Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Process for preparinc., 1'd id'-c.arbonvidiazoies
The present invention relates to an improved process for preparing N,N'-
carbonyldiazoles by reacting azoles with phosgene.
It is already known that N,N'-carbonyIdiazoles caii be obtained by reacting
azoles
with phosgene (DE-B 10 33 210 and Liebigs Ann. Chem. 1957, 609, 75). In those
cases exclusively anhydrous tetrahydrofuran is used in the examples described,
with
a solution of the entire azole in anhydrous tetrahydrofuran being introduced
as the
initial charge, and then the phosgene bein- passed in.. The reaction takes
place at
room temperature. A striking feature is the low concentration of the azole in
the THF
solvent, of 2% to 4% by weight. In DE-B 1 033 210 it is stated only generally,
and
without any evidence, that instead of tetrahydrofuran it would in principle
also be
possible to use other ethers or aliphatic or aromatic hydrocarbons as
solvents. In a
process described in Chem. Ber. 1963, 96, 3374, similarly, the entire azole is
introduced in a THF/benzene solvent mixture and again only concentrations of
about
7% by weight of the azole in the solvent mixture are achieved.
According to a more recent process, that of EP-A-692 476, somewhat higber
concentrations of the azole in the solvent can be achieved in aromatic
solvents such
as benzene, toluene, xylenes, chlorobenzenes or mixtures thereof, which. are
each
dewatered by pa.rtial distillation prior to reaction, at temperatures of 50 to
120 C. A
description is given of concentrations in the range up to 12% by weight. In
this case
the solvent is first dewatered by partial distill.ation, then the azole is
added and
dissolved with heating, and then phosgene is passed in.
WO-A-00/14072 describes a process for preparing carbonyldiimidazole from
imidazole and phosgene at a temperature of 60 to 80 C which is carried out in
ortho-,
meta- or para-xylene, or mixtures thereof, or in chlorobenzene as solvent and
in
which the imidazole hydrochloride co-product obtained as a melt is separated
from
the resultant reaction mixture by phase separation at a temperature of more
than
100 C. The reaction per se is carried out by metering phosgene into the
initial charge
of imidazole solution.
DE-A-198 33 913 discloses a process for preparing N,N'-carbonyldiazoles which
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2
operates using arornatic solvents such as benzene, toluene, xylene or
chlorinated
benzenes wh.ich are dewatered beforehand by partial distillati.an..A. key
feature of this
process is that the azole, in sohÃtion in one of the aforementioned aronlatic
solvents,
and phosgene are inetered in parallel into a further, initial charge of
solvent. A
description is given of how by this type of process regime it is possible to
achieve an
azole concentration of up to 33% by weight. Since, however, a fraction of the
solvent
used is added together with the reactants, there is no possibility here of
subjecting the
entire solvent volume to azeotropic drying in the vessel intended for the
reaction.
Parallel metering is, however, in principle a technique which reduces the
economic
attractiveness of a process. In this specific case, reasonable filtration of
the azole
hydrochloride by-product only takes place if a very specific metering ratio is
observed precisely. The process, moreover, shows a sensitivity to
overphosgenation,
leading to a dark coloration of the resulting product.
Not only with the process of DE-A-198 33 913 but also with the other processes
described above that use aromatic solvents and run at temperatures of more
than
50 C there is a risk of the azole hydrochloride precipitate formed during the
reaction
being obtained as a viscous, sticky mass. This mass adheres solidly to vessel
walls
a.nd stirrer, making it much more difficult to stir the system. The difficulty
of the
stirring operation limits the maximum possible space/time yield to very low
levels. In
the case of solidification of the precipitate towards the end of the addition
of
phosgene, hard balls are formed which may, moreover, cause damage to the
reaction
vessel and its internals (e.g. stirrer, dip tubes, etc.).
There is therefore a need for an improved process for preparing N,N'-carbonyl-
diazoles with an extreniely simple process regime in which no tacky and
problematic
azole hydrochloride precipitates occur and, furthermore, no high reaction
temperatures are needed that would reduce the economics of the process as a
result
of high energy costs.
