WO2003010151A1 - Method for producing 4-methyl pyrimidine - Google Patents

Method for producing 4-methyl pyrimidine Download PDF

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Publication number
WO2003010151A1
WO2003010151A1 PCT/EP2001/008614 EP0108614W WO03010151A1 WO 2003010151 A1 WO2003010151 A1 WO 2003010151A1 EP 0108614 W EP0108614 W EP 0108614W WO 03010151 A1 WO03010151 A1 WO 03010151A1
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WIPO (PCT)
Prior art keywords
reaction
butanone
methylpyrimidine
formamidine
dialkoxy
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PCT/EP2001/008614
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German (de)
French (fr)
Inventor
Thomas GÜTHNER
Bernhard Graml
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Degussa Ag
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Publication date
Application filed by Degussa Ag filed Critical Degussa Ag
Priority to EP01969512A priority Critical patent/EP1409462A1/en
Priority to PCT/EP2001/008614 priority patent/WO2003010151A1/en
Priority to US10/451,092 priority patent/US6841672B2/en
Publication of WO2003010151A1 publication Critical patent/WO2003010151A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a process for the preparation of 4-methylpyrimidine, which is a valuable intermediate for the production of pharmaceuticals and crop protection agents.
  • the present invention was therefore based on the object of developing a technically simple process for the preparation of 4-methylpyrimidine which does not have the stated disadvantages of the prior art, but rather from technically available ones Raw materials under relatively mild reaction conditions provides good yields.
  • a 4,4-dialkoxy-2-butanone is reacted as a CV component with a formamidine salt as an NCN component.
  • 4,4-dialkoxy-2-butanones such.
  • B. 4,4-dimethoxy-butanone and 4,4-diethoxy-2-butanone are particularly suitable, the 4,4-dimethoxy-2-butanone which is readily available industrially to be regarded as particularly preferred.
  • Suitable formamidine salts are e.g. B. corresponding salts of carboxylic acids, hydrohalic acids or oxygen acids and in particular the acetate, the hydrochloride and the sulfate. These formamidine salts can be produced in a technically simple manner, such as. B. the formamidine acetate (see. DE-OS 38 08 767).
  • reaction of these two starting substances can be carried out with or without solvents or diluents (e.g. alcohols, esters or carboxylic acids) and with or without the addition of other substances, e.g. Catalysts (especially acids or acid salts) take place.
  • solvents or diluents e.g. alcohols, esters or carboxylic acids
  • other substances e.g. Catalysts (especially acids or acid salts) take place.
  • the reaction is preferably carried out without the addition of solvents or other substances.
  • the molar ratio of 4,4-dialkoxy-2-butanone to formarnidine salts is preferably between 1: 2 to 2: 1, in particular between 1.2: 1 to 1: 1.2.
  • the starting compounds can be introduced together, but it is easily possible to meter in one of the two starting components during the reaction.
  • the reaction according to the invention is carried out at temperatures from 80 to 180 ° C., preferably at 110 to 150 ° C.
  • Arising alcohol e.g. Methanol or ethanol can be refluxed. According to a preferred embodiment, however, it is continuously removed from the reaction mixture by distillation.
  • the reaction time is usually 0.5 to 48 hours, preferably 2 to 8 hours.
  • the reaction mixture is preferably cooled with water and a strong base, e.g. Sodium hydroxide solution, and the 4-methylpyrimidine is extracted in a known manner with an organic solvent (such as, for example, t-butyl methyl ether), and the 4-methylpyrimidine is purified by distillation after the solvent has been removed, the purification preferably being carried out with the aid of fractional distillation ,
  • a strong base e.g. Sodium hydroxide solution
  • an organic solvent such as, for example, t-butyl methyl ether
  • Example 1 (comparison according to Bredereck et. Al.)
  • the viscous reaction product was treated with 500 ml of water and 65 g
  • the total isolated yield was calculated to be 34.0%.
