DE1670854A1 - Process for the preparation of halopyrimidines - Google Patents

Description

FARBENFABRIKEN BAYER AG ^1670854

LEVERKUSEN-Bayemerk 23 FEB 1970 Pstent Abbey «/

Process for the preparation of halogen pyrimidines

Halopyrimidines are known from the literature. In the above-described process for their production, the Synthesis generally over several stages, the last stage being a chlorination of the heterocyclic ring will.

It has now been found that you can use halopyrimidines on new and can be prepared in a very simple manner in one process step if nitriles of the general formula

I ¹

H — O OH (I)

Bit isocyanide dichlorides of the general formula \

I ⁺

Cl
- C — ff ₌ c ^ (II)

I ^ *

^Β 5

converts} in the general formulas (I) and (II) are R Hydrogen, fluorine, chlorine, bromine, nitro, alkyl, aralkyl, Cycloalkyl, aryl, nitrile, alkoxy, acyloxy, carbalkoxy, acyl, such as arylsulfonyl or alkylsulfonyl substituents,

Le A 10 692 - 1 -

109812/174 7

IL. and R ₂ independently of one another is hydrogen, fluorine, chlorine or bromine substituents, IU hydrogen, fluorine, chlorine, bromine, alkyl, aralkyl, cycloalkyl, aryl or aromatic-heterocyclic radicals #R and Rc independently from each other hydrogen, fluorine, chlorine or bromine substituents, where at least two of the radicals R to R, - are fluorine, bromine or preferably chlorine substituents, and where the alkyl, aralkyl, aryl and hetero radicals have further substituents can, such as hemogen (e.g. CIf Br or F), cyano, nitro groups.

The starting components (I) and (II) are approximately stoichiometric proportions or · with an overfeed shot of one or the other component implemented together.

Nitriles of the formula (I) which are suitable for the process are, for example, acetonitrile, chloroacetonitrile, dichloroacetonitrile, irichloroacetonitrile, bromoacetonitrile, dibroraacetonitrile, tribromoacetonitrile, nitroacetonitrile, dichloro-nitro-acetonitrile, dibromo-nitro-acetonitrile, chloropropyl nitrile, propionyronitrile ß, Jr'-Mchlorbutyronitril, dL -Methyl-C ^ -chlorobutyronitril, Palmitonitril _f Äthoxydichloracetonitril, MaIodinitril, Methoxyacetonitril, Acetoxyacetonitril, ot-Methoxypropionitril, Acetyiacetonitrile, Phenylcyanlor-acetonitrile, Phenylcyanidenitryl-acetonitrile, phenyl-cyanitrile, Acetyiacetonitrile p-bromobenzyl cyanide ₉ o-nitrobenzyl cyanide, o (-naphthylacetonitrile, W ß-ip-toluyl-sulfonylJ-propionic acid nitrilejoC-sulfonylacetonitriles, such as methylsulfonyl- or ethylsulfonylacetonitrile.

Isocyanide dichlorides of the formula (II) suitable for the process are, for example, chloromethyl isocyanide dichloride, trichloromethyl isocyanide dichloride, Pentachloroethyl isocyanide dichloride, methyl isocyanide dichloride, dodecyl isocyanide dichloride, benzyl isocyanide dichloride, substituted benzyl isocyanide dichlorides, such as 3,4-dichlorobonzyl isocyanide dichloride and 1 ', 1'-dichlorobenzyl isocyanide dichloride.

Le A to 692 - 2 -

1038t2 / t747

The inventive method is carried out in the presence or absence of inert solvents vein diluent, conveniently at temperatures between 20 ° and 600 ⁰ C} the reaction at temperatures between 150 ° and 35O ⁰ C is preferably carried out, with atmospheric or superatmospheric pressure, and optionally in the gas phase can be worked. ' In general, it is advantageous to heat the starting components together in stoichiometric amounts, or to use one of the components as a solvent.

Hydrocarbons, chlorinated hydrocarbons, e.g. ethylene chloride, chloroform, carbon tetrachloride, Chlorethane, Chlorporpane or one of the reaction components can be used.

