Heteroatom-substituted aromatic compounds

The reagent potassium nitrosodisulfonate (33), known as Fremy s salt, was first prepared in 1845. Its use as a chemoselective oxidizing agent has been reviewed extensively by Zimmer [59a] and Parker [59b] and will only be mentioned briefly here. While it is most widely known for its use in the oxidation of various heteroatom-substituted aromatic compounds to quinones [59], it has also been used in the selective oxidation of benzylic alcohols to ketones [60] and the oxidation of a-amino and a-hydroxy acids to a-keto acids [61]. 

Therefore, the estimation of rate constants for the PAH (including for anthracene) is now uncertain. For substituted PAH, we can estimate approximately the enhancement of the rate constant over that for the parent PAH by using the correlation between the rate constant and Xa+ discussed above for the monocyclic aromatic compounds (Atkinson, 1987), with the enhancement factor being e134 o+. This approach also may work for heteroatom-containing aromatic compounds, such as pyridines and triazines. 

Reaction of nucleophiles with the polarized N=C bond of azines proceeds via dearomatization and formation of the corresponding 1,2-adduct. With alkyllithiums, for example, it is possible to isolate the dihydro products by careful neutralization of the reaction mixtures these are, in general, rather unstable, however, and can easily be reoxidized to the fully aromatic compounds (Scheme 4). The dihydro adducts formed in these direct nucleophilic addition reactions can also be utilized for the introduction of substituent groups /3 to the heteroatom. Thus, reaction of (35) with one of a number of electrophiles, followed by oxidation of the intermediate dihydro product, constitutes a simple and, in many cases, effective method for the introduction of substituent groups at both the 2- and 5-positions of the pyridine ring (Scheme 4). Use of LAH in this sequence, of course, results in the formation of 3-substituted pyridines. 

Aromatic compounds substituted by a heteroatom can be oxidized to corresponding quinone derivatives using hypervalent iodine reagents. Phenols can be oxidized either in the ortho [84] or in the para position [85] by using iodine(III) reagents. By this route, benzothiazoles of type 36, Scheme 17, are accessible and they have been tested as antitumor compounds [86,87]. 

According to this procedure, with proper choice of reaction conditions, a sizeable amount of diphenylacetylene can be converted quantitatively to triphenyteyclopropenium bromide in a few hours. The reaction is of wide generality and can be applied to p-anisylphenylacetylene and to di-p-anisylacetylene, or with p-anisal chloride instead of a,a-dichlorotoluene. to prepare p-methoxy derivatives of the title compound.2 Since the initial preparation of this derivative of the cyclopropenyl cation by a less efficient procedure,3 many aryl-, alkyl- and heteroatom-substituted derivatives of this simplest cyclic aromatic system have been synthesized,4 including... 

Strong nucleophiles such as organolithium or organomagnesium derivatives do not react with substituted or unsubstituted phosphabenzene or arsabenzene (Y = P or As) by nucleophilic substitution as in the case of pyridines, but by addition to the heteroatom forming intermediate anions. These anions can then be converted into non-aromatic compounds by reaction with water yielding 1-alkyl-1,2-dihydro-derivatives, or they can be alkylated by an alkyl halide with the same or a different alkyl group, when two products may result a l,2-dialkyl-l,2-dihydro-derivative, or a 2 -derivative (Figure 17). The former products are kinetically controlled, whereas the latter compounds are thermodynamically controlled. 

Benzene is the archetypal example of a compound that displays aromatic properties. Aromatic compounds are characterised by a special stability over and above that which would be expected as a result of the delocalisation of the double bonds in a linear system. Typically, this extra stability is associated with the closed loop of six electrons, the aromatic sextet, as occurs in benzene itself. However, larger and smaller loops are possible. So long as there are (4n+2)7i electrons (where n is an integer from zero, upwards) present in (at least three) adjacent p sub-orbitals that form a closed circuit, then the resultant molecule will be aromatic. It is also possible for heteroatoms to form part of the cyclic structure, and for the structure to be charged. Furthermore, aromatic compounds, in contrast to unsaturated compounds, tend to undergo substitution reactions more readily than addition reactions. This is because it is usually thermodynamically favourable to preserve the aromatic stability rather than release the energy contained in the double bonds. 

There is, for example, no end-of-text chapter entitled Heterocyclic Compounds. Rather, heteroatoms are defined in Chapter 1 and nonaromatic heterocyclic compounds introduced in Chapter 3 heterocyclic aromatic compounds are included in Chapter 11, and their electrophilic and nucleophilic aromatic substitution reactions described in Chapters 12 and 23, respectively. Heterocyclic compounds appear in numerous ways throughout the text and the biological role of two classes of them—the purines and pyrimidines—features prominently in the discussion of nucleic acids in Chapter 27. 

Among a number of oxime ether derivatives of 1 with aromatic and aliphatic substitutions, the compounds bearing heteroatoms in substituents, such as nitrogen, oxygen, and sulfur, exhibited a significant increase in activity in vivo. Based on their in vitro and in vivo activities against staphylococci and streptococci as well as their pharmacokinetics, five compounds 18 and 23 through 26 have been selected (Table I) [6]. 

Cyclic ketones with a fused aromatic ring usually form chloroenals without side reaction, as in the case of compounds 112 and heteroatom-substituted analogs such as compounds 113 (Eq. 101) 2-indanone gives the iminium compound 114 (Eq. 102). ... 

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