U.S. patent application number 09/748932 was filed with the patent office on 2001-08-02 for method for producing triazolinethione derivatives.
Invention is credited to Erdman, David, Jautelat, Manfred.
Application Number | 20010011138 09/748932 |
Document ID | / |
Family ID | 26040665 |
Filed Date | 2001-08-02 |
United States Patent
Application |
20010011138 |
Kind Code |
A1 |
Jautelat, Manfred ; et
al. |
August 2, 2001 |
Method for producing triazolinethione derivatives
Abstract
According to a novel process, triazolinethione derivatives of
the formula 1 in which R.sup.1 and R.sup.2 are each as defined in
the description, can be prepared by a) reacting hydrazine
derivatives of the formula 2 with formaldehyde and thiocyanate of
the formula X--SCN (III), in which X represents sodium, potassium
or ammonium, in the presence of a diluent and if appropriate in the
presence of an acid, and b) reacting the resulting
triazolidinethiones of the formula 3 either .alpha.) with oxidizing
agents, if appropriate in the presence of a catalyst and in the
presence of a diluent, or .beta.) with formic acid. The
triazolidinethiones of the formula (IV) are novel.
Inventors: |
Jautelat, Manfred;
(Burscheid, DE) ; Erdman, David; (Liberty,
MO) |
Correspondence
Address: |
BAYER CORPORATION
PATENT DEPARTMENT
100 BAYER ROAD
PITTSBURGH
PA
15205
US
|
Family ID: |
26040665 |
Appl. No.: |
09/748932 |
Filed: |
December 27, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09748932 |
Dec 27, 2000 |
|
|
|
09509763 |
Mar 28, 2000 |
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Current U.S.
Class: |
548/264.4 |
Current CPC
Class: |
C07D 249/12
20130101 |
Class at
Publication: |
548/264.4 |
International
Class: |
C07D 249/12 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 8, 1997 |
DE |
197 44 402.4 |
Sep 1, 1998 |
DE |
198 39 688.0 |
Claims
1. Process for preparing triazolinethione derivatives of the
formula 27in which R.sup.1 and R.sup.2 are identical or different
and each represents optionally substituted alkyl, optionally
substituted alkenyl, optionally substituted cycloalkyl, optionally
substituted aralkyl, optionally substituted aralkenyl, optionally
substituted aroxyalkyl, optionally substituted aryl or optionally
substituted heteroaryl, characterized in that a) in a first step
hydrazine derivatives of the formula 28in which R.sup.1 and R.sup.2
are each as defined above are reacted with formaldehyde and
thiocyanate of the formulaX--SCN (III), in which X represents
sodium, potassium or ammonium, in the presence of a diluent and if
appropriate in the presence of an acid, and b) the resulting
triazolidinethiones of the formula 29in which R.sup.1 and R.sup.2
are each as defined above are, in a second step, either .alpha.)
reacted with oxidizing agents, if appropriate in the presence of a
catalyst and in the presence of a diluent, or .beta.) reacted with
formic acid of the formulaHCOOH (V).
2. Process according to claim 1, characterized in that the starting
material used is
2-(1-chloro-cycloprop-1-yl)-3-(2-chloro-phenyl)-2-hydrox-
y-propyl-1-hydrazine of the formula 30
3. Process according to claim 1, characterized in that the
formaldehyde used for carrying out the first step is employed as
paraformaldehyde, as gaseous formaldehyde or as formalin
solution.
4. Process according to claim 1, characterized in that the reaction
component used for carrying out the first step is ammonium
thiocyanate.
5. Process according to claim 1, characterized in that the reaction
components used for carrying out the first step are sodium
thiocyanate in the presence of an acid.
6. Process according to claim 1, characterized in that the reaction
components used for carrying out the first step are sodium
thiocyanate in the presence of sodium hydrogen sulphate and
water.
7. Process according to claim 1, characterized in that the first
step is carried out at temperatures between -20.degree. C. and
+100.degree. C.
8. Process according to claim 1, characterized in that the second
step according to variant (.alpha.) is carried out at temperatures
between 0.degree. C. and 120.degree. C.
9. Process according to claim 1, characterized in that the second
step according to variant (.beta.) is carried out at temperatures
between 50.degree. C. and 100.degree. C.
10. Triazolidinethiones of the formula 31in which R.sup.1 and
R.sup.2 are identical or different and each represents optionally
substituted alkyl, optionally substituted alkenyl, optionally
substituted cycloalkyl, optionally substituted aralkyl, optionally
substituted aralkenyl, optionally substituted aroxyalkyl,
optionally substituted aryl or optionally substituted
heteroaryl.
11. Process for preparing triazolinethione derivatives of the
formula 32in which R.sup.1 and R.sup.2 are identical or different
and each represents optionally substituted alkyl, optionally
substituted alkenyl, optionally substituted cycloalkyl, optionally
substituted aralkyl, optionally substituted aralkenyl, optionally
substituted aroxyalkyl, optionally substituted aryl or optionally
substituted heteroaryl, characterized in that
1-chloro-2-hydroxy-ethane derivatives of the formula 33in which
R.sup.1 and R.sup.2 are each as defined above are reacted with
hydrazine hydrate, if appropriate in the presence of a diluent, the
resulting hydrazine derivatives of the formula 34in which R.sup.1
and R.sup.2 are each as defined above are reacted without prior
isolation with formaldehyde and thiocyanate of the formulaX--SCN
(III), in which X represents sodium, potassium or ammonium, in the
presence of a diluent and if appropriate in the presence of an
acid, and the resulting triazolidinethiones of the formula 35in
which R.sup.1 and R.sup.2 are each as defined above are either
.alpha.) reacted with oxidizing agents, if appropriate in the
presence of a catalyst and in the presence of a diluent, or .beta.)
are reacted with formic acid of the formulaHCOOH (V).
