A study of the physico-chemical properties of 1,3,5-trihydroxy-1,3,5-triazin-2,4,6[1H,3H,5H]-trione

Acetyl (Ia) and pivaloyl (Ib) triesters of the 1N,3N,5N-trihydroxy-1,3,5-triazin-2,4,6[1H,3H,5H]-trione (I) were synthesised. The spectrophotometric and potentiometric investigation of I revealed a weak acidic properties of triprotonic acid (pK_a1=5.23, pK_a2=6.32, and pK_a3=7.93). The MS and TGA analyses of I indicated on hydroxyisocyanate as possible degradation product. The chelating ability of I with Fe(III)-ion was preliminary explored. IR measurements of aqueous solutions of I in the presence of Fe(III) ion showed the possible chelating ability of all hydroxamic moieties. The chemical structures and properties of investigated compounds were derived from the results of IR, ¹H and ¹³C NMR, UV and MS spectrometric data, as well as thermogravimetric and potentiometric analysis.     

An unexpected multicomponent reaction leading to 2-arylpyrrolo[2,3,4-kl]acridin-1(2H)-ones

An unexpected condensation profile was observed for the three-component reaction of 5,5-dimethyl-1,3-cyclohexadione (dimedone), various anilines, and isatin leading to the synthesis of novel 2-arylpyrrolo[2,3,4-kl]acridin-1(2H)-ones in the ionic liquid [HMIm]HSO₄. Regeneration of the enamine group after the initial condensation reaction associated with participation of the restored amine group in translactonization with the pyrrolidone ring are suggested as the main differentiating events being favored over addition of the second dimedone molecule, with respect to similar reported reactions.     

Reductive opening of 1H,3H-benzo[de]isochromene: synthesis of 1,8-difunctionalised naphthalenes

The lithiation of 1H,3H-benzo[de]isochromene (6) with lithium and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5% molar) in THF at −50 °C gives dianionic intermediate 7, which by reaction with different electrophiles {H₂O, D₂O, ^tBuCHO, PhCHO, Me₂CO, (CH₃CH₂)₂CO, [CH₃(CH₂)₄]₂CO, (CH₂)₅CO, (CH₂)₇CO, (−)-menthone} at the same temperature followed by hydrolysis leads to functionalised alcohols 8. If after addition of a carbonyl compound as the first electrophile [^tBuCHO, (CH₂)₅CO, (−)-menthone], the resulting dialcoholate 9 is allowed to react at 0 °C, a second lithiation takes place to give intermediate 10 which by reaction with a second electrophile [H₂O, ^tBuCHO, (CH₂)₅CO, CO₂], yields, after hydrolysis, 1,8-difunctionalised naphthalenes 11. Cyclization under acidic conditions of diols 8e-i gives oxygen-containing eight-membered heterocycles, which are homologous to the starting material 6.     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

A novel sulfonic acid functionalized ionic liquid catalyzed multicomponent synthesis of 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione derivatives in water

Three-component reactions of 4-hydroxycoumarin, aldehydes, and cyclic 1,3-dicarbonyl compounds were prompted by novel sulfonic acid functionalized ionic liquids 1,3-dimethyl-2-oxo-1,3-bis(4-sulfobutyl)imidazolidine-1,3-diium hydrogen sulfate ([DMDBSI]·2HSO₄) in water at reflux temperature to provide a novel series of 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione derivatives for the first time in high yields.     

Isoquinolin-1(2H)-ones and 1,6-naphthyridin-5(6H)-ones by an N-acylation-SNAr sequence

A new synthesis of 2,3-dialkyl-4-carbomethoxyisoquinolin-1(2H)-ones and 6,7-dialkyl-8-carbomethoxy-1,6-naphthyridin-5(6H)-ones is reported. The process involves treatment of a β-enaminoester with 2-fluoro-5-nitrobenzoyl chloride, 2-fluorobenzoyl chloride or 2-chloronicotinoyl chloride followed by heating in the presence of base. The conversion, which proceeds by an N-acylation-S_NAr reaction sequence, affords 50–86% yields when R¹ is n-alkyl but ≤30% yields when R¹ is α-branched.     

