MXPA98000978A - Process for the production of halogen o-hidroxidifen compounds - Google Patents

Abstract

The present invention relates to: a four-step process for the production of o-hydroxydiphenyl halogen compounds having the formula (See Formula) X is -O- or -CH2-; M is between 1 and 3; and n is 1 and 2: in the first step, a diphenyl compound is chlorinated, in a second step the chlorinated compound is acylated in a Friedel-Crafts reaction, optionally again chlorine after acylation, in a third step the acyl compound is oxidized and in a four step the oxidized compound is hydrolyzed. The compounds of the formula (1) are useful for the protection of organic materials against microorganisms

Description

PROCESS FOR THE PRODUCTION OF HALOGEN- O-HYDROXIDIPHENYL COMPOUNDS The present invention relates to the production of halogen-o-hydroxydiphenyl compounds having the formula: wherein X is -O- or -CH2-; M is between 1 and 3; and n is 1 or 2; as well as the use of these compounds for the protection of organic materials against microorganisms or for example, in cosmetic compositions. The production of the halogen-o-hydroxydiphenyl compounds, especially of 2-hydroxy-2,4'-trichlorodiphenylether (Triclosan, a compound of the formula (3) below), is generally carried out by means of diazotization and subsequent hydrolysis of 1-amino-2 ', 4,4'-trichlorodiphenylether (TADE, compound of the formula (2) below): The yields obtained by means of this production method are not satisfactory, however, since several chemically competing reactions can occur. The object of the present invention, therefore, is to provide a process for the production of halogen-o-hydroxydiphenyl compounds in which unwanted side reactions are suppressed. In accordance with the present invention, there is provided a four step process for the production of halogen-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 chlorine after acylation; in a third step the acyl compound is oxidized; and in a four step the oxidized compound is hydrolyzed; according to the following reaction scheme: (4) 4. hydrolysis In the above scheme: R is a C? -C8 alkyl or C? -C8 alkyl substituted by 1 to 3 halogen atoms or hydroxy; or aryl of unsubstituted C6-C? 2 or C6-C? 2 aryl substituted by 1 to 3 halogen atoms, C1-C5 alkyl or d-C8 alkoxy or combinations thereof: X is -0- or -CH2 -; m is 1 to 3; and n is 1 or 2. Ci-Cß alkyl denotes branched or unbranched alkyl such as, for example, 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-methyl-heptyl, 3-methylheptyl, 2 -ethylhexyl or n-octyl. The C?-C8 alkoxy are branched or unbranched residues such as, for example, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexyloxy, heptyloxy or octyloxy. The halogen denotes fluorine, bromine or preferably chlorine. In the above reaction scheme, in formulas (6) and (7), preferably R is a C 1 -C 4 alkyl, especially methyl. For the first reaction step, a chlorinating agent, for example sulfuryl chloride or, preferably chlorine gas, can be used. The reaction is preferably carried out in the presence of a catalyst such as, for example, dibenzothiophene, methyl sulphide, propyl sulfide, phenyl sulfide, a Lewis acid such as for example aluminum chloride or mixtures of these compounds. Especially suitable as a catalyst for the chlorination reaction according to the invention is a mixture of propyl sulfide and an equimolar amount of aluminum chloride. For the reaction in the first step, the temperature can be selected within a wide range, for example, between -10 to 50 ° C. Preferably, the reaction is conducted at a temperature between 0 and 40 ° C: The reaction time can also vary within a wide range. Usually the reaction is carried out within a time range of 1 to 48, preferably 2.5 to 10 hours. The acylation reaction (second step) is generally carried out in the presence of a Lewis acid, for example, aluminum chloride. The Lewis acid can be used in amounts of 1 to 3 molar, preferably 1, 25 to 2 molar amounts, based on the chlorinated compound of the formula (5). An acylating reagent suitable for use in this reaction is an acyl halide, preferably acetyl chloride. In addition, suitable acylating agents are, for example, The Lewis acid and acylating reagents are preferably used in molar amounts. The reaction can be carried out in solvents which are conventionally used for Friedel-Crafts reactions, such as, for example, halogenated solvents such as, for example, methylene chloride or ethylene chloride. The reaction time for this reaction step is of secondary importance and can vary within a wide range, for example, between 1 and 18 hours. After the acylation reaction, the reaction mixture can optionally be subjected to another chlorination reaction, analogously to the first reaction step, especially if, in the first step of the reaction, mixtures of diphenyl compounds are obtained. They are mixed in different ways, such as, for example, mixtures of 4,4'-dichlorodiphenyl- and 2,4,4'-trichlorodiphenyl compounds. By means of the sub-following chlorination, uniformly chlorinated acyl compounds are produced.

