Reaction of [60]fullerene with free radicals generated from active methylene compounds by manganese(III) acetate dihydrate

The reaction of [60]fullerene with dimethyl malonate and diethyl malonate in the presence of manganese(III) acetate dihydrate (Mn(OAc)3.2H2O) for 20 min afforded singly bonded [60]fullerene dimers 1a and 1b in a 1,4-addition pattern. When the reaction time was extended to 1 h, 1,4-bisadducts 2a and 2b were obtained. Unsymmetrical 1,4-adduct 5 and C2 symmetrical 1,16-bisadduct 6 were obtained when diethyl bromomalonate was used as the active methylene compound. Reaction of [60]fullerene with malononitrile and ethyl cyanoacetate with the aid of Mn(OAc)3.2H2O produced methanofullerenes 7 and 8. It is proposed that all these products were formed the addition of free radicals from the active methylene compounds generated by Mn(OAc)3.2H2O.     

Synthesis of two pentaarylated [60]fullerene derivatives Ar_5C_(60)-H (Ar = p-MeC_6H_4, m-MeC_6H_4) and their novel electrochemical properties

Through one pot reaction of C60 with organocopper/magne-sium reagent ( p - MeQ H4 )2 CuMgBr or ( m - MeC6 H )2 -CuMgBr prepared from CuBr-Me2S and p-MeC6H4MgBr or m-MeC6H4MgBr and subsequent quenching with aqueous NH4Cl, two pentaarylated [60] fullerene derivatives (p-MeC6H4)5C60H (1) and (m-MeC6H4)5C60H (2) have been synthesized in 94% and 96% yields, respectively. While known compound 1 prepared via this improved method is unambiguously identified, new compound 2 is fully characterized by elemental analysis, IR, UV-vis, 1H NMR and 13C NMR spectroscopies. Additionally, electrochemical study shows that the two [60] fullerene derivatives 1 and 2 in dichloromethane solution display two sequential one-electron reductions which are shifted by about 0.4V towards more negative potential values with respect to free C60. Such remarkable cathodic shift is attributed to the multiple breakage of the double-bond conjugation within the fullerene core.     

Manganese(III) acetate-mediated free radical reactions of [60]fullerene with beta-dicarbonyl compounds

[60]Fullerene reacted with various beta-dicarbonyl compounds in the presence of Mn(OAc)3*2H2O to generate dihydrofuran-fused [60]fullerene derivatives or 1,4-bisadducts. Dihydrofuran-fused [60]fullerene derivatives 2 could be formed by treatment of alpha-unsubstituted beta-diketones 1a-e or beta-ketoesters 1f and 1g with [60]fullerene in refluxing chlorobenzene in the presence of Mn(III). Solvent-participated unsymmetrical 1,4-bisadducts 3 were obtained through the reaction of [60]fullerene with dimethyl malonate 1h or alpha-substituted beta-dicarbonyl compounds 1i-1n in toluene. A possible reaction mechanism for the formation of different fullerene derivatives is proposed.     

Vinyl Ethers Containing an Epoxy Group: XXII. Synthesis and Base-Catalyzed Transformations of 1-(Allyloxy)- and 1-[2-(Vinyloxy)ethoxy]-3-(2-propynyloxy)propan-2-ols

Reactions of 2-(allyloxymethyl)- and 2-[2-(vinyloxy)ethoxy]methyloxiranes with 2-propynol (～3 wt % of t-BuOK, 75–85°C, 5–10 h) lead to formation of new 1-organyloxy-3-(2-propynyloxy)propan-2-ols (yield 65–95%). On heating to 45–100°C in the presence of bases (KOH, t-BuOK), 1-allyloxy- and 1-[2-(vinyloxy)ethoxy]-3-(2-propynyloxy)propan-2-ols are transformed into the corresponding 2-vinyl-1,3-dioxolane, 6-methyl-2,3-dihydro-1,4-dioxine, 6-methylene-1,4-dioxane, and 2,3-dihydro-5H-1,4-dioxepine derivatives, whose yield and ratio strongly depend on the solvent nature, catalyst, and substituent at the hydroxy group. 2-Vinyl-1,3-dioxolane and 6-methyl-2,3-dihydro-1,4-dioxine derivatives are formed as the major products (yield 70–99%) in the presence of t-BuOK in aprotic media (toluene, THF, DMSO) or in the absence of a solvent as a result of prototropic isomerization followed by intramolecular heterocyclization. Intramolecular nucleophilic cyclization of 3-(2-propynyloxy)propan-2-ols to 6-methylene-1,4-dioxane is the predominant process in water in the presence of KOH. In all cases, the fraction of 2,3-dihydro-5H-1,4-dioxepine derivatives among the cyclization products ranges from 0 to 5% (KOH) or to 14% (t-BuOK).     

