Synthesis, structure and complexation of the fluorinated 1,3-enaminoketones containing at the nitrogen atom substituents with a terminal C≡C bond

The reaction of fluorinated lithium 1,3-diketonates with propargylamine hydrochloride and 1,1,1-trifluorpentane-2,4-dione or 1,1,1-trifluoro-4-methoxypent-3-en-2-one with propargylamine and 3-aminophenylacetylene were performed to obtain fluorinated 1,3-enaminones containing at a nitrogen atom substituents with terminal C≡C bonds: (Z)-1,1,1-trifluoro-4-(2-propynylamino)-3-pentene-2-one, (Z)-1,1,2,2-tetrafluoro-5-(2-propynylamino)-4-hexen-3-one, and 4-(3-ethynylphenylamino)-1,1,1-trifluoropentyl-3-en-2-one. Reactions of 4-(3-ethynyl-phenylamino)-1,1,1-trifluoro-pentyl-3-en-2-one with Cu(II) acetate or nanosized powder of copper or its oxides led to the respective chelate complex. The structure of (Z)-1,1,2,2-tetrafluoro-5-(2-propynylamino)-4-hexen-3-one and a copper complex of 4-(3-etinilphenylamino)-1,1,1-trifluoropenta-3-en-2-one was determined by XRD.     

Catalysis of copper(II) chelate-amine complexes in the oxidative coupling of 2,6-dialkylphenols

The oxidative coupling reaction of 2,6-dimethylphenol and 2,6-di-tert-butylphenol with molecular oxygen was performed by using a series of copper(II) chelate complexes as a catalyst, derived from copper(II), β-diketone, and some Shiff bases. Under the applied reaction conditions, the reaction products of 2,6-dimethylphenol were poly(2,6-dimethyl-1,4-phenylene oxide) (C? O coupling product) and 3,3′,5-5′-tetramethyl-4,4′-diphenoquinone (C? C coupling product), and that of 2,6-di-tert-butylphenol oxidation was only 3,3′,5-5′-tetra-tert-butyl-4,4′-diphenoquinone (C? C coupling product). The catalytic activity has been shown to be dependent on the properties of the copper(II) chelates used as catalysts and the mole ratios of amine ligand to copper(II) chelate (ligand ratio). The basicity and the steric bulkiness of the amine used as a ligand for copper(II) β-diketonato catalysts were found to be two of the main factors that govern the oxidative coupling mode (C? O and/or C? C coupling) of 2,6-dimethylphenol. The oxidative coupling activity of 2,6-dialkylphenol is discussed in terms of both the stabilities of the copper(II) chelates and of the copper(II) chelate-amine adducts. The rate of oxygen absorption for 2,6-dimethylphenol catalyzed by the copper(II) acetylacetonato-piperidine system is first order in oxygen partial pressure and zero order in 2,6-dimethylphenol concentration, respectively. A Cu(II)-oxygen, as an intermediate is suggested on the basis of the results obtained.     

A practical synthesis of pyoluteorin

A convenient, large-scale synthesis of the antibiotic pyoluteorin, 2,3-dichloro-5-(2′,6′-dihydroxybenzoyl)-pyrrole ( 1 ), is described. A key step in the synthesis involved a Friedel-Crafts aroylation of pyrrole with 2,6-dimethoxybenzoyl chloride ( 3 ) in methylene chloride. The desired intermediate, 2-(2′,6′-dimethoxybenzoyl)pyrrole ( 4 ), was obtained as the major product, along with a product of beta substitution ( 6 ). Compound 4 was converted to pyoluteroin ( 1 ) in four steps in an overall yield of 51%.     

Pyoluteorin derivatives. II. Synthetic approaches to pyrrole ring substituted pyoluteorins

A method for the regiospecific synthesis of 3-substituted 2-aroylpyrroles is described. These pyrroles, which are structurally related to the naturally occurring antibiotic pyoluteorin, are prepared by a Friedel-Crafts aroylation of 4-substituted pyrrole-3-carboxylic acid esters with 2,6-dimethoxybenzoyl chloride. The carboalkoxy group is then removed by hydrolysis and decarboxylation to produce isomerically pure 3-substituted-2-(2′,6′-dimethoxybenzoyl)pyrroles ( 5 and 13 ). Conversion of these pyrroles into pyoluteorin-like compounds led to some unexpected products which arise from facile cleavage of the dihydroxybenzoyl portion of the molecules during chlorination.     

