JPH01254668A - Electrochemical production of barbituric acid derivative - Google Patents
Electrochemical production of barbituric acid derivativeInfo
- Publication number
- JPH01254668A JPH01254668A JP7809088A JP7809088A JPH01254668A JP H01254668 A JPH01254668 A JP H01254668A JP 7809088 A JP7809088 A JP 7809088A JP 7809088 A JP7809088 A JP 7809088A JP H01254668 A JPH01254668 A JP H01254668A
- Authority
- JP
- Japan
- Prior art keywords
- urea
- derivative
- reaction
- raw material
- malonic 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title description 4
- DNZPLHRZXUJATK-UHFFFAOYSA-N 2-sulfanylidene-5-[[5-[2-(trifluoromethyl)phenyl]furan-2-yl]methyl]-1,3-diazinane-4,6-dione Chemical compound FC(F)(F)C1=CC=CC=C1C(O1)=CC=C1CC1C(=O)NC(=S)NC1=O DNZPLHRZXUJATK-UHFFFAOYSA-N 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 239000004202 carbamide Substances 0.000 claims abstract description 15
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 14
- -1 malonic acid ester Chemical class 0.000 claims abstract description 14
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 150000003672 ureas Chemical class 0.000 claims description 5
- 150000007656 barbituric acids Chemical class 0.000 claims description 4
- 238000002848 electrochemical method Methods 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 18
- 239000002994 raw material Substances 0.000 abstract description 9
- 238000005868 electrolysis reaction Methods 0.000 abstract description 7
- 150000002148 esters Chemical class 0.000 abstract description 7
- 239000003115 supporting electrolyte Substances 0.000 abstract description 5
- WGHUNMFFLAMBJD-UHFFFAOYSA-M tetraethylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC[N+](CC)(CC)CC WGHUNMFFLAMBJD-UHFFFAOYSA-M 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 3
- 230000005611 electricity Effects 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 230000000147 hypnotic effect Effects 0.000 abstract description 2
- 230000001624 sedative effect Effects 0.000 abstract description 2
- UZPGPVQCDJXSNM-UHFFFAOYSA-M tetrabutylazanium;iodate Chemical compound [O-]I(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC UZPGPVQCDJXSNM-UHFFFAOYSA-M 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 239000003054 catalyst Substances 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- KRZLPCLVDVLDJZ-UHFFFAOYSA-N 2-(3-phenylpropyl)propanedioic acid Chemical compound OC(=O)C(C(O)=O)CCCC1=CC=CC=C1 KRZLPCLVDVLDJZ-UHFFFAOYSA-N 0.000 description 2
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- ZKBBUZRGPULIRN-UHFFFAOYSA-N diethyl 2,2-diethylpropanedioate Chemical compound CCOC(=O)C(CC)(CC)C(=O)OCC ZKBBUZRGPULIRN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- OTAJXSDTVOGIBR-UHFFFAOYSA-N 2-ethyl-2-pentan-2-ylpropanedioic acid Chemical compound CCCC(C)C(CC)(C(O)=O)C(O)=O OTAJXSDTVOGIBR-UHFFFAOYSA-N 0.000 description 1
- KDEAZJJSARLKAO-UHFFFAOYSA-N 2-ethyl-2-phenylpropanedioic acid Chemical compound CCC(C(O)=O)(C(O)=O)C1=CC=CC=C1 KDEAZJJSARLKAO-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- GZDFOOAFMQSYOV-UHFFFAOYSA-N 3-(cyclohexylmethyl)-1,8-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)C=2NC(C)=NC=2N1CC1CCCCC1 GZDFOOAFMQSYOV-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 101100434906 Mus musculus Angptl8 gene Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はバルビッール酸誘導体の電気化学的合成法に関
する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for electrochemical synthesis of barbylic acid derivatives.
バルビッール酸誘導体は周知のように、マロン酸と尿素
の縮合により得られるバルビッール酸の誘導体であって
、特にその５位の側鎖が種々の基で置換されたものは催
眠、鎮静等の作用があり、医薬として広く利用されてい
る。As is well known, barbituric acid derivatives are derivatives of barbituric acid obtained by condensation of malonic acid and urea, and those in which the 5-position side chain is substituted with various groups have hypnotic and sedative effects. It is widely used as a medicine.
従・来、このバルビッール酸誘導体の製造法としては、
アルキルマロン酸エステルと尿素を無水エタノール中、
ナトリウムエトキシドの存在下で煮沸して製造したり（
Ｅ、Ｆｉｓｃｈｅｒ ａｎｄ Ａ、Ｄｉｌｔｈｅｙ。Traditionally, the method for producing this barbylic acid derivative is as follows:
Alkyl malonic acid ester and urea in absolute ethanol,
Produced by boiling in the presence of sodium ethoxide (
E., Fischer and A., Dilthey.
