Chemical Ionization Mass Spectrometry of Complex Molecules Esters of Di- and Tricarboxylic Acids’ H. M. Fales, G. W. A. Milne, and R. S. Nicholson2 Laboratory 01 Chemistry, National Heart a n d Lung Institute, National Institutes of’Health, Bethesda, Md. 20014 The chemical ionization (CI) mass spectra of a series of esters of di- and tricarboxylic acids are reported. These derivatives, which are widely used as plasticizers and are difficult to identify by conventional electron impact (El) mass spectrometry, can be identified by CI mass spectrometry. Geometrical isomers such as diethyl maleate and fumarate can be distinguished readily from each other by CI mass spectrometry.
PLASTIC MATERIALS are commonly rendered flexible by the addition t o the rigid polymer of compounds of low molecular weight known as plasticizers. The result is a simple mixture from which the plasticizer can be leached by any solvent in which it is soluble. It is becoming increasingly clear that many materials such as blood ( I ) , milk (2), and cooking fat (3), t o name but three, are effective in removing plasticizer from the plastic containers in which they may be stored. The toxicity of the common phthalate plasticizers is considered to be rather low ( 4 ) , but a reliable method of identifying these compounds would be useful as a means of monitoring their transfer from plastics t o human tissue. This paper describes the use of CI mass spectrometry in this context. Mass spectrometry is now well established as a n analytical technique in organic chemistry ( 5 ) but there are certain areas where conventional E1 mass spectrometry is curiously unable t o distinguish between various related compounds. One such group of compounds is that made up of the esters of dia n d tricarboxylic acids, several of which are used very extensively a s plasticizers. Phthalate esters as a class can be easily recognized from their E1 mass spectra because, except for the dimethyl ester, they all give a very characteristic ion at mle 149, commonly considered t o be the protonated anhydride species (I, R = H). The protonated phthalic acid ion (11) at mje 167 may also be observed, as in the E1 mass spectrum of di(2-ethylhexyl)phthalate, but in the spectra of other phthalate esters such as di-n-butyl phthalate it is absent. Other ions such as the alkylated anhydride ion (I, R = alkyl) are also variable in intensity. Parent ions are invariably weak and often absent in higher homologs.
+
@ $ LcoR
I
The ion (I, R = H ) is so abundant and so characteristic of phthalates, the most common of the plasticizers, that mass spectrometrists have become accustomed t o equating a n unidentified ion at m/e 149 with phthalate impurities in the sample or in the spectrometer (6). This is a reliable enough correlation but it is totally without specificity and, indeed, specific identification of phthalate esters from their E1 mass spectra is difficult if not impossible because of the very low abundance of the other significant ions such as that at mje 207 ( M OC4Hs). Ions analogous to (I, R = H) are found in the E1 mass spectra of adipates (mle 129) and succinates (mle 101) and have similar diagnostic value. If C I mass spectrometry is applied to this problem, a differcnt picture emerges. Protonation of esters by the species CHSf and CnH5+ which are generated by E1 of methane at pressures of ca. 1 torr (7) has been shown (8) t o provide relatively stable protonated forms, or quasimolecular (QM+) ions. These QM’ ions undergo some fragmentation but a substantial proportion of them survive long enough t o be collected and so serve t o permit measurement of the molecular weight of the compound at hand. Transfer of a proton t o a base from the terr-butyl ion, giving isobutene, is a less exothermic process than transfer of a proton t o the same base from CH5+. Less fragmentation may therefore be expected t o follow protonation of a molecule by the tert-butyl ion and this is generally observed t o be the case. If the protonating species used is this tert-butyl ion, C4Hs+,formed from isobutane, the QM+ ion formed from a n ester is often the only important ion in its entire C I mass spectrum, particularly at low temperatures, e.g., 50-100 “C (9). EXPERIMENTAL All CI mass spectra were measured using methane o r isobutane as the reagent gas at 0.8-1.0 Torr source pressure a n d source temperatures between 100 and 300 “C as indicated. The mass spectrometer used was a n MS-902 (Associated Electrical Industries, Ltd. U. K.) equipped with the C I source described previously (10). All samples were admitted t o the source using a direct insertion probe. All samples were obtained from the “Chem Supply” collection, Model Number PLZ-150, Chem Service, Inc., P. 0. Box 15, Media, Pa., 19063, except di(2-ethy1hexyl)terephthalate which was prepared by the reaction of terephthaloyl chloride and 2-ethylhexanol.
aCrnH2 COOH
11
This is Part VI11 of a series. Part VI1 is H. M. Fales, Yumiko Nagai, G. W. A. Milne. H. Bryan Brewer, Jr., Thomas Bronzert, and John J. Pisano, Anal. Biocliem.. in press. National Science Foundation, Washington, D. C. (Guest Worker). (1) R . J. Jaeger and R. J. Rubin, Science, 170, 460 (1970). (2) J. Cerbulis and J. S . Ard, J . Ass. Offic. Anal. Clzem., 50, 646 (1967). (3) E. G. Perkins, J . Amer. Oil Cliem. SOC..44,197 (1967). (4) D. Calley, J. Autian, and W. L. Guess, J . Phurm. Sci., 55, 158 (1966). (5) K. Biernann, “Mass Spectrometry,’’ McGraw-Hill, New York, N. Y., 1962.