Two Stage Solid Phase Extraction with Subsequent HPLC Isolation for Structure Elucidation of Major Metabolites of (+)-(R)-2-{3-(benzo[1,4]dioxan-2-yl-methylamino)-1-propyl}-3(2H)-pyridazinone (GYKI-16084)

GYKI-16084 – (+)-(R)-2-{3-(benzo[1,4]dioxan-2-yl-methylamino)-1-propyl}-3(2H)-pyridazinone hydrochloride – is a new drug candidate for the treatment of benign prostatic hyperplasia. In our study the major metabolites formed in the rat and dog were isolated from dog and rat urine, then their structures were elucidated by means of MS and NMR. A two stage solid phase extraction (SPE) procedure and a semi-preparative HPLC method were developed utilizing various mechanisms of separation. The major metabolites proved to be isomeric glucuronides of the benzodioxane moiety hydroxylated at positions 6 or 7 and {2-(2-carboxyethyl)-3(2H)-pyridazinone}.     

Regioselective synthesis of 1,4-di(organo)[60]fullerenes through DMF-assisted monoaddition of silylmethyl Grignard reagents and subsequent alkylation reaction

Monoaddition of Grignard reagents, in particular tri(organo)silylmethylmagnesium chlorides, to [60]fullerene took place smoothly in the presence of dimethylformamide to produce (organo)(hydro)[60]fullerenes, C60R(1)H, in good yield (up to 93% isolated yield). The hydrofullerene was then deprotonated to generate the corresponding anion, C60R(-), which was then alkylated to obtain 58pi-electron di(organo)[60]fullerenes, C60R(1)R(2), in good to high yield (up to 93% overall yield). The two-step methodology provides a wide variety of 1,4-di(organo)[60] fullerenes bearing the same or different organic addends on the [60] fullerene core. By changing the addends, one can control the chemical and physical properties of the compounds at the molecular and bulk levels.     

Singlet-Oxygen Ene Reactions of (E)-4-Propyl[1,1,-2H3]oct-4-ene. Short Communication

Rose bengal-sensitized photooxygenation of 4-propyl-4-octene ( 1 ) in MeOH/Me₂CHOH 1:1 (v/v) and MeOH/H₂O 95:5 followed by reduction gave (E)-4-propyl-5-octen-4-ol ( 4 ), its (Z)-isomer 5 , (E)-5-propyl-5-octen-4-ol ( 6 ), and its (Z)-isomer 7 . Analogously, (E)-4-propyl[1,1,1-²H₃]oct-4-ene ( 2 ) gave (E)-4-propyl[1,1,1-²H₃]oct-5-en-4-ol ( 14 ), its (Z)-isomer 15 , (E)-5-[3′,3′,3′-²H₃]propyl-5-octen-4-ol ( 16 ), its (Z)-isomer 17 , and the corresponding [8,8,8-²H₃]-isomers 18 and 19 (see Scheme 1). The proportions of 4–7 were carefully determined by GC between 10% and 85% conversion of 1 and were constant within this range. The labeled substrate 2 was photooxygenated in two high-conversion experiments, and after reduction, the ratios 16/18 and 17/19 were determined by NMR. Isotope effects in 2 were neglected and the proportions of corresponding products from 1 and 2 assumed to be similar (% 4 ≈? % 14 ; % 5 ≈? % 15 ; % 6 ≈? % ( 16 + 18 ): % 7 ≈? % ( 17 + 19 )). Combination of these proportions with the ratios 16/18 and 17/19 led to an estimate of the proportions of hydroperoxides formed from 2 . Accordingly, singlet oxygen ene additions at the disubstituted side of 2 are preferred (ca. 90%). The previously studied trisubstituted olefins 20–25 exhibited the same preference, but had both CH₃ and higher alkyl substituents on the double bond. In these substrates, CH₃ groups syn to the lone alkyl or CH₃ group appear to be more reactive than CH₂ groups at that site beyond a statistical bias.     

