968
INDUSTRIAL AND ENGINEERING CHEMISTRY
gallons of oil per day. Indeed, the fortunate chance which directed this effort to fatty oils instead of petroleum oils has now worked out into a thriving, growing, and useful young industry. All of this has dealt with how molecular distillation came to be. Nothing has been said about what it is. Actually it is so simple as scarcely to need description. The material t o be distilled, the distilland, is caused t o flow evenly over a heated surface. Directly opposite this is a relatively cooler surface annular in shape. Between the two is as nearly nothing as it is possible to producea very high vacuum. The distance between the heated liquid film and the condensing surface is adjusted to be less than the mean free path of the molecules to be distilled. Across that gap, molecules jump. That is all there is to it except for an arrangement to catch the distillate. The key to the matter is in the production and maintenance of a sufficiently high vacuum, which must necessarily be greater with heavier molecules whose mean free paths are shortened by their greater weight. Research on this phase of the problem is complete to the point of commercial utility but not to the satisfaction of those responsible. They still think of interstellar space and real vacuity, even though present practice is less than a mere millionth of an atmosphere. Some of the aspects of this type of distillation are interesting. Utilizing molecular projectiles as is here done involves no boiling
VOL. 29, NO. 9
point as a control, no vapor pressure, no aeeotropic mixtures. Control of the process has been accomplished by adding to the distilland a dye, already found to volatilize simultaneously with the desired material, whose color indicates its presence in the distillate. The results of applying this technic t o fish liver oils have been to remove much of their odor and to separate from them vitamin A in the natural unsaponified condition in potencies up t o 500,000 units per gram., These ester concentrates can be saponified and redistilled t o produce pure vitamin A alcohol with a potency greater than 3,000,000 U. S. P. units per gram. The technic has also shown that there are several separate vitamins in the complex we know as natural vitamin D. Already on the market as products of this operation are cholesterol, vitamin A (esters and alcohol), and odorless vitaminless oil. To these, others soon will be added. The usual question we might ask in such a situation is: What further commercial development can be seen? The present attitude is to learn more about the process before deciding that. Experimental equipment will be made available for research institutions but will not at present be licensed for commercial application. The minutiae of this high-vacuum technic and of the results obtained with it are contained in the following papers by Hickman and his associates and in others soon t o be published.
APPARATUS AND METHODS K. C. D. HICKMAN Eastman Kodak Company, Rochester, N. Y.
M
OLECULAR distillation means the transfer of vapor
from the warmer surface of a liquid to the cooler surface of a nearby condenser, the space between the two being evacuated sufficiently to prevent any obstruction of the vapor. The free path of the majority of the molecules emerging is then less than the distance between the surfaces, and distillation occurs a t the lowest possible temperatures. The method was devised by Br6nsted and Hevesy (2) for separating the isotopes of mercury, and was adopted by Burch (S), Washburn (IS), and Waterman (14)for distilling other substances. To Burch we owe a complete new technology (4) for the purification of organic substances. The early molecular stills were of the simplest construction, consisting of two concentric vessels (2) or a vessel with a reentrant top (7). The bottom served as the boiler and the top as the condenser, and the space between the two was evacuated to about mm. The performance of such apparatus fell far short of the ideal. Under ideal conditions the separation of a mixed liquid by molecular distillation should be superior to that made a t higher pressures (3, 13) I n practice this is prevented ih various ways. The distilla is usually viscous and remains unstirred because the ebullition accompanying ordinary boiling is absent. The distilling surface becomes impoverished of its more volatile constituents and ceases to be representative of the bulk of liquid. The distillate fractions contain less of the light and more of the heavy constituents than they should. Also, the fractions alter during withdrawal from the still because part of the later condensate becomes mixed with part of the earlier as it flows slowly from the large condensing surface. These tendencies reduce the separation to less than the ideal. On the contrary, distillations a t higher pressures benefit from their imperfections because part of the distillate falls back into the boiler and is reevaporated. This secondary evaporation and the washing of the vapors which
it entails cause a better than theoretical separation and are, indeed, the bases of the a r t of fractionation. With the simple molecular stills many hours of vacuum treatment are needed to degas the material, and, although only the surface a t any moment is involved in distillatioa, the whole bulk of distilland is maintained a t or above the distilling temperature. Thus, the process which has been atlopted to save the material from thermal decomposition may actually involve a prolonged exposure to heat. These inherent drawbacks to the molecular pot still can be eliminated by making a still in two parts, one to store the liquid a t low temperature, the other to effect distillation . a t high temperature. By keeping L the mass of oil in the distilling region small compared with that in the storage space, the total exposure to heat can be diminished greatly. Furthermore, by bringing the substance a little at a time from one part of the storage space to the distilling region a n a returning it to another part of the storage sphce, some assurance can be gained that all portions of the substance have had a n equally favorable opportunity for degassing and distillation. This form of construction is, in effect, the one used commercially (4, FIGURE 1. SIMPLB 10) in continuous molecular stills FORMOF MOLECULAR where the substance is conveyed a little a t a time over a succesSTILL
c
SEPTEMBER, 1937
INDUSTRIAL AND ENGINEERING CHEMISTRY
sion of evaporators held at ascending temperatures. I n the present variation the distilland is recirculated over a single evaporator, the temperature being raised at each cycle. I n its simplest form, the substance is held by a receiver, A (Figure l), and is allowed to flow b y gravity over the distilling column to a second receiver, B. The column is now raised to a higher temperature, receivers A and B are interchanged, and the substance is allowed to flow over the evaporating surface again. The process is repeated as often as desired, a fraction of the distillate being collected during each passage of the distilland. It is not easy to substitute one rewnnn ceiver for another without admitting air or using complicated piping and (CONDENSER valves. Accordingly, a n evaporator was constructed in which the recirculaP tion of distilland is accomplished without interchanging reservoirs. The apparatusaims atcombining the advantages of a pot still with some of those of a multicolumn continuous still.
