Functionalization of the benzene ring

The ability to selectively direct chemistry at indole positions C4 to C7 remains a synthetic challenge. Takayama and co-workers have developed a procedure for masking the 2,3-Jt bond of indole as a bridged ethylene glycol system that allowed for functionalization of the 

A synthesis of thiazolo[5,4-e]indoles from 5-aminoindoles was reported 05TL2865 . The key step was an NBS-mediated regioselective annulation of a 5-thiourea-substituted indole. 

An approach to benzocanthinones and related analogues involved a radical cyclization of halo-substituted 1-acylcarbazoles and 1-acylcarbolines 05T9102 . 

An iterative directed-metallating approach to 4,5-substituted indoles starting from gramine was documented 05T6886 . Treatment of gramine 173 with tert-butyllithium and trimethylsilylmethylazide followed by Boc protection gave 4-aminoindole 174. Directed lithiation by the carbamate followed by treatment with DMF gave indole 175. 

In a beautifully choreographed sequence of events, Judd and co-workers installed the C3 to C4 bridged bicyclic lactam moiety of 129 with diastereoselective control via an Ugi 4-component coupling, ring-closing metathesis, and Heck reaction 07OL5119 . 

In a new application of a classic method for aromatic substitution, the Buszek group has prepared 4,5-, 5,6- and 6,7-indolynes from the corresponding dihaloindoles. The aryne intermediates were trapped with furan to access a range of polycylic frameworks 07OL4135 . 

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A diazonium salt reacts with hypophosphorus acid (H3PO2) to form benzene. This reaction has limited utility because it reduces the functionality of the benzene ring by replacing Ng with a hydrogen atom. Nonetheless, this reaction is useful in synthesizing compounds that have substitution patterns that are not available by other means. 

Benzisothiazole moieties substituted at C-3 with an oxygen are also present in compounds studied for /3-adrenoceptor blocking activity such as 266 [90]. These compounds were prepared as racemic mixtures from 265 by a coupling reaction of the epoxide function of the benzene ring with the various amine derivatives (Scheme 67). 

PROBLEM 23.22 What is the function of the benzene ring of polystyrene Could any ring-containing polymer have been used Would cyclohexane have done as well, for example ... 

Dissolving metal reductions of the benzene rings are especially important with functional derivatives of benzene such as phenols, phenol ethers and carboxylic acids (pp. 80, 82,93 and 140). 

In aromatic systems, the Lewis acids which activate via coordination are also capable of activating the aromatic system by the formation of a and ir complexes. There are a sufficient number of examples available to indicate that the activation via the latter processes is the more important of these, where all are present. Olivier (52) showed in 1913 that the kinetic behavior of such reactions consists of two portions. When the catalyst, say aluminum chloride, is present in less than the amount required to complex all the functional groups, the reaction is relatively slow and the catalytic activity is due to the small amount of Lewis acid resulting from the dissociation of the complex. As soon as all the functional groups are coordinated, any additional Lewis acid is found to accelerate the rate enormously. In these electrophilic substitutions it seems highly probable that the the activation involves the pi electron system of the benzene ring. Olivier studied the reaction sequence ... 

Of about 40 dioxygenases known up to date, more than 80% have iron built into their structure or require added iron for full activity. Cleavage of the benzene rings is a function that appears to depend almost entirely on nonheme iron-containing dioxygenases. 

The 13C chemical shifts of the parent compound were assigned by comparison with the spectrum of cinnamic acid (see Section 4.11.2) and from the knowledge that for benzenoid methine carbons introduction of an acyloxy function into the benzene ring causes small shifts of the meta carbons, and shifts the signals of the para carbons to higher field, while the ortho carbons become even more shielded (Fig. 5.16) [635]. 

To all rules, there are always exceptions. These have been made to allow unexpected natural isoquinolines that just happen to present unexpected substituents that nature for some reason chose to contribute to this collection. Mention has been made of an occasional carbonyl group disrupting the aromaticity of the benzene ring (this is the basis of the quinonic isoquinolines). The nitrogen atom (position 2) occasionally displays an amide group (these have been entered at the fourth letter of the structural alphabet). Several natural compounds demand a hydroxyl or methoxyl function at the isoquinoline 3- or 4-positions. When this occurs, the compound is listed as a footnote under the parent structure. 

Simple phenolics are substituted phenols. The ortho, meta and para nomenclature refers to a 1,2-, 1,3- and 1,4-substitution pattern of the benzene ring, respectively, where in this case one of the functional groups is the hydroxyl group. With three functional groups, the substitution pattern can be 1,3,5, which, when all three substituents are identical, is designated as a mt /fl-tri-substitution pattern, whereas the 1,2,6, substitution pattern is indicated by the prefix v/c (Figure 1-1). 

Fig. 6.12. A Typical CARS signal trajectory revealing the particle number fluctuations of 110-nm polystyrene spheres undergoing free Brownian diffusion in water. The epi-detected CARS contrast arises from the breathing vibration of the benzene rings at 1003cm 1. B Measured CARS intensity autocorrelation function for an aqueous suspension of 200-nm polystyrene spheres at a Raman shift of 3050 cm-1 where aromatic C-H stretch vibrations reside. The corresponding translational diffusion time, td, of 20 ms is indicated. (Panel B courtesy of Andreas Zumbusch, adapted from [162])...

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