Benzene activation

One of the two possible disconnections a is better as it gives us an acyl rather than an alkyl halide and an activated benzene ring. 

This reaction sequence is much less prone to difficulties with isomerizations since the pyridine-like carbons of dipyrromethenes do not add protons. Yields are often low, however, since the intermediates do not survive the high temperatures. The more reactive, faster but less reliable system is certainly provided by the dipyrromethanes, in which the reactivity of the pyrrole units is comparable to activated benzene derivatives such as phenol or aniline. The situation is comparable with that found in peptide synthesis where the slow azide method gives cleaner products than the fast DCC-promoted condensations (see p. 234). 

Several ad hoc studies and discussions in recent years have been centered around the mechanism of aromatic substitution in nitro-activated benzene derivatives. The subject has been reviewed authoritatively. ... 

A careful use of solvent effects should be of great assistance in synthetic chemistry. For example, it may be predicted from the solvent effects described above that in the reaction of 2,4-dichloroquinohne with piperidine the a y ratio should increase in the less polar solvents, although the result might be obscured by the mutual influence of the two chlorine substituents. Nitro-activated benzenes support this prediction since ortho para ratios of 4.2 in methanol and 69 in benzene were observed in the reaction of 2,4-dichloronitrobenzene with piperidine. ... 

In non-polar solvents, the reaction with piperidine is best represented by a two-term kinetic form indicating a mixed 2nd- and 3rd-order reaction. Also, base catalysis by tri-ri-butylamine was observed. This kinetic pattern is strongly reminiscent of the results obtained with nitro-activated benzenes.Another interesting result is that stepwise replacement of chlorine atoms by amino groups results in marked... 

The chemistry of pyrrole is similar to that of activated benzene rings. In general, however, the heterocycles are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and Friedel-Crafts acylation can all be accomplished. For example ... 

The y-nitrogen atom of a sulfonic acid azide is electrophilic and reacts in an electrophilic aromatic substitution with an activated benzene or naphthalene derivative, e.g., a phenoxide ion, forming a l-tosyl-3-aryltriazene (2.47). The 1,4-quinone diazide is obtained by hydrolysis (Scheme 2-30, Tedder and Webster, 1960). The general applicability of this reaction seems to be doubtful. With 1-naphthol the 1,2-naphthoquinone diazide was obtained, not the 1,4-isomer. 

Hydridotris(pyrazolyl)borate (N,N,N)-containing ruthenium(ll) complexes activate benzene in stoichiometric amounts to give the isolable complex B. A catalytic hydroarylation of ethylene led to ethylbenzene and a ca. 1 1 mixture of branched and linear alkylbenzenes was obtained when employing propylene (Equation (62)).63,63a... 

For intermolecular hydrocarbon activation, we are not aware of any example where compelling evidence exists for C-H activation directly by square-planar four-coordinate Pt(II), without preceding (or concomitant) ligand loss. In one example, such a direct reaction may take place but the alternative explanation involving ligand loss is also consistent with the data. The compound (dmpe)PtMe(02CCF3) (dmpe = bis(dimethylphosphino)ethane) activates benzene C-H bonds at elevated temperature (125 °C) (23). This reactivity contrasts with that of (dmpe)PtMeCl which is inactive at the same temperature or even at... 

A related base-promoted C-H activation of benzene by Pt(II) was recently reported. With the tridentate monoanionic amido pineer ligand N3 , the triflate complex N3 Pt(OTf), depicted in Scheme 8 was shown to activate benzene in the presence of base (35). It was noted that the chloro complex N3 PtCl was not reactive under these conditions. The activity of the triflate complex again appears to result from the higher lability of triflate which can allow for coordination of the hydrocarbon. 

Optically active benzene(poly)carboxamides and benzene(poly)carboxy-lates were used by Inoue and co-workers as sensitizers for the geometrical photoisomerization of (Z)-cyclooctene and (Z,Z)-cyclooctadienes in various solvents at different temperatures. Under energy-transfer conditions, enantiomeric excesses up to 64% ee in unpolar solvents like pentane were reported. The use of polar solvents diminished the product ee s due to the intervention of a free or solvent-separated radical ion pair generated through the electron transfer from the substrate to the excited chiral sensitizer (Scheme 58) [105-109]. 

