Mass spectra of new heterocycles: VII. Main fragmentation channels of 2-(methylsulfanyl)-4,5-dihydro-3H-azepines under electronic ionization

Article abstract of DOI:10.1134/S1070428009020237

Mass spectra of 3,7-di- and 3,6,7-trisubstituted 2-(methylsulfanyl)-4,5- dihydro-3H-azepines were investigated for the first time. The fragmentation of molecular ions of 3-alkoxy-substituted dihydroazepines follows the rules characteristic of ethers. The

Full text of DOI:10.1134/S1070428009020237

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 2, pp. 292−303. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © L.V. Klyba, N.A. Nedolya, O.A. Tarasova, E.R. Zhanchipova, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 2, pp. 301−312.
Mass Spectra of New Heterocycles: VII.* Main Fragmentation
Channels of 2-(Methylsulfanyl)-4,5-dihydro-3H-azepines
under Electronic Ionization
L. V. Klyba, N.A. Nedolya, O. A. Tarasova, and E. R. Zhanchipova
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
Irkutsk, 664033 Russia
e-mail: nina@irioch.irk.ru
Received April 23, 2008
Abstract—Mass spectra of 3,7-di- and 3,6,7-trisubstituted 2-(methylsulfanyl)-4,5-dihydro-3H-azepines were
investigated for the first time. The fragmentation of molecular ions of 3-alkoxy-substituted dihydroazepines
follows the rules characteristic of ethers. The fragmentation of [M]+· of 3-phenyldihydroazepine occurred through
a sequence of rearrangements; one of them led to the formation of a stable ion [M – MeS]+. A specific feature of
the fragmentation of 3-(pyrrol-1-yl)dihydroazepine under the electronic ionization consists in the formation of ion
[M – Me]+ with the charge mainly localized on the pyrrole ring.Apartial decomposition at heating of 3-alkoxy-4,5-
dihydro-3H-azepines (with alkanol elimination) resulted in 7-(methylsulfanyl)-3H-azepines. The latter under the
electronic ionization give a stable molecular ion whose primary fragmentation involves the elimination of MeS
group or its fragments.
DOI: 10.1134/S1070428009020237
Seven-membered heterocycles, azepines, and their
versatile derivatives attract strong interest first of all due
to their spread in natural objects [2] and to their
applications to medical practice and pharmacology [3].
These are both azepine alkaloids and unique drugs of
psychotropic, antidepressant, anticonvulsive and other
actions used in the treatment of grave diseases like
epilepsy, schizophrenia, Alzheimer’s disease, and also
cancer, AIDS and many others. Besides this class
compounds are employed as important synthetic
intermediates, ligands, optically active substances [4].
In this connection a considerable attention is directed to
the development of new convenient synthetic procedures,
to the extension of their number, and to detailed study of
their characteristics, including spectral ones.
“Precise” (excluding or minimizing the concurrent forma-
tion of structural isomers: pyrroles and 2,3-dihydro-
pyridines) thermally induced [1,5]-sigmatropic rear-
rangement of the primary reaction products formed in
the reaction of allene carbanions with isothiocycnates,
1-aza-1,3,4-trienes, afforded the target 2-aza-1,3,5-trienes
I that under the action of t-BuOK easily transformed
into formerly unknown and hardly available by other
procedures 2-(methylsulfanyl)-4,5-dihydro-3H-azepines
II–VII [6].
In the previous communication [1] we studied for the
first time and described the mass spectra of the first
representative of the new family of 2-(methylsulfanyl)-
4,5-dihydro-3H-azepines, 7-methyl-2-(methylsulfanyl)-3-
methoxy-4,5-dihydro-3H-azepine (IIIa) and its structural
isomers, formerly unknown 1-isopropyl-2-(methyl-
sulfanyl)-3-methoxypyrrole and 2,2-dimethyl-6-(methyl-
sulfanyl)-5-methoxy-2,3-dihydropyridine obtained from
the α-lithiated methoxyallene, isopropyl isothiocycnate,
and methyl iodide.As should be expected, the most stable
molecular ion formed from the substituted pyrrole (relative
intensity of the peak 100%). The intensity of the
We recently discovered a fundamentally new
approach to designing azacycloheptadienes (dihydro-
azepines) and azacycloheptatrienes (azepines) from
available allenes or alkynes, isothiocyanates and alkylating
agents. The procedure includes two preparative stages: the
synthesis [5] and deprotonation (by treatment witht-BuOK)
[6] of conjugated 2-aza-1,3,5-trienes I (Scheme 1).
*For Communication VI, see [1].
292

MASS SPECTRA OF NEW HETEROCYCLES: VII.
