Method for producing chlorobenzoxazolene

Details Method for producing chlorobenzoxazolene Method for producing chlorobenzoxazolene

2000-06-14

2001-08-14

Lambkin, Deborah C. (Department: 1626)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

06274739

ABSTRACT:

The invention relates to the technical field of the processes for preparing intermediates which can be employed for syntheses of active compounds, for example active compounds for crop protection agents or pharmaceuticals.
Chlorobenzoxazoles have already attained great importance as intermediates for crop protection agents and pharmaceuticals. Their properties and processes for their preparation are described, inter alia, in DE-A-3207153; EP-A-43573 and GB-A-913910.
Using processes from the abovementioned publications, chlorobenzoxazoles can be prepared, for example, from 2-mercapto-1,3-benzoxazoles by exchanging the mercapto group with chlorine using various chlorinating agents. Sulfur chlorides requiring disposal are obtained as byproducts.
A further preparation method involves appropriately substituted 1,3-benzoxazol-2-ones which are converted into chlorobenzoxazoles using an excess of phosphorus pentachloride (EP-A-572893; EP-A-141053; DE-A-3406909). In the case of the preparation of 2,6-dichlorobenzoxazole, for example, 6-chlorobenzoxazol-2-one is employed. The reprocessing of the excess of PCl
5
employed in this process requires a special effort.
It is already known that the unsubstituted thioanalog 1,3-benzothiazole compound can be converted into 2-chlorobenzo-1,3-thiazole by direct chlorination in the presence of chlorination catalysts (DE-A-3234530). However, this selective monochlorination reaction is not known for the analogous benzoxazole; on the contrary, DE-A-2059725 shows that in this case perchlorination occurs in the molecule, without any selectivity in the occupation of the possible substitution sites.
An alternative process for preparing chlorobenzoxazoles is required which does not have the disadvantages of the abovementioned processes. Surprisingly, it has now been found that chlorobenzoxazoles can be obtained from benzoxazoles by direct chlorination. Both monochlorinations and, alternatively, certain dichlorinations can be carried out in this process.
The invention accordingly provides a process for preparing chlorobenzoxazoles of the formula (I),
in which R
1
, R
2
and R
4
are each, independently of one another, H, halogen, CN, NO
2
, C
1
-C
5
-alkyl, C
1
-C
5
-alkoxy, aryl or aryloxy, where each of the 4 lastmentioned radicals is unsubstituted or substituted, and
(Case a) R
3
=H, halogen, CN, NO
2
, C
1
-C
5
-alkyl, C
1
-C
5
-alkoxy, aryl or aryloxy, where each of the 4 lastmentioned radicals is unsubstituted or substituted, or
(Case b) R
3
=chlorine,
which comprises reacting benzoxazoles of the formula (II),
 in which R
1
, R
2
and R
4
are as defined in formula (I) and R
3
in case (a) is as defined in formula (I) and R
3
in case (b) is hydrogen,
in the presence of an acidic catalyst with a chlorinating agent to give the monochlorination product (I) or in case (b) with an excess of the chlorinating agent to give the dichlorination product (I) in which R
3
=chlorine.
According to the invention, the 2-chloroderivatives of the formula (I) can be prepared selectively in high yield and purity. Moreover, our experiments show that, if the chlorination reaction of benzoxazoles, preferably of unsubstituted benzoxazole, to the corresponding 2-chlorobenzoxazole is continued using excess chlorinating agent, 2,6-dichlorinated benzoxazoles, preferably 2,6-dichlorobenzoxazole, can be obtained selectively. Such a selectivity was unforeseeable.
Owing to the results described in DE-A-2059725 the chlorination of benzoxazole was expected to result in unselective polychlorination. Furthermore, it was not expected that the conditions described for the chlorination of benzothiazole to give 2-chlorobenzothiazole (DE-A-3234530) could be transferred to the benzoxazole molecule, since the benzoxazole skeleton and in particular benzoxazole itself is known to be a much more sensitive (reactive) molecule system and molecule, respectively. It was therefore possible to explain the technical teachings from DE-A-2059725 and DE-A-3234530 without any contradiction. Surprisingly, however, it is possible to carry out selective chlorinations under the conditions according to the invention even with benzoxazoles, and the chloroderivatives of the formula (I) are usually obtained in high yield and selectivity.
