Porphyrins with exocyclic rings. Part 20: Synthesis and spectroscopic characterization of porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole moieties

Porphyrins with fused 2,1,3-benzoxadiazole and 2,1,3-benzoselenadiazole units were prepared by the ‘3+1’ MacDonald-type methodology. 4-Nitro-2,1,3-benzoxadiazole, 6-chloro-4-nitro-2,1,3-benzoxadiazole and 4-nitro-2,1,3-benzoselenadiazole condensed with isocyanoacetates in the presence of the non-nucleophilic base DBU to give tricyclic pyrrole derivatives in excellent yields. Further cleavage of the ester moieties and decarboxylation afforded α-unsubstituted pyrroles and these were further condensed with 2 equiv of an acetoxymethylpyrrole tert-butyl ester to give crude preparations of tripyrranes. The tert-butyl ester protective groups were cleaved with TFA and following dilution with dichloromethane, ‘3+1’ condensation with a pyrrole dialdehyde, and oxidation with ferric chloride, the heterocyclic ring fused porphyrins were obtained in moderate yields. The yields were lower than expected because of difficulties in preparing required tripyrranes due to the reduced reactivity of the pyrrolic intermediates. The UV-vis spectra of these new porphyrin systems were highly modified showing broadened split Soret bands. In addition, the nickel(II), copper(II) and zinc complexes gave unusual UV-vis spectra with weakened split Soret bands and strong Q-type absorptions above 600 nm. These modified structures show some potential for applications as photosensitizers in photodynamic therapy.     

Gould-Jacobs reaction of 6-amino-2,3-diphenylquinoxaline

Summary Catalytic hydrogenation of 2,3-diphenyl-6-nitroquinoxaline led to the corresponding amine1 which in turn afforded products3a-i on reaction with alkoxymethylene derivatives2a-i. Thermal cyclization of3b and3f yielded substituted pyrazinoquinolones5b and5f, respectively. Optimal conditions for the successful hydrolysis of ester5b were found. The structures of all products were deduced from their IR, UV,¹H, and¹³C NMR spectroscopic data.Dedicated to Prof.F. Sauter on the occasion of his 65th birthday     

Microwave-assisted synthesis of 4-amino-3,5-dihalopyridines

4-Amino-3,5-dihalopyridines have been efficiently prepared via microwave-assisted nucleophilic aromatic substitution of 3,4,5-trihalopyridines using 1-1.1 equiv of primary and secondary amines. The reaction is also applicable to electron rich arylamines.     

Application of 9-ethyl[1,2,5]selenadiazolo[3,4-h]quinolones in the synthesis of tricyclic azoloquinolones

A series of tricyclic azoloquinolones was prepared by a novel approach based on the protection of a benzene-1,2-diamine moiety as 2,1,3-benzoselenadiazole ring. A new reductive deselenation of 9-ethylselenadiazolo[3,4-h]quinolones using zinc powder in acetic acid afforded 7,8-diamino-1-ethylquinolones in high yields. The obtained diaminoquinolones were employed as useful substrates in cyclocondensation reactions leading to azoloquinolone derivatives.     

A new and versatile Ugi/SNAr synthesis of fused 4,5-dihydrotetrazolo[1,5-a]quinoxalines

A combinatorial synthetic route yielding fused tetrazolo[1,5-a]quinoxalines is described. The use of 2-fluorophenylisocyanide in the Ugi-tetrazole reaction (tetrazole-U-4CR) followed by a nucleophilic aromatic substitution (S_NAr) affords the tricylic tetrazolo[1,5-a]quinoxaline moiety in good yields and with high diversity.     

A convenient approach to δ-amino-β-ketoesters by vinylogous Mannich reaction of masked acetoacetates

SiCl₄ is an efficient and selective catalyst for the vinylogous Mannich reaction of linear and cyclic synthetic equivalents of acetoacetate dianion, leading to δ-amino-β-ketoesters in moderate to high yields and complete γ-selectivity; anti-diastereoselectivity was observed by using a γ-methyl-substituted cyclic silyloxydiene.     

