Description:FIELD OF THE INVENTION
[001] The invention relates to an improved process for producing aryl fluorides from aryl diazonium salts and more particularly producing aryl fluorides from aryl diazonium salts in batch and continuous modes.
BACKGROUND OF THE INVENTION
[002] Aryl fluorides find extensive applications in pharmaceuticals, agriculture, and as additives in medicinal preparations. Aryl fluorides are in general prepared by the well-established Balz-Schiemann reaction wherein the aryldiazonium salt is treated with fluorinating species such as HBF4, BF3, alkali metal tetrafluoroborates and many other reagents containing facile fluoro-moieties resulting in compounds of the formula ArN2BF4 (fluorodiazonium salt) and subsequent decomposition of the fluorodiazonium salt by dediazoniation. Balz-Schiemann reaction involves introducing fluorine into an aromatic ring by diazotization of the aryl amines (also heteroaryl compounds with at least one -NH2 group) followed by fluorinative dediazoniation.
[003] Fluorodediazoniation is always performed by heating solid powder of ArN2BF4 directly. The main problems encountered during the fluorodediazoniation are non-uniform heating and the presence of water in the diazonium tetrafluoroborate which result in an uncontrollable thermal decomposition reaction and in turn resulting in many by-products. Improved methods have been established to address the constraints associated with the fluorodediazoniation such as, heating ArN2BF4 in nonreactive organic solvents such as polychlorinated aromatic solvents, thermal or photo-induced fluorodediazoniation in ionic liquids, thermal or photo-induced decomposition of aryldiazonium fluorides, and fluorodediazoniation induced by ultrasound or microwave irradiation. Still these methods have disadvantages such as requirement of additional separation steps and solvent recycling, high dependence of yield on arene substrate, and difficulties for large-scale fluorodediazoniation.
[004] Tharwat Mohy el Dine et al came out with organotrifluoroborates (RBF3‐s) as fluoride ion sources for solution‐phase fluoro‐dediazoniation in organic solvents under mild conditions. This methodology was successfully extended to a one‐pot process obviating aryl diazonium salt isolation. Sterically hindered (hetero)anilines are fluorinated under unprecedentedly mild conditions in good‐to‐excellent yields (July 2018, Chemistry - A European Journal 24(56)
DOI:10.1002/chem.201803575).,
[005] Lian Yang and Cheng-Pan Zhang studied photolysis of aryldiazonium tetrafluoroborates using polar and non-polar solvents enabling effective fluorination at a low temperature or under visible-light irradiation. PhCl and hexane were exemplified as cheap and reliable solvents for both reactions, providing good to excellent yields of aryl fluorides from the corresponding diazonium tetrafluoroborates (ACS Omega 2021, 6, 21595−21603).
[006] Zhi-qun Yu et al developed a facile and highly efficient procedure for the preparation of aromatic fluorides by Balz–Schiemann reaction via two continuous flow reactors’ set up. The continuous diazotization reactor was run at about 25 °C with residence times of 10–20 s, and the continuous fluorodediazoniation reactor was performed with a residence time of 1 min in high yields. The reaction times could be greatly reduced by increasing temperature and thereby taking advantage of superior mass and heat transfer of a continuous flow system (March 2013, Tetrahedron Letters 54(10):1261–1263, DOI:10.1016/j.tetlet.2012.12.084 ) .
[007] Patent CN108610232B disclosed the use of trivalent iodine compounds as catalysts in the Balz-Schiemann reaction, so that the Balz-Schiemann reaction can be carried out at room temperature or near room temperature when a thermochemical method is used, the reaction condition is mild, the substrate application range is wide, the reaction time is short.
[008] CN108610232A disclosed use of iodonium class compounds as the catalysts in Balz Schiemann reactions, so that Balz Schiemann reactions can be carried out at room temperature or at close to room temperature and facilitate wide scope substrate use.
[009] US5516932 disclosed preparation methods for obtaining halogenated cinnamic acids and esters thereof, processes for the preparation thereof and halogenated aryldiazonium salts in presence of modified Palladium catalyst.
[010] AU2009316478 disclosed a method of fluorinating an organic compound wherein, the method comprised providing an organic compound comprising an organostannane, a boron substituent or a silane substituent, a silver-containing compound, and a fluorinating agent, under conditions sufficient to fluorinate the organic compound, thereby providing a fluorinated organic compound.
[011] Panel Zhi-qun Yu a et al studied the use of a continuous flow reactor for Balz–Schiemann reaction for the preparation of aromatic fluorides and found that the two- continuous flow reactor setup has greatly reduced the reaction times by increasing temperature and thereby taking advantage of superior mass and heat transfer. The continuous diazotization reactor was run at about 25 °C with residence times of 10–20 s, and the continuous fluorodediazoniation was performed with a residence time of 1 min in high yields( https://doi.org/10.1016/j.tetlet.2012.12.084).
[012] Zhang Tao Zhou and others studied a Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor, since the Balz-Schiemann reaction is a straightforward strategy for preparing aryl fluorides from aryl amines, via the preparation and conversion of diazonium tetrafluoroborate intermediates. The authors successfully performed at a kilogram scale that eliminates the isolation of aryl diazonium salts while facilitating efficient fluorination. The diazotization process was performed at 10 °C with a residence time of 10 min, followed by a fluorination process at 60 °C with a residence time of 5.4 s with about 70% yield ( February 10, 2023 doi: 10.3791/64937).
[013] Kevin Simon et al studied the generation of 1,2-Difluorobenzene via a Photochemical Fluorodediazoniation Step in a Continuous Flow Mode (Org. Process Res. Dev. 2023, 27, 2, 322–330,
Publication Date: January 16, 2023, https://doi.org/10.1021/acs.oprd.2c00348).
[014] David R. Snead and others studied an improved Balz-Schiemann reaction enabled by ionic liquids and continuous processing to convert 2-cyano-5-aminopyridine to 2-cyano-5-fluoropyridine. The use of an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, BMIMBF4) as a solvent was found to be critical in achieving high assay yields and high selectivity for the fluorination vs. protonation. A process was developed to recycle and reuse the ionic liquid enabling its cost-effective use as a solvent (Tetrahedron
Volume 75, Issue 32, 9 August 2019, Pages 4261-4265).
