Oxazolones mesoionic

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. 

Double cyclization of the phenylglycine o-carboxylic acids 611 (R = H) with acetic or benzoic anhydride by heating gave the mesoionic oxazolones 612 and 613, respectively, which upon treatment with BF3 Et20 gave 615... 

Reaction of the mesoionic oxazolone 620 with acetylenedicarboxylic ester 621 gave the cycloadduct 622 in aprotic solvents and the Michael adducts... 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

Similarly, 1,1-dioxides are formed either by the cyclodehydration of diacylsulfones and ammonia (Scheme 115) (720S(52)135) or through the action of sodamide on bis(2-chlorovinyl) sulfones (255) which are themselves obtained by a two-step sequence from alkynes (Scheme 116) (72S311). A less general route involves the addition of the thiirene sulfone (256) to the mesoionic oxazolone (257). In this example the initial adduct (258) eliminates carbon dioxide spontaneously, thus affording the 1,4-thiazine (259) (75CL1153). 

Huisgen and co-workers486,490 have described a useful synthesis of N-substituted pyrroles (41) from mesoionic oxazolones (39) via the intermediates 40, which were not isolated. A variety of acetylenic esters (phenylpropiolic, propiolic, tetrolic, and DMAD) were used. The kinetics of these reactions have been studied.491 The addition of carbon... 

Asaro, M. F. Nakayama, I. Wilson, R. B. Formation of sterically hindered primary vicinal diamines from vicinal and geminal dinitro compounds. /. Org. Chem. 1992, 57, 778-782. Rodriguez, H. Marquez, A. Chuaqui, C. A. Gomez, B. Oxidation of mesoionic oxazolones by oxygen. Tetrahedron 1991, 47, 5681-5688. Heras, M. Ventura, M. Linden, A. Villal-gordo, J. M. Reaction of a-iminomethylene amino esters with mono- and bidentate nucleophiles a straightforward route to 2-amino-lH-5-imidazolones. Tetrahedron 2001, 57, 4371—4388. 

The pyridinium perchlorate (212), which is the precursor of the mesoionic oxazolone (213), is formed by the action of acetic anhydride and perchloric acid on l,2-dihydro-2-oxopyridin-l-acetic acid. The mesoion (213) is chemically unstable and is generated in solution for its reactions by treatment with a tertiary amine. Compound (213) is easily substituted at C-3, and with trifluoroacetic anhydride forms the stable 3-trifluoroacetyl mesoion (70JCS(C)1485). 

Cycloaddition-extrusion-ring expansion reactions of five-membered mesoionic oxazolones and thiazolones with 2,3-diphenylcyclopropenethione produced pyridine-4(l//)-thiones... 

Oxazolones are simply cyclic anhydrides of A-acyl-a-amino acids, and are constructed in the way that this implies. If the nitrogen also carries an aUcyl group, cyclisation " can only lead to an overall neutral product by adopting a zwitterionic stracture, for which no neutral canonical form can be written - a mesoionic structure. Mesoionic oxazolones (named miinchnones by Huisgen after their discovery at the University of Munchen, Germany) undergo ready dipolar cycloadditions,with loss of carbon dioxide from the initial adduct the examples" show the conversion of a miinchnone into a mesoionic thiazolone and into an imidazole. 

Only 2,3-dihydropyrrolo[2,l-(>]thiazoles have been described. Reaction of 7V-acetylthiazolidine-2-carboxylic acid (303) in the presence of acetic anhydride provides mesoionic oxazolone intermediates (304) which undergo 1,3-dipolar cycloaddition with DMAD, to give unstable intermediate (305) which rapidly eliminates carbon dioxide to give 2,3-dihydro-5-methylpyrrolo[2,l-( ]thiazole-6,7-dicarboxylate (306) (Scheme 55) <88JMC1427>. 

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. 

Mesoionic oxazolones 154, prepared from 153, allowed the synthesis of 3-CF3-pyrroles. Thus, their reactions with fluorinated derivatives of ethyl propiolate 155 led to the alkyl pyrrole-3-carboxylates 156 [65]. Similarly, the reaction of compound 157 with hexafluorobut-2-yne gave the pyrrole 158 [66]. 

As it was mentioned previously, mesoionic oxazolones were used as dipolaro-philes in the synthesis of 2-CF3-pyrroles. A tandem addition of 1,2-binucleophiles to oxazolones also led to pyrroles, but bearing the CFs-group in 3-position. For instance, the reaction of the oxazolones 426 with aminomalonate 427 gave the pyrrolidine derivative 428, which formed 429 by reaction with acetic anhydride. Treatment of 429 with lithium hydroxide resulted in a decarboxylation giving the pyrrole 430 [140]. 

Six- and seven-membered nitrogen heterocycles may be made by a newly reported reaction of the mesoionic oxazolone (438) with cyclopropenes and cyclobutenes, respectively (Scheme 61). Similarly, compound (438) reacts... 

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