293
Scheme 1.
t-BuOK
t-BuOK
OAlk
OMe
SMe
R1 = OAlk,
R3 = Me
R1 = OMe,
R2
II, IIIà_IIId, IV
SMe
N
N
R2, R3 = (CH2)4
V
(1) 2 BuLi, THF_hexane
(2) Me2CHN=C=S
(3) t-BuOH
(4) MeI
(5) [1,5]-H shift
(1) BuLi, THF_hexane
(2) R2R3CHN=C=S
(3) MeI
R1
R1
(4) [1,5]-H shift
R1
R3
R2
C
N
SMe
R1 = OMe (à), OEt (b),
OPr-i (c), OBu-t (d)
R1 = Ph, pyrrol-1-yl
I
R1 = Ph,
R2 = R3 = Me
R1 = pyrrol-1-yl,
R2 = R3 = Me
t-BuOK
N
N
VII
N
Me
SMe
Me
SMe
VI
molecular ions of 2,3-dihydropyridine and 4,5-dihydro-3H-
azepine (IIIa) are comparable: 50 and 58% respectively.
It was established that the primary fragmentation act
under the electronic ionization (70 eV) was the same in
all the heterocyclic isomers and consists in the rupture of
a methyl radical. Therewith the ion [M– Me]+, m/z 170
(42%) formed by the fragmentation of the molecular ion
of 4,5-dihydro-3H-azepine (IIIa) was less stable than
its five-membered and six-membered analogs. Further
fragmentation of the ion [M – Me]+ alongside the
elimination of NCS radical leading to the diagnostic ion
with m/z 112 (100%) consists in the contraction of the
seven-membered heterocycle into a five-membered ring
forming an ion [M – Me – C2H4]+, m/z 142 (9%).
rules found for the fragmentation of the molecular ion of
4,5-dihydro-3H-azepine (IIIa) [1] were general we
applied GC–MS method to a wider set (nine compounds)
of previously unknown 3-alkoxy-, 3-phenyl-, and 3-(1-
pyrrolyl)-substituted 2-(methylsulfanyl)-4,5-dihydro-3H-
azepines (Scheme 1) for elucidation of their behavior under
electronic ionization (70 eV).
The analysis of mass spectra showed that all studied
4,5-dihydro-3H-azepines II–VII under electronic ioniza-
tion formed in registered amount molecular ions [M]+·
whose stability unexpectedly strongly depended on the
structure and the nature of substituents in the positions 3
and 7. For 3-alkoxy-4,5-dihydro-3H-azepines II–V the
intensity of peaks [M]+· varied from 13 (for compound
IIId) to 90% (for compound V). The presence in the
structure of 4,5-dihydro-3H-azepines II–V of two hetero-
atomic substituents (alkoxy and alkylsulfanyl groups)
makes it possible to consider them not only like azacyclo-
heptadienes but also like ethers and sulfides. Con-
sequently, same as in the case of their five-membered
and six-memebered heterocyclic structural isomers (pyr-
roles and 2,3-dihydropyridines [1]) containing similar
heteroatomic substituents, the fragmentation of the
molecular ions of compounds II–V should fit not only to
the rules characteristic of azaheterocycles (with the
localization of the ion-radical site on the nitrogen) but
those governing the fragmentation of ethers and/or
We have not found other publications on the purposeful
and detailed studies of mass spectra of dihydroazepines
including 4,5-dihydro-3H-azepines. Mass spectra of three
penta- and hexa-substituted 4,5-dihydro-1H-azepines
containing as substituents Me, MeO, MeCO2, CN, and
2,5-pyrrolidin-1-yldione group were published in Mass
Spectral Database (NIST/EPA/NIH). But they are
unsuitable for comparison with the spectra of the objects
of this study.
In this study in continuation of the systematic
investigation of the mass spectra of new heterocycles
generated from lithiated allenes or alkynes and
isothiocyanates [1, 7–10] in order to reveal whether the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

KLYBA et al.
294
sulfides (with the localization of the charge on oxygen or
sulfur respectively). For instance, the primary fragmenta-
tion of molecular ions of 2-(alkylsulfanyl)pyrroles lacking
substituents in the position 3 occurred by the sulfide
mechanism (with the rupture of C–S bonds) [8]. In
contrast, the rupture of C–N bonds in the nitrogen-
containing substituent, namely, the amine fragmentation,
occurred at the electronic ionization in the isomeric to
2-(alkylsulfanyl)pyrroleas N-alkyl- and N,N-dialkyl-2-
thiophenylamines [9]. Especially strong effect of a hetero-
atomic substituent (and of the character of the heteroatom
therein: N, S) on the direction and the character of
molecular ions fragmentation we observed investigating
the mass spectra of 2-(N-alkyl-N-methylamino)-3-
phenylthiophenes and their structural isomers, 3-alkyl-4-
methylene-2-(N-methylimino)-3-phenylthietanes and 3-
(alkylsulfanyl)-1-(N-methylimino)-2-phenyl-2-cyclo-
butenes [10] synthesized from 1,3-dilithiopropargyl-
benzene, methyl isothiocyanate, and alkyl halides [11].