[015] Still there are many disadvantages associated with the existing processes such as presence of by-products, explosivity during decomposition and lesser yields. Therefore, there is a need for the process wherein the aryl diazonium tetrafluoroborate salts can be synthesized and utilized under water-free conditions and at the same time can be employed in a wet condition without drying them during the decomposition to get the desired fluoroaromatic compounds. In this way we can avoid the danger associated with drying of aryl diazonium tetrafluoroborate salt. Additionally, the usage of tetrafluoroboric acid and other reagents has more influence on the cost and to make the process cost effective, using optimum quantity of these reagents is important.
[016] In order to address the drawbacks associated with the existing processes and also to obtain aryl halides with high yields and minimized hazards, the instant invention of “IMPROVED PROCESS FOR THE PREPERATION OF ARYLDIAZONIUM TETRAFLUOROBORATES AND SUBSEQUENT CONVERSION TO ARYLFLUORIDES” is taken up. The various embodiments of the instant invention “IMPROVED PROCESS FOR THE PREPARATION OF ARYLDIAZONIUM TETRAFLUOROBORATES AND SUBSEQUENT CONVERSION TO ARYLFLUORIDES” disclosed herein are definitely an improvement over the existing prior art and the instant invention offers a better method of obtaining aryl halides of the type Ar-X wherein Ar refers to substituted or unsubstituted aryl (containing mono-, polycyclic aromatic nuclei) and also heteroaryl nuclei, and X refers to mono or polyfluoride moieties. The instant invention provides a fluorodediazoniation method of obtaining aryl fluorides at comparatively milder temperature conditions and also involves the recycling of the important by-product BF3, thereby making the process eco-friendly and cost-effective. The various embodiments of the instant invention are disclosed in the following paragraphs and are better understood in the light of the examples given.
[017] The exemplary aspects of various embodiments of the invention are disclosed in the summary of the invention and all the essential aspects related to various embodiments of the invention are described in a detailed manner in the following paragraphs with specific references towards the corresponding figures as given hereunder. All the prior art references are incorporated hereby in their entirety for reference-sake and in no way taking away the novelty of the instant invention. The various aspects of the instant invention disclosed herein are definitely an improvement over the existing prior art and further stress upon the inventorship, novelty and applicability of the instant invention.
[018] OBJECTIVES OF THE INVENTION
1. To come out with an improved process for the synthesis of aryl fluorides by preparing diazonium tetrafluoroborate salt followed by decomposition of the diazonium tetrafluoroborate salt without drying it.
2. To come out with an improved process for synthesizing aryl fluorides wherein suitable solvents are used to wash the diazonium salt which avoids carry over of water to decomposition step that can lead to violent decomposition of the aryldiazonium tetrafluoroborate.
3. To come out with a process of obtaining aryl fluorides by the decomposition of aryldiazonium tetrafluoroborates wherein the decomposition of the aryldiazonium tetrafluoroborate is preceded by dissolution of the aryldiazonium tetrafluoroborate in a halogenated or non-halogenated solvent, thereby accomplishing the decomposition at comparatively milder temperature conditions.
4. To synthesize aryl fluorides from the decomposition of Aryldiazonium Tetrafluoroborates wherein recovery of boron trifluoride that is formed as a by-product is accomplished as Sodium tetrafluoroborate or HBF4 using Sodium fluoride in water/water respectively, and recycling of recovered Sodium tetrafluoroborate/HBF4 is done to synthesize Aryldiazonium Tetrafluoroborate.
SUMMARY OF THE INVENTION
[019] The exemplary embodiment of the invention discloses preparation of aryldiazonium tetrafluoroborates that undergo dediazoniation in a suitable solvent thereby producing aryl fluorides in a continuous or batch process at milder experimental conditions with the recovery of valuable by-product BF3 that can be recycled on dissolution in sodium fluoride and/or water to the reactor as feed in the form of sodium tetrafluoroborate or tetrafluoroboric acid, thereby making the process eco-friendly and cost-effective.
[020] One preferred embodiment of the invention discloses preparation of aryl tetrafluoro diazonium salt by reacting an aromatic compound carrying at least one amino group on the aromatic ring with a nitrosating agent in the presence of tetrafluoroboric acid/boron trifluoride in water in a batch or continuous mode.
[021] Another embodiment of the invention discloses the decomposition of the aryldiazonium tetrafluoroborate salt (Fluorodediazoniation) by the thermal decomposition of the aryldiazonium tetrafluoroborate salt taken in a suitable solvent to accomplish the decomposition at milder temperature conditions by replacing the diazonium part from aryl diazonium tetrafluoroborate salts with fluorine resulting in the formation of aryl fluoride or fluoroaromatic compound.
[022] Yet another embodiment of the invention discloses purification of the fluoroaromatic compound preferably by distillation to obtain the corresponding aryl fluoride with maximum purity and high yield percentage along with the recovery of the important by-product BF3 that can be fed to the reactor as the feed, on dissolution of the NaBF4 salt formed in water.
[023] One important embodiment of the invention discloses a Continuous process of preparation of aryl fluorides using scrapped surface continuous reactor followed by expanded tubular reactor, from aryl diazonium tetrafluoroborates that recycles and reemploys the generated boron trifluoride.
DETAILED DESCRIPTION OF THE INVENTION
[024] The examples of the invention and apparatus discussed herein are not limited in application to the details of the reaction methods, construction and the arrangement of components set forth in the following description or illustrated in the accompanying drawings. It will be understood by one of skill in the art that the invention is capable of implementation in other embodiments and of being practiced or carried out in various ways. Examples of specific embodiments are provided herein for illustrative purposes only and are not intended to be limiting. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
[025] Any references to examples, embodiments, components, elements or acts of the apparatus herein referred to in the singular may also embrace embodiments including a plurality, and any references in plural to any embodiment, component, element, or act herein may also embrace embodiments including only a singularity (or unitary structure). References in the singular or plural form are not intended to limit the presently disclosed apparatus, its components, acts, or elements.
[026] The use herein of “including,” “comprising,” “having,” “containing,” “involving,” and variations thereof is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. References to “or” may be construed as inclusive so that any terms described using “or” may indicate any of a single, more than one, and all of the described terms. The various embodiments of invention are described in detail herein and the various aspects of the invention are disclosed below.

