Hydroxyethyl derivatives precipitation

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

Physicochemical studies have also been performed on carboxymethyl-ated 0-methyl- and 0-(2-hydroxyethyl)-cellulose. As with other car-boxymethylated polysaccharides, the degree of substitution and the distribution of substituents play a dominant role in the viscosity of aqueous solutions of O-(carboxymethyl)starch. Viscosimetric "" and other measurements indicate that 0-(carboxymethyl)amylose exists as a random coil in solution, " and that the chains are stiffer than the corresponding cel-lulosic chains whereas the stiffness of the chains of 0-(carboxy-methyl)dextran is little different from that of other charged ether derivatives of dextran and dextran sulfate. Fractional precipitation is a useful procedure for obtaining homogeneous fractions of carboxymethylated polysaccharides, as with other polysaccharide ethers. Acetylated O-(carboxymethyl) cellulose provides a useful basis for the formation of desalination membranes. ... 

A/-ISOpropyl Acrylamid6. Homopolymers from A(-isopropyl acrylamide (NlPAAm) are well known and have been of great interest because of their low critical solution temperature (LOST) behavior in water-solution. The polymer is soluble at low temperatures in water and precipitates above the LOST upon heating. Those kinds of polymers are potentially useful in the pharmaceutical or medical area. The homo- and copolymerization with water-soluble comonomers such as 2-hydroxyethyl methacrylate and characterization of the corresponding polymers of NlPAAm are described in some papers. In the case of copolymerization with hydrophobic comonomers, the use of an organic solvent is necessary, otherwise the polymerization has to be carried out in emulsion. But the different solubilities of the monomers in water often make the copol3unerization of water-soluble and water-insoluble monomers by classical emulsion polymerization difficult. Because of the above discussed property of cyclodextrin derivatives, these problems can be avoided if the copolymerization reactions are performed in the presence of cyclodextrin derivatives. 

---