Stereochemical applications of mass spectrometry. II—Chemical ionization mass spectra of isomeric dicarboxylic acids and derivatives

Stereochemical Applications of Mass Spectrometry 11-Chemical Ionization Mass Spectra of Isomeric Dicarboxylic Acids and Derivatives Alex. G. Harrison and R. Krisha Mohan Rao Kallury Department of Chemistry, University of Toronto, Toronto, Canada MSSlA1

The Hz and CH, chemical ionization mass spectra of the cis dicarboxylic acids, maleic and citraconic acid, show much more extensive loss of H,O from [MH]+ than the trans isomers, fumaric acid and mesaconic acid. Similarly, esters of maleic acid show a much more facile loss of ROH (R=alkyl or phenyl) from [MH]' than do esters of fumaric acid. Similar differences are observed in the chemical ionization mass spectra of the isomeric phthalic and isophthalic acids and derivatives, where the ortho isomers show more extensive fragmentation of [MH]+ than the rneta isomers. The facile fragmentation of [MH]' for the cis and ortho isomers is attributed to ROH elimination involving interaction between the two carboxylate functions and forming the stable cyclic anhydride structure for the fragment ion. By contrast ROH elimination from [MH]+ for the trans and metu isomers requires a symmetry-forbidden [1,3]-H migration in the carboxyl protonated species and cannot lead to the cyclic anhydride structure. The chemical ionization mass spectra of cis and trans cyclohexane-1,2-dicarboxylic acids are essentially identical and show extensive fragmentation of the [IMH]' ion. Experiments using deuterium labelling show extensive carboxyl group interactions for both isomers. The chemical ionization mass spectra of malean*c and phthalanilic acids and of the related anhydrides and imides also are reported, as are the electron impact mass spectra of diphenyl maleate, diphenyl fumarate, diphenyl phthalate, maleanilic acid and phthalanilic acid.

A significant development in organic mass spectrometry in the past decade has been its application to stereochemical problems involving both simple and complex molecules.' Of particular interest in the present context are the extensive investigations of the effect of geometrical isomerism on the electron impact (EI) mass spectra of olefinic and alicyclic dicarboxylic acids and derivatives. The mass spectrum of the cis dicarboxylic acid, maleic acid, is quite different from the mass spectrum of the trans compound, fumaric acid, showing not only different relative ion intensities but also different fragmentation routes.* Similar differences are observed in the EI mass spectra of their alkyl e~ters .3 ,~ The EI mass spectra of the isomeric cyclohexane-1,2-dicarboxylic acids and cyclobutane- 1,2-dicarboxylic acids similarly shows large differences in fragmentation routes and relative ion intensities. By contrast the geometrically isomeric cyclohexane- 1,2- dicarboxylic acids exhibit very similar mass spectra,6 although the mass spectra of the isomeric anhydrides differ markedly.'r8

In contrast to the considerable study of the effect of geometrical isomerism on the El mass spectra of dicarboxylic acids, there has been little study of these compounds by chemical ionization (CI), although the CI mass spectra of isomeric cyclic diols and derivatives have received extensive study.g One brief report" on the CI mass spectra of maleates and fumarates reported substantial differences. The present work re- ports a study of the CI mass spectra of a selection of dicarboxylic acids and esters to probe the effects of

geometrical isomerism on the CI induced fragmentation. The compounds examined are summarized below, and include the related anhydrides, imides and amido acids. The EI mass spectra of those compounds not reported previously are discussed briefly.

