U.S. patent application number 09/750589 was filed with the patent office on 2001-12-27 for method for producing triazolinethione derivatives.
Invention is credited to Erdman, David, Hupperts, Achim, Jautelat, Manfred, Lantzsch, Reinhard.
Application Number | 20010056187 09/750589 |
Document ID | / |
Family ID | 7844918 |
Filed Date | 2001-12-27 |
United States Patent
Application |
20010056187 |
Kind Code |
A1 |
Lantzsch, Reinhard ; et
al. |
December 27, 2001 |
Method for producing triazolinethione 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 with carbonyl compounds of
the formula 3 in which R.sup.3 and R.sup.4 are each as defined in
the description with potassium thiocyanate, sodium thiocyanate or
ammonium thiocyanate, if appropriate in the presence of a diluent
and if appropriate in the presence of an acid, and b) reacting the
resulting triazolidinethione 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 triazolidinethione
derivatives of the formula (V) are novel.
Inventors: |
Lantzsch, Reinhard;
(Wuppertal, DE) ; Jautelat, Manfred; (Burscheid,
DE) ; Hupperts, Achim; (Dusseldorf, DE) ;
Erdman, David; (Liberty, MO) |
Correspondence
Address: |
BAYER CORPORATION
PATENT DEPARTMENT
100 BAYER ROAD
PITTSBURGH
PA
15205
US
|
Family ID: |
7844918 |
Appl. No.: |
09/750589 |
Filed: |
December 28, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09750589 |
Dec 28, 2000 |
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09509889 |
Apr 3, 2000 |
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6271389 |
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09509889 |
Apr 3, 2000 |
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PCT/EP98/06111 |
Sep 25, 1998 |
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Current U.S.
Class: |
546/272.4 ;
548/263.2 |
Current CPC
Class: |
C07D 249/12
20130101 |
Class at
Publication: |
546/272.4 ;
548/263.2 |
International
Class: |
C07D 41/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 8, 1997 |
DE |
197 44 401.6 |
Claims
1. 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 a) in a first step,
hydrazine derivative of the formula 30in which R.sup.1 and R.sup.2
are each as defined above are reacted with carbonyl compounds of
the formula 31in which R.sup.3 represent alkyl having 1 to 4 carbon
atoms or represents phenyl and R.sup.4 represents hydrogen or alkyl
having 1 to 4 carbon atoms or R.sup.3 and R.sup.4 together
represent a --(CII.sub.2).sub.5- chain and with thiocyanate of the
formulaX-SCN (IV),in which X represents sodium, potassium or
ammonium, if appropriate in the presence of a diluent and if
appropriate in the presence of an acid, and b) the resulting
triazolidinethione derivatives of the formula 32in which R.sup.1,
R.sup.2, R.sup.3 and R.sup.4 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)-1-(2-chloro-phenyl)-2-hydroxy-p-
ropyl-1-hydrazine of the formula 33
3. Process according to claim 1, characterized in that for carrying
out the first step carbonyl compounds of the formula (III) are
employed in which R.sup.3 represents methyl, ethyl, n-propyl,
isopropyl, n-butyl, tert-butyl or phenyl and R.sup.4 represents
hydrogen, methyl, ethyl, n-propyl or n-butyl or R.sup.3 and R.sup.4
together represent a --(CH.sub.2).sub.5-chain.
4. Process according to claim 1, characterized in that the reaction
component used for carrying out the first step is sodium
thiocyanate or potassium thiocyanate.
5. Process according to claim 1, characterized in that the first
step is carried out at temperatures between 0.degree. C. and
120.degree. C.
6. Process according to claim 1, characterized in that the second
step of the process according to the invention is carried out at
temperatures between 80.degree. C. and 150.degree. C.
7. Triazolidinethione derivatives of the formula 34in 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, R.sup.3 represents alkyl having 1 to 4 carbon atoms or
phenyl and R.sup.4 represents hydrogen or alkyl having 1 to 4
carbon atoms or R.sup.3 and R.sup.4 together represent a
--(CH.sub.2).sub.5- chain.