Inasmuch as the objects of the present study belong
simultaneously to three chemical classes of compounds
(compounds II–V to dihydroazepines, ethers, and sulfides;
compound VI to dihydroazepins, sulfides, and benzenes;
compound VII to dihydroazepines,sulfides, and pyrroles)
the fragmenta-tion of their molecular ions might follow
beside the already mentioned directions also quite
unpredicted routes.
The study of molecular ions fragmentation of
3-methoxy-substituted 4,5-dihydro-3H-azepines II, IIIa,
IV, and V differing by the structure of substituents in the
positions 6 and 7 of the heterocycle showed that for all
studied structures, both for 6,7-unsubstituted [R2 = R4 =
H (II)], for 7-alkyl-substituted [R4 = H: R2 = Me (IIIa),
Et (IV)], and for 6,7-fused system [R2,R4 = (CH2)3 (V)]
the fragmentation of molecular ions occurred by common
channels forming diagnostic ions (Scheme 2, Table 1)
[1].
The main fragmentation channel of molecular ions of
3-methoxydihydroazepines was apparently the decomposi-
tion of the heterocycle with ejection of methyl thiocycnate
Scheme 2.
[C3O(R2 _ H)R4]+
G
R4
R4
O
_HCN
_CO
+
+
N
R2
N
SMe
R2
SMe
R4
R2
O
H
H
A2
D2
+
_MeSH
R4
N
E
+
+
OH
R4
R2
OH
R2
SMe
N
A
SMe
N
D
+.
R4
R2
OMe
SMe
_C2H4
_Me.
R4
OMe
S
N
R4
R2
OMe
II, IIIa, IV, V, M+.
+
R2
N
+
_MeSCN
H
N
S
H
D1
A1
+.
R4
R2
OMe
+.
R4
OMe
N
_HCS.
_NCS.
R2
F
C
[C3H2OR2R4]+.
[C3N(R2 _ H)R4]+.
_MeOH
_HCN
H
I
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MASS SPECTRA OF NEW HETEROCYCLES: VII.
295
Table 1. Principal characteristic ions in the mass spectra of 4,5-dihydro-3H-azepines II, IIIa, IV, and V
m/z (Irel, %)
Ions
IIIà [1]
II
IV
V
[M]+·
171 (32)
185 (59)
199 (88)
211 (90)
A, A1, À2
[M – Me]+
[M – MeS]+
[M – MeSCN]+· or [À – NCS]+·
[À – C2H4]+ or [D2 – CÎ]+
[D – MeSH]+
[D1 – HCS]+·
[E – HCN]+
[F– HCN]+ ·
[E– MeOH]+ ·
156 (30)
124 (24)
98 (100)
128 (6)
80 (21)
83 (6)
170 (42)
138 (10)
112 (100)
142 (9)
94 (11)
97 (12)
67 (11)
70 (60)
65 (9)
184 (57)
152 (20)
126 (100)
156 (10)
108 (16)
111 (18)
81 (14)
84 (10)
79 (22)
134 (18)
(7)
196 (48)
164 (38)
138 (25)
168 (0)
120 (11)
123 (4)
93 (6)
B
C
D, D1, D2
E
F
53 (22)
56 (9)
G
H
I
96 (2)
51 (7)
91 (15)
146 (23)
[B – H2O]+
106 (11)
(23)
120 (10)
(12)
J
K
L
M
[B – R2CN]+, m/z 97
[K – Ñ2Í2]+, m/z 71
[K – Ñ2Í4Î]+, m/z 53
(20)
(17)
(26)
(100)à
(22)
(56)
(39)
a
This ion might form due to the fragmentation of the open-chain form of molecular ion [M2]+· with the charge localized on the oxygen atom
(Scheme 5).
(or methyl isothiocyanate) molecule resulting in an odd-
electron ion [M – MeSCN]+· (C). In the spectra of
compounds II, IIIa, and IV this peak has the maximum
abundance. The relatively abundant ions [M – Me]+ (A,
A1, A2) formed after elimination of the methyl radical
(with the rupture of O–Me and S–Me bonds) eject an
ethylene molecule giving ions [M – Me – C2H4]+ (D,
D1) or C=O species giving ion [M – Me – CO]+ (D2)
The further fragmentation of these ions can occur in two
directions, either with the loss of a methanethiol molecule
(E) or of HCS radical (F). The elimination of NCS radical
from ions A also leads to diagnostic ion C.
