Showing papers in "Russian Journal of Organic Chemistry in 2013"

Morpholines. Synthesis and biological activity

Abstract: The review analyzes methods of synthesis of 1,4-oxazines (morpholines) starting from vicinal amino alcohols and their derivatives, oxiranes, and aziridines. Examples of using morpholines in medicinal and organic chemistry as catalysts, auxiliaries, biologically active substances, and building blocks for their preparation are considered. The data published until February 2013 have been covered.

New syntheses of [1,2,5]oxadiazolo[3,4- e ][1,2,3,4]tetrazine 4,6-dioxide

Abstract: New methods were developed for the synthesis of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide from 4-(tert-butyl-NNO-azoxy)-N-nitro-1,2,5-oxadiazol-3-amine or its alkali metal salts and acid anhydrides (or chlorides) in the presence of strong acids. The yield of [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide in acetic anhydride in the presence of sulfuric acid or sulfuric anhydride at 20°C in 20 min attained 83%. A general mechanism was proposed for the reactions under study. Acetyl group behaved for the first time as departing group in the synthesis 1,2,3,4-tetrazine 1,3-dioxides, and [1,2,5]oxadiazolo[3,4-e][1,2,3,4]tetrazine 4,6-dioxide was obtained in 47% yield from N-[4-(acetyl-NNO-azoxy)-1,2,5-oxadiazol-3-yl]acetamide.

Synthesis, Properties, and Structure of Tetrazoles: Certain Achievements and Prospects

Abstract: The review generalizes and systematizes the results of research on the synthesis and properties of tetrazole derivatives obtained in the Belarusian State University within the last decade. The main attention is fixed on important directions in the tetrazole synthesis: the acid-catalyzed N-alkylation, the reactions of primary amines with triethyl orthoformate and sodium azide followed by the heterocyclization of imidoyl azides, and on the transformation of the obtained 1-aryltetrazoles into 1-aryl-5-aminotetrazoles. The results of quantum-chemical and X-ray investigations as well as aspects of the practical application of tetrazoles are reviewed.

Synthesis of 1,5-disubstituted (E)-pent-2-en-4-yn-1-ones

Abstract: The condensation of 3-arylpropynals with aryl methyl ketones in the presence of sodium hydroxide in 50% aqueous ethanol at 0°C (Claisen-Schmidt reaction) afforded up to 89% of the corresponding (E)-1,5-diarylpent-2-en-4-yn-1-ones. The E configuration of the double C=C bond and cis conformation of the enone fragment in the products in crystal and CDCl3 solution were determined by X-ray analysis and 1H NMR spectroscopy.

Synthesis and luminescence properties of 2-(2-benzoyloxyphenyl)-5-aryl-1,3,4-oxadiazoles

Abstract: Bidentate ligand systems based on 2-hydroxyphenyloxadiazole attract strong interest due to application of metal complexes derived therefrom in photoand electroluminescent devices as blue-emitting chromophores, as well as electron-transporting materials that improve charge transfer balance in organic light-emitting diodes (OLEDs) [1, 2]. In addition, organic luminophores based on diphenyloxadiazoles exhibit an anomalously high Stokes shift (ASS), which favors increase in the light yield as a result of reduced self-absorption and minimizes liminophore photodegradation [3].

Synthesis of substituted tryptanthrins via oxidation of isatin and its derivatives

Abstract: Oxidation of isatin and its 5-substituted analogs with potassium permanganate in anhydrous acetonitrile gave indolo[2,1-b]quinazoline-6,12-dione (tryptanthrin) and its 2,8-dimethyl-, 2,8-dibromo-, and 2,8-diiodo derivatives. Oxidative coupling of 5,7-dichloroisatin with isatin under analogous conditions afforded 2,4-dichloroindolo[2,1-b]quinazoline-6,12-dione, while 1,4-dichloroindolo[2,1-b]quinazoline-6,12-dione and 1,4-dichloro-8-methylindolo[2,1-b]quinazoline-6,12-dione were obtained by oxidative coupling of 4,7-dichloroisatin with isatin and 5-methylisatin, respectively.

