FORM 2
The Patent Act 1970,
(39 of 1970)
&
The Patent rule 2003
Complete Specification
(See Section 10 and Rule 13)
1. TITLE OF THE INVENTION
" PROCESS FOR THE PREPARATION OF 8-AMINO QUINOLINE DERIVATIVE "
2. APPLICANT(S)
(a) NAME : GHARDA CHEMICALS LTD
(b) NATIONALITY: INDIAN
(c) ADDRESS: B-27/29, MIDC, PHASE 1, DOMBIVLI.
DIST. THANE, PIN 421 203 MAHARASHTRA INDIA
3. PREAMBLE OF THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

PROCESS FOR THE PREPARATION OF 8-AMINO QUINOLINE DERIVATIVE
The present invention relates to a new process for preparation of 8-Aminoquinoline derivative (II) by the ammonolysis of 8-Haloquinoline derivative (I). 8-Aminoquinoline derivative is a key intermediate for the manufacture of pigment(s) as well as pharmaceutical(s)



R = H, aryl, alkyl
(0 (II)
X = Chloro, Bromo, Fluoro
It is known to prepare 8-Aminoquinolin derivative from 8-Nitroquinoline derivative by reduction process.
Preparation of 8-Aminoquinoline derivative involves Skraup synthesis using Crotonaldehyde and o-Nitroaniline with H2SO4/HCI. During the Skraup synthesis, side reactions cause lower yield and formation of side products which yields 8-Nitroquinoline of substantially poor quality. Subsequent in the hydrogenation of this 8-Nitroquinoline, low purity of nitro compound causes deactivation of the catalyst affecting its performance and recyclability .
The present invention relates to a novel process for the preparation of high purity 8-Aminoquinoline derivative by reacting aq. ammonia solution with the 8-Haloquinoline derivative in the presence of a copper catalyst.
The ammonolysis according to invention is carried out by means of aqueous ammonia solution which is 6-15 N, preferably 8-12 N so that reaction is carried out safely under economic conditions
The quantity of ammonia used is 8-25 moles per mole of 8-Haloquinoline derivative, preferably 8-12 moles per mole.
The copper catalyst can be present in the form of elemental copper, Cu(l) or Cu(ll) oxides or hydroxides or cuprous or cupric salts of mineral or organic acid, in particular halides and preferably chlorides, acetate or oxides . Cu(l) compounds are preferred.
The amount of catalyst used is 0.08 to 30 Mole%, preferably 5-15 Mole% expressed as copper, in relation to starting compound.
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This catalyst can be used on an inert support but is preferably used as such in the medium. In fact, at the reaction temperature, it solubilises, enabling to carryout the reaction under homogeneous conditions.
The process according to the invention is carried out at a convenient temperature, generally between 150-250°C and preferably between 180-220°C.
The total pressure which is most frequently autogenous pressure, is generally between 20-40 Kg./Cm2 and preferably 25-35 Kg./Cm2.
Period of pressure maintenance is 20-30 hrs. so as to get complete conversion of 8-Haloroquinoline derivative to 8-Aminoquinoline derivative. Generally 24 hrs. are sufficient to get a complete conversion.
The process accordingly to the invention can be carried out batch wise. The final product 8-Aminoquinoline derivative is separated from the mixture in the usual manner e.g.vaporisation of the ammonia and the water by releasing the pressure, it being possible for the ammonia and water to be recycled and then taking up of the residual organic phase in selective solvent.
The examples which follow are given by way of indication in order to illustrate the invention.
EXAMPLE-1
In a high pressure SS autoclave, charge 177.5 gm. of 8-Chloroquinoline derivative (I, R = CH3) & 1000 ml. aq. NH3 solution as 10 N. Add 2 gm. CuCI as a catalyst & close a reactor. Heat mass slowly to 188-190°C to get 33 - 36 Kg/cm2 pressure. Stir the mass at this temperature for 22-24 hrs. to get complete conversion. Cool mass to room temperature & remove reaction mass from reactor. Heat mass and scrub NH3 for recycle. Cool mass to room temperature & add 400 ml. methylene dichloride solvent for extraction of 8-Amino quinoline derivative. Wash MDC layer with water, concentrate up to 100°C to recover MDC (which can be recycled ) and finally vacuum distill the residual mass to get 130 gm. of 8-Aminoquinoline derivative (II, R = CH3) with GLC purity >98%
