U.S. patent application number 09/791688 was filed with the patent office on 2001-08-09 for substituted thiopyridines.
Invention is credited to Gebhardt, Joachim, Hamprecht, Gerhard, Isak, Heinz, Rack, Michael, Rheinheimer, Joachim, Schafer, Peter.
Application Number | 20010012897 09/791688 |
Document ID | / |
Family ID | 7805316 |
Filed Date | 2001-08-09 |
United States Patent
Application |
20010012897 |
Kind Code |
A1 |
Hamprecht, Gerhard ; et
al. |
August 9, 2001 |
Substituted thiopyridines
Abstract
Substituted thiopyridines of the general formula I 1 where n is
1 or 2; R.sup.1 is chlorine, C.sub.1-C.sub.3-fluoroalkyl, nitro or
methylsulfonyl; R.sup.2 is a C.sub.1-C.sub.10-alkyl,
C.sub.2-C.sub.10-alkenyl or C.sub.2-C.sub.10-alkynyl radical, in
each case unsubstituted or substituted by halogen,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkoxycar- bonyl,
di-(C.sub.1-C.sub.4-alkylamino)carbonyl, cyano or nitro, a
C.sub.3-C.sub.8-cycloalkyl radical, or a
C.sub.1-C.sub.4-alkylenephenyl, phenyl or naphthyl radical which is
unsubstituted or substituted in the phenyl moiety by halogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy, trifluoromethyl,
cyano or nitro.
Inventors: |
Hamprecht, Gerhard;
(Weinheim, DE) ; Gebhardt, Joachim; (Wachenheim,
DE) ; Isak, Heinz; (Bohl-Iggelheim, DE) ;
Rack, Michael; (Heidelberg, DE) ; Rheinheimer,
Joachim; (Ludwigshafen, DE) ; Schafer, Peter;
(Ottersheim, DE) |
Correspondence
Address: |
HERBERT B. KEIL
KEIL & WEINKAUF
1101 Connecticut Avenue, N.W.
Washington
DC
20036
US
|
Family ID: |
7805316 |
Appl. No.: |
09/791688 |
Filed: |
February 26, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09791688 |
Feb 26, 2001 |
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09254569 |
Mar 10, 1999 |
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09254569 |
Mar 10, 1999 |
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PCT/EP97/04707 |
Aug 29, 1997 |
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Current U.S.
Class: |
546/294 |
Current CPC
Class: |
C07D 213/71
20130101 |
Class at
Publication: |
546/294 |
International
Class: |
C07D 211/96 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 12, 1996 |
DE |
19636997.5 |
Claims
We claim:
1. A substituted thiopyridine of the general formula I 22where n is
1 or 2; R.sup.1 is chlorine, trifluoromethyl or difluoromethyl;
R.sup.2 is a C.sub.1-C.sub.8-alkyl radical which is unsubstituted
or substituted by chlorine or methoxy, or a benzyl or phenyl
radical which is unsubstituted or substituted in the phenyl moiety
by chlorine, methyl, methoxy or trifluoromethyl, with the exception
of the compound: 3,5-dichloro-2-methylsulfinylpyridine.
2. A process for the preparation of thiopyridines of the general
formula Ib 23as claimed in claim 1, which comprises reacting a
3-chloro-2-halopyridine of the formula II, 24where R.sup.1 has the
meaning mentioned in claim 1 and Hal is fluorine, chlorine or
bromine, with a thio compound of the formula III
H[O].sub.mS(.dbd.O).sub.n--R.sup.- 2 III where R.sup.2 has the
meaning mentioned in claim 1 and m and n are 0, or an alkali metal
or alkaline earth metal salt thereof, in the presence or absence of
a base, to give the pyridine thioether Ia, 25and subsequently
treating the latter with an oxidant.
3. A process for the preparation of thiopyridines of the general
formula Ic 26as claimed in claim 1, which comprises reacting a
3-chloro-2-halopyridine of the formula II, 27where R.sup.1 has the
meaning mentioned in claim 1 and Hal is fluorine, chlorine or
bromine, with a thio compound of the formula III or with an alkali
metal or alkaline earth metal salt thereof
H[O].sub.mS(.dbd.O).sub.n--R.sup.2 III where R.sup.2 in formula III
has the meaning mentioned in claim 1 and m and n are 0 or 1, and,
in the event that m and n have the value 0, subsequently treating
the product of this reaction with an oxidant.
4. A process as claimed in either of claims 3 and 4, wherein the
oxidation of the pyridine thioethers Ia to give the thiopyridines I
is effected with the aid of hydrogen peroxide in a mixture of
acetic acid and trifluoroacetic acid in a ratio of 6:1 to 4:1 by
volume.
5. A process as claimed in either of claims 3 and 4, wherein the
oxidation of the pyridine thioethers Ia to give the thiopyridines I
is effected with the aid of hypochlorous acid and an alkali metal
salt thereof.
6. A pyridine thioether of the general formula Ia 28where R.sup.1
is chlorine, trifluoromethyl or difluoromethyl; R.sup.2 is a
C.sub.1-C.sub.8-alkyl radical which is unsubstituted or substituted
by chlorine or methoxy, or a benzyl or phenyl radical which is
unsubstituted or substituted in the phenyl moiety by chlorine,
methyl, methoxy or trifluoromethyl, with the exception of the
compounds:
2-(2-methyl-4-methoxyphenylthio)-3-chloro-5-trifluoromethylpyridine
and
2-(3-methyl-4-methoxyphenylthio)-3-chloro-5-trifluoromethylpyridine.
7. The use of the pyridine thioethers of the formula Ia as
intermediates for the preparation of the thiopyridines I as claimed
in claim 1.
Description
DESCRIPTION
[0001] The invention relates to novel thiopyridines of the general
formula I 2
[0002] where
[0003] n is 1 or 2;
[0004] R.sup.1 is chlorine, C.sub.1-C.sub.3-fluoroalkyl, nitro or
methylsulfonyl;
[0005] R.sup.2 is a C.sub.1-C.sub.10-alkyl,
C.sub.2-C.sub.10-alkenyl or C.sub.2-C.sub.10-alkynyl radical, in
each case unsubstituted or substituted by halogen,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkoxycar- bonyl,
di-(C.sub.1-C.sub.4-alkylamino) carbonyl, cyano or nitro, a
C.sub.3-C.sub.8-cycloalkyl radical, or a
C.sub.1-C.sub.4-alkylenephenyl, phenyl or naphthyl radical which is
unsubstituted or substituted in the phenyl moiety by halogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy, trifluoromethyl,
cyano or nitro.
[0006] Moreover, the invention relates to processes for their
preparation and to their use as intermediates for the preparation
of herbicidally active crop protection agents, as they are
disclosed in WO-A-95/02580. The invention furthermore relates to
the pyridine thioethers of the formula Ia, which are suitable for
the preparation of the thiopyridines I, as intermediates. 3
[0007] 2-(3-Nitrophenylthio), 2-(2-methyl-4-methoxyphenylthio) and
2-(2-nitrobenzylthio)pyridines which have a further chlorine, or
trifluoromethyl or methylsulfonyl radical, in the 5-position and a
chlorine substituent in the 3-position have already been disclosed
in the literature (EP 320 448, J5 6029-504, EP 498 396).
[0008] 3-Fluoropyridines which are correspondingly substituted are
disclosed in U.S. Pat. No. 4,983,211.
