Antimicrobial compounds

Abstract

Provided are compounds which are useful for controlling microorganisms in aqueous or water-containing systems or in systems which are exposed to moisture, including at elevated temperature. The antimicrobial compounds are of the formula I: ##STR00001##
wherein n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and X are as defined herein.

Claims

1. A compound of formula I: ##STR00013## wherein n is 0 or 1; R.sup.1 is linear or branched C.sub.1-C.sub.10 alkyl; R.sup.2 is H, linear or branched C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.8 cycloalkyl, or aryl; R.sup.3, R.sup.4, and R.sup.5 at each occurrence are independently H, linear or branched C.sub.1-C.sub.10 alkyl, or C.sub.3-C.sub.8 cycloalkyl; or R.sup.2 and R.sup.3 together with the carbon to which they are attached form C.sub.3-C.sub.3 cycloalkyl; or R.sup.4 and R.sup.5 together with the carbon to which they are attached form C.sub.3-C.sub.3 cycloalkyl; and X is O or NR.sup.6, wherein R.sup.6 is linear or branched C.sub.1-C.sub.6 alkyl.

2. The compound of claim 1 n is 1, R.sup.2 is aryl and R.sup.3, R.sup.4, and R.sup.5 are each H.

3. The compound of claim 1 wherein n is 0, and R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are each H.

4. The compound of claim 1 wherein X is O.

5. The compound of claim 1 that is: 1,3-bis(3-methyloxazolidin-2-yl)propane; 1,3-bis (3-butyloxazolidin-2-yl)propane; 1,3-bis(3-octyloxazolidin-2-yl)propane; or 1,3-bis(3-methyl-6-phenyl-1,3-oxazinan-2-yl)propane.

6. A method for controlling microorganisms in an aqueous or water-containing system or in a system which is exposed to moisture, the method comprising contacting the system with the compound of claim 1.

7. The method of claim 6 wherein the system is at a temperature of at least 40 C.

8. The method of claim 6 wherein the system is an oil or gas field fluid, paper machine white water, industrial recirculating water, a starch solution, a latex or polymer emulsion, a coating or building product or household product or personal care product which is manufactured at elevated temperature, a plastic, a hot rolling machining fluid, an industrial dishwashing or laundry fluid, an animal biosecurity fluid, or a high level disinfection fluid.

9. The method of claim 6 wherein the system is a fracturing fluid, a drilling fluid, a water flood system, an oil field water, or a produced fluid.

Description

EXAMPLES

Example 1

(1) ##STR00009##

(2) A three neck 50 mL round bottom flask equipped with a stir bar, thermocouple, addition funnel capped with nitrogen inlet and condenser is charged with 3-(methylamino)-1-phenylpropan-1-ol (100%, 8.26 g, 0.05 mols, 2.0 equivalents) and dissolved in 15 mL of ethylacetate. The flask is cooled to approximately 10 C. under ice/water bath. Once the temperature is reached, glutaraldehyde (50%, 5.0 g, 0.025 mols, 1.0 equivalents) is added drop wise over a period of 5-10 minutes. The reaction temperature is maintained by cooling the bath and by controlled addition of glutaraldehyde. After complete addition of glutaraldehyde, the reaction can still be stirred. However, as the reaction mixture warms to room temperature the reaction mixture becomes opaque and solids start forming. The reaction is stopped and the solid filtered through a Buchner funnel and washed thoroughly with pentane. The white powder is dried under vacuum for 1 h. This process results in 1.5 g of white solid (8% yield). The material does not elute in the GC and therefore is characterized by LC-MS. The LC-MS analysis confirms the presence of (1) 1,3-bis(3-methyl-6-phenyl-1,3-oxazinan-2-yl)propane and CI-LC/MS shows [M+H]=395.

Example 2

(3) ##STR00010##

(4) A three neck 50 mL round bottom flask equipped with a stir bar, thermocouple, addition funnel capped with nitrogen inlet and condenser is charged with 2-(butylamino)ethanol (98%, 5.1 g, 0.042 mols, 2.0 equivalents) and the flask is cooled to approximately 10 C. under ice/water bath. Once the temperature is reached, glutaraldehyde (50%, 4.27 g, 0.021 mols, 1.0 equivalents) is added drop wise over a period of 5-10 minutes. The reaction temperature is maintained by cooling the bath and by controlled addition of glutaraldehyde. After complete addition of glutaraldehyde, the reaction can still be stirred but becomes opaque. GC of the reaction mixture shows the presence of the unreacted amine, the mono oxazolidine adduct (4-(3-butyloxazolidin-2-yl)butanal) and the desired compound (2) peaks. The reaction is stopped and the content of the flask dissolved in 25 mL ethyl acetate and washed thrice with 25 mL water. The resulting organic layer is kept under the rotovap to strip off all the solvent. The GC of the stripped off material, still shows the presence of starting amine and the mono oxazolidine adduct (4-(3-butyloxazolidin-2-yl)butanal). At this time, the content is heated to 40 C. to drive the mono adduct to the desired bis oxazolidine. This process results in 4.60 g of crude yellow liquid (73% yield). The GC-MS analysis confirms the presence of (2) 1,3-bis(3-butyloxazolidin-2-yl)propane and CI-GC/MS shows [M+H]=299.

