Ring systems 348 Subject

A large amount of data are available on the C spectra of saturated six-membered ring systems. The subject has been reviewed in detail by Eliel and Pietrusziewicz (79MI20101). 

The benzofuroxtin [benzofurazan oxide, 3,4-benzo-l,2,6-oxa-diazole-2-oxide, or 2,1,3-benzoxadiazole-l-oxide (1)] ring system has been reviewed briefly on several occasions, notably by Kaufman and Picard,Boyer, and Behr. The mqst recent of these covers the literature until 1959, and since that date there have been many advances in the subject. This, we feel, justifies the field being covered once more, and its separation from the monocyclic 1,2,5-oxadiazole oxides—the furoxans. We consider also other furoxano-fused compounds in this chapter, subject to the limitation that the ring adjacent to the furoxan is aromatic and six-membered. 

Great progress has been made in the experimental and theoretical investigation of tautomerism of five-membered ring systems since 1975, and a number of reviews dealing partly or entirely with this subject have appeared since then. In Table I some pertinent references are given. 

Tlie first two chapters in this volume continue the survey of heteroaromatic tautomerism that was the topic of Volume 76 of Advances in Heterocyclic Chemistry. Tliis whole subject was first dealt with comprehensively in Volumes 1 and 2 of our series, which date back to 1963 and 1964.Tlie area was updated in a special supplementary volume of the series that appeared in 1976 but is now seriously out of date. Tire chapters in Volume 76 deal with a general introduction and the tautomerism of tive-membered monocyclic rings systems. 

The chemistry of furazans and furoxans has been the subject of intensive investigations over the years. There has been been a substantial increase in synthetic manipulations of substituents attached to these ring systems. Additionally, there are a number of publications that deal with the incorporation of the heterocyclic rings into more complex molecules. It is the aim of this review to present new synthetic developments and to update reviews in the field of... 

Various reviews dealing with the 1,2.4-triazines have been published. The most recent is that published by Neunhoeffer and Wiley (78HC749) covering the literature through 1974. Owing to the increase of the number of publications on the 1,2,4-triazines, a survey of the literature on their condensed ring systems with three- to five-membered heterocycles, from 1974 through 1992, constitutes the subject of this review. 

Along with each index (annual, semiannual, or collective) appears an index of ring systems. This valuable index enables the user to ascertain immediately if any ring system appears in the corresponding subject or chemical substance index and under what names. Eor example, someone wishing to determine whether any compounds containing this ring system... 

The pharmacological activity of the 1,5-benzothiazepine derivative diltiazem has given further impetus for synthetic routes to this ring system. A traditional preparation of the intermediate 62 by the reaction sequence shown in Scheme 12 has been subject to microwave studies, when the final product was obtained as a mixture of isomers <96TL6413>. Under optimised conditions irradiation in toluene at 390 watts for 20 minutes gave mainly the cis-isomer as the main product (cis/trans 9 1) in 75% yield. However, reaction at 490 watts in the presence of acetic acid resulted in a reversal of this ratio and a yield of 84%. The... 

A thiepin is formally isoelectronic with the 8ic-electron 1,3,5,7-cyclooctatetraene and 1,3,5-cycloheptatrienide ion and, if planar, may actually be antiaromatic. Recently, the question of the antiaromaticity of thiepin has been the subject of interest for both synthetic and theoretical chemists. The apparent instability of the thiepin ring system is in good agreement with theoretical calculations. Dewar and Trinajstic 68) have reported that the thiepin is considered to be weakly antiaromatic (RE = — 1.45 kcal mol-1) based on PPP SCF MO calculations. On the other hand, Hess Jr. and Schaad 69) have found it to be substantially antiaromatic (RE = —0.232 J) by using the Huckel MO method. This result was also supported by a graph-theoretical treatment by Aihara 70). 

These ring systems are systematically discussed as primary subjects in CHEC-II(1996), where the earlier general reviews are also enumerated <1996CHEC-II(8)563>. Since then, the chemistry of these ring systems has been summarized in two main reviews covering the literature up to 2001 <2003AHC(84)219, 2003AHC( 85) 173 >. 

Although the number of potential molecules to be made is quite large, the number of small aromatic ring systems is much smaller. A recent study identified 24,847 such ring systems and found that only 1701 have been synthesized. The remaining were subjected to synthetic feasibility calculations and more than 3000 additional ring systems were identified (Figure 3) that have never been made [26]. 

In the course of studies on azide-tetrazole equilibria, some azido derivatives 73 of this ring system have been subjected to X-ray structure elucidation <2005JST(751)65>. These derivatives proved to be mainly planar and the least planar part of these molecules were the azide moieties. In both cases (72 R= H and Me), formation of hydrates were also observed. Crystallographic analysis of the trifluoromethyl compound was described by Lange et al. <1997APH299>, and structure elucidation of the nucleoside analogue 74 was reported by Stanovnik et al. <1998JHC513>. 

Relatively few new papers have appeared on synthetic procedures for the title ring system. Some of these follow established methodologies. Thus, three reports appeared where 2-hydrazinopyrazines - or their derivatives - were subjected to ring closure to give [l,2,4]triazolo[4,3- ]pyrazines. These products - with yields and references - are shown in Table 14. 

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

Electrophilic substitution at the anthraquinone ring system is difficult due to deactivation (electron withdrawal) by the carbonyl groups. Although the 1-position in anthraquinone is rather more susceptible to electrophilic attack than is the 2-position, as indicated by jt-electron localisation energies [4], direct sulphonation with oleum produces the 2-sulphonic acid (6.3). The severity of the reaction conditions ensures that the thermodynamically favoured 2-isomer, which is not subject to steric hindrance from an adjacent carbonyl group, is formed. However, the more synthetically useful 1-isomer (6.7) can be obtained by sulphonation of anthraquinone in the presence of a mercury(II) salt (Scheme 6.4). It appears that mercuration first takes place at the 1-position followed by displacement. Some disulphonation occurs, leading to the formation of the 2,6- and 2,7- or the 1,5- and 1,8-disulphonic acids, respectively. Separation of the various compounds can be achieved without too much difficulty. Sulphonation of anthraquinone derivatives is also of some importance. 

An appendix systematically lists references to reactions of dialkylalkoxy-malonates with amines, including not only the common aliphatic and aromatic amines, but also a very wide variety of heterocyclic amines classified according to ring system. The appendix also provides systematic references to the different ring systems obtained by ring closure of the dialkylaminomethylenemalonates. The appendix should be used in conjunction with the subject index a separate subject index is provided for this monograph volume. 

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