Collision-induced dissociation study of stereospecific elimination processes of stereoisomeric phenylcyclohexanols and their derivatives upon electron ionization

Article abstract of DOI:10.1002/(SICI)1096-9888(199809)33:9<819::AID-JMS690>3.0.CO;2-7

The electron ionization (EI)-induced elimination of water, methanol and acetic acid from the M^+. ions of stereoisomeric 2-, 3- and 4-phenylcyclohexanols and their methyl ethers and acetates, respectively, was studied by deuteration and collision-induced dissociation (CID) techniques. The highly stereospecific elimination processes in trans-3- and -4-phenylcyclohexanols and in the corresponding methyl ethers and acetates take place with the involvement of the benzylic hydrogen atom, suggesting syn-1,3- and syn-1,4-elimination via cyclic transition states. The elimination processes from the cis-alcohols and their methyl ethers occur mainly after ring opening, and result in the formation of mixtures of product ions. The elimination processes are non-stereospecific in the stereoisomeric 2-phenyl-substituted systems, and are preceded by ring cleavage in both cis- and trans-isomers, resulting in mixtures of cyclic and acyclic product ions. All cis-2-, -3- and -4-phenylcyclohexyl acetates undergo elimination by a McLafferty-type mechanism with the abstraction of a hydrogen atom from positions 2 and/or 6. An interesting outcome of this work is that the majority of the gas-phase isomeric hydrocarbon phenyl-C₆H₉ radical cations, formed either by EI-induced fragmentation of stereoisomeric phenylcyclohexyl derivatives or by EI of a variety of phenyl-C₆H₉ isomers, retain their structural integrities. On the other hand, the CID spectra of the even-electron phenyl-C₆H₁₀⁺ ions produced by chemical ionization (CI)-induced fragmentation from isomeric phenylcyclohexanols and their methyl ethers and acetates are similar, indicating loss of structural information under CI in this system.

Full text of DOI:10.1002/(SICI)1096-9888(199809)33:9<819::AID-JMS690>3.0.CO;2-7

JOURNAL OF MASS SPECTROMETRY
J. Mass Spectrom. 33, 819È835 (1998)
Collision-induced Dissociation Study of
StereospeciÐc Elimination Processes of
Stereoisomeric Phenylcyclohexanols and Their
Derivatives Upon Electron Ionization
N. Khaselev and A. Mandelbaum*
Department of Chemistry, TechnionÈIsrael Institute of Technology, Haifa, Israel
The electron ionization (EI)-induced elimination of water, methanol and acetic acid from the M‘~ ions of stereoiso-
meric 2-, 3- and 4-phenylcyclohexanols and their methyl ethers and acetates, respectively, was studied by deuter-
ation and collision-induced dissociation (CID) techniques. The highly stereospeciÐc elimination processes in
trans-3- and -4-phenylcyclohexanols and in the corresponding methyl ethers and acetates take place with the
involvement of the benzylic hydrogen atom, suggesting syn-1,3- and syn-1,4-elimination via cyclic transition states.
The elimination processes from the cis-alcohols and their methyl ethers occur mainly after ring opening, and result
in the formation of mixtures of product ions. The elimination processes are non-stereospeciÐc in the stereoisomeric
2-phenyl-substituted systems, and are preceded by ring cleavage in both cis- and trans-isomers, resulting in mix-
tures of cyclic and acyclic product ions. All cis-2-, -3- and -4-phenylcyclohexyl acetates undergo elimination by a
McLa†erty-type mechanism with the abstraction of a hydrogen atom from positions 2 and/or 6. An interesting
outcome of this work is that the majority of the gas-phase isomeric hydrocarbon phenyl-C H radical cations,
6
9
formed either by EI-induced fragmentation of stereoisomeric phenylcyclohexyl derivatives or by EI of a variety of
phenyl-C H isomers, retain their structural integrities. On the other hand, the CID spectra of the even-electron
6
9
phenyl-C H‘ ions produced by chemical ionization (CI)-induced fragmentation from isomeric phenylcyclohexa-
6
10
nols and their methyl ethers and acetates are similar, indicating loss of structural information under CI in this
system. ( 1998 John Wiley & Sons, Ltd.
KEYWORDS: stereochemical e†ects; electron ionization; chemical ionization; collision-induced dissociation; deuterium
labelling; phenylcycloalkanols; ethers; acetates
suggests the mechanism shown in Scheme 2 for the EI-
induced dehydration of trans-arylcyclohexanols 2t and
3t.
INTRODUCTION
Similar behavior has been observed for the elimi-
nation of methanol from the analogous 3- and 4-
arylcyclohexyl methyl ethers 5 and 6 (the 2-aryl-
substituted analogs 4 have not been reported): a highly
stereo- and regiospeciÐc efficient elimination of meth-
anol from the trans-ethers involving the benzylic hydro-
gen atoms, in contrast to the cis-isomers, which a†ord
low abundance [M [ MeOH]`~ ions (although with
signiÐcant abstraction of hydrogens from the benzylic
position).8 trans-3- and 4-aryl acetates 8 and 9 (the
2-aryl-substituted acetates 7 have not been reported)
also exhibit a similar highly stereo- and regiospeciÐc
elimination of acetic acid involving the benzylic posi-
tion, while the cis-isomers undergo a 1,2-elimination.9
Deuterium labeling studies provide preliminary infor-
mation on the mechanistic pathways of the elimination
processes, but not necessarily on the structures of the
resulting fragment ions. An extensive collision-induced
dissociation (CID) study has been undertaken in order
to solve the ion structure problem, and consequently to
obtain a better understanding of the above elimination
The stereochemistry of elimination processes of gas-
phase ionized alcohols, ethers and esters has been of
considerable interest since the early times of organic
mass spectrometry.1h6 The elimination of H O from 3-
2
and 4-arylcyclohexanols 2t and 3t under electron ion-
ization (EI) is a highly stereospeciÐc process (the isom-
eric 2-arylcyclohexanols 1c and 1t were not reported).7
Highly abundant [M [ H O]`~ ions are formed from
2
the trans-isomers 2t and 3t while the cis-analogs 2c and
3c a†ord relatively low abundance dehydration product
ions (Scheme 1).
Deuterium labeling studies have shown that the H O
2
elimination process involves the benzylic hydrogens
with high speciÐcity in the trans-alcohols.7 This Ðnding
* Correspondence to: A. Mandelbaum, Department of Chemistry,
TechnionÈIsrael Institute of Technology, Haifa, Israel.