Example 3

(5) ##STR00011##

(6) Compound 3 may be prepared through substantially the same procedure as described in Example 2, using 2-(octylamino)ethanol as the starting amine

Example 4

(7) ##STR00012##

(8) Compound 4 may be prepared through substantially the same procedure as described in Example 2, using 2-(methylamino)ethanol as the starting amine

Example 5

Assay for Biocidal Efficacy

(9) Assay for Biocidal Efficacy at Room Temperature: Glutaraldehyde and Compounds 1 and 4 are tested for biocidal activity against a pool of aerobic organisms at room temperature and against sulfate reducing bacteria (SRB) at room temperature. Tests are performed as follows:

(10) a. Stock preparation. Glutaraldehyde (50% in water) and Compounds 1 and 4 are each dissolved in DMSO to a concentration of 200 mM, which is equivalent to 20,000 ppm of free glutaraldehyde.

(11) b. Aerobic Bacteriaa mixed pool of 6 bacterial species at approximately 510.sup.6 CFU/mL in phosphate buffered saline is distributed into a 96-well plate. Each well receives an independent chemical treatment of the tested compounds at concentrations ranging from 200 ppm to 12 ppm glutaraldehyde. A control treatment of DMSO alone is also included. Each condition is tested in triplicate. After set periods of incubation (1, 4, and 24 h), the number of surviving cells in each well are enumerated by dilution to extinction in a medium containing resazurin dye as an indicator.
c. Sulfate Reducing Bacteria (SRB)SRB testing is performed as for the aerobic bacteria with the following modifications: the species Desulfovibrio longus is tested in anaerobic PBS and the enumeration of surviving cells is performed in a medium containing soluble iron as an indicator.
d. Results: Values indicate minimum the dose needed (in ppm) to achieve 3-log reduction in bacteria levels. n/a indicates the threshold is not met at any of the tested doses. N.D. indicates no data available.

(12) TABLE-US-00002 bacteria 1 hour 4 hours 24 hours type glut 1 4 glut 1 4 glut 1 4 aerobic 26 59 n/a 26 26 200 26 40 200 SRB 89 133 200 18 133 133 <12 N.D N.D.
Compound 1 shows significant biocidal activity against aerobic bacteria at room temperature. Compound 4 has limited activity under these conditions. Both show some activity against SRB, but are not as effective as glutaraldehyde.
Assay for Biocidal Efficacy at Elevated Temperature

(13) Compound 1 is dissolved in DMSO to yield a 200 mM solution such that the glutaraldehyde-equivalent concentration of the stock solution is 20,000 ppm. The bacterial strain Thermus thermophilus (ATCC 27634) is maintained at 70 C. After 24-48 hours of growth, 10 mL of bacterial culture is harvested by spinning in a Beckman-Coulter benchtop centrifuge at 3000 rpm for 15 min. The cell pellet is resuspended in 100 mL of phosphate-buffered saline (PBS) to give approximately 510.sup.5 CFU/mL and aliquoted into 10 mL portions in glass test tubes fitted with screw caps. Samples are equilibrated to 37, 55, or 70 C. for 30 min and then treated with glutaraldehyde or Compound 1 at 50 ppm glutaraldehyde equivalent. The treated samples are returned to their respective equilibration temperatures for 4 h and then enumerated for surviving bacteria. After 24 h, the process is repeated by adding fresh grown bacteria to the samples to re-challenge the biocide. The samples are again enumerated after 4 h.

(14) Results are reported in terms of log kill of treated bacterial populations relative to an untreated control at each temperature. For values listed as >x, actual kill may have been higher but could not be detected by this assay. Compound 1 shows equivalent activity to glutaraldehyde at each temperature tested.

(15) TABLE-US-00003 4 hr 24 hr temperature glut 1 glut 1 37 C. >3 >3 >4 >4 55 C. >3 >3 >3 >3 70 C. >4 >4 >4 >4