Pd(PPh3)4-catalyzed direct ortho-fluorination of 2-arylbenzothiazoles with an electrophilic fluoride N-fluorobenzenesulfonimide (NFSI)

An efficient protocol was developed for regio-selective Pd-catalyzed direct ortho-fluorination of 2-arylbenzo[d]thiazoles using N-fluorobenzenesulfonimide (NFSI) as the F⁺ source, and l-proline as the crucial promoter. The present method offered a practical route to synthesize valuable fluorinated products, which are of potential importance in the pharmaceutical and agrochemical industries.     

A facile synthesis of 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones by the reaction of 1,1-dimethylethyl 2-isocyanobenzoates with N,N-dialkyliminium iodides

A convenient synthetic approach to 2-[1-(dialkylamino)alkyl]-4H-3,1-benzoxazin-4-ones has been developed. Thus, 1,1-dimethylethyl 2-isocyanobenzoates, which can be readily prepared from 2-nitrobenzoic acids by a simple four-step sequence, react with N,N-dialkyliminium iodides without using any catalysts under mild conditions to give the desired products in generally fair-to-good yields.     

Base promoted facile route to functionalized benzo[b][1,8]naphthyridin-2-(1H)-ones from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides

A facile synthesis of 4-amino-N-benzylbenzo[b][1,8]naphthyridin-2(1H)-ones 3 is described from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides 2 with t-BuOK in excellent yields in mild conditions. These reactions proceeded at room temperature under aerobic atmosphere in very short period. The cyclization reactions were also extended with N-alkyl amino acetamide analogues affording the products in good yields.     

A one-pot synthesis and mild cleavage of 2-[2- or 5-(alkylsulfanyl)pyrrol-1-yl]ethyl vinyl ethers by t-BuOK/DMSO: a novel and facile approach to N-vinylpyrroles

Substituted N-[2-(vinyloxy)ethyl]pyrroles, prepared in good yield through an allenic or acetylenic carbanion/isothiocyanate one-pot methodology from 2-(vinyloxy)ethyl isothiocyanate and allyloxyallene, methoxyallene, N,N-dimethyl-2-propyn-1-amine, and 3-methoxy-1-(methylsulfanyl)-1-propyne, are smoothly converted into the corresponding N-vinylpyrroles using t-BuOK/DMSO (room temperature). The reaction proceeds via elimination of vinyl alcohol from the N-[2-(vinyloxy)ethyl] substituent and represents a novel approach to N-vinylpyrroles.     

An efficient synthesis of furyl sulfonamides from the reaction of furan with in situ generated N-tosyl imines

Treatment of an aldehyde and furan with N-sulfinyl-p-toluenesulfonamide/zinc chloride leads to the formation of furyl sulfonamides via an in situ generated N-tosyl imine intermediate. In one case, a novel 4-tosylamino-5,6-dihydro-4H-3-oxa-benz[e]azulene was obtained by intramolecular aromatic substitution of the activated imine at the 3-position of the furan ring.     

Syntheses and evaluation of fluorinated benzothiazole anilines as potential tracers for β-amyloid plaques in Alzheimer's disease

[¹¹C]2-(4′-(Methylamino)phenyl)-6-hydroxybenzothiazole ([¹¹C]PIB) is a most potential PET tracer for detecting the β-amyloid plaques in Alzheimer's disease. Here the syntheses of three fluorinated PIB, namely 2-(4′-(methylamino)phenyl)-6-fluoroethoxybenzothiazole (O-FEt-PIB), 2-(4′-(methylamino)phenyl)-6-fluoro-benzothiazole (F-N-Me) and 2-(4′-(dimethylamino)phenyl)-6-fluorobenzo-thiazole (F-N,N-Me), and the radiosynthesis of one corresponding ¹⁸F-labeled PIB compound, [¹⁸F]O-FEt-PIB, as well as their in vitro/in vivo biological characters were reported. The structures of the products were confirmed by IR, ¹H NMR, EI/ESI-MS, elemental analysis and HRMS techniques. The radiolabeled product was characterized by radio-TLC and radio-HPLC and purified by semi-preparative radio-HPLC. The suitable biological characters showed these tracers were potential to be developed as probes for detecting β-amyloid plaques in Alzheimer's disease.     

Investigation towards an efficient synthesis of benzo[g]isoquinoline-1,5,10(2H)-triones

As part of our research on 2-aza analogues of pentalongin, the active principle of Pentas longiflora Oliv., the first synthesis of 2,3-disubstituted benzo[g]isoquinoline-1,5,10(2H)-triones via 3,4-disubstituted 6-hydroxybenzo[g]furo[4,3,2-de]isoquinoline-2,5(4H)-diones as the key intermediates is reported. The latter compounds have been prepared by treating 2-methoxycarbonyl-1,4-naphthoquinone with N-substituted enaminoesters under acidic conditions. These reagents are easily accessible from readily available 1,4-dihydroxy-2-naphthoic acid, β-ketoesters and primary amines. Finally, a short synthesis of substituted benzo[g]isoquinoline-1,5,10(2H)-triones is achieved by an oxidative addition of N-substituted enaminoesters onto methyl 1,4-dihydroxynaphthalene-2-carboxylate.     

