(Z)‐7‐Chloro‐3‐[(3‐chloro­phenyl)­methyl­idene]‐4‐p‐tosyl‐3,4‐di­hydro‐2H‐1,4‐benzoxazine

In the title compound, C₂₂H₁₇Cl₂NO₃S, the mol­ecule is a substituted 3,4‐di­hydro‐2H‐1,4‐benzoxazine compound which has three phenyl rings which are essentially planar. The 3,4‐di­hydro‐2H‐oxazine part of the mol­ecule is fused to the benzo ring and has a half‐boat conformation; the dihedral angle between the planar part of the oxazine ring and the benzo ring is 10.2 (2)°. The (3‐chloro­phenyl)­methyl­idene substituent has a Z configuration in relation to the ring N atom of the oxazine moiety. Interestingly, the p‐toluenesulfonyl (p‐tosyl) substituent on the ring N atom protrudes away from the 3‐­chloro­phenyl substituent thus avoiding any steric interaction.     

Radical‐initiated polymerization of β‐methyl‐α‐methylene‐γ‐butyrolactone

β‐Methyl‐α‐methylene‐γ‐butyrolactone (MMBL) was synthesized and then was polymerized in an N,N‐dimethylformamide (DMF) solution with 2,2‐azobisisobutyronitrile (AIBN) initiation. The homopolymer of MMBL was soluble in DMF and acetonitrile. MMBL was homopolymerized without competing depolymerization from 50 to 70 °C. The rate of polymerization (R_p) for MMBL followed the kinetic expression R_p = [AIBN]^0.54[MMBL]^1.04. The overall activation energy was calculated to be 86.9 kJ/mol, k_p/k_t^1/2 was equal to 0.050 (where k_p is the rate constant for propagation and k_t is the rate constant for termination), and the rate of initiation was 2.17 × 10^?8 mol L^?1 s^?1. The free energy of activation, the activation enthalpy, and the activation entropy were 106.0, 84.1, and 0.0658 kJ mol^?1, respectively, for homopolymerization. The initiation efficiency was approximately 1. Styrene and MMBL were copolymerized in DMF solutions at 60 °C with AIBN as the initiator. The reactivity ratios (r₁ = 0.22 and r₂ = 0.73) for this copolymerization were calculated with the Kelen–Tudos method. The general reactivity parameter Q and the polarity parameter e for MMBL were calculated to be 1.54 and 0.55, respectively. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1759–1777, 2003     

Linear Free‐Energy Relationships Applied to the 13C NMR Chemical Shifts in 4‐Substituted N‐[1‐(Pyridine‐3‐ and ‐4‐yl)ethylidene]anilines

Two series of 4‐substituted N‐[1‐(pyridine‐3‐ and ‐4‐yl)ethylidene]anilines have been synthesized using different methods of conventional and microwave‐assisted synthesis, and linear free‐energy relationships have been applied to the ¹³C NMR chemical shifts of the carbon atoms of interest. The substituent‐induced chemical shifts have been analyzed using single substituent parameter and dual substituent parameter methods. The presented correlations describe satisfactorily the field and resonance substituent effects having similar contributions for C1 and the azomethine carbon, with exception of the carbon atom in para position to the substituent X. In both series, negative ρ values have been found for C1′ atom (reverse substituent effect). Quantum chemical calculations of the optimized geometries at MP2/6‐31G++(d,p) level, together with ¹³C NMR chemical shifts, give a better insight into the influence of the molecular conformation on the transmission of electronic substituent effects. The comparison of correlation results for different series of imines with phenyl, 4‐nitrophenyl, 2‐pyridyl, 3‐pyridyl, 4‐pyridyl group attached at the azomethine carbon with the results for 4‐substituted N‐[1‐(pyridine‐3‐ and ‐4‐yl)ethylidene]anilines for the same substituent set (X) indicates that a combination of the influences of electronic effects of the substituent X and the π₁‐unit can be described as a sensitive balance of different resonance structures.     

Isocyanide‐Based Three‐Component Synthesis of Highly Substituted 1,6‐Dihydro‐6,6‐dimethylpyrazine‐2,3‐dicarbonitrile, 3,4‐Dihydrobenzo[g]quinoxalin‐2‐amine,and 3,4‐Dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine Derivatives

A novel and efficient isocyanide‐based multicomponent reaction between alkyl or aryl isocyanides 1 , 2,3‐diaminomaleonitrile ( 2 ), naphthalene‐2,3‐diamines ( 6 ) or benzene‐1,2‐diamine ( 9 ), and 3‐oxopentanedioic acid ( 3 ) or Meldrum's acid ( 4 ) or ketones 7 was developed for the ecologic synthesis, at room temperature under mild conditions, of 1,6‐dihydropyrazine‐2,3‐dicarbonitriles 5a – 5f in H₂O without using any catalyst, and of 3,4‐dihydrobenzo[g]quinoxalin‐2‐amine and 3,4‐dihydro‐3,3‐dimethyl‐quinoxalin‐2‐amine derivatives 8a – 8g and 10a – 10e , respectively, in the presence of a catalytic amount of p‐toluenesulfonic acid (TsOH) in EtOH, in good to excellent yields (Scheme 1).     

