Reactions of <Emphasis Type="Italic">N</Emphasis>-and <Emphasis Type="Italic">C</Emphasis>-Alkenylanilines: VII. Synthesis of Indole Heterocycles from Products of Reaction between <Emphasis Type="Italic">N</Emphasis>-Mesyl-2-(1-alken-1-yl)anilines and Halogens

N-Mesyl-2-(1-methyl-1-butenyl)-6-methylaniline reacted with Br₂ to afford N-mesyl-2-(3-bromo-1-penten-2-yl)aniline that under treatment with NH₃ or amines underwent cyclization into N-mesyl-7-methyl-3-methylene-2-ethylindoline. The reaction of N-mesyl-2-(1-methyl-1-buten-1-yl)-4-methyl- and 2-(1-methyl-1-buten-1-yl)aniline with Br₂ gave rise to the corresponding N-mesyl-2-(2-bromo-1-methyl-1-buten-1-yl)anilines. Under the similar conditions N-tosyl-2-(1-cyclohexen-1-yl)aniline was converted into N-tosyl-2-(6-bromo-1-cyclohexen-1-yl)aniline that under treatment with NH₃ furnished N-tosyl-1,2,3,9a-tetrahydrocarbazole. The reaction of N-mesyl-1,2,3,9a-tetrahydrocarbazole with CuBr₂ in MeOH afforded N-mesyl-4-methoxy-1,2,3,4-tetrahydrocarbazole. N-Mesyl-6-methyl-2-(1-cyclopenten-1-yl)aniline in reaction with Br₂ in the presence of NaHCO₃ was oxidized into the corresponding cyclopentenone, and with NBS it gave N-mesyl-2-(2-bromo-1-cyclopenten-1-yl)aniline.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 730–737.Original Russian Text Copyright © 2005 by Gataullin, Sotnikov, Spirikhin, Abdrakhmanov.     

DFT theoretical studies of anions of aniline and its several derivatives

Detailed studies of the molecular and electronic structures, vibrational frequencies, and infrared intensities of [M ⁻] and [M-H ⁻] anions of aniline and its derivatives (2-, 3-, 4-fluoroanilines, N-[(2E)-1-methylbut-2-en-1-yl]aniline, (2-cyclopent-2-en-1-ylphenyl)amine, N-[(2E)-1-methylbut-2-en-1-yl]aniline, and N-cyclopent-2-en-1-ylaniline) have been carried out using the density functional method with UB3LYP functional and 6-31G** basis set augmented with sp diffuse functions on nitrogen, fluorine, and three carbon atoms of benzene ring (in 2, 4, and 6 positions). For comparison, similar calculations were carried out for the closed-shell neutral molecules ([M]). The studies have provided detailed insight into the structure changes that take place in negative ions of aniline and its derivatives.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Reaction between isoprene and aniline on complex palladium catalysts

Isoprene and aniline have been reacted on the catalytic system Pd(acac)₂-Ph₃P to form a mixture of isomeric telomers: N-(dimethyloctadien-2,7-yl-1)anilines and N-(dimethyloctadien-1,7-yl-3)anilines but on the catalytic system Pd(acac)₂-Ph₃P-CF₃COOH the main product is a mixture of N-(methylbuten-2-yl)aniline adducts. The reaction between N-methylaniline and isoprene on the latter catalyst also gives a mixture of N-methyl and N-(methylbuten-2-yl)aniline adducts.A. N. Nesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1794–1798, August, 1992.     

Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes catalyzed by manganese compounds and complexes

Manganese compounds and complexes [MnCl₂, MnBr₂, Mn(OAc)₂, Mn(acac)₂, Mn(acac)₃, Mn₂(CO)₁₀] catalyze Ritter reaction of organic nitriles with 1-bromo- and 1-hydroxyadamantanes. The reaction proceeds in water environment in the absence of acids at 100–130°C over 3–5 h and affords N-(adamantan-1-yl)amides in 75–100% yields.     

Vanilline Alkanoates in the Synthesis of Hexahydrobenzacridine and Octahydroxanthene Derivatives

Cascade heterocyclization of 1,3-cyclohexanedione and dimedone with 2-naphthylamine and vanilline esters gave derivatives of 2-methoxy-4-(alkyl-11-oxo-7,8,9,10,11,12-hexahydrobenz[a]acridin-12-yl)- and 2-methoxy-4-(alkyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl esters of aliphatic (C₁– C₄ ) carboxylic acids.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 4, 2005, pp. 654–658.Original Russian Text Copyright © 2005 by Kozlov, Basalaeva.     

