Design and Syntheses of Novel Calix[4]crown: Calix[4]‐Dixanthates‐Crowns

Abstract

A series of novel calix[4]‐dixanthates‐crowns were designed and synthesized by the “1 + 1 condensation” of reacting calix[4]‐1,3‐dixanthate salts derivative (4) with polyethylene glycol ditosylates in 40–60% yields. It was found that the new calixcrowns showed outstanding complexation abilities towards soft cations. Calix[4]‐dixanthate‐crown‐4 (5b) exhibited high complexation selectivity towards Ni²⁺.     

Alkylation of pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one derivatives

Alkylation of 11-benzyl-3,11-dihydro-4H-pyrimido[5′,4′:5,6]pyrido[3,2-b]indol-4-one with methyl iodide and methyl bromoacetate in DMF gave 3-alkylpyrimidopyridoindolones as the corresponding salts. The reaction in acetone in the presence of K₂CO₃ yielded 3,6-disubstitution products. Alkylation with DMF dimethyl acetal gave a mixture of the 3- and 6-alkylpyrimidopyridoindol-4-one bases. The structure of 4-oxo-4,6-dihydro-3H-pyrimido-[5′,4′:5,6]pyrido[3,2-b]indol-11-ium chloride (3b) was proved by X-ray diffraction analysis.     

Synthesis of new pyridazino[4′,3′:4,5]-thieno[3,2-d]-1,2,3-triazine and pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine derivatives

Summary 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (2), 3-substituted 8,9-diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-ones (3a–c), 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (4), 8-chloro-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (5), 8-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazines (6a–h) and 7-substituted 3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-ones(7a–c) were synthesized from 5-amino-3,4-diphenylthieno[2,3-c]pyridazine-6-carboxamide (1).

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Synthese neuer Pyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-und Pyrimido[4,5:4,5]thieno[2,3-c]pyridazin-Derivate

Zusammenfassung Folgende Verbindungen wurden ausgehend von 5-Amino-3,4-diphenylthieno[2,3-c]pyridazin-6-carboxamid (1) synthetisiert: 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-on (2), 3-substituierte 8,9-Diphenylpyridazino[4,3:4,5]thieno[3,2-d]-1,2,3-triazin-4(3H)-one (3a–c), 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8[7H]-on (4), 8-Chlor-3,4-diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin (5), 8-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazine (6a–h) und 7-substituierte 3,4-Diphenylpyrimido[4,5:4,5]thieno[2,3-c]pyridazin-8(7H)-one (7a–c).

     

Synthesis of novel [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d] pyrimidines: Potent EGFR targeting anti-breast cancer agents

In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d]pyrimidine derivatives using in a single [3 + 2] reaction cycloaddition reaction of 3-(3-iodoprop-2-yn-1-yl)thieno[2,3-d]pyrimidin-4(3H)-one ( 4 ) followed by C-C bond coupling with various aryl azides in a PEG-400 medium. All of the newly synthesized compounds were evaluated in vitro for EGFR kinase inhibitory action as well as anti-breast cancer activity against MDA-MB-231 and MCF-7 breast cancer cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 5g and 5i , demonstrated excellent anticancer activity against both cancer cell lines, with IC₅₀ values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.467 ± 0.063 and 0.412 ± 0.081 μM). The in silico studies of five potent compounds 5f , 5g , 5h , 5i , and 5k were also carried out to identify the interactions against the EGFR receptor and found that the energy calculations were covenant with the obtained IC₅₀ values.     

K5[InSe4] and K12[InS4]2(S): New Alkali Chalcogenido Indates with [InQ4]5– ortho Anions

