CA2021496A1

CA2021496A1 - Composition, process and use

Info

Publication number: CA2021496A1
Application number: CA002021496A
Authority: CA
Inventors: Mark R. James; Gordon A. Thomson
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Syngenta Ltd
Priority date: 1989-07-19
Filing date: 1990-07-19
Publication date: 1991-01-20
Also published as: PT94760B; US5393750A; ES2124213T3; JPH0368553A; DE69032752T2; PT94760A; NZ234584A; ATE173248T1; IE902650A1; NO903231L; EP0409617A3; GB8916447D0; NO180403C; GB9015891D0; ZA905703B; NO903231D0; EP0409617B1; FI101295B; US5120856A; AU629014B2

Abstract

ABSTRACT
COMPOSITION, PROCESS AND USE
A compound of the general formula

Description

292~

-Composition, Process and Use The present invention relates to a class of compound, a process for the preparation of such compounds and the use of such compounds as industrial biocides.

IndustriaL biocides are useful to prevent industrial spoilage, in particular that caused by bacteria, fungi and algae.
Materials which can be used as industrial biocides have antimicrobial properties, for example antifungal, antibacterial or antialgal properties and may even pO88eS8 2 combination of properties such as both useful antifungal and antibacterial properties. Such materials are useful in t'ne preservation of products which are susceptible to attack by micro-organisms such as bacteria, fungi and algae. A wide range of products are susceptible to attack by micro-organisms and these products include paints, latices, adhesives, personal care products, leather, wood, plastics materials and additives to plastics materials, metal working fluids, cooling water and aqueous slurries.

In our European Patent Application Publication No 249328 we disclose a biocide composition which contains at least one compound of the formula A \

/ N - OR
B
C = S

or a metal complex or salt thereof, the groups A, B and D being defined. Many compounds of this type are disclosed. The specific compounds disclosed are of the type thiazol-thione, imidazolidine-thione or imidazoline-thione. We have now found that compounds of the type pyrrolidine thione derivatives and pyrroline thione derivatives have useful anti-microbial properties.

-2- S 35357 According to the present invention tnere is provided a biocide composition which contains at least one compound of the formula I:-~X
Y N - OR
I \
\ ~C - S
z or a salt or complex thereof, wherein X is a group -CRlR2- or a group -CRl =;
Y is a group -CR3R4- or a group -CR3 =;
Z is a group -CR5R6- or a group -CR5 -;
R is hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -CooR7;
Rl to R6 are each, independently, a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group, or 1 5 Rl and R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or Rl and R3, together with the carbon atoms to which they are attached, form a ring or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group.

-3- S 35357 The groups X, Y and Z can form part of a further ring system but generally not more than two of the groups X, Y and Z form part of a further ring system. ThP further ring system is typically a ring system containing five or six atoms and may be ~ heterocyclic ring system but is preferably a hydrocarbon ring system, for example a cyclopentene, cyclohexane, cyclohexene, cyclohexadiene or benzene ring. The further ring system, if present, typically contains one or two carbon atoms from the groups X, Y, and Z. If only one group forms part of a ring system, this may be a cyclohexane ring of the type ~ CH2 ~ CHz "~

~ CH2 _ CH~

where the carbon atom of the group X, Y or Z is the carbon atom with the two free valencies, which are linked to the other groups in the pyrrolidine or pyrroline ring. If two of the groups X, Y and Z form part of a ring system, the further ring is then fused to the pyrrolidine or pyrroline ring system; for example when Y and Z both form part of a ring system such as a benzene rin~ as in 2-hydroxy-2,3-dihydro-lH-isoindol-1-thione.

Particularly useful biocide compositions in accordance with the present invention are those in which the group X is a group -CRlR2-, and especially is a group CH2- or -C(CH3)2-. The groups Y
and Z may be groups -CR3R4- or -CR3S and -CR5R5- or -CR5=
respectively. We have obtained useful biocide compositions using a compound in which the groups Y and Z are both -CH2- groups. Useful results have also been obtained when the compound is one in which X
is -CH2- and Y and Z together form a benzene ring.

If any of the groups Rl to R6 are substituted groups, the substituents are typically selected from hydrocarbonoxy groups, acyl groups, ester (that is acyloxy) groups, a halogen atom or a group containing more than one halogen atom, for example a trifluoromethyl group, or a nitrile group.

-4- S 35357 The group R may be an acyl group, for example an acetyl group (CH3C0). However, it is generally preferred that the biocide composition contains a salt or complex of the compound of general formula I. The salt or complex may be with an amine (including an alkanolamine) but more typically is with a metal, which may be any metal. Typically the metal present in the salt or complex is a transition metal, for example a metal of group VIII, IB or IIB of the Periodic Table. Such metals include iron, copper and zinc, particularly such metals in their maximum possible valency state.

All references herein to the Periodic Table are to the Periodic Table according to Mendeleeff, as set out on the inside rear cover of "~eneral and Inorganic Chemistry~ by J R Partington, Second Edition (1954) published by MacMillan and Co Limited, London.

For convenience hereafter, the compounds of the general formula I, and the salts and comple~es thereof will be referred to simply as "compound I".

A wide range of compounds I can be used in the biocide compositions of the present invention. The compounds I have anti-microbial activity against a wide range of micro-organisms including bacteria, fungi and algae, and have useful anti-bacterial activity. Preferred compounds I have a useful combination of anti-bacte~ial, anti-fungal and anti-algal activity.

Compounds I which can be used in the compositions of the present invention include:
1-acetoxy-2-pyrrolidinthione;
l-acetoxy-5,5-dimethyl-2-pyrrolidinthione; and 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione.
and the metal complexes and salts thereof. The metal salts and complexes thereof include ferric, cupric and zinc complexes and salts. Compositions of the present invention which contain metal salts or complexes are preferred, for example compositions which contain one of the following complexes:-

-5- S 35357 2:1 complex of 2-hydroxy-~,3-dihydro-lH-isoindol-1-thione and zinc;
2:1 complex of 1-hydroxy-2-pyrrolidinthione and zinc; and 2:1 complex of 5,5-dimethyl-1-hydroxy-2-pyrrolidinthione and zinc.

The biocide composition of the present invention includes a carrier in addition to compound I. The carrier is typically a material which shows little, if any, antimicrobial activity and may be, or may include, a material which is susceptible to the growth of micro-organisms.

