Intramolecular electrophilic aromatic substitution in gas-phase-protonated difunctional compounds containing one or two arylmethyl groups

Article abstract of DOI:10.1002/jms.537

A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical ionization and collision-induced dissociation of their MH⁺ ions, whereby a new bond is formed between the two benzyl groups, giving rise to abundant [C₁₄H₁₃]⁺ (m/z 181) ions. This rearrangement has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an ion-neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A similar highly efficient intramolecular electrophilic substitution takes place in di-α- and β-naphthylmethyl adipates affording m/z 281 [C₂₂H₁₇]⁺ ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient rearrangement occurs in benzyl α- and β-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl α- and β-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of the O - R bond heterolysis of the protonated functionalities, the ability of the neutral R′ groups (non-dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic substitution processes and the electrophilicity of the R⁺ ions. Copyright

Full text of DOI:10.1002/jms.537

JOURNAL OF MASS SPECTROMETRY
J. Mass Spectrom. 2003; 38: 1169–1177
Published online 29 October 2003 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jms.537
Intramolecular electrophilic aromatic substitution in
gas-phase-protonated difunctional compounds
containing one or two arylmethyl groups
M. Edelson-Averbukh and A. Mandelbaum∗
Department of Chemistry, Technion–Israel Institute of Technology, Haifa, Israel
Received 23 May 2003; Accepted 15 August 2003
A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical
ionization and collision-induced dissociation of their MH+ ions, whereby a new bond is formed
between the two benzyl groups, giving rise to abundant [C14H13]+ (m/z 181) ions. This rearrangement
has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an
ion–neutral complex formed by the cleavage of one of the benzyl–oxygen bonds. A similar highly efficient
intramolecular electrophilic substitution takes place in di-a- and b-naphthylmethyl adipates affording m/z
281 [C22H17]+ ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient
rearrangement occurs in benzyl a- and b-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl a-
and b-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient
in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl
and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior
of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of
the O — R bond heterolysis of the protonated functionalities, the ability of the neutral Rꢀ groups (non-
dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic
substitution processes and the electrophilicity of the R+ ions. Copyright  2003 John Wiley & Sons, Ltd.
KEYWORDS: aromatic electrophilic substitution; rearrangements; intramolecular interactions; benzyl derivatives;
difunctional compounds; ion–neutral complexes; chemical ionization; collision-induced dissociation; stereochemical effects
and collision-induced dissociation (CID) conditions.13,14 This
rearrangement involves an intramolecular C—C bond for-
mation between the two benzyl groups giving rise to
abundant [C14H13]C (m/z 181) ions. A CID study of the
[C14H13]C ions has shown that they are an almost equimo-
lar mixture of isomeric ˛-o-tolylbenzyl, ˛-p-tolylbenzyl and
p-benzylbenzyl cations in all cases. In contrast to the diben-
zyl diesters, diethers and ether esters, this rearrangement
reaction is insignificant in protonated sulfur analogues,
and absent in the nitrogen-containing derivatives (benzyl-
diamines, -diamides and -aminoamides).15 The proposed
mechanistic pathway for this rearrangement process is
shown in Scheme 1. The initial step in this mechanism
is the cleavage of the benzylic C—O bond of the pro-
tonated ether or ester function to form an ion–neutral
complex16–20 A, followed by the electrophilic attack of the
benzyl cation at the ortho and para positions of the neutral
benzyl group (non-dissociated from the oxygen function)
within the ion–neutral complex, resulting in the two ꢀ-
complexes B1 and B2. Intramolecular proton transfers from
the ipso positions to the oxygen atom and the heterolytic
fission of the second benzyl–oxygen bond afford the ˛-
o-tolylbenzyl, ˛-p-tolylbenzyl and p-benzylbenzyl cations
a, b and c. The proposed mechanism resembles that of
INTRODUCTION
A great part of the fragmentation processes occurring in
organic ions in the gas phase involves intramolecular for-
mation of new bonds between originally non-bonded atoms.
