Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under electron ionization and in the condensed phase

Article abstract of DOI:10.1002/rcm.7717

Rationale: Mass spectrometry is known as an excellent method to predict the behavior of organic compounds in solution. The behavior of organic compounds in the gas phase inside the ion source of a mass spectrometer allows their intrinsic properties to be defined, avoiding the influence of intermolecular interactions, counter ions and solvent effects. Methods: Arylpyrrolidin-2-ones were obtained by condensed-phase synthesis from the corresponding N-arylcyclopropanecarboxamides. Electron ionization (EI) with accurate mass measurements by high-resolution time-of-flight mass-spectrometry and quantum chemical calculations were used to understand the behavior of the molecular radical cations of N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones in the ion source of a mass spectrometer. The geometries of the molecules, transition states, and intermediates were fully optimized using DFT-PBE calculations. Results: Fragmentation schemes, ion structures, and possible mechanisms of primary isomerisation were proposed for isomeric N-arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones. Based on the fragmentation pattern of the N-arylcyclopropanecarboxamides, isomerisation of the original M^+? ions into the M^+? ions of the N-arylpyrrolidin-2-ones was shown to be only a minor process. In contrast, this cyclization proceeds easily in the condensed phase in the presence of Br?nsted acids. Conclusions: Based on the experimental data and quantum chemical calculations the principal mechanism of decomposition of the molecular ions of N-arylcyclopropanecarboxamides involves their direct fragmentation without any rearrangements. An alternative mechanism is responsible for the isomerisation of a small portion of the higher energy molecular ions into the corresponding N-arylpyrrolidin-2-one ions. Copyright

Full text of DOI:10.1002/rcm.7717

Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidinones-2
under electron ionization and in the condensed phase
Cyclization of N-arylcyclopropanecarboxamides under EI
A.T. Lebedev*1, D.M.Mazur1, A.I.Kudelin1, A.N.Fedotov1, I.P.Gloriozov1,
Yu.A.Ustynyuk1, V.B.Artaev2
1
Organic Chemistry Department, M.V.Lomonosov Moscow State University,
Moscow, 119991, Russia
2 LECO Corporation, 3000 Lakeview Avenue, St Joseph, MI, USA
* Address reprint request to Prof. A. T. Lebedev, Organic Chemistry
Department, M.V.Lomonosov Moscow State University, Moscow, 119991,
Russia
E-mail: a.lebedev@org.chem.msu.ru
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/rcm.7717
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RATIONALE: Mass spectrometry is known as an excellent method to predict
the behavior of organic compounds in solution. The behavior of organic
compounds in the gas-phase inside an ion source of a mass spectrometer allows
their intrinsic properties to be defined, avoiding the influence of intermolecular
interactions, counter ions and solvent effects.
METHODS: Arylpyrrolidinones-2 were obtained by condensed phase synthesis
from the corresponding N-arylcyclopropanecarboxamides. Electron ionization
(EI) with accurate mass measurements by high-resolution time-of-flight mass-
spectrometry and quantum chemical calculations were used to understand the
behavior of the molecular radical cations of N-arylcyclopropanecarboxamides
and N-arylpyrrolidinones-2 in the ion source of a mass spectrometer. The
geometries of the molecules, transition states, and intermediates were fully
optimized using DFT-PBE calculations.
RESULTS: Fragmentation schemes, ion structures, and possible mechanisms
of
primary
isomerisation
were
proposed
for
isomeric
N-
arylcyclopropanecarboxamides and N-arylpyrrolidinones-2. Based on the
fragmentation pattern of the N-arylcyclopropanecarboxamides, isomerisation of
the original M+ ions into the M+ ions of the N-arylpyrrolidinones-2 was shown
to be only a minor process. On the contrary, this cyclization proceeds easily in
the condensed phase in the presence of the Brønsted acids.
CONCLUSION: Based on the experimental data and quantum chemical
calculations the principal mechanism of decomposition of the molecular ions of
N-arylcyclopropanecarboxamides involves their direct fragmentation without
any rearrangements. An alternative mechanism is responsible for the
isomerisation of a small portion of the higher energy molecular ions into the
corresponding N-arylpyrrolidinones-2 ions.
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Keywords: N-arylcyclopropanecarboxamides, N-arylpyrrolidinones-2, electron
ionization, accurate mass measurements, isomerisation, DFT-calculations
Mass spectrometry has proven itself to be a powerful and rapid method
for the prediction of the direction and yields of monomolecular reactions of
[1-4]
organic compounds in solution.
