JPS6112906B2 - - Google Patents
Info
- Publication number
- JPS6112906B2 JPS6112906B2 JP54163305A JP16330579A JPS6112906B2 JP S6112906 B2 JPS6112906 B2 JP S6112906B2 JP 54163305 A JP54163305 A JP 54163305A JP 16330579 A JP16330579 A JP 16330579A JP S6112906 B2 JPS6112906 B2 JP S6112906B2
- Authority
- JP
- Japan
- Prior art keywords
- uracil
- catalyst
- cyanoacetylurea
- hydrogen
- palladium
- 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
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 46
- 229940035893 uracil Drugs 0.000 claims description 23
- QJGRPCPCQQPZLZ-UHFFFAOYSA-N n-carbamoyl-2-cyanoacetamide Chemical compound NC(=O)NC(=O)CC#N QJGRPCPCQQPZLZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000006722 reduction reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000004705 aldimines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- GKRZNOGGALENQJ-UHFFFAOYSA-N n-carbamoylacetamide Chemical compound CC(=O)NC(N)=O GKRZNOGGALENQJ-UHFFFAOYSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
Description
【発明の詳細な説明】
ウラシルは核酸中に存在するもので、このもの
自体に各種の生物学的活性が認められている他、
各種の医薬品の合成の中間体として用いられてお
り、有用な化合物である。ウラシルの合成方法と
しては、既に数多くの方法が発表されているが、
本発明は、工業的に極めて有利なウラシルの製造
方法を提供するものである。[Detailed Description of the Invention] Uracil is present in nucleic acids, and has been shown to have various biological activities.
It is a useful compound that is used as an intermediate in the synthesis of various pharmaceuticals. Many methods have already been announced for the synthesis of uracil, but
The present invention provides an industrially extremely advantageous method for producing uracil.
シアノアセチル尿素よりウラシルの合成につい
ては、Rupe等（H.Rupe，A.Metzger，H.
Vogler：Helvetica Chimica Acta8巻850頁
1925年）が、大量のニツケル触媒を用いてシアノ
アセチル尿素を接触還元を行つて、ウラシルの合
成を報告している。又、Nesterov等
（Nesterov，Safonova：C.A.70巻 1969年
87733h）は、酢酸の存在下に大量のニツケル触
媒を用いてシアノアセチル尿素の接触還元を行
い、ウラシルの合成を報告している。 Regarding the synthesis of uracil from cyanoacetylurea, Rupe et al. (H. Rupe, A. Metzger, H.
Vogler: Helvetica Chimica Acta 8 volumes 850 pages
(1925) reported the synthesis of uracil by catalytic reduction of cyanoacetylurea using a large amount of nickel catalyst. Also, Nesterov et al. (Nesterov, Safonova: CA70 volume 1969)
87733h) reported the synthesis of uracil by catalytic reduction of cyanoacetylurea using a large amount of nickel catalyst in the presence of acetic acid.
これ等の方法によれば、原料シアノアセチル尿
素に対して1.5〜２倍量と云う大量の還元触媒を
必要とし、しかもウラシルの得量は低く、又製品
に副生物を含み高品位の目的物を得る為には、精
製を繰り返し行わねばならない。 These methods require a large amount of reduction catalyst, 1.5 to 2 times the amount of the raw material cyanoacetylurea, and the yield of uracil is low, and the product contains by-products and does not contain high-quality target products. In order to obtain this, purification must be repeated repeatedly.
本発明者等は、シアノアセチル尿素を接触還元
するに際し、塩酸或は、硫酸等の強酸の存在下に
於て行えば、極めて小量の触媒により速かに還元
反応が進行し、しかも、高い収率にて副生物を含
まない高純度のウラシルが得られる事を見出し、
ウラシルの工業的有利な製造方法を発明した。 The present inventors have discovered that when catalytic reduction of cyanoacetyl urea is carried out in the presence of a strong acid such as hydrochloric acid or sulfuric acid, the reduction reaction proceeds quickly with an extremely small amount of catalyst, and also has a high We discovered that high purity uracil containing no by-products could be obtained in terms of yield.
