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The invention discloses a simple and efficient synthesis method of a 2, 4, 5-trisubstituted oxazole compound, which comprises the following steps: adding a cyano-substituted ester compound, simple aromatic hydrocarbon, palladium acetylacetonate and dimeth

An efficient and straightforward protocol for the assembly of the pharmaceutically and biologically valuable oxazole skeleton is achieved for the first time from readily available simple arenes and functionalized aliphatic nitriles. This transformation in

The ultrasound assisted facile, rapid and one-pot synthesis of 2-aryl substituted 4,5-diphenyloxazoles was achieved via the reaction of commercially available benzoin (or 2-hydroxy-2-phenylacetophenone) with benzylamines in the presence of IBX under mild conditions. The methodology involved initial IBX mediated conversion of benzoin to benzil and then reaction with benzylamine followed by intramolecular cyclization (C[sbnd]O bond formation) and finally aromatization in the presence of air in the same pot. The methodology afforded a variety of desired products that were assessed for their cytotoxic properties against a number of cancerous and a non-cancerous cell lines. Compounds 3h, 3n and 3o showed promising growth inhibition of these cell lines except the non-cancerous one and interactions with SIRT1 in silico as well as in vitro.

A novel and efficient iron-catalyzed cycloaddition reaction using readily available 2,3-diaryl-2H-azirines and primary amides is reported. A wide range of trisubstituted oxazoles could be achieved in good yields with good functional group compatibility. In this transformation, two C-N bonds were cleaed and new C-N and C-O bonds were formed.

We have developed the visible light induced simple copper(ii) chloride catalyzed oxidation of diarylacetylenes to α-diketones by molecular oxygen at room temperature. The in situ generated copper(ii)-superoxo complex is a light-absorbing species that oxidizes inert diarylacetylenes to α-diketones. In contrast to reported photochemical processes, the current oxidation protocol does not require any exogenous photocatalyst or radical initiator. The green chemistry metrics evaluation signifies that the E-factor for the current oxidation process is ～2.3 times better than that of reported photochemical processes. The current reaction scores 63 on the EcoScale of 0-100, indicating an adequate synthesis process. Thus, the overall oxidation process is simple, environmentally benign, and economically feasible. This journal is

A palladium-catalyzed tandem reaction of cyanomethyl benzoates with arylboronic acids has been achieved. Substitution at the 2-position of cyanomethyl benzoates was found to be crucial for the selective synthesis of oxazoles and isocoumarins. Cyanomethyl

With the aim of developing a facile and efficient method to access structurally intriguing and valuable functionalized (hetero)aryls, two unsymmetrical Pd-PEPPSI-type NHC complexes (PEPPSI, pyridine-enhanced precatalyst preparation, stabilization, and initiation; NHC, N-heterocyclic carbene) were designed and synthesized to catalyze the direct arylation of heteroarenes with (hetero)aryl bromides. The results demonstrated that the utilization of this "unsymmetrical"strategy led to much higher efficiency in comparison to the commonly used C2-symmetric Pd-PEPPSI-type NHC complexes. Furthermore, a broad range of heteroaromatics and (hetero)aryl bromide partners with a wide variety of functional groups were all amenable to the developed protocol even at as low as 0.05 mol % catalyst loading and under aerobic conditions. More importantly, along with our study, we also found that the present protocol could provide expedient access to the gram-scale synthesis of the muscle relaxant drug dantrolene and conjugated mesopolymers.

The properties of C?F bonds, including high thermal and chemical stability, make derivatization of organic fluorine-containing compounds by the activation of the C?F bond and subsequent functionalization quite challenging. We herein report a Lewis acid-mediated defluorinative cycloaddition/aromatization cascade of 2,2-difluoroethanols with nitriles as a novel synthetic method for the preparation of 2,4,5-trisubstituted oxazoles. This reaction, which involves cleavage of two C?F bonds and the consecutive formation of C?O and C?N bonds in a one-pot fashion, features a broad substrate scope and moderate to high reaction yields. Mechanistic studies revealed that the reaction is initiated by the Lewis acid-mediated ring closure of the 2,2-difluoroethanol to produce the fluoroepoxide intermediate. (Figure presented.).

