GB2281210A - Biocidal compositions containing organoboron compounds - Google Patents

Abstract

A liquid biocidal or preservative composition which is enzyme free comprises (i) as active ingredient at least one borinic, boronic or diboronic acid, (ii) at least one surfactant, and (iii) an aqueous or organic solvent or carrier and is highly effective in protecting porous substrates, particularly cellulosic substrates such as timber, from attack by fungi, bacteria or insects.

Description

Biocidal Compositions containing Organoboron Compounds This invention relates to a liquid biocidal or preservative composition containing an organoboron compound, particularly for the control of pests, including insects, fungi and bacteria, that can cause considerable damage to substrates that support organic growth, especially timber.

The invention provides also a method for protecting a porous substrate with a cellulosic base, such as timber, particle board and chipboard, from deterioration caused by insects, fungi and bacteria.

There are many methods known to the art for protecting timber from the action of wood-destroying organisms and for the eradication of these organisms. By way of illustration, world-wide, termites (order Isontera) are the most destructive to wood. Their attack on timber can lead to cosmetic damage and ultimately structural failure of wooden constructions.

Inorganic borates have been used as active ingredients in timber preservation for many years and show activity against fungi and insects such as white and brown rots, beetles and termites. For example, US-A-4,719,110 describes solutions containing inorganic borate preservatives, such as borax and sodium polyborates, that are applied to unseasoned timber by dipping for a period sufficient to allow diffusion of the borate into the wood.

A particular beneficial characteristic of borate compositions is their efficacy as preservatives allied to low mammalian toxicity. This makes them safe to handle both before and after application. For this reason they are preferred in many applications to compositions containing more toxic combinations such as chromium, arsenic and chlorinated phenols.

Stable organoboron compounds, namely boronic, diboronic and borinic acids are known and can be synthesised by methods known to the art.

It is known that boronic acids are inhibitors of the activity of proteolytic enzymes as used, for example, in liquid detergents. PCT patent application PCT/US92/03372, published as WO 92/19707, describes the use of aryl boronic acids, substituted at the 3- position relative to boron, as an inhibitor of proteolytic enzymes in liquid detergent compositions to protect enzymes in the compositions. The inhibition is reversible upon dilution with water and the enzyme's activity is regained, as happens in a washing cycle.

We have now found that certain boronic, diboronic and borinic acids have biocidal activity showing greater efficacy than that found in inorganic borates previously described.

According to the invention there is provided a liquid biocidal or preservative composition which is enzyme free and comprises, (i) as active ingredient at least one organoboron compound of formula (I), (II) or (III),

in which formulae R1 and R3, which may be the same or different, each represents an optionally substituted alkyl, cycloalkyl, aralkyl or aryl group of up to 20 carbon atoms, which can have a monocyclic or fused ring structure of up to 18 ring carbon atoms, an optionally substituted heterocyclic group containing at least one nitrogen, oxygen or sulphur heteroatom, which can have a monocyclic or fused ring structure of up to 17 ring carbon atoms, or an optionally substituted quinoid group, which can have a monocyclic or fused ring structure of up to 18 ring carbon atoms, R2 and RX, which may be the same or different, each represents a divalent group of the formula

wherein each X, which may be the same or different, is hydrogen, optionally substituted alkyl of up to 6 carbon atoms, optionally substituted aryl, hydroxy or a derivative thereof, halogen, optionally substituted amino, nitro, thiol or a derivative thereof, aldehyde, carboxylic acid or salt or ester thereof, sulphonate or phosphorate, and o, p and q are each 0, 1 or 2, and m and n, which may be the same or different, are each zero or 1, or a salt of such an organoboron compound; (ii) at least one surfactant; and (iii) an aqueous or organic solvent or carrier.

Preferably the organoboron compound is of formula (I) or (II) in which m and n are each zero and R1 and R3, which may be the same or different, are each an optionally substituted group selected from alkyl of up to 10 carbon atoms, cycloalkyl of up to 8 carbon atoms, aralkyl of up to 16 carbon atoms wherein the aryl moiety has up to 12 carbon atoms and the alkyl moiety has up to 4 carbon atoms or a nitrogen- or sulphur-containing heterocyclic group. Organoboron compounds in which R1 and R3 are each an optionally substituted group selected from n-alkyl of up to 10 carbon atoms, cyclohexyl, phenyl, naphthyl, benzyl, phenylethyl, phenylpropyl, diphenylethyl or thiophenyl are especially preferred.

