Synthesis Of Oxazoles Research Articles

Preparation of oxazolines and oxazolesviaa PhI(OAc)2-promoted cyclization ofN-propargylamides

A metal-free cyclization of N-propargylamides for the synthesis of various oxazolines and oxazoles via a 5-exo-dig process is presented. Using (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N-propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in the presence of oxygen under visible light irradiation. The resulting products can be further converted into various oxazoline and oxazole derivatives after simple derivatizations, and this method ultimately offers an efficient route to a variety of biologically active structures.

Improvement of the Van Leusen reaction in the presence of β-cyclodextrin: a green and efficient synthesis of oxazoles in water

Abstract An efficient approach for the synthesis of oxazoles through the Van Leusen reaction in the presence of β-cyclodextrin is described. In aqueous medium using β-cyclodextrin as a supramolecular catalyst, tosylmethyl isocyanide was deprotonated by triethylamine and subsequently underwent an addition/cyclization reaction with aldehydes to produce corresponding oxazoles in excellent yields. This protocol improves the Van Leusen reaction with the use of catalytic amounts of base at low temperature in green media.

Synthesis of Imidazoles, Thiazoles, and Oxazoles by Using Hydrotalcite

Synthesis of Imidazoles, Thiazoles, and Oxazoles by Using Hydrotalcite

Synthesis and Photophysical Properties of C 3-Symmetric Star-Shaped Molecules Containing Heterocycles Such as Furan, Thiophene, and Oxazole.

We report simple strategies to synthesize star-shaped molecules containing different heterocycles integrated with a number of variations. Here, cyclotrimerization, Vilsmeier–Haack reaction, Suzuki–Miyaura cross-coupling, and Van Leusen oxazole synthesis have been used as key steps to introduce diverse five-membered heterocycles such as furan, thiophene, and oxazole. More importantly, readily available starting materials such as thiophene, 2-formyl furan, and 2-acetyl furan were utilized. Also, the fluorescent behavior of these π-conjugated systems was studied. C3-Symmetric molecules containing furan moieties show a stronger fluorescence than thiophene-containing star-shaped compounds.

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid.

A novel method for the synthesis of trisubstituted oxazoles via a one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding 2,4,5-trisubstituted oxazoles in good yields.

Mechanistic Pathways in Amide Activation: Flexible Synthesis of Oxazoles and Imidazoles.

The preparation of substituted aminooxazoles and aminoimidazoles from α-arylamides and α-aminoamides through triflic anhydride-mediated amide activation is reported. These reactions proceed via the intermediacy of nitrilium adducts and feature N-oxide-promoted umpolung of the α-position of amides as well as a mechanistically intriguing sequence that results in sulfonyl migration from nitrogen to carbon. Quantum-chemical mechanistic analysis sheds light on the intricacies of the process.

Metal-free syntheses of oxazoles and their analogues based on λ3-iodane-mediated cycloisomerization/functionalization reactions or [2+2+1] cycloaddition type reactions

Metal-free syntheses of oxazoles and their analogues based on λ3-iodane-mediated cycloisomerization/functionalization reactions or [2+2+1] cycloaddition type reactions

Multifunctional odorless isocyano(triphenylphosphoranylidene)-acetates: synthesis and direct one-pot four-component Ugi/Wittig cyclization to multisubstituted oxazoles

A new one-step four-component synthesis of multisubstituted oxazoles has been developed.

Readily switchable one-pot 5-exo-dig cyclization using a palladium catalyst

A convenient, ligand-free, Pd(OAc)2-catalyzed one-pot reaction has been developed for the synthesis of oxazolines and oxazoles from easily available acid chlorides and propargylamine.

Synthesis of fluorescent trisubstituted oxazoles via a facile tandem Staudinger/aza-Wittig/isomerization reaction

A new facile synthesis of trisubstituted oxazoles starting from azides was developed. The reactions of azides with triphenyl phosphine afforded the corresponding 2,4,5-trisubstituted oxazole derivatives via tandem Staudinger, aza-Wittig and isomerization reaction either thermally or under basic conditions. Properties of the oxazole derivatives were surveyed and some of the examples showed reasonable fluorescence. The greatest fluorescence intensity was observed when the 2- and the 5- substituents on the oxazole ring were aromatic groups (with ε = 2.3–3.0 × 104 mol−1 dm3 cm−1 and Φ = 0.25–0.29 relative to quinine sulphate). However, the fluorescence intensity was diminished when either the 2- or the 5-substituent was H or alkyl.

ChemInform Abstract: The Synthesis of Pyrroles and Oxazoles Based on Gold α‐Imino Carbene Complexes.

