Palladium-Catalyzed Domino Reaction for the Synthesis of 3-Amino 1,2,4-Benzothiadiazine 1,1-Dioxides

A palladium-catalyzed domino reaction of 2-azidosulfonamides and isocyanides enables the synthesis of 3-amino-substituted 1,2,4-benzothiadiazine 1,1-dioxides at room temperature. By applying commercially available Pd(dba)₂ in catalyst loadings as low as 1.0 mol%, a variety of 21 differently substituted 2H-1,2,4-benzothiadiazine 1,1-dioxides can be prepared within 2 h. Moreover, the developed protocol gives access to the related 4H heterocycles.     

Isothiazol-1,1-dioxide – vom Süßstoff zum chiralen Auxiliar in der stereoselektiven Synthese

Isothiazole 1,1-dioxides – From Sweeter to Chiral Auxiliar in the Stereoselective Synthesis This review gives a report of the last ten years on the new synthetic methods, reactions and biological applications of isothiazole 1,1-dioxide derivatives. the formation of monocyclic and heterocyclic annelated isothiazole 1,1-dioxides by oxidation of isothiazoles, cyclocondensation of sulfonamides and cycloaddition of isothiazol-3(2H)-one 1,1-dioxides are discussed in more detail. Furthermore, the preparation of pharmacologically important N-substituted saccharines is reported. New saccharine-derived chiral N-enoyl-and N-acyl-2,3-dihydro-1,2-benzisothiazole 1,1-dioxides serve as advantageous stereoface-directing dienophile and dipolarophile auxiliaries in Diels-Alder-reactions and 1,3-dipolar cycloadditions. Asymmetric alkylations, acylations and aldolizations are also described.     

Oxidation of Acceptor‐substituted Isothiazolium‐2‐imines to Stable Cyclic Sulfin‐ and Sulfonamides with 3‐Hydroperoxy Function

The oxidation of isothiazolium 2‐imines 3,5 and their salts 4 to stable 3‐hydroperoxy‐2,3,4,5,6,7‐hexahydro‐1,2‐benzisothiazole 1‐oxides 7 and 1,1‐dioxides 8 and 9 as a new class of cyclic sultims and sultams is described. The formation of 3‐hydroxysultams 10 and isothiazol‐3(2H)one 1,1‐dioxides 11 is presented.     

Synthesis of α‐Carbolines Starting from 2,3‐Dichloropyridines and Substituted Anilines

9H‐α‐Carbolines have been prepared via consecutive intermolecular Buchwald–Hartwig reaction and Pd‐catalyzed intramolecular direct arylation from commercially available 2,3‐dichloropyridines and substituted anilines. The combination of a high reaction temperature (180 °C) and the use of DBU were found to be crucial for the intramolecular direct arylation reactions of the 3‐chloro‐N‐phenylpyridin‐2‐amines as no reaction was observed at 120 °C and 180 °C using different inorganic and other organic bases. On the other hand, nitrogen‐methylated pyridine analogues of these substrates {N‐[3‐chloro‐1‐methylpyridin‐2(1H)‐ylidene]anilines} do undergo ring closure at 120 °C, with K₃PO₄ as base, affording the respective 1‐methyl‐1H‐α‐carbolines in good yields.     

