Benzo thiophene analogs

Benzo[6]thiophene-2,3-dicarboxylic anhydride reacts with phenol and resorcinol, respectively, to yield the benzo[ >]thiophene analogs of phenolphthalein and fluorescein.625... 

In the past several years a number of reports have appeared describing cardiovascular and diuretic effects associated with benzo[Z>]thiophene derivatives. Among these was the study of the benzo[ ]thiophene analog (371) of the/3-adrenergic blocking agent propanolol, which is the a-naphthol ether. The compounds showed comparable activity, showing that benzo[ ]thiophene may function as a bioisostere of naphthalene also. 

The pKa values for the four readily available thienopyridines (258-261) have been determined (Table 9). As can be seen from these data, the isoquinoline analogs are stronger bases than the quinoline analogs the same is true for isoquinoline and quinoline. The UV data of the benzo[6]thiophene analogs (258-261) (Table 10) show a considerable similarity to that of quinoline (258, 261) and isoquinoline (259,260). As expected, the spectra of thieno-[3,4-6]- and -[3,4-c]-pyridine differ from the parent compounds the colors of (262) and (263) are probably due to their long-wavelength maxima. 

Benzo[6]thienylketones are reduced by lithium aluminum hydride to secondary alcohols.465, 526 The carbinol bases of a series of benzo-[6]thiophene analogs of malachite green have been prepared.621... 

The harmala alkaloids harmaline (368 X = NH) and harmine (369 X = NH) are active reversible inhibitors of monoamine oxidase (MAO). Benzo[Z> ]thiophene analogs of harmaline (368 X = S) and harmine (369 X = S), when tested in vitro as inhibitors of rat liver MAO, showed that (368 X = S) was 50 times more potent than harmaline, but (369 X = NH or S) were equivalent in potency. The replacement of the indolic nitrogen by sulfur greatly increased the lipid solubility of the molecule, which was reflected in the physiological disposition of the two analogs. 

Benzo[b]thiophene analogs 111 (R1 = H, 5- or 6-R2) of substituted tryptophans have been prepared by reaction of a 5- or 6-substituted 3-chloromethylbenzo[i>]thiophene with diethyl acetamido- or formamido-malonate, and hydrolysis of the product.456,472,473 Corresponding a-methyl derivatives (111, R1 = Me) may be obtained by the hydantoin route (Eq. 3).47 2... 

The corresponding benzo-analogs (IH-indole, benzofuran, and benzo-thiophene), however, react preferentially via the C3-position. This can be rationahzed by the Wheland intermediates originating from electrophilic substitution on the C2- and C3-position. For the latter, one more resonance structure can be drawn without loss of aromaticity of the annulated benzene ring (Figure 4). C2-functionalization is less favored but can take place when the C3-position is blocked for instance (either via direct attack at C2 or via initial attack at C3 followed by 1,2-migration). 

Furan and thiophene have also been utilized in this type of transformation as building blocks. In the same maimer, prerequisite structures prepared by cross-coupling as well as traditional carbanion addition were converted expectedly into benzo- and dibenzofurans and their thiophene analogs (i.e., 47 48) [80]. Likewise, sesquiterpene furanoquinone 51 was synthesized [81], and the total synthesis of the indohzidine alkaloid, septicine 54, was performed with the key step 52 -> 53 for the pyrrole case [82] (Scheme 9). 

Startg. diazosulfoxide and a little Rh(OAc)2 refluxed in benzene until reaction complete - product. Y 78%. F.e. incl. benzo[5]thiophene analog s. C.J. Moody et al.. Tetrahedron Letters 29, 6009-12 (1988). 

The detailed structure of the clathrate compound formed between 2,5,5-trimethylhex-3-yn-2-ol and 4-p hydroxyphenyl-2,2,4-trimethylthio> chroman has been determined by A -ray crystallography. tra/i5 -3,4-Dibromothiochroman and analogous dibromo-naphthothio-pyrans, prepared by addition of bromine to the appropriate A -thio-chromenes, may exist in sofa conformations. The dibromo-compounds undergo ring-contraction reactions with alkalis, yielding benzo[ ]thiophen derivatives. ... 

Polybenzofc] thiophene (or Polyisothianaphthene). Benzo[c]thio-phene—in the field of conducting polymers most commonly known as isothianaphthene—is a compound that is very sensitive toward oxidation and whose chemical properties are drastically different from its thiophene analogs [594-598]. As a consequence, the manipulation of isothianaphthene is not straightforward. The preparation of isothianaphthene is well established [596,599,600]. Synthesis of a sterically protected isothianaphthene compound has been reported [601]. 

The use of free-radical reactions for this mode of ring formation has received rather more attention. The preparation of benzo[Z)]thiophenes by pyrolysis of styryl sulfoxides or styryl sulfides undoubtedly proceeds via formation of styrylthiyl radicals and their subsequent intramolecular substitution (Scheme 18a) (75CC704). An analogous example involving an amino radical is provided by the conversion of iV-chloro-iV-methylphenylethylamine to iV-methylindoline on treatment with iron(II) sulfate in concentrated sulfuric acid (Scheme 18b)(66TL2531). 

Whereas the degradation of the carboxylates of the monocyclic furan, thiophene, and pyrrole is initiated by hydroxylation, degradation of their benzo analogs is generally carried out by dioxygenation. The degradation of the analogs dibenzofuran and dibenzo-[l,4]-dioxin is discussed in Part 2 of this chapter. 

The [2 + 2] photodimerization of a, j8-unsaturated sulfones is correctly viewed as a photoreaction of alkenes, rather than the sulfone group, and this aspect has been reviewed recently by Reid, as part of a wider survey of the photoreaction of O- and S-heterocycles. The topic continues to attract considerable interest and a few recent examples, as well as some synthetic applications, will be discussed here. Much of the photodimerization work has been carried out on the benzo[fc]thiophene (thianaphthene) 1,1-dioxide system. For example. Porter and coworkers have shown that both 3-carboxybenzo[i]thiophene 1,1-dioxide (65) and its methyl ester give only the head-to-head (hth), anti dimer (66) on irradiation in ethanol. In a rather unusual finding for such systems, the same dimer was obtained on thermal dimerization of 65. Similar findings for a much wider variety of 3-substituted benzo[fi]thiophene 1,1-dioxides have been reported more recently by Geneste and coworkers . In the 2-substituted analogs, the hth dimer is accompanied by some of the head-to-tail (htt), anti dimer. The formation of the major dimer appears to proceed by way of an excited triplet and the regiochemistry observed is in accord with frontier MO theory. 

Electron-withdrawing substituents seem to stabilize the benzo[cjfuran system as they do in the analogous benzo[c]thiophene and benzo [c]indole series. l-Cyano-3-phenylbenzo[c]furan (128) was obtained from the aldehyde 127 as stable yellow needles hydrolysis with base yields the carboxylic acid (129). Catalyzed hydrogenation of these cornpounds leads to 1,3-dihydrobenzo[c]furans (130, R = CH2NH2, COOH = Ph). Increased... 

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