PREPARATION FROM LACTIC ACID, ACETIC ACID, AND METHANOL

E. M . F IL A C H IO N E

C. H . F IS H E R

The conversion o f lactic acid into m ethyl a-acetoxypro- pionatc w ithout the use o f acetic anhydride, ketene, or acetyl chloride is described. Acetoxypropionic acid is formed satisfactorily when lactic acid, acetic acid, an entraining agent such as benzene, and an esterification catalyst such as sulfuric acid, are refluxed so that water is removed. Acetoxypropionic acid is transform ed into its m ethyl ester by treatm ent with either m ethanol or

I

it has now become desirable to have efficient and low -cost methods for preparing this diester from lactic acid. An attractive con­

tinuous method {4), which comprised the conversion o f lactic acid into methyl lactate followed b y acetylation with acetic anhydride or ketene, was described recently; but this method requires either acetic anhydride or ketene, which are more expensive than acetic acid. The use o f acetic acid as the acetylat- ing agent would have the advantages o f lowering the cost of methyl acetoxypropionate (assuming comparable yields) and eliminating the need o f plant facilities to convert acetic acid into acetic anhydride or ketene. T h e desirability o f using acetic acid as the acetylating agent is increased b y the fact that acetic acid as well as m ethyl acrylate is produced b y the pyrolysis of methyl acetoxypropionate:

CH,COOCH(CH,)COOCH, 500° c - CH.COOH - f

(I) CH»: CHCOOCH, (1)

m ethyl acetate. T h e best means for esterifying acetoxy­

propionic acid consists in passing this acid and m ethanol vapor countercurrently through a packpd tower m ain­

tained at 70° to 130° C. T h e m anufacture o f m ethyl or- acetoxypropionate by this m ethod would be particularly advantageous under wartim e conditions as it would not require the construction o f plants to convert acetic acid into acetic anhydride or ketene.

A t least tw o approaches to the problem of preparing m ethyl acetoxypropionate with acetic acid as the acetylating agent can be followed. B y the first, m ethyl lactate is prepared b y esteri­

fication of lactic acid, and the methyl lactate is acetylated with acetic acid. The second approach comprises the acetylation of lactic acid with acetic acid, followed by esterification o f the acetoxypropionic acid (II). Preliminary experiments showed that, although some o f the desired diester (I) is obtained, methyL acetate is formed readily when m ethyl lactate is treated with acetic acid. Since this side reaction cannot occur when lactic acid is acetylated, the possibility o f transforming lactic acid into methyl acetoxypropionate b y the second route (Equations 2 and 3) was investigated:

CH.COOH + HOCH(CH,)COOH — ►

CH,COOCH(CH,)COOH + H ,0 (2>

(II)

CH.COOCH (CH.)COOH + CH.OH —

»-(II)

CHiCOOCH(CH,)COOCHi

I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y 473 acetylate lactic acid with acetic acid have been described.

R E A C T I O N O F A C E T I C A C ID W I T H L A C T IC A C ID acetoxypropionic acid. T h e alcoholic hydroxyl group also reacts with the lactic acid carboxyl group, forming lactyllactic acid (where x = 2) and similar linear condensation products react with acetic acid in tw o ways. The acetic acid m ay acetylate the terminal alcoholic hydroxyl group, or it m ay decrease the chain length of the linear condensation products by acidolysis.

Since all the reactions with acetic acid lead to the formation of acetoxypropionic acid, it would be expected that an excess of acetic acid would be helpful. Experience has borne out this expectation.

A commercial, edible grade of 8 0 % lactic acid, which was almost colorless, was used in m ost o f the acetylation experiments.

T h e lactic acid was acetylated by refluxing a mixture of lactic reaction was considered com plete when approximately one mole o f water had been rem oved for each mole of lactic acid in the reaction mixture. A fter the mineral acid had been neutralized with anhydrous sodium acetate (usually 4 grams o f sodium acetate per ml. o f sulfuric acid), the acetoxypropionic acid was distilled under reduced pressure.

The results o f the acetylation experiments show that acetoxy­

propionic acid can be made satisfactorily and in high yields by the reaction of acetic acid with lactic acid. T h e amount of lactic acid converted into acetoxypropionic acid varied with the amount of acetic acid used. The yield of acetoxypropionic acid was approximately 8 0 % when a considerable excess o f acetic acid was used (Table I). The dependence o f yield upon the ratio o f acetic acid to lactic acid is shown in Figure 1. The brown, viscous distillation residues, which probably consist mainly o f acetylated condensation products of lactic acid, should be useful as a starting material in making monomeric lactic acid, methyl lactate, or acetoxypropionic acid.