R'-C-CO,R H-C-CO2H

H-C-COZR

(5) 9 R = R ' = H (1) R = R ' = H R = C2H,; R' = H (2) R = C2H,; R' = H (6) R=C,H,; R1=H (3) R=Ph; R '=H (7) R = H ; R'=CH, (4) R = H ; R'=CH, (8)

CO2R

\ \ C02R CONHC,H, C02R

15 R = H (10) R = H (13) R=CH, (11) R=CH, (14) R = C,H5 (12)

0

x = O (16) X = O (18) 20 21 X = NH (17) X = NH (19)

0 Heyden & Son Ltd, 1980

CCC-0030-493X/80/0015-0277$03.50

ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 277

A. G. HARRISON AND R. K. M. R. KALLURY

Table 1. EI mass spectra of diphenyl maleate, diphenyl fumarate and diphenyl phthalate

Relative intensity (%)

Diphenyl Diphenyl Diphenyl Ion maleate furnarate phthalate

[MI'' 9.3 10.9 0.4 [M - C,H50]' 100 100 100 [M - C,H,O- CO]' 48 58 1.2 [M - C6H50 - CO - CO,]' 16 19 3.4

[C,H,OHl+' 9 10 - - [C,H$J+ 13

[c1&1' 32 22 8.2 -

EI mass spectra of diphenyl maleate (3), diphenyl fumarate (7) and diphenyl phthalate (12)

The 70eV mass spectra of diphenyl maleate and diphenyl fumarate are summarized in Table 1. The spectra are very similar, the major difference being the low intensity mlz 99 peak (protonated maleic anhydride) observed for 3, which is absent in the spectrum of 7 . This difference also is found4 for the methyl esters where mlz 99 is observed in low abundance in the spectrum of the maleate only. The major fragmentation route observed for both molecular ions is loss of the phenoxy radical to afford the base peak, from which CO and CO, are lost successively. Metastable peaks are observed for each step in this sequential fragmentation. Formation of the phenol molecular ion, which is more pronounced for the maleate ester, presumably involves migration of an olefinic hydrogen to the phenoxy group.

Diphenyl phthalate (12) shows (Table 1) only an extremely weak molecular ion (0.4'/0), the spectrum being dominated by the [M- OPh]+ ion, which, as in the maleate and fumarate fragments further by successive loss of CO and CO,. N o m / z 149 product (protonated phthalic anhydride) is observed, as is the case for alkyl phthalates," nor is a phenol ion observed as was found for the maleate and fumarate esters.

EI mass spectra of maleanilic acid (9) and phthalanilic acid (15)

Although these two compounds find extensive use in synthetic as well as analytical organic their mass spectra do not appear to have been re-

Table2. El Mass spectra of maleanilic and phthalanilic acids

Ion

[MI" [M-OH]' [M - H,Ol+' [ M - CO,HI+ [M-H,0-C02]" [M - NHC,H,I' [M - NH,C6H51" [M- NH2C6H5-C0,]+' [C&&.NH,I'-

Relative intensitv (%) Malaanilic acid Phthslanilic acid

33 11.5 0 0.9 3 8

11 0 0 6

14 20 0 20 0 70

100 100

ported. The 70eV mass spectra are summarized in Table 2.

The major fragmentation route for bbth acids involves formation of the aniline molecular ion, the base peak in both spectra. Both acids show H,O elimination from [MI"; for phthalanilic acid this fragmentation is followed by loss of CO,. In the phthalanilic acid system the molecular ion also shows elimination of neutral aniline to form, nominally, the phthalic anhydride molecular ion which further loses CO,. Interest- ingly, the maleanilic acid molecular ion does not fragment by this reaction channel. Presumably in the competitive reactions (1) and (2) the aromatic ring of

the phthalic acid system lowers the ionization energy of the anhydride sufficiently to make reaction (1) competitive with reaction (2), formation of the aniline molecular ion and neutral phthalic anhydride, while reaction (1) is not competitive with (2) in the maleanilic acid system. Although it has been that in such complementary fragmentation reactions the charge resides preferentially on the species of lower ionization energy, quantitative data are not present to test this for the present systems. Both acids show low intensity peaks corresponding to the protonated anhydride formed by loss of the anilino radical. In addition for maleanilic acid a low intensity peak is observed at m/z 146 corresponding to CO,H loss from the molecular ion; a similar fragmentation is observed for maleic and fumaric acids.'