」吸９．競５，３３４ （１９０４）参照〕、液安中ナ
トリウムアルコラード、水酸化ナトリウム等を用いて室
温下で反応させ製造していた〔下、若松、エル。” Suction 9. 5, 334 (1904)] and was produced by reacting at room temperature using sodium alcolade in liquid ammonium, sodium hydroxide, etc. [see, Wakamatsu, L. et al.
興、１１４１ （１９５７）参照〕。See Ko, 1141 (1957)].
しかし、それらの方法は前者の場合には煮沸下で、又後
者の場合でも液安中というそれぞれ厳しい反応条件下で
行わなければならないという問題点があった。However, these methods have the problem that the reaction must be carried out under severe reaction conditions, such as under boiling in the former case, and in liquid ammonium in the latter case.
本発明は室温ドという穏やかな反応条件下に、収率よく
バルビッール酸誘導体を製造する新規な方法を提供づる
ことを目的としてなされたものである。The object of the present invention is to provide a new method for producing barbylic acid derivatives in good yield under mild reaction conditions at room temperature.
（課題を解決するための手段）
本発明者らは上記目的を達成するためＵ１究を重ねた結
果、各種マロン酸エステルと尿素を電解槽の陰極室に於
いて電極反応させることにより、室温で収率よくバルビ
ッール酸誘導体が得られることを見出し、本発明を完成
した。(Means for Solving the Problems) As a result of repeated research in order to achieve the above object, the inventors of the present invention discovered that various malonic acid esters and urea were caused to react with each other at room temperature in the cathode chamber of an electrolytic cell. It was discovered that barbylic acid derivatives can be obtained in good yield, and the present invention was completed.
すなわら、本発明はマロン酸エステル誘導体に尿素又は
尿素誘導体を加え、電解反応せしめることを特徴とする
バルビッールＭ誘導体の電気化学的！４造法を提供する
ものである。That is, the present invention is an electrochemical method of Barbyl M derivatives, which is characterized by adding urea or a urea derivative to a malonic acid ester derivative and causing an electrolytic reaction. It provides four construction methods.
以下本発明の詳細な説明する。The present invention will be explained in detail below.
本発明のパルどツール酸誘導体の電気化学的合成法は次
の反応式に従って進行する。The electrochemical synthesis method for paldoturic acid derivatives of the present invention proceeds according to the following reaction formula.
Ｉ＜４
式中Ｒ，，Ｒ２は直鎖又は分岐鎖アルキル基、アリル基
、フェニル基、ベンジル基、シクロへキセニル基、１−
メチル−１−ブテニル基等よりなる群から選ばれた基を
表わし、Ｒ３は低級アルキル基、例えばメチル、エチル
、プロピル基等、又は７リール基、例えばフェニル、ナ
フチル基等を表わし、Ｒ４は水素又は直鎖低級アルキル
基もしくはフェニル基を表わす。I<4 In the formula, R,, R2 is a linear or branched alkyl group, allyl group, phenyl group, benzyl group, cyclohexenyl group, 1-
Represents a group selected from the group consisting of methyl-1-butenyl, etc., R3 represents a lower alkyl group, such as methyl, ethyl, propyl, etc., or a 7-aryl group, such as phenyl, naphthyl, etc., and R4 represents hydrogen. Or it represents a linear lower alkyl group or a phenyl group.
本発明で用いられる原料のマロン酸エステル誘導体とし
ては上記反応式で示したように、直鎖もしくは分岐鎖ア
ルキル基、アリール基、フェニル基、ベンジル基、シク
ロへキセニル基、１−メチル−１−ブテニル基等の置換
基を有するマロン酸エステル誘導体が用いられる。As shown in the reaction formula above, the raw malonic acid ester derivatives used in the present invention include linear or branched alkyl groups, aryl groups, phenyl groups, benzyl groups, cyclohexenyl groups, 1-methyl-1- A malonic acid ester derivative having a substituent such as a butenyl group is used.
なお、直鎖アルキル基としては、例えばエチル、プロピ
ル、ブチル基等が好ましく、分岐鎖アルキル基としては
１−メチルブチル基、１−メチルブチル基、イソブチル
基、エチル−１−メチルブチル基、イソペンチル基等が
好ましい。In addition, as the straight chain alkyl group, for example, ethyl, propyl, butyl group, etc. are preferable, and as the branched chain alkyl group, 1-methylbutyl group, 1-methylbutyl group, isobutyl group, ethyl-1-methylbutyl group, isopentyl group, etc. preferable.