E-mail: chr17am=tx.technion.ac.il
Contract/grant sponsor: Fund for Promotion of Work at the Tech-
nion.
CCC 1076È5174/98/090819È17 $17.50
( 1998 John Wiley & Sons, Ltd.
Received 13 March 1998
Accepted 19 May 1998

820
N. KHASELEV AND A. MANDELBAUM
Scheme 1.
processes of stereoisomeric phenylcyclohexanols and
their derivatives upon EI.
Table 1. Relative abundances (%) of M‘~and [M Ô H O]‘~
2
ions in the EI mass spectra of stereoisomeric 2-, 3-
and 4-phenylcyclohexanols
ÍM˽~
ÍM ÉH O˽~
ÍM ÉH O˽~/ÍM˽~
trans/cisa
RESULTS AND DISCUSSION
2
2
1c
1t
2c
2t
3c
3t
100
100
100
8
19.4
20.9
25
0.2
0.2
1.0
50
The results of the present EI mass spectral measure-
ments of the cisÈtrans pairs of 2-, 3- and 4-
phenylcyclohexanols and their methyl ethers and
acetates are listed in Tables 1È3. The pronounced di†er-
ence in the fragmentation behavior of the cis- and trans-
isomers, previously reported for the 3- and 4-phenyl
series, has been reproduced in the present measure-
ments. In contrast to the stereospeciÐc nature of the
fragmentation of the latter pairs of stereoisomers, cis-
and trans-2-phenylcyclohexanols 1c and 1t and their
derivatives 4c, 4t, 7c and 7t exhibit non-stereospeciÐc
0.25
12.5
0.2
100
20
100
3.4
100
29
145
a The ion abundance ratio (ÍM ÉH O˽~/ÍM˽~)
ÉH O˽~/ÍM˽~) is considered as the degree of stereospecifi-
city in the fragmentation of stereoisomers.
/(ÍM
2
trans
2
cis
phenylcyclohexanols and their methyl ethers and
acetates, was performed in order to determine the struc-
tures of these elimination ions. This study showed that
the problem is involved, and consequently the relatively
large set of isomeric m/z 158 standard precursors 10È31
shown in Scheme 3 was prepared. The low-energy CID
spectra of the m/z 158 radical cations, obtained upon EI
from these materials, are shown in Figs 1È9.
elimination of H O, MeOH and AcOH, respectively,
2
a†ording comparable abundances of the m/z 158 [M
[ ROH]`~ ions.
A preliminary CID study of the structures of the [M
[ ROH]`~ ions obtained upon EI from 1È9, using a
small number of standards, which are possible products
of elimination of H O, MeOH and AcOH from
2
Table 2. Relative abundances (%) of M‘~ and [M
Ô CH OH]‘~ ions in the EI mass spectra of stereo-
3
isomeric 2-, 3- and 4-phenylcyclohexyl methyl ethers
ÍM˽~
ÍM ÉCH OH˽~
ÍM ÉCH OH˽~/ÍM˽~
trans/cis
3
3
4c
4t
5c
5t
6c
6t
100
100
100
Ä0.5
100
6.8
40
40
0.5
0.3
1
¿500
50
35
0.4
100
26.4
100
¿200
0.3
15
Scheme 2.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
821
parison of the CID spectra of these m/z 158 ions with
that obtained by EI of 2-phenyl-1,5-hexadiene (20) (see
Figs 4 and 7) also show a high degree of similarity
Table 3. Relative abundances (%) of M‘~ and [M
Ô AcOH]‘~ ions in the EI mass spectra of ste-
reoisomeric 2-, 3- and 4-phenylcyclohexyl ace-
tates
(r
\ 0.9895,
r
\ 0.9970,
r
\ 0.9973).
10ah20
10bh20
10ch20
These results lead to the conclusion that the m/z 158
ions obtained from 10a, 10b, 10c and 20 may have iden-
tical structures (Scheme 4). Ring opening of the aryl-
and alkyl-substituted cyclohexane-1,4-diyl cation rad-
icals has been demonstrated previously in the con-
densed phase.11 On the other hand, the results of the
CID measurements show that these ions do not isomer-
ize to phenylcyclohexene structures 17, 18 and 19 by
ÍM˽~
ÍM ÉAcOH˽~
ÍM ÉAcOH˽~/ÍM˽~
trans/cis
7c
7t
8c
8t
9c
9t
Ä0.5
Ä0.5
20
100
100
100
100
40
¿200
¿200
5
¿1
¿30
¿2.5
Ä0.5
Ä0.5
Ä0.5
¿200
¿80
¿200
100
hydrogen migrations (r
\ 0.5543,
r
\
10ah17
10bh18
0.5650, r
\ 0.0149; see Figs 4 and 6), in contrast
10ch19
CID standards
to the data reported on the chemistry of cyclohexane-1,
4-diyl radical cation in solution,12,13 or to methyl
We were not successful in our attempts to synthesize
1-phenylbicyclo[2.2.0]hexane (32), which is the most
probable intermediate of the product of elimination of
phenylcyclopentenes 12È16 (r
\ 0.0201; r
\
\
10ah12
10bh13
10bh16
0.0190, r
\ 0.0280, r
\ 0.0305, r
10ch14
10ah15
0.0289; see Figs 4 and 5), by a skeletal rearrangement,
which might be involved in the elimination processes,
by analogy to the ion chemistry of cyclohexyl deriv-
atives.14h16 The above information on the isomer-
H O, MeOH and AcOH from trans-4-phenylcyclohexa-
2
nol (3t) and its methyl ether (6t) and acetate (9t).10 Stan-
dard materials 10a, 10b and 10c were used as potential
precursors of ionized 32. As expected, the m/z 158 ions,
obtained by decarboxylation of the two lactones 10b
ization and structure retention behavior of the C H`~
12 14
radical cations is summarized in Scheme 4.
and 10c and by the loss of N from 10a under EI condi-
The isomeric ionized phenylcyclohexenes 17, 18 and
19 may be formed by a 1,2-elimination of acetic acid
from phenylcyclohexyl acetates 7, 8 and 9. The isomeric
2
tions, exhibit very similar CID spectra (correlation
coefÐcients r
\ 0.9978, r
\ 0.9878). Com-
10bh10c
10ah10b
Scheme 3.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

822
N. KHASELEV AND A. MANDELBAUM
Figure 1. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158
ÍM ÉROHË½Õ ions, obtained upon EI from stereoisomeric 2-phenylcyclohexanols and their methyl ethers and acetates: (a) 1c; (b) 1t; (c)
4c; (d) 4t; (e) 7c; (f) 7t.