Suitable optional substituents are at least one atom or group selected from halogen, C1-C4 alkyl, C1-CX alkoxy and trifluoromethyl. Examples of organoboron compounds which can be used as the active ingredient in the compositions of the invention include the following; alkyl boronic acids such as n-butyl boronic acid, n-heptyl boronic acid, n-octyl boronic acid and n-nonyl boronic acid, cycloalkyl boronic acids such as cyclohexyl boronic acid, aralkyl boronic acids such as pbromophenylethyl boronic acid, phenylethyl boronic acid, phenylpropyl boronic acid, biphenylethyl boronic acid, 3bromophenylethyl boronic acid and 2-naphthylethyl boronic acid, aryl boronic acids such as phenyl boronic acid, 4chlorophenyl boronic acid, 4-bromophenyl boronic acid, 4fluorophenyl boronic acid, 2-chlorophenyl boronic acid, 3bromophenyl boronic acid, 4-methylphenyl boronic acid, 2methylphenyl boronic acid, 3-methylphenyl boronic acid, mesityl boronic acid, 4-methoxyphenol boronic acid, 3,5bis(trifluoromethyl) phenyl boronic acid, 2,4-dichlorophenyl boronic acid, 3-chloro-4-fluorophenyl boronic acid, 3,5dichlorophenyl boronic acid and l-naphthalene boronic acid, heterocyclic boronic acids such as 3-thiophene boronic acid, and borinic acids such as diphenyl borinic acid.

Suitable salts of the organoboron compounds of formula (I), (II) and (III) are sodium, potassium, copper, zinc, barium, magnesium, calcium, iron, manganese, cobalt, nickel or silver salts.

Borates are well known to undergo chelate complex formation with compounds containing polyols and it is believed that such complexation with compounds of biological importance is the mechanism by which inorganic borates act as biocides and wood preservatives. The compounds used as active ingredient in the compositions of the invention are thought to undergo a similar interaction with polyols and additionally have further advantages which will become apparent, that lead to greater efficacy over inorganic borates previously used.

Generally the organoboron compounds used according to the invention have a low solubility in water and, when using water as a carrier, they may be dissolved in an organic solvent and further diluted with water in the presence of at least one surfactant, as an emulsion, microemulsion, liquid crystal phase or liquid crystal phase dispersion.

Depending on the application, in use the biocidal compositions of the invention typically contain up to 10% by weight of the organoboron compound as the biocidally active ingredient. Preferably there is between 0.01 and 1.0% of active ingredient. These compositions are preferably prepared in situ by diluting a concentrate with water. The concentrate may contain up to 60% by weight of the organoboron compound.

In preferred compositions, the content of the organoboron compound in concentrates is in the order of 10% by weight.

In one aspect of the invention, the concentrate is in the form of a microemulsion. Methods for preparing microemulsions using one or more surfactant are known to those skilled in the art. By way of example, 1 part by weight of octylboronic acid can be dissolved in 10 parts by weight of an organic solvent such as petroleum distillate or kerosene, 8 parts by weight of an ionic surfactant such as an alkyl benzene sulphonate, and 12 parts of a co-surfactant such as a C4-C6alcohol are added.

The mixture is agitated to form a microemulsion useful for treating wood on dilution with 170 parts of water. Part of the water can be used in making the concentrate to ease blending on dilution with further water.

Preferably combinations of surfactants or a surfactant plus a co-surfactant are used. These can be mixtures of high and low hydrophile-lipophile balance (HLB) non ionic surfactants such as ethoxylated alcohols and nonylphenols or anionic/nonionic mixtures such as low HLB ethoxylated nonionic surfactants with ionic surfactants, for example, alkylaryl sulphonates, alkyl sulphates, fatty acid salts in combination with co-surfactants such as short to medium chain alcohols.

The solvent in which the organoboron compounds are usually dissolved may be one or a mixture of a range of solvents, including white spirit, kerosene, aromatic esters or lower alcohols.

