Experimental and theoretical investigation of new furan and thiophene derivatives containing oxazole,isoxazole, or isothiazole subunits

Structural Chemistry - Herein, we present joint experimental and theoretical studies on newly designed thiophene- or furan-based oxazole, isoxazole, and isothiazole derivatives. Our synthetic...     

Opening of azole rings by reagents that contain amino groups

Data on the opening of oxazole, isoxazole, thiazole, isothiazole, pyrazolidine, and imidazolidine rings (particularly the rings of oxo derivatives) by amines, amino acids and their derivatives, hydrazines, and hydroxylamine are correlated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1587–1597, December, 1979.Original article submitted January 23, 1979.     

Adsorption mechanisms of isoxazole and oxazole on Si(100)-2 × 1 surface: Si-N dative bond addition vs. [4+2] cycloaddition

The surface reaction pathways of isoxazole and oxazole on Si(100)-2 × 1 surface were theoretically investigated. They both form a weakly bound Si-N dative bond adduct on Si(100)-2 × 1 surface. In the case of isoxazole, the barrierlessly formed Si-N adduct is the most important surface product, that cannot be easily converted into other species. On the other hand, a facile concerted [4+2](CC) cycloaddition without involving the initial Si-N dative bond adduct was also found in the case of oxazole adsorption. The existence of Diels-Alder reactions is attributed to the particular arrangement of the two heteroatoms of oxazole in such a way that the two Si-C σ-bonds can be formed in a [4+2] fashion. In short, the unique geometric arrangements and electronegativity of these similar heteroatomic molecules yielded distinctively different surface reaction characteristics.     

A synthetic pathway to obtain heterocyclic derivatives containing isoxazole and tetrazole rings joined by a carbohydrate tether

A synthetic route to obtain compounds with two different heterocycles, such as isoxazole and tetrazole rings, in the same molecule from carbohydrate derivatives using 1,3‐dipolar cycloaddition is described. The new compounds involved in this synthesis are physically and spectroscopically characterized.     

Catalytic asymmetric cyclopropanation of heteroaryldiazoacetates

Rh(2)(S-DOSP)(4)-catalyzed decomposition of heteroaryldiazoacetates in the presence of styrene results in highly diastereoselective and enantioselective cyclopropanations. Heteroaryldiazoacetates containing both electron-rich and electron-deficient heterocycles, such as thiophene, furan, pyridine, indole, oxazole, isoxazole, and benzoxazole, are effective in this chemistry. These studies broaden the range of diazo compounds containing both electron-withdrawing and electron-donating groups, which undergo highly diastereoselective cyclopropanations.     

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

A series of new 1,3‐oxazole derivatives, containing in position 5 both donor and acceptor substituents were synthesized. These substances were considered as potentially active anticancer pharmacophores in the human tumor cell line panel derived from nine cancer types, including lung, colon, melanoma, renal, ovarian, brain, leukemia, breast, and prostate. Primary in vitro one‐dose anticancer screening was shown that compounds with acceptor substituents (such as –C(O)OMe, –CN) in the position 5 inhibit the growth of most cell lines, and compounds with donor substituents (such as –NHR, ?SR) in the position 5 do not practically inhibit the growth of cancer cell lines. It can be assumed that the pharmacological activity of 1,3‐oxazole derivatives depends on donor/acceptor nature of the substituents in position 5. It was proposed to evaluate the donor/acceptor ability of 1,3‐oxazole derivatives using the special parameter φ₀, which takes into account the relative position of the boundary levels (HOMO end LUMO). The quantum‐chemical modeling was performed; the special parameter φ₀ for 1,3‐oxazole derivatives correlates with the experimental results. Quantum‐chemical calculations of the special parameter φ₀ allow modeling the pharmacological activity of 1,3‐oxazole derivatives by introducing donor or acceptor substituents at position 2 or 5. This work may be useful for chemists to develop a target synthesis of potential biologically active compounds.     

Spectrométrie de Masse D'Hétérocycles Azotés. VI—Tautomérie en Phase Gazeuse d'Isoxazolones-5

A comparison of the fragmentation under electron impact of isoxazol-5-ones with those of their methylated derivatives (5-methoxy isoxazoles, 2-methyl isoxazol-5 ones and 4-4-dimethyl isoxazol-5 ones) shows that in the vapor phase and prior to the fragmentation, the isoxazol-5 ones exist in the CH tautomeric form. Furthermore, in the case of the 5-methoxy isoxazoles, it has been established that the rearrangement isoxazole→azirine→oxazole which occurs thermally, leads to a variation in the intensities of some ions depending on the experimental conditions.     

