NO754425L - - Google Patents

Description

The present invention relates to new dibicyclo-[3•1•1]- and [2.2.1]-heptyl- and dibicycio-[3.1•1]- and [2.2.1]-heptenyl polyamines which are useful as antimicrobial agents, as well as algae inhibitors. They are particularly useful as hard surface disinfectants and as additives to oil drilling mud, injection salt varnishes and industrial water where bacterial control is desired.

The present invention thus relates to a new group of substituted polyamines which are useful as algae inhibitors and as broad-spectrum antimicrobial agents, particularly against gram-negative and anaerobic bacteria. The new compounds according to the invention have the structural formula:

where:

each A, which is the same or different, is substituted or unsubstituted [3.1.1]- or [2. 2.1]-bicycloheptyl or bicycloheptenyl; each n, which is the same or different, is 0 or 1; each R, which is the same or different, is alkylene of 1 to 4 carbon atoms; Z is

where

R^ is hydrogen, aminoethyl, aminopropyl, hydroxyalkyl with 1 -

4 carbon atoms, or dihydroxyaiky1 with 2-4 carbon atoms; and R 6 is hydroxyalkyl of 1-4 carbon atoms or dihydroxyalkyl of 2-4 carbon atoms; Y is either

or -F^- where

R 2 is 2-hydroxy-1,3-trimethylene, or R 1 as previously indicated;

R is hydrogen, alkyl with 1-4 carbon atoms, aminoalkyl with 2-4 carbon atoms or hydroxyalkyl with 1-4 carbon atoms, or

dihydroxyalkyl of 2 to 4 carbon atoms, i.e. 2,3-dihydroxypropyl 93 ,4-dihydroxybutyl;

R 1 is 2-hydroxy-1,3-trimethylene or R 1 as previously indicated;

and when R^ and Rg together are ethylene, R is also ethylene, and R is aminoethyl, aminopropyl or aminohydroxypropyl.

When A is [2.2.1]-bicycloheptyl or bicycloheptenyl, it has the formula:

where each R, which are the same or different, is alkyl having 1 -

4 carbon atoms or hydrogen, R', which are the same or different,

is hydrogen or alkyl with 1-4 carbon atoms, or R<*>on neighboring carbon atoms can form an olefinic bond.

In general, it is preferred that the sum of the number of carbon atoms in all the R and R' groups is 10 or less. In the most preferred compounds, R' and R are independently hydrogen or methyl, and less than 5 of all R' and R are methyl. In the most preferred embodiments, each A is either 3-3-dimethyl-norborn-2-yl or norborn-2-yl, and R 1 is ethylene.

When A is [3.1.1]-bicycloheptyl. or bicyclohepteny 1 , it has the structural formula:

where R, which are the same or different, is hydrogen or alkyl of 1-4 carbon atoms, and the dashed line indicates saturation or olefinic unsaturation, either between the c- and d- or between the d- and e-positions, the bicyclo group being attached to (R1)nover

the c, d or e position in the ring. Preferred [3•1•1]-bicyclic groups include those where R is methyl or hydrogen and no more than 4 R groups are methyl, such as 2-, 3- and 4-norpinanyl; 2-, 3- and 4-(2-norpinenyl); 2-, 3- and 4-(6,6-dimethylnorpinanyl); 2- and 4-(3,6,6-trimethyl-2-norpinenyl); 3-(2,4,6,6-tetramethyl-2-norpinenyl); 3- and 4-pinanyl; 3- and 4-(2-pinenyl); and 3- °9 4~

(3-pinenyl).

The compounds according to the invention are generally prepared according to the following reaction sequence:

where A, Z and n are as previously indicated, HX is a mono- or polybasic organic or inorganic acid, where sufficient HX is provided to protonate at least one amino group of the polyamine.

The preparation of polyamine I involves the straightforward Schiff base reaction of the appropriate ketone IV with the appropriate amine V

followed by hydrogenation of the Schiff base VI to form polyamine I.

If amine V has more than one primary amino group, it can

either be symmetrical or asymmetrical. An amine V which is a symmetrical amine', e.g. where R^ and R^ are equal when R^ and R^ are hydrogen; or where and R^ is ethylene, R^ is aminoethyl and R^ is hydrogen; or where R^ is trimethylene when-R^ is 3-aminopropyl and R^ is hydrogen; forms a single Schiff base VI. This is because regardless of which final. primary amino group of amine V reacts with ketone IV, the same product is obtained. However, when amine V is unsymmetrical, two products can be obtained. One is Schiff base VI. The other products have e.g. the formula VI(a) when

R^ and R^ are hydrogen:

or e.g., formula VI(b) when R^ is aminoethyl or aminopropyl:

where A, R-L_g and n are as stated above. Note that both products

VI(a) and VI(b) come within the scope of the definition given for Schiff base VI. When Schiff bases of formulas VI and VI(a) or VI(b) are formed, they can be separated, if desired, by the usual and well-known separation methods, e.g. distillation and the like.

As an alternative to the use of an unsymmetrical amine V

and obtain a mixture of Schiff bases VI and VI(a) or VI(b), the reaction can be carried out stepwise. For example, 1,2-diaminoethane can be transferred to a Schiff base with 1,4-di-(3,3-dimethylnorborn-2-yl)-3-pentanone, reduced catalytically, then the remaining primary amino nitrogen is selectively cyanoethylated with acrylonitrile, followed by

of catalytic hydrogenation to give 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,4,8,10-triazaoctane.

The availability and preparation of ketones VI is discussed below. Amines V are known and can be conveniently prepared. Some particularly preferred methods of preparation include condensation

tion of acrylonitrile with ammonia followed by hydrogenation to

get 3,3'-iminobispropylamine. In addition, an N-alkylated tri-methylenediamine can be reacted with epichlorohydrin, and the product formed is transferred with alcoholic ammonia to an N-alkylated-N'-(3-amino-2-hydroxypropyl)-trimethylenediamine.

In order to.mainly ill Schiff base VI, ketone IV is dissolved and

amine V in a suitable inert solvent, e.g. toluene, and is heated under reflux until the reaction is essentially complete, 5 - 20 hours being usually sufficient for water removal by azeotropic distillation. The solvent is then removed under reduced pressure, and the residue comprising Schiff base VI is dissolved in an inert solvent, preferably an alkanol,

such as ethanol or isopropanol.

After dissolution, the Schiff base VI is catalytically reduced or

chemical.