又、該マロン酸ニスデル誘導体のエステルを構成する低
級アルキル基（Ｒ３）は特にエチル基又はフェニル基等
が好ましい。Further, the lower alkyl group (R3) constituting the ester of the Nisder malonate derivative is particularly preferably an ethyl group or a phenyl group.
本発明のもう一方の原料である尿素類は尿素それ自体の
他、アルキル尿素、フェニル尿素等の誘導体が用いられ
る。As the urea which is another raw material of the present invention, in addition to urea itself, derivatives such as alkyl urea and phenyl urea are used.
本発明の製造方法は原料のマロン酸エステル誘導体と尿
素又は尿素誘導体を有機溶媒及び支持電解質とともに電
解槽の陰極室に入れ、通電することにより行われる。The production method of the present invention is carried out by placing the malonic acid ester derivative and urea or urea derivative as raw materials in a cathode chamber of an electrolytic cell together with an organic solvent and a supporting electrolyte, and applying electricity.
本発明で用いられる有機溶媒は原料のマロン酸エステル
誘導体、尿素又は尿素誘導体、及び支持電解質を溶解す
る非プロトン性の極性溶媒なら、いずれも使用できるが
、特にジメチルホルムアミド（ＤＭＦ＞が好ましい。The organic solvent used in the present invention can be any aprotic polar solvent that dissolves the raw material malonic acid ester derivative, urea or urea derivative, and supporting electrolyte, but dimethylformamide (DMF) is particularly preferred.
又、支持電解質としては過塩素酸テトラエチルアンモニ
ウム（ＴＥＡＰ） 、沃素酸テトラブチルアンモニウム
（ＴＢＡＴ）等を用いることができる。Further, as the supporting electrolyte, tetraethylammonium perchlorate (TEAP), tetrabutylammonium iodate (TBAT), etc. can be used.
反応温度は１８〜２８℃程度のいわゆる室温でよく、こ
れが本発明の特徴の１つになっているが、必要により、
他の適当な温度を選ぶこともできる。The reaction temperature may be about 18 to 28°C, so-called room temperature, which is one of the characteristics of the present invention, but if necessary,
Other suitable temperatures can also be selected.
原料のマロン酸エステル誘導体と尿素又は尿素誘導体の
量比は臨界的ではないが通常等モル、好ましくは２倍モ
ル以上で行うのがよい。Although the quantitative ratio of the raw material malonic acid ester derivative to urea or urea derivative is not critical, it is usually equimolar, preferably at least twice the molar amount.
本発明の電解反応条例としては３〜１５ｍＡ／Ｃｄの定
電流密度電解で原料エステルに対して２〜ＩＯＦ／ｍｏ
ｌの通電量、好ましくは、５〜１０ｍＡ／ＣＩｉの定電
流密度電解で、通電量３〜５Ｆ／ｍｏｌで行なわれる。The electrolytic reaction regulations of the present invention are 2 to IOF/mo to the raw material ester by constant current density electrolysis of 3 to 15 mA/Cd.
The electrolysis is carried out at a constant current density electrolysis of 1, preferably 5 to 10 mA/CIi, and a current of 3 to 5 F/mol.
本発明で使用する電解槽は従来から用いられている通常
の電解槽、例えばガラスフィルターを隔膜とするト１型
電解セル或いは円筒型電解セル等を設けた電解槽を用い
ることができる。The electrolytic cell used in the present invention may be an ordinary electrolytic cell conventionally used, for example, an electrolytic cell equipped with a type 1 electrolytic cell or a cylindrical electrolytic cell using a glass filter as a diaphragm.
又、電極も特に制限はないが、両極とも白金電極・ｂし
くは炭素電極等が好適に使用される。Further, the electrodes are not particularly limited, but platinum electrodes, carbon electrodes, etc. are preferably used for both electrodes.
反応終了後、目的物であるパルどツールｒｉｆｌ誘導体
は、通常の操作、例えば溶媒除去し、再結晶、クロマト
グラフィー等の組合わせにより分溜１精製することがで
きる。After completion of the reaction, the target product, the Paldotool rifl derivative, can be purified by fractional distillation by a combination of conventional operations such as solvent removal, recrystallization, chromatography, and the like.
以下実施例で本発明を具体的に説明する。 The present invention will be specifically explained below with reference to Examples.
