FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patent Rules, 2003
Complete Specification
(See section 10 and rule 13)
GREEN CONVERSION OF 2-AM1NO-4-METHYLPYRIDINE INTO
2-HYDROXY-4-METHYLPYRIDINE WITH INHERENT INFINITE
RECYCLE OF PROCESS MOTHER LIQUOR
Newreka Chemicals Private Limited, Rang Ashish, 2 Dreamland CHS, Opp Diamond Garden, Chembur, Mumbai 400 071, Maharastra, India Indian company registered under companies Act, 1956
Mr. Padia, Bhadresh K, Rang Ashish, 2 Dreamland CHS, Opp Diamond Garden, Chembur, Mumbai 400 071, Maharastra, India An Indian National
Mr. Mehata, Nitesh H, Rang Ashish, 4 Shri Sanman, Juhu Varsova Link Road,
Andheri (W), Mumbai 400 053, Maharashtra State, India
An Indian National
The following specification particularly describes the invention and the manner in
which it is to be performed.

GREEN CONVERSION OF 2-AMINO-4-METHYLPYRIDINE INTO 2-HYDROXY-4-METHYLPYRIDINE WITH INHERENT INFINITE RECYCLE OF PROCESS MOTHER LIQUOR
Field of Invention:
This invention relates to a process for conversion of 2-amino-4-methylpyridine [1] into 2-hydroxy-4-methylpyridine [2]; an intermediate for Nevirapine; an anti aids drug; with a targe number of recycles of process mother liquor as well as all other liquid streams.
Background of Invention:
Conversion of aromatic amino compounds into corresponding aromatic hydroxy! compounds find applications in the field of various groups of chemical including pharmaceuticals, dyes, agrochemicals, specialty chemicals, fine chemicals.
Hydroxy intermediates are used in latest drugs; under various phases of clinical trials, like Sulopenem [120788-07-0]; aPenem antibacterial agent, Iguratimod [123663-49-0]; an Antiarthritic drug, Sanazole [104958-90-9]; used as Radiosensitizer, Carocainide [066203-00-7]; an Antiarrhythmic drug. One of the important hydroxy compounds is 2-Hydroxy-4-methylpyridine [2], [13466-41-6]; a building block for an important and currently used 'ANTI-AIDS' drug 'Nevirapine' [3],[129618-40-2] prepared from 2-Amino-4-methylpyridine
[!]■
Out of various methods reported so far, diazotization followed by hydrolysis is widely used method.


Prior Art:
In the patent literature three patents viz. EP0516486 A2, EP0516486 Bl & US 5,541,317 are cited for the process of converting 2-amino-4-rnethylpyridine into 2-hydroxy-4-methylpyridine. In these processes about 3.3Kgs of H2SO4 per Kg of 2-hydroxy-4-methylpyridine is used. After the isolation of 2-hydroxy-4-methylpyridine, H2SO4 gets converted into sodium sulfate. Yield of the reaction is reported to be 64%.
There are several drawbacks of existing methods used for conversion of [1] into [2]. These methods generate liquid waste which is difficult to recycle. In most of the existing methods alkalies like soda ash or caustic soda is used for neutralization of excess H2SO4 required for isolation of the product. Organic solvents extraction is used for product isolation. This leads to low purity product

and low yields in hands. Generation of effluent with very high salt concentration needs a large facility for effluent treatment and disposal of wastes. These factors impose location related constraints making it mandatory for these processes to be carried out only in designated areas. In general existing processes are non-green that harms the environment to a large extent, which has become the major global concern in today's scenario.
Hence there is a need for providing a process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methytpyridine with inherent large number of recycles of reaction medium as well as all other liquid streams thereby avoiding above mentioned disadvantages and drawbacks and providing an environmentally sustainable and economical recycling process.
Objects and Advantages of Invention:
The inventors have developed a novel process for conversion of 2-amino-4-methyipyridine into 2-Hydroxy-4-methylpyridine with a large number of recycles of reaction medium.
In order to overcome the various serious drawbacks of the existing methods, either general alkali or customized Proprietary Catalytic Formulation NDHF, developed by Newreka Chemicals Pvt. Ltd. can be used which enables us to recycle reaction medium completely in the reaction. NDHF is a multifunctional formulation comprising of hydroxides of calcium or alkali metals like sodium, potassium, customized grade of activated carbon, filter aid and decolorizing agent containing silicon compounds, alumina, zirconia etc. with a range of pore sizes in appropriate composition. Use of NDHF in the process of the present invention prevents localized temperature shock; minimizes side reactions leading to generation of impurities.

An object of the process of the present invention is to provide an environmentally friendly (green) process that overcomes the problem of generation of large quantities of liquid wastes resulting from the conventional processes.
Another object of the present invention is to provide a process, wherein side reactions leading to side products formation are minimized which results in purer product formation.
A further object of the present invention is to provide a process wherein side products formation is minimized, thereby reducing the possibility of build-up of side products in reaction medium as well as all other liquid streams to a large extent and consequently making it possible to have a large number of reaction medium recycles.
A still further object of the present invention is to provide a process wherein the product is isolated by solvent extractions so that the solid spent formed is not contaminated with organic compounds.
Yet another object of the present invention is to provide a process that does not require any elaborate effluent treatment facility or a substantial solid waste disposal facility and does not have major location constraints.
Yet another object of the present invention is to provide a process whereby the end product, which is 2-Hydroxy-4-methylpyridine, have fewer impurities than produced by conventional processes.
In this invention the waste stream generated after isolation of 2-Hydroxy-4-methylpyridine is treated with NDHF developed in-house or any other customized Proprietary Catalytic Formulation or any other neutralizing agent. This treatment

completely converts the waste stream into a useful stream, which is recycled totally in the reaction sequence.
Summary of the invention:
The present invention describes a green process for the conversion of 2-Amino-4-methylpyridine into 2-Hydroxyl-4-methytpyridine in good yields in hand with a large number of recycles of reaction medium with capacity of scale-up to any level and has wide scope since it can be applied to many molecules. This method creates a closed fresh reaction medium loop. The major portion of the waste stream generated is recycled completely in the reaction sequence minimizing liquid waste in our process.
Brief Description of Figures:
Figure 1 shows flow diagram for the green reaction sequence of the present invention with a large number of recycles of reaction medium as well as all other liquid streams and the extract solvent used is Dimethylene chloride (MDCY
Figure 2 shows flow diagram for the green reaction sequence of the present invention with a large number of recycles of reaction medium as well as other liquid streams and the extraction solvent used is Diethylene chloride (EDC).
Detailed description of the invention:
The process of the present invention comprises of closed loop cycles. The green process with a large number of recycles of reaction medium as well as all other liquid streams is as shown in Figure 1 and 2.
The terminology used in this invention is explained as follows,

