The present invention provides a process for preparation of phenols of formula I.
OH
Formula I
wherein R is one or more representing hydrogen, a halogen group selected from fluoro, chloro, bromo, iodo, and C1-C3 alkyl group optionally substituted
with one or more fluorine atom.
BACKGROUND OF THE INVENTION
The substituted phenols are valuable intermediates in the preparation of herbicides, insecticides, fungicides, and pharmaceuticals. Many substituted phenols and processes for preparation thereof are known in the literature.
U.S. Patent No. 3,914,325 provides a process for preparation of o-fluorophenol from o-fluoroaniline in an aqueous medium in presence of sodium nitrite and a mixture of phosphoric and sulfuric acid at a temperature of -5 to 50°C to form a diazonium salt of the aminobenzene, which upon heating at a temperature of about 100 to about 160°C gives corresponding phenol compound.
Chinese Application No. 105481654 describes a process for preparation of o-fluorophenol. The process involves the reaction of nitrosylsulphuric acid solution with a solution of o-fluoroaniline in an organic solvent in a tubular reactor at a temperature of 0-30°C to obtain a diazo compound. The diazo compound upon hydrolysis with aqueous copper sulphate solution at a temperature of 105°C gives o-fluorophenol product. However, the use of organic solvent makes the process costlier and tedious at a commercial scale.

Chinese Application No. 108558607 describes a process for preparation of fluorophenol in a tubular reactor by reacting fluoroaniline with nitrosyl sulfuric acid solution and urea at a temperature of 100-110°C. However, the use of urea makes the process tedious and costlier.
U.K Patent No. GB1433455 also discloses a process for preparation of phenol compound by diazotizing an aminobenzene using sodium nitrite and phosphoric acid at 120°C. The diazotisation is carried out at high temperature that results in the formation of impurities.
Also, these processes are silent about the recovery -recycle of reagents and acids used. The present invention focuses on achieving higher purity product with maximum recovery of copper sulphate and other reagents.
The present invention aims at the following improvements over the known methods for the preparation of phenols:
• Eliminating the use of organic solvent;
• Reducing the quantity of aqueous used in the process;
• Circumventing the low temperature requirement for diazotization;
• Continuously isolating the product thereby reducing the formation of impurities and ensuring high purity of the phenols.
The present invention provides an efficient process for preparation of phenols.
OBJECT OF THE INVENTION
The present invention provides an efficient, simple, and cost-effective process for preparation of phenols of formula I.
OH

Formula I
wherein R is one or more representing hydrogen, a halogen group selected from fluoro, chloro, bromo, iodo, and C1-C3 alkyl group optionally substituted one or
more fluorine atom.
SUMMARY OF THE INVENTION
The present invention provides a process for preparation of a compound of formula I,

Formula I
wherein R is one or more representing hydrogen, a halogen group selected from fluoro, chloro, bromo, iodo, and C1-C3 alkyl group optionally substituted
one or more fluorine atom.
comprising the steps of:
a) diazotizing aniline of formula II to obtain a diazonium mixture; and
NH,

Formula II
wherein R is as represented above,
b) decomposing the diazonium mixture in presence of an acid and a catalyst to obtain the compound of formula I.

DESCRIPTION OF THE DRAWING
Figure 1: It is a continuous flow reactor equipped with dosing pump PI and P2 having pressure gauge P. PI and P2 are further connected with mass flow controller MFC. The reactor is further equipped with another pressure gauge P and back pressure regulator Bl. The back pressure regulator is further connected with a sample collector and product collection line.
DETAILED DESCRIPTION OF THE INVENTION
In first aspect, the present invention provides a process for preparation of a compound of formula I,

Formula I
wherein R is one or more representing hydrogen, a halogen group selected from fluoro, chloro, bromo, iodo, and C1-C3 alkyl group optionally substituted
one or more fluorine atom.
comprising the steps of:
a) diazotizing aniline of formula II to obtain a diazonium mixture; and
NH,