Such rearrangements have been of interest since the early
days of organic mass spectrometry, and a large amount of
work has been invested in the exploration of their mech-
anistic pathways.1–4 Rearrangement processes may create
pitfalls in structural assignments of unknown materials by
mass spectrometry. On the other hand, they are the basis
of many stereochemical effects in mass spectrometry, which
may facilitate configurational assignments of stereoisomers
by this technique.5–9 In certain cases meaningful correlations
have been found between rearrangement processes of gas-
phase ions under chemical ionization (CI) conditions and
acid-catalyzed molecular rearrangements in solution.10–12
We have recently reported a highly efficient rearrange-
ment process occurring in a large number of gas-phase
protonated benzyl diesters and diethers under isobutane-CI
ŁCorrespondence to: A. Mandelbaum, Department of Chemistry,
Technion–Israel Institute of Technology, Haifa, Israel.
E-mail: chr17am@techunix.technion.ac.il
Contract/grant sponsor: Fund for Promotion of Research at the
Technion.
Copyright  2003 John Wiley & Sons, Ltd.

1170
M. Edelson-Averbukh and A. Mandelbaum
the aromatic electrophilic substitution in the condensed
phase.
in the GC/MS analyses of the six stereoisomeric pairs 1–6. CI
measurements were performed at an ion source temperature
°
of 150 C and 0.4 Torr (indicated) reagent gas pressure (isobu-
tane, acetonitrile) ꢁ1 Torr D 133.3 Paꢂ. CID measurements
were performed with argon as the target gas (0.3 mTorr,
indicated) at 30 eV collision energy (indicated). All the data
presented in each table were obtained on the same day under
identical conditions, in order to ensure reliable comparisons.
H
+
Y
CH2
CH2
YH
+
CH
Y
2
CH2
Y
Y = COO; -O-
ion/neutral
complex A
Materials
Diesters 1–3, 6, 8, 9, 12 and 13 were synthesized by
esterification of cis- and trans-1,4-cyclohexane dicarboxylic
and adipic acids by the corresponding alcohols (or by a
mixture of the alcohols in the cases of 1–3, 6, 8 and 9)
in the presence of a catalytic amount of p-toluenesulfonic
acid monohydrate.21 1- and 2-naphthalenemethanols were
prepared from 1- and 2-naphthoic acids by reduction with
lithium aluminum hydride.22
YH
YH
CH2
+
H
CH2
CH2
H
CH2
+
+
Y
Y
σ-complex B1
σ-complex B2
Cis- and trans-1-benzyloxymethyl-4-tetrahydropyran-
oxymethylcyclohexanes (4) were synthesized by par-
tial etherification of cyclohexane-1,4-dimethanol (cis and
trans mixture) to afford cis- and trans-1-benzyloxy-4-
hydroxymethylcyclohexanes (by reaction with sodium
hydride and benzyl bromide)14 and subsequent tetrahy-
dropyranylation of the monoethers following a previously
described procedure.23
YH
+
+
+
H C
CHPh +H3C
CHPh +
CH2Ph +
2
YH
(30 %)
b
(35 %)
CH3
(35 %)
c
a
Scheme 1
1-Benzyloxymethyl-4-˛-phenylethylcyclohexane
(5)
In view of the above results, it was of interest to explore
whether the bond-forming intramolecular interactions, anal-
ogous to those occurring in benzyl diesters and diethers, also
take place if one or both benzyls are replaced by other
aryl groups or by non-aromatic moieties (Scheme 2). In
this paper, we present a study of the mass spectrometric
behavior of a series of difunctional oxygen derivatives bear-
ing benzyl, ˛- and ˇ-naphthylmethyl, 9-anthracylmethyl, ˛-
and ˇ-phenylethyl, allyl, propargyl, isopropyl, acetyl and
tetrahydropyranyl groups.
