Patent GB-804117-A (GB)
Title: New lactic acid derivatives and process for the preparation thereof
IPC: C07C69/68
Filed: 1955-12-13
Abstract: The invention comprises poly-lactic acid derivatives of the general formula <FORM:0804117/IV (a)/1> wherein R represents a mono- or poly-valent unsubstituted aliphatic, cycloaliphatic or arylaliphatic residue and n is an integer greater than 1, or R represents a mono- or poly-valent aliphatic, cycloaliphatic or arylaliphatic residue substituted with one or more "inert substituents" and n is an integer, and the preparation thereof by heating lactide with a mono- or polyhydric aliphatic, cycloaliphatic or arylaliphatic alcohol which is unsubstituted or may contain one or more "inert substituents" in the presence of an acid catalyst, at least 2 mols. of lactide being used per mol. of unsubstituted mono- or poly-hydric alcohol and at least 1 mol. of lactide being used per mol. of substituted mono- or poly-hydric alcohol.  By "inert substituents" is meant substituents which do not interfere with the course of the reaction such as halogen, ether, ester, amide and nitrile substituents.  The preferred poly-lactic acid derivatives have the general formula <FORM:0804117/IV (a)/2> wherein R1 represents an unsubstituted aliphatic or arylaliphatic group, e.g. a methyl group, X represents -CN, -CONH2 or -COOR, R being an alcohol residue such as an alkyl group, and n is an integer.  Suitable substituted alcohols for use in the above process are the carboxylic esters, amides and nitriles of hydroxycarboxylic acids such as of lactic, glycollic, citric and mandelic acids, lactic acid ethyl ester, lactyl-lactyl-lactonitrile and bislactic acid glycol ester. Suitable unsubstituted alcohols are ethanol, cyclohexanol, glycol, glycerol, polyglycol 400, pentaerythritol and polyethyleneoxide alcohols.  The lactide reactant may be the racemic or optically active form.  The acid catalyst used in the above process may be sulphuric acid, a toluenesulphonic acid, methanesulphonic acid or phosphoric acid.  The process is preferably carried out using a melt of the lactide reactant, e.g. at a temperature of from 80 DEG  to 180 DEG  C. Alternatively, the process may be carried out in an inert solvent, e.g. benzene, toluene, xylene or chlorobenzene, preferably at a temperature in the range of 80 DEG  to 150 DEG  C., or at the boiling-point of the reaction mixture.  Poly-lactic acid derivatives of the above general formula containing about 6 to 12 lactic acid units are soluble in the cold in chloroform and methylene chloride but in ethanol only in the hot.  Poly-lactic acid derivatives containing more than 12 may be precipitated from their solutions in chloroform or methylene chloride by the addition of methanol.  In the examples: (5) cyclohexyl-(19)-lactyl-) lactate is prepared by heating 1 mol. of lactide and 1/14 mol. of cyclohexanol in the presence of sulphuric acid, the product being a solid insoluble in water but soluble in chloroform; the product may be precipitated from the chloroform solution by adding methanol; (6) (12-lactyl)-lactamide, a solid glass, is prepared by heating 1 mol. of lactide and 1/6 mol. of lactic acid amide in the presence of p-toluenesulphonic acid; (9) bis-(10-lactyl)-glycolates is prepared by heating 1 mol. of lactide and 1/10 mol. of glycol in the presence of sulphuric acid; (10) bis - (20 - lactyl) - glycolester is prepared by heating 1 mol. of lactide and 1/20 mol. of glycol in the presence of sulphuric acid; the product can be drawn into threads in the hot, and in the cold is a solid soluble in chlorform from which solution it may be precipitated by the addition of methanol; (12) tris-(10-lactyl)-glycerol ester is prepared by heating 1 mol. of lactide and 1/15 mol. of glycerol in the presence of sulphuric acid; the product is oily in the hot