Note: Descriptions are shown in the official language in which they were submitted.
~2496(~1
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23189-6151
The invention relates to a new process for the
preparation of substituted phenylhydrazines uhich can be
used as intermed;ate products for the synthesis of herbi-
cidal active compounds.
It is a~ready known that substituted phenyLhydra-
zines are obtained when substituted anilines are first
diazotised with sodium nitrite in the presence of an acid
and then reduced in a second stage, for example ~ith tin-II
chloride, aqain in the presence of an acid Scompare, for
example, Houben-~eyl, "Methoden der organischen Chemie"
~"Methods of Organic Chemistry"), Yolume X, 2; page 203,
Thieme Verla~ Stuttgart 1967).
The d~sadvantage of this process is that the yield
and purity of the reaction products thus obtainable is
often not satisfactory, a fact uhich ;s due on the one hand
to the general disadvantages of a multi-stage reaction
method and on the other hand ;t is also attributable to
special problems in both stages. Thus, for example, the
preparation of the diazonium salts ~1st stage), uhen using,
as start~ng compounds, anilines ~ith hydrophobic substitu-
ents, often succeeds only poorly in the required aqueous
med1um. A further difficulty in the diazotisation is that
side-reactions, such as, for example, azo coupling, are
possible and do also occur. The reduction of the diazonium
salts ~2nd stage) also often does not take place completely,
and this again contributes to contamination and lo~ering of
yield.
It has b-en found that cubstituted phenylhydrazines
of the formula (S)
R1 Cl
R3-(X)n ~ NH-NH2
~I)
~2 Cl
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in uh;ch
R1 and R2 represent hydro~en or chlorine,
R3 represents halogenoalkyl,
X represents oxygen, sulphur, sulphinyL or sulphonyl
and
n represents a number 0 or 1,
are obtained ~hen substituted chlorobenzenes of the for~ula
~II)
R1 Cl
R3-¦X)n ~ -Cl ~II)
R Cl
in ~hich
R~, R2, R3, X and n have the abovementioned
meanings~
are reacted ~ith hydrazine or hydrazine hydrate in the pre-
sence of a diluent, if appropriate under elevated pressure,5 at temperatures between 60C and 160C.
It must be regarded as distinctly surprising that
~ith the aid of the process according to the invention the
desired substituted phenylhydrazines are obtained in h;gh
yields and good purity, since according to the state of the0 art it uas not to be expected that, ~iven that in the
starting product of the formula ~II) there are at least
three chlorine atoms available for the substitution reac-
tion according to the invention, only one product ~ould be
formed selectively.
The process according to the invention has a number
of advantages. These include, for examp~e, the single-
stage reaction method in an organic so~vent, ~hereby so~u-
bility problems ~hen using hydrophobic starting materials
are avoided. The expensive isolation of intermediate pro-
ducts is a~so avoided. ~ further advantage of the process
according to the invention is the easy accessibil~ty of the
substituted chlorobenzenes of the formula ~II) uhich can be
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used as starting compounds.
~ith the aid of the process according eO the inven-
tion, there are preferably obtained those substituted
phenyLhydrazines of the formula (I)
5 in ~h;ch
R1 and R2 represent hydrogen or chlorine,
X represents oxygen, sulphur, sulphinyl or sulphony~,
R3 represents straight-chain or branched halogeno-
a~kyl ~ith 1 to 4 carbon atoms and 1 to 9 identical
or different halogen atoms and
n represents a number 0 or 1.
Particularly preferentially, there are obtained
compounds of the formula ~)
in ~hich
R1 and R2 represent hydrogen or chlorine,
R3 represents difluoromethyl, trifluoromethyl,
trichloromethyl, dichlorofluoromethyl, difluoro-
chloronethyl, trifluoroethyl, tetrafluoroethyl,
pentafluoroethyl, tetrafluorochloroethyl, tri-
fluorochloroethyl, trifluorodichloroethyl, di-
fluorotrichloroethyl, difluorotriohlorocthyl, di-
p~ fluorodichloroethyl, tetrachlorofluoroethyl or
pentachloroethyl,
X represents sulphur, sulphinyl or sulphonyl and
2S n represents a number 0 or 1.
