hydrogen migrations in mass spectrometry. vi—the chemical ionization mass spectra of substituted...

Hydrogen Migrations in Mass Spectrometry

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VI-The Chemical Ionization Mass Spectra of Substituted Benzoic Acids and Benzyl Alcohols?

79 D C W H -

- HZ

123 [ M H P - 105

I 1 I 1

D C O O H 123 rMHlt -

C”4 - 79 105

I I ‘ 1 I I I

Hiroshi Ichikawa and Alex. G. Harrison8 Department of Chemistry, University of Toronto, Toronto, Canada M5S 1 A l

The Hz and CH, chemical ionization mass spectra of a series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H,O or elimination of CO,, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [ME€]+ involve loss of H,O or CH,O, analogous to the CO, elimination reaction for the benzoic acids. It is shown that the CO, and CH,O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discemible effect of substituents on the fragmentation of [MH]+ is an enhancement of the H,O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carbogyt function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H,O elimination. Apparently, this route is favoured over the direct elimination of H,O from the aubonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.

INTRODUCTION

A prominent feature in the electron impact (EI) mass spectrum of benzoic acids and benzyl alcohols having an ortho substituent bearing one or more hydrogen atoms is a pronounced peak corresponding to the loss of H,O from the molecular ion. These fragmentation processes represent specific examples of the so-called ortho effect’ pictured by the general reaction.

m/e

Figure 1. H, and CH, CI mass spectra of benzoic acid.

The present work reports a study of the H, and CH, chemical ionization (CI) mass spectra of a series of substituted benzoic acids and benzyl alcohols under- taken as part of a programme to study substituent effects in CI mass spectra and, particularly to determine if the ortho effects observed in EI mass spectra also are observed in CI mass spectra.

Chemical ionization mass spectra of benzoic acids

The H, and CH, CI mass spectra of benzoic acid are shown in Fig. 1. In the H, CI mass spectrum the [MH]+ ion intensity is low, with the base peak being mle 79, [C,H,]+, corresponding to loss of CO, from

t For Part V, see Ref. 4. t Address correspondence to this author.

[MH]+. The only other significant fragment ion is the benzoyl ion, [MH-H20]+, at mle 105. Although studies of the D, CI mass spectrum of benzoic acid were complicated by a small amount of deuterium incorporation in the benzoic acid, presumably as the result of some type of exchange reaction, the results did show that the [C,H,]+ product incorporated both the added proton and the hydrogen of the carboxyl group, while in the formation of the benzoyl ion the added proton and the carboxyl hydrogen were largely contained in the neutral fragment, the extent of inter- change with the aromatic ring hydrogens being less than 10%.

The same fragment ions are observed in the CH, CI mass spectrum of benzoic acid although the [MH]+ ion intensity is much greater and the fragment ion intensities, particularly [C,H,]+, are much lower as a result of the less exothermic protonation in the CH, CI system. The results suggest the fragmentation reactions outlined in Scheme 1, where it is proposed that

@ Heyden & Son Ltd, 1978

003~493X/78/0013-0389$04.00

ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 389

H. ICHIKAWA AND A. G. HARRISON

'@++ - H,O

+ co,

A+ \ H+

Scheme 1

the CO, elimination reaction proceeds from the ring protonated acid, while the H 2 0 elimination reaction proceeds from the carboxyl protonated acid.

Although loss of H,O from [MH]+ is a common reaction in the CI mass spectra of carboxylic acids? as is loss of ROH in the CI mass spectra of esters R'C0,R?3 loss of carbon dioxide, involving migration of the carboxyl hydrogen, is an unusual reaction which is not observed in the CI mass spectra of alkanoic acids., Therefore, it was of interest to determine the structural requirements for the migration reaction and whether groups larger than hydrogen are capable of migration. As shown in Fig. 2, the [MH-C02]+ ion (mle 93) is the base peak in the H2 C1 mass spectrum of methyl benzoate and also is observed, with low intensity, in the CH, CI mass spectrum of methyl benzoate, indicating that a methyl group is capable of migration in the CO, elimination reaction. Also shown in Fig. 2 are the H, and CH, CI mass spectra of phenyl benzoate. Although, in both spectra, the major fragmentation of [MH]' involves loss of phenol, leading to formation of [C6H5CO]+ (mle 105), a low intensity signal is observed at mle 155 corresponding to protonated biphenyl, the product of CO, elimination from [MH]+. Thus, even phenyl groups are capable of migration although the tendency is greatly re- duced. The H2 CI mass spectra of a-picolinic acid, methyl nicotinate and methyl isonicotinate showed

