EP1204647A1 - Method for the production of 4,6-dichloropyrimidine with the aid of phosgene - Google Patents

Method for the production of 4,6-dichloropyrimidine with the aid of phosgene

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Publication number
EP1204647A1
EP1204647A1 EP00951392A EP00951392A EP1204647A1 EP 1204647 A1 EP1204647 A1 EP 1204647A1 EP 00951392 A EP00951392 A EP 00951392A EP 00951392 A EP00951392 A EP 00951392A EP 1204647 A1 EP1204647 A1 EP 1204647A1
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EP
European Patent Office
Prior art keywords
chloro
phosgene
methoxypyrimidine
nitrogen
process according
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EP00951392A
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German (de)
French (fr)
Inventor
Franz-Josef Mais
Günther Cramm
Alexander Klausener
Guido Steffan
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Bayer Chemicals AG
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D237/12—Halogen atoms or nitro radicals

Definitions

  • the present invention relates to a process for the preparation of 4,6-dichloropyrimidine from 4-chloro-6-methoxypyrimidine.
  • 4,6-dichloropyrimidine is a valuable one
  • the process according to the invention can be carried out in a solvent (for details see below) or in the melt.
  • the execution in one is preferred
  • nitrogen-containing auxiliaries are nitrogen-containing bases, for example amines of the formula R * R 2 R 3 N (in which R 1 , R 2 and R 3 independently of one another are each for C 1 -C 10 alkyl, C 1 -C 4 aryl, C 5 -C9 heteroaryl with 1 to 3
  • Heteroatoms from the group N, O and S or C 6 -C 10 aryl -CC-C 6 alkyl mean can) or unsaturated or saturated cyclic amines having 1 to 2 nitrogen atoms and 5 to 11 carbon atoms, where the cyclic amines can optionally be substituted 1 to 3 times by C ⁇ -C ⁇ o-alkyl.
  • Examples of such amines are: triethylamine, N, N-diethylaniline, N, N-dimethylaniline, diisopropylethylamine, 4- (N, N-dimethylamino) pyridine (DMAP), with C 1 -C 2 -alkylmono- or -dialkylated pyridines , Mo holin, imidazole, triazole, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), l, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) and piperidine.
  • Amides and ureas which can also be used as solvents can also be used as nitrogen-containing auxiliaries. Examples are: N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone,
  • Tetramethyl urea and cyclic ureas such as 1,3-dimethyimidazolidin-2-one (DMEU) and 1,3-dimethyltetrahydro-2 (1H) pyrimidinone (DMPH).
  • DMEU 1,3-dimethyimidazolidin-2-one
  • DMPH 1,3-dimethyltetrahydro-2 (1H) pyrimidinone
  • the amount of nitrogen-containing auxiliaries can be varied within a wide range. Smaller amounts, for example those of less than 1 mole per mole of 4-chloro-6-methoxypyrimidine, can be used, for example, if one wants to use the nitrogen-containing auxiliary as a catalyst. Higher amounts, for example those of more than 1.5 moles per mole of 4-chloro-6-methoxypyrimidine, can be used if one wishes to use the nitrogen-containing auxiliary both as a catalyst and as a solvent.
  • the amount of nitrogen-containing auxiliary can be between 0.001 and 25 mol, preferably between 0.01 and 15