[027] DEFINITIONS
Aryldiazonium tetrafluoroborate is ArN2BF4.
Tetrafluoroboric acid is HBF4.
Diazotization is a chemical reaction mechanism that involves introduction of an azo group or -N2 group into an aromatic nucleus having at least one -NH2 group.
Fluorodediazoniation is the simultaneous introduction of -F into the aromatic nucleus and removal of the diazo group.
ODCB is Ortho-dichlorobenzene.
SSCR is Scrapped surface continuous reactor.
ETR is Expanded tube reactor.
BF3/ BF3 is boron trifluoride.
Aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl or naphthyl etc.
A heteroaryl group is derived from a heteroarene (Heterocyclic compounds formally derived from arenes by replacement of one or more methine (-C=) and/or vinylene (-CH=CH-) groups by trivalent or divalent heteroatoms, respectively) by removal of a hydrogen atom from any ring atom.
[028] The various embodiments of the instant invention are disclosed fully in the following paragraphs. A person skilled in the art can easily perform the instant invention on similar lines as disclosed hereunder. The instant invention is not limited to the embodiments disclosed herein, within the scope of invention similar, nearly similar examples can be performed without deviating from the essence of the invention.
PROCESS OF OBTAINING ARYLFLUORIDES FROM ARYLDIAZONIUM TETRAFLUOROBORATES
[029] The instant invention discloses an improved process for the synthesis and isolation of Aryldiazonium Tetrafluoroborates which on decomposition result in aryl fluorides or fluorinated aryl or hetero aryl compounds with at least one -F moiety.
[030] The process for the preparation of fluoroaromatic compound involves the following steps.
STEP-1: PREPARATION OF ARYLDIAZONIUM TETRAFLUOROBORATE (DIAZONIUM SALT) OR FLUORODIAZOTIZATION:
[031] Fluoro-diazotization involves the oxidation of aryl or aromatic amines and hetero aryl compounds containing at least one -NH2 moiety, using nitrous acid followed by salt formation with a fluorinating species such as HBF4 to form diazonium tetrafluoroborate salt. These salts are prepared in aqueous solution in the presence of an immiscible solvent at low temperature preferably at 0±5 °C. The disadvantages associated with the existing processes are avoided by performing the fluoro-diazotization using HBF4 dissolved in an alcoholic solvent and the so formed aryl diazonium tetrafluoroborate is utilized without drying to get the fluoroaromatic compound on decomposition, in good amounts under anhydrous conditions (water-free). This improvement in the conditions ensured anhydrous/water-free conditions thereby avoiding explosions due to dryness. At the same time recovery of the BF3 gas formed as a by-product during the reaction as the sodium salt (NaBF4) or as HBF4 in water and recycling the same to the reaction mixture resulted in an economical and eco-friendly process. The experiments are carried out in both batch and continuous modes to obtain maximum yields. The most preferred nitrite employed for obtaining nitrous acid is Sodium nitrite. Due to the instability of nitrous acid, it is prepared in-situ by the addition of sodium nitrite in aqueous solution to a suitable acid in the molar ratio of 1 to 1.5(preferably between 1 to 1.1) of sodium nitrite to aromatic amine. The preferred ratio of water to sodium nitrite is 1 to 3 (preferably 1) by volume.
[032] Suitable inorganic acids like hydrochloric acid, sulphuric acid and tetrafluoroboric acid are used for converting sodium nitrite to nitrous acid. The preferred acid used according to present invention is hydrochloric acid. The molar ratio of the inorganic acid to sodium nitrite is 1 to 2.5 (preferably between 1 to 1.1). The preferred sequence of charging the reactor is as given here in the order of 1. aromatic amine; 2. inorganic acids; 3. tetrafluoroboric acid followed by 4. aqueous sodium nitrite solution. The aromatic amine compound was added all at once or gradually at ambient temperature. The solvent was added (if required) all at once or gradually at ambient temperature. Aqueous hydrochloric acid (35%) was added dropwise at 5 – 30 °C (preferably at ambient temperature). Freshly prepared cold tetrafluoroboric acid was added dropwise at 0 – 30 °C (preferably at ambient temperature). The addition of aqueous solution of sodium nitrite was done dropwise at 0 ± 5 °C.