  • the mixture was cooled, mixed with 100 g of water and 65 g of 50% sodium hydroxide solution and extracted continuously with t-butyl methyl ether for a total of 20 hours.
  • the total isolated yield was calculated to be 61.8%.
  • the mixture was cooled, 300 g of water and 165.5 g of 50% sodium hydroxide solution were added and the mixture was extracted continuously with t-butyl methyl ether for a total of 20 hours.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention relates to a method for producing 4-methyl pyrimidine. A 4,4-dialkoxy-2-butanone is reacted with a formamidine salt, optionally in the presence of a solvent or a diluting agent, at temperatures of between 80 and 180 °C. The inventive method enables 4-methyl pyrimidine to be obtained in a significantly more simple manner and in larger quantities than with known methods.

Description

Verfahren zur Herstellung von 4-Methylpyrimidin Process for the preparation of 4-methylpyrimidine
Beschreibungdescription
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von 4-Methylpyrimidin, welches ein wertvolles Zwischenprodukt zur Herstellung von Pharmaka und Pflanzenschutzmitteln darstellt.The present invention relates to a process for the preparation of 4-methylpyrimidine, which is a valuable intermediate for the production of pharmaceuticals and crop protection agents.
Die Herstellung von 4-Methylpyrimidin ist im Prinzip bekannt. Neben mehreren sehr umständlichen indirekten Synthesen aus chlorhaltigen 4-Methylpyrimidinen durch Reduktion sind insbesondere Verfahren, bei denen eine C4-Komponente mit einer NCN- omponente umgesetzt wird, zur Herstellung geeignet.The production of 4-methylpyrimidine is known in principle. In addition to several very cumbersome indirect syntheses from chlorine-containing 4-methylpyrimidines by reduction, processes in which a C4 component is reacted with an NCN component are particularly suitable for the preparation.
Bredereck et. al. (Org. Synth. Coll. Vol. V, 794, Wiley 1973) beschreiben ein praktikables Verfahren ausgehend von Formamid und 4,4-Dimethoxy- 2-butanon, bei dem 4-Methylpyrimidin in einer Ausbeute von 54 bis 63 % erhalten wird. Nachteilig an diesem Verfahren ist jedoch, dass ein sehr großer Überschuss an Formamid (über 6 mol Formamid pro mol 4,4-Dimethoxy-2-butanon) erforderlich ist. Ein Teil dieses Formamids wird im Verlaufe der Reaktion zu Kohlenmonoxid zersetzt, was Handhabungsprobleme aufwirft. Der Rest des Formamids erschwert wegen seiner lösungsvermittelnden Eigenschaften die nachfolgende Extraktion des Produkts aus Wasser. Zudem benötigt die beschriebene Reaktion sehr hohe Temperaturen (180 bis 190 °C), was zu einer verstärkten Nebenproduktbildung führt.Bredereck et. al. (Org. Synth. Coll. Vol. V, 794, Wiley 1973) describe a practical process starting from formamide and 4,4-dimethoxy-2-butanone, in which 4-methylpyrimidine is obtained in a yield of 54 to 63%. However, a disadvantage of this process is that a very large excess of formamide (over 6 mol of formamide per mol of 4,4-dimethoxy-2-butanone) is required. Part of this formamide is decomposed to carbon monoxide in the course of the reaction, which poses handling problems. The rest of the formamide makes the subsequent extraction of the product from water difficult because of its solubilizing properties. In addition, the reaction described requires very high temperatures (180 to 190 ° C), which leads to increased by-product formation.
Die einzig bekannte alternative Direktsynthese ist die in DE-PS 822 086 beschriebene Umsetzung von Formamidinhydrochlorid mit dem kommerziell nicht erhältlichen 1,1,3,3-Tetramethoxybutan und methanolischem HC1.The only known alternative direct synthesis is the reaction of formamidine hydrochloride with the 1,1,3,3-tetramethoxybutane and methanolic HCl described in DE-PS 822 086.