AbstractCationic gold complexes of α‐oximimino carbenes react with weak nucleophiles including enol ethers and nitriles to provide the highly efficient synthesis of pyrroles and oxazoles.

Safe and Fast Flow Synthesis of Functionalized Oxazoles with Molecular Oxygen in a Microstructured Reactor

The synthesis of hydroperoxymethyl oxazoles by oxidation of alkylideneoxazoles with molecular oxygen was implemented in a microstructured reactor for increased safety and larger-scale applications. Elaborate studies on the influence of pressure and temperature were performed, and the apparent activation energy for the oxidation reaction was determined. Elevated temperatures up to 100 °C and pressures up to 18 bar(a) led to a conversion rate of approximately 90% within 4 h of the reaction time, thus displaying the high potential and beneficial effect of using a microreactor setup with liquid recycle loop for this oxidation. The in situ reduction of the generated hydroperoxide functionality shows the capability of this setup for follow-up transformations.

Magnesium-Catalyzed Enantioselective Synthesis of Oxazoles

Magnesium-Catalyzed Enantioselective Synthesis of Oxazoles

Frontispiece: Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N‐Substituted 2‐Oxazolones

Frontispiece: Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from <i>N</i>‐Substituted 2‐Oxazolones

Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N-Substituted 2-Oxazolones.

A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis.

ChemInform Abstract: Synthesis of Oxazoles by Tandem Cycloisomerization/Allylic Alkylation of Propargyl Amides with Allylic Alcohols: Zn(OTf)2 as π Acid and σ Acid Catalyst.

A Zn(OTf)2-catalyzed tandem cycloisomerization/allylic alkylation of N-(propargyl)arylamides and allylic alcohols to produce oxazole derivatives has been successfully developed. The zinc catalyst served as π acid and also σ acid in this reaction. The target allylic oxazoles have been transformed into multisubstituted diene structures, which are potential aggregation-induced emission active optical materials.

ChemInform Abstract: Metal‐Free sp3 C—H Functionalization: PABS/I2‐Promoted Synthesis of Polysubstituted Oxazole Derivatives from Arylethanones and 2‐Amino‐2‐alkyl/arylacetic Acid.

A nonmetal-catalyzed process for the synthesis of polysubstituted oxazoles from inexpensive and readily available α-amino acids and methyl ketones is established. This reaction is proposed to achieve oxidative cleavage of C(sp3)–H bonds, followed by decarboxylation and annulation. The mild reaction conditions employed in both cases enable the tolerance of a wide range of functional groups as well as high reaction efficiency.

Synthesis and antifungal activity of bile acid-derived oxazoles

Peracetylated bile acids (1a–g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a–g, 8a–g). The key step for the synthetic path was a Dakin–West reaction followed by a Robinson–Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a–g) as well as their starting bile acids (1a–g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250μg/mL respectively). Deacetylation of compounds 6a–g, led to compounds 8a–g which showed lower activities than the acetylated derivatives.

Efficient and Flexible Synthesis of Highly Functionalised 4‐Aminooxazoles by a Gold‐Catalysed Intermolecular Formal [3+2] Dipolar Cycloaddition

AbstractOxazoles are important motifs within bioactive and functional materials. Complex, fully substituted and functionalised 4‐aminooxazoles are accessed by an efficient intermolecular reaction between an ynamide and an N‐acylpyridinium N‐aminide in the presence of a gold catalyst. The formal [3+2] dipolar cycloaddition employs a nucleophilic nitrenoid approach to access the 1,3‐N,O‐dipole character in a controllable fashion. The selectivity for a cycloaddition pathway provides a stark contrast against the indiscriminate reactivity of electrophilic acyl nitrenes. Protocols for the formation of acyl‐functionalised aminides are reported from accessible precursors including carboxylic esters and acids. The function of these aminides in the oxazole‐forming reaction has been explored and it is shown that substantial elaboration is accommodated despite proximity to the reactive centre. As a result functional oxazole‐based motifs, such as chiral oxazoles with biologically pertinent substitution patterns, are readily accessible. The use of ynamide types that are unexplored or little used in gold catalysis has been evaluated. Unusual all‐heteroatom substitution patterns around the oxazole are shown to be accessible using thio‐ynamides. The study shows that a close stoichiometry of reactants is suitable alongside relatively low loadings of the bench‐stable precatalysts in practically straightforward multi‐mmol scale reactions. The efficiency and flexibility of this regioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.magnified image

ChemInform Abstract: [3 + 2] Cycloaddition/Oxidative Aromatization Sequence via Photoredox Catalysis: One‐Pot Synthesis of Oxazoles from 2H‐Azirines and Aldehydes.

AbstractA novel [3 + 2] cycloaddition/oxidative aromatization sequence via visible light‐induced photoredox catalysis is described.