1- and 3-phenylcyclohexenes 17 and 18 exhibit similar
CID spectra (r \ 0.9849), which are entirely di†er-
structural features of isomeric ions, which may undergo
similar fragmentations.
17h18
ent from that of 4-phenylcyclohexene 19 (r
\
1,4-Elimination of H O and MeOH from cis-1,2- and
17h19
2
0.0250; see Fig. 6). The most abundant m/z 104 ion in
the CID spectrum of 19 corresponds to ionized styrene,
which is obtained by a retro-DielsÈAlder fragmentation
from this particular isomer. These Ðndings suggest pos-
sible isomerization of ionized 18 to the more stable
ionized 17, in contrast to the retention of structure of
the molecular ion of 19 (Scheme 5). It should be noted
that similar CID spectra do not exclude retention of
1,3-phenylcyclohexanols 1c and 2c and from their
methyl ethers 4c and 5c may result (at least in part) in
ionized 2-phenylbicyclo[2.2.0]hexane (34). We were not
successful in our attempts to synthesize this standard
compound. Therefore, diazine 11a and lactone 11b were
used as precursors of [34]`~. The m/z 158 ions,
obtained by loss of N from 11a and by decarboxyl-
2
ation of 11b under EI conditions, exhibit identical CID
Figure 2. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 ÍM
ÉROH˽~ ions, obtained upon EI from stereoisomeric 3-phenylcyclohexanols and their methyl ethers and acetates: (a) 2c; (b) 2t; (c) 5c;
(d) 5t; (e) 8c; (f) 8t.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
823
Figure 3. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 ÍM
ÉROH˽~ ions, obtained upon EI from stereoisomeric 4-phenylcyclohexanols and their methyl ethers and acetates: (a) 3c; (b) 3t; (c) 6c;
(d) 6t; (e) 9c; (f) 9t.
spectra (r
11ah11b
similar to those of 17 and 18 (r
11ah17
\ 0.9876). These CID spectra are
ionized 1-phenylbicyclo[3.1.0]hexane (28) to the 1-
phenylcyclohexene structure 17 by opening of the cyclo-
propane ring followed by hydrogen transfer (Scheme 5).
Isomerization of cyclopropane radical cations by ring
opening has been observed and discussed long time
ago.17 It is interesting to note here that, in contrast to
28, the di†erent CID spectra of 29 and of the stereoiso-
meric syn- and anti-bicyclo[3.1.0]hexane pairs 27 and
30 indicate retention of the original structures in their
radical cations.
\ 0.9878,
r
\ 0.9810), suggesting possible isomerization of
11ah18
[34]`~ or its corresponding 2-phenylcyclohexane-1,4-
diyl cation radical to [17]`~ (see Scheme 5).
The phenylbicyclo[3.1.0]hexane CID standards
27È30 were prepared in order to examine various pos-
sible cis-1,3-elimination processes. The CID spectrum of
the m/z 158 molecular ion of 1-phenylbicyclo[3.1.0]
hexane (28) is also similar to the CID spectra of 1- and
3-phenylcyclohexenes 17 and 18 (r
\ 0.9891,
The above results suggest isomerization of the cation
radicals of 18 and of the strained bicyclic structures 28
17h28
\ 0.9915). This Ðnding indicates isomerization of
r
18h28
Figure 4. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 ÍM
ÉCO ˽~ and ÍM ÉN ˽~ ions, obtained upon EI from bicyclic lactones and azines: (a) 10b; (b) 10c; (c) 11b; (d) 10a; (e) 11a.
2
2
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

824
N. KHASELEV AND A. MANDELBAUM
Figure 5. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 M½~ ions,
obtained upon EI from isomeric substituted cyclopentenes: (a) 31; (b) 15; (c) 14; (d) 16; (e) 12; (f) 13.
and 34 to the monocyclic isomer 17 (Scheme 5) and that
of 32 to the acyclic isomer 20 (Scheme 4).
With the exception of the above species, the CID
spectra of the m/z 158 ions obtained from the examined
isomeric standards exhibit signiÐcantly di†erent features
(often in terms of relative ion abundances), which
permit clear structural distinctions. The isomerization
processes proposed in Schemes 4 and 5 show that struc-
Figure 6. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 M½~ ions,
obtained upon EI from isomeric phenylcyclohexenes: (a) 17; (b) 18; (c) 19.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
825
Figure 7. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 M½~ ions,
obtained upon EI from isomeric phenylhexadienes: (a) 21-E ; (b) 21-Z ; (c) 22-EE ; (d) 22-EZ ; (e) 23; (f) 20.
tural assignments of the m/z 158 ions, based on com-
(9t), show identical CID spectra (r
3th6t
\ 0.9987) and, consequently, the elimination
\ 0.9986,
parison of CID spectra, are not unlimited.
r
3th9t
product ions obtained from the alcohol, ether and
acetate appear to have the same structure. The common
structure of the elimination product ions indicates
similar mechanism for the three elimination processes.
The CID spectra of the above m/z 158 [M [ ROH]`~
ion formed from 3t, 6t and 9t exhibit great similarity to
those obtained from 10a, 10b and 10c (see Scheme 4;
trans-4-Phenylcyclohexanol and its methyl ether and
acetate
The m/z 158 [M [ H O]`~ ion, obtained from trans-4-
2
phenylcyclohexanol (3t), the [M [ MeOH]`~ ion from
compare Figs 3 and 4; r
\ 0.9989, r
\
3th10a
3th10b
\ 0.5653,
trans-4-phenylcyclohexyl methyl ether (6t) and the [M
[ AcOH]`~ ion from trans-4-phenylcyclohexyl acetate
0.9973, r
\ 0.9981), whereas they di†er consider-
3th17
3th10c
ably from those of other precursors (e.g. r
Figure 8. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 M½~ ions,
obtained upon EI from isomeric phenylhexadienes: (a) 24-E ; (b) 24-Z ; (c) 25-E ; (d) 25-Z ; (e) 26-Z ; (f) 26-E.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

826
N. KHASELEV AND A. MANDELBAUM
Figure 9. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 158 M½~ ions,
obtained upon EI from isomeric phenylbicycloÍ3.1.0Ëhexanes: (a) 27-syn ; (b) 27-anti ; (c) 28; (d) 29; (e) 30-syn ; (f) 30-anti.