In a modification of the invention, products containing amounts of, or comprising entirely, surfactant liquid crystal phases are produced which have customised rheological properties such as viscoelasticity, which is useful to suspend particulates in the formulation. In this case, surfactant concentrations are in the order of 10-20% by weight of the product. Preferred surfactants include a phosphate ester plus an ethoxylated ionic or pairs of high and low HLB nonionics.

In other embodiments, stable emulsions can be formulated using between 0.5 and 5.0% by weight surfactant based on the weight of emulsified solvent in the concentrate. A wide range of surfactants or surfactant combinations may be used which may be anionic, cationic, non-ionic or zwitterionic. A typical example is a nonylphenol ethoxylate with between 7 and 14 moles ethylene oxide. Up to 80% by weight of solvent containing the dissolved organoboron compound can be incorporated into the emulsion.

Alternatively, biocidal compositions can be prepared as suspensions incorporating a suitable thickening agent such as a carboxymethyl cellulose or a xanthan gum.

The liquid compositions of the invention can be applied to a porous substrate by simple brushing, dipping or spraying techniques. If desired vacuum or pressure application can be used to promote penetration of the substrate by the liquid composition.

The organoboron compounds used in the compositions of the invention can be prepared by known methods. For example, the hydroboration of unsaturated materials, i.e. alkenes and alkynes, using either catecholborane (1,3,2-benzodioxaborole) or dichloroborane-dimethyl sulphide complex as the hydroborating agent is described in J. Amer. Chem. Soc., 97 (18), 1975, 5249-5255. Catecholborane reacts rapidly with the alkenes and alkynes at 1000 and 700C respectively, to give corresponding alkyl- and alkenylcatecholboranes in high yield.

The alkyl- and alkenylcatecholboranes undergo rapid hydrolysis with water to give the corresponding alkane- and alkeneboronic acids.

A Grignard synthesis for manufacturing boronic acids is described in J. Amer. Chem. Soc., 54, 1932, 4415-4425 and J.

of Shivasi University, 1932, 6(12), 11-13, wherein there is described preparation of phenylboronic acid and other substituted boronic acids by the action of appropriately substituted organo-magnesium bromides on trip'butyl borate or trimethyl borate at low temperatures followed by hydrolysis of the boronic ester thus formed.

The reaction of an organolithium reagent with butylborate to form boronic acids is described in Thiophene Chemistry, Part VII, 387-393 and C.R. Acad. Sc. Paris t.270, 1608-1610.

The borinic acids for use according to the invention are preferably prepared by Grignard synthesis with a ratio of Grignard reagent to borate of 2:1. Diboronic acids are prepared by selecting the appropriate Grignard Reagent and proceeding according to the methods for Grignard synthesis of boronic acids.

All nuclear substitutions and protection of functional groups can be achieved using methods well known to those skilled in the art.

The preparation of typical boronic and borinic acids for us according to the invention will now be described, and f lowed by examples of biocidal applications.

P paration of 3-thiopheneboronic acid 3- Bromothiophene (5g,0.03M) in sodium dried ether (100ml) was cooled to -600. Butyllithium (30ml of 1M) was added rapidly. The mixture was then stirred for three minutes and butyl borate (lOg,0.043N) in sodium dried ether (25ml) was added. The mixture was then stirred for four hours and allowed to warm to room temperature. The reaction mixture was then treated with hydrochloric acid (1M) and the ether layer separated. The aqueous layer was extracted with ether (2x25ml). The combined ether layers were extracted with sodium hydroxide (1N). The alkaline solution was then acidified with hydrochloric acid (10%) thus precipitating the desired boronic acid. The boronic acid was isolated and then recrystallised from water/ethanol. It was allowed to dry in air.

The product had a melting point of 163-1640C.

Synthesis of l-naDhthalene boronic acid A Grignard reagent was prepared by the slow dropwise addition of l-bromonaphthalene (10.4g, 0.05M) in sodium dried ether (50ml) to magnesium turnings (1.2g, 0.05M) also in sodium dried ether (50ml). The reaction was encouraged by the addition of a small crystal of iodine.

Tri-n-butyl borate (11.5g, 0.05N) in sodium dried ether (50ml) was cooled to -700C. The Grignard reagent was added dropwise over a period of two hours to the borate solution; the temperature of the reaction was maintained at -700C throughout the addition.