• Reaction Medium (RM) Reaction medium is the solvent or fresh reaction medium or a combination thereof used in the reaction and generated after performing a particular step. Reaction medium has been used as the RM at various stages of the process of the invention in its cycles following the first cycle. When this is used in start up of any cycle, it is referred to as start up RM.
• Fresh Reaction Medium (FRM) is fresh reaction medium or fresh solvent or a combination thereof used in the reaction.
• Solvent is any suitable solution that is water immiscible, either high
boiling or low boiling, aromatic or aliphatic which is linear or branched, either substituted or unsubstituted or mixture thereof.
• MDC - (Pimethvlene chloride) the solvent used for extraction.
• EDC - (Diethvlene chloride) the alternative solvent used for extraction.
• Fresh Reaction Medium Factor (FRMF) is the ratio of the weight of fresh reaction medium (FRM) with the dry weight of [1] when used in the green process.
• Reaction Medium Factor (RMF) is the ratio of the weight of the reaction medium (RM) with the dry weight of [1] when used in the green process.
• Extraction Solvent Factor (ESF) is the ratio of volume of the solvent of extraction with dry weight of [1] when used in the extraction steps of the process.
• Crystallization Solvent Factor (CSF) is the ratio of the solvent used for crystallization with the dry weight of [1] when used in the crystallization step of the process.
• Steady State of reaction medium is the composition of the reaction medium after initial recycles. This composition remains almost unchanged during subsequent recycles.

• Bleed is bleeding of part of reaction medium to take out material causing changes in the steady state composition of mother liquor.
• Cooling curve (CC) is profile of temperature verses time.
The process of the present invention uses a proprietary formulation NDHF containing electrolyte salts of various metals such as sodium, magnesium, calcium, iron, nickel, cobalt, tin, zinc, titanium, copper, manganese, and any other metals with multiple valance in the range of 0% (w/w) to 50% (w/w). The purity of the salts is variable and in the range of 50% (w/w) to 100% (w/w).
NDHF also contains hydroxides of calcium or alkali metals such as magnesium, barium, sodium, potassium in the range of 0% (w/w) to 95% (w/w); customized grade of activated carbon in the range of 0.5% (w/w) to 5% (w/w); filter aid in the range of 5% (w/w) to 95% (w/w) and decolorizing agent in the range of 0.5% (w/w) to 5% (w/w).
NDHF also contains specialty additives like polyelectrolytes, anti foaming agents, dispersing agents, emulsifying agents, mass transfer enhancing agents, anti caking agents, UV stabilizers, solubilising agents, and anti oxidants, and other such agents.
The present application also discloses a sustainable chemical process for green diazotization followed by hydrolysis of AR-NH2 into corresponding AR-OH with inherent infinite recycle of all liquid streams generated in the same.
The chemical process of the present invention basically comprises inherent infinite number of recycles of processing the mother liquor and all liquid streams generated during any of the cycles. The reaction sequence of typical cycle is represented in Figures 1 and 2 and is termed as the green process.

Figure 1 shows the complete process of the present invention along with generation and fate of all liquid streams as disclosed in the present invention, wherein the extraction solvent is MDC. Figure 2 shows the complete process of the present invention along with generation and fate of all liquid streams as disclosed in the present invention, wherein the extraction solvent is EDC.
The generation and fate of various liquid streams as shown in Figure 1 is described as follows for a batch process method. The process of the present invention is also applicable with the continuous or semi continuous recycling processes.
In the very first batch fresh reaction medium is reaction medium in start-up (Step 1.01). In subsequent batches fresh reaction medium is replaced by the liquid stream generated in the first batch.
This means that fresh reaction medium is used only in the first batch, this fresh reaction medium subsequently gets recycled in further batches in the process.
In the very first batch fresh extraction solvent is used in extractions (Steps 1.04, 1.05, 1.06). In subsequent batches the fresh extraction solvent is replaced by the liquid streams generated in the first batch.
This means that fresh extraction solvent is used only in the first batch, and which subsequently gets recycled in further batches in the process.
In the very first batch fresh crystallization solvent is used for crystallization (Step 1.08). In subsequent batches fresh crystallization solvent is replaced by the liquid streams generated in the first batch.

This means that fresh Crystallization Solvent is used only in the first batch, and which subsequently gets recycled in further batches in the process.
Stream A is generated after 1st solvent extraction of the reaction mass after addition of caustic lye. Stream B is generated after 2nd solvent extraction. Stream C is generated after 3rd MDC extraction. Stream D is generated by combination of Stream A, Stream B and Stream C and goes to solvent recovery step (Step 1.07). Stream E is generated after recovery of extraction Solvent and goes to extraction solvent storage tank. Stream F is generated from the extraction solvent storage tank and goes to the solvent extraction steps (Steps 1.04, Strep 1.05, and Stream 1.06). Stream G is generated after filtration of the product 2-Hydroxy-4-methylpyridine (Step 1.09). Stream H is generated after recovery of crystallization solvent and goes to crystallization solvent storage tank. Stream I is generated from the crystallization soWent storage tank and goes to crystallization step (Step 1.08). Stream J is generated after 3rd solvent extraction step (Step 1.06) and goes to NDHF treatment step (Step 1.10). Stream K is generated after filtration of NDHF Spent (Step 1.11) and goes to treated mother liquor storage tank. Stream L is generated from the treated mother liquor storage tank and goes to start-up step (Step 1.01).
Details of the steps involved in the process are described below, with reference to figures 1.
Green process of the present invention:
Step 1,01 - Start-up: As shown in figure 1, at the start of the process, in the first batch, fresh reaction medium (replaced by stream L taken from the treated mother liquor storage tank in subsequent batches) is charged in suitable quantities as per predetermined fresh reaction medium factor into a jacketed reactor with agitator and other known attachments known to a person skilled in the art. The weight

factor of fresh reaction medium is in the range of l(w/w) to 25(w/w), the preferable range being l(w/w) to 15(w/w); more preferable range being l(w/w) to 10(w/w) with respect to the total quantity (dry weight) of [1] (i.e. batch size).
A suitable acid is added in suitable quantity and suitable form while maintaining predetermined temperature of the reaction medium in the reaction vessel.
In the preferred embodiment of the invention, Sulfuric acid is added, maintaining temperature in a range of 0 °C to 75 °C, preferable range being 20 °C to 55 °C; more preferable range being 30 °C to 45 °C, with agitation continued for a predetermined time in the range of 0 minutes to 5 hours, preferably in the range of 0.5 hours to 3 hours and more preferably between 0.5 hours to 2.5 hours. The pH of the solution is maintained throughout this step at a predetermined level. The pH range of the solution is in the range of J to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4.
[1] is added over a period of 0 to 25 hours, either in its full amount or in any number of lots at a suitable interval of time in the temperature range of 0 °C to 100 °C, preferable range being 20 ° to 75 °C; more preferable range being 30 CC to 40 °C with agitation continued for period in the range of 1 hours to 25 hours, preferable range being 1 hour to 20 hours; more preferable range being 1 hour to 12 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4.
Step 1.02 - Reaction: The quantity (X) of [1] to be diazotized is added to the reaction vessel either in its full amount or in any number of lots followed by addition of solution of NaN02. The quantity (Y) of NaN02 to be used to make a NaNC>2 solution is calculated as 10-20% excess with respect to theoretical quantity (X1) of the NaNC>2 required to complete the reaction, and is expressed as per follows -

