Structure of the product of interaction of n-vinylcaprolactam with 3-chlorophenylisocyanate

Article abstract of DOI:10.1134/S0022476611010240

The [2+2]-cycloaddition reaction of N-vinylcaprolactam with 3-chlorophenylcyanate yielding 1-(3- chlorophenyl)-4-[1H-perhydroazepinone-2]- azetidinone-2 is studied. The structure of the obtained compound is determined by single crystal XRD.

Full text of DOI:10.1134/S0022476611010240

Journal of Structural Chemistry. Vol. 52, No. 1, pp. 180-185, 2011
Original Russian Text Copyright © 2011 by A. R. Zaripova, R. R. Spiridonova,
O. I. Gnezdilov, I. Kh. Rizvanov, I. A. Litvinov, A. T. Gubaydulin, and Ya. D. Samuilov
STRUCTURE OF THE PRODUCT OF INTERACTION OF
N-VINYLCAPROLACTAM WITH 3-CHLOROPHENYLISOCYANATE
1 1
A. R. Zaripova, R. R. Spiridonova, O. I. Gnezdilov,
2
UDC 547.466.3-318:546.268.2
©
3
I. Kh. Rizvanov, I. A. Litvinov, A. T. Gubaydulin,
3
3
1
and Ya. D. Samuilov
The [2+2]-cycloaddition reaction of N-vinylcaprolactam with 3-chlorophenylcyanate yielding 1-(3-
chlorophenyl)-4-[1Н-perhydroazepinone-2]-azetidinone-2 is studied. The structure of the obtained
compound is determined by single crystal XRD.
Keywords: N-vinylcaprolactam, 3-chlorophenylisocyanate, chromato-mass spectrometry analysis, single
crystal X-ray diffraction.
INTRODUCTION
We have previously shown that N-alkylated lactams, in particular, N-methylpyrrolidone [1], interact with
isocyanates to form complex compounds of isocyanurates with lactams. Possible reactions of N-vinyl-substituted lactams
with isocyanates have not yet been studied. The purpose of this paper is to investigate the interaction of N-vinylcaprolactam
with 3-chlorophenylisocyanate and determine the structure of the obtained compound.
EXPERIMENTAL
In this study, we used reagents I and III (Sigma Aldrich); the content of the basic compound was 99%. Freshly
distilled samples of compound I, triethylamine, and solvents were used in the syntheses.
The reaction of compound III with I was conducted in the argon atmosphere in vacuum-sealed ampoules. First,
5.77 ml (0.0543 mol) of toluene and 6.93 ml (0.0512 mol) of reagent III were placed in the ampoules. Then, to the obtained
–2
solution we added a catalytic amount of triethylamine (the catalyst concentration was varied from 0 to 1.35⋅10 mol/l). After
that, we introduced into the mixture an equimolar, with respect to III, amount of reagent I: 6.20 ml (0.0512 mol). The
synthesis was conducted at 70°C for 70 h. During the reaction the formation of the solid phase was observed. The resulting
precipitate was filtered off. It was dissolved in acetone to remove reagent admixtures, and the reaction products were
precipitated by hexane. The resulting product was dried in vacuum at 30°C to a constant weight.
1
The structure of the resulting products was determined by elemental analysis, IR, Н NMR spectroscopy,
gaschromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-mass spectrometry (HPLC-
MS), single crystal and powder XRD.
1
2
Kazan State Technological University; arzaripova@mail.ru, aliazari@rambler.ru. E. K. Zavoisky Physical
3
Technical Institute, Kazan Scientific Center, Russian Academy of Sciences, Kazan. A. E. Arbuzov Institute of Organic and
Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan. Translated from Zhurnal Strukturnoi
Khimii, Vol. 52, No. 1, pp. 184-489, January-February, 2011. Original article submitted March 18, 2010; revision June 2, 2010.
180
0022-4766/11/5201-0180

