ANALYTICAL CHEMISTRY, VOL. 50, NO. D. H. Fine, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., 1977, in press. S. T. Fan, I. S. Krull, R. D. Ross, M. H. Wolf, and D. H. Fine, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., 1977, in press. I.S. Krull, T. Y. Fan, M. Wolf, R. Ross, and D. H. Fine, in "LC Symposium I.Biological and Biomedical Applications of Liquid Chromatography", G. Hawk, Ed., Marcel Dekker, New York, N.Y., 1977, in press. D. H. Fine and D. P. Rounbehler, J . Chromatogr., 109, 271 (1975). D. H. Fine, D. P. Rounbehler, A. P. Silvergleid. and R. Ross, in "Proceedings of the 2nd International Symposium on Nitrite in Meat Products", B. J. Tinbergen and B. Krol, Ed., PUDOC, Wageningen. Zeist, 1976, p 191. M. J. Downes. M. W. Edwards, T. S. Elsey, and C. L. Walters, Analysf (London), 101, 742 (1976). W. Fiddler, R. C. Doerr. and E. G. Piotrowski, paper presented at Fifth IARC Meetina on Analvsis and Formation of N-Nitroso COmDOUndS. Durham, N.H, August i977, in press. B. C. Challis, A. Edwards, R. R. Hunma, S. A. Kryptopoulos, and J. R . Outram, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., 1977, in press. H. Ohshima and T. Kawabata, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., 1977, in press. R N. Loeppky and R. Christiansen, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., August 1977, in press. S. S. Singer, W. Lijinsky and G. M. Singer, paper presented at the Fifth IARC Meetina on Analvsis and Formation of N-Nitroso ComDOunds. Durham, N.H, August i977, in press. T. Y. Fan, R. Vita, and D. H. Fine, Toxicol. Lett., in press. M. Mandel, D. Ichinotsubo, and H. Mower, Nature (London), 267, 248 (1977). R. M. Angeles, L. K. Keefer, P. P. Roller, and S. J. Uhm, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., August 1977, in press. 0. J. Logsdon, 11, K . E. Nottingham, and T. 01 Meiggs, paper presented at the 91st Meeting of the Association of Official Analytical Chemists, Washington, D.C., October 1977, Abstract 215, in press. R. Ross, J. Morrison, D. P. Rounbehler, S. Fan, and D. H. Fine, J . Agric. Food Chem., 2 5 , 1416, 1977. T. Y. Fan, J. Morrison, D. P. Rounbehler, R. Ross, D. H. Fine, W. Miles, and N. P. Sen, Science, 196, 70 (1977). D. H. Fine, D. P. Rounbehler, E. Sawicki, and K. Krost, Environ. Sci. Techno/., 11, 577 (1977).
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(2 1) Eisenbrand and Spiegelhalder reported nitrosation of solutions containing aminopyrine when washed through a Kieselguhr column which contained traces of residual nitrite, personal communication, 1977. (22) G. Eisenbrand,B. Spiegelhalder,C. Janzowski, J. Kann, and R. Preussmann, paper presented at the Fifth IARC Meeting on Analysis and Formation of N-Nitroso Compounds, Durham, N.H., August 1977, in press. (23) W. Fiddler, J. W. Pensabene,R. C. Doerr, and C. J. h o l e y , FoW' Cosmet. Toxicol., in press. (24) S. S. Hecht, R. M. Ornaf, and D. Hoffmann, J . Natl. Cancer Inst., 54, 1237 (1974). (25) T. Y. Fan, U. Goff, L. Song, D. H. Fine, G. P. Arsenault, and K . Biemann, Food Cosmet. Toxicol., 15, 423 (1977). (26) S. S. Mirvish. Toxicoi. Appl. Pharmacoi., 31, 325, (1975). (27) D. J. Freed and A. M. Mujsce, Anal. Chem., 49, 1544 (1977) (28) G. R. Umbreit, CHEMTECH., 7 , 101 (1977). (29) D. H. Fine, F. Rufeh, D. Lieb, and D. P. Rounbehler, Anal. Chem., 47, 1188 (1975). (30) R. Stephany and P. L. Schuller, in "Proc. 2nd International Symposium on Nitrite in Meat Products", B. J. Tinbergen and B. Krol. Ed., PUDOC, Wageningen, Zeist, 1976, p 249. (31) I.S. Krull, U. Goff, M. Wolf, and D. H. Fine, FoodCosmet. Toxicology, in press. (32) T. A. Gouah, K. S. Webb, M. R. Pringuer. and B. J. Wood, J . A@. Food Chem., 25, 663 (1977). (33) D. H. Fine, R. Ross, D. P. Rounbehler, A. Sitvergleid, and L. Song J . Agric. f o o d Chem., 24, 1069 (1976). (34) B. C. Challis, personal communication.
