Cationic direct dyes

Abstract

The invention relates to cationic direct dyes of the formula I (1), wherein m and n are independently from each other 0 or 1, D is an aromatic or a cationic heteroaromatic group, which are further specified, K is an aromatic or heteroaromatic group, E.sub.1 and E.sub.2 are independently from each other CH or N, An is an anion and a is a number from 1 to 6 and R.sub.1 and R.sub.2 are independently from each other and further specified. The compounds show washfastness at hair-dying. ##STR00001##

Claims

1. Compounds of formula ##STR00112## wherein D is a cationic heteroaromatic group having a ##STR00113## K is an aromatic or group; R.sub.1 and R.sub.2 independently from each other are hydrogen; C.sub.1-C.sub.12alkyl; C.sub.1-C.sub.12alkyl, which is substituted by hydroxy; amino-C.sub.6-C.sub.10aryl; N(R.sub.6R.sub.7)C.sub.1-C.sub.8alkyl; N(R.sub.6R.sub.7)C.sub.1-C.sub.12alkyl, which is substituted by hydroxy or interrupted by NR.sub.9; C.sub.6-C.sub.10aryl; or R.sub.6, R.sub.7 and R.sub.9, independently from each other are hydrogen; C.sub.1-C.sub.5alkyl; amino-C.sub.1-C.sub.5alkyl; C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl; or di-C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl; R.sub.10 and R.sub.11 independently from each other are hydrogen; C.sub.1-C.sub.12alkyl; N(R.sub.13R.sub.14)C.sub.1-C.sub.12alkyl; N(R.sub.13R.sub.14)C.sub.1-C.sub.12alkyl which is interrupted by phenylene; N.sup.+(R.sub.13R.sub.14R.sub.15)C.sub.1-C.sub.12alkyl which is interrupted by phenylene; R.sub.13, R.sub.14, R.sub.15 independently from each other are hydrogen; C.sub.1-C.sub.5alkyl; amino-C.sub.1-C.sub.5alkyl; C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl; or di-C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl; E.sub.1 and E.sub.2 independently from each other are N; An is an anion a is a number from 1 to 3; m and n are 1; wherein for group D, at least one of the radicals R.sub.1, R.sub.2, R.sub.10, and R.sub.11 is substituted by radical comprising at least one amino group.

2. Compounds according to claim 1, wherein D in formula (1a) R.sub.10 and R.sub.11 independently from each other are C.sub.1-C.sub.12alkyl; amino-C.sub.1-C.sub.12alkyl; di-C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.12alkyl; or N.sup.+(R.sub.3R.sub.4R.sub.5)C.sub.1-C.sub.12alkyl.

3. Compounds according to claim 1, which correspond to formula ##STR00114## wherein R.sub.1 and R.sub.2 independently from each other are hydrogen; C.sub.1-C.sub.12alkyl; C.sub.1-C.sub.12alkyl, which is substituted by hydroxy; amino-C.sub.6-C.sub.10aryl; N(R.sub.6R.sub.7)C.sub.1-C.sub.8alkyl; N(R.sub.6R.sub.7)C.sub.1-C.sub.8alkyl, which is interrupted by NR.sub.9; R.sub.10 and R.sub.11 independently from each other are C.sub.1-C.sub.12alkyl; C.sub.1-C.sub.12alkyl which is substituted by hydroxy or interrupted by phenylene; amino-C.sub.1-C.sub.12alkyl; di-C.sub.1-C.sub.5alkyl-amino-C.sub.1-C.sub.12alkyl; or N.sup.+(R.sub.3R.sub.4R.sub.5)C.sub.1-C.sub.12alkyl; An is an anion; and R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.9 independently from each other are hydrogen; C.sub.1-C.sub.5alkyl; amino-C.sub.1-C.sub.5alkyl; C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl; or di-C.sub.1-C.sub.5alkylamino-C.sub.1-C.sub.5alkyl.

4. Compounds according to claim 1, wherein R.sub.1 and R.sub.2 independently from each other are C.sub.1-C.sub.12alkyl; R.sub.6, R.sub.7, R.sub.5, independently from each other are hydrogen; or C.sub.1-C.sub.6alkyl; and R.sub.10 and R.sub.11 independently from each other are C.sub.1-C.sub.12alkyl; or N.sup.+(R.sub.3R.sub.4R.sub.5)C.sub.1-C.sub.12alkyl; and R.sub.3, R.sub.4 and R.sub.5 independently from each other are hydrogen; or C.sub.1-C.sub.5alkyl.

5. Compounds according to claim 1, wherein R.sub.1 and R.sub.2 are hydrogen; or C.sub.1-C.sub.5alkyl; R.sub.6, R.sub.7, R.sub.5, independently from each other are hydrogen; or C.sub.1-C.sub.5alkyl; and R.sub.10 and R.sub.11 are C.sub.1-C.sub.5alkyl; or N.sup.+(R.sub.13R.sub.14R.sub.15)C.sub.1-C.sub.5alkyl; or N(R.sub.13R.sub.14)C.sub.1-C.sub.5alkyl; and R.sub.3 and R.sub.4 independently from each other are hydrogen; or C.sub.1-C.sub.5alkyl.

6. Compounds according to claim 1, wherein R.sub.1 and R.sub.2 independently from each other are C.sub.1-C.sub.12alkyl; and R.sub.11 and R.sub.12 independently from each other are C.sub.1-C.sub.5alkyl; or amino-C.sub.1-C.sub.5alkyl.

7. A compound selected from the group consisting of: ##STR00115## ##STR00116##

Description

EXAMPLES

Example 1: (E)-1,3-bis(3-aminopropyl)-2-((4-dimethylamino)phenyl)diazenyl)-1H-imidazol-3-ium bromide dihydrochloride

(1) ##STR00017##

Example 1

(2) ##STR00018##

a) Step 1: 4-[(E)-1H-imidazol-2-ylazo]-N,N-dimethyl-aniline

(3) ##STR00019##

(4) 20 g (0.105 mol) 2-((4-fluorphenyl)diazenyl)-1H-imidazole prepared according to literature (V. Eliu et al, WO2007025889) were suspended in 60 ml dimethylsulfoxide. To this suspension, 60 ml (0.532 mol) of an aqueous solution (40%) of dimethylamine was added within 10 minutes. The product mixture was heated to 80 C. and stirred at this temperature for 6 hours. Then the reaction solution was slowly cooled down to 20 C. A brown suspension was formed. The precipitate was filtered-off, washed with distilled water and dried at 40 C. at high vacuum.

(5) Yield: 14 g, yellow solid.

(6) .sup.1H NMR (DMSO-d.sub.6): =3.20 (s; 6H; 2H.sub.3), 6.80, 7.20 and 7.78 (each m; 2H; Aryl-H), 12.5 (s, br, NH) ppm.

b) Step 2: 2-((E)-(4-(dimethylamino)phenyl)diazenyl)-1,3-bis(3-((((1,1-dimethylethyl)oxy)carbonyl)amino)propyl)-1H-imidazol-3-ium bromide

(7) ##STR00020##

(8) 13.2 g (0.061 mol) 4-[(E)-1H-imidazol-2-ylazo]-N,N-dimethyl-aniline prepared in step 1a) were suspended in 240 ml dioxane and stirred at 25 C. To this suspension, 10.2 g (0.121 mol) sodium bicarbonate and 43.8 g (0.184 mol) tert-butyl N-(3-bromopropyl)carbamate were added. The reaction mixture is heated to 100 C. After 4 hours, another 25.6 g sodium hydrogencarbonate were added. The reaction mixture is kept at 100 C. for another 10 hours and then cooled down to 20 C.

(9) 700 ml of ethyl acetate were poured into the product mixture. The formed precipitate was filtered-off. The residue was suspended in 100 ml methanol and stirred at 20 C. for 1 hour. The solid residue was again collected by filtration, washed with 100 ml ethanol and dried at 40 C. at high vacuum.

(10) Yield: 37 g (74%), red solid.

(11) .sup.1H NMR (DMSO-d.sub.6): =1.31 (s; 18H, CH.sub.3), 1.93 (m; 4H, CH.sub.2), 3.0 (m; 4H, CH.sub.2), 3.24 and 3.35 (s; NCH.sub.3), 4.37 (m; 4H, CH.sub.2), 6.98 (m; 3H, Signals overlapping, Aryl-H and NH), 7.84 (s; 2H, Imidazoyl-H), 7.92 (m; 2H, Aryl-H) ppm.

c) Final Step

(12) 27 g (0.044 mol) of intermediate prepared in 1 b) were suspended in 30 ml water and stirred at 20 C. 200 ml of a 4N hydrochloric acid were slowly added within 5 minutes. The product mixture has been stirred at 20 C. for 4 hours. The obtained dark red solution was washed with 250 ml of 1-butanol. The aqueous phase was carefully evaporated in vacuum to give a dark violet raw product. It was suspended in 200 ml of ethyl acetate and stirred at 20 C. for two hours. The solid was collected by filtration, washed with ethyl acetate and dried in high vacuum at 40 C.

(13) Yield: 18 g (99%), red solid.

(14) UV .sub.max=540 nm.

(15) .sup.1H NMR (DMSO-d.sub.6): =2.16 (m; 4H, CH.sub.2), 2.87 (m; 4H, CH.sub.2), 3.25 (s; 6H, NCH.sub.3), 4.53 (br t; 4H, CH.sub.2), 6.98 (d; 2H, Aryl-H), 7.96 (s; 2H, Imidazoyl-H), 8.02 (d; 2H, Aryl-H), 8.26 (br; 6H, NH.sub.3) ppm.

Example 2: (E)-1,3-bis-(3-ammoniopropyl)-2-((4-(dipentylamino)phenyl)diazenyl)-1H-imidazol-3-ium trifluoracetate

(16) ##STR00021##

Synthesis Scheme of Example 2

(17) ##STR00022##

a) Step 1 1,3-bis(3-(1,3-dioxo-1,3-dihydro-2H-isoindole-2-yl)propyl)-2-((E)-(4-fluorophenyl)diazenyl)-1H-imidazol-3-ium bromide

(18) ##STR00023##

(19) To a mixture of 3.8 g (20 mmol) 2-((4-fluorphenyl)diazenyl)-1H-imidazole and 3.4 g (40 mmol) sodium bicarbonate in 80 ml of acetonitrile was added 16.1 g (60 mmol) N-(3-bromopropyl)phthalimide. The mixture was refluxed for 60 hours. The formed precipitate was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was applied to flash chromatography to yield intermediate as brown solid.

(20) Yield: 4.2 g (33%).

b) Step 2: 1,3-bis(3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl)-2-((E)-(4-dipentylaminophenyl)diazenyl)-1H-imidazol-3-ium bromide

(21) ##STR00024##

(22) To a mixture of 1.94 g (3 mmol) crude intermediate from example 2a), 4.5 g (1.5 mmol) sodium bicarbonate in 2.5 ml of acetone and 10 ml of water was added 0.566 g (3.6 mmol) dipentylamine. The mixture was stirred at 20 C. for 3 hours. The mixture was diluted with water and extracted with dichloromethane. The crude product was purified with flash chromatography.

c) Final Step

(23) 2.3 g (2.94 mmol) was dissolved in isopropanol and 1.8 g (29.4 mmol) ethylenediamine was added. The mixture was refluxed for 5 hours. The crude product was purified by prep. HPLC with 0.1% trifluoroacetic acid added to the liquid phases to yield target compound (220 mg) as dark powder.