(mixture of cis- and trans-isomers) was obtained from
cis- and trans-1-benzyloxy-4-hydroxymethylcyclohexanes by
reaction with sodium hydride and ˛-phenylethyl bromide
(in THF) following a previously described procedure.14
To prepare 1-acetoxycarbonyl-4-benzyloxymethylcyclo-
hexane (7) (mixture of cis- and trans-isomers), 1-benzyloxy-
methyl-4-cyclohexanecarboxylic acid (cis and trans mixture)
was synthesized by partial etherification of a mixture of
cis- and trans-cyclohexane-1,4-dimethanols (by benzyl chlo-
ride and 50% aqueous sodium hydroxide solution)24 to
yield the corresponding benzyl monoether, and subse-
quent oxidation of the hydroxymethyl group with pyri-
dinium dichromate.25 Triethylamine (0.34 ml, 2.42 mmol)
was added dropwise to a cold (ice–water bath) mixture of cis-
and trans-1-benzyloxymethyl-4-cyclohexanecarboxylic acids
(0.3 g, 1.21 mmol) and acetyl chloride (0.14 g, 1.82 mmol) in
dry diethyl ether (8 ml). The reaction mixture was stirred at
room temperature overnight, filtered and washed with 5 ml
portions of diethyl ether. Concentration of the filtrate under
reduced pressure yielded 80% of the mixed anhydride 7.
Benzyl-9-anthracylmethyl adipate (10) was synthesized
from adipic acid dichloride by reaction with a 1 : 1 mix-
ture of benzyl and 9-anthracylmethyl alcohols and 4-
dimethylaminopyridine. To a stirred solution of adipic acid
dichloride (0.05 g, 0.27 mmol) in dichloromethane (1 ml) at
YH
YH
Y
R
CI
CID
or
CI
[R' R - H]+
rearrangement ion d
+
MH+
R'
Y
Y = -COO-; -O-
R, R'=Benzyl, Naphthylmethyl,
9-Anthracylmethyl, Allyl, Propargyl,
Acetyl, 2-Propyl, Tetrahydropyranyl
Scheme 2
EXPERIMENTAL
Mass spectrometry
Gas chromatographic and direct exposure probe chemi-
cal ionization mass spectrometric analyses (GC/CI-MS and
DEP/CI-MS) and CID measurements were carried out on a
Finnigan TSQ-70B triple-stage quadrupole mass spectrome-
ter. The stereoisomeric pairs 1–6 were introduced as mixtures
and separated on a DB-5 capillary column (30 m ð 0.25 mm
i.d., 0.25 µm film thickness, temperature programmed from
°
0 C under an N2 atmosphere was added a solution of
DMAP (0.08 g, 0.68 mmol) in CH2Cl2 (1 ml), followed by
addition of a mixture of benzyl (0.04 g, 0.324 mmol) and
9-anthracylmethyl (0.07 g, 0.324 mmol) alcohols in the same
solvent (2 ml). After stirring for 24 h at room temperature,
water (4 ml) was added and the dichloromethane layer was
washed with 10% hydrochloric acid and 5% NaHCO3. The
60 to 280 C at 15 C minꢀ1). The scan rate was 1 scan sꢀ1. The
°
°
cis-isomers were first and followed by the trans-counterparts
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

Electrophilic aromatic substitution in arylmethyl-containing difunctional compounds 1171
organic phase was dried over MgSO4 and evaporated under
The rearrangement leading to the formation of ion
d5 from 5 is highly stereospecific, affording an abundant
ion (relative abundance (RA) 66%) in the isobutane-CI
mass spectrum of trans-5, but a very low one (RA 1%)
in the cis-isomer. The low abundance of ion d5 in the
mass spectrum of cis-5 presumably results from the high
efficiency of the competing elimination of styrene, which
affords the most abundant m/z 235 fragment ion. The high
efficiency of this competing dissociation may result from
stabilization of the [MH ꢀ styrene]C ion by the internal
hydrogen bond between the two oxygen functions, which
is possible only in the cis-isomer. A detailed study of a
similar stereospecific behavior has been reported recently
for tetrahydropyranyl (THP) ethers of cis- and trans-1-
alkoxymethyl-4-cyclohexylmethanols and for THP esters of
cis- and trans-1,3-cyclohexanedicarboxylic acids.23
vacuum. The diester 10 was obtained in 83% yield after
purification on a silica gel column (hexane–ethyl acetate
(3 : 1)). Adipic acid dichloride was obtained by reaction
of adipic acid with thionyl chloride, following a reported
procedure.26 9-Anthracylmethyl alcohol was prepared by
formylation of anthracene with dimethylformamide in the
presence of phosphorus oxychloride (Vilsmeier reaction)27
and subsequent reduction of the resulting 9-anthraldehyde
with sodium borohydride.28
Di-9-anthracylmethyl adipate (11) was prepared from
adipic acid dichloride and 9-anthracylmethyl alcohol in the
same manner as 10.
