Acids of

Many Uses gents, and medicines. More attention is being given, consequently, to the de- velopment of practical methods for ob- taining them from dextrose. From Corn Processes for the fermentation of dextrose to citric, gluconic, 2-keto- C L. Mehltretter giuconic, 5-ketogluconic, a-kctoglu- taric, and itaconic, and similar acids have been developed in the laboratories of the Department of Agriculture. Some, particularly those for citric and Most of the commercial sugar acids gluconic acids, have achieved commer- come from dextrose, the sugar derived cial importance. The large-scale pro- from corn. They are cheap and mild duction of itaconic acid appears and, chemically, maids-of-all-work. promising. Lactic acid, a widely used Their uses range from the simple proc- food acid, is being produced in large ess of cleaning milk cans and bottles volumes by the corn-products indus- to the complex production of vitamins. tries by fermentation of cornstarch Veterinarians and farmers know hyclrolyzates. best the calcium salt of gluconic acid, The acids I have mentioned have which they use for the treatment of also been made by nonfermentative milk fever in cows and which doctors methods, but of the purely chemical sometimes recommend for bee stings. processes only those for obtaining glu- The housewife is most familiar with conic and itaconic acids merit con- cream of tartar, an ingredient of the sideration from a practical standpoint. baking powder she uses for her pies and Some years ago workers at the National cakes. Citric acid, the acid that gives Bureau of Standards devised a proce- the tang to citrus fruit?, she also uses dure for the electrolytic oxidation of for flavoring lemon pies. Its magne- corn sugar to gluconic acid. It appears sium salt—citrate of magnesia—has to be competitive with the fermenta- often been prescribed as a laxative for tion method. The electrolysis is carried her family. No doubt she is also ac- out between carbon electrodes in the quainted with ascorbic acid, the sugar presence of bromides and calcium acid that is made in chemical factories carbonate buíTer, and the gluconic acid and is the same as the vitamin C in is neutralized as it is formed to give oranges and lemons. calcium gluconate. Chemists have known about the Itaconic acid was originally pro- sugar acids for a long time, but new duced in pilot-plant quantities from uses for them are being discovered con- citric acid. The dehydration of citric stantly. For instance, doctors recently acid with mineral acids yields aconitic learned that glucuronic acid, first iso- acid, which is readily decarboxylated to lated from the body in 1875, may re- itaconic acid. More recently, however, lieve the pains of rheumatism and chemists at the Southern Regional Re- sciatica. search Laboratory have demonstrated The versatile nature of the sugar that the calcium magnesium aconitate acids has aroused increasing interest in present in sugarcane molasses can be them as raw materials for the produc- recovered in commercial amounts tion of such things as plastics, deter- without significantly altering the proc- 780 ACIDS OF MANY USES FROIVI CORN 781 cssing of the molasses for sugar pro- tion, processes were devised to recover duction. A practical method was also the residual tartrates in domestic grajee devised for converting the crude pomace and in brandy-still slop. These alkaline-earth aconitate to itaconic significant developments were achieved acid of high purity. It has been esti- by chemists in commercial wineries and mated that at least 4 million pounds of at the Western Regional Research Lab- aconitic acid a year are potentially oratory. At the Atlas Powder Com- available as a byproduct of the sugar- pany, pilot-plant experiments had also cane grown and milled in Louisiana been carried out for the production of and Florida alone. In 1950 there was a tartaric acid by the nitric acid oxida- demand for at least a million pounds tion of dextrose. Still another method of aconitic acid for conversion to esters of synthesis is the catalytic oxidation of for piasticizers. The remaining 3 mil- 5-ketogluconic acid by oxygen. The lion pounds of potential production raw material for this process, calcium would yield about 2 million ]:>ounds of 5-ketogluconate, can readily be pro- itaconic acid for use in the manufac- duced by a biological ]3roc(\ss devel- ture of plastics, detergents and such. oped in