It is generally preferred that the carrier is a liquid medium and the biocide composition may be a solution, suspension or emulsion of compound I in a liquid carrier. The carrier may be water, in which a number of compounds of formula I, OL' the salts or complexes thereof, are essentially insoluble. Alternatively , the carrier may be a liquid such as acetic acid, N,N-dimethylformamide, propylene glycol, dimethyl sulphoxide or N-methyl-2-pyrrolidone in which many compounds of formula I, or the salts or complexes thereof, are soluble. Alternatively, a mixture of liquids may be used, one being a solvent for compound I and the other being a non-solvent, and using such a mixture the composition typically comprises an emulsion or droplets of a solution of compound I in the solvent therefore dispersed in the non-solvent. If a suspension or emulsion is used, this conveniently contains a surface active agent which is effective to maintain the non-continuous phase as a suspension or emulsion.
Any surface active agent known for use in biocide compositions may be used in such a system, for example alkylene oxide adducts of fatty alcohols, alkyl phenols and amines such as ethylene diamine.

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-6- S 35357 The carrier may be alternatively be a solid when the biocide co~position is very conveniently a solid, particulate material. The solid carrier may be a water-insoluble carrier such as silica or alumina. However, for ease of dispersion into a medium to be treated, it is preferred that the carrier is a water-soluble material since many of the media to be treated are aqueous systems.
Any water soluble material may be used as a carrier provlded it does not react with, and adversely affect, the antimicrobial properties of compound I. One class of carrier which may be used in the water-soluble inorganic salts, particularly salt of monovalent metals especially the alkali metals. Compound I may be deposited onto the carrier using any known technique for depositing a material from solution onto a solid.

The amount of compound I which is present in the biocide composition may be just sufficient to have an antimicrobial effect or compound I may be present in a substantially greater proportion. It will be appreciated that the biocide composition may be provided as a concentrated solution which is subsequently diluted for use as an anti-microbial material. Thus, the amount of the compound I which is present in the biocide composition is typically in the range from 0.0001% up to 50~ by weight of the biocide composition.

Some of the compounds used in the biocide composition of the present invention are new.

Thus,as a further aspect of the present invention there is provided a compound of the formula , Xl yl ~ N - OR

zl ~2~

-7- S 35357 wherein:-xl is a group -CRlR2- or a group -CRl=;
yl is a group -CR3R4- or a group -CR3=;
zl is a group -CR5R6- or a group -CR5=, and R and Rl to R6 are all as herein before defined, with the exceptions that when Xl is -C(CH3)2-, R is -H or -CH3 and yl is -CH2-, zl is neither -CH2- nor -C(CH3)2-; and when Xl is -C(CH3)2-, R is -H or -CH3 and zl is -CH2-, yl is neither -CH(CH3)- nor -CH(C6H5)-.

Preferred compounds in accordance with this further aspect of the present invention are those in which the group Xl.is a group -CRlR2- and especially is a group -CH2-, subject to the exceptions as herein before defined.

As a yet further aspect of the present invention there is provided a salt. or complex of a compound of the formula ,~X~, Y N - OR

\ _ C = S
z where R, X, Y and Z are all as hereinbefore defined.

In the compounds according to the yet further aspect of the - 20 present invention, it is preferred that the group X is a group -CRlR3 and especially is a group -C~l2- or a group -C(CH3)2-.

The salt or complex is especially one with a metal and materials having useful properties have been obtained in which the metal is zinc. Thus, particular materials in accordance with this aspect of the pres0nt inventlon are the salt or complex of 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione and zinc; the salt or complex Df 1-hydroxy-2-pyrrolidinthione and zinc and the salt or complex of 5,5-dimethyl-1-hydroxy-2-pyrrolidinthione and zinc.

-8- S 35357 Compounds of formula I may be prepared in a multi-stage procedure starting from 1,2 dialdehydes, and the product thus obtained may be further reacted to obtain a salt or complex if desired. More specifically, a dialdehyde is reacted with hydroxylamine to obtain a N-hydroxypyrrolidone or pyrrolinone derivative as an intermediate product. The intermediate product is treated with an acid nalide such as acetyl chloride to esterify th0 N-hydroxy group, the esterified product is treated with Lawesson's reagent to obtain the acetyl thione. This acetyl derivative, which is a compound of formula I, is preferably hydrolysed to obtain a hydroxythione compound of formula I. A salt or complex is then obtained, if desired, by reaction with a metal salt, for example zinc acetate.

We have found that some hydroxythione compounds of formula 1 5 I, that is compounds in which R is hydrogen, are somewhat unstable and may be difficult to isolate in ~ satisfactory yield. We have found that the desired salt or complex may be obtained directly from the acyl derivative by reaction with a trialkylsilanolate of the desired metal.

Thus, as a further feature of the present invention there is provided a process for preparing a metal salt or metal complex of a compound of formula I, wherein a trialkylsilanolate of the metal is reacted with a compound of formula I in which the group R is an acyl group.

The trialkylsilanolate is conveniently a trimethyl-silanolate. The metal is conveniently æinc. The reaction is conveniently effected in the presence of a liquid medium which is a solvent for one or both of the reactants but which is preferably a non-solvent, or a poor solvent, for the desired metal salt or metal complex. A suitable liquid medium is tetrahydrofuran but other liquids such as diethyl ether, 1,4-dioxane, toluene, benzene or other aprotic liquids may be used as the liquid medium. The reaction is conveniently effected at ambient temperature or below, for example at 0C. The reaction is preferably carried out in the essential absence of moisture for example using dry air or in an inert gaseous atmosphere such as nitrogen or argon.

~2~
~9_ S 35357 The reaction product is convenient]y insoluble in the reaction medium and forms a precipitate which can be isolated by any suitable means, for example by filtration. The process requires only a single stage and generally gives a higher yield of the metal salt or metal complex than is obtained by hydrolysis to form the hydroxy derivative followed by reaction to obtain the metal salt or metal complex.