Some reactions of 1,3-Dichloro-2-azoniaallene Salts with heteronucleophiles

1,3-Dichloro-2-azoniaallene hexachloroantimonates ( 1 ) reacted with H₂S to give 1,2,4-dithiazolium salts 2 . With hydrazines 1,2,4-triazolium salts ( 3, 4 ) were formed. 1,3-Dimethylurea, respectively 1,3-dimethylthiourea or ethyl allophanate, reacted with 1 to afford 2-oxo- or 2-thioxo-1,3,5-triazinium salts ( 5–7 ). With diphenylmethaneimines imino substituted 2-azoniaallene salts 8 were produced. From chloroacetonitrile dichloropyrimidines 9 , and from the tricyanomethyl anion a hexatriene 10 and a triazine 11 could be prepared. The 1,5-dichloro substituted 2-azoniaallene salts 12 reacted as bifunctional electrophiles with nucleophiles such as benzophenone hydrazone or anilines, to furnish 1,3,5-triazinium salts 14 . Against benzohydrazide the allene 12j behaved as trivalent electrophile giving the bicyclic 1,3,5-oxadiazinium salt 13j , the constitution of which has been secured by a crystal structural analysis. The vinyl-2-azoniaallene salt 1i cyclized on heating to the 1,3-thiazinium salts 16, 17 . From 17 the triazinium salts 18 were prepared with alcohols.     

An Expeditious Copper‐Catalyzed Access to 3‐Aminoquinolinones, 3‐Aminocoumarins and Anilines using Sodium Azide

An efficient copper‐catalyzed in situ C(sp²) NH₂ bond formation to provide a range of 3‐aminoquinolin‐2(1H)‐ones and 3‐aminocoumarins from 3‐bromoquinolinones and 3‐bromocoumarins, respectively, has been achieved. The reaction conditions involve the use of copper powder as the catalyst, eco‐friendly ethanol as the solvent in the presence of pipecolinic acid as the ligand and ascorbic acid as the additive. The efficiency of this practical method was demonstrated in the synthesis of various anilines.     

Base-induced reactions of isothiazolium salts with active 5-methyl or 5-methylene groups

It is shown that N-phenyl-substituted isothiazolium salts 2/3a–e with active 5-methyl or 5-methylene groups can easily be obtained by reaction of β-thiocyanatovinylaldehydes 1 and substituted anilines. Based on a wide variety of isothiazolium salts accessible in that way, a study of their various reaction products, e.g. 1,6-diphenyl-substituted thiadiazapentalenes 4a–d , 5a–j and special spiro compounds 6 , and the influence of donor and acceptor substituents becomes possible. The structure of the basic skeleton of the thiadiazapentalenes was confirmed by X-ray analysis and ab initio MO calculations. Some mechanistic aspects are supported by the MO results.     

Structural and Preliminary Explosive Property Characterizations of New 3,4,5‐Triamino‐1,2,4‐triazolium (Guanazinium) Salts

Two new highly stable energetic salts were synthesized in reasonable yield by using the high nitrogen‐content heterocycle 3,4,5‐triamino‐1,2,4‐triazole and resulting in its picrate and azotetrazolate salts. 3,4,5‐Triamino‐1,2,4‐triazolium picrate (1) and bis(3,4,5‐triamino‐1,2,4‐triazolium) 5,5′‐azotetrazolate (2) were characterized analytically and spectroscopically. X‐ray diffraction studies revealed that protonation takes place on the nitrogen N1 (crystallographically labelled as N2). The sensitivity of the compounds to shock and friction was also determined by standard BAM tests revealing a low sensitivity for both. B3LYP/6–31G(d, p) density functional (DFT) calculations were carried out to determine the enthalpy of combustion (Δ_cH (1) =−3737.8 kJ mol⁻¹, Δ_cH (2) =−4577.8 kJ mol⁻¹) and the standard enthalpy of formation (Δ_fH° (1) =−498.3 kJ mol⁻¹, (Δ_fH° (2) =+524.2 kJ mol⁻¹). The detonation pressures (P (1) =189×10⁸ Pa, P (2) =199×10⁸ Pa) and detonation velocities (D (1) =7015 m s⁻¹, D (2) =7683 m s⁻¹) were calculated using the program EXPLO5.     

End-functionalized polymers by living cationic polymerization

Summary End-functionalized poly(isobutyl vinyl ether) (2) with a terminal amine, carboxylic acid, or ester group was prepared by quenching the HI/I₂-initiated living polymer ends with ring-substituted anilines (H₂N-C₆H₄-X, p or m; X = NH₂, COOH, COOC₂H₅). The living polymerization of isobutyl vinyl ether and the subsequent end-capping reaction were carried out at –15°C in methylene chloride. The resulting polymers exhibited a narrow molecular weight distribution and carried one terminal function (aniline residue) per chain, according to ¹H NMR structural analysis.     

