Synthesis and redox-enzyme modulation by amino-1,4-dihydro-benzo[d][1,2]dithiine derivatives

A convenient method to prepare a series of benzodithiine derivatives was developed, via the synthesis of cyclic disulfide building blocks containing an amino-group linker. Some of the novel cyclic disulfide compounds are shown to modulate the activity of the redox-enzyme glutathione reductase.     

Microwave-assisted one-pot synthesis of benzo[b][1,4]oxazin-3(4H)-ones via Smiles rearrangement

An efficient method for the synthesis of benzo[b][1,4]oxazin-3(4H)-ones via Smiles rearrangement using a microwave-assisted one-pot, three-step reaction has been developed. Various benzo[b][1,4]oxazin-3(4H)-ones are obtained in good yields (55-86%) from the corresponding substituted 2-chlorophenols and primary amines in short reaction time (18-40 min).     

A one-pot synthesis of pyrido[2,3-b][1,4]oxazin-2-ones

Pyrido[2,3-b][1,4]oxazin-2-ones are conveniently prepared in excellent yields by a one-pot annulation of N-substituted-2-chloroacetamides with 2-halo-3-hydroxypyridines with use of cesium carbonate in refluxing acetonitrile. The key transformation features a Smiles rearrangement of the initial O-alkylation product and subsequent cyclization.     

Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-ones via Smiles rearrangement

The synthesis of benzo[b][1,4]thiazin-3(4H)-one derivatives in a simple and efficient method from the one-pot reaction of substituted 2-chlorobenzenthiols, chloroacetyl chloride, and primary amines via Smiles rearrangement under microwave irradiation gave high yields (65-92%) of the products with short reaction time (15-20 min).     

Novel synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones

A novel and effective synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones via Smiles rearrangement is presented. Treatment of N-substituted 2-chloro(or hydroxy)acetamide, 2-tetrahydropyranyl-4-chloro-5-hydroxy(or chloro)pyridazin-3-one and cesium carbonate in refluxing acetonitrile was afforded the corresponding pyridazino[4,5-b][1,4]oxazin-3,8-diones in excellent yield.     

[bmIm]OH: an efficient basic catalyst for the synthesis of 4H-benzo[d][1,3-]oxazin-4-one derivatives in solvent-free conditions

Reusable [bmIm]OH was found to be a highly efficient renewable homogenous catalyst for the rapid and convenient synthesis of benzoxazine-4-one derivatives from o-iodobenzoic-acid and benzonitrile at 75 °C in moderate to good yields. This methodology provides a facile and straightforward path to construct other related heterocycles in an eco-compatible fashion.     

Synthesis of novel substituted naphthoquino[b]-benzo[e][1,4]diazepines via Pictet-Spengler cyclization

Synthesis of novel 4,5-dihydro-1H-1,4-naphthoquino[b]-benzo[e][1,4]diazepine derivatives via Pictet-Spengler cyclization is reported. Reaction of 2,3-diamino-naphthoquinones with aldehydes in the presence of BF₃·Et₂O gives benzodiazepine-naphthoquinones in good yields.     

Synthesis of 1,3-diaminated stereotriads via rearrangement of 1,4-diazaspiro[2.2]pentanes

The synthesis of 1,3-diaminated stereotriads via the bis-aziridination of allenes is reported. The reactive 1,4-diazaspiro[2.2]pentane intermediates undergo a mild Br?nsted acid-promoted rearrangement to yield 1,3-diaminated ketones in good yields with excellent stereocontrol. Directed reduction of the ketone can be achieved to yield a C-N/C-O/C-N stereotriad in high dr. The ability to transfer the axial chirality of the substrates to the products allows for the facile preparation of enantioenriched stereotriads from allenes in two simple steps.     

Synthesis of indeno[2,1-b][1,4]benzothiazine derivatives from 2-bromoinden-1-ones

2-Bromoinden-1-ones 2 were condensed with 6-substituted 3-aminopyridine-2(1H)-thiones to produce a new type of 4-azaindeno[2,1-b][1,4]benzothiazine derivatives 3 . Substituted 6-phenylindeno[2,1-b][1,4]benzothiazines 4 were also prepared by reacting 2-bromo-5-methoxy- and 2,6-dibromo-5-methoxyinden-1-ones with o-aminobenzenethiol.     

Asymmetric hydrogenation of 3-methylbenz[b][1,4]oxazin-2-ones catalyzed by iridium complexes with phosphite-type ligands

Russian Chemical Bulletin - The chiral amidophosphite ligand in the iridium-catalyzed hydrogenation of 3-methylbenz[b][1,4]oxazin-2-ones in ethanol provides higher conversion and enantioselectivity...     

