Cyclometallation ofN,N-dimethyl-3-furancarbothioamide with palladium(II), platinum(II), ruthenium(II) and rhodium(III)

Summary N, N-Dimethyl-3-furancarbothioamide (Hbft) was cyclometallated with Li₂PdCl₄, K₂PtCl₄, RuCl₂(CO)₃, and RhCl (PBu₃)₂ (PBu₃=tri-n-butylphosphine) to give, respectively, PdCl(bft), PtCl(bft), RuCl(bft)(CO)₂, and RhCl₂ (bft)(PBu₃)₂. These and some of their derivatives were characterized spectroscopically. Cyclometallation occurs regioselectively at position 2 of the furan ring to give a five-membered metallaheterocycle, along with Secoordination of the thioamide group. When the position 2 of the furan ring is blocked by a methyl group,N, N-dimethyl-2-methyl-3-furancarbothioamide (Hmft) is, in similar conditions, cyclopalladated at the N–Me substituout of the thioamide group, the furan ring being left intact. Position 4 of the furan ring of both Hbft and Hmft is unreactive toward cyclometallation.     

Cyclometallation of 2-(2-thienyl)pyridine and 2-(3-thienyl)pyridine with palladium(II), rhodium(III) and ruthenium(II)

Summary 2-(2-Thienyl)pyridine [H(2-tp)] and 2-(3-thienyl)pyridine [H(3-tp)] react with lithium tetrachloropalladate(II), hexachlorotetrakis(tri-n-butylphosphine) dirhodium(III), and tetrachlorohexacarbonyldiruthenium(II) to give [PdCl(C-N)]₂-(CN=2-tp and 3-tp), [RhCl₂(C-N)PBu₃]₂ (C-N = 2-tp and 3-tp), and [RuCl(2-tp)(CO)₂]₂, respectively. Some bromo analogues are also prepared. These complexes react with pyridine and tri-n-butylphosphine to give adducts in which 2-tp is chelated through pyridine-N and thiophene-3-C and 3-tp through pyridine-N and thiophene-2-C atoms. The structures of these complexes are similar to those of the corresponding complexes of cyclometallated 2-phenylpyridine.     

Cyclopalladation of N,N,N′,N′-tetramethylisophthalthioamide

Summary N,N,N,N-Tetramethylisophthalthioamide (Hmpt) was cyclopalladated with PdCl₂ in hot dimethylsulphoxide to give [PdCl(mpt)]. The structure was determined by X-ray analysis. The thioamide is metallated at C(2) to act as an S528-01C528-02S tridentate anionic ligand. There is appreciable steric repulsion between the benzene ring H(4, 6) and the dimethylamino groups. The hydrogens and the methyl groups mutually deviate from the coordination plane in opposite directions. The stability of the fused 5,5-membered chelate ring formed by the S528-03C528-04S ligand seems to overcome the steric hindrance. Derivatives were prepared by replacement of the chloride ion with iodide, diethyldithiocarbamate, 4-tert-butylpyridine, or tri-n-butylphosphine, and characterized spectroscopically. The S528-05C528-06S-fused chelate ring was maintained in these derivatives.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Effect of acidity on chelate ring closure occurring by chloro,nitro or azido group displacement in rhodium(III) complexes

The effect of CH₃COOH, ClCH₂COOH, Cl₂CHCOOH, Cl₃CCOOH and of ClCH₂COOH-ClCH₂COO^? buffers on the rates of the conversion of mer-[Rh(L)(L′)Cl₂X] into trans-[Rh(L)₂Cl₂]⁺ + X^? has been investigated in methanol [L and L′ = (o-dimethylaminophenyl)dimethylarsine-NAs and -As, respectively; X^? = Cl^?, NO₂^?, N₃^?. The rates have been found to depend only on the hydrogen ion concentration and not on the particular concentration or strength of the acid used. The observed rate constant of mer-[Rh(L)(L′)Cl₃] is decreased by increasing the hydrogen ion concentration. Conversely, k_obs for mer-[Rh(L)(L′)Cl₂N₃] increases smoothly up to a maximum limiting value by increasing the hydrogen ion concentration. A similar behaviour is shown by mer-[Rh(L)(L′)Cl₂NO₂], but in this case the rate constant achieves a maximum value and then it decreases towards a limiting value as the hydrogen ion concentration is increased further. The dependence of k_obs on [H⁺] for the acid-dependent reaction path of the mer → trans conversion of mer-[Rh(L)(L′)Cl₃] and mer-[Rh(L)(L′)Cl₂N₃] is explained in terms of protonation at the - NMe₂ free end of L′, whereas also diprotonation of the complex is tentatively invoked to explain the kinetic effect of acidity on the reactions of mer-[Rh(L)(L′)Cl₂NO₂].     