Invented an industrially advantageous method for producing uracil.
シアノアセチル尿素よりウラシルの生成する過
程は、次式の如く
シアノアセチル尿素に１分子の水素の附加によ
りアルジミンを生成し、それの閉環反応によりウ
ラジルが生成すると考えられるが、本発明の強酸
の存在下に於ては、第一段の水素の附加反応が極
めて円滑に進む為、公知方法の如く大量の触媒を
必要とせず、極く少量の触媒により目的を達成す
る事が出来るばかりでなく、第二段の閉環反応も
順調に進む為、副生成物の生成も見られず、格別
の精製操作を行う事なく、高純度のウラシルが好
収率にて得られるのである。 The process of producing uracil from cyanoacetylurea is as shown in the following formula: It is thought that the addition of one molecule of hydrogen to cyanoacetyl urea produces aldimine, and the ring-closing reaction produces uradyl, but in the presence of the strong acid of the present invention, the first stage hydrogen addition reaction Because the process proceeds extremely smoothly, not only does it not require a large amount of catalyst as in known methods, but the objective can be achieved with a very small amount of catalyst.The second stage ring-closing reaction also proceeds smoothly, resulting in less by-products. There is no formation of uracil, and high purity uracil can be obtained in good yield without any special purification operations.
本発明の方法を実施するに際しては、還元触媒
としてはパラジウム系、白金系等の耐酸性の触媒
が適当で、例えば、５％パルジウム−カーボン粉
末を使用する場合、原料シアノアセチル尿素に対
し、50分の１量程度の使用で、室温に於て充分時
間内に還元反応と完了する事が出来る。反応温度
は、大体20〜70℃辺りが最も適している。還元反
応を低温にて進め、還元反応完了後、温度を上げ
て閉環反応を完結せしめると好結果が得られる。
低温に於て還元反応を進める事が出来るので、強
酸の存在下に於ても、原料のシアノアセチル尿素
が加水分解を受ける事なく、目的の反応を進める
事が出来る。 When carrying out the method of the present invention, an acid-resistant catalyst such as palladium-based or platinum-based catalyst is suitable as the reduction catalyst. For example, when using 5% paldium-carbon powder, 50% By using about 1/2 of the amount, the reduction reaction can be completed within a sufficient time at room temperature. The most suitable reaction temperature is approximately 20 to 70°C. Good results can be obtained by proceeding with the reduction reaction at a low temperature and, after completion of the reduction reaction, raising the temperature to complete the ring-closing reaction.
Since the reduction reaction can proceed at low temperatures, the desired reaction can proceed without the raw material cyanoacetylurea undergoing hydrolysis even in the presence of strong acids.
本発明の原料となるシアノアセチル尿素は、シ
アノ酢酸と尿素より容易に製造される化合物であ
つて、本発明の方法は工業的に有利なウラシルの
製造方法である。以下に実施例をもつて本発明の
方法を説明する。 Cyanoacetylurea, which is a raw material for the present invention, is a compound that is easily produced from cyanoacetic acid and urea, and the method of the present invention is an industrially advantageous method for producing uracil. The method of the present invention will be explained below with reference to Examples.
実施例 １
シアノアセチル尿素60ｇに水300c.c.、５％パラ
ジウム−カーボン粉末２ｇ、35％塩酸60ｇを加
え、30℃前後に於て水素気流中に激しく撹拌す
る。３〜４時間にて当量の水素を吸収する。後、
尚１時間60〜80℃に加温する。次で苛性ソーダ水
溶液を加えて析出したウラシルを溶解し、触媒を
ろ別して後、中和すればウラシルを析出する。得
量48.6ｇ、収率91.8％。Example 1 300 c.c. of water, 2 g of 5% palladium-carbon powder, and 60 g of 35% hydrochloric acid were added to 60 g of cyanoacetylurea, and the mixture was vigorously stirred in a hydrogen stream at around 30°C. The equivalent amount of hydrogen is absorbed in 3-4 hours. rear,
Further, heat to 60-80°C for 1 hour. Next, an aqueous solution of caustic soda is added to dissolve the precipitated uracil, the catalyst is filtered off, and the mixture is neutralized to precipitate uracil. Amount obtained: 48.6g, yield 91.8%.