Since both acetic and lactic acids are inexpensive and p o­

tentially available in large quantities, acetoxypropionic acid could be made on a large scale at low cost. As ordinarily pre­

pared, this acid is a m oderately viscous fluid that supercools easily and is difficult to crystallize unless seeded. When crystal­

lized, the acid is a low-melting solid (2). It distills at 75° C. o f 3 grams of sodium acetate the mixture was distilled. T h e yield o f acetoxypropionic acid was 2 6 % . The results o f this experi­

ment indicate that the esterification of the alcoholic hydroxyl group is more rapid than the acidolysis o f the ester group.

R E A C T I O N O F A C E T O X Y P R O P I O N I C A C ID W I T H M E T H Y L A C E T A T E

Because of the high vapor pressure of m ethyl acetate, the reaction of m ethyl acetate with acetoxypropionic acid was studied in a closed system. A mixture of acetoxypropionic acid,

474 I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y Vol. 36, No. 5 sulfuric acid, and the products were isolated by distillation under reduced pressure.

The highest yield of methyl acetoxypropionate obtained by the reaction of acetoxypropionic acid with methyl acetate was 8 4 % (Table II). Acetic acid also was isolated. The most extreme experimental conditions used (140° to 150° C. for 4 hours) were not drastic. This reaction, which does not require arctic anhydride or ketene, could be employed to prepare methyl acetoxypropionate.

E S T E R I F I C A T I O N O F A C E T O X Y P R O P I O N I C A C ID A N D M E T H A N O L

Because o f the importance of the reaction, the estérification o f acetoxypropionic acid and methanol was studied extensively under various conditions. In some of the experiments, mixtures of /the tw o reactants were heated in the liquid phase and then distilled to determine the nature and amounts of the products.

In other experiments the estérification was effected by passing methanol vapor and acetoxypropionic acid countercurrently through a packed tower under atmospheric or reduced pressures.

The liquid-phase estérifications were carried out b y refluxing a mixture o f 0.5 mole o f acetoxypropionic acid, 2.5 moles of methanol, and 0.5 ml. of sulfuric acid. A t the end of the reaction period the sulfuric acid was neutralized with sodium acetate

propionate were not obtained because of the formation of methyl

Ta b l e I I I . Me t h y l La c t a t e a n d Ac e t o x y p r o p i o n a t e Pr o d u c e d acetoxypropionate, methyl lactate, and methyl acetate were 34, 43, and 3 6 % after 1 hour of refluxing, and 21, 52, and 4 8%

after 3 hours. In both instances the com bined yields o f the lactic esters were more than 7 0 % . Probably the distillation residues contained polylactic acid (III) or esters of polylactic acid, which should be o f some value as a source of monomeric lactic acid, methyl lactate, or acetoxypropionic acid.

Much higher yields were obtained when the estérification was carried out with methanol vapor in a packed tower under non­

equilibrium conditions. Slightly different techniques were used at atmospheric and at 100 mm. pressure.

Under a pressure o f approximately 100 mm., a mixture o f acetoxypropionic acid, methanol, and sulfuric acid was added dropwise into the top o f a Pyrex tower (1 X 48 inches) packed with ’ /(-in ch porcelain Berl saddles and was electrically heated.

The temperature of the column was controlled and recorded automatically. Methanol was passed into a heated vaporizing flask, and the vapor issuing from this flask was passed into the bottom o f the packed tower. The methanol vapor was passed through the tower as long as acetoxypropionic acid was being passed into the column and until the dry appearance of the packing indicated that all the acetoxypropionic acid had reacted.

The vapors withdrawn from the top o f the tower, which con­

sisted of methanol, methyl acetoxypropionate, and other volatile products, were passed into the center of a steam-jacketed dis­

tillation column packed with small Berl saddles. The methanol and water vapors that passed through this stripping still were condensed. The products of higher boiling points, which were collected at the bottom o f the distilling column, were redistilled in a vacuum to determine the amounts' of methyl lactate and methyl acetoxypropionate obtained. Yields o f methyl acet­

oxypropionate as high as 7 2 -7 5 % were obtained at temperatures of 8 0 °-1 0 0 ° C. M ethyl lactate also was produced (Table I II).

When acetoxypropionic acid was esterified with methanol vapor in the packed tower under atmospheric pressure, the pro­

cedure was slightly modified. As before, methanol vapor and acetoxypropionic acid were passed countercurrently through the tower, and the vapors withdrawn from the top of the tower were passed into the center of the steam-jacketed distilling column. The methanol distilling from the top of the column was condensed and returned through a liquid seal to the heated vaporizing flask. When the estérification was carried out at temperatures below 108° C., the material collected at the bottom o f the distilling column contained water and some methyl lactate and methyl acetoxypropionate, but most of the esters passed downward through the estérification tower and were collected in a flask at the base. The contents o f the flasks located at the bottom of both the distillation and estérification columns were distilled under reduced pressure to determine the yields of methyl lactate and methyl acetoxypropionate (Table III).

