Heteroatom heterocycles Seven-membered

The only heterocyclic seven-membered ring system with maximum unsaturation containing six heteroatoms is 1,3A4,5,2,4,6-trithiatriazepine (1). The methoxycarbonyl derivative 2 is a minor product (14%) of the complex reaction of tetrasulfur tetranitride with dimethyl acetylenedicarboxylatc in refluxing toluene, which gives mainly dimethyl l,2,5-thiadiazole-3,4-dicarboxylate (3, 67%) (see Houben-Wcyl, Vol. E8d, pl54ff which includes an experimental procedure). Two other products are the trithiadiazepine 4 (5%, see Section 4.4.1.1.1.) and the 1,2,4-thiadiazole derivative 5 (3%).385... 

Dipolarophiles utilized in these cycloadditions leading to five-membered heterocycles contain either double or triple bonds between two carbon atoms, a carbon atom and a heteroatom, or two heteroatoms. These are shown in Scheme 9 listed in approximate order of decreasing activity from left to right. Small rings containing a double bond (either C=C or C=N) are also effective dipolarophiles, but these result in six- and seven-membered ring systems. 

Fully saturated seven-membered heterocycles with one or two heteroatoms are normally in mobile twist-chair conformations (Section 5.17.1.1, Chapter 5.18) (b-77SH(2)123). Annelation and the introduction of exocyclic double bonds can have profound effects oxepan-2-one, for example, is in a near chair conformation (67JA5646). 

The NMR spectra of heterocyclic compounds with seven or more ring members are as diverse as the shape, size and degree of unsaturation of the compounds. NMR is perhaps the most important physical method to ascertain the structure, especially the conformational statics and dynamics, of large heterocycles. Proton-proton coupling constants provide a wealth of data on the shape of the molecules, while chemical shift data, heteroatom-proton coupling constants and heteronuclear spectra give information of the electronic structure. Details are found in Chapters 5.16-5.22. Some data on seven-membered rings are included in Table 10. 

Chemistry of furazanes fused with six- and seven-membered heterocycles with one heteroatom 99UK154. 

The scope for further developments in the chemistry of seven-membered heterocyclic systems is considerable, particularly with respect to multi-heteroatom component systems. New synthetic methods are needed for these systems and ring-fused derivatives. The demand for such systems is likely to be largely driven by the search for structurally novel drug leads. 

It is also possible to construct seven-membered aromatic heterocycles with a jr-electron decet if the heteroatoms have sufficient electronegativity to produce seven bonding orbitals with 10 jr-electrons, as in compounds of type 209 (Scheme 79). For thio derivative 209 (X = S, Scheme 79), lH NMR data show deshielded NH protons compared to the system with X = CH2, a fact which was explained by aromatic delocalization.249... 

Fig. 3.10 Six-membered heterocycles with two heteroatoms obtained by solid-phase chemistry. Seven-membered heterocycles...

The non-planar polyene nature of azepines renders them susceptible to a variety of intra-and inter-molecular pericyclic processes. The azepine-benzeneimine valence isomerization has been discussed in Section 5.16.2.4, and the ring contractions of azepines to benzenoid compounds in the presence of electrophiles is covered in Section 5.16.3.3. In this section the thermal and photochemical ring contractions of azepines to bicyclic systems, their dimerizations and their isomerizations via sigmatropic hydrogen shifts are discussed. Noteworthy is a recent comprehensive review which compares and contrasts the many and varied valence isomerizations, dimerizations and cycloadditions of heteroepins (conjugated seven-membered heterocycles) containing one, two and three heteroatoms (81H(15)1569). 

Chapter 5.18 presents over 50 heterocyclic systems whose chemistry usually depends more on the nature of the heteroatoms than on the systems being seven-membered heterocycles. At the present state of knowledge, organizing the chapter in separate sections on structure, reactivity and synthesis would not produce a happy result, especially for the reactivity section. Little is presently known about the reactivities of the majority of the systems, many of which have been prepared to explore their pharmacological activities. The chapter, therefore, has been organized according to the number and nature of the heteroatoms. 

The transition metal catalyzed synthesis of seven membered and larger heterocycles attracted considerably less attention than the preparation of their five and six membered analogues. Typical examples in this chapter include the formation of heterocycles in insertion reactions, or through carbon-heteroatom bond formation. Although the formation of some macrocyclic natural products was also achieved in cross-coupling reactions they will not be discussed in detail. 

Formation of five-membered ring systems (1,2-addition) can compete with formation of the seven-membered heterocycles (1,4-addition). If the first step of the reaction sequence, namely the nucleophilic attack of the terminal heteroatom of the diene, is hindered by steric or electronic effects, the five-membered ring product is formed exclusively. 

Seven-membered heterocycles containing at least two heteroatoms ... 

VI. Compounds from Seven-Membered Ring Heterocycles Containing Only Nitrogen as Heteroatom... 

G. Peri-Heterocycles with Seven-Membered Heteroring and Single Heteroatom... 

Heterocyclization of two-carbon one-heteroatom synthon with two-carbon two-heteroatom synthon is the most common approach to the synthesis of monocyclic and fused seven-membered heterocycles with 1,3,5-heteroatoms. These reactions can be further subdivided to substitution and addition reactions. 

The second method employed for the synthesis of telluraxanthene is similar to that widely used for the preparation of various tricyclic heterocycles containing one or two heteroatoms. It is based on the interaction of 2,2 -dilithiodiphenylmethane with powdered tellurium, by which reaction telluraxanthene 82 has been prepared in 50% yield [81JOM(205)167]. The reaction apparently proceeds through the intermediate bis(telluro-phenolate) 86 which is oxidized to the heterocyclic ditelluride 87. The latter compound eliminates tellurium from its stericaily strained seven-membered ring and converts to telluraxanthene. This mechanistic scheme seems to be corroborated by the observation that the treatment of lithi-oarenes ArLi usually ends in the formation of diarylditellurides Ar2Te2 (74MI1 83MI2). 

When the methoxyarene rings are tethered by carbon-heteroatom chains, as in 104, such oxidations proceed in intramolecular fashion and afford the benzo-annulated seven-membered heterocycles 105 (Scheme 33) (96CC1481, 98JOC7698, 01T345). Selected coupling reactions of the types shown in Schemes 32 and 33 have also been demonstrated with the polystyrene analogs of BTIB and DAIB (01T345). 

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