r
\ 0.6433, r
\ 0.015). These CID results, sum-
3th19
trans-3-Phenylcyclohexanol and its methyl ether and
3th18
marized in Scheme 6, are in good agreement with the
results of the EI mass spectral measurements and of the
deuterium labeling studies (see Scheme 2).7,8
acetate
In analogy to trans-4-phenylcyclohexanol, the m/z 158
[M [ H O]`~ ion obtained from trans-3-phenylcyclo-
2
hexanol (2t), the [M [ MeOH]`~ ion from trans-3-
phenylcyclohexyl methyl ether (5t) and the [M
[ AcOH]`~ ion from trans-3-phenylcyclohexyl acetate
Scheme 6.
Scheme 4.
Scheme 5.
Scheme 7.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
827
Scheme 8.
(8t) also show almost identical CID spectra (r
2th5t
\
cis-4-Phenylcyclohexanol and its methyl ether
0.9985, r
2th8t
\ 0.9887). Consequently, the elimination
product ions obtained from alcohol, ether and acetate
appear to have a common structure, indicating the
occurrence of a similar mechanism for the three elimi-
nation processes.
The CID spectra of the above m/z 158 [M [ ROH]`
ions formed from 2t, 5t and 8t exhibit great similarity to
those of 17 and 28 (compare Fig. 2 with Figs 6 and 9;
Previous deuterium labeling studies have shown that
the elimination of H O from the M`~ ion of cis-4-
2
phenylcyclohexanol (3c) and of methanol from its
methyl ether (6c) involves the benzylic hydrogen atom
from position 1 to a relatively small extent (24È30%).7,8
This Ðnding is consistent with the large distance
between that H-atom and the oxygen in the cis-isomers,
which does not allow a 1,4-elimination involving the
bezylic position. The major origin of the hydrogen atom
abstracted in the course of this elimination has not been
established in that study.
r
\ 0.9886, r
\ 0.9976), whereas they consider-
2th17
2th28
ably di†er from those of other precursors. This conclu-
sion, summarized in Scheme 7, is fully consistent with
the results of the EI mass spectral measurements and of
the deuterium labeling studies (see Scheme 2).
Scheme 9.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

828
N. KHASELEV AND A. MANDELBAUM
It could be expected that in the absence of the 1,4-
elimination channel, a 1,3-elimination process involving
one of the hydrogen atoms from positions 3 or 5 will
occur. Competing elimination processes initiated by
ring cleavage are also possible in the cyclohexanol
system. More than one location is accessible in the
elimination of the ring-open species.
The computer-aided analysis of the CID spectral data
leads to the conclusion that the [M [ H O]`~ and [M
2
[ MeOH]`~ ions, obtained from 3c and 6c, respec-
tively, are indeed mixtures of three isomeric ions [22-
EZ]`~, [24-E]`~ and [27]`~, which are formed by
initial a- or c-cleavage, and, to a smaller extent, by a
1,3-elimination from the intact M`~ ions involving one
of the hydrogen atoms from the homoallylic positions 3
and 5 (see Scheme 8). The CID study indicates prefer-
ential a-cleavage for the cis-ether 6c (55%), in contrast
to the corresponding alcohol 3c, where the elimination
Scheme 10.
nation of H O is the predominant process taking place
in 2c (60%), in contrast to 5c, where the 1,4-elimination
2
of MeOH is of minor importance (only 11%). The CID
study indicates preferential a-cleavage for the cis-ether
5c a†ording three isomeric fragment ions (see Scheme
10), in contrast to the corresponding alcohol 2c, where
the elimination initiated by a-cleavage is insigniÐcant,
and no structure related to such a process has been sug-
gested by the CID data analysis (see Scheme 10). Here
again the preferential a-cleavage of the cis-ethers may
be ascribed to the lower energy of such bond cleavage
in ethers, as compared with the corresponding alco-
hols.18 Mechanistic pathways for three elimination pro-
cesses preceded by a-, b- and c-CÈC bond cleavages
are proposed in Scheme 11.
of H O is initiated to a similar extent by the a- and
2
c-cleavages (D40%). The preferential a-cleavage, pre-
ceding the elimination of methanol from the M`~ ions
of cis-ethers, has been previously deduced from the deu-
terium labeling study, and it has been ascribed to the
lower energy of a-cleavage of ethers as compared with
the corresponding alcohols.18,19
cis-3-Phenylcyclohexanol and its methyl ether
The comparative analysis of the CID measurements of
cis-3-phenylcyclohexanol (2c) and of its methyl ether
(5c) with a variety of standards leads to the conclusion
cis- and trans-2-phenylcyclohexanols and their methyl
that the [M [ H O]`~ and [M [ MeOH]`~ ions
2
ethers
obtained from 2c and 5c, respectively, are mixtures of
isomeric ions, which are formed by elimination pro-
cesses initiated by a-, b- or c-cleavage, and by a 1,4-
elimination from the intact M`~ ions involving one of
the hydrogen atoms from position 4. The di†erence
between the alcohol and the ether in this series is much
more pronounced than in the case of 3c and 6c. cis-3-
Phenylcyclohexanol (2c) gives rise to three [M
The results of the EI mass spectral measurements, listed
in Tables 1 and 2, show similar behavior for cis- and
trans-2-phenylcyclohexanols (1c and 1t) and for the cor-
responding stereoisomeric methyl ethers (4c and 4t).
This behavior suggests similar mechanistic pathways for
each of the two stereoisomeric pairs.
[ H O]`~ ions shown in Scheme 9, while Ðve isomeric
The CID spectra of the m/z 158 ions obtained from
2
[M [ MeOH]`~ ions, shown in Scheme 10, are formed
the stereoisomeric alcohols 1c and 1t are similar
from the corresponding methyl ether 5c. The 1,4-elimi-
(r
1ch1t
\ 0.9700). The [M [ MeOH]`~ ions obtained
Scheme 11.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
829
Scheme 12.
from the corresponding methyl ethers 4c and 4t also
give rise to similar CID spectra (r \ 0.9789). More-
additional minor bicyclic fragment ion, 30-syn (6È7%),
by a 1,3-elimination process from the intact M`~ ions
involving the homobenzylic hydrogen atom from posi-
tion 3 (see Scheme 12). The axial conformation of the
hydroxy and methoxy groups in the cis-alcohol and
ether, respectively, may explain the formation of this
fourth product ion from 1c and 4c under EI conditions.
