Behavior of 6-cyclopropyl- and 6-bromo-7-cyclopropyl-1,4-benzodioxanes under electrophilic substitution reaction conditions

Bromination of 6-cyclopropyl-1,4-benzodioxane occurs with concerted orientation of the ethylenedioxy group and the cyclopropyl radical for the least sterically hindered position of the aromatic ring. Nitration of 6-bromo-7-cyclopropyl-1,4-benzodioxane does not lead to products of substitution of the hydrogen atom in the 5 or 8 position of the 1,4-benzodioxane, but rather to the nitrodebromination product: 7-nitro-6-cyclopropyl-1,4-benzodioxane. The anomalous behavior of the bromo-substituted benzodioxane is explained by the predisposition of the carbon atom bonded to the bromine towardipso attack by an electrophile.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 618–620, May, 1998.     

6-Cyclopropyl- and 6-(1-methylcyclopropyl) 1,4-benzodioxanes: synthesis and nitration. Rearrangement of nitro substituted 6-cyclopropyl-1, 4-benzodioxanes using concentrated sulfuric acid

6-Cyclopropyl- and 6-(1-methylcyclopropyl)-1,4-benzodioxanes have been synthesized as the first cyclopropyl 1,4-benzodioxanes. It was shown that nitration of these compounds occurs with retention of the three carbon ring. In contrast to simple ethers of cyclopropylphenols, nitration leads only to 7-nitro-6-cyclopropyl- and 7-nitro-6-(1-methylcyclopropyl)-1, 4-benzodioxanes,respectively. Nitration of 7-nitro-6-cyclopropyl-1,4-benzodioxane occurs regioselectively to give exclusively the 7 8-dinitro product. The structure of the nitration products was confirmed by their rearrangement to the corresponding nitrosopropionyl-1,4-benzodioxanes.M. V. Lomonosov State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 472–479, April, 1994. Original article submitted February 2, 1994.     

The Synthesis of 1,4‐Bis[N‐(4/6‐Substituted Benzothiazole‐2‐yl)‐N′‐Glycosylguanidino]Benzenes

The starting material O‐protected glycosyl isothiocyanate ( 1?3 ) was refluxed with 1,4‐diaminobenzene in CHCl₃ under nitrogen atmosphere to give 1,4‐bis(N‐glycosyl)thioureidobenzene ( 4?6 ). Then 1,4‐bis[N‐(4/6‐substituted benzothiazole‐2‐yl)‐N′‐glycosylguanidino]benzenes ( 8a?8e , 9a?9e , 10a?10e ) were obtained in good yield by reaction of compounds ( 4?6 ) with 2‐amino‐4/6‐benzothizoles ( 7a?7e ) and HgCl₂ in the presence of TEA in DMF. The structures of all 18 new compounds were confirmed by IR, ¹H NMR, LC‐MS and elemental analysis. The bioactivity of anti‐HIV‐1 protease (HIV‐1 PR) and against angiotensin converting enzyme (ACE) have been evaluated.     

One-step furan ring formation: Synthesis of furo[3,2-h]quinolones

The one-pot reaction of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate ( 6 ) with tert-butyl acetoacetate gave 3-tert-butyl 7-ethyl 9-cyclopropyl-4-fluoro-6,9-dihydro-2-methyl-6-oxofuro[3,2-h]quinoline-3,7-dicarboxylate ( 5 ). This regioselective cyclization was rationalized by the Hard and Soft Acids and Bases principle. By use of a similar furan-forming reaction, we prepared 2-(amino-methyl)furo[3,2-h]quinoline-7-carboxylic acid 4 . Compound 4 showed weak antibacterial activity.     

Crystalline 2π Aromatic Azadiboriridinylium: A BN Analogue of Cyclopropenylium Cation

N-Substitution of a thermally unstable diboratriazole 1 with a trimethylsilyl group affords a remarkably stable diboratriazole derivative 2 . Ring contraction of 2 with an N-heterocyclic carbene accompanied by the release of N₂ as well as 1,4-hydrogen shift affords a carbene-stabilized azadiboriridine 3 . Abstraction of the H−B_3mem hydride in 3 with methyl trifluoromethanesulfonate leads to the isolation of a hitherto unknown azadiboriridinylium 4 , the first BN analogue of cyclopropenylium cation. X-ray diffraction analysis and computational studies confirmed the delocalization of π electrons over the B₂N three-membered ring, indicating the 2π aromatic feature. Compound 4 undergoes ring expansion reactions with azobenzene and pyridazine to furnish triazadiborolidinylium species 5 and 6 , the latter of which possesses a cationic B₂N₃ ring with a pronounced 6π aromatic property. Moreover, the reaction of 4 with a diazo compound produces a cationic B₂N₃C pentafulvene derivative 7 .     

