Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-05-17
2003-04-15
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06548677
ABSTRACT:
The present invention provides a process for preparing 2-alkyl-3-(4,5-dihydroisoxazol-3-yl)halobenzenes.
2-Alkyl-3-(4,5-dihydroisoxazol-3-yl)halobenzenes are starting materials for preparing 2-alkyl-3-(4,5-dihydroisoxazol-3-yl)acylbenzenes which can be used in the field of crop protection. Such compounds are described as herbicidally active compounds in WO 98/31681, for example.
It is an object of the present invention to provide an improved preparation process for 3-heterocyclyl-substituted benzoyl derivatives as described, for example, in WO 98/31681. The preparation process described in WO 98/31681 for the 2-alkyl-3-(4,5-dihydroisoxazol-3-yl)acylbenzenes and their precursors (2-alkyl-3-(4,5-dihydroisoxazol-3-yl)bromobenzenes) is not ideal for the large-scale industrial preparation of these compounds, since the synthesis involves a plurality of steps and the yield of the respective end product is relatively low, based on the starting materials employed in the first step of the synthesis.
We have found that this object is achieved by the process according to the invention, which permits the preparation of the 3-heterocyclyl-substituted benzoyl derivatives or their various precursors in good yield and on an advantageous economical scale. The process according to the invention has the advantage that the total yield of the end products in question, based on the starting materials used, is higher than the yield in the processes described in WO 98/31681. Furthermore, the starting materials can be prepared in a simple manner or can be purchased even in relatively large amounts, by a number of independent suppliers of raw materials, so that overall, a cheaper, economical and safe process for the large-scale industrial preparation of herbicidally active compounds is provided.
The present invention provides a process for preparing the compounds of the formula I
where:
n is 0,1 or 2;
R
1
, R
2
are C
1
-C
6
-alkyl;
R
3
, R
4
, R
5
are hydrogen or C
1
-C
6
-alkyl, in particular methyl, or R
4
and R
5
together form a bond;
R
6
is Cl, Br,
which comprises one or more of the following process steps a)-g):
a) halogenation of a 1,2-dialkylbenzene of the formula II
in which the radicals R
1
can be identical or different and are as defined above with halogens, in particular chlorine or bromine, to give the 3,6-dihalo-1,2-dialkylbenzenes of the formula III
b) reaction of a 3,6-dihalo-1,2-dialkylbenzene of the formula III with hydrogen peroxide and a halogenating agent, preferably HBr, to give the benzyl halides, in particular the benzyl bromides, of the formula IV
in which the radicals R
1
and R
6
are as defined above;
c) oxidation of the benzyl bromides of the formula IV with an oxidizing agent to give the aldehydes of the formula V
in which the substituents R
1
and R
6
are as defined above;
d) reaction of the compounds of the formula V with hydroxylamine and base to give the corresponding oximes of the formula VI
in which the substituents R
1
and R
6
are as defined above;
e) reaction of the oximes of the formula VI with an alkene of the formula VII
in which R
3
to R
5
are as defined in claim
1
, in the presence of a hypochlorite, to give the 4,5-dihydroisoxazole of the formula VIII
in which R
1
and R
3
to R
6
are as defined in claim 1;
f) reaction of the compound of the formula VIII with metal thiolates of the formula IX
R
2
−S
—
M
+
IX
in the presence of a solvent to give the thioethers of the formula X
in which R
1
to R
6
are as defined in claim 1;
g) if appropriate reaction of the thioethers of the formula X with an oxidizing agent to give the corresponding alkylsulfonyl or alkylsulfenyl derivatives of the formula I where n is the number 1 or 2.
In all cases, C
1
-C
6
-alkyl is a straight-chain or branched alkyl group having 1-6 carbons, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl or n-hexyl. This applies analogously to the C
1
-C
6
-alkoxy group.
R
4
and R
5
together may also represent a bond, resulting in the corresponding isoxazole derivatives. In this case, R
3
is preferably hydrogen.