Quantity of NaN02:
X' = (Total quantity of [1]) * Mol. Wt of NaN02 (Theoretical)
(Mol. Wtof[l])
i.e. X' = X * Mol Wt of NaNQ2 Equation 1
Mol Wtof[l]
Therefore Y = X' + (10-20) % X' Equation 2
The solution of NaN02 is made by dissolving 'Y' quantity of NaN02 in 0.5(w/w) to 2(w/w) quantity of fresh reaction medium with respect to quantity' of NaN02. This solution in suitable quantities is charged to the reaction mass either in its full amount or in any number of lots.
NaN02 solution is added over a period of 0 to 25 hours, at a suitable interval of time in the temperature range of 0 °C to 35 °C, preferable range being 0 ° to 20 °C; more preferable range being 0 °C to 10 °C with agitation continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 20 hours; more preferable range being 1 hour to 12 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4.
Stirring is continued at the predetermined temperature and predetermined pH till reaction is complete as shown by absence of [1]. Total mass is maintained in the temperature range of 0 °C to 100 °C, preferable range being 40 °C to 100 °C; more preferable range being 60 °C to 100 °C with agitation continued for period in the range of 1 hours to 25 hours, preferable range being 1 hour to 20 hours;

more preferable range being 1 hour to 12 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4.
The distinct advantage of these conditions is that the crude [2] generated in this step contains less number of impurities, in very low quantities avoiding building-up of impurities in reaction medium as well as all other liquid streams making a large number of recycles possible.
Step 1.03 - pH Adjustment: After completion of the reaction in Step 1.02, quantity of caustic lye is charged into total mass obtained from Step 1.02 in the reactor so that pH is adjusted to a particular pH value and total mass is maintained at predetermined temperature in the range of 10 °C to 90 °C, preferable range being 25 °C to 65 °C; more preferable range being 35 °C to 45 °C and for a agitation time in the range of 0 hours to 10 hours, preferable range being 30 minutes to 5 hours, more preferable 30 minutes to 2 hours.
In the preferred embodiment of the invention, 50% caustic lye is added, maintaining temperature in a range of 0 °C to 100 °C, preferable range being 0°C to 75 °C; more preferable range being 0 °C to 45 °C, with agitation continued for a predetermined time in the range of 0 minutes to 5 hours, preferably in the range of 0.5 hours to 3 hours and more preferably between 0.5 hours to 2.5 hours. The pH of the solution is maintained throughout this step at a predetermined level. The pH range of the solution is in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5.
Total mass in the rector is then cooled to predetermined temperature in the range of 0 °C to 100 °C, preferable range being 20 °C to 60 °C, more preferable range being 30 °C to 45 °C, following a predetermined temperature curve, pH range being 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5

and maintained for 0 hours to 8 hours, preferable range being 0.5 hours to 4 hours. The benefit of this operation is that it generates free [2] from its salts.
Step 1.04 - 1st Solvent Extraction : A first quantity of a first extraction solvent determined as per the predetermined extraction solvent factor (ESF) in the range of I (v/w) to 50 (v/w), the preferable range being 1 (v/w) to 25 (v/w); more preferable range being 4 (v/w) to 6 (v/w) with respect to the total quantity of [1] (i.e. batch size) is charged to the total mass from Step 1.03 either in its full amount or in any number of lots during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours or at once, in the temperature range of 0 °C to 90 °C, preferable range being 0 ° to 60 °C; more preferable range being 20 °C to 40 °C with agitation continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5. Total mass is then settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours, in the temperature range of 0 °C to 90 °C, preferable range being 0° to 60 °C; more preferable range being 20 °C to 40 °C, Organic layer (Stream A) is then transferred to extraction solvent recovery step (Step 1.07). The benefit of this operation is that it extracts major quantity of [2] from total mass.
The first extraction solvent used for the 1st cycle of the cycles of the reaction of the invention is fresh extraction solvent. For the following cycles, the quantity of the first extraction solvent is obtained from the extraction solvent storage tank (stream F).
Step 1.05 - 2nd Solvent Extraction : A second quantity of a second extraction solvent determined as per the predetermined extraction solvent factor (ESF) in the range of 0 (v/w) to 25 (v/w), the preferable range being 0 (v/w) to 10 (v/w);

more preferable range being 0 (v/w) to 4 (v/w) with respect to the total quantity of [1] (i.e. batch size) is charged to the total mass from Step 1.04 either in its full amount or in any number of tots during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours or at once, in the temperature range of 0 °C to 90 °C, preferable range being 0 ° to 60 °C; more preferable range being 20 °C to 40 °C with agitation continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5. Total mass is then settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours, in the temperature range of 0 °C to 90 °C, preferable range being 0° to 60 °C; more preferable range being 20 °C to 40 °C. Organic layer (Stream B) is then transferred to extraction solvent recovery step (Step ] .07). The benefit of this operation is that it extracts remaining quantity of [2] from total mass.
The second extraction solvent used for the first cycle of the cycles of the reaction of the invention is fresh extraction solvent. For the following cycles, the quantity of the second extraction solvent is obtained from the extraction solvent storage tank (stream F).
Step 1.06 - 3rd Solvent Extraction : A third quantity of a third extraction solvent determined as per predetermined extraction solvent factor (ESF) in the range of 0 (v/w) to 10 (v/w), the preferable range being 0 (v/w) to 5 (v/w); more preferable range being 0 (v/w) to 3.5 (v/w) with respect to the total quantity of [1] (i.e. batch size) is charged to the total mass from Step 1.05 either in its full amount or in any number of lots during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours or at once, in the temperature range of 0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range being 20 °C to 40 °C with agitation continued for

period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours, and maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5. Total mass is then settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours, in the temperature range of 0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range being 20 °C to 40 °C. Organic layer (Stream C) is then transferred to extraction solvent recovery step (Step 1.07). The benefit of this operation is that it extracts any remaining trace quantity of [2] from total mass.
The third extraction solvent used for the first cycle of the cycles of the reaction of the invention is fresh extraction solvent. For the following cycles, the quantity of the third extraction solvent is obtained from the extraction solvent storage tank (stream F).
Step 1.07 - Extraction Solvent Recovery: Combines organic layers (Stream D) from Step 1.04 (Stream A), Step 1.05 (Stream B) and Step 1.06 (Stream C) is subjected to extraction solvent recovery wherein extraction solvent is recovered in the range of 0% (v/v) to 100% (v/v), preferable range being 25% (v/v) to 95% (v/v), more preferable range being 80% (v/v) to 85% (v/v) under pressure range of lmm of 760mm of Hg, preferable range being 50mm of Hg to 760mm of Hg, more preferable range being 350mm of Hg to 760mm of Hg, in the temperature range of 0 °C to 85 °C, preferable range being 10 °C to 85 °C, more preferable range being 30 °C to 85 °C. Recovered extraction solvent (Stream E) goes to an extraction solvent storage tank. The benefit of this operation is that the extraction solvent is recovered for subsequent recycles in the green process.
Step 1.08 - Crystallization: Crystallization solvent (Stream I) in suitable quantities as per predetermined crystallization solvent factor (CSF) either in its full amount or in any number of lots in the range of 0 (v/w) to 15 (v/w), the