Overview on Recent Approaches towards Synthesis of 2‐Keto‐annulated Oxazole Derivatives

In recent years, oxazole derivatives have emerged as one of the formidable groups of compounds in the field of medicinal chemistry and drug discovery. The titled compounds 2‐keto‐annulated oxazoles play an important role towards the medicinal aspects. There has been an appearance of a significant number of research articles and reviews to explore the wide utility of oxazole derivatives. However, till now, there has been no dedicated review published focusing on the synthesis of 2‐keto‐annulated oxazole derivatives. Herein, we have presented the recent protocols available in literature for the synthesis of 2‐keto‐annulated oxazoles and highlighted the advantages of these methods that would attract the attention of a broad range of readers in the chemistry community.     

Convergent integration of two self-labor domino sequences: a novel method for the synthesis of oxazole derivatives from methyl ketones and benzoins

A highly efficient method for the synthesis of oxazole derivatives from methyl ketones, benzoins and ammonium acetate has been established via a novel strategy-convergent integration of two self-labor domino sequences. Owing to the simple and readily available starting materials, mild reaction conditions, facile operation, and the high bioactivity of oxazole derivatives, this reaction promises diverse applications in medical chemistry. Additionally, this reaction could provide an efficient example for self-labor synthesis strategy of organic compounds.     

Conjugation at the oligonucleotide level based on isoxazole phosphoramidites generated by click chemistry

The versatility of the isoxazole generating nitrile oxide-alkyne Huisgen cycloaddition for provision of chemically modified oligonucleotides has been extended; in a novel approach isoxazole conjugated oligodeoxyribonucleotides have been constructed by phosphoramidite chemistry of isoxazole derivatives previously generated by nitrile oxide-alkyne click chemistry. The conjugation involves manual solid phase synthesis at room temperature in aqueous ethanol and proceeds in high yield.     

2‐Arylhydrazono‐3‐oxopropanals in heterocyclic synthesis: Synthesis of arylazopyrazole,arylazoisoxazole and dialkylpyridazine‐5,6‐dicarboxylate derivatives. New one‐step synthesis of arylazopyrimidines

A novel synthesis of arylpyrazole, isoxazole, dialkyl 1,6‐dihydropyridazine 5,6‐dicarboxylate derivatives and a new one‐step synthesis of azolopyrimidines under microwave‐assisted conditions are reported.     

Zn/Y双金属接力催化:一锅法分子内环异构化/分子间阿尔德-烯反应构建α-羟基酰胺噁唑衍生物

报道了一种新型的Zn/Y双金属接力催化的串联反应,该方法通过Zn(OTf)2和Y(OTf)3接力催化,一锅法进行分子内环异构化/分子间阿尔德-烯反应构建α-羟基酰胺噁唑衍生物.产物的形成主要是由Zn(OTf)2活化炔丙基酰胺的叁键发生分子内的环化反应构建噁唑啉中间体,由Y(OTf)3催化1-苄基吲哚啉-2,3-二酮类化合物,继而由噁唑啉中间体与1-苄基吲哚啉-2,3-二酮类化合物发生分子间阿尔德-烯反应,实现了α-羟基酰胺噁唑衍生物的合成.优化部分的对比实验证实,Zn(OTf)2和Y(OTf)3的存在对于该串联反应都是必须条件.所有反应都是将各反应物和试剂一次性加入,在空气氛围下100℃加热进行反应.该方法反应条件简单、原子经济性高、官能团兼容性好,对噁唑衍生物合成具有重要的意义.     

Structural regularities governing sorption and gas chromatographic retention of aromatic nitrogen-containing heterocyclic compounds

The regularities governing differences in the gas chromatographic retention indices of aromatic nitrogen-containing heterocyclic compounds were studied during gas chromatographic analysis on a nonpolar capillary column. The retention indices of pyrrole, pyrazole, imidazole, 1,2,4-triazole, oxazole, thiazole, isoxazole, pyridine, pyridazine, pyrimidine, pyrazine, ands-triazine and their alkyl derivatives depend on the number, nature, and arrangement of heteroatoms and alkyl groups in the cycles. The majority of homologous series ofn-alkyl-substituted azoles and azines andn-alkylbenzenes is characterized by anomalously high differences between the retnetion indices of ethyl and methyl homologs. A scheme of calculation of retention indices of aromatic heterocyclic compounds from increments of heteroatoms was proposed.     

