Sm-Catalyzed Synthesis and Biological Activity of Acyclic and Cyclic Azadiperoxides

Article abstract of DOI:10.1134/S1070428019050075

Acyclic diaminodiperoxides and cyclic azadiperoxides are synthesized by the reaction of 1,1-bis-(hydroperoxy)cycloalkanes with formaldehyde and primary arylamines in the presence of Sm-containing catalysts [SmCl₃·6H₂O, Sm(NO₃

Full text of DOI:10.1134/S1070428019050075

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 5, pp. 620–632. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 5, pp. 714–728.
Sm-Catalyzed Synthesis and Biological Activity of Acyclic
and Cyclic Azadiperoxides
N. N. Makhmudiyarovaa,*, R. Sh. Rakhimova, T. V. Tyumkinaa, E. S. Meshcheryakovaa,
A. G. Ibragimova, and U. M. Dzhemileva
a Institute of Petrochemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, Republic of Bashkortostan, 450075 Russia
*e-mail: natali-mnn@mail.ru
Received April 26, 2018; revised February 10, 2019; accepted February 14, 2019
Abstract—Acyclic diaminodiperoxides and cyclic azadiperoxides are synthesized by the reaction of 1,1-bis-
(hydroperoxy)cycloalkanes with formaldehyde and primary arylamines in the presence of Sm-containing
catalysts [SmCl3·6H2O, Sm(NO3)3·6H2O, SmCl3/γ-Al2O3, and Sm(NO3)3/γ-Al2O3]. The chemoselectivity of
this three-component reaction depends on the position of the substituent (F,Cl) in the phenyl ring of the primary
arylamines. Signals of the cyclic aminoperoxides were assigned considering the conformation dynamics of the
tetraoxazocane cycle with two rigid peroxide bonds. The structure of the acyclic diaminodiperoxides was
reliably determined by X-ray diffraction analysis. The synthesized acyclic diaminodiperoxides were found to
exhibit anticancer activity.
Keywords: acyclic diaminodiperoxides, cyclic azadiperoxides, arylamines, catalysis, heterocyclization,
chemoselectivity, conformational analysis, X-ray diffraction analysis, anticancer activity.
DOI: 10.1134/S1070428019050075
The ability of peroxides to exhibit antimalarial,
anticancer, and anthelmintic activity of the compounds
of depends on the molecular structure, as well as on
whether they contain heteroatomic substituents [1–13].
Nitrogen-containing asymmetric peroxides are most
promising for the treatment of malaria.
amounts of Sm(NO3)3·6H2O (5 mol %). The reaction
direction depends on the position of the substituent (F,
Cl) in the benzene ring of arylamines 1a–1f. The
reaction of о-chloro(fluoro)anilines 1a, 1d with form-
aldehyde and 1,1-bis(hydroperoxycycloalkanes 2‒4 gave
N,N'-[cycloalkane-1,1-diyl (diperoxymethanediyl)]di-
anilines 5a, 5d‒7a, 7d in yields of 63–75%. The
analogous reaction with p-chloro(fluoro)anilines 1c, 1f
instead of arylamines 1a, 1d formed cyclic tetra-
oxazaspiroalkanes 8c, 8f‒10c, 1f in yields of 75‒87%.
The three-component condensation with m-chloro-
(fluoro)anilines 1b, 1e produce 1 : 1 mixtures of acyclic
11b, 11e‒13b, 13e and cyclic aminoperoxides 14b,
14e‒16b, 16e (Scheme 1).
Azaperoxides are difficult or sometimes impossible
to synthesize, which is associated with the low
resistance of the peroxyl group to the action of amines
[14]. Earlier [15, 16] we developed selective synthesis
of aminodiperoxides by the recyclization of penta-
oxacanes [17] in the presence of primary amines.
Proceeding with this research, as well as with the aim
to develop an efficient synthetic approach to acyclic
and cyclic aminodiperoxides, we have studied the three-
component heterocyclization of 1,1-bis(hydroperoxy)-
cycloalkanes with formaldehyde and primary
arylamines, catalyzed by Sm salts [SmCl3·6H2O,
Sm (NO3)3·6H2O, SmCl3/γ-Al2O3, Sm (NO3)3/γ-Al2O3].
Presumably, ortho substituents (F, Cl) in the
benzene ring create steric hindrance to the
condensation of anilines 1a‒1f with two formaldehyde
molecules, and the reaction involves the intermediate
formation of aminoalcohols, which further react with
1,1-bis(hydroperoxy)cycloalkane to form acyclic
products 5‒7. If the substituent occupies the para-
position, no steric hindrance takes place, and the
reaction involves the intermediate formation of 2-aryl-
Amidodiperoxides formed within 2‒3 min upon the
addition of a solution of an aromatic amine in THF at
15‒20°С to a mixture of 1,1-bis(hydroperoxy)cyclo-
alkane and formaldehyde in the presence of catalytic
620

621
Scheme 1.
NH2
R
R
HO
H
N
H
O
O
O
O
N
1a, 1d
R
( )n
N
H
NH2
R
5a, 5d_7a, 7d
OH
OH
O
O
R
1c, 1f
2CH2O
+
[Sm]
R
N
N
R
( )n
O
OOH
OOH
O
8c, 8f_10c, 10f
( )n
NH2
2_4
HO
OH
HO
H
R
N
N
1b, 1e
+
R
R
R
O
O
H
N
O
O
O
O
O
O
N
+
( )n
( )n
N
H
R
R
14b, 14e_16b, 16e
11b, 11e_13b, 13e
R = Cl (a‒с), F (d‒f); n = 1 (2, 5, 8, 11, 14), 2 (3, 6, 9, 12,15), 3 (4, 7, 10, 13, 16); [Sm] = Sm(NO3)3·6H2O.
2-azapropane-1,3-diols, whose subsequent reaction with
1,1-bis(hydroperoxy)cycloalkane leads to cyclic
peroxides. With meta-substituted aniline, both reaction
pathways are realized; as a result, both cyclic and acyclic
aminoperoxides are formed (Scheme 1).
aldehyde, catalyzed by 1,1-bis(hydroperoxy)cyclo-
alkanes 2‒4, occurs [18] to form symmetrical 1,3,5-
triaryl-1,3,5-triazinanes 17a, 17d, 18c, 18f, 19b, and
19c. The reactions of o-chloro(fluoro)anilines 1a and
1d with formaldehyde and 1,1-bis(hydroperoxy)cyclo-
alkanes 2‒4 give rise to acyclic N,N'-[cycloalkane-1,1-
diyl(bisperoxymethanediyl)]dianilines 5a, 5d‒7a, and
7d an 1,3,5-tris(2-halophenyl)-1,3,5-triazinanes 17a
and 17d in a 1 : 2 ratio (Scheme 2, Table 1). The three-
In the absence of catalyst, along with the two
mentioned pathways, the competitive weakly basic
condensation of aniline derivatives 1a‒1f with form-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

622
Scheme 2.
