Alicyclic alkylene polyamine microorganism and algae growth inhibitors

Novel dicyclohexyl, dicyclohexenyl and cyclohexylcyclohexenylalkyl polyamines are useful antimicrobial agents, as well as algae inhibitors. They are especially useful in agriculture to protect plants against diseases such as leaf, stem, and fruit spotting, internal discoloration and decay of fruits and vegetables. These compounds are particularly active against diseases caused by the genera Pseudomonas, Xanthomonas, Erwinia, and Corynebacterium.

DISCLOSURE OF THE INVENTION 
This invention relates to a new class of substituted polyamines which are 
useful as algae inhibitors and as broad spectrum antimicrobial agents, 
especially against bacteria causing plant diseases. The novel compounds of 
this invention have the structural formula: 
##STR1## 
where A is independently a cyclohexyl of C.sub.1 to C.sub.6 alkyl 
substituted cyclohexyl, or an unsubstituted or C.sub.1 to C.sub.6 alkyl 
substituted cyclohexenyl of the formula: 
##STR2## 
where each R is either hydrogen or C.sub.1 to C.sub.6 alkyl and the dashed 
line indicates either saturation or a single olefinic bond in the ring and 
provided that if A is cyclohexenyl, no more than 9 of R are C.sub.1 to 
C.sub.6 alkyl. 
Most suitably, less than five of R are C.sub.1 to C.sub.6 alkyl and 
preferably the total of carbon atoms in all of the R groups does not 
exceed eight. Most preferably, only three of the R groups are C.sub.1 to 
C.sub.4 alkyl, and as such are desirably methyl or ethyl. 
Each n is alike or different and is the integer 0 or 1; 
Each R.sub.1 is alike or different and is C.sub.1 to C.sub.4 alkylene; 
##STR3## 
R.sub.5 is hydrogen, aminoethyl, aminopropyl, C.sub.1 to C.sub.4 
hydroxyalkyl, or C.sub.2 to C.sub.4 dihydroxyalkyl; and 
R.sub.6 is hydrogen, C.sub.1 to C.sub.4 hydroxyalkyl or C.sub.2 to C.sub.4 
dihydroxyalkyl; and 
Where Y is 
##STR4## 
R.sub.2 is 2-hydroxy-1,3-trimethylene, or R.sub.1 as previously defined; 
R.sub.3 is hydrogen, C.sub.1 to C.sub.4 alkyl, C.sub.2 to C.sub.4 
aminoalkyl or C.sub.1 to C.sub.4 hydroxyalkyl, C.sub.2 to C.sub.4 
dihydroxyalkyl, e.g., 2,3-dihydroxypropyl and 3,4-dihydroxybutyl; 
R.sub.4 is 2-hydroxy-1,3-trimethylene, or R.sub.1 as previously defined; 
or when R.sub.3 and R.sub.6 taken together are ethylene, R.sub.4 is also 
ethylene, and R.sub.5 is aminoethyl, aminopropyl, or aminohydroxypropyl; 
When Y is 
##STR5## 
R.sub.7 is R.sub.2, methylene, or a chemical bond between the cyclohexylene 
moiety and a first nitrogen; R.sub.8 is R.sub.4 methylene or a chemical 
bond between the cyclohexylene moiety and a second nitrogen; 
When Y is --R.sub.2 --, R.sub.2, R.sub.5 and R.sub.6 are as previously 
defined. Most suitably R.sub.3, R.sub.5 and R.sub.6 are not simultaneously 
dihydroxyalkyl, and when R.sub.3, R.sub.5 and R.sub.6 are simultaneously 
dihydroxyalkyl, it is preferable that they are C.sub.3 or C.sub.4 
dihydroxyalkyl. 
Preferred polyamines I are those where the sum of the carbon atoms in both 
of R.sub.1 are from 2 to 8. 
The utility of the compounds of our invention is generally their broad 
spectrum antibacterial and antifungal properties. Especially useful is 
their activity against bacteria and fungi responsible for stunting the 
growth and even destruction of many types of crop-producing plants, and 
for those causing the degradation and deterioration of many types of 
materials. This includes papers, leather, textiles, aqueous preparations 
such as latex paints, adhesives, resins, pigment dispersions and 
oleoresinous coatings whose films are particularly vulnerable to the 
destructive action of fungi. The large economic losses encountered in 
papermaking operations caused by the accumulation of bacterial and fungal 
slimes in various parts of the water system can be eliminated to a 
significant extent by the use of the compounds herein described. In 
agriculture, a severe problem faced in the raising of cotton, beans, corn 
and other crops is the loss of yield per acre due to the action of 
soilborne fungi on seed and on the roots of the young plants. Control or 
elimination of these losses can be accomplished by the use of the 
compounds herein described as soil disinfectants in accordance with the 
invention. They can also be used on foliage and trees for the control of 
bacterial and fungal diseases. 
They are especially useful as an agent active against bacterial disease of 
fruits such as fireblight. The prime agent presently useful is 
streptomycin, which is not only expensive but being an antibiotic useful 
in human medicine, its use in agriculture is regarded by some as a source 
of streptomycin resistant species of pathogens. 
The compounds of this invention are preferably prepared according to the 
following sequence of reactions: 
##STR6## 
where A, Z and n have their previously defined meanings, HX is a mono or 
polybasic organic or inorganic acid, where sufficient HX is provided to 
protonate at least one amino group of compound I. 
The preparation of polyamine I comprises the straightforward Schiff base 
reaction of the appropriate ketone IV and the appropriate amine V. 
If amine V has two primary amino groups, it can either be symmetrical or 
unsymmetrical. An amine V, which is a symmetrical amine, e.g., where 
R.sub.2 and R.sub.4 are alike when R.sub.5 and R.sub.6 are hydrogen; or 
where R.sub.2 and R.sub.4 are ethylene, R.sub.5 is aminoethyl, and R.sub.6 
is hydrogen; or where R.sub.2 is trimethylene when R.sub.5 is 
3-aminopropyl and R.sub.6 is hydrogen; forms a single Schiff base VI. This 
is because regardless of which terminal primary amino group of amine V 
reacts with ketone IV, the same product results. However, where amine V is 
unsymmetrical two products can result. One is Schiff base VI. The other 
products have the formula VI(a) when R.sub.5 and R.sub.6 are hydrogen; 
##STR7## 
or VI(b) when R.sub.5 is aminoethyl or aminopropyl: 
##STR8## 
where A, R.sub.1-6 and n are as previously defined. Note that both 
products VI(a) and VI(b) come within the scope of the definition given for 
Schiff base VI. Where Schiff bases of formulas VI amd VI(A) or VI(b) are 
produced they can be separated, if desired, by the usual and well known 
separation techniques, i.e., distillation and the like. 
As an alternative to obtaining a mixture of Schiff bases VI and VI(a) or 
VI(b), the reaction can be conducted stepwise. For example, 
1,2-diaminoethane may be converted to a Schiff base with 
1,5-di-(4-isopropylcyclohexyl)-3-pentanone, catalytically reduced, then 
the ring nitrogen selectively cyanoethylated with acrylonitrile, followed 
by catalytic hydrogenation to furnish 
[1,5-di-(4-isopropylcyclohexyl)-3-pentyl]-1,4,8-triazaoctane. 
To prepare Schiff base VI, ketone IV and amine V are dissolved in a 
suitable inert solvent, for example, toluene, and heated to reflux, until 
reaction is substantially complete. Usually 5 to 20 hours is sufficient 
for water removal by azeotropic distillation. The solvent is then removed 
under reduced pressure and the residue comprising the 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 or chemically 
reduced. 
