Jo~rn al of Research of the National Bureau of Standards Vol. 57, No.3, September 1956 Research Paper 2703 Purification of Substances by a Process of Freezing and

Fractional Melting Under Equilibrium Conditions I 2 Augustus R. Glasgow, Jr. , and Gaylon Ross

.\ purification technique has been developed whereby a mass of well -defined crystals, form ed by slow crystall ization of a liquid, .i s melted under eq uilibrium co nditions into a seri es of fractions. In this process the entire mass of t he substance is fractio nated into its gross impurities and high-purity material. This offers distinct advantages over co nven­ t ional fractional crystallization techniques. The apparatus provides for conducting the fractionating process in a closed inert system and is well adapted for purifying compounds t hat are corrosive, toxic, or reactive with air. Details of construction and operation of the apparatus, including experimental results on 2,5-dichlorostyrene, arc in cluded in t he report.

1. Introduction in solid solu tioll , (2) t hat crystals grow very slowly ill order to avoid occlusion of impurities, and (3) 11allY compounds of commercial and scientific that the crystals be large in order to minimize the importance may be toxic, rep ulsivc in odor, h~r gro­ volume of liquid r etained Oil their surfaces. scopic, corrosive, or reactivc with ail'. Further, In the crystalliza.tion of a single componen t from thermally unstable compounds, such as monomers its impure melt, it is a general practice to attempt or weakly bound compounds, are often susceptible the induction of crystal growth when the solution is to heat, and polymerize, dissociate, or isomeri ze at at a temperature slightly below the freez ing point. elevated temperatures. With many substances, ini tiation of the liquid-solid Purification of the above materials requires that transformation cannot be accomplished until the the fractionation process be conducted in a closed, liquid has cooled well below the freezing point. In inert system at low temperatures. These objec­ such cases, when crystallization occurs there is a. tives are largely attained by the combined sequence rapid growth of very small crystals, which results of equilibrium freezing and mclting: (1) crystals of in con tamination by occlusion in the crystal. In a single component (pme substance) are segregated particular, co mpounds with poor symmetr.v tend to from the other components (impurities) by cooling supercool. Aftcr t he onset of this in itial crystal­ the sample from its liquid state until crystallization lization, which star ts with the solution far from is substantially complete, and (2) the entire mass thermal equilibrium, the latent heat of fu sion of crystallized material is t hen slowly melted under rapidly rai.ses the temperature and closer approach equilibrium conditions to obtain. successive fractions to thermodynamic equilibrium is r ealized. On con­ (fractional melts) of increasingly higher degrees of tinued slow freezing of t he system, crystallization purity. This process is so analogous to fractional then proceeds in a more orderly fashion. In systems distillation that t he authors have suggested t he containing impurities conforming to the ideal con­ term "fractional m elting" to define the combined ditions enumerated in the first paragraph of this equilibrium freezing and melting process. section, the crystals preferentially select t he pure The technique of fractional crystallization has, of component and r eject the implll'ities. During this comse, long been used in pmification [1].3 Frac­ slow crystallization the crystals successively formed tional melting of a crystalline mass formed by slow from the solution are progressively less pure b ecause equilibrium freezing is more effective than crystalli­ of the difficulty of growing crystals of the pure zation alone in separating the entire mass of the component from solutions in which the impurities substance into its gross impuriti.es and high-purity are concentrated. Although each system of crystal­ material. A fractional-melting apparatus embrac­ lization has unique features, in general, very slow ing t he above principles has been developed and freezing produces crystals larger in size and with successfully used for the past several years. minimum occlusion. Optimum melting co nditions, using the apparatus 2. Fractional Melting of Ideal Systems described in this paper, are realized when the crystalline mass con tains large crystals of a single Ideal conditions for the separation of a crystal­ component and the impurities are segregated into a. line phase containing only a sin gle component separate liquid or a solid phase of smaller cryst als include (1) that t he impmities do not participate melting well below the freezing point. 4 of the single component. During the period of equilibrium melt­ I 'l'his research was supported by th e Diamond Ord nance F uze Laboratories of the Department of Defense. ing, the mass of small crystals containing the impuri­ , Presented at. the Gordon Research Con ferences of the AAAS on Separation ties is melted before the bulk of the large crystals. and Purification, Colby J unior College, New JJonci oll , N. R ., July 2, 1953; presented, also, at the 128th meeting of the Americ,n C hemical Society at M in­ neapOlis, Minn., September 11 to 16, 1955, bef) re the Division of P hYSical and 4 1'hcrmodynamically , "melting point" and "freezing poinV ' refer to the Inorganic Chemistry. • same equilibrium temperature and define the temperature at which an infinitesi­ 3 Figures in brackets indicate the literature I' rfC'l'cnces at the end of this paper. mal amount of crysta ls of the pure component is in equilibrium with liquid. 137 To summarize, the fractional-melting technique of t~e purification accomplished by progressive liquid solid-liquid fractionation uses equilibrium freezing to dIsplacement at the solid-liquid interface any obtain closer approach to ideal conditions for the recrystallization of the liquid to solid res~lt s i'n segregation of the impurities from a crystalline added purification. phase of the pure substance during the crystallization The apparatus used for the purification of a vola­ process. Equilibrium melting of this crystallized tile sample by fractional melting of the substance mass into fractions is then used to remove successively under its own vapor pressure is shown in ficrure l. impure material and finally the pure substance. A detailed drawing of the fractional-melting tube is shown in figure 2. Identical parts arc designated 3. Procedure and Apparatus by the same letters in both figures. The chamber of fractional-melting tube J, distributor Rand In the crystallization of a compound from its receiving ampoules W , are exhausted to ~ low impure melt, using the fractional-melting apparatus pressure (10- 5 mm Hg) by attaching the ground described in this paper, crystal growth starts at the glass joint C to a high vacuum system consisting of bottom of the container and proceeds slowly up a mercury diffusion pump and a forepump. The through the liquid. The crystals near the bottom evacuated system is then isolated from any stopcock lubricant by fusing the constriction at B in the glass of the tube are of high purity, with the bulk of the manifold. In this way the sample to be fractionated impurity concentrated near the top. After crystal­ lization the container is inverted and hcat is intro­ is exposed only to glass. The breakoff tip of am­ poule E is then broken by hammer D and the duced into the system so as to produce slow melting. The first material collected is the least pure and the sample is distilled into the cl1amber of the fr-actional­ melting tube. The manifold is then removed bv last portion most pure. In its downward flow, the sealing at A. . liquid 5 from the melted crystals bathes and washes Nonvolatile samples are transferred as liquids. each succeeding crystal surface. The less pure They are scaled under their own vapor pressure in material wetting the crystal surface is progressivel:"T displaced by liquid of higher purity. In addition to inverted breakoff tip ampoules [5], which are at­ ta,checl to an opening into the chamber below N in S If the v iscosity of the liquid c0n taining the impurities is high, sepa ration by gravity flow will be impra.cticable. Su ch systems will require addition of a soh -ent to lower th e viscosity. x

