The mannich reaction in the synthesis of N,S-containing heterocycles 4. Aminomethylation of 6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates: A convenient regioselective route to 3,5,7,11-tetraazatricyclo[7.3.1.02,7]tridec-2-ene derivatives

Treatment of N-methylmorpholinium 4-R-6-amino-3,5-dicyano-1,4-dihydropyridine-2-thiolates (R = 2-ClC₆H₄ and 2-MeOC₆H₄) with primary amines in the presence of an excess of formaldehyde gave 13-R-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile derivatives in high yields (66–95%). In a similar way, aminomethylation of 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates (R = Me and Et) afforded 1′-alkyl-8-thioxospiro[3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-13,4′-piperidine]-1,9-dicarbonitriles in 43–91% yields. Alternatively, these compounds were obtained by multicomponent cyclocondensation of N-alkylpiperidin-4-ones, cyanothioacetamide, primary amines, and aqueous formaldehyde. The starting 3-R-10-amino-7,11-dicyano-9-aza-3-azoniaspiro[5.5]undeca-7,10-diene-8-thiolates were prepared by a new method from N-alkylpiperidin-4-ones and cyanothioacetamide. The structure of 5,11-bis(4-ethoxyphenyl)-13-(2-methoxyphenyl)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was examined by X-ray diffraction analysis. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1014–1022, May, 2007.     

Synthesis of 3-substituted cyclopenta[b]indoles

When reacting with I₂, 2-(cyclopent-2-enyl)anilines undergo cyclization into 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in high yields. The minor reaction products were 3,5- or 3,7-diiodoindolines. Ammonolysis of 3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydro-cyclopenta[b]indole or itsN-chloroacetyl derivative results in 3-amino-5-methyl-1,2,3,3a,48b-hexahydro- and 5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles. Published inIzvestiya Akademii Nauk. Seriya Khimischeskaya, No. 10, pp. 1789–1793, October, 2000.     

Deoxypegan-1-one derivatives. synthesis and borohydride reduction of 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones

3-[(E)-Arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones were prepared by reaction of quinazolyl-2-propionic acid hydrochloride with aromatic aldehydes in acetic anhydride in the presence of Et₃N. 3-[(E)-Arylmethylidene]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-ols were formed by reduction of the 3-arylidene derivatives with sodium borohydride in methanol, readily lost water when heated with acids, and were converted into 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolines. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 463–467, September–October, 2006.     

Regioselective Heterocyclization of 3-(Cyclohex-2′-enyl)-4-hydroxy-6-methylpyran-2-one

Summary.  Regioselective heterocyclization of 3-(cyclohex-2′-enyl)-4-hydroxy-6-methyl pyran-2-one with various reagents afforded different heterocycles. With N-iodosuccinimide in acetonitrile at 0–5°C it gave 6-methyl-9′-iodo-2′-oxabicyclo[3.3.1]nonano[3,2-c]pyran-2-one, with C₅H₅NHBr₃ or C₆H₁₂N₄HBr₃ in CHCl₃ at 0–5°C it furnished 6-methyl-9′-bromo-2′-oxabicyclo[3.3.1]nonano[3,2-c]pyran-2-one. Cold concentrated H₂SO₄ lead to 6-methyl-2′-oxabicyclo[3.3.1]nonano[3,2-c]pyran-2-one, whereas PdCl₂(PhCN)₂ in C₆H₆ at 80°C afforded 9-methyl benzofuro[3,2-c]pyran-2-one. Corresponding author. E-mail: kcm@klyuniv.ernet.in Received December 27, 2001. Accepted (revised) March 1, 2002     

Oxidative and hydrolytic cleavage of cyclopropane and spirocyclobutane derivatives of 6,8-dioxabicyclo[3.2.1]octane,the products of transformation of levoglucosenone

A new method for the synthesis of (1R,4S,5S)-4-hydroxymethyl-3-oxabicyclo[3.1.0]hexan2-one, the cyclopropane analog of (S)-5-hydroxypent-2-en-4-olide, has been suggested based on oxidation of (1S,2S,4R,6R)-7,9-dioxatricyclo[4.2.1.0^2,4]nonan-5-one. Oxidation of cyclobutanones, spirojoined with the fragments of 6,8-dioxabicyclo[3.2.1]oct-2-ene, 6,8-dioxabicyclo[3.2.1]octane (at position 4), or 7,9-dioxatricyclo[4.2.1.0^2,4]nonane (at position 5), upon the action of m-chloroperoxybenzoic acid or the KMnO₄-H₂SO₄-H₂O system leads to the corresponding spirojoined butanolides in 73–85% yields. The same cyclobutanones easily undergo the four-membered ring opening upon the action of dilute H₂SO₄ at 50–90 °C to form 6,8-dioxabicyclo[3.2.1]octane-4- or 7,9-dioxatricyclo[4.2.1.0^2,4]nonane-5-propionic acid.     