If reduction is catalytic, any unsaturated carbon to carbon bond in A will 
also be reduced or hydrogenated, as well as the carbon to nitrogen bond of 
the Schiff base VI. In such catalytic reductions, hydrogen saturates an 
alkanol solution of Schiff base VI using agitation in the presence of the 
usual hydrogenation catalysts, such as transition metals and their 
reducible oxides. Especially effective catalysts are the noble metals and 
their oxides. A particularly preferred catalyst is platinum oxide. 
Generally, the hydrogenation reaction is carried out in a manner well 
known in the art. Small particles, e.g., 100-300 mesh of catalyst are 
admixed with the Schiff base and excess amine in alcohol and placed in a 
closed system pressurized with from 3-5 atmospheres of hydrogen gas 
preferably at ambient temperature, and generally at such pressures and a 
temperature of from 15.degree. to 45.degree. C. At higher temperatures the 
pressure preferably need not exceed 15 atmospheres. After reaction is 
complete, the pressure is released and the catalyst separated from the 
reaction mixture by filtration. The filtrate containing the cyclohexyl 
polyamine I, is then further purified by usual techniques. Preferably, 
whatever solvent may be present is removed under reduced pressure, the 
residue then dissolved in a water-immiscible solvent, washed with water, 
followed by a further washing with a saturated aqueous inorganic salt 
solution. After drying, the solvent is removed by evaporation under 
reduced pressure giving the cyclohexylpolyamine I usually as an oil. The 
cyclohexylpolyamine can then be redissolved in loweralkanols, mixtures of 
loweralkanols and water, diethylether, dioxane and then neutralized with 
an acid, e.g., hydrogen chloride, or neutralized directly with aqueous 
acids. 
Acid addition salts are then isolated, if desired, by precipitation, 
evaporation or other usually employed techniques. 
Suitable anions X for the salt I(a) include anions derived from inorganic 
acids as well as those of organic acids such for example as halide, i.e., 
chloride, bromide or iodide or sulfate, nitrate, bisulfate, phosphate, 
acetate, propionate, maleate, succinate, laurate, palmitate, oleate, 
stearate, ascorbate, gluconate, citrate, carbonate, bicarbonate, benzoate, 
salicylate, pamoate, phthalate, furoate, picolinate, 
dodecylbenzenesulfonate, lauryethersulfonate, nicotinate and the like. 
Generally, any anion derived from an acid is suitable and satisfactory 
when the polyamine salt anion X.sup.-, e.g., chloride is replaced with 
other anions, by well known anion exchange techniques. 
When preparing cyclohexenylpolyamines, that is the product I where olefinic 
unsaturation in ring A is retained, a selective chemical rather than a 
catalytic reduction is employed to reduce Schiff base VI to product I. 
In this chemically reductive procedure, the ketone IV is reacted with the 
appropriate amine as before, but the Schiff base VI dissolved in an inert 
alkanol or ether-type solvent is reacted with a chemical reductant such as 
sodium borohydride or lithium aluminum hydride, respectively. 
Although as little as an equivalent of the chemical reductant can be used 
successfully, more satisfactory results are obtained if at least two molar 
excess of and preferably at least a 2.5 molar excess of the chemical 
reductant is employed. After any initial reaction has subsided, the 
reaction mixture of Schiff base VI and reductant may be heated to reflux 
for an hour or two, then cooled to room temperature, and afterwards 
concentrated under vacuum. The residue obtained is then further purified 
as by treatment with mineral acid or inorganic base as was described for 
polyamines I and the salt may thereafter be formed as previously 
described. 
The cyclohexyl and cyclohexenyl ketones IV are readily prepared and two 
alternative methods, are set forth below. 
A. The Condensation of Acids 
This method involves the following reaction scheme: 
##STR9## 
Acylative decarboxylation of acids VII is employed by heating the acid at 
elevated temperatures either with transition metals, preferably iron, 
transition metal oxides, alkaline earth oxides, with polyphosphoric acid 
or with boron trifluoride. Most suitably, acylative reaction is achieved 
by passage of acid vapors over catalysts such as heated thoria aerogel. 
Condensation-decarboxylation of an acid is the preferred method for 
preparing ketone IV when each A-(R.sub.1).sub.n group is alike, a mixture 
of products being obtained when several different acids are combined in a 
reaction. The preferred reaction comprises admixing carboxylic acid VII 
with reduced iron powder and stirring in an inert atmosphere at 
195.degree. to 200.degree. C. for 1-6 hours to form an iron salt. 
Preferably, the carboxylic acid VII and iron are agitated under an inert 
atmosphere of nitrogen for at least 2 hours at 195.degree. to 200.degree. 
C. 
After 2 hours, the temperature is increased suitably to 290.degree. to 
310.degree. C. and agitation continued for at least another 3 hour period, 
4 hours usually being sufficient. The reaction mixture is allowed to cool, 
and then is extracted with a suitable inert solvent such as diethylether 
and filtered. The solvent extracts are concentrated under reduced 
pressure. The residual liquid is distilled under vacuum to isolate the 
ketone IV. 
The carboxylic acids VII employed above are prepared by various means well 
known in the art. One particularly useful technique is the addition of a 
cyclohexene to an aliphatic acid anhydride. 
In this procedure, a mixture of the cyclohexene and a catalytic quantity, 
e.g., 0.2-0.3 mole for each mole of cyclohexene of a free radical-forming 
catalyst, such as di-tert-butyl peroxide, is added dropwise over 3-5 hours 
to a 5-15 molar excess of refluxing aliphatic acid anhydride. After 
complete addition, the reaction is heated at reflux for 5-10 hours, 
concentrated under reduced pressure and the liquid residue is mixed with 
aqueous sodium hydroxide and stirred with heating on a steam bath for 
about 2-5 hours. The cooled alkaline solution is then extracted with 
ether, the ether layer is discarded and the aqueous solution acidified, 
and then extracted well with ether. The combined ether extracts are washed 
with water, dried over anhydrous sodium sulfate, and concentrated under 
reduced pressure. The residual liquid or solid is distilled under vacuum 
to give the corresponding carboxylic acid, VII. 
Other carboxylic acids are readily obtained, for example, by the 
Diels-Alder reaction of a diene and alkyl substituted diene with various 
unsaturated aliphatic compounds or carboxylic acids, as are later referred 
to in greater detail. 
B. Condensation of a Grignard and a Nitrile 
Dicyclohexyl, dicyclohexenyl, or cyclohexyl-cyclohexenyl alkanones can be 
obtained according to the following reaction scheme: 
##STR10## 
where A or (R.sub.1).sub.n of each reactant may be the same or different 
and are as previously defined. 
This general procedure utilizes the reaction of a Grignard reagent prepared 
from a chloro- or bromo-substituted cyclohexane or cyclohexene derivative 
with a cyanosubstituted cyclohexane or cyclohexene derivative. The 
resultant disubstituted iminoalkane salt complex is hydrolyzed with 
aqueous mineral acid to the corresponding ketone. 
The Grignard reagent is obtained by reaction of the halide with magnesium 
metal, usually in the form of turnings of powder and may be catalyzed by 
very small concentrations of iodine or methyl iodide. Solvents which are 
useful include diethyl ether, dibutyl ether, tetrahydrofuran, dioxane and 
benzene. Usually, gentle warming suffices to initiate the reaction and the 
halide is gradually added to the metal-solvent mixture. After complete 
addition the disappearance of practically all magnesium metal signifies 
the end of the reaction. A small excess of halide is used and moisture 
must be excluded; a nitrogen atmosphere is beneficial. The Grignard 
reagent is then added to the nitrile which is previously dissolved in two 
or three times its volume of solvent over a period of 15 minutes to 1 hour 
at ambient The reaction mixture may then be heated to reflux to insure 
complete reaction. Generally, a small excess of Grignard reagent as 
compared to nitrile is employed. From 1 to 10 hours at reflux is 
sufficient for complete conversion. The resultant imine salt is preferably 
decomposed to the ketone with aqueous mineral acids such as hydrochloric, 
sulfuric and phosphoric. The ketones are water-insoluble and may be 
extracted with water-immiscible solvents. Purification is preferably 
accomplished by fractional distillation under reduced pressure. It is 
feasible to use the crude ketone reaction mixture for the alkylation of 
polyamines as the reaction by-products are usually alcohols or 
hydrocarbons and do not react with amines. The reactant halides, if 
present in the crude product, should be removed prior to the ketone-amine 
alkylation process. 
