Process for preparing aryl-substituted pyrazoles
View Patent ↗The present invention relates to a process for preparing 1-aryl-substituted pyrazoles, comprising the reaction of alkoxy enones and enamino ketones with arylhydrazine derivatives to give 1-aryl-substituted dihydro-1H-pyrazoles, the further reaction thereof with elimination of water to give 1-aryl-substituted trihalomethylpyrazoles, and the further processing thereof.
1. A process for preparing an aryl-substituted pyrazole of general formula (I)
in which
R 1 is hydroxyl, alkoxy, aryloxy or halogen,
R 2 is hydroxyl, alkoxy, arylalkoxy, alkylthio, halogen, O—(C═O)alkyl, O—(C═O)O-alkyl, (C═O)haloalkyl, OSO 2 alkyl, OSO 2 -haloalkyl or OSO 2 -aryl,
R 3 is halogen, CN, NO 2 , alkyl, cycloalkyl, haloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkylamino, dialkylamino or cycloalkylamino,
Z is CH or N,
characterized in that
(A) an alkoxyenone or an enaminoketone of formula (II)
in which
R 4 is H, alkyl, arylalkyl, —(C═O)alkyl, (C═O)haloalkyl, —(C═O)O-alkyl, SO 2 alkyl, SO 2 -haloalkyl or SO 2 -aryl,
X is, chlorine, bromine or iodine,
R 5 is alkoxy, dialkylamino, cycloalkylamino or thioalkyl, or is cycloalkyl which may optionally contain 1-3 heteroatoms from the group of O, N or S,
is reacted with an arylhydrazine of the formula (III)
in which
R 3 is halogen, CN, NO 2 , alkyl, cycloalkyl, haloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkylamino, dialkylamino or cycloalkylamino,
Z is CH or N,
to give a 1-aryl-substituted dihydro-1H-pyrazole of the formula (IV)
in which X, R 3 , R 4 and Z are each as defined above,
(B) the latter is optionally converted further, without preceding isolation, with elimination of water, to a 1-aryl-substituted trihalomethylpyrazole of the formula (V)
in which X, R 3 , R 4 and Z are each as defined above,
(C) the compound of the general formula (V) is converted with addition of HC1, H 2 SO 4 or a base, to a pyrazolecarboxylic acid of the formula (VI)
in which R 3 , R 4 and Z are each as defined above,
(D) the latter is converted, after detaching the R 4 group, to a hydroxymethylpyrazole acid of the formula (VII)
in which R 3 and Z are as defined above, and
(E) the latter is converted to a compound of the formula (I)
2. The process according to claim 1 , characterized in that
R 1 is hydroxyl, (C 1 -C 6 )-alkoxy or halogen,
R 2 is hydroxyl, halogen or O—(C═O)(C 1 -C 6 )alkyl,
R 3 is halogen, CN, NO 2 , (C 1 -C 6 )-alkyl, halo(C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy or halo(C 1 -C 6 )alkoxy,
X is chlorine or bromine,
Z is N,
R 4 is aryl(C 1 -C 6 )-alkyl, (C═O)(C 1 -C 6 )-alkyl, (C═O )halo(C 1 -C 6 )-alkyl, —(C═O)O—(C 1 -C 6 )-alkyl, SO 2 (C 1 -C 6 )-alkyl, SO 2 phenyl or —SO 2 -halo(C 1 -C 6 )-alkyl,
R 5 is (C 1 -C 6 )-alkoxy, di(C 1 -C 6 )-alkylamino, morpholino or thioalkyl.
3. The process according to claims 1 or 2 , characterized in that
R 1 is (C 1 -C 6 )alkoxy or hydroxyl,
R 2 is hydroxyl or C(═O)CH 3 ,
R 3 is chlorine,
R 4 is (C═O)CH 3 ,
R 5 is methoxy,
X is chlorine,
Z is N.
4. The method according to claim 1 wherein X is chlorine.
5. The method according to claim 2 wherein X is chlorine.
6. The process of claim 1 , wherein R 1 is alkoxy.
7. The process of claim 1 , wherein R 1 is hydroxyl.
8. The process of claim 1 , wherein R 1 is aryloxy.
9. The process of claim 1 , wherein R 1 is halogen.
10. The process of claim 1 , wherein Z is N.
11. The process of claim 1 , wherein Z is CH.
12. The process of claim 1 , wherein R 3 is chlorine.
13. The process of claim 1 , wherein R 2 is hydroxyl.
14. The process of claim 1 , wherein R 2 is O(C ═O)CH 3 .
15. The process of claim 1 , wherein R 2 is halogen.
16. The process of claim 1 , wherein the alkoxyenone or enaminoketone of formula (II) is reacted with the arylhydrazine of formula (III) at a temperature ranging from -20 ° C. to 25 ° C.