[0009] The thiopyridines mentioned in the above publications are
used as herbicides or fungicides, or as intermediates for
herbicides, the function which is responsible for the herbicidal
action in the end molecule being synthesized in each case via the
thio substituent, which thus remains in the end molecule.
[0010] It is an object of the present invention to provide novel
thiopyridine derivatives which are suitable as coupling components
for the preparation of substituted phenylpyridines as they are
described in WO-A-95/02580. Here, the thio substituent acts as a
leaving group.
[0011] It is a further object of the present invention to provide a
process which makes the desired thiopyridines accessible in high
yields.
[0012] Accordingly, we have found the thiopyridines defined at the
outset, of the general formula I 4
[0013] where
[0014] n is 1 or 2;
[0015] R.sup.1 is chlorine, C.sub.1-C.sub.3-fluoroalkyl, nitro or
methylsulfonyl;
[0016] R.sup.2 is a C.sub.1-C.sub.10-alkyl,
C.sub.2-C.sub.10-alkenyl or C.sub.2-C.sub.10-alkynyl radical, in
each case unsubstituted or substituted by halogen,
C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-alkoxycar- bonyl,
di-(C.sub.1-C.sub.4-alkylamino)carbonyl, cyano or nitro, a
C.sub.3-C.sub.8-cycloalkyl radical, or a
C.sub.1-C.sub.4-alkylenephenyl, phenyl or naphthyl radical which is
unsubstituted or substituted in the phenyl moiety by halogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy, trifluoromethyl,
cyano or nitro. The meanings mentioned above for the substituent
R.sup.2 in formula I are collective terms for individual
enumerations of the individual group members. All carbon chains,
ie. all alkyl, alkenyl, alkynyl or alkoxy moieties, can be
straight-chain or branched.
[0017] Halogenated substituents preferably have attached to them
1-6 identical or different halogen atoms.
[0018] Examples of individual meanings are:
[0019] halogen
[0020] fluorine, chlorine, bromine and iodine, preferably fluorine
and chlorine;
[0021] C.sub.1-C.sub.3-alkyl
[0022] methyl, ethyl, n-propyl, 1-methylethyl;
[0023] C.sub.1-C.sub.10-alkyl
[0024] C.sub.1-C.sub.3-alkyl as mentioned above, and also n-butyl,
1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl, n-pentyl,
1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl,
1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl,
1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,
1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl,
2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl,
1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,
1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl; n-heptyl,
n-octyl, n-nonyl, n-decyl, 1-methylhexyl, l-ethylhexyl,
1-methylheptyl, 1-methyloctyl, 1-methylnonyl;
C.sub.2-C.sub.10-alkenyl ethenyl, prop-1-en-1-yl, prop-2-en-1-yl,
1-methylethenyl, n-buten-1-yl, n-buten-2-yl, n-buten-3-yl,
1-methylprop-1-en-1-yl, 2-methylprop-1-en-1-yl,
1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, n-penten-1-yl,
n-penten-2-yl, n-penten-3-yl, n-penten-4-yl, 1-methylbut-1-en-1-yl,
2-methylbut-1-en-1-yl, 3-methylbut-1-en-1-yl,
1-methylbut-2-en-1-yl, 2-methylbut-2-en-1-yl,
3-methylbut-2-en-1-yl, 1-methylbut-3-en-1-yl,
2-methylbut-3-en-1-yl, 3-methylbut-3-en-1-yl,
1,1-dimethylprop-2-en-1-yl, 1,2-dimethylprop-1-en-1-yl,
1,2-dimethylprop-2-en-1-yl, 1-ethylprop-1-en-2-yl,
1-ethylprop-2-en-1-yl, n-hex-1-en-1-yl, n-hex-2-en-1-yl,
n-hex-3-en-1-yl , n-hex-4-en-1-yl, n-hex-5-en-1-yl,
1-methylpent-1-en-1-yl, 2-methylpent-1-en-1-yl,
3-methylpent-1-en-1-yl, 4-methylpent-1-en-1-yl,
1-methylpent-2-en-1-yl, 2-methylpent-2-en-1-yl,
3-methylpent-2-en-1-yl, 4-methylpent-2-en-1-yl,
1-methylpent-3-en-1-yl, 2-methylpent-3-en-1-yl,
3-methylpent-3-en-1-yl, 4-methylpent-3-en-1-yl,
1-methylpent-4-en-1-yl, 2-methylpent-4-en-1-yl,
3-methylpent-4-en-1-yl, 4-methylpent-4-en-1-yl,
1,1-dimethylbut-2-en-1-yl, 1,1-dimethylbut-3-en-1-yl,
1,2-dimethylbut-1-en-1-yl, 1,2-dimethylbut-2-en-1-yl,
1,2-dimethylbut-3-en-1-yl, 1,3-dimethylbut-1-en-1-yl,
1,3-dimethylbut-2-en-1-yl, 1,3-dimethylbut-3-en-1-yl,
2,2-dimethylbut-3-en-1-yl, 2,3-dimethylbut-1-en-1-yl,
2,3-dimethylbut-2-en-1-yl, 2,3-dimethylbut-3-en-1-yl,
3,3-dimethylbut-1-en-1-yl, 3,3-dimethylbut-2-en-1-yl,
1-ethylbut-1-en-1-yl, 1-ethylbut-2-en-1-yl, 1-ethylbut-3-en-1-yl,
2-ethylbut-1-en-1-yl, 2-ethylbut-2-en-1-yl, 2-ethylbut-3-en-1-yl,
1,1,2-trimethylprop-2-en-1-yl, 1-ethyl-1-methylprop-2-en-1-yl,
1-ethyl-2-methylprop-1-en-1-yl and 1-ethyl-2-methylprop-2-en-1-yl,
hept-2-en-1-yl, oct-2-en-1-yl, non-2-en-1-yl, dec-2-en-1-yl,
preferably ethenyl and prop-2-en-1-yl;
[0025] C.sub.2-C.sub.10-alkynyl
[0026] ethynyl and C.sub.3-C.sub.6-alkynyl such as prop-1-yn-1-yl,
prop-2-yn-3-yl, n-but-1-yn-1-yl, n-but-1-yn-4-yl, n-but-2-yn-1-yl,
n-pent-1-yn-1-yl, n-pent-1-yn-3-yl, n-pent-1-yn-4-yl,
n-pent-1-yn-5-yl, n-pent-2-yn-1-yl, n-pent-2-yn-4-yl,
n-pent-2-yn-5-yl, 3-methylbut-1-yn-1-yl, 3-methyl-but-1-yn-3-yl,
3-methyl-but-1-yn-4-yl, n-hex-1-yn-1-yl, n-hex-1-yn-3-yl,
n-hex-1-yn-4-yl, n-hex-1-yn-5-yl, n-hex-1-yn-6-yl, n-hex-2-yn-1-yl,
n-hex-2-yn-4-yl, n-hex-2-yn-5-yl, n-hex-2-yn-6-yl, n-hex-3-yn-1-yl,
n-hex-3-yn-2-yl, 3-methylpent-1-yn-1-yl, 3-methyl-pent-1-yn-3-yl,
3-methylpent-1-yn-4-yl, 3-methylpent-1-yn-5-yl,
4-methylpent-1-yn-1-yl, 4-methylpent-2-yn-4-yl and
4-methylpent-2-yn-5-yl, hept-2-yn-1-yl, oct-2-yn-1-yl,
non-2-yn-1-yl, dec-2-yn-1-yl, preferably prop-2-yn-1-yl,