Intracellular uptake and phototoxicity of 3(1),3(2)-didehydrophytochlorin-fullerene hexaadducts

C(60)-fullerene derivatives are potential building blocks in modular carrier systems for selective tumor targeting. In [5:1] fullerene hexakis adducts, one position can be occupied by an addressing unit (e.g. monoclonal antibody) while the other five positions are suitable for dendrimers or spacers loaded with several drug moieties. This article reports intracellular uptake and phototoxicity of three fullerene hexakis adducts coupled with a different number of photosensitizers: a bis(3(1),3(2)-didehydrophytochlorin)-fullerene [5:1]-hexaadduct (FHP1), a fullerene [5:1]-hexaadduct with six 3(1),3(2)-didehydrophytochlorin groups (FHP6) and a fullerene [6:0]-hexaadduct that carries 12 3(1),3(2)-didehydrophytochlorin units (FHP12). The most promising complex, the hexa-3(1),3(2)-didehydrophytochlorin fullerene hexaadduct FHP6, was also compared with its fullerene-free analogous derivative P6. It was found that the extent of intracellular uptake is influenced by both nanomolecular size and asymmetry (amphiphilicity) of the fullerene complexes. The degree and mechanism of phototoxicity was found to depend on intracellular concentrations and singlet oxygen quantum yields.     

Face-to-face C6F5-[60]fullerene interaction for ordering fullerene molecules and application to thin-film organic photovoltaics

Treatment of [60]fullerene with potassium methylnaphthalenide and excess C(6)F(5)CH(2)Br afforded 1,4-bis(pentafluorobenzyl)[60]fullerene, the study of which showed that there is a face-to-face interaction between [60]fullerene and a perfluoro aromatic ring, allowing the molecule to be utilized for high-performance organic photovoltaic devices.     

Radiolabeling of 1-[N',N'-bis(2-chloroethyl)-4-aminophenyl]-N-methyl-fullereno-C60-[1,9-c]pyrrolidine with 125I

Summary A procedure for labeling of a fullerene derivative 1-[N',N'-bis(2-chloroethyl)-4-aminophenyl]-N-methyl-fullereno-C₆₀-[1,9-c]pyrrolidine (C₆₀-C₁₃H₁₈N₂Cl₂) with ¹²⁵I is reported. The compound was first iodinated with a large excess of iodine monochloride and then radiolabeled by isotopic exchange with Na¹²⁵I in a toluene-water two-phase system. The dependence of the radiolabeling yield on the reaction temperature and exchange time was examined. The radiolabeling yield of the compound was as high as 94% after heating for 2 hours at 130 °C.     

Cooperative C(60) binding to a porphyrin tetramer arranged around a p-terphenyl axis in 1:2 host-guest stoichiometry

[structure: see text] Porphyrin tetramer 1 was newly designed and synthesized to construct a novel cooperative [60]fullerene (C(60)) binding system. Compound 1 has a p-terphenyl axis, which is expected to act as a scaffold for a guest-binding information transducer. In toluene, 1 can bind 2 equiv of C(60) to produce a 1:2 1/C(60) complex with association constants of 5800 M(-1) (K(1)) and 2000 M(-1) (K(2)). These values are significantly greater than those for control porphyrin dimers such as 2 and 3.     

加成产物HC60[CH2C(CH3)=CH2]的电子结构和UV谱

用INDO方法研究C60与2-甲基烯丙基氯化镁的加成产物HC60[CH2C(CH3)=CH2]的两种异构体的结构和UV谱, 表明1,2-加成产物具有Cs对称性, 1,4-加成产物具有C1对称性, 且前者比后者总能量低, 因而更易于形成。产物中2-甲基烯丙基与C60之间靠极性共价键连接, 并发生前者向后者的电子转移。以此优化构型为基础, 计算两种产物异构体的UV谱, 与实验值一致。同时对电子跃迁进行理论指认, 讨论了产物UV谱带红移的原因。     

Tris(eta4-naphthalene)- and tris(1-4-eta4-anthracene)tantalate(1-): first homoleptic arene complexes of anionic tantalum