969
CONOENSATION
M1 FRACTIONATION PUMP ASSEMBLY CAPACITY 10-20 LITRES PER SEC.
Cyclic Still The essential parts of the circulating m o l e c u l a r still are shown in Figure 2 :
FIGURE 2. CIRCULATING MOLECULAR STILL
must travel in the distilland to reach the distilling surface is reduced fifty times, and, since the rate of diffusion is They comprise an an exponential function of thickness, the evaporator and conaccessibility of the surface to all moledenser, A , two resercules is largely increased. voirs, C and C', a cirThe internal manipulations of the culating pump, L, a still are controlled by a portable expreheating tube, F, ternal electromagnet (Figure 3a). Thus, and a w i t h d r a w a l the passage of the liquids is controlled mechanism, E. Beby steel balls1 (from ball bearings) it tween the evaporatwhich are allowed to block constrictions d ing column and the or else rest inactively in depressions in receivers is a cooling C the glassware. The passage of the oil coil, B. To use the from the upper to the lower reservoir is a p y a t u s , the liquid FIGURE 3. DETAILS OF STILL CONSTRUCTION controlled by the ball P (Figure 2), to edistilledis placed which can be removed from the conin the lower reservoir striction between the reservoirs to the and the vacuum is position C". The distillate passes through the filling chamber applied. The liquid is then pumped over the column and aland drop counter, D, and can pass back to the reservoir or to relowed to collect in the upper reservoir. The liquid usually ceiver E. This choice is determined by the position d or d' of froths, and quantities of gas are evolved. When one cycle has the steel ball. It has been found convenient to remove the distilbeen completed, the liquid is transferred to the lower reservoir late at atmospheric pressure rather than to use one of the welland a second cycle is performed while the column is warmed. known devices (16)which require that a predetermined number of (The liquid may be degassed unattended by allowing it to circureceivers shall be imprisoned in the apparatus until the end of late continuously with the ball displaced from the constriction the experiment. The removal of receivers is accomplished by between the reservoirs.) After a number of cycles, evolution of means of the ball valve between d' and E, and stopcock R. To gas ceases; and when the vacuum gage records a pressure of less make the change, the stopcock is closed and the receiver is pulled than 2 microns, the temperature is raised until condensation takes from its seating, but the distillate is prevented from returning by place on the walls of the receiver. The temperature is held conthe ball in F. A new receiver is laced in position, and when the stant until all the distilland has passed over the column. The fore vacuum has been reestablisted, the stopcock is opened and condensate is removed by changing the receiver, the temperature the liquid which has accumulated during the change-over passes of the column is increased, and the process is repeated until a sufinto the receiver. ficient number of fractions has been collected. With a careful disposition of parts, the quantity of material held at the distilling The magnetic circulating pump is made of nickel and glass and temperatures can be less than one-fiftieth of that maintained a t room temperature. Thermal decomposition is reduced fifty fold, 1 The halls have remained bright and uncorroded after months of use, and the quantities of gas to be removed by the vacuum pumps and there is no evidence that the distilland becomes contaminated with iron. are diminished in like degree. The average path that a molecule This holds true with oils rich in free fatty acids.
IYDUSTRIAL AND EVCINEEKING CHEaMISTRY
970
VOL 29,llio 9
hornlv refuses to spread, a column with a sum1 th; grokd top of the glass condensing jacket. The column finally adopted had the following characteristics: Effeotivs ieneth ?f di+iliina portion. om. Diameter indudin. 011 film em. ~pprox.dktiiling mea. 8 s Am. Tots1 area covered by oil atream. a s cm. AY. quantity oil ocau~yingworking a m race O f . A.; wantit? oil held, oc./sq. ern. I r . depth of oil, mm. AI. time of p ~ ~ e of g eoil over hot partion of column. Bee.
