CA2466954C - Antibacterial and antifouling oxathiazines and their oxides as coating compositions - Google Patents

Abstract

A coating composition comprising 3-aryl-5,6-dihydro-1,4,2-oxathiazines and their oxides having formula (a) wherein n is 0, 1 or 2; R1 is hydrogen, C1-4alkyl or benzyl; and R represents (i) phenyl; phenyl substituted with 1 to 3 substituents independently selected from hydroxyl, halo, C1-12alkyl, C5-6cycloalkyl, trihalomethyl, phenyl, C1-5alkoxy, C1-5alkylthio, tetrahydropyranyloxy, phenoxy, C1-4alkylcarbonyl, phenylcarbonyl, C1-4alkylsulfinyl, C1-4alkylsulfonyl, carboxy or its alkali metal salt, C1-4alkyloxycarbonyl, C1-4alkylaminocarbonyl, phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, dioxolanyl or C1-4alkyloxyiminomethyl; naphthyl; pyridinyl; thienyl, preferably when n is not 2; furanyl; or thienyl or furanyl substituted with one to three substituents, independently selected from C1-4alkyl, C1-4alkyloxy, C1-4alkylthio, halo, cyano, formyl, acetyl, benzoyl, nitro, C1-4alkyloxycarbonyl, phenyl, phenylaminocarbonyl and C1-4alkyloxyiminomethyl; or R represents a radical of formula (ii)

Description

ANTIBACTERIAL AND ANTIFOULING OXATHIAZINES
AND THEIR OXIDES AS COATING COMPOSITIONS

The present invention concerns a method of controlling bacteria and fouling organisms with 3-aryl-5,6-dihydro-1,4,2-oxathiazines and their oxides, a method of protecting non-living materials other than wood, and industrial antibacterial and antifouling compositions. Surfaces of objects -exposed to humid or aqueous environments are readily colonized by micro-organisms and occasionally by other, higher life forms such as molluscs and crustacea. As these organisms settle on or attach to said surfaces, the value of the exposed objects diminishes. The exterior, but possibly also the interior of the object may deteriorate, the surface changes (e.g. from smooth, clean and streamlined to rough, foul and turbulent), the weight of the object increases by the deposit of the organisms and their remnants, and the vicinity of the object may become obstructed or encumberecL The function of the object and system involved lowers and the quality of the aqueous environment deteriorates. Similar problems beset industrially used compositions such as coatings, lubricants and the like. All these phenomena are referred to as fouling. The oxathiazines of the present method and their oxides are disclosed in US-4,569,690 as herbicides, plant fungicides, plant desiccants and defoliants.

The present invention provides a method of controlling bacteria and fouling organisms;
said method comprising applying to said bacteria or fouling organisms, or to the locus thereof, an effective antibacterial or antifouling amount of a compound having the formula (~O, N
RI

SR. ~ =
[O]:, .
wherein n is 0, 1 or 2; R1 is hydrogen, Ci.4alkyl or benzyl; and R represents (a) phenyl; phenyl substituted with 1 to 3 substituents independently selected from hydroxyl, halo, CZ-12alicyl, C5{cycloalkyl, trihalomethyl, phenyl, C? -Salkoxy;
C1_5allcylthio, tetrahydropyranyloxy, phenoxy, C1,4allcy1carbonyl, phenylcarbonyl, CZ-4alkylsulfinyl, Cl-4alkylsulfonyl, carboxy or its alkali metal salt, Cl-4alkyloxy-carbonyl, C4-4allcylaminocarbonyl, phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl; amino, nitro, cyano, dioxolanyl or C14alkyloxyiminomethyl;
naphthyl; pyridinyl; thienyl, preferably when n is not 2; furanyl; or thienyl or furanyl substituted with one to three substituents independently selected from Cl-4allcyl, C1.4alkyloxy, C1..4allcylthio, halo, cyano, formyl, acetyl, benzoyl, nitro, Cl-4alkyloxy-carbonyl, phenyl, phenylaminocarbonyl and C1..4alkyloxyiminomethyl; or R
represents a radical of formula (b) wherein X is oxygen or sulfur, Y is nitrogen, CH or C(C1..4ai.kyloxy); and R"
is hydrogen or Ci.4alkyl.
The present invention in particular provides a method of protecting non-living materials other than wood, and the objects made of or covered by said non-living materials, against bacteria and/or fouling organisms, said method comprising applying to the surface or incorporating into said materials or objects an effective antibacterial or.
antifouling amount of a compound of formula (1).