The concentrations of Grignard reagent and nitrile may be varied over wide 
limits for securing good yields in the process. 
The halide and cyano, as well as carboxylic derivatives of cyclohexanes and 
cyclohexenes are commonly available; where the requisite carboxylic, cyano 
or halo derivatives as used herein are not readily available they can be 
obtained through employing known techniques, for example, by means of the 
Dils-Alder synthesis: 
##STR11## 
where D is R, --(R.sub.1).sub.n --COOH, --(R.sub.1).sub.n --Br, or 
--(R.sub.1).sub.n --CN and where R.sub.1, R, and X have their previous 
meanings. Where D is R and each R is alkyl, the resulting cyclohexene can 
be reacted with an aliphatic acid anhydride as previously described. Where 
D is (R.sub.1).sub.n --COOH, (R.sub.1).sub.n --CN or (R.sub.1).sub.n --BR, 
the condensation can proceed as outlined in preparative examples A and B 
above. Of course, A(R.sub.1).sub.n --COOH can be treated by standard 
techniques with a phosphorous chloride, e.g., phosphorous pentachloride, 
to form A(R.sub.1).sub.n --COCl. 
Where R is independently either hydrogen or C.sub.1 to C.sub.6 alkyl, the 
Darzens synthesis [Compt. Rend., 150, 707 (1910)] can be used: 
##STR12## 
where R.sub.1, n, R and A are as previously defined. Likewise, the 
Blaise-Marie synthetic route can be employed [Bull. Soc. Chim. [4] 7, 215 
(1910) and Compt. Rend. 145, 73 (1907)]: 
##STR13## 
where A, n and R.sub.1 have their previously defined meanings. 
Once the ketone IV is obtained it can then be reacted with a suitable 
polyamine V. Polyamines V which are exceptionally suitable for reaction 
with ketone IV include diethylenetriamine, triethylenetetramine, 
3,3'-iminobis-(propylamine), 3,3'-methyliminobis-(propylamine), 
dipropylenetriamine, N,N'-bis-(3-aminopropyl)-1,3-trimethylenediamine, 
N,N'-bis-(2-aminoethyl)-1,3-trimethylenediamine, 
N,N'-bis-(3-aminopropyl)piperazine, 
N-(3-amino-2-hydroxypropyl)-1,3-trimethylenediamine, 
N-(2-aminoethyl)-1,3-trimethylene-diamine, 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, 
N,N'-bis-(3-aminopropyl)-1,4-cyclohexylene-bis-(methylamine), 
1-(2,3-dihydroxypropyl)-1,5,9triazanonane, 
1-(2-hydroxyethyl)-1,4,7,10-tetraazadecane, 
4-(3,4-di-hydroxybutyl)-1,4,8-triazaoctane, 
1-(2-hydroxypropyl)-5-hydroxymethyl-1,5,9-triazanonane, 
1,4-di-(3-aminopropyl)piperidine, tris-(3-aminopropyl)amine, 
ethylenediamine, trimethylenediamine, and 1,3-diamino-2-hydroxypropane. 
The compounds described herein are excellent broad spectrum antimicrobial 
agents which are especially effective against gram positive and negative 
bacteria, particularly the troublesome gram-negative of the genus 
Pseudomonas at aqueous concentrations of 1.0 to 100 ppm. Examples of 
susceptible species include, inter alia, Staphylococcus aureus, 
Streptococcus pyogenes, Bordetella bronchiseptica, Pasteurella multocida, 
Escherichia coli, Salmonella typhimurium, S. pullorum, Klebsiella 
pneumoniae, Aerobacter aerogenes, Pseudomonas aeruginosa, Desulfovibrio 
desulfuricans, Bacillus mycoides, fungi such as Aspercillus niger and 
Chaetomium globosum. For use, these compounds can be applied neat or 
employed in a diluted form. Satisfactory diluents include any inert 
material not destructive of the antimicrobial activity and especially 
liquid formulations comprising aqueous dispersions, solutions, and 
emulsions. Solid diluents include talc, corn starch, alumina and 
diatomaceous earth. The antimicrobial agents of this invention can also be 
deposed on materials such as natural fibers including paper, cotton, wool 
and synthetic fibers such as nylon, polypropylene, as well as upon 
inanimate surfaces including hard surfaces such as wood, glass, metal, 
tile, rubber, plastic, and porous surfaces such as concrete, leather and 
the like. 
The polyamines of this invention are especially useful in suppressing the 
growth of aerobic and anaerobic bacteria in fluids employed in cutting and 
grinding operations, such as metal working, and oil well drilling muds or 
secondary oil recovery waters and brines. Anaerobes such as the 
sulfate-reducer, Desulfovibrio desulfuricans, are inhibited at 0.1-10 ppm. 
concentration of these polyamines. Suppression of these bacteria 
eliminates hydrogen sulfide production and corrosion of equipment, 
plugging of oil-bearing sands, malodors and other deleterious actions. 
These compounds are also useful in the preservation against 
biodeterioration of other aqueous systems such as aqueous emulsions and 
dispersions, paints or coatings, pigment suspensions, adhesives and the 
like where proliferation of microorganisms can produce colloid breakdown, 
pH shifts, malodors, corrosive substances, viscosity loss and other 
undesirable effects. 
One particularly useful application of the compounds of this invention is 
imparting sanitizing properties to fabrics, either woven or non-woven, 
launderable or disposable which are to be employed, such for example, as 
diapers, surgical masks, caps, gowns, towels and drapes, covers for 
hospital furniture and instrument wrappings, aseptic facial tissues and 
sanitary napkins and bathroom tissue. In this application, the compounds 
of Formula I can be applied to the fibrous pulp before extracting or 
strand or thread formation or it can be sprayed upon the finished goods. 
Either deposition technique is satisfactory so long as from 1 .times. 
10.sup.-.sup.4 % or more by weight of the antimicrobial material is 
retained on the cloth. Greater than 0.1% to 1% by weight is generally 
excessive and superfluous. 
Another application is alone or in solution or suspension or in conjunction 
with soaps or detergents for use in cleansing the skin, particularly in 
presurgical scrubbing formulations, or in formulations for controlling the 
growth of Corynebacterium acnes. C. acnes is a strain of bacteria 
implicated in acne conditions, especially Acne vulgaris, wherein 
applications of as little as 1 to 5 ppm. is effective in controlling such 
skin dwelling bacteria. Larger concentrations can be used if desired 
without irritation or discomfort such as 2500 ppm and higher. Where the 
cleansing formulation is diluted with water upon use, the formulation can 
comprise from 0.01% by weight and more of the polyamine of this invention. 
In addition, the compounds described herein can be employed in impounded 
water, such as swimming pools, ponds or industrially-used water such as 
cooling or papermill water to inhibit growth of undesirable bacteria, 
fungi, and/or algae. 
In the control of slime-producing microorganisms and algae in recirculating 
industrial waters, particularly cooling operations and especially 
installations such as cooling towers, the polyamine compounds of this 
invention are usually employed alone, but can also be used in combination 
with other antimicrobial agents. The compounds are preferably employed as 
salts to enhance solubility. Concentrations in the recirculating water of 
as little as 1 .times. 10.sup.-.sup.4 % by weight are effective in 
inhibiting microbial growth. To insure effectiveness, especially against 
more resistant strains of microorganisms, and also when make-up water is 
added to replace water lost by evaporation and the like, concentrations of 
from 1 .times. 10.sup.-.sup.4 % to 5 .times. 10.sup.-.sup.2 % by weight 
are most satisfactory. Dosage may be continuous or as intermittent "shock 
treatment", i.e., addition in a 10-20 minute period every 4-8 hours. 
