Synthesis and antioxidant activities of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives

A series of 2-oxo-quinoline-3-carbaldehyde Schiff-base derivatives 4a₁–4n₂ were designed and synthesized based on the 2-oxo-quinoline structure core as novel antioxidants. In vitro antioxidant activities of these compounds were evaluated and compared with commercial antioxidants ascorbic acid, BHT and BHA, employing DPPH assay, ABTS⁺ assay, O₂^? assay and OH assay. The results showed that IC₅₀ of most compounds were lower than standard value 10 mg/mL, indicating good antioxidant activities of these compounds. In addition, in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 4b₂, 4e₁, 4e₂ and 4g₂, 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) cation (ABTS⁺) radical scavenging activities of compounds 4a₁, 4e₁, 4e₂, 4f₁, 4f₂, 4g₁, 4g₂, 4h₁, 4h₂, 4k₁, 4k₂, 4n₁ and 4n₂, superoxide anion radical scavenging activities of 4b₁, 4e₁, 4f₂, 4j₁, 4k₁, 4k₂, 4m₁, 4m₂, and 4n₂, and hydroxyl radical scavenging activity of almost all the compounds except 4f₁, 4f₂, 4j₂, 4l₁ and 4l₂ were better than that of the commercial antioxidant butylated hydroxytoluene (BHT).     

Syntheses,structures and photoluminescent property of coordination complexes with 2-(1H-1,2,4-triazol-1-yl)acetic acid

Reactions of ligand 2-(1H-1,2,4-triazol-1-yl)acetic acid (HL) with varied metal salts of Cu(II), Co(II), Ni(II), Zn(II), Cd(II) and Ag(I) result in formation of six new coordination complexes, {[Cu(L)₂] · 3H₂O}_n (1), [Co(L)₂(H₂O)₂]_n (2), [Ni(L)₂(H₂O)₂]_n (3), [Zn(L)₂(H₂O)₂]_n, (4), [Cd(L)₂]_n (5) and [Ag(L)]_n (6), and their structures were determined by X-ray crystallography. Complexes 1, 2, 3 and 4 with square-planar or octahedral metal centers have similar two-dimensional (2D) network structure with (4, 4) topology, while complex 5 displays a 2D structure with (6, 3)-connected topology. Complex 6 has a three-dimensional (3D) structure, in which the Ag(I) has tetrahedral coordination geometry. Ligand L^? acts as a 2-connected rod (bridging ligand) in 1, 2, 3 and 4, and acts as 3-connected nodes in 5 and 6. The results indicate that the coordination modes of the ligand and metal centers have great influence on the structures of the complexes. In addition, the photoluminescent properties of ligand HL and complexes 4 and 5 were studied in the solid state at room temperature.     

Interactions of platinum—1-methyluracil blue and its hydrolysis products with DNA

The preparation of Pt(NH₃)₂(MeU)₂·2H₂O, 1. [(NH₃)₂Pt(MeU)₂Pt(NH₃)₂](NO₃)₂, 2. Pt(NH₃)₂Cl(MeU), 3. and (in solution) [Pt(NH₃)₂(OH)(MeU)], 4. (MeU = 1-methyluracil monoanion) is reported. Levels of l-methyluracil and 1–4 in platinum-l-methyluracil blue (PtMeUB) have been assessed by high performance liquid chromatography (HPLC). This technique has also been used to show that in physiological saline or water, PtMeUB hydrolyzes to 3 or 4, respectively. Visible spectroscopy shows that the rate of hydrolysis of PtMeUB is much faster in fetal calf serum than in saline or water, with HPLC indicating that the product of hydrolysis in serum is 3. The precipitate obtained upon treatment of DNA solutions with PtMeUB has also been shown to hydrolyze to 3 or 4 when suspended in saline or water. Compounds 1–3 have been tested against the Ascites S-180J tumors, with 2 and 3 being active, while 4 has been shown to react readily with DNA. Possible mechanisms of antitumor action of PtMeUB that involve 3 and 4 are proposed.     

