Picrylamino-substituted heterocycles. VI. Pyrimidines

The condensation of various aminopyrimidines with picryl chloride and picryl fluoride has been investigated as part of our continuing effort in the field of picrylamino-substituted heterocycles. Most of the aminopyrimidines that can tautomerize reacted with picryl fluoride to form picryl derivatives of their imino forms, but they gave picrylamino derivatives when they condensed with picryl chloride.     

Magnetische Kernresonanz-Untersuchungen über die struktur der Komplexe aus Nitroaromaten mit azid-ionen 9. Mitteilung über nucleophile aromatische Subsitutionsreaktionen [1]

1. NMR. spectra of solutions of tetraethylammonium azide and 2,4,6-trinitro;benzene derivatives (methyl picrate, picryl chloride and picryl azide, respectively) demonstrate that the reactants probably form σ complexes.     

Synthesis of 2,4,6-trinitrophenyl derivatives of heterocyclic compounds

The preparation of 2,4,6-trinitrophenyl (picryl) derivatives of triazine, pyrimidine, thiophene, furan, thiazole, 1,3,4-oxadiazole and 1,3,4-thiadiazole is described. The picryl derivatives are prepared by the Ullmann reaction and by cyclization reactions to form the heterocyclic ring.     

Picrylamino-substituted heterocycles. II. Furazans

This paper describes the synthesis of the various picrylamino- and nitro-substituted furazans and bifurazanyls. Except for 3,4-bis(picrylamino)furazan, which was obtained by nitrating 3,4-dianilinofurazan, the picrylaminofurazans were prepared by condensing the appropriate amino-furazan with picryl fluoride in the presence of triethylamine. The various aminofurazans were oxidized with peroxytrifluoroacetic acid to the corresponding nitro derivatives.     

Picrylamino-substituted heterocycles. IV. Pyrazoles

This paper describes the synthesis of various picryl- and picrylamino-substituted pyrazoles. These compounds were prepared by condensing the appropriate pyrazole or aminopyrazole with a picryl halide or picrylpyrazole. Some of these materials could be nitrated under carefully controlled conditions to the corresponding nitropyrazole derivatives. The products were identified by n.m.r. spectroscopy, and their crystal densities and thermal stabilities were determined. Drop-weight impact sensitivities were measured for some of the more interesting compounds.     

Nitro derivatives of 1-picrylbenzotriazole

The synthesis of the isomeric 4,6-, 5,6-, and 5,7-dinitro-1-picrylbenzotriazoles has been accomplished. The nmr spectra of these compounds and the mononitro derivatives of 1-picrylbenzotriazole were determined and the substituent effects of the nitro and picryl groups on the chemical shifts of the various benzotriazole protons are discussed.     

1,3-Dipolar cycloadditions of alkyl azides with picryl isothiocyanate:Isolation of stable monoadducts

Picryl isothiocyanate ( 4 ), prepared in a two-step sequence from picryl chloride ( 2 ), reacts smoothly with alkyl azides to yield 4-alkyl-5-picrylimino-1,2,3,4-thiatriazolines 5 which are stable below 100°. These adducts combine with isocyanates in a bimolecular process with loss of nitrogen, similar to the formation of phenylimino derivatives but different from that of sulfonyliminothiatriazolines.     

Studies on medicinal resources from livestock. II. Anti-allergic effects of pig bile. (2)

Anti-allergic activities of lyophilized pig bile [( PB]) were examined in mice with picryl chloride-induced contact dermatitis (PC-CD), an experimental model of delayed-type hypersensitivity (DTH; type-IV allergy). PC-CD was markedly inhibited by an oral administration of [PB] within 4 h after but not during 8 to 16 h after challenge with picryl chloride. Anti-inflammatory activities of [PB] were also examined in acetic acid-induced mouse increased vascular permeability, hypotonic-hyperthermic lysis of rat erythrocytes and carrageenin-induced rat hind paw edema. [PB] had no effect on these models. The present study suggests that [PB] inhibits PC-CD through its immuno-modulation in the inductive phase of DTH rather than by an anti-inflammatory action.     

Reactions of 2-aminopyridine with picryl halides

2-Aminopyridine reacts with picryl halides to give mixtures of 1-picryl-2-(N-picrylimino)-1,2-dihydropyridine and 2-(N-picrylamino)pyridine. When picryl fluoride is treated with an excess of 2-aminopyridine, the 1-picryl-2-(N-picrylimino)-1,2-dihydropyridine reacts further with 2-aminopyridine to yield two molecules of 2-(N-picrylamino)pyridine in a reaction catalyzed by the by-product, hydrogen fluoride. In contrast, the compositions of the mixtures obtained from the reactions of picryl chloride and picryl bromide with excess 2-aminopyridine are stable in their reaction media.     