RESULTS AND DISCUSSION
Mixed derivatives of dicarboxylic acids, diols and acid
alcohols 1–10 were prepared for this study. The isobutane-CI
mass spectral data for these compounds are given in Table 1
and the CID spectra of their MHC ions are given in Table 2.
Propargyl, allyl and 9-anthracylmethyl derivatives
The data in Tables 1 and 2 show that the benzyl group
of the MHC ions of 1, 2 and 10 interacts also with
the propargyl, allyl and 9-anthracylmethyl moieties to
give rise to new C—C bonds. However, in these cases
the abundances of the rearrangement ions d are much
lower than those of the protonated molecules of trans-
5, 6, 8 and 9. The extents of the rearrangement for the
stereoisomeric benzylisopropyl diesters 3 and the ben-
zyloxy anhydrides 7 are even smaller, and the rear-
rangement ions d are entirely absent in the CI and
CID mass spectra of cis- and trans-1-benzyloxymethyl-4-
tetrahydropyranoxymethylcyclohexanes 4.
O
COOCH2C CH
COOCH(CH3)2
COOCH2CH CH2
CH O
2
COOCH2Ph
1 (cis; trans)
COOCH2Ph
3 (cis; trans)
COOCH2Ph
2 (cis; trans)
CH2OCH2Ph
4 (cis; trans)
CH2OCH(CH3)Ph
COOCOCH
3
COOCH CH Ph
2
2
The observed lower efficiencies of the intramolecular
benzyl–propargyl and benzyl–allyl interactions occurring
in the CI and CID fragmentation of diesters 1 and 2, respec-
tively, relative to those of the corresponding benzyl–benzyl
interactions,13–15,29 can be rationalized on the basis of the
following arguments. The hydride ion affinities of the propar-
gyl and allyl cations are considerably higher than that of
the benzyl cation (by 33 and 18 kcal molꢀ1, respectively30
ꢁ1 kcal D 4.184 kJꢂ). The hydride ion affinity scale is consid-
ered as a reliable convenient basis for the comparison of the
relative stabilities of carbocations.31 Consequently, the het-
erolysis of the O—R bonds of the protonated propargyloxy-
and allyloxycarbonyl groups, resulting in the formation of
propargyl and allyl cations, respectively, is expected to be
more endothermic than that of the O–benzyl bond. The pref-
erential heterolysis of the O–benzyl bonds in the MHC ions
of 1 and 2 presumably leads to the ion–neutral complexes
C1 and C2, respectively, as shown in Schemes 4 and 5. The
propensity of ethylene and acetylene for electrophilic sub-
stitution is known to be much lower than that of benzene.32
Therefore, the electrophilic substitution of the propargyl
and allyl groups by the benzyl cation in the ion–neutral
complexes C1 and C2, respectively, via the corresponding
intermediates D1 and D2 is expected to be slow, resulting in
relatively low abundance ions d1 and d2.
