Deactivators strong

Kinetic data are available for the nitration of a series of p-alkylphenyl trimethylammonium ions over a range of acidities in sulphuric acid. - The following table shows how p-methyl and p-tert-h xty augment the reactivity of the position ortho to them. Comparison with table 9.1 shows how very much more powerfully both the methyl and the tert-butyl group assist substitution into these strongly deactivated cations than they do at the o-positions in toluene and ferf-butylbenzene. Analysis of these results, and comparison with those for chlorination and bromination, shows that even in these highly deactivated cations, as in the nitration of alkylbenzenes ( 9.1.1), the alkyl groups still release electrons in the inductive order. In view of the comparisons just... 

The first quantitative studies of the nitration of quinoline, isoquinoline, and cinnoline were made by Dewar and Maitlis, who measured isomer proportions and also, by competition, the relative rates of nitration of quinoline and isoquinoline (1 24-5). Subsequently, extensive kinetic studies were reported for all three of these heterocycles and their methyl quaternary derivatives (table 10.3). The usual criteria established that over the range 77-99 % sulphuric acid at 25 °C quinoline reacts as its cation (i), and the same is true for isoquinoline in 71-84% sulphuric acid at 25 °C and 67-73 % sulphuric acid at 80 °C ( 8.2 tables 8.1, 8.3). Cinnoline reacts as the 2-cinnolinium cation (nia) in 76-83% sulphuric acid at 80 °C (see table 8.1). All of these cations are strongly deactivated. Approximate partial rate factors of /j = 9-ox io and /g = i-o X io have been estimated for isoquinolinium. The unproto-nated nitrogen atom of the 2-cinnolinium (ina) and 2-methylcinno-linium (iiiA) cations causes them to react 287 and 200 more slowly than the related 2-isoquinolinium (iia) and 2-methylisoquinolinium (iii)... 

A more detailed study of the nitration of quinolinium (l) in 80-05 % sulphuric acid at 25 °C, using isotopic dilution analysis, has shown that 3-) 5-) 6-, 7- and 8-nitroquinoline are formed (table 10.3). Combining these results with the kinetic ones, and assuming that no 2- and 4-nitration occurs, gives the partial rate factors listed in table 10.4. Isoquinolinium is 14 times more reactive than quinolinium. The strong deactivation of the 3-position is in accord with an estimated partial rate factor of io for hydrogen isotope exchange at the 3-position in the pyridinium ion. It has been estimated that the reactivity of this ion is at least 10 less than that of the quinolinium ion. Based on this estimate, the partial rate factor for 3-nitration of the pyridinium ion would be less than 5 x io . 

As with cases mentioned earlier, Hiickel m.o. theory performs satisfactorily in predicting the orientation of nitration in these oxides, but again fails to reproduce their strong deactivation. ... 

Our analysis of substituent effects has so far centered on two groups methyl and triflu oromethyl We have seen that a methyl substituent is activating and ortho para directing A trifluoromethyl group is strongly deactivating and meta directing What about other substituents ... 

Table 12 2 summarizes orientation and rate effects m electrophilic aromatic sub stitution reactions for a variety of frequently encountered substituents It is arranged m order of decreasing activating power the most strongly activating substituents are at the top the most strongly deactivating substituents are at the bottom The mam features of the table can be summarized as follows... 

Very strongly deactivating 0 II —CCI —C=N —SO3H -CF3 —NO2 (acyl chloride) (cyano) (sulfonic acid) (trifluoromethyl) (nitro) Meta directing... 

The next group of substituents in Table 12 2 that we 11 discuss are the ones near the bottom of the table those that are meta directing and strongly deactivating... 

As Table 12 2 indicates a variety of substituent types are meta directing and strongly deactivating We have already discussed one of these the trifluoromethyl group Several of the others have a carbonyl group attached directly to the aromatic ring... 

Substituent Effects in Electrophilic Aromatic Substitution Strongly Deactivating Substituents... 

Aluminum chloride is a stronger Lewis acid than iron(lll) bromide and has been used as a catalyst in electrophilic bromination when as in the example shown the aromatic ring bears a strongly deactivating substituent... 

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... 

The cyano, nitro, and quaternary ammonium groups are strongly deactivating and weto-directing. Electrophilic substitutions of compounds with these substituents require especially vigorous conditions and fail completely with all but the most reactive electrophiles. 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

Lewis acid catalysts such as aluminum chloride and iron(III) halides also bond to nitrogen to strongly deactivate the ring toward Friedel-Crafts reactions and halogenation. 

Typically, an acetanilide (1 mol. equiv.) was treated with the Vilsmeier reagent generated from POCI3 (7 mol. equiv.) and V,V-dimethylformamide (DMF, 2.5 mol. equiv.) at 75 °C for 4 - 20 h. The reaction products were readily obtained by filtration after pouring the reaction mixture onto ice-water minor reaction products were isolated after basification of the filtrate. A variety of acetanilides were studied under these optimised reaction conditions and some significant observations were noted. Activated acetanilides 3 [e.g. R = 4-Me (70%), 4-OMe (56%)] reacted faster and in better yield to give quinolines 4 than other strongly deactivated systems 3 [e.g. R = 4-Br (23%), 4-Cl (2%), 4-NO2 (0%)] — in these cases, formamidines 5 and acrylamides 6 were the major reaction products. 

The Vilsmeier cyclisation of acetanilides by the conventional methods described above often requires long reaction times and elevated temperatures. Moreover, only activated acetanilides react efficiently to afford 2-chloro-3-substituted-quinolines strongly deactivated systems afford mainly amidine 5 or acrylamide 6. ... 

From resonance structure (12) it is obvious that a —I—M-substit-uent strongly deactivates the 2-position toward electrophilic substitution, and one would thus expect that monosubstitution occurs exclusively in the 5-position. This has also been found to be the case in the chlorination, bromination, and nitration of 3-thiophenecarboxylic acid. Upon chlorination and bromination a second halogen could be introduced in the 2-position, although further nitration of 5-nitro-3-thiopheneearboxylic acid could not be achieved. Similarly, 3-thiophene aldehyde has been nitrated to 5-nitro-3-thiophene aldehyde, and it is further claimed that 5-bromo-3-thiopheneboronic acid is obtained upon bromination of 3-thiopheneboronic acid. ... 

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