Aromatic substitution product

Only one example, showing high stereoselectivity, is known in this class of reactions. On treatment of the acyclic glycine cation equivalent 1 (see Appendix), containing the ( + )-cam-phor-10-sulfonamide ester as a chiral auxiliary, with boron trifluoridc and anisole at 0"C a mixture of aromatic substitution products is obtained in essentially quantitative yield 55. Besides 11 % of cuV/io-substitution product, the mixture contains (R,S)-2 and its (/ ,/ )-epimer in a ratio >96 4 (NMR). The same stereoisomer 2 predominates when the reaction is conducted in sulfuric acid/acetic acid 1 9, although the selectivity is slightly lower (91 9 besides 25% of ortho substitution). 

Sulfonyl nitrenes react with benzene to produce appreciable yields of aromatic substitution products. The nitrene thermally generated in benzene from 229 gives a monosubstitution product. When the reaction is carried out in mesitylene as a solvent, the two sulfonylnitrenes react with mesitylene to afford 230 (equation 140)135. 

The thermal, but not the photochemical, decomposition of ferro-cenylsulphonyl azide (14) in benzene gave some intermolecular aromatic substitution product FCSO2NHC6H5 (6.5%) but no intermolecular cyclization product (17). Contrariwise, photolysis of 14 in benzene gave 17 but no anilide 1 ). 

Small amounts of aromatic substitution product are often formed during halogen-metal exchange. Many mechanisms are possible. 

Various substituted cyclopropanes have been shown to undergo nucleophilic addition of alcoholic solvents. For example, the electron transfer reaction of phenylcyclopropane (43, R = H) with p-dicyanobenzene resulted in a ring-opened ether 44. This reaction also produced an aromatic substitution product (45, R = H) formed by coupling with the sensitizer anion. This reaction is the cyclopropane analog of the photo-NOCAS reaction, but preceded it by almost a decade. 

In several photochemical electron transfer reactions, addition products are observed between the donor and acceptor molecules. However, the formation of these products does not necessarily involve direct coupling of the radical ion pair. Instead, many of these reactions proceed via proton transfer from the radical cation to the radical anion, followed by coupling of the donor derived radical with an acceptor derived intermediate. For example, 1,4-dicyanobenzene and various other cyanoaromatic acceptors react with 2,3-dimethylbutene to give aromatic substitution products, most likely formed via an addition-elimination sequence [140]. 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

Base-catalyzed The parent phenol complex 85 undergoes a variety of base-catalyzed Michael addition reactions at room temperature to generate 4H-phenol complexes in yields in the range 79-99 % (Table 14) [29]. Michael additions with MVK, methyl acrylate, acrylonitrile, N-methylmaleimide, cydopentenone, and crotonaldehyde (entries 1-6, respectively) proceed with high regio- and stereocontrol. Demetalation and isolation of the dienone is typically accompanied by tautomerization to the aromatic substitution product. 

Electrophihc aromatic substitutions are unhke nucleophilic substitutions in that the large majority proceed by just one mechanism with respect to the substrate. In this mechanism, which we call the arenium ion mechanism, the electrophile (which can be viewed as a Lewis acid) is attacked by the 71-electrons of the aromatic ring (behaving as a Lewis base in most cases) in the first step. This reaction leads to formation of a new C—X bond and a new sp carbon in a positively charged intermediate called an arenium ion, where X is the electrophile. The positively charged intermediate (the arenium ion) is resonance stabilized, but not aromatic. Loss of a proton from the sp carbon that is adjacent to the positive carbon in the arenium ion, in what is effectively an El process (see p. 1487), is driven by rearomatization of the ring from the arenium ion to give the aromatic substitution product. A proton... 

Decomposition of aUcyl azides with aluminium chloride in benzene at 50° gave products which corresponded to the formation of a carbonium ion (loss of N3 ) and to an electron-deficient nitrogen (loss of N2) . For example, cyclohexyl azide gave phenylcyclohexane (30%), cyclohexanone imine (90) (15%) and the ring-expanded imine (91) (30-40%). The same workers reported the first example of an aUcyl nitrenium ion being trapped by benzene in reasonable yieldIn the presence of three equivalents of aluminium chloride in benzene, azidoacetone (92) gave the aromatic substitution product (93) in 35%... 

Decomposition of methanesulphonyl azide in aromatic solvents (methyl benzoate or benzotrifluoride), in the presence of transition metal compounds (e.g. copper(ri) acetylacetonate, manganese(ii) acetylacetonate, di-cobalt octacarbonyl, tri-iron dodecacarbonyl, and iron pentacarbonyl) led to a marked decrease in the aromatic substitution product compared with thermolysis, and, with the iron carbonyls, to an increased yield of methanesulphonamide . In addition, the aromatic substitution products shifted from mainly ortAo-substitution with no additives to mainly w ia-substitution in the presence of the additives mentioned above. 

