Note: Descriptions are shown in the official language in which they were submitted.
- 1 -
The present invention relates to a new process
for the preparation of new 3-isocyanato-1,2,5-oxadiazo(es
by reacting 3-amino-1,2,5-oxadia~oles or appropriate N'-
substituted 3-ureido-1,2,5-oxadia~oles wi~h phosgene at
temperatures between 150 and Z10C. The 3-isocyanato-
1,2,5-oxadiazoLes are useful ;ntermediate products in
organic chemical syntheses in many fields, for example
for the preparation o~ plant protection agents, medica-
ments, dyestuffs, etc.
The preparation of a large number of isocyanates
from the corresponding amines by reaction with phosgene
;s already known. It is also known that N-heterocyclic
compounds with an isocyanate group in the ~-posit~on are
unstable and tend to undergo spontaneous cycl;sation
15 react;ons (see Angew. Chem~ 80, 362 - 363 t1968)).
It has been found tha~ the new 3-isocyanato-
1,2,5-oxad;azoles of the general formula I
R ~ NCO (I)
in which
R represents an opt;onally substituted aromat;c
rad;cal, as defined below,
are obtained when compounds o~ the general formula II
N~-R1
~( (II)
in which
~10~
R has the mean;ng g;ven 2~ and
R1 represents hydrogen or the groups of the
general formulae III or IV
-CONH ~R (III)
Le A 22 942
-
65~7
23189-5939
-CONHR (VI)
in which
b41~
R has the meaning given ~be~e and
R denotes an optionally substituted aliphatic or arom-
atic radical, as defined below,
are reacted with phosgene at temperatures between 150 and 220C,
in the presence of an organic diluent, and the resulting isocyan-
ate of the general formula I is isolated by the customary methods
and, if required, purified.
In view of the prior art, it was surprising, and could
not be foreseen by a man skilled in the art, that it would be
possible to obtain the compounds of the general formula I in good
yield and high purity and in a simple manner by the process accord-
ing to the invention. With a knowledge of the prior art, it would
in fact have been expected that, under the reaction conditions to
be used according to the invention, any isocyanates formed would
to a substantial extent undergo decomposition or react further
to give undesired products, this taking place in the course of the
reaction (see Angew. Chem. 80, 362 - 363 (1968)). Under milder
conditions (such as lower temperatures and with the addition of a
base), the desired products are obtained only in unsatisfactory
amounts.
The optionally substituted aromatic radicals R and R2
of the above formulae contain 6 or 10 carbon atoms in the aryl
part. Optionally substituted phenyl or naphthyl, preferably
phenyl, may be mentioned as examples.
The optionally substituted aliphatic radical R2 repres-
ents optionally substituted straight-chain or branched alkyl having
- 2 -
5~37
23189-5939
1 to 12, preferably 1 to 8 and in particular 1 to 6, carbon atoms,
and optionally substituted cycloalkyl having 3 to 8, in particular
5 or 6, carbon atoms. Methyl, ethyl, n- and i-propyl, n-, i-, s-
and t-butyl and cyclopentyl and cyclohexyl may be mentioned as
examples.
- 2a -
587
-- 3 --
The aromatic radicals R and R2 and the aliphatic
radical R2 can carry one or more, preferably 1 to 5, in
particular 1 to 3 and particularLy pre-Ferably 1 or 2,
identical or different substituents~ Suitable substitu-
ents are all substituents which do not react with phos-
gene under the reaction conditions according to the in-
vention.
