DE2255825B2 - MICROBICIDAL AGENTS BASED ON 3-N-AMINOBENZO-1,2,4-TRIAZINE-DI-N-OXIDES (1,4) - Google Patents

Description

in which A represents the radical R, which denotes alkyl having 1-4 carbon atoms, or represents the group COR ¹ , in which R ¹ denotes alkyl having 1-6 carbon atoms.

2. Use of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) according to claim I for combating microbes.

3. Use of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) according to Claims 1 and 2 for the preservation of coating colors.

4. Use of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) according to Claims 1 and 2 for disinfecting water.

5. Use of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) according to claims 1 and 2 for preventing algae growth in water.

6. Use of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) according to claims 1 and 2 for the microbicidal finishing of tissues.

The invention relates to microbicidal agents on the It has been found that the 3-N-aminobenzo-

Based on 3 - N - aminobenzo - 1,2,4 - triazine - di- 1,2,4-triazine-di-N-oxides of the formula N-oxides (1,4).

(D

lh- NH-A

in which A

(a) for the radical R, which is alkyl having 1-4 carbon bicidal properties.

atoms means, or it has also been found that 3-N-amino

(b) for the group COR ¹ , in which R ¹ denotes alkyl having 1-6 carbon atoms, strong microbenzo-1,2,4-triazine-di-N-oxides (1,4) of the formula (1) are obtained when considering compounds of the formula

(Π)

a) with compounds of the formula
RY

(ΠΙ)

in which R has the meaning given above and Y stands for the active group of an alkylating agent which is split off in the alkylation reaction, optionally alkylated in the presence of an acid binder; or
b) with ketene or a compound of the formula

R ¹ —CO — Z (IV)

in which R ^{1 has} the meaning given above and Z stands for the active group of an acylating agent which is split off in the acylation reaction, optionally acylated in the presence of an acid binding agent.

Surprisingly, the new 3-N-aminobenzo-1,2,4-triazine-di-N-oxides ( 1,4) of the formula (1) has a very good microbicidal activity. According to the invention Fabrics thus enrich technology.

If you use 3-aminobenzo-1,2,4-triazine-dibs N-oxide (1,4) and dimethyl sulfate as starting materials, the course of the reaction can be indicated by the following equation are reproduced [process variant a)]:

CH ₁ O

22 55 825 Γ 0 ¹ I. ϊ 0 4th -NHCH ₃ \ / T 0 / ν + KOSO ₂ ■ CH ₃ SO ₂ + KOH -

If you use 3 - aminobenzo -1,2,4 - triazinedi-N-oxide (l, 4) and acetic anhydride as starting materials, the course of the reaction can be as follows Formula scheme are reproduced [process variant b)]:

CH ₃ CO-O-CO-CH ₃

CH ₃ COOH

The starting materials are generally defined by the formulas (11 to (IV)).

Air »alkyl stands for straight-chain or branched alkyl with 1-4 carbon atoms. Examples are methyl, Called ethyl, n- and i-propyl, n-, i- and t-butyl.

The alkyl R ¹ is straight-chain or branched alkyl having 1 to 6 carbon atoms. Examples include methyl, ethyl, n- and i-propyl, n-, i- and t-butyl.

Suitable alkylating agents of the formula (III) are all alkylating agents which carry the radical R and are customarily used in organic chemistry. Preference is given to using compounds in which the active group of the alkylating agent Y, which is split off in the alkylation reaction, represents halogen, such as fluorine, chlorine, bromine and iodine, in particular chlorine, bromine and iodine, that is to say alkyl, alkenyl or Aralkyl halides (with the aralkyl halides having the halogen atom bonded to the alkyl component), e.g. B. methyl iodide, or in which Y door is the - O - SO ₂ - OR ³ group, in which R ^{3 can have} the same scope of meanings as R and in which R ^{3 is} preferably alkyl (as defined for R), ie especially dialkyl sulfates, e.g. B. dimethyl sulfate and diethyl sulfate.

Suitable acylating agents of the formula IV are all ^{acylating agents which carry the radical R 1} —CO and are customarily used in organic chemistry. Preference is given to using compounds in which the active group of the acylating agent Z, which is split off in the acylation reaction, represents halogen, such as fluorine, chlorine and bromine, in particular fluorine and chlorine, that is to say acid halides, e.g. B. acetyl chloride, or in which Z door is the group

- O — CC) -R ⁵

stands, where R ^{5 can have} the same meaning as R ¹ , that is, carboxylic acid anhydrides, e.g. B. acetic anhydride.