Ifo for example, 1,2,3-trichloro-5-trifluoromethyl-
benzene and hydrazine hydrate are used as starting mater-
ials, the course of the reaction in the process accordin~
to the invention can be represented by the follo~ing
30 equation: ~
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12~g601
J:l
2N-N~2 ~ ~ase
-~Cl
Cl
fl
F3C ~ -NH-N~2
The formula ~II) provides a general definition of
the substituted chlorobenzenes required as starting mater-
ials for carry;ng out the process according to the inven-
tion.
Preferred compounds of the formula ~II) are those
in ~h~ch R1, R2, R3, X and n represent those radicals
~hich have already been ment;oned as preferred for these
subst;tuents and ind;ces in the context of the description
of the end products of the formu~a tI).
The substituted chlorobenzenes of the formula ~II)
are knoun (compare, for example, DE-OS ~German Published
Specificat;on) 2,644,641; DE-OS (German Publ;shed Specifi-
cation) 2,333,848; Japanese Patent 49/2108; J. Fluorin*Chem. 9, 113-126 ~1977); Ind. Eng. Chem. 39, 378-380 ~1947))
or can be prepared analogously to processes knoun in prin-
ciple. The process according to the invention can, ;f
des;red, be carried out in the presence of a suitable
diluent. PrefPrably, diluents are used in the process
according to the ;nvent;on.
Suitable diluents are v;rtually all inert organ;c
so~vents. These in particular include polar or dipolar
aprotic solvents such as a~cohols, for example methanol,
ethanol, n- or i-propanol or ethylene glycol, or ethers,
such as, for example, dioxane, d;methoxyethane or d;ethyl-
ene glycol d;methyl ether, or sulphox;des, such as, for
example, d;methylsulphox;de. Part;cularly preferred dilu-
ents are dioxane and n-propanol.
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lZ4~601
Further particularly preferred di~uents are ~eakl~
basic solvents, such as, for example, pyridine.
The process accordinq to the invention is in
general carried out at temperatures betueen ~60C and
~160C. The temperature range of bet~een ~80C and ~140C,
especially betueen ~100C and 120C, is preferred. The
reactions are ;n general carried out under normal prcssure.
Ho~ever, depending on the boiling point of the di~uent used
it can also be of advantage to appl~ the pressure required
to reach the requisite reaction temperature. In these
cases, the process is in general carried out in the pres-
sure range of from 1 to 30 bar, preferably from 1 to 20 bar.
To carry out the process according to the inven-
tion, 1.0 to 10.0 moles, preferab~y 2.0 to 8.0 ~oles,
especially 3.0 to 7.0 moles, of hydrazine or hydrazine
hydrate are in general emp~oyed per mole of substituted
chlorobenzene of the formula ~II).
The reaction is carried out by heating the reac-
tants, dissolved in the appropriatc diluent, to the requi-
site reaction temperature for 8 to 60 hours (the course of
the reaction during this time can be folloued by, for
example, gas chromatography); uhen using lou-boiling dilu-
ents it ~ay be necessary to uork under pressure in order to
reach the required reaction temperature.
For uorking up, the solvent is distilled off~ the
residue is taken up in uater, the mixture is brought to
pH 10 uith aqueous sodium hydroxide solution and the pro-
duct is extracted ~ith a ~ater-immiscible solvent. The
combined organic phases are, if necessary, a~ain uashed
~ith concentrated aqueous sodium chloride solution, dried
and concentrated in vacuo.
The crude products of the formula ~I), thus
obtained, can either be purified by distillation or be
crystallised from a suitable solvent, such as, for example,
n-hexane.
The substituted phenylhydrazines of the formula ~I)
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23189-6151
are valuable intermediate products and are suitable, for example,
for the synthesis of herbicidally active 5-acyl-amino-1-phenyl-
pyrazoles, which are described, for example, in German published
patent applications DE-OS 3,402,308 or DE-OS 34 20 985.9.