Formula II

wherein R is as represented above,
b) decomposing the diazonium mixture obtained in step a) in presence of an acid and a catalyst to obtain the compound of formula I.
In an embodiment, the decomposition of the diazonium mixture is carried out by
a) simultaneously charging diazonium mixture and an aqueous solution of catalyst into a preheated solution of water, catalyst and an acid to obtain reaction mixture; and
b) continuously isolating phenol of formula I from reaction mixture.
In another embodiment, the preparation of a compound of formula I is carried out without using any organic solvent.
In another embodiment, the compound of formula 1 is obtained by
a) decomposing the diazonium mixture with an acid in presence of a catalyst;
b) isolating the compound of formula I;
c) adding an "acid compatible solvent" to the remaining reaction mass to recover catalyst; and
e) recovering the acid and the solvent.
In another embodiment, the decomposition is carried out in presence of a reducing agent.
As used herein, the compound of formula II represents aminobenzenes selected from a group consisting of aniline; o-fluoroaniline; m-fluoroaniline; p-fluoroaniline; o-chloroaniline; m-bromoaniline; p-iodoaniline; o-, m- and p-trifluoromethylaniline; o-, m-, and p- nitroaniline; o-methyl aniline; m-ethylaniline and p-butylaniline or the like.
As used herein, the compound of formula I represents phenols selected from a group consisting of phenol; o-fluorophenol; m-fluorophenol; p-fluorophenol; o-chlorophenol; m-bromophenol; p-iodophenol; o-, m- and p- trifluoromethvlphenol;

o-, m-, and p- nitrophenol; o-methylphenol; m-ethylphenol; and p-butylphenol or the like.
In an embodiment of the present invention, the step of diazotization is carried out using diazotizing reagents selected from a group consisting of sodium nitrite, potassium nitrite, and nitrosylsulphuric acid in presence of an acid or a mixture thereof.
The acid is selected from a group consisting of sulphuric acid, phosphoric acid in pure form, a mixture of sulphuric acid and phosphoric acid.
In an embodiment, the molar ratio of an acid with respect to aniline of formula II is used in the range of from 1-2.
In an embodiment, the molar ratio of a diazotising agent with respect to aniline of formula II is used in the range from 1-1.3.
In an embodiment, diazotisation is carried out at a range of 0-35°C, preferably 20-35°C or most preferably in the range of 25-30°C
As used herein, "catalyst" refers to a copper catalyst. The 'copper catalyst' is selected from copper or its salts containing the cuprous and cupric ions such as copper, copper sulphate, copper halides, copper phosphate and copper oxide. Preferably, copper sulphate" refers to copper sulphate pentahydrate. The molar ratio of copper sulphate is in the range of 0.3 to 1.0 equivalents, preferably in the range of 0.5 to 0.7 equivalents.
In a preferred embodiment, the catalyst used is copper sulphate pentahydrate.
In another preferred embodiment, the catalyst used is copper.
In an embodiment, the reaction of halo substituted aniline of formula II is carried out with a nitrosylsulphuric acid solution. The nitrosylsulphuric acid solution contains nitrosylsulphuric acid and an acid.
In an embodiment, the concentration of the solution of nitrosylsulphuric acid is in the range of 35-40% by weight.

In an embodiment, the solution of nitrosylsulphuric acid is added dropwise to halo substituted aniline of formula II. The nitrosylsulphuric acid is added in 4-5 hours.
In a preferred embodiment, the 40% solution of nitrosylsulphuric acid is added dropwise to the halo substituted aniline of formula II.
The reaction of halo substituted aniline of formula II with a solution of nitrosylsulphuric acid is carried out at a temperature in the range 20 to 35°C.
In an embodiment, the molar ratio of a nitrosylsulphuric acid w.r.t halo substituted aniline of formula II is used in the range from 1-1.13.
In an embodiment, the diazotization reaction is performed at 20 to 35°C.
In an embodiment, the molar ratio of an acid w.r.t substituted aniline of formula II is used in the range of from 1-2.
In another embodiment the step of diazotization is carried out using sodium nitrite in presence an acid.
In another embodiment of the present invention, the step of decomposition is carried out in presence of an acid or a mixture thereof.
In another embodiment of the present invention, the step of diazotization is carried out using sodium nitrite followed by decomposition is presence of a mixed acid system.
The 'mixed acid system' represents mixture of phosphoric acid and sulfuric acid in a ratio of 4:1 for diazotization and 2:0 for decomposition.
In another embodiment of the present invention, the step of diazotization is carried out using nitrosylsulphuric acid followed by decomposition in presence of acid.
In an embodiment, a diazotized reaction mass is added slowly into a mixture of catalyst and an acid slowly at a temperature in the range of 135 to 140°C to give better solubility.

