GB2203145A - Biocidal allene thiocyanates - Google Patents

Abstract

Compounds of the general formula R<1>R<2>C=C=CR<3>SCN can be used as biocides. Compounds of this type are generally effective against both bacteria and fungi and can be used as a cutting fluid preservative, a wood preservative, in cooling water applications or as an antimicrobial agent in a paint. Certain of the compounds such as 1-thiocyanato-3- bromoallene and 1-thiocyanato-3-iodoallene are new and have a particularly useful combination of properties.

Description

COMPOUND, PROCESS AND USE The present invention relates to a class of chemical compounds, some of which are new compounds, which are useful as industrial biocides.

Allene thiocyanates have been mentioned in the literature for example in Annalen (1969) 721, 121-8 and Monatschefte fur Chemie (1968), 99, 412-428, both of which disclose alpha propyl allene thiocyanate. The latter document- also discloses the preparation of alpha propyl allene thiocyanate derivatives which are substituted in the gamma position with an ethyl group or with both an ethyl group and chlorine, and also notes the derivative substituted in the gamma position with two methyl groups but states that this compound could not be isolated. In Tetrahedron Letters (1980), 21, 3617 to 3620 there is described the use of (CH3)2C=C=CHSCN in the preparation of a tetramethylbicyclodithiaoctane, the allene compound being obtained by reaction of alpha, alpha-dimethylpropargyl bromide with thiocyanate anion.No antimicrobial activity of such thiocyanato-allene compounds seems to have been reported.

We have now found that thiocyanato-allene compounds have useful antimicrobial activity. Certain useful compounds of this type are novel.

According to the present invention there is provided a biocide composition which contains at least one compound of the formula: R 1R2 C=C=CR3SCN wherein: R1 and R2 are independently hydrogen, halogen, a hydrocarbyl group, 1 2 or a substituted hydrocarbyl group, or R1 and R2 together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

If any one or more of the groups R, R and R is a hydrocarbyl group, it can be an alkyl, cycloalkyl, aralkyl or aryl group. The hydrocarbyl group typically contains no more than 20 carbon atoms, for example not more than 10 carbon atoms.

12 3 If any one or more of the groups R , R and R3 is a substituted hydrocarbyl group, it can be a substituted alkyl, cycloalkyl, aralkyl or aryl group. The substituents can be, inter alia, hydrocarbyl groups, ester (that is acyloxy) groups, halogen atoms, nitrile groups or ether groups, which may themselves be substituted. If the hydrocarbyl group is substituted with halogen atoms, it can contain more than one halogen atom, for example as in a trifluoromethyl group.

If R and R together form an unsaturated ring, the ring is conveniently a cyclohexane ring.

Preferred compositions in accordance with the present invention are those containing an allene compound in which R is, or contains, a halogen atom, and R and R are both hydrogen. The preferred compositions have a combination of particularly good anti-bacterial activity and anti-fungal activity. Especially preferred compositions are those in which RI is a halogen atom, for example bromine. Such compositions have activity against bacteria, fungi and algae.

The compositions of the present invention provide good wet state preservation making the compositions advantageous for use as a cutting fluid preservative and also in cooling water applications.

Wood and leather preservation is another advantageous field of application of the compositions. The compositions of the present invention can also be incorporated into paint, as a paint film fungicide that can be used, in contrast with at least some commercially available antimicrobial compounds, without addition of a bactericide.

The compositions containing the allene derivatives may also be used to inhibit the growth of micro-organisms in agricultural and horticultural environments such as living plants, seeds and the like.

The allene derivatives which are present in the composition of the present invention are soluble in many polar solvents, although the solubility is dependent on the nature of the groups R1, R2 and R3. However, many of the allene derivatives are soluble in water, alcohols, ethers, ketones and other polar solvents or mixtures thereof.

The compositions of the present invention may consist only of the allene derivative. However, typically the composition comprises the allene derivative as a solution, suspension or emulsion in a suitable liquid medium such as water. The composition may comprise a suspension or emulsion of the allene derivative, or a solution thereof, in a liquid medium in which the allene derivative is insoluble.