In the foregoing definitions halo is generic to fluoro, chloro, brorno and iodo; CI-49cyl defines straight and branch chained saturated hydrocarbon radicals having from I to 4 carbon atoms comprising methyl, ethyl, n-propyl, 1-methyle:thyl, n-butyl, 1,1-dimethyl-ethyl,1-niethylpropyl, 2-methylpropyl; CI_5alkyl includes Cl.q.alkyl radicals as defined above and. saturated hydrocarlwn radicals having five carbon atoms, e.g. n-pentyl and the branched pentyl isomers; Cl-6alkyl includes Ci_galkyl radicals as defined above and six carbon containing homologs, e.g. n-hexyl and the branched hexyl isomers.
C1_12allcyl includes C1.6alkyl and saturated hydrocarbon radicals having from 7 to 12 carbon atoms, e.g. heptyl,,octyl, nonyl, decyl, undecyl and their isomers. The term alkali metal cation in particular is a sodium or potassium cati.on.
Trihalomethyl defines a methyl group being fully substituted with halo atoms, in particular trifluoromethyl and trichloromethyl. CZ -4alkyloxyiminomethyl defines a radical of formula -CH=N-O-C1.4alkyl=
Particular compounds of formula (1) for use in the method are those wherein n is 0, .1 or ,2; Rl is hydrogen, C14.alkyl or benzyl; and R represents phenyl; naphthyl;
pyridinyl;
thienyl provided that n is not 2; faranyl optionally substituted with 1 to 3 substituents independently selected from C?.-4aikyl and Ct-4aikyloxycarbonyl; or phenyl substituted with 1 or 2 substituents indepently selected from hydroxyl, halo, CI-12alkyl, C5-6cyclo-allcyl, trihalomethyl, phenyl, C2_5alkoxy, C1-5alkylthio, tetrahydropyranyloxy, phenoxy, Cl-aalkylcarbonyl, phenylcarbonyl, C1.4alkylsulfinyl, C1.4alkylsulfonyl, carboxy or its alkali metal salt, C1-5alkoxycarbonyl, Cl-4alkylaminocarbonyl, phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, or dioxolanyl.

Of interest are those compounds wherein n is 1 and R represents phenyl, thienyl or phenyl substituted with one or two substituents selected from halo and trihalomethyl; or those wherein n is 2 and R represents phenyl or phenyl substituted with one or two substituents selected from halo and trihalomethyl.

Of further interest are the compounds wherein R1 is hydrogen, n is 1 or 2, and R
represents phenyl, Cl-6alkylphenyl, halophenyl, dihalophenyl, biphenyl, CI-5alkyl-oxyphenyl, trihalomethylphenyl, nitrophenyl, phenyl substrituted with Cl.a,alkyloxy-carbonyl, C1-6alkylnitrophenyl, unsubstituted furanyl or thienyl, or furanyl or thienyl substituted with ethoxycarbonyl, cyano, chlorine or bromine:
Of particular interest are the compounds wherein R1 is hydrogen, n is 1 or 2, and R
represents 3-fluorophenyl, 4-chiorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-methylphenyl, 3-ethanonephenyl, 3-nitrophenyl, 3-methyl-4-nitrophenyl or 2-thienyl.
Also of further interest are those compounds of formula (I) wherein R1 is hydrogen, R
is a radical of formula (b) wherein X is sulfur, Y is nitrogen or CH, and R"
is hydrogen.
Preferred compounds are 5,6-dihydro-3-(2-thienyl)-1,4,2-oxathiazine-4-oxide and 3-(4-chlorophenyl)-5,6-dihydro-1,4,2-oxathiazine-4,4-dioxide.

All compounds of formula (I) can be prepared following the procedures described in US-4,569,690.

The compounds of formula (I) are active against gram-positive bacteria and, more importantly for use in material protection, also against gram-negative bacteria.

Susceptible bacteria belong to genera such as Aeromonas, Alcaligenes, Brevibacteriwn, Cellulomonas, Citrobacter, Corynebacteriurn, Enterobacter, Escherichia, Klebsiella;
Micrococcus, Proteus, Providencia, Pseudomonas, Shewanella, Acinobacter, Bacillus, Serratia, Staphylococcus, Streptococcus and Xanthomonas.

The compounds of formula (I) further are active against fouling organisms. The term "fouling organisms" is meant to comprise organisms that grow on or adhere to various kinds of surfaces, in particular in humid or aqueous environments such'as, marine waters, fresh waters, brackish waters, rain water, and also cooling water, drainage water, waste water and sewage. Fouling organisms are Algae such as, for example, Microalgae, e.g. Amphora, Achnanthes, Navicula, Amphipora, Melosira, Cocconeis, Chlamydomonas, Chlorella, Ulothrix, Anabaena, Phaeodactylum, Porphyridium;
Macroalgae, e.g. Enteromorpha, Cladophora, Ectocarpus, Acrochaetium, Ceramium, Polysiphonia; Molluscs, e.g. Mytilus, Crustacea, e.g. Artemea, Balanus, Elminius Modestus, Verruca, Lepas and Ascidia, Hydrozoa and Bryozoa.

