Azomethine imines sydnones

It is possible to compare the reactivity of some 1,3-dipoles inserted in cyclic structures with that of the same dipoles in open chains. This comparison, recalling that between cyclic and open-chain dienes (Section 4.1.3), is limited to two classes of 1,3-dipoles without a double bond , namely azomethine imines and oxides. For the former, there are data in Table 12 for the reaction with dimethyl acetylene dicarboxylate (iii) the cyclic azomethine imine (sydnone) is about 300 times less reactive than the open-chain cyanoazo-methine imine. In the case of nitrones, a typical comparison is. for reaction with ethyl crotonate in toluene at 100°C "... 

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. 

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-... 

The mesoionic compounds known as sydnones serve as cyclic azomethine imines. Thus, sydnone (167), isolable after preparation from die corresponding nitrosamine, underwent cyclization as an azomethine imine at 20-35 C (Scheme 52).86 Photolysis of sydnones also results in cyclization but through nitrile imine intermediates vide infra). 

The products derived from intermolecular cycloaddition of sydnones readily lose carbon dioxide. If the original cycloaddition is carried out on a diene, the resulting azomethine imine intermediate can be trapped intramolecularly. Thus, 1,5-cyclooctadiene cycloadded to a sydnone to afford the cycloadduct (168).78b It is theorized that the intermolecular monocycloadduct (169) was formed, lost carbon dioxide, and cycloadded as a cyclic azomethine imine to the remaining C—C double bond. Conjugated dienes have been shown to undergo a similar sequence.87... 

Sydnones can be regarded as cyclic azomethine imines and as such they undergo thermal cycloaddition reactions with a range of dipolarophiles. Thus, reaction with phenyl isocyanate converts 401 into 1,2,4-triazole 402. On photolysis, 3,4-diarylsydnones lose carbon dioxide and give nitrile imines, which can also be intercepted by dipolarophiles. Thermal reactions with acetylenic dipolarophiles lead to the formation of pyrazoles (Scheme 88) however, these reactions are rarely completely regioselective with unsymmetrical alkynes, e.g., <2000BKC761, 2000TL1687>. 

The class of azomethine imines includes the sydnones, see Sect. 6.3. 

The answer to this dilemma was provided by Huisgen et al. (1962 a, 1962 b) by the cycloaddition reaction of C-methyl-A-phenylsydnone (6.10) with styrene, which yields, via the bicyclic intermediate 6.11 and elimination of CO2, 4,5-dihydro-5-methyl-l,3-diphenyl-li/-pyrazole (6.12). As mentioned briefly in Section 6.2 (Table 6-1, footnote a), sydnones are cyclic azomethine imines. As Huisgen (1968) demonstrated later, sydnone and azomethine imine cycloadditions are kinetically very similar with respect to solvent effects and in the sequence of reactivity with a series of 11 dipolarophiles. 

Cycloadditions were found to be first-order reactions with respect to both 1,3-dipole and dipolarophile, in all cases so far investigated. There are some limits to kinetic studies of these reactions, as many 1,3-dipoles are very reactive substances. While aryl azides, diazoalkanes, some classes of azomethine imines (for instance sydnones), and some classes of azomethine oxides (nitrones) are stable and isolable, azomethine ylides are usually unstable, an exception being represented by a mesoionic oxazolone that has been used for kinetic investigations benzonitrile oxide has a very limited stability, although some substituted derivatives are stable for long periods nitrile imines are not commonly isolable because of their strong tendency to dimerise. 1,3-Dipoles of... 

Phenyl azide appears as a rather unreactive 1,3-dipole. Of the azomethine imines that follow, sydnone is more stable than the open cyano-derivative. Diazomethane is a very reactive compound, but double phenyl substitution reduces its reactivity. The highest rate coefficients are those of reactions of the mesoionic oxazolone. Reactivity varies by five or six orders of magnitude from azide to mesoionic oxazolone. 

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