S tereochemical Applications of Mass Spectrometry %Energy Dependence of the Fragmentation of Stereoisomeric Methylcyclohexanols

Alex G. Harrison and Margaret S. Lin Department of Chemistry, University of Toronto, Toronto, Ontario MSS 1A1, Canada

Breakdown graphs have been constructed from charge exchange data for the ephneric 2-methyl-, 3-methyl- and 4-methyl-cyclohexanols. Although the breakdown graphs for ephneric pah are essentialIy identical above -12eV recombination energy, significant Merenca are observed for the epimeric 2-methyl- and 4-methyl-cyclohexanols at low internal energies. For the 2-methylcydohexanols the ratio (W-H,O]'? M")J([M-H+O]"/M+'),, is 3.2 in the [c.&]+' charge exchange mass spectra. This is attributed to both energetic and conformational effects which favour the stereospecific cis-1,4-H2O elimination for the cis epimer. Tbe breakdown graph for trans-4-methylcyclohexanol shows a sharp peak in the abundance of the [M-H,O]" ion at -lOeV recombination energy which is absent from the breakdown graph for the cis epimer. This peak is attriiuted to the stereospecific cis-1,4-elimination of water from the molecular ion of the trans isomer; the reaction appears to have a low critical energy but a very unfavourable frequency factor, and alternative modes of water loss common to both epimers are observed at higher energies. As a result, in the [GF61+' charge exchange mass spectra the (F1-H,01"/F11+9~/~F1-H201"/F11+'), ratio is -24, compared to the value of 13 observed in the 70 eV El mas spectra. No dillere- are observed in either the metastable ion abrmdances or the associated kinetic energy releases for epimeric molecules.

INTRODUC'HON

Studies of substituted cyclohexanols have played a large role in developing our understanding of stereochemical effects on electron impact mass spectra.' A large part of these studies have been concerned with the elimination of water from deuterium-labelled cyclohexanols*~7 and from alkyl- substituted cyclohexanols, particularily those substi- tuted in the 4-p0sition.~-'' In summary, these studies have shown that water is eliminated from the molecu- lar ions of cyclohexanols in part by a stereospecific cis- 1,4-elimination through a boat-like conformation of the ring and, in part, by a non-stereospecific 1,3- elimination which appears to be preceded by carbon- carbon bond cleavage. In addition, for some molecules at least, some H 2 0 elimination also occurs involving the oxygen atom and two hydrogens from C(3) and C(5) of the ring. The net result is that an alkyl substituent in the 4-position of cyclohexanol strongly influences the extent of water loss from the molecular ion depending on its stereochemistry, while alkyl groups in the 2- or 3-position have little or no effect.

A number of w o r k e r ~ ' " , ~ . ~ ~ - ~ ~ have emphasized the advantage of using low ionizing energies and low source temperatures in the study of stereochemical effects on mass spectra. The present study of the methylcyclohexanols uses charge exchange mass spec- trometry, not only to explore the low energy stereo- specific fragmentation reactions but also to explore in a more general wav the energy evolution of the frag-

mentation of the methylcyclohexanol molecular ions. The electron impact mass spectra of mixtures of epim- ers were reported initially by Friedel et all4 In the light of these data, Budzikiewicz et ~ 1 . ' ~ have proposed mechanisms to rationalize the formation of some of the major fragment ions. Some support for these mechanisms has been derived from limited isotopic labelling

EXPERIMENTAL

The charge exchange mass spectra were obtained by chemical ionization methods using a DuPont 21-490 mass spectrometer as described previously. 17,18 Source temperatures were -100 "C with the samples being introduced through a heated inlet system at - 100 "C. The charge exchange reagent ions used were (recom- bination energy in eV in brackets) [C6F6]+' (10.0), [CS,]" (10.2), [COS]" (11.2), Xe" (12.51, [N20]+' (12.9), [CO]" (14.0) and [NJ' (15.3). The methods of production of these reagent ions have been de- scribed p rev iou~ ly '~* '~ with the exception of [C,F,]+' and [N,O]+'. The former ion was the dominant one (>95% total ionization) observed in a 10% C6F6-90O/! C 0 2 mixture at -0.2 Torr source pressure; the recom- bination energy was taken as being equal to the ioni- zation energy of hexafluorobenzene (10.0 eV19). The [N,O]+' reagent ions were prepared by ionization of a 10% N,0-90'/0 N2 mixture at -0.2Torr ion source pressure; the recombination energy of [N,O]" is re- ported" to be 12.9eV.