As an alternative to using butanedial, a 1,2-dialdehyde, as a starting material to obtain l-hydroxy-2-pyrrolidinone, we have prepared this compound from cyclobutanone. More specifically, cyclobutanone is reacted with N-hydroxybenzenesulphonamide in the presence of a base in a suitable liquid medium. The mixture is acidified to recover the desired hydroxy compound. The reaction is conveniently effected at ambient temperature or below, for example at an initial temperature of -10C and allowing to warm up to ambient temperature. Any suitable liquid medium may be used and we have obtained satisfactory results using aqueous ethanol as the liquid medium.

A convenient process for the preparation of a metal salt or metal complex of a compound of formula I comprises the steps of l) reacting a l-hydroxy-2-pyrrolidinone or l-hydroxy-2-pyrrolinone derivative with an acid halide; and 2) reacting the product of step l with Lawesson's reagent.

The product of step 2 in the foregoing process is a l-acyloxy-2-pyrrolidinthione compound of formula I. This may be the desired product but generally it is preferred that the ~inal product is a salt or complex of a compound of formula I. Such a product may be obtained by hydrolysis of the acyloxy compound to obtain the corresponding hydroxy compound and reacting this hydroxy compound with a salt, particularly a metal salt, to obtain the desired salt or complex. However, as noted previously herein, a salt or complex can be obtained by reacting the acyloxy compound with a metal trialkylsilanolate and we generally prefer to prepare a metal salt or metal complex of the compound of formula I by reaction of the acyloxy compound with a metal trialkylsilanolate.

~ ~ ~ (J ~

~ompound I, typically has anti-bacterial, anti-fungal and anti-aLgal activity and preferred Compounds I have useful anti-bacterial, anti-fungal and anti-algal activity. Hence, compound I, or biocide compositions containing compound I, can be used for the treatment of various media to inhibit the growth of micro-organisms.

As a further aspect of the present invention there is provided a method for inhibiting the growth of micro-organisms on, or in, a medium which comprises treating the medium with compound I or a biocide co~position containing compound I.

Compound I or the biocide composition can be used in conditions in which micro-organisms, especially fungi, bacteria and/or algae, grow and cause problems. Systems in which micro-organisms cause problems include liquid, particularly aqueous, systems such as cooling water liquors, metal working fluids, ,5 geological drilling lubricants, polymer emulsions and surface coating compositions such as paints, varnishes and lacquers and also solid materials such as wood and leather. Compound I or the biocide composition can be included in such materials and is particularly useful when incorporated into a paint, varnish or lacquer to which they provide anti-microbial characteristics.

As a particular aspect of the present invention there is provided a surface coating composition which contains an effective amount of compound I

The surface coating composition may be a paint, varnish or lacquer and is especially a paint, for example an emulsion paint.
The amount of compound I which is present in the surface coating composition is typically in the range from 0.001 up to 2% by weight and especially 0.1 up to 1% by weight relative to the total weight of the surface coating composition. Compound I can provide a range of anti-microbial characteristics, for example anti-fungal properties, and also anti-algal properties, to the surface coating composition when applied to a surface and can also provide anti-bacterial properties which are useful for in-can preservation of the surface coating composition.

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~ S 35357 Compound I may be the only antimicrobial compound or may be used in a biocide composition which includes other compounds having antimicrobial characteristics. Thus, a mixture of different compounds of ~ormula I, or salts or complexes thereof, may be used.
Alternatively, at least one compound of the formula I, or a salt or complex thereof, may be used together with one or more known antimlcrobisl compounds. The use of a mixture of anti-microbial compounds can provide a composition having a broader anti-microbial spectrum and hence one which is more generally effective than the components thereof. The known anti-microbial may be one pcssessing anti-bacterial, anti-fungal, anti-algal or other anti-microbial chsracteristics. The mixture of compound I with other anti-microbial compounds typically contains from 1 to 99~ by weight, relative to the weight o total antimicrobially active compounds, of Compound I
particularly from 40 to 60~ by weight of Compound I.

As examples of known antimicrobial compounds which may be used, together with Compound I, there may be mentioned quarternary ammonium compounds such as diethyldodecylbenzyl ammonium chloride;
dimethyloctadecyl-(dimethylbenzyl)ammonium chloride;
dimethyldidecy:Lammonium chloride; dimethyldidodecylammonium chloride; trimethyl-tetradecylammonium chloride;
benzyldimethyl(C12-C18 alkyl)ammonium chloride;
dichchlorobenzyldimethyldodecylammonium chloride;
hexadecylpyridinium chloride; hexadecylpyridinium bromide;
hexadecyltrimethylammonium bromide; dodecylpyridinium chloride;
dodecylpyridinium bisulphate; benzyldodecyl-bistbeta-hydroxyethyl)-ammonium chloride dodecyl-benzyltrimethylammonium chloride;
benzyldimethyl(C12-C18 alkyl)ammonium chloride;
dodecyldimethylethyl ammonium ethylsulphate; dodecyldimethyl-(l-naphthylmethyl)ammonium chloride; hexadecyl-dimethylbenzyl ammonium chloride; dodecyldimethylbenzyl ammonium chloride and 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamatane chloride; urea derivatives such as 1,2-bis(hydroxymethyl)-5,5-dimethylhydantoin; bis(hydroxymethyl)urea; tetrakis(hydroxy-methyl)scetylene diurea; 1-(hydroxymethyl)~5,5-dimethylhydantoin and ~2~ s~