The composition may be incorporated into the medium to be protected using any suitable mixing technique. The composition is incorporated into the medium to be protected in an amount to provide from 0.0001 to 5%, preferably from 0.0005 to 1%, by weight of the allene derivative relative to the total composition. The quantity of the allene derivative present depends upon the nature of the medium, the micro-organism against which protection is required, and the extent of protection desired, for example biostatic or biocidal.

If the composition is being used to preserve a solid substrate such as leather or wood, the composition may be applied directly to the substrate or may be incorporated into a coating composition such as a paint, varnish or lacquer which is then applied to the substrate.

Alternatively, the solid material may be impregnated with the composition of the present invention.

The compositions of the present invention can be used for the treatment of various media to inhibit the growth of microorganisms.

Thus, 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 an allene derivative as hereinbefore defined.

The allene derivatives can be used in conditions in which micro-organisms grow and cause problems such as, for example, in aqueous environments including cooling water systems, paper mill liquors, metal working fluids, geological drilling lubricants, polymer emulsions, and emulsion paints. The allene derivatives can also be used to impregnate solid materials such as wood or leather or can be coated onto the surfaces thereof directly or incorporated into a paint, varnish or lacquer. The allene derivatives may also be used in agricultural or horticultural environments to inhibit the growth of micro-organisms, for example on living plants, seeds and the like.

As a yet further aspect of the present invention there are provided new allene derivatives of the formula:

wherein: R1 and R2 are independently a hydrogen, halogen, a hydrocarbyl group or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group; with the provisos that: when R is a propyl group, R and R are not both hydrogen atoms or methyl groups or when either R or R is an ethyl group, the other one of R and R is other than hydrogen or chlorine; and when R3 is hydrogen, R2 is other than a methyl group when R1 is a methyl group.

New compounds in accordance with the present invention include those in which the groups R and R are both hydrogen and the group R is, or contains, a halogen atom. The group R can be a halocarbon group such as a chloromethyl, bromomethyl or trifluoro-methyl group but is preferably a halogen atom, for example bromine.

The compounds in accordance with the present invention typically show both anti-fungal activity and anti-bacterial activity.

A compound having useful antimicrobial activity is 1-thiocyanato3-bromoallene.

The allene derivatives may be prepared by known procedures, for example as noted in Tetrahedron Letters (1980), 21, 3617 to 3670 and as generally described in J.Am.Chem.Soc. (1967), 89, 622 to 630.

A convenient method of preparing the allene derivative is by the reaction of the corresponding propargyl halide with an alkali metal thiocyanate or ammonium thiocyanate.

More specifically, the allene derivative may be obtained by reaction of a propargyl halide of the general formula: XC 5 CCR 1R2R3 with an alkali metal thiocyanate or ammonium thiocyanate where: R, R and R are as hereinbefore defined; and X is a halogen atom.

The reaction may be effected in any suitable solvent such as, for example, a lower alkanol; an aqueous lower alkanol; a ketone such as acetone; N,N-dimethylformamide; cellosolve and diglyme. By "lower" alkanol or "lower" alkyl is meant a saturated aliphatic group containing not more than six carbon atoms.

The reaction is preferably effected at a relatively low temperature, for example, not more than 80"C, which may be ambient temperature or below for example 150C. If the reaction is effected at a temperature above ambient temperature, it is conveniently effected in acetone under reflux, that is at a temperature between 55 and 60or.

Some propargyl halides, for example propargyl bromide and propargyl chloride are commercially available materials. However, if desired, the desired propargyl halide can be obtained by the reaction of the corresponding alcohol with a halogenating agent, such as, for example phosphorus' tribromide, phosphorus pentachloride, and thionyl chloride. The reaction is preferably effected in the presence of a base, particularly an organic base such as pyridine.

The halogenating reaction is preferably effected in a liquid medium which is a solvent for the alcohol and preferably also for the halide product. The reaction is preferably effected at a temperature not exceeding 80 C and especially not exceeding 50 C. Conveniently the reactants are mixed at a temperature which is initially below ambient temperature, for example from 0 C to 100C.

The halide may be purified before reaction with the thiocyanate compound but allene thiocyanates can be obtained by reaction of an alkali metal or ammonium thiocyanate with the halide reaction mixture, without isolating and purifying the halide.