Description
[0001] The present invention relates to a novel process for
preparing triazolinethione derivatives which are known as active
compounds having microbicidal, in particular fungicidal,
properties.
[0002] It is already known that triazolinethione derivatives can be
prepared by either reacting the corresponding triazole derivatives
successively with strong bases and sulphur and then hydrolysing
them, or reacting them directly with sulphur at high temperatures,
followed by treatment with water (cf. WO-A 96-16 048). However,
this process has the disadvantage that the desired products are
obtained in only relatively low yields, or that reaction conditions
are required which are difficult to maintain on an industrial
scale.
[0003] Furthermore, it has already been described that certain
1,2,4-triazoline-5-thiones substituted in the 3 position can be
prepared by reacting
N-chlorothioformyl-N-(1-chloroalk-1-ene)-amines with
carbonylhydrazine derivatives (cf. DE-A 196 01 032, DE-A 196 01 189
and EP-A 0 784 053). However, the synthesis of corresponding
substances which do not have a substituent in the 3 position is not
mentioned.
[0004] Furthermore, Bull. Chem. Soc. Japan 46, 2215 (1973)
discloses that triazolinethiones substituted in the 3 position can
be synthesized by reacting phenylhydrazine with sodium thiocyanate
and ketones or aldehydes in the presence of hydrochloric acid and
treating the resulting triazolidinethiones substituted in the 3
position with oxidizing agents. This process has the disadvantages
that very long reaction times are required and that no
triazolinethiones which are unsubstituted in the 3 position can be
obtained in this manner.
[0005] Finally, it is also known that
2-(1-chloro-cycloprop-1-yl)-1-(2-chl-
oro-phenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol is obtained when
[1-(2-chloro-phenyl)-2-(1-chloro-cycloprop-1-yl)-2-hydroxy]-propyl-hydraz-
ine is reacted with formamidine acetate (cf. DE-A 40 30 039).
However, thiono derivatives of triazoles are not obtainable by this
method.
[0006] It has now been found that triazolinethione derivatives of
the formula 4
[0007] in which
[0008] R.sup.1 and R.sup.2 are identical or different and each
represents optionally substituted alkyl, optionally substituted
alkenyl, optionally substituted cycloalkyl, optionally substituted
aralkyl, optionally substituted aralkenyl, optionally substituted
aroxyalkyl, optionally substituted aryl or optionally substituted
heteroaryl,
[0009] can be prepared by
[0010] a) reacting, in a first step, hydrazine derivatives of the
formula 5
[0011] in which
[0012] R.sup.1 and R.sup.2 are each as defined above with
formaldehyde and thiocyanate of the formula
[0013] X--SCN (III),
[0014]
[0015] in which
[0016] X represents sodium, potassium or ammonium,
[0017] in the presence of a diluent and if appropriate in the
presence of an acid, and
[0018] b) reacting the resulting triazolidinethiones of the formula
6
[0019] in which
[0020] R.sup.1 and R.sup.2 are each as defined above in a second
step either
[0021] .alpha.) with oxidizing agents, if appropriate in the
presence of catalyst and in the presence of a diluent, or
[0022] .beta.) with formic acid of the formula
HCOOH (V)
[0023] It is extremely surprising that triazolinethione derivatives
of the formula (I) can be prepared by the process according to the
invention in substantially higher yields or under considerably
simpler conditions than by the prior-art methods.
[0024] The process according to the invention has a number of
advantages. Thus, as already mentioned, it makes it possible to
synthesize triazolinethiones of the formula (I) in high yield. It
is also favourable that the required starting materials and
reaction components can be prepared in a simple manner and are
available even in relatively large amounts. A further advantage
consists in the fact that the individual reaction steps can be
carried out and the reaction products can be isolated without any
problems.
[0025] Using
[1-(2-chloro-phenyl)-2-(1-chloro-cycloprop-1-yl)-2-hydroxy]-p-
ropyl-1-hydrazine as starting material and reacting this in the
first step with paraformaldehyde and ammonium thiocyanate and
allowing the resulting product to react in the second step with
oxygen in the presence of potassium hydroxide and sulphur, the
course of the process according to the invention can be illustrated
by the scheme below. 7
[0026] The formula (II) provides a general definition of the
hydrazine derivatives required as starting materials for carrying
out the process according to the invention. Preference is given to
using compounds of the formula (II) in which
[0027] R.sup.1 represents straight-chain or branched alkyl having 1
to 6 carbon atoms, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of halogen, alkoxy having 1 to 4 carbon atoms,
alkoximino having 1 to 4 carbon atoms in the alkoxy moiety and
cycloalkyl having 3 to 7 carbon atoms, or
[0028] represents straight-chain or branched alkenyl having 2 to 6
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkoxy having 1 to 4 carbon atoms and
cycloalkyl having 3 to 7 carbon atoms, or
[0029] represents cycloalkyl having 3 to 7 carbon atoms, where each
of these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of halogen, cyano
and alkyl having 1 to 4 carbon atoms, or
[0030] represents aralkyl having 6 to 10 carbon atoms in the aryl
moiety and 1 to 4 carbon atoms in the straight-chain or branched
alkyl moiety, where the aryl moiety may in each case be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkyl having 1 to 4 carbon atoms,
alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon
atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms, halogenoalkoxy having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical
or different halogen atoms, cycloalkyl having 3 to 7 carbon atoms,
phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the
alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atoms in the
alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitro
and cyano, or
[0031] represents aralkenyl having 6 to 10 carbon atoms in the aryl
moiety and 2 to 4 carbon atoms in the alkenyl moiety, where the
aryl moiety may in each case be mono- to trisubstituted by
identical or different substituents from the group consisting of
halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4
carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl
having 1 or 2 carbon atoms and 1 to 5 identical or different
halogen atoms, halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms, halogenoalkylthio having 1 or
2 carbon atoms and 1 to 5 identical or different halogen atoms,
cycloalkyl having 3 to 7 carbon atoms, phenyl, phenoxy,
alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,
alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and
1 to 4 carbon atoms in the alkyl moiety, nitro and cyano, or
[0032] represents aroxyalkyl having 6 to 10 carbon atoms in the
