Friedel-Crafts initiators

Friedel—Crafts Initiators in the Cationic Polymerization of pam-Substituted a -Methylstyrenes... 

My teaching experience was, however, only secondary to my research interest. Through my initial research work involving reactions of fluorinated carbohydrates I became interested in Friedel-Crafts acylation and subsequently alkylation reactions with acyl or alkyl fluo-... 

Haloall lation. Haloalkyl groups can be introduced directiy by processes similar to Friedel-Crafts alkylation into aromatic and, to some extent, ahphatic compounds. Because halo alkylations involve bi- or polyfunctional alkylating agents, they must be performed under conditions that promote the initial halo alkylation but not, to any substantial degree, subsequent further alkylations with the initially formed haloalkylated products. 

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Friedel-Crafts (Lewis) acids have been shown to be much more effective in the initiation of cationic polymerization when in the presence of a cocatalyst such as water, alkyl haUdes, and protic acids. Virtually all feedstocks used in the synthesis of hydrocarbon resins contain at least traces of water, which serves as a cocatalyst. The accepted mechanism for the activation of boron trifluoride in the presence of water is shown in equation 1 (10). Other Lewis acids are activated by similar mechanisms. In a more general sense, water may be replaced by any appropriate electron-donating species (eg, ether, alcohol, alkyl haUde) to generate a cationic intermediate and a Lewis acid complex counterion. 

In place of a proton source, ie, a Briimsted acid, a cation source such as an alkyl haUde, ester, or ether can be used in conjunction with a Friedel-Crafts acid. Initiation with the ether-based initiating systems in most cases involves the haUde derivative which arises upon fast haUdation by the Friedel-Crafts acid, MX (2). 

When using a cation source in conjunction with a Friedel-Crafts acid the concentration of growing centers is most often difficult to measure and remains unknown. By the use of stable carbocation salts (for instance trityl and tropyhum hexachloroantimonate) the uncertainty of the concentration of initiating cations is eliminated. Due to the highly reproducible rates, stable carbocation salts have been used in kinetic studies. Their use, however, is limited to cationicaHy fairly reactive monomers (eg, A/-vinylcarbazole, -methoxystyrene, alkyl vinyl ethers) since they are too stable and therefore ineffective initiators of less reactive monomers, such as isobutylene, styrene, and dienes. 

The mechanism of initiation in cationic polymerization using Friedel-Crafts acids appeared to be clarified by the discovery that most Friedel-Crafts acids, particularly haUdes of boron, titanium, and tin, require an additional cation source to initiate polymerization. Evidence has been accumulating, however, that in many systems Friedel-Crafts acids alone are able to initiate cationic polymerization. The polymerization of isobutylene for instance can be initiated, reportedly even in the absence of an added initiator, by AlBr or AlCl (19), TiCl ( )- Three fundamentally different... 

Further dechlorination may occur with the formation of substituted diphenyhnethanes. If enough aluminum metal is present, the Friedel-Crafts reactions involved may generate considerable heat and smoke and substantial amounts of hydrogen chloride, which reacts with more aluminum metal, rapidly forming AlCl. The addition of an epoxide inhibits the initiation of this reaction by consuming HCl. Alkali, alkaline-earth, magnesium, and zinc metals also present a potential reactivity hazard with chlorinated solvents such as methylene chloride. 

It is not possible to polymerise vinyl ethers by free-radical-initiated methods but, as with isobutylene polymers, it is possible to make polymers using Friedel-Crafts type catalysts. 

There are relatively few kinetic data on the Friedel-Crafts reaction. Alkylation of benzene or toluene with methyl bromide or ethyl bromide with gallium bromide as catalyst is first-order in each reactant and in catalyst. With aluminum bromide as catalyst, the rate of reaction changes with time, apparently because of heterogeneity of the reaction mixture. The initial rate data fit the kinetic expression ... 

Initiation. A Friedel-Craft acid (hydrochloric acid, water, phenol) is used as initiator together with a proton source ( co-initiator , BF3 or AICI3 are the most common). The mixture produces a catiogen which is the true initiating species. 