4ch4t
over, identity has been found in the CID spectra of the
[M [ H O]`~ and [M [ MeOH]`~ ions (r
\
2
1ch4c
0.9880, r
\ 0.9989). Consequently, the elimination
1th4t
product ions obtained from the stereoisomeric alcohols
and ethers appear to have similar structures, indicating
similar mechanisms for the elimination processes of
these precursors.
The comparative analysis of the CID measurements
of trans-2-phenylcyclohexanol 1t and of its methyl ether
4t with a variety of standards leads to the conclusion
2-, 3- and 4-phenylcyclohexyl acetates
It has been shown before that the mechanisms of the
EI-induced elimination of acetic acid from trans-3- and
-4-phenylcyclohexyl acetate (8t and 9t) are similar to
those of the corresponding trans-alcohols and methyl
ethers (2t and 5t and 3t and 6t) (Schemes 6 and 7). The
deuterium labeling study demonstrated major
abstraction of a hydrogen atom from the benzylic posi-
tion, which is accessible in the trans-isomers, and the
analysis of the present results of CID measurements
indicate identical structures of the [M [ AcOH]`~, [M
that the m/z 158 [M [ H O]`~ and [M [ MeOH]`~
2
ions obtained from them are a mixture of three isomeric
ions, 23-EZ, 31 and 17, which are formed by elimination
processes initiated by an a-cleavage (the former two)
and by a 1,4-elimination from the intact M`~ ions
involving one of the hydrogen atoms from position 4
(see Scheme 12).
The analysis of the results of CID measurements of
the cis-isomers 1c and 4c suggests the formation of an
[ MeOH]`~ and [M [ H O]`~ ions in each of the
2
two series.
The previously reported deuterium labeling study of
cis-3- and -4-phenylcyclohexyl acetates 8c and 9c has
shown major abstraction of hydrogen from the b-
positions in the course of the elimination of AcOH,
which is consistent with the expected McLa†erty-type
1,2-elimination.9 This pathway would lead to the forma-
tion of 4-phenylcyclohexene radical cation [19]`~ from
9c and of a mixture of [19]`~ and [18]`~ (the latter is
indistinguishable from [17]`~) from 8c. The results of
the CID measurements support the above suggestion
for 9c: the CID spectrum of its [M [ AcOH]`Õ ion is
identical with that of [19]`~ (r
\ 0.9980). On the
9ch19
other hand, the CID spectrum of cis-3-phenylcyclohexyl
acetate (8c) indicates the formation of [18]`~, which
Scheme 13.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

830
N. KHASELEV AND A. MANDELBAUM
Table 4. Relative
abundances
of
MH‘
and
[MH Ô ROH]‘ ions in the isobutane-CI mass
spectra of stereoisomeric 4-phenylcyclohexanols
and their methyl ethers and acetates
ÍMH˽
ÍMR ÉROH˽
ÍMH ÉROH˽/ÍMH˽
trans/cis
3c
3t
6c
6t
9c
9t
16
0.2
90
54
19
18
100
100
100
100
100
100
6.2
500
1.1
83
1.9
1.7
1.0
5.3
5.5
presumably rearranges to [17]`~, as the only elimi-
nation product (r \ 0.9990, \ 0.9985,
8ch19
r
8ch17
8ch18
r
\ 0.2558; see Scheme 13). No formation of
[19]`~ from 8c was indicated in this measurement. The
latter result indicates preferential abstraction of hydro-
gen from the homobenzylic position
2 and no
abstraction from position 6, in the course of this elimi-
nation process.
Scheme 14.
The above conclusion Ðnds support in the EI mass
spectral measurements of the stereospeciÐcally deute-
rium labeled acetates (2a)-d -8c, (2e)-d -8c, (6a)-d -8c
1
1
1
and (6e)-d -8c (Scheme 14). Only the Ðrst two iso-
1
topomers, (2a)-d -8c and (2e)-d -8c, deuterium labeled
at C-2, exhibit partial elimination of AcOD, whereas the
1
1
other two, (6a)-d -8c and (6e)-d -8c, with the label at
1
1
position 6, undergo exclusive elimination of AcOH. The
[M [ AcOH]`~/[M [ AcOD]`~ ion abundance ratios
in the mass spectra of (2a)-d -8c and (2e)-d -8c show
1
1
preferential abstraction of the equatorial hydrogen
atom in the course of this elimination process. The
latter result is consistent with the reported stereospeciÐ-
city of the McLa†erty rearrangement and of related
processes
butylcyclohexanes.20
The analysis of the results of the CID measurements
in
various
trans-4-substituted
tert-
Scheme 15.
Figure 10. CID spectra (30 eV collision energy, relative ion abundances (%) normalized to the most abundant ion) of the m/z 159
ÍMH ÉH OË½Õ ions, obtained upon isobutane-CI from stereoisomeric 2-, 3- and 4-phenylcyclohexanols: (a) 1c; (b) 1t; (c) 2c; (d) 2t; (e)
3c; (f) 3t.
2
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
831
of 2-phenylcyclohexyl acetates (7c and 7t) show that the
elimination of acetic acid in these two stereoisomers
gives rise to the same product ion [17]`~
(indistinguishable
from
[18]`~,
r \ 0.9992,
\ 0.9789,
7ch17
Scheme 16.
7ch7t
r
r
\ 0.9998,
r
\ 0.9956,
r
isomeric and stereoisomeric precursors.