A new methodology has been developed for the synthesis of highly substituted nitrogen heterocycles such as pyrazines and imidazoles starting from α-diketones using phosphine supported ruthenium nanoparticles (RuNPs) as catalysts. Ruthenium nanoparticles Ru1-Ru4 supported with different phosphines such as dbdocphos, dppp, DPEphos, and Xantphos are screened, of which Ru1 and Ru4 are found to be the most active. Interestingly, aryl-substituted and alkyl-substituted α-diketones produced different products: namely, pyrazine and imidazoles, respectively. This reaction methodology has been applied to the synthesis of a key intermediate (2m) of the marine cytotoxic natural product Dragmacidin B and an estrogen receptor (2l). This work represents the first examples of pyrazines prepared by RuNPs.

Recent years have witnessed the significant role of anion-π+ interactions in many areas, which potentially brings the opportunity for the development of aggregation-induced emission (AIE) systems. Here, a new strategy that utilized anion-π

A directing-group-controlled, copper-catalyzed divergent approach to indoles and oxazoles from enamides has been developed. The picolinamide-derived enamides undergo the intramolecular aromatic C-H amination in the presence of a Cu(OPiv)2 catalyst and an MnO2 oxidant to form the corresponding indoles in good yields. On the other hand, simpler aryl- or alkyl-substituted enamides are converted to the 2,4,5-trisubstituted oxazole frameworks via vinylic C-H alkoxylation under identical conditions. The copper catalysis can provide uniquely divergent access to indole and oxazole heteroaromatic cores of great importance in medicinal and material chemistry.

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.

A simple and practical method for the synthesis of substituted oxazoles has been developed using readily available α-bromoketones and benzylamines by visible-light photocatalysis at room temperature. The process, which requires 1 mol % of [Ru(bpy)3]Cl2 photocatalyst with K3PO4 and CCl3Br, is effective for accessing a variety of valuable oxazole compounds. The synthetic utility of our protocol was also demonstrated by preparing a natural product, texaline.

A novel [3 + 2] cycloaddition/oxidative aromatization sequence via visible light-induced photoredox catalysis is disclosed. It provides a general synthetic route to 2,4,5-trisubstituted oxazoles from easily accessible 2H-azirines and aldehydes under mild reaction conditions. The potential of this strategy was further demonstrated by the rapid synthesis of a cyclooxygenase-2 inhibitor as well as the success of employing electron-deficient alkenes and imines as the reaction partners.

This is a silver(I) mediated Cα(sp3)H activation of primary amines followed by oxidative CO cross coupling/cyclization for the construction of 2,4,5-triaryl and 2-alkyl-4,5-diaryl oxazole derivatives. The protocol has been successfully utilized to synthesize the oxazole derivatives in good to excellent yields. In this oxidative coupling, the silver species after the reaction was successfully re-synthesized and reused with almost a similar activity.

An unusual trimerization of aldehydes in the presence of cyanide via metal-free aerobic oxidative esterification under ambient conditions is described. Various aromatic aldehydes provided the corresponding oxidative esterification products in good to excellent yields. Mechanistic studies suggested that this reaction would proceed via a two-step sequence: cyanide-catalyzed benzoin condensation of aldehydes and subsequent aerobic oxidative esterification of aldehydes with the resultant benzoin products. The usefulness of this protocol was further demonstrated by converting the resulting trimeric products into other biologically important compounds.

A highly efficient method for the synthesis of oxazole derivatives from simple amides and ketones has been established via a Pd(II)-catalyzed sp2 C-H activation pathway in one step. The reaction is supposed to proceed through a C-N bond formation followed by a C-O bond formation closing the ring. Because of the simple and readily available starting materials, easy operation, and high bioactivity of oxazoles, this strategy can be broadly applied to medical chemistry.