Reaction of <Emphasis Type="Italic">N</Emphasis>-Sulfinyltrifluoromethanesulfonamide CF<Subscript>3</Subscript>SO<Subscript>2</Subscript>N=S=O with Carbonyl Compounds

N-Sulfinyltrifluoromethanesulfonamide CF₃SO₂N=S=O reacts with salicylaldehyde, 2-furaldehyde, 2-thiophenecarbaldehyde, 3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, and 2-phenyl-2H-1,2,3-triazole-4-carbaldehyde to afford the corresponding N-aryl(hetaryl)methylidenetrifluoromethanesulfonamides in high yields. Reactions of the latter with aniline give no adducts at the C=N bond but transamination products. The reaction of trifluoromethanesulfonamide with phenyl isocyanate led to formation of N,N′-diphenylurea instead of expected N-phenyl-N′-(trifluoromethylsulfonyl)urea.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1006–1010.Original Russian Text Copyright © 2005 by Shainyan, Tolstikova.     

Reaction of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)anilines with bromine in the presence of potassium thiocyanate and in methanol

The reactions of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)-6-methylaniline with molecular bromine in the presence of potassium thiocyanate gave N-methylsulfonyl-and N-(ptolylsulfonyl)-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylanilines. N-Methylsulfonyl-2-(cyclopent-1-en-1-yl)-6-methylaniline reacted with bromine in methanol in the presence of NaHCO₃ or with CuBr₂ in MeOH to afford N-methylsulfonyl-2-(5-methoxycyclopent-1-en-1-yl)-6-methylaniline. The reaction of N-methylsulfonyl-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylaniline with diethylamine led to the formation of N-methylsulfonyl-2-{5-[diethylamino(thioxo)methyl]aminocyclopent-1-en-1-yl}-6-methylaniline which was converted into 5-methyl-4-methylsulfonyl-2,3,3a,4-tetrahydrocyclopenta[b]indole by heating with potassium hydroxide.     

Cyclization of ortho-(alk-2-enyl)anilines under the action of iodine

The reaction of ortho-(cyclohex-2-enyl)aniline with I₂ in nonpolar and polar solvents affords predominantly 1-iodohexahydrocarbazole and azatricyclotridecatriene, respectively. Under analogous conditions, 4-methyl-2-(1-methylbut-2-en-1-yl)aniline undergoes cyclization to form exclusively products with quinoline structures regardless of the solvent used.     

Kinetics,catalysis, and mechanism of isomerization of N-[(benzotriazol-1-yl)methyl]anilines into the benzotriazol-2-yl derivatives

The ¹H NMR technique was applied for the measurement of the isomerization rates of N-ethyl-N-[(benzotriazol-1-yl)methyl]aniline ( 4 ) and 4-butyl-N-[(benzotriazol-1-yl)methyl]aniline ( 7 ) to the corresponding benzotriazol-2-yl isomers in dioxane-d₈ at 35°C. The rate constants obtained for pure dioxane-d₈ were 1.62 and 0.28 h^?1 for 4 and 7 , respectively. For both compounds, addition to acetic acid to the dioxane solutions accelerated the isomerizations whereas addition of triethylamine retarded it strongly. Addition of water slowed the isomerization of 4 but accelerated that of 7 : the different effects operating in the two cases are discussed and rationalized. © 1995 John Wiley & Sons, Inc.     

Concise Synthesis of 1,3-Diacetoxy-2-[2′-(2′′,4′′-difluorophenyl)prop-2′-en-1′-yl]propane: An Intermediate for Posaconazole

A concise process of 1,3-diacetoxy-2-[2′-(2″,4″-difluorophenyl)prop-2′-en-1′-yl]propane has been developed. Diethyl malonate was C-alkylated with 2,3-dichloropropene and then the ester groups were reduced by LiAlH₄, followed by acylation to provide 2-(2′-chloroprop-2′-en-1′-yl)-1,3-diacetoxypropane. The chloropropene was finally coupled with 2,4-difluorophenylmagnesium bromide and catalyzed by Fe(acac)₃ to afford the title compound in good total yield.     

