Synthesis of a new hetrocyclic system 7,8-dihydroimidazo[1,2-<Emphasis Type="Italic">c</Emphasis>][1,3]oxazolo[4,5-<Emphasis Type="Italic">e</Emphasis>]pyrimidine

2-(Acylaminocyanomethylene)imidazolidines are formed on interacting 2-acylamino-3,3-dichloro-acrylonitriles with ethylenediamine. The former are converted into new derivatives of oxazolo-[4,5-e]pyrimidine on treatment with trifluoroacetic acid, and then with triethyl orthoformate.     

Synthesis of tricyclic pyrido[2,3‐b][1,4]‐thiazines via nucleophilic substitution of activated precursors

Pyrido‐anellated compounds analogous to tricyclic 1,4‐benzothiazine derivatives were synthesized. Thus, under mild reaction conditiones substitution of thiolactim 3 with different N‐nucleophiles yielded the precursors for compounds, which were cyclized in a further step to the corresponding tricyclic derivatives.     

Synthesis and thermal rearrangement of 2-(2-chloroethoxy)-4,6-disubstituted <Emphasis Type="Italic">sym</Emphasis>-triazines

On thermolysis of 4-methoxy- and 4-alkylamino-2-(2-chloroethoxy)-6-morpholino(piperidino)-sym-triazines, the corresponding oxazolo- or imidazo-sym-triazinones are formed by elimination of methyl chloride or hydrogen chloride, and 4,6-disubstituted 3-(2-chloroethyl)-sym-triazin-2-ones are formed from 4,6-dimorpholino(dipiperidino) derivatives.     

Photochemische Umwandlungen. XVIII Photochemische Isomerisierung annellierter Oxanorbornadiene Vorläufige Mitteilung

Photochemical cycloaddition reactions in anellated oxanorbornadiene derivatives have been investigated. In the case of 7a the tetracyclic isomer 8a can be isolated which adds dimethylacetylenedicarboxylate in the manner of a bis-homo-furan system. On thermal activation 8a yields the thiepino-oxepin derivative 9a. In contrast, on direct photoexcitation of the benzoxanorbornadiene the primary photoproduct cannot be identified, the reaction leading directly to the benz[d]oxepin.     

New electrophilic reactions of 2,2′-bisindolyls with acid chlorides and carbodienophiles

Some new acylation and cyclization reactions of 2,2′-bisindolyls 1, 2 are described. The product patterns constitute acyl derivatives 3, 4, 5 and an aldehyde 7 , indolo[2,3-a]carbazoles 6, 14, 17, 19, 20 and cyclopentadiindoles 22 and 24 . In the reaction with aryne or diazotated anthranilic acid, a 3-benzoylindole derivative 9 and phenylindolyl azo dye 10 are formed. N-methylmaleimide reacts with 2,2′-bisindolyl 2 via Michael type addition, dehydrogenation and cyclization to several functionalized or anellated indole derivatives 11, 12, 13 and 14 , respectively.     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

Saturated heterocycles. Part 216 . Synthesis,structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-c were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b , the thiones 4a,b , the urea derivatives 5a,b , and N-acylated compounds 6a-e . Compounds 6b,d were ring-opened by hydrochloric acid in ethanol to yield trans-2-(1-carbethoxyethoxy)-1-acylaminomethylcyclohexane derivatives 7b,d . The ¹H- and ¹³C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the trans anellated compounds have a chair conformation.     

Bis[1]benzothieno[1,4]thiazines: Planarity,Enhanced Redox Activity and Luminescence by Thieno-Expansion of Phenothiazine

Twofold Buchwald–Hartwig aminations selectively furnish three regioisomers of bis[1]benzothieno[1,4]thiazines; X-ray structure analyses and DFT calculations were corroborated for correlation of their electronic properties. All regioisomers outscore the parent compound phenothiazine with respect to a low-lying oxidation potential and reversible redox activity. The anti-anti bis[1]benzothieno[3,2-b:2′,3′-e][1,4]thiazines possess the lowest oxidation potentials in this series and displayed pronounced green luminescence in solution (Φ_F≈20 %) and in the solid state. Syn-anti regioisomers were only weakly luminescent in solution, but showed aggregation-induced emission enhancement and solid-state luminescence. Most interestingly, X-ray structure analyses revealed that anti-anti derivatives have an amazingly coplanar structure of the pentacyclic anellated 1,4-thiazine system, emphasizing a structural similarity to heteroacenes. The calculated theoretical nucleus-independent chemical shifts additionally suggested that these 8π-electron core systems can be considered as the first electronically unbiased anellated 1,4-thiazines with antiaromatic character.     

