Letters in Organic Chemistry - Volume 9, Issue 3, 2012

One pot three-component reaction of 2-amino pyridines, aldehydes and isocyanides in the presence of silicasupported perchloric acid (HClO4-SiO2), produces 3-aminoimidazo[1,2-a] pyridines in excellent yields. The reaction time is short and work up of reaction is very easy. New compounds were identified by IR, 1H NMR, 13C NMR and Mass spectrum.

1,2,3-triazoles were synthesized using several alkynes and azides as starting materials in the presence of catalytic amounts of Cu-Fe nanoparticles. The process represents many advantages because it does not require additional bases or reductants, and this is carried out under ambient pressure and temperature with good yields.

A simple and efficient protocol for the chemoselective mono-N-Boc protection of various structurally diverse amines with di-tert-butyl dicarbonate using magnetically recoverable γ-Fe2O3@SiO2 nanoparticles is reported. The catalyst can be easily recovered and recycled without a significant loss in the catalytic activity. No competitive side reactions, such as formation of isocyanate, urea, oxazolidinone, and N,N-di-Boc derivatives were obsereved.

(Z)-4,5,8,9-Tetrahydro-3H-oxonin-2-one is the core of naturally occurring topsentolides, cytotoxic oxylipins isolated from a marine sponge of the genus Topsentia. An enantiodivergent approach to topsentolide analogues was worked out with a lipase-catalyzed kinetic resolution of a secondary alcohol and a ring-closing metathesis giving the unsaturated nine-membered lactone as key steps.

The nucleophilic aromatic substitution reaction of pentafluorobenzene, methyl 2,3,4,5-tetrafluorobenzoic acid ester and 1,2,4,5-tetrafluorobenzene with substituted thiophenols showed good regioselectivity while pentafluorobenzene gave high yields. The computational results suggest that the specificity difference between polyfluorobenzenes originates from their electronic properties.

Some important cis- and trans-alkyl substituted glycolurils were prepared via condensation of vicinal dicarbonyl compounds with urea and/or methylurea catalyzed by 0.95 mol% of Keggin- type H3PW12O40 under environmentally benign and simple condition. Proficiency of structurally different heteropolyoxometalates, including Keggin, Wells-Dawson, and Preyssler, was investigated in the reaction of urea with 2, 3-butanedione. A common method was introduced for the isolation of cis- and trans-isomers, role of different solvents was studied, and effect of catalyst mol% was also investigated in this reported.

Treatment of 3-acetylindoles 1(a-e) with ethyl chloroacetate in the presence of K2CO3 and tetrabutylammoniumbromide (TBAB) as phase transfer catalyst in DMF, resulted in the formation of the corresponding N-substituted derivatives, ethyl 2-(3-acetyl-1H-indol-1-yl)acetate 2(a-e) which on reaction with NaBH4 yielded, unexpectedly, ethanol derivatives, 1-(1-(2-hydroxyethyl)-1H-indol-3-yl)ethanone 3(a-e) by the unusual and chemoselective reduction of ester grouping in preference to the acetyl group. Alternative synthesis of the latter was achieved by the treatment of 1(a-e) with 2-chloroethanol under phase transfer catalytic conditions (PTC). 1(a-e), on treatment with benzenesulphonyl chloride, under PTC conditions, yielded the corresponding N-benzenesulphonyl-3- acetylindoles 7(a-e), which on reduction with NaBH4 in methanol afforded the corresponding hydroxy derivatives Nbenzenesulphonyl-( α-hydroxyethyl)indoles 8(a-e). These reactions throw light on the ease of reduction of the 3-acetyl group on indoles with NaBH4.

A facile, efficient and environment-friendly protocol for the synthesis of 3-aminoimidazo[1,2-a]pyridines has been developed by one-pot condensation of 2-aminopyridine, aromatic aldehyde and alkyl or aryl isocyanide in the presence of P2O5 as catalyst under solvent-free conditions at room temperature. The present approach offers the advantages of clean reaction, simple methodology, short reaction time, high yield, easy purification, and economic availability of the catalyst.

Glycyrrhetinic acid (GA) is a commonly used drug for the chemotherapy of Chronic Hepatitis B, allergic dermatitis, inflammation, etc. But some problems such as poor water-solubility, low bioavailability and short plasma halflife, have limited its use. In the present study, PEGylation derivatives of GA derivatives were synthesized and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, etc. The PEG-GA conjugates having a critical micelle concentration of 0.081-0.73 mg/mL were used to form nano-sized micelles, with mean diameters of 120.86 ± 31.74 nm. The physico-chemical properties of the PEG-GA conjugate were evaluated including stability, cellular toxicity, and drug release profile. All the conjugates synthesized showed good stabilities in acidic and neutral solutions, while the stability in alkaline solution and the enzymatic hydrolysis rate, were significantly affected by the linkage between the GA and PEG chain. The results demonstrate that, by PEGylation of GA derivatives, the greatly increased water solubility and desirable self-assembly abilities of PEG-GA were obtained. The novel conjugates have potential medical applications for intravenously delivery of insoluble drug delivery.

Phenothiazinyl primary amines were synthesized in moderate to excellent yields from cyano (oligo)phenothiazines by reduction with LiAlH4 in diethyl ether or with nBuNBH4 in dichloromethane. All representatives show first reversible oxidation waves, they are UV absorbing and dimers emit blue-green light upon UV excitation with substantial quantum yield.

A facile two step synthesis of 3-aroylcoumarin-flavone hybrids was achieved from 7-hydroxyflavone and α- oxoketene dithioacetals. In the first step 7-hydroxyflavone was regioselectively formylated under Duff reaction conditions. Resulting 8-formyl-7-hydroxy flavones were condensed with α-oxoketene dithioacetals in the presence of a catalytic amount of piperidine to furnish 3-aroylcoumarin-flavone hybrids.

Aza-Diels-Alder reaction between imines and 2,3-dihydrofuran under radical cation induced conditions was achieved and series of hexahydrofuro[3,2-c]quinoline derivatives was prepared. The stereoselectivity was affected by the substituents on imines, which revealed a stepwise mechanism. A radical cation mediated mechanism was proposed to rationalize the formation of the products.

Benzylamine in combination with acetic acid was identified as a powerful catalyst for the condensation of oxindole with aldehydes, acetone or cyclic ketones. A variety of 3-alkyloxindoles could be readily prepared in 10 mmol scale via the sequential benzylamine acetate catalyzed condensation of oxindoles with aldehydes (or ketones) and conjugate reduction by NaBH4.