Preparation of 4,6-diaminopyrazolo[3,4-d] pyrimidines with variations in substitution at the 1- and 3-positions

A number of new derivatives of 4,6-diaminopyrazolo[3,4-d]pyrimidines substituted in the 1- and/or 3-positions have been obtained from reactions of guanidine carbonate with 1- and/or 3-substituted-5-amino-4-cyanopyrazoles. Use of triethanolamine as a reaction medium permitted preparation of certain derivatives which could not be obtained from the previously described fusion procedure. Some derivatives of 4-aminopyrazolo[3,4-d]pyrimidine with substitution at the 1 - and/or 3-positions were also obtained from reactions of formamide with the same 5-amino-4-cyanopyrazoles. The new compounds were screened for in vivo antimalarial activity, but were found inactive.     

Studies in azide chemistry. Part IX [1]. Investigations involving fluorinated azidopyrimidines and 4-azido-3-chloro-2,5,6-trifluoropyridine

4-Azido-2,5,6-trifluoro- and 4,6-diazido-2,5-difluoro- pyrimidine were obtained by treating tetrafluoropyrimidine with sodium azide in acetonitrile; similar azidation of 5-chlorotrifluoropyrimidine gave 4-azido-5-chloro-2,6-difluoro- and 4,6-diazido-5-chloro-2-fluoro-pyrimidine. Each monoazide reacted with triphenylphosphine to yield the corresponding iminophosphorane (Staudinger reaction), and the trifluoro- compound gave cycloadducts when heated with phenylacetylene [→ 4-phenyl-1-(2,5,6-trifluoro-4-pyrimidinyl)-1,2,3- triazole] and acrylonitrile [→ 2-cyano-1-(2,5,6-trifluoro- 4-pyrimidinyl)aziridine]; attack on the trifluoro-azide by the sodium salt of pentafluoroaniline produced 4-azido-2,5- difluoro-6-(pentafluorophenylamino)pyrimidine and bis(4- azido-2,5-difluoro-6-pyrimidinyl)(pentafluorophenyl)amine. Attempts to intercept nitrenes during thermal decomposition of both mono-azides failed. Thermolysis of 4-azido-3-chloro- 2,5,6-trifluoropyridine in the presence of dimethyl sulphoxide, cyclohexane, or pentafluoroaniline gave products [py_FNS(O)Me₂, py_FNHC₆H₁₁, and py_FNNPh_F (PY_F = 3-chlorotrifluoro-4-pyridyl), respectively] compatible with release of the corresponding nitrene.     

Copolyamides of nylon-4,6 and nylon-4,T

Copolyamides of nylon-4,6 and nylon-4,T were prepared by a two-step method: (1) a prepolymerization in an autoclave (40 min at 210°C) and (2) a postcondensation in the solid state (4 h, 260°C). On these materials was studied the melting behavior with DSC, the crystalline structure with WAXS, the water absorption, and the mechanical properties with a torsion pendulum. In these copolyamides the order was found to remain high, but the crystalline structures of -4,6 and -4,T were not isomorphous. The torsion moduli increased with -4,T content both at RT and at 140°C.     

Synthesis and Characterization of Some Ruthenium Mixed-Ligand Complexes

The complexation reaction of trans-[RuCl₂(Dpte)₂] (Dpte – (diphenylthio)ethane) with mixed diimine ligands 2,2"-bipyridine, pyridylquinoline, 4,6-dichloro-2-(2-pyridyl)pyrimidine, 4,6-dichloro-5-methyl-2-(2-pyridyl)pyrimidine, and 4,6-dichloro-5-phenyl-2-(2-pyridyl)pyrimidine produces new Ru(II) mixed-ligand complexes. These complexes exhibit maximum photo- and chemical stability and high absorptivity. The above complexes have been characterized using IR, ¹H and ¹³C NMR, electronic absorption spectroscopy, and elemental analysis.     