The invention provides a process for preparing N,N'-carbonyldiazoles of the
general
fornZula (I)
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CHS 04029_Fore.ign C:QUntri~s
0
/x
x N t '~' x 2
3 (1),
/c_x3 x C
RZ R2
where either
Xl, X2 and X3 independently of one another are each CR' or nitrogen, R' being
hydrogen or straight-chain or branched Ci-C6 alkyl, and
RZ is hydrogen,
or
Xl and X3 are CR1, the radical R' in Xl being hydrogen or straight-chain or
branched
Ci-C6 allcyl and the radical R' in X3 forming, together with R2, a
-CH=CH-CH=CH- bridge, and
X2 is CRl or nitrogen, Rl being hydrogen or straight-chain or branched
CI-C6 alkyl,
by reacting azoles of the general formula (ln,
xZ11ZXNH
c=x 3
R 2/
in which the radicals and synibols used have the definitions indicated for the
general
formula (1),
with phosgene, this process being characterized in that
(i) a halogenated aliphatic solvent from the group consisting of chlorinated
aliphatic hydrocarbons, brominated aliphatic hydrocarbons and mixedly
chlorine-/bromine-substituted aliphatic hydrocarbons is used and
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(ii) in that the entire arnount of azole to be reacted is introduced as an
initial
charge and then phosaene is metered in.
In the process of the invention, in contrast to the processes described in
EP-A-692 476, DE-A-198 33 913 and WO-A-00/14072, the azole hydrochloride
which precipitates during the reaction, such as the imidazole hydrochloride,
for
example, is fonned and remains continually as a readily stirrable, crystalline
precipitate which does not cake or stick to stirrer or vessel walls. Owing to
the
disperse nature of the precipitate, the stirring resistance is much lower than
in the
case of a non-inventive mode of operation. Surprisingly, in accordance with
the
invention, it is possible to obtain much higher reactant concentrations than
in the
case of the processes known to date, with a comparable non-parallel mode of
metering, which results in a significantly improved space/time yield as
compared
with the prior art: in the case of the processes of EP-A-692476 and WO-A-
00/14072
a reactant concentration of 11% and 1.1.9% by weight in the respective solvent
is
reported, respectively, whereas with the process of the invention reactant
concentrations of up to 25% by weight are obtained. It is also possible to
rule out
damage to the reactor and its internals as a result of hard azole
hydrochloride
conglomerates. Furthermore, the process of the invention possesses only very
slight
sensitivity to overphosgenation, which in other processes leads to
discoloration of the
isolated product. The quality of the N,N'-carbonyldiazoles thus obtained is
therefore
distinguished in particular by a very good Hazen colour number.
In the process of the invention it is possible to use either two different
azoles or else
only one single azole of the general formula (I1). In the first case an N,N'-
carbonyl-
diazole of the formula (I) is obtained in which the two azole rings are
different. In the
second case an N,N'-carbonyldia7ole with two identical azole rings is forzned.
This
second procedural variant is the preferred variant.
Preference is further given to using azoles in which in the general formulae
(I) and
(II) one or two of the moieties X1, X2 and X3 is or are nitrogen. Additionally
it is
preferred for X' to be CH, X2 to be nitrogen and X3 to be CR', R' and R2
together
fonning a -CH=CH-CH=CH- bridge.
Particular preference is given to using, in the process of the invention,
imidazole,
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benz.imidazole, pyrazole or 1,2,4-triazole as the azole of the general
fornnula (Il).
Very particular preference is giver, to irnidazol.e.
The said azoles of the general for-m.ula (1) are either available
comrnercially or else
are preparable by k-rrown processes of the prior art.
5 It is an essential feature of the process of the invention that the entire
amount of the
azole of the general fom7ula (li) to be reacted is introduced as an initial
charge in the
halogenated aliphatic hydrocarbon and then 0.2 to 0.3 mol, preferably 0.22 to
0.28 niol, more preferably 0.25 to 0.27 mol of phosgene is metered in per mole
of
azole of the general formula (lI). Phosgene can here be used in its usual
technical
grade.
The phosgene can be metered in continuously or semi-batchwise. Continuously
here
means that the phosgene is metered into the initial charge of azole/solvent
mixture
pennanently at a uniforzn rate over the entire reaction time. Semi-batchwise
means
that phosgene is metered into the azole/solvent mixture in portions,
distributed over
defined time periods.
