金属参与的N-酰基腙的偕二氟烯丙基化反应：高效合成偕二氟高烯丙基胺

金属铟参与醛衍生的N-酰基腙 1a-1q,4a-4g与3-溴-3,3-二氟丙烯 2 的反应,分别高效得到α, α-二氟高烯丙基肼 3a-3q,5a-5g。该反应条件温和,操作简便。硝基,酚羟基,苄氧基,α, β-不饱和醛的碳-碳双键等官能团对该反应具有良好的官能团兼容性。通过用锌粉代替铟粉, 酮衍生的N-酰基腙 6a-6d 也能发生偕二氟烯丙基化反应,以中等产率得到α, α-二氟高烯丙基肼 7a-7d。裂解肼3a的 N-N键顺利得到偕二氟高烯丙基胺 8,化合物 8 经丙烯酰化,随后进行RCM关环反应,可以方便的转化为偕二氟-γ-取代α, β-不饱和内酰胺 11。     

‘Click Synthesis’ of Some Novel Benzimidazol Oxime Ethers Containing Heterocycle Residues as Potential ß‐Adrenergic Blocking Agents

The ‘click synthesis’ of some novel O‐substituted oximes, 5a – 5j , which contain heterocycle residues, as new analogs of ß‐adrenoceptor antagonists is described (Scheme 1). The synthesis of these compounds was achieved in four steps. The formation of (E)‐2‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylethanone oxime, followed by their reaction with 2‐(chloromethyl)oxirane, afforded mixture of oil compounds 3 and 4 , which by a subsequent tetra‐n‐butylammonium bromide (TBAB)‐catalyzed reaction with N H heterocycle compounds (Scheme 1), led to the target compounds 5a – 5j in good yields.     

Trimethylsilyl derivatives of aliphatic nitro compounds in α,β-C,C-cross-coupling

A new α,β-C,C-cross-coupling reaction of derivatives of aliphatic nitro compounds, silyl nitronates andN,N-bis(silyloxy)enamines, leading to β-nitro oximes was found. The scope and limitations of this reaction were studied, and a mechanism was proposed.     

Oligonucleosides with a Nucleobase‐Including Backbone,Part 3, Synthesis of Acetyleno‐Linked Adenosine Dimers

The adenosine‐derived dimers 14a – d and 15b – d have been prepared by coupling the protected 8‐iodoadenosines 3 and 13 with the C(5′)‐ethynylated adenosine derivatives 5 , 6 , 11 , and 12 (Scheme 4). Similarly, the 5′‐epimeric dimer 16 was prepared by coupling 3 with the alkyne 8 (Scheme 5). The propargylic alcohol 4 was transformed into the N‐benzoylated alkyne 5 and into the amine 6 , while the epimeric alcohol 7 was converted to the epimeric amine 8 and the 5′‐deoxy analogues 11 and 12 (Scheme 3). Cross‐coupling of the iodoadenosine 13 with the alkyne 5 to 14a was optimised; it is influenced by the N‐benzoyl and the Et₃SiO group of the alkyne, but hardly by the N‐benzoyl group of the 8‐iodoadenosine. The alkyne is most reactive when it is O‐silylated, but not N‐benzoylated. Cross‐coupling of the 5′‐deoxyalkynes proceeded more slowly. The dimers 14a – d , 15b – d , and 16 were obtained in good yields (Table 2). Deprotection of 14d and 16 led to 18 and 20 , respectively (Scheme 5). The diols 17 and 19 and the hexols 18 and 20 prefer the syn‐conformation in (D₆)DMSO, completely for unit II and ≥80% for unit I; they exhibit partially persistent intramolecular O(5′)−H⋅⋅⋅N(3) H‐bonds. The persistence increases from 18% (unit I of 19 ), 32% (unit II of 17 and 19 ), 45% (unit I of 17 ), 52% (unit II of 18 and 20 ), and 55% (unit I of 20 ) to 82% (unit I of 18 ).     

Quenching of Singlet Oxygen by Tertiary Aliphatic Amines. Structural Effects on Rates and Products

A kinetic and product study of the reaction of a series of α‐methyl‐substituted N‐methylpiperidines with thermally generated ¹O₂ in MeCN was carried out. It was found that as the number of α‐methyl groups (Me in α‐position relative to the N‐atom) increases, the rate of ¹O₂ quenching (physical plus chemical) slightly decreases. This finding shows that, with respect to the reaction rate, steric effects are much more important than electronic effects as the latter should have produced the opposite result. The opposite outcome was instead found for the chemical quenching that leads to the N‐demethylation products and N‐formyl derivatives. The same trend was observed for the ratio between N‐demethylation and formation of the N‐formyl derivatives (NH/NCHO ratio). All these results are consistent with the mechanism reported in Scheme 1 where an exciplex is first formed that by a H‐atom transfer process produces an α‐amino‐substituted C‐radical. The latter forms the product of N‐demethylation by one electron oxidation, or affords the N‐formyl derivative by radical coupling (Scheme 1). Similar results were obtained with N,N‐dimethylcyclohexanamine. However, this ‘acyclic’ amine exhibited behaviors quite distinct from those of the N‐methylpiperidines series, with respect to reaction rate, extent of chemical quenching, and NH/NCHO ratio.     

