Refernces
10.1002/cssc.201100649
The research focuses on the synthesis of functional acetylene derivatives from calcium carbide, exploring its potential as a sustainable feedstock for the chemical industry. The study addresses the challenges of calcium carbide's low solubility and difficulty in controlling mono-substitution reactions by developing efficient catalytic protocols for the synthesis of various functional acetylene derivatives. The experiments involve the use of calcium carbide as a nucleophilic carbon source in AAA (aldehyde, alkyne, amine) and AHA (alkyne, haloalkane, amine) coupling reactions, utilizing copper catalysts such as CuCl and CuI. Reactants include calcium carbide, various aldehydes or ketones, amines, and copper catalysts, with solvents like dichloromethane and acetonitrile. The analyses used to monitor the reactions and characterize the products encompass thin-layer chromatography, gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy, providing detailed information on the chemical shifts, multiplicity, coupling constants, and integration of the synthesized products.
10.1016/S0040-4039(00)96887-4
The research aimed to explore the preparation and reactivity of simple 5,6-dihydropyridinium salts, specifically focusing on the simplest member of this class, 2 (R1 = alkyl, R2 = H), as new synthons for the synthesis of functionalized piperidine systems. The study commenced with the preparation of the starting N-methyl A2-piperidone 1, which was then reacted with acetyl chloride to form the dihydropyridinium salt 2. This salt was found to be sensitive to temperature but could be efficiently reacted with a series of Grignard reagents at -50°C, leading to the formation of C-2 substituted enol acetates 6a-f with yields ranging from 50-93%. The research concluded that these reactions were reproducible on both small and large scales, provided attention was paid to experimental details. The study also demonstrated a synthetic application of synthon 1 by converting the Grignard addition product to benzomorphan 12 in three steps, showcasing a method for double substitution at the C-4 position of the piperidine ring. Key chemicals used in the process included acetyl chloride, Grignard reagents, and various piperidone derivatives.
10.1016/S0040-4039(03)00420-9
The research focuses on the concise and stereoselective synthesis of racemic erythro-methylphenidate (1), a compound that, despite its limited therapeutic properties, can be useful for the resolution and epimerization of the erythro-isomer. The study aims to develop a new synthetic strategy for this compound, starting from piperidine-2-one and employing a modified Eschenmoser sulfide contraction reaction. Key chemicals used in the process include piperidine-2-thione (3), 2-bromo-2-phenylmethylacetate (4), and various reducing agents such as NaBH4/AcOH, NaCNBH3/HCl, and NaHB(OAc)3/AcOH. The researchers successfully synthesized (+/?)-erythro-methylphenidate in three steps with an overall yield of 52%, while also observing the concurrent formation of thiazolidinone 5, which is subject to ongoing investigation regarding its formation mechanism. The study concludes with a novel and efficient method for synthesizing (+/?)-erythro-methylphenidate, highlighting the importance of reaction conditions in controlling the formation of desired products.
10.1039/c4cc02645d
The study presents an efficient synthetic route to produce tosyl-protected (2S)-phenyl-3-piperidone, a common intermediate for many drugs, from biomass-derived furfural. Furfural, a platform chemical derived from agricultural waste like rice straw, is transformed into the piperidone core structure through a series of reactions involving 4-methylbenzenesulfonamide, a Lewis acid catalyst, and a rhodium-catalyzed asymmetric arylation. The aza-Achmatowicz rearrangement and hydrogenation steps further convert the intermediate into the desired piperidone. The synthetic utility of this piperidone is demonstrated by synthesizing a NK1 receptor antagonist. This method is advantageous due to its short synthetic route, high yield, minimal loss of optical purity, and the use of a renewable biomass-derived starting material, addressing sustainability and environmental concerns associated with traditional methods and the disposal of agricultural waste.
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