CH2OCH2Ph
5 (cis; trans)
CH2OCH2Ph
7 (cis; trans)
COOCH2Ph
6 (cis; trans)
CO2CH2
CO2CH2
(CH2)4
(CH2)4
CO2CH2
(CH2)4
CO2CH2
CO2CH2
10
CO2CH2
9
8
Phenylethyl and naphthylmethyl derivatives
The results of the CI and CID measurements reveal that the
MHC ions of trans-5, 6, 8 and 9 containing ˛- or ˇ-phenylethyl
and ˛- or ˇ-naphthylmethyl groups, respectively, undergo
an efficient rearrangement leading to the formation of
benzyl–R covalent bonds (ions d5, d6, d8 and d9 in Scheme 3),
in analogy with the generation of the [C14H13]C (m/z
181) ion in the fragmentation of the protonated dibenzyl
derivatives.13–15 Plausible structures of the abundant ions
d5, d6, d8 and d9 are proposed in Scheme 3.
The results of the CID measurements of the m/z 195 ions
d5 and d6, summarized in Table 3, show significant difference
in the formation of the m/z 167 production, which is present
(at relatively low abundance) in the spectrum of ion d6, but
absent in that of d5. The presence of this [parent ꢀ C2H4]C
ion is consistent with the ethyldiphenylmethyl structure
proposed for ion d6 in Scheme 3. The preferential cleavage
of the O–benzyl bond on the way to the formation of
the ion–neutral complex C6, as compared with the O–ˇ-
phenethyl bond, is proposed to be the origin of the formation
of the m/z 195 ion d6 from the MHC ion of 6.
Isopropyl and tetrahydropyranyl derivatives
The reluctance of cis- and trans-1-benzyloxycarbonyl-4-
isopropoxycarbonylcyclohexanes 3 to undergo a similar rear-
rangement (very low abundance m/z 133 ion, see Tables 1
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

1172
M. Edelson-Averbukh and A. Mandelbaum
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

Electrophilic aromatic substitution in arylmethyl-containing difunctional compounds 1173
Table 2. CIDa mass spectral datab,c of MHC ions obtained from 1–3 trans-4 and 6–9 on isobutane-CI
Ion
Compound
R
Ion d [C7H7] m/z 91 [MH ꢀ BnOH]C [MH ꢀ ROH]C [MH ꢀ BnOR]C Other fragments
cis-1
Propargyl
22
25
14
30
29
33
63
45
2
4
<0.1
5
12
m/z 109 (3%): m/z 127
(7%): m/z 147 (22%)
m/z 109 (4%): m/z 127
(18%): m/z 147 (9%)
m/z 109 (1%): m/z 127
(1%)
trans-1
cis-2
Propargyl
Allyl
1
6
8
8
trans-2
Allyl
<0.1
2
2
m/z 41 (2%): m/z 109
(1%): m/z 127 (3%):
m/z 171 (4%): m/z 199
(7%): m/z 217 (4%)
m/z 263
cis-3
Isopropyl
Isopropyl
0.4
56
39
14
8
<0.1
6
14
2
1
1
[MH ꢀ propene]C
(21%)
trans-3
trans-4
0.5
m/z 263
[MH ꢀ propene]C
(57%)
Tetrahydropyranyl <0.1
<0.1
<0.1
m/z 85 [C5H7O]C
(41%): m/z 109 (8%):
m/z 125 (5%): m/z 213
(15%): m/z 235
[MH ꢀ DHP]C (8%)
m/z 105 [C8H9]C
(1%): m/z 349
cis-6
ˇ-Phenylethyl
ˇ-Phenylethyl
46
52
18
3
2
0.6
[MH ꢀ H2O]C (30%)
m/z 105 [C8H9]C (45%)
m/z 139 (2%): m/z 199
[MH ꢀ C7H8]C (2%):
m/z 249
trans-6
7 (cis: trans)d Acetyl
3
62
<0.1
0.6
<0.1
3
<0.1
2
0.4
[MH ꢀ CH2CO]C
(28%)
8
9
˛-Naphthylmethyl 29
ˇ-Naphthylmethyl 41
<0.1
<0.1
<0.1
<0.1
<0.1
m/z 141 [C11H9]C
(67%): m/z 359
[MH ꢀ H2O]C (4%)
m/z 141 [C11H9]C
(56%): m/z 157 (2%)
0.2
0.4
0.4
a 30 eV collision energy.
