A gronp of the papers resented a t the Fister Award Sym ium Honor ing Philip f i i v i n g , Division of Anal tical Chemistry, 137tc Meeting, American Chemical SoCleveland, Ohio, ~ ~ % l S s O Other . papers from this symposium will be published later.
Fisher Award Symposium
Organic Analysis: Art and Science PHILIP J. ELVING Department of Chemistry, University of Michigan, Ann Arbor, Mich.
b Organic analysis, similar to any other area of analytical chemistry, involves the application of our knowledge of the chemical and physical properties of substances to their characterization, identification, and determination. Its origin i s lost in prehistory, when it was first utilized to satisfy that curiosity of man which has always been a driving force in the development of science and technology. Throughout the history of chemistry, organic analysis has fluctuated between the empirical approach to analytical problems and the attempt to develop and use rationally conceived analytical methods. Today, much of organic analysis i s still largely empirical in nature. One must recognize the tremendous contribution to the development of organic analysis of those artists in chemistry, past and present, who have been able, in effect, to outdistance available knowledge and to solve analytical problems by brilliant technique. On the other hand, this success i s no reason for failure to explore constantly the scientific basis of analytical methods with the twin objectives of their improvement and of their eventual replacement by better methods. With our increasing knowledge of fundamental chemical and physical properties, a more scientific approach to the solution of difficult analytical problems i s possible. An analytical method whose scientific basis i s not clearly understood i s always a potential source of difficulty.
T
TREMENDOUS CHANGES that havc occurred in analytical chemistry during the past 20 years havc aroused great enthusiasm in analytical chemists and have caused them to feel that not only is analytical chemistry developing a t a rapid rate, but that it is
HE
1538
ANALYTICAL CHEMISTRY
also progressing with unstoppable impetus toward more and more better things. However, a moderately searching survey of the situation indicates that there is still much to be done; that analytical chemistry is not in the satisfactory state in which we might believe it to be. For one thing, analytical chemistry is certainly not yet as highly regarded as analytical chemists would like to have i t be. One need only look at such phenomena as the decrease in courses in analytical chemistry offered in many universities and the tendency of nonanalytical chemists, both in academic institutions and in industry, to regard analytical chemistry as, a t best, a somewhat necessary evil. That much of contemporary analytical chemistry is excellent can be taken for granted. Consequently, the present discussion is devoted not to praising analytical chemistry, but to examining it and, more specifically, organic analysis, and to stating some personal views on what difficulties there are and on n h a t might be done to lessen them. The principal difficulty seems to be that there is still too much art and too little science in organic analysis. FUNCTION
AND
NATURE OF ANALYTICAL CHEMISTRY
dnalytical chemistry is not in itself a primary area of chemistry, but is rather a derived area. It is important that we recognize this and its service function. The purposc of analytical chemistry as an area of science is essentially the development of approaches for satisfying the curiosity of man regarding the compositional nature of materials. As a means of satisfying this curiosity, analytical Chemistry is not only indispensable to chemistry, pure and applied, but is also of impor-
tance in all areas of science and technology, as well as in many of the humanities and social sciences such as archaeology. The goal of analytical chemistry is information for a purpose. This carries the implication of the unimportance of the information-seeking technique used, provided that it enables the desired knowledge to be obtained with the necessary degrees of specificity and accuracy. Consequently, it is encouraging to note that by now the discussions are decreasing regarding the relative or absolute virtues of instrumental us. noninstrumental methods, of wet us. dry methods, of micro us. macromethods. In analyzing a substance, that approach should be used which yields the desired information in the most efficient manner within the specified limits of accuracy. We need generalize concerning the merits of techniques only if such generalizations are appropriate to the objectives of analytical chemistry-e.g., it is commonly recognized that methods based on the measurement of physical properties are usually more rapid than other methods, whereas those based on chemical reactivity are more precise, and those based on a spectrum type of measurement are more selective. l h i s is not always so-e.g., acid-base titrations are quite rapid, and often quite selective. Definition of Analytical Chemistry. We might then start t o define analytical chemistry on the basis of the operational definition given by Kolthoff (11): “The aims and objectives of analytical chemistry are to determine the composition of any simple or complex compound or mixture of compounds.” I n order to implement this statement, one can develop another definition of analytical chemistry, which is the underlying basis for the present discussion: Analytical