The new chalcogenido ortho indates(III) K₅[InSe₄] and K₁₂[InS₄]₂(S) were synthesized from melts of the elements (Se) [or with S/In₂S₃ as chalcogen source] at maximum temperatures of 700/800 °C. The two potassium salts, which were characterized by means of X-ray single crystal structure analysis, contain isolated tetrahedral ortho anions [InQ₄]^5–. K₅[InSe₄] crystallizes in a new structure type [monoclinic, space group C2/c, a = 2014.2(2), b = 1553.1(2), c = 1661.1(2) pm, β = 94.716(2)°, Z = 16, R₁ = 0.0317]. The complex structure contains two crystallographically different [InSe₄]^5– tetrahedra [d(In ··· Se) = 254.3–263.6 pm], which are arranged into 4⁴ [In(1), A ] and 3².4.3.4 [In(2), B ] nets. These nets are |: ABA ' B ':| stacked along the a axis. The 11 crystallographically independent K⁺ ions are coordinated by four (1×), five (3×) and six (7×) selenido anions [d(K–Se) = 309–415 pm]. The crystal structure and the calculated electronic structure of the pure ortho indate K₅[InSe₄] are compared with the known “double salts” K₉[InSe₄]₂(Se) and K₉[InSe₄](Se₂)(Se), which exhibit selenide (and diselenide) anions in addition to the ortho metallate. Similarly, the new sulfido indate K₁₁[InS₄]₂(S) contains sulfide anions besides the indate tetrahedra. In the chiral structure (K₆[InTe₄](Cl)-type, hexagonal, space group P6₃mc, a = 1026.22(10), c = 752.34(7) pm, Z = 2, R1 = 0.0332) layers of similarly oriented [InS₄] tetrahedra [d(In ··· Se) = 246.6/248.1 pm] are hexagonally |: AB :| stacked along one threefold axis. The additional sulfide anions are centered in K⁺ octahedra. In contrast to the isotypic chloride, only every second polyhedron within the columns of face-sharing K₆ octahedra is statistically occupied by a sulfide ion. Both of the two different K positions exhibit a sixfold coordination by sulfide anions, with K–S distances between 307.1 and 382.1 pm. In the two title compounds, each of the [InQ₄] tetrahedra is overall enclosed by 18 potassium cations. The crystal chemistry of the new indates is discussed and compared with that of the (yet comparatively low number) of alkali chalcogenido metallates(III) of Fe, Al and Ga containing isolated metallate tetrahedra.     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

π-Extension in expanded porphyrins: cyclo[4]naphthobipyrrole

The π-extended cyclo[4]naphthobipyrrole 1a has been prepared via an Fe(III)-mediated oxidative cyclization of an alkyl-substituted naphthobipyrrole. The structure of this new expanded porphyrin, isolated as the deprotonated sulfate salt, was characterized by spectroscopic means, as well through a single crystal X-ray diffraction analysis. Salt 1a displays a total of four well-resolved redox waves as determined by cyclic voltammetry. It also displays bathochromically shifted near-IR absorption maxima compared to the diprotonated forms of nonannulated cyclo[8]pyrroles.     

Synthesis of novel spiro-fused pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines

New pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidines, with an associated spiro-3,3′-oxindole attachment, were prepared by three-component combinations of 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione with a pair of reactants chosen from a pyrazol-5-one, a pyrazole-5-amine, a barbituric acid, or a 6-aminouracil.     

The unusual stability of [NpO2Cl4]2−: Synthesis and characterisation of [NpO2(DPPMO2)2Cl]2[NpO2Cl4] and [Ph3PNH2]2[NpO2Cl4]

The [NpO₂(DPPMO₂)₂Cl][NpO₂Cl₄] complex (where DPPMO₂ = bis(diphenylphosphino)methanedioxide) contains the linear neptunyl group, {NpO₂}²⁺, with two bidentate P=O donor ligands. Coordinating anion Cl^? fills the fifth equatorial coordination site yielding a complex of general formula [NpO₂(DPPMO₂)₂X]₂[Y] (1) (where X = Cl^? and Y = [NpO₂Cl₄]^2?. Reaction between our newly prepared neptunium starting material [NpO₂Cl₂(thf)]_n and phosphinimine ligand produced crystals of [Ph₃PNH₂]₂[NpO₂Cl₄] (2). Compounds 1 and 2 have been structurally characterised.     

Synthesis and reactions of new 4-chloro-2-methylpyrimidino[4′,5′:4,5]thiazolo[3,2-a]-benzimidazoles

Summary 4-Chloro-2-methylpyrimidino[4,5:4,5]thiazolo[3,2-a]benzimidazole (3) was prepared by chlorination of2 which could also be converted directly to 2-methylpyrimidino[4,5:4,5]-thiazolo[3,2-a]benzimidazol-4-thiol (4). Nucleophilic substitution of3 with alcohols, phenols, primary amines, secondary amines, sodium azide, and mercaptoacetic acid gave the corresponding derivatives. The thiol derivative4 was reacted with alkyl/aralkyl halides, phenacyl bromide derivatives, bromoacetone, chloroanilides, bromomalonic ester, and ethyl bromoacetate to afford compounds of potential pharmacological interest.

