Process for producing substituted arylpyrazoles

Details Process for producing substituted arylpyrazoles Process for producing substituted arylpyrazoles

2001-07-26

2002-08-13

Ramsuer, Robert W. (Department: 1626)

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

Organic compounds

Nitriles

C568S308000

Reexamination Certificate

active

06433210

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
The invention relates to a novel process and novel intermediates for preparing substituted arylpyrazoles which are known as intermediates for herbicides.
BACKGROUND OF THE INVENTION
A number of processes for preparing herbicidally active arylpyrazoles have already been disclosed; however, these processes afford the desired products in not quite satisfactory yields (cf. U.S. Pat. No. 5,281,571).
DETAILED DESCRIPTION OF THE INVENTION
This invention, accordingly, provides a novel process for preparing substituted arylpyrazoles of the general formula (I)
in which
R
1
represents hydrogen or halogen,
R
2
represents cyano or halogen,
R
3
represents halogen, alkyl, halogenoalkyl or alkoxycarbonyl and
R
4
represents option ally substituted alkyl,
characterized in that in a first step halogenoarenes of the general formula (II)
in which
R
1
, R
2
and R
3
are each as defined above and
X represents halogen
are reacted with substituted alkines of the general formula (III)
in which
Z represents 1-hydroxy-isopropyl or trimethylsilyl,
if appropriate in the presence of one or more reaction auxiliaries and if appropriate in the presence of a diluent, at temperatures between 50° C. and 150° C., the substituted arylalkines formed of the general formula (IV)
in which
R
1
, R
2
, R
3
and Z are each as defined above are reacted
if appropriate without intermediate isolation
in a second step with an alkali metal hydroxide or alkaline earth metal hydroxide and/or an alkali metal fluoride or alkaline earth metal fluoride, if appropriate in the presence of a reaction auxiliary and if appropriate in the presence of a diluent, at temperatures between 50° C. and 150° C., the arylalkines formed of the general formula (V)
in which
R
1
, R
2
and R
3
are each as defined above
are reacted in a third step with acylating agents of the general formula (VI)
R
4
—CO—X
1
  (VI)
in which
R
4
is as defined above and
X
1
represents halogen or the group —O—CO—O—R
4
,
if appropriate in the presence of one or more reaction auxiliaries and if appropriate in the presence of a diluent, at temperatures between 0° C. and 150° C. and the arylalkinones formed of the general formula (VII)
in which
R
1
, R
2
R
3
and R
4
are each as defined above
are reacted in a fourth step with hydrazine (hydrate), if appropriate in the presence of a diluent, at temperatures between 0° C. and 150° C.
Surprisingly, the substituted arylpyrazoles of the general formula (I) can be obtained in very high yields and in very good quality by the process according to the invention.
The process according to the invention thus represents a useful advance on the prior art.
The process according to the invention preferably relates to the preparation of compounds of the formula (I) in which
R
1
represents hydrogen, fluorine or chlorine,
R
2
represents cyano, fluorine or chlorine,
R
3
represents halogen, C
1
-C
6
-alkyl, C
1
-C
6
-halogenoalkyl or C
1
-C
6
-alkoxy-carbonyl and
R
4
represents optionally fluorine- and/or chlorine-substituted C
1
-C
6
-alkyl.
The process according to the invention in particular relates to the preparation of compounds of the formula (I) in which
R
1
represents hydrogen, fluorine or chlorine,
R
2
represents cyano or chlorine,
R
3
represents fluorine, chlorine, methyl, ethyl, trifluoromethyl, methoxycarbonyl or ethoxycarbonyl and
R
4
represents methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, each of which is optionally substituted by fluorine and/or chlorine.
Using, for example, in the first step 4-bromo-3-fluoro-2-methyl-benzonitrile and 2-methyl-3-butin-2-ol as starting materials, reacting in the next stage with sodium hydroxide and then further with dichloroacetyl chloride and finally with hydrazine hydrate, the course of the reaction in the process according to the invention can be outlined by the following formula scheme:
The formula (II) provides a general definition of the halogenoarenes to be used as starting materials in the process according to the invention for preparing compounds of the formula (I). In the formula (II), R
1
, R
2
and R
3
each preferably or in particular have those meanings which have already been mentioned above, in connection with the description of the compounds of the formula (I) according to the invention, as being preferred or as being particularly preferred for R
1
, R
2
and R
3
; X preferably represents chlorine, bromine or iodine, in particular bromine or iodine.
The starting materials of the formula (II) are known and/or can be prepared by known processes (cf. J. Am. Chem. Soc. 81 (1959), 5643; J. Org. Chem. 27 (1962), 1426-1430; loc. cit. 59 (994), 7238-7242; J. Med. Chem. 13 (1970), 713-722).
The compounds of the formula (II) are obtained, for example, when
(a) benzene derivatives of the general formula (VIII)
in which
R
1
, R
2
and R
3
are each as defined above
are reacted with halogenating agents, such as, for example, chlorine, bromine or iodine, if appropriate in the presence of a catalyst, such as, for example, iron, at temperatures between 0° C. and 50° C. (cf. the Preparation Examples),
or when
(b) aniline derivatives of the general formula (IX)
in which
R
1
, R
2
and R
3
are each as defined above
are reacted with sodium nitrite in the presence of a hydrohalic acid, such as, for example, hydrochloric acid (hydrogen chloride), hydrobromic acid (hydrogen bromide) or hydroiodic acid (hydrogen iodide), if appropriate in the presence of a catalyst, such as, for example, copper(l) chloride, copper(I) bromide or copper(I) iodide, at temperatures between 0° C. and 50° C.
The substituted alkines further to be used as starting materials in the process according to the invention for preparing compounds of the formula (I) are known chemicals for synthesis.
The first step of the process according to the invention is carried out in the presence of one or more reaction auxiliaries.
These include palladium (if appropriate in the presence of a support material, such as, for example, activated carbon), palladium complexes, such as, for example, palladium-bis-(triphenylphosphine) dichloride [bis-(triphenylphosphine)-palladium(II) dichloride] or tetrakis-(triphenylphosphine)-palladium, and also palladium salts, such as, for example, palladium(II) acetate or palladium(II) chloride, if appropriate in the presence of triphenylphosphine and if appropriate in the presence of copper compounds, such as, for example, copper(I) chloride, copper(I) bromide or copper(I) iodide, and also—if appropriate as further reaction auxiliaries—basic organic nitrogen compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylamine, dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo[2,2,2]-octane (DABCO), 1,5-diazabicyclo[4,3,0]-non-5-ene (DBN), or 1 8 diazabicyclo[5,4,0]-undec-7-ene (DBU).
Suitable diluents for carrying out the process according to the invention are for all steps primarily inert organic solvents. These include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as acetone, butanone or methyl isobutyl ketone; nitriles, such as acetonitrile, propionitrile or butyrontrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; esters such as methyl acetate or ethyl acetate, and also sulphoxides, such as dimethyl sulphoxide.
When carrying out the first step of the

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