The present invention provides non-peptide compounds of formula (I) wherein: X is -(C1-C8)allcyl-, aryl or -aryl(C1-C8)alkyl-; Y is -(C1-C8)alkyl- or absent; W is heteroaryl, (C3-C7)carbocycle or aryl, wherein any heteroaryl, (C3-C7)carbocycle or, aryl of W is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) Z1 groups; R1 is (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) groups selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, halo(C1-C3)alkyl, -CN, NO2, halogen, -ORa, -SRa, -S(O)2NRbRc, -NRbRc, -NRaCORd, -C(O)Ra, -C(O)ORa, and -C(O)NRbRc; R2 is (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)Jalkynyl or aryl, wherein aryl is optionally substituted with one or more (e.g. 1, 2, 3, 4 or 5) groups selected from (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)carbocycle, halo(C1-C3)alkyl, -CN, NO2, halogen, -ORe, -SRe, -S(O)2NRfRg, -NRfRg -NReCORh, -C(O)Re, -C(O)ORe and -C(O)NRfRg; I that mimic the streptococcal; SspB Adherence Region (BAR) and function as inhibitors of P. gingivalis adherence to streptococci. The invention also provides methods of making and using the inhibitors.

Preparation of new types of trisubstituted oxazoles is realized via chemoselective O-acylations and intramolecular Wittig reactions with ester functionalities using in situ formed phosphorus ylides as key intermediates. A plausible reaction mechanism for this undiscovered chemistry is also proposed based on the existence of expected and rearranged isomeric oxazoles.

The reagent system of I2/K2CO3 could efficiently promote the oxazole synthesis from α-bromoketones and benzylamine derivatives in DMF. This method was not only suitable for 2,5-diaryl oxazole synthesis but also for 2,4,5-trisubstituted oxazole and 5-alkyl/alkenyl oxazole synthesis. Furthermore, this method was successfully applied to a one-step synthesis of a natural product halfordinol in 62% yield.

A facile CuI-catalyzed and air promoted oxidative cyclization was developed for the synthesis of polyarylated oxazoles. By virtue of this method, a variety of arylated oxazoles could be easily synthesized from readily available starting materials at room temperature in air. The Royal Society of Chemistry 2013.

A series of nine metal chloride hydrates (ZnCl2.2H2O, SnCl2.2H2O, CdCl2.2H2O, MnCl 2.4H2O, CoCl2.6H2O, SrCl 2.6H2O, NiCl2.6H2O, CrCl 3.6H2O and CeCl3.7H2O) was investigated as mild and inexpensive Lewis acid catalysts to promote the multicomponent synthesis of triarylimidazoles. Reactions starting from benzil showed the best results when SnCl2.2H2O was used, while for benzoin as the starting material, CeCl3.7H2O was more efficient. All reactions were performed in EtOH as solvent. These catalysts were also successfully employed in the synthesis of triaryloxazoles.

A series of azidoaryl- and azidoalkyl(diphenyl)oxazole scaffolds were warranted for biofilm inhibition studies. Cyclization of azidoaryl- or azidoalkyl esters of benzoin with ammonium acetate in acetic acid gives 2-azidoaryl- or 2-azidoalkyl-4,5-diphenyloxazoles. The azidoaryl esters are prepared from the corresponding azidocarboxylic acids/acid chlorides while the azidoalkyl esters are prepared from the corresponding haloalkyl esters.

Direct triarylation and sequential triarylation reactions of simple azoles catalyzed by [Pd(phen)2]PF6 are described. Simple azoles, such as N-methylimidazole, thiazole, and oxazole, were observed to undergo triaryaltion reactions even at their C4 positions when treated with aryl iodides in the presence of [Pd(phen)2]PF6 as a catalyst and a stoichiometric amount of Cs2CO3 in DMA at 150 °C. Using excess amounts of azoles, selective C5 monoarylation was achieved by using the same catalytic system. Subsequent efforts demonstrated that C5 arylated azoles undergo exclusive C2 arylation using [Pd(phen)2]PF6 as the catalyst with galvinoxyl as an additive. Finally, unprecedented C4 arylation reactions of 2,5-diaryl-azoles occur by using the new catalytic system to give the corresponding triarylated products in good to excellent yields. The results of mechanistic studies suggest that the C2 arylation process takes place by way of an electrophilic aromatic substitution (SEAr) palladation pathway, while arylation reactions at the C4 position occur via a SEAr palladation and/or radical mechanism. Finally, a concise, three-step synthesis of the Tie-2 Tyrosine Kinase Inhibitor has been executed starting with commercially available N-methylimidazole by a route that employs the new sequential arylation process.