15 3.7 170
190 4
0.0235 0.236 201
The pressure of residual gas in the st.ill is measwed by a Pirani page, the setting of which is freouentlv checked aeainst a mmstar standard ZRBI?. The Pi& gage is artached to the still st i~ &&t farthest. from the pump manifold. For producing the v&cuum,any Condensation pump with B delivered canacitv of more tlian 15 liters ner seaond is suit.able. 'A sel"f-rt.ct,ifyingpump is recimmiided (8). A photograph of the r,omplett! assembly is reproduced in Figure 4.
Use and Performance of Still The still may be used for most purposes where a molecular pot 8 t i 11 i s i n d i c a t e d Natural waxes, mineral luhrioating oils, synthetic polymerized materials, plasticizers for molding plastics, and many other difficultly volatile substances may be purified or analyzed. Natural oils, such as c o t t o n s e e d or cod liver, may be distilled. From these, the essential oils and waxes are volatilized at temperatures below 100" C. The free fatty aeids are removed below 140" C. The free storols and vitamins are removed below 180" C., and the sterol and vitamin esters below 250" C. The glycerides begirl to distill a t 160' C., trilaurin coining over at about 180" C.; t r i o l e i n , linolein, and linolenin distill at the rate of n drop a second at temperatures r a n g i n g from 2%)' to 270' C. T h e comparative performance of the cyclic and the simple pot. still is shown iii F i g u r e 5, which records the concentration of iritamin A found in the fractions distilled from halibut liver oil. The destruction of the vitamin from prolonged hentingiil the potstill . !fFlouP.E 5. COMPARATIVB P E R is weil iiiarkcd. The . FoRMAttCE OF CYCLICAND SIMPLE POTSTILL full curves shox the apparent yieldof vitay in as dotermined by the3hlger vitameter. When, however, t.hedeterminationsak mede by the quartz spectrograph, much of the rnatcrial absorbing st 328 mp is not vitamin A hut is a prodiwt of pyrolysis. The pyrolyzed vitamin is present only in the fractions obtained a t the higher temperatures with the cyclic still. The pot still causessomedecomposition of all fraetions. The true vitamin A ciirvesnrerccordedashrokcnlines.
.
is owrrrted by an external electromagnet which reooives periodic imvulscs from a oendulum. The nluneer of the Dump is made
of
the'plun er A second ball rests on a co&icti;n in the pipe above; an8 the combination of magnet, hollow plun er, and two hall valves forms the complete pumf Details are 8kown in
cop
Figure 3b. The rate of circulation o f t c dlstliland is controlled by raising or lowering the intermittent magnet hy a screw adjustment, not shown. Perhaps the most critics1part of the assemhly is the distilling column. It should permit t,he distilland to flow in a thin, even si.ream over the surface. If the fluid rathers into rivulets or constituents of neighboring fractions tdoverlan in an unprodictother when the distilland is preheated to thv s i & temperature heating t i t o be used, the column may bk made of nla& or mkttl,
1 .
nickel-plated, tl& cliromium-&ted, and finally burnished to minirnirt. lirsses h y radiation. The distilland is spread on t,he oolumn bv alloninr it 1.0 fall into t,xo cnllers of wire piluze. the
SEPTEMBER, 1937
INDUSTRIAL AND ENGINEERING CHEMISTRY
Analytical Distillation The boiling point of a substance is the temperature a t which its vapor is equal to a specified pressure. This pressure is generally controlled by the gas (other than the vapor) also in the apparatus, so that the boiling point is observed as the temperature a t which the vapor overcomes the pressure of the residual gas. Below this temperature no distillation occurs; above it, distillation is vigorous. The point of transition is abrupt and obvious. Under molecular conditions there is by definition no foreign gas, and evaporation takes place whenever there is a difference of temperature between the distilland and the condenser. Increase in the absolute temperature and in the temperature difference increases the rate of distillation, but there is no abrupt transition available for observation and record. There is instead, as Burch pointed out, a relation involving both time and temperature. This relation is expressed for most substances by Langmuir’s equation; and the numerical value can be obtained if the dimensions of the apparatus can be measured accurately, if there is assurance of sufficiently high vacuum, and if the temperature of the actively distilling layer is known. These data are not always ascertainable; and, although excellent comparative results may be obtained by a n individual worker, when the results are compared with those of others, wide discrepancies may be found. I n any event, direct measurements of rates of distillation are applicable chiefly to pure compounds and afford little information concerning mixtures of dissolved substances. Fortunately it is possible to systematize the course of molecular distillation so that a property of the constituents of the distilland, analogous to a boiling point, can be measured. This can be done most easily for a type of distillation which has reached, temporarily, a position of some importance-namely, the elimination of small quantities of substances such as sterols, vitamins, hormones, or dyes, from a large bulk of less volatile fluid (oil). The procedure enables one to determine with some certainty the relative boiling points of two or. more constituents, to estimate qualitatively their heats of vaporization and, in the case of supposedly single substances, to pass judgment on their purity. The data can be obtained for substances in dilute solutions of unknown concentration and, thus, for materials which have never been obtained pure. For instance, one can determine the homogeneity of a vitamin, the general form of its vapor pressure curve, and its distillability in accurate relation to that of a known substance without necessarily isolating the vitamin or elucidating its constitution. The method depends on the following considerations.
