The present invention relates to an improved method of synthesis of 1-methylamino-4-(N, N-dimethyl-N-propyl-3'-ammonium-n-propyl amino)-9, 10-anthraquinone bromide.

1 -methylamino-4- (N, N-dimethyl-N-propyl-3'-ammonium-n-propylamino) -9,10-anthraquinone bromide is commonly known as BQB and is represented by Formula VIII of the accompanying drawings.

BACKGROUND OF THE INVENTION:

Anthraquinones and their quaternary ammonium side chains are known in the art. These Anthraquinones are known to possess hair-dyeing properties (British patent 909700) and possess both, excellent solubility in water and good absorption capacity, without dyeing the skin to any considerable extent.

According to information obtained from Wikipaedia, Anthraquinone, also called anthracenedione or dioxoanthracene, is an aromatic organic compound with formula C14H802. Several isomers are possible, each of which can be viewed as a quinone derivative. The term anthraquinone, however, almost invariably refers to one specific isomer, 9, 10-anthraquinone (IUPAC: 9, 10-dioxoanthracene) wherein the keto groups are located on the central ring. It is a building block of many dyes and is used in bleaching pulp for papermaking. It is know to obtain 9, 10-Anthraquinone industrially by the oxidation of anthracene, a reaction that is localized at the central ring.

Chromium (VI) is the typical oxidant. It is also prepared by the Friedel-Crafts reaction of benzene and phthalic anhydride in presence of AICI3. The resulting o-benzoylbenzoic acid then undergoes cyclization, forming anthraquinone. This reaction is useful for producing substituted anthraquinones. The Diels-Alder reaction of naphthoquinone and butadiene followed by oxidative dehydrogenation will also produce 9,10-anthraquinone. Lastly, BASF has developed a process that proceeds via the acid-catalyzed dimerization of styrene to give a 1, 3-diphenylbutene, which then can be transformed to the anthaquinone.

It also arises via the Rickert-Alder reaction, a retro-Diels-Alder reaction shown below:-

In a classic (1905) organic reaction called the Bally-Scholl synthesis, named after Oscar Bally and Roland Scholl, anthraquinone condenses with glycerol forming benzanthrone. In this reaction, the quinone is first reduced with copper metal in sulfuric acid (converting one ketone group into a methylene group) after which the glycerol is added. (See enclosed reaction scheme 4)

Reaction Scheme 4

US patent no 3817698 discloses another anthraquinone dye formed by covalent bond between two dye stuffs (III).

British patent 1053535 discloses the dyestuff of the formula (IV).


US patent no 5314505 discloses aminoanthraquinone hair dyes possessing a quaternary center with a lengthy aliphatic chain. These dyes were found to have higher affinity to hair, are shampoo stable and result in an uniform dyeing of hair.

This literature points to the importance of anthraquinone compounds and the continued interest in their use as dyeing materials.

US patent 5891200 discloses novel anthraquinone side chain, which is useful as hair dyes and more particularly as semi permanent blue hair dyes. According to the present invention the lead candidate 1-methylamino-4-(N,N-dimethyl-N-propyl-3'-ammonium-n-propylamino)-9,10-anthraquinone bromide of Formula VIII was synthesized as shown in Scheme-1 of the accompanying drawings which is given below. Scheme-1

According to present invention there is provided an improved method of synthesis of 1-methylamino-4-(N, N-dimethyl-N-propyl-3'-ammonium-n-propyl amino)-9,10-anthraquinone bromide, (hereinafter known as BQB) which comprises:-

Preparing 1-methylamino-4 [[3-(N,N-methyl-n-propyl-(amino)propyl]amino]-9,10-athraquinone (X) by a method as herein described and thereafter preparing 1-methyl amino - (N,N-dimethyl-N-propyl-3'ammonium-n-propyl amino) -9,10-anthraquinone bromide (BQB) by a method as herein described and when desired Compound VIII was isolated in high yield by quaternising the compound X, with methyl bromide 1-methylamino-4 [[3-(N,N-methyl-n-propyl-(amino)propyl]amino]-9,10-athraquinone (X) is prepared as under:

To a stirred solution of 4-bromo-1 -methyl amino-9,10-anthraquinone (VI) in DMSO Cu2 acetate and sodium acetate was added sequentially, followed by N,N methyl-n-propyl amino propyl amine ,the reactants were heated to 70-75°C under N2 blanket for a period of 8-12 hrs [TLC], the reaction mixture was quenched in water at 90-100C, followed by IPA ,the contents were again heated to 65-95°C, followed by water addition & cooling to 35°C to yield (X) 1-methyl amino - (N,N-dimethyl-N-propyl-3'ammonium-n-propyl amino) -9,10-anthraquinone bromide (BQB) is prepared as under:

To a clean IL SS hydrogenator compound X NMP & tri butyl amine were added, the contents were heated under agitation (90-95°C) and methyl bromide bubbled under pressure, the reaction was continued for about 10-12 hrs and then cooled to 35-45°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 70-90°C followed by slow cooling to about 30°C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB.

The reaction was continued for about 10 hrs and then cooled to 40°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 80°C followed by slow cooling to about 30°C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB.

Contents were heated under agitation (90-95°C) and methyl bromide bubbled under pressure, the reaction was continued for about 10 hrs and then cooled to 40°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 80°C followed by slow cooling to about 30°C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB.

The above synthetic sequence results in higher content of impurity VII in the final product. Prolonged reaction times, and varied modifications of the reaction conditions in no case leads to the lowering of the impurity profile to less than 0.6%-1.0%.