The compound of the formula (11) which can be used according to the invention is known or according to known processes can be produced (cf. J. C. M a s ο η and G. T e nn η η ι. J. Chein. Soc. London, B 1970, 711).

It can also be made to your own suggestion by adding Benzofuroxan's formula

is reacted with twice the molar amount Dinatriumcyanid in aqueous methanol at about 20 to about 60 ⁰ C, which precipitated in crude form compound of formula (II) is filtered off, the precipitate is dissolved in water and acidifying the aqueous solution with acetic acid.

The compound of the formula (II) separates out in crystalline form.

The compounds of the formula (III) which can be used according to the invention are known or in general more common. Methods available. Examples are gc-

named:

Methyl iodide,
Ethyl bromide,
i-propyl chloride,
n-propyl iodide,
Dimethyl sulfate,
Diethyl sulfate,
Di-n-propyl sulfate.

The compounds of the formula (IV) are known or can be obtained by generally customary methods will. Examples are:

Acetyl chloride,
Propionyl bromide,
Propionyl chloride,
Butyric acid chloride,
Valeric acid chloride,
Hexanoic acid chloride,
Acetic anhydride,
n-propionic anhydride.

All inert organic solvents are suitable as diluents. These preferably include ether, 7, B. diethyl ether, dioxane and

Tetrahydrofuran, lower alkyl ketones, ζ. Β. Acetone and methyl ethyl ketone, lower dialkyl formamides, ι. B. dimethylformamide, optionally substituted by halogen, lower alkyl or nitro aliphatic surface or aromatic hydrocarbons, e.g. B. methylene chloride, chloroform, carbon tetrachloride, nitromethane, hexane, heptane, benzene, toluene, xylenes, chlorobenzene, dichlorobenzene and nitrobenzene, lower alkyl nitriles, e.g. B. acetonitrile, and heteroaromatic compounds, e.g. B. pyridine. Furthermore, mixtures of these solvents with one another and, in those cases in which the starting compounds used are inert to water, water can also be used in addition. In many cases, an excess of a reactant (ζ. Β. Carboxylic acid anhydride) can also be used as the solvent.

All customary acid-binding agents can be used as acid-binding agents be used. These preferably include alkali and alkaline earth hydroxides, alkaline earth oxides, Alkali and alkaline earth carbonates and hydrogen carbonates and tertiary aliphatic and aromatic Amines and heterocyclic bases. Examples are sodium, potassium and calcium hydroxide, calcium oxide, Sodium and potassium carbonate, sodium and potassium hydrogen carbonate, triethylamine, diaza-bicyclo-nonene, Called diaza-bicyclo-undecene.

The reaction temperatures can be varied over a wide range. In general, between about 0 and about 150 ^° C., preferably between 20 and 100 ^° C., these temperatures can also be exceeded or fallen below.

The reaction can be carried out under normal pressure, but also under increased pressure. In general one works at normal pressure.

When carrying out the process according to the invention, it is expedient to use 1 mol of the Compound of the formula (II) in each case about 1 to about 5, preferably 1 to 2 mol, of the reaction components of the formulas (III) or (IV) and in cases in which an acid is released, additionally about 1 to about 10, preferably 1 to 2 moles, acid binder. The stated molar ratios can be used over a wide range be deviated without the reaction result is significantly impaired.

When carrying out the process according to the invention, the compound of the formula (11) in one Diluent dissolved or suspended and, if necessary, in portions with the second reaction component of the formulas (IU) or (IV) and also given if necessary mixed with the acid binder. The reaction components can be in any order be put together. Usually the end products of the formula (I) separate after a short time, if necessary after evaporation of the diluent, crystalline. You can use the usual methods, z. B. by recrystallization, isolated and purified

will.
The following new active ingredients are mentioned in detail:

.VN-methylamino-benzo-l ^ -triazinedi-N-oxide (l, 4),

iiJiipropionylainino-benzo-lA ^ triazine di-N-oxide (1,4).

nip active ingredients of formula 1 have strong antimicrobial effects. Your effectiveness. in the 7 B on gram-positive and gram-negative strains, the following bacteria families, bacterial genera and bacterial species being named as examples:

Enterobacteriaceae, e.g. B Eschericha, in particular Escherichia coli; Klebsiella, in particular Klebsiella pneumoniae, Enterobacter; Proteus, ^ special Proteus vulgans, Proteus mirabilis, Proteus morganii, Proteus rettgen and Salmonella in particular Salmonella typhi murium, Salmonella enteritidis;

from the family of the Pseudomonadaceae. z. B. Pseudomonas aeruginosa, Aeromonas e.g. B. Aeromonas liquefaciens; Clostndia, e.g. B. Clostridium botulinum, Clostridium tetani; from the family of the Micrococcaceae, e.g. B. Staphylococcus aureus, Staphylococcus epidermid.s; from the family of the Streptococcaceae, e.g. B. Streptococcus pyogenes, Streptococcus faecalis (duck

aufdeT family of the Mycoplasmataceae, e.g. B. Mycoplasma pneumoniae, Mycoplasma arthntidis.