Aminophenyl-X-azolopyridines as precursors of heterocyclic azo dyes

Aminophenyl-X-azolopyridines (X = O, S, NH) are interesting intermediates for the synthesis of disperse azo dyes and, provided the pyridine nitrogen is quaternized, of their cationic counterparts. A set of novel amines and nitro derivatives is described, and their physical properties and spectral parameters are discussed in comparison with those of analogous compounds. Some dyes in the oxazole series function as probes of the reactivity of the pentatomic ring.     

A facile one-pot synthesis of 2-o-cyanoaryl oxazole derivatives mediated by CuCN

A convenient, inexpensive and effective approach to the synthesis of 2-o-cyanoaryl oxazole derivatives has been developed. Generally, the copper-mediated cyclization/coupling reactions afforded corresponding 2-cyanoaryl oxazoles and oxazolines in moderate to excellent yields. The functionalized oxazole derivatives may be useful in biological chemistry and medicinal science. Our investigation indicates that the formation of the oxazole ring might favor the CC bond forming process on the ortho-position of the aryl ring. And CuCN plays dual roles as a Lewis acid catalyst and a C-nucleophile in this transformation.     

A novel synthesis of 2,5-di-substituted pyridine derivatives by the ring opening and closing cascade (ROCC) mechanism

A new regioselective method for the synthesis of 2-aryl-5-benzoylpyridine derivatives has been developed. The reaction proceeds via ring opening and closing cascade mechanism (ROCC) of isoxazole to synthesize various functionalized pyridine derivatives. This is the first report for the preparation of 2,5-di-substituted pyridines using Fe/NH₄Cl as a reducing reagent.     

Catalyst-free synthesis of coumarin-, quinolone- and pyridine-annulated oxazole derivatives

An efficient approach for the synthesis of coumarin-, quinolone- and pyridine-annulated oxazole derivatives has been achieved by direct base-mediated intramolecular carbon–oxygen bond formation in a transition metal catalyst-free protocol. Intramolecular cyclization of o-bromoamides in DMSO in the presence of Cs₂CO₃ at 130 °C affords heterocycle-annulated oxazole derivatives in high yields via a nucleophilic addition of amide to form the C–O bond.     

Selected Methodologies Convenient for the Synthesis of N,5‐Diaryloxazole‐2‐amine Pharmacophore

N,5‐Diaryloxazole‐2‐amine moiety is a strong pharmacophore found in 775 biologically active compounds possessing antitumor, anti‐infective, immunosuppressive, anti‐inflammatory, and other activities. Despite a broad biological exploitation, synthesis of N,5‐diaryloxazole‐2‐amine‐containing compounds is still not well developed. Preparation of oxazole‐2‐amine moiety is a relatively complex topic, and often low yields are observed. In this article, we discussed four synthetic methodologies and provided some generalization of their advantages, as well as further synthetic development. Using these methodologies, we prepared all together 10 new oxazole‐2‐amine derivatives and discovered presence of urea and enamine side products.     

Studies on isoxazole and pyrazole formation by the reaction of trifluoromethyl-substituted anilines with oxime and hydrazone dianions

5-(2-Aminophenyl)isoxazoles are obtained in good yields by the reaction of 2-(trifluoromethyl)aniline with dilithio derivatives of oximes of acetone, 3-pentanone, propiophenone, and cyclohexanone. An analogous synthesis of a substituted isoxazole from 4-(trifluoromethyl)aniline and 3-pentanone oxime and the synthesis of a substituted pyrazole from 2-(trifluoromethyl)aniline and 3-pentanone hydrazone are less efficient.     

Substituent effects on 15N and 13C NMR chemical shifts of 3-phenylisoxazoles: a theoretical and spectroscopic study

The synthesis and assignment of 15N and 13C NMR signals of the isoxazole ring in a series of para-substituted 3-phenyl derivatives are reported. DFT calculations of 15N and 13C chemical shifts are presented and compared to observed values. Substituent effects are interpreted in terms of the Hammett correlation and calculated bond orders.