1-methylprop-2-yn-1-yl;
[0027] C.sub.1-C.sub.3-fluoroalkyl
[0028] C.sub.1-C.sub.3-alkyl as mentioned above, where in each case
1-5 hydrogen atoms are replaced by fluorine, eg. fluoromethyl,
difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl,
2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,
3,3,3-trifluoropropyl, preference is given to difluoromethyl,
trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,
3,3,3-trifluoropropyl, special preference is given to
trifluoromethyl;
[0029] C.sub.1-C.sub.10-haloalkyl
[0030] C.sub.1-C.sub.10-alkyl as mentioned above, where in each
case 1-6 hydrogen atoms are replaced by fluorine, chlorine and/or
bromine, ie., for example, chloromethyl, dichloromethyl,
trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,
chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl,
1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl,
2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl,
2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl,
2,2,2-trichloroethyl, pentafluoroethyl and 3-chloropropyl,
preferably trifluoromethyl;
[0031] C.sub.2-C.sub.10-haloalkenyl
[0032] C.sub.2-C.sub.10-alkenyl as mentioned above, where in each
case 1-6 hydrogen atoms are replaced by fluorine, chlorine and/or
bromine; C.sub.2-C.sub.10-haloalkynyl C.sub.2-C.sub.10-alkynyl as
mentioned above, where in each case one to six hydrogen atoms are
replaced by fluorine, chlorine and/or bromine;
[0033] C.sub.3-C.sub.8-cycloalkyl
[0034] cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,
cycloheptyl and cyclooctyl, preferably cyclopropyl, cyclopentyl and
cyclohexyl;
[0035] cyano-(C.sub.1-C.sub.10) -alkyl
[0036] C.sub.1-C.sub.10-alkyl as mentioned above, where in each
case one hydrogen atom is replaced by the cyano group, ie., for
example, cyanomethyl, 1-cyanoeth-1-yl, 2-cyanoeth-1-yl,
1-cyanoprop-1-yl, 2-cyanoprop-1-yl, 3-cyanoprop-1-yl,
1-cyanoprop-2-yl, 2-cyanoprop-2-yl, 1-cyanobut-1-yl,
2-cyanobut-1-yl, 3-cyanobut-1-yl, 4-cyanobut-1-yl, 1-cyanobut-2-yl,
2-cyanobut-2-yl, 1-cyanobut-3-yl, 2-cyanobut-3-yl,
1-cyano-2-methyl-prop-3-yl, 2-cyano-2-methyl-prop-3-yl,
3-cyano-2-methyl-prop-3-yl, and 2-cyanomethyl-prop-2-yl,
6-cyanohex-1-yl, 7-cyanohept-1-yl, 8-cyanooct-1-yl,
9-cyanonon-1-yl, 10-cyanodec-1-yl; preferably cyanomethyl,
1-cyano-1-methylethyl;
[0037] C.sub.1-C.sub.4-alkoxy and the alkoxy moieties of
C.sub.1-C.sub.4-alkoxycarbonyl, methoxy, ethoxy, n-propoxy,
1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy and
1,1-dimethyl- ethoxy, preferably methoxy, ethoxy and
1-methylethoxy;
[0038] di-(C.sub.1-C.sub.4-alkyl) aminocarbonyl
[0039] N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl,
N,N-dipropylaminocarbonyl, N,N-di-(1-methylethyl)aminocarbonyl,
N,N-dibutylaminocarbonyl, N,N-di-(1-methylpropyl)aminocarbonyl,
N,N-di-(2-methylpropyl)aminocarbonyl,
N,N-di-(1,1-dimethylethyl)aminocarb- onyl,
N-ethyl-N-methylaminocarbonyl, N-methyl-N-propylaminocarbonyl,
N-methyl-N-(1-methylethyl)aminocarbonyl,
N-butyl-N-methylaminocarbonyl,
N-methyl-N-(1-methylpropyl)aminocarbonyl,
N-methyl-N-(2-methylpropyl)amin- ocarbonyl,
N-(1,1-di-methylethyl)-N-methylaminocarbonyl,
N-ethyl-N-propylaminocarbonyl,
N-ethyl-N-(1-methylethyl)aminocarbonyl,
N-butyl-N-ethylaminocarbonyl,
N-ethyl-N-(1-methylpropyl)aminocarbonyl,
N-ethyl-N-(2-methylpropyl)aminocarbonyl,
N-ethyl-N-(1,1-dimethylethyl)ami- nocarbonyl,
N-(1-methylethyl)-N-propylaminocarbonyl,
N-butyl-N-propylaminocarbonyl,
N-(1-methylpropyl)-N-propylaminocarbonyl,
N-(2-methylpropyl)-N-propylamino-carbonyl,
N-(1,1-dimethylethyl)-N-propyl- aminocarbonyl,
N-butyl-N-(1-methylethyl)aminocarbonyl,
N-(1-methylethyl)-N-(1-methylpropyl)aminocarbonyl,
N-(1-methylethyl)-N-(2-methylpropyl) aminocarbonyl,
N-(1,1-dimethylethyl)-N-(1-methylethyl)aminocarbonyl,
N-butyl-N-(1-methylpropyl)aminocarbonyl,
N-butyl-N-(2-methylpropyl)aminoc- arbonyl,
N-butyl-N-(1,1-dimethylethyl)aminocarbonyl,
N-(1-methylpropyl)-N-(2-methylpropyl)aminocarbonyl,
N-(1,1-dimethylethyl)-N-(1-methylpropyl)aminocarbonyl and
N-(1,1-dimethylethyl)-N-(2-methylpropyl)aminocarbonyl, preferably
dimethylaminocarbonyl and diethylaminocarbonyl;
[0040] C.sub.1-C.sub.4-alkylene
[0041] methylene, ethylene, propylene, 1-methylethylene, butylene,
1,2-dimethylethylene and 1-ethylethylene;
[0042] 1-phenyl which is unsubstituted or substituted by halogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy, trifluoromethyl,
cyano or nitro 2-, 3-, 4-chlorophenyl, 2-, 3-, 4-tolyl,
2-chloro-4-methylphenyl, 2,4-dichlorophenyl, 2,4,6-trichlorophenyl,
2,6-dichloro-4-methylphenyl, 2-, 3-, 4-methoxyphenyl,
2-chloro-4-methoxyphenyl, 3-chloro-4-methoxyphenyl, 2-, 3-,
4-trifluoromethylphenyl, 2-, 3-, 4-cyanophenyl, 2-, 3-,
4-nitrophenyl, 2-methyl-4-nitrophenyl,
2-chloro-4-trifluoromethylphenyl, 2-chloro-4-nitrophenyl and
unsubstituted phenyl.
[0043] Preferred amongst the compounds I are those where
[0044] n is 1 or 2;
[0045] R.sup.1 is chlorine, nitro or C.sub.1-C.sub.3-fluoroalkyl;
30
[0046] R.sup.2 is a C.sub.1-C.sub.8-alkyl, C.sub.2-C.sub.8-alkenyl
or C.sub.3-C.sub.8-alkynyl radical, unsubstituted or substituted by
halogen or C.sub.1-C.sub.4-alkoxy, an unsubstituted
C.sub.3-C.sub.8-cycloalkyl radical, or a benzyl or phenyl radical,
unsubstituted or substituted in the phenyl moiety by halogen,
C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy, nitro, cyano or
trifluoromethyl.
