Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2002-04-05
2004-07-06
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
Reexamination Certificate
active
06759558
ABSTRACT:
BACKGROUND
The present invention relates to a process for preparing halogen-substituted dibenzyl alcohols from the corresponding halogen-substituted terephthalic acids, to the halogen-substituted dibenzyl alcohols obtainable by this process and to their use for preparing pharmaceutically and agrochemically active compounds.
2,3,5,6-Tetrahalodibenzyl alcohols are known to the person skilled in the art as important intermediates, for example for preparing pharmaceutically or agrochemically active compounds such as insecticides. 2,3,5,6-Tetrafluorodibenzyl alcohol, in particular, is an important intermediate in the preparation of insecticidally active pyrethroids.
The use of 2,3,5,6-tetrafluorodibenzyl alcohol as a starting material in the preparation of household insecticides is described, for example, in EP-A-0 963 976, EP-A-0 959 065, EP-A-0 302 612 and EP-A-0 926 129.
The preparation of 2,3,5,6-tetrafluorodibenzyl alcohol by borohydride reduction from derivatives of tetrafluoroterephthalic acid is described in GB-A-2,127,013. Here, the reduction of tetrafluoroterephthalic acid chloride is carried out using sodium borohydride in diglyme at a temperature of 20° C. giving the tetrafluorodibenzyl alcohol in a yield of only 64.4%. Nothing is said about the purity.
Furthermore, WO-A-00/68173 describes the synthesis of tetrafluorodibenzyl alcohols by catalytic reduction of the corresponding tetrafluoroterephthalonitrile via the intermediates tetrafluoroterephthalaldehyde tetraalkyl acetal and tetrafluoroterephthalaldehyde. However, in the case of the preparation of 2,3,5,6-tetrafluorodibenzyl alcohol, a purity of only 93.4% is obtained. The total yield, starting from 2,3,5,6-tetrafluoroterephthalonitrile, is 48% (see Examples 15 and 18 in this document). Also described is the synthesis of 2,3,5,6-tetrafluorobenzyl alcohol by the same process. The yields of about 80% and the purities of >99% described in a number of examples in this document are considerably higher than those in the synthesis of the corresponding dibenzyl alcohol.
The synthesis of 2,3,5,6-tetrafluorodibenzyl alcohol is also described in the as yet unpublished German patent application with the reference 100 03 320, by hydrogenation of 2,3,5,6-tetrafluoroterephthalonitrile to 2,3,5,6-tetrafluorodibenzylamine and subsequent diazotization and heating of the amine. The 2,3,5,6-tetrafluorodibenzyl alcohol obtained in this manner has a purity of 74.5%; however, for certain applications, this is still not entirely satisfactory. According to the example, the total yield starting from 2,3,5,6-tetrafluoroterephthalonitrile is 52.1%.
WO-A-00/68173 describes a process in which, comparably to the process of the German patent application with the reference 100 03 320, 2,3,5,6-tetrafluorobenzyl alcohol is prepared from 2,3,5,6-tetrafluorobenzonitrile. The purity of 99.3% and the yield of 85.1% achieved here are considerably higher than those achieved in the synthesis of the corresponding 2,3,5,6-tetrafluorodibenzyl alcohol.
DE-A-37 14 602 describes a process for preparing 2,3,5,6-tetrafluorobenzyl alcohols which may be substituted in the 4-position by a methyl radical, by reacting 2,3,5,6-tetrafluorobenzoic acids which may be substituted in the 4-position by a methyl radical with sodium borohydride and then with an alkylating agent in the presence of a diluent at temperatures between −20° C. and +150° C. The reaction of the tetrafluorobenzoic acids is preferably carried out at 0-30° C. and the subsequent reaction with the alkylating agent is preferably carried out at 0-100° C., where from 0.5 to 0.9 mol of an alkylating agent are employed per mole of starting material. The process affords the 2,3,5,6-tetrafluorobenzyl alcohol in a yield of 96.7% and a purity of 98%.