and solid in the cold; (14) bis-(40-lactyl) glycol ester is prepared from 1 mol. of lactide and 1/40 mol. of glycol in the presence of sulphuric acid; the product is a solid soluble in chloroform from which solution it may be precipitated by the addition of methanol; (15) bis-(80-lactyl)-glycol ester is prepared as in (14) using 1/80 mol. glycol and has the properties indicated in (14); and (16) bis-(12-lactyl)-polyglycol (400)-ester is prepared from 1 mol. of lactide and 1/12 mol. polyglycol (400) in the presence of sulphuric acid; the product is a water-soluble viscous oil.  For examples of poly-lactic acid derivatives of the above general formula where n is less than 4 (see Group IV (b)).ALSO:The invention comprises lactic acid derivatives of the general formula <FORM:0804117/IV (b)/1> wherein R represents a mono- or poly-valent unsubstituted aliphatic, cycloaliphatic or arylaliphatic residue and n is an integer greater than 1, or R represents a mono- or poly-valent aliphatic cycloaliphatic or arylaliphatic residue substituted with one or more "inert substituents" and n is an integer, and the preparation thereof by heating lactide with a mono- or poly-hydric aliphatic, cycloaliphatic or arylaliphatic alcohol which is unsubstituted or may contain one or more "inert substituents" in the presence of an acid catalyst, at least 2 mols. of lactide being used per mol. of unsubstituted mono- or poly-hydric alcohol and at least 1 mol of lactide being used per mol. of substituted. mono- or poly-hydric alcohol.  By "inert substituents" is meant substituents which do not interfere with the course of the reaction such as halogen, ether, ester, amide and nitrile substituents.  The preferred compounds have the general formula <FORM:0804117/IV (b)/2> wherein R1 represents an unsubstituted aliphatic or arylaliphatic group, e.g. a methyl group, X represents -CN, -CONH2 or -COOR, R being on alcohol residue such as an alkyl group, and n is an integer.  Suitable substituted alcohols for use in the above process are the carboxylic esters, amides and nitriles of hydroxycarboxylic acids such as of lactic, glycollic, citric and mandelic acids, lactic acid ethyl ester, lactyllactyllactonitrile and bislactic acid glycol ester. Suitable unsubstituted alcohols are ethanol, cyclohexanol, glycol, glycerol, polyglycol 400, pentaerythritol and polyethyleneoxide alcohols.  The lactide reactant may be the racemic or optically form.  The acid catalyst used in the process may be sulphuric acid, a toluenesulphonic acid, methanesulphonic acid or phosphoric acid.  The process is preferably carried out using a melt of the lactide reactant e.g. at a temperature of from 80 DEG  to 180 DEG  C. Alternatively, the process may be carried out in an inert solvent, e.g. benzene, toluene, xylene or chlorobenzene, preferably at a temperature in the range 80 DEG  to 180 DEG  C. or at the boiling point of the reaction mixture.  In the examples the following compounds are prepared: ethyl lactyllactyllactate, lactyllactylloctonitrile, tetralactyl-lactonitrile, ethyl trilactyllactate, cyclohexyl - (19 - lactyl -) lactate, (12 - lactyl) - lactamide, bis - (dilactyl) - glycolester, bis - tetralactyl) glycolester, bis - (10-lactyl) glycolester, bis - (20 - lactyl) glycolester, tris - (tetra - lactyl) glycerol ester, tris - (10-lactyl) glycerol ester, tetrakis - (tetralactyl) pentaerythritol ester, bis-(40-lactyl) glycolester, bis-80-lactyl) glycol ester, bis-(12-lactyl polyglycol (400) ester, bis-(5-lactyl) glycol ester, p-chloro - cyclohexyl - trilactyllactate, b ,b ,b  - trichloroethyl - (5 - lactyl) lactate, b  - chloroethyl - (5 - lactyl) lactate, (b  - phenoxyethyl)-trilactyllactate, (b  - 2,4,5 - trichlorophenoxyethyl) - trilactyllactate, hexalactyl - butylglycolic acid ester, hexalactyltrimethylcitrate and hexalactyl-ethyl-mandelate.