(24) UV .sub.max=538 nm.

(25) .sup.1H NMR (DMSO-d.sub.6): =0.89 (t; 6H, CH.sub.3), 1.30-1.37 (m; 8H, CH.sub.2), 1.61 (m; 4H, CH.sub.2), 2.17 (m, 4H, CH.sub.2), 2.87 (m; 4H, CH.sub.2), 3.52 (t; 4H, CH.sub.2), 4.51 (t; 4H, CH.sub.2), 6.95 (d; 2H, Aryl-H), 7.99 (s; 2H, Imidazoyl-H), 7.99 (d; 2H, Aryl-H), 8.35 (br; 6H, NH.sub.3) ppm.

Example 3: (E)-2-((4-(bis(3-aminopropyl)amino)phenyl)diazenyl)-1,3-di-pentyl-1H-imidazol-3-ium bromide dihydro 2,2,2-trifluoroacetate

(26) ##STR00025##

Synthesis Scheme of Example 3

(27) ##STR00026##

a) Step 1: (E)-2-((4-(fluorphenyl)diazenyl)-1,3-di-pentyl-1H-imidazol-3-ium bromide (103a)

(28) To a solution of 2.85 g (15 mmol) 2-((4-fluorphenyl)diazenyl)-1H-imidazole in 60 ml acetonitrile at 20 C. was added 3.78 g (45 mmol) sodium bicarbonate and 6.8 g (45 mmol) 1-bromopentane. The resulting reaction mixture was heated to reflux for 60 hours. The mixture was filtered to remove solid and the filtrate was concentrated under reduced pressure. The residue was purified to flash chromatography.

(29) Yield: 1.6 g (25%), brownish solid.

(30) .sup.1H NMR (MeOD): =0.93 (t; 6H, CH.sub.3), 1.43 (m; 8H, CH.sub.2), 1.97 (m; 4H, CH.sub.2), 4.61 (m; 4H, CH.sub.2), 7.48 (m; 2H, Aryl-H), 8.00 (s; 2H, Imidazoyl-H), 8.22 (d; 2H, Aryl-H) ppm.

b) Step 2: (E)-2-((4-(bis(3((((1,1-dimethylethyl)oxy)carbonyl)amino)propyl)phenyl)diazenyl)-1,3-di-pentyl-1H-imidazol-3-ium bromide

(31) ##STR00027##
I)

Synthesis of di-tert butyl.(azanediylbis(propane-3,1-diyl))dicarbamate (1,9-bis boc 1,5,9-triazanonane)

(32) ##STR00028##

(33) To a mixture of 6.56 g (50 mmol) dipropylenetriamine, 7.08 g (70 mmol) triethylamine and 80 ml tetrahydrofuran at 0 C. was added a solution of 24.6 g (100 mmol) (2-tert.butoxycarbonylox-imino)-2-phenylacetonitrile in 20 ml tetrahydrofuran dropwise. After addition, the reaction mixture was warmed to 20 C. and stirred for another 12 hours. The reaction mixture was concentrated to remove tetrahydrofuran, and the residue was diluted with 200 ml dichloromethane. The mixture was washed with 40 ml sodium hydroxide solution (10%), 40 ml of water and 40 ml of saturated sodium chloride solution. After washing, the organic phase was dried with anhydrous magnesium sulfate and then concentrated to give the crude product (12.4 g, white solid). This crude product was used directly in the next step without further purification.

(34) II)

(35) To a mixture of 1.59 g (3.87 mmol) (E)-2-((4-(fluorphenyl)diazenyl)-1,3-di-pentyl-1H-imidazol-3-ium bromide, 0.49 g (5.81 mmol) sodium bicarbonate in 8 ml acetone and 2.5 ml water was added 1.41 g (4.26 mmol) of di-tert butyl.(azanediylbis(propane-3,1-diyl)) in 2 ml acetone. The mixture was stirred at 20 C. for 12 hours. The mixture was diluted with 10 ml water and extracted three times with 50 ml of dichloromethane. The organic layers were washed with water and brine, dried and concentrated under vacuum. The residue (2.75 g) was used in the next step without further purification.

c) Final Step

(36) To a solution of 2.74 g (3.80 mmol) from intermediate prepared in step 2 in 7 ml methanol was added 7 ml of 6M hydrochloric acid slowly. The resulting mixture was stirred at 20 C. for 2 hours. Then the mixture was heated to 60 C. for 2 additional hours. The reaction mixture was injected to preparative HPLC for purification with 0.1% trifluoro acetic acid added to the mobile phases. The liquid phases containing pure compound were collected and evaporated. The target molecule was isolated with trifluoracetate anions.

(37) Yield: 1.3 g (43% yield for two steps).

(38) .sup.1H NMR (MeOD): =0.93 (m; 6H, CH.sub.3), 1.3-1.5 (m; 8H, CH.sub.2), 1.89 (m; 4H, CH.sub.2), 2.12 (m; 4H, CH.sub.2), 3.12 (m; 4H, CH.sub.2), 3.77 (m; 4H, CH.sub.2), 4.49 (t; 4H, CH.sub.2), 7.11 (d; 2H, Aryl-H), 7.69 (s; 2H, Imidazoyl-H), 7.99 (d; 2H, Aryl-H) ppm.

(39) UV .sub.max=540 nm.

Example 4: (E)-2-((4-aminophenyl)diazenyl)-1,3-bis(3-aminopropyl)-1H-imidazol-3-ium trichloride

(40) ##STR00029##

Synthesis Scheme of Example 4

(41) ##STR00030##

a) Step 1: N-[4-[(E)-1H-imidazol-2-ylazo]phenyl]acetamide

(42) ##STR00031##
I)

(43) Preparation of diazo compound: 30.45 g (0.2 mol) p-aminoacetanilide was suspended in 400 ml water. 49.2 g concentrated hydrochloric acid (37%) were added and cooled down to 0-5 C. Within 30 minutes, 49.9 ml of an aqueous sodium nitrite solution (4M) were added. The suspension was stirred for 1 hour at 0 C. An excess of nitrite was destroyed by the addition of amidosulfonic acid.

(44) II)

(45) Coupling component: 13.66 g (0.2 mol) imidazole were dissolved in 400 ml of water and cooled to 0-5 C. The solution was adjusted to pH10 by addition of 30% sodium hydroxide solution.

(46) III)

(47) Coupling: The cooled diazosolution prepared in I) was added portion wise within 45 minutes to the imidazole solution. The temperature of the reaction solution was kept between 0-5 C.; pH 10 was adjusted by addition of sodium hydroxide. The yellow reaction suspension was stirred 1 hour at 0-5 C., then warmed up to 20 C. and stirred for another 10 hours. A pH of 9.5 was adjusted (sodium hydroxide). The formed precipitate was collected by filtration, washed with 600 ml of warmed (50 C.) distilled water and dried in vacuum at 20 C.

(48) Yield: 163 g, yellow solid.

(49) .sup.1H NMR (DMSO-d.sub.6): =2.10 (s; 3H, CH.sub.3); 7.30-7.8 (m; 6H, Aryl-H), 10.3 and 12.8 (s; br, each 1H, NH) ppm.

b) Step 2: 2-((E)-(4-(acetylamino)phenyl)diazenyl)-1,3-bis(3-((((1,1-dimethylethyl)oxy)carbonyl)amino)propyl)-1H-imidazol-3-ium bromide

(50) ##STR00032##
I)

Synthesis of N-(3-bromopropyl)-2,2,2-trifluoroacetamide

(51) ##STR00033##

(52) To a cooled stirred solution of 64.4 g (0.297 mol) 3-bromopropylamine hydrobromide in 840 ml methanol at 00 C. was added 44 ml (32.1 g, 0.317 mol) triethylamine. Within 30 minutes, 45.5 g (0.32 mol) ethyl trifluoroacetate was added to the above reaction mixture dropwise. The mixture was stirred at 00 C. for 3 hours. Solvent was evaporated under reduced pressure. The residue was taken up in 1400 ml of dichloromethane and was washed with water (360 ml), sodium bicarbonate solution (twice with 150 ml) and brine (400 ml). The organic solution was evaporated to dryness.

(53) Yield: 64 g (92%), colorless solid. This was used in the next step without further purification.

(54) .sup.1H NMR (CDCl.sub.3): =2.20, 3.47 and 3.63 (m; each 2H, CH.sub.2); 6.65 (s; br, NH) ppm.

(55) II)

(56) 5 g (0.022 mol) intermediate prepared in 4a) were suspended in 200 ml acetonitrile. 15.3 g (0.065 mol) N-(3-bromopropyl)-2,2,2-trifluoroacetamide prepared above were added to this suspension. The product mixture was heated to reflux (60 C.). Then 3.66 g (0.043 mol) sodium bicarbonate were added. The product mixture was kept under reflux for 70 hours. The warm suspension was filtrated. The mother liquor was evaporated in vacuum; the obtained solid was treated with 200 ml dichloromethane. 10 ml of methanol and 15 ml of ethyl acetate were added. The precipitate was collected by filtration and washed with 10 ml of dichloromethane. The raw product was suspended in 250 ml water, filtrated and evaporated by freeze-drying.

(57) Yield: 1.4 g (12%), dark orange solid.

(58) .sup.1H NMR (DMSO-d.sub.6): =2.0-2.2 (m; signals overlapping, 7H, CH.sub.3 and CH.sub.2), 3.33 (m, 4H, CH.sub.2), 4.50 (m; 4H, CH.sub.2), 6.95 (d; 2H, Aryl-H), 8.0-8.2 (m; signals overlapping, 4H, Aryl-H), 7.99 (d; 2H, Aryl-H, Imidazoyl-H), 9.59 (m; 2H, NHCF.sub.3), 10.71 (s, 1H, NHCO) ppm.

c) Step 3 (Final Step)

(59) 1.3 g (2 mmol) intermediate from 4b, II) was suspended in 26 ml hydrochloric acid (3M) and stirred for 3 hours at 90 C. The obtained product solution was evaporated in vacuum. Again, 26 ml hydrochloric acid was added, the obtained solution heated to 90 C. and kept at this temperature for 1 hour. Then, the solution was evaporated until dryness. The raw product is treated with small amount of dichloromethane, filtered-off and dried in high vacuum at 20 C.

(60) Yield: 350 mg (80%), red solid.

(61) UV .sub.max=498 nm.

(62) .sup.1H NMR (D.sub.2O): =2.23, 3.04 and 4.48 (m; 12H, CH.sub.2), 6.95 (m; 2H, Aryl-H), 7.11 (d; 2H, Aryl-H), 7.56 (s; 2H, Imidazoyl-H), 7.88 (d; 2H, Aryl-H) ppm.