The halogenated aliphatic solvent to be used originates from the group
consisting of
chlorinated aliphatic hydrocarbons, brominated aliphatic hydrocarbons and
mixedly
chlorine-/bromine-substituted aliphatic hydrocarbons.
As chlorinated aliphatic hydrocarbons it is possible for example to use
methylene
chloride, chloroform, 1,2-dichloroethan.e, 1,1-dichloroethane or 1,1,2,2-
tetrachloro-
ethylene.
As brominated aliphatic hydrocarbons it is possible for example to use
bromoform,
dibromomethane or 1,2-dibromoethane.
In addition it is possible to use hydrocarbons with mixed chlorine/bromine
substitution as solvents, such as 1-bromo-2-chloroethane, for example.
The halogenated aliphatic hydrocarbon from the abovementioned group that is
used
as solvent normally possesses a water content of not more than 0.5%,
preferably not
more than 0.2%, more preferably not more than 0.1 % and in particular not more
than,
0.05% by weight.
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1'Ialogenated aliphatic hydrocarbons with this wate- content are available as
solvents
either conllnercially or else by appropriate partial distillationidrying prior
to the
reaction according to the invention. The latter procedure is appropriate in
the process
of the invention. In this case it is possible to operate in two variants: on
the one hand
it is possible first to introduce the entirety of the solvent into the
reaction vessel and
to carry out partial distillation thereof for the purpose of drying to the
desired water
content. The entirety of the azole is added thereafter and the phosgene is
metered in.
On the other hand it is also possible for the entirety of the solvent to be
introduced
together with the azole in the reaction vessel and for the desired water
content to be
achieved by partial distillation of the azole/solvent mixture before the
phosgene is
metered in.
The process of the invention is normally carried out at a temperature in the
range
from 10 to 100 C, preferably at 20 to 80 C, in particular at 30 to 65 C.
In general it is advantageous, after the phosgene has been metered in, to stir
the
reaction mixture for a certain time, in the range from 30 minutes to 5 hours,
at the
same temperature.
In order to remove any excess phosgene present it is possible to pass nitrogen
gas
through the reaction mixture until phosgene is no longer detectable in the
outgoing
gas.
Likewise for the purpose of removing any phosgene excesses it is possible for
the
above-described solvent to be partially distilled until phosgene is no longer
detectable
in the reaction mixture.
The reaction mixture is worked up bv slurrying it from the reaction vessel
into a
filtration apparatus. Since the azole hydr.ochloride is in the form of a
crystalline
precipitate even after the end of the metered addition of phosgene, this
slurrying is
easy and complete. Then the azole hydrochloride precipitate fonned is
separated off
by filtration at 10 to 100 C, preferably at 20 to 80 C. This filtration as
well, owing to
the crystalline consistency of the precipitate, is accomplished effectively
and within
short filtration times. The N,N'-carbonyldiazole can be isolated from the
mother
liquor obtained during the azole hydrochloride separation by cooling the
mother
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-~-
liquor to -j!-40 to -70 C, preferably to <-25 to -20 C, and filtering off the
produ,r,t
which crystallizes out in the course of cooling. In this way the product is
obtained in
a well-crystallized form in purities of at least 90%, preferably at least 95%.
It is also possible to concentrate the mother liquor to cotnpletion following
the azole
hydrochloride separation and so to free it from the solvent. The N,N'-
carbonyldiazole
obtained in this way likewise already possesses a purity of at least 90%,
preferably of
at least 95%.
The economic attractiveness of the process of the invention can be enhanced if
the
mother liquor obtained after the crystallized N,N'-carbonyldiazole has been
separated off is recycled without further worlculg-up and is used as a basis
for the
phosgenation of further quantities of azole. This mother liquor may possibly
still
contain residual fractions of the N,N"-carbonyldiazole. Recycling the mother
liquor
in this way can be effected a number of times. Surprisingly, very good yields
and
high purities are still obtained, with no change, and in particular the N,N'-
carbonyl-
diazole obtained using recycled solvent continues to possess the excellent
Hazen
colour numbers.
A further improvement in the economic attractiveness can be achieved by
recovering
the quantity of azole obtained as azole hydrochloride in the process of the
invention.
This azole hydrochloride can be converted back into the free azole and so
recycled to
the reaction. In this way it is possible to achieve a doubling in the yield of
N,N'-carbonyldiazole, based on the azole employed.