Der vorliegenden Erfindung lag daher die Aufgabe zugrunde, ein technisch einfach durchzuführendes Verfahren zur Herstellung von 4-Methylpyrimidin zu entwickeln, welches die angeführten Nachteile des Standes der Technik nicht aufweist, sondern aus technisch verfügbaren Rohstoffen bei vergleichsweise milden Reaktionsbedingungen gute Ausbeuten liefert.The present invention was therefore based on the object of developing a technically simple process for the preparation of 4-methylpyrimidine which does not have the stated disadvantages of the prior art, but rather from technically available ones Raw materials under relatively mild reaction conditions provides good yields.
Diese Aufgabe wurde erfindungsgemäß dadurch gelöst, dass man ein 4,4-Dialkoxy-2-butanon mit einem Formamidinsalz ggf. in Gegenwart eines Löse- oder Verdünnungsmittels bei Temperaturen von 80 bis 180 °C umsetzt. Es hat sich hierbei überraschenderweise gezeigt, dass man mit Hilfe des erfindungsgemäßen Verfahrens 4-Methylpyrimidin auf wesentlich einfachere Weise und gleichzeitig in höheren Ausbeuten erhalten kann, als dies mittels bekannter Verfahren möglich ist.This object has been achieved according to the invention by reacting a 4,4-dialkoxy-2-butanone with a formamidine salt, if appropriate in the presence of a solvent or diluent, at from 80 to 180 ° C. It has surprisingly been found that 4-methylpyrimidine can be obtained in a much simpler manner and at the same time in higher yields than is possible using known processes with the aid of the process according to the invention.
Beim Verfahren entsprechend der vorliegenden Erfindung wird also ein 4,4-Dialkoxy-2-butanon als CV omponente mit einem Formamidinsalz als NCN-Komponente zur Umsetzung gebracht.In the process according to the present invention, a 4,4-dialkoxy-2-butanone is reacted as a CV component with a formamidine salt as an NCN component.
Als 4,4-Dialkoxy-2-butanone sind z. B. 4,4-Dimethoxy-butanon und 4,4-Diethoxy-2-butanon besonders geeignet, wobei das technisch leicht verfügbare 4,4-Dimethoxy-2-butanon als besonders bevorzugt anzusehen ist.As 4,4-dialkoxy-2-butanones such. B. 4,4-dimethoxy-butanone and 4,4-diethoxy-2-butanone are particularly suitable, the 4,4-dimethoxy-2-butanone which is readily available industrially to be regarded as particularly preferred.
Geeignete Formamidinsalze sind z. B. entsprechende Salze von Carbonsäuren, Halogenwasserstoffsäuren oder Sauerstoffsäuren und insbesondere das Acetat, das Hydrochlorid und das Sulfat. Diese Formamidinsalze sind auf technisch einfache Weise herstellbar, wie z. B. das Formamidinacetat (vgl. DE-OS 38 08 767).Suitable formamidine salts are e.g. B. corresponding salts of carboxylic acids, hydrohalic acids or oxygen acids and in particular the acetate, the hydrochloride and the sulfate. These formamidine salts can be produced in a technically simple manner, such as. B. the formamidine acetate (see. DE-OS 38 08 767).
Die Umsetzung dieser beiden Äusgangssubstanzen kann mit oder ohne Löse- oder Verdünnungsmittel (z. B. Alkoholen, Estern oder Carbonsäuren) sowie mit oder ohne Zusatz weiterer Stoffe, wie z.B. Katalysatoren (insbesondere Säuren oder saure Salze), erfolgen. Bevorzugt wird die Reaktion jedoch ohne Lösemittel oder Zusatz weiterer Stoffe durchgeführt.The reaction of these two starting substances can be carried out with or without solvents or diluents (e.g. alcohols, esters or carboxylic acids) and with or without the addition of other substances, e.g. Catalysts (especially acids or acid salts) take place. However, the reaction is preferably carried out without the addition of solvents or other substances.
