F0RM2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION
"A SIMPLE, SAFE AND COST EFFECTIVE PROCESS FOR PREPARATION OF HALQUINOL PRODUCT"
2. APPLICANT
NAME : LASA LABORATORY PVT. LTD.
NATIONALITY: INDIAN
ADDRESS : PLOT NO. C-l 05, MAHAD M.I.D.C.,
INOL AREA, MAHAD,
DIST- RAIGAD, PIN-402309,
.MAHARASHTRA, INDIA.
The following specification particularly describes the invention and the manner in which it is to be performed.

A SIMPLE, SAFE AND COST EFFECTIVE PROCESS FOR PREPARATION OF HALQUINOL PRODUCT
FIELD OF THE INVENTION:
Present invention relates to a simple, safe and cost effective process for the preparation of Halquinol comprising chlorinating compound of structural formula I.
BACKGROUND OF THE INVENTION:
Halquinol is a mixture of chlorinated derivative of 8-hydroxy quinoline compound of structural formula I,

and is added to animal feeds for prevention of e-coli, salmonella infection and intestinal infection. Halquinol chemically designated as mixture of 5,7-dichloro-8-uinolinol and 5-chloro-8-quinolinol. The major component of this mixture is dichloro derivative 5,7-dichloro-8-quinolinol which is within the percentage range of 57.0 to 74.0 (both inclusive), another component 5-chloro-8-quinolinol is within the percentage range of 23.0 to 40.0 (both inclusive). The third component 7-chloro-8-quinolinol may present in the mixture up to the percentage range of 4.0. Due to antifungal or anti protozoal properties, it is basically used as a veterinary feed additive and supplement. The antimicrobial effect of Halquinol derives from its ability to chelate metal ions, particularly iron, copper and zinc. In bacteria, fungi and protozoa, essential trace elements are thus removed, and enzyme functioning ceases. Additionally, Halquinol acts directly on gastrointestinal smooth muscle to slow down peristaltic activity. Thus absorption of nutrients, particularly in animals suffering from diarrhea, is enhanced, and performance criteria are improved markedly.

Since very little Halquinol is absorbed, residues are not a concern and no withholding period is needed, even for laying birds. Halquinol acts entirely in the gut and systemic activity is not necessary.
French Patent No. 1, 372, 414 disclosed process for preparing Halquinol comprising reacting compound of structural formula I, with sulfuryl chloride in glacial acetic acid at 50°C for 1.5 hours, as shown in below reaction scheme I.

Scheme I
Sulfuryl chloride tends to decompose to sulfur dioxide and chlorine and has to be consumed freshly. It has to be used very carefully due to its toxic and corrosive nature, and tear gas action. It can form fuming mixtures with water. Lots of precautions are necessary during its commercial scale use to avoid hazards and damages.
SUMMARY OF THE INVENTION:
Present invention provides a process for preparing halquinol product containing 5,7-dichIoro-8-quinolinol and 5-chIoro-8-quinolnol comprising preparing acidic aqueous solution of 8-hydroxyquinoline by mixing 8-hydroxyquinolne with water and hydrochloric acid; and chlorinating at a temperature ranging between 10°C to 20°C with chlorine gas. The obtained halquinol product contain from 57.0% to 74.0% of 5, 7-dichloro-8-quinolinol and from 23.0% to 40.0%o 5-chloro-8-quinolinol. The process involves single chlorination step and does not use any hazardous chemical. The process is simple, safe, cost effective and yielding desired components in desired percentages.

