Metallation reactions. Part 35: A change of the regiochemistry in the metallation of (alkylthio)arenes

The metallation reaction of bromo(alkylthio)benzenes is described. The results show the complementarity of these reactions with the metal-hydrogen exchange reaction. In fact, monometallation of bromo(methylthio)benzenes afforded products substituted in para or meta or ortho to the thioethereal function while bimetallation led to αS,para, αS,meta and αS,ortho disubstituted products. Analogously, the monometallation of 4-bromo-(isopropylthio)benzene afforded para-monosubstituted and ortho,para-disubstituted products.     

A novel method for the synthesis of 2,2-diaryl-1,1-difluoroethenes

β,β-Difluoro-α-phenylvinylstannane 3 was prepared in 60% yield from the reaction of β,β-difluoro-α-phenylvinylsulfone 2 with tributyltin hydride in refluxing benzene for 5 h. The cross-coupling reaction of 3 with aryl iodides bearing substituents such as proton, fluoro, chloro, bromo, methoxy, methyl, trifluoromethyl, and nitro on ortho, meta, para positions of the benzene ring in the presence of 10 mol % Pd(PPh₃)₄/10 mol % CuI afforded the corresponding 2,2-diaryl-1,1-difluoroethenes 4 in 22-82% yields.     

Metabromation du dimethyl-2,6 phenol et de son ether methylique en milieu superacide

In SbF₅-HF, reaction of bromine with 2,6-dimethylphenol gives the meta bromo compound 1b which is further halogenated to 3,4-dibromo-2,6-dimethylphenol 1c. In the same conditions ether 2a yields successively 2b and 2d. Meta bromination of compounds 1a,2a,2b implies electrophilic attack on the O-protonated substrate, whereas reaction of the neutral phenol 1b leads to the p-bromoderivative 1c. All products are obtained in excellent yields (> 85%).     

Pulsed fourier transform NMR of substituted aryltrimethyltin derivatives : II. (119Sn-13C) coupling constants and 13C chemical shifts of meta- and para-derivatives

Carbon-13 NMR data are reported for thirteen para- and meta-substituted phenyltrimethyltin compounds, RC₆H₄Sn(CH₃)₃, where R = para-N(CH₃)₂, para-OCH₃, para-OC₂H₅, para-CH₃, meta-CH₃, -H, para-F, meta-OCH₃, para-Cl, para-Br, meta-F, meta-Cl and para-Sn(CH₃)₃. In the para-derivatives, correlation coefficients with Hammet σ-constants of greater than ca. 0.9 are obtained with the tin-carbon couplings to methyl, C₁ and C₄ carbons, and with the carbon-13 chemical shifts δ(C(1)). In the meta-derivatives, the couplings |J(Sn-CH₃)|:, |:J(Sn-C(1))|:, |:J(Sn-C(3))|: and |:J(Sn-C(6))|:, and the shifts δ(C(1)) and δ(C(5)) correlate well with Hammett σ. In the para-derivatives, sensitivity to change in substituent falls off C(4) > C(3, 5) > C(1) > C(2, 6) > CH₃ as registered by the δ(C), while in the meta-derivatives δ(C) changes decrease C(3) > C(2), C(4) > C(1) > C(5), C(6) > CH₃. The magnitudes of the tin coupling constants decrease C(1) > CH₃ > C(3, 5) > C(2, 6) > C(4) in the para-derivatives, while in the meta-series the order is C(1) > CH₃ > C(3), C(5) > C(2) > C(6) > C(4). The two sets of one-bond |:J(Sn-CH₃)|: and |:J(Sn-C(1)|: values correspond closely to the 0.25/0.33 ratio of coefficients in the LCAO approach, and are interpreted in terms of s-electron redistributions at the tin atom with change in substituent.     

