DE2450707A1 - NEW QUATERNAERE CONNECTIONS AND THESE ORAL CARE PRODUCTS - Google Patents

Description

UEXKULI. & STOLBERG PATENTANWÄLTE

2 HAMBURG 52

BESELERSTRASSE 4

DR. J.-D. FRHR. by UEXKÜLL DR. ULRICH GRAF STOLBERQ

DIPL.-ING. JÜRGEN SUCHANTKE

Colgate Palmolive Co. Prio: February 25, 1974

300 Park Avenue US 445 542, '445 713,

New York 22, N.Y. U.S.A. 445 714-11665

Hamburg, October 23, 1974

New quaternary compounds and oral care products containing them

The invention relates to oral care products and new quaternary ammonium compounds with the following general formula:

⁺ X

in which R is an aliphatic or alicyclic group with 7 to 13

2 3

Carbon atoms, R and R are each a methyl or ethyl radical, R is an aliphatic chain with 10 to 18 carbon atoms, Z is CH ₂ , 0, S, C = O, COO, CONH, CHOH, NHCOO or NHCSO, η is one is an integer from 1 to 3 and X is a compatible anion, such as, for example, the halides such as Cl-, Br-, J-, sulfates such as methyl sulfate, nitrates, aryl sulfonates, etc. These quaternary compounds and the oral care products containing them have excellent activity against Microorganisms, tooth decay and tartar.

509835/1049

_ 2 -

The alicyclic group can be any ring system such as a

3 Adamantane residue, which differs from the tricyclo- (3,3,1, 1, 7) -dekan and, as the following formula shows, consists of four condensed cyclohexane rings:

or a bicyclic (3,3,0) octane with 2 pentane rings joined together :

2 -

or a norbornane residue exhibited by the following ring structural formula

509835/10 ^ 9

OWGSNAL IhJSPECTED

" ³ ■ 24507Q7

or any other aliphatic ring system with 7 to 13 carbon atoms.

Typical examples of quaternary ammonium compounds in which Z in accordance with the invention is a carboxamide residue (CONH), are:

1. S-heptanamidopropyldimethyltetradecylammonium chloride,

2. S-decanamidopropyldimethyltetradecylammonium chloride,

3. S-octanamidopropyldimethyldecylammonium iodide,

4. S-octanamide propyldimethyldodecylammonium iodide,

5. S-octenamidopropyldimethyltetradecylammonium chloride,

6. S-Nonanamidpropyldimethyltetfadecylammoniumchlorid,

7. S-dodecanamidopropyldimethyltetradecylammonium chloride,

8. S-Undecanamidpropyldimethyltetradecylammonium chloride,

9. 3- (Ί'-Adamantancaiboxamid) propyldimethyldodecylammonium bromide,

10. 3 - (1'-Adamantancarboxamid) propyIdimethyltetradecylairanoniumbromid,

11. 3- (1'-adamantane carboxamide) propyldimethyltetradecylammonium chloride,

12. 2- (V-adamantane carboxamide) ethyl diethyl decylairanonium bromide,

13. 2- (1 '-Adamantancarboxamid) äthyIdiäthyldodecylammoniumbromid ,.

14. 3- (exo, cis-bicyclooctane-2-carboxamide) propyltetradecyldimethylammonium bromide,

15. 3- (exo, cis-bicyclooctane-2-carboxamide) propyldodecyldimethylammonium bromide, -

16. 3- (2'-norbornane carboxamide) propyltetradecyldimethylammonium bromide.

Typical examples of quaternary ammonium compounds in which Z is an ether-oxygen and R is adamantane are are:

509835 / 10Λ9

17. 2- (1 "'-Adamantyloxy) ethyldimethyldodecylammonium bromide,

18. 2— (1 '-Adamantyloxy) ethyldimethyltetradecylammonium bromide,

19. 2- (T'-Adamantyloxy) ethyldimethyldecylammonium chloride,

20. 2- {1'-Adamantyloxy) ethyldimethylhexadecylammonium chloride,

21. 2- (1'-Adamantyloxy) ethyldimethyloctadecylammonium chloride,

22. 3- (1'-Adamantyloxy) propyldimethyldodecylammonium bromide.

Typical examples of quaternary ammonium compounds in which R is an adamantane residue and Z is a keto group (C = O), are:

23rd 2-Adamantylcarbonyläthyldimethyldecylammoniumbromid,

24. 3-Adamantylcarbonylpropyldimethyltetradecylammonium bromide,

25. 2-Adamantylcarbonyläthyldimethylhexadecylammoniumbromid,

26. 1-Adamantylcarbonyläthyldimethyloctadecylammoniumbromid,

27. 1 -Adamantylcarbonylmethyldimethyltetradecylammonium bromide,

28. 1-Adamantylcarbonylmethyldimethyldodecylammonium bromide.

