CA1117943A - 2,4,6-trihalopyrimidine-5-carboxylic acid halides and process for their preparation - Google Patents
2,4,6-trihalopyrimidine-5-carboxylic acid halides and process for their preparationInfo
- Publication number
- CA1117943A CA1117943A CA000356537A CA356537A CA1117943A CA 1117943 A CA1117943 A CA 1117943A CA 000356537 A CA000356537 A CA 000356537A CA 356537 A CA356537 A CA 356537A CA 1117943 A CA1117943 A CA 1117943A
- Authority
- CA
- Canada
- Prior art keywords
- trihalopyrimidine
- carboxylic acid
- formula
- aldehyde
- chlorine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- 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
- C07D239/28—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
Abstract
2,4,6-TRIHALOPYRIMIDINE-5-CARBOXYLIC ACID HALIDES AND
PROCESS FOR THEIR PREPARATION
Abstract of the disclosure:
2,4,6-Trihalopyrimidine-5-carboxylic acid halides are prepared by reaction of 2,4,6-trihalopyrimidine-5-aldehydes with chlorine and/or at least one chlorinating agent (sulfuryl chloride etc.), optionally in the presence of a free radical-forming agent, at temperatures of from about 20 to 150°C, in an inert organic solvent, and op-tionally rehalogenation of the 2,4,6-trihalopyrimidine-5-carboxylic acid chlorides formed with usual fluorinating or brominating agents. The products are intermediates especially in the field of dyestuffs.
PROCESS FOR THEIR PREPARATION
Abstract of the disclosure:
2,4,6-Trihalopyrimidine-5-carboxylic acid halides are prepared by reaction of 2,4,6-trihalopyrimidine-5-aldehydes with chlorine and/or at least one chlorinating agent (sulfuryl chloride etc.), optionally in the presence of a free radical-forming agent, at temperatures of from about 20 to 150°C, in an inert organic solvent, and op-tionally rehalogenation of the 2,4,6-trihalopyrimidine-5-carboxylic acid chlorides formed with usual fluorinating or brominating agents. The products are intermediates especially in the field of dyestuffs.
Description
~7~L3
- 2 - HOE 79/F 201 Pyrimidine derivatives are interesting intermediates and final products for diverse fields, for example for dyestuffs, plant protecting and pharmaceu2ical agents.
For example~2,4,6-trichloropyrimidine-5-carboxylic acid chloride is an interesting pyrimidine derivative.
This compound is listed in the two German Offenlegungs-schriften Nos. 2,113,298 and 2,208,972 among numerous reactive components for the manufacture of reactive dyes;
however, nothing in indicated there with respect to its preparation. Other corresponding p~ublications, for example German Offenlegungsschriften Nos. 1,670,854 and 1,770,774 referring to a process for the preparation of halopyri-midines from nitriles and isocyanide dichlorides, Iikewise do not indicate how 2,4,6-trichloropyrimidine-5-carboxylic acid chloride or, generally, 2,4,6-trihalopyrimidine-5-carboxylic acid halides are obtained.
It is therefore the object of the invention to pro-vide a simple and economic process for the preparation of 2,4,6-trichloropyrimidine-5-carboxylic acid chloride and other 2,4,6-trihalopyrimidine-5-carboxylic acid halides, and thus to make available these compounds for the industrial practice.
In accordance with the invention, this object has been achieved.
2S Subject of the invention are therefore 2,4,6-tri-halopyrimidine-5-carboxylic acid halides of the formula I
y1 ,~ COX
y~N ~ ~, in which X, y1~ y2 and Y3, independently from one another, are F, Cl, Br.
Compounds corresponding to this formula are for e~-ample ~ .
' , . . . . . .. . . . .
. . ,.. - . : : ,, :::: :
- . . ,. .; :, .
: .:, ,:, :, , , ., :,~ " . :
: .
~ 3 - HOE 79~F 201 F F
~ COF ,~ COC
Cl ~l~ Cl , Cl N Cl ~ Cl N ~ C~Br ~COCl Cl ~ N Cl , Cl ~ N Br , etc.
Preferred 2,4,6-trihalopyrimidine-5-carboxylic acid halides are those compounds of the formula I in which X y1 = y2 = y3~ that is:
~ Cl Br N~ COF ~ COC l N s~ COBr F ~ N ~ F Cl ~ Cl Br ~ N ~ Br Especially preferred is the compound of the formula I, 20 in which X = y1 = y2 = y3 = Cl, that is, 2,4,6-trichloro-pyrimidine-5-carboxylic acid chloride.
Subject of the invention is furthermore a process for the preparation of compounds of the formula I, which com-prises reacting 2,4,6-trihalopyrimidine-5-aldehydes of 5 the formula II
yl ~CI~O
, 30 in which y1 through Y3 are as defined in formula I, with chlorine and/or a chlorinating agent, optionally in the presence of a free radical-forming agent, at temperatures of from about 20 to 150C, preferably about 50 to 100C, in an inert organic solvent, and optionally rehalogenating 35 thereafter the 2,4,6-trihalopyrimi.dine-5-carhoxylic acid chloride formed with usual fluorinating or brominating agen~s.