b The CID spectra of the MHC ions of cis-4, cis-5, trans-5 and 10 were not measured because of the low abundances of the MHC ions in
the isobutane-CI mass spectra.
c The ion abundances are listed as percentages of the total product ion current ꢁ%ꢂ.
d The data are given for a mixture of the cis- and trans-epimers.
and 2) is obvious. Similarly to the propargyl and allyl deriva-
tives 1 and 2, the rupture of the O–benzyl bond in diesters
3, resulting in the formation of the benzyl cation, is favored
over that leading to the isopropyl cation31 (the hydride ion
affinity of the isopropyl cation ꢁDꢁs-C3H7C ꢀ Hꢀꢂꢂ is higher
be attracted by the benzyl cation in the ion–neutral com-
plex C3.
The high abundance of the m/z 85 tetrahydropyranyl
(THP) ion and the very low abundance of the benzyl ion
in the CI and CID spectra of the stereoisomeric benzyl
tetrahydropyranyl ethers 4 suggest preferential cleavage
of the THP–O bond, possibly leading to the ion/neutral
complex C4. The absence of the m/z 175 rearrangement ion
in the CI and CID spectra of the diethers 4 suggests non-
occurrence of an electrophilic attack of the THPC ion at
the phenyl ring of the benzyloxy group. Such attack would
result in the formation of intermediate D4 (see Scheme 6),
that would be destabilized as compared with the ion–neutral
C
than that of the benzyl carbocation ꢁDꢁPhCH2 ꢀ Hꢀꢂꢂ by
14 kcal molꢀ1 (Ref. 30)). The m/z 43 isopropyl ion is indeed
absent in the CID spectra of the MHC ions of cis-3 and
trans-3 (it is below the mass range of isobutane-CI mea-
surements). The m/z 91 cation is relatively abundant in the
CI mass spectra of cis-3 and trans-3, and even more in the
CID spectra of their MHC ions (see Tables 1 and 2). How-
ever, there are no ꢃ-electrons in the isopropoxy moiety to
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

1174
M. Edelson-Averbukh and A. Mandelbaum
Table 3. CIDa mass spectral datab of ions d5 and d6
(m/z 195), obtained from 5 and 6 on isobutane-CI
CH2OCH2Ph
CH3
+
+
CI
+
CH3
CH3CHPh
MH
5
Compound
ion d5
and/or isomer(s)
m/z 195
CH2OH
ion/neutral
complex C5
Ion
cis-5
trans-5
cis-6
trans-6
m/z 180
m/z 167
m/z 117
m/z 103
m/z 91
<0.1
<0.1
38
<0.1
62
<0.1
<0.1
16
<0.1
84
3
3
21
2
3
3
22
2
COOCH2CH2Ph
+
+
CI
CH2Ph
+
MH
CH2CH3
6
ion d6
and/or isomer(s)
m/z 195
COOH
ion/neutral
complex C6
71
70
a 40 eV collision energy.
b The ion abundances are listed as percentages of the
total product ion current (%).
