METHODE DE PREPARATION DE 2,6-DICHLOROQUINOXALINE

PROCESS FOR PREPARING 2,6-DICHOLOROQUINOXALINE

Abrégé anglais

- 9 - HOE 89/F 249
Abstract of the disclosure
Process for the preparation of 2,6-dichloroquinoxaline
A process for the preparation of 2,6-dichloroquinoxaline
by hydrogenating 6-chloro-2-hydroxyquinoxaline-N-oxide in
aqueous sodium hydroxide solution in the presence of
about 0.001 to about 0.5 mol percent of a platinum shell
catalyst, relative to 6-chloro-2-hydroxyquinoxaline-N-
oxide employed, at temperatures of about 20 to about
120°C at a hydrogen pressure of about 1 to about 100 bar,
about 1 to about 3 equivalents of sodium hydroxide,
relative to 6-chloro-2-hydroxyquinoxaline-N-oxide
employed, being added, and after separating off the
catalyst from the hot solution depositing the 6-chloro-
2-hydroxyquinoxaline dissolved therein in the form of the
sodium salt as crystals by cooling the reaction solution
to a temperature of about 0 to about 20°C, drying azao-
tropically with an inert solvent and chlorinating using
a chlorinating agent in a customary manner to give 2,6-
dichloroquinoxaline.

Revendications

- 7 - HOE 89/F 249
Patent claims:
1. A process for the preparation of 2,6-dichloro-
quinoxaline which comprises hydrogenating 6-chloro
2-hydroxyquinoxaline-N-oxide in aqueous sodium
hydroxide solution in the presence of about 0.001 to
about 0.5 mol percent of a platinum shell catalyst,
relative to 6-chloro-2-hydroxyquinoxaline-N-oxide
employed, at temperatures of about 20 to about 120°C
at a hydrogen pressure of about 1 to about 100 bar,
about 1 to about 3 equivalents of sodium hydroxide,
relative to 6-chloro-2-hydroxyquinoxaline-N-oxide
employed, being added, and after separating off the
catalyst from the hot solution depositing the 6-
chloro-2-hydroxyquinoxaline dissolved therein in the
form of the sodium salt as crystals by cooling the
reaction solution to a temperature of about 0 to
about 20°C, drying azeotropically using an inert
solvent and chlorinating with a chlorinating agent
in a customary manner to give 2,6-dichloroquinoxaline.
2. The process as claimed in claim 1, wherein the 6-
chloro-2-hydroxyquinoxaline-N-oxide is hydrogenated
in the aqueous sodium hydroxide solution in the form
of the sodium salt in a concentration of about 15 to
about 30 percent by weight.
3. The process as claimed in at least one of claims 1
and 2, wherein the 6-chloro 2-hydroxyquinoxalin2-N-
oxide is hydrogenated in the aqueous sodium
hydroxide solution in the form of the sodium salt in
a concentration of about 20 to about 25 percent by
weight.
4. The process as claimed in at least one of claims 1
to 3, wherein the 6-chloro-2-hydroxyquinoxaline is
deposited in the form of the sodium salt as crystals
by cooling the reaction solution to a temperature of

- 8 -
about 5 to about 10°C.
5. The process as claimed in at least one of claims 1
to 4, wherein the sodium salt of the 6-chloro-2-
hydroxyquinoxaline is chlorinated using thionyl
chloride, phosphorus pentachloride, phosgene or
phosphorus oxychloride.
6. The process as claimed in at least one of claims 1
to 4, wherein the 6-chloro-2-hydroxyquinoxaline is
isolated in high purity by acidifying the deposited
sodium salt of the 6-chloro-2-hydroxyquinoxaline or
an aqueous solution of this compound with a mineral
acid.