w y

F ______G

I';=====;-;==~ c B i- o

K .- E

M

L M I I I I I I I I I I I o 5 10 em

FIGURE 1. Assembly of fractional-melting tube, distributor and receivers, and manifold f or introducing volatile samples. FWU RE 2. Fracl1:onal-melting tube. 138 r ------, the figure. The evacuation and subsequen t removal I ------" " of the empty ampoule and the manifold are similar " " to that described for the volatile samples. " " The fractional-melting tube is placed ill a Dewar " " flask containing the freezing bath. ,A solid-liquid " " " slurry of a substance freezing at the desired tempera­ " " ture may be placed directl:v in the Dewar flask to LJ" obtain a constant-temperature bath. Ice and water are used for a temperature of 0° C, solid carbon diox­ H '\ ide refrigerant for - 78° C, and liquid nitrogen for RE FRIGER ATI NG - 196°C. OR HEAT IN G BAT H The temperature of the frrrzing bath required for nearly complete c1',\'stallization of tIle sample will depend upon the fl'eezing point, puri t." , and heat of fusion of tIl e compound being purified. For samples of high pu ri t.'- (98 mole percent or greater) and he~ts of fu sion hom abou t 2 to 4 k:cal/mole, a 1'reezmg bath abou t 5 to 20 deg (' lower than the freezing point of the sample is used. A cooling rate of the liquid neal' t he freezing point of the sample of 1 drg in 10 to 15 min is normalh-lIsed. This therm al head and cooling rate for such samples will all ow sub­ stantially complete cr.,'stalli zation in an overnight period of 16 Itr. Samples of lower purit.,- (80 to 98 mole percent), in which a largr temperature range is required for crntalli zation, wi ll req ui rc t he usc of several baths and 8 longe r time for t h r rr.,'staIJiza­ tion. FIG URE:3. Assembly lor melting operatioll . Transfrr of ene rg,'- across the space from the ou tel' wall, I , to or from thc . sample contained in the several degrces above t h e freezin g poi nl of the sample. chamber, J, is controll ed b.', the degree of eVaCllatl?n For lower-purit.', samples (80 to 98 mole percent), the of this space. In ordcr to p revcnt energ" T transfcr outer \vall is allowed to warm slowl.'- from at empera­ b.'- radiation, tlle inner glass s urfaces confining this ture nea l' the lowest crystalli zation temperature to a space arc sil ve rcd. The stopcock, X, in figure 2 1S temperature above the heezing point of the sample. connected to a high-vacuum s.,'stem through a vVi th samples of highcr purity t he melting opcration spherical joint, Y, and is used to adjust the pressure is llormally performed in a 6- to 7-h our period during fo!' a satisfactory rate of cooling or warming. the regular hours of the working da:,-. With samplcs The temperaturc of thc sample is measured witll a of lower purit:v, progressivc melti ng of t he sample thermocouple inserted in the closed tube, F , which requircs a longer time . . Becausc t he equipment was protrudes into the sample at K. An amorphous nonautomatic, the temperaturc of the bath during high-melting wax is used to flll the space between the melting process was varied during the da." , and a the thermocouple wire and the inner glass wall to a cOl lstant-temperatme bath waE uscd at night. depth of several inches abovc the thermocouplc Inorganic salts and ice have Been used to obtain j unction. When the sample has reached a tempera­ baths of high heat capacities fo1' retaining samples tlll'e slightly below its freezing point, crystallization overnight without appreciable melting. These baths is induced by cooling the small amount of the sample have been used for samples of low pm'it:,- that arc in the constricted portion, L, of the sample tube melted over a period longer than 1 cla.,-. Such appreciably below its freezing point. Coolant is mixtures are convenientl.', frozen by inserting a added through the glass tube, G, which is separated powdered carbon dioxide "cold finger " into the ap­ from part L of the sample tube b,\' theglass partition, propriate salt-water solut ion . ~1 . Samples freezing above - 50° C are cooled by Constant-temperatme baths described previously add ing powdered carbon dioxide, and samples for freezing the sample may also be used as melting freezing below - 50° C are cooled with liquid baths. The selection of the appropriate freezing and nitrogen [2]. m elting baths will depend upon the range of tem­ vVhen the crYstalli zation proccss is complcte, tile perature required for solidification and complete fractional-melting tube is inverted. It is then melting of the sample. When such baths are used, inserted in t he special Dewa'r-type vessel shown in the coils shown in figure 3 are removed from t he figure 3. The brass clamp, 0, supports t he fractional­ special Dewar-t.vpe vessel. If the melting opera~ion melt ing t ube and distributor. The small-diameter is performed during the working day, intermediate tube, N, allows some movement between these parts temperature baths