‘Click Synthesis’ of Some Novel O‐Substituted Oximes Containing 1,2,3‐Triazole‐1,4‐diyl Residues as New Analogs of β‐Adrenoceptor Antagonists

The ‘click synthesis’ of some novel O‐substituted oximes, 7a – 7t , which contain 1,2,3‐triazolediyl residues, as new analogs of β‐adrenoceptor antagonists is described (Schemes 1–4). The synthesis of these compounds was achieved in four to five steps. The formation of oximes of 9H‐fluoren‐9‐one and benzophenone, i.e., 9a and 9b , respectively, followed by their reaction with propargyl bromide, afforded O‐propargyl oximes 10a and 10b , respectively, which by a subsequent CuI‐catalyzed Huisgen cycloaddition with prepared β‐azido alcohols 11a – 11j (Schemes 2 and 3), led to the target compounds 7a – 7t in good yields.     

Design and Synthesis of Some Novel Oxiconazole‐Like Carboacyclic Nucleoside Analogues,as Potential Chemotherapeutic Agents

The syntheses of some novel carboacyclic nucleosides, 17a – 17o , containing oxiconazole‐like scaffolds, are described (Schemes 1–3). In this series of carboacyclic nucleosides, pyrimidine as well as purine and other imidazole derivatives were employed as an imidazole successor in oxiconazole. These compounds could be prepared in good yields by using two different strategies (Schemes 1 and 2). Due to Scheme 1, the N‐coupling of nucleobases with 2‐bromoacetophenones was attained for 18a – 18e , and their subsequent oximation affording 19a – 19e and finally O‐alkylation with diverse alkylating sources resulted in the products 17a – 17g, 17n , and 17o . In Scheme 2, use of 2‐bromoacetophenone oximes 20 , followed by N‐coupling of nucleobases, provided 19f – 19j whose final O‐alkylation produced 17h – 17m (Scheme 2). For the rational interpretation of the dominant formation of (E)‐oxime ethers rather than (Z)‐oxime isomers, PM3 semiempirical quantum‐mechanic calculations were discussed and the calculations indicated a lower heat of formation for (E)‐isomers.     

Stereoselective approach to conjugated enone oximes from aliphatic nitro compounds and sulfur ylides

A novel approach to conjugated enone oximes from aliphatic nitro compounds deals with double silylation of N,N-bis(silyloxy) enamines followed by a stereoselective reaction with an ester-stabilized sulfur ylide. The proposed mechanism involves the generation of labile nitrosoalkenes as intermediates, which react with the sulfur ylide to give target enone oximes.     

Substituted Tetraaza‐ and Hexaazahexacenes and their N,N′‐Dihydro Derivatives: Syntheses,Properties, and Structures

The palladium‐catalyzed coupling of a substituted o‐diaminoanthracene and a substituted o‐diaminophenazine to substituted 2,3‐dichloroquinoxalines furnishes 10 differently substituted N,N′‐dihydrotetraaza‐ or ‐hexaazahexacenes with the quinoxaline group of the azaacenes carrying fluorine, chlorine, or nitro groups. The N,N′‐dihydrotetraazahexacenes with hydrogen, chlorine, and fluorine subtituents are oxidized to azaacenes, whereas only the parent N,N′‐dihydrohexaazahexacenes, with hydrogen substituents, are oxidized by MnO₂. The resultant azaacenes are characterized by their optical and spectroscopic data. In addition, single‐crystal X‐ray structures have been obtained for the parent tetraazahexacenes and their difluoro‐substituted derivatives. The di‐ and tetrachloro derivatives of the N,N′‐dihydrohexaazahexacene have also been structurally characterized.     