[0047] Especially preferred compounds I are those where
[0048] n is 1 or 2;
[0049] R.sup.1 is chlorine, trifluoromethyl or difluoromethyl;
[0050] R.sup.2 is a C.sub.1-C.sub.8-alkyl radical, unsubstituted or
substituted by chlorine or methoxy, or a benzyl or phenyl radical,
unsubstituted or substituted in the phenyl moiety by chlorine,
methyl, methoxy or trifluoromethyl.
[0051] Individual examples which may be mentioned are the following
pyridine thioethers Ia of Tables 1-4, the pyridine sulfoxides Ib of
Tables 5-8 and the pyridine sulfones Ic of Tables 9-12.
[0052] Preferred are the pyridine thioethers I.001-1.116 of the
formula Ia1 5
[0053] which are given in Table 1.
1 TABLE 1 No. R.sup.2 Ia1.001 CH.sub.3 Ia1.002 C.sub.2H.sub.5
Ia1.003 n-C.sub.3H.sub.7 Ia1.004 i-C.sub.3H.sub.7 Ia1.005
n-C.sub.4H.sub.9 Ia1.006 sec-C.sub.4H.sub.9 Ia1.007
i-C.sub.4H.sub.9 Ia1.008 tert-C.sub.4H.sub.9 Ia1.009
n-C.sub.5H.sub.11 Ia1.010 sec-C.sub.5H.sub.11 Ia1.011
CH.sub.2--CH.sub.2--CH(CH.sub- .3).sub.2 Ia1.012
CH.sub.2--CH(CH.sub.3)--CH.sub.2--CH.sub.3 Ia1.013
CH(CH.sub.3)--CH(CH.sub.3).sub.2 Ia1.014 CH(C.sub.2H.sub.5).sub.2
Ia1.015 n-C.sub.6H.sub.13 Ia1.016 sec-C.sub.6H.sub.13 Ia1.017
CH(C.sub.2H.sub.5)-n-C.sub.3H- .sub.7 Ia1.018
CH(CH.sub.3)--CH(CH.sub.3)--C.sub.2H.sub.5 Ia1.019
n-C.sub.7H.sub.15 Ia1.020 sec-C.sub.7--H.sub.15 Ia1.021
CH(C.sub.2H.sub.5)-n-C.sub.4H.sub.9 Ia1.022
CH(CH.sub.3)--CH(CH.sub.3)-n-C.sub.3H.sub.7 Ia1.023
n-C.sub.8H.sub.17 Ia1.024 sec-C.sub.8H.sub.17 Ia1.025
CH(C.sub.2H.sub.5)-n-C.sub.5H.sub.11 Ia1.026 n-C.sub.9H.sub.19
Ia1.027 sec-C.sub.9H.sub.19 Ia1.028 CH(C.sub.2H.sub.5)-n-C.s-
ub.6H.sub.13 Ia1.029 n-C.sub.10H.sub.21 Ia1.030
sec-C.sub.10H.sub.21 Ia1.031 CH.sub.2--CH.sub.2--O--CH.sub.3
Ia1.032 CH.sub.2--CH.sub.2--O--C.sub.2H.sub.5 Ia1.033
CH.sub.2--CH(OCH.sub.3)--CH.sub.3 Ia1.034 (CH.sub.2).sub.3--O--CH-
.sub.3 Ia1.035 (CH.sub.2).sub.3--O--C.sub.2H.sub.5 Ia1.036
(CH.sub.2).sub.4--O--CH.sub.3 Ia1.037 CH.sub.2CH.sub.2Cl Ia1.038
(CH.sub.2).sub.3Cl Ia1.039 (CH.sub.2).sub.4Cl IaI.040 cyclopropyl
Ia1.041 cyclobutyl Ia1.042 cyclopentyl Ia1.043 cyclohexyl Ia1.044
cycloheptyl Ia1.045 cyclooctyl Ia1.046 CH.sub.2.dbd.CH.sub.2
Ia1.047 CH.sub.2--CH.dbd.CH.sub.2 Ia1.048
CH.sub.2CH.dbd.CH--CH.sub.3 Ia1.049 CH(CH.sub.3)--CH.dbd.CH.sub.2
Ia1.050 CH.sub.2--CH.sub.2--C(CH.sub.3).dbd.CH.sub.2 Ia1.052
CH.sub.2CH.dbd.C(CH.sub.3).sub.2 Ia1.052 C(CH.sub.3).sub.2--CH.db-
d.CH.sub.2 Ia1.053 CH.sub.2--C.ident.CH Ia1.054
CH.sub.2--C.ident.C--CH.sub.3 Ia1.055 CH(CH.sub.3)--C.ident.CH
Ia1.056 C(CH.sub.3).sub.2--C.ident.CH Ia1.057
C(C.ident.CH)--CH(C.sub.2H.sub.5)-n-C.sub.4H.sub.9 Ia1.058
CH.sub.2--CH.sub.2--CN Ia1.059 (CH.sub.2).sub.3CN Ia1.060
CH.sub.2CH.sub.2NO.sub.2 Ia1.061 (CH.sub.2).sub.3NO.sub.2 Ia1.062
phenyl Ia1.063 2-chlorophenyl Ia1.064 3-chlorophenyl Ia1.065
4-chlorophenyl Ia1.066 2,3-dichlorophenyl Ia1.067
2,4-dichlorophenyl Ia1.068 2,5-dichlorophenyl Ia1.069
2,6-dichlorophenyl Ia1.070 2,4,6-trichlorophenyl Ia1.071 2-tolyl
Ia1.072 3-tolyl Ia1.073 4-tolyl Ia1.074 2-chloro-4-tolyl Ia1.075
2,6-dichloro-4-tolyl Ia1.076 4-chloro-2-tolyl Ia1.077
4,6-dichloro-2-tolyl Ia1.078 2-methoxyphenyl Ia1.079
3-methoxyphenyl Ia1.080 4-methoxyphenyl Ia1.081
2-chloro-4-methoxyphenyl Ia1.082 2,6-dichloro-4-methoxyphenyl
Ia1.083 4-chloro-2-methoxyphenyl Ia1.084
4,6-dichloro-2-methoxyphenyl Ia1.085 2-nitrophenyl Ia1.086
3-nitrophenyl Ia1.087 4-nitrophenyl Ia1.088 4-methyl-2-nitrophenyl
Ia1.089 4-chloro-2-nitrophenyl Ia1.090 4-methoxy-2-nitrophenyl
Ia1.091 2-trifluoromethylphenyl Ia1.092 3-trifluoromethylphenyl
Ia1.093 4-trifluoromethylphenyl Ia1.094
2-chloro-4-trifluoromethylphenyl Ia1.095
4-chloro-2-trifluoromethylphenyl Ia1.096 2-cyanophenyl Ia1.097
3-cyanophenyl Ia1.098 4-cyanophenyl Ia1.099 2-methyl-4-nitrophenyl
Ia1.100 5-methyl-2-nitrophenyl Ia1.101 1-naphthyl Ia1.102
2-naphthyl Ia1.103 4-methyl-1-naphthyl Ia1.104 4-chloro-1-naphthyl
Ia1.105 benzyl Ia1.106 2-methylbenzyl Ia1.107 3-methylbenzyl
Ia1.108 4-methylbenzyl Ia1.109 2-chlorobenzyl Ia1.110
3-chlorobenzyl Ia1.111 4-chlorobenzyl Ia1.112 2,4-dichlorobenzyl
Ia1.113 2,4,6-trichlorobenzyl Ia1.114 2-trifluoromethylbenzyl
Ia1.115 3-trifluoromethylbenzyl Ia1.116 4-trifluoromethylbenzyl
TABLE 2
[0054] Furthermore preferred are the pyridine thioethers
Ia2.001-Ia2.085 and Ia2.087-Ia2.116 of the formula Ia2, which
differ from the compounds Ia1.001-Ia1.085 and Ia1.087-Ia1.116 in
that, instead of chlorine, a trifluoromethyl group is attached to
the pyridine ring in the 5-position. 6
TABLE 3
[0055] Furthermore preferred are the pyridine thioethers
Ia3.001-Ia3.116 of the formula Ia3, which differ from the compounds
Ia1.001-Ia1.116 in that a methylsulfonyl group is attached to the
pyridine ring in the 5-position. 7
TABLE 4
[0056] Furthermore preferred are the pyridine thioethers
Ia4.001-Ia4.116 of the formula Ia4, which differ from the compounds
Ia1.001-Ia1.116 in that a difluoromethyl group is attached to the
pyridine ring in the 5-position. 8
TABLE 5
[0057] Furthermore preferred are the thiopyridines Ib1.001-Ib1.116
of the formula Ib1, which differ from the compounds Ia1.001-Ia1.116
in that the corresponding sulfoxides are present. 9
TABLE 6
[0058] Furthermore preferred are the thiopyridines Ib2.001-Ib2.116