Synthesis of cyclopalladated 2-(1-pyrrolyl)pyrimidine derivatives

Summary 2-(1-Pyrrolyl)pyrimidine(Hprpm) is cyclopalladated with lithium tetrachloropalladate in methanol in the presence of sodium acetate to give PdCl(prpm). This complex reacts with dimethylsulfoxide(dmso), pyridine(py). tri-n-butylphosphine(PBu₃), tri-p-tolylphosphine(Ptol₃), triphenylarsine(AsPh₃), and acetylacetone(Hacac) to give PdCl(prpm)L (L=dmso, py, PBu₃, Ptol₃, AsPh₃) and Pd(prpm)(acac), respectively. These complexes were characterized spectroscopically. The deprotonated ligand, prpm, is cyclopalladated and coordinated through pyrimidine-N and pyrrole-2C atoms to form a five membered palladaheterocycle.     

The reaction of indole and the indole grignard reagent with phosgene. A facile synthesis of indole-3-carboxylic acid derivatives

Indole-3-carboxylic acid (as well as indole-3-glyoxylic acid) derivatives are readily prepared from indoles (including oxindoles) and phosgene (oxalyl chloride), respectively. The interaction of these reagents with the indole Grignard reagent afforded several products including the cyclo-tetramers, 21 and 30 . Indolo-fused heterocycles can be readily prepared from the reaction of phosgene (or oxalyl chloride) with suitable reactants. Thus e.g., phosgene and 2-(2-hydroxy-phenyl)-N-methylindole readily gave 5,6-dihydro-11-methyl-6-oxobenzo[a]pyrano[4,3-b] indole ( 33 ).     

Syntheses,characterization, and crystal structures of ruthenium(II)/(III) complexes with tridentate salicylaldiminato ligands

Treatment of [Ru(PPh₃)₃Cl₂] with one equivalent of tridentate Schiff base 2-[(2-dimethylamino-ethylimino)-methyl]-phenol (HL) in the presence of triethylamine afforded a ruthenium(III) complex [RuCl₃(κ²-N,N-NH₂CH₂CH₂NMe₂)(PPh₃)] as a result of decomposition of HL. Interaction of HL and one equivalent of [RuHCl(CO)(PPh₃)₃], [Ru(CO)₂Cl₂] or [Ru(tht)₄Cl₂] (tht = tetrahydrothiophene) under different conditions led to isolation of the corresponding ruthenium(II) complexes [RuCl(κ³-N,N,O-L)(CO)(PPh₃)] (2), [RuCl(κ³-N,N,O-L)(CO)₂] (3), and a ruthenium(III) complex [RuCl₂(κ³-N,N,O-L)(tht)] (4), respectively. Molecular structures of 1·CH₂Cl₂, 2·CH₂Cl₂, 3 and 4 have been determined by single-crystal X-ray diffraction.     

Synthesis of 3H[1,2]diazepino[5,6-b]indole and 3H[1,2]diazepino[4,5-b]indole derivatives

The synthesis of two new derivatives of 3H[1,2]diazepino[5,6-b]indole, 5 and 11 , and one new derivative of 3H[1,2]diazepino[4,5-b]indole, 16 , are described. Compound 5 was obtained by the reaction of methyl 2-(3-methoxycarbonyl-1-methylindole)acetate 2 , with hydrazine. Compound 11 was obtained in two ways from ethyl 2-(1-methylindole)acetate ( 8 ) by formylation and reaction with hydrazine. Compound 16 was obtained treating 3-(2-ethoxycarbonylindole)acetonitrile ( 14 ) with hydrazine.     

