U.S. patent application number 09/795062 was filed with the patent office on 2002-02-28 for method for producing triazolinthion derivatives.
Invention is credited to Hupperts, Achim, Jautelat, Manfred, Lantzsch, Reinhard.
Application Number | 20020026058 09/795062 |
Document ID | / |
Family ID | 27614367 |
Filed Date | 2002-02-28 |
United States Patent
Application |
20020026058 |
Kind Code |
A1 |
Jautelat, Manfred ; et
al. |
February 28, 2002 |
Method for producing triazolinthion derivatives
Abstract
According to a novel process, it is possible to prepare
triazolinethione derivatives of the formula 1 in which R.sup.1 and
R.sup.2 are each as defined in the description by a) reacting
hydrazine derivatives of the formula 2 or their acid addition salts
with an inorganic or organic acid with thiocyanate of the formula 3
in which Y represents sodium, potassium or ammonium in the presence
of a diluent and, if appropriate, in the presence of a catalyst and
b) reacting the resulting thiosemicarbazide derivatives of the
formula 4 with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent. The
thiosemicarbazide derivatives of the formula (IV) are novel.
Inventors: |
Jautelat, Manfred;
(Burscheid, DE) ; Hupperts, Achim; (Dusseldorf,
DE) ; Lantzsch, Reinhard; (Wuppertal, DE) |
Correspondence
Address: |
BAYER CORPORATION
PATENT DEPARTMENT
100 BAYER ROAD
PITTSBURGH
PA
15205
US
|
Family ID: |
27614367 |
Appl. No.: |
09/795062 |
Filed: |
February 26, 2001 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
09795062 |
Feb 26, 2001 |
|
|
|
09509927 |
Apr 3, 2000 |
|
|
|
6262276 |
|
|
|
|
09509927 |
Apr 3, 2000 |
|
|
|
PCT/EP98/06113 |
Sep 25, 1998 |
|
|
|
Current U.S.
Class: |
548/263.2 |
Current CPC
Class: |
C07D 249/12 20130101;
C07C 337/06 20130101 |
Class at
Publication: |
548/263.2 |
International
Class: |
C07D 249/08 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 8, 1997 |
DE |
197 44 400.8 |
Claims
1. Process for preparing triazolinethione derivatives of the
formula (I) 23in 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 24in which R.sup.1
and R.sup.2 are each as defined above, or their addition salts with
an inorganic or organic acid, are reacted with thiocyanate of the
formula 25in which Y represents sodium, potassium or ammonium, in
the presence of a diluent and, if appropriate, in the presence of a
catalyst, and b) the resulting thiosemicarbazide derivatives of the
formula 26in which R.sup.1 and R.sup.2 are each as defined above
are reacted with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent.
2. Process according to claim 1, characterized in that the starting
material used is
2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-p-
ropyl-1-hydrazinium sulphate of the formula 27
3. Process according to claim 1, characterized in that the reaction
component used for carrying out the first step is ammonium
thiocyanate.
4. Process according to claim 1, characterized in that the first
step is carried out at temperatures between 50.degree. C. and
120.degree. C.
5. Process according to claim 1, characterized in that the second
step is carried out at temperatures between 80.degree. C. and
120.degree. C.
6. Thiosemicarbazide derivatives of the formula 28in 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.
7. Process for preparing triazolinethione derivatives of the
formula 29in 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 30in 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, and
the resulting hydrazine derivatives of the formula 31in which
R.sup.1 and R.sup.2 are each as defined above are, if appropriate,
reacted(with an inorganic or organic acid in the presence of a
diluent, and the hydrazine derivatives of the formula (II) or their
acid addition salts are reacted(without prior isolation with
thiocyanate of the formula 32in which Y represents sodium,
potassium or ammonium in the presence of a diluent and, if
appropriate, in the presence of a catalyst, and the resulting
thiosemicarbazide derivatives of the formula 33in which R.sup.1 and
R.sup.2 are each as defined above are reacted with formic acid, if
appropriate in the presence of a catalyst and if appropriate in the
presence of a diluent.
8. Thiosemicarbazide derivatives according to claim 6,
characterized by the formula 34
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 triazolidenethiones 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-cyclopropyl)-1-(2-chloro-
-phenyl)-3-(1,2,4-triazol-1yl)-propan-2-ole is obtained when
[1-(2-chloro-phenyl)-2-(1-chloro-cyclopropyl)-2-hydroxy]-propyl-1-hydrazi-
ne 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 5
[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 6
[0011] in which
[0012] R.sup.1 and R.sup.2 are each as defined above,
[0013] or their addition salts with an inorganic or organic
acid,
[0014] with thiocyanate of the formula 7
[0015] in which
[0016] Y represents sodium, potassium or ammonium,
[0017] in the presence of a diluent and, if appropriate, in the
presence of a catalyst, and
[0018] b) reacting the resulting thiosemicarbazide derivatives of
the formula 8
[0019] in which R.sup.1 and R.sup.2 are each as defined above
[0020] with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent.