preferable range being 0 (v/w) to 10 (v/w); more preferable range being 0 (v/w) to 5 (v/w) with respect to the total quantity of [1] (i.e. batch size) is charged to the total mass from Step 1.07 either in its full amount or in any number of lots during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours or at once, in the temperature range of 0 °C to 70 °C, preferable range being 0 °C to 50 °C; more preferable range being 20 °C to 40 °C with agitation continued for period in the range of 0 hours to 25 hours, preferable range being 0 hour to 10 hours; more preferable range being 0 hour to 2 hours, Total mass is then cooled following predetermined cooling curve to the temperature range of 0 °C to 70 °C, preferable range being 0 °C to 50 °C; more preferable range being 0 °C to 15 °C with agitation continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours, The benefit of this operation is that it crystallizes [2] from, total mass.
Step 1.09 - Filtration and Drying: Total mass from the Step 1.08 is filtered by known methods like nutch filter, vacuum filter, centrifuge, etc. in the temperature range of 0 °C to 85 °C, preferable range being 0°C to 30°C, more preferable range being 0 °C to 15 °C. [2] obtained is dried by known method in drying equipment like tray dryer, vacuum dryer, fluid bed dryer, etc at a temperature in the range of 0 °C to 100 °C, preferable range being 50 °C to 85 °C, more preferable range being 65 °C to 70 °C, under vacuum in the range of 1mm of Hg to 760mm of Hg, preferable range being 100mm of Hg to 760mm of Hg; more preferable range being 500mm of Hg to 760mm of Hg for a time in the range of 0 hour to 24 hours:-i preferable range being 1 hour to 10 hours following a predetermined temperature curve. The benefit of this operation is that it generates [2] containing predetermined moisture content.
Step 1.10 - NDHF Treatment: To the filtrate from the Step 1.06, (Stream J), NDHF, a Diazotization-Hydrolysis treatment agent, is charged either in its full

amount or in any number of lots. The quantity of the treatment agent is calculated by a factor of 0% (w/w) to 1 % (w/w), preferable range being 0% (w/w) to 0.8% (w/w), more preferable range being 0.05 to 0.5 % (w/w) with respect to the mother liquor to be treated. The temperature of the mixture is maintained in the range from 0 °C to 100 °C, preferably 40 °C to 80 °C, more preferably 60 °C to 70 °C. The time of charging the treatment agent is in the range of 0 hours to 5 hours, preferable range being 30 minutes to 2 hours, more preferable range being 1 hour to 1.5 hours, maintaining the pH of the mixture in the range from 1 to 9, preferable range being 2 to 7 and more preferable range being 6 to 7. Total mass charged with the treatment agent is maintained at a temperature in the range of 0 °C to 100 °C, preferably 40 °C to 80 °C, more preferably 60 °C to 70 °C for 0 hours to 15 hours, preferable range being 0.5 hours to 10 hours, more preferable range being 1 hour to 5 hours.
The benefit of this operation is that it helps in removing certain quantity of salt generated in the reaction along with the certain quantity of impurities. This bleed is vital for the large number of recycles of reaction medium as well as all other liquid streams.
Step 1.11 -Filtration: Total mass form Step 1.10 is filtered by known methods in the temperature range of 0 °C to 100 °C, preferable range being 40 °C to 80 °C, more preferable range being 60 °C to 70 °C, and at a pH in the range from 1 to 9, preferable range being 2 to 7 and more preferable range being 6 to 7. The filtrate (Stream K) is stored in the Treated Mother Liquor Storage Tank and is used (Stream L) in the start-up step (Step 1.01) in the subsequent batches as a reaction medium. Recycle of treated mother liquor impacts on process economics, yield of product [2], environmental issues and waste disposal.
In conventional process this is not happening. The mother liquor generated after completing solvent extractions is treated with known & commercially available

treatment agents/chemicals and then it is drained to an effluent treatment tank for further action or disposal.
The solid spent generated in filtration of NDHF treatment step (Step 1.11) of the present invention is crystalline and non-sticky in nature. Color of the spent ranges from gray to jet-black, typically the color is black. The pH of the spent is in the range of 3 to 9, typically the pH range being 6.5 to 7.5. The moisture content is in the range of 5% to 50%, typical range being 15% to 25%. The benefit is that this spent does not contain any substantial quantity of [X] and other organics rendering it greener and does not require substantial disposal facility.
The benefit of this operation is that it helps in removing NDHF spent from the treated mother liquor making large number of mother liquor recycles possible.
Step 1.12 - Crystallization solvent recovery: Filtrate (Stream G) from the step 1,09 is subjected to crystallization solvent recovery wherein crystallization solvent in the range of 0% (v/v) to 100% (v/v), preferable range being 85% (v/v) to 100% (v/v), more preferable range being 95% (v/v) to 99% (v/v) under vacuum range of 1mm of Hg to 760mm of Hg, preferable range being 50mm of Hg to 760mm of Hg, more preferable range being 350mm of Hg to 760mm of Hg, in the temperature range of 0 °C to 70 °C, preferable range being 10 °C to 50 °C, more preferable range being 65 °C to 70 °C. Recovered n-Hexane (Stream H) goes to crystallization solvent storage tank, and wherefrom crystallization solvent goes to Step 1.08. The benefit of this operation is that crystallization solvent is recovered for subsequent recycles in the green process.
The complete sequence is run in a complete closed loop with no liquid effluent generated as the result of the process.

Though this invention refers particularly to [1], same can be applied to other aromatic amines.
The process of the present invention works with any equipment suitable for conversion reactions such as those described herein, with any filtration technique, and filter types.
In another embodiment of the present invention, the sodium nitrite (NaN02) is substituted by nitrites of any of the group comprising calcium, magnesium, potassium, or ammonia, or any combination thereof, or^he nitrous acid (HNO2).
In yet another embodiment of the present invention, any alkali is used in place of the NDHF agent.
In a still further embodiment of the present invention, the sulfuric acid, or any other acid or salt that is used in the reaction, may be in any form such as solid or liquid, or any other form.
In a yet another embodiment of the present invention, the extraction solvent used in the reaction, may be diethylene chloride. Figure 2 shows the complete process of the present invention along with the generation and fate of all liquid streams.
Following surprising advantages are observed by the inventors as a result of the process of the present invention:
I. It is an environmentally friendly (green) process that overcomes the problem of generation of large quantities of liquid wastes resulting from the conventional processes.