97 1
material appears in the receiver. If the solution of potent material is exposed for distillation at constant temperature, the distillability remains constant with the lapse of time, but the rate of elimination, which is proportional to the product of the distillability and the concentration, decreases exponentially, approaching zero only after a long time when nearly all the potent material has been evolved. Such an elimination curve has the well-known die-away form. To hasten the elimination, it is usual in practice to raise the temperature of distillation step by step. The distillability now increases
FIGURE 6. ELIMINATION CURVES
progressively, but the rate of elimination, which a t first rises in like manner, soon falls to zero because all the potent material has evaporated. The curve has the general form shown in Figure 6. The exact shape of the elimination curve is determined by the procedure. Let the distilland be exposed for equal time intervals rtt each temperature, and let the temperature be raised so that the distillability is increased by an equal factor a t each step. As a n example, let the distillability be raised 1.26 times or doubled every third step, and let 1 per cent of the material be eliminated during the first interval. Simple arithmetic shows the trend of the elimination in Table I, from which curve a (Figure 6) results. The curve evaluated by calculus, is shown as b (Figure 6).
TABLEI. ELIMINATION DATA % of
Diatillabiljty or Intrinsic Rate of Distn.
-4pprox. Rate of Elimination
89.0 85.44 81.13 75.96 70.00 62.85 53.9 45.27 36.14 26.97
4.00 5.23 6.36 8.00 10.06 12.67
3.56 4.31 5.17 6.07 7.04 7.95 8.63 9.13 9.17 8.64
Time Material Interval Left in No. Distilland
Total % of Material Eliminated True Rate from of EliminsDistilland tion
The Elimination Curve The argument rests on simple postulates, the validity of which is left open to future examination. It is Qssumed that the trace of impurity (or “potent material”) has no affinity for the solvent and that it does not become preferentially located in or excluded from the distilling surface. It then follows that the quantity of potent material evaporated a t any moment will be proportional to its mole concentration in the main bulk of the distilland. Two kinds of rate of evaporation may be described. The first is the intrinsic rate of evaporation, or the distillability.*, It is defined as the ratio of the number of molecules of a given species leaving the distilling surface in any small interval compared with the number of similar molecules remaining undistilled in the surface layer during the same interval. The second is the rate of elimination or the rate a t which the * The word “volatility” is rejected beoause it has acquired more than one meaning; dee Walker. Lewis, and McAdams, “Principles of Chemical Engineering,” New York, iMcGraw-Hill Book Co.,1933.
6 7 8 9
PO 11 12 13 14 15
16.0
20.15 25.4 32.00
14.56 18.87 24.04 30.11 37.15 46.10 54.73 63.86 73.03 81.67
3.512 4.231 5,036 5.909 6.803 7.653 8,368 8.796 8.833 8,364
The curve is significant because its form is independent, within the assumptions made earlier, of the kind of substance distilled. It is the outcome of a conventionalized technic applied to the fundamental behavior during distillation of any kind of molecule. If an experimental curve has a shape
INDUSTRIAL AND ENGINEERING CHEMISTRY
972
a
VOL. 29, NO. 9 ~
~~
TABLE11. DISTILLATION OF VITAMIND Min. from Start 78 79 80 81 82 83 84 85 86 87 88 89
Pressure of Residual Gas 1.9p
96
97 98
1ZP 0
125,O
125,O 125.2 125.3 125.2 125.0 124,9 1.8p
...
1iLi:1 130.0 130.2
90
91 92 93 94 95
TemD. of Disiilland, C. 124.9
130:4
...
1.711
130.0 130.2 130 2
. .
Operationa
-HeaterMaintaining voltage
..
64.5
.. .. .. ..
..
A
..
.. .. .. b
Vitamin
Seo. a t full voltage
Av. Temp. during Run, C.
Mass of Fraotion, Grams
Averaged Mass Gram;
Color Intensity
Total Color
Potency; U. 8. P. X Units
Tptal Vitamin D
.. .. ..
120:0
3:i5
3:45
0:87
3:6
600
2665
. ,
,. ..
.. .. ..
.. ..
C
66.5
..
..
18
.. ..
.. .. ..
A
..
..
..
ii
C
'd
.. ..
.. .. 69 .'O
... ... ... ...
.. .. ..
B' D
...
.... .. ... ...
..
.. ..
126: 1
.. , .
.. .. ..
20
... ... ... ...
... ... ... I
.
.
.. .. .. .. ..
.. ..
..
.. .. .. .. .. ..
3.45
3:9
.. ..
.. .. ..
.. ..
..
..
.. .. ..
..
..
, .
..
.. , .
..
