JPS6366173A - Production of uracil derivative - Google Patents
Production of uracil derivativeInfo
- Publication number
- JPS6366173A JPS6366173A JP20922286A JP20922286A JPS6366173A JP S6366173 A JPS6366173 A JP S6366173A JP 20922286 A JP20922286 A JP 20922286A JP 20922286 A JP20922286 A JP 20922286A JP S6366173 A JPS6366173 A JP S6366173A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- compound
- item
- general 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.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 title abstract description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- -1 urea compound Chemical class 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 13
- AGSPXMVUFBBBMO-UHFFFAOYSA-N beta-aminopropionitrile Chemical class NCCC#N AGSPXMVUFBBBMO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000004202 carbamide Substances 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 8
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000012948 isocyanate Substances 0.000 claims description 3
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 4
- 239000000126 substance Substances 0.000 claims 4
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 18
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 12
- FENJKTQEFUPECW-UHFFFAOYSA-N 3-anilinopropanenitrile Chemical compound N#CCCNC1=CC=CC=C1 FENJKTQEFUPECW-UHFFFAOYSA-N 0.000 abstract description 4
- 239000007864 aqueous solution Substances 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- IYBINJWRHRKLTJ-UHFFFAOYSA-N 1-phenyl-1,3-diazinane-2,4-dione Chemical compound O=C1NC(=O)CCN1C1=CC=CC=C1 IYBINJWRHRKLTJ-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 229920002554 vinyl polymer Polymers 0.000 abstract 1
- 235000011007 phosphoric acid Nutrition 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000011907 photodimerization Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000009489 vacuum treatment Methods 0.000 description 1
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
訳卒津の利用分野
本発明はウラノル誘導体の製造方法、より詳細にはノア
ノエチルアミン誘導体を出発原料とするウラシル誘導体
の製造方法の改良に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for producing uranol derivatives, and more particularly to an improvement in a method for producing uracil derivatives using a noanoethylamine derivative as a starting material.
従迷の技術
ウラシル誘導体のなかには、制ガン作用、抗ウィルス作
用、抗菌作用または殺虫作用等の生理活性を有する化合
物が多く含まれており、また、このような生理活性を有
する化合物の中間体としても重要なものが多いだけでな
く、紫外線による光二量化物は集積回路等のレンスト材
料として近年注目を浴びつつある。Unconventional technology Uracil derivatives contain many compounds that have physiological activities such as anticancer, antiviral, antibacterial, and insecticidal activities, and are also used as intermediates for such physiologically active compounds. Not only are there many important materials, but photodimerization products caused by ultraviolet rays have been attracting attention in recent years as resist materials for integrated circuits and the like.
ウラシル誘導体の製造法としてンアノエチルアミン誘導
体を出発原料とする方法、例えばンアノエチルアミン誘
導体とイソ７アン酸のアルカリ金属塩を塩酸水溶液中で
反応させる方法が知られている。As a method for producing uracil derivatives, a method is known in which a n-anoethylamine derivative is used as a starting material, such as a method in which a n-anoethylamine derivative is reacted with an alkali metal salt of isoheptanoic acid in an aqueous hydrochloric acid solution.
＆唯外眸沫しようζ±１問題一点
しかしながら、この製造法の場合には、イソンアン酸塩
が塩酸水溶液中で不安定なイソシ）′ン酸水素となって
速やかに分解するために、比較的結晶性が高くて水に難
溶性のンアノエチルアミン誘導体との反応が困難となり
、収率が非常に低くム゛るという欠点がある。& Just a quick look ζ±1 One problem However, in the case of this production method, isone anhydride rapidly decomposes into unstable hydrogen isocyanate in an aqueous hydrochloric acid solution, so the production process is relatively slow. The drawback is that it is difficult to react with the highly crystalline and slightly water-soluble anoethylamine derivative, resulting in a very low yield.