CI mass spectra of dicarboxylic acids (195,4989 10,13)

The H2 and CH, CI mass spectra of the cis-rrans isomeric dicarboxylic acids, maleic-fumaric and citraconic-mesaconic, are shown in Figs. 1 and 2. The cis isomers, maleic acid and citraconic acid, show only low intensity [MH]+ ion signals, the base peaks in both the H, and CH, CI mass spectra corresponding to [MH-H,O]+. By contrast the [MH]' ions are much more pronounced in the CI mass spectra of the trans isomers, fumaric acid and mesaconic acid, with [MH]+ constituting the base peak in the CH, CI mass spectra. In addition for the trans isomers the [MH-H,O]+ fragment shows a lower stability in the more exothermic protonation by [HJ and fragments further by loss of CO to a greater extent than is observed for the cis isomers. A minor fragment route involves loss of CO, from [MH]', a fragmentation mode which is more prominent in the CH, CI of the cis acids than the

278 ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 @ Heyden 6i Son Ltd, 1980

STEREOCHEMICAL APPLICATIONS

40

I

OF MASS SPECTROMETRY-I1

-

[MH]'- I

FiH-'OOH H,CI CH-COOH

[MH-HzO]'

1 j

0' I I I I ' I 1 I

I I I ' 40 50 60 70 80 90 100 I10 120

m /z

Figure 1. CI mass spectra of maleic and fumaric acids.

trans acids. In addition, the H,CI mass spectrum of furnaric acid only shows a low intensity peak corresponding to loss of CO from [MH]+. The EI mass spectrum of this acid also shows a peak corresponding to loss of CO from the molecular ion.

The cis dicarboxylic acids are known to readily dehydrate thermally to form the respective anhydride.' If this were to occur in the present case protonation of the anhydride would lead to the observed base peak. Three pieces of evidence indicate that thermal decomposition is not important under our experirnen- tal conditions. First, the EI mass spectrum of maleic

8 0 t

[MHl'

H COOH [MH - H20]+

50 60 70 80 90 100 110 120 130 0 , I I I I I I I I I

50 60 70 80 90 100 110 120 130 m /z

Figure 2. CI mass spectra of citraconic and mesaconic acids.

@ Heyden & Son Ltd. 1980

acid measured under the same conditions was very similar to that reported by Bemit et aL2 Second, the iso-C,H,, CI mass spectra of the cis diacids showed predominantly [MH]+ and, third, the fragment ions observed in the H, CI of rnaleic anhydride (see below) were not observed in the H, CI of maleic acid. Thus we conclude that the large [MH-H,O]' peaks observed in the CI of the cis diacids result from fragmentation of the protonated acid and not from protonation of the anhydride produced thermally in the ion source.

A similar difference in the ease with which water is lost from the [MH]' ion is observed in the H, and CH, CI mass spectra of the isomeric phthalic and isophthalic acids (Fig. 3 ) . For the ortho isomer, phthalic acid, the [MH- H20]+ ion constitutes the base peak in both the H2 and CH, CI, with the [MH]+ ion signal being of low intensity. By contrast, for the metu isomer, isophthalic acid, the [MH]' ion intensity is much greater and, in fact, constitutes the base peak in the CH, CI mass spectrum. Loss of CO, from [MH]' is observed in all the CI mass spectra and for the H2 CI system sequential loss of two molecules of CO, leading to m / z 79 ([C,H,]') is a significant reaction, particularly for isophthalic acid. Loss of CO, from [MH]+ has been reported15 in the CI of spectra of benzoic acid and substituted benzoic acids. Thermal decarboxylation appears unimportant in these systems as no increase in the importance of these routes with increasing temperature was noted.