A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives: their synthesis and fluorescence properties for anion sensors

A new series of 2,5-bis(4-methylphenyl)-1,3,4-oxadiazole derivatives containing various substituted groups on the ortho-position to oxadiazole ring was synthesized and their fluorescent sensor properties were investigated. The fluorescent sensor molecules showed UV absorption shift as well as fluorescence emission shift upon exposure to fluoride anion in DMF solution, which was considerably dependent on the substituent attached on the phenyl group. The new sensory compound, 1d can be used as a fluoride anion sensor in terms of naked-eye detection and fluorescent sensing with high selectivity.     

The structure of the cations from 2– and 4-pyrimidones

An infrared spectral investigation of a number of pyrimidine and pyrimidone hexachloroantimonates is reported. Typical aromatic absorption bands found in pyrimidinium salts were absent in the pyrimidone cations. 2-And 4-Pyrimidone hexachloroantimonates, as well as their N-methyl- and N,N'-dimethyl derivatives, exhibit intense carbonyl absorption bands between 1720–1729 cm^?1 (solid state) which corroborates N-protonation of pyrimidones.     

Photoreactivating Enzyme for (6–4) Photoproducts in Cultured Goldfish Cells

We previously reported that when cultured goldfish cells are illuminated with fluorescent light, photorepair ability for both cyclobutane pyrimidine dimers and (6–4) photoproducts increased. In the present study, it was found that the duration of the induced photorepair ability for cyclobutane pyrimidine dimers was longer than that for (6–4) photoproducts, suggesting the presence of different photolyases for repair of these two major forms of DNA damage. A gel shift assay was then performed to show the presence of protein(s) binding to (6–4) photoproducts and its dissociation from (6–4) photoproducts under fluorescent light illumination. In addition, at 8 h after fluorescent light illumination of the cell, the binding of pro-tein(s) to (6–4) photoproducts increased. The restriction enzymes that have recognition sites containing TT or TC sequences failed to digest the UV-irradiated DNA pho-toreactivated by using Escherichia coli photolyase for cyclobutane pyrimidine dimers, indicating that restriction enzymes could not function because (6–4) photoproducts remained in recognition sites. But, when UV-irradiated DNA depleted of cyclobutane pyrimidine dimers was incubated with extract of cultured goldfish cells under fluorescent light illumination, it was digested with those restriction enzymes. These results suggested the presence of (6–4) photolyase in cultured goldfish cells as in Dro-sophila, Xenopus and Crotalus.     

Synthesis of Diheteroarylamine Ligands by Palladium‐Catalyzed Mono‐ and Diamination of Dichlorohetero­arenes with Heteroarenamines

The syntheses of bidentate (see 6 and 12 ), bis‐bidentate ( 7, 10 , and 13 ) up to oligo‐bidentate (see 11 and 14 ) diheteroarylamine‐based N,N‐ligands are reported (Tables 2, 4, and 5). In the course of investigations on heteroaromatic (C? N)‐bond formations, a protocol for the Pd‐catalyzed mono‐ and diamination of 2,6‐dichloropyridine ( 1 ) and 4,6‐dichloropyrimidines 5 with heteroaren‐2‐amines 2 and pyrimidine‐4,6‐diamines 8 is developed. The results are applied to the syntheses of the ‘pentamers’ 11a – 11d and the ‘heptamer’ 14 based on 4,6‐disubstituted 2‐alkylpyrimidines 5 and 8 , respectively.     

Dynamic Properties of Molecular Tweezers with a Bis(2‐hydroxyphenyl)pyrimidine Backbone