imidazolidinyl urea; amino compounds such as 1,3-bis(2-ethyl-hexyl;-5-methyl-S-aminohexahydropyrimidine; hexamethylene tetra amine;
1,3-bis(l~-aminophenoxy)propane; and 2-[(hydroxymethyl)-amino]ethanol; imidazole derivatives such as 1[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-lH-imidazole;
2-(methoxycarbonyl-amino)-benzimidazole; nitrile compounds such as 2,4,5,6-tetra-chloroisophthalodinitrile and 1,2-dibromo-2,4-dicyanobutane; thiocyanate derivatives such as methylene bis thiocyanate: zinc compounds or complexes such as zinc-2-pyridinethiol-N-oxide; tin compounds or complexes such as tributyltin-oxide, chloride, naphthoate, b~nzoate or 2-hydroxybenzoate: thiazole derivatives such as 2-(thiocyano-methylthio)-benzthiazole; and mercaptobenzthiazole; isothiazole-derivatives such as 5-chloro-2-methyl-4-isothiazolin-3-one and magnesium salts thereof; 2-methyl-4-isothiazolin-3-one;
1,2-benzisothiazolin-3-one and the alkali metal, ammonium and amine salts thereof; and 2-n-octyl-4-isothiazolin-3-one; nitro compounds such as tris(hydroxymethyl)nitromethane, 5-bromo-S-nitro-1,3-dioxane and 2-bromo-2-nitropropane-1,3-diol; aldehydes and derivatives such as gluteraldehyde (pentanedial) p-chlorophenyl-3-iodopropargyl formaldehyde and glyoxal; amides such as chloracetamide, N,N-bis(hydroxymethyl)chloracetamide, N-hydroxymethyl-chloracetamide and dithio-2,2-bis(benzmethyl amide); guanidine derivatives such as poly hexamethylene biguanide and 1,6-hexamethylene-bis[5-(4-chlorophenyl)biguanide]; thiones such as 3,5-dimethyltetrahydro-1,3,5-2H-thiodiazine-2-thione; triazine derivatives such as hexahydrotriazine and l,3,5-tri-(hydroxyethyl)-1,3,5-hexahydrotriazine; oxazolidine and derivatives thereof such as bis-oxazolidine; furan and derivatives thereof such as 2,5-dihydro-2,5-dialkoxy-2,5-dialkylfuran; carboxylic acids and the salts and esters thereof such as sorbic acid and the salts thereof and 4-hydroxybenzoic acid and the salts and esters thereof; phenol and derivatives thereof such as 5-chloro-2-(2,4-dichlorophenoxy) phenol, thio-bis(4-chlorophenol) and 2-phenylphenol; sulphone derivatives such as diiodomethyl-paratolyl sulphone, 2,3,5 6-tetrachloro-4 (methylsulphonyl) pyridine and hexachlorodimethyl sulphone.

Compound I is particularly useful when incorporated into a surface coating composition and hence, if used with other compounds having antimicrobial characteristics, these other compounds are advantageously compounds of the type used in surface coatlng compositions. Compounds which may be used in surface coating compositions include, inter-alia, anti-bacterial agents such as imidazolidinyl urea; 1, 2-dibromo-2,4-dicyanobutane:
5-chloro-2-methyl-4-isothiazolin-3-one and the magensium salts thereof; 2-methyl-4-isothia~olin-3-one; 1,2-benzisothiazolin-3-one and the salts thereof; 2-bromo-2-nitropropane-1, 3-diol;
gluteraldehyde; poly hexamethylene biguanide; triazine derivatives and oxazolidine and derivatives thereof. Surface coating compositions may also include anti-fungal agents such as 1[2-(2, 4-dichlorophenyl)-2-(2-propenyloxy) ethyl]-lH-imldazole;
2-(methoxycarbonylamino)-benzimidazole; 2,4,5,6-tetrachloro-isophthalodinitrile; zinc-2-pyridinethiol-N-oxide;
2-(thiocyanomethylthio)-benzthiazole; 2-n-octyl-4-thiazolin-3-one;
dithio-2, 2-bis (ben~methyl amide); diiodomethyl-paratolysulphone and 2,3,5,6-tetrachloro-4 (methylsulphonyl) pyridine.

Further aspects of the present invention are described in the following illustrative examples. In the following tests and examples, all parts are by weight unless stated to the contrary.

In the following examples, the products obtained were subjected to microbiostatic evaluation. The microbiological testing was e~fected, under sterile conditions throughout, as follows:

In the microbiological testing, the products were tested for anti-microbial activity against bacteria and fungi. The bacteria used were one or more of Escherichia coli, Pseudomonas seruginosa, Staphylococcus aureus and Bacillus subtiles. The fungi used were one or more of Alternaria alterna~a, Aspergillus niger, Aureobasidum pullulans, Cladosporium sphaerospermum, Cladosporium herbarum, Penicillium pinophilum, Gliocladium roseum and Chaetomium globosum.
Testing against the yeast, candida albicans was also carried out in some cases. Anti-algal testing was also carried out as is described in more detail in Examples 13 to 16.

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These test organism~s will be referred to hereafter as EC, PA, SA, BS, AA, AN. AP, CS, CH, PP, GR, CG and CA respectively.

Microbiostatic evaluation - A) A~ar tRst The material to be tested was dissolved in a suitable solvent and the solution obtained diluted with a further quantity of the same solvent to give a desired product concentration.

To a suitable agar medium was added a quantity of the product solution to give a desired concentration of the product. The agar medium containing the product was poured into petri dish plates and allowed to set.

The test organisms were surface inoculated onto the test plates by means of a multi-point inoculator. Each test plate was inoculated with both bacteria and fungi. The plates were incubated for four days at 25~C.

At the end of the incubation period, the plates were assessed visually for growth of the micro-organisms. The concentration of the product which inhibited the growth of a particular-micro-org~nism was recorded.

B) Microtitre AssaY

A sample of the product to be tested was either dissolved in N,N-dim~thylformamide to give a concentration of 5g. dm~3 or, with a product which is insoluble in N,N-dimethylformamide, the product is dispersed in water by milling in water for at least 72 hours to give a dispersion concentration of 5g. dm 3.

For testing against bacteria. n~lcm3 of a fresh stationary phase culture of the bacterium (having at least 108 cells per cm3~
were added to lOOcm3 of nutrient broth and mixed. O.lcm3 aliquots of the mixture were dispensed into microtitre ~ells with the exception of the first row of the plate into which an 0.2cm3 aliquot was placed. 0.02cm3 of the solution or dispersion of the product to be tested was added to the first well (which contained an 0.2cm3 aliquot) and mixed. O.lcm3 of this mixture was removed, transferred to the well in the adjacent row and mixed, this serial dilution procedure being effected across the plate until the last well when O.lcm3 was discarded. Incubation was effected for 24 hours at 37C.

For testing against fungi a similar procedure was used with the following modifications:-A fresh spore suspension of the fungus was made up in sterile saline (this contained 109 cells per cm3) and was used instead of a stationary phase culture. Malt broth was substituted for nutrient broth. Incubation was effected for 72 hours at ~5C.

Any precipitation of the compound being tested was noted before incubation since precipitation could interfere with assessment of ~he results. At the end of the incubation period, the plates were assessed visually for inhibition of growth of the micro-organisms.
The concentration of the product which inhibited the growth of a particular micro-organism was recorded.