of the formula Ib2, which differ from the compounds Ia2.001-Ia2.116
in that the corresponding sulfoxides are present. 10
TABLE 7
[0059] Furthermore preferred are the thiopyridines Ib3.001-Ib3.116
of the formula Ib3, which differ from the compounds Ia3.001-Ia3.116
in that the corresponding sulfoxides are present. 11
TABLE 8
[0060] Furthermore preferred are the thiopyridines Ib4.001-Ib4.116
of the formula Ib4, which differ from the compounds Ia4.001-Ia4.116
in that the corresponding sulfones are present. 12
TABLE 9
[0061] Furthermore preferred are the thiopyridines Ic1.001-Ic.116
of the formula Ic1, which differ from the compounds Ia1.001-Ia1.116
in that the corresponding sulfones are present. 13
TABLE 10
[0062] Furthermore preferred are the thiopyridines Ic2.001-Ic2.116
of the formula Ic2, which differ from the compounds Ia2.001-Ia2.116
in that the corresponding sulfones are present. 14
TABLE 11
[0063] Furthermore preferred are the thiopyridines Ic3.001-Ic3.116
of the formula Ic3, which differ from the compounds Ia3.001-Ia3.116
in that the corresponding sulfones are present. 15
TABLE 12
[0064] Furthermore preferred are the thiopyridines Ic4.001-Ic4.116
of the formula Ic4, which differ from the compounds Ia4.001-Ia4.116
in that the corresponding sulfones are present. 16
[0065] Furthermore, processes have been found with which the
thiopyridines of the formula I can be prepared in surprisingly high
yields.
[0066] The thiopyridines I are especially preferably obtained when
substituted 3-chloro-2-halopyridines of the formula II 17
[0067] where R.sup.1 has the abovementioned meaning and Hal is
fluorine, chlorine or bromine are reacted, in a first step, with a
thio compound of the formula III
H[O].sub.mS(.dbd.O).sub.n--R.sup.2 III
[0068] where R.sup.2 has the abovementioned meaning and m and n are
0, or with an alkali metal or alkaline earth metal salt thereof, in
the presence or absence of a base, first to give a pyridine
thioether of the formula Ia and the latter is then oxidized
stepwise to the sulfoxide Ib 18
[0069] or sulfone Ic, or when the 3-chloro-2-halopyridines of the
formula II are directly reacted with a sulfinic acid of the formula
III, where R.sup.2 has the abovementioned meaning and m and n are
1, or with an alkali metal or alkaline earth metal salt thereof, in
the presence or absence of a base, to give the pyridylsulfones of
the formula Ic. A substance which is especially preferably employed
as compound II is 2,3-dichloro-5-trifluoromethylpyridine, which is
commercially available.
[0070] The synthesis of the compounds I is demonstrated by way of
example by the reaction described in the scheme below, which starts
with 2,3-dichloro-5-trifluoromethylpyridine and propylmercaptan
sodium salt as nucleophile, using hydrogen peroxide as the oxidant:
19
[0071] Instead of hydrogen peroxide, peracetic acid or chlorine and
bromine may also be used as the oxidant in a method similar to the
above equation.
[0072] In accordance with a further variant, the compounds I can be
prepared starting from 2,3-dichloro-5-trifluoromethylpyridine and a
benzenesulfinic acid salt as the nucleophile, as described in the
scheme below: 20
[0073] Preferred embodiments of the process are given
hereinbelow:
[0074] The reaction of the 3-chloro-2-halopyridines II with a thiol
III (m,n=0) or with a sulfinic acid III (m,n=1) is advantageously
carried out in the presence of a solvent from -20 to 200.degree.
C., preferably 10-180.degree. C., particularly preferably from 10
to 80.degree. C. for the thiol and from 80 to 180.degree. C. for
the sulfinic acid. Solvents which are used for these reactions
are--depending on the temperature range--hydrocarbons such as
pentane, hexane, cyclohexane, heptane, toluene, xylene, chlorinated
hydrocarbons such as methylene chloride, 1,2-dichloroethane,
1,1,2,2-tetrachloroethane, chlorobenzene, 1,2-, 1,3- or
1,4-dichlorobenzene, ethers such as diethyl ether, methyl
tert-butyl ether, tetrahydrofuran, 1,3- or 1,4-dioxane, anisole,
glycol ethers such as dimethyl glycol ether, diethyl glycol ether,
diethylene glycol dimethyl ether, esters such as ethyl acetate,
propyl acetate, methyl isobutyrate, isobutyl acetate, carboxamides
such as DMF, N-methylpyrrolidone, nitrohydrocarbons such as
nitromethane, nitroethane, nitropropane and nitrobenzene, ureas
such as tetraethylurea, tetrabutylurea, dimethylethyleneurea,
dimethylpropyleneurea, sulfoxides such as dimethyl sulfoxide,
sulfones such as dimethyl sulfone, diethyl sulfone, tetramethylene
sulfone, nitriles such as acetonitrile, propionitrile,
butyronitrile or isobutyronitrile; water, or else mixtures of these
up to a two-phase system. The process may also be carried out
according to the invention in the melt, without the addition of a
solvent.
[0075] The molar ratios at which the starting compounds are reacted
with each other are generally 0.9-1.4, preferably 0.95-1.1, for the
ratio of thiol, or sulfinic acid, to 3-chloro-2-halopyridine II.
The concentration of the starting materials in the solvent is 0.1-5
mol/l, preferably 0.2-2 mol/l.
[0076] The thiols, or sulfinic acids, are expediently employed in
the form of their alkali metal or alkaline earth metal salts, ie.
their lithium, sodium, potassium, magnesium or calcium salts.
