Boron Trifluoride1

BF3

[7637-07-2]  · BF3  · Boron Trifluoride  · (MW 67.81)

(strongly oxophilic Lewis acid)

Physical Data: gas, mp -127 °C; bp -100 °C/35 mmHg.1,2

Solubility: very sol water, and forms a mono- and dihydrate; it is only partially hydrolyzed to fluoroboric acid. Also sol most organic solvents such as pentane; forms complexes with compounds that contain heteroatoms with lone pair electrons.

Form Supplied in: gas in cylinders or lecture bottles; widely available.

Preparative Method: made by heating calcium fluoride with boron trioxide or from potassium fluoroborate with concentrated sulfuric acid. The product may be contaminated by silicon tetrafluoride unless the starting materials are free from silicon.1b,2

Purification: via distillation and aromatic addition compound formation.40

Handling, Storage, and Precautions: a monel metal valve or stainless steel regulator is recommended. Extremely moisture sensitive; should be used with carefully dried apparatus. Irritant, slowly hydrolyzes to give HF. All work must be carried out in an efficient fume hood.

Introduction.

Boron trifluoride acts as a Lewis acid but its major reactivity relates to the fact that the boron reagent is oxophilic, whereas Aluminum Chloride is mostly known for its reactions with halides.3 Thus many of the reactions of boron trifluoride involve alcohols, ethers, carboxylic acids, and esters; the water which is frequently eliminated coordinates with the boron trifluoride. Esters are formed in the presence of boron trifluoride by the interaction of acids with alcohols,4 acids with ethers,5 and amides with alcohols and phenols.6 Thus phenyl acetate is rapidly formed when phenol and acetamide are treated with boron trifluoride. Propene, in the presence of boron trifluoride, reacts with carboxylic acids to form isopropyl esters,7 and with phenol to form the isopropyl ether.8 When salicylic acid is treated with boron trifluoride and then propene the ester, isopropyl salicylate, is formed rapidly. With an excess of propene, isopropyl 2-hydroxy-3,5-diisopropylbenzoate is formed in an almost quantitative yield.7 Ketones that are enolizable are converted into b-diketones in the presence of carboxylic anhydrides and boron trifluoride.9 Similarly, phenyl alkyl ethers afford alkyl phenols.10,11 Benzidine and Beckmann rearrangements and the rearrangement of phenyl acetate to 4-hydroxyacetophenone have all been studied using boron trifluoride.3 A number of the early investigations have been repeated.

Friedel-Crafts Alkylation Reactions.

Alcohols react with benzene12 or naphthalene13 to give alkylated products. The alkylation of benzene using cyclohexanol (eq 1) gives moderate yields, but no other alcohols give better results; for example, both 1-propanol and 2-propanol give mono- and 1,4-diisopropylbenzene in a combined yield of ca. 38%.12a The reactions of isobutanol with benzene in the presence of boron trifluoride, not unexpectedly, give t-butyl- and 1,4-di-t-butylbenzene.12e Similarly, naphthalene is alkylated in good yield using cyclohexanol (eq 2).13

The alkylation of aromatic hydrocarbons using alkyl fluorides has also been investigated. Although the reactivity of boron trifluoride is lower than that of the other boron halides, the yields are usually better when using the fluoride. Methyl, ethyl, propyl, isopropyl, t-butyl, and cyclohexyl fluorides were shown to alkylate aromatic compounds in good yields. For example, benzene and cyclohexyl fluoride give the expected product in 85% yield.12b Normally, alkylation does not occur using alkyl halides other than the fluorides, and mixed halides afford products containing halogen. Although the reaction of cyclohexyl fluoride was successful, an attempted reaction using cyclohexyl bromide with toluene was unsuccessful.12b The preparation of cumene in high yield can be achieved using 2-fluoropropane in a reaction with benzene (eq 3); the lack of reactivity of other halogens is exemplified by the reaction of 1-chloro-3-fluoropropane, in which the product is 1-chloro-2-phenylpropane, and by eq 4, where the bromine is retained using 1-bromo-2-fluoroethane.14