between 0° C and solid carbon without breakage. For highCl-pmity samples (98 dioxide at - 78° C can be maintained manually by mole percent or higher), the outer wall of the frac­ periodically adding just enough solid carbon dioxide t.ional-melting tube is maintained at a temperature to a suitable solvent to keep the bath at a given 139 temperature. An alternate procedure is to circulate sample was cooled about 3 deg C below its freezing a liquid from a constant-temperature bath or refrig­ point. erating unit through coils placed in the Dewar, as In figure 4 the freezing and melting stages for this shown in figure 3. For substances freezing above sample are shown. In the first stage of freezing the room temperature the outer wall of the fraclional­ liquid was thermally shock-seeded at M with some melting tube may be heated electrically. powdered solid carbon dioxide. The first crystals Crystals are retained in the chamber of the frac­ formed quite rapidly and contained much occluded tional-melting tube by the conical perforated glass and entrapped material. This portion is shown as disk, H. The liquid from melted crystals is directed the hatched area in stage l. As crystallization con­ into the distributing funnel, R , by the dropping tip, tinued slowly up through the tube, the crystals that P. This funnel is ground at Q to a bearing surface, were formed, after the initial effects of su percooling upon which it is rotated. It was found in practice had been overcome, contained less occluded, or en­ that the friction of this bearing was sufficient to hold trapped, material. In the latter stages of freezing the funnel in a fixed position, and did not interferc the purity of the liquid had dropped to such a point with its rotation. A permanent magnet acting upon that the last crystals were formed in intimate contact the iron rod, encased in glass at S, is used to rotate witb the bulk of the impurity. In the case of the funnel to the various positions for transferring 2,5 -dichlorostYl'ene, at least some of the impurities melted fractions of the sample into the receiving were colored, so that when the entire mass (100 ml) ampoules, W . AU-bend, K, in a glass (4-mm was allowed to crystallize slowly overnight (16 hI') outside diameter) tube serves as a stopcock between it froze with the mass of impurities concentrated in the fractional-melting tube and the distributor. a highly colored cone at the top. This is sbown at This U is allowed to fill with liq uid, which is then Z in stage 4. frozen with a suitable cooling bat,h, while a filled It was also noted that as crystallization proceeded ampoule, also frozen , is sesled off and removed from in stages 2 and 3, the crystals became larger and the system at point V. In this manner the solid were embedded in a matrix of smaller crystals. plug in the U acts as a closed stopcock.6 After Crystallization with a constant-temperature bath, melting, liquid passes freely through the U. Foul' 0° C, became progressively slower throughout the additional ampoules (not shown) are sealed at freezing part of the experiment because of the de­ points T on the distributor and are filled in the Sim1l' crease in thermal head as freezing proceeded. Pro­ manner with subsequent fractiollsl n1l'lts. gressively slower freezing was very desirable in the present apparatus as no stirring was employed and 4. Substances Purified by Fractional the migration of the impurity away from the crystal­ lized mass was due to diffusion alone. Melting After crystallization the tube was inverted and, utilizing air at room temperature as a warming bath, This method has been applied to the purification the crystalline mass was slowly melted during a of 2,5-dichlorostyrene. A sample of this compound, period of 6 to 7 hr. The complete freezing and which had an original purity of 98.68 mole percent melting experiment thus required about 24 hr. and a freezing point of 8.058° C [3], was frozen in an Various degrees of melting are shown in stages 5, 6, ice bath at 0° C. The fractional-melting tube was 7, and 8. YIelting took place in accordance with then placed in a 4% liter Dewar packed with ice the purity pattern obtained in crystallization. water. This system, when insulated with glass wool, Fractions of 10 1111 each were collected. Nearly all held its temperature over the weekend to within 1 of the colored material was collected in the first deg C. The space between the walls (unsilvered in fraction. The first portion melted contained the these experiments to permit visible observation) was material in the core at Z and the mfl.t;:;rial near :\·1, pumped to a high vacuum to achieve a low heat which was first crystallized by shock-seeding. The transfer. Crystallization did not occur until the rate of melting of subsequent fractions became pro­ 6 We are indebted to R. 'I', Leslie of the Bureau [or t his technique. gressively smaller. In this melting operation, the