Other examples of quaternary ammonium compounds in which, in accordance with the invention, R is an adamantane radical and Z is an ester-forming carboxyl group (COO) or an ester-forming thiocarbamate group (NHCSO) ₇ are:

29. 2— (1 '-Adamantancarbonyloxy) ethyldimethyldecylammonium bromide ,

30. 2— (1'-Adamantancarbonyloxy) ethyldimethytetradecylammonium bromide,

31. 2- (1'-Adamantane carbonyloxy) äthyldime thy ldodecy lammonium bromide ,

32. 2- (1'-Adamanty lthiocarbamyloxy) äthyldime thy ldodecy lammonium bromide,

509835/1049

Other halides and analogous compounds can also be used such as sulfates, nitrates, or aryl sulfonates, among others, can be used as effective bactericides.

It has been observed that those described above generally Compounds particularly effective against gram-positive organisms such as Staphylococcus aureus, Streptococcus mitis, sanguis and mutans, Bacillus subtilis, Corynbacterium acnes, Actinomycetes naeslundii and against fungi such as Candida albicans, Trichophyton mentogrophytes and Aspergillus niger; are moderately effective it against the gram-negative bacteria Escherichia coil. Ver

4th
bonds in which R is a benzyl radical instead of a higher alkyl radical have no antibacterial effect.

The antimicrobial nature of the new compounds of the invention was shown in a standardized dilution series investigation, in which an appropriate number of test tubes with broth in decreasing concentrations the to be examined Compounds contained and inoculated with the test organisms. After sufficient incubation time, the tubes opened Presence or absence of the test organisms examined. The effectiveness of the compounds to be investigated results from the lowest concentration that prevents the growth of the organisms and is called the minimal inhibitory concentration in ppm specified. As the following table of antimicrobial data shows, there is a defined jump between the compounds,

4 4

in which R contains 8 carbons, and those in which R contains 10 carbon atoms.

509835/1049

Table 1

Minde sthemmkonzentration (ppm)

I JeOMICH ₀ CH ₀ N (C ₀ H,.) IT Br

R = C ₄ H _g ^C 6 ^H 13 ^C 8 ^H 17 ^C 1O ^H 21 ^C 12 ^H 25 S. aureus 100 100 25th 3.12 1.56 St. sanguis 50 50 50 6.25 3.12 St. mutans 100 100 25th 6.25 0.78 A. naeslundii 100 50 12.5 1.56 0.39 C. albicans 100 100. 50 6.25 1.56 T. mentagrophytes 50 50 50 50 3.12 A. niger 100 100 100 50 12.5

These dilution tests show the effectiveness of the inventive Compounds against bacteria and fungi, which are amidoquaternary ammonium compounds with 3 lower aliphatic residues not own.

The excellent and surprising antimicrobial effectiveness of the new compounds according to the invention is also evident from the results of antimicrobial tests listed in Tables 2 and 3.

509835/1049 O

_ .. «7"

aureus Tabel 2 25th Verb. 14 Verb. 15 Verb. 16 Link 9 Vb 10 . sanguis Minimum inhibition concentration (ppm) 0.78 1.56 1.56 0.78 0.39 . mitis Link 3 6.25 3.12 1.56 -, - . mutans 12.5 0.39 0.39 microbe naeslundii 6.25 0.05 0.1 0.1 S. coli 0.05 0.19 0.1 St aeruginosa 0.78 50 25th 50 50, O 25.0 St albicans 12.5 50 25th 50 —.— St 50 3.12 3.12 3.12 6.25 6.25 A. 25th 3.12 6.25 6.25 12.5 25.0 E. 6.25 25th 25th 25th 25.0 50.0 P. mentagrophytes 12.5 C. Niger T. A.

Table 3

4 -7

^ RCONH (CH ₂ ) ₃ N (CH ₃ ) ₂ R _ / X

RR X S. aureus S. mitis E. coli C. albicans T. menta- - qrophytes

'11 "Ί
C- (branched)

^C 12 ^τ H ₉ ) (C ₂ H ₅ ) CH

50

50

50

50

'12

C- (branched) ^C 14

'14

'14

Ί4

Ί4

1.56

0.78

3.12 50

1.56 12.5

3.12

1.56

50

12.5

12.5

Cl 0.78 1.56 50 3.12 6.25 Cl 0.78 1.56 50 3.12 3.12 Cl 1.56 0.73 100 1/56 3.12 Cl 3.12 6.25 100 3/12 6.25 Cl 6.25 12.5 100 25th 25th 50983 B / 104 9

The table above shows that the new amidoquaternary ammonium compounds according to the invention with 2 large aliphatic or alycyclic groups have excellent antimicrobial properties that are not to be expected, which the well-known quaternary Ammonium compounds such as compound 1 in Table 3 and the first three compounds in Table 1 do not have.