Description

2 ~ 6 4
HOECHST AXTIENGESELLSCHAET ~OE 89/F 249 Dr. .~U/rh
Description
Proces~ for the preparation of 2,6-dichloroquinoxaline
The invention relates to an Lmproved process, compared to
the prior rt, for the preparation of 2,6-dichloro-
quinoxaline by reduction of 6-chloro-2-hydroxy-
quinoxaline-N-oxide to 6-chloro-2 hydroxyquinoxaline,
crystallization of its sodium salt, removal of the water
and chlorination in a manner known per se.
2,6-Dichloroquinoxaline is an important precur~or for the
pr~paration of plant protection agent~ (EP 276,741A; DE-
OS 3,004,770). In this connection, it is important that
the 2,6-dichloroquinoxalino i~ employed in pur~ form.
All known proces-~es for the preparation of 2,6-dichloro-
quinoxaline (cf.EP0,295,815; EP0,295,797; USP4,636,S62,
Sakata et al., Heterocycles 23, 143, 2025 (1985); DE
3,901,406; European Patent Application 89 106 784.5, in
combination with Houben-Weyl, vol. VIII, 359 et seq.
(1952), or Organikum, Berlin 1975, VEB Deutscher Verlag
der Wissenqcha ten) lead ~o a product whose quality is
insu ficient for immediat~ furthor proc2~ing to the
plant protection agon~ and to other product~, which is
why the 2,6-dichloroquinoxaline obtainable by the known
proce~o3 ha~ to b0 sub~ected to compli~ated purification
stEps before further proce~sing. There was thu~ a need
for a preparation proce~s in which tho 2,6-dichloro-
quinoxaline is obtainod in ~uch a high d~gree of purity
th~t it ca~. ba further proc~ssed to the d~ired ~inal
product Lmmadiately without complic~ed purifica~ion
operation~.
It ha~ now urpri3ingly b~en found that 2,6~dichloro-
quinoxaline can be pr~pared in a high degre~ o~ purity
and at the 3ame ti~0 in Y~ry good yiold by hydro~enating
6-ch}oro-2~hydroxyquinoxalin0-N-o~id~ in ~queou~ ~odium
hydroxide ~olution in thQ preLq0nce of about 0.001 to

2 ~ 6 4
-- 2 --
about 0.5 mol percent, preferably 0.01 to about 0.05 mol
percent, of a platinum shell catalyst, relative to 6-
chloro-2-hydroxyquinoxaline-N-oxide employed, at tempera-
t~res of about 20 to about 120C, preferably of about 60
to about 100C, at a hydrogen pressure of a~out 1 to
about 100 bar, preferably of about 5 to about 20 bar,
about 1 to about 3 equivalent~ of sodium hydroxide,
relative to 6 chloro-2-hydroxyquinoxaline-N-oxide
employed, being added, after separating off the catalyst
from the hot solution depositing the 6-chloro-2-hydroxy-
quinoxaline dissolved therein in the form of the sodium
salt as crystals by cooling the reaction solution to a
temperature of about 0 to about 20C, preferably about 5
to about 10C, drying azeotropically u3ing an inert
solvent and chlorinating with a chlorinating agent in a
manner customary per se to give 2,6-dich~oroquinoxaline.
In the proce~ according to the invantion, the following
may be carried ol-t in particular:
As a rule, it i~ expedient to ~ub~ect the 6-chloro-2-
hydroxyquinoxaline~N-oxide to the hydrogenation in
suspen~ed form in the aqueous 30dium hydroxide 301ution
in a concentration of about 15 to about 30 pexcent by
weight, preferably of about 20 to about 25 percent by
weight.
Depending on the reaction para~e~ers, the catalytie
hydrog~nation take3 about 30 minu~e~ to about 5 hour~, a~
a rule about 1 to about 3 hour3.
Shell cataly~t~ are designa~ed as tho~e hydrogena~ion
cataly.Rt~ in which the noble m~t~l, for example platinum,
i~ di~tributed in extremQly fine form pxQdo~ina~tly on
the surface of a ~upport ma~erial p~r~icl~, for example
active carbon, in contra~t to the co~monly designated
noble metal cat ly~t3 which h~ve a pr~dominantly uniform
di~tribution of th~ noble m~tal also inside (via pore~

2~6456~
-- 3 --
etc.) of a support material particle.
The catalyst employed can be employed repeatedly.
The sodium salt of the 6-chloro-2-hydroxyquinoxaline
formed by the hydrogenation is present under the reaction
conditions in dissolved form and can be separated off
from the catalyst in a sLmple manner. On subsequent
cooling to about 0 t~ about 20 DC t preferably about 5 to
about 10C, it precipitates out virtually quanti~atively.
~he product thus obtained is of excellent quality.
For further processing, it is added, preferably in water-
moist form, to an inert diluent which can form an azeo-
trope with water. Suitable diluents which may be men-
tioned are, for example, benzene, toluene, xylenes (all
isomers and their mixture~), cumene, chlorobenzene,
1~ ethylbenzene, carbon tatrachloride, trichloromethane,
cyclohexane, hexane, heptane and suitable petroleum ether
fractions. The water prQsent is then separated off
azeotropically.
The product is ~ubsequently chlsrinated in a manner known
per se uQing one of the customary chlorina~ing agent~,
such as, for example, thionyl chloride, pho3phorus
pentachloride, pho3gene or preferably pho~phoru3 oxy-
chloride (se~, for example, Houben-Weyl, vol. VIII, 359
et ~eq. (1952~; Organikum, ~erlin 1986, VEB DQut~char
Verla~ der Wi son~chaften).
The chlorinating agen~, which i3 2mployed in exces~
separated o~f and can be used for further bat~he3 t just
lik~ the diluent which can be recover~d again.
Working-up i8 carried out in a cuetomary manner. The
final product~ 2,6~dichloroquinoxaline, i~ obtained in
the required high purity and a~ditionally in ~ery good
yi01d .

