Bridgehead Nitrogen Ring Systems

Adachi, K. Nomura, and K. Mitsuhashi, Chem. Pharm. BiiH., 1976, 24, 85. 

3-diaza-, 1,3-oxaza- and 1,3-thiaza-heterocycles, in which the starting material has an alpha hydrogen adjacent to the heteroatom which can readily be abstracted on irradiation.  

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Reports concerning bridgehead nitrogen bicyclic systems containing four extra heteroatoms (3 1) are rare <1996CHEC-II(8)729>. Only four such ring systems, 1-4, have been reported previously. Related ring systems reported in the last decade are l,2-dihydropyrimido[l,2- ]-l,2,4,5-tetrazin-6-ones 5, 67/-[l,2,4,5]tetrazino[3,2- ] quinazolin-6-ones 6, thioxotetrazinoquinazoline 7, and pyrimido[l,2- ]-l,2,4,5-tetrazin-6-ones 8. 

Ring systems with bridgehead nitrogen atoms are excluded throughout. 

This chapter reviews bicyclic 6-6 ring systems containing one bridgehead nitrogen atom and one extra heteroatom,... 

Of the possible 10 bicyclic systems containing one bridgehead nitrogen and two extra nitrogen atoms, 1 1 in each ring, nine are known. One new system, pyrimido[l,6-A]pyridazine (system 1 in Table 1), has been reported since CHEC-II(1996) <1996CHEC-II(8)633>. The number of known tricyclic benzo-fused systems is 16. 

There are 12 isomeric structures for this ring system, where the triazine ring is directly fused to the pyrimidine nucleus of the quinazoline ring one of the nitrogen atoms of the quinazoline ring is located at the bridgehead of the bicyclic ring. 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

The number of methods available for the synthesis of bicyclic systems containing two fused five-membered rings with one bridgehead nitrogen can be summarized in a few general reactions dehydrative ring closure, oxidative Schiff base cyclization, and base-induced closure (Scheme 3). One-pot reactions involving precursor synthesis followed by cyclization are also known. 

Cyclopenta[c]pyridylaminomethylenemalonate (1063) was cyclized by the action of a mixture of acetic anhydride and concentrated sulfuric acid at 90°C for 1 hr to give the tricyclic nitrogen bridgehead ring system (1064, R = CN) in 60% yield (83 KGS 1279). 

Quinuclidine (1) is a saturated bicyclic system with a bridgehead nitrogen atom. It has, in contrast to tertiary aliphatic amines and -substituted piperidines, a rigid structure. The atoms forming the quinuclidine ring are incapable of changing their relative positions by rotation around bond axes. These bond axes are included in the bicyclic system with each ring in the boat form. 

Pyrido[ 1,2-a]py rimidines represent a simple bicyclic ring system that contains a nitrogen-bridgehead condensed pyrimidine moiety. Synthetic methods for these compounds can often be applied to the preparation of similar bi- and polycyclic ring systems (e.g., benzologs, N-analogs, five membered congeners, and so on) and their reactivities are sometimes similar to those of the above-mentioned derivatives. 

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