The present invention also provides a method for the preservation of non-living snaterials other than wood against fungi that spoil or destroy such materials. Said method involves treating such materials with an effective fungicidal amount.of a compound of formula (I).
The compounds of formula (I) are useful to protect a wide variety of non-living materials other than wood, and the objects made thereof or covered thereby. Examples of non-living materials and the objects made thereof or covered thereby comprise adhesives;
sizes; paper and cardboard; pulp; textiles; leather; paints; plastics, e.g.
PVC and polyester, industrial compositions such as cooling media, e.g: cooling lubricants and cutting fluids, coating compositions, bath compositions (process liquids), lubricants and the like; metals and alloys such as iron and steel; building materials, e.g.
bricks, (paving) stones, cement and concrete; decorating materials, e.g. plaster, tiles; and any other materials that can be contaminated or destroyed by bacteria, fungi or fouling organisms.
Of particular interest are coating materials conventionally employed for decorative and protective purposes. The present method is especially suited for protecting adherent coatings, whether clear or colored (i.e. comprising one or more dyes or pigments), and whether natural or synthetic, such as, for example, paints - especially antifouling paint compositions -, varnishes, lacquers, finishes, whitewash and similar coatings.
The particular aptness. of the present method of protecting said coating materials resides in the fact that the oxathiazines employed in the method not only effectively protect the coating material in storage containers, during "in can" conservation (especially against bacteria) thus ensuring a long pot (or can) life and good storage stability, but alsq effectively protect the coating material and optionally its underlying substrate when it has been applied as a film to said substra.te ("film" conservation). The simultaneous utility of the oxathiazines for both "in can" and "film" conservation of coatings is of great practical value.
As constructions made of or covered by said non-living materials there can be mentioned swimming pools, baths, cooling water circulation circuits and industrial baths in various installations, e.g. in manufactering plants or in air-conditioning installations, the function of which can be impaired by the presence and/or the multiplication of bacteria and fouling organisms. Further examples are buildings and parts of buildings such as floors, outer and inner walls or ceilings, of places suffering from dampness such as cellars, bathrooms, kitchens, washing houses and the lil,ce, and which are hot-beds for bacteria and/or fouling organisms. The presence of these organisms not only is problemat ic from the viewpoint of hygiene and aesthetics, but also causes economic losses because said buildings and/or decorating materials deteriorate more rapidly than desired.
The method is especially suitable to protect underwater objects such as, for example, shiphulls, harbour installations, drying docks, sluice-gates, locks, mooring masts, buoys, drilling platforms, bridges, pipelines, fishing nets, cables and any other object in constant or frequent contact with water, by applying to said.objects an antifouling composition, e.g. paint composition, comprising an effective antifouling amount of a compound of formula (I).
In this context it should be noted that the present method provides a safer and ecologically more acceptable alternative for current methods using antifouling products based on heavy metals such as cuprous oxide and the like, or those based on organometallic derivatives such as organo-tin compounds. The toxicity of the oxathiazines to mammals is acceptable and as such they are less hazardous for humans whether these compounds reach the human body by direct physical contact (e.g.
during.
handling or application) or via the food chain. Their bio-degradability ensures that they are less persistent in the environment and that they cause less and shorter environmental pollution and stress. The chemical stability of the oxathiazines fiirthermore implies that they are compatible with most non-living materials as such and do not need special precautions such as the addition of agents for stabilizing the active ingredient. In materials that should form films such as lubricants, cutting fluids and coating materials, they do not impair the fomlation of uniform films and the practicability. In particular, in coating materials they do not impair rapid curing in practical circumstances such as room temperature and outdoor conditions, and allow for strong adhesion of the composition to the substrate and /or the topcoat.

The method of application is chosen in accordance with the intended objective and the prevailing circumstances. For instance, the technique used in the case of protecting lubricants, coatings or cutting fluids comprises mixing the active ingredient in said lubricants, coatings or fluids either during the manufacturing process or altematively -6-.
afterwards in the finished product. The active ingredient can be added in neat form or dissolved oz suspended in a sufficient amount of diluent. Preferably. the diluent consists of one or more of the solvents as they occur in the final composition.

The method also comprises applying compounds of formula (I), optionally in an appropriate formulation, to non-living materials by any of the techniques known,in the art such as, for example, brushing, spraying, atomising, dipping, soaking, immersing, scattering and pouring. In some instances, the application may involve impregnation techniques using pressure or vacuum systems, thermal systems, injection or diffusion.
Appropriate formulations are formulated following art-known procedures to emulsifiable concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, pastes, dusts, granulates, coating compositions, e.g. paints -in particular antifouling paint compositions -, lacquers and the like. For example, the active compound can be mixed with an extender, which consists of a liquid, semi-solid or solid carrier, and optionally surface-active agents such as emulsifiers and/oii dispersing agents. In coating compositions, the active compound may advantageously.
be incorporated in polymers, copolymers or resins. These can consist of such monomers as dialkyl (dimethyl) siloxanes, (meth)acrylic acid, (meth)acrylic acid esters, vinyl and allyl alcohols and derived esters (e.g. vinyl acetate), maleic acid, styrene, vinylchloride, butadiene, acrylamide, acrylonitrile and the liike copolymerizable monomers. As resins there may be mentioned alkyd resins, polyurethanes, epoxy resins, phenolic resins and urea-formaldehyde resins. Further useful additives in said compositions comprise water-repelling agents and surface slipping agents that are capable of imparting a low surface tension of the coating film formed by the polymer or copolymer in the coating compositions.

