A simple and convenient synthesis of 4-methyl-3-nitro-2-trihalomethyl-2H-chromenes from N-unsubstituted imines of 2-hydroxyacetophenones and trichloro(trifluoro)ethylidene nitromethanes

The reaction of N-unsubstituted imines of 2-hydroxyacetophenones with trichloro(trifluoro)ethylidene nitromethanes in the presence of DABCO proceeds via tandem oxa-Michael/aza-Henry additions (in dichloromethane) or aza-Michael addition (in benzene) to give 4-methyl-3-nitro-2-trichloro(trifluoro)methyl-2H-chromenes or 1,1,1-trichloro(trifluoro)-3-nitro-N-[1-(2-hydroxyaryl)ethylidene]propan-2-amines, respectively.     

Domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylalkylidene)malononitriles: synthesis of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans and a rare case of [1,5] sigmatropic shift of the nitro group

A variety of functionalized 6-(trifluoromethyl)-6H-dibenzo[b,d]pyrans were easily synthesized in good yields under mild conditions by a domino reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with 2-(1-phenylethylidene)- and 2-(1-phenylpropylidene)malononitriles. In the latter case, intermediate 7-amino-10-methyl-10-nitro-9-phenyl-6-(trifluoromethyl)-10,10a-dihydro-6H-benzo[c]chromene-8-carbonitriles were isolated as a result of a rare [1,5] sigmatropic shift of the nitro group.     

Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity.     

Nitropyrazoles 22. On reactivity of 3,5-dinitro-4-(phenylsulfonyl)pyrazole and its N-methyl derivative

3,5-Dinitro-4-(phenylsulfonyl)pyrazole (5) obtained by oxidation of 3,5-dinitro-4-(phenylthio)pyrazole with 30% H₂O₂ in AcOH was involved into nucleophilic substitution reaction with thiophenol, which proceeded with substitution of the phenylsulfonyl group at position 4. N-Methyl-3,5-dinitro-4-(phenylsulfonyl)pyrazole obtained by methylation of 5 with dimethyl sulfate was involved into nucleophilic substitution reaction with thiophenol, p-bromophenol, and morpholine with the regioselective substitution of the nitro group at position 5 to form 5-R-3-nitro-4-(phenylsulfonyl)pyrazoles.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

A simple synthesis of the pentacyclic lamellarin skeleton from 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl(benzyl)-3,4-dihydroisoquinolines

The basic structural framework of lamellarin alkaloids, 8,9-dihydro-6H-chromeno[4′,3′:4,5]pyrrolo[2,1-a]isoquinoline derivatives, has been obtained in good yields via Grob synthesis between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-methyl-3,4-dihydroisoquinolines in refluxing isobutanol. In the case of 1-benzyl-3,4-dihydroisoquinolines, a dynamic NMR effect was observed in the ¹H and ¹⁹F NMR spectra of the products as a result of restricted rotation about the single bond linking the benzene ring and the heterocyclic system. When the reaction was carried out with 3-nitro-2-(trichloromethyl)-2H-chromenes in toluene at room temperature, only Michael adducts, as a mixture of two diastereomers, were isolated.     

Reactions of 3-nitro-2-trihalomethyl-2H-chromenes with C-nucleophiles. Synthesis of 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes

The nucleophilic addition of acetylacetone and ethyl acetoacetate at the double bond of 3-nitro-2-trihalomethyl-2H-chromenes in the presence of NaH affords 2,3,4-trisubstituted chromanes containing the β-dicarbonyl fragment at position 4. The trans-trans configuration and the enol structure of the reaction products were confirmed by ¹H NMR spectroscopy and X-ray diffraction. Treatment of these compounds with hydrazine gives the corresponding 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes. The reactions of 3-nitro-2-trihalomethyl-2H-chromenes with nitromethane and nitroethane in the presence of K₂CO₃ produce 1,3-dinitro derivatives of the chromane series. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1945–1955, November, 2006.     

A facile route to the pentacyclic lamellarin skeleton via Grob reaction between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1,3,3-trimethyl-3,4-dihydroisoquinolines

The basic structural framework of lamellarin alkaloids, 8,9-dihydro-6H-chromeno[4′,3′:4,5]pyrrolo[2,1-a]isoquinoline derivatives, has been obtained in good yields via Grob reaction between 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1,3,3-trimethyl-3,4-dihydroisoquinolines in refluxing isobutanol. When the reaction was carried out in toluene at room temperature, only Michael adducts, as a mixture of two diastereomers, were isolated.     

The reaction of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones with dinucleophilic reagents: a convenient route to fluoroalkylated nitrogen-containing tricyclic compounds

The reactions of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones (2) with hydrazine hydrate and phenyl hydrazine were investigated. The reaction of 2 with hydrazine hydrate in ethanol under reflux condition readily gave 2-fluoroalkyl-4H-pyrazolo[5,1-b]quinazolin-9-ones (3) in high yields. The reaction of 2 with phenyl hydrazine, however, resulted in the formation of 2-(2-phenyl-5-fluoroalkyl-2H-pyrazol-3-yl) benzoic acids (7). Further treatment of 7 with PPA gave 1-phenyl-4,9-dihydro-3-fluoroalkyl-1H-pyrozolo[3,4-b]quinolin-4-ones (4) in 65-80% overall yields.     

