Process for the preparation of indigo carmine

Abstract

The present invention relates to an improved process for preparation of Indigo carmine of Formula (I), in high purity, more than 99.5%.

Claims

1. An improved process for the preparation of Indigo carmine of formula (I) having a purity of 99.5%, ##STR00016## the process comprising: a) treating an Indole of compound formula (II) ##STR00017## with peroxide in the presence of a catalyst in an alcoholic solvent to give an indigo of compound formula (III) ##STR00018## b) reacting the Indigo of compound formula (III) ##STR00019## with sulfuric acid and adding an organic solvent then washing or purifying in an ester solvent to produce an indigodisulfonic acid of compound formula (IV) ##STR00020## and c) reacting indigodisulfonic acid of formula (IV) ##STR00021## in an aqueous media with a sodium source compound and washing with a nitrile or a ketonic solvent to give the Indigo carmine of formula (I).

2. The process according to claim 1, wherein in step (a) the reaction carried is out in an alcohol solvent selected from group methanol, ethanol, isopropanol, n-butanol, and tert-butanol.

3. The process according to claim 1, wherein in step (a) the reaction is carried out in a peroxide compound selected from hydrogen peroxide and cumene hydrogen peroxide in cumene.

4. The process according to claim 1, wherein in step (a) the reaction is carried out at a temperature ranging from 80 C. to 120 C.

5. The process according to claim 1, wherein in step (a) the reaction is carried out in the presence of a catalyst, which is Molybledenumhexacarbonyl (Mo(CO).sub.6).

6. The process according to claim 1, wherein in step (b) the reaction is carried out at a temperature ranging from 50 C. to 90 C.

7. The process according to claim 1, wherein in step (b) the reaction is carried out in a solvent, which is an organic solvent.

8. The process according to claim 1, wherein in step (b) the washing or purifying is carried out in the ester solvent, which is selected from methyl acetate and ethyl acetate.

9. The process according to claim 1, wherein the aqueous media is only water.

10. The process according to claim 1, wherein in step (c) the reaction is carried out at a temperature ranging from 20 C. to 40 C.

11. The process according to claim 1, wherein in step (c) the sodium source compound is selected from sodium metal, sodium hydride, and sodium hydroxide.

12. The process according to claim 11, wherein in step (c) the washing is carried out in a solvent selected from acetone and acetonitrile.

13. The process according to claim 2, wherein in step (a) the alcohol solvent is tert-butanol.

14. The process according to claim 3, wherein in step (a) the reaction is carried out in cumene hydrogen peroxide in cumene.

15. The process according to claim 4, wherein in step (a) the reaction is carried out at a temperature ranging from 95 C. to 100 C.

16. The process according to claim 6, wherein in step (b) the reaction is carried out at a temperature ranging from 75 C. to 85 C.

17. The process according to claim 7, wherein in step (b) the reaction is carried out in acetic acid.

18. The process according to claim 8, wherein in step (b) the ester solvent is ethyl acetate.

19. The process according to claim 10, wherein in step the reaction is carried out at a temperature ranging from 25 C. to 30 C.

20. The process according to claim 12, wherein in step the washing is carried out in acetone.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1: A crystalline form of Indigodisulfonic acid of formula (IV) having obtain by example 2.

(2) FIG. 2: A crystalline form of Indigodisulfonic acid of formula (IV) having obtain by example 3.

DETAILED DESCRIPTION OF THE INVENTION

(3) A first object of the present invention to provide an improved process for the preparation of Indigo carmine of Formula (I) having grater than 99.5%,

(4) ##STR00007##

(5) Thus, condensation indigodisulfonic acid of compound formula (IV)

(6) ##STR00008##
using aqueous media in sodium source of compound and wash with ketonic solvent to give title compound formula (I).

(7) Another embodiment of present invention process carried out in aqueous media as water, and sodium source, here sodium source define as sodium metal, sodium hydroxide, sodium acetate, but preferably salt is sodium hydroxide.

(8) Another embodiment of the present invention reaction is carried out at temperature range about 15 C. to 40 C., but preferably temperature is 25 C. to 30 C.

(9) Another embodiment of invention is product wash with in ketonic solvent and nitrile as solvent, ketonic and nitrile solvent define as acetone, Acetonitrile but preferably solvent is acetone.

(10) The crude compound purification reaction is usually run in a suitable nitrile and ketonic solvent such as water or a mixture of water and a ketonic and nitrile solvent such as acetone, Acetonitrile but preferably solvent is acetone and water.

(11) Present invention provides isolation of compound formula (IV)

(12) ##STR00009##

(13) Another embodiment of the present invention making compound formula (IV) having HPLC purity achieved 99.0%.

(14) A crystalline form of Indigodisulfonic acid of Formula (IV) characterized by X-ray powder diffraction (XRPD) pattern having peaks at 2 theta value 14.04, 17.15, 23.61 and 27.152 C., FIG. 1: XRPD pattern of powder diffractogram of Indigodisulfonic acid of Formula (IV)

(15) A crystalline form of Indigodisulfonic acid of Formula (IV) characterized by X-ray powder diffraction (XRPD) pattern having peaks at 2 theta value 12.76, 17.08, 17.95, 18.32, 20.31, 25.86 and 27.232 C., FIG. 2: XRPD pattern of powder diffractogram of Indigodisulfonic acid of Formula (IV)

(16) Process for making indigodisulfonic acid of compound formula (IV) comprising Indole of compound formula (II)

(17) ##STR00010##
treating with peroxide in presence of catalyst in alcoholic solvent to give indigo of compound formula (III)

(18) ##STR00011##

(19) Indigo of compound formula (III)

(20) ##STR00012##
react with sulfuric acid and adding organic solvent then wash or purification in ester solvent to given to indigodisulfonic acid of compound formula (IV).