Synthesis of pyrimido[4,5-e][1,4]oxazepin-5-ones

Eighteen novel pyrimido[4,5-e][1,4]oxazepin-5-ones were prepared directly via the reaction of either ethyl 4-chloro-2-phenyl-5-pyrimidinecarboxylate (Ia) or ethyl 4-chloro-2-m-chlorophenyl-5-pyrimidinecarboxylate (Ib) with a variety of substituted 2-(alkylamino)ethanols. A typical example was the preparation of 8,9-dihydro-9-methyl-2-phenylpyrimido[4,5-e][1,4]-oxazepin-5(7H)-one (IIa) from the reaction of Ia with 2-(methylamino)ethanol. Hydrolytic cleavage of the lactone ring in IIa with sodium hydroxide solution, followed by acidification with hydrochloric acid afforded 4-[(2-hydroxyethyl)methylamino]-2-phenyl-5-pyrimidinecarboxylic acid (IV). Reactions of IIa with concentrated ammonium hydroxide or hydrazine also caused cleavage of the lactone ring, giving the corresponding amide (V) or hydrazide (VI), respectively. Structural assignments were supported by infrared and nuclear magnetic resonance spectra.     

Synthesis and functionalization of 2-hydroxypyrimido[4,5-b][1,4]oxazine

An efficient synthesis of pyrimido[4,5-b][1,4]oxazines is realized using 5-bromouracil. Substitution in the 2-position was performed by palladium-mediated cross-coupling reactions (Suzuki, Stille and carbon-nitrogen bond forming process) and by S_NAr reactions. Microwave-heating is also used for high-speed synthesis.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.     

Synthesis of novel pyrido[2,3-e][1,3]oxazines

The preparation of novel pyrido[2,3-e][1,3]oxazines starting from 3-hydroxy-pyridine-2-carbonitrile, N-aralkoxy-3-hydroxy-pyridine-2-carboxamides and 3-hydroxy-pyridine-2-carboxylic acid hydrazides is described.     

Synthesis and conformational analysis of naphth[1′,2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1′,2′:5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives

A new functional group, the hydroxy group, was inserted into a Betti base by reaction with salicylaldehyde, and the naphthoxazine derivatives thus obtained were converted by ring-closure reactions with formaldehyde, acetaldehyde, propionaldehyde or phosgene to the corresponding naphth[1′2′:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine derivatives. Further, the conformational analysis of these polycyclic compounds by NMR spectroscopy and an accompanying molecular modelling are reported; especially, both quantitative anisotropic ring current effects of the aromatic moieties in these compounds and steric substituent effects were employed to determine the stereochemistry of the naphthoxazinobenzoxazine derivatives.     

Synthesis and reactivity of pyrrolo[3,2-d][1,3]oxazine-2,4-dione. Access to new pyrrolo[3,2-e][1,4]diazepine-2,5-diones

A convenient synthesis of pyrrolo[3,2-d][1,3]oxazine-2,4-dione 4 is described and its reactivity towards various nucleophiles studied. The regioselective ring opening of anhydride 4 or its N-alkylated analog 25 in the presence of alanine or proline afforded, respectively, imidazolidinedione 22 and N-protected pyrrolo[3,2-e][1,4]diazepines 30 and 31 in a one-pot process. In a last part of this study, an alternative route to produce a library of eight non protected pyrrolo[3,2-e][1,4]diazepine-2,5-diones 35a–h is described to overcome the limited reactivity of anhydride 4.     

Synthesis of 2,6-disubstituted pyrido[2,3-b][1,4]oxazines

A new preparative method for pyrido[2,3-b][1,4]oxazines from 6-substituted 3-nitro-2-pyridones is demonstrated. This method consists of two steps: O-alkylation and reductive cyclization. In the former step, the bulkiness of both starting nitropyridones and C2 reagents is found to be essential for avoiding N-alkylation, which undergoes O-alkylation efficiently. The subsequent reductive cyclization affords pyridoxazines with carbon substituents at both the 2- and the 6-positions that have not been available.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Regioselective Synthesis of 2-Substituted [1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones by Heteropolyacids

2-Substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3 were synthesized via regioselective cyclization of 4H-[1,2,4]triazol-3-ylsulfanyl-acrylic acids 2 in the presence of catalytic amounts of heteropolyacids at room temperature in very good yields and rates.     

Convenient selective synthesis of 5,7,8,9-tetrahydro-4H,6H-chromeno[2,3-d][1,3]oxazin-4-ones

A method for the synthesis of 5,7,8,9-tetrahydro-4H,6H-chromeno[2,3-d][1,3]oxazin-4-ones was developed. The method involves acid-catalyzed acylation of substituted ethyl 2-amino-4-aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylates with acetic anhydride.