Aryl fluoride

By adding a concentrated solution of sodium borofluoride to a solution of a diazonium salt, the diazonium fluoborate is precipitated this decomposes into the aryl fluoride when cautiously heated, for example ... 

Chlorination is carried out m a manner similar to brommation and provides a ready route to chlorobenzene and related aryl chlorides Fluormation and lodmation of benzene and other arenes are rarely performed Fluorine is so reactive that its reaction with ben zene is difficult to control lodmation is very slow and has an unfavorable equilibrium constant Syntheses of aryl fluorides and aryl iodides are normally carried out by way of functional group transformations of arylammes these reactions will be described m Chapter 22... 

Diazonium salt chemistry provides the principal synthetic method for the prepara tion of aryl fluorides through a process known as the Schiemann reaction In this pro cedure the aryl diazonium ion is isolated as its fluoroborate salt which then yields the desired aryl fluoride on being heated... 

Diazotization of an arylamine followed by treatment with fluoroboric acid gives an aryl diazonium fluoroborate salt Heating this salt converts it to an aryl fluoride... 

Formation of aryl Grignard reagents (Section 14 4) Aryl halides react with magnesium to form the corresponding arylmagnesium halide Aryl iodides are the most reac tive aryl fluorides the least A similar reaction occurs with lithium to give aryllithium reagents (Section 14 3)... 

In contrast to nucleophilic substitution m alkyl halides where alkyl fluorides are exceedingly unreactive aryl fluorides undergo nucleophilic substitution readily when the ring bears an o or a p nitro group... 

Aromatic Ring Fluorination. The formation of an aryl diazonium fluoride salt, followed by decomposition, is a classical reaction (the Schiemaim reaction) for aryl fluoride preparation (21). This method has been adapted to the production-scale manufacture of fluorobenzene [462-06-6]... 

The Balz-Schiemaim reaction is a useful laboratory and industrial method for the preparation of fluoroaromatics. The water-insoluble diazonium fluoroborate is filtered, dried, and thermally decomposed to give the aryl fluoride, nitrogen, and boron trifluoride (28—30). 

This represents the first large-scale appHcation of a fluoroaryl organometaOic. Other silicon-containing aryl fluorides such as pentafluorophenyldimethyl silanes, CgF Si(CH2)2X (X = Cl NH2 N(0211 )2), are offered commercially as Flophemsyl reagents for derivati2ation of sterols in chromatographic analysis (166). 

Other less widely used alternative diazonium salts for aryl fluoride synthesis include arenediazonium hexafluoroantimonates, ArN2SbFg, arenediazonium hexafluoroarsonates, ArN AsFg, and arenediazonium hexafluorosilicates, (ArNjljSiFg 114]... 

Depending on structure, photolysis of films of arenediazonium fluoroborates and hexafluorophosphates at room temperature gives aryl fluorides m 10-75% yield [32] In situ photochemical decomposition of arenediazonium fluoroborates... 

A recently discovered variant of the Wallach technique is the silver ion cata lyzed fluorination of aryl diazo sulfides in hydrogen fluonde-pyridine-toluene solvent [57] (equation 12) Electron withdrawing substituents such as acetyl give higher yields of aryl fluoride (71%) than electron donating groups (butyl 39%, methoxy, 2-14%), reductive dediazoniation competes with fluorination... 

The efficacy of ring fluorination depends on the nature and position of the activating group, Y, m the aromatic ring The relative extent of for N (CH3)3 displacement decreases in the following order for Y p-NOy (71%), p-CN (24%), P-CH3CO (15%), p CHO (<5%) = m NO2 (<5%) This fluorodequaternization technique was subsequently adapted to prepare numerous NC A (no-camer-added) F-labeled aryl fluorides [7J, 74]... 

Aromatic fluorodenitration was first discovered in the reaction of polychloro-nitrobenzenes with potassium fluoride, when 2,3,5,6-tetrachlorofluorobenzene was prepared in 37% yield from 2,3,5,6-tetrachloronitrobenzene 105] The technique has been adapted to prepare aryl fluorides from other activated nitro aromatics for applications in pharmaceutical and polymer chemistry (equation 31) Fluorodenitration also has been applied to prepare radiolabeled ( F) fluo-roaromatics [74, 106]... 

A characteristic feature of aromatic fluorodenitration is modest yield due to side reactions promoted by potassium nitrite and/or its decomposition product, potassium oxide, with the aryl fluoride or starting material... 