GENERAL PROCEDURES
[033] Substituted or unsubstituted aryl compounds comprising of aromatic amines, polycyclic aromatic amines, substituted anilines, substituted/unsubstituted heteroaryl compounds, having at least one -NH2 group are used as reaction substrates for the diazotization reactions in the present invention wherein substituted aniline compound is having the structure as given below( wherein ‘R’ represents a substituent).

The substituted/ unsubstituted aniline compounds, aryl compounds are either monocyclic (having single benzene ring) or polycyclic (having more than one benzene nucleus such as naphthalene, etc.)

[034] The diazonium tetrafluoroborate salts are prepared by carrying out a diazotization reaction using nitrous acid followed by the addition of tetrafluoroboric acid that resulted in the formation of diazonium tetrafluoroborate salt. The diazonium tetrafluoroborate preparation consisted of the following steps.
1. Charging of the substrate containing at least one -NH2 group at ambient temperature,
2. Addition of water as solvent (if required).
3. Addition of aqueous hydrochloric acid at 5 to 30 °C to get amine hydrochloride salt.
4. Addition of freshly prepared cold tetrafluoroboric acid at 5 to 30 °C.
5. Finally, addition of aqueous solution of sodium nitrite at 0 ± 5 °C.
6. Filtration of the diazonium tetrafluoroborate salt.
7. Washing with appropriate solvent (alcoholic solvent, followed by a polar or non-polar aprotic/ protic solvent to remove water to obtain the diazonium tetrafluoroborate salt in an anhydrous, wet condition.

[035] The filtered aryl diazonium tetrafluoroborate salt is subjected to polar protic or mixture of polar protic, followed by non-polar aprotic solvent wash to obtain the diazonium tetrafluoroborate salt as a water-free wet cake. The aryl diazonium tetrafluoroborate salt wet cake thus formed is used in the next decomposition step without drying it. In this way the amount of water present in the isolated diazonium tetrafluoroborate salt is limited to a negligible amount or completely removed, thereby significantly reducing the formation of unwanted phenol and other by-products.

STEP -II DECOMPOSITION (FLUORODEDIAZONIATION):
[036] Decomposition step or fluorodediazoniation involves heating of the water-free diazonium tetrafluoroborate salt that has been obtained in Step I as a wet cake. Decomposition involves replacing the diazonium part (-N2) from aryl diazonium tetrafluoroborate salt with fluorine by thermal decomposition. Conventional fluorodediazoniation to obtain aryl fluorides involves the following hazards:

1. Decomposition of aryl diazonium tetrafluoroborate produces expensive and harmful boron trifluoride gas.
2. Aryl diazonium tetrafluoroborate salt decomposes more violently and undergoes thermal runaway.
3. The selectivity of the product varies with different solvents during decomposition, which affects the overall yield as many impurities are forming.

[037] The disadvantages and hazards associated with the existing fluorodediazoniation are addressed effectively by the instant invention as given below:
1. To recover the boron trifluoride gas metal salts such as Sodium fluoride or Potassium fluoride dissolved in in water are used.
2. Re-use of the recovered boron trifluoride made the process cost effective.
3. Decomposition of the diazonium tetrafluoroborate is done in a gradual manner.
4. The decomposition of the diazonium tetrafluoroborate is conducted after dissolving the same in a suitable solvent such as ortho-dichlorobenzene (ODCB).
5. The instant invention made the process less polluting than the previous processes as the harmful boron trifluoride gas is recovered in the form of inorganic salts and is re-employed.

PROCEDURE OF FLUORINATIVE DEDIAZONIATION OR FLUORODEDIAZONIATION
[038] Fluorinative dediazoniation or fluorodediazoniation was carried out by thermal decomposition of diazonium tetrafluoroborate by replacing the diazonium part from aryl diazonium tetrafluoroborate salts with fluorine. The process of fluorodediazoniation comprises the following steps sequentially.
1. Charging of appropriate solvent such as ODCB at ambient temperature,
2. Addition of anhydrous diazonium tetrafluoroborate in the form of wet cake.
3. Thermal decomposition of the diazonium tetrafluoroborate at appropriate temperature (it can vary between 50 to 150° C., preferably between 40° C. and 130° C).
4. Recovery of boron trifluoride from the decomposition of diazonium tetrafluoroborate, by purging the liberated boron trifluoride gas to the inorganic acid like hydrofluoric acid or metal fluorides like Sodium in water.
5. The heating was continued until the evolution of the gases has completely ceased (nitrogen followed by boron trifluoride).
6. Cooling the reaction mass to ambient temperature for the downstream.
7. Removal of residual Boron trifluoride from the reaction mass by washing or purging techniques.
8. Distillation of the final product to get the pure product namely the aryl fluoride.

[039] The instant invention optimized the quantities of all the reagents especially the requirement of tetrafluoroboric acid to make the process cost effective. It is found that the usage of tetrafluoroboric acid has more influence on the cost and to make the process cost effective using optimum quantities of these reagents is important. The instant invention provides the method of using the recovered aqueous sodium tetrafluoroborate or HBF4 as a fluorine source. Experiments are also conducted to ascertain the suitability of the method of producing aryl fluorides from aryldiazonium tetrafluoroborates by fluorodediazoniation in a continuous mode using suitable reactors to further improve the yield of aryl fluorides.

