Friedel Crafts with titanium tetrachloride

A study of alkylations with a group of substituted benzyl halides and a range of Friedel-Crafts catalysts has provided insight into the trends in selectivity and orientation that accompany changes in both the alkyl group and the catalysts. There is a marked increase in substrate selectivity on going from / -nitrobenzyl chloride to /i-methoxybenzyl chloride. For example, with titanium tetrachloride as the catalyst, Aitoi Abenz increases from 2.5 to 97. This increase in substrate selectivity is accompanied by an increasing preference for para substitution. With /i-nitrobenzyl chloride, the ortho para ratio is 2 1 (the... 

Compared to the relatively young history of the pure metal, aluminium compounds have been known for ages from the above-cited alum class to the more exclusive transition metal-doped aluminium oxides like ruby and sapphire (corundum varieties with chromium for the former and titanium and iron impurities for the latter) or aluminosilicate-like emeralds (a beryl type with chromium and vanadium impurities). However, to the synthetic chemist, aluminium chloride, is de facto one of the first jewels of the aluminium family. Aluminium trichloride (together with titanium tetrachloride, tin tetrachloride and boron trifluoride) is an exemplary Lewis acid that finds many applications in organic synthesis It is extensively used for instance in Friedel-Crafts alkylations and acylations, in Diels-Alder-type cycloadditions and polymerisation reactions. Its involvement in a wide range of reactions has been documented in many reviews and book chapters. ... 

Preparation by Friedel-Crafts acylation of 2,6-di-tert-butylphenol with propionyl chloride in the presence of titanium tetrachloride in ethylene dichloride [7717]. Preparation by Fries rearrangement of 2,6-di-tert-butylphenyl propionate with titanium tetrachloride in nitromethane at 20° for a week (66%) [7712]. 

Oki and his co-workers (177) also found that these halogenated compounds (107) exhibited enormous differences in reactivity when they were treated with Lewis acids. The sc form undergoes a Friedel-Crafts type cyclization in the presence of titanium tetrachloride, which is a weak Lewis acid, whereas the ap form survives these conditions. The latter reacts in the presence of the stronger Lewis acid antimony pentachloride. This difference is apparently caused by a chloro group in proximity to the site where a cationic center develops during the reaction (Scheme 12). 

The catalytic activity of certain of the Friedel-Crafts catalysts was shown to decrease over a very wide range in the series boron fluoride, aluminum bromide, titanium tetrachloride, titanium tetrabromide, boron chloride, boron bromide and stannic chloride (Fairbrother and Seymour, mentioned in Plesch al., 83). When boron fluoride is added to isobutylene at dry ice temperatures, the olefin is converted to a solid polymer within a very few seconds. The time required for complete polymerization with aluminum bromide hardly extends to a few minutes while reaction times of hours are required with titanium chloride and periods of days with stannic chloride. 

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). 

Acetylbenzo[6]tellurophene is also formed in isolable quantities. Benzo[6]selenophene is converted into 2-acyl derivatives by reaction with acid chlorides in the presence of aluminum chloride, whereas similar Friedel-Crafts acylation of benzo[6]thiophene yields 3-substituted products. When the 2-position is blocked, formylation can be directed into the 3-position. Thus treatment of 2-bromobenzo[6]selenophene with dichloromethyl butyl ether (Cl2CHOBu) and titanium tetrachloride yields the 3-formyl derivative (72BSF3955). If the 2- and 3-positions of benzo[6]selenophene are blocked with methyl groups, acylation under Friedel-Crafts conditions occurs in the 6-position (78CR(C)(287)333>. 

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

Protection of phenols by the foregoing methods is complicated by the rapid Friedel-Crafts rearrangement of the nascent rm-butyl ether. By using trifluoro-methanesulfonic add at -78 PC, the rate of /erf-butyl ether formation is fast and the Friedel-Crafts alkylation does not compete [Scheme 4.126].226 Similarly, attempts to deprotect phenol ferf-butyl ethers with trifluoroacetic acid or titanium tetrachloride may give complex mixtures, again as a result of Friedel-Crafts alkylation of the phenol but this side reaction can be suppressed by using a catalytic amount of trifluoromethanesulfonic acid in 2.2,2-trifluoroethanol as solvent at -5 DC. 

Because olefins are soft bases and most Friedel-Crafts halides are hard acids, the primary interaction between these two types of compounds must be regarded as a weak one, the outcome of which is nerally limited to the equilibrium formation of the relatively feeble rr-complex. Only with the softer of the strong Lewis acids would one expect this interaction to proceed further and give direct Hunter-Yohe initiation titanium tetrachloride seems to comply with such a requirement, as suggested by the experimental evidence discussed in Sect. IV-B4-b). 