Theoretical evaluation of conformational preference of ethane molecule encapsulated in a nanotube

Abstract: It is known that nanotubes considerably affect the physicochemical characteristics of encapsulated molecules and may essentially change the properties of the latter [1]. In this study using semiempirical approximations АМ1 and TNDO in the framework of HyperChem software [2] and DFT-method PBE/3z (PRIRODA program package [3]) the conformational behavior was investigated of an ethane molecule placed into a single-wall model nanotube С104Н8 (l 16 A, O 5.6 A) with the distance of the hydrogen atoms of the ethane molecule to the nanotube walls equal 1.8–1.9 A. The proper ethane molecule is known to be characterized by the hindered rotation; the potential barrier to the transition between the staggered conformations equals 2.8–3.04 kcal mol–1 as measured by heat capacity and spectroscopy studies [4–6]. The preference of the staggered form may be explained by the mutual repulsion of the valence nonbonded atoms [4] or the contiguous С–Н bonds [5] or from the stabilizing effect of electronic interactions [6]. The calculation results show that the relative stability of the staggered conformer of ethane (∆Н≠, ∆G≠) depending on the used approximation eqials from 1.3 to 3.3 kcal mol–1 (see the table). Therewith the length of the carbon–carbon bond in this form is slightly shorter than in the eclipsed conformation, and the order of the С–С bond in both conformers (PBE/3z data) is practically equal and close to unity. The ethane molecule encapsulated in the nanotube contrary to expectations was the most stable in the eclipsed conformation (АМ1, TNDO), or both forms turned out to be degenerate in the energy (PBE/3z). Therewith the difference in the length of the С–С bond Energy and structural parameters of ethane molecule

Synthesis of functionally substituted isoxazole and isothiazole derivatives

Abstract: Acylation of benzene and toluene with 5-phenyl- and 5-(p-tolyl)isoxazole-3-carbonyl chlorides gave 5-phenyl(or p-tolyl)isoxazol-3-yl phenyl(or p-tolyl)ketones which were reduced to the corresponding alcohols with sodium tetrahydridoborate in propan-2-ol Selective reduction of the carboxy group in 4,5-dichloroisothiazole-3-carboxylic acid was achieved by the action of BH3, and the aldehyde group in 4-formyl-2-methoxyphenyl 5-arylisoxazole-3-carboxylates and 4,5-dichloroisothiazole-3-carboxylates was reduced to hydroxymethyl group with sodium triacetoxyhydridoborate in benzene Acylation of the resulting hydroxymethyl derivatives with 5-arylisoxazole- and 4,5-dichloroisothiazole-3-carbonyl chlorides afforded the corresponding esters containing two azole fragments in their molecules

Enantioselective synthesis of γ-aminobutyric acid derivatives by Ni(II)-catalyzed reaction of diethyl malonate with nitroalkenes

Abstract: A new synthetic approach to (3R)-4-amino-3-methylbutyric acid and [(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide [(R)-phenotropil] has been developed. Asymmetric center with a required configuration has been generated via enantioselective addition of diethyl malonate to 1-nitropropene and β-nitrostyrene, catalyzed by Ni(II) complexes with (R,R)- and (S,S)-N,N′-dibenzylcyclohexane-1,2-diamine.

Chemistry of iminofuran: VIII. Recyclization of 5-aryl-3-arylimino-3H-furan-2-ones effected by cyanoacetic acid derivatives

Abstract: The recyclization of 5-aryl-3-arylimino-3H-furan-2-ones under the action of esters, nitriles, and amides of cycnoacetic acids resulted in the corresponding esters, nitriles, and amides of (5E)-2-amino-1-aryl-4-oxo-5-(2-oxoethylidene)-1H-4,5-dihydropyrrole-3-carboxylic acids.

Five-membered 2,3-dioxo heterocycles: XCVIII. [4 + 2]-cycloaddition of alkyl vinyl ethers to 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones. A new synthetic approach to heteroanalogs of 13(14→8)-abeo steroids

Abstract: 3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with alkyl vinyl ethers according to the [4 + 2]-cycloaddition pattern with formation of substituted (1S*,16R*)- and (1R*,16R*)-16-alkoxy-14-aryl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-triones. The structure of (1S*,16R*)-7-chloro-16-ethoxy-14-phenyl-3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-trione was determined by X-ray analysis. A new synthetic approach was developed to heteroanalogs of 13(14→8)-abeo steroids, substituted 3,15-dioxa-10-azatetracyclo[8.7.0.01,13.04,9]heptadecanes.

Conformational behavior of ethane molecule encapsulated in a nanotube

Abstract: Investigation of conformation transformations of ethane molecule in single-wall carbon nanotubes by the hybrid DFT method PBE/3z showed that the parameters and the character of the nanotube (length, diameter, open, closed, or semiopened) affect the conformational behavior of the encapsulated molecule leveling the difference in the energy or even resulting in the inversion of the relative stability of the staggered and eclipsed forms.