In an embodiment, the process of the present invention is carried out in a batch mode.
In an embodiment of the present invention, the decomposition reaction is carried out at a temperature in the range 130°C to 140°C. The high temperature range prevents the formation of excessive and uncontrollable gas formation and significantly reduce by-product coupling reaction.
In an embodiment of the present invention, the suitable reducing agent is selected from a group consisting of sulphamic acid or the like. The sulphamic acid can be in-situ generated from compounds such as sulphamide, or sulphamates such as ammonium sulphamate, and the like. However, a most preferred reducing agent is sulphamic acid as it helps in removal of nitro related impurities more effectively than urea.
In an embodiment, 2-fluoroaniline is diazotised using nitrosyl sulfuric acid and decomposed using copper sulphate pentahydrate as catalyst and sulphamic acid as reducing agent.
In another embodiment of the present invention, the step of diazotization is carried out using nitrosylsulphuric acid in presence of sulphuric acid.
The nitrosylsulphuric acid used for present invention is available as 35-40% solution.
In another embodiment the step of diazotization is carried out using sodium nitrite in presence of sulphuric acid. The molar ratio of sulphuric acid to aniline is in the range from 2.0-2.5 moles.
The phenol is continuously collected from reaction mixture. The embodiment of present invention avoids use of any organic solvent for reaction and product isolation.
In another embodiment, the present process provides a solid free process for preparation of a phenol of formula I. The solid free process is industrially more feasible and easier to handle

In another embodiment of the present invention the process is carried out in semi-batch mode or in continuous flow mode.
In an embodiment, present invention provides a process for recovery of catalyst and acid. This helps in decreasing process cost and effluent.
In another embodiment of the present invention, the step of diazotisation is carried out in a continuous mode, wherein an aqueous solution of sulphuric acid and 2-fluoroaniline are added into a coiled reactor at 50-55°C simultaneously, followed by addition of a solution of sodium nitrite at 25-30°C to form diazonium salt solution
In another embodiment of the present invention, the step of diazotization in a continuous mode is followed by step of decomposition in continuous mode.
In another embodiment of the present invention, the step of diazotization in a continuation mode to form a diazonium salt solution is followed by its addition to a solution of copper sulphate and an acid in continuous mode.
In another embodiment of the present invention, the step of diazotization in a continuation mode to form a diazonium salt solution is followed by its addition to a solution of copper sulphate and an acid in continuous and simultaneous mode.
In another embodiment of the present invention, the step of diazotisation is carried out in a continuous mode, wherein an aqueous solution of sulphuric acid and 2-fluoroaniline are added into a coiled reactor at 50-55°C simultaneously, followed by addition of diazotization agent at 25-30°C to form diazonium salt solution.
In another embodiment of the present invention, the step of diazotisation is carried out in a continuous mode, wherein an aqueous solution of sulphuric acid and 2-fluoroaniline are added into a coiled reactor at 50-55°C simultaneously, followed by addition of nitrosyl sulphuric acid at 25-30°C to form diazonium salt solution.
In another embodiment of the present invention, the step of diazotisation is carried out in a continuous mode, wherein an aqueous solution of sulphuric acid and 2-fluoroaniline are added into a coiled reactor at 50-55°C simultaneouslv followed

by addition of a solution of sodium nitrite at 25-30°C to form diazonium salt solution.
In another embodiment of the present invention, the process is carried in a continuous flow reactor of figure 1, equipped with dosing pump PI and P2 having pressure gauge P, wherein PI and P2 are further connected with mass flow controller MFC. The reactor is further equipped with another pressure gauge P and back pressure regulator Bl. The back pressure regulator is further connected with a sample collector and product collection line.
In an embodiment, a diazotized reaction mass is added slowly into a mixture of catalyst and an acid slowly at a temperature in the range of 135 to 140°C to give better solubility.
In an embodiment, the solvent used for recovery of copper catalyst is a high boiling "acid compatible solvent" having good stability in acidic conditions. The "acid compatible solvent" has boiling points more than 100°C in the range of 100°C to 160°C and is selected from a group consisting of monochlorobenzene, dichlorobenzene, methyl isobutyl ketone and mesitylene.
In another embodiment, the recovery of catalyst involves addition of acid compatible solvent, azeotropic removal of water and filtering out the copper catalyst. The present process involves more than 95% recovery of copper catalyst that significantly improves the cost effectiveness of the process at commercial scale.
In another embodiment, the step of recovering the acids and the solvent involves layer separation followed by isolation of the acid and the solvent from the respect layers. The present process involves more than 90% recovery of acids and solvents used.
The step of recovery of various reagents and solvents not only reduces the cost of the present process but also eliminates generation of waste and effluent.