DETAILED DESCRIPTION OF THE INVENTION:

The present invention is directed towards the synthesis of 1-methylamino-4- (N, N-dimethyl-N-propyl-3'-ammonium-n-propylamino)-9,10- anthraquinonebromide (BQB), leading to better reactive quarternisation and hence resulting in lower reaction times and avoidance of the impurity VII as shown in Scheme -2. Scheme - 2

A key intermediate n-methyl-n-propyl aminopropylamine (IX) was synthesized following literature procedures (JACS 1946, 68, 1911) (Scheme-3). An intermediate, 1-methyl amino-4-[[3-(N-methyl-N-propyl amino) propyl] amino]-9,10-anthraquinone (Compound X) could be obtained by reacting compound VI with an amine derivative N,N methyl-n-propyl amino propyl amine, IX. Suitable solvents employed for the above purpose are DMSO, DMF, NMP, DMSO being the most preferred solvent.

Finally, BQB (Compound VIII) was isolated in high yield by quaternising the compound X, with methyl bromide as shown in Scheme -3 Scheme - 3

We shall now describe the present invention with reference to the accompanying examples which are given by way of illustration but does not restrict the scope of present invention.

Example 1
[For preparation of 1-methylamino-4[[3-(N,N-methyl-n-propyl- (amino)propyl]amino]-9,10-athraquinone (X)]

To a stirred solution of 4-bromo-1-methyl amino-9,10-anthraquinone (VI) [100g, 0.316 moles) in DMSO (370 ml) Cu2 acetate (0.0059 g) and sodium acetate (51.2 g, 0.624 moles) was added sequentially, followed by N,N methyl-n-propyl amino propyl amine (115.08). The flask was heated to 70-75°C under N2 blanket for a period of 10 hrs [TLC] and a intensely blue color transformation was noticed. The reaction mixture was quenched in water (800 ml) at 90-100°C, followed by IPA (120 ml). The contents were again heated to 75°C, followed by water addition (120 ml) & cooling to 35°C to yield (X) [120 g, 95%].

Example 2

[For preparation of 1-methyl amino - (N,N-dimethyl-N-propyl-3'ammonium-n- propyl amino) -9,10-anthraquinone bromide (BQB) ]

To a clean IL SS hydrogenator compound X (100, 0.297 moles) NMP (335 ml) & tri butyl amine 14 ml & were sequentially added. The contents were heated under agitation (90-95°C) and methyl bromide bubbled under pressure (2-2.5 Kg/Cm2). The reaction was continued for about 10 hrs and then cooled to 40°C, followed by pressure release.

IPA (Isopropyl alcohol, 230 ml) was then slowly added & the contents heated to 80C followed by slow cooling to about 30°C. The thick reaction contents were further cooled to 5°C, filtered & washed with chilled IPA (200 ml). The crude quaternary salt was recrystallized from n-butanol & water (790:10 ml) to yield the pure sample of BQB (85.0 g).

WE CLAIM:

1. An improved method of synthesis of 1-methylamino-4-(N, N-dimethyl-N-propyl-3'-ammonium-n-propyl amino)-9, 10-anthraquinone bromide,(hereinafter known as BQB) which comprises:Preparing 1-methylamino-4[[3-(N,N-methyl-n-propyl-(amino)propyl]amino]-9,10-athraquinone (X) by a method as herein described and thereafter preparing 1-methyl amino - (N,N-dimethyl-N-propyl- 3'ammonium-n-propyl amino) -9,10-anthraquinone bromide (BQB) by a method as herein described and when desired Compound VIII was isolated in high yield by quaternising the compound X, with methyl bromide

2. Process as claimed in claim 1 wherein 1-methylamino-4[[3-(N,N- methyl-n-propyl-(amino)propyl]amino]-9,10-athraquinone (X) is prepared as under:

to a stirred solution of 4-bromo-1-methyl amino-9,10-anthraquinone (VI) in DMSO Cu2 acetate and sodium acetate was added sequentially, followed by N,N methyl-n-propyl amino propyl amine ,the reactants were heated to 70-75°C under N2 blanket for a period of 8-12 hrs [TLC], the reaction mixture was quenched in water at 90-100°C, followed by IPA ,the contents were again heated to 65-95°C, followed by water addition & cooling to 35C to yield (X)

Process as claimed in claim 1 and 2 wherein finally 1-methyl amino -(N,N-dimethyl-N-propyl-3'ammonium-n-propyl amino) -9,10- anthraquinone bromide (BQB) is prepared as under : to a clean IL SS hydrogenator compound X NMP & tri butyl amine were added, the contents were heated under agitation (90-95°C) and methyl bromide bubbled under pressure, the reaction was continued for about 10-12 hrs and then cooled to 35-45°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 70-90°C followed by slow cooling to about 30°C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB

3. Process as claimed in claim 2 wherein the reaction was continued for about 10 hrs and then cooled to 40°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 80°C followed by slow cooling to about 30°C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB

4. Process as claimed in claim 3 wherein contents were heated under agitation (90-95°C) and methyl bromide bubbled under pressure, the reaction was continued for about 10 hrs and then cooled to 40°C, followed by pressure release, IPA (Isopropyl alcohol) was then slowly added & the contents heated to 80C followed by slow cooling to about 30C, the thick reaction contents were further cooled, filtered & washed with chilled IPA, the crude quaternary salt was recrystallized from n-butanol and water to yield the pure sample of BQB

5. Process as claimed in claim 1 wherein Compound VIII was isolated in high yield by quaternising the compound X, with methyl bromide and particularly as shown in Scheme 3.