Synthesis and photochemical redox reactivity of an unsymmetrically substituted MnMn Bond: mer,fac-Mn2(CO)6(PMe2CH2PMe2)2

The reaction of Mn₂(CO)₁₀ with the diphosphine bis(dimethylphosphino)methane, dmpm, gives a mixture of two isomers: mer, fac-Mn₂(CO)₆(dmpm)₂, 1, and mer,mer-Mn₂(CO)₆(dmpm)₂, 2. Complex 1 is the first example of a bis(dmpm) complex with a cis,trans arrangement of the dmpm ligands. Both 1 and 2 can be thermally oxidized by one-electron to give the relatively stable binuclear radial cations [mer,fac-Mn₂(CO)₆(dmpm)₂]⁺, 3, and [mer,mer- Mn₂(CO)₆(dmpm)₂]⁺ , 4, respectively. The EPR spectra of 3 and 4 in THF indicate localization of unpaired spin density on one of the two Mn metal centers. The EPR of 4 in CH₂Cl₂ indicates delocalization of unpaired spin density over both Mn metal centers. The unsymmetrical isomer, 1, is a strong one-electron photoreductant. The excited state redox potential of 1, E° (3/1*), has been approximated to be −1.35 ⩽E° (3/1*)⩽−1.87 V vs. SCE. Under the same experimental conditions the symmetrical isomer 2 exhibits no photochemical redox behavior.     

Synthesis,characterization and in silico designing of diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxylate derivative as anti-proliferative and anti-microbial agents

A series of eight compounds diethyl-3-methyl-5-(6-methyl-2-thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxamido) thiophene-2,4-dicarboxilate (KM_10–17) analogues have been prepared by conventional methods and characterized by IR, Mass, NMR and elemental analysis. In silico docking studies on Human topoisomerase IIbeta (PDB Id: 3QX3) have been performed for all molecules (KM_10–17) synthesized. The compounds were tested for in vitro anti-proliferative activity on VERO and 786-O cell lines. Out of all the synthesized compounds, KM₁₁ & KM₁₆ showed moderate activity on both cell lines. In vitro anti-microbial activity was also checked against Bacillus subtilis (BS), Staphylococcus aurous (SA), Pseudomonas aeruginosa (PA), Escherichia coli (EC) and Candida albicans (CA) by well diffusion method. The compound KM₁₁ was found to have highest zone of inhibition against BS, SA, PA and EC. The molecules KM₁₃ and KM₁₆ exhibited good activity against CA. The compounds KM₁₄ and KM₁₆ indicated good zone of inhibition against BS.     

Synthesis,insecticidal activities and SAR of novel phthalamides targeting calcium channel

In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activities of title compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of title compounds showed moderate to high activities at the tested concentration. The structure–activity relationship (SAR) was discussed in detail. During synthesizing title compounds B₈, C₇, D₁, D₉ and D₁₂, their corresponding positional isomers (B₈′, C₇′, D₁′, D₉′ and D₁₂′) were afforded, and their structures were confirmed by 2D NMR. The calcium-imaging technique was also applied to investigate the effects of compounds B₂, B₁₀, C₄ and C₅ on the intracellular calcium ion concentration ([Ca²⁺]_i), which indicated that they released stored calcium ions from endoplasmic reticulum, which denoted that some compounds are potential modulators of the insect ryanodine receptor (RyR).     

Synthesis, structural characterization and in vitro cytotoxicity and anti-bacterial activity of some copper(I) complexes with N,N′-disubstituted thioureas