Reduction of tantalum pentachloride by 6 equiv of sodium naphthalene in 1,2-dimethoxyethane provided, after recrystallization from tetrahydrofuran, 50-55% yields of yellow, pyrophoric [Na(THF)][Ta(C10H8)3]. The product was shown by 1H and 13C NMR spectra and an X-ray study (on the corresponding [Na(crypt 2.2.2)]salt) to be tris(eta4-naphthalene)tantalate(1-), 1, the first homoleptic naphthalene complex of a third row (5d) transition metal. Salts of 1 react under mild conditions with excess CO (1 atm pressure, -60 degrees to +20 degrees C) and 3 equiv of anthracene, C14H10 (20 degrees C), to give 99 and 52% yields of yellow [Ta(CO)6]- and orange [Ta(C14H10)3]-, (2), respectively. The latter is the first homoleptic anthracene complex of a group 5 element and only the third one known, the others being Cr(eta6-C14H10)2 and [Co(eta4-C14H10)2]-. NMR spectra and X-ray structural characterization, as the [Na(crypt 2.2.2)] salt, established 2 to be [Ta(1-4-eta4-C14H10)3]- and is very similar to 1 in solution and in the solid state. Salts of 2 also undergo facile ligand substitution reactions. For example, it reacts with 1,3,5,7-cyclooctatetraene, COT, at 20 degrees in THF to give high yields of the previously known [Ta(COT)3]-, which was structurally characterized as the Na(crypt 2.2.2)salt. One particularly important feature concerning 1 and 2 is that they are the first available synthons for "naked" atomic Ta- and promise to be useful reagents for the general exploration of low-valent tantalum chemistry. Also, 1 and 2 represent the first homoleptic arene tantalum complexes to have been prepared by conventional syntheses. The only previously known substance of this class is the neutral bis(benzene)tantalum(0), which was accessed by the co-condensation of atomic tantalum and benzene vapor in a sophisticated (electron-gun furnace equipped) metal atom reactor.     

Synthesis, electrochemical properties, and thermal transformations of 1-(5-nitropyrimidin-2-yl)[60]fullereno[1,2-b]aziridine

The reaction of fullerene C₆₀ with 2-azido-5-nitropyrimidine afforded 1-(5-nitropyrimidin-2-yl)[60]fullereno[1,2-b]aziridine, whose electrochemical reduction proceeds more easily than the reduction of nonmodified C₆₀. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 484–488, March, 2006.     

Lewis acid-assisted nucleophilic substitution of fullerene epoxide

[Structure: see text] A 1,4-bis(phenyl)-1,4-dihydro[60]fullerene resulting from an efficient nucleophilic substitution has been obtained by reaction of a fullerene epoxide, C60O, with nucleophilic aromatic compounds in the presence of boron trifluoride etherate as a Lewis acid.     

Synthesis of Ethyl (2RS,3SR)-1-Tosyl-3-Vinylazetidine-2-carboxylate and ethyl (2RS,E)-3-ethylidene-1-tosylazetidine-2-carboxylate (=rac-ethyl N-tosylpolyximate)

The synthesis of 3-ethylideneazetidine-2-carboxylic acid (=polyoximic acid; 3 ) is a approached in two different ways leading to potential precursors of 3 . The first way involved a ring closure to a vinyl-subsatituted azetidin. Thus, Ireland-Claisen rearrangement of the Boc-glycinates 6 and 10 of (Z)- and (E)-2-butene-1,4-diol afforded, after exchange of the N-protecting groups, the isomeric 2-(tosylamino)-3-vinylbutanolides 13 and 14 with high stereoselectivity. Only the cis-isomer 14 could be further transformed to 3-(bromomethyl)-2-(tosylamino)-4-pentenoate 17 , and in a smoth cyclization with K₂CO₃, to trans-3-vinylazetidtene-2-carboxylaze 18 (Scheme 2). In the second approach, the 3-ethylidene isomer 19 of 18 was obtained more directly by a [2+2] cycloaddition, together with the two isomers 23 and 24 , from methlallene 20 and (tosyliminno)acetate 21 (Scheme 3). The main product of this reaction was, however, 2-(tosylamino)-4-hexinoate 22 , the product of an ene reaction.     

