Cyclazines

The cyclazines (a trivial name) are tricyclic fused molecules containing a central bridgehead nitrogen and a peripheral 7r-system. The definition of aromaticity in these compounds is not as straightforward as for the simple bicyclic molecules discussed above, and a more detailed analysis of the molecular orbitals may be required. 

Cyclazines can be prepared by cyclisation of bicyclic precursors, for example (3.2.2.)cyclazine is prepared via a cycloaddition reaction on indolizine (Section 25.1.1), or by cyclocondensation. 

In contrast, (3.3.3)cyclazine has no aromatic resonance stabilisation and is unstable and highly reactive, displaying some diradical character. However, its hexa-aza analogue is extremely stable, this stabilisation being attributed to perturbation of the molecular orbitals by the electronegative atoms leading to a much 

Suggest a structure for the final, monocyclic product of the following sequence quinolizinium bromide with LiAlH4 and then H2/Pd giving C9H13N. 

Write down the structures of the intermediates in the following synthesis of the quinolizinium cation 2-methylpyridine was reacted with LDA, then Et0(CH2)2CH=0 to give C11H17NO2, which was heated with HI ( C9Hi2NO 1) this salt was then heated with AC2O (-H CgHjoN I ) and this finally heated with Pd-C to afford quinolizinium iodide. 

Isoelectronic replacement of a carbanionic carbon by a hetero atom gives much more stable compounds such 5,5-bicyclic aromatic systems have received considerable attention pyrrolo[2,l-b]thiazole is one such example. Although we have not had sufficient space to describe these in this short chapter, their properties and synthesis follow the general principles discussed for example, imidazothiazoles are prepared from substituted thiazoles in a way analogous to the preparation of imidazopyridines, from substituted pyridines. 

1 Heterocyclic systems with bridgehead nitrogen atoms in The Chemistry of Heterocyclic Compounds , Vol. 15, Ed. Mosby, W. L., Series Ed. Weissberger, A., Wiley-Interscience, 1961 Special topics in heterocyclic chemistry in The Chemistry of Heterocyclic Compounds , Vol. 30, Series Eds Weissberger, A. and Taylor, E. C., Wiley-Interscience, 1977. 

---

Heteroeyeles structurally based on the phenalene ring system form an interesting elass, frequently possessing distinetive eolours. With nitrogen as the central atom we have the unstable 9b-azaphenalene (24), whieh has only fairly reeently been prepared and is still comparatively little studied (76JCS(Pl)34l). The cyclazine nomenclature is commonly applied to this and related compounds thus, (24) is (3.3.3)cyclazine. With further aza substitution, in positions alternant to the central atom, their stability increases the heptaazaphenalene (25) is (thermally) a very inert compound, derivatives of which, e.g. the triamine, have been known since the early days of organic chemistry (see Chapter 2.20). 

Cyclohexyl[l 5]crown-5, potassium complex equilibrium constant, 7, 742 (73MI52101) Cyclohexyl[15]crown-5, sodium complex equilibrium constant, 7, 742 (73MI52101) Cycloocta[ 1,2-c 5,6-c ]difuran H NMR. 4. 564 (70JA973) Cyclopenta[h][2.2.4]cyclazine... 

Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

Indolizine, 3-benzoyl-6-bromo- l-(2-pyridyl)-structure, 4, 445 In4olizine, 3-chloro-synthesis, 4, 470 Indolizine, 3-cyano-cyclazine synthesis from, 4, 460 Indolizine, 8-cyano-synthesis, 4, 469... 

Thiabicyclo[3.1.0]hex-3-ene synthesis, 4, 784 9-Thiabicyclo[3.3.1]nonane 9,9-dioxide bond angles, 7, 409 5-Thiabicyclo-2-pentene, 1,2,3,4-tetrakis(trifiuoromethyl)-rearrangement, 7, 153 2H-l,2-Thiaborin dibenzo fused, 1, 658 1-Thia[2.2.2]cyclazines, 4, 479 5-Thia[2.3.3]cyclazines, 4, 481 Thiacyclobutadienes — see lH-1 A -Thietes... 

Similarly, methyl propiolate and methyl phenylpropiolate give the cyclazine (67) and its 2-phenyl derivative, respectively, as would be expected of reactions initiated through a Michael addition to the acetylenic ester. 

---