Zur Chemie der 5-Alkylamino-4H-thiopyrano[2,3-b]pyridin-4-one

4-Alkylaminopyridinethiones · HCl (1 · HCl) react with bis-trichlorethylmalonate (3) predominantly to 5-alkylamino-4H-thiopyrano [2,3-b]pyridine-4-ones (6). With alcohols in the presence of acids at 25°C6 undergoes an alcoholysis to the corresponding alkyl-3-(2-thioxo-3-pyridyl)propionates (9). On heating in dilute alkali6 is hydrolysed via 4-alkylamino-2-thioxopyridyl-propylketones (11) to the tautomers, 4-hydroxy-2-thioxopyridylpropylketone (12 A) and 2-thioxo-3-(1-hydroxybutenyl)-4-piperidon (12 B), resp. On refluxing with alkali the ethyl-pyridylpropionate9 a is cyclisized to the 1-alkyl-1,6-naphthyridine-2(1H)-one (4 a), but boiling in ethanolic acid hydrolyses9 a via the pyridylpropionic acid10 to 4-alkyl-aminopyridylpropylketone (11 a). The latter can be transformed via the tautomers12 A,B and 2-methylthio-3-pyridylpropylketone (13) to the 4-hydroxy-3-butyrylpyridone (14 A) and its tautomer, 3-(1-hydroxy-butenyl)-piperidine-2,4-diones (14 B) resp. The structure of14 A,B is established by reaction of 4-isopropylamino-2(1H)-pyridone (2) with butanoylchloride to the 4-isopropylamino-3-butyrypyridone (15) and hydrolysis of15 to the tautomers14 A,B.     

Synthese von (5,10)-(7,8)-Bisepoxiden aus α- und β-4-Phenyl-1,2,4-triazolin-3,5-dion-Addukten von Vitamin D3 und Röntgenstrukturanalyse eines der Benzoylderivate

Oxidation of the α- and β-4-phenyl-1,2,4-triazolin-3,5-dione adducts of vitamin D₃ (2 and1) withMCPBA yields two diastereomeric mixtures of the (5,10)-(7,8)-dioxiranes3 a,3 b,3 c and4 a,4 b respectively. The corresponding benzoates5 a,5 b,6 a and6 b were prepared and the X-ray crystal structure of5 b was determined. This analysis proved5 b to be the (5R, 1 OS)-(7R, 8R)-dioxirane of the β-resp. (6S)-4-phenyl-1,2,4-triazolin-3,5-dione adduct1 of vitamin D₃.     

Synthesis and characterization of a series of chiral NHC–Pd complexes derived from l-phenylalanine

The synthesis of a series of chiral Pd(L)PyBr₂ (3a–3e) and Pd(L)PyCl₂ (4d and 4e) complexes from l-phenylalanine is presented (L = (S)-3-allyl-4-benzyl-1-(2,6-diisopropylphenyl)-imidazolin-2-ylidene (a), (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(naphthalen-2-ylmethyl)imidazolin-2-ylidene (b), (S)-4-benzyl-3-(biphenyl-4-ylmethyl)-1-(2,6-diisopropylphenyl)imidazolin-2-ylidene (c), (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(naphthalen-1-ylmethyl)imidazolin-2-ylidene (d) or (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(2,4,6-trimethylbenzyl)imidazolin-2-ylidene (e). The complexes were characterized by physicochemical and spectroscopic methods, and the X-ray crystal structures of 3a–3c and 4d are reported. In each case, there is a slightly distorted square-planar geometry around palladium, which is surrounded by imidazolylidene, two trans halide ligands and a pyridine ligand. There are π–π stacking interactions in the crystal structures of these complexes. Complex 3a showed good catalytic activity in the Cu-free Sonogashira coupling reaction under aerobic conditions.     

Syntheses, characterization and crystal structures of new mono- and bis-Schiff base compounds derived from 1,2,4-triazine and the silver(I) complexes containing mono-Schiff base ligands