  • Mol are based on 4-chloro-6-methoxypyrimidine. Amounts in the range from 0.01 to 0.5 mole per mole of 4-chloro-6-methoxypyrimidine are particularly preferred when the nitrogen-containing auxiliary is used as a catalyst.
  • Solvents are basically those that are not suitable for the reaction to be carried out influence negatively. Examples are aliphatic solvents such as alkanes, cycloalkanes and haloalkanes, aromatic solvents such as benzene, xylenes, toluene, chlorobenzenes, benzotrifluorides, p-chlorobenzotrifluoride and anisole, where the aliphatic and aromatic solvents can optionally be further substituted, nitriles such as acetonitrile and benzonitrile, N- containing solvents such as
  • the method according to the invention can e.g. at temperatures in the range from 0 to 200 ° C., preferably from 20 to 150 ° C., particularly preferably from 40 to 120 ° C.
  • the pressure is not critical.
  • Working at normal pressure is particularly preferred.
  • the process according to the invention can be carried out in various embodiments, for example batchwise, batchwise in batches, partially continuously or continuously.
  • a possible procedure is as follows: 4-chloro-6-methoxypyrimidine is initially introduced with a nitrogenous auxiliary, optionally together with a solvent, and gaseous phosgene is introduced.
  • Another variant is to add the phosgene in liquid form or dissolved in a solvent.
  • the entire phosgene can be added directly at the start of the reaction or dosed over a certain period of time.
  • the reaction mixture present after the reaction can be worked up, for example, by first removing excess phosgene from the batch by blowing and / or distilling and distilling the remaining reaction mixture. If water-soluble auxiliaries were used, it is expedient to first add water to the reaction mixture and to distill or recrystallize the remaining product after the auxiliaries have been washed out and after the solvent has been distilled off.
  • a further, generally advantageous variant consists in working up by extraction.
  • nitrogenous auxiliary in the simplest case N, N-dimethylformamide as nitrogenous auxiliary and xylene as solvent
  • the reaction mixture separates into two phases.
  • the xylene phase containing 4,6-dichloropyrimidine can then be separated off and the N, N-dimethylformamide phase can be extracted one or more times with xylene.
  • the combined xylene phases can then be distilled.
  • reaction according to the invention can also be carried out only in the presence of a nitrogen-containing auxiliary and then the reaction mixture formed can be extracted with a suitable solvent, for example aliphatic or aromatic hydrocarbons such as hexane, isooctane, methylcyclohexane, toluene, xylene, decalin, tetralin or hydrocarbon mixtures.
  • a suitable solvent for example aliphatic or aromatic hydrocarbons such as hexane, isooctane, methylcyclohexane, toluene, xylene, decalin, tetralin or hydrocarbon mixtures.
  • the process according to the invention allows the preparation of 4,6-dichloropyrimidine in a simple manner and in good yields and without the use of phosphorus-containing chlorinating agents.
  • HPLC contents were 15.57% of 4,6-dichloropyrimidine in the xylene phase and 5.38% in the N, N-dimethylformamide phase. This corresponds to yields of 63.45%
  • the upper phase contained 0.22% 4-chloro-6-hydroxypyrimidine