Syntheses,molecular structures and magnetic properties of two hybrid organic–inorganic salts of bis(maleonitriledithiolato)copper(II) and substituted benzyl-4-dimethylaminopyridinium cations

Two new hybrid organic–inorganic salts, [BzDMAP]₂[Cu(mnt)₂](1) and [NO₂BzDMAP]₂[Cu(mnt)₂] (2) ([BzDMAP]⁺ = 1-benzyl-4′-dimethylaminopyridinium, [NO₂BzDMAP]⁺ = 1-(4′-nitrobenzyl)-4′-dimethylaminopyridinium, and mnt²⁻ = maleonitriledithiolate) have been characterized structurally and magnetically. The [BzDMAP]⁺ or [NO₂BzDMAP]⁺ cations (C) and the [Cu(mnt)₂]²⁻ anions (A) in 1 and 2 stack into a 1D alternating CC-A-CC-A-CC column. The Cu···N, π···π, C–H···N, C–H···O, and C–H···S weak interactions play important roles in the molecular stacking and generate a 2D or 3D structure of 1 and 2. The magnetic susceptibilities of these salts measured in the temperature range 2.0–300 K show weak antiferromagnetic coupling features with θ = −2.370 K for 1 and −0.222 K for 2.     

Mononuclear and binuclear tricarbonylchromium complexes of aryl-substituted [2.2]paracyclophanes

The complexation reactions of monoaryl- and diaryl-substituted [2.2]paracyclophanes with (NH₃)₃Cr(CO)₃ have been studied. The aromatic rings of [2.2]paracyclophane are more favorable for coordination than aryl substituents. This leads to the regioselective formation of the corresponding mono- or binuclear tricarbonylchromium complexes. In some cases, the tricarbonylchromium group is coordinated to the aryl ring of the substituent to form (in low yields) the corresponding mononuclear complex or binuclear complexes with both the aromatic ring of paracyclophane and the aryl ring of the substituent involved in coordination. The structure of such complex, namely, [4-(η⁶-2,4,6-trimethylpheny)-11-16-η⁶-[2,2]paracyclophane]bis[tricarbonylchromium(0)] was confirmed by X-ray diffraction study. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 142–150, January, 1998.     

Synthesis, structural characterization and thermal properties of three copper(II) complexes based on aryl hydrazide ligands

The thiosemicarbazide and hydrazide Cu(II) complexes, [Cu₃L₂¹(py)₄Cl₂] (1), [Cu(HL²)py] (2) and [Cu(HL³)py] (3), (H₂L¹ = 1-picolinoylthiosemicarbazide, H₃L² = N′-(2-hydroxybenzylidene)-3-hydroxy-2-naphthohydrazide, H₃L³ = 2-hydroxy-N′-((2-hydroxy-naphthalen-1-yl)methylene)benzohydrazide) have been prepared and characterized through physicochemical and spectroscopic methods as well as X-ray crystallography. Complex 1 has a centrosymmetric structure with –N–N– bridged Cu₃ skeleton. Neighboring molecules are linked into a 3D supermolecular framework by π–π stacking interactions, N–H···Cl and C–H···Cl hydrogen bonds. Complexes 2 and 3 have similar planar structures but different dimers formed by concomitant Cu···N and Cu···O interactions, respectively. Solvent accessible voids with a volume of 391 ?³ are included in the structure of complex 2, indicating that this complex is a potential host candidate. Thermogravimetric analysis shows that the three complexes are stable up to 100 °C.     