Some new Schiff bases, (Z)-4-amino-3-((E)-(R-methoxybenzylidene)hydrazono)-6-methyl-3,4-dihydro-1,2,4-triazin-5(2H)-one (R?=?2 (L2), R?=?3 (L3) and R?=?4 (L4)), were synthesized by the condensation reactions of 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5(4H)-one (L1) and corresponding methoxybenzaldehyde in a molar ratio 1:1.5 in high yields. The reaction of L2 and L4 with an excess amount of the corresponding aldehydes gave the unsymmetrical bis-Schiff bases (E)-3-((E)-(R-methoxybenzylidene)hydrazono)-4-((E)-R-methoxybenzylideneamino)-6-methyl-3,4-dihydro-1,2,4-triazin-5(2H)-one (R?=?2 (L22) and R?=?4 (L44)), respectively. Furthermore, the reaction of L2?CL4 with silver(I) nitrate in a molar ratio 2:1 led to the silver(I)-complexes with the general formula [Ag(Lx)₂]NO₃ (Lx?=?L2 (2), L3 (3) and L4 (4)). All synthesized Schiff base compounds and complexes were characterized by a combination of IR-, ¹H-NMR spectroscopy, mass spectrometry and elemental analyses. In addition, the structures of L2, L4·CH₃CN, L22·CH₃OH and L44·CH₃OH and complexes 2 and 4 were determined by X-ray diffraction studies.     

The first example of asymmetric Michael reaction catalyzed by chiral alkali metal alkoxides

Some chiral sodium alkoxides can be used as catalysts in the asymmetric Michael reaction as exemplified by the 1,4-addition of an achiral Ni^II complex of the Schiff base derived from glycine andN-(2-pyridylcarbonyl)-o-aminobenzophenone (1) to methyl methacrylate (2) or methyl acrylate (14). The products of the reaction of1 with2,viz., the corresponding diastereomeric complexes of 4-methylglutamic acid, are formed in dissimilar amounts (de 26–85%); theee value for the major diastereomer (2S,4R)-3a is 28%. After recrystallization, the enantiomeric purity of complex3a increases toee>85%. Acidcatalyzed hydrolysis of the enantiomerically enriched complex3a affords (2S,4R)-4-methylglutamic acid (ee>85%). The complex of glutamic acid15 resulting from the reaction of1 with14 is formed with anee of 45%. After recrystallization, the enantiomeric purities of complex15 and glutamic acid increase toee>90%.     

Isomere Diamino-alkoxy-pyridin-carbonitrile — ihre Trennung und Verwendung als Kupplungskomponenten

The isomeric 4,6-diamino-2-alkoxy- (3), and 2,4-diamino-6-alkoxy-3-pyridine-carbonitriles (4) are obtained by treatment of 2-amino-1,1,3-tricyanopropene (1) with sodium alkoxides. Separation is based on their differentpK _a -values (3 a=2.01,4 a=4.17). Coupling reaction of3 a-c with benzenediazonium chloride in strong acidic medium leads to the yellow azo dyes5 a-c, whereas coupling of4 a requires a buffered solution (pH 4–6) to yield6. The UV-VIS spectra of the isomer pyridines and the azo dyes are discussed.     

Synthese von 1-substituierten 4-Amino-2(1H)-pyridinthionen durchDimroth-Umlagerung aus 2,4-Diaminothiopyranyliumhalogeniden

4-Amino-2-alkylimino-2H-thiopyranes (5) and 4-amino-2-alkylaminothiopyranylium halogenides (4) resp. on heating in refluxingDMFA are rearranged in the presence of Na-ethylate to 1-alkyl-4-aminodihydro-2(1H)-pyridinethiones (2). Also 2-methylthiothiopyranylidenammonium iodides (6) and 2-methylthio-4H-thiopyrane-4-one (7) can be transformed into 1-substituted 2(1 H)-pyridinethiones (2) by heating in prim. amines. On treatment with alkali. 4-dimethylaminothiopyranylium iodide (4 a) is transformed into its base5 a and hydrolyzed to8. 5a and8 are rearranged to the pyridinethiones2 a and the tautomers9 A,B. The structure of the rearranged pyridinethiones2 was proved by the1-phenylderivate2 a. Thus 4-methyl-3-penten-2-on reacts with phenylthiourea via the phenylimino-1,3-thiazine (14) to give 3-phenyl-2(1H)pyridinethione (15).15 is transformed by themethylpyrimidine-pyridine-rearrangement to the 1-phenylpyridinethione2 a. The mechanism of theDimroth-reaction of 2-alkylimino-2H-thiopyranes (5) and the stereochemistry of the1-benzyl-6-phenyl-2(1H)-pyridinethiones2 are discussed.     