7ch18
7th17
7th18
\ 0.9849). This result might be interpreted as an
It has often been stated that mass spectral stereoche-
mical e†ects observed in stereoisomers are pronounced
under CI conditions, which are less energetic than those
upon EI.22 The above results show that this proposed
generalization, which is often true, does not hold in the
case of the isomeric phenylcyclohexanol methyl ethers
and their acetates. The cyclic transition states, which are
involved in the mechanistic pathways of the EI-induced
lower energy eliminations from the cis-isomers
(speciÐcally involving the benzylic hydrogens in these
particular stereoisomers), result in highly stereospeciÐc
behavior upon EI. On the other hand, the elimination
processes occurring under CI conditions are simple
CÈO bond dissociations, and they involve the external
proton in both cis- and trans-isomers. The quantitative
di†erence between the stereoisomers results in this case
from the small di†erence (slightly above 1 kcal/mol (1
kcal \ 4.184 kJ)20) in the thermochemical stability of
the MH` ions.
indication of a common route of elimination in 7c and
7t. However, deuterium labeling of the benzylic position
shows that the elimination of acetic acid occurs via dis-
tinctly di†erent mechanistic pathways in the two stereo-
isomeric acetates (Scheme 15). The benzylic hydrogen
(at position 2) is largely involved in the elimination only
in the trans-acetate 7t, whereas exclusive abstraction of
a hydrogen from position 6 occurs in the cis-isomer 7c.
Elimination upon chemical ionization
The isobutane-CI mass spectra of the stereoisomeric
pairs of 4-phenylcyclohexanols 3 and their methyl
ethers 6 and acetates 9 a†ord most abundant m/z 159
[phenyl-C H ]` cations by the elimination of H O,
6 10
2
MeOH and AcOH, respectively, from the MH` ions.
The ion abundance ratios (shown in Table 4) are sys-
tematically higher in the isobutane-CI mass spectra of
the trans-isomers. The di†erence between the stereoiso-
mers is relatively large in the alcohols, but much smaller
in the case of the ethers and acetates. This distinctive
behavior, which indicates greater stability for the MH`
ions of the cis-isomers, may be explained by the internal
hydrogen bonding between the oxygen functions and
the phenyl ring, which is possible only in the cis-
conÐguration. This behavior is consistent with the
reported higher proton affinities of cis-4-phenylcyclo-
hexyl methyl and ethyl ethers, as compared with the
trans-epimers.21
CONCLUSIONS
The results of this study demonstrate the power of the
CID methodology in deducing detailed structural and
mechanistic information in the chemistry (and
stereochemistry) of gas-phase ions. It is important to
note that the majority of the gas-phase isomeric phenyl-
C H radical cations, formed either by EI-induced frag-
mentation of stereoisomeric phenylcyclohexyl deriv-
6 9
atives or by EI of a variety of phenyl-C H isomers,
retain their structural integrities. This behavior indi-
The CID spectra of the m/z 159 ions obtained from
the three cisÈtrans pairs of 2-, 3- and 4-
phenylcyclohexanols 1È3 (presented in Fig. 10) show a
6 9
cates relatively high energy barriers for the hydrogen
transfer processes and for some skeletal rearrangements,
which would result in the formation of the thermody-
namically most stable species in the EI mass spectra of
the phenylcyclohexyl derivatives and of the isomeric
standards studied in this work. On the other hand, the
CID spectra of the even-electron phenyl-C H` ions,
produced by the CI-induced fragmentation from isom-
eric phenylcyclohexanols and their methyl ethers and
acetates, show a high degree of similarity, suggesting
loss of structural information under CI in this system.
single fragment at m/z 91 (C H ` product ion). This
7 7
similar behavior of all the isomers suggests isomer-
ization of the m/z 159 ion to a common structure in the
course of the elimination processes. The simplicity of
the CID spectra of the m/z 159 ions is consistent with
the 1-phenylcyclohexyl structure of these ions (Scheme
16). The variation in the ion abundance ratios [m/z
91]`/[m/z 159]` in the CID spectra may be due to the
di†erent internal energies of the m/z 159 ions when
obtained upon CI by di†erent pathways from di†erent
6 10
EXPERIMENTAL
Table 5. CID mass spectra of [MH Ô ROH]‘ ions obtained
from stereoisomeric 4-phenylcyclohexanols and their
methyl ethers and acetates upon isobutane-CI
Mass spectrometry
MH ÉROH˽
m/z 91
EI- and CI-GC/MS analyses and CID measurements
were carried out on a Finnigan TSQ-70B triple-stage
quadrupole mass spectrometer. Separations by GC were
performed on a DB-5 (0.25 lm Ðlm thickness) 30
m ] 0.25 mm i.d. capillary column. The column tem-
perature was programmed from 60 to 280 ¡C at 15È
20 ¡C min~1. The scan rate was 0.7 scan s~1. EI
measurements were performed at 70 eV and 150 ¡C ion
source temperature. CI measurements were performed
at 120 eV, 150 ¡C ion source temperature and 0.4 Torr
1c
1t
2c
2t
3c
3t
6c
6t
9c
9t
100
100
100
100
100
100
100
100
100
100
46.1
22.1
38.7
41.4
22.5
40.3
52.3
41.6
37.6
40.1
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

832
N. KHASELEV AND A. MANDELBAUM
(indicated) reagent gas pressure (1 Torr \ 133.3 Pa).
CID measurements were performed with argon as the
target gas (0.3 mTorr, indicated) at 30 eV collision
energy (indicated). All data presented for each system
were obtained on a single day under identical condi-
tions, in order to ensure reliable comparisons.
The computer-aided calculation of the relative contri-
butions of the CID spectra of various standards was
performed by minimization of the sums of mean
squared di†erences between the intensity values of the
simulated and the experimental spectra. The mini-
mization was achieved by a standard procedure using
the algorithm of Powell.23
Lactone 10c. THP-ether of ethyl 4-hydroxycyclohexa-
necarboxylate (2.1 g, prepared with the use of pyridin-
ium p-toluenesulfonate (PPTS)39) was added dropwise
to
a THF solution of lithium diisopropylamide
(generated from n-butyllithium (5.25 ml of a 1.6 M solu-
tion in hexane) and diisopropylamine (1.3 ml, 9.3 mmol)
in 15 ml of THF) at [78 ¡C under nitrogen. The
mixture was warmed to 0 ¡C and stirred for 15 min, 20
ml of HMPA were added and a solution of 1.78 g of
n-benzenechromium tricarbonyl in 25 ml of THF was
added over 5 min at [78 ¡C. The resulting yellow solu-
tion was warmed to 0 ¡C, stirred for 30 min, cooled to
[78 ¡C, a solution of 8.5 g (33 mmol) of iodine in 25 ml
of THF was added and the mixture was allowed to
warm to room temperature and left overnight with stir-
ring. The THP-ether of ethyl 4-hydroxy-1-phenylcyclo-
hexanecarboxylate (36) was extracted with diethyl ether,
washed with 5% NaHCO , Na S O and, saturated
Materials
Tetrahydrofuran (THF), diethyl ether and benzene were
freshly distilled under nitrogen from sodium benzophe-
none prior to use. Hexamethylphosphoramide (HMPA)
was distilled from calcium hydride and stored over 13X
molecular sieves under argon.
