Friedel-Crafts alkylation orientation

In this section, the reactivities of organosilicon compounds for the Friedel-Crafts alkylation of aromatic compounds in the presence of aluminum chloride catalyst and the mechanism of the alkylation reactions will be discus.sed, along with the orientation and isomer distribution in the products and associated problems such as the decomposition of chloroalkylsilanes to chlorosilanes.. Side reactions such as transalkylation and reorientation of alkylated products will also be mentioned, and the insertion reaction of allylsilylation and other related reactions will be explained. 

Answer The nitro groups must be put in by nitration but the orientation is wrong. The methyl group cannot be disconnected as a Friedel-Crafts alkylation would never work on the available but extremely unreactive m-dinitro benzene. The solution (guideline 5) is to introduce a dummy amino group in such a position that it can activali... 

The product is a substituted phenol, whose -OH group directs the orientation of the -C(CH3)3 groups. The precursor to MON-0585 is synthesized by a Friedel-Crafts alkylation of phenol by the appropriate hydrocarbon halide. This compound is synthesized by NBS bromination of the product of alkylation of benzene with 2-chloropropane. 

Most of the support for this mechanism comes from evidence about the nature of the attacking particle in each of these reactions evidence, that is, that substitution is electrophilic. This evidence, in turn, comes largely from kinetics, augmented by various other observations the nitrating power of preformed nitronium salts (Sec. 11.8), for example, or carbonium ion-like rearrangements in some Friedel-Crafts alkylations (Problem 11.3 above). The electrophilic nature of these reactions is supported in a very broad way by the fact that other reactions which show the same reactivity and orientation features also fit into the same mechanistic pattern. 

The experiments in Sections 15.2 and 15.3 illustrate the Friedel-Crafts alkylation and acylation of aromatic hydrocarbons, respectively. A complication of Friedel-Crafts reactions is apparent in the alkylation experiment, wherein rearrangements of the carbo-cations generated from the alkyl halide provide mixtures of substitution products. The acylation reaction of Section 15.3 provides an example of how a combination of electronic and steric effects can affect the orientation of electrophilic attack on an aromatic ring. 

Orientation in Alkylation. An additional factor complicating the usefulness of Friedel-Crafts alkylations is the orientation involved in the introduction of more than one alkyl group. It was discovered at an early date that alkylation with aluminum chloride and alkyl halides yields considerable proportions of m-dialkylbenzenes, as well as the expected o- and jj-isomers. The relative extent of normal and abnormal orientation has been found to be a function of the conditions of alkylation. In general, the more vigorous the conditions with respect to the activity of the catalyst or the alkylating agent or the severity of the time and temperature factors, the greater is the tendency for the forma-... 

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... 

Many di- and poly-alkylated benzenes have been prepared by the Friedel-Crafts reaction. Alkyl groups on the nucleus do not exert a strong directive influence upon the orientation, nor do they greatly affect the rate of further alkylation. The composition of the alkylated product varies widely, depending upon the conditions of the reaction. Appreciable quantities of m-dialkylated and sywz-trialkylated products are obtained under vigorous conditions. The composition of many products is in doubt, as has been shown by later, more accurate analyses. Methylation of xylene gives 1,2,4,5-tetramethylbenzene (durene), pentamethylbenzene, and hexamethylbenzene. ... 

One rather interesting aspect of the Friedel-Crafts reaction is that trialkylation of benzene often leads to a symmetrical 1,3,5-isomer rather than a 1,2,4-derivative as would be expected from the ortho-para orientation of the alkyl group introduced initially. Since alkylation by the Friedel-Crafts method has been shown to be a reversible reaction,68 this anomalous orientation has been explained on the basis that both alkylation and dealkylation occur readily in the ortho and para positions. Simultaneously, however, some alkylation occurs in the meta position but no dealkylation68 If the reaction mixture is allowed to stand in contact with aluminum chloride for some length of time, then principally meta trialkyl derivatives will be formed ... 

Since alkylation by the Friedel-Crafts reaction has been demonstrated to be a reversible reaction,it has been suggested that the various anomalous orientations can be expUuned on this baris. Jacobs sen was the first of many to point out that normal alkyla-... 

Identification. The many possibilities for the formation of isomeric or anomalous products due to rearrangement, unusual orientation, or degradation of alkyl groups during the Friedel-Crafts reaction, coupled with the fact that the products are usually liquids, difficult to separate and identify, frequently necessitate particular care in establishing the structure and the purity of the products. The most effective method... 

Is bromination a special case The answer is no nitration, sulfonation, and Friedel-Crafts reactions of the alkylbenzene give similar results— mainly ortho and para substitutions (see also Table 16-2 in Section 16-3). Evidently, the nature of the attacking electrophile has hole influence on the observed orientation it is the alkyl group that matters. Because there is virtually no meta product, we say that the activating methyl substituent is ortho and para directing. 

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