The synthesis of some phthalocyanines derived from bulky substituted phthalonitriles

Phthalocyanine precursors were prepared by displacement of the –CH proton in 1-chloro-3,4-dicyano-6-(1,1-dicarbethoxymethyl) benzene with 1-(chloromethyl)-2-methyl benzene and 1-(chloromethyl)-4-methyl benzene. Metallo-phthalocyanines were obtained by cyclotetramerization in the presence of template metal salts {Zn(CH₃COO)₂, CoCl₂, CuCl₂, and Pb(CH₃COO)₂·3H₂O} that possessed substituents to enhance the solubility of the macrocycle and reduce its propensity to aggregate in solution. The structures of the newly synthesized molecules were proposed according to elemental analysis and ¹H NMR, FT-IR, Micro-TOF mass, MALDI-TOF mass and UV–vis spectral data.     

Novel Brønsted acidic ionic liquids catalyzed one-pot reaction of highly green regioselective thiocyanation of N-containing aromatic and heteroaromatic compounds at room temperature

In this method, a novel Brønsted acidic ionic liquid silica-supported pyridinium sulfonic acid thiocyanate {SiO₂@[Pyridine-SO₃H]SCN} and sulfonic acid-functionalized pyridinium chloride {[PSA]Cl} were easily synthesized and characterized. In the first method, {SiO₂@[Pyridine-SO₃H]SCN as a novel and environmentally friendly catalyst with one acidic functional group and one thiocyanation agent group was ef?ciently used for the synthesis of aryl and heteroaryl thiocyanates via the condensation of anilines, indoles, pyrroles, and their derivatives in the presence of H₂O₂ as a green oxidant in EtOH:H₂O (1:1) at room temperature. In the second method, {[PSA]Cl} as a new ionic liquid and environmentally friendly catalyst with one acidic functional group was used for the simple and efficient synthesis of aryl and heteroaryl thiocyanates via the condensation of anilines, indoles, pyrroles, and their derivatives with NH₄SCN in the presence of H₂O₂ as a green oxidant in EtOH:H₂O (1:1) at room temperature. A simple experimental procedure, clean reaction profile, use of an inexpensive catalyst, and recyclability of the catalyst are some of the advantages of the procedure. Also, one of the advantages of the first method is the non-usage of NH₄SCN or KSCN in the reaction.     

Hydrogen pressure-dependence in the ring-opening reactions of substituted cyclopropanes over Rh/SiO2 catalyst

The hydrogen coverage and the structures of the reactants influence the selectivity and mechanism of the ring-opening reactions of ethyl-(ECP),cis-1,2-dimethyl-(cDMCP),trans1,2-dimethyl-(tDMCP), 1,1-dimethyl-(1, 1DMCP) and 1, 1, 2, 2-tetramethylcyclopropane (TMCP) over Rh/SiO₂ catalyst; a new phenomenon was observed for the transformations of ECP,tDMCP and 1, 1DMCP, viz. the turnover frequency vs. H₂ pressure functions pass through a minimum.     

Dipeptides from methionine and S-methylcysteine as chiral ligands for asymmetric Michael reactions

Dipeptides derived from methionine and S-methylcysteine 3a – d have been prepared and screened as chiral ligands in combination with 13 metal salts 4a – m towards the catalysis of an asymmetric Michael reaction of a β-keto ester 1 with methyl vinyl ketone 2 resulting in an optimal ee of 18% achieved with FeCl₃ · 6 H₂O 4c as the metal salt.     