Design,Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors

Twelve pyridazinones (T1–T12) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. T6 was found to be the most potent MAO-B inhibitor with an IC₅₀ value of 0.013 µM, followed by T3 (IC₅₀ = 0.039 µM). Inhibitory potency for MAO-B was more enhanced by meta bromo substitution (T6) than by para bromo substitution (T7). For para substitution, inhibitory potencies for MAO-B were as follows: -Cl (T3) > -N(CH₃)₂ (T12) > -OCH₃ (T9) > Br (T7) > F (T5) > -CH₃ (T11) > -H (T1). T6 and T3 efficiently inhibited MAO-A with IC₅₀ values of 1.57 and 4.19 µM and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). T3 and T6 were found to be reversible and competitive inhibitors of MAO-B with K_i values of 0.014 and 0.0071, respectively. Moreover, T6 was less toxic to healthy fibroblast cells (L929) than T3. Molecular docking simulations with MAO binding sites returned higher docking scores for T6 and T3 with MAO-B than with MAO-A. These results suggest that T3 and T6 are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer’s disease.     

Formation of meta-arylsulfanyl- and meta-(alkylsulfanyl)phenols from cyclohexane-1,3-diones

Reaction of cyclohexane-1,3-diones with TsCl/Et₃N and treatment of the resulting 3-(tosyloxy)cyclohex-2-en-1-ones with aryl- or alkyl thiols and K₂CO₃ in MeCN gives 3-(arylsulfanyl)cyclohex-2-en-1-ones or 3-(alkylsulfanyl)cyclohex-2-en-1-ones, respectively. These compounds are easily brominated at C-2 by using NBS in MeCN; exposure to DBU in MeCN at room temperature then causes aromatization to afford meta-arylsulfanyl- and meta-(alkylsulfanyl)phenols.     

Synthesis of halogen-substituted borolanes and 2,3-dihydro-1H-boroles by reactions of aluminacarbocycles with boron trichloride and boron tribromide

A selective procedure has been developed for the synthesis of 1-chloro(bromo)-substituted borolanes and 2,3-dihydro-1H-boroles by reaction of aluminacarbocycles with boron trihalides BX₃ (X = Cl, Br). 3-Substituted 1-chloro(bromo)borolanes and 2,3-dihydro-1H-boroles have been isolated as individual substances, and their structure has been determined.     

Ionic liquid immobilization on carbon nanofibers and zeolites: Catalyst design for the liquid-phase toluene chlorination

The environmental-friendly chlorination reaction of toluene by trichloroisocyanuric acid (TCCA, C₃N₃O₃Cl₃) was investigated applying immobilized ionic liquids (ILs) on different supports. Ionic liquids were grafted either on carbon nanofibers (CNF) or encapsulated in zeolites. Their influence on the chlorination activity as well as on the selectivity in different chlorinated products was studied. An unusually high selectivity toward meta-chlorotoluene was achieved, up to 36%. Hence, the selectivity could be tuned to produce either expected ortho-/para-chlorotoluene or meta-chlorotoluene with a proper support choice.     

A new strategy for synthesis of polymeric supports with triazene linkers

A new strategy based on the use of diethylamine triazenes for stabilization and generation of polymer supported diazonium ions was described. New economical syntheses of four new polymeric supports with 3- and 6-carbon atom spacers and triazene linkers derived from meta- and para-aminophenol were described and compared to the traditional methods. The possible application of the polymer bound triazene masked diazonium salts as supports for immobilization of secondary amines (nortropine and 4-piperidinole and their esterification and oxidation), and as amine scavengers was shown. The new supports with meta-C₃-T2 and para-C₃-T2 linkers showed higher loadings and typically gave products with good yields and purities.     

Pulsed fourier transform NMR of substituted aryltrimethyltin derivatives : III. Proton data at 100 MHz and the derived Hammett σ-constant of the trimethyltin group