The reaction can be promoted by acidic or basic catalysts.

By definition, the starting components contain as residues

^ Cl

R to R _c (in addition to the ⁵ ^ Cl

Chlorine substituents) at least two halogen substituents of the type indicated, Cl substituents being preferred. According to a particularly preferred embodiment, trichloroacetonitrile or acetonitrile with trichloromethyl isocyanide dichloride at the indicated temperatures, preferably up to 35O ⁰ C in the temperature range of about 150 °, is obtained in very good yields tetrachloropyrimidine or trichloropyrimidine. The process according to the invention is therefore particularly suitable for the production of tetrachloropyrimidine from trichloromethyl isocyanide dichloride and trichloroacetonitrile, 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.

Le A 10 692 - 3 -

109812/1747

The products of the process are known intermediates which can be used, for example, for the preparation of reactive dyes. suitable.

Example 1 . _r

In a 0.3 liter enamel autoclave, 43 g of trichloromethyl isoeyanide dichloride and 8.2 g of acetonitrile in 100 ml of carbon tetrachloride are heated to 250 ° C. for 5 hours. The reaction product is then filtered and the carbon tetrachloride is distilled off at normal pressure; then the 2,4,6-trichloropyrimidine passes over at 10 mm Hg between 89 ° C. and 93 ° C. Yields 30 g ~ 82 i> of theory. P.p. 21 ° C

Example 2

43 g of trichloromethyl isocyanide dichloride and 28.8 g of trichloroacetonitrile are heated to 300 ° C. for 4 hours in a 0.3 liter VA autoclave. The oily tetrachloropyrimidine obtained is roughly distilled in a water jet vacuum and the distillate is recrystallized from methanol. Yield 37.5 ^ 'δδ fo of theory. Pp. 67 ⁰ C

Example 3

43 g of trichloromethyl isocyanide dichloride and 17.5 g of chloroacetonitrile are heated for 4 hours at 25O ⁰ C in a 0.3 liter autoclave enamel. The oil obtained is then distilled in a water jet vacuum. Yield 31 g = 71 $> the theory tetrachloropyriinidine, pp .: 67 ⁰ C.

Example 4

2,4,6-trichloro-5- (p-nitrophenyl) pyrimidine

In a 0.3 l enamel autoclave, 16.2 g of 4-nitrobenzyl

Le A 10 692 - 4 -

109812/1747

cyanide, 21.5 g of trichloromethyl isocyanide dichloride, 0 ^ 5 g of iron (III) chloride in 100 ml of carbon tetrachloride ^{heated to 250 °} C. for 2 hours. After cooling, the mixture is concentrated and the residue is recrystallized from white spirit. Mp .: 172 to 176 ⁰ C.

CH N Cl

ber .: 39 , 44 1 , 32 ^r 13. > 97 80 34, 93 found: 39 , 72 1 , 59 13, 45 34, 65 " ¹ W ^,! - 504 , 54 example 5

2,4,6-trichloro-5-nieth.ylpyrimidine

In a 0.7 1 nickel autoclave equipped with stirring and condenser, 129 g Triehlormethylisocyaniddichlorid, 33 g of propionitrile and 300 ml of carbon tetrachloride, iron-III chloride is heated in the presence of catalytic amounts of one hour at 200 C and one hour at 250 ⁰ C. . The pressure is kept at 25 atmospheres by releasing the pressure through the cooler. After the reaction has ended, it is filtered, the solvent is concentrated and the residue is recrystallized from alcohol.

Yield: 51 g (61 $> of theory) |

Mp, * 68 ⁰ C, lit. mp .: 67-68 ⁰ C

Example 6
2,4 »6-trichloro-5-chloromethylpyrimidine

43 g of trichloromethyllaoeyanide dichloride and 17.8 g of 3-chloropropionitrile, dissolved in 100 μl of carbon tetrachloride, are placed in a 0.3 l nickel autoclave. The Reaktionamischung is heated for 3 hours at 23O ⁰ C. After cooling down, the

Le A 10 692 - 5 -

109812/1747

Sucked off residue and distilled off the solvent from the filtrate. The distillation residue is recrystallized from acetonitrile and with it the 2,4,6-trichloro-5-chloromethylpyrimidine get-texu

Smp.j 103-105 ⁰ C.

