Chloro Precursor Research Articles

A Terminal Hydride of Hafnium Supported by a Triamidoamine Ligand

A mononuclear hafnium hydride supported by an aryl-substituted triamidoamine ligand [HfH(thf)(Xy-N3N)] (Xy-N3N = {(3,5-Me2C6H3)NCH2CH2}3N3–) was synthesized by either hydrogenolysis of the hydrocarbyl complex [Hf(R)(thf)(Xy-N3N)] (R = Me, CH2SiMe3, η3-C3H5, CH2Ph) in tetrahydrofuran (THF) or, more conveniently, by salt metathesis of the chloro precursor [HfCl(thf)(Xy-N3N)] with NaBEt3H in methylcyclohexane. The structure of a terminal hydride with a distorted capped trigonal bipyramidal geometry was characterized by single crystal X-ray diffraction (d(Hf–H): 1.83(3) Å) and by 1H NMR spectroscopy. The unusually low field shifted 1H chemical shift for the hydride ligand was detected at δ 18.28 ppm. Dehydrogenative thermolysis of the hydride complex at 25 °C in benzene or toluene resulted in deprotonation of the α-hydrogen of one of the three XyNCH2CH2 groups in the ligand by the hydride, followed by the combination of this deprotonated anionic complex with cationic complex [Hf(Xy-N3N)]+ to give an unsymmetric dinuclear complex bridged by μ-H, μ-NXy, and μ,κN,κC-XyNCHCH2 groups. This decomposition product was characterized by single crystal X-ray diffraction and by 1H and 13C NMR spectroscopy and analyzed by density functional theory (DFT) calculations. Hydrogenation in THF at 25 °C reformed the hydride complex over a period of 48 h. The hydride complex reacted with olefins RHC═CH2 (R = H, Et, nHex, cHex, Ph) to give the corresponding anti-Markovnikov insertion products [Hf(CH2CH2R)(thf)n(Xy-N3N)]. Catalytic hydrogenation of olefins was achieved with 5 mol % of the hydride complex at 70 °C in THF or benzene.

Photolability of NO in ruthenium nitrosyls with pentadentate ligand induces exceptional cytotoxicity towards VCaP, 22Rv1 and A549 cancer cells under therapeutic condition

Pentadentate electron rich MePBITA ligand in [RuII(MePBITA)(NO)]n+ (n = 3, 2 and MePBITA = 1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) permits the isolation of both the redox states of nitrosyls with Enemark–Feltham notation {RuNO}6 and {RuNO}7. The nitrosyl derivative [RuII(MePBITA)(NO)](ClO4)3: [4](ClO4)3 was synthesized by stepwise synthetic manner from the chloro precursor [RuII(MePBITA)(Cl)](PF6): [1](PF6), via the acetonitrile derivative [RuII(MePBITA)(CH3CN)](PF6)2: [2](PF6)2 followed by nitro complex [RuII(MePBITA)(NO2)](PF6): [3](PF6). All the complexes were fully characterized by different analytical and spectroscopic techniques. Single crystal X-ray structures of the complexes [1](PF6), [2](PF6)2, [3](PF6), and [4](ClO4)3 were profitably determined for understanding the molecular integrity. Ru−NO stretching frequency observed at 1931 cm−1 for [4](ClO4)3 suggests a moderately electrophilic character of NO. The huge shift in νNO frequency, Δν (solid) = 325 cm−1 was observed by reducing [4](ClO4)3 to [4](ClO4)2. The conversion of [3]+ from [4]3+ was examined both electrochemically and spectrophotometrically with the addition of 0.5 M NaOH solution. Rate constants of the first order photorelease (kNO) have been found to be 8.99 × 10−3 min−1; half-life (t1/2) = 77 min and 3.84 × 10−2 min−1; half-life (t1/2) = 18 min for [4]3+ and [4]2+, respectively with visible Xenon light (200 W) source. The photo liberated NO has been scavenged by biologically relevant target protein reduced myoglobin as Mb−NO adduct. Photoactivation of [4]3+ and [4]2+ by visible light induces significant cytotoxicity in prostate cancer cell lines; VCaP (IC50 29.74 and 4.42 µM) and 22Rv1 (IC50 29.96 and 6.88 µM), and lung cancer cell line; A549 (IC50 2.24 and 0.12 µM). Collectively our results pave the way for the development of metallodrugs as potential therapeutics for a variety of cancers. Additionally, our results also demonstrate how ligand modification could enhance the photolability of metal nitrosyl, adding a new dimension for future efficient photoactive metal nitrosyl design.