However, the reaction can also be carried out in the presence of an
organic base, eg. triethylamine, tri-n-propylamine,
N-ethyldiisopropylamine, pyridine, .alpha.-, .beta.-,
.gamma.-picoline, 2,4-2,6-lutidine, N-methylpyrrolidine,
triethylenediamine, dimethylaniline, N,N-dimethylcyclohexylamine,
quinoline or acridine. In addition, it is also possible to bind the
hydrogen halide which is eliminated during the reaction by adding
an alkali metal hydride, alkali metal hydrogencarbonate, alkali
etal carbonate, alkaline earth metal hydride, alkaline earth etal
hydrogencarbonate or alkaline earth metal carbonate of the
abovementioned metals. The thiols, or sulfinic acids, are
advantageously converted into their corresponding salts using one
of the abovementioned bases in an inert solvent, to be followed by
he reaction with the 3-chloro-2-halopyridine. Depending on the
eactivity of the sulfur derivatives used, the water formed during
salt formation may be left in the reaction medium, or else removed
azeotropically with a solvent. Salt formation may also be carried
out in an aqueous phase to start with, whereupon the water is
removed. The salt formation may also be carried out with an alkali
metal hydride, alkali metal alkoxide, alkaline earth metal hydride
or alkaline earth metal alkoxide, preferably sodium methoxide or
sodium ethoxide, and the excess alcohol removed prior to the
reaction with the pyridine.
[0077] Finally, the reaction can also be carried out in an aqueous
two-phase system, preferably in the presence of phase-transfer
catalysts, such as quaternary ammonium or phosphonium salts. The
reaction conditions described in EP-A-556 737 are suitable for the
two-phase reaction.
[0078] It is advantageous to add the 3-chloro-2-halopyridine II to
a mixture of the thiol III or the sulfinic acid III or the
respective salt in one of the abovementioned solvents at from 10 to
80.degree. C. in the course of 0.25-2 hours and to stir for a
further 0.5 to 16 hours, preferably 2 to 8 hours, at from 10 to
80.degree. C. in the case of the thiol respectively at from 80 to
180.degree. C. in the case of the sulfinic acid so as to complete
the reaction.
[0079] However, it is also possible to add the thiol III or the
sulfinic acid III together or, via separate feeding, in parallel
with the addition of the base to the 3-chloro-2-halopyridine II and
then to finish the reaction as above.
[0080] When using an aqueous two-phase system, the starting
materials II and III can be added to a mixture of the
phase-transfer catalyst in the two phases in any sequence, with
stirring, and then the reaction can be finished in the
abovementioned temperature range with an addition of base.
[0081] The reaction can be carried out under atmospheric pressure
or superatmospheric pressure, continuously or batchwise.
[0082] The pyridine thioethers of the formula Ia can be oxidized to
the thiopyridines I preferably by means of hydrogen superoxide,
approximately equivalent amounts of oxidant giving the pyridine
sulfoxides Ib and approximately twice the molar amounts giving the
pyridine sulfones Ic.
[0083] Solvents which can be used are, for example, water,
acetonitrile, carboxylic acids such as acetic acid, trifluoroacetic
acid, propionic acid, alcohols such as methanol, ethanol,
isopropanol, tert-butanol, chlorinated hydrocarbons such as
methylene chloride, 1,1,2,2- tetrachloroethane or ketones such as
acetone or methyl ethyl ketone. Especially preferred are water,
methanol, acetic acid and trifluoroacetic acid.
[0084] In an especially preferred variant, the reaction can also be
catalyzed by adding stronger acids such as trifluoroacetic acid or
perchloric acid. However, metal compounds are also suitable as
catalysts, eg. transition metal oxides such as vanadium pentaoxide,
sodium tungstate, potassium dichromate, iron oxide tungstate,
sodium tungstate molybdic acid, osmic acid, titanium trichloride,
selenium dioxide, phenyleneselenic acid, oxovanadinyl
2,4-pentanedionate.
[0085] The catalysts are generally employed in an amount of from
0.5 to 10%, but it is also possible to employ stoichiometric
amounts due to the fact that the inorganic catalysts are readily
filtered off and recovered.
[0086] A further preferred oxidant is peracetic acid or hydrogen
superoxide/acetic anhydride, if appropriate also the peracetic acid
which exists in equilibrium with a hydrogen superoxide/acetic acid
mixture.
[0087] Another preferred oxidant is trifluoroperacetic acid, or the
mixture hydrogen superoxide/trifluoroacetic acid, or else the
mixture hydrogen peroxide/trifluoroacetic anhydride.
[0088] In general, oxidation with hydrogen superoxide in glacial
acetic acid is highly selective, but frequently slow. In general,
the reaction time can be shortened by adding trifluoroacetic acid
(cf. Synthesis Example 5, Variant a and b). The oxidation with
hydrogen peroxide in pure trifluoroacetic acid frequently leads to
the formation of the corresponding N-oxides, as described, inter
alia, in Chimia 29 (1975) 466. Rapid and selective oxidation of the
pyridine thioethers Ia to the corresponding sulfoxides Ib and
sulfones Ic is successfully carried out for example with solutions
of hydrogen superoxide in mixtures of acetic acid and
trifluoroacetic acid in a volumetric ratio of 10:1 to 1:1, in
particular 6:1 to 4:1. These mixtures are therefore especially
preferred as solvents.
[0089] Solvents which can furthermore be used are petroleum ether,
the abovementioned solvents, and the abovementioned catalysts.
[0090] In addition to peracetic acid and trifluoroperacetic acid,
it is also possible to employ perbenzoic acid, monoperphthalic acid
or 3-chloroperbenzoic acid, expediently in chlorinated hydrocarbons
such as methylene chloride or 1,2-dichloroethane.
[0091] Highly suitable for the oxidation of the thiols to
sulfoxides or sulfones are furthermore chlorine and bromine.
Advantageous solvents are water, acetonitrile, dioxane, two-phase
systems such as aqueous potassium hydrogen carbonate
solution/dichloromethane and, in the case of pyridine alkyl
thioethers, also acetic acid.
[0092] Other substances which can be employed as sources of active
halogen are tert-butyl hypochlorite, hypochlorous and hypobromous
acid, their salts, and furthermore N-halogen compounds such as
N-bromo- and N-chlorosuccinimide, or else sulfuryl chloride.
[0093] Other substances which are advantageous for the oxidation
are dinitrogen tetraoxide, eg. in the technologically simple
variant with air/nitrogen dioxide or nitrogen trioxide and, for
example, osmium(VIII) oxide as catalyst. In addition, the oxidation
can also be carried out directly with nitric acid, suitable
additional solvents being acetic anhydride, acetic acid, and
suitable catalysts being copper(I) bromide, copper(I) chloride,
copper(II) bromide and copper(II) chloride.
[0094] Also suitable for the oxidation is photo-sensitized oxygen
transfer, recommended photosensitizers being chlorophyll,
protoporphyrin, rose bengal or methylene blue. Suitable inert
solvents are hydrocarbons such as pentane, hexane, heptane,
cyclohexane, chlorinated hydrocarbons such as methylene chloride,
1,2-dichloroethane, 1,1,2,2-tetrachloroethane- , alcohols such as
methanol, ethanol, n-propanol or isopropanol, ketones such as
acetone, methyl ethyl ketone, polar aprotic solvents such as
acetonitrile, propionitrile or aromatic hydrocarbons such as
benzene, toluene, chlorobenzene or xylene. Instead of oxygen, it is
also possible to use ozone in the abovementioned solvents, and
additionally also ethers, 1,4-dioxane or THF.
