DE1770774A1 - Process for the preparation of halopyrimidines - Google Patents

Description

Process for the preparation of halopyrimidines halopyrimidines are known from the literature. In the above-described process for their preparation the synthesis generally takes place over several stages, the last stage being a chlorination of the heterocyclic ring is carried out.

It has now been found that halopyrimidines can be prepared in a new and very simple manner in one process step if nitriles of the general formula are used with isocyanide dichlorides of the general formula implements; In the general formulas (I) and (II), R denotes hydrogen, fluorine, chlorine, bromine, nitro, alkyl, aralkyl, cycloalkyl, aryl, itril, alkoxy, acyloxy, carbalkoxy , Acyl, such as arylsulfonyl or alkylsulfonyl substituents, R1 and R2 independently of one another hydrogen, fluorine, chlorine or bromine subotituents, R3 hydrogen, fluorine, chlorine, bromine, alkyl, aralkyl, cycloalkyl, Aryl or aromatic-heterocyclic radicals, R4 and R5 independently of one another are hydrogen, fluorine, chlorine or bromine substituents, where at least two of the radicals R to R5 are fluorine, bromine or preferably chlorine substituents, and the alkyl, aralkyl -, aryl and hetero radicals can have further substituents, such as halo (for example C1, Br or P), cyano, nitro groups.

The starting components (I) and (II) are approximately stoichiometric Xengeny proportions or with an excess of one or the other component together unset.

Nitriles of formula (I) suitable for the process are e.g.

Acetonitrile, chloroacetonitrile, dichloroacetonitrile, trichloroacetonitrile, Bromoacetonitrile, dibromoacetonitrile, eribromoacetonitrile, nitroacetonitrile, dichloro-nitro-acetonitrile, Dibromonitro-acetonitrile, propionitrile, # -chloropropionitrile, butyronitrile, #, γ-dichlorobutyronitrile, α-methyl-α -chlorobutyronitrile, palmitonitrile, ethoxy-dichloroacetonitrile, Maodinitrile, methoxyacetonitrile, acetoxyacetonitrile, α-methazypropionitrile, Acetylacetonitrile, benzyl cyanide, o-chlorobenzyl cyanide, phenylchloro-acetonitrile, phenyl-dichloro-scetonitrile, p-Bromobenzyl cyanide, o-Ritrobenzyloyanid, -Naphtbylaoetcitril, (p-Toluylsulfonyl) -propionäurenitril, , α-sulfonylactonitriles, such as methylsulfonyl or ethylsulfonylacetonitrile.

Of course, dinitriles, for example adipic dinitrile, are used in the reaction, Isocyanide dichlorides suitable for the process of formula (II) are e.g. chloromethyl isocyanide dichloride, trichloromethyl isooyanide dichloride, Pentachloroethyl isocyanide dichloride, methyl isocyanide dichloride, Dodecyl isocyanide dichloride, 3enzyl irocyanide dichloride, substituted benzyl isocyanide dichlorides, such as 3, 4-dichlorobenzyl isocyanide dichloride and 1 ', 1'-dichlorobenzyl isocyanide dichloride.

The process of the invention is carried out in the presence or in the absence inert solvent or diluent, conveniently at temperatures between 200 and 6000C performed; the reaction is preferred at temperatures between 1500 and 3500C carried out, with pressureless or under pressure and optionally can be worked in the gas phase. In general it is advantageous to use the starting components to be heated together in stoichiometric amounts, or one of the components or a halopyrimidine which may be used as the end product of the process according to the invention to use.

Hydrocarbons, chlorinated hydrocarbons, z. B. methylene chloride, chloroform, carbon tetrachloride, chloroctanes, chloropropanes, straight-chain aliphatic or carbocyclic sulfones, which may also be substituted can, in particular tetramethylene sulfone, also halopyrimidines, such as fluorochloropyrimidines, 2.4. 6-trichloropyrimidine, 2.4. 6-trichloro-5-chloromethylpyrimidine and tetrachloropyrimidine or one of the reaction components can be used.

Preferred solvents used are tetrachloropyrimidine and tetramethylene sulfone, The reaction can be promoted by acidic catalysts. As catalysts metals or metal salts may be mentioned, such as boron, aluminum, zinc, iron, cobalt, Nickel, antimony, tin, copper and their salts. Friedel crafts are particularly suitable Catalysts.