CONTINUOUS PROCESS OF PREPARING ARYL FLUORIDES OF THE FORMULA ‘AR-X’ FROM ARYLDIAZONIUMTETRAFLUOROBORATES IN FLOW REACTORS
[040] The continuous process for producing aryl fluorides from aryldiazonium fluoroborates is accomplished in 2 steps, using two flow reactors namely Scrapped surface continuous reactor (SSCR) and an expanding tube reactor (ETR). The step -I reaction of fluorodiazotization involves conversion of aryl or heteroaryl compound containing at least one -NH2 group to aryl (or heteroaryl) tetrafluoroborate salt and step-II reaction comprises of the decomposition of the salt obtained in step-I continuously in a flow reactor, wherein the continuous flow of the salt as a slurry is ensured by suspending the step-I product in solvents such as ODCB, toluene etc as cosolvent for fluorodiazotization under heating to get the desired product, namely aryl or heteroaryl fluoride along with the two gases nitrogen and BF3.
[041] Aryl/ heteroaryl compound containing at least one-NH2 group, Hydrochloric acid and Fluoroboric acid are taken in a flask below 20⁰C under stirring, which becomes a viscous white slurry after the completion of the reaction. This slurry is diluted with ODCB and used as Feed-1 of the continuous process.
[042] Sodium nitrite is dissolved in water is considered as Feed-2. These two feeds are pumped into the scrapped surface continuous reactor (SSCR) at -5 to -10οC with the flow rates of both feeds with the residence time varying in the range of 10 to 35 minutes. The material of construction for the SSCR is SS316. The agitator blade present on the inside of the SSCR (as per the design) helps to push out the formed salts continuously into the stirred tank without any choking.
[043] The stirred tank is maintained at -5 to -10οC. The salt is then drained from the bottom valve of the stirred tank and is proceeded for filtration. Filtration is carried out using the filtration cloth on Buckner funnel, under vacuum for 1 hour. The filtered salt is washed with appropriate solvent to remove water followed with ODCB wash. The wet salt is suck dried for 1 hr under vacuum and proceeded for step-2.
[044] The salt collected is made into a slurry by adding 5 volumes of ODCB and is subjected to decomposition at different residence times ranging from 50 secs to 80 secs, in an expanding tube reactor(ETR), with the utility temperature varying between 111οC and 120οC. This reaction mass containing the aryl fluoride and ODCB is collected in a 10L stirred tank with 2 condensers connected one each on inlet and outlet gas line of the 10L stirred tank, and temperature was maintained at -18 to -20οC to minimize the aryl fluoride losses. Removal of residual Boron trifluoride from the reaction mass was done by washing or purging techniques. The aryl fluoride product thus obtained is subjected to distillation to get the desired purity of the final product namely, aryl fluoride.
[045] The instant invention can be better understood with the following examples. The following examples describe the invention fully and disclose the best method of practising the same.
Example 1
Synthesis of Fluorobenzene (batch process)
[046] Diazotization: Aniline (50.0 g, 1.0 eq) was Charged into the RBF at 25 - 30 ° C under stirring and cooled the mass to 10 ± 5 °C. Con. Hydrochloric acid (55.88 g, 1.0 eq, 35 – 36% solution in water) was added dropwise over a period of 10 -15 min by maintaining the temperature at 10 ± 5 °C. Freshly prepared tetrafluoroboric acid solution (153.7 g, 1.1 eq, freshly prepared solution) was added dropwise over a period of 10 -15 min by maintaining the reaction mass temperature at 10 ± 5 °C. Further the mass was cooled to (-5) ± 5 °C and a solution of sodium nitrite (38.84 g of NaNO2, 1.05 eq in 50.0 mL water) was added dropwise over a period of 1 -2 hr by maintaining the temperature at (-5) ± 5 °C. The reaction mass was stirred at (-5) ± 5 °C for 30 – 45 min. The reaction mass was filtered, washed the bed with chilled methanol (2 x 50 mL) followed by chilled Ortho dichlorobenzene (2 x 50 mL) to get diazonium tetrafluoroborate salt as off white to pale pink solid (127 g wet) with >98% purity by HPLC. Preparation of HBF4 solution: HF solution was charged (118.2g, 4.4 eq, 40% aq. solution) into the plastic container and the mass was cooled to 10 ± 5 °C. Boric acid (36.51g, 1.1eq) was added in portion by maintaining the mass temperature at 10 ± 5 °C over a period of 1 – 1.5 h and the mass was stirred at 10 ± 5 °C for 30 – 45 min.

[047] Decomposition: Decomposition is accomplished by charging ODCB (100 mL) and diazonium tetrafluoroborate (63.5 g, lot-1) into the RBF at 25 - 30 ° C under stirring. Slowly heated the reaction mass to 53 ± 3 °C with stirring till the BF3 evolution stopped. Cooled the reaction mass to 25 ± 5 °C and added diazonium tetrafluoroborate (63.5 g, lot-2). Slowly heated the reaction mass to 53 ± 3 °C till the BF3 evaluation stopped. (N2 gas liberation followed by BF3 gas liberation is observed approximately for 2-3 h). Heated the reaction mass further to 65 ± 2 °C to ensure the complete decomposition and stirred the mass for 30 – 40 min. Cooled the reaction mass to 25 ± 5 °C, added water (150.0 mL) and separated the layers. The organic layer was distilled to get pure Fluorobenzene with >99% purity by GC (34.74 g, 67.3% yield over 2 steps). Boron trifluoride was released during this process and the same was effectively recovered by purging the outlet from the reaction into another RBF containing 20 g of sodium fluoride and 40 mL of water under stirring at ambient temperature. After the completion of the purging of boron trifluoride gas (once BF3 gas evolution is stopped), the mass was filtered to remove unreacted sodium fluoride (2.37 g) and the filtrate contains Sodium tetrafluoroborate (77.5 g, 0.421 moles) which was used for the diazotization reaction without any further purification. The recovery of the boron trifluoride was 88.1%.
Example 2
Synthesis of Fluorobenzene using recovered BF3 (batch mode)
[048] Diazotization (when using recovered BF3):
Charged aniline (50.0 g, 0.53 moles, 1.0 eq) into the RBF at 25 - 30 ° C under stirring and cooled the mass to 10 ± 5 °C. Con. Hydrochloric acid (97 g, 35 – 36% solution in water) was added dropwise over a period of 10 -15 min by maintaining the temperature at 10 ± 5 °C. Aqueous solution of Sodium tetrafluoroborate (73g, 0.31 moles) (corresponding to recovered BF3 from decomposition reaction) and freshly prepared tetrafluoroboric acid solution (62.75 g, 0.23 moles) was added dropwise over a period of 10 -15 min by maintaining the reaction mass temperature at 10 ± 5 °C. Further the mass was cooled to (-5) ± 5 °C and a solution of sodium nitrite (38.84 g of NaNO2, 1.05 eq in 50.0 mL water) was added dropwise over a period of 1 -2 hr by maintaining the temperature at (-5) ± 5 °C. Stirred the reaction mass at (-5) ± 5 °C for 30 – 45 min. Filtered the reaction mass, washed the bed with chilled methanol (2 x 50 mL) followed by chilled Ortho dichlorobenzene (2 x 50 mL) to get diazonium tetrafluoroborate salt as off white to pale pink solid (125 g wet) with >98% purity by HPLC. This wet solid was decomposed and further purified by distillation to get 34.6 g (67 % yield over 2 steps) of Pure Fluorobenzene with >99% purity by GC.

