Acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine and tautomerism of the reaction products

The acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine with the chlorides and anhydrides of saturated carboxylic and sulfonic acids leads to N-monoacyl derivatives of dithiazine in 85–96% yields. It was established by IR and UV spectroscopy that 2H,6H-2,6-dimethyl-4-acylamino-1,3,5-dithiazines with donor substituents exist primarily in the amino form and that the equilibrium is shifted to favor the imino form for compounds with acceptor substituents to a greater degree in solutions than in the crystalline state.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 622–626, May, 1982.     

Benzotriazole Mediated Synthesis of Some 5-Alkyl-Dihydro-4H-1,3,5-Dithiazines

An efficient synthesis of N-substituted dihydro-4H-1,3,5-dithiazines is described. N,N-Bis(benzotriazolylmethyl)alkylamines 1 smoothly under go cyclisation reaction in the presence of formaldehyde and hydrogen sulfide to give 5-substituted dihydro-4H-1,3,5-dithiazines 2.     

Reactions of 4-amino-1,3,5-dithiazine with ammonia and amines

It is shown that selective replacement of the sulfur atom in the 3 position by a nitrogen atom, which leads to 2,6-dimethyl-4-amino-3H-2,6-dihydro-1,3,5-thiadiazine, occurs when 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine is treated with ammonium hydroxide. Under the same conditions, amines cause profound destruction of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine with the production of thiourea.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 652–655, May, 1982.     

Synthesis of 1,3-dialkyl-5-(hetaryl-1-yl)-1,3-dihydrobenzimidazol-2-ones

Reactions of 5-amino-1,3-dialkyl-1,3-dihydrobenzimidazol-2-ones with 2,5-dimethoxytetrahydrofuran and 2,6-dimethyl-γ-pyranone led to the formation of 1,3-dialkyl-1,3-dihydro-5-(pyrrol-1-andл)benzimidazol-2-ones and 1-(1,3-dialkyl-2-oxo-1,3-dihydrobenzimidazol-5-yl)-2,6-dimethylpyridin-4-ones.     

The reaction of selenium dichloride with divinyl sulfide

A synthesis of novel selenium heterocycles based on the reaction of selenium dichloride with divinyl sulfide has been described. At −50 °C the reaction affords 2,6-dichloro-1,4-thiaselenane in quantitative yield. At room temperature the reaction gives 2,6-dichloro-1,4-thiaselenane and 5-chloro-2-chloromethyl-1,3-thiaselenolane. Upon standing in chloroform solution, 2,6-dichloro-1,4-thiaselenane undergoes spontaneous rearrangement to 5-chloro-2-chloromethyl-1,3-thiaselenolane. Under the action of pyridine, 2,6-dichloro-1,4-thiaselenane is converted to 2-chloromethyl-1,3-thiaselenole in 95% yield.     

Thiomethylation of amino alcohols using formaldehyde and hydrogen sulfide

Three-component condensations of formaldehyde with hydrogen sulfide and hydroxylamine or amino alcohols at a ratio of 3:2:1 give 47–73% of N-hydroxy(or hydroxyalkyl)-1,3,5-dithiazinanes. The reactions of CH₂O with H₂S and hydroxylamine or α-amino alcohols at a ratio of 4:3:1 involve both amino and hydroxy groups, leading to the corresponding dithiazinanes. 4-Aminobutan-1-ol reacts with CH₂O and H₂S under analogous conditions only at the amino group to form 4-(1,3,5-dithiazinan-5-yl)butan-1-ol.     

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.     

Synthesis of a 6-aryloxymethyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one: a muscarinic (M3) antagonist

A synthesis of the racemic 6-aryloxymethyl-5-hydroxy-2,3,4,5-[1H]-2-tetrahydrobenzazepin-4-one , for evaluation as a muscarinic (M(3)) antagonist, is described. 2-[2-tert-Butyldimethylsilyloxymethyl-6-(2,6-dimethoxyphenoxymethyl)phenyl]propan-2-ol was prepared from 2,6-dimethyl-1-bromobenzene and taken through to N-[3-(2,6-dimethoxyphenoxymethyl)-2-(propen-2-yl)phenyl]methyl-N-prop-2-enyl 2-nitrobenzene sulfonamide . However, attempts to cyclise this diene by alkene metathesis were unsuccessful, the open-chain alkene being the only product isolated in yields of up to 70%. In a second approach to the 6-aryloxymethyl-5-hydroxytetrahydrobenzazepin-4-one, methyl (Z)-3-[2-(1-tert-butyldimethylsilyloxymethyl)-6-(1,6-dimethoxyphenoxymethyl)phenyl]but-2-enoate was converted into (Z)-3-[2-hydroxymethyl-6-(2,6-dimethoxyphenoxymethyl)phenyl]but-2-enyl 2-nitrobenzene sulfonamide which was cyclised under Mitsunobu conditions to the corresponding 2,3-dihydro-[1H]-2-benzazepine . The structure of this was confirmed by an X-ray crystal structure of its 2-(4-bromophenylsulfonyl) analogue , and functional group modification including hydroxylation, attachment of the requisite side-chain at C(2) and further oxidation gave the target compound which was assayed for muscarinic (M(3)) activity.     