RESULTS AND DISCUSSION The E1 mass spectra of di(2-ethylhexyl) phthalate and di-nbutyl phthalate are shown in Figure 1. Although differences exist, the spectra are similar and de noco identification of (6) [bid., p 170. (7) F. H. Field and M. S. B. Munson, J . Amer. Cl7em. SOC.,87, 2289 (1965). (8) M. S. B. Munson and F. H . Field, ibid., 88, 4337 (1966). (9) F. H. Field, ibid., 91, 2827, 6334 (1969). (10) H. M. Fales, G. W. A. Milne, and M. L. Vestal, ibid., p 3682.
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
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'i'I
Table I. Isobutane CI Mass Spectra of Esters of Polybasic Acids: QM+ Ion Intensities
?
, ,
.,.,
. , . / . ? . 7 . T C
m
,I.,L
I
57
r.L&rlI1, 60
DI-+BL~YL
-
A
1
i, L. ,.L+.I-T 150 1
Im
P H T ~ P T F .E.I.
r
t
w r i
WE
m
I
.TI
M
I
I1
7 .
200
.
r- r
250
f
- 7 -
C/E
= ~78.
Figure 1. E1 mass spectra of di-(2-ethylhexyl)phthalate and di-n-butyl phthalate measured at 150 "C
either of these compounds from its E1 mass spectrum is, at best, a doubtful process. In Figure 2, the methane and isobutane CI mass spectra of di(2-ethylhexyl) phthalate are shown. In both CI mass spectra, which were measured at a source temperature of cu. 150 "C, a n abundant Q M + ion at 1) is observed. In the m ' e 391 ([.e,, molecular weight isobutane spectrum, there is very little breakdown of the Q M + ion but the fragment ions that d o appear are all found with higher abundance in the methane CI mass spectrum. Either CI mass spectrum would serve to identify the compound as a dioctyl phthalate, if not specifically the 2-ethylhexyl isomer, and the compound is therefore easily distinguished from di-nbutyl phthalate. This level of identification will be possible as long as the Q M + ion is relatively abundant. In fact, in all of the aliphatic and aromatic diesters whose isobutane C I mass spectra we have measured, none fail to give a n intense Q M + ion which, in all but a few cases, is the base peak of the
Compound Di(2-ethylhexyl)phthalate 391 87.5 Di(2-ethylhexyl)adipate 371 81 . O Dibutyl carbonate 175 93.2 Dibutyl succinate 23 1 72.6 Tributyl phosphate 267 84.5 Tributyl citrate 361 92.6 Diethyl maleate 173 69.6 Diethyl fumarate 173 66.1 Dibutyl tartrate 263 93.7 Triethylene glycol di(2-ethylhexoate) 403 9.3 Butyl glycolylbutyl phthalate 337 15.5 Di(2-ethylhexyl)isophthalate 391 13.1 Di(2-ethylhexyl)terephthalate 39 1 5.1 a The I3Csatellites of the Q M f ion are ignored in this calculation.
spectrum. In Table I are recorded the intensities of the QM+ ions of some of these compounds. The Q M + ions of these esters break down t o give three types of fragment ion. Thus di(2-ethylhexyl) phthalate gives four aromatic ions in its isobutane CI mass spectrum. These are 261 (2 a n d 149 (3 at mje 391 (100 %, QM+), 279 (2 Metastable ions are present indicating that both the ion at mje 279 and that at mje 261 are formed directly from the Q M f ion and thus the whole scheme of fragmentation could follow from protonation of the original molecule o n one of the oxygens as shown below:
z).