The compound of formula I is obtained with a purity greater than 95%, more preferably greater than 98%.
The compound of formula II used as a reactant may be prepared by any method known in the prior art or may be obtained commercially.
The compound of formula I is obtained simultaneously from reaction mass along with water.
The completion of the reaction was monitored by gas chromatography through available derivatization methods.
Unless stated to the contrary, any of the words "comprising", "comprises" and includes mean "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.
EXAMPLES
Example 1: Preparation of 2-fluorophenol
Water (796.22g, 24.55moles) and sulphuric acid (98%, 360.36g, 2.00 moles) were charged in a glass reactor to form a reaction mixture and the mixture was heated to 60-65°C. 2-Fluoroaniline (200g, 1.00 moles) was then added dropwise into it and the mixture was stirred for 1 hour. The reaction mass was gradually cooled to 20-35°C and then a solution of nitrosylsulphuric acid (40%, 700g, 1.13moles) was added dropwise into it in 4-5 hours to form diazonium salt solution. Charged sulphamic acid (61.4g) in the reaction mass at 20-35°C lot wise and stirred for an

hour. In another reactor a mixture of copper sulphate pentahydrate (158g, 0.70moles), water (lOOg, 3.10moles) and sulphuric acid (98%, 213g, 1.18moles) was heated to a temperature of 135-140°C, and above formed diazonium solution was slowly added to it in 12-14 hours to obtain 2-fluorophenol. The product 2-fluorophenol was continuously collected along with water.
Yield: 85%; Purity: 98.6%
Example 2: Preparation of 2-fluorophenol.
Water (90g, 5.55moles), o-phosphoric acid (85%, 361g, 3.48 moles) and sulfuric acid (91g, 1.1 moles) were charged in a reactor and heated to a temperature range of 60-65°C to form a reaction mixture. 2-Fluoroaniline (200g, 1.00 moles) was added dropwise into the reaction mixture and stirred for an hour. The reaction mass was gradually cooled to a temperature of 0-5°C followed by dropwise addition of a solution of sodium nitrite (70g, 1.13moles) and water (90g, 5.55moles) into it in 2-3 hours to form diazonium salt solution. In another reaction vessel, copper sulphate pentahydrate (158g, 0.70moles) and phosphoric acid (213g, 2.05moles), were heated to a temperature of 135-140°C. The freshly prepared diazonium salt solution was added drop wise to the above reaction mixture while maintaining temperature 135-140°C. The product 2-fluorophenol (119g) was continuously collected along with water.
Yield: 80%; Purity: 98%
Example 3: Preparation of 2-fluorophenol.
Water (382g, 23.7moles) and sulphuric acid (98%, 180g, 2.0moles) were charged into a reactor and heated the solution to 60-65°C. 2-Fluoroaniline (lOOg, 1 .OOmoles) was added dropwise to form salt solution. The reaction mixture was stirred for another an hour at 60-65°C and then cooled to 0-5°C. A solution of nitrosyl sulphuric acid (350g, 40%) was added in 4-5 hours at 0-5°C to obtain diazonium solution.

In another reaction vessel, copper sulphate pentahydrate (80g, 0.3moles), water (71g, 4.4moles) and sulphuric acid (106g, l.lmoles) were heated to a temperature of 135-140°C. Charged above diazonium salt solution to the above reaction mass in 12-14 hours at 135-140°C and 2-fluorophenol was continuously collected.
Recovery of o-phosphoric acid from the reaction mixture of Example 2:
After product isolation from the reaction mixture, water was removed azeotropically at reflux temperature by introducing monochlorobenzene in a mixture. Thereafter the reaction mixture was cooled to 60-70°C. The resultant slurry was filtered and washed with hot monochlorobenzene (500g, 4.93moles) to afford upper crude copper salt and lower filtrate. Charged water (150g, 9.25moles) to the lower filtrate, stirred and separated the layers. Lower acid layer was used as such in subsequent batches with recovery more than 90% (mixed acid 574g of 48% of o-phosphoric acid and 10% of sulfuric acid) and upper organic layer was distilled out at 60-70°C under 200-3OOmmHg vacuum with monochlorobenzene recovery 90% and purity of 99.5%.
Recovery of copper sulphate from copper salt:
Crude copper salt (298g) and water (750g, 46.27moles) were added to a reaction vessel. Charged aqueous sodium hydroxide solution (48%) dropwise to adjust pH 9-10 at 25-30°C. The reaction mixture was heated for another 4-5 hours at 85-90°C followed by filtration. Obtained solid was washed with water to get copper oxide (300g, 18.5moles), which was further treated with 98% sulfuric acid to obtain pure copper sulphate with 96% of recovery.
Example 4. Preparation of 2-fluorophenol
Water (242g, 15.0eq) and sulphuric acid (98%, 180g, 2.0eq) were charged into a reaction vessel. The solution was heated to 55°C and dropwise added 2-fluoroaniline (lOOg, l.Oeq) to form a salt solution. The reaction mixture was stirred for 1.0 hour at 55°C and then cooled to 30°C. A solution of nitrosylsulphuric acid (350g, 1. leq, 40%) was added in reaction mixture at 30°C in 4-5hours to obtain diazonium salt solution

