UNITED STATES PATENT OFFICE 2,55,779 HALOGENATED DERWATWES of AFL PATIC ACDS and METHOD of AKING SAE Edgar C

Patented June 19, 1951 2,557,779

UNITED STATES PATENT OFFICE 2,55,779 HALOGENATED DERWATWES OF AFL PATIC ACDS AND METHOD OF AKING SAE Edgar C. Britton and John C. Wander Weele, Mid and, Rich, and John E. Livak, Union, S. C., assignors to The Dow Chemical Company, Mid and, lich., a corporation of Delaware

No Drawing. Original application November , 946, Seria No. 08,62. Divided and this ap plication September 25, 1947, Serial No. 6,150 Cains. (C. 269-539) 2 This invention concerns certain new halogen mole of the lactone reactant in order to obtain containing derivatives of Saturated aliphatic halogenation at a rapid rate. The halogenation monocarboxylic acids having at least 4 carbon is usually carried out at temperatures in the Order atoms in a carbon chain of the acyl radical and of from 80° to 150° C., but it may be accomplished a method of making the derivatives. It per 5 at lower, or somewhat higher, temperatures if de tains especially to alpha-halolactones of the sired. The halogen apparently adds directly to gamma-hydroxy-aliphatic carboxylic acids and the molecule of the lactone with formation of the preparation of Such halolactones. an alpha-gamma-dihalo-aliphatic carboxylic We have found that halogens, e. g. fluorine, acid. Only a minor amount of hydrogen halide bromine, or bromochloride, etc., may be reacted O is eWOWed. directly with a lactOne of a ganna-hydroxy-ali The alpha - gamma, - dihalo - carboxylic acids phatic monocarboxylic acid having 4 or more thus produced are thermally unstable compounds carbon atoms in a chain of the acy radical which undergo dehydrohalogenation and lactOne to form a corresponding alpha-ganna-dihalo formation at temperatures below their boiling aliphatic carboxylic acid which is therinally 5 temperatures at atmospheric preSSure. In Some unstable and may be dehydrohalogenated by instances, they may be distilled under vacuum to heating to produce an alpha - halo -lactone of collect a Substantial portion thereof in undecom the gamma-hydroxy carboxylic acid as an ulti posed form. The alpha-ganna-dihalor-carbox mate product. The alpha-haio-ganna-lactOnes ylic acids may be esterified by reaction with alco thus produced are USeful as chemical agentS 20 hols Such as methyl, ethyl, or propyl alcohol, etc., for the preparation of a wide variety of more the esters may readily be separated and purified, Complex derivatives of the aliphatic carboxylic e. g. by distillation. The alpha-gamma-dihalo acid. They are particularly useful as inter alphatic monocarboxylic acids are new con mediate agents in a method for the production pounds which are useful as chemical agents in of methionine and itS homologues. forming a wide variety of more complex deriva Any lactOne of a Saturated gamma-hydroxy tives of the aliphatic carboxylic acids parent aliphatic monocarboxylic acid may be used as a thereto. For instance, One or both of the halogen Starting material in the process. Examples of atoms thereof Inay be dispiaced by reaction of Such Starting materials are the lactones of Such compound, or an ester thereof, with an alkali gamma-hydroxy-butyric acid, gamma-hydroxy Salt of a carboxylic acid so as to form a complex Valeric acid, gamma-hydroxy-isovaleric acid, polyester. The alpha-gamma-dihalo-carboxylic gamma-hydroxy-caproic acid, etc. The lactone acids have the general formula: of gamma-hydroxy-butyric acid is readily avail able as a by-product from the destructive distill lation of Wood, and the alpha-halo derivatives of 35 a. this lactone are useful as intermediates in the Wherein each X represents a halogen atom, e. g. Synthesis of methionine itself. For these reasons chlorine or bromine, and R represents hydrogen the lactOne of gamma-hydroxy-butyric acid is a or an alkyl radical. preferred Starting material. An alpha-gamma-dihalo-aliphatic carboxylic The lactones may be halogenated by passing a 40 acid prepared as described above is readily de halogen, e. g. chlorine or broiline, into the Sane hydrohalogenated to for in a corresponding alpha While heating the mixture at a temperature Sufi halo-gamma, lactOne by heating the same to cient to cause fairly rapid reaction. The halo a temperature at Which hydrogen halide is genation occurs most readily and rapidly when evolved. The dehydrohalogenation action usual carried out in the presence of a substance capable ly Occurs rapidly upon heating the dihalo com of forming an addition compound with an acyl pound at temperatures in the order of from 100° halide, e. g. acetyl chloride. Examples of Sub to 150° C. at Sub-atmospheric pressure. Higher Stances having this property and useful as cata temperatures may in Some instances be required, lysts for the halogenation are phosphorus tri particularly when the decomposition is carried Chloride, phosphorus pentachioride, phosphorus 50 out at atmospheric pressure. The alpha-halo tribromide, aluminum chloride, ferric chloride, lactOne product is readily purified by distillation. etc. The phosphorus halides are particularly The following examples described certain Ways effective for the purpose and are preferred. Only in Which the invention has been practiced, but a minor amount, e. g. 0.02 molecular equivalent, are not to be construed as limiting the scope of or less, of a phosphorus halide is required per 55 the invention, 2,557,779 3 4. Eacample 1 7 millimeters absolute pressure. It has a den sity at 25° C. of 1.595 and an index of refraction, A solution of 71 grams of phosphorus tribro 12D25, of 1.4905. The yield thereof was approxi mide and 1120 grams of gamma-butyrolactOne mately 71 per cent of theoretical, based on the was heated to a temperature of 100° C., and 1975 amount of valerolactone consumed in the initial grams of bromine were added gradually and with bromination reaction. stirring. The bromine was added at a rate of This application is a division of our Copending