An improved preparation of 3,5-bis(trifluoromethyl)acetophenone and safety considerations in the preparation of 3,5-bis(trifluoromethyl)phenyl Grignard reagent

An improved and efficient bromination of 3,5-bis(trifluoromethyl)benzene was developed. A safe and reliable preparation of the potentially explosive 3,5-bis(trifluoromethyl)phenyl Grignard and 3-trifluoromethylphenyl Grignard reagents, from the precursor bromides, is described. Reaction System Screening Tool (RSST) and Differential Thermal Analysis (DTA) studies suggest these trifluoromethylphenyl Grignard reagents can detonate on loss of solvent contact or upon moderate heating. When prepared and handled according to the methods described herein, these Grignard reagents can be safely prepared and carried on to advanced intermediates.     

3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.     

Novel H2 activation by a tris[3,5-bis(trifluoromethyl)phenyl]borane frustrated Lewis pair

Tris[3,5-bis(trifluoromethyl)phenyl]borane (1, BArF(18)), has been synthesised on a practical scale for the first time. According to the Gutmann-Beckett method it is a more powerful Lewis acid than B(C(6)F(5))(3). It forms a 'frustrated Lewis pair' with 2,2,6,6-tetramethylpiperidine which cleaves H(2) to form a salt containing the novel anion [μ-H(BArF(18))(2)](-).     

Solvent-dependent resonance Raman spectra of high-valent oxomolybdenum(V) tris[3,5-bis(trifluoromethyl)phenyl]corrolate

UV-visible, infrared (IR), and resonance Raman (RR) spectra were measured and analyzed for a high-valent molybdenum(V)-oxo complex of 5,10,15-tris[3,5-bis(trifluoromethyl)phenyl]corrole (1) at room temperature. The strength of the metal-oxo bond in 1 was found to be strongly solvent-dependent. Solid-state IR and RR spectra of 1 exhibited the MoVO stretching vibration at nu(MoVO)=969 cm(-1). It shifted up by 6 cm(-1) to 975 cm(-1) in n-hexane and then gradually shifted to lower frequencies in more polar solvents, down to 960 cm(-1) in dimethyl sulfoxide. The results imply that stronger acceptor solvents weaken the MoVO bond. The 45-cm(-1) frequency downshifts displayed by 1 containing an 18O label in the molybdenum(V)-oxo unit confirmed the assignments for the observed IR and RR nu(MoVO) bands. The solvent-induced frequency shift for the nu(MoVO) RR band, measured in a series of 25 organic solvents ranging from n-hexane (AN=0.0) to N-methylformamide (AN=32.1), did not decrease in direct proportion to Gutmann's solvent acceptor numbers (ANs). However, a good linear correlation of the nu(MoVO) frequency was found against an empirical "solvent polarity" scale (A+B) of Swain et al. J. Am. Chem. Soc. 1983, 105, 502-513. A molecular association was observed between chloroform and oxomolybdenum(V) corrole 1 through MoO...H/CCl3 hydrogen-bonding interactions. This association manifested itself as a shift of the nu(MoVO) RR band of 1 in CDCl3 to a higher frequency compared to that in CHCl3.     

可逆性化学反应结合HPLC测定氨丙基硅胶表面上氨基的含量

采用苯甲醛与氨丙基硅胶表面上的氨基反应形成希夫碱,再将其水解为苯甲醛,通过HPLC测定水解后苯甲醛的量,可以间接测定硅胶表面上所链接的氨基量,从而建立了一种测定氨丙基硅胶表面上氨基含量的方法.希夫碱的生成与水解最佳条件分别为:40℃反应1 h;40℃,pH 6.0超声反应1 h;色谱条件:PHENOMENEX Luna C18(150 mm×4.6mm,5μm)色谱柱,流动相:V(乙腈):V(水)=50:50,柱温30℃,紫外检测波长246 nm,流速1.0 mL/min.苯甲醛的线性范围为1.0～50.0 mg/L(r=0.9999),平均回收率100.8%,RDS为1.6%.该方法对氨丙基硅胶没有破坏性,测定完后的硅胶可回收使用,适用于氨丙基硅胶表面上氨基的含量测定.     