[0095] In addition to photosensitization, it is also recommended to
use catalysts for the oxidation, for example oxides and sulfides of
nickel, copper, aluminum, tungsten, chromium, vanadium, ruthenium,
titanium, manganese, molybdenum, magnesium and iron.
[0096] Depending on the stoichiometry of the oxidants used, the
result is either the pyridine sulfoxides Ib or their pyridine
sulfones Ic. The molar ratios in which the starting compounds are
reacted with each other are generally 0.9-1.8, preferably 1.05-1.3
for the ratio of pyridine thioether Ia to oxidant in the case of
the oxidation to the pyridine sulfoxide, and generally 1.9-3.5,
preferably 2.05-2.9, in the case of the oxidation to the pyridine
sulfone.
[0097] The concentration of starting materials in the solvent is
generally 0.1-5 mol/l, preferably 0.2-2 mol/l.
[0098] It is advantageous to introduce the pyridine thioether or
the pyridine sulfoxide, if appropriate together with one of the
above-mentioned catalysts, into one of the abovementioned solvents
and then to add the oxidant in the course of 0.25-20 hours, with
stirring. The addition and reaction temperature depend on the
optimal efficacy of the oxidants in question and the avoidance of
secondary reactions. If photosensitized oxygen is used, the process
is generally carried out at from -20 to 80.degree. C., but if metal
catalysis is used, the process is generally carried out at from 50
to 140.degree. C., and when ozone is used generally at from -78 to
60.degree. C. Due to the limited solubility of the oxygen
derivatives, they have to be passed continuously into the reaction
mixture over a prolonged period (up to 20 hours) until oxidation on
the sulfoxide or sulfone level is complete. If air/nitrogen dioxide
or nitrogen trioxide is used, the process is preferably carried out
at from 15-150.degree. C. in the course of 1-15 hours. Liquid or
readily soluble oxidants such as hydrogen peroxide, peracetic acid,
or trifluoroperacetic acid, which is formed together with acetic
anhydride or in equilibrium with acetic acid and/or
trifluoroperacetic acid, respectively, or hypochlorous acid or
hypobromous acid, tert-butyl hypochlorite, chlorine or bromine,
N-chloro-, or N-bromosuccinimide or nitric acid can be added to the
reaction mixture of the pyridine thioether or pyridine sulfoxide
within shorter periods in the course of 0.25-6 hours, depending on
the exothermal character of the reaction, to complete the reaction
after a further 1-60 hours. Also preferred is a staggered addition
of the liquid or dissolved oxidant. In the case of hydrogen
superoxide and peracetic acid, or trifluoroperacetic acid, the
process is generally carried out at 0-90.degree. C., if tert-butyl
hypochlorite is used, generally at from -78 to 30.degree. C., if
N-halogen compounds are used, in general at 0-30.degree. C. and if
nitric acid is used in general at from 20 to 140.degree. C. In the
case of chlorine or bromine, a reaction temperature of 0-40.degree.
C. is recommended.
[0099] The oxidation reactions can be carried out under atmospheric
pressure or under elevated pressure, continuously or batchwise.
[0100] The thiopyridines I according to the invention are valuable
precursors for the preparation of crop protection agents, in
particular herbicides from the class of the phenylpyridines, as
they are described in WO-A 95/02580. 21
[0101] An especially advantageous process for the preparation of
herbicidal phenylpyridines based on the thiopyridines I according
to the invention is described in a parallel application, DE
Application No. 196 36995.9 (see Diagram 1). In addition, the
thiopyridines I can also be used as intermediates in organic
syntheses for the preparation of pharmaceuticals, colors and the
like.
SYNTHESIS EXAMPLES
Example 1
[0102] 3-Chloro-2-n-propylthio-5-trifluoromethylpyridine
[0103] 23.8 g (0.313 mol) of 1-propanethiol were added in the
course of 30 minutes to a mixture of 7.9 g (0.313 mol) of 95% pure
sodium hydride in 200 ml of THF while flushing with nitrogen and
stirring, a temperature of 25-30.degree. C. being maintained by
means of cooling. After the mixture had been stirred for 1 hour, 54
g (0.25 mol) of 2,3-dichloro-5-trifluorom- ethylpyridine in 50 ml
THF were added at 25-30.degree. C. in the course of 20 minutes with
stirring, and stirring was continued for 10 hours at 23.degree. C.
The reaction mixture was concentrated in vacuo, taken up in
methylene chloride, extracted with 0.5 N sodium hydroxide solution,
dried over magnesium sulfate and concentrated, yielding 63.5 g
(99.4%) of the title compound of n.sub.D.sup.23=1.5120.
Example 2
[0104] 3-Chloro-2-phenylthio-5-trifluoromethylpyridine
[0105] Variant a
[0106] Starting from 7.9 g (0.313 mol) of sodium hydride, 34.4 g
(0.313 mol) of thiophenol and 54 g (0.25 mol) of
2,3-dichloro-5-trifluoromethylp- yridine, 72.4 g (100% of theory)
of the title compound of n.sub.D.sup.24=1.5750 were obtained under
the conditions of Example 1.
[0107] Variant b
[0108] 108 g (0.981 mol) of thiophenol were added at 20-25.degree.
C. with stirring in the course of 1 hour to a mixture of 78.48 g
(0.981 mol) of 50% strength sodium hydroxide solution and 800 ml of
toluene. After the water had been removed under reflux conditions,
207.45 g (0.9316 mol) of 97% pure
2,3-dichloro-5-trifluoromethylpyridine were added at 80-50.degree.
C. in the course of 30 minutes with stirring to the suspension of
the above sodium thiophenolate, and stirring was continued for 1
hour at 50.degree. C. and 1 hour at 60.degree. C. The reaction
mixture was washed in succession with water, 0.5 N sodium hydroxide
solution and with water, dried over sodium sulfate and concentrated
in vacuo. This gave 276.2 g of the title compound of
n.sub.D.sup.24=1.5740 which, according to GC analysis, contained a
remainder of 2.9% of toluene;
[0109] Yield 268.2 g (99% of theory)
Example 3
[0110] 3-Chloro-2-n-propylsulfinyl-5-trifluoromethylpyridine
[0111] 8.4 g (0.124 mol) of 50% strength hydrogen peroxide were
added with stirring at 15-20.degree. C. in the course of 15 minutes
to a mixture of 31 g (0.1213 mol) of
3-chloro-2-n-propylthio-5-trifluoromethylpyridine in 150 ml of
acetic acid, during which process the temperature rose to
27.degree. C. in the course of 6 hours. After the reaction mixture
had been stirred for 14 hours at 25.degree. C., it was poured into
ice-water and extracted 3 times with methylene chloride. The
organic phase was washed with water and saturated sodium hydrogen
carbonate solution, dried and concentrated in vacuo, yielding 32 g
(97.2% of theory) of the title compound of m.p. 51-53.degree.
C.