Das Molverhältnis des 4,4-Dialkoxy-2-butanons zu Formarnidinsalzen liegt vorzugsweise zwischen 1 : 2 bis 2 : 1, insbesondere zwischen 1,2 : 1 bis 1 : 1,2. Die Ausgangsverbindungen können gemeinsam vorgelegt werden, es ist jedoch ohne Weiteres möglich, eine der beiden Ausgangskomponenten während der Reaktion zuzudosieren.The molar ratio of 4,4-dialkoxy-2-butanone to formarnidine salts is preferably between 1: 2 to 2: 1, in particular between 1.2: 1 to 1: 1.2. The starting compounds can be introduced together, but it is easily possible to meter in one of the two starting components during the reaction.
Die erfindungsgemäße Umsetzung wird bei Temperaturen von 80 bis 180 °C, vorzugsweise bei 110 bis 150 °C, durchgeführt. Entstehender Alkohol, wie z.B. Methanol oder Ethanol, kann refluxiert werden. Gemäß einer bevorzugten Ausführungsform wird er aber laufend destillativ aus dem Reaktiσnsgemisch entfernt. Die Reaktionsdauer beträgt in der Regel 0,5 bis 48 Stunden, vorzugsweise 2 bis 8 Stunden.The reaction according to the invention is carried out at temperatures from 80 to 180 ° C., preferably at 110 to 150 ° C. Arising alcohol, e.g. Methanol or ethanol can be refluxed. According to a preferred embodiment, however, it is continuously removed from the reaction mixture by distillation. The reaction time is usually 0.5 to 48 hours, preferably 2 to 8 hours.
Nach erfolgter Umsetzung wird das Reaktionsgemisch vorzugsweise abgekühlt, mit Wasser und einer starken Base, wie z.B. Natronlauge, versetzt und das 4-Methylpyrimidin in bekannter Weise mit einem organischen Lösemittel (wie z. B. t-Butylmethylether) extrahiert und das 4-Methylpyrimidin nach dem Entfernen des Lösemittels destillativ gereinigt, wobei die Aufreinigung vorzugsweise mit Hilfe einer fraktionierten Destillation durchgeführt wird.After the reaction is complete, the reaction mixture is preferably cooled with water and a strong base, e.g. Sodium hydroxide solution, and the 4-methylpyrimidine is extracted in a known manner with an organic solvent (such as, for example, t-butyl methyl ether), and the 4-methylpyrimidine is purified by distillation after the solvent has been removed, the purification preferably being carried out with the aid of fractional distillation ,
Mit Hilfe des erfindungsgemäßen Verfahrens ist es möglich, ausgehend von technisch verfügbaren Ausgangsmaterialien 4-Methylpyrimidin in technisch einfacher Weise mit guten Ausbeuten und hohen Reinheiten zu erhalten.With the aid of the process according to the invention, it is possible to obtain 4-methylpyrimidine in a technically simple manner with good yields and high purities, starting from industrially available starting materials.
Die nachfolgenden Beispiele sollen die vorliegende Erfindung näher veranschaulichen. The following examples are intended to illustrate the present invention in more detail.
BeispieleExamples
Beispiel 1 (Vergleich nach Bredereck et. al.)Example 1 (comparison according to Bredereck et. Al.)