The reaction mixture was then allowed to warm to room temperature overnight. The mixture (an orange solution) was hydrolysed by the dropwise addition of dilute sulphuric acid (10%). The ether layer was separated and the aqueous layer extracted with ether (2x30ml). The fractions were combined and the ether removed. The residue was made distinctly alkaline by the addition of sodium hydroxide (10%) and the butanol thus formed was removed by steam distillation - the volume was maintained at about 100ml throughout the distillation by the addition of distilled water. Crystals formed at this stage were removed by filtration. The remaining solution was made slightly acidic (H2SO4, 10%) and the crystals so formed were removed. The combined l-naphthalene boronic acid crystals were recrystallised from distilled water.

The product had a melting point of 210-2110C.

Preparation of diphenylborinic acid Diphenylborinic acid was prepared using essentially the same method as for l-naphthalene boronic acid. The Grignard reagent was prepared from bromobenzene and magnesium turnings.

However, two moles of Grignard reagent were used per one mole of tri-n-butylborate. The borinic acid so formed was isolated by reaction with ethanol amine thus yielding the diphenyl borinic acid, ethanolamine complex ( (C6H5) 2 BO.CH2CH2NH2) which is easier to handle.

The melting point of the complex was 192-1940C.

PreDaration of 2-nahthvlethvlboronic acid 2-vinylnaphthalene (0.05N) was dissolved in dichloromethane (50ml). Dichloroborane dimethyl sulphide complex (5.8ml, 0.05M) was then added to the 2-vinylnaphthalene solution with stirring. The reaction mixture was refluxed for four hours.

The mixture was then hydrolysed with distilled water (100ml) and the organic layer was separated and dried over magnesium sulphate. The dichloromethane layer was removed by rotary evaporation. The residue so formed was dissolved in hot toluene. Upon cooling, crystals of 2-naphthylethylboronic acid were isolated.

Example 1 The efficacy of biocidal compositions according to the invention against the subterranean termite Retiulitermes santonensis was compared with compositions comprising sodium octaborate (Na2B8013.4H20)., which is a well known boroncontaining wood preservative.

Treatment solutions, containing a range of concentrations between 0 and 1% by weight of sodium octaborate or phenylboronic acid, were applied to filter papers by spread addition of 1 ml of treatment solution. 20 worker termites were then placed in each of several petri dishes containing a water moistened filter paper treated to one of a number of concentrations of either sodium octaborate or phenylboronic acid. The filter papers were checked daily at which time dead termites were removed and the filter paper re-moistened with water as necessary.

Representative results are shown in Table 1.

Table 1 Mortality %

Time | Sodium octoborate Phenylboronic acid (burn) 1.0% 0.1% 1.0% | 0.1 % solutions Solution Solution* Solution 0 0 0 0 0 0 0 0 0 24 0 0 0 0 100 100 0 0 48 0 0 0 0 20 10 72 6.7 0 0 0 60 6.7 96 20 13.3 0 0 93.3 100 120 26.4 26.7 6.7 0 100 144 40 26.7 6.7 0 168 66.7 33.3 6.7 0 336 100 100 86.7 93.3 504 | | | 100 | 100 * 0.55% wt/wt in paper 0.055% wt/wt in paper Example 2 Malt extract/agar (40g/20g) solid media containing a phenyl or substituted phenyl boronic acid at various concentrations were used to assess the growth of representative decay fungi.

Test plates containing the solid media were inoculated with 8mm plugs of actively growing Coniophora puteana (cp) or Coriolus vesicolor (cv) fungi and incubated at a temperature of 220C.

Radial growth was observed over a period of 23 days. Results are shown in Table 2.