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-D-glucitol

1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.     

2,3-Epoxyperfluoro-2-methylpentane in reactions with urea and thiourea

2,3-Epoxyperfluoro-2-methylpentane reacts with thiourea in protic (methanol, 2-propanol) and aprotic (dioxane) solvents, and also with urea in acetonitrile affording unexpected products: 1-(2,2,3,3,3-pentafluoropropionyl)-2-(2,2,2-trifluoro-1-trifluoro-methylethyl)isothiourea, and 1-(2,2,3,3,3-pentafluoropropionyl)-3-(2,2,2-trifluoro-1-trifluoro-methylethyl)urea respectively that result from the rearrangement of the intermediately formed ketone in the process of the intramolecular “haloform” cleavage. At the same time in dioxane the 2,3-epoxyperfluoro-2-methylpentane reacts with urea with the formation of a heterocyclic compound, 2-amino-4-pentafluoroethyl-5,5-bis(trifluoromethyl)-4,5-dihydrooxazol-4-ol. From 1-(2,2,3,3,3-pentafluoropropionyl)-2-(2,2,2-trifluoro-1-trifluoromethylethyl)isothiourea and Cu(OAc)₂ a stable fluorine-containing chelate complex was obtained.     

Enantiocontrolled synthesis of 2,6-disubstituted piperidines by desymmetrization of meso-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. application to the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine

A conceptually new approach to the enantiocontrolled synthesis of 2,6-disubstituted piperidines was achieved by desymmetrization of meso-2,6-dimethoxy-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. After protection of the piperidine nitrogen as a urethane derived from (+)- or (-)-trans-2-(alpha-cumyl)cyclohexyl (TCC), a sequential, one-pot methoxide abstraction/nucleophilic addition/methoxide abstraction/nucleophilic addition generated good yields of 2,6-disubstituted-eta-(3,4,5)-dihydropyridinylmolybdenum complexes. This sequence proceeds by way of a highly diastereoselective methoxide abstraction (>40:1). High yielding protodemetalation and N-deprotection provided a simple and enantiocontrolled synthetic entry to a variety of 2,6-disubstituted piperidines. This new method was used for the total synthesis of (-)-dihydropinidine and (-)-andrachcinidine.     

Oxidation of perfluoroaromatics

3,4,5,6-Tetrafluoro-2-nitroaniline (I), 2,3,5,6-tetrafluoro-4-nitroaniline (IV) and 2,5,6-trifluoro-4-nitro-1,3-phenylenediamine (VI) react with nitrous acid to give 3,4,5-trifluoro-6-nitro-1,2-diazo-oxide (III), 3,5,6-trifluoro-4-nitro-1,2-diazo-oxide and (V) 5-fluoro-6-nitro-bis-1,2:3,4-diazo-oxide (VII), respectively. Reduction of the diazo-oxide (III) with hypophosphorous acid gives 4,5,6-trifluoro-3-nitrophenol (VIII). Treatment of 2,3,4,6-tetrafluoroacetanilide with nitric acid affords trifluoro-p-benzoquinone (X), the reduction of which gives trifluorohydroquinone (XI). Proton and fluorine chemical shifts and coupling constants of the new compounds are reported.     

Synthesis of 4-hydroxy- and 3-aryl-4-amino- 2-trifluoromethylpyridines

Schemes for synthesizing 3-acyl-4-amino(hydroxy)-2-trifluoromethylpyridines from 3-acyl 4-amino-5,5,5-trifluoro-3-penten-2-ones via their diphenylboron chelate complexes have been suggested.Translated fromlzvestiyn Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2715–2718, November, 1996,     

Features of reactions of polyfluorinated ethyl 4-oxo-2-pnenyl-4H-chromene-3-carboxylates with N-nucleophiles

