Efficient synthesis of 3-aryl(hetaryl)-1,5,3-dioxazepanes involving catalysts containing Sm and Co

Article abstract of DOI:10.1134/S1070428013050217

Efficient synthetic procedure was developed for 3-aryl(hetaryl)-1,5,3- dioxazepanes consisting in the transamination of 3-tert-butyl-1,5,3-dioxazepane with arylamines and also by the reaction of 1,2-ethanediol with N,N-bis(methoxymethyl)aryl(hetaryl)amine

Full text of DOI:10.1134/S1070428013050217

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 5, pp. 750−753. © Pleiades Publishing, Ltd., 2013.
Original English Text © N.N. Makhmudiyarova, K.I. Prokof’ev, L.V. Mudarisova, A.G. Ibragimov, U.M. Dzhemilev, 2013, published in Zhurnal Organicheskoi
Khimii, 2013, Vol. 49, No. 5, pp. 767−770.
Efficient Synthesis of 3-Aryl(hetaryl)-1,5,3-dioxazepanes
Involving Catalysts Containing Sm and Co
N. N. Makhmudiyarova, K. I. Prokof’ev, L. V. Mudarisova,
A. G. Ibragimov, and U. M. Dzhemilev
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia
е-mail: ink@anrb.ru
Received July 4, 2012
Abstract—Efficient synthetic procedure was developed for 3-aryl(hetaryl)-1,5,3-dioxazepanes consisting in the
transamination of 3-tert-butyl-1,5,3-dioxazepane with arylamines and also by the reaction of 1,2-ethanediol with
N,N-bis(methoxymethyl)aryl(hetaryl)amines in the presence of catalytic amounts of Sm and Co compounds.
DOI: 10.1134/S1070428013050217
Oxazepane derivatives are widely used in the medicine
as substances exhibiting analgesic, antipyretic, sedative
[1, 2], anticancer [3], and fungicidal [4, 5] action. Quite
a number of papers treats the problems of the synthesis
of O,N-containing five- and six-membered heterocycles
[6–8], whereas scarce information exist on the selective
synthesis of N-substituted 1,5,3-dioxazepanes [9–11].
N-Alkyl(cycloalkyl, benzyl)-1,5,3-dioxazepanes are ob-
tained by heating alkyl(cycloalkyl, benzyl)amines with
paraformaldehyde and 1,2-ethylene glycol in aromatic
solvents [9–11]. To the time of the start of our study
no literature data existed on the selective synthesis of
3-aryl(hetaryl)-1,5,3-dioxazepanes.
chloroform) afforded 3-phenyl-1,5,3-dioxazepane (Iа)
in less than 8% yield. The yield of compound Ia may
be increased if the transamination is carried out in the
presence of catalysts based on the salts and complexes
of Cu, Pd, Co, Zr, Ti, Hf, V, Fe, Sm [12], where the most
active are Sm(NO3)3·6H2O and CoCl2. Under the action of
these catalysts (5 mol%, ~20°С, 3 h, solvent CHCl3) the
transamination proceeds highly selectively (~100%) with
the formation of N-phenyl-1,5,3-dioxazepane (Iа) in 70
and 65% yields respectively. The significant acceleration
of the reaction is apparently due to the coordination of the
nitrogen atom of the molecule of the initial 3-tert-butyl-
1,5,3-dioxazepane to the central atom of the catalyst [13].
The probable route [14, 15] of the catalytic
transamination of 3-tert-butyl-1,5,3-dioxazepane under
the аction of aniline involves a stage of the opening of
the initial heterocycle, the nucleophilic addition of ani-
line to the carbocation and the intramolecular cyclization
affording 3-phenyl-1,5,3-dioxazepane (Iа) (Scheme 1).
In the 1Н NMR spectrum of compound Ia the proton
signals appear as narrow singlets in the region of 4.80
(Н2,4) and 3.08 ppm (Н6,7) indicating the fast ring inver-
sion in the NMR time scale. In the 13С NMR spectrum
the dioxazepane carbon atoms give rise to signals δ 54.92
and 35.78 ppm.
By the analogy of the previously investigated
transamination of 3-methyl-1,3,5-dithiazinane with ani-
line giving 3-phenyl-1,3,5- dithiazinane [12], we carried
out the reaction of primary arylamines with 3-tert-butyl-
1,5,3-dioxazepane in the presence of catalysts based on
transition and rare earth metals presuming the possibility
of the replacement of the nitrogen atom in the molecule
of 3-tert-butyl-1,5,3-dioxazepane by the transamination
leading to the formation of the corresponding 3-aryl-
1,5,3-dioxazepanes in the presence of catalytic amounts
of Sm and Co complexes.
Preliminary experiments have shown that noncata-
lytic reaction of aniline with an equimolar quantity of
3-tert-butyl-1,5,3-dioxazepane (~20°С, 3 h, solvent
The structure of the initial arylamine does not consid-
erably affect the yield of of compound I. In the reaction of
750

EFFICIENT SYNTHESIS OF 3-ARYL(HETARYL)-1,5,3-DIOXAZEPANES
751
Scheme 1.
..
+
O
PhNH2
O
O
O
O
O
O
O
O
O
+
_XH2
+
X
CH2
..
CH2
N
X
X
NH
Ph
NH
Ph
Ia
[M]
[M]
[M]
Ph
X = t-BuN; [M] = Sm(NO3)3·6H2O, CoCl2.
Scheme 2.
O
O
O
[M]
]
+
N
NH2
N
_
]
NH2
R
R
O
Iа_Ii
R = H (a), m-СН3 (b), p-СН3 (c), о-ОСН3 (d), m-ОСН3 (e), p-ОСН3 (f), о-NO2 (g), m-NO2 (h), p-NO2 (i); [M] =
Sm(NO3)3·6H2O, CoCl2.
o-, m-, and p-nitro-, o-, m-, and p-methoxy-, and also m-
and p-methylanilines with equimolar quantity of 3-tert-
butyl-1,5,3-dioxazepane (5 mol% of Sm(NO3)3·6H2O,
~20°С, 3 h) the corresponding 3-aryl-1,5,3-dioxazepanes
Iа–Ii were formed in 60–70% yields (Scheme 2).
С,Н- and S,Н-acids with alkoxymethylamines results
in acyclic amines and aminosulfides due to the forma-
tion of С–С and С–S bonds [16], it is expectable that
the aminomethylation of 1,2-ethanediol with N,N-bis-
(alkoxymethyl)amines would lead to the corresponding
dioxazepanes by the simultaneous formation of two С–О
bonds. The performed experiments showed that under the
The attempt to transaminate the 3-tert-butyl-
1,5,3-dioxazepane with hetarylamines (3-amino-5-
methylisoxazole, 2-amino-, 3-amino-, 2-amino-4-
methyl-, 2-aminoо-5-methylpyridine) failed.
.
chosen conditions [5 mol% of Sm(NO3)3 6H2O, 20°С,
0.5 h] only N,N-bis(methoxymethyl)-N-hetarylamines
prepared from 3-amino-5-methylisoxazole and 2-amino-
5-methylpyridine readily reacted with 1,2-ethanediol to
give selectively 3-hetaryl-1,5,3-dioxazepanes IIa, IIb in
60 and 64% yields (Scheme 3). Compounds IIa, IIb are
To develop an efficient synthetic procedure for
3-hetaryl-1,5,3-dioxazepanes we examined the reac-
tion of 1,2-ethanediol with N,N-bis(methoxymethyl)-
N-hetarylamines. Whereas the aminomethylation of
Scheme 3.
OСH3
OСH3
OСH3
Ht
N
N
R
OСH3
( )n
HO
OH
[M] _2MeOH
O
_2MeOH
O
[M]
( )n
Ht
N
N
O
R
O
Iа_Ii, n = 1
IIIa, n = 2
IIа, IIb
CH3
(b);
II, Ht =
(a),
N
H3C
O
R = H (a), m-СН3 (b), p-СН3 (c), о-ОСН3 (d), m-ОСН3 (e), p-ОСН3 (f), о-NO2 (g), m-NO2 (h), p-NO2 (i); [M] =
Sm(NO3)3·6H2O for Iа–Ii, IIа,IIb, zeolites 0.96 HY-BS for IIIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