The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C inhibitors.

As part of a medicinal chemistry program aimed at developing a highly potent and selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled materials were required. The synthesis of tritium-labeled methanesulfonate 5 was achieved via catalytic tritiolysis of a chloro precursor, albeit at a low radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and stable isotope-labeled AZD5248 were successfully prepared through modifications of the medicinal chemistry synthetic route, enabling the use of available labeled intermediates.

Exploring the Intricacies of Weak Interactions in Metal-Metal Bonds Using an Unsymmetrical Carbonyl Precursor and a Triple-Bonded W2(6+) Paddlewheel.

Stepwise reaction of W(CO)6 with tetramethylated bicyclic guanidinate ligands, characterized by a central C(N)3 unit joining two fused six-membered rings with CH2CMe2CH2 units spanning two of the nitrogen atoms, allowed isolation of W2(μ-CO)2(μ-TMhpp)2(η(2)-TMhpp)2, 1, a precursor of W2(TMhpp)4Cl2 ( J. Am. Chem. Soc. 2013 , 135 , 17889 ; TMhpp = [(CH2CMe2CH2)2(C(N)3)]). Subsequent heating of 1 followed by reaction with TlPF6 generates [W2(TMhpp)4](PF6)2, 2. Compound 1 has an edge-sharing bioctahedral (ESBO) arrangement with a W2(μ-CO)2(4+) core having semibridging carbonyl groups, while 2 has a paddlewheel structure with a W2(6+) core spanned by four tetramethyl-substituted bicyclic guanidinate ligands. This compound also has hexafluorophosphate anions along the metal-metal bond that are nestled within methylene groups with the aid of a network of weak C-H···F interactions that prevent a close approach of the fluorine atoms to the dimetal unit. Theoretical computations were carried out on ditungsten model complexes supported by three ligand sets: bicyclic guanidinate, guanidinate, and formamidinate. The computations show that the π-accepting ability of the carbonyl groups significantly lowers the energy of the σ* orbital, and thus, the energy falls below that of the δ orbital. This information along with the diamagnetism of both 1 and 2-as shown by the sharp signals in the (1)H NMR spectra that support a lack of unpaired electrons (S = 0)-is consistent with the electronic configuration of σ(2)π(2)σ*(2)δ(2) (π(2)δ(2)) and thus a formal bond order of 2 for 1 and σ(2)π(4) for the triple-bonded W2(6+) core in 2. A comparison of the W-W bond lengths in 2, its chloro precursor W2(TMhpp)4Cl2, and the corresponding analogue W2(hpp)4Cl2 shows a substantial effect from the axially coordinated ligand, distal lone pair in determining the length of the metal-metal bond for these paddlewheel species. The importance of the ligands in tuning the energy level of the metal-metal bonds that may lead to dramatic changes in physical properties is also discussed. It is noteworthy that bicyclic guanidinates with the strongest π-donating ability push upward the energy level of the δ orbital, thus allowing the compounds to be easily oxidized.

Diastereoselective Attack on Chiral-at-Metal Ruthenium Allenylidene Complexes To Give Alkynyl Complexes

