Mesoionic betaines

Tire and NMR parameters of some 1-alkyl-4-benzimidazolyl-2-idene- (type 72) and l-alkyl-4-(5-methylpyrazolyl-3-idene)-l,4-dihydro pyridines (type 73) were discussed in 89CC1086 and 91JOC4223. Comparison of the shifts for DMSO-dg and CDCI3 solutions with data reported for quaternary pyridinium compounds as well as anionic species in the azole series and data obtained for mesoionic betaines of the azinium azolate class left no doubt that these heterofulvalenes have a betaine character and, therefore, the NMR signals correspond to their dipolar resonance form. 

A single crystal structure analysis of 56a revealed the molecule as a symmetric mesoionic betaine having a plane of symmetry (6 2w) with all delocalized C-N bonds being approximately the same length (1.34 A). In this respect, the molecule can be considered as a cyanine chromophore <2004CC1860>. 

Each of the aromatic monocationic systems (14)-(27) can be converted into a neutral system by substitution of an anionic O, S or NR group on to a ring carbon atom. However, (14) and (15) each give three such systems, (16)-(21) two each, and (22)-(27) one each. The resulting 24 systems can be divided into two groups 12 systems for the azolinones and related compounds (Scheme 4) and 12 systems for the mesoionic (betaine) compounds (Scheme 5). 

Prompted by our earlier work dealing with the internal dipolar cycloaddition reaction of mesoionic oxazolium ylides of type 74, we subsequently studied the rhodium(II) catalyzed reactions of the related a-diazo ketoamide system 154 <97JOC2001 04OL3241 05JOC2206>. Attack of the amido oxygen at the rhodium carbenoid produces a push-pull carbonyl ylide dipole (i.e., 155) that is isomeric with the isomiinchnone class of mesoionic betaines. 

The various fonns of betaines are very important for their charge control functions in diverse applications and include alkylbetaines, amidoalkylbetaines and heterocyclic betaines such as imidazolium betaines. Some surfactants can only be represented as resonance fonns having fonnal charge separation, although the actual atoms bearing the fonnal charge are not ftmctionally ionizable. Such species are mesoionic and an example of a trizaolium thiolate is illustrated in table C2.3.3. 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

Most of the reported 1,2,5,6-tetrazocine systems probably do not exist in the monocyclic form but rather as the tetraazapentalene betaine structure (see Introduction) 2 3 7"13 for the tetra-phenyl-substituted system, the compound does actually exist as the mesoionic tetraphenyl-[1,2.3]triazolo[l,2-h][l,2,3]triazole, as determined by H and 13C NMR spectroscopy.15 The following syntheses arc therefore questionable. 

The chemistry of tetrazolium thiolates and other mesoionic tetra-zoliums has been extensively reviewed.297,298 Tho ugh there are no reports of the chemical reduction of thiolates to formazan-like structures, the polarographic reduction of the complex betaines (146) to formazans has been reported.655... 

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. 

Huckel s 4n+2 //-electron rule is a necessary but not a sufficient condition for aromaticity. Coplanarity and electronegativity restrictions of constituent atoms represent the most important restrictions. Phos-phole is a marginally aromatic five-membered heterocycle76 (see further examples and discussion). Mesoionic compounds, mesomeric betaines, and 2H-and 4i+-pyrone have all been considered to be weakly aromatic or non-aromatic, though their conjugated acids are aromatic. Spectroscopic data evidenced the aromaticity of dioxolium and oxathiolium cations 59 (Scheme 28) and mesoionic oxathioles not in the classical sense but by their ring currents and chemical stability.77... 

Potts, Ehrlinger, and Nichols573 treated the mesoionic 1,3-thiazine betaine (92) with DMAD and obtained the thiophene 94 (28% yield), which was also synthesized from 97 and DMAD. Some 96 (R = 4-MeOC6H4) was also formed through rearrangement of the starting material. Product 94 could arise from 93 by loss of phenyl isocyanate or from 95 by loss of carbon monoxide. Replacement of the p-methoxy-... 

Calculations of the structure of the mesoionic thiopyrylium-3-olate 74 suggest that the C-S bond lengths are similar to those in the pyrylium cation at ca. 168 pm, perhaps supporting the fully charge-separated betaine structure. However, the charge at oxygen is closer to 0.5 than the 1.0 expected for such a structure. Furthermore, the nucleus-independent chemical shift value is appreciably lower than that for the thiopyrylium cation. These data point toward an ylidic structure with an acceptor moiety rather than an aromatic cation and an exocyclic oxyanion <2002IJQ(90)1055>. 

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). 

Some reactions of munchnones occur via acylamino ketenes, the covalent valence tautomers of the betaines. The ketenes are intermediates in the thermolysis (see Scheme 22) and in the formation of azetidinones from imines (equation 69) they are thought to be involved in the aminolysis of the mesoionic compounds, which results in amides of a-acylamino acids, and in the formation of the benzodioxin (247) by the combined action of acetic anhydride and tetrachloro-o-benzoquinone on Af-benzoylalanine (equation 70). 

The standard method of preparing anhydro-5-hydroxyoxazolium hydroxides (300) is by dehydration of iV-substituted a-acylamino acids, usually with acetic anhydride (equation 154) dicyclohexylcarbodiimide and trifluoroacetic anhydride have also been used. N-Acylglycines (299 R3=H) give rise to unstable mesoionic oxazoles which tend to dimerize (see Section 4.18.3.1.5(0) if such acids are treated with trifluoroacetic anhydride, stable trifluoroacetyl derivatives (300 R3 = CF3CO) are isolated. Numerous unstable betaines (300 R1, R = alkyl or aryl, R -H) have been generated by the action of triethylamine on the corresponding hydroperchlorates, prepared by the method shown in equation (151). 

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