RECEIVEDfor review December 16, 1977. Accepted January 27, 1978. W e thank t h e U S . National Science Foundation (NSFGrant No. E N V 75-20802), t h e U.S. National Cancer Institute (NCI Contract No. NOI-CP-45623), t h e U.S.Environmental Protection Agency (EPA Contract No. 68-02-2363 and 68-02-2312), and t h e U.S. National Institute for Occupational Safety and Health (NIOSH Contract No. 210-77-001) for financial support. Any opinions. findings, conclusions, or recommendations expressed in this paper are those of t h e authors, and do not necessarily reflect the views of the KSF, NCI, EPA, a n d / o r NIOSH.
Spec if ic Pentaf I uo robenzy lat ion of Phenols in a Biphasic System J. M. Rosenfeld" D e p a r t m e n t of Pathology, McMaster University, Hamilton, Ontario, Canada L 8 S 4J9
J.
L. Crocco
Drug Analysis Laboratory, McMaster University, Hamilton, Ontario L 8 S 4J9
Conditions are described under which phenols are pentafluorobenrylated in a biphasic methylene chloride/sodium hydroxide system, but in the absence of phase transfer catalysts such as crown ethers or quaternary ammonium hydroxides. The reaction conditions are shown to result in specific pentafluorobenzylation of phenols. The reaction rate increased with the concentration of pentafluorobenzylbromide in the organic phase and sodium hydroxide in the aqueous phase. For the three phenols studied, an increase in molecular weight resulted in an increase of reaction rate.
Pentafluorobenzylation has been used to develop highly sensitive methods for t h e quantitative determination of organic compounds in biological matrices (1-6). Recently, Davis has described some novel conditions for t h e pentafluorobenzylation of carboxylic acids and phenols, described the gas chromatographic properties of t h e derivatives, and discussed 0003-27C0/78~0350-0701$013010
t h e mechanisms involved in t h e preparation of' t h e pentafluorobenzyl derivatives of these compounds ( 7 ) . Most methods for quantitative determination of a n organic compound in a biological matrix t h a t use pentafluorobenzylation involve extractive alkylation in a biphasic system (1-4). Extractive alkylation and phase transfer catalysis have been extensively reported as useful methods in preparative organic chemistry (8-20) and the mechanism of action of phase transfer catalysis has also been studied (11-14). Since extractive alkylation is applicable t o a wide variety of functional groups and alkylating agents, it has also proved useful in the development of methods for the quantitative determination of organic compounds in physiological substances (15- 21). However, the general reactivity described in these reports also implies a lack of selectivity in the extractive alkylation reaction. We now describe a biphasic reaction t h a t results in alkylation of phenols but in the absence of phase transfer agents. When phase transfer agents are not used, t h e reaction is F 1978 American Chemical Scciety
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* ANALYTICAL CHEMISTRY, VOL. 50, NO. 6 , M A Y 1978
specific for phenols, sirice carboxylic acids are ncjt alhjlatetl. I n addition, phenols of different molecular weights react at, different rates, t h u s enhancing t h e specificity.