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

4,6-dichloropyrimidine is advantageously produced from 4-chloro-6-methoxypyrimidine by using phosgene as chlorinating agent and working in the presence of nitrogen-containing auxiliary agents.

Description

Verfahren zur Herstellung von 4,6-Dichlorpyrimidin mit PhosgenProcess for the preparation of 4,6-dichloropyrimidine with phosgene
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von 4,6-Dichlor- pyrimidin aus 4-Chlor-6-methoxypyrimidin. 4,6-Dichlorpyrimidin ist ein wertvollesThe present invention relates to a process for the preparation of 4,6-dichloropyrimidine from 4-chloro-6-methoxypyrimidine. 4,6-dichloropyrimidine is a valuable one
Zwischenprodukt zur Herstellung von Planzenschutzmitteln.Intermediate product for the production of crop protection agents.
Es sind eine Reihe Verfahren zur Herstellung von 4,6-Dichlorpyrimidin bekannt, siehe beispielsweise WO96/23776, EP-A-697 406, EP-A-745 593, WO 95/29166, DE-A-19 53 129 und GB 2 325 224. Bei diesen Verfahren wird jedoch immer vonA number of processes are known for the preparation of 4,6-dichloropyrimidine, see for example WO96 / 23776, EP-A-697 406, EP-A-745 593, WO 95/29166, DE-A-19 53 129 and GB 2 325 224. However, these procedures always use
4,6-Dihydroxypyrimidin ausgegangen.4,6-Dihydroxypyrimidine assumed.
Es ist auch bekannt (siehe Res. Discl. n 391, 690-691 (1996)), daß man 4,6-Dichlor- pyrimidin durch Umsetzung von 4-Chlor-6-methoxypyrirnidin mit einem Chlorier- agenz der Formel R3PCI2 umsetzen kann. Das Chlorierungsreagenz kann als solches eingesetzt oder in situ aus einer Verbindung der Formel R3P=O und Phosgen hergestellt werden. Diese Literaturstelle legt nahe, daß 4-Chlor-6-methoxypyrimidin mit Phosgen alleine nicht in der gewünschten Weise reagiert.It is also known (see Res. Discl. N 391, 690-691 (1996)) that 4,6-dichloropyrimidine can be reacted with a chlorinating agent of the formula R3PCI2 by reacting 4-chloro-6-methoxypyrirnidine , The chlorination reagent can be used as such or can be prepared in situ from a compound of the formula R3P = O and phosgene. This literature suggests that 4-chloro-6-methoxypyrimidine does not react in the desired manner with phosgene alone.
Es wurde nun ein Verfahren zur Herstellung von 4,6-Dichlorpyrimidin gefunden, das dadurch gekennzeichnet ist, daß man 4-Chlor-6-methoxypyrirnidin mit Phosgen als Chlorierungsmittel in Gegenwart von stickstoffhaltigen Hilfsstoffen umsetzt.A process for the preparation of 4,6-dichloropyrimidine has now been found, which is characterized in that 4-chloro-6-methoxypyrirnidine is reacted with phosgene as the chlorinating agent in the presence of nitrogen-containing auxiliaries.
Das erfindungsgemäße Verfahren kann in einem Lösungsmittel (Details siehe unten) oder in der Schmelze durchgeführt werden. Bevorzugt ist die Ausführung in einemThe process according to the invention can be carried out in a solvent (for details see below) or in the melt. The execution in one is preferred
Lösungsmittel.Solvent.
Als stickstoffhaltige Hilfsstoffe kommen z.B. stickstoffhaltige Basen in Frage, beispielsweise Amine der Formel R*R2R3N (worin R1, R2 und R3 unabhängig voneinander jeweils für Cι-C10-Alkyl, Cö-C^-Aryl, C5-C9-Heteroaryl mit 1 bis 3Examples of suitable nitrogen-containing auxiliaries are nitrogen-containing bases, for example amines of the formula R * R 2 R 3 N (in which R 1 , R 2 and R 3 independently of one another are each for C 1 -C 10 alkyl, C 1 -C 4 aryl, C 5 -C9 heteroaryl with 1 to 3