One more channel of sulfide fragmentation of the
molecular ion of 3-methoxy-4,5-dihydro-3H-azepines
consists in the rupture of the heterocycle–S bond and
ejection of methylsulfanyl radical (Scheme 3). The arising
ion [M – MeS]+ (B) and the products of its further
decomposition (ions J–M) significantly contribute to the
total ion current (Table 1).
The fusion of 4,5-dihydro-3H-azepines increased the
stability of the molecular ion whose peak is second in
abundance (90%) in the spectrum of compound V. Besides
this spectrum was characterized by the presence of
intense ion peaks corresponding to the fragmentation of
Scheme 3.
+.
+
OMe
OMe
[C7H7NR2]+
_H2O
_MeS.
R2
II, IIIa, IV, M+.
SMe
R2
N
N
J
B
_R2CN
[C4H7O]+
[C4H5]+
+
_C2H2
_C2H4O
OMe
M, m/z 53
L, m/z 71
K, m/z 97
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

KLYBA et al.
296
ion B with m/z 164 that were not observed in the other
spectra (Scheme 4).
examples of compounds IIIa–IIId (Schemes 2, 6, and
7). It turned out that in going from 3-methoxy- (IIIa) to
3-tert-butoxy-dihydroazepine (IIId), i.e., at increasing the
length and the bulk of the alkyl part of the alkoxy sub-
stituent the character of the molecular ion fragmentation
essentially changed (Table 2, Scheme 6).
In the spectrum of compound V the peak of maximum
abundance belonged to ion L with m/z 71 whose intensity
in the mass spectra of the other methoxy-substituted
4,5-dihydro-3H-azepines II, IIIa, and IV is essentially
lower, from 17 to 26% (Table 1). Presumably at ionization
and before the fragmentation the molecular ion of 4,5-di-
hydro-3H-azepine V suffered the isomerization into open-
chain structures with the opening of the heterocycle at
the C2–C3 bond and the separation of the cationic and
the radical sites. The charge may localize either on the
nitrogen (ion [M1]+·) or on the oxygen (ion [M2]+·)
(Scheme 5). In the first instance the fragmentation of
the molecular ion [M1]+· involved the rupture of the C7–
N bond and the formation of the diagnostic odd-electron
ion [M – MeSCN]+· (C) occurred whose peak as already
mentioned was the most strong in the spectra of com-
pounds II, IIIa, and IV.
For instance, unlike methoxy derivatives, the frag-
mentation of whose molecular ion involved all three
heteroatoms, the fragmentation of molecular ion of
compounds IIIb–IIId occurred through the channels
governed by the prevailing localization of the charge and
the lone electron on the ether oxygen. This statement is
confirmed, firstly, by the absence in the mass spectra of
3-alkoxy-dihydroazepines IIIb–IIId of peak of the ion
[M – MeSCN]+· which is the strongest in the spectra of
3-methoxy-4,5-dihydro-3H-azepines II, IIIa, and IV, and
also of ions A1 and B (sulfide fragmentation at Me–S
and heterocycle–S bonds respectively). Inasmuch as in
contrast to compounds II, IIIa, IV, and V the m/z values
of ions [M – MeSCN]+· and [M – Alk – NCS]+· (C) are
different for dihydroazepines IIIb–IIId (sinceAlk ≠ Me)
it is possible to determine unambiguously which of the
two possible channels provides ion C and in particular to
exclude the channel related to the ion [M – MeSCN]+·.
The fusion of 4,5-dihydro-3H-azepines shifted the
equilibrium to the formation of ion [M2]+· with the charge
localized on the oxygen atom. The rupture of C5–C6 bond
resulted in ion with m/z 71 (100%) in keeping with the
Stevenson– Audier rule [12].
The influence of the structure of the alkoxy substituent
on the fragmentation character of 7-methyl-2-(methyl-
sulfanyl)-4,5-dihydro-3H-azepines was investigated by
Secondly, the ether fragmentation type of the molecular
ions of alkoxy-substituted dihydroazepines IIIb–IIId is
confirmed by the fact that the primary reactions initiated
Scheme 4.
MeOH + m/z 132 (33)
MeO. + m/z 133 (7)
CH2O + m/z 134 (11)
CHO. + m/z 135 (6)
C2H4 + m/z 136 (10)
HCN + m/z 137 (7)
+
+.
OMe
OMe
_SMe.
N
N
SMe
V, M+., m/z 211 (90)
B, m/z 164 (38)
Scheme 5.
+
+.
OMe
OMe
OMe
+
N
N
N
SMe
SMe
SMe
+.
+.
M1
V, M+., m/z 211 (90)
M2
+.
OMe
+
CH2=CHCH=OMe
_MeSCN
L, m/z 71 (100)
C, m/z 138 (25)
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MASS SPECTRA OF NEW HETEROCYCLES: VII.