Vinylic Substitution of Chlorine in the Reaction of 2,3,5,6-Tetrachloro-1,4-Benzoquinone with Cyclohexylamine in Acetonitrile Solvent

The reaction of 2,3,5,6-tetrachloro-1,4-benzoquinone with cyclohexylamine in acetonitrile has been studied spectrophotometrically. The mechanism of the reaction is a concerted vinylic substitution of Cl atoms. Kinetics and activation parameters are reported. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis and X-ray structures of iodothiacalix[4]arenes

Mono-, di-, and tetraiodothiacalix[4]arenes 13-16 have been successfully synthesized for the first time by the Griess reaction of diazonium salts of the corresponding aminothiacalix[4]arenes 4-7. X-ray crystallography reveals that monoiodinated compound 13 adopts a distorted pinched cone conformation, in which the three hydroxy groups and the iodine atom form a pseudo-cyclic hydrogen bonding. On the other hand, tetraiodinated compound 16 adopts a 1,3-alternate conformation presumably due to the steric hindrance and dipole repulsion between the iodine atoms.     

Synthetic studies on 3-arylquinazolin-4-ones: intramolecular nucleophilic aromatic substitution reaction of 2-carboxamido-3-arylquinazolin-4-ones and its application to the synthesis of secondary aryl amines

The general synthesis and a novel intramolecular nucleophilic aromatic substitution (S_NAr) reaction of 2-carboxamido-3-arylquinazolin-4-ones, a potentially useful scaffold in the field of medicinal chemistry, are described. The synthetic utility of the S_NAr reaction as a tool for the synthesis of secondary aryl amines, including diaryl amines, is also demonstrated.     

Molecular and crystal structures of 5,7-dichloro-4-nitro-2,1,3-benzoxadiazole and products of its reactions with secondary amines

The molecular and crystal structures of 5,7-dichloro-4-nitro-2,1,3-benzoxadiazole and products of its reactions with hexamethyleneimine and dimethylamine were established by X-ray diffraction analysis. The molecular structures and the systems of hydrogen bonds in the crystals of these compounds are discussed.     

Combinatorial synthesis of 4-oxo-4H-imidazo[1,5-a]quinoxalines and 4-oxo-4H-pyrazolo[1,5-a]quinoxalines

A combinatorial synthetic route yielding imidazo[1,5-a]quinoxalines and pyrazolo[1,5-a]quinoxalines is described. The use of 2-fluoroaniline and 1H-imidazole-4-carboxylic acid, respectively, 1H-pyrazole-3-carboxylic acid in the Ugi-reaction (U-4CR) followed by a nucleophilic aromatic substitution (S_NAr) affords the imidazo- as well as the pyrazolo-[1,5-a]quinoxaline moiety in good yield and high diversity.     

Nucleophilic aromatic substitution reaction of nitroarenes with alkyl- or arylthio groups in dimethyl sulfoxide by means of cesium carbonate

Treatment of nitroarenes having electron-withdrawing groups at the ortho or para position with alkanethiol in the presence of cesium carbonate in dimethyl sulfoxide at 25 °C leads to nucleophilic displacement of the nitro group with the alkylthio group. Cesium carbonate is superior to other bases such as potassium carbonate, sodium carbonate, and triethylamine. The cesium-mediated nucleophilic aromatic substitution reaction provides a mild yet powerful and user-friendly protocol for the synthesis of aryl sulfides.     