Metal-induced soluble bending structure of polyazomethine having a tetradentate ligand in the main chain

Polymer 3 having a tetradentate Schiff's base derivative of β-diketone was prepared by polycondensation of a bis(β-diketone) monomer ( 1 ) with 1,2-diaminocyclohexane ( 2 ). A polymer metal chelate in which all coordination sites of 3 were occupied with copper(II) ions was obtained. The polymer chelate was soluble in CHCl₃, CH₂Cl₂, N,N-dimethylformamide, and tetrahydrofuran. Gel-permeation chromatography measurements showed that the complex formation with copper(II) ions induced changes in the conformation of 3 in solution.     

EXCIPLEX STUDIES–V. ELECTRON EJECTION FROM INDOLE AND METHYL-INDOLE DERIVATIVES*

Abstract— Electron-scavenging experiments with N₂O as scavenger demonstrate at least two electron-producing reactions of the excited singlet states of the exciplex species formed by indole or 1 -methyl-indole with water. Most electrons reacting with N₂O result from collision of the scavenger with a metastable state formed from the initial exciplex state but finite electron yields from indole and 1-methyl-indole at limiting scavenger concentrations suggest that the intermediate states also eject electrons directly into the solvent. The formation of the first metastable state from the fluorescent exciplex state has an activation energy, E_M, estimated to be about 13 kcal/mole for both indole and 1 -methyl-indole water exciplexes. The E_M values for 1-methyl-indole from fluorescence and electron yields are the same, Indicating that at neutral and alkaline pH fluorescence quenching and electron extraction are both being controlled by the formation of the first metastable intermediate. Observed electron yields from indole-water and indole-methanol exciplexes are less than predicted using fluorescence data, although E_M values of 1 kcal/mole are obtained for the indole-methanol exciplex by both methods. At pH 12·0 and 28°C the total electron yields for indole-water and 1 -methyl-indole-water exciplexes are 0·30 and 0·25, respectively. The residual yields attributed to outright formation of hydrated electrons from the initial exciplex excited stateare 0·11 and 0·05, respectively. Electron yields from the indole-water exciplex are strongly pH dependent only near pH 1 where the fluorescence yields as well as the electron yields decrease rapidly with increasing acidity. The 1-methyl-indole-water exciplex shows an additional pH dependence which is first-order in hydrogen-ion activity and has an effective pK_a of about 11·5. Comparable yields for indole and 1-methyl-indole are found only above pH 12. High electron yields are found with indole in the exciplex-forming solvent dioxane and in the non-exciplex forming solvent cyclohexane. For the latter system electrons are probably derived only from the lowest excited state of indole on collision with N₂O.     

Rhodium(I) carbonyl complexes with sulphur and nitrogen donor ligands

Summary Rhodium(I) carbonyl complexes, namely [Rh(CO)₂ClL] where L = thiourea (Tu), 1,3-diphenyl-2-thiourea (DTu), dithizone (Dtz), indole (Id), 3-chloropyridine (Clpy), 3-hydroxypyridine (HOpy), 3-methylpyridine (Mepy), 2,5-dimethylpyridine (Me₂py) or 2,5-dichloropyridine (Cl₂py)] were prepared. [Rh(CO)₂Cl(Clpy)₂] has also been isolated. In the (Tu) complex, (C-S) occurs at ca. 710cm^-1, indicating the presence of a metal-sulphur bond. The carbonyl stretching frequencies in [Rh (CO)₂ClL] and [Rh(CO)₂CIL₂] occur at ca. 2100–1990 and 1830–1800 cm^-1, respectively. PPh₃ reacts with the complexes to form trans-[Rh(CO)Cl(PPh₃)₂]. The complexes were characterized by elemental analyses, conductivity measurements and by their i.r. spectra.     