The study of the behavior of organic
compounds in the gas phase in the ion source of a mass spectrometer allows
their intrinsic properties to be defined, thus avoiding the influence of
[4]
intermolecular interactions, counter ions and solvent effects. Comparison of
the results of the reaction taking place in the gas and condensed phases may be
very important in revealing the effects of solvent and counter ions. These issues
[5]
are also relevant for the study of gas-phase ion-molecule reactions. The vast
majority of the classic organic chemistry rearrangements have been shown to
take place in the ion source of a mass spectrometer in both polarities. [4, 6, 7]
We previously successfully used mass spectrometry to study the
transformations of various ortho-substituted phenylcyclopropanes as well as
[4]
[8]
diazo compounds in both positive
and negative
ion modes, mimicking
reactions catalyzed by acids and bases in solution. The spectra obtained for
several series of ortho-substituted cyclopropylbenzenes were used to confirm
the presence of the predicted heterocycles in solution. The cyclization products
of the molecular ions for these arylcyclopropanes were identical to those
synthesized in the condensed phase. [9-12]
In the present study we continue research in this area investigating the
possibility of rearrangements of substituted N-arylcyclopropanecarboxamides
(1a-l) into N-arylpyrrolidones-2 (2a-l) (Scheme 1). This reaction is known to
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proceed in the condensed phase. [13, 14] Compounds 1 were expected to undergo
EI-induced cyclization in a similar manner.
H
N
N
R
R
O
O
1a-l
2a-l
Scheme 1.a) R=H, b) R = o-CH3, c) R = p-CH3, d) R = o-C2H5, e) R = p-C2H5,
f) R = o-F, g) R = o-Cl, h) R = p-Cl, i) R = p-Br, j) R = p-I, k) R = o-OC2H5,
l) R = p-NO2
Experimental
Synthesis of substituted N-arylcyclopropanecarboxamides (1)
These compounds were synthesized using the Schotten-Baumann reaction. [15]
A
solution of cyclopropanecarbonyl chloride (1.05 g, 10 mM) in dichloromethane
(10 mL) was added dropwise to the mixture of the corresponding substituted
aniline (10 mM) and triethylamine (1.11 g, 11 mM) in dichloromethane (40 mL)
with continuous stirring over a period of 1 hr at room temperature. After 5 hrs
the reaction mixture was poured into 100 mL of ice water. The organic phase
was washed 3 times with water (100 mL) and dried over anhydrous MgSO4.
After solvent evaporation the targeted N-arylcyclopropanecarboxamides 1 were
purified by recrystallization from a mixture of MeOH and H2O (1:1). The purity
of the reaction products was checked by NMR and GC/MS. The spectral data
are presented in the Supplementary Information.
Synthesis of substituted N-phenylpyrrolidones-2 (2)
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The synthesis of N-arylpyrrolidones-2 from N-arylcyclopropane-
[13]
carboxamides was successfully achieved earlier.
The reaction proceeds in
the presence of tetrabromomethane and triphenylphosphine. The same reaction
was carried out at the Chemistry Department of Moscow State University
(Moscow, Russia) in considerably milder conditions without using any
halogenated or phosphorus-containing reagents. Thus, the suggested method
could actually satisfy the concept of “green” chemistry. The rearrangement of
compounds 1 into 2 was carried out at an elevated temperature (about 190–230
ºC). Since the use of any solvent at these temperatures becomes problematic, we
employed condensed phase synthesis with NH4I, as a protonating agent. At this
elevated temperature ammonium iodide undergoes partial sublimation, existing
in equilibrium with ammonia and hydrogen iodide. The latter species may
protonate reagent 1 molecules.
A powder of 0.244 g (2.4mM) aluminum oxide (II grade activity) was
thoroughly mixed and ground with a spatula in a silica vial with 0.128 g
(0.88mM) of powdered NH4I and 0.8 mM of amides 1. The mixture was heated
in a Monowave 300 microwave oven (Anton Paar, Ostfildern-Scharnhausen,
Germany) for 30 min at 200 ºC. The reaction products (Scheme 1) were
extracted with chloroform (5 mL x 3), concentrated at reduced pressure and
purified by column chromatography. The yields of the pyrrolidines 2 are in the
wide range between 20% and 80%, depending on the substituents in the
aromatic ring. The EI mass spectra of N-arylcyclopropanecarboxamides 1 and
N-arylpyrrolidones-2 (2) are summarized in the Supplementary Information.
