September 1951
I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
suc:c~css~ul course in applied statistics can only be given by one n-ho has specialized in the field of application. Certainly the average student of chemistry would have difficulty in obtaining much of practical value from the usual course in mathematical statistics. College and university schedules are undoubtedly already overloadtd, but i t would be well for t,he various faculties t o compare the value of some of the material now given with t h a t of a course in applied statistics and so determine the advisability of niakiiig room for the statistics. I t can certainly be concluded t h a t graduates with statistical training will kw of more value in certxin fields than those without it. Introduction of morc courses on applied statistics for chemists, however, would be only a temporary Polution. The change that, is to be desired is more far-reaching than this. Universities do not offer a dozen or more courses i n applied mathemat,ics or applied English. Why should it he nccessarv to have so ni:iny courses in applied statistics? Eventually, it should be powible t o teach statistics in a nxiiiner similar to t h a t in which mathematics is now taught. The student. takes t,wo or more courses in niathematics given by a Inathematician. H e learns his npplicd mathematics incidentally t o his coui'ses in physics and phg-ric:il chemistry. U71ij.cannot statistics be haridled in t,he same way? A basic course i n mathematical statistics given by a statistici:tn should lay the foundations for future applications. This type of training has been discussed by Snedecor ( 1 ) and by JVilks ( 2 ) . I t equivalent t o the general training in mathematics given should a s a pr,eiequisite t o all advanced scientific study. But such trttinirig would fail in its purpose unless it3 principles were eshauetively applied. The applicationi; should permelite all subesample, the, sequent courses of a quantitative nature-for course in quantitative :iiialysis should make use of control charts in studying experirniintal erroi', Experiments in phywical chemistry should be used to illustrate the design of exprr~inients arid statistical analysis of results as well as the l n \ w u i d phcnomena of physical chemistry. Couiws i n industrial clieniistq.
should include study of control charts and some of i 1 : i t tLi methods of trouble shooting. Statistical methods ofi'er a bag of tricks that is almost aliva>.s useful and is sometimes :in absolute necessity. But there is inon> to it: Modern statistics is a formalization of much t h a t is instinctive t o a first-class experimenter. The explicit expression 01' these principles of sountl esperimentation is helpful t o exprrinienters of all grades arid can be counted on t o decrease their mistakes and to increase their efficiency. The far-reaching importance of the subject justifies its iriclusiori in the edurat,ion of :ill experimentalists. It is too much to hope that a revolutionary change in chemical curricula can be r:ipidly effected. For the present it will be ii major advance for representative chemistry department* t o install courses in applied statistics. However, there is liopc' that the time will come when statistics and statistical methodology are as much a pmt of our common way of thinking ns are the algebra, el&ir:nt:ir!. c:ilrulus, :md granimnr lenrncd :it R I I early age. It appears that industrial chemists m e now more awaw of thy importance of statisticaal training for chemists tliari are tht, university chemists n h o give the training. I n order to infoi,m the faculties of the extent t'o which training of this type is needed, each of us who has found it useful must appeal to app1,opriatc members of his Alma RIater t o 1,ecognize the w e d and to do something about it. If such an appeal is made i n sufficient volume, favorable action n41 rwult, in the not. too distant futiiri.
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ACKNOWLEDGMENT
The author is indobtecl to Irene hlontz and &Lie 1'. Hildt.lirandt for tabulating the c o u r s t ~in statistics listed i i i t l i t a various catalogs. L r r m u m r m CITED
(1) Snedecor, George IT., J . A m . S t o t . Assoc., 43,53 (1948). ( 2 ) Wilks, S.S., Ibid., 46,1 (1951). KKCEIVED ;ipril 21. 1951. I.nitad States Rubi,er C'o.
C(,riti.ihution So. 114 fi,oiii ( h i i t ~ r i i l1 . ~ 1 ~)
: t r 0 1 n 1 ~
(END OF SYMPOSIUM)
Organic Derivatives f Alginic Acid ,iRNOLD H. STEINER AND WILLIAM H . 3IcNEELk' Kelco Co., Sari Diego, Calif.