A series of 2,4,5-triarylimidazoles was synthesized from a new, highly efficient and green method. The reaction is performed in water, without the presence of any catalyst, and under microwave irradiation. This provides new opportunities for the rapid scr

A facile type of one-pot, transition-metal-free domino process was developed for the synthesis of oxazoles. Thus, a variety of polysubstituted oxazoles were easily synthesized via t-BuOOH/I2-mediated domino oxidative cyclization from readily available starting materials under mild conditions.

The Lewis acid catalyzed Ritter reaction of α-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. Georg Thieme Verlag Stuttgart.

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.

A study was conducted to demonstrate the synthesis of tetrasubstituted imidazoles and trisubstituted oxazoles by aldimine cross-coupling reaction. The method involved 1,2-addition of easily available deprotonated N-monosubstituted α-aminotitriles to aldim

Conditions for the palladium-catalyzed direct arylation of a wide range of heterocycles with aryl bromides are reported. Those conditions employ a stoichiometric ratio of both coupling partners, as well as a substoiehiometric quantity of pivalic acid, which results in significantly faster reactions. An evaluation of the influence of the nature of the aryl halide has also been carried out.

A variety of oxazoles can efficiently be prepared, in a single step and in good yield, from primary amides and 1,2-dihaloalkenes using copper-catalysis. This new method allows the regioselective formation of a range of substituted oxazoles. The required 1,2-dihaloalkenes can prepared by simple treatment of alkynes with elemental bromine or iodine. Georg Thieme Verlag Stuttgart.

A novel method for the direct conversion of deoxybenzoin into 2-alkyl-4,5-diphenyloxazoles and 2-aryl-4,5-diphenyloxazoles has been developed using treatment of HTIB and nitriles under solvent-free microwave irradiation conditions. Copyright Taylor & Fran

We report herein a one-pot synthesis of 2,4,5-trisubstituted oxazoles via a Friedel-Crafts/Robinson-Gabriel synthesis using a general oxazolone template. Treatment of the oxazolone template with a range of aromatic nucleophiles provided the highly substituted oxazoles in good yields.

Thiazole, 2-phenyl or -alkyl substituted one and benzothiazole are efficiently arylated with aryl bromides at the 2- and/or 5-position(s) in the presence of Pd(OAc)2 and a bulky phosphine ligand using Cs2CO3 as base. 2-Phenyl-5-thiazolecarboxanilide undergoes successive diarylation at the 4- and 5-positions accompanied by decarbamoylation.

A new and efficient method for the synthesis of multi-substituted oxazoles from various carbonyl compounds has been developed using sequential treatment of carbonyl compounds with HDNIB and amides such as acetamide or benzamide under solvent-free microwave irradiation conditions.

(formula presented) R1 = Ar, Het, alkenyl R2 = H, Ar, Het, alkenyl, alkynyl R3 = H, CO2H, Ar, Het, alkenyl, alkynyl By using a sequence of regiocontrolled halogenation and palladium-catalyzed coupling reactions,

A process for the preparation of oxazoles of formula (II): by reaction of thiourea with the corresponding diketone ester.

Treatment of ∝-benzoinoxime (4) with stable phosphorus ylides 5a,bin dioxane gives oxazolines 8a,b, oxazinone-19 and hydroxyfuran 22, whereas in benzene besides 8a,b, the isoquinoline 16 is obtained. Performing the reaction of 4 and 5a,b in toluene, besides 8a,b, the oxazole 10a and the oxazines 12a,b are obtained. Compound 4, on treatment with a phosphonium salt of the semi-stabilized allylic ylide 23a affords 1-hydroxypyrrole 25a and 2-hydroxy isoquinolidene 27, while with phosphonium salts of the reactive ylides 23b,c gives the imines 29a,b along with the ylides 31 or 33, respectively.