4,6‐Bis(2‐hydroxyphenyl)‐2‐alkylpyrimidines with two anthryl or 9‐ethylnylanthryl substituents at the positions para to the OH groups prefer a U‐shaped conformation supported by two intramolecular OH ??? N hydrogen bonds in the solid state and in CDCl₃ solution. The compound with a hexyl substituent on the pyrimidine group and two 9‐ethynylanthryl arms at the hydroxyphenyl groups forms a 1:1 complex with 2,4,7‐trinitrofluorenone. Its association constant K_a was estimated to be 2100 M ^?1 at 298 K, which is larger than those of other molecular tweezers (K_a<1000 M ^?1). DFT calculations suggested that the complex adopts a stable conformation supported by intramolecular hydrogen bonds among the OH groups and the pyrimidine ring as well as by intermolecular π–π interaction between the anthryl groups and 2,4,7‐trinitrofluorenone. Addition of nBu₄NF to a solution of the molecular tweezers or their complexes causes the cleavage of one or two OH ??? N hydrogen bonds, formation of new O ??? HF hydrogen bonds, and changes in the molecular conformation. The resulting structure of the molecular tweezers contains nonparallel anthryl groups, which do not bind the guest molecule. Photochemical measurements on 4,6‐bis(2‐hydroxyphenyl)‐2‐methylpyrimidine with two anthryl substituents showed negligible luminescence (quantum yield ?<0.01), owing to photoinduced electron transfer of the molecule with a U‐shaped structure. However, the O‐hexylated compound exhibits emission from the anthryl groups with ?=0.39.     

Practical synthesis of potential endothelin receptor antagonists of 1,4-benzodiazepine-2,5-dione derivatives bearing substituents at the C3-, N1- and N4-positions

The expedient synthesis of various 1,4-benzodiazepine-2,5-dione compounds, particularly those having substituents at the C3-, N1- and N4-positions is achieved. The important features in these synthetic strategies include: (i) using the coupling reaction of isatoic anhydride with alpha-amino ester for direct construction of the core structure of 1,4-benzodiazepine-2,5-dione; (ii) using potassium carbonate as the base of choice for selective alkylation at the N1-site, while using lithiated 2-ethylacetanilide as the required base to furnish the N4-alkylation; and (iii) using 2-nitrobenzoyl chloride as a synthetic equivalent of anthranilic acid to facilitate the polyethylene resin-bound liquid-phase combinatorial synthesis. The prepared 1,4-benzodiazepine-2,5-dione compounds are evaluated for endothelin receptor antagonism by a functional assay that measures the inhibitory activity against the change of intramolecular calcium ion concentration induced by endothelin-1. The preliminary results indicate that 1,4-benzodiazepine-2,5-diones bearing two flanked aryl substituents at the N1- and N4-sites show better inhibitory activity than the corresponding unalkylated and N-monoalkylated compounds. A promising candidate, 1-benzyl-7-chloro-3-isopropyl-4-(3-methoxybenzyl)-1,4-benzodiazepine-2,5-dione (17b), exhibits an IC50 value in low nM range.     

Synchronized motion and electron transfer of a redox-active rotor

We have constructed a series of copper complexes with asymmetric 4,6-substituted 2-pyrimidyl coordination units, which form two coordination isomers via rotation of the pyrimidine ring. Redox-active ferrocenyl moieties were introduced at the 4-positions of the pyrimidine as rotating units in these complexes. The stability and dynamics of the rotative interconversion could be tuned using the structure of the rotor to accommodate a large ferrocene unit within the inner space of the complex. Among these compounds, a complex with a ferrocenylvinyl substituent showed synchronized intramolecular electron transfer between the copper and the ferrocenyl moiety with rotational motion. That is, the oxidation state of the ferrocenyl unit depended on its position within a cyclic trajectory.     

Strongly coupled excitonic states in H-aggregated single crystalline nanoparticles of 2,5-bis(4-methoxybenzylidene) cyclopentanone

This paper reports that extremely strongly coupled excitonic states were formed in H-aggregated monocrystalline nanosheets and semicrystalline nanowires of coplanar organic molecules of 2,5-bis(4-methoxybenzylidene) cyclopentanone, due to the highly regular face-to-face stacking of molecular excitons. It was demonstrated that the spectral absorption and fluorescence emission behaviors are dependent on the routes of molecular aggregation and the ordered degree of molecular arrangement in aggregated nanoparticles. In particular, the H-type aggregation of molecules through a highly ordered molecular arrangement in the monocrystalline nanosheets led to the formation of a new exciton coupling state with an energy band higher than that in normal semi-/noncrystalline H-aggregation. A strong symmetric absorption at higher energy bands was thus observed in the solution of nanosheets. Furthermore, the strongly coupled excitonic state may hold all the oscillator strength, leading to the extinction of the original intramolecular electronic transitions of individual molecules and the appearance of new strong absorption and fluorescence emissions at high-energy bands. These results show a perspective that the ability to control the molecular structure and its arrangement in aggregates holds promise for creating novel optical properties in molecular materials.     