8. Process for preparing triazolinethione derivatives of the
formula 35in 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 36or oxirane
derivative of the formula 37in 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 38in which R.sup.1 and R.sup.2 are each
as defined above are reacted without prior isolation with carbonyl
compounds of the formula 39in which R.sup.3 represents alkyl having
1 to 4 carbon atoms or represents phenyl and R.sup.4 represents
hydrogen or alkyl having 1 to 4 carbon atoms or R.sup.3 and R.sup.4
together represent a --(CH.sub.2).sub.5- chain and with thiocyanate
of the formulaX-SCN (IV),in which X represents sodium, potassium or
ammonium, if appropriate in the presence of a diluent and if
appropriate in the presence of an acid, and the resulting
triazolidinethione derivatives of the formula 40in which R.sup.1,
R.sup.2, R.sup.3 and R.sup.4 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.
9. Triazolidinethione derivative according to claim 7,
characterized by the formula 41
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 call
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-cyclopropyl)-1-(2-chloro-
-phenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol is obtained with
[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] 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, can be prepared by
[0009] a) reacting, in a first step, hydrazine derivatives of the
formula 6
[0010] in which
[0011] R.sup.1 and R.sup.2 are each as defined above with carbonyl
compounds of the formula 7
[0012] in which
[0013] R.sup.3 represents alkyl having 1 to 4 carbon atoms or
represents phenyl and
[0014] R.sup.4 represents hydrogen or alkyl having 1 to 4 carbon
atoms or
[0015] R.sup.3 and R.sup.4 together represent a --(CH.sub.2).sub.5-
chain and with thiocyanate of the formula
X--SCN (IV),
[0016] in which
[0017] X represents sodium, potassium or ammonium,
[0018] if appropriate in the presence of a diluent and if
appropriate in the presence of an acid, and
[0019] b) reacting the resulting triazolidinethione derivatives of
the formula 8
[0020] in which
[0021] R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each as defined
above
[0022] with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent.
[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 more
simple conditions than by the prior art methods. It is also
unexpected that, when the second step of the process according to
the invention is carried out, the exchange of the 9
[0024] for a methylene group occurs with high selectivity.
[0025] 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. Finally, 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.
[0026] Using
2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-
-1-hydrazine as starting material and reacting this in the first
step with acetone and potassium thiocyanate and, in the second
step, allowing the resulting triazolidinethione derivative to react
with formic acid, the course of the process according to the
invention can be illustrated by the formula scheme below. 10
[0027] 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
[0028] 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,
[0029] or
[0030] 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,
[0031] or
[0032] 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,
[0033] or
[0034] 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,
[0035] or
[0036] 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,
[0037] or
[0038] 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 unsubstituted 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,
[0039] or
[0040] 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,
[0041] 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
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
[0043] 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,
[0044] or
[0045] 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,
[0046] or
[0047] 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,
[0048] or
[0049] 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,
[0050] or
[0051] 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,
[0052] or
[0053] 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,
[0054] or
[0055] 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,
[0056] or
[0057] 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 to 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.
[0058] Particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0059] 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,
[0060] or
[0061] 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,
[0062] or
[0063] 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,
[0064] or
[0065] 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,
[0066] or
[0067] 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,
[0068] or
[0069] 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,
[0070] or
[0071] 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,
[0072] or
[0073] 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
[0074] 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,
[0075] or
[0076] 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,
[0077] 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,
[0078] or
[0079] 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,
[0080] or
[0081] 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,
[0082] or
[0083] 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,
[0084] or
[0085] 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,
[0086] or
[0087] 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.