aryl moiety and 1 to 4 carbon atoms in the straight-chain or
branched oxyalkyl moiety, where the aryl moiety may in each case be
mono- to trisubstituted by identical or different substituents from
the group consisting of halogen, alkyl having 1 to 4 carbon atoms,
alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon
atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms, halogenoalkoxy having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical
or different halogen atoms, cycloalkyl having 3 to 7 carbon atoms,
phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the
alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atoms in the
alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitro
and cyano, or
[0033] represents aryl having 6 to 10 carbon atoms, where each of
these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of halogen, alkyl
having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms,
alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical or
different halogen atoms, halogenoalkylthio having 1 or 2 carbon
atoms and 1 to 5 identical or different halogen atoms, cycloalkyl
having 3 to 7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having
1 to 4 carbon atoms in the alkoxy moiety, alkoximinoalkyl having 1
to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in
the alkyl moiety, nitro and cyano, or
[0034] represents an optionally benzo-fused five- or six-membered
heteroaromatic radical having 1 to 3 heteroatoms, such as nitrogen,
sulphur and/or oxygen, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkyl having 1 to 4 carbon atoms,
hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkinyl having 3 to
8 carbon atoms, alkoxy having 1 or 2 carbon atoms, alkylthio having
1 or 2 carbon atoms, halogenoalkyl, halogenoalkoxy and
halogenoalkylthio having in each case 1 or 2 carbon atoms and 1 to
5 identical or different halogen atoms, such as fluorine or
chlorine atoms, formyl, dialkoxymethyl having 1 or 2 carbon atoms
in each alkoxy group, acyl having 2 to 4 carbon atoms,
alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,
alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and
1 to 3 carbon atoms in the alkyl moiety, nitro and cyano, and
[0035] R.sup.2 represents straight-chain or branched alkyl having 1
to 6 carbon atoms, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of halogen, alkoxy having 1 to 4 carbon atoms,
alkoximino having 1 to 4 carbon atoms in the alkoxy moiety and
cycloalkyl having 3 to 7 carbon atoms, or
[0036] represents straight-chain or branched alkyl having 2 to 6
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkoxy having 1 to 4 carbon atoms and
cycloalkyl having 3 to 7 carbon atoms, or
[0037] represents cycloalkyl having 3 to 7 carbon atoms, where each
of these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of halogen, cyano
and alkyl having 1 to 4 carbon atoms, or
[0038] represents aralkyl having 6 to 10 carbon atoms in the aryl
moiety and 1 to 4 carbon atoms in the straight-chain or branched
alkyl moiety, where the aryl moiety may in each case be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkyl having 1 to 4 carbon atoms,
alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon
atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms, halogenoalkoxy having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical
or different halogen atoms, cycloalkyl having 3 to 7 carbon atoms,
phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the
alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atoms in the
alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitro
and cyano, or
[0039] represents aralkenyl having 6 to 10 carbon atoms in the aryl
moiety and 2 to 4 carbon atoms in the alkenyl moiety, where the
aryl moiety may initially be mono- to trisubstituted by identical
or different substituents from the group consisting of halogen,
alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon
atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1
or 2 carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical or
different halogen atoms, halogenoalkylthio having 1 or 2 carbon
atoms and 1 to 5 identical or different halogen atoms, cycloalkyl
having 3 to 7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having
1 to 4 carbon atoms in the alkoxy moiety, alkoximinoalkyl having 1
to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in
the alkyl moiety, nitro and cyano, or
[0040] represents aroxyalkyl having 6 to 10 carbon atoms in the
aryl moiety and 1 to 4 carbon atoms in the straight-chain or
branched oxyalkyl moiety, where the aryl moiety may in each case be
mono- to trisubstituted by identical or different substituents from
the group consisting of halogen, alkyl having 1 to 4 carbon atoms,
alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon
atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5
identical or different halogen atoms, halogenoalkoxy having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical
or different halogen atoms, cycloalkyl having 3 to 7 carbon atoms,
phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the
alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atoms in the
alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitro
and cyano, or
[0041] represents aryl having 6 to 10 carbon atoms, where each of
these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of halogen, alkyl
having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms,
alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2
carbon atoms and 1 to 5 identical or different halogen atoms,
halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical or
different halogen atoms, halogenoalkylthio having 1 or 2 carbon
atoms and 1 to 5 identical or different halogen atoms, cycloalkyl
having 3 to 7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having
1 to 4 carbon atoms in the alkoxy moiety, alkoximinoalkyl having 1
to 4 carbon atoms in the alkoxy moiety and 1 to 4 carbon atoms in
the alkyl moiety, nitro and cyano, or
[0042] represents an optionally benzo-fused five- or six-membered
heteroaromatic radical having 1 to 3 heteroatoms, such as nitrogen,
sulphur and/or oxygen, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of halogen, alkyl having 1 to 4 carbon atoms,
hydroxyalkyl having 1 to 4 carbon atoms, hydroxyalkinyl having 3 to
8 carbon atoms, alkoxy having 1 or 2 carbon atoms, alkylthio having
1 or 2 carbon atoms, halogenoalkyl, halogenoalkoxy and
halogenoalkylthio having in each case 1 or 2 carbon atoms and 1 to
5 identical or different halogen atoms, such as fluorine or
chlorine atoms, formyl, dialkoxymethyl having 1 or 2 carbon atoms
in each alkoxy group, acyl having 2 to 4 carbon atoms,
alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,
alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and
1 to 3 carbon atoms in the alkyl moiety, nitro and cyano.