An Efficient Synthesis of Optically Active trans‐(3R,4R)‐3‐Acetoxy‐4‐aryl‐1‐(chrysen‐6‐yl)azetidin‐2‐ones Using (+)‐Car‐3‐ene as a Chiral Auxiliary

An efficient enantioselective synthesis of 3‐acetoxy trans‐β‐lactams 7a and 7b via [2+2] cycloaddition reactions of imines 4a and 4b , derived from a polycyclic aromatic amine and bicyclic chiral acid obtained from (+)‐car‐3‐ene, is described. The cycloaddition was found to be highly enantioselective, producing only trans‐(3R,4R)‐N‐azetidin‐2‐one in very good yields. This is the first report of the synthesis of enantiomerically pure trans‐β‐lactams 7a and 7b with a polycyclic aromatic substituent at N(1) of the azetidin ring.     

Multicomponent Transformation of Isoindoline‐1,3‐diimine (=1H‐Isoindole‐1,3(2H)‐diimine), Acetylenic Esters,and Triphenylphosphine to Novel Dihydropyrimido[2,1‐a]isoindole Derivatives

The three‐component reaction of the zwitterions generated from dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates and triphenylphosphine (Ph₃P) with isoindoline‐1,3‐diimine (=1H‐isoindole‐1,3(2H)‐diimine) is described (Scheme 1). This reaction affords the corresponding special type of substituted dihydropyrimido[2,1‐a]isoindole derivatives in good yields without using any catalyst and activation (Table).     

Palladium(II)‐catalyzed cyclization of W‐(2′,4′‐dienyl)‐2‐alkynamides to α‐alkylidene‐γ‐butyrolactams

In the presence of CuCl₂, N‐(2′, 4′‐dienyl)‐2‐alkynamides can be converted to α‐alkylidene‐σ‐butyrolactams under the catalysis of palladium(II). In this reaction, CuCl₂ is used to oxidize Pd(0) to regenerate Pd(II), or the carbon‐palladium bond is quenched by the oxidative cleavage reaction of CuCl₂.     

Cyclic (Amino)(aryl)carbenes (CAArCs) as Strong σ‐Donating and π‐Accepting Ligands for Transition Metals

Cyclic (amino)(aryl)carbenes (CAArCs) result from the replacement of the alkyl substituent of cyclic (alkyl)(amino) carbenes (CAACs) by an aryl group. This structural modification leads to enhanced electrophilicity of the carbene center with retention of the high nucleophilicity of CAACs, and therefore CAArCs feature a small singlet–triplet gap. The isoindolium precursors are readily prepared in good yields, and deprotonation at low temperature, in the presence of [RhCl(cod)]₂ and [(Me₂S)AuCl] lead to air‐stable rhodium and gold CAArC‐supported complexes, respectively. The rhodium complexes promote the [3+2] cycloaddition of diphenylcyclopropenone with ethyl phenylpropiolate, and induce the addition of 2‐vinylpyridine to alkenes by CH activation. The gold complexes allow for the catalytic three‐component preparation of 1,2‐dihydroquinolines from aniline and phenyl acetylene. These preliminary results illustrate the potential of CAArC ligands in transition‐metal catalysis.     

Calculated geometries of dications of bis odd‐membered π‐ring systems containing a NCN fragment and related π‐systems. An opposite out‐of‐plane rotation of the 4n π‐ring subsystems

Quantum chemical calculations have been carried out on dications of bis odd‐membered π‐ring systems containing a NCN fragment and related π‐systems. An opposite out‐of‐plane rotation of both subsystems was found if these systems contain 4n π‐electrons (antiaromatic). A planar situation was found for 4n+2 π‐electrons (aromatic). The geometric representations could be compared with X‐ray crystallographic three‐dimensional structures of related compounds. Calculations at different levels clearly show that separation of the σ‐ and π‐electron contribution is an effective way to elucidate the origin of the geometrical changes. We also give attention to some fundamental aspects of the subsystems related to the 1,3‐azolium cations because of their biochemical relevance such as fast C₂? H proton exchange. We postulate that at least two molecules of water are involved in this process. The significance of a trigonal pyramidal (TP) geometry has been emphasized. © 2001 Wiley Periodicals, Inc. Int J Quantum Chem, 2001     

Lewis Acid‐Mediated Addition of Amino Acid‐Substituted α‐Allylsilanes to Aromatic Acetals

Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid‐activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2‐(N‐PG‐amino)‐3‐(trimethylsilyl)pent‐4‐enoate and methyl (E)‐2‐(N‐PG‐amino)‐3‐(trimethylsilyl)hex‐4‐enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl₄ was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl₄ was required to achieve high yields, whereas 2 equiv. of BF₃?OEt₂ were required for comparable outcomes. Excellent selectivity (>99% syn/anti) and high yield (up to 89%) were obtained with halo‐substituted aromatic acetals, while more electron‐rich electrophiles led to both lower yields and diastereoselectivities.     