Stereoisomeric 1È9,7h9 10a,24 12,25 13,25 14,26 15,26
16,27 17,28 18,29a 19,29,30 20,30 21,30 22,31 23,30 24,32
27,33 28,34 29,35 30,34,36 and 3137 were prepared by
routes reported in the literature.
3
2 2 3
NaCl, dried over MgSO and puriÐed by column chro-
4
matography with diethyl etherÈhexane (1 : 3). 1H NMR,
d 1.23 (t, 3H), 1.4È2.0 (m, 14 H), 3.5 (m, 2H), 3.85 (m,
1H), 4.1 (q, 2H), 4.67 (br s, 1H), 7.3 (m, 5H).
A solution of 36 and PPTS (1 g, 8 mmol) in ethanol
(4 ml) was stirred at 55 ¡C for 3 h. The solvent was
evaporated in vacuum and the residue was chromato-
graphed on a silica gel column to a†ord pure ethyl 1-
phenyl-4-hydroxycyclohexanecarboxylate. This material
was treated with 7% H SO , extracted with diethyl
Lactones 10b and 10c were prepared following routes
shown in Scheme 17.
2
4
ether, washed with saturated NaCl solution, dried over
Lactone 10b.38 Phenylmagnesium bromide, prepared
from 0.1 g (4.6 mmol) of magnesium turnings and 0.7 g
(4.6 mmol) of bromobenzene in 10 ml of dry diethyl
ether, was added drop-wise to a solution of 0.65 g (3.8
mmol) of ethyl 4-oxocyclohexanecarboxylate (35)
MgSO , concentrated under vacuum and the resulting
4
yellow oil was chromatographed on silica gel with 1 : 4
diethyl etherÈhexane to yield 10c. 1H NMR, d 1.8È2.25
(m, 8H), 4.76 (s, 1H), 7.8 (m, 5H).
(prepared by CrO
oxidation of ethyl 4-
3
hydroxycyclohexanecarboxylate) in 20 ml of diethyl
ether. The white precipitate was dissolved in THF, the
solution was stirred for 3.5 h, cooled to [5 ¡C,
quenched with ice-cold 7% sulfuric acid and stirred
overnight. The reaction mixture was extracted with
diethyl ether, washed with saturated NaCl solution,
25-E and 25-Z. (E)- and (Z)-3-phenyl-1,3-hexadienes 25-E
and 25-Z were prepared following the route shown in
Scheme 18.
Propylphosphonic dichloride (4 g, prepared by the
reaction of 1-bromopropane with phosphorus tri-
chloride and aluminum chloride) in diethyl ether was
added to a solution of 2.5 g of s-dimethylethyl-
enediamine in 200 ml of anhydrous diethyl ether and 50
ml of triethylamine with stirring at 0 ¡C under a nitro-
gen atmosphere and the solution was stirred for 3 h at
0 ¡C and overnight at room temperature. Addition of
methylene chloride (50 ml) followed by Ðltration and
evaporation yielded 3.12 g (73%) of N,N@-dimethyl-2-
propyl-1,3,2-diazaphospholidene 2-oxide (37). 1H NMR,
d 3.1 (m, 4H), 2.61 (d, J \ 9.5 Hz, 6H), 2.2 (m, 2H), 1.1
(d, J \ 15 Hz, 3H), 1.2 (d, J \ 15 Hz, 2H).
dried over MgSO , concentrated under vacuum, and
4
the resulting yellow oil was chromatographed on silica
gel with 1 : 4 diethyl etherÈhexane to yield 45% of 10b.
IR (Ðlm) 1720, 1680 cm~1; 1H NMR, d 1.8È2.25 (m,
8H), 2.76 (s, 1H), 7.39 (m, 5H).
n-BuLi (1.6 M in hexane, 2 ml) was added at [78 ¡C
to a stirred solution of 0.5 g (2.8 mmol) of 37 in 20 ml of
THF and 5 ml of HMPA under a nitrogen atmosphere.
The solution was stirred for 30 min and 0.5 ml of 1-
phenyl-2-propen-1-one (38) was added. After stirring for
2 h at [78 ¡C, the solution was allowed to warm to
[20 ¡C, stirred for an additional 2 h, allowed to warm
to room temperature, 0.5 ml of water was added and
the reaction mixture was extracted with CH Cl . The
2
2
resulting mixture of stereoisomers 39a and 39b was
separated on a silica gel column (diethyl etherÈhexane
(1 : 4) as eluent). 1H NMR of 39a, d 7.4 (m, 5H), 5.9È6.8
(m, 3H), 5.4 (br s, 1H), 3.0È3.3 (m, 4H), 2.68 (d) and 2.74
Scheme 17.
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
833
Scheme 18.
(d, J \ 9 Hz) superimposed on 2.5È2.9 (m, PCH) (total
7H), 1.2 (m, 2H), 0.92 (m, 3H). 1H NMR of 39b, d 7.3 (m,
5H), 5.9È6.8 (m, 3H), 5.1 (br s, 1H), 2.8È3.0 (m, 4H), 2.6
(d) and 2.71 (d, J \ 9 Hz) superimposed on 2.5È2.7 (m,
PCH) (total 7H), 1.0 (m, 2H), 0.9 (m, 3H).