Heteroatomen aus der Gruppe N, O und S oder C6-C10-Aryl-Cι-C6-alkyl bedeuten können) oder ungesättigte oder gesättigte cyclische Amine mit 1 bis 2 Stickstoffatomen und 5 bis 11 Kohlenstoffatomen, wobei die cyclischen Amine gegebenenfalls 1- bis 3-fach durch Cι-Cιo-Alkyl substituiert sein können. Beispiele für solche Amine sind: Triethylamin, N,N-Diethylanilin, N,N-Dimethylanilin, Diiso- propylethylamin, 4-(N,N-dimethylamino)-pyridin (DMAP), mit Cι-C2-Alkylmono- oder -dialkylierte Pyridine, Mo holin, Imidazol, Triazol, 1,5-Diazabi- cyclo[4.3.0]non-5-en (DBN), l,8-Diazabicyclo[5.4.0]undec-7-en (DBU) und Piperidin. Weiterhin können als stickstoffhaltige Hilfsstoffe Amide und Harnstoffe eingesetzt werden, die auch als Lösungsmittel verwendet werden können. Beispiele sind: N,N-Dimethylformamid, N,N-Dimethylacetamid, N-Methylpyrrolidon,Heteroatoms from the group N, O and S or C 6 -C 10 aryl -CC-C 6 alkyl mean can) or unsaturated or saturated cyclic amines having 1 to 2 nitrogen atoms and 5 to 11 carbon atoms, where the cyclic amines can optionally be substituted 1 to 3 times by Cι-Cιo-alkyl. Examples of such amines are: triethylamine, N, N-diethylaniline, N, N-dimethylaniline, diisopropylethylamine, 4- (N, N-dimethylamino) pyridine (DMAP), with C 1 -C 2 -alkylmono- or -dialkylated pyridines , Mo holin, imidazole, triazole, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), l, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) and piperidine. Amides and ureas which can also be used as solvents can also be used as nitrogen-containing auxiliaries. Examples are: N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone,
Tetramethylharnstoff und cyclische Harnstoffe wie l,3-Dimethyimidazolidin-2-on (DMEU) und l,3-Dimethyltetrahydro-2(lH)-pyrimidinon (DMPH).Tetramethyl urea and cyclic ureas such as 1,3-dimethyimidazolidin-2-one (DMEU) and 1,3-dimethyltetrahydro-2 (1H) pyrimidinone (DMPH).
In das erfindungsgemäße Verfahren setzt man im allgemeinen mindestens 1 Mol Phosgen pro Mol 4-Chlor-6-methoxypyrimidin ein. Vorzugsweise beträgt dieseIn general, at least 1 mole of phosgene per mole of 4-chloro-6-methoxypyrimidine is used in the process according to the invention. This is preferably
Menge 1,05 bis 20 Mol, besonders bevorzugt 1,1 bis 10 Mol.Amount 1.05 to 20 mol, particularly preferably 1.1 to 10 mol.
Die Menge der stickstoffhaltigen Hilfsstoffe kann in einem weiten Bereich variiert werden. Geringere Mengen, beispielsweise solche von unter 1 Mol pro Mol 4-Chlor- 6-methoxypyrimidin kann man beispielsweise einsetzen, wenn man den stickstoffhaltigen Hilfsstoff als Katalysator anwenden will. Höhere Mengen, beispielsweise solche von mehr als 1,5 Mol pro Mol 4-Chlor-6-methoxypyrimidin kann man einsetzen, wenn man den stickstoffhaltigen Hilfsstoff sowohl als Katalysator als auch als Lösungsmittel einsetzen möchte. Beispielsweise kann die Menge an stickstoff- haltigem Hilfsstoff zwischen 0,001 und 25 Mol, bevorzugt zwischen 0,01 und 15The amount of nitrogen-containing auxiliaries can be varied within a wide range. Smaller amounts, for example those of less than 1 mole per mole of 4-chloro-6-methoxypyrimidine, can be used, for example, if one wants to use the nitrogen-containing auxiliary as a catalyst. Higher amounts, for example those of more than 1.5 moles per mole of 4-chloro-6-methoxypyrimidine, can be used if one wishes to use the nitrogen-containing auxiliary both as a catalyst and as a solvent. For example, the amount of nitrogen-containing auxiliary can be between 0.001 and 25 mol, preferably between 0.01 and 15