The desired allene thiocyanate can be isolated and purified using any suitable technique. Thus, the allene thiocyanate may be recrystallised from a suitable solvent or solvent mixture, for example from a mixture of methylene chloride and a low boiling petroleum ether fraction. Alternatively, the allene thiocyanate may be purified by a chromatographic technique, for example by flash chromatography.

Further aspects of the present invention are described in the following illustrative examples in which parts and percentages are by weight for solids or by volume for liquids unless otherwise indicated.

In the following examples, the products obtained were subjected to microbiostatic evaluation and some products were also subjected to microbiocidal evaluation. The microbiological testing was effected, under sterile conditions throughout, as follows: In the microbiological testing, the products were tested for anti-microbial activity against bacteria and/or fungi. The bacteria used were one or more of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The fungi used were one or more of Aspergillus niger, Aureobasidum pullulans, Cladosporium sphaerospermum, Aspergillus versicolor, and Chaetomium globosum.

These test organisms will be referred to hereafter as EC, SA, PA, AN, AP, CS, AV and CG respectively.

Microbiostatic evaluation The material to be tested was dissolved in a suitable solvent and the solution obtained diluted with a further quantity of the same solution 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. The test plates either were inoculated with fungi and incubated at 250C for five days or were inoculated with bacteria and incubated for 24 hours at 370C.

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-organism was recorded.

Microbiocidal Evaluation The product to be tested was added to sterile distilled water to give various concentrations of the product. The flasks were equilibrated to 370C in a shaking water bath. A sample of a culture of EC was added to give an initial test inoculum of about 107 CFU/cm3.

After periods of one hour and four hours, viable survivors were enumerated by pour plate technique. The test plates were incubated at 370C for 48 hours and the number of colonies which developed were counted. The concentration of product which gave a four decimal reduction (that is 99.99% kill) compared to a control flask, which did not contain the product under test, was noted. Example 1 7.7 parts of bromopropargyl chloride (prepared according to JACS (1954), 76, 289) having an infra-red spectrum containing a -1 -1 strong peak at 2210 cm (acetylene group) and no peak at 1960 cm (allege group), and 3.8 parts of ammonium thiocyanate were stirred under reflux in acetone (100 parts) for 2 hours.The reaction mixture was screened and evaporated to dryness using a rotary evaporator at a bath temperature of below 40"C with a vacuum obtained using a water pump. The residue was flash chromatographed on Kiselgel G (a product from Merck GmbH of Darmstadt, Germany) elution being effected using mixtures of petroleum ether (b.pt. 60-800C) with increasing proportions of chloroform. Petroleum ether (65% by volume) and chloroform (35% by volume) eluted the 1-thiocyanato3-bromoallene as an almost colourless oil. The infra-red spectrum obtained using a thin film of the oil, showed absorption peaks at -1 -1 2150 cm (SCN) and 1950 cm (C=C=C). However, the spectrum did -1 -1 not contain peaks at 2220 cm (triple bond) or 2050 cm (-NCS).

Proton magnetic resonance using CDCl3 as solvent and tetramethylsilane as internal reference showed singlet peaks at a delta value of 4.35 ppm and 7.0 ppm, both of these resonances being characteristic of single hydrogen atoms.

By analysis the following composition was found: C 26.7% wt; H 0.6% wt; N 7.5% wt; Br 45.8% wt and S 18.5% wt.

C4H2BrNS requires: C 27.3% wt; H 1.1% wt; N 8.0% wt; Br 45.5% wt and S 18.2% wt.

Example 2 The compound of Example 1 was evaluated against a range of bacteria and fungi by the microbiological techniques hereinbefore described.

In microbiostatic evaluation control for the test organisms was obtained at the following levels: EC 1 ppm SA 5 ppm PA 5 ppm AN 1 ppm AP 1 ppm CS 1 ppm AV 1 ppm CG 1 ppm In the microbiocidal evaluation, this compound caused 4 decimal reductions (9999% kill) in the culture of EC in the times, and at the levels, set out hereafter: 1 hour 625 ppm 4 hours 125 ppm Example 3 3.8 parts of potassium iodide, 5.9 parts of iodine and 40 parts of methanol were stirred together for 15 minutes at 150C.

