Alkyl fluorides Friedel-Crafts reactions

Much better results can be obtained with substituted aromatics. The reaction of aryl chloro- or fluoroformates which have alkyl groups in position 2 and 6 gives fluoroaromalic compounds in good yield. The Friedel-Crafts reaction is widely suppressed although Lewis acids or hydrogen fluoride are present in the reaction mixture. Another advantage of this process is that the fluoroaromalic compounds can be obtained from the fluoro- as well as from the chloroformates. which, in general, are easier to prepare, A typical example is the formation of 2-fluoro-1.3-dimethylbenzene (2). ... 

Alkylation of Aromatics. Aromatic hydrocarbons containing a replaceable hydrogen can be alkylated unless steric effects prevent introduction of the alkyl group (61,78-82). The reaction is called the Friedel-Crafts alkylation, first realized in the presence of aluminum chloride, which is the catalyst still the most frequently used and studied in Friedel-Crafts reactions. In addition, many other acid catalysts are effective (80,82-84). These include other Lewis acids (other aluminum halides, gallium chloride, boron trifluoride, ferric chloride, zinc chloride, stannous and stannic chloride, antimony chloride) and protic acids (hydrogen fluoride, concentrated sulfuric acid, phosphoric acid, polyphosphoric acid, trifluo-romethanesulfonic acid, and alkane- and arenesulfonic acids). 

Woolhouse, R.A. and Eastham, A.M. (1966) Co-catalysis in Friedel-Crafts reactions. X. Interaction between boron tiifluoride and alkyl fluorides. J. Chem. Soc. B, 33-36. 

The mechanisms of Friedel-Crafts reactions have been studied extensively. The alkylations involve the use of olefins, alkyl halides, alcohols, ethers, and esters. The acylations make use of acids, esters, acid halides, and acid anhydrides. This type of reaction is acid-catalyzed, using such compounds as boron, aluminum, iron, tin, and other metallic halides, as well as sulfuric acid, phosphorus pentoxide, orthophosphoric acid, and hydrogen fluoride. These act as acids in the catalytic activity described because they all have a strong tendency to accept a share in an electron pair as the first step in the reaction. 

Other catalysts which may be used in the Friedel - Crafts alkylation reaction include ferric chloride, antimony pentachloride, zirconium tetrachloride, boron trifluoride, zinc chloride and hydrogen fluoride but these are generally not so effective in academic laboratories. The alkylating agents include alkyl halides, alcohols and olefines. 

Concerning my research during my Dow years, as I discuss iu Chapter 4, my search for cationic carbon intermediates started back in Hungary, while 1 was studying Friedel-Crafts-type reactions with acyl and subsequently alkyl fluorides catalyzed by boron trifluoride. In the course of these studies I observed (and, in some cases, isolated) intermediate complexes of either donor-acceptor or ionic nature. 

Inflates of aluminum, gallium and boron, which are readily available by the reaction of the corresponding chlorides with triflic acid, are effective Friedel-Crafts catalysts for alkylation and acylation of aromatic compounds [119, 120] Thus alkylation of toluene with various alkyl halides in the presence of these catalysts proceeds rapidly at room temperature 111 methylene chloride or ni-tromethane Favorable properties of the Inflates in comparison with the correspond 1 ng fluorides or chlorides are considerably decreased volatility and higher catalytic activity [120]... 

Lewis acids such as boron trihalides will also form stronger bonds with fluoride than with the other halogens, and can be used to abstract fluoride selectively from halogenated compounds. Some examples of Friedel-Crafts alkylations with fluoro-haloalkanes in which only fluoride is displaced are sketched in Scheme 4.14. As shown by the last example, however, hydride migrations can readily occur under such strongly acidic reaction conditions. 

Friedel-Crafts alkylation has been used in an important synthesis of aryl C-glycosides, which are potent anti-tumor agents, from glycosyl fluorides (equation 99)65 661. The reaction takes place rapidly in dichloromethane, at room temperature using a novel zirconium complex and silver perchlorate combination catalyst. A similar alkylation has been performed by replacing the aromatic compound with either a silyl enol ether or an allylic compound using silver triflate as the catalyst662,663. 

Because of their Lewis acidity, the MX5 species, usually the fluorides or the chlorides, can act as catalysts in cyclotrimerizing or linearly polymerizing acetylenes (although in the latter case metal alkylidene intermediates may be important) and in Friedel-Crafts and related alkylation reactions. They also polymerize THF and can catalyze the hydrolysis of acetonitrile.21... 

Cleavage of a carbon-fluorine bond can be induced by reaction with a Lewis acid (see Chapter 4, Section VIC). In Friedel-Crafts alkylations, aUcyl fluorides are more reactive than the chlorides [37] with, for example, aluminium halides or boron halides as catalysts (Figure 5.17). 

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