本発明は、ノアノエチルアミン誘導体を出発原料として
ウラシル誘導体を製造する従来法のこのような欠点を改
良するためになされ八〇のである。The present invention was made in order to improve these drawbacks of the conventional method of producing uracil derivatives using noanoethylamine derivatives as starting materials.
本発明は一般式［Ｉ］： ＲＩ Ｒ。The present invention relates to general formula [I]: R.I. R.
（式中、Ｒ１は水素原子、炭＊ Ｊ＋７． ｒ数１〜５
ノアルキル、アリールまたはビニル基、１１２は水素
側子、炭素原子数Ｉ〜５のアルキルまたはアリール基、
Ｙは酸素原子、硫黄原子またはイミノ基を表ず）で表わ
される化合物をりん酸の存在下、加熱環化することを特
徴とする、
一般式［■］：
（式中、Ｒ８、Ｒ３およびＹは前記と同意義）で表わさ
れるウラシル誘導体の製造方法に関する。(In the formula, R1 is a hydrogen atom, carbon * J + 7. r number 1 to 5
noalkyl, aryl or vinyl group, 112 is a hydrogen pendant, an alkyl or aryl group having I to 5 carbon atoms,
General formula [■]: (wherein, R8, R3 and Y is the same meaning as above).
一般式［１］で表わされる化合物は、以下のごとき方法
で製造することができる。The compound represented by the general formula [1] can be produced by the following method.
即ち、Ｒ７が水素である化合物［１］は、一般式［］
％式％［１１］
（式中、Ｒ１は水素原子、炭素原子数１〜５のアルキル
基、アリール基またはビニル基を示す）で表わされるン
アノエチルアミン誘導体と一般式［ＩＶ］：
Ｎ １−１２
Ｙ＝Ｃ［ＩＶ］
ノ基を示す）
で表わされる尿素化合物とを鉱酸水溶液中で反応させる
ことにより得られる。本発明台らは上記反応において鉱
酸としてりん酸を用いると化合物［ｒ］の収率が著しく
向上することを見出した。That is, the compound [1] in which R7 is hydrogen has the general formula [ ] % formula % [11] (wherein R1 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an aryl group, or a vinyl group) It can be obtained by reacting an anoethylamine derivative represented by the formula [IV] with a urea compound represented by the general formula [IV]: N 1-12 Y=C[IV] represents a group in an aqueous mineral acid solution. The inventors of the present invention have found that when phosphoric acid is used as the mineral acid in the above reaction, the yield of compound [r] is significantly improved.
りん酸を使用する場合、りん酸は７０重１−１１％以上
の水溶液として用いるのが適当である。When phosphoric acid is used, it is appropriate to use it as an aqueous solution of 70% by weight or more, 1-11% or more.
リン酸としては通常、正リン酸または無水リン酸を使用
するが、ポリリン酸、メタリン酸およびピロリン酸等の
重合リン酸を使用して６．１−い。Normally, orthophosphoric acid or phosphoric anhydride is used as the phosphoric acid, but polymerized phosphoric acids such as polyphosphoric acid, metaphosphoric acid, and pyrophosphoric acid can also be used.
リン酸の使用量はシアノエチルアミン誘導体に対して通
常１当量以上、好ましくは２〜１０当１７ｔである。The amount of phosphoric acid used is usually 1 equivalent or more, preferably 17 tons per 2 to 10 equivalents, based on the cyanoethylamine derivative.
反応温度は２０〜１１０℃が適゛１１であり、それ以」
二の温度で反応すると後述するごとく、生成した化合物
［１］の環化が同時に進行し、ウラシル誘導体［ＴＩ］
が得られる。Suitable reaction temperature is 20 to 110°C, 11.
As will be described later, when the reaction occurs at the second temperature, the cyclization of the generated compound [1] proceeds simultaneously, and the uracil derivative [TI]
is obtained.
