Trisubstituted Oxazoles Research Articles

2-Phenyl-4-bis(methylthio)methyleneoxazol-5-one: versatile template for diversity oriented synthesis of heterocycles

4-Bis(methylthio)methylene-2-phenyloxazol-5-one (1) has been shown to be a versatile template for the synthesis of novel heterocyclic scaffolds. The key protocol involves nucleophilic ring opening of 1 with various primary aliphatic, aromatic amines and diamines to give open-chain amide adducts which are transformed into 4-bis(methylthio)methylene-2-phenyl-1-alkyl/arylimidazol-5-(4H)-ones (5) in good yields in the presence of anhydrous NaOAc/AcOH. Similarly, the amide adducts 4h-i from 3,4-dimethoxyphenylethylamine and tryptamine undergo interesting rearrangement in the presence of POCl(3) to furnish 1-(2-phenyl-5-methylthio-4-thiazolyl)dihydroisoquinoline and β-carboline derivatives 8-9 in good yields. The amide adduct 14 from o-phenylenediamine on exposure to refluxing acetic acid or in the presence of Ag(2)CO(3) affords substituted 3H-1,5-benzodiazepinone, 2-(5-methylthio-2-phenyl-4-oxazolyl)-1H-benzimidazole and trisubstituted oxazole (15-17), whereas the bis-adduct from ethylenediamine yields ethylene bridge tethered bis-imidazole 23 and bis-oxazole 24 under similar reaction conditions. Probable mechanisms for the formation of various products have been suggested.

ChemInform Abstract: Preparation of Substituted Oxazoles by Ritter Reactions of α‐Oxo Tosylates.

AbstractLewis acid catalyzed Ritter reaction of α‐oxo tosylates, trifluoroacetates and alcohols with nitriles under optimized conditions affords trisubstituted oxazole products in good to excellent yields.

ChemInform Abstract: A Novel Double Addition of Isocyanoacetamide to N-Sulfonylimines for the Synthesis of Trisubstituted Oxazoles.

Abstract The reaction of isocyanoacetamide with N-sulfonylimine gives a novel double addition product in the absence of acid, base and catalyst to form 2,4-disubstituted-5-amino-1, 3-oxazole. A possible mechanism of this reaction is discussed.

ChemInform Abstract: Modular Synthesis of Tetrasubstituted Imidazoles and Trisubstituted Oxazoles by Aldimine Cross‐Coupling.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Modular Synthesis of Tetrasubstituted Imidazoles and Trisubstituted Oxazoles by Aldimine Cross‐Coupling

Modular Synthesis of Tetrasubstituted Imidazoles and Trisubstituted Oxazoles by Aldimine Cross‐Coupling

Novel p38 Inhibitors with Potent Oral Efficacy in Several Models of Rheumatoid Arthritis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel p38 inhibitors with potent oral efficacy in several models of rheumatoid arthritis

A library of trisubstituted oxazoles, thiazoles, imidazoles (1,2,4- and 2,4,5-substituted) and imidazo[1,2- b]pyridines was prepared and evaluated in vitro as p38α inhibitors and in vivo in several models of rheumatoid arthritis. Four structures–– 32, 37, 45 and 59––were identified as potent inhibitors of p38α with high efficacy in the LPS induced TNFα release model in the mouse, the adjuvant induced arthritis and the collagen induced arthritis in the rat with ED 50s between 1.0 and 9.5 mg/kg p.o.

ビスマスの創り出す有機化学 合成と応用

The syntheses and reactions of bismuthonium salts and bismuth ylides are reported. Various types of bismuthonium salts bearing a Bi-Csp3, Bi-Csp2, or Bi-Csp bond have been prepared by the Lewis-acid promoted reaction of triphenylbismuth difluoride with organometallic reagents. The bismuthonium salts thus obtained behave as alkyl cation equivalents, alkenyl cation equivalents, and carbene precursors. The bismuth ylides bearing a carbonyl group at the ylidic carbon react with carbonyl compounds to undergo epoxidation, transposition, or ring expansion depending on the structure of the substrates employed. These reaction modes are characteristic of bismuth among the group 15 elements. The stabilized bismuth ylides bearing a highly cross-conjugated ylidic carbon decompose, at an elevated temperature or in the presence of a copper catalyst, to give trisubstituted oxazoles. The observed unique reactivities of the bismuthonium salts and the bismuth ylides are ascribed to the good leaving ability of the triarylbismuthonio group.

Synthesis and Reactivity of 4-Silylated Oxazoles

Treatment of (triethylsilyl)diazoacetates with rhodium (II) octanoate and a range of substituted nitriles generates trisubstituted oxazoles bearing a triethylsilyl group in the 4-position. Fluoride-mediated desilylation yields 3,5-disubstituted oxazoles, whereas treatment with N-halosuccimides allows the introduction of halogens at the 4-position.

A novel double addition of isocyanoacetamide to N-sulfonylimines for the synthesis of trisubstituted oxazoles

The reaction of isocyanoacetamide with N-sulfonylimine gives a novel double addition product in the absence of acid, base and catalyst to form 2,4-disubstituted-5-amino-1, 3-oxazole. A possible mechanism of this reaction is discussed.

Calculation of retention indexes of alkyloxazoles and alkylthiazoles in capillary chromatography

The retention indexes of 41 alkyloxazoles and alkylthiazoles have been determined at 110°C on capillary columns with OV-101/KF, Triton X-305/KF, and PEG-40M/KF, and the contributions calculated to the retention indexes of the methyl, ethyl, and propyl groups at different positions in the rings. The magnitude of the contribution for each alkyl group depends on its position in the ring; this has been used in the calculation schemes to predict the retention indexes of di- and trisubstituted oxazoles and thiazoles with different alkyl radicals.

Metalation studies of trisubstituted oxazoles

Metalation studies of trisubstituted oxazoles

Intermediates in the reaction of singlet oxygen with trisubstituted oxazoles

AbstractTrisubstituted oxazoles I react at −15° with singlet oxygen to give dioxazoles III and iminoanhydrides V which rearrange at room temperature to triamides VI. The intermediate ratio (III/V) is sensitive to the reaction temperature. It is likely that at room temperature triamides VI are essentially formed via imino‐anhydrides V.