_~ample 1 A PrePAration of Z-hydrosv-2.3-dihydro-l~-isoindol l-one The procedure was in accordance with the method of O Neunhoeffer and G Gottshelch Ann. Chem 1970, (736) lO0.

A solution of 13.4g (0.1 mol) of phthalic dicarboxaldehyde in methanol (30cm ) was added to a solution of 6.9g (0.1 mol) of hydroxylamine hydrochloride and lOg (0.094 mol) of sodium carbonate in water (200cm3).

The mixture was stirred at ambient temperature until reaction was complete as determined by thin layer chromatography (tlc) (about 6 hours). The solution was washed with chloroform - (lOcm3), the pH was adjusted to seven by the addition of normal hydrochloric acid and the neutral solution was extracted with chloroform (4x40cm3). The combined chloroform extracts were chilled to 4C overnight to yield a grey solid which was crystallised from a 1:1 by volume mixture of chloroform and diethyl ether. 2-hydroxy-2,3-dihydro-lH-isoindol-l-one having a melting point of 191 - 2C, was obtained in a yield of 2.38g (16Z). By analysis the product was found to contain C, 64.0~ wt, H 4.7~ wt and N 9.3~ wt. C8H7N02 requires C 64.4~ wt, H 4.7~ wt, H 4.72 wt and N 9.4Z wt. The mass spectral data is consistent with the product being 2-hydroxy-2,3--dihydro-lH-isoindol-l-one.

B. Prepar_tio~ of Z-Acsto~y-2.3-dihYdro-l~-isoindol-l-one 2.24g (15.0 mmol) of 2-hydroxy-2,3-dihydro-lH-isoindol-l-one, obtained as described in Part A, 1.26g tl5.0 mmol) of sodium hydrogen carbonate and 2.0g of a 42 molecular sieve were added to dry dichloromethane (50cm3). The mixture was stirred, cooled on ice and a solution of 3.53g (45.0 mmol) of acetyl chloride in dichloromethane (20cm3) was added over 10 minutes. The solution was allowed to warm to ambient temperature and, after two hours at ambient temperature, a further 3.53g (45.0mmol) of acetyl chloride, together with 2.07g (15.0 mmol) of potassium carbonate were added. The resulting mixture was stirred overnight at room temperature, filtered and evaporated to a crude grey solid. 2-acetoxy-2,3-dihydro-lH-isoindol-l-one having a melting point of 69-71C was obtained in a yield of 2.62g (99Z). The infra red absorption spectrum showed peaks at 1800, 1705, 1152, 1003 and 729 cm~l. The mass spectral data is consistent with the product being 2-acetoxy-2,3-dihydro-lH-isoindol-l-one.

~2~ 3~

C. Preparatlon of 2-hy~ro~y-2,3-dihydro-1~-isoindol-1-thione 2.33g (13.2 mmol) of crude 2-acetoxy-2,3-dihydro-lH-isoindol-l-one, prepared as described in Part B, were dissolved in dry dichloromethane (100cm3), 5.66g (14.0 mmol) of Lawesson's reagent were added and the mixture reluxed for 48 hours, at which time tlc indicated reaction was complete. The organic mixture was evaporated to a dark green sludge which was dissolved in a mixture of tetrahydrofuran (14cm3~ and water (lOcm3). The mixture was stirred at 50C and an aqueous sodium hydroxide solution was added dropwise to maintain the pH at 8-9. Once the pH had stabilised, the aqueous mixture was stirred for a further hour before cooling to 0C and adding a further quantity of the aqueous sodium hydroxide solution to raise the pH to 10. The basic solution was washed with diethyl ether (4 x 50cm3), acidified with 6M aqueous hydrochloric acid and extracted with diethyl ether (4 x 50cm3). The combined diethyl ether extracts were washed with water, dried over anhydrous magnesium sulph&te and evaporated to an orange oil. This was flash chromatographed on silica with a petroleum ether (60 - 80) ethyl acetate mixture of varying composition 8S eluant. The ferrlc chloride positive fractions were combined and evaporated. The residue was purified by dlssolving in toluene, adding charcoal, stirring the mixture, filtering to remove the charcoal and then crystallising. 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione, having a melting point of 110-1C was obtained in a yield of 0.33g (15~). By analysis the product was found to contain C 58.5~ wt and H
4.3~ wt. C8H7NOS requires C 58.2% wt and H 4.2~ wt. The infra red absorption spectrum showed peaks at 1497, 1335, 1290 and 1203 cm~l.
The proton n.m.r. spectnlm and mass spectral data are consistent with the product being 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione.

-D. PreParation of 2-hydro~Y-2.3-dihYdro-l~-isoindol-l-thione zinc complex ~2.1) 200mg(1.2 mmol) of 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione, obtained as described in Part C, were dissolved in methanol (20cm ) and a solution of 140mg (0.6 mmol) of zinc acetate in methanol (20cm3) was added. A grey precipitate appeared.
Distilled water (40cm3) was addedt the crude product was collected and then crystallised from chlorobenzene. 2-hydroxy-2,3-dihydro-lH-isoindol-l-thione zinc complex (2:1) having a melting point of 259C was obtained in a yield of 200mg (84~). By analysis the product was found to contain C 48.0~ wt, H 3.0Z wt and N 6.8Z wt.
C16H12N202S2 Zn + 1~ H20 requires C 48.3~ wt, H 3.15Z wt and N 7.0~ wt. The infra red absorption spectrum showed peaks at 1501, 1297, 1212, 762 and 689 cm~l. The proton n.m.r. spectrum and mass spectral data are consistent with the product being a 2:1 complex.

This material will be referred to as "Compound ln.