297
Table 2. Principal characteristic ions in the mass spectra of 3-alkoxy-7-methyl-(2-methylsulfanyl)-4,5-dihydro-3H-azepines IIIb–
IIId
m/z (Irel, %)
Ions
IIIb
IIIc
IIId
[M]+·
199 (31)
213 (44)
227 (13)
A, À2
C
D, D2
[M – Alk]+, m/z 170
[À5 – NCS]+·, m/z 112
[A – C2H4]+ or [A2 – CÎ]+, m/z 142
[D – MeSH]+, m/z 94
[E – HCN]+, m/z 67
[M – AlkOH]+, m/z 153
[M – CnH2n]+, m/z 171
(55)
(100)
(13)
(17)
(19)
(5)
(80)
(92)
(23)
(31)
(31)
(18)
(28)
(57)
(22)
(15)
(19)
(17)
(11)
(12)
E
G
[Ì3]+·, [Ì4]+·
–
À3
B1
[Ì3 – Me]+, m/z 156
[Ì3 – MeS]+, m/z 124
–
–
(11)
(16)
(7)
(8)
N
[Ì4 – MeCS]+ or [À3 – CS]+, m/z 112
[À3 – H2O]+, m/z 138
–
–
(92)à
(22)à
(21)
(8)
[B1 – H2O]+, m/z 120
[Ñ6Í9Î]+, m/z 97
–
(31)
(41)
(12)
(38)
(12)
[Ñ6Í11]+, m/z 83
[Ñ4Í7Î]+, m/z 71
[Ñ4H7]+, m/z 55
[Ñ4Í5]+, m/z 53
(7)
(11)
(15)
(34)
(70)
(3)
(5)
(11)
(21)
(23)
(36)
(58)
b
[Alk]+
43 (94)
(35)
57 (100)
(18)
[Ñ3Í6]+·, [Ñ2Í2Î]+·, [Ñ2Í4N]+, m/z 42
(19)
(97)
[Ñ3Í5]+, [Ñ2Í3N]+·, m/z 41
(100)
(100)
à Overlapped with the peak of ion-radical C. bMasses below m/z 35 were not registered.
by the radical center lead through the rupture of C–O
bond to ions [M – Alk]+ with m/z 170 (A and/or A2)
whose peaks are sufficiently intense (Table 2). Further
fragmentation of ion A occurs by channels described for
the methoxy analogs (cf. Schemes 2 and 6).
alkoxydihydroazepines IIIb–IIId leads to the appearance
of two new channels of [M]+· fragmentation involving
the elimination of (CnH2n, n > 2) or alkanol molecules
(Scheme 6). The odd-electron ion [M – CnH2n]+· with m/
z 171 ([M3]+·) most probably has the structure of 7-methyl-
2-(methylsulfanyl)-4,5-dihydro-3H-azepin-3-ol (VIII).
The main directions of fragmentation of this cation-radical
consist in the rupture of the C–S bond and the formation
of ions [M3 – Me]+ with m/z 156 (A3), [M3 – MeS]+ with
m/z 124 (B1), and also of ion [M4 – MeCS]+ with m/z
112 (N) originating apparently from the open-chain form
of the molecular ion [M4]+· (Scheme 6). Hence in contrast
to methoxy- (II, IIIa, IV, V) and alkoxy- (IIIb–IIId)
dihydroazepines the fragmentation of the molecular ion
of 4,5-dihydro-3H-azepin-3-ol (VIII) is more like the
sulfide type of fragmentation. The spectrum of compound
IIIb lacks the peak of ion [M – CnH2n]+· with m/z 171,
Besides for alkoxy-substituted dihydroazepines IIIc
and IIId the formation of ions [Alk]+ was characteristic,
since owing to their branching these ions possessed
a considerable thermodynamic stability. Especially feasible
became the bond ruptures giving tertiary cation [13]. For
instance, peaks of ion [C(Me)3]+ with m/z 57 and products
of its fragmentation prevail in the spectrum of compound
IIId.
Mass spectra of alkyl ethers with large alkyls are
commonly characterized by abundant peaks of odd-
electron fragments [14]. The growing alkyl group in
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KLYBA et al.
298
Scheme 6.
+
OH
+
N
E, m/z 94
G, m/z 67
Me
SMe
_C2H4
_HCN
+.
_MeSH
Me
SMe
_CO
N
H
D2, m/z 142
D, m/z 142
+.
+
OH
OAlk
O
_Alk.
_AlkOH
+
N
N
N
N
Me
SMe
Me
SMe
A, m/z 170
Me
SMe
Me
SMe
IIIb_IIId, M+.
H
A2
m/z 153
_CnH2n
for IIIc, IIId
+
OH
+.
+
OH
OH
H2O + m/z 138
_Me.
_MeS.
