DE2115549B2 - DIAETHYLENTRIAMINE DERIVATIVES, THEIR PRODUCTION AND USE AS BIOCIDES - Google Patents

Description

The present invention relates to compounds of the general formula 1

R-NH-CH ₂ -Ch ₂ -N-CH ₂ -CH ₂ -NH-R

R ^(I)

in which R is hydrogen, C ₁₂ H ₂₅ - or

> -CH ₁ -ReSt

is, but both a lauryl and a benzyl as well as a hydrogen radical can be present as the radical R must, and their use as bio-silk.

The compound of the formula II may be mentioned as a typical example

C ₁₂ H ₂ JNH-CH ₂ -CH ₂ -NH-Ch ₁ -CH ₂ -NH-CH ₂ - ^ »

Compounds of type III with biocidal activity are known from German patent specification 947 972.

C ₁₂ H ₂₅ NH-CH ₂ -CH ₁ -NH-Ch ₂ -CH ₂ -NH ₂
C ₁₂ H ₂₅ NH - -CH ₂ - CH ₂ - NH -CH, -CH ₂ - NH -CH ₂ COOH

However, these compounds have disadvantages, e.g. B. a clear protein and soap fault and almost complete Loss of effectiveness against certain problem germs such as pseudomonads in the presence of hard water euf.

A compound of the following formula IV is also known from US Pat. No. 2,952,635:

vx // -CH ₂ -NH - CH ₂ -CH ₂ - NH -CH ₂ -CH ₂ - NH ₂

This compound can be used as a corrosion protection agent. This is suitable as a biocidal active substance Compound because of its poor solubility in water and its sensitivity to hard water. protein and anionic detergents, however, do not.

Finally, compounds of the formula V are known from the German Offenlegungsschrift 1,939,921

CoH "NH -CH ₁ -CH ₃ -NH -CH ₁ -CH ₁ -NH-CH.

where chlorine can be in the 2-, 3- or 4-position. These connections are pretty good in themselves biocidal effectiveness, only they are relatively sparingly soluble in water and clearly sensitive to protein and anionic detergents.

In contrast, it has now surprisingly been found that the compounds according to the invention of formula I also readily soluble in hard water and with excellent biocidal activity and, moreover, un-

Cl

are sensitive to the action of Eiwcil and anionic detergents.

To prepare the compound according to the invention fertilize the formula I either first set: Lauryl halide with diethylenetriamine in a molar ratio of 1: 2 to 1: 4 and after separating off ovei Schüssigem diethylenetriamine with Benzylhalogeni um.oder you can reverse the above reaction; first follow a benzyl halide with diethyl chloride

triamine react in a molar ratio of 1: 2 to 1: 4 and continues after excess diethylenetriamine has been separated off with lauryl halide.

The reactions are carried out at temperatures of 80 to 200 ⁰ C, usually 80 to i40'C. carried out in the presence of acid acceptors and possibly in the presence of solvents. As the lauryl halide, lauryl chloride and lauryl bromide can be used. benzyl chloride and benzyl bromide can be used as the benzyl halide.

As acid acceptors, for. B. NaOH. KOH. KiCO ₃ , CaO or excess amine can be used. Suitable solvents are, for. B. n-propanol. Dioxane, ethyl glycol, propylene glycol and xylene. The compounds of the formula 1 according to the invention obtained in the aforementioned way can be purified by vacuum distillation, whereby they are obtained as an almost colorless liquid. If technical purity is sufficient, only the lower-boiling starting and intermediate products can be demolished. The compounds of formula 1 according to the invention are suitable as i) anti-infectious agents on the basis of the aforementioned excellent shadows, in particular in the form of their salts. Fungicide. Algicide and Virucide / I in use in breweries, the non-alcoholic beverage industry. in dairies, slaughterhouses, in the life-saving industry. usern in swimming pools and in hospitals Yi. \.

The salts of the 1 formula compounds according to the invention include the formates, acetates. Tartrates. lactate c. Citrates. Gluconates. Hydrochlorides and nitrates in question. The pH of the aqueous preparations of these salts can be between 3 and 10 in general between 5 and 8.

In addition, the preparations of the compounds according to the invention can also contain water Solvents such as alcohol, n-propanol. iso-propanol. Ethyl glycol, propylene glycol. Contain dimethylformamide and dimethyl sulfoxide.