Persistent phosphinyl radicals featuring a bulky amino substituent and the 2,6-bis(trifluoromethyl)phenyl group

Persistent phosphinyl radicals featuring the 2,6-bis(trifluoromethyl)phenyl group were prepared and characterized. Their electronic structure was theoretically investigated, and their low-temperature dimerization into the corresponding diphosphines was found to be strongly inhibited when the sterically very demanding (tert-butyl)(trimethylsilyl)amino substituent was used.     

Rhodium-tris(3,5-bis(trifluoromethyl)phenyl)phosphine catalyzed hydroformylation of dienes to dialdehydes in supercritical carbon dioxide with high activity

Rhodium-catalyzed hydroformylation of 1,5-hexadiene and 1,7-octadiene to corresponding dialdehydes was investigated in compressed CO₂ and in toluene using different fluorinated phosphine compounds as ligands. A rhodium complex using tris(3,5-bis(trifluoromethyl)phenyl)phosphine is highly effective in compressed CO₂ for double hydroformylation of 1,5-hexadiene, whose TOF value is much larger than those reported so far. It has been shown that this ligand is effective also for the hydroformylation of 1,7-octadiene and scCO₂ is a better solvent than a conventional organic solvent of toluene for the title reaction.     

Characterization of amino acids in silk sericin protein from Gonometa rufobrunnae by MEKC with phenyl isothiocyanate derivatization

An MEKC method was developed for the separation and characterization of phenyl-isothiocyanate (PITC)-labeled amino acids derived from Gonometa rufobrunnae silkworm after microdialysis sample cleanup. The influence of the buffer and SDS concentration on the resolution of the amino acids was investigated. A buffer system consisting of 25 mM phosphate, 10 mM borate buffer at pH 9.00, and 70 mM SDS showed the best results, with 13 PITC-amino acid derivatives being resolved out of 15 possible amino acids that were under study. Microdialysis sampling demonstrated its efficiency as a sample cleanup technique. Sericin protein from G. rufobrunnae was found to be characterized by at least 11 positively identified amino acids. These included His, Tyr, Ser, Ala, Phe, Lys, Gly, Arg, Cys, Glu, and Asp. Leu/Met and Val/Thr were coeluting pairs and hence could not be positively confirmed.     

Microbial and homogenous asymmetric catalysis in the reduction of 1-[3,5-bis(trifluoromethyl)phenyl]ethanone

Two complementary approaches for the enantioselective reduction of 1-[3,5-bis(trifluoromethyl)phenyl]ethanone 1 are described and compared: microbial versus asymmetric reduction of ketones through asymmetric hydrogen transfer. Among the various microorganisms screened, Lactobacillus kefir and Aspergillus niger reduced ketone 1 to the corresponding (R)-alcohol (R)-2. The (S)-alcohol (S)-2 was obtained by reduction of 1 using homogenous asymmetric catalysis. The configuration of the alcohol in both the biocatalysis and hydrogen transfer approaches was controlled by the choice of the enzyme and by the configuration of ligands, respectively. Both enantiomers were obtained in high yield and ee.     

Determination of beta-aspartylpeptidase activity in human faeces by high-performance liquid chromatography using pre-column derivatization with phenyl isothiocyanate

Bacterial enzymes are responsible for degradation of beta-aspartyl peptides in the intestinal tract. These peptides, especially the dipeptide beta-aspartylglycine, are useful as indicators of an impaired anaerobic intestinal microflora of antibiotic-treated patients. A method to separate the dipeptides beta-aspartylalanine, beta-aspartylglutamine, beta-aspartylglycine and beta-aspartylserine, using reversed-phase high-performance liquid chromatography and precolumn derivatization with phenyl isothiocyanate, was developed. This method was used to determine beta-aspartylpeptidase activity in faecal supernatants of healthy human volunteers and antibiotic-treated patients with beta-aspartylglycine as substrate. This activity was absent in the antibiotic-treated group, while in individuals with an intact intestinal flora it ranged from 16 to 100% degradation per 18 h. In addition, it was found that faecal enzyme preparations cleaved beta-aspartylglycine at a much lower rate than the other beta-aspartyl peptides.     

Application of amino acid analysis by high-performance liquid chromatography with phenyl isothiocyanate derivatization to the rapid determination of free amino acids in biological samples.