C HN Cl

ber .: 25.90 0, 87 12th , 08 61 , 16 .f .: 26.10 1, 01 11 , 95 61 , 0 "W 231.92 ef. ¹ ι 230 example 7th

2,4, δ-trichloro-S-phenylpyrimidine

11.7 g of benzyl cyanide and 21.5 g Trichlormethylisocyaniddichlorid are dissolved in 100 ml of carbon tetrachloride and heated in a shaking autoclave in the presence of 0.5 g of egg-sen-III chloride for 2 hours at 23O ⁰ C. After cooling and filtering, the mixture is concentrated and the residue obtained is triturated with petroleum ether. The solid product is recrystallized from alcohol.
Yield »16.4 g ( $ 63 of theory). M.p .: 159 ° C

C H N Cl

ber * ι 46, 30th ^{M (J found} . 1 , 94 10 , 80 41, 0 found " 46, 60 2 , 19th 10 ,8th 40, 72 ^MS b _e r. ' 259.54 t 265 example 8th

2,4,6-trichloropyrimidine

Le A 10 692 - 6 -

109812/1747

In a stirred tank, 380 parts of tetramethylene sulfone Tind 5 g of Fe ^ chloride subl. filled. The mixture is heated to 220 ° and the solution of 654 parts of trichloromethyl isocyanide dietiloride, 135 parts of acetonitrile and 9 parts of Fe ^ chloride subl. a within 2 ^1/2 hours. . Here is lively HCl evolution an "The temperature drops to 165 ° C is heated to 200 ⁰ C again be achieved The reaction mixture is distilled through a column, thereby to obtain 480 parts of Kp ₁₅ 90 -.. 105 ⁰ J n ^ _Q: 1, 5687th This fraction consists of 98.5 ° from i trichloropyrimidine, which corresponds to a yield of 85 i> of theory..

Example 9
Tetrachloropyrimidine

150 parts of tetrachloropyrimidine and 2.5 parts of Fe, chloride are heated to 200 ⁰ C. For this purpose, is added dropwise the solution of 518 parts of trichloromethyl isocyanide, "75.5 parts Monochloracetonitril and 4 parts of Fe, -ehlorid within 1 hour a. 15 minutes' stirring at 200 ⁰ C. Distillation of the reaction mixture gives 346 parts of tetrachloropyrimidine. Bp ₁₅ 105-112 °, melting point 64 °, yield: 90 # of theory.

Example 10 '
2.4.6-Trichloro-5- (3.4-dichlorophenyl) pyrimidine

108 parts Trichlormethylisooyaniddichlorid, 98 parts of 3,4-di- 'chlorobenzyl cyanide, 500 parts of carbon tetrachloride and 0.5 parts of Fe-z ehlorid are heated for 1 hour at 25O ⁰ C in a Ni autoclave. The resulting HCl is released via a Ni cooler in a pressure interval of 30 - 50 atmospheres. After the solvent has been distilled off, the reaction mixture gives 180 parts of the residue, which recrystallizes from ligroin

Le A 10 692 - 7 -

109812/1747

86 g rom mp. 141 ⁰ C results.

Analysis t nitrogen 1 chlorine ber. $ 8.6>
- ψ- 54.0 gef · 8.8 f » 54.0 $ 8.9> 54.1 example 1

2.4.6-Triehloi * -5-X 2.5.4-trichiorphenyl} -pyrimid in

As in the previous example, 105 parts of 2 »3,4-trichlorobenzyl cyanide are used with 103 parts of trichloromethyl isocyanide dichloride in carbon tetrachloride in the presence of. Fe ~ - Chloride implemented. The tri chlorophenylpyimide is obtained in '.

