Field of the invention
The present invention provides an improved process for decomposition of diazonium salt in semi batch andcontinuousprocessto prepare a compound of formula Ithatare valuable intermediates in agricultural and pharmaceutical chemistry.ZXRnFormula Iwherein “Z”represents carbon or nitrogenatom,“R”may be selected fromhydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxyand combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.Background of the inventionThe diazonium compounds are a group of organic compounds, which are important intermediates in the organic synthesis of dyes. It is preferred to keep diazonium salt in solution and used in situ.Chinese patent no. 101367738discloses a process forpreparation of m-fluoroaniline via thermal decomposition of diazonium salt. The thermal decomposition of diazonium salt involves the liberation of nitrogen gas at a very fast rate that is very difficult to control and make process unsafe.There is an urgentneed in the art to develop asafe, economicaland robust process fordecomposition of diazonium salt solution.
3Object of the present inventionThe object of the presentinvention is to provideanimproved, safe and economic process by controlling the exothermicity of decomposition of diazonium salt solution in semi batch process and continuousprocessto prepare a compound of formula I.ZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.Summary of the inventionThe present invention provides an improved process for the decomposition of diazonium saltin semi-batchprocessor continuousprocessmajorly focusing on controlling the exothermicityor heat of reactionof the process.The heat ofreaction is monitored for the semi batch and continuous process.First aspect of the present invention provides an improved process for decomposition of diazonium salt in semi-batch process to prepare a compound of formula I ZXRnFormula I
4wherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprisingthe steps of:a)carrying out diazotizationof a compound of formula IIusingdiazotizing agent in reactor1,RnZNH2Formula IIwherein“Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4,to obtain a diazonium salt of formula III;ZN2+X-RnFormula IIIwherein“Z”,“R”, n and X are as defined aboveb)chargingsolvent in a reactor2 and heating;c)addingdiazonium salt of formula III from reactor1 into reactor2;d)isolatingthe compound of formulaIfrom reaction mixtureof stepc).Second aspect of the present invention provides a process for decomposition of diazonium solutionin continuous process to prepare a compound of formula I wherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprisingthe steps of:a)carrying out diazotizationof a compound of formula II using diazotizing agentRnZNH2Formula IIwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4.to obtain a diazonium salt solution of formula III;ZN2+X-RnFormula IIIwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.
6b)dosing of solvent and diazonium salt of formula III simultaneouslyin reactor3at temperature T1 and a residence time R1;c)charging reactor 3output in reactor4at temperature T2 with residence time R2;d)isolating the compound of formulaI from output of reactor 4.Third aspect of the present invention provides an improved process for the decomposition of diazonium salt in semi batch or continuous processto prepare a compound of formula I having purity greater than 95%ZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.Detailed Description of the inventionThe present invention provides an improved process for decomposition of diazonium saltin semi batch and continuousprocess. Thediazonium salt reactions are very famous in chemistry and undergo substitution reaction to form different valuable compounds.As used herein, the heat of reaction is the enthalpy change when stoichiometric quantities of reactant react completely in singlereaction to form product at same temperature and pressure.
7As used herein, diazotizationrefers to process of converting aromatic amine into its diazonium salt, represented by formula III using diazotizing agentin presence of acid.The diazotizing agent may be selected from a group a consisting of organic nitrites such as butyl nitrite, tert-butyl nitrite, propyl nitrite, amyl nitrite or like and mixture thereof, inorganic nitrites such as sodium nitrite, potassium nitrite, lithium nitrite or like and mixture thereof. The molar ratio of diazotizing agent may be selected from 1-1.2 of compound of formula II. The preferred diazotizing agent for the present invention is sodium nitrite. The acid may be selected from hydrogen fluoride, hydrogen chloride, fluoroboric acid, hydrogen bromide or like and aqueous solution thereof.The diazotization reaction is carried out in presence of solvent. The solvent may be selected from aromatic solvent such as toluene, chlorobenzene, xylene; acids such as hydrogen fluoride and acid: base complex such hydrogen fluoride:pyridine.The diazotization may optionally be carried out in presence of base. The base may be selected from alkyl amine, aryl amine, alkylaryl amine or like and mixture thereof.The urea may be optionally used in diazonium salt solution as stabilizing agent in the present invention.The temperature for diazotization reaction may be selected from -10°C to 40°C, preferably -5°C to 0°C.Charging of solvent refers to the dumping of solvent in the reactor. Heating refers to the process of providing heat to the reactant using an external source to maintain a specified temperature. Dosing of solvent and diazonium salt solution refers to the slow addition of reactant in a specified time period in the reactor 3.Residence timeR1refers to the time period provided to the reactant to react in the reactor1.Residence time R2 refers to the time period provided to the reactant to react in the reactor 2.