Example 4
Synthesis of 1,4-difluorobenzene (batch mode)
[049] Diazotization: Charged 4-fluoroaniline (50.0 g, 1.0 eq) into the RBF at 25 - 30 ° C under stirring and cooled the mass to 10 ± 5 °C. Con. Hydrochloric acid (42.2 g, 0.9 eq, 35 – 36% solution in water) was added dropwise over a period of 10 -15 min by maintaining the temperature at 25 ± 5 °C. Freshly prepared tetrafluoroboric acid solution (103.2 g, 1.3 eq, freshly prepared solution) was added dropwise over a period of 10 -15 min by maintaining the reaction mass temperature at 25 ± 5 °C. Further the mass was cooled to (-5) ± 5 °C and a solution of sodium nitrite (32.55 g of NaNO2, 1.05 eq in 50.0 mL water) was added dropwise over a period of 1 -2 hr by maintaining the temperature at (-5) ± 5 °C. Stir the reaction mass at (-5) ± 5 °C for 30 – 45 min. Filter the reaction mass, wash the bed with chilled 1:1 IPA:ODCB mixture (2 x 50 mL) followed by Ortho dichlorobenzene (2 x 50 mL) to get diazonium tetrafluoroborate salt as off white solid (96.8 g wet) with >98% purity by HPLC. HBF4 solution was freshly prepared as mentioned above.
[050] Decomposition: Charged ODCB (150 mL) and diazonium tetrafluoroborate (24.2 g, lot-1) into the RBF at 25 - 30 ° C under stirring. Slowly heated the reaction mass to 110 ± 3 °C with stirring till the BF3 evolution stopped. Cooled the reaction mass to below 40 °C and added diazonium tetrafluoroborate (24.2 g, lot-2). Slowly heated the reaction mass to 110 ± 3 °C till the BF3 evaluation stopped. Cooled the reaction mass to below 40 °C and added diazonium tetrafluoroborate (24.2 g, lot-3). Slowly heated the reaction mass to 110 ± 3 °C till the BF3 evaluation stopped. Cooled the reaction mass to below 40 °C and added diazonium tetrafluoroborate (24.2 g, lot-4). Slowly heated the reaction mass to 110 ± 3 °C till the BF3 evaluation stopped. Heated the reaction mass further to 130 ± 3 °C to ensure the complete decomposition and stirred the mass for 30 – 40 min. Cooled the reaction mass to 25 ± 5 °C, added water (300.0 mL) and separated the layers. The organic layer was distilled to get pure 1,4-difluorobenzene with >99% purity by GC (34.85 g, 67.9% yield over 2 steps).
Example 5
Synthesis of 1-fluoronaphthalene (batch mode)
[051] Diazotization: Charged 1-Naphthylamine (50.0 g, 1.0 eq) into the RBF at 25 - 30 ° C under stirring. Con. Hydrochloric acid (43.63 g, 1.2 eq, 35 – 36% solution in water) was added dropwise over a period of 10 -15 min by maintaining the temperature at 25 ± 5 °C. The reaction mass was heated to 65 ± 3 °C and maintained at same temperature for 30 – 45 min. Freshly prepared tetrafluoroboric acid solution (100.6 g, 1.1 eq, freshly prepared solution) was added dropwise over a period of 10 -15 min by maintaining the reaction mass temperature at 25 ± 5 °C. Further the mass was cooled to 3 ± 2 °C and a solution of sodium nitrite (25.26 g of NaNO2, 1.05 eq in 50.0 mL water) was added dropwise over a period of 1 -2 hr by maintaining the temperature at (-3 ± 2 °C. Stir the reaction mass at 3 ± 2 °C for 30 – 45 min. Filtered the reaction mass, washed the bed with chilled IPA (2 x 50 mL) followed by n-heptane (2 x 50 mL) to get diazonium tetrafluoroborate salt as brown solid which was air dried for 24 h to get 77.4 g with >96% purity by HPLC. HBF4 solution was freshly prepared as mentioned above.
[052] Decomposition: Charged n-heptane (400 mL) and heated the mass to 63 ± 2 °C under stirring. Charged diazonium tetrafluoroborate (19.35 g, lot-1) into the RBF at 63 ± 2 °C. Slowly heated the reaction mass to 72 ± 3 °C till the BF3 evolution stopped. Diazonium tetrafluoroborate (19.35 g, lot-2) was added and continued the reaction till the BF3 evaluation stopped. Diazonium tetrafluoroborate (19.35 g, lot-3) was added and continued the reaction till the BF3 evaluation stopped. Diazonium tetrafluoroborate (19.35 g, lot-4) was added and continued the reaction till the BF3 evaluation stopped. Heated the reaction mass further to 82 ± 3 °C to ensure the complete decomposition and stirred the mass for 2h. Cooled the reaction mass to 25 ± 5 °C, purged nitrogen gas into the mass to remove residual boron trifluoride gas. Further the mass was distilled to get pure 1-fluoronaphthalene with >99% purity by GC (32.84 g, 64.4% yield over 2 steps).
Example 6
Continuous process of producing aryl fluoride(Fluorobenzene)
[053] The procedure for fluorodiazotization and subsequent decomposition to obtain aryl fluorides includes two feeds, Feed-1 contains Aniline (aryl amine) (1eq), Hydrochloric acid HCl (1.8eq), Fluoroboric acid (HBF4) (1.72 eq), which becomes a thick white slurry when prepared under 20⁰C. This slurry is diluted in with 8eq water to make a homogeneous solution and the reaction was performed in a glass static mixer 8 ml volume reactor with no utility during reaction with sodium nitrite solution(1.05eq) in water (12.6% soln.) as Feed-2 at -5⁰C to 5⁰C in the product collection vessel, from here the product was taken to filtration to separate the diazonium salt, which was then made into a slurry by using ODCB as solvent in decomposition in a 1/8” coil reactor dipped in 120oC Oil bath followed by instant chilling 1/8” coil at 0⁰C to obtain Fluorobenzene (aryl fluoride).(not claimed in the invention)
Example 7
[054] To avoid solidification inside the reactor in Reaction 1 and make the reaction mixture flowable at lower temperatures, a helical coil reactor made of Inconel metal for achieving better heat transfer was employed in which the flow came from bottom turn to the top turn. Experiments are performed in this helical reactor to carry out diazotization step with includes two feeds, Feed-1 contains aryl amine (Aniline) (1eq), Hydrochloric acid HCl(1.8eq), Fluoroboric acid (HBF4) (1.72eq), which becomes a thick white slurry when prepared under 20⁰C. This slurry was diluted with 8eq water to make a homogeneous solution and the reaction was performed residence times to as low as 10 secs. The reaction could be performed at temperatures as low as 10⁰C in the utility side and the salt yields were observed lower (85% yield on wet basis) (not claimed in the invention)
[055] The Helical reactor design worked well during lab scale development and when scaled up, choking in the helical reactor (Inconel) is observed, that might be due to the longer residence time at -6⁰C and the same is tried with lower residence -times which gave lower yields.
Example 8
Step-II reaction of Decomposition in an Expanded tube reactor(procedure)
[056] Step-II reaction of decomposition of the aryldiazonium tetrafluoroborate is done in the Expanded tube reactor (ETR). The ETR is a hollow 1-inch tube followed by a 2-inch tube with utility and a half inch outlet for liquid in the bottom end and a 1-inch outlet for gas at the top end. The ETR is aligned in such a way that at low flow rate (16-17ml/min), the residence time is maintained around 1 minute which gave enough time to increase the temperature of the slurry from room temperature to 80-85⁰C with the utility temperature of 111-120⁰C. It is followed by two condensers on product vessel to minimize the aryl fluoride loss at -15⁰C to-20⁰C which caused continuous decomposition and the vacant tube space ensured the gas evolution from the top side that didn’t interfere with the liquid flow.