Solvent extraction and lanthanide complexation studies with new terdentate ligands containing two 1,3,5-triazine moieties

The extracting agent 2,6-bis(4,6-di-pivaloylamino-1,3,5-triazin-2-yl)-pyridine (L(5)) in n-octanol was found, in synergy with 2-bromodecanoic acid, to give D(Am)/D(Eu) separation factors (SFs) between 2.4 and 3.7 when used to extract the metal ions from 0.02-0.12 M HNO(3). Slightly higher SFs (4-6) were obtained in the absence of the synergist when the ligand was used to extract Am(III) and Eu(III) from 0.98 M HNO(3). In order to investigate the possible nature of the extracted species crystal structures of L(5) and the complex formed between Yb(III) with 2,6-bis(4,6-di-amino-1,3,5-triazin-2-yl)-pyridine (L(4)) were also determined. The structure of L(5) shows 3 methanol solvent molecules all of which form 2 or 3 hydrogen bonds with triazine nitrogen atoms, amide nitrogen or oxygen atoms, or pyridine nitrogen atoms. However, L(5) is relatively unstable in metal complexation reactions and loses amide groups to form the parent tetramine L(4). The crystal structure of Yb(L(4))(NO(3))(3) shows ytterbium in a 9-coordinate environment being bonded to three donor atoms of the ligand and three bidentate nitrate ions. The solvent extraction properties of L(4) and L(5) are far inferior to those found for the 2,6-bis-(1,2,4-triazin-3-yl)-pyridines (L(1)) which have SF values of ca. 140 and theoretical calculations have been made to compare the electronic properties of the ligands. The electronic charge distribution in L(4) and L(5) is similar to that found in other terdentate ligands such as terpyridine which have equally poor extraction properties and suggests that the unique properties of L(1) evolve from the presence of two adjacent nitrogen atoms in the triazine rings.     

Cyclothiomethylation of aryl hydrazines with formaldehyde and hydrogen sulfide

Cyclothiomethylation of phenyl hydrazine with CH₂O and H₂S in a ratio of 1: 3: 2 in an acidic medium (HCl) afforded previously unknown 3-phenyl-1,3,4-thiadiazolidine (35% yield) and N-phenyl(perhydro-1,3,5-dithiazin-5-yl)amine (35% yield). The analogous reaction in an alkaline medium (BuONa) produced N-phenyl(perhydro-1,3-thiazetidin-3-yl)amine (22% yield). The reaction of 1,2-diphenyl hydrazine with CH₂O and H₂S in an alkaline medium gave 1,2,4,5-tetraphenylhexahydro-1,2,4,5-tetrazine and previously unknown 3,4-diphenyl-1,3,4-thiadiazolidine and 5,6-diphenyltetrahydro-1,3,5,6-dithiadiazepine in 39 and 22% yields, respectively. Cyclothiomethylation of benzyl hydrazine afforded previously unknown bis[(6-benzyl-4,2,6-thiadiazolidin-2-yl)methyl] sulfide (60% yield) and N-benzyl(perhydro-1,3,5-dithiazin-5-yl)amine (19% yield). The reaction of tosyl hydrazine produced 3-[(p-tolyl)sulfonyl]-1,3,4-thiadiazolidine, N-(perhydro-1,3,5-dithiazin-5-yl)-p-tolylsulfonamide, and 3,7-bis(p-tolylsulfonylamino)-1,5-dithia-3,7-diazacyclooctane in 21, 38, and 41% yields, respectively. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1758–1767, October, 2006.     