If the reduction is catalytic, any unsaturated carbon-to-carbon bonds in A will also be reduced or hydrogenated. as well as the ca rbon-til-nitrogen bond of the Schiff base VI. IN

such catalytic reductions saturate hydrogen an alkanol soln.

ning of Schiff base VI under stirring in the presence of the usual hydrogenation catalysts such as transition metals and their reducible oxides. Particularly effective catalysts are the noble metals and their oxides. A particularly preferred catalyst is platinum oxide. In general, the hydrogenation reaction is carried out in a known manner. Small particles, e.g. 100 - 300 mesh, of catalyst is mixed with the Schiff base and excess amine in alcohol and placed in a

closed system under a hydrogen gas pressure of 3 - 5 atm. After the reaction is complete, the pressure is released and the catalyst is separated from the reaction mixture by filtration. The filtrate containing the bicycloheptyl polyamine I is then further purified by usual methods. Preferably, any solvent present can be removed under reduced pressure, the residue then dissolved in diethyl ether, washed with water, followed by further washing with

saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate. the diethyl ether is removed by evaporation under reduced pressure, which gives the bicycloheptylpolyamine I usually as an oil. The bicycloheptyl polyamine can then be redissolved in lower alkanols, mixtures of lower alkanols with water, diethyl ether or dioxane and then neutralized with an acid, e.g. hydrogen chloride, or neutralized directly with aqueous acids.

Syreaddis.ion salts are then isolated, if desired, by precipitation,

evaporation or other commonly used methods.

Suitably, anions X for the salt I(a) include anions derived from inorganic acids as well as those derived from organic acids such as e.g. halide, e.g. chloride, bromide or, iodide, or sulphate, bisulphate, nitrate, phosphate, acetate, propionate, maleate, succinate, laurate, oleate, palmitate, stearate, ascorbate, gluconate, eit rat,' carbonat, bicarbonate, benzoate, salicylate, pamoate, phthalate, furoate, picolinate, dodecylbenzene sulfonate, lauryl ether sulfate, nicotinate and the like. In general, any anion derived from an acid is suitable and satisfactory when the polyamine salt anion X , e.g. chloride, must be replaced with other anions by well-known ion exchange methods.

In the production of bicyclohepteny1-polyamines, i.e. the product I where the olefinic unring in ring A is retained, a selective chemical reduction rather than a catalytic reduction is used to reduce Schiff base VI to product I.

In this chemical reduction method, the ketone IV is reacted with the appropriate amine as before, but the Schiff base VI dissolved in an inert alkanol or an ether-type solvent is reacted with a chemical reducing agent such as sodium borohydride or lithium aluminum hydride. Although as little as one equivalent of the chemical reducing agent can be used successfully, more satisfactory results are obtained if at least a 2 molar excess of, and preferably

at least a 2.5 molar excess of the chemical reducing agent is used. After the initial reaction has subsided, the reaction mixture of Schiff base VI and reducing agent can be heated under reflux for an hour or two, then cooled to room temperature and then evaporated under vacuum. The residue obtained is then further purified by treatment with mineral acid or inorganic base as described for bicycloheptyl polyamines I, and the salt can then be formed as previously described'.

The bicycloheptyl and bicycloheptenyl ketones IV are prepared by four alternative methods indicated below as (A)-(D).

(A) The condensation of acids - This method uses the following reaction scheme:

Acylative decarboxylation of acids VII is used by heating the acid to an elevated temperature either with transition metals, preferably iron, transition metal oxides. alkaline earth metal oxides, with polyphosphoric acid or with rid fluoride. Acylative reaction is most conveniently achieved by passing the acid vapors over catalysts such as heated thorium oxide airgel.

Condensation decarboxylation of an acid is the preferred method for preparing ketone IV when both groups A-(R^)n are the same, as a mixture of products is obtained when several different acids are combined in a reaction. The preferred reaction involves mixing carboxylic acid VII with reduced iron powder and stirring in an inert atmosphere at 195°-200°C for 1-6 hours to form an iron salt.

Preferably, the carboxylic acid VII and the iron are stirred in an inert atmosphere of nitrogen for at least 2 hours at 195 - 200°C.

After 2 hours, the temperature is increased appropriately to 290 - 295°C,

and stirring is continued for at least another 3 hours, 4 hours being usually sufficient. The reaction mixture is allowed to cool and then extracted with a suitable inert solvent such as diethyl ether and filtered. The solvent extracts are evaporated under reduced pressure. The remaining liquid is distilled under vacuum to isolate the ketone IV.

The carboxylic acids VII used above are prepared in various ways known per se. A particularly useful method is the addition of [2.2.1]-bicycloheptenes, e.g. camphene, isocamphodiene, P-fenchene, norbornylene or santhene, to an aliphatic acid anhydride.

In this method, a mixture of the bi-cyclic heptene and a catalytic amount, e.g. 0.2 - 0.3 mol for each mole of terpene, of a free-radical-forming catalyst such as di-t-butylperoxide, dropwise over 3 - 5 hours to a 5 - 15 molar excess of aliphatic acid anhydride boiling under reflux. After the addition is finished, the reaction mixture is heated under reflux for 5 - 10 hours, evaporated under reduced pressure and the liquid residue is mixed with aqueous sodium hydroxide and stirred while heating on a steam bath for approx. 2 - 5 hours. The cooled alkaline solution is then extracted with ether, the ether layer is discarded, and the aqueous solution is acidified and then extracted well with ether. The combined ether extracts are washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The remaining liquid or solid is distilled under vacuum, whereby the corresponding carboxylic acid -VII is obtained.

Other carboxylic acids are easily obtained, e.g. by the Diels-Alder reaction of cyclopentadiene and alkyl-substituted cyclopentadiene with various unsaturated carboxylic acids, which will be explained below.

Another useful general method for this synthesis of the bicyclo-[2.2.1]-heptyl-substituted-alkanoic acid compounds utilizes the free-radical catalyzed addition of methyl- or ethyl-alkanoate to unsaturated bicyclo-'[2.2.2]-heptenes. The free-radical catalysis is obtained with e.g. di-t-butyl peroxide which predominantly abstracts a carbonyl-adjacent hydrogen from the alkyl alkanoate

[D. J. Trecker and R.S. Foote, J. Org. Chem. , 33., 3527-34 (1968)]. Addition of the formed free radical to the olefinic terpene gives the corresponding esters. Common hydrolysis methods, e.g. dilute aqueous sodium hydroxide, leads to alcohol liberation.e .

(B) Condensation of a Grignard reagent and a nitrile Disubstituted bicycloheptyl or bicycloheptenyl alkanones can also be obtained according to the following reaction scheme:

where (R-^)^ in the reactants may be the same or different.

In the preparation of di-(substituted bicycloheptyl)-alkanols, a general method utilizes the reaction of a Grignård reagent prepared from a chlorine- or bromine-substituted alkyl bi-cyclo-[2.2.1]-heptane with a cyano-substituted alkyl bicyclo-[2 .2.1 ]-heptane. The formed disubstituted iminoalkane salt complex is hydrolyzed with mineral acid to the corresponding ketone.

