduced pressure to give 3-(n-butyl)-5-(n-butylamino)-3,4-dihydro-2H-imidazole-
1.61 g (yield: 72%) of 2,4-dione crystals were obtained. This was recrystallized from isopropyl ether,
Colorless crystals with a melting point of 94.5-95.5°C were obtained. The elemental analysis values are shown below. C H N Analytical value 58.44 8.29 18.84 Calculated value 58.64 8.50 18.65 (as C 11 H 19 N 3 O 2 ) Example 3 N-allylamidinecarboxylic acid allylamide
30 ml of ethylene chloride containing 0.84 g and 1.02 g of pyridine
After dropping 10 ml of ethylene chloride containing 0.64 g of chloroformic acid trichloromethyl ester into the solution under ice cooling,
The mixture was allowed to react for 2 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was added with water at room temperature.
30 ml was added, and the layers were separated into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 0.83 g of sticky residue was placed in a column (diameter
25 mm) and eluted with a mixed solvent of benzene and ethyl acetate in a volume ratio of 4:1. After elution with 700 ml of solvent, the solution obtained by elution with 550 ml of solvent was concentrated under reduced pressure to obtain 3-allyl-5-allylamino-
3,4-dihydro-2H-imidazole-2,4
-0.37 g (yield: 38%) of dione crystals were obtained. This was recrystallized from isopropyl ether and had a melting point of 94.
Yellow prismatic crystals at ~95°C were obtained. The elemental analysis values are shown below. C H N Analytical value 55.84 5.76 22.00 Calculated value 55.95 5.74 21.75 (as C 9 H 11 N 3 O 2 ) Example 4 A cryogen ( After cooling (ice-salt), 20 ml of ethylene chloride containing 1.21 g of phosgene was added dropwise, and the mixture was reacted for 20 hours with stirring at room temperature. After the reaction, 30 ml of water was added to the resulting reaction product mixture and filtered. The liquid was separated into an aqueous layer and an organic layer. After drying the organic layer with anhydrous sodium sulfate,
Concentrate under reduced pressure to give 3-cyclohexyl-5-cyclohexylamino-3,4-dihydro-2H-
2.59 g (yield: 94%) of imidazole-2,4-dione crystals were obtained. This was recrystallized from benzene to obtain colorless crystals with a melting point of 238-240°C. The elemental analysis values are shown below. C H N Analytical value 62.20 8.36 15.28 Calculated value 64.96 8.63 15.15 (as C 15 H 23 N 3 O 2 ) Example 5 Ethylene chloride 30 containing 1.9 g of N-benzylamidinecarboxylic acid benzylamide and 1.41 g of pyridine
ml, 0.88 g of phosgene under cooling with cryogen (ice-salt)
After dropping 10 ml of ethylene chloride containing 100 ml of ethylene chloride, the mixture was reacted for 20 hours with stirring at room temperature. After the reaction, the resulting reaction product mixture was added with water at room temperature.
30 ml was added, and the layers were separated into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 2.09 g of the residual crystals were recrystallized from 40 ml of ethanol to give 3-benzyl-5-benzylamino-
3,4-dihydro-2H-imidazole-2,4
- 0.65 g of pale yellow microacicular crystals of dione (yield: 31
%, melting point 168-168°C). The elemental analysis values are shown below. C H N Analytical value 69.93 5.31 14.11 Calculated value 69.61 5.15 14.33 (as C 17 H 15 N 3 O 2 ) Example 6 N-(4-chloro-0-tolylfamidinecarboxylic acid isobutyramide 1.34 g and pyridine 0.88 g
To 20 ml of ethylene chloride containing
After dropping 20 ml of ethylene chloride containing g, the mixture was reacted at room temperature for 15 hours with stirring. After the reaction, the resulting reaction product mixture was added with water at room temperature.
40 ml was added to separate into an aqueous layer and an organic layer. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. 1.47 g of the residue was passed through a column (diameter 25 mm) packed with silica gel (Wako Gel C-200, 100 g) and eluted with a mixed solvent of benzene and ethyl acetate in a volume ratio of 9:1. After elution with 120ml of solvent,
The solution obtained by elution with 165 ml of solvent was concentrated under reduced pressure to give 5-(4-chloro-0-toluidino)-3-
0.73 g of crystals of isobutyl-3,4-dihydro-2H-imidazole-2,4-dione (yield: 50
%) was obtained. This was recrystallized from cyclohexane to obtain yellow crystals with a melting point of 164-165°C. The elemental analysis values are shown below. C H N Cl Analytical value 57.34 5.57 14.06 11.72 Calculated value 57.24 5.49 14.30 12.07 (as C 14 H 16 ClN 3 O 2 )
Claims (1)
素数２〜５のアルケニル基、炭素数５〜７のシク
ロアルキル基、炭素数７〜10のアラルキル基また
は【式】（R3は炭素数１〜４のアルキ ル基またはハロゲン原子を示し、ｎは０，１，２
または３である。）で表わされる基を示し、R2は
炭素数１〜４のアルキル基、炭素数２〜５のアル
ケニル基、炭素数５〜７のシクロアルキル基また
は炭素数７〜10のアラルキル基を示し、R1とR2
とは同じであつても異なつていてもよい。〕で表
わされるアミジンカルボン酸アミド類と、ホスゲ
ンまたはクロロギ酸トリクロロメチルエステルと
を、ピリジンの存在下に反応させることを特徴と
する。 式 （式中、R1およびR2は、それぞれ、前記と同
一の意味を有する。）で表わされる５−アミノ−
３，４−ジヒドロ−2H−イミダゾール−２，４
−ジオン類の製造法。[Claims] 1 formula [In the formula, R 1 is an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, an aralkyl group having 7 to 10 carbon atoms, or [Formula] (R 3 represents an alkyl group having 1 to 4 carbon atoms or a halogen atom, and n is 0, 1, 2
Or 3. ), R2 represents an alkyl group having 1 to 4 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, a cycloalkyl group having 5 to 7 carbon atoms, or an aralkyl group having 7 to 10 carbon atoms, R1 and R2
may be the same or different. It is characterized by reacting the amidinecarboxylic acid amide represented by ] with phosgene or chloroformic acid trichloromethyl ester in the presence of pyridine. formula (In the formula, R 1 and R 2 each have the same meaning as above.)
3,4-dihydro-2H-imidazole-2,4
-Production method of diones.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15949881A JPS5862165A (en) | 1981-10-08 | 1981-10-08 | Preparation of 5-amino-3,4-dihydro-2h-imidazole-2,4-diones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15949881A JPS5862165A (en) | 1981-10-08 | 1981-10-08 | Preparation of 5-amino-3,4-dihydro-2h-imidazole-2,4-diones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5862165A JPS5862165A (en) | 1983-04-13 |
| JPH023784B2 true JPH023784B2 (en) | 1990-01-24 |
Family
ID=15695077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15949881A Granted JPS5862165A (en) | 1981-10-08 | 1981-10-08 | Preparation of 5-amino-3,4-dihydro-2h-imidazole-2,4-diones |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5862165A (en) |
-
1981
- 1981-10-08 JP JP15949881A patent/JPS5862165A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5862165A (en) | 1983-04-13 |
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