The synthetic methods to prepare 2-alkyl(aryl)-4,5-diphenyloxazoles and 2-alkyl(aryl)-4-phenyloxazoles were improved on the basis of a mechanistic study of oxazole formation from α-hydroxy ketones (carboxylic esters of benzoin and phenacyl alcohols). By these methods, seven trisubstituted oxazoles and twelve disubstituted oxazoles of the title compounds were prepared.

N-Acylisoxazol-5-ones lose carbon dioxide under photochemical and thermal conditions affording iminocarbenes which undergo intramolecular cyclisation through the oxygen of the acyl group to give oxazoles. Under photochemical conditions those acylisoxazolones with electron withdrawing groups at C-4 usually give high yields of oxazoles, while those with electron donating groups at C-4 give only poor yields: the reverse is observed under thermal conditions.

23 tetraphenylimidazoles 1,2 and 11 triphenyl-oxazoles 4,5 with amino, nitro, methoxy, hydroxy, or halogeno substituants chiefly in the para position were prepared. The absorption and fluorescence emission properties were investigated in ethanolic solution. The effects of the substituents in 1,2 on the spectral shifts show that the arrangement of the phenyl rings in 1 position is not coplanar in relation to the heterocycle whereas the phenyl rings in 2 position are more coplanar. The spectral changes of compound 2a in solvents of various polarity (dielectric constants 2,02-47,24) are almost negligible. The Stokes shift is moderately increased. A remarkable increase in the fluorescence quantum yield is observed by chlorine substitution in phenyl ring 2.

Reactions of benzils and urea in ethylene glycol at 180° for 1-2 hours gave 2,4,5-triaryloxazoles as major products and bicyclic imidazoimidazole-2,5-diones as minor products. N-Methylurea and W-phenylurea gave the oxazoles under similar conditions. The solvent seemed to assist the formation of oxazole by eliminating the isocyanate components as ethylene glycol biscarbamates.

N-acylisoxazol-5-ones are converted into the corresponding 2-substituted oxazoles by photolysis at 300 or 254 nm, or by flash vacuum pyrolysis. The former procedure is favoured for isoxazolones with electron withdrawing groups at C-4, and pyrolysis for all others.

Contrary to ethoxycarbonylnitrene, selective reactions - including cycloadditions - can be carried out with benzoylnitrene. This study analyzes the sequence of reactivity of various bond types with respect to benzoylnitrene, which was generated by three different routes: direct photolysis of benzoyl azide, sensitization of azide decomposition via energy transfer, and photoinduced electron transfer. In all cases the same cycloadducts 23, 24, and 30 were obtained. Carbonyl activity determines the reactivity of unsaturated ketones and aldehydes with respect to benzoylnitrene.

The reaction between desylchloride and sodium azide in boiling methanole leads to 2,4,5-triphenyloxazole (TPO) c in good yields.This new synthetic course can be used for the synthesis of other triaryl substituted oxazoles too.The shortlived excited single

The 2-azaallenyl complex LnM--C(Ph)=N+=C(Ph)OCO-Ph 3 nM=Cr(CO)5> adds to the 1-aminopropyne Et2N-CC-CH3 (4) to give the aminocarbene complexes LnM=C(NEt2)-C(CH3)=C(Ph)-N(COPh)2 and LnM=C(NEt2)-C(CH3)=C(Ph)-NH(COPh) (by insertion of 4 into the M=C bond of 3) as well as a 1,3-diaminoindene 6 (by cycloaddition).An iminocarbene complex LnM=C(Ph)-N=C(Ph)-O-C(Ph)=C(CH3)-CONEt2 (7) is formed as a further product (by insertion of 4 into the C=O bond of 3).The latter type of reaction can also be applied to metal-free carbonyl compounds: thus phthalic anhydride reacts smoothly with 4 to give a γ-lactone 12 and a 1,3-indanedione 13 by insertion of 4 into a C=O and C-O bond, respectively.The thermolysis of the iminocarbene complex 7 yields a cyclopropane derivative 14 by an intramolecular attack of the carbene carbon at the (O)C=C bond.The structure of 14 has been determined by a crystal structure analysis.On thermolysis of 3 a triphenyloxazole 15 is obtained.The mechanisms of these reactions are discussed.

