Method of controlling the growth of bacteria and fungi using substituted tetrahydro-s-triazin-2(1H)-one compounds

A method of controlling the growth of bacteria and fungi by applying to the environment inhabited by them a compound represented by the formula ##STR1## where R and R' are hydrogen, methyl, hydroxymethyl or ethyl and can be the same or different.

BACKGROUND OF THE INVENTION 
This invention relates to a method of controlling the growth of bacteria 
and fungi. In a particular aspect, this invention relates to a method of 
controlling the growth of bacteria and fungi by applying thereto, and to 
the environment inhabited by them, certain members of the class of 
triazones. 
Although many anti-bacterial and anti-fungal agents are known, many of the 
previously-used ones have been found to have disadvantages, such as lack 
of stability, ability of the organism to develop resistance, contribution 
to environmental pollution, development of toxic reactions by individuals 
inadvertently exposed to them, etc. Accordingly, there is an ever-present 
need for new anti-bacterial and anti-fungal agents. 
SUMMARY OF THE INVENTION 
It is an object of this invention to provide a method of controlling the 
growth of bacteria and fungi. 
It is another object of this invention to provide a method of controlling 
the growth of bacteria and fungi by applying thereto, and to the 
environment inhabited by them, certain members of the class of triazones. 
Other objects of this invention will be apparent to those skilled in the 
art from the disclosure herein. 
It is the discovery of this invention that the growth of many bacteria and 
fungi is controlled by applying to them, or to the environment inhabited 
by them, a triazone represented by the formula (I) 
##STR2## 
where R and R' can be hydrogen, methyl, hydroxymethyl, or ethyl and can be 
the same or different. 
DETAILED DISCUSSION 
The compounds used in the practice of this invention are prepared by 
reacting dimethylol urea, which is a known compound, commercially 
available, with an alkanolamine represented by the formula 
##STR3## 
where R and R' have the same meanings defined above, and condensing the 
product so obtained with formaldehyde to yield a compound represented by 
formula I, above. The preferred compound is that obtained from 
2-amino-2-methyl-1-propanol. 
Suitable alkanolamines represented by the above formula include 
ethanolamine, 2-amino-propanol, 2-amino-2-methyl-1-propanol, 
2-amino-1-butanol, 2-amino-2-methyl-1,3-propanediol, 
2-amino-2-ethyl-1,3-propanediol, and 
2-amino-2-hydroxymethyl-1,3-propanediol. These alkanolamines are all 
commercially available and the usual commercial grades are suitable for 
the practice of this invention. 
In general, the compounds are prepared by reacting dimethylol urea with the 
alkanolamine in a mole ratio of about 1:1. The reaction proceeds at room 
temperature, but should be heated to about 95.degree. -100.degree. C to 
finish it. The product is then stripped of volatiles at reduced pressure, 
e.g. 50.degree. at 20 mm. It is then cooled to room temperature and 2 
moles of formaldehyde are added. Condensation proceeds at room 
temperature, but heat can be applied to accelerate the reaction if 
preferred. The product so obtained is usually in aqueous solution (if 
aqueous formaldehyde is used) and the solution is suitable for use in the 
practice of this invention. 
The formaldehyde used in the practice of this invention is preferably the 
ordinary 37% aqueous formaldehyde of commerce. However, the 44% grade is 
equally useful as are the solutions of formaldehyde in the lower alkanols. 
Formaldehyde from a formaldehyde source can also be used if desired. 
The compounds of this invention can be used in any manner known in the art, 
of which there are many. Generally they will be used in aqueous systems as 
preservatives, e.g. in cutting oils, protein adhesives, latex paints and 
the like. When preferred, however, they can be applied in the form of 
dusts, sprays and the like. 
The compounds useful in the practice of the present invention are generally 
effective within the range of about 50-2000 ppm or more. Depending on the 
degree of infestation and the organism anticipated, it is generally 
preferred to employ the compounds at the higher concentrations of 
1000-3000 ppm. 
The invention will be better understood with reference to the following 
examples. It is understood, however, that the examples are intended only 
to illustrate the invention, and it is not intended that the invention be 
limited thereby.