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Synthese und Reaktionen neuer 4-Chlor-2-methylpyrimidino[4,5:4,5]thiazolo[3,2-a]benzimidazole

Zusammenfassung 4-Chlor-2-methylpyrimidino[4,5:4,5]thiazolo[3,2-a]benzimidazol (3) wurde durch Chlorierung von2, welches auch direkt zu 2-Methylpyrimidino[4,5:5,4]thiazolo[3,2-a]-benzimidazol-4-thiol (4) umgesetzt werden kann, hergestellt. Nucleophile Substitution von3 mit Alkoholen, Phenolen, primären Aminen, sekundären Aminen, Natriumazid und Mercaptoessigsäure ergab die entsprechenden Derivate. Das Thiolderivat4 wurde mit Alkyl/Alkarylhalogeniden, Phenacylbromidderivaten, Bromaceton, Chloraniliden, Brommalonsäureester und Bromessigsäureethylester zu potentiell pharmakologisch interessanten Verbindungen umgesetzt.

     

Efficient Synthesis and Fungicidal Activities of 3,5,6,8-Tetrahydro-4H-thiopyrano[4′,3′ :4,5]thieno[2,3-d]pyrimidin-4-ones

The carbodiimides 4, obtained from reactions of iminophosphorane 3 with aromatic isocyanates, reacted with amines, phenols, or ROH to give 2-substituted 3,5,6,8-tetrahydro-4H-thiopyrano[4′,3′ :4,5]thieno [2,3-d]pyrimidin-4-ones 6 in the presence of a catalytic amount of sodium alkoxide or solid potassium carbonate in satisfactory yields. Compounds 6 exhibited fungicidal activity. For example, compounds 6e, 6m, and 6s showed 70% inhibition activities against Dothiorella gregaria in 100 mg/L.     

Novel Synthesis of Pyrano[2,3-d]Thiazole,Thiazolo[3,2-a]Pyridine,and Pyrazolo [3′,4′:4,5] Thiazolo[3,2-a]Pyridine Derivatives

Cyclocondensation of 2-cyanomethyl-4-thiazolidinone (1) with tetracyanoethylene (2) furnished pyrano[2,3-d]thiazole derivative (4) . Benzo[e]pyrano[2,3-d]thiazole derivative (6) was obtained by cyclization of compound (1) with salicylaldehyde. In a similar manner, condensation of compound (1) with 2-hydroxy-1-naphthaldehyde in refluxing ethanol yielded naphtho[e]pyrano[2,3-d]thiazole derivative (7) . Interaction of compound (9) with benzylidenemalononitriles (10) (1 : 1 molar ratio) at reflux temperature in ethanol in the presence of piperidine afforded thiazolo[3,2-a]pyridines (12a-c) . Treatment of compound (12a) with hydrazines furnished pyrazolo[3′,4′:4,5] thiazolo[3,2-a]pyridines (14a,b) . The reaction of compound (1) with benzyli-denecyanoacetate (16) yielded 5-hydroxythiazolo[3,2-a]pyridine derivative (21) . Cyclization of bis(thiazolinone) (23) with benzylidenemalononitriles (10) produced bis(thiazolopyridine) derivatives (25a,b) .     

Efficient Synthesis of 3,5,6,8-Tetrahydro-4H-thiopyrano[4′,3′:4,5]· thieno[2,3-d]pyrimidin-4-ones via an Iminophosphorane

3,5,6,8-Tetrahydro-4H-thiopyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-ones(7) were synthesized via the base catalytic reactions of amines or phenols with carbodiimides(5), which were obtained from the aza-Wittig reactions of iminophosphoranes(4) with aromatic isocyanates.     