The following may be listed as examples:
halogen, preferably fluorine, chlorine, bromine and ;od-
ine, in particular fluorine, chlorine and bromine;~y~ having preferably 1 to 6, in particular 1 to 4,
carbon atoms, such as methyl, ethyl, n- and i-propyl, n-
;-, sec and tert.-butyl; ~ hav;ng preferably 1 ~o 6,
in particular 1 to 4, carbon atoms, such as methoxy,
ethoxy, n- and i-propoxy~ n-, i-, sec- and tert.-butoxy;
alkylthio having preferably 1 to 6, in particular 1 to 4,
carbon atoms, such as methylthio, ethylthio, n- and i-
propylthio, n-, i-, sec- and tert.-butylthio; C1-C4-
alkoxy-C1-C4-alkylthio; cyano; nitro; halogenoalk~ lo-
~ xy and ~ alky~ , each having preferably 1to 4, in particular 1 or 2 carbon atoms and preferably 1 to
5, in particular 1 to 3, halogen atoms, the halogen atoms
being identical or different and preferably be;ng fluor-
ine, chlorine and/or bromine, in particular fluorine and/
or chlorine, such as trifluoromethyl, trifLuoromethoxy,
trifluoromethylthio, chlorotrifluoroethoxy, difluorotri-
chloroethoxy, dichlorodifluoroethoxy, hexafluoro-n-pro-
poxy, chlorodifluoromethoxy and chlorodifluoromethylthio;
optionally halogen-substituted C~-C4-alkylcarbonyl,
C~-C4-alkoxycarbonyl, C1-C4-alkoxycarbonyl-C1-C2-
alkyl and C1-C~,-alkoxycarbonyl-C1-C4-alkyLthio;
C -C4-alkylene which is optionally substituted for
_1_
fluorine, chlorine and/or methyl and which is bonded to
the phenyl ring via two oxygen atoms; and phenoxy and
phenylthio~ ~here phenoxy and phenyl~h;o in turn can be
substituted as in the case of the aromatic radicals
Le A 22 942
~2~5~37
-- 4 --
R and R2~
R preferably represents phenyl ~hich can be sub-
stituted by halogen, nitro, cyano, C1-C~-alkyl~ C1-C4-
alkoxy, C1-C4-alkylthio, halogeno-C1-C4-alkyl, haLogeno-
C1-C4-alkoxy, halogeno-C1-C4-alkylthio, haLogeno C1-
C~-alkylrarbonyl, C1-C4-alkylcarbonyl, halogeno-C1-C4-
alkoxycarbonyL, C1-C~-alkoxycarbonyl, c1-C~alkoxycar-
bonyl-C1-C2-alkyl and/or C1 C4-aLkoxycarbonyl-C1-C4-
aLkylth;o.
R particuLarly preferably represents phenyL which
can be substituted by fluor;ne~ chLorine, bromine, cyano,
nitro, methyL, ethyL, methoxy, ethoxy, methylthio, tri-
fLuoromethyl, trifluoroMethoxy~ trifluoromethyLthio,
methyLcarbonyl, methoxycarbonyl, ethoxycarbonyL, n-butoxy-
carbonyL, tert.-butoxycarbonyL, methoxycarbonyLmethyL,
ethoxycarbonylmethyl, methoxycarbonylmethylthio and/or
ethoxycarbonylmethylthio.
R very particularly preferably represents phenyl
~hich can be substituted by fluorine, chlorine and/or
bromine.
R1 preferably represents hydrogen, the group of
the general formula III in ~hich R has the meaning given
above as being preferred, or the group of the general
formula IV in ~hich R2 denotes C1-C6-alkyl or phenyL.
R1 particularLy preferably represents hydrogen,
the group of the general formuLa III in which R has the
meaning g;ven above as being particularly preferred, or
the group of the general formula IV in which R2 denotes
C1-C4-alkyL or phenyl.
In the above definitions, unless stated otherwise,
haLogen denotes fluorine, chLorine, bromine or iodine,
preferably fLuorine, chLorine and bromine, in particular
fluorine or chLorine.
If 3-amino-40phenyl-1,2,5-oxadiazole is used as
a starting material (formula I, R = phenyl, R1 - H~, the
course of the reaction can be represented by the foLLo~-
Le A 22 942
:~4~i5~7
ing equation:
C6H5~1~N 2 COC12 ~NCO
If N-n-butyL-N'-(4-phenyl-1,2,5-oxacliazol-3-yl)-
urea (formula I~ R = phenyl, R1 = the group of the for-
mula IV in which R2 = n-butyl) is used as a starting
material~ the course of the reacti~n can be represented
by the following equation:
C6~5 ~CO
C6H5` ~ ~NH CO NH nC4Hg ~ \ ~ // ~ nC4H9-CNO
If N,N'-bis-(4-phenyl-1,2,5-oxadiazol-3-yl)-urea
~formuLa I, R1 = the group of the formula III in which
R = phenyl) is used as a starting material, the course of
the reaction can be represented by the following equation:
N ~, N IL~ " -4 HC1 ~' N
The 3-amino-1,2,5-oxadiazoles of the formula II
(R1 = H~ which are to be used as start;ng materials are
known and/or can be prepared by methods and processes known
from the literature (see J. Prakt. Chem. 315, 4, pages
791 - 795 (1973)).
Some of the oxadiazoles of the formula (II~ (R1
= a group of the formula lII) which are to be used as
starting materials are known and/or obtainable by custom-
ary methods. They can read;ly be prepared from, for ex-
ample, the compounds of the formula II (R1 = H) by the
reaction with phosgene at temperatures from 50 to 130C,
Le A 22 942
" ~465~7
-- 6
in an inert organic diluent, for example chLorobenzene.