R
N
R
1c, 1f
1a, 1d
8c, 8f_10c, 10f
2_4
2CH2O
N
+
5_7a, 7d
+
+
R
N
N
N
R
N
1b, 1e
R
R
R
18c, 18f
17a, 17d
11b, 11e_13b, 13e
14b, 14e_16b, 16e
N
+
+
R
N
N
R
19b, 19e
R = Cl (a‒с), F (d‒f).
component condensation with p-haloanilines 1c and 1f
forms cyclic tetraoxazaspiroalkanes 8c, 8f‒10c, 10f and
triazines 18c, 18f. The three-component condensation
with m-chloro(fluoro)anilines 1b and 1e gives rise to a
mixture of acyclic 1,1-bis[N-(peroxymethyl)-N-aryl-
amino]cycloalkanes 11b, 11e‒13b, and 13e, cyclic
tetra-oxazaspiroalkanes 14b, 14e‒16b, 16e and 1,3,5-
tris[3-chloro(fluoro)phenyl]-1,3,5-triazinanes 19b, 19e
(the ratios of the products are listed in the table).
The structure of aminoperoxides 13b, 12b, 12e, and
9f was established by single-crystal X-ray diffraction
(XRD) analysis (Fig. 1, Table 2). The XRD data were
collected at room temperature (293 K).
Table 1. Yields, %, of triazinanes 17a, 17d, 18c, 18f, 19b, 19e and acyclic 5a, 5d‒7a, 7d, 11b, 11e‒13b, 13e and cyclic amino-
peroxides 8c, 8f‒10c, 10f, 14b, 14e‒16b, 16e
Run no.
R
Triazinane
Acyclic diaminodiperoxide
Cyclic azadiperoxide
o-F
m-F
p-F
o-Cl
m-Cl
p-Cl
50 (17d)
45 (19e)
60 (18f)
52 (17a)
55 (19b)
64 (18c)
30 (5d)
23 (11e)
–
25 (5a)
20 (11b)
–
–
20 (14e)
29 (8f)
–
18 (14b)
31 (8c)
1
o-F
m-F
p-F
o-Cl
m-Cl
p-Cl
o-F
m-F
p-F
49(17d)
46 (19e)
48 (18f)
62 (17a)
50 (19b)
53 (18c)
64(17d)
60 (19e)
58 (18f)
56 (17a)
59 (19b)
48 (18c)
24 (6d)
19 (15e)
–
25 (6a)
25 (15b)
–
26 (7d)
27 (13e)
–
22 (7a)
20 (13b)
–
–
15 (15e)
20 (9f)
–
25 (15b)
20 (9c)
–
22 (16e)
23 (10f)
–
26 (16b)
18 (10c)
2
3
o-Cl
m-Cl
p-Cl
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

623
13b
12b
12е
9f
Fig. 1. Structures of aminoperoxides 13b, 12b, 12e, and 9f by XRD data. The nonhydrogen atoms are presented by thermal
ellipsoids drawn at a 30% probability level.
Compounds 13b, 12b, and 9f form orthorhombic
crystals, whereas the monoclinic crystal system is
characteristic of compound 12e. Molecule 13b (Fig. 1)
in the crystal takes a special position and is located on
the symmetry axis С2, which passes through the С2
atom and bisector of the HAС11HB angle. Molecules
12e, 12b, and 9f in the respective crystals are in
general positions. Aminoperoxide 13b has its own
second-order symmetry axis С2, whereas the other
aminoperoxides have no symmetry elements, i.e. they
only have the first-order axis С1. The cyclohexane
fragment in molecules 12b, 12e, and 9f takes a chair
conformation, and the seven-membered carbocycle in
compound 13b has a twist conformation. The bond
lengths and angles are contained in the ciffiles.
Aminoperoxide 9f has a tetraoxazocane fragment
which takes a twist–boat–chair conformation, and the
p-fluoroaryl substituent is axial with respect to this
fragment.
1
The cyclic aminoperoxides were studied by H and
13C NMR spectroscopy to find that at room
temperature they exist as equilibrium mixtures of
conformers with different spatial organization of the
1
ring. The H and 13C NMR spectra of the synthesized
cyclic azaperoxides show double sets of proton and
carbon signals both in DMSO and in CDCl3 and Tol-d6.
1
In the H NMR spectra in apolar solvents of, for
example, compound 9с, the NCH2 methylene proton
signals appear as doubled doublets at 5.18 and
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624
Table 2. Crystallographic data and refinement parameters of structures 9f, 12b, 12e, and 13b
Parameter
9f
293
12b
293
12e
293
13b
293
Т, K
Brutto formula
M, Da
C14H18FNO4
283.29
Rhombic
Pbca (№ 61)
12.4485(6)
10.2927(6)
21.8055(10)
90
C20H24Cl2N2O4
427.31
C20H24F2N2O4
394.41
C21H26Cl2N2O4
441.34
Rhombic
P21212 (№ 18)
5.6933(12)
15.024(3)
12.615(3)
90
Syngony
Space group
a, Å
Rhombic
P212121 (№ 19)
5.8964(4)
15.0223(9)
23.2043(18)
90
Monoclinic
P21/n (№ 14)
12.3217(8)
5.7679(6)
27.155(2)
90
b, Å
c, Å
α, deg
β, deg
90
90
92.820(12)
90
90
γ, deg
90
90
90
Volume, Å3
2793.9(2)
8
2055.4(2)
4
1927.6(3)
4
1079.1(4)
2
Z
d
calc, g/cm3
1.347
1.381
1.359
1.358
μ, mm–1
0.107
0.344
0.107
0.330
2θmax, deg
58.06
58.56
62.10
58.40
Measured reflections
14961
13324
4979
6240
Unique reflections (Rint)
3246(Rint 0.0522)
4882 (Rint 0.0222)
3513 (Rint 0.0131)
2342 (Rint 0.0366)
R1 [I ≥ 2σ(I)]
wR2
0.0939
0.2702
0.0527
0.1531
0.0903
0.3009
0.09631
0.2441
CCDC
1585916
1575320
1575321
1575319
5.00 ppm (2J 14.3 Hz) and 4.94 and 4.89 ppm (2J
12.0 Hz), with the intensity ratio ~1 : 2.7 (Fig. 2).
computations in the gas phase (Gausian 09). It was
found that the eight-membered N,O-heteroring can
take the conformations chair–chair А, twist–chair В,
and boat–chair C; therewith, the B' conformer, which
is slightly higher in energy on the PES and has
different dihedral angles of the oxazocine ring, is also
optimized for the twist form (Fig. 3). The most favored
are the energetically close conformers А and B, the
latter of which crystallizes.