, ~ ` , ; ' ' ' ' ' '' '''...., ' : , ~ ' .' ' ,` ' '' . `' ' ` ~' ' ' , :
.
Although it is known to convert benzaldehyde and some specially substituted ben~aldehydes, such as o-chloro-benzaldehyde, to the correspondiny acid chlorides by means of chlorine or chlorinating agents such as sulfuryl chloride alkyl hypochlorites, N-chlorosuccinimide etc. /see e.g.
H.T. Clarke and E.R. Taylor, Org. Synth. Coll. Vol. I, 155 ~1947); H.C. Brown, Ind. Eng. Chem. 36, 788 (1944), S. Goldschmidt, R. Endres and R. Dirsch, Ber. 58, 576 (1~25); Ginsburg, J. Amer. Chem. Soc. 73, 702 (1951); etc 7 this reaction does generally not occur at all, or it yields only benzaldehyde derivatives chlorinated in the nucleus.
Moreover, when alkyl hypochlorites are used as chlorinating agent, the corresponding carboxylic acid chlorides cannot be isolated but in some cases only. Be~ause of reaction of the acid chlorides with the intermediately formed alco-hols, this kind of conversion genera]ly aives esters or carboxylic acids directly.
For preparing heterocyclic carboxylic acid chlorides from the corresponding aldehydes, this kind of reaction has not been applied hitherto.
The reaction with chlorine and usual chlorinating agents proceeds according to the following scheme (the aromatic or heterocyclic radical of the starting alde-hyde being omitted):
-CHO t Cl2 - ~ -COCl + ~IC]
-C~IO + S~C12 ~ COCl ~ }IC~SO2 -CI~O + ~ C~ -COCl ~ ~
As starting compounds of the formula II for the pro-cess of the nvention there may be cited for example:
2,4,6-lr~hl~ro~yrimidine-5-aldehyde, 2,4,6-tribromo pyrimidine-5-aldehyde, 2,4,6-trifluoro-pyrimidine 5-aldehyde, 4-chloro-2,6-difluoro-pyrimidine-5-aldehyde, ' :' . .. .
- ; ., ,' : ' . : ':
, ., :
~IL79~3 - 5 - ~IOE 79/F 201 4~chloro 2,6-dibromo-pyrimidine-5-aldehyde, 2-chloro-4,6-difluoro-pyrimidine-5-aldehyde, 2-chloro-4,6-dibromo-pyrimidine-5-aldehyde, 2,4-dichloro-6-fluoro-pyrimidine-5-aldehyde, 4,6-dichloro-2-fluoro-pyrimidine-5-aldehyde, 2,4-dichloro-6 bromo-pyrimidine-5-aldehyde, 2,4-dichloro-2-bromo-pyrimidine-5-aldehyde etc.
Preferred starting compounds are 2,~,6-trifluoro-, 2,4,6-trichloro-, or 2,4,6-tribromo-pyrimidine-5-aldehyde;
especially preferred is 2,4,6-trichloro-pyrimidine-5-aldehyde.
The starting compounds are prepared as follows:
According to German Offenlegungsschrift No. 2,310,334, 2,4,6-trichloropyrimidine-5-aldehyde is obtained from bar-bituric acid, phosphorus oxychloride and dimethyl formamide.
Other 2l4~6-trihalopyrimidine-5-aldehydes can be obtained from this pyrimidine aldehyde by rehalogenation according to known methods, for example with AgF /Wempen and Fox, J. Med. Chem. 6, 588 (1963); Horwitz and Thomson, J.Ory.
Chem. 26, 3392 (1961)7, KF (Horwitz and Thomson, loc. cit.) K-fluorosulfinate (German Offenlegungsschriften Nos.
2,819,787 and 2,819,837), or PBr3/Caton, Hurst, McOmie and Hunt, J. Chem. Soc. (C) 1967. 12047etc.
The starting aldehydes of the formula II are con-verted to the corresponding acid chlorides by means of ~5 chlorine and/or a chlorinating agent; sulfuryl chloride or N-chlorosuccinimide being preferred. Chlorine or one of the cited chlorinating agents may be used per se, or 2 or more of the latter ones may be employed as mixture.
It is advantageous for the course of the reaction to use the reac~ants in a substantially stoichiometric ratio; however, the chlorinating agent may be present in excess.
As free radical forming agents there are used the compounds known for initiating radical reactions, such as organic~peroxides.~benzoyl peroxide etc.), or organic azo compounds (azo-bis-isobutyronitrile~. The free radical-forming agent is advantageously employed in catalytic : ~: .. , :, :
. . . . . : ~
..
, - 6 - ~OE 7g/F 201 amounts of from about 0.1 to 10 wei.ght ~, relative to the starting aldehyde II.
The reaction temperaturesare advantageously in the range of from about 20 to 150C, preferably from about 50 to 100C.