Amination of 4,6- and 2,4-dichloropyrimidines with polyamines

Amination of a double excess of 4,6-dichloropyrimidine with various diamines in the presence of cesium carbonate in boiling dioxane quantitatively afforded the corresponding N,N′-bis(6-chloropyrimidin-4-yl) derivatives, while its reactions with tri- and tetraamines gave N,N′,N″-tris- and N,N′,N″,N‴-tetrakis(6-chloropyrimidin-4-yl) derivatives. Equimolar amounts of 2,4-dichloro- or 4,6-dichloropyrimidine and diamines reacted in the presence of Pd(0) complexes to form macrocyclic compounds containing pyrimidine fragments. Catalytic reactions of 4 equiv of diamines with 4,6-dichloropyrimidine can lead to the formation of 4,6-bis-(diamino)pyrimidines. Relations between the yield and the nature of diamine and catalytic system were found.     

Hydrogen bonding in nitroaniline analogues: hydrogen‐bonded sheets in 2‐amino‐4,6‐dimethoxy‐5‐nitropyrimidine and π‐stacked hydrogen‐bonded sheets in 4‐amino‐2,6‐dimethoxy‐5‐nitropyrimidine

In 2‐amino‐4,6‐di­methoxy‐5‐nitro­pyrimidine, C₆H₈N₄O₄, the mol­ecules are linked by one N—H⋯N and one N—H⋯O hydrogen bond to form sheets built from alternating R(8) and R(32) rings. In isomeric 4‐amino‐2,6‐di­methoxy‐5‐nitro­pyrimidine, C₆H₈N₄O₄, which crystallizes with Z′ = 2 in P, the two independent mol­ecules are linked into a dimer by two independent N—H⋯N hydrogen bonds. These dimers are linked into sheets by a combination of two‐centre C—H⋯O and three‐centre C—H⋯(O)₂ hydrogen bonds, and the sheets are further linked by two independent aromatic π–π‐stacking interactions to form a three‐dimensional structure.     

Synthesis of polypyridazinophthalazinediones from dibenzoylphthalic acids and aromatic dihydrazines

A novel class of polypyridazinophthalazinediones has been synthesized by the solution cyclopolycondensation in m-cresol of dibenzoylphthalic acids with aromatic dihydrazines such as bis(4-hydrazinophenyl)methane and bis(4-hydrazinophenyl) sulfone. The polyheterocycles derived from 4,6-dibenzoylisophthalic acid, which had inherent viscosities of up to 0.5, were soluble in m-cresol and hot dichloroacetic acid, whereas the polymers from 2,5-dibenzoylterephthalic acid were practically insoluble in organic solvents. Thermogravimetric analyses showed that all the polymers underwent weight losses of 10% at 490–520°C in both air and nitrogen.     

Synthesis and Crystal Structure of 4-（4,6-Dimethoxylpyrimidin-2-yl）- 3-thiourea Carboxylic Acid Ethyl Ester

4-（4,6-Dimethoxyl-pyrimidin-2-yl）-3-thiourea carboxylic acid ethyl ester was synthesized by the reaction of 2-amino-4,6-dimethoxyl pyrimidine, potassium thiocyanate and methyl chloroformate in ethyl acetate. Single crystals suitable for X-ray measurement were obtained by recrystallization with the solvent of dimethyl formamide at room temperature. The crystal structure was determined by X-ray diffraction analysis. Crystallographic data： C10H14N4O4S, M, = 286.31, monoclinic, space group C2/c with a = 2.5309（3）, b = 0.67682（6）, c = 1.74237（19） nm, β = 114.744（3）°, V= 2.7106（5） nm3, Dc = 1.403 g/cm3, p = 0.225 mm-1, F（000） = 1200, Z= 8, R= 0.0514 and wR= 0.1529.     

