Protonation - ipso

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

The acid-catalyzed rearrangements of substituted pyrroles and thiophenes consequent on ipso protonation have been referred to previously (Section 3.02.2.4.2). There is some evidence that these rearrangements are intramolecular in nature since in the case of acid-induced rearrangement of 2-acylpyrroles to 3-acylpyrroles no intermolecular acylation of suitable substrates could be demonstrated (Scheme 10) (8UOC839). 

The reaction is second order, first order in phenol and first order in the methylene-bridged aromatic (27), Presumably the mechanism involves ipso protonation of the aromatic followed by attack of phenol on the cationic intermediate (27). When applied to coals, it renders them almost completely extractable into pyridine, and the number average molecular weights of the extractable material generally range between 300 and 750 (24). 

Extensive studies of naphthalenium cations were later reported by Lammertsma and Cerfontain.1314 Figure 2 summarizes the H NMR data and A<513C values for a series of isomeric monomethyl-, dimethyl-, trimethyl-, and tetramethylnaphthalenium, as well as for hexahydropyrenium mono- and dications. Methyl groups exert strong directive and charge-stabilizing effects. The hexahydropyrenium dication shows dramatic charge localization in the ortho positions. Ipso protonation is observed with 1,4,5-trimethyl and 1,2,3,4-tetramethyl derivatives. 

A series of substituted anthracenium monocations were generated by van der Griendt and Cerfontain (only proton data are available).15 A noteworthy feature is the anisotropic shielding of methyl in i/wo-protonated ethyl-substituted carbocations. A similar effect is seen in one of the methyl groups for the ipso-protonated isopropyl derivative. 

Related resins 8e [349] and 8f [350] have been used in Suzuki coupling reactions cleavage was possible under conditions of lower acid concentration for 8f, attributable to anchimerically assisted ipso protonation by the amide carbonyl. Similar observations have been made concerning the conditions required to cleave this silane anchoring group from a linker that had been attached to benzhydrylamine resin [351]. 

The ipso protonation deserves a special scrutiny is discussed earlier. Here we show that the additivity rule is operative for the ipso protonation too, if proper reference level is found. Let us consider multiply substituted fluorobenzenes. They are schematically depicted in Fig.7. It is obvious that the proton affinity of benzene cannot serve as a gauge value for the ipso protonation. Instead, we shall employ once again homodesmic reactions and proceed as follows. Protonation at position 1 of 1,2,3-trifluorobenzene will provide an illuminating example in this respect. The corresponding homodesmic reactions read ... 

Here, the ipso protonation at position 1 of 1-fluorobenzene is denoted by the subscript 1, whereas ortho and meta signify positions of other substituent(s) relative to the proto-nation site. The difference A = (c5 - 6+) determines deviations from strict additivity. It will appear that S and cancel to a large extent, although their particular values are sometimes not negligible. Relation (18) is easily generalized to encompass polyfluorinated benzenes ... 

Ipso proton affinities of fluorinated benzenes (17)-(24) as estimated by the MP2(I) model and by the additivity formula (21) in kcal/mol. ... 

The first index within parentheses denotes ipso protonation, whereas remaining indices determine positions of the remaining F atoms relative to the protonated C atom. 

It is interesting to point out that the lowest proton affinity in polyfluorinated naphthalenes is found for ipso protonation (viz. systems 33, 35 and 36). It is a consequence of the out-of-plane shift of fluorine and the accompanying ring puckering. However, this is at the same time a manifestation of the rr-electron fluoro effect put forward by Liebman et al. [45]. It is very well known that multiply fluorinated compounds possess considerably stabilized a-MOs if the systems are planar, the 7r-manifold being almost unaffected [46]. However, in nonplanar systems all MOs at the carbon skeleton are significantly stabilized [45,46] which is exactly the ceise for the ipso protonation. Now, it can be easily shown... 

First, a ring-closure barrier ( TS3,4) leads to arene oxide products directly. Second, a proton-shuttle mechanism transfers the ipso-proton from the substrate in Icat to one of the nitrogen atoms of the porph5rrin ring to give the proton-transfer intermediate ( PT) via a barrier TSa s. In PT, the aromaticity has come back into the ring, and the structme can be seen as a phenolate... 

Several examples of dearylation reactions have also been reported [79]. These are thought to proceed through ipso protonation of aryl groups [80], with formation of a a-complex (91) and... 

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