2-(5-Benzoacridine)ethyl-p-toluenesulfonate as sensitive reagent for the determination of bile acids by HPLC with fluorescence detection and online atmospheric chemical ionization-mass spectrometric identification

2-(5-Benzoacridine)ethyl-p-toluenesulfonate (BAETS), a dual-sensitive probe, was reacted with bile acids in the presence of K₂CO₃ catalyst in dimethyl sulfoxide (DMSO) solvent to give BAETS–bile acid derivatives. Derivatives exhibited intense fluorescence (FL) with an excitation maximum at λ _ex 270 nm and an emission maximum at λ _em 510 nm. MS analysis using APCI-MS indicated that derivatives had excellent APCI-MS ionizability with percentage ionization δ values changing from 0 to 88.83% in aqueous acetonitrile and from 0 to 89.15% in aqueous methanol. The collision induced dissociation spectra of m/z [M + H]⁺ contained specific fragment ions at m/z [M + H−H₂O]⁺, [M + H−2H₂O]⁺, [M + H−3H₂O]⁺, 347.3, and 290.1. Repeatability was good for LC separation of BAETS–bile acid derivatives with aqueous acetonitrile as mobile phase. The relative standard deviations (RSDs) of retention time and peak area at 6.6 nmol mL⁻¹ levels with fluorescence detection (FL) were from 0.045 to 0.072% and from 2.16 to 2.73%, respectively. Excellent linear responses were observed, with regression coefficients >0.9995. The FL detection limits (S/N = 3) were in the range of 18.0–36.1 fmol. The online APCI-MS detection limits are in the range of 500–790 fmol (at a signal-to-noise ratio of 3).     

Synthesis, in vitro and in vivo behavior of 188Re(I)-tricarbonyl complexes for the future functionalization of biomolecules

Radiolabeling of biologically active molecules with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ unit has been of primary interest in recent years. Therefore, we herein report ligands L¹−L⁴ (L¹=histidine, L²=nitrilotriacetic acid, L³=2-picolylamine-N,N-diacetic acid, L⁴=bis(2-pyridymethy)amine) that have been evaluated by radiochemical reactions with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺. These reactions yielded the radioactive complexes of fac-[¹⁸⁸Re(CO)₃L] (L = L¹−L⁴, ¹⁸⁸Re tricarbonyl complexes 1–4), which were identified by HPLC. Complexes 1–4, with log P _o/w values ranging from −2.23 to 2.18, were obtained with yields of ≥95% using ligand concentrations within 10⁻⁶–10⁻⁴M range. Thus, specific activities of 220 GBq/μmol could be achieved. Challenge studies with cysteine and histidine revealed high stability for all of these radioactive complexes, and biodistribution studies in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion occurring primarily through the renal-urinary pathway. In summary, the ligands L¹–L⁴ are potent chelators for the future functionalization of biomolecules labeling with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺.     

An efficient and regioselective synthesis of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] from 4-alkoxy-1,1,1-trihaloalk-3-en-2-ones

Abstract  

This work describes the regioselective synthesis of two new series of 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-4,5-dihydro-5-hydroxy-5-(trihalomethyl)-1H-pyrazoles], where the 3-substituents are H, Me, C₆H₅, 4-FC₆H₄, 4-ClC₆H₄, 4-BrC₆H₄, 4-NO₂C₆H₄, 4,4′-BiPh, and 2-furyl, in a one-pot methodology with ethanol as solvent, from the reaction of 4-alkoxy-4-(alkyl/aryl/heteroaryl)-1,1,1-trihaloalk-3-en-2-ones with oxalyldihydrazide (51–89%). Complementarily, the dehydration reactions of five examples of the described oxalylbispyrazolines are also reported, which furnished the respective 1,1′-oxalylbis[3-(alkyl/aryl/heteroaryl)-5-(trihalomethyl)-1H-pyrazoles] in 53–78% yields without the two C(O)–N bond cleavages.     

Preparation of 4,4a,9,9a-tetrahydrocarbazoles and 1,3a,4,8b-tetra-hydrocyclopenta[b]indoles

Halocyclization of mesylates or tosylates of 2-(cycloalk-2-en-1-yl)anilines gives N-methanesulfonyl-or N-toluenesulfonyl-1-halo-1,2,3,4,4a,9a-hexahydrocarbazoles, heating of which in DMF at 160°C or in piperidine at 110°C leads to 4,4a,9,9a-tetrahydro-3H-carbazoles. Heating N-methanesulfonyl-1-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole in DMF at 180—200°C gives 1,3a,4,9b-tetrahydrocyclopenta[b]indole, while in the presence of an ortho-methyl substituent the dehydroiodination reaction proceeds in piperidine at 110°C in high yield. The effect of the nature of the ortho substituent of N-methyl-1-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole on the conformational equilibrium of the cyclopentane ring has been established by ¹H NMR spectroscopy. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1184–1190, August, 2006.     