Table 4

^ Adamanty1-OCH ₂ CH ₂ N (CH ₃ ) ₂ R _ / Br

S. aureus

St. mitis

C. albicans

P. ovale

T. mentagrophytes

Ps. Aeruginosa

A. niger

E. coli

R ⁴ = (

0.78 0.39 1.56

50 6.25

25th

50

12.5

^C 12 ^H 25 0.39 0.19 1.56

50
-3.12

12.5

These dilution experiments prove the effectiveness of the invention, quaternary ammonium compounds containing an ether group against bacteria and fungi.

509835/1049

S. aureus 1.56 T? "" ^ * ¹ DD 5 2 ^r4 -7 ^{+ C} 14 ^H 29 Br " St. mitis 0.78 1.56 ₂ N (CH ₃ ) Z = COO 0.78 B. subtilis 0.39 6.25 ^C 12 ^H 25 0.78 C ₄ H ₉ Tabel Cornybacterium
acne 12.5 1.56 0.02 0.10 100 ^ Adamantyl Z CH ₃ CH C. albicans 6.25 1.56 0.19 25th 100 Z = NIICSO T. mentagrophyte 3.9 12.5 0.19 6.25 100 R. A. niger 62.5 7.8 6.25 25th E. coli 25th 31.2 0.78 50 100 Pr. Aeruainosa ■ M «t * M)« _ 25th 6.25 50 100 50 50 100 12.5 100 100

The above results of dilution tests also show the effectiveness of the compounds according to the invention. Quaternaries

4th
Ammonium carboxyl esters in which R is a lower aliphatic radical such as a butyl radical have no corresponding effectiveness.

To suppress the growth of organisms, lower concentrations of the invention are generally sufficient Compounds than analogous compounds containing essentially the same number of carbon atoms.

809835/1049 O

When using the compounds according to the invention against bacteria or fungi, these can be applied directly to the surface to be protected can be applied or in a pharmaceutical carrier be resolved. Typically, an effective amount, e.g., 0.025% to about 10% by weight, of the compound becomes an inert carrier and given to a dispersing or surface active agent. Alternatively, an effective amount, e.g. 0.025 to 10% by weight in a solid, possibly inert carrier such as talc, clay, diatomaceous earth or flour, among others.

In addition, the quaternary ammonium amides are the adamantane carboxylic acid particularly effective against the formation of tartar or plague. This is shown by the results of experiments with albino rats. 15 male and 15 female rats were fed a Zipkin-McClure diet which produced plaque or tartar. six For weeks, the teeth of each animal were treated with a test solution for 30 seconds a day or, in the case of the control group, with water treated. The animals were then sacrificed and examined for tartar or calculus using the Baer method. the Results were analyzed using the Student's "t" test. It there was a 99% agreement.

Concentration reduction in tartar% Compound of the test solution male female female animals

3- (1'-aamantane 0.1% 43.43 6.27

carboxaniido) propyltetradecyIdimethy1-ammonium bromide

509835/1049

These results show the significant effectiveness of the invention quaternary compounds to prevent tartar formation at concentrations as low as 0.1%.

When the compounds of the invention are intended for use in mixtures which reduce the formation of tooth decay and prevent the formation of tartar, they are usually used in amounts of up to 5% by weight, preferably from 0.25 to 1% by weight and best mixed with the oral care products in amounts of 0.05 to 0.5% by weight. The oral hygiene product is usually a dentifrice Like toothpaste, tooth tablet or tooth powder with about 20 to 95% by weight of a water-insoluble polishing material as a carrier, which preferably water-insoluble phosphates such as dicalcium phosphate, Contains tricalcium phosphate or trimagnesium phosphate. The dentifrice can also contain water, binders such as glycerine, sorbitol, propylene glycol and polyethylene glycol 400, cleaning agents, gelling agents such as carrageen moss or sodium carboxymethyl cellulose, other antibacterial substances, coloring or bleaching agents, protective agents, silicones, chlorophyll compounds, other ammonium-containing materials, flavorings or Contain sweeteners and compounds that provide fluorine-containing ions such as sodium fluoride, stannous fluoride and sodium monofluorophosphate.

The oral care product can also be liquid, such as mouthwash, which is typically 20 to 99% by weight of an aqueous lower aliphatic alcohol, preferably about 11 to 30% by weight alcohol such as ethanol, n-propyl or isopropyl alcohol.