[0043] Particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0044] R.sup.1 represents straight-chain or branched alkyl having 1
to 4 carbon atoms, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, alkoximino having 1 or 2 carbon atoms in the
alkoxy moiety, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,
or
[0045] represents straight-chain or branched alkenyl having 2 to 5
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl, or
[0046] represents cycloalkyl having 3 to 6 carbon atoms, where each
of these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of fluorine,
chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl and
tert-butyl, or
[0047] represents phenylalkyl having 1 to 4 carbon atoms in the
straight-chain or branched alkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0048] represents phenylalkenyl having 2 to 4 carbon atoms in the
alkenyl moiety, where the phenyl moiety may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methyl, ethyl,
tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,
trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,
difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and
cyano, or
[0049] represents phenoxyalkyl having 1 to 4 carbon atoms in the
straight-chain or branched oxyalkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0050] represents phenyl which may be mono- to trisubstituted by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,
chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,
methoximinomethyl, 1-methoximinoethyl, nitro and cyano, or
[0051] represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl,
furanyl, thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl,
triazinyl, quinolinyl, isoquinolinyl, quinazolinyl, indolyl,
benzothienyl, benzofuiranyl, benzothiazolyl or benzimidazolyl,
where each of these radicals may be mono- to trisubstituted by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy,
chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl,
hydroxyalkinyl having 4 to 6 carbon atoms, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro,
cyano, formyl, dimethoxymethyl, acetyl and propionyl, and
[0052] R.sup.2 represents straight-chain or branched alkyl having 1
to 4 carbon atoms, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, alkoximino having 1 or 2 carbon atoms in the
alkoxy moiety, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,
or
[0053] represents straight-chain or branched alkenyl having 2 to 5
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl, or
[0054] represents cycloalkyl having 3 to 6 carbon atoms, where each
of these radicals may be mono- to trisubstituted by identical or
different substituents from the group consisting of fluorine,
chlorine, bromine, cyano, methyl, ethyl, propyl, isopropyl and
tert-butyl, or
[0055] represents phenylalkyl having 1 to 4 carbon atoms in the
straight-chain or branched alkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0056] represents phenylalkenyl having 2 to 4 carbon atoms in the
alkenyl moiety, where the phenyl moiety may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methyl, ethyl,
tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,
trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,
difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1 -methoximinoethyl, nitro and
cyano, or
[0057] represents phenoxyalkyl having 1 to 4 carbon atoms in the
straight-chain or branched oxyalkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0058] represents phenyl which may be mono- to trisubstitued by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,
chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,
methoximinomethyl, 1-methoximinoethyl, nitro and cyano, or
[0059] represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl,
furanyl, thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl,
triazinyl, quinolinyl, isoquinolinyl, quinazolinyl, indolyl,
benzothienyl, benzofuiranyl, benzothiazolyl or benzimidazolyl,
where each of these radicals may be mono- to trisubstituted by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy,
chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl,
hydroxyalkinyl having 4 to 6 carbon atoms, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro,
cyano, formyl, dimethoxymethyl, acetyl and propionyl.
[0060] Very particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0061] R.sup.1 represents n-propyl, isopropyl, n-butyl, i-butyl,
sec-butyl or tert-butyl, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, methoximino, ethoximino, cyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl, or
[0062] represents straight-chain or branched alkenyl having 2 to 5
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl, or
[0063] represents 1-methyl-cyclohexyl, cyclohexyl,
1-chloro-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl,
1-cyano-cyclopropyl, cyclopropyl, 1-methyl-cyclopentyl or
1-ethyl-cyclopentyl, or
[0064] represents phenylalkyl having 1 or 2 carbon atoms in the
straight-chain or branched alkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0065] represents phenylalkenyl having 2 to 4 carbon atoms in the
alkenyl moiety, where the phenyl moiety may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methyl, ethyl,
tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,
trifluoromethoxy, trifluoromethylthio, chlorodifluormethoxy,
difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and
cyano, or
[0066] represents phenoxyalkyl having 1 to 4 carbon atoms in the
straight-chain or branched oxyalkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluormethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0067] represents phenyl which may be mono- to trisubstituted by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,
chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,
methoximinomethyl, 1-methoximinoethyl, nitro and cyano, or
[0068] represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl,
furanyl, thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl,
triazinyl, quinolinyl, isoquinolinyl, quinazolinyl, indolyl,
benzothienyl, benzofuranyl, benzothiazolyl or benzimidazolyl, where
each of these radicals may be mono- to trisubstituted by identical
or different substituents from the group consisting of fluorine,
chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,
methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, chlorodifluoromethylthio, hydroxymethyl,
hydroxyethyl, hydroxyalkinyl having 4 to 6 carbon atoms,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro, cyano, formyl, dimethoxymethyl, acetyl
and propionyl, and
[0069] R.sup.2 represents n-propyl, isopropyl, n-butyl, i-butyl,
sec-butyl or tert-butyl, where these radicals may be mono- to
tetrasubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, methoximino, ethoximino, cyclopropyl,
cyclobutyl, cyclopentyl and cyclohexyl, or
[0070] represents straight-chain or branched alkenyl having 2 to 5
carbon atoms, where each of these radicals may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methoxy, ethoxy,
propoxy, isopropoxy, cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl, or
[0071] represents 1-methyl-cyclohexyl, cyclohexyl,
1-chloro-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl,
1-cyano-cyclopropyl, cyclopropyl, 1-methyl-cyclopentyl or
1-ethyl-cyclopentyl, or
[0072] represents phenylalkyl having 1 or 2 carbon atoms in the
straight-chain or branched alkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluormethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0073] represents phenylalkenyl having 2 to 4 carbon atoms in the
alkenyl moiety, where the phenyl moiety may be mono- to
trisubstituted by identical or different substituents from the
group consisting of fluorine, chlorine, bromine, methyl, ethyl,
tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,
trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,
difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,
ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and
cyano, or
[0074] represents phenoxyalkyl having 1 to 4 carbon atoms in the
straight-chain or branched oxyalkyl moiety, where the phenyl moiety
may be mono- to trisubstituted by identical or different
substituents from the group consisting of fluorine, chlorine,
bromine methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,
trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano, or
[0075] represents phenyl which may be mono- to trisubstituted by
identical or different substituents from the group consisting of
fluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy,
ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,
trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,
chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,
methoximinomethyl, 1-methoximinoethyl, nitro and cyano, or
[0076] represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl,
furanyl, thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl,
triazinyl, quinolinyl, isoquinolinyl, quinazolinyl, indolyl,
benzothienyl, benzofuranyl, benzothiazolyl or benzimidazolyl, where
each of these radicals may be mono- to trisubstituted by identical
or different substituents from the group consisting of fluorine,
chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,
methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,
chlorodifluoromethoxy, chlorodifluoromethylthio, hydroxymethyl,
hydroxyethyl, hydroxyalkinyl having 4 to 6 carbon atoms,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro, cyano, formyl, dimethoxymethyl, acetyl
and/ propionyl.