The results of our studies on potassium-induced transformations of some selected nitrogen heterocycles are presented.The substrates under investigation include 2,3-diphenylindole (1a), 2,3-diphenyl-1-methylindole (1b), 1,2,3-triphenylindole (1c), 2,3,4,5-tetraphenylpyrrole (5a), 1,2,3,5-tetraphenylpyrrole (5b), 1-benzyl-2,3,5-triphenylpyrrole (5c), 2,4,5-triphenyloxazole (15a), 4,5-diphenyl-2-methyloxazole (15b), 2,4-diphenyl-5-methyloxazole (15c), and 2,4,5-triphenylimidazole (19).Treatment of 1a with potassium in THF gave 9H-dibenzocarbazole (3a), whereas 1c gave a mixture of 9-phenyl-9H-dibenzocarbazole (3c) and 2,3-diphenylindole (1a).Under identical conditions, 1b gave only the cleavage product 1a.In contrast, when the reactions of 1a,c were carried out with potassium in THF saturated with oxygen, and with potassium superoxide in benzene containing 18-crown-6, a mixture of 2-benzamidobenzophenone (4a), the carbazoles 3a,c, and 1a was formed.Although no product was isolated on treatment of 5a with potassium in THF, the reaction of 5a with potassium in THF saturated with oxygen gave a mixture of tetraphenylpyrazine (7a), the benzoylaminostilbene 8a, the lactam 12a, benzamide (11a), and benzoic acid (14).Similar results were obtained in the reaction of 5a with potassium superoxide.The reaction of N-substituted pyrroles such as 5b,c with potassium gave the NH pyrrole 9b in each case, whereas the reaction of 5b,c with potassium in THF, saturated with oxygen, gave a mixture of 9b, the butanone 10b, the 1,4-dione 13b, the lactam 12b, the amides 11a-c, and benzoic acid (14).Attempted reactions of 5b,c with potassium superoxide did not give any isolable product; most of the starting material could be recovered unchanged in each case.A mixture of N-(1,2-diphenylethyl)benzamide (18a) and benzoic acid (14) was formed in the reaction of the oxazole 15a with potassium, whereas 15b,c, under analogous conditions, gave the N-vinylamides 17b,c and benzoic acid (14).In contrast, treatment of the imidazole 19 with potassium in THF did not give any product; however, when the reaction of 19 was carried out with potassium in THF saturated with oxygen, and with potassium superoxide, dibenzamide (21) was isolated, in each case.Radical ions have been invoked as intermediates in the transformation of the different substrates to the observed products.Cyclic voltammetric studies have been carried out to measure the reduction potentials of these radical anion intermediates.These radical anions have also been generated by pulse radiolysis in methanol, and their absorption spectra recorded.

The readily obtainable products from the condensation of arylglyoxals with carboxamides react with benzene and its analogs in the presence of concentrated sulfuric acid or phosphorus pentoxide in trifluoroacetic acid with the formation of arylmethyl aryl ketones, which are used for the synthesis of substituted azoles.

An investigation of the reaction of variously substituted oxazoles 1a-1 with Br2 in methanol revealed the formation of non-aromatic addition products.In general the presence of an aromatic substituent at the 4-position of oxazoles or the presence of a 4-methyl group if the 2-substituent is also aliphatic favors formation of 2,5-dimethoxy-3-oxazolines 3, while an aromatic substituent at the 2-position favors formation of ring-opened amides 2 or 7 or of 4,5-dimethoxy-2-oxazolines 5.Valuable information about intermediates in these reaction can be obtained by following the bromination of 1 in CD3OD by 1H- and 13C-NMR.