Aromatic compounds, fused acids

A clever application of this reaction has recently been carried out to achieve a high yield synthesis of arene oxides and other dihydroaromatic, as well as aromatic, compounds. Fused-ring /3-lactones, such as 1-substituted 5-bromo-7-oxabicyclo[4.2.0]oct-2-en-8-ones (32) can be readily prepared by bromolactonization of 1,4-dihydrobenzoic acids (obtainable by Birch reduction of benzoic acids) (75JOC2843). After suitable transformation of substituents, mild heating of the lactone results in decarboxylation and formation of aromatic derivatives which would often be difficult to make otherwise. An example is the synthesis of the arene oxide (33) shown (78JA352, 78JA353). 

The aromatic core or framework of many aromatic compounds is relatively resistant to alkylperoxy radicals and inert under the usual autoxidation conditions (2). Consequentiy, even somewhat exotic aromatic acids are resistant to further oxidation this makes it possible to consider alkylaromatic LPO as a selective means of producing fine chemicals (206). Such products may include multifimctional aromatic acids, acids with fused rings, acids with rings linked by carbon—carbon bonds, or through ether, carbonyl, or other linkages (279—287). The products may even be phenoUc if the phenoUc hydroxyl is first esterified (288,289). 

The accepted configuration of naphthalene, ie, two fused benzene rings sharing two common carbon atoms in the ortho position, was estabUshed in 1869 and was based on its oxidation product, phthaUc acid (1). Based on its fused-ring configuration, naphthalene is the first member in a class of aromatic compounds with condensed nuclei. Naphthalene is a resonance hybrid ... 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

Simple uncharged six-membered aromatic heterocycles cannot contain a divalent heteroatom. The azines are numbered to indicate the relative positions of the nitrogen atoms. 1,2,3,4-Tetrazine, pentazine and hexazine are unknown, however, a number of fused 1,2,3,4-tetrazines, primarily A -oxides and A -aryl quaternary salts, are known, but of monocycUc compounds, only a few di-A -oxides have been prepared. Of the other systems, 1,2,3,5-tetrazine is unknown, although theoretically it could be moderately stable, but fused derivatives include the drug temozolomide (see 33.7). Derivatives of 1,3,5-triazine are very well known and available in large quantities, indeed they are amongst the oldest known heterocycles the trioxy-compound ( cyanuric acid ) was first prepared in 1776 by Scheele by the pyrolysis of uric acid. 

Pyrrole, furan, and thiophene are aromatic compounds that undergo electrophilic aromatic substitution reactions preferendally at C-2. These compounds are more reactive than benzene toward electrophiles. When pyrrole is protonated, its aromahcity is destroyed. Pyrrole polymerizes in strongly acidic solutions. Indole, benzofuran, and benzothiophene are aromatic compounds that contain a five-membered aromatic ring fused to a benzene ring. 

The same conclusion has been reached as a result of the study of aromatic compounds. A noteworthy example of a case in which the method fails is furnished by the three isomeric bromoben-zenesulphonic acids. The ortho, meta, and para compounds, when fused with sodium hydroxide, yield the same dihydroxy derivative of benzene, resorcinol, which has been shown to be a meta compound. On account of such facts as this, a definite conclusion as to structure can not be reached by the study of a single transformation. The problem is not so difficult as it appears to be, on account of the fact that the exhaustive study of many transformations has shown clearly that those of certain types take place normally. Such transformations are the ones employed in the determination of structure. 

Although the original Blanc procedure using paraformaldehyde (sometimes called tri-oxymethylene) and fused and pulverized zinc chloride is followed in many preparations, this reaction has been modified by using either 85% phosphoric acid as catalyst or ZnCh as catalyst but with AlCl or NiCl as cocatalyst. In addition, 40% formaldehyde has been used for this reaction instead of paraformaldehyde. Bromomethylation of aromatic compounds could be considered another modification. ... 

The same methodology applies to heteroarylpentenes which lead to heterocyclic compounds fused with a cyclohexane (cyclopentane fused-heterocycles are not available since the five-membered ring closure onto the aromatic is too slow to compete with the oxidative elimination) (equation (64)) [128]. Even though the reactions are usually performed under thermal conditions in aqueous acetic acid at 90 °C, it has been shown to proceed faster under sonication, although in slightly lower yields. 

Kantlehner et reported the formylation of (hetero)aromatic compounds including unsubstituted and alkyl-substituted aromatics, aromatic ethers, tertiary aromatic amines, fused aromatic rings and thiophenes using new formylating agents (Scheme 1.1) based on formamide derivatives in the presence of Lewis acids. 

Synthesis of Heterocyclic Compounds. Thionyl chloride and pyridine at elevated temperatures convert diarylalkenes, styrenes, and cinnamic acids to benzo[i>]thiophenes and adipic acid to 2,5-bis(chlorocarbonyl)thiophene. Additional heterocycles which have been prepared include thiazolo[3,2-a]indol-3(2//)-ones, oxazolo[5,4- /]pyrimidines, and 1,2,3-thiadiazoles. Treatment of 1,2-diamino aromatic compounds with thionyl chloride gives good yields of fused 1,2,5-thiadiazoles. ... 

Aromatic nitriles (or aryl cyanides) can be obtained by methods (1) and (3). but not by method (2). In addition, aromatic nitriles can be prepared by two other methods, (a) from the corresponding diazo compound by Sandmeyer s Reaction (p. 189), (b) by fusing the corresponding sulphonic acid (or its salts)... 

The extensive examinations of aromatic heterocvcles, such as benzoxa-zines, benzothiazines, and quinazolines, and the corresponding oxo derivatives may also have been due to the fact that the starting materials of the syntheses of these hetero compounds, such as salicylic acid or anthranilic acid and their derivatives, have been industrial products since the end of the nineteenth century. In contrast, the starting materials for the stereospecific syntheses of the related cycloalkane-fused heterocycles can generally be prepared only with some difficulty and did not become available commercially until more recently [90MI1, 91MI1 92ACH(129)107]. 

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