0 Wile! Heyden Ltd. 1984

CCC-0030-J93X8~'00 19-0067%02.50

ORGANIC MASS SPECTROMETRY, VOL. 19, NO. 2, 1984 67

A. G. HARRISON AND M. S. LIN

Electron impact (70 eV) mass spectra were obtained using an AEI MS-902 mass spectrometer at source and inlet temperatures of -100°C. Metastable ion abundances for fragmentation of molecular ions in the first drift region of the MS-902 were recorded by the accelerating voltage scan technique21 with all metasta- ble ion signals being recorded at 7.5 kV. Kinetic energy releases were evaluated from the metastable peak widths at half-height after correction for the main beam width.

The stereoisomeric methylcyclohexanols were ob- tained from K and K Laboratories.

RESULTS AND DISCUSSION

2-Methylcyclohexands

The charge exchange data for the cis- and trans-2- methylcyclohexanols are summarized in the form of breakdown graphs in Fig. 1, while the 70eV mass spectra are included in Table 1. Figure 1 shows only the major ions observed; at higher recombination energies a wide variety of ions were observed at low intensities consistent with the complexity of the EI mass spectra. The dominant low energy fragmentation routes of the molecular ions involve elimination of H20 to form [C,Hl2]" and elimination of OH' to form [C,H,,]+; the latter route is much more preval- ent than would be predicted from the EI mass spectra. The reasons for this difference are not known. The [M-H,O]+' ion fragments to form m/z 81 ([C,H,]') by loss of CH3 and, possibly, by loss of GH4 to form m/z 68 ([C5H8]+.). Interestingly, the latter fragment ion is much more prominent for the 2-isomers than for

I .o trans-2-Methylcyclohexonol

1

cis -2-Methylcyclohexono1 7 i

I I 0 1.1 12 I: 1 ' 4 I: Ik

Recombination energy (eV)

Figure 1. Breakdown graphs for 2-methylcyclohexanols.

Table 1. 70 eV electroa impact mass spectra of methyl- cyclohegands

m/z

114 113 99 97 96 95 86 85 81 72 71 70 69 68 67 58 57 56 55 54 53 44 43 42 41 40 39

cis-2-Me

18.3 1.3 1.3 2.6

63.4 5.7 7.2 7.8

60.8 7.8

50.3 13.7 5.2

71.9 21.6 15.0 100 7.2

39.2 17.0 7.8

26.8 22.9 19.6 37.9 3.3

19.6

trens-2-Me

23.0 1.3 1.3 1.3

60.5 5.3 7.8 7.9

58.6 7.9

51.3 17.1 4.6

73.0 20.4 15.1

7.2 38.2 17.1 6.6

24.3 22.4 19.1 36.2 2.6

17.1

100

cis-SMe

1.3 1.7 1.3 0.9

67.4 6.2 1.3 0.9

44.0 - 100 8.8 6.1

11.5 10.1 4.0

37.4 17.2 25.1 7.5 4.9

18.1 16.3 15.0 23.8 1.7

11.5

tnns-3-Me

2.2 1.6 2.7 1.6

74.1 6.0 2.1 1.1

62.7

100 11.9 7.0

15.1 12.4 4.9

44.9 8.1

38.4 10.3 8.7

23.2 24.9 18.9 37.8 3.2

20.0

-

ds4Me

17.7 4.2

1 .o 31.6 5.1 3.4 5.0

31.2

13.9 38.8 2.5 8.4 7.6

48.5

11.0 25.7 4.6 4.6

10.5 8.4 7.2

25.3 1.7 9.3

-

-

1 s

QMS~MS

1.8 1 .o

1 .o 41.7

5.5 3.0 3.0

49.2

10.0 27.1 3.5

12.1 12.6 45.7

13.0 37.2 6.5 9.0

21.6 15.1 12.6 49.7 3.5

23.1

-

-

100

the 3- or 4-isomers. This is apparent both from the breakdown graphs (Figs 1-3) and from the 70 eV mass spectra (Table 1).