The hydrolysis with sulfuric acid of 2,3,5,6-tetrafluoroterephthalonitrile to 2,3,5,6-tetrafluoroterephthalic acid is described in EP-A-0 749 409.
As is known to the person skilled in the art, the use of insecticides, in particular household insecticides, is preceded by intensive toxicological studies. As a consequence, it is desirable to be able to employ the active compounds in a defined form which is as pure as possible. In the synthesis of insecticides—in particular when 2,3,5,6-tetrafluorodibenzyl alcohol is used—the byproducts which are substituted asymmetrically in the benzyl position, such as 1-(benzyl alcohol)-4-benzylamines, 1-benzaldehyde-4-benzyl alcohols and 1-(benzoic acid)-4-benzyl alcohols are disruptive, since these compounds can pass through the entire synthesis and even into the end product, and may therefore remain in the active compound and can exert undesirable toxic effects.
All of the three processes for preparing 2,3,5,6-tetrafluorodibenzyl alcohols mentioned above (GB-A-2,127,013, WO-A-00/68173 and DE-A-100 03 320) have in common the disadvantage that, starting from tetrafluoroterephthalonitrile, the reaction proceeds via more than one intermediate. An additional, decisive disadvantage is the fact that in all other processes used both for preparing monobenzyl alcohols and dibenzyl alcohols, the dibenzyl compound is in each case obtained in a considerably poorer yield and purity. The conclusion that had to be drawn from these facts was that apparently the dibenzyl function of the desired product and the asymmetric intermediates formed during a synthesis greatly affect both purity and yield.
Accordingly, it was an object of the present invention to provide a process which allows the preparation of halogen-substituted dibenzyl alcohols starting from the corresponding halogen-substituted terephthalic acids, with high yields and purities and in particular substantially free of compounds substituted asymmetrically in the 1- and 4-positions.
SUMMARY
The invention relates to a process for preparing a halogen-substituted dibenzyl alcohol of the general formula (I):
wherein the radicals X are identical or different and are hydrogen, fluorine, chlorine or bromine and at least one X is fluorine, chlorine or bromine. The process comprises reacting (1) a halogen-substituted terephthalic acid of the general formula (II)
wherein the radicals X are as defined for the general formula (I) with (2) sodium borohydride and then with (3) an alkylating agent or sulfuric acid or an alkyl-sulfonic acid or an arylsulfonic acid, wherein the sulfuric acid or the alkyl-sulfonic acid or the arylsulfonic acid comprises at most 5% by volume of water and the sodium borohydride reacts in an organic solvent at a temperature ranging from about 0 to about 150° C.
The invention also relates to a halogen-substituted dibenzyl alcohol of the general formula (I):
wherein the radicals X are identical or different and are hydrogen, fluorine, chlorine or bromine and at least one X is fluorine, chlorine or bromine, wherein the alcohol is obtained by a process comprising reacting (1) a halogen-substituted terephthalic acid of the general formula (II)
wherein the radicals X are as defined for the general formula (I) with (2) sodium borohydride and then with (3) an alkylating agent or sulfuric acid or an alkylsulfonic acid or an arylsulfonic acid,
wherein the sulfuric acid or the alkylsulfonic acid or the arylsulfonic acid comprise at most 5% by volume of water and the sodium borohydride reacts in an organic solvent at a temperature ranging from 0 to about 150° C.
The invention also relates to a halogen-substituted dibenzyl alcohol of the general formula (I)
wherein the radicals X are identical or different and are hydrogen, fluorine, chlorine or bromine and at least one X is fluorine, chlorine or bromine, wherein the alcohol comprises at most 1.0% of compounds which are substituted asymmetrically in the 1- and 4-positions. These and other features, aspects, and advantages of the present invention will become better understood with reference to the following description and appended claims.
DESCRIPTION
The invention provides a process for preparing halogen-substituted dibenzyl alcohols of the general formula (I)
where the radicals X are identical or different and are hydro
Akoril Godfried R.
Bayer Aktiengesellschaft
Denesvich Jill
Eyl Diderico van
Shippen Michael L.
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