BTF is known to react with strong Lewis-Acids such as AICI3. [42] However, milder Lewis-Acids do not readily react with BTF. Zinc chloride catalyzed Friedel-Crafts acylation (8.1) leads to better yields in refluxing BTF compared to sym-tetrachloroethane. [43] The deactivating trifluoromethyl group is presumably responsible for the inertness of BTF towards aromatic substitution under these conditions. Titanium tetrachloride has successfully been used for Sakurai [44]... 

Aluminum chloride is the most fiequently used Lewis acid in aliphatic Friedel-Crafts acylations, and is one of the strongest. Its complexes with acyl halides are strong, producing very active acylating species. Titanium and tin tetrachlorides also find use as catalysts, and are powerful enough to induce reaction at low temperatures. 

Silicon has also been used to control the acylation of 1,3-dienes in a manner analogous to the situation with alkenes. Isoprenylation with 2-trimethylsilylmethylbuta-1,3-diene follows the course expected of acylation of the allylic silane. In these very rapid reactions, titanium tetrachloride seems to be one of the more efficient catalysts, as is aluminum chloride. The method was used in synthetic approaches to the terpenes ipsenol (14) and ipsdienol (15 Scheme 16). Of particular interest is the comparison of this iso-prenylating agent with isoprene itself. The examples of Friedel-Crafts acylations cited show the regio-control that can be achieved by suitable choice of substrate. 

Produced annually in ton quantities (2). They are industrial objectives for which the riedel-Crafts strategy has frequently been used. From the point of view of pollution prevention, there are a number of reasons why alternatives must be considered. The Friedel-Cr ts pathway involves corrosive and air sensitive acid chlorides, Lewis acids such as duminum chloride, stannic chloride or titanium tetrachloride and solvents such as nitrobenzene, carbon disulfide, carbon tetrachloride or methylene chloride (3). Althou some research directed toward minimizing the amount of Lewis acid needed for the Friedel-Crafts reaction has been reported, this modification requires elevated temperatures (4). Friedel-Crafts reactions conducted with acidic resins nave also been reported. This research appears promising but is in the early stages (5). Obviously, an attractive alternative to the traditional Friedel-Crafts reaction would have an impact on pollution prevention. 

Only recently, the diastereoselective synthesis and preparative separation of the enantiomers of galaxolide (Givaudan) have been described. [169] The titanium tetrachloride-catalysed Friedel-Crafts alkylation of 1,1,2,3,3-pentamethylin-dane with (S)-propylene oxide produces two epimeric alcohols (whereby no racemisation is observed) with paraformaldehyde and catalytic amounts of sulfuric acid, these are converted into the desired isochroman diastereomers. The separation of the epimers is accomplished by means of the corresponding chro-... 

Titanium tetrachloride is a moisture-sensitive, highly flammable liquid reacting violently with water (34). It is a strong Lewis acid capable of promoting Diels-Alder reactions (35) and induces the addition of silyl enol ethers and allyl silanes to carbonyl compounds and derivatives (34r-36). It is a less commonly used catalyst in Friedel-Crafts reactions but very useful for the acylation of activated alkenes and in the Fries rearrangement. 

Nitroparaffins afford an unique reaction medium for Friedel-Crafts reactions since these solvents will dissolve Lewis acid catalysts such as anhydrous aluminum chloride (AICI3), boron trifluoride (BF3), titanium tetrachloride (TiCl4), and stannic tetrachloride (SnC ). The role of nitromethane as a metal stabilizer for various chlorinated and fluorinated solvents involves its ability to complex with metal salts like aluminum chloride from the solvent-metal reaction. 

Blin et al. determined the transfer and termination constants for the cationic polymerization of 1-and 2-vinylnaphthalenes and 3-vinylphenanthrene in methylene chloride and titanium tetrachloride as initiator [340]. For each monomer these constants increased with increasing temperature. Their values were significantly larger than those of styrene at the same conditions. This is supposed to be a consequence of the existence of highly reactive aromatic sites, which permit Friedel-Crafts attacks by the growing chain. 

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. 

Preparation by Friedel-Crafts acylation of o-tert-butylphenol with benzoyl chloride in ethylene dichloride in the presence of titanium tetrachloride, first with ice cooling, then for 5 h at r.t. (44%) [816]. 

---