Rings containing Several Nitrogens

Miscellaneous Rings containing Several Nitrogens.—From 4,5-diamino-benzo[A]thiophen and its 3-methyl derivative, the ring system (620) was obtained by condensation with 9,10-phenanthrenequinone, and the system 

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In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

Even more complex is the stmcture of a hepatitis C protease inhibitor called BILN 2061, which has a 15-membered ring containing two nitrogen atoms (4.55). Olefin metathesis was used in the final step of its synthesis to close the ring of generalized intermediate 4.54 where several different R groups were used (Scheme 4.63). ... 

Several blocked diamines or amino-alcohols are commercially available. The aldimine is an aldehyde-blocked diamine. The ketimine is a ketone-blocked diamine. The oxazolidine is a five-membered ring containing oxygen and nitrogen. The oxazolidine ring shown below is an aldehyde-blocked amino alcohol. The basic synthetic concepts of an aldimine, a ketimine, and an oxazolidine are shown below ... 

The third chapter of this volume is concerned with mono- and diazaquinones. S. R dl (Prague, Czech Republic) reviews compounds that contain one nitrogen or two nitrogen atoms directly within the quinonoid ring, a subject that has not been previously summarized in a comprehensive manner. This is in distinction to the several specialized reviews of quinones themselves. Heterocyclic quinones, in the sense of compounds in which the quinonoid ring is fused to a heterocyclic ring, were covered in Volume 45 of our series in 1989. 

Cyclizations at moderate to low dilution. A series of A-tosylated (tosyl = p-toluenesulphonyl Ts) macrocycles may be readily prepared by direct means starting from pre-tosylated reactants (Richman Atkins, 1974). Equation [2.3] summarizes an example of this useful reaction type. Reasonable yields (often considerably better than 50%) of such cyclic tosylated products may be achieved in spite of the fact that such reactions are usually performed at moderate dilution. A number of procedures exist for detosylation of these products to yield the corresponding rings containing only secondary nitrogens a common method has been to treat the tosylated intermediate with hot concentrated sulfuric acid for several days. 

The structural formulas of several cyclic compounds containing both nitrogen and sulfur are shown in Figure 17.4. Basic to the structures of these compounds is the simple ring structure of thiazole. It is a colorless liquid (bp, 117°C). One of its major uses has been for the manufacture of sulfathiazole, one of the oldest of the sulfonamide class of antibacterial drugs. The use of sulfathiazole is now confined to the practice of veterinary medicine because of its serious side effects. 

We have analyzed (14J the molecular structures of these semirigid chiral ligands and, in both, we have identified a common chiral pharmacophore, namely a phenyl ring and a nitrogen atom, uniquely juxtapositioned one to the other, which is contained in an extended phenethylamine moiety. We have since shown that the same pharmacophore is present in the DAR antagonist (+)-octo-clothepin,III,as well as in several other DAR ligands (19). 

Helerocycles. The review cited summarizes reactions of hydrazoic acid leading to heterocycles containing several ring nitrogens. 

A purine base contains one pyrimidine and one imidazole ring connected via a shared (C4-C5) aromatic bond. One nitrogen atom in the purine base is generally protonated. Due to the presence of several nitrogen sites, several tautomers usually co-exist both in solution and in the solid state. The populations of individual tautomers are strongly influenced by the substitution of the piuine base, the temperature, the pH, the solvent, and the salt concentration. 

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