Mol liegen, jeweils bezogen auf 4-Chlor-6-methoxypyrimidin. Besonders bevorzugt beim Einsatz des stickstoffhaltigen Hilfsstoffs als Katalysator sind Mengen im Bereich von 0,01 bis 0,5 Mol pro Mol 4-Chlor-6-methoxypyrimidin.Mol are based on 4-chloro-6-methoxypyrimidine. Amounts in the range from 0.01 to 0.5 mole per mole of 4-chloro-6-methoxypyrimidine are particularly preferred when the nitrogen-containing auxiliary is used as a catalyst.
Wenn man in Gegenwart von Lösungsmitteln arbeiten möchte kommen alsIf you want to work in the presence of solvents come as
Lösungsmittel grundsätzlich solche in Frage, die die durchzuführende Reaktion nicht negativ beeinflussen. Beispiele sind aliphatische Lösungsmittel wie Alkane, Cycloalkane und Halogenalkane, aromatische Lösungsmittel wie Benzol, Xylole, Toluol, Chlorbenzole, Benzotrifluoride, p-Chlorbenzotrifluorid und Anisol, wobei die aliphatischen und aromatischen Lösungsmittel gegebenenfalls weiter substituiert sein können, Nitrile wie Acetonitril und Benzonitril, N-haltige Lösungsmittel wieSolvents are basically those that are not suitable for the reaction to be carried out influence negatively. Examples are aliphatic solvents such as alkanes, cycloalkanes and haloalkanes, aromatic solvents such as benzene, xylenes, toluene, chlorobenzenes, benzotrifluorides, p-chlorobenzotrifluoride and anisole, where the aliphatic and aromatic solvents can optionally be further substituted, nitriles such as acetonitrile and benzonitrile, N- containing solvents such as
N,N-Dimethylformamid, N,N-Dimethylacetamid, Lactame und cyclische Harnstoffe und Ether und Polyether der verschiedensten Art.N, N-dimethylformamide, N, N-dimethylacetamide, lactams and cyclic ureas and ethers and polyethers of all kinds.
Das erfindungsgemäße Verfahren kann man z.B. bei Temperaturen im Bereich 0 bis 200°C, bevorzugt bei 20 bis 150°C, besonders bevorzugt bei 40 bis 120°C, durchführen. Der Druck ist nicht kritisch. Man kann beispielsweise bei 0,1 bis 50 bar, bevorzugt bei 0,5 bis 5 bar, arbeiten. Besonders bevorzugt arbeitet man bei Normaldruck.The method according to the invention can e.g. at temperatures in the range from 0 to 200 ° C., preferably from 20 to 150 ° C., particularly preferably from 40 to 120 ° C. The pressure is not critical. One can, for example, work at 0.1 to 50 bar, preferably at 0.5 to 5 bar. Working at normal pressure is particularly preferred.
Das erfindungsgemäße Verfahren kann in verschiedenen Ausführungsformen durchgeführt werden, beispielsweise diskontinuierlich, diskontinuierlich in Schüben, teilkontinuierlich oder kontinuierlich. Eine mögliche Verfahrensweise ist wie folgt: Man legt 4-Chlor-6-methoxypyrimidin mit einem stickstoffhaltigen Hilfsstoff, gegebenenfalls zusammen mit einem Lösungsmittel vor und leitet gasförmiges Phosgen ein.The process according to the invention can be carried out in various embodiments, for example batchwise, batchwise in batches, partially continuously or continuously. A possible procedure is as follows: 4-chloro-6-methoxypyrimidine is initially introduced with a nitrogenous auxiliary, optionally together with a solvent, and gaseous phosgene is introduced.
Eine andere Variante besteht darin, das Phosgen in flüssiger Form oder gelöst in einem Lösungsmittel zuzugeben. Dabei kann man das gesamte Phosgen direkt am Anfang der Umsetzung zugeben oder es über einen gewissen Zeitraum verteilt dosieren.Another variant is to add the phosgene in liquid form or dissolved in a solvent. The entire phosgene can be added directly at the start of the reaction or dosed over a certain period of time.