Example 9
Continuous process of producing aryl fluoride in flow reactor SSCR followed by Flow reactor ETR: Preparation of Fluorobenzene
Fluorodiazotization in SSCR
[057] Feed 1 contains Aniline(1eq), Hydrochloric acid (HCl)(1eq), Fluoroboric acid (HBF4) (1.1eq) which becomes a thick white slurry when prepared under 20⁰C after addition, under continuous mixing. This slurry is diluted with ODCB (6eq) and is reacted with sodium nitrite solution(1.05eq) in 2 volumes of water (Feed 2) in respect of the starting material. The invention has been performed at both 500g and 300g scale continuously with repeatability in flow with 98%+ salt purity and 88-95% yield by weight in a Scrapped surface continuous reactor (SSCR) and the wet salt is filtered and washed with appropriate solvent to remove water.
Decomposition in ETR
[058] The wet salt obtained from the SSCR is made into a slurry again by adding 5 volumes of ODCB and decomposition of the same is done with a residence time of 80 secs in an expanding tube reactor (ETR) with utility temperature maintained at 111 to 120οC. The reaction mass containing ODCB and product fluorobenzene is collected in an 10L stirred tank with 2 condensers connected on the top before vent line which was maintained at -18 to -20οC to minimize the fluorobenzene losses, with residence times of 25 mins for reaction 1 and 1 min 20 seconds for reaction 2 giving an overall yield of 58-60% in both steps. The Scrapped surface continuous reactor (SSCR) could easily handle the slurry as feed to the step 1 along with sodium nitrite solution. Continuous flow of the slurry through the outlet is ensured when the temperature is maintained at the desired temperature range of -8⁰C to +4⁰C.
[059] Those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for designing other products without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the claims are not to be limited to the specific examples depicted herein. For example, the features of one example disclosed above can be used with the features of another example.
[060] Furthermore, various modifications and rearrangements of the parts may be made without departing from the spirit and scope of the underlying inventive concept. For example, the geometric configurations disclosed herein may be altered depending upon the application, as may be the material selection for the components. Thus, the details of these components as set forth in the above-described examples, should not limit the scope of the claims.

ADVANTAGES OF THE INVENTION
[061] The invention provides an efficient process for the synthesis of aryl fluorides from water free diazonium tetrafluoroborate salt followed by decomposition of the diazonium tetrafluoroborate salt without drying it. Additionally, it provides an efficient recovery or absorption technology for the by-product boron trifluoride and re-using the same to make the process economical. Additionally, the instant invention has the following advantages:
1. The suitable ratio of tetrafluoroboric acid, Hydrochloric acid, Sodium nitrite and water is achieved which made the process cost effective.
2. Usage of alcoholic solvents to remove water effectively from Aryldiazonium Tetrafluoroborate salt could avoid the formation of corresponding alcohol impurity during decomposition.
3. Suitable solvent system was arrived at for the decomposition of Aryldiazonium Tetrafluoroborate to get better yields.
4. Recovery of boron trifluoride (side product) as Sodium tetrafluoroborate from the decomposition of Aryldiazonium Tetrafluoroborate using Sodium fluoride in water and recycling of recovered Sodium tetrafluoroborate to synthesize Aryldiazonium Tetrafluoroborate made the process not only cost-effective but also eco-friendly.