Picryl derivatives of benzo[1,2-d:4,5-d′]bistriazole and benzo[1,2-d:4,5-d′]bistriazole-4,8-dione

In a previous communication from this laboratory it was reported that benzotriazole reacts with both picryl chloride and picryl fluoride to give 1-picrylbenzotriazole exclusive of any 2-picrylbenzotriazole (3). As an extension of this study we have examined the reactions of benzo[1,2-d:4,5-d′]bistriazole (I) and benzo[1,2-d:4,5-d′]bistriazole-4,8-dione (II) with picryl fluoride.     

Picrylamino-substituted heterocycles. III. 1,2,4-triazoles

This paper describes the synthesis of various picryl-and picrylamino-substituted 1,2,4-triazoles and 3,3′-bi-1,2,4-triazolyls. These compounds were prepared by condensing the appropriate 1,2,4-triazole or amino-1,2,4-triazole with a picryl halide. The proton n.m.r. spectra, crystal densities, thermal stabilities, and drop-weight impact sensitivities of the resulting compounds were determined.     

Synthesis of pyrimidine derivatives possessing an antioxidative property and their inhibitory effects on picryl chloride-induced contact hypersensitivity reaction

We conducted a preliminary structure-activity relationship (SAR) study of some barbituric acid and uracil derivatives against the picryl chloride-induced contact hypersensitivity reaction. The introduction of an antioxidative moiety to the side chain of the C(6)-position of uracil was effective against this model. The introduction of dimethoxyphenol (8b) or dimethylphenol (8c) instead of di-t-butylphenol (8a) as an antioxidative moiety gave diminished activities, so, the reactive oxygen would contribute to the inflammation of this model, and an antioxidative activity was required for exhibiting the inhibitory activity. The inhibitory activity was significantly affected by the substituent at the N(1)-phenyl moiety.     

Inhibitory activities of novel pyrimidine derivatives on the contact hypersensitivity reaction

In order to obtain novel topically applied anti-inflammatory compounds containing an inexpensive anti-oxidative moiety without chirality, we synthesized compound 2c derivatives having a di-tert-butylphenol moiety, and evaluated by topical administration their anti-inflammatory potentials on picryl chloride-(PC) induced contact hypersensitivity reaction (CHR) in mice. In the course of our structure-activity relationship (SAR) studies on the pyrimidine or the anti-oxidative moiety and the linker between them, the most potent compounds (10, 11) were obtained by the insertion of a C2 unit in compound 2c. The potencies of these compounds were 2-fold greater than that of 1. Compounds 10 and 11 were considered to be useful lead compounds having inexpensive anti-oxidative moieties without chirality.     

Investigation of energetic materials prepared by reactions of diamines with picryl chloride

Five compounds containing picryl group(s) were synthesized from reactions of hydrazine, 1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane and 1,7-diaminoheptane with picryl chloride under hydrothermal conditions in methanol. Hydrazine reaction yielded N-2,4,6-trinitrophenylhydrazine which has a single picryl group, whereas the other reactants formed symmetric products with both amine groups connected to picryl groups. These compounds are N,N′-di-2,4,6-trinitrophenyl-1,2-diaminoethane, bis-N,N′-di-2,4,6-trinitrophenyl-1,3-diaminopropane, bis-N,N′-di-2,4,6-trinitrophenyl-1,4-diaminobutane and bis-N,N′-di-2,4,6-trinitrophenyl-1,7-diaminoheptane. Molecular structures of two of these compounds, N-2,4,6-trinitrophenylhydrazine and bis-N,N′-di-2,4,6-trinitrophenyl-1,3-diaminopropane, were revealed by XRD methods. All compounds were investigated by TG and DSC methods. The thermal behaviour of N-2,4,6-trinitrophenylhydrazine was explosive, undergoing a strong explosion in a very short temperature interval, 180–185 °C. In cases of the other compounds, it was found out that the carbon chain between two picryl groups reduced the explosion enthalpy. In addition, the theoretical formation enthalpy of N-2,4,6-trinitrophenylhydrazine was calculated by running CBS-4 M energy calculations under Gaussian 09 software package. From the calculated value, reaction enthalpy values for the possible explosion pathways were investigated in accordance with the experiment. The path with reaction enthalpy closest to the experimental value was proposed as the explosion mechanism.     

Studies on medicinal resources from livestock. I. Anti-allergic effects of pig bile. (1)

Anti-allergic activities of animal biles and commercially available bile acids were evaluated in experimental allergic disease models. Pig bile exhibited marked preventive effects on the models of delayed-type hypersensitivity (type IV allergy), picryl chloride-induced contact dermatitis (PC-CD) and sheep red blood cells (SRBC)-induced footpad swelling in mice. Fel ursi (dried bear gallbladder) also had an inhibitory effect on PC-CD, whereas ox bile, chicken bile and bile acids had no effect on ether of the models.     