α-(3-Pyridyl)malonates: preparation and synthetic applications

Alkylation of aromatic rings is a major challenge in organic syntheses since more complex carbon skeletons can be constructed. The alkylation of pyridine by nucleophilic aromatic substitution of the nitro group in methyl 3-nitro-4-pyridylcarboxylate (1) with malonic ester is reported. The versatility of the α-(3-pyridyl) malonic ester product (3) is demonstrated by the formation of a number of new 3-alkylated pyridines and new fused bis-heterocycles. cis 2-Halomethyl-4-(3-pyridyl)tetrahydrofuran products were selectively prepared. Exact ¹H and ¹³C NMR assignments of practically all products were obtained by a series of NMR experiments.     

The substituent effect on mesomorphic properties of 4-octyloxyphenyl 4-(4-R-3-nitrobenzoyloxy)benzoates and 4-(4-octyloxybenzoyloxy)phenyl 4-R-3-nitrobenzoates

Abstract

The thermal properties of 4-octyloxyphenyl 4-(4-R-3-nitrobenzoyloxy) benzo-ates (1) and 4-(4-octyloxybenzoyloxy)phenyl 4-R-3-nitrobenzoates (2) have been examined, where R = hydrogen, halogens, alkyl and alkoxy groups. The derivatives of compound 1 incorporating hydrogen, halogens, methoxy and nitro groups show a smectic A phase having a bilayer arrangement, and the others with a long alkoxy group show the S_A phase with the monolayer arrangement. The derivatives of compound 2 incorporating halogens, and the nitro group show the S_A phase with the monolayer arrangement. The alkoxy derivatives show a smectic C phase as well as the nematic phase. The nitro group at the lateral position tends to increase the ratio of the S_A-N transition temperature to the N-I. The effect of the nitro group on the smectic properties has been discussed in terms of the structural and electrostatic nature of the nitro group.     

Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid

A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is, 4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-2H-chromene.     

Synthesis and reactivity of 2-polyfluoroalkylchromene-4(4<Emphasis Type="Italic">H</Emphasis>)-thiones

2-Polyfluoroalkylchromene-4(4H)-thiones, synthesized from 2-polyfluoroalkylchromones and P₂S₅, react with aniline, phenylhydrazines, and hydroxylamine at the C(4) atom and afford corresponding anils, phenylhydrazones, and oximes of chromones. On heating in alcohol in the presence of concentrated HCl, chromone phenylhydrazones and oximes undergo ring closure to form 3-(2-hydroxyaryl)-1-phenyl-5-polyfluoroalkylpyrazoles and 5-hydroxy-3-(2-hydroxyaryl)-5-polyfluoroalkyl-Δ²-isoxazolines.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2188–2195, October, 2004.     

Studies on the reduction of the nitro group in 3-aryl-2-methylene-4-nitro-alkanoates afforded by the Baylis-Hillman adducts: synthesis of 4-aryl-3-methylene-2-pyrrolidinones and 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylates

The formation of substituted 2-pyrrolidinones and indoles by the reduction of the secondary nitro group in appropriate 3-aryl-2-methylene-4-nitroalkanoates afforded by Baylis-Hillman chemistry via different reducing agents is described. The 3-aryl-2-methylene-4-nitroalkanoate obtained from S_N2 nucleophilic reaction between the acetate of Baylis-Hillman adducts and ethyl nitroacetate upon reduction with indium-HCl furnishes a mixture of cis and trans substituted phenyl-3-methylene-2-pyrrolidinones. In contrast, similar reductions of analogous substrates derived from nitroethane stereoselectively furnished only the trans substituted phenyl-3-methylene-2-pyrrolidinones. On the other hand the SnCl₂·2H₂O-promoted reductions of substrates derived from nitro ethylacetate give oxime derivatives while the ones obtained from nitroethane yield a mixture of cis and trans 4-aryl-3-methylene-2-pyrrolidinones. Alternatively, the SnCl₂·2H₂O-promoted reduction of substituted 2-nitrophenyl-2-methylene-alkanoate furnished from ethyl nitroacetate yield 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylate while indium-promoted reaction of this substrate leads to a complex mixture. Analogous reactions with SnCl₂·2H₂O of substituted 2-nitrophenyl-2-methylene-alkanoate obtained from nitroethane yield 4-alkyl-3-methylene-2-quinolones in moderate yields.     

