Removal of Solvent Under Reduced Pressure

Concentration of solvent under reduced pressure is very efficient. It reduces the time for solvent removal in microscale experiments to a few minutes. In contrast, distillation or evaporation procedures require many minutes for even relatively small volumes. Several methods are available. 

Filter Flask Method. This vacuum-concentration technique can be tricky and should be practiced prior to committing hard-won reaction product to this test. The procedure is most useful with fairly large chroma ographic fractions (5-10 mL).The sequence of operations is as follows (see also Fig. 5.39)  

Step 1. Transfer the chromatographic fraction to the 25-mL filter flask. Step 2. Insert the 11-mm Hirsch funnel and rubber adapter into the flask. 

Step 3. Ttom on the water pump (with trap) and connect the vacuum tubing to the pressure flask side arm while holding the flask in one hand. 

Step 4. Place the thumb of the hand holding the filter flask over the Hirsch funnel filter bed to shut off the air flow through the system (see Fig. 5.39). This win result in an immediate drop in pressure. The volatile solvent wiU rapidly come to a boil at room temperature. Thumb pressure adjusts air leakage through the Hirsch funnel and thereby controls the pressure in the system. It is also good practice to learn to manipulate the pressure so that the liqiiid does not foam up into the side arm of the filter flask. 

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Alkvl Azides from Alkyl Bromides and Sodium Azide General procedure for the synthesis of alkyl azides. In a typical experiment, benzyl bromide (360 mg, 2.1 mmol) in petroleum ether (3 mL) and sodium azide (180 mg, 2.76 mmol) in water (3 mL) are admixed in a round-bottomed flask. To this stirred solution, pillared clay (100 mg) is added and the reaction mixture is refluxed with constant stirring at 90-100 C until all the starting material is consumed, as obsen/ed by thin layer chromatographv using pure hexane as solvent. The reaction is quenched with water and the product extracted into ether. The ether extracts are washed with water and the organic layer dried over sodium sulfate. The removal of solvent under reduced pressure affords the pure alkyl azides as confirmed by the spectral analysis. ... 

Resins 2 and 3 are treated with dichloromethane containg 3% and 1.5% trifluoroacetic acid (lOmL/g resin), respectively, for 18 h. The resin is filtered off and washed twice with dichloromethane (10 mL / g of resin). The filtrate is washed with saturated NaHCCL (5 mL) and brine (5 mL), and the organic phase is separated and filtered through a short path silica gel column to obtain a colourless solution. In the case of polymer-bound allyl esters giving rise to cleavage products of type 5f, the aqueous workup is omitted. The products obtained after removal of solvent under reduced pressure contain small amounts of silanol by-products (note 5), which is to be accounted for in the calculation of cleavage yields. 

Reaction of Ethylenediamine in Absence of Copper Ion. Using 0.015 mole of ethylenediamine and omitting copper ion, only 4-iminopentane-2-one was obtained after removal of solvent under reduced pressure [0.4 gram (40%) white crystals, b.p. 80 -82° 2 mm.]. 

H-m-Amb-OH (2 0.75 g, 5 mmol) was dissolved in H20 (5mL) (the pH was adjusted to 8 by the addition of TEA). To this soln at 0 °C was added Fmoc-OSu (1.5 g, 4.5 mmol) in MeCN (5 mL). The pH of the soln was monitored and kept at -8 by addition of TEA. With the pH constant, the mixture was allowed to stir at rt for 3 h. The mixture was then filtered, and the solvent was removed under reduced pressure. The isolated residue was added to vigorously stirred 1 M HCI. The resulting precipitate was collected by filtration, dissolved in EtOAc, and washed with several portions of 1M HCI. After removal of solvent under reduced pressure, the product was purified by recrystallization (EtOAc/hexane) to give Fmoc-m-Amb-OH yield 1.27 g (68%) mp 200-201 °C. 

Freshly prepared NaBH4-alumina (1.13 g, 3.0 mmol of NaBH4) is thoroughly mixed with neat acetophenone Id (0.36 g, 3.0 mmol) in a test tube and placed in an alumina bath inside the microwave oven and irradiated (30 s). Upon completion of the reaction, monitored on TLC (hexane-EtOAc, 8 2, v/v), the product is extracted into ethylene chloride (2x15 mL). Removal of solvent under reduced pressure essentially provides pure sec-phene thy 1 alcohol 2d in 87% yield. No side product formation is observed in any of the reactions investigated and no reaction takes place in the absence of alumina. 

A mixture of p-chlorobenzaldehyde If (0.7 g, 5 mmol), aniline 2f (0.455 g, 5 mmol) and montmorillonite K-10 clay (0.1 g) contained in a 25-mL beaker was placed in an alumina bath inside the microwave oven and irradiated for 2 min. The in situ generated Schiff s base was mixed thoroughly with freshly prepared NaBH4-clay (5.0 mmol of NaBH4 on 1.72 g of reagent) and water (1 mL). The reaction mixture was again irradiated for 30 s (65 °C). Upon completion of the reaction, monitored on TLC, the product was extracted into methylene chloride (3x 15 mL). The removal of solvent under reduced pressure provided pure /V-phe-nyl-p-chlorobenzylamine 4f in 90% yield. The identity of the product was confirmed by formation of the hydrochloride salt, mp 209-211 °C. 

Preparation of 2-(p-Chloroethoxy)Ethyl Diethylphenylacetate 19.2 grams of the foregoing acid was added to a solution of 4 grams of sodium hydroxide in 40 ml ethylene glycol. 28.6 grams p,P -dichlorodiethyl ether was added and the mixture refluxed for 1 hour. After removal of solvent under reduced pressure, 150 ml water was added to the residue and the product extracted with ether. The ethereal solution was dried, concentrated and the residue distilled in vacuo to yield the product as an oil, BP 140°C/0.7 mm. 

Dipyridyl ligand 117 (0.125 g, 0.142 mmol) was dissolved in a 3 1 CHC13/CH3CN solvent mixture (10mL). A chloroform solution (2mL) of trans-bis-benzonitrile palladium(II)dichloride (0.0543 g, 0.142 mmol) was added dropwise to the reaction mixture, which was then refluxed for 8h. The crude reaction mixture was filtered through celite to remove any precipitate, and this was followed by the removal of solvent under reduced pressure. The resulting solid was dissolved in a minimum amount of dichloromethane and precipitated with hexanes to remove residual benzonitrile, and the precipitate was filtered to afford [2]catenane 118 (0.129 g, 87%). 

The aqueous layers containing the silver(I) complex of methyl (lR,5R)-5-hydroxy-2-cyclopentene-l-acetate are then treated with an excess of saturated brine to precipitate silver chloride and free the desired product. After precipitation is complete, the water layer is decanted from the solid silver chloride. The solids are washed with ether (4 x 100 mL) and each ether layer is used to extract the water layer (Note 20). The combined ether layers are washed with 50 mL of brine and dried over anhydrous magnesium sulfate. Filtration and removal of solvent under reduced pressure yield 16-19 g of crude product. The product is distilled through a 4"-Vigreux column at 0.1 mm pressure to yield 12.8-14.7 g (27-31 ) of methyl (lR,5R)-5-hydroxy-2-cyclopentene-l-acetate, bp 74-78°C at 0,1 mm, [a]p5 -132° (CHjOH, a 1.06) (Notes 21, 22). 

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