New chiral ruthenium(II) allenylidene complexes were synthesized, and their reactivity with nucleophiles to give alkynyl complexes was investigated. The new allenylidene complex (RRu,Rax)-[Ru(Ind)(PPh3)(6){═C═C═C(t-Bu)(2-naphthyl)}]+PF6– was synthesized from the chloro precursor complex (RRu,Rax)-[RuCl(Ind)(PPh3)(6)] and the racemic propargylic alcohol HC≡CC(OH)(t-Bu)(2-naphthyl) and obtained in 96% yield, where (Rax)-6 is a chiral phosphoramidite and Ind an anionic indenyl ligand. The precursor and the allenylidene complex are chiral-at-metal, and the chiral information is completely transferred from the chloro precursor to the product allenylidene complex, both of which show the same absolute configuration, as demonstrated by X-ray diffraction. Together with the known allenylidene complex (RRu,Rax)-[Ru(Ind)(PPh3)(6)(═C═C═CPh2)]+PF6–, the attack of n-BuLi, MeLi, LiC≡CPh, and lithium 1-phenylethenolate nucleophiles on the allenylidene chain of (RRu,Rax)-[Ru(Ind)(PPh3)(6){═C═C═C(t-Bu)(2-naphthyl)}]+PF6– wa...

Luminescent Alkynylplatinum(II) Complexes of 2,6‐Bis(N‐alkylbenzimidazol‐2′‐yl)pyridine‐Type Ligands with Ready Tunability of the Nature of the Emissive States by Solvent and Electronic Property Modulation

A new class of luminescent alkynylplatinum(II) complexes of tridentate bis(N-alkylbenzimidazol-2'-yl)pyridines (bzimpy), [Pt(R,R'-bzimpy)(C[triple chemical bond]C-R'')]X (X=PF(6), OTf), and one of their chloro precursor complexes, [Pt(R,R'-bzimpy)Cl]PF(6), have been synthesized and characterized; one of the alkynyl complexes has also been structurally characterized by X-ray crystallography. Electrochemical studies showed that the oxidation wave is alkynyl ligand-based in nature with some mixing of the metal center-based contribution, whereas the two quasi-reversible reduction couples are mainly bzimpy-based reductions. The electronic absorption and luminescence properties of the complexes have also been investigated. In solution, the high-energy and intense absorption bands are assigned as the pi-pi* intraligand (IL) transitions of the bzimpy and alkynyl ligands, whereas the low-energy and moderately intense absorptions are assigned to an admixture of metal-to-ligand charge-transfer (MLCT) (dpi(Pt)-->pi*(R,R'-bzimpy)) and ligand-to-ligand charge-transfer (LLCT) (pi(C[triple chemical bond]C-R'')-->pi*(R,R'-bzimpy)) transitions. Upon variation of the electronic effects of the arylalkynyl ligands, vibronic-structured or structureless emission bands, originating from triplet metal-perturbed intraligand (IL) or an admixture of triplet metal-to-ligand charge-transfer (MLCT) and ligand-to-ligand charge-transfer (LLCT) excited states respectively, were observed in solution. Interestingly, two of the complexes showed a dual luminescence that was sensitive to the polarity of the solvents. Upon cooling from 298 K to 155 K, drastic color, UV/Vis, and luminescence changes were observed in a butyronitrile solution of 1, and were ascribed to the formation of aggregate species through PtPt and pi-pi stacking interactions. DFT and time-dependent DFT (TD-DFT) calculations have been performed to verify and elucidate the results of the electrochemical and photophysical properties.

The first structural study on a cyclic tricoordinate phosphorochloridite and a pentacoordinate phosphorane based on 1,2,3,5-protected myo-inositol—a new conformation of 1,3,2-dioxaphosphorinane ring

Treatment of the phosphoramidite { myo-C 6H 6-2-[OC(O)Ph]-1,3,5-(O 3CH)-4,6-(O 2P-NH- i-Pr)} with o-chloranil affords the first example of inositol-based pentacoordinate phosphorane { myo-C 6H 6-2-[OC(O)Ph]-1,3,5-(O 3CH)-4,6-(O 2P-NH- i-Pr)(1,2-O 2C 6Cl 4)} ( 9) (X-ray structure) with a trigonal bipyramidal geometry at phosphorus. The six-membered 1,3,2-dioxaphosphorinane ring with the inositol residue has an unusual boat conformation in 9 which is quite different from that found in unrestrained rings investigated before, but is similar to that of its P III chloro precursor { myo-C 6H 6-2-[OC(O)Ph]-1,3,5-(O 3CH)-4,6-(O 2PCl)} (X-ray structure). Also, a convenient and chromatography-free procedure for the protected myo-inositol derivative { myo-C 6H 6-2-[OC(O)Ph]-1,3,5-(O 3CH)-4,6-(OH) 2} is reported.

