Diastereoselective Aldol Condensation - Essay Example

1. Procedure A. (S)-3 Oxopropyl)-4-(phenylmethyl)-2-oxazolidinone. The first step of this procedure is to add 17.7 g of (S)-4-(phenylmethyl)-2-oxazolidinone into a 500ml flask, which is then capped with rubber septum. Nitrogen is used for flushing the compound. A cannula is then used to add anhydrous tetrahydrofuran to the flask. At this point, the ice bath is used to cool the solution in the flask to a temperature of -780 C. Then a cannula is used to transfer the solution of 1.47M butyllithium and hexane into a 100 mL calibrated cylinder, which should have a joint that is made of ground-glass. The cylinder should be dry and septum-stoppered. Then the solution is put in a reaction flask for a period of 10 minutes. During or after this time, the solution’s color could become yellow as well as slightly cloudy.The third step is the addition of 9.6 mL of propionyl chloride into the butyllithium solution by the use of a syringe. After this addition, the resulting solution is usually clear and almost colorless. This solution is stirred for a period of 30 min while it is still at the -70 C. After stirring, the temperature of the solution is then increased to an ambient temperature over a period of 30 minutes. In order to quench any excessive propionyl chloride, a 60 mL solution of saturated ammonium chloride should be added to the above solution. Similarly, any excess tetrahydrofuran and hexane should also be removed by the use of a rotary evaporator, which should be at temperatures of between 250 – 300 C. Then the suspension that results is extracted by the use of dichloromethane in two 80 mL portions. These extracts are then washed in a solution of 75mL 1M sodium hydroxide as well as a solution of 75mL brine. Anhydrous sodium sulfate is then used to dry the extracts, before filtration. In order to remove the solvent, rotary evaporation is used. After this removal, a residue that is an oil of light yellow color is left and it is crystallized by placing it in a refrigerator overnight. Once the crystalline solid is obtained, it should be pulverized as well as triturated using the least possible amount of cold hexane. Once filtration and drying are done, a quantity of between 21.2 – 22.3 g, which is equivalent to 91% - 96%, of the product that should result from this procedure is obtained in the form of a crystalline solid. This solid is usually colorless. B. The boron aldol reaction The first step involves the addition of 21.2g of acylated oxazolidinone into a 2L flask, which should be dry and should have a large magnetic bar for stirring purposes. Rubber septum is also used to seal the flask whereas nitrogen is used for sweeping purposes. Then a syringe is used to measure 200ML of a solvent (anhydrous dichloromethane) and introduce it into the flask. You should then cool the contents of the flask to the temperatures of 00 C using an ice bath. After the cooling, a syringe is used to add 27mL of dibutylboron triflate. You should then add 16.7mL of triethylamine in drops to ensure that the temperature does not rise above 30 C. During the addition of these two compounds, the contents of the flask turn yellow or green and light yellow respectively. Replace the ice bath with ice-acetone bath and let the internal temperatures drop to less than -650 C. Then you should use a syringe to add freshly distilled benzaldehyde (10.3mL) to the flask. The addition should take place over a period of 5 minutes. At this point, stir the solution for 20 minutes within the bath of ice-acetone. Then transfer the solution to the temperature of the ice-bath and stir for one hour. In order to quench this mixture, add 100mL of aqueous phosphate buffer, which should be at a pH of 7, and 300mL of methanol. Then a syringe is used to add 300mL solution of methanol and 30% aqueous hydrogen peroxide, which are in the ratio 2:1. This addition should be at a rate that will keep the temperatures less than 100C. A rotary evaporator is then used to remove the volatile material at temperatures of 25-300C. Divide diethyl ether into three portions of 500mL each, which are used toe extract the suspension. Then 5% of aqueous sodium bicarbonate as well as 500mL of brine are used to wash the organic extracts. Anhydrous magnesium sulfate is then used to dry the extracts whereas a rotary evaporator filters and concentrates the extracts. This process should produce 35-36g of a solid that is white in color. C. Chiral auxiliary removal Aldol adduct and a solution of tetrahydrofuran/distilled water (ratio 4:1) in the quantities of 8.48g and 125mL respectively are added to the 500mL flask, which should have a magnetic bar for stirring. After this addition, rubber septum is used to seal the flask, nitrogen purges and the temperatures are reduced to 00C. Then a syringe is used to add 10.2mL of 30% aqueous hydrogen peroxide in a duration of 5 minutes. Then add 0.96g of a lithium hydroxide dissolved in 50mL of water that is distilled. At this point, some gas will evolve from the solution. This solution is then stirred for a period of 1hr, the septum is removed, and a solution of 12.6g of sodium sulfite and 75mL of water that is distilled are added to the solution in the flask. A rotary evaporator removes any excess tetrahydrofuran at temperatures of between 25 and 300 C. The dicholoromehtane is divided into three 100mL portions for the purposes of removing oxazolidinone auxiliary. The obtained aqueous solution is then cooled using an ice bath and its acidity increased to PH1 by adding a solution of aqueous hydrocholoric acid. Ethyl acetate is then divided into five 100mL portions for extracting the resultant solution that contains hydroxyl acid. The obtained extracts are then dried using anhydrous magnesium sulfate, they are filtered and then concentrated. This results in a powder that weighs 5.1g. This crystalline solid is then dissolved in a 200Ml solution of 5% sodium bicarbonate. Dicholoromethane is then divided into 100mL portions for extracting the above solution. The extract is then acidified before using ethyl acetate for another extraction as previously done. These concentrates are dried using anhydrous magnesium sulfate. They are then filtered and concentrated via rotary rotation. This results in 4.35g of ozazolidinone auxiliary, which is some white crystalline solid. This solid is then recrystallized in 50mL of ethyle acetate-hexane (ratio 2:1), a process that produces 3.95g of oxazolidinone white crystals. Magnesium sulfate is used to dry the ethyl acetate extracts, which are then filtered and concentrated to produce 4.5g of hydroxyl acid in the form of some white crystalline solid. This solid is then recrystallized using ca. 20mL of carbon tetrachloride. This results in a quantity of 4-4.03g of pure 3—hydroxy-3-hydrox-3-phynyl-2-mehtylpropanoic acid. Read More