Friedel alkylation

In each case the configuration around the boron changes from trigonal planar to tetrahedral on adduct formation. Because of this ability to form additional compounds, boron trifluoride is an important catalyst and is used in many organic reactions, notably polymerisation, esterification, and Friedel-Crafts acylation and alkylations. 

We will show here the classification procedure with a specific dataset [28]. A reaction center, the addition of a C-H bond to a C=C double bond, was chosen that comprised a variety of different reaction types such as Michael additions, Friedel-Crafts alkylation of aromatic compounds by alkenes, or photochemical reactions. We wanted to see whether these different reaction types can be discerned by this... 

The Friedel-Crafts Reaction, in which an aromatic hydrocarbon reacts with an alkyl halide under the influence of aluminium chloride ... 

Friedel and Crafts reaction. alkyl halide condenses with an aromatic hydrocarbon in the presence of anhydrous aluminium chloride to yield, in the first instance, a hydrocarbon in accordance with the following scheme —... 

Other catalysts which may be used in the Friedel - Crafts alkylation reaction include ferric chloride, antimony pentachloride, zirconium tetrachloride, boron trifluoride, zinc chloride and hydrogen fluoride but these are generally not so effective in academic laboratories. The alkylating agents include alkyl halides, alcohols and olefines. 

It should be noted that the Friedel-Crafts acylation differs from the Friedel-Crafts alkylation (compare Sections IV,3-4 and discussion preceding Section IV,1) in one important respect. The alkylation requires catal3d.ic quantities of aluminium chloride, but for acylation a molecular equivalent of aluminium chloride is necessary for each carbonyl group present in the acylating agent. This is because aluminium chloride is capable of forming rather stable complexes with the carbonyl group these complexes probably possess an oxonium... 

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-... 

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. 

The formation of the (X-delocalized norbornyl cation via ionization of 2-norbornyl precusors in low-nucleophilicity, superacidic media, as mentioned, can be considered an analog of an intramolecnlar Friedel-Crafts alkylation in a saturated system. Indeed, deprotonation gives nortricyclane,... 

Again we want to use Friedel-Crafts but we must use acylation rather than alkylation or we shall get rearrangement. 

Review Problem 6 Some chemists who were investigating the possibility of reversible Friedel-Crafts reactions, wanted an activated aromatic ring cormected to a branched alkyl chain and chose to make TM 82. How would you do it ... 

Synthesis This route has been carried out successfully (Rec. Trav. Chem., 1958, 77, 854). Note that no AICI3 is needed for Friedel-Crafts alkylation with easily formed t-alkyl compounds. 

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

Laurino examined a similar method in which methanesulfonanilides were alkylated with bromoacetaldehyde diethyl acetal and then cyclized with TiCU[4J. 1 hese methods presumably involve generation of an electrophilic intermediate from the acetal functionality, followed by an intramolecular Friedel-Crafts reaction. As a consequence, the cyclization is favoured by ER substituents and retarded by EW groups on the benzene ring. 

All attempts to prepare selenazole derivatives by the Gatterman (for-mylation) or Friedel-Crafts (alkylation) methods failed (19, 26). indicating that the electrophilic reactivity of the 5-position is less than that of benzene or toluene. 

Friedel-Crafts alkylation Alkyl halides react with benzene in the presence of alu minum chloride to yield alkylbenzenes... 

Alkylation of benzene with alkyl halides m the presence of aluminum chloride was discovered by Charles Friedel and James M Crafts m 1877 Crafts who later became president of the Massachusetts Institute of Technology collaborated with Friedel at the Sorbonne m Pans and together they developed what we now call the Friedel-Crafts reaction into one of the most useful synthetic methods m organic chemistry... 

Secondary alkyl halides react by a similar mechanism involving attack on benzene by a secondary carbocation Methyl and ethyl halides do not form carbocations when treated with aluminum chloride but do alkylate benzene under Friedel-Crafts conditions The aluminum chloride complexes of methyl and ethyl halides contain highly polarized carbon-halogen bonds and these complexes are the electrophilic species that react with benzene... 

One drawback to Fnedel-Crafts alkylation is that rearrangements can occur espe cially when primary alkyl halides are used For example Friedel-Crafts alkylation of benzene with isobutyl chloride (a primary alkyl halide) yields only tert butylbenzene... 

FIGURE 12 7 The mechanism of Friedel-Crafts alkylation The molecular model depicts the cyclohexadienyl cation intermediate formed in step 1... 

Another version of the Friedel-Crafts reaction uses acyl halides instead of alkyl halides and yields aryl ketones... 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

Vinylic halides and aryl halides do not form carbocations under conditions of the Friedel-Crafts reaction and so cannot be used in place of an alkyl halide or an acyl halide... 

It IS sometimes difficult to limit Friedel-Crafts alkylation to monoalkylation... 

Isopropylbenzene is prepared by the Friedel-Crafts alkylation of benzene y using isopropyl chloride and aluminum chloride (Section 12 6) j... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Friedel-Crafts alkylation (Section 12 6) An electrophilic aro matic substitution in which an aromatic compound reacts with an alkyl halide in the presence of aluminum chloride An alkyl group becomes bonded to the nng... 

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