A series of copper(I) complexes of N,N′-disubstituted thioureas, [C₆H₅CONHCSNHR]Cu(I)Cl where R = C₆H₅ (1a), 2-ClC₆H₄ (2a), 3-ClC₆H₄ (3a), 4-ClC₆H₄ (4a), 2,3-Cl₂C₆H₃ (5a), 2,4-Cl₂C₆H₃ (6a), 2,5-Cl₂C₆H₃ (7a), 2,6-Cl₂C₆H₃ (8a), 3,4-Cl₂C₆H₃ (9a) and 3,5-Cl₂C₆H₃ (10a) have been synthesized. These complexes (1a–10a) have been characterized by elemental analyses, IR, ¹H and ¹³C NMR spectroscopy, cyclic voltammetry and single crystal XRD for 1a and 8a, and for ligand 7. The X-ray crystal structures reveal that the complexes 1a and 8a are mononuclear in the solid state in which the copper atoms adopt a distorted tetrahedral geometry. In both the cases, the neutral N,N′-disubstituted thiourea ligands have been coordinated to the Cu(I) through the sulphur atom in a terminal mode. The complexes have been screened for their in vitro cytotoxic activity in human cell lines carcinomas A498 (Renal), EVSA-T (Breast), H226 (Lung), IGROV (Ovarian), M19 (Melanoma-Skin), MCF-7 (Breast) and WIDR (Colon). They show a moderate cytotoxicity against these seven human cancer cell lines comparable to that of the less active standard chemotherapeutic drugs used for comparison. They were also screened for their anti-bacterial activity and were found less active than the standard drug Imipenem.     

Design,synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists

New series of phthalimide-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds 6_c, 6_d, 6_g, 6_h, 6_j and 6_k induced significant reduction in the blood glucose levels of diabetic rats ranging from 24.43 to 21.43%. Moreover, molecular docking and pharmacophore approaches were carried out to examine binding modes and fit values of the prepared compounds against PPARγ and SUR, respectively. Compounds 6_c, 6_d, 6_j and 6_m exhibited the highest binding free energies against PPARγ. Compounds 6_c, 6_j, 6_k, 6_l, and 6_n showed the highest fit values against the generated pharmacophore model. Also, QSAR technique was carried out to estimate the proposed PPARγ binding affinities and insulin-secreting abilities. The synthesized compounds showed promising estimated activities. In-silico ADMET studies were performed to investigate pharmacokinetics of the synthesized compounds. They showed considerable human intestinal absorption with low BBB penetration.     

Self-assembly of glutamic acid linked paclitaxel dimers into nanoparticles for chemotherapy

In this work, a glutamic acid linked paclitaxel (PTX) dimer (Glu-PTX₂) with high PTX content of 88.9 wt% was designed and synthesized. Glu-PTX₂ could self-assemble into nanoparticles (Glu-PTX₂ NPs) in aqueous solution to increase the water solubility of PTX. Glu-PTX₂ NPs were characterized by electron microscopy and dynamic light scattering, exhibiting spherical morphology and favorable structural stability in aqueous media. Glu-PTX₂ NPs could be internalized by cancer cells as revealed by confocal laser scanning microscopy and exert potent cytotoxicity. It is envisaged that Glu-PTX₂ NPs would be an alternative formulation for PTX, and such amino acid linked drug dimers could also be applied to other therapeutic agents.     

Synthesis and biological investigation of new equatorial (β) stereoisomers of 3-aminotropane arylamides with atypical antipsychotic profile

A series of novel 3β-aminotropane derivatives containing a 2-naphthalene or a 2-quinoline moiety was synthesised and evaluated for their affinity for 5-HT_1A, 5-HT_2A and D₂ receptors. Their affinity for the receptors was in the nanomolar to micromolar range. p-Substitution (6c, 6f, 6i, 6l, 6o), as well as substitution with chlorine atoms (6g, 6h, 6i), led to a significant increase in binding affinity for D₂ receptors with compounds 6f (K_i = 0.6 nM), 6c and 6i (K_i = 0.4 nM), having the highest binding affinities. m-Substituted derivatives were the most promising ligands in terms of 5-HT_2A receptor binding affinity whereas 2-quinoline derivatives (10a, 10b) displayed the highest affinity for 5-HT_1AR and were the most selective ligands with K_i = 62.7 nM and K_i = 30.5 nM, respectively. Finally, the selected ligands 6b, 6d, 6e, 6g, 6h, 6k, 6n and 6o, with triple binding activity for the D₂, 5-HT_1A and 5-HT_2A receptors, were subjected to in vivo tests, such as those for induced hypothermia, climbing behaviour and the head twitch response, in order to determine their pharmacological profile. The tested ligands presented neither agonist nor antagonist properties for the 5-HT_1A receptors in the induced hypothermia and lower lip retraction (LLR) tests. All tested compounds displayed antagonistic activity against 5-HT_2A, with 6n and 6o being the most active. Four (6b, 6k, 6n and 6o) out of eight tested compounds could be classified as D₂ antagonists. Additionally, evaluation of metabolic stability was performed for selected ligands, and introduction of halogen atoms into the benzene ring of 6h, 6k, 6n and 6o improved their metabolic stability. The project resulted in the selection of the lead compounds 6n and 6o, which had antipsychotic profiles, combining dopamine D₂-receptor and 5-HT_2A antagonism and metabolic stability.     