[0077] The hydrazine derivatives of the formula (II) are known or
can be prepared by processes known in principle (cf. DE-A-40 30
039).
[0078] Thus, hydrazine derivatives of the formula (II) are obtained
by reacting 1-chloro-2-hydroxyethane derivatives of the formula
8
[0079] in which
[0080] R.sup.1 and R.sup.2 are each as defined above,
[0081] in the presence of an acid binder, such as potassium
tert-butoxide, sodium methoxide or potassium carbonate, and in the
presence of a diluent, such as dimethylformamide, methanol,
n-butanol, tetrahydrofuran or methyl tert-butyl ether, at
temperatures between 20.degree. C. and 60.degree. C., and reacting
the resulting oxirane derivatives of the formula 9
[0082] in which
[0083] R.sup.1 and R.sup.2 are each as defined above
[0084] with hydrazine hydrate, if appropriate in the presence of a
diluent, such as methanol, n-butanol, tetrahydrofuran, methyl
tert-butyl ether, dioxane or nitrites, such as acetonitrile, at
temperatures between 30.degree. C. and 120.degree. C.
[0085] Particular preference is given to reacting the
1-chloro-2-hydroxy-ethane derivatives of the formula (VI) with
excess hydrazine hydrate, acting here both as reactant and as base
and diluent.
[0086] The 1-chloro-2-hydroxy-ethane derivatives of the formula
(VI) are known or can be prepared by processes known in principle
(cf. DE-A 40 30 039 and EP-A 0 297 345).
[0087] The formaldehyde required as reaction component for carrying
out the first step of the process according to the invention can be
employed as paraformaldehyde, as gaseous formaldehyde or else as
formalin solution (=aqueous formaldehyde solution).
[0088] Furthermore, thiocyanates of the formula (III) are employed
as reaction components when carrying out the first step of the
process according to the invention. The thiocyanates of the formula
(III) are known.
[0089] Suitable diluents for carrying out the first step of the
process according to the invention are all inert organic solvents
which are customary for such reactions. Preference is given to
using alcohols, such as n-butanol and tert-butanol, furthermore
ethers such as dioxane and methyl tert-butyl ether, moreover
nitrites, such as acetonitrile, and hydrocarbons, such as toluene
or chlorobenzene, in each case if appropriate as a mixture with
water.
[0090] Suitable acids for carrying out the first step of the
process according to the invention are all customary inorganic and
organic acids. Preference is given to using hydrochloric acid,
sulphuric acid, p-toluenesulphonic acid and also sodium hydrogen
sulphate in the presence of water.
[0091] Both the first and the second step of the process according
to the invention are generally carried out under atmospheric
pressure. However, it is also possible to operate under elevated
pressure or, if no gaseous components participate in the reaction,
under reduced pressure.
[0092] When carrying out the first step of the process according to
the invention, generally from 1 to 2 mol of formaldehyde and from 1
to 2 mol of thiocyanate of the formula (III) and, if appropriate,
an equivalent amount of acid or sodium hydrogen sulphate and water,
where the water may also be present in excess, are employed per
mole of hydrazine derivative of the formula (II). Work-up is
carried out by customary methods. If the reaction is carried out in
the absence of water, the reaction mixture is, if appropriate after
prior dilution with an organic solvent which is sparingly
water-miscible, generally washed with aqueous-alkaline solution,
and the organic phase is dried and concentrated. If the reaction is
carried out in the presence of water and in the presence of sodium
hydrogen sulphate, the reaction mixture is generally diluted with
an organic solvent which is sparingly water-miscible, filtered and
concentrated under reduced pressure. Any impurities which may then
still be present can be removed by customary methods, such as
recrystallization or chromatography.
[0093] The formula (IV) provides a general definition of the
triazolidinethiones required as starting materials for carrying out
the second step of the process according to the invention. In this
formula, R.sup.1 and R.sup.2 preferably have those meanings which
have already been mentioned in connection with the description of
the hydrazine derivatives of the formula (II) as being preferred
for these radicals.
[0094] The triazolidinethiones of the formula (IV) have hitherto
not been disclosed. They can be prepared by the reaction of the
first step of the process according to the invention.
[0095] Preferred oxidizing agents for carrying out the second step
of the process according to the invention according to variant (a)
are oxygen, sulphur and potassium peroxide. If the oxidizing agent
used is oxygen, this is preferably added in the form of air.