chemistry is the scientific application of the chemical and physical properties of substances to their identification, characterization, and determination. De&ition of Organic Analysis. Definition of organic analysis is more difficult. For one thing, the differentiation of organic from inorganic analysis is rapidly becoming less distinct. Formerly, inorganic analysis stressed elemental analysis in terms of ionic species as obtainable in aqueous solution. Now, however, the analyst of inorganic material uses more and more the general approach of the analyst of organic materials: determination of ‘elements, of functional moieties, and of compounds as compounds, often on covalent complex molecules. Consequently, one might simply classify organic analysis, operationally, as being the analysis of materials in which carbon compounds constitute the matrix and of compounds in which a covalent carbon skeleton is the principal functional unit. This allows one to include the determination of inorganic species which are often found in organic samples and which are legitimately part of organic analysis. NATURE
OF
ADVANCES I N CHEMISTRY
ANALYTICAL
The fact should be emphasized that fundamental discoveries in analytical chemistry are as few and as far between as elsewhere in science. Much research in analytical chemistry is concerned with the development, elaboration, and modification of past work. Too frequently, “new” methods, which appear with great fanfare, turn out on subsequent, more detailed examination to be the resurrection of old methods with more or less modification. For example, many a new method announced for the determination of fluorine in organic compounds is actually the combination of an old method, perhaps slightly modified, for decomposing fluorine-containing organic compounds and converting the fluorine to fluoride ion, with a known procedure for determining fluoride ion which has not yet been estensively used with this particular decomposition method. Really new ideas of analytical chemistry should involve a fundamentally novel and superior way-e.g., of solving a pressing problem; of adapting a heretofore unused technique of separation or of measurement to analysis; and of elucidating the nature of a process, chemical reaction, or physical technique used in analytical chemistry and thereby enabling a significant improvement in its applicability. Most new reagents proposed in the literature do not fit the foregoing definition as can be seen by the relatively few of these which survive as a permanent
part of the armory of analytical chemistry. A good example of reagents which have survived is, of course, the Karl Fischer reagent and of procedures, which seem destined for survival, the Schoniger oxygen combustion technique. This discussion regarding the relative paucity of fundamentally new discoveries in analytical chemistry and the predominantly developmental aspects of much analytical-chemical research is not to decry the value of the improvement of existing analytical techniques and methods. This is what most of us do and what most of us probably should do. The purpose of the discussion is merely to caution the analytical chemist against thinking that an analytical problem has been solved, when the situation has been only slightly ameliorated. Let me make clear a t this point my admiration for and my appreciation of the great men of organic analysis from Lavoisier on to the present day, through such chemical giants as Chevreul, GayLussac, Thenard, Liebig, Dumas, Dennstedt, Pregl, and the many others. One must recognize the tremendous contributions to the development of organic analysis made by these artists in chemistry, past and present, who were able and whose successors are able, in effect, to outdistance the available knowledge of their time and to solve analytical problems by brilliant intuition and by masterful technique. However, this success-and contemporary organic analysis is on the whole quite successful in answering the questions asked of it-is no reason for our failure to recognize that much of organic analysis is still largely empirical in nature and for our failure to explore constantly the scientific basis of analytical methods, with the twin objectives of their improvement and of their eventual replacement by better methods. With our increasing knowledge of fundamental chemical and physical properties, a more scientific approach to the solution of analytical problems is possible. Analytical chemistry will advance as a truly scientific area only to the extent to which analytical chemists are willing and are able to investigate the fundamental bases of their analytical techniques, methods, and reactions. The current importance and necessity for critical research and development in analytical chemistry are due to the fact that the implementation of analytical chemistry as a problem-solving technique has to a considerable extent outdistanced our knowledge of its theoretical bases as a science. The early and immediate success of many an analytical approach when first used has often tended to obscure the fact that our real knowledge of the applicability and limitation of the method or technique was slight. Sooner or later, this has
resulted id difficulty and, occasionally, in the discard of a method which could have been of great service if it had been adequately investigated when first proposed. Rationally conceived and developed analytical methods are a necessary goal. An analytical method whose scientific basis is not clearly understood always contains a potential source of trouble. SCOPE
OF
ORGANIC ANALYSIS
The analyst of organic materials is customarily confronted with four types of problems: establishment of elemental and functional composition, determination and proof of structure (characterization), establishment of identity (qualitative analysis), and determination of purity (percentage composition). As a result of the rapid development and increasing complexity in recent years of industrial chemical technology and of fundamental chemical investigation, the demands made on the analytical chemist have increased noticeably from the viewpoints of time, precision. and selectivity. It is frequently necessary to allow only minutes for analytical work, where formerly hours or even days would have sufficed; the precision demanded has usually increased markedly; and, as far as selectivity is concerned, one need merely recall the complicated mixtures of related compounds which have to be analyzed in the petroleum and other organic chemical industries to realize the