Processes for preparing intermediates

Details Processes for preparing intermediates Processes for preparing intermediates

2000-12-04

2003-11-04

Barts, Samuel (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C568S319000, C568S329000, C568S338000, C568S343000, C568S346000, C560S055000, C560S118000, C560S124000

Reexamination Certificate

active

06642418

ABSTRACT:

This invention relates to novel processes for preparing intermediates (particularly beta keto ester and 1,3-dione compounds) useful in the manufacture of pesticides.
Pesticidal 4-benzoylisoxazoles, particularly 5-cyclopropylisoxazole herbicides and intermediate-compounds in their synthesis, are described in the literature, for example in European Patent Publication Nos. 0418175, 0487353, 0527036, 0560482, 0609798 and 0682659.
Various methods for preparing these compounds are known. The present invention seeks to provide improved or more economical methods for the preparation of pesticides and the intermediate compounds useful in preparing them. The present invention accordingly provides a process (A) for the preparation of a compound of formula (I):
wherein:
one of the groups R
1
and R
2
is cyclopropyl and the other is phenyl substituted by two or three groups, which may be the same or different, selected from halogen, nitro, cyano, —(CR
4
R
5
)S(O)
p
R
6
, —S(O)
p
R
6
, C
1-6
alkoxy, C
1-4
haloalkoxy, C
1-4
alkyl, C
1-4
haloalkyl, 1,2,4-triazol-1-yl and —SF
5
; wherein:
p is zero, one or two;
R
4
and R
5
are independently hydrogen or C
1-4
alkyl; and
R
6
is C
1-4
alkyl; which process comprises the hydrolysis and decarboxylation of a compound of formula (II):
wherein R
1
and R
2
are as hereinbefore defined and R
3
is C
1-4
alkyl.
Certain compounds of formula (I) are known and a number of processes for their preparation and conversion into herbicidal 4-benzoylisoxazole derivatives have been described in the European Patent Applications cited above.
In formulae (I) and (II) and in the formulae depicted hereinafter, preferred values of the symbols are as follows:
Preferably the group R
1
or R
2
which is substituted phenyl is substituted by two or three groups selected from halogen, trifluoromethyl, nitro, —CH
2
S(O)
p
CH
3
, —S(O)
p
CH
3
, methoxy, methyl and 1,2,4-triazol-1-yl.
More preferably the group R
1
or R
2
which is substituted phenyl has as one of the substituents a 2-S(O)
p
CH
3
group.
More preferably the group R
1
or R
2
which is substituted phenyl is selected from:
2-S(O)
p
CH
3
-4-CF
3
; 2-S(O)
p
CH
3
-3-OCH
3
-4-F; 2-CH
2
S(O)
p
CH
3
-4-Br; 2-(1,2,4-triazol-1-yl)-4-CF
3
; and 2-NO
2
-4-S(O)
p
CH
3
substituted phenyl.
Most preferably the group R
1
or R
2
which is substituted phenyl is selected from:
2-S(O)
p
CH
3
-4-CF
3
; and 2-S(O)
p
CH
3
-3-OCH
3
-4-F substituted phenyl.
Preferably R
3
is methyl or ethyl.
The preparation of compounds of formula (I) from compounds of formula (II) may be effected in a polar or a non-polar solvent (polar solvents are preferred). Preferably the solvent is water miscible. Examples of polar solvents include nitriles, particularly acetonitrile; dimethyl sulphoxide; dimethyl formamide; N,N-dimethylacetamide; N-methyl pyrrolidone; and ethers particularly dioxane and tetrahydrofuran. Acetonitrile is a preferred solvent for process (A). Examples of non-polar solvents include aromatic or aliphatic hydrocarbons, for example toluene and xylenes; or aromatic or aliphatic halogenated hydrocarbons, for example chlorobenzenes. The presence of water in the solvent medium is generally required. The amount of water may vary from catalytic to a large excess and it may be used as a co-solvent. The ratio of solvent/water is preferably from about 99.9:0.1 to about 9:1 (by volume).
Generally the reaction temperature used is from 0° C. to the boiling point of the solvent, preferably from 20° C. to 120° C., and more preferably from 60° C. to 100° C.
Generally the reaction takes place in the presence of a strong acid, usually a mineral acid, for example sulphuric acid or preferably hydrochloric acid, or an organic carboxylic acid such as trifluoroacetic acid. The amount of acid which is present can vary from a catalytic quantity to a large excess. Generally a catalytic amount gives good results.