The HSQC experiment showed that the more
intense upfield doublets are connected with the upfield
carbon signal at 85.1 ppm. When the temperature is
decreased to 243 K, this proton signal coalesces,
whereas at 218 K it splits into two signals, and the
spectrum shows signals of three conformers (Fig. 2).
Simultaneously, the pair of signals at 4.93 and 5.15 ppm,
which are presumably averaged signals of different
heteroring conformers, too, transform into two doubled
doublets (Fig. 2).
When assigning the signals of the conformers, we
noticed a strongly pronounced deshielding effect of the
proton signals of one of the methylene groups of the
spirocyclohexane fragment, located α to the quaternary
carbon atom, for the minor conformer, whose signals
are observed in the weak-field region and does not
For structural assessment of the conformers we
determined minima on the potential energy surface
(PES) of compound 9c by B3LYP/6-31G(d,2p)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

625
1H
13C
298 K
263 K
243 K
B
A
C
C
A
B
218 K
88.0 87.0 86.0 85.0
ppm
5.2
5.0
4.8
4.6
ppm
Fig. 2. Fragment 1H and 13С NMR spectra of compound 9с in toluene (NCH2O signals region).
change in the 223–298 K range. This observation
allowed us to suggest that, among the theoretically
found stable conformers, such situation can be realized
in the chair–chair conformer А, where the aryl and
cycloxane fragments are proximate to each other (dcalc
2.8 Å). Evidence for this suggestion was obtained from
NOE experiments (Fig. 4) and calculated chemical
shifts of the characteristic carbon atoms (Table 3).
А (0.0 kcal/mol)
B (0.3 kcal/mol)
B' (1.4 kcal/mol)
С (3.2 kcal/mol)
Fig. 3. Stable ring conformers in compound 9c.
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626
δC 32.6 ppm
The APCI mass spectrum of acyclic diperoxide 7a
displays peaks of the [С7H7ClN]+• and [С7H7ClNO]+•
radical cations formed by C–O or O–O bond cleavage.
δH 1.5 ppm
Under APCI conditions, the studied cyclic
diperoxides mainly form positive ions due to con-
current cleavage of the C–O and O–O, C–O and C–N,
and C–O and C–O bonds in the protonated molecule.
δC 29.6 ppm
δH 2.1 ppm
The APCI mass spectra of compounds 9c, 9f, 10f,
14b, 15b, 15e, 16b, and 16e display peaks of three
characteristic fragment ions [С7H6HlgN + H]+,
[С7H6HlgNO + H]+, and [С8H8HlgNO3 + H]+, which are
common for all these compounds, as well as peaks of
the associates of these ions with one or two solvent
(acetonitrile) molecules.
Fig. 4. Assignment of the NMR signals of conformer А by
NOESY data.
The 1H and 13C NMR signals of the other
conformers are impossible to assign with a high degree
of reliability because of the closeness of their; moreover,
the signals of the cyclohexane fragment strongly
undergo strong broadening with decreasing tempe-
rature. Apparently, the carbon signal at 84.3 ppm,
which is connected to the methylene proton signals
with quite different chemical shifts (∆δ 0.6 ppm) and
In additions, the mass spectra of compounds 9f,
10f, 14b, 15e, 16b, and 16e show peaks characteristic
of these compounds. The [С8H8FNO + H]+ ion peak
(m/z 154) are observed in the mass spectra of
compounds 10f and 16e, which is likely to be
explained by the presence of a 7-membered ring and a
fluorine atom in their structures. The mass spectrum of
compound 16b shown another peak, which is
characteristic of this compound: [С8H8ClN + H]+, m/z
154. The mass spectra of compounds 9f, 14b, and 15e
show molecular ion [M + H]+ peaks at m/z 284, 286,
and 284, respectively, which we associate with the
presence of a six-membered (9f and 15e) or a 5-
member ring (14b), taking into account the absence of
molecular ions in the spectra of 10f and 16e containing
a 7-membered ring. The fluorine substituent, too,
stabilizes the molecular ion, as judged from the fact
that chloro derivatives 9c and 15b do not give
molecular ions.
2
the geminal constant JВ of 9.8 Hz in the HSQC
spectrum (Fig. 2), belongs to conformer В (or В + В').
Because the diastereotopicity of the corresponding
protons in conformers А and С, whose structure is a
combination of the classical chair and boat
conformations, is less pronounced, the 2J constants are
also close (~14.4 Hz). Using dynamic low-temperature
NMR spectroscopy, we estimated the barriers to
inversion of the heteroring [∆G≠ 12.2 kcal/mol
(±0.1 kcal/mol)] between structures В (and/or B') and С.
Extrapolating the resulting data to compounds 8с,
8f, 9f, 10с, and 10f, as well as 14b, 14e–16b, and 16e,
which show the same NMR spectral characteristic, we
established at room temperature the eight-membered
aminoperoxides preferentially exist as chair–chair
conformers А, whereas the boat–chair С and twist–
boat conformers В are present in equilibrium. It should
be noted that the conformationally rigid peroxide
fragments, too, give a series of singlets in the 1H NMR
spectra of linear diperoxides.
Biological activity assay. The newly synthesized
cyclic and acyclic aminoperoxides 10f, 13b, 12b, and
12e were tested for anticancer activity in vitro on
60 cell lines of different human cancers (lungs, colon,
central nervous system, ovary, kidney, prostate, breast,
leukemia, and melanoma) by the protocols available at
the US National Cancer Institute [19–24] (concen-
tration 10–5 M). Each cell line was inoculated and pre-
incubated in a microtiter plate, after which the test
compound was added, and the culture was incubated
for 48 h. The results are presented as percent growth of
the treated cells compared to untreated control cells.
According to the NCI criteria (growth inhibition of any
cancer cell line to ~ 32% or less), compound 10f was
inactive, whereas compounds 13b, 12b, and 12e, that
Table 3. Calculated and experimental 13С NMR chemical
shifts of conformers А, B, and C of compound 9f
Conformer
СH2calc
СH2exp
Ccalc
Cexp
А
В
С
97.1
92.5
93.5
87.6
84.3
85.1
124.6
120.6
122.3
111.4
108.8
108.8
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

627
inhibit cell growth or causes death of certain cell lines,
were have been identified as active.
atoms. The hydrogen atoms were located by difference
Fourier synthesis and refined with isotropic
displacement parameters. Calculations were performed
using SHELX [26].
