Ipso position

Neat liquids, unless otherwise specified values for ipso position (carrying substituent) italicized data ... 

We have discussed orientation in the case of monosubstituted benzenes entirely in terms of attack at the ortho, meta, and para positions, but attack at the position bearing the substituent (called the ipsoposition ) can also be important. Ipso attack has mostly been studied for nitration. When NOj attacks at the ipso position there are at least five possible fates for the resulting arenium ion (13). 

Path c. The electrophilic group (in this case NOj) can undergo a 1,2 migration, followed by loss of the proton. The product in this case is the same as that obtained by direct attack of NOj at the ortho position of PhZ. It is not always easy to tell how much of the ortho product in any individual case arises from this pathway, though there is evidence that it can be a considerable proportion. Because of this possibility, many of the reported conclusions about the relative reactivity of the ortho, meta, and para positions are cast into doubt, since some of the product may have arisen not from direct attack at the ortho position, but from attack at the ipso position followed by rearrange-... 

Another hydroxylation reaction is the Elbs reaction In this method, phenols can be oxidized to p-diphenols with K2S20g in alkaline solution. Primary, secondary, or tertiary aromatic amines give predominant or exclusive ortho substitution unless both ortho positions are blocked, in which case para substitution is found. The reaction with amines is called the Boyland-Sims oxidation. Yields are low with either phenols or amines, generally under 50%. The mechanisms are not clear, but for the Boyland-Sims oxidation there is evidence that the S20 ion attacks at the ipso position, and then a migration follows. ... 

An example of this displacement between a pyridine nitrogen atom and an aryl halide is shown in Scheme 21. When 2-pyridyl acetates 138 were C-acylated with 2-halobenzoyl chlorides, the enolized products 139 resulting from the reaction suffered an intramolecular nucleophilic attack of the pyridine nitrogen atom onto the ipso-position to give benzo[c]quinolizinium salts 140 as intermediates. Loss of HC1 gas from 140 afforded benzo[c]quinolizine derivatives 141 <2002JOC2082>. 

Recently, Curran described a procedure using triethylborane for the synthesis of spirooxindoles and spirodihydroquinolones through intramolecular addition of aryl radicals at the ipso position 4-alkoxy-substituted aromatic rings [15]. The key step for a formal synthesis of the vasopressin inhibitor SR121463A is described in Scheme 5. The initiation was performed with Et3B in an open to air reaction vessel. 

Table 4.4 helps us to understand why 1,4- and 1,2-xylenes undergo substitution in the ipso positions (the positions where the methyl groups are located). The electrophilic reagents obviously have to attack the substrate at the position with maximal electron density. These are ipso positions for the cation-radicals of 1,4- and 1,2-isomers. (For the neutral isomers, these are positions where the methyl groups are absent ) The substitution is directed into the ipso positions of 1,4-xylene and ring by up to 76 and 24% only, respectively. In case of 1,2-xylene, the snbstitntion takes place for 60 and 40% at ipso-positions and into the ring, respectively. In 1,3-xylene cation-radical, spin density is maximal in the nonmethylated positions 4 and 6, which are involved in the substitution for 84% (Fisher and Wright 1974). 

Tanaka et al. (2000) reported that N02 nitration of 1,8-dimethylnaphthalene leads to 2-nitro and 4-nitro products. For 2-nitro prodnct, the reaction proceeds as electrophilic substitution—the nitro group comes into the ipso position and then migrates to the position 2, thus giving the final product. For 4-nitro product, the process develops according to electron-transfer ronte. The spin density of 1,8-dimethylnaphthalene cation-radical is highest at position 4 (or, the same, at position 5). It is the para nitration that takes place in the experiment. 

O atom of THF and a rather weak contact with the ipso position of one of the phenyl... 

