Patent GB-793555-A (GB)
Title: A process for the preparation of macrocyclic lactones
IPC: C11B9/00
Filed: 1955-06-28
Abstract: Macrocyclic lactones, i.e. cyclic esters of hydroxy carboxylic acids, in which the two functional groups are separated by a chain of 10 to 20 carbon atoms, which may be alternated by hetero atoms, are prepared by depolymerizing a polymer of a hydroxy carboxylic acid or a mixed polymer of a hydroxy carboxylic acid and an alcoholic component by heating, preferably in vacuo, in the presence of a trans-esterification catalyst and a high-boiling component which is not, or substantially not, miscible with the macrocyclic lactone formed and which removes this lactone from the reaction mixture by co-distillation at the rate at which it is formed.  Suitable catalysts are the hydroxides, oxides, carbonates, alcoholates, glycerolates and alkaline salts, preferably carboxylic acid salts, of alkali and alkaline earth metals.  Trivalent alcohols such as glycerol and pentane triol-1,2,5 may be used as co-distillation components and may also form the alcohol components of the copolymers.  The polymer or copolymers of the hydroxy carboxylic acid may be prepared by esterification of the hydroxy acid, or the hydroxy acid together with the alcoholic component, in the presence of an esterification catalyst and of an inert solvent which forms an azeotrope with water, or boils sufficiently high to ensure continuous removal of water, the reaction water formed being distilled off continuously with the solvent.  A trans-esterification catalyst is then added, which may in addition neutralize the esterification catalyst present, the solvent is distilled off and a co-distillation component such as glycerol is added, and finally the product is heated to depolymerize the polymer, preferably in vacuo.  The polymerization and depolymerization may also be effected without interruption in the same apparatus.  Thus the hydroxy acid may be heated in the presence of a trans-esterification catalyst, e.g. potassium hydroxide, and a co-distillation component, preferably in vacuo, until the polymerization is completed and the reaction water formed has been removed, and the heating is then continued without interruption until the desired macrocyclic lactone is formed by depolymerization.  The product may be freed from impurities by fractional distillation.  In examples: (1) 15-hydroxy-11-oxa-hexadecanoic acid is polymerized by heating in the presence of toluene sulphonic acid and cumene, sodium methylate and glycerol are then added, the cumene is distilled off, and the polymer is heated under vacuum whereby 12-oxa-hexadecanolide co-distils with the glycerol; (2) the polymerization of 15-hydroxy-11-oxa-hexadecanoic acid is effected in the presence of glycerol and potassium hydroxide solution under vacuum and the depolymerization of the product to 12-oxa-hexadecanolide is then carried out under higher vacuum; (3) 14-hydroxy-11-oxa-pentadecanoic acid is converted to 12-oxa-pentadecanolide in accordance with (1); (4) 14-hydroxy-pentadecanoic acid is converted to pentadecanolide in accordance with (2); (5) 14-hydroxy-pentadecanoic acid is converted to pentadecanolide as in (1); (6) 1,4-hydroxypentadecanoic acid is polymerized with glycerol, toluene sulphonic acid and xylene, sodium methylate and glycerol are added and depolymerization is effected under vacuum; (7) pentadecanolide is obtained using glycerol containing dissolved lithium in accordance with (2) or (4); (8) the polymer of 11-hydroxy-pentadecanoic acid is prepared according to (3), a solution of calcium in glycerol is added and depolymerization is effected whereby pentadecanolide co-distils with glycerol; (9) the process is repeated using glycerol and potassium 14-hydroxy-tetradecane carboxylate; (10) 14-hydroxy-pentadecanoic acid is polymerized according to (1), a solution of sodium methylate in pentane-triol-1,2,5 is added, cumene is distilled off and the cylisation is effected as in (1).  The products are valuable oderiferous substances.  Specifications 433,632, 440,416, 471,914 and 490,044, [all in Group IV], are referred to.ALSO:Polymers of hydroxycarboxylic acids in which the two functional groups are separated by a chain of 10 to 20 carbon atoms, or mixed polymers of such a hydroxy acid with an alcoholic component, may be prepared by esterification of the hydroxy acid, or the hydroxy acid together with the alcoholic component, in the presence of an esterification catalyst and of an inert solvent which forms an azeotrope with water or boils sufficiently high to ensure continuous removal of water, the reaction water formed being distilled off continuously with the solvent.  The polymerization may also be effected by heating the hydroxy acid in the presence of a catalyst of the type used for transesterification reactions and a polyhydric alcohol, preferably in vacuo, until the polymerization is completed.  Suitable alcoholic components are glycerol and pentane-triol-1,2,5.  Suitable transesterification catalysts are the hydroxides, oxides, carbonates, alcoholates, glycerolates and alkaline salts of alkali and alkaline earth metals.  The polymers and copolymers so obtained may be depolymerized and cyclized to form macrocyclic lactones (see Group IV (b)).  In examples: (1) 15-hydroxy-11-oxa-hexadecanoic acid is polymerized by heating in the presence of toluene sulphonic acid and cumene, water being distilled off with cumene; (2) 15-hydroxy-11-oxa-hexadecanoic acid is heated under vacuum with glycerol and potassium hydroxide solution; (3) 14-hydroxy-11-oxapentadecanoic acid is polymerized as in (1); (4) 14-hydroxy-pentadecanoic acid is polymerized with glycerol and potassium hydroxide according to (2); (5) 14-hydroxy-pentadecanoic acid is polymerized by boiling in the presence of toluene sulphonic acid and cumene; (6) 14-hydroxypentadecanoic acid and glycerol are polymerized by boiling in the presence of toluene sulphonic acid and xylene; (7) 14-hydroxy-pentadecanoic acid is polymerized with glycerol in which lithium has been dissolved according to (2) or (4); (8) the polymer of 14-hydroxypentadecanoic acid is prepared according to (3); (9) 14-hydroxy-pentadecanoic acid is converted into a polymer with glycerol and potassium 14-hydroxy-tetradecane-1-carboxylate according to (2) or (4).  Specifications 433,632, 440,416, 471,914 and 490,044, [all in Group IV], are referred to.