Any suitable carrier or additive that does not interfere with the antibacterial nor the .
antifouling activity of the active ingredient can be used in the compositions of the present invention. The solid carriers or fillers used e.g. for dusts and powders include various inert, porous and pulverous distributing agents of inorganic or organic nature such as, for example, the natural mineral fillers, e.g: calcite, talcum, kaolin, montmorilTonite or attapulgite,, or fillers of organic nature, e.g. powdered cork, sawdust and other fine pulverous materials. In order to improvt their physical properties it can be advantageous to add highly dispersed silicic acid or highly dispersed absorbent polymers.
Suitable granulated absorbent carriers are of the porous type, for example, pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are "imaterials such as calcite or sand. The active ingredient is mixed with these carrier substances, for example, by being ground therewith; alternatively, the inert carrier substance is impregnated with a solution of the active component in a readily volatile solvent and the solvent is thereafter removed by heating or by filtering with suction at reduced pressure. By adding wetti.ng and/or dispersing agents, such pulverous preparations can also be made readily wettable with water, so that suspensions are obtained upon dilution.
Inert diluents used for the production of liquid preparations should preferably not be readily inflammable and should be as far as possible non-toxic to nontarget animals or plants and humans in the relevant surrounding. Diluents suitable for this purpose are, for example, water or, organic solvents such as, for example, aromatic hydrocarbons, e.g. methylbenzene, dimethylbenzene mixtures, substituted naphthalenes;
alcohols and glycols and their ethers and esters, e.g. ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones e.g. 2-propanone, cyclohexanone and the like;
strongly polar solvents; e.g. N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide; vegetable oils or epoxidised vegetable oils such as epoxidised coconut oil or soybean oil, and mixtures thereof. Solutions can be prepared in the usual way, if necessary, with assistance of solution promotors. Other liquid forms which can be used consist of emulsions, dispersions or suspensions oi'the active compound in water or suitable inert diluents, or also concentrates for preparing such emulsions, dispersions or suspensions which can be directly adjusted to the required concentration.
For this purpose, the active ingredient is, for example, mixed with a dispersing, suspending or emulsifying agent. The active component can also be dissolved or dispersed in a suitable inert solvent and mixed simultaneously or subsequently with a dispersing or emulsifying agent. It is also possible to use semi=solid carrier substances of cream, ointment, paste or waxlike nature, into which the active ingredient can be incorporated, if necessary; with the aid of solution promotors and/or emulsifiers.
Vaseline, petroleum wax, liquid paraffin, silicone oil and other cream-bases are examples of semi-solid carrier substances. Furthermore, it is possible for the active ingredient to be used in the form of aerosols. For this purpose the active ingredient is dissolved or dispersed in a volatile liquid suitable for use as a propellant; for example, chlorinated and/or fluorinated derivatives of methane and ethane and mixtures thereof, or compressed air. In this way solutions under pressure are obtained which, when sprayed, yield aerosols that are particularly suitable for controlling or combatting bacteria and/or fouling organisms, e.g. in closed chambers and storage rooms. For the latter purpose also smoke generators containing the active ingredient can be used.