5 09835/1049

Such oral care products are generally used in the following way / that you brush your teeth or rinse your oral cavity at least once a day for 30 to 90 seconds. Typical inventive Oral care products can be used in this way and are described in the following examples.

example 1

Toothpaste

S-decanamidopropyldimethyltetradecylammonium chloride 0.50

Nonionic surfactant; 1.0Q

Glycerin 22.00

Sodium pyrophosphate 0.25

Carboxymethyl cellulose 0.85

Sodium Saccharin "O, 2O

Sodium benzoate 0/50

Calcium carbonate (precipitated) 5/00

Dicalcium phosphate dihydrate 46/75

Flavors 0.80

Water 22.15

Tween 80 polyoxyethylene sorbitol monooleate (20 mole ethylene oxide)

Example 2

Instead of the quaternary ammonium amide chloride in Example 1 were 0.50% 2 (1'-adamantyloxy) ethyldodecyldimethylammonium bromide is used .

§09835 / 1049

Example 3

Instead of the quaternary ammonium amide compound in Example 1 0.50% of a quaternary ammonium adamantyl ketone was used.

Example 4

The quaternary ammonium amide compound in Example 1 was through Replaced 0.50% of an adamantane carboxylic acid ester with a quaternary ammonium compound.

Example 5
Mouthwash

Quaternary ammonium amide of adamantane carboxylic acid 0.025 Nonionic surfactant (Pluronic F-68) ⁺ 1.00.

Ethyl alcohol (containing flavorings) 15.00

Glycerin 10.00 Saccharin O, 02

Water 73.955

Block polymer made from 80% polyoxyethylene and 20% polyoxypropylene.

Example 6

The amide in Example 5 was replaced by 0.05% of a quaternary ammonium adamantyl ketone and the water content accordingly customized.

S09835 / 1049

Example 7

Instead of the amide in Example 5, 0.05% 2- (1'-adamantyloxy) äthyltetradecyldiraethylammoniuinbromid used and the Adjusted water content accordingly.

A preferred component of the mixture according to the invention is a nonionic surfactant that provides an increased prophylactic effect, the careful and complete distribution of the Mixture according to the invention supports in the oral cavity and makes the mixtures according to the invention cosmetically acceptable. That nonionic surfactant not only gives the mixtures cleaning and foaming properties, but also keeps the taste ' substances in solution, i.e. makes the flavor oils soluble. In addition, the nonionic surfactants are fully compatible with the quaternary ammonium compounds according to the invention and deliver such a stable, homogeneous mixture with increased antibacterial effects, anti-caries and anti-tartar effects. The presence an anionic surfactant would reduce the good properties of the quaternary compounds through precipitation and / or Prevent interaction.

The nonionic organic surface-active compounds or surfactants are water-soluble and are condensed an alkylene oxide or equivalent reactant and a hydrophobic, reactive hydrogen-containing compound manufactured. The hydrophobic organic compounds can be aliphatics, aromatics or heterocycles, although the first two classes are preferred.

S09835 / 1049

The preferred hydrophobic compounds are higher aliphatic Alcohols and alkyl phenols; others such as carboxylic acids, carboxamides, mercaptans, sulfonamides, and others can also be used will. The ethylene oxide condensates with higher alkyl phenols are preferred. The hydrophobic compound should usually be at least contain about 6, and preferably about 8 carbon atoms and can contain up to about 50 or more carbon atoms. The amount of Alkylene oxides can vary considerably depending on the hydrophobic compound; in general, at least about 5 moles of alkylene oxide can be used per mole of hydrophobic compound. The upper limit of alkylene oxide also varies, but no particular importance can be ascribed to it. It can have 200 or more moles of alkylene oxide per mole of hydrophobic compound be used. While ethylene oxide is the preferred and predominant alkoxylating agent, others may as well lower alkylene oxides such as propylene oxide, butylene oxide and the like can be used or replace part of the ethylene oxide. Other suitable nonionic compounds are the polyoxyalkylene esters of organic acids such as higher fatty acids, rosin acids, tall oil acids or the acids from petroleum oxidation products. ■ These esters usually contain about 10 to 22 carbon atoms in the acid component and about 12 to 30 moles of ethylene oxide or an equivalent compound.

Other nonionic surfactants are the alkylene oxide condensates i higher fatty acid amides. The fatty acid group generally contains about 8 to 22 carbon atoms and is preferred

509 8 35/1049

condensed with about 10 to 50 moles of ethylene oxide. The corresponding Carboxamides and sulfonamides can also be used.

Another class of nonionic surfactants are the oxyalkylated ones higher aliphatic alcohols. The fatty alcohols should have at least 6 carbon atoms and preferably at least about Contains 8 carbon atoms. Most preferred alcohols are lauryl, myristyl, cetyl, stearyl and oleyl alcohols. the mentioned alcohols are condensed with at least about 6 moles and preferably with about 10 to 30 moles of ethylene oxide. A a typical nonionic surfactant is oleyl alcohol condensed with 15 moles of ethylene oxide. The corresponding with ethylene oxide condensed alkyl mercaptans are also suitable for the mixtures according to the invention.