In contrast to the results observed for the cis-trans olefinic dicarboxylic acids (Figs. 1 and 2) the CI mass spectra in Fig. 4 of the isomeric cyclohexane-cis- 1,2-dicarboxylic acid and cyclohexane-trans-l,2-dicarboxylic acid show only slight differences in both the H2 and CH, CI mass spectra. For both isomers the fragmentation of the protonated molecule proceeds by sequential and alternating loss of H 2 0 and CO leading, in the case of the strongly exothermic protonation

[MH-HpO]' I $

80

40

I [MH -Hfl]+ t rMH-Ch1'

L -A

O H ) I I

I I I I I 1 70 80 100 110 120 130 140 150 160

m /I

Figure 3. CI mass spectra of phthalic and isophthalic acids.

ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 279

A. G. HARRISON AND R. K. M. R. KALLURY

8o

I

- "'- I

HE-COOPh [MH-PhOH]' [MH]' - - PhOOC-CH

h - 4 rn /z

0 80 90 100 110 120 130 140 150 160 170 180

Figure 4. CI mass spectra of cis and trans cyclohexane-l-2- dicarboxylic acids.

by [H3]+, to [C,H,]+ (m/z 81) as the base peak. The extent of fragmentation is considerably less for the less exothermic protonation in the CH, CI. It is clear that in this system the cis-trans isomerism has much larger effects on the EI mass spectra5 than on the CI mass spectra.

CI mass spectra of dicarboxylic acid esters

The enhanced fragmentation observed for the cis olefinic dicarboxylic acids and the ortho dicarboxylic acids also is observed in the CI mass spectra of the related esters. Figure 5 shows the H, and CH, CI mass

m/z

Figure 5. CI mass spectra of ethyl maleate and ethyl fumarate.

spectra of ethyl maleate and ethyl fumarate. In the H2 CI the major fragmentation reaction of the [MH]' ion involves C,H50H elimination and this reaction is much more pronounced for the maleate than the fumarate ester. The [MH- C,H,OH]+ ion fragments further by elimination of C2H4 (to give mlz 99), and this fragmentation is more pronounced for the maleate than the fumarate. A minor fragmentation route in the H, CI of both geometrical isomers involves C2H4 elimination from [MH]+. In the CH, CI mass spectra the dominant fragmentation of the protonated maleate ester is loss of C2H50H with loss of C2H4 being much less important. By contrast, for the protonated fumarate ester the extent of fragmentation is much less and the preferred fragmentation route is the successive loss of C2H4. This distinction between ethyl fumarate and ethyl maleate has been observed previously" in the lower energy isobutane CI mass spectra although the differences in the spectra are much more pronounced in the CH, CI mass spectra.

The H, and CH, CI mass spectra of diphenyl maleate and diphenyl fumarate are shown in Fig. 6 . The major fragmentation mode of [MH]+ involves elimination of neutral phenol and this fragmentation reaction is much more facile for the maleate than the fumarate, the difference being particularly noticeable in the CH, CI spectra. The protonated phenol ion, m / z 95, is observed in all spectra and, presumably, must involve migration of one of the olefinic hydrogens to the phenoxy group prior to fragmentation.

Figure 7 compares the H, and CH, CI mass spectra of dimethyl phthalate and dimethyl isophthalate. Again the major fragmentation route is elimination of ROH (R = CH,) from [MH]+ and this fragmentation is much more pronounced for the phthalate than the isophthalate. Loss of CO, from [MH]' also is observed, as has been reported13 previously for methyl

80

40

80

L- HE-COOPb I 1

[MH-PhOH-CO]'

HC-COOPh

PhOOC-!H ILMH- phOHJ' 1 [MH-PhOH-CO]'

HC-COOPh HC-COOPh

CHJI

[MH-PhOH]'

4 0 L L L J 0 90 100 110 130 140 150 170 180 260 270

rn/z

Figure 6. CI mass spectra of phenyl maleate and phenyl fumarate.

280 ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 @ Heyden & Son Ltd, 1980

STEREOCHEMICAL APPLICATIONS OF MASS SPECTROMETRY -11

801 acoocH3 OOCH,

100 iio 130 140 150 160 i io 160 150 m /z

Figure 7. CI mass spectra of methyl phthalate and methyl isophthalate.

benzoate. The enhanced fragmentation of the phthalate ester compared with the isophthalate ester is in contrast to the reported" isobutane CI mass spectra of the di-2-ethylhexyl esters where the isophthalate (and terephthalate) ester showed a greater extent of fragmentation than the phthalate ester.

