Mild and practical method for the alpha-arylation of nitriles with heteroaryl halides

[reaction: see text] A mild and transition-metal-free method for the alpha-arylation of aliphatic nitriles with activated heteroaryl halides was developed using NaHMDS or KHMDS as base at ambient temperature. The key to the success of this method is generation of the nitrile anion in the presence of the heteroaryl halide. The method is applicable to both primary and secondary carbonitriles and a wide range of heteroaryl halides. Selective monoarylation was observed with primary carbonitriles. The operational simplicity and the mild reaction conditions add to the value of this method as a practical alternative to the preparation of alpha-heteroaryl carbonitriles.     

Iminophosphines: synthesis, formation of 2,3-dihydro-1H-benzo[1,3]azaphosphol-3-ium salts and N-(pyridin-2-yl)-2-diphenylphosphinoylaniline, coordination chemistry and applications in platinum group catalyzed Suzuki coupling reactions and hydrosilylations

The aprotic and protic bi- and multidentate iminophosphines 2-Ph₂PC₆H₄N=CR¹R² (R¹=H, R²=Ph=2a; R¹=Me R²=Ph=2b; R¹=H, R²=2-thienyl=2c; R¹=H, R²=C₆H₄-2-PPh₂=2d; R¹=H, R²=C₆H₄-2-OH=2e, R¹=H, R²=C₆H₄-2-OH-3-Bu^t=2f; R¹=H, R²=CH₂C(O)Me=2g) have been prepared by the acid catalyzed condensation of 2-(diphenylphosphino)aniline with the corresponding aldehyde–ketone. Iminophosphine 2d can be reduced with sodium cyanoborohydride to give the corresponding amino-diphosphine 2-Ph₂PC₆H₄N(H)CH₂C₆H₄-2-PPh₂ (2h). In the presence of a stoichiometric quantity of acid, 2-(diphenylphosphino)aniline reacts in an unexpected manner with benzaldehyde, salicylaldehyde, or acetophenone to give the corresponding 2,3-dihydro-1H-benzo[1,3]azaphosphol-3-ium salts and with pyridine-2-carboxaldehyde to give N-(pyridin-2-ylmethyl)-2-diphenylphosphinoylaniline, the latter of which has been characterized by single-crystal X-ray crystallography, as its palladium dichloride derivative. The attempted condensation of 2-(diphenylphosphino)aniline with pyridine-2-carboxaldehyde to give the corresponding pyridine-functionalized iminophosphine resulted in an unusual transformation involving the diastereoselective addition of two equivalents of aldehyde to give 1,2-dipyridin-2-yl-2-(o-diphenylphosphinoyl)phenylamino-ethanol, which has been characterized by a single-crystal X-ray structure determination. The bidentate iminophosphine 2-Ph₂PC₆H₄N=C(H)Ph reacts with [(cycloocta-1,5-diene)PdClX] X=Cl, Me) to give [Pd{2-Ph₂PC₆H₄N=C(H)Ph}ClX] and the imino-diphosphine 2-Ph₂PC₆H₄N=C(H)C₆H₄-PPh₂ reacts with [(cycloocta-1,5-diene)PdClMe] to give [Pd{2-Ph₂PC₆H₄N=C(H)C₆H₄---PPh₂}ClMe] and each has been characterized by single-crystal X-ray crystallography. The monobasic iminophosphine 2-Ph₂PC₆H₄N=C(Me)CH₂C(O)Me reacts with [Ni(PPh₃)₂Cl₂] in the presence of NaH to give the phosphino–ketoiminate complex [Ni{2-Ph₂PC₆H₄N=C(Me)CHC(O)Me}Cl], which has been structurally characterized. Mixtures of iminophosphines 2a–h and a palladium source catalyze the Suzuki cross coupling of 4-bromoacetophenone with phenyl boronic acid. The efficiency of these catalysts show a marked dependence on the palladium source, catalysts formed from [Pd₂(OAc)₆] giving consistently higher conversions than those formed from [Pd₂(dba)₃] and [PdCl₂(MeCN)₂]. Catalysts formed from neutral bi- and terdentate iminophosphines 2a–d gave significantly higher conversions than those formed from their monobasic counterparts 2e–f. Notably, under our conditions the conversions obtained with 2a–c compare favorably with those of the standards; catalysts formed from tris(2-tolyl)phosphine and tris(2,4-di-tert-butylphenyl)phosphite and a source of palladium. In addition, mixtures of [Ir(COD)Cl]₂ and 2a–h are active for the hydrosilylation of acetophenone; in this case catalysts formed from monobasic iminophosphines 2e–f giving the highest conversions.     