EXPERIMEN'I'AI, The phenols studied were obtained from the follorving ~trurccs: ig-Tetrahydrocanna~inol~ courtesy of H . A. Graham. Chief, Scientific Services. Food and Drug Directorate, Department of National Health and Welfare, Ottawa, Ontario; Estradiol from Steraloids; a-Naphthol from Eastern Cheinical ('orporiit ion, Pequannock, N.J. Radiolabeled estradial tritiated at 6.7 a i d with a specific activity uf 40- 60 PCi was purchased from New England Nuclear, Bustvn. hlass Thin-layer chromatography iti:med I hr radiulabel to be chromat ographicall~equivale::t estrarlir~lanti radiocherni~allypure. Pentafluori~b~iiz)-I h r u n i i ~ viing anioiii~tsu t estradiol U d J cdrried i ~ u i varying the arnount of PFkB added from 0 to L O O pl. arid rhe tising a variation uf the a h m e method. Samples cuntaining 5OUOO concentration of sodium hydroxide from 0 tu 1 0 N.Afier haking dpni, c~~rrespunditig I ~ 100 J I J ~trf'estradiol, were diluted wit 1 1; for 1 h, the aqueous phase was diluted with 0.a hI phosphate hiffer I O . 100, IIMIO, Mid JOOlX) ng of cold estradiol carrier. EaLh of iliese a t pH 7.4. The acjueuus phase uaa aspirated, {he organic pliant ~9til1ilebuaa sulieded t o the hiyhuaic clerivatimtion desc,rilrd wah diluted with inore nit~thrlenecliloride, anti dried v.itli bldilJrii dlioce. l'he experimerits were r u n i n two sets of triplicates. J i i sulfate. External standard was added to the d r y organic. phase: oiie sei I I i~x i p l i c d v s , the raclimctivity in the dried wethvleiie the solution waq decanted into 3 second tdJe and taken tb tirynes3 I hl*?Iidelayer wa; deieriiiintd dti,tctl>,, h i the seco~idset U T under nitrogen ulth warming in a m i d bath at 70 'i. The i-&d.de triplicdteh, the dioacii\,iLk w h L O c h ~ ~ m a l u y r ~ p hOII t cthiii t layer was taken up (Jn 50 GI. cf heptane and a 1- i o alkl.iot bf this raditil and pciitafl~icirolie~iz~l es r!trrcimal (-]graph,. uith culd cohinli, In the solution was injected on1 (J a gas chroina~o~ra~iliic tradiol ib1iic.h served as carriers for tlir ~.hrornatci~raphic idencase of estradiol. the residue has first taken tip in 100 P I . tificatioii. The spots were visu'ilized by iodine staining arid BYTFA/TMCS (911) kept a i 25 "(' for 10 min, evaporated to scraped into roLlnting Lials a i d iadiolabel determined in Bray's dryness, and the residue treated as previously desc~ribed.'I'lie ('tchtail. T h e remaining poItiun6 of the plate were cut into 1-cm following external standards were used. In the stud? I J f tlhr reactions of AY-l'HC;the external standard R ~ AS 9 . ' I ' l . I ~ ' - ( ~ ~1 ~ e t h ~portion5 and the radioactivity was determined. etherj *Inthesized h! mt.t;hcids p;e; i3tdsl) d R Ed t,' I ,'I 5 A h L) 1)1 S( ' I I SS 1 C, N S study of the reactions cf esrradiol, the txternal standard was methyl tetracosanoate. ?'he external stalidard fur ilre s t d y of P'eiitdluut obeiizylatioii i ti t lit. abseiice of ~oiinterioiiswas the reaction oi u-riaphthol was methyl pentadecamate. The stud) &er\ ed for the lhree cases studied arid a t all concentrations of the hydrolysis of pentafluorobenzg'l stearaie iiiid pentaof base. In all iiijtaices. higher concentrations of base resulted fluorohenzyl tetracosanoate was carried out usiilg niet h) 1 tetill a higher degree of conversion i n t h e 1 - 1 1 time period. In racosanoate as an external standard. addition for t h e three compounds studied, those with higher The gas chromatographic conditions and retellticin times were ~noleciilarweight required lower concentrations of hase f(Jr ion of the 13--THC was as follows. The analysis (if the r quantitati\.e con\,ersion. ' h u h , l9-TI1C was quantitatively performed on a 1.52-m. 4-mm i.d. g columu pacsked with 3% converted t o t h e ~ ~ e i i t a f l u o r o t i e t i zderivative ~l when the SE-30 on a Chromsorh W 80/100 mesh and maintained at a concentration of NaOII was 5 N or higher. T h e results for temperature of 270 "C. 