Example 2 A. Preparatlo~ of l-~dro~-2-p~rrolidinone To a solution of 5.19g (30 mmol) of N-hydroxybenzene-sulphonamide in ethanol (30 cm3) at -10C (salt ice bath) were added 30cm3 of a lN aqueous solution of sodium hydroxide (30 mmol) with stirring. After 10 minutes, 2.1g (30 mmol) of cyclobutanone were added and the mixture was stirred at -10C for a further one hour.
The mixture was allowed to wan~ up to ambient temperature and left for two days. The mixture was acidified with 30cm3 of l.lN
hydrochloric acid, evaporated and the residue purified by silica-gel g -1~- S 35357 chromatography using ethyl acetate as the initial eluant, progressively containing a higher proportion of methanol, up to 20Z
methanol by volume. 2.22g (73% yield) of ~he product were obtained as a syrup. A small sample of this product was crystallised from toluene and was found to have a melti.ng point of 62C. By analysis the product was found to contain C 47.0~ wt, H 7.8% wt and N 13.7~ wt. C4~7NO2 requires C 47.5Z wt, H 6.9% wt, and N 13.86~ wt.
Protor. n.m.r. and C 3 n.m.r. spectra, and the mass spectral data, were consistent with the product being l-hydroxy-2-pyrrolidinone.

B. Preparation of l-Aceto~y-2-D~rrolidinone To a stirred mixture of 2.0g (19.8 mmol) of l-hydroxy-2-pyrrolidinone, prepared as described in Part A, 4.0g (47.5 mmol) of sodium hydrogen carbonate, Sg of a 4A molecular sieve and 60cm3 dry dichloromethane at 0C were added 9.33g (0.119 mol) of acetyl chloride. The mixture was allowed to warm up to ambient temperature and was stirred st ambient temperature for 24 hours. The mixture was filtered and the filtrate evaporated. The residue of the evaporation was purified by silica-gel chromatography using a 1:1 petroleum ether/ethyl acetate mixture as the initial eluant, progressively containing more ethyl acetate to 100% ethyl acetate.
2.77g (98~ yield) of the product were obtained as a syrup.

The infra red absorption spectrum showed peaks at 2924, 1797, 1714, 1460, 1393, 1359, 1269, 1178 and 1043 cm~l. The proton n.m.r. spectrum was consistent with the product being 1-acetoxy-2-pyrrolidinone.

C ~ ~ 9 ~

C. Preparation nf ~-Ac~tn~y- yrrolidinthione A mixture of 2.64g (18.46 mmol) of l-acetoxy-2-pyrrolidinone, prepared as descrihed in Part B, 7.47g (18.46mmol) of Lawesson~s reagent and 70cm3 dry dichloromethane was heated under reflux with stirring for four hours. The mixture was cooled to ambient temperature, and filtered. The filtrate was evaporated to dryness and the residue purified twice by silica-gel chromatography using a mixture of hexane and ethyl acetate as eluant, initially a 2:1 volume mixture containing a progressively higher proportion of ethyl acetate to a 1:1 volume mixture. 2.8g (95~ yield) of the product were obtained as a syrup. The inra red absorption spectrum showed peaks at 2~91, 1793, 1501, 1449, 1420,-1367, 1303, 1276 and 1156cm~l. Proton n.m.r. and C13 n.m.r. spectra, and the mass spectral data, were consistent with the product being 1-acetoxy-2-pyrrolidinthione.

This material will be referred to as "Compound 2 n .

E~a~E~le 3 A. Pre~aratic!n of Zi~c trimethylsilanolate lOOcm3 of a 0.5M solution of zinc bromide in dry tetra-hydrofuran were cooled to 0C and stirred under argon. To this solution were added, dropwise, lOOcm3 of a lM solution of sodium trimethylsilanolate in dry tetrahydrofuran, The mixture was allowed to warm up to ambient temperature and was stirred overnight. The mixture was filtered. The filtrate was used as a 0.25M solution of zinc trimethylsilanolate in tetrahydrofuran.

B. Pre~aration of l-~Ydro~y-2-py~olidinthione zinc co le~ (2:1) To O.Z67g (1.68 mmol) of 1-acetoxy-2-pyrrolidlnthione, prepared as described in Part C of Example 2, under argon at 0C
were added, with stirring, 3.36cm3 of the solution of zinc trimethylsilanolate in tetrahydrofuran obtained in Part A. After 18 hours, a solid product (96mg) was collected by filtration and washed with 5cm3 of tetrahydrofuran A further crop of a solid product (50mg) was obtained by partial evaporation of the filtrate.
The combined solid product (0.146g, 59Z yield) had a melting point of 202C. By analysis the product was found to contain:- C 32.1Z wt;
H 4.1~ wt and N 9.22 wt. C8H12N2O2S2Zn requires C 32.27Z wt, H 4.062 wt and N 9.41Z wt. The infra-red spectrum showed peaks at 2948, 1558, 1312, 1151 and 1142cm~l. Proton n.m.r. and mass spectral data were consisten~ with the product being a 2:1 complex.

This material will be referred to as "Compound 3 n E~ample_4 A. Preenrntion of l-Aceto~-5.5-dimethy~-2-P~rrolidinone To a stirred mixture of 2.8g (21.7 mmol) of 5,5-dimethyl-l-hydroxy-2-pyrrolidinone, prepared as described in J. Chem.
Soc (1959) pages 2094-2102, 4.3~3g (52.1 mmol) of sodium hydrogen carbonate, 7.0g of 4A molecular sieve and 60cm3 dry dichloromethane, cooled to 0C were added 10.22g (0.13mol) of acetyl chloride.

f~ 6 The mixture was allowed to warm up to ambient temperature and stirred at ambient temperature for four hours. The mixture was filtered and the filtrate evaporated. The residue of the evaporation was purified by silica-gel chromatography using a 1:1 volume mixture of petroleum ether and ethyl ~cetate as the initial eluant, progressively containing more ethyl acetate to 100% ethyl acetate. 3.7g (100~ yield) of the product was obtained as a syrup.
The infra red absorption spectrum showed peaks at 2969, 1794, 1718, 1396 and 1190 cm~l. The proton n.m.r. spectrum was consistent with the product being 1-acetoxy-5,5-dimethyl-2-pyrrolidinone.