Mass Spectrometry
All experiments were performed with a Pegasus GC-HRT time-of-flight
(TOF) high-resolution mass-spectrometer (LECO Corporation, Saint Joseph,
MI, USA) with Folded Flight Path multiple reflecting geometry coupled with an
Agilent 7890A Gas Chromatograph (Agilent, Palo Alto, CA, USA). The system
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was controlled by ChromaTOF-HRT software, version 1.80 (LECO
Corporation), which was also used for data collection and data processing. The
data were collected using 10 full (m/z 10-500 range) spectra per second in high-
resolution mode (25,000 at FWHH), reliably determining the elemental
composition of all the ions. Multi-point mass calibration on FC-43 (PFTBA)
mass spectra was performed before running the samples as a part of the
automated tuning routine. The mass spectrometer hardware and acquisition
software allow mass drift during data collection to be minimized. The electron
ionization source was kept at 250°C, while the electron energy was 70 eV.
Chromatographic separation was performed using a Rxi - 5Sil M 30m length
column, of internal diameter 250 mm and phase thickness 0.25μm. The carrier
gas was helium at a flow rate of 1 mL min-1; the column temperature was
programmed as follows: 50°C (2 min) then ramped at 10°C/ min to 280°C; and
the transfer line temperature was 320°C. 1 mL of dichloromethane solution was
introduced into the injector heated at 280°C at a split ratio of 50:1.
NMR spectra
1H NMR spectra of compounds 1 and 2 were recorded with Avance-400
spectrometer (Bruker BioSpin, Rheinstetten, Germany) in CDCl3 and (CD3)2CO
solution (400 MHz) using tetramethylsilane (TMS) as an internal standard. The
spectra were used exclusively to confirm the structures of compounds 1 and 2.
Computational Details
The geometries of molecules, transition states, and intermediates were
fully optimized using DFT-PBE calculations. The full electron TZ basis set L2
was used. The numbers of contracted and primitive functions used in L2 were,
[16]
respectively, {3,2,1}/{8,4,2} for H, {4,3,2,1}/{12,8,4,2} for C, N, and O.
Stationary points on the potential energy surface were identified by analyzing
Hessians. The thermodynamic functions (Gibbs energies, G) at 298.15 K were
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calculated using an approximation of rigid rotator and harmonic oscillator.
[17]
Atomic charges were calculated according to Hirschfeld.
were found by the intrinsic reaction coordinate method.
Reaction paths
All calculations
[18]
were performed using the MBC100k cluster at the Joint Supercomputer Center
(Moscow, Russia) with the use of the PRIRODA04 program written by Laikov.
[19]
Results and discussion
Acid-catalyzed rearrangement of N-arylcyclopropanecarboxamides (1)
theoretically could result in the formation of several products including alkenes
due to cleavage of the cyclopropyl moiety or heterocyclic compounds formed as
a result of ortho-substitution in the aromatic ring. [9-12] However, in all the cases
condensed phase transformation of 1 yielded a single product 2, while some
portion of the original reagent remained unreacted. Figure 1 presents a TIC
chromatogram of the reaction mixture of ortho-chlorinated cyclopropane 1c
after 6 hrs of heating at 200 ºC with NH4I. There are only 2 peaks: the first
belongs to the initial compound 1c and the second to the targeted pyrrolidone
2c.
1.0e7
8.0e6
6.0e6
4.0e6
2.0e6
0.0e0
Time (s)
450
500
550
TIC
600
650
700
Fig.1. Total ion chromatogram of the reaction mixture of ortho-chlorinated
cyclopropane 1c
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The electron ionization spectra of isomers 1 and 2 appeared to be very
different from one another. Figures 2a and 2b present these spectra for the
unsubstituted compounds 1a and 2a, respectively.
