Indoles, benzofurans and benzothiophenes

Analogous compounds derived by fusion of a benzene ring to a pyrrole furan or thio phene nucleus are called indole benzofuran and benzothiophene... 

In this paper, the selectivity of the ECH method for the reduction of nitro compounds to the corresponding amines on RCu electrodes will be compared with that of reduction by RCu alloy powder in alkaline aqueous ethanol. In the latter method (termed chemical catalytic hydrogenation (CCH)), chemisorbed hydrogen is generated in situ but by reduction of water by aluminium (by leaching of the alloy) (equation [12]). The reductions by in situ leaching must be carried out in a basic medium in order to ensure the conversion of insoluble Al(OH)3 into soluble aluminate (equation [12]). The selectivity and efficiency of the electrochemical reduction of 5-nitro-indoles, -benzofurane, and -benzothiophene at RCu electrodes in neutral and alkaline aqueous ethanol will also be compared with that of the classical reduction with zinc in acidic medium. 

Although not fitting exactly into the scope of this book, the iridium catalyzed borylation of five membered heterocycles through C-H bond activation also deserves mentioning. A recent report by Miyaura disclosed the reaction of bis(pinacolato)diboron with heteroaromatic systems, where thiophene, fiirane and pyrrole were converted to their 2-boryl derivatives with good selectivity (6.86.), The yields presented refer to the diboron compound since the heterocycles were used in excess in all cases. Indole, benzofurane and benzothiophene were monoborylated with similar efficiency.116... 

Equilibrium and rate constants for the keto-enol tautomerization of 3-hydroxy-indoles and -pyrroles are collected in Table 32 (86TL3275). The pyrroles ketonize substantially (103-104 times) faster than their sulfur or oxygen analogues, and faster still than the benzo-fused systems, indole, benzofuran, and benzothiophene. The rate of ketonization of the hydroxy-thiophenes and -benzothiophenes in acetonitrile-water (9 1) is as follows 2-hydroxybenzo[b]thiophene > 2,5-dihydroxythiophene > 2-hydroxythiophene > 3-hydroxybenzo[/ Jthiophene > 3-hydroxythiophene. 3-Hydroxythiophene does not ketonize readily in the above solvent system, but in 1 1 acetonitrile-water, it ketonizes 6.5 times slower than 2-hydroxythiophene (87PAC1577). 

Our aromaticity-determining reactions for the three heterocycles are endothermic by 70, 40, and 48 kJ mol-1, to be compared with the exothermicity for the corresponding carbocycle, indene, of nearly 9 kJ mol-1. Indole, benzofuran, and benzothiophene are truly aromatic species in terms of thermochemical stabilization. 

Equilibrium and rate constants for the keto-enol tautomerization of hydroxy heterocycles are summarized in Table 38 <1986TL3275>. The pyrroles ketonize (i.e., 226 — 230) substantially faster (103-104 times) than their sulfur or oxygen analogues, and still faster than the benzo-fused systems (indole, benzofuran, and benzothiophene). 

If the heteroatom contributes two electrons to the tr-electronic structure of the molecule (e.g., nitrogen in pyrrole or indole, oxygen in furan, sulfur in thiophene), it essentially represents a charge-transfer donor-type substituent. Its effect on the electronic structure and spectra will be dominated by its ability to donate electrons and to a lesser extent by considerations of electronegativity. Thus, the interactions of nitrogen, oxygen, and sulfur in, say, indole, benzofuran, and benzothiophene, with their aromatic systems, are similar to the interactions of amino, hydroxy, and mercapto exocyclic groups with their aromatic systems. 

The ASE values correlate with magnetic susceptibility for the five-membered heteroaromatic compounds. Magnetic and polarizability criteria put the order of aromaticity as thiophene > pyrrole > furan. The other criteria of aromaticity discussed in Section 8.2 are also applicable to heterocyclic compounds. HOMO-LUMO gaps and Fukui functions (see Topic 1.5) have been calculated for compounds such as indole, benzofuran, and benzothiophene and are in accord with the known reactivity patterns of these heterocycles. 

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. 

Scheme 58 Pd-catalyzed regioselective C—H alkenylation of IH-indoles (a) and Ru-catalyzed C—H alkenylation of IH-indole, benzofuran, and benzothiophene (b) directed by a removable carboxylate group.

The benzo-fiised counterparts of the simple heterocycles pyrrole, fiiran, and thiophene are indole, benzofuran, and benzothiophene. These compoimds are related to the two-ring, all-carbon aromatic compound naphthalene ... 

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