the Department of Agriculture. The sugar acids—levulinic, tartaric, Because of the low cost of tartaric ascorbic, isoascorbic, arabonic, sac- acid, the synthetic jiroccsscs are not charic, and glucuronic acids—cannot nov/ being used. However, the tartrates b(^ ]:>roduced at all, or only inefTiciently, in grape wastes are being successfully b\ the direct fermentation of dextrose. recovered on a large scale. It is esti- When not derived from natural mated that 10 million ]30unds of tar- sources, they arc generally made by taric acid is potc^ntially recoverable chemical conversion of dextrose. froin grajDC residues. Because of the threat of the synthetic processes, the LEVULINIG ACID has been manufac- price of tartaric acid may never again tured on a commercial scale by heating rise to the exorbitant levels reached in starch hydrolyzates with mineral acids. 1941 to 1946. The low cost, stability, and chemical activity of this interesting keto acid VARIOUS ASGORHIG AGTDS are known. have encouraged its development from They can be jirej^ared from corn sugar both a practical and a theoretical as the starting material. The most im- standpoint. Some of the compounds portant one, vitamin C, has the chem- that have been synth(\sized from ical name /-xyloascorbic acid. It is used ievulinic acid have been found to mainly in the treatment of scurvy and ])osscss local anesthetic and analgesic other diseases due to vitamin C de- action. Others have bactericidal and ficiency. It is thought that subnormal detergent properties. amounts of ascorbic acid in the body lead to ready infection with such dis- SINGE THE BEGINNING of the cen- eases as rheumatic fever, tuberculosis, tury, practical methods for the synthesis and diphtheria. of tartaric acid have been sought. The Of secondary importance is the com- search has been stimulated by the in- pound öf-ara!)oascorbic acid, which is creased use of the acid and its salts usually called isoascorbic acid. The as- and by our dependence upon foreign corbic acids have the same general sources of argols, the crude potassium formula, except that the hydroxyl bitartrate that crystallizes in wine bar- grou]) on the fifth carbon atom of cMch rels, from w^hich most commercial tar- has an opposite spatial position. Both taric acid is made. In the Second of these substances have similar anti- World War, the shortage of argols oxidant proj^erties, but isoascorbic acid brought the price of tartaric acid up has only one-twentieth the antiscor- from about 40 cents to more than 70 butic activity of vitamin G. Vitamin C cents a pound. To alleviate this situa- is found in nature in citrus fruits, cab- 782 1950-1951 YEARBOOK OF AGRICULTURE bagc. paprika, pine needles, and wal- The arabonic acid obtained from the nuts. It is generally produced com- calcium salt is rearranged to fi-ribonic mercially by the Reichstcin process (or acid by heating it in pyricline solution, a modification of it), whereby dextrose a process called epimerization. By de- is catalytically hydrogenated to d-sor- vious and costly methods, í¿-ribonic bitol, which may then be fermented to acid may be convertcxl to ii-ribose for /-sorbosc by a method developed by use in the ribofiavin synthesis. Proc- Department of Agriculture scientists. esses have recently been developed, The sorbosc is reacted wdth acetone in however, whereby ribose can be pre- the presence of sulfuric acid to form pared directly by the electrolytic r(^- diacetone sorbosc. Alkaline solutions duction of ribonolactone. The ribose is of the diacetone sorbosc are oxidized isolated as an aniline-ribosc-sodium with potassium permanganate or so- sulfate complex from which the ribose dium hypochlorite to diacetone 2-keto- can readily be obtained in crystalline /-gulonic acid, which, when hydro- form. It is believed that this develop- lyzed, yields 2-keto-/-gulonic acid. This ment will reduce the cost of making acid may be csterificd wdth methanol ribose to such an extent as to revive and then transformed to vitamin C by interest in the production of crystalline the action of sodium methylate. or it ribofiavin by chemical means. may be converted directly to vitamin G by heating with hydrochloric acid. By SACCHARIC ACID is more corrtx'tly an analogous procedure, the methyl named öf-glucosaccharic acid or d- ester of 2-keto-i:/-gluconic acid is rear- glucaric acid, because it is the dibasic ranged to produce isoascorbic acid. sugar acid