The Grignard reagent is obtained by reacting the halide with magnesium meta 11, usually in the form of shavings or powders, and catalyzed with very small concentrations of iodine or methyl iodide. Solvents that are useful include diethyl ether, dibutyl ether, tetrahydrofuran, dioxane and benzene. Usually, gentle heating is sufficient to initiate the reaction, and the halide is gradually added to the meta solvent mixture. After the addition has ended, the disappearance of practically all magnesium metal indicates that the reaction has ended. A small excess of metal is used, and moisture must be excluded, and a nitrogen atmosphere is favorable. The nitrile in two to three times its volume of . solvent is then added to the Grignard reagent over 15 minutes to 1 hour at room temperature. The reaction mixture can be heated to reflux to ensure complete conversion.

In general, a small excess of Grignard reagent is used in relation to the nitrile. From 1 to 10 hours of refluxing is sufficient for complete transfer. The formed imine salt is preferably split into the ketone with aqueous mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid. The ketones are water-insoluble and can be extracted with water-miscible solvents. Purification is preferably carried out by fractional distillation under reduced pressure. It is practically feasible to use it raw. ketone-re.k's ionic mixture for the alkylation of polyamines as the reaction by-products are usually alcohols or hydrocarbons and do not react with amines. The halide reactant, if present in the crude product, should be removed prior to the ketone-amine alkylation process.

The concentrations of Grignard reagent and nitrile can be varied

within wide limits to ensure good yields with the method.

The halide and cyano-, as well as carboxylic acid derivatives of bicycloheptanes and bicycloheptenes are commonly available and have been obtained from such bicycloheptanes and bicycloheptenes as norcamphane, apocaraphane, camphane, α-fenchan, santan, camfenilan, α-fenchan, isocamphan, (3-fenchan . , pinane, a-pinene and (3-pinene.

When these carboxyl, cyano or halogen derivatives are not readily available, they can be prepared by known methods, e.g. The Diels-Alder condensation as described in US Patent 3-595-917 and "Newer Methods of Preparative Organic Chemistry", K. Alder Inter-science,' New York, New York, 1948, pages 381-456, f.<e >

where D is R, -(R^^COOH, -(R]L)n-X or -(R1)n~CN, and where R± , R and X are as indicated above. When D is R and each R is alkyl , the bicycloheptene obtained can be reacted with an aliphatic acid anhydride as previously described.

(C) Reaction of acid halides and rnanolic acid esters The third alternative method of preparation

ketones IV use the reaction scheme:

where A, R • and n are as indicated above, and R<*>is the alkylene with 1 -

3 carbon atoms.

The bicyclo-[2.2.1]-heptyl-substituted malonic acid esters are prepared e.g. either from cyclopentadienes and alkenyl-substituted malonic acid esters followed by catalytic hydrogenation of the formed heptene derivatives to heptanes, or by alkylation of malonic acid esters with a halogen-substituted 'bicyclo-[2.2.1]-heptane, where the halogen is preferably chlorine or bromine bound directly to the ring as part of an alkyl substituent.

The sodium derivative IX of t-butylmalonic acid ester is prepared by adding a small molar excess of sodium hydride to a solution of the rmalonic acid ester VIII in an inert solvent such as anhydrous benzene. The reaction is carried out by heating, suitably to 60 - 80°C, with stirring until the hydrogen gasiit winding ceases, the reaction system being protected from atmospheric moisture. A solution of an equimolar amount of acid halide X using sufficient anhydrous benzene to just dissolve the acid halide is added and the reaction mixture is heated under reflux for about 5-20 minutes. The mixture is cooled, and any excess of sodium hydride is destroyed by adding anhydrous p-toluenesulfonsy tb. The reactive ion mixture is clarified by filtration, and the solvent is driven off under reduced pressure. The residue is dissolved in glacial acetic acid containing 0.3 - 0.5% by weight of anhydrous p-toluenesulfonic acid and approx. 2 volume% acetic anhydride. The solution is dissolved and heated under reflux for approx. 1 hour and then cool to room temperature. The solution is poured over ice, neutralized with aqueous sodium hydroxide, and the crude product of ketone IV is extracted with diethyl ether. The ether solution is washed with water, dried over anhydrous magnesium sulfate, filtered, and the solvent is evaporated.

(D) Condensation of a ketone with a ketone or aldehyde<p>g followed by reduction

A fourth method for preparing ketone IV involves the condensation of a ketone and a ketone or aldehyde according to the following reaction principle:

where A, which are the same or different, R 1 , R 1 and n are as above, and R 1 , which are the same or different, are methyl, ethyl or hydrogen.

The reaction comprises mixing the ketone XIV with a molar equivalent or small excess of aldehyde or ketone XV under stirring and cooling in the presence of catalytic amounts of sodium methylate. The reaction mixture is then kept at 40 - 55°C for approx. 4 - 10 hours and then cooled to room temperature. The reaction mixture is made acidic and after driving off the solvent under reduced pressure, the residue is extracted with diethyl ether. The ether extracts are washed with water and dried over magnesium sulfate. The solvent is then driven off under reduced pressure.

The residue XVI is dissolved in thiophene-free benzene and shaken under a pressure of 3 - 5 atm hydrogen in the presence of a noble metal catalyst on carbon at 20 - 30°C. The catalyst is then removed by filtration, and the solvent is removed. The residue is IV which can be further purified by usual methods.

Once the ketone IV is obtained, it can then be reacted with a suitable polyamine V. Polyamines V which are particularly suitable for reaction with ketone IV include diethylenetriamine, triethylenetetramine, 3,3'-imino-bis-(propylamine), 3,3' -methylimino-bis-(propylamine) , dipropylenetriamine, N,N'-bis-(3-aminopropyl)-1,3-trimethylenediamiri, N,N *-bis -(2-aminoethyl)-1,3-trimethylenediamine, N ,N'-bis-(3-aminopropyl)-piperazine, N-(2-aminoethyl)-1,3-trimethylenediamine, spermidine, spermine, 1,4-bis-(2-aminoethyl)-piperazine, tris-(2 -aminoethyl)-amine, 1-(2-aminoethyl)-4-(3-aminopropyl)-piperazine, 1-(3-amino-2-hydroxypropyl)-4-(2-aminoethyl)-piperazine, N-(3 -amino-2-hydroxypropyl)-1,3-trimethylenediamine, 1-(2,3-dihydroxy-propyl)-1,5,9-tria zanonan, 1-(2-hydroxyethyl)-1,4,7, 10-t et raaza-decan., 4 - (3 ,4-dihydroxybutyl)-1 ,4 , 8-t riazaoct an , 1-(2-hydroxy - propyl)-5-hydroxymethy1-1,5,9-triazanonan and tris-(3-aminopropyl)-amine, ethylenediamine, trimethylenediamine and 1,3-diamino-2-hydroxy-propane.