[0096] Preferred catalyst for carrying out the second step of the
process according to the invention according to variant (.alpha.)
is a mixture of potassium hydroxide and sulphur powder. This
catalyst is preferably employed when the oxidizing agent used is
oxygen.
[0097] Suitable diluents for carrying out the second step of the
process according to the invention according to variant (.alpha.)
are all inert organic solvents which are customary for such
reactions. Preference is given to using aliphatic, cycloaliphatic
and aromatic hydrocarbons, such as pentane, hexane, cyclohexane,
benzene, toluene and xylene, furthermore ethers, such as methyl
tert-butyl ether, and also esters, such as n-butyl acetate.
[0098] When carrying out the second step of the process according
to the invention according to variant (.alpha.), the reaction
temperatures can be varied within a relatively wide range. In
general, the reaction is carried out at temperatures between
0.degree. C. and 120.degree. C. If the oxidizing agent used is
oxygen, the reaction is preferably carried out at temperatures
between 20.degree. C. and 80.degree. C. If the oxidizing agent used
is sulphur, the reaction is preferably carried out at temperatures
between 50.degree. C. and 110.degree. C. If the oxidizing agent
used is potassium peroxide, the reaction is preferably carried out
at temperatures between 20.degree. C. and 80.degree. C.
[0099] When carrying out the second step of the process according
to the invention according to variant (.alpha.), in general an
excess of oxidizing agent is used per mole of triazolidinethione of
the formula (IV). If the oxidizing agent used is sulphur or
potassium peroxide, preference is given to using from 1.5 to 2 mol
of oxidizing agent per mole of triazolidinethione of the formula
(IV). If the oxidizing agent used is oxygen in the form of air,
preference is given to passing a stream of air through the reaction
mixture until the reaction has ended. Work-up is in each case
carried out by customary methods. In general, the reaction mixture
is, if appropriate after prior dilution with an organic solvent
which is sparingly water-miscible, extracted with aqueous salt
solution, and the organic phase is dried and concentrated. Any
impurities which may then still be present can be removed by
customary methods, such as recrystallization or chromatography.
However, it is also possible to isolate the product as the
potassium salt and then to liberate the product by addition of
acid.
[0100] When carrying out the second step of the process according
to the invention according to variant (.beta.), the reaction
temperatures can likewise be varied within a certain range. In
general, the reaction is carried out at temperatures between
50.degree. C. and
[0101] When carrying out the second step of the process according
to the invention according to variant (.beta.), formic acid acts
both as reaction component and as diluent. Thus, in general a high
excess of formic acid is employed per mole of triazolidinethione of
the formula (IV). Once more, work-up is carried out by customary
methods. In general, the reaction mixture is concentrated under
reduced pressure and the desired product is isolated from the
residue that remains by recrystallization and/or by chromatographic
means.
[0102] In a particular variant, the process according to the
invention can be carried out such that 1-chloro-2-hydroxy-ethane
derivatives of the formula (VI) are reacted with hydrazine hydrate
and the resulting hydrazine derivatives of the formula (II) are
then reacted further without prior isolation. Thus,
triazolinethiones of the formula (I) can also be prepared by
[0103] reacting 1-chloro-2-hydroxy-ethane derivatives of the
formula 10
[0104] in which
[0105] R.sup.1 and R.sup.2 are each as defined above
[0106] with hydrazine hydrate, if appropriate in the presence of a
diluent,
[0107] reacting the resulting hydrazine derivatives of the formula
11
[0108] in which
[0109] R.sup.1 and R.sup.2 are each as defined above
[0110] without prior isolation with formaldehyde and thiocyanate of
the formula
X--SCN (III),
[0111] in which
[0112] X represents sodium, potassium or ammonium,
[0113] in the presence of a diluent and if appropriate in the
presence of an acid, and reacting the resulting triazolidinethiones
of the formula 12
[0114] in which
[0115] R.sup.1 and R.sup.2 are each as defined above either
[0116] .alpha.) with oxidizing agents, if appropriate in the
presence of a catalyst and in the presence of a diluent, or
[0117] .beta.) with formic acid of the formula
HCOOH (V).
[0118] Suitable diluents for carrying out the first step of this
variant of the process according to the invention are all customary
inert organic solvents. Preference is given to using alcohols, such
as n-butanol, and ethers, such as dioxane or methyl tert-butyl
ether, and also nitrites, such as acetonitrile. However, it is also
possible to carry out the reaction without additional solvent. In
this case, hydrazine hydrate is employed in excess, so that it acts
both as reaction component and as diluent.
[0119] When carrying out the first step of this variant of the
process according to the invention, the reaction temperatures can
be varied within a certain range. In general, the reaction is
carried out at temperatures between 60.degree. C. and 120.degree.
C., preferably between 70.degree. C. and 100.degree. C.
[0120] The first step of this variant of the process according to
the invention is preferably carried out such that between 3 and 20
mol, particularly preferably between 4 and 15 mol, of hydrazine
hydrate are employed per mole of 1-chloro-2-hydroxy-ethane
derivative of the formula (VI), and the mixture is then diluted
with an organic solvent which is sparingly water-miscible, such as
methyl tert-butyl ether, the aqueous phase is separated off, and
the organic phase is washed and dried and then used for the
subsequent reactions without any further work-up.
[0121] The other steps of this variant of the process according to
the invention are carried out in the manner described above.
[0122] The triazolinethione derivatives preparable according to the
invention can be present in the "thiono" form of the formula 13
[0123] or in the tautomeric "mercapto" form of the formula 14
[0124] For the sake of simplicity, only the "thiono" form is shown
in each case.
[0125] The triazolinethione derivatives preparable according to the
invention are known as active compounds having microbicidal, in
particular fungicidal, properties (cf. WO A 96-16048).