One-pot microwave-assisted solvent-free synthesis,theoretical and experimental studies on barrier rotation of C–N bond of N-alkenyl-1,2,3-triazoles

The reactions on benzotriazoles continue to happen to reach interesting varieties of their derivatives. This study reports a fast one-pot microwave-assisted solvent-free synthesis of N-alkenyl-1,2,3-benzotriazole (3, 5, and 7) and 1-(2-Alkyloxycarbonyl-vinyl)-1H-[1–3] triazole-4-carboxylic acid methyl ester (8 and 9) derivatives by nucleophilic addition reactions of 1,2,3-benzotriazole (C₆H₅N₃) (1) and 1H-[1–3] triazole-4-carboxylic acid methyl ester (C₄H₄N₃O₂) (1′) with R-propiolates (R = Me, Et; 2 & 4) and phenylacetylene 6 in good yields. The values of activation energy for rotation around C–N bond in the synthesized N-alkenyl-1,2,3-triazole compounds were studied by DFT-B3LYP/6-31G* method.     

Amino(tert-butyl-NNO-azoxy)furoxans: synthesis, isomerization, and rearrangement of N-acetyl derivatives

3-Amino-4-(tert-butyl-NNO-azoxy)furoxan (1a) and 4-amino-3-(tert-butyl-NNO-azoxy)-furoxan (1b) and their acetyl derivatives 6a,b were obtained. The equilibria 1a ai 1b and 6a ? 6b were studied. Furoxan 6b can undergo thermal rearrangement into 3-[(tert-butyl-NNO-azoxy)(nitro)methyl]-5-methyl-1,2,4-oxadiazole (7), prolonged heating of which gives N-(2-tert-butyl-5-nitro-1-oxido-2H-1,2,3-triazol-4-yl)acetamide (8). With the transformation 7 → 8 as an example, the possibility of participation of the azoxy group in the Boulton-Katritzky rearrangements was demonstrated for the first time.     

Helix-sense-selective radical polymerization of bulky styrenic monomers: chiral induction and liquid crystallinity

Eight chiral vinylterphenyl monomers,(+)-2,5-bis{4′-[(S)-1″-methylpropyloxy]phenyl}styrene(Ia),(+)-2,5-bis{4′-[(S)-2″-methylbutyloxy]phenyl}styrene(Ib),(+)-2,5-bis{4′-[(S)-3″-methylpentyloxy]phenyl}styrene(Ic),(+)-2,5-bis{4′-[(S)-4″-methylhexyloxy]phenyl}styrene(Id),(?)-2,5-bis{4′-[(R)-1″-methylpropyloxy]phenyl}styrene(Ie),(+)-2-{4′-[(S)-1″-methylpropyloxy]phenyl}-5-{4′-[(R)-1″-methylpropyloxy]phenyl}styrene(IIa),(?)-2-{4′-[(R)-1″-methylpropyloxy]phenyl}-5-{4′-[(S)-1″-methylpropyloxy]phenyl}styrene(IIb),and(+)-2-{4′-[(S)-2′′-methylbutyloxy]phenyl}-5-{4′-[(S)-1″-methylpropyloxy]phenyl}styrene(III),were synthesized and radically polymerized.These molecules were designed to further understand long-range chirality transfer in radical polymerization and to possibly tune the chiroptical properties of the polymers by varying the spatial configuration,position,and various combination of the stereogenic centers at the ends of p-terphenyl pendants.The resultant polymers adopted helical conformations with a predominant screw sense.When the stereogenic centers ran away from the terphenyl group as in Ib?d,the corresponding polymers changed the direction of optical rotation in an alternative way and showed no obvious stereomutation upon annealing in tetrahydrofuran.The two stereogenic centers of IIa,IIb,and III acted concertedly in chiral induction,whereas those of Ia and Ie played a counteractive role.The five polymers derived from Ia,Ie,IIa,IIb,and III underwent stereomutation when annealed in tetrahydrofuran.The polymers PIa?e had good thermal stability and high glass transition temperatures(Tgs).They generated liquid crystalline phases at above Tgs that could be kept upon cooling,with the exception of PIe.This result was consistent with the extended helical structures.     

Anion-directed organized assemblies of protonated pyrazole-based ionic salts

The reactions of 3(5)-(4-methoxyphenyl)-5(3)-phenyl-1H-pyrazole (L ¹ ) with nitric acid and 5-(4-benzyloxyphenyl)-3-(furan-2-yl)-1H-pyrazole(L ² ) with hydrochloric acid produced [HL ¹ · NO₃] (Salt-1) and [HL ² · Cl] (Salt-2). The structures of Salt-1 and Salt-2 were determined by single crystal X-diffraction. In Salt-1, HL ¹ showed [2 + 2] binding of NO₃ ^? ions in the solid state to form dimer architecture with R ₁ ² (4) and R ₄ ⁴ (14) graph sets. An anion directed one-dimensional anion-assisted helical chain with active participation of the chloride ion and protonated pyrazole via N–H···Cl hydrogen bonding in Salt-2. In addition, the protonated HL ² molecules interacted with each other through weak C–H···π interactions resulting in the formation of another one-dimensional helical chain.     