Suitable inert organic solvents are practically all those organic solvents in which at least the starting compound is soluble, and which react in no way neither with the starting compounds nor with the final products nor with the chlorinating agents and the free radical-forming agents. Preferred are chlorinated aliphatic hydrocarbons having from 1 to 4 carbon atoms, for example chloroform, carbon tetrachloride, hexachloroethane etc..
The ratio of solvents to the sum of the reactants may vary within relatively wide limits; generally, a weight ratio of from about 15:1 to about 3:1 of solvent to sum of starting aldehyde II and chlorinating agent is preferred.
Depending on the reaction temperature, the reaction time is from about 3 to 15, preferably about 3 to 10, hours.
In the reaction of 2,4,6-trihalopyrimidine-5-alde~
hydes with chlorine and/or one of the above chlorinating agent in accordance with the invention, first the corre-sponding acid chlorides only are formed, which can be rehalogenated, i~ desired, according to ~nown methods with usual fluorinating agents (anhydrous hydrofluoric acid, alkali metal fluorides, preferably NaF, KF or CsF, amrnonium fluorides, SbF3, SF4, K-fluorosulfinate etc.) 30 or brominating agents (PBr3 etc.) to give the corre- -sponding acid fluorides or bromides. In the case where the substituents y1~ y2 and/or Y3 are not the intended halogen, this rehalogenation may be continued until these substituents, too, are replaced by the intended ~ alo~.~n.~
In certai.n cases, for example when usinq PBr3, the rehalogenati.ng agent may serve as solvent for the re-halogenation.
:.: .;
, ~794~
,, ~
The reaction temperature for the rehalogenation sho~;ld be generally chosen in the range of from 20 to 250C, preferably 50 to 130C.
The 2,~,6-trihalopyrimidine-5-carboxylic acid hali-des of the above formula I in accordance with the inventionare interesting intermediates especially in the dyestuff field. For example, fiber-reactive dyestuffs are ob-tained by reacting the compounds of the formula I with amino group-containing dyestuffs according to the scheme indicated in German Offenlegungsschriften Nos. 2,113,298 and 2,208,972.
The following Examples illustrate the invention.
E X A M P L E
105.85 g (0.5 mol) of 2,4,6-trichloropyrimidine-5-aldehyde are dissolved in 500 ml anhydrous carbon tetra~chloride and, a~ter addition of 100 mg of azo-bis-iso-butyronitrile, heated to 60C with agitation. Subsequently r 67.48 g (0.5 mol) of sulfuryl chloride are slowly added dropwise. Thus, the solution is heated to boiling tempe-~0 rature, and viuorous de~elopment of hydrogen chlorideand sulfur dioxide starts. After a 4 hours' refluxing, furthe- 100 mg of azo-bis-isobutyronitrile and 6.75 g (0.05 mol~ of sulfuryl chloride are added, and refluxing is continued for another 4 hours. The light yellow solu-tion obtained is concentrated under reduced pressure, andthe yellow, partially crystalline residue is subjected to fractional distillation under reduced pressure.
Yield: 111.98 g of 2,4,6-trichloropyrimidine-5-carboxylic acid chlorida (91 w~%
of th.) b.p.: 73 - 76 at 1.63 mbar m.p.: 44 - 45C
E X A ~ P L E 2 105.85 g (0.5 mol) of 2,~,6-trichloropyrimidine-5 aldehy~e ~ 87.73 g (0.65 mol) of sulfuryl chloride in 500 ml of carbon tetrachloride are reacted as des-cribed in Example 1; however, the reaction time is pro-`' longed to 12 hours.
, I
, ~'7C3~
, - 8 - HOE 79/E~ 201 Yield: 117.52 g of 2,4,6-trichioro-pyrimidine-5-carboxylic acid chloride (96 Wt.~oL
th.) ' colorless crystals m.p.: 44 - 46C
21.15 g (0.1 mol) of 2,4,6-trichloropyrimidine-5-aldehyde are suspended in 100 ml of anhydrous carbon tetra-chloride. After having passed nitrogen through the sus-pension for 10 minutes, the batch is heated to 70C withagitation, 100 mg of benzoylperoxide are added, and 13.5 g (0.1 mol) of sulfuryl chloride are immediately added drop-wise, thus causing the reaction mixture to foam heavily.
After a 3 hours' agitation at reflux temperature (78C), the batch is allowed to cool, decanted from small amounts of precipitated solids, and the solvent is removed under reduced pressure. 16.72 g of a light yellow, semicrystalline mass is obtained. Distillation under reduced pressure gives 13.01 g of 2,4,6-trichloro-pyrimidine-5-carboxylic acid chloride, colorless crystals ~53 wt. %) b~p.: 73 - 76C at 1.6 mbar m~ 43 - 45C
4.92 g (20 mmols) of the 2,4,6-trichloropyrimidine-5-carboxylic acid chloride obtained according to Example 1 are agitated for 5 days at 110 - 120C with 75 ml of phos-phorus tribromide. The excess phosphorus tribromide is removed under reduced pressure, and the residue is sub-limated at 120 - 130C/0.15 mm.
