NO129632B - - Google Patents

Description

2-Hydroxyalkyl esters of thiolsulfonic acids with

microbicidal activity.

This invention relates to new 2-hydroxyalkyl esters of thiolsulfonic acids with microbicidal activity. The compounds according to the invention are particularly useful for combating slime formation and other micro-organisms in industrial processes that include water and substances that are normally exposed to microbiological degradation or deterioration in the presence of water, where the growth and reproduction of such micro-organisms affect the actual process or affect the quality or character of the resulting product.

When wet or subjected to treatment in water, many industrial products are normally subject to microbiological degradation or deterioration if no action is taken to prevent such degradation or deterioration. Wood pulp, wood chips, starch and proteinaceous substances, animal hides, vegetable tanning fluids and leather are all damaged or degraded by the growth of micro-organisms or by enzymes produced by such growth.

An undesirable phenomenon that occurs in industrial process systems in which water is included is slime formation. Mucus consists of coating-like deposits of micro-organisms, fibers and debris, and it may be stringy, pasty, rubbery, tapioca-like, hard or horny, and it may have a characteristic odor different from that of the liquid suspensions that it is formed in. The micro-organisms that take part in this formation are mainly different species of spore-forming and non-spore-forming bacteria, especially encapsulated forms of bacteria that secrete gelatinase substances that enclose or enclose the cells. Slime-forming micro-organisms also include filamentous bacteria, filamentous fungi of the mold type, yeasts and yeast-like organisms.

Besides being undesirable for reasons of general cleanliness and hygiene in breweries, wineries, dairies, paper mills and other industrial plants or businesses, slime can affect and cause clogging of screens in pulp and paper systems and thus reduce their efficiency. When large amounts of slime are incorporated into the paper cloth, its strength is reduced and it can therefore go

in pieces and require the machine to be rewired. In the paper itself, slime can cause unsightly stains, holes and smells and can cause a general discolouration of the entire paper.

The compounds according to the invention are also effective in combating the growth and reproduction of sulphate-reducing bacteria. This is not only very desirable, but also very unexpected, because it has been very difficult to combat the growth of sulfate-reducing bacteria by means of bactericides. With regard to the difficulties that have hitherto been encountered in combating such bacteria, reference should be made to the article by G.J.Guynes and E.O. Bennett entitled "The Sensitivity of Sulfate-Reducing Bacteria to Anti-Bacterial Agents", published in Producers Monthly, November 1958. These authors studied the effects of 28 organo-mercuric compounds and 63 phenolic compounds on such bacteria. Of the organomercury compounds, none inhibited the growth of sulfate-reducing bacteria at concentrations as low as 50 parts per million. This is the case despite the fact that organomercury compounds are generally the most effective and applicable bacteriostatic compounds known. In many cases, these compounds will inhibit the growth of bacteria other than sulphate-reducing bacteria in a concentration of less than 1 part per million.

Of the phenolic compounds studied, which are also known for their general effectiveness, only three reduced the growth of sulfate-reducing bacteria at concentrations as low as 25 parts per litre.

million.

Used in agriculture, the organic thiol sulfonates according to the invention can be used as seed, plant and soil bactericides for the protection of seeds, seedlings and plants against bacterial attack.

The purpose of the present invention is thus to provide new organic 2-hydroxyalkyl esters of thiolsulfonic acids, which overcome the disadvantages of the previously known microbicides.

According to the invention, new microbicide 2-hydroxyalkyl esters of thiolsulfonic acids are provided with the general formula:

where R is an alkyl group containing 1 - 10 carbon atoms, a substituted alkyl group containing 1 - 10 carbon atoms where 1 or more of the hydrogen atoms are replaced by halogen, hydroxyl, alkoxy, cyano, amino or nitro; an aryl group; a substituted aryl group in which 1 or more of the hydrogen atoms are replaced by halogen, alkoxy, cyano, hydroxyl, amino, nitro or lower alkyl; or an aralkyl group; and R' is an alkyl group containing 1-8 carbon atoms, chloromethyl or phenyl. The 2-hydroxyalkyl esters of thiolsulfonic acids can be prepared by several methods, of which the following are examples: 1. An alkali metal sulfate of a thiolsulfonic acid is reacted with a 1-halo-2-hydroxyalkane^

A similar procedure is described by Boldyrev and colleagues

in the Russian journal Zh. Org. Kim. 3(1) 37-40 (1967), but the method stated there is significantly inferior to the present method. In the preparation of S-2-hydroxyethyl thio-4-biphenylsulfonate, 2-bromoethanol was reacted for 30 days to give a yield of only 25.8% of the resulting thiolsulfonate. Compared to the reaction time of two hours in the following example 4, and the yield of 83.6%, this clearly shows that. according to the invention, this is a significant improvement.

2. A thiolsulfonic acid is reacted with a 1,2-epoxide:

The solvents used in the reaction can include water, alcohols, ketones, dimethylformamide, etc. The reaction components are usually used in approximately equal parts by mole.