Thus, new 5-aminopyrazoles of the formula (III)
~ NH2
¦ (III)
C ~ ~ Cl
R ~ R
tX,)n
R
in which
R4 represents cyano or alkylaminocarbonyl and
Rl, R2, R3, X and n have the abovementioned meaning
are obtained when acrylonitrile derivatives of the formula (IV)
~ CN
C2H O-CH=C R4 (IV)
in which
R4 has the abovementioned meaning
and phenylhydrazines of the formula (I)
/
R3-(X)n ~ NH-NH2 (I)
R Cl
in which
R , R2, R3, X and n have the abovementioned
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12~9601
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meaning
are either initially reacted in a first stage, if approp-
riate in the presence of a diluent, such as, for exampLe,
glacial acetic acid or ethanol, and, if appropriate, in the
presence of a reaction assistant, such as, for exanple,
sod;um acetate, at temperatures bet~een -20C and ~20C,
to give the phenylhydrazine derivatives of the formula CV)
R Cl
~3-lX~ H-CH=C ~ (V)
in uh;ch
R~, R2, R3, R~, X and n have the abovement;oned
meaning
these then being cyclised in a second stage, if appropriate
in the presence of a diluent, such as, for example, ethyl-
ene ~lycol monoethyl ether, at te~peratures betueen ~50C
and ~150C, or are directly cyclised in a single reaction
step, ~ithout isolation of the intermediate stage of the
formula ~V), if appropriate in the presence of a diluent
such as, for example, ethylene glycol monoethyl ether or
ethanol, at temperatures bet~een ~50t and ~150C.
~he acrylon~trile derivatives of the formula ~IV)
are knoun ~compare European Patent 34,945 or DE-OS ~6erman
Published Specification) 3,129,429).
Neu herbicidally active substituted 5-acylamino-1-
phenylpyrazoles of the formula ~VI)
_____,R4
~`N ~ ~-CO-R
Cl ~ Cl ~VI)
R~Rt
(X)
,3n
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124~960~
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in ~hich
R1, RZ, R3, R4, X and n have the abovementioned
meaning and
R5 represents hydrogen, or alkyL, alkenyl or
aLkinyL, or opt;onaLLy substituted cycLoalkyL, or
alkoxyalkyl, alkylthioalkyl or halogenoalkyl, or
optionally substituted aryl
are obtained uh~n 5-s~inop~ra~oLes of the formuLa tI~I)
R4
N~N NH2 ~III)
Cl ~ Cl
R
(X)n
R
in which
R1, R2, R3, R4, X and n have the abovementioned
meaning
are reacted ~ith acyLating agents of the formuLa tVII)
R5 - C0 - A (VII)
15 in which
R5 has the abovementioned meaning and
A represents an ac~ivating leaving group, such as,
for exampLe, haLogen, or a radicaL R5-Co-o,
wherein
2û R5 has the abovementloned meaning,
if appropriate in the presence of a d;Luent, such as, for
exampLe, chLoroform, and, if appropriate, ln the presence
of an acid acceptor, such as, for example, triethyLamine,
at temperatures between -20 and +150C.
~o carry out this process, in general 1 to 20 moles,
preferabLy 1 to 15 moLes, of acyLating agent of the formula
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124~601
_ 9 _
(VII) snd, in general, 1 to 3 mo~es, preferabLy 1 to 2
mo~es, of acid acceptor are employed per mole of S-amino-
pyrazoLe of the formula ~III). The conduct of the reaction,
uorking up and isolation of the end products of the formula
~VI) are performed in the customary manner. The acylating
agents of the formula ~VII) are generally kno~n.
PrcParation Exaoples
Example 1
~3C~NH-NH2
Cl
6.2 ~ ~0.025 ~ole) of 3,4,5-trichloro-trifluoro-
methylbenzene and 6.25 9 ~0.125 ~ole) of hydrazine hydrate
in 12 ml of pyridine are heated at 115-120C, under reflux,
for 48 hours. To uork up the nixture, the solvent is dis-
tilled off, the residuc is taken up in uater and three
extractions, each with about 30 ml of methylene chloride,
are carried out. The combined organic phases are dried
over magnesium sulphate, concentrated in vacuo and then
distilled.
5.1 9 ~83X of theory)of 2,6-dichloro-4-trifluoro-
~ethylphenylhydrazine, of meltin~ point 56 - 57C, are
obtained, the naterial being 90X pure as determined by gas
chromatography.