Table 2 - Action of Boronic Acids on Fungal Growth

CONCN. GROWTH MM GROWTH MM GROWTH MM GROWTH MM GROWTH MM GROWTH MM GROWTH MM DAY 6 DAY 7 DAY 13 DAY 15 DAY 17 DAY 21 DAY 23 COMPOUND % CP CV CP CV CP CV CP CV CP CV CP CV CP CV Phenylboro- 0.056 - - 1 1 10 1 13 1 17 127. 1 32. 1 nic acid 5 5 0.063 - - - 1 7 1 10 1 15 1 21 1 26 1 p-Chloro 0.052 - - - 1 - 1 - 1 - 1 - 2 - 2 phenyl boronic acid 0.062 - 2 - 4 - 4 - 4 - 4 - 2 - 2 0.072 - - - 2 - 2 - 2 - 2 - 2 - 2 0.080 - - - 1 - 1 - 1 - 1 - 1 - 1 p-Fluoro- 0.048 - - - - - 1 - 1 - 1 - 1 - 1 phenyl boronic acid 0.056 - 1 - 2 - 2 - 3 - 3 - 3 - 3 0.064 - - - - - 2 - 2 - 2 - 1 - 1 0.073 - - - - - 1 - 1 - 1 - 1 - 1 p-Bromo- 0.071 - - - - - 2 - 2 - 2 - 2 - 2 phenyl boronic acid 0.081 - - - - - 9 - 1 - 1 - 1 - 1 0.090 - - - - - 1 - 1 - 1 - 1 - 1 0.102 - - - - - 1 - 1 - 1 - 1 - 1 Sodium 0.0312 6 16 11 21 46 65 58 F 68 F F F F Octaborate Comparison 0.07 2 15 5 20 14 44 17 60 64 75 72 F F F CONTROL - 24 50 30 52 70 F 76 F F F F F F F F = Fully colonised, CP = Coniophora puteana, CV = Coriolus vesicolor

Claims (10)

1. CLAIMS 1. A liquid biocidal or preservative composition which is enzyme free and comprises, (i) as active ingredient at least one organoboron compound of formula (I), (II) or (III),

   in which formulae R1 and R3, which may be the same or different, each represents an optionally substituted alkyl, cycloalkyl, aralkyl or aryl group of up to 20 carbon atoms, which can have a monocyclic or fused ring structure of up to 18 ring carbon atoms, an optionally substituted heterocyclic group containing at least one nitrogen, oxygen or sulfur heteroatom, which can have a monocyclic or fused ring structure of up to 17 ring carbon atoms, or an optionally substituted quinoid group, which can have a monocyclic or fused ring structure of up to 18 ring carbon atoms, R2 and R4, which may be the same or different, each represents a divalent group of the formula

   wherein each X, which may be the same or different, is hydrogen, optionally substituted alkyl of up to 6 carbon atoms, optionally substituted aryl, hydroxy or a derivative thereof, halogen, optionally substituted amino, nitro, thiol or a derivative thereof, aldehyde, carboxylic acid or salt or ester thereof, sulphonate or phosphorate, and o, p and q are each 0, 1 or 2, and m and n, which may be the same or different, are each zero or 1, or a salt of such an organoboron compound; (ii) at least one surfactant; and (iii) an aqueous or organic solvent or carrier.
2. 2. A composition according to claim 1 wherein said organoboron compound is of formula (I) or (II) in which m and n are each zero and R1 and R3, which may be the same or different, are each an optionally substituted group selected from alkyl of up to 10 carbon atoms, cycloalkyl of up to 8 carbon atoms, aryl of up to 12 carbon atoms, aralkyl of up to 16 carbon atoms wherein the aryl moiety has up to 12 carbon atoms and the alkyl moiety has up to 4 carbon atoms or a nitrogen- or sulphur-containing heterocyclic group.
3. 3. A composition according to claim 2 wherein R1 and R2 are each an optionally substituted group selected from n-alkyl of up to 10 carbon atoms, cyclohexyl, phenyl, naphthyl, benzyl, phenylethyl, phenylpropyl, diphenylethyl or thiophenyl.
4. 4. A composition according to claim 1, 2 or 3 wherein the optional substituents are at least one atom or group selected from halogen, C1-C4 alkyl, Cr-C4 alkoxy and trifluoromethyl.
5. 5. A composition according to claim 1 wherein the organoboron compound (i) is any such compound identified herein.
6. 6. A composition according to any one of the preceding claims wherein the surfactant is a cationic, anionic or non-ionic surfactant.
7. 7. A composition according to any one of the preceding claims in the form of an emulsion or microemulsion.
8. 8. A composition according to any one of the preceding claims which contains up to 10% by weight of the organoboron compound (i).
9. 9. A composition according to claim 8 which contains 0.1 to 1% by weight of the organoboron compound (i).
10. 10. A method of treating a porous cellulosic substrate, especially timber, to protect it from deterioration caused by insects, fungi or bacteria which comprises impregnating said porous substrate with a liquid composition as claimed in any one of the preceding claims.