Organometallic aluminum compounds derived from 2-(1,3,5-dithiazinan-5-yl)ethanol ligands

The reactions of AlMe(2)Y (Y = Me or Cl) with new ligands 2-(1,3,5-dithiazinan-5-yl)ethanol (1), 2-(1,3,5-dithiazinan-5-yl)-1-methylethanol (2), and 2-(1,3,5-dithiazinan-5-yl)-1-phenylethanol (3) are described. The ligands are coordinated to aluminum atoms by nitrogen and oxygen atoms, with a nitrogen based spiranic structure. Equimolar reactions gave dimeric structures bearing pentacoordinated aluminum atoms O-(AlMeY)-2-(1,3,5-dithiazinan-5-yl)ethanolates (4-7) as well as monometallic compounds with tetracoordinated aluminum atoms O-(AlMeY)-2-(1,3,5-dithiazinan-5-yl)ethanolates (8-9). Reactions with 2 equiv of the aluminum reagents afforded tetracoordinated dialuminum complexes O-(AlMeY)-O-(AlMe(2)Y)-2-(1,3,5-dithiazinan-5-yl)ethanolate (10-18). The structures of the new compounds were determined by NMR ((1)H,(13)C, and (27)Al) and complemented by X-ray diffraction of compounds 4, 10, and 16-18. Relevant intermolecular interactions C-H...S, C-H...Cl, and C-H...pi found in the crystalline network are reported.     

Cyclocondensation reactions of heterocyclic carbonyl compounds.. Synthesis of 2,6-bis(6-azauracil-5-yl)aniline and its use for synthesis of some other polynuclear 1,2,4-triazines

5-(2-Aminophenyl)-6-azauracil 1 was converted to 7-(6-azauracil-5-yl)isatin 3 , semicarbazone 4 of which was recyclized to 2,6-bis(6-azauracil-5-yl)aniline 5 . This one served as a starting compound for preparation of other noncondensed two nuclear heterocycles 7, 9, 10 and condensed 1,2,4-triazines 11 and 12 as well.     

α-三唑基查尔酮与苯肼的加成-关环反应研究

(Z)或(E)-1,3-二芳基-2-(1H-1,2,4-三唑-1-基)-2-丙烯-1-酮与苯肼在醋酸中反应均生成顺式和反式吡唑啉异构体混合物,但是在三乙胺催化下却只生成反式的异构体。制备了三对顺、反式的1-苯基-3,5-二芳基-4-(1H-1,2,4-三唑-1-基)-2-吡唑啉衍生物,其结构为^1HNMR和元素分析证实,初步论证了经α-氮原子的加成-环化反应机理。     

Synthesis and NMR spectral studies of some 2,6-diarylpiperidin-4-one O-benzyloximes

Variously substituted 2,6-diarylpiperidin-4-one O-benzyloximes were synthesized by the direct condensation of the corresponding 2,6-diarylpiperidin-4-ones with O-benzylhydroxylamine hydrochloride. All the synthesized compounds are characterized by IR, Mass and NMR spectral studies. NMR spectral assignments are made unambiguously by their one-dimensional (1H NMR and 13C NMR) and two-dimensional (1H-1H COSY, NOESY, HSQC and HMBC) NMR spectra. All the synthesized compounds are resulted as single isomer, i.e., exclusively E isomer (9-14). The conformational preference of 2,6-diarylpiperidin-4-one oxime ethers with and without alkyl substituents at C-3 and C-5 has also been discussed using the spectral studies. The observed chemical shifts and coupling constants suggest that compounds 8-13 adopt normal chair conformation with equatorial orientation of all the substituents while compound 14 contributes significant boat conformation along with the predominant chair conformation in solution. The effect of oximination on ring carbons, their associated protons, alkyl substituents and ipso carbons are studied. Every proton in the piperidone ring of the oxime ether is observed as distinct signal due to oximination. The order of chemical shift magnitude in compound 8 is H-2a>H-6a>H-5e>H-3e>H-3a>H-5a. For 9-12, the order is H-6a>H-5e>H-2a>H-3a>H-5a, for 13, H-6a>H-2a>H-5e>H-3a>H-5a and for 14, the order is H-2a>H-6a>H-5e>H-3a>H-5a while the 13C chemical shift magnitude for 8-14 due to oximination is C-2>C-6>C-3>C-5.     