Aluminum chloride, iron (III) chloride and zinc chloride are preferably used as catalysts. By definition, the initial components contain remainders R to R5 (in addition to those in the group chlorine substituents contained) at least two halogen substituents of the type indicated, Cl substituents being preferred. According to a particularly preferred embodiment, monochloroacetonitrile or acetonitrile is reacted with trichloromethyl isocyanide dichloride at the specified temperatures, preferably in the temperature range from about 1500 to 350 ° C., tetrachloropyrimidine or trichloropyrimidine being obtained in very good yields. The process according to the invention is therefore particularly suitable for the production of tetrachloropyrimidine from trichloromethyl isocyanide dichloride and monochloro racetonitrile, and for the production of 2,4,6-trichloropyrimidine from trichloromethyl isocyanide dichloride and acetonitrile.

The course of the reaction in the new process is surprising.

The products of the process are known intermediates, for example suitable for the production of reactive dyes.

Example 1 43 g of trichloromethyl isocyanide dichloride are added to a 0.3 liter enamel autoclave and 8.2 g of acetonitrile in 100 ml of carbon tetrachloride were heated to 250 ° C. for 5 hours. The reaction product is then filtered and the carbon tetrachloride is filtered off at normal pressure distilled off; then at 10 mm Mg between 890 and 93 0C the 2, 4, 6-trichloropyrimidine goes above. Yield: 30 R 82 Ho% of theory. M.p. 210C Example 2 43 g trichloromethyl isocyanide dichloride and 28.8 g trichloroacetonitrile are in one 0.3 liter VA autoclave heated to 300 ° C. for 4 hours. The oily tetrachloropyrimidine obtained is roughly distilled in a jet vacuum and the distillate is recrystallized from methanol. Yield 37.5 g of # 86% of theory. Mp. 67 ° C. Example 3 43 g of trichloromethyl isocyanide dichloride and 17.5 g of chloroacetonitrile are in a 0.3 liter enamel autoclave for 4 hours heated to 250 ° C. The oil obtained is then distilled in a water jet vacuum. Yield 31 g = 71% of theory tetrachloropyrimidine.

Example 4: 2,4,6-Trichloro-5- (p-nitrophenyl) -pyrimidine In a 0.3 1 enamel autoclave are 16.2 g of 4-nitrobenzyl cyanide, 21.5 g of trichloromethyl isocyanide dichloride, 0.5 g of iron (III) chloride in 100 ml of carbon tetrachloride heated to 2500 ° C. for 2 hours. After cooling, it is concentrated and the residue is recrystallized from white spirit rt.

M.p. 187-188 ° C C H N Cl calc .: 39.44 1.32 13.80 34.93 found: 39.72 1.59 13.45 34.65 over,: 304.54 MW found: 297 Example 5r 2,4,6-trichloro-5-methylpyrimidine In a 0.7 l nickel autoclave equipped with a stirrer and cooler, 129 g of trichloromethyl isocyanide dichloride, 33 g of propionitrile and 300 ml of carbon tetrachloride in the presence of catalytic amounts Iron (III) chloride heated to 200 ° C for one hour and 250 ° C for one hour. The pressure is kept at 25 atU by releasing the pressure through the cooler. After the reaction has ended is filtered, the solvent is concentrated and the residue is recrystallized from alcohol.

Yield: 51.5 g (61% of theory) m.p .: 68 ° C, lit. m.p .: 67-68 ° C example 6: 2,4,6-Trichloro-5-chloromethylpyrimidine. 43 g of trichloromethyl isocyanide dichloride and 17.8 g of 3-chloropropionitrile, dissolved in 100 ml of carbon tetrachloride. The reaction mixture is heated to 230 ° C. for 3 hours heated. After cooling, the residue is suctioned off and the filtrate Solvent distilled off.

The distillation residue is recrystallized from acetonitrile and thus obtained the 2,4,6-trichloro-5-chloromethylpyrimidine.

M.p .: 103-1050C C H N Cl calc .: 25.90 0.87 12.08 61.16 found: 26.10 1.01 11.95 61.0 MOber .: 231.92 MW found: 230 Example 7: 2,4,6-trichloro-5-phenylpyrimidine 11.7 g of benzyl cyanide and 21.5 g of trichloromethyl isocyanide dichloride are in 100 ml Carbon tetrachloride and dissolved in a shaking autoclave in the presence of 0.5 g of iron (III) chloride heated to 230 ° C. for 2 hours. After cooling and filtering is concentrated and the residue obtained is triturated with petroleum ether. The solid product is recrystallized from alcohol.