ANALYSIS OF NOVELTY, INVENTIVE-STEP AND UTILITY OF THE INVENTION
[059] The instant invention titled “Improved process for the preparation of aryldiazonium tetrafluoroborates and subsequent conversion to aryl fluorides” is novel in the light of the prior art as it employs the aryldiazonium tetraborate salt produced by the known Balz-Schiemann reaction making it water-free by washing with suitable solvents such as polar-protic, polar-aprotic solvents and employs the aryldiazonium tetraborate salt as a wet cake without drying it in the decomposition step to obtain aryl fluorides. The decomposition of the aryldiazonium tetraborate salt in the form of wet cake is done after dissolving it in polar, non-polar aprotic solvents for controlled decomposition under milder temperature conditions. The instant invention has inventiveness since it provides an effective method for obtaining aryl fluorides from aryl amines and heteroaryl amines (having at least one -NH2 moiety) wherein the liberated BF3 is effectively recycled to the reaction mixture on dissolving in NaF/KF or water in both batch and continuous modes. The instant invention has excellent utility value since it provides an improved process for synthesizing aryl fluorides that find extensive application in pharmaceuticals and agricultural operations.
, Claims:I/We claim:
1. A method of preparation of aryl fluorides of the formula Ar-X from aryldiazonium tetrafluoroborates synthesized from compounds of the structure Ar-NH2, wherein Ar-NH2 is any substituted or un-substituted aryl (containing mono, polycyclic aromatic nucleus ) or substituted or unsubstituted heteroaryl compound containing at least one -NH2 group, using a fluorinating species and decomposition of the anhydrous aryldiazonium tetrafluoroborate without prior drying, to yield compounds of the structure Ar-X, wherein Ar-X is any aryl (containing mono, polycyclic aromatic nucleus) or heteroaryl fluoride containing at least one-F moiety, in a batch or continuous mode wherein the method comprises the steps of;
a) Step I of Fluorodiazotization involving the oxidation of Ar-NH2 using nitrous acid followed by salt formation with a fluorinating species to form aryldiazonium tetrafluoroborate, which is filtered, washed with a suitable solvent to make it water-free and is obtained as a wet cake,
b) Step II of Decomposition of the aryldiazonium tetrafluoroborate that is obtained as a water-free wet cake from the fluorodiazotization step, involving replacing the diazonium part (-N2) from aryl diazonium tetrafluoroborate salt with fluorine by thermal decomposition.
2. The fluorodiazotization as claimed in claim 1 employs water as a solvent preferably wherein the ratio of solvent to Ar-NH2 is 0 to 5 V.
3. The fluorinating species as claimed in claim1 is selected from a group comprising of aqueous solution of tetrafluoroboric acid (HBF4), Sodium tetrafluoroborate (NaBF4), combination of aqueous tetrafluoroboric acid (HBF4) and recovered aqueous Sodium tetrafluoroborate (NaBF4) and more preferably from aqueous solution of tetrafluoroboric acid.
4. The tetrafluoroboric acid as claimed in claim 3 is generally prepared in-situ by the reaction of aqueous Hydrofluoric acid and Boric acid wherein the molar ratio of aqueous HF to Boric acid is 4 to 6 and more preferably in the ratio of 4.4:5.2.
5. The method as claimed in claim 1 wherein the amount of tetrafluoroboric acid to Ar-NH2 is in 1 to 1.5 molar ratio, and more preferably in 1 to 1.3 molar ratio.
6. The continuous mode as claimed in claim 1 is carried out in 2 steps, for producing aryl fluorides from aryldiazonium tetrafluoroborates using two flow reactors namely, Scrapped surface continuous reactor (SSCR) as reactor 1 and an expandable tube reactor (ETR) as reactor 2, wherein;
a) The step -I reaction comprises of fluorodiazotization of Ar-NH2 is accomplished in flow reactor 1 to obtain aryl diazonium tetrafluoroborate salt which is filtered and washed with a suitable solvent to make it water-free and obtain in the form of a wet cake,
b) Step-II reaction comprises of the decomposition of the water-free salt obtained in step-I in the form of a wet cake continuously in flow reactor 2, wherein the continuous flow of the salt as a slurry is ensured by dissolving the step-I product in a suitable solvent followed by gradual heating to obtain Ar-X along with the recovery of the two gases nitrogen and boron trifluoride ( BF3).

7. The suitable solvent as claimed in claim 6 and claim 1 is selected from a group comprising of organic polar protic solvents (alcoholic solvents) like methanol, ethanol, isopropyl alcohol or the mixture of polar protic solvents (alcoholic solvents) like methanol or ethanol or isopropyl alcohol and non-polar aprotic solvents, halogenated or nonhalogenated aliphatic solvents or aromatic hydrocarbons, nitrobenzene, chlorobenzene, 1,2-dichlorobenzene, Xylenes, toluene, n-heptane and ortho-dichlorobenzene (ODCB) and more preferably ortho -dichlorobenzene or n-heptane wherein the ratio of solvent to the aryldiazonium tetra fluoroborate is 2-6 V /V.
8. The strength of the aqueous solution of hydrofluoric acid as claimed in claim 4 is 40% w/w.
9. The freshly prepared tetrafluoroboric acid as claimed in claim 4 is having a strength of 33 to 57% w/w in water and preferably having a strength of 33% w/w in water.
10. The recovered Sodium tetrafluoroborate (NaBF4) solution as claimed in claim 3 is an aqueous solution of BF3 that has been recovered from the decomposition step wherein, the strength of the solution is 33 to 57% w/w.
11. The decomposition as claimed in claim 1 is done at a temperature of 50 °C to 150 °C and preferably at 60 °C to 130 °C.
12. The recovery of boron trifluoride as claimed in claim 6 from the decomposition of diazonium tetrafluoride was by purging the liberated boron trifluoride gas into an inorganic acid such as hydrofluoride or a metal fluoride such as Sodium fluoride or Potassium fluoride in water and more preferably into Sodium fluoride in water.
13. The recovery of boron trifluoride as claimed in claim 12 is by purging the liberated boron trifluoride gas into Sodium fluoride in water wherein the ratio of water to sodium fluoride is 1.5 – 4 by volume and preferably the ratio is 1: 2 by volume.
14. The purging of boron trifluoride gas into the metal salts in water as claimed in claim 12 is performed at 20°C to 50 °C, preferably done at 25 ± 5 °C.
15. The method as claimed in claim 1 wherein the purification of the fluorinated product ‘Ar-X’ is performed by distillation at appropriate temperature with or without vacuum.
Dated the 13th August 2023