The use of alkenes as sources of the electrophiles involved in Friedel-Crafts alkylations has also been studied. In early examples the yields obtained were not as good as in alkylations using alcohols. For example, the yield of 2-cyclohexylnaphthalene is only 35% using cyclohexene.13 On the other hand, the intramolecular alkylation of 1-(2-tolyl)-(E)-pent-3-ene gives 1,5-dimethyl-1,2,3,4-tetrahydronaphthalene in 95% yield, and the example shown in eq 5 was used in a synthesis of 1,3,6,8-tetramethyltriphenylene.15 Related to this latter reaction, gaseous boron trifluoride has been shown to form a complex with nitromethane, which is particularly effective in catalyzing proton-initiated cascade cyclizations like the one shown in eq 6.16

Diastereoselective alkylation reactions of furans have been studied using diacetoxypyrrolidinones as sources of an acyliminium ion. Good yields and some diastereoselection were observed when using Zinc Bromide or Chlorotrimethylsilane as the Lewis acid but, unfortunately, no diastereoselection was observed using boron trifluoride.17

Friedel-Crafts Acylation Reactions.

The acylation of particularly electron-rich aromatic compounds can be achieved by a number of procedures; the number of options available that allow formylations to be carried out are fewer. The Vilsmeier protocols apply only to nucleophilic aromatic substrates, for example indoles and pyrroles. Formylation reactions using carbon monoxide, hydrogen chloride, and aluminum chloride function as if Formyl Chloride were produced. It is known, however, that formyl chloride is unstable at temperatures above -60 °C. On the other hand, Formyl Fluoride, which may be prepared by the interaction of anhydrous hydrogen fluoride with the mixed anhydride of formic and acetic acids, and removed as it is formed (bp -29 °C), has been used in conjunction with boron trifluoride. Alkylbenzenes are formylated at low temperatures. In an alternative procedure, formyl fluoride and boron trifluoride are passed into a solution of the aromatic hydrocarbon in carbon disulfide.18 Thus benzene gives benzaldehyde (56%), mesitylene gives mesitaldehyde (70%), and naphthalene gives a 1:5 mixture of a- and b-naphthaldehydes.

In other acylation reactions, acyl fluorides and boron trifluoride afford ketones with better regioselectivity than that observed with aluminum chloride as the Lewis acid. A reaction of isobutyryl fluoride with 2-methylnaphthalene gives an excellent yield of the product shown in eq 7.19

Boron trifluoride can, however, give rise to difficulties as a result of side-chain acylation, as exemplified in eq 8.20 Carboxylic acids have been used in reactions of phenols21 and aryl ethers together with boron trifluoride. Dealkylation of an ether residue ortho to the introduced acyl group is frequently encountered, as in the synthesis of baeckeol (eq 9).22 Advantage of this effect was also taken in a synthesis of the naturally occurring phenol aurentiacin, as shown in eq 10.23

Carbonyl Group and Related Transformations.

The conversion of aldehydes and ketones into the related gem-difluoro compounds is effected by treatment with Molybdenum(VI) Fluoride at rt in the presence of catalytic amounts of boron trifluoride. The yields with ketones are significantly better than with aldehydes.24 The acylation of enolizable carbonyl compounds was mentioned in the introduction.9 A checked procedure for the acetylation of acetone, which affords pentane-2,4-dione in 80-85% yield, has been reported.25 In general, it has been established that better yields of b-diketones are obtained if the intermediate boron difluoride complexes are isolated.26 The boron difluoride complexes, isolated in yields of 75-92%, give the b-diketones in yields of 76-95%; the procedure is exemplified in eq 11. In another study, evidence was presented that implicated two mechanisms for the acetylation of ketones.27 One route involves the formation of the enol acetate and the other involves the direct acetylation of the boron enolate. Thus the enol acetate derived from cyclohexanone is formed and isolated in 22% yield in a reaction in which cyclohexanone is allowed to interact with acetic anhydride in the presence of 14 mol % of boron trifluoride gas. The enol acetate was subsequently shown to afford 2-acetylcyclohexanone in 76% yield when treated with acetic anhydride and boron trifluoride. On the other hand, attempts to form the enol acetate from acetophenone were unsuccessful.