Q-COOCH,

I I . I55 0 , I I I I I 1 60 I00 I40 I80 220

m / e

Figure 2. H, and CH, CI mass spectra at methyl benzoate and phenyl benzoate.

peaks corresponding to [MH-CO,]' which were, respectively, 6, 20 and 14% of the base peak ([MH- ROH]'), while in the H, CI mass spectrum of 1- naphthylcarboxylic acid the [MH - CO,]+ ion formed the base peak. Clearly H or CH, migration to the pyridyl and naphthyl aromatic rings occurs readily. To investigate whether the presence of an a-p double bond was sufficient to induce the migration reaction leading to CO, elimination, the H, and CH, CI mass spectra of methyl acrylate, methyl methacrylate, methyl cinnamate and cinnamic acid were examined. The complete CI mass spectra of these compounds will be discussed in detail in a further paper. Elimination of CO, from [MH]+ was detected (as a minor process) only in the H, CI mass spectra of methyl cinnamate and cinnamic acid. It thus appears that the presence of an aromatic ring system is essential to the migration reaction and a-p unsaturation, unless conjugated with an aromatic ring system, is not a sufficient structural criterion for reaction. These results strongly suggest that the migration reaction is a consequence of protonation at the aromatic ring followed by migration of the H or R group of the carboxyl function to the aromatic ring [reaction (2)]. The driving force for the rearrangement undoubtedly is the stability of the protonated aromatic species formed, as well as the ther- mochemical stability of the CO, neutral.

Interestingly, the CI mass spectra of phenyl acetate and 1-naphthyl acetate showed no peaks corresponding to [MH-CO,]+. One would anticipate some protonation of the aromatic ring; however, it appears that a methyl group attached to carbon is not capable of migration to a protonated aromatic ring, but rather only groups attached to oxygen as in reaction (2). Reaction (21) is not observed for alkyl groups, R, larger than methyl but rather for larger alkyl groups. H migration with olefin elimination to form protonated benzoic acid becomes an important fragmentation reaction?

The H, CI mass spectra of the substituted benzoic acids examined are summarized in Table 1. For the CH,, OH and NH, substituted acids the major fragmentation reactions are as outlined in Scheme 1 for benzoic acid. However, for the halogen substituted acids intense fragment ions are observed at mle 77

depending upon the substituent. Pressure variation studies of the H, CI mass spectra of the halobenzoic acids show' that the formation of these products can be explained by the reaction sequence of Scheme 2, involving.the elimination of X (Br and I) from [MH- CO,]' to form [C,H.$, or elimination of HX (all halogens) from [MH-CO,]' to form [C,H,]+, which then adds to H, to form [C,H,]'. The increasing yield of [C6H6]+ over [C6H5]++[C,H,]+ for the bromo and

([C&]'), m/e 78 ([C,&]') and m/e 79 ([C,H,+),

390 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 @ Heyden & Son Ltd, 1978

HYDROGEN MIGRATIONS IN MASS SPECTROMETRY-VI

Table 1. H2 CI mass spectra of substituted benzoic acidsa

Substituent [MHl+ IMH-COd+ [MH-H201f (CHs1' IGHel' [CeH71+ Other ions (intensity)

- - [MIt (5) 91(8), 79(2) - - (MI' (9),91(9), 79(15) - - [MIt (4),91(9), 79(4)

- - [MI? (6). 79(19)