The recovery of azoles from azole hydrochlorides can be carried out in
accordance
with DE-A-198 33 913, for example, by reacting the azole hydrochlorides
obtained
in the synthesis of the N,N'-carbonyldiazoles with. a compound of the formula
(III)
M(OR4), (III),
in which
n corresponds to the valency of M,
M is an alkali metal. or alkaline earth metal and.
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_g
R~ is hydrogen or CI-Cs alkyl.
This reaction takes place in a solvent mixture composed on the one lland of an
aromatic solvent such as, for example, benzene, toluene, a xylene, monochloro-
benzene, a dichlorobenzene, a trichlorobenzene or mixtures thereof and, on the
other
hand, of a solvent of the formula
R4 OH (IV),
in which
R4 has the definition indicated with respect to formula (III) .
In the formulae (IIl) and (IV) R4 is preferably hydrogen or methyl, and in
formula
(III) M is preferably lithium, sodium or potassium.
After the reaction of the azole hydrochloride with the compound of the formula
(III)
it is advantageous to distil off the entire compound of the formula (IV),
including the
compound of the formula (IV) formed during the reaction of azole hydrochloride
and
the compound of the formula (IIl), to remove the resulting salt MCh, by
filtration at
normal or elevated temperature, and to use the azole recovered, following
separation
of the aromatic solvent, for the N,N'-carbonyldiazole synthesis of the
invention.
This procedure goes particularly well if the compound of the formula (III)
used is
LiOH, NaOH or KOH in a solvent mixture composed of water (which is a compound
of the formula (IV) with R4 = hydrogen) and chlorobenzene, toluene, xylene or
2-metliyltetrahydrofuran and if the water is removed by azeotropic
distillation, for
example, by separating it off on a water separator, or else, if the compound
of the
fonnula (111) used is sodium. methoxide in a solvent mixture composed of
methanol
on the one hand and of chlorobenzene or xylene on the other, and if the
methanol is
separated off by distillation, by, for example, distilling it from the mixture
via an.
effective column.
In summary it is possible with the process of the invention, through the
reaction of
azole and phosgene using a halogenated aliphatic hydrocarbon solvent selected
from
the group consisting of chlorinated aliphatic hydrocarbons, brominated
aliphatic
hydrocarbons and mixedly chlorine- or bromine-substituted aliphatic
hydrocarbons,
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to prodtzce the azole hydrochloride by-prodt:ict reliably in a, non-tacky
consistency.
This a.liows the stirring properties of the reaction solutioit to be improved
and hence
allows higher concentrations of reactants and correspondingly higher
space/time
yields to be achieved. At the same time the easy removal of the azo
hydrochloride
from the reaction vessel is ensured, and dam.age due to hardened azo
hydrochlorides
is ruled out. The filtration times as well are surprisingly short by virtue of
the
improved filtration characteristics of the azole hydrochloride. A further
advantage of
the inventive use of a halogenated aliphatic solvent is the very low
sensitivity of the
reaction system to any excess of phosgene during or at the end of the
reaction: as
compared with prior art processes, both the consistency of the crystalline
azole
hydrochloride precipitate and the colour of the N,N'-carbonyldiazole obtained
from
the reaction mixture are affected little if at all by small excesses of
phosgene.
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Exain.ples
The Hazen colour nuniber is deterniined in accordance with ISO 6271.
Example 1 (inventive)
A. flask is charged with 531.5 g of dry dichloromethane and 93.8 g (1.37 mol.)
of
imidazole and this initial charge is heated to 35 C. At this temperature over
the
course of 1.75 hours 36.04 g (0.36 mol) of phosgene are added with an
introduction
rate of 20.6 g/h. The mixture thus obtained is subsequently stirred at the
same
temperature for 1.5 h.
In order to ensure a phosgene-free reaction mixture, 13.2 g of distillate are
taken off
under a pressure of 790 to 500 mbar and at 35-25 C, an
ammonia/water/isopropanol
mixttire is added to the distillate, and this mixture is discarded.
The imidazole hydrochloride by-product (isolated dry weight: 72.1 g) is
removed by
filtration at 35 C, the filter cake being washed with twice 100 ml of warm
dichloromethane at 33 C.