By performing the reaction using acidic conditions and readily available reagents, the compounds of formula (I) may be obtained conveniently and in high yield with minimal formation of by products. The reaction is particularly useful for lower alkyl esters of formula (II), especially those where R
3
represents methyl or ethyl, because these compounds may be prepared from more readily available or less expensive starting materials.
According to a further feature of the present invention there is provided a process (B) for the preparation of a compound of formula (II) which comprises the acylation of a compound of formula (III):
wherein R
1
and R
3
are as hereinbefore defined, with a compound of formula (IV):
R
2
C(═O)X  (IV)
wherein R
2
is as hereinbefore defined, and X is a leaving group, generally a halogen atom (preferably chlorine); or an imidazol-1-yl group.
In formulae (III) and (IV) the above preferred values for R
1
and R
2
are as hereinbefore defined for formulae (I) and (II).
In a particularly preferred aspect of the process (B), the group R
1
represents cyclopropyl; R
2
represents 2-S(O)
p
CH
3
-4-CF
3
or 2-S(O)
p
CH
3
-3-OCH
3
-4-F substituted phenyl; and R
3
represents methyl, ethyl or tert butyl.
Compounds of formula R
2
C(═O)X and their carboxylic acid precursors are generally known in the literature when R
2
is cyclopropyl, and when R
2
is substituted phenyl their preparation is generally described in the European Patent Applications cited above and related publications.
The preparation of compounds of formula (II) from compounds of formula (III) and (IV) may be effected (a) by reacting a metal enolate of the compound of formula (III) with an acylating agent (IV). The metal enolate is preferably a magnesium enolate and is prepared, generally in situ, by reaction of (III) with a magnesium alkoxide base preferably magnesium methoxide or ethoxide. When a magnesium alkoxide is used it is generally employed in an equimolar amount.
The reaction of compounds of formula (III) and (IV) may also be effected (b) in the presence of a magnesium halide and a base. The magnesium halide is generally magnesium chloride, bromide or iodide, (magnesium iodide being conveniently prepared in situ using magnesium chloride and an alkali metal iodide, preferably sodium iodide or potassium iodide). The base used may be selected from trialkylamines, such as triethylamine, and pyridine. The amount of magnesium halide used is generally 1 equivalent, and the amount of base used is generally from 1 to 2 equivalents, preferably 2 equivalents. The reaction temperature is generally from 0° C. to 100° C., preferably from 0° C. to 30° C.
When the above reaction is performed using a magnesium enolate a side reaction may occur in which the compound (IV) reacts with alkoxide which is present as part of the magnesium enolate complex (even after removal of all of the alkanol that may have been present when used as solvent), resulting in the alkanoyl ester of (IV). Although this is not usually a problem, depending upon the particular compound (IV) used, the side reaction can become important and lead to a reduced yield of (II). This problem is substantially avoided when the magnesium halide/base procedure referred to above is adopted.
Solvents suitable for the above process for the preparation of compounds of formula (II) include nitrites, preferably acetonitrile; aromatic hydrocarbons preferably toluene; chlorinated hydrocarbons, such as dichloromethane; chlorinated aromatic solvents such as chlorobenzene; and ethers such as tetrahydrofuran and 1,4-dioxan.
Compounds of formula (II) wherein R
3
represents C
1-3
alkyl are novel and as such constitute a further feature of the present invention.
According to a further feature of the present invention there is provided a process (C) for the preparation of a compound of formula (III) by the reaction of a compound of formula (V):
wherein R
1
is as hereinbefore defined, and Y represents a leaving group, for example cyano or preferably an optionally substituted imidazol-1-yl ring; with a compound of formula (VI):
wherein R
3
is as hereinbefore defined; to obtain, via the decarboxylation of an

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