An unusual, highly advantageous property of these compounds is high 
substantivity to all kinds of surfaces; this provides protection against 
corrosion and acts as a storage depot for continuously dosing the waters 
in contact. The same properties also are largely responsible for the 
previously state utility as disinfectants for inanimate surfaces 
comprising walls and ceilings, equipment, animal pens, hospital 
facilities, kitchens and bathrooms and the like. 
In formulating the compounds of this invention for the above uses, these 
compounds can be employed in combination with other antimicrobial agents, 
surfactants, insecticides, defoamers, odorants, or as chelates of metals 
such as copper, calcium, magnesium and iron. 
AGRICULTURAL APPLICATIONS 
Wettable powder formulations for use as a dispersion in water represent a 
practical means for good distribution in soil. Other methods of achieving 
the same results include the preparation of dusts. All of the polyamines 
can be blended as fine powders with the commonly used powder diluents such 
as talc, clay, refined silicates, wood flour, sand, magnesium oxide, 
calcium carbonate, fuller's earth, kaolin, diatomaceous earth, mica, 
pumice and the like. The powder can have the following formulation: 
______________________________________ 
Percent 
______________________________________ 
Polyamine 1-75 
Inert diluent (clay, talc, etc.) 
25-99 
______________________________________ 
The mixtures may be finely powdered, e.g., to the 1-10 micron average 
particle size, or be made by blending the already finely powdered 
ingredients. 
For application as agricultural disinfectants the dusts may be applied to 
the seed and surrounding soil at the time of planting. The concentration 
of the sterilant is adjusted to give an effective, nonphytotoxic dosage in 
the soil. In general, the soil concentration of polyamine should be from 
10 to 25 parts per million (of active ingredient). For most economical and 
effective use the dusts can be applied in bands of 6 to 8 inches centered 
on the rows just prior to seeding. The material can then be rototilled to 
a depth of several inches. This mode of treatment saves material and 
protects the root system of young plants against microbial attack. For the 
protection of a given crop, such as cabbage, the band spread of 
antimicrobial can vary from 8 inches for black root disease to 12-15 
inches for club root disease prevention. Similarly, the depth to which the 
fungicide should be distributed can vary from 2 to 6 inches. 
The wettable powders can be prepared by the addition of 0.1-5% of a wetting 
agent to the powder blends. Many dispersing agents are commercially 
available which are non-phytotoxic at the required concentrations. These 
may, for example, be alkali metal and amine salts of sulfated and 
sulfonated acids, alcohols, and oils, or polyethoxylated alkyl phenols, 
long chain fatty amine quaternary salts, partial fatty acid esters of 
polyhydric alcohols, etc. Some dispersants can be used in preparing 
emulsifiable concentrates of the polyamines in organic solvents. Many of 
these agents are available in solvent-soluble form. The manner of 
application to the soil is similar to the dusts. Spray equipment is used 
to spread the suspensions or emulsions over the soil and by discing, the 
fungicidal agents can be uniformly distributed to varying depths. Spray 
application is also effective for band-limiting the dosages. 
Other agricultural uses for these formulations involve the eradication of 
bacterial blights of plants by application to the involved surface areas. 
The compounds of this invention show high orders of bacterial inhibition 
and are especially useful for this purpose. Some of the diseases which are 
of commercial importance in decreasing yield and quality and are 
controlled by the compositions of the invention are fire blight of apple 
and pear, bacterial spot on stone fruit, cherry leaf spot, walnut blight, 
common blight of bean, bacterial spot of tomato and pepper, and potato 
seed piece decay. The effective concentration of polyamines required 
varies from 5-200 parts per million; they may be applied as dusts, powder 
dispersions in water as emulsions in water, or as aqueous dipping baths. 
Other plant diseases which can be controlled by treatment with these 
formulations are fungal in origin, such as the many kinds of powdery 
mildew and leaf scabs. 
For seed treatment, proportions as low as 1 to 4 ounces per hundred weight 
(550 to 600 pm on seed) are effective against various fungi. 
The compounds of the invention can be used in form of aqueous suspensions 
or emulsions, the base products being generally insoluble in water. For 
this type of formulation various powdered carriers can be employed to aid 
in achieving uniform distribution. Talc, fuller's earth, calcium silicate, 
calcium carbonate, clays and the like are admixed with the agent along 
with wetting and dispersing agents and sticking agents. For maximum 
chemical compatability those which are non-ionic in character are 
preferred. Other nonionic or cationic surfactants are also satisfactory. 
Additional applications for the compounds of this invention include 
inhibiting formation of dental plaque especially when used as an oral 
rinse, e.g., a mouth wash, or in combination with a toothpaste or tooth 
powder containing from 50-1,000 ppm. 
The following specific examples are further illustrative of our invention, 
but should not be construed as any limitation on the compound presented in 
formula I or the appended claims. 
PREATION A 
Free Radical Addition of Acetic Anhydride to .beta.-Pinene 
To 1,000 g. (10 moles) of refluxing acetic anhydride is added dropwise a 
mixture of 136 g. .beta.-pinene (1.0 mole) and 30 g. t-butyl peroxide (0.2 
mole) over a period of 2.5 hours. The reaction mixture is then heated at 
reflux for an additional 5 hours. The acetic anhydride is then removed 
under vacuum and the residue hydrolyzed by treatment with 40 g. NaOH in 
250 ml. water and 150 ml. ethanol. The mixture is heated at reflux for 2 
hours, then acidified with hydrochloric acid, extracted with ether and 
dried over sodium sulfate. The dried extracts are evaporated to leave a 
residue which is distilled under vacuum giving 43.1 g. (22%) of 
3-(4-isopropylcyclohexenyl)propionic acid having a b.p. 
135.degree.-137.degree. C. (0.3 mm.). 
PREATION B 
3-(4-Isopropylcyclohexyl)propionic Acid 
The unsaturated acid from the previous preparation is dissolved in ethanol 
and hydrogenated with PtO.sub.2 at room temperature and 40 psi hydrogen 
pressure. The platinum catalyst is filtered off and the ethanol removed 
under reduced pressure. The saturated product 
3-(4-isopropylcyclohexyl)propionic acid is obtained as a colorless liquid 
42.3 g. (97%). 
PREATION C 
Preparation of 1,5-Di-(4-Isopropylcyclohexyl)-3-pentanone 
3-(4-Isopropylcyclohexyl)propionic acid (39.7 g., 0.20 mole) and iron 
(hydrogen reduced, 6.15 g., 0.11 mole) is heated for 1.5 hours at 
195.degree. C. under a nitrogen atmosphere. After that time, the 
temperature is increased to 290.degree. C. and maintained at that 
temperature for three hours. The cooled reaction mass is extracted well 
with ether, filtered through Celite, and the ethereal extracts 
concentrated under vacuum. The residue is stripped under vacuum to leave 
the product, 17.3 g. (51%). 
Similarly in an analogous manner there are obtained the following ketones. 
