depends of course on the molecular weight of the compound and the number of fluorine atoms present. Generally, the quantity of sample required is of the order 0.' 50 mg. Functional Group Analysis. Procedures for the quantitative determination of fluorine funct'ionality are essentially nonexistent. Chemical methods are not generally applicable because of the inertness of the carbonfluorine bond and the lack of specific group reactions. Although fluorinated organic moleculea exhibit intense infrared spectra, thej- are very complex in nature and assignment is difficult. I n addition, the transition probability of each group varies from molecule to molecule, necessitating a knowledge of the identity of compound in which the group resides. I n the case of protons the number of functional groups which can be deter-
mined by S M R spectrometry is small because of the difficulty in isolating the desired peaks. However, the chemical shifts in fluorine spectra are considerably greater than with protons and this problem is greatly 'minimized. Table VI presents the quantitative analysis of three of the more common functional groups for fluorine. From the results in Tables IV, T', and VI it can be seen t,hat the modified base line stabilizer and integrator combined with the modulation coils operated at 15,000 c.p.s. is capable of reliable peak intensities for fluorine resonance. The modified fluorine circuit was also applied to the determination of prot,ons and was found to operate satisfactorily for the few compounds studied. ACKNOWLEDGMENT
The authors gratefully acknowledge the help of Seymour Parter of the
Department of Mathematics, Cornel1 University, for deriving a solution for some of the equations. LITERATURE CITED
(1) Bloembergen, A. N., Purcell, E. M., Pound, R. Y.,Phys. Rev. 73, 679 (,1948 ) . ( 2 ) Giulott, L., Chiarotti, G., Cristiani, G., J . Chem. Phys. 22, 1143 (1954). (3) Johnson, L. F., "NMR and E P R Spectroscopy," Chap. 15, Pergamon Press, London, 1960. (4) Jungnickel, J. L., Forbes, J . W., AXAL.CHEM. 35.938 11963). ( 5 ) Nederbragt) G. I?., Iteilly, C. A , , J . Chem. Phys. 24, 1110 (1956). (6) Reilly, C. A,, ANAL.CHEX 30, 839 (1958). ( 7 ) Shoolery, J. N., "SMR and EPR Spectroscopy," Chap. 8, p. 132, Pergamnn Press, London, 1960. (~, 8 ) Williams. R. B.. Ann. S. Y. A c a d . Sci. 70, 890 (1958): RECEIVED for review August l5> 1963. Accepted May 13, 1964. Research supported by the National Science Foundation as Grant S o . S S F G-15550.
Determination of Active Hydrogen by Nuclear Magnetic Resonance Spectrometry PAUL J. PAULSEN' and W. D. COOKE Baker Laboratory, Cornell University, Ithaca, N . Y .
b A proposed method for quantitative determination of active hydrogen is based on the exchange! reaction of the group with heavy water and the determination of the exchanging protons by NMR spectrometry. The proposed method is nondestructive, more precise than conventional methods, and can b e applied to less reactive groups such as acetylenic hydrogen and CHZCOgroups. Completeness #ofthe exchange reaction is not usually required for the quantitative determination of the active hydrogen.
T
HE DETERMINATION of active hydrogen is widely used by organic chemists for a varief y of purposes. Conventional method< are generally based on the chemical reactivity of the grouii to a variety of reagents. One of the more common mc3thods involves reaction with methyl Grignard reagent and the subsequent volumetric measurement of the evolved methane after com1)letion of the reaction l'he preciqinn of the method (3%) 1' such that the 1)rocedure can onlj be classified as semiquantitative ( 4 ) . Other methods 1 Present address, Nrttlonal Rurpau of Standards, IVashingtnn, I).C.