0-CH, 28 100 20 - m-CH, 20 100 20 - P-CH, 37 100 24 - 0-OH 7 8 1 00 m-OH 30 100 37 - p-OH 39 100 37 - - - [Ml?(11),79(14) 0-NH, 10 51 100 - - - [Ml?(18), 119(7) m-NH, 22 100 25 P-NH, 47 100 61 0-F 63 71 100 11 - 20 [M]+(lO), 121(6)b m-F 22 100 27 6 - 47 [MI+ (7). 121(6)b P-F 52 100 56 5 - 33 [Ml*(16), 121(5)b 0-CI 55 39 100 11 - 44 [Ml?(9) m-CI 40 100 39 18 - 93 [Ml?(6) p-CI 50 100 48 22 - 96 [M]?(10) o-Br 39 29 100 13 23 96 123(12)c m-Br 41 74 74 16 32 100 123(6)c p-Br 39 52 70 11 24 100 123(13)c 0-1 17 <I 100 - 38 32 [MI+ (14). 122(11)d, 123(10) m -I 14 2 14 - 100 30 [MF (ll), 122(26)d, 123(8)

120(6), 79(2) - - -

- [MI? (17) [MI? (1 2)

- - - - -

Intensities as % of base peak. [MH-HFl+. [MH-HBr+H,]. [MH-I]+.

iodo compounds is in agreement with the trend ob- served6*' in the H2 CI mass spectra of the halobenzenes and halotoluenes. The low intensity m/e 79 ([C,H,]') ion signals observed in the H, CI mass spectra of the methyl and hydroxy substituted benzoic acids were shown, by H, pFessure variation studies, to originate in the same fashion (Scheme 2, X = CH, or OH). The H, CI mass spectra of toluene and phenol also show low intensity ion signals at mle 77 ([C6H5]+) and m/e 79 ([C,H,]+), with the latter ion originating by reaction of [C,H,]+ with H,. Other minor ions observed in the H, CI mass spectra besides the [MI' ion originating by charge transfer from [HJ, are [MH-HF]+ (m/e 121) for the fluorobenzoic acids, [MH - HBr + H,]+ (m/e 123) for the bromobenzoic acids and both [MH-IF (m/e 122) and [MH-HI+ H,]+ for the iodobenzoic acids.

The CH, CI mass spectra of the substituted benzoic acids are summarized in Table 2. The [MH]+ ion is the base peak in all spectra, except that of o- aminobenzoic acid, while the major fragmentation reactions of [MI-€]+ are loss of H,O and loss of CO, as outlined in Scheme 1. The cluster ions [M.C,H,]+ and [MC2H5]+ were present in all spectra, with intensities >5% of the base peak in several spectra. Of particu- lar interest are the ions at mle 149 for salicylic acid

Y' I;I'

Scheme 2


and m/e 148 for anthranilic acid with intensities 14 and 9% of the base peak, respectively. In the CD, CI mass spectra these peaks shifted upwards by five mass units. The formation of these products, which correspond to H,O elimination from [M.C,H,]+, can be rationalized by attack of [C,H,]+ at the ortho substituent, as shown in reaction (3). Similar reactions were not observed for the meta and para derivatives.

The only other significant ion signals observed in the CH, CI mass spectra were the low intensity [C,H,]+ (m/e 93) ions for the fluorobenzoic acids, which may originate either by the direct reaction of [CH,]+ with the neutral molecule [reaction (4)] or by loss of HF from [MH-CO,]+ followed by reaction of [C6H5]+ with CH, [reaction (5)]. Both reactions have been observed in the CH, CI of simpler halobenzenes.'

ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 391

H. ICHIKAWA AND A. G . HARRISON

a0

40-

a0

- s - - z 40- r

L o - al c

._

c .- : 80-

rr" 40-

0 - ._ c -

ao-

40-

0

Table 2. CH, CI mass spectra of benzoic acidsa

Substituent IMHI+ IMH -COzI+ [MH -HzOI' Other ions (intensity)

0-CH, 100 24 26 [M*C,H51+ (91, [MI' (61, [M.C2H5-CO21+ (6) m-CH, 100 9 15 [M.C,H,]+ (9). [MI' (16), [M.C,H,-CO,]+ (4) P-CH, 100 11 14 [M*C2H51+ (91, [MI' (61, [M-CZH5-CO21+ (4) 0-OH 100 3 23 [M*C2H5+-H,01 (141, [MI' (7). [MX2H5-C021+ (3) m-OH 100 10 11 [M*C,H51+ (6). [MI' (61, [M.C,H5-C0,1+ (6) p-OH 100 12 12 [M.C2H51+ (6). [MI' (6), [M.C2H5-CO21+ (5) 0-NH, 61 19 100 [M.C2H5- H,OI+ (91, [MI' (15). [M.C,H5-C02]+ (14) m-NH, 100 12 13 [M.C2H51+ (51, [MI' (71, [M*C2H5-C02]+ (7) P-NH, 100 9 14 [M.C,HJ (10). [MI' (7). [M.C2H5-C02]+ (6)

m -F 100 8 12 [MI' (8), [M.C,H5-CO,]+ (3). [GH,]' (20) P-F 100 1 2 26 IM.C2H51+ (61, [M1'(15), IM.C,H5-C0,1+ (16). [&Hg]+ (12)

rn -CI 100 5 13 [M.CZHJ+ (5). [MI' (7) p-CI 100 13 17 [M.C,HJ+ (5). [MI' (8)

0-F 100 4 33 [MI' (101, [GHgl+ (2)

0-CI 100 5 23 [M.C,H51+ (1.51, [MI' (9)

o-Br 100 5 21 [M.C,H,I+ (21, [MI' ( lo) , 123(5) m -Br 100 11 13 [M.C,H,]+ (5). [ M l + ( l l ) , 123(3) p-Br 100 8 15 [M*C,H,l+ (51, [MI' (6), 123(15) 0-1 100 < I 37 [MI' (12) [MH - I]' (20), [C6H5]+ (8) m-l 100 5 10 [Ml'(12) [MH-I]'(26) [C6H5COIt (9). [C,H6]'(20)

- 91 Q - C H P - H2

79 - -

I I 1,109 hH1'

- 91 Q - C H ~ H - CH4 -

79

I 1!09"IHI'

'07 &&OH -

[MH]?125 - 93

HZ

I I I, 1,,124

107 &D@H - - CH4 [MH]+: 125 - 93

I I I 124 I I I I I

a Intensities as % of base peak.

In the CH, CI mass spectra of the iodobenzoic acids the ion signal at mle 122 corresponds to [MH - I]+, a fragmentation observed7 for simpler iodobenzene derivatives, while [C,H6]+ may originate by further loss of CO, from this fragment.

Chemical ionization mass spectra of benzyl alcohols

Figure 3 shows the H, and CH, CI mass spectra of benzyl alcohol. In both systems the base peak is observed at rnle 91, corresponding to the [GH,]' ion originating by H,O loss from [MH]+. An additional important fragment ion in both spectra is observed at mle 79 corresponding to loss of CH,O from [MH]+,

analogous to the CO, elimination reaction in the benzoic acid systems. The H, and CH, CI mass spectra of o-methylbenzyl-a,a -d, alcohol, also presented in Fig. 3, show fragment ions at rnle 107 ([MH -H,O]+) and mle 93 ([MH - CD,O]+), indicating the reaction scheme illustrated in Scheme 3. As the data in Tables 3 and 4 show, this is a fragmentation scheme which is common to all the benzyl alcohols studied.

To examine the scope of the formaldehyde elimination reaction the H2 CI mass spectra of a number of a-P unsaturated alcohols were examined. Although rnle 43 ion signals are observed in the H, CI mass spectra of crotyl and methallyl alcohols (Fig. 4), corresponding nominally to [MH - CH,O]+, there also are significant ion currents at mle 71 ([M-HI'), and it is possible that the mle 43 ion signals originate by the fragmentation rnle [71]++ rnle [43]++28, a fragmentation reaction which is known to occur in the EI ionization mass spectra of unsaturated alcohols? How- ever, the ion signal at mle 105 in the H, CI mass spectrum of cinnamyl alcohol (Fig. 4) does correspond to loss of CH,O from the [MH]+ ion. In the deuter- ated cinnamyl alcohol, C,H,CHCHCD,OH peaks were observed corresponding to [MH - CD,O]+ (259'0), [MH-CHDO]+ (99'0) and [MH-CD,O]+ (2.5%), indicating that the formaldehyde loss, although largely involving elimination of the CH,O of the alcohol function, is not as specific as for the benzyl alcohols. It appears that the requirement of a conjugated aromatic system, observed in the CO, elimination reaction in acids, applies also to the CH,O elimination reaction in alcohols. For the benzoic acid derivatives it was found that, in addition to hydrogen, methyl groups and, to a minor extent, phenyl groups, were capable of migration. This is not the case for the formaldehyde elimination reaction, since the H, CI mass spectrum of benzyl methyl ether shows no peak corresponding to [MH - CH,O]+. However for a - substituted benzyl alcohols, C6H,CHROH, loss of the

392 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 Heyden & Son Ltd, 1978


Table 3. €I2 CI mass spectra of substituted benzyl alcohols'

Substiiuent IMHI+ IMH-CHZOl+ [MH-HzO]+ Other ions (intensity)

0-CH, < 1 1 0 0 86 [MI+ (8). [M-Hl+ (18). [GH,l+ (31, C,H,+ (5) m-CH, 1 91 1 0 0 [MI+ (101, [M-Hl+ (24). [C,H,l+ (10). [C,H,]+ (11) P-CH, 1 83 1 0 0 [MIf (101, [M-Hl+ (231, [GH,I+ (3). [C6H71+ (5) 0-OH 2 37 1 0 0 [MI+ (141, [C&l+ (15) m-OH 8 54 1 0 0 [MI+ (13). [C,H,l+ (15) p-OH 1 0 8 1 1 0 0 [MI+ (1 11, [C6H71+ (25) 0-NH, 1 5 81 1 0 0 [Ml+(51), [M-HI+ (11) m-NH, 1 8 58 1 0 0 [Ml+(28), [M-HI+ (11) P-NH, 1 5 67 1 0 0 [MI' (271, [M-HI+ (18)

a Intensities as % of base peak.

aldehyde RCHO from [MH]' is observed, the approp- riate ion signals being observed in the H, CI mass spectra of a-methyl benzyl alcohol and benzhydryl alcohol.

The H, CI mass spectra of the methyl substituted benzyl alcohols (Table 3) show significant ion signals corresponding to [M - HI+, presumably resulting from elimination of H2 from [MH]+ (the major fragmentation reaction in the H, CI mass spectrum of toluene'), as well as low intensity ion signals at m/e 91, presumably resulting from H, loss from the [MH-CH,O]+ ion. In addition, both the methyl and hydroxy substituted alcohols show ion signals at m/e 79 ([C6H7]+) which, from pressure studies, were shown to originate by reaction of [C,H,]+ with H,, indicating the reaction sequence.

Y'

The CH, CI mass spectra of the benzyl alcohols showed moderately abundant ion signals at a mass corresponding nominally to [M - HI+; however, exper- iments using CD, as a reagent gas showed that the major part of this ion signal corresponded, in fact, to [M-C2H, - CH,O]+ and it is thus reported in Table 4. In addition, for the hydroxy and amino substituted benzyl alcohols, ion signals were observed corresponding to [M-C2HS-H,0]+. The intensity of this ion signal was much greater for the o-OH and 0-NH, substituted alcohols, indicating an ortho effect similar

to that observed for the ortho substituted benzoic acids as outlined in reaction (3).

Substituent effects in chemical ionization mass spectra

Table 5 records the [MH - CO,]+/[MH]+, [MH - H,O]+/[MH]+ and [MH - H,O]+/[MH - CO,]+ ratios recorded in the H, CI mass spectra of the benzoic acids, while Table 6 records the same intensity ratios recorded for the CH, CI mass spectra. For the halobenzoic acids the [MH - CO,]' intensities used for the H, CI mass spectra include the [C,H,]+, [C,H,$ and [C6H7]+ ion intensities resulting from further fragmentation of [MH -CO,]' (see above discussion). Table 7 records the [MH - H,O]+/[MH - CH,O]+ ratios observed in the H, and CH, CI mass spectra of the benzyl alcohols studied.

The only effect of substituents on the CI mass spectra that can be discerned clearly from these intensity ratios is the increased loss of H,O from [MH]' in the benzoic acids when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This 'ortho' effect is evident from the increased [MH- H,O]+/[MH]+ and [MH - H,O]+/[MH - C02]+ ratios observed (Table 5 and 6) for these ortho substituted compounds. Although this 'ortho' effect superficially resembles the ortho effect observed in the EI mass spectra of substituted benzoic acids and benzyl alcohols [reaction (l)] there are distinct differences. The most noticeable is that there is no specific ortho effect in the CI mass spectra of the benzyl alcohols, in contrast to the EI mass spectra where the ortho effect is observed for both benzoic acids and benzyl alcohols. Second, an o-CH, group does not lead to an enhanced loss of H 2 0 from [MH]' for the benzoic acids in the

Table 4. CH, CI mass spectra of substituted benzyl alcohols'

Substiiuent

0-CH,

P-CH, 0-OH

m -CH,

m-OH p-OH 0-NH, m-NH, P-NH,

IMHI+

< 1 2

< 1 6

37 31 26 22 8

[MH-CHzOI+

45 30 27 20 1 9 29 46 11 8

IMH-HzOl+

1 0 0 1 0 0 1 0 0 100 1 0 0 1 0 0 1 0 0 1 0 0 1 0 0

a Intensities as % of base peak

Other ions (intensitv)

[MI+ (5). [M.C2H5-CH20]+ (12) [Ml'(7), [M.C2H5-CH20]+ (11) [MI+ (61, [M*C2H5-CH,0]+ (12) [M.C2Hs-H20]+ (14), [MI' (8), [M.C,H5- CH,Ol+ (10) [M*C,H5-H20]+ (51, [MI' (8). [M~C,H,-CH,O]+ (16) [M.C,H5-H,Ol+ (4). [MI' (7), [M*C,H5-CH,01+ (18) [M.C2H6-H201+ ( lo ) , [MI+ (20), [M~C,H5-CH,01' (17) [M.C,H5- H,O]+ (4), [MI' (1 l ) , [M*C,H,-CH,O]+ (10) [M.C,H5- H,O]+ (2), [MI+ (26). [M.C,H,-CH,O]+ (6)

@ Heyden & Son Ltd, 1978 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 393


80

H+ Hf

55 CH3-CH=CH -CH;PH

Scheme 3

- $

.- 3 80- Y

c c

40- al .- c 0 -

00- B

CI mass spectra, although it does lead to an enhancement of the H20 loss peak in the EI mass spectra. Finally, we note that an ortho halogen substituent leads to an enhanced [MH-H,O]+ peak in the CI mass spectra of the benzoic acids, while ortho halogens obviously do not promote H,O loss in the EI mass spectra. These observations indicate that the 'ortho' effect observed in the CI mass spectra of benzoic acids has a different origin from the ortho effect observed in EI mass spectra [as exemplified by reaction (l)].