Excellent and broad microbicidal effectiveness the compounds of formula (1) enable wide use as microbicidal agents e.g. Im-preservation of stretch paints, for disinfection '' from WasS in particular as an algicidal agent, and for the antimicrobial finishing of textile

SNÄthy

di-N-oxide (l, 4),
BNn-Propylamino-benzo-IZ ^ -tria / indi-N-oxide (1.4).
SNi-Propylamino-benzo-lZ ^ -triazinedi-N-oxide (1,4).

Strong microbicidal activity of the compounds of formula (1) is shown by the following examples.

Be i s ρ i e 1 A

Microbicidal effect / reciprocal germ inhibition values

The strong microbicidal action of the compounds of the formula I is selected below on a few Species from the 3 groups bacteria, yeast and fungi compared to the known disinfectant Pentachlorophenol shown in the sprout inhibition test performed after the usual dilution method as follows was carried out:

The microorganisms used for the inhibition test are widespread and compared to conventional, chemical preservatives and disinfectants known to be resistant.

Table A below shows the preparations tested and the microorganisms used the reciprocal sprout inhibition values are given, d. H. the dilutions of the preparations through Diluent and nutrient substrate in which no germ wax occurs.

Table A.

Active ingredient

Microbicidal Effect Reciprocal Inhibition Wcrtc

Asper- Penicil- l'aecikv Tricho- Candida Saccha- Bact.

gillus lium myces

tcrreus cameru- varioti

new se

17th

Staphylo- pseudo-

phyton albicans romyccs prolcus coccus monas: ichia

mentugro- spec. aurcus cyanca coli

phyles

4000

3,000 3,000

(known)

/ VN _V

i Y ^N

7000 30000 30000 14000 30000 30000 30000 7 000 7 000 30 000

NH-CO-CH.,

Λ-Ν HCH.,

5 400 23 000 12 000 12 000 23 (HX) 23 000 12 000 5 400 5 4 (X) 23 000

N ,,, 'NH CO - (; 1I,

5 600 22 IXK) 12 (XX) 12 (XX) 22 (XX) 22 000 22 (XX) 22 (XX) 12 (XXI 22 000

Example B.

Microbicidal effect Reciprocal germ inhibition values Preservation of coating colors

The active ingredients were added directly to the coating color: the assessment was made by spreading out the Color after one day, 7 and 14 days on culture media and subsequent incubation. In the following Table 1 shows the active ingredient added in column 1 and the concentration in column 2 of the active ingredient in the coating color in grams per liter, in column 3 the assessment of the after 1, 7 and 14 days streaked color after incubation, where t infestation and - no infestation of the color by microorganisms means.

Table B. Microbicidal effect / preservation of sire oak

Active ingredient

Control (unbundled) ONa

egg

egg

egg

egg

Account depth nil through microorganisms

trniion

In prank

ΓατΙκη

(R / l)

I Tug 7liigcn I4'lugcn

4th

continuation

Active ingredient

10

Con / .cn attack by microorganisms! Ration
in coating colors

( _& l) I day 7 days 14 days

J-NH-CO-CHj

As can be seen from the table, both the 20 micro-

unrelated controls as well as those contained by additional organisms, while after 14 days

Pentachlorophenol treated paint in every white of the test kills all microorganisms

Test infected by microorganisms while they are with a compound of formula I treated paint

Example C
Algicidal effect / disinfection of circulating water

A heavily contaminated by algae circulation water of a cooling tower and an air chamber were washed three times daily 25 cm ³ of a solution of 50 g of the active compounds listed in the following Table C. 50 g per m ethylglycol ^J water was added. The germ reduction can be seen in Table C below.

Table C.