Synthesis of N-acetyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles from N- and 2-(cyclopent-2-en-1-yl)anilines

Reactions of 2-bromo-N-(cyclopent-2-en-1-yl)-4-methylaniline and N-(cyclopent-2-en-1-yl)-2-iodo-4,6-dimethylaniline with acetyl bromide in the presence of potassium carbonate gave mixtures of syn and anti atropisomers of the corresponding N-acetyl derivatives at ratios of 1: 1 and 3: 2 respectively. Heating of these mixtures in toluene in the presence of Pd(OAc)₂, PPh₃, Et₃N, and K₂CO₃ (KOAc) afforded mixtures of isomeric N-acetyl-7-methyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 3: 1 or N-acetyl-5,7-dimethyl-3,3a,4,8b- and -1,3a,4,8b-tetrahydrocyclopenta[b]indoles at a ratio of 2: 3. N-Acetyl-3,3a,4,8b-tetrahydrocyclopenta[b]indole was found to undergo thermal isomerization into N-acetyl-1,3a,4,8btetrahydrocyclopenta[b]indole.     

Heterogenization of palladium(II) chelates on a sibunite

Summary Heterogenized palladium(II) chelates have been prepared by a sibunite treatment of acetone or aqueous solutions of palladium complexes with alizarin red C, 4- anilino-pent-3-en-2-one,N, N-bis(acetylacetone)ethylenediamine, 1-phenyl-4-methylpent-4-en-1,3-dione and 1-phenyl-3-anilino-4-methylpent-4-en-1-one. The catalytic properties of these chelates in chloronitrobenzene hydrogenation have been studied. It was found that the catalytic activity approaches 159 mol H₂ (mol Pd min)^–1 depending on the chlorine atom position in the aromatic ring and the nature of the solvent. The catalysts do not lose their activity after five cycles. The products of chloronitrobenzene hydrogenation are chloroanilines (up to 90%), azo- and azoxychlorobenzenes (5–7%) as a result of incomplete reduction as well as small quantities (2–5%) of dehalogenated azo-, azoxybenzenes and aniline.     

Amidines: synthesis from o-alkenylanilines and cyclization in polyphosphoric acid

Condensation of 2-[(E)-pent-3-en-2-yl]-4-, 2-[(E)-pent-2-en-2-yl]-4-, or 2-(cyclopent-1-enyl)-6-methylaniline with 1-chloro-1-(N-methylimino)- or 1-chloro-1-(N-phenylimino)ethane affords the corresponding amidines. Cyclization of the N-methylimino derivatives in polyphosphoric acid gives 3,4-dihydroquinazolines in high yields.     

Synthesis of new carbamate derivatives of indole and their modification

Oximation of indoles having a methoxycarbonylamino group on C⁵ and an acyl group on C³ with hydroxylamine hydrochloride in the presence of pyridine gave the corresponding oximes. The reduction of the 3-C=O group with sodium tetrahydridoborate in the presence of sodium hydroxide was accompanied by removal of the methoxycarbonyl group at the pyrrole nitrogen atom with formation of racemic alcohols. 1,4-Addition of 1-(pyridin-3-yl)butane-1,3-dione to dimethyl 1,4-benzoquinone diimine N,N′-dicarboxylate in dioxane in the presence of sodium methoxide, followed by heating in boiling 22% hydrochloric acid, afforded methyl 2-methyl-5-(methoxycarbonylamino)-3-(pyridin-3-ylcarbonyl)-1H-indole-1-carboxylate. 3-(Dimethylamino)-1-(4-methyl-1,2,5-oxadiazol-3-yl)prop-2-en-1-one reacted with N,N′-bis(methoxycarbonyl)- and N,N′-bis(phenylsulfonyl)-1,4-benzoquinone diimines in methylene chloride and acetic acid, respectively, in the presence of BF₃ · Et₂O to produce indoles having a 1,2,5-oxadiazolylcarbonyl group on C₃.     