U.V.：Ｅ１％１cm（260nｍ）＝730.5
TLC：メルク社製 キーゼルゲル 60F 254
（展開液 ｎ−プロパノール・28％アンモニア
水・水、６：３：１）単一スポツト Rf≒0.7
実施例 ２
シアノアセチル尿素50ｇに水300c.c.、５％パラ
ジウム−カーボン粉末２ｇ、硫酸30ｇを加え、30
〜40℃に於て水素気流中で激しく撹拌する。当量
の水素の吸収の後、尚１時間60〜70℃に加温す
る。苛性ソーダ水溶液を加えて析出したウラシル
を溶解触媒をろ別して後、中和すればウラシルの
結晶を析出する。UV: E 1 % 1 cm (260nm) = 730.5 TLC: Merck Kieselgel 60F 254 (Developing solution n-propanol/28% ammonia water/water, 6:3:1) Single spot Rf≒0.7 Example 2 Cyano Add 300 c.c. of water, 2 g of 5% palladium-carbon powder, and 30 g of sulfuric acid to 50 g of acetylurea.
Stir vigorously in a hydrogen stream at ~40°C. After uptake of an equivalent amount of hydrogen, the mixture is heated to 60-70° C. for another hour. When a caustic soda aqueous solution is added and the precipitated uracil is filtered to remove the dissolved catalyst, it is neutralized to precipitate uracil crystals.
実施例 ３
シアノアセチル尿素50ｇに水500c.c.、５％パラ
ジウム−カーボン粉末１ｇ、35％塩酸50ｇを加
え、25〜40℃に於て水素気流中激しく撹拌する。
当量の水素を吸収して後、尚１時間70〜80℃に加
温する。後、実施例１と同様に処理してウラシル
を得る。Example 3 500 c.c. of water, 1 g of 5% palladium-carbon powder, and 50 g of 35% hydrochloric acid are added to 50 g of cyanoacetylurea, and the mixture is vigorously stirred in a hydrogen stream at 25 to 40°C.
After absorbing an equivalent amount of hydrogen, the mixture is heated to 70-80° C. for another hour. Thereafter, the same treatment as in Example 1 is carried out to obtain uracil.
実施例 ４
シアノアセチル尿素60ｇに水270c.c.、５％パラ
ジウム−カーボン粉末３ｇ、35％塩酸55ｇを加
え、25〜30℃に於て水素気流中激しく撹拌する。
35時間にて当量の水素を吸収する。更に35％塩酸
15ｇを加え、１時間60〜80℃に加温する。後苛性
ソーダ水溶液を加えて析出したウラシルを溶解
し、触媒をろ別し、ろ液を中和してウラシルを得
る。得量49.8ｇ、収率94％。Example 4 270 c.c. of water, 3 g of 5% palladium-carbon powder, and 55 g of 35% hydrochloric acid are added to 60 g of cyanoacetylurea, and the mixture is vigorously stirred in a hydrogen stream at 25 to 30°C.
Absorbs equivalent amount of hydrogen in 35 hours. Additionally 35% hydrochloric acid
Add 15g and heat to 60-80℃ for 1 hour. After that, an aqueous solution of caustic soda is added to dissolve the precipitated uracil, the catalyst is filtered off, and the filtrate is neutralized to obtain uracil. Amount obtained: 49.8g, yield 94%.