.. .. .. .. .. .. ..
.. .. 0:91
.. .. , .
.. .. ..
..
..
, .
..
.. .. ..
.. .. ..
.. ..
.. ,,
..
..
..
..
..
..
. t
.. ..
..
.. ..
, .
3:55
..
..
..
.. 780
..
,.
.. .. .. ..
.. ..
3100
..
.. ..
..
.. .. ..
, .
A = receiver changed; B = ball valve between reservoirs displaced; C = oiroulation of distilland stopped; D = circulation restarted. D 5 seconde, off.
differing from the normal, i t denotes a faulty distillation, or an abnormal substance which does not obey the simple postulates, or an admixture of subtances answering to one identifying test. The curve can thus reveal many of the properties of a substance and the kind of treatment i t has received. Besides a predictable shape, the curve has a maximum located on the temperature axis. The position of the maximum is dependent on the distillability and the length of the time intervals. If, for instance, the intervals are doubled in the example given, the whole curve is shifted to the left with little change of shape (curve c , Figure 6 ) ; the maximum occurs a t a lower temperature, again demonstrating that substances have no fixed boiling point in a high vacuum. An insufficient vacuum or poor renewal a t the depleted distilling surface introduces large variations in the shape and position of the curve. The former raises the temperature of distillation by an unpredictable amount; the latter spreads the elimination over a wider temperature range, flattening the curve and giving i t a reverse skew form, as shown in curve d. In extreme instances where the distilland is viscous and the renewal of the surface layer very poor, the temperature eventually rises so far that every molecule of potent material reaching the surface has enough energy to escape. Curve d commences a t low temperatures in the ordinary manner but soon assumes an extended die-away form which is modified slightly by the alteration in viscosity a t the highest temperatures. With standardized conditions, however, the curve depends only on the distillability; and the position of the maximum can be found with a precision of * l o C. The author suggests that this position is as valuable an attribute of a substance as the boiling point would be if i t could be determined a t a higher pressure. Distillability, in general, varies with the inverse of the absolute temperature, so that elimination curves of the shape shown in Figure 6 will be obtained if the temperatures are raised by constant fractions of the absolute temperature. Since, however, the increase of distillabilty for a given temperature interval varies from one substance to another, in the ratio of their latent heats of vaporization, substances with a high distillability increment will yield taller curves with narrower bases than those with low increments. Thus, the slope of the vapor pressure curve may be deduced from the inspection of the elimination curve. Any group of substances can be arranged with their distillabilities in serial order, provided the conditions of distillation are standardized. For these conditions the elimination
'
maxima occur in a fixed relative order with definite temperature intervals between each. Changing the conditions shifts all the maxima up or down the temperature scale but does not seriously alter the separation or the relative order except between substances of widely different latent heats. This enables one to use as distillation pilots (9) substances which are colored or are otherwise readily detected and estimated. The substances can be chosen t o cover not only the useful range of distillabilities met in molecular distillation, but also a wide range of latent heats of vaporization. When the approximate shape and position of the elimination curve of an unknown or experimental substance have been found, distillation can be performed again with the addition of an appropriate (dye) pilot, and the substance can be characterized as having an elimination maximum coincident with or separated by a definite interval from that of the pilot. Certain sterols and many of the substituted indigos and anthraquinone dyes are useful pilots. Thus, one may add methylindigo (pure indigo rubine) to the distilland in a molecular still and determine the temperature of maximum elimination, which may be, for instance, 140"C. Another worker, using an apparatus of smaller dimensions and operated with a higher distillation rate, may find a maximum for the dye of 165" C. The f h t operator would find a maximum of approximately 115" C. for vitamin A; the second, approximately 140" C. The differing maxima have the common characteristic that they occur 25 " below that of methylindigo. Further distillation would reveal that the maximum of the vitamin is nearly coincident with that of Celanthrene Red 3B, thus characterizing the material beyond ambiguity to both workers. The practical application of the method involves many compromises. It is inconvenient, if not impossible, to pdistill traces of substances from nonvolatile distillands. The distillate collects as a mist on the condenser, and the apparatus must be dismantled to remove each fraction; or a stream of oil must be kept flowing uniformly over the condensing surface to dissolve and carry away the distillate. It is more convenient to allow the distilland to evaporate simultaneously with the potent material. Indeed, i t is the nature of most oils to do so. It is not their nature to evaporate a t a uniform rate throughout distillation; consequently, some fractions are large, others small. The drainage from the large condensing surface is slow and the completeness varies with the size of the fraction. The material collecting in the receiver appropriate to one fraction may be chiefly material distilled during the previous interval; and the overlap and intermix-
.
SEPTEMBER, 1937
INDUSTRIAL AND ENGINEERING CHEMISTRY
ture of the fractions are unpredictable. The bulk of the distilland and, hence, the concentration of the undistilled potent material vary rapidly with the withdrawal of a large fraction, slowly with a small, introducing abnormalities in the elimination curve which require laborious correction.