Ruthenium hydride complexes of chiral and achiral diphosphazane ligands and asymmetric transfer hydrogenation reactions

The half-sandwhich ruthenium chloro complexes bearing chelated diphosphazane ligands, [(η 5-Cp)RuCl{κ 2-P,P-(RO) 2PN(Me)P(OR) 2}] [R = C 6H 3Me 2-2,6] ( 1) and [(η 5-Cp ∗)RuCl{κ 2-P,P-X 2PN(R)PYY′}] [R = Me, X = Y = Y′ = OC 6H 5 ( 2); R = CHMe 2, X 2 = C 20H 12O 2, Y = Y′ = OC 6H 5 ( 3) or OC 6H 4 t Bu-4 ( 4)] have been prepared by the reaction of CpRu(PPh 3) 2Cl with (RO) 2PN(Me)P(OR) 2 [R = C 6H 3Me 2-2,6 ( L 1)] or by the reaction of [Cp ∗RuCl 2] n with X 2PN(R)PYY′ in the presence of zinc dust. Among the four diastereomers (two enantiomeric pairs) possible for the “chiral at metal” complexes 3 and 4, only two diastereomers (one enantiomeric pair) are formed in these reactions. The complexes 1, 2, 4 and [(η 5-Cp)RuCl{κ 2-P,P-Ph 2PN(( S)- ∗CHMePh)PPhY}] [Y = Ph ( 5) or N 2C 3HMe 2-3,5 ( S C S P R Ru)-( 6)] react with NaOMe to give the corresponding hydride complexes [(η 5-Cp)RuH{κ 2-P,P-(RO) 2PN(Me)P(OR) 2}] ( 7), [(η 5-Cp ∗)RuH{κ 2-P,P′-X 2PN(R)PY 2}] [R = Me, X = Y = OC 6H 5 ( 8); R = CHMe 2, X 2 = C 20H 12O 2, Y = OC 6H 4 t Bu-4 ( 9)] and [(η 5-Cp)RuH{κ 2-P,P-Ph 2PN(( S)- ∗CHMePh)PPhY}][Y = Ph ( 10) or N 2C 3HMe 2-3,5 ( S C S P R Ru)-( 11a) and ( S C S P S Ru)-( 11b)]. Only one enantiomeric pair of the hydride 9 is obtained from the chloro precursor 4 that bears sterically bulky substituents at the phosphorus centers. On the other hand, the optically pure trichiral complex 6 that bears sterically less bulky substituents at the phosphorus gives a mixture of two diastereomers ( 11a and 11b). Protonation of complex 7 using different acids (HX) gives a mixture of [(η 5-Cp)Ru(η 2-H 2){κ 2-P,P-(RO) 2PN(Me)P(OR) 2}]X ( 12a) and [(η 5-Cp)Ru(H) 2{κ 2-P,P-(RO) 2PN(Me)P(OR) 2}]X ( 12b) of which 12a is the major product independent of the acid used; the dihydrogen nature of 12a is established by T 1 measurements and also by synthesizing the deuteride analogue 7-D followed by protonation to obtain the D–H isotopomer. Preliminary investigations on asymmetric transfer hydrogenation of 2-acetonaphthone in the presence of a series of chiral diphosphazane ligands show that diphosphazanes in which the phosphorus centers are strong π-acceptor in character and bear sterically bulky substituents impart moderate levels of enantioselectivity. Attempts to identify the hydride intermediate involved in the asymmetric transfer hydrogenation by a model reaction suggests that a complex of the type, [Ru(H)(Cl){κ 2-P,P-X 2PN(R)PY 2}(solvent) 2] could be the active species in this transformation.