Suitable bicycloheptanes obtained by several synthetic routes described herein can be in exo- and endo-isomer configurations, and are generally a mixture of both. Many factors enter into the actual ratio of the isomers formed, and these may be temperature, solvents, steric effects, equilibrium conditions, the nature of substituents and others. However, it seems that the applicability of the products according to the invention is fulfilled without . the necessity for strict regulation of the isomer composition. The content of a product mixture can be determined by vapor or liquid phase chromatography, NMR spectral analysis, fractional distillation and other methods. It is also possible to isolate pure isomers by choosing these and other known separation methods.

The following examples will further illustrate the invention.

Example A

Preparation of 5-norbornene-2-butyric acid

A solution of 120 g (1 mol) 5-vinyl-2-norbornene and 0.1 mol (14.6 g) di -t-butyl-perpxyd. After completion of the addition, the mixture is heated under reflux for 5 hours. The cooled reaction mixture is evaporated under reduced pressure, whereby a yellow-orange residual oil is obtained, to which 750 ml of 2.5 N sodium hydroxide is added, and the reaction mixture is then heated on a steam bath for 1 hour. The cooled solution is extracted once with ether, acidified with concentrated hydrochloric acid, and carefully extracted with ether. The ether extracts are dried with sodium sulfate, evaporated under reduced pressure, and the residue is distilled under vacuum whereby 35.5 g (20%) of a colorless product with a boiling point of 120 - 124°C/0.2 mm is obtained.

Similarly, 3-(2-norbornene-5-y1)-propionic acid is produced from 5-ethylidene-2-norbornene; 1,5,5-trimethylnorborn-3-ylacetic acid from £-fenchen; 5,5-dimethyl norborn-2- and 3-yl-acetic acid from camphenylene; 2 , 5 , 5-trimethylnorborn-3-yl-acetic acid from

y-fenchen; 3-(7,7-dimethylnorborn-2-yl)-propionic acid from α-fenchen; 3-(3,3-dimethylnorborn-2-yl)-propionic acid from camphene; 3-(norborn-2-yl)-propionic acid from norcamphen; norborn-2-isoacetic acid from norbornylene; 7,7-dimethylnorborn-2-yttoacetic acid from apobornylene; 1,7,7-trimethylnorborn-3-acetic acid from bornylene; 2,3-dimethylnorborn-2-yl-acetic acid from santen; 3-(5,5-dimethylnorborn-2-en-6-yl)-propionic acid from isocamphodiene; 3-(2,2-dimethylnorborn-5-yl)-propionic acid from (3-fenchene; 2 , 7 , 7-trimethylnorborn-3-ytacetic acid from £-fenchene; 1,2 , 3-triime hy lnorbor n- 3-y 1-acetic acid from £-fenchen and 1,2,3,4,5,5,6,6,7,7-decamethyl-bicyclo-[2.2.1]-heptan-3-yl-acetic acid from 1,2,3,4,5,5,6,6,7,7-decamethyl-bicyclo-[2.2.1]-hept-2-ene obtained by Diels-Alder condensation of 1,1,2,3 ,4,5-hexa-methylcyclopentadiene and 1,1,2,2-tetramethylethylene.

Example B

Bicyclo-[2.2.1]-heptyl-substituted alkanoic acids

A solution of 15 mol of an alkyl alkanoate ester, 14.1 g (0.14 mol) of norbornene and 3.3 g (2.25 x 10~ mol) of di-t-butyl peroxide is placed in a 3 liter stainless steel autoclave. The autoclave is flushed with nitrogen and then rocked at 140°C for 12 hours. After cooling, unreacted norbornene, ester and peroxide cleavage products are driven off from the autoclave contents. The remaining liquid, which constitutes the reaction product, is purified by fractional distillation.

Ethyl acetate and norbornene give ethyl norborn-2-yl acetate,

kp. 62°C/8.5 mm in 64% yield and methyl isbbutyrate and norbornene give methyl-2-methyl-2-(norborn-2-yl)propionate, b.p. 849C/l.2 mm in 55% yield. These esters are then hydrolysed in aqueous hydrochloric acid, whereby (norborn-2-yl)-acetic acid and 2-methyl-3-(norborn-2-yl)-propionic acid are obtained.

Example C

Production of 1 . 3-di3-dimethylnorborn-2-yl)-2-propanone

36.4 g (0.20 mol) of 3,3-dimethylnorborn-2-yl-acetic acid and 0.1 g (0.11 mol) of hydrogen-reduced iron are heated for 1.5 hours at 195° C. under a nitrogen atmosphere. The temperature is then increased to

290°C, and this temperature is maintained for 3 hours. The cooled reaction mass is extracted well with ether, filtered through "Celite", and the ethereal extracts are evaporated under vacuum. The remaining reddish oil is distilled under vacuum leaving the product as a pale yellow liquid, 21.59(71%), b.p. 156 - 159°C/Q,1 mm..

Analogously, 1,3-di-(nor-born-2-yl)-propanone is prepared in a similar way from 2-norbornane-acetic acid; 1,7-di-(5-norbornen-2-yl)-4-heptanone from 4-(5-norbornen-2-yl)-butyric acid; 2,6-di-(5-norbornen-2-yl)-4-heptanone from 3-(5-norborn-2-yl)-butyric acid; 1,3-bis-(1,5,5-trimethylnorborn-3-yl)-propanone from 1,5,5-trimethyl-norborn-3-yl-acetic acid; 1,3-bis-(5,5-dimethylnorborn-2- and 3-yl)-propanone from 5,5-dimethylnorborn-2- and 3-yl-acetic acids; -1, 3-bis-(2,5,5-trimethylnorborn-3-yl)-propanone from 2,5,5-t rimethy 1 - . norborn-3-yl-acetic acid; 1,5-bis-(7,7-dimethylnorborn-2-yl)-pentan-3-one from 3-(7,7-dimethylnorborn-2-yl)-propionic acid; 1,5-bis-(3,3-dimethylnorborn-2-yl)-pentan-3-one from 3-(3,3-dimethylnorborn-2-yl)-propionic acid; 1,5-bis-(norborn-2-yl)-pentan-3-one from 3-(norborn-2-yl)-propionic acid:, 1,3-bis-(norborn-2-yl)-propanone f ra norborn-2-yl-acetic acid; 1,3-bis-(7,7-dimethylnorborn-2-yl)-propanone from 7,7-dimethylnorborn-2-yl-acetic acid; 1,3-bis-(1,7,7-trimethylnorborn-2-yl)-propanone from 1,7,7-trimethylnorborn-2-yl-acetic acid; 1,3-bis-(2,3-dimethylnorborn-2-yl)-propanone from 2,3-dimethylnorborn-2-yl-acetic acid; 1,5-bis-(5,5-dimethylnor-born-2-en-6-yl)-pentan-3-one from 3-(5,5-dimethylnorborn-2-en-6-yl)-propionic acid; 1,5-bis-(2,2-dimethylnorborn-5-yl)-pentan-3-one from 3-(2,2-dimethylnorborn-5-yl)-propionic acid; 1,3-bis-(2,7,7-trimethylnorborn-3-yl)-propanone from 2,7,7-trimethylnorborn-3-yl-acetic acid; 1,3-bis-(1,2,3-trimethylnorborn-3-yl)-propanone from 1,2,3-trimethylnorborn-3-yl-acetic acid;. 1,3-bis-[1,2,4,5,6,7-hexamethyl-7-propyl-[2.2.1]-hept-5-en-3-yl]-acetone from 1,2,4, 5,6,7-hexamethyl-7-propyl-[2.2.1]-hept-5-en-3-y1-acetic acid which is prepared by Diels-Alder condensation of 1-methyl-1-propyl-2,3, 4,5-tetramethylcyclopentadiene and•4-methylvinylacetic acid; bis-[1,2,2,3,4,5,6,7,7-nonamethy1-bicyclo-[2.2.1]-hept-5-en-3-yl]-acetone from 1,2,2, 3,4,5,6,7,7-nonamethyl-bicyclo-[2.2.1]-hept-5-en-3-yl-acetic acid which is prepared by Diels-Alder condensation of 1,1,2 , 3 ,4,5-hexamethylcyclopentadiene and 3,4,4-trimethyl-vinyl-acetic acid; 1 , 3 -di - (2 ,4 , 6 , 6-t ramethy 1-2-norpinen-3-yl)-2-propanone from 2,4,6,6-tetramethyl-1-2-norpinen-