"Chlorine. 58.6 i $ 57.9

M.p. 198 - 200 ° nitrogen $ 7.7> • ber. 7.5 f> found $ 7.7> example 12th

2.4.6-trichloropyrimidine

200 g of 2,4,6-trichloropyrimidine and 5 g of iron (III) chloride are heated ^{to 205 °} C. in a 500 ml four-necked flask with a dropping funnel, intensive condenser, stirrer and stopper. A mixture of 1 mol of trichloromethyl isocyanide dichloride (215 g) and 1 tlol of acetonitrile (41 g) is added dropwise to the four-half flask every hour. The temperature does not fall below 200 thereby ⁰ C. If the 500 ml flask filled, then stirred for 15 minutes without the dropwise addition, the internal temperature rises to 21O ⁰ C. Half of the 2,4,6-trichloropyrimidine is drawn off hot through the stoppered neck of the flask.

Le A 10 692 - 8 -

109812/1747

sucks and then continued the dropping. .Will the If the reaction rate is too slow, iron (III) chloride must be added. After adding 1935 g of trichloromethyl isocyanide dichloride and 369 g of acetonitrile (9 mol) the reaction was terminated.

A total of 45 g of ferric chloride were gradually added, which is 5 g of iron (III) chloride / mole of trichloromethyl isocyanide dichloride is equivalent to. The 200 g of 2.4.6-trichloropyrimidine used are recovered. ■.

Yield: 1375 g of 2.4.6-trichloropyrimidine = 83 $ of the theory boiling point., _Q : 89 - 93 ⁰ C ...

Example 13 ■ g

2, A .6-Trichloropyrimidine

Funnel, a stirrer in a 1.5 1 three-necked flask with drip and intensive cooler 300 g tetrachloropyrimidine are introduced and after addition of 5 g of ferric chloride was heated to 21Q ⁰ C internal temperature.

A mixture of 430 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 iron (III) chloride are within another three hours another 2 moles (430 g of trichloromethyl isocyanide dichloride, 82 g of acetonitrile) were added. The internal temperature does not fall below 2O5 ° C. It will be 15 f Stirred minutes and the reaction mixture obtained is distilled in vacuo.

951 g of distilled product are obtained, 300 g of which are tetrachloropyrimidine used, 635 g of 2,416-trichloropyrimidine and 17 g of trichloromethyl isocyanide dichloride. Yields 635 g of 2,4,6-trichloropyrimidine = 88 $> the theory boiling point ₀ * 89-93 ⁰ C.

Le A 10 692 - 9 -

109812/1747

Example 14 '' / 0

2.4.6-Trichloro-5- (p-nitrophenyl) pyrimidine

In a three-necked flask, 150 g of tetrachloropyrimidine and 3 g of iron (III) chloride are ^{heated to 150 °} C. with stirring and a mixture of 107.5 g of trichloromethyl isocyanide dichloride and 81 g of p-nitrobenzyl cyanide are added and the mixture is heated to 210 ^° C. for 2 hours. The reaction mixture is then distilled. 1.50 g of tetrachloropyrimidine are recovered. > Yield: 108 g = 72 # of theory m.p .: 187 - 188 ⁰ C (from petroleum ether)

Analysis: ber. s C. , 44 H 32 N , 80 Cl , 93 found: 39 , 51 1, 35 13th , 62 34 , 98 »<W 304.54 39 ^{MG found} 1, 305 13th 34 Example 15 :
•

2.4.6-Trichloro-5-phenylpyrimidine

In a three-necked flask, 3 g of ferric chloride are heated and .150 g tetrachloropyrimidine to 21O ⁰ C and added dropwise a mixture of 107.5 g and 58.5 g of benzyl cyanide Trichlormethylisocyaniddichlorid within "1 hour. The temperature does not fall below 200 thereby ⁰ C. It is 30 minutes at 205 ⁰ C stirred the reaction mixture obtained is distilled, during which 150 g tetrachloropyrimidine be obtained, the crude reaction product was distilled between _Κρ Λ.,: 130 - 16O ⁰ C. yield: 71 g = 57 i "of Theory (from petroleum ether) melting point t 158 - 159 ⁰ C