Acyclic diaminodiperoxide 13b is active against SR
leukimia (5.27%), LOX IMVI melanoma (‒85.23%),
IGROV1 ovarian cancer (7.21%), and UO-31 kidney
cancer cells (‒47.31%). Compound 12b is active
against K-562 (‒40.99%) and SR leukemia (‒41.42%),
A549/ATCC breast cancer (3.10%), HOP-92 (‒46.34%),
NCI-H522 (14.69%), LOX IMVI melanoma cells
(‒86.08%), IGROV1 ovarian cancer (‒33.19%), and
786-0 (10.78%) and UO-31 kidney cancer cells
(‒73.73%). Aminoperoxide 12e inhibits growth of SR
leukemia (31.48%), LOX IMVI melanoma (‒68.86%),
and UO-31 kidney cancer cells (‒58.17%). It appears
that compounds 13b, 12b, and 12e may be promising
as potential anticancer agents for more detailed in vitro
studies.
Quantum-chemical calculations were performed
using Gaussian 09 [27]. Geometry optimization,
vibrational analysis, and calculation of the entropy and
thermodynamic corrections to total energy were
performed at the B3LYP6-31G(d,p) level of theory
[28–30]. Thermodynamic parameters were determined
at 298 K. The NMR shifts were calculated by the
GIAO method [31] incorporated in Gaussian 09. The
quantum-chemical data were processed using
ChemCraft [32].
Anticancer activity in vitro. The anticancer activity
assay developed at the US National Cancer Institute is
described in [19–24] and at www.dtp.nci.nih.gov.
EXPERIMENTAL
Heterocyclization of 1,1-bis(hydroperoxy)cyclo-
alkanes with formaldehyde and primary amines,
catalyzed by Sm(NO3)3·6H2O (general procedure).
Tetrahydrofuran (5 mL), 37% aqueous formaldehyde
(1.46 mL, 20 mmol), and corresponding 1,1-bis(hydro-
peroxy)alkane were loaded at ~20°С into a Schlenk
flask mounted on a magnetic stirrer, after which
Sm(NO3)3·6H2O [0.022 g, 5 mol % with respect to 1,1-
bis(hydroperoxy)cycloalkane)] and, after 15-min
stirring, 1 mmol of arylamine were added. The reaction
mixture was stirred for 6 h at ~20°С and then THF was
evaporated. Diethyl ether (10 mL) was dded to the
residue, and the mixture was washed with water (4 × 5 mL).
The ether layer was dried over MgSO4 and concent-
rated to isolate aminoperoxides stable at room tempe-
rature. Reaction progress was monitored by TLC,
eluent C6H12‒EtOAc, 5 : 1, developer iodine vapor.
The H and 13С NMR spectra were registered on a
1
Bruker Avance 400 spectrometer (400 and 100 МHz,
respectively) in CDCl3 and DMSO-d6, internal
reference TMS. The 2D homonuclear (COSY) and
heteronuclear experiments (HSQC, HMBC) were
accomplished by standard Bruker procedures at the
same operating frequencies. The APCI mass spectra
were obtained on a Shimadzu LCMS-2010EV system
in the positive ion mode at the ionization electrode
potential of 4.5 kV; APCI interface temperature 250°C,
heater temperature 200°C, desolvation line tempe-
rature 230°C; nebulizer gas (nitrogen) flow rate
1.5 L min–1; RF lens voltage (Q-massive) 5 V, flow
rate of mobile phase (acetonitrile‒water, 83 : 17)
0.1 mL min–1.
Elemental analysis of performed on a Сarlo Erba
1106 analyzer. Reaction progress was monitored by
TLC on Sorbfil (PTSKh-AF-C), eluent C6H12‒EtOAc,
10 : 1, developer iodine vapor. Column chromatog-
raphy was performed on KSK silica gel (100–200 µm).
N,N'-[Cyclopentane-1,1-diyl(bisperoxymethane-
diyl)]di(2-chloroaniline) (5a). Yield 0.31 g (75%),
yellow oil. H NMR spectrum (CDCl3), δ, ppm: 1.36‒
1
1.46 m (4H, H2С), 1.60‒1.72 m (4H, H2С), 5.24‒5.20
m (4H, OH2СN), 6.74‒6.77 m (2H, HС), 6.97‒6.99 m
(2H, HС), 7.14‒7.16 m (2H, HС), 7.28‒7.30 m (2H,
HС). 13С NMR spectrum (CDCl3), δ, ppm: 21.7, 30.1,
85.6, 109.4, 115.2, 117.4, 121.6, 130.1, 135.4, 147.7.
Found, %: C 55.10; H 5.34; Cl 16.97; N 6.76.
C19H22Cl2N2O4. Calculated, %: C 55.22; H 5.37; Cl
17.15; N 6.78.
X-ray diffraction analysis was performed on a
Rigaku/Oxford Diffraction Xcalibur/Gemini ЕOS
diffractometer with an EOS CCD area detector
(graphite monchromator, MoKα radiation, λ 0.71073 Å,
ω-scanning, 2θmax 62°). Data collection and processing
were performed using CrysAlisPro Oxford Diffraction
software [25]. The structure was solved by the direct
method and refined by full-matrix least squares with
anisotropic temperature factors for nonhydrogen
N,N'-[Cyclopentane-1,1-diyl(bisperoxymethane-
diyl)]di(2-fluoroaniline) (5d). Yield 0.26 g (70%),
1
light yellow oil. H NMR spectrum (CDCl3), δ, ppm:
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1.57‒1.75 m (4H, H2С), 1.84‒1.99 m (4H, H2С), 5.08 d
(4H, OH2СN, J 10 Hz), 5.19 d (4H,OH2СN, J 10 Hz),
6.70‒6.96 m (6H, HС), 7.02‒7.08 m (4H, HС). 13С
NMR spectrum (CDCl3), δ, ppm: 24.5, 33.1, 79.9,
110.1, 113.9, 115.1 d (J 15 Hz), 119.0 d (J 7 Hz),
124.5, 134.3, 151.6 d (J 190 Hz). Found, %: C 59.96;
H 5.81; F 9.90; N 7.33. C19H22F2N2O4. Calculated, %:
C 59.99; H 5.83; F 9.99; N 7.36.
6.99 m (2H, HС), 7.04‒7.13 m (4H, HС). 13С NMR
spectrum (CDCl3), δ, ppm: 22.7, 30.5, 33.5, 78.6,
109.0, 113.94, 114.74 d (J 15 Hz), 116,97, 118.46 d (J
6 Hz), 124.51, 134.10, 151.68 d (J 190 Hz). Found, %:
C 61.73; H 6.40; F 9.25; N 6.83. C21H26F2N2O4.
Calculated, %: C 61.75; H 6.42; F 9.30; N 6.86.