[0088] Very particular preference is given to using hydrazine
derivatives of the formula (II) in which
[0089] 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,
[0090] or
[0091] 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,
[0092] or
[0093] 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,
[0094] or
[0095] 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,
[0096] or
[0097] 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,
[0098] or
[0099] 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,
[0100] or
[0101] 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,
[0102] or
[0103] 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
[0104] 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,
[0105] or
[0106] 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,
[0107] or
[0108] represents 1-methyl-cyclohexyl, cyclohexyl,
1-chloro-cyclopropyl, 1-fluoro-cyclopropyl, methyl-cyclopropyl,
1-cyano-cyclopropyl, cyclopropyl, 1-methyl-cyclopentyl or
1-ethyl-cyclopentyl,
[0109] or
[0110] 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,
[0111] or
[0112] 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,
[0113] or
[0114] represents phenoxyalkyl having 1 to 4 carbon atoms in the
straight-chain or branched oxyalkyl moiety, where the phenyl moiety
may be mono- to trisustittuted 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 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,
[0117] 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.
[0118] The hydrazine derivatives of the formula (II) are known or
can be prepared by processes known in principle (cf. DE-A-40 30
039).
[0119] Thus, hydrazine derivatives of the formula (II) are obtained
by reacting 1-chloro-2-hydroxy-ethane derivatives of the formula
11
[0120] or oxirane derivatives of the formula 12
[0121] in which
[0122] R.sup.1 and R.sup.2 are each as defined above with hydrazine
hydrate, if appropriate in the presence of a diluent.
[0123] The 1-chloro-2-hydroxy-ethane derivatives of the formula
(VI) and also the oxirane derivatives of the formula (VII) are
known or can be prepared by processes known in principle (cf.
DE-A-40 30 039 and EP-A 0 2397 345).
[0124] 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.
[0125] 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.
[0126] 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 (VI) or
of oxirane derivative or the formula (VII). 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 lease is removed
and the organic phase is washed and dried.
[0127] The formula (III) provides a general definition of the
carbonyl compounds required as reaction components for carrying out
the first step of the process according to the invention.
Preference is given to using carbonyl compounds of the formula
(III) in which
[0128] R.sup.3 represents methyl, ethyl, n-propyl, isopropyl,
n-butyl, tert-butyl or phenyl and
[0129] R.sup.4 represents hydrogen, methyl, ethyl, n-propyl or
n-butyl or
[0130] R.sup.3 and R.sup.4 together represent a --(CH.sub.2).sub.5-
chain.
[0131] Particular preference is given to carbonyl compounds of the
formula (III) in which
[0132] R.sup.3 represents methyl, ethyl, n-propyl, isopropyl,
tert-butyl or phenyl and
[0133] R.sup.4 represents hydrogen, methyl, ethyl or n-propyl
or
[0134] R.sup.3 and R.sup.4 together represent a --(CH.sub.2).sub.5-
chain.
[0135] Examples of carbonyl compounds of the formula (III) which
may be mentioned are:
[0136] acetaldehyde
[0137] propionaldehyde
[0138] benzaldehyde
[0139] acetone
[0140] diethyl ketone
[0141] methyl ethyl ketone
[0142] di-n-propyl ketone
[0143] pinacolone
[0144] acetophenone and
[0145] cyclohexanone.
[0146] The carbonyl compounds of the formula (III) and also the
thiocyanates of the formula (IV) are known.
[0147] 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, methyl tert-butyl ether,
1,2-dimethoxy-ethane or methyl tert-amyl ether, moreover esters,
such as ethyl acetate or butyl acetate, and also alcohols, such as
propanol, butanol or pentanol. However, excess carbonyl compound of
the formula (III) may also act as diluent.
[0148] Suitable acids for carrying out the first step of the
process according to the invention are customary inorganic or
organic acids. Preference is given to using hydrochloric acid,
sulphuric acid or p-toluenesulphonic acid.
[0149] 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 0.degree. C. and 120.degree. C., preferably
between 10.degree. C. and 110.degree. C.
[0150] 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 are involved in the reaction,
under reduced pressure.