−に記反応で得られる化合物［１］は、冷却して水を加
えろと結晶として単離できる。Compound [1] obtained by the reaction described in - can be isolated as crystals by cooling and adding water.
本発明ウラシル誘導体［ｎ］は」二記化合物［１］を単
離後りん酸の存在下に加熱（１１Ｏ〜２００℃、好まし
くは１２０〜１７０℃）すると環化して得られる。しか
しながら、本発明ウラシル誘導体［ｒｌ］は上記化合物
［１］を単離することなく、シアノエチルアミン誘導体
［Ｉ１１］と尿素化合物［ＩＶＪの一段反応によっても
得ることができる。この場合、ウラシル誘導体［１１］
は化合物［１］を経由して合成されるものと考えられる
。りん酸濃度は前述の通りであり、反応温度も当初低温
（好ましくは２０〜１１０°Ｃ）で、次いて１１０〜２
００℃に昇温して行なってもよい。The uracil derivative [n] of the present invention is obtained by cyclizing the compound [1] described above by heating it in the presence of phosphoric acid (110 to 200°C, preferably 120 to 170°C). However, the uracil derivative [rl] of the present invention can also be obtained by a one-step reaction of the cyanoethylamine derivative [I11] and the urea compound [IVJ] without isolating the above compound [1]. In this case, the uracil derivative [11]
is considered to be synthesized via compound [1]. The phosphoric acid concentration is as described above, and the reaction temperature is initially low (preferably 20-110°C), then 110-210°C.
The temperature may be raised to 00°C.
化合物［１］においてＲ３が水素以外の基の場合、例え
ば炭素数１〜５のアルキル基やアリール基の場合は尿素
化合物［］Ｖ］に代えて相当するイソシアン酸エステル
［Ｖ］を使用すればよい。反応条件は尿素化合物を用い
る場合と同様である。When R3 in compound [1] is a group other than hydrogen, for example, an alkyl group or aryl group having 1 to 5 carbon atoms, the corresponding isocyanate ester [V] can be used instead of the urea compound []V]. good. The reaction conditions are the same as when using a urea compound.
本発明において使用する一般式１ｉ ＩＩ＋ ］で表イ
っされるシアノエチルアミン誘導体は例えばアクリ〔ノ
ニトリルとアミン類を反応させることによって調製する
ことができ、特にシアノエチルアミノベンゼン誘導体が
好ましい。The cyanoethylamine derivative represented by the general formula 1i II+ used in the present invention can be prepared, for example, by reacting acryl[nonitrile with an amine, and cyanoethylaminobenzene derivatives are particularly preferred.
一般式［１１１］において、Ｒ１は水素原子、炭素原子
数１〜５のアルキル基、例えばメチル基、」−デル基、
ｎ−プロピル基、イソプロピル塙、ｎ−ゾヂル基、ｎ−
ペンチル基等、アリール基またはビニル基を示す。アリ
ール基としてはフＪニルノー１：、ナフチル基等であっ
て、置換基、例えばメチル、エチル等の低級アルキル基
、ハロゲン原子、カルボキシル基、アルコキシカルボニ
ル基、ニド「１基、スルポン基等を有してもよい。ビニ
ル」ｋとしてはビニル基、アリル基、１−プロペニル基
、イソプロペニル基等が例示される。In the general formula [111], R1 is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, such as a methyl group, a "-del group,
n-propyl group, isopropyl group, n-zodyl group, n-
Indicates an aryl group such as a pentyl group or a vinyl group. Examples of the aryl group include a naphthyl group, a substituent such as a lower alkyl group such as methyl or ethyl, a halogen atom, a carboxyl group, an alkoxycarbonyl group, a nido group, a sulfone group, etc. Examples of the vinyl group include a vinyl group, an allyl group, a 1-propenyl group, and an isopropenyl group.
本発明に用いられる尿素化合物［ＩＶＪの具体例として
は、尿素、チオ尿素、グアニジノ等が例示される。Specific examples of the urea compound [IVJ] used in the present invention include urea, thiourea, guanidino, and the like.