CH3
+
CO2H
+H2C
CI
+
8
MH
(CH2)4
CO2CH2
abundant [MH ꢀ CH3COOH]C ion in the CI mass spectrum
of 7 shows the elimination of acetic acid is the most efficient
fragmentation involving the acetyl group.
ion d8
and/or isomer(s)
m/z 231
ion/neutral
complex C8
+
+
CO2H
(CH2)4
9-Anthracylmethyl derivatives — steric hindrance
The m/z 191 9-anthracylmethyl cation is highly abundant in
the isobutane-CI mass spectrum of benzyl-9-anthracylmethyl
adipate (10), while the [C7H7]C ion is absent. In this
respect the behavior of 10 resembles that of the ˛-and ˇ-
naphthylmethyl analogues 8 and 9. However, unlike 8 and 9,
10 undergoes inefficient rearrangement giving rise to a low-
abundance (4%) m/z 281 ion d10 (see Table 1). This different
behavior of the naphthylmethyl and 9-anthracylmethyl
derivatives is attributed to a steric factor. Unlike the ˛-
and ˇ-naphthylmethyl ions, the methylene group of the
9-anthracylmethyl cation is hindered from both sides by
the 1-H and 8-H atoms of the anthracene ring, resulting in
a higher energy barrier for the electrophilic attack at the
phenyl ring of the benzyloxy group (Scheme 8).
The isobutane-CI and CID data listed in Tables 1 and
2 show that the abundance of the rearrangement ion
d9 obtained from the protonated molecule of benzyl-ˇ-
naphthylmethyl adipate (9) is significantly higher than that
of the isomeric benzyl-˛-naphthylmethyl dicarboxylate (8).
This behavior is in agreement with the steric hindrance at
the methylene carbon of the ˛-naphthylmethyl cation by the
CI
+
H2C
MH
9
CH3
CO2CH2
ion d9
and/or isomer(s)
m/z 231
ion/neutral
complex C9
Scheme 3
complex C4 (benzenium ion in D4 instead of the phenyl
group in C4, and tetrahydropyranyl moiety in D4 instead
of the THP cation in C4). Steric hindrance may also have an
effect in the reluctance of the ion–neutral complex C4 to form
intermediate D4.
Acetyl derivative
The very high abundance of the [C7H7]C ion in the CI
mass spectrum of the benzyloxy anhydride 7 (cis- and trans-
isomer mixture) and in the CID spectrum of the MHC ion
(Tables 1 and 2), and the absence of the acetyl cation in the
CID spectrum (it could not be measured upon CI), indicate
preferential cleavage of the O–benzyl bond. This behavior
explains the very low efficiency of the rearrangement leading
to the low-abundance m/z 133 ion d7 (Scheme 7). The highly
OH
OH
OH
C
O
O
C
O
C
MH+ of
trans-1
+
CH2
and/or
H
C+
C
C+
CH2
H
CH2
H
O
O
C
H
C
O
C
O
OCH2C
CH
C
O
CHPh
CHPh
ion/neutral
complex C1
Intermediate D1
+
CH CH C CH2
COOH
COOH
+
ion d1
or isomer thereof
Scheme 4
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

Electrophilic aromatic substitution in arylmethyl-containing difunctional compounds 1175
OH
C
OH
C
OH
C
O
O
O
MH+ of
trans-2
+
H
C
H
C+
CH2
and/or
+
CH2
H
CH2
H
O
O
OCH2CH CH2
C
O
C
O
C
O
CH
CH2Ph
CH
CH2Ph
ion/neutral
complex C2
Intermediate D2
+
CH CH2
CH
COOH
CH2
+
ion d2
or isomer thereof
COOH
Scheme 5
Table 4. Isobutane-CIa and CIDb (of MHC ions) mass spectral
data for dianthracylmethyl and dinaphthylmethyl adipates
(11–13)
CH2 OCH2Ph
H
OCH2Ph
CH2
+
OCH2
CH2
O
+
O
H
O
CH2
O
+
Isobutane-CI
(relative abundance, %)
CH2OH
CH2OH
Intermediate D4
CID (%)c
ion/neutral
complex C4
MH+ of 4
Compound
MHC
Ion d
Ion d
Scheme 6
i
11d
12e,f
13g,h
<0.1
5
13
<0.1
100
100
65
85
CH3CO+
efficient
efficient
[MH-CH3COOH]+
a Ranges of the CI measurements: m/z 220–600 (11); m/z 170–500
(12 and 13).