involve the reaction of the active group with lithium aluminum hydride, with the subsequent volumetric determination of the evolved hydrogen gas ( 5 ) X different approach has been used by Harp and Eiffert (1) in hhich the active hydrogen groups were allowed to exchange with a large excess of D 2 0 The intensity of the OH absorption band a t 2.97 microns mas used to deteimine the amount of hydrogen exchanged I n this method it is necessaiy that a large enough excess of D20 be uied so that essentiallj all the active hydrogen ai)pears in the nater molecule In the proposed S M R method this requirement is usually not necesbary. l'he chemical methods have the disadx antage of being applicable only to highlj reactire groups such as alcohols, amines, phenol- etc The proposed method on the other hand has better preciw~n is nondestructive, and can be applied t o a wider ranqe of group reactii ity The propoied method is similar to the conventional methods in that it alco depends on the quantitat i r e determination of a product of a reaction inlolvinp the active group In thi. ea-e the reagent molccule is heat-) ~ a t e and r the measured product gives riie to a merged peak in the 60-
Mc./second KMR spectrum resulting from proton exchange. Whenever a sample contains two different types of protons which rapidly exchange places between the two sites, only one signal, representing the combined areas, is observed. The resultant peak occurs a t an appropriately weighted position between the two original peaks ( 3 ) . If) for example, an alcohol is mixed with D20, the D20 exhibits no S M R signal a t 60 l I c . / second and the single peak resulting from the exchange process contains all the active hydrogens regardless of whether they reside in the water or the alcohol. In the proposed method, the protons in this peak are quantitatively determined and used as a measure of the active hydrogen present in the sample. I t should be emphasized that a quantitative transfer of the active hydrogen to HDO is not required. An equilibrium dist,ribution of the protons between the active site and D 2 0 will yield a single N l I R peak containing all the active hydrogen. l'hr course of the reaction of heavy water with a group containing an active hydrogen can be illustrated by equations such as the following typical reactions:
RKHz
+ 2DzO % RKD2 + 2HD0
VOL. 36, NO. 9, AUGUST 1964
1721
+ D20 R O D + H D O + DzO e RC C D + H D O .CH,COCH, + 6 D z 0 e ROH RCECH
%
CDsCOCDa
+ 6HD0
The determination of the protons in the merged peak (the active hydrogenwater peak) is possible by a procedure previously described in which the area of the peak is compared to the peak area of a known amount of a n internal standard (2). The radio frequency power level must be kept low enough to avoid errors attributable to different degrees of saturation of the nuclear spin states. This is accomplished by measuring the relative peak areas a t different power levels and decreasing the level until no further change in ratio is observed ( 2 ) . Active hydrogens are defined on the basis of their reactivity in subst’itution reactions or, from an analytical point of view, on the basis of their reactivity with methyl magnesium bromide, lithium aluminum hydride, or other reagents used for their quantitative determination. With deuterium exchange, essentially any working definition of “active” may be chosen by varying the length of time over which exchange ca,n occur and by use of different catalysts at varying concentrations to increase exchange rates. This flexible definition of “active” hydrogens is illustrated by the fact that the protons in acetone can be determined by exchanging them with D20 in the presence of a LiOD catalyst. EXPERIMENTAL
The method requires a homogeneous liquid phase and preliminary work might be necessary in some cases to find a solvent which will accommodate the sample, heavy water, internal standard, and catalyst. Fortunately, most compounds containing active hydrogens are reasonably soluble in polar solvents. For the compounds studied, acetonitrile or pyridine was used when a solvent was required. If necessary, the water peak can be identified by the addition of a
Table I.
small amount of H20 to a separate sample and noting which peak increases. In situations where other peaks overlap the H D O peak, it is possible to make use of solvent effects to shift the position of the water peak-Le., by changing the solvent-to-heavy water ratio of the mixture. The choice of internal standard will depend .on the compounds being analyzed ( 2 ) . For purposes of calculating results it is necessary to classify the exchange reactions as fast or slow. Those exchange reactions which occur rapidly enough to give only one peak for both the exchanged and unexchanged protons are classified as fast. I n this case the peak area represents the total active hydrogen content regardless of the amount of DzO added to the system. For slow exchange the active hydrogens appear both as a water peak and a separate active hydrogen peak and measurement of the water peak does not, give the correct answer in this case. However, with knowledge of the initial deuterium content and the amount of active hydrogens exchanged, an H I D ratio in the water can be calculated. (This is assumed to be the same ratio that exists a t the active hydrogen site). From this information the total active hydrogen content can be calculated. I n the case of slow exchange it is necessary to allow the system to come to equilibrium to facilitate the area measurements. Otherwise, the water peak will be increasing as the exchange proceeds, rendering precise area measurements difficult. The classification of the exchange rates as fast o r slow is not always obvious by inspection. In case of doubt they can be distinguished by observing the spectrum of the compound to be determined with and without the addition of DzO. If, on adding heavy water, a peak (or peaks) completely disappears from the spectrum, the exchange is “fast.” If the peak only partially disappears, the exchange is slow. If there is still some doubt as to the exchange rate, the safest procedure is to add a 50-fold excess of DzO to drive the reaction to completion, and treat the exchange as fast. For both fast and slow exchanges it is necessary to make corrections for the proton impurity of the heavy water and
Determination of Active Hydrogen in Organic Compounds
No. active hydrogens per mole Theoretical Found 1 1.00 3 3.04 3 3.07 2 1.92 2 2.00 2 2.02 2 2.04 2 2.01 2 2.06 1 0.95 6 5.89
0
b
Error, Sample Rate % Methanol Fast 0.0 +1.3 p-Aminobenzoic acid Fast 2-Aminoethanol Fast +2.3 -4.0 1,3-Butanediol Fast Diethyl malonate” 0.0 Slow Ethyl acetoacetate0 Slow +1 .o Acetamide Slow +2.0 Resorcinol Slow +0.5 ResorcinolQ Fast +3.0 -5.0 Phenylacetyleneb Slow -1.8 Acetoneb Slow Catalyst, pyridine. Catalyst, LiOD dissolved in DzO (prepared by dissolving lithium metal in D20).