Yield: 16.4 g (63 ffi of theory). M.p .: 1590C C H N Cl calc .: 46.30 1.94 10.80 41.0 found: 46.60 2.19 10.8 40.72 over. : 259.54 MGf .: 265 example 8: 2.4.6.-Trichloropyrimidine 380 parts of tetramethylene sulfone are placed in a stirred tank and 5 gr. Fe3 chloride subl. filled. The mixture is heated to 220 ° and the solution is added dropwise of 654 parts of trichloromethyl isocyanide dichloride, 135 parts of acetonitrile and 9 parts Fe3-chloride subl. within 21/2 hours. There is a lively development of HCl a. The temperature falls to 1650. The heating is again reached after 2000. The reaction mixture is distilled through a column, 480 parts are obtained Kp15 90-105 °; nD20: 1, 5687. This fraction consists of 98.5% trichloropyrimidine, this corresponds to a yield of 85% of theory Example 9: tetrachloropyrimidine 150 parts of tetrachloropyrimidine and 2.5 parts of Fea chloride are heated to 2000. The solution of 218 parts of trichloromethyl isocyanide dichloride is added dropwise to this, 75.5 parts of monochloroacetonitrile and 4 parts of Fea chloride within 1 hour. 15 minutes is readjusted at 2000. Distillation of the reaction mixture gives 346 parts of tetrachloropyrimidine.

Kpl5 105-1120, melting point 64 °, yield: 90% of the theoretical example 10: 2.4.6-Trichlor-5- (3.4-dichlorophenyl) -pyrimidine 108 parts of trichloromethyl isocyanide dichloride, 98 parts of 3,4-dtchlorobenzyl cyanide, 500 parts of carbon tetrachloride and 0.5 Parts Fe3 chloride are heated to 2500 in a Ni autoclave for 1 hour. Relaxed at the same time the resulting HCl via a Ni cooler in a pressure interval of 30 - 50 atm. The reaction mixture after you have distilled off the solvent, 180 parts of the residue, the Recrystallized from ligroin gives 86 g of melting point 1410.

Analysis: nitrogen chlorine calc. 8.6% 54.0% found. 8.8% 54.0% 8.9 % 54.1% Example ii: 2.4.6-Trichloro-5- (2.3.4-trichlorophenyl) -pyrimidine As in the preceding For example, 105 parts of 2.3.4-trichlorobenzyl cyanide with 103 parts of trichloromethyl isocyanide dichloride are used reacted in carbon tetrachloride in the presence of Fe3 chloride. You get that Trichlorophenyl pyrimidine.

Mp. 198-2000 nitrogen chlorine over 7.7% 58.6 St0 found. 7.5% 57.9 % 7.7% Example 12: 2.4. 6-Trichloropyrimidine In a 500 ml four-necked flask using a dropping funnel, intensive condenser, stirrer and stopper, 200 g of 2,4,6-trichloropyrimidine are obtained and 5g ferric chloride heated to 205 ° C. A mixture is made every hour from 1 mol of trichloromethyl isocyanide dichloride (215 g) and 1 mol of acetonitrile (41 g) dropped into the four-necked flask. The temperature does not drop below 2O00C. is the 500 ml flask is filled and stirred for 15 minutes without dropping. where the Internal temperature rises to 21,000. Through the plugged neck of the flask half of the 2,4,6-trichloropyrimidine is sucked off hot and then the Continued dropping. If the conversion rate is too slow, iron (III) chloride must be used be followed up.

After adding 1935 g of trichloromethyl isocyanide dichloride and 369 g Acetonitrile (9 mol) the reaction was terminated.

A total of 45 g of ferric chloride were gradually added, what 5 g of iron (III) chloride / mole of trichloromethyl isocyanide dichloride. The used 200 g of 2,4,6-trichloropyrimidine are recovered.

Yield: 1375 g of 2,4,6-trichloropyrimine = 83% of theory boiling point 10 : 89-93 0C Example 13: 2.4. 6-Trichloropyrimidine In a 1.5 1 three-necked flask with dropping funnel, stirrer and intensive cooler are 300 g of tetrachloropyrimidine submitted and heated to 21,000 internal temperature after the addition of 5 g of iron (III) chloride.

A mixture of 43o g of trichloromethyl isocyanide dichloride is added within 3 hours (2 mol) and 82 g of acetonitrile (2 mol) were added dropwise. After adding 5 g of E4sen-11 chloride within a further three hours another 2 mol (430 g of trichloromethyl isocyanide dichloride, 82 g of acetonitrile) were added. The internal temperature does not fall below 20500. The mixture is stirred for 15 minutes and the resulting reaction mixture is distilled in vacuo.

951 g of distilled product are obtained, of which 900 g are used Tetrachloropyrimidine, 635 g of 2,4,6-trichloropyrimidine and 17 g of trichloromethyl isocyanide dichloride.

Yield: 635 g 2,4,6-trichloropyrimidine = 88% of theory Boiling point10: 89-93 ° C EXAMPLE 14: 2.4.6-Trichloro-5- (p-nitrophenyl) -pyrimidine 150g of tetrachloropyrimidine and 3g of iron chloride are placed in a three-necked flask Stirring heated to 1500C and a mixture of 107.5g trichloromethyl isocyanide dichloride and 81 g of p-nitrobenzyl cyanide were added and the mixture was heated to 210 ° C. for 2 hours. After that, will the reaction mixture is distilled. 150g of tetrachloropyrimidine are recovered.