Study of hydroformylation of formaldehyde in the presence of rhodium catalysts byin situ IR spectroscopy and the kinetic technique

Carbonylrhodium complexes formed during hydroformylation of CH₂O from various rhodium precursors were investigated byin situ IR spectroscopy. It was found that under the conditions of the hydroformylation of CH₂O inN,N-dimethylacetamide (DMAA), RhH(CO)(PPh₃)₃, RhCl(CO)(PPh₃)₂, RhCl(PPh₃)₃, RhCl(CO)(PBu₃)₂, and [RhCl(CO)₂]₂ form complex systems that necessarily contain anionic complexes, [Rh(CO)₂L_x(DMAA)_y]^– (L = PPh₃, PBu₃,x = 1 to 2,y = 1 to 0; [Rh(CO)₄]^–). The participation of ionic structures in the hydroformylation of CH₂O, most likely, in the step of the activation of CH₂O, was proven by kinetic techniques.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1066–1069, June, 1995.     

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and indolyl-substituted titanocene anti-cancer drugs

Abstract From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different ortho-lithiated indole derivatives (5-methoxy-N-methylindole, N-methylindole and N,N-dimethylaminomethylindole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl₄ resulting in dimethylamino-functionalised titanocenes (5a–c). When these titanocenes were tested against LLC-PK cells, the IC₅₀ values obtained were of 37 and 71 μM for titanocenes 5a and 5b respectively. The most cytotoxic titanocene in this paper, 5c showed an IC₅₀ value of 8.4 μM is found to be almost as cytotoxic as cis-platin, which showed an IC₅₀ value of 3.3 μM, when tested on the LLC-PK cell line, and titanocene 5c is approximately 250 times better than titanocene dichloride itself. Graphical Abstract Bis-(N,N-dimethylamino-2-(N-methylindolyl)methylcyclopentadienyl) titanium (IV) dichloride was synthesised starting from 2-(N-methylindolyl) lithium and 6-N,N-dimethylamino fulvene. Herein, we present the synthesis and DFT structure of the titanocene and two further derivatives followed by MTT-based cytotoxicity tests on LLC-PK cells.      

Strained Ruthenium Complexes Bearing Tridentate Guanidine-Derived Ligands

The dimer [{(η⁶-p-cymene)RuCl}₂(μ-Cl)₂] (cymene=MeC₆H₄ⁱPr) reacts with N,N′-bis(p-tolyl)-N′′-(2-pyridinylmethyl)guanidine ( H₂L1 ) and N,N′-bis(p-tolyl)-N′′-(2-diphenylphosphanoethyl)guanidine ( H₂L2 ), in the presence of NaSbF₆, giving rise to chlorido compounds of formula [(η⁶-p-cymene)RuCl( H₂L )][SbF₆] ( H₂L = H₂L1 ( 1 ), H₂L2 ( 2 )) in which the guanidine ligand adopts a κ² chelate coordination mode. The related ligand (S)-N,N′-bis(p-tolyl)-N′′-(1-isopropyl, 2-diphenylphosphano ethyl)guanidine ( H₂L3 ) affords mixtures of the corresponding chlorido compound [(η⁶-p-cymene)RuCl( H₂L3 )][SbF₆] ( 3 ) together with the complexes [(η⁶-p-cymene)RuCl₂( H₃L3 )][SbF₆] ( 4 ) and [(η⁶-p-cymene)Ru(κ³N,N′,P- HL3 )][SbF₆] ( 10 ) which contain phosphano-guanidinium and phosphano-guanidinate ions acting as monodentate and tridentate ligand, respectively. Compounds 1 , 2 and mixture of 3 / 4 / 10 react with AgSbF₆ rendering the cationic aqua-complexes [(η⁶-p-cymene)Ru( H₂L )(OH₂)][SbF₆]₂ ( H₂L = H₂L1 ( 5 ), H₂L2 ( 6 ), H₂L3 ( 7 )). These aqua-complexes exhibit a temperature-dependent fluxional process in solution. Experimental NMR studies and DFT theoretical calculations on complex 6 suggest that the process involves the exchange between two rotamers around one of the C−N guanidine bonds. Treatment of 5 – 7 with NaHCO₃ renders the complexes [(η⁶-p-cymene)Ru(κ³N,N′,N′′- HL1 )][SbF₆] ( 8 ) and [(η⁶-p-cymene)Ru(κ³N,N′,P- HL )][SbF₆] ( HL = HL2 ( 9 ), HL3 ( 10 )), respectively, in which the HL ligand adopts a fac κ³ coordination mode. The new complexes have been characterized by analytical and spectroscopic means, including the determination of the crystal structures of the compounds 1 , 2 , 5 , 9 and 10 , by X-ray diffractometric methods.     