New N-aryloxy-phthalimide derivatives. Synthesis,physico-chemical properties,and QSPR studies

Starting from N-hydroxyphthalimide 1 and the reactive fluoro- or chloro-nitroaryl derivatives 2, 3 and 4a-e (2-chloro-3,5-dinitropyridine; 3, NBD-chloride; 4a, 1-fluoro-2,4-dinitrobenzene; 4b, picryl chloride; 4c, 4-chloro-3,5-dinitrobenzotrifluoride; 4d, 2-chloro-3,5- dinitrobenzotrifluoride; 4e, 4-chloro-3,5-dinitrobenzoic acid) the corresponding N-(2-nitroaryloxy)-phthalimide derivatives 5a-e, or 6 and 7 were obtained and characterized by IR, UV-Vis ¹H-NMR and ¹³C-NMR spectroscopy. The TLC behavior and the hydrophobicity of these derivatives have been experimentally evaluated by R_M0 parameters (using RP-TLC). The experimental R_M0 parameters were compared with the calculated partition coefficient, log P. A QSPR study was also performed to establish possible correlations between the structure and physical properties (λ_max and R_M0) of compounds 5a-e, 6, and 7.      

Synthesis and testing of 2-deoxy-2,2-dihaloglycosides as mechanism-based inhibitors of alpha-glycosidases

The synthesis of a series of 2-deoxy-2,2-dihaloglycosyl halides as potential alpha-glycosidase inactivators has been achieved via the halogenation of protected 2-fluoroglycal precursors. Direct chlorination of per-O-acetylated 2-fluoro-d-glucal and 2-fluoromaltal followed by basic deprotection yielded the corresponding 2-chloro-2-deoxy-2-fluoroglycosyl chlorides. Reaction of the per-O-acetylated 2-fluoroglycals with acetyl hypofluorite or Selectfluor yielded the 2-deoxy-2,2-difluoroglycosyl derivatives, which were converted to their alpha-chlorides using thionyl chloride and deprotected under basic conditions. Trinitrophenyl glycosides of the 2-deoxy-2,2-difluoro mono- and disaccharides were synthesized by arylation of the hemiacetals with picryl fluoride, then deprotected with HCl in methanol. All three monosaccharide derivatives caused active site-directed, time-dependent inactivation of yeast alpha-glucosidase via the trapping of covalent glycosyl-enzyme intermediates, and kinetic parameters for inactivation by each compound were determined. Surprisingly neither of the 2-deoxy-2,2-dihalomaltosyl chlorides caused time-dependent inactivation of human pancreatic alpha-amylase, despite the fact that the trinitrophenyl 2-deoxy-2,2-difluoromaltoside functioned in that mode. The trinitrophenyl glycosides appear to be approximately 1000-fold more reactive than the corresponding chlorides in the enzyme active sites.     

Intramolecular Charge Transfer Complexes. 4. Poly(N-(2-hydroxyethyl)carbazolyl Acrylate-co-Picryl Methacrylate)

Abstract

Radical copolymerization of N-(2-hydroxyethyl)carbazolyl acry-late with picryl methacrylate takes place mainly through the inter-monomeric charge transfer complex (CTC) in dioxane solution. When the solvent is 1, 2-dichloroethane, concurrent chain transfer reactions arise. The copolymers obtained are intramolecular CTC. The charge transfer interaction depends on copolymer composition and conformation, and on the copolymerization solvent.     

Synthesis, structure, spectral, and electrochemical properties of the Au(I) complex with 5-methoxy-8-(N-picrylamino)quinoline

The synthesis of a gold(I) chelate complex obtained from an autocomplex of the picryl series with a quinoline-containing donor fragment is described. The crystal structure was established by X-ray analysis, the spectral and electrochemical properties were studied. The molecules of the complex obtained have a conformation in which both o-NO₂ groups of the picryl fragment participate in intramolecular charge transfer by contact.M. V. Lomonosov Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1028–1035, August, 1999.     

An Easy Access to Benzofurans via DBU Induced Condensation Reaction of Active 2‐Hydroxy Acetophenones with Phenacyl Chlorides: A Novel Class of Antioxidant Agents

A convenient and efficient one‐pot synthesis of benzofurans 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l , 3m , 3n , 3o , 3p , 3q , 3r , 3s , 3t has been described from 2‐hydroxy acetophenones and phenacyl chlorides in the presence of DBU. The procedure was applicable for a variety of phenacyl chlorides and provides a variety of benzofurans with higher yields. DBU acts as a base and as well as nucleophiles. All the derivatives were subjected to in vitro antioxidant screenings against representative 2,2′‐diphenyl‐1‐picryl‐hydrazyl and 2,2′‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid) radicals and results worth for further investigations.