'l'he retention times were: 4 inin for estradiol arid n-naphthol are summarized in Figure 1. Below .19-THC;3.08 niin for A9.T€IC l-(l-methyl ether; and 6.85niin for pentafluorohenzyl AY-THC.The analysis of tlie reaction of 5 h' NaOH, pentaflriorotienzvlation was always observed b u t the est,radiol was performed on a 1.52-ni, 4-mm i d . column packed the degree of conversion was variable. Quantitative conversion with 3% OV-17 on Chromsorb W 80/100mesh and it maintained was defined as t h e recoveries obtained from t h e extractive a t a temperature of 315 " C . The retention times were: 2.10 inin alkylation (that is, biphasic: derivatization carried out with for estradiol his(3,17-trinieth~~lsilyl~ ether, 1.68 min for ethyl 'THAII). This recovery was taken as quantitative for t h e tetracosanoid, and 5.07 min for estradiol 17-trimethylsilyl 3following reasons. Derivatization by extractive alkylation has C)-peritafluorobenzyl ether. 'The analysis of the rt'actiun of c t Itcen shown t o he quantitative ftor a variety of substrates and naphthol was performed on a 1.83-111,4-mm i.d. glass column a1k:~~Iating agents ( I , % , 3 ,19, 23). When quantitative recovery, packed with 1.5% 01'-17 on Cliroinsorb W 80jL00 mesh and a s determined by t h e above definition, did not occur, it was maintained at a temperature of 185 "C. The retention times were: 3.21 min for a-naphthol; 5.27 min for methyl tetracosanoate. and possible under the described experimental conditions to detect
ANALYTICAL CHEMISTRY, VOL. 50, NO. 6, M A Y 1978
703
mle=12¶
mle
Figure 2. Mass spectrum of 17$-trimethylsilyl estradiol 3-0-pentafluorobenzyl ether
t h e parent phenol. T h e phenol was not detected in t h e extractive alkylation case, nor in those cases t h a t were carried out in t h e absence of T H A H , but which showed a recovery equivalent t o extractive alkylation. Last, as outlined below. studies with radiolabeled estradiol showed quantitative conversion t o t h e pentafluorobenzyl derivative. T h e mass spectra of all derivates prepared under the biphasic reaction conditions showed ions a t m / e = 181, thus confirming t h a t a pentafluorobenzyl group has been incorporated. In addition, the mass spectrum of the silylated derivative of pentafluorobenzyl estradiol showed a n ion at m/e = 524, which corresponds t o t h e molecular ion of monosilylated pentafluorobenzyl estradiol (Figure 2). This indicates that the reaction product is the 3-0-pentafluorobenzyl ether. T h e dependence of the degree of conversion on concentration of alkylating agents and substrate was studied using estradiol. This phenol was chosen because estradiol is soluble in alkali (24) and its methylation by extractive alkylation has been described and shown t o be quantitative (23). Over the range 1 ng t o 10 gg, all of the radiolabel was recovered in the methylene chloride phase. Thin-layer chromatography showed t h a t in all cases. the radioactivit) co-chromatographed with estradiol-3-0-pentafluorobenzyl ether. No significant radioactivity was found a t any other position on the plate. These d a t a show t h a t over a concentration range of five orders of magnitude, the pentafluorobenzyl derivative is reproduciblk and quantitatively formed. I t therefore appears t h a t in 1-h reaction time, t h e degree of conversion is independent of substrate concentration. T h e degree of conversion, however. was found t o be dependent on concentration of pentafluorobenzyl bromide (Figure 3). T h e lack of dependence of t h e degree of conversion to substrate concentrations indicates t h a t these reaction conditions and t h e mechanism involved are applicable t o problems in analytical organic chemistry. In order t o test t h e generality of pentafluorobenzylation in t h e absence of counterion, carboxylic acids were also studied. Since the lipophilicity and solubility of the substrate in methylene chloride might be important considerations in determining reaction rates and specificity, stearic acid and tetracosanoic acid were subjected to the reaction conditions that resulted in the pentafluorobenzylation of phenols. Stearic acid was chosen because it has one carbon atom less but the same number of oxygen atoms as estradiol. I t should. therefore, be slightly more water soluble than the steroid and is a n appropriate model of carboxylic acid t h a t is relatively soluble in base. Tetracosanoic acid has three carbons more t h a n 1 9 - T H C and is therefore a good model of a highly lipophilic acid. In addition, Gyllenhaal has demonstrated the preparation of pentafluorobenzyl stearate from stearic acid by extractive alkylation (1). Under the described conditions. no pentafluorobenzyl ester of either acid was found. However.