2. Side reactions leading to side products formation is substantially reduced which results in purer and greener product formation.
3. Since side products are formed to a very small extent, the possibility of build¬up of side products in reaction medium as well as all other liquid streams during recycles is very low. This fact advantageously makes possible a large number of recycles of reaction medium as well as all other liquid streams in our green process.
4. The product isolation disclosed herein makes sure that the solid spent formed in the process of the present invention are not contaminated or contaminated to a very low extent with organic compounds and thus are green in nature. Consequently, the process described herein does not require any elaborate effluent treatment facility or substantial solid waste disposal facility and does not have any major location constraints unlike existing processes. This is a further advantage over the conventional processes.
5. The method disclosed herein not only is green but the 2-Hydroxy-4-methylpyridine produced at the end of the process is also greener owing to the fact that it contains fewer impurities.
6. In this invention the liquid waste stream generated after isolation of the product is treated with NDHF developed in-house or any other customized Proprietary Catalytic Formulation or any other neutralizing agent. This treatment completely converts the waste stream into a useful stream, which is recycled in the reaction itself. In this invention fresh reaction medium followed by subsequent aqueous streams are used as solvent throughout making this process greener.
7. In this invention atmospheric pressure is used throughout making it greener and safer and hence this process does not require special safety measures.

8. Temperature range used is milder leading to low energy consumption.
9. This invention relates to a process which uses fresh reaction medium as reaction media, pressure required is atmospheric and temperatures used are milder making this process green and safe.

10. A large number of recycle of fresh reaction medium used makes this process more economical since a large number of recycles results in almost theoretical isolated yield of 2-Hydroxy-4-methylpyridine.
11. This process can be applied to conversion of any primary Ar-NH2 into corresponding Ar-OH.
The following set of examples shows the recyclability of the green process described in the present invention.
EXPERIMENTAL PROCEDURE FOR NS-1 (DIAZOTIZATION)
Examples: Extraction by MDC
Fresh cycle: In a two litre capacity four necked round bottom flask equipped with stirrer, thermometer, condenser and addition port arranged in suitable heating/cooling system, Water (425ml) was charged. Sulphuric acid (225g) was charged under stirring maintaining 20°C followed by 2-Amino-4-methylpyridine [1] (lOOg) at 10 °C. Solution of Sodium Nitrite (125g) in water (175ml) was added slowly at 0 °C during 1 l-12hrs & maintained further for lhr. After ensuring complete consumption of [l]1, total mass was heated to 95 °C & maintained for lhour. MaOH (50% aqueous solution) (270g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.0 4.5. Total mass was extracted with MDC

four times; Ist extraction was with 525ml, and three extractions were with 270ml each. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (300ml) was charged at 35 °C to the residue and total mass was cooled to room temperature (normally around 30 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (90g) with melting point 128 °C (Literature2 melting point 128 °C - 130 °C), matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
First cycle: In the same set up as described above, treated mother liquor (350ml) from fresh cycle was charged. Sulphuric acid (225g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (lOOg) at 10 °C. Solution of Sodium Nitrite (125g) in water (175ml) was added slowly at 0 °C during 1 l-12hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (280g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with MDC four times; 1st extraction was with 525ml, and three extractions were with 270ml each. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (300ml) was charged at 35 °C to the residue and total mass was cooled to room temperature (normally around 30 °C) and further chilled to 10 C and maintained for 1 hour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (94g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
Fifth cycle: In the same set up as described above, treated mother liquor (220ml) from fresh cycle was charged. Sulphuric acid (225g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (lOOg) at 10 °C. Solution of Sodium Nitrite (125g) in water (175ml) was added slowly at 0 °C during 1 l-12hrs & maintained further for lhr. After ensuring complete

consumption of [1], total mass was heated to 95 °C & maintained for Ihour. NaOH (50% aqueous solution) (280g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with MDC four times; lsl extraction was with 525ml, and three extractions were with 270ml each. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (300ml) was charged at 35 °C to the residue and total mass was cooled to room temperature (normally around 30 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (96g) with melting point 129 °Ch matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
Tenth cycle: In the same set up as described above, treated mother liquor (110ml) from fresh cycle was charged. Sulphuric acid (112.5g) was charged under stirring maintaining 20°C followed by 2-Amino-4-methylpyridine [1] (50g) at 10 °C. Solution of Sodium Nitrite (62.5g) in water (87.5ml) was added slowly at 0 °C during 1 l-12hrs & maintained further for Ihr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (150g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with MDC four times; 1st extraction was with 262.5ml, and three extractions were with 135ml each. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (150ml) was charged at 35 C to the residue and total mass was cooled to room temperature (normally around 30 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (47g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
Twelfth cycle: In the same set up as described above, treated mother liquor (100ml) from fresh cycle was charged. Sulphuric acid (112.5g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (50g) at 10 °C. Solution of Sodium Nitrite (62.5g) in water (87.5ml) was added slowly

at 0 °C during 1 M2hrs & maintained further for lhr. After ensuring complete consumption of [I], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (140g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with MDC four times; 1st extraction was with 262.5ml, and three extractions were with 135ml each. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (150ml) was charged at 35 °C to the residue and total mass was cooled to room temperature (normally around 30 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (47g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
Data of all the cycles is given in the following table (Table 01)

The following table (Table 02) illustrates the savings in the quantities of various fresh solvents and fresh water used in the reaction of the present invention.


EXPERIMENTAL PROCEDURE FOR NS-1 (DIAZOTIZATION): Extraction by EDC
Fresh cycle: In a two litre capacity four necked round bottom flask equipped with stirrer, thermometer, condenser and addition port arranged in suitable heating/cooling system, Water (875ml) was charged. Sulphuric acid (450g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (200g) at 10 °C. Solution of Sodium Nitrite (250g) in water (325ml) was added slowly at 0 °C during 8hrs & maintained further for lhr. After ensuring complete consumption of [l]3, total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (484g) was charged slowly at 40 °C so as to

adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 1050ml, 2nd extraction was with 350ml, and 3rd extraction was with 105ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (600ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (166g) with melting point 128°C (Literature4 melting point 128 °C - 130 °C), matching with standard on TLC. Aqueous layer is treated with NDHF prior to recycle.
First cycle: In the same set up as described above, treated mother liquor (114ml) from fresh cycle was charged. Sulphuric acid (45g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (20g) at 10 °C. Solution of Sodium Nitrite (25g) in water (32.5ml) was added slowly at 0 °C during 8hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (49g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 105ml, 2nd extraction was with 50ml, and 3rd extraction was with 50ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (100ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (19g) with melting point 126 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to further recycle.

Fifth cycle: In the same set up as described above, treated mother liquor (450ml) from fresh cycle was charged. Sulphuric acid (225g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (100g) at 10 °C. Solution of Sodium Nitrite (125g) in water (150ml) was added slowly at 0 °C during 8hrs & maintained further for Ihr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (240g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 525ml, 2nd extraction was with 270ml, and 3rd extraction was with 270ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (300ml) was charged at 65°C to the residue and total mass was cooled to room temperature (normally around 35°C) and further chilled to 10°C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (83g) with melting point 126 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to further recycle.
Tenth cycle: In the same set up as described above, treated mother liquor (450ml) from ninth cycle was charged. Sulphuric acid (225g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (lOOg) at 10 °C. Solution of Sodium Nitrite (I25g) in water (150ml) was added slowly at 0 °C during 8hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (24 lg) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 525ml, 2nd extraction was with 270ml, and 3rd extraction was with 270ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (300ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light