Functionalization of Quinazolin‐4‐ones Part 1: Synthesis of Novel 7‐Substituted‐2‐thioxo Quinazolin‐4‐ones from 4‐Substituted‐2‐Aminobenzoic Acids and PPh3(SCN)2

4‐(Nitro, amino, acetylamino)‐2‐aminobenzoic acid were allowed to react with PPh₃(SCN)₂ and gave the crossholding 7‐nitro, 7‐acetylamino‐ and 7‐amino‐2‐thioxo quinazolin‐4‐ones respectively. The nature of the substituent at position 4 of the 2‐aminobenzoic acids has significant influence on the outcome of the cyclisation reaction with PPh₃(SCN)₂. Similarly, the nature of the substituent at position 7 of the 2‐substituted quinazolin‐4‐ones significantly affected the ease with which alkylation reactions could be performed. The alkylation selectivity of the 7‐ substiuted‐2‐thioxo quinazolin‐4‐ones was found to depend on the nature of the alkyl halide and the nature of the substituent at position 2.     

The Development of a Stereoselective Method for the Synthesis of Tetrasubstituted Derivatives of α,β‐Unsaturated Carboxylic Acids

Alkenes possessing four different carbon‐linked substituents are the main structural motif of many biologically active compounds. The derivatives of (2E)‐3‐(3‐methoxyphenyl)‐2‐methylpent‐2‐enoic acid ((E)‐ 2c ) are suitable precursors for the synthesis of Tapentadol, a novel centrally acting analgesic. It was found that the Ni‐carbometallation reaction of disubstituted alkyne 8 with CO₂ and an Et₂Zn allows for efficient and practical preparation of (E)‐ 2c as a single (E)‐regioisomer in 89% of isolated yield. The influence of the size of the aliphatic substituent of alkyne and the steric hindrance of the organozinc reagent on stereochemical course of the carbometallation reaction was evaluated. Finally, air‐stable Ni(dme)Cl₂ was proposed as an alternative to widely used Ni(cod)₂ catalyst.     

Electrochemical Investigation of Na‐Salt of 2‐Methyl‐3‐(4‐nitrophenyl)acrylate on Glassy Carbon Electrode

The electrochemical behavior of Na‐salt of 2‐methyl‐3‐(4‐nitrophenyl)acrylate (NPA) and its reduction product was studied by cyclic (CV), differential pulse(DPV) and square wave voltammetry (SWV) using a glassy carbon electrode (GCE). The results revealed that NPA is irreversibly reduced leading to the formation of a reduction product (P_NPA). For pH<9.0 the peak potential was linearly dependent on pH. For pH>9.0 the peak potential was pH‐independent and the value of pK_b≈9.0 was determined. The adsorbed P_NPA exhibited reversible redox reaction. The reduction of P_NPA was pH dependent. To ensure that the electrochemical behavior of NPA is due to the reducible moiety, NO₂, closely related compounds to NPA were also studied, and a redox mechanism was proposed for NPA.     

Enantioselective Nucleophilic β‐Carbon‐Atom Amination of Enals: Carbene‐Catalyzed Formal [3+2] Reactions

An enantioselective β‐carbon amination for enals is disclosed. The nitrogen atom from a protected hydrazine with suitable electronic properties readily behaves as a nucleophile. Addition of the nitrogen nucleophile to a catalytically generated N‐heterocyclic‐carbene‐bound α,β‐unsaturated acyl azolium intermediate constructs a new carbon–nitrogen bond asymmetrically. The pyrazolidinone products from our catalytic reactions are common scaffolds in bioactive molecules, and can be easily transformed into useful compounds such as β³‐amino‐acid derivatives.     

Synthesis of α‐(Fluorophenyl)pyridine by Palladium‐Catalyzed Cross‐Coupling Reaction

A series of α‐(fluoro‐substituted phenyl)pyridines have been synthesized by means of a palladium‐catalyzed cross‐coupling reaction between fluoro‐substituted phenylboronic acid and 2‐bromopyridine or its derivatives. The reactivities of the phenylboronic acids containing di‐ and tri‐fluoro substituents with α‐pyridyl bromide were investigated in different catalyst systems. Unsuccessful results were observed in the Pd/C and PPh₃ catalyst system due to phenylboronic acid containing electron‐withdrawing F atom(s). For the catalyst system of Pd(OAc)₂/PPh₃, the reactions gave moderate yields of 55% –80%, meanwhile, affording 10% –20% of dimerisation (self‐coupling) by‐products, but trace products were obtained in coupling with 2,4‐difluorophenylboronic acids because of steric hinderance. Pd(PPh₃)₄ was more reactive for boronic acids with sterically hindering F atom(s), and the coupling reactions gave good yields of 90% and 91% without any self‐coupling by‐product.     