9-(4-Chlorophenyl)-6,7,11,12-tetraoxa-9-aza-
spiro[4.7]dodecane (8c). Yield 0.21 g (75%), light
yellow powder, mp 61‒62°С. 1H NMR spectrum
(CDCl3), δ, ppm: 2.11‒2.14 m (2H, H2C, conformer A),
1.56‒1.69 m (4H, H2С), 1.81‒1.91 m (4H, H2С), 5.35
and 5.74 d (4H, OH2СN, conformer A, J 12 Hz), 5.35‒
5.38 m (4H, OH2СN, conformers B + C), 6.52‒6.74 m
(2H, HС), 7.04‒7.12 m (2H, HС). 13С NMR spectrum
(CDCl3), δ, ppm: 24.6, 32.9, 86.0 (conformer A), 87.0
(conformers B + C), 115.0, 115.9, 116.8, 129.1, 144.7.
Mass spectrum (APCI), m/z (Irel, %): 284 (4) [M + H]+,
227 (84) [C8H8FNO3 + H + CH3CN]+, 186 (24)
[C8H8FNO3 + H]+, 181 (100) [C7H6FNO + H +
CH3CN]+, 165 (51) [C7H6FN + H + CH3CN]+, 140 (15)
[C7H6FNO+H]+, 124 (26) [C7H6FN + H]+. Found, %: C
54.63; H 5.62; Cl 12.37; N 4.87. C13H16ClNO4.
Calculated, %: C 54.65; H 5.64; Cl 12.41; N 4.90.
N,N'-[Cyclohexane-1,1-diyl(bisperoxymethane-
diyl)]di(2-chloroaniline) (6a). Yield 0.28 g (67%),
1
light yellow oil. H NMR spectrum (CDCl3), δ, ppm:
1.32‒1.40 m (6H, H2С), 1.68‒1.76 m (4H, H2С), 5.24‒
5.29 m (4H, OH2СN), 6.58‒6.62 m (2H, HС), 6.68‒
6.71 m (2H, HС), 7.04‒7.15 m (2H, HС), 7.26‒7.28 m
(2H, HС). 13С NMR spectrum (CDCl3), δ, ppm: 22.5,
25.3, 30.5, 78.4, 109.4, 113.4, 118.9, 119.0, 128.2,
129.5, 142.6. Found, %: C 56.20; H 5.63; Cl 16.50; N
6.54. C20H24Cl2N2O4. Calculated, %: C 56.22; H 5.66;
Cl 16.59; N 6.56.
N,N'-[Cyclohexane-1,1-diyl(bisperoxymethane-
diyl)]di(2-fluoroaniline) (6d). Yield 0.29 g (74%),
1
light yellow oil. H NMR spectrum (CDCl3), δ, ppm:
1.32‒1.46 m (6H, H2С), 1.67‒1.73 m (4H, H2С), 5.18‒
5.24 m (4H, H2С), 6.64‒6.68 m (2H, HС), 6.72‒6.79 m
(4H, HС), 6.94‒6.98 m (4H, HС), 7.02‒7.06 m (4H,
HС). 13С NMR spectrum (CDCl3), δ, ppm: 22.4, 25.3,
30.5, 78.4, 109.2, 115.1 d, (J 15 Hz), 118.1 d (J 6 Hz),
124.9, 136.3 d (J 88 Hz), 151.3 d (J 189 Hz). Found,
%: C 60.88; H 6.11; F 9.57; N 7.07. C20H24F2N2O4.
Calculated, %: C 60.90; H 6.13; F 9.63; N 7.10.
9-(4-Fluorophenyl)-6,7,11,12-tetraoxa-9-azaspiro
[4.7]dodecane (8f). Yield 0.21 g (79%), colorless
1
crystals, mp 47‒49°С. H NMR spectrum (CDCl3), δ,
ppm: 2.11‒2.14 m (2H, H2C, conformer A), 1.56‒1.69
m (4H, H2С), 1.81‒1.91 m (4H, H2С), 5.35 and 5.74 d
(4H, OH2СN, conformer A, J 12 Hz), 5.35‒5.38 m
(4H, OH2СN, conformers B+C), 6.52‒6.74 m (2H,
HС), 7.04‒7.12 m (2H, HС). 13С NMR spectrum
(CDCl3), δ, ppm: 24.3, 32.7, 86.4 (conformer A), 87.5
(conformers B + C), 115.7 d (J 18 Hz), 119.12 d (J
6 Hz), 119.7, 143. 9 d (J 8 Hz), 157.58 d (J 189 Hz).
Found, %: C 57.97; H 5.96; F 7.05; N 5.17.
C13H16FNO4. Calculated, %: C 57.99; H 5.99; F 7.06;
N 5.20.
N,N'-[Cycloheptane-1,1-diyl(bisperoxymethane-
diyl)]di(2-chloroaniline) (7a). Yield 0.3 g (72%),
1
light yellow oil. H NMR spectrum (CDCl3), δ, ppm:
1.41‒1.61 m (8H, H2С), 1.89‒1.95 m (4H, H2С), 5.19‒
5.22 m (4H, NСH2O), 6.71‒6.80 m (4H, HС), 7.08‒
7.11 m (2H, HС), 7.30‒7.33 m (4H, HС). 13С NMR
spectrum (CDCl3), δ, ppm: 22.7, 30.1, 33.2, 78.1,
113.5, 113.6, 114.2, 118.8, 119.0, 128.2, 129.6, 142.6.
Mass spectrum (APCI), m/z (Irel, %): 197 (36)
[C7H6ClNO + H + CH3CN]+, 181 (54) [C7H6ClN + H +
CH3CN]+, 156 (8) [C7H6ClNO + H]+, 140 (100)
[C7H6ClN + H]+. Found, %: C 57.12; H 5.91; Cl 15.97;
N 6.32. C21H26Cl2N2O4. Calculated, %: C 57.15; H
5.94; Cl 16.06; N 6.35.
