Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
1998-02-05
2001-05-29
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S626000, C568S630000, C568S631000, C568S655000, C568S656000, C568S804000, C560S062000
Reexamination Certificate
active
06239317
ABSTRACT:
The present invention relates to the production of halogeno-o-hydroxydiphenyl compounds having the formula:
in which
X is —O—or —CH
2
—;
m is 1 to 3; and
n is1or 2;
as well as to the use of these compounds for the protection of organic materials against microorganisms or in e.g. cosmetic compositions.
The production of halogeno-o-hydroxydiphenyl compounds, especially of 2-hydroxy-2′,4,4′-trichlorodiphenylether (Triclosan; compound of formula (3) below), is usually effected by diazotisation and subsequent hydrolysis of 2-amino-2′,4,4′-trichlorodiphenylether (TADE; compound of formula (2) below):
The yields obtained by this production method are unsatisfactory, however, since various chemically competing reactions can occur.
The object of the present invention, therefore, is the provision of an economic process for the production of halogeno-o-hydroxydiphenyl compounds in which undesired side-reactions are suppressed.
According to the present invention, there is provided a four-step process for the production of halogeno-o-hydroxydiphenyl compounds in which, in the first step, a diphenyl compound is chlorinated; in a second step the chlorinated compound is acylated in a Friedel-Crafts reaction and optionally again chlorinated after the acylation; in a third step the acyl compound is oxidized; and in a fourth step the oxidized compound is hydrolyzed; according to the following reaction scheme:
In the above scheme:
R is unsubstituted C
1
-C
8
alkyl or C
1
-C
8
alkyl substituted by 1 to 3 halogen atoms or hydroxy; or unsubstituted C
6
-C
12
aryl or C
6
-C
12
aryl substituted by 1 to 3 halogen atoms, C
1
-C
5
alkyl or C
1
-C
8
alkoxy or combinations thereof;
X is —O—or —CH
2
—;
m is 1 to 3; and
n is 1 or 2.
C
1
-C
8
alkyl denotes branched or unbranched alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, sec.butyl, isobutyl, t-butyl, 2-ethylbutyl, n-pentyl, isopentyl, 1-methylpentyl, 1,3-dimethylbutyl, n-hexyl, 1-methylhexyl, n-heptyl, isoheptyl, 1,1,3,3-tetramethylbutyl, 1-methylheptyl, 3-methylheptyl, 2-ethylhexyl or n-octyl.
C
1
-C
8
alkoxy are straight-chain or branched residues such as methoxy, ethoxy, propoxy, butoxy, pentoxy, hexyloxy, heptyloxy or octyloxy.
Halogen denotes fluorine, bromine or, preferably, chlorine.
In the above reaction scheme, in formulae (6) and (7), preferably R is C
1
-C
4
alkyl, especially methyl.
For the first reaction step, there may be used, as chlorinating agent, e.g. sulfuryl chloride or, preferably, gaseous chlorine. The reaction is preferably conducted in the presence of a catalyst, such as dibenzothiophene, methyl sulfide, propyl sulfide, phenyl sulfide, a Lewis acid, such as aluminium chloride, or mixtures of these compounds. Especially suitable as catalyst for the chlorination reaction according to the invention is a mixture of propyl sulfide and an equimolar amount of aluminium chloride. For the reaction in the first step, the temperature can be selected from within a wide range, e.g. from −10 to 50° C. Preferably, the reaction is conducted at a temperature from 0 to 40° C. The reaction time can also vary within a wide range. Usually the reaction is conducted within a time span of 1 to 48, preferably 2.5 to 10 hours.
The acylation reaction (2. step) is usually conducted in the presence of a Lewis acid, e.g. aluminium chloride. The Lewis acid may be used in amounts of 1 to 3 molar, preferably 1.25 to 2 molar amounts, based on the chlorinated compound of formula (5). A suitable acylating reagent for use in this reaction is an acyl halide, preferably acetyl chloride. Further suitable acylating agents are e.g.
The Lewis acid and acylating reagents are preferably used in equimolar amounts. The reaction may be effected in solvents which are conventionally used for Friedel-crafts reactions, such as halogenated solvents like methylene chloride or ethylene chloride. The reaction time for this reaction step is of secondary importance and can be varied within a wide range, e.g. from 1 to 18 hours.