The chlorination reaction (first step) and the acylation reaction (second step) and the subsequent optional chlorination reaction are preferably carried out in the same reaction vessel, which is in single crucible reactions.

Oxidation of the acyl compound of the formula (6) gives the compound of the formula (7) (Baeyer-Villiger oxidation), can be carried out with various oxidizing agents. Suitable oxidizing agents are, for example: an equimolar mixture of dilute peracetic acid and acetic anhydride in the presence of a catalytic amount of perchloric acid; an excess of 3-chloroperbenzoic acid in water; di-peroxidodecanedioic 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 K2S208, sulfuric acid and a 1: 1 mixture of water / methanol; a mixture of acetic acid and the potassium salt of monoperoxomaleic acid; a mixture of trichloromethylene, 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 complex of urea-hydrogen peroxide and acetic acid; and Mg-mono-perftalate. Preferably, a mixture of maleic anhydride, a complex of urea-hydrogen peroxide and acetic acid as solvent is used for oxidation. If desired, a commercially available wetting agent may be added to the oxidizing agent. The reaction times are within a wide range and can vary between about 1 hour to about a week, preferably between 4 to 6 days. The reaction temperature is within the range between -20 ° C to around 80 ° C. Preferably, the reaction is carried out at room temperature. The final hydrolysis to the desired halogen-o-hydroxyphenyl ethers of the formula (1) proceeds quantitatively. Preferably, the process according to the invention relates to the production of halogen-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.

The compound of the formula is especially preferred Some of the acyl compounds formed in the second reaction step (Friedel-Crafts acylation) are new compounds. These are the compounds that have the formula wherein R is unsubstituted Ci-C8 alkyl or d-C8 alkyl substituted with 1 to 3 halogen atoms or hydroxy; or aryl of unsubstituted C 1 -C 2 or C 6 -C 2 aryl substituted by 1 to 3 halogen atoms, Ci-C 5 alkyl or Ci-Cβ alkoxy or combinations thereof. IN formula (8), preferably R is a Ci-C4 alkyl, especially methyl. These new compounds represent another aspect of the present invention. The halogen-o-hydroxydiphenyl compounds produced according to the invention are insoluble in water but are soluble in a solution of potassium and sodium hydroxide and in practically all organic solvents. Due to these solubility properties, the application of the compounds to combat microorganisms, especially bacteria, and to protect organic materials against attack by microorganisms is very versatile. In this way, they can be used, for example, together with the wetting or dispersing agents, such as, for example, soaps or solutions of synthetic detergents for the disinfection and cleaning of the human skin and hands, or they can be applied of solid articles in diluted form. or not diluted. The following Examples further illustrate the invention, but without limiting it.