When CH3Li or n-BuLi is used in halogen-metal exchange, a rather electrophilic MeX or n-BuX is obtained as a by-product. The alkyl halide can undergo S 2 substitution with the organolithium compound as nucleophile to give the nucleophilic aromatic substitution product. However, Sn2 reactions of organolithium compounds with alkyl... 

Problem 3.11. Draw mechanisms explaining the formation of both electrophilic aromatic substitution products. 

Draw the electrophilic aromatic substitution product below. The E adds just once. 

The ionic addition of bromine to cis- and ra i -diphenylcyclopropane (1 R = Ph, H R = H, Ph) gave 1,3-addition products only, while phenylcyclopropane (1, R = R = H) also gave some aromatic substitution products. The rate of reaction and the ratio of stereoisomers in the product composition were highly sensitive to light, heat, and change in solvent. 

The reaction of a nucleophilic alkyl radical R with benzene affords the a-complex 1, a fairly stable cyclohexadienyl radical, which under oxidizing conditions leads to cation 2 (Scheme 1). Depending on the stability of the attacking radical, the formation of 1 is a reversible process. Deprotonation eventually affords the homolytic aromatic substitution product 3. If the reaction is performed under non-oxidizing conditions, cyclohexadienyl radical 1 can dimerize (—> 4), disproportionate to form cyclohexadiene 5 and the arene 3, or further react by other pathways [3]. 

Additions of benzoyloxy radicals to double bonds" and aromatic rings (Scheme 3.79) are potentially reversible. For double bond addition, the rate constant for the reverse fragmentation step is slow (A 10"-10 s at 25 °C) with respect to the rate of propagation during polymerizations. Thus, double bond addition is effectively irreversible. However, for aromatic substrates, the rate of the reverse process is extremely fast. While the aromatic substitution products may be trapped with efficient scavenging agents (e.g. a nitroxide " or a transition... 

When an unactivated aryl halide (333) is treated with a very strong base, an elimination reaction is possible that generates an intermediate called a benzyne (336). Benzyne is electron deficient and will be attacked by nucleophiles in a reaction that opens the Jt bond not part of the aromatic cloud, and produces a new carbanion (337). Protonation completes the sequence to give the aromatic substitution product 338. 

The relative ratio of tail, head, and aromatic addition was determined by decomposing benzoyl peroxide (BPO) in styrene containing the radical trapping agent 1 (Scheme 12) [148]. The tail addition product 9a accounted for of the benzoyloxy derived products while the head addition 11a only accounted for 5%. Aromatic substitution products 13a accounted for the other 15% of the benzoyloxy radicals. The ratio of these products was however somewhat dependant upon the concentration of 1. This is likely due to the relative rates of addition to styrene and of 1 to benzyl radical 8a and primary alkyl radical 10a. 

Work by Kotschy and co-workers showed that reactions of different symmetrical 1,2,4,5-tetrazines with a variety of organometallic reagents furnished, depending upon the combination of reactants, azaphilic addition, reduction or complexation products and not the nucleophilic aromatic substitution products <2004T1991>. On the other hand, Benson et al. reported a smooth displacement of one chlorine substituent in chlorotetrazine 136 using cyanide anion as a soft C-nucleophile (Scheme 36) <2000T1165>. 

Bromination of substituted oxazoles can yield normal aromatic substitution products or 4,5- and 2,5-addition products, depending on the reaction conditions. For example, Hassner and Fischer " brominated 2,5-diphenyloxazole 111 with bromine in acetic acid and sodium acetate to prepare 4-bromo-2,5-diphenyloxazole 595 (Scheme 1.163). Similarly, Belen kii and co-workers isolated a mixture of 5-bromo-2-phenyloxazole 596 and 4,5-dibromo-2-phenyloxazole 597 from treatment of 2-phenyloxazole 5 with bromine in refluxing benzene. Lawson and VanSant " isolated 2-amino-5-bromo-4-(trifluoromethyl)oxazole 599a and 5-bromo-2-(methylamino)-4-(trifluoromethyl)oxazole 599b from bromination of 2-amino-4-(trifluoromethyl)oxazole 598a and 2-(methylamino)-4-(trifluoromethyl) oxazole 598b, respectively, with bromine in acetic acid and sodium acetate. 

Highly reactive methylene iminium chlorides 250 were used by Kaupp for carbon-carbon formation in arylaminomethylations of 2-naphthol in a ball mill (Scheme 2.79) [67], Due to susceptibility of iminium chlorides to moisture, reagents were handled under an argon atmosphere. After milling, electrophilic aromatic substitution products 252 were dissolved in dihloromethane and recrystallized. The... 

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