An amino acid analysis by reversed-phase high-performance liquid chromatography after precolumn derivatization with phenyl isothiocyanate was adapted to the determination of free amino acids in plasma or other biological fluids and in tissue homogenates. Preparation of samples included deproteinization by 3% sulphosalicylic acid, and careful removal under high vacuum of residual phenyl isothiocyanate after derivatization. A Waters Pico-Tag column (15 cm long) was used, immersed in a water-bath at 38 degrees C. In rat or human plasma, separation of 23 individual amino acids, plus the unresolved pair tryptophan and ornithine, was obtained within 13 min. Including the time for column washing and re-equilibration, samples could be chromatographed at 23-min intervals. Variability was tested for each amino acid by calculating the coefficients of variation of retention times (less than 1% in the average) and peak areas (less than 4% for both intra-day and inter-day determinations). The linearity for each standard amino acid was remarkable over the concentration range 3-50 nmol/ml. The mean recovery of amino acid standards added to plasma prior to derivatization was 97 +/- 0.8%, except for aspartate (82%) and glutamate (81%). This method is rapid (almost three samples per hour can be analysed, more than in any other reported technique), with satisfactory precision, sensitivity and reproducibility. Therefore, it is well suited for routine analysis of free amino acids in both clinical and research work.     

Complexation of trimeric copper(i) and silver(i) 3,5-bis(trifluoromethyl)pyrazolates with amine-borane

A complexation of trimeric copper(i) and silver(i) 3,5-bis(trifluoromethyl)pyrazolates ((ML)₃) with BH₃NEt₃ was studied by IR spectroscopy in hexane and dichloromethane solutions. In hexane, two complexes [(ML)₃][BH₃NEt₃]₂ (1) and [(ML)₃][BH₃NEt₃] (2) were formed depending on the ratio of reagents. In dichloromethane, only one complex [(ML)₃][BH₃NEt₃] (2) was found. The thermodynamic parameters (ΔH ^○, ΔS ^○) of complex 1 in hexane and complex 2 in dichloromethane were obtained. The complex [(AgL)₃][BH₃NEt₃] was isolated in the solid state, its structure was established by X-ray diffraction. The complex is formed due to two bridges B-H-Ag, one BH group is not involved in the complexation. In crystal, molecules 2 form supramolecular dimers due to the intermolecular interactions between metals of two macrocycles.     

Reaction of 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole with primary amines. Synthesis of 4-substituted-3,5-bis(trifluoromethyl)-4H-1,2,4-triazoles

Reaction of 3,5-bis(trifluoromethyl)-1,3,4-oxadiazole ( 1a ) with primary amines under a variety of conditions conveniently produced 4-substituted-3,5-bis(trifluoromethyl)-4H-1.2,4-triazoles 4a in 26-85% yield. Alkyl amines reacted with 1a in methanol at ?42° to provide hydrogen-bonded monoadduct-methanol complexes 5a , as determined by X-ray. The reaction of 1a with sterically hindered or strongly electron deficient anilines required high temperatures in the absence of solvent.     

Synthesis, structural characterization, and initial electroluminescent properties of bis-cycloiridiated complexes of 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine

A series of bis-cyclometalated Ir(III) complexes (8-10, 12, 15, 17, 19, 21, 23, 25, 28, 29 and 33) bearing two chromophoric N^∧C cyclometalated ligands derived from 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine (1) and a third nonchromophoric ligand has been synthesized. A palladium-catalyzed cross-coupling reaction between 2-chloro-4-methylpyridine (2) and 3,5-bis(trifluoromethyl)phenylboronic acid (3) was used to prepare 2-(3,5-bis(trifluoromethyl)phenyl)-4-methylpyridine (1). Cyclometalation of (1) by IrCl₃ was carried out in (MeO)₃PO, with the formation of chloro-bridged dimer [N^∧C]₂Ir(μ-Cl)₂Ir[C^∧N]₂ (8). Reaction of (8) with lithium 2,4-pentanedionate, lithium 2,2,6,6-tetramethyl-heptane-3,5-dionate (13), dipivaloyltrimethylsilylphosphine (14), 2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octadione (16), 1,1,1,3,3,3-hexafluoro-2-pyridin-2-yl-propan-2-ol (18), 1,1,1,3,3,3-hexafluoro-2-pyrazol-1-ylmethyl-propan-2-ol (20), 2-diphenylphosphanylethanol (22), and 1-diphenylphosphanylpropan-2-ol (24), afforded octahedral iridium complexes 9, 12, 15, 17, 19, 21, 23 and 25, respectively. Complex 10, which contains three different ligands (L₁ = N^∧C of 1; L₂ = N^∧C of 4,4′-dimethyl-[2,2′]bipyridinyl 4; L₃ = O^∧O of 2,4-pentanedione), and complex 11, which contains no cyclometalated ligands (L₁ = 4; L₂ = L₃ = Cl; L₄ = O^∧O of 2,4-pentanedione) were also isolated as minor products in a one-pot reaction between a 94:5 mixture of 1 and 4, IrCl₃ and lithium 2,4-pentanedionate. Reaction of 8 with diphenylphosphanylmethanol (27) in 1,2-dichloroethane unexpectedly led to complexes 28 and 29. The reactions of 8 with benzoylformic acid resulted in the formation of hydroxyl-bridged dimer [N^∧C]₂Ir(μ-OH)₂Ir[C^∧N]₂ (33). According to X-ray analyses, Ir-to-Ir distances in the crystal cell increase from 6.86 Å for 10 to 13.31 Å for 33. The angle theta, which represents the twisting of two cyclometalated C-Ir-N planes relative to each other, varies from 97.5° for 21 to 90.76 for complex 28. OLED devices were fabricated from several Ir complexes and preliminary results are discussed.     