Di(1H,1H,2H,2H-perfluorooctyl)-dibenzo-18-crown-6: A “light fluorous” recyclable phase transfer catalyst

A series of dibenzo-18-crown-6 lariat ethers containing two C₇H₁₅ (11), (CH₂)₂C₆F₁₃ (14), (CH₂)₂C₈F₁₇ (15), NHC₇H₁₅ (18) and NHCH₂C₆F₁₃ (19) sidearms were prepared and the single crystal X-ray structure of cis-4,4′-di(1H,1H,2H,2H-perfluorodecyl)-dibenzo-18-crown-6 (15a) is reported. The “light fluorous” dibenzo-18-crown-6 ether (14) has emerged as a stable and robust PTC catalyst, which can be recycled efficiently by fluorous solid-phase extraction, and gives better PTC catalytic activity compared to the parent, non-fluorinated PTC catalyst, dibenzo-18-crown-6, and the alkylated derivative (11) in aliphatic and aromatic nucleophilic substitutions.     

Stereoselective reductions of N-Boc-hexahydro-1H-indolin-5(6H)-ones

We report the divergent effects of a 3a-methyl and 3a-phenyl substituent on the chemoselectivity and stereoselectivity of reduction of the enamide moiety of N-Boc-hexahydro-1H-indolin-5(6H)-ones. Under ionic reduction conditions (triethylsilane/trifluoroacetic acid) the enamide group of 3a-methyl-N-Boc-hexahydro-1H-indolin-5(6H)-one was reduced to afford exclusively a cis ring-fused product. For the 3a-phenyl substituted analogue more forcing conditions (sodium cyanoborohydride at pH 2-2.5) were required and resulted in the selective reduction of the enamide group to give a trans ring-fused product as well as reduction of the ketone group.     

Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of primaquine: scope and limitations

The synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (±)-primaquine with N^α-protected amino acids, (ii) removal of the N^α-protecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic acid in the third step afforded 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. All products were isolated in good to excellent yields. Whereas imidazolidin-4-ones were formed as mixtures of all possible diastereomers in equal amounts, 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones were produced in a stereoselective fashion. The compounds hydrolyse very slowly (t_1/2 5-30 d) in pH 7.4 buffer to release primaquine. These primaquine derivatives are being submitted to biological assays, and preliminary results of their antimalarial activity are quite encouraging.     

IM-16: A new microporous germanosilicate with a novel framework topology containing d4r and mtw composite building units

The synthesis and the structure of IM-16 a new germanosilicate with a novel zeolitic topology prepared hydrothermally with the ionic liquid 3-ethyl-1-methyl-3H-imidazol-1-ium as the organic structure-directing agent are reported. The structure of calcined and partially rehydrated IM-16 of chemical formula |(H₂O)_0.16|[Si_3.47Ge_2.53O₁₂] was solved from powder XRD data in space group Cmcm with a=15.0861(2) Å, b=17.7719(3) Å, c=19.9764(3) Å, V=5355.84(12) Å³ (Z=16). This new zeolite framework type contains 10-MRs channels and may be described from the d4r and mtw composite building units.     

6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione: new heterocyclizations based on SN-methodology. Unexpected formation of the first iso-π-electronic analogue of the still unknown dibenzo[a,o]pycene

N₍₂₎-Oxide and 3-amino derivatives of 6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione have been shown to react with primary alkylamines in the presence of an oxidant to produce condensed imidazolines or imidazoles. Both conversions based on S_N^H-strategy represent a new approach to imidazoline-(imidazole-)ring annulation. Heterocyclic analogues of the still unknown dibenzo[a,o]pycene were obtained as a by-products of the above transformations upon using of cyclohexylamine.     