Novel 8-(furan-2-yl)-3-substituted thiazolo [5,4-e][1,2,4] triazolo[1,5-c] pyrimidine-2(3H)-thione derivatives as potential adenosine A2A receptor antagonists

Novel thiazolotriazolopyrimidine derivatives (23–33) designed as potential adenosine A_2A receptor (A_2AR) antagonists were synthesized. Molecular docking studies revealed that all compounds (23–33) exhibited strong interaction with A_2AR. The strong interaction of the compounds (23–33) with A_2AR in silico was confirmed by their high binding affinity with human A_2AR stably expressed in HEK293 cells using radioligand-binding assay. The compounds 24–26 demonstrated substantial binding affinity and selectivity for A_2AR as compared to SCH58261, a standard A_2AR antagonist. Decrease in A_2AR-coupled release of endogenous cAMP in treated HEK293 cells demonstrated in vitro A_2AR antagonist potential of the compounds 24–26. Attenuation in haloperidol-induced motor impairments (catalepsy and akinesia) in Swiss albino male mice pre-treated with compounds 24–26 further supports their role in the alleviation of PD symptoms.     

Synthesis of 3-aza[4.4.3]propellanes with high σ1 receptor affinity

In order to obtain rigid σ₁ receptor ligands with defined orientation of pharmacophoric elements, the azapropellane scaffold was chosen. Schmidt rearrangement of propellan-8-ones 6 and 10 provided 3-azapropellan-4-ones 7 and 11. Benzylation of the secondary lactams 7 and 11 followed by LiAlH₄ reduction furnished the azapropellanes 4a and 4c, respectively. A second hydrophobic element was introduced by transformation of the alcohols 4a into carbamates 4b. The σ₁ affinity of the azapropellanes 4 is strongly dependent on the stereochemistry and the substitution pattern in 12-position. anti-configured azapropellanes anti-4a and anti-4b show higher σ₁ affinity than their syn-configured counterparts syn-4a and syn-4b. Conversion of the alcohol anti-4a into the carbamate anti-4b led to increased σ₁ affinity, but complete removal of the 12-substituent resulted in the highest σ₁ affinity (K_i(4c)?=?17?nM). It can be concluded that the propellane scaffold alone is able to form strong lipophilic interactions and stabilize the ligand–σ₁ receptor complex as does usually the primary hydrophobic region.     

Synthesis and initial evaluation of novel,non-peptidic antagonists of the αv-integrins αvβ3 and αvβ5

The discovery, synthesis and preliminary SAR of a novel class of non-peptidic antagonists of the α_v-integrins α_vβ₃ and α_vβ₅ is described. High-throughput screening of an extensive series of ECLiPS? compound libraries led to the identification of compound 1 as a dual inhibitor of the α_v-integrins α_vβ₃ and α_vβ₅. Optimization of compound 1 involving, in part, introduction of two novel constraints led to the discovery of compounds 15a and 15b with reduced PSA and much improved potency for both the α_vβ₃ and α_vβ₅ integrins. Compounds 15a and 15b were shown to have promising activity in functional cellular assays and compound 15a also exhibited a promising Caco-2 permeability profile.     