Example 2
C ~
~ 3C-~_NH_NH2
C ~ _
200 9 (0.704 mole) of 2,3,4,5-tetrach~oro-tri-
fluoromethylbenzene and 24û ml (247.2 9/4.94 moles) of
hydrazine hydrate in 500 ml of dioxane are heated at 100-
105C, under reflux, for 14 hours. The heavy ~aqueous)
phase is separated off from the cooled t~o-phase reaction
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124~6(~
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m;xture and the or~anic phase is concentrated to dryness
in vacuo. The residue is suspended in 600 ml of water and
100 ml of methylène chloride, the pH is brought to 10 ~ith
10X strength aqueous sodium hydroxide solution, and the
mixture is slowly heated to bet~een 30C and 35C, in
the course of ~hich t~o clear phases form from the cloudy
suspension. The nixture is alloued to cool to roon tem-
perature, the organic phase is separated off, ~ashed ~;th
200 ml of concentrated aqueous sod;um chlor;de solut;on
and dried over ma3nesium sulphate, and the solvent is
removed in vacuo. The crude product, in 370 ml of boiling
hexane, is stirrcd for 3 to 4 hours, the mixture is then
cooled for 15 hours at bet~een 0C and 5C and is
filtered cold, and the f;lter residue is dried in vacuo at
50C for 2 to 3 hours.
146 9 ~71.2X of theory) of 2,3,6-tr;chloro-4-tr;-
fluoromethyl-phenylhydrazine, of nelting point 67 to 70C,
are obtained, the material be;ng 96X pure as determined by
gas chromatography.
Example 3
0 _ CL
F~C-S~NH-NH2
O C~
85 ~ tO.27 mole) of 1,2,3-trichloro-5-trifluoro-
methylsulphonylbenzene in 68 ml of dioxane are added drop~ise to
41 9 (0.82 mole) of hydraz;ne hydrate in 136 ml of d;oxane
at bet~een 20C and 40C, u;th stirring. After comple-
tion of the addition, the mixture is stirred under reflux
for 2 hours at 100-105C. ~hen the reaction mixture has
cooled, water is added and the resu~ting precipitate is
filtered off, dried and recrystallised from toluene.
68 9 ~81X of theory) of 2,6-dichloro-4-trifluoro-
methylsulphonyl-phenylhydrazine of melting point 135 to
137c, are obta;ned.
The follo~;ng substituted phenylhydraz;nes of the
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1249601
formula ~I) can be obtained analogously and in accordance
~ith the Qeneral ~tat-nents concernino the preparation
method:
Rt Cl
R3-(X)n ~ NH-NH2 ~I)
R2 Cl
5 Table 1
Exampl eR1 R2 X R3 n melting point / C
No I~L.~
4 H ~ S CF3 1 60 - 62
Cl Cl S c~3
6 Cl H S02 CF3
7 H H SO2 CC12P
B H H S02 CClF2
9 H ~ SO CF3
Preparation of the st~rtin9 co-Poun-d
O C~
~3C-S~=~CI
0 CL
A m;xture of 1,123 g ~4.6 molcs) of 4-trifluoro-
methylsulphonylchlorobenzene, 11.5 g ~0.13 mole) of iron-
~II) sulphide and 11.5 g ~0.045 mole) of iodine is treated
~ith chlorine at bet~een 100C and 120C. The reaction
is follo~ed by ~as chromatography and is stopped ~hen the
mixture contains 36% of the desired product. ~orking up
is by fractional d;stillation.
554 g ~38.5X of theory) of 3,4,5-tr;chlorotri-
fluoromethylsulphonylbenzene, of boiling point 143C at
22 mbar and melting point 102C to 103C, are obtained.