Diastereomerically enriched analogues of the water-soluble phosphine PTA. Synthesis of phenyl(1,3,5-triaza-7-phosphatricyclo[3.3.1.1(3,7)]dec-6-yl)methanol (PZA) and the sulfide PZA(S) and X-ray crystal structures of the oxide PZA(O) and [Cp*IrCl(2)(PZA)

A diastereomerically enriched analogue of 1,3,5-triaza-7-phosphaadamantane (PTA) was obtained by the reaction of PTA lithium salt with benzaldehyde to give the water-soluble derivative phenyl(1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]dec-6-yl)methanol (PZA, 1) as a mixture of two diastereoisomers. PZA derivatives phenyl(1,3,5-triaza-7-phospha-tricyclo[3.3.1.13,7]dec-6-yl)methanol sulfide [PZA(S), 2] and oxide [PZA(O), 3] were also synthesized. The latter was isolated in the solid state, and the X-ray crystal structure of a single diastereoisomer was obtained. Compound 1 was used as a k1-P monodentate ligand toward iridium(III) moieties, and the piano-stool complex [Cp*IrCl2(PZA)] (4) was obtained as a mixture of diastereoisomers both in solution and in the solid state.     

Synthesis,molecular structure,and applications of 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate to the synthesis of novel heterocyclic ring systems

2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate (1) has been prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Deprotonated compound 1a containing both the nucleophilic endocyclic nitrogen atoms and electrophilic exocyclic nitrogen was used for the syntheses of 3-substituted 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]oxadiazoles 2-9 and 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]thiadiazole-3-thione (10) by tandem nucleophilic addition-electrophilic amination reaction. The method promises utility in the synthesis of a variety of other heterocycles. On the other hand, the convenient routes to 7,8-dihydroimidazo[1,2-c][1,3,5]thiadiazine-2,4(6H)-dithione (16) and 2,6,7,8-tetrahydroimidazo[1,2-a][1,3,5]triazine-4(3H)-thione derivative (17) are reported starting from compound 1. The structures of the compounds prepared were established by elemental analyses, IR, NMR, and MS spectra, and in some instances X-ray analyses.     

Synthesis and study of heteroaromatic ligands containing a pyrimidine ring

5-Hexyl-3-[2-(1H-pyrazol-1-yl)pyrimidin-4-yl]amino-1(2)H-1,2,4-triazoles and 2-(3,5-dipropyl-4-ethyl-1H-pyrazol-1-yl)-6-methyl-4-(5-methyl-1H-pyrazol-1-yl)-aminopyrimidine were synthesized by the reaction of 4-chloropyrimidines with 3-araino-5-hexyl-1H-1,2,4-triazole and 3-amino-5-methyl-1H-pyrazole. Their IR, UV, and PMR spectra were investigated. New methods for the preparation of the intermediates, viz., 2-hydrazino-4(3H)-pyrimidinones and 2-(1H-pyrazol-1-yl)-4(3H)-pyrimidinones, that make it possible to obtain these compounds in higher yields are described.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1673–1677, December, 1980.     

The reactions of some ketones with hexamethylphosphoric triamide a novel synthesis of 3,5-dialkyl-2,6-diphenylpyridines

Alkylphenones other than acetophenones are found to react with refluxing HMPT over a reaction time of 5–10 hr affording 3,5-dialkyl-2,6-diphenylpyridines in 8–23% yields. The reaction of acetophenones with the same reagent affords only the corresponding 1,3,5-triarylbenzenes. 1-Acetyladamantane similarly affords 1-methyl-2,6-di-(1-adamantyl)-6-dimethylamino-1,4,5,6-tetrahydropyridine, a possible intermediate in the formation of the pyridine products.     

Investigation of the structure of 2h,6h-2,6-dimethyl-4-amino-1,3,5-dithiazine by IR spectroscopy

It was established by IR spectroscopy that 2H,6H-2,6-dimethyl-4-amino-1,3,5-di-thiazine exists in the amino form in carbon tetrachloride at low concentrations.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1050–1053, August, 1981.     

Synthesis and NMR spectral assignments of novel nitrogen and sulfur heterocyclic compounds

Synthesis and NMR spectral studies of multidentate N and S heterocycles, 1,3,5-tris(N-methylbenzimidazolyl)benzene, 1,3,5-tris(benzimidazolyl)benzene,1,3,5-tris(benzothiazolyl) benzene, 2,2'-bipyridine 3,3'-bis(benzothiazolyl)benzene and 1,2,4,5-tetrakis(benzothiazolyl) benzene have been carried out. 2D (1)H-(1)H PFG-COSY as well as (1)H-(13)C single and multiple bond correlated (2D GRASP-HSQC and GRASP-HMBC) experiments have been employed to characterize the compounds. 1D NOE experiments have been useful in understanding the structure of 1,3,5-tris(N-methylenzimidazolyl)benzene.