[0151] When carrying out the first step of the process according to
the invention, generally 1 to 2 mol of carbonyl compound of the
formula (III) and 1 to 2 mol of thiocyanate of the formula (IV) 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
recrystallization.
[0152] The formula (V) provides a general definition of the
triazolidinethione derivatives required as starting materials for
carrying out the second step of the process according to the
invention. In this formula, R.sup.1, R.sup.2, R.sup.3 and R.sup.4
each preferably have those meanings which have already been
mentioned in connection with the description of the hydrazine
derivatives of the formula (II) or the carbonyl compounds of the
formula (III) as being preferred for these radicals.
[0153] The triazolidinethione derivatives of the formula (V) have
hitherto not been disclosed. They can be prepared by the reaction
of the first step of the process according to the invention.
[0154] 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, sulphuric acid or
p-toluenesulphonic acid, and also metal oxides, such as amorphous
titanium dioxide.
[0155] 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 alcohols, such as propanol, butanol or pentanol,
furthermore esters, such as ethyl acetate, butyl acetate or
isobutyl formate, moreover ethers, such as 1,2-dimethoxyethane,
methyl tert-butyl ether or methyl tert-amyl ether, and also an
excess of formic acid.
[0156] When carrying out the second step of the process according
to the invention, the reaction temperature can be varied within a
certain range. In general, the reaction is carried out at
temperatures between 90.degree. C. and 150.degree. C., preferably
between 90.degree. C. and 130.degree. C.
[0157] When carrying out the second step of the process according
to the invention, an excess, in general from 5 to 50 mol, of formic
acid and, if appropriate, a small amount of catalyst is employed
per mole of triazolidinethione derivative of the formula (V).
Work-up is 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 hydrochloric acid, and the organic phase is dried and
concentrated. Any impurities which may then still be present call
be removed by customary methods, such as recrystallization.
[0158] 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) or oxirane derivatives of the
formula (VII) are reacted with hydrazine hydrate and the resulting
hydrazine derivatives of the formula (II) are then reacted further
without prior isolation and purification. Accordingly,
triazolinethione derivatives of the formula (I) can also be
prepared by
[0159] reacting 1-chloro-2-hydroxy-ethane derivatives of the
formula 13
[0160] or oxirane derivatives of the formula 14
[0161] R.sup.1 and R.sup.2 are each as defined above
[0162] with hydrazine hydrate, if appropriate in the presence of a
diluent, and reacting the resulting
[0163] hydrazine derivatives of the formula 15
[0164] in which
[0165] R.sup.1 and R.sup.2 are each as defined above
[0166] without prior isolation with carbonyl compounds of the
formula 16
[0167] in which
[0168] R.sup.3 represents alkyl having 1 to 4 carbon atoms or
represents phenyl and
[0169] R.sup.4 represents hydrogen or alkyl having 1 to 4 carbon
atoms or
[0170] R.sup.3 and R.sup.4 together represent a --(CH.sub.2).sub.5-
chain, and with thiocyanate of the formula
X-SCN (IV)
[0171] in which
[0172] X represents sodium, potassium or ammonium,
[0173] if appropriate in the presence of a diluent and if
appropriate in the presence of an acid, and
[0174] reacting the resulting triazolidinethione derivatives of the
formula 17
[0175] in which
[0176] R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each as defined
above
[0177] with formic acid, if appropriate in the presence of a
catalyst and if appropriate in the presence of a diluent.
[0178] The individual steps of this process are carried out in the
manner already described above.
[0179] The triazolinethione derivatives preparable according to the
invention can be present in the "thiono" form of the formula 18
[0180] or in the tautomeric "mercapto" form of the formula 19
[0181] For the sake of simplicity, only the "thiono" form is shown
in each case.
[0182] The triazolinethione derivatives preparable according to the
invention are known as active compounds having microbicidal, in
particular fungicidal, properties (cf. WO-A 96-16 048).
[0183] The practice of the process according to the invention is
illustrated by the examples below.
