Mesoionic compounds, structures

Mesoionic compounds are heterocyclic compounds that cannot be represented by any uncharged formula but only as a hybrid of dipolar structures (1. 2). 

Mesoionic Compounds.These compounds cannot be satisfactorily represented by Lewis structures not involving charge separation. Most of them... 

The mesoionic compounds are represented by structures that cannot be properly described by Lewis forms not involving charge separation. Typical examples are the sydnones 80 the first example was obtained at the University of Sydney by the action of acetic anhydride on N-nitrosophenylglycine [75]. They were consequently named after the Australian town [76]. These structures are best approximated as resonance hybrids. They can be represented by any contributing mesomeric structure a, b, c or by the general structure d. 

A mesoionic compound PR-G-138-C1 (XXXIX) from Pharma Research in Canada is reported to lower blood pressure in man at low doses by a vasodilator type mechanism (43). This structure is related to SIN-10 (XL) which was reported earlier by Japanese scientists as active in dogs (44). Compounds related to structure XXXIX were compared in spontaneous hypertensive rats and those with the oxadiazole ring hydrogen replaced by chlorine or bromine were as active as the parent compound, although replacement by methyl caused a loss of activity (45). 

The mesoionic compounds can be named in several ways. The systematic name for structure (4) is a 3-substituted anhydro-5-hydroxy-l,2,3,4-oxatriazolium hydroxide. Similarly, structure (5) is named a 3-substituted anhydro-5-thiolo-l,2,3,4-oxatriazolium hydroxide, and structure (6) a 3-substituted anhydro-5-amino-l,2,3,4-oxatriazolium hydroxide. Frequently used names for structure (4) are 3-substituted 5-hydroxy-1,2,3,4-oxatriazolium hydroxide inner salt Chemical Abstracts), 3-substituted l,2,3,4-oxatriazol-5-ylio oxide, or 3-substituted l,2,3,4-oxathiazolylium-5-olate. For practical purposes, the term mesoionic l,2,3,4-oxatriazol-5-one is often used. Analogously, (5) and (6) are named mesoionic l,2,3,4-oxatriazol-5-thione and mesoionic l,2,3,4-oxatriazol-5-imine, respectively. 

Mesoionic compounds have been known for many years and have been extensively utilized as substrates in 1,3-dipolar cycloadditions.158-160 Of the known mesoionic heterocycles, munchnones and sydnones have generated the most interest in recent years. These heterocyclic dipoles contain a mesoionic aromatic system i.e. 206) which can only be depicted with polar resonance structures.158 Although sydnones were extensively investigated after their initial discoveiy in 1935,160 their 1,3-dipolar character was not recognized until the azomethine imine system was spotted in the middle structure of (206). C-Methyl-N-phenylsydnone (206) combines with ethyl phenylpropiolate to give the tetrasub-... 

Mesoionic compounds - These are defined as five-membered heterocycles that cannot be represented satisfactorily by any one covalent or polar structure and possess a sextet of electrons in association with the five atoms comprising the ring <1976AHC(19)1>. Two types of mesoionic compounds have been recognized and these are described as Type A and Type B. Mesoionic heterocycles are a subclass of heterocyclic mesomeric betaines <1985T2239>. For examples see Sections 2.41.2, 2.4.14, and 2.4.54. 

Substitution at position 4 of the pyrazolium ring also gives mesomeric betaines, illustrated by the pyrazolium-4-olates 32. The structure and chemistry of these mesomeric betaines with general structure 34 are different to those of the type A compounds, and are referred to as type B mesoionic compounds. They often react via an acyclic valence tautomer (see Section 2.4.5). 

The best known mesoionic compounds have five-membered rings, and initially it was advocated by Baker, Ollis, Ramsden and other authors that only five-membered heterocycles which cannot be satisfactorily represented by any one covalent or ionic structure possessing a sextet of TT-electrons in association with the five atoms comprising the ring may be called "mesoionic". Here, following Katritzky, mesoionic means a mesomeric betaine. The first such compounds to be discovered were sydnones, followed by miinchnones and then by diazolones. In all these compounds the Z-type atom is part of a carbonyl group, and two Y-type atom chains separate two odd-numbered chains of X- and Z-atom chains. Only the main resonance structures are displayed in formulas (Figure 11). 

The first syntheses of mesoionic compounds included 1,2,4-triazoles and their oxa and thia analogues. The structure postulated at first as (20) was rejected on stereochemical grounds and on consideration of the large dipole moment, to be replaced by a charged monocyclic structure, defined as mesoionic and considerably extended to a great variety of theoretically and practically important examples (57QR15, 76ahc(19)3). 

Measured dipole moments for a series of substituted tetrazoles gave interesting comparisons (56JA4197). The moments for 1-ethyltetrazole (5.46 D) and 2-ethyl tetrazole (2.65 D) were at either side of the mesoionic compound (7) (4.02 D) and the dipole moments could not be used to identify mesoionic structures. The dipole moments for the 1,5-disubstituted tetrazole structure were consistently high, >5.3 D, while those of the 2,5-disubstituted structure were low, <2.65 D theoretical calculations support this (61T237). Recently, dipole moment measurements were made on 5-(p-tolyl)tetrazole in dioxane (fio 4.99), its 1-methyl isomer 6.03) and its 2-methyl isomer (jUd 2.41) (80JHC1374). These results, when applied to the annular tautomerism of 5-( p-tolyl)tetrazole, suggested 60 10% of the 1-NH form in this medium. 

Dimethyl-3-phenyl-4-oxothieno[2,3-d]pyrimidine-2-thione (319) reacts with ethyl a-chlorophenylacetate in the presence of anhydrous potassium carbonate in boiling dimethylformamide (DMF)-acteone for 12 hr to give 6,7-dimethyl-2,9-diphenyl-9a-ethoxy-9-oxothiazolo[3,2-fl]thieno [2,3-d]pyrimidin-3(2//)-one (321) in 90% yield [81IJC(B)538] (Scheme 75). The absorption at 1745 cm (five-membered lactam C=0) in addition to that at 1690 cm (six-membered C=0) in the product supports the cyclic structure 321. The formation of 321 must have been through the initially formed unstable mesoionic compound 320, which adds 1 mol of ethanol, liberated during reaction, to afford 321. 

Facile reaction of electron-deficient olefins (dipolarophiles) such as rra/i5-dibenzoylethylene, dimethyl fumarate, furanonitrile, methyl vinyl ketone, ethyl crotonate, ethyl acrylate, ethyl methacrylate, and dimethyl maleate with a mesoionic compound containing a masked thiocarbonyl ylide skeleton gives stable 1 1 cycloadducts. The structure of the cycloadduct was established by its carbonyl absorption in IR spectra and the molecular ion peak [M]. The stereochemistry of the cycloadducts was, however, secured by NMR spectra (74JOC3631) (Scheme 100). 

The mesoionic compounds 2 (also named l,3-dithiolylium-4-olates or l,3-dithiolium-4-olates) and 3 (also named 1,3-dithiolylium-4-thiolates or 1,3-dithiolium-4-thiolates) are described by canonical structures 2,3a-e, of which those with an oxyanion or a thioxyanion 2a and 2b, are presumably most representative. 

Mesoionic Compounds. These compounds cannot be satisfactorily represented by Lewis structures not involving charge separation. Most of them contain five-membered rings. The most common are the sydnones, stable aromatic compounds that undergo aromatic substitution when R is hydrogen. 

Compounds originally thought to have the stereochemically strained structure (20) are now understood to be mesoionic compounds <57Qr15) (see Section 4.12.2.5). 

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