brown 2-Hydroxy-4-methylpyridine [2] (89g) with melting point 129 °C, matching with standard on TLC. Aqueous layer is treated with MDHF prior to further recycle.
Fifteenth cycle: In the same set up as described above, treated mother liquor (875ml) from fourteenth cycle was charged. Sulphuric acid (450g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (200g) at 10 °C. Solution of Sodium Nitrite (250g) in water (325ml) was added slowly at 0 °C during 8hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for Ihour. NaOH (50% aqueous solution) (480g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 1050ml, 2nd extraction was with 390mJ, and 3 rd extraction was with i 05n)i. The tota) organic iayer was distilled out to 80-85% of original volume, n-Hexane (600ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (144g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to further recycle.
Twentieth cycle: In the same set up as described above, treated mother liquor (875ml) from nineteenth cycle was charged. Sulphuric acid (450g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (200g) at 10 °C. Solution of Sodium Nitrite (250g) in water (325ml) was added slowly at 0 C during 8hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (472.5g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 1050ml, 2nd extraction was

with 350ml, and 3rd extraction was with 105ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (550ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (190g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to further recycle.
Twenty-first cycle: In the same set up as described above, treated mother liquor (425ml) from twentieth cycle was charged. Sulphuric acid (225g) was charged under stirring maintaining 20 °C followed by 2-Amino-4-methylpyridine [1] (lOOg) at 10 °C. Solution of Sodium Nitrite (125g) in water (175ml) was added slowly at 0 °C during 8hrs & maintained further for lhr. After ensuring complete consumption of [1], total mass was heated to 95 °C & maintained for lhour. NaOH (50% aqueous solution) (260g) was charged slowly at 40 °C so as to adjust pH of the reaction mixture to 4.5. Total mass was extracted with Ethylene dichloride (EDC) three times; 1st extraction was with 525ml, 2nd extraction was with 270ml, and 3rd extraction was with 270ml. The total organic layer was distilled out to 80-85% of original volume, n-Hexane (350ml) was charged at 65 °C to the residue and total mass was cooled to room temperature (normally around 35 °C) and further chilled to 10 °C and maintained for lhour. Solid was then filtered and dried to get light brown 2-Hydroxy-4-methylpyridine [2] (97g) with melting point 128 °C, matching with standard on TLC. Aqueous layer is treated with NDHF prior to further recycle.

Data of all the cycles is given in the following table (Table 03),


The following table (Table 04) illustrates the savings in the quantities of various fresh solvents and fresh water used in the reaction of the present invention.


Inferences drawn from examination of Tables 01-04:
It is evident from the tables presented in this specification that:
A large number of cycles can be successfully performed in a diazotisation reaction (see Tables 01 and 03).
- The extraction temperature is much lower (38 °C to 40 °C for MDC and 50 °C for EDC) than those used in conventional reactions.
Throughout the reaction cycles, the quantity of the recycled solvents used various stages of the reaction are high. It can be seen from Table 02 that over a period of 13 cycles the savings in the fresh quantities of MDC, n-Hexane, and water are over 70%, 55% and 50% respectively.
In the case of the EDC usage, it can be seen from Table 04 that over a period of 21 cycles the savings in the fresh quantities of EDC, n-Hexane, and water are approximately 80%, 50% and 36% respectively.
It is also evident that as the number of cycles increased, the need for the fresh solvents and fresh water used in the reaction decreased significantly. Therefore the % savings in fresh quantities of solvents and water increased with the number of cycles.
In the case of MDC there's a pronounced benefit of water consumption reduction over when the EDC is used.
It is thus evident that there's a high level of recycling of all solvents used in the diazotisation reaction and the associated environmental and commercial benefits to be had from adoption of the present invention are high.
It is also evident that the process of the invention works satisfactorily using extraction solvent such as the MDC, thereby making it a viable alternative to commercially banned solvents such as the EDC. On the other

hand, when using the ECD, which is a less environmentally friendly solvent than MDC, the process of the invention mitigates the environmental costs associated with the use of EDC.
General procedure for mother liquor treatment: In a two litre capacity four necked round bottom flask equipped with stirrer, thermometer, condenser and addition port arranged in suitable heating/cooling system, mother liquor (1000ml) is charged and is heated to 65 °C. NDHF is charged at 65 °C slowly under stirring during I hour. Quantity of NDHF used is sufficient to adjust pH of the mass to 7.
After completion of NDHF charging total mass is maintained further at 65 °C for 2hours and filtered and the filtrate is cooled to 20 °C. After further stirring at 20 °C for lhour, crystallized salt is filtered out. This filtrate is stored for recycle in further batches.
Notes:
1 TLC System:
Sample Preparation:
(1) Reaction mixture; A small portion drawn from the reaction mixture is poured on ice (approximately ten times the volume of sample drawn) and pH is adjusted to 4.5 using 50% NaOH solution, Total mass is then extracted in ethyl acetate (approximately 2 times the volume of sample drawn). Ethyl acetate layer is used for TLC.
(2) Isolated [2] and standard [2]*. Sample is dissolved in ethyl acetate (5%w/v solution in ethyl acetate is prepared).
(3) [1]: Sample is dissolved in Methanol (5%w/v solution in Methanol is prepared).
Mobile Phase:
n-Hexane : Ethyl Acetate :: 1.5 : 3.5
2 US 5,541,317
3TLC System:
Sample Preparation:
Reaction mixture: A small portion drawn from the reaction mixture is poured on ice (approximately ten times the volume of sample drawn) and pH is adjusted to 4.5 using 50% NaOH solution. Total mass is then extracted in ethyl acetate (approximately 2 times the volume of sample drawn). Ethyl acetate layer is used for TLC.

Isolated [2] and standard [2]: Sample is dissolved in ethyl acetate (5%w/v
solution in ethyl acetate Is prepared).
[1]: Sample Is dissolved in Methanol (5%w/v solution in Methanol is prepared).
Mobile Phase:
n-Hexane : Ethyl Acetate :: 1.5 ; 3.5
4 US 5,541,317
While the above description contains many specificities, these should not be construed as limitation in re scope of the invention, but rather as an exemplification of the preferred embodiments thereof. Many other variations are possible. Accordingly, the scope of the invention should be determined not by the embodiments illustrated, but by the appended claims and their legal equivalents.

We claim,
1. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine (denoted as [1]) into 2-Hydroxy-4-methylpyridine (denoted as [2], comprising a reaction and extraction steps with a large number of recycles of reaction medium as well as all other liquid streams.
2. A sustainable chemical process of green conversion of [1] into [2], as described in item 1, wherein the number of cycles is preferably greater than 5, more preferably greater than 15, even more preferably greater than 20.
3. A sustainable chemical process of green conversion of [1] into [2] as described in any of items 1 and 2, wherein said green process of a typical said cycle comprises the following steps:
Step 1.01:
Creating start-up conditions for the green diazotization-hydrolysis process, said Step 1.01 further comprising the following stages:
Stage 1.01a: charging a suitable reaction medium, denoted as start-up RM, to a jacketed first reaction vessel with an agitator and other attachments known to a person skilled in the art; thereby forming the start¬up reaction mixture, denoted as SRM, wherein
the weight of the RM used being in the range of 1 to 25 times the dry weight of the [1] used in the batch, more preferably in the range from 1 to 15 times, even more preferably in the range from 1 to 10 times;
and wherein start-up RM is fresh RM (FRM) for the 1st cycle of the reaction and whereas for the following cycles, the start-up RM is obtained from the treated mother liquor storage tank, and optionally required FRM to make up loss.