Sulfanilamide copper(II) chelates with 2-[(2-hydroxyphenyl-imino)methyl]phenolom and 1-[(2-hydroxyphenylimino)-methyl]naphthalen-2-ol

2-[(2-Hydroxyphenylimino)methyl]phenol (H²L¹) and 1-[(2-hydroxyphenylimino)methyl]naphthalen-2-ol (H²L²) reacted with copper(II) acetate hydrate and sulfanilamide (Sf¹), sulfathiazole (Sf²), sulfaethidole (Sf³), sulfadiazine (Sf⁴), and sulfadimidine (Sf⁵) in ethanol to give mixed-ligand copper chelates with the composition Cu(Sf^1–5)(L^1–2) · n H₂O (n = 1, 2). All these complexes are monomeric. Salicylaldehyde imines (H₂L¹ and H₂L²) behave as doubly deprotonated tridentate O,N,O ligands, whereas sulfanilamides (Sf^1–5) are unidentate ligands. Thermolysis of the synthesized complexes includes dehydration at 70–90°C, followed by complete thermal decomposition (290–380°C). The complexes [Cu(Sf¹)(L¹)] · 2H₂O and [Cu(Sf³)(L¹)] · H₂O at a concentration of 10⁻⁴ M inhibited growth and reproduction of 100% of human myeloid leukemia cells (HL-60). The inhibitory effect was 90 and 75%, respectively, at a concentration of 10⁻⁵ M, whereas no antitumor activity was observed at a concentration of 10⁻⁶ M.     

An Efficient Mannich-Type One-Pot Synthesis of 3,5,7,11-Tetraazatricyclo [7.3.1.02,7]tridec-2-ene Derivatives Starting from Functionalized 1,4-Dihydropyridines

3,5,7,11-Tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene derivatives were prepared in one-pot manner from N-methylmorpholinium 6-amino-3,5-dicyano-4-spiro(1′-cycloalkane)-1,4-dihydropyridine-2-thiolates, primary amines, and formaldehyde in 70–88% yields. The structure of 5,11-dibenzyl-13-spiro(1′-cyclopentane)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was determined by X-ray diffraction analysis.     

Transformations of phosphazane ligands in the coordination sphere of transition metals. Reactions of phosphinotriazene Ph<Subscript>2</Subscript>P-N(Ph)-N=NPh with Ni<Superscript>0</Superscript> and Ni<Superscript>I</Superscript> complexes

3-(Diphenylphosphino)-1,3-diphenyltriazene Ph₂P-NPh-N=NPh was synthesized. The reactions of this compound with bis(cycloocta-1,5-diene)nickel, (cod)₂Ni, and nickel(I) bis(triphenylphosphino)bis(trimethylsilyl)amide, (Ph₃P)₂Ni-N(SiMe₃)₂, afforded the anionic nickel complex [Ph₄P]⁺[Ni(PhNNNPh)₃]⁻ in 15 and 78% yields, respectively. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1585–1589, July, 2005.     

An Efficient <Emphasis Type="Italic">Mannich</Emphasis>-Type One-Pot Synthesis of 3,5,7,11-Tetraazatricyclo [7.3.1.0<Superscript>2,7</Superscript>]tridec-2-ene Derivatives Starting from Functionalized 1,4-Dihydropyridines

Summary. 3,5,7,11-Tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene derivatives were prepared in one-pot manner from N-methylmorpholinium 6-amino-3,5-dicyano-4-spiro(1′-cycloalkane)-1,4-dihydropyridine-2-thiolates, primary amines, and formaldehyde in 70–88% yields. The structure of 5,11-dibenzyl-13-spiro(1′-cyclopentane)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was determined by X-ray diffraction analysis.     

Novel C<Subscript>β</Subscript>–C<Subscript>γ</Subscript> Bond Cleavages of Tryptophan-Containing Peptide Radical Cations