1722
ANALYTICAL CHEMISTRY
in addition, for any water impurities present in the original sample, if this correction is desired. Calculations. For the case of fast exchange, all the active hydrogens will appear in the merged active hydrogen-HD0 peak. This is true regardless of the completeness of the exchange reaction and of the amount of heavy water present. After correcting the area of this peak for a n y H D O present in the DzO, and knowing the number of moles of proton in the internal standard, it is possible to determine the moles of exchanged protons directly from the peak area ratios ( 2 ) . The calculation for slow exchange is complicated by the fact that the amount of unexchanged protons must be determined in addition to those exchanged. This can be accomplished by the following equation: Moles of active hydrogen =
where : A = Total moles of hydrogen in the water peak after exchange as determined from the peak area ratio times the gram equivalent of protons in the internal standard. B = The quantity A corrected for the moles of proton originally present in the DzO = the amount of H (and D) exchanged. C = Moles of deuterium added to the sample. H / D ratio in water = A / ( C - B ) If a sample contained both slow and faPt exchangeable active hydrogens the above equation is not applicable. In this case the best course of action would be to use a very large excess of D20 and neglect the corrections. If the ratio of deuterium available to exchangeable hydrogen mere 50, the error would be only 2y0 for ignoring slow unexchanged hydrogens if all the hydrogen were slow. For cases where part of the exchangeable hydrogens were fast, the error would be less than 2%. RESULTS
The method has been applied to a variety of different types of active hydrogen and the results are shown in Table I. Concentrations of the active compounds were about 2.V. The compounds tested were purified and dried by conventional procedures, and where feasible, assayed for purity by gas chromatography. The purity of the compounds determined by gas chromatography was of the order of 99%. In general the choice of solvent. internal standard, and catalyst will depend on the particular sample being analyzed. Such factors as rates of exchange, miscibility, and spectral overlap must be considered. The samples were prepared by injecting the materials into a capped serum vial and noting the increments in weight.
Although the results shown in Table
I are reported in the number of moles of
standard were exchanged, an average error of 1.6% was obtained.
active hydrogen per mole of compound, it would be also possible to determine the weight per cent of active hydrogen in the sample. Omitting the results for phenylacetylene where it was found that some of the protons of the internal
(1) Harp, R'. R.,Eiffert, R. C., Ax.41,. C H E V . 32, 794 (1960). D., 1bid.j ( 2 ) Paulsen, P. J., Cooke, 1713 (1964). (3) Pople, J. A , , Schneider, IT. G., Bernstem, H. J., "High Resolution Nuclear
LITERATURE CITED
Magnetic Resonance," p. 218, LIcGrawHill, New Tork, 1959. ( 4 ) Siggia, Sidney, "Quantitative Organic Analysis via Funct,ional Groups," p. 41, I$-iley, Sew Tork, 1049. ( 5 ) FYild, F., "Estimat'ion of Organic Compounds," p. 64, Cambridge University Press, Cambridge, 1953. RECEIVED for review February 24, 1964. A4cceptedMay 13, 1964.
Chronopotentiometry and Chronoamperometry with Unshielded Planar Electrodes PETER JAMES LINGANE Division of Chemistry and Chemical Engineering, California Institute o f Technology, Pasadena, Calif.
b It is shown exp'erimentally that the chronopotentiometric and chronoarnperometric constants obtained with unshielded, circular, planar electrodes satisfy the equations
and
Therefore, it is desirable to extrapolate the experimental value to the rl" = 0 or the t 1 i 2 = 0 intercept in careful analytical work.
