Amines Schiemann reaction

This reaction is commonly achieved by diazotization of the amine in fluoro-boric acid, followed by decomposition of the diazonium salt (Schiemann reaction).Thus, l-amino-4-methylestra-l,3,5(10)-trien-17-one (50) is converted to the fluoro derivative (51) in 29% yield. The synthesis of 3-fluoroestra-l,3,5(10)-triene-17-one (55) from estrone proceeds via (52) and (53)... 

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. 

The Schiemann reaction seems to be the best method for the selective introduction of a fluorine substituent onto an aromatic ring. The reaction works with many aromatic amines, including condensed aromatic amines. It is however of limited synthetic importance, since the yield usually decreases with additional substituents present at the aromatic ring. 

Milner (1992) recently described a novel and versatile modification of the Balz-Schiemann reaction. The amine is diazotized with solid nitrosonium tetrafluoro-borate in CH2C12 and, without isolation, the diazonium salt is heated and yields the fluoroarene in good yield. The method is also applicable to aniline derivatives bearing carboxy and hydroxy substituents, compounds which give poor yields in the classical procedure. 

Due to the corrosive and toxic nature of volatile hydrogen fluoride, the fluorodediazoniation of aromatic and heteroaromatic amines in anhydrous hydrogen fluoride (see Section 26.1.2.), though very efficient, inexpensive and easy to scale up, needs special apparatus and safety measures which are not always available in every laboratory. Thus, the Balz-Schiemann reaction remains the most popular way to substitute aromatic amino groups for fluorine on a laboratory scale. Moreover, special techniques have been developed during the last decade to control formation, storage and decomposition of arenediazonium tetrafluoroborates on a large scale. 

Aromatic fluorination chemistry has a remarkably long history, and the first successful synthesis of aryl C-F bonds was reported in 1870 [22], Significant developments in the area in the early part of the 20th century included the discovery of Balz-Schiemann reaction [23,24] involving diazotization of an aromatic amine in the presence of tetrafluoroboric acid and the reaction scheme is shown in Fig. 4. The above reaction produces large quantities of waste (such as NaBF4,... 

Since volatile, anhydrous hydrogen fluoride is extremely corrosive and toxic, the fluorodediazo-niatron of aromatic amines with this agent require.s special apparatus and. safety conditions, which are not available in most laboratories. Thus, the decomposition of diazonium tclra-fliioro bo rates, which can be readily prepared from aromatic amines and casier-to-handle tetra-fluoroboric acid, is the commonest fluorodediazoniation process, usually referred to as the Balz-Schiemann reaction (see Vol. E 10a, p 705IT). 

An example of a thermal Balz-Schiemann reaction at room temperature is the preparation of the elusive 4-fluoropyridine (6) from pyridin-4-amine (5). ... 

The thermal Balz-Schiemann reaction has been used for the preparation of many fluoroaro-malic compounds from the corresponding amines, such as the anticancer agent 10, the es-trogen-sulfoconjugation inhibitor the asymmetric acceptor monofluorotetracyano-... 

Difunctional compounds, including certain halogenated ethers, aldehydes, ketones, phenols, amines, and nitro compounds, have been prepared by the Sandmeyer reaction. However, fluorophenols and fluoro acids are best obtained from the corresponding ethers and esters, respectively, which have been fluorinated by the Schiemann reaction. ... 

Fluoroquinoxaline has been prepared in 30% yield from quinoxa in-2-amine with 40% tetrafluoroboric acid (Balz-Schiemann reaction). 

Fluoropurin-8-amine nucleosides have also been prepared by appropriate modification of the Schiemann reaction, e.g. formation of 4. ... 

The synthesis of 7-azaindoles is a challenging task and there are few efficient routes to substituted derivatives. In the laboratory of C. Thibault, the concise and efficient synthesis of 4-fluoro-1/-/-pyrrolo[2,3-jb]pyridine was achieved. The fluorination was carried out using the Balz-Schiemann reaction. The aromatic amine precursor was prepared via the Buchwald-Hartwig coupling of the aryl chloride with A/-allylamine followed by deallylation. The diazonium tetrafluoroborate intermediate was generated at 0 C and it decomposed spontaneously in 48% HBF4 solution to afford the desired aromatic fluoride. 

Schiemann reaction. Formation of diazonium fluoborates by diazotization of aromatic amines in the presence of fluoborates, followed by their thermal decomposition to aryl fluorides. 

The Balz-Schiemann reaction for the introduction of fluorine into an aromatic nucleus involves forming the amine, then the diazonium fluoborate, which in turn decomposes into an aromatic fluoride (104,106,107). One of the reviews (104) of this reaction gives tables of the compounds prepared by this method. 

The Balz-Schiemann reaction, the classic synthesis of fluoro-aromatic compounds, involves diazotisation of an aromatic amine, isolation of the diazonium fluoroborate or hexafluorophosphate, then thermal decomposition of the dry salt, usually diluted with sand for safety. It is a useful method, with application to a number of heterocyclic systems, for example methyl 3-aminothiophene-2-carboxylate. ... 

The process most widely used for introducing fluorine into an aromatic nucleus is thermal decomposition of diazonium fluoroborates (Schiemann reaction) lc,1242 1244 these salts are usually very stable, even towards deflagration. They are precipitated (i) on addition of hydrogen tetrafluoroborate or NaBF4 to a diazonium solution obtained as usual from the amine in hydrochloric acid or (ii) on diazotization of the amine in HBF4 solution by aqueous... 

The Baltz-Schiemann reaction is the most often used method for the synthesis of 3-fluoropyridines. This method utilizes readily accessible 3-nitropyridines as the precursors, since they can be readily reduced into amines and then used in the Baltz-Schiemann reaction. In this section, selected examples applied for the synthesis of practically important compounds are given. For example, the Baltz-Schiemann reaction was used for the synthesis of fluoro-substituted epibatidine analogue 79 (epibatidine is a high-affinity nonselective ligand for nicotinic cholinergic receptor (nAChRs)) (Scheme 6.27). 

The Schiemann reaction is the most common method for the introduction of fluorine onto an aromatic ring. It is carried out by treatment of a primary aromatic amine with sodium nitrite in aqueous HCl followed by addition of HBF or NaBF. The diazonium fluoroborate salt precipitates and is collected and dried. Heating the dry salt brings about its decomposition to an aryl fluoride, nitrogen, and boron trifluoride. The Schiemann reaction is also thought to involve an aryl cation intermediate. 

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