Indolyl Linked Meta‐Substituted Benzylidenes as Novel Ligands: Synthesis,Biological Evaluation,and Molecular Docking Studies

Synthesis of indolyl linked benzylidene based meta‐substituted phenyl containing thiazolidinediones ( 4a – b ), rhodanine ( 5a – b ), and 1,3‐dicarbonyl based acyclic analogs of isoxazolidinediones ( 6a – 7b ) in an effort to develop novel α‐glucosidase inhibitors in the management of hyperglycemia for the treatment of type 2 diabetes is reported. The structure of all the novel synthesized compounds was confirmed through the spectral studies (LC–MS, ¹H‐NMR, ¹³C‐NMR, and FTIR). Comparative evaluation of these compounds revealed that the compound 5b showed maximum inhibitory potential against α‐amylase and α‐glucosidase giving an IC₅₀ value of 0.28 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 5b was considered as promising candidate of this series.     

Synthesis and Antimicrobial Activity of Azolyl Pyrimidines

A new class of azolyl pyrimidines linked by diamino sulfone moiety was prepared and studied their antimicrobial activity. Chloro‐substituted and nitro‐substituted thiazolyl pyrimidines ( 9c and 9e ) showed excellent antibacterial activity against Bacillus subtilis , while imidazolyl pyrimidines ( 10c and 10e ) exhibited promising antifungal activity against Aspergillus niger .     

Polar aspects of intramolecular interactions in 2‐amino‐5‐nitro‐4‐methylpyridines and 2‐amino‐3‐nitro‐4‐methylpyridines

The dipole moments of twelve 2‐N‐substituted amino‐5‐nitro‐4‐methylpyridines ( I‐XII ) and three 2‐N‐substituted amino‐3‐nitro‐4‐methylpyridines ( XIII‐XV ) were determined in benzene. The polar aspects of intramolecular charge‐transfer and intramolecular hydrogen bonding were discussed. The interaction dipole moments, μ_int, were calculated for 2‐N‐alkyl(or aryl)amino‐5‐nitro‐4‐methylpyridines. Increased alkylation of amino nitrogen brought about an intensified push‐pull interaction between the amino and nitro groups. The solvent effects on the dipole moments of 2‐N‐methylamino‐5‐nitro‐4‐methyl‐( I ), 2‐N,N‐dimethylamino‐5‐nitro‐4‐methyl‐ ( II ) and 2‐N‐methylamino‐3‐nitro‐4‐methylpyridines ( XIII ) were different. Specific hydrogen bond solute‐solvent interactions increased the charge‐transfer effect in I , but it did not disrupt the intramolecular hydrogen bond in XIII.     

(n‐Nitrophenyl)acetonitrile,with n = 2, 3 and 4

The molecular structures of the three title nitro‐substituted phenyl­aceto­nitriles, C₈H₆N₂O₂, at 123 K show that the mol­ecules are linked together very differently. In the 2‐ and 4‐nitro compounds, there are both O?H and N_cyano?H interactions, whereas the crystal lattice of the 3‐nitro compound is essentially built up by O?H interactions. The O atoms seem to prefer the aromatic H atoms, while the cyano N atoms prefer the methyl­ene H atoms. The phenyl–nitro torsion angles are ?19.83 (13), ?5.69 (12) and ?2.88 (12)°, while the phenyl–cyano­methyl torsion angles are ?62.27 (12), ?147.99 (9) and ?16.75 (14)° in the 2‐, 3‐ and 4‐NO₂‐substituted compounds, respectively.     

Copper‐Catalyzed Cascade Cyclization Reaction of 2‐Haloaryltriazenes and Sodium Azide: Selective Synthesis of 2 H‐Benzotriazoles in Water

A new approach to the synthesis of 2 H‐benzotriazoles is described. This strategy is based on the copper‐catalyzed C?N coupling of 2‐haloaryltriazenes or 2‐haloazo compounds with sodium azide and the intramolecular addition of nitrene to N?N bonds. This approach allows the synthesis of various N‐amino‐ and N‐aryl‐2 H‐benzotriazoles in water, in good to excellent yields. The procedure is simple and the starting materials and catalyst are easily available, offering a practical and convenient synthetic route to 2‐substituted benzotriazoles.     

Synthesis of Nonsymmetrically N,N′‐Diaryl‐Substituted 4,4′‐Bipyridinium Salts with Redox‐Tunable and Titanium Dioxide (TiO2)‐Anchoring Properties

A general method for the synthesis of so far unknown nonsymmetrically substituted N‐aryl‐N′‐aryl′‐4,4′‐bipyridinium salts is presented (Scheme 1). The common intermediate in all procedures is N‐(2,4‐dinitrophenyl)‐4,4′‐bipyridinium hexafluorophosphate ( 1 ⋅ ). For the synthesis of nonsymmetric arylviologens, 1 ⋅ was arenamine‐exchanged by the Zincke reaction, and then activated at the second bipyridine N‐atom with 2,4‐dinitrophenyl 4‐methylbenzenesulfonate. The detailed preparation of the six N‐aryl‐N′‐aryl′‐viologens 21 – 26 is discussed (Scheme 2). The generality of the procedure is further exemplified by the synthesis of two nonsymmetrically substituted N‐aryl‐N′‐benzyl‐ (see 11 and 12 ), and seven N‐aryl‐N′‐alkyl‐4,4′‐bipyridinium salts (see 28 – 34 ) including substituents with metal oxide anchoring and redox tuning properties. The need for these compounds and their usage as electrochromic materials, in dendrimer synthesis, in molecular electronics, and in tunable‐redox mediators is briefly discussed. The latter adjustable property is demonstrated by the reduction potential measured by cyclic voltammetry on selected compounds (Table).     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