Synthesis of 6-[18F]fluoroveratraldehyde by nucleophilic halogen exchange at electron-rich precursors

Fluorodehalogenation reactions were used to prepare 6-[18F]fluoroveratraldehyde. The synthesis of 6-[18F]fluoroveratraldehyde is the first step in the multi-step synthesis of the clinically important tracer 6-[18F]fluoro-L-dopa. In the literature yields ranging from 20-50% are reported when using nitro and trimethylammoniumtriflate precursors. However, no data exist concerning the use of different leaving groups such as halogens. Therefore, 6-bromo, 6-chloro and 6-fluoroveratraldehyde were tested in the nucleophilic aromatic substitution by [18F]fluoride. In DMF, 6-[18F]fluoroveratraldehyde was obtained with radiochemical yields of (57±1.0)% and (66±3.6)% in 20 minutes at 160 °C using 50 mg/ml bromo and chloro precursor, respectively. The fluoro precursor gave a radiochemical yield of (87±0.8)% at 140 °C. Temperature, solvent and concentration strongly affected the 18F-labeling. Among the halogens the ability as a leaving group was F>>Cl>Br. The halogenated veratraldehydes provide a good alternative for the synthesis of ca and nca 6-[18F]fluoroveratraldehyde, as the first step of the synthesis for [18F]FDOPA since they are inexpensive, commercially available, stable, sustain hard conditions in the labeling step, and give yields better or equal to other precursors previously reported.

Unexpected isolation and structural characterization of a redox-active Fe(II) piano-stool complex with an η 1-dppe ligand

A new cationic complex [(η 2-bipy)(η 5-C 5Me 5)Fe(η 1-dppe)][BPh 4] featuring a pendant free diphenylphosphine arm has been isolated in good yield after reaction of 2,2′-bipyridine with the known chloro precursor complex (η 2-dppe)(η 5-C 5Me 5)FeCl in presence of NaBPh 4. This complex which can be envisioned as a new redox-active building-block has been structurally characterized.

Probing the polymer-electrode interface using neutron reflection

We demonstrate that neutron reflection (NR) can be used to characterize polymer films deposited on indium tin oxide (ITO). When the chloro precursor to poly[2-(2′-ethylhexyloxy)5-methoxy-1,4-phenylenevinylene] (MEHPPV) was spin-coated onto ITO NR revealed that between the ITO and the uniform polymer layer was a 20 Å thick low contact zone. We found that the conversion of the chloro precursor to MEHPPV at 180 °C under vacuum gave a uniform film of MEHPPV with the layer of low contact between the polymer and ITO remaining. Finally, the NR profile suggests that the blueshift in the MEHPPV absorption spectrum on ITO when compared to quartz is due to polymer morphology and not incomplete conversion.

Neutron reflection study on soluble and insoluble poly[2-(2’-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene) films

Neutron reflection (NR) has been utilized to study the physical structure of the light-emitting polymer poly[2-(2’-ethylhexyloxy)-5-methoxy-1,4-phenylenevinylene) (MEHPPV). Films of soluble MEHPPV (S-MEHPPV) and insoluble MEHPPV (I-MEHPPV) prepared via a chloro precursor polymer were investigated. For S-MEHPPV spin-coated films were found to contain two layers, one of low-density and thickness of ≈1360 Å with the second layer being thinner, ≈240 Å, but denser. The thicker layer only covered about 30% of the substrate surface. In contrast, I-MEHPPV formed uniform films across the substrate. We found that during the thermal conversion of the chloro precursor polymer the film thickness was maintained and it was only on cooling that the films contracted. Importantly, the thermal expansion and contraction of I-MEHPPV was reversible. NR showed that thermal annealing of I-MEHPPV had little affect on the films physical structure while for S-MEHPPV only the thinner layer was changed and became more dense. Photoluminescence spectra of S-MEHPPV before and after annealing showed that the densification observed in the neutron reflection measurements was mirrored in the emission properties of the polymer film.

Control of conjugation in poly(arylenevinylene)s

Poly(1,4-phenylenevinylene) (PPV) and derivatives have been studied extensively for use in polymer based LEDs. It has been shown that the introduction of low levels of saturated units into the polymer backbone can give LEDs with improved efficiency. We have developed a new route to partially conjugated PPV derivatives enabling the final polymer to be formed with ethylene links bearing no leaving groups. This was achieved by the treatment of the chloro precursor to poly{2-(2'-ethyl)hexyloxy-5-methoxy-1,4-phenylenevinylene} (MEHPPV) with different amounts of tri-n-butyltin hydride to form copolymers which contain selected proportions of unsubstituted and chlorine substituted ethylene linkages. The subsequent thermal conversion gave rise to conjugated copolymers containing ethylene and vinylene linkages.