Example 1a): Cloning of diphenyl ether and the direct use of the reaction product for its reaction with acetyl chloride. Diagram of the reaction acrylation Friedel-Crafts A mixture of 265 g (1.56 mol) of diphenylether (formula 101a, 7.36 g (0.06 mol) of dipropyl sulfide and 7.46 g (0.06 mol) of ALCI3 are placed in a container of The reaction is carried out by stirring and warming up to 30 ° C. The chlorination is carried out by introducing chlorine gas at a rate such that the reaction mixture can be maintained at a temperature below 40 ° C and by means of external cooling. The reaction was monitored using gas or liquid chromatography.Cl chlorination was stopped when the content of 2,4,4'-trichlorodiphenylether (compound of formula 101b) reached 80% of the area (about 6 hours of introduction time) For the acylation, 265 g (3.37 mol) of acetyl chloride, in the form of drops, were added over 450 g (3.37 mol) of AICI3 in 1100 ml of 1,2-dichloroethane, at 20 ° to 40 ° C. C. The reaction mixture was stirred for 15 minutes at 40 ° C. Finally, the solution was added, in the form of drops, to the mixture. of the chlorination reaction in 800 mls x of dichloroethane at a temperature of 40 ° C, for about an hour. The reaction mixture was then stirred for 10 hours at about 40 ° C. The reaction mixture was worked with 4 kg of ice and 550 ml of Concentrated HCl and extracting it for a short time. An aqueous phase and an organic phase formed which separated. After distilling the solvent from the organic phase, a dark, viscous residue remains which crystallizes upon settling. Yield: about 490 g of the reaction mixture was used; the content of the main component around 340 g, corresponding to about 70% of the theory, based on diphenylether (formula 101a). Main component: 2-acetyl-4,2,4'-trichlorodiphenylether corresponding to formula (101c).

Composition of the reaction mixture% GC or LC area): about 70% of the main component, about 15% 2,2 ', 4,4'-tetrachlorodiphenylether with the remainder being unknown compounds. The reaction mixture can be used directly for the subsequent Baeyer-Villiger oxidation (Example 1b). Example 1b): Baever - Villiaer oxidation Reaction scheme: 6.32 g of 2-acetyl-4,2,4'-trichlorodiphenylether corresponding to formula (101c) produced in Example 1a) and 6.88 g of m-chloroperbenzoic acid (MCPBA) were dispersed with a wetting agent in 40 meters of water at 20 to 25 ° C. The suspension was heated to 80 ° C and maintained at this temperature, with vigorous stirring, for 3 hours. 20 ml of tetrachlorethylene were added where two clear phases were formed. The excessive peracid was decomposed by adding 0.5 g of sodium hydrogen sulfite, the mixture was adjusted to a pH value of about 8 with NaOH and the aqueous phase (containing m-chloroperbenzoic acid) was separated. The phenolether of the formula (101d) can be recovered, as a white powder with a p. F. 48-49 ° C; by means of the crystallization of the organic phase.

For hydrolysis, some water was added to the organic phase and the pH value was adjusted to 12 with sodium hydroxide. The final product of the formula (101) was obtained from the intermediate product of the formula (101 d). The pH value was adjusted to about 1 with hydrochloric acid, the aqueous phase was separated and the tetrachlorethylene phase was concentrated. 5.7 g of a yellowish oil containing about 80% area of the compound of the formula (101) were obtained. After recrystallization of the petroleum ether, the product was obtained as a white powder having a melting point of between 55 to 56 ° C. The data agrees with those of the original compound. Example 1c): Baeyer oxidation - Villiqer alternative in the anhydrous medium To a solution of 3 g (10 mmol) of 2-acetyl-4,2,4'-thclorodiphenylether corresponding to formula (101c) in 20 ml of anhydrous dichloromethane, 4.5 g (13 mmol) of m-chloroperbenzoic acid was added. The mixture was cooled to 0 ° C and 0.77 ml (10 mmol) of trifluoroacetic acid was added. The reaction mixture was allowed to warm slowly to room temperature. After a reaction time of 8 hours at room temperature, the reaction mixture was cooled with a sodium sulfite solution and washed with a saturated sodium bicarbonate solution. The dichloromethane layer was washed several times with water, dried over anhydrous sodium sulfate and concentrated until an oily residue was obtained. This residue was hydrolyzed by boiling it for 15 hours, under reflux, in 10 ml of 1 N NaOH solution. 2 g of a crude reaction product were obtained which, after acidification, was purified by column chromatography. In this manner, 1.5 g (54% theory) of the compound of formula (101) was formed as a white crystalline powder. Alternative hydrolysis 0.9 g of the crude product obtained from the Baeyer -Villiger oxidation was boiled for 4 hours under reflux in 5 ml of ethanol containing a few drops of concentrated HCl. The reaction was monitored by thin layer chromatography. After completing the reaction, the alcohol was distilled in vacuo. The oily residue was dissolved in more dichloromethane and the solution was repeatedly washed with water. The organic phase was dried over anhydrous Na 2 SO 4 and concentrated. 0.8 g of the crude compound of the formula (101) were formed. By recrystallization from petroleum ether, 0.64 g (70% theory) was obtained as a crystalline powder. Example 2: The procedure of Example 1 a) was repeated except that the chlorination was conducted in a solution of about 30% diphenyl ether in 1,2-dichloroethane.