Example 5: (E)-1,3-bis(3-N,N-dimethylaminopropyl)-2-((4-(dimethylamino)phenyl)-diazenyl)-1H-imidazol-3-ium bis-trifluoracetate

(63) ##STR00034##

Synthesis Scheme of Example 5

(64) ##STR00035##

a) Step 1: (E)-[1,3-bis(3-bromopropyl)imidazol-1-ium-2-yl]-(4-methoxyphenyl)diazene; bromide

(65) ##STR00036##

(66) 59.3 g (296.9 mmoles) dibromopropane and 12.47 g (148.45 mmoles) sodium bicarbonate were suspended in 100 ml of acetonitrile and heated to 70 C. 30 g (149 mmol) (E)-1H-imidazol-2-yl-(4-methoxyphenyl)diazene [prepared according to L. Skulski, D. Maciejewska, Polish J. Chem., 59 (1), 37 (1985)] was suspended in 100 ml acetonitrile and added in portions to the hot reaction mixture. The temperature was then raised to 90 C. and stirring was continued for 21 hours. The reaction mixture was then cooled to 25 C. and filtered. Evaporation of the filtrate provided 45 g of a black oil. The raw product was purified by column chromatography (silica gel, with 2% methanol in pure dichloromethane and increased 2% methanol every 2 liters until the product eluted with 6% methanol/dichloromethane). The product fractions were combined providing 0.90 g (8% yield) of the product.

b) Step 2 (Final Step)

(67) 870 mg of intermediate from step 1 (1.508 mmoles) was reacted with isopropanol (1 ml) and 40% ethanolic dimethyl amine solution (1.5 ml, 13.38 mmoles). The mixture was refluxed for 1 hour. The reaction was subsequently cooled and evaporated to dryness. The crude product was dissolved in 6 ml of water. Small portions of this solution, ranging from 0.5 ml to 2.0 ml, were purified by preparative HPLC (Column: Waters Xbridge Prep C.sub.18, 5 m, OBD 30250 mm). The pure fractions from each run were combined to provide 540 mg (58% yield) of target compound.

(68) .sup.1H NMR (CD.sub.3OD): =2.60 (dt; 4H, CH.sub.2); 2.92 (s; 12H, CH.sub.3), 3.32 (m; 10H, CH.sub.3, CH.sub.2), 4.55 (t; 4H, CH.sub.2), 7.00 (d; 2H, CH), 7.65 (s; 2H, HCCH), 8.03 (d; 2H, CH) ppm.

(69) ESI-MS m/z 386.35 [M.sup.+].

Example 6: 4-[(E)-[3-(3-aminopropyl)-1-methyl-imidazol-2-yl]azo]-N,N-dimethyl-aniline chloride

(70) ##STR00037##

Synthesis Scheme of Example 6

(71) ##STR00038##

a) tert-butyl N-[3-[2-[(E)-(4-fluorophenyl)azo]imidazol-1-yl]propyl]carbamate

(72) ##STR00039##

(73) 11.5 g (0.06 mol) 2-((4-fluorphenyl)diazenyl)-1H-imidazole and 16.9 g (0.122 mol) potassium carbonate were suspended in 300 ml of N,N-dimethylformamide. To that suspension, a solution of 18.7 g (0.074 mol) 3-(tert-butoxycarbonylamino)propyl methanesulfonate [prepared according to literature: Ganguli et al., Bioorg. Med. Chem. Lett. 24 (2014) 4198] in 100 ml of N,N-dimethylformamide was added within 10 minutes. The reaction mixture was heated to 110 C. for three hours. Afterwards the reaction mixture was poured into 500 g of ice. The reaction was stirred at 20 C. for 10 hours to become an orange suspension. The formed precipitate was collected by filtration (suction filter), washed with 500 ml of water and dried in high vacuum at 30 C. Yield: 17.2 g, yellow solid (82%).

(74) .sup.1H NMR (DMSO-d.sub.6): =1.32 (t; 9H, CH.sub.3), 1.95 (m; 2H, CH.sub.2), 4.41 (m; 2H, CH.sub.2), 6.90 (m; 1H, NH), 7.25 (m; 1H, Aryl-H), 7.40 (m; 2H, Aryl-H), 7.65 (s; 2H, Imidazoyl-H), 8.0 (m; 2H, Aryl-H) ppm.

b) Step 2: tert-butyl N-[3-[2-[(E)-(4-fluorophenyl)azo]-3-methyl-imidazol-1-yl]propyl]carbamate methyl sulfate

(75) ##STR00040##

(76) 12.4 g intermediate prepared in example 6a) was suspended in 150 ml of acetone and stirred at 20 C. 4.95 g (0.039 mol) dimethylsulfate is added dropwise within 20 minutes. The reaction mixture was stirred for 15 hours at 20 C. Then the solution was evaporated in vacuum and treated with 250 ml of distilled water. The pH was adjusted to 9 by addition of 1 M sodium hydroxide solution. The product was precipitated by addition of 250 ml brine. The formed precipitate was filtered-off and washed with brine. The raw product was suspended in ethanol, collected by filtration and dried in high vacuum at 30 C.

(77) Yield: 13.2 g (78%), orange solid.

(78) UV .sub.max=535 nm.

(79) .sup.1H NMR (DMSO-d.sub.6): =1.32 (t; 9H, CH.sub.3), 1.95 (m; 2H, CH.sub.2), 3.03 (m; 2H, CH.sub.2), 4.13 (s; 3H, CH.sub.3), 4.52 (m; 2H, CH.sub.2), 7.05 (m; 1H, NH), 7.56, 8.15 and 8.25 (m; each 2H, Aryl-H) ppm.

c) Step 3: tert-butyl N-[3-[2-[(E)-[4-(dimethylamino)phenyl]azo]-3-methyl-imidazole-1-yl]propyl]carbamate; methyl sulfate

(80) ##STR00041##

(81) Under stirring, 13.1 g (0.028 mol) intermediate prepared in 6b) was dissolved in 250 ml of acetonitrile. The solution was filtrated and 5.58 g (0.055 mol) triethylamine were added. Then, a solution of 5.28 g (0.039 mol) ethanolic dimethylamine (33%) was added dropwise within 5 minutes. The product mixture was stirred at 20 C. for 12 hours. Afterwards, the solvent was evaporated in vacuum to give 9.8 g (71%) of a violet solid which was directly used for the final step.

(82) .sup.1H NMR (D.sub.2O): =1.32 (t; 9H, CH.sub.3), 1.85 (m; 2H, CH.sub.2), 3.00 (m; 2H, CH.sub.2), 3.05 (s; 6H, CH.sub.3), 3.76 (s; 3H, CH.sub.3), 4.13 (m; 2H, CH.sub.2), 6.61 (d; 2H, Aryl-H), 7.25 and 7.31 (m; each 1H, Imidazoyl-H), 7.59 (d; 2H, Aryl-H) ppm.

d) Final Step

(83) To a stirred solution of 9.7 g (0.019 mmol) intermediate prepared in 6c) in 100 ml ethanol was added dropwise within 25 minutes 256 g of an ethanolic HCl-solution (2.5 M). The reaction solution was stirred at 20 C. for 72 hours. Afterwards, the solution was evaporated in vacuum, treated with 100 ml of distilled water and adjusted to pH8 by addition of sodium hydroxide solution (1M). The aqueous solution was freeze-dried to yield 9.8 g of a dark red solid which contained sodium chloride.

(84) .sup.1H NMR (D.sub.2O): =2.15 (m; 2H, CH.sub.2), 3.00 (m; 2H, CH.sub.2), 3.15 (s; 3H, CH.sub.3), 3.85 (s; 3H, CH.sub.3), 4.35 (m; 2H, CH.sub.2), 6.75 (d; 2H, Aryl-H), 7.31 and 7.38 (m; 1H, Imidazoyl-H), 7.76 (d; 2H, Aryl-H) ppm.

Example 7: 4-[(E)-[3-(5-aminopentyl)-1-methyl-imidazol-2-yl]azo]-N,N-dimethylaniline chloride

(85) ##STR00042##

Synthesis Scheme of Example 7

(86) ##STR00043##

a) Step 1: tert-butyl N-[5-[2-[(E)-(4-fluorophenyl)azo]imidazol-1-yl]pentyl]carbamate

(87) ##STR00044##

(88) Under stirring, 13.6 g (0.072 mol (E)-(4-fluorophenyl)-(1H-imidazol-2-yl)diazene and 18.2 g (0.0132 mol) potassium carbonate were suspended in 300 ml of N,N-dimethylformamide at 20 C. To that solution, a solution of 22.19 g (0.079 mmol) 3-(tert-butoxycarbonylamino)pentyl methanesulfonate (prepared from 1-aminopentanol in two steps according to literature cited in example 6) in 200 ml N,N-dimethylformamide were added dropwise within 10 minutes. The product mixture was heated to 110 C. and kept at that temperature for 4 hours. The reaction mixture was poured into 600 g of ice and stirred for 30 minutes. The formed precipitate was removed by filtration. The mother liquor was stirred at 20 C. for 12 hours. The formed orange precipitate was collected by filtration and dried in high vacuum. Yield: 20.2 g (75%), brownish solid.

(89) .sup.1H NMR (DMSO-d.sub.6): =1.24 (m; 2H, CH.sub.2), 1.39 (t; 9H, CH.sub.3), 1.42 (m; 2H, CH.sub.2), 1.81 (m; 2H, CH.sub.2), 2.87 (m; 2H, CH.sub.2), 4.39 (m; 2H, CH.sub.2), 6.74 (m; 1H, NH), 7.26 (s; 1H, Imidazoyl-H), 7.44 (m; 2H, Aryl-H), 7.61 (s; 1H, Imidazoyl-H), 7.96 (m; 2H, Aryl-H) ppm.

(90) UV .sub.max=535 nm.

b) Step 2: tert-butyl N-[5-[2-[(E)-(4-fluorophenyl)azo]-3-methyl-imidazol-1-yl]pentyl]carbamate methyl sulfate

(91) ##STR00045##

(92) Under stirring, 9.4 g (0.024 mol) intermediate from 7a) were dissolved in 150 ml acetone. The solution was treated with 3.5 g (0.028 mol) dimethylsulfate. The reaction and work-up was done according to the procedure described in example 6b).

(93) Yield: 13.7 g raw product which was used directly for the next step.

(94) .sup.1H NMR (DMSO-d.sub.6): =1.3-1.4 (m; signal overlapping, 13H, CH.sub.2 and CH.sub.3), 1.82 (m; 2H, CH.sub.2), 2.88 (m; 2H, CH.sub.2), 4.09 (s; CH.sub.3), 4.50 (m; 2H, CH.sub.2), 6.77 (m; 1H, NH), 7.58 (m; 2H, Aryl-H), 8.05 and 8.10 (s; each 1H, Imidazoyl-H), 8.21 (m; 2H, Aryl-H) ppm.

c) tert-butyl N-[5-[2-[(E)-[4-(dimethylamino)phenyl]azo]-3-methyl-imidazol-1-yl]pentyl]-carbamate methyl sulfate

(95) ##STR00046##

(96) A solution of 13.7 g (0.027 mol) crude intermediate from 7b) in 200 ml acetonitrile was treated with 5.55 g (0.055 mol) N,N-triethylamine and 5.24 g (0.038 mmol) of an ethanolic dimethylamine solution (33%). The reaction and work-up was done as described in example 6c.

(97) Yield: 18.5 g crude material.