10-(4-Chlorophenyl)-7,8,12,13-tetraoxa-10-aza-
spiro[5.7]tridecane (9c). Yield 0.23 g (79%), white
1
powder, mp 93‒94°С. H NMR spectrum (CDCl3), δ,
ppm: 1.41‒1.45 m (4H, H2С), 1.50‒1.61 m (4H, H2С),
1.65‒1.81 m (4H, H2С), 2.03 br.s (4H, H2С, conformer
A), 5.30 d and 5.62 d (4H, OH2СN, conformer A, J
12 Hz), 5.39 d (4H, OH2СN, conformers B + C, J
12 Hz), 7.01‒7.04 m (2H, HС), 7.25‒7.28 m (4H, HС).
13С NMR spectrum (CDCl3), δ, ppm: 22.6, 25.2, 30.1,
85.9, 109.3, 118.6, 129.1, 145.5 (conformer A), 22.7,
25.1, 29.5, 88.7, 113.0, 119.9, 129.3, 145.5 (confor-
mers B + C). Mass spectrum (APCI), m/z (Irel, %): 243
N,N'-[Cycloheptane-1,1-diyl(bisperoxymethane-
diyl)]di(2-fluoroaniline) (7d). Yield 0.27 g (68%),
1
1
light yellow oil. H NMR spectrum H (CDCl3), δ,
ppm: 1.43‒1.69 m (8H, H2С), 1.88‒1.99 m (4H, H2С),
5.20‒5.22 m (4H, H2С), 6.70‒6.79 m (2H, HС), 6.96‒
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(100) [C8H8ClNO3 + H + CH3CN]+, 238 (13)
[C7H6ClNO + H + 2CH3CN]+, 202 (9) [C8H8ClNO3 +
H]+, 197 (47) [C7H6ClNO + H + CH3CN]+, 181 (27)
[C7H6ClN + H + CH3CN]+, 156 (11) [C7H6ClNO + H]+,
140 (28) [C7H6ClN + H]+. Found, %: C 56.07; H 6.03;
Cl 11.80; N 4.63. C14H18ClNO4. Calculated, %: C
56.10; H 6.05; Cl 11.83; N 4.67.
%): 227 (71) [C8H8FNO3 + H + CH3CN]+, 222 (19)
[C7H6FNO + H + 2CH3CN]+, 186 (18) [C8H8FNO3 +
H]+, 181 (100) [C7H6FNO + H + CH3CN]+, 165 (67)
[C7H6FN + H + CH3CN]+, 154 (15) [C8H8FNO + H]+,
140 (10) [C7H6FNO + H]+, 124 (39) [C7H6FN + H]+.
Found, %: C 60.57; H 6.76; F 6.36; N 4.69.
C15H20FNO4. Calculated, %: C 60.60; H 6.78; F 6.39;
N 4.71.
10-(4-Fluorophenyl)-7,8,12,13-tetraoxa-10-
azaspiro[5.7]tridecane (9f). Yield 0.23 g (82%), light
brown crystals, mp 50‒50°С. 1H NMR spectrum
(DMSO-d6), δ, ppm: 1.35‒1.41 m (2H, H2С), 1.43‒
1.46 m (4H, H2С), 1.65‒1.66 m (4H, H2С), 1.90 br.s
(4H, H2С, conformer A), 5.36 d and 5.76 d (4H,
OH2СN, conformer A, J 12 Hz,), 5.36‒5.37 m (4H,
OH2СN, conformers B + C), 7.07‒7.14 m (4H, HС).
13С NMR spectrum (DMSO-d6), δ, ppm: 22.7, 25.1,
30.1, 86.1, 108.7, 115.8 d (J 17 Hz), 118.7 d (J 7 Hz),
143.6, 157.46 d (J 188 Hz, conformer A), 22.8, 24.9,
29.5, 88.6, 111.0, 116.2 d (J 18 Hz), 119.8 d (J 7 Hz),
143.6, 157.5 d (J 188 Hz, conformers B + C). Found,
%: C 59.33; H 6.35; F 6.67; N 4.91. C14H18FNO4.
Calculated, %: C 59.36; H 6.40; F 6.71; N 4.94.
N,N'-[Cyclopentane-1,1-diyl(bisperoxymethane-
diyl)]di(3-chloroaniline) (11b). Yield 0.18 g (44%),
light yellow oil. H NMR spectrum (DMSO-d6), δ,
1
ppm: 1.45‒1.48 m (4H, H2С), 1.56‒1.63 m (4H, H2С),
5.11‒5.12 m (4H, NСH2O), 6.95‒6.99 m (2H, СH, J
10 Hz), 7.05‒7.07 m (2H, HС), 7.26‒7.29 m (4H, HС).
13С NMR spectrum (DMSO-d6), δ, ppm: 24.3, 32.9,
75.6, 115.4, 116.6, 119.9, 120.8, 130.9, 134.0, 148.4.
Found, %: C 55.20; H 5.34; Cl 17.12; N 6.75.
C19H22Cl2N2O4. Calculated, %: C 55.22; H 5.37; Cl
17.15; N 6.78.
N,N'-[Cyclopentane-1,1-diyl(bisperoxymethane-
diyl)]di(3-fluoroaniline) (11e). Yield 0.19 g (50%),
1
light yellow oil. H NMR spectrum (DMSO-d6), δ,
ppm: 1.45‒1.48 m (4H, H2С), 1.56‒1.64 m (4H, H2С),
5.13‒5.14 m (4H, NСH2O), 6.71‒74 m (2H, HС),
6.91‒6.94 m (4H, HС), 7.26‒7.30 m (2H, HС). 13С
NMR spectrum (DMSO-d6), δ, ppm: 24.3, 33.9, 78.5,
103.1 d (J 25 Hz), 107.2 d (J 21 Hz), 112.7, 119.2,
130.1 d (J 17 Hz), 148.1, 162.7 d (J 191 Hz). Found,
%: C 59.96; H 5.80; F 9.97; N 7.34. C19H22F2N2O4.
Calculated, %: C 59.99; H 5.83; F 9.99; N 7.36.
11-(4-Chlorophenyl)-8,9,13,14-tetraoxa-11-
azaspiro[6.7]tetradecane (10c). Yield 0.27 g (87%),
1
light yellow oil. H NMR spectrum (DMSO-d6), δ,
ppm: 1.40‒1.59 m (8H, H2С), 1.85‒1.93 m (4H, H2С),
2.06 br.s (4H, H2С, conformer A), 5.24 and 5.36 d
(4H, OH2СN, conformer A, J 12 Hz), 5.25‒5.30 m
(4H, OH2СN, conformers B + C), 6.99‒7.02 m (2H,
HС), 7.15‒7.17 m (2H, HС). 13С NMR spectrum
(DMSO-d6), δ, ppm: 22.7, 30.0, 33.9, 85.9, 114.5,
115.7, 118.6, 128.9, 145.5 (conformer A), 22.8, 30.2,
34.2, 87.4, 114.9, 116.3, 119.0, 129.2, 144.9 (confor-
mers B + C). Found, %: C 57.40; H 6.39; Cl 11.27; N
4.43. C15H20ClNO4. Calculated, %: C 57.42; H 6.42;
Cl 11.30; N 4.46.