Improvement of σ1 receptor affinity by late-stage C–H-bond arylation of spirocyclic lactones

The direct C–H-bond arylation of the complex spirocyclic lactones 13, 14, and 18 allows the introduction of diverse aryl moieties in the last step of the synthesis. A selective α-arylation of the thiophene moiety was performed with the catalytic system PdCl₂/2,2′-bipyridyl/Ag₂CO₃, whereas the β-position of the thiophene ring was addressed by using the alternative catalytic system PdCl₂/P[OCH(CF₃)₂]₃/Ag₂CO₃. Due to electronic and steric reasons the arylation of the five-membered lactone 18 occurred in both α-positions providing 4′-mono-, 6′-mono- and 4′,6′-diarylated thiophenes 22–26a–c. Compounds with an additional aryl moiety at the ‘upper left (top)’ position (1′-position of 13, 3′-position of 14, 4′-position of 18) showed increased σ₁ affinity compared to the non-arylated parent compounds. A phenyl moiety at the ‘left’ position (2′-position in 20a) also increased the σ₁ affinity but to a lower extent. A considerable reduction of σ₁ affinity was observed after introducing an aryl moiety in 6′-position of 18, which might result from shielding the tertiary amine, which is crucial for interaction with the σ₁ receptor. The discussion of the experimental results is supported by high-level quantum chemical DFT-calculations of the NBO-charges of 13 and 18 and the relative energies of the related arylated products.     

Reactions of CO2 with tetrahydroborato copper(I) complexes in moist solvents: Synthesis and reactions of [(phen)2Cu] [(HO)3B(O2CH)] and (phen)(Ph3P)Cu(O2COH) (phen = 1,10-phenanthroline)

Carbon dioxide reacts with the tetrahydroborato copper(I) complex, (phen)(Ph₃P)Cu(BH₄) (phen = 1,10-phenanthroline) (1) in moist tetrahydrofuran and in the presence of free phen affording the ionic derivative [(phen)₂Cu] [(HO)₃B(O₂CH)] (3). The same complex 3 can be obtained from 1 and aqueous formic acid in the presence of phen; from the new tetrahydroborato copper(I) complex, (phen)₂Cu(BH₄) (2), and aqueous formic acid; and from 2 with CO₂ in moist tetrahydrofuran.The reaction of (phen)(Ph₃P)Cu(BH₄) (1) with CO₂ in moist methanol gives the bicarbonato derivative, (phen)(Ph₃P)Cu(O₂COH) (4). The action of alcohols, ROH, on 3 causes the formation of the ionic formato complex [(phen)₂Cu](O₂CH) (5), the boron atom being eliminated as the alkyl boric ester, (RO)₃B. Complex 3 reacts with an alcoholic triphenylphosphine solution giving the already reported covalent formato derivative, (phen)(Ph₃P)Cu(O₂CH). The reaction of 3 with PhCH₂Br gives the benzyl formic ester HCO₂CH₂Ph. The reactivity of 4 toward neutral ligands such as phen and CyNC has been investigated, the ionic bicarbonato derivatives, [(phen)₂Cu](HCO₃) (8) and [(phen)(CyNC)₂Cu](HCO₃) (9), being obtained respectively.     