magnitude of the problems that confront the contemporary analytical chemist. A typical example arises from the production during the past two decades of stable fluorocarbons, with a concomitant need for more accurate fluorine determinations as the fluorine content of the organic compounds increases. As the synthesizer tries to make increasingly more stable compounds, he has demanded that the analytical chemist analyze them more and more rapidly, and more and more accurately. At the present time, the organic analyst is able to cope successfully with the problem of the decomposition of the organic compound; there is little doubt that existing techniques enable us to decompose fluorine-containing compounds to within one part in a thousand. The difficulty is in the still unsatisfied need for an accurate method for determining fluoride ion once it has been obtained. The problem, obviously, is then one oi inorganic rather than organic analysis. To meet the demands made of him, the analytical chemist has available not only the large number of classical tools of analytical chemistry, but also the greatly increased number of means of separation and of measuring previously unused molecular, atomic, subatomic. VOL. 32, NO. 12, NOVEMBER 1960
1539
and nuclear properties which havc become available in the past two decades, plus the increase in our knowlrdge of the chemical and physical properties of substances. One need only cite two or three approaches to indicate the impressive catalog of analytical techniqurs which have been added in recent years: radiant energy absorption over a large section of the radiant energy spectrum, columnar multistage srparation as in ion eschange and gas chromatography, and titration in nonaqueous media. ORGANIC ELEMENTAL ANALYSIS
I’:lcmental analysis is customarily done for one of three reasons: to determine the empirical composition of a new compound, to confirm identity (the relation of analytical precision to the effect of a congrner present as impurity is one which is not often sufficirntly examined by the analytical chemist), and to determine a functional group via the dekrrnmation of an element present in the compound only as a part of that group. The latter, important application is due to the fact that elemrntal analj& is usually more accurate than functional group analysis. The accuracy of the latter is limited either by the equilibria prevailing in the chrmicd reactions employed, or by the unccrtainty in the measurcment of a physical property such as photometric transmittancc or faradaic currrnt. The magnitude of the problcm for the organic analyst seems at first glance much less than that encauntcrrd by thr inorganic analyst, sincc of thc 104, more or less, rlements, the analyst of organic material eommonly dctrrniinc~s only four or five and rarely more than trn of the group consisting of carbo% hydrogen, nitrogrn, sulfur, oiygru, chlorine, bromine, iotlinc, fluorine, and phosphorus. The difficulty enrountcrcd in prartic.e by the organic analyst in drtcrniining his few rlrments arises from t h r more stable fmni in which clcnients arr bound in organic. eompounds. ?‘he inorganic analyst is frequentfy ronc*ernrtl with the determination of ions which 3re nvaibblr to him upon simplr dissolution of t h r samplr in watcr. ‘rhc organic analyst, on the 0th hand, has usully to uw a variety of chrmical reactions, oftcn under drastk csonditions, in order to obeah the simple ionic or other sprcivs which ean br mcasuml. Morrovor, the problrm is inrreasing in c*ompl(~ity; the number of elements which thc organic. analyst is callrd upon to determine is incrrasing significxntly-c.g., silicon has nom bccome a coitstitwnt of an important class of organic rompounds. One might suinmarizc the fundamental problem in organic rlcmentul anal-
154
ANALYTICAL CHEMISTRY
ysis as the need for methods which convert a n elrment with 100.0 & 0.1% yield to a readily mrasurcd form and which make minimum demands upon the analyst. (One can safrly gcncralizc that analytical method is bcst, which rcquires the Irast skill and thc least time of the analyst, other things k i n g equal.) Obviously, the previous discussion has been concerned with the chemical reactivity methods uscd for elcmrntal analysis. These, interestingly, arr often a combination of problems in chemical engineering arid inorganic gas analysise.g., the three stages in the dctermination of carbon and hydrogcn by cornbustion: high-tc>mpcraturc vapor-phase and hrtrrogrncous solid-gis phase osidation of thr compound and its decomposition products, purification of the stream of carrirr gas and products, and analysis of thc gas strram for selected components which, in this cast’, are water and carbon dioxide. Tho organic analyst gcnrrally uses only a few simple types of chrmi~al destruction methods in clemcntal analysis--e.g., osidative combustion, prrosidc osidation, solution oxidation, and alkali metal reduction-thrsc arc followvctl by specific end-point detmnination methods for thr tliffcrrnt rlcmcmts. Thc carbon-hydrogcn tnrthod is a good rsanipl(b of diligrnt tlcwkqmt~nt with no mi1 frinrlainont:il (&hang(.for ovrr a crntury. l‘he osporinwnt:rl arrangcnirnt :tntl c~ntitlitionsof s:rml)le and apparatus sixr, timr. os\-gc~nflow rate, agents addc~lto purify tliv g:is stroam, mrans of :ibsorbing H20 : i t i d ( ‘ 0 2 , c t c . , h a w hcrn altcrrrl, but, tliv prinviplr of high lxmprraturc osithtion with c’opim osidr and osygcn rrm:iins u t d t m ~ d . Thr mrthod is an rranipl(~of I)oth tlic skill and thr consrrv:itinii of tlw org:iiii(* analyst. As C‘on~in ($1 has I)ninttd out, Prrgl rrt,ainr(l I(wl tlio\itlr i n tliv cwnbustion tubv for rvnioving nitrogcm osidrs i w n though Sands ant1 otlirrs lrad quitr rlrarly tlunonstratrtl the difficulty of rquilibratitig Iratl tliositk. \vith tht. vxtrr vapor i i i :I gnsrous :itmosphwr around it. A pcmonal cspc,ricmw is u w t h rcblating txwiusr it typificbs :In attitutlv which hopc~fully is now tlkippc~:~ring.The first paper prrsrnktl hj- the, witor a t an .4mcriran Clicimicd Socirty mtsrting was at thr 1941 mwtiiig i n St. Louis and dralt with ;in rxtcwxil nirans of removing nitrogrn osidcs i n tlicl carbonhydrogrn dctrrniination. A4sh(B rntcrcd the inwting room in which I 1 0 was to sl>eak, he mrt a wc4-knon-n organic microanalyst who rrni:irkrtl that he would go in to listrn to thr papcr but that he knrw that it \vas of littl(5 merit, since, if it worc a gootl nirthotl. it would havc brrn applied by Prrgl. 1r.t u s rrndcr all tiur homagc, to Liebig and to Ek.gl, but Ict 11s a t the Same tinie acknowldgc, a t least as a