200 g (1 ,5 mol) 4,4-Dimethoxy-2-butanon, 375 g (8,3 mol) Formamid, 25 g Ammoniumchlorid und 12,5 g Wasser wurden in einem Dreihalskolben mit Kolonne und Liebigkühler vorgelegt, innerhalb von 1 Stunde auf 185 °C (Badtemperatur) erhitzt und während 5 Stunden bei dieser Temperatur gehalten. Vom Kolonnenkopf destillierte während dieser Zeit bei einer Kopftemperatur von 50 bis 65 °C eine Flüssigkeit über, welche Methanol, Methylformiat und Ammoniak enthielt und mehrere Tage lang Kohlenmonoxid ausgaste.200 g (1.5 mol) of 4,4-dimethoxy-2-butanone, 375 g (8.3 mol) of formamide, 25 g of ammonium chloride and 12.5 g of water were placed in a three-necked flask with a column and Liebig condenser, within 1 Heated to 185 ° C (bath temperature) for an hour and held at this temperature for 5 hours. During this time, a liquid which contained methanol, methyl formate and ammonia and which outgassed carbon monoxide for several days distilled from the top of the column at a top temperature of 50 to 65 ° C.
Das zähflüssige Reaktionsprodukt wurde mit 500 ml Wasser und 65 gThe viscous reaction product was treated with 500 ml of water and 65 g
50 %iger Natronlauge versetzt und dann in einem Flüssig-Flüssig-Extraktor50% sodium hydroxide solution added and then in a liquid-liquid extractor
26 Stunden lang mit t-Butylmethylether extrahiert.Extracted with t-butyl methyl ether for 26 hours.
Der Extrakt wurde eingedampft und das Rohprodukt (71,5 g) über eine " Kolonne destilliert, wobei zwei Fraktionen gewonnen wurden:The extract was evaporated and the crude product distilled (71.5 g) over a "column wherein two fractions were obtained:
Kopftemperatur Auswaage Gehalt 4-MethylpyrimidinHead temperature scale content 4-methylpyrimidine
Fraktion 1 140 - 142°C 41,5 g 97,5 %Fraction 1 140 - 142 ° C 41.5 g 97.5%
Fraktion 2 142 - 144°C 8,5 g 88,3 %Fraction 2 142 - 144 ° C 8.5 g 88.3%
Insgesamt berechnete sich die isolierte Ausbeute zu 34,0 %.The total isolated yield was calculated to be 34.0%.
Beispiel 2 ferfindunσsσemäß)Example 2 ferfindunσsσemäß)
198,2 g (1,5 mol) 4,4-Dimethoxy-2-butanon wurden in einem Dreihalskolben mit Kolonne und Liebigkühler vorgelegt und auf 140 °C erhitzt. Hierzu wurden in 10 gleichen Portionen 141,9 g (1,36 mol) Formamidinacetat im Verlauf einer Stunde zugesetzt. Während dieser Zeit 03/010151198.2 g (1.5 mol) of 4,4-dimethoxy-2-butanone were placed in a three-necked flask with a column and Liebig condenser and heated to 140.degree. For this purpose, 141.9 g (1.36 mol) of formamidine acetate were added in 10 equal portions over the course of an hour. During this time 03/010151
sowie während der 4-stündigen Nachreaktionszeit bei 140 °C destillierte laufend reines Methanol ab.and during the 4-hour post-reaction time at 140 ° C, pure methanol continuously distilled off.
Der Ansatz wurde abgekühlt, mit 100 g Wasser und 65 g 50 %iger Natronlauge versetzt und insgesamt 20 Stunden kontinuierlich mit t-Butylmethylether extrahiert.The mixture was cooled, mixed with 100 g of water and 65 g of 50% sodium hydroxide solution and extracted continuously with t-butyl methyl ether for a total of 20 hours.
Der Extrakt wurde eingedampft und das Rohprodukt (101 ,8 g) über eine Kolonne destilliert, wobei zwei Fraktionen gewonnen wurden:The extract was evaporated and the crude product (101.8 g) was distilled through a column, two fractions being obtained:
Kopftemperatur Auswaage Gehalt 4-Methylpyrimidin Fraktion 1 140 - 142°C 68,5 g 96,1 %Head temperature Weight 4-methylpyrimidine fraction 1 140 - 142 ° C 68.5 g 96.1%
Fraktion 2 142 - 144°C 14,0 g 94,4 %Fraction 2 142 - 144 ° C 14.0 g 94.4%
Insgesamt berechnete sich die isolierte Ausbeute zu 61 ,8 %.The total isolated yield was calculated to be 61.8%.