Depending on the specific properties of the one to be used nonionic surfactant as well as depending on the amounts and properties of the other ingredients in the oral care product In general, the amount of the nonionic surfactant, based on the total weight of the oral care product, can be from about 0.2 to 3.0% by weight can be varied.

The process for the preparation of the quaternary ammonium compounds according to the invention generally consists of two steps. First, a compound containing the RZ radical is combined with a

2 3
the compound containing RR -Arainrest converted to a tertiary amine and this is then quaternized with a higher aliphatic halide,

509835/1049

~ 17 -

The quaternary ammonium amides according to the invention can in one Two-step process can be produced. A carboxylic acid, an ester or an acid chloride is treated with Ν, Ν-dialkylethylenediamine or N, N-dialkyl propylenediamine to a tertiary amino amide and this is then reacted with an alkyl halide or an ester of sulfuric acid or arenesulfonic acid (Methyl p-toluene sulforate) as in the following equations

2 3 4 indicated, quaternized, where R, R, R and R are the above mean specified residues.

o R ² ° R ²

1. RCOH ■ + 'NH ₀ (CH ₀ ). N ^. RC-NH (CH ₀ ) - N + H ₀ O

R ³ R ³

O R

2. RCNH (CH ₀ ) - N + RX

2'3 V R

0 R

RCNH (CH ₀ ) - NO

2'3 V R

The quaternary ammonium esters of adamantane carboxylic acid can also can be prepared in a two-step process by adding adamantane carboxylic acid chloride is reacted with a dimethylaminoethanol to the carboxylate and this is then as in the following Equations given, quaternized with an alkyl halide:

ι.

COCl

HC,

HC

¹ IL

+ HIGH ₂ CH ₀ N

Ot ₁ .

--V.

"2

COOCH ₀ CH,

(ν <ί t

2C

HC

CH.

■ ti.

Sk ci ?,

+ HCl

SO & 835/1049

OWGlNAL INSPECTED

The quaternary ammonium ethers according to the invention can also be prepared in a two-step process by a 1-Haloadarnantan with a Dimethylaminoäthanol to a tertiary amino ether is reacted and then with an alkyl halide or an ester of sulfuric acid or the Arenesulfonic acid (methyl toluenesulfonate) as in the following

4 equations given, is quaternized, where R and R are the The remainders given above mean:

1. RBr +

CH ₃

2. RO (CH ₀ ) _O N + R ⁴ X CH-,

+ H Br

CH ₃ RO (CH ₀ J ₀ -N -R ⁴

Similarly, also.die invention by the quaternary ammonium compounds given in the following formulas:

/ RCO (CH ₂ ) _n N (CH ₃ ) ₂ R ⁴ _7 ⁺ X "/ RNHCSO (CH ₀ ) N (CH_) _O R ⁴ / X / RS (CH ₂ ) _n N (CH ₃ ) 2 ^r4 _7 X / RNHCOO (CH ₀ ) N (CH_) _O R ⁴ - 7 ⁺ x "/ RCHOH (CH ₂ ) _n N (CH ₃ ) ₂ R - 7 X / RCH ₂ (CH ₂ ) _n N (CH ₃ ) ₂ R ⁴ - 7 ⁺ X ~

4 "

in which R, R, N and X have the same meaning as in general formula, prepared in a two-step process be by a the adamantane or another radical R containing

509835/1049

Compound is reacted with a compound containing the dimethylamine radical and the reaction product then with a higher aliphatic halide is quaternized. Another method of making the adamantyl ketones is to use a lower adamantyl haloalkyl ketone with a higher dimethylalkylamine to implement.

The following examples describe the process by which the compounds of the invention are prepared.

Example 8

Production of 2- (1'-Adamantancarboxy) -äthyldimethyldodecylammoniumbromid:

To a solution of 21.7 g (0.11 moles) of 1-adamantane carboxylic acid chloride in 100 ml of ether was a solution of 19.4 g (0.22 moles) of 2-dimethylaminoethanol given in 200 ml of ether. The reaction mixture was stirred at room temperature overnight. Because with the help of an infrared spectrum Acid chloride which had not yet reacted could be detected, a further 15 g (0.17 mol) of 2-dimethylaminoethanol were used added and the reaction mixture stirred again overnight. The reaction mixture was poured into 300 ml of water and with Treated 20 ml of a 10% NaOH solution. 23 g of an oil were obtained from the ether phase, the infrared spectrum of which was the one proposed Structure of 2-dimethylaminoethyl * -1-adamantane carboxylate corresponded.

509835/1049

Analysis: Calculated for C ₁₅ H ₃₅ NO ₂ : C = 71.67; H = 10.02.
found: C = 71.26; H = 9.94.