Yield: 6.41 g of 2,4,6-tribromo-pyrimidine-5-carboxylic acid bromide m~.: 127 - 128C.
-2,4,6-trichlor~pyrlmidine-5-carboxyl~ acid bromide 21.15 g (0.1~moI')'`of '2,4,6-trichloro-pyrimidine-5-aldehyde, 19.58 g (0.1 mol) of N-bromosuccinimide and 100 mg of 2,2'-azo-bis-(2-methylpropionitrile) as chain .` " ~,, .`,. ,, ., ,,~!. -, . . .
initiator a~e suspended in 200 ml of ~nhydrous carbon tetrachloride, and heated for 3 hours to boiling tempe~
rature with agitation. After cooling, the solid succinimide is filtered off and the solvent is removed under reduced pressure. 34.1 g of crude acid bromide are obtained which are purified by distillation under reduced pressure.
Yield: 23.5 g (81 ~ of th.) of 2,4,6-trichloropyrimidine-5-carboxylic acid bromide mp.: 54 - 55C -b,p.: 84 - 90C at 0.35 - 0.4 mm IR: V = 1795 cm 1 -- c=o E X A M P I, E
.. . .
4,6-dichloro-pyrimidine-5-carboxylic acid chloride 14.85 g (0.11 mol) of sulfuryl chloride and 100 mg of 2,2'-azo-bis-(2-methylpropionitrile) as chain initiating agent are added to a suspension of 17.7 g (0.1 mol) of 4,6-dichloropyrimidine-5-aldehyde. Subsequently, the batch is heated to boiling temperature with agitation. After 3.5 hours, the vigorous development of hydrogen chloride and sulfur dioxide has come to an end. The clear, light yellow solution is liberated from the solvent under reduced pressure;22.5 g of crude acid chloride are obtained which are purified by distillation under reduced pressure.
Yield: 19.05 g (90.1 ~ of th.) of 4,6-dichloro-p~,rimi dine-5-carboxylic acid chloride b~p.: 60 - 62C at o.4 mm NMR (CDCl3): 8.9 ppm (1H, singulet) IR: VC=O = 1800 cm MS: molecular ~n m/e = 210 (3 Cl)
For example~2,4,6-trichloropyrimidine-5-carboxylic acid chloride is an interesting pyrimidine derivative.
This compound is listed in the two German Offenlegungs-schriften Nos. 2,113,298 and 2,208,972 among numerous reactive components for the manufacture of reactive dyes;
however, nothing in indicated there with respect to its preparation. Other corresponding p~ublications, for example German Offenlegungsschriften Nos. 1,670,854 and 1,770,774 referring to a process for the preparation of halopyri-midines from nitriles and isocyanide dichlorides, Iikewise do not indicate how 2,4,6-trichloropyrimidine-5-carboxylic acid chloride or, generally, 2,4,6-trihalopyrimidine-5-carboxylic acid halides are obtained.
It is therefore the object of the invention to pro-vide a simple and economic process for the preparation of 2,4,6-trichloropyrimidine-5-carboxylic acid chloride and other 2,4,6-trihalopyrimidine-5-carboxylic acid halides, and thus to make available these compounds for the industrial practice.
In accordance with the invention, this object has been achieved.
2S Subject of the invention are therefore 2,4,6-tri-halopyrimidine-5-carboxylic acid halides of the formula I
y1 ,~ COX
y~N ~ ~, in which X, y1~ y2 and Y3, independently from one another, are F, Cl, Br.
Compounds corresponding to this formula are for e~-ample ~ .
' , . . . . . .. . . . .
. . ,.. - . : : ,, :::: :
- . . ,. .; :, .
: .:, ,:, :, , , ., :,~ " . :
: .
~ 3 - HOE 79~F 201 F F
~ COF ,~ COC
Cl ~l~ Cl , Cl N Cl ~ Cl N ~ C~Br ~COCl Cl ~ N Cl , Cl ~ N Br , etc.
Preferred 2,4,6-trihalopyrimidine-5-carboxylic acid halides are those compounds of the formula I in which X y1 = y2 = y3~ that is:
~ Cl Br N~ COF ~ COC l N s~ COBr F ~ N ~ F Cl ~ Cl Br ~ N ~ Br Especially preferred is the compound of the formula I, 20 in which X = y1 = y2 = y3 = Cl, that is, 2,4,6-trichloro-pyrimidine-5-carboxylic acid chloride.
Subject of the invention is furthermore a process for the preparation of compounds of the formula I, which com-prises reacting 2,4,6-trihalopyrimidine-5-aldehydes of 5 the formula II
yl ~CI~O
, 30 in which y1 through Y3 are as defined in formula I, with chlorine and/or a chlorinating agent, optionally in the presence of a free radical-forming agent, at temperatures of from about 20 to 150C, preferably about 50 to 100C, in an inert organic solvent, and optionally rehalogenating 35 thereafter the 2,4,6-trihalopyrimi.dine-5-carhoxylic acid chloride formed with usual fluorinating or brominating agen~s.