Polymerization of diacetylenes by hydrogen bond templated adlayer formation

Adlayers were formed on self-assembled monolayers (SAMs) formed by alkanethiols on gold. Base SAMs exposing amide functional groups at the SAM surface were formed with 12-mercaptododecanamide. Adlayers of diacetylene-containing monomers were then formed via amide hydrogen bonding in decalin and decalin/toluene mixtures. Grazing angle FTIR, contact angle measurements, and ellipsometry suggest that these adlayer films exhibit ordering and packing similar to that of SAMs on gold. Resonance Raman spectroscopy showed that these diacetylene adlayers could be readily polymerized by exposure to UV light.     

Solvent-induced supramolecular isomerism in [Pt(S=C(NH2)2)4]2+ croconate salts

The role of solvent (and other species) in the formation of networks from tetrakis(thiourea)platinum(II) cations and croconate anions is examined, with crystallisations from DMSO giving rise to a structure containing solvent filled channels.     

Chiral conflict. The effect of temperature on the helical sense of a polymer controlled by the competition between structurally different enantiomers: from dilute solution to the lyotropic liquid crystal state

Helical polymers appended with paired structurally different enantiomers, which have opposing helical sense preferences, yield a new kind of relationship between optical activity and temperature, and also reveal unusual details of the nature of chiral interactions. Consistent with a statistical physical theory developed for these experiments, the proportion of the competing chiral groups, determined by synthesis, fixes the compensation temperature at which the helical senses are equally populated. The lyotropic liquid crystal state formed by these polymers yields therefore a nematic state at any chosen temperature over a very wide range, with a cholesteric state arising with tightening pitch as temperature deviates from this point. Far from the nematic temperature, the pitch reaches the nanometer scale and therefore the reflection of visible light. Before crossing zero at the nematic temperature, the optical activity becomes so large that it may be observed with the unaided eye through crossed polarizers.     

Engineering cytochrome P-450s

Cytochrome P-450 isozymes represent a critical component of nature’s spectrum of detoxification catalysts that could be exploited for bioremediation. The ethanol-inducible human cytochrome P-450 2E1 serves as a model eukaryotic P-450 that complements the bacterial P-450 cam in dehalogenation and detoxification of environmental pollutants. We explored the construction of novel chimeric P-450s using cytochrome P-450 camC and 2E1 genes. For construction of chimera 1 (478 amino acids, 55.14 kDa), 145 amino acids from the N-terminus of P-450 2E1 protein (493 amino acids, 56.84 kDa) were replaced with 130 amino acids from the N-terminus of P-450 camC protein (415 amino acids, 46.66 kDa). In chimera 2 (525 amino acids, 60.24 kDa) the strategy involves replacement of 28 amino acids in the C-terminus of chimera 1 with 75 amino acids from the C-terminus of P-450 camC gene. Homology models of both the chimeric proteins were developed using SWISS-MODEL based on the known crystal structure of cytochrome P-450 camC, BM-3, 1DT6A, and 2C17A. The models indicated that the proposed heme-binding site was intact, which is inevitable for catalytic activity of cytochrome P-450s. The expression of chimera 1 and 2 genes in Escherichia coli DH5α was evident from light-pink cell pellets, protein band in sodium dodecyl sulfate polyacrylamide gel electrophoresis, and diagnostic carbon monoxide-difference spectra. Our studies show that strategies can be developed to exploit the natural diversity of the P-450 superfamily to generate chimeric biocatalysts that would provide new templates amenable to directed evolution.     

Electrochemical doping of chirality-resolved carbon nanotubes

Raman spectra of electrochemically charged single-wall carbon nanotubes (HiPco) were studied by five different laser photon energies between 1.56 and 1.92 eV. The bands of radial breathing modes (RBM) were assigned to defined chiralities by using the experimental Kataura plot. The particular (n,m) tubes exhibit different sensitivity to electrochemical doping, monitored as the attenuation of the RBM intensities. Tubes which are in good resonance with the exciting laser exhibit strong doping-induced drop of the RBM intensity. On the other hand, tubes whose optical transition energy is larger than the energy of an exciting photon show only small changes of their RBM intensities upon doping. This rule presents a tool for analysis of mixtures of single-walled carbon tubes of unknown chiralities. It also asks for a re-interpretation of some earlier results which were reported on the diameter-selectivity of doping. The radial breathing mode in strongly n- or p-doped nanotubes exhibited a blue-shift. A suggested interpretation follows from the charging-induced structural changes of SWCNTs bundles, which also includes a partial de-bundling of tube ropes.     