1,9-Dicyclohexyl-5-nonanone; 
1,5-Dicyclohexyl-3-pentanone; 
1,3-Dicyclohexylacetone; 
1,7-Dicyclohexyl-4-heptanone; 
1,3-Di-(3-methylcyclohexyl)acetone; 
1,7-Di-(4-ethylcyclohexyl)-4-heptanone; 
1,5-Di-(2-isopropylcyclohexyl)-3-pentanone; 
1,9-Di-(2-ethylcyclohexyl)-5-nonanone; 
1,5-Di-(4-t-butylcyclohexyl)-3-pentanone; 
1,5-Di-(2,4,6-trimethylcyclohexyl)-3-pentanone; 
1,5-Di-(3,5-diethylcyclohexyl)-3-pentanone; 
1,7-Di-(2,6-dimethyl-4-t-butylcyclohexyl)-4-heptanone; 
1,7-Di-(2,3,4,5,6-pentamethylcyclohexyl)-4-heptanone; 
when unsaturated acids are subjected to the above procedure the following 
representative ketones are obtained: 
1,7-Dicyclohex-3-enyl-4-heptanone; 
2,8-Di-(4-methylcyclohex-3-enyl)-5-nonanone and 
1,5-Di-[4-isopropylcyclohex-1-enyl]-3-pentanone. 
PREATION D 
Preparation of 4-Cyclohexyl-1-(4-isopropylcyclohexyl)butanone-2 
A Grignard reagent was prepared from 2-cyclohexylethyl bromide 21 gm. (0.11 
mole) and magnesium, 2.4 g. (0.1 gram atom). The magnesium is covered with 
25 ml. of anhydrous ether, a crystal of iodine added and in a nitrogen 
atmosphere, the halide dissolved in 50 ml. of anhydrous ether is added, 
once initial reaction is obtained, at reflux temperature over a period of 
1-2 hours. After complete addition, refluxing is continued for 1/2 hour. 
In a nitrogen atmosphere, the Grignard solution is clarified by passage 
through a glass wool filter plug and added slowly to an agitated solution 
of 4-isopropylcyclohexylacetonitrile, 14.9 gm. (0.09 mole) in 200 ml. of 
anhydrous diethyl ether. A gentle reflux is maintained during the addition 
which requires 1/2 to 1 hour. After complete addition and an additional 15 
minutes at reflux, the reaction mixture is cooled and poured onto a 
mixture of 50 ml. of concentrated hydrochloric acid and 200 gms. of ice 
using good mixing. Upon warming the ether is removed by distillation and 
the residue heated at 70.degree.-100.degree. C. for 1 hour. The product is 
extracted with two portions, 250 ml. each of ether, the ether solution 
dried over anhydrous magnesium sulfate and the solvent removed. Any of the 
reactants, i.e., halide and nitrile, are separated from the ketone by 
fractional distillation under reduced pressure along with by-products. 
In a similar procedure, the following ketones are prepared: 
1-(2-Methylcyclohexyl)-4-cyclohexylpentan-2-one; 
1-(4-t-Butylcyclohexyl)-5-(4-isopropylcyclohexyl)pentan-3-one; 
2-(3-Methylcyclohexyl)-8-(2-isopropylcyclohexyl)octan-4-one; 
1-(2,6-Dimethyl-4-t-butylcyclohexyl)-5-(3,5-diethylcyclohexyl)pentan-3-one. 
PREATION E 
Preparation of N-(3-Aminopropyl)-1,4-cyclohexanebis(methylamine) 
Acrylonitrile (26.5 g., 0.5 mole) is added dropwise over a 45 minute period 
to 1,4-cyclohexanebis(methylamine) (2.84 g., 2.0 mole) with stirring and 
ice bath cooling. After complete addition, the reaction mixture is stirred 
an additional 1 hour at 5.degree. C., gradually warmed to 45.degree. C. 
and kept 2 hours at that temperature followed by 1 hour at 90.degree. C. 
The reaction mixture is stripped of any unreacted acrylonitrile and excess 
non-cyanoethylated bis(methylamine) starting material which was removed at 
an internal temperature of 110.degree. C. and 1 mm. The residue is then 
dissolved in 1.5 l. of ethyl alcohol (ammonia gas saturated) mixed with 50 
ml. of sponge nickel catalyst and hydrogenated at 150 psi. After removal 
of catalyst by filtration, the solvent and ammonia is stripped off and the 
triamine product purified by fractionation under reduced pressure. 
A higher homolog, N-(3-aminopropyl)-1,4-cyclohexanebis-(2-ethylamine) is 
synthesized using the above procedure with 
1,4-bis-(2-aminoethyl)cyclohexane prepared according to P. P. Garcia and 
J. H. Wood, J. Org. Chem., 26, 4167 (1961). Excess staring amine in this 
example may be separated from product at a boiling point of 
122.degree.-126.degree. C./1 mm. 
PREATION F 
Preparation of 
N-(3-Aminopropyl)-N'-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine) 
Acrylonitrile (10.6 g., 0.2 mole) is added dropwise over a 15 minute period 
to N-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine) (37.2 g., 0.4 mole) 
with stirring and ice bath cooling. After complete addition, the reaction 
mixture is stirred an additional 2 hours at 5.degree. C., allowed to 
gradually warm over a 1 hour period. heated 2 hours at 45.degree. C. and 
finally 1 hour at 90.degree. C. It is then fractionated under reduced 
pressure up to an internal temperature of 170.degree. C. The residue is 
dissolved in 200 ml. ethyl alcohol, cooled in an ice bath and saturated 
with ammonia gas at 0.degree. C. Approximately 5 ml. of sponge nickel 
catalyst (W. R. Grace Co., Davison Chem. Division) is added and the 
mixture shaken under hydrogen at 150 psi until no further hydrogen uptake. 
The catalyst is removed by suction, filtration under nitrogen, the solvent 
stripped away and the residue fractionally distilled under reduced 
pressure. The trimaine product is readily distinguished from 
cyanoethylated diamine by its lower R.sub.f on silica gel using a solution 
of 1 volume concentrated aqueous ammonium hydroxide in 4 volume methyl 
alcohol. The synthesis is an adaptation of the method of M. Israel et al, 
J. Med. Chem., 7, 710 (1964) for the preparation of 
polymethylenepolyamines. 
PREATION G 
Preparation of N-(2-Hydroxyethyl)-1,4-cyclohexanebis(methylamine) 
A solution of 14.2 gm. (0.1 mole) of 1,4-cyclohexanebis(methylamine) in 150 
ml. anhydrous methyl alcohol and under an atmosphere of nitrogen is warmed 
to 45.degree.-50.degree. C. In a 20 minute period, there is introduced 
with good agitation and beneath the liquid surface a total of 1.1 gm. 
(0.025 mole) of ethylene oxide in gaseous form. The reaction temperature 
is maintained at 45.degree.-50.degree. C. for an additional one-half hour 
after stopping the addition of ethylene oxide. The methyl alcohol is 
removed by distillation at atmospheric pressure; excess 
1,4-cyclohexanebis(methylamine) is readily separated from the product by 
fractionation under reduced pressure. Only monoethoxylated compound 
remained and could be used as such or further purified by distillation at 
reduced pressure. 
PREATION H 
Preparation of N-(3-Amino-2-hydroxypropyl)-1,4-cyclohexanebis(methylamine) 
1,4-Cyclohexanebis(methylamine) (14.2 g., 0.1 mole) is dissolved in 50 ml. 
of anhydrous methyl alcohol and the solution cooled to +5.degree. C. in an 
ice bath. Epichlorohydrin (9.3 g., 0.1 mole) is added in a 2-minute period 
and the temperature maintained at +5.degree. C. for 2 hours; reaction is 
allowed to continue at 10.degree.-15.degree. C. until thin layer 
chromatography of an aliquot (silica gel plate with development using a 
solution of 1 volume concentrated aqueous ammonium hydroxide in 4 volumes 
of methyl alcohol) indicated nearly complete conversion of the starting 
diamine to the propylene chlorohydrin. The solution is then added to 100 
ml. of dry methyl alcohol previously saturated at 0.degree. C. with dry 
ammonia gas by continuous dropwise flow at +5.degree. C. with good 
agitation and external cooling. After stirring 2 hours at +5.degree. C., 
it is allowed to warm to 20.degree. C. and mixed overnight. The reaction 
is competed by heating at 45.degree.-55.degree. C. for 6 hours. The 
solvent and ammonia was removed by stripping and the product purified 
using fractional distillation under reduced pressure. 