EXAMPLE 1 
Dimethylol urea was prepared by delivering to a reaction vessel 60 g of 
urea (1 mole) and 162 g of 37% aqueous formaldehyde (2 moles). The 
reaction vessel was fitted with an agitator and thermometer. The pH was 
adjusted to 7.0 with sodium hydroxide. The mixture was stirred well, then 
allowed to stand at room temperature for about 3 hours. Then 89 g of 
2-amino-2-methyl-1-propanol, 1 mole, was added while maintaining a 
temperature of 5.degree. -15.degree. C. The mixture was then allowed to 
warm slowly to room temperature where it was maintained about an hour. It 
was then heated at 95.degree. -100.degree. C for about 2 hours. Volatiles 
were stripped by vacuum distillation until the pot temperature reached 
50.degree. at 20 mm. 
The reaction mixture was cooled to room temperature and 162 g of 37% 
formaldehyde (2 moles) was added. It was agitated for about 3 hours at 
room temperature and allowed to stand overnight. The resulting product 
contained about 64% of 
tetrahydro-1,3-bis(hydroxymethyl)-5-(2-hydroxy-1,1-dimethylethyl)-1,3,5-tr 
iazin-2(1H)-one in water. 
The compound was tested for anti-bacterial and anti-fungal activity by 
determining the minimum inhibitory concentration range for 9 bacterial and 
8 fungi. In the range given below, the lower figure is the highest 
concentration at which growth occurred and the higher figure is the lowest 
concentration tested at which no growth of organism occurred. The results 
are as follows: 
Minimum Inhibitory 
Bacteria Concentration, ppm 
______________________________________ 
Bacillus subtilis 500-1000 
Staphylococcum aureus 
500-1000 
Streptococcus faecalis 
1000-2000 
Sarcina lutea 1000-2000 
Escherichia coli 1000-2000 
Aerobacter aerogenes 1000-2000 
Pseudomonas aeruginosa 
500-1000 
Salmonella typhi 250-500 
Desulfovibrio aestuarii 
500-1000 
Minimum Inhibitory 
Fungi Concentration, ppm 
______________________________________ 
Cladosporium herbarum 
1000-2000 
Cephalosporium species 
32.25-64.5 
Trichophyton mentagrophytes 
125-250 
Aspergillus niger 500-1000 
Aureobasidium pullulans 
500-1000 
Fusarium moniliforme &gt;2000 
Saccharomyces cerevisiae 
64.5- 125 
Candida albicans 125-250 
______________________________________ 
It is determined that the product is useful as a preservative in latex 
paints and cutting oils. 
EXAMPLE 2 
The experiment of Example 1 is repeated in all essential details except 
that ethanolamine is substituted for 2-amino-2-methyl-1-propanol on an 
equimolar basis. The product obtained is 
tetrahydro-5-(2-hydroxyethyl)-1,3-bis 
(hydroxymethyl)-1,3,5-triazin-2(1H)-one. It is effective as a preservative 
at concentrations of 500 ppm to 3000 ppm or more. 
EXAMPLE 3 
The experiment of Example 1 is repeated in all essential details except 
that 2-amino-1-butanol is substituted for 2-amino-2-methyl-1-propanol on 
an equimolar basis. The product obtained is 
tetrahydro-1,3-bis(hydroxymethyl)-5-[1-(hydroxymethyl)propyl]-1,3,5-triazi 
n-2(1H)-one. It is effective as a preservative at concentrations of 500 ppm 
to 3000 ppms or more. 
EXAMPLE 4 
The experiment of Example 1 is repeated in all essential details except 
that 2-amino-2-methyl-1,3-propanediol is substituted for 
2-amino-2-methyl-1-propanol on an equimolar basis. The product obtained is 
tetrahydro-1,3-bis 
(hydroxymethyl)-5-[1,1-bis(hydroxymethyl)ethyl]-1,3,5-triazin-2(1H)-one. 
It is effective as a preservative at concentrations of 500 ppm to 3000 ppm 
or more. 
EXAMPLE 5 
The experiment of Example 1 is repeated in all essential details except 
that 2-amino-2-ethyl-1,3-propanediol is substituted for 
2-amino-2-methyl-1-propanol on an equimolar basis. The product obtained is 
tetrahydro-1,3-bis(hydroxymethyl)-5-[1,1-bis(hydroxymethyl)propyl]-1,3,5-t 
riazin-2(1H)-one. It is effective as a preservative at concentrations of 
500 ppm to 3000 ppm or more. 
EXAMPLE 6 
The experiment of Example 1 is repeated in all essential details except 
that 2-amino-2-hydroxymethyl-1,3-propanediol is substituted for 
2-amino-2-methyl-1-propanol on an equimolar basis. The product obtained is 
tetrahydro-1,3-bis(hydroxymethyl)-5-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl 
]-1,3,5-triazin-2(1H)-one. It is effective as a preservative at 
concentrations of 500 ppm to 3000 ppm or more. 
EXAMPLE 7 
The experiment of Example 1 is repeated in all essential details except 
that 2-amino-1-propanol is substituted for 2-amino-2-methyl-1-propanol on 
an equimolar basis. The product obtained is 
tetrahydro-1,3-bis(hydroxymethyl)-5-(2-hydroxy-1-methylethyl)-1,3,5-triazi 
n-2(1H)-one. It is effective as a preservative at concentrations of 500 ppm 
to 3000 ppm or more.