Improved synthesis of tertiary propargyl alcohols by the Favorskii reaction of alkyl aryl (hetaryl) ketones with acetylene

Abstract: Alkyl aryl (hetaryl) ketones react with acetylene under atmospheric pressure in the superbasic system KOH-EtOH-H2O-DMSO at 10–15°C (2 h) to give the corresponding tertiary propargyl alcohols in up to 91% yield. The procedure requires no large excess of KOH and low-boiling inflammable solvents, produces few wastes, and is safe and convenient on the laboratory scale; there are no limitations for its large-scale application.

Steric effect of substituents in haloarenes on the rate of cross-coupling reactions

Abstract: The relative reactivity of ortho- and para-methyl-substituted iodoarenes in the Sonogashira reaction and palladium-catalyzed methoxycarbonylation, as well as of similarly substituted bromoarenes in the Suzuki reactions and cobalt-catalyzed methoxycarbonylation, was studied. Introduction of a methyl group into the para position of aryl halide slows down the cross-coupling. o-Methylhaloarenes are less reactive in palladiumcatalyzed reactions as compared to both unsubstituted haloarene and para-substituted analog. The presence of a methyl group in the ortho position with respect to the reaction center accelerates cobalt-catalyzed methoxycarbonylation.

Synthesis of secondary propargyl alcohols from aromatic and heteroaromatic aldehydes and acetylene in the system KOH-H2O-DMSO

Abstract: Ethynylation of aromatic and heteroaromatic aldehydes with acetylene under atmospheric pressure in the catalytic system KOH-H2O-DMSO (aldehyde-KOH molar ratio 1 : 2, −5 to −7°C, 3 h) gave secondary propargyl alcohols in 46–67% yield.

Advances in the synthesis of cycloalka[b]indoles

Abstract: The review considers new advances in the synthesis of indoles annulated with cycloalkanes.

Regioselective reaction of tellurium tetrabromide with 1-hexene and methanol

Abstract: Published information on the reactions of tellurium tetrabromide with alkenes [1] and alkynes [2] is scanty. The known feature of tellurium tetrabromide is its low solubility in most organic solvents resulting often in incomplete conversion of this reagent. The purifi cation of reaction products from tellurium tetrabromide is a complicated problem. Tellurium tetrabromide is well soluble in methanol but this solvent has not been virtually used in the reactions of tellurium tetrabromide apparently because of the apprehension of the alcoholysis of the Te–Br bond. No published information exists on the reactions of tellurium tetrabromide with 1-hexene. In continuation of research on the reactions of tellurium [3] and selenium [4] halides with unsaturated compounds we performed the reaction between tellurium tetrabromide with 1-hexene in methanol. The reaction proceeds chemoand regioselectively with the selective formation in a quantitative yield of the product of TeBr4 addition to the hexane molecule in keeping with Markovnikoff rule, 2-methoxyhexyltellurium tribromide (I). The quantitative yield of compound I was obtained by heating the reagents at 40–60°С during 8 h. We did not observe bisadduct formation and the possible alcoholysis of the Te–Br bond.

Synthesis and properties of N-(allyl)trifluoromethanesulfonamide

Abstract: We have recently synthesized the first N-alkenylsubstituted trifluoromethanesulfonamide, N-methyl-N[(E)-2-phenylethenyl]trifluoromethanesulfonamide CF3SO2N(Me)CH=CHPh, by dehydrobromination of N-(2-bromo-2-phenylethyl)-N-(methyl)trifluoromethanesulfonamide [1]. An attempt to obtain in a similar way its NH analog, CF3SO2NHCH=CHPh was unsuccessful; instead of the dehydrobromination product, we isolated 2,5-diphenyl-1,4-(trifluoromethylsulfonyl)piperazine [2]. However, N-monosubstituted trifluoromethanesulfonamides CF3SO2NHR attract particular interest as strong NH acids which can be functionalized at the nitrogen atom. Therefore, the present communication describes the synthesis and transformations of the first unsaturated NH trifluoromethanesulfonamide, N-(allyl)trifluoromethanesulfonamide (I).

