Structure and Conformational Analysis of 5,5-Bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane

Article abstract of DOI:10.1134/S1070363219020051

The structure of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane 1 has been studied by means of ¹H and ¹³C NMR spectroscopy as well as X-ray diffraction analysis. The molecules of compound 1 exist in the chair conformation with th

Full text of DOI:10.1134/S1070363219020051

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 2, pp. 199–203. © Pleiades Publishing, Ltd., 2019.
Russian Text © Sh.Yu. Khazhiev, M.A. Khusainov, R.A. Khalikov, T.V. Tyumkina, E.S. Meshcheryakova, L.M. Khalilov, V.V. Kuznetsov, 2019, published in
Zhurnal Obshchei Khimii, 2019, Vol. 89, No. 2, pp. 197–201.
Structure and Conformational Analysis
of 5,5-Bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane
Sh. Yu. Khazhieva, M. A. Khusainova, R. A. Khalikovb, T. V. Tyumkinac,
E. S. Meshcheryakovac, L. M. Khalilovc, and V. V. Kuznetsova,d*
a Ufa State Petroleum Technological University, Ufa, Russia
*e-mail: kuzmaggy@mail.ru
b Bashkirian State Medical University, Ufa, Russia
c Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, Russia
d Ufa State Aviation Technical University, ul. K. Marksa 12, Ufa, 450008 Russia
Received July 26, 2018; revised July 26, 2018; accepted August 2, 2018
Abstract—The structure of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane 1 has been studied by means
1
of Н and 13С NMR spectroscopy as well as X-ray diffraction analysis. The molecules of compound 1 exist in
the chair conformation with the axially oriented phenyl group. The computer simulation using DFT
approximation at the PBE/3ξ level has revealed the route of interconversion of the ring and the optimal
conformation of the phenyl group corresponding to the data of X-ray diffraction analysis.
Keywords: 1,3-dioxane, 5,5-bis(halomethyl)-1,3-dioxanes, X-ray diffraction analysis, conformers, computer
simulation
DOI: 10.1134/S1070363219020051
Substituted 1,3-dioxanes are interesting due to
special structural features and are widely applied as
synthons in fine organic synthesis [2–4]. For example,
5,5-bis(halomethyl)-1,3-dioxanes can be easily con-
verted into the mono- and diiodo-derivatives; the
process proceeds stereoselectively, predominantly at
the equatorial chloromethyl substituent [5].
The hitherto unknown 5,5-bis(bromomethyl)-2-methyl-
2-phenyl-1,3-dioxane was synthesized via the con-
densation of 2,2-bis(bromomethyl)-1,3-propanediol
with acetophenone (Scheme 1).
The results of X-ray diffraction investigation of the
obtained ketal are summarized in Tables 1 and 2. The
structure of the molecule of 5,5-bis(bromomethyl)-2-
methyl-2-phenyl-1,3-dioxane corresponded to the
chair conformation with the axial phenyl group (Cа,
see figure). The planes of the aromatic ring and the
О1–O5–С3–C14 fragment were practically orthogonal.
For the heteroatomic part of the heterocyclic ring, the
The conformational behavior of formals of 5,5-bis-
(halomethyl)-1,3-dioxanes at room temperature is
characterized by fast interconversion of the ring (at the
NMR timescale) [6]. On the contrary, the molecules of
2-substituted analogs exist predominantly in the chair
conformation with equatorial orientation of the
substituent at the С2 atom (Cе) [7, 8]. However,
conformational behavior of the ketals of the same
series has been scarcely studied. To fill in the gap, this
study was devoted to investigation of the structure and
conformational transformations of 5,5-bis(bromo-
Scheme 1.
C6H5
H3C
BrH2C
BrH2C
OH
+
C=O
OH
1
methyl)-2-methyl-2-phenyl-1,3-dioxane using H and
13С NMR spectroscopy, X-ray diffraction analysis, and
DFT simulation using the PBE/3ζ method imple-
mented in PRIRODA software package [9].
BrH2C
BrH2C
O C6H5
O CH3
H+
−H2O
199