(98) .sup.1H NMR (DMSO-d.sub.6): =1.25-1.45 (m; signal overlapping, 13H, CH.sub.2 and CH.sub.3), 1.75 (m; 2H, CH.sub.2), 2.89 (m; 2H, CH.sub.2), 3.23 (s; 6H, CH.sub.3), 3.96 (s; CH.sub.3), 4.39 (m; 2H, CH.sub.2), 6.76 (m; 1H, NH), 6.96 (m; 2H, Aryl-H), 7.75 and 7.80 (s; each 1H, Imidazoyl-H), 7.88 (m; 2H, Aryl-H) ppm.

d) Step 4 (Final Step)

(99) 24.2 g (0.046 mol) crude intermediate from 7c) in 250 ml ethanol was treated with 465 g ethanolic hydrochloric acid (2.5M). The reaction and work-up was done according to the procedure given in example 6d. Yield: 17.9 g, contained NaCl.

(100) .sup.1H NMR (D.sub.2O): =1.35, 1.58 and 1.77 (m; each 2H, 3CH.sub.2), 2.92 (m; 2H, CH.sub.2), 3.12 (s; 6H, CH.sub.3), 3.82 (s; 3H, CH.sub.3), 4.19 (m; 2H, CH.sub.2), 6.69 (d; 2H, Aryl-H), 7.20 and 7.25 (m; each 1H, Imidazoyl-H), 7.68 (d; 2H, Aryl-H) ppm.

Example 8: 4-[(E)-[1,3-bis(4-aminobutyl)imidazole-1-ium-2-yl]azo]-N,N-dimethyl-aniline bromide

(101) ##STR00047##

Synthesis Scheme of Example 8

(102) ##STR00048##

a) Step 1: 4-[(E)-[1,3-bis(4-bromobutyl)imidazol-1-ium-2-yl]azo]-N,N-dimethyl-aniline bromide

(103) ##STR00049##

(104) A mixture of 6.5 g (0.030 mol) 1,4-dibromobutane and 1.3 g (0.015 mol) sodium bicarbonate in 20 ml acetonitrile was heated to 65 C. Within 2 hours, a suspension of 1.0 g (0.005 mol) 4-[(E)-1H-imidazol-2-ylazo]-N,N-dimethylaniline prepared in example 1a) in 30 ml acetonitrile was added. The product mixture was heated to 85 C. and kept at this temperature for 12 hours. The production mixture was filtrated. The residue was suspended in acetonitrile for 30 minutes and again filtered-off. Both mother liquors were combined and evaporated in vacuum to give a dark red liquid. The raw product was crystallized with a mixture of acetonitrile/ethyl acetate. Yield: 1.24 g (47%) red sticky solid.

b) Step 2: Final Compound

(105) 1.24 g (0.002 mol) intermediate 8 a) were suspended in 20 ml water and stirred at 20 C. Around 20 ml of an ammonia solution in dioxane (30%) were added. The product mixture was heated to 75 C. for four hours. Then, the red suspension was cooled down to 20 C. and evaporated to dryness.

(106) Yield: 1.23 g, red, sticky solid, contained sodium bromide.

Example 9: 2-((4-(bis(2-ammonioethyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

Synthesis Scheme of Example 9

(107) ##STR00050##

(108) ##STR00051##

a) Step 1: 2((4-fluorophenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium iodide

(109) ##STR00052##
I)

(110) Monomethylation: A mixture of 300 g (1.58 mol) 2-((4-fluorphenyl)diazenyl)-1H-imidazole, 63 g (1.58 mol) sodium hydroxide pellets in 660 ml of a mixture of THF/water (600 ml/60 ml) was prepared under stirring. The reaction mixture was cooled to 0 C. Then 244 g (1.58 mol) methyl iodide was added to the mixture dropwise, keeping the inner temperature below 0 C. The reaction mixture was warmed to 20 C. and continued to stir for another two hours after methyl iodide had been added completely. The reaction mixture was concentrated under reduced pressure to remove tetrahydrofuran. Then the residue was poured into 2 liters of ice water. This suspension was stirred for another 30 minutes. Then the solid was filtered off. The residue was washed with water (500 ml, twice; the wet crude product was dried in vacuum at 40 C. for 12 hours. The product was obtained as a brown solid (196 g, 60%) which was used for the next step directly without further purification.

(111) II)

(112) Bismethylation: 195 g (0.96 mol) of the 2-((4-fluorophenyl)diazenyl-1-methyl-1H-imidazole from I), were suspended in a mixture of 500 ml acetonitrile and 100 ml methanol in a 1000 ml three-necked bottle equipped with mechanical stirrer and thermometer. The reaction mixture was stirred at 20 C., and then 272 g (1.92 mol) methyliodide was added to the mixture dropwise within 1 hour. The reaction mixture was continued to stir for another 12 hours at 20 C. after methyl iodide had been added completely. The reaction mixture was poured into 1 l of ethyl acetate. This suspension was stirred for another 20 minutes. Then the solid was filtered and the filter residue was washed with ethyl acetate (250 ml, twice), the crude product was dried in vacuum at 40 C. The product was obtained as a brown solid (290 g, 76%) which was used for the next step directly without further purification.

(113) .sup.1H NMR (DMSO-d.sub.6): =4.10 (s; 6H, CH.sub.3), 7.55-7.61 (m; 2H, Aryl-H), 8.05 (s; 2H, Aryl-H), 8.21-8.24 (m; 2H, Aryl-H) ppm.

b) Step 2: 2-((4-(bis(2-(tert-butoxycarbonylamino)ethyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(114) ##STR00053##
I)

tert-butyl N-[2-[2-(tert-butoxycarbonylamino)ethylamino]ethyl]carbamate

(115) ##STR00054##

(116) 25 g (0.243 mol) N1-(2-aminoethyl)ethane 1,2-diamine and 34.4 g (0.343 mol) triethylamine were suspended in 300 ml THF. The reaction mixture was stirred at 0 C. under argon atmosphere, then a solution of 118.4 g (0.485 mol) (2-tert.-butoxycarbonyloximino)-2-phenylacetonitrile in 100 ml THF was added dropwise within two hours. After addition, the reaction mixture was warmed to 20 C. and stirred for another 12 hours. The reaction mixture was concentrated to remove the THF, and the residue was diluted with 500 ml of dichloromethane. The mixture was washed with 10% aqueous sodium hydroxide solution (100 ml, three times), 100 ml of water and 100 ml of brine. After washing, the organic phases were dried with anhydrous magnesium sulfate. Finally, the organic phases were evaporated to dryness to give 60 g (82%) of crude product as colorless oil. This crude product was used in the next step without purification.

(117) .sup.1H NMR (DMSO-d.sub.6): =1.44 (s; 18H, CH.sub.3), 2.72 (m; 4H, CH.sub.2), 3.20-3.22 (m; 4H, CH.sub.2), 5.04 (br, NH) ppm

(118) II)

(119) 72 g (0.208 mol) 2-((4-fluorophenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium iodide and 26.6 g (0.317 mol) sodium bicarbonate were suspended in a mixture of 425 ml acetone and 125 ml of water at 20 C. Then the reaction mixture was cooled to 0 C. and stirred for 30 minutes under a nitrogen atmosphere. A solution of 32 g (0.0213 mol) tert.-butyl 2,2-azanediylbis(ethane-2,1-diyl)dicarbamate prepared above in 100 ml acetone was added to the mixture slowly. The solution was warmed to 20 C. and continued to stir for another 12 hours. Then the reaction mixture was diluted with 300 ml of dichloromethane and poured into a separatory funnel and washed with water (100 ml, five times). The organic phase was dried and contrated to give a crude red solid. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (40:1).

(120) Yield: 42 g (63%), red solid.

(121) .sup.1H NMR (DMSO-d.sub.6): =1.36 (s; 18H, CH.sub.3), 3.17 (m; 4H, CH.sub.2), 3.5-3.6 (m; 4H, CH.sub.2), 3.97 (s; CH.sub.3), 7.04-7.09 (m, 4H, Aryl-H), 7.73 (s; 2H, Imidazoyl-H) ppm.

c) Step 3 (Final Step)

(122) 42 g (0.0668 mol) of tert-butyl N-[2-[2-(tertbutoxycarbonylamino)ethylamino]ethyl]carbamate were dissolved in 150 ml of methanol. The reaction mixture was stirred at 20 C. for three hours while HCl gas was bubbled into the reaction system. The reaction mixture was stirred at 20 C. for another 3 hours, then concentrated to give a red solid. The crude product was purified by reversed phase chromatography (C.sub.18 column) eluted with water/ethanol gradient (10010/1).

(123) Yield: 16 g (59%), red solid.

(124) .sup.1H NMR (D.sub.2O): =3.2-3.3 (m; 4H, CH.sub.2), 3.8 (s; 6H, CH.sub.3), 3.8-3.9 (m; 4H, CH.sub.2), 6.8 (m; 2H, Aryl-H), 7.3 (s; 2H, Imidazoyl-H), 7.64 (d; 2H, Aryl-H) ppm.

Example 10: 2-((4-(bis(3-ammoniopropyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(125) ##STR00055##

Synthesis Scheme of Example 10

(126) ##STR00056##

a) Step 1: 2-((4-(bis(2-(tert-butoxycarbonylaminopropyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(127) ##STR00057##

(128) 72 g (0.208 mol) 2-((4-fluorophenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium iodide prepared in example 9, step 2 and 26.6 g (0.317 mol) sodium bicarbonate were stirred in acetone/water (4:1) mixture. The reaction mixture was cooled to 0 C. and stirred at this temperature for 30 minutes under nitrogen atmosphere. A solution of 72.4 g (0.2184 mol) tert-butyl 3,3-azanediylbis(propane-3,1-diyl)dicarbamate (preparation s. example 3) in 200 ml acetone was added into the mixture slowly. The solution was warmed to 20 C. and continued to stir for another 12 hours. Then the reaction mixture was diluted with dichloromethane (300 ml), then the reaction mixture was poured into separatory funnel and washed with water (water 100 ml5). The organic phase was dried with magnesium sulfate. The organic layer was evaporated to give the crude red solid. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (40:1).

(129) Yield: 79.3 g (58%), red solid.

(130) MS: 550 (ESI+, MW-I).

b) Final Step

(131) 42 g (120 mmol) of intermediate from example 10, step 1 was dissolved in 250 ml methanol. The reaction mixture was stirred at 20 C. and HCl gas was bubbled through into the reaction system. The reaction mixture was stirred at 20 C. for another 3 hours. Afterwards, the solution was evaporated to dryness. The crude product was purified by reversed phase (C.sub.18 column) chromatography eluted with water/ethanol (10010/1) gradient. Yield: 32 g (51%) as red solid.

(132) .sup.1H-NMR (D.sub.2O): =1.95-2.00 (m; 4H, CH.sub.2); 2.97-3.02 (m; 4H, CH.sub.2); 3.54-3.59 (m; 4H, CH.sub.2); 3.87 (s; 6H, CH.sub.3); 6.84-6.87 (m; 2H, Aryl-H); 7.27 (s; 2H, Imidazoyl-H); 7.87-7.90 (m, 2H, Aryl-H) ppm.

(133) MS: 330 (ESI+).