Synthesis,structures and photophysical properties of phosphorus-containing silver 3,5-bis(trifluoromethyl)pyrazolates

Reaction of a trinuclear silver pyrazolate {[3,5-(CF₃)₂Pz]Ag}₃ complex with tricyclohexylphosphine at different reagent ratios leads to the formation of heteroleptic dinuclear or tetranuclear complexes. According to the single crystal X-ray analysis of the dinuclear complex, hexane molecules are incorporated into the cavities formed as the result of supramolecular packing. Coordination of a phosphine ligand makes dinuclear silver pyrazolate to exhibit blue emission at room temperature.     

High-Yield Syntheses of Sodium,Potassium, and Thallium Hydrotris[3,5-bis(trifluoromethyl)pyrazolyl]borates and the X-ray crystal structure of {hydrotris[3,5-bis(trifluoromethyl)pyrazolyl]borato} thallium(I)

An improved synthesis of 3,5-bis(trifluoromethyl)pyrazole ( 1 ) is described. This compound was used for the high-yield syntheses of the tris(pyrazoly1)borates Nd[HB(3,5-(CF₃),-pz)₃] ( 2a ) and the corresponding potassium salt, 2b , starting from 1 and NaBH₄ and KBH₄, respectively. A convenient route to the corresponding thallium(I) salt, 2c , using thallium(I) acetate and either 2a or 2b in CHCI₃, is also described. The sodium ( 3a ), potassium ( 3b ), and thallium ( 3c ) salts of bis(pyrazolyl)borate [H₂B(3,5-(CF₃)₂-pz)₂]^? were also prepared. The above pyrazolylborates were characterized by ¹H-, ¹³C-, ¹⁹F-, and ¹¹B-NMR spectroscopy. The X-ray crystal structure of the thallium derivative 2c was determined. The compound crystallizes in the monoclinic space group P2₁/m with a = 8.248(9) Å, b = 15.034(12) Å c = 9.243(8) Å, β = 100.10(7)°, Z = 2. The Tl-atom adopts a pyramidal geometry with respect to the three N-atoms. However, two TI–N distances (2.725(7) Å) are longer than the third (2.675(10) Å).     

On/off chemical determination of reactive amino groups immobilized on silica surfaces

Reaction of silica frameworks with aminosilanes to generate reactive amino groups on the surface of solid supports is a widely used step in the chemical modification of such surfaces. These reactive amino groups can aid in the chemical attachment ofproteins (enzymes and/or antibodies)_or chelating agents. Analytical accounting of the reactive groups generated is of interest in method optimization and in reactor design when these materials are used. A nondestructive method for the determination of reactive amino groups after attachment to silica surfaces is presented; it can be used for in-situ determinations in reactors. The method involves on/off chemistry based on the attachment of a chromophoric probe (p-dimethylaminoinnamaldehyde), its subsequent detachment under different experimental conditions, and spectrophotometric measurement of the released probe at 390 nm. Aspects of covalent attachment of amino groups to silica surfaces are also discussed.