10 grams (0.04 moles) of the Step 1 product was mixed with 10 grams (0.04 moles) of 1-bromododecane and allowed to stand for 6 weeks. The resulting crystal mass was washed with ether and dried to give 17.5 g of white crystals (88% of the theoretical yield). Recrystallization twice from ethyl acetate gave 15.6 g of white crystals with a melting point of 176 to 178 C.

Analysis: found calculated

Carbon 64.95 64.78

Hydrogen 10.15 10.07

Example 9

4th
The decyl homologue of the above carboxylate in which R ^c -i _o ^H 21 ^ ^st 'was prepared similarly to Example 8. The crystals obtained had a melting point of 183 to 184.5 ° C and gave the following analysis result:

found calculated

Carbon 63.00 63.54

Hydrogen 9.90 9.81

Example 10

The tetradecyl homologue was made according to that described in Example 8 Process made. The crystals obtained had a melting point of 176 to 178 ° C and gave the following analysis result:

found calculated

Carbon 65.33 65.89

Hydrogen 10.18 10.30

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Example 11

Preparation of 3- (1'-Adamantancarboxamido) propyldodecyldimethylammonium bromide: 2.5 g of N, N-dimethyl-1,3-propanediamine were added to a cold solution of 5 g of 1-adamantanecarboxylic acid chloride in

■ 3
Given 15 cm of benzene. A precipitate formed immediately.

The mixture was stirred and allowed to sit for 30 minutes. The precipitate was washed several times with benzene, centrifuged and dried in vacuo. There were 5 g of M- (3-dimethylaminopropyl) adamantane-1-carboxamide hydrochloride with obtained a melting point of 154 to 157 ° C. This product was dissolved in 150 cm "acetone, and for the purpose of crystal enlargement put in a freezer. 4.8g was recovered.

3

This hydrochloride was dissolved in 100 cm of water and with 25 cm

1N NaOH added. A white precipitate formed which was extracted with ether and dried by flash evaporation. 3.2 g of the free bases with a melting point of 78 to 80 ^° C. were obtained. The infrared spectrum confirmed the structure of this product.

The reaction product described above was quaternized by adding 1f6 g (0.06 moles) of N- (3-dimethylaminopropyl) -1-adamantane carboxamide reacted with 1.5 g (0.06 moles) of 1-bromododecane dissolved in 4 cm of acetone became. After standing for 2 weeks, the reaction mixture was cooled with dry ice. The resulting crystal mass wux'de Washed with ether, dried in vacuo and recrystallized from ethyl acetate. A crystalline product resulted with a Melting point from 122 to 124 C and the following analysis result:

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found calculated

Carbon 64.81 65.47

Viassstoff. 10.84 10.40

Molecular weight: 513.66

Example 12

The tetradecyl homologue of the above carboxyamide was determined according to the Procedure prepared in Example 11. The obtained crystals had a melting point of 120 to 122 ° C and the following analysis result resulted:

found calculated

Carbon 65.80 66.52

Hydrogen 10.54 10.61

Molecular weight: 541.71

Example 13

Production of 2- (1'-adamantyloxy) ethyldimethyltetradecylammonium bromide:

A mixture of 3.6 g (0.015 moles) of 1- (2 ^I -dimethylaminoethoxy) adamantane (prepared by the method of Charkrabarti, Faulis and Szinai, Tetrahedron Letters, No. 60, 6249, 1968) and 4.3 g (0.05 moles) of 1-bromotetradecane and allowed to stand for 6 days at room temperature. The resulting precipitate

3
was recrystallized from 30 cm ethyl acetate. 4.75 g of white crystals were obtained which, after recrystallization, had a melting point of 132 to 135 ° C.

found calculated carbon 67.32 67.17 hydrogen 10.96 10.87 bromine 15.92
509835/1049 15.96

Example 14

The dodecyl homologue was obtained according to the procedure of Example 13 manufactured. Hydroscopic crystals which melted at 128 to 130 ° C. in the dry state were obtained. The analysis showed the following result:

found calculated

'Bromine 16.91 16.91

Example 15

Preparation of 1-adamantylcarbonylmethyldimethyltetradecylammonium bromide.