[0021] It is extremely surprising that the triazolinethione
derivatives of the formula (I ) can be prepared by the process
according to the invention in substantially higher yields or under
considerably more simple conditions than by the prior-art methods.
It is likewise unexpected that, in the practice of the first step
of the process according to the invention, the attack of the
thiocyanate occurs predominantly not at the terminal but at the
substituted nitrogen atom of the hydrazine derivative of the
formula (II), thus yielding the desired isomer with high
selectivity.
[0022] The process according to the invention has a number of
advantages. Thus, as already mentioned, it is possible to
synthesize triazolinethione derivatives 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 steps can be carried out
and the reaction products can be isolated without any problems.
[0023] Using
2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-
-1-hydrazonium sulphate as starting material and reacting this in
the first step with ammonium thiocyanate and allowing the resulting
thiosemicarbazide to react in the second step with formic acid, the
course of the process according to the invention can be illustrated
by the scheme below. 9
[0024] 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
[0025] 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,
[0026] or
[0027] 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,
[0028] 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,
[0030] or
[0031] 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,
[0032] or
[0033] 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,
[0034] or
[0035] 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,
[0036] or
[0037] 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,
[0038] or
[0039] represents an optionally benzo-fused 5- or 6-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
[0040] 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,
[0041] or
[0042] 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,
[0043] or
[0044] 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,
[0045] or
[0046] represents aralkyl having 6 to 10 carbon atoms in the alkyl
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,
[0047] or
[0048] 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,
[0049] or
[0050] 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,
[0051] or
[0052] 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,
[0053] or
[0054] represents an optionally benzo-fused 5- or 6-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,
alkoximino-alkyl having 1 to 4 carbon atoms in the alkoxy moiety
and 1 to 3 carbon atoms in the alkyl moiety, nitro and cyano.
[0055] Particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0056] 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,
[0057] or
[0058] 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,
[0059] or
[0060] 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,
[0061] or
[0062] 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, chlorodifltioromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano,
[0063] or
[0064] 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,
[0065] 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, trifluoromethylthio,
chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,
methoxycarbonyl, ethoxycarbonyl, methoximinomethyl,
1-methoximinoethyl, nitro and cyano,
[0067] or
[0068] 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,
[0069] or
[0070] 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 and cyano, formyl, dimethoxymethyl,
acetyl and propionyl, and
[0071] 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/or
cyclohexyl,
[0072] or
[0073] 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,
[0074] or
[0075] 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,
[0076] or
[0077] 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,
[0078] or
[0079] 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,
[0080] or
[0081] 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,
[0082] or
[0083] 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,
[0084] or
[0085] 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 and cyano, formyl, dimethoxymethyl,
acetyl and propionyl.
[0086] Very particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0087] 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.
[0088] or
[0089] 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,
[0090] or
[0091] 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,
[0092] or
[0093] 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,
[0094] or
[0095] 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,
[0096] or
[0097] 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,
[0098] or
[0099] 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,
[0100] or
[0101] 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 and cyano, formyl, dimethoxymethyl,
acetyl and propionyl, and
[0102] 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,
[0103] or
[0104] 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,
[0105] or
[0106] 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,
[0107] or
[0108] 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,
[0109] or
[0110] 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,
[0111] or
[0112] 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,
[0113] or
[0114] 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,
[0115] or
[0116] 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 and cyano, formyl, dimethoxymethyl,
acetyl and propionyl.
[0117] Preference is also given to using addition salts of the
abovementioned preferred or particularly preferred hydrazine
derivatives of the formula (II) and an inorganic or organic acid.
Preference is given to hydrazonium salts of the formula 10
[0118] in which
[0119] R.sup.1 and R.sup.2 are each as defined above and
[0120] X.sup..crclbar. represents chloride or an equivalent of a
sulphate anion.
[0121] The hydrazine derivatives of the formula (II) are known or
can be prepared by processes known in principle (cf. DE-A 40 30
039).
[0122] Thus, hydrazine derivatives of the formula (II) are obtained
by reacting 1-chloro-2-hydroxy-ethane derivatives of the formula
11
[0123] in which
[0124] R.sup.1 and R.sup.2 are each as defined above
[0125] with hydrazine hydrate, if appropriate in the presence of a
diluent.