After the acylation reaction, the reaction mixture may optionally be subjected to a further chlorination reaction, in an analogous manner to the first reaction step, especially if, in the first reaction step, mixtures of differently chlorinated diphenyl compounds are obtained, such as mixtures of 4,4′-dichlorodiphenyl- and 2,4,4′-trichlorodiphenyl compounds. By the subsequent chlorination, uniformly chlorinated acyl compounds are produced.
The chlorination reaction (first step) and the acylation reaction (second step) and the optional further chlorination reaction are preferably conducted in the same reaction vessel, that is in one-pot reactions.
The oxidation of the acyl compound of formula (6) to give the compound of formula (7) (Baeyer-Villiger oxidation), may be effected with various oxidizing agents. Suitable oxidizing agents are, e.g.:
an equimolar mixture of dilute peracetic acid and acetic anhydride in the presence of a catalytic amount of perchloric acid;
an excess of 3-chloro-perbenzoic acid in water;
di-peroxydodecanedioic acid (DPDDA);
a mixture of dilute peracetic acid and acetic anhydride and sulfuric acid;
a mixture of m-chloroperbenzoic acid (MCPBA), trifluoroacetic acid and dichloromethane;
a mixture of sodium borate and trifluoroacetic acid;
a mixture of formic acid, hydrogen peroxide, acetic anhydride, phosphorus pentoxide and acetic acid;
a mixture of acetic acid, hydrogen peroxide, acetic anhydride and phosphorus pentoxide;
a mixture of K
2
S
2
O
8
, sulfuric acid and a 1:1 water/methanol mixture;
a mixture of acetic acid and the potassium salt of monoperoxomaleic acid;
a mixture of trichloromethylene, the potassium salt of monoperoxomaleic acid and sodium hydrogen sulfate;
a mixture of maleic anhydride, acetic anhydride, hydrogen peroxide and trichloromethane;
a mixture of maleic anhydride, a urea-hydrogen peroxide complex and acetic acid; and
Mg-mono-perphthalate.
Preferably there is used for the oxidation, a mixture of maleic anhydride, a urea-hydrogen peroxide complex and acetic acid as solvent.
If desired, a commercially available wetting agent may be added to the oxidizing agent.
The reaction times lie within a wide range and may vary from about 1 hour to about a week, from 4 to 6 days being preferred.
The reaction temperature ranges from −20° C. to about 80° C. Preferably, the reaction is conducted at room temperature.
The final hydrolysis to the desired halogeno-o-hydroxydiphenylethers of formula (1) proceeds quantitatively.
Preferably, the process according to the present invention relates to the production of halogeno-o-hydroxydiphenyl compounds having the formula (1) in which
X is oxygen, and especially those compounds in which
m is 2 and
n is 1.
Especially preferred is the compound of formula
Some of the acyl compounds formed in the second reaction step (Friedel-Crafts acylation) are new compounds. These are the compounds having the formula
in which
R is unsubstituted C
1
-C
8
alkyl or C
1
-C
8
alkyl substituted by 1 to 3 halogen atoms or hydroxy; or unsubstituted C
6
-C
12
aryl or C
6
-C
12
aryl substituted by 1 to 3 halogen atoms, C
1
-C
5
alkyl or C
1
-C
8
alkoxy or combinations thereof.
In formula (8), preferably R is C
1
-C
4
alkyl, especially methyl.
These new compounds represent a further aspect of the present invention.
The halogeno-o-hydroxydiphenyl compounds produced according to the invention are insoluble in water but are soluble in dilute sodium- and potassium hydroxide solution and in practically all organic solvents. Due to these solubility properties, the application of the compounds in combatting microorganisms, especially bacteria, and in protecting organic materials against the attack by microorganisms is very versatile. Thus, they can be used, e.g. together with wetting- or dispersing agents, as soaps or synthetic detergent solutions for the disinfection and cleaning of human skin and hands, or they can be applied to these from solid articles in diluted or undiluted form.
The following Examples further illustrate the invention, but without limiting
Ekkundi Vadiraj Subbanna
Kulkarni Surendra Umesh
Mudaliar Chandrasekhar Dayal
Nadkarni Pradeep Jeevaji
Nivalkar Kishore Ramachandra
Ciba Specialty Chemicals Corporation
Geist Gary
Mansfield Kevin T.
Owens Howard
LandOfFree
Process for the production of halogeno-o-hydroxydiphenyl... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the production of halogeno-o-hydroxydiphenyl..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the production of halogeno-o-hydroxydiphenyl... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2546008