Example 11: 2-((4-(bis(4-ammoniobutyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(134) ##STR00058##

Synthesis Scheme of Example 11

(135) ##STR00059##

a) Step 1: 2-((4-(bis(2-(tert-butoxycarbonylaminobutyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(136) ##STR00060##

(137) 84.8 g (245.12 mmol) 2-((4-fluorophenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium iodide and 31 g (367.68 mmol) sodium bicarbonate were suspended in 500 ml of acetone, 125 ml water were added. The reaction mixture was cooled to 0 C. and stirred for 30 minutes at this temperature. A solution of 44 g (122.56 mmol) tert-butyl N-[4-[4-(tertbutoxycarbonylamino)butylamino]butyl]carbamate [preparation: M. Bradley et al., Tetrahedron, 53 (51) 17317 (1997); R. Bergeron, Synthesis 9 (1981) 732; R. Bergeron, Synthesis 8 (1982) 689] in 100 ml acetone was added dropwise. The reaction solution was warmed to 20 C. and continued to stir for another 48 hours. Afterwards, the reaction mixture was diluted with 300 ml dichloromethane (300 ml), poured into a separatory funnel and washed with water. The organic phase was dried with magnesium sulfate and evaporated in vacuum to give the crude material. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (50:1). Yield: 42 g (51%), red solid.

b) Step 2 (Final Step)

(138) 42 g (61.31 mmol) intermediate from step 1 were dissolved in 150 ml methanol and stirred at 20 C. HCl gas was bubbled through into the reaction system. The reaction mixture was stirred at 20 C. for another 3 hours. The reaction solution was evaporated and the crude product was purified by reverse phase chromatography (C.sub.18 column) eluted with water/ethanol gradient (10010/1). Yield: 24.3 g (86%), red solid.

(139) .sup.1H NMR (D.sub.2O): =1.74, 3.03 and 3.60 (each s, br; 10H, CH.sub.2), 3.94 (s, 6H, CH.sub.3), 6.94, 7.33 and 7.94 (each m, 6H, Aryl-H) ppm.

Example 12: 2-((4-(bis(5-ammoniopentyl)amino)phenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium dichloride iodide

(140) ##STR00061##

Synthesis Scheme of Example 12

(141) ##STR00062##

a) Step 1: tert-butyl N-[4-[4-(tert-butoxycarbonylamino)butylamino]butyl]carbamate

(142) ##STR00063##

(143) 40 g (144.4 mmol) of N1-(5-aminopentyl)-N1-benzylpentane-1,5-diamine prepared according to literature [R. Poulin et al, Bioorg. Med. Chem. Lett. 13 (2003), 3267] and 43.7 g (432.7.4 mmol) N,N-triethylamine were suspended in 400 ml THF. The reaction mixture was cooled to 0 C. A solution of 64 g (293.6 mmol) di-tert-butyl dicarbonate in 100 ml THF was added to the mixture dropwise. Stirring was continued for another 12 hours at 20 C. Afterwards, the product mixture was poured into 1 l of water. The mixture was extracted with ethyl acetate (250 ml, three times). The organic layers were combined and dried with anhydrous magnesium sulfate. The dried organic phase was evaporated in vacuum. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (200:1). Yield: 55 g (79%), colorless solid. To a suspension of 55 g (115.3 mmol) tert-butyl 5,5-(benzylazanediyl)bis(pentane-5,1-diyl)dicarbamate in 300 ml methanol were added 6 g of palladium/charcoal. The suspension was degassed under vacuum and purged with hydrogen several times. The product mixture was stirred under H.sub.2 atmosphere at 20 C. for 12 hours. The obtained product suspension was filtered. The filtrate was evaporated to give 39 g crude product as colorless oil. This was treated with 300 ml petrol ether. Under stirring, the reaction mixture was heated to 50 C. for 2 hours until the crude product was completely dissolved. Then, the reaction mixture was cooled to 0 C. for 2 hours. A white precipitate crushed out. The precipitate was collected by filtration, washed with 100 ml petroleum ether and dried in high vacuum at 30 C. for 12 hours.

(144) Yield: 35 g (78%), white solid.

(145) .sup.1H-NMR (CDCl.sub.3): =1.35-1.37 (m; 4H); 1.44 (s; 18H); 1.52-1.57 (m; 4H); 2.48-2.49 (m; 4H); 2.63-2.68 (m; 4H); 4.62-4.63 (m; 2H) ppm; MS m/z: 387 (ESI+).

b) Step 2: tert-butyl N-[5-[N-[5-(tert-butoxycarbonylamino)pentyl]-4-[(E)-(1,3-dimethylimidazol-1-ium-2-yl)azo]anilino]pentyl]carbamate iodide

(146) ##STR00064##

(147) 60 g (174.0 mmol) 2-((4-fluorophenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium iodide and 22 g (264.5 mmol) sodium bicarbonate were suspended in a mixture of 400 ml acetone and 100 ml water. The reaction mixture was stirred at 0 C. for 30 min under N2 atmosphere. A solution of 35 g (88.2 mmol) tert-butyl N-[4-[4-(tert-butoxycarbonylamino)butylamino]butyl]carbamate from step 1 in 100 ml acetone was added into the mixture slowly. The solution was warmed to 20 C. and continued to stir for another 48 hours. The reaction mixture was diluted with 300 ml dichloromethane and poured into a separatory funnel. The organic layers were washed with water thoroughly. The organic phase was dried and evaporated in vacuum to give the crude red solid. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (50:1).

(148) Yield: 39 g (60%), red solid.

(149) .sup.1H-NMR (CDCl3): 1.45 (s, 18H, CH.sub.3); 1.51-1.59 (m, 5H, CH.sub.2); 1.73 (s, 7H, CH.sub.2); 3.12-3.16 (m, 4H, CH.sub.2); 3.46-3.50 (m, 4H, CH.sub.2); 4.13 (s, 6H, CH.sub.3); 4.65-4.67 (m, 2H) ppm. MS: 586 (ESI+).

c) Step 3: Final Step

(150) 50 g (70.1 mmol) tert-butyl N-[5-[N-[5-(tert-butoxycarbonylamino)pentyl]-4-[(E)-(1,3-dimethylimidazole-1-ium-2-yl)azo]anilino]pentyl]carbamate iodide from step 2 was dissolved in 250 ml methanol and stirred at 20 C. Then, HCl gas was bubbled through into the reaction system. The reaction mixture was stirred for another 3 hrs. The obtained solution was evaporated in vacuum. The crude product was purified by reverse phase chromatography (C18 column) eluted with water/ethanol gradient (10010/1).

(151) Yield: 21 g (51%), red solid.

(152) .sup.1H NMR (D.sub.2O): =1.43 (m, br; 4H, CH.sub.2), 1.68 (m, br; 8H, CH.sub.2), 3.00 (m, br; 4H, CH.sub.2), 3.42 (m, br; 4H, CH.sub.2), 3.78 (s; 6H, CH.sub.3), 6.70, 7.19 and 7.62 (each m; 6H, Aryl-H) ppm.

Example 13: N1-[4-[(E)-(1-methylpyridine-1-ium-2-yl)azo]phenyl]benzene-1,4-diamine chloride

(153) ##STR00065##

Synthesis Scheme Example 13

(154) ##STR00066##

a) Step 1: (E)-(4-methoxyphenyl)-(1-methylpyridin-1-ium-2-yl)diazene chloride

(155) ##STR00067##

(156) A mixture of 23.5 g (0.25 mol) 2-aminopyridine and 42.1 (0.275 mol) 4-nitroanisole in 500 ml toluene were reacted with 12.7 g sodium according to literature [E. Taylor, C. P. Tseng, J. B. Rampal, J. Org. Chem. 47 (1982) 552; K. Rck-Braun, S. Dietrich, S. Kempa, B. Priewisch, Science of Synthesis, 31 b (2007)1425]. Yield: 21 g (39%). 20 g (around 0.093 mol) of crude (E)-(4-methoxyphenyl)-(2-pyridyl)diazene was dissolved in 160 ml water. 61.2 g (46 ml, 0.485 mol) dimethylsulfate were added dropwise within 1 hour. Simultaneously, pH 9 was adjusted by the addition of aqueous sodium hydroxide (10%) solution. During the addition, temperature of the reaction mixture must be kept below 30 C. The product mixture was stirred at 20 C. for 12 hours, again a pH of 9 was adjusted with sodium hydroxide solution.

(157) To that production suspension, 50 g of solid sodium chloride and 30 g of potassium chloride were added. Afterwards, the reaction mixture was carefully evaporated in vacuum while the temperature was kept below 60 C. The residue was treated with 400 ml ethanol and stirred for 1 hour. The solution was filtrated and the ethanolic solution evaporated to 1/10 of the volume. The product was precipitated with 100 ml of diethyl ether. The precipitate was filtered-off and dried at 40 C. in vacuum. Yield: 9.6 g (39%), brownish solid.

b) Step 2 (Final Step)

(158) A solution of 1.25 g (5 mmol) (E)-(4-methoxyphenyl)-(1-methylpyridine-1-ium-2-yl)diazene was suspended in 25 ml 2-propanol. 0.75 g (7 mmol) p-phenylenediamine was added dropwise within 10 minutes. The obtained dark suspension was diluted with 8 ml methanol and stirred at 20 C. for 12 hours. Then, the product suspension was heated to 40 C. and stirred for another 3 hours. The dark-blue suspension was cooled to 10 C. The formed precipitate was collected by filtration, washed with 200 ml of 2-propanol and dried at 30 C. for 12 hours.

(159) Yield: 1.44 g (86%), blue solid.

(160) .sup.1H NMR (D.sub.2O): =4.20 (s; 6H, CH.sub.3), 6.6-7.0 (m; 6H, Aryl-H), 7.51 (m; 1H, Aryl-H), 7.71 (m; 2H, Aryl-H), 7.80, 8.18 and 8.37 (m; each 1H, Aryl-H) ppm.

Example 14: 3-[2-[(E)-[4-(4-aminoanilino)phenyl]azo]pyridine-1-ium-1-yl]propylammonium dibromide

(161) ##STR00068##

Synthesis Scheme for Example 14

(162) ##STR00069##

a) Step 1: 2-[p-Methoxyphenyl)azo]pyridine

(163) ##STR00070##

(164) 2-[p-Methoxyphenyl)azo]pyridine has been prepared by condensation of 5.5 g (0.059 mol) pyridine-2-amine with 9.94 g (0.065 mol) 4-nitroanisole using sodium according to literature [E. Taylor, C. P. Tseng, J. B. Rampal, J. Org. Chem. 47 (1982) 552; K. Ru{umlaut over (c)}k-Braun, S. Dietrich, S. Kempa, B. Priewisch, Science of Synthesis, 31b (2007)1425].

(165) Yield: 5.2 g (41%) dark oil.

b) Step 2: 3-[2-[(E)-[4-(4-aminoanilino)phenyl]azo]pyridin-1-ium-1-yl]propylammonium dibromide

(166) ##STR00071##

(167) The reaction was performed under nitrogen. 1.2 g (0.006 mol) 2-[p-Methoxyphenyl)azo]pyridine were dissolved in 60 ml of acetonitrile. To the dark orange solution, 2.99 g (0.014 mol) 3-bromopropylamine hydrobromide were added. The reaction mixture was heated to 80 C. and kept at that temperature for 48 hours. During the heating period, a brown sticky precipitate was formed. The reaction mixture was cooled to 20 C. and the supernatant liquid was decanted. The solid residue was dissolved in methanol and the organic solution is evaporated.