Die Aufarbeitung des nach der Reaktion vorliegenden Reaktionsgemisches kann beispielsweise erfolgen, indem man zunächst überschüssiges Phosgen aus dem Ansatz durch Ausblasen und/oder Andestillieren entfernt und das zurückbleibende Reaktionsgemisch destilliert. Falls wasserlösliche Hilfsstoffe eingesetzt wurden ist es günstig, das Reaktionsgemisch zunächst mit Wasser zu versetzen und nach dem Auswaschen der Hilfsstoffe und nach der AbdestiUation des Lösungsmittels das zurückbleibende Produkt zu destillieren oder umzukristallisieren.The reaction mixture present after the reaction can be worked up, for example, by first removing excess phosgene from the batch by blowing and / or distilling and distilling the remaining reaction mixture. If water-soluble auxiliaries were used, it is expedient to first add water to the reaction mixture and to distill or recrystallize the remaining product after the auxiliaries have been washed out and after the solvent has been distilled off.
Eine weitere, im allgemeinen vorteilhafte Variante besteht in der Aufarbeitung durch Extraktion. Bei geeigneter Wahl der Kombination von stickstoffhaltigem Hilfsstoff mit dem Lösungsmittel, im einfachsten Fall N,N-Dimethylformamid als stickstoffhaltiger Hilfsstoff und Xylol als Lösungsmittel, trennt sich das Reaktionsgemisch in zwei Phasen. Die 4,6-Dichlorpyrimidin enthaltende Xylolphase kann dann abgetrennt und die N,N-Dimethylformamid-Phase noch ein- oder mehrfach mit Xylol extrahiert werden. Die vereinigten Xylolphasen können dann destilliert werden.A further, generally advantageous variant consists in working up by extraction. With a suitable choice of the combination of nitrogenous auxiliary with the solvent, in the simplest case N, N-dimethylformamide as nitrogenous auxiliary and xylene as solvent, the reaction mixture separates into two phases. The xylene phase containing 4,6-dichloropyrimidine can then be separated off and the N, N-dimethylformamide phase can be extracted one or more times with xylene. The combined xylene phases can then be distilled.
Man kann auch die erfindungsgemäße Umsetzung nur in Gegenwart eines stick- stoffhaltigen Hilfsstoffes durchführen und dann das entstehende Reaktionsgemisch mit einem geeigneten Lösungsmittel, beispielsweise aliphatischen oder aromatischen Kohlenwasserstoffen wie Hexan, Isooctan, Methylcyclohexan, Toluol, Xylol, Decalin, Tetralin oder Kohlenwasserstoffgemischen extrahieren.The reaction according to the invention can also be carried out only in the presence of a nitrogen-containing auxiliary and then the reaction mixture formed can be extracted with a suitable solvent, for example aliphatic or aromatic hydrocarbons such as hexane, isooctane, methylcyclohexane, toluene, xylene, decalin, tetralin or hydrocarbon mixtures.
Das erfindungsgemäße Verfahren ist im Hinblick auf die Literaturstelle Res. Discl. a.a.O. ausgesprochen überraschend. Dort wird zwar Phosgen als Chlorierungsmittel erwähnt, aber nur zur in-situ-Erzeugung von Triorgano-di-chlorphosphoran. Eine direkte Umsetzung von 4-Chlor-6-methoxypyrimidin mit Phosgen wird nicht erwähnt.With regard to the literature reference Res. Discl. ibid extremely surprising. Phosgene is mentioned there as a chlorinating agent, but only for the in situ production of triorgano-di-chlorophosphorane. A direct reaction of 4-chloro-6-methoxypyrimidine with phosgene is not mentioned.
Das erfindungsgemäße Verfahren gestattet die Herstellung von 4,6-Dichlorpyrimidin in einfacher Weise und in guten Ausbeuten und ohne die Verwendung von phosphorhaltigen Chlorierungsmitteln. BeispieleThe process according to the invention allows the preparation of 4,6-dichloropyrimidine in a simple manner and in good yields and without the use of phosphorus-containing chlorinating agents. Examples
