Mesoionic systems

There are a substantial number of heterocyclic substances for which no plausible, unpolarised mesomeric structure can be written such systems are termed mesoionic . Despite the presence of a nominal positive and negative charge in all resonance contributors to such compounds, they are not salt-like, are of course overall neutral, and behave like organic substances, dissolving in the usual solvents. Examples of mesoionic 

Structure of a sydnone resonance contributors (mesomeric structures) 

Mesoionic structures occur amongst six-membered systems too - one example is illustrated below. 

If there is any one feature that characterises mesoionic compounds it is that their dipolar structures lead to reactions in which they serve as 1,3-dipoles in cycloadditions. 

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As apparent from the contributing resonance structures, both mesoionic systems contain an azomethinylide contribution, accounting for the reaction with representative dipolarenophiles to give cycioadducts such as 3 or 4 (Scheme 4). The cydoadditions and extrmsion reactions of the adducts have been the mam object of investigation. since previous reviews on me.soionic thiazoles (2.9V Results appearing since 1969 and before June 1976 are reported for each type of compound in this chapter. Tables VIIRl-5 contain all mesoionic thiazoles described before June 1976. 

Substitution of the nitrogen atom in (289) and subsequent ring closure of (293) under acid cyclodehydration conditions gave the mesoionic system anhydro-5-hydroxythiazoIium hydroxide (294). These reactions are analogous to the cyclodehydration of the A-nitrosogly-cines (295) with acetic anhydride to give the sydnones (296) (see Chapter 4.21). 

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

Although in its reactions with several mesoionic systems diphenylthiirene dioxide (439) does not lose SO2 from the cycloadducts, in its reactions with pyridinium, quinolinium and isoquinolinium phenacylides it behaves as an acetylene equivalent. Thus, reaction of (439)... 

H(15)1349] (Scheme 54). A number of mesoionic systems related to 148 have been chlorinated and brominated (73JHC487). 

The numbering of the 1,3,4-thiadiazole ring is given below. The present chapter is intended to update the previous work on the aromatic 1,3,4-thiadiazole 1, the nonaromatic A2-thiadiazolines 2, A3-thiadiazolines 3, the thiadiazoli-dines 4, the tautomeric forms 5 and 6, and the mesoionic systems 7. Reference is made to earlier chapters of CHEC(1984) and CHEC-II(1996) where appropriate. 

Baker,67 Ollis,68 Ramsden,69 and other authors70 defined mesoionic systems as five-membered rings that cannot be represented by normal covalent structures. Following Katritzky,71 they are now universally named systematically as mesomeric betaines. 

A classification according to the six structures in Scheme 3 is meaningless for compounds that are themselves anions (since the negative charges on the anions shown in Scheme 3 are arbitrarily located) and not very useful for neutral systems. A subdivision into anions (e.g., 16), neutral molecules (e.g., 19 and 20), mesoionic systems (e.g., 15 and 17), and cations (e.g., 2740 and 2841), though important when considering reactivity, is also inadequate. 

Two closely related mesoionic systems, 59 and 60, were obtained by reductive cyclization of 61 with TEP,62 and by oxidation of 62 with lead tetraacetate,63 respectively. The pyrazolo[4,3-c]pyrazole 64 was obtained from the azo compound 63 by reduction with dithionite, followed by diazotization of the resultant amine and cyclization with... 

Of the mesoionic systems, (40) and its aza derivatives (43), (44) and (49) have been designated as Class B by Ollis (76AHC(l9)l), including compounds with X = CRR there are 88 total systems. Class A mesoionic compounds include (41), (42) and their aza derivatives (45)-(48), (50) and (51), giving a total of 144 systems. Members of the latter group contain 1,3-dipoles, often reflected in their pronounced ability to undergo cycloaddition reactions. 

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... 

For the first time, derivatives of the new tellurium-containing mesoionic system, 1,2-oxatellurolyl-l-ium halides 21, were prepared by Detty via cyclization of j8-aryltelluropropenoyl chlorides 22, which in turn were synthesized starting from diaryl ditellurides as shown in the scheme. Under the action of Lewis acids (A1C13) or upon heating, compounds 22 rearrange to 21 in 50-96% yields (83JA875). 

Anhydro-5-hydroxyoxazolium hydroxides lacking substituents at C(4) dimerize spontaneously by a process in which one molecule acts as an electrophile and the other as a nucleophile (Scheme 21). This accounts for the fact that dimeric products of this type are obtained by the action of dicyclohexylcarbodiimide on acylamino acids of the general formula R1C0NR2CH2C02H. Substituents at position 4 stabilize the mesoionic system the first compounds to be prepared were the acetyl derivatives (220) (B-49MI41800) and (221) (58Cl(L)46l) and much of the more recent work has been carried out with the relatively stable methyldiphenyl compound (222). This miinchnone decomposes above 115 °C to yield the allene (225) with loss of carbon dioxide. The mechanism proposed for this remarkable reaction (Scheme 22) involves valence isomerization to the ketene (223), which undergoes a 1,3-dipolar cycloaddition with the miinchnone. The product loses carbon dioxide to form a new betaine (224), which collapses to the allene as shown. 

Carbonyl compounds and other dipolarophiles containing heteroatoms react with miinch-nones. Thus benzaldehyde forms the betaine (245) which suffers ring-cleavage to yield the enamine (246 equation 65). Thiocarbonyl compounds and nitrosobenzene behave in an analogous manner. The action of dipolarophiles containing cumulative double bonds results in the formation of new mesoionic systems. Thus carbon disulfide and phenyl isothiocyanate afford a zwitterionic thiazole and imidazole, respectively (Scheme 25). 

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). 

Boat conformation of the triazocine ring was observed in tricyclic mesoionic tetrazolium derivative of 1,3,5-triazocine 9. Bond lengths in the tetrazolium ring were in good correspondence with those of the similar 1,3-diphenyltetrazolium mesoionic systems <2000JHC1129>. 

With many treatises about heterocyclic compounds, and with the impressive series Comprehensive Heterocyclic Chemistry in three series (84CHEC1,96CHEC2-1,08CHEC3-1), it makes little sense to deal in detail with individual compounds. Rather, this review will discuss trends observed when m increases stepwise from m = 4 to m = 9. Actually, it will be seen that there are no heterocyclic sextet-aromatic systems with eight-or nine-membered rings, but we have included such structures because it may be worthwhile to explore whether their strain-free bicyclic isomers may evidence isomerization to planar monocyclic mesoionic systems. 

Of the mesoionic systems, (40) and its aza derivatives (43), (44) and (49) have been designated as Class B by Ollis <76AHC(19)1), including compounds with X = CRR there... 

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