MAKHMUDIYAROVA et al.
752
not formed without catalyst.
and 10 mmol of an appropriate arylamine was added, and
the stirring was continued for 3 h at room temperature
(~20°С).
Thedevelopedprocedureofthecycloaminomethylation
of ethylene glycol with N,N-bis(methoxy-methyl)
hetarylamines made it possible to extend this reaction
to N,N-bis(methoxymethyl)-N-arylamines (aryl = Ph,
m- and p-methyl-, o-, m-, and p-methoxy-, o-, m-, and
p-nitrophenyl) and to obtain N-aryl-1,5,3- dioxazepanes
Ia–Ii in 80–89% yields (Scheme 3). We attempted
to try this procedure for a selective synthesis of di-
oxazocanes and dioxazonanes by the reaction of N,N-
bis(methoxymethyl)-N-arylamines with 1,3-propanediol
and 1,4-butanediol, and only in the presence of zeolites of
the grade 0.96НY-BS (5 wt%) N,N-bis(methoxymethyl)-
N-phenylamine reacted with 1,3-propanediol in CHCl3
at ~60°С furnishing 3-phenyl-1,5,3-dioxazocane (IIIa)
in 40% yield (Scheme 3).
b. Reaction of N,N-bis(methoxymethyl)-N-
arylamines with 1,2-ethanediol. Into a Schlenk vessel
placed on a magnetic stirrer was charged in an argon
flow 10 mmol of N,N-bis(methoxymethyl)-N-aryl-amine
[17] and 10 mmol of 1,2-ethanediol at room tempera-
ture (~20°С), 5 ml of chloroform, 0.5 mmol of catalyst
.
Sm(NO3)3 6H2O was added, the mixture was stirred for
30 min.
3-Phenyl-1,5,3-dioxazepane (Iа). Yield 70% (а),
1
80% (b), mp 177–178°С. Н NMR spectrum, δ, ppm:
3.08 s (4Н, СН2), 4.80 s (4Н, СН2), 6.91–7.35 m (4Н,
СН). 13С NMR spectrum, δ, ppm: 35.78 (С6,7), 54.92
(С2,4), 115.93 (С9,13), 119.95 (С11), 129.30 (С10,12), 145.83
(С8). Mass spectrum, m/z (Irel, %): 179 [M]+ (100), 159
[C9H13NО]+ (30), 104 [C4H10О2]+ (15), 92 [C6H6N]+
(45), 77 [C6H5]+ (95).
Thus our research resulted in the development of
anefficientsynthesisof3-aryl(hetaryl)-1,5,3-dioxazepanes
by transamination of 3-tert-butyl-1,5,3-dioxazepane
with arylamins and also by cycloaminomethylation
of 1,2-ethanediol with N,N-bis(methoxy-methyl)
aryl(hetaryl)amines under mild conditions in high yield
and selectivity in the presence of catalysts based on Sm
and Co compounds.
3-(3-Methylphenyl)-1,5,3-dioxazepane (Ib). Yield
1
64% (а), 61% (b), mp 173–174°С. Н NMR spectrum,
δ, ppm: 2.65 s (3Н, СН3), 3.88 s (4Н, СН2), 4.89 s (4Н,
СН2), 6.70–7.28 m (4Н, СН). 13С NMR spectrum, δ,
ppm: 21.33 (С14), 62.29 (С6,7), 82.90 (С2,4), 108.98
(С13), 113.66 (С9), 120.56 (С11), 129.97 (С10), 147.48
(С12), 148.93 (С8). Mass spectrum, m/z (Irel, %): 193 [M]+
(40), 180 [C10H15NO2]+ (15), 136 [C8H10NO]+ (37), 106
[C7H8N]+ (100), 104 [C4H10О2]+ (15), 92 [C6H7]+ (32),
77 [C6H5]+ (54).
EXPERIMENTAL
The reaction progress was monitored byTLC on Silufol
W-254 plates, eluent petroleum–ether EtOAc–CHCl3, 5 :
1 : 1. The reaction products were analyzed by HPLC on
a chromatograph Altex-330 (USA) equipped with a UV
detector at the wavelength 340 nm. 1Н and 13С NMR spec-
tra were registered on a spectrometer BrukerAvance 400
(100.62 and 400.13 MHz respectively), solvent CDCl3.
GC-MS measurements were carried out on instruments
Finnigan-4021 (glass capillary column 5000 × 0.25 mm,
stationary phase НР-5, carrier gas helium, ramp from
50 to 300°С at a rate 5 deg/min, vaporizer tempera-
ture 280°С, ion source temperature 250°С, 70 eV) and
Shimadzu QP-2010 Plus (capillary column Supelco PTE-5
3-(4-Methylphenyl)-1,5,3-dioxazepane (Ic). Yield
1
60% (а), 65% (б), mp 138–139°С. Н NMR spectrum,
δ, ppm: 2.36 s (3Н, СН3), 3.87 s (4Н, СН2), 4.44 s (4Н,
СН2), 6.75–7.23 m (4Н, СН). 13С NMR spectrum, δ, ppm:
21.34 (С14), 67.34 (С6,7), 83.22 (С2,4), 114.22 (С9,13),
120.18 (С10,12), 141.46 (С11), 147.55 (С8).
3-(2-Methoxyphenyl)-1,5,3-dioxazepane (Id).
1
Yield 63% (а), mp 118–119°С. Н NMR spectrum, δ,
ppm: 3.53–3.79 m (7Н, СН2, СН3), 4.94 s (4Н, СН2),
6.37–7.23 m (4Н, СН). 13С NMR spectrum, δ, ppm:
55.23 (С15), 68.77 (С6,7), 80.88 (С2,4), 102.01 (С10),
104.98 (С13), 109.21 (С12), 130.06 (С11), 146.93 (С8),
160.61 (С9). Mass spectrum, m/z (Irel, %): 209 [M]+
(5), 196 [C10H14NO3]+ (5), 166 [C9H12NO2]+ (21), 122
[C7H8NO]+ (31), 107 [C7H14NO)]+ (23), 104 [C4H10О2]+
(100), 77 [C6H5]+ (58).
30 m
× 0.25 mm). For column chromatography silica gel
KSK (100–200 μm) was utilized.
3-Aryl-1,5,3-dioxazepanes. а. Transamination of
3-tert-butyl-1,5,3-dioxazepane with arylamines. Into a
Schlenk vessel placed on a magnetic stirrer was charged in
an argon flow 10 mmol of 3-tert-butyl-1,5,3-dioxazepane
.
[9] and 0.5 mmol of catalyst Sm(NO3)3 6H2O or CoCl2,
3-(3-Methoxyphenyl)-1,5,3-dioxazepane (Ie). Yield
67 (а), 81% (b), mp 122–124°С. 1Н NMR spectrum, δ,
the mixture was stirred for 30 min, 5 ml of chloroform
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013