The oxadiazoles of the formula II (R1 = a group
of the formula IV) which are to be used as starting mate-
rials are known or can be prepared by customary processes
5see J. Prakt. Chem. 315, 4, pages 791 - 793 (1973)).
AlL diluents customarily used for phosgenations
~an be employed as inert organic diluents. When the re-
action is ~carried out in an open system, the diluents
used are ~hose which have a boiling point in the range of
the react;on temperature ~hich can be used according to
the invention (150 to 220C) or ~hich have a ~oiling point
above this reaction temperature. ExampLes of sui~able
diluents are opt;onally halogenated aliphatic and aroma-
tic hydrocarbons, such as naphthalene, or benzene which
is substituted by alkyL and/or halogen, and naphthalene
or tetrahydronaphthalene or benzonitrile. o-Dichloroben-
zene is preferably used.
The process according to the invention is carried
out in a temperature range from 150 to 220C. It is pre-
ferably carried out at 160 to ~90C, particularly prefer-
ably at 160 to 180C. In special cases, it is also pos-
sibLe for the temperature to be above or beloh the stated
temperatures.
Depending on the apparatus employed, the process
according to the invention can be carried out under ele-
vated pressure, for example in an autoclave, or under
atmospheric pressure. In general, the reaction is car-
ried out under atmospheric pressure.
To carry out the process according to the inven-
tion, it ;s advantageous to employ at least 1 mol of phos-
gene per mol of starting material of the formula II in
which R1 = H or the group of the formula IV~ and at
least 2 mol of phosgene per mol of starting ma~erial of
the formula II in which R1 = a group of the formula III.
When the process is carried out in open systems, the
phosgene is passed continuously into the reaction mixture,
Le A 2? 942
_ 7 _ ~ 2 ~ ~5 8 7
so that in general an excess of phosgene is introduced.
In carrying out the process according to the in~
vent;on ;n open systems, the star~ing material of the for
~ula II is advantageously discolved or suspended in the
diluent. Phosgene is passed in and the reaction mixture
is brought to the desired reaction temperatures~ if appro-
priate ~hiLe stirring. The phosgene is passed in for
about 2 to 5 hours, while heating~ The optimum reaction
t;me for the particular reaction can readily be determined
in the customary manner. The diluent is then removed by
distillation, and the crude product obtained is puriFied
by distillation in vacuo.
The procedure in closed systems is carried out in
a correspond;ng manner. In this case, the required amount
of phosgene is added, under pressure, to the reaction
mixture, before the latter is heated.
As already stated above, the new compounds of
the general formula I constitute valuable intermediat~
products~ Surprisingly, the end products of the process
according to the invention are stable compounds which can
be stored and handled without problems.
The compounds of the general formula I can be
reacted with, for example, amines of the general formula V
R3 - NH2 (V)
in ~hich
R3 represents an optionally substituted aromatic
or heteroaroratic radical,
to give substituted furazanes of the general formula VI
R~ ~HCoNHR3
tVI)
~ ~ N
3D in which
R and R3 have the meanings given above.
To prepare the compounds of the general formula VI, for
example, molar amounts of the compounds of the formulae
I and V are reacted in dry toluene at temperatures of
Le A 22 ~42
~2g~58~
~ 8 --
approx. ~0C, and the solvent is removed by distillation
when the reaction is complete. The rompounds of the for-
mula VI remain behind as a solid mass.
For example, the following compounds o~ the for-
mula VI can be obtained in this manner:
Com- R R3 Melting
pound point tC)
_.__ _ ___ ___ ___
A1 Cl- ~ - ~ ~~ ~ -CF3 20B
~ o- ~ -CF3
The compounds of the formula VI have high acti-
vities against insects and spider mites and can therefore
be used as pest-combating agents in pLant protec~ion.
The acaricidal activity of the compounds of the
formula VI can be demonstrated by the following example:
Development_nhib;t;on test w;th Tetranychus urticae
(common spider mite)
Solvent: 3 parts by we;ght of dimethylformamide
Emulsifier: 1 part by ~eight of alkylarylpolyglycol ether
To produce a suitable preparation of active com-
pound, 1 part by ~eight of active compound is mixed with
the stated amount of solven~ and the stated amoun~ of
emuls;f;er, and the concentrate is diluted with water to
the des;red concentrat;ons~
The leaves of the bean plant (Phaseolus vulgar;s)
on which about 50 eggs of the common spider mite have been
deposited are immersed ;n the active compound preparation
of appropriate concentration. The total of destroyed
eggs, larvae, nymphs and dormant stages of a generation,
based on the number of eggs used, gives the destruction in
X. 100% means that all of the animals have been destroyed;
OX means that none of the animaLs have been destroyed.