An aqueous solution of copper sulphate was prepared (solution B) by dissolving copper sulphate pentahydrate (65g, 0.288eq) in water (14lg, 8.7eq).
Copper sulphate pentahydrate (15g, 0.06eq), water (71g, 4.4eq) and sulphuric acid (106g,1.18eq, 98%) were charged in a reactor and heated to 135-140°C. Then, simultaneously diazonium salt solution and aqueous copper sulphate solution were charged at a constant rate in 12-14 hours into the reactor. Formed 2-fluorophenol was continuously collected.
Purity (GC): 98.5%
Yield: 86%
After product collection in example 1, solid copper sulphate and sulphuric acid were recovered.
Recovery percentages from residue:
Monochlorobenzene: 95%; Copper sulphate: 92%; Sulphuric acid: 96%
Example 5. Preparation of 2-fluorophenol in continuous flow reactor
Water (242g, 15.0eq) and sulphuric acid (180g, 2.0eq, 98%) were charged into a reaction vessel. The solution was heated to 55°C and dropwise added 2-fluoroaniline (lOOg, l.Oeq) to form salt solution. The reaction mass was stirred for 1.0 hour at 55°C and then cooled to 30°C. A solution of nitrosylsulphuric acid (350g, 1. leq, 40%) was added in the reaction mass at 30°C in 4-5 hours to obtain diazonium salt solution. An aqueous solution of copper sulphate was prepared by dissolving copper sulphate pentahydrate (80g, 0.35eq) in water (213g, 13.14eq).
Then, simultaneously diazonium salt solution and copper sulphate solution were charged into a preheated flow reactor at 138-140°C at a constant rate in 12-14 hours. Collected the mass from product collection line of flow reactor and extracted with dichloromethane to get 2-fluorophenol.

WE CLAIM

1. A process for preparation of a compound of formula I,
OH

Formula I
wherein R is one or more representing hydrogen, a halogen group selected from fluoro, chloro, bromo, iodo, and C1-C3 alkyl group optionally substituted
with one or more fluorine atom.
comprising the steps of:
a) diazotizing aniline of formula II to obtain a diazonium mixture; and

Formula II
wherein R is as represented above,
b) decomposing the diazonium mixture in presence of an acid and a catalyst to obtain the compound of formula I.
2. The process as claimed in claim 1, wherein decomposition of the diazonium mixture further comprises the steps of:
a) simultaneously charging diazonium mixture and an aqueous solution of catalyst into a preheated solution of water, catalyst and an acid to obtain reaction mixture; and
b) continuously isolating phenol of formula I from the reaction mixture.

3. The process as claimed in claim 1, wherein the compound of formula 1 is
obtained by:
a) decomposing the diazonium mixture with an acid in presence of a catalyst;
b) isolating the compound of formula I;
c) adding an "acid compatible solvent" to the remaining reaction mass to recover catalyst; and
e) recovering the acid and the solvent.
4. The process as claimed in claim 1, wherein the step of diazotization is carried out using sodium nitrite, potassium nitrite, or nitrosylsulphuric acid in presence of an acid.
5. The process as claimed in claim 1, wherein the preparation of a compound of formula I is carried out without using an organic solvent.
6. The process as claimed in claim 1, wherein the decomposition is carried out in presence of a reducing agent.
7. The process as claimed in claim 6, wherein reducing agent is selected from a group consisting of sulphamic acid, sulphamide or sulphamates.
8. The process as claimed in claim 1, wherein the "catalyst" is selected from a group consisting of copper, copper sulphate pentahydrate, copper halides, copper phosphate and copper oxide.
9. The process as claimed in claim 3, wherein the acid compatible solvent is selected from a group consisting of monochlorobenzene, dichlorobenzene, methyl isobutyl ketone and mesitylene.
10. The process as claimed in claim 1, wherein the acid is selected from a group
consisting of sulphuric acid, phosphoric acid in pure form, a mixture of sulphuric
acid and phosphoric acid.