Fe-catalyzed synthesis of (4E)-tridec-4-en-1-yl acetate, sex pheromone of tomato pinworm (Keiferia lycopersicella)

Abstract: Starting with industrially available 1,3-dichloropropene a stereoselective process was developed for the preparation of (4E)-tridec-4-en-1-yl acetate, sex pheromone of tomato pinworm (Keiferia lycopersicella) using in the key stage the Fe-catalyzed cross-coupling of ethyl (4E)-5-chloropent-4-enoate with octylmagnesium bromide.

Alkylation of 1,1-bis(methoxy-NNO-azoxy)alkanes under phase-transfer catalysis

Abstract: 1,1-Bis(methoxy-NNO-azoxy)alkanes were alkylated in high yield at the central carbon atom under conditions of phase-transfer catalysis with selective formation of mono- and dialkyl derivatives.

Synthesis of thietanyl-substituted pyrimidine-2,4(1H,3H)-dions

Abstract: Reactions of 6-methylpyrimidine-2,4(1H,3H)-dione or 5-hydroxy-6-methyl-pyrimidine-2,4(1H,3H)-dione with 2-chloromethylthiirane afforded the corresponding substituted 1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-diones The calculations in the framework of approximations PBE/3z, B3LYP/6-31G++(d,p) and MP2/6-31G++(d,p) showed that the alkylation occurred at the atom N1 of the pyrimidine ring

Spiro heterocyclization of 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitriles to 3H-pyrrole derivatives, 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

Abstract: 4-Aryl-3-methyl-4-oxobutane-1,1,2,2-tetracarbonitriles reacted with morpholine to give 8-amino-3aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles. Ar = Ph (a), 4-ClC6H4 (b), 4-MeC6H4 (c). 4-Oxoalkane-1,1,2,2-tetracarbonitriles are extensively studied representatives of the series of polynitrile compounds. Derivatives of 4-oxoalkane-1,1,2,2tetracarbonitriles are known as potential antitumor agents [1] and coordination polymers with interesting topology [2]. We now perform extensive studies on the transformations of 4-oxoalkane-1,1,2,2-tetracarbonitriles by the action of nitrogen-centered nucleophiles [3]. 4-Oxoalkane-1,1,2,2-tetracarbonitriles were reported to react with ammonia and amines to form 3-amino-7oxo-4,6-diazabicyclo[3.2.1]oct-2-ene-1,2-dicarbonitriles [4], 3-amidinio-2-aminopyridine-4-carboxylates [5], diethylammonium 3,4-dicyano-5,6,7,8-tetrahydroquinolin-2-olates [6], and ammonium 4-aryl-4oxo-1,1,2-tricyanobut-2-en-1-ides [7]. We recently showed that the reaction of 4-oxoalkane-1,1,2,2-tetracarbonitriles with morpholine leads to 5-amino-2(morpholin-4-yl)-3H-pyrrole-3,4-dicarbonitriles [8, 9] and found that nitrogen-centered nucleophiles preferably add to the β-cyano groups of polyelectrophilic tetranitriles. The resulting compounds are representatives of a poorly explored class of aza heterocycles, 3H-pyrroles, which may be regarded as nitrogen-containing cyclopentadiene analogs. Despite limited published data, some 3H-pyrroles were found to exhibit antimicrobial and antitumor activity [10–12]. With a view to synthesize new functionally substituted 3H-pyrrole derivatives, we extended the series of 4-oxoalkane-1,1,2,2-tetracarbonitrile substrates and examined their reaction with morpholine in more detail. The reactions of 4-aryl-3-methyl-4-oxobutane-1,1,2,2DOI: 10.1134/S1070428013060110

Reactivity of 7-amino-3- tert -butyl-4-oxo-4,6-dihydropyrazolo[5,1- c ][1,2,4]triazine-8-carbonitrile

Abstract: By reaction of carbonyl compounds with 7-amino-3-tert-butyl-4-oxo-4,6-dihydropyrazolo[5,1-c]-[1,2,4]triazine-8-carbonitrile 3-tert-butyl-8-R-4,6,9,10-tetrahydropyrimido[4′,5′:3,4]pyrazolo[5,1-c][1,2,4]-triazine-4,10-diones and (3-tert-butyl-4-oxo-8-cyano-4,6-dihydropyrazolo[5,1-c][1,2,4]triazin-7-yl)acetamide were obtained.