Besides the compounds of formula (I) and the carrier, appropriate formulations often comprise other adjuvants conventionally employed in the art of formulation.
These depend on specific applications and the user's preference. Such adjuvants are, for example, organic binding agents (e.g. chemically drying organic binder-forming polymers such as allcyd resins or physically drying organic binder-forming solids by solvent evaporation); insecticides such as, for example, chlorinated hydrocarbons, e.g.
endosulfan, organophosphates, e.g. chloropyriphos, pyrethroids, e.g.
permethrin and the like; additional fungicides and bactericides such as alcohols, e.g.
ethanol, 2,3,3-tri-iodallyl alcohol; aldehydes, e.g. formaldehyde, glutaraldehyde; formaldehyde releasing compounds, e.g. 2-bromo-2-nitro-propane-1,3-diol (bronopol), 2-bromo-2-nitro-propan-l-ol; reaction products of amines and formaldehyde, e.g. triazines, 3,5-dimethyl-tetrahydro-1,3,5-2H-thiadiazine-2-thione; reaction products of amides and formaldehyde, e.g. 1-hydroxymethyl-2-thiono-l:2-dihydzo-benzothiazol-N-hydroxymethylbenzothiazolinthione; phenols, e.g. 2-phenylphenol, pentachlorophenol;
organic acids, e.g. propionic acid, benzoic acid, salicylic acid, naphthenic acid copper ' salts; inorganic acids, e.g. boric acid; amides, e.g. 2,5-dimethyl-N-cyclohexyi-N-methoxy-furan-3=carbonarnide; carbamates, e.g. 3-iodopropargyl-N-butylcarbamate :
(IPBC), methyl-N-benzimidazol-2-ylcarbamate (Carbendazim), methyl-N-(1-butylcarbamoyl)benzimidazol-2-ylcarbamate (benomyl), zinc dimethyldithiocarbamate, zinc ethylenebisdithiocarbam ate, bis-(dimethylthiocarbamoyl)disulphide;
pyridine derivatives, e.g. 2-mercapto-pyridine-N-oxide, 2-chloro-6-(trichloromethyl)pyridine, 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine, copper 8-hydroxyquinoline, 1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid; azoles, e.g.
tebuconazole, propiconazole, azaconazole, imazalil; heterocyclic compounds, e.g. 2-methyl-3(2I-,I -isothiazolone, 5-chloro-2-methyl-3(2H)-isothiazolone, 2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-(n-octyl)-4-isothiazolin=3-one,1,2-benzisothiazolin-3-one, 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, 2-(4-thiazolyl)-benzimidazole, 2-mercaptobenzothiazole, 2-(thiocyanomethylthio)benzthiazole; N-haloalkylthio compounds, e.g. N-trichloromethylthiophthalimide, folpet, N-trichloromethylthio=4-cyclohexane-1,2-dicarboximide, captan, N-1,1,2,2-tetrachloroethylthio-4-cyclohexene-1,2-dicarboximide, captafol, dichlofluanide, t.olylfluanide; compounds with activated halogen groups, e.g. chlorothalonil; surface active agents, e.g. guanidines and biguanides; organometallic compounds, e.g. bis(tri-n-butyltin-oxide, tributyltin esters, tributyltin naphthenate, tributyltin linoleate, tributyltin benzoate, tributyltin fluoride;
various compounds, e.g. pimaricine, tridemorph, methylene bisthiocyanate, tolyl -sulfone, dicyanobutane; metal salts, e.g. chrome-eopper-ai-senic; active natural products, e.g. streptomycin; auxiliary solvents such as ethylglycol acetate and methoxypropylacetate; processing additives; fixatives 'such as carboxymethyl-cellulose, polyvinyl alcohol, paraffin ; plasticizers such as benzoic acid esters and phthalates, e.g.
dibutyl phthalate, dioctyl phthalate, diuodecyl phthalate; UV-stabilizers- or stability enhancers; dyes; color pigments; siccatives such as cobalt octoate, lead octoate and cobalt naphthenate; corrosion inhibitors; antisettling agents; anti-skinning agents such as methyl ethyl ketoxime; antifoaming agents and the like. Generally, the adjuvants are not essential to the practice of the present invention but are included in particular formulations, especially in coating formulations to optimize overall effectiveness and ease of application. They can be used therein in the conventional amounts.

The antibacterial and/or antifouling compositions which are employed in the method of .
the invention can contain from 0.001% to 95% of the active ingredient by weight based on the total weight of the composition. Ready-to-use compositions such as paints preferably contain from 0.5% to 20%, in particular from 1 to 10% by weight of the active ingredient. Antifouling paint compositions on the other hand can contain from 1%
up to 75%, in particular from 20 to 70% of the active ingredient of formula (I) by weight, based on the total weight of the dry mass of'said composition (i.e. up to 50%, in particular from 5 to 25% of the active ictgredient by weight based on the total weight of the antifouling composition). Preferred compositions are composed in particular of the following constituents (all percentages are by weight) :
Emulsifiable concentra.tes active ingredient : 1 to 20%, preferably 5 to 10%
surfactant : 5 to 30%, preferably 10 to 20% ..
liquid carrier : 50 to 94%, preferably 70 to 85%
Dusts active ingr.edient := 0.1 to 10%, preferably 0.1 to 1%
solid carrier : 99.9 to 90%, preferably 99.9 to 99%
. Suspension concentrates active ingredient : 5 to 75%; preferably . 10 to 50%
water : 94 to 25%, preferably 88 to 30%
surfactant : 1 to 40%, preferably 2 to 30%
nulates .
active ingredient 0.5 to 30%, preferably 3 to 15%
-solid carrier : 99.5 to 70%, preferably 97 to 85%

The following examples are not intended to limit, but to illustrate the scope of the invention.