3-nitro- and 3-bromo-3-nitroacrylates in reactions with phenyl azide

1,3-Dipolar cycloaddition of alkyl 3-nitro-and 3-bromo-3-nitroacrylates to phenyl azide gives regioisomeric alkyl 5(4)-nitro-1-phenyl-4,5-dihydro-1H-1,2,3-triazole-4(5)-carboxylates, the corresponding triazoles both with and without nitro group, and alkyl 3-nitro-1-phenylaziridine-2-carboxylates. Nitrotriazolecarboxylates were found to lose the ester moiety during chromatographic separation of the products on aluminum oxide. The structure of the products was determined on the basis of IR, ¹H NMR, and X-ray diffraction data.     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.     

Electronic effects in dianion radicals of nitro derivatives of 2-phenylbenzimidazole

The EPR spectra of the dianion radicals of 5(6)-nitro-2-(4-aminophenyl)benzimidazole (I), 5(6)-nitro-2-phenylbenzimidazole (II), 5(6)-nitro-2-(4-nitrophenyl)benzimidazole (III), 5(6)-nitro-2-(3-nitrophenyl)benzimidazole (IV), and 2-(4-nitrophenyl) benzimidazole (V), obtained by electrochemical reduction in dimethylformamide (DMF) in a Bu₄NClO₄ -base electrolyte in the presence of Bu₄NOH (VI), were studied. Under the influence of VI, these compounds split out a proton from the imidazole ring and give anions I–V, which are capable of adding an electron reversibly. It was shown that the unpaired electron in I and II is localized in the benzimidazole system and that the splitting of the nitrogen atom of the nitro group does not depend significantly on the substituent in the phenyl ring. The introduction of a nitro group in the phenyl ring (III–V) leads to localization of the unpaired electron on it. The nature of the substituent in the benzimidazole system has a significant effect on the splitting constant for the nitrogen atom of the nitro group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 530–531, April, 1979.We thank T. A. Maslennikova for kindly providing us with the compounds for the investigation.     

Synthesis and properties of 5-chloro-4-nitropyrazoles

The nitration of 5-chloropyrazoles with a mixture of 100% nitric acid and 65% oleum or a mixture of 60% nitric acid and polyphosphoric acid gave substituted 5-chloro-4-nitropyrazoles in 45–91% yield. The nitration of 3-aryl-5-halopyrazoles was accompanied by introduction of a nitro group into the aromatic ring. 4-Chloropyrazoles failed to undergo nitration under these conditions. The reaction of 5-chloro-1,3-dimethyl-4-nitropyrazole with ethyl cyanoacetate in DMSO in the presence of K₂CO₃ led to the formation of ethyl 2-cyano-2-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)acetate.     

Preparation, crystal structure, and spectroscopic, chemical, and electrochemical properties of (2E,4E)-4-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1,3-butadiene compared with those of (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene

Wittig reaction of 3-[4-(dimethylamino)phenyl]propanal (5) with (3-guaiazulenylmethyl)triphenylphosphonium bromide (4) in ethanol containing NaOEt at 25 °C for 24 h under argon gives the title (2E,4E)-1,3-butadiene derivative 6E in 19% isolated yield. Spectroscopic properties, crystal structure, and electrochemical behavior of the obtained new extended π-electron system 6E, compared with those of the previously reported (E)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)ethylene (12), are documented. Furthermore, reaction of 6E with 1,1,2,2-tetracyanoethylene (TCNE) in benzene at 25 °C for 24 h under argon affords a new Diels-Alder adduct 8 in 59% isolated yield. Along with spectroscopic properties of the [π4+π2] cycloaddition product 8, the crystal structure, possessing a cis-3,6-substituted 1,1,2,2-tetracyano-4-cyclohexene unit, is shown. Moreover, reaction of 6E with (E)-1,2-dicyanoethylene (DCNE) under the same reaction conditions as the above gives no product; however, this reaction in p-xylene at reflux temperature (138 °C) for four days under argon affords a new Diels-Alder adduct 9 in 54% isolated yield. Although reaction of 6E with DCNE in toluene at reflux temperature (110 °C) for four days under argon provides 9 very slightly, reaction of 6E with dimethyl acetylenedicarboxylate (DMAD) in toluene at reflux temperature for two days under argon yields a new Diels-Alder adduct 10, in 58% isolated yield, which upon oxidation with MnO₂ in CH₂Cl₂ at 25 °C for 1 h gives 11, converting a (CH₃)₂N-4″ into CH₃NH-4″ group, in 37% isolated yield. The crystal structure of 11 supports the molecular structure 10 possessing a partial structure cis-3,6-substituted 1,2-dimethoxycarbonyl-1,4-cyclohexadiene. The title basic studies on the above are reported in detail.     

γ-Lactonizations of 2H-chromenes via cyclopropanation

A two-step synthesis of tetrahydro-2H-furochromenones from 2H-chromenes is reported. The reaction of a series of tert-butyl 2-diazoacetate derivatives with 2H-chromenes, catalyzed by Rh₂(OAc)₄, generated cyclopropane intermediates that rearranged to γ-lactones on treatment with Sn(OTf)₂.