10.1021/acs.orglett.7b01766
The research focuses on the development of a novel, catalyst-free, redox-neutral, and atom-economical method for synthesizing sultams from 2-nitrochalcones and elemental sulfur. The experiments involve heating 2-nitrochalcones with sulfur in the presence of a base such as 3-picoline or N-methylmorpholine, leading to the formation of sultams with complete atom economy. The reaction conditions were optimized through a series of tests, varying the base, temperature, and amount of sulfur. The scope of the reaction was explored with various chalcones bearing different substituents on the benzoyl and nitrobenzene rings. The connectivity of the synthesized sultams was confirmed by X-ray diffraction studies and NMR spectroscopy. The study also investigated the reaction mechanism and found that the choice of basic additive was crucial for the success of the reaction. The research demonstrates a versatile and environmentally friendly approach to synthesizing sultams, which are important scaffolds in medicinal chemistry.
10.1021/jo00298a044
The research investigates the reactivity of monohalonitrobenzenes in alkaline 2-propanol solutions of potassium 2-propoxide, focusing on the competition between radical and nonradical reaction pathways. The study aims to identify distinct reaction paths, including hydro dehalogenation to nitrobenzene, alkoxy dehalogenation via the SNAr mechanism, and nitro reduction to azoxy and anilino derivatives via nitroso intermediates. The research concludes that, with the exception of 2- and 4-fluoronitrobenzene, radical processes are generally faster than the SNAr reaction. The study also reveals that the presence of oxygen and cation complexing agents, such as 18-crown-6, significantly influence the reaction pathways and product distributions. Key chemicals used in the process include various halonitrobenzenes (X = F, Cl, Br, I), potassium 2-propoxide, 2-propanol, and 18-crown-6 ether.
10.1016/S0040-4020(01)88723-8
The research focuses on the synthesis of 5-propynyloxycycloalkane pyrimidines (IIIA, IIIB, IIIC, and IIID) and their selective and reactive behavior in intramolecular Diels-Alder reactions with inverse electron demand, followed by a retro Diels-Alder reaction. The compounds IIIA and IIIB favor the extrusion of X-CH2CN, yielding 3-(3-cyanopropyl)-1,3-dihydro-6-phenyl-R1-R2-furo[3,4-c]pyridines (29-36), while compounds 17 and 21 also yield 4-phenyl-6,7,8,8a-tetrahydro-furo[4,3,2-d]quinoline (38) by expelling HCN or MeCN, respectively. For compounds IIIC and IIID, HCN expulsion is favored over X-CH2CN, leading to the formation of 2H-1,6,7,8,9,9a-hexahydro-4-phenyl-9a-R1-5-aa-l-oxo-benz[~~azulenes (39, 40). The reactivity of these compounds towards cycloaddition is significantly influenced by the nature of the substituent R2 when R1 = H, but less so when R1 = Me. The ratio of products V and VI mainly depends on the nature of -X-. The synthesis of these pyrimidines involves starting from their keto precursors (I) and using various reagents such as NaBH4, Grignard reagents, and propargyl bromide in the presence of sodium hydride. The intramolecular Diels-Alder reactions are performed by heating the compounds III in nitrobenzene at 140°C, and the products are analyzed using 1H-NMR spectroscopy.
10.1021/jo00191a003
The study explores a direct method for the periodination of aromatic compounds using periodic acid (HIO?) and iodine in concentrated sulfuric acid. This method allows for the exhaustive iodination of unactivated aromatic substrates such as benzene, nitrobenzene, benzoic acid, chlorobenzene, phthalic anhydride, and toluene, converting them into their respective periodo derivatives. The study also reports the conversion of benzonitrile to pentaiodobenzamide. The direct periodination method is compared favorably to the existing mercuration/iododemercuration sequence in terms of reaction time and purity of products. The study highlights the versatility of the method, demonstrating that partially iodinated products can be obtained under less vigorous conditions. Additionally, the study discusses the limitations of the method, noting that certain activated aromatics and easily oxidized substrates do not fare well under these conditions. The research provides detailed experimental procedures and characterizations of the synthesized compounds, contributing to the field of organic chemistry by offering a more efficient route for the preparation of polyiodinated and periodinated aromatic compounds.
10.1021/op400317z
The study presents an improved route for the synthesis of a MET kinase inhibitor, LY2801653, which is a small molecule with potential therapeutic applications in various types of cancers. The new synthesis process is more efficient, yielding a 22% overall yield over eight steps, compared to the initial 12-step process with a 5.4% yield. Key steps in the process include a Cu-catalyzed cyclization to form an N1-methylindazole ring, selective nitro reduction, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection. The chemicals used in the study serve various purposes: 3-hydroxybenzaldehyde as the starting material, copper catalyst for cyclization, nitrobenzene for the formation of aryl ether, and Boc-protected pyrazole as a key intermediate. The study also addresses safety concerns and optimizes the synthesis for multikilogram operations, focusing on minimizing the use of hazardous chemicals and improving the overall efficiency of the process.
10.1039/c39870001373
The study investigates a new method for preparing diphenyl ethers by displacing an aromatic nitro group with phenoxides. It involves using substituted nitrobenzenes (2a-d) and various phenoxides, including sodium phenoxide and 2,6-disubstituted phenoxides, in dry dimethyl sulphoxide at 90°C for 16 hours. The nitrobenzenes act as the substrates, while the phenoxides serve as nucleophiles to displace the nitro group, forming diphenyl ethers. The study highlights that this method is particularly effective for synthesizing hindered diphenyl ethers from weakly nucleophilic phenoxides. The results show that the yield of diphenyl ethers is affected by the reaction temperature and the specific phenoxide used. Additionally, the study provides insights into the reaction mechanism, suggesting a radical nature rather than an anionic nucleophilic displacement mechanism in certain cases.
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