When estérification was carried out in the packed tower under atmospheric pressure and at tempera­

tures above approximately 108° C., the methanol vapor was recycled and passed through the tower until it appeared that all the acetoxypropionic acid had reacted and passed as ester through the top of the tower into the distilling column. The material collected at the b ottom o f the column was then distilled to separate the products.

The data in Table II I show that m oderately high yields of methyl acetoxypropionate were obtained b y the methanol vapor method, both under atmospheric and reduced pressures. M ost of the com bined yields o f m ethyl acetoxypropionate and m ethyl lactate ranged from 80 to 9 0% . The combined yields were moderately high even in the absence o f an estérifica­

tion catalyst (experiments 311 and 312).

May, 1944

D IS C U S S IO N O F R E S U L T S

The production of methyl acetoxypropionate from lactic acid, acetic acid, and methanol by the methods described here have the advantage of not requiring the use of acetic anhydride or ketene, but the yields are not so high as those obtained b y con­

version o f lactic acid into methyl lactate followed by acétylation

•with acetic anhydride, as described in the preceding paper. T o . afford a comparison of the relative merits of the two methods, the materials costs o f methyl acetoxypropionate prepared b y the two methods were calculated. The prices assumed for the inter­

mediate chemicals m ay not have been exactly correct, but the same prices were used for both methods and therefore the cal­

culated material costs should be adequate for a preliminary comparison. In making the calculations, the cost of sulfuric acid used as catalyst was not included, and it was assumed that an over-all yield of 8 5 % acetoxypropionic acid could be obtained from lactic acid b y treatment of the distillation residues with acetic acid. The other yields assumed in estimating relative costs were: 7 5 % methyl acetoxypropionate and 10% methyl lactate in the estérification of acetoxypropionic acid, 90 % methyl lactate in the estérification o f lactic acid, and 96 % methyl acetoxypropionate in the acétylation of methyl lactate.

All yields were calculated on the basis of unrecovered starting materials.

The calculated cost o f materials indicated that the acetoxy­

propionic acid method of making methyl acetoxypropionate is somewhat more expensive (approximately 2 cents per pound) than the previously described methyl lactate method (4). The acetoxypropionic acid method, however, has the advantage of not requiring plants for the manufacture of acetic anhydride or ketene. Owing to the shortage of alloys and other construction materials, this advantage would be highly important under war­

time conditions if large quantities o f methyl acrylate were manu­

factured by the pyrolysis of methyl acetoxypropionate.

A C K N O W L E D G M E N T

The assistance and cooperation of other members of the Carbohydrate Division o f this laboratory are gratefully acknowl­

edged.

L I T E R A T U R E C I T E D

(1) Anschiltz, R ., and Bertram, W ., Ber., 37, 3971-4 (1904).

(2) Auger, M . V ., Compt. rend., 140, 938 (1905).

(3) Burns, R ., Jones, D . T ., and R itchie, P. D ., J. Chem. Soc., 1935, 400-6.

(4) Filachione, E. M ., Fein, M . L ., Fisher, C. H ., and Smith, L. T ., D iv. Ind. Eng. Chem ., A.C .S., D etroit, April, 1943.

(5) Fisher, C . H ., R atchford, W . P ., and Smith, L. T ., In d. En q. Chem., 36, 229-34 (1944).

(6) Freudenberg, K „ and M arkert, L „ Ber., 60B, 2447-58 (1927).

(7) Neher, H . T ., In d. En o. Chem ., 28, 267-71 (1936).

(8) R itchie, P . D ., Jones, D . T ., and Burns, R ., U. S. Patent 2,265,814 (D ec. 9, 1941).

(9) R ohm , O., Ibid., 1,121,134 (D ec. 15, 1914).

(10) R ohm , O., and Bauer, W ., German Patent 693,140 (June 6, 1940).

(11) Smith, L. T ., Fisher, C . H ., Filachione, E. M ., R atchford, W . P ., and Fein, M . L ., D iv . Org. Chem ., A .C .S., M emphis, April 1942.

(12) Smith, L. T ., Fisher? CTH ., R atchford, W . P ., and Fein, M . L., In d. En o. Chem., 34, 473-9 (1942).

(13) Starkweather, H . W ., and Collins, A. M ., U . S. P atent 2,218,362 (O ct. 15, 1940).

(14) W atson, P. D „ In d. En o. Chem ., 32, 399-401 (1940).

(15) W in gfoot Corp., Brit. P atent 522,981 (July 2, 1940).

Pr e s e n t e das pa rt o f th e S y m p osiu m on L a ctio A cid and D e riv e d P rod u cts b efore th e D iv isio n o f In du strial and E n gin eerin g C h em istry a t the 106th M eetin g o f th e Am e r i c a n Ch e m i c a l So c i e t y, P ittsb u rgh , Pa.