[0126] The practice of the process according to the invention is
illustrated by the examples below.
PREPARATION EXAMPLES
Example 1
[0127] 15
[0128] a) Preparation of the Compound of the Formula 16
[0129] With stirring, a mixture of 5.48 g (20 mmol) of
[2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxy]-propyl-1-hydra-
zine, 40 ml of methyl tert-butyl ether, 0.9 g (30 mmol) of
paraformaldehyde and 1.84 g (24 mmol) of ammonium thiocyanate is
heated at 60.degree. C. for 3 hours. After cooling to room
temperature, the reaction mixture is diluted with methyl tert-butyl
ether and washed with saturated aqueous sodium carbonate solution.
The organic phase is dried over sodium sulphate, filtered and
concentrated under reduced pressure. This gives 6.1 g of a product
which, according to HPLC analysis, comprises 86.9% of
2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydro-
xy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane. After addition of
a little dichioromethane,
2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-2-
-hydroxy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane precipitates
out in the form of a crystalline solid.
[0130] Melting point: 152-154.degree. C.
[0131] .sup.1H NMR spectrum (CDCl.sub.3, TMS, 250 MHz):
.delta.=0.8-1.3 (m,3H); 3.1 (d, J=14 Hz, 1H); 3.65 (d, J=14 Hz,
1H); 4.2 (s,2H); 4.45-4.65 (m,3H); 5.1 (t, NH); 7.15-7.6 (m,4H)
ppm
[0132] b) Preparation of the Compound of the Formula 17
[0133] With stirring, a stream of air is passed for 3.5 hours over
a mixture of 1.72 g (5 mmol) of 2-(1-chloro-cycloprop-
1-yl)-1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thiono-1-yl)--
propane, 10 ml of absolute toluene, 0.34 g (6 mmol1) of potassium
hydroxide powder and 10 mg of sulphur powder which had been heated
to 70.degree. C. The progress of the reaction is monitored by HPLC
analysis. After cooling to room temperature, the reaction mixture
is diluted with methyl tert-butyl ether and washed repeatedly with
saturated aqueous ammonium chloride solution. The organic phase is
dried over sodium sulphate, filtered and concentrated under reduced
pressure. This gives 2.2 g of a product which, according to HPLC
analysis, comprises 71% of
2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-tria-
zole-5-thiono-1-yl)-propan-2-ol. After recrystallization from
toluene, the substance has a melting point of from 136 to
138.degree. C.
Example 2
[0134] 18
[0135] a) Preparation of the Compound of the Formula 19
[0136] With stirring, a mixture of 2.78 g (10 mmol) of
3-chloro-2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-propan-2-ol
and 4.9 ml (100 mmol) of hydrazine hydrate is heated at 80.degree.
C. for 3 hours. The reaction mixture is then cooled to 20.degree.
C., 15 ml of methyl tert-butyl ether are added and the aqueous
phase is separated off. The organic phase is washed once with 5 ml
of water and then dried over 1 g of sodium sulphate. The reaction
mixture is then filtered, admixed with 0.3 g (10 mmol) of
paraformaldehyde and 0.76 g (20 mmol) of ammonium thiocyanate and
heated with stirring at from 55 to 60.degree. C. for 3 hours. The
mixture is allowed to cool to room temperature, admixed with methyl
tert-butyl ether and washed three times with saturated aqueous
ammonium chloride solution. The organic phase is dried over sodium
sulphate, filtered and concentrated under reduced pressure. This
gives 2.4 g of a product which, according to HPLC analysis,
comprises 68.3% of 2-(I-chloro-
cycloprop-1-yl)-1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triaz-
olidine-5-thiono-1-yl)-propane. After addition of a little
dichloromethane,
2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-2-hydrox-
y-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane precipitates out in
the form of a crystalline solid.
[0137] Melting point: 152-154.degree. C.
[0138] b) Preparation of the Compound of the Formula 20
[0139] With stirring, a mixture of 1.71 g (5 mmol) of 2-(1
-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triazolidi-
ne-5 -thiono-1-yl)-propane, 12.5 ml of n-butyl acetate and 0.25 g
(7.5 mmol) of sulphur powder is heated at 100.degree. C. for 9
hours, during which the progress of the reaction is monitored by
HPLC analysis. The reaction mixture is then cooled to room
temperature, diluted with methyl tert-butyl ether and washed
repeatedly with saturated aqueous ammonium chloride solution. The
organic phase is dried over sodium sulphate, filtered and
concentrated under reduced pressure. This gives 2.5 g of a product
which, according to HPLC analysis, comprises 72.2% of
2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-tria-
zole-5-thiono-1-yl)-propan-2-ol. After recrystallization from
toluene, the substance has a melting point of from 137 to
138.degree. C.
Example 3
[0140] 21
[0141] Under an atmosphere of nitrogen and with stirring, a mixture
of 27.8 g (0.1 mol) of
3-chloro-2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phen-
yl)-propan-2-ol and 48.5 ml (1 mol) of hydrazine hydrate is heated
at 100.degree. C. for 5 hours. After cooling of the two-phase
system to room temperature, the hydrazine phase is decanted off and
the residue is washed once with 20 ml of water. This gives 25.9 g
of a product which, according to gaschromatographic analysis,
comprises 86.8% of
2-(1-chloro-cycloprop-1-yl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydraz-
ine. Accordingly, the calculated yield is 94.5% of theory.
Recrystallization of the crude product from acetonitrile gives
2-(1-chloro-cycloprop-1-yl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydraz-
ine in the form of a solid of melting point 86.degree. C. to
88.degree. C.