801
a 1 0'
,
,
10
20
mMOLES x
1
1
1
30
40
50
,
,
60
70
PENTAFLUOROBENZYL BROMIDE
Figure 3. Per cent completion of reaction of estradiol as a function of the amount of pentafluorobenzyl bromide in the reaction mixture. Each point is an average of three determinations with the relative standard deviation described
pentafluorobenzylation of these two acids could be achieved if counterion was added t o t h e reaction mixtures. Furthermore, pentafluorobenzyl esters could be quantitatively recovered from t h e reaction mixtures after shaking for 1 h in methylene chloride with 10 N base. Therefore, failure t o detect pentafluorobenzyl esters of stearic and tetracosanoate acids cannot be attributed to t h e formation of t h e ester and subsequent hydrolysis by strong base. This evidence suggests that pentafluorobenzylation of carboxylic acids does not occur under the described conditions. The specificity of the reaction conditions for the derivatization of phenols is apparently not attributable t o t h e differences in the degree of ionization. Under the described conditions which use high concentrations of alkali, there is no difference in t h e degree of ionization between t h e phenol and t h e carboxylic acid. I t is t o be expected t h a t both phenol and carboxyl groups are present in the aqueous phase as the phenolate and carboxylate anions, respectively. Two other alkylating agents, ethyl iodide and ethyl bromide, were also studied. There was no evidence of reaction taking place in the absence of phase transfer catalysts. Evidently, the reactivity of the pentafluorobenzyl bromide with phenols in the absence of counterion is attributable t o t h e chemical reactivities of the alkylating agent and substrate. I t is possible that the phenolate anion and the pent,afluorobenzyl bromide are a matching set of soft Lewis acid and bases. Ethyl bromide and ethyl iodide may be insufficiently soft for reactions under uncatalyzed conditions. Dockx ( 8 ) and Jones (9) in their reviews of phase transfer catalysis and extractive alkylation, have discussed the importance of the theory of hard and soft acids and bases t o t h e understanding of t h e mechanisms involved in these reactions. T h e fact that pentafluorobenzylation occurs in the absence of phase transfer catalysis i s unexpected. However, it does
704
ANALYTICAL CHEMISTRY, VOL 50, NO. 6, M A Y 1978
suggest t h a t both t h e anion and the alkylating agent are present in the same phase. It is therefore likely t h a t the phenolate anion and the ethyl bromide or ethyl iodide, under our conditions, must also be present in the same phase as the anion, but in these instances, the reaction does not occur. This indicates that the counterion may be more than a simple phase transfer agent (13) and may play a more complex role in the mechanism of action in phase transfer catalysis or extractive alkylation. T h e lack of reactivity of the carboxylate anion can have several explanations. I t is possible that the carboxylate anions d o not enter the same phase as the pentafluorobenzyl bromide or they may enter t h e same phase but may be solvated to a different extent t h a n t h e phenolate anions. When phenols are determined in physiological matrix via nonspecific derivatization methods, it is necessary to separate these analytes from other organic acids. K i t h classical procedures, this would require a t least one extraction prior t o t h e derivatization step. Even if t h e specific pentafluorobenzylation of phenols and acids reported by Davis (7) mere to be used, t h e analytes would still have to be isolated from t h e matrix, thus requiring a n extraction step with subsequent evaporation of solLent. Furthermore, the derivatization step itself would require additional workup. The specificity of the present procedure suggests the possibility t h a t phenols can be directly and specifically extracted and derivatized from physiological matrix in one step. The present d a t a also suggest t h a t bs controlling the reaction conditions, different phenols can be extracted and derivatized.