Control of polymer–electrode interactions: the effect of leaving group on the optical properties and device characteristics of EHPPV

Poly[2-(2′-ethylhexyloxy)-1,4-phenylenevinylene] (EHPPV) was prepared via chloro, S-methyl xanthate and O-ethyl xanthate precursor polymers. The choice of leaving group used was found to control the optical and device properties of the EHPPV with the variations arising from the differing chemical interactions of the leaving groups with indium tin oxide (ITO). The leaving group–ITO interactions were found to dominate the properties of EHPPV when formed from the commonly used chloro precursor polymer and this problem could be solved by use of xanthate leaving groups which were found not to react with the contact.

Comparison of precursor polymer routes to and electronic properties of a new phenylacetylene derivatised poly[2-(2′-ethylhexyloxy)-1,4-phenylenevinylene

We have prepared poly[2-(2′-ethylhexyloxy)-5-phenylethynyl-1,4-phenylenevinylene] (PAPPV) 13via, S-methyl xanthate 10, chloro 11, and O-ethyl xanthate 12 precursor polymers. All three precursor polymers could be thermally converted to give films of 13. We found that the UV–VIS and photoluminescence (PL) spectra, and PL quantum yields (11–14%) were similar when 13 was prepared from either the S-methyl xanthate or chloro precursor polymers. In contrast, the UV–VIS and PL spectra of 13 prepared via the O-ethyl xanthate precursor polymer were observed to be blue-shifted and the PL quantum yield was much lower (2%).

Comparison of the electronic properties of poly[2-(2′-ethylhexyloxy)-1,4-phenylenevinylene] prepared by different precursor polymer routes

S. Lo, A. K. Sheridan, I. D. W. Samuel and P. L. Burn, J. Mater. Chem., 1999, 9, 2165 DOI: 10.1039/A902602I

Synthetic, spectroscopic, and structural Studies on Lanthanide Complexes of Diphosphazane Dioxide Ligands

AbstractLanthanide nitrate complexes of diphosphazane dioxides Ph2P(O)N(Pri)P(O)Ph2 (1) and (PhO)2P(O)N(Me)P(O)(OPh)2 (2) have been synthesised and studied by conductometry, IR, multinuclear NMR spectroscopic methods and X‐ray diffraction. Ligand 2 is accessible by two different methods, viz., by direct oxidation of the phosp(III)azane ligand or by starting from phosph(V)azane chloro precursor. The structure of 2 is confirmed by X‐ray diffraction. Crystallographic data for 2: Triclinic, Space group P1, a = 10.078(1), b = 10.575(3), c = 12.364(4) Å, α = 75.70(2)°, α = 75.56(1)°, γ = 77.68(1)°, Z = 2, V = 1 220 Å3; structure refined to RF = 0.0459 on 3 495 data with F > 3σ(F). The diphosphazane dioxide ligand exhibits trans geometry in the solid state. The structure of a lanthanide complex, [Pr(NO3)3(2)2] (14) is also determined by X‐ray diffraction. Crystallographic data for 14: Trigonal, Space group P32, a = b = 15.710(2), c = 40.067(2) Å, Z = 6, V = 8 564 Å3; structure refined to RF = 0.0430 on 8 077 data with F > 5σ(F). The two diphosphazane dioxide ligands and the nitrate groups are coordinated to praseodymium in a bidentate chelate fashion. The geometry around the ten coordinated metal is distorted bicapped square antiprism.

An Improved Purification Method for the Rapid Synthesis of High Purity Fluorobutyrophenone Neuroleptics from Nitro and Chloro Precursors Suitable for PET Study

Abstract A rapid micro-scale synthesis of fluorinated neuroleptics with extremely high chemical purity was accomplished using a new single column reverse-phase HPLC purification procedure that employs a strongly alkaline eluent to clearly separate F-labeled compounds from the large excess of nitro or chloro precursor. The method is applicable to the production of 18F-labeled positron emission tomography (PET) tracers with high specific activity.