250.1 g of water-clear solution are distilled off from the combined organic
phases at
790 to 500 mbar and 35-25 C. The remaining solution is cooled to 0 C, and a
suspension forms. The precipitated carbonyl bisimidazole is separated off by
filtration and additionally washed with 50 ml of dichloromethane conditioned
to a
temperature of 0 C.
Drying of the crystals at 4 mbar and 30 C gives 40.0 g of product in the form
of
white crystals, Hazen colour number: 69.7. The purity of the product is 99.3%,
corresponding to a yield of 71.2% of theory.
Example 2(comparative in analogy to Example 1 from WO-A-00/14072)
In a flask, 68.22 g of imidazole are suspended in 505 g of xylene. The mixture
is
heated to reflux and dewatered by taking off 5 g of a xylene/water mixture.
The
temperature is reduced to 66 C and over the course of 30 minutes 25.2 g of
phosgene
are metered in with an introduction rate of 50.4 g/h.
After about 15 minutes the reaction mixture takes on a consistency like that
of
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chewing gum. When the metering of phosgene is at an end the ilnidazole
hydrochloride by-product is in the form of yellow valls. After a further hour
of
stirring at this temperature, this temperature is raised to 130 C, and the
consistency
of the imidazole hydrochloride changes to a brown melt.
The melt is drained off at 130 C. It solidifies on cooling to a dark-green,
solid mass.
The supenlatant xylene phase is cooled to 0 C. The precipitated crystals are
filtered
off and dried at 20 nibar and 50 C.
This gives carbonylbisimidazole in the fonn of white crystals with black
fractions
(Hazen colour number: 489). The purity is 96.8%, corresponding to a yield of
70% of
tlleory.
Example 3 (inventive)
A flask is charged with 375.2 g of dry chloroform and 93.8 g of imidazole and
this
initial charge is heated to 35 C. At this temperature over the course of 1.75
hours
35.02 g of phosgene are added with an introduction rate of 20.0 g/h. The
mixture
thus obtained is subsequently stirred at the same temperature for 1.5 h.
h1 order to ensure a phosgene-free reaction mixture, 28 g of distillate are
taken off
under a pressure of 280 mbar and at 30 C, an ammonia/water/isopropanol mixture
is
added to the distillate, and this mixture is discarded.
The imidazole hydrochloride by-product (isolated dry weight: 72.1 g) is
removed by
filtration at 35 C, the filter cake being washed with twice 100 ml of warm
chloroform at 35 C.
251.1 g of water-clear solution are distilled off from the combined organic
phases at
280 mbar and 30 C. The remaining solution is cooled to 0 C, and a suspension
forms. The precipitated carbonyl bisimidazole is separated off by filtration
and
additionally washed with 50 ml of chloroform conditioned to a temperature of 0
C.
Drying of the crystals at 6 mbar and 30 C gives 41.5 g of product in the form
of
white crystals having a Hazen colour number of 44. The purity of the product
is
99.5%, corresponding to a yield of 74.0% of theory.
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Exaannle 4 (inventive)
A flask is charged with 358.1 g of dry chloroforin and 119,36 g of imidazole
and this
initial charge is heated to 55 C. At this temperature over the course of 1.75
hours
44.57 g of phosgene are added with an introduction rate of 25.5 g/h. The
mixture
thus obtained is subsequently stirred at the same temperature for 2 h.
In order to ensure a phosgene-free reaction mixture, 5.4 g of distillate are
taken off
under a pressure of 630 mbar and at 35 C, an ammonialwater/isopropanol mixture
is
added to the distillate, and this mixture is discarded.
The iinidazole hydrochloride by-product (isolated dry weiglit: 96.0 g) is
removed by
filtration at 55 C, the filter cake being washed with twice 100 ml of wann
chloroform at 55 C.
The combined organic phases are cooled to 0 C, and a suspension forms. The
precipitated carbonyl bisimidazole is separated off by filtration and
additionally
washed with 50 ml of chloroform conditioned to a temperature of 0 C.