一般式［Ｖ］で表イっされるイソシアン酸エステルとし
てはイソシアン酸のメチルエステル、エチルエステル、
イソプロピルエステル、ｎ−プロピルエステル、ｎ−ブ
チルエステル、ｔ−ブチルエステルまたはフェニルエス
テル等が例示される。Examples of the isocyanate ester represented by the general formula [V] include methyl ester, ethyl ester,
Examples include isopropyl ester, n-propyl ester, n-butyl ester, t-butyl ester, and phenyl ester.
以下、本発明を実施例によって説明する。Hereinafter, the present invention will be explained by examples.
実施例ｌ
Ｎ−２−シアノエチルアニリン１０ｇ（６８，５ｍｍｏ
ｌ）および尿素１０ｇ（＋ ６７ｍｍｏｌ）を８５％リ
ン酸水溶液５０ｉＱに加えた反応液を撹拌下、１１０℃
で５時間反応させ、反応混合物を１６０℃で５時間減圧
処理に付した後、冷却し、生成した赤色固体に水４００
ｍ（ｌを加え、析出した白色沈澱物を濾取し、エタノ
ールから再結晶させることによって１−フェニルジヒド
ロウラシル３．３ｇを得た（ｍ、ｐ、：Ｉ９４〜１９６
℃、ＩＲスペクトルおよび’Ｈ−ＮＭｒ（をそれぞれ第
１図および第２図に示す）。Example l 10 g of N-2-cyanoethylaniline (68.5 mmo
1) and 10 g (+ 67 mmol) of urea were added to 50 iQ of an 85% phosphoric acid aqueous solution, and the reaction mixture was heated at 110°C with stirring.
The reaction mixture was subjected to a vacuum treatment at 160°C for 5 hours, cooled, and the red solid produced was poured with water at 400 °C.
m(l) was added, the precipitated white precipitate was collected by filtration, and recrystallized from ethanol to obtain 3.3 g of 1-phenyldihydrouracil (m, p,: I94-196
°C, IR spectra and 'H-NMr (shown in Figures 1 and 2, respectively).
衷湾！１１ Ｎ−２−シアノエチルアニリン２．０ｇ（＋４ｍｍ。Ying Wan! 11 N-2-cyanoethylaniline 2.0g (+4mm.
ｌ）に嫌気条件下にイソノアン酸フＪニル１８３尻θ（
１７ｍｍｏｌ）およびトリエチルアミン０ 、５ ｍＯ
を加えた反応液を室温で４時間撹拌した後、８５％リン
酸水溶液１０１１１１！を加え、撹拌下、１３０℃で６
時間反応させ、冷却後、反応混合物に水５０ｍ０を加え
、析出した沈澱物を濾取し、エタノールから再結晶させ
ることによって、Ｉ、３− ノフＪニルジヒドロウラシ
ル１．Ｏｇを得た（ｍ、ｐ、 ： ２２９〜２３０℃
、ＩＲスペクトルおＪ二び’Ｉｔ ＮＭＩえをそれぞ
れ第３図および第４図に示す）３゜寒施桝±
Ｎ−２−ソアノエチルアニリン３５１／（０，２／１ｍ
ａｔ）に嫌気条件下にイソンアン酸イソブ［７ビル２８
．９ｇ（０，３４ｍｏｌ）およびトリエチルアミン１２
゜４Ｍρを加えた反応液を室温で２時間撹拌しＮ−イソ
プロピル−Ｎ′ −（２−ンアノエチル） Ｎ′フェニ
ル尿素を得た。（ｍ、ｐ、 ニア Ｇ〜７７℃、］Ｒお
よび’ Ｈ−Ｎ Ｍ Ｒをそれぞれ第５図および第６図
に示す）。l) under anaerobic conditions isonoanoic acid phenyl 183 butt θ (
17 mmol) and triethylamine 0,5 mO
After stirring the reaction solution at room temperature for 4 hours, 85% phosphoric acid aqueous solution 101111! and stirred at 130℃ for 6 hours.