Beispiel 1example 1
In einem Rührgefäß wurden 14,5 g 4-Chlor-6-methoxypyrimidin und eine Mischung aus 75 ml N,N-Dimethylformamid und 75 ml Xylol zusammengegeben, unter Rühren auf 130 bis 135°C erhitzt und dann im Verlaufe von 3 Stunden mit 99,9 g Phosgen gleichmäßig schnell begast. Danach wurden 3,5 Stunden mit Stickstoff Phosgenreste ausgeblasen. Nach dem Abkühlen erhielt man 159,7 g eines zwei- phasigen Reaktionsgemisches. Nach der Phasentrennung lagen 60,8 g obere, klareIn a stirred vessel, 14.5 g of 4-chloro-6-methoxypyrimidine and a mixture of 75 ml of N, N-dimethylformamide and 75 ml of xylene were combined, heated to 130 to 135 ° C. with stirring and then at 99 in the course of 3 hours , 9 g phosgene fumigated equally quickly. Thereafter, phosgene residues were blown out with nitrogen for 3.5 hours. After cooling, 159.7 g of a two-phase reaction mixture were obtained. After phase separation, there were 60.8 g of clear top
Xylolphase und 90,7 g schwarze untere N,N-Dimethylformamid-Phase vor (Rest: Verlust bei der Phasentrennung).Xylene phase and 90.7 g of black lower N, N-dimethylformamide phase before (rest: loss in phase separation).
Die HPLC-Gehalte betrugen 15,57 % an 4,6-Dichlorpyrimidin in der Xylolphase und 5,38 % in der N,N-Dimethylformamid-Phase. Das entspricht Ausbeuten von 63,45 %The HPLC contents were 15.57% of 4,6-dichloropyrimidine in the xylene phase and 5.38% in the N, N-dimethylformamide phase. This corresponds to yields of 63.45%
4,6-Dichloφyrimidin in der Xylolphase und 32,75 % in der N,N-Dimethylformamid- Phase, d.h. insgesamt 96,3 % 4,6-Dichlorpyrimidin. 4-Chlor-6-methoxypyrimidin ist in beiden Phasen nicht nachweisbar gewesen.4,6-dichloropyrimidine in the xylene phase and 32.75% in the N, N-dimethylformamide phase, i.e. a total of 96.3% 4,6-dichloropyrimidine. 4-Chloro-6-methoxypyrimidine was undetectable in both phases.
Beispiel 2Example 2
In einem Rührgefäß wurden 21,68 g 4-Chlor-6-methoxypyrimidin, 129 g Xylol und 36,35 g N,N-Dimethylanilin zusammengegeben und unter Rühren auf 105°C erhitzt. Bei dieser Temperatur wurden im Verlaufe von 3,5 Stunden 76 g Phosgen gleich- mäßig schnell eingeleitet. Danach wurde überschüssiges Phosgen mit Stickstoff ausgeblasen. Nach dem Abkühlen erhielt man ein zweiphasiges Gemisch. Die Auswaage an oberer, xylolreicher Phase betrug 135,12 g, die untere, N,N-dimethylanilinreiche Phase wog 37,1 g.21.68 g of 4-chloro-6-methoxypyrimidine, 129 g of xylene and 36.35 g of N, N-dimethylaniline were combined in a stirred vessel and heated to 105 ° C. with stirring. At this temperature, 76 g of phosgene were introduced uniformly quickly over the course of 3.5 hours. Excess phosgene was then blown out with nitrogen. After cooling, a two-phase mixture was obtained. The weight of the upper, xylene-rich phase was 135.12 g, the lower, N, N-dimethylaniline-rich phase weighed 37.1 g.
Nach HPLC-Analyse enthielt die obere Phase 0,22 % 4-Chlor-6-hydroxypyrimidin,According to HPLC analysis, the upper phase contained 0.22% 4-chloro-6-hydroxypyrimidine,
0,66 % 4-Chlor-6-methoxypyrimidin und 13,05 % 4,6-Dichloφyrimidin. Die untere Phase enthielt 0,5 % 4-Chlor-6-hydroxypyrimidin und 5,6 % 4,6-Dichlθφyrimidin. Das entspricht einer Ausbeute an 4,6-Dichloφyrimidin von 88,2 % bezogen auf eingesetztes 4-Chlor-6-methoxypyrimidin. 0.66% 4-chloro-6-methoxypyrimidine and 13.05% 4,6-dichloφyrimidine. The lower one Phase contained 0.5% 4-chloro-6-hydroxypyrimidine and 5.6% 4,6-dichlorotyrimidine. This corresponds to a yield of 4,6-dichloropyrimidine of 88.2% based on the 4-chloro-6-methoxypyrimidine used.