N-(2,3-Dihydroxypropyl)-1,4-cyclohexanebis(methylamine) is produced by 
alkaline hydrolysis of the above propylenechlorohydrin derivative. 
The propylene chlorohydrin derivative is dissolved in a 1M sodium hydroxide 
solution containing 50% methyl alcohol and 50% water by weight in a ratio 
of 5 grams of chlorohydrin to 25 ml. of sodium hydroxide solution. After 
stirring 24 hours at 20.degree. C. the methyl alcohol is removed by 
distillation and the oil which separates is extracted with 100 ml. of 
diethyl ether. The extract is washed with approximately 10 ml. of cold 
water, the ether layer dried over anhydrous sodium sulphate and then 
filtered. Removal of the ether by distillation leaves the product in good 
purity as an oil. 
PREATION I 
Preparation of N,N'-bis-(3-Aminopropyl)-1,4-bis-(2-aminoethyl)cyclohexane 
Acrylonitrile (10.6 g., 0.2 mole) is added dropwise over a 15 minute period 
to 1,4-bis-(2-amainoethyl)cyclohexane (17.0 g., 0.1 mole) cooled in an ice 
bath and with good stirring. The resultant solution is maintained at 
5.degree.-10.degree. C. with agitation for 1 hour, allowed to warm to 
25.degree. C. over a 2 hour period and finally heated at 90.degree. 
C.-95.degree. C. for 4 hours. The reaction mixture is then freed of any 
unreacted material and monocyanoethylated product by gradually heating to 
an internal temperature of 130.degree. C. at a pressure of 0.5-1 mm. The 
residue is dissolved in 200 ml. ethyl alcohol which had been previously 
saturated with dry ammonia gas at 0.degree. C., mixed with approximately 5 
ml. of a sponge nickel catalyst suspension and reduced with shaking under 
200 psi hydrogen. The catalyst is removed by suction filtration, the 
filtrate stripped of solvent and the residue purified by fractional 
distillation under reduced pressure. 
PREATION J 
Preparation of N-(2-Aminoethyl)-1,4-bis-(2-aminoethyl)cyclohexane 
1,4-Bis-(2-aminoethyl)cyclohexane (68 gm., 0.4 mole) and ethyleneimine (4.3 
gm., 0.1 mole) with 0.4 g. ammonium chloride are mixed in a glasslined 
pressure reactor and filled with nitrogen to 100 psi. The mixture is 
shaken and heated at 85.degree.-95.degree. C. for 48 hours. After cooling, 
it is distilled rapidly free of the salt and then fractionated under high 
vacuum. The starting diamine is readily distinguished from the triamine 
product by thin layer chromatography on silica gel using a mixture of 1 
volume concentrated aqueous ammonium hydroxide with 4 volume methyl 
alcohol, the diamine having a much higher R.sub.f. 
PREATION K 
N,N-Bis-(3-hydroxypropyl)-1,4-cyclohexanebis(methylamine) 
Preparation of 1-Cyano-4-[di-(3-hydroxypropyl)aminomethyl]cyclohexane and 
catalytic reduction 
a. 1-Bromomethyl-4-cyanocyclohexane (20.2 g., 0.1 mole) and 
di-(3-hydroxypropyl)amine (53.2 g., 0.4 mole) in 400 ml. of anhydrous 
isopropyl alcohol are heated in an autoclave at 105.degree.-115.degree. C. 
for 8 hours with continuous agitation. The reaction mixture is stripped of 
solvent under reduced pressure and the residue diluted with 500 ml. of ice 
water. A cold solution of 5 g. of sodium hydroxide in 100 ml. of water is 
added and the mixture extracted with two 150 ml. portions of methylene 
chloride. The organic phase is then washed with 50 ml. of ice water, dried 
overnight with anhydrous sodium sulfate, filtered and freed of solvent by 
distillation under reduced pressure. 
b. The residual oil from a.) is taken up in 200 ml. of anhydrous ethyl 
alcohol previously saturated at 0.degree. C. with dry ammonia gas, mixed 
with 5 ml. of sponge nickel catalyst suspension and hydrogenated at 
25.degree. C. under 100 psi hydrogen pressure in a stirred autoclave. The 
reaction completion is readily determined by disappearance of the C.tbd.N 
IR absorption band and measurement of hydrogen uptake. The catalyst is 
removed by suction filtration, the solvent with mild heating under reduced 
pressure and the produce obtained pure with fractional distillation at 
reduced pressure. 
PREATION L 
N,N-Di-(2,3-dihydroxypropyl)trimethylenediamine 
Bis-(2,3-dihydroxypropyl)amine (16.5 g., 0.1 mole) and acrylonitrile (6.4 
g., 0.12 mole) was mixed in an ice bath and then warmed to room 
temperature. After standing for 2 hours, the mixture was then heated at 
45.degree.-55.degree. C. for 3 hours. The excess acrylonitrile was removed 
by gentle warming under reduced pressure. The residue was taken up in 
ethyl alcohol, mixed with sponge nickel catalyst and hydrogenated under 
200 psi hydrogen using good agitation. After filtration of catalyst the 
solvent and excess acrylonitrile was removed by stripping under reduced 
pressure to leave the product as an oil. 
PREATION M 
N,N,N'-Tri-(2,3-dihydroxypropyl)trimethylenediamine 
N,N-di-(2,3-dihydroxypropyl)trimethylenediamine (11.1 g., 0.05 mole) was 
dissolved in 125 ml. of methanol and heated under reflux with agitation. 
Glycidol (3.7 g., 0.05 mole) was added dropwise over a period of 1.5 hour 
and the solution mixed an additional hour at 60.degree.-80.degree. C. The 
methyl alcohol and other volatiles were removed by stripping under reduced 
pressure to leave the product suitable for use in the next steps. 
PREATION N 
5,9,9-Tri-(2,3-dihydroxypropyl)-1,5,9-triazanonane 
An aliquot of the residual oil from Preparation M (5.9 g., 0.02 mole) was 
mixed with acrylonitrile (2.75 g., 0.05 mole) at room temperature and then 
warmed at 50.degree.-60.degree. C. for 10-15 hours. The excess 
acrylonitrile was removed by stripping under reduced pressure and the 
residual oil taken up in 50 ml. of ethanol, mixed with 2 g. of sponge 
nickel catalyst and shaken under a hydrogen atmosphere of 200 psi for 6 
hours. The mixture was filtered free of catalyst and the solvent removed 
by distillation. The product could be brought to analytical purity by 
chromatography on a silica gel column and is an oil.

EXAMPLE 1 
Preparation of 1-[1,5-Di-(4-isopropylcyclohexyl)-3-pentyl]-1,5,9-triazanone 
1,5-Di-(4-isopropylcyclohexyl)-3-pentanone (6.70 g., 0.02 mole) and 
3,3'-iminobispropylamine (13.1 g., 0.10 mole) in 150 ml. toluene is heated 
at reflux overnight with a Dean-Stark water separator. The cooled solution 
is concentrated under reduced pressure. The residue is dissolved in 
ethanol and hydrogenated with PtO.sub.2 at room temperature and 40 psi 
hydrogen pressure. The platinum catalyst is filtered off and the ethanol 
removed under vacuum. The residual oil is dissolved in ether and the ether 
solution washed several times with water to remove the excess 
3,3'-iminobispropylamine. The ether extracts are dried over anhydrous 
sodium sulfate and concentrated under vacuum to leave the polyamine as a 
colorless oil. 
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 to leave the product as a solid which is digested 
with hot isopropyl alcohol. The solids are collected by filtration and 
dried under vacuum at 70.degree. C. to give a colorless product, 
1-[1,5-di-(4-isopropylcyclohexyl)-3-pentyl]-1,5,9-triazanone 
trihydrochloride. 