The elemental analysis of the samples was performed on a CHN-3 analyzer. The IR spectra were measured on a
Spectrum BX II IR Fourier spectrometer (Perkin Elmer lnc.). The samples were deposited between KBr glasses.
1
The Н NMR spectra were recorded on a Вruker AVANCE spectrometer with the working frequency of 400 MHz.
The 90°-pulse was 0.5 µs. The relaxation delay was 10 s. The number of scans was 16 or 32. Dimethylsulfoxide-d was used
6
as a solvent.
1
The following compounds were identified. Compound II: T . 223°С; Н NMR: δ, ppm: 7.41-7.55 (12Н, arom.
m
1
protons); found, %: С 55.46, Н 2.57, and N 9.30. Calculated, %: С 55.59, Н 2.56, and N 8.95. Compound IV: T 132°С; Н
m
NMR: δ, ppm: 1.17 m (2Н, СН ), 1.45 m (2Н, СН ), 1.56 m (2Н, СН ), 2.53 m (2Н, СН С(О)), 3.08 dd (1Н, СН ), 3.27 m
2 2 2 2 2
(2Н, NСН ), 3.38 dd (1Н, СН ), 6.52 dd (1Н, СН), 7.1-7.4 m (4Н, arom. protons); found, %: С 61.45, Н 5.83, and N 9.74.
2 2
Calcualted, %: С 61.54, Н 5.81, and N 9.57.
The HPLC-MS analysis was performed on an Agilent 6210 TOF mass spectrometer (dopant KI). Ionization was
performed in the positive mode. The analysis conditions were as follows: the gas flow delivery rate 5 ml/min; temperature
150°C; time of analysis of 100 s to 3200 s; and solvent МеОН+Н О.
2
The GC-MS analysis was performed on a DFS spectrometer (Thermo Fisher Electron Corporation). The
chromatography conditions were as follows: the injector temperature 280°C; flow rate 1 ml/min; split flow 1:20; helium
carrier gas; DB-MS capillary column. The initial temperature of the oven was 120°C; the heating rate was 10 deg/min. The
final temperature of the oven was 280°C. The conditions of mass spectra measurements: electron ionization; ionizing voltage
+
70 V; mass range 50-500 Da. The electron ionization mass spectra of the single crystals of IV, m/z (I , %): М 292 (18), 266
rel.
(2), 153 (11), and 140 (100).
–3
Single crystals of the product of the interaction between compounds III and I at 2.71⋅10 mol/l of triethylamine
were obtained from an acetone solution of the compound on slow evaporation of the solvent. The single crystal XRD analysis
was performed on an automatic Bruker Smart Apex II diffractometer with a two-dimensional CCD detector. The crystals of
C H ClN O (IV) are triclinic; P-1 space group; at 23°C: а = 8.648(2) Å, b = 9.061(2) Å, c = 10.229(3) Å, α = 75.939(3)°,
15 17
2
2
3 3
β = 68.574(3)°, γ = 89.303(3)°, V = 721.2(3) Å , М = 292.76, d = 1.348 g/cm , Z = 2. The cell parameters and intensities of
x
10 049 reflections, including 3408 independent reflections, 3095 of which had I ≥ 2σ (R = 0.018), were measured at a
int
temperature of 23°C (λМоK , graphite monochromator, λ = 0.71073 Å, ϕ and ω scan mode, 2.21 ≤ θ ≤ 28.48°, index area:
α
–11 ≤ h ≤ 11, –12 ≤ k ≤ 11, –13 ≤ l ≤ 13). Absorption was introduced semiempirically using the SADABS program [2]
–1
(μMoK = 2.68 cm ). The structure was solved by the direct method and refined first in an isotropic and then anisotropic
α
approximation using the SHELXL-97 [3] and WinGX [4] programs. The hydrogen atoms were found from the difference
Fourier maps and refined isotropically. The final divergence factors are R = 0.0362 and R = 0.0951 from 3095 reflections
w
2
with F ≥ 4σ; the GOOF parameter is 1.024; 250 refined parameters. Data collection, unit cell parameters, indexation and
refinement were performed using the APEX2 software [5]. The unit cell parameters, coordinates of the atoms and their
temperature parameters have been deposited with the Cambridge Crystallographic Data Centre (http://www.ccdc.cam.ac.uk)
under no. CCDC 763965. The analysis of the intermolecular interactions and the figures were made using the PLATON
program [6].
The powder diffraction patterns were measured on an automatic Bruker D8 Advance diffractometer equipped with
Vario attachment and Vantec linear PSD. The used CuK radiation (40 kV, 40 mA) was monochromated by a curved
α
Johanson germanium monochromator. The experiments were performed at a temperature of 23°C in the Bragg–Brentano
geometry with a flat-plate sample. The compound was preliminarily pressed and prepared in the form of a thin pellet (2-
4 mm) on a glass plate, then placed into a standard sample holder that was rotated (15 rpm) throughout the data collection.
The diffraction patterns were recorded in the 2θ range of 4° to 70°; step 0.0081°; step time 0.5 s. We obtained several
diffraction patterns for each sample in different experimental modes and different step times. For compound IV, whose
structure was determined by single crystal XRD, we also calculated a theoretical powder diffraction pattern. A comparison of
the latter to the experimental diffraction patterns allowed us to identify the compound.
181