derived from rZ-glucose by oxidation of the terminal groups. Al- Ti-iE criiEF VALUE of r/-arabonic acid though saccharic acid has been pre- lies in its use as an intermediate in the pared by the nitric acid oxidation of chemical synthesis of ribofiavin—vita- corn sugar and starch for more than a min Bo. The ribofiavin molecule con- century, no practical method for its tains a carbohydrate residue, which is large-scale production had been de- derived from íí-ribose. The 5-carbon vised until 1948. Chemists at the sugar, i/-ribose, is generally obtained Northern Laboratory have now devel- from the nucleic acids found in yeast oped a feasible process for making cells or from dextrose and arabinose, saccharic acid in yields nearly twice via arabonic acid. Arabonic acid is as great as those previously obtained. usually produced by the oxidation of In this process, corn sugar is gradually corn sugar in alkaline solution with added to concentrated nitric acid so as oxygen or air. In 1946, however, a new to maintain the temperature of the re- method of preparation was developed action at about 60^ C. After several at the Northern Regional Research hours the oxidation mixture is neu- Laboratory. In it, calcium 2-keto- tralized with potassium hydroxide and gluconate is electrolytically oxidized to then adjusted to the desired acidity calcium arabonate in 85 percent yield, with nitric acid to precipitate practi- in a manner similar to that used for cally pure potassium acid saccharate the production of gluconic acid. Ap- in 40 to 45 percent vield. parently in this reaction decarboxyla- The white crystalline product is fil- tion of the 2-ketogluconic acid first tered, w^ashed free of contaminating occurs. The resulting product is im- salts wâth w^atcr, and dried. It may be mediately oxidized to arabonic acid, converted to calcium saccharate by which is neutralized by the excess cal- reaction \vith a mixture of calcium cium carbonate present. Pure calcium chloride and lime. Saccharic acid may arabonate pcntahydratc crystals are be obtained by the addition of suffi- obtained by evaporation of the filtered cient sulfuric acid to remove the cal- oxidation liquor. cium ions as insoluble calcium sulfate. ACIDS OF MANY USES FROM CORN 783 Investigation of the practical applica- acids. They are also more palatable tions of the acid and its salts is now in when taken by mouth. With the excep- progress. tion of calcium Icvulinate, the calcium salts of the sugar acids are not soluble GLUGURONIG ACID is of great physio- enough in water for their efficient utili- logical importance. A detoxifying zation in the treatment of lactating agent in the animal body, it reacts with cows for hypocalcemia, or milk fever. such poisons as phenols anci amines to It is often necessar)' to inject as much form innocuous glucuronides, which as 50 to 75 grams of calcium gluconate arc eliminated in the urine. It is also a into the jugular vein of a cow in a significant constituent of fibrous tissue single dose. Such a treatment would and of heparin, the blood anticoagu- require as much as 1 to 2 quarts of a lant that is present in many of these saturated calcium gluconate solution. body tissues. The specific polysaccha- Various methods have been success- ride of type III pncumococcus, which ful in increasing the solubility of cal- possesses immunological reactivity, has cium gluconate. The introduction of also been shown to contain glucuronic boric acid results in the formation of acid in its structure. In 1947 an appar- soluble calcium borogluconate, which ent correlation bctw^cen glucuronic has been found to be an effective acid deficiency and rheumatic diseases source of calcium in veterinary medi- was discovered and the successful cine. Also in use are stable supersatu- treatment of a number of such cases rated solutions of calcium gluconate of with salts of glucuronic acid has been at least 10 percent concentration, made reported. The use of glucuronic acid by the addition of small amounts of as a dctoxicant in sulfa therapy has stabilizing substances, as calcium sac- also been indicated. charate, calcium salts of sulfonic acids, Although numerous attempts to pre- and strontium salts. The solubility of pare this important acid have been calcium sodium lactate in water has made in the past, no practical chemi- also been enhanced by the addition of cal syntheses were available until 1950, calcium gluconate. when