, ~ ` , ; ' ' ' ' ' '' '''...., ' : , ~ ' .' ' ,` ' '' . `' ' ` ~' ' ' , :
.
Although it is known to convert benzaldehyde and some specially substituted ben~aldehydes, such as o-chloro-benzaldehyde, to the correspondiny acid chlorides by means of chlorine or chlorinating agents such as sulfuryl chloride alkyl hypochlorites, N-chlorosuccinimide etc. /see e.g.
H.T. Clarke and E.R. Taylor, Org. Synth. Coll. Vol. I, 155 ~1947); H.C. Brown, Ind. Eng. Chem. 36, 788 (1944), S. Goldschmidt, R. Endres and R. Dirsch, Ber. 58, 576 (1~25); Ginsburg, J. Amer. Chem. Soc. 73, 702 (1951); etc 7 this reaction does generally not occur at all, or it yields only benzaldehyde derivatives chlorinated in the nucleus.
Moreover, when alkyl hypochlorites are used as chlorinating agent, the corresponding carboxylic acid chlorides cannot be isolated but in some cases only. Be~ause of reaction of the acid chlorides with the intermediately formed alco-hols, this kind of conversion genera]ly aives esters or carboxylic acids directly.
For preparing heterocyclic carboxylic acid chlorides from the corresponding aldehydes, this kind of reaction has not been applied hitherto.
The reaction with chlorine and usual chlorinating agents proceeds according to the following scheme (the aromatic or heterocyclic radical of the starting alde-hyde being omitted):
-CHO t Cl2 - ~ -COCl + ~IC]
-C~IO + S~C12 ~ COCl ~ }IC~SO2 -CI~O + ~ C~ -COCl ~ ~
As starting compounds of the formula II for the pro-cess of the nvention there may be cited for example:
2,4,6-lr~hl~ro~yrimidine-5-aldehyde, 2,4,6-tribromo pyrimidine-5-aldehyde, 2,4,6-trifluoro-pyrimidine 5-aldehyde, 4-chloro-2,6-difluoro-pyrimidine-5-aldehyde, ' :' . .. .
- ; ., ,' : ' . : ':
, ., :
~IL79~3 - 5 - ~IOE 79/F 201 4~chloro 2,6-dibromo-pyrimidine-5-aldehyde, 2-chloro-4,6-difluoro-pyrimidine-5-aldehyde, 2-chloro-4,6-dibromo-pyrimidine-5-aldehyde, 2,4-dichloro-6-fluoro-pyrimidine-5-aldehyde, 4,6-dichloro-2-fluoro-pyrimidine-5-aldehyde, 2,4-dichloro-6 bromo-pyrimidine-5-aldehyde, 2,4-dichloro-2-bromo-pyrimidine-5-aldehyde etc.
Preferred starting compounds are 2,~,6-trifluoro-, 2,4,6-trichloro-, or 2,4,6-tribromo-pyrimidine-5-aldehyde;
especially preferred is 2,4,6-trichloro-pyrimidine-5-aldehyde.
The starting compounds are prepared as follows:
According to German Offenlegungsschrift No. 2,310,334, 2,4,6-trichloropyrimidine-5-aldehyde is obtained from bar-bituric acid, phosphorus oxychloride and dimethyl formamide.
Other 2l4~6-trihalopyrimidine-5-aldehydes can be obtained from this pyrimidine aldehyde by rehalogenation according to known methods, for example with AgF /Wempen and Fox, J. Med. Chem. 6, 588 (1963); Horwitz and Thomson, J.Ory.
Chem. 26, 3392 (1961)7, KF (Horwitz and Thomson, loc. cit.) K-fluorosulfinate (German Offenlegungsschriften Nos.
2,819,787 and 2,819,837), or PBr3/Caton, Hurst, McOmie and Hunt, J. Chem. Soc. (C) 1967. 12047etc.
The starting aldehydes of the formula II are con-verted to the corresponding acid chlorides by means of ~5 chlorine and/or a chlorinating agent; sulfuryl chloride or N-chlorosuccinimide being preferred. Chlorine or one of the cited chlorinating agents may be used per se, or 2 or more of the latter ones may be employed as mixture.
It is advantageous for the course of the reaction to use the reac~ants in a substantially stoichiometric ratio; however, the chlorinating agent may be present in excess.
As free radical forming agents there are used the compounds known for initiating radical reactions, such as organic~peroxides.~benzoyl peroxide etc.), or organic azo compounds (azo-bis-isobutyronitrile~. The free radical-forming agent is advantageously employed in catalytic : ~: .. , :, :
. . . . . : ~
..
, - 6 - ~OE 7g/F 201 amounts of from about 0.1 to 10 wei.ght ~, relative to the starting aldehyde II.
The reaction temperaturesare advantageously in the range of from about 20 to 150C, preferably from about 50 to 100C.