(21) ##STR00013##

(22) Another embodiment of invention making indigo of compound formula (III) is reaction carried out in alcoholic solvent, solvent define as methanol, ethanol, isopropanol, n-butanol, tert-butanol but preferably solvent is tert-butanol.

(23) Another embodiment of invention making indigo of compound formula (III) is reaction carried out in peroxide, the reaction carried out in peroxide compound is define as hydrogen peroxide, cumene hydrogen peroxide in cumene preferably cumene hydrogen peroxide in cumene.

(24) Another embodiment of invention making indigo of compound formula (III) is reaction carried out in presence of catalyst is call Molybledenumhexacarbonyl Mo(CO).sub.6. Catalyst using less amount of 0.00085 mole.

(25) Another embodiment of the present invention making indigo of compound formula (III) reaction is carried out at temperature range about 75 C. to 120 C., but preferably temperature is 80 C. to 85 C.

(26) Another embodiment of the present invention process according to step-(b) using the compound formula (V)

(27) ##STR00014##

(28) Indigo of compound formula (III)

(29) ##STR00015##
react with sulfuric acid and adding organic solvent then wash or purification in ester solvent to given to indigodisulfonic acid of compound formula (IV).

(30) Another embodiment of the present invention making compound formula (IV) reaction is carried out in organic acid, acetic acid, isopropyl acetate but preferable acetic acid.

(31) Another embodiment of invention making compound formula (IV) is wash/purification carried out in ester solvent, solvent define as ethyl acetate, isopropyl acetate but preferably solvent is ethyl acetate.

(32) Another embodiment of the present invention reaction is carried out at temperature range about 75 C. to 90 C., but preferably temperature is 80 C. to 85 C.

(33) Another embodiment of the present invention purification is carried out at temperature range about 70 C. to 90 C., but preferably temperature is 75 C. to 85 C.

(34) Throughout the description and claims the word comprise and variations of the word are not intended to exclude other technical features, additives, components, or steps. The content of the abstract of the present application is incorporated herein as reference. Additional objects, advantages and features of the invention will become apparent to those skilled in the art upon examination of the description or may be learned by practice of the invention. The following examples are provided by way of illustration, and is not intended to be limiting of the present invention.

Example1

(35) Preparation of Indigo from Indole

(36) Indole (100 gm, 0.85 mole) was suspended in tert-Butanol (750 ml, 7.5 vol) and add Acetic acid (5.07 gm, 0.08 mole), Molybledenumhexacarbonyl (80%) (340.6 gm, 1.79 mole). Heat and maintain for 7 hrs at temperature 80-86 C. Cool the reaction mass. Filter material and wash with Methanol to yield the title compound as solid.

(37) Yield: 75 gm

Example2

(38) Preparation of Indigo Disulfonic Acid Compound from Indigo

(39) Add concentrated Sulfuric acid (380 gm, 3.8 mole) and heat to 95-105 C. Charge Indigo (100 gm, 0.38 mole) and maintain at 95-105 C. for 2 hrs. Immediate cool to room temperature and suspended in Acetic acid (1500 ml, 15 vol) at temperature 20-25 C. Stir and filter. Wash with acetic acid (100 ml, 1 vol) and Ethyl acetate (800 ml, 8 vol). Further hot slurry with Ethyl acetate (450 ml, 4.5 vol) to yield the title compound as solid.

(40) Yield: 145 gm (Solid)

(41) Chromatographic Purity (by HPLC): 90 (% area),

Example3

(42) Preparation of Indigo Disulfonic Acid Compound from Indigo

(43) Add concentrated Sulfuric acid (380 gm, 3.8 mole) and heat to 95-105 C. Charge Indigo (100 gm, 0.38 mole) and maintain at 95-105 C. for 2 hrs. Immediate cool to room temperature and suspended in Acetone (5 L, 50 vol) at temperature 0-10 C. and add Ethyl acetate (5 L, 50 vol). Stir and filter. Wash with Acetone:Ethyl acetate (1:1) to yield the title compound as solid.

(44) Yield: 145 gm (Solid)

(45) Chromatographic Purity (by HPLC): 90 (% area),

Example4

(46) Preparation of Indigotindisulfonate Sodium

(47) Indigo disulfonic acid compound (100 gm, 0.24 mole) was dissolved in water (400 ml, 4 vol) and adjusted pH 6.5 to 9 by using sodium hydroxide (19 gm, 0.48 mole) solution in water (300 ml, 3 vol). Add Acetone (500 ml, 5 vol) and stir. Filter and wash with Acetone to yield the title compound as solid.

(48) Yield: 90 gm (Solid)

(49) Chromatographic Purity (by HPLC): 97 (% area),

Example5

(50) Purification of Indigotindisulfonate Sodium

(51) Indigotindisulfonate sodium (100 gm, 0.21 mole) was suspended in water (2000 ml, 20 vol). Heat to 95-100 C. and stir for 30 min at temperature 95-100 C. Cool to 55-60 C. and add Acetone (1000 ml, 10 vol). Cool to 25-30 C. Stir for 1 hr at temperature 25-30 C. Filter and wash with Acetone: water (1:1) mixture to yield the title compound as solid.

(52) Yield: 75 gm (Solid)

(53) Chromatographic Purity (by HPLC): 99.5 (% area)