Constant-Yield Oil Distillations done to identify (rather than separate) a constituent require adjustment of the distilland so that the rate of evaporation and the drainage error are kept uniform throughout. The (potent) material under examination should be dispersed in a medium which yields a similar volume of distillate for each succeeding temperature interval, without, however, reducing the volume of distilland by more than half a t the end of distillation. Allowing 2 to 3 per cent for each fraction, collected a t 5 O to 10O C. intervals, the elimination curve does not differ greatly from those shown in Figure 6. Embree (6) has calculated the ~ h a p ebut , ~ it is necessary also to find it by experiment in order to include the drainage errors of the apparatus. The dispersing medium, or constant-yield oil (C. Y. 0.1, could be made b y blending various nonreactive solvents, such as heavy petroleum fractions. For the examination of sterols, vitamins, and hormones, a mixture of synthetic glycerides has been found preferable because it is readily absorbed by animals during biological assay. The mixture also proves suitable for oil-soluble dyes. It has been prepared by heating glycerol with a number of higher fatty acids and an excess of butyric acid. Glycerides of various types are produced, such as mono-, di-, and triolein, -stearin, -caproin, etc., glycerol monobutyrate dioleate, etc., and glycerol dibutyrate monooleate, etc. The mass is freed from its lighter constituents by partial distillation a t 1.0 mm. in a wide-necked flask (I%!),and the residue is evaporated in the molecular still, Part of the large fractions is rejected, and the remainders are blended, redistilled, and reblended until distillation yields fractions of similar bulk. A full account of the preparation of the oil is being presented elsewhere (1). The finished constant-yield oil is generally used in one of two ways-as an addition to an oil, the constituents of which are under examination, or as a blend with pure distilled cottonseed or cod liver oil from which the accessory substances have been removed. This blend is suitable for determining the purity and position of the elimination maximum of dyes or substances already in concentrated forms. Experience has been gained with analytical distillations made a t 10-minute time intervals and with temperature increases varying with the inverse of the absolute temperature passing from 100' to 105' C. as the first step; also with uniform temperature increases of 10" and 5' C., respectively, over the range 90' to 260" C. The elimination curves are obtained by the following procedure which was adopted as standard towards the conclusion of this work. The determination of the elimination curve of vitamin D from saponified cod liver oil will be described to illustrate the procedure.
Preliminary Test of Still Forty cubic centimeters of constant-yield oil were mixed with 60 cc. of pure diluent oil (a high-boiling fraction of cod 3 When the conditions for securing reproducible elimination curves were first being studied, the author used to maintain a constant rate of distillation or appearance of liquid in the receiver, raising the temperature each cycle
sufficiently t o ensure uniformity. This gave elimination curves of the shape deduced earlier only because the distilland happened to be a nearly perfect constant-yield oil. When other distillands were used, the elimination curves were harely recognizable. Embree painted out that the temperature should be raised by constant increments, irrespective of the properties of the distilland. This generalization put the work on a quantitative basis.
973
liver oil, free from accessory substances) and 1mg. of dipropyldiaminoanthraquinone was added as pilot. The mixture was distilled in the cyclic still, using 10" C. temperature and 5-minute time intervals. The distillation was repeated on similar mixtures using 10- and 20-minute time intervals. The elimination curves of the blue dye were compared for the three distillations, and, although the latter two were similar in shape, the first one had the reverse skew form which denotes poor renewal of the distilling surface (circulation was too fast). 10
B 8 8
0 e-
--
1
B
B 0
x
6
k-
2 6IJ
Q Q
8
U 9-
z
s
0 0
a
4-
4 3 -
X EXPERIMENT N O 164 88 88 0 'I I66 'I
0
6 T E M P E R A T U R E OC
FIGURE 7.
DIETHYLDIAMINOANTHRAQGINONE
ELIMINATION CURVES
Oil-heated column, 50' C. preheat
Distillation was repeated twice with 5 " C. temperature intervals, adopting the 10-minute interval as the shortest time practicable. The dye curves in Figure 7 demonstrated that the maxima were repeatable and that the shape was almost that demanded by theory. Vapor pressure data (11) had already shown that this dye has a heat of vaporization almost identical with cholesterol, so that the dye elimination curve should be of similar shape and should, as a first approximation, be suitable for matching vitamin D.