about 1 gram per second over a period of about application, Serial No. 708,462, filed November 2.5 hours, after which the late of bromine addi 7, 1946, now patent No. 2,530,348. tion was reduced Somewhat in order to avoid 10 Other modes of applying the principle of the Vaporization of free bromine from the mixture. invention may be employed instead of those ex Considerable heat was evolved during the bro plained, change being made as regards the mination reaction. Which was carried out for the method or compounds herein disclosed, provided most part at temperatures of between 120° and the steps or compounds stated by any of the fol 130° C. After adding the bromine, the mixture 5 lowing claims or the equivalent of such steps or was heated at 130° C. for a period of 4 hours in compounds be employed. order to assure substantial completion of the re We therefore particularly point out and dis action. The Crude brominated product weighed tinctly claim as our invention: 3100 grams and consisted for the most part of 1. The method which comprises reacting an alpha-gamma-dibromo-butyric acid. The yield 20 elemental halogen of the class consisting of chlo of the crude acid was approximately 98 per cent rine and bionine With a lactone of a gamma of theoretical, The alpha-gamma-dibromo hydroxy-aliphatic monocarboxylic acid by pass. butyric acid was heated under vacuum, first to ing the halogen into the lactone while heating evolve the hydrogen bromide formed by thermal the inixture at a reaction temperature below the decomposition of the dibromo-butyric acid, and 25 deconposition tenperature of the alpha, gamma thereafter to distill the resultant alpha-brono dihalo-carboxylic acid reaction product. butyrolactone product. The alpha-bromo-gam 2. The method which comprises forming an ma-butyrolactone is a colorless liquid which boils aliphatic alpha, gamma-dihalo-monocarboxylic at from 94° to 106° C. at 1 millimeter absolute acid by reacting an elemental halogen of the class pressure, has a density at 25° C. of 1.79, and has 30 consisting of chlorine and bromine With a lac an index of refraction, n25, of 1.509. The yield of tone of a gamma-hydroxy-aliphatic monocar alpha-bromo-gamma-butyrolactone was 85 per boxylic acid at about atmospheric pressure and cent of theoretical, based on the gamma, butyr a reaction temperature between 80° and 150° C. olactOne Starting material. 3. The method which comprises forming an Eacample 2 35 aliphatic alpha, gamma-dihalo-monocarboxylic acid by passing an elemental halogen of the class By procedure Similar to that described in EX consisting of chlorine and bromine into a solu ample 1, chlorine was reacted with butyrolactone tion of a major amount of a lactone of a gamma in the presence of phospholus trichloride as a hydroxy-aliphatic monocarboxylic acid and a catalyst to form alpha-gamma-dichloro-butyric 40 catalytic amount of a substance capable of form acid, and the latter was subjected to distillation ing an addition compound With acetyl chloride under Vacuum. In this instance, a portion of while heating the mixture at about atmospheric the dihalo-butyric acid was decomposed to form pressure to a reaction temperature between 30° alpha-chloro-butyrolactone, which was collected and 150° C. as a fraction of distillate, and another portion 4. The method which comprises forming an distilled Without decomposition and was recov aiiphatic aliha, ganna-dihalo-imonocarboxylic ered as the purified compound. The alpha acid by paSSing an elemental halogen of the class gamma-dichloro--butyric acid is a colorleSS liquid consisting of chlorine and bromine into a solution which distilis at temperatures of from 112° to of a major amount of a lactone of a gamma-hy 14 C. at 4 millinineters absolute pressure, has a 50 d'OXy-aliphatic monocarboxylic acid and a cata density at 25° C. of 1.404, and has an index of re lytic amount of a phosphorus halide While heat fraction, 2D25, of 1.477. The alpha-chloro-gam ing the mixture at about atmospheric pressure to ma-butyrolactOne is also a colorleSS liquid. It a reaction temperature between 80° and 150° C. distills at 98 to 100° C. at 4 millimeter's abso 5. The method which comprises forming al lute pressure, has a density at 25° C. of 1.361, and pha, gain ma-dibronobutyric acid by passing bro mine into a Solution of a major amount of the has an index of refraction, nD25, of 1.469. lactone of gamma-hydroxy-butyric acid and a Eacample 3 catalytic amount of a phosphorus bromide while heating the mixture at about atmospheric pres Approximately 192 grams of bromine was added 00 Sure to a reaction tenperature between 80° and in dropwise imanner and With Stirring to a solu 150° C. tion of 1 cubic centimeter of phosphorus tribro 6. The method which comprises forming al mide in 25 grams of ganna-ValerolactOne While pha, gamma-dichlorobutyric acid by passing chlo heating the mixture at temperatures of from 95° rine into a Solution of a major amount of the lac to 100° C. The bromine was added over a period tone of gamma-hydroxy-butyric acid and a cata of 3 hours, after which heating of the mixture lytic amount of a phorphorus chloride while at the temperatures just mentioned was contin heating the mixture at about atmospheric pres ued for another 3 hours. The alpha-gamma Sure to a reaction teiperature between 30° and dibromo-valeric acid, thus formed, Was heated 150° C. under vacuum, first to evolve hydrogen bronide 70 7. The method which comprises forming al formed due to thernal decomposition of the pha, gamma-dibromoValeric acid by passing bro sare, and thereafter to distill the alpha-bromo mine into a Solution of a major amount of the gamma-valerolactone product. The alpha lactone of gar::ma-hydroxy Valeric acid and a bromo-gamma-valerolactone is a colorleSS liquid catalytic amount of a phosphorus bromide while which boils at approximately 120° to 125° C. at 75 heating the mixture at about atmospheric pres

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