実施例１〜５
電解槽はＧ−３ガラスフイルター隔壁で陽極室と陰極室
を仕切り、磁気攪拌装置を設け、陽極、陰極ともに白金
電極を用い、外側から２３±２℃の水で恒温にしたもの
を用いた。これに陰極液としてジエチルマロン酸ジエチ
ル１００ｍｇ（０，５ｍｍｏｌ）、及び尿素３０ｍｇ
（０，５ｍ ｍｏｌ ）もしくは８０ｍｒｉ （１ｍ
ｍｏｌ ）を０．１旧丁ＥＡＰのＤＭＦ溶液１０−に溶
かして入れ、陽極液として０．１８−ＴＥＡＰのＤＭＦ
溶液１０ｒｒｄｌを入れて５１ＩＩＡ／ｃｄの定電流密
度電解をおこなった。通電量はエステルに対して５Ｆ／
ｍｏｌ とした。反応終了後、両極液を合わせて中和し
、溶媒は５０°Ｃで減圧留去した。残留物に酢酸エチル
１０ｄを加えるとＴ［＾Ｐか析出するので、これをろ別
し、ろ液は溶媒を減圧留去した。ここに得られた反応生
成物につきクロロホルム−メタノール（８０： １ ）
を展開溶媒としたシリカゲルカラムクロマトグラフィー
により分離精製し、原料エステル１３ｍｇ（１３％）、
バルビタール５８ｍ９（７１％）を得た（実施例１）。Examples 1 to 5 The electrolytic cell was divided into an anode chamber and a cathode chamber by a G-3 glass filter partition wall, equipped with a magnetic stirring device, used platinum electrodes for both the anode and cathode, and kept at a constant temperature with water at 23±2°C from the outside. I used something. To this, 100 mg (0.5 mmol) of diethyl diethylmalonate and 30 mg of urea were added as catholyte.
(0.5m mol) or 80mri (1m
mol ) in 0.1 TEAP DMF solution 10-, and 0.18-TEAP DMF as anolyte.
10 rrdl of solution was added and constant current density electrolysis of 51 IIA/cd was performed. The amount of current is 5F/ for ester.
It was set as mol. After the reaction was completed, both polar solutions were combined and neutralized, and the solvent was distilled off under reduced pressure at 50°C. When 10 d of ethyl acetate was added to the residue, T[^P was precipitated, which was filtered off, and the solvent of the filtrate was distilled off under reduced pressure. Chloroform-methanol (80:1) for the reaction product obtained here.
Separated and purified by silica gel column chromatography using as a developing solvent, 13 mg (13%) of raw material ester,
58m9 (71%) of barbital was obtained (Example 1).
なお、比較のため上記反応液を１３０℃で３Ｒ間加熱し
てみたが、反応は進行しなかった。For comparison, the above reaction solution was heated at 130° C. for 3R, but the reaction did not proceed.
次にジアリルマロンＭ（実施例２）、エチルフェニルマ
ロン酸（実施例３）、エチル−１−メチルブチルマロン
酸（実施例４）、ベンジルエチルマロン酸（実施例５）
の各ジエチルエステルと尿素についても同様にして電解
反応を行い、それぞれ相当するバルビッール酸誘導体を
得た。結果は表１に示した。なお、得られたバルビッー
ル酸誘導体は夫々常法により化学的に合成した標品と混
融試験、ＩＲ，ＴＬＣにより同定し、確認した。Next, diallylmalon M (Example 2), ethyl phenylmalonic acid (Example 3), ethyl-1-methylbutylmalonic acid (Example 4), benzylethylmalonic acid (Example 5)
The electrolytic reaction was carried out in the same manner for each diethyl ester and urea, and the corresponding barbylic acid derivatives were obtained. The results are shown in Table 1. The obtained barbituric acid derivatives were identified and confirmed by mixing test, IR, and TLC with standard products chemically synthesized by conventional methods.