N,N'-[Cyclohexane-1,1-diyl(bisperoxymethane-
diyl)]di(3-chloroaniline) (12b). Yield 0.22 g (55%),
1
colorless crystals, mp 98‒99°С. H NMR spectrum
(DMSO-d6), δ, ppm: 1.33‒1.41 m (6H, H2С), 1.66‒
1.68 m (4H, H2С), 5.11‒5.13 m (4H, NСH2O), 6.64‒
6.73 m (4H, HС), 6.84‒6.85 m (2H, HС), 7.07‒7.12 m
(2H, HС). 13С NMR spectrum (DMSO-d6), δ, ppm:
22.4, 25.3, 30.5, 78.4, 109.2, 112.3, 112.8, 117.5,
130.8, 134.0, 148.5. Found, %: C 56.20; H 5.63; Cl
16.57; N 6.53%. C20H24Cl2N2O4. Calculated, %: C
56.22; H 5.66; Cl 16.59; N 6.56.
11-(4-Fluorophenyl)-8,9,13,14-tetraoxa-11-
azaspiro[6.7]tetradecane (10f). Yield 0.25 g (85%),
1
light yellow crystals, mp 79‒81°С. H NMR spectrum
(DMSO-d6), δ, ppm: 1.36‒1.58 m (8H, H2С), 1.94‒
1.99 m (2H, H2С), 2.00‒2.01 m (4H, H2С, conformer
A), 5.36 and 5.60 d (4H, OH2СN, conformer A, J 12 Hz),
5.36‒5.37 m (4H, OH2СN, conformers A + B + C),
7.09‒7.12 m (4H, HС). 13С NMR spectrum (DMSO-
d6), δ, ppm: 22.6, 29.8, 32.4, 85.9, 113.9, 115.7 d (J
17 Hz), 118.5 d (J 7 Hz), 143.7, 157.4 d (J 188 Hz,
conformer A), 22.0, 29.6, 31.1, 85.9, 113.9, 116.2 d (J
17 Hz), 120.3 d (J 7 Hz), 143.7, 157.4 d (J 188 Hz,
conformers B + C). Mass spectrum (APCI), m/z (Irel,
N,N'-[Cyclohexane-1,1-diyl(bisperoxymethane-
diyl)]di(3-fluoroaniline) (12e). Yield 0.17 g (45%),
1
colorless crystals, mp 118‒119°С. H NMR spectrum
(DMSO-d6), δ, ppm: 1.33‒1.40 m (4H, H2С), 1.66‒
1.67 m (6H, H2С), 5.10‒5.12 m (4H, NСH2O), 6.42‒
6.58 m (6H, HС), 7.09‒7.23 m (4H, HС). 13С NMR
spectrum (DMSO-d6), δ, ppm: 22.4, 25.3, 30.6, 78.5,
100.1, 104.2 d (J 17 Hz), 109.2, 109.8, 130.7 d (J 8 Hz),
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149.1, 163.6 d (J 191 Hz). Found, %: C 60.87; H 6.11;
F 9.60; N 7.07. C20H24F2N2O4. Calculated, %: C 60.90;
H 6.13; F 9.63; N 7.10.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.45‒1.48 m
(4H, H2С), 1.56‒1.64 m (4H, H2С), 1.98‒2.01 m (4H,
H2С, conformer A), 5.44 and 5.81 d (4H, OH2СN,
conformer A, J 12 Hz), 5.43‒5.46 m (4H, OH2СN,
conformers B + C), 6.71‒6.74 m (1H, HС), 6.91‒6.94
m (2H, HС), 7.26‒7.30 m (1H, HС). 13С NMR
spectrum (DMSO-d6), δ, ppm: 24.3, 33.0, 85.6 (confor-
mer A), 87.6 (conformers B + C), 103.9 d (J 20 Hz),
107.4 d (J 20 Hz), 112.6, 119.9, 130.8 d (J 8 Hz),
148.9 d (J 8 Hz), 163.3 d (J 191 Hz). Found, %: C
57.97; H 5.96; F 7.03; N 5.17. C13H16FNO4.
Calculated, %: C 57.99; H 5.99; F 7.06; N 5.20.
N,N'-[Cycloheptane-1,1-diyl(bisperoxymethane-
diyl)]di(3-chloroaniline) (13b). Yield 0.18 g (43%),
1
colorless crystals, mp 83‒84°С. H NMR spectrum
(DMSO-d6), δ, ppm: 1.39‒1.42 m (8H, H2С), 1.76‒
1.78 m (4H, H2С), 5.11‒5.12 m (4H, NСH2O), 6.65‒
6.67 m (2H, HС), 6.83‒6.84 m (2H, HС), 7.09‒7.12 m
(2H, HС), 7.20‒7.23 m (2H, HС). 13С NMR spectrum
(DMSO-d6), δ, ppm: 22.6, 30.3, 33.3, 78.3, 112.3,
112.9, 114.5, 117.5, 130.8, 134.0, 148.6. Found, %: C
57.13; H 5.91; Cl 16.03; N 6.32. C21H26Cl2N2O4.
Calculated, %: C 57.15; H 5.94; Cl 16.06; N 6.35.
10-(3-Chlorophenyl)-7,8,12,13-tetraoxa-10-aza-
spiro[5.7]tridecane (15b). Yield 0.13 g (45%), yellow
1
oil. H NMR spectrum (DMSO-d6), δ, ppm: 1.35‒1.42
N,N'-[Cycloheptane-1,1-diyl(bisperoxymethane-
diyl)]di(3-fluoroaniline) (13e). Yield 0.18 g (47%),
m (6H, H2С), 1.55‒1.64 m (4H, H2С), 1.84‒1.85 m
(4H, H2С, conformer A), 5.35 and 5.84 d (4H, OH2СN,
conformer A, J 12 Hz), 5.39‒5.44 m (4H, OH2СN,
conformers B + C), 6.94‒6.99 m (1H, HС), 7.01‒7.06
m (1H, HС), 7.14‒7.15 m (1H, HС), 7.26‒7.30 m (1H,
HС). 13С NMR spectrum (DMSO-d6), δ, ppm: 22.7,
25.1, 30.0, 85.4 108.9, 115.2, 116.3, 120.7, 130.9,
134.0, 148.3 (conformer A); 22.8, 24.9, 29.4, 87.7
111.0, 115.9, 117.1, 121.5, 131.3, 134.0, 148.3
(conformers B + C). Mass spectrum (APCI), m/z (Irel,
%): 243 (45) [C8H8ClNO3 + H + CH3CN]+, 238 (12)
[C7H6ClNO + H+ 2CH3CN]+, 202 (14) [C8H8ClNO3 +
H]+, 197 (100) [C7H6ClNO + H + CH3CN]+, 181 (67)
[C7H6ClN + H + CH3CN]+, 156 (18) [C7H6ClNO + H]+,
140 (47) [C7H6ClN+H]+. Found, %: C 56.07; H 6.02;
Cl 11.80; N 4.62. C14H18ClNO4. Calculated, %: C
56.10; H 6.05; Cl 11.83; N 4.67.