The results for the acids and esters with a cis-trans configuration about a double bond and for the ortho- meta dicarboxylic acids and esters are in agreement in showing that the cis isomers and the ortho isomers exhibit a much more facile loss of ROH (R = H, alkyl, or phenyl) from the protonated molecule. It has been shown16 that the most stable form for protonated carboxylic acids and esters is the carbonyl protonated species. Recent in this laboratory has shown that HzO elimination from carbonyl protonated acids proceeds with an activation energy greater than the reaction endothermicity consistent with a symmetry- forbidden [ 1,3]-H migration prior to H,O elimination. The same situation undoubtedly applies for the protonated trans acids and esters and the meta acids and esters studied in the present work. However, for both the cis dicarboxylic acid derivatives elimination of ROH can proceed readily without a symmetry- forbidden H migration as outlined in Scheme 1 and, indeed, is related to the well known ortho effect' in E I mass spectra." In addition, as indicated in Scheme 1, the elimination also is aided by the formation of the appropriate protonated or alkylated anhydride. Obvi- ously this intramolecular catalysis of ROH elimination

0 II

0 II {p>EH -

I 1 'OR

1: OR'

Scheme 1

coupled with the stability of the product ion more than offsets the additional stabilization of the [MH]+ ion by internal solvation. By contrast, neither the trans nor the meta isomers have the stereochemistry permitting this intramolecular catalysis of ROH elimination nor the possibility of forming the cyclic anhydride derivative. This is obvious for the isophthalic acid system. The results €or the trans dicarboxylic acid systems show that the extent of trans + cis isomerization following chemical ionization must be very small.

In support of this interpretation we note that in the CD, CI mass spectrum of maleic acid [MD- H,O]+/[MD - HDO]' = 1.7, while in the CD, CI mass spectrum of fumaric acid [MD - H,O]+/[MD - HDO]+- 0.3. These results indicate that the added proton is largely lost with the neutral water for the trans acid but exchanges, or becomes equivalent, with the carboxylic hydrogens for the cis acid. The CD, CI mass spectra of both maleic acid-d, and fumaric acid- d, showed loss of D 2 0 only indicating no involvement of the olefinic hydrogens in the water elimination.

In contrast to the cis-trans olefinic dicarboxylic acids and derivatives, there are no significant differences observed in the H, or CH, CI mass spectra of the cis- and trans-cyclohexane- 1,2-dicarboxylic acids. Further, the isobutane CI mass spectra of the two isomers also were identical, showing predominantly [MH]' (50%) and [MH-H,O]+ (100%). These results are in contrast to the EI mass spectra where significant differences were observed5 and were attributed to a greater interaction of the carboxyl group with the ring hydrogen atoms in the cis(a, e) conformation compared with the trans (e, e ) conformation, where carboxyl group interactions were more prominent. Extensive carboxyl group interactions are indicated in the CI system by the observations that for both isomers the CD, CI mass spectra showed approx- imately equal [MD - H,O]+ and (MD - HDO]+ ion intensities, while in the CD, CI mass spectra of the cyclohexane dicarboxylic-d, acids only loss of D,O from [MD]+ was observed, indicating no involvement of the ring hydrogens for either isomer. In addition, the latter study also showed significant ion signals corresponding to [M+ C,D, - D,O]+ and [M+ C,D, - D,O]+ as well as [M + CzD5 - D,O - CO]', all indicative of carboxyl group interactions. The extent of interaction obviously does not depend on the conformation.