Synthesis and reactions of 1-hydroxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2-(3H)-ones

1-Hydroxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-ones, as a new type of azaheterocyclic hydroxamic acids, have been synthesized regioselectively from 1-carbamoylmethyl- or 1-(methoxycarbonyl)methyl-2,3,3-trimethyl-3H-indolium salts by reaction with hydroxylamine in the presence of a strong base. The alkylation and reduction with sodium borohydride of these novel heterocycles have been investigated. When treated with protic acids 1-hydroxy- or 1-alkoxy-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-ones underwent ring opening of the imidazolidine to afford 1-[2-(hydroxyamino)-2-oxoethyl]-2,3,3-trimethyl-3H-indolium salts. The structural assignments are based on extensive ¹H, ¹³C and ¹⁵N NMR spectroscopic studies and single crystal X-ray analyses.     

Substituent effects in the ring-chain tautomerism of 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines

Condensation of Betti base analogue amino naphthols with substituted benzaldehydes led to 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines (3-9) which proved to be three-component (r¹-o-r²) tautomeric mixtures in CDCl₃ at 300 K. The electronic effects of the 3-aryl groups on the ratios of the ring-chain tautomeric forms at equilibrium could be described by the equation log K_X=ρσ⁺+log K_X=H. The value of the intercept was found to be strongly influenced by the steric arrangement of the 1,3-diaryl substituents.     

Ring transformation of cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium ion to the corresponding pyrrole derivatives via troponeimine intermediates: photo-induced autorecycling oxidizing reactions of some amines

Ring transformation of 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]furan- 8(7H),10(9H)-dionylium tetrafluoroborate 4⁺·BF₄⁻ to 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrrole-8(7H),10(9H)-dionylium tetrafluoroborate 6a-d⁺·BF₄⁻ consists of the reaction of 4⁺·BF₄⁻ with amines and subsequent exchange of the counter-ion using aq. HBF₄. Reactions of 4⁺·BF₄⁻ with aniline and 4-substituted anilines afforded the corresponding pyrrole derivatives 6a-c⁺·BF₄⁻ directly in good yields. On the other hand, reaction of 4⁺·BF₄⁻ with benzylamine gave the troponeimine intermediate 9, which was not converted to 6d⁺·BF₄⁻ and reverted to 4⁺·BF₄⁻ by adding HBF₄; however, it was converted to 6d⁺·BF₄⁻ upon treatment with (COCl)₂ or SOCl₂, followed by exchange of the counter-ion. In a search for the characteristics of 9, inspection and comparison of the X-ray crystal analyses, NMR and UV-vis spectra, and CV measurement of 9 and N,N-disubstituted troponeimine derivatives 12 were carried out to suggest the remarkable structure of 12 having ionic C-O bonding between the imine-carbon atom and the oxygen atom of the barbituric acid moiety in the solid state. Thus, characteristics of 9 were ascribed to the sterically hindered and favorable conformation of N-protonated troponeimine intermediates. Furthermore, novel photo-induced oxidation reactions of a series of 4⁺·BF₄⁻, 5⁺·BF₄⁻, and 6a,e⁺·BF₄⁻ towards some amines under aerobic conditions were carried out to give the corresponding imines in 455-8362% yields [based on compounds 4⁺, 5⁺, and 6a,e⁺], suggesting the oxidation reaction occurs in an autorecycling process. Mechanistic aspects of the amine-oxidation reaction are also postulated.     

Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride

By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO₂ proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO₂ by using TBAF as a catalyst.     