A mixture of 1.3 g (0.005 moles) of 1-adamantyl bromoethyl ketone and 1.23 g (0.005 moles) of dimethyltetradecylamine was obtained by adding

3
30 cm acetone brought into solution. The next day the solidified mixture was washed with ether and recrystallized from ethyl acetate. 2.1 g of white crystals with a melting point of 134 to 135.5 ° C. were obtained.

found calculated

Carbon 67.72 67.45

Hydrogen 10.65 10.51

Example 16

The dodecyl homologue was obtained according to the procedure of Example 15 manufactured. The white crystals obtained had a melting point of 140 to 141.5 ° C and gave the following analysis:

509835/1049

found calculated

Carbon 66.55 66.36

Hydrogen 9.87. 10.28

Example 17

2- (1'-Adamantylthiocarbamyloxy) ethyldimethyldodecylammonium bromide was produced in a 2 ~ step process. First, 1-adamantyl isothiocyanate was made with the sodium derivative of 2-dimethylaminoethanol implemented. After recrystallization from ethyl acetate and hexane, the reaction product had a melting point from 86 to 88.5 ° C and resulted in the following analysis:

found calculated

Carbon 64.02 63.79

Hydrogen 9.41, 9.28

A solution of 4.5 g of the 0- (2-dimethylaminoethyl) -1-adamantylthxocarbamate prepared above and 4.0 g of 1-bromododecane in 15 cm acetone was allowed to stand for 4 days. After recrystallization of the reaction product of ethyl acetate and acetone gave white crystals with a melting point of 143 to 143.5 ° C and the following analysis result:

found calculated

Carbon 61.04 60.99

Hydrogen 9.65 9.67

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Example 18

'' Production of S-decanamidopropyldimethyltetradecylammonium chloride: A solution of 102 g (1 mol) of N, N-dimethyl propylenediamine in 400 moles of benzene were admixed with 95.3 g (0.5 moles) of decanoyl chloride with simultaneous stirring and with the aid of an ice bath kept below 5O C. After the reaction mixture was allowed to stand at room temperature for one night, it became 1 liter Poured 2% sodium hydroxide solution. The benzene phase was separated off, the aqueous phase 4 times with 100 ml of ether each time extracted and the organic phases combined. The organic solution was washed with water and dried over sodium sulfate. After evaporation in vacuo, 116.5 g of oil (91% yield) remained. Infrared and NMR spectra showed that the product was N- (3-dimethylaminopropyl) decanamide.

26 g (0.1 mol) of the above amino amide were mixed with 23 g (0.1 mol) 1-chlorotetradecane and kept ^{at 100 ° C. in an oven for 70 hours.} The reaction mixture was cooled to room temperature, washed with ether and gradually recrystallized from acetone and ethyl acetate. A crystalline monohydrate with a melting point of 55 to 57 ° C to form a liquid crystal and complete liquefaction at 173 ° C resulted. When this monohydrate was dried at 75 ° C, a hydroscopic anhydrous form was obtained. This product, calculated as ₂ O * H _? O, resulted in the following analysis:

found . calculated

Carbon 69.09 68.66

Hydrogen 12.66 12.52

Nitrogen 5.59 5.52

Chlorine 6.98 6.99

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Example 19
3- (exö, cis-bicyclo / 3,3,0_7octane-2-carboxamido) propyltetradecyl-

dimethylammonium bromide

To a solution of 23 g of exo, cis-bicyclo / 3,3,0_7octane-2-carboxylic acid (Organic Sytheses 47,10) in 100 ml of benzene were given 12 ml of thionyl chloride and 1 ml of dimethylformamide. The reaction mixture was stirred for 15 minutes at room temperature. Then became the removal of HCl bubbling nitrogen through the solution for 30 minutes. The acid chloride solution was poured into a dropping funnel transferred and while stirring slowly in a solution of 34 g of N, N-dimethy! propylenediamine in 100 ml of benzene at 20 to 25 ° C given.

After 30 minutes, the reaction was terminated, the reaction mixture was poured into sodium hydroxide solution and the product with Ether extracted. A hydrochloric acid solution was added for neutralization and extracted again with ether. After evaporation of the Ether remained 31 g of a solid crystalline mass (86% of the theoretical yield). After recrystallization from Hexane melted the product at 60-63 ° C. -

Analysis: Neutral Equivalent: Calculated, 238.4; found, 241.3. A mixture of 12 g of the above compound and 14 g of 1-bromotetradecane in 100 ml of acetone was refluxed for 24 hours. On cooling, 20.4 g (78% of the theoretical yield) of crystals settled out. After recrystallization from acetone, the compound had a melting point of 119 to 122 ° C. Analysis: based on C ₂₈ H ₅₅₂

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calculated found carbon 65.21 65.05 Viassstoff 10.75 10.81 bromine 15.50 15.26 nitrogen 5.43 5.21

Example 20

3- (exo-cis-bicyclo ^ 3, 3,0_ / octane-2-carboxamido ·) propyldodecyldimethy1-

ammonium broinid

This compound was made using the same procedure as in Example manufactured and melted at 119 to 120.5 C.

Analysis: based on C ₂₆ H ₅₃

calculated found

carbon 64.04 64.01 hydrogen 10.54 10.64 bromine 16.39 16.21 nitrogen 5.75 5.57

Example 21

3- (2'-norbornane carboxamido) propyltetradecyldlmethylammonium bromide

Starting from 2-norbonanecarboxylic acid chloride, this compound was prepared by a method similar to Example 19. After recrystallization from ethyl acetate, the compound melted at 129-131 ° C.
Analysis: bromide: calculated 15.93%; found 15.61%.

