Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-11-02
2003-02-25
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06525204
ABSTRACT:
The present invention provides a process for preparing isoxazolin-3-ylacylbenzenes, novel intermediates and novel processes for preparing these intermediates.
Isoxazolin-3-ylacylbenzenes are useful compounds which can be used in the field of crop protection. WO 98/31681, for example, describes 2-alkyl-3-(4,5-dihydroisoxazol-3-yl)acylbenzenes as herbicidally active compounds.
It is an object of the present invention to provide an alternative process for preparing 3-heterocyclyl-substituted benzoyl derivatives. The preparation process described in WO 98/31681 for 2-alkyl-3-(4,5-dihydroisoxazol-3-yl)acylbenzenes or precursors thereof (2-alkyl-3-(4,5-dihydroisoxazol-3-yl)bromobenzene derivatives) is not particularly suitable for the industrial preparation of these compounds, since the synthesis involves a plurality of steps and the yield of the end product in question, based on the starting materials employed in the first step of the synthesis, is relatively low.
The preparation of compounds or intermediates with a structure similar to that of the compounds of the formula I is known from the literature:
WO 96/26206 discloses a process for preparing 4-[3-(4,5-dihydroisoxazol-3-yl)benzoyl]-5-hydroxypyrazoles where, in the last step, a 5-hydroxypyrazole is reacted with a 3-(4,5-dihydroisoxazol-3-yl)benzoic acid derivative. The 3-(4,5-dihydroisoxazol-3-yl)benzoic acid derivative required for this process can only be obtained with difficulty, via a large number of steps. Accordingly, the process is relatively expensive and not optimal economically.
DE 197 09 118 describes a process for preparing 3-(4,5-dihydroisoxazol-3-yl)benzoic acids starting from 3-bromo-(4,5-dihydroisoxazol-3-yl)benzene, Grignard reagents and carbon dioxide.
Surprisingly, we have found that the number of process steps in the preparation of the 3-heterocyclyl-substituted benzoyl derivatives can be reduced compared to the process described in WO 98/31681 if the synthesis is carried out via selected intermediates. Moreover, the process according to the invention has the advantage that the overall yield of the end products of the formula I and also that of the intermediates X, based on the starting materials employed, is higher than the yield of the processes described in WO 98/31681. Furthermore, the respective intermediates of the individual process steps can be obtained in good yield. Moreover, some of the individual process steps are advantageous for the industrial preparation of the intermediates, since they allow a cost-effective and economic preparation of the latter. Furthermore, it is advantageous that the starting materials used are basic chemicals which are easy to prepare and which can be obtained from several independent suppliers of raw materials, even in relatively large amounts. Overall, the process according to the invention provides a more cost-effective, economical and safe industrial process for preparing herbicidally active compounds of the formula I.
We have found that the object of the invention is achieved by a process for preparing compounds of the formula I
where the substituents are as defined below:
R
1
is hydrogen, C
1
-C
6
-alkyl,
R
2
is C
1
-C
6
-alkyl,
R
3
, R
4
, R
5
are hydrogen, C
1
-C
6
-alkyl, or R
4
and R
5
together form a bond,
R
6
is a heterocyclic ring,
n is 0, 1 or 2;
which comprises preparing an intermediate of the formula VI
in which R
1
and R
3
-R
5
are as defined above.
In subsequent reaction steps, compounds of the formula VI are converted into the corresponding 3-bromo-substituted compounds (bromobenzene derivatives), and the amino group on the phenyl ring is transformed into a sulfonyl group, giving compounds of the formula X:
The compounds of the formula X (3-(4,5-dihydroisoxazol-3-yl)bromobenzenes) are useful intermediates for preparing active compounds of the formula I. In particular, the process according to the invention affords the compounds I in the last reaction step in good yield. The compounds I are suitable, for example, for use as crop protection agents, in particular as herbicides, as described in WO 96/26206 and WO 97/35850.
