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A three-step diastereoselective synthesis of N-alkylated octahydroacridines has been developed from inexpensive starting materials. Alkylation of cyclohexanone with 2-fluorobenzyl bromide, followed by nitration para to the aromatic fluoro substituent provided the cyclization substrate in 61% yield. Finally, a tandem reductive amination- SNAr cyclization with NaCNBH3 furnished the target compounds in 74-92% yields. X-ray and 1H NMR studies permitted assignment of the stereochemistry of the B-C ring junction. The 3:1-10:1 preference for the cis-isomer was rationalized in terms of steric interactions in the imine reduction and a chair-like conformation for the cyclization. Hydride would be delivered to the molecular face opposite the fluoronitrobenzyl substituent at C-2 of the cyclohexanimine intermediate and the resulting amine would be positioned for addition to the SNAr acceptor ring via a chair-like conformation. [ABSTRACT FROM AUTHOR]

The article presents the study on the tandem reduction-lactamization of ortho-substituted nitroarenes. The study reportedly involved an assessment of the scope of heterocycle synthesis to prepare 2-oxoindolines, 2-oxotetrahydroquinolines, and 2-oxotetrahydro-1H-benzo[b]azepines. The results revealed that the tandem reduction-lactamization sequence allows heterocycles synthesis in a short sequence.

Abstract: A new synthesis of 2,3-dialkyl-4-carbomethoxyisoquinolin-1(2H)-ones and 6,7-dialkyl-8-carbomethoxy-1,6-naphthyridin-5(6H)-ones is reported. The process involves treatment of a β-enaminoester with 2-fluoro-5-nitrobenzoyl chloride, 2-fluorobenzoyl chloride or 2-chloronicotinoyl chloride followed by heating in the presence of base. The conversion, which proceeds by an N-acylation-SNAr reaction sequence, affords 50–86% yields when R1 is n-alkyl but ≤30% yields when R1 is α-branched. [Copyright &y& Elsevier]

A review of the recent literature is given focusing on synthetic approaches to 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions. These syntheses involve: (1) reduction or oxidation followed by cyclization; (2) SNAr-terminated sequences; (3) acid-catalyzed ring closures or rearrangements; (4) high temperature cyclizations and (5) metal-promoted processes as well as several less thoroughly studied reactions. Each domino method is presented with a brief discussion of mechanism, scope, yields, simplicity and potential utility. [ABSTRACT FROM AUTHOR]

The article offers information on the comparative study of the frech catalyst with two conventional catalysts in the Heck synthesis of 2,4-diaminopyrimidine-based antibiotics. It states that nano palladium complexes are reported to be very competent catalysts for cross-coupling reactions which give exceptional yields with low catalyst loading. It also states that the absence of thermal stability and functional group tolerance of many palladium complexes as well as the condition for relatively high catalyst loadings results in the serious limitation on the use of the reactions. It further notes that decomposition of catalysts at normal reaction temperatures can result in extremely contaminated products that need purification.

The article discusses the ammonium chloride-catalyzed synthesis of benzo-fused heterocycles from o-substituted anilines and orthoesters. It also highlights its modified approach in preparing benzimidazoles, benzoxazoles and benzothiazoles from o-substituted anilines and orthoesters using ammonium chloride (NH4Cl) as the catalyst and water or ethanol as the solvent. It further states that benzimidazoles, benzoxazoles and benzothiazoles have been the object of many synthetic studies because of their biological activities including anti-bacterial, anti-cancer and as drugs for the treatment of diabetes.

Four phthalazine derivatives have been prepared from substituted 2-bromobenzaldehyde acetals by a sequence involving: (1) lithiation and formylation; (2) deprotection; and (3) condensative cyclization with hydrazine. Two additional phthalazines were prepared by a similar sequence following direct lithiation of benzaldehyde acetals substituted by anion-stabilizing groups at C3. These syntheses can be conveniently carried out to give phthalazines in overall yields of 40-70%. [ABSTRACT FROM AUTHOR]

An efficient and inexpensive approach to the synthesis of 2-substituted and 2,5-disubstituted 1,3,4-oxadiazoles from arylhydrazides and orthoesters is reported using catalytic NH 4 Cl. The conditions are mild, and thus, compatible with a variety of functional groups. The optimized reaction is performed using 30 mol % of NH 4 Cl in 100% EtOH and is generally complete within 1 h for non-aromatic orthoesters and 2–10 h for aromatic orthoesters. The reaction permits both electron-releasing and electron-withdrawing groups on the arylhydrazide substrate. Most products are formed in high yields and require only minimal purification. Compared with earlier reports, the current reactions proceed in shorter time and require less of the orthoester. [ABSTRACT FROM AUTHOR]

Abstract: Bismuth(III) triflate [Bi(OTf)3] has been developed as an efficient and mild catalyst for intramolecular Friedel–Crafts cyclizations of tertiary alcohols to prepare disubstituted tetrahydronapthalenes, chromans, thiochromans, tetrahydroquinolines, and tetrahydroiso-quinolines. The method represents a unified strategy to synthesize a variety of ring systems from tertiary alcohols using a common Lewis acid. [Copyright &y& Elsevier]

An abstract of the article "Synthesis of a-Aminonitriles under Mild Catalytic, Metal-Free Conditions" by Baskar Nammalwar and colleagues is presented.

An inexpensive and efficient method to synthesize benzimidazole (III), benzoxazole (V) and benzothiazole (VII) derivatives under mild conditions is described. [ABSTRACT FROM AUTHOR]

Flexible Heteroarotinoids (Flex-Hets) are a class of substituted di-aryl compounds that exhibit potent anti-cancer activity without toxicity. They were derived from the more conformationally restricted, 2-atom linker Hets by substitution of the 2-atom linker with a 3-atom urea or thiourea linker, which conferred more potent inhibitory activity against cancer cell lines. The objectives of this structure activity relationship (SAR) study were to determine if a 4-atom acrylamide linker and various substitutions on the terminal aryl ring altered the anti-cancer activity of these second generation Flex-Het compounds compared to the parent Flex-Het compound, SHetA2, which has a thiourea linker and a nitro substituent. Biological activity was measured using a cytotoxicity assay of the human A2780 ovarian cancer cell line treated with a range of compound concentrations. Nitrogen-based substitutions on the terminal aryl group caused similar, but slightly reduced efficacies and potencies. Exceptions were systems that had a nitro group at the para position, the potencies of which were better than that of SHetA2 with efficacies that were only slightly reduced compared to SHetA2. Similarly, the potency of the system with a para dimethylamino group was greater than that of SHetA2. However, a 30% reduction in efficacy compared to SHetA2 was noted. While specific members with the 4-atom acrylamide linker did exhibit excellent potency, the efficacy was slightly below that of SHetA2. Thus, a gradient of activities was observed as the substituent on the aryl ring was altered. [ABSTRACT FROM AUTHOR]