Synthesis and Crystal Structure of N3-（Dimethyl- pyrimidine）-N4-（tri-O-acetyl-xylosyl） Thiourea

The crystal structure of the title compound （C18H24N4O7S, Mr = 440.47） was prepared by the condensation of 2,3,4-tri-O-acetyl-β-D-xylopyranosyl isothiocyanate with 4,6-dimethylpyrimidin-2-amine and structurally determined by single-crystal X-ray diffraction. The crystal belongs to the monochnic system, space group P2 1 with a = 7.5500（17）, b = 10.498（2）, c = 14.208（3） A, β = 99.929（4）°, V = 1109.2（4） A^3, Z = 2, Dc = 1.319 g/cm^3,μ = 0.191, F（000） = 464, Flack = 0.00（15）, R = 0.0684 and wR = 0.1103. In the crystal structure, the xylose ring adopts a ^4C1 chair conformation. Due to the hydrogen bonding interaction between N（4）-H（4A） and N（1）, the pyrimidine ring is well positioned.     

Pyrimidine-core extended pi-systems: general synthesis and interesting fluorescent properties

We have developed a simple but powerful synthetic strategy that permits the assembly of pi-systems onto a pyrimidine core in a programmable and diversity-oriented format. The nucleophilic addition of ArLi to 2-methylthiopyrimidine, followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation, resulted in the production of 4-aryl-2-methylthiopyrimidines. The iterative reaction sequence then gave 4,6-diaryl-2-methylthiopyrimidines. The resulting adduct was further allowed to react with ArMgBr under the catalytic influence of NiCl2(dppe) to afford 2,4,6-triarylpyrimidines. By following this synthetic scheme, interesting pyrimidine-core pi-systems were rapidly constructed in a programmable fashion. The successful discovery of a number of interesting fluorescent materials and properties (e.g., solvatofluorochromism) speaks well for the potential of our platform strategy in the development of functional organic materials.     

Synthesis of highly refractive polyimides derived from 3,6‐bis(4‐aminophenylenesulfanyl)pyridazine and 4,6‐bis(4‐aminophenylenesulfanyl)pyrimidine

A series of aromatic polyimides (PIs) containing pyridazine or pyrimidine in their main chains has been developed. All of the PIs were prepared from newly synthesized diamines, 3,6‐bis(4‐aminophenylenesulfanyl)pyridazine (APP), 4,6‐bis(4‐aminophenylenesulfanyl)pyrimidine (APPM) and aromatic dianhydrides, 4,4′‐[p‐thiobis(phenylenesulfanyl)]diphthalic anhydride (3SDEA) and 4,4′‐oxydiphthalic anhydride (ODPA) via the conventional two‐step polycondensation. The PIs showed good thermal stability with 10% weight loss at temperatures above 450 °C and glass transition temperatures above 190 °C. Films with a 10‐μm thickness exhibited good optical transparency above 80% at 500 nm, high refractive indices ranging from 1.7218 to 1.7499, and low birefringence between 0.0066 and 0.0102. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4886–4984, 2009     

Influence of solvent and substituent on excited state characteristics of laser grade coumarin dyes

Absorption and fluorescence emission of 4 and 7 substituted coumarins viz. C 440, C 490, C 485 and C 311 have been studied in various polar and non-polar organic solvents. These coumarin dyes are substituted with alkyl, amine and fluorine groups at 4- and 7-positions. They give different absorption and emission spectra in different solvents. The study leads to a possible assignment of energy level scheme for such coumarins including the effect on ground state and excited state dipole moments due to substitutions. Excited state dipole moments of these dyes are calculated by solvetochromic data experimentally and theoretically these are calculated by PM 3 method. The dipole moments in excited state, for all molecules investigated here, are higher than the corresponding values in the ground state. The increase in dipole moment has been explained in terms of the nature of excited state and resonance structure.