Synthesis and reactions of 1-[1-oxido-2-(3,4)-pyridinyl]-2-methyloxiranes with nitrogen nucleophiles

Reaction of 2(3,4)-pyridinecarboxaldehydes (5) with ethylidenetriphenylphosphorane afford a mixture of stereoisomers Z-( 6 ) and E-1-[2(3,4)-pyridinyl]-1-propenes ( 7 ). m-Chloroperbenzoic acid oxidation of 6 and 7 yields a 60:40 mixture of Z-( 8 ) and E-1-[1-oxido-2(3,4)-pyridinyl]-2-methyloxiranes ( 9 ). The regiospecific reaction of Z-isomers 8a-c with cyclic amines as piperidine give rise to threo-1-hydroxy-1-[1-oxido-2(3,4)-pyridinyl]-2-(1-piperidino)propanes ( 10 ) while the E-isomer 9a yields erythro- 11 . On tho other hand, the E-isomers 9b and 9c having 1-oxido-3(4)-pyridinyl substituents afford erythro- 12 resulting from attack by piperidine at C-1 of the oxirane. Reductive deoxygenation using 10% palladium on charcoal and hydrogen gas effectively removed the N-oxide substituent from the threo- 10 and erythro- 11 β-aminoalcohols. Dilute solution ir spectroscopy indicated the existance of strong intramolecular hydrogen bonding in the β-aminoalcohols 10 and 11 . The assignment of relative configuration of diastereoisomers 10 and 11 was based on the magnitude of the vicinal coupling constant J where J threo is greater than J erythro.     

Functional polymers. XVI. Synthesis and polymerization of 2(2-hydroxy-5-isopropenylphenyl)-2H-benzotriazole and a new synthesis of 2(2-hydroxy-5-vinylphenyl)2H-benzotriazole

2(2-Hydroxy-5-isopropenylphenyl)2H-benzotriazole was synthesized in 40% overall yield starting from o-nitroaniline. Diazotization in aqueous hydrochloric acid gave o-nitrophenyl diazonium chloride which was condensed with p-hydroxyacetophenone; the azo compound was reduced to 2(2-hydroxy-5-acetylphenyl) 2H-benzotriazole with zinc powder in sodium hydroxide solution and the 2-hydroxy group of the compound was acetylated. Treatment of the acetyl compound with methyl Grignard reagent resulted in the methylation of the 5-acetyl group to 2[2-acetoxy-5(2-hydroxy-2-propyl)phenyl]2H-benzotriazole which was then dehydrated with potassium hydrogen sulfate to the desired 2(2-hydroxy-5-isopropenylphenyl)2H-benzotriazole. This monomer did not homopolymerize, but was copolymerized readily with styrene, methyl methacrylate, and n-butyl acrylate with azobisisobutyronitrile as the initiator. 2(2-Acetoxy-5-acetylphenyl)2H-benzotriazole was also reduced with sodium borohydride to form 2[2-acetoxy-5-(1-hydroxyethyl)phenyl]2H-benzotriazole which was dehydrated and hydrolyzed to the known 2(2-hydroxy-5-vinylphenyl)-2H-benzotriazole. This route provides a novel and simpler synthesis of 2(2-hydroxy-5-vinylphenyl)2H-benzotriazole.     

The reaction of fullerene C(60) with phthalazine: the mechanochemical solid-state reaction yielding a new C(60) dimer versus the liquid-phase reaction affording an open-cage fullerene.

The reaction of fullerene C(60) with phthalazine was studied both in solution and in the solid state using the high-speed vibration-milling technique. The reaction in solution gave open-cage fullerene derivative 1 in 44% yield by a one-pot reaction. In contrast, the solid-state reaction afforded dimeric derivative 2 as the sole product. Dimeric derivative 2 was found to undergo intramolecular [2 + 2] cycloaddtion between the two C(60) cages located in close proximity to give a new C(60) dimer 6 in quantitative yield. The structures of these new derivatives of C(60) were determined by spectroscopic methods, and the electrochemical behavior of 2 and 6 was also studied.     

Reaction of fullerene C60 with 2-azido-4,6-diphenylpyrimidine

The first representative of the pyrimidine-substituted [60]fullereno[1,2-b]aziridines was synthesized by the reaction of fullerene C₆₀ with 2-azido-4,6-diphenylpyrimidine. 2-(Azahomo[60]fullereno)-4,6-diphenylpyrimidine was found to be formed as a by-product. The electrochemical properties of the adducts were studied.