Previous attempts to prepare organic derivatives of alginic acid adaptable to commercialization have met with little success. Drastic conditions required to accomplish substitution by the usual reagents largely destroy the colloidal properties of the polymer. As a part of a research program designed to extend the range of usefulness of algin, alginic acid has been found to react under mild conditions with various alkylene and substituted alkylene oxides to give a unique series of algin products. These water-soluble alkylene glycol alginates give viscous solutions at relatively low concentrations. In contrast to sodium alginate, these esters are soluble in acid solutions. The algin derivative, propylene glycol alginate, is now available commercially. 1 ts pronounced thickening and
emulsifying powers in acidic solutions have resulted in extensive commercial application in such uses as French dressing, salad dressing, flavor emulsions, meringues, pharmaceutical jellies, and foam stabilization. e
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N 1881 while attempting to find a use for the seaweeds which
were abundant around the 13ritish Isles, Stanford (20, 21') discovered a colloid that he named algin. H e then spent thc next few years establishing the properties of this water-solublt. gum which he obtained by an alkalitie digestion of several species of brown algae. The alkali salts such as sodium and potassium alginate as \vel1 as ammonium alginate were found to give viscous aqueous solutions at remarkably l o a algin co~iceiitrations. These watc.i,-solul)li, algins were precipitatd from
2074
INDUSTRIAL A N D ENGINEERING CHEMISTRY
solution a8 fibers or gels by the addition of bivalent and trivalent metal ions such as those of calcium and aluminum or by strong sei&. It wss not until 1929 that modem industrial methods and extensive research were employed successfully to establish an algin industry in the United Ststes. This growing industry is largely based on the giant kelp of the Pacific coast. Figure 1 shows 8 view of the giant kelp or Macrocijslis pyrzfefera.
Vol 43, No. 9
REACTTON OF OXIDES WITH ALGINIC ACID
Alginic acid reacts relatively rapidly under mild conditions with alkylene oxides to give weter-xoluhle estera (8#-S6). Of paramount interest here is the reaction of alginic acid with the commercially available propylene oxide. .4lginic acid, when well dried, is B horny miid that msy be difficult to redissolve even in s l h l i n o solutions. It is probable that hydrogen bonding hetvoon sdjaoent chains and also betwucen segments of the same moleeulc-not unlike the hydrogen honding in ~ o m cprotein molecules-is largely responsible for the lack of reactivity of alginic acid in the dry state. Ilowever, wheri alginic acid is dried only partially so that it is in a fibrous and swollm condition, it is in .e condition to react with oxides. P R O P Y L EOXIDE. N~ The ability of propylene oxide to react with alginic acid is, no doubt, due partially to iL3 miscibility with nalcr. Added oxide disaolves in the watcr md then is al>k fa penetrate the water swollen fibers. The esterification of the carboxylic seid group of alginic acid takes place slowly a t room tt’mpcmture but considerably faster a t a slightly elevated ttmperatuw with an upper limit of approximately 75’ C. Owing to the high VRpor pressure of propyleno oxide in this temperature range the reaction is carried out in equipment suitahle for oprration under moderate prmire. Thc properties of propylene oxide might suggest that tho principal reaction under theso conditions would be hydrolysis of thc propylene oxidr to propylene glycol. IIonover, the reaction rate of alginic acid with propylcne oxido is much higher than was expected. Thus, it is possihlc to esterify a substmtial fraction of the carboxylic acid groups of alginic acid without excessive loss of oxido by hydroly-sis. Figure 3 shows the relationship bctwcen ?!in moks of oxide per equivslent of alginic acid and tlic resultant mole per cent esteiifieation of thc nlainic . acid. The shaw of thc curve indicates that SO to 7570 esterification is readily obtained, hut essentially oomplete rsterifieaiion is ctthor difficult to 8ccomplish. The reac,t,ionproduct of propylene oxide and alginic acid, pro-
The properties of algin me best appiecintcd by cmminieg thc strucburr of alginic acid given in Figure 2 , Y = TI. .Alginic %eidis s polymer of anhydro-8-o-mannuroriic acid of colloidal dimensions (10, 15). There is one earRouy group for each anhydromannuronio acid residue. It is this free carbon) group that is responsible for thc formation of insoluble precipitates or gels on thk addition of certain mota1 salts and strong acids to aquoous solutions of soluble alginates. In addition i to the earboxy group, algin has two hydroxy groups I for each anhydro-mannuronie acid residue that are potentid pltlces for attaching organio substituents. o=c-or Y O*C-OY Considerable effort has been expended in the past to attach substituents to these hydroxy or carbory groups as shorn by more than a dozen pittents and publications ( 1 