Picrylamino-substituted heterocycles. V. pyridines

The condensation of various aminopyridines with picryl chloride and picryl fluoride has been investigated as part of our continuing effort in the field of picrylamino-substituted heterocycles. In addition to the expected picrylamino derivatives we obtained the 1-picryl derivatives of the imino forms of some of the amines.     

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.     

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.     

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.     

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.     

Aminolysis of methoxy groups in pyrimidine derivatives. Activation by 5‐nitroso

The nucleophilic substitution of 2‐mefhoxy groups in pyrimidine derivatives was strongly activated by introduction of a 5‐nitroso group on to the pyrimidine ring. The aminolysis of several 2‐methoxy‐5‐nitrosopyrimidine derivatives was performed at room temperature in hydroxylic as well as in non‐hydroxylic media with different primary amines in short time and good yields. The aminolysed substrates include 6‐[(per‐O‐acetyl)glycosyl]aminopyrimidines which afforded the corresponding 2‐aminopyrimidines without harming the acetyl protecting groups of the sugar moiety.     

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.     

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.     

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.     

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.     

Cationic Polymerization of β-Phenylvinyl Alkyl Ethers

Abstract

The cationic polymerization of β-phenylvinyl alkyl ethers (alkyl: methyl, ethyl, n-propyl, and n-butyl) was examined in toluene and in methylene chloride with boron fluoride etherate and with stannic chloride at ?78°C. Despite the fact that these monomers have bulky substituents on the α –and β-carbons, they could be homopoly-merized easily even in nonpolar sovent at ?78°C. The general features of β-phenylvinyl alkyl ethers in homopolymerization and co-polymerization with n-butyl vinyl ether suggested that β-phenylvinyl alkyl ethers behaved as derivatives of vinyl ethers, not as derivatives of styrenes. The polymerization products were white powders having a high softening point.     

Perfluorophenyl derivatives of the elements XXVIII. Some reactions of fluoro-aromatic acetylenes

Reactions between caesium fluoride, bromine, palladium chloride, triiron dodecacarbonyl, dicobalt octacarbonyl, nickelocene, cyclopentadienylmanganese tricarbonyl or decarborane with, acetylenes containing one highly fluorinated aromatic group are described. The products mainly resembled those obtained from analogous experiments involving diphenylacetylene, although in the case of the PdCl₂ reaction no intermediate derivatives could be isolated.     

S-and Se-dimethylarsino derivatives of thio- and selonopyrimidines and purines

The synthesis of dimethylarsinothio-and dimethylarsinoselonopyrimidines and -purines which utilizes diethylaminodimethylarsine is described. A series of these derivatives, with different substituents on the heterocyclic ring, has been investigated by infrared, nmr, and mass spectroscopic methods. Attempts to prepare O-or N- arsinous acid derivatives from oxy- and aminopyrimidines were unsuccessful.     

Hydroxide-catalyzed synthesis of heterocyclic aromatic amine derivatives from nitriles

A generalized method for synthesizing a wide variety of heterocyclic aromatic amine derivatives from nitriles by use of hydroxide catalysts is presented. Nitrile dimers (3-aminocrotononitrile and dicyandiamide) and a dimer analog (anthranilonitrile) react with monomeric nitriles in the presence of hydroxide to form respectively, aminopyrimidines, diaminotriazines and aminoquinazolines.     

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.     

N-Arylsulfonyl-N′-pyrimidinylsubstituierte Chloralaminale

N-Arylsulfonyl-N-pyrimidinyl substituted aminals of chloral were prepared from N-(1-Hydroxy-2,2,2-trichloroethyl)arylsulfonamides with thionyl chloride and subsequent reaction with aminopyrimidines.

     

Acetylenic ketones. Part III . Reaction of acetylenic ketones with nucleophilic sulfur compounds

Aroylphenylacetylenes reacted with ammonium dithiocarbamate and ammonium hydrogen sulfide in 60% dioxane-waler mixture at 15° to give mainly a mixture of the corresponding β-hydroxy-α-thiobenzoylstyrene derivatives (III) and (E,Z)-β,β'-di(α-aroylstyryl) sulfides (IV), whereas with sodium xanthate and sodium sulfide they gave only (III). However, when benzoyl-(Ia) or p-ehlorobenzoyl-(Id)phenylacetylenes was refluxed with ammonium dithiocarbamate in ethyl alcohol, it gave a mixture of (IIIa or d) and the (E,E)-β,β'-di(α-aroylstyryl) sulfide (VIa or d). β-Hydroxy-α-thiobenzoylstyrene derivatives (III), (E,Z)-(IV) and (E,E)-(VI)-β,β'-di(α-aroylstyryl) sulfides reacted with hydrazine hydrate and phenylhydrazine to give 3(5)-aryl-5(3)-phenyl-(IX)- and 5-aryl-1,3-diphenyl-(X)pyrazoles, respectively. The former compounds (III) reacted with guanidine and ethyl hydrazinecarboxylate to give the corresponding aminopyrimidines (XIII) and acetophenone-N-ethoxycarbonyl hydrazones (XI), respectively.     

An Efficient Synthesis of Pyrido[2,3‐d][6,5‐d]dipyrimidine and 5,5′‐Arylmethylenebis(2,6‐diaminopyrimidinone) Derivatives under Microwave Irradiation

A series of pyrido[2,3‐d][6,5‐d]dipyrimidine and 5,5′‐arylmethylenebis(2,6‐diaminopyrimidinone) derivatives have been synthesized through a rapid reaction of aromatic aldehydes with aminopyrimidines in acetic acid under microwave irradiation. This method has the advantages of simple operation, high yields, short reaction time, and easy work‐up.     

Al(OTf)3-catalyzed one-pot synthesis of pyrrolo[3,2-d]pyrimidinedione derivatives

A series of polysubstituted pyrrolo[3,2-d]pyrimidinedione derivatives have been synthesized in excellent yields. This prominent scaffold is obtained via an Al(OTf)₃-catalyzed tandem addition-annulation sequence between propargylic alcohols and aminopyrimidines. The process is simple, facile, inexpensive, and provides a diverse range of substituted pyrrolo [3,2-d]pyrimidinedione derivatives with short reaction times from readily obtainable starting materials.     

UV exposure alters respiratory allergic responses in mice

We have tested the hypothesis that exposure to ultraviolet light would inhibit T helper-1 (Th1) responses and stimulate T helper-2 (Th2) responses, and that thus in a mouse model of allergic (i.e. extrinsic) asthma (using ovalbumin [OVA] as the allergen) increased symptoms would be observed, while in a model of Th1-dependent occupational asthma (in which picryl chloride is the allergen) decreased symptoms would be observed. Whereas reduced interferon (IFN)-gamma production, decreased inflammatory responses in the airways, and reduced airway reactivity to nonspecific stimuli were observed in UV-preexposed picryl chloride sensitized and challenged mice, the results in the OVA model were less clear. Increased interleukin (IL)-10 production as a result of UV exposure was observed, together with unchanged IL-4 and IFN-gamma. In addition, decreased OVA-specific immunoglobin, IgG1 and IgE, titers were noted, as well as decreased nonspecific airway hyperreactivity. Eosinophilic inflammatory responses were not influenced. The results indicate that UV exposure can have systemic effects that influence ongoing immune responses in the respiratory tract. The effects are not only restricted to immune responses that are predominantly Th1 dependent (i.e. pulmonary delayed-type hypersensitivity and IFN-gamma production in response to picryl chloride) but also to immune response that are predominantly Th2 dependent, i.e. decreased specific IgE titers.