the Northern Regional Research Since the discovery in 1906 that Laboratory and Corn Products Refin- antimony compounds are effective ing Co. independently announced therapeutic agents for the treatment of processes for its production. In the the protozoan diseases, African sleep- Northern Laboratory process, corn ing sickness and kala-azar, the death sugar is reacted with acetone and the rate from those diseases has declined product catalytically oxidized to ace- enormously. One of the original sub- tone glucuronic acid with air. Simple stances tried and one that still is in use hydrolysis of acetone glucuronic acid for the control of the diseases is the produces glucuronic acid which is iso- potassium antimonyl salt of tartaric lated in good yield as crystalline glu- acid. Another sugar acid antimonial, curonolactone. Translation of these sodium antimonyl gluconate, has been new processes to large-scale operation reported helpful in the treatment of will expedite both therapeutic and in- kala-azar. dustrial research on this sugar acid. Tartaric acid in combination with bismuth, as bismuth sodium tartrate or CALCIUM SALTS of gluconic, lactic, bismuth potassium tartrate, has been arabonic, and levulinic acids are being used intramuscularly to obtain the used in the treatment of calcium de- systemic eíTect of bismuth in the ficiencies in the human and animal treatment of syphilis. Bismuth potas- body. Because in water solution they sium saccharate has also been used. are practically neutral, they are less Water solutions of iron, copper, and irritating to the skin upon injection manganese salts of sugar acids are used than the calcium salts of the inorganic to obtain the effects of the respective 002722° -51 784 1950-19 o 1 YEARBOOK OF AGRICULTURE metal ions. Sodium lactatc has been been prepared for bactericidal pur- indicated for the prevention and treat- poses. The use of such compounds as ment of acidosis, and aqueous solutions ephedrinc gluconate, procaine glu- of magnesium eitrate have been used conate, gluconophenetid, and ergo- for many years as a saline laxative. tarninc tartratc has been indicated for More recently, citric acid and sodium the treatment of various ailments. citrate have become important for the preservation of whole blood. It appears C. L. MEHLTRETTER holds degrees also that sodium citrate may have in chemistry from the Polytechnic In- value in the treatment of lead poison- stitute of Brooklyn and Iowa State ing. Lactic acid has been used elTec- College. Since 1937 he has been en- tivcly as an aerial bactéricide. Ascorbic gaged in research on sugar acids and acid has been reported to be useful in related carbohydrates—3 years in in- the healing of wounds. Recently, cal- d.ustry and the rest at the Northern cium gluconate solutions have been Regional Research Laboratory. Dr. found of value in the treatment of bee Mehltretter's work is concerned with stings. Phenyl mercuric tartratc, glu- tJie development of industrial products conate, saccharate, and lactatc have from starch and dextrose.

VARNISHES were used in Egypt on mummy cases of the New Empire. Many are insoluble, but their method of preparation is not known with certainty. The earliest mention of the use of a drying oil in a process connected wdth painting is given by Aetius, about the sixth century. He stated that nut oils diy and form a protective varnish. From that time on, the use of dr\dng oils and varnishes seems to be well established and formulas for transparent varnishes composed of linseed oil and natural resins dating from the eighth or ninth century after Christ are known, Theophilus Presbyter, an obscure craftsman, who lived at the end of the eleventh century, used linseed oil wdth some kind of resin, probably amber, copal, or sandarac, to prepare oil colors. He worked out many formulas for paints, varnishes, and dyes. However, the discovery of the effect of driers in Hnsced-oil paints, w^hich is accredited to the brothers Van Eyck, was not made until the first half of the fifteenth century. The extensibility of oil on the surface of w^ater appears to have been known to Greek sailors, w'ho used oil to subdue waves during a storm. The phenomenon of surface tension of extension of oil on the surface of water was investigated by the great Hindu mathematician Bhaskara, who is presumed to have lived about A. D. 1114 to 1178,—K. S. Markley, Southern Regional Research Laboratory.