Examples 3 to 6: For the acylation reaction described in Example 1a), in addition to the acetyl chloride, the acylating agents determined in the following Table 1 can also be used: Table 1 dichlorodiphenylether and a subsequent chlorination reaction Example 7a: Acylation Reaction scheme: In a three-necked sulfonation vessel equipped with a balanced pressure dropping funnel, a nitrogen gas inlet tube, a stirrer, and a safety tube, 480 ml of anhydrous 1,2-dichloroethane and 221.8 were placed. g (11.456 mol) of 88% aluminum chloride. The mixture was stirred and cooled in an ice bath under a nitrogen atmosphere. To this mixture was added 104 ml of freshly distilled acetyl chloride (114.4 g, 1.456 mol) over a period of 15 to 20 minutes. The exothermic reaction was allowed to cool to room temperature and the mixture was stirred for 30 minutes. A homogeneous dark brown mixture was formed, to which 251.9 g of a mixture containing 2,4,4'-trichlorodiphenylether (79%) was added in the form of drops, with stirring at room temperature for 15 to 30 minutes. (= compound of formula (101 b)) and 4,4'-dichlorodiphenylether (9%) (compound of formula 101b), dissolved in 480 ml of 1,2-dichloroethane anhydrous. The reaction was monitored by means of gas chromatography. After stirring for 15 hours at room temperature, the mixture was added to 500 ml of ice water containing 50 ml of concentrated HCl. After stirring for 15 minutes, the organic phase was separated from the aqueous phase. The aqueous phase was extracted twice with 2-dichloroethane, using 100 ml of 1,2-dichloroethane each time. The combined organic phases were washed 6 times with water using 500 ml of water each time and dried over anhydrous sodium sulfate. After removing the solvent, 244 g of a mixture containing the compound of the formula (101 c) and the compound of the formula (101 f) were obtained. This reaction mixture was used for the subsequent chlorination reaction.

Example 7b: Subsequent chlorination Scheme of the reaction In a sulfonation vessel equipped with a dropping funnel, a chlorine gas inlet tube, a stirrer, a safety tube and also a purification system for the acid vapors, 0.077 g (0.65 mmol) of 88% aluminum propyl sulfide and chloride in 120 ml of anhydrous 1,2-dichloroethane. The chlorine gas was introduced into this mixture for 15 minutes with stirring. After interrupting the supply of gas, 244 g of a mixture containing 2-acetyl-2,4,4'-trichlorodiphenylether (84.4%) and 2- was added in the form of drops for 1, 5 to 2 hours and acet, 4'-dichlorodiphenyl ether (1.9%), dissolved in 120 ml of 1,2-dichloroethane anhydrous. The chlorine gas was introduced with stirring for one hour. The reaction was monitored using gas chromatography. After completing the reaction, the mixture was added to the 500 ml of ice water containing about 15% HCl. The organic phase was separated and the aqueous phase was washed twice with 1,2-dichloroethane, using 100 ml of 1,2-dichloroethane each time. The combined organic phases were washed five times with a saturated sodium bicarbonate solution, using 200 ml of a sodium bicarbonate solution each time, then washed five times with water, using 200 ml of water each time, and dried over sodium sulfate. Finally, the solvent was removed under vacuum. 240 g of a crude product containing the compounds of formulas (101c) and (101g) were obtained.