The major alternative and higher energy fragmenta- tion routes of the molecular ions involve formation of m/z 71 ([C4H,0]') and formation of m/z 57 ([C3H50]+). The reactions forming these product^'^ are outlined in Scheme 1; it is obvious both from the breakdown graphs and from the 70eV mass spectra that formation of [C3H50]+, involving initial rupture of the more highly substituted bond, is the more favourable reaction.

The breakdown graphs for the two epimers are practically identical above 11-12 eV recombination energy. However, at the lowest recombination ener- gies there are significant differences in the relative

1 I I I I I I I .o cis-3- Methylcyclohexml

- 0

g 0.4 2 LL

0.2

0

Recombination enerqy (eV)

Figure 2. Breakdown graph for cis-3methylcyclohexanol.

68 ORGANIC MASS SPECTROMETRY, VOL. 19, NO. 2, 1984

STEREOCHEMICAL APPLICATIONS OF MASS SPECTROMETRY

I .o

0.6

0.61 1 a4

a2

0 I0 1.1 I2 I 3 I4 I 5 I6

Recombination energy (eV)

Figure 3. Breakdown graphs for 4-rnethylcyclohexanols.

intensities of MI'. and [M- H20fC' ([C,H,,]'). Thus in the [C6F6]" charge exchange mass spectra the [M- H201+'/[M'J+' ratio is 1.4 for the cis epimer but only 0.44 for the trans epimer while in the [C!$l+ charge exchange mass spectra the same ratio is 1.4 for the cis epimer and 0.64 for the trans epimer. The origins of these differences in the low energy charge exchange mass spectra appear to be two-fold. The heat of formation of the cis epimer (AH: = -327.2 kJ mol-l) is higher than that of the trans epimer (AH:= -352.7 kJ mo1-1);22 thus assuming identical structures and heats of formation for the [M - H203+' fragments, the critical energy for formation of this fragment should be 25.5 kJ mol-I lower for the cis epimer. In addition, the boat conformation for the cis epimer, placing a 4-H and the OH group in close proximity is favourable because the CH3 group is in an equatorial position. By contrast, such a conformation is less favoured for the trans epimer since it places the CH3 group in a sterically more crowded position. Thus both enthalpic and conformational effects favour loss of H 2 0 from the cis epimer.

These differences are observed chiefly in the low internal energy region and the ratio ([M - H,O]+'l [Ml+'),is/([M - H201+/[M]+'),, decreases from 3.2 in

m/z 71

Scheme 1

the [C6F6]+' charge exchange spectra to 2.2 in the [CS,]" charge exchange spectra and to 1.4 in the [COS]" charge exchange mass spectra. The 70eV electron impact mass spectra (Table 1) give a value of 1.3 for the same ratio. The EI mass spectra sum the breakdown graphs over an internal energy distribution extending to -10 eV internal energy (19-20 eV re- combination energy) and thus it is not surprising that the differences observed are decreased in magnitude in the 70 eV mass spectra. Akhtar et al." have reported that the two epimers give almost identical mass spectra when ionized by 10.19 or 21.22eV photons. The latter result is not surprising since with 21.33 eV photons ionization will give a wide distribution of internal energies; however, in light of our charge exchange results it is surprising that differences were not observed in the spectra obtained with 10.19eV photons.