Synthesis of (3RS)- and (3SR)-acetoxy-(3aRS,8bSR)-N-acetyl-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles

Stereoisomeric 3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles differing by the configuration of the C³ atom were synthesized. The reaction of N-acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline with 50% hydrogen peroxide in the presence of Na₂WO₄-H₃PO₄ in AcOH gave (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was converted into the corresponding 3-O-acetyl derivative by treatment with acetic anhydride in pyridine. N-Acetyl-6-(cyclopent-2-en-1-yl)-2-methoxyaniline reacted with iodine in methylene chloride in the presence of NaHCO₃ to produce (3SR,3aRS,8bSR)-3-acetoxy-5-methoxy-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole which was subjected to acetylation at the nitrogen atom by reaction with acetic anhydride. The structure of (3RS,3aRS,8bSR)-N-acetyl-3-hydroxy-5-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was proved by X-ray analysis. Original Russian Text ? N.A. Likhacheva, A.A. Korlyukov, R.R. Gataullin, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 3, pp. 406–409.     

1-β-D-呋喃核糖基-1,2,4-三唑-3-酰胺铂配合物的合成研究

cis-[Pt(DMSO)₂Cl₂], K[Pt(DMSO)Cl₃]分别与两摩尔1-β-D-呋喃核糖基-1,2,4-三唑-3-酰胺(Ribavirin)进行络合反应, 制得了高收率的二配位铂配合物; 讨论了不同摩尔的1-β-D-呋喃核糖基-1,2,4-三唑-3-酰胺与cis-[Pt(DMSO)₂Cl₂]和K[Pt(DMSO)Cl₃]进行络合反应的结果; 对[Pt (N⁴,N⁷-Ribavirin)(DMSO)Cl]配合物(1)的X衍射晶体结构进行了测定.     

Complexing behaviour ofN-phenylcarbamoylpyrrole-2-thiocarboxamide

Summary The complexes Pd(PTH)₂Cl₂ · 3.5 H₂O, Pd(PTH)₃(PPh₃), Ru(PTH)₂(PPh₃)Cl₂, Ru(PTH)₂(PPh₃)Cl₃, Rh(PTH)₂(PPh₃)Cl and Rh(PT)Cl₂ · 0.5 H₂O, where PTH isN-phenylcarbamoylpyrrole-2-thiocarboxamide, have been prepared and characterised by magnetic and spectral (i.r., u.v. and visible) studies.     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

Activity of some platinum(II/IV) complexes with edda-type ligands against human adenocarcinoma HeLa cells

Cisplatin analogues, cis-dichloro(ethylenediamine-N,N′-di-3-propanoic acid)platinum(II) (1) and cis-iodo(ethylenediamine-N,N′-di-3-propanoic acid)platinum(II) (2), as well as trans-dichloro-(ethylenediamine-N,N′-di-3-propanoato)platinum(IV) (3), trans-dibromo(ethylenediamine -N,N′-di-3-propanoato)platinum(IV) (4), trans-dichloro(propylenediamine-N,N′-diacetato)-platinum(IV) (5) and trans-dibromo(propylenediamine-N,N′-diacetato)platinum(IV) (6), -([Pt(H₂eddp)Cl₂], [Pt(Heddp)I], trans-[Pt(eddp)Cl₂], trans-[Pt(eddp)Br₂], trans-[Pt(pdda)Cl₂] and trans-[Pt(pdda)Br₂], respectively) were used to assess antitumor selectivity against human adenocarcinoma HeLa cells. The results show that different oxidation states of platinum, different halide ligands, chelating aminocarboxylato and diamine backbones have similar effects with edda-type ligands and activity is lower than for cisplatin.