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Example of the proparati~n of ~ h~rbieidaLly ~ctive compound
,~
H~N ~ NH-C0-e2~5 ~VI-1)
tl ~ Cl
~f~
To a suspension of 3.5 9 ~0.01 mole) of 5-amino-4-
cyano-1-~2,6-dichloro-4-tr;fluoromethylthio-phenyl)-pyra-
S zole in 30 ml of chloroform there are added at 0C, ~ithstirrln~, f1rst tO ml 10.11 mole) of prop;onyl chlor;de
and thereafter 1.8 ml ~0.02 mole) of pyr;dine in 15 ml of
chloroform. A clear solut;on is obta;ned, ~hich after
completion of the addition is stirred for a further 20
hours at room temperature. The solution thus obtained is
evaporated to dryness. For ~orkin~ up, the residue is
taken up ;n S0 ml of ethanol, aqueous ammonia ;s added
until an alkaline reaction is obtained, the m;xture ;s
heated for 10 m;nutes under reflux, the volatile const;tu-
ents are removed ;n vacuo, the residue 1s taken up in100 ml of chloroform, the solution is ~ashed u;th ~ater,
then u;th 2N aqueous hydrochloric ac;d and aga;n with uater
and is dried over sodium sulphate, and the solvent is
removed in vacuo. 3.4 9 ~83X of theory) of 5-propionyl-
am;no-4-cyano-1-~2,6-d;chloro-4-trifluoromethylth;ophenyl)-
pyrazole, of me~ting point 153 to 156C, are obtained.
Preparatlon of the start;ng compounds
Cl
~C-S~ ~ -~H ~ c~ y t~ tN ~V-1)
Cl
6.1 9 (0.05 mole) of ~thoxymethylenenalonodinitrile
are added, ~ith stirring, to a suspension of 13.9 y (0.05
mole) of (2,6-dichloro-4-trifluoromethylthio)-pheny~hydra-
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zine and 2.1 ~ C0.025 mole) of sodium acetate in 25 nL of
g~acial acetic acid. ~fter compLetion of the addition,
stirring is continued for an hour at room temperature and
the solid thus obtained is filtered off, ~ashed succes-
siveLy ~ith ~ater, aqueous sodium bicarbonate solution andagain uith uater, and then dried. 15.8 ~ ~89X of theory)
of 1-~2,2-dicyanoethen-1-yl)-2-~2,6-dichloro-4-trifluoro-
~ethylthiophenyl)-hydrazine of meltlng point 160C are
obtained.
____", tN
Nb`~3-- N 112
Cl R~ Cl (lII-l)
SCF~
14.1 ~ ~0.04 nole) of 1-t2,2-dicyanoethen-1-yl)-2-
~2,6-dichloro-4-trifluoromethylth;o-phenyl)-hydrazine in
30 ml of ethylene glycol monoethyl ether are heated under
reflux for 2 hours. The hot solution is treated ~ith
active charcoal, filtered and diluted ~ith 60 ml of ~ater.
The precipltate uhich separates out is filtered off and
dried. 9.8 9 ~70Z of theory) of 5-amino-4-cyano-1-~2,6-
dichloro-4-trifluoronethylthiophenyl)-pyrazole, of melting
polnt 185 to 187C, are obtained.
Use ExanPle
In the use example ~hich follo~s, the compound
sho~n belo~ is employed as the comparison substance:
CN
~ .
N~N~ NH-tO-c2Hs
t~ ~ Cl (~)
4-Cyano-5-propionylam1no-1-(2,4,6-trichlorophenyl)-pyrazole
~kno~n from DE-OS ~6erman Published Specification) 3,226,513).
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Example A
Pre-emergence test
SoLvent: 5 parts by we;ght of acetone
Emuls;fier: 1 part by weight of aLkyLaryL poLygLycoL ether
To produce a suitabLe preparation of active com-
pound, 1 part by weight of active compound is mixed with
the stated amount of soLvent, the stated amount of emuL-
sifier is added and the concentrate is diluted with ~ater
to the desired concentration.
Seeds of the test plants are so~n in normal soil
and, after 24 hours, watered with the preparation of the
active compound. It is expedient to keep constant the
amount of water per unit area. The concentration of the
active compound in the preparation is of no importance,
onLy the amount of active compound appLied per unit area
being decisive. After three weeks, the degree of damage
to the plants is rated in X damage in comparison to the
development of the untreated control. The figures
denote:
OX = no action ~like untreated controL)
100X = total destruction
In this exampLe the compound according to Preparation
Example ~VI-I), for example, exhibits a distinct superiority
in herbicidal activity and in crop pLant seLectivity compared
to the prior art; this is particuLarLy true of wheat.
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