Beispiel 3 ferfindunσsσemäß)Example 3 ferfindunσsσemäß)
208,2 g (2,0 mol) Formamidinacetat wurden in 100 g reiner Essigsäure suspendiert und auf 80 °C erwärmt. Innerhalb von 2 Stunden wurden 198,2 g (1,5 mol) 4,4-Dimethoxy-2-butanon bei 80 °C zudosiert und anschließend weitere 3 Stunden auf 150 °C (Badtemperatur) erhitzt. Während der gesamten Reaktonszeit wurde laufend entstehendes Methanol abdestilliert.208.2 g (2.0 mol) of formamidine acetate were suspended in 100 g of pure acetic acid and heated to 80 ° C. 198.2 g (1.5 mol) of 4,4-dimethoxy-2-butanone were metered in at 80 ° C. in the course of 2 hours and then heated to 150 ° C. (bath temperature) for a further 3 hours. The methanol formed was continuously distilled off during the entire reaction time.
Der Ansatz wurde abgekühlt, mit 300 g Wasser und 165,5 g 50 %iger Natronlauge versetzt und insgesamt 20 Stunden kontinuierlich mit t-Butylmethylether extrahiert.The mixture was cooled, 300 g of water and 165.5 g of 50% sodium hydroxide solution were added and the mixture was extracted continuously with t-butyl methyl ether for a total of 20 hours.
Der Extrakt wurde eingedampft und das Rohprodukt (90,3 g) über eine Kolonne destilliert. Hierbei wurden 72,8 g 4-Methylpyrimidin mit einem Gehalt von 95,3 % erhalten. Die Ausbeute lag bei 49,0 %. The extract was evaporated and the crude product (90.3 g) distilled through a column. This gave 72.8 g of 4-methylpyrimidine with a content of 95.3%. The yield was 49.0%.

Claims

Patentansprüche claims
1. Verfahren zur Herstellung von 4-Methylpyrimidin, dadurch gekennzeichnet, dass man ein 4,4-Dialkoxy-2-butanon mit einem Formamidinsalz ggf. in Gegenwart eines Löse- oder Verdünnungsmittels bei Temperaturen von 80 bis 180 °C umsetzt.1. A process for the preparation of 4-methylpyrimidine, characterized in that a 4,4-dialkoxy-2-butanone is reacted with a formamidine salt, if appropriate in the presence of a solvent or diluent, at from 80 to 180 ° C.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man als C4-Komponente 4,4-Dimethoxy-2-butanon verwendet.2. The method according to claim 1, characterized in that 4,4-dimethoxy-2-butanone is used as the C 4 component.
3. Verfahren nach den Ansprüchen 1 und 2, dadurch gekennzeichnet, dass man als Formamidinsalz Formamidinacetat einsetzt.3. Process according to claims 1 and 2, characterized in that formamidine acetate is used as the formamidine salt.
4. Verfahren nach den Ansprüchen 1 bis 3, dadurch gekennzeichnet, dass man die Umsetzung bei einer Temperatur von 110 bis 150 °C durchführt.4. The method according to claims 1 to 3, characterized in that one carries out the reaction at a temperature of 110 to 150 ° C.
5. Verfahren nach den Ansprüchen 1 bis 4, dadurch gekennzeichnet, dass man das Molverhältnis von 4,4-Dialkoxy-2-butanon zu Formamidinsalz auf 1 : 2 bis 2 : 1, insbesondere 1,2 : 1 bis 1 : 1,2, einstellt.5. The method according to claims 1 to 4, characterized in that the molar ratio of 4,4-dialkoxy-2-butanone to formamidine salt to 1: 2 to 2: 1, in particular 1.2: 1 to 1: 1.2 , sets.