The First Metal‐Carbon Bond β‐Isomer Paddlewheel Pd24+ Compounds

The first metal‐carbon bond β‐form paddlewheel complexes containing a Pd₂⁴⁺ core, [Pd(η²‐dithio)]₂(μ‐dppa)( μ‐SCNMe₂) (dithio = S₂P(OEt)₂, 2 ; S₂COEt, 3 ; S₂CNC₄H₈, 4 ), were prepared by the reactions of the α‐form paddlewheel‐type Pd₂⁺⁴ dipalladium complex [Pd₂ (μ‐Hdppa)₂(μ‐SCNMe₂)₂][Cl]₂, 1 with various dithio‐ligands, [NH₄][S₂P(OEt)₂], [K][S₂COEt] and [NH₄][S₂CNC₄H₈], in methanol at ambient temperature (Hdppa = bis(diphenylphosphino)amine). Electronic spectra and two X‐ray structures of the Pd₂⁺⁴ species have been determined.     

2‐Ethylsulfanyl‐7‐(furan‐2‐yl)‐4‐(thiophen‐2‐yl)pyrazolo[1,5‐a][1,3,5]triazine: π‐stacked chains of hydrogen‐bonded R22(10) dimers

In the title compound, C₁₅H₁₂N₄OS₂, the bond distances in the fused heterocyclic system show evidence for aromatic‐type delocalization in the pyrazole ring with some bond fixation in the triazine ring. The thiophenyl substituent is slightly disordered over two sets of atomic sites having occupancies of 0.934 (4) and 0.066 (4). The non‐H atoms in the entire molecule are nearly coplanar, with the planes of the furanyl substituent and the major orientation of the thiophenyl substituent making dihedral angles of 5.72 (17) and 1.8 (3)°, respectively, with that of the fused ring system. Molecules are linked into centrosymmetric R₂²(10) dimers by C—H...O hydrogen bonds and these dimers are further linked into chains by a single π–π stacking interaction. Comparisons are made with some related 4,7‐diaryl‐2‐(ethylsulfanyl)pyrazolo[1,5‐a][1,3,5]triazines which contain variously substituted aryl groups in place of the furanyl and thiophenyl substituents in the title compound.     

Mechanistic Insights into an Unexpected Carbon Dioxide Insertion Reaction through the Crystal Structures of Carbamic Diphenylthiophosphinic Anhydride and l‐[(4‐Nitrophenyl)‐sulfonyl]‐trans‐2,5‐pyrrolidinedicarboxylic Acid Methyl Ester

The crystal structures of an unexpected carbon dioxide inserted carbamidiphenylthiophosphinic anhydride and l‐[(4‐nitrophenyl) sulfonyl]‐trans‐2, 5‐pyrrolidinedicarboxylic acid methyl ester were determined by X‐ray analysis. They crystallized in the space group P2₁(#4) with a =0.9550(2), b = 0.9401(4), c= 1.2880(2) nm, β= 107.74°, V= 1.1013 (5) nm³, D_caled= 1.349 g/cm³, Z = 2 and P2₁2₁2₁(# 19) with a = 1.4666(2), b = 0.7195(2), c = 1.6339(2) nm, V = 1.7240(7) nm³, D_caled = 1.434 g/cm³, Z = 4, respectively. Through the investigation of these two crystal structures, the mechanistic insights into this unexpected carbon dioxide insertion in the reaction of trans‐2,5‐disubstituted pyrrolidine with diphenylthiophosphoryl chloride in the presence of potassium carbonate were disclosed.     

Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β2‐Amino Acids

A convergent, organocatalytic asymmetric aminomethylation of α,β‐unsaturated aldehydes by N‐heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehyde‐derived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox‐neutral strategy is suitable for the scalable synthesis of enantiomerically enriched β²‐amino acids bearing various substituents.     

6‐[3‐Hydroxy‐17‐oxoestra‐1,3,5(10)‐trien‐7β‐yl]­hexane­nitrile

In the title compound, C₂₄H₃₁NO₂, ring B adopts a conformation between the boat and twisted‐boat forms. This conformation best accommodates adverse intramolecular H⋯H interactions between the H atoms of the 7β‐substituent and the two nearest ring H atoms. The tilt angle between rings A and D is 28.6 (1)°.