Five-membered nitrogen heterocycle

Under microwave irradiation several azaheterocycles (i.e. pyrrole, imidazole, indole and carbazole) can react remarkably fast with alkyl halides to give, exclusively, N-al-kyl derivatives (Eqs. 32 and 33) [45, 46]. Such reactions have been performed simply by mixing an azaheterocycle compound with 50% excess alkyl halide and a catalytic amount of TBAB. The reactants were absorbed either on a mixture of potassium carbonate and potassium hydroxide or on potassium carbonate alone and then irradiated in a domestic microwave oven for 30 s-10 min. 

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As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

In the case of five-membered nitrogen heterocycles, the fused systems are frequently referred to as azaazulenes" [see 81H(I5)547, 8IYGK690]. 

The reliability of semi-empirical methods (AM 1, PM3, and MNDO) for the treatment of tautomeric equilibria has been tested in a series of five-membered nitrogen heterocycles, including... 

The reliability of semi-empirical methods (AMI, PM3, and MNDO) for the treatment of tautomeric equilibria has been tested for a series of five-membered nitrogen heterocycles, including 1,2,3-triazole and benzotriazole. The known tendency of MNDO to overestimate the stability of heterocycles with two or more adjacent pyridine-like lone pairs is also present in AMI and to a somewhat lesser extent in PM3. Tautomers with a different number of adjacent pyridine-like nitrogens cannot be adequately treated by these semi-empirical methods. Both AMI and PM3 represent major improvements over MNDO in the case of lactam-lactim tautomerism. The stability of N-oxides as compared to N-hydroxy tautomers is overestimated by PM3 method. All three methods give reliable ionization potentials and dipole moments (90ZN(A)1328). 

A variety of five-membered nitrogen heterocycles can be prepared efficiently by inter- or intramolecular addition/cyclizations of sulfonamide anions with alkynyliodonium salts. The intermolecular variant employs the combination of the amides 172 or anilides 174 with propynyl(phenyl)iodonium triflate (Scheme 65) [131,132]. The yield of dihydropyrroles 173 in this cyclization is extremely sensitive to the nature of the protective group P the tosyl group in 172 proved... 

Grandberg and A. N. Kost, in Lecture Summaries for a Conference on the Chemistry of Five-membered Nitrogenous Heterocyclic Compounds, p. 23. Rostov-on-Don. 1962. 

Pyrrole is about 1014 times weaker as a base than is pyrrolidine, the five-membered nitrogen heterocycle that has no double bonds, because the basic pair of electrons on the nitrogen of pyrrolidine is not part of an aromatic cycle. 

The reactive part of haemoglobin is a porphyrin. These are aromatic molecules with 18 electrons around a conjugated ring formed from four molecules of a five-membered nitrogen heterocycle. Chemically, symmetrical porphyrins are easily made from pyrrole and an aldehyde. 

Interaction of 258 with anilines or five-membered nitrogen heterocycles produced 265 and 266 via an aminoalkylation . Bicyclic derivatives 267-271 with an aminal structure resulted from the interaction of 258 with amides, urethanes, imides, ureas, amines or hydrazines. Finally, 272 was formed with carbon acids and a reduction to 273 occurred with the sodium salt of formic acid " . It is not yet totally clear whether an iminium ion is involved in the formation of 259-273. The yields of isolated products varied from 45 to 95 %. 

An -carbonyi radicai cyciization was the key step in C.-K. Sha s enantioselective total synthesis of the alkaloid (-)-dendrobine. The five-membered nitrogen heterocycle was installed during the final stages of the synthetic effort. The bicyclic azido alcohol intermediate was oxidized using the Jones reagent to give the corresponding azido ketone, which was converted in three steps to the natural product. 

In the synthesis of 3-demethoxyerythratidinone, an erythrina alkaloid, the key step is the construction of a five-membered nitrogen heterocycle via stereoselective ns annulation The tributyltin hydride mediated radical cyclization of a dopamine dimethyl ether derivative 13 affords the diastereomer 14 with the required configuration in excellent yield. Through a three-step sequence the missing double bond is constructed to give the desired product. 

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