[4+3]环加成反应研究进展

本文对[4+ 3 ]环加成反应体系以及最近在合成中的应用进行了综述, 并对进一步研究的方向进行了讨论。     

Synthesis of New Pyrido[4″,3″:4″,5″]thieno[2″,3″:4,5]pyrimido[2,1-b][1,3,4]thiadiazine Derivatives

Ethyl 2-methyl-11-oxo-9, 10-dihydro-1 H , 11 H -pyrido[4",3":4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 7 has been synthesised by the reaction of ethyl 3-amino-4-oxo-2-thioxo-1,3,4,5,6,8-hexahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7(2 H )-carboxylate 2 with allylbromide followed by treatment with bromine and subsequent dehydrobromination of the brominated product 5 with ethanolic sodium hydroxide. Its isomeric ethyl 2-methyl-11-oxo-9,10-dihydro-3 H ,11 H -pyrido[4",3Prime;:4',5']thieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazine-8(7 H )-carboxylate 8 has been obtained by condensation of 2 with chloroacetone followed by cyclization of the intermediate 9 with p -toulenesulfonic acid. The thiadiazino derivatives 11 , 13 , 15 were prepared through the reaction of 2 with the appropriate f -halocarbonyl compounds followed by cyclization reactions of the intermediates 10 , 12 , 14 .     

Pyridazines,LIV: On the synthesis of pyridazine-fused S-heterocycles: Thieno[2,3-c]pyridazine,pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine,and pyridazino[3,4-b][1,4]benzothiazine

Summary Starting from 3-chloro-4-pyridazinecarbonitrile (1), the thienopyridazine derivatives2 and3 were prepared. Condensation of3 with triethyl orthoformate afforded the novel tricyclic system4. Reaction of1 with 2-aminothiophenol, followed by treatment with NaH/DMSO was found to give the diaza-phenothiazine6 instead of the expected condensed thiazepine.Dedicated with best wishes to Prof. Dr. G. Zigeuner on the occasion of his 70^th anniversary     

Synthesis and structures of mercury and cadmium complexes: [Ph4Sb] 2 + [Hg2I6]2−·Ph2Hg, [Ph4Sb] 2 + [E2I6]2− (E = Hg, Cd), and [Ph4Sb] 2 + [Hg4I10]2−

The reaction of pentaphenylantimony with mercury iodide affords the ionic complex [Ph₄Sb] ₂ ⁺ [Hg₂I₆]^2?·Ph₂Hg (I). The [Ph₄Sb] ₂ ⁺ [Hg₂I₆]^2? (II) and [Ph₄Sb] ₂ ⁺ [Cd₂I₆]^2? (III) complexes are synthesized from tetraphenylantimony iodide and mercury and cadmium iodides. The [Ph₄Sb] ₂ ⁺ [Hg₄I₁₀]^2? complex (IV) is prepared from tetraphenylantimony 2,4-dimethylbenzenesulfonate and mercury iodide. According to the X-ray diffraction data, the Sb atom in the [Ph₄Sb]⁺ cations of complex I has virtually ideal tetrahedral coordination (the CSbC angles are 108.09°–109.64°). In the central square fragment Hg₂I₂ of the [Hg₂I₆]^2? anion, the Hg-I_br bond lengths are 2.825 and 3.075 Å, and the terminal iodine atoms are more strongly bonded to the mercury atoms (Hg-I_term 2.691 and 2.700 Å). The [Cd₂I₆]^2? anion in complex III has a similar structure (the Cd-I_bridg and Cd-I_term distances are 2.865, 2.872 and 2.723, 2.748 Å, respectively). The anions in complex IV are joined by I…Hg (3.651 Å) and I…I (4.058 Å) interactions into an infinite dimeric network.     

Synthesis of New Derivatives Benzo[4′,5′]imidazo[2′,1′:6,1]pyrido[2,3-d]pyrimidine

Russian Journal of Organic Chemistry - The reactions of 4-methyl- and (RS)-4,6-dimethyl-2-phenyl-5,6-dihydrobenzo[4′,5′]imidazo-[2′,1′:6,1]pyrido[2,3-d]pyrimidines and...     

Synthesis of 2,4-disubstituted pyrimido[4,5-b]-indoles,pyrano[4′,3′:4,5]pyrrolo[2,3-d]pyrimidines and some conversions of pyrimido[4,5-d]indoles

Methods have been developed for the production of 2,4-disubstituted 5,6,7,8-tetrahydro-9H-pyrimido[4,5-b]indoles and pyrano[43:4,5]pyrrolo[2,3-d]pyrimidines. Heterocyclization reactions were carried out on 4-hydrazinopyrimido[4,5-b]indoles.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Erevan, 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10. pp. 1413–1416, October, 1996. Original article submitted June 21, 1996.     

2-[Pyridin-2(4)-yl]-N-[ω-vinyloxyalkyl]ethanamines

Russian Journal of Organic Chemistry -