N
N
N
Me
Me
SMe
Me
Me
S
H
B1, m/z 124
A3, m/z 156
VIII, M3+., m/z 171
_CS
C3H6 + m/z 42
H2O + m/z 94
H2O + m/z 120
+
OH
HCN + m/z 97
_MeCS.
.
.
MeCN + m/z 83
+
OH
HCO + m/z 83
N
SMe
N
Me
+.
MeCN + m/z 71
M4
N, m/z 112
Scheme 7.
+.
+.
+
+
OAlk
O
OMe
_NCS.
_Alk.
SMe
Me
S
OMe
.
S
N
N
N
Me
Me
Me
Me
B, m/z 112
A4, m/z 170
A5
IIIà_IIId, M+.
The fragmentation of the cation-radical [M –AlkOH]+·
with m/z 153 will be discussed in detail further
(Scheme 11).
and the peak of ion with m/z 112 is the most abundant.
Consequently, it is not ion N (Scheme 6), and its formation
occurs along another mechanism. Presumably, ion with
m/z 112 has the structure of ion C (Scheme 7), and its
appearance is due to the skeletal rearrangement of ion
[M –Alk]+ with m/z 170 (A4) consisting in a migration of
a group of atoms to the cationic site [15], in this event of
a methyl group to the O-centered cation providing an
open-chain ion A5 that further ejects radical NCS [16].
Obviously this process may occur in the fragmentation
of [M]+· of all studied 3-alkoxydihydroazepines and
therefore to make certain or prevailing contribution into
the intensity of peaks of ions [M – MeSCN]+· (for
methoxy analogs II, IIIa, IV, and V) and N (for
compounds IIIc and IIId) (Tables 1 and 2).
In general, the mass spectra of 3-alkoxy-4,5-dihydro-
3H-azepines IIIb–IIId (Alk > Me) contain three series
of ions corresponding to ether fragmentation type of the
proper compounds IIIb–IIId and to sulfide fragmentation
type of the odd-electron ions formed therefrom with m/z
171 and 153, namely, of the molecular ions of 4,5-dihydro-
3H-azepin-3-ol (VIII) (Scheme 6) and 2-methyl-7-
(methylsulfanyl)-3H-azepine (XII) (Scheme 11).
Introducing into the position 3 of 4,5-dihydro-3H-aze-
pine of a phenyl and a pyrrole ring changes the character
of the molecular ion fragmentation. The peak of ion
[M–MeSCN]+· and/or of [A1–NCS]+· (C), the diagnostic
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

MASS SPECTRA OF NEW HETEROCYCLES: VII.
299
ion for the fragmentation of 3-methoxy-substituted 4,5-
dihydro-3H-azepines, and also peaks of a number of other
ions characteristic of the fragmentation [M]+· of
compounds II–V are lacking in the spectra of 3-phenyl-
4,5-dihydro-3H-azepine (VI) and 3-(pyrrol-1-yl)-4,5-
dihydro-3H-azepine (VII). The probable routes of
formation, m/z values, relative intensities, and the
structures of the main fragment ions of compounds VI
and VII are presented in Schemes 8 and 9.
Alongside the main ion [M – MeS]+ in the spectrum
of dihydroazepine VI two more ions are present
corresponding to the primary fragmentation of [M]+·.
These are ions [M – Me]+ (A1) and [M – C2H4]+· (R).
The latter fragmentation channel of the molecular ion
involving synchronous or successive rupture of C3–C4
and C5–C6 bonds and the formation of a molecule of 2H-
or 3H-pyrrole was not previously observed in the series
of the studied 4,5-dihydro-3H-azepines. Evidently the
phenyl substituent destabilized the dihydroazepine ring.
The same is confirmed by the relatively low intensity of
the molecular ion of dihydroazepine VI and, on the
contrary, the maximum intensity of the ion peak with m/
z 184 formed by the elimination of MeS radical followed
by the rearrangement of the primary ion involving the
phenyl group. The likely driving force of this rearrange-
ment of ion [M – MeS]+ is the formation of a stable
tricyclic fused system: ions of 2-methyl-4,4-dihydro-3H-
benzo[3,4]cyclobuta[1,2-b]azepinium B2 or 2-methyl-4,9-
dihydro-3H-indeno[2,1-b]pyridinium B3.
For compound VI, unlike compounds II–V, the
prevailing channel is the rupture of C2–S bond to form a
stable ion [M – MeS]+ with m/z 184 (100%) (B2 or B3).
Its further fragmentation occurs both along channels
characteristic of compounds II, IIIa, IV, and V
(formation of ions K1 [B2 – MeCN]+ and L1 [K1 –
C2H2]+) and via new fragmentation channels (Scheme
8). The channels belonging to the latter are the ejection
by ion B2 of hydrogen and 2,3-dihydroazete molecules,
and also of 2,3-dihydroazetium cation leading to the
formation of ions O, P, and Q with m/z 182, 129, and 128
respectively. The successive ejection by ion O of
molecules MeCN and C2H2 results in ions with m/z 141
(23%) and 115 (50%).