Palladium-catalyzed [2 + 2 + 2] cocyclotrimerization of benzynes with bicyclic alkenes: an efficient route to anellated 9,10-dihydrophenanthrene derivatives and polyaromatic compounds

An efficient method for the cocyclotrimerization of bicyclic alkenes and benzynes catalyzed by palladium phosphine complexes to give the corresponding norbornane anellated 9,10-dihydrophenanthrene derivatives is described. Bicyclic alkenes 1a-i undergo [2 + 2 + 2] cocyclotrimerization with benzynes generated from precursors 2a-d [2-(trimethylsilyl)phenyl triflate (2a), 4,5-dimethyl-2-(trimethylsilyl)phenyl triflate (2b), 6-(trimethylsilyl)-2,3-dihydro-1H-5-indenyl triflate (2c), 4-methyl-2-(trimethylsilyl)phenyl triflate (2d)] in the presence of PdCl(2)(PPh(3))(2) in acetonitrile at ambient temperature to yield anellated 9,10-dihydrophenanthrene products 3a-r in moderate to excellent yields. The [2 + 2 + 2] cocyclotrimerization products from oxa- and azabicyclic alkenes can be applied for the synthesis of polyaromatics, substituted benzo[b]triphenylenes (8a-f), via a simple Lewis acid mediated deoxyaromatization in good yields. In addition the [2 + 2 + 2] products undergo retro Diels-Alder reaction readily, providing a new method for the synthesis of substituted phenanthrenes and for generating isobenzofurans. A plausible mechanism is proposed to account for the catalytic [2 + 2 + 2] cycloaddition reaction.     

Asymmetric rhodium-catalyzed hydrogenation meets gold-catalyzed cyclization: Enantioselective synthesis of 8-hydroxytetrahydroisoquinolines

Different furyl-substituted (Z)-dehydroamino acid derivatives were hydrogenated with the rhodium/Mandyphos(OMe)-system to give enantiomeric excesses between 80 and 98 %. The absolute configuration of the newly formed stereogenic center was determined by anomalous diffraction to be R. These chiral furyl alanines were transferred into 8-hydroxytetrahydroisoquinolines by employing gold-catalyzed arene synthesis as the key step. During the latter reaction sequence, also including either a propargylation or a reduction, a protection of the hydroxy group, and a subsequent propargylation, no racemization of the stereogenic center was observed. With very electron-rich furans, instead of the 8-hydroxytetrahydroquinolines as products, furans anellated to seven-membered rings with exocyclic C-C double bonds are formed under the same reaction conditions.     

Novel Ring Systems: Spiro[Cycloalkane] Derivatives of Triazolo- and Tetrazolo-Pyridazines

In orderto synthesize new pyridazine derivatives anellated with different nitrogen heterocyclic moieties, spiro[cycloalkane]pyridazinones were transformed into the corresponding thioxo derivatives via a reaction with phosphorus pentasulfide. The reaction of the formed 2,3-diazaspiro[5.5]undec-3-ene-1-thiones with hydrazine provided the corresponding 1-hydrazono-2,3-diazaspiro[5.5]undec-3-ene, whose diazotization led to the desired spiro[cyclohexane-1,8′-tetrazolo[1,5-b]pyridazines. The reaction of dihydropyridazinethiones with benzhydrazide afforded the corresponding 7H-spiro[[1,2,4]triazolo[4,3-b]pyridazin-8,1′-cyclohexanes]. As a result of our work, seven new pyridazinethione intermediates were prepared, which served as starting materials for the synthesis of two kinds of new ring systems: tetrazolo-pyridazines and triazolo-pyridazines. The six new annulated derivatives were characterized by physicochemical parameters. The new N-heterocycles are valuable members of the large family of pyridazines.     

Synthesis of methyl 2-aryl-5-chlorosulfonyl-1,3-oxazole-4-carboxylates and their reactions with amines and amidines

Previously unknown methyl 2-aryl-5-chlorosulfonyl-1,3-oxazole-4-carboxylates have been synthesized. Their reactions with amines and amidines have yielded the corresponding sulfonamides and 6H,7H-[1,3]oxazolo-[5,4-d]pyrimidin-7-ones.     

Trennprobleme bei strukturisomeren 2-Aminobenzophenonen als Zwischenprodukte zur Darstellung anellierter 1,4-Benzodiazepine

Ohne Zusammenfassung

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Problems in the separation of isomeric 2-aminobenzophenones as intermediates in the preparation of anellated 1,4-benzodiazepines

     

Polyfunctional pyridines from nitroacetamidine and β-diketones. A useful synthesis of substituted imidazo [4,5-b] pyridines and related compounds

Nitroacetamidine undergoes a useful cyclocondensation with β-diketones to produce substituted 2-amino-3-nitropyridines. Use of an acylpyruvate generates hitherto unreported 2-amino-3-nitropyridine-4-carboxylates. These may be converted easily to functionalized imidazo[4,5-b]pyridines and oxazolo-[5,4-b]pyridines.     

