Facile Synthesis of 1,2-Disubstituted Benzimidazoles Usingp-Toluenesulfonic Acid through Grinding Method

Russian Journal of Organic Chemistry - An efficient synthetic method for the highly selective synthesis of pharmacologically active 1,2-disubstituted benzimidazole derivatives...     

A Facile Route to the Synthesis of New 2,3-Disubstituted Benzocoumarins

Triphenylphosphine catalyzes the reaction between 2-hydroxy-1-naphthaldehyde and π-deficient acetylenes to give the newly prepared benzo[f]chromenes. The mechanism for the formation of products is discussed.     

Synthesis and Conformation of cis-1,2-Disubstituted Cyclododecene

Eight 1,2-disubstituted cyclododecenes were synthesized from a-alkoxycarbonyl-cyclododecanone and alkyl chloroformate. Their configuration and conformation determined by IR, NMR spectroscopy and X-ray diffraction analysis showed that the carbon-carbon double bond of all of the synthesized compounds has cis-configuration, and the ring skeleton of their preferred conformation is [lene2333] in solid, and they may adopt two different [lene2333] conformations, which exist in a dynamic equilibrium in solution.     

Rhodium-Catalyzed Asymmetric Synthesis of 1,2-Disubstituted Allylic Fluorides

Although there are many methods for the asymmetric synthesis of monosubstituted allylic fluorides, construction of enantioenriched 1,2-disubstituted allylic fluorides has not been reported. To address this gap, we report an enantioselective synthesis of 1,2-disubstituted allylic fluorides using chiral diene-ligated rhodium catalyst, Et₃N ⋅ 3HF as a source of fluoride, and Morita Baylis Hillman (MBH) trichloroacetimidates. Kinetic studies show that one enantiomer of racemic MBH substrate reacts faster than the other. Computational studies reveal that both syn and anti π-allyl complexes are formed upon ionization of allylic substrate, and the syn complexes are slightly energetically favorable. This is in contrast to our previous observation for formation of monosubstituted π-allyl intermediates, in which the syn π-allyl conformation is strongly preferred. In addition, the presence of an electron-withdrawing group at C2 position of racemic MBH substrate renders 1,2-disubstituted π-allyl intermediate formation endergonic and reversible. To compare, formation of monosubstituted π-allyl intermediates was exergonic and irreversible. DFT calculations and kinetic studies support a dynamic kinetic asymmetric transformation process wherein the rate of isomerization of the 1,2-disubstituted π-allylrhodium complexes is faster than that of fluoride addition onto the more reactive intermediate. The 1,2-disubstituted allylic fluorides were obtained in good yields, enantioselectivity, and branched selectivity.     

A Facile Synthesis of 1,1,6-Trimethyl 1,2-Dihydronaphtalene

an easy two-step preparation of 1,1,6-trimethyl 1,2-dihydronaphtalene from α-ionone via 1,1,6-trimethyl 1,2,3,4-tetrahydronaphtalene is described.     

Synthesis and Conformation Analysis of cis-1,2-Disubstituted Cyclododecanes

cis-1,2-Disubstituted cyclododecanes 2 were synthesized by sodium borohydride reduction of 2-monosubstituted cyclododecanones and their structures were confirmed by 1H- NMR, 13C NMR and elemental analysis. The higher cis-selectivity of NaBH4 reduction of 2- monosubstituted cyclododecanones was rationalized by the mode of “corner position carbonyl participation”. Crystal data for 2c: Mr = 263.21, monoclinic, space group P21/c, a = 1.11140(7), b = 2.62590(17), c = 0.91360(6) nm, β = 106.1840(10)°, V = 2.5606(3) nm3, Dc = 1.366 g/cm3, Z = 8, F(000) = 1104, μ(MoKα) = 3.182 mm-1, S = 0.837, the final R = 0.0460 and wR = 0.1033. Crystal X-ray diffraction analysis for 2c showed that its ring skeleton adopts [3333] conformation, in which the OH group presents at the side-exo position and the other one at the corner carbon. The 1H NMR data of 2 showed that 1-corner-R-2-side-exo-OH [3333] and 1-corner-OH-2-side- exo-R [3333] conformations coexist in dynamic equilibrium in the solution, but only the former presents in the crystal.     

Synthesis of 1,2-Disubstituted Ferrocene Containing a Heteroaryl Group

A convenient synthesis of [C₅H₅Fe(1,2-C₅H₃(CH₂R)(Heteroaryl)], (R=NMe₂, Heteroaryl=5-benzoylthien-2-yl(3a), 2-nitropyrid-5-yl(3b), 5-nitrothien-2-yl(3c), 6-methoxy-8-nitroquino-3-yl(3d); R=MeO, Heteroaryl=5-benzoylthien-2-yl(6a), 2-nitropyrid-5-yl)(6b) from [C₅H₅Fe(1,2-C₅H₃(CH₂R)(SnBu₃)], (R=NMe₂, OMe), via Stille coupling reaction is described.     

Facile and Convenient One-pot Synthesis of 1,1-Disubstituted Cyclopropanes in Water

A facile and convenient one-pot synthesis method of substituted cyclopropanes in water has been developed.A series of 1,1-disubstituted cyclopropanes 3 were synthesized from the reaction of β-dicarbonyl compounds 1 with 1,2-dibromoethane 2,in very high yields catalyzed by tetrabutylammonium bromide(TBAB) at 50 oC in the presence of K2CO3 in water.The catalyst TBAB in the aqueous phase can be reused after the separation of organic products.     