According to the invention, the compounds of the formula I and the required intermediates, in particular compounds of the formula VI or X, can be prepared advantageously by combining one or more of the following process steps a)-g):
a) reaction of a nitro-o-methylphenyl compound of the formula II
in which the radical R
1
is as defined above with an organic nitrite R—ONO in the presence of a base to give an oxime of the formula III
in which the radical R
1
is as defined above;
b) cyclization of the oxime of the formula III with an alkene of the formula IV
in which R
3
to R
5
are as defined in claim 1 in the presence of a base to give the isoxazole of the formula V
in which R
1
and R
3
to R
5
are as defined in claim 1;
c) reduction of the nitro group in the presence of a catalyst to give the aniline of the formula VI
in which R
1
and R
3
to R
5
are as defined in claim 1;
d) reaction of the aniline of the formula VI with a dialkyl disulfide of the formula VII
R
2
—S—S—R
2
VII
in the presence of an organic nitrite R—ONO and, if appropriate, a catalyst to give the thioether of the formula VIII
in which R
1
to R
5
are as defined in claim 1;
e) bromination of the thioether of the formula VIII with a brominating agent to give the bromothioether of the formula IX
in which R
1
to R
5
are as defined in claim 1;
f) oxidation of the bromothioether of the formula IX with an oxidizing agent to give the isoxazoles of the formula X
where n is the numbers 1 or 2,
g) if appropriate reacting the isoxazoline of the formula X with a compound of the formula R
6
—OH (XI) in the presence of carbon monoxide, a catalyst and a base, to give the compounds of the formula I.
Essentially, the process according to the invention for preparing compounds X comprises one or more of the process steps a)-f) or, in the case of the compounds I, one or more of the process steps a)-g). Preference is given to those reaction sequences which comprise either one of the process steps a) or d) or else both steps a) and d).
C
1
-C
6
-Alkyl and C
1
-C
4
-alkyl are straight-chain or branched alkyl groups having 1-6 and 1-4 carbon atoms, respectively, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl or n-hexyl in all cases. This applies analogously to the C
1
-C
6
-alkoxy group.
R
1
is preferably an alkyl group, in particular methyl, ethyl, isopropyl, n-propyl or n-butyl group [sic].
R
3
, R
4
and R
5
are preferably hydrogen. R
4
and R
5
together may also denote a bond, giving rise to the corresponding isoxazole derivatives. In this case, R
3
is preferably hydrogen.
In the definition of R
6
, “heterocyclic ring” means a saturated, unsaturated or partially unsaturated heterocycle having one, two or three oxygen, sulfur or nitrogen atoms. Preference is given to heterocycles having two nitrogen atoms. In particular, R
6
is a pyrazole radical, as described in more detail in WO 98/31681. It is preferably a pyrazole which is attached in the 4-position and which may be unsubstituted or substituted by further radicals which are chemically inert under the chosen reaction conditions. Suitable pyrazole substituents of this type are, for example, the following groups: hydroxyl, oxo, sulfonyloxy, C
1
-C
6
-alkyl or C
1
-C
6
-alkoxy, in particular C
1
-C
4
-alkyl in the 1-position. Particularly preferably, R
6
is the group 1-alkyl-5-hydroxypyrazol-4-yl, in particular 1-methyl-5-hydroxypyrazol-4-yl; 1-ethyl-5-hydroxypyrazol-4-yl.
The process according to the invention is particularly suitable for preparing the following compounds of the formula I:
1-methyl-4-(3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl)-5-hydroxypyrazole,
1-ethyl-4-(3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl)-5-hydroxypyrazole,
1-methyl-4-(3-(4,5-dihydroisoxazol-3-yl)-2-ethyl-4-methylsulfonylbenzoyl)-5-hydroxypyrazole,
1-methyl-4-(3-(4,5-dihydroisoxazol-3-yl)-2-propyl-4-methylsulfonyl
Baumann Ernst
Deyn Wolfgang von
Gebhardt Joachim
Götz Norbert
Hagen Helmut
McKane Joseph K.
Wright Sonya
LandOfFree
Method for producing isoxazoline-3-yl-acyl benzene does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for producing isoxazoline-3-yl-acyl benzene, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing isoxazoline-3-yl-acyl benzene will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3182919