Arylbiguanides in Heterocyclization Reactions

The reactions of arylbiguanides with acetyacetone derivatives were used to obtain N-(pyrimidin-2-yl)-N′-arylguanidines, and the reactions with acetoacetic ester derivatives (depending on the structure of the keto esters), N-aryl-N′-(4-oxo-3,4-dihydropyrimidin-2-yl)guanidines or 2-amino-4-arylamino-6-aryl(heteryl)-sulfanylmethylene-1,3,5-triazines. The N-aryl-N′-heterylguanidines formed by the reactions with anhydrides, acyl halides, and aryl isocyanates give rise to the corresponding triaza derivatives.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 2, 2005, pp. 331–339.Original Russian Text Copyright © 2005 by Kryl’skii, Shikhaliev, Shestakov, Liberman.     

Synthesis of indolines and tetrahydroquinolines fromortho-(alk-2-enyl)anilines

Intramolecular cyclization ofo-alkenylanilines was studied. Heating ofo-(cyclopent-2-en-1-yl) arylammonium chlorides at 200–220 °C yields cyclopenta[b]indolines as the main reaction products. Cyclization of 4-methyl-2-(pent-3-en-2-yl)aniline under the same conditions gave a mixture of indolines and tetrahydroquinolines. An alk-1-enylarylamine containing a vinylic double bond does not form cyclization products on the nitrogen atom. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 975–978, May, 1999.     

Synthesis of Drim-9(11)-en-8α- and -8β-ols from Drimenol

Drim-9(11)-en-8α-ol and drim-9(11)-en-8β-ol were synthesized in six steps from drimenol. Drimenol was oxidized by P₂O₅ and DMSO to drimenal, which isomerized with p-TsOH into isodrimenal. Isodrimenal was reduced by NaBH₄ into isodrimenol, epoxidation of which by m-CPBA gave a mixture (3.4:1) of α- and β-epoxyisodrimenols. These reacted with tosyl chloride in Py to give a mixture of α- and β-epoxyisodrimenol tosylates. Treatment of the tosylate mixture with KI and then Ph₃P produced a mixture of drim-9(11)-en-8α- and -8β-ols that was separated chromatographically. The overall yield was ∼26%.__________Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 152–155, March–April, 2005.     

Synthesis of 3-(6-R-Benzothiazol-2-yl)-4-methyl-1,2,5-oxadiazoles

The nitrosation of N-aryl-3-oxobutanethioamides afforded 1-(6-R-benzothiasol-2-yl)-1-hydroxyimino-2-propanones that at oximation with hydroxylamine were converted into 1-(6-R-benzothiazol-2-yl)-1,2-dihydroxyiminopropanes. The latter were dehydrated by heating with succinic anhydride at 140°C yielding therewith 3-(6-R-benzothiazol-2-yl)-4-methyl-1,2,5-oxadiazoles.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 759–761.Original Russian Text Copyright © 2005 by Britsun, Borisevich, Samoilenko, Lozinskii.     

New unsymmetrical μ-phenoxo bridged binuclear copper(II) complexes

A series of binuclear Cu^II complexes [Cu₂XL] ⁿ⁺ having two copper(II) ions bridged by different motifs (X = OH^–, MeCO₂ ^–, or Cl^–) have been prepared using the ligands: H₂L¹ = 4-methyl-2-[N-(2-{dimethylamino}ethyl-N-methyl)aminomethyl]-6-[(prolin-1-yl)methyl]phenol, H₂L² = 4-nitro-2-[N-(2-{dimethylamino}ethyl-N-methyl)aminomethyl]-6-[(prolin-1-yl)methyl]phenol, H₂L³ = 4-methyl-2-[N-(2-{diethylamino}ethyl-N-ethyl)aminomethyl]-6-[(prolin-1-yl)methyl]phenol and H₂L⁴ = 4-nitro-2-[N-(2-{diethylamino}ethyl-N-ethyl)aminomethyl]-6-[(prolin-1-yl)methyl]phenol. The complexes have been characterized by spectroscopic, analytical, magnetic and electrochemical measurements. Cryomagnetic investigations (80–300 K) revealed anti-ferromagnetic exchange between the Cu^II ions (–2J in the range –50 to –182 cm^–1). The strength of anti-ferromagnetic coupling lies in the order: OAc > OH > Cl. Cyclic voltammetry revealed the presence of two redox couples, assigned to Cu^II/Cu^II/Cu^II/Cu^I/Cu^I/Cu^I. The first reduction potential is sensitive to electronic effects from the aromatic ring substituents and steric effect on the donor nitrogens (side arm) of the ligand systems.