EXAMPLE-2
In a high pressure SS autoclave, charge 161 gm. of 8-Fluoroquinoline derivative ( I, R = CH3) & 1250 ml. aq. NH3 solution as 8 N. Add 3 gm. CuCI as a catalyst & close a reactor. Heat mass slowly to 190-200°C to get 32 - 34 Kg/cm2 pressure.
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Stir the mass at this temperature for 26-28 hrs. to get complete conversion. Cool mass to room temperature & remove reaction mass from reactor. Heat mass and scrub NH3 for recycle. Cool mass to room temperature & add 400 ml. methylene dichloride solvent for extraction of 8-Amino quinoline derivative. Wash MDC layer with water, concentrate up to 100°C to recover MDC (which can be recycled ) and finally vacuum distill the residual mass to get 128 gm. of 8-Aminoquinoline derivative (II, R = CH3) with GLC purity >98%
EXAMPLE-3
In a high pressure SS autoclave, charge 177.5 gm. of 8-Chloroquinoline derivative (I, R = CH3 ) & 835 ml. aq. NH3 solution as 12 N. Add 3 gm. CuCI as a catalyst & close a reactor. Heat mass slowly to 190-200°C to get 36 - 38 Kg/cm2 pressure. Stir the mass at this temperature for 22-24 hrs. to get complete conversion. Cool mass to room temperature & remove reaction mass from reactor. Heat mass and scrub NH3 for recycle. Cool mass to room temperature & add 400 ml. methylene dichloride solvent for extraction of 8-Amino quinoline derivative. Wash MDC layer with water, concentrate up to 100°C to recover MDC (which can be recycled ) and finally vacuum distill the residual mass to get 132 gm. of 8-Aminoquinoline derivative (II, R = CH3) with GLC purity >98%
EXAMPLE-4
In a high pressure SS autoclave, charge 177.5 gms of 8-Chloroquinoline derivative (I, R = CH3) & 1000 ml. aq. NH3 solution as 10 N. Add 1.6 gm. CuO as a catalyst & close a reactor. Heat mass slowly to 188-190°C to get 34 - 36 Kg/cm2 pressure. Stir the mass at this temperature for 22-24 hrs. to get complete conversion. Cool mass to room temperature & remove reaction mass from reactor. Heat mass and scrub NH3 for recycle. Cool mass to room temperature & add 400 ml. methylene dichloride solvent for extraction of 8-Amino quinoline derivative. Wash MDC layer with water, concentrate up to 100°C to recover MDC (which can be recycled ) and finally vacuum distill a residual mass to get 126 gm. of 8-Aminoquinoline derivative (II, R= CH3) with GLC purity >98%
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CLAIMS :-
1. A process for the preparation of 8-Aminoquinoline derivative ( of formula II, R = CH3) from 8-Haloquinoline derivative ( of formula I, R = CH3) in the presence of copper as a catalyst, which comprises conducting the ammonolysis with an aqueous ammonia solution.
2. The process according to claim 1 wherein the copper catalyst can be presented in the form of elemental copper, Cu(l) or Cu(ll) oxides or hydroxides or cuprous or cupric salts of mineral or organic acid, in particular halides and preferably chlorides, acetate or oxides.
3. The process according to claim 2 wherein molar ratio of catalyst is between 0.08 to 15 M%
4. The process according to claim 3 wherein the reaction is conducted at a temperature of about between 150-250°C and preferably at between 180-220°C.
5. A process according to claim 4 wherein the reaction is conducted at a pressure of about 20-40 Kg./Cm2 and preferably 25-35 Kg ./Cm2.
Dated 18th NOV. 2005
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ABSTRACT :-

X = Chloro, Bromo, Fluoro
8-Aminoquinoline derivative (II, R = CH3) is prepared from 8-Haloquinoline derivative (I, R = CH3) by reacting aq. ammonia solution with the 8-Haloquinoline derivative in the presence of Copper catalyst.
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