A s c v d line of dcvc~lopmcntinvolves inc~asurc~mcntmcthods which depend ripon thc properties of atoms as affected by their chc~micalmatrix and which will, ac~wrdingly,permit the determination (Jf t~lrirwnts :is functiorial (intitics in org:inic: compounds--t>.g., nuclear magnc:tic* rwonanw. Evwy cluncnt in an orgaiiic compound fulfills :t cwtain function and is consequently a functional group; in many cast’s it is desirable to tliffercwtiatc among, e.g., primary, swontiary , and tertiary hydrogrns in a caompouiid. ORGANIC FUNCTIONAL GROUP ANALYSIS
A fuiictional group might bc ddined as :in atom or group of atoms which forms :I rccwgnizablr segmont of an organic compound or which fulfills a tlrfinahlc function in tc’rms of reactivity or a measurablc physical propc.rty-e.g., trrtiary hydrogc,n, alcoholic hytlroxyl, and (molizablc carbonyl. Any hond of a covalont ixtturc b e t w e n two elcments (mi bc c,onsidtired as :t functional grouping. 1 hc: mc:isurcmt.nt of organic functiowility is of primary importanc~:in drtcsrniining thc, irlrntity, structure, and purity of org:mic* compounds. The tlctormination of struvturc at the present timt, is largoly prcdic8:ited on being able to c&in:itc> the, typos and amounts of diffcwnt stwctural moietics in the mol(~culv. Similnrlj-, identity of a substyicc is bmt c&il)lished by ascertaining tlw functional groups present in rcqwct to nature antl rclativck amount. ‘I’hv nuin1)c~rof c:ommonly dctcrmined fuiictiorinl groups was formerly rclativdy small, h i n g limitcd by thc ability of t h c an:ilytic*:tl chr,mist to dcvisc chrmi c x l rcwtions with yiclds iii ( w c s s of 95y0. (‘l’hci clificulty of obtaining stoic~1iionic~tric~:~lly compl(~tct rcwkions is so ~ ( ~ 1c~stablishcd 1 as a working postu1:itc. in sjmthrtic organic chemistry that it is highly rornplirncntary to the analytical c~lic~inistthat his ability to obtain 98 to 1 0 0 ~ oyields for his rcactions is acwptrd without undue comment.) However, with thr increasing notd (or ticsir(.) to mcasurc mort: and inor(> typm of organic. functionalities, rr(wursr has had t o bc in(wasing1y made to such spectrum tccshniqucs as infrarcd al)sorption, Idarography, and mass spctctronic%ry. It is more than a pleasantly philosophiral q u t d o n as to whethcr :in incartxscd drinanci for organicit1 functional analysis has promoted the use of thcsc. techniques or wh(>thrr t h r availability of the techniques, with thrir possibility of determining such functionality, has resulted in thc incrcascd demand for the determination of thc functionalities. 1 he future will set:, as already montioncd, increased c~nphnsis on the I
r 7
.
analysis of a compound in terms of the sprcific functional nature of the elcmcmts in t h e compound. At the present time, infrared absorption spwtrophotomctry and nuclear m a g n h c resonance arc the most frequently uscd approaches to this problem. Determination of Compounds as Compounds. At the present time, rigorous identification and determination of cornpounds as compounds, rathcr than in terms of t h e elemental composition and functional group moieties prcsent, arc possible only in the rase of solids, where measurcment of the proper tic,^ of the unit crll of the crystal allows rctrogriition of a compound as a unique and specific chemical individual. Such crystallographic mrasuremcnts can he made by x-ray diffraction and petrographic microscopy. Polymorphism, whirh owurs occasionally among organir compounds, provides the only situation whcrc a pure chemical individual can exist in moro than onc crj~stallinc form, each with differing crystallographic propcrtics. A less rigorous approach, which is also applicable to liquid and gasrous phases, uses an effert tluc to thc behavior of tho molerule as a \vhole- r~atlilyavailable, the tl(tcmiination or organic, rompounds as individual units instclad of as synthwrs of scparatclly tl(tcrniincd parts will b t farilitatcd. RESEARCH IN ORGANIC ANALYSIS
The follo\ving discussion roiisists of personal itlras rcgarding soiii(: siwcific typc>s of iiivc.stigation in organic: an:tlysis, 1vvhic.h inrrit attwtion in acatl(tinic institutions. Whilr basic. ivoi-k in :inatlyticbal chcmistry is bring doli(: in acad(~mic~, industrial, :inti institutional organizations (at timos it sccxins th:it the: groatcr a m o u n t of organic analytical research comos out of industrial labtrrntoriw), the s i t u h o n s arc sufficic~ntly diffrrc.nt t o inakc it \vortIiivliil(~ to cmphasizr thc t y p w of problrms w1iic.h acadtmicians should pursur’. I t will sufficc to singlc out nic~roly four such typc9 : D(wlopnwnt of fund:tnic~ntttlly nrw approacht~s to analytically important situations. ’I’h(1sc approaclicss should