合成2—芳氧基—5—氟—3H—4—嘧啶酮的新方法

由２－氰－５－氟－３Ｈ－４－嘧啶酮和取代苯酚钠在常压下反应，合成了７个未见文献报道的２－芳氧基－５－氟－３Ｈ－４－嘧啶酮化合物，产率７０￣８７％，结构经ＩＲ、＾１Ｈ ＮＭＲ和ＭＳ证实。     

A vicarious approach to porphyrin aldehydes

The novel synthesis of nitro-porphyrin aldehydes via vicarious nucleophilic substitution of hydrogen in the corresponding nitro-meso-tetraphenylphyrinates (Zn^II, Cu^II) with haloform carbanions, followed by hydrolysis of the introduced dihalomethyl groups under mild conditions (H₂O–toluene, AgClO₄, reflux) is described.     

Double nucleophilic reaction of amines to the imidazole nucleus and selective synthesis of 5-aminoimidazoles

Reaction of 2-(1-chloro-2,2-dimethylpropyl)-1-methyl-1H-imidazole with an excess of N,N-dimethylamine at room temperature gave an abnormal adduct, trans-4,5-bis(dimethylamino)-1-methyl-2,2-dimethylpropyl-2-imidazoline, which was derived from a serial, double nucleophilic addition into the imidazole nucleus in 74% yield together with a normal S_N product, 1-methyl-2-(1-dimethylamino-2,2-dimethylpropyl)-1H-imidazole in 15% yield. The former was easily converted to 1-methyl-5-(dimethylamino)-2-(2,2-dimethylpropyl)-1H-imidazole by only reflux in toluene in 90% yield. The scope, mechanism and limitation of these reactions are discussed.     

Synthesis of substituted 2-amino-4-quinazolinones via ortho-fluorobenzoyl guanidines

A novel route to 12 substituted 2-amino-4-quinazolinones is described. Starting from 2,6-difluoro-4-methoxybenzonitrile, substitution of one of the fluorine atoms either directly or indirectly with heterocycles (e.g., pyridyl, thiazolyl, pyrazolyl) followed by hydrolysis of the nitrile gave a series of o-fluorobenzoic acid derivatives. Condensation with a set of six N,N-disubstituted guanidines followed by base-promoted ring closure afforded 2-amino-4-quinazolinone derivatives.     

Regioselective, nucleophilic carbon-carbon bond formation at the C4-position of indoles initiated by the aromatic Pummerer-type reaction

The treatment of the 5-(phenylsulfinyl)indoles with trifluoroacetic anhydride in the presence of carbon nucleophiles achieved the title reactions with complete regioselectivity.     

Novel approach towards 3,7-disubstituted 1,6-naphthyridin-4(1H)-ones exploiting cross-coupling and SNAr reactions of a dihalogenated compound

A new route towards the synthesis of a series of 3,7-disubstituted 1,6-naphthyridin-4(1H)-ones in moderate to good yields is reported. The strategy involves the preparation of a 3,7-dihalogenated compound that undergoes differential functionalization using palladium-catalyzed cross-coupling and S_NAr reactions.     

A Mitsunobu reaction to functionalized cyclic and bicyclic N-arylamines

The scope of an unexpected Mitsunobu cyclisation to prepare N-arylated Fsp³-enriched azacycles was investigated. In the current study, we have identified whether a pKa-dependent Mitsunobu cyclodehydration or a pKa-independent Mitsunobu intramolecular reaction was in operation. A Mitsunobu reaction, creating a leaving group, followed by intramolecular nucleophilic displacement was determined to be the dominant pathway.     

Efficient palladium-catalyzed C-S cross-coupling reaction of benzo-2,1,3-thiadiazole at C-5-position: A potential class of AChE inhibitors

Functionalization of 2,1,3-benzothiadiazole (BTD) with thiols at C-5 position remains low explored. Moreover, the arylthiol-substitutions at this position are also unexplored and can not be found by a S_N2 or S_N1 reaction. In this sense, herein we present a new palladium-catalyzed methodology for a wide variety of unpublished 5-arylsulfanyl-benzo-2,1,3-thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L-Pro)₂ as low-coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl-benzo-2,1,3-thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors.