Fragmentation in Chemical Ionization Mass Spectrometry and the Proton Affinity of the Departing Neutral

Alex. G. Harrison?

Francis I. Onuska Department of Chemistry, University of Toronto, Toronto, Canada M5S 1Al

Environment Canada, Canada Centre for Inland Waters, Burlington, Canada L7R 4A6

Chemical ionization mass spectra of six 5,6-dihydro-2-methyl-1,4-oxathiins, and some of the sulfoxides and sulfones derived therefrom, have been determined employing hydrogen, methane and isobutane as reagent gases. The major fragmentation reaction of the protonated molecule, [R’COX.H]+, involves loss of the neutral HX molecule. For the sulfides and sulfones, with X ranging from OH to N(CH,)C,H,, it is observed that the importance of this fragmentation is inversely correlated with the proton affinity of the departing HX molecule in both the HZ and CH, chemical ionization. For the sulfoxides no consistent correlation is observed and this is attributed to the interference of competing and/or consecutive fragmentation reactions. In the isobutane chemical ionization mass spectra only the compounds studied.

protonated molecule is observed for most of the

INTRODUCTION

A common reaction in chemical ionization mass spec- trometry (c.i.m.s.) involves the loss of a functional group X, as the stable neutral molecule HX, from the protonated molecule [reaction (l)].

[RX.H]++ [R]++HX (1)

Filed’ has predicted that the extent to which reaction (1) occurs should be inversely proportional to the proton affinity of the neutral HX molecule eliminated. Although there have been few systematic studies of the extent of reaction (1) as a function of the group X, the general experience in c.i.m.s. tends to support this prediction in that it is observed that groups (such as OH,Br), where H X has a low proton affinity, are readily lost, while groups (such as NH,), where HX has a high proton affinity, are less readily lost. Some direct support for the prediction has come from the study by Jardine and Fenselau’ of the methane c.i. mass spectra of a number of cyclohexyl derivatives where the substituent was varied to give a wide range of proton affinities of the HX neutral. Although there was a general inverse trend of the extent of reaction (1) (as measured by the [R]+/[RX.H]+ ratio) with the proton affinity of HX, there were a number of anomal- ous results, some of which could possibly be attributed to competitive fragmentation reactions of [RX.H]+. Thus, Jardine and Fenselau’ suggested that the inverse correlation with proton affinity may only be valid where other fragmentation reactions are negligible,

t Author to whom inquiries should be directed.

@ Heyden & Son Ltd, 1978

where the departing X group is small, and where the initial site of protonation is located on X.

We recently have reported3 the CH, and H, c.i. mass spectra of 5,6-dihydro-2-methyl- 1,4-oxathiin-3- carboxanilide (la), and the sulfide (2a) and sulfone (34 derived therefrom. In all cases, the major frag- mentation reaction of the protonated molecule in- volved loss of neutral aniline (HX), although in the more exothermic H2 c.i. systems further fragmentation and/or alternative fragmentation was observed. In connection with other studies we had available a number of other derivatives lb-lg, 2b, 2c, 2f, 2g and 3b-3g, where the neutral HX formed in reaction (1)

l a . X = NHC,H, lb: X = OH 2b: X = O H le: X = OCH,C=CH Id: X=NH, l e . X = NHCH, If: X = NHC,H,CH,(p) lg: X = N(CH,)C,H,

2a: X=NHC,H,

2c: X = OCH,=CH 2f: X = NHC,H,CH,(p) 2g: X = N(CH,)C,H,

3a: X = NHC,H, 3b: X = O H 3c: X = OCH,=CH

3e: X=NHCH, 3f: X = NHC,H,CH,(p) 3g: X = N(CH,)C,H,

3d: X=NH,

O030-0493X/78/00 13-0035 $02.00

ORGANK MASS SPECTROMETRY, VOL. 13, NO. 1, 1978 35

A. G. HARRISON AND F. I. ONUSKA

exhibits a range of proton affinities. Therefore, it appeared that these series of compounds might pro- vide a useful test of Field's predictions, and, further, since the complexity of X changes greatly, the restric- tions proposed by Jardine and Fenselaw2 Accordingly, we have determined the H2, CH, and isobutane c.i. mass spectra of the three series of compounds. The use of the three reagent gases permits an evaluation of the effect of the exothermicity of the initial protona- tion reaction on the anticipated correlation, while examination of the relevant sulfides, sulfoxides and sulfones provides information on the effect of the oxidation state of the sulfur centre in the molecule on the extent of fra mentation and on the correlations. The earlier study indicated that, with a given reagent gas, the extent of fragmentation increased with oxida- tion state of the sulfur.

B

EXPERIMENTAL

Chemical ionization mass spectra were obtained using a Dupont 21-490 mass spectrometer equipped with a high pressure chemical ionization source. Reagent gas pressures were in the range 0.3-0.5 Torr. Samples were introduced into the source by the solids probe insert. The probe temperature (-100 "C) and source temperature (-- 140 "C) were dependent upon the minimum temperature necessary to volatilize the sam- ple while producing an adequate ion current, but were all within about a twenty degree range. The details of the preparation of the compounds will be presented elsewhere."

RESULTS AND DISCUSSION

Sulfides

The H, c.i. mass spectra of the sulfides la-lg are summarized in Table 1. As was observed previously3 the major fragmentation reaction involves loss of neutral HX from the protonated molecule [reaction (l)], the product ion comprising the base peak in all

Table 1. HZ c.i. mass spectra of sulfides (1)'

X [RX.HI' [Rl+ ' lRl+I[RX.HI+

OH 4.7 65.1 13.9

OCH2C=CH 12.3 47.8 3.9 NH2 6.4 44.1 6.9

NHCeH5 17.0 50.6 2.8,

NHCHl 16.4 35.6 2.1,

N(CHn)CsH6 20.1 44.4 2.2, NHCsH4CH3 24.6 33.1 1.35

PA(HX)'

169

-185 201

210

212

216 216

Other ions (abundance)d

[MI' (25.61, [M-HI' (3.4).

[MI' (32.8), [M-HI' (2.9) [M1'(10.3), [M-H1+(4.9), [MH-28](16.2), 117 (4.4) [MIt (18.5). [M-HI' (3.5) IMH-281C (2.6),117 (5.3) IM1'(26.4), [M-HI' (6.2) [MH-281' (4.7), 117 (3.2)

[MI? (20.0). 134 (14.2) [M1'(12.4), [M-HI' (8.7) IMH-281' (2.9). 117 (6.6)

117 (0.9)

Intensities as % of total additive ionization.

Proton affinities in kcal mol-', see text. For brevity M has been used to represent RX throughout the

bMle 143.

tables.

spectra. Relatively abundant molecular ions, [MI', formed by charge transfer from [H3]+, are observed as well as lower abundance [M-H]+ ions, presumably originating by hydride ion abstraction. Minor fragmen- tation pathways of the protonated molecule lead to [MH - 28]+, presumably involving loss of CZH4, [reac- tion (2)], and to m/e 117, which can be formulated as reaction (3).

0 6 cxcH3 .H+ + ( : y c H 3 . H + + O=+y-z

s c-Y-z O H I t I (3)

It is interesting to note that reaction (3) is not observed for l g which contains no transferable H on the nitrogen adjacent to the carbonyl function, but rather a significant ion current is observed at m/e 134 presumably corresponding to the [C,H,N(CH,)CO]' fragment ion.

Column 4 of Table 1 lists the observed [R]+/[RX.H]+ ratios, indicative of the extent to which reaction (1) occurs, and compares this ratio with the proton affinity of the neutral HX molecule listed in column 5 . The proton affinities of H20 and NH3 are taken from the recent work of Yamdagni and Kebarle,' while for the other amines the values re- ported earlier by Yamdagni and Kebarle6 have been recalculated to PA(NH3) = 201 kcal mol-'. The proton affinity of propargyl alcohol has been assumed to be similar to the proton affinities of the corresponding C3-C4 saturated alcohol^.^ There is quite a satisfac- tory inverse correlation of the [R]+/[RX.H]+ ratio with the proton affinity of the HX neutral, although compound l c appears out of line for unknown reasons.

In the CH, c.i. mass spectra of the sulfides (Table 2) the [RX*H]+ and [R]+ ions dominate the spectra. The extent of reaction (1) decreases dramatically with the proton affinity of HX, with the result that [R]+ ac- counts for -67% of the total ionization when X = OH

Table 2. CH, c.i. mass spectra of sulfides (2)'

X [RX.Hl' IR1' IRI+/RX.HI' PA(HX) Other ions (abundance)'

OH 19.3 66.8 3.4, 169 [M]'(6.6), 117{1.5) OCHZGCH 17.9 65.5 3.66 -185 [MI' (6.5), [MH-281' (1.7) NH2 51.8 26.1 0.50 201 [Ml'(5.0), [MH-28]'(1.4),

NHCeH6 68.4 13.5 0.20 210 [M]?(1.3),117(1.5) NHCHB 61.8 11.1 0.18 212 IMI'(7.2). [MH-28]'(1.1),

N(CHn)CeH, 61.7 7.0 0.11 216 [M]'(8.5), [M-H]+(1.5),

117 (1.7)

117 (1.8)

134 (2.2)

117 (1.9) NHCeH4CH3 65.9 5.0 0.075 216 [MI' (5.9). [M - HI' (3.8),

a Intensities as % total additive ionization. Mle 143.

