AnalyticaI Ion Cyclotron Resonance Spectrometry Acetylation as a Chemical Ionization Technique Maurice M. Bursey, Thomas A. Elwood, Michael K. Hoffman, Thomas A. Lehman, and Joan M. Tesarek Venable Chemical Laboratory, The University of North Carolina, Chapel Hill, N. C. 27514 Acetylation by chemical ionization at 13 eV and 25 ptorr represents a “soft” ionization process, where little excess energy is transferred to the ionized species. The acylating agents generated from the ion-molecule reactions of butanedione with itself are found by ion cyclotron double resonance (ICDR) to be butanedione molecular ion and an ion of mass 129 observed in the ICR spectrum. Different functionally substituted molecules were reacted with butanedione under ICR conditions; acylation by butanedione ions is most favorable in molecules containing heteroatoms with unshared electron pairs. THETECHNIQUE OF CHEMICAL IONIZATION maSS Spectrometry ( I ) derives from the production of ions by ion-molecule reactions in the mass spectrometer (Equation 1).
A-B+
+C
-+
A
+ B-C+
(1)
Many studies have been performed at high pressures (1 torr) of methane, where the principal reaction is proton transfer from the strong Bronsted acid CH5+,which is a major product (47 of the ion current) of ionization of methane under these conditions (Equations 2 and 3).
+ CHa CHS+ + M
CH4+’
+ CHI. MH+ + CH4
+ +
CH5+
(2) (3)
The product is then the conjugate acid of the species t o be studied. Recent studies on smaller molecules have been extended to larger systems of some medicinal interest such as the alkaloids (2, 3) with attractive results; for alkaloids, the stability of the protonated molecule, or quasimolecular ion, permits less fragmentation before mass analysis. Thus, it is often possible to determine the molecular weight of a n alkaloid easily by this technique, even when ordinary electron-impact mass spectrometry (Equation 4) M+e+M+’+2e
(4)
yields a molecular ion peak diminished because of rapid fragmentation t o stable units. Chemical ionization by protonation is, then, a soft ionization process, one in which the neutral species is ionized by a secondary process rather thah by direct electron bombardment, and the Franck-Condon Principle is not applicable. Since in most cases less energy is transferred t o the molecular ion, there is decreased probability that subsequent fragmentation will diminish the ion current corresponding to the molecular weight plus the proton. Under conditions where very little energy is available in the transferring species, processes that involve ionization by transfer of groups larger than a proton might be still softer, since large molecules are likely (1) (a) F. H. Field and M. S. B. Munson, J. Amer. Chem. SOC.,88, 2621 (1966); (b) F. H. Field, Accounts Chem. Res., 1,42 (1968). (2) H. M. Fales, G. W. A. Milne, and M. L. Vestal, J. Amer. Chem. SOC.,91, 3682 (1969). ( 3 ) H. M. Fales, H. A. Lloyd, and G . W. A. Milne, ibid., 92, 1590 (1970). 1370
t o have significantly lower ionization potentials and larger groups can absorb more of the energy released in the formation of the new bond by vibration than a proton can. If the energy of this transferring species could be decreased, greater selectivity could conceivably be induced in subsequent reactions. In general, most ion-molecule reactions which are actually observed are exothermic (4), and have little or no activation energy. A complication, however, results when reactions are studied which involve the transfer of larger groups: most of the molecules we have studied with a n eye toward application in analysis d o not simply transfer a group to the substrate molecule, but instead participate in several other competing reactions, both with the substrate molecule and with other molecules of their own kind. Hence the spectrum can become complicated, and it can be a problem t o sort out just those reactions which are the group transfers of interest. It is necessary, then, to have a way of analyzing the origin of peaks produced by ion-molecule reactions in such complex cases. At present, there are two important methods of doing this: tandem mass spectrometry (5) and ion cyclotron resonance (ICR) (6-8). Tandem mass spectrometers are not yet commercially available, but ICR spectrometers are. Ion cyclotron resonance allows the study of ion-molecule reactions at longer lifetimes of ions, as well as a t higher pressures, than conventional analytical mass spectrometry. The commercial instrumentation allows the analysis of ions at pressures from torr up to lo-* torr with ion flight times on the order of milliseconds [compare the conventional mass spectrometer, with a pressure range of from 10-8 torr to 10-4 torr (unless modified for high-pressure work) and a flight time of to 10-j secl. O n the millisecond time scale, pressures of about 10-5 torr are found to give satisfactory signals from products of ion-molecule reactions, the probability of one or two collisions per ion being fairly high in this range. At such pressures, the population of collision-stabilized species (AB+ in Equation 5 ) at any given time is low. A