RESULTS AND DISCUSSION
First, we studied the reactivity of the individual compounds under the interaction conditions. We found that in the
presence of catalytic amounts of triethylamine at 70°C for 70 h in the toluene medium, N-vinylcaprolactam does not undergo
any changes. Under these conditions, 3-chlorophenylisocyanate I forms 1,3,5-tri(3-chlorophenyl)isocyanurate II
TABLE 1. Ratio of the Absorption Band Intensity of the Isocyanate Group to the Absorption Band
Intensity of the СН Group in the Lactam Cycle of Compound III in the IR Spectra
2
Ratio of absorption band
intensities
Ratio of absorption band
intensities
Synthesis time, h
Synthesis time, h
25
0.06
1
5
1.25
0.97
0.66
40
70
0
0
10
1
The structure of compound II was confirmed by the analysis of the IR and Н NMR spectra and the elemental
analysis results.
During the reactions of N-vinylcaprolactam with I, a solid phase formed both in the presence and absence of
triethylamine. This solid precipitate was dissolved in acetone. The reaction product was precipitated by hexane to yield
yellow powder products dissolvable in acetone, toluene, chloroform, dimethylformamide, dimethylsulfoxide, acetonitrile, and
hot carbon tetrachloride. The yield of the synthesized compounds was approximately 70%.
IR spectroscopy shows that the synthesized compounds have the same structure. The IR spectra of the products
–1 –1
exhibit absorption bands in the region of 1600 cm to 1500 cm , which indicate the presence of a benzene ring. The
–1 –1
absorption bands at 2850 cm and above 3000 cm belong to the stretching vibrations of СН groups. The absorption bands
2
–1
observed in the 1800-1600 cm region correspond to the terminal vinyl group and the С=О group of N-substituted lactam.
–1
The absorption band at 2275-2250 cm that belongs to the vibrations of the isocyanate group is absent in the IR spectra. The
disappearance of the isocyanate groups was analyzed by IR spectroscopy in the reaction of N-vinylcaprolactam with
–2
compound I at 70°С in the presence of 1.35⋅10 mol/l of triethylamine. A comparison of the IR spectra reveals that the
–1
intensity of the absorption band in the 2262-2263 cm region gradually decreases, which characterizes the antisymmetric
stretching vibrations of the N=C=О group; it completely disappears with increasing reaction time (Table 1).
To determine the structure of the obtained compounds, we analyzed them by HPLC-MS with accurate mass
identification.
The analysis of the mass spectra of the products (Table 2) showed that N-vinylcaprolactam III interacts with
isocyanate I to form a compound with М 292.1006. A substance with this molecular mass corresponds to 1-(3-chlorophenyl)-
4-[1Н-perhydroazepinone-2]-azetidinone-2 IV
182

TABLE 2. Molecular Masses of the Compounds Identified by Chromato-Mass Spectrometry with the Use
of HELC in the Interaction of Compound III with Compound I
Molecular mass
Compound
Ion
experimental
theoretical
+
+
III
IV
[M + K]
[M + K]
178,.0640
331.0638
178.0634
331.0610
Fig. 1. Geometry of the molecule of
compound IV in the crystal and the
atom numbering scheme. Selected bond
lengths in the molecule: N9–C8
1.483(1) Å, C8–C11 1.552(2) Å, С13–
N9 1.399(1) Å, C10–N9 1.381(2) Å,
C10–C11
1.448(1) Å, N1–C2 1.362(1) Å, N1–C7
1.468(2) Å.
1.526(2) Å,
N1–C8
–3
To refine the structure of compound IV, we grew its single crystals (using 2.71⋅10 mol/l triethylamine) and
performed single crystal XRD measurements. The study shows that synthesized compound IV crystallizes individually with
one independent molecule in the asymmetric part of the triclinic unit cell. The geometry of the molecule is shown in Fig. 1. In
the molecule of IV, the β-lactam ring is planar within the experimental error of 0.0032(2) Å, and the seven-membered
caprolactam cycle in the chair conformation is orthogonal to the plane of the four-membered cycle.
The chlorophenyl substituent is rotated about the N9–C13 bond from the four-membered ring plane: the dihedral
angle between its planes is 6.0°. This position of the substituent is likely to be stabilized by the intramolecular С–Н…О type
hydrogen bond observed in the crystal between О10 oxygen of the carbonyl group and the Н14 hydrogen atom of the
chlorophenyl substituent (d(O10…H14) 2.49 Å, ∠(O10…H14–C14) 122°). The position of the caprolactam cycle appears to
be stabilized by the C–Н…N type interaction between the N9 nitrogen atom of the β-lactam ring and the Н71 hydrogen atom
of the methylene group of caprolactam (d(N9…H71) 2.48 Å, ∠(N9…H71–C7) 110°). Moreover, the crystal structure of
compound IV is observed to have intermolecular С–H…O type interactions. The total effect of the С–Н…О interactions
results in the formation of Н-bonded molecule layers in the crystal, which are parallel to the 101 crystallographic plane
(Fig. 2а). The parameters of these interactions are fairly close: the H…O distances are in the range of 2.44 Å to 2.60 Å, and
the C–H…O angle is within 131-159°.
183