A new synthetic route to 7-halo-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid,an intermediate for the synthesis of quinolone antibacterial agents

Starting from m-fluorotoluene, 7-chloro-6-fluoro- and 6,7-difluoro-1-cyclopropyl-1,4-dihydro-4-oxoquino-line-3-carboxylic acids, 3 and 16 were synthesized. Compounds 3 and 16 are useful intermediates for the synthesis of a class of quinolone antibacterial agents. The synthetic route involves two processes; i) construction of the quinoline ring by an intramolecular cyclization accompanied by the elimination of a nitro group and ii) introduction of fluorine atom by replacement of a nitro group with potassium fluoride. 7-(3-Amino-1-pyrroli-dinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (18) was prepared from 3 or 16. The antibacterial activity of 18 compares favorably with that of ciprofloxacin (2) .     

Racemic isopropyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(6‐methyl‐2‐pyridyl)‐3‐nitropyridine‐5‐carboxylate hemi­benzene solvate

This analysis establishes the rotameric orientation of the pyridyl‐ring N atom of the title compound, C₁₇H₂₁N₃O₄·0.5C₆H₆, as antiperiplanar (ap) to the 1,4‐dihydropyridine H‐4, the absence of an intramolecular hydrogen bond between the 1,4‐dihydropyridine NH and the pyridyl‐N atom, and the unusual planarity of the 1,4‐dihydropyridine ring.     

A Carbon Electrode Functionalized by a Tricopper Cluster Complex: Overcoming Overpotential and Production of Hydrogen Peroxide in the Oxygen Reduction Reaction

A study of the oxygen reduction reaction (ORR) on a screen printed carbon electrode surface mediated by the tricopper cluster complex Cu₃(7‐N‐Etppz(CH₂OH)) dispersed on electrochemically reduced carbon black, where 7‐N‐Etppz(CH₂OH) is the ligand 3,3′‐(6‐(hydroxymethyl)‐1,4‐diazepane‐1,4‐diyl)bis(1‐(4‐ethyl piperazin‐1‐yl)propan‐2‐ol), is described. Onset oxygen reduction potentials of about 0.92 V and about 0.77 V are observed at pH 13 and pH 7 vs. the reversible hydrogen electrode, which are comparable to the best values reported for any synthetic copper complex. Based on half‐wave potentials (E_1/2), the corresponding overpotentials are about 0.42 V and about 0.68 V, respectively. Kinetic studies indicate that the trinuclear copper catalyst can accomplish the 4 e^? reduction of O₂ efficiently and the ORR is accompanied by the production of only small amounts of H₂O₂. The involvement of the copper triad in the O₂ activation process is also verified.     

η6-Arenetricarbonylchromium(0) Complexes in the Synthesis of 1,4-Benzodiazepines and Its Nucleophilic Substituted Products

Abstract

7-Chloro-5-carbomethoxy-1,3-dihydro-2H-1,4-benzodiazepines and its nucleophilic substituted products were synthesized via η⁶-arenetricarbonylchromium(0) intermediates. Ring enlargement of 5-chloro-N-chloroacetylisatin with hexamine in presence of Cr(CO)₆ led to the formation of 7-chloro-5-carbomethoxy-1,3-dihydro-2H-1,4-benzodiazepine in good yield with reduced reaction time. Nucleophilic substitutions on arene ring of η⁶-arenetricarbonylchromium(0) complexes with thiols, phenol, and primary amines were successfully carried out in decalin medium.     

Synthesis of 2-cyclopropyl-4-pyrones and 5-cyclopropyl-2-alkylene-3(2H)-furanones based on tandem cyclization-cyclopropanation strategy

In AgSbF₆/Rh₂(OAc)₄/DCE system, two-component diastereoselective reactions of 2-diazo-3,5-dioxo-6-ynoates (phosphonates and sulphones) and alkenes provided easy access to 2-cyclopropyl-γ-pyrones through 6-endo-dig cyclization-cyclopropanation. In AgOAc/Rh₂(OAc)₄/Et₃N/DCE system, two-component reaction of 2-diazo-3,5-dioxo-7-aryl-6-ynoates and alkenes afforded 2-cyclopropyl-2-alkylene-3(2H)-furanones through 5-exo-dig cyclization-cyclopropanation. The possible mechanism of reaction is discussed. A simple procedure and mild conditions are significant features of this strategy.     

Reaction of N-acetyl- and N-[1-(arylsulfonylimino)ethyl]-1,4-benzoquinone imines with sodium arenesulfinates

N-Acetyl- and N-[1-(arylsulfonylimino)ethyl]-1,4-benzoquinone imines having no substituent in the 2- and/or 6-position of the quinoid ring react with sodium arenesulfinates preferentially according to the 1,4-addition pattern. The presence of an ArSO₂N group favors radical ion reaction with formation of 1,6-addition products.     