In an analogous manner, from the ketones and the amines set forth below, 
there are prepared the following compounds of this invention: 
TABLE I 
__________________________________________________________________________ 
Ketone Amine Product Melting Point 
__________________________________________________________________________ 
1,9-dicyclohexyl-5-nonanone 
3,3'-Iminobispropylamine 
1-[1,9-Dicyclohexyl-5-nonyl]- 
Dec 183.degree. - 187.degree. 
C. to 
1,5,9-triazanonane trihydro- 
pulp; 255.degree. - 267.degree 
. C. to 
chloride liquid 
1,5-Dicyclohexyl-3-pentanone 
Ethylenediamine 
N-[1,5-Dicyclohexyl-3-pentyl]- 
261.degree. - 263.degree. C. 
ethylenediamine dihydro- 
chloride 
1,5-Dicyclohexyl-3-pentanone 
N-(3-Aminopropyl)-N- 
1-[1,5-Dicyclohexyl-3-pentyl]- 
247.degree. - 249.degree. C. 
methyl-1,3-propane 
5-methyl-1,5,9-triazanonane 
diamine trihydrochloride 
1,3-Dicyclohexylacetone 
2-Hydroxy-1,3-diamino- 
N-[1,3-Dicyclohexyl-2-propyl]- 
Melts 200.degree. C. with 
propane 2-hydroxy-1,3-diaminopropane 
ening from 147.degree. C. 
dihydrochloride 
1,5-Dicyclohexyl-3-pentanone 
1,3-Diaminopropane 
N-[1,5-Dicyclohexyl-3-pentyl]- 
245.degree. - 250.degree. C. 
trimethylenediamine dihydro- 
chloride 
1,5-Dicyclohexyl-3-pentanone 
2-Hydroxy-1,3-diamino- 
1-Amino-3-[(1,5-dicyclohexyl)- 
250.degree. - 252.degree. C. 
propane 3-pentylamino]-2-propanol 
dihydrochloride 
1,7-Dicyclohexyl-4-heptanone 
Iminobispropylamine 
1-(1,7-Dicyclohexyl-4-heptyl)- 
260.degree. - 261.degree. C. 
1,5,9-triazanonane trihydro- 
chloride 
1,5-Dicyclohexyl-3-pentanone 
Iminobispropylamine 
1-(1,5-Dicyclohexyl-3-pentyl)- 
Dec. 224.degree. - 228.degree. 
C. to 
1,5,9-triazanonane trihydro- 
pulp; 242.degree. - 246.degree 
. C. to 
chloride liquid 
1,5-Dicyclohexyl-3-pentanone 
Triethylenetetramine 
1-(1,5-Dicyclohexyl-3-pentyl)- 
1,4,7,10-tetraazadecane 
__________________________________________________________________________ 
EXAMPLE 2 
Preparation of 
1-[1,5-Di-(4-isopropylcyclohexen-1-yl)-3-pentyl]-1,5,9-triazanonane 
1,5-(4-isopropylcyclohexen-yl)-3-pentanone, (6.60 g., 0.02 mole) and 
3,3'-iminobispropylamine (13.1 g., 0.10 mole) in 150 ml. of toluene is 
heated at reflux overnight with a Dean-Stark water separator. The toluene 
is then removed under vacuum. The residual oil dissolved in 25 ml. 
isopropanol is added dropwise to sodium borohydride (1.90 g., 0.05 mole, 
excess) suspended in 50 ml. isopropanol. After complete addition, the 
reaction mixture is heated at reflux for 1 hour. The isopropanol is 
evaporated under reduced pressure, the residue treated with water and the 
aqueous mixture extracted well with ether. The combined ether extracts are 
back-washed with water, a saturated sodium chloride solution, dried over 
anhydrous sodium sulfate and concentrated under vacuum to leave the 
polyamine product as a clear oil 7.4 g. (90%). 
The oil is dissolved in ether and the solution cooled in an ice-water bath. 
Hydrogen chloride gas is bubbled into the solution until no further 
precipitate is formed. The solid is collected by filtration, washed with a 
small amount of ether, and dried under vacuum to leave the polyamine 
trihydrochloride as a colorless product (96%), m.p. 
256.degree.-257.degree. C. 
In an analogous manner using the ketones and the amines set forth below the 
following compounds of this invention are prepared. 
TABLE II 
__________________________________________________________________________ 
Ketone Amine Product Melting 
__________________________________________________________________________ 
Point 
1,7-Di-(cyclohex-3-enyl)-4- 
Iminobispropylamine 
1-[1,7-Di-(cyclohex-3-enyl)- 
222.degree. - 223.degree. 
C. 
heptanone 4-heptyl]-1,5,9-triazanonane 
trihydrochloride 
2,8-Di-(4-methylcyclohex- 
Iminobispropylamine 
1-[2,8-Di-(4-methylcyclohex- 
269.degree. - 271.degree. 
C. 
3-enyl)-5-nonanone 3-enyl)-5-nonyl]-1,5,9- 
triazanonane trihydrochloride 
1,5-Di-[4-(isopropyl)cyclo- 
Triethylenetetramine 
1-[1,5-Di-(4-isopropylcyclo- 
229.degree. - 230.degree. 
C. 
hex-1-enyl]-3-pentanone hex-1-enyl)-3-pentyl]-1,4,7, 
10-tetrazadecane tetrahydro- 
chloride 
2,8-Di-(4-methylcyclohex-3- 
Tris-(3-aminopropyl)- 
1-[2,8-Di-(4-methylcyclohex-3- 
enyl)-5-nonanone 
amine enyl)-5-nonyl]-5-(3-aminopropyl)- 
1,5,9-triazanonane 
1,7-Di(cyclohex-3-enyl)-4- 
1,4-Bis-(3-aminopropyl)- 
1-(3-Aminopropyl)-4-3-[1,7-di- 
heptanone piperazine (cyclohexen-3-yl)-4-heptylamino] 
propyl piperazine 
1,7-Di(cyclohex-3-enyl)-4- 
1,4-Di-(3-aminopropyl)- 
A mixture of 1-(3-aminopropyl)-4- 
heptanone piperidine [3-[ 1,7-di-(cyclohexen-3-yl-4- 
heptylamino]propyl]piperidine and 
1-[3-[1,7-di-(cyclohexen-3-yl-4- 
heptylamino]propyl]-4-(3-amino- 
propyl-piperidine 
1,5-Di-(4-isopropylcyclo- 
N,N'-bis-(2-aminoethyl)- 
1-[1,5-Di(4-isopropylcyclohexenyl)- 
hexenyl)-3-pentanone 
1,3-propanediamine 
3-pentyl]-1,4,8,11-tetrazaundecane 
__________________________________________________________________________ 
EXAMPLE 3 
1-[1,7-Di-(4-methylcyclohexyl)-4-heptyl]-1,4,8-triazaoctane 
A mixture of 1,7-di-(4-methylcyclohex-3-enyl)-4-heptanone (0.03 mole) and 
1,2-diaminoethane (12.0 g., 0.20 mole) in 250 ml. ethanol is heated at 
reflux overnight. The cooled reaction mixture is hydrogenated with 
PtO.sub.2 at room temperature and 40 psi hydrogen pressure. The platinum 
catalyst is filtered off and the ethanol removed under reduced pressure. 
The residual oil is dissolved in ether and the ether solution washed 
several times with water to remove the excess diaminoethane. The ether 
extracts are dried over anhydrous sodium sulfate and concentrated under 
vacuum to leave a colorless oil, 11.2 g. (100%). 
The oil is dissolved in 20 ml. tert-butanol and chilled to 
0.degree.-5.degree. C. in an ice-water bath. Acrylonitrile (1.75 g., 2.2 
ml., 0.033 mole) is added dropwise over a 5-minute period. The reaction 
mixture is allowed to warm up to room temperature and is then heated at 
60.degree. C. overnight. The t-butanol was removed under reduced pressure. 