3-yl-acetic acid; 1,3-di-(2-pinen-4-yl)-2-propanone from 2-pinen-4-yl-acetic acid; 1,5-bis-(6,6-dimethylnorpinan-4-yl)-pentan-3-one from 3-(6,6-dimethylnorpinan-4-yl)-propionic acid and 1,5-bis-(norpinan-2 -yl)-pentan-3-one from 3-(norpinan-2-yl)-propionic acid.

Example D

Preparation of 2-(bicyclo-[ 2.2.1 ]-hept-an-2-y 1 -acetyl)-bicyclo-[ 2.2.1]-heptane

The sodium derivative of di-t-buty1-bicycio-[2.2.1]-heptan-2-yl-malonate is prepared by adding 0.36 g of sodium hydride to a solution of 3,19-malonic acid ester in 75 ml of anhydrous benzene. An "Asearite" drying tube (sodium hydroxide asbestos preparation) is connected to the return cooler. The reaction is carried out by heating at 80°C with stirring until the evolution of hydrogen gas • ceases (approx. 2.5 hours). A solution of 16 g of bicyclo-[2.2.1]-heptan-2-yl-carboxylic acid chloride in 30 ml of anhydrous benzene is then added, and the reaction is carried out under reflux for approx. 10 minutes. The mixture is cooled to room temperature, and excess sodium hydride is destroyed by adding 0.99 anhydrous p-

f

toluenesulfonic acid. The mixture is clarified by filtration, and the solvent is driven off from the filtrate under reduced pressure. The residue is dissolved in 75 ml of glacial acetic acid containing 0.3 g of anhydrous p-toluenesulfonic acid and 2% by volume of acetic anhydride. The solution is heated under reflux for 1 hour, cooled to room temperature, poured over crushed ice, neutralized by adding 5% sodium hydroxide solution, and the product is extracted with diethyl ether. Ether solutions are washed with water, dried over anhydrous magnesium sulfate, filtered, and the solvent is evaporated. The residue is essentially pure 2-(bicyclo-[2.2.1]-heptan-2-yl-acetyl)-bicyclo-[2.2.1]-heptane.

Under the same reaction conditions, the following ketones are obtained: 1-[3-methylbicyclo-[2.2.1]-hept-2-yl]-6-[3,3-dimethyl-bicyclo-[2.2.1]-hept-2 -yl]-hexan-3-one from 3-methylIbicyclo-[2.2.1]-hept-2-yl-methylmalonic acid ester and 4-[3-,3-dimeth<y>Ibic<y>clo-[2.2.1 ]-hept-2-yl]-butyryl chloride, and 1 -[ 5 ,6-diethylbicyclo-[2 .2 .1 ]-he*pt - 2-yl]-4-[1,7,7-trimethylIbicyclo-[ 2.2.1]-hept-2-yl]-butan-2-one from 5,6-diethylbicyclo-[2.2.1]-hept-2-yl-acetyl chloride and 1,7,7-trimethylbicyclo-[2.2.l ]-hept-2-yl-methylmalonic acid ester.

Example E

Preparation of 1 -(1,7,7~trimethyIbicyclo-[2.2.1]-hept-2-yl)-4~

(1,3,3-trimethyIb icyclo-[ 2.2.1]-hept-2-yl)-butan-2-one

20.6 g (0.1 mol) of 1-(1,3,3-trimethylbicyclo-[2.2.1]-hept-2-yl)-1-buten-3-one and 18.3 .9 (0, 12 mol) of camphor are dissolved in 25 ml of methyl alcohol. A solution of 3.49 potassium hydroxide in 20 ml of methyl alcohol is then added over the course of 15 minutes with good stirring and external cooling. The reaction mixture is kept at 40 - 45°C for 6 hours, cooled to 20°C, made slightly acidic by the addition of dilute hydrochloric acid, and the residue, after stripping off the solvent under reduced pressure, is extracted with ether. The ether solution is washed twice with 1/10 of its volume with cold water, dried over anhydrous magnesium sulfate, and the solvent is driven off under reduced pressure. The remaining oil containing 1-(1,7,7-trimethyIbicyclo-[2.2.1]-hept-2-ylidene)-4~(1,3,3-trimethyIbicyclo-[2.2.1]-hept -2-y1)-but-3-en-2-one, dissolves in

100 ml of thiophene-free benzene and shaken under 3.5 kg/cm hydrogen pressure in the presence of 395% palladium-on-carbon at 25°C until slightly more than the theoretical amount of hydrogen is taken up. The catalyst is removed by filtration, and the solvent is driven off.

The remaining oil is purified by fractional distillation under reduced pressure, whereby 1-(1,7,7~trimethylbicyclo-[2.2.1]-hept-2-yl)-4-(1,3,3-trimethylbicyclo-[2.2 .1]-hept-2-yl)-butan-2-one.

