Mesoionic fused systems

An alternative approach to 5-5 bicyclic fused ring systems utilizing a condensation reaction was described by Moderhack et al. <2000JPC591> (Scheme 10). The amino-substituted tetrazole derivatives 52 and 54 gave the neutral 53 as well as the mesoionic derivatives 55 in moderate to excellent yields (16-86% R = CH3 or Ph). 

Conversion of (l-methylimidazol-2-yl)thioglycolic acid (54) into the ring-fused mesoionic system (55) requires acetic anhydride (79JOC3803) and is accompanied by an acylation characteristic of reactive... 

Electrophilic substitution at nitrogen can occur in either ring depending on the nature of the substituents present. Electrophilic substitution at carbon proceeds readily in the presence of electron-releasing substituents. A wide variety of electrophiles have been studied. Mesoionic systems are readily substituted and cationic structures may become very reactive when conditions are chosen so as to promote intermediate formation of a pseudo-or anhydro-base. Sulfoxides are formed in the peracid oxidation of fused dihydrothiazoles. 

Mesoionic systems may be readily substituted by electrophiles. Thus the thiazolo mesoion (342) will couple with diazonium salts despite their relatively weak electrophilicity (80KGS621). Substitution in a fused heteroaromatic betaine azine ring, e.g. (343), also takes place with ease. The resonance form (344) of the mesoion (343) shows that the electrophile will attack at C-6. The substitution in this position is also predicted by MO calculations (73JHC487). Similarly the pyridine ring in pyridinium olates is active towards electrophiles and is substituted in the positions ortho and para to the olate function. Bromination of the 5-methyl derivative (321 R = Me) occurs exclusively in the 7-position which is rationalized via the intermediate (345). In the absence of a 5-substituent, attack in either the 5- or 7-position occurs the dibromide is readily formed. No bromination in the thiazole ring is observed. The 2-bromo derivative (346) has been made, however, by condensation between the appropriate mercaptopyridine and 1,1,2,2-tetrabromoethane. 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

The (l-methylimidazol-2-yl)thioglycolic acid 52 can be converted into the ring-fused mesoionic system 53 by reaction with acetic anhydride (Scheme 33) <1979JOC3803>. The thioether 54 with ethanolic sodium ethoxide gives the 3-benzylthiazolo[3,2- ]benzimidazole 55 (Scheme 34). 

Ring-fused mesoionic anhydro triazolium hydroxide systems 131 (84M11) that incorporate the thiocarbonyl ylide dipole undergo cycloaddition with both olefinic and acetylenic dipolarophiles the unstable 1 1 cycloadducts 132 and 133 yield ring-fused a-pyridinones 134 by elimination of hydrogen sulfide or sulfur, respectively (Scheme 42) (79JOC3803). 

Oxadiazoles," 1,3,4-oxadiazoles" and 1,2,5-oxadiazoles are well known, but the 1,2,3-oxadiazole system, which calculations indicate to be unstable relative to its ring-open diazo-ketone tautomer," is known only as a benzo-fused derivative (in solution) and in mesoionic substances, known as sydnones ," which have been well investigated. Furoxans ," which are formed by the dimerisation of nitrile oxides, have also been extensively studied. 1,2,3-Thiadiazoles, 1,2,4-thiadiazoles, 1,3,4-thiadiazoles" and... 

Cycloaddition Reactions.— Acetylenes undergo many types of cycloaddition reaction and provide valuable starting materials for the synthesis of carbo-and hetero-cyclic systems. Many acetylenes are dipolarophiles, and dimethyl acetylenedicarboxylate (DMAD), because of its ready availability, often plays this role in the formation of a variety of heterocycles. Mesoionic systems often function as the 1,3-dipoles, as in the formation of pyrrole (99) from the A -oxazolium-5-olates (munchnones) (100) and DMAD. The procedure can be extended to fuse pyrrole rings on to the piperidine rings of (101) and (102) in moderate yields. Further examples of... 

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