Isolation and structure of [HC[CH(SiMe(3))(SnMe(3))](2)](+): a remarkably stable sec-alkyl cation

The reaction of the tin-substituted propene Me3Sn(R)CHCH=CHR (R = SiMe3) with MCl4 in dichloromethane in the presence of Me3SnCl gives the first examples of isolable sec-alkyl carbocation salts, [HC{CH(R)SnMe3}2]+M2Cl9- (M = Zr, Hf). The compounds are thermally stable and, unlike previously isolated trialkyl carbocations, do not require superacidic media or weakly coordinating anions for stability. The crystal structure and DFT calculations suggest polarization of the Sn substituents and hyperconjugation as the reason for the unexpected stability. The stabilizing effect of tin is significantly stronger than that of Si. The carbocations are effective initiators for the polymerization of isobutene, isoprene, and alpha-methylstyrene.     

The transfer between instruments of a reflectance near-infrared assay for paracetamol in intact tablets

This study compares several correction methods to facilitate the transfer of a validated near-infrared (NIR) assay for paracetamol in intact tablets between two reflectance NIR instruments of the same type. Transfer was defined as the ability to accurately predict the true assay value of a sample measured on a NIR system using an assay developed on a different system, and was assessed using a comprehensive set of statistical tests. Direct electronic transfer of the calibration models, representing the NIR assay, was not possible as a result of a definite residual spectrum between instruments. The use of a correction method based on the standardisation of the material used to record the reference spectrum also proved ineffective. Two methods investigated did succeed, the first employed a response surface calculated between the reflectance values of a set of six certified photometric standards measured on both instruments, with all full range partial least square (PLS) regression models subsequently transferred. The next was correction of the spectra from the second instrument utilising the residual spectrum between the mean sample of the validation set measured on both instruments. Through this approach all PLS regression models and also a single multiple linear regression (MLR) model were transferred. As an outcome of this study guidelines are suggested for the transfer of NIR assays along with the criteria deemed necessary to conclusively prove transfer and justify any correction method utilised. The significant criteria were determined to be the paired t-test with both the UV reference assay data and the original NIR assay data, and comparison of the coefficient of multiple determinations.     

A biological process for the reclamation of flue gas desulfurization gypsum using mixed sulfate-reducing bacteria with inexpensive carbon sources

A combined chemical and biological process for the recycling of flue gas desulfurization (FGD) gypsum into calcium carbonate and elemental sulfur is demonstrated. In this process, a mixed culture of sulfate-reducing bacteria (SRB) utilizes inexpensive carbon sources, such as sewage digest or synthesis gas, to reduce FGD gypsum to hydrogen sulfide. The sulfide is then oxidized to elemental sulfur via reaction with ferric sulfate, and accumulating calcium ions are precipitated as calcium carbonate using carbon dioxide. Employing anaerobically digested municipal sewage sludge (AD-MSS) medium as a carbon source, SRBs in serum bottles demonstrated an FGD gypsum reduction rate of 8 mg/L/h (10⁹ cells)^-1. A chemostat with continuous addition of both AD-MSS media and gypsum exhibited sulfate reduction rates as high as 1.3 kg FGD gypsum/m³d. The increased biocatalyst density afforded by cell immobilization in a columnar reactor allowed a productivity of 152 mg SO₄ ^-2/Lh or 6.6 kg FGD gypsum/m³d. Both reactors demonstrated 100% conversion of sulfate, with 75–100% recovery of elemental sulfur and chemical oxygen demand utilization as high as 70%. Calcium carbonate was recovered from the reactor effluent on precipitation using carbon dioxide. It was demonstrated that SRBs may also use synthesis gas (CO, H₂, and CO₂ in the reduction of gypsum, further decreasing process costs. The formation of two marketable products—elemental sulfur and calcium carbonate—from FGD gypsum sludge, combined with the use of a low-cost carbon source and further improvements in reactor design, promises to offer an attractive alternative to the landfilling of FGD gypsum.