200
KHAZHIEV et al.
Table 1. Crystallographic data and details of X-ray diffraction experiment
Parameter
Value
C13Н16О2Br2
364.06
Parameter
Value
4
Formula
М
Z
ρ
calc, mg/mm3
1.693
5.665
720.0
Т, K
293(2)
μ, mm–1
F(000)
Indexes range
Crystallographic system
Space group
Monoclinic
P21/с
–9 ≤ h ≤ 7
–26 ≤ k ≤ 20
–14 ≤ l ≤ 13
a, Å
6.9219(4)
Number of reflections used for refinement/number of
refined parameters
2777/145
b, Å
c, Å
19.0319(11)
11.2114(8)
GOOF
1.090
Final values of divergence factors for reflections with
R1 = 0.0861
I ≥ 2σ(I)
wR2 = 0.1492
β, deg
V, Å3
104.780(6)
Final values of divergence factors for all reflections
R1 = 0.1634
wR2 = 0.1815
1428.09(16)
Residual electronic density, e/Å‒3
0.47/–1.01
values of the C–O bond lengths (1.416–1.430 Å) and
bond angles (110°–113°) corresponded to conventional
values. The interplane angles between the 1,3-dioxane
ring fragments СОО and СООС (α1) as well as СООС
and ССС (α2) equaled 129.2(5)° and 130.7(5)°,
respectively. It should be noted that the heteroatomic
fragment of the molecule of the studied ketal was more
folded as compared to 5,5-bis(bromomethyl)-2-phenyl-
1,3-dioxane, the α1 value for the latter being 120.1°
[3]. The bromomethyl substituents, in accordance with
the earlier performed quantum-chemical simulations
[7], were in the gauche-position with respect to each
other (see figure), in the conformation corresponding
to the minimum of energy.
1Н and 13С NMR spectra demonstrate the
conformational homogeneity of the molecules of 5,5-
bis(bromomethyl)-2-phenyl-1,3-dioxane in solution.
1
The assignment of the signals in the Н and 13С NMR
spectra was performed using the data of 1D and 2D
spectroscopy (DEPT135, NOESY, COSYHH, and
HSQC techniques). The methylene protons at the
magnetically equivalent carbon atoms С4 and С6 of the
heterocyclic ring were diastereotopic (Δδ 0.26 ppm)
Table 2. Selected bond lengths and bond angles in the molecule of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane
d, Å
φ, deg
experiment
Bond
Bond angle
calculation
experiment
calculation
О1–С8
О1–С14
О5–С8
О5–С3
С8–С4
С6–С2
С6–С13
С2–Br1
С8–С2АА
1.434
1.432
1.435
1.431
1.538
1.525
1.529
1.989
1.525
1.416(8)
1.423(7)
1.430(7)
1.426(7)
1.530(8)
1.521(8)
1.532(8)
1.955(6)
1.507(8)
C14O1C8
С3О5С8
О1С8О5
О1С14С6
О5С3С6
С3С6С14
С6С2Br1
С6С13Br2
С2С6С13
113.6
113.8
110.5
111.3
112.1
105.4
114.1
114.1
113.1
113.8(4)
114.0(5)
110.1(5)
110.2(5)
110.6(4)
110.0(5)
113.6(4)
113.9(5)
113.0(5)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

STRUCTURE AND CONFORMATIONAL ANALYSIS
201
2
1
and appeared as doublets with J = 10.7 Hz in the Н
NMR spectrum. The methylene protons of the bromo-
methylene substituents at the С5 atom of the ring were
magnetically nonequivalent (Δδ = 0.90 ppm); the
NOESY experiment showed that the protons of the
axial СН2Br group resonated in a lower field.
The obtained results were confirmed by the data of
conformational analysis of 5,5-bis(bromomethyl)-2-
phenyl-1,3-dioxane at the PBE/3ζ level. The potential
energy surface (PES) contained three minimums
(conformers Cе, Cа, and 2,5-Т) and two transition
states TS-1 and TS-2 (Scheme 2). The simulations
were performed for the gauche-orientation of
bromomethyl substituents at the С5 atom of the
heterocyclic ring.
Structure of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-
dioxane molecule in the crystal.
The global minimum of the PES corresponded to
the Cа form (Table 3). The simulated values of the
bond lengths as well as bond and torsional angles were
close to the data of the X-ray diffraction experiment
(Table 2). The phenyl group, as in the case of the
molecule in the crystal (see figure), was orthogonal to
the О1–O5–С3–C14 plane of the heterocyclic ring (see
the atoms enumeration in the figure). Simulation of its
internal rotation in the course of scanning over the
С2АА–С8–С4–С12 torsion angle (φ) resulted in
appearance of a transition state in which the phenyl
group was oriented along the bisector plane of the
heterocyclic ring; the potential barrier for such rotation
(ΔG≠298) was 11.1 kcal/mol.
least stable. The transition states, half-chair conforma-
tions, differed in energy by 1.2 kcal/mol (ΔG≠298); the
maximum height of the potential barrier (9.2 kcal/mol)
was well consistent with the experimental data for
2-methyl-2-phenyl-1,3-dioxane [1]. Note also the
absence of an intermediate 1,4-twist minimum on the
PES, which is typical for the equilibriums of the
molecules of unsubstituted as well as the 2-, 4-, 5-,
2,5-, and 4,4-substituted 1,3-dioxanes [4].
In summary, the data of the X-ray diffraction
analysis, NMR spectroscopy, and computer simulation
solidly proved the conformational homogeneity of the
molecules of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-
1,3-dioxane existing in the chair conformation with
the axial phenyl group.
The 2,5-Т conformer showed the nearest local
minimum to the Cа form, whereas the Cе form was the
Scheme 2.
Minimums
C6H5
CH3
BrH2C
BrH2C
TS-1
C6H5
CH3
TS-2
BrH2C
BrH2C
O
O
O
O
O
BrH2C
O
C6H5
CH3
CH2Br
Cе
Ca
2,5-T
Transition state
C6H5
BrH2C
BrH2C
BrH2C
CH3
O
O
O
O
CH3
C6H5
BrH2C
TS-1
TS-2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