A. Biological Examples Example 1: Efficacy against Bacteria and Yeasts.
Test solutions were prepared by dissolving the compourids shown in Tables 1-4 in 50% ethanol and further diluting with, sterile distilled water. These test solutions were pipetted into Petri dishes and mixed with warm tryptose agar to reach an active ingredient concentration of 100 ppm. After cooling, the medium was inoculated with the following yeasts or bacteria :
Debaryomyces hansenii (yeast) (A) Pseudomonas alcaligenes (gram neg) (B) Bacillus cereus mycoides (gram pos) (C) Pseudomonas aeruginosa (gram neg) (D) Flavobacterium sp. (gram neg) (E) Streptomyces albus (gram pos) (F) Enterobacter aerogenes (gram neg) (G) Escherichia c"oli (gram neg) (H) After sufficient growth of the untreated cultures, the compounds were evaluated using the following rating system :

0 = growth equal to control.
1 = inhibition of growth by the compound.
2= no growth under the influence of the compound.
The scores measured for antibacterial and antifouling efficacy of the compounds of this invention are listed in Tables 1-4. The sign '- signifies the; compound was not tested.
Table 1 ~s R

[ala Compounds Bacteria Co. no. n R A B C D E F G H
1 1 4-chlorophenyl 2 -1 2 0 2 2 0 2 2 2 2,4-dichlorophenyl 2 0 2 0 2 0 0 0 3 1 3-nitro hen- 1 2 2 2. 1 2 2 1 2 Com ounds Bacteria 4 1 3,4-dichlorophenyl 2 1 2 0 2 2 0 2 2 2-methylphenyl 2 0 2 0 2 2 0 1.
6 1 3-fluorophenyl 2 1 2 0 2 2 0 2 7 1 2-furanyl 2 1 2 0 2 0 0 0 8 1 2-thienyl 2 2 2 1 2 2 2 2 9 1 3-methoxyphenyl 0 0 0 0 0 0 0 0 1 4-methylphenyl 2 1 2 1 2 2 0 2 11 2 4-methylphenyl 2 1 1 1 2 1 0 0 12 2 2-furanyl 0 0 0 0 0 0 0 0 13 1 3-trifluoromethyl 2 0 2 0 2 2 0 2 phenyl 14 1 4-ethanonephenyl 2 1 2 1 2 2 0 2 1 2,6-dichlorophenyl 1 0 1 0 0 0 0 0 16 2 2,6-dichlorophenyl 2 0 2 0 0 0 0 0 17 2 phenyl 0 0. 0 0 0 0 0 0 18 2 4-chlorophenyl - 1 2 0 2 2 0 0 19 2 3,5-dichlorophenyl - 0 2 0 2 2 0 0 1 4-butoxyphenyl 0 0 0 0 0 0 0 0 21 1 3,5-dichlorophenyl - 2 2 0 2 2 0 0 22 1 4-benzoic acid - 1 0 0 2 2 0 0 ethyl ester 23 2 3-chlorophenyl 0 . 0 0 0 0 0 0 0 24 2 4-trifluoromethyl - 0 2 0 2 2 2 0 phenyl 1 4-trifluoromethyl - 1 2 0 2 2 0 0 phenyl 26 . 1 3-benzoic acid, - 0 2 0 2 2. 0 0 methyl ester 27 2 3-bromophenyl - 1 2 0 2 2 0 2 28 1 4-ethoxyphenyl - 0 0 0 2 2 0 0 Table 2 R~ 'N
f [0'ln Co. No. Rl R2 R3 R4 X n M.P. ( C) 32 H CH3 H H S 0 oil 35 H H H Br S 0 82-83 36 H H H Br S 1 113414 38 H H H Br S 2 118-119 40 H H Br H S 0 74-75 41 H H Br . H S 1 169-173 42 H H Br H . . S 2 126-127 44 H . HCU2CH3 CH3 0 1 . 147-148 45 ' H H CH3 CO2CH3 S 1 150-152 .48 H H H CH3 S 1109-111 52 CH3 H H H S '0 70-72 53 H H. H CO2CH2CH3 S 0 68-69 56 H H H _ CN S 0 136-137 Co. No. R1 R2 R3 R4 X n M.P. ( C) 59 . H H H Cl S 0 74-77 60 H .H H C1 S 1 102 61 . H H H CI S 2 113-114 63 H H H NO2 S. 0 162-163 66 H H H CH=NOCH3 S 2 168-170 67 H -H H . C6H5 S 0 100-103 68' H H H C6H5 S 1 144-147 69 H H H . C6H5 S 2 95-98 71 H H CH3 Br S 0 oil 72 H H CH3 Br S 1 100-104 73 H H Br CH3 S 0 64-67.