The residual oil was dissolved in 150 ml. glacial acetic acid and 
hydrogenated with PtO.sub.2 at room temperature and 40 psi hydrogen 
pressure. The platinum catalyst is filtered off and the acetic acid 
removed under vacuum. The residue is dissolved in ether and made basic 
with 10% sodium hydroxide. The ether solution is washed with water, dried 
over anhydrous sodium sulfate and concentrated under reduced pressure to 
leave the product. 
In addition, the compounds of this invention set forth below are prepared 
by the reactions set forth in the previous examples. 
1-[1,9-Dicyclohexyl-5-nonyl]-1,5,8,12-tetrazadodecane from 
N,N'-bis-(3-aminopropyl)-1,2-ethanediamine and 
1,9-dicyclohexyl-5-nonanone; 
1-[1,5-Dicyclohexyl-3-pentyl]-10-(2-hydroxyethyl)-1,4,7,10-tetrazadecane 
from 1-(2-hydroxyethyl)-1,4,7,10-tetrazadecane and 
1,5-dicyclohexyl-3-pentanone; 
1-[1,5-Dicyclohexyl-3-pentyl]-4-(2-aminoethyl)-1,4,7-triazaheptane from 
tris-(2-aminoethyl)amine and 1,5-dicyclohexyl-3-pentanone; 
1-[1,5-Dicyclohexyl-3-pentyl]-5-(2-hydroxypropyl)-9-hydroxymethyl-1,5,9-tri 
azanonane from 1-hydroxymethyl-5-(2-hydroxypropyl)-1,5,9-triazanonane and 
1,5-dicyclohexyl-3-pentanone; 
EXAMPLE 4 
Preparation of 
1-[1,5-Di-(4-isopropylcyclohexyl)-3-pentyl]-5-(2,3-dihydroxypropyl)-1,5,9- 
triazanonane 
1,5-Di-(4-isopropylcyclohexyl)-3-pentanone (6.7 g., 0.02 mole) and 
3,3'-(2,3-dihydroxypropylimino)bispropylamine (20.5 g., 0.10 mole), 
obtained by the catalytic hydrogenation of dicyanoethylated glycerylamine) 
in 150 ml. of toluene is heated at reflux overnight with a Dean-Stark 
water separator. The cooled solution is concentrated under reduced 
pressure. The residue is dissolved in ethanol and hydrogenated with 
PtO.sub.2 at room temperature and 40 psi hydrogen pressure. The platinum 
catalyst is filtered off and the ethanol removed under vacuum. The 
residual oil is dissolved in ether and the ether solution washed several 
times with water to remove the excess 
3,3'-(2,3-dihydroxypropylimino)bispropylamine. The ether extracts are 
dried over anhydrous sodium sulfate and concentrated to leave the 
polyamine product as an oil. 
In a like manner and using analogous quantities, but employing 
N,N-di-(2,3-dihydroxypropyl)trimethylenediamine and 
5,9,9-tri-(2,3-dihydroxypropyl)-1,5,9-triazanonane instead of 
3,3'-(2,3-dihydroxypropylimino)bispropylamine there are prepared 
respectively 
N-[1,5-di-(4-isopropylcyclohexyl)-3-pentyl]-N'-di-(2,3-dihydroxypropyl)tri 
methylenediamine, and 
1-[1,5-di-(4-isopropylcyclohexyl)-3-pentyl]-5-(2,3-dihydroxypropyl) 
9-di-(2,3-dihydroxypropyl)-1,5,9-triazanonane. 
EXAMPLE 5 
Preparation of 
1-[1,5-Di-(4-isopropylcyclohexyl)-3-pentyl]-5-(2,3-dihydroxypropyl)-9-(1,3 
-dihydroxyl-2-propyl)-1,5,9-triazanonane 
1-[1,5-Di-(4-isopropylcyclohexyl)-3-pentyl]-5-(2,3-dihydroxypropyl)-1,5,9-t 
riazanonane (5.2 g., 0.01 mole) and 1,3-dihydroxyacetone (9 g., 0.1 mole) 
in 100 ml. of chloroform was heated at reflux with a water separator 
connected until 1.8 ml. of water was collected (8-12 hours). The 
chloroform and excess 1,3-dihydroxyacetone were removed by distillation 
under reduced pressure. The residual oil was taken up in 75 ml. of 
ethanol, mixed with 1 gm. of platinum oxide and hydrogenated at 40 psi 
hydrogen pressure with shaking at room temperature. The catalyst was 
removed by filtration and ethyl alcohol by distillation to leave an oil. 
The product could be purified by column chromatography using silica gel 
and development with methyl alcohol containing ammonium hydroxide. 
In an analogous manner but starting with 
1,7-di-(2,3-dimethylcyclohexyl-4-heptyl)ethylenediamine, instead of 
1-[1,5-di-(4-isopropylcyclohexyl)-3-pentyl]-1,5,9-triazanonane there is 
obtained 
N-[1,7-di-(2,3-dimethylcyclohexyl)-4-heptyl]-N'-(1,3-dihydroxy-2-propyl)et 
hylenediamine. 
EXAMPLE 6 
1-[1,7-Di-(4-methylcyclohexyl)-4-heptyl]-4,8,8-tri-(2,3-dihydroxypropyl)-1, 
4,8-triazaoctane 
1-[1,7-Di-(4-methylcyclohexyl)-4-heptyl]-1,4,8-triazaoctane (4.1 g., 0.01 
mole) was dissolved in 50 ml. of methanol and heated under reflux with 
agitation. Glycidol (15 g., 0.2 mole) was added dropwise over a period of 
1.5 - 2 hours. After complete addition, the reaction mixture was stirred 
an additional 2 hours at 90.degree.-100.degree. C. The methyl alcohol was 
removed by stripping under reduced pressure and excess glycidol by 
distillation at 1 mm pressure. The residue could be further purified by 
conversion to the trihydrochloride salt in ethyl alcohol with dry hydrogen 
chloride and fractional crystallization. The free base may then be 
liberated from its salt by resin ion exchange or neutralization with 
aqueous sodium hydroxide. 
In an analogous manner using the following dicyclohexyl polyamines, there 
are obtained the following products. 
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Dicyclohexyl Polyamine 
Product 
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1-[ 1,5-Di-(4-isopropylcyclo- 
1-[1,5-Di-(4-isopropylcyclo- 
hexyl-3-pentyl]-3,7-di- 
hexyl)-3-pentyl]-3,7-di- 
hydroxy-1,5,9-triazanonane 
hydroxy-5-(2,3-dihydroxy- 
propyl)-9,9-di-(2,3-dihydroxy- 
propyl)-1,5,9-triazanonane 
1-[1,5-Di-(4-isopropylcyclo- 
1-[1,5-Di-(4-isopropylcyclo- 
hexyl)-3-pentyl]-1,4,7- 
hexyl)-3-pentyl]-4-(2,3-di- 
triazaheptane hydroxypropyl)-7,7-di-(2,3- 
dihydroxypropyl)-1,4,7- 
triazaheptane 
1-[1,5-Di-(4-isopropylcyclo- 
N-[1,5-Di-(4-isopropylcyclo- 
hexyl)-3-pentyl]ethylene- 
hexyl)-3-pentyl]-N',N'-di-(2,3- 
diamine dihydroxypropyl)ethylenediamine 
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Also each of the respective ketones IV set forth in Preparations C and D 
when reacted with each of the individual amines set forth at page 12, 
lines 24-30 and page 13, lines 1-11, firstly, according to the method set 
forth in Example 1, and then second according to Example 2 produce the 
entire range of compounds described according to this invention as 
embodied in Formula I.