The presence of a 4-methoxy substituent on the 2-phenylethyloxyl or 3-phenylpropyl-oxyl side chains radically altered the course of these cyclizations (Scheme 4). 31a and 31b afforded the spiro-fused ring systems 32 and 33 in 26 and 69% yields, respectively, as the only cyclization products. With this substituent, cyclization onto the activated ipso positions was favoured over direct attack, even where the strained transition state for Atj -5 cyclization of 31a to 32 was involved. Demethylation of the intermediate spirocyclohexa-dienyl cation is favoured over rearrangement in these cases. Kikugawa and coworkers effected the formation of 32 (82%) and 33 (39%) with reverse efficiencies using AgaCOs in TFA . 

The X-substituted benzene (aniline, Figure 11.2) is activated toward electrophilic attack since the HOMO is raised significantly. The electrophile would be directed to the ortho, para, and ipso positions of the ring and to the X substituent itself. The ipso channel is usually nonproductive since the common heteroatom-based X substituents are not easily displaced as Lewis acids. Loss of substituent is frequently observed with tertiary alkyl-substituted benzenes. Attachment of the electrophile to the X substituent is most likely if... 

The second situation in which ipso attack is favoured is when the addition at the ipso position affords a cr-complex intermediate of considerably greater stability than those arising from the addition at the unsubstituted positions. This can happen with electroneutral radicals also. An example is the reaction of the dinitrothiophene (236) with methyl radicals. Here the intermediate (237) is the most stable radical which can be formed from (236) this therefore leads to the ipso substituted product (238) in 35% yield. 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

Diethyl sodiomalonate is an example of type (i). Reaction with [(fluorobenzene)Cr(CO)3] proceeds to completion after 20 h at 50 C in HMPA to give the diethyl phenylmalonate complex in over 95% yield. Monitoring the reaction by NMR gave no evidence for an intermediate (e.g. the cyclohexadienyl anion complex) interruption of the reaction by addition of iodine at less than 20 h gave significant amounts of unreacted fluorobenzene. A satisfactory picture is the simple one, that the anion adds reversibly and unfavorably (k < k-i, as in Scheme 3), slowly finding itself at the ipso position then irreversible loss of fluoride gives the substitution product.5152... 

There is an alternate mechanism for halide replacement, following the sequence of nucleophile addition, protonation and elimination of HX (Scheme 9). In this pathway, the addition of the nucleophile need not be at the ipso position it can be ortho to halide leading to cine substitution or it can be at the meta or para positions, leading to tele substitution.69,70 The mechanism is the same for both cine and tele substitution and the different names reflect a differentiation in the IUPAC naming schemes. 

III,B,1 we will deal with reactions in which both cine and ipso products are formed. The mechanism according to which these products are formed has been explained by the occurrence of a didehydronaphthyridine (naphthyri-dyne) intermediate.44 In Section III,B,2 the occurrence of aminodehalogena-tions involving tele substitutions are discussed and in Section 1II,B,3 the reactions in which the aminodehalogenation occurs in an ipso position are examined. 

In an analogous way, electron transfer to an acceptor-substituted aromatic like 25 produces a radical anion ot type 26. This is proto-naled in the ipso position to give intermediate 27. A second electron transfer and prolonation leads similarly to product 28. In most cases BuOH proves to be a good source of protons. 

Product formation was interpreted in terms of transalkylation of substituted triphenylmethanes. Protonation at the ipso position of the substituted phenyl ring to form arenium ion 64 followed by the C—C bond breaking yields the diphenylmethyl cation, which alkylates benzene or is stabilized by hydride transfer (Scheme 5.30). The protonated intermediate 64 is highly unstable when the ring has an electron-withdrawing substituent. Consequently, its transformation is extremely slow and the primary product triphenylmethane can be isolated. 

Schuchmann MN, Steenken S, Wroblewski J, von Sonntag C (1984) Site of OH radical attack on dihydrouracil and some of its methyl derivatives. Int J Radiat Biol 46 225-232 Schuler RH, Albarran G, Zajicek J, George MV, Fessenden RW, Carmichael I (2002) On the addition of OH radicals to the ipso position of alkyl-substituted aromatics production of 4-hydroxy-4-methyl-2,5-cyclohexadien-1-one in the radiolytic oxidation of p-cresol. J Phys Chem A 106 12178-12183... 

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