202
KHAZHIEV et al.
Table 3. Energy parameters of conformational transformations of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane
molecule according to the data of PBE/3ζ simulations
ΔЕ°, kcal/mol
ΔH° , kcal/mol
ΔG° , kcal/mol ΔS° , cal mol–1 K–1
а
0
298
298
(ΔG≠298
298
Conformers
–Е0 , Hartree
(ΔЕ≠0)
0
(ΔH≠298
)
)
(ΔS≠298
0
)
Cа
5802.274495
5802.269567
5802.270376
5802.261527
5802.258974
5802.262507
0
0
Cе
3.1
3.2
2.6
1.9
2,5-Т
TS-1
TS-2
2.6
2.6
2.1
1.7
(8.1)
(9.7)
(10.1)
(7.9)
(9.5)
(9.5)
(8.0)
(9.2)
(11.1)
(–0.4)
(1.2)
Rotation 2-Ph (Cа)
(–5.5)
а With ZPE.
EXPERIMENTAL
search procedure using PRIRODA software package.
The correspondence of the PES stationary points to the
transition states was confirmed by the presence of a
single imaginary frequency in the corresponding
Hessian, whereas no imaginary frequencies were found
for the points corresponding to the minimum.
NMR spectra were registered using a Bruker
Avance 400 spectrometer operating at 400.13 (1H) and
100.62 (13С) MHz, in CDCl3 with residual protons of
the solvent used as internal reference. X-ray diffraction
analysis was performed using an XCalibur Eos
automated four-circle diffractometer (graphite
monochromator, MoKα radiation, λ = 0.71073 Å,
ω-scanning, 2θmax = 62°). Collection and processing of
the data were performed using CrysAlisPro 1.171.36.20
software (Oxford Diffraction Ltd.). The structures
were solved via the direct method and refined by full-
matrix least square method under anisotropic
approximation for non-hydrogen atoms. Hydrogen
atoms were localized from the differential Fourier
synthesis and refined under isotropic approximation.
The calculations were performed using SHELX97
software [10]. The structural data were deposited at the
Cambridge Crystallographic Database Center (CCDC
1849061).
5,5-Bis(bromomethyl)-2-methyl-2-phenyl-1,3-di-
oxane was prepared via a method adopted from Ref.
[12], by refluxing an equimolar mixture (0.01 mol
each) of 2,2-bis(bromomethyl)-1,3-propanediol with
acetophenone in the presence of 0.1 g of p-toluene-
sulfonic acid. Yield 73%, mp 96–97°С (hexane–
1
ethanol 1 : 1). Н NMR spectrum, δ, ppm: 1.58 s (3Н,
CH3), 3.12 s (2Н, СН2Breq), 3.63 d (2Н, НА, J =
10.7 Hz), 3.89 d (2Н, НВ, J = 10.7 Hz), 4.02 s (2Н,
СН2Braх), 7.29–7.44 m (5Н, С6Н5). 13C NMR
spectrum, δ, ppm: 31.5 (C2), 36.1 (C13), 37.5 (C6), 66.1
(C3,14), 101.4 (C8), 126.5 (Сp), 128.2 (Сm), 129.0 (Со),
139.4 (Сipso). Found, %: С 42.79; Н 4.33; Br 44.01.
С13Н16Br2O2. Calculated, %: С 42.85; Н 4.39; Br
43.95.
Preliminary geometry optimization of the Cа
conformer of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-
1,3-dioxane was performed using АМ1 method
implemented in HyperChem 8.0 software [11]. The
obtained structure was investigated using PBE/3ζ
method (PRIRODA [9]). Simulation of conformational
transformations of the phenyl group in the Cа
conformer was performed by geometry optimization
with varying the С2АА–С8–С4–С12 torsion angle from
0° to 180°; simulation of interconversion of the ring
was performed by scanning over the transannular
СССО torsion angle from –60° to 60°. The values of
potential barriers were found by the transition states
FUNDING
Structural studies were performed at the Center for
Collective Usage “Agidel,” Institute of Petrochemistry
and Catalysis, Russian Academy of Sciences. This
study was financially supported by the Ministry of
Education and Science of Russian Federation in the
scope of project no. 16.1969.2017/4.6.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

STRUCTURE AND CONFORMATIONAL ANALYSIS
203
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