Algicidal effect / disinfection of circulating water

Active ingredient

Germ / ahl / ccm

Alkyl-dimethyl-benzylammonium-

chloride (well-known commercial product) before adding

15 'after addition

-CO-CH,

IS 'after adding

30 'after addition

60 'after addition

120 'also an encore

500 (XX) 2 (XX)

20 20 20 10

NHCH ₁

It's also an encore SO

30 'after adding -

60 'also draw

120 'also encore 2

continuation

Active ingredient

Germ count / ccm

NH-CO-C ₂ H ₅

15 ' after adding 50 30 ' after adding 60 60 ' after adding 60 120 ' after adding 60

Example D

Microbicidal effect /
Antimicrobial finishing of fabrics

Woven fabrics of wool (calculated on the weight of the fabric) behandeil for 30 minutes in an aqueous bath at 5O ⁰ C in the fleets ratio of 1:15 with the addition of 0.1 to 1% of a compound of general formula 1, and then dried .

Textile material that has been treated with active ingredient as described above is 2 × 2 cm cut large pieces and put these pieces on culture media containing Staphylococcus aureus or Trichophylon mentagrophytis.

After incubation for 24 or 72 hours at 30 ° C, the zones of inhibition are measured. In the following Table D shows the inhibition zones in millimeters for unchecked controls as well as for tissue, that with different amounts of 3-N-acctylamino-bcnz-l, 2,4-triazine-di-N-oxide (l, 4) between 0.1 and 1.0 percent by weight based on the fabric treated as described above.

Table D.

Microbiozklc effect / antimicrobial equipment

Example I.

17.8 g (0.1 mol) S-amino-bcnzo-l ^ -triazine-di-N-oxide (1.4) and 15.1 g (0.12 mol) of dimethyl sulfate are suspended in 60 ml of dimethylformamide, respectively solved. A solution of 5.6 g (0.1 mol) of potassium hydroxide in 5 ml of water is added dropwise to this. It takes place an exothermic reaction, whereby the 3-aminobenzo-l, 2,4-triazine-di-N-oxide (l, 4) with blue paint dissolves. After a while the color changes to brown and orange crystals separate from it Solution off. 15 g (78% of theory) of 3-N-methylaminobenzo-1,2,4-triazine-di-N-oxide (1,4) in Form of orange crystals that appear after dissolving from dimethylformamide / acetonitrile at 210 "C melt with decomposition.

Active ingredient

Control (unbchundcH)

% llcmm / oncn aureus 0 in mm Trieho. ment, 0 Slaph. 0 3 3 5 6th 5 0.1 9 7th 0.25 10 0.5 10 0.75 1.0

Example 2

CO-CHj

The manufacture of the invention-based connection The following examples are used to explain the formula I fertilization:

'"" NHCOCHi

17.8 g (0.1 mol) 3-amino-benzo * l, 2,4-triazine-di '· N-oxide (l, 4) are suspended in 100 ml of acetone and dropwise with 10.2 g (0.1 mol) of Bssigsiiurcanhydno added, after 4 hours it is filtered off with suction, and 21 g (96% of theory) of 3-N-acetyltimlnö-bcnzo are obtained. l, 2,4-triazine-di-N-oxide (l, 4) in the form of yellow crystals, which, after dissolving from acetonitrile, melt at 200 ° C. with decomposition.

example

NHCOCH,

From 3-amino-benzo-l, 2,4-triazine-di-N-oxide (l, 4) and The preparation of the starting compounds of

Propionic anhydride is obtained analogously to Example 2 is formula (H) based on the following example

the 3-N-propionylamino-benzo-1,2,4-triazine -di- purifies. N-oxide (1.4) with a decomposition point of 168 C.

Example a

13.6 g (0.1 mol) of benzofuroxan are suspended at room temperature (approx. 20 ° C.) in a mixture of 40 ml of methanol and 40 ml of H ₂ O, and 17.2 g (0.2 mol) of disodium cyanamide are added in portions . The temperature rises to about 50 to 60 ° C and the solution turns blue-violet. The mixture is stirred for 40 minutes at about 6O ¹¹ C and then the precipitate is filtered off with suction from the mother liquor. The precipitate is dissolved in water and filtered, and the filtrate is acidified with acetic acid. 12.5 g of 3-amino-l, 2,4-benzo-triazine-di-N-oxide (l, 4) (71% of theory) separate out in the form of red gold crystals, which at 220.degree Melt decomposition.

The other starting compounds of the formula II according to the invention can be obtained in an analogous manner.

Claims (1)

Patent claims: 1. Microbicidal agent, labeled by a content of 3-N-aminobenzo-l, 2,4-triazine-di-N-oxides (l, 4) of the formula IO NH-A