In addition, solubilizers such as the water-soluble Adducts of ethylene oxide with fatty alcohols, isotridccyl alcohol !, fatty acid glycerides. partial Fatty acid sorbitol ester, iso-octyl and nonyl phenol, and also the copolymers of ethylene oxide and Propylene oxide and ethoxylated fatty amines and fatty acid amides are added with which the inventive Compounds are very well tolerated. Furthermore, thickeners can be used in such preparations such as methyl, hydroxyethyl and carboxymethyl cellulose, polyvinyl alcohol, polyacrylic acid derivatives and polyvinylpyrrolidone, inert fillers such as aluminum oxide, highly dispersed silica, attapulgite, Urea and cane sugar as well as coloring and odorous substances may be included.

The following examples illustrate the preparation of the compounds according to the invention and their preparations as well as the bacteriological properties explained in more detail:

rature stirred. Then it is allowed to cool. The inorganic residue is decanted and fractionated the organic phase in vacuo. After a run of diethyleniriamin go at 110 to 120 "C and 0.1 to 0.2 torr of 162 g of N-benzyl diethylenetriamine corresponding to a yield of 84% of theory as pale yellow Ul.

Elemental analysis for C _n H ₁₉ N ₃ (193): Calculated ... C 63.3, H 9.9. N 21.7%; found C 68.6. H 9.8, N 21.6%.

b) Production of N-dodecyl-, N-benzyl-diethylen-'5 triamine

1 mol of benzyl diethylenetriamine, 0.75 mol of KOH and 1 ml of water are heated to 90 ° C. in a 1-1 four-necked flask equipped with a stirrer, dropping funnel, thermometer and reflux condenser. 0.5 mol of lauryl bromide is added dropwise, the temperature rising to 130.degree. It is then allowed to react for a further 3 hours at this temperature. The inorganic residue is decanted hot, extracted with ethyl glycol and, after the ethyl glycol has been distilled off, the distillation residue is combined with the organic phase in vacuo. Unreacted starting products are then distilled off at 10 "Torr. The distillation residue is distilled in what is known as a molecular distillation apparatus. At heating bath temperatures of 115 to 165 ° C. and pressures of 5 · 10" ² to 10 "Torr 134 g of N-lauryl -. N-Benzyl-diethylenetriamine obtained as a pale yellow oil corresponding to a yield of 74 "o of theory.

Elemental analysis Door C ₂₃ H ₄₃ N, (361.6): Calculated. . . C 76.4. H 12.0. N 11.6 ° ', found .... C 76.2. H 11.9. Nl 1.5 °,

40

Example 2

Production of N-dodecyl-, N-benzyl-diethylenetriamine from N-üodccyl-diethylenetriamine (manufacture from diethylenetriamine and lauryl chloride according to German patent specification 947 9721 and benzyl chloride

3 moles of N-dodecyl diethylenetriamine. 3 moles of NaOH and 2 ml of water are in a 2-1 four-necked flask

heated to 90 C. To this end, 2 moles of benzyl chloride are gradually added dropwise. Provides cooling one ensures that the reaction does not rise above 120.degree. After stirring for a further 3 hours at this temperature, the procedure is continued as in Example 1bl.

55 N-dodecyl-, N-benzyldiethylenetriamine is obtained in a yield of 82% of theory. Boiling range at 122 to 134 C at 0.05 Torr in a thin film evaporator.

Example 1 a) Preparation of N-benzyldiethylamine

4 mol of diethylenetriamine and 1.5 mol of NaOH are in a 2-1 four-necked flask with stirrer, dropping funnel, Thermometer and reflux condenser heated to 80.degree. 1 mol of benzyl chloride is slowly added dropwise, the temperature should not rise above 110 ° C leaves. Then another 3 hours at this temperature

Example 3

Manufacture of a preparation of N-dodecyl-, N-tertiary-diethylenetriamine

H) Parts by weight of N-dodecyl-, N-benzyl-diethylenetriamine. 5 parts by weight of an addition product of 12 mol of ethylene oxide with IMoI isotridecyl alcohol. 30 parts by weight of ethyl glycol. 5 parts by weight of acetic acid and 50 parts by weight of water are

warm to 40 C homogenized. A clear solution which can be diluted with water as desired is obtained.

Example 4

20 parts by weight of N-Dodecyk N-BeJizyl-diethylenetriamine. 20 parts by weight of an addition product of 15 mol of ethylene oxide with 1 mol of nonylphenol. 70 parts by weight of n-propanol. 12 parts by weight of acetic acid and 78 parts by weight of water are homogenized with gentle heating. The result is a light-colored solution that can be diluted with water.