Final Distillation The nonsaponifiable material from 500 grams of medicinal grade, Norwegian cod liver oil was added to a mixture of 80 CC. of C. Y. 0. and 120 cc. of pure diluent oil. After allowing the solution to circulate overnight in a vacuum of 10-a mm. a t 50" C. to remove gas, collection of distillate was commenced a t 90" C. The magnetic pump was adjusted so that the upper reservoir of the still emptied in exactly 9 minutes. After 9 minutes the ball intercepting the two reservoirs was withdrawn, and circulation was continued for 1 minute more to allow displacement of the oil in the pipes and pump. -4t the conclusion of the tenth minute, circulation was stopped, the current supplying the column was increased to 110 volts (full current) for a number of seconds and then adjusted t o the value required to maintain the column a t the next temperature, 95" C. The times for the application of full voltage and the voltage to maintain the steady temperature were found from charts compiled previously. At the commencement of the twelfth minute, the circulation of oil was started, the ball separating the reservoirs was returned, and, after 1 minute the thermometer was inspected. (It should indicate exactly 9 5 O C.) At the thirteenth minute the receiver was exchanged, and the hands of the clock were shifted back to the 2-minute mark. The cycle was repeated, the teniperature being raised 5" C . each time. Twenty-three fractions were removed, the highest a t 200" C. The fractions were weighed and the weights plotted against temperature. From the smoothed curve the most probable weights of the fractions were ascertained. The concentration of dye in each fraction was compared with that in one fraction arbitrarily used as standard, a red filter being placed over the eyepiece of
INDUSTRIAL AND ENGINEERING CHEMISTRY
914
the color comparator to minimize variations in tint of the diluent oil. Vitamin D was estimated biologically, using onerat assays (6). The data and an appreciation of the precision attainable can be gathered from Table I1 and Figure 8. The vitamin has a tall, narrow elimination curve, suggesting a vapor pressure curve steeper than the parent cholesterol. 10
z9 Pa 5-l
56
9" 8 4 : 3
2 2 0 D I E T H Y L D l A M I N O ANTHRAQU
I 120
130
140 190 160 TEMPERhTURE OC.
170
1FP
FIGURE 8. CODLIVEROIL-VITAMIND CURVE
This is a characteristic also of calciferol. The maxima of both substances occur a t nearly the same temperature as diethyldiaminoanthraquinone. The shape of the vitamin D curve is abnormal, suggesting the presence of three antirachitic substances, present in the ratio '/a to 1 to l/4 with maxima at 120", 150",and 175" C., approximately. A fuller investigation is in progress. ,
Scope and Precision of Distillation with Pilots
VOL. 29, NO. 9
possible with the antirachitic bodies can be gathered from the same figure if the temperature differences are taken as approximately four-fifths of those marked on the left-hand side. In either case, a second substance can be detected if present in half the quantity and boiling 10' or 15" C. from the main constituent. When smaller quantities of nearer boiling point are present, the only effect is to shift the position of the maximum to a false location. The remedy is to fractionate the parent material and secure curves for the head and tail portions. Pilot dyes are, perhaps, most useful in studying the action of new apparatus or in assisting the first isolation of an unknown substance. For the latter purpose it is convenient to use two dyes of widely different distillability, such as Celanthrene Red 3B (123" C.) and Quinazarin Green (190" C.) in the hope of bracketing the substance. After distillation into as many fractions as practicable, the maximum of the substance is located by test or assay. From the color of the fraction, a single pilot can be chosen and thereafter multiple fractionation can be conducted, the concentration of the substance being followed ; by the increase in color, checked only g occasionally by test or biological assay. Considerabletimeand 0 many test animals ?20 130 140 160 100 I70 are saved, and final TEMPLRATURL ' C assay levels can be FIGURE9. D I E T H Y L D I A M I N O Predicted m x ~ o m i ANTHRAQUINONE FAULTY DISTILLATIONS cally from the color of the sample. There Resistance-heated column, 800 c. preheat has as Yet been no evidence of interaction or destruction Of the experimental material by the dye. A number of Pilots With approximate mmima are given in Table 111.
Much more work must be done before the contention is substantiated that dyes afford precise means of comparing distdlabilities. The apparatus and the procedure were altered progressively during the evolution of the method, so that early curves for both dyes and vitamins do not coincide with later ones. The curves in Figure 7 agree well because all the procedures were identical. In contrast, the curves of Figure Acknowledgment 9 show the variations that were met when using the same It will have been appreciated that the distillation procedure sample of pure diethyldiaminoanthraquinone in differently outlined here is of the simplest and oldest variety known to compounded oil mixtures, distilled with varying degrees of man-namely, that of placing a mixture in a still, heating preheat, etc. the mixture, withdrawing successive portions of distillate, Often curves of entirely abnormal shape are encountered, and examining the portions for change of composition. -No The question arises as to how thoroughly a mixture of substances obeying the same test (e. g., two or BELOW AOOVL more dyes of similar color or a mixture of antiI:I rachitic substances) can he resolved. The a -f3 3 -k 4answer is that they cannot be resolved easily with analytical distillation. It is necessary 9 t o apply repeated fractionations by ordinary molecular distillation and then to compare the elimination curves of the extreme fractions by analytical distillation from constantyield oil. (The homogeneity of natural vitamin D is now being tested in this manner.) 'The probable resolution of a binary mixture has been studied by constructing composite curves representing the addition to one substance of quantities varying from one fourth to equal quantities of a second substance loo answering the same test. This second substanceis supposed todistillat 5", lo", 15", 20°, 30", or 40" C. above or below the chief constituent. The composite curves for thevariations are shown in Figure 10 for typical compounds, such as the anthraquinone dyes, cholesFIGURE10. COMPOSITE CURVESFOR VARIATIONSIN TYPICAL COMPOUNDS terol, and vitamin A. The greater resolution
~NDUSTRIALAND ENGINEERING CHEMISTRY
SEPTEMBER, 1937 TABLE
MaIM.4 111. APPROXIMATE
Name
OF PILOTS Relative Eliminatio; Max , C.Q
Formula
127
Dimethyldiaminoanthraquinone
97s
Burch, C. R., and Bancroft, F. E . , Brit. Patents 303,078 and 303,079 (Sept. 21, 1927); U. S.Patent 1,955,321 (April 17, 1934).