(168) Yield: 2.0 g (81%), red solid.

(169) .sup.1H NMR (CD.sub.3OD): =2.49, 3.20 and 5.25 (m; each 2H, CH.sub.2), 4.04 (s; 3H, OCH.sub.3), 7.27 (m; 2H, Aryl-H), 8.16 (m; 1H, Aryl-H), 8.29 (m; 2H, Aryl-H), 8.37, 8.72 and 9.21 (m; each 1H, Aryl-H) ppm.

c) Step 3: Final Step

(170) The reaction is performed under nitrogen. 2.5 g (0.006 mol) 3-[2-[(E)-(4-methoxyphenyl)azo]pyridine-1-ium-1-yl]propylammonium dibromide were dissolved in 50 ml of methanol and stirred 20 C. Then, 0.8 g (0.007 mol) p-phenylendiamine was added. The reaction mixture has been stirred for 3 hours at 20 C. Afterwards, a mixture of 300 ml of isopropanol and 600 ml of ethyl acetate were poured into the reaction mixture. Within 30 minutes, the product precitated. The residue was filtered off, dissolved in methanol and evaporated to dryness.

(171) Yield: 0.4 g (13%), dark-violet solid.

(172) .sup.1H NMR (CD.sub.3OD): =2.42, 3.18 and 5.03 (m; each 2H, CH.sub.2), 6.81, 6.92, 7.12, 7.72, 8.05, 8.23, 8.38, 8.81 (m; totally 12H, Aryl-H) ppm.

(173) UV: .sub.max=569 nm.

Example 15: 2-((4-(bis(3-ammoniopropyl)amino)phenyl)diazenyl)-3-methyl 1,3-thiazole-3-ium trichloride

(174) ##STR00072##

Synthesis Scheme of Example 15

(175) ##STR00073##

a) Step 1: 2,2-(((4-(1,3-thiazol-2-yldiazenyl)phenyl)imino)di-3,1-propanediyl-bis(1H-isoindol-1,3(2H)-dione

(176) ##STR00074##
I)

2,2-(iminodi-3,1-propanediyl)bis(1H-isoindol-1,3(2H)-dione

(177) ##STR00075##

(178) 5 g (0.024 mol) N,N-bis(3-aminopropyl)aniline prepared according to literature [Arbusov et al. Doklady Ademii Nauk SSR, 91 (1953) 269] and 16 g (0.073 mol) ethyl 1,3-dioxoisoindolin-2-carboxylate were suspended in 100 ml chloroform and stirred at 20 C. Afterwards, the reaction mixture was heated to 70 C. and kept at this temperature for 12 hours. The solution was concentrated to dryness to give crude product as brown oil which was purified by recrystallization using methanol. Yield: 10.6 g (89%), white solid.

(179) Yield: 10.6 g (89%), white solid.

(180) II)

(181) Diazotization/Coupling: A mixture of 12.5 g (0.125 mol) thiazol-2-amine, 20 ml acetic acid (20 ml), 40 ml concentrated hydrochloric acid and 40 ml water was stirred at 20 C. The reaction mixture was cooled to 0 C. and stirred at this temperature for 30 min under nitrogen atmosphere. 9.3 g (0.134 mol) sodium nitrite solution in 40 ml water was added into the mixture slowly while keeping the inner temperature below 5 C. The solution was continued to stir at 5-0 C. for another 30 minutes. Then, a solution of 45 g (0.096 mol) 2-formyl-N-[3-[3-[(2-formylbenzoyl)amino]propylamino]propyl]benzamide from I) in 100 ml THF was added slowly while keeping the inner temperature between 0 and 5 C. The solution was stirred at 0 C. for another 30 minutes. The reaction mixture was warmed to 20 C., diluted with water (1000 ml) and neutralized with 2M sodium hydroxide solution. The reaction mixture was poured into a separatory funnel and extracted with 500 ml dichloromethane. The organic phase were combined, dried with magnesium sulfate and evaporated to dryness. The crude product was purified by silica gel chromatography eluted with dichloromethane/ethyl acetate (20:1). Yield: 36 g (65%), red solid.

b) Step 2: tert-butyl N-[3-[N-[3-(tert-butoxycarbonylamino)propyl]-4-[(E)-thiazol-2-ylazo]anilino]propyl]carbamate

(182) ##STR00076##

(183) A mixture of 30 g (0.052 mol) intermediate 15 a) was stirred in 600 ml of a mixture of dichloromethane/methanol (1:1). Then 30.5 g (0.52 mol) hydrazine hydrate was added dropwise under argon. After addition, the reaction mixture was stirred at 20 C. for another 12 hours. The reaction mixture was filtered and the filtrate was concentrated to give crude product. This crude product was dissolved in 300 ml of a mixture of dichloromethane/methanol (1:1) and stirred at 20 C. A solution of 283.4 g (1.3 mol) ditert-butyl dicarbonate in 300 ml dichloromethane was added dropwise under argon. After addition, the reaction mixture was stirred at 20 C. for another 12 hours. Then, the solution was evaporated to dryness. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (40:1). Yield: 11.6 g (42%), red solid.

c) Step 3: tert-butyl N-[3-[N-[3-(tert-butoxycarbonylamino)propyl]-4-[(E)-(3-methylthiazole-3-ium-2-yl)azo]anilino]propyl]carbamate chloride

(184) ##STR00077##

(185) A reaction mixture of 18 g (34.75 mmol) intermediate from step 2 and 18 g (130 mmol) potassium carbonate in 180 ml acetonitrile was stirred at 20 C. 49.3 g (347 mmol) methyliodide was added dropwise. The reaction mixture was heated to 50 C. and kept for 12 hours at this temperature under nitrogen atmosphere. The reaction mixture was filtered and the filtrate evaporated to dryness. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol (50:1). Yield: 13.8 g (75%), blue solid.

d) Step 4 (Final Step)

(186) 19 g (35.6 mmol) intermediate from step 3 was dissolved in 100 ml methanol and stirred at 20 C. Then, HCl gas was bubbled through into the reaction system. The reaction mixture was stirred at 20 C. for another 3 hours. The solution was evaporated to dryness in vacuum. The obtained crude product was purified by reversed phase chromatography (C.sub.18 column) eluted with water/ethanol gradient (10010/1).

(187) Yield: 11.7 g (81%), blue solid.

(188) .sup.1H NMR (D.sub.2O): =2.09 (s, br; 4H, CH.sub.2), 3.15 (s, br; 4H, CH.sub.2), 3.68 (m; 4H, CH.sub.2), 3.88 (s; 3H, CH.sub.3), 6.83 (s, br; Aryl-H), 7.42 (d; 2H, Aryl-H), 7.65 (s, br; 2H, Aryl-H) ppm.

Example 16: 1-(3-aminopropyl)-4-((E)-(4-(dimethylamino)phenyl)diazenyl)pyridinium bromide

(189) ##STR00078##

Scheme Example 16

(190) ##STR00079##

a) Step 1: N,N-Dimethyl-4-[(E)-pyridin-1-ium-4-ylazo]aniline bromide

(191) ##STR00080##

(192) This compound has been prepared according to a slightly modified literature procedure [S. Yitzchaik et al., J. Am. Chem. Soc. 2008, 130 (12) 4158].

(193) a) Diazotization: To a stirred mixture of 20 ml phosphoric acid (65%) and 10 ml nitric acid at 20 C., 4.0 g (0.043 mol) 4-amino-pyridine were added. The formed colorless solution was cooled down to a temperature range of 0-5 C. Within 30 minutes, 3.0 g (0.043 mol) of solid sodium nitrite were added portionwise. The reaction mixture was stirred for 20 minutes at 0-5 C., then 50 g of ice were given into the solution.

(194) b) Coupling: 3.2 g (0.026 mol) N,N-dimethylaniline were dissolved in 40 ml of phosphoric acid (65%). The formed yellowish solution was cooled down to a temperature range of 0-5 C. To that solution, the fresh diazo solution prepared in a) was added dropwise within 5 minutes. The formed orange reaction mixture was stirred for 4 hours at 0-5 C. Then no diazo could be detected (test with H-acid). The reaction mixture was warmed-up to 20 C. and further stirred for twelve hours.

(195) Work-up: The orange suspension was adjusted to pH 8.2 with 91.7 ml of 30% sodium hydroxide solution. The precipitate was filtered off and washed with 1000 ml of water. It was suspended in 1000 ml of water, stirred for 30 minutes and filtered off again. The moist residue was dissolved in 200 ml of methanol, heated to 60 C. and evaporated until recrystallization started. Then the reaction mixture is cooled down to 0 C., stirred at that temperature for 1 hour. The formed precipitate is filtered off and dried in high vacuum at 40 C.

(196) Yield: 1.63 g (27%) orange powder. .sub.max=540 nm.

b) Final Step

(197) 0.5 g (0.0022 mol) N,N-Dimethyl-4-[(E)-pyridin-1-ium-4-ylazo]aniline bromide prepared in example 11a) was dissolved in 20 ml of acetonitrile. To that reddish orange solution, 0.6 g (0.0026 mol) of 3-bromopropylamine hydrobromide was added. The reaction mixture was heated to 80 C. and kept at that temperature for 12 hours. Another 0.6 g (0.0026 mol) of bromopropylamine hydrobromide were added. The reaction mixture was stirred for another 12 hours. The formed red-violet precipitate was filtered off, washed with little cold acetonitrile and 100 ml of ethyl acetate and dried in high vacuum at 30 C. Yield: 910 mg dark green powder, contains unreacted 3-brompropylamine hydrobromide.

(198) .sup.1H NMR (D.sub.2O): =2.3 (m; 4H, CH.sub.2), 3.12 (m; 4H, CH.sub.2), 3.24 (s; 6H, CH.sub.3), 4.53 (m; 4H, CH.sub.2), 6.96 (m; 2H, Aryl-H), 7.9-8.0 (m; 4H, Aryl-H), 8.59 (m; 2H, Aryl-H) ppm.

(199) UV .sub.max=572 nm, MS (ESI): m/z=284 (C.sub.16H.sub.22N.sub.5Br).sup.+.

Example 17: 1-(4-aminobutyl)-4-((E)-(methyl(phenyl)hydrazono)methyl)pyridinium bromide

(200) ##STR00081##

Synthesis Scheme Example 17

(201) ##STR00082##

a) Step 1: N-methyl-N-[(E)-4-pyridylmethyleneamino]aniline

(202) ##STR00083##

(203) 25.5 g (238 mmol) N-methyl-phenylhydrazine and 24.8 g (202 mmol) 4-pyridinealdehyde were reacted according to the procedure given in WO2007025889. Yield: 36.4 g (85%).

b) Step 2: 1-(4-brombutyl)-4-((E)-(methyl(phenyl)hydrazono)methyl)pyridinium bromide

(204) ##STR00084##

(205) 2.11 g (0.010 mol) of N-methyl-N-[(E)-4-pyridylmethyleneamino]aniline prepared in step 1 and 10.8 g (0.05 mol) 1,4-dibrombutane were suspended in 50 ml of acetonitrile and stirred for 15 minutes at 20 C. The reaction mixture was heated to 85 C. and kept at this temperature for 12 hours. Afterwards, the reaction mixture was evaporated in vacuum to dryness. The sticky orange residue was suspended in 100 ml of acetone, heated to 50 C. for some minutes and cooled down to 20 C. The solution was evaporated to of the original volume followed by the addition of 50 ml 2-propanol. A precipitate was formed which was filtered off and dried in high vacuum at 40 C.