Chemie des 5,7-Dihydroxy-2H-thiopyrano[2,3-b]pyridin-4(3H)-ons

Hydrolysis of the 4-alkyliminothiopyrano[2,3-b]pyridinedioles (5) and 4-alkylaminothiopyrano[2,3-b]pyridones (6) resp. with 10% NaOH gives 5,7-dihydroxy-2H-thiopyrano[2,3-b]pyridine-4(3H)-one (7).7 can be obtained in better yield by reaction of 4-dimethylamino-2(1H)-pyridinethione (8) with bistrichlorphenylethylamlonate (2). Aminolysis of7 affords the two isomeric products5 and6. On treatment with hydrazines,7 reacts only to 4-hydrazonoderivatives5. By heating in bromobenzene5d is cyclisized to 1H-5,1,2,6-thiatriaza-acenaphthylen-7-ol (11). On methylation with methyljodide5,6 and7 furnish the 7-methoxyproducts13,14 and12. By heating in 20% NaOH7 is transformed into the 2-thioxo-3-pyridylmethylketone16 A and its tautomer, 2-mercapto-3-pyridylmethylketone16 B. The structures of5,6 and7 are discussed.     

Construction and characterization of novel molecular architectures through coordination-driven self-assembly: rhomboid and overlapped double rhomboid

The potentially tridentate ligands 4-(6-(pyridin-4-yl)pyridin-2-yl)pyridine (4) and 3-(6-(pyridin-3-yl)-pyridin-2-yl)pyridine (5) have been prepared and characterized. From the self-assembly of 4 or 5 and 2,9-bis[trans-Pt(PEt₃)₂(NO₃)]phenanthrene (6), two supramolecular platinum-based macrocycles with rhomboid (7) and overlapped double rhomboid (8) structures have been constructed. Compounds 7 and 8 are formed in different shapes due to the different nitrogen positions (meta and para) of the ligands 4 and 5, respectively. Both supramolecules are characterized by multinuclear NMR and electrospray ionization mass spectroscopies.     

Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen

<正>1 General procedure for the preparation of 3-substituted glutaronitriles To a 100 mL flask containing aldehyde(30 mmol) and cyanoacetic acid(10.20 g, 120 mmol) was added 4-methylpiperidine(0.4 mL) and 23 mL N-methylmorpholine. The reaction mixture was warmed to mild reflux for 24 h and then cooled to room temperature and concentrated on a rotary evaporator. The resulting mixture was dissolved in 100     

A convergent paired electrochemical synthesis of new heterocyclic compounds. Reaction of benzoquinones with 3-Amino-4-hydroxycoumarin

Electrochemical oxidation of catechols (1) has been studied in the presence of cathodically generated 3-amino-4-hydroxycoumarin (3a) as a nucleophile in aqueous solutions, using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-benzoquinones derived from catechols (1) participate in Michael addition reaction with 3-amino-4-hydroxycoumarin (3a) to form the corresponding new heterocyclic compounds (7) (oxidized form of coumestan derivatives). The electrochemical process consists of a multi-step including (a) cathodic reduction of 4-hydroxy-3-nitrocoumarin (3) to 3-amino-4-hydroxycoumarin (3a), (b) anodic oxidation of catechols (1) to related o-benzoquinone (2), (c) the Michael addition reaction of 3-amino-4-hydroxycoumarin (3a) to o-benzoquinone (2), and (d) anodic oxidation of formed adduct. The paired electrochemical synthesis of compounds 7a and 7b has been successfully performed in a one-pot process at carbon rods as working and counter electrodes in an undivided cell.     

Chinolizine und Indolizine,XIV Umlagerungen von Heterocyclen,X Ringumwandlungen von 1-Acyl-2-hydroxy-4-chinolizinonen

By heating with ammonia or aniline 1-acyl-2-hydroxy-4-quinolizinones (1 a–e) are transformed to 4-hydroxy-5-(2-pyridyl)-2-pyridones (3 a–f), with4 a–d as minor sideproducts. The structure of the rearranged compound3 f was established by an independent synthesis starting with6 and7. The reaction of1 a, d with ethyl β-aminocrotonate (β-ACE) yields pyrono-quinolizinones8 a, b and pyronopyridones9 a, b as byproducts; the latter are obtained in high yield by reaction of3 a, b with β-ACE. The ringtransformation reaction cannot be extended to 1-methoxycarbonyl-quinolizinones, such as10; in this case 2-amino-4-quinolizinone11 is the main product of the reaction with ammonia.     