Quantum-chemical calculations of NMR chemical shifts of organic molecules: VIII. Solvation effects on 15N NMR chemical shifts of nitrogen-containing heterocycles

Abstract: Effect of solvation on the accuracy of DFT quantum-chemical calculations of 15N NMR chemical shifts of pyrrole, N-methylpyrrole, and pyridine was studied. The use of continuum model is sufficient to obtain consistent theoretical σN values for weakly polar aprotic solvents, whereas solvation effects in strongly polar and protic solvents should be taken into account in the explicit form.

Condensation of acetylacetone with formaldehyde and thiols

Abstract: Acetylacetone reacted with formaldehyde and thiols in aqueous medium or in the presence of 0.1 equiv of sodium hydroxide to give the corresponding 3-[(alkylsulfanyl)methyl]pentane-2,4-diones which exist in solution as mixtures of diketone and enol tautomers. Four-component condensation of acetylacetone with formaldehyde, methanethiol, and sodium sulfide, depending on the reaction time, led to the formation of a mixture of 1,1-bis(methylsulfanylmethyl)propan-2-one with 1,1′-{3-[(methylsulfanyl)methyl]tetrahydro-2H-thiopyran-3,5-diyl}diethanone or with 8-methyl-5-(methylsulfanylmethyl)-3-thiabicyclo[3.3.1]non-7-en-6-one.

N -allenyl- N -benzyltrifl uoromethanesulfonamide

Abstract: First N-allenyl-substitued triflamides CF3SO2N(Bn)CH=C=CH2 were synthesized from N-allyltriflamides by sucessive reactions of bromination, N-alkylation, and dehydrobromination. Isomeric N-propargyltriflamide CF3SO2N(Bn)CH2C≡CH is present in the reaction products as a minor admixture.

Reaction of ethyl acetoacetate with formaldehyde and primary amines

Abstract: The condensation of ethyl acetoacetate with formaldehyde and primary amines in methanol at 65°C (Mannich reaction) gave up to 92% of hexahydropyrimidine derivatives containing ester and acetyl groups. Analogous reaction with aminopyridines stopped at the stage of formation of linear condensation products.

Bromination-dehydrobromination/debromination of N-Methyl-N-(2-phenylethenyl)trifluoromethanesulfonamide

Abstract: We have recently synthesized the first N-alkenylsubstituted trifluoromethanesulfonamide, N-methyl-N[(E)-2-phenylethenyl]trifluoromethanesulfonamide (I) [1]. With a view to obtain new trifluoromethanesulfonamide derivatives, we tried to synthesize adducts of I with various nucleophiles. However, compound I failed to react with methanol, ethanol, or diethylamine even on prolonged heating under reflux, but it readily took up bromine molecule in dioxane, and the resulting dibromo derivative readily underwent dehydrobromination by the action of alcoholic alkali (Scheme 1). 10.9 Hz), and a doublet at δ 6.58 ppm (J = 9.5 Hz) with a lower intensity. The intensity of the signal at 5.15 ppm was equal to the overall intensity of the signals at δ 6.51 and 6.58 ppm; the intensity ratio of the major and minor downfield signals was about 8 : 1. Assuming that the signal at δ 5.15 ppm is a superposition of two doublets corresponding to the downfield signals at δ 6.51 and 6.58 ppm, we can conclude that adduct II is a mixture of two diastereoisomers at a ratio of 8 : 1. These findings are consistent with the presence in the F NMR spectrum of II of two signals at δF –73.95 and –72.46 ppm with the same intensity ratio. Insofar as initial compound I is trans isomer [1], the major product should be stereoisomer IIa in agreement with the generally preferred trans-addition pattern. This is also supported by the results of HF/6-311G** calculations [2], according to which the energy of isomer IIa is lower by 1.3 kcal/mol than that of IIb. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 6, pp. 924–926. © Pleiades Publishing, Ltd., 2013. Original Russian Text © I.V. Ushakova, B.A. Shainyan, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 6, pp. 938–939.

Synthesis and application of chalcones to the preparation of heterocyclic structures

Abstract: Condensation of methyl N-(4-acetylphenyl)carbamate with aromatic aldehydes in basic and acid environment, and also with hetarylaldehydes in the presence of bases afforded chalcones with the carbamate function. Under the conditions of basic catalysis a nucleophilic substitution was observed of a methoxy group in the carbamate moiety of the chalcone for an ethoxy group. The reactions of the obtained chalcones with hydrazine hydrate, isonicotinic acid hydrazide, guanidine and hydroxylamine hydrochlorides, thiourea, and selenium dioxide furnished the corresponding derivatives of pyrazole, oxazole, pyrimidine, and selenadiazole.