include rvactions, techniques, and procedures. The importance of such activity is (imphasized throughout this papc’r. Study of the behavior of mixtures of substanws. Onc? of the fundamental problems in analytical chemistry is that of interfrrence. The nonanalytical chemist, when he studies the properties, chemical and physical, of materials, usually investigates t h a n for the pure substances. Howcvcr, when the analytical chrniist conies to apply thcsct properties, he is draling with mixtures of varying degrees of complexity, in which nonidcal behavior is genwally the rule rathor than the exception, and in whirh thc chcmicd cmvironnicnt plays an important role. Onc need rrf(.r only to surh phenomena us pressure broadening in infrarcd absorption spectrophotomc%ry, cmtrainnirnt in precipitation, and induced reactions in titrirnctry to emphasize thr: importance of studying thc behavior of misturcs. Krscarch in analytical chemistry is oftrn the refinemcnt of our kno\vledgc of the cheniical and physical propcrties of substances whcn applicd to misturcs of t h m substances. bkploration of the fundamentals of analytiral apprwac*hrs. This Ivould inrlude invrstigation of the basic throry ant1 phmomcna whicali :irv cwx)untcred in analyticnlly usvful tcdiniquc.s of separation and of nic~asun~nic~nt, including cluc*idation of thr nic~c~hanisms and writrolling factors in :rnnlj-tically important rcactions. ’Thv \vciltling togcthcr of p l i j s i c d mc~asurcinc~nt:tiit1 c.hrniicd rcwtivity in ortlor to (~xtrntlthc :innlytic.al applicxbilitj. of suc,li tii(~:isureiii(,iit,. The anal\%ic*:ilchomist frcyiwntly owrlooks thr possibility of grc~ttly:iinplifying thc applic~aI)ilityof ii ~ ~ h y s i c ~ a l ~ ~ t ~ c ~ofl i i i i q u c moasurc~nwntby tloing a little proliminary cahcsniistry o n th(b surnplv. Carbon-Halogen Bond Fission. The results of a n approach of the type i n d i c a t d can be illustratctl by t h e systematic investigations which niy collaborators and I h a w niatle in recent years on the nature of dectrochcmical ca,rbon-li:tlogc~n hond fission in org:tniv conipountls. It. has bcen possible to :~pl)lythc rcmlts of thcsc studios in scwral arcas of organic analysis, emphasizing thc proposition that analytical mc.thotls are most readily developc~i wlicm kno\vlcdgc~ of the fundamc.iita1 chcinicd and physiral propcrtim involvotl is :tvaiIabk~: Polai.ogr:iphic* tl~~tc~rrniti:itioti of many indivitlual liaIog(~iiat~(~l org:inic. conipounds of :i 1:trgr varicty of tyl)c’s, :ts \vcll as in sonic ws(%s,thv idtbntificxtion o f thc1 cvmpounds. I’olarogmphir :in:ilJ compounds tlitTc.ririg in tl(sgrec of halogrnatioii-r.g., rlc.tc.rniiii:itioti of the individual c*omponc.nt,sof n misturcx of thc c:hloroaLc-(tiv acitls (S). A.5 a wsrilt of t h c study (5) of thc b:isic* li~-tlrolytic antl c~loctrochcmic.aI twhnvior of the t h r w inclivitlual wl:itivc>ly unstablc
VOL. 32, NO. 12, NOVEMBER 1960
1541
chloroacetaldehydes, i t was possible to develop a method for polarographically analyzing mixtures of them when present with the parent compound, acetaldehyde (4). Polarographic analysis of mixtures of compounds with different halogen substituents-e.g., analysis of a sample containing chloro-. bromo-. and iodoacetones Polaroerauhic analvsis of mixtures of homolog&; halogenited compounds, if the half-wave potential values differ significantly. I n this connection, i t is important to emphasize study of the effect of nature and composition of the test solution upon measurable properties, since it is often possible by varying the background electrolyte to separate properties which otherwise are not individually measurable.
TIO).
An example of what might be done analytically when sufficient information is available, is the possible analysis of a mixture of the racemic and meso @,a'dibromosuccinic acids. These acids could be determined by first reducing them electrochemically at a massive mercury electrode at the proper pH; the meso acid is entirely converted to fumaric acid, whereas the racemic acid is converted to a reproducible mixture of maleic and fumaric acids (7). The resulting solution can then be polarographed at a pH which will allow separation of the maleic and fumaric acid waves. This is actually a chemical method of analysis, since the focal point in the procedure is not the polarography, but the chemistry involved in the meso and racemic acids forming different products on electrochemical reduction. Effect of Experimental Conditions. One of t h e important requirements in developing a method in organic analysis is the thorough investigation of the effects of experimental variables upon the response of the species being separated or measured. This is particularly true for so-called physicochemical methods for analyzing mixtures of related compounds, as illustrated by a case from our experience: the analysis of mixtures of the isomeric cis-trans acids, maleic and fumaric. The early literature is quite contradictory as to whether or not i t is possible to analyze polarographically mixtures of the two acids (16). A systematic study of their behavior revealed two reasons for the conflicting reports, one related to the behavior of the acids and the other to an artifact of measurement; recognition of these two factors led to a simple and satisfactory procedure for analyzing mixtures of the two acids (6, 16). The more fundamental effect has to do with the variation of the half-wave potentials of the acids with p H (Figure 1) (9). I n the acid region the potentials are much too close together to permit any resolution of the polarographic
1542
0
ANALYTICAL CHEMISTRY
PH
Figure 1. Variation of polarographic half-wave potentials with pH ( 9 ) 1. 2.
Maleic acid Fumaric acid
waves. However, the waves can be readily resolved in alkaline solution. The accentuation of the difference in the half-wave potential beginning at p H 6 is probably connected with the chelated structure possible only in maleic acid in the p H region where existence of the monoanionic species are expected. The other point which would be trivial, if i t had not been the cause of confusion in the literature, is simply related to the geometric properties of polarographic waves-eg., Figure 2. While the slope of a wave for a given species in a given medium is generally quite reproducible and independent of concentration, the potential range subtended by the wave from its toe to its limiting current is proportional to the concentration of the species. Thus, the maleic and fumaric waves are quite readily resolvable at concentrations of 10-4 to 10-3A4; at concentrations exceeding 2 X 10-3M, the two waves fuse. METHODOLOGICAL PROBLEMS IN ORGANIC ANALYSIS
Micro a n d Macro Methods. One cannot discuss organic analysis, apparently, without saying something concerning micro and macro methods,
Table 1.
