Synthesis of Functionalized Pyrroles by Reaction of 3,4‐Diacetylhexane‐2,5‐dione with Primary Amines in Water

3,4‐Diacetylhexane‐2,5‐dione (tetra‐acetylethane) undergoes a complex reaction with primary amines in boiling water to produce N‐alkyl‐3‐acetyl‐2,5‐dimethylpyrroles, together with small quantities of N‐alkyl‐3,4‐diacetyl‐2,5‐dimethylpyrroles and 2,5‐dimethyl‐1H‐pyrrol‐3‐yl‐vinyl‐acetamides. When the reaction was carried out in methanol at room temperature, the yields of the latter products increased.     

Efficient synthesis of functionalized spiro-2,5-dihydro-1,2-λ-oxaphospholes

The reaction of ethyl propiolate with triphenylphosphine (Ph₃P) in the presence of N-alkylisatins led to ethyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-4-carboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones in good yield. The reaction of dialkyl acetylenedicarboxylates with Ph₃P in the presence of N-alkylisatins led to dialkyl 2,2,2-triphenyl-2,5-dihydro-1,2-λ⁵-oxaphosphole-3,4-dicarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones and alkyl 4-(alkoxy)-5-oxo-2,5-dihydro-3-furancarboxylate-spiro-1-alkyl-1,3-dihydro-2H-indol-2-ones.     

Kinetics study of electrochemically induced michael reaction of benzoquinones with triphenylphosphine

The electrochemical oxidation of 3,4-dihydroxybenzaldehyde (1), 3,4-dihydroxybenzoic acid (2) and 2,5-dihydroxybenzoic acid (3) were studied in the presence of triphenylphosphine (4) as a nucleophile using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from oxidation of 3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid participate in Michael addition reaction with triphenylphosphine (4). In this work, based on an EC mechanism, the observed homogeneous rate constants (k _obs) of the reaction of produced benzoquinones with triphenylphosphine (4) were estimated by comparing the experimental cyclic voltammograms with the digitally simulated results.     

Manganese (III) acetate mediated synthesis of polysubstituted pyrroles under solvent-free ball milling

Under solvent-free ball milling conditions, a simple and mild method was developed for efficient synthesis of 2,5-dimethyl-3,4-dicarboxylate-pyrroles and N-substituted 3,4-diphenylpyrroles via condensation-annulation of amines with acetoacetate and 2-phenylacetaldehyde, respectively. The use of cheap and safe Mn(OAc)₃ as a mediator, no use of commonly employed acetic acid as solvent, short reaction time and readily available starting materials make this protocol a good alternative to traditional synthesis of polysubstituted pyrroles.     

2,5-Diamidofuran anion receptors

3,4-Diphenylfuran-2,5-dicarboxylic acid bis-N-phenylamide 1 and 3,4-biphenyl-furan-2,5-dicarboxylic acid bis-N-butylamide 2 have been synthesised and shown to act as fluoride selective anion receptors in DMSO-d₆/0.5% water solution.     

Effect of substituents on addition polymerization of norbornene derivatives with two Me3Si-groups using Ni(II)/MAO catalyst

Addition polymerization and copolymerization of bis(Me₃Si)-substituted norbornene-type monomers such as 5,5-bis(trimethylsilyl)norbornene-2, 2,3-bis(trimethylsilyl)norbornadiene-2,5 and 3,4-bis(trimethylsilyl)tricyclo[4.2.1.0^2,5]nonene-7, in the presence of Ni(II) naphtenate/MAO catalyst were studied. Disubstituted norbornene and norbornadiene were found to be practically inactive in homopolymerization. On the other hand, their copolymerization with norbornene proceeded with moderate yields of copolymers containing predominantly norbornene units. Under studied reaction conditions 2,3-bis(trimethylsilyl)norbornadiene-2,5 was transformed into the only exo-trans-exo-dimer as a result of the [2+2]-cyclodimerization reaction. Moving Me₃Si-substituents one carbon atom away from norbornene double bond made 3,4-bis(trimethylsilyl)tricyclo[4.2.1.0^2,5]nonene-7 active in homopolymerization and allowed to obtain addition homo-polymer with two Me₃Si-substituents in each elementary unit. The reaction mechanism and steric effect of Me₃Si-substituents are also discussed.     

Kinetics and mechanism of the chain reaction of N-phenyl-1,4-benzoquinone monoimine with 2,5-dimethylhydroquinone

The kinetics of the reaction of N-phenyl-1,4-benzoquinone monoimine with 2,5-dimethyl-1,4-hydroquinone in chlorobenzene was studied at 298.2 and 340 K. The reaction occurs by a chain mechanism with a chain length of ～10²?10³ units, depending on temperature and reactant concentrations. The orders of reaction with respect to components and the rate constants (or estimated values) were determined for all of the elementary steps at 298.2 and 340 K. The experimental data were compared with the results obtained previously for the reaction of N-phenyl-1,4-benzoquinone monoimine with 2,5-di-tert-butyl-1,4-hydroquinone. The nature of substituents in hydroquinone exerts a strong effect on the kinetic parameters of this new class of chain reactions. The effect of the final product, 2,5-dimethylquinone, on the reaction kinetics at 298.2 and 340 K was studied, and it was found that 2,5-dimethylquinone additives has only a weak inhibiting effect. The rate constant of the reaction of 2,5-dimethylquinone with semiquinone radicals, which were produced from 4-hydroxydipheny-lamine, was estimated: k _?2 ～ 10⁴?10⁵ l mol^?1 s^?1.     