Proton NMR data at 100 MHz are reported for thirteen para- and meta-substituted phenyltrimethyltin compounds, XC₆H₄Sn(CH₃)₃, where X = para-N(CH₃)₂, para-OCH₃, para-OC₂H₅, para-CH₃, meta-CH₃, -H, para-F, meta-OCH₃, para-Cl, para-Br, meta-F, meta-Cl and para-Sn(CH₃)₃. Correlation coefficients with Hammett σ-constants of greater than 0.95 are obtained with the methyltin proton chemical shifts and coupling constants to carbon [¹J(¹³C¹H)] and tin [²J(SnC¹H)]. Solvent effects and other extraneous factors invalidate comparisons of ? values in terms of the relative attenuation of the transmission of substituent effects through homologous carbon, silicon, germanium and tin systems, but coupling constant data reflect a diminution of ca. one tenthfold per bond in the order ?[C(1)Sn] > ? [SnC] > ? [CH]. Satisfactory correlations (r > 0.95) are obtained in this series of closely-related compounds among the conventionally recorded two-bond, ²J(SnC¹H) and the constituent, one-bond ¹J (Sn¹³C) and J(¹³C¹H) coupling constants, but the correlation coefficient for the comparison between the two one-bond couplings, ¹J(Sn¹³C) and ¹J(¹³C¹H) is lower (r = 0.872). Changes in the couplings at the methyltin carbon bond tin-119 atoms are interpreted in terms of isovalent hybridization; a model based upon effective nuclear charges is tested with respect to both NMR coupling constants and ¹¹⁹Sn Mössbauer Isomer shifts at tin and is invalidated. Proton and carbon-13 NMR, chemical shift and coupling constant data are used to derive a Hammett σ-constant for the para-trimethyltin group of ?0.14, and the significance of this value is discussed.     

Spectrophotometric and conductometric study of copper(II) bromide-N,N-dimethylformamide solutions

Visible absorption spectra and the molar-conductance curve for CuBr₂ in N,N-dimethylformamide (DMF) as well as the spectra for the Cu(ClO₄)₂-Et₄NBr-DMF and CuBr₂-DMF-chlorobenzene systems have been studied. The results indicate the formation of the CuBr₃(DMF)⁻ complex being the predominating bromo complex of copper(II) in the most concentrated solutions of CuBr₂ in DMF. The stability constants of the individual bromo complexes of copper(II) have been determined: log β₁ = 3.35, logβ₂ = 5.4, and logβ₃ = 8.8.     

The reaction of H2PtCl6 with aromatic compounds in CF3COOH/H2O affording theanionic σ-aryl complexes of platinum(IV) : III. The sysnthesis of platinum (IV) complexes of benzenes containing electron-withdrawing substituents

The reaction of H₂PtCl₆ with nitrobenzene, o-nitrotoluene, benzoic acid, acetophenone and diphenyl in a CF₃COOH/H₂O mixture affords the anionic σ-aryl complexes of Pt^IV. In the case of monosubstituted benzenes, mixtures of meta- and para-platinated isomers were prepared. o-Nitrotoluene also gave rise to two isomers. Electron-witdrawing substituents decrease the rate of introducing the platinum moiety into benzene ring.     

Haloaza‐closo‐dodecaboranes

The bromo‐ and iodoaza‐closo‐dodecaboranes HNB₁₁H₁₀Hal (Hal = Br, I), MeNB₁₁H₉Br₂, and MeNB₁₁H₈Br₃ are formed from [NB₁₁H₁₁]^– and MeNB₁₁H₁₁, respectively, by electrophilic halogenation with elementary halogen in the presence of acidic catalysts. Hydrogen in para‐ or in para‐ and meta‐position with respect to the cluster‐N atom is substituted by halogen. With iodine chloride as halogenation agent, all the 11 boron bound H atoms of MeNB₁₁H₁₁ are substituted to give HNB₁₁Cl₅I₆ with iodine in the para‐ and meta‐ and chlorine in the ortho‐positions, presumably via electrophilic (I) and nucleophilic substitution (Cl). The products are characterized by their NMR spectra, the product HNB₁₁Cl₅I₆ also by crystal structure analysis.     

Structure of 1,4,10,19,25,41-C70(CF3)6, isomer with unique arrangement of addends

A novel isomer of C₇₀(CF₃)₆ has been isolated by HPLC from a mixture prepared by trifluoromethylation of C₇₀ with CF₃COOAg. The X-ray structure revealed an unprecedented arrangement of CF₃ groups forming a p³mp ribbon. This result provides additional evidence of the preferable formation of trifluoromethylated fullerene molecules comprising a single continuous ribbon of edge-sharing para- and meta-C₆(CF₃)₂ hexagons.     