[0126] The hydrazine derivatives of the formula (II) can be
converted into their acid addition salts by reacting them with an
inorganic or organic acid in the presence of a diluent. The
1-chloro-2-hydroxy-ethane derivatives of the formula (V) are known
or can be prepared by processes known in principle (cf. DE-A 40 30
039 and EP-A 0 297 345).
[0127] Suitable diluents for the above process for preparing
hydrazine derivatives of the formula (II) are all customary inert
organic solvents. Preference is given to using alcohols, such as
methanol, ethanol or n-butanol, furthermore ethers, such as dioxane
or methyl tert-butyl ether, and also aromatic hydrocarbons, such as
benzene, toluene or xylene. However, it is also possible to carry
out the reaction without any additional solvent. In this case, an
excess of hydrazine hydrate is employed, so that it acts both as
reaction component and as diluent.
[0128] When carrying out the preparation of hydrazine derivatives
of the formula (II) according to the above process, the reaction
temperatures can be varied within a certain range. In general, the
process is carried out at temperatures between 60.degree. C. and
120.degree. C., preferably between 70.degree. C. and 110.degree.
C.
[0129] In the preparation of hydrazine derivatives of the formula
(II) according to the above process, in general from 1 to 20 mol,
preferably from 5 to 15 mol, of hydrazine hydrate are employed per
mole of 1-chloro-2-hydroxy-ethane derivative of the formula (V).
Work-up is carried out by customary methods. In general, the
reaction mixture is admixed with an organic solvent which is
sparingly water-miscible, such as methyl tert-butyl ether or
toluene, the aqueous phase is removed and the organic phase is
washed and dried.
[0130] Suitable diluents for converting the hydrazine derivatives
of the formula (II) into their acid addition salts are all organic
solvents which are customary for such reactions. Preference is
given to using aromatic hydrocarbons, such as benzene, toluene or
xylene, or ethers, such as dioxane or methyl tert-butyl ether.
[0131] The hydrazine derivatives of the formula (II) are generally
converted into salts at room temperature. However, it is also
possible to carry out the conversion at a slightly elevated or
reduced temperature.
[0132] The conversion of hydrazine derivatives of the formula (II)
into salts is generally carried out such that a hydrazine
derivative of the formula (II) is dissolved in a solvent and mixed
with an equivalent amount or an excess of acid. When preparing
chlorides, it is possible to use either hydrochloric acid or
gaseous hydrogen chloride. The salts can be isolated by customary
methods.
[0133] The thiocyanates of the formula (III) required as reaction
components for carrying out the first step of the process according
to the invention are known.
[0134] 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 aromatic hydrocarbons, such as benzene, toluene or xylene,
furthermore ethers, such as dioxane or methyl tert-butyl ether, and
also esters, such as ethyl acetate.
[0135] Suitable catalysts for carrying out the first step of the
process according to the invention are all reaction promoters which
are customary for such reactions. Preference is given to using
water.
[0136] When carrying out the first step of the process according to
the invention, the reaction temperatures can be varied within a
relatively wide range. In general, the reaction is carried out at
temperatures between 50.degree. C. and 120.degree. C., preferably
between 70.degree. C. and 110.degree. C.
[0137] 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 carry out the process
under elevated pressure or, if no gaseous components are involved
in the reaction, also under reduced pressure.
[0138] When carrying out the first step of the process according to
the invention, in general from 1 to 2 mol of thiocyanate of the
formula (III) and, if required, a small amount of catalyst are
employed per mole of hydrazine derivative of the formula (II).
Work-up is carried out by customary methods. In general, the
reaction mixture is washed with water, the organic phase is dried
and concentrated and the residue that remains is freed from
undesirable components by customary methods, for example by
chromatography or recrystallization.
[0139] The formula (IV) provides a general definition of the
thiosemicarbazide derivatives 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 each 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.
[0140] The thiosemicarbazide derivatives of the formula (IV) have
hitherto not been known. They can be prepared by the reaction of
the first step of the process according to the invention.
[0141] Suitable catalysts for carrying out the second step of the
process according to the invention are all reaction promoters which
are customary for such reactions. Preference is given to using
acids, such as hydrochloric acid or sulphuric acid, and furthermore
metal oxides, such as amorphous titanium dioxide.
[0142] Suitable diluents for carrying out the second step of the
process according to the invention are all weakly polar organic
solvents which are customary for such reactions. Preference is
given to using esters, such as ethyl acetate or isobutyl formate,
and also formic acid.
[0143] When carrying out the second step 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 80.degree. C. and 120.degree. C., preferably
between 90.degree. C. and 110.degree. C.
[0144] When carrying out the second step of the process according
to the invention, an excess, in general from 5 to 15 mol, of formic
acid and, if required, a small amount of catalyst are employed per
mole of thiosemicarbazide derivative of the of the formula (IV).