Ionic liquid phase organic synthesis (IoLiPOS) methodology applied to the three component preparation of 2-thioxo tetrahydropyrimidin-4-(1H)-ones under microwave dielectric heating

An ionic liquid phase organic synthesis (IoLiPOS) has been developed for the preparation of 2-thioxo tetrahydropyrimidin-4(1H)-ones. Treatment of the starting poly(ethyleneglycol)ionic liquid phases (PEG_n-ILPs) 1 with acryloyl chloride 2 afforded a serie of (PEG_n)-ILPs bound acrylate 3 in quantitative yields. Michael addition of aliphatic primary amines 5 to the PEG₁-ILPs 3(a,d) allowed the preparation of β-aminoesters 6 in high yields. Addition of alkyl isothiocyanates 7 to 6 gave the corresponding thioureido esters 8 in the third step. The final cyclization-cleavage under microwave/solventless strategy provides, under basic conditions, the expected 2-thioxo tetrahydropyrimidin-4(1H)-ones 9 in high purity after flash chromatography. According to the IoLiPOS methodology, the NMR method was used to establish loading of all the PEG-ionic liquid phases intermediates.     

Preparation, spectroscopic properties of 1,4-di (N,N-diisopropylacetamido)-2,3(1H,4H)-quinoxalinedione (L) lanthanide complexes and the supramolecular structure of [Nd2L2(NO3)6(H2O)2]·H2O

The reaction of lanthanide nitrate with 1,4-di (N,N-diisopropylacetamido)-2,3(1H,4H)-quinoxalinedione (L) yields six novel Ln(III) complexes ([Ln₂L₂(NO₃)₆(H₂O)₂]·H₂O) which are characterized by elemental analysis, thermogravimetric analysis (TGA), conductivity measurements, IR, electronic and ¹H NMR spectroscopies. A new quinoxalinedione-based ligand is used as antenna ligand to sensitize the emission of lanthanide cations. The lowest triplet state energy level of the ligand in the nitrate complex matches better to the resonance level of Eu(III) and Sm(III) than Tb(III) and Dy(III) ion. The f-f fluorescence is induced in the Eu³⁺ and Sm³⁺ complexes by exciting into the π-π* absorptions of the ligand in the UV. Furthermore, the crystal structures of a novel binuclear complex [Nd₂L₂(NO₃)₆(H₂O)₂]·H₂O has been determined by single-crystal X-ray diffraction. The binuclear [Nd₂L₂(NO₃)₆(H₂O)₂]·H₂O complex units are linked by the intermolecular hydrogen bonds and π-π interactions to form a two-dimensional (2-D) layer supramolecule.     

The direct arylation of 1,3,5-triazin-2,4(1H,3H)-dione

Direct introduction of non-activated arenes to 1,3,5-triazin-2,4(1H,3H)-dione in the presence of AlCl₃ is described.     

Efficient one-pot syntheses of 2H-indazolo[2,1-b] phthalazine-triones by catalytic H2SO4 in water-ethanol or ionic liquid

Sulfuric acid-catalyzed, three-component, one-pot condensation of phthalhydrazide, aromatic aldehydes and 1,3-dicarbonyl compounds has been reported for the synthesis of a series of 2H-indazolo[2,1-b] phthalazine-triones in water-ethanol or in ionic liquid. The protocol proves to be efficient and environmentally benign in terms of high yields, low reaction times, ease of recovery, and reusability of reaction medium (ionic liquid).     

New iminophosphorane-mediated synthesis of thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes

Mono(iminophosphorane) 4 was selectively prepared from the reaction of 3,4-diaminothieno[2,3-b]thiophene 3 with excess triphenylphosphine, C₂Cl₆, and Et₃N due to intramolecular double hydrogen bond formation. Mono(iminophosphorane) 4 reacted with aromatic isocyanates to give stable carbodiimides 8, which were further treated with aliphatic secondary or primary amines to give 2-amino substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 10 or 12 in the presence of a catalytic amounts of EtO⁻Na⁺. However, in the presence of a catalytic amounts of potassium carbonate, the carbodiimides 8 were transformed into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes 13 via direct cyclization in high yields. The reaction of carbodiimides 8 with phenols in the presence of a catalytic amounts of potassium carbonate gave a mixture of 2-aryloxy substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 14 and 13. X-ray structure analysis of 10m supported the structure and the proposed reactivity of amino group.