z), z),
+
+
+
m/e 391
m/e 279
m/e 391
m/e 261
-CO
1
i
I,'
I
m x,
mass spectra of di-(2-ethylhexy1)phthalate measured at 150 "C
IX
2 L
1
11
1XBUTR.E C
I
*--
tJ m 113
I*
S I
m
I,,, ,
1786
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
,
273
I
5
'Ot M
isophthalate measured at 150 "C 53 --
113
ISOBUTFN C. I . 60-
w
2
'0
--
These processes are similar to those previously observed in the CI mass spectra of esters (8) and they also parallel those observed in the E1 mass spectra of esters of phthalic acid (11, 12). The last remaining ion in the isobutane CI mass spectrum of di(2-ethylhexyl) phthalate is at m/e 113 and is presumed t o be the CsH1,+species. The isobutane CI mass spectra of di(2-ethylhexyl) isophthalate and the very similar di(2-ethylhexyl) terephthalate (Figure 3) are of interest since they confirm the structure of the above ions. Most noteworthy is the greater degree of fragmentation of the Q M + ions when compared to the Q M + ion of the phthalate isomer, suggesting that the cyclic ortho ester structure has considerable stability. The QM' ions at m/e 391 collapse to give only the noncyclic fragment ions at m/e 279 (11) F. W.McLafferty and R. S. Gohlke, ANAL.CHEM., 31, 2076 (1959). (12) C. Djerassi and C . Fenselau, J . Amer. Chem. Soc., 87, 5756 (1965).
s -i ?
and 167, the latter of which is not observed in the isobutane C I spectrum of the phthalate (ortho) isomer. O n the other hand, the cyclic ions at m,'e 149 and mie 261 are both absent in the isophthalate (metal and terephthalate (para) isomers. The difference is similar to, but more dramatic, than that observed (11, 12) in the E1 spectra of the phthalate and terephthalate esters. Similarly, di(2-ethylhexyl) adipate, in addition t o its Q M + ion at m,/e 371 (100%) has the analogous fragment ions at m/e 259 (873, 241 ( 2 7 3 , 129 ( 3 7 3 , and 113 In the isobutane C I mass spectrum of dibutyl succinate, the only fragment ion is found at mje 157 (25 %) and is formed by loss from the QM+ ion of C 4 H g O H ,a reaction analogous to the loss from the Q M + ion of di(2-ethylhexyl) phthalate or adipate of 2-ethylhexanol. The similarity of these spectra t o that of the phthalate, as opposed to those of the terephthalate and isophthalate esters, suggests that the aliphatic diesters
(2z).
c
40-
a99
I,,
211 ,
,
TRIBJTYL WEJ=WTE. M = 266.
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
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€.I.
are also stabilized by a cyclic form (ortho ester) upon protonation in the gas phase. Simpler esters give even less fragmentation. Thus tributyl phosphate, whose isobutane CI mass spectrum is shown in Figure 4, gives mainly three fragment ions at m/e 211, 155, and 99, which result from successive loss of three C4Hs ions from the Q M + ion. The same ions with greatly altered abundances are seen in the E1 mass spectrum of the same compound and extensive degradation to the protonated species H+(H3P04) m/e 99 is observed. It is noteworthy that, even under E1 conditions, the only ion observed in the molecular weight region is at m/e 267 and is the result of ionmolecule reactions. Dibutyl carbonate behaves similarly upon CI, giving a n ion at mie 119 (6%) as its only fragment ion. Dibutyl tartrate, in spite of its two hydroxyl groups, shows essentially no fragmentation of its Q M + ion at temperatures below 150 "C. The isobutane C I mass spectrum of tributyl citrate has only one fragment ion at m/e 259 (9 %) and this is formed by loss of C,HlnO?from the Q M + ion, possibly as below: CH,-COOC,Hg
-1-
HO-
P+
C- CO-0- C4Hg
I
I
I
accompanied by a single fragment ion at m/e 171 (1OOx). This ion is probably formed from the QM+ ion by a mechanism reminiscent of that involved in acyl migration reactions (14):
m i i
C7H15
+ I CH~-O-CH~CH~-OXC-C,H~~
-
I
I H
72.5
CHz-OCHzCH@COC7His m/e 403
I
O\ 0;
p/
CHzCHz m/e 171
Butyl glycolylbutyl phthalate, the common plasticizer BGBP, gives a more complicated isobutane C I mass spectrum (Figure 5). The Q M + ion at mje 337 (26%) loses C4H8, C4H100,or HOCH2COOC4HSto give the three major fragment ions at m/e 279 (27%), 263 (loo%), and 205 (38%), respectively. A metastable ion for the last of these transitions is observed. The final fragment ion, at m/e 149 (14%) is formed by further collapse by at least two of the three fragment ions, as indicated by the appropriate metastable ions. This scheme can be summarized as follows: +
&
COOH,
H CHz--COOC,Hg m, 'e 361
~ C m C H 2 C m C . H I
CHzCOOC4Hg
+ I HO-C
I CH,COOC,H,
+
:CO
+
C,HgOH
m/e 259
Such a process has not been observed previously in C I mass spectrometry but it is exactly the pathway by which acetone dicarboxylic acid is formed when citric acid is treated with concentrated sulfuric acid (13). The QM- ion in the isobutane C I mass spectrum of triethylene glycol di(2-ethylhexoate) is at m / e 403 (12%) and is
m/e 263
The isobutane C I mass spectra of diethyl maleate and diethyl fumarate, measured at 130 "C both consist only of a QM' ion at m/e 173. At temperatures above 250 "C how-
(13) R. Adarns. H. M. Chiles, and C. F. Rassweiler, "Organic
Syntheses," 2nd ed., Coll. Vol. I, H. Gilrnan and A. H. Blatt, Ed., John Wiley and Sons, New York, N. Y . , 1948, p 10. 1788
(14) C. Pedersen, Tetrahedron Lett., 1967, 511.