FREEZING MELTING

-1---2---3---4 - 5 --- 6---7---8~

H .... H Z

K K K

K K

H -'. H v H ../ ·• M ·

FIGURE 4. Fl'eez'ing and melting stages of 2,5-dichlorostyrene. 140 TABLE J . Summ.ary of fractional melting a se paration of 2,5-dichlorostyrene

Total impurity- Voium(' I mpurity for incremrnt perfecL Efficiency Fractional melting numbf' l' melted Pur it.\' lmp uriLY se paration b pel' stage Prese nt at Re moved in beg inning of the fracLio n Rcm ai nin ~ melting stage --.------:------.------1-----1------

a P urity on original sa mple 98.68 mole percent. b :Purity from summation of fractional 1T1l"' lts 98.64 mole percenL. c On basis ofincliddual frartionailTH'lts.

principal trall sfer of energy in to the freezing chamber 2.0 .------,------,------~------,------_, is through t he t hermoco uple well, K, the seeding well, G, and t he inner glass tube co ntaining the sample, rather than ac ross tlte space between the inner a ncl outer walls (see fi g. 2). ~ 1. 5 w F M -I T abl e 1 giv es a summary of the fractionation data. u a: w The purity values were determined from freez in g n. points obtained from melt in g curves [3]. This purity w pattern was obtained on blends of the fractions <5,.0 separated from 30 experiments on fractional melting, :;;; >­ using lOO-ml samples of tlte same stock materi al of I­ 2,5-dich.l orost)Tene [6]. Similar increments of vol­ ir :0 ume of the sample m elted from t he different ex peri ­ n. ~ .5 ments were bl ended . Three determinations of the F M -2 purit), were made b.\' usin g different experimental F M -3 groupings. These values of tlte purity cltecked those show n in the table. The se paration was therefore co nsidered rep resent ative of this compound 20 40 60 80 100 under these conditions. INCRE MENT MELTED, VOLUME PERCE NT

