Heterocycles furan derivatives

Recently, many transformations of various heterocycles into pyridazines have been reported. From the synthetic point of view it appears that furan derivatives are the most valuable. 

The wide variation in the entropy factors for both the substituted phenyl and heterocyclic compounds and in particular for the methoxyphenyl and furan derivatives was considered to be strong evidence for solvent effects being predominant in determining the activation entropy. Consequently, discussion of the substituent effects in terms of electronic factors alone requires caution in this reaction. Caution is also needed since rates for the substituted phenyl compounds were only determined over a 20 °C range. The significance of entropy factors has also been indicated by the poor correlation of the data of the electrophilic reactivities of the heterocyclic compounds, as derived from protodemercuration, with the data for other electrophilic substitutions and related reactions572. 

Tricyclic dithiine derivatives of tetrathiafulvalene (TTF) 32 have been prepared for their increased electropolymerization potential <2000CC1005>. The effect of different tricyclic heterocycles upon the redox properties of TTF analogues was explored, and showed that the furan derivative 33 had an unusual nonplanar conformation that allowed for the attainment of higher oxidation states at relatively low oxidation potentials <2004JMC2822>. 

The synthesis of oxygen heterocycles in which cyclization onto a pendant alkyne is a key step has also been achieved. Reaction (7.36) shows an example of iodoacetal 29 cyclization at low temperature that afforded the expected furanic derivative in moderate Z selectivity [47]. A nice example of Lewis acid complexation which assists the radical cyclization is given by aluminium tris(2,6-diphenyl phenoxide) (ATPH) [48]. The (3-iodoether 30 can be com-plexed by 2 equiv of ATPH, which has a very important template effect, facilitating the subsequent radical intramolecular addition and orienting the (TMS)3SiH approach from one face. The result is the formation of cyclization products with Z selectivity and in quantitative yield (Reaction 7.37). 

Marcaccini S, Pepino R, Marcos CF, Polo C, Torroba T (2000) Studies on isocyanides and related compounds. Synthesis of furan derivatives and their transformation into indole derivatives. J Heterocycl Chem 37 1501-1503... 

The chemistry of fiiians and benzofurans was a Held of lively research in the last year. There are a number of reasons for this activity. The furan ring system - both in its native as well as in its reduced form - occurs in a great number of natural products and a wide variety of these compounds has been isolated from natural sources. This subject is treated regularly with care and accuracy in Heterocycles and will not be repeated here. Therefore only a few examples will be given in this chapter. Several new furan derivatives were isolated from natural sources (-)-wistarin 1 from the marine sponge Ircinia sp. <99TA3869>,... 

Volume 26 contains three chapters. C.A. Ramsden reviews heterocyclic betaines derived from six-membered heteroaromatic rings. These compounds have been intensively studied over the past 10 years and have not previously been comprehensively reviewed. O. Meth-Cohn and B. Tamowski summarize the chemistry of the thiocoumarins, a somewhat neglected group of heterocycles. Finally, W. Friedrichsen has reviewed the chemistry of the benzo[c]furans which, unlike the aza and thia analogs, have not previously been considered in this series. Here again we have a group of compounds the chemistry of which has advanced considerably over the last decade. 

The five-membered aromatic heterocycles pyrrole (5), furan (6) and thiophene (7) are formally derived from cyclopentadienyl anion by replacement of one CH group with NH, O or S, each of which can contribute two p-electrons to the aromatic ir-electron sextet. Heteroatoms of this type have in classical structures only single bonds and are called pyrrole-like . Other five-membered aromatic heterocycles are derived from compounds (5), (6) and (7) by further replacement of CH groups with N, 0+ or S+. 

Despite its unfavorable NMR properties, the nO nucleus has attracted considerable interest, since its chemical shifts represent a discriminating probe for structural and molecular properties. In a study of some 5-membered heterocycles (furan and isoxazole methyl derivatives) (840MR(22)55) it was found that the nO chemical shifts are mainly determined by the p-electron density on the oxygen atom. A nO downfield shift of 222 ppm is observed on the formal aromatization of tetrahydrofuran to furan (61HCA865). 

