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Indole ring is widely represented in natural compounds, as well as in a great variety of drugs. In this paper, the synthesis of a 5-hydroxybenzoindole derivative carrying a pyridyl substituent on position 1 is reported. The method involved no chromatography for purification and used solvents and catalysts of very low toxicity.

Aryl and heteroaryl iodides have been efficiently converted into the corresponding thioacetates in cyclopentyl methyl ether (CPME), a green solvent, under Cu catalysis. The chemoselectivity of the reaction is mainly controlled by electronic factors, enabling the conversion of both electron-rich and electron-deficient substrates into the corresponding thioacetates in good to excellent yields. The products can be easily deprotected to the corresponding thiolates to carry out additional synthetic transformations in situ. Surprisingly, despite CPME’s relatively low dielectric constant, the reaction rate significantly increased when conducted under microwave irradiation conditions. This synthetic methodology exhibits a remarkable tolerance to functional groups, mild reaction conditions, and a wide substrate scope, utilizing a safe and inexpensive CuI pre-catalyst in the green solvent CPME. A non-aqueous workup allowing for the complete recovery of both catalyst and solvent makes this approach an environmentally sustainable protocol for C(sp2) sulfur functionalization. Additionally, the reaction shows selective cross-coupling with iodides in competition with chlorides and bromides, allowing its use in multistep syntheses. To demonstrate the potential of this methodology, it was applied to the high-yield synthesis of a photochromic dithienylethene, where a selective synthesis had not been reported before.

In this work, a novel capsule phase microextraction (CPME) method coupled to high performance liquid chromatography with diode array detection (HPLC-DAD) was developed and validated for the determination of coumarin in bakery products, in accordance with the European Commission Regulation (EC) 1334/2008. The CPME extraction protocol was optimized after examining the following critical parameters: a) selection of the CPME membrane, b) sample loading time c) type of elution solvent, and d) desorption time. The optimum extraction parameters involved the use of a sol-gel CPME capsule (1 cm length), 1 mL of sample loading volume, elution with 3 mL of methanol, the stirring was set at 350 rpm, while the absorption time was 20 min and the desorption time was 15 min. The developed CPME-HPLC-DAD method was validated in terms of selectivity, linearity, accuracy, and precision and showed satisfactory results. The LOD and LOQ were equal to 0.18 µg/g and 0.48 µg/g, respectively. Trueness was assessed by means of relative percentage of recovery and ranged between 83 to 91% for intra-day experiments, and between 81-86% for inter-day experiments, respectively. The green character of the proposed method was examined using complexGAPI index. The method was successfully applied in the analysis of coumarin in bakery products.

Cyclopentyl methyl ether (CPME) has been used in chemical synthesis as an alternative to hazardous solvents. According to some earlier investigation by others, CPME has low acute or subchronic toxicity with moderate irritation and negative mutagenicity and negative skin sensitization (Local Lymph Node Assay). Calculated Permitted Daily Exposure (PDE) value of CPME obtained by our 28-day oral toxicity test is 1.5 mg/day, and CPME is thus assumed to be a class 2 equivalent solvent in the ICH (International Conference on Harmonization) Harmonized Tripartite Guideline Q3C (R5). Wide synthetic utility and a detailed toxicity study suggest CPME as a green and sustainable solvent of choice for modern chemical transformations.