Other thiol sulfonates which are effective as bactericides are described in the chemical literature and the patent literature. Some of these compounds possess some of the properties required of industrial microbicides, but the 2-hydroxyalkyl esters of thiolsulfonic acids are soluble in water or common, cheap, organic solvents, are stable under ordinary conditions of use and storage, have sufficiently high vapor pressures to that odor and eye irritation are not a problem, and can be easily produced from readily available raw materials with a good yield.

Boldyrev et al. (Jour. Gen. Chem. U.S.S.R. 33:1926-1928 (1963)) has described the 2-hydroxyethyl esters of several thiol sulfonic acids. These authors state that 2-chloroethyl thiol sulfonates are powerful fungicides, although their antibacterial activity is often lower than that of the chlorine-free alkyl esters. however, it is reported that the 2-hydroxyethyl esters have a lower antimicrobial activity, even though the simplest 2-hydroxyethyl alkanethiol sulphonates are still relatively active. No further details are given in the article. Compared to this, we have now found that the homologue of 2-hydroxyethyl methanethiol sulfonate, namely, 2^-hydroxypropyl methanethiol sulfonate, is actually more effective as a bactericide than 2-chloroethyl ethanethiol sulfonate despite the statements in the above-mentioned article. A solution containing 35% 2-hydroxyethyl methanethiolsulfonate also had an acute oral toxicity (LD^q)

of 355 milligrams per kilograms of body weight when tested on male and female rats.

A similar 35% solution of the homologous compound 2-hydroxypropyl methanethiolsulfonate had an acute oral toxicity (LD, -0)

of 712 milligrams per kilograms of body weight in male and female rats. The significance of this difference in toxicity is obvious, since the 2-hydroxyethyl methanethiolsulfonate solution would be classified under category II by the Pesticides Regulati<p>n Division of the United States Department of Agriculture, while the 2-hydroxypropylmethanethiolsulfonate solution would be classified under category III. Category III products are considered significantly less hazardous and require less stringent label precautions in accordance with the Federal Insecticide, Fungicide and Rodenticide Act. These facts show that the compound 2-hydroxypropyl methanethiolsulfonate according to the invention possesses unexpected and important advantages compared to the homologous compound 2-hydroxyethyl methanethiolsulfonate described by Bodyrev et al.

Many of the compounds according to the invention are soluble

in water or in common organic solvents such as alkyl and aromatic hydrocarbons, alcohols, ketones, esters, ether alcohols, dimethylformamide, dimethylsulfoxide and other solvents. Addition of a surface-active agent to the liquid or solution makes the less water-soluble compounds according to the invention easily dispersible in water. In general, nonionic dispersants are preferred. Examples of such preferred nonionic dispersants include alkylphenoxypolyoxyethylene ethanol or alkylpolyoxyethylene ethanol. However, it should be understood that suitable dispersants are not limited to these.

Regarding the amount of the compounds that can be added to aqueous systems when used to control microorganisms, suitable amounts range from 0.05 to 1000 parts per part. million parts of water. It should of course be understood that larger quantities can be used, but such larger quantities increase operating costs without corresponding benefits being achieved.

The following examples shall serve to further illustrate the invention.

EXAMPLE 1

2- hydroxypropyl methanethiol sulfonate

A 500-ml reaction flask was charged with 150 ml of water, 48.0 grams

(0.2 mole) of sodium sulfide nonahydrate and 1.6 grams of sodium hydroxide. The temperature was lowered to 10-15°C, and 22.8 grams (0.2 mol) of methanesulfonyl chloride was added dropwise. Sulfur precipitated during the addition, but redissolved after the reaction mixture was heated under reflux for 1 hour. The reaction mixture was cooled and neutralized with acetic acid

and then treated with 12.0 grams (0.2 mole) of additional acetic acid and 17.4 grams (0.3 mole) of propylene oxide at 0°C. The reaction flask was then packed in ice, and the contents were stirred overnight.

The reaction mixture was then extracted with three 50-ml portions of methylene chloride, and the extract evaporated on a rotary evaporator. The residue, which contained both solid and liquid, was filtered, and the filtrate was dissolved in methylene chloride, washed with 15 ml of water and evaporated again. The product was obtained as a yellow liquid and amounted to 15.1 grams (44%). The 2-hydroxypropyl methanethiol sulfonate as well as the other 2-hydroxy substituted esters of thiolsulfonic acids prepared in Examples 2-5 along with those included in Table I were characterized by their infrared spectra.

EXAMPLE 2

2 - hydroxybutyl methanethiolsulfonate,

A 1000-ml reaction flask was charged with 511 ml of an aqueous solution containing 0.5 mol of sodium methanesulfonate which had been neutralized with acetic acid, and 72.0 grams (1.0 mol) of butylene oxide. The reaction mixture was heated under reflux in 30 minutes, cooled and extracted with methylene chloride. The extract was dried with anhydrous magnesium sulfate and the solvent was evaporated. The yield of pale green 2-hydroxybutyl methanethiolsulfonate was 50.9 grams (55%).