Table 2a ~-N R2 ~
S
[0]n S

Co. No. R2 n M.P. ( C) Table 3. . ..
O, N

S X
[O Y
l a Co. No. R" X Y n M.P.( C) 91 H S GOCH(CH )2 1 ozl Table 4 oeN
Rlo Co1õ R

R$

Co. No. R8 R9 R10 M,.P.( C

93 . H F H 1 132-133 96 F F . H. 0 63-65 - -- - --------Co. No. R8 R9 R 10 n M.P. ( .C) 103 CO2CH(CH3)2 Cl H 0 oil 104 CO2CH(CH3)2 Cl H 1 127-129 105 CO2CH(CH3)2 Cl n 2 82-83 106 H CH=NOCH3 H 1 85-87 107 H ICH=NOCH31 H 2 104-106 Exainple 2: Efficacy against Fresh-water algae 9 ml of Bold's algal broth containing an appropriate concentration of test compound, was inoculated in a 5.5 cm diameter plastic Petri dish with 1 ml of a two week old stock culture of one of three species of green algae (Chlamydomonas dysosmos, Chlorella vulgaris or Ulothrix ca,~'ervicola) or the blue-green bacterium Anabaena cylindrica. The dishes were incubated in a climate room under a photosynthetically active radiation level of 40 mole.m-2.sec-1 at 20 C during the day (16 h) and 18 C at night (8 h).
Evaluation was performed after 14 days by visually estimating the percentage- of algal growth as compared to controls. Results are expressed as minimum test concentration (in ppm) giving 90% mortality.

Com. ounds Concentration (ppm) Co. nQ. n R Chiamydomonas Chlotella Ulothrix Anabaena dysosmos vulgaris confervicola cylindrica 4 1 3,4-dichlorophenyl 2.5 10 2.5 2.5 8 1 2-thienyl 2.5 5 1 2.5.
18 2 4-chlorophenyl 2.5 10 5 2.5 19 2 3,5-dichlorophenyl 5 -10 2.5 2.5 21 1 3,5-dichiorophenyl 1 5 1 2.5 25 1 4-trifluoromethyl 2.5 10 2.5 5 hen. l Ex=le 3: Efficacy against Marine algae 9 ml of Provasoli A8P-2 (Artificial Seawater-2) medium containing an appropriate concentration of test compound, was inoculated in a 5.5 cm diameter plastic Petn dish with 1 ml of a two weeks old stock culture of the diatom Phaeodactylurn tricornutwn or the unicellar red alga Porphyridiurn sp. The dishes were incubated in a clirnate room under a photosynthetically active radiation level of 40 mole.m-2.sec-1 at 20 C during the day (16 h) and 18 C at night (8 h). Evaluation was performed after 14 days by visually estimating the percentage of algal growth as compared to controls.
Compounds 1, 2, 3, 4, 5, 14, 15, 16, 18, 19, 21, 25, 27 caused 90% mortality at concentration levels equal to or lower than 1 ppm.
Example 4: Efficacy against Artemia Into 1 ml of artificial sea-water containing different amounts of the test compound, approximately 15 Artemia Instar II larvae were added. After 24 hours of static incubation with continuous illumination the test was evaluated.
Compounds 2, 4, 5; 11, 13, 18, 19 caused 100% mortality at concentration levels equal to or lower than 10 ppm.

B. Composition examples (all percentages.are by weight) Example 5: Composition examples for solid compounds of formula (I) a) Emulsifiable concentrates : emulsions of any concentration could be obtained from these concentrates by dilution with water.
a) b) compound of formula (1) 10% 1%
octylphenol polyethylene glycol ether (4-5 moles of ethylene oxide) 3% 3%
calcium dodecylbenzenesulfonate 3% 3%
castor oil polyglycol ether (36 moles of ethylene oxide) 4% 4%
cyclohexanone 30% 10%
diniethylbenzene mixture 50% 79%

b) Dusts were obtained by mixing the active ingredient with the carriers, and grind.ing the mixture in a suitable mill. a) b) compound of formula (1) 0.1% 1%
talcum 99.9% -kaolin - 99%

c) Suspension concentrates from which suspensions of any desired concentration could , be obtained by dilution with water were obtained by intimately mixing finely ground .
active ingredient with the adjuvants. a) b) compound of formula (I) 40% 5%
ethylene glycol 10% 10%
nonylphenol polyethylene glycol ether = i (15 moles of ethylene oxide) 6% 1%
sodium lignosulfate 10% 5%
carboxymethylcellulose 1% 1%
37% aqueous formaldehyde solution 0.2% 0.2%
silicone oil in the form of a 75%
aqueous emulsion 0.8% 0.8%
water 32% 77%
Ex le 6 Composition examples for liquid active ingredients of formula (I) a) Emulsifiable concentrates : emulsions of any concentration could be obtained from these concentrates by dilution.with water.
a) b) . c) compound of formula (I) 20% 40% 50%
calcium dodecylbenzenesulfonate 5% 8% 5.8%
castor oil polyethylene glycoi ether (36 moles of ethylene oxide) 5% - -tributylphenol polyethylene glycol ether (30 moles of ethylene oxide) .12% 4.2%
cyclohexanone - 1.5% 20%
dimethylbenzene mixture 70% 25% 20%
b) Solutions suitable for application in the form of microdrops.
a) b) c) d) compounds of fornlula (I) 80% 10% 5% 95 k ethylene glycol monoethyl ether 20% - - -polyethylene glycol (1VIG 400) - 70% - -~T-methyl-2-pyrrolidone - 20% - -epoxidised coconut oil - - 1% 5%
petroleum distillate (boiling range 160-190- C) - . - 94%

