Patent GB-834227-A (GB)
Title: Poly-n-quaternary ammonium electrolytes and í¡í¡ thereof
IPC: B01J41/14
Filed: 1956-01-20
Abstract: Water - soluble, poly - N - quaternary ammonium electrolytes are formed from proteins or polypeptides containing free amino or carboxyl groups in side chains by directly quaternizing amino groups to form products with at least 6 identical or different quaternary ammonium groups per molecule, or, in the case of starting materials containing free carboxyl groups, by reacting the carboxyl groups, if desired after esterification, either with a diamine containing a primary and a tertiary amine group, the latter then being quaternized, or with a diamine containing a primary amine and a quaternary ammonium group.  Suitable agents for quaternization are alkyl halides, e.g. butyl bromide, lauryl bromide; ethylene iodohydrin; bromoacetamide; a -bromopropane sulphonic acid amide; ethane- or o-toluene-sulphonic acid methyl ester, methane- or benzene-sulphonic acid ethyl ester; dimethyl-, diethyl- or dipropyl sulphate; butane-1,3- or -1,4-sultone. Different alkylating agents can be used successively or simultaneously.  By selecting suitable ones it is possible to introduce acid, ester or salt groups.  The ester groups are subsequently saponified.  Hydrophilic groups, e.g. acid amide, ureido, ureylene, hydroxyl, amino, carboxyl or sulphonic groups or ether or thioether bridges may also be introduced into the molecule.  Groups with a negative charge, e.g. carboxyl or sulphonic acid, should be present in the final product in smaller number than the quaternary nitrogen atoms, and as salts, e.g. carboxylates.  The products may be purified by dissolving, e.g. in methanol, glycol, butane-1,3-diol and precipitating, e.g. by addition of ether, acetone or isopropyl alcohol.  They may be vacuum or freeze dried.  Anions can be exchanged by means of anion exchangers.  The examples relate to treatment of synthetic polypeptides (see Group IV (a)).  The products are useful in pharmacy.ALSO:Water-soluble poly-N-quaternary ammonium electrolytes are formed from synthetic polypeptides, containing free amino or carboxyl groups in side chains, by directly quatenizing amino groups to form products with at least 6 identical or different quaternary ammonium groups per molecule or, in the case of polypeptides having free carboxyl groups, by reacting the carboxyl groups, if desired after esterification, either with a diamine containing a primary and a tertiary amine group the latter then being quaternized, or with a diamine containing a primary amine and a quaternary ammonium group.  Suitable quaternizing agents are alkyl halides, e.g. butyl or lauryl bromide; ethylene iodohydrin; bromoacetamide; a -bromopropane sulphonic acid amide; ethane- or o-toluene-sulphonic acid methyl ester, methane-or benzene-sulphonic acid ethyl ester; dimethyl-diethyl or dipropyl sulphate; butane-1,3- or -1,4-sultone.  Different alkylating agents can be used successively or simultaneously.  By selecting suitable ones it is possible to introduce acid, ester or salt groups.  The ester groups are subsequently saponified.  Hydrophilic groups, e.g. acid amide, ureido, ureylene, hydroxyl, amino, carboxylic or sulphonic groups or ether or thioether bridges may also be introduced into the molecule. Groups with a negative charge, e.g. carboxyl or sulphonic acid, should be present in the final product in smaller number than the quaternary nitrogen atoms, and as salts, e.g. carboxylates.  The products may be purified by solution, e.g. in methanol, glycol, butane-1,3-diol followed by precipitation, e.g. with ether, acetone or isopropyl alcohol.  They may be vacuum or freeze dried.  Anions can be exchanged by means of anion exchangers.  In examples: (1) polylysine hydrochloride is reacted with dimethyl sulphate in presence of sodium carbonate; (2) polyglutamic acid-g -methyl ester is heated with N,N-dimethyl propylene diamine.  The product is heated with a solution of propane sultone in dimethyl formamide and then with dimethyl sulphate.  Unreacted ester groups are saponified; (3) a co-polypeptide is formed from l-glutamic acid-g -methyl ester N-carboxy anhydride and glycine - N - carboxy anhydride, and is heated with N,N-dimethyl propylene diamine and then with dimethyl sulphate; (4) a co-polypeptide is formed from "N" - carbobenzyloxy - l - lysine - N - carboxy anhydride and l-alanine-N-carboxy anhydride, the carbobenzyloxy group is split off and the product reacted with dimethyl sulphate; (5) a -polyglutamic acid dimethylaminopropylamide is heated with chloroacetic acid methyl ester and then with dimethyl sulphate; (6) a copolypeptide is prepared from l-glutamic acid-d -methyl ester-N-carboxy anhydride, glycine-N-carbomyanhydride and l-leucine-N-carboxyanhydride and is heated with N,N-dimethyl propylene diamine and then with dimethyl sulphate.  The products are useful in pharmacy.