Yield: 108 g = 72% of theory, melting point: 187-1880C (from petroleum ether) Analysis: C H N C1 calc .: 39.44 1.32 13.80 34.93 found: 39.51 1.35 13.62 34.98 MGber: 304.54 MGger 305 Example 15: 2.4.6-Trichloro-5-phenylpyrimidine In a three-necked flask 3g iron (III) chloride and 150g tetrachloropyrimidine are heated to 2100C and a Mixture of 107.5 g of trichloromethyl isocyanide dichloride and 58.5 g of benzyl cyanide within added dropwise from 1 hour. The temperature does not fall below 200 ° C. It's turning 30 Stirred at 205 ° C. for minutes.

The reaction mixture obtained is distilled, 150 g Tetrachloropyrimidine obtained, the crude reaction product distilled between Kpo, s: 130-160 ° C.

Yield: 71 g = 57% of theory (from Waschbensin). Melting point: 158 - 159 ° C Analysis: C H N C1 calc .: 46.30 1.94 10.80 41.0 found: 46.23 1.87 11.05 41.25 MWber: 259.54 MWgef: 261 Example 16: 2.4.6-Trichloro-5-chloromethylpyrimidine 300g trichloropyrimidine and 5g iron (III) chloride are placed in a three-necked flask and heated to 2100C. Now a mixture of 43Cg of trichloromethyl isocyanide dichloride is used and 178 g of 3-onloropropionitrile were added dropwise over the course of 4 hours. The internal temperature is kept between 205 and 2100C. After the end of the dropping, 30 minutes stirred and the contents of the flask are distilled in a water jet vacuum. The used 300 g of trichloropyrimidine are recovered.

Yield: 344 g = 74% of theory Melting point: 112 ° C. (from petroleum ether) Analysis: C H N C1 calc .: 25.90 0.87 12.08 61.16 found: 25.84 0.83 12.35 61.20 Example 17: 2.4.6-Trichloro-5-chloromethylpyrimidine 123g 2,4,6-trichloro-5-chloromethylpyrimidine and 5g iron (III) chloride are heated to 210 ° C. with stirring and a mixture from 215g trichloromethyl isocyanide dichloride and 89.5g 3-chloropropionitrile within one hour dripped. After stirring for 30 minutes, the petroleum ether becomes recrystallized. The 123g of 2,4,6-trichloro-5-chloromethylpyrinidine used are recovered.

Yield: 152 g = 65% of theory, melting point: 11200

Claims (10)

Claims: 1) Process for the preparation of halopyrimidines, characterized in that nitriles of the formula wherein R is hydrogen, fluorine, chlorine, bromine, ititro, alkyl, alkyl, cycloalkyl, aryl, nitrile, alkoxy, acyl, acyloxy or carbalkoxy substituents and R1 and R2 are independently hydrogen , Fluorine, chlorine or bromine substituents mean with isocyanide dichlorides of the formula where R is hydrogen, i? luor, chlorine, 3rom, alkyl, aralkyl, cycloalkyl, aryl or aromatic-heterocyclic radicals and R4 and R5 are independently hydrogen, fluorine, chlorine or bromine substituents , wherein at least two of the radicals R to R5 are fluorine, bromine or preferably chlorine substituents, and the alkyl, nralkyl, aryl and hetero radicals can have further substituents, optionally in the presence of catalysts to form halopyrimidines. 2) Method according to claim 1, characterized in that the Implementation in the presence of cyclic sulfones or ralogen pyrimidines as Solvent carries out. 3) Process according to claim 1 and 2, characterized in that one the reaction is carried out in the presence of metal or metal salt catalysts. 4) Process according to claim 1 and 2, characterized in that one the reaction is carried out in the presence of Friedel-Crafts catalysts. 5) Method according to claim 1-4, characterized in that one one of the output components is used in excess and this at the same time as a solution or diluents are used. 6) Method according to claim 1-5, characterized in that one Reacts chlorinated alkyl isocyanide dichlorides with acetonitrile. 7) Method according to claim 1-5, characterized in that one Reacts chlorinated alkyl isocyanide dichlorides with chlorinated acetonitriles. 8) Method according to claim 1-6, characterized in that one Trichloromethyl isocyanide dichloride with acetonitrile at temperatures of about 1000 converts to 2,4,6-trichloropyrimidine up to about 300 ° C. 9) Method according to claim 1-7, characterized in that one Trichloromethyl isocyanide dichloride and monochloroacetonitrile at temperatures of about 100 to about 3000C to tetrachloropyrimidine. 10) Halogen pyrimidines obtained by the process of claims 1-9.