Fig. 2a. EI spectrum of N-arylcyclopropanecarboxamide (1a)
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Fig. 2b. EI spectrum of N-phenylpyrrolidone-2 (2a)
The molecular ion peaks are quite pronounced in all the spectra which is a
typical feature of aromatic compounds.[20] The base peak in the spectra of N-
arylcyclopropanecarboxamides 1 is always due to the ion with the structure of
the molecular ion of the substituted aniline (m/z 93 in Fig. 2a) formed as a result
of N-C(O) bond cleavage accompanied by a hydrogen shift. This process is
typical for N-phenylalkylamides and involves the charged site triggering a four-
membered transition state.[20] The hydride-anion migrates from the CH-group of
the cyclopropyl moiety. The process is accompanied by the loss of the
cyclopropylketene molecule. Alternatively, the charge may be retained on the
complementary ion of m/z 69 (Scheme 2), where it is formed by cleavage of the
same N-C(O) bond, but without hydrogen migration. The intensity of that peak
is quite pronounced in the spectra of all the N-arylcyclopropanecarboxamides 1
+
(Table 1). Another ion worth mentioning is C3H5 (m/z 41), which is formed by
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the loss of a CO molecule from m/z 69. Its intensity is quite high in the spectra
of all the N-arylcyclopropanecarboxamides 1 (Table 1).
+.
The intensity of the three mentioned peaks (ArNH2 , m/z 69, and m/z 41)
is quite low in the EI spectra of N-arylpyrrolidones-2 (Table 1). The base peak
in these spectra arises due to a loss from the molecular ion of 55 Da (CH2CHCO
radical according to the accurate mass measurements). This fragmentation
process involves the stepwise cleavage of the C-C and N-C(O) bonds of the
pyrrolidine ring. Hydrogen migration to the positively charged nitrogen atom in
the intermediate results in the formation of a stable ammonium type fragment
ion (m/z 106 in Fig. 2b). An alternative hydrogen migration from the arylamino
moiety rationalizes the loss of the CH3CH2CO radical (57 Da) with the
formation of an isonitrile-type ion (m/z 104 in Fig. 2b). The minor process
involves the losses of CO and HCO species from the molecular ions of
pyrrolidines 2. Their composition is confirmed by the accurate mass
measurements, while their structure may be cyclic (azetidines in Scheme 2) or
linear. It is worth mentioning that the [M – 57]+ ion may form stepwise through
the consecutive losses of a HCO radical and an ethylene molecule.
It is important to emphasize that two characteristic pyrrolidines 2 ions,
([M – 55]+ and [M – 57]+), are also present in the spectrum of N-
arylcyclopropane-carboxamide (Fig. 2a; m/z 104 and 106). They are also
present in the spectra of all other N-arylcyclopropanecarboxamides 1, although
their intensities are quite low. As these species definitely cannot be formed
directly from the molecular ions of N-arylcyclopropanecarboxamides,
transformation of a small portion of the latter into N-arylpyrrolidones-2 may be
proposed.
Because there are few ions in these mass spectra and the elemental
compositions of all the ions is known due to accurate mass measurements, it is
possible to propose the following general fragmentation scheme, covering both
isomeric classes of compounds (1 and 2).
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Scheme 2. The most efficient general fragmentation pathways of isomeric
compounds 1 and 2
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Table 1. The relative intensities of the characteristic ions in the EI mass spectra
of compounds 1 and 2 (% in total ion current)
Comp
1a
2a
1b
2b
1c
2c
1d
2d
1e
2e
1f
m/z 41 m/z 69 M-HCO M-CO [M–55] [M–57] [M–68] [M–84]
7.74
0.89
6.04
1.02
5.68
0.73
6.70
1.08
6.78
5.4
11.0
-
0.09
0.77
-
-
0.71
38.1
0.71
19.5
0.83
42.4
0.68
22.2
0.21
1.21
0.83
44.0
0.45
15.6
0.32
32.95
0.19
16.79
0.34
27.9
0.15
2.58
0.09
33.7
0.24
3.94
0.24
5.92
0.16
1.99
0.12
1.58
0.16
2.00
0.28
4.02
0.09
2.23
0.08
2.57
0.04
1.71
0.06
1.44
0.07
3.29
0.03
0.33
38.9
1.30
38.8
0.26
40.2
0.25
22.9
-
2.73
9.30
1.51
5.27
1.19
4.94
0.19
0.73
0.19
0.52
0.53
3.83
0.39
3.3
1.12
10.1
0.07
7.49
0.1
-
2.48
0.10
0.50
-
2.22
0.04
0.28
8.47
1.24
10.0
8.49
12.4
0.44
12.6
0.04
15.7
0.09
13.9
-
-
0.06
-
0.06
-
17.2
11.7
37.8
0.22
21.4
0.06
28.7
0.11
17.9
0.09
35.3
1.17
22.9
-
0.11
-
-
8.55
0.62
8.04
0.85
9.49
0.76
8.14
0.62
6.93
1.04
6.59
1.22
12.9
1.48
-
0.39
-
0.39
-
2f
1g
2g
1h
2h
1i
0.05
-
-
-
0.75
4.98
0.37
2.6
0.41
-
0.22
-
0.1
-
0.52
0.01
0.35
-
2i
11.2
0.54
9.91
0.53
38.0
0.98
0.28
1.59
0.12
1.02
3.23
0.21
1j
0.16
-
2j
1k
2k
1l
0.2
0.06
0.16
-
0.01
0.97
5.68
0.08
2l
The intensities of the [M – 55]+ and [M – 57]+ ions are much higher in spectra
of compounds 2. It is hardly possible to propose a mechanism of formation of
these ions directly from the molecular ions of 1. Therefore, the intensities of
these ions theoretically could be considered as a measure of the yield of the
transformation of molecular ions of 1 into 2. The following formula may then
be treated as a measure of transformation in the gas phase.