Example 8: Acylation Diagram of the reaction: To a 500 ml three-neck round base vessel equipped with a drip funnel with pressure equalizer, an overhead stirrer and a safety tube, 80 ml of 1,2-dichloroethane (EDC) and 9.85 g were added. of AICI3 (0.0664 mol) under an atmosphere of N2. The mixture was cooled to 15 ° C using a water bath, and stirring to 4.7 ml of acetyl chloride (5.18 g., 0.0660 mol) was added in the form of drops over a period of 30 to 45 minutes. To the above complex 10 g of a mixture of the compound of the formula (101e) (4,4'-dichlorodiphenylether, DCDPE), the compound of the formula (101 b) (2,4,4'-t chlorodiphenylether, TCDPE) was added. ) and 2,2 ', 4,4, -tetrachlorodiphenylether (0.0333 mol, room temperature, DCDPE and TCDPE together, TetCDPE) dissolved in 20 ml of EDC in the form of drops under stirring for a period of 20 minutes at room temperature . When adding the clohpante mixture no significant increase in temperature was noticed. The reaction begins to reflux and the reaction is monitored by GC (using FID and area normalization) at regular intervals. The reaction took one hour to complete the conversion of TCDPE into the compound of the formula (101c). During the conversion, 2.3% of the compound of the formula (101 h) (= xanthene) was also formed. The table below shows the course of the reaction: Table 2a: degree of conversion Even in another reaction the amount of EDC was reduced from 10 volumes to 2 volumes and the reaction was carried out under identical conditions to the previous ones. Table 2b: degree of conversion Example 9: Acylation Diagram of the reaction To a three-neck round 20 I base vessel equipped with a drip funnel with pressure equalizer, an overhead stirrer, a safety tube, 7 I of dichloromethane (DCM) and 1088.2 g of AICI3 (7.328) were added. mol) under an atmosphere of N2. The mixture was cooled to 15 ° C using a water bath and under stirring 522.9 ml of acetyl chloride (575.2 g, 7.328 mol) was added over a period of 20 minutes. During this time the internal temperature of the reaction rose to around 20 ° C. The solution was stirred for a further 10 minutes when the solution became clear. To the above complex was added 1,100 g of a mixture of the compounds of formulas (101e) (DCDPE), (101b) (TCDPE) and 2,2 ', 4,4'-tetrachlorodiphenylether (3.664 mol, weight room temperature. and TCDPE together) dissolved in 4,000 ml of DCM under stirring over a period of 20 minutes together with a simultaneous heating of the reaction mixture. When adding the chlorinant mixture no significant increase in temperature was noted. The reaction will reflux after almost 1.5 hours. Sampling was carried out after a regular interval to estimate the degree of the reaction on the basis of GC (using FID and area normalization). The reaction took almost 22-24 hours for the conversion of TCDPE to the compound of formula (101c) (TCADPE). During the conversion, 1.3% of the compound of the formula (101 h) (xanthene) was also formed. The CG data shown in Table 3 show the conversion as a function of time: Table 3. Conversion degree Example 10: Baeyer - Villiger Oxidation Reaction Scheme: ml of acetonitrile was placed in a 50 ml round base vessel and 0.75 g (0.0079 mol) of a urea-hydrogen peroxide complex (UHP) and 92 mg (0.0008 mol) of maleic acid To this stirred heterogeneous mixture, 0.75 g (0.0076 mol) of maleic anhydride was added in portions at room temperature for 10 minutes. To the above solution was added 0.25 g (0.008 mol) of the compound of the formula (101 c). The reaction was then continued by stirring the reaction at room temperature. The reaction became clear after 45 minutes and was monitored by GC (FID detector and area normalization). After 19 hours the reaction proceeded to about 40% conversion. The distribution of the product was as follows (Table 4): Table 4: Product distribution Example 11: Baeyer-Villiqer oxidation (the reaction scheme corresponds to that of Example 10) 25 ml of trifluoroacetic acid and 5 ml (0.0441 mole) of a 30% hydrogen peroxide solution were placed in a round-bottomed container of 100 ml. The mixture was stirred for 15 minutes and, under stirring at room temperature, 5.0 g (0.0158 mol) of the compound of the formula (101 c) were added. The reaction was then continued by stirring the reaction at room temperature. The solution turned yellowish orange after about 15 minutes and was monitored by GC analysis (FID detector and area normalization).