2.8 parts of propargyl bromide (obtained from Fluka) dissolved in 10 parts of methanol were added to the stirred mixture and stirring was continued for a further 10 minutes at 15"C. A solution of 1.6 parts of potassium hydroxide in 10 parts of methanol was added dropwise to the stirred mixture over a period of 15 minutes whilst maintaining the temperature of the reaction mixture at 10 to 130C by a water bath. On completing this addition, the mixture was stirred for a further 20 minutes at 15 C. 2.5 parts of potassium thiocyanate were added in portions and the reaction mixture was stirred for 18 hours allowing the temperature to rise to ambient temperature. The resulting mixture was screened and evaporated to dryness as in Example 1.A sticky residue was obtained which was separated by flash chromatography as in Example 1. 0.4 parts of l-thiocyanato-3-iodo-allene was obtained by elution with a mixture of chloroform (35% by volume) and petroleum ether (b.pt. 60-800C; 65Z by volume). 3 parts of l-iodopropargyl thiocyanate (eluted with a 45% chloroform/55% petroleum ether mixture) were also obtained.

The l-iodo-3-thiocyanatoallene was obtained as a pale yellow gummy solid. The infra-red spectrum (thin film) showed absorption peaks at 3290cm-1 (characteristic of hydrogen bonded to an allene group), 2160cm (thiocyanate) and 1940cm (allene).

This compound was evaluated against a range of bateria and fungi using the microbiostatic evaluation procedure hereinbefore described. Control for all the test organisms (EC, SA, PA, AN, AP, CS, AV and CG) was obtained at 25 ppm. Lower concentrations of the compound were not tested.

Claims (14)

1. A biocide composition which contains at least one compound of the formula: R1R2 C'=C-CR3SCN wherein: R1 and R2 are independently hydrogen, halogen, a hydrocarbyl group, or a substituted hydrocarbyl group, or R and R together form a saturated ring; and 3 R is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

2. A composition as claimed in claim 1 wherein R1 is, or contains, a halogen atom and R and R are both hydrogen.

3. A composition as claimed in claim 2 wherein R is bromine or iodine.

4. A method for inhibiting the growth of micro-organisms on, or in, a medium, which comprises treating the medium with at least one compound of the formula: R1R2C=C=CR3 SCN wherein: R and R are independently hydrogen, halogen, a hydrocarbyl group, or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

5. A method as claimed in claim 4 wherein the medium which is treated is a cooling water system, a paper mill liquor, a metal working fluid, a geological drilling lubricant, a polymer emulsion, a paint, a lacquer, a varnish, leather or wood.

6. A medium which is selected from a cooling water system, a paper mill liquor, a metal working fluid, a geological drilling lubricant, a polymer emulsion, a paint, a varnish or a lacquer, which contains at least one compound of the formula: R1R2C=C=CR3 SCN wherein: R and R are independently hydrogen, halogen, a hydrocarbyl group, or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

7. Leather or wood which has been impregnated or coated with a medium which is, or which contains, at least one compound of the formula: R1R2C=C=CR3 SCN wherein: R and R are independently hydrogen, halogen, a hydrocarbyl group, or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

8. A compound of the formula:

wherein: R and R are independently a hydrogen, halogen, a hydrocarbyl group or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group; with the provisos that: when R is a propyl group, R and R are not both hydrogen atoms or methyl groups or when either R or R is an ethyl group, the other one of R1 and R2 is other than hydrogen or chlorine; and when R is hydrogen, R is other than a methyl group when R is a methyl group.

9. A compound as claimed in claim 8 wherein R is, or contains, a halogen atom and R and R are both hydrogen.

10. 1-thiocyanato-3-bromoallene.

11. 1-thiocyanato-3-iodoallene.

12. A process which comprises reacting a propargyl halide with an alkali metal thiocyanate or ammonium thiocyanate and recovering from the reaction mixture a compound of the formula: R1R2 C-C-CR3SCN wherein: R1 and R are independently hydrogen, halogen, a hydrocarbyl group, or a substituted hydrocarbyl group, or R and R together form a saturated ring; and R3 is hydrogen, a hydrocarbyl group or a substituted hydrocarbyl group.

13. A process as claimed in claim 12 wherein bromopropargyl chloride is reacted with ammonium thiocyanate and l-thiocyanato3-bromoallene is recovered.

14. A process as claimed in claim 12 wherein iodopropargyl bromide is reacted with potassium thiocyanate and 1-thiocyanato3-iodoallene is recovered.