Claims

Patentansprtiche Patentansprtiche
1. Verfahren zur Herstellung von 4,6-Dichloφyrimidin, dadurch gekennzeichnet, daß man 4-Chlor-6-rnethoxypyrimidin mit Phosgen als Chlorie- rungsmittel in Gegenwart von stickstoffhaltigen Hilfsstoffen umsetzt.1. A process for the preparation of 4,6-dichloφyrimidine, characterized in that 4-chloro-6-rnethoxypyrimidine is reacted with phosgene as the chlorinating agent in the presence of nitrogen-containing auxiliaries.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man als stickstoffhaltige Hilfsstoffe Amine der Formel R1R R3N (worin R1, R2 und R3 unabhängig voneinander jeweils für Cι-Cιo-Alkyl, Cö-CiQ-Aryl, C5-C9- Heteroaryl mit 1 bis 3 Heteroatomen aus der Gruppe N, O und S oder bedeuten können) oder ungesättigte oder gesättigte cyclische Amine mit 1 bis 2 Stickstoffatomen und 5 bis 11 Kohlenstoffatomen oder Amide oder Harnstoffe einsetzt.2. The method according to claim 1, characterized in that as nitrogen-containing adjuvants amines of the formula R 1 RR 3 N (wherein R 1, R 2 and R 3 are each independently Cι-Cιo-alkyl, Ci Q-Coe aryl, C5-C9 heteroaryl with 1 to 3 heteroatoms from the group N, O and S or can mean) or unsaturated or saturated cyclic amines having 1 to 2 nitrogen atoms and 5 to 11 carbon atoms or amides or ureas.
3. Verfahren nach Ansprüchen 1 und 2, dadurch gekennzeichnet, daß man mindestens 1 Mol Phosgen pro Mol 4-Chlor-6-methoxypyrimidin einsetzt.3. Process according to Claims 1 and 2, characterized in that at least 1 mole of phosgene is used per mole of 4-chloro-6-methoxypyrimidine.
4. Verfahren nach Ansprüchen 1 bis 3, dadurch gekennzeichnet, daß das Molverhältnis von Phosgen zu 4-Chlor-6-methoxypyrimidin 1,05:1 bis 20:1 beträgt.4. Process according to Claims 1 to 3, characterized in that the molar ratio of phosgene to 4-chloro-6-methoxypyrimidine is 1.05: 1 to 20: 1.
5. Verfahren nach Ansprüchen 1 bis 4, dadurch gekennzeichnet, daß man pro Mol 4-Chlor-6-methoxypyrimidin 0,001 bis 25 Mol stickstoffhaltigen Hilfsstoff einsetzt.5. Process according to Claims 1 to 4, characterized in that 0.001 to 25 moles of nitrogenous auxiliary are used per mole of 4-chloro-6-methoxypyrimidine.
6. Verfahren nach Ansprüchen 1 bis 5, dadurch gekennzeichnet, daß man es in Gegenwart eines Lösungsmittels durchführt.6. Process according to Claims 1 to 5, characterized in that it is carried out in the presence of a solvent.
7. Verfahren nach Anspruch 6, dadurch gekennzeichnet, daß man es in Gegen- wart aliphatischer Lösungsmittel, aromatischer Lösungsmittel, Nitrile,7. The method according to claim 6, characterized in that it is present in the presence of aliphatic solvents, aromatic solvents, nitriles,
N-haltiger Lösungsmittel, Einern oder Polyethern durchführt. Verfahren nach Ansprüchen 1 bis 7, dadurch gekennzeichnet, daß man es bei Temperaturen im Bereich 0 bis 200°C und Drucken im Bereich 0,1 bis 50 bar durchführt. N-containing solvents, ones or polyethers. Process according to Claims 1 to 7, characterized in that it is carried out at temperatures in the range from 0 to 200 ° C and pressures in the range from 0.1 to 50 bar.
EP00951392A 1999-07-28 2000-07-17 Method for the production of 4,6-dichloropyrimidine with the aid of phosgene Withdrawn EP1204647A1 (en)

Applications Claiming Priority (3)

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DE19935322 1999-07-28
DE19935322A DE19935322A1 (en) 1999-07-28 1999-07-28 Process for the preparation of 4,6-dichloropyrimidine with phosgene
PCT/EP2000/006805 WO2001009105A1 (en) 1999-07-28 2000-07-17 Method for the production of 4,6-dichloropyrimidine with the aid of phosgene

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US20020042514A1 (en) * 2000-06-26 2002-04-11 Doyle Timothy John Synthesis of chlorinated pyrimidines
US6982331B2 (en) * 2001-06-08 2006-01-03 Syngenta Crop Protection, Inc. Synthesis of chlorinated pyrimidines
US6753367B2 (en) * 2001-08-20 2004-06-22 General Electric Company Flame retardant polycarbonate compositions with improved weathering performance containing cyanoacrylic esters
CN106053691A (en) * 2016-07-19 2016-10-26 安徽广信农化股份有限公司 Method for measuring content of 4,6-dichloropyrimidine

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GB9408270D0 (en) 1994-04-26 1994-06-15 Zeneca Ltd Chemical process
DE4429466A1 (en) * 1994-08-19 1996-02-22 Bayer Ag Process for the preparation of polychloropyrimidines
US6018045A (en) 1995-01-30 2000-01-25 Zeneca Limited Process for preparing 4,6-dichloro-pyrimidine
AT402818B (en) 1995-06-02 1997-09-25 Chemie Linz Gmbh METHOD FOR PRODUCING PURE 4,6-DICHLORPYRIMIDINE
DE19531299A1 (en) 1995-08-25 1997-02-27 Bayer Ag Process for the preparation of 4,6-dichloropyrimidines
GB9709810D0 (en) * 1997-05-14 1997-07-09 Zeneca Ltd Chemical process

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