Example 4
[0112] 3-Chloro-2-n-propylsulfonyl-5-trifluoromethylpyridine
[0113] 11.7 g (0.172 mol) of 50% strength hydrogen peroxide were
added at 20-25.degree. C. in the course of 30 minutes with stirring
to 20 g (0.0783 mol) of
3-chloro-2-n-propylthio-5-trifluoromethylpyridine in 150 ml of
glacial acetic acid, during which process the temperature climbed
up to 31.degree. C. in the course of 8 hours. After the reaction
mixture had been stirred for 60 hours, during which process it
cooled to 25.degree. C., it was poured into ice-water and worked up
as described. This gave 21 g (93.3% of theory) of the title
compound of m.p. 41-42.degree. C.
Example 5
[0114] 3-Chloro-2-phenylsulfinyl-5-trifluoromethylpyridine
[0115] Variant a
[0116] 6.2 g (0.09 mol) of 50% strength hydrogen superoxide were
added at 24.degree. C. in the course of 10 minutes with stirring to
a mixture of 22.5 g (0.077 mol) of
3-chloro-2-phenylthio-5-trifluoromethylpyridine in 150 ml of
glacial acetic acid, during which process the temperature climbed
up to 30.degree. C. in the course of 4 hours. The reaction mixture
was stirred for 14 hours at 30-25.degree. C., then poured into
ice-water and worked up as described. This gave 24.6 g of a viscous
oil which, according to HPLC check, contained 19.9 g (83.5% of
theory) of the title compound and 1.4 g (5.6% of theory) of the
corresponding sulfone. Chromatography with methylene chloride
through a suction filter with flash silica gel yielded the pure
title compound (18.2 g =76.6% of theory) of m.p. 79-80.degree.
C.
[0117] Variant b
[0118] 11.76 g (0.173 mol) of 50% strength hydrogen superoxide were
added at 25.degree. C. in the course of 20 minutes to a mixture of
50 g (0.173 mol) of 3-chloro-2-phenylthio-5-trifluoromethylpyridine
in 50 ml of trifluoroacetic acid and 250 ml of acetic acid. After
the reaction mixture has been stirred at 30 to 28.degree. C. for 4
hours, it was extracted with methylene chloride, and the organic
phase was washed with sodium hydrogen carbonate solution and with
water. Drying over magnesium sulfate and concentration in vacuo
yielded 48.5 g of colorless crystals of m.p. 67-68.degree. C.
According to NMR analysis, they contained 44.9 g (85% of theory) of
the pure title compound and 3.6 g (6.4% of theory) of the
corresponding sulfone.
Example 6
[0119] 3-Chloro-2-phenylsulfonyl-5-trifluoromethylpyridine
[0120] Variant a
[0121] 25.1 g (0.369 mol) of 50% strength hydrogen superoxide were
added at 35.degree. C. in the course of 30 minutes with stirring to
a mixture of 48.5 g (0.1675 mol) of
3-chloro-2-phenylthio-5-trifluoromethylpyridine in 300 ml of
glacial acetic acid and stirred for 18 hours at 40.degree. C. until
the exothermal reaction had subsided to 25.degree. C. After HPLC
check of the course of the reaction, a further 5 g (0.0735 mol) of
50% strength hydrogen superoxide were added and the mixture was
stirred for 2 hours at 40.degree. C. The reaction mixture was
poured into ice-water and worked up as described. This gave 49.2 g
of the title compound as a crude oil which, after chromatography
with methylene chloride through silica gel, solidified to give 44.5
g (82.6% of theory) of colorless crystals of m.p. 87-88.degree.
C.
[0122] Variant b
[0123] 273.2 g (0.495 mol) of 13.5% strength sodium hypochlorite
solution in 240 ml of water were added at 25-30.degree. C. in the
course of 2 hours to a mixture of 65.2 g (0.225 mol) of
3-chloro-2-phenylthio-5-trifl- uoromethylpyridine in 100 ml of
water and 100 ml of glacial acetic acid. After the mixture had been
stirred for 2 hours at 25.degree. C., a further 70 ml of glacial
acetic acid were added, and 84.5 g (0.153 mol) of 13.5% strength
sodium hypochlorite solution were fed in over 30 minutes. After the
reaction mixture had been stirred for 3 hours at 25.degree. C., it
was extracted with methylene chloride, and the organic extract was
washed with water, saturated sodium hydrogen carbonate solution and
again with water. The mixture was subsequently dried over magnesium
sulfate and concentrated in vacuo. This gave 70.9 g (98% of theory)
of the title compound of m.p. 91.degree. C. According to GC check,
the purity was 100%.
[0124] The protocols given in the above Synthesis Examples were
used for obtaining further pyridine thioethers Ia and thiopyridines
I by modifying the starting compounds as required. Selected
physical data of the pyridine thioethers are listed in Table 10 and
of the thiopyridines in Table 11.
2 TABLE 10 No. R.sup.1 R.sup.2 n.sub.D.sup.24 Fp [.degree. C.]
Ia2.003 CF.sub.3 n-C.sub.3H.sub.7 1.5120 Ia2.008 CF.sub.3
tert-C.sub.4H.sub.9 1.5069 Ia2.015 CF.sub.3 n-C.sub.6H.sub.13
1.5031 Ia2.029 CF.sub.3 n-C.sub.10H.sub.21 1.4930 Ia2.062 CF.sub.3
phenyl 1.5750 Ia2.065 CF.sub.3 4-chlorophenyl 63-65 Ia2.073
CF.sub.3 4-tolyl 1.5725 Ia2.080 CF.sub.3 4-methoxyphenyl 81-83
Ia2.105 CF.sub.3 benzyl 1.5645 Ic4.062 CF.sub.2H phenyl 50-53
Ic5.062 NO.sub.2 phenyl 103-104
[0125]
3 TABLE 11 No. R.sup.1 R.sup.2 n.sub.D.sup.24 Fp [.degree. C.]
Ib2.003 CF.sub.3 n-C.sub.3H.sub.7 51-53 Ib2.015 CF.sub.3
n-C.sub.6H.sub.13 1.5053 Ib2.062 CF.sub.3 phenyl 79-80 Ib2.065
CF.sub.3 4-chlorophenyl 124-125 Ib2.073 CF.sub.3 4-tolyl 73-75
Ib2.105 CF.sub.3 benzyl 102-103 Ic2.003 CF.sub.3 n-C.sub.3H.sub.7
41-42 Ic2.015 CF.sub.3 n-C.sub.6H.sub.13 1.4877 Ic2.062 CF.sub.3
phenyl 89-91 Ic2.065 CF.sub.3 4-chlorophenyl 105-108 Ic2.073
CF.sub.3 4-tolyl 65-68 Ic4.062 CF.sub.2H phenyl 69-72 Ic5.062
NO.sub.2 phenyl 158-159
Use Example
[0126] 3-Chloro-2-phenylsulfonyl-5-trifluoromethylpyridine was
stirred with 4-chloro-2-fluoro-5-methoxyphenylmagnesium bromide for
2.5 hours at room temperature in THF. Working-up by distillation
gave the coupling product
2-(4-chloro-2-fluoro-5-methoxyphenyl)-3-chloro-5-trifluoromethylp-
yridine in a yield of 84%, which is outstanding.
[0127] Further herbicidally active ingredients disclosed in WO
95/02580 are obtained in a simple manner by eliminating the methoxy
group in the 5-position on the benzene ring and other, prior-art
subsequent reactions.
* * * * *