Preparation Examples
Example 1
[0184] 20
[0185] a) Preparation of the compound of the formula 21
[0186] At room temperature and with stirring, a mixture of 27.5 g
(0.1 mol) of
2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-h-
ydrazine and 300 ml of 2N aqueous hydrochloric acid is initially
admixed with 8.2 g (0.14 mol) of acetone and then with 13.6 g (0.14
mol) of potassium thiocyanate. The reaction mixture is then admixed
with 100 ml of toluene and stirred at room temperature for another
10 hours. The resulting solid is then filtered off, washed with
water and then with toluene and dried. In this manner, 30.7 g
(82.1% of theory) of the triazolidinethione derivative are obtained
in the form of a colourless crystalline solid of meting point 186
to 189.degree. C.
[0187] b) Preparation of the compound of the formula 22
[0188] At room temperature and with stirring, a mixture of 92 g of
formic acid and 100 l ml of isobutyl formate is admixed with 18.7 g
(0.05 mol) of the triazolidinethione derivative described under a).
After the addition has ended, the reaction mixture is heated under
reflux for 17 hours, then concentrated by distilling off excess
formic acid and solvent and finally freed of volatile components
under high vacuum. The product that remains is dissolved in toluene
the resulting solution is washed with water, and the organic phase
is dried over sodium sulphate and concentrated by distilling off
the solvent. In this manner, 14.2 g (76% of theory) of
2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-
-1,2,4-triazole-5-thiono-1-yl)-propyl-2-ol are obtained in the form
of a solid of melting point 138 to 139.degree. C.
Example 2
[0189] 23
[0190] At room temperature and with stirring, 22 g (=0.05 mol) of a
product comprising 63.7% of 1-chloro-2-hydroxy-ethane are added
dropwise over a period of 15 minutes to 25 g (0.5 mol) of hydrazine
hydrate. After the addition has ended, the reaction mixture is
stirred at 100.degree. C. for 2 hours and then cooled to room
temperature. The resulting mixture is stirred into 100 ml of water
and the aqueous phase is decanted off from the solid precipitate.
This process is repeated once more using 100 ml of water. The
resulting product is admixed with 150 ml of 2N aqueous hydrochloric
acid, 4.1 g (0.07 mol) of acetone, 6.8 g (0.07 mol) of potassium
thiocyanate and 50 ml of toluene. The reaction mixture is stirred
at room temperature for 12 hours and then filtered. The filter
residue is washed successively with water and toluene and then
dried. In this manner, 11.6 g of triazolidinethione derivative of
the abovementioned formula are obtained in tie form of a colourless
crystalline solid of melting point 186 to 187.degree. C. The
calculated yield is 62.0% of theory, based on the
1-chloro-2-hydroxy-ethane employed.
[0191] The triazolidinethione derivatives listed in the table below
are likewise prepared by the method given in Example 2.
1TABLE 1 24 (Va) Ex. Melting point Yield in % of No. R.sup.3
R.sup.4 [.degree. C.] theory 3 --CH.sub.3 H 143-146 52.6 4
--CH.sub.3 --C.sub.2H.sub.5 167 (decomp.) 72.5 5 25 --CH.sub.3 174
(decomp.) 66.4 6 --(CH.sub.2).sub.5-- 194-196 67.9 (decomp.) 7
--C(CH.sub.3).sub.3 --CH.sub.3 137 (decomp.) 59.3 8
--CH(CH.sub.3).sub.2 --CH.sub.3 146-152 68.2 9 26 H 176 38
Comparative Examples
[0192] Example A 27
[0193] 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-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-cyclopropyl)-1--
(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-ol
are obtained. Recrystallization from toluene gives this substance
as a solid which melts at from 138 to 139.degree. C.
Example B
[0194] 28
[0195] 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-ol, 0.95 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-
ophenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-ol is
obtained in the form of a solid which melts at 138-139.degree.
C.
* * * * *