After reacting for an hour and cooling, 50 m of water was added to the reaction mixture, the precipitate was collected by filtration, and recrystallized from ethanol to give I,3-NofJnyldihydrouracil 1. Obtained Og (m, p,: 229-230°C
, IR spectra and NMI values are shown in Figures 3 and 4, respectively)
at) under anaerobic conditions.
．． 9 g (0.34 mol) and triethylamine 12
The reaction solution to which 4 Mρ was added was stirred at room temperature for 2 hours to obtain N-isopropyl-N'-(2-anoethyl)N'phenylurea. (m, p, near G~77°C, ]R and 'H-NMR shown in Figures 5 and 6, respectively).
次いで８５％リン酸水溶液２０ （ｌ ｍ（ｌを加え、
撹拌下、１３０℃で６時間反応させることによって１−
フェニル−３−イソプロビルシヒドロウラシを得た。Then add 20 (l m) of 85% aqueous phosphoric acid solution,
1- by reacting at 130°C for 6 hours with stirring.
Phenyl-3-isoprobyl dihydrouraci was obtained.
羽叩μ抜薇
本発明方法に、にり、医薬や農薬等として有用なウラノ
ル誘導体お、１びこれらの化合物の中間体として有用な
ウラシル誘導体を比較的温和な条件下で収率よく簡便に
製造することができる。Using the method of the present invention, uranol derivatives useful as medicines, agricultural chemicals, etc., and uracil derivatives useful as intermediates for these compounds can be easily produced in high yield under relatively mild conditions. be able to.
第１図および第２図は１−フェニルジヒドロウラノルの
ｌ ＩＮおよびＪｌ−ＮＭＲのヂャート、第３図および
第４図はＩ、３−ジフェニルンヒドロウラフルのＩＲお
よび’■１−ＮＩＶｆＲのヂャートおよび第５図および
第６図はＮ−イソプロピル−Ｎ′ （２−ンアノエチル
）−Ｎ′−フェニル尿素のＩＲおよび’Ｉ−ｌ−１−Ｎ
のヂャートをそれぞれ示す。Figures 1 and 2 are 1IN and Jl-NMR charts of 1-phenyldihydrouranol, and Figures 3 and 4 are IR and The diagram and Figures 5 and 6 show the IR and 'I-l-1-N of N-isopropyl-N'(2-oneanoethyl)-N'-phenylurea.
The diagrams of each are shown below.
Claims (1)
ル、アリールまたはビニル基、Ｒ＿２は水素原子、炭素
原子数１〜５のアルキルまたはアリール基、Ｙは酸素原
子、硫黄原子またはイミノ基を表わす）で表わされる化
合物をりん酸の存在下、加熱環化することを特徴とする
、一般式［II］：▲数式、化学式、表等があります▼［
II］ （式中、Ｒ＿１、Ｒ＿２およびＹは前記と同意義）で表
わされるウラシル誘導体の製造法。 ２、Ｒ＿１がアリール基である第１項記載の製造法。 ３、Ｙが酸素原子である第１項記載の製造法。 ４、Ｒ＿２が水素原子である第１項の製造法。 ５、加熱を１２０〜１７０℃で行なう第１項記載の製造
法。 ６、一般式［III］： ＮＣ−ＣＨ＿２ＣＨ＿２−ＮＨ−Ｒ＿１［III］（式中
、Ｒ＿１は水素原子、炭素原子数１〜５のアルキル基、
アリール基またはビニル基を示す）で表わされるシアノ
エチルアミン誘導体、および一般式［IV］： ▲数式、化学式、表等があります▼［IV］ （式中、Ｙは酸素原子、イオウ原子またはイミノ基を示
す） で表わされる尿素化合物または 一般式［Ｖ］： Ｏ＝Ｃ＝Ｎ−Ｒ＿３［Ｖ］ （式中、Ｒ＿３は炭素原子数１〜５のアルキル基または
アリール基を示す） で表わされるイソシアン酸エステルをリン酸の存在下に
反応させることを特徴とする、 一般式［II］： ▲数式、化学式、表等があります▼［II］ （式中、Ｒ＿１およびＹは前記と同意義であり、Ｒ＿２
は水素原子、炭素原子数１〜５のアルキル基またはアリ
ール基を示す） で表わされるウラシル誘導体の製造法。 ７、Ｒ＿１がアリール基である第６項記載の製造法。 ８、Ｙが酸素原子である第６項記載の製造法。 ９、シアノエチルアミン誘導体［III］と尿素化合物［
IV］またはイソシアン酸エステル［Ｖ］の反応を予め２
０〜１１０℃で行ない、次いで１１０〜２００℃で反応
させる第６項記載の製造法。[Claims] 1. General formula [I]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] (In the formula, R_1 is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an aryl group, or a vinyl group, R_2 is a hydrogen atom, an alkyl or aryl group having 1 to 5 carbon atoms, and Y is an oxygen atom, a sulfur atom, or an imino group) is heated and cyclized in the presence of phosphoric acid. , General formula [II]: ▲ Contains mathematical formulas, chemical formulas, tables, etc. ▼ [