8As used in the aspect, alkyl refers to C1-C3 carbon group, selected from agroup consisting of methyl, ethyl, isopropyl, propyl and C1-C3 carbon group substitutedwith at least with onehalogen such as chloro, fluoro, bromo, iodo may be selected from a group consisting of trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, dichloromethy, chloromethyl, 1,1,1-trifluoroethyl, 1,1,2-trifluoroethyl, 2,2,2-trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, 2-chloroethyl, 1-chloro-ethyl, 1-bromoethyl, 1-fluoropropyl, 1-bromopropyl, 2-bromopropyl, bromomethyl, dibromomethyl or like and combination thereof.Halogen used in the specification may be selected from a group consisting of fluoro, chloro, bromo and iodo.As used herein, the semi batch process refers the process modified to allow the flexibility for addition of reactant as time progress.The continuous process refers to the process, whichis in continuous motion subjecting the reactants undergoing chemical reaction and collecting product.In preferred embodiment,the present invention provides an improved process for decomposition of diazonium salt solution in semi-batch process to prepare a compound of formula I ZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprising the steps of:
a)carrying out diazotizationof a compound of formula II using diazotizing agentreactor1RnZNH2Formula IIwherein Z, R, n and X are as defined above,to obtain a diazonium salt solution of compound of formula III;ZN2+X-RnFormula IIIwherein Z, R, n and X are as defined above,b)charging solvent in a reactor2 and heating;c)adding diazonium salt solution of compound of formula III from reactor1 into reactor2 of stepb) in a given time period;d)isolating the compound of formula I from reaction mixtureof step c).In preferred embodiment,the present invention provides a process for decomposition of diazonium salt solution in continuous process to prepare a compound of formula I.ZXRn
10Formula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprising the steps of:a)carrying out diazotizationof a compound of formula II using diazotizing agentRnZNH2Formula IIwherein Z, R, n and X are as defined above,to obtain a diazonium salt solution of formula III;ZN2+X-RnFormula IIIwherein Z, R, n and X are as defined above,b)dosing of solvent and diazonium salt solution of formula III simultaneously in reactor 3at temperature T1 and a residence time R1;c)charging reactor 3 output in reactor 4at temperature T2 with residence time R2;d)isolating the compound of formula I from output of reactor 4.
11In preferred embodiment,the present invention provides an improved process for the decomposition of diazonium salt solution in semi batch or continuous process to prepare a compound of formula I having purity greater than 95%ZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected fromfluoro, chloro, bromo and iodo.In preferred embodiment, thesemi batchdecomposition of diazonium salt solutionis carried out by slow addition of diazonium salt solutionin solvent at heating. The semi batch and continuous process provides an additional advantage of safety. The controlled addition of diazonium solutioninto solvent at high temperature reduce the riskof accumulation of diazonium salt during the reaction.In preferred embodiment, the decomposition of diazonium salt solution is carried out in presence of solvent. The solvent may be selected form agroup consisting hydrocarbon such as pentane, hexane, heptane, cyclohexane, octane or like and mixture thereof; aromatic solvent such as toluene, chlorobenzene, xylene; and polar aprotic solvent such as dimethylformamide, dimethyl sulfoxide, sulfolane, dioxane, or the like and mixture thereof.In stepb)of semi batch process, solvent is charged in reactor2andheated. The solventin step b)of semi batch process is heated to 50-110°C, preferably at 60-100°C and more preferably at 80°C. The preferred solvent for the step b)is heptane and heated to 80°C. The decomposition may optionally be carried out in presence of catalyst. The catalyst may be selected from a group consisting of metal chloride such as copper