1,4-Dihydropyridine derivatives as deactivators of singlet oxygen

The constants of deactivation (k_q) of ¹O₂ by 1,4-dihydropyridine (1,4-DHP) derivatives were determined by quenching of the luminescence of singlet oxygen (¹O₂). The k_q values for 1,4-DHP derivatives range from 10⁶ to 10⁷ litersmole^–1-sec^–1 and depend to a considerable extent on the nature of the substituents in the 1,4-DHP ring. The presence of a substituent in the 4 position decreases k_q, while conversion of the 1,4-DHP system to the corresponding pyridine system deprives the compound of its ability to deactivate ¹O₂. As a result of tests of 12 1,4-DHP derivatives it was found that 2,6-dimethyl-3,5-di (phenylcarbamoyl)-1,4-dihydropyridine deactivates ¹O₂ most effectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 924–926, July, 1981.     

Eight new crystal structures of 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil: insights into the hydrogen‐bonded networks and the predominant conformations of the C5‐bound residues

In order to examine the preferred hydrogen‐bonding pattern of various uracil derivatives, namely 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil, and for a conformational study, crystallization experiments yielded eight different structures: 5‐(hydroxymethyl)uracil, C₅H₆N₂O₃, (I), 5‐carboxyuracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₄·C₃H₇NO, (II), 5‐carboxyuracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₄·C₂H₆OS, (III), 5‐carboxyuracil–N,N‐dimethylacetamide (1/1), C₅H₄N₂O₄·C₄H₉NO, (IV), 5‐carboxy‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₃S·C₃H₇NO, (V), 5‐carboxy‐2‐thiouracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₃S·C₂H₆OS, (VI), 5‐carboxy‐2‐thiouracil–1,4‐dioxane (2/3), 2C₅H₄N₂O₃S·3C₆H₁₂O₃, (VII), and 5‐carboxy‐2‐thiouracil, C₁₀H₈N₄O₆S₂, (VIII). While the six solvated structures, i.e. (II)–(VII), contain intramolecular S(6) O—H…O hydrogen‐bond motifs between the carboxy and carbonyl groups, the usually favoured R₂²(8) pattern between two carboxy groups is formed in the solvent‐free structure, i.e. (VIII). Further R₂²(8) hydrogen‐bond motifs involving either two N—H…O or two N—H…S hydrogen bonds were observed in three crystal structures, namely (I), (IV) and (VIII). In all eight structures, the residue at the ring 5‐position shows a coplanar arrangement with respect to the pyrimidine ring which is in agreement with a search of the Cambridge Structural Database for six‐membered cyclic compounds containing a carboxy group. The search confirmed that coplanarity between the carboxy group and the cyclic residue is strongly favoured.     

A synchrotron radiation study of the one‐dimensional complex of sodium with (1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d‐ribitol,a member of the 'immucillin' family

The sodium salt of [immucillin‐A–CO₂H]⁻ (Imm‐A), namely catena‐poly[[[triaquadisodium(I)](μ‐aqua)[μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol][triaquadisodium(I)][μ‐(1S)‐N‐carboxylato‐1‐(9‐deazaadenin‐9‐yl)‐1,4‐dideoxy‐1,4‐imino‐d ‐ribitol]] tetrahydrate], {[Na₂(C₁₂H₁₃N₄O₆)₂(H₂O)₇]·4H₂O}_n, (I), forms a polymeric chain via Na⁺—O interactions involving the carboxylate and keto O atoms of two independent Imm‐A molecules. Extensive N,O—H...O hydrogen bonding utilizing all water H atoms, including four waters of crystallization, provides crystal packing. The structural definition of this novel compound was made possible through the use of synchrotron radiation utilizing a minute fragment (volume ∼2.4 × 10⁻⁵ mm⁻³) on a beamline optimized for protein data collection. A summary of intra‐ring conformations for immucillin structures indicates considerable flexibility while retaining similar intra‐ring orientations.     

3‐Methyl 5‐isopropyl 2‐methoxy­imino­methyl‐6‐methyl‐4‐(3‐nitro­phenyl)‐1,4‐di­hydro­pyridine‐3,5‐di­carboxyl­ate

The crystal structure of the title compound, C₂₀H₂₃N₃O₇, consists of relatively isolated mol­ecules. The substituted 1,4‐di­hydro­pyridine ring adopts a flattened boat conformation. Both ester groups, at positions 3 and 5, have cis,cis geometry. The phenyl ring is nearly planar and is approximately perpendicular to the 1,4‐di­hydro­pyridine ring (dihedral angle 87.70°).     

