Note: Descriptions are shown in the official language in which they were submitted.
~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 of5 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.
, ~ ` , ; ' ' ' ' ' '' '''...., ' : , ~ '
.' ' ,` ' '' . `' ' ` ~' ' ' , :
.
- 4 - HOE 79/F 201
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~
,, ~
- 7 - HOE 79/F 201
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
E X A M P L E 3
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
E X A M P L E 4
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.
E X A M P L E 5
-
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
.` " ~,, .`,. ,, ., ,,~!. -, . . .
- 9 - HOE 79/F 201
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~ -
.... .. . . . . .
, , : . . :
" '~ ; '
.
: .
., . . , ~ . .