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where the numerator contains the sum of the intensities of the [M – 55]+ and [M
– 57]+ ions for compound 1 and the denominator the sum of the intensities of
the [M – 55]+ and [M – 57]+ ions for compound 2. Table 2 presents the yields
of the transformation of 1 into 2 calculated by this proposed formula.
Table 2. Calculated yields of the cyclization of molecular ions of cyclopropanes
1 into pyrrolidines 2
Compound Ri, %
2.3
3.7
2.1
21.3
11.5
2.3
2.9
1.1
1.2
1.4
3.7
0.4
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
The results shown Table 2 are difficult to rationalize on the basis of
inductive, mesomeric or steric effects. Therefore, for some reason the EI mass
spectra of the N-arylcyclopropanecarboxamides 1 cannot be used to mimic their
transformation into N-arylpyrrolidones-2 in the condensed phase. This
conclusion gives rise to the following question. Why does it not work with this
particular group of cyclopropanes, if it worked nicely with other types of
cyclopropanes? [9-12]
To answer this question we used DFT calculations. Three versions of the
transformation of 1 into 2 (Scheme 1) were calculated: i) thermal isomerisation
of the neutral molecule; 2) isomerisation catalyzed by the Brønsted acids
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(protonated molecule) mimicking the experimental condensed phase reaction;
and 3) isomerisation of the ionized molecule (radical-cation) formed in the ion
source of a mass spectrometer.
According to the calculations, isomerisation of the neutral molecule 1a
should proceed stepwise. The first stage involves the opening of the 3-
membered ring accompanied by tcleavage of the existing N-C(O) bond and
formation of a new N-C bond, leading to ketene 3 via transition state TS1 (Fig.
3).
The second step involves transformation of ketene 3 into
phenylpyrrolidone 2 through the formation of the 5-membered ring followed by
hydrogen migration from the N atom to the C4 atom (TS2, Fig. 3).
Fig. 3. The mechanism of thermal isomerisation 1 → 2.
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The Cartesian coordinates and energy parameters of all the discussed
structures are presented in the Supplementary Information. Due to the high
activation barrier (64.1 kcal/mol of the first stage) and (55.4 kcal/mol of the
second stage), one can conclude, that the reaction 1 → 2 is hardly possible even
at the elevated temperature (200º С).
Fig. 4. Two directions of protonation of N-arylcyclopropanecarboxamides 1
Protonation of cyclopropanes 1 may involve either the carbonyl oxygen
atom (cation 4) or the amide nitrogen atom (cation 5). Both ions are presented
in Fig. 4. In the gas phase the protonation of oxygen is more efficient (12.8
kcal/mol). However, in the applied experimental conditions in the condensed
phase compounds 1 are adsorbed at the acidic Lewis centers of the aluminum
oxide due to the bonding С=О:→Аl(O-)3. Thus, oxygen protonation to form
cation 4 is hampered. Isomerisation of the protonated cyclopropanes 1 was,
however, calculated for both structures 4 and 5.
According to the calculations, cleavage of the cyclopropyl moiety in
cation 4 and formation of a С3-N bond, leading to the protonated pyrrolidine
ring, require a transition state TS3 (Fig. 5) with a partially double С4-С1 bond
and a high energy barrier. The formation of oxygen-protonated pyrrolidine 6 is
energetically unfavorable, while the following proton shift from O or N atoms
to С1 cannot proceed as an intramolecular process (barriers 71 kсal/mol and 65
kсal/mol, respectively) as it is banned by symmetry. In the condensed phase
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these processes are possible as intermolecular reactions with participation of the
proton carrier-molecules. Nevertheless the above-mentioned facts clearly show
that isomerisation 1 → 2 with participation of cation 4 is hardly possible.
