The Ring System

9-methylpurine (4b) spectra. A further and significant difference between the two pairs of purines is seen following protonation in that the first MCD bands of the 1- and 3-methyI derivatives are blue shifted (15-20 nm) whereas a red displacement (6-10 nm) occurs with the 7- and 9-methyl analogs. In addition, protonation alters peak intensities and the variation can be used to identify a particular isomer. Thus, while the band due to 3-methylpurine undergoes a 3-fold intensification, the 1-methyl analog suffers only a 0.25-fold 

2-position [Eq. (1)]. Other examples of this type of ring fission induced by nucleophilic attack are known.  

This important aspect of purine structure is still of active interest. Theoretical and practical studies have been carried out to ascertain the site of 

Further support for the existence in solution of near equal amounts of the 7H and 9H protomers of purine is provided by carbon-13 resonance data in which the disposition of the acidic proton can be correlated with the magnitude of the shift changes of the C-4 and C-5 bridgehead atoms. Use of the 7- and 9- methyl homologs as reference compounds and extrapolation of the results to the 7H and 9H purines by applying a- and j -substituent parameter corrections gives 40% for the 7H tautomer in dimethyl sulfoxide and an estimate of 58% in water. Data obtained from a temperature-jump relaxation technique used to study the rapid kinetics of 7H 9H prototropy of adenine in aqueous solution has given values for the equilibrium constant K = C7H/C9H = 0.28 at 20°) and the 7H isomer population ( 22%). This 

Although the protomer distribution values for the latter are at variance with those obtained from UV spectral studies, no rationale to account for 

Bergmann, D. Lichtenberg, U. Reichman, and Z. Neiman, Jerusalem Symp. Quant. Chem. Biochem. 6, 397 (1974). 

Albert, Heterocyclic Chemistry, 2nd Ed. Oxford Univ. Press, (Athlone), London and New York, 1968. 

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Hetero)cyclic hydrocarbons Ln.J T.n.J L beginning of a carbocyclic ring T beginning of a heterocydic ring n number of atoms of the ring system f termination of the ring system... 

Nevertheless, there are situations where one wants to work with six four-membered rings in cubane (e.g., when considering the symmetry of the ring system). In this situation, one adds a sixth four-membered ring to obtain firom the SSSR the so-called extended set of smallest rings (ESSR). 

This reaction applies to many i,2 diketones, and is termed the Benzilic Acid Rearrangement. It provides a ready method for the preparation of disubstituted a4iydroxy-carboxylic acids. When applied to a cyclic 1,2-diketone, the ring system is necessarily reduced by one carbon atom for example, cyclohexan-i,2 ... 

Intramolecular 1,4-addition is useful for macrolide synthesis. An unusual molecule of punctaporonin B (272) has been synthesized by this 1,4-addition of 271(160]. Cyclization to form the seventeen-membered ring macrolide 273 was carried out at 0.1-0.5 vi concentration[161. The choice of ligands seems to be important in the macrocyclization. The 26-membered ring model 274 for a synthesis of the ring system of tetrin A was obtained in 92% yield by using triisopropyl phosphite as a ligand[162]. 

When the aldehyde group is directly attached to a carbon atom of a ring system, the suffix -carbaldehyde is added to the name of the ring system, e.g., 2-naphthalenecarbaldehyde. When the aldehyde group is separated from the ring by a chain of carbon atoms, the compound is named (1) as a derivative of the acyclic system or (2) by conjunctive nomenclature, for example, (1) (2-naphthyl)propionaldehyde or (2) 2-naphthalenepropionaldehyde. 

Sulfonium Compounds. Sulfonium compounds of the type R R R S X are named by citing in alphabetical order the radical names followed by -sulfonium and the name of the anion. For heterocyclic compounds, -ium is added to the name of the ring system. Replacement of > CH by sulfonium sulfur is denoted by the prefix thionia-, and the name of the anion is added at the end. 

Oxidation can also occur at the central metal atom of the phthalocyanine system (2). Mn phthalocyanine, for example, can be produced ia these different oxidation states, depending on the solvent (2,31,32). The carbon atom of the ring system and the central metal atom can be reduced (33), some reversibly, eg, ia vattiag (34—41). Phthalocyanine compounds exhibit favorable catalytic properties which makes them interesting for appHcations ia dehydrogenation, oxidation, electrocatalysis, gas-phase reactions, and fuel cells (qv) (1,2,42—49). 

Miscellaneous Reactions. The A/-hydrogen atom of diphenylamine is reactive and readily replaced by deuterium by treating with C2H OD. The addition of acid cataly2es the exchange of the hydrogen atoms on the ring system (11). 

Pyrrole has a planar, pentagonal (C2 ) stmcture and is aromatic in that it has a sextet of electrons. It is isoelectronic with the cyclopentadienyl anion. The TT-electrons are delocalized throughout the ring system, thus pyrrole is best characterized as a resonance hybrid, with contributing stmctures (1 5). These stmctures explain its lack of basicity (which is less than that of pyridine), its unexpectedly high acidity, and its pronounced aromatic character. The resonance energy which has been estimated at about 100 kj/mol (23.9 kcal/mol) is intermediate between that of furan and thiophene, or about two-thirds that of benzene (5). 

Despite considerable localization of tt-electrons at the nitrogen atoms of pyrimidine, the ring system is still sufficiently aromatic to possess substantial stability. This is a great advantage in the primary synthesis of pyrimidines, in the synthesis of pyrimidines from the breakdown or modification of other heterocyclic systems and in the myriad of metatheses required to synthesize specifically substituted pyrimidines. 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

The synthesis of these five-membered ring systems has classically been discussed in terms of the ring system formed. In recent years many synthetic procedures have been classified in terms of the bonds being formed and the position and nature of the heteroatoms involved. Both methods have their advantages, and also their drawbacks. 

Fused ring systems containing a pyrazole unit can be prepared either from the heterocyclic moiety by formation of a pyrazole ring or from the reaction between a pyrazole derivative and a suitably functionalized reagent. The ring systems thus obtained are discussed in detail in other chapters (Chapters 4.05, 4.35, 4.36) but it is of interest to discuss here those methods which start from a pyrazole derivative as the reactions involved can be considered as examples of the reactivity of pyrazoles. The most widely studied fused ring systems are the [5.6] systems and the examples described in this section will be chosen from this group and, occasionally, from [5.5] and [5.7] systems. 

Relatively few -unsubstituted isoxazolin-3-ones are known and a brief review was published by Quilico in 1962 the ring system was obtained by the hydrolysis of 3-methoxy-5-phenylisoxazole in 1961 62HC(17)l,p. 3). 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

The tributyitin hydride reduction of dihaloaziridines, e.g. (266), represents another example where the ring system has been maintained (79CJC1958). Especially noteworthy is the retained configuration associated with the reaction. This behavior differs from the cyciopropyl analog and was explained on the basis of increased s-character in the exocyciic bond caused by the nitrogen atom. 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

Cyclocondensation reactions with perfluoroalkyl-subsbtuted CO and CN multiple bond systems can be divided into several subgroups, according to the charge pattern of both reactants On the basis of this simple concept, hetero-l,3-dienes should undergo two types of condensation reactions, classified by the number of skeleton atoms of the diene being incorporated into the ring system (equation 10). 

Photolysis of 2,3,5,6-tetrakis(trifluoromethyl)-l,4-di hoshabenzene gives 1,3,4,6 tetrakis(tnfluoromethyl)-2,5-diphosphatncyclo[3 1 0 0 ]hex-3-ene, an ana logue of benzvalene containing phosphorus atoms in the ring system [267, 16S] (equation 40)... 

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