A Simple,Convenient, and Efficient Synthetic Route for The Preparation of (Z)‐3,5‐Dichloro‐N‐(3‐(4‐substitutedphenyl)‐4‐phenylthiazole‐2(3H)‐ylide)benzamide Heterocyclic Compounds from Aroyl Thiourea Derivatives via S‐cyclization Mechanism

A series of variously substituted 1,3‐thiazole heterocyclic compounds ( 3a – 3d ) were prepared by base‐catalyzed S‐cyclization of corresponding 2,4‐dichloro‐N‐{[(4‐substitutedphenyl)amino]carbonothioyl}benzamide ( 2a – 2d ) with acetophenone in the presence of bromine. The structure of all compounds was established by IR, ¹H‐NMR, ¹³C‐NMR, elemental analysis, and X‐ray crystallographic analysis.     

Synthesis,antimicrobial activity,and molecular docking study of formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamides

In the present study, substituted formylnaphthalenyloxymethyl‐triazolyl‐N‐phenylacetamide derivatives ( 6a – k ) have been designed and synthesized employing click chemistry approach and evaluated for their in vitro antifungal and antibacterial activities. All the newly synthesized compounds were thoroughly characterized by ¹H NMR, ¹³C NMR, and HRMS spectral techniques. Among the screened compounds, 6d , 6e , 6j , and 6k have shown good antifungal and antibacterial activities. Compound 6k has shown very effective antimicrobial activity. We further performed exploratory docking studies on microbial DNA gyrase to rationalize the in vitro biological data and to demonstrate the mechanism of antimicrobial activity. This is the first report to demonstrate the formylnaphthalenyloxymethyl, triazole, and N‐phenylacetamide hybrids as potential antimicrobial agents.     

Copper‐Catalyzed Decarboxylative Radical Silylation of Redox‐Active Aliphatic Carboxylic Acid Derivatives

A decarboxylative silylation of aliphatic N ‐hydroxyphthalimide (NHPI) esters using Si−B reagents as silicon pronucleophiles is reported. This C(sp³)−Si cross‐coupling is catalyzed by copper(I) and follows a radical mechanism, even with exclusion of light. Both primary and secondary alkyl groups couple effectively, whereas tertiary alkyl groups are probably too sterically hindered. The functional‐group tolerance is generally excellent, and α‐heteroatom‐substituted substrates also participate well. This enables, for example, the synthesis of α‐silylated amines starting from NHPI esters derived from α‐amino acids. The new method extends the still limited number of C(sp³)−Si cross‐couplings of unactivated alkyl electrophiles.     

Photochemistry of N‐(2‐Acylphenyl)‐2‐methylprop‐2‐enamides: Competition between Photocyclization and Long‐Range Hydrogen Abstraction

The photochemical reactions of various ‘N‐methacryloyl acylanilides’ (=N‐(acylphenyl)‐2‐methylprop‐2‐enamides) have been investigated. Under irradiation, the acyl‐substituted anilides 1a – 1c and 1o afforded exclusively the corresponding quinoline‐based cyclization products of type 2 (Table 1). In contrast, irradiation of the benzoyl (Bz)‐substituted anilides 1e – 1h afforded a mixture of the open‐chain amides 4e – 4h and the cyclization products 2e – 2h . Irradiation of the para‐acyl‐substituted anilides 6a – 6e and 6h afforded the corresponding quinoline‐based cyclization products of type 5 as the sole products (Table 2). The formation of the cyclization products 2a – 2c and 2o can be rationalized in terms of 6π‐electron cyclization, followed by thermal [1,5] acyl migration, and that of compounds 3p, 5a – 5e , and 5h can be explained by a 6π‐electron cyclization only. The formation of the open‐chain amides 4e – 4h probably follows a mechanism involving a 1,7‐diradical, C and a spirolactam of type D (Scheme). Long‐range ζ‐H abstraction by the excited carbonyl O‐atom of the benzoyl group on the aniline ring is expected to proceed via a nine‐membered cyclic transition state, as proposed on the basis of X‐ray crystallographic analyses (Fig. 2).