3-Methylcydohexanols

The 70 eV EI mass spectra of the epimeric 3-methyl- cyclohexanols (Table 1) are very similar. The break- down graphs obtained from the charge exchange mass spectra also are essentially identical, that for the cis epimer is shown in Fig. 2. (As in Fig. 1 only the major fragment ions are shown; numerous low intensity frag- ment ions were observed at higher recombination energies). Again the major primary fragmentation in- volves elimination of H 2 0 to form [C7HI2]+', which subsequently fragments further by loss of CH3' to form [C6H,]+ (mlz 81). The alternative fragmentation reactions involving fission of the carbon ring (Scheme 2) result in formation of mlz 71 ([C,H,O]') and m/z 57 ([C,H,O]'), with the former being much more prominent.

Given the rather substantial differences in the low energy charge exchange mass spectra of the epimeric 2-methylcyclohexanols it is at first sight surprising that similar differences are not observed for the 3-methyl- cyclohexanols. However, in this case the enthalpic and conformational effects act against each other and can- cel out. As for the 2-methylcyclohexanols a boat con- formation with a 4-H and the OH group in close proximity is favoured for the cis epimer but is un- favourable for the trans epimer. However, in contrast to the 2-methyl compounds the heat of formation of the cis epimer (AH: = -351.0 kJ mol-') is lower than that of the trans epimer (AH: = -329.3 kJ moI-'):2 making the critical energy for fragmentation of the cis epimer higher than that of the trans epimer (assuming identical structures for the [M-H20]+' fragment). A

Scheme 2

ORGANIC MASS SPECTROMETRY, VOL. 19, NO. 2, 1984 69

A. G. HARRISON AND M. S. LIN

further difference between the 3-methylcyclohexanols and the 2-methylcyclohexanols is the much lower in- tensities for the [MJ" ions for the former in both the low energy charge exchange mass spectra and in the EI mass spectra.

4-Methylcy clohexanols

The 70 eV EI mass spectra of the epimeric 4-methyl- cyclohexanols are recorded in Table 1. The ([M- H,O]+'/[M]+'),,/([M - HzO]+'/[M]+'),,, ratio observed is 13.3 in good agreement with the value of 13 re- ported by Green et al.'" From the photoionization spectra reported by Akhtar et al." one derives ratios of -9 for ionization with 21.22 eV photons and - 10 for ionization by 10.19 eV photons. The greater water loss for the trans epimer is attributed to the stereo- specific cis-1,4-Hz0 elimination reaction from the in- tact cyclic molecule, a reaction which is not possible for the cis epimer. It might be noted that the heats of formation of the neutral molecules," cis = -347.7 kJ mol-', trans = -367.4 kJ mol-', would indicate that enthalpic effects would favour HzO elimination from the cis epimer.

The breakdown graphs derived for the two epimers from the charge exchange data are presented in Fig. 3 (only the major fragment ions are shown). Beyond -12 eV recombination energy the two breakdown graphs are essentially identical showing m/z 57 ([C,H,O]') as the major fragment ion. This ion arises by ring cleavage reactions similar to those depicted in Schemes 1 and 2. Substantial differences are observed in the breakdown graphs at low recombination ener- gies in terms of the relative abundances of the [MI"' and [M - HzO]+' ([C,Hlz]+*) intensities. The trans epimer shows a pronounced peak in the [C,Hl,I+ ion intensity at - 10 eV recombination energy, which is not seen for the cis epimer. This sharp peak for the

m c

P n

2

O m + 0 - B "L!,,, J,[ , 1 ~ ilei , ,. , H ' . g

40

40 60 00 100 I20

-Hp [M]"

0

m/z Figure 4. [C6Fel+' charge exchange and 70 eV El mass spectra of 4-methylcyclohexanols.

trans epimer presumably reflects the occurrence of the stereospecific cis-1,4-water elimination reaction which has a favourable critical reaction energy but an un- favourable frequency factor, because of the highly structured transition state, and, thus, with increasing internal energy rapidly loses out to the alternative water elimination reaction involving (for both epimers) ring cleavage and 1,3-H20 elimination, a reaction with a more favourable frequency factor.