In the same synthetic methods, the use of other aldehyde and ketone-bicyclo-[2.2.1]-heptane derivatives gives the following di-alicyclic alkanones:

Example F

Preparation of 2-[1,7,7-trimethylIbicyclo-[2.2.1]-hept-2-yl-acetyl]-bicyclo-[2.2.1]-heptane

(a) Preparation of the Grignard reagent of (bicyclo-[2.2.1]-hept - 2- yl - bromide)

The reagent is prepared in a dry apparatus under nitrogen by adding 5.0 g (0.02.9 mol) of the bromide in 20 ml of dry ether to 1.0 g (0.04 l g atom) of magnesium under 15 ml of ether containing a crystal of iodine. The mixture is boiled under reflux for 1 hour. This Grignard reagent can also be prepared by the method of H. Kwart and L. Kaplan, J. Am. Chem. Soc, 76, 1072 (1954)-(b) Reaction of the Grignard reagent with 1,7,7-trimethyl-bicyclo-[2..2.1]-hept-2-yl-acetonitrile

A solution of 3.5 g (0.02 mol) of 2-bornane-acetonitrile i

15 ml of anhydrous ether are added over 15 minutes to the well-stirred Grignard reagent from (a) above. After the addition is complete, the reaction mixture is stirred for a total of 12 hours. It is then poured onto a mixture of 50 g of ice and 20 ml of concentrated hydrochloric acid. The ether is removed under reduced pressure, and the remaining mixture is heated under reflux for 1 hour. The cooled mixture is extracted with 2 x 50 ml of ether, the organic layer is separated, washed with cold water, dried over anhydrous magnesium sulfate, filtered, and the solvent is removed by distillation. The residue is subjected to fractional vacuum distillation whereby 2-[1,7,7-trimethylIbicyclo-[2.2.1]-hept-2-yl-acetyl]-bicyclo-

[2.2.1]-heptane in its pure state, typically IR-carbonyl absorption at 5.8 (im) is used to characterize the product.

Under the same conditions, but by using the following halides instead of norbornyl bromide and reacting the corresponding Grignard reagent with 1,7,7-trimethylbicyclo-[2.2.1]-heptan-2-yl-acetonitrile, the following ketone intermediates are obtained :

Additional examples of compounds prepared according to this method include:

Example 1

Preparation of 1-[1 , 5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1 , 5 , 9 - triaza nona n-trihydrochlor id

6.04 g (0.02 mol) 1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentanone and 13.19 (0.10 mol) 3,3'-imino-bis- propylamine in 150 mL toluene is heated under reflux overnight with a Dean-Stark water separator. The cooled solution is evaporated under reduced pressure. The residue is dissolved in ethanol and hydrogenated with platinum oxide at room temperature and 2.8 kg/cm hydrogen pressure. The plate in the alysator is filtered, and the ethanol is removed under vacuum. The remaining oil is dissolved in ether, and the ether solution is washed several times with water to remove excess 3,3'-imino-bis-propylamine. The ether extracts are dried over anhydrous sodium sulfate and evaporated under vacuum which gives the polyamine as a colorless oil (8.3 g, 100% yield).

The oil is dissolved in ether, and hydrogen chloride gas is bubbled into the solution until no further precipitation occurs. The ether is evaporated under reduced pressure, leaving the product as a solid which is dissolved in hot isopropyl alcohol. The solid is collected by filtration and dried under vacuum at 70°C, which gives 10.89 (97%) of a colorless product with a melting point of 26o - 262°C.

In an analogous way with regard to quantities and reaction conditions, and using 1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentanone and the amines indicated above, the following process compounds are prepared:

Furthermore, in an analogous manner with regard to quantities and reaction conditions, but by using 1,<3>-di-(3,3-dimethylnorborn-2-yl)-2-propanone and respectively 3,3'-imino-bis-propylamine and triethylenetetramine, the hydrochlorides of 1-[1,3-di-(3,3-dimethylnorborn-2-yl)-2-propyl]-1,5,9-triazanonane and 1 -[1,3-di-(3,3-dimethylnorborn-2-yl)-2-propyl]-1,4,7,10-tet crude azadecane.

Example 2

Preparation of 1-[1,5-di-(2-norbornyl)-3-pentyl]-1,5,9-triaza-nona n- t r y d r o k i o r i d

4.15 g (0.015 mol) of 1,5-di-(2-norbornyl)-3-pentanone and

9.8 g (0.075 mol) of 3,3'-imino-bis-propylamine 150 ml of ethanol are heated under reflux for 3 hours. The cooled solution is hydrogenated with platinum oxide at room temperature and 2.8 kg/cm hydrogen pressure. The platinum catalyst is filtered off and the ethanol is removed

under vacuum. The remaining oil is dissolved in ether, and the ether solution is washed several times with water. The ether extracts are dried over anhydrous sodium sulfate and evaporated under vacuum to give the polyamine as an oil, 5.89 (99%).

The oil is dissolved in absolute methanol and cooled in an ice-water bath. Hydrochloride gas is bubbled into the solution. The methanol is evaporated under reduced pressure which gives a gummy solid which is crystallized from isopropyl alcohol which gives 6.0 g (80%) product as colorless crystals with a melting point of 257 - 258°C.

In this method, 1-[1,3-di-(2-norbornyl)-2-propyl]-1,5,9-triazanonane trihydrochloride is also prepared in an analogous manner with regard to molar amounts and reaction conditions from 1,3- you -

(2-norbornyl)-2-propanone and 3,'3'-imino-bis-propylamine; l-[l,3~di-2-norbornyl-2-propyl]-1,4,7,10-t et raazadecan-t et r ah yd r oki or id from 1,3-di-(2-norbornyl )-2-propanone and triethylenetetramine; 1-[1,7-di-(2-norbornyl)-4-heptyl]-1,5,9-triazanonan trihydrochloride from 1,7-di-(2-norbornyl)-4-heptanone and 3, 3'-imino-bis-propylamine;

and 1-[2,6-di-(2-norbornyl)-4-heptyl]-1,5,9-triazanonan-trihydric chloride from 2,6-di-(2-norbornyl)-4- heptanone and 3,3'-imino-bis-propylamine..

Example 3

Preparation of 1-[1,7-di-(5-norbornen-2-yl)-4-heptyl]-1,5,9-tri-azanonan-trihydrochloride

5.96 g (0.02 mol) 1,7-di-(5-norbornen-2-yl)-4-heptanone and 13.1 g (0.10 mol) 3,3'-imino-bis-propylamine in 150 ml of toluene is heated under reflux overnight with a Dean-Stark water separator. The toluene is then removed under vacuum. The remaining oil dissolved in 25 ml of isopropanol is added dropwise to 1.90 g

(0.05 mol } excess) of sodium borohydride suspended in 50 ml of isopropanol. After the addition is finished, the reaction mixture is heated under reflux for 1 hour. The isopropanol is evaporated under reduced pressure, the residue is treated with water, and the aqueous mixture is extracted well with ether. The combined ether extracts are backwashed with water, a saturated sodium chloride solution, dried over anhydrous sodium sulfate and evaporated under vacuum whereby 7.4 g (90%) of the amine product is obtained as a clear oil.

The oil is dissolved in ether, and the solution is cooled in an ice-water bath. Hydrogen chloride gas is bubbled into the solution until no further precipitate forms. The solid is collected by filtration, washed with a small amount of ether and dried under vacuum, whereby the amine trihydrochloride is obtained as a colorless product (96%).