Suitable inert organic solvents are practically all those organic solvents in which at least the starting compound is soluble, and which react in no way neither with the starting compounds nor with the final products nor with the chlorinating agents and the free radical-forming agents. Preferred are chlorinated aliphatic hydrocarbons having from 1 to 4 carbon atoms, for example chloroform, carbon tetrachloride, hexachloroethane etc..
The ratio of solvents to the sum of the reactants may vary within relatively wide limits; generally, a weight ratio of from about 15:1 to about 3:1 of solvent to sum of starting aldehyde II and chlorinating agent is preferred.
Depending on the reaction temperature, the reaction time is from about 3 to 15, preferably about 3 to 10, hours.
In the reaction of 2,4,6-trihalopyrimidine-5-alde~
hydes with chlorine and/or one of the above chlorinating agent in accordance with the invention, first the corre-sponding acid chlorides only are formed, which can be rehalogenated, i~ desired, according to ~nown methods with usual fluorinating agents (anhydrous hydrofluoric acid, alkali metal fluorides, preferably NaF, KF or CsF, amrnonium fluorides, SbF3, SF4, K-fluorosulfinate etc.) 30 or brominating agents (PBr3 etc.) to give the corre- -sponding acid fluorides or bromides. In the case where the substituents y1~ y2 and/or Y3 are not the intended halogen, this rehalogenation may be continued until these substituents, too, are replaced by the intended ~ alo~.~n.~
In certai.n cases, for example when usinq PBr3, the rehalogenati.ng agent may serve as solvent for the re-halogenation.
:.: .;
, ~794~
,, ~
The reaction temperature for the rehalogenation sho~;ld be generally chosen in the range of from 20 to 250C, preferably 50 to 130C.
The 2,~,6-trihalopyrimidine-5-carboxylic acid hali-des of the above formula I in accordance with the inventionare interesting intermediates especially in the dyestuff field. For example, fiber-reactive dyestuffs are ob-tained by reacting the compounds of the formula I with amino group-containing dyestuffs according to the scheme indicated in German Offenlegungsschriften Nos. 2,113,298 and 2,208,972.
The following Examples illustrate the invention.
E X A M P L E
105.85 g (0.5 mol) of 2,4,6-trichloropyrimidine-5-aldehyde are dissolved in 500 ml anhydrous carbon tetra~chloride and, a~ter addition of 100 mg of azo-bis-iso-butyronitrile, heated to 60C with agitation. Subsequently r 67.48 g (0.5 mol) of sulfuryl chloride are slowly added dropwise. Thus, the solution is heated to boiling tempe-~0 rature, and viuorous de~elopment of hydrogen chlorideand sulfur dioxide starts. After a 4 hours' refluxing, furthe- 100 mg of azo-bis-isobutyronitrile and 6.75 g (0.05 mol~ of sulfuryl chloride are added, and refluxing is continued for another 4 hours. The light yellow solu-tion obtained is concentrated under reduced pressure, andthe yellow, partially crystalline residue is subjected to fractional distillation under reduced pressure.
Yield: 111.98 g of 2,4,6-trichloropyrimidine-5-carboxylic acid chlorida (91 w~%
of th.) b.p.: 73 - 76 at 1.63 mbar m.p.: 44 - 45C
E X A ~ P L E 2 105.85 g (0.5 mol) of 2,~,6-trichloropyrimidine-5 aldehy~e ~ 87.73 g (0.65 mol) of sulfuryl chloride in 500 ml of carbon tetrachloride are reacted as des-cribed in Example 1; however, the reaction time is pro-`' longed to 12 hours.
, I
, ~'7C3~
, - 8 - HOE 79/E~ 201 Yield: 117.52 g of 2,4,6-trichioro-pyrimidine-5-carboxylic acid chloride (96 Wt.~oL
th.) ' colorless crystals m.p.: 44 - 46C
21.15 g (0.1 mol) of 2,4,6-trichloropyrimidine-5-aldehyde are suspended in 100 ml of anhydrous carbon tetra-chloride. After having passed nitrogen through the sus-pension for 10 minutes, the batch is heated to 70C withagitation, 100 mg of benzoylperoxide are added, and 13.5 g (0.1 mol) of sulfuryl chloride are immediately added drop-wise, thus causing the reaction mixture to foam heavily.
After a 3 hours' agitation at reflux temperature (78C), the batch is allowed to cool, decanted from small amounts of precipitated solids, and the solvent is removed under reduced pressure. 16.72 g of a light yellow, semicrystalline mass is obtained. Distillation under reduced pressure gives 13.01 g of 2,4,6-trichloro-pyrimidine-5-carboxylic acid chloride, colorless crystals ~53 wt. %) b~p.: 73 - 76C at 1.6 mbar m~ 43 - 45C
4.92 g (20 mmols) of the 2,4,6-trichloropyrimidine-5-carboxylic acid chloride obtained according to Example 1 are agitated for 5 days at 110 - 120C with 75 ml of phos-phorus tribromide. The excess phosphorus tribromide is removed under reduced pressure, and the residue is sub-limated at 120 - 130C/0.15 mm.