1
light yellow oil. H NMR spectrum (DMSO-d6), δ,
ppm: 1.39‒1.47 m (4H, H2С), 1.59‒1.63 m (4H, H2С),
1.75‒1.76 m (4H, H2С), 5.09‒5.12 m (4H, NСH2O),
6.40‒6.44 m (2H, HС), 6.54‒6.58 m (2H, HС), 7.08‒
7.13 m (2H, HС), 7.20‒7.22 m (2H, HС). 13С NMR
spectrum (DMSO-d6), δ, ppm: 22.6, 30.2, 33.2, 78.4,
100.1, 104.1 d (J 17 Hz), 109.7, 114.4 d (J 20 Hz), 130.7
d (J 9 Hz), 149.7 d (J 8 Hz), 163.7 d (J 190 Hz). Found,
%: C 61.73; H 6.39; F 9.27; N 6.83. C21H26F2N2O4.
Calculated, %: C 61.75; H 6.42; F 9.30; N 6.86.
9-(3-Chlorophenyl)-6,7,11,12-tetraoxa-9-aza-
spiro[4.7]dodecane (14b). Yield 0.15 g (56%),
1
colorless crystals, mp 70‒71°С. H NMR spectrum
(DMSO-d6), δ, ppm: 1.45‒1.48 m (4H, H2С), 1.56‒
1.63 m (4H, H2С), 1.98‒2.01 m (4H, H2С, conformer A),
5.44 and 5.81 d (4H, OH2СN, conformer A, J 12 Hz),
5.43‒5.46 d (4H, OH2СN, conformers B + C), 6.95‒
6.99 m (1H, HС), 7.05‒7.07 m (1H, HС), 7.15‒7.16 m
(1H, HС), 7.26‒7.29 m (1H, HС). 13С NMR spectrum
(DMSO-d6), δ, ppm: 24.3, 33.0, 85.6 (conformer A),
87.6 (conformers B + C), 115.4, 116.6, 119.9, 120.0,
130.9, 134.0, 148.4. Mass spectrum (APCI), m/z (Irel, %):
286 (17) [M + H]+, 243 (81) [C8H8ClNO3 + H +
CH3CN]+, 238 (14) [C7H6ClNO + H + 2CH3CN]+, 202
(37) [C8H8ClNO3 + H]+, 197 (100) [C7H6ClNO + H +
CH3CN]+, 190 (22) [C7H6ClNO + Cl]¯, 181 (93)
[C7H6ClN + H + CH3CN]+, 156 (19) [C7H6ClNO + H]+,
154 (100) [C7H6ClNO – H]¯, 140 (53) [C7H6ClN + H]+.
Found,%: C 54.63; H 5.62; Cl 12.39; N 4.87.
C13H16ClNO4. Calculated, %: C 54.65; H 5.64; Cl
12.41; N 4.90.
10-(3-Fluorophenyl)-7,8,12,13-tetraoxa-10-aza-
spiro[5.7]tridecane (15e). Yield 0.15 g (55%), light
yellow powder, mp 48‒49°С. 1H NMR spectrum
(DMSO-d6), δ, ppm: 1.35‒1.44 m (6H, H2С), 1.55‒
1.66 m (4H, H2С), 1.84‒1.85 m (4H, H2С, conformer
A), 5.36 and 5.83 d (4H, OH2СN, conformer A, J 12 Hz),
5.39‒5.44 m (4H, OH2СN, conformers B + C), 6.70‒
6.77 m (1H, HС), 6.88‒6.94 m (2H, HС), 7.26‒7.32 m
(1H, HС). 13С NMR spectrum (DMSO-d6), δ, ppm:
21.7, 25.1, 30.1, 85.3, 103.6 d (J 21 Hz), 107.3 d (J
17 Hz), 108.8, 112.4, 130.8 d (J 8 Hz), 148.9, 163.3 d
(J 197 Hz, conformer A); 22.7, 24.9, 29.4, 87.6, 103.6
d (J 21 Hz), 107.3 d (J 17 Hz), 108.8, 113.2, 130.8 d (J
8 Hz), 148.9, 163.3 d (J 197 Hz, conformers B + C).
Mass spectrum (APCI), m/z (Irel, %): 284 (7) [M + H]+,
227 (56) [C8H8FNO3 + H + CH3CN]+, 186 (40)
[C8H8FNO3 + H]+, 181 (100) [C7H6FNO + H +
CH3CN]+, 165 (71) [C7H6FN + H + CH3CN]+, 140 (32)
9-(3-Fluorophenyl)-6,7,11,12-tetraoxa-9-azaspiro-
[4.7]dodecane (14e). Yield 0.13 g (50%), yellow oil.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

631
[C7H6FNO + H]+, 124 (50) [C7H6FN + H]+. Found, %:
C 59.34; H 6.38; F 6.68; N 4.91. C14H18FNO4.
Calculated, %: C 59.36; H 6.40; F 6.71; N 4.94.
The APCI mass spectra were registered at the Khimiya
Center for Collective Use, Ufa Research Center,
Russian Academy of Sciences.
11-(3-Chlorophenyl)-8,9,13,14-tetraoxa-11-aza-
spiro[6.7]tetradecane (16b). Yield 0.17 g (57%), light
yellow powder, mp 60‒61°С. 1H NMR spectrum
(DMSO-d6), δ, ppm: 1.35‒1.48 m (8H, H2С), 1.55‒
1.56 m (4H, H2С), 1.92‒2.00 m (4H, H2С, conformer
A), 5.34 and 5.79 d (4H, OH2СN, conformer A, J 12 Hz),
5.37‒5.41 m (4H, OH2СN, conformers B + C), 6.94‒
6.96 m (1H, HС), 7.03‒7.05 m (1H, HС), 7.13‒7.14 m
(1H, HС), 7.25‒7.29 m (1H, HС). 13С NMR spectrum
(DMSO-d6), δ, ppm: 22.7, 29.8, 32.4, 85.1 115.2,
116.4, 120.7, 130.9, 134.0, 136.3, 148.04. Mass
spectrum (APCI), m/z (Irel, %):243 (61) [C8H8ClNO3 +
H + CH3CN]+, 238 (17) [C7H6ClNO + H + 2CH3CN]+,
202 (23) [C8H8ClNO3 + H]+, 197 (100) [C7H6ClNO +
H + CH3CN]+, 181 (66) [C7H6ClN + H + CH3CN]+, 156
(12) [C7H6ClNO + H]+, 154 (23) [C8H8ClN + H]+, 140
(39) [C7H6ClN + H]+. Found, %: C 57.39; H 6.39; Cl
11.27; N 4.44. C15H20ClNO4. Calculated, %: C 57.42;
H 6.42; Cl 11.30; N 4.46.
FUNDING
The work was financially supported by the Russian
Foundation of Basic Research (project no. 16-29-
10687 ofi_m).
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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