4-(1-Methyl-2-sulfamoylvinyl)pyrazoles by Ring Transformation of 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes with hydrazines

As masked 1,3-dicarbonyl compounds, 1,1-dioxo-2H-1,2-thiazine-4-carbaldehydes ( 2a–e, 7 ) undergo ring transformations with nucleophilic hydrazines to produce 4-[1-methyl-2-(arylsulfamoyl)vinyl]pyrazoles ( 9a–i ). For 9h , an X-ray structural analysis is reported. With less nucleophilic semicarbazide and p-nitrophenylhydrazine the hydrazones ( 11a, b ) were isolated. The carbaldehydes 2a–e , 7 and 8a, b were synthesized by formylation of the 1,1-dioxo-2H-1,2-thiazines 1a–e, 5 and 6a, b with dichloromethyl methyl ether/TiCl₄. In the case of 1a–e mixtures of 4- and 6-carbaldehydes ( 2a–e/3a–e ) were obtained, which, however, could be used for the synthesis of pyrazoles.     

Selective Complexation and Membrane Transport of Guanidinium Salts by Calix[6]arene Amides

The p-tert-butylcalix[6]arene hexamide 2 and syn-1,3,5–trimethoxy-2,4,6-triamide 4 were synthesized by reaction of α-chloro-N,N-diethylacetamide and the corresponding calix[6]arenes 1 and 3 , respectively. ¹H NMR spectroscopy shows that 2 is a mixture of different conformations whereas 4 is fixed in a cone conformation. Extraction experiments, (S-L) and (H₂O–CDCl₃) with picrate salts, indicate that 2 complexes both alkali metal (1:2 complex) and guanidinium salts (1:1 complex) but 4 complexes only guanidinium (1:1 complex). Incorporated in supported liquid membranes (Accurel^® / o-nitrophenyl n-octyl ether) the calixarenes 2 and 4 transport guanidinium salts. The hexamide 2 is a more efficient carrier of guanidinium but the syn-1,3,5-trimethoxy-2,4,6-triamide 4 is much more selective. Both 2 and 4 are sufficiently lipophilic to give membranes that are stable over longer periods (weeks).     

Response of Two-Dimensional Polymeric Cadmium Ferrocenyl Disulfonates to Heavy Metal Ions

A sandwich-like 2D infinite framework of {[Cd(pbbm)₂(SO₃FcSO₃)]·(CH₃OH)₂·(H₂O)₆} _n (1) with nanosized porous structure [Fc(SO₃)₂Na₂ = ferrocene-1,1′-disulphonate, pbbm = 1,1′-(1,3-propylene)-bis-1H-benzimidazole] was prepared by combining d ¹⁰ Cd²⁺ ions with highly conjugated pbbm and disodium ferrocene-1,1′-disulfonate. Experimental results show that 1 could serve as a new fluorescent probe for the detection of many divalent metal ions in water, such as Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Ag⁺, Cd²⁺, Hg²⁺ and Pb²⁺, and trace organic solvents, including acetone, toluene, methylene chloride, ether, tetrahydrofuran, and methanol. The main product was very different from previous chemosensory materials that only identify one or two metal ions. The powdery multipurpose chemosensory materials proposed here could also sequester dangerous heavy metal ions, especially Pb²⁺. A computational study of ferrocene-1,1′-disulfonate and 1 gave insight into the process of ion exchange and sorption. This study introduces a promising new field of fluorescent chemosensors based on nanoporous coordination polymers with free functional groups.     