(206) Yield: 2.4 g (56%), orange sticky solid.

c) Final Step

(207) 2.1 g (0.010 mol) of 1-(4-brombutyl)-4-((E)(methyl(phenyl)hydrazono)methyl)pyridinium bromide were suspended in a mixture of 60 ml water/dioxane (1:1) and stirred for 15 minutes at 20 C. To that yellow solution, 10 ml of 30% aqueous ammonia solution was added. The reaction mixture was heated up to 75 C. and kept at that temperature for three hours. Afterwards, the yellow solution was evaporated in vacuum to of the original volume, at the same time the product crushed out.

(208) Yield: 2.2 g (62%), dark orange solid.

(209) .sup.1H NMR (DMSO-d.sub.6): =1.58, 1.98, 2.87, 4.52 (m; each 2H, CH.sub.2), 3.61 (s; 6H, CH.sub.3), 7.12, 7.43, 7.60, 7.85 8.21, 8.90 (each m; 10H, Aryl-H and CHN) ppm.

Example 18: N1-[4-[(E)-(1,3-dimethylimidazol-1-ium-2-yl)azo]phenyl]propane-1,2-diamine chloride

(210) ##STR00085##

Synthesis Scheme of Example 18

(211) ##STR00086##

(212) 6.7 g (7.8 ml, 90 mmol) of 1,2-diminopropane were suspended in 30 ml methanol. The stirred solution was heated to 60-65 C. At this temperature, a solution of 8.0 g (30 mmol) (E)-(1,3-dimethylimidazol-1-ium-2-yl)-(4-methoxyphenyl)diazene chloride prepared according to literature [WO2012150549, WO200909121] in 30 ml methanol was added dropwise within four hours. The product suspension were kept at 60-65 C. for 12 hours and then cooled to 20 C. The reaction mixture was evaporated in vacuum. The residue was dissolved in 100 ml of distilled water and 10 ml of potassium chloride solution (3M) were added. The solution was filtrated and evaporated to dryness in vacuum. The raw product was treated with 100 ml of methanol and the solution stored at 0 C. for 12 hours. Then, the formed precipitate was collected by filtration. Yield: 2.2 g (24%), red solid. The product was obtained as isomeric mixture.

Example 19: N-[4-[(E)-(1,3-dimethylimidazole-1-ium-2-yl)azo]phenyl]butane-1,4-diamine chloride

(213) ##STR00087##

Synthesis Scheme of Example 19

(214) ##STR00088##

(215) 40.0 g (0.15 mol) of 2((4-methoxyphenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium chloride [preparation s. WO2009090125] were dissolved in 50 ml ethanol. Under stirring at 20 C., 75 g (0.85 mol) 1,4-diaminobutane were added. The reaction solution was heated to 45 C. and kept at this temperature for 2 hours. The product mixture was diluted with 50 ml of ethanol and filtrated. The mother liquor was evaporated to of original volume. To that solution, 500 ml of methyl tert.butylether were added. The precipitate was collected by filtration and dried in high vacuum at 60 C. Yield: 38.7 g (80%), red solid.

Example 20: 1-amino-3-[4-[(E)-(1,3-dimethylimidazol-1-ium-2-yl)azo]anilino]propan-2-ol chloride

(216) ##STR00089##

Synthesis Scheme of Example 20

(217) ##STR00090##

(218) Under stirring, 34.6 g (0.1298 mol) 2((4-methoxyphenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium chloride were suspended in 80 g ethanol. The mixture was heated to reflux and filtrated hot. The mother liquor was cooled to 20 C. Under stirring, 28.41 g (0.2995 mol) 1,3-diamino-2-propanol was added. The mixture was heated to 55 C. for 10 hours. The formed precipitate was removed by filtration. The mother liquor was evaporated in vacuum until dryness. The raw product was treated with 150 ml methanol and heated to reflux. To that hot mixture, 300 g isopropanol was added. The formed precipitate was collected by filtration.

(219) Yield: 15.1 g (38%), red solid.

Example 21: N-[2-[4-[(E)-(1,3-dimethylimidazol-1-ium-2-yl)azo]anilino]ethyl]ethane-1,2-diamine chloride

(220) ##STR00091##

Synthesis Scheme of Example 21

(221) ##STR00092##

(222) 66.5 g (0.25 mol) 2((4-methoxyphenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium chloride were suspended in 300 ml ethanol. The mixture was heated to reflux and filtrated hot. The mother liquor was stirred at 55 C. At this temperature 26.03 g (0.25 mol) diethylenetriamine were added in portions within one hour. The product mixture was kept at 55 C. for 10 hours. The formed precipitate was removed by filtration. The mother liquor was evaporated in vacuum to dryness. The raw product was recrystallized in 400 ml of isopropanol. Yield: 9 g (11%), red solid. The product is a mixture of two isomers.

Example 22: N-[4-[(E)-(1,3-dimethylimidazol-1-ium-2-yl)azo]phenyl]-N,N-diethylpropane-1,3-diamine chloride

(223) ##STR00093##

Synthesis Scheme of Example 22

(224) ##STR00094##

(225) A mixture of 50 g (0.187 mol)) 2((4-methoxyphenyl)diazenyl)-1,3-dimethyl-1H-imidazol-3-ium chloride and 31.5 ml (26 g, 0.2 mol) N,N-diethyl-1,3-diaminopropane in 250 ml ethanol were treated, reacted and worked-up as described in example 21.

(226) Yield: 35 g (57%), red solid.

Example 23: (E)-1-(4-aminobutyl)-4-((2-(3-aminopropyl)-2-phenylhydrazono) methyl) pyridinium bromide

(227) ##STR00095##

Synthesis Scheme of Example 23

(228) ##STR00096##

a) Step 1: 2-[3-(N-[(E)-4-pyridylmethyleneamino]anilino)propyl]isoindoline-1,3-dione

(229) ##STR00097##

(230) 75 g (0.38 mmol) N-[(E)-4-pyridylmethyleneamino]aniline prepared according to WO2013046041 were suspended in 450 ml N,N-dimethylformamide and stirred at 20 C. under argon atmosphere. The reaction mixture was cooled down 30 C. 27.5 g (1.13 mol) sodium hydride was added slowly while keeping the reaction temperature below 25 C. A solution of 152 g (0.565 mol) N-(3-bromopropyl)phthalimide in 500 ml DMF was added into the mixture dropwise within one hour. Afterwards, the solution was warmed to 20 C. and continued to stir for another 12 hours. The reaction mixture was quenched by adding 100 ml water and poured into 1500 ml water. Stirring was continued for one hour. The obtained precipitate was collected by filtration, washed twice with 100 ml water and dried to give a yellow solid which was used for the next step directly without further purification.

(231) Yield: 74 g (63%).

(232) .sup.1H NMR (CDCl.sub.3): =2.11, 3.84 and 4.01 (m; each 2H, CH.sub.2), 6.98, 7.32, 7.46, 7.73, 7.85, 8.00 and 8.52 (m; totally 14H, Aryl-H and CHN) ppm.

(233) ESI-MS m/z 385.2 [M.sup.+].

b) Step 2: 2-[4-[4-[(E)-[3-(1,3-dioxoisoindolin-2-yl)propyl-phenyl-hydrazono]-methyl]pyridin-1-ium-1-yl]butyl]isoindoline-1,3-dione bromide

(234) ##STR00098##

(235) 74 g (0.193 mol) intermediate from step a) were suspended in 750 ml acetonitrile and stirred at 20 C. 114 g (0.405 mol) N-(4-brombutyl)phthalimide was added into the mixture. The product mixture was heated to reflux (85 C.) for another 24 hours. Afterwards, the reaction mixture was evaporated to dryness in vacuum. The crude product was purified by silica gel chromatography eluted with dichloromethane/methanol gradient (80:150:1).

(236) Yield: 74 g (69%), yellow solid.

(237) .sup.1H NMR (DMSO-d.sub.6): =2.04, 3.77, 4.25 and 4.91 (m; CH.sub.2), 7.10, 7.40, 7.57, 7.85, 8.19, 8.91 (m; Aryl-H and CHN) ppm.

c) Final Step

(238) 74 g (0.125 mol) intermediate from step b) were dissolved in 1200 ml ethanol and stirred at 20 C. under argon atmosphere. Within 20 minutes, 51 g (0.920 mol) hydrazine hydrate was added into the mixture dropwise. Subsequently, the reaction mixture was heated to 80 C. for 3 hours and afterwards concentrated to remove the solvent. When of solvent was removed, lots of white solid precipitated. This precipitate was filtered-off and washed with 50 ml ethanol twice. The organic phases were combined and concentrated to obtain a crude oil. The crude oil was stirred with 250 ml dichloromethane for 30 minutes. The formed precipitate was collected by filtration, washed twice with 50 ml dichloromethane and dried at 30 C.

(239) Yield: 27 g (60%).

(240) .sup.1H NMR (DMSO-d.sub.6): =1.44 (m; 2H, CH.sub.2), 1.85-1.97 (m; 4H, CH.sub.2), 2.77 (m; 4H, CH.sub.2), 4.23 (m; 2H, CH.sub.2), 4.53 (m; 2H, CH.sub.2), 7.13 (m; 1H, Aryl-H), 7.43 (d; 2H, Aryl-H), 7.62 (d; 2H, Aryl-H), 8.02 (m; 1H, CHN), 8.22 (d; 2H, Aryl-H), 8.87 (d; 2H, Aryl-H) ppm.

(241) ESI-MS m/z 326.2 [M.sup.+].

Example 24: N-[(E)-(1-hexylpyridin-1-ium-4-yl)methyleneamino]-N-phenyl-propane-1,3-diamine bromide

(242) ##STR00099##

Synthesis Scheme of Example 24

(243) ##STR00100##

a) Step 1: 2-[3-(N-[(E)-(1-hexylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione bromide

(244) ##STR00101##

(245) A suspension of 120 g (0.313 mol) 2-[3-(N-[(E)-4-pyridylmethyleneamino]anilino)propyl]isoindoline-1,3-dione prepared according to example 23, step 1 was stirred in 1000 ml acetonitrile at 20 C. 129 g (0.781 mol) 1-bromohexane was added into the mixture slowly. The reaction mixture was continued to stir for another 12 hours. Afterwards, the reaction mixture was concentrated to give the crude product which was purified by silica gel chromatography eluted with a dichloromethane/methanol mixture (50:1).

(246) Yield: 134 g (78%), yellow solid.