New pentafluorophenyl complexes with phosphine-amide ligands

A series of nickel(II) and palladium(II) complexes containing one or two pentafluorophenyl ligands and the phosphino-amides o-Ph₂PC₆H₄CONHR [R = ⁱPr (a), Ph (b)] displaying different coordination modes have been synthesised. The chelating ability of these ligands and the influence of both coligands and the metal centre in their potential hemilabile behaviour have been explored. The crystal structure of (b) has been determined and reveals N–H⋯O intermolecular hydrogen bonding. Bis-pentafluorophenyl derivatives [M(C₆F₅)₂(o-Ph₂PC₆H₄CO-NHR)] [M = Ni; R = ⁱPr (1a); R = Ph (1b); M = Pd; R = ⁱPr (2a); R = Ph (2b)] in which (a) and (b) act as rigid P, O-chelating ligands were readily prepared from the labile precursors cis-[M(C₆F₅)₂(PhCN)₂]. X-ray structures of (1a), (1b) and (2a) have been established, allowing an interesting comparative structural discussion. Dinuclear [{Pd(C₆F₅)(tht)(μ-Cl)}₂] reacted with (a) and (b) yielding the monopentafluorophenyl complexes [Pd(C₆F₅)Cl{PPh₂(C₆H₄–CONH–R)}] (R = ⁱPr (3a), Ph (3b)) that showed a P, O-chelating behaviour of the ligands, confirmed by the crystal structure determination of (3a). New cationic palladium(II) complexes in which (a) and (b) behave as P-monodentate ligands have been synthesised by reacting them with [{Pd(C₆F₅)(tht)(μ-Cl)}₂], stoichiometric Ag(O₃SCF₃) and external chelating reagents such as cod [Pd(C₆F₅)(cod){PPh₂(C₆H₄-CONH-R)}](O₃SCF₃)(R = ⁱPr (4a), Ph (4b)) and 2,2′-bipy [Pd(C₆F₅)(bipy){PPh₂(C₆H₄-CONH-R)}](O₃SCF₃) (R = ⁱPr (5a), Ph (5b)). When chloride abstraction in [{Pd(C₆F₅)(tht)(μ-Cl)}₂] is promoted by means of a dithioanionic salt as dimethyl dithiophospate in the presence of (a) or (b), the corresponding neutral complexes [Pd(C₆F₅){S(S)P(OMe)₂}{PPh₂(C₆H₄-CONH-R)}] (R = ⁱPr (6a), Ph (6b)) were obtained.     

New bifunctional antioxidant/σ1 agonist ligands: Preliminary chemico-physical and biological evaluation

We previously reported bifunctional sigma-1 (σ₁) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. σ₁ and σ₂ affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong σ₁ affinity, displayed improved σ₁ selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed σ₁ agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on σ₁ selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which σ₁ receptor dysfunction and oxidative stress are contemporarily involved.     

Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern

The cannabinoid CB₁/CB₂ receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than ～840-fold CB₁/CB₂ subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB₁-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21.     

Synthesis and reactions of [M(CO)4(Ph2PSiMe3)X] complexes (M = Mn,Re; X = Halogen)

The silylphosphine ligand Ph₂PSiMe₃ reacts readily with a slurry of [Re(CO)₅X] (X  Cl, Br) in polar and in non-polar solvents to yield soluble cis-[Re(CO)₄- (Ph₂PSiMe₃)X] (Ia, X  Cl;Ib, X  Br) via CO substitution. Compound I is readily hydrolyzed by water or silica gel to cis-[Re(CO)₄(Ph₂PH)X]. Compound Ib reacts with [Re(CO)₅Br] to yield [Re₂(CO)₈(μ-PPh₂)- (μ-Br)] (II), and with [Mn(CO)₅Br] to yield [MnRe- (CO)₈(μ-PPh₂)(μ-Br)] (III).The reaction of Ph₂PSiMe₃ with [Mn(CO)₅X] (X=Cl,Br,I) is highly dependent upon reaction conditions.In polar and in non-polar solvents, an excess of ligand gives mainly cis-[Mn(CO)₄(Ph₂PSiMe₃)X] (IVa, X  Cl;IVb, X  Br;IVc, X I). With ligand: [Mn(CO)₅X] reacting ratios in the range 0.5–1.0:1, the products from the three respective halomanganese complexes in THF were: (a) mainly [Mn₂(CO)₈(μ- PPh₂)(μ-Cl) (Va); (b) both [Mn(CO)₄(Ph₂PSiMe₃)Br] and [Mn₂(CO)₈(μ-PPh₂)(μ-Br)] (Vb); and (c) exclusively [Mn(CO)₄(Ph₂PSiMe₃)I]. The compounds IVa-c are stable in solution at ambient temperatures and are readily hydrolyzed by water or methanol to [Mn(CO)₄(Ph₂PH)X]. Compound IVb reacts at room temperature with [Mn(CO)₅Cl] to yield only [Mn₂- (CO)₈(μ-PPh₂)(μ-Br)] (Vb); compound IVc reacts in hot toluene with [Mn(CO)₅Cl] to yield mainly [Mn₂(CO)₈(μ-PPh₂)(μ-I)] (Vc), together with a small amount of the chloro-bridged analog.The dinuclear species II, III and Va-c appear to be formed mainly via an intermolecular elimination of Me₃SiX from the appropriate [M(CO)₄(Ph₂PSiMe₃)X] and metalpentacarbonylhalide (chloride or bromide) complexes.     