In this test~ for example, the compounds A1 and A2
Le A 22 942
_ 9 ~
showed a destruct;on of 100X after 12 days at an active
compound concentrat;on of 0.02X.
The compounds of the formula VI can be formuLated
as solid or liquid pest-combating agents in the customary
manner by mixing w;th su;table carriers (for example
ground minerals or silica), diluents ~For exampLe dime-
thylformamide) and emuls;f;ers (for example dibutylnaph-
thalenesulphonate or cslcium dodecylbenzenesulphonate).
Appl;cation of these agents cnto the plants to be trea-
ted is carried out by dusting or spraying, if appropriateafter further dilution ~ith water.
The examples wh;ch follow are ;ntended to illus-
trate the process according to the invention (all percent-
ages are % by weight, unless stated otherwise).
Example 1
N~o
A mixture of 293 9 ~1.82 mol) of 3-amino-4-phenyl-
1,2,5-oxad;azole and 2 l of distilled o-dichlorobenzene
;s initially introduced ;nto a 4 l reaction vessel, and
the stirred mixture is heated rapidly to 160C~ During
th;s procedure, phosgene gas is passed in at above 60C
(approx. 100 g/h). At 160 - 165C, further phosgene is
passed ;n for 90 minutes, the ;nit;ally clear solution
becom;ng a suspension which is thick but stiLl readily
stirrable. The mixture is then heated under reflux, and
phosgene is passed in for 2.5 hours under reflu~, a clear
solution being formed. The m;xture is freed from phos-
gene by incip;ent distillation under atmospheric pressure,
and then evaporated down in a vacuum from a water pump.
The concentrate is distilled and redistilled, an oil pump
being used.
278 9 (82X of theory) of 3-isocyanato~4~phenyl-
1,2,5-oxadiazole having a boiling po;nt of 85C/0.1 mbar
Le A 22_942
-- ~2~i587
10 -
and a melting point of 53 - 54C are obtained by this
procedure.
__ 2
NCO
Cl- ~ ~
A mixture of 3~0 9 (1.53 mol) of 3-amino 4-(4'-
chlorophenyl)-1~2,5-oxadiazole and 2.6 l of distiLLed o-
dichlorobenzene are initially introduced in~o a 4 l reac-
tion vessel, and the stirred mixture is heated rapidLy
to 175C (reflux). During this procedure, phosgene gas
is passed in at above 60C (approx. 100 g/h~ The mix-
ture becomes clear a~ about 80C, and also remains clear
during the entire reaction. After phosgene has been
passed in under reflux for S hours, the mixture is freed
from phosgene by incip;ent distillation under atmospher;c
pressure, and then evaporated down ;n the vacuum from a
water pump. The concentrate is distilled in the vacuum
from an oil pump.
327 9 (96% of theory) of 3-isocyanato-4-(4'-chlo-
rophenyl)-1,2,5-oxadiazole having a boiling point of
87 - 88C/O.ûS mbar and a melting point of 66C are ob-
tained by this procedure.
Examples 3 - 9
The follo~ing compounds of the formula VII are
obtained by the procedure given in Examples 1 and 2:
~NCO (V I I )
Le A 22 942
___ _
587
Example Z Melt;ng Bo;ling po;nt
No. point ~C) b.p~/2 mbar (C)
3 2-C1 tO1-103
20
t3~ = 1,5646)*
4 2~Cl, 4-C1 67 1;25
4-F 80 83
6 4-Br 82 125
7 4-CH3 52105-~06
B 3-C1, 4-C1 40 132
9 4-SCF3 116
(~ = 1,5378)*
1G *Refractive index
Example 10
~ ~ ~ NC0
A suspension of 140 9 (Q.4 mol) of N,N'-bis-(4-
phenyl-1,2~5-oxadiazol-3-yl)-urea and 2 l of d;st;lled
o-dichlorobenzene are initially introduced into a 4 l re-
action vessel, and the stirred mixture ;s heated rap;dLy
to 160C, and then to 175C treflux) ;n the course of
1 hour. During this procedure, phosgene gas is passed in
at above 100C (approx. 100 g/h). Phosgene is then
passed in for another hour, under reflux, the mixture
slowly be;ng converted to a clear solution. The mixture
Le A 22 942
~4~
~ - 12 -
is then freed from phosgene by incipient distiLlation
under atmospheric pressure, after which it is evaporated
down ;n the vacuum from a water pump. The concentrate
is finally distilled in the vacuum from an oil pump.