[M.C$b]+ ( - 12%) and IMC,H,]+ ( -3%) not listed.

36 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 1, 1978

FRAGMENTATION IN CHEMICAL IONIZATION MASS SPECTROMETRY

Table 3. H, c.i. mass spectra of sulfoxides (2)' Table 5. H, c.i. mass spectra of sulfones (3)"

X (RX,Hl' [RI' [Rl'/[RX~Hl' PA(HX) Other ions (abundance)

OH 4.8 31.1 6.42 169 [M-H]'(25.7), 143(1.3),

OCHAkCH 7.6 60.8 8.02 -185 IM-Ol'(3.5). 131 (19.0) NHCsH. 3.9 64.2 16.46 210 [Mlf(8.7), IM-OH]'(7.3),

N(CH3)C.H. 6.6 51.7 7.8, 216 [M1'(1.9), [M-HI' (2.1), [MH-01' (4.6). 143 (9.5),

131 (32.6)

143 (2.2). 131 (8.7)

131 (3.7) NHCsHaCH. 6.3 38.2 6.07 216 [MH-01' (10.5). IMH-HzO]

(3.2). 143 (9.5). 131 (3.7)

a Intensities as % total additive ionization.

but only 5-7% when X is a methyl substituted anilino group where HX has a proton affinity -46 kcals mol-' higher than H20. Again the propargyloxy derivative (lc) appears out of line with the other results.

In the isobutane c.i. mass spectra of the sulfides only l b (X= OH) and l c (X = OCH,C%CH) showed sig- nificant ion signals for [R)+ (15% of total ionization for l b and 23% for lc) . In view of the CH4 c.i. spectra this result is not surprising. For all the sulfides the [RX-H]+ ion was the base peak and, apart from a small [C,H,]+ cluster peak, was the only peak ob- served in the spectra of the remaining compounds.

Mle 159.

Sulf oxides

In contrast to the sulfides discussed above and the sulfones (3) (see below), in the limited series of sulfox- ides (2) studied, the [R]+/[RX.H]+ ratio shows no consistent trend with changes in the proton affinity of the departing HX molecule. This is true for both the H2 c.i. results (Table 3) and the CH, c.i. results (Table 4). The reasons why the sulfoxides should be excep- tions to the inverse correlation between the extent of fragmentation by reaction (1) and the proton affinity of the leaving group are not entirely clear. However, there are other significant ion signals in many of the c.i. mass spectra, ranging from abundant mle 131 peaks [R-28]+ in the H, c.i. mass spectra of 2b and 2c, to abundant [MH - 01' peaks in the CH, c.i. mass spectra of 2f and 2g. Presumably, because of these competing and/or consecutive reactions the [R]+/[RX.H]+ ratio is no longer a good measure of the relative importance of reaction (1) as the functional group X is varied. This result tends to support Jardine and Fenselau's suggestion that the correlation will only

Table 4. C& c.i. mass spectra of sulfoxides (2)"

X [RX,Hl+ [Rl+ [R]'/[RX.Hl+ PA(HX) Other ions (abundancdc

OH 17.7 39.3 2.2, 169 [M- HI' (30.5) OCHZkCH 25.1 40.8 1.62 -185 [MH-28]'(2.5), 143 (2.7) NHC6Hs 23.1 50.9 2.20 210 IMl'(4.6). lMH-OI+(3.6),

N(CH3)CeHS 27.8 20.0 0.71 216 [MH-O]+(31.1), 143 (4.0) NHCsH4CH. 30.7 33.1 1.0. 216 [MH-OI'(11.8).

[MH-HzOl' (6.8)

[MH - Hz01' (2.8)

a Intensities as % total additive ionization. Mle 159. [M.C,H,]+ ( - lO0/o) and [M.C,H,]+ ( - 2%) ntensities not

listed.

X [RX,Hl'

OH 0.9 O C H z ~ C H 5.4 NH2 2.8

NHCH, 7.8 NHCeHs 8.3

N(CH3)CeHs 11 .O

NHCEH,CHj 9.0

~~

[R]+ IRI'/ERX~H]+ PA(HX)

68.2 75.8 169 93.0 17.2 -185 90.7 32.4 201 77.8 9.3, 210 79.5 10.2 212

68.5 6.2. 216

68.6 7.6, 216

Other ions (abundance)

159 (1.4), 149 (4.8). 147 (2.3)

149 (4.0). 147 (1.3) IMl'(5.3). 149 (2.3),94 (4.0) [MI* (1.7), IM- HI+ (5.8).

