Positional selectivity nitration

Low Substrate and High Positional Selectivity. Nitrations with nitronium tetrafluoroborate in nitromethane and nitronium hexa-fluorophosphate in nitromethane solution, respectively, show low substrate selectivities (generally expressed by the k /kg rate ratios) but at the same time the nitrations maintained high positional selectivity. Typical isomer distributions in the nitration of toluene are 6 J% ortho, k% meta, and 29% para nitrotoluene. The data summarized in Table XIV show the relative reactivities of a number of alkylbenzenes over those of benzene, together with the isomer distributions of the mononitro products. 

These data clearly show that low substrate and low positional selectivity nitration reactions, can indeed, take place. The high reactivity of the reagent is responsible for low selectivity concerning both substrates and positions. These reactions are, however, very different frcm the observed nitronium salt nitrations in which positional selectivity stays high. 

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

Because nitration has been studied for a wide variety of aromatic compounds, it is a useful reaction with which to illustrate the directing effect of substituent groups. Table 10.3 presents some of the data. A variety of reaction conditions are represented, so direct comparison is not always valid, but the trends are nevertheless clear. It is important to remember that other electrophiles, while following the same qualitative trends, show large quantitative differences in position selectivity. 

The identification of a specific nitrating species can be approached by comparing selectivity with that of nitration under conditions known to involve the nitronium ion. Examination of part B of Table 10.7 shows that the position selectivity exhibited by acetyl nitrate toward toluene and ethylbenzene is not dramatically different from that observed with nitronium ion. The data for i-propylbenzene suggest a lower ortho para ratio for acetyl nitrate nitrations. This could indicate a larger steric factor for nitration by acetyl nitrate. 

Tnflic acid is an excellent catalyst for the nitration of aromatic compounds [.S7]. In a mixture with nitnc acid, it forms the highly electrophilic nitronium inflate, which can be isolated as a white crystalline solid Nitronium inflate is a powerful nitrating reagent in inert organie solvents and in tnflic acid or sulfuric acid. It nitrates benzene, toluene, chlorobenzene, nitrobenzene, m-xylene, and benzotn-fluoride quantitatively in the temperature range of-110 to 30 °C with exeeptionally high positional selectivity [87],... 

Schneider and Busch have showed that tetraazafS 1 8 l paracyclophane catalyzes the nitration of alkyl bromides with sodiiun nitrite In dioxane-water d l at 30 C, the reaction of 2-bromomethylnaphthalene with sodiiun nitrite is accelerated by a factor of 20 in the presence of the catalyst Concomitantly, the product ratio of [R-ONO [RNO-, changes from 0 50 1 to 016 1 Thus, an acciuruiladon of nitrite ions at the positively charged cyclophanes or IRA-900-nitrite form provides a new method for selective nitration of alkyl halides... 

Given this behavior (little selectivity in distinguishing between different substrate molecules), the selectivity relationship would predict that positional selectivity should also be very small. However, it is not. For example, under conditions where nitration of p-xylene and 1,2,4-trimethylbenzene takes place at about equal rates, there was no corresponding lack of selectivity at positions within the latter. Though... 

The nitration of naphthalene was used as a test reaction [37]. As a consequence of having two aromatic rings, a particularly large variety of nitration products are in principle possible. This refers to multiplicity of nitration and to positional selectivity for each nitration step. 

Nitration of a series of mesomeric betaines was extensively studied in connection with their potential use as explosives (Scheme 3). Nitration of l,2,3-triazolo[2,l- ]benzotriazole 74 can be achieved selectively, occurring first at the 7-position which is followed by nitration at the 3- and 5-positions. Thus, nitration with 45% nitric acid gives a mixture of 7-nitro derivative 75 (39%) and dinitro derivative 76 (58%), while 70% nitric acid yields a mixture of 3,7- (52%), 5,7- (23%), and 3,5-dinitro (5%) isomers 76-78. Clean trinitration to 3,5,7-trinitro-l,2,3-triazolo[2,l- ]benzotriazole 79... 

There are many testimonies for the cation-radical formation during electrophilic aromatic nitration. Positional selectivities are in line with spin-density distributions. In principle, the attack of N02 radical is probably at the position of the aromatic cation-radical, which bears the maximal spin density. 

The exact position of nitrate bands (at 1274 and 1276 cm 1 for EPDM and polyoctenamer respectively) is consistent with the selective formation of secondary hydroperoxides (a)15. 

Nitronium tetrafluoroborate used in large excess (>6 equiv.) is able to transform hexamethylbenzene and its derivatives to dinitroprehnitene (1,2,3,4-tetramethyl-5,6-dinitrobenzene) in a highly selective nitration process486 [Eq. (5.180)]. Scheme 5.47 summarizes the key steps of the mechanistic proposal, including the ipso - n i tro are n iu m ion 123, the formation of benzyl nitrite 124, and the complexation of the N02+ ion to form the mononitro intermediate (125) facilitating the attack to the ortho position resulting in the formation of the 1,2-dinitro product. 

Table 4-1 compares two different reactions, namely, anode oxidation and oxidation with cerium ammonium nitrate (which are bona fide electron-transfer processes) and bromination by /V-bromosuccinimide in the presence of azobis(iso-butyro)nitrile (which is bona fide hydrogen-atom-transfer process). Both electron-transfer and hydrogen-atom-transfer processes have the benzylic radical as a common intermediate, but positional selectivity is stronger for electron-transfer processes. Another important point is the preference of the 2-positioned methyl group over the 1-positioned group, in terms of selectivity. For 1,2,3-tetramethylbenzene, such a preference reaches values from 16 to 55, and it is over 200 for 5-methoxy-1,2,3-tctramcthylbcnzcnc. 

The possibility mentioned in (4) is of great importance, and centres on the persistence in nitrations with nitronium salts of positional selectivities in the nitration of alkylbenzenes. It is discussed in 6.2. 

The positional selectivity for proton exchange is partly mirrored in nitrations, quinoline gives approximately equal amounts of 5- and 8-nitro-quinolines, whereas isoquinoline produces almost exclusively the... 

The general mechanistic framework outlined in this section can be elaborated by other details to more fully describe the mechanisms of the individual electrophilic substitutions. The question of the identity of the active electrophile in each reaction is important. We have discussed the case of nitration in which, under many circumstances, the electrophile is the nitronium ion. Similar questions about the structure of the active electrophile arise in most of the other substitution processes. Another issue that is important is the ability of the electrophile to select among the alternative positions on a substituted aromatic ring position selectivity). The relative reactivity and selectivity of substituted benzenes toward various electrophiles is important in developing a firm understanding of EAS. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

---