Work-up is carried out by customary methods. In general, the
reaction mixture is, if appropriate after prior dilution with an
organic solvent that is sparingly water-miscible, extracted with
aqueous salt solution, and the organic phase is dried and
concentrated. Any impurities which may still be present can then be
removed by customary methods, such as recrystallization or
chromatography.
[0145] 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 (V) are reacted with hydrazine hydrate
and the resulting hydrazine derivatives of the formula (II) are
then reacted further without prior isolation. Accordingly,
triazolinethiones of the formula (I) can also be prepared by
[0146] reacting 1-chloro-2-hydroxy-ethane derivatives of the
formula 12
[0147] in which
[0148] R.sup.1 and R.sup.2 are each as defined above
[0149] with hydrazine hydrate, if appropriate in the presence of a
diluent, and reacting the resulting hydrazine derivatives of the
formula 13
[0150] in which
[0151] R.sup.1 and R.sup.2 are each as defined above
[0152] if appropriate with an inorganic or organic acid in the
presence of a diluent,
[0153] and reacting the hydrazine derivatives of the formula (II)
or their acid addition salts
[0154] without prior isolation with thiocyanate of the formula
14
[0155] in which
[0156] Y represents sodium, potassium or ammonium
[0157] in the presence of a diluent and, if appropriate, in the
presence of a catalyst and
[0158] reacting the resulting thiosemicarbazide derivatives of the
formula 15
[0159] in which
[0160] R.sup.1 and R.sup.2 are each as defined above
[0161] with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent.
[0162] When carrying out the individual steps of this process, the
procedure which has already been described above is adopted.
[0163] The triazolinethione derivatives preparable according to the
invention can be present in the "thiono" form of the formula 16
[0164] or in the tautomeric "mercapto" form of the formula 17
[0165] For the sake of simplicity, only the "thiono" form is shown
in each case.
[0166] The triazolinethione derivatives preparable according to the
invention are known as active compounds with microbicidal, in
particular fungicidal, properties (cf. WO-A 96-16 048).
[0167] The practice of the process according to the invention is
illustrated by the examples below.
PREPARATION EXAMPLES
Example 1
[0168] 18
[0169] a) Preparation of the compound of the formula 19
[0170] With stirring, a mixture of 4.86 g (15 mmol) of
2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazini-
um sulphate, 1.26 g (16.5 mmol) of ammonium thiocyanate and 30 ml
of ethyl acetate is heated between 74 and 76.degree. C. for 3
hours. The reaction mixture is then allowed to cool to room
temperature and then washed with 20 ml of water. The organic phase
is dried over sodium sulphate, filtered and concentrated under
reduced pressure. This gives 5.81 g of a product which, according
to HPLC analysis, comprises 65.9% of the thiosemicarbazide
derivative of the formula (IV-1). Accordingly, the calculated yield
is 76.4% of theory. After recrystallization from methanol, the
thiosemicarbazide derivative of the formula (IV-1) is obtained in
the form of a crystalline solid which melts at from 128 to
129.degree. C.
[0171] b) Preparation of the compound of the formula 20
[0172] At room temperature, a mixture of 3.35 g (10 mmol) of
thiosemicarbazide derivative of the formula (IV-1) in 10 ml of
isobutyl formate is admixed with stirring with 5 ml (132 mmol) of
formic acid, and the mixture is then heated at 95.degree. C. for
5.5 hours. The reaction mixture is then cooled to room temperature
and subsequently diluted with 50 ml of ethyl acetate and washed
three times with 10 ml of saturated aqueous ammonium chloride
solution each time. The organic phase is dried over sodium
sulphate, filtered and concentrated under reduced pressure. This
gives 3.65 g of a product which, according to HPLC analysis,
comprises 86.4% of
2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-di-
hydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-ole. Accordingly, the
calculated yield is 91.6% of theory.
COMPARATIVE EXAMPLES
Example A
[0173] 21
[0174] At -20.degree. C., a mixture of 3.12 g (10 mmol) of
2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-
-2-ole 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 (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 gas chromatographic
analysis, comprises 95% of 2-(1-chloro-cyclopropyl)-1-
-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-ol-
e are obtained. Recrystallization from toluene gives this substance
as a solid which melts at from 138 to 139.degree. C.
Example B
[0175] 22
[0176] With stirring, a mixture of 3.12 g (10 mmol) of
2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(1,2,4-triazol-1-yl)-propa-
n-2-ole, 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-cyclopropyl)-1-(2-chlor-
o-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-ole
is obtained in the form of a solid which melts at from 138 to
139.degree. C.
* * * * *