Le A 10 692 - 10 -

109812/1747

ft 167Ö854

Analyzes ⁴ CHN Eq

ber.:. 46.30, 1.94 10.80 41.0

found i 46.23 1.87 11.05 41.25

. 259.54 MG _Found; 261

Example 16
2.4.6-Trichloro-5-chloromethylpyrimidine

300 g Trichlorpyrimiäin and 5 g of ferric chloride are introduced into a three-necked flask and heated to 210 ⁰ C. A mixture of 430 g of trichloromethyl isocyanide dichloride and 178 g of 3-chloropropionitrile is now added dropwise over the course of 4 hours. The internal temperature is kept between 205 and 210 ° C. After the dropping has ended, stirring is continued for 30 minutes and the contents of the flask are distilled in a water jet vacuum. The 300 g of trichloropyrimidine used are recovered.

Yield * 344 g = 74 1 ° of theory Melting point: 112 ⁰ O (from petroleum ether)

Analysis: ber · j C. - H N 08 Cl gef.i 25, 90 0.87 12, 35 61.16 Example 17 25, 84 0.83 12, 61.20

2.4. Ö -trichloro-S-chloromethylpyrimidine

123 g of 2,4,6-trichloro-5-chloromethylpyrimidine and 5 g of iron (III) chloride are ^{heated to 210 °} C. with stirring and a mixture of 215 g of trichloromethylisoyanide dichloride and 89.5 g of 3-chloropropionitrile are added dropwise over the course of one hour. After stirring for 30 minutes, the petroleum ether is crystallized

Le A 10 692 - 11 -

109812/1747

1670864

lized. The 123 g of 2,4,6-trichloro-5-chloromethylpyrimidine used are recovered. Yield: 152 g = 65 ° i of theory Melting point: 112 ⁰ C.

Le A 10 692 - 12 -

1098 1 2/1747

Claims (8)

Claims R C CN H ₂ - wherein R is hydrogen, fluorine, chlorine, bromine, nitro, alkyl, aralkyl, cycloalkyl, aryl, nitrile, alkoxy, Acyl, acyloxy or carbalkoxy substituents and R. and Rp independently of one another are hydrogen, Mean fluorine, chlorine or bromine substituents, with isocyanide dichlorides of the formula -N = O ^X c— Ns ι ^ Cl ^ Cl wherein R, hydrogen, fluorine, chlorine, bromine, alkyl, aralkyl, cycloalkyl, aryl or aromatic heterocyclic Radicals and R. and R, - independently of one another Hydrogen,. Fluorine, chlorine or bromine substituents mean, where at least two of the radicals R to Rc are fluorine, bromine or preferably chlorine substituents, and where the alkyl, aralkyl, aryl and hetero radicals can have further 3ub3tituenten, converts with the formation of halopyrimidines. Le A 10 692 - 13 - 109812/1747 2) Process according to claim 1, characterized in that the unisetzung in the presence or absence of inert solvents or diluents at temperatures of 20 ⁹ C, preferably at temperatures of 150-35O ⁰ C, is carried out. 3) Method according to claim 1, characterized in that one of the starting components is used in excess and this is also used as a solvent or diluent • * 4) Process according to claim 1, characterized in that chlorinated alkyl isocyanide dichlorides with acetonitrile implements. 5) Process according to claim 1, characterized in that chlorinated alkyl isocyanide dichlorides with chlorinated ones Acetonitrile converts. 6) Method according to claim 1, characterized in that trichloromethyl isocyanide dichloride and trichloroacetonitrile at temperatures chloropyrimidine converts. nitrile at temperatures of approx. 150 - approx. 35O ⁰ C to tetra- 7) A method according to claim 1, characterized in that acetonitrile with trichloromethyl isocyanide dichloride at temperatures of about 150 ° - reacting about 35O ⁰ C to 2,4,6-trichloropyrimidine. 8) Halopyrimidines obtained by the process of claims 1-7. Le A 10 692 - 14 - 109812/1747