Polarography as a Micro Technique
Analytical Test Solution Concn. of Mass of electroactive Electroactive Volume, species, Species ml. mM Present, h1g.n 20 2
0.5
0.1
1.0 0.02 0,00005
0.05 0.01 (1 drop) a Calculated on basis that molecular weight of electroactive species is about 100.
including semi and ultra. Today, each new analytical approach has to prove itself on a micro basis. One wonders occasionally whether this bespeaks an overwhelming need for micro scale techniques or whether this demand, at least in part, is merely a result of inertia or habit. For years, organic elemental analysis has been largely identified with micro scale techniques. This identification has been accompanied by much study and development, with resulting improvement in the methods used. However, as already discussed, there has been relatively little that is fundamentally new. The fact should not be overlooked that the now classical techniques of radiant energy absorption and of polarography are basically micro scale techniques, and are frequently classifiable as ultramicro techniques in respect to their requirements for the amounts of sample necessary and of constituent being determined-e.g., consider the amount of material needed in polarographically measuring a functional group or compound (Table I). At the present time, there is an interesting and growing factor in microanalysis involving not only the analysis of small samples, but the determination of very low percentages, often in very small samplcs; this is truly trace analysis. The success of analytical chemists in determining materials in the absolute range of 10-8 and less grams a t concentration levels of 10" and less has been impressive. Contemporary trace analysis presents a terrific challenge to the analytical chemist in respect to its demands for selectivity, absolute sensitivity, and concentrational sensitivity. In-line Analysis and Instrumentation. The growing importance of continuous in-line methods of analysis is apparent; the methodological demands of such analysis call for considerable imagination upon the part of the analytical chemist. Since the approaches to the problem are being exhaustively discussed in the current literature, there is no need to consider them here; rather, I would like to discuss a more basic problem of attitude, which is of considerable importance in the teaching of analytical chemistry. The subject of continuous analysis logically leads to a consideration of instrumentation and instrumental analysis. The latter term is one about which I have never been quite satisfied, since I am never clear as to what is meant. Apparently, instrumental analysis means all things to all chemists. To many, it seems to denote all methods of measurement except that of mass and volume, and all methods of separation except precipitation. Textbooks on instrumental analysis discuss, inter alia, such things as extraction, ion exchange,
and chromatography, which are not methods of measurement but of separation. One is a little perplexed at the idea that a glass tube with a stopcock at one end and filled with a solid chemical, into which the sample is p o u r 4 for interaction, is more of an instrument than a n exactly analogous tube, called a buret, and filled with a chemical solution, which is poured into the sample for interaction. Instrumentation, on the other hand, is something of which I think all analytical chemists must approve as the imaginative attempt to use our knowledge of optics, electricity, magnetism, electronics, mechanics, and other branches of science and technology to facilitate the utilization of chemical and physical properties for analysis. Typically, analjdical methods should be instrumented for three general types of obj ectives : Instrumentation usually enables US to measure properties more readily, generally more rapidly, some times more precisely, and often more selectively. Instrumentation permits the measurement of properties which previously were not usable by the analytical chemist or a t least were not readily available to him. Instrumentation tends to minimize the requirements for analyst skill and time. This effort to economize is a note-
worthy one. However, it will not result, as some people seem to fear, in replacement of the analytical chemist by a group of black boxes. Rather, the trend would seem to be that instrumentation results in the replacement of less skilled operating analysts by instruments, which, in their turn, demand much more highly skilled and imaginative analytical chemists to devise the basic procedures and to arrange the situations to which the instruments can be and should be applied. Moreover, the availability of the means of answering questions heretofore unanswerable or of answering old questions more rapidly serves to stimulate the asking of more difficult, more numerous, and more demanding questions for the analytical chemist to answer. Among interesting recent developments in instrumentation for organic analysis, two specific developments should be singled out. The recently developed automatic apparatus for the Dumas nitrogen determination apparently conserves time and to some extent skill on the part of the analyst. However, its being limited to compounds which burn satisfactorily emphasizes the need for a fundamental investigation of the determination of total nitrogen with the goal of formulating a more pervasive method of getting a t the nitrogen.
Figure 2.
proach should be used on a specific problem? Should he attempt an optimal combination of separation and measurement techniques, or should he attempt to use the best available specific method of measurement? What sequence of methods will yield the most data with the least effort? What are the relative virtues in a specific case of chemical methods us. physical methods us. physicochemical methods? For example, at the preeent time there is the apparently overwhelming superiority of gas chromatography as a spectrum technique for identification and measurement. Should all organic functional group and compound analysis be restricted to gas chromatography? The problem is, unfortunately, not so simple that the previous question can be answered meaningfully. Gas chromatography, like many other currently available spectrum techniques, is excellent, once the procedure for a specific type of mixture has been developed. It is not convenient for the occasional user, nor can i t yet handle all types of mixtures. Based on past history, i t is safe to predict that gas chromatography is and will continue to be a most useful item in the armory of the analytical chemist. However, it will not solve all problems nor will i t completely replace other
Variation in polarographic current-potential curves for mixtures of maleic and fumaric acids (76)
Background electrolyte. 1M NH&l with NHd added to pH 8 2 5 6 3 4 Curve No. 1 2 0 7 Maleate, mM 1 3 0 4 0 7 07 13 20 Fumarate, mM 04 0 7 07 13 13
Contrasted to this method for the determination of total element, there is nuclear magnetic resonance which permits selectivity in determining the different types of an element in regard to functionality. At the present, the use of nuclear magnetic resonance spectra for analytical work requires considerable time, skill, and cost; considerable development is necessary before it will be analytically satisfactory. Selection and Integration of Analytical Techniques. One of the difficult'problems facing the contemporary organic analytical chemist is t h a t of the optimum utilization of the currently vast armory of analytical chemistry. What technique or ap-
7 20 20
separation techniques such as distillation and paper chromatography. I n turn, gas chromatography will at some future period be partially replaced by newer techniques, of whose nature the present writer is unfortunately not yet aware. Expression of Analytical Results. An analysis is not completed until the analytical data obtained are expressed in such a manner that the person, for whom the results are intended, understands their significance as compositional indices in respect to the problem for which the analysis was requested. This throws a twofold burden on the analytical chemist: conversion and expression of the analytical data in the VOL. 32, NO. 12, NOVEMBER 1960
1543
most usoful form and terms; and esplicnit iiielic*:ition of thc. rdiability of the :iii:iIytiwl data iii torms of indiws of piw-isioii. ‘l-lio :lliaIyst should c\~aluatc~thc n i c y t l i o t l \vliich hc usrs in regard to Its c w i i f i t l c w e ~ limits. Any given set of :iii:ilyticd iwults m:ty br diveargent bec*:iusv of :i varicty of offcc*tsand causes. I t is iiiiportniit to know what chance is boiiig takrii iii any specific analytical procct1ui.o t l u t thc rcsults obtained are iiicoriwt-i.c,., art,uaIly beyond a cert:iin range. wound thc objective or true Y:llric~.
