Synthesis of oxazoles by the reaction of ketones with iron(III) solvates of nitriles.

Kotani, Eiichi; Kobayashi, Shigeki; ADACHI, M.; Tsujioka, T.; Nakamura, Kouji; Tobinaga, Seisho

doi:10.1248/cpb.37.606

Cited by 24 publications

(24 citation statements)

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“…The combined organic layers were dried over anhydrous Na 2 SO 4 , filtered, and concentrated. The crude residue was submitted to gravity-column chromatography on silica gel (hexane/ ethyl acetate, 9:1) to afford 3 as white crystals (0.92 g, 84%); mp 94− 96 °C; R f = 0.26 (hexane/ethyl acetate, 5:1); FT-IR (neat film): 3067, 2972, 1558, 1318, 1148 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d,J = 8.4 Hz,2H),1H),6H),6H), 4.66 (s, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ) δ 151. 5, 147.6, 138.2, 136.2, 134.3, 131.6, 129.3, 129.1, 128.7, 128.65, 128.60, 128.4, 128.1, 127.9, 126.6, 55.9 General Procedure for the Preparation of Alkylated Sulfones (5−17).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Synthesis of Extended Oxazoles III: Reactions of 2-(Phenylsulfonyl)methyl-4,5-diaryloxazoles

Patil

Luzzio

2016

J. Org. Chem.

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2-((Phenylsulfonyl)methyl)-4,5-diphenyloxazole is a useful scaffold for synthetic elaboration at the 2-methylene position thereby affording extended oxazoles. The corresponding α-sulfonyl anion reacts smoothly with diverse alkyl halides giving monoalkylated (47-90%), dialkylated (50-97%), and cyclic (59-93%) products. The reductive desulfonylation of the monoalkylated and selected dialkylated products was optimized with a magnesium/mercuric chloride reagent system and afforded desulfonylated products in the range of 66-97%. The anti-inflammatory Oxaprozin was prepared using the α-sulfonyl carbanion strategy along with optimized desulfonylation.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Synthesis of Extended Oxazoles III: Reactions of 2-(Phenylsulfonyl)methyl-4,5-diaryloxazoles

Patil

Luzzio

2016

J. Org. Chem.

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“…Although Lora-Tamayo and coworkers described the tin (IV) chloride-mediated Ritter reaction of a-halo ketones more than 40 years ago, 7 the need for stoichiometric quantities of tin-based reagents together with the rather limited availability of a-halo ketones appear to have discouraged the use of this method. 8 A related transformation is the reaction of nitriles with reactive unsubstituted a-oxo triflates generated in situ by oxidation of methyl ketones with reagents based on thallium(III), 8 mercury(II), 9 iodine(III), 10 iron(III), 11 or copper(II). 12 These methods provide moderate-to-good yields of 2,4-disubstituted oxazoles, and they are useful in situations where the requisite a-hydroxy or a-sulfonyloxy carbonyl compound is not readily available.…”

Section: Scheme 1 Unexpected Formation Of Oxazole 2a From Methyl Mandmentioning

confidence: 99%

Preparation of Substituted Oxazoles by Ritter Reactions of α-Oxo Tosylates

Lai¹,

Taylor²

2010

Synthesis

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The Lewis acid catalyzed Ritter reaction of a-oxo tosylates with nitriles forms the basis of an efficient synthesis of oxazoles. Oxazoles with various substituents can be readily prepared from inexpensive starting materials.The oxazole ring is widely found in medicinal agents, biologically active natural products, and organic materials. 1 Much effort has been devoted towards devising methods for the synthesis of substituted oxazoles. Although venerable protocols such as the Robinson-Gabriel dehydration of 2-acylamino ketones 2 and the Cornforth method 3 remain in widespread use, metal-catalyzed reactions are growing rapidly in popularity and frequency of application. 4 Here, we report a general protocol for the synthesis of oxazoles by means of the Ritter reaction of a-oxo carbocations. 5 This approach permits the construction of a range of trisubstituted oxazoles from two readily available classes of organic feedstocks: nitriles and a-hydroxy carbonyl compounds.In the course of developing carbon-carbon bond-forming reactions of a-carbonyl carbocations as 'reversed polarity' variants of the enolate alkylation reactivity pattern, 6 we explored the reaction of the methyl mandelate-derived tosylate 1a with allyl(trimethyl)silane catalyzed by scandium trifluoromethanesulfonate in acetonitrile (Scheme 1). The expected allylation product was not observed; instead, oxazole 2a was obtained, presumably through a Ritter reaction with the solvent, followed by ring closure of the resulting nitrilium ion and loss of a proton. Scheme 1 Unexpected formation of oxazole 2a from methyl mandelate-derived tosylate 1aWe were surprised to find, upon surveying the literature, that this mode of reactivity is underexploited as a method for the synthesis of oxazoles. Although Lora-Tamayo and coworkers described the tin (IV) chloride-mediated Ritter reaction of a-halo ketones more than 40 years ago, 7 the need for stoichiometric quantities of tin-based reagents together with the rather limited availability of a-halo ketones appear to have discouraged the use of this method. 8 A related transformation is the reaction of nitriles with reactive unsubstituted a-oxo triflates generated in situ by oxidation of methyl ketones with reagents based on thallium(III), 8 mercury(II), 9 iodine(III), 10 iron(III), 11 or copper(II). 12 These methods provide moderate-to-good yields of 2,4-disubstituted oxazoles, and they are useful in situations where the requisite a-hydroxy or a-sulfonyloxy carbonyl compound is not readily available. However, they are limited in terms of the range of nitriles that can be used, and they require the use of toxic and/or expensive oxidants. In an example that is particularly relevant to the work described here, trifluoromethanesulfonic anhydride was used to oxidize 1-(methylsulfanyl)acetone to the corresponding triflate, which underwent Ritter reaction via a sulfur-stabilized carbocation to generate the corresponding methylsulfanyl-substituted oxazoles. 13

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“…There are several methods for the preparation of oxazoles described in the literature. These include ring-closure reactions of diazocarbonyl compounds with amides or nitriles [ 16 ], α-haloketones and amides [ 17 – 19 ], cyanohydrins and aldehydes (Fischer synthesis) [ 20 – 21 ], or oxidative additions of α-methylene ketones to nitriles [ 22 – 23 ]. An alternative approach consists of the ring expansion of azirines, which can be prepared from vinyl azides 1 , by the reaction with carbonyl compounds.…”

Section: Introductionmentioning

confidence: 99%

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

Rossa¹,

Suveges²,

Sá³

et al. 2018

Beilstein J. Org. Chem.

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An efficient three-step protocol was developed to produce 2-(azidomethyl)oxazoles from vinyl azides in a continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their subsequent treatment with NaN3 in aqueous medium to give azido oxazoles in good selectivity. Process integration enabled the synthesis of this useful moiety in short overall residence times (7 to 9 min) and in good overall yields.

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Synthesis of oxazoles by the reaction of ketones with iron(III) solvates of nitriles.

Cited by 24 publications

References 0 publications

Synthesis of Extended Oxazoles III: Reactions of 2-(Phenylsulfonyl)methyl-4,5-diaryloxazoles

Synthesis of Extended Oxazoles III: Reactions of 2-(Phenylsulfonyl)methyl-4,5-diaryloxazoles

Preparation of Substituted Oxazoles by Ritter Reactions of α-Oxo Tosylates

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

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