For the benzoic acids, protonation by [H3]+ or [CH5]+/[C2H5]+ may occur at any one of the four sites indicated in a, while protonation of benzyl alcohol may occur at any one of the three sites, 1, 3 and 4, indicated in b. Protonation of either compound at site 1 or site 3 should not lead to any enhancement of H,O

-43

l.+2

CH3 - 55 C+=&-CH~OH

H2 - [MHI'; m/e 73

43 I ,72

C6H5CH=CH CH20H 117 -

2 0 OH

a b C

loss by an ortho substituent, while protonation at site 4 could lead to enhanced loss of H,O, but for both benzoic acids and benzyl alcohols, when the substitu- tent is in the ortho position. (However, note that protonation at the substituent would explain the lack of enhancement of H20 loss by o-CH, since protonation of substituents should occur only for those substituents bearing unshared electron pairs.) Thus, it

40 L I H2 [MH]'; m/e 73

40

0 50 70 90 I10 I30

m /e

Figure 4. H, CI mass spectra of crotyl, methallyl and cinnamyl alcohol.

appears that the 'ortho' effect observed for the benzoic acids must be related to protonation at the carbonyl oxygen (site 2, structure a). For the carbonyl protonated acid, c, to lose H,O requires a suprafacial [ l , 31 hydrogen migration, and there is substantial evidence that such a migration does not occur readily because it is symmetry forbidden and consequently has a high activation energy barrier. Thus, we suggest that the enhancement of the H,O elimination reaction by ortho substituents may represent an intramolecular catalysis of proton transfer from one oxygen to the other in the resonance stabilized ion c. This is illustrated in Scheme 4. It should be noted that the suprafacial [1,5] hydrogen migrations implicit in Scheme 4 are symmetry allowed and would not be expected to have an activation energy greater than the reaction endothermicity. The mechanism proposed also rationalizes the experimental observations that enhancement of H,O loss is observed only for benzoic acids and only when a substituent bearing a lone pair of electrons, capable of accepting a proton, is in the ortho position. Although the interpretation of the D, and CD, CI mass spectra was complicated by exchange reactions, it was clear that for the o-OH and o-NH, substituted acids the added deutron was retained in the ionic product a

Table 5. Intensity ratios in €I2 CI mass spectra of benzoic acids'

[MH-C021+ [MH-H,OI+ [MH- H201+

[MHI+ [MHI+ [MH-C021+ Substituent

H o-CH, m-CH3 P - C H ~ 0-OH m-OH p-OH 0-NH,

p-NH 0-F m-F P-F 0-CI m-CI p-CI o-Br m-Br p-Br 0-1 m -I

m-NH,

5.6 3.6 5.0 2.7 1.1 3.3 2.6 5.1 4.5 2.1 1.6, 7.0 2.7 1.7 5.3 4.4 4.1 5.4 4.8 2.4 9.4

1.6 0.7, 1 .o 0.6,

14.3 1.2 '1.3

10.0 1.1 1.3 1.6 1.2 1.1 1.8 0.9 1 .o 2.6 1.8 1.8 5.9 1 .o

0.28 0.20 0.20 0.24

0.37 0.49

0.24 0.61 0.98 0.18 0.41

0.19 0.22 0.62 0.33 0.37 2.4 0.1 1

12.5

1 .9,

1 .o,

a For halogen substituents [MH-CO,l+ intensity includes further decomposition products (Scheme 2).

394 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 @ Heyden & Son Ltd, 1978


Table 6. Intensity ratios in CH, CI mass spectra of benzoic aads

[MH -COzlf [MH - H201f [MH - HzOl+ [MHI+ [MHlf [MH -coal+ Substituent

H 0.07, 0.1 1 1 *4 0-CH, 0.24 0.27 1.1,

P-CH, 0.1 1 0.14 1.2,

m-OH 0.09, 0.1 1 1.1, p-OH 0.12 0.12 1 .o, 0-NH, 0.31 1.64 5.2, m-NH, 0.12 0.13 1 .o,

m -F 0.08, 0.12 1 *4 P-F 0.12 0.26 2.1, 0-CI 0.05, 0.23 3% m -CI 0.07, 0.13 1.7, p -CI 0.13 0.16 1.2, o-Br 0.05, 0.21 3.9, m-Br 0.10 0.13 1.3, p-Br 0.07, 0.15 1.9, 0-1 <0.01 0.37 > 37 m-l 0.05 0.10 1 .o

m-CH, 0.09, 0.15 1 .6,

0-OH 0.03, 0.23 7.1,

P-NH, 0.04 0.14 1.6, 0-F 0.04, 0.33 8.0,

significant fraction of the time. This also is consistent with the proposed mechanism.

