Five-membered nitrogen

Arguing that the MNDO method is more suitable than the AMI method for predicting the heats of formation of five-membered nitrogenated aromatic rings, Garcia and Vilarrasa (88H1803) calculated that 4-fluoroimidazole 14a (R = F, = H) is 2.5 kJ mol more stable than its tautomer 14b,... 

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. 

Figure 15.9 Pyrrole and imidazole are five-membered, nitrogen-containing heterocycles but have six tt electron arrangements, much like that of the cyclopentadienyl anion. Both have a lone pair of electrons on nitrogen in a p orbital perpendicular to the ring.

Thiamin, or vitamin Blf contains a positively charged five-membered nitrogen-sulfur heterocycle called a thiazoliwn ring. Explain why thethiazolium ring is aromatic. 

Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

Miscellaneous Syntheses Starting from a Five-Membered Nitrogen-Containing Ring... 

Table 2.21. Preparation of five-membered, nitrogen-containing heterocycles by rearrangement of chromium-carbene-derived ammonium ylides.

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

Based on the observation that the majority of secondary amines shown to be effective in iminium ion catalysed transformations were cyclic five-membered nitrogen containing heterocycles, it was postulated that a highly nucleophilic nitrogen was central to catalytic activity [44]. This proposal was reinforced by the discovery that secondary amines with a-heteroatoms (a-effect nucleophiles) provided an effective platform for the acceleration of iminium ion catalysed... 

B. Three-Membered and Five-Membered Nitrogen and Phosphorus Rings. 388... 

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). 

The formation of pyrrole and its benzo analogs from other heterocyclic systems can occur in any of several general ways. In this section we will consider reactions which change the ring size and composition. In Section 3.06.6, reactions where the five-membered nitrogen-containing ring remains intact will be considered. 

N.-Y. Shih, R. Aslanian, A. Lupo, J. J. Piwinski, M. J. Green and A. K. Ganguly, Imidazolyl or Imidazolylalkyl Substituted with a Four or Five Membered Nitrogen Containing Heterocyclic Ring, PCT Int. Patent Appl. WO 93/12108 (1993). 

The most usable and well-known pathway for the synthesis of five-membered nitrogen-containing heterocycles is condensation involving a,P-usaturated carbonyls and 1,2-binucleophilic compounds, e.g., derivatives of hydrazine and hydroxylamine (Scheme 2.8). The procedure based on these reactions was successfully applied for a long period [45, 46, 47, 48, 49, 50, 51, 52, 53]. 

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... 

In the series of stable five-membered nitrogen-containing heterocycles, tetrazole possesses extreme characteristics that are inferior only to those of pentazole (cf. Section 6.07.4.3). Attention should be paid to the obvious fact that, in contrast to the hypothetical pentazole, tetrazole is a thermodynamically stable compound. This heterocycle surpasses the simple azide and hydrazoic acid by a number of key tests. However, tetrazoles are thermodynamically stable in the condensed phase, relatively weakly sensitive to impact and friction, and not very toxic, unlike HN3 which is notorious for its high sensitivity to impact, friction, thermal and electric impulses, and toxicity <1999THS(3)467>. 

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. 

In a study of synthetic routes to the phorbol class of compounds, Lautens cyclised the stannane 307 (with 5 equiv MeLi, to avoid stannane reincorporation) to the 7,5-fused ring system 3 0 8.138 This reaction also works in the synthesis of analogous saturated five-membered nitrogen and sulfur heterocycles (see below). 

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. 

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