Reactivity, alkyl halides with variation

In other variations ketones are produced. The acyliron monoanion may be alkylated again with another alkyl halide to form a transient acyl-alkyl iron intermediate, which rapidly decomposes into ketone and the polynuclear iron carbonyl complex. This reaction is limited, however, because only very reactive alkylating agents such as methyl, allyl, and benzyl halides will react with the weakly nucleophilic acyliron monoanions ... 

The results obtained in the gas-phase isopropylation of various aromatic hydrocarbons with isopropyl chloride over Nafion-H catalyst showed only a relatively small variation of reactivity in going from fluorobenzene to xylenes.235 Therefore, it has been assumed that the reaction rate is controlled by the formation of a reactive electrophilic intermediate (possibly, protonated alkyl halide 61, or some form of incipient alkyl cation) rather than by cr-complex formation between the electrophile and the aromatic nucleus [Eq. (5.89)]. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion. Phase-transfer catalysis, ultrasound,and the use of reactive clays are important variations. Substrates other than alkyl halides have been... 

Some actual data may help at this point. The rates of reaction of the following alkyl chlorides with Kl in acetone at 50 °C broadly Illustrate the patterns of S 2 reactivity we have just analysed. These are relative rates with respect to n-BuCI as a typical primary halide. You should not take too much notice of precise figures but rather observe the trends and notice that the variations are quite large—the full range from 0.02 to 100,000 is eight powers of ten. 

Table 1.1 shows that, for a given electrophile (CH3I) and standard conditions, the rate constants for common nucleophiles vary by a factor of well over a billion (10 ). This tremendous variation of reactivity of the different nucleophiles might pose a conundrum in relation to their synthetic utility. Note (from either Table 1.1 or 1.2) that alkoxide (RO ) anions are some 10 -10" times more nucleophilic than neutral alcohols, and the rates for carboxylate anions (RC02 ), relative to the un-ionized carboxylic acids, differ by even more 10 -10 . With such low rates, are alcohols and carboxylic acids, in their un-ionized forms, at all useful as nucleophiles The answer is a clear yes. In acidic media, many of the anionic nucleophiles simply don t exist they are entirely protonated. Under such conditions, weak nucleophiles such as alcohols and carboxylic acids react effectively with cationic electrophiles such as carbocations. Second, although weaker nucleophiles may not react at a useful rate with alkyl halides, many of them do react at perfectly acceptable rates... 

Variations in the R—X reactant include alkyl, aryl, alkenyl, benzyl, allyl, and propargyl halides. The reactivity of the halogen atom, of course, influences these reactions greatly, phenyl or vinyl halides are sluggish compared to the more reactive alkyl, benzyl, allyl, and propargyl halides. For example, reaction of ir-C5H5(CO)2Fe with methyl iodide gives a 70% yield of the methyliron complex, hut reaction with iodobenzene only yields 2% of the phenyliron complex 22). 

A. Mechanism. Alkyl halides undoubtedly represent the most well-tested functional group for nucleophilic reactivity. That superoxide ion reacts with alkyl haldies by an S 2 mechanism has been demonstrated. Dietz, et al., (J) y observed a relative reactivity which fell in the series n-BuBr > sec-BuBr > -BuBr > jt-BuBr for variation of alkyl group structure and in the series n -BuBr > n-BuOTs > n-BuCl for variation of leaving group. The former order is consistent with a Sj 2 reaction mechanism and the latter order suggests that superoxide anion radical is a strong nucleophile. 

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