Friedel-Crafts reactions boron trifluoride etherate

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 . 

Friedel-Crafts reaction of isopropylbenzene and 2-methylpropenal diacetate (methacrolein diacetate) in the presence of titanium tetrachloride/boron trifluoride etherate gives cyclamenaldehyde enolacetate, which is hydrolyzed to the aldehyde [151] ... 

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). 

The stereoselective synthesis of (+)-trichodiene was accomplished by K.E. Harding and co-workers. The synthesis of this natural product posed a challenge, since it contains two adjacent quaternary stereocenters. For this reason, they chose a stereospecific electrocyclic reaction, the Nazarov cyclization, as the key ring-forming step to control the stereochemistry. The cyclization precursor was prepared by the Friedel-Crafts acylation of 1,4-dimethyl-1-cyclohexene with the appropriate acid chloride using SnCU as the catalyst. The Nazarov cyclization was not efficient under protic acid catalysis (e.g., TFA), but in the presence of excess boron trifluoride etherate high yield of the cyclized products was obtained. It is important to note that the mildness of the reaction conditions accounts for the fact that both of the products had an intact stereocenter at C2. Under harsher conditions, the formation of the C2-C3 enone was also observed. 

Similar structures can be realised in low yield from the Friedel-Crafts reaction of 1,4-dimethoxybenzene with substituted phthalic anhydrides (R = Me, Et, i-Pr), which were obtained by the appropriate Diels-Alder synthesis. The acylations were effected in the presence of boron trifluoride etherate as catalyst, followed by demethylation of the product (ref.55). 

Boron trifluoride is a highly moisture-sensitive gas (31). It is utilized in esterification, ether formation, Friedel-Crafts alkylation and acylation, and Lewis acid-catalyzed Diels-Alder reactions. A more widely used, easy-to-handle and convenient liquid source of BF3 is boron trifluoride etherate [BF3-0(C2H5)2] (32). Its main usage as catalyst is in the direct esterification of all types of acids, rearrangements, aldol condensation, and Lewis acid-catalyzed Diels-Alder reactions. It is the most frequently used acid in epoxide ring opening and rearrangement (33). 

Friedel-Crafts reaction catalysts like anhydrous aluminum chloride are readily soluble in the nitroalkanes. Solutions containing up to 50% aluminum chloride are easily prepared in nitroalkane solvents. These catalytically active complexes, AICI3-RNO2, can be isolated and used in solvents other than the nitroalkane. The reactants in the Friedel-Crafts reaction are often soluble in the nitroalkane reaction medium. Other catalysts like boron trifluoride (BF3), titanium tetrachloride (TiC ), and stannic tetrachloride (SnClj) are also soluble in the nitroalkane solvents. Reaction types which use nitroparaffins as solvents include alkylation of aromatics, acetylation of aromatics, halogenations, nitrations, and the reaction of olefins and hydrogen sulfide to yield mercaptans. Nitroparaffins are used with catalysts such as alkyl-metal (e.g., triethylaluminum, vanadium, or titanium) salts in the polymerization reactions of alkylene oxides, epichlorohydrin, propylene, butylene, vinyl chloride, and vinyl ethers. The nitroparaffin acts as an activator for the catalyst or can serve as the reaction solvent. 

A photochemical Friedel-Crafts-type reaction has been used to construct a six-membered ring in the tricycle (113). Irradiation through pyrex of a benzene solution of the phenylacetylcyclohexene (112) in the presence of boron trifluoride etherate gave the c/s-octahydrophenanthrone (113) in 87% yield. ... 

Reactions of Enol Ethers and Esters.—When enol acetylation of a steroid 4-en-3-one with acetic anhydride is catalysed by perchloric acid (or boron trifluoride ), C-acetylation of the enol acetate (373) occurs on prolonged reaction. This step, probably involving acetyl perchlorate ior airs, is akin to Friedel-Crafts acylation of aromatic compounds. Both 6-acetylation and 2-acetyIation are known, although each is prevented by the presence of a methyl group at the site. The products can be of various enolic types (e.g. 374 and 375). 

Boron trifluoride forms a range of complexes with ethers, nitriles and amines. It is commercially available as the adduct Et20 BF3 (12.11). Being a liquid at 298 K, it is a convenient means of handling BF3 which has many applications as a catalyst in organic reactions, e.g. in Friedel-Crafts alkylations and acylations. 

---