The distribution of the product was as follows (Table 5): Table 5: Product distribution Example 12: Baever-Villiger oxidation (the reaction scheme corresponds to that of Example 10) 15 ml of acetic acid were subjected to a 50 ml two-neck round base vessel with a condenser and a dropping funnel. 4 ml (0.0280 mol) of a 70% solution of perchloric acid and 2.0 g (0.0063 mol) of the compound of the formula (101c) were added. The homogeneous mixture was heated with stirring to 70-75 ° C. Using a dropping funnel, 4.4 ml (0.0647 mol) of a 50% hydrogen peroxide solution was added dropwise over a period of 30 minutes. After completing the reaction, it was monitored by GC analysis (FID detector and area normalization). The distribution of the product was as follows (Table 6): Table 6: Product distribution Example 13: Oxidation of Baeyer-Villiger (the scheme of the reaction is that corresponding to Example 10) 10 ml of water were subjected to a 100 ml round-bottom container of two necks with a dropping funnel. 10 ml of H2SO4 were added slowly. 2.0 g (0.0063 mol) of the compound of the formula (101 c) (2-acetyl-2 ', 4,4'-trichloroacetyldiphenyl ether) were added and the 50% H 2 SO 4 solution was heated to 80 °. C. The temperature then rose to around 130 ° C. To this solution were added in the form of drops 3.6 ml (0.318 mol) of H2O2 in the form of drops over a period of about 15 to 20 minutes. After the reaction was completed, it was monitored by GC analysis (FID detector and area normalization). The distribution of the product is as follows (Table 7):

Claims (16)

1. CLAIMS 1. A four step process for the production of halogen-o-hydroxydiphenyl compound in which, in the first step, the diphenyl compound is chlorinated; in a second step, the chlorinated compound is acylated in a Friedel-Crafts reaction and optionally chlorine again after 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: (7) oxidation (6) 4. hydrolysis (1) In the above scheme: R is a C? -C8 alkyl or d-C? Alkyl substituted by 1 to 3 halogen atoms or hydroxy; or aryl of unsubstituted C6-C ?2 or C6-C? ar aryl substituted by 1 to 3 halogen atoms, C1-C5 alkyl or C?-C8 alkoxy or combinations thereof: X is -O- or - CH2-; m is 1 to 3; and n is 1 or 2.
2. 2. A process according to Claim 1 wherein the chlorination (first step) is conducted with elemental chlorine.
3. 3. A process according to Claim 1 or 2 wherein the chlorination is conducted in the presence of a mixture of propyl sulfide and an equimolar amount of aluminum chloride.
4. 4. A process according to any of Claims 1 to 3 wherein the other chlorination follows the acylation step.
5. 5. A process according to any of Claims 1 to 4 wherein the acylation reaction (second step) is conducted in the presence of acetyl chloride and aluminum chloride, where acetyl chloride and aluminum chloride are used in equimolar amounts.
6. 6. A process according to Claim 5 wherein the acylation reaction is conducted in the presence of a halogenated solvent.
7. A process according to any of Claims 1 to 6 wherein the chlorination (first step), the acylation reaction (second step) and optionally another acylation are conducted as a one-step reaction.
8. 8. A process according to any of Claims 1 to 7 wherein the oxidation (third step) is carried out with a mixture of maleic anhydride, a complex of urea-hydrogen peroxide and acetic acid as a solvent.
9. 9. A process according to any of Claims 1 to 8 wherein in the formulas (6) and (7) R is Ci-C4 alkyl.
10. 10. A process according to Claim 9 wherein R is methyl.
11. 11. A process according to any of Claims 1 to 10 wherein in formula (1) X is oxygen.
12. 12. A process according to any of Claims 1 to 11 wherein in formula (1) m is 1 and n is 1.
13. 13. A compound having the formula wherein R is a d-C8 alkyl or C? -C? 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:
14. 14. A compound according to Claim 13 wherein R is a Ci-C4 alkyl.
15. 15. A compound according to Claim 14 wherein R is methyl.
16. 16. The use of a compound produced according to the process claimed in any of Claims 1 to 12 for the protection of organic materials against attack by microorganisms.