LITERATURE CITED 0. Gyllenhaal, H. Brotel, and P. Hartvig, J . Chromatogr.. 129. 295-302 ( 1976), H. Brotell. H. Ehrsson, and 0. Gyllenhaal, J . Chromafogr , 78, 294-301 (1973). H. Ehrsson, Acta Pharm. Suec., 8, 113-118 (1971). A . Arbin and P. Edlund, Acta Pharm. Suec., 12, 119-126 (1975). A. J. F. Wickramasinghe and R. S. Shaw, Biochem. J . , 141, 179-187 (1974). F. A. Fitzpatrick, M. A. Wynalda, and D. G . Kaiser, Anal. Cbem.. 49, 1032-1035 (1977). B. Davis, Anal. Chem., 49, 832-834 (1977). J, Dockx, Synthesis, 441-456 (1973). R. A. Jones, Aldrichim. Acta, 9 (3), 35-45 (1976). E. V. Dehmlow, Agnew. Chem. Int. Ed., 13, 170-179 (1974). C. M. Starks, J . A m . Chem. Soc., 93, 195-199 (1971). C. M. Starks and R. M. Ownes, J . A m . Chem. Soc., 95, 3613-3617 (1973). A. W. Herriott and D. Picker, J . Am. Chem. Soc.. 97 2347-2349 (1975). J. E. Gordon and R. E. Kutina. J. Am. Chem. SOC.,99, 3903-3909 (1977) B. Lindstrom and M. Molander, J . Chromatogr , 101, 219-221 (1974). B. Lindstrom and M. Molander. J . Chromatogr , 114, 459-462 (1975). J. A. F. de Silva and I. Berkersky. J . Chromatogr., 99, 447-460 (1974). H. Ehrsson and A. Tiliy, Ana/. Lett.. 6. 197-210 (1973). J. M. Rosenfeld and V. Taguchi, Anal. Chem., 48, 726-728 (1976). J. M. Rosenfeld, V. Y. Taguchi. B. L. Hillcoat, and M. Kawai, Anal. Chem., 49, 725-727 (1977). J. Rosenfeld, Anal. Lett., 10 (12), 917 (1977). J. Rosenfeld, B. Bowins, J. Roberts, J. Perkins. and A. S. Macpherson, Anal. Chem., 46, 2232-2234 (1974). J. D. Daley, J. M. Rosenfeld, and E. V. Younglai, Steroids, 27, 481-492 (1976). The Merck Index, 8th, Merck & Co., 1968, p 422.
RECEIVED November 18, 197'7. Accepted January 23, 1978. This work was supported by the Medical Research Council of Canada by Grant MRC-GOO7 and by a grant from IBM of Canada.
Influence of the Sample Position in Compensated Scanning Calorimeters Stanislaw L. Randzio' and Stig Sunner" Thermochemistry Laboratory, Chemical Center, University of Lund, S-220 07 Lund, Sweden
A theoretical analysis is made of the influence of sample position on the measured signal in compensated scanning calorimeters (DSC). Equations are derived and block diagrams are constructed for two configurations of the calorimetric cell. It is shown that the signal measured is equal to a thermal signal generated in the sample only under the conditions that the investigated sample is inside the compensation feedback loop and the gain of the amplifier is sufficiently high. When the sample is outside the feedback loop, the signal measured depends also on the time constant of the sample and the heating rate, even if the gain of the amplifier is very high.
Differential scanning calorimetry (DSC) has found broad quantitative applications in measurements of chemical purity, heat capacities, enthalpies and temperatures of transitions. kinetics of condensed phase reactions, etc. Of the two scanning calorimeter techniques available today, heat flux DSC and power compensated DSC, the latter is worth special attention 'On leave from the Institute of Physical Chemistry, Polish Academy of Sciences, PL-01-224 Warsaw 49, Poland. 0003-2700/78/0350-0704$01 O O / O
because this technique is. in principle, better adapted for calorimetric measurements of good accuracy. In DSC measurements. large quantities of experimental data can easily be collected using a n automatic d a t a acquisition system. However, the interpretation of such experimental data is not straightforward which is apparent from the literature u h e r e one can find considerable discrepancies among results reported (1-3). Many papers are devoted t o an analysis of possible causes of these discrepancies. Some papers deal with heat exchange conditions between t h e calorimetric cell and t h e sample (3-5). In others the authors t r y to make a general theory of scanning calorimetric measurements ( 6 , 71, analyse the baseline problem (8-10). study the influence of particular instrumental properties ( 7 , 1 1 , 12) and t h e kinetics of transitions investigated (13). In the papers cited above, man! suggestions have been p u t forward on how to correct t h e obtained experimental information in order to get more precise results referring t o t h e chemical a n d / or physical process(es1 studied. Some of the papers deal with the construction of the calorimetric cell ( 1 1 , 14). Main suggestions are t o design a system with as small a heat capacity as possible and with a maximal heat transfer between t h e sample and t h e calorimetric cell. However, it is evidently not always possible t o c' 1978 American Chemical Society