Example 5

5 parts by weight of N-dodecyl-, N-benzyl-diethylenetriamine. 5 parts by weight of an addition product of 10 moles of ethylene oxide and 1 mole of glycerol monolaurate. 4 parts by weight of tartaric acid, 100 parts by weight of ethanol and 386 parts by weight of water result when stirring and heating to 50 C a clear solution with a weak foaming effect.

Example 6

10 parts by weight of N-dodecyl-, N-benzyl-diethylenetriamine. 10 parts by weight of an addition product of 10 moles of ethylnoxide with 1 mole of laurylamine. 15 parts by weight Gluconic acid, 30 parts by weight of propylene glycol and 35 parts by weight of water are under homogenized with gentle heating. A preparation which can be diluted in water and which is strongly algicid is obtained works.

Bacteriological experiments

The bacteriological tests were carried out in accordance with the guidelines of the German Society for hygiene and microbiology, with the difference that in the interest of greater practical relevance Basically, water of 15 German hardness was used to produce the dilutions, unless expressly stated otherwise in the tables below.

A. Bacteriological effectiveness of N-dodecyl-. N-benzyl diethyl triamine in a suspension experiment

A preparation according to Example 3 was used. The pH of the 0.1% active ingredient aqueous dilution was adjusted to 7.

+ = Bacterial growth.

- = no bacterial growth.

Test strain

Staphylococcus.
aurcus!

Pseudomonas
acruginosa

ί conj
■ / entralion <

Kinffektun ^ s / ei! in minutes

ι Ι:

0.1

0.05

0.01

10; 20 i M)

i t

0.005 I. i 0, (X) I I *
j 0.1 I.
- I -
j 0.05 ._ i.

IO Con Action line in ί 1 ._ = _ 1- ⁵ - -> - "Τ" 10 - 1 + -! - - - - Test strain centering I. j - - -1- - -r - in V. - - - 0.05] - -; - - 4- .— - - |
5 Pseudomonas 0.01 + - -r 0.01 aerutiinos.a 0.005 - 0.005 0.001 - y _ 0.001 Proteus 0.1 - - i - ίο vulsaris 0.05 -r "I" j * 0.01 -V 0.005 0.001 ~~ I '5 Escherichia 0.1 coli

20th

30th

B. Bacteriological Effectiveness of a Wreleiehssubstan / serving phenotypes; Tm suspension test, which is composed as follows is:

7.5 parts by weight of o-phenylphenol 2.5 parts by weight of p-chloro-o-benzyl-phenol 7.5 parts by weight of sodium dodecylbenzenesulfonate, 30 parts by weight of ethylene glycol 52.5 parts by weight of water

and so much KOH. that when this preparation containing 10 percent by weight of active ingredient is diluted to 0.1% active ingredient (with water at 15 ° German Hardness) a pH value of 9 results.

Test strain

Staphylococcus aureus

Pseudomonas
aeruginosa

Proteus
vulgaris

Escherichia
coli

Kon-I / enlration

0.1 0.05 0.01 0.005

0.1 0.05 .0.01

0.1 0.05 0.01 0.005

0.1 0.05 0.01 0.005

Exposure time in minutes

M- ² ■

10

20 M)

ft5 When comparing the bacteriological effectiveness of the compound according to the invention and the comparison substance clearly shows the superiority of the compound (1) according to the invention.

C. di:

you ge 'ge:

C. Bacteriological effectiveness of lauryl and benzyl diethylenetriamine in water of 40 ° German hardness

pH value of dilution stage 7 containing 0.1% active ingredient. The dilutions were started out produced from a preparation according to Example 4.

Suspension test

Test lamb

Staphylococcus
aureus

Pseudomonas
aeruginosa

Proteus
vulgaris

Escherichia
coli

Con Action in minutes I. 2 5 10 20! 30th _ - - - - - '■', - - - centralion _ _ _ - - - - - - - - in % - - - - - - - - - 0.1 + - - - - - - 4- 0.05 4- 4- - - - i - ^; ! _ + 0.01 + 4- 4- 4- - i; - 0.005 - - - 4th 0.001 - - ; - 4th 0.1 + 4th r - 0.05 - - - 0.01 - - - 0.1 4- - 0.05 4- 4- 0.01 + 0.005 _ 0.001 - 0.1 - 0.05 - 0.01 4- 0.005 0.001

8th Test lamb Con
centering Exposure time in I. 2 5 10 Out there 30th ί f - 4- in % + + + - 20th ■ - 4- ■ ^s Staphylococcus 0.01 4- + j 4- - aureus 0.005 4- 4- + - 0.001 4- + _ - Pseudomonas 0.5 + 4- 4th 4th 4- ⁰ aeruginosa 0.2 4- + 4th + - 0.1 + 4- -f 4th 0.05 + - - - 4- Proteus 0.5 4- + + + 'vulgaris 0.2 + 4th 4- + 0.1 4th + + ■ 4- 0.05 4- - - - Escherichia 0.1 4th + -f - coli 0.05 ₊ 4- 4- 4- 0.01

When comparing the bacteriological effectiveness in very hard water you can clearly see that Progress of the compound according to the invention (3), that of the comparison substance in the problem germs Pseudomonas and Proteus by the factor

jo S; 10 is superior.