B. Preparation of l-Acetorr-5,5-dimethYl-2-pyrrolidinthione ~ mixture of 3.30g t20.5 m~ol) of l-acetoxy-5,5-dimethyl-2-pyrrolidinone, prepared as described in Part A, 8.29g (Z0.5 mmol) of Lawesson's reagent and 70 cm3 of dry dichloromethane was heated under reflux with stirring for 3.75 hours.
The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated to dryness and the residue purified by silica -gel chromatography using a 4:1 volume mixture, changing progressively to a 2:1 volume mixture, of petroleum ether and ethyl acetate as eluant. The product was crystallised from a 1:1 petroleum ether/ethyl acetate mixture. 2.65g (74% yield) of a solid having a melting point of 90 - 91C were obtained. By analysis the solid product waR found to contain C 51.5~ wt; H 7.4%wt; N 7.2% wt and S
16.9~ wt. C8H13N02S requires C 51.31% wt; H 7.00% wt; N 7.4~ wt and S 17.122 wt. The infra red absorption spectrum showed peaks at 2g74;
1800; 1443: 1410; 1366; 1201; 1163 and 1078cm 1. Proton n.m.r. and mass spectral data were consi~tent with the product being l-acetoxy-5,5-dimethyl-2-pyrrolidinthione.

This material will be referred to as "Compound 4 n, s~ 2 ~

E~am~

A. Preparation of 5,5-Dimethyl-l-hydro~y-Z-PYrrolidinthione zinc com~le~ (2:1) To l.oB (5.35 mmol) of 1-acetoxy-5,5-dimethyl-2-pyrrolidin-thione, prepared as described in Part B Oc Example 4, under ar~on were added, with stirring, 32.lcm3 of the solution of zinc trimethyl-silanolate in tetrahydrofuran obtained in Part A of Example 3. The solution of the æinc compound was added in three equal portions over two days (at O,l and 2 days). After a further day, lcm3 of water was added, the mixture was evaporated and the residue purified by silica-gel chromatography using a 9:1 volume mixture, changing progressively to a 2:1 volume mixture, of petroleum ether and ethyl acetate as the eluant. The product was recrystallised from 1:1 volume hexane-ethyl acetate mixture. 0.55g (58.5% yield) of a solid product having a melting point of 174-176JC was obtained. By analysis the solid product was found to contain C 41.2% wt;
H 6-0Z wt; N 7-3% wt and S 17.0~ wt. Cl2~20o2s2N2zn requires C 40.74Z wt; H 5.7% wt; N 7.9% wt and S 18.12% wt. The infra red absorption spectrum showed peaks at 2972, 1546 and 1208 cm~l.

The proton n.m.r. spectrum, and mass spectral data are consistent with the product being a 2:1 complex.

This material will be referred to as "Compound 5 n .

E~ample 6 to 9 The products of Examples 1,3,4 and 5 were evaluated against a range of micro-organisms using the procedure of the Microtitre Assay as herein before described. Control of the test organisms was obtained at the levels set out in the Table One.

¦ Test ¦ COMPOUND (b) ¦ Organism I 1 j 3 ¦ 4 ¦ 5 ¦ A ¦ B
I (a) I (ppm) I (ppm) I (Ppm) I (ppm) I ~pPm) I (Ppm ¦ EC ¦ Z ¦ 4 ¦<4 l l 14 ¦ 8 I PA ¦16 ¦ 16 ¦125 1 8 ¦16 ¦32 ¦ BS ¦ 1 ¦ 1 ¦ND ¦<0.25¦ 4 ¦ 2 ¦ M ¦ 2 ¦ 4 ¦ND ¦ 1 12 ¦31 ¦ AN ¦ 2 ¦ 16 ¦31 1 8 12 1 8 ¦ AP ¦ 4 ¦ 8 ¦ND ¦~0.25¦ 1 1 2 CH ¦ 8 ¦ 4 IND ¦ 8 11 ¦ 4 CG ¦ 4 ¦ 4 ¦ND I 8 11 ¦ 4 1. 1 . 1_ 1 1 1 Note~ to T~ble Qne (a) Organisms are as previously defined herein, the specific strains used being (b) 1,3,4-snd 5 are Compounds 1,3,4, and 5 as previously defined herein.
A i8 8 complex as obt~ined in Example 2 of European Patent Application Publication No 249328.
B is a complex as obtained in Example 17 of European Patent Application Publication No 249328.
ND means ~Not Determined~, the product was not tested against this test organism.

The lowest level of product tested was 0.25ppm with the exception of compound 4 which was tested to a lowest level of 4 pp~.

EYamples 10 to 12 The products of Examples 2,3 and 5 were evaluated against a range of micro-organisms using the procedure of the Agar test as hereinbefore described. Control of the test organisms was obtained At the levels set out in Table Two.

TABLE TWO

¦ Test I COMPOUND (b)(d) Orgsnism 1~
I (a) (c) I 2 1 3 1 5 I l(ppm~ I (ppm) I (~pm) ¦ EC ¦ ~25 ¦ ~25 1 ~25 ¦ PA ¦ 500 1 ~25 ¦ 100 SA ¦ ~25 ¦ ~25 ¦ ~25 ¦ BS ¦ ND ¦ ~25 ¦ ~25 ¦ AN ¦ 500 ¦ 100 ¦ 100 ¦ AP ¦ ~25 ¦ S 5 ¦ ~ 5 CS ¦ 500 ¦ ND I ND
¦ M ¦ ~25 I ND I ND
CG ¦ 500 ¦ ND I ND
I GR ¦ ND ¦ ~ 5 ¦ ~ 5 ¦ PP ¦ ND ¦ ~ 5 ¦ ~ 5 I CA ¦ ND ¦ >100 ¦ ~100 Notes to Table Two ~a) and (b) are both as defined in Notes to Table One, with the exceptions noted in (c) in respect of the test organisms.
(d) ~ indicates that the product provided control of the test organism at the lowest level of product tested.
> indicates that the product failed to control the test organism at the highest level of the product tested.

(c) Organisms are as previously defined herein and in Note (a) to Table One, the strains being:-Exam~les 13 to 16 The products of Examples 1, 3, 4 and 5 were evaluated against an algal medium using the following procedure:-lOcm3 aliquots of an algal broth medium were placed in test tubes which were then capped. A chemical under test was added to the medium to give concentrations of from 0.16ppm to lOppm of the chemical.

Each test tube was inoculated with O.lcm3 of a mixed algal suspension which was a 7 dey culture of a mixture of the following algae:-Stichococcus bacillaris Gloecapsa alpicola Nostoc commune Trentepohlia aurea The test tubes were incubated at ambient temperature (15-20C) with artificisl illumination of between 700 and 1200 LUX
provided to give 16 hours of illumination and 8 hours of darkness in every 24 hour period. After two weeks, the contents of the test tube were re-inoculated with O.lcm3 of the mixed algal suspension as described previously.