In this study, we observed unprecedented cleavages of the C_β–C_γ bonds of tryptophan residue side chains in a series of hydrogen-deficient tryptophan-containing peptide radical cations (M^•+) during low-energy collision-induced dissociation (CID). We used CID experiments and theoretical density functional theory (DFT) calculations to study the mechanism of this bond cleavage, which forms [M – 116]⁺ ions. The formation of an α-carbon radical intermediate at the tryptophan residue for the subsequent C_β–C_γ bond cleavage is analogous to that occurring at leucine residues, producing the same product ions; this hypothesis was supported by the identical product ion spectra of [LGGGH – 43]⁺ and [WGGGH – 116]⁺, obtained from the CID of [LGGGH]^•+ and [WGGGH]^•+, respectively. Elimination of the neutral 116-Da radical requires inevitable dehydrogenation of the indole nitrogen atom, leaving the radical centered formally on the indole nitrogen atom ([Ind]^•-2), in agreement with the CID data for [WGGGH]^•+ and [W_1-CH3GGGH]^•+; replacing the tryptophan residue with a 1-methyltryptophan residue results in a change of the base peak from that arising from a neutral radical loss (116 Da) to that arising from a molecule loss (131 Da), both originating from C_β–C_γ bond cleavage. Hydrogen atom transfer or proton transfer to the γ-carbon atom of the tryptophan residue weakens the C_β–C_γ bond and, therefore, decreases the dissociation energy barrier dramatically.     

The effect of the oxidative properties of [Mg(H2O)6] in the triplet and singlet states on the energetics of adenosine triphosphate cleavage

The interaction of the adenosine triphosphate (ATP) molecule (the ATP subsystem) with the magnesium complex [Mg(H₂O)₆]²⁺ (the Mg subsystem) in the singlet (S) and triplet (T) states in an aqueous medium mimicked by 78 water molecules was studied by the molecular dynamics (density functional theory) method MD DFT:B3LYP with the 6–31G** basis set at T = 310 K. Potential energy surfaces for the S (lowest-lying) and T (highest-lying) states are significantly separated in space. The Mg complex moves along these surfaces to approach either oxygen atoms of the γ-β phosphate groups (O1–O2) (S PES) or oxygen atoms of β-α phosphate groups (O2–O3) (T PES). Chelation of the γ-β β-α and phosphates yields, respectively, a stable low-energy complex ([Mg(H₂O)₄-(O1–O2)ATP]²⁻) and a metastable high-energy complex ([Mg(H₂O)₂-(O2–O3)ATP]²⁻), which differ in the number of water molecules surrounding the Mg atom. Crossing of two triplet PESs is accompanied by the formation of an unstable state characterized by redistribution of spins between the Mg and ATP subsystems. This state, sensitive to interaction with the ²⁵Mg nuclear spin, induces an unpaired electron spin, which initiates the ATP cleavage by the ion-radical mechanism, yielding a reactive radical ion of adenosine monophosphate (•AMP⁻), which was earlier found experimentally by the of chemically induced dynamic nuclear polarization (CIDNP) method. Biological aspects of the results obtained are discussed. Original Russian Text ? A.A. Tulub, V.E. Stefanov, 2009, published in Zhurnal Neorganicheskoi Khimii, 2009, Vol. 54, No. 7, pp. 1188–1195.     

Inhibition of J-aggregation of meso-tetra(4-sulfonatophenyl)porphyrin by an ionic liquid with π-conjugated character

Abstract  

UV–visible spectral observations indicate that the J-aggregation of protonated meso-tetra(4-sulfonatophenyl)porphyrin ([H₂TSPP]²⁺) under acidic conditions is completely inhibited by the π–π counteraction between 1-butyl-pyridinium tetrafluoroborate ([bpy]BF₄) and [H₂TSPP]²⁺. The studies also suggest that the intermolecular π–π force is of relative importance for the J-aggregates of [H₂TSPP]²⁺ and the intermolecular electrostatic force for the H-aggregates.     

Experimental and theoretical studies on the reactions of 1-amino-5-benzoyl-4-phenyl-1<Emphasis Type="Italic">H</Emphasis>-pyrimidine-2-one/-thione compounds with ethyl acetoacetate

The reaction of 1-amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidin-2(1H)-one/-thione (1a,b) with ethyl acetoacetate (EA) afforded moderate to good yields (59–63%) of ethyl 2-methyl-4-(4-methylbenzoyl)-5-(4-methylphenyl)-7-oxo/-thioxo-3,3a-dihydropyrazolo[1,5-c]pyrimidine-3-carboxylate (2a,b). The newly synthesized compounds were characterized by elemental analyses, IR, ¹H and ¹³C NMR spectral data. All were compared with their previous analogues. The reaction mechanism of 1 with EA was studied by means of the B3LYP/6-31G(d,p) method. In addition, for reactants Fukui functions were performed using the data calculated with the Becke3–Lee–Yang–Parr (B3LYP) hybrid function.