D. Bacteriological effectiveness of a reference substance ir. Water of 40 ° German hardness (reaction product of 1 mole of lauryl diethylenetriamine with 1 mole of chloroacetic acid)

The pH of the aqueous solution containing 0.1% active ingredient was adjusted to 7.

E.a) Bacteriological effectiveness of N-dodecyl-. N-benzyl diethylenetriamine in the presence of 20% Beef crimson

A preparation according to Example 3 was used.

b) A quaternary ammonium compound of the formula

Con
centering _ I. 2 5 J 10 i 20; > <l - '- I - ₅ o 1 2 5 ₄ ΙΟ } 20 _, _ SI 4- - - - CH ₃ Cl ί + _ 5 to 20 30 - - Tesis lamb in % -; - - chosen. - - - + + - j 4- - - - - + - 45 - - - a
Euwulmngszcit in minutes + - - - I - + i + 4- - - - ⁺ 4- 0.1 ^{+ +} + + - j - C ₁₂ H ₂ SN-CH ₂ - / "^ + + + 4- 4- Staphylococcus 0.05 Exposure time in minutes KOQ-
zcniratioo - - 4- '4- + + + + + aureus to * / * + - +! + - CH ₃ ' ^b
j Impact in Kfinutcn 4- + + + 4- + Test »™ αϊ + + _ I _ - t ¹ I- ² - + - + +! - * - 0.05 - -, - + ■ ■ I + + - - - Staphylococcus 0.01 - + + + + + aureos 0.1 _ _ _ 4- + 0.05 + - ^; - + Pseudomonas 0.01 + aerugmosa 0.1 0.05 Escherichia coli 0.01

309 533/54

The comparison of the bacteriological efficacy in white exposure clearly shows the superiority of the compound (5a) according to the invention.

Comparative experiment

The mode of action of hexachlorophene as a disinfectant is described in the book »Sterilization, Disinfection. Conservation, Chemotherapy «by WaIlhaußer and Schmidt, Georg Thieme Verlag. Stuttgart, 1967, p. 193.

As a comparison substance, a mixture of equal parts by weight of hexachlorophene and one Reaction product of 12MoI ethylene oxide used with tridecyl alcohol. The specified concentrations refer to the content of hexachlorophene. The pH of the aqueous solution is 7.7.

Test strain Lmralion! Exposure time in minutes

IO

3d

10 I. Twirki Con Fi ₊ centering EGG + f in % + + 0.01 + f 0.005 - I. 1.0 -t- _ 0.5 + + 2.0 + -t- 1.0 + ₊ 0.5 + 5.0 -i- + 2.5 + ₊ l 1.0 + + 5.0 + 2.5 1.0

Kt i JU j .'I '

1 I.

S. aureus

0.1
0.05

Test strain

S. aureus

E. coli

P. aeruginosa

C. albicans P. expansum The table shows the superiority of the invention appropriate connection with regard to their microbicidal effectiveness.

Claims (3)

Patent claims:
1. Compounds of the general formula R-NH-Ch ₁ -CH ₁ -N-CH ₁ -CH ₁ -NH-R in which R is hydrogen, C ₁₂ H ₂₅ - or -CH.-rest is, however, both a lauryl and a benzyl as well as a hydrogen radical are present as the radical R must be. 2. Process for the preparation of compounds according to claim 1, characterized in that either lauryl halide is reacted with diethylenetriamine in a molar ratio of 1: 2 to 1: 4, the excess diethylenetriamine is separated off and the product is reacted with benzyl halide or benzyl halide with diethylenetriamine in a molar ratio of 1: 2 to 1: 4, the excess diethylenetriamine is separated off and the process product is reacted with lauryl halide, the reactions being carried out in a temperature range of 80 to 200 ^c C and / or in the presence of solvents and / or acid acceptors. 3. Use of the compounds according to claim 1 as disinfectants, preservatives and sanitary cleaning agents.