Preparation of halogenated 4-aminophenols
View Patent ↗The present invention relates to halogenated 4-aminophenols and to halogenated 4-(phenyidiazenyl)phenols, to a process for their preparation and to the use of the halogenated 4-hydroxyphenols for preparing active ingredients, especially in pharmaceuticals and agrochemicals.
1. A process for preparing compounds of formula (VIII)
wherein
m is 0, 1, 2 or 3 and
n is 1, 2, 3 or 4,
where the sum of
m+n is a maximum of 4, and
R 1 is hydrogen, C 1 -C 12 -alkyl or C 5 -C 15 -arylalkyl and
R 2 is in each case independently C 1 -C 12 -fluoroalkyl, C 1 -C 12 -fluoroalkylthio or C 1 -C 12 -fluoroalkoxy;
Hal is in each case independently bromine, chlorine or fluorine; and
R 4 is 2,4-difluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl or 4-fluoro-3-chloro-phenyl
comprising:
(1) preparing compounds of formula (I)
wherein
m is 0, 1, 2 or 3 and
n is 1, 2, 3 or 4,
m+n is a maximum of 4, and
R 1 is hydrogen, C 1 -C 12 -alkyl or C 5 -C 15 -arylalkyl and
R 2 is in each case independently C 1 -C 12 -fluoroalkyl, C 1 -C 12 -fluoroalkylthio or C 1 -C 12 -fluoroalkoxy and
Hal is each case independently bromine, chlorine or fluorine, by
A1) converting a compound of the formula (II)
in which
is 0, 1, 2 or 3 and
R 3 is in each case independently fluorine, chlorine, bromine, iodine, cyano, thiocyanato, hydroxysulphonyl or alkali metal salts thereof, nitro, C 1 -C 12 -alkyl, C 1 -C 12 -fluoroalkyl, C 1 -C 12 -fluoroalkyoxy, C 1 -C 12 -fluoroalkylthio, C 1 -C 12 -alkoxy, C 1 -C 12 -alkoxycarbonyl, di(C 1 -C 12 -alkyl)amino, C 4 -C 14 -aryl or C 5 -C 15 -arylalkyl
to a diazonium salt of the formula (III)
in which An − is the anion of an acid and
A2) reacting
the diazonium salt of the formula (III) with compounds of the formula (IV)
in which
m, n, Hal and R 2 are each as defined under the formula (I)
in the presence of a base to give compounds of the formula (V)
and
B) converting, a compound of the formula (V) with a reducing agent to the compound of the formula (I), in which R 1 is hydrogen,
(2) converting at least one compound of formula (I) wherein R 1 is hydrogen, by O-alkylation to a compound of formula (I) in which R 1 is C 1 -C 12 -alkyl or C 5 -C 15 -arylalkyl, and
(3) converting at at least one compound of the formula (I) of step (2) by reacting with a compound of the formula (VIIa) or (VIIb)
wherein
R 4 is 2,4-difluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl or 4-fluoro-3-chlorophenyl and
R5 is optionally mono- or poly-chlorine- or -fluorine-substituted phenyl, to the compound of formula (VIII).
2. The process according to claim 1 , wherein the compound of formula (I) prepared is selected from the group consisting of 4-amino-2,3-difluorophenol, 4-amino-2,5-difluorophenol, 4-amino-2,6-difluorophenol, 4-amino-2-fluorophenol, 4-amino-3-chloro-5-fluorophenol, 4-amino-3-chloro-2-fluorophenol 4-amino-5-chloro-2-fluorophenol, 4-amino-3-bromo-5-fluorophenol, 4-amino-2-(trifluoromethoxy)phenol and 4-amino-3-(trifluoromethoxy)phenol, and combinations thereof.
3. The process according to claim 1 wherein the process further comprises converting a compound of the formula (VIII) by reacting with compounds of the formula (IX)
wherein
R 6 is C 1 -C 12 -alkyl, C 5 -C 15 -arylalkyl or C 4 -C 14 -aryl
to compounds of the formula (X)
wherein
m is 0, 1, 2 or 3 and
n is 1, 2, 3 or 4,
where the sum of
m+n is a maximum of 4, and
R 1 is hydrogen, C 1 -C 12 -alkyl or C 5 -C 15 -arylalkyl and
R 2 is in each case independently C 1 -C 12 -fluoroalkyl, C 1 -C 12 -fluoroalkylthio or C 1 -C 12 -fluoroalkoxy and
R 4 is 2,4-difluorophenyl, 4-fluorophenyl, 2,3-difluorophenyl or 4-fluoro-3-chlorophenyl, and
Hal is in each case independently bromine, chlorine or fluorine.