Drying of the residue at 4 mbar and 46 C gives 44.3 g of product in
crystalline form
having a Hazen colour number of 49. The purity of the product is 99.0%,
corresponding to a yield of 61.9% of theory,
Example 5 (inventive with recycling of the mother liquor)
1st ghoseenation
A flask is charged with 531.5 g of dry dichloromethane and 93.8 g(1.37 mol) of
imidazole and this initial charge is heated to 35 C. At this teinperature over
the
course of 1.75 hours 35.02 g(0.35 mol) of phosgene are added with an
introduction
rate of 20.0 g/h. The mixture thus obtained is subsequently stirred at the
sanie
temperature for 1.5 h.
In order to ensure a phosgene-free reaction mixture, 8.4 g of distillate are
taken off
under a pressure of 750 to 500 mbar and at 35-20 C, an
ammonia/water/isopropanol
mixture is added to the distillate, and this mixture is discarded.
The imidazole hydrochloride by-product (isolated dry weight: 80.3 g) is
removed by
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iltration at 35 C, the filter cake being wa.shed with twi:ce 100ml of warm,
dichlorometha.ne at 33 C.
The remaining solution is cooled to 0 C, and a suspension forms. The
precipitated
carbonyl bisimidazole is separated off by filtration and additionally washed
with
50 ml of dichloromethane conditioned to a temperature of 0 C. After the solid
carbonylbisimidazole has been filtered off, 553.0 g of mother liquor M 1 are
obtained.
Drying of the crystals at 5 mbar and 20 C gives 33.54 g of product in the form
of
white crystals with a Hazen colour number of 45.1. The purity of the product
is
99.6%: The yield therefore corresponds to 59.9% of theory.
2nd phosgenation
A flask is charged with 531.5 g of dichloromethane-containing mother liquor M1
from the lst phosgenation step and 93.8 g (1.37 mol) of imidazole and this
initial
charge is heated to 35 C. At this temperature over the course of 1.75 hours
35.02 g
(0.35 mol) of phosgene are added witli an introduction rate of 20.0 g/h. The
mixture
thus obtained is subsequently stirred at the same temperature for 1.5 h.
In order to ensure a phosgene-free reaction mixture, 21.6 g of distillate are
taken off
under a pressure of 750 to 450 mbar and at 35-20 C, an
ammonia/water/isopropanol
mixture is added to the distillate, and this mixture is discarded.
The imidazole hydrochloride by-product (isolated dry weight: 86.6 g) is
removed by
filtration at 35 C, the filter cake being washed with twice 100 ml of warm
dichloromethane at 33 C.
The remaining solution is cooled to 0 C, and a su.spension form.s. The
precipitated
carbonyl bisimidazole is separated off by filtration and additionally washed.
with
100 ml of dichloronlethane conditioned to a temperature of 0 C. After the
solid
carbonylbisimidazole has been filtered off, 553.0 g of mother liquor M2 are
obtained.
Drying of the crystals at 6 mbar and 30 C gives 39.4 g of product in the form
of
white crystals with a Hazen colour number of 33.2. The purity of the product
is
98.7%. The yield therefore corresponds to 70% of theory.
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1~+..
3!'d Uho5a2nation
A. flask is charged with 531.5 g of dichlorom.ethane-containing mother liquor
M2
from the 2nd phosgenation step and 93.8 g (1.37 mol) of imidazole and this
initial
charge is heated to 35 C. At this temperature over the course of 1.75 hours
35.02 g
(0.35 mol) of phosgene are added with an introduction rate of 20.0 g/h. The
mixture
thus obtained is subsequently stirred at the same temperature for 1.5 h.
In order to ensure a phosgene-free reaction mixture, 9.2 g of distillate are
taken off
under a pressure of 750 to 500 mbar and at 35-20 C, an
ammonia/water/isopropanol
mixture is added to the distillate, and this mixture is discarded.
The imidazole hydrochloride by-product (isolated dry weight: 88.1 g) is
removed by
filtration at 35 C, the filter cake being washed with twice 100 ml of warm
dichloromethane at 33 C.
The remaining solution is cooled to 0 C, and a suspension fonns. The
precipitated
carbonyl bisimidazole is separated off by filtration and additionally washed
with
100 ml of dichloromethane conditioned to a temperature of 0 C.
Drying of the crystals at 7 mbar and 20 C gives 37.3 g of product in the form
of
white crystals with a Hazen colour number of 41Ø The purity of the product
is
98.5%. The yield therefore corresponds to 65.9% of theory.