Figme 5 gives tilr total amoun t of impurity present FIG U UE 5. S epamt'ion of impurities jTom 2,5-dichlorostyrene at the various stages of mel ting (shaded bar) and as a function of volume percentage of sample melted.

the amount of impurit:,- rrllloved during the melting Shaded bar, total impurity in system at beg inning of m clting. Open stage (open bar). F~I- l , - 2, - 3, - 4, and - 5 refer bar, tot.al impurity removed in fractional melt. to the fractions coll ected when 20, 40, 60, 80, and 100 percent, respectively, of the substance had 100 .------,------,------,------,------, melted. In figure 6, the percen tages of impurity remo ved, , based upon the total amounts of impurity present at I- / Z 80 / the various stages of melting, are shown. The w u C r----,L'-- numbers 1, 2, 3, 4, and 5 refer to the fractions melted. a: I II w I / In the first fraction (C in the figure), 73.6 percent n. 1/..... 5 of the total impurity was removed. This initial 0 w 60 removal of impurity is attributed to the slow crystal­ > 0 lization 7 of the material and is not part of the im­ ::E w provement that occurs on fractional melting (M in a: >- the figure). The blocked lines represent the per­ I- centage of the total impurity (expressed in terms of ir 40 :0 the total impurity in the system before each succes­ n. 2 sive melt) removed in the fractioll. The circles are ~ .J

F I GURE 1 Schwab and Wichers point out in their work on benzoic acid l4J the impor­ 6. E.(ficiency of separation of impurities from tance of slow crystallization. 2,5-dichlorostyrene by jTactional melting. 141 purities if this fraction had been collected in smaller (1) The entire mass of the substance is fraction­ volume increments. This extrapolation was made ated into its gross impurities and high-purity ma­ on the basis of the progressive changes that took terial. place between fractions FY1- 2, FM- 3, and F~1-4 , (2) This method is adaptable to the purification as shown in table 1 under efficiency per stage. of small samples frequently encountered in research Two toxic compounds that decomposed rapidly problems. in air were also purified b.v~ this method.8 Each (3) Fractional melting is more efficient than compound had an original purity of about 99.7 mole fractional crystallization alone. percent. The last 50 percent to melt had a purity (4) Many compounds because of their toxicity of 99.95 mole percent. Titanium tetrachloride, and reactivity require that the solid-liquid fractiona­ which hydrolyzes rapidly in air and is reactive to­ tion be conducted in closed inert systems. The ward stopcock greasea, was successfull~~ processed fractional-melting apparatus described in this paper by using the assembly shown in figure 1. is well adapted to such compounds.

5. Summary a nd Conclusions 6. References [1) R . S. Tipson, Crystallization and recrystallization, A. Fractional melting consists in slow equilibrium Weissberger, Technique of Organic Chemistry, vol. III melting of a crystalline mass of a substance formed (Interscience Publishers, Inc., New York, N. Y., 1950). by slow equilibrium freezing. In general, for com­ [2] A. R . Glasgow, Jr., N. C. Krouskop, and F. D. RosEini, pounds that varied in purit~~ from 98.5 to 99.5 mole Anal. Chern. 22, 1921 (1950). [3] A. R. Glasgow, Jr., A. J. Strieff, and F . D . Rossini, percent, about 75 percent of the total impurity was J. Research KBS 35, 355 (1945) RP1676. separated in the fi.rst 20 percent of the melt. This [4] F. W. Schwab and E . Wichers, J. Research NBS 32, 253 technique of fractionally melting a mass of we11- (19-14) RP1588. defined crystals into a series of fractions of increas­ [5] A. R. Glasgow, Jr. , and M . Tenenbaum, Cryoscopic ingly higher purity offers the following distinct ad­ determination of purity of highly reactive substances. Anal. Chern . (to be published). vantages over conventional fractional crystalliza­ [6] G. S. Ross and A. R. Glasgow, Jr. (NBS, unpublished tion techniques: IYork) .

8 rrhis work was performed by ]\tfi lton Tenenbaum, who also assisted in the design of t he distributor shown in figure 1. 'V"ASHINGTON, 11arch 22,1956.

142