+B
-+
AB+*
1
collision
AB+
fragmentation,
C+
+ Neutral
Once the AB+* intermediate has formed, the probability is low that a stabilizing collision t o carry off excess energy would occur in preference t o decomposition t o a n ion of lower mass and internal energy, with the excess energy carried off by the neutral species formed i n the decomposition. (In high-pressure mass spectrometry, such as chemical ionization mass (4) M. A. Haney and J. L. Franklin, J. Phys. Chem., 73, 4328
(1969). (5) J. H. Futrell and C. D. Miller, Reu. Sci. Instrum., 37, 1521 (1966). (6) J. L. Beauchamp, L. R. Anders, and J. D. Baldeschwieler, J. Amer. Chem. SOC.,89, 4569 (1967). (7) J. M. S. Henis, ibid., 90, 844 (1968). 41,22A (1969). (8) J. M. S. Henis, ANAL.CHEM.,
ANALYTICAL CHEMISTRY, VOL. 42. NO. 12, OCTOBER 1970
spectrometry, the probability is greater.) Consequently, products are usually formed by transfer rather than by sticking collisions in these studies. EXPERIMENTAL
Chemicals employed were the highest purity grade commercially available. The ICR spectrometer was a Varian ICR-9 Syrotron. The electron energy was low, 13.0 eV; this figure represents the sum of plate potential and trap potential. The ionizing current was 0.5 p A , and total ion current was usually 10-14 PA; a pressure of 25 to 40 ptom in the ICR cell, as measured by a VacIon pump used for ultimate pumping of the cell, provided this for samples. A ratio of close to 1 :1 of the compound studied and the ionizing species, butanedione, was employed. Cell voltages were low; typical values were: trap, 0.65 V; analyzer, split (9), 0.09 and 0.17 V; source, split (9), -0.16 and +0.30 V. The fixed frequency defined 100 gauss/amu; its rf level was 0.3 pA. The magnetic field sweep rate was 10 min, response 0.1 sec. Field modulation of amplitude 12.5 gauss was used. In ion cyclotron double resonance (ICDR) experiments, similar conditions were used. Pulse modulation (27 Hz, 0.05 V/cm output) was employed, and signals were monitored both in the source and in the analyzer. The conditions were similar to previously described conditions (6, 7).
86
64
129
1
107
Figure 1. ICR spectrum of a mixture of CH3COCOCH3 and CD3COCD3. Instrumental conditions are described in the experimental section
RESULTS AND DISCUSSION
An Example. As an example of the use of ICR and the advantages of the use of ICDR in studying chemical ionization through acetylation with butanedione, we show in Figure 1 the high-mass range of the spectrum of butanedione (CH3COCOCH3)and acetone-d6, recorded at a total pressure of 40 ptorr with equal contributions from each component to the pressure. The only peaks not shown in this trace are CH3CO+, m / e 43, from butanedione, and CD3CO+, m / e 46, from acetone-d6. The major peaks appear at mje 64 (molecular ion of acetone-de),86 (molecular ion of butanedione), 107, 110, and 129 (ion-molecule peaks). The origin of the ionmolecule peaks is not determined by simple ICR spectra. For their analysis, the ICDR spectra of the ion-molecule products are of great assistance. Selected regions of the ICDR spectrum of the mje 107 peak, for example, observed in the source (S) and the analyzer (A), are shown in Figure 2. They cover the regions m / e 45 to 49 (l), 63 to 65 (2), 83 to 88 (3), and 125 to 136 (4). The double resonance signals observed all point to a decrease in the production of m / e 107 when the precursor ions, mje 64, 86, and 129, are irradiated. Thus Equations 6-8 are suggested as
+ CH3COCOCHs CHaCOCOCH3+'+ CDaCOCD3 (CH3C0)s1 + CD3COCD3
CD3COCD3+'
+ +
+ C H 3 C 0 . (6) mje 107 + C H 3 C 0 . (7) m / e 107
+
mje 107
+ CHsCOCOCH3
1
v
4
3
2
Figure 2. Pertinent portions of the ICDR spectrum of m / e 107 in a mixture of CH3COCOCH3 and CD3COCD3. See text for identification of symbols
1
3
2
4.