Stage 1.01b: adding an acid in a suitable form and quantity, wherein said acid is preferably sulfuric acid,
and wherein the temperature of the mixture in the vessel is maintained in the range from of 0 °C to 75 °C, preferable range being 20 °C to 55°C; more preferable range being 30 °C to 45 °C,
and wherein the quantity of the acid added being such that the pH of the mixture in the vessel is maintained in the range from 1 to 9, preferably in the range from 2 to 7, more preferable in the range from 2 to 4;
Stage 1.01c: adding a suitable quantity, X, of [1] to the vessel; either in its
full amount or in any number of lots over a period of 0 to 25 hours, at a
suitable interval of time, preferably the quantity X being added in a single
lot,
and wherein the temperature is in the range of 0 °C to 100 °C, preferable
range being 20° to 75 °C; more preferable range being
30 °C to 40 °C, the mixture being agitated,
and further wherein the agitation continued for period in the range of 1 hours to 25 hours, preferable range being 1 hour to 20 hours; more preferable range being 1 hour to 12 hours,
and wherein the quantity x being such that total mass in the vessel is maintained in the pH range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4;
Step 1.02:
Stage 1.02a: adding a suitable quantity an NaNC>2 solution, wherein the quantity, Y, of NaN02 to be used to make the NaN02 solution is

calculated in terms of the theoretical quantity, X', of the NaNCh required to complete the reaction, as per the following equation:
X' = (Total quantity of [1]) x Mol.Wt of NaNCh (Theoretical)
(Mol. Wtof[l]) and wherein Y is calculated using the following equation:
Y = CX';
wherein the constant, C, is in the range between 1.1 to 1.2;
and wherein the solution of NaN02 is made by dissolving said Y quantity of NaN02 in a quantity of FRM which is in the range from 0.5 to 2 times
r,
and wherein the NaN02 solution is charged to the vessel of Step 1.02 either in its full quantity or in any number of lots,
and wherein the NaNCh solution is added to the vessel over a period in the range from 0 to 25 hours at a suitable interval of time,
and wherein the temperature of the reaction mixture is maintained in the range from 0 °C to 35 °C, preferable range being 0 ° to 20 °C; more preferable range being 0 °C to 10 °C,
and wherein agitation is continued till all [ 1 ] is consumed;
and wherein total mass is maintained in the temperature range of 0°C to 100°C, preferable range being 40 °C to 100 °C; more preferable range being 60 °C to 100°C,

and wherein agitation is continued for time period in the range of 1 hour to 25 hours, preferable range being 1 hour to 20 hours; more preferable range being 1 hour to 12 hours,
and wherein the pH is maintained in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 2 to 4,
Step 1.03:
cooling the total mass from the Step 1,02 following a predetermined cooling curve to a temperature range of 10 °C to 90 °C, preferable range being 25 °C to 65 °C; more preferable range being 35 °C to 45 °C,
and wherein a quantity of caustic lye is charged either in its full amount or in any number of lots into total mass in the reactor, preferably in a single lot;
and wherein the quantity of the caustic lye added is such that pH of the total mass is adjusted to a value in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5,
and wherein temperature is maintained in the range of 0 °C to 100 °C, preferable range being 0 °C to 75 °C; more preferable range being 0 °C to 45 °C,
and wherein agitation is continued for a predetermined time in the range of 0 minutes to 5 hours, preferably in the range of 0.5 hours to 3 hours and more preferably between 0.5 hours to 2.5 hours,

Step 1.04: adding a first quantity of a first extraction solvent to the vessel in suitable amounts as per predetermined extraction solvent factor (ESF) in the range of 1 (v/w) to 50 (v/w), the preferable range being 1 (v/w) to 25 (v/w); more preferable range being 4 (v/w) to 6 (v/w) with respect to the total quantity of [1] (i.e. batch size) to the total mass from Step 1.03 either in its full amount or in any number of lots, preferably said first extraction solvent is added in a single lot;
and wherein the addition of said first extraction solvent is done in the time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours,
and wherein temperature is maintained in the range of 0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range being 20 °C to 40 °C,
and wherein agitation continued for the time period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours,
and wherein the quantity of said first extraction solvent added is such that the pH is maintained in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5,
and wherein total mass in the vessel is settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours,

and wherein temperature is maintained in the range of 0 °C to 90 °C, preferable range being 0 ° to 60 °C; more preferable range being 20 °C to 40 °C,
and wherein organic layer separated as the result of the settlement process is transferred to the extraction solvent recovery step (step 1.07),
and wherein said first quantity of said first extraction solvent for the Ist cycle of said cycles of the reaction is fresh extraction solvent, and whereas for the following cycles, said first quantity of said first extraction solvent is obtained from the treated mother liquor storage tank,
Step 1.05: adding a second quantity of a second extraction solvent in suitable amounts as per predetermined extraction solvent factor (ESF) in the range of 0 (v/w) to 25 (v/w), the preferable range being 0 (v/w) to 10 (v/w); more preferable range being 0 (v/w) to 4 (v/w) with respect to the total quantity of [1] (i.e. batch size) to the total mass from Step 1.04 either in its full amount or in any number of lots, preferably said second extraction solvent is added in a single lot,
and wherein the addition of said second extraction solvent is done during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours,
and wherein temperature in the vessel is maintained in the range of
0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range
being 20 °C to 40 °C,

and wherein agitation of the mixture in the vessel is continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours,
and wherein the quantity of said second extraction solvent added is such that the pH is maintained in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5,
and wherein total mass in the vessel is then settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours,
and wherein temperature is maintained in the range of 0 °C to 90 °C, preferable range being, 0 °C to 60 °C; more preferable range being. 20 °C to 40 °C,
and wherein organic layer is transferred to extraction solvent recovery step (step 1.07),
and wherein said second quantity of said second extraction solvent for the 1st cycle of said cycles of reaction is fresh extraction solvent, and whereas for the following cycles, said second quantity of said second extraction solvent is obtained from the treated mother liquor storage tank,
Step 1.06: adding a third quantity of a third extraction solvent in suitable amounts as per predetermined extraction solvent factor (ESF) in the range of 0 (v/w) to 10 (v/w), the preferable range being 0 (v/w) to 5 (v/w); more preferable range being 0 (v/w) to 3.5 (v/w) with respect to the total quantity of [1] (i.e. batch size) to the total mass from Step 1.05 either in its full amount or in any number of lots, preferably in a single lot,