MH+ of 7
+
PhCH2
b 30 eV collision energy.
+
CH2
c The CID data are listed as percentages of the total product ion
current ꢁ%ꢂ.
d Relative abundances of additional fragments in the isobutane-
CI mass spectrum: m/z 233 (37%); m/z 247 (86%); m/z 336
(100%); m/z 351 (11%); m/z 369 (13%); m/z 382 (26%); m/z
383 (20%).
e Relative abundance of an additional fragment in the isobutane-
CI mass spectrum: m/z 183 (6%).
f Additional fragments in the CID spectrum: m/z 141 [C11H9]C
(12%); m/z 157 (11%); m/z 285 (5%); m/z 286 (7%).
g Relative abundance of additional fragment in the isobutane-CI
mass spectrum: m/z 183 (3%).
h Additional fragments in the CID spectrum: m/z 141 [C11H9]C
(6%); m/z 157 (7%); m/z 285 (1%); m/z 286 (1%).
i The CID spectrum was not measured because of the low
abundance of the MHC ion in the isobutane CI mass spectrum.
inefficient
COCH3
ion d7
Scheme 7
CH3
H
+H2C
H
CO2H
(CH2)4
CO2CH2
+
CI
10
MH+
inefficient
ion/neutral
complex C10
ion d10
and/or isomer(s)
Scheme 8
8-H atom of the naphthalene ring of the carbocation, which
is absent in the corresponding ˇ-isomer.
and 2). The different CID spectra (50 eV collision energy) of
ions d12 and d13 (m/z 266 and 265 in both, but an m/z 252
[parent ꢀ C2H4]C ion only in that of d12) indicate different
structures for these two ions.
The effect of steric hindrance at the 9-anthracylmethyl
position is demonstrated in the behavior of di-9-anthracyl-
methyl adipate (11) under isobutane-CI conditions (the CID
spectrum could not be measured because of the absence of
the MHC ion). The m/z 191 anthracylmethyl cation is the
most abundant ion in the mass spectrum, and the m/z 381
rearrangement ion d11 is absent (see Table 4 and Scheme 9).
In contrast, the m/z 281 rearrangement ions d12 and d13
are the most abundant products in the isobutane-CI and CID
spectra of ˛- and ˇ-naphthylmethyl adipates 12 and 13 (Figs 1
CONCLUSION
We have shown that the previously reported rearrangement
of a variety of gas-phase protonated dibenzyl derivatives,
resulting in abundant [C14H13]C (m/z 181) cations, takes
place also when one or both benzyls are replaced by other
Copyright  2003 John Wiley & Sons, Ltd.
J. Mass Spectrom. 2003; 38: 1169–1177

1176
M. Edelson-Averbukh and A. Mandelbaum
CI
CH OCO(CH ) COOCH
2
ion d11 (m/z 381)
2
2 4
11
CI
and
CID
CH3
+
CH
CH OCO(CH ) COOCH
2 4
2
2
ion d12 (m/z 281)
and/or isomer(s)
12
CI
and
CID
CH OCO(CH ) COOCH
2 4
+
CH
2
2
H3C
13
ion d13 (m/z 281)
and/or isomer(s)
Scheme 9
Figure 2. CID mass spectra (30 eV collision energy) of the
MHC ions obtained on isobutane-CI from (a) 12 and (b) 13.
electrophilicity of the RC ions. The low efficiency of this rear-
rangement in 9-anthracylmethyl derivatives, in contrast to
˛- and ˇ-naphthylmethyl analogs, indicates high sensitivity
of this unique process to steric hindrance.
Acknowledgements
This work was supported by the Fund for Promotion of Research
at the Technion. We are grateful to Mr A. Etinger for techni-
cal assistance.
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