1 - heteroarene

Alkyl groups attached to aromatic rings are oxidized more readily than the ring in alkaline media. Complete oxidation to benzoic acids usually occurs with nonspecific oxidants such as KMnO, but activated tertiary carbon atoms can be oxidized to the corresponding alcohols (R. Stewart, 1965 D. Arndt, 1975). With mercury(ll) acetate, allyiic and benzylic oxidations are aJso possible. It is most widely used in the mild dehydrogenation of tertiary amines to give, enamines or heteroarenes (M. Shamma, 1970 H. Arzoumanian. 1971 A. Friedrich, 1975). 

The alkaloid dubamine contains a single bond between the two heteroarene units. This lond was formed in 79% yield by the generally valuable palladium-catalyzed eoupling of an ryltrimethylstannane with an aryl triflate (see section 1.6). The requisite stannane was pre-ared from l,3-benzodioxol-5-yl triflate and hexamethyldistannane with the same palladium atalyst, the triflate ester was obtained from 2(1 f/)-quinolinone and trifluoromethanesulfonic jihydride (A.M. Echavarren, 1987). An earlier attempt to perform this aryl coupling by dassical means gave a yield of only 1 %. 

Under different conditions [PdfOAcj2, K2CO3, flu4NBr, NMP], the 1 3 coupling product 86 with 4-aryl-9,10-dihydrophenanthrene units was obtained. The product 86 was transformed into a variety of polycyclic aromatic compounds such as 87 and 88[83], The polycyclic heteroarene-annulated cyclopen-tadicnc 90 is prepared by the coupling of 3-iodopyridine and dicyclopentadiene (89), followed by retro-Diels Alder reaction on thermolysis[84]. 

M A K O S Z A Vicarious nucleoptiiHc substitution Synthesis of akyl substituted hetsrocydss by vicai1ous nucleophilic substitution ol hydrogen in heteroarenes, nitrodenvatives ol heleroarenes. 

In this chapter we discuss only the physical structure of arene- and heteroarene-diazonium ions and salts. The chemical reactions of diazonium ions and the chemical structures of the products will be the subject of later chapters. 

Scheme 16 Angular versus linear benzannulation of (dibenzo)heteroarenes...

Elektronenreiche Carboxy-N-heteroarene erleichtern ebenfalls die Hydrogenolyse (anwesende Alkoxycarbonyl- bzw. Formyl- oder Acyl-Gruppen werden mitreduziert). Pyrrol-carbonsauren werden z. B. durch Lithiumalanat in Diathylather oder THF zu den entsprechenden Methyl-pyrrolen reduziert4 s z, B.4 ... 

Zur Herstellung N-substituierter aromatischer bzw. heteroaromatischer Amine geht man man vom Amino-aren bzw, -heteroaren und Orthocarbonsaure-triestern aus3 z. B. ... 

FIGURE 3.1 Bacterial oxygenation systems (excluding cytochrome P450 systems). (From Neilson, A.H. and Allard, A.-S. Microbial metabolism of PAHs and heteroarenes, The Handbook of Environmental Chemistry, Vol. 3J, pp. 1-80, Springer, 1998. With permission.)... 

It is clear from the preceding comments that there is no absolute distinction between the oxygenase activities mediated by dioxygenases. This is even less clear for heteroarenes than it is for carbocyclic compounds. An illustrative example is provided by Pseudomonas putida strain 86 in which 8-hydroxy-quinol-2-one is produced from quinol-2-one (Rosche et al. 1997). 

These oxidoreductases are widely used for the introduction of the oxygen atom from HjO into heteroarenes, especially azaarenes including pyridine, quinoline, pyrimidine, and purine, and they generally contain molybdenum. 

The degradation of the live-membered heteroarenes furan-2-carboxylate and pyrrole-2-carboxylate is initiated by the corresponding hydroxylases (Hormann and Andreesen 1991 Koenig and... 

Boyd DR, ND Sharma, R Boyle, RAS McMordie, J Chuna, H Dalton (1992) A h NMR method for the determination of enantiomeric excess and absolute configuration of ciT-dihydrodiol metabolites of polycyclic arenes and heteroarenes. Tetrahedron Lett 33 1241-1244. 

Neilson AH, A-S Allard (1998) Microbial metabolism of PAHs and heteroarenes. Handb Environ Chem 31 1-80. 

The direct arylation of heteroaryls is particularly attractive due to the fact that these moieties are present in many biologically active compounds [58], Recently, etinkaya and co-workers reported the direct arylation of benzoxazoles and ben-zothiazoles with aryl bromides catalysed by a bis-NHC-palladium complex [59], Also, Sames and co-workers have described the C-H arylation of different SEM-protected heteroarenes, catalysed by NHC-Pd complex 28 (Scheme 7.12, pathway a) [60],... 

Kiener, A. (1992) Enzymic oxidation of methyl groups in heteroarenes a versatile method for the preparation of heteroaromatic carborylic acids. Angewandte Chemie-International Edition, 31 (6), 774—775. 

The arylation of electron-rich arenes, such as azulene (55)206 and heteroarenes, has been sporadically described. Under similar conditions phenols undergo arylation, which is preferably directed at the ort/zo-positions, probably due to the involvement of palladium phenolate intermediates.188,207 Polysubstitution occurs readily.208 The para-position can be attacked only with the sterically hindered 2,6-di-t-butylphenol.209 Similar ortho-diarylation of arenes bearing carbonyl groups (acetophenone, anthrone, benzanilide, etc.) shows that the or//zo-di reeling effect of the substituent is more important than its other electronic effects.189... 

A versatile and regioselective synthesis of benzo[b]furans, naphthalenes, indoles and benzothiophenes was achieved by reaction of o-alkynylarene and heteroarene carboxaldehyde derivatives in the presence of iodonium ions. The reaction mechanism was also discussed <06CEJ5790>. 

A cobalt-catalyzed method for arylation of heteroarenes including thiazole and benzothiazole was reported in 2003 <030L3607>. According to this report, the direct C-5 arylation of thiazole with iodobenzene was carried out in the presence of cobalt catalyst [Co(OAc)2/IMes] and cesium carbonate, and a complete reversal of arylation from C-5 to C-2 was observed with the bimetallic Co/Cu/IMes system. This report has been retracted as the laboratory of the senior author has not been able to reproduce the key results disclosed in the communication <06OL2899>. 

The introduction of sulfur between two ortho amino groups is the oldest and still the most commonly used route to benzo- and heteroarene-fused 1,2,5-thiadiazoles. The reaction has been extensively reviewed in both CHECK 1984) and CHEG-II(1996). The in situ preparation of Ar-sulfinylanilinc via /3-elimination of chloroform from trichlorometh-anesulfinamides 200 was recently supported by trapping with 1,2-benzenediamine to give the benzothiadiazole 2 in 85% yield (Equation 43) <1997TL487>. 

A useful strategy for the formation of fused thiadiazoles is the annulation of suitably functionalized 1,2,5-thiadiazoles. Common routes involve the use of 3,4-difluoro-l,2,5-thiadiazole, 3,4-diamino-1,2,5-thiadiazole, l,2,5-thiadiazole-3,4-dicarbonyls, l,2,5-thiadiazole-3,4-dicarbonitrile, amino-1,2,5-thiadiazole-3-carboxamides and carboxamidines. These afford heteroarene-fused 1,2,5-thiadiazoles (which are covered in Volume 9). Below follows a brief description of fused thiadiazoles that fall within the scope of this chapter. 

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