Polyheterocyclic systems

Among polyheterocyclic systems, coumarins are synthesized by many routes, including the Pechmann reaction, which involves condensation of phenols with /fke-toesters [51]. This reaction, which has been the most widely applied method, has re-... 

The purpose of this section is to highlight the applications of microwave irradiation to multistep synthesis of polyheterocyclic systems with potent pharmaceutical value. When conventional thermal procedures (metal or oil bath) fail, and irrespective of the conditions needed in the homogeneous phase, microwave irradiation can be used as an alternative to classical methods enabling development of easy and rapid access to new heterocycles. 

Using nitrile oxides, various compounds and materials possessing valuable properties have been prepared. Among them are thin-film resistors useful for a thermal head and comprising a nitrile oxide, ruthenium and oxygen, a method for manufacturing the resistor by coating or deposition (529), isoxazole and/or isoxazoline polyheterocyclic systems like 458, which are useful for development of a new class of ionophores (530). 

This methodology was further developed in an elegant manner by Padwa and coworkers (61). Combined with a subsequent desulfurization reaction, the method was successfully applied toward the synthesis of complex polyheterocyclic systems related to alkaloid skeletons. For example, the reaction of 94, obtained from... 

Recently, interest in the syntheses of polyheterocyclic systems containing fused l,3-thiazin-4-ones has been growing due to the search of new biologically active substances. The synthetic methods used for obtaining these compounds are the same as those used for benzo-TAs. 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

Applying the versatility of the cobalt-catalyzed pyridine formation (eq. (2)), Vollhardt [45] has varied the basic reaction extensively. Using rather sophisticated alkyne and nitrile precursors with 77 -Cp-cobalt dicarbonyl as the catalyst, the preparation of a number of polyheterocyclic systems having physiological interest was brought about. Using eq. (14) a synthetic route to the isoquino[2,l-(7] [2,6]naphthyridine nucleus (eq. (16)) was developed [46]. 

The parent system (28, R = H) serves as a building block, e.g. for polyheterocyclic systems (see p 474). It is commercially produced by a modified Hofmann degradation of phthalimide. 

Among polyheterocyclic systems, coumarins are synthesized by many routes, including the Pechmann reaction [51], which involves condensation of phenols with yS-ketoesters. This reaction, which has been the most widely applied method, has recently been studied under the action of MW irradiation by several authors [52], including the GS-MW process for 4-substituted 7-aminocoumarins [53]. Synthesis of methyl 7-aminocoumarin-4-carboxylates (51 and 52) by the Pechmann reaction involves heating a mixture of m-aminophenol and dimethyl oxalate at 130 °C (Scheme 9.17). Under such conditions, however, the yield of the reaction is variable, usually low (36%). Use of graphite as a support led to the expected lactone in slightly better yield (44%). 

Polyheterocyclic systems have been efEdently synthesized by cyclocondensation between anthranilic add and lactim ethers derived from 2,5-piperazinediones. This reaction leads to pyrazino[2,l-b]quinazoline-3,6-diones. When applied to bis(lactim) ethers the procedure again works better under the action of microwaves, with reaction times reduced from hours to minutes and enhancement of yields [232]. 

The most practically important compound from oxepanes is e-caprolactone which is used as a monomer. Other oxepanes are considered following their structures from rather simple monocyclic to complicated polyheterocyclic systems. 

Nitroarenes [77-79] and nitrohetarenes [80] have been used, instead of nitroalkenes, in similar cyclizations providing an access to fused pyrrole derivatives, isoindoles, and other polyheterocyclic systems. 

Thiophene oligomers received recent attention, becuase of their non-linear optical properties. Detailed structural investigations in this new topic can really help to clarify the complex phenomena, which govern fast optical response in polyheterocyclic systems. Unfortunately, efforts to obtain single crystals of these compounds have been unsuccessful, so it is necessary to undertake powder diffraction analysis. 

Isoxazole-isoxazoline polyheterocyclic systems have been synthesized for applications as ionophores using resin boimd alkenes/alkynes as dipo-larophiles. For instance, the isoxazole possessing an alkene moiety 41 was reacted with a nitrile oxide, generated from nitroalkane 13d imder Mukaiyama conditions, to afford isoxazoline 42 in high yield (Scheme 12) [ 104]. 

The specific and general names of the fragment of ihe analogous pair are given in this textual field. For the sake of brevity and to ease searching, numberings, indicators of the degree of saturation, and, for polyheterocyclic systems, fusion descriptors are typically omitted. For heterocycles, both the trivial and systematic... 

MSubstituted-2-pyridones can be used as substrates for ring closure to a number of polyheterocyclic systems, as an alternate to the Pschorr cycliza-tion Of to the cyclizations of the corresponding At-alkyl-2-halopyridinium halides. 2-Substituted pyridines (MI-625 X =C1, Br, OC Hj) and 3-(2-bromo-ethyl)indole give -[2-(3-indolyl)ethyl]-2-substituted pyridinium bromide... 

Fused Systems containing Thiazole.—A large number of polyheterocyclic systems have been prepared, but in most cases the methods of synthesis, and the properties of the products, are straightforward extensions of earlier work they will not, therefore, be further discussed. 

Turning away from benzazepines, routes to thienazepines, pyridazepines, and many other fused polyheterocyclic systems are available through thermolysis of JV-heteroaromatic-2-vinyl aziridines (420). ° The aziridines were prepared by the method of Scheiner, though two of them were found to rearrange spontaneously to the azepines (421). 

By integrating the polyacetylene moiety into a polyheterocyclic system, the electron donating function of N or S ring atoms stabilizes the conjugated system, especially in the doped, positively charged highly conductive state (bipolaron state). 

---