（以下余白〉
実施例６
実施例１と同じ電解槽を用い、ジエチルマロン酸ジエチ
ル１００ｍｙ （０，５ｍ ｎｏｔ ） 、フェニル尿
素６５ｒｒ１ｇ （０，５ｍ １ＩＩｏｔ ）を０．１
８−ＴＥＡＰのＤＨＦ溶液１０ｄに溶かして陰極とし、
陽極液としては、０．１８−ＴＥＡＰのＤＭＦ溶液１０
７！を用い、５ｍＡ／ｃｄの定電流密度電解で、通電量
をエステルに対して５Ｆ／ｍｏｌとして電解反応を行な
った。なお、比較のためアセトニトリルを溶媒として行
ってみたが収率は３％と低く副産物ら多かった。反応終
了後、両極液を合わせて中和し、溶媒は５０℃で減圧留
去した。残留物にクロロホルム１０ｍを加え、析出した
ＴＥＡＰろ別し、ろ液は溶媒を減圧留去した後、クロロ
ホルムベキ４ノン（１５： １ ）を展開溶媒としたシ
リカゲルカラムクロマトグラフィーに付し、さらにクロ
ロホルム−シクロへキリン（２０：１）を展開溶媒とす
る中圧液体クロマトグラフィーにより分離精製した。(Left below) Example 6 Using the same electrolytic cell as in Example 1, 100my (0.5m not ) of diethyl diethylmalonate and 65rr1g (0.5m 1IIot ) of phenyl urea were added at 0.1
8-TEAP was dissolved in 10 d of DHF solution to serve as a cathode,
As the anolyte, a solution of 0.18-TEAP in DMF 10
7! An electrolytic reaction was carried out using constant current density electrolysis at 5 mA/cd, with the amount of current applied to the ester being 5 F/mol. For comparison, acetonitrile was used as a solvent, but the yield was as low as 3% and there were many by-products. After the reaction was completed, both polar solutions were combined and neutralized, and the solvent was distilled off under reduced pressure at 50°C. 10 ml of chloroform was added to the residue, and the precipitated TEAP was filtered off. After distilling off the solvent under reduced pressure, the filtrate was subjected to silica gel column chromatography using chloroform bequinone (15:1) as a developing solvent, and further chloroform - Separation and purification was performed by medium pressure liquid chromatography using cyclohexylline (20:1) as a developing solvent.
結果は表２に示プ。The results are shown in Table 2.
ここで得られたバルビッール酸誘導体はＨｅ ｌ ｇｅ
Ａｓｐｅｌｕｎｄらの方法（１１，Ａｓｐｅｌｕｎｄ、
０．８ａｃｋｍａｎ、 Ａｃｔａ。The barbylic acid derivative obtained here is
Aspelund et al.'s method (11, Aspelund,
0.8ackman, Acta.
Ａｃａｄ、Ａｂｏｅｎｓｉｓ、 ）ｌａｔｈ、 ｅｔ
Ｐｈｙｓ、 、 １４．１９（１９４４）参照〕により
合成した標品と混融試験、ＴＬＣ，ＩＲにより同定した
。Acad, Aboensis, ) lath, et
Phys, 14.19 (1944)] and was identified by mixing test, TLC, and IR.
（以下余白）
〔発明の効果〕
本発明の最大の効果は医薬品として重要なバルビッール
酸誘導体を新規電解合成法により、室温下という温和な
反応条件下で収率よく製造することを可能にした点にあ
る。(The following is a blank space) [Effects of the invention] The greatest effect of the present invention is that it has made it possible to produce barbylic acid derivatives, which are important as pharmaceuticals, in good yields under mild reaction conditions at room temperature using a new electrolytic synthesis method. It is in.
Claims (1)
え、電解反応せしめることを特徴とするバルビツール酸
誘導体の電気化学的製造法。1. An electrochemical method for producing barbituric acid derivatives, which comprises adding urea or a urea derivative to a malonic acid ester derivative and causing an electrolytic reaction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7809088A JPH0730045B2 (en) | 1988-04-01 | 1988-04-01 | Electrochemical production method of barbituric acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7809088A JPH0730045B2 (en) | 1988-04-01 | 1988-04-01 | Electrochemical production method of barbituric acid derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01254668A true JPH01254668A (en) | 1989-10-11 |
| JPH0730045B2 JPH0730045B2 (en) | 1995-04-05 |
Family
ID=13652152
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7809088A Expired - Lifetime JPH0730045B2 (en) | 1988-04-01 | 1988-04-01 | Electrochemical production method of barbituric acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0730045B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541731A (en) * | 2016-02-22 | 2016-05-04 | 山东新华制药股份有限公司 | Method for preparing 5-ethyl-5-(1-methylbutyl)malonylurea |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110467575B (en) * | 2019-09-12 | 2021-06-22 | 公安部物证鉴定中心 | Synthesis and preparation method of phenobarbital-D5 for court science qualitative and quantitative use |
-
1988
- 1988-04-01 JP JP7809088A patent/JPH0730045B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105541731A (en) * | 2016-02-22 | 2016-05-04 | 山东新华制药股份有限公司 | Method for preparing 5-ethyl-5-(1-methylbutyl)malonylurea |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0730045B2 (en) | 1995-04-05 |
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