First straightforward synthesis of 2,4-disubstituted benz[g]isoquinoline-3,5,10(2H)-triones, 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones

Structural modifications to the benz[g]isoquinoline skeleton of N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were envisaged in order to make future SAR studies possible for this type of bioactive compounds. Several N-substituted benz[g]isoquinoline-3,5,10(2H)-triones were converted to novel 2,4-substituted benz[g]isoquinoline-3,5,10(2H)-triones, new tetracyclic 1,2,3,5-substituted naphtho[3,2,1-de]isoquinoline-4,7-diones, and 6-substituted benzo[h]pyrido[3,4,5-kl]-1,2,3,4-tetrahydroacridine-5,8-diones. All the synthesized target compounds represent new heterocyclic systems, which were previously undescribed in the literature.     

Synthesis of a novel tetracyclic azaindolo[2,1-c][1,4]benzoxazine ring system

Synthesis of a series of novel fused tetracyclic mono- and diazaindolo[2,1-c][1,4]benzoxazine heterocyclic compounds 3a-o has been achieved in a two-step one-pot reaction set up starting from commercially available or easily accessible inputs. For example, reaction of di-lithiated (N-Boc)-2-amino-3-methylpyridine Li₂-2a with Weinreb amide of 2-(2,4-difluorophenoxy)-2,2-dimethylacetic acid 1a, followed by TFA treatment furnished the tetracyclic compound 3a, which is essentially a fusion of 7-azaindole and 3,4-dihydro[1,4]benzoxazine, in 70% isolated yield. A competitive elimination by-product 4a was also observed (24% isolated yield) in this case. Based on our initial results, a structural basis and molecular mechanism have been suggested to explain these two parallel reactions. Consequently, with appropriate structural tuning of 1, formation of the individual products can be controlled.     

N-Polyfluoroethyl and N-2-chlorodifluorovinyl derivatives of azoles

Reactions of tetrafluoroethylene, chlorotrifluoroethylene and 1,2-dichlorodifluoroethylene with N-potassium salts of imidazole, 2-methylbenzimidazole, 3,5-dimethylpyrazole, 1,2,4-triazole, and benzotriazole lead to the formation of the corresponding N-(1,1,2,2-tetrafluoroethyl), N-(2-chloro-1,1,2-trifluoroethyl), and N-(2-chloro-1,2-difluorovinyl) azoles. Treatment of N-(2-chloro-1,2-difluorovinyl) and N-(2-chloro-1,1,2-trifluoroethyl) derivatives of azoles with tetramethylammonium fluoride is a useful synthetic method for the preparation of heterocycles with 1,2,2,2-tetrafluoroethyl group attached to nitrogen.     

l-Proline-catalyzed three-component domino reactions for the synthesis of highly functionalized pyrazolo[3,4-b]pyridines

A series of novel N,3-dimethyl-5-nitro-1-aryl-1H-pyrazolo[3,4-b]pyridin-6-amines was obtained in good yields from the domino reactions of N-methyl-1-(methylthio)-2-nitroprop-1-en-1-amine, aromatic aldehydes, and 3-methyl-1-aryl-1H-pyrazol-5-amines in ethanol in the presence of green catalyst, l-proline. This transformation involves the formation of two C–C and one C–N bonds leading to the creation of a six-membered ring in a one-pot operation.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

A novel three-component reaction of N-fluoropyridinium salts: a facile approach to imidazo[1,2-a]pyridines

The reaction of N-fluoropyridinium triflate with isonitriles in acetonitrile and propionitrile in the presence of NaBH(OAc)₃ led to the formation of the corresponding imidazo[1,2-a]pyridines in 44-73% yields. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species and apparent reduction of the pyridinium intermediate with NaBH(OAc)₃ to yield the targeted heterocycles.     

Gas-phase pyrolysis of benzimidazole derivatives: novel route to condensed heterocycles

Gas-phase pyrolysis of N-(1H-benzimidazol-2-yl)-N′-arylidenehydrazines 1a-e gave the corresponding arylnitriles 2a-e, 2-aminobenzimidazole 3, 2,4,5-triphenylimidazole 4, 1,3-diphenyl-8H-2,3a,8-triazacyclopenta[a]indene 5, and 5,11-diphenyl-6H,12H-dibenzimidazo[1,2-a];1’,2’-d]pyrazine 6. The kinetics and analysis of the products of reaction are reported and used to elucidate the mechanism of the elimination process.     

Microwave-assisted synthesis of novel N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides inspired by marine topsentines and nortopsentines

We report the synthesis of novel N-(4-phenylthiazol-2-yl)-substituted benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides, which were inspired by marine topsentines and nortopsentines. Condensation of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) with various ortho-halogenated anilines, aminopyridines and aminophenols gave the corresponding aryliminodithiazoles in good to excellent yields. Copper(I)-mediated or nucleophilic-assisted cyclization of aryliminodithiazoles furnished cyano-functionalized benzo[d]thiazoles, thiazolo[4,5-b]- and thiazolo[5,4-b]-pyridines and benzo[d]oxazoles. The latter were condensed with substituted 4-phenylthiazol-2-amines to furnish twenty seven new polyaromatic carboximidamides in moderate to good yields.     

Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine

The reaction of N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine (1) with Fe₂(CO)₉ in refluxing acetonitrile yielded di-(μ₃-thia)nonacarbonyltriiron (2), μ-[N-(5-methyl-2-thienylmethyl)-η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido]hexacarbonyldiiron (3), and N-(5-methyl-2-thienylmethylidene)amine (4). If the reaction was carried out at 45 °C, di-μ-[N-(5-methyl-2-thienylmethylidene)-η¹(N);η¹(S)-2-thiolethylamino]-μ-carbonyl-tetracarbonyldiiron (5) and trace amount of 4 were obtained. Stirring 5 in refluxing acetonitrile led to the thermal decomposition of 5, and ligand 1 was recovered quantitatively. However, in the presence of excess amount of Fe₂(CO)₉ in refluxing acetonitrile, complex 5 was converted into 2-4. On the other hand, the reaction of N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine (6) with Fe₂(CO)₉ in refluxing acetonitrile produced 2, μ-[N-(6-methyl-2-pyridylmethyl)-η¹ (N_py);η¹:η¹(N); η¹:η¹(S)-2-thiolatoethylamido]pentacarbonyldiiron (7), and μ-[N-(6-methyl-2-pyridylmethylidene)-η²(C,N);η¹:η¹(S)-2- thiolethylamino]hexacarbonyldiiron (8). Reactions of both complex 7 and 8 with NOBF₄ gave μ-[(6-methyl-2-pyridylmethyl)-η¹(N_py);η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido](acetonitrile)tricarbonylnitrosyldiiron (9). These reaction products were well characterized spectrally. The molecular structures of complexes 3, 7-9 have been determined by means of X-ray diffraction. Intramolecular 1,5-hydrogen shift from the thiol to the methine carbon was observed in complexes 3, 7, and 9.     

Synthesis and photovoltaic properties of new [1,2,5]thiadiazolo[3,4-c]pyridine-based organic Broadly absorbing sensitizers for dye-sensitized solar cells

In this paper, by introducing [1,2,5]thiadiazolo[3,4-c]pyridine (PT) as an auxiliary acceptor into the molecular design of organic sensitizers, we have synthesized four new dyes (PT1–PT4) for dye-sensitized solar cells (DSSCs) with triphenylamine or N,N-diphenylthiophen-2-amine as the donor units and thiophene or benzene as the π-bridges, respectively. All the structures, optical and electrochemical properties were fully characterized. Nanocrystalline TiO₂ dye-sensitized solar cells were also fabricated using these dyes. Among them, PT2-based DSSCs showed the highest overall conversion efficiency of 6.11% with V_oc=668 mV, J_sc=12.61 mA cm⁻² and a fill factor (FF)=0.74 after a chenodeoxycholic acid (CDCA) treatment under standard illumination condition (100 mW cm⁻² simulated AM 1.5 solar light).     

The first quaternary lanthanide(III) nitride iodides: NaM4N2I7 (M=La-Nd)

In attempts to synthesize lanthanide(III) nitride iodides with the formula M₂NI₃ (M=La-Nd), moisture-sensitive single crystals of the first quaternary sodium lanthanide(III) nitride iodides NaM₄N₂I₇ (orthorhombic, Pna2₁; Z=4; a=1391-1401, b=1086-1094, c=1186-1211 pm) could be obtained. The dominating structural features are chains of trans-edge linked [NM₄]⁹⁺ tetrahedra, which run parallel to the polar 2₁-axis [001]. Between the chains, direct bonding via special iodide anions generates cages, in which isolated [NaI₆]^5- octahedra are embedded. The IR spectrum of NaLa₄N₂I₇ recorded from 100 to 1000 cm^-1 shows main bands at υ=337, 373 and 489 cm^-1. With decreasing radii of the lanthanide trications these bands, which can be assigned as an influence of the vibrations of the condensed [NM₄]⁹⁺ tetrahedra, are shifted toward higher frequencies for the NaM₄N₂I₇ series (M=La-Nd), following the lanthanide contraction.     

Functionalization of aminocrown ethers with [2H]-chromene units by Buchwald-Hartwig C-N coupling for constructing of photoswitchable molecular devices

Functionalization of the diaminodibenzocrown ethers with 2H-[1]benzopyrane and 3H-naphtho[2,1-b]pyrane units by Buchwald-Hartwig C-N coupling was developed. It is demonstrated that the novel molecule possesses photochromic properties that can be modified by the complex formation process.     

Synthesis of N-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

The synthesis of 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-dione hydrochlorides is reported starting from 1,4-dihydrobenz[g]isoquinoline-3(2H)-ones or ethyl (3-aminomethyl-1,4-dimethoxynaphth-2-yl)acetates. A third strategy relies on the synthesis of the title compounds via an N-protected 2-(3-bromomethyl-1,4-dimethoxynaphth-2-yl)ethylamine. The synthesized 1,2,3,4-tetrahydro-benz[g]isoquinoline-5,10-diones are a new class of quinones, which have not been reported yet.