Yield: 6.41 g of 2,4,6-tribromo-pyrimidine-5-carboxylic acid bromide m~.: 127 - 128C.
-2,4,6-trichlor~pyrlmidine-5-carboxyl~ acid bromide 21.15 g (0.1~moI')'`of '2,4,6-trichloro-pyrimidine-5-aldehyde, 19.58 g (0.1 mol) of N-bromosuccinimide and 100 mg of 2,2'-azo-bis-(2-methylpropionitrile) as chain .` " ~,, .`,. ,, ., ,,~!. -, . . .
initiator a~e suspended in 200 ml of ~nhydrous carbon tetrachloride, and heated for 3 hours to boiling tempe~
rature with agitation. After cooling, the solid succinimide is filtered off and the solvent is removed under reduced pressure. 34.1 g of crude acid bromide are obtained which are purified by distillation under reduced pressure.
Yield: 23.5 g (81 ~ of th.) of 2,4,6-trichloropyrimidine-5-carboxylic acid bromide mp.: 54 - 55C -b,p.: 84 - 90C at 0.35 - 0.4 mm IR: V = 1795 cm 1 -- c=o E X A M P I, E
.. . .
4,6-dichloro-pyrimidine-5-carboxylic acid chloride 14.85 g (0.11 mol) of sulfuryl chloride and 100 mg of 2,2'-azo-bis-(2-methylpropionitrile) as chain initiating agent are added to a suspension of 17.7 g (0.1 mol) of 4,6-dichloropyrimidine-5-aldehyde. Subsequently, the batch is heated to boiling temperature with agitation. After 3.5 hours, the vigorous development of hydrogen chloride and sulfur dioxide has come to an end. The clear, light yellow solution is liberated from the solvent under reduced pressure;22.5 g of crude acid chloride are obtained which are purified by distillation under reduced pressure.
Yield: 19.05 g (90.1 ~ of th.) of 4,6-dichloro-p~,rimi dine-5-carboxylic acid chloride b~p.: 60 - 62C at o.4 mm NMR (CDCl3): 8.9 ppm (1H, singulet) IR: VC=O = 1800 cm MS: molecular ~n m/e = 210 (3 Cl)
3~ -.... .. . . . . .
, , : . . :
" '~ ; ' .
: .
., . . , ~ . .
, , : . . :
" '~ ; ' .
: .
., . . , ~ . .
Claims (10)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A 2,4,6-trihalopyrimidine-5-carboxylic acid halide of the formula I
(I) wherein X, Y1, Y2 and Y3, independently from one another, are F, C1, Br.
(I) wherein X, Y1, Y2 and Y3, independently from one another, are F, C1, Br.
2. A compound as claimed in Cliam 1, wherein, in the formula I, X = Yl = Y2 = Y3.
3. A compound as claimed in Claim 1, wherein, in the formula I, X = Yl = Y2 = Y3 - C1.
4. A process for the preparation of a compound of the formula I as defined in Claim 1, in which a 2,4,6-trihalopyrimi-dine-5-aldehyde of the formula II
(II) wherein Yl through Y3 are as defined in Claim 1, is reacted whith chlorine, a chlorinating agent or a mixture of chlorine and a chlorinating agent, at a temperature of from about 20 to 150°C, in an inert organic solvent to form 2,4,6-trihalopyrimidine-5-carboxylic acid chloride and this compound may be rehalogenated with a fluorinating or brominating agent in order to obtain the fluoride or bromide, respectively.
(II) wherein Yl through Y3 are as defined in Claim 1, is reacted whith chlorine, a chlorinating agent or a mixture of chlorine and a chlorinating agent, at a temperature of from about 20 to 150°C, in an inert organic solvent to form 2,4,6-trihalopyrimidine-5-carboxylic acid chloride and this compound may be rehalogenated with a fluorinating or brominating agent in order to obtain the fluoride or bromide, respectively.
5. A process as claimed in Claim 4, in which in the 2,4,6-trihalopyrimidine-5-aldehyde of the formula II, Yl = Y2 = Y3.
6. A process as claimed in Claim 4, in which in the 2,4,6-trihalopyrimidine-5-aldehyde of the formula II, Y = Y = Y = Cl.
7. A process as claimed in Claim 4, Claim 5 or Claim 6 in which the process is carried out in the presence of a free radi-cal-forming agent.
8. A process as claimed in Claim 4, Claim 5 or Claim 6 in which the process is carried out at a temperature of from 50 to 100 °C .
9. A process as claimed in Claim 4, Claim 5 or Claim 6 in which the reaction is carried out in the presence of at least one member of the group of chlorine, sulfuryl chloride and N-chloro-succinimide.
10. A process as claimed in Claim 4, Claim 5 or Claim 6 in which the solvent is a chlorinated aliphatic hydrocarbon.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792929594 DE2929594A1 (en) | 1979-07-21 | 1979-07-21 | 2.4.6-TRIHALOGEN-PYRIMIDIN-5-CARBONIC ACID HALOGENIDES AND METHOD FOR THE PRODUCTION THEREOF |
| DEP2929594.1 | 1979-07-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1117943A true CA1117943A (en) | 1982-02-09 |
Family
ID=6076376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000356537A Expired CA1117943A (en) | 1979-07-21 | 1980-07-18 | 2,4,6-trihalopyrimidine-5-carboxylic acid halides and process for their preparation |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0023033A1 (en) |
| JP (1) | JPS5616472A (en) |
| CA (1) | CA1117943A (en) |
| DE (1) | DE2929594A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5371224A (en) * | 1992-11-24 | 1994-12-06 | Hoechst Aktiengesellschaft | Process for preparing 2,5-dibromopyrimidine |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA836241B (en) * | 1982-09-02 | 1985-03-27 | Ici Australia Ltd | Herbicidal cyclohexane-1,3-dione derivatives |
| US4507146A (en) * | 1982-12-28 | 1985-03-26 | Ciba-Geigy Corporation | 2,4-Diamino-6-halo-5-trifluoromethylpyrimidines having herbicidal activity |
| DE102007002674A1 (en) * | 2007-01-18 | 2008-07-24 | Bayer Cropscience Ag | Process for the preparation of substituted pyrazolecarboxylic acid chlorides |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1770049A1 (en) * | 1968-03-25 | 1971-09-16 | Bayer Ag | 4,5,6-trichloro-2-chlorocarbonyl-pyrimidine |
| DE2064096C3 (en) * | 1970-12-28 | 1979-04-05 | Bayer Ag, 5090 Leverkusen | Process for the preparation of 6-position substituted 2,4-dichloropyrimidine-S-carboxylic acid esters |
| DE2451630A1 (en) * | 1974-10-30 | 1976-05-06 | Bayer Ag | METHOD FOR PRODUCING TETRACHLOROPYRIMIDINE |
-
1979
- 1979-07-21 DE DE19792929594 patent/DE2929594A1/en not_active Withdrawn
-
1980
- 1980-07-17 EP EP80104172A patent/EP0023033A1/en not_active Withdrawn
- 1980-07-18 CA CA000356537A patent/CA1117943A/en not_active Expired
- 1980-07-18 JP JP9769580A patent/JPS5616472A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5371224A (en) * | 1992-11-24 | 1994-12-06 | Hoechst Aktiengesellschaft | Process for preparing 2,5-dibromopyrimidine |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0023033A1 (en) | 1981-01-28 |
| DE2929594A1 (en) | 1981-02-05 |
| JPS5616472A (en) | 1981-02-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5183492A (en) | Herbicidal 3-aryluracils | |
| US4748243A (en) | Preparation of 2-chloro-5-chloromethylthiazole | |
| EP0463464B1 (en) | Process for the preparation of 2-chloro-5-methylpyridine | |
| US4296034A (en) | Polyfluorinated sulfonamides | |
| CA1117943A (en) | 2,4,6-trihalopyrimidine-5-carboxylic acid halides and process for their preparation | |
| US3591601A (en) | N-chloro or bromo-2-oxazolidinones | |
| EP0553879B1 (en) | Process for producing 4-bromomethylbiphenyl compounds | |
| US3850920A (en) | N-halo-3-morpholinone | |
| US4727187A (en) | Process for the preparation of α, α-difluoroalkyl phenyl ether derivatives | |
| US5391733A (en) | Synthesis intermediates for 2-amino-6-halogenopurines | |
| US3408411A (en) | Manufacture of organic compounds containing fluorine | |
| US4668788A (en) | 5,5-dichloro-4,5-dihydro-6-hydroxy-2-trichloromethylpyrimidin-4-one | |
| US5352787A (en) | Process for the preparation of 5-(trifluoromethyl)-uracil, and the novel compounds 2,4-dichloro-5-trichloromethyl-pyrimidine and 2,4-difluoro-5-trifluoromethyl-pyrimidine | |
| KR0146349B1 (en) | Preparation of 5-amino-1,2,4,-triazole-3-sulfonamides | |
| EP0813515B1 (en) | Process for the preparation of esters of stilbenedicarbonic acid and process for the preparation of p-(chloromethyl)-benzoic acid | |
| US4220765A (en) | Process for the preparation of 4,6-dihalogeno-triazines | |
| CA1077482A (en) | 5-alkylsulphonyl- and 5-alkenylsulphonyl- barbituric acids and derivates thereof | |
| KR100676222B1 (en) | Process for preparing 4,6-dichloro-5-fluoropyrimidine | |
| JPH0853399A (en) | Preparation of aromatic fluorinated compound and new diamide | |
| US4140857A (en) | Process for the preparation of 2,4,5-trichloropyrimidine | |
| US3576804A (en) | Fluorotriazine compounds | |
| US5475165A (en) | Trifluoromethylation process | |
| US4419296A (en) | Preparation of tertiary alkyl cyanides | |
| EP0038223B1 (en) | Process for the preparation of trifluoromethylbenzoyl halides | |
| US4125723A (en) | Process for the preparation of tetrachloropyrimidine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |