Solvent purification, monitoring

At Merck KGaA in Darmstadt (Germany), in-line UV spectroscopy has been used for monitoring a distillation setup for solvent purification." A transmission probe was implemented at the top of the column. Solarization-resistant UV fibers guided the light to a diode array spectrometer. From the spectra, a quality parameter was extracted and fed to the process control system (PCS). As an example, the quality parameter would exhibit a transient behavior upon column startup. Below a defined threshold value of the parameter, the PCS would assume sufficient product quality and switch the exit stream from waste to product collection. The operation of the spectrometer does not take place in a direct manner, but rather via the PCS. 

In addition to the insoluble polymers described above, soluble polymers, such as non-cross-linked PS and PEG have proven useful for synthetic applications. However, since synthesis on soluble supports is more difficult to automate, these polymers are not used as extensively as insoluble beads. Soluble polymers offer most of the advantages of both homogeneous-phase chemistry (lack of diffusion phenomena and easy monitoring) and solid-phase techniques (use of excess reagents and ease of isolation and purification of products). Separation of the functionalized matrix is achieved by either precipitation (solvent or heat), membrane filtration, or size-exclusion chromatography [98,99]. 

Boc-vsAla-OEt (250 mg, 0.89 mmol) was treated with 3M HCI in MeOH (5mL) at 0°C under N2. The mixture was stirred at rt for 3 h, monitoring the disappearance of the starting material by TLC (hexane/ EtOAc 6 4). The solvent was concentrated under reduced pressure and the product dried in vacuo yield 192 mg (quant). The hydrochloride salt was used in the subsequent reaction without further purification. 

The alcohol (10 mmol) and methyl iodide (11 mmol) were added to a two-phase system of CS2 (10 ml) and 50% aqueous NaOH (from 5 g NaOH in 5 ml H20) containing n-Bu4NHS04 (lmmol) in a 50 ml round-bottomed flask. The mixture was stirred vigorously at room temperature by a magnetic stirrer. The reaction was monitored by checking the H NMR spectrum of the CS2 layer. To work up the reaction, the CS2 layer was separated and the aqueous layer extracted three times with CS2 (3 X10 ml). The combined CS2 layers were dried (Na2S04) and filtered. Evaporation of the solvent under reduced pressure afforded pure 0-alkyl 5-methyl dithiocarbonate (Table 2.5). Further purification could be carried out by column chromatography on silica gel or recrystallization for solid samples. 

A mixture of benzaldehyde la (0.53 g, 5 mmol), paraformaldehyde (1 g, 30 mmol) and solid sodium hydroxide (0.16 g, 4 mmol) were taken in an Erlen-meyer flask and placed in a commercial microwave oven operating at 2450 MHz frequency. After irradiation of the mixture for 25 s (monitored by TLC), it was cooled to room temperature, extracted with chloroform and dried over anhydrous sodium sulfate. Then the solvent was evaporated to give the corresponding ben-zylalcohol 2a in 90% yield exclusively without the formation of any side products. Preparative column chromatography with silica gel was used for further purification of the alcohols, eluting with petroleum ether (60/80)-CHCl3 (1 1). 

Benzoin la (2 mmol) and zeolite A (2 g) were mixed thoroughly in a mortar and the mixture was transfered to a beaker and irradiated for 6 min. The progress of the reaction was monitored by TLC using CH2CI2 as solvent. The mixture was extracted into methylene chloride and then filtered. The solvent was removed under reduced pressure to afford pure benzil 2a (340 mg, 80%). Further purification was carried out by column chromatography (CH2Cl2-light petroleum, 80 20, v/v) and crystallization in EtOH. 

The sulfide 1 (0.75 mmol) is dissolved in dichloromethane (2-3 mL) and adsorbed over silica supported sodium periodate (20%, 1.36 g, 1.28 mmol) that is wetted with 0.3 mL of water by thoroughly mixing on a vortex mixture. The adsorbed powdered material is transferred to a glass test tube and is inserted in an alumina bath (alumina 100 g, mesh 65-325, Fisher scientific bath 5.7 cm diameter) inside the microwave oven. The compound is irradiated for the time specified in the table and the completion of the reaction is monitored by TLC examination. After completion of the reaction, the product is extracted into ethyl acetate (2x15 mL). The removal of solvent at reduced pressure affords crude sulfoxide 2 that contains less than 5% sulfone. The final purification is achieved by column chromatography over silica gel column or a simple crystallization. 

Aldehyde or ketone (3 mmol), ammonium acetate (3 mmol, 231 mg), basic alumina (3 g) and active methylene compound 2 (3 mmol) were mixed thoroughly in a mortar. The reaction mixture was placed in a beaker and irradiated under the conditions shown in Table. The progress of reaction was monitored by TLC using petroleum ether-CH2Cl2 (30 70) as eluent. The mixture was extracted into CH2C12 then filtered and washed with water. The solvent was removed under reduced pressure by rotatory evaporator. Further purification by column chromatography on silica gel gave the desired product. 

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