Ethyl 5,6,7,8-tetrafluoro-4-oxo-2-phenyl-4H-chromene-3-carboxylate in reactions with primary amines is characterized by a chromone-coumarin rearrangement affording 3-[amino(phenyl)methylene]-6,7,8-trifluoro-2H-chromene-2,4(3H)-diones, and ethyl 4-oxo-2-phenyl-5,6,7,8-tetrafluoro-4H-chromene-3-carboxylate characteristically adds the amine at the C² site of the flavone furnishing 3-amino-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylates which depending on the substituent at the amino group are capable of intramolecular cyclization into 3-[(alkylamino)(phenyl)methylene]-5,6,7,8-tetrafluoro-2H-chromene-2,4(3H)-dione or in the case of benzylamine substituent, into ethyl 1-benzyl-5-hydroxy-4-oxo-2-phenyl-6,7,8-trifluoro-1,4-dihydroquinoline-3-carboxylate. The main process in the reaction of tri- and tetrafluoroflavones with secondary amine (1-methylpiperazine) is the nucleophilic substitution at the C⁷ of flavone. In the reaction with 1,2-phenylenediamine 3-[(2-aminophenyl)amino]-3-phenyl-2-(2,3,4,5-tetrafluoro-6-hydroxybenzoyl)acrylate was obtained from tetrafluoroflavone and 1H-benzimidazol-2-yl(3,4,5-trifluoro-2-hydroxyphenyl)methanone, from trifluoroflavone.     

2,4,6-tris(methylsulfonyl)-3,5-dichloropyridine

The reactions of 2,6-bis(methylthio)-3,4,5-trichloropyridine and its N-oxide with sodium hydrosulfide were studied. A method for the synthesis of 2,4,6-tris(methylsulfonyl)-3,5-dichloropyridine was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3. pp. 369–371, March, 1976.     

Gravimetric determination of uranium(VI) with pyridine-2,6-dicarboxylic acid

Uranium(VI) can be quantitatively precipitated from aqueous solution in the pH range 2.1-6.9 with pyridine-2,6-dicarboxylic acid in the presence of tetraphenylarsonium chloride. This provides a new rapid gravimetric method for uranyl ion as an organic chelate complex of high molecular weight. Sodium, aluminium, copper and nickel as well as nitrate, chloride, sulphate and acetate ions, do not interfere, but iron(III) and thorium(IV) do.     

Extraction of copper(II) with the APCD/DIBK system from concentrated hydrochloric and nitric acid media: estimation of true limit of acidity for the extraction

The extraction of copper(II) from strongly acidic solution (0.01-8M hydrochloric and 0.01-5M nitric acid) with ammonium 1-pyrrolidinecarbodithioate in di-isobutyl ketone has been studied. Compared with the hydrochloric acid system, a considerably larger amount of the reagent is needed for complete extraction of copper chelate from nitric acid solution as the extract is more unstable in the nitric acid system. The decomposition of copper chelates extracted from nitric acid is based on the oxidation of the reagent and the chelate; the spectral change of the extract from nitric acid suggests that the copper(II) chelate is initially oxidized to copper(II) and then decomposes. The upper limit of the acidity of both acids from which the copper chelate can be quantitatively extracted strongly depends on the reagent concentration; the limit with 8 x 10(-2)M APCD (500-fold reagent: metal molar ratio) was taken as 8 and 4M for hydrochloric and nitric acid, respectively.     

Studies on the Extractive Constituents of the Nutmeg of Myristica Fragrans Houtt

From the hexane extractive of the nutmeg of Myristica fragrans Houtt, glyceryl trimyristate (1), myristicin (11), methyleugenol (12), elemicin (13), dehydrodiisoeugenol (9), 1-(3,4,5-trimethoxyphenyl)-2-(4-allyl-2,6-dimethoxyphenoxy)-propan-1-ol (4), 1-(3,4-methylenedioxyphenyl)-2-(4-allyl-2,6-dimethoxyphenoxy)-propan-1-ol (6), and a new compound 1-(3,4-dimethoxyphenyl)-2-(4-allyl-2,6-dimethoxyphenoxy) propan-1-ol (14) were isolated. The structure of compound (14) was determined to be an analogue of the β-0-4 ether type of dilignols.     

Trifluoromethyl substituted 4-pyrones via self-condensation of trifluoroacetoacetates

When 3-(acetoxy)-4,4,4-trifluoro-2-butenoates 7 and 8 are heated at 100°, in the presence of catalytic amounts of zinc chloride, they undergo self-condensation to yield 2,6-bis(trifluoromethyl)-4-pyrones 1 and 2 respectively. Compounds 1 and 2 were further converted to the corresponding pyridine derivatives 3 and 4 via ammoniolysis.     

