Friedel Crafts with boron trifluoride

Ethynylcarbazole was apparently formed by sodamide treatment of 9-dichlorovinylcarbazole (97) and zinc reduction of 97 gave 98. Where no reaction occurred with the Z isomer, 99 gave the dimer 100 with boron trifluoride the process presumably involves Lewis acid-catalyzed alkylation of one double bond by another double bond, complexed to boron trifluoride, followed by intramolecular Friedel-Crafts type alkylation at the carbazole 1-position. ... 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

The Friedel-Crafts acetylation of 3-phenylsydnone was accomplished with boron trifluoride etherate as catalyst. Formylation at C-4 by the Vilsmeier procedure occurred with 3-phenylsydnone. Mercuration is easily afforded with mercury(II) acetate or mer-cury(13) chloride and thioethers can be made directly with DMSO in acetyl chloride (74T409). At least one fused ring as in compound (35) has been made by a coupling reaction on the sydnone (34) at C-4 (79JCS(P2)175l). 

Methods for the synthesis of hop bitter acids are due to the elegant work of RiedI (78-84). The substrates are phloracylphenones, which are readily available from condensation of phoroglucinol with acid chlorides (Friedel-Crafts synthesis), nitriles (Hoesch synthesis) or carboxylic acids with boron trifluoride as catalyst. Carbon acylation of a phloracylphenone can give one monoalkylated derivative (13, Fig. 13), two dialkylated derivatives (14 and 15) and one tri- or tetra-alkylated derivative (16 and 17, respectively). The possibility of oxygen acylation can not be excluded. 

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. 

Cationic polymerization of coal-tar fractions has been commercially achieved through the use of strong protic acids, as well as various Lewis acids. Sulfuric acid was the first polymerization catalyst (11). More recent technology has focused on the Friedel-Crafts polymerization of coal fractions to yield resins with higher softening points and better color. Typical Lewis acid catalysts used in these processes are aluminum chloride, boron trifluoride, and various boron trifluoride complexes (12). Cmde feedstocks typically contain 25—75% reactive components and may be refined prior to polymerization (eg, acid or alkali treatment) to remove sulfur and other undesired components. Table 1 illustrates the typical components found in coal-tar fractions and their corresponding properties. 

Catalysts used in the polymerization of C-5 diolefins and olefins, and monovinyl aromatic monomers, foUow closely with the systems used in the synthesis of aHphatic resins. Typical catalyst systems are AlCl, AIBr., AlCl —HCl—o-xylene complexes and sludges obtained from the Friedel-Crafts alkylation of benzene. Boron trifluoride and its complexes, as weU as TiCl and SnCl, have been found to result in lower yields and higher oligomer content in C-5 and aromatic modified C-5 polymerizations. 

Although all four tocopherols have been synthesized as their all-rac forms, the commercially significant form of tocopherol is i7//-n7i a-tocopheryl acetate. The commercial processes ia use are based on the work reported by several groups ia 1938 (15—17). These processes utilize a Friedel-Crafts-type condensation of 2,3,5-trimethylhydroquinone with either phytol (16), a phytyl haUde (7,16,17), or phytadiene (7). The principal synthesis (Fig. 3) ia current commercial use iavolves condensation of 2,3,5-trimethylhydroquiQone (13) with synthetic isophytol (14) ia an iaert solvent, such as benzene or hexane, with an acid catalyst, such as ziac chloride, boron trifluoride, or orthoboric acid/oxaUc acid (7,8,18) to give the all-rac-acetate ester (15b) by reaction with acetic anhydride. Purification of tocopheryl acetate is readily accompHshed by high vacuum molecular distillation and rectification (<1 mm Hg) to achieve the required USP standard. 

Alkylation of furan and thiophene has been effected with alkenes and catalysts such as phosphoric acid and boron trifluoride. In general, Friedel-Crafts alkylation of furans or thiophenes is not preparatively useful, partly because of polymerization by the catalyst and partly because of polyalkylation. 

Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesullonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143... 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

One synthetic route to lavandulyl acetate starts with prenyl acetate, which dimerizes in the presence of a Friedel-Crafts catalyst, such as boron trifluoride-diacetic acid [74]. 

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

In carrying out the alkylation of benzene the propylene tetramer is reacted with an excess of benzene in the presence of a Friedel-Crafts catalyst such as aluminum chloride, boron trifluoride, or hydrofluoric acid. With careful control of this reaction, yields of alkylate boiling from 500° to 650° F. are of the order of 80% of theory with the losses due to slight olefin degradation and dialkylation. Inspection of commercial aromatic products, believed to be typical of this process, indicates the composition to be that shown in... 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

Friedel-Crafts acylation of benzo[6]thiophene using a variety of catalysts gives a mixture of isomers, in which the 3-isomer predominates in a ratio of about 4 1. The milder catalysts, such as boron trifluoride etherate or iodine, give the best yields, since there is less destruction of the ring. While aluminum chloride gives the 3-isomer in about 9 1 ratio over the 2-isomer, the total yield is only 38%, as contrasted to yields over 70% with milder catalysts (70AHC(11)177). 

Friedel-Crafts acylation of even the kinetically stable acetylacetonates can only be carried out with difficulty and with the use of vigorous conditions. A mixture of boron trifluoride etherate... 

Sulfonation of aromatic compounds is generally carried out with sulfuric acid, halosulfuric acids, or sulfur trioxide as reagent with or without solvent.458,459 Friedel-Crafts catalysts such as aluminum chloride and boron trifluoride are effective catalysts in certain sulfonations with sulfuric acid and chlorosulfuric acid. 

Other interesting reactions with diketene include its use in a Friedel-Crafts-type acetoacetylation of ferrocene (Scheme 14) and a l,l -diphosphaferrocene <20010M4448>. When boron trifluoride was used as the Lewis acid, BF2 chelates of the acetoacetylated metallocenes were formed. 

A typical cationic polymerization is conducted with highly purified monomer free of moisture and residual alcohol, both of which act as inhibitors, in a suitably dry unreactive solvent such as toluene with a Friedel-Crafts catalyst, eg, boron trifluoride, aluminum trichloride, and stannic chloride. Usually low temperatures (—40 to — 70° C) are favored in order to prevent chain-transfer or sidereactions. 

The first step in the Friedel-Crafts synthesis is formation of an electrophile capable of electrophilic substitution in the aromatic ring. Such an electrophile (or cation) is generated from an alkyl halide by its reaction with a Lewis acid, in this case boron trifluoride. Boron trifluoride... 

Alcohols are another source of carbocations for Friedel-Crafts alkylations. Alcohols commonly form carbocations when treated with Lewis acids such as boron trifluoride (BF3). If benzene (or an activated benzene derivative) is present, substitution may occur. 

The application of the ideas of Lewis on acids, which correlate a wide range of phenomena in qualitative fashion, has as yet led to very few quantitative studies of reaction velocity but has led to detailed speculations as to mechanisms (Luder and Zuffanti, 118). Friedel-Crafts reactions are considered to be acid-catalyzed, the formation of a car-bonium ion being the first step. The carbonium ion then acts as an acid relative to the base benzene which, upon loss of a proton, yields the alkylated product. Isomerizations of isoparaffins can be explained in similar fashion (Schneider and Kennedy, 119). An alkyl halide yields a carbonium ion on reaction with acids such as boron trifluoride, aluminum chloride, and other metal halides. 

Lewis acids may also act as catalysts with an efficiency roughly parallel to that found in Friedel-Crafts and related reactions These rearrangements are first-order in acid and a substrate-acid adduct is believed to be rapidly formed which rearranges in a slow step with concomitant release of catalyst. Adducts of benzoyl azide with boron trichloride and trifluoride have been isolated at low temperatures... 

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