6. Verfahren nach den Ansprüchen 1 bis 5, dadurch gekennzeichnet, dass man den während der Reaktion entstehenden Alkohol laufend abdestilliert.6. Process according to claims 1 to 5, characterized in that the alcohol formed during the reaction is continuously distilled off.
7. Verfahren nach den Ansprüchen 1 bis 6,dadurch gekennzeichnet, dass man nach erfolgter Umsetzung das Reaktionsgemisch mit Wasser und einer starken Base wie z. B. Natronlauge versetzt, das 4-Methylpyrimidin mit einem organischen Lösemittel extrahiert und anschließend durch Destillation reinigt.7. The method according to claims 1 to 6, characterized in that after the reaction, the reaction mixture with water and a strong base such as. B. sodium hydroxide solution, the 4-methylpyrimidine extracted with an organic solvent and then purified by distillation.
8. Verfahren nach Anspruch 7, dadurch gekennzeichnet, dass man die Reinigung des 4-Methylpyrimidins mit Hilfe einer fraktionierten Destillation durchführt. 8. The method according to claim 7, characterized in that one carries out the purification of the 4-methylpyrimidine with the aid of a fractional distillation.
PCT/EP2001/008614 2000-01-24 2001-07-25 Method for producing 4-methyl pyrimidine WO2003010151A1 (en)

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PCT/EP2001/008614 WO2003010151A1 (en) 2001-07-25 2001-07-25 Method for producing 4-methyl pyrimidine
US10/451,092 US6841672B2 (en) 2000-01-24 2001-07-25 Method for producing 4-methyl pyrimidine

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11439738B2 (en) 2007-11-29 2022-09-13 Fresenius Medical Care Holdings, Inc. Methods and Systems for fluid balancing in a dialysis system
US11525798B2 (en) 2012-12-21 2022-12-13 Fresenius Medical Care Holdings, Inc. Method and system of monitoring electrolyte levels and composition using capacitance or induction

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Publication number Priority date Publication date Assignee Title
DE822086C (en) * 1946-12-28 1951-11-22 Gen Aniline & Film Corp Process for the preparation of pyrimidines
SU91299A1 (en) * 1949-12-01 1975-07-30 The method of producing pyramidine derivatives
DE4308073A1 (en) * 1993-03-13 1994-09-15 Basf Ag Process for the preparation of 4-methylpyrimidines
DE10002835C1 (en) * 2000-01-24 2001-12-13 Sueddeutsche Kalkstickstoff Production of 4-methylpyridine, useful as an intermediate for pharmaceuticals and plant protection agents, comprises reacting a 4,4-dialkoxy-2-butanone with a formamidine salt

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE822086C (en) * 1946-12-28 1951-11-22 Gen Aniline & Film Corp Process for the preparation of pyrimidines
SU91299A1 (en) * 1949-12-01 1975-07-30 The method of producing pyramidine derivatives
DE4308073A1 (en) * 1993-03-13 1994-09-15 Basf Ag Process for the preparation of 4-methylpyrimidines
DE10002835C1 (en) * 2000-01-24 2001-12-13 Sueddeutsche Kalkstickstoff Production of 4-methylpyridine, useful as an intermediate for pharmaceuticals and plant protection agents, comprises reacting a 4,4-dialkoxy-2-butanone with a formamidine salt

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Title
CHEMICAL ABSTRACTS, vol. 83, no. 28, 1975, Columbus, Ohio, US; abstract no. 193373u, page 475; column 1; XP002192110 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11439738B2 (en) 2007-11-29 2022-09-13 Fresenius Medical Care Holdings, Inc. Methods and Systems for fluid balancing in a dialysis system
US11525798B2 (en) 2012-12-21 2022-12-13 Fresenius Medical Care Holdings, Inc. Method and system of monitoring electrolyte levels and composition using capacitance or induction

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