12chloride, cuprous chloride, iron chloride; metal sulfate such as copper sulfate, sodium sulfate or like and mixture thereof.In step c)of semi batch process, the addition of diazonium salt solutionis slowly addedin semi batchto solvent in a given time range. The diazonium salt solution is added slowly to the solvent of step b). The temperature range for addition of diazonium is selected from 50-100°C and more preferably at 80°C.The diazonium salt solution may be added in any time period depending up the quantity and flow in reactor 2.Inpreferred invention, the addition of diazonium salt solution is carried out by slow addition into the reactor2at 80°C. The product is isolated in step d)by any method known in the art such as layer separation, evaporation, decantation, filtration, extraction, crystallization, distillation or the like and mixture thereof.In preferred embodiment of present inventionin semi batch process, the diazonium solution is slowly added to the solvent at 80°C.The second aspect of the present invention provides a continuous process for the preparation of compound of formula I.The temperature T1 forreactor 3 of continuous process may be selected from 50-100°C and preferably 70°C. The residence time R1 may selected from 0.5 hour to 2 hour and preferably 1 hour for present invention.The temperature T2 of reactor 4 for continuous process may be used less than 100°C and preferably less than 90°C and more preferably 80°C. The residence time R2 may be selected from 0.5 hour to 2 hour and preferably 1 hour for present invention. The reactor 3 output of continuous process is passed to the reactor 4 and allowed to decompose at 80°C. In preferred embodiment of continuous process, the solvent and diazonium salt solution is dosing continuously in a reactor3at temperature range of 50-100°C, preferably at 70°C with a residence time of 1 hr. The outcome of the reactor3 is carried
13out toreactor 4 at 70° C with a residence time of 1 hour. The output of reactor 4 is carried for isolation compound of formula IThe reactant used for the present invention of formula II may be prepared by the methods present in the art or can be obtained commercially.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. ExampleExample 1: Preparation of 3-Fluoro-4-methylbenzonitrilein semi batch processDiazonium salt of 3-amino-4-methylbenzonitrile was prepared via diazotization using sodium nitrite in presence of hydrogen fluoride at -5-0°C. Heptane was charged in a separate reactor and heated to 80°C. Diazonium salt solution was slowly added to the heptane reactor in 1.5-2 hours. The reactor mass was stirred for 1 hour at 80°C and isolated the 3-fluoro-4-methylbenzonitrile.Example 2: Preparation of 3-Fluoro-4-methylbenzonitrile in continuous processDiazonium salt of 3-amino-4-methylbenzonitrile was prepared using sodium nitrite in presence of hydrogen fluoride at -5-0°C. Heptane and diazonium salt solution were chargedin a reactor1 at 70°C with residence time of 1 hour. The output of the reactor
14was charged in reactor2 kept at 80°C with residence time of 1 hour. The 3-fluoro-4-methylbenzonitrile was isolated from reactor2 output.Semi-batch process examplesExample 3: Preparation of 4-chloro-2,6-dimethylbromobenzeneDiazonium salt of 4-chloro-2,6-dimethylaniline was prepared using aqueous hydrogen bromide in presence of butyl nitrite at -5-0°C. Heptane was charged in the reactor and heated to 80°C. Diazonium salt solution was added slowly to the heptaneat 80°C in 1-2 hours and stirred for 2 hours at 80°C. The 4-chloro-2,6-dimethylbromobenzene was isolated from the reaction mass.Example 4: Preparation of 4-fluoro-2-trifluoromethylbromobenzeneDiazonium salt of 4-bromo-3-trifluoromethylaniline was prepared using sodium nitrite in presence of hydrogen fluoride at -5-0°C. Heptanewas charged in the reactor and heated to 80°C. Diazonium solution was added slowly to the heptane in 1-2 hour and stirred for 2 hours at 80°C. The 4-fluoro-2-trifluoromethylbromobenzene product was isolated from the reaction mass.Example 5: Preparation of 1-chloro-3-fluorobenzeneDiazonium salt of 3-chloroaniline was prepared using sodium nitrite in presence of hydrogen fluoride at -5-0°C. Heptane was charged in the reactor and heated to 80°C. Diazonium solution was added to the heptane slowly at 80°C in 1-2 hours. The reaction mass was stirred for 2 hours and isolated the 1-chloro-3-fluorobenzene product from the reaction mass. Example 6: Preparation of 1,2,4-trifluorobenzeneDiazonium salt of 2,4-difluoroanilinewas prepared using sodium nitrite in presence of fluoroboric acid at -5-0°C. Heptane was charged in a reactor and heated to 80°C. Diazonium solution was added slowly to the heptane solvent reactor in 1-2 hours. The