SINCE
the Sand equation
and the Cottrell equation
are strictly applicable only to conditions of one-dimensional linear diffusion, shielded planar electrodes have been employed in accurate chronopotentiometric ( 2 ) and chronoamperometric ( 7 > (7, I O ) esperiment;i. Bard ( 2 ) has coniliared shieldd and unshielded electrodes and ha. observed that the chronopotentiomrtric constant increases a t long values of the tran:ition time only in the case of unshirlded electrodes. His result; -upgrst that th(3 chronopotentiotnrtric cwnstant obtained with an unsliieltlcd planar disk electrode has the sainr qualitative dependence on the trnniition time as tha,t obtained with a sj)licricnl clcc,trode. 'I'hc puq)c)sc of this paper is to obtain a qunntitntix-e experimental description of the chronopotention.letric and chrono-
amperometric constants obtained with unshielded planar disk electrodes. The chronopotentiometric constants under conditions of one-dimensional cylindrical ( I S ) and spherical (12) diffusion can both be written in the form of the Sand term times a power series in ( D T r 2 ) 1 ' 2 . Similarly the chronoaniperometric constants under conditions of one-dimensional cylindrical (3) and spherical (3) diffusion can be written in the form of the Cottrell term times a power series in ( D t t r 2 ) 1 ' 2 . -4lthough the unshielded disk electrode is a two-dimerisional diffusion problem, we have nonetheless attempted a correction term in the form of a powers series in ( D T r 2 ) l r 2 or (Dt,'r2)liZwhere r is the circular radius of the planar disk electrode which we employed. The D and t dependence were determined explicitly and the r dependence was assumed on the basis of intuitive and dimensional arguments. I t is shown that only the square root term contributes to the correction. Therefore, the nonlinearity of the diffusion field about unshielded, planar, circular electrodes can be corrected for by extrapolating the experimental values of the chronopotentiometric and chronoamperometric constants to the T ~ = ' ~0 or the t 1 ' 2 = 0 intercept. EXPERIMENTAL
The chronopotentiometric setup was usual. The constant' current was obtained by putting large dropping resistors in series with a 270-volt battery bank. A Clare mercury wetted, makebefore-break, d.c. relay was used for switching. -4 Philbrick P2 differential amplifier was used as a follower. The constant currents were determined during the experiment since currents measured prior to the tvqicrinient (when a dummy resistor is sub5tituted for the cell) were about 0.3% greater than those observed during the experiment.
The i - t curve was displayed on a Sargent-SR recorder; the chart was driven at a rate of 12 inches, min. by a synchronous motor. The transition times mere measured directly from the chart paper by the method of Kuwana (14). The chronoarnperometric experiments employed 2. Kenking T K potentiostat (Wrinkmsnn In*trumenti, Inc., Cantague Road, Westbury, S . IT.), and the current was determined bv measuring the iR drop developed resistor. The Sargent r with a 5-mv. range plug., was used to monitor this current continuously. h jacketed, single-coml of about 125-m1. capaci ployed. The Teflon cap \v openings for the various nitrogen inlets, for the salt bridge, for the reference electrode, and for the working and auxiliary electrodes. The wlt bridge n-as of the cracked glass type. The raxiliary electrode was not placed in a wp-.rate compartment because it was desired to kerp the rest potentials of the auxiliary and working electrodes identical; the ninke-before-break relay, used in the chronopotentiometric circuit to minimize current transients, momentarily shorts these two electrodes together and hence undesired electrochemistry takes place if these two potentials are not identical (I). The cell was stirred with a magnetic stirrer and deaerated with "prepurified" nitrogen. So attempt was made to slioc~kniount the cell. The cell was therniost,atetl at 25.0 = 0.1" C. The electrode emliloycd in this study was a Beckman S o . 39273 platinuni button electrode. The projected area was determined to be 0.2088 0.0004 sq. crn. by measuring mutually p r i m dicular diameters with an optical comparator. -4s received, the electrode surface was dull in color anti dceply scratched; therefore, it way polishrd with 4, 0 emerl- paper and cleaned with aqua regia prior to its initial u i e . The electrode was mounted horizontally in the center of the cell and oriented so that the diffusion was ul)wards. The auxiliary electrode was positioned par-
*
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* 1723