II] (wherein R_1, R_2 and Y have the same meanings as above). 2. The production method according to item 1, wherein R_1 is an aryl group. 3. The production method according to item 1, wherein Y is an oxygen atom. 4. The manufacturing method of item 1, wherein R_2 is a hydrogen atom. 5. The manufacturing method according to item 1, wherein heating is performed at 120 to 170°C. 6. General formula [III]: NC-CH_2CH_2-NH-R_1 [III] (wherein R_1 is a hydrogen atom, an alkyl group having 1 to 5 carbon atoms,
Cyanoethylamine derivatives represented by aryl or vinyl groups) and general formula [IV]: ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [IV] (In the formula, Y represents an oxygen atom, a sulfur atom, or an imino group. ) or isocyanic acid represented by the general formula [V]: O=C=N-R_3[V] (wherein R_3 represents an alkyl group or aryl group having 1 to 5 carbon atoms) General formula [II], characterized by reacting an ester in the presence of phosphoric acid: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] (In the formula, R_1 and Y have the same meanings as above, R_2
represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, or an aryl group. 7. The production method according to item 6, wherein R_1 is an aryl group. 8. The manufacturing method according to item 6, wherein Y is an oxygen atom. 9. Cyanoethylamine derivative [III] and urea compound [
IV] or isocyanate ester [V] in advance.
7. The production method according to item 6, wherein the reaction is carried out at 0 to 110°C and then reacted at 110 to 200°C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20922286A JPH0651682B2 (en) | 1986-09-05 | 1986-09-05 | Method for producing uracil derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20922286A JPH0651682B2 (en) | 1986-09-05 | 1986-09-05 | Method for producing uracil derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6366173A true JPS6366173A (en) | 1988-03-24 |
| JPH0651682B2 JPH0651682B2 (en) | 1994-07-06 |
Family
ID=16569371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20922286A Expired - Lifetime JPH0651682B2 (en) | 1986-09-05 | 1986-09-05 | Method for producing uracil derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0651682B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807864A (en) * | 1996-03-07 | 1998-09-15 | American Home Products Corporation | 2-thioxo-tetrahydropyrimidin-4-one derivatives |
-
1986
- 1986-09-05 JP JP20922286A patent/JPH0651682B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807864A (en) * | 1996-03-07 | 1998-09-15 | American Home Products Corporation | 2-thioxo-tetrahydropyrimidin-4-one derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0651682B2 (en) | 1994-07-06 |
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