(247) .sup.1H NMR (DMSO-d.sub.6): =0.84 (m; Alkyl-H), 1.2-1.4 (m (br), CH.sub.2), 1.9-2.2 (m (br); CH.sub.2), 3.85, 4.13 and 4.76 (m, CH.sub.2), 7.1 (m; Aryl-H), 7.3-7.5 (m (br); Aryl-H), 7.7-7.9 (m (br); Aryl-H), 8.07 and 9.00 (Aryl-H and CHN) ppm.

(248) ESI-MS m/z 469.3 [M.sup.+].

b) Final Step

(249) A mixture of 100 g (0.181 mol) 2-[3-(N-[(E)-(1-hexylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione bromide in 1000 ml ethanol was treated with 48 g (0.914 mol) hydrazine hydrate. The reaction was done according to the procedure described in example 23, final step. The final purification by precipitation was done with toluene/tetrahydrofuran (5:1) mixture.

(250) Yield: 29 g (38%), yellow solid.

(251) .sup.1H NMR (DMSO-d.sub.6): =0.88 (m; 3H, CH.sub.3), 1.29 (m; 6H, CH.sub.2), 1.73-1.88 (m; 6H, CH.sub.2), 2.69 (m; 2H, CH.sub.2), 4.20 (m; 2H, CH.sub.2), 4.46 (m; 2H, CH.sub.2), 7.12 (m; 1H, Aryl-H), 7.41 (m; 2H, Aryl-H), 7.61 (m (br); 2H, Aryl-H), 7.93 (s; 1H, CHN), 8.16 (d; 2H, Aryl-H), 8.82 (d; 2H, Aryl-H) ppm.

(252) ESI-MS m/z 339.3 [M.sup.+].

Example 25: N-[(E)-(1-pentylpyridin-1-ium-4-yl)methyleneamino]-N-phenyl-propane-1,3-diamine bromide

(253) ##STR00102##

Synthesis Scheme of Example 25

(254) ##STR00103##

a) 2-[3-(N-[(E)-(1-pentylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione bromide

(255) ##STR00104##

(256) A mixture of 120 g (0.313 mol) 2-[3-(N-[(E)-4-pyridylmethyleneamino]anilino)propyl]-isoindoline-1,3-dione and 118 g (0.781 mol) 1-bromopentane in 1000 ml acetonitrile was treated, reacted and worked-up according to the procedure given in example 24, step 1.

(257) Yield: 138 g (80%), yellow solid.

(258) .sup.1H NMR (DMSO-d.sub.6): =0.87 (m; Alkyl-H), 1.2-1.4 (m (br), CH.sub.2), 1.9-2.2 (m (br); CH.sub.2), 3.85, 4.13 and 4.79 (m, CH.sub.2), 7.1 (m; Aryl-H), 7.3-7.5 (m (br); Aryl-H), 7.7-7.9 (m (br); Aryl-H), 8.1 and 9.05 (Aryl-H and CHN) ppm.

(259) ESI-MS m/z 455.2 [M.sup.+].

b) Final Step

(260) A mixture of 100 g (0.181 mol) 2-[3-(N-[(E)-(1-pentylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione bromide and 48 g (0.914 mol) hydrazine hydrate were treated, reacted and worked-up according to the procedure described in example 23, final step. The purification by precipitation was done with a toluene/tetrahydrofuran (5:1) mixture.

(261) Yield: 26 g (35%), yellow solid.

(262) .sup.1H NMR (DMSO-d.sub.6): =0.88 (m; 3H, CH.sub.3), 1.33 (m; 4H, CH.sub.2), 1.74 (m; 2H, CH.sub.2), 1.90 (m; 2H, CH.sub.2), 2.70 (m; 2H, CH.sub.2), 4.19 (m; 2H, CH.sub.2), 4.47 (m; 2H, CH.sub.2), 7.12 (m; 1H, Aryl-H), 7.42 (m; 2H, Aryl-H), 7.62 (m (br); 2H, Aryl-H), 7.94 (s; 1H, CHN), 8.17 (d; 2H, Aryl-H), 8.83 (d; 2H, Aryl-H) ppm.

(263) ESI-MS m/z 325.2 [M.sup.+].

Example 26: N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]-N-phenyl-propane-1,3-diamine iodide

(264) ##STR00105##

Synthesis Scheme of Example 26

(265) ##STR00106##

a) Step 1: 2-[3-(N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione iodide

(266) ##STR00107##

(267) A mixture of 120 g (0.313 mol) 2-[3-(N-[(E)-4-pyridylmethyleneamino]anilino)propyl]-isoindoline-1,3-dione and 111 g (0.781 mol) methyl iodide in 1000 ml acetonitrile was treated, reacted and worked-up according to the procedure given in example 24, step 1. Column chromatography was done with a dichloromethane/methanol mixture (50:1).

(268) Yield: 124 g (75%), yellow solid.

(269) .sup.1H NMR (DMSO-d.sub.6): =2.1 (m (br), CH.sub.2), 3.87 and 4.14 (m; CH.sub.2), 4.51 (s; CH.sub.3), 7.1 (m; Aryl-H), 7.2-7.4 (m (br); Aryl-H), 7.8-8.0 (m (br); Aryl-H), 8.06 and 8.90 (Aryl-H and CHN) ppm.

(270) ESI-MS m/z 399.2 [M.sup.+].

b) Final Step

(271) A reaction mixture of 86 g (0.183 mol) 2-[3-(N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]anilino)propyl]isoindoline-1,3-dione iodide and 48 g (0.914 mol) hydrazine hydrate was treated, reacted and worked-up according to the procedure described in example 23, final step. The purification by precipitation was done with toluene/tetrahydrofuran (5:1) mixture.

(272) Yield: 22 g (30%), yellow solid.

(273) .sup.1H NMR (DMSO-d.sub.6): =1.83 (m; 2H, CH.sub.2), 2.85 (m; 2H, CH.sub.2), 4.24 (m; 5H, CH.sub.3+CH.sub.2), 5.34 (d (br); 2H, CH.sub.2), 7.12 (m; 1H, Aryl-H), 7.44 (m; 2H, Aryl-H), 7.62 (m; 2H, Aryl-H), 7.95 (s; 1H, CHN), 8.16 (d; 2H, Aryl-H), 8.74 (d; 2H, Aryl-H) ppm.

(274) ESI-MS m/z 269.2 [M.sup.+].

Example 27: N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]-N-phenyl-pentane-1,5-diamine iodide

(275) ##STR00108##

Synthesis Scheme of Example 27

(276) ##STR00109##

a) Step 1: 2-[5-(N-[(E)-4-pyridylmethyleneamino]anilino)pentyl]isoindoline-1,3-dione

(277) ##STR00110##

(278) 60 g (0.302 mol) N-[(E)-4-pyridylmethyleneamino]aniline in 350 ml N,N-dimethylformamide were stirred at 20 C. under argon atmosphere. The reaction mixture was cooled down 30 C. 22 g (0.903 mol) sodium hydride was added slowly while keeping the reaction temperature below 25 C. Afterwards, a solution of 121 g (0.452 mol) N-(5-bromopentyl)phthalimide in 500 ml N,N-dimethylformamide was added into the mixture dropwise within one hour. After the addition, the product mixture was warmed to 20 C. and continued to stir for another 12 hours. Then, the reaction was quenched by adding 20 ml water. Another 600 ml water were poured into the reaction mixture. The formed precipitate was collected by filtration and washed with distilled water. The obtained crude product was used for the next step directly without further purification.

(279) Yield: 88 g (75%), yellow solid.

(280) ESI-MS m/z 412.2 [M.sup.+].

b) 2-[5-(N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]anilino)pentyl]isoindoline-1,3-dione iodide

(281) ##STR00111##

(282) 71 g (0.183 mol) crude 2-[5-(N-[(E)-4-pyridylmethyleneamino]anilino)pentyl]isoindoline-1,3-dione were suspended in 500 ml dichloromethane and stirred at 20 C. 54.5 g (0.384 mol) methyl iodide were added into the mixture slowly. The solution was continued to stir at 20 C. for another 12 hours. Afterwards, the reaction mixture was evaporated to dryness in vacuum. The crude product was purified by silica gel chromatography eluted with a dichloromethane/methanol gradient (50:120:1).

(283) Yield: 74 g (69%), yellow solid.

(284) .sup.1H NMR (DMSO-d.sub.6): =1.50, 1.67, 1.87 (m; CH.sub.2), 3.28 and 4.13 (m; CH.sub.2), 4.23 (s; CH.sub.3), 7.12 (m; Aryl-H), 7.42 (m; Aryl-H), 7.56 (m; Aryl-H), 7.88 (m; Aryl-H), 8.17 (m; Aryl-H), 8.4-8.6 (m (br); Aryl-H and CHN), 8.75 (m; Aryl-H) ppm.

c) Final Step

(285) 70 g (0.165 mol) 2-[5-(N-[(E)-(1-methylpyridin-1-ium-4-yl)methyleneamino]anilino)pentyl]isoindoline-1,3-dione iodide was dissolved in 1000 ml ethanol and stirred at 20 C. under argon atmosphere. 47 g (0.827 mol) hydrazine hydrate were added into the mixture dropwise within 20 minutes. The reaction mixture was heated to 80 C. and stirred at this temperature for three hours. Afterwards, the reaction mixture was cooled down to 20 C. The formed precipitate was collected and washed with ethanol. The combined organic phases were evaporated in vacuum to yield an oily raw product. This crude oil was taken up with 1000 ml of toluene/tetrahydrofuran mixture (5:1). Again, the formed precipitate was filtered-off and washed with the used toluene/tetrahydrofuran mixture. This crystallization was repeated twice.

(286) Yield: 21 g (55%), yellow solid.

(287) .sup.1H NMR (D.sub.2O): =1.45 (m; 4H, CH.sub.2), 1.68 (m; 2H, CH.sub.2), 2.95 (t; 2H, CH.sub.2), 3.71 (m; 2H, CH.sub.2), 3.96 (s; 3H, CH.sub.3), 6.81 (m; 1H, Aryl-H), 6.82 (m; 3H, Aryl-H+CHN), 7.25 (m; 2H, Aryl-H), 7.59 (m; 2H, Aryl-H), 8.10 (s; 2H, Aryl-H) ppm.

(288) ESI-MS m/z 297.2 [M.sup.+].

B. APPLICATION EXAMPLES

(289) A 0.5% solution of the dye adjusted to pH 10 with ammonia is mixed with the same weight of 6% hydrogen peroxide solution.

(290) This mixture is applied with a brush on two hair strands (Piedmont white hair from international Hair Importers). After 30 min. at room temperature the tresses are rinsed, shampooed, rinsed and dried.

(291) To determine the wash fastness one dyed tress is washed with a commercial shampoo using approx. 0.5 g shampoo for each tress under tap water (water temperature: 37 C.+/1 C.; flow rate 5-6 l/min). Finally the tress is rinsed under tap water, pressed out with a paper towel, combed and dried with a hair dryer or at room temperature. This procedure is repeated 24 times.

(292) The results are summarized in the following table:

(293) TABLE-US-00001 dE washing fastness Color 24 washed with shampoo Example Red 4.5 1 Red 9.3 2 Red 6.2 3 Red 2.7 4 Red 4.6 6 Red 3.6 7 Red 3.8 8 Blue 5.2 13 Violet 2.0 16 Yellow 2.8 17