BRIEF DESCRIPTION OF THE DRAWINGS:
For more complete understanding of the features and advantages of the present invention, reference is now made to the detailed description of the invention along with the accompanying figure and in which:
Figure'l depicts IR of Halquinol
Figure 2 depicts GC Chromarogram of Halquinol
DETAIL DESCRIPTION OF INVENTION:
Present invention provides a process for preparing halquinol product containing 5,7-dichloro-8-quinolinol and 5-chIoro-8-quinoIinoI comprising preparing acidic aqueous solution of 8-hydroxyquinoline by mixing 8-hydroxyquinoline with water and hydrochloric acid; and chlorinating at a temperature ranging between 10°C to 20°C with chlorine gas. The obtained , halquinol product contain from 57.0% to 74.0% of 5, 7-dichloro-8-quinolinol and from 23.0% to 40.0% 5-chloro-8-quinolinol. The acidic aqueous solution of 8-hydroxyquinoline is prepared by mixing 8-hydroxyquinoline with water and hydrochloric acid. 8-hydroxyqufnoline is mixed with water and hydrochloric acid preferably at 15° to 25°C.
Chlorination is carried out for about 2 to 3 hours, excess chlorine is quenched with sodium metabisulphite and the obtained halquinol product is isolated by adjusting pH to 4.5 to 5.0. Preferably pH is adjusted using aqueous solution of base. Such suitable bases include but not limited to sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, aqueous ammonia, ammonium carbonate etc. Any suitable combination of more than one base is employable for pH adjustment.
To remove unwanted byproducts and impurities, the reaction mixture can be further heated to 30°C to 45CC and filtered to obtain the halquinol product. It may further washed with water to remove trace amount of inorganic impurities.
The process involves single chlorination step and does not use any hazardous chemical. The process is simple, safe, cost effective and yielding desired components in desired percentages.

The present invention is further described with the help of the following examples, which are given by way of illustration and should not be construed to limit the scope of the invention in any manner.
Example:
In clean reactor was added (400ml) water and conc, hydrochloric acid (3.84 moles), cooled, then added slowly 8-hydroxy quinoline (0.69 moles) at 20°C. Reaction mass further cooled to 10°C to 20°C and chlorinated with chlorine gas (1.06 moles) for 2 and half hours, after reaction complies excess chlorine was quenched with 50% aqueous solution of sodium metabisulphite (0.26 moles) was added, stirred for 15 minutes and further added water (500ml) and stirred for 15 to 20 minutes. Then, pH was adjusted to 4.5 with 48% solution of sodium hydroxide (3.0 moles) and heated to 35°C to 40°C. Product obtained was filtered, washed with water and dried. Yield: .135 gm.
Purity: 5,7-dichloro-8-quinolinol: 71.81% 5-chloro-8-quinolinol: 27.79%

WE CLAIM:
1. A process for preparing halquinol product containing 5,7-dichloro-8-quinolinol and 5-chloro-8-quinolinol comprising preparing acidic aqueous solution of 8-hydroxyquinoline by mixing 8-hydroxyquinoline with water and hydrochloric acid; and chlorinating at a temperature ranging between 10°C to 20°C with chlorine gas.
2. The process of claim 1, wherein the obtained halquinol product contain from 57.0% to 74.0% of 5, 7-dichloro-8-quinoIinol and from 23.0% to 40.0% 5-chIoro-8-quinolinoI.
3. The process of claim 1, wherein the acidic aqueous solution of 8-hydroxyquinoline is prepared by mixing 8-hydroxyquinoline with water and hydrochloric acid.
4. The process of claim 1, wherein the mixing 8-hydroxyquino]ine with water and hydrochloric acid is carried out at 15° to 25°C.
5. The process of claim 1, further comprising adding sodium metabisulphite to reaction mixture after chlorination.
6. The process of claim 1, wherein the obtained halquinol product is isolated by adjusting pH to 4.5 to 5.0.
7. The.process of claim'6, wherein the pH is adjusted to 4.5 to 5.0 using base.
8. The process of claim 6, further comprising heating of reaction mixture to 30°C to 45°C and filtering the halquinol product.
9. The process of claim 7, wherein the base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, aqueous ammonia, ammonium carbonate and combination thereof.
10. The process of claim 8, further comprising giving water wash to filtered halquinol product.