Embree, N. D., IND.ENQ. CHEM.,29, 975 (1937). Hickman, K. C. D., Ibid., 29, to be published (1937). Hickman, K. C. D., S. FranklinInst., 213, 119 (1932). Ibad., 221, 215 (1936). Hickman, K. C. D., Nature, 138, 881 (1936). Hickman, K. C. D., U. S. Patent 1,925,559 (Sept. 5, 1933). Hickman, K. C. D., Hecker, J. C., and Embree, N. D., IND. EKQ.CHEM.,Anal. Ed., 9, 264 (1937). Hickman, K. C. D., and Weyerts, W. J., J. Am. Chem. SOC.,52, 4714 (1930).
Washburn, E. W., Bur. Standards S. Research, 2,476 (1929). Waterman, H. I.. and Elsbach. E. B., Chem. Weekblad, 26. 469 141
Diethyldiaminoanthraquinone
(1929).
Young, Sydney, “Distillation Principles and Processes,” p. 18, London, Maomillan Co.. 1922. RECEIVEDJune 1, 1937.
153
Communication 029 from the Kodak Researoh
Laboratories.
158
CO
Dipro yldiaminoa n t Braquinone
NCHi
NHC~HI 162
THEORY OF ELIMINATION CURVE N. D. EMBREE Eastman Kodak C o m p a n y , Rochester, N. Y.
KHChHs I71
Dibutyldiaminoanthraquinone
183
N H C H i a C H s
/v
NHCsHii
Dixylyldiaminoanthraquinone 210-2 15
217
Quinizarin Green
Hickman (2) has shown that certain substances which distill under molecular conditions may be studied and identified by means of elimination curves. Such curves are derived here by theoretical methods. The effect of the properties of the substances distilled and the effect of the nature of the distillation procedure upon the shape and location of these curves are indicated by several examples.
NH? Anthraquinone Blue
Sky
183
/v “2
a Determined approximately with 10’ C. temperature intervals; more accurate d a t a with 5’ intervals are being compiled.
multiple purification, generally called “fractionation,” has been attempted, since the author’s purpose has been to extend a little the degree of precision attainable with simple evaporation under molecular conditions. In this he has been aided by collaborators, each well versed in some part of the work. It is a pleasure to acknowledge indebtedness to J. C. Hecker for suggesting the double reservoir for the cyclic still; to J. G. Baxter and A. 0. Tischer for preparing large quantities of constant-yield oil; to J. G. Baxter for making the pure pilot dyes; to E. LeB. Gray for performing the more accurate distillations; and to N. D. Embree for making many suggestions concerning the theory of the work.
Literature Cited (1) Baxter, J. G., Tischer, A. O., and Gray, E. LeB.,“Preparation and Characteristics of Synthetic Constant-Yield Mixtures,”
to be published. (2) Brgnsted, J. N., and Hevesy, G., Phil. Mag., 43, 31 (1922). (3) Burch, C. R.. Proc. Roy. Soc., 123A,271 (1929).
T
H E degree of separation which can be obtained by molecular distillation is not much better than that given by distillation in a simple pot still at higher pressures. The concentration of a substance in the material condensing is proportional to the partial pressure in the distilland in pot distillation; in molecular distillation it is roughly proportional to the partial pressure divided by the square root of the molecular weight of the substance. This property of molecular distillation .makes it impossible to separate, by a single distillation, substances having values of the P to ratio which do not differ considerably. I n those cases where information concerning the constituents of a mixture is required rather than their separation, Hickman ( 2 ) has shown that much may be learned from a single, carefully controlled molecular distillation. The mixture is exposed for evaporation for a certain time a t each of a series of temperatures, and the amount present of a substance being considered is measured in each fraction. These yields, plotted against the temperatures at which the fractions had been distilled, provide a distillation curve which Hickman (6)has called the elimination curve. The amounts of the substance in each fraction increase with the temperature a t first, since the vapor pressure is increasing. The yields, however, findly reach a maximum and then decrease rapidly to zero because the supply of the substance in the distilland becomes exhausted. The elimination curve has an easily recognized
da