Fig. 5. Isomerisation of cation 4 with the opening of the small ring
Figure 6 illustrates the isomerisation of cation 5. Similarly to the
isomerisation of the neutral molecule the process in cation 5 involves the
opening of the 3-membered ring accompanied by the cleavage of the N-C(O)
bond. It is worth mentioning that the N-C(O) bond in cation 5 elongates from
1.383 Ǻ in the neutral molecule to 1.693 Ǻ, demonstrating its notable
weakening, and this results in the considerable (~30 kcal/mol) decrease of the
energy barrier in TS4. The first stage of the whole process is
thermodynamically neutral, resulting in the formation of N-protonated ketene 7.
Its cyclization via TS5 being exothermic takes place quite easily. Therefore, the
results obtained allow us to concluse that isomerisation 1 → 2 catalyzed by
Brønsted acids at elevated temperatures passes via the N-protonated cation 5.
The energy barrier of the rate-limiting stage calculated for the gas phase (35.7
kcal/mol at 2000С) makes this reaction quite possible at elevated temperatures.
Since the transition state TS4 is highly polar (calculated dipole momentum is
4.3D), a polar solvent or adsorption of the reagent may reduce the barrier even
more significantly.
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Fig.6. Isomerisation of cation 5 with the opening of the small ring.
Electron ionization of compound 1а results in formation of the odd-
electron M+∙ (9) due to the loss of an electron from the HOMO orbital.
Ionization therefore leads to certain changes in the geometry of the particle
before it starts to fragment. For example, the length of the N-C(O) bond
increases from 1.386 to 1.462 Å. The applied calculations demonstrate that the
above described mechanism of isomerisation of the closed shell species (Figs.
3-6) in the case of the radical-cation results in the decomposition of the original
molecular ion into two species via TS7 (Fig. 7). These species are ions of m/z
93 and 69 and they are the most abundant peaks in the mass spectrum of
compound 1a (Fig. 2a).
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Fig. 7. Energy parameters of the isomerisation of radical-cation 1a resulting in
fragmentation with the formation of ions of m/z 93 and 69
An alternative process involves the opening of the 3-membered ring
accompanied by simultaneous cyclization into the 5-membered pyrrolidine (Fig.
8). The energy barrier for this transformation at 2000С is 45.3 kcal/mol.
Although this value is ~20 kcal/mol higher than that leading to the
decomposition (Fig. 7), it is achievable for the species under electron ionization
[20]
due to the wide range of the internal energies of the molecular ions.
The
number of cyclizing molecules is low anyway. Therefore, the quantum chemical
calculations nicely correlate with the mass spectrometry results.
Fig.8. Energy parameters of the isomerisation of radical-cation 9 resulting in the
formation of pyrrolidone cycle
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Conclusion
The combined application of the chemical experiment in the condensed
phase, electron ionization in the gas phase, and DFT calculations allowed
reaction mechanisms to be proposed for the isomerisation of N-
arylcyclopropanecarboxamides into N-arylpyrrolidinones-2. The difference in
the behavior of the initial N-arylcyclopropanecarboxamides in conditions of
protonation and electron ionization is energy dependent. The principal
mechanism of isomerisation of the protonated species leads in the case of the
radical-cation species to fragmentation. An alternative transformation
mechanism is, however, responsible for the isomerisation of a small portion of
the higher energy molecular ions of N-arylcyclopropanecarboxamides into the
corresponding N-arylpyrrolidinones-2 structures.
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Acknowledgments
References
1. A. T. Lebedev. Mass Spectrometry of Diazo Compounds. Mass
Spectrom. Rev. 1991, 10, 91.
2. M. N.Eberlin. Triple-stage pentaquadrupole (QqQqQ) mass spectrometry
and ion/molecule reactions. Mass Spectrom. Rev. 1997, 16, 113.
3. 3a. F. Coelho, M. N. Eberlin. The bridge connecting Gas-Phase and
Solution Chemistries. Angew. Chem. Int. Ed. 2011, 50, 5261.
3b. M. N. Eberlin. Electrospray ionization mass spectrometry: a major
tool to investigate reaction mechanisms in both solution and the gas
phase. Eur. J. Mass Spectrom. 2007, 13, 19.