Unlike 3-phenyl-4,5-dihydro-3H-azepine (VI) 3-(pyr-
rol-1-yl)-4,5-dihydro-3H-azepine (VII) formed a max-
imum stable molecular ion (peak intensity 100%). In the
Scheme 8.
+.
+.
Ph
SMe
Ph
SMe
+.
Me
Me
N
N
Ph
Ph
[C9H7S]+
_C2H4
+
_C2H4,
_MeCN
_Me.
N
N
Me
SMe
Me
S
S, m/z 147 (20)
H
VI, M+., m/z 231 (16)
A1, m/z 216 (27)
_SMe.
R, m/z 203 (12)
_H2
+
+
+
Me
.
N
N
N
H
H
Me
Me
H
B3
B2, m/z 184 (100)
O, m/z 182 (24)
_C3H6N
_MeCN
_C3H5N
_MeCN
[C9H9]+
[C11H11]+
[C10H9]+
[C10H8]+.
Q, m/z 128 (17)
[C11H9]+
_C2H2
L1, m/z 117 (37)
P, m/z 129 (19)
K1, m/z 143 (10)
m/z 141 (23)
_C2H2
[C9H7]+
m/z 115 (50)
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KLYBA et al.
300
hetaryl-substituted 4,5-dihydro-3H-azepine VII no frag-
mentation occurs leading to the formation of ions [M –
MeS]+ and [M – C2H4]+·. The only channel of the primary
fragmentation of the molecular ion is here the ejection of
a methyl radical. Besides the possibility to stabilize the
primary fragment ion [M – Me]+ with m/z 205 by localiza-
tion of the positive charge on the nitrogen of the pyrrole
ring (A6) completely changes the character of its
fragmentation (Scheme 9).
Further fragmentation of ion [M – Me]+ takes two
new, previously unknown routes (with the elimination of
MeCNH and SH radicals) and results in odd-electron
ions with m/z 163 (45%) and 172 (10%) that presumably
has structures respectively of 1-(4H-thiopyran-3-yl)-1H-
pyrrole (IX) and 2-methyl-6-(1H-pyrrol-1-yl)-4H-azepine
(X) (or its isomers). Structure IX is confirmed by its
subsequent fragmentation with the loss of sulfur-
containing radicals HCS, C2H3S, and C4H5S. The
fragmentation of ion with m/z 172 (azepine X), on the
contrary, involves the ejection of neutral species HCN,
MeCN, and C2H4.
In the course of spectral monitoring of 4,5-dihydro-
3H-azepines II and IIIa–IIId using a system of
chromatographically introducing samples into the ion
source we discovered a new thermally induced reaction
of alkanol elimination leading to the formation of
previously unknown 7-(methylsulfanyl)-3H-azepines XI
and XII (Scheme 10).
It turned out that at the chromatographical introduction
of samples (vaporizer and ion source temperature 120–
180°C, pressure 100–150 kPa) on the chromatograms
alongside the peak of the analyzed compound II or IIIa
were registered peaks of its structural isomer and of one
more substance whose mass spectrum corresponded to
7-(methylsulfanyl)-3H-azepine (XI or XII respectively)
or its isomers (Schemes 10 and 11). At 250°C and the
pressure 150 kPa the samples IIIb–IIId also suffered
thermal decomposition with alkanol elimination and the
formation of 3H-azepine XII. In the chemical experiment
we failed to observe this reaction route (although did not
exclude it). The thermal elimination of methanethiol with
the formation of 6-alkoxy-3H-azepines XIII did not occur
Scheme 9.
+.
+.
HCN + m/z 145 (17)
N
N
C2H4 + m/z 144 (7)
N
N
Me
Me
Me
SMe
MeCN + m/z 131 (6)
VII, M +., m/z 220 (100)
X, m/z 172 (10)
_Me.
_SH.
+.
N
N
N+
+
_MeCNH.
S
N
N
Me
S
SH
H
IX, m/z 163 (45)
A1, m/z 205 (64)
_C2H4,
A6
HCS. + m/z 118 (7)
_MeCN
[C7H6NS]+
O1, m/z 136 (13)
C2H3S. + m/z 104 (9)
C4H5S. + m/z 78 (9)
Scheme 10.
120_250oC
(_MeSH)
180_250oC
(_AlkOH)
OAlk
OAlk
R2
R2
II, IIIa_IIId
SMe
R2
SMe
N
N
N
XI (R2 = H),
XII (R2 = Me)
XIII
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MASS SPECTRA OF NEW HETEROCYCLES: VII.