CI mass spectra of maleanilic and phthalanilic acid

Maleanilic acid (9) and phthalanilic acid (15) with their carboxyanilide and carboxylic acid groups offer the opportunity to compare the ease of loss of aniline with ease of loss of water from the protonated molecule. For the simple fragmentation process

RX - H+ + R' + HX ( 3 )

thermochemical arguments have been presented" that the ease of loss of HX should vary inversely with the proton affinity of HX and this has been confirmed experimentally for a number of simple

@Heyden & Son Ltd, 1980 ORGANlC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 281

A. G . HARRISON AND R. K. M. R. KALLURY

40

Table 3. CI mass spectra of maleanilic and phthalanilic acids relative intensities (%)

- CH4CI -

- [MH -OH]+' -

Relative intensities (%\ Maleanilic acid Phthalanilic acid

H2 CI CHI CI H2 CI CHI CI

- - 21 86 12 6 85 58 6 5 11 55 76 100 100 - - 5 - - - 8 - 100 100 58 75 32 10 27 9

2

- 10 - 22

- -

- - -

- 11 -

a0

40

although such a simple relation does not necessarily apply when [R]+ does not remain constant.

The H, and CH, CI mass spectra of maleanilic acid and phthalanilic acid are summarized in Table 3. The fragmentation following initial protonation proceeds by three pathways, loss of H,O, loss of aniline, and formation of protonated aniline as outlined in Scheme 2. For simplicity the protonated species is represented

- IW 121 131 I .

- [MH]* - - CGo

- CH4CI - - -

0 0

0 \

as the N-protonated species, although it is probable that the proton is mobile and transfers among the available sites. In the CH, CI mass spectra both

ment ions are observed which can be most readily accounted for by ethyl ion interaction with a carbonyl oxygen and the amide nitrogen respectively. Loss of H20 is more important for maleanilic acid than for phthalanilic acid, presumably reflecting the greater stability of the protonated N-phenyl maleimide compared with the maleic anhydride or protonated maleic anhydride formed in the other two fragmentation channels. By contrast protonated phthalanilic acid fragments mainly by loss of aniline or formation of protonated aniline reflecting the greater stability of the phthalic anhydride and protonated phthalic anhydride products. It is evident that the relative ease of loss of aniline and water is not related to their relative proton affinities but is strongly influenced by the relative

[M+ C2H5 - C6H5NH2]* and [C6H5NH2C2H,] frag-

I S 40

._ - 1

[MH -OHIT. L.." I -,, [MH-COOHI' I I I 1

8ol-

stability of the product ions formed, a not surprising conclusion.

CI mass spectra of anhydrides and imides

In the course of this study we also have obtained the H, and CH, CI mass spectra of maleic anhydride, maleiminde, phthalic anhydride and phthaliminde. The spectra are shown in Figs. 8 and 9. With the exception of the H, CI spectra of the two imides

282 ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 @ Heyden & Son Ltd, 1980

STEREOCHEMICAL APPLICATIONS OF MASS SPECTROMETRY -11

[MH]+ constitutes the base peak and the extent of fragmentation is small. For the two imides the base peak in the H2 CI corresponds to loss of H20 from CMH]+ presumably forming the stable cyano derivative of the appropriate acylium ion (Scheme 3).

through the heated inlet system. For the CI studies H2 and CH, pressures of a 0.3-0.5 Torr were employed.

Diphenyl fumarate (7) was prepared by refluxing molar proportions of fumaric acid and phenol (1 : 2) with excess (5 mol) of phosphorous oxychloride for 30 min on a steam bath followed by decomposition by ice and recrystallization of the crude ester (yield al- most theoretical) from ethanol, m.p. 162 "C. Diphenyl maleate (3) (rn.p. 72°C) was obtained by the same procedure starting from maleic acid, with the exception that the reaction was carried out at room temperature by allowing the mixture to stand for several hours. Maleanilic acid (9)'l and phthalanilic acid (13)'* were prepared by standard procedures. The remaining compounds were commercially available.

EXPERIMENTAL

The EI and CI mass spectra were obtained using a Dupont 2 1-490 mass spectrometer with source ternp- eratures of 100-150 "c- Solids were introduced by a direct insertion probe while liquids were introduced

Acknowledgement

The authors are indebted to the Natural Sciences and Engineering Research Council (Canada) for financial support.