実施例 ５
シアノアセチル尿素60ｇに水450c.c.、５％パラ
ジウム−カーボン粉末３ｇ、35％塩酸80ｇを加
え、30゜〜40゜附近に於て水素気流中激しく撹拌
する３〜４時間にて当量の水素を吸収する。直ち
に濾過して触媒、パラジウム−カーボン粉末を濾
別する。濾液を水浴上１時間加熱すればウラシル
を析出する。冷却後濾取、水洗する。ウラシル得
量45.5ｇ。Example 5 Add 450 c.c. of water, 3 g of 5% palladium-carbon powder, and 80 g of 35% hydrochloric acid to 60 g of cyanoacetylurea, and stir vigorously in a hydrogen stream at around 30° to 40° for 3 to 4 hours. Absorbs an equivalent amount of hydrogen. Immediately filter to remove catalyst and palladium-carbon powder. The filtrate is heated on a water bath for 1 hour to precipitate uracil. After cooling, filter and wash with water. Uracil yield: 45.5g.
Claims (1)
パラジウム系触媒を使用し、接触還元することを
特徴とするウラシルの製造法。1 Cyanoacetylurea in the presence of a strong acid,
A method for producing uracil, which is characterized by catalytic reduction using a palladium-based catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16330579A JPS5686172A (en) | 1979-12-15 | 1979-12-15 | Preparation of uracil |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16330579A JPS5686172A (en) | 1979-12-15 | 1979-12-15 | Preparation of uracil |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5686172A JPS5686172A (en) | 1981-07-13 |
| JPS6112906B2 true JPS6112906B2 (en) | 1986-04-10 |
Family
ID=15771295
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16330579A Granted JPS5686172A (en) | 1979-12-15 | 1979-12-15 | Preparation of uracil |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5686172A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5838268A (en) * | 1981-09-01 | 1983-03-05 | Ube Ind Ltd | Preparation of uracil |
| JPS58172376A (en) * | 1982-04-02 | 1983-10-11 | Yodogawa Seiyaku Kk | Preparation of 5-ethyluracil |
-
1979
- 1979-12-15 JP JP16330579A patent/JPS5686172A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5686172A (en) | 1981-07-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4012568B2 (en) | Method for producing halo-substituted aromatic acid | |
| JPS60215657A (en) | Preparation of n-acylphenylalanine | |
| JPS6112906B2 (en) | ||
| JP2577405B2 (en) | Method for producing 2,4,5-triamino-6-hydroxypyrimidine | |
| US2569288A (en) | Preparation of n-benzyl-betahalopropionamides | |
| JPS5855485A (en) | Purification of guanine | |
| JPH0549928A (en) | Regeneration of active carbon | |
| US5914399A (en) | Method for producing 5-isopropyluracil | |
| JPH0774184B2 (en) | 4,4'-diaminodiphenyl compound | |
| JP3317737B2 (en) | Method for producing catalyst for cyanhydrin hydration | |
| EP0034398B1 (en) | Production of 2-naphthylamine-4,8-disulphonic acid | |
| JP2824394B2 (en) | Catalyst for producing fumaric acid and method for producing fumaric acid using the catalyst | |
| JP2001151761A (en) | Method for producing uracil of thymine | |
| JP2664761B2 (en) | Method for producing aminobenzanthrones | |
| JPH09176101A (en) | Production of p-nitrophenylhydrazine | |
| JPH0737417B2 (en) | Method for purifying 4,4'-biphenyldicarboxylic acid | |
| JPS585184B2 (en) | Method for producing n-propyl-n-propylideneacetamide | |
| JP4032825B2 (en) | Method for producing 3,4-dihydroxybenzonitrile | |
| JP3544694B2 (en) | Method for producing N-tert-butyl-2-piperazinecarboxamides | |
| JPH0717953A (en) | Production of 5-isopropyluracil | |
| JPS5993060A (en) | Preparation of cytosines | |
| JPS6317065B2 (en) | ||
| JPS62164660A (en) | Production of methyl 2-sulfamidobenzoate | |
| JPS63303947A (en) | Production of o-formylbenzoic acid | |
| JPH08151216A (en) | Production of tetraammine-platinum (ii) dichloride |