Five Ring Nitrogen Systems

Five Ring Nitrogen Systems.—Pynolines and Pyrrolidines. Ketene dithioacetals react with aziridines to give vinyl aziridines which undergo an iodine catalysed rearrangement to pyrrolines yields are high (Scheme 61). The novel spiro-com-pound (172) has been obtained by this route. A hetero-vinyl cyclopropane... 

Fused Five and Six Ring Nitrogen Systems.—The acid catalysed reactions of alkyli-dene bisurethanes with conjugated dienes gave various azacyclic and azabicyclic molecules formed by 1,4 (or 1,6)-addition to the conjugated system by the acylimine (241). > In new work the first example of a formal 1,3-cycIoaddition during the reaction of (241) with dienes has been observed (Scheme 107). 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

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. 

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). 

The fused heterocyclic rings to be discussed here have normally been produced by an intramolecular cyclization of an N(6)-, N(2)- or S-substituent onto a ring nitrogen atom in the purine nucleus and are mainly five- or six-membered systems cyclonucleosides such as (210) are of course notable exceptions and a few miscellaneous examples exist. 

As noted previously, arylamines are generally less basic than alkylamines. Anilinium ion has pKg = 4.63, for instance, whereas methylammonium ion has piCg = 10.64. Arylamines are less basic than alkylamines because the nitrogen lone-pair electrons are delocalized by interaction with the aromatic ring electron system and are less available for bonding to H. In resonance terms, arylamines are stabilized relative to alkylamines because of their five resonance forms. 

In systems which contain more than two hetero atoms in the same ring we find the trends in properties, which this book has described, taken to further extremes. In particular, the additional hetero atoms, in both six- and five-mem-bered systems, lead to a suppression of electrophilic substitution and a slowing of electrophilic addition to nitrogen. On the other hand, further increases in tendencies for nucleophilic substitution and addition, and in the five-membered compounds, further increases in acidities of A -hydrogen are shown. 

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