301
under these or even more rigid conditions (250°C, 100–
280 kPa). The analysis of chromatograms suggests that
the alkanol elimination occurs not from the initial 4,5-
dihydro-3H-azepines, but from their structural isomers
forming only under the chromatographic conditions and
having indentical mass spectra.
In 3-alkoxy-4,5-dihydro-3H-azepines IIIb–IIId where
Alk > Me the fragmentation of the molecular ion follows
the rules characteristic of alkyl ethers. Beside the simple
rupture of C–O bond to obtain ions [Alk]+ and [M –Alk]+
here also cleavage occurs of carbon–oxygen bonds with
simultaneous hydrogen transfer, in particular, the ejection
from [M]+· of alkene molecule (from the alkoxy
substituent), and also of alkanol with the formation of
odd-electron ions [M – CnH2n]+· and [M – AlkOH]+· cor-
responding to the structures of 7-methyl-2-(methylsulfan-
yl)-4,5-dihydro-3H-azepin-3-ol (VIII) and 2-methyl-7-
(methylsulfanyl)-3H-azepine (XII) respectively. Further
fragmentation of the arising cation-radicals might
contribute certain “distortions” into the overall pattern of
fragmentation of the molecular ions of compounds IIIb–
IIId. 7-(Methyl-sulfanyl)-3H-azepines XI and XII formed
also by thermal decomposition of compounds II and IIIa–
IIId respectively during the registering of mass spectra.
It should be noted that the products of simple elimination
of hydrogen or alkyl radicals from the α-position
(α-cleavage is usually the prevailing process in ethers
decomposition) were not identified in the spectra of
3-alkoxy-4,5-dihydro-3H-azepines IIIb–IIId.
It was established that at electronic ionization 3H-
azepines XI and XII formed stable molecular ions whose
primary fragmentation in both compounds involved the
elimination of methylsulfanyl group or its fragments to
give ions [M – MeS]+, [M – CH2S]+·, [M – SH]+, and [M –
Me]+ (Scheme 11). Further fragmentation of the latter
involves the elimination of R2CN, C2H2, and CS species.
By the same channels occurs the fragmentation of
the odd-electron ion [M – AlkOH]+·, m/z 153, formed at
the fragmentation of molecular ions of alkoxydihydro-
azepines IIIb–IIId.
Hence it was established that the molecular ion
fragmentation of all 3-methoxy-4,5-dihydro-3H-azepines
II, IIIa, IV, and V proceeded by the same three
competing channels with the localization of the cation-
radical center on nitrogen, oxygen, or sulfur atoms giving
diagnostic ions [M – MeSCN]+· or [M – Me – NCS]+·.
Namely, the rules we had previously found for the
fragmentation of 7-methyl-2-(methylsulfanyl)-3-methoxy-
4,5-dihydro-3H-azepine (IIIa) under electronic ionization
[1] were general for all studied 3-methoxy-substituted
dihydroazepines.
Molecular ions of aryl- and hetaryl-substituted 4,5-
dihydro-3H-azepines VI and VII undergo fragmentation
mainly by the sulfide type. However here the similarity
between them ends. From 3-phenyl-4,5-dihydro-3H-
azepine (VI) form both possible ions of the sulfide frag-
Scheme 11.
+.
_C2H2
+
R2
S
_Me.
+
N
R2
SMe
R2
S
H
N
N
_R2CN
H
XI, m/z 98 (22)
XII, m/z 112 (16)
XI, M+., m/z 139 (100)
XII, M+., m/z 153 (100)
XI, m/z 124 (53)
XII, m/z 138 (8)
_CS
_SMe.
_SCH2
_SH.
+
+
S
XI, m/z 93 (26)
XII, m/z 107 (16) XII, m/z 120 (15)
XI, m/z 106 (14)
R2
N
XI, m/z 92 (30)
XII, m/z 106 (17)
H
m/z 97:
XI (44), XII (70)
XI, m/z 80 (24)
XII, m/z 94 (11)
_R2CN
_R2CN
_R2CN
_S
_R2CN
m/z 65:
m/z 66:
m/z 79:
[C5H5]+
m/z 65:
[C4H5]+
m/z 53:
XI (47), XII (49)
XI (10), XII (14) XI (4), XII (22)
XI (47), XII (49)
XI (19), XII (20)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009

KLYBA et al.
302
mentation, [M – Me]+ and [M – MeS]+, and the latter
prevails. This ion has a maximum intensity (100%) and
a probable structure of 2-methyl-4,4-dihydro-3H-benzo-
[3,4]cyclobuta[1,2-b]azepinium or 2-methyl-4,9-dihydro-
3H-indeno[2,1-b]pyridinium. Besides in this case operates
a quite new third fragmentation channel of the molecular
ion: ejection of the ethylene molecule to form an odd-
electron ion corresponding to the structure of 2H- or 3H-
pyrrole.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
05-03-32578a).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 2 2009