2 ~ 2 1~

The incubation with alternate periods of light and dsrk was continued for a period of a further four weeks. The contents of the test tubes were then assessed visually for algal growth. The concentration of each chemical which completely inhibited algal growth was noted and the results are set out in Table Three.

TABLE THREE

... . _ ÇOmpound ¦ Ex or ¦ Type I ppm ¦ Comp Ex ¦ (b) 101 (e~

13 1 1 1 2.5 14 1 3 1 2.5 1 16 1 5 1 0.64 ¦ C* I NIL ¦ NIL

Notes to Table Three (b) is as defined in Notes to Table One (e)* Extensive growth of algae was observed with a pronounced green colouration after seven days.

Claims

1. A biocide composition which contains an effective amount of at least one compound of the formula I:- (I) or a salt or complex thereof, together with a carrier material, wherein X is a group -CR1R2- or a group -CR1=;
Y is a group -CR3R4- or a group -CR3=;
Z is a group -CR5R6- or a group -CR5=;
R is a hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -COOR7;
R1 to R6 are each, independently, a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group, or R1 and R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or R1 and R3 together with the carbon atoms to which they are attached, form a ring, or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group.

2. The composition of claim 1 wherein X is -CH2- or -C(CH3)2-.

3. The composition of claim 1 which contains a complex with zinc.

4. The composition of claim 1 which contains at least one compound or one complex which is 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione/zinc 2:1 complex:
1-acetoxy-2-pyrrolidinthione;
a 1-hydroxy-2-pyrrolidinthione/zinc 2:1 complex;
1-acetoxy-5,5-dimethyl-2-pyrrolidinthione; or a 5,5-dimethyl-1-hydroxy-2-pyrrolidinthione/zinc 2:1 complex.

5. The composition of claim 1 wherein the compound of formula I, or a salt or complex thereof, is in solution, suspension or emulsion in a liquid.

6. The composition of claim 1 wherein the carrier is a water soluble solid material.

7. The composition as claimed of claim 1 which contains from 0.0001% up to 50% by weight, of the composition, of the compound of formula I or a salt or complex thereof.

8. A compound of the formula wherein X1 is a group -CR1R2- or a group -CR1=;
Y1 is a group -CR3R4- or a group -CR3=;
Z1 is a group -CR5R6- or a group -CR5=;
R is a hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -COOR7;

R1 to R6 are each, independently, a hydrogen atom. a hydrocarbyl group or a substituted hydrocarbyl group. or R1 or R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or R1 and R3 together with the carbon atoms to which they are attached, form a ring, or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group with the exceptions that when X1 is -C(CH3)2-, R is -H or -CH3 and Y1 is -CH2-, Z1 is neither -CH2- nor -C(CH3)2-; and when X1 is -C(CH3)2-, R is -H or -CH3 and Z1 is -CH2-, Y1 is neither -CH(CH3)- nor -CH(C6H5)-.

9. The compound of claim 8 wherein X1 is -CH2-.

10. A salt or complex of a compound of the formula I:- (I) wherein X is a group -CR1R2- or a group -CR1=;
Y is a group -CR3R4- or a group -CR3=;
Z is a group -CR5R6- or a group -CR5=;
R is a hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -COOR7;
R1 to R6 are each, independently, a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group, or R1 and R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or R1 and R3 together with the carbon atoms to which they are attached, form a ring, or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group.

11. The salt or complex of claim 10 wherein X is -CH2-.

12. The salt or complex of claim 10 which is a complex with zinc.

13. 1-acetoxy-2-pyrrolidinthione; or 1-acetoxy-5,5-dimethyl-2-pyrrolidinthione.

14. A 2:1 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione/zinc complex;
a 2:1 1-hydroxy-2-pyrrolidinthione/zinc complex; or a 2:1 5,5-dimethyl-1-hydroxy-2-pyrrolidinthione/zinc complex.

15. A method for inhibition the growth of micro-organisms on, or in, a medium which comprises treating the medium with a compound of the formula I:- (I) or a salt or complex thereof, or with a biocide composition which contains a compound of the formula I or a salt or complex thereof, wherein X is a group -CR1R2- or a group -CR1=;
Y is a group -CR3R4- or a group -CR3=;
Z is a group -CR5R6- or a group -CR5=;
R is a hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -COOR7;
R1 to R6 are each, independently, a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group, or R1 and R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or R1 and R3 together with the carbon atoms to which they are attached, form a ring, or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group.

16. The method of claim 15 wherein the biocide composition or the compound, salt or complex is incorporated or impregnated into the medium in an amount to provide from 0.001 up to 2% by weight of the compound, salt or complex relative to the weight of the medium.

17. The method of claim 15 wherein at least one further antimicrobial compound is used.

18. A process for the preparation of a compound of the formula I:- (I) or a salt or complex thereof, which process includes the steps of reacting 1-hydroxy-2-pyrrolidinone, a derivative thereof, 1-hydroxy-2-pyrrolinone or a derivative thereof with an acid halide and treating the esterfied product with Lawesson's reagent, wherein X is a group -CR1R2- or a group -CR1=;
Y is a group -CR3R4- or a group -CR3=;
Z is a group -CR5R6- or a group -CR5=;
R is a hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, an acyl group, a substituted acyl group or a group -COOR7;
R1 to R6 are each, independently, a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group, or R1 and R2, together with the carbon atom to which they are attached, form a ring, and/or R3 and R4, together with the carbon atom to which they are attached, form a ring, and/or R5 and R6, together with the carbon atom to which they are attached, form a ring; or R1 and R3 together with the carbon atoms to which they are attached, form a ring, or R3 and R5, together with the carbon atoms to which they are attached, form a ring; and R7 is a hydrocarbyl group.

l9. The process of claim 18 which process includes an initial step of preparing 1-hydroxy-2-pyrrolidinone by reacting cyclobutanone with N-hydroxybenzenesulphonamide in the presence of a base.

20. The process of claim 18 which includes an initial step of reacting a 1,2-dialdehyde with hydroxylamine.

21. The process of claims 18 wherein the product obtained by treatment with Lawesson's reagent is reacted with a metal trialkylsilanolate.