EXAMPLE 3

2 - h ydrok sv - 2 - fe ny le tv 1 - me tan t io 1 su 1 f ona t

The method according to example 2 was used to prepare

the liquid compound 2-hydroxy-2-phenylethyl methanethiolsulfonate in a yield of 43% from styrene oxide and sodium methanethiolsulfonate.

EXAMPLE 4

3-chloro-2-hydroxypropyl-butanethiol sulfonate

A 1000 ml reaction flask was charged with 283 grams of an anhydrous solution containing 31.1% sodium butanethiolsulfonate (0.5 mol). The solution was treated with 30.0 grams (0.5 mole) of glacial acetic acid which

was added dropwise over the course of 5-10 minutes at 25°C, and then with 46.3 grams (0.5 mol) of epichlorohydrin which was also added

added drop by drop over 5-10 minutes at 25-27°C. The temperature rose slowly to 45°C, and after 2 hours two layers were present. The reaction mixture was extracted with 100 ml of methylene chloride and then with 50 ml. The combined extracts were washed with water,

dried with anhydrous magnesium sulfate, and the solvent was evaporated. The yield of 3-chloro-2-hydroxypropyl-butanethiol sulfonate was 105.6 grams as an amber oil of 83.6% purity as determined by thiol sulfonate analysis.

EXAMPLE 5

3-chloro-2-hydroxypropyl-ethanethiol sulfonate

The method of Example 4 using sodium ethanethiolsulfonate solution was used to prepare a liquid product containing 76% 3-chloro-2-hydroxypropyl ethanethiolsulfonate in 65% yield.

The other 2^-hydroxy substituted esters of the thiolsulfonic acids which are

included in Example 6 as indicated in Table I, was prepared

using the preceding method.

EXAMPLE 6

The 2-hydroxyalkyl esters of the thiolsulfonic acids listed in Table I

was tested using the pulp-substrate method described in U.S. Pat. patent no. 2,881,070, using Aerobacter aerogenes and pulp substrates that were buffered to pH values of 5.5, 6.5 and 7.5, respectively. The results are summarized in Table I.

EXAMPLE 7

The effect of 2-hydroxypropyl methanethiol sulfonate on the growth of the sulfate-reducing bacterium Desulfovibrio desulfuricans was determined using the method described in Example 1 of U.S. Pat. patent No. 3,198,733. The results are shown in table 2.

Especially for agricultural purposes, the organic compounds in

according to the invention is used diluted with a carrier which can be liquid or solid. Dust can be produced with a fine-

split, solid material such as sora talc, clay, pyrophyllite, diatomaceous earth, hydrated silicic acid, calcium silicate or magnesium carbonate. Optionally, wetting and/or dispersing agents can be used. When the proportions of these are increased, you get a wettable powder that can be dispersed in water and applied from a shower.

Dust can contain 1-15% of one or more of the compounds in

according to the invention, while wettable powders may contain up to 50% or more of one or more of these compounds.

A typical composition of a wettable powder is 20-50% of the organic compounds, 45-75% of one or more finely divided solids, 1-5% of a wetting agent and 1-5% of a dispersing agent. Typical wetting agents include sodium dodecyl sulfate, sodium nonylbenzene sulfonate, sodium dioctyl sulfosuccinate, octyl-phenoxy-polyethoxyethanol, or other non-ionic agents such as ethylene and/or propylene oxide condensates with long-chain alcohols, mercaptans, amines or carboxylic acids. Typical dispersants include the sodium sulfonate of naphthalene-formaldehyde condensates and lignin sulfonates.

Liquid concentrates can also be used. For compounds according to the invention which are solid substances, the concentrate can be prepared by taking up the organic compound in an organic solvent together with one or more surfactants. E.g. one can mix 60 parts of one of the organic compounds, 10 parts of a surface-active, solvent-soluble alkylphenoxypolyethoxyethanol and 30 parts of aromatic white spirit or xylene.

The compounds according to the invention can be used together with other fungicidal agents and also together with miticides or insecticides or other pesticides.

Claims (3)

1. Microbicidal active compound, characterized in that it has the formula: where R is an alkyl group containing 1-10 carbon atoms or a substituted alkyl group containing 1-10 carbon atoms where one or more of the hydrogen atoms is replaced by halogen, hydroxyl, alkoxy, cyano, amino or nitro; an aryl group; a substituted aryl group in which one or more of the hydrogen atoms are replaced by halogen, alkoxy, cyano, hydroxyl, amino, nitro or lower alkyl; or an aralkyl group; and in R' is an alkyl group containing 1-8 carbon atoms, chloromethyl or phenyl. 2. Compound as indicated in number 1, characterized in that R and R' are methyl. 3. Compound as stated in claim 1, characterized in that R is methyl, and R' is ethyl.