Palladium‐Catalyzed Benzylic C?H Benzylation via Bis‐Benzylpalladium(II) Complexes in Water: An Effective Pathway for the Direct Construction of N‐(1,2‐Diphenylethyl)anilines

A strategy for the N‐benzylation/benzylic C H benzylation cascade of anilines by the π‐benzylpalladium system using a water‐soluble palladium(0)/sodium diphenylphosphinobenzene‐3‐sulfonate (TPPMS) catalyst and benzyl alcohol in water has been developed. This tandem process is devised as a novel and efficient synthetic route for N‐(1,2‐diphenylethyl)anilines. Benzylic C H activation of a mono‐N‐benzylated intermediate with a π‐benzylpalladium(II) complex affords a bis‐π‐benzylated palladium(II) intermediate. The nucleophilic η¹‐σ‐benzyl anion ligand attacks the electrophilic η³‐π‐benzyl ligand to give a dibenzylated product. The intermolecular competition between mono‐N‐benzylaniline and its monodeuterated form (monodeuterated at the benzylic group) with benzyl alcohol gave a KIE=4.6, suggesting that C H bond cleavage was involved in the rate‐determining step. Hammett studies on the rate constants of benzylation by various substituted anthranilic acids and mono‐N‐benzylanilines show a good correlation between the log(k_X/k_H) and the σ values of the respective substituents. From the slope, negative ρ values are obtained, suggesting that there is a build‐up of positive charge in the transition state. The reaction of anilines with electron‐donating and electron‐withdrawing groups affords the corresponding N‐(1,2‐diphenylethyl)anilines in moderate to good yields (54–86%). Interestingly, the reaction of anthranilic acids proceeded smoothly to give only the corresponding dibenzylated products in good to excellent yields (70–87%). The carboxyl group of the anthranilic acids acts as a directing group in the benzylic C H activation process.

     

A Hofmann Rearrangement–Ring Expansion Cascade for the Synthesis of 1‐Pyrrolines: Application to the Synthesis of 2,3‐Dihydro‐1H‐pyrrolo[2,1‐a]isoquinolinium Salts

Treatment of cyclobutanecarboxamide with bis(trifluoroacetoxy)iodobenzene, PhI(OCOCF₃)₂, resulted in the formation of 1‐pyrroline via Hofmann rearrangement of the former followed by in situ ring expansion reaction of the cyclobutylamine intermediate. Further elaboration of this methodology to the synthesis of 2,3‐dihydro‐1H‐pyrrolo[2,1‐a]isoquinolinium salts has also been described.

     

2,2′-Bipyridine-Modified Tamoxifen: A Versatile Vector for Molybdacarboranes

Investigations on the antitumor activity of metallacarboranes are sparse in the literature and limited to a handful of ruthena- and molybdacarboranes. In this study, the molybdacarborane fragment [3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] was combined with a vector molecule, inspired by the well-known drug tamoxifen or 4,4′-dihydroxytamoxifen (TAM-diOH). The molybdacarborane derivative [3,3-{4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine-κ²N,N′}-3-(CO)₂-closo-3,1,2-MoC₂B₉H₁₁] ( 10 ), as well as the ligand itself 4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2′-bipyridine ( 6 ) showed cytotoxic activities in the low micromolar range against breast adenocarcinoma (MDA-MB-231, MDA-MB-361 and MCF-7), human glioblastoma (LN-229) and human glioma (U-251) cell lines. In addition, compounds 6 and 10 were found to induce senescence and cytodestructive autophagy, lower ROS/RNS levels, but only the molybdacarborane 10 induced a strong increase of nitric oxide (NO) concentration in the MCF-7 cells.     

Zirkonium-katalysierte Oxidation von primären aromatischen Aminen zu Nitroverbindungen mit tert-Butylhydroperoxid

Zirconium-catalysed Oxidation of Primary Aromatic Amines to Nitro Compounds Using tert-Butylhydroperoxide A broad range of primary aromatic amines ( 1a–x ) with electron donating and accepting substituents are oxidized in good to excellent yields to the nitro compounds 3a–x using tert-butylhydroperoxide as the oxidant and Zr(OtBu)₄ as the catalyst. The corresponding nitroso compounds 2m, 2n, 2s and 2u can be isolated in the conversion of electron-rich anilines 1m, 1n, 1s and 1u . The aminopyridines 5a–d are also converted to the corresponding nitropyridines 6a–d , but in lower yields (41–47%).