Synthesis of α-(4-hydroxyphenyl)-β,β,β-trifluoro-α-alanine derivatives

2,6-Dimethyl- and 2,6-dimethoxy-α-methoxycarbonyl-α-trifluoromethyl-p-methylenequinones have been synthesized. These compounds easily react with ammonia, morpholine, andp-toluidine to afford the corresponding α-(4-hydroxyphenyl)-β,β,β-trifluoro-α-alanine derivatives.     

The application of salicylaldoxime in solvent extraction : Part II. Spectrophotometric determination of copper with 2-(5-nitro-2-pyridylazo)-1-naphthol after separation with salicylaldoxime

A highly sensitive spectrophotometric method for the determination of traces of copper with 2-(5-nitro-2-pyridylazo)-l-naphthol (5N-α-PAN) has been developed. At a pH of 3–4copper(II) is selectively extracted into chloroform as its salicylaldoxime chelate and then stripped into an aqueous acid solution; the pH is adjusted to 9.3, and 5N-α-PAN is added. The 1:2 chelate between copper(II) and the reagent, which promptly precipitates, is extracted into chloroform and measured at 598 nm. The molar absorptivity is 86,000. The application of the method to the analysis of high-purity magnesium and cobalt is described.     

Chelate synthesis of 3-ethoxycarbonyl-4-hydroxy-2-trifluoromethylpyridine from ethyl acetoacetate and trifluoroacetonitrile

Ethyl 2-acetyl-3-amino-4,4,4-trifluoro-2-butenoate was synthesized by treatment of ethyl acetoacetate with CF₃CN in the presence of Ni(acac)₂. Condensation of the diphenylboron chelate of the former with dimethylformamide dimethylacetal followed by refluxing in ethanol yielded 3-ethoxycarbonyl-4-hydroxy-2-trifluoromethylpyridine.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1329–1331, July, 1995.This study was financially supported by the Russian Foundation for Basic Research (Grant No. 94-03-08964).     

A new expedient route to 2,6-diaryl-3-cyano-4-(trifluoromethyl)pyridines

1-Aryl-4,4,4-trifluoro-1,3-butanediones 1 react with β-amino-β-arylacrylonitrile 2 , readily available from acetonitrile with aryl nitriles in the presence of potassium t-butoxide, to afford the corresponding 2,6-diaryl-3-cyano-4-(trifluoromethyl)pyridines 3 in moderate to excellent yields.     

New pyridine carboxamide ligands and their complexation to copper(II). X-Ray crystal structures of mono-, di, tri- and tetranuclear copper complexes

Seven new pyridine dicarboxamide ligands H2L(1-7) have been synthesised from condensation reactions involving pyridine-2,6-dicarboxylic acid (H2dipic), pyridine-2,6-dicarbonyl dichloride or 2,6-diaminopyridine with heterocyclic amine or carboxylic acid precursors. Crystallographic analyses of N,N'-bis(2-pyridyl)pyridine-2,6-dicarboxamide monohydrate (H2L8 x H2O), N,N'-bis[2-(2-pyridyl)methyl]pyridine-2,6-dicarboxamide and N,N'-bis[2-(2-pyridyl)ethyl]pyridine-2,6-dicarboxamide monohydrate revealed extensive intramolecular hydrogen bonding interactions. 2,6-Bis(pyrazine-2-carboxamido)pyridine (H2L6) and 2,6-bis(pyridine-2-carboxamido)pyridine (H2L7) reacted with copper(II) acetate monohydrate to give tricopper(II) complexes [Cu3(L)2(mu2-OAc)2]. X-Ray crystallography confirmed deprotonation of the amidic nitrogen atoms and that the (L6,7)2- ligands and acetate anions hold three copper(II) ions in approximately linear fashion. H2L8. Reacted with copper(II) tetrakis(pyridine) perchlorate to give [Cu(L8)(OH2)]2 x 2H2O, in which (L8)2- was tridentate through the nitrogen atoms of the central pyridine ring and the deprotonated carboxamide groups at one copper centre, with one of the terminal pyridyl rings coordinating to the other copper atom in the dimer. The corresponding reaction using H2L7 gave [Cu3(L7)2(py)2][ClO4]2, which transformed during an attempted recrystallisation from ethanol under aerobic conditions to a tetracopper(II) complex [Cu4(L7)2(L7-O)2].