Synthesis of carbazomycin B by radical arylation of benzene

Iodination of 2-methoxy-3,4-dimethyl-5-nitrophenol followed by acetylation yields (6-iodo-2-methoxy-3,4-dimethyl-5-nitrophenyl) acetate. Reduction with iron and acetic acid followed by reaction with methyl chloroformate then provides N-methoxycarbonyl-3-acetoxy-2-iodo-4-methoxy-5,6-dimethylaniline. Treatment of this substance in benzene at reflux with tributyltin hydride and a catalytic quantity of diphenyl diselenide leads to the formation of N-methoxycarbonyl-3-acetoxy-2-(2,5-cyclohexadienyl)-4-methoxy-5,6-dimethylaniline which on exposure to phenylselenenyl bromide affords a phenylselenenyl tetrahydrocarbazole. Oxidation deselenation and rearomatization are achieved by heating with tert-butylhydroperoxide finally affording carbazomycin B after saponification.     

Catalytic asymmetric brominative dearomatization reaction of benzofurans

A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [(DHQ)₂PHAL] as the catalyst and N-bromoacetamide (NBAc) as the brominating reagent. A series of brominated spiro[benzofuran-2,5'-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 97% ee).     

Efficient synthesis of 5-nitro-benzo[b]furans via 2-bromo-4-nitro-phenyl acetates

Acetylation/Sonogashira cross-coupling reaction/cyclization has been carried out in one-pot using a Na₂PdCl₄/2-(di-tert-butylphosphino)-N-phenylindole/CuI system in TMEDA to give 5-nitro-2-substituted benzo[b]furans in excellent yields. We also describe the extension of this method to 4-EWG-2-bromo-phenols obtaining 2,5-disubstituted-benzo[b]furans in good yields.     

Cyclopropanation of 3,4-dihydro-1 H-benzo[e][1,4]diazepine-2,5-diones

A two step parallel synthesis protocol for the preparation of 1N-substituted spirobenzodiazepineones is described. Treatment of 4-methyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione with a series of alkyl halides using a microwave-assisted heating protocol provided N-derivatized compounds, which were transformed to the corresponding cyclopropylamines employing modified Kulinkovich-type reaction conditions. X-ray structural analysis gave conclusive evidence of the newly created spiro centre and revealed a significant flattening of the seven-membered ring system compared with the benzodiazepinedione system providing a characteristically different pattern of bond exit vectors. The physicochemical parameters log D, pK_a, solubility and membrane permeability of both cyclopropanated and precursor compounds were assessed.     

Synthesis of novel 2-phenyl-5-substituted dihydropyrimidines using 2-phenyl-1,3-diaza-1,3-butadienes and electron-deficient olefins

A novel synthetic method for 2,5-disubstituted dihydropyrimidines was developed. The cyclization of 1,3-diaza-4-dimethylamino-1,3-butadienes having a N-protecting group (N-Boc, N-Cbz, N-n-C₄H₉, N-Bn or N-Ph) with electron-deficient olefins, such as α,β-unsaturated carbonyl compounds, phenyl vinyl sulfone, and acrylonitrile was studied in detail. The cyclization smoothly proceeded to afford 4-dimethylamino-1,4,5,6-tetrahydropyrimidines or 1,6-dihydropyrimidines in good yields. The isolated 4-dimethylamino-1,4,5,6-tetrahydropyrimidines were converted to 2,5-disubstituted-1,6-dihydropyrimidines through the β-elimination of the dimethylamino group. 2,5-Disubstituted-1,4(6)-dihydropyrimidines were obtained after removal of the N-Boc or N-Cbz group. Independent tautomers of the resulting dihydropyrimidines were observed.     

Application of dimeric orthopalladate complex of homoveratrylamine as an efficient catalyst in the Heck cross-coupling reaction

The [Pd{C₆H₂(CH₂CH₂NH₂)-(OMe)₂,3,4} (μ-Br)]₂ complex of homoveratrylamine was synthesized and its application in the Heck coupling reaction was studied. This complex had been demonstrated to be active and efficient catalyst for the Heck reaction of aryl iodides, bromides and even chlorides. The cross-coupled products were produced in excellent yields in a short reaction time using catalytic amounts of [Pd{C₆H₂(CH₂CH₂NH₂)-(OMe)₂,3,4} (μ-Br)]₂ complex in N-methyl-2-pyrrolidinone (NMP at 130 °C).     