The reaction sequence leading to the compounds of the formula I is compiled in the synoptical scheme below:
Hereinbelow, the individual steps are briefly illustrated in more detail.
1. Step a)
The halogenation is carried out by methods known from the literature, preferably using chlorine gas. Suitable solvents are alcohols, such as, for example, ethanol.
2. Step b)
The reaction is carried out under the following conditions: solvent: solvents which are inert to the bromination, such as: benzene, tert-butylbenzene, tert-amylbenzene, halogenated hydrocarbons, such as methylene chloride, chloroform, chlorobenzene 1,2-dichloroethane, carbon tetrachloride, dichlorobenzene or trichlorobenzene. Mixtures of these solvents may also be used. Brominating agent: bromine, bromine salts or HBr, preferably in an aqueous solution. Particular preference is given to using technical-grade azeotropic mixtures of HBr.
3. Step c)
NMMO: N-methylmorpholine N-oxide
Suitable for the oxidation are, for example, oxidizing agents, such as peracids, peroxides, hypochlorite, chlorine, sodium bromate and potassium peroxodisulfate; hydrogen peroxide is particularly suitable. It is known from the literature (DE-29 48 058) that alkyl halides and benzyl halides can be oxidized to the corresponding carbonyl compounds using amine oxides of tertiary amines or pyridine. The reaction is carried out under the following conditions: amine oxides: amine oxides having aliphatic, cycloaliphatic and aromatic radicals, such as trimethylamine, dimethylcyclopentylamine, dimethylamine. Furthermore amine oxides having cycloaliphatic radicals which are interrupted by heteroatoms (O; N). N-alkyl- and N-aryl-substituted piperidines, piperazines and morpholines.
Alternatively, it is possible to apply the method described in U.S. Pat. No. 2,902,515, where allyl halides are reacted with alkali metal nitronates to give the corresponding aldehydes. The conditions are, for example, the following: solvent: alcohols, such as methanol, ethanol, isopropanol, ethers, such as dioxane, THF, dipolar aprotic solvents, such as, for example, N,N-dialkylformamides, -acetamides, N-methylpyrrolidone, dimethylpropylene urea; tetramethyl urea, DMF, NMP, acetonitrile. Preference is given to methanol. The nitronates are generated as follows: reaction of lower nitroalkanes with alkali metal hydroxides (aqueous NaOH or KOH) or reaction of lower nitroalkanes with alkali metal alkoxides, such as KOtBu in butanol or sodium methoxide in methanol. The resulting nitronates are reacted with the benzyl halides. The reaction is carried out at temperatures from −10° C. to 80° C., preferably from 0° C. to 50° C. This is followed by aqueous work-up.
4. Step d)
The benzaldoxime can be obtained in virtually quantitative yield by standard processes starting from the corresponding aldehydes, by reaction with hydroxylamine in the presence of acid.
5. Step e)
The reaction of the benzaldoxime of the formula VI with alkenes of the formula VII to give compounds of the formula VIII proceeds via different intermediates. Since the first reaction step comprises the formation of an intermediate hydroxamic acid halide, a suitable oxidizing agent and a source of halogen or even the halogen itself have to be present. The second reaction step is the elimination of hydrogen halide giving the nitrile oxide, which reaction requires basic conditions. The final, third step is the cycloaddition of the nitrile oxide to the alkene.
This sequence can be carried out stepwise by customary processes using, for example, the free halogens bromine or chlorine for forming the hydroxamic acid halide. Since the hydroxamic acid halides have a tendency to decompose, they have to be converted quickly, using a base, into the even more sensitive nitrile oxides, which in most cases are trapped in situ with the alkene.
In the process according to the invention, these individual steps have now b
Baumann Ernst
Deyn Wolfgang von
Gebhardt Joachim
Götz Norbert
Hagen Helmut
BASF - Aktiengesellschaft
Higel Floyd D.
Keil & Weinkauf
Saeed Kamal
LandOfFree
Method of producing... 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 of producing..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of producing... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3106429