c) Granulates : prepared by dissolving the active ingredient in.
dichloromethane, spraying the solution onto the carrier, and subsequently evaporating the solvent.
a) b) compound of formula (I) 5% 10%
kaolin 94% -highly dispersed silicic acid 1%
attapulgim . - . 90%

d) Dusts : were obtained by intimately mixing the carriers with the active ingredient.
a) b) compound of formula (I) 2% 5%
highly dispersed silicic acid 1% 5%
talcum 97% -kaolin - 90%

Example 7: Composition examples for paints a) Compound of formula (I) 6.0 %
Titanium dioxide 17.1 %
Whiting 9.7%
Talc 13.2%
Calgon , 0.1 %
Hydroxyethylcellulose (3% solution in water) 12.5%
Co-solvent 1.2 %
Minor additives 0.4 %
Water 27.7%
Vinyl acetatefversatate copolymer emulsion 12.1 %

b) Compound of formula (I) 1.0 %
Titanium dioxide 26.4 %
Soya alkyd resin 44.0%
White spirit . 27.5 %
Cobalt octoate (8%) 0.3 %
Lead octoate (33%). 0.7 %
Methyl ethyl ketoxime 0.1 %

Claims (6)

Claims

1. A coating composition comprising (a) as active ingredient a compound having the formula wherein n is 0, 1 or 2; R1 is hydrogen, C1-4alkyl or benzyl; and R represents (i) phenyl; phenyl substituted with 1 to 3 substituents independently selected from hydroxyl, halo, C1-12alkyl, C5-6cycloalkyl, trihalomethyl, phenyl, C1-5alkoxy, C1-5alkylthio, tetrahydropyranyloxy, phenoxy, C1-4alkylcarbonyl, phenylcarbonyl, C1-4alkylsulfinyl, C1-4alkylsulfonyl, carboxy or its alkali metal salt, C1-4alkyloxycarbonyl, C1-4alkylaminocarbonyl, phenylaminocarbonyl, tolylaminocarbonyl, morpholinocarbonyl, amino, nitro, cyano, dioxolanyl or C1-4alkyloxyiminomethyl; naphthyl; pyridinyl; thienyl;
furanyl; or thienyl or furanyl substituted with one to three substituents independently selected from C1-4alkyl, C1-4alkyloxy, C1-4alkylthio, halo, cyano, formyl, acetyl, benzoyl, nitro, C1-4alkyloxycarbonyl, phenyl, phenylaminocarbonyl and C1-4alkyloxyiminomethyl; or R represents a radical of formula wherein X is oxygen or sulfur; Y is nitrogen, CH or C(C1-4alkyloxy); and R"
is hydrogen or C1-4alkyl, and (b) polymers or copolymers derived from monomers or resins.

2. The coating composition of claim 1, wherein when R represents thienyl, n is not 2.

3. The coating composition of claim 1, wherein the polymers or copolymers are derived from dialkyl siloxane monomers, (meth)acrylic acid monomers, (meth)acrylic acid ester monomers, vinyl and allyl alcohol monomers, vinyl and allyl ester monomers, maleic acid monomers, styrene monomers, vinylchloride monomers, butadiene monomers, acrylamide monomers, acrylonitrile monomers, alkyd resins, polyurethanes, epoxy resins, phenolic resins or urea-formaldehyde resins.

4. The coating composition according to any one of claims 1 to 3 further comprising one or more additives selected from the group consisting of water-repelling agents;
surface slipping agents; organic binding agents; insecticides; fungicides;
bactericides;
auxiliary solvents; processing additives; fixatives; plasticizers; UV-stabilizers or stability enhancers; dyes; color pigments; siccatives; corrosion inhibitors;
antisettling agents; anti-skinning agents; and antifoaming agents.

5. An antifouling paint composition comprising the composition as defined in any one of claims 1 to 3 comprising from 10% up to 75% by weight of the active ingredient based on the total weight of the dry mass of said antifouling paint composition.

6. The coating composition according to any one of claims 1 to 3 wherein the compound of formula (I) is 5,6-dihydro-3-(2-thienyl)-1,4,2-oxathiazine-4-oxide; 3-(4-chlorophenyl)-5,6-dihydro-1,4,2-oxathiazine-4,4-dioxide; or 3-(benza[b]thien-2-yl)-5,6-dihydro-1,4,2-oxathiazine-4-oxide.