and wherein the addition is done during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours,
and wherein temperature is maintained in the range of 0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range being 20 °C to 40 °C,
and wherein agitation is continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 10 hours; more preferable range being 1 hour to 2 hours,
and wherein said third extraction solvent is added in such quantity that the pH is maintained in the range of 1 to 9, preferably in the range of 2 to 7, more preferable range being 4 to 5,
and wherein total mass is then settled for time period in the range of 0 to 10 hours, preferable range being 1 hour to 5 hours; more preferable range being 1 hour to 2 hours,
and wherein temperature is maintained in the range of 0 °C to 90 °C, preferable range being 0 °C to 60 °C; more preferable range being 20 °C to 40 °C,
and wherein organic layer is transferred to extraction solvent recovery step (step 1.07),
and wherein said third quantity of said third extraction solvent for the 1st cycle of said cycles of the reaction is fresh extraction solvent, and whereas

for the following cycles, said third quantity of said third extraction solvent is obtained from the treated mother liquor storage tank,
Step 1.07: recovering extraction solvent from the organic layers transferred to a distillation vessel from the extraction steps (1.04-1.06) by subjecting the mixture of the distillation vessel to a pressure in the range of 1mm of 760mm of Hg, preferable range being 50mm of Hg to 760mm of Hg, more preferable range being 350mm of Hg to 760mm of Hg,
and wherein the temperature is maintained in the range of 0 °C to
85 °C, preferable range being 10 °C to 85 °C, more preferable range being
30 °C to 85 °C,
and wherein recovered extraction solvent is stored in an extraction solvent storage tank,
Step 1.08: adding crystallization solvent in suitable quantities as per predetermined crystallisation solvent factor (CSF) to.the total mass from Step 1.07, and wherein it is added either in its full amount or in any number of lots, preferably in a single lot,
and wherein the quantity is in the range of 0 (v/w) to 15 (v/w), the preferable range being 0 (v/w) to 10 (v/w); rnore preferable range being 0 (v/w) to 5 (v/w) with respect to the total quantity of [1] (i.e. batch size),
and wherein addition is done during time period in the range of 1 to 10 hours, preferable range being 1 hour to 4 hours; more preferable range being 0.1 hour to 2 hours,

and wherein temperature is maintained in the range of 0 °C to 70 °C, preferable range being 0°C to 50°C; more preferable range being 20 °C to 40 °C,
and wherein agitation is continued for period in the range of 0 hours to 25 hours, preferable range being 0 hour to 10 hours; more preferable range being 0 hour to 2 hours,
and where after the total mass is cooled following predetermined cooling curve to the temperature range of 0 °C to 70 °C, preferable range being 0 °C to 50 °C; more preferable range being 0 °C to 15 °C,
and wherein agitation is continued for period in the range of 0 hours to 25 hours, preferable range being 1 hour to 3 0 hours; more preferable range being 1 hour to 2 hours,
Step 1.09: filtering the total mass from Step 1.08 by known methods, like nutch filter, vacuum filter, centrifuge, etc.
and wherein temperature is maintained in the range of 0 °C to 85 °C, preferable range being 0 °C to 30 °C, more preferable range being 0°Cto 15 °C,
and wherein [2] obtained is dried by known methods in drying equipments like tray dryer, vacuum dryer, fluid bed dryer, etc
and whereafter drying of [2] is done in the temperature range of 0°C to 100 °C, preferable range being 50 °C to 85 °C, more preferable range being 65 °C to 70 °C,

and wherein drying is done under vacuum in the range of 1mm of Hg to 760mm of Hg, preferable range being 100mm of Hgto 760mm of Hg; more preferable range being 500mm of Hg to 760mm of Hg,
and wherein the drying is continued for a time in the range of 0 hour to 24 hours, preferable range being 1 hour to 10 hours following a predetermined temperature curve,
Step 1.10: adding to the filtrate from the Step 1.06, a Diazotization-Hydrolysis treatment agent either in its full amount in a single lot or in any number of lots,
and wherein the quantity of said treatment agent is calculated by a factor in the range between 0% (w/w) to 1 % (w/w), preferable range being 0% (w/w) to 0.8% (w/w), more preferable range being 0.05% to 0.5 % (w/w) with respect to the amount of diazotization agent used in step 1.02 present in the mother liquor to be treated,
and wherein the time of charging the treatment agent is in the range of 0 hours to 5 hours, preferable range being 30 minutes to 2 hours, more preferable range being 1 hour to 1.5 hours,
and wherein the quantity of the agent added is such that pH of the mixture is maintained in the range from 1 to 9, preferable range being 2 to 7 and more preferable range being 6 to 7,
and wherein total mass is maintained at a temperature in the range of 0 °C to 100 °C, preferably 40 °C to 80 °C, more preferably 60 °C to 70 "C,

and wherein agitation is continued for 0 hours to 15 hours, preferable range being 0.5 hours to 10 hours, more preferable range being 1 hour to 5 hours,
Step 1.11: filtering the total mass from Step 1.10 by known methods,
and wherein temperature is maintained in the range of 0 °C to 100 °C, preferable range being 40 °C to 80 °C, more preferable range being 60 °C to 70 °C,
and wherein the filtrate is stored in a Treated Mother Liquor storage tank and is used in the start-up step (1.01a) in the subsequent batches,
and wherein the soiid spent generated in fiitt-afion ofNDHF treatment step (Step 1.11) of the present invention is crystalline and non-sticky in nature,
Step 1.12: recovering crystallization solvent from the filtrate obtained from the step 1.09 under a vacuum in the range of 1mm of Hg to 760mm of Hg, preferable range being 50mm of Hg to 760mm of Hg, more preferable range being 350mm of Hg to 760mm of Hg,
and wherein temperature range is 0 °C to 70 °C, preferable range being 10°C to 50°C, more preferable range being 65 °C to 70 °C,
and wherein recovered n-Hexane is stored in the n-Hexane storage tank,
and wherein n-Hexane from the n-Hexane storage tank is used in Step 1.08 of the subsequent batches,
whereby a single cycle of said green process is completed.

4. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methy!pyridine, comprising of reaction and extraction steps
5. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methy!pyridine, as claimed in claims 1 to 4, wherein the number of cycles is preferably greater than twenty.
6. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methylpyridine, as claimed in claims 1 to 5, wherein said chemical process is carried out in a match mode or in a continuous or semi continuous form, or any combination thereof.
7. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methylpyridine, as claimed in any of the claims
1 to 6 wherein any methods known to a person skilled in the art is used to separate 2-Hydroxy-4-methyIpyridine in place of said steps 1.09 and 1.11.
8. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into 2-Hydroxy-4-methylpyridine, as claimed in claims 1 to 7, wherein any weak alkali is used in place of NDHF in said steps 1.13.
9. A sustainable chemical process of green conversion of 2-Amino-4-methylpyridine into corresponding 2-Hydroxy-4-methylpyridine, as claimed in claims 1 to 8. wherein nitrites of any of the group comprising calcium, sodium, potassium, and ammonia, or any combination thereof, or the nitrous acid is used, in place of sodium nitrite in step 1.02.
10. A sustainable chemical process of green conversion of 2-Amino-4-
methylpyridine into 2-Hydroxy-4-methylpyridine, as claimed in claims 1 to 9,

wherein the reaction vessels may be of any type suitable for the green chemical processes, and wherein the agitators are of any suitable type, and wherein filters are of any suitable type known to a person skilled in the art.