Retrieval and analysis of transition states in electrophilic substitution reactions of the carborane(12) series

The transition states of the reaction of electrophilic substitution in a series of ortho-, meta-, and para-carboranes were found by calculations in the B3PW91/6-31G(d,p) and B3LYP/6-31G(d,p) approximations. The key role of catalyst was demonstrated in the reactions of halogenation and alkylation. The reaction selectivity of electrophilic alkylation by CH₃Br in the presence of AlCl₃ should be lower than that of the chlorination reaction.     

Selective catalytic carbanionic ethylation of methylphenols: influence of catalyst and substitution pattern

Addition of ethylene to the carbanions formed by the metallation of the lithium salts of di- and trimethylphenols by the strongly basic system, n-BuLi-LiK(OCH₂CH₂NMe₂)₂ provides a useful synthetic route to a range of alkylphenols. The ease of alkylation of the methyl groups decreases in the order ortho>meta>para while the inclusion of Mg(OCH₂CH₂OEt)₂ in the catalyst restricts alkylation to the methyl groups ortho to the hydroxy group. Dialkylation occurs only at the ortho-methyl groups and only if the adjacent meta-position is unsubstituted. The potential of these products for the synthesis of sterically hindered ligands is outlined.     

Chloride anion-induced dimer capsule based on a polyfluorinated macrocycle meta-WreathArene

[1_n]metacyclophanes are a class of important building blocks for supramolecular assembly of artificial capsules. Herein we present the preparation and properties of a novel polyfluorinated macrocycle meta-WreathArene, a C₂-symmetrical [1₄]metacyclophane. Adopting a cone conformation in acetone solution, the macrocycle can form dimer capsules through hydrogen bonds induced by chloride anions. Each dimer capsule consists of two meta-WreathArene and two chloride anions, and has been unambiguously characterized both in solution and in solid state.     

Synthesis and properties of novel aromatic poly(ester-imide)s bearing 1,5-bis(benzoyloxy)naphthalene units

Two series of new aromatic poly(ester-imide)s were prepared from 1,5-bis(4-aminobenzoyloxy)naphthalene (p-1) and 1,5-bis(3-aminobenzoyloxy)naphthalene (m-1), respectively, with six commercially available aromatic tetracarboxylic dianhydrides via a conventional two-stage synthesis that included ring-opening polyaddition to give poly(amic acid)s followed by chemical imidization to polyimides. The intermediate poly(amic acid)s obtained in the first stage had inherent viscosities of 0.41-0.84 and 0.66-1.37 dl/g, respectively. All the para-series and most of the meta-series poly(ester-imide)s were semicrystalline and showed less solubility. Two of the meta-series poly(ester-imide)s derived from less rigid dianhydrides were amorphous and readily soluble in polar aprotic solvents, and they could be solution-cast into transparent and tough films with good mechanical properties. The meta-series polymers derived from rigid dianhydrides were generally semicrystalline and showed less solubility. Except for one example, the meta-series poly(ester-imide)s displayed discernible T_gs in the range 239-273 °C by DSC. All of these two series poly(ester-imide)s did not show significant decomposition below 450 °C in nitrogen or in air.     

Stereoselective synthesis of key (η6-arene)Cr(CO)3 complexes to acorenone and acorenone B

Direct diastereoselective chromium complexation of meta-methoxy benzylalcohol derivatives was achieved by the introduction of Me₃,Si group, and the benzylic acetoxyl groups of the complexes were substituted with stereochemical retention to lead the key complexes to acorenone and acorenone B.     

Anion binding by meta ureido-substituted thiacalix[4]arenes

The regioselective nitration of 25,26,27,28-tetrapropoxythiacalix[4]arene (1,3-alternate) led to the formation of mono- and dinitro derivatives bearing NO₂ groups in the meta positions at the same side of the molecule. Their reduction and subsequent condensation with arylisocyanates gave the new types of anion receptors with a so far unknown meta-substitution pattern. In a highly HB-competitive solvent like DMSO, the novel ligands showed good complexation abilities. Moreover, as can be documented by higher complexation constants, achiral receptors 9a, 9b are better preorganized for anion binding than corresponding stereoisomers 10a, 10b. Our results indicate that anion receptors based on meta-substituted thiacalixarenes possess complexation abilities fully comparable with common para-substituted analogues.