After light ends t15.8 9 of dichlorobenzene and 7.2 9 of
3-isocyanato-4-phenyl-1,2,5-oxadiazoLe), 118 9 of 3-iso-
cyanato-4-phenyl-1,2,5-oxadiazole are obtained as the
principal fraction at a boiling point of 85G/0.1 mbar,
in the form of a colourless product~
Total yield: 125 9 ~ 83% of theory~
Melting point of the product: 53 - 54C.
Example 10 a (starting material for Example 10)
~NH-CO-NH ~
A mixture of 161 9 ~1.0 mol) of 3-amino-4-phenyl-
1,2,5-oxadiazole and 2 l of distilled chlorobenzene are
initially introduced into a 4 l reaction vessel, and the
stirred mixture is heated. Phosgene gas is passed into
the mixture (approx. 100 g/h)~ A colourless finely divi-
ded precipitate separates out above 60C. After 2 hours,
a temperature of 130C (reflux) is reached. Phosgene is
passed in under reflux for a further 30 minutes. The
readily stirrable ~uspension formed is freed from phos-
gene by ;ncipient distillation, and is then cooled and
filtered: N,N'-bis-(4-phenyl-1,2,5-oxadiazol-3-yl)-urea
is obtained in the form of 147 9 of virtually colourless
crystals of melting point 280C. By evaporating down
the filtrate, a further 21 9 of the product are obtained
in the form of brownish crystals of melting point 280C.
The product can be purified by recrystall;sation
from chlorobenzene. The colourless crystals ob~ained in
this procedure have a melting point of 280 - 281C.
The remaining ureas which can be used as starting
mater;als can be prepared similarly~
Le A 2? 942
12465B7
~ 13 -
Example 11
NC0
N~o ~N
52 9 (0.2 mol) of N-n-butyl-N'-(4-phenyl-1,2,5-
oxadiazol-3-yl)-urea (melting point 155C) are added to
400 mL of 0-dichLorobenzene~ and the mixture is heated
under reflux. During this procedure, phosgene is passed
in at a rate of approx. 100 g/h, until the urea has been com-
pletely converted (clear solution). After the excess phosgene
has been removed under reduced pressure, the solvent is dis-
tilled off together ~ith the n-butyl isocyanate, and the
residue is distilled in vacuo. 29 9 (77.4X of theory) of 3-
isocyanato-4-phenyl-1,2,5-oxadiazole (melting point 53 -
54C) were ob~ained at a boiling point of 82 -84C/2 mbar.
xample 12
~ ~ C0
56 9 (0.21 mol) of N-phenyl-N'-(4-phenyl-1,2,5-
oxadiazoL-3-yL)-urea (melting point 213C) in S00 ml of
o-dichlorobenzene are heated under reflux. Phosgene is
passed into the mixture at a rate of 1~0 g/h, until the
urea has been completely converted ~clear solution). The
excess phosgene is removed under slightly reduced pres-
sure, and the solvent and the phenyl isocyanate formed
are distilled off. In the subsequent distillation in
vacuo, 24 9 (64.2X of theory) of 3-isocyanato-4-phenyl-
1,2,5-oxadiazole (melting point 53 - 54C) are obtained.
The preparation of the insectidal and acaricidal
compounds of the formula VI can be illustrated by the
following example:
Le A 22 942
465~
- 14 -
Cl ~ ~ ,NH-C0-NH ~ 0 ~ CF3
(Compound A1)
2.53 9 (0.01 mol) of 4-t4-trifluoromethylphenoxy)-
aniline are d;ssoLved in 60 ml of dry toLuene at 60C~
After 202 9 (0.01 moL) of 3-isocyanato-4-(4-chLorophenyl)-
1,2,5-oxad;azoLe in 10 ml of dry toluene have been added,
the mix~ure is stirred for 30 minutes at 80C and the
bulk of the solvent is then distilled off. The residue
is separated off, and the product is then dried.
3.6 9 (76% of theory) of N-~4~(4-trifluoromethyl-
phenoxy)-phenyl~-N'-C4-(4-chlorophenyl)-1,2,5-oxadiazol-
3-yl)-urea of melting point 208C are obtained.
The remaining compounds of the formula VI can be
prepared according to this exampLe.
Le A 22 942
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