In roporting tlic pcwcntsgr of nitro:I sample as 8.34%, it is more Iidpful both to the analyst and to the pcmoii for whom the data have been obtaiiiwl to csprrss the results in terms having tlio follo\ving meaning, “There arc 98 chanccs in 100 that the nitrogen content’ of tlic sample submitted is in tliv r:ingo of 8.34 i 0.12%.” Education in Analytical Chemistry. 1~:elricutioiii n ana1ytic;il clicmistiy is today a ~ ~ r e s s i n problem g and one \vlii(ali is vcry closely related t o tlic sc*icwtific*:ippro:ich t o organic analysis :inel, intlcccl, to analytical chemistry i ii p ~ i i ( ~ i , : i I . ’I‘iwr~~is :i growing indication of a mor(% rigorous sciciitific. attitud(. in :iii:il~~ti(~il vlii~inistryaiitl to analytical prol~l(~nis - rg..the. f‘rcyurntinvlusion in : i ~ i : i l ~ ~ t i c ~ papvrs :il of good discussions, w l i ( v x ~sii(~11 tr(xtnwnt is justified, of the I)liJ.sic*:il p i i i r c i ~ ~of l e the, ~ tcdiniqws and iiicxtliolls w(d, of tlicx nic~c~h:uiisins of tlic e : l i c ~ n i i ( ~ : i li,c,:ic*tioiiscmliloycd, and of tlic. fiiii(1:initxt:il ~)i~iiiciplc~ und(dying tlrc. pi~olY~llllrc~ tl(~vc~1opc”l. ’ l l i i ~c ~ n i ~ ) h m ini ~riirrcmt hmc~ricaii :icxel(Bniic, rcw:ii,cli i n :iiialjtical rhebmistry is r ~ i it l i t y stutly of tlic tlicwotical :iii(i pi,:ii~tic:ilt’~iiirl:imc.iitals of chc~micd ant1 1 ) l i J . , k i t x l l)inp(~tic~s :iii(I lx~liavior, an(1 of i i i ( , : i ~ i i i . ( ’ i ~ i t , i i t : i n d sc,par:ition tc~cliiiiqut~s.\ v l i i t , l i s t w x ’ :is tlic basis of :in:ilj+wl inc~tiiotl.;,i x t l i e i i , t1i:in on the t l ( ~ v i h p i n c ~ i iof t i i i i : i l J t i ( x l pi’ocwlurcs I. per sr. lliis i.; I):isc~l on tiles bdic>f that, n i i c ’ c t tlw f~iiicl:iiiic~nt:ilprinciples li:iv(> h i i c~t:il)lialic~l. t h c s :in:ilytical mc~tliorl.e’:in iisii:iIly tlicm br tl(w~1oped nioro ixl)i(lly :iiitl xitishctorily. I~iifoi~tiiii:itc~l~~. :ill iloc~i:not wciii to 1 ~ \. \ ~ ~ 1i 1n :inal\~tic~il c~licmisti~y in acatl(~niic~ institutions. ‘I’l\t~rcis tlrr tlistrcwiirg f ’ ( ~ ~ I that i n ~ tlica c.urric.ulum ant1 coiirsths i n :inalytic~:il c~lic~inistryh:ive not kcyt u p with tlir t l c tlw toa(~1iingof ot,licr : i i ’ ( w of c~hoinistrj~. Onc nwtl only (*it(’the symptom that \\.lien tn.o tcnclirrs of analjticd cht’mistry start to discuss the topic, “\Vliat do you tcarli in your course in clcniont,:try quantitative analysis?,” tlicy almost inevitably list the 1:iboratory csprrinients which R ~ Cinc~ludetl in the coursc rather th:m the topics of the lecture or class discussion. gcii in
1544
ANALYTICAL CHEMISTRY
Our courses in analytical chemistry are still too frc.qurntly built around the laboratory esperinients, with the lecture serving primarily to ?.;plain thew espcrimtbnts, rather than the other way around-that of tlie laboratory esperimrnts being used to illustrate some of the points covered in the classroom. This attitude is largely the result of the historical fact that courses in analytical chemistry fifty and more years ago had as their primary function the training of young chrmists in the technique of analytical chemistry in the hope of making them into skilled analysts. Today, the first course in analytical chemistry should and must convey to students the scientific bases for the scopc’, mcxthods, limitations, and methodology of analytical chemistry. The emphasis must be on training thcorcticians in analytical chemistry, not technicians in applied analysis. The replacc,mcmt of old expcrimcnts in gravimetry and titrimetry by “black box’’ csperiincnts in instrumented analytical approaches docs not cope with the fundamental problem of presenting analytical chemistry as a scientific discipline. CONCLUSIONS