In an initial step the reactive formylating agent is formed from N,N-dimethylformamide (DMF) 2 and phosphorus oxychloride. Other N,N-disubstituted formamides have also found application for example A -methyl-A -phenylformamide is often used. The formylating agent is likely to be a chloromethyl iminium salt 4—also called the Vilsmeier complex (however its actual structure is not rigorously known)—that acts as the electrophile in an electrophilic substitution reaction with the aromatic substrate 1 (see also Friedel-Crafts acylation reaction) ... 

The initial series of major tranquilizers consists of alkylated derivatives of 4-aryl-4-hydroxypiperidines. Construction of this ring system is accomplished by a set of rather unusual reactions. Condensation of methylstyrenes with formaldehyde and ammonium chloride afford the corresponding hexahydro-1,3-oxazines (119). Heating these oxazines in the presence of acid leads to rearrangement with loss of water to the tetrahydropyridines. Scheme 1 shows a possible reaction pathway for these transformations. Addition of hydrogen bromide affords the expected 4-bromo compound (121). This last is easily displaced by water to lead to the desired alcohol (122) The side chain (123) is obtained by Friedel-Crafts acylation of p-fluorobenzene with 4-chloro-butyryl chloride. Alkylation of the appropriate arylpiperidinol with 123 affords the desired butyrophenone derivative. Thus,... 

Strategy A Friedel-Crafts reaction involves initial formation of a carbocation, which can rearrange by either a hydride shift or an alkyl shift to give a more stable carbocation. Draw the initial carbocation, assess its stability, and see if the shift of a hydride ion or an alkyl group from a neighboring carbon will result in increased stability. In the present instance, the initial carbocation is a secondary one that can rearrange to a more stable tertiary one by a hydride shift. 

Further, while conventional Friedel-Crafts halides produce high molecular weight polyisobutylenes or polyisobutylene copolymers (e.g., butyl rubbers, HR) only at relatively low ( —100 °C) temperatures, alkylaluminum-based initiator systems produce high molecular weight materials at much higher ( —40 °C) temperatures. 

Since initiation with conventional Friedel-Crafts halides cannot be controlled, the fine-tuning of reactions becomes extremely cumbersome. In contrast, by the use of alkylaluminum compounds elementary events (initiation, termination, transfer) become controllable and thus molecular engineering becomes possible. Indeed, by elucidating the mechanism of initiation etc., a large variety of new materials, i.e., block3, graft4-6 bigraft7 copolymers, have been synthesized and some of their physical-chemical properties determined. 

Alkenes can be acylated with an acyl halide and a Lewis acid catalyst in what is essentially a Friedel-Crafts reaction at an aliphatic carbon. ° The product can arise by two paths. The initial attack is by the acyl cation RCO (or by the acyl halide free or complexed see 11-14) at the double bond to give a carbocation ... 

Rearrangement can also occur after the initial alkylation. The reaction of 2-chloro-2-methylbutane with benzene is an example of this behavior.35 With relatively mild Friedel-Crafts catalysts such as BF3 or FeCl3, the main product is 1. With A1C13, equilibration of 1 and 2 occurs and the equilibrium favors 2. The rearrangement is the result of product equilibration via reversibly formed carbocations. 

The first compounds of this class46 have been obtained via Route A. The initial condensation of phthalic anhydride with dimethylaniline requires a Friedel-Crafts catalyst, while condensation of the resulting benzophenone with the indole requires acetic anhydride. For Route B preparation of the intermediate l,2-dimethyl-3-(2-carboxybenzoyl)indole has also been described47 by condensation of the two components in the presence of aluminum chloride. However, in our experience, aluminum chloride is, in this case, unnecessary, thus rendering this route the method of choice. 

In 1978, Sugasawa et al., at Shionogi Pharmaceutical Co. reported ortho-selective Friedel-Craft acylation with free anilines with nitrile derivatives [4]. Sugasawa reported that the reaction requires two different Lewis acids (BC13 and A1C13) and does not proceed when N,N-dialkyl anilines are used. He proposed that boron bridging between nitriles and anilines led to exclusive ortho-acylation but a conclusive mechanism was not elucidated. The report did not offer any reason why two different Lewis acids were required and why the reaction did not progress with N,N-dialkyl anilines. Therefore, we initiated mechanistic studies. 

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