Fig. 2. Two projections of the layers of Н-bonded
molecules of compound IV in the crystal: (a) view
along the b crystallographic axis; (b) view along the a
axis. The С–H…O hydrogen bonds are shown by
dashed lines.
These supramolecular layered structures are linked with one another through π…π contacts between the π systems
of chlorophenyl substituents of two molecules from the neighboring layers bound by the symmetry center. This results in the
formation of a three-dimensional network of molecules. In two directions, this network is formed by С–Н…О interactions,
and in the third one, by π electron interactions (the distance between the cycle centers is 3.74 Å; the dihedral angle is 0°; the
shortest distance between the planes is 3.45 Å; and the symmetry operation is (1 – x, 1 – y, 1 – z)). Such a molecular packing
leads to the absence of free volumes in the crystal, which can be potentially accessible for solvent molecules, and in fairly
dense crystal packing: the calculated packing coefficient of 68.3% proves to be in the middle of the range (0.65-0.75) typical
of the crystals of organic compounds.
From the single crystal XRD data (atom coordinates and cell parameters), we calculated a theoretical powder
diffraction pattern for compound IV. We also calculated a theoretical powder diffraction pattern for compound III, whose
crystallographic data were found in the Cambridge Crystallographic Data Centre (Refcod — NUQYED) [7]. The theoretical
diffraction patterns were compared to the experimental diffraction patterns of the products synthesized in the presence or
absence of triethylamine (Fig. 3).
This figure shows that the theoretical diffraction pattern for compound IV (Fig. 3, curve 5) coincides with the
experimental diffraction patterns obtained for the products synthesized by the interaction of compound III with I at the
–3
triethylamine concentration of 0 and 1.35⋅10 mol/l (Fig. 3, curves 1 and 2 respectively). However, they are observed to
differ from the experimental diffraction pattern of the products synthesized in the presence of triethylamine in the amount of
–3
–2
2.71⋅10 mol/l and 1.35⋅10 mol/l (Fig. 3, curves 3 and 4 respectively). These experimental diffraction patterns have
additional interferential peaks that correspond, as shown by a comparison of these patterns to the theoretical pattern for
compound III (Fig. 3, curve 6), to the crystalline phase of this compound. At the same time, the content of compound III in
the reaction products increases with increasing triethylamine concentration in the reaction mixture. This fact is also
confirmed by a comparison of the peak intensities in the chromatograms obtained by HELC-MS for the respective
184

Fig. 3. Fragments of the diffraction patterns for the products of interaction of compound III with I at
–3 –3
the triethylamine concentration: (1) 0 mol/l, (2) 1.35⋅10 mol/l, (3) 2.71⋅10 mol/l, (4) 1.35⋅
–2
10 mol/l, (5) theoretical diffraction pattern for IV, and (6) theoretical diffraction pattern for III.
TABLE 3. Ratio of the Peak Intensity for Compound IV to Peak Intensity for Compound III in the Chromatogram
Concentration of triethylamine in the reaction feed, mol/l
Ratio of peak intensities
0
843
79
–2
1.35⋅10
–2
compounds in the reaction products synthesized in the absence of triethylamine and its concentration of 1.35⋅10 mol/l in the
reaction mixture (Table 3).
The results of this research show that triethylamine inhibits the reaction under study.
Thus, it is shown the the [2+2]-cycloaddition reaction of N-vinylcaprolactam with 3-chlorophenylisocyanate yields
1-(3-chlorophenyl)-4-[1Н-perhydroazepinone-2]-azetidinone-2. The structure of this compound contains the four-membered
β-lactam cycle that is responsible for the antibiotic activity of penicillin and cephalosporin derivatives, and a number of other
natural and synthetic antibiotics [8]. The possibility of the formation of the azetidinone cycle in the reaction of N-
vinylsubstituted lactams with cyanates is of practical interest for the production of new synthetic β-lactam antibiotics with a
wide spectrum of biological activity.
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185