Rhodium aryloxide complexes containing terdentate nitrogen ligands, C-O bond formation, hydrogen bonding with phenol and oxidative addition reactions. Molecular structure of an Rh(III)-acetyl complex

The new rhodium(I) phenoxide complexes [Rh(OPh) (2,6-(CH=R²)₂C₅H₃N)] (R² = i-Pr(3), t-Bu(4)) containing strongly electrondonating N-N′-N ligands, have been prepared by a metathesis reaction of [RhCl(2,6-(CH=R²)₂C₅H₃N)] (R² = i-Pr (1), t-Bu (2)) with NaOPh. These rhodium(I) phenoxide complexes 3 and 4, which are very sensitive to O₂ but stable towards H₂O, give with phenol the adducts [Rh(OPh) (2,6-(CH=NR²)₂C₅H₃N)] · HOPh (R2 = i-Pr (5), t-Bu (6)), which contain strong O-HO hydrogen bonds. The hydrogen bonded phenol could not be extracted with diethyl ether, while no exchange of the hydrogen bonded phenol and the phenoxide ligand in 4 is observed on the NMR time scale. However, a small excess of phenol results in exchange of the hydrogen bonded phenol, the coordinated phenoxide ligand and free phenol on the NMR time scale. Reaction of 3 and 4 with p-nitrophenol afforded [Rh(OC₆H₄-(NO₂-4))(2,6-(CH=R²)₂C₅H₃N)] · HOPh (R² = i-Pr (7), t-Bu (8)) in which the formed phenol is hydrogen bonded to the Rh(I)-OC₆H₄-(NO₂-4) moiety. The O-HO bond is less strong than in 5 and 6, as the hydrogen bonded phenol could be removed by diethyl ether.Treatment of 3 with acetyl chloride and benzoyl chloride in benzene at room temperature gave phenylacetate and RhCl₂(C(O)C₆H₃) (2,6(C(H)=N-i-Pr)₂C₅H₃N)] (15), and phenylbenzoate and [RhCl₂(C(O)Ph) (2,6-(C(H)=N-i-Pr)₂C₅H₃N)] (19), respectively. Complex 15 and the analogous complex [RhCl₂(C(O)CH₃) (2,6-(C(H)=N-t-Bu)₂C₅H₃N)] (16) could also be prepared directly from acetyl chloride and 1 or 2, respectively. The single crystal X-ray determination of complex 16, monoclinic, space group P2₁/_c, a = 10.0477(5), b= 11.7268(6), c= 19.2336(9) Å, β = 92.041(4)°, Z = 4, R₁ = 0.0281, shows that the acetyl group occupies an axial position, while the N-N′-N ligand is positioned equatorially. In solution this geometry remains unchanged as was shown by variable temperature ¹H NMR measurements. When the oxidative addition of acetyl chloride to 3 was carried out at −78°C in toluene the intermediate complex [RhCl(OPh) (C(O)Me) (2,6-(C(H)=N-i-Pr)₂C₅H₃N)] (11) could be isolated, which at room temperature reductively eliminates phenylacetate with formation of 1. Oxidative addition of acetyl chlori de to 4 at room temperature gives [RhCl(OPh) (C(O)Me) (2,6-(C(H)=Nt-Bu)₂C₅H₃N)] (12) which yields phenylacetate and 2 at 70°C in benzene by inductive elimination. Treatment of 3 with two equivalents of benzyl chloride afforded a mixture of [RhCl(OPh) (CH₂Ph) (2,6-(C(H)=N-i-Pr)₂C₅H₃N)] (13) and [RhCl₂(CH₂Ph) (2,6-(C(H)=N-i-Pr)₂C₅H₃N)] (17) and some non-characterizable organic products, while 4 only yielded [RhCl(OPh) (CH₂Ph) (2,6-(C(H)=N-tBu)₂C₅H₃N)] (14).