4 , 8-11, 14, 15,# 7 , 6 8 ) . Most of this previous work was carried out with the object of obhining derivativcs that could be uscd to obtain structural information on algin, and little of cornrnercial value has resulted from these investigations. Reports in the literature showed that tho carboxy groups could be prtrtially methylated only with considerable difficulty andunder conditions that effectively AX destroyed the colloidal properties and commercial Figure 2. Alkylene Glyool Derivatives of Alginic Aoid value of the product. The hydroxy groups have been acetylated only under difficult and commercially expensive conditions. Recently, B sulfuric acid ester of algin receivod favorable reports a8 a blood anticoagulant in medicine (18,19). A- high molecular weight docs not appear to be necessary for this appylenc glycol alginate, probably mainly consists of 2-hydroxyplication. In general, in the previous invostigations mild conpropyl alginate although lesser quantities of isomer, I-hydroxyditions and reagent7 have left the alginic acid relatively unmcthylethyl alginate may he present. The structure of this touched, whcreas conditions drastic enough to result io substitualgin derivative in shown in Figure 4. The isomeric ester group, tion havc usually rosultcd in extensive reduction in the molecular if present, would bo distributed randomly along the algin chain. size and colloidal properties of the algin. As part of a research program designned to extend the range of ETBYLENE OXIDB. Ethylene oxide resots with alginio acid under conditions similar to those found for propylene oxide; usefulness of algin and to prepare tailor-made algins for specific the equipment must bo modified slightly to accnmmodste the applications, organic derivatives of alginic acid were investigated.
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INDUSTRIAL AND ENGINEERING CHEMISTRY
September 1951
gaseous ethylene oxide. The product, ethylene glycol alginate, can esist only in one form, 2-hydroxyethyl alginate. Sriom C I i A I N OXIDES. Additional lower oxides, butylene oxide, isobutylene oxide, pentylene oxide (1,2-epoxypentane), and triniethylene oxide were prepared by heating the corresponding chlorohydrin or acetosy chloroalkane Yith potassium hydroxide according to the usual methods ( 1 2 , I S ) . The chloroh>-drinswere prepared by treating the olefins v\ith hypochlorous
,
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EQUIVALENT RATIO OF PROPYLENE OXIDE TO A L G I N I C
ACID
Figure 3. Effect of Variations in Propylene Oxide to ifginic Acid Ratio on the Per Cent Esterification 15 mole yc of carboyyl groups prr-rnt as sodium salt
2075
after 24 hours oiily a minor fraction of the carboxylic acid groups is esterified. This contrasts sharply with the results when 10 to 20 mole 7"of the carboxylic acid groups is neutralized with a base to give the carboxylat,e ion prior to reaction; the reaction is strongly exothermic, the pH rises rapidly as acid groups are esterified, and a practicable esterification is obtained within a few hours. PROPERTIES O F N E W A L G I N A T E ESTERS
There is no general agreement regarding the relative contribution of various factors to emulsion stability, but gums corit,ribute to the s t a b i h y of emulsions by increasing the viscosity of the aqueous phase and also, in some instances, by contributing protective colloidal action. The term "emulsifier" is commoiil>, reserved for those substances that have hydrophilic and lipophilic port,ions in the same molecule. The emulsifier molecules then can form an oriented film a t the interface with the lipophilic portion of each molecule in the oil phase and its hydrophilic portion in the water phase. The alkyl-ne glycol alginates combine in the same molecule the action of a true emulsifier with the thickening and protective colloidal properties of the gums. Figure 5 gives a curve showing the infiuence of the chain length of the glycol on emulsion stability. This is an arbitrary, quickbreaking test at 50" C.; the x a t e r viscosity is adjusted to 100 :p. in each test by the addition of sodium alginate if necessary. The emulsion stability increases rapidly with chain length reaching a maximum with an 8- or 10-carbon side chain. The alkylene glycol alginates can be prepared with little apparent degradation in molecular size as inferred from their viscosity in water. Propylcne glycol alginate, known in the trade a s Iielcoloid, is the only alkylene glycol alginate that is commercially available. This new algin derivative is a povider, readily soluble in hot or cold water. I t gives t,he high viscosities a t low concentration that, are characteristic of the algins. Figure 6 shows t,hat Kelcoloid HV gives a viscosity of 1000 cp. a t a concentration of less than 1.5%. Kelcosol, a liigh viscosity sodium alginate, reaches a viscosity of 1000 cp. a t less than 1% concentration, and Kelgin LV, a low viscosity algin, requires a concentration of a p proximately 2.5% to reach 1000 cp. viscosity. Thus, the viscosity of propylene glycol alginate is comparable to that of sodium alginate.