Halogen effects in Robinson-Gabriel type reaction of cyclopropanecarboxylic acid N′-substituted-hydrazides with PPh3/CX4

We found that the reaction of cyclopropanecarboxylic acid N′-substituted-hydrazides with PPh₃/CCl₄ proceeded smoothly to give the corresponding normal Robinson-Gabriel type product 2-cyclopropyl-5-substituted-[1,3,4]-oxadiazoles in good yields. Using CBr₄ or CI₄ instead of CCl₄ in the above system, the ring opening of cyclopropane occurred after dehydration to give the corresponding 2-(3-halopropyl)-5-substituted-[1,3,4]-oxadiazoles (4 or 5) in good yields.     

Nitropyrazoles: XII. Transformations of the 4-Methyl Group in 1,4-Dimethyl-3,5-dinitropyrazole and Cyclization of the Transformation Products

A preparative procedure for the synthesis of 1,4-dimethyl-3,5-dinitropyrazole by nitration of 1,4-dimethylpyrazole was developed. The reaction of 1,4-dimethyl-3,5-dinitropyrazole with dimethoxymethyl- (dimethyl)amine (N,N-dimethylformamide dimethyl acetal) gave (E)-N,N-dimethyl-2-(1-methyl-3,5-dinitropyrazol- 4-yl)ethenylamine. Acid hydrolysis of the latter afforded (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde, and the reaction with sodium nitrite in hydrochloric acid led to formation of 2-hydroxymino-2-(1-methyl- 3,5-dinitropyrazol-4-yl)acetaldehyde. The corresponding O-methyloxime and phenylhydrazone reacted with K₂CO₃ to give 6-methyl-4-nitropyrazolo[4,3-d]isoxazole-3-carbaldehyde O-methyloxime and 1-methyl-3-nitro-4-(2-phenyl-2H-1,2,3-triazol-4-yl)pyrazol-5-ol, respectively. Treatment of (1-methyl-3,5-dinitropyrazol-4-yl)-acetaldehyde with benzenediazonium chloride gave (1-methyl-3,5-dinitropyrazol-4-yl)acetaldehyde phenylhydrazone which underwent intramolecular cyclization with replacement of the 5-nitro group by the action of K₂CO₃ in acetonitrile; in the reaction with K₂CO₃ in ethanol, the 5-nitro group was replaced by ethoxy.     

1,4‐Bis{[hydroxy(phenyl)phosphoryl]methyl}piperazine‐1,4‐diium tetrachloridocadmate(II) dihydrate and the cobaltate(II) analogue

The reaction of aminophosphinic acid with CdCl₂·2.5H₂O or CoCl₂·6H₂O in concentrated hydrochloric acid yielded the isostructural compounds 1,4‐bis{[hydroxy(phenyl)phosphoryl]methyl}piperazine‐1,4‐diium tetrachloridocadmate(II) dihydrate, (C₁₈H₂₆N₂O₄P₂)[CdCl₄]·2H₂O, (I), and 1,4‐bis{[hydroxy(phenyl)phosphoryl]methyl}piperazine‐1,4‐diium tetrachloridocobaltate(II) dihydrate, (C₁₈H₂₆N₂O₄P₂)[CoCl₄]·2H₂O, (II). The asymmetric unit of each contains two half dications, both located on crystallographic centres of inversion, a tetrachloridometallate(II) dianion and two solvent water molecules. The residues are linked into two‐dimensional layers in the ab plane by O—H...O hydrogen bonds.     

Reductive Ring‐Opening Reaction of 2,3‐Epoxy‐1,4‐butanediones with SbCl3‐Bu4NI in the Presence of Na2S2O3·5H2O

1,4‐Disubstituted 2,3‐epoxy‐1,4‐butanediones were converted to 1,4‐disubstituted 2‐hydroxy‐1,4‐butanediones with SbCl₃‐Bu₄NI in the presence of Na₂S₂O₃ · 5H₂O. The ring opening of terminal epoxides can also be accomplished to afford the corresponding haloalcohol with SbCl₃ and tetrabutylammonium halides, Bu₄NX (X=Cl, Br, I) under the same reaction conditions.     

Cyclometallated compounds. XV.

The title complex, tetra‐μ‐acetato‐O:O′‐bis{[μ‐1,4‐bis(2‐­pyridyl­oxy)­phenyl­ene‐N,C²:N′,C⁶]dipalladium(II)} bis­(tri­chloro­methane) dihydrate, [Pd₄(C₁₆H₁₀N₂O₂)₂(C₂H₃O₂)₄]·2CHCl₃·2H₂O, the product of the reaction of 1,4‐bis(2‐pyridyl­oxy)­benzene with palladium acetate, is shown to be a tetranuclear, rather than a polymeric, species. It crystallizes about a centre of inversion and has two doubly cyclo­palladated ligands bridged by four acetate groups. The cyclo­palladated ligand is far from planar in the complex and has the central benzene rings π‐stacked. The chelate rings exist in shallow boat conformations.