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Claims (27)

Claims /I./ Chemical compound with the structural formula: Z (CH ₀ ) NR ² R ³ R ⁴ ? ⁺ X ~ in which R is an aliphatic or alycyclic group with 7 to 2 3 13 carbon atoms, R and R each is a methyl or Are ethyl radical, R ^{4 is} an aliphatic chain with 10 to 18 carbon atoms, Z is CH, O, S, C = O, COO, CONH, CHOH, NHCOO or NHCSO, η is an integer from 1 to 3 and X is a compatible Anion is. 2. Chemical compound according to claim 1, characterized in that R is an adamantyl radical and Z is COO. 3. Chemical compound according to claim 1, characterized in that R is an adamantyl group and Z is CONH. 4. Chemical compound according to claim 1, characterized in that R is a bicyclooctane group and Z is CONH. 5. Chemical compound according to claim 1, characterized in that that R is a norbornane radical and Z is CONH. 6. Chemical compound according to claim 1, characterized in that R is a decyl radical and Z is CONH. 7. Chemical compound according to claim 1, characterized in that R is a 1-adamantyl radical and Z is C = O. 509835/1049 8. Chemical compound according to claim 1, characterized in that R is a 1-adamantyl radical and Z is O. 9. 2- (1'-Adamantancarboxy) ethyldimethyldodecylammonium bromide. 10. 3- (1'-Adamantancarboxamido) propyltetradecyldimethylammonium bromide, 11. 1-Adamantane carbonylmethyldimethyldodecylammonium bromide. 12. 2- (1-Adamantyloxy) ethyldimethyltetradecylammonium bromide. 13. Process for the preparation of a chemical compound according to Claim 1, characterized in that one of the residues Compound containing R and Z with a diamine residue R and R-containing compound to a tertiary amine reacted and then quaternized with a higher aliphatic halide. 14. The method according to claim 13, characterized in that one the quaternary ammonium amides are produced by adding an aliphatic or alicyclic carboxylic acid with 7 to 13 Carbon atoms with Ν, Ν-dialkylethylene or propylenediamine to a tertiary amino amide and then quaternized with a higher alkyl halide. 509835/1049 15. The method according to claim 13, characterized in that one the quaternary ammonium esters of adamantanecarboxylic acid are prepared by reacting ademantanecarboxylic acid chloride with lower .Dialkyiaminoethanol to carboxylate and then quaternized with a higher alkyl halide. 16. The method according to claim 13, characterized in that one the quaternary ammonium ether is made by making a 1-haloadamantane reacted with lower dialkyiaminoethanol to form a tertiary amino ether and then with a higher alkyl halide quaternized. 17. Oral care mixture, characterized in that it has a compound as an effective antimicrobial agent contains the following structural formula: / RZ (Cri _o ) NR ² R ³ R ⁴ 7 ⁺ X ~, in which R is an aliphatic or alicyclic radical with 7 to 2 3
13 carbon atoms, R and R are each methyl or Ethyl radicals are R an aliphatic chain with 10 to 18 carbon atoms Z is CH ", O, S, C = O, COO, CONH, CHOH, 'NHCOO or Is NHCSO, η is an integer from 1 to 3, and X is a compatible anion. 18. Oral care mixture according to claim 17, characterized in that that it contains a non-ionic surfactant. 509835/1049 19. Mixture according to claim 17, characterized in that it contains 0.2 to 3 wt.% Of the nonionic surfactant and 0.025 to
Contains 10% by weight of the antimicrobial compound. 20. Oral care agent mixture according to claim 19, characterized in that it is an antimicrobial compound
contains quaternary aramoniuniamide. 21. Mixture according to claim 20, characterized in that it as an antimicrobial compound, a quaternary adamantylammonium amide contains. 22. Mixture according to claim 20, characterized in that it is a quaternary bicyclooctylairimonium amide as the antimicrobial compound contains. 23. Mixture according to claim 20, characterized in that it as an antimicrobial compound a quaternary morbornanammonium amide contains. 24. Mixture according to claim 20, characterized in that it is a quaternary decylammonium amide as the antimicrobial compound contains. 25. Mixture according to claim 19, characterized in that it is a quaternary ammonium adamanty! Ketone as the antimicrobial compound contains. 509835/1049 '- 33 - 26. Mixture according to claim 19, characterized in that it is a quaternary ammonium ester as the antimicrobial compound which contains adamantane carboxylic acid. 27. Mixture according to claim 19, characterized in that it is a quaternary ammonium adamantyl ether as the antimicrobial compound contains. ue: ka: bü 509835/1049