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
m/e 173
m/e 127
m/e 145
m/e 117
m/e 99
+
-
fmH2
121.5
C2HSOCO
m/e 173
+
*
f
COOHz
J
HOC0
m/e 145
ever, some fragmentation of these Q M f ions takes place (Figure 6) with results paralleling those of the phthalates a n d isophthalates. Thus, the Q M + ions of both diethyl maleate a n d fumarate lose ethylene in two successive steps by the hydrogen transfer processes postulated by Munson a n d Field (8) t o form the hemi- a n d diacid ions at mje 145 a n d 117, respectively, but the intensities of these ions (and the corresponding metastables) which require n o cyclic forms for stabilization, are much higher in the case of the fumarate than the maleate. O n the other hand, for obvious reasons, loss of ethanol t o give the cyclic ion at mje 127 is much more intense in the case of the maleate ester. Metastables support all these reactions in both cases. Electron impact spectra of the methyl esters of these two isomers would seem t o require a different interpretation (]I, 12) but a recent reinvestigation by Myerson (15) shows that, in fact, the differences observed in the E1 spectra of the compounds are entirely analogous t o the differences found in the E1 spectra of the phthalate and terephthalate isomers. I n t h e case of t h e C I spectra of the maleate-fumarate a n d phthalate-isophthalate/terephthalate systems, the cyclic alkylated anhydride ions (e.g., I, R = alkyl) are stabilized in the same way as are the corresponding EI-derived ions. This stability does not extend t o the odd-electron molecular ions in E1 where alkoxy1 cleavage results in somewhat less intense molecular ions in the maleate a n d phthalate spectra. In CI, o n the other hand, the Q M + ions from the cis or ortho isomers are more abundant, notably in the case of the phthalate, presumably because of stabilization ciu the cyclic ortho ester tautomers shown above. Loss of CO from the alkylated anhydride ion is observed only in the E1 spectra.
CONCLUSIONS Two conclusions may be drawn from this preliminary study of the CI mass spectra of esters of polybasic acids. First, protonation of these molecules can be achieved under extremely mild conditions with the appropriate reagent ion and source temperature. In this way, even the most unstable of the protonated species will survive long enough to be collected. Its mass can therefore be measured and the molecular weight of the material under study will follow. In many cases, this datum will be of great assistance in identifying the compound. Second, the breakdown that is observed to follow protonation of these esters follows the familiar rules of acid-catalyzed reactions. We have previously observed this tendency of (15) S. Meyerson, P. J. Ihrig, and T. L. Hunter, J. Org. Cliem., 36, 995 (1971).
m/e 117
'i
IrnT
I
127
I
l., . , .
,
,.,
,
50
50
. ,
,
,
,
,I. .!I 1m
150
,I,,
Im
150
m
,
1;
115
,
!, ,
,
,
,
,
,
M/E
DIETHYL FU"FFIATE. M = 172. ISOWlTAM C. I .
Figure 6. Isobutane CI mass spectra of diethyl maleate and diethyl fumarate measured at 280 "C Q M + ions t o behave much as one would expect protonated molecules to behave, based upon their solution chemistry (16-18) and further support for this notion, found in the spectra reported here, is of value insofar as it suggests that complicated and unprovable mechanisms are unlikely to be necessary t o a n understanding of the behavior of Q M + ions.
ACKNOWLEDGMENT We are indebted t o Seymour Meyerson for informing us of his results prior to publication and for his helpful comments. RECErVED
for review April 29,1971.
Accepted July 13,1971.
. . . _ _ ~ - .~. (16) H . M. Fales, H. A. Lloyd, and G . W . A . Milne, J . Amcv. Clwm. Soc., 92, 1590 (1970). (17) H. ZitTer, H. M. Fales, G. W. A. Milne, and F. H. Field, ihid., p 1597. (18) G. W . A. Milne, T. Axenrod, and H. M. Fales, ibid.,p 1570. ~~~~~
~
~~~~
~~
ANALYTICAL CHEMISTRY, VOL. 43, NO. 13, NOVEMBER 1971
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