[MI' (2.4), IM - HI' (3.0),

[MI' (6.7), [M - HI+ (6.1 ),

149 (4.7)

159 (3.0). 134 (5.0)

149 (2.5). 134 (1.5) ~

a Intensities as % of total additive ionization.

be observed where other complicating fragmentation reactions are of minor importance. It also is possible that the sulfoxide spectra are more susceptible to variation with source and solids probe temperature since sulfoxides are notably unstable thermally.

In the isobutane c.i. mass spectra [RX.H]+ ac- counted for >95% of the total ionization in all cases.

Mle 175.

Snlfones

The main features of the H, and CH, c.i. mass spectra of the sulfones 3a-3g are summarized in Tables 5 and 6. By far the most important fragmentation reaction in both the H2 and CH4 c.i. systems is reaction (1). As shown in the Tables in both systems there is a consis- tent trend of decreasing fragmentation by reaction (l), as measured by the [R]+/[RX.H]+ ratio, with increas- ing proton affinity of the departing neutral HX molecule.

The isobutane c.i. mass spectra of the sulfones all showed [RX.H]+ as the base peak with only relatively minor fragmentation by reaction (1) for 3b-3d.

~~~ ~~ ~

CONCLUSION

The results obtained for the sulfides (1) and sulfones (3) provide strong support for the prediction made by Field' that the importance of reaction (1) should vary inversely with the proton affinity of the HX neutral product. This appears to be true even when the neutral expelled is large, as for the methyl substituted anilino derivatives studies. This is contrary to the suggestion made by Jardine and Fenselau, that the

Table 6. CH, c.i. mass spectra of sulfones (3)"

X [RX,HI+ [Rlt [RI'/lRX~Hl+

OH 1.9 42.8 22.5

OCH,C=CH 17.4 80.5 4.6. NHz 24.7 63.2 2.5. NHCsHs 38.5 31.0 0.81 NHCHj 62.0 20.3 0.32 N(CH3)C6Hs 67.6 16.0 0.24 NHCsHaCHj 55.4 20.3 0.3,

PA(HX) Other ions (abundance)'

169 159 (2.2), 149 (11.81, 143 (3.6). 103 (8.7). 85 (12.6)

-185 201 IMI'(1.9) 210 212 216 159 (3.91.218 (1.3) 216 [Ml'(5.4).IM-H1'(3.11

[MI' (4.0,178 (9.6). 94 (4.7) [MI* (2.6). IM - HI' (1.1 ), 116 (1.2)

- ~ ~~

a Intensities as % total additive ionization.

C[M,C,H5]' (-9%) and [M.C,H,]+ ( -2%) not listed. Mle 175.

ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 1, 1978 37

A. G. HARRISON AND F. I. ONUSKA

correlation only holds for small departing groups. The results obtained for the sulfoxides support Jardine and Fenselau’s conclusion that the correlation does not hold when complicating fragmentation reactions are significant, at least not if the importance of reaction (1) is measured by the [R]+/[RX.H]+ ratio.

Comparison of the c.i. mass spectra obtained for the sulfides, sulfoxides and sulfones show that, for the same X, the protonated sulfoxide ion is usually of lower abundance than the protonated molecule of the sulfide or sulfone, indicating that the protonated sul- foxide ions are considerably less stable than the other protonated molecules. Once again the spectra show the utility of isobutane c.i. in determining molecular

weights. H, c.i. shows extensive fragmentation and frequently the protonated molecular ions are too low in intensity for reliable molecular weight determina- tion, particularly if loss of a functional group as HX is facile. As has been observed previously, CH, c.i. yields ;M-H]+ ions of sufficient abundance for molecular weight determination as well as characteris- tic fragmentation useful in structure elucidation.

Acknowledgement

This work was supported, in part, by a grant from the National Research Council of Canada.

REFERENCES

1. F. H. Field, in Mass Spectrometry, ed. by A. Maccoll, Chapt. 5, p. 149. MTP Review of Science, Butterworths, London (1972).

2. 1. Jardine and C. Fenselau, J. Am. Chem. SOC. 98, 5086 (1976).

3. F. 1. Onuska and M. E. Comba and A. G. Harrison, Biomed. Mass Spectrom. 3, 248 (1976).

4. F. 1. Onuska and M. E. Comba, in preparation. 5. R. Yamdagni and P. Kebarle, J. Am. Chem. SOC. 98, 1320

(1976).

6. R. Yamdagni and P. Kebarle, J. Am. Chem. SOC. 95, 3504

7. F. M. Benoit and A. G. Harrison, J. Am. Chem. Soc.99.3980 (1973).

(1977).

Received 6 May 1977; accepted 8 July 1977 0 Heyden & Son Ltd, 1978

38 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 1, 1978