Example 4

Preparation of 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1, 4, 8- t r ia za oet an ■

A mixture of 9.9 g (0.03 mol) 1,5-di-(3,3-dimethyl-norborn-2-yl)-3-pentanone and 12.0 g (0.20 mol) 1,2 -diaminoethane i

250 ml of ethanol is heated under reflux overnight. The cooled reaction mixture is hydrogenated with platinum oxide at room temperature and 2.8 kg/cm 2 hydrogen pressure. The platinum catalyst is filtered off, and the ethanol is removed under reduced pressure. The remaining oil is dissolved in ether, and the ether solution is washed several times with water to remove excess diaminoethane. The ether extracts are dried over anhydrous sodium sulfate and evaporated under vacuum, which gives 11.2 g (100%) of a colorless oil.

The oil is dissolved in 20 ml of t-butanol and cooled to 0 - 5°C i

an ice-water bath. 1.75 g (2.2 ml, 0.033 mol.) of acrylonitrile is added dropwise over 5 minutes. The reaction mixture is allowed to warm to room temperature and then heated at 60°C overnight. The t-butanol is removed under reduced pressure. The remaining oil is dissolved in 150 ml of glacial acetic acid and hydrogenated with platinum oxide at room temperature and 2.8 kg/cm<2> hydrogen pressure. The platinum catalyst is filtered off, and the acetic acid is removed under vacuum.

The residue is dissolved in ether and made alkaline with 10% sodium hydroxide. The ether solution is washed with water, dried over water

free sodium sulfate and evaporated under reduced pressure which gives 12.5 g of a pale yellow oil. The oil is chromatographed on active

tet III Woelm aluminum oxide Elution with 20% methanol/chloroform gives 4.35 g (33%) of an analytically pure product.

Thin layer chromatography on silica gel G and development with ethanol/ammonium hydroxide (4:1) shows a spot R^. 0.45.

Moreover, the compounds according to the invention were indicated in

the table below prepared by the reactions indicated in the preceding examples. It should be noted, however, that the [3.1.1]-bicycloheptenes are prone to rearrangement when attempts are made to introduce substituents by free-radical mechanisms as in example A. Therefore, it is preferred that [3•1•1]-bicyclic heptylcarboxylic acids are prepared by other known methods.

Moreover, each of the respective ketones IV set forth in Examples C, D, E, and F, when reacted with each of the individual amines set forth in this specification, first according to the procedure set forth in Example 1, and then according to to example 3, the entire range of compounds covered by formula I.

The polyamines described here are excellent broad-spectrum antimicrobial agents which are particularly effective against gram-positive and gram-negative bacteria, especially the troublesome gram-negative bacteria of the genus Pseudomonas at aqueous concentrations of 1.0 to 100 ppm; Examples of sensitive species include e.g. Staphylococcus aureus, Streptococcus pyogenes, Bordetella bronchiseptica, Pasteurelle multocida, Escherichia coli, Sal-monella typhimurium, S. pullorum, Klebsiella pneumoniae, Aero-bacter aerogenes, Pseudomonas aeruginosa, Desulfovibrio desulfuricans, Bacillus mycoides, fungi such as Aspergillus niger and Chaetomium globosum. When used, these compounds can be applied in pure form or used in a diluted form. Satisfactory diluents include any inert material which is not destructive to the antimicrobial activity and in particular liquid preparations comprising aqueous dispersions, solutions and emulsions. Solid diluents include talc, corn starch, aluminum oxide and diatomaceous earth. The antimicrobial agents according to the invention can also be applied to materials such as natural fibers including paper, cotton, wool and synthetic fibers such as nylon and polypropylene, as well as to inanimate surfaces including hard surfaces such as wood, glass, metal, ceramic tiles, rubber and plastic. and porous surfaces such as concrete, leather and the like.

The polyamines produced according to the invention are particularly useful for suppressing the growth of aerobic and anaerobic bacteria in fluids used in cutting and grinding operations, such as metalworking, and oil well drilling mud or secondary oil recovery fluids and brines. Anaerobic microorganisms such as the sulphate reducer, Desulfovibrio desulfuricans, are inhibited at 0.1 - 10 ppm concentration of these polyamines. Suppression of these bacteria eliminates hydrogen sulphide formation and corrosion on equipment, plugging of oil-bearing sand, unpleasant odors and other harmful effects. These compounds are also useful for the preservation against biodegradation of other aqueous systems such as aqueous emulsions and dispersions, paints and coatings, pigment suspensions, adhesives, etc., where rapid reproduction of microorganisms can cause colloid degradation, pH changes, unpleasant odors, corrosive substances, viscosity -losses and other undesirable effects.

A particularly useful application of the process compounds is to impart sanitizing properties to textiles, both woven and non-woven, washable or disposable, to be used e.g. such as nappies, surgical masks, hats, gowns, towels and curtains, covers for hospital furniture and instrument wrappings, aseptic cleaning paper and sanitary napkins and toilet paper. In this application, the compounds of formula I may be applied to the fibrous pulp prior to tissue forming or threading, or they may be sprayed onto the finished product. Both application methods are satisfactory as long as from 1 x 10^% by weight or more of the antimicrobial material is retained on the fabric. More than 0.1 -

1% by weight is generally too much and redundant.

Another use is alone or in solution or suspension or in conjunction with soaps or detergents for

use in cleaning the skin, especially in pre-surgical scrubbing preparations, or in preparations for combating the growth

of Corynebacterium acnes. C. acnes is a bacterial strain implicated in acne conditions, especially Acne vulgaris, where applications of as little as 1-5 ppm are effective in combating such bacteria that live in the skin. Larger concentrations can be used if desired without irritation or discomfort such as 2500 ppm and higher. When the cleaning preparation is diluted with water during use, the preparation can contain from 0.01% by weight and more of the polyamine produced according to the invention.

Moreover, the process compounds can be used in retained water, such as swimming pools, ponds and water used in industry as waste water in paper mills, to inhibit the growth of unwanted bacteria, fungi and/or algae in amounts as low as 0.5 - 5 ppm.

To combat slime-forming microorganisms and algae in recirculating industrial water, particularly in cooling operations and special installations such as cooling towers, the polyamine compounds produced according to the invention are generally used alone, but they can also be used in combination with other antimicrobial agents. The compounds are preferably used as salts to increase solubility. Concentrations in recirculating water of as little as 1 x 10% by weight are effective in inhibiting microbe growth. To ensure effectiveness, especially against more resistant strains of microorganisms, and also when additional water is added to replace water lost through evaporation and the like,

-U-2

concentrations from 1 x 10 to 5 x 10% by weight are particularly satisfactory. The dosage can be continuous or intermittent "shock treatment", i.e. addition for a 10 - 20 minute period every 4 - 8 hours.

