5‐Oxazolones, II. 2,4‐Diaryl‐4‐(2,4‐dinitroaryl)‐5(4H)‐oxazolones: Synthesis and Acid‐Catalyzed Transformation into 1‐Hydroxy‐1H‐indazole Derivatives

Abstract

f l -D i~~~~~d i N~o~~~5 ( 4 H ) -o x a z o l o n e s2 were prepared by arylation of the corresponding 5(4H)-oxazolones 1 under phase-transfer conditions with the corresponding l-halo-2,4-dinitrobenzenes.2,4-Diaryl-4-(3,5-dinitro-2-pyridyl)-5(4H)-oxa-. zolones 5 were obtained similarly from the corresponding 1 and 2-chloro-3,5-dinitropyridine. On reaction with methanol and ptoluenesulfonic acid, oxazolones 2 rearranged to the corresponding 1-hydroxy-1 If-indazole derivatives 8. Under the same conditions oxazolones 5 afforded a mixture of the correspondingly substituted 1 H-pyrazolo[4,3-b]pyridines 7 and substituted imidazo[1,5-a]pyridines 12. In all cases the solvolysis reaction, yielding substituted glycine esters 9 and 11, was competitive with the rearrangement. Reaction paths are discussed.Recently we described an alkylation method of 2,4-disubstituted 5(4H)-oxazolones under phase-transfer conditions '). An example of arylation was also reported. In the course of our research program on the use of 5-oxazolones in the synthesis of heterocyclic compounds, we extended the above procedure to a series of 4-(2-nitroaryl)-substituted 5(4H)-oxazolones aiming to explore their reactivity. We now report that these thermally stable oxazolones can be rearranged to indazoles under acidic catalysis. Synthesis of OxazolonesThe reaction of compounds 1 a, b, d -f with l-fluoro-2,4-dinitrobenzene in dichloromethane solution with an aqueous solution of sodium carbonate containing tetrabutylammonium bromide as phase-transfer catalyst at room temperature resulted in the formation of substituted 5(4H)-oxazolones 2a, b, f, g, h. Products 2a, b, f, h were easily purified by column chromatography, but 2g partially rearranged when contacted with silica gel yielding 8f as discussed later. Under analogous phase-transfer conditions 1 a and 2,4,6-trinitrochlorobenzene yielded oxazolone 2c. From 1 b and 2-nitrobenzyl chloride product 3 was similarly obtained. When oxazolone 1 c was treated with l-fluoro-2,4-dinitrobenzene under phase-transfer catalysis a mixture of 2e and the isomeric 5(2H)-oxazolone derivative 4 was formed. This outcome exactly parallels the results obtained in homogeneous phase in the presence of triethylamine2). As further example of arylating reagent, 2-chloro-3,5-dinitropyridine afforded 5 a and 5b from l a and I f under PTC conditions. They behaved similarly to 2g, showing a very high rearran- gement rate in the presence of silica gel which prevented the purification by chromatography. 5a could be purified by crystallization and fully characterized. 5 b was identified by its IR data and studied without further purification. 1 a and methyl 2-chloro-3,5-dinitrobenzoate afforded 2d and a byproduct which was recognized as deriving from 1 a and two mol of the aromatic chloride with C 0 2 elimination (M = 643). This compound was not studied further.The oxazolones were identified on the basis of their analytical and/or spectroscopical data, mainly from the characteristic IR absorption in the ranges of 1800-1820 cm-' (C=O). Th...

Polyfluoroarylation of oxazolones: access to non-natural fluorinated amino acids

“…6 The only example of S N Ar-type reactions with oxazolones is the addition to 2-nitroarenes, which undergoes subsequent cyclization with the nitro functional group to give indazole products (eqn 3) . 7 Though the reaction leads to a different product, it suggests that oxazolone enolate might be a competent nucleophile in the addition to perfluoroarenes.…”

Arylation of Azlactones using Diaryliodonium Bromides and Silver Carbonate: Facile Access to α‐Tetrasubstituted Amino Acid Derivatives

“…One was developed by Hartwig and co‐workers via Pd‐catalyzed reaction with aryl bromides in the presence of a bulky phosphine ligand at 80 °C or 100 °C 7a. The other one by Gelmi utilized the S N Ar reaction between 1‐halo‐2,4‐dinitrobenzenes/2‐chloro‐3,5‐dinitropyridine and azlactones 7b. We disclose herein a novel system for this with the usually less reactive diaryliodonium bromides as the aryl source, enabling the facile arylation of azlactones under very mild conditions to provide a wide range of α‐tetrasubstituted amino acid derivatives.…”

Precious-Metal-Free Heteroarylation of Azlactones: Direct Synthesis of α-Pyridyl, α-Substituted Amino Acid Derivatives

“…The arylation of stabilized enolates derived from amino acid aldimines is limited to S N Ar substitution of fluoro­nitroarenes and (fluoroarene)­chromium(0) carbonyl complexes, or to direct coupling with arylbismuth reagents . By contrast, the use of azlactones as relatively acidic amino acid enolate equivalents has been exploited in a broader range of arylation reactions (Scheme , panel A), including palladium-catalyzed cross-coupling to aryl halides, direct condensation with diaryliodonium salts, and S N Ar reactions with nitrohaloarenes, as well as direct Michael addition/aromatization reactions with quinones . Among all of these examples, there are only isolated reports of the synthesis of α-pyridyl,α-substituted amino acids. ,, …”

“…By contrast, the use of azlactones as relatively acidic amino acid enolate equivalents has been exploited in a broader range of arylation reactions (Scheme , panel A), including palladium-catalyzed cross-coupling to aryl halides, direct condensation with diaryliodonium salts, and S N Ar reactions with nitrohaloarenes, as well as direct Michael addition/aromatization reactions with quinones . Among all of these examples, there are only isolated reports of the synthesis of α-pyridyl,α-substituted amino acids. ,, …”

“…15 Among all of these examples, there are only isolated reports of the synthesis of α-pyridyl,αsubstituted amino acids. 8c,12b, 14 Londregan and colleagues at Pfizer have recently demonstrated the in situ activation/substitution of pyridine N-oxides using PyBroP with a range of nucleophiles, 16−18 including carbon-based nucleophiles such as β-dicarbonyls (malonates, ketoesters, diketones, and cyanoacetate) 17 and silyl ketene acetals. 18 Given the similar pK a of azlactones (ca.…”