2~56~
-- 4 --
It is in this respect to be consider~d surprising that
the sodium salt of the 6-chloro-2-hydroxyquinoxaline can
be caused to deposit in crystalline form virtually
quantitatively according to the invention, as it is
S ntrinsically very easily soluble both in the presence of
heat and also on relatively high dilution.
The extreme purification effect associated with the
virtually quantitative crystalline deposition of the
sodium salt of 6-chloro-2-hydroxyquinoxaline achieved is
to be judged as particularly surprising, since owing ~o
its low solubility in the customary ~olvent~, even at
relatively high temperature, and the great YLmilarity to
the relevant impurities, rec~ystallization of the neutral
6-chloro-2-hydroxyquinoxaline is ~u~t as ~atisfactory as
recrystallization of the subsequent ~tage ~2,6-dichloro-
quinoxaline) synthesized under con~entional condition~.
In addikion to advantage of the process according to the
invention already mentioned further above, there is a
further Lmportant advantage, in particular from the
ecological point of view, in the great reduction ~f the
salt load of the total procesq a~ a result of the omis-
sion of an intermediate i~olation of the 6-chloro-2-
hydroxyquinoxalina ~ormsd as an intermediate and the
neutralization as30ciated therewith.
If it i~ de~ired to recovor the 6-chloro-2-hydroxy-
quinoxaline obtained at the end of the hydrogenation step
in a high degree of purity and in ve~y good yield a~ such
in pure form, it can be obtained pure in a simple m~nn2r
by adding a mineral acidr 3uch a~, ~ox exæmpl~, ~ulfuric
or hydrochloric acid9 to the depo~ited ~odium salt of ~he
6-chloro-2-hydroxyquinox21ine or prefexably to an a~ueous
~olution of this compound.
The axample below erve to illu~rata ~ha process
according ~o the invention, withou~ lLmi~ing i~ thereto.

~ o ~
-- 5 --
E~ample
593 g (l mol) of 6-chloro-2 hydroxyquinoxaline-N-oxide
sodium salt in industrially moist form were suspended in
757 g of water and heated to 80 - 90~C in the presence of
2 g of platinum shell catalyst ~type ~.5 Pt/C, F 101 KY/W
containing about 50 percent by weight of water (DEG~SSA))
and hydrogenated in an autoclave using hydrogen under a
pressure of 10 bar for 1.5 hours. The catalyst was
subs~quently separated off at 80 - 90C by means of a
pressure filter, the filtrate was cooled to abou~ 5C and
the precipitat~ was filtered off through a filter.
369.5 g (0.9 mol) of 6-chloro-2-hydroxyquinoxaline were
obtained in the form of the sodium salt as a moist
product.
I~omeric chlorohydroxyquinoxalines were not detectable,
and 6-chloro-2,3-dihydroxyquinoxaline or its sodium salt
were only detectable in the smallest traces (in each case
by HPLC, qualitativs).
A dried ~ample of the sodium salt howed the following
analytical ddta:
C: 42.0 %; H: 2.7 %; N: 12.0 %; O: 12.9 %;
Cl: 15.2 %; Na: 10.2 %.
Purity about 89 ~ (HPLC: ext. standard)
164.2 ~ (0.4 mol) of the moi~t product were then su~pen-
ded in about 700 ml of xylena and dried azeotropically,and 245.0 g (1.6 mol) o~ pho~phoru~ oxychloride were
added under reflux. Af~er stirring for a fur~her
30 minute~, the exces~ chlorinating agent wa3 removed by
distillation, the re~iduo wa~ diluta~ with abou~ 290 ml
of xylene, and the mixture wa~ neu~ralized, clarified
whilo hot and ~read from ~olYent by s~eam di~tillation.
~he product which crystallized out was fil~er~d off with
suction and dried.
72.2 g of 2,6-dichloroquinoxalln~ having a puri~y of