[0142] .sup.1H NMR spectrum (400 MHz, CDCl.sub.3, TMS):
.delta.=0.8-1.05 (m,3H); 1.25 (m,1H); 2.7 (d,1H); 2.95 (d,1H); 3.45
(d,1H); 3.6 (d,1H); 2.8-3.5 (3H,NH); 4.6 (1H,OH); 7.1-7.5 (m,4H)
ppm
Example 4
[0143] 22
[0144] At 0.degree. C. and under an atmosphere of nitrogen, a
mixture of 2.74 g (10 mmol) of [2-(1
-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hy-
droxy]-propyl-1-hydrazine (which had been recrystallized from
acetonitrile), 10 ml of toluene and 0.5 ml of water is initially
charged. With stirring at 0.degree. C., formaldehyde, obtained by
prior depolymerization of 0.36 g (12 mmol) of paraformaldehyde at
about 150.degree. C., is passed in gaseous form together with a
stream of nitrogen into this mixture. After the addition has ended,
stirring is continued at 20.degree. C. for 30 minutes, and the
mixture is then admixed with 0.82 g (10 mmol) of sodium thiocyanate
and 1.2 g (10 mmol) of sodium hydrogen sulphate. The resulting
reaction mixture is stirred at 20.degree. C. for 2 hours and
subsequently diluted with 100 ml of dichloromethane. The solid is
filtered off and the liquid organic phase is concentrated under
reduced pressure. This gives 3.28 g of a product which, according
to HPLC analysis, comprises 98.6% of 2-(1-chloro-cycloprop-1-yl)-
1-(2-chloro-phenyl)-2-hydroxy-3-(1,2,4-triaz-
olidine-5-thiono-1-yl)-propane. Accordingly, the calculated yield
is 95% of theory.
[0145] Melting point: 157-158.degree. C.
Example 5
[0146] 23
[0147] At 0.degree. C. and under an atmosphere of nitrogen, a
mixture of 2.74 g (10 mmol) of
[2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hyd-
roxy]-propyl-1-hydrazine (which had been recrystallized from
acetonitrile) and 10 ml of toluene is admixed with stirring with
0.74 ml (10 mmol) of a 40% strength formalin solution. After the
addition has ended, the mixture is stirred at 20.degree. C. for 30
minutes and then admixed with 0.82 g (10 mmol) of sodium
thiocyanate and 1.2 g (10 mmol) of sodium hydrogen sulphate. The
reaction mixture is stirred at 20.degree. C. for 2 hours and
subsequently diluted with 100 ml of dichloromethane. The solid is
filtered off and the liquid organic phase is concentrated under
reduced pressure. This gives 3.3 g of a product which, according to
HPLC analysis, comprises 93.9% of
2-(1-chloro-cycloprop-1-yl)-1-(2-chloropheny-
l)-2-hydroxy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane.
Accordingly, the calculated yield is 90.2% of theory.
[0148] Melting point: 154-155.degree. C.
Example 6
[0149] 24
[0150] At 0.degree. C. and under an atmosphere of nitrogen, a
mixture of 2.74 g (10 mmol) of
[2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hyx-
roxy]-propyl-1-hydrazine (which had been recrystallized from
acetonitrile) and 10 ml of toluene is successively admixed with
stirring with 1.2 g (10 mmol) of sodium hydrogen sulphate, 0.74 ml
(10 mmol) of a 40% strength formalin solution and 0.82 g (10 mmol)
of sodium thiocyanate. After the addition has ended, the mixture is
stirred at 20.degree. C. for 2 hours and then diluted with 100 ml
of dichloromethane. The solid is filtered off and the liquid
organic phase is concentrated under reduced pressure. This gives
3.4 g of a product which, according to HPLC analysis, comprises
83.1% of 2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydro-
xy-3-(1,2,4-triazolidine-5-thiono-1-yl)-propane. Accordingly, the
calculated yield is 83% of theory.
[0151] Melting point: 136-138.degree. C.
COMPARATIVE EXAMPLES
Example A
[0152] 25
[0153] At -20.degree. C., a mixture of 3.12 g (10 mmol) of
2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-pro-
pan-2-ol and 45 ml of absolute tetrahydrofuran is admixed with 8.4
ml (21 mmol) of n-butyl-lithium in hexane and stirred at 0.degree.
C. for 30 minutes. The reaction mixture is then cooled to
-70.degree. C., admixed with 0.32 g of (10 mmol) of sulphur powder
and stirred at -70.degree. C. for 30 minutes. The mixture is warmed
to -10.degree. C., admixed with ice-water and adjusted to pH 5 by
addition of dilute sulphuric acid. The mixture is extracted
repeatedly with ethyl acetate, and the combined organic phases are
dried over sodium sulphate and concentrated under reduced pressure.
In this manner, 3.2 g of a product which, according to
gaschromatographic analysis, comprises 95% of
2-(1-chloro-cycloprop-1-yl)-
-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazole-5-thiono-1-yl)-propan-3-
-ol are obtained. After recrystallization from toluene, the
substance has a melting point of from 138.degree. C. to 139.degree.
C.
Example B
[0154] 26
[0155] With stirring, a mixture of 3.12 g (10 mmol) of
2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(1,2,4-triazol-1-yl)-pr-
opan-2-ol, 0.96 g (30 mmol) of sulphur powder and 20 ml of absolute
N-methyl-pyrrolidone is heated at 200.degree. C. for 44 hours. The
reaction mixture is then concentrated under reduced pressure (0.2
mbar). The resulting crude product (3.1 g) is recrystallized from
toluene. In this manner, 0.7 g (20% of theory) of
2-(1-chloro-cycloprop-1-yl)-1-(2-ch-
loro-phenyl)-3-(4,5-dihydro-1,2,4-triazole-5-thiono-1-yl)-propan-2-ol
is obtained in the form of a solid which melts at 138-139.degree.
C.
* * * * *