Polyethylene glycol isolation

Reinhoudt, Gray, Smit and Veenstra prepared a number of monomer and dimer crowns based on a variety of substituted xylylene units. They first conducted the reaction of 1,2-dibromomethylbenzene and a polyethylene glycol with sodium hydride or potassium Z-butoxide in toluene solution. Mixtures of the 1 1 and 2 2 (monomer and dimer) products were isolated and some polymer was formed . The reaction was conducted at temperatures from 30—60° and appeared to be complete in a maximum of one hour. The authors noted that the highest yield of 1 1 cyclic product was obtained with disodium tetraethylene glycolate instead of dipotassium hexaethylene gly-colate (see also Chap. 2) . Chloromethylation of 1,3-benzodioxole followed by reaction with disodium tetraethylene glycolate afforded the macrocycle (29% yield) illustrated in Eq. (3.20). 

In 1904 Bally obtained a bluish violet solid by alkali fusion of benzanthrone at approximately 220 °C. Two isomeric compounds were isolated by vatting the reaction mixture and filtering off a sparingly soluble sodium salt. Oxidation of the filtrate gave a blue vat dye, violanthrone (6.75 Cl Vat Blue 20), as the main component. The less soluble residue similarly afforded a violet product, isoviolanthrone (6.76 Cl Vat Violet 10). The formation of isoviolanthrone can be suppressed by carrying out the fusion in a solvent such as naphthalene or a polyethylene glycol in the presence of sodium acetate and sodium nitrite. Dyes of this type are often referred to as dibenzanthrones. 

A reactor charged with sulfopropyldimethylammoniumethyl methacrylate (0.020 mol), a-methoxy-co-methacrylate polyethylene glycol 1000 (0.009 mol), water (398 g), and ethanol (261.90 g) was heated to 78°C. The mixture was then simultaneously treated with ammonium persulfate (0.004 mol) dissolved in water (20 g) over 150 minutes, ammonium persulfate (2.5 g) dissolved in water (60 g) continuously over 120 minutes, sulfopropyldimethyl-ammoniumethyl methacrylate (0.182 mol) over 120 minutes, and a-methoxy-w-meth aery late polyethylene glycol (0.078 mol), and water (205.80 g). Thereafter the reaction was maintained at 70°C for 90 minutes and then cooled. The solution was then treated with water and ethanol removed by distillation. The product was isolated with a solids content of 27.3%, a pH of 2, a Brookfield viscosity of 36 mPa s, and an Mw of 65,000 Da with an M of 8000 Da. 

Under a protective nitrogen blanket, the step 1 product was coupled with methoxy polyethylene glycol prepolymers (Mn 1820 and 4740 Da) using 1,3-dicyclohexylcarbodiimide dissolved in 2 1 . The product was isolated after being purified by precipitation and fractionation from mixed solvents of chloroform/diethyl ether or methanol/diethyl ether. 

A 4-arm polyethylene glycol having an Mn of 10,000 Da (8 mmol of hydroxyl groups) was dried by azeotropic distillation using 400 ml of chloroform. The residue was then redissolved in 300 ml chloroform and cooled to 4°C and then treated with triethylamine (14.4 mmol) and methanesulfonyl chloride (13.2 mmol). The mixture was stirred overnight at ambient temperature and then treated with 5 ml of ethanol and stirred an additional 30 minutes. It was dried using sodium carbonate (10.0 g), concentrated, and filtered. The filtrate was concentrated to dryness and treated with 400 ml of 2-propanol. The precipitate was collected and 20.0 g product isolated having a 95.3% methanesulfonate substitution. 

Polyethylene glycol also has a long history of use as an agent for protein precipitation (4). It shares some of the positive attributes of ammonium sulphate in having a low heat of solution and not promoting denaturation of proteins. It appears that after the addition of polyethylene glycol, proteins are excluded from the space occupied by the hydrated polymer, and their effective concentration is increased to a level incompatible with solubility. It is less effective in the purification of IgG but is useful for the isolation of the larger IgM. 

Wong and co-workers [22] also applied the methodology in the preparation of a library of neomycin B mimetics (Fig. 6). Two libraries were prepared by a multiple-component condensation of neamine derived aldehyde, f-butyl isocyanide or isocyanoacetic acid methyl ester, CBZ-N amino acids (xl3) and a glycine conjugated polyethylene glycol methyl ether. The products of the reaction were isolated by precipitation. 

Polyethylene glycol having a Mn of 3400 daltons (1.47 mmol) and p-toluene sulfonic acid (0.012 g) were added to a 100-ml flask and heated to 80°C to 90°C for 3 hours at 0.5 to 1.0 torr. The mixmre was cooled and treated with the Step 1 product (1.47 mmol) and 10.0 ml of THF it was further treated with divinyl tri(ethylene glycol) (2.94 mmol) in 10 ml of THF. This reaction mixture was stirred for 2 hours at ambient temperature and then treated with 0.3 ml triethylamine. The reaction mixture was precipitated in 100 ml of hexane, and the product was isolated having aM of 25,000 daltons. 

A reactor was charged with polyethylene glycol (0.5 mol M 10,000), and treated with 50 ml of toluene, and azeotropically dried by refluxing for 2 hours. The resulting mixture was dissolved in 30 ml of THF and treated dropwise with sodium hydride (5 mmol) dissolved in 20 ml of THF and refluxed overnight. This mixture was then treated with ethyl-5-bromovalerate (5 mmol) and refluxed overnight and concentrated. The residue was precipitated by the addition of 2-propanol/diethyl ether, 1 1, and then fdtered to yield 4.5 g of isolated product. 

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