A mild and efficient aza-Diels-Alder reaction of N-benzhydryl imines with trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene catalyzed by Yb(OTf)3

The aza-Diels-Alder reaction of trans-1-methoxy-2-methyl-3-trimethylsiloxybuta-1,3-diene with N-benzhydryl imines in the presence of Yb(OTf)₃ in toluene at room temperature gave the corresponding 2,5-disubstituted 2,3-dihydro-4-pyridones in high yields. This reaction can also be carried out with diene, aldehydes, and amine in a three-component one-pot reaction manner in moderate to high yields under solvent-free conditions. The relationship between Lewis acids and activity, solvents and catalyst loading were studied. Some investigation towards the reaction mechanism was discussed.     

含氰基基团的以C为中心的不对称阴离子离子液体的合成、表征及应用

首次通过不对称阴离子的钠盐/钾盐和不同的季胺化的咪唑,吡咯溴盐/氯盐进行离子交换,合成了一系列含氰基官能团的不对称阴离子功能化离子液体。通过红外、核磁共振、质谱和元素分析对离子液体的结构进行表征;通过TGA对离子液体的热稳定性进行测定,结果发现不对称功能化离子液体具有良好的热稳定性,其分解温度在219-319℃范围内。将功能化离子液体[Bmim][C(CN)2COCH3]作为弱配体应用于模型的Suzuki偶联反应,发现在反应中加入功能化离子液体[Bmim][C(CN)2COCH3]可以使反应收率提高10-15%。     

Synthesis of imidazolidin-4-one and 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-dione derivatives of primaquine: scope and limitations

The synthesis of imidazolidin-4-one derivatives of primaquine as potential antimalarial agents is described. The target compounds were synthesized in three steps: (i) condensation of (±)-primaquine with N^α-protected amino acids, (ii) removal of the N^α-protecting group, and (iii) reaction of the N-acylprimaquine with a carbonyl compound: acetone, three cyclic ketones and veratraldehyde. Using 2-formylbenzoic acid in the third step afforded 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones. All products were isolated in good to excellent yields. Whereas imidazolidin-4-ones were formed as mixtures of all possible diastereomers in equal amounts, 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones were produced in a stereoselective fashion. The compounds hydrolyse very slowly (t_1/2 5-30 d) in pH 7.4 buffer to release primaquine. These primaquine derivatives are being submitted to biological assays, and preliminary results of their antimalarial activity are quite encouraging.     

An alternative synthesis of benzobis(imidazolium) salts via a ‘one-pot’ cyclization/oxidation reaction sequence

Cyclization of N-aryl and N-alkyl 2,5-diamino-1,4-benzoquinonediimines using paraformaldehyde under acidic conditions followed by oxidation with catalytic amounts of Pd(OAc)₂ afforded their respective benzobis(imidazolium) salts in yields of 48-98%. A comparative solid-state study between a 2,5-diamino-1,4-benzoquinonediimine and its corresponding benzobis(imidazolium) dichloride was also performed.     

Stereospecific epoxide-opening reactions of 1,1-dibromo-3,4-epoxy-1-alkenes with carbon nucleophiles

The stereospecific epoxide-opening reactions of 1,1-dibromo-3,4-epoxy-1-alkenes with allyltributylstannane and with ketene silyl acetals in the presence of a Lewis acid are described. Both the reactions occurred regioselectively at the allylic position via an S_N2 process giving rise to a single product, respectively. Treatment of the products by the latter reaction with p-TsOH afforded various 3,4-anti- and 3,4-syn-disubstituted γ-lactones in a highly stereoselective manner and high yields.     

Preparation and properties of nitrogen-substituted thiosulfinyl compounds and related new heterocycles

The reaction of dilithiated N,N′-dimethyl-1,2-diphenylethylenediamine with disulfur dichloride (S₂Cl₂) gave a thiosulfinyl compound (R₂N)₂SS, 2,5-dimethyl-3,4-diphenyl-1,2,5-thiadiazolidine 1-sulfide, whereas the treatment of dilithiated N,N′-bis(p-toluenesulfonyl)-1,2-diphenylethylenediamine with S₂Cl₂ furnished a new heterocycle, 3,6-bis(p-toluenesulfonyl)-4,5-diphenyl-4H,5H-1,2,3,6-dithiadiazine.     

N-Arylation of azoles with low basicity by 1,4-dimethoxybenzene during undivided electrolysis

The reactions of 1,4-dimethoxybenzene with 4-nitropyrazole, 3,4-dinitro-5-methylpyrazole, 1,2,4-triazole, 3-nitro-1,2,4-triazole, and tetrazole were studied during undivided amperostatic electrolysis on a Pt electrode in MeCN, CH₂Cl₂, and MeOH. The main reaction products were 2-azolyl-1,4-dimethoxybenzenes and (or) 1,4-diazolyl-1,4-dimethoxycyclohexa-2,5-dienes. In all cases except 1,2,4-triazole, N-arylation occurs only in the presence of the Alk₄N⁺ salts of azoles or 2,4,6-trimethylpyridine as a base. The mechanism of the reactions is discussed.