The alkylation of b-keto esters using an alcohol as the source of the electrophile can be effected by using boron trifluoride (eq 12).28

Beckmann rearrangements using boron trifluoride3 have been investigated in more detail. For example, benzophenone oxime affords a 1:1 complex in 98% yield when boron trifluoride is passed into a solution of the oxime in light petroleum. The complex rearranges to N-phenylbenzamide in 83% yield when heated to 140-150 °C. The related benzophenone oxime O-methyl ether-boron trifluoride complex also gives N-phenylbenzamide at a lower temperature but in lower yield.29 The isomerization of syn- to anti-arylaldoximes has also been reported via the boron trifluoride complexes.30

Cation-Assisted Rearrangement Reactions.

A number of interesting cyclization reactions leading to naturally occurring polycyclic ring systems have been investigated using boron trifluoride. The cedrane ring system is formed (eq 13) when the enol acetate is treated as shown; reaction of the ketone with Methyllithium then gives racemic cedrol.31 In a detailed study of the reactions of an acetoxymenthadiene (eq 14), it was shown that racemic camphor can be obtained in 90% yield when a 0.1 % solution in wet dichloromethane is treated with boron trifluoride at room temperature for 10 min. Lower yields are obtained when higher concentrations of the diene are used, and boron trifluoride etherate fails to afford any of the required product as do other Lewis acids.32 A Lewis acid-assisted fragmentation followed by a 1,2-methyl shift, driven by the enolate, is involved in the terpene rearrangement leading to the nootkatane skeleton shown in eq 15.33 Rearrangement reactions of glycidic esters have been studied using boron trifluoride and are found to proceed in high yields.34 For example, ethyl b-phenylglycidate gives ethyl phenylpyruvate, isolated in 80% yield as the 2,4-dinitrophenylhydrazone.

Diels-Alder Reactions.

Lewis acid-catalyzed Diels-Alder reactions are well known, and a number of examples have been studied using boron trifluoride. The regioselectivity of the reaction of unsymmetrical dienes with unsymmetrically substituted quinones can be directed in favor of either regioisomer depending on the catalyst used. This is exemplified in eq 16.35 The regioselectivity has been explained on the basis that boron is capable of forming a tetracoordinate complex, whereas tin can complex via the more basic oxygen and the adjacent methoxy group. The analogous reaction using piperylene (penta-1,3-diene) shows, as expected, slightly improved regioselectivity. A study of diastereoselective Diels-Alder reactions using acrylate esters of 3,4-O-methylene-b-D-arabinoside has involved the use of a number of Lewis acids, including boron trifluoride.36

Miscellaneous Reactions.

The nitration of benzene derivatives using methyl nitrate in nitromethane in the presence of a Lewis acid leads to the formation of significant amounts of chlorinated products when using chlorine-containing Lewis acids. Side-chain nitration is also a problem sometimes. On the other hand, the nitrations of tetra- and pentamethylbenzenes proceed efficiently when boron trifluoride is used. Pentamethylbenzene affords the nitro derivative in an almost quantitative yield and durene gives mononitrodurene in 97% yield. When using a 3:1 excess of methyl nitrate and boron trifluoride, durene converts quantitatively into dinitrodurene.37

The reduction of alcohols using a trialkylsilane in the presence of a protic acid can be complicated by skeletal rearrangement and alkene formation as a result of carbenium ion formation. This problem is significantly reduced when using boron trifluoride as the acid (eq 17).38 The preparation of peptide isosteres (eq 18) and related model compounds (eq 19) is achieved by the reductive elimination of g-oxygenated-a,b-unsaturated carboxylates using boron trifluoride complexes of alkenylcopper reagents.38

Finally, it is of interest to note that a-difluoroamino fluoroimines fragment to a-difluoroamino fluorides in dichloromethane in the presence of boron trifluoride (eq 20).39

Related Reagents.

Boron Trifluoride-Acetic Acid; Boron Trifluoride-Dimethyl Sulfide; Boron Trifluoride-Acetic Anhydride; Boron Trifluoride Etherate; Hydrogen Peroxide-Boron Trifluoride; Iodosylbenzene-Boron Trifluoride; Lithium Dimethylcuprate-Boron Trifluoride; Methylcopper-Boron Trifluoride Etherate; Phenylcopper-Boron Trifluoride Etherate; Tetrafluoroboric Acid.


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Harry Heaney

Loughborough University of Technology, UK



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