Of particular interest are processes according to the invention for preparing chlorobenzoxazoles of the abovementioned formula (I),
in which R
1
, R
2
and R
4
are each, independently of one another, H, halogen, CN, NO
2
, C
1
-C
5
-alkyl, C
1
-C
5
-haloalkyl, C
1
-C
5
-alkoxy, C
1
-C
5
-haloalkoxy, phenyl or phenoxy, where each of the 2 lastmentioned radicals is unsubstituted or substituted by one or more radicals selected from the group consisting of halogen, CN, NO
2
, C
1
-C
4
-alkyl, C
1
-C
4
-haloalkyl, C
1
-C
4
-alkoxy and C
1
-C
4
-haloalkoxy,
preferably H, halogen, such as fluorine, chlorine, bromine or iodine, methyl, ethyl, methoxy, ethoxy, CF
3
, CCl
3
, OCF
3
or OCHF
2
, in particular H or chlorine, and
(Case a) R
3
in formula (I) is a radical selected from the group of the radicals possible for R
1
, R
2
and R
4
, preferably H or chlorine, or
(Case b) R
3
in formula (I) is chlorine.
In the formulae (I) and (II), the radicals alkyl, alkoxy, haloalkyl, haloalkoxy, and also the corresponding unsaturated and/or substituted radicals, can in each case be straight-chain or branched in the carbon skeleton. Unless specifically defined, the lower carbon skeletons, for example those having 1 to 4 carbon atoms and 2 to 4 carbon atoms in the case of unsaturated groups, are preferred for these radicals. Alkyl radicals, also in composite meanings, such as alkoxy, haloalkyl and the like, are, for example, methyl, ethyl, n- or i-propyl, n-, i-, t- or 2-butyl, pentyls, hexyls, such as n-hexyl, i-hexyl and 1,3-dimethylbutyl, heptyls, such as n-heptyls, 1-methylhexyl and 1,4-dimethylpentyl.
Halogen is, for example, fluorine, chlorine, bromine or iodine, haloalkyl, -alkenyl and -alkynyl are alkyl, alkenyl and alkynyl, respectively, which are partially or fully substituted by halogen, preferably by fluorine, chlorine and/or bromine, in particular by fluorine or chlorine, for example CF
3
, CHF
2
, CH
2
F, CF
3
CF
2
, CH
2
FCHCl
2
, CCl
3
, CHCl
2
, CH
2
CH
2
Cl; haloalkoxy is, for example, OCF
3
, OCHF
2
, OCH
2
F, CF
3
CF
2
O, OCH
2
CF
3
and OCH
2
CH
2
Cl; this applies correspondingly to haloalkenyl and other halogen-substituted radicals.
Aryl is a monocyclic, carbocyclic aromatic ring which, in the substituted case, also includes a bi- or polycyclic aromatic system, which contains at least one aromatic ring and optionally further aromatic rings or partially unsaturated or saturated rings; aryl is, for example, phenyl, naphthyl, tetrahydronaphthyl, indenyl, indanyl, pentalenyl, fluorenyl and the like, preferably phenyl. Aryloxy is preferably an oxy radical which corresponds to the abovementioned aryl radical, in particular phenoxy.
Substituted radicals, such as substituted alkyl, aryl, phenyl or phenoxy, are, for example, substituted radicals which are derived from the unsubstituted parent compound, the substituents being, for example, one or more, preferably 1, 2 or 3, radicals selected from the group consisting of halogen, alkoxy, haloalkoxy, alkylthio, hydroxyl, amino, nitro, cyano, azido, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, substituted amino, such as acylamino, mono- or dialkylamino, and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkyl sulfonyl and, in the case of cyclic radicals, also alkyl and haloalkyl. Preferred radicals having carbon atoms are those having 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms. Preference is usually given to substituents selected from the group consisting of halogen, for example fluorine and chlorine, C
1
-C
4
-alkyl, preferably methyl or ethyl, C
1
-C
4
-haloalkyl, preferably trifluoromethyl, C
1
-C
4
-alkoxy, preferably methoxy or ethoxy, C
1
-C
4
-haloalkoxy, nitro and cyano. Particular preference here is given to the substituents methyl, methoxy and chl

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