Freshly distilled tetrahydropyran (THP, 5 ml) was
added to a solution of 2-phenylcyclohexanol (1.3 g) and
pyridinium p-toluenesulfonate (PPTS, 1 g) in 5 ml of
CH Cl below 5 ¡C, and the reaction mixture was
2
2
stirred for 6 h at room temperature. Extraction
(CH Cl ) a†orded the THP-ether, which was used
A benzene (4 ml) solution of a mixture of 39a and 39b
(0.35 g) and triethylamine (1 ml) was stirred and
reÑuxed for 4.5 h, then the solvent was evaporated. The
residue was extracted with pentane and the solvent was
evaporated. Bulb-to-bulb distillation in the presence of
anhydrous potassium carbonate gave a mixture of the
two geometrical isomers 25-E and 25-Z as a clear liquid
(yield 42%), which was separated by preparative TLC
(diethyl etherÈhexane (1 : 3). 1H NMR of 25-Z, d 1.0 (t,
3H), 2.1 (m, 2H), 5.20 (d, J \ 10 Hz, 1H), 5.27 (d, J \ 16
Hz, 1H), 5.65 (m, 1H), 6.55 (m, 1H), 7.25 (m, 5H). 1H
NMR of 25-E, d 1.1 (t, 3H), 2.1 (m, 2H), 5.21 (d, J \ 11
Hz, 1H), 5.3 (d, J \ 17 Hz, 1H), 6.01 (m, 1H), 6.57 (m,
1H), 7.3 (m, 5H).
2
2
without further puriÐcation (98% pure by GC/MS, yield
99%). The THP-ether (1.9 g), NaH (0.2 g) and DMSO-
d (5.5 ml) were reÑuxed for 3 h. Extraction (CH Cl )
6
2 2
and puriÐcation of the residue on a small silica gel
column (elution with hexane to remove DMSO and
then hexaneÈethyl acetate (3 : 1) yielded the deuterium-
labeled THP-ether ([96% deuterium content by
GC/MS). The protection group was removed by stirring
in ethanol solution in the presence of PPTS (1 g) at
55 ¡C for 3 h. Acetylation (acetyl chloride in pyridine) of
the resulting 2-d-2-phenylcyclohexanol a†orded
a
mixture of the two stereoisomeric acetates (2a)-d -7c
1
and (2a)-d -7t.
1
26-E and 26-Z. n-BuLi (20% in hexane, 3.5 ml) was
Acetates d -8c (Scheme 14). The stereospeciÐcally labeled
1
added dropwise to
a
stirred slurry of 3-
acetates (6a)-d -8c, (6e)-d -8c, (2a)-d -8c and (2e)-d -8c
1 1 1
1
butenyltriphenylphosphonium bromide (4 g) in 10 ml of
dry diethyl ether under a nitrogen atmosphere. After 2 h
of stirring at room temperature, phenylacetaldehyde (1.4
ml) dissolved in 10 ml of diethyl ether was added slowly
were prepared by routes shown in Scheme 20.
Boron triÑuoride etherate (7 ml) was added dropwise
over 10 min to a solution of NaBD (1.3 g) and 4-
4
phenylcyclohexene (3 g) in diglyme (35 ml) in an ice-
and the mixture was stirred overnight. Et O was added
to the mixture and the precipitate formed was removed
bath under N . The reaction mixture was stirred for
another 2 h at room temperature, cooled to 0 ¡C and 3
2
2
by Ðltration. The organic phase was washed with water,
M NaOH (10 ml) was added rapidly. Subsequently, 30%
dried over MgSO and the solvent was removed under
H O (10 ml) was added slowly with stirring at [10 ¡C,
4
2 2
vacuum to a†ord 2.1 g of a mixture of 26-E and 26-Z
the reaction mixture was stirred for 3 h, the layers were
(38% yield), which was separated on a silica gel column
separated, the aqueous layer was extracted with diethyl
impregnated with AgNO with diethyl etherÈhexane
3
(1 : 20) as eluent.
Synthesis of deuterium-labeled compounds
Acetates (2a)-d -7c and (2a)-d -7t (Scheme 15). 2-Phenyl-2-
1
1
d -cyclohexanols were prepared by the exchange of the
1
benzylic hydrogen by heating the tetrahydropyranyl
ether39 of 2-phenylcyclohexanol (mixture of cis- and
trans-isomers) with dry hexadeuterodimethyl sulfoxide
(DMSO-d ) and sodium hydride (Scheme 19).
Scheme 19.
6
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

834
N. KHASELEV AND A. MANDELBAUM
Scheme 20.
ether and the organic layers were dried over MgSO
Hydroboration of 3-phenylcyclohexene led to the for-
mation of cis- and trans-3-phenyl-cis-2-d-cyclohexanol
(45 and 46) and trans- and cis-2-phenyl-cis-6-d-cyclo-
hexanol (47 and 48), which were separated on a silica
gel column followed by fractional crystallization of
dinitrobenzoates (Ðnal separation of the axial alcohols
46 and 48) and their hydrolysis. Oxidation of alcohol 46
4
and evaporated. The resulting mixture of cis-3-phenyl-
cis-6-d-cyclohexanol (40), trans-3-phenyl-cis-6-d-cyclo-
hexanol (41), trans-4-phenyl-cis-2-d-cyclohexanol (42)
and cis-4-phenyl-cis-2-d-cyclohexanol (43) was separat-
ed by chromatography on a silica gel column with
acetoneÈhexane (1 : 3) as eluent. Final separation of 41
and 43 was achieved by fractional crystallization of
their 3,5-dinitrobenzoates, followed by mild basic
hydrolysis.
with CrO followed by reduction and separation led to
3
cis-3-phenyl-trans-2-d-cyclohexanol (49). Acetylation
(acetyl chloride in pyridine) of 45 and 49 gave rise to the
corresponding acetates, (2a)-d -8c and (2e)-d -8c.
trans-3-Phenyl-cis-6-d-cyclohexanol (41) was oxidized
to the corresponding 3-phenyl-cis-6-d-cyclohexanone by
reaction with CrO in pyridineÈCH Cl solution.40
1
1
3
2 2
Reduction with excess of LiAlH in THF a†orded a
4
Acknowledgements
mixture of cis- and trans-3-phenyl-cis-6-d-cyclohexanol
(41 and 44), which was separated on a silica gel column
with acetoneÈhexane (1 : 3) as eluent. Acetylation (acetyl
chloride in pyridine) of 40 and 44 gave rise to the corre-
sponding acetates, (6a)-d -8c and (6e)-d -8c.
This work was supported by the Fund for Promotion of Research at
the Technion. We are grateful to Dr V. Ryaboy for his help with the
computer-aided analysis of the CID spectra and to Mr A. Etinger for
assistance with the mass spectral measurements.
1
1
( 1998 John Wiley & Sons, Ltd.
J. Mass Spectrom. 33, 819È835 (1998)

CID OF EI STEREOSPECIFIC ELIMINATION IN PHENYLCYCLOHEXANOLS
835
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J. Mass Spectrom. 33, 819È835 (1998)