The use of phthaloyl dichlonde as a scavenger for potassium nitrite and/or potassium oxide [108, 109, III] significantly increases yields of aryl fluorides, m fluoronitrobenzene is obtained in 70% yield with sulfolane as a solvent at 200 °C after 72 h Addition of tetraphenylphosphonium bromide as a phase-transfer catalyst to the phthaloyl dichlonde scavenger system further increases the yield of m-fluoronitrobenzene to 89% under less forcing conditions 150-180 C, 5 h) [if 2] This optimized technique can be applied to give m-fluorobenzonitnle from in-m-trobenzonitnle in 86% yield [/i2]... 

Potassium nitrite by-product can react with nitroaromatic substrate to suppress yields of aryl fluorides Modest yields (40-60%) of fluorophthafic anhydride are obtained from 3- or 4-nitiophthalic anhydride and potassium fluonde due to formation of by-product dipotassium salt of 3- or 4-nitrophtlialic acid [1/3,114, 115] (equation 33) Higher yields (93%) of 3-fluorophfhalic anhydride can be realized by regenera tion of 3-nitrophthalic anhydride from the dipotassium salt with thionyl chloride, followed by addition of fresh potassium fluoride [7/5] (equation 33)... 

Reduction of aryl fluorides by vanous reagents to hydro denvatives was also treated extensively m reference 12 A httle used method, electrochemical reduction, defluonnates simple aryl fluondes [19, 20] (equations 13 and 14)... 

Preparation of aryl fluorides Addition of fluoroboric acid to a solution of a diazonium salt causes the precipitation of an aryl diazonium fluoroborate. When the dry aryl diazonium fluoroborate is heated, an aryl fluoride results. This is the Schiemann reaction it is the most general method for the preparation of aryl fluorides. 

Leaving-group effects Because aryl fluorides have the strongest carbon-halogen... 

Schiemann reaction (Section 22.17) Preparation of an aryl fluoride by heating the diazonium fluoroborate formed by addition of tetrafluoroboric acid (HBF4) to a diazonium ion. 

The preparation of an aryl fluoride—e.g. fluorobenzene 3—starting from an aryl amine—e.g. aniline 1—via an intermediate arenediazonium tetrafluoroborate 2, is called the Schiemann reaction (also called the Balz-Schiemann reaction) The diazotization of aniline 1 in the presence of tetrafluoroborate leads to formation of a benzenediazonium tetrafluoroborate 2 that can be converted into fluorobenzene 3 by thermolysis. 

Problem 16.17 1 The herbicide oxyfluorfen can be prepared by reaction between a phenol and an aryl fluoride. Propose a mechanism. 

The methanol-ether filtrate has a slight yellow color. It is not known what impurity is removed by this solvent pair. However, the submitters found that this treatment improved the yield of several aryl fluorides prepared according to the present procedure. 

This procedure is a general way of converting arylamines to aryl fluorides, for it has been used to make fifteen other aryl fluorides. It generally gives better yields than the Schiemann reaction. 

Aryl iodides and fluorides can be prepared from arylthallium bis(trifluor-oacetates) (see 12-21), indirectly achieving the conversions ArH —> Arl and ArH ArF. The bis(trifluoroacetates) react with KI to give Arl in high yields. Aryllead triacetates, ArPb(OAc)3, can be converted to aryl fluorides by treatment with BFs-etherate. ... 

The ease of dehalogenation of C H X by Ni(ll)/ IMes HCl 1/NaO Pr decreased in the order 1 > Br > Cl F. Subsequent work showed that a 1 1 combination of Ni and NHC in the presence of NaOCHEt resulted in enhanced reactivity towards aryl fluorides [6], Again, the A-mesityl substituted ligand IMes HCl 1 imparted the highest level of catalytic activity. Table 8.2 illustrates that hydrodefluorination is sensitive to both the nature of the substituents on the aromatic ring and the specific regioisomer. Thus, 2- or 4-fluorotoluene (Table 8.2, entry 2) proceeded to only 30% conversion after 15 h, whereas quantitative conversion of 2-fluoroanisole (Table 8.2, entry 3) and high conversion of 3-fluoropyridine (Table 8.2, entry 5) was achieved in only 2-3.5 h. The reactivity of 2-fluoropyridine was compromised by more efficient nucleophilic aromatic substitution. 

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