Chemisorphon of the complexes [Cp MR2], [Cp MR3] or [MR4] (Cp = Cp, Cp M = Zr, Ti, Th R = Me, CH2 Bu, CH2TMS) onto superacidic sulfated zirconia (ZRS , where x refers to activation temperature) [81, 91] and sulfated y-alumina (AIS) [90] afforded active benzene hydrogenation catalysts and ethylene polymer-izahon catalysts. The most active catalyst system for the hydrogenation of benzene (arene Zr = 1.5 1, 25 °C, no solvent, 0.1 MPa H2) was [Cp ZrMe2] -ZRS400, which achieved a TOP of 970 h. The activity of this adsorbate catalyst rivals or exceeds those of the most active heterogeneous arene hydrogenahon catalysts known. The... 

Such a representation is referred to as a local ionization potential map. Local ionization potential maps provide an alternative to electrostatic potential maps for revealing sites which may be particularly susceptible to electrophilic attack. For example, local ionization potential maps show both the positional selectivity in electrophilic aromatic substitution (NH2 directs ortho para, and NO2 directs meta), and the fact that TC-donor groups (NH2) activate benzene while electron-withdrawing groups (NO2) deactivate benzene. 

Protonated HCN (8) is resonance-stabilized, shows only limited imidocarbocation character and reacts only with activated benzene derivatives but not with benzene. 

Whereas various reactions of phenotellurazines and particularly of phe-noxatellurine have been thoroughly studied, information on the reactivity of tellurantrene is rather scarce and reactions of phenothiatellurine are practically unstudied. The chemical behavior of heterocyclic compounds 92 is determined by the presence in these tricyclic systems of two reaction centers represented by a tellurium and a second heteroatom M (NR, O, S) and also by a tendency of the activated benzene rings to enter into electrophilic substitution reactions. We shall follow this classification of reactions of tricyclic systems 92. 

Fig. 6.2. Variation in transition-state structure with electrophile reactivity in reactions of substituted benzenes. A, Activated benzene (e.g., anisole) B. deactivated benzene (e.g., nitrobenzene).

Alkenes are protonated by HF to give carbocations. Fluoride ion is a weak nucleophile and does not immediately attack the carbocation. If benzene (or an activated benzene derivative) is present, electrophilic substitution occurs. The protonation step follows Markovnikov s rule, forming the more stable carbocation, which alkylates the aromatic ring. 

In the presence of aluminum chloride, an acyl chloride reacts with benzene (or an activated benzene derivative) to give a phenyl ketone an acylbenzene. The Friedel-Crafts acylation is analogous to the Friedel-Crafts alkylation, except that the reagent is an acyl chloride instead of an alkyl halide and the product is an acylbenzene (a phenone ) instead of an alkylbenzene. 

The mechanism of Friedel-Crafts acylation (shown next) resembles that for alkylation, except that the electrophile is a resonance-stabilized acylium ion. The acylium ion reacts with benzene or an activated benzene derivative via an electrophilic aromatic substitution to form an acylbenzene. 

The Gatterman-Koch synthesis is a variant of the Friedel-Crafts acylation in which carbon monoxide and HC1 generate an intermediate that reacts like formyl chloride. Like Friedel-Crafts reactions, the Gatterman-Koch formylation succeeds only with benzene and activated benzene derivatives. 

Friedel-Crafts Acylation of Aromatic Rings In the presence of aluminum chloride, acyl halides acylate benzene, halobenzenes, and activated benzene derivatives. Friedel-Crafts acylation is discussed in detail in Section 17-11. 

Useful electrophilic substitutions occur only on pyridines having electron-donating substituents such as NH2 or OMe. These activate benzene rings too (Chapter 22) but here their help is vital. They supply a nonbonding pair of electrons that becomes the HOMO and carries out the reaction. Simple amino- or methoxypyridines react reasonably well ortho and para to the activating group. These reactions happen in spite of the molecule being a pyridine, not because of it. 

Cp 2Ln(CH3) also activates benzene, and readily undergoes hydrogenolysis ... 

This experiment illustrates the Friedel-Grafts alkylation of an activated benzene molecule with a tertiary alcohol in the presence of sulfuric acid as the Lewis acid catalyst. As in the reaction of benzene and /-butyl chloride, the substitution involves attack by the electrophilic trimethylcarbocation. 

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