Furans, thiophenes and pyrroles have all been obtained by addition of alkyne dienophiles to a variety of other five-membered heterocycles, as illustrated in Scheme 64 (see also Sections 3.4.1.9.1 and 4.2.3.3.4). As the alkyne moiety provides carbons 3 and 4 of the resulting heterocycle, this synthetic approach provides an attractive way of introducing carbonyl-containing substituents at these positions, especially as many of the heterocyclic substrates are readily available. Even furans can be converted into other furan derivatives by this method (Scheme 65) (85JHC1233,87BSF131). 

On condensation of peri-hydroxynaphthaldehydes with the Fischer base (82KGS1501) or with 1,3,3-trimethylisobenzofurylium perchlorate (86DOK639), 2-substituted heterocyclic 2//-naphtho[6c]furan derivatives... 

The photochemistry of heterocyclic compounds was the object of a book published in 1976 and edited by Buchardt (76MI1). Here, the photochemistry of thiophene covers eight pages written by Lablache-Combier (76MI123). Some reviews have appeared since on the photochemical behavior of pyrrole and furan derivatives (89G419 96H(43)1305 96H(43) 1529) but apparently none on thiophene photochemistry. 

When the pentamer (66) reacts with alkoxide anions at low temperatures (-30 to -40°C), then the products of kinetic control (102) are isolated, whereas at higher temperatures, thermodynamic control prevails and the products (103) are obtained [131,132] (Scheme 68). Similar observations have been made with sulphur nucleophiles [132], and complex products are obtained with amines, including the formation of heterocycles [132]. Reaction of (66) with ethyl acetoacetate gave a pyran derivative (104) in a reaction that may be rationalised as shown in Scheme 69 [133]. In an analogous way.furan derivatives are formed from perfluoro-2-butene and -cyclohexene in base-induced reaction with 1,3-dicarbonyl derivatives [133]. 

The direct electrochemical methoxylation of furan derivatives represents another technically relevant alkoxylation process. Anodic treatment of furan (14) in an undivided cell provides 2,5-dimethoxy-2,5-dihydrofuran (15). This particular product represents a twofold protected 1,4-dialdehyde and is commonly used as a C4 building block for the synthesis of N-heterocycles in life and material science. The industrial electroorganic processes employ graphite electrodes and sodium bromide which acts both as supporting electrolyte and mediator [60]. The same electrolysis of 14 can be carried out on BDD electrodes, but no mediator is required The conversion is performed with 8% furan in MeOH, 3% Bu4N+BF4, at 15 °C and 10 A/dm2. When 1.5 F/mol were applied, 15 is obtained in 75% yield with more or less quantitative current efficiency. Treatment with 2.3 F/mol is rendered by 84% chemical yield for 15 and a current efficiency of 84% [61, 62]. In contrast to the mediated process, furan is anodically oxidized in the initial step and subsequently methanol enters the scene (Scheme 7). 

Under similar conditions diazo acetoacetate does not afford cyclopropanes but dihydrofurans as 62 which can be aromatized (e.g. to 63)20). A different furan derivative 64 is obtained from ethyl diazopyruvate as outlined in Eq. 19 38). Possibly cyclopropanes are intermediates in these reactions, which rearrange to the five-membered heterocycles under the conditions employed. 

Naturally Occurring Furan Derivatives The mass spectra of naturally occurring oxygen heterocyclics were reviewed only recently.52... 

It has been known for a considerable time that furan derivatives can be converted into a large number of different compounds. Only the reactions which have been carried out recently will be described in detail. The conversion of furan derivatives into other heterocyclic systems is usually expected when the labile oxygen system is transformed into a more stable heterocycle. 

The benzo[f]furan derivative 64 has been shown to be only marginally diatropic, another indication of furan being the least aromatic of the simple five-membered heterocycles <1996JOC935>. 

While the furan containing complexes of ligands of type have attracted the most attention, other ostensibly related furan-derived ligand systems have also been considered as being likely to provide complexes of interest [49]. For instance, macrocycles which contain more than one type of heterocycle have been reported... 

Facile cleavage of a saturated heterocycle in an oligomerization process is peculiar to furan derivatives. Thus, the structure of the 2-methylfuran "tetramer" 9 has only three furan rings (74BCJ1467). 

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