Quaternary salts of alkaloids

New biologically active quaternary salts of the alkaloids ajmaline, quinine, hyoscyamine, codeine, and strychnine were synthesized. So-called separable conformers were observed among the ajmaline derivatives. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 381–383, July–August, 2006.     

Influence of anellation in N-heterocyclic carbenes: novel quinoxaline-anellated NHCs trapped as transition metal complexes

The synthesis, NMR-, and crystal structure data of novel electron-deficient quinoxaline anellated imidazol-2-ylidene precursors and complexes thereof are reported and compared with related less electron-withdrawing or non-anellated N-heterocyclic carbenes and complexes to illustrate anellation effects.     

Carbon-13 n.m.r. spectroscopy of some Strychnos alkaloids

¹³C N.m.r. spectra have been determined for strychnine and a series of fourteen derivatives. The assignments are based on previously established data and on off-resonance decoupled spectra. The shifts resulting from the alterations in molecular structure are discussed and explained, in part, as a consequence of conformational changes. This detailed study indicates that changes are required in some previously published assignments.     

Anellated N-heterocyclic carbenes: 1,3-dineopentylnaphtho[2,3-d]imidazol-2-ylidene: synthesis, KOH addition product, transition-metal complexes, and anellation effects

Two novel anellated N-heterocyclic carbenes (NHC), 1,3-dineopentylnaphtho[2,3-d]imidazol-2-ylidene, and 1,3-dineopentyl-2-ylido-imidazolo[4,5-b]pyridine were obtained by reduction of the respective thiones with potassium, the former also by deprotonation of the corresponding naphthimidazolium hexafluorophosphate by using excess KH in THF. The use of equimolar amounts of KH provided an unexpected formal addition product of this NHC with KOH. X-ray crystal structure analysis of the adduct provided evidence for a distorted tetrameric N-heterocyclic alkoxide, stabilized by two THF molecules. In C(6)D(6) the compound undergoes disproportionation. Transition-metal complexes [(NHC)AgCl], [(NHC)Rh(cod)Cl], and (E)-[(NHC)(2)PdCl(2)] of the novel naphthimidazol-2-ylidene were synthesized. X-ray crystal structures and (1)H and (13)C NMR spectroscopic data provided detailed structural information. Comparing characteristic data with those of nonanellated and differently anellated NHCs or their complexes provides information on the influence of the extended anellation.     

Preparative separation and purification of two highly polar alkaloids derived from Semen Strychni extracted with dichloromethane by high‐speed countercurrent chromatography

Brucine chloromethochloride and strychnine chloromethochloride, the two chloromethochloride derivatives formed during the extraction of Semen Strychni in which dichloromethane was used as the extracting solvent, were isolated and purified by high‐speed countercurrent chromatography for the first time. The two‐phase solvent system composed of chloroform/methanol/0.3 mol/L hydrochloric acid (4:3:2, v/v/v) was selected for separation. From 300 mg of the crude extracts, 56.2 mg of brucine chloromethochloride and 60.2 mg of strychnine chloromethochloride were obtained with the purity of 99.78 and 96.99%, respectively, and the structures were confirmed by mass spectrometry, ¹H, ¹³C, and two‐dimensional NMR spectroscopy. The results indicated that the present method is a powerful technology for large‐scale isolation of alkaloids from Semen Strychni.     

Anticonvulsant activity of 3-oxo-5-substituted benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-pyridazinylacetylhydrazides

A series of 3-oxo-5-substituted-benzylidene-6-methyl-(4H)-2- pyridazinylacetamides and 2-pyridazinylacetylhydrazides were synthesized and evaluated for anticonvulsant activity against electrically and chemically induced seizures. In the maximal electroshock-induced seizures test, most of the derivatives showed an anticonvulsant effect better than that of sodium valproate, a commonly used anticonvulsant drug. At 100 mg/kg orally, compounds 5a and 5b respectively protected 50 and 60% of the mice against pentylentetrazole-induced seizures. In addition, these two derivatives showed significant anticonvulsant properties at doses that did not produce ataxia or sedation. The title compounds were also tested for their ability to antagonize convulsions induced by bicuculline and strychnine. Their effect on tremors induced by oxotremorine in mice was also evaluated.