In cnoncluding this plea for a still morc scicntific approach to thc problems of organic analysis, I want to emphasize again the iniportanvc of iiirratigation in three arcas, which arc wtually important in all of analytical clicmistry. First, in t l i c y tl(~vc~lopnic~iit of analytical tc.chniquc~s-]ihysi(~al and c ~ l i u n i c d for sep:ir:ttion anti iii(,:is~ir(~iiic~nt, the analyticaal clic~mistmust I)(\ on the (annstant alert for iicw apl)rouchc~s. He must k w p i n mind th:it any phj.siic,:il or cheniicxl property ? : i n 1 1 usrti ~ for qu:ilitativc ide.ntificotion, cpintitativv nie:tsuremcmt, or both, if tlw 1 ~ r o p i ~is t y or can b ( x made sl)c.i,ifica cmough for the purpose at hand. ‘ l h :in:iI~tical?hemist must be (:v(’r rcntl!. to :i~)plytcchniquw basctl on c~lic~niic*nlreactions, pIij.sic*:rl properties. or fundamcwtal prinriplcs \vhicah hcrrtofore c,ithrr were not used in analytical chemistry or found minimal use. He must undertake niorc pmctrating csploration and utilization of known tecahniques. Secondly, tlie analytical chemist must attempt to tlrwlop in explicit form the mcthodology of analyticxl c~licniistryin the direction of forniulnting rational approarhi~sto analytical problems in both rcwarcli and practirc. Unkind physicists h n v ~mor(. than OIICC charactcrizctl muc,li of annljtic.al chemistry as “npplie~l witc~hu-aft.” To answer that “it,” nicxning :in nnnlytical procedure, works is not an ans\ver. One must bclicvc that i n a scientifically developed and rntionally applied analytical mcthod, better results will be ob-
tained with less labor. Furthermore, the analytical chemist has an obligation to enlarge the area of scientific chemistry; he can’t merely live upon it, enjoying the fruits of the labors of other chemists. Thirdly, in the development of specific procedures for solving the problems of compositional determination, the analytical chemist must be both critical and imaginative in his attitude toward the adaptation and utilization of techniques. There is an urgency to combine the results of intuition, based on experience, with an efficient use of a fundamental knoivledge of chemistry, The analytical chemist, organic or inorganic, must, in toto, be a scientist as well as a solver of problems. The analytiral chemist must, above all, beware of complacency. Great needs still exist in analytical chemistry and the analytical chemist must constantly strive to meet them. The latter he can do best-in the opinion of the prrsent writer-by precise attention to the underlying chemical and physical fundamentals of analytical chemistry. If we do so, we can with confidence paraphrase Browning with some slight modification and gross poetical violation : Come grow old along with me The best in analytical chemistry is yet to be. LITERATURE CITED
(1) Cheni. Eng. News 38, ?io. 15, 58 (April 11, 1960). (2) Corwin, A. H., 97th Meeting, ACS, Rochester, K. Y., September 9, 1937. (3) Dennstedt, M., in J. Houben, “Die Methoden der organischen Chemie,” 3th ed., Vol. I, pp. 109-23, Georg Thicme, Leipzig, 1925. (4) Elving, P. J , Bennett, C. E., ANAL. CHEV.26,1572 (1954). (5) Elving, 1’. J., Bennett, C. E., J. Electrochem. SOC.101, 520 (1$)54). (6) Elving, 1’. J., Rosenthal, I., .\SAL CFIERI. 26, 1451 (1954). ( 7 ) Elving, 1’. J., Roscnthal, I., IIartin, A. J., J . A m Cheva. SOC. 77, 5218 I1 R5.5 \ - . . - - I .
(8) Elving, 1’. J., Tang, C.-S., ANAL. Cmhf. 23, 341 (1951). (9) Elving, P. J., Teitelbaum, C., J . A m . Chem. SOC.71, 3916 (1949). (IO) Elving, 1’. J., Van Atta, R. E., ASAL. CHEhf. 27, 1908 (1%5). (11) Kolthoff, I. M., Chem. Eng. ’Yews 28, 2882 (1950). (12) Lee, T. S., Meyer, It., Ami. Chinz. 4 c l a 13, 350 (1955). ( 1 3 ) Martin, A. J., Ileveraux, H., A s a ~ . CHEM. 31, 19:32 (1959). (14) ter llleulen, H., Heslinga, J., “Nouvelles methodes d’analyse chimique organique,” 2nd ed., Ilunod, Paria 1932. (15) SchGniger, JY., IMikrochim. Acla 1955 ( I ) , 123; 1956 (4-6), 869. (16) \Tarshawsky, B., Elving, P. J., hlandel, J., ANAL. CHEM. 19, 161 (1947). RECEIVEDfor review May 16, 1960. Accepted May 16, 1960. Division of Analytical Chemistry, 137th Meeting, ACS, Cleveland, Ohio, April 1960.