xc,id or .V-chlorourea ( 6 , 13). The reactivities of the lower normal 1,2-epoxyalkanes, ethylene oxide, propylene oxide, butylene oside, and pentylene oxide with alginic acid were ali similar, giving n-ater-soluble esters v i t h ti0 t o 80 mole yc esterification. \k hen isobutylene oxide x-as reacted, the oxide hydrolyzed so mpidly with water that only 33 mole 7c esterification of the :tlginic acid could be obtained when 3 moles of oxide per equival m t , of alginic acid was employed. A surprising feature {vas the reactivity of the 1,3-epoxide-trimethylene oxide. This fourmembered oxide ring appeared to open as readilj- as the threeuienibered 1,2-epoxide ring on reaction with alginic acid to give 3-hydroxypropyl alginate. The structures H H H u i these alkylene glycol alginates are given in Figure 2. 1,on.G CHAIS OXIDES. The higher glycol alginates H-I-{-i-H were prepared in order to compare the length of the side OH H chain alkyl groups n-ith the ability of the corresponding alginate to stabilize emulsions. The tedious preparation ot the oxides from the olefins via the chlorohydrins, employed by Findley, Swern, and Scanlan ( 7 )to epoxidize H/i-o\r I unsaturated fatty acids, was avoided by direct peracetic arid oxidation of the olefins to the oxides. By this nieans the 1,2-epoxides of hexane, heptane, octane, decane, and dodecane were prepared with yields varyC ing from 30 to 60% of the theory. In addition, t'he H H 9,lO-epoxides of stearyl alcohol and stearic acid were prepared by the same method. llainly because of decreasing solubility in water, H H the mole per cent esterification of the alginic acid H H H J X devreased rapidly with increasing chain length of the Figure 4. Propylene Glycol Alginate oxide. In fact, the mole pcr cent esterification apuroached zero ranidlv with higher members of the As a result of the blocking of a large fraction of the carboxyl series. By adding glycerol to increase the solubility of the higher groups with a propylene glycol ester, this alginate ester is soluble oxides and partially neutralizing the alginic acid with a base prior in acid solutions that will precipitate sodium alginate as alginic t o reaction, a minimum esterification of 20 mole % could be obacid. At pH's above the neutral point propylene glycol alginate tained even with the higher members of the series. is gradually hydrolyzed to propylene glycol and alginate ion. REACTION MECHAKISM.The main reaction course takes place Thus, propylene glycol alginate extends the usefulness of the through the alginate ion rather than alginic acid. Although algins to acidic solutions. In addition to acid resistance, propylalginic acid will react with the oxides, the reaction is slow; even
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INDUSTRIAL AND ENGINEERING CHEMISTRY
2076
ene glycol alginate has a n improved rcsistance to precipitation by calcium and other metal salts. Propylene glycol alginate is not a n allergen (16), and extended animal feeding tests a t 50 to 100 times the level t h a t it would ever be expected to appear in thc diet have demonstrated t h a t it is harmless. APPLICATIONS OF PROPYLENE GLYCOL ALGINATE
Under the trade name of Invilmulnent for inoid grov t i 1 u ('nvisited und the riiolcls fouiid ~ V V I Y , for the most p:trt,, mcnilwi~s0 1 t,he gcnera Aspergillus o r P e n i c i U i u m . Siiiiilur t r s t s by 1':i I t,arisky and hIcPhi,rson ( 7 ) o f t h t b iiiolds groniiig on p : h t l i l i i l b sholvcd these gener;l to I)(:tht. iiiost rommon typc's r e p i ~ w n t c ~ l . .4s these molds arr krlowii to t w \yicic>sprc:id and prolxibly til(, most reprcscrltntivc of t h c ( ~ o n i n i o l 1fungi, one spwic.s of c:ii5li t>.l)(' )vas selected for t,hv tcxsts w i t h t l w concrett': :L g r c ~ i i~ I ~ Y X ~0 1 ( Y Penicillium mold and rispcrgi'ilits niger. The nioltls \V(II'(' vkilt u i d o n potato dcstrosv : ~ g : t rI!? 1 1 1 :~ ~ c c ~ p t mc~tliod. c~l