Figure 3. Pertinent portions of the ICDR spectrum of m/e 110 in a mixture of CH3COCOCH3 and CD3COCD3. See text for identification of symbols
(8)
possible routes to the m / e 107 ion. The latter two reactions correspond to transfer of an acetyl ion, CH3CO+, from different precursors to the aCetOne-ds molecule. Similarly, Figure 3 indicates ICDR spectra of the m / e 110 ion in the source (S) and analyzer (A) covering the regions m/e 45 to 48, 62 to 65, 84 to 88, and 128 to 136. Only one ICDR peak is found among the sections illustrated, which suggests that the resonance is due to the process (9) T. A. Elwood, J. M. Tesarek, T. A. Lehman, and M. M. Bursey, 18th Annual Conference on Mass Spectrometry and Allied Topics, San Francisco, Calif., June 14-19, 1970.
+ CDaCOCD3
CD3COCD3+'
mje 110
+ CD3.
(9) and that butanedione is not at all involved in this process, even by charge-exchange reactions. Survey of Reactivities toward Acetylation by Butanedione. We have made a survey of the reactivity, under ICR conditions similar to those in this illustration, of common functional groups in the presence of butanedione, and have found that under a uniform set of conditions acetylation proceeds with compounds containing 0 and N to a moderate extent in the absence of any steric effects, but only marginally with the halogens, which are weaker Lewis bases. The +
ANALYTICAL CHEMISTRY, VOL. 42, NO. 12, OCTOBER 1970
1371
pressure range chosen (ca. 25 ptorr) emphasizes this difference, and use of low voltage (13.0 V) keeps the spectra relatively simple and easily comparable. All other conditions are very similar to those quoted for the examples given previously. Our eventual aim is to refine studies toward functional group analysis, and this report is our first step in that direction. In each case we have examined the acetylation of the functional group with ions produced from butanedione. This sort of reaction was chosen as a starting point because of the possible analogies in solution chemistry which might be used as a guide toward reactivity under acylating conditions. The actual molecule chosen as the acylating agent, butanedione, was selected because under the usual solvolytic conditions, it shows low reactivity toward most kinds of functional groups [except under the influence of light, when photochemical production of acetyl radicals increases its reactivity toward many species (IO)]. (Amines are a n exception here. I n such cases, the dual introduction system of the commercial instrument can be used to minimize reactions of neutral species.) Thus acetylated peaks can be ascribed t o ion-molecule reactions with some confidence, not t o artifacts. In addition, the mass spectrum of butanedione even a t high ionizing voltages consists primarily of the ions of mje 43 (CH3CO+)and 86 (CH3COCOCH3+‘),presenting a relatively clean spectrum for the study of ionic reaction products. Third, its ion-molecule mass spectrum contains a prominent m / e 129 peak, which is the m/e 129 observed in Figure 1. The origin of this ion is the reaction of butanedione molecular ion with neutral butanedione (Equation lo), CH3COCOCH1”
+ CH3COCOCH3
4
CH;COCO(COCHj)CH3+
+ CHyCO
*
(10)
as confirmed by double resonance (11). Since self-acylation is the only ion-molecule reaction of butanedione under the conditions of these experiments, the spectrum is relatively free for the study of cross reactions in mixtures of butanedione with other compounds. Reactivity of Hydrocarbons. The ICR spectrum of a methane-butanedione mixture under the conditions specified for the example (which hold for all compounds studied here) shows no peak corresponding to an “acylated methane” ion (mass 16 43 = 59); the only peaks that are not due solely to reactions of butanedione with itself occur at mje 72, 73, and 115. Since double resonance shows that the ion of mass 115 arises from precursors of mass 86 and 129, there is certainly reaction between butanedione and methane, but the sequence of reactions is far more complex than simple acylation (Equation 11).
+
CH,
+ CHaCOY’’ Y
=
Jt, CHKOCH,’
+Y
CHICO or CHBCOCOCH:,
(11)
If the alkane component of the mixture is n-pentane, a n “acylated pentane” ion might be expected at mass 115. An ion of this mass is present; double resonance indicates that ions of mass 86, 129, and 72 are precursors. It is small (2 % of total ion current), and a n ion of similar intensity may be found in the ICR spectrum of the methane-butanedione mix(10) J. G . CalVert and J. N. PittS, Jr., “Photochemistry,” John Wiley and Sons, New York, N. Y . , 1966, pp 421-2. The reaction is rapid; separate introduction of the components or use soon after mixing is required. (11) M. K. Hoffman, T. A. Lehman, T. A. Elwood, and M. M. Bursey, Tetruhedrorz Lert., submitted for publication. 1372
0
Table I. Reactions of Various Systems with Butanedione Acylated Compound product Zseca Precursors Hydrocarbons 59 ... ... 115 19 72. 86. 129 C2H4 71 ... ... Alkyl halides CHaBrb 138