15reaction mass was stirred for 2 hours at80°C. The product 1,2,4-trifluorobenzene was isolated from the reaction mass.Example 7: Preparation of 2-fluoro-1,4-dimethylbenzeneDiazonium salt of 2,5-dimethylaniline was prepared using sodium nitrite in presence of hydrogen fluoride at -5-0°C and 2.5barg. Heptane was charge in the reactor and heated to 80°C. Diazonium solution was added to the heptane reactor at 80°C in 1-2 hours. The reaction mass was stirred for 2 hours at 80°C. The product 2-fluoro-1,4-dimethylbenzene was isolated from the reaction mass.Example 8: Preparation of 2-chloro-1-methy-3-nitrobenzeneDiazonium salt of 2-methyl-6-nitroaniline was prepared using aqueous sodium nitrite in presence of hydrochloric acid and cuprous chloride at -5-0°C. Heptane was charged in the reactorand heated to 80°C. Diazonium solution was added in the reactor at 80°C in 1-2 hours. The reaction mass was stirred for 2 hours at 80°C. The product 2-chloro-1-methyl-3-nitrobenzene was isolated from the reaction mass. All the examples given above may also be carried out in continuous process.

WE CLAIM:

1.Aprocess for decomposition of diazonium salt in semi-batch process to prepare a compound of formula I ZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprising the steps of:a)carrying out diazotization of a compound of formula II using diazotizing agent in reactor 1,RnZNH2Formula IIwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4,to obtain a diazonium salt of formula III;
17ZN2+X-RnFormula IIIwherein “Z”, “R”, n and X are as defined aboveb)charging solvent in a reactor 2 and heating;c)adding diazonium saltof formula III from reactor 1 into reactor 2;d)isolating the compound of formula I from reaction mixture of step c).2.A process for decomposition of diazonium solution in continuous process to prepare a compound of formula IZXRnFormula Iwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.comprising the steps of:a)carrying out diazotization of a compound of formula II using diazotizing agentRnZNH2
18Formula IIwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4.to obtain a diazonium salt solution of formula III;ZN2+X-RnFormula IIIwherein “Z” represents carbon or nitrogen atom, “R” may be selected from hydrogen, alkyl, halogen, cyano, nitro, alkoxy, hydroxy and combination thereof, n represent 0-4; X represents halogen selected from fluoro, chloro, bromo and iodo.b)dosing of solvent and diazonium salt of formula III simultaneously in reactor 3 at temperature T1 and a residence time R1;c)charging reactor 3 output in reactor 4 at temperature T2 with residence time R2;d)isolating the compound of formula I from output of reactor 4.3.The process as claimed in claim 1and claim 2, wherein compound of formula 1 is having purity greater than 95%.4.The process as claimed in claim 1 and claim 2, wherein solvent in step-b) is selected pentane, hexane, heptane, cyclohexane, octane, toluene, chlorobenzene, xylene,dimethylformamide, dimethyl sulfoxide, sulfolane, dioxaneor mixture thereof.5.The process as claimed in claim 1and claim 2, the process is carried out in the temperature range selected from -10°C to 110°C.
196.The process as claimed in claim 2, wherein R1 and R2 is selected in the range of 0.5 to 2 hour.7.The process as claimed in claim 1 and claim 2, wherein diazotizing agent is selected from butyl nitrite, tert-butyl nitrite, propyl nitrite, amyl nitrite, sodium nitrite, potassium nitrite, lithium nitrite or like and mixture thereof.8.The process as claimed in claim 1 and claim 2, wherein diazotization is carried out in presence of acid.