An unusual, very advantageous property of the process compounds is high coverage on all kinds of surfaces. This provides protection against corrosion and acts as a storage depot for continuous dosing of the waters in contact with them. The same properties are also mainly responsible for the previously indicated use as disinfectants for inanimate surfaces including walls and ceilings, equipment, animal stalls, hospital rooms, kitchens and bathrooms and the like.

When working up the process compounds for the above applications, the compounds can be used in combination with other antimicrobial agents, surfactants, insecticides, anti-foaming agents, deodorants or as chelates of metals such as copper, calcium, magnesium and iron.

Claims (27)

1. Antibacterial compound, characterized in that it has the formula: where each A is the same or different, and is a [2.2.1]-bicyclic group with the formula:a) or a [3.1.1]-bicyclic group of the formula:b) where R, which is the same or different, is hydrogen or alkyl with 1-4 carbon atoms, R <*> , which is the same or different, is hydrogen or alkyl with 1-4 carbon atoms or R <*> on neighboring carbon atoms can together form an olefinic bond, and the dashed line indicates either saturation or c-d or d-e unsaturation; R^ , which are the same or different, is the alkylene of 1-4 carbon atoms, n, which are equal or different, are .0 or 1; Z is where R is hydrogen, aminoethyl or aminopropyl; hydroxyalkyl of 1-4 carbon atoms, dihydroxyalkyl of 2-4 carbon atoms; and R^ is hydrogen, hydroxyalkyl with 1-4 carbon atoms, or dihydroxyalkyl with 2-4 carbon atoms,'- Y is either or -R^- where R 2 is 2-hydroxy-1, 3-trimethylene, or R 1 as indicated above; R^ is hydrogen. alkyl of 1-4 carbon atoms, aminoalkyl of 1-4 carbon atoms or hydroxyalkyl of 1-4 carbon atoms or dihydroxyalkyl of 2-4 carbon atoms; R 1 is 2-hydroxy-1, 3-trimethicone or R 1 as indicated above; or when R^ and R^ together are ethylene, R^ is also ethylene, and R^ is aminoethyl, aminopropyl or aminohydroxypropyl, and acid addition salts thereof. 2. Connection according to claim 1, characterized in that R' and R are hydrogen or methyl. 3. Compound according to claim 1 or 2, characterized in that R^ and R^ are hydrogen. 4. Compound according to claim 1 or 2, characterized in that R^ is aminoethyl, R 1 is ethylene and R 2 is hydrogen. 5. Compound according to claim 1 or 2, characterized in that R,- is aminopropyl, R 1 is trimethylene and R 2 is hydrogen. 6. Compound according to claim 1 or 2, characterized in that R^ is ethylene, and R^ and R^ together are ethylene. 7. Connection according to claims 1-3, characterized in that --R is aminoethyl. 8- Connection according to claims 1-3, characterized in that R is methyl. 9. Compound according to claims 1 - 3> characterized in that R 1 is 2-hydroxyethyl. 10. Compound according to claims 1 - 3, characterized in that R3 is hydro9.en- 11. Connection according to claim 1, characterized by 'that each A is a [3 .1.1 ] - bicyclic group. 12° Connection according to claim 11, characterized by n being 1. 13. Compound according to claim 11 or 12, characterized in that R 2 is ethylene, R 2 is hydrogen, R 3 is ethylene, R 3 is aminoethyl and R 3 is hydrogen. 14. Compound according to claim 11 or 12, characterized in that R,, and R^ are t rirhethylene, R 1 is hydrogen, and R 2 and R 3 are hydrogen. 15. Compound according to claim 1, characterized in particular in that it has formula I where each A, which is the same or different, is a [2.2.1]-bicyclic group of formula II, where R, R', . R^ , n and Z are as indicated above, and syreaddis ion salts thereof. 16. Compound according to claim 15, characterized by . that R and R' are hydrogen or methyl, and less than 5 of the groups R and R' are methyl. 17. Connection according to claim 15, characterized in that A is [2.2.1]-bicycloheptenyl, and two R' on the neighboring carbon atom form an olefinic bond, and the other R" and R, which are the same or different, is hydrogen or methyl. 18. Compound according to claim 16 or 17, characterized in that ner 1. 19. Connection according to claim 15, characterized in that A is 3,3-dimethylnorborn-2-yl 20. Compound according to claim 15, characterized in that A is norborn-2-yl. 21. Compound according to claim 15, characterized in that Y is Rp is ethylene, R^ is hydrogen, R^ is ethylene, R^ is aminoethyl, and Rg is hydrogen. 22. Connection according to claim 15, characterized by atYer R2 and R3 are trimethylene, R3, R3 and R3 are hydrogen. 23. Compound according to claim 21 or 22, characterized in that each A is 3,3-dimethyl-norborn-2-yl. , 24. Compound according to claim 23, characterized in that R1 is ethylene. 25. Compound according to claim 23, characterized by • that R is methylene. 26. Connection according to claim 1, characterized in that it is 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,5,9-triazanonan-trihydrochlor id . 27. Connection according to claim 1, characterized in that it is 1-[1,5-di-(3,3-dimethylnorborn-2-yl)-3-pentyl]-1,4,7,10-tetraazadecane-tetra-hydrochloride. 28- Compound according to claim 1, characterized in that it is 1-[1,7-di-(5-norborneri-2-yl)-4-heptyl]-1,5,9-triazanonane-trihydrochloride. 29- Method for producing a compound according to claim 1, with the formula: where each A, which is the same or different, is a [2.2.1]-bicyclic group of the formula:a) or a [3.1.1]-bicyclic group with the formula:° ) where R, which is the same or different, is hydrogen or alkyl of 1-4 carbon atoms, R', which is the same or different, is hydrogen or alkyl of 1-4 carbon atoms, or R' on neighboring carbon atoms together form an olefinic bond, and the dashed one line indicates either saturation or c-d or d-e unsaturation; each R 1 , which is the same or different, is alkylene of 1-4 carbon atoms; each n, which is equal or different, is 0 or 1; Z is where R 1 is hydrogen, aminoethyl or aminopropyl; hydroxyalkyl of 1-4 carbon atoms or dihydroxyalkyl of 2-4 carbon atoms; and R 1 is hydrogen, hydroxyalkyl of 1-4 carbon atoms or dihydroxyalkyl of 2-4 carbon atoms; Y is or -R^ - where where R 2 is 2-hydroxy-1,3-trimethylene or R as previously indicated; R^ is hydrogen, alkyl with 1-4 carbon atoms,. aminoalkyl with 1-4 carbon atoms or hydroxyalkyl with 1-4 carbon atoms or dihydroxyalkyl with 2-4 carbon atoms; R 1 is 2-hydroxy-1,3-trimethene or R 2 as previously indicated; or when R^ and R^ together are ethylene, R^ is also ethylene, and R^- is aminoethyl, aminopropyl or aminohydroxypropyl, and acid addition salts thereof, characterized in that a compound of formula I is reduced.