Because of the sharp maximum in the breakdown graph for the trans epimer, charge exchange mass spectra at this energy will show much more pro- nounced differences than electron impact or photon impact mass spectra, which sum over the breakdown graph and include large portions which are identical for the two epimers. This is illustrated dramatically by the comparison of the [C6F6]+' charge exchange mass spectra and the 70 eV EI mass spectra shown in Fig. 4. Not only are the charge exchange mass spectra much simpler but also they yield a ([M - H,O]+'/[M]+'),,/ ([M-H~Ol+'/[M]+')cis ratio of 23.5 compared to the ratio of 13.3 observed in the EI mass spectra.

Metastable fragmentation of methylcydohexand molecular ions

In the light of the rather large differences observed in the low energy charge exchange mass spectra, particu- larly for the 4-methyl epimers, we have studied the metastable ion fragmentation reactions of the epimeric molecular ions to determine whether these differences are reflected either in metastable ion abundances or in kinetic energy releases. Table 2 records the metastable ion intensities observed for fragmentation of the molecular ions of the six methylcyclohexanols in the first drift region of the MS-902 mass spectrometer. A multitude of fragmentation reactions are observed, many in low abundance, including in several cases the products of sequential two-step fragmentation reac- tions. However, in all cases the major metastable fragmentation reaction involves elimination of H,O, accounting for 6 6 8 5 % of the total metastable ion intensity. The metastable ion spectra of stereoisomers are identical, presumably because the majority of molecular ions reaching the drift region have lost their steric identity by a-cleavage of the ring; however, there are substantial differences among positional isomers. Thus, for example, the m*(96)/m*(70) ratio

Table 2. Metastable ions from fragmentation of methyl- cyrlohexand molecular ions

% Total ionization

Product Neutrai trans-2- trans& trans4 m/z fragment cis2-Me Me ci&Ma Me c i b o h b Me

99 CH, 0.011 0.010 0.031 0.015 0.003 0.005 96 H,O 0.85 0.84 0.64 0.68 0.70 0.64 86 CZH, 0.045 0.051 0.22 0.20 0.12 0.13 85 C,H, 0.026 0.033 0.007 0.007 0.057 0.057 81 H2O+CH, 0.002 0.002 0.010 0.014 0.016 0.020 72 GH6 0.007 0.009 0.002 0.003 - - 71 GH, 0.048 0.043 0.082 0.066 0.017 0.030 70 7 0.002 0.002 0.015 0.013 0.083 0.12

5 8 7 0.007 0.007 0.001 0.001 0.002 0.002 68 H,O+&H, 0.004 0.005 - - - -

70 ORGANIC MASS SPECTROMETRY, VOL. 19. NO. 2, 1984

STEREOCHEMICAL APPLICATIONS OF MASS SPECTROMETRY

Table 3. Kine& energy releases (Tm) for fragmentation of molecular ions

T,,Z(WV)

product miz cis-2-Me uans-2-Me cis4Me trans-8Me cis4Me trans4Me

96 17 17 20 20 22 22 86 12 12 13 12 86 110 85 15 15 16 11 11 13 71 11 12 11 11 11 11 70 12 12 12 12 13 12

is 400 *20 for the 2-methyl epimers, 45 f 5 for the 3-methyl epimers and 7*2 for the 4-methyl epimers. The observation of an abundant metastable ion for loss of H20 from the trans-4-methylcyclohexanol molecular ion is in contrast to the report by Akhtar er al.," that while such a metastable transition was ob- served for the cis epimer it was not observed for the trans epimer.

In a further attempt to distinguish between epimers the kinetic energy releases associated with the metast- able fragmentation reactions were measured with the results shown in Table 3. The results for all six com- pounds studied are very similar, the only significant difference being the noticeably higher kinetic energy releases associated with the loss of C2H4 from the 4- methylcyclohexanol molecular ions. In particular, the differences observed in the breakdown graphs for the epimeric 4-methylcyclohexanols are not reflected in either the relative metastable ion abundances or the kinetic energy releases for metastable fragmentation of the molecular ions.

Acknowledgement

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

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Received 7 March 1983; accepted 24 May 1983

ORGANIC MASS SPECTROMETRY, VOL. 19, NO. 2, 1984 71