Syntheses based on 1-iodo-7-(dioxonium)decahydro-closo-dodecaborate

The nucleophilic cleavage of 1-iodo-7-(dioxonium)decahydro-closo-dodecaborate (1) with sodium azide and thymidine or guanosine derivatives was studied. Compound 1 exhibits higher reactivity compared to the unsubstituted dioxonium derivative. The reactions of 1[NBu4] with 3′,5′-di(tert-butyldimethylsilyl)thymidine and 8-mercaptoguanosine afford the corresponding boron-containing nucleosides.     

Tribromogermyl monochelates — derivatives of N,N-disubstituted 2-hydroxycarboxylic amides

Reactions of GeBr₄ with N,N-dimethyl-2-trimethylsiloxypropionamide (2a), (S)-2-trime-thylsiloxypropionpyrrolidide ((S)-2b), and N,N-dimethyl-O-(trimethylsilyl)mandelamide (2c) afforded pentacoordinated neutral (O,O)-monochelates, viz., N,N-dimethyl-2-tribromoger-myloxypropionamide (3a), (S)-2-tribromogermyloxypropionpyrrolidide ((S)-3b), and N,N-dimethyl-O-(tribromogermyl)mandelamide (3c), respectively. X-ray diffraction study was performed for tribromides 3a, (S)-3b, and 3c, as well as for the N,N-dimethylmandelamide (1c) described earlier. According to the X-ray diffraction data, the Ge atom in tribromides 3a, (S)-3b, and 3c is pentacoordinated and has trigonal bipyramidal configuration with two halogen atoms and oxygen atom of the ether group in the equatorial positions and the halogen atom and the amide oxygen atom in the axial fragment, the bonds in which are somewhat longer as compared to the analogous bonds in tetracoordinated Ge compounds.     

Synthesis and characterization of 2-alkyl -5-{4-[(3-nitrophenyl-5-isoxazolyl)methoxy]phenyl}-2H-tetrazoles

Heteroaryl substituted analogs of antirhnoviral (A), was prepared by a convergent approach. 3-Nitrophenyl-5- bromooromethylisoxazoles 5a–b were synthesized by [3+2] cycloaddition of 3-(benzoyloxy)-propyne 2 to in situ generated arylnitrile oxides followed by deprotection of cycloadducts 3a–b and bromination of the resulting alcohols 4a–b. Coupling of 3- nitrophenyl-5-bromooromethylisoxazoles (5a–b) with 4-[5-(2-alkyl-2H-tetrazolyl)]phenols (6a–d) in N-methylpyrrolidinone under mild conditions afforded a new series of 2-alkyl-5-{4-[1-(3-nitrophenyl-5-isoxazolyl)methyloxy]phenylr}-2H-tetrazoles (7a–h) in high yields. The structures of the synthesized compounds were confirmed by their ¹H NMR, Mass spectral, and Elemental Analysis data.     

Two efficient methods for the synthesis of novel indole-based chalcone derivatives

Two powerful methods for the synthesis of indole-based chalcone derivatives, namely (E)-1-(2-chloro-1-(4-chlorobenzyl)-1H-indol-3-yl)-3-aryl(hetaryl)prop-2-en-1-ones (3a–l), are described, involving the ultrasound-assisted or solvent-free Claisen–Schmidt condensation reaction of 3-acetyl-2-chloro-1-(4-chlorobenzyl)indole (1) and various aromatic aldehydes (2a–l). The ultrasound-assisted Claisen–Schmidt condensation reaction was carried out using 1,4-dioxane as solvent and KOH as base at room temperature to give the corresponding products (3a–l) in yields ranging from 75 to 88 %. Alternatively, the Claisen–Schmidt condensation reaction could also be conducted under solvent-free conditions to obtain the products (3a–l) in comparable yields. The two procedures offer easy access to indole-based chalcone derivatives in short reaction times and good yields under mild conditions. Particularly, the advantageous aspect of the solvent-free method could avoid the use of environmentally hazardous and toxic solvents, and also reduced costs. The structures of all the newly synthesized indole-based chalcones 3a–l were confirmed by spectral data and elemental analyses.