The rationale presented above assumes that a significant fraction of the proton transfer reactions from [H3]+ and [CHJ/[C,H,]+ to the benzoic acids involve protonation of the carbonyl oxygen. Therefore, a brief discussion of the energetics of protonation of benzoic acids and benzyl alcohols appears desirable. From 0 (Is) ionization energy-proton affinity correlations'' one may derive a proton affinity of -164 kcal mol-' for the oxygen of benzyl alcohol. For benzenes bearing the substituents employed in the present work, the aromatic ring proton affinities have been found" to be in the range 180 kcal mol-' (halogen substituent) to 209 kcal mol-' (NH, substituent), with the proton affinity of the substituent being lower (for example, the oxygen proton afinity of anisole is -180 kcal mol-1 compared with 199 kcal mol-1 for the aromatic ring"). Clearly, for the benzyl alcohols the thermodynamically favoured site of protonation will be the

Table 7. Intensity ratios in CI mass spectra of benzyl alcohols

Substituent

H 0-CH, m-CH, P-CH, 0-OH m-OH p-OH 0-NH, m-NH, P-NH,

0.86 1 .o, 1.2,

1 .% 1.2, 1 .2, 1.7, 1.5,

2.7,

CHI CI

2.5, 3.3, 3.7,

5.3, 3.5, 2.2, 9.0,

11.9,

5.0,

OH

a!++ \ Y H,O

Scheme 4

aromatic ring. The proton affinity of benzoic acid has not been reported. However, from the PA-0 (1s) ionization energy correlations" one may derive a PA of -200 kcal mol-' for the carbonyl oxygen of methylbenzoate compared with a proton affinity of -170 kcal mol-' for the ether oxygen. The proton affinities of the similar oxygens in benzoic acid should not be greatly different. Thus, for most benzoic acids, protonation at the carbonyl oxygen should be either thermodynamically favoured or thermodynamically competitive with protonation of the aromatic ring. However, since PA(H,) = 101 kcal mol-' l3 and PA(CH,) = 128 kcal mol-' 13, protonation of any of the sites indicated in a and b will be strongly exothermic. Indeed, the initial site of protonation probably is dictated more by kinetic considerations than by ther- modynamic considerations. Nevertheless, significant protonation at the carbonyl oxygen clearly is possible.

EXPERIMENTAL

Chemical ionization mass spectra were obtained using a Dupont 21-490 mass spectrometer equipped with a high pressure source. Reagent gas pressures were 0.2- 0.5 Torr and the spectra were obtained at a source temperature of - 150 "C. Liquid samples were intro- duced through the heated inlet system at a temperature of - 100 "C, while solid samples were evaporated directly from the direct insertion probe using the minimum probe temperature necessary for adequate ion currents.

Unlabelled reagent gases and substrate compounds were commercial compounds of high purity. Methane- d, was obtained from Merck, Sharp and Dohme, Montreal while D, was obtained from Matheson and Co. Benzyl alcohol-a-a-d, and cinnamyl alcohol-1,l- d, were prepared by reduction of the corresponding acids with LiAlD,.

Acknowledgements

The authors are indebted to the National Research Council of Canada for financial support. H. I. gratefully acknowledges the sabbatical leave provided by the Hoshi College of Pharmacy.

@ Heyden & Son Ltd, 1978 ORGANIC MASS SPECTROMETRY, VOL. 13, NO. 7, 1978 395


REFERENCES

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3. C. W. Tsang and A. G. Harrison, J. Chem. SOC. Perkin Trans. 2 1718 (1975).

4. F. M. Benoit and A. G. Harrison, Org. Mass Spectrom. 13, 128 (1978); H. lchikawa and A. G. Harrison, in preparation.

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3980, (1977).

(1976).

Received 5 December 1977; accepted 2 February 1978


hydrogen migrations in mass spectrometry. vi—the chemical ionization mass spectra of substituted...

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