REFERENCES

1. (a). S. Meyerson and A. W. Weitkamp, Org. Mass Spectrom. 1, 659 (1968); 2, 603 (1969); (b) M. Green, in Topics in Stereochernistry' Vol. 9, ed. by N. Allinger and E. L. Eliel, pp. 35-110. Wiley-lnterscience, New York (1976); (c) A. Mandelbaum, in Stereochemistry Fundamentafs and Spectrom. 5, 1313 (1977). Methods, Vol. 4, ed. by H. Kagon, p. 137, Georg Thieme Verlag, Stuttgart (1977); (d) M. Green, Pure Appl. Chem. 50, 185 (1978).

2. F. Benoit, J. L. Holmes and N. S. Isaacs, Org. Mass Spec- trom. 2, 591 (1969).

3. F. W. McLafferty, in Mass Spectrometry of Organic Ions, ed. by F. W. McLafferty, Academic Press, New York (1963).

4. J. H. Bowie, D. H. Williams, P. Madsen, G. Schroll and S. 0. Lawesson, Tetrahedron, 23, 205 (1967).

5. F. Benoit and J. L. Holmes, Org. Mass Spectrom. 6, 541 (1972).

6. F. Benoit and J. L. Holmes, Org. Mass Spectrom. 6, 549 (1972).

7. A. Karpati and A. Mandelbaum, Org. Mass Spectrom. 5, 1345 (1971).

8. H. Remane, H. Werner and R. Fehre, Tetrahedron, 31, 2972 (1975).

9. L. Dhaenens, C. C. Van de Sande and F. Vangaever, Org. Mass Spectrom. 14, 145 (1979) and references cited 22. J. Reid, J. Am. Chem. SOC. 39, 1249 (1917). therein.

10. H. M. Fales, G. W. A. Milne and R. S. Nicholson, Anal. Chem. 43, 1785 (1971).

11. H. Budzikiewicz, C. Djerassi and D. H. Williams, Mass Spectrometry of Organic Compounds, Holden-Day, San Francisco (1967).

12. G. Wilgetag and A. Martini, Weygand-Preparative Organic

13. C. I<. Sawers, J. Org. Chem. 34, 2275 (1969). 14. A. G. Harrison, C. D. Finney and J. A. Sherk, Org. Mass

15. H. lchikawa and A. G. Harrison, Org. Mass Spectrom. 13, 389 (1978).

16. (a) T. X. Carroll, S. R. Smith and T. D. Thomas, J. Am. Chem. SOC. 97, 659 (1975); (b) B. E. Mills, R. L. Martin and D. A. Shirley, J. Am. Chem. SOC. 98, 2380 (1976); (c) F. M. Benoit and A. G . Harrison, J. Am. Chem. SOC. 99, 3980 (1977).

17. N. E. Middlemiss and A. G. Harrison, Can. J. Chem. 57, 2827 (1979).

18. F. H. Field, in Mass Spectrometry, ed. by A. Macoll, p. 149. MTP International Review of Science, Physical Chemistry, Butterworths, London (1972).

19. I. Jardine and C. Fenselau, J. Am. Chem. SOC. 98, 5086 (1976).

20. A. G. Harrison and F. 1. Onuska, Org. Mass Spectrom. 13,35 ( 1 978).

21. H. E. Baumgarten (Ed), Organic Synthesis, Vol. 5, p. 944. J. Wiley, New York (1973).

Chemistry, p. 486. J. Wiley, London (1972).

Received 22 January @ Heyden & S 3n Ltd, 1980

accepted l4 March

0 Heyden & Son Ltd, 1980 ORGANIC MASS SPECTROMETRY, VOL. 15, NO. 6, 1980 283

Documents

Stereochemical applications of mass spectrometry. II—Chemical ionization mass spectra of isomeric dicarboxylic acids and derivatives