A Facile Synthesis of Pyrido [1,2-a] Benzimidazoles

The synthesis and characterisation of some of the new pyrido [1,2-a] benzimidazoles from 1H-benzimidazole-2-acetonitrile and diethyl ethoxy methylene malonic ester.     

Microwave-Promoted Facile and Rapid Synthesis Procedure for the Efficient Synthesis of 5,5-Disubstituted Hydantoins

A fast, general, environmentally friendly, and facile method for preparation of 5, 5-disubstituted hydantoins from the reaction between ketone (or aldehyde) derivatives with KCN and ammonium carbonate under microwave irradiation is presented. The microwaves remarkably accelerated this reaction, the reaction times decreased dramatically, the reaction conditions were milder, and the yields were also greater. Also a comparative study of microwave versus classical conditions has been done. All the products were characterized by infrared, NMR, and CHN analysis, and their melting points are identical to those of the known compounds reported in the literature. This method might be useful in the future for the preparation of similar derivatives.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.]     

The Highly Efficient Synthesis of 1,2-Disubstituted Benzimidazoles Using Microwave Irradiation

The benzimidazole ring of the heterocyclic pharmacophores is one of the most widespread and studied systems in nature. The benzimidazole derivative synthesis study is a crucial point for the development of a clinically available benzimidazole-based drug. Here, we report a simple microwave assisted method for the synthesis of 1,2-disubstituted benzimidazoles. The combination of the molar ratio of N-phenyl-o-phenylenediamine:benzaldehyde (1:1) using microwave irradiation and only 1% mol of Er(OTf)₃ provides an efficient and environmental mild access to a diversity of benzimidazoles under solvent-free conditions. The proposed method allows for the obtainment of the desired products in a short time and with very high selectivity.     

A Facile One-pot Synthesis of 2,5-Disubstituted Oxazoles Using Poly[styrene（iodosodiacetate）]

2,5-Disubstituted oxazoles were prepared conveniently by treatment of aromatic α-methyl ketones and nitriles with poly[styrene(iodosodiacetate)] in a one-pot manner.     

Sodium Perborate: A Facile Synthesis of 1,2-Benzisoxazole 2-Oxides

An efficient and convenient methodology has been developed for the conversion of 2-hydroxy phenyl ketoxime to 1,2-benzisoxazole 2-oxide with sodium perborate (SPB) in glacial acetic acid under mild reaction conditions. Interestingly when the reaction was carried out under reflux condition deoximation was observed in quantitative yield.     

Facile Synthesis of 1,2-Dialkyl-3-Phenyl-4-Quinolinones

The synthesis of 1,2-dialkyl-3-phenyl-4-quinolinones (1) is readily accomplished by a low-temperature reaction of an N-alkylisatoic anhydride with the therraodynamic potassium enolate of phenyl-acetone. The reaction has also been extended to encompass the synthesis of the more complex 2-(3-hydroxy-propyl)-3-(4-fluorophenyl)-1-methyl-4(1H)-quinolinone (10).     

Facile Synthesis of 1,2-bis-(Cyanomethyl)Benzenes

3-Alkoxy-1,2-bis-(cyanomethyl)benzenes can be prepared in two steps, in high yield, from m-alkoxy-N.N-dimethylbenzylamines by directed metallation followed by ethyl chloroformate-promoted cyanide displacement.     

Stereoselective Synthesis of Steroidal Aziridines

A number of papers related to synthesis of steroidal aziridines have been published^1–5. We wish to report here in a simple method with excellent yield for the stereoselective synthesis of steroidal aziridines.     

A Facile Synthesis of 1,2-Anhydro-6-O-acetyl-3,4-di-O-benzyl-d-glycopyranoses and 1,2-Anhydro-5-O-acetyl-3-O-benzyl-D-glycofuranoses

The ability to couple carbohydrate entities to produce glycosides or higher oligomers is an important goal of synthetic organic chemistry.¹ For the past several decades, methods to construct glycosidic linkages have improved as a result of the development of glycosidation procedures.² However, owing to their structural complexity, synthesis of oligosaccharides is still a laborious task compared with the synthesis of oligopeptides and oligonucleotides. Many additional sugar derivatives which can improve and simplifjr synthetic procedures of oligosaccharides are needed.     

二氟甲基取代氮杂环丙烷的不对称合成

以(S)-叔丁基亚磺酰胺和二氟取代酮为原料制得8个二氟甲基取代的叔丁基亚磺酰亚胺(2a~2h);2a~2h与硫叶立德经不对称加成反应合成了12个二氟甲基取代的叔丁基亚磺酰基氮杂环丙烷(3a~3h),其结构经1H NMR,13C NMR,19F NMR,FT-IR和HR-ESI-MS确证。     

A Novel Approach to 2,2-Disubstituted 1,2-Dihydro-4-phenylquinolines

The reaction of 2-(1-phenylvinyl)aniline and 4-chloro-2-(1-phenylvinyl)aniline with acetophenone derivatives, 1-(naphthalen-1-yl)ethanone and 1-(furan-2-yl)ethanone in toluene at 110–115° with toluene-4-sulfonic acid as a catalyst leads in good-to-excellent yields to the 2,2-disubstituted 1,2-dihydro-4-phenyl-quinolines 1–18 (Scheme 1, Table). The structure of the new racemic 1,2-dihydroquinolines 1–18 is determined by NMR spectroscopy. A reaction mechanism proceeding via a 6π-electrocyclic rearrangement of 2-(1-phenylvinyl)anils 19 as the key step is proposed for the formation of these compounds (Scheme 1). The scope and limitations of the novel methods are discussed (Scheme 2).