4. V. V. Lobodin, A. T. Lebedev. Analogies in monomolecular
transformations of organic compounds in solution and in mass
spectrometry experiments. Mass Spectrometry (Rus). 2005, 2, 91.
5. S. Gronert. Mass Spectrometric Studies of Organic Ion/Molecule
Reactions. Chem. Rev. 2001, 101, 329.
6. P. C. H. Eichinger, S. Dua, J. H. Bowie. A comparison of skeletal
rearrangement reactions of even-electron anions in solution and in the gas
phase. Int. J. Mass Spectrom. Ion Process. 1994, 133, 1.
7. S. K. Dua, R. B. Whait, M. J. Alexander, R. N. Hayes, A. T. Lebedev, P.
C. N. Eichinger, J. H. Bowie. The search for the gas-phase negative ion
pinacol rearrangement. J. Am. Chem. Soc. 1993, 115 , 5709.
8. A. T. Lebedev, V. A. Bakulev, R. N. Hayes, J. H. Bowie. Anionic
rearrangement in the gas phase. The collision‐induced dissociations of
deprotonated 2-diazo-2-cyanoacetamides. Rapid Commun. Mass
Spectrom. 1991, 5, 234.
This article is protected by copyright. All rights reserved.

9. A. T. Lebedev, T.N. Alekseeva, T.G. Kutateladze, S.S. Mochalov, Yu.S.
Shabarov, V.S. Petrosyan. The Electron Impact-Induced Cyclization of o-
Carboxy- and o-Carboxamidocyclopropylbenzenes. Org. Mass Spectrom.
1989, 24, 149.
10. A. T. Lebedev, I. V. Dianova, S. S. Mochalov, V. V. Lobodin, T. Yu.
Samguina, R. A. Gazzaeva, T. Blumenthal. Cyclization of ortho-
cyclopropylphenyl benzamides in gas and liquid phases. J. Am. Soc. Mass
Spectrom. 2001, 12, 956.
11. V. V. Lobodin, V. V. Ovcharenko, P. Chen, S. S. Mochalov, K. Pihlaja,
P. R. Jones, A. T. Lebedev. Cyclization of substituted N-(ortho-
cyclopropylphenyl) arylamides under conditions of chemical ionization
and atmospheric pressure chemical ionization. Mass Spectrometry (Rus).
2004, 1, 127.
12. A. T. Lebedev, G. Giorgi, O. A. Maloshitskaya, J. Kuchumova, T.
Samgina, P. Dem’yanov, N. Karakhanova, S. Mochalov, A. Fedotov.
Cyclization of 2-acyl- and 2-thioacyl-aminobenzylcyclopropanes in the
gas phase and solution. Eur. J. Mass Spectrom. 2009, 15, 385.
13. Y.-H. Yang, M. Shi. Ring-Expanding Reaction of Cyclopropyl Amides
with Triphenylphosphine and Carbon Tetrahalide. J. Org. Chem. 2005,
70, 8645.
14. R. Appel. Tertiary Phosphane/Tetrachloromethane, a Versatile Reagent
for Chlorination, Dehydration, and P-N Linkage. Angew. Chem. Int. Ed.
1975, 14, 801.
15. T. R. Hopkins, R. P. Neighbors, L. V. Phillips. Synthesis and Herbicidal
Activity of Small-Ring Compounds. J. Agric. Food Chem. 1967, 15, 501.
16. D. N. Laikov. A new class of atomic basis functions for accurate
electronic structure calculations of molecules. Chem. Phys. Lett. 2005,
416, 116.
This article is protected by copyright. All rights reserved.

17. F. L. Hirshfeld. Bonded-atom fragments for describing molecular charge
densities. Theoret. Chim. Acta (Berl.) 1977, 44, 129.
18. C. Gonzalez, H. B. Schlegel. Reaction path following in mass-weighted
internal coordinates. J. Phys. Chem. 1990, 94, 5523.
19. D. N. Laikov, Y. A. Ustynyuk. PRIRODA-04: a quantum-chemical
program suite. New possibilities in the study of molecular systems with
the application of parallel computing. Russ. Chem. Bull. 2005, 54, 820.
20. F. Turecek, F. W. McLafferty. Interpretation of mass spectra. 4th
Edition. University Science Books, Sausalito, USA, 1993.
This article is protected by copyright. All rights reserved.