EFFICIENT SYNTHESIS OF 3-ARYL(HETARYL)-1,5,3-DIOXAZEPANES
753
ppm: 3.47–3.82 m (7Н, СН2, СН3), 4.87 s (4Н, СН2),
ACKNOWLEDGMENTS
6.28–7.15 m (4Н, СН). 13С NMR spectrum, δ, ppm: 55.14
(С15), 69.40 (С6,7), 80.66 (С2,4), 102.18 (С9), 105.46 (С11),
108.33 (С13), 129.78 (С12), 147.80 (С8), 158.26 (С10).
The study was carried out under the financial support
of the Russian Foundation for Basic Research (grants nos.
11-03-00101-а, 11-03-97011-р_Volga region_а).
3-(4-Methoxyphenyl)-1,5,3-dioxazepane (If). Yield
1
62% (а), 80% (b), mp 129–130°С. Н NMR spectrum,
REFERENCES
δ, ppm: 3.43–3.70 m (7Н, СН2, СН3), 4.87 s (4Н, СН2),
6.40–7.28 m (4Н, СН). 13С NMR spectrum, δ, ppm: 59.89
(С15), 73.83 (С6,7), 81.07 (С2,4), 112.66 (С10,12), 129.92
(С9,13), 146.74 (С8), 160.69 (С11).
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3-(2-Nitrophenyl)-1,5,3-dioxazepane (Ig). Yield
64% (а), 60% (b), mp 140–143°С. 1Н NMR spectrum, δ,
ppm: 3.69 m (4Н, СН2), 5.27 s (4Н, СН2), 7.31–7.83 m
(4Н, СН). 13С NMR spectrum, δ, ppm: 68.27 (С6,7),
79.30 (С2,4), 109.10 (С10), 114.07 (С13), 120.56 (С12),
129.75 (С11), 147.02 (С8), 149.09 (С9). Mass spectrum,
m/z (Irel, %): 224 [M]+ (60), 195 [C9H11N2O3]+ (50),
151 [C7H7N2O2]+ (100), 137 [C6H5N2O2]+ (15), 104
[C4H10О2]+ (35), 77 [С6Н5]+ (23).
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3-(3-Nitrophenyl)-1,5,3-dioxazepane (Ih). Yield
69% (а), 77% (b), mp 133–134°С. 1Н NMR spectrum, δ,
ppm: 3.78 m (4Н, СН2), 5.04 s (4Н, СН2), 7.24–7.90 m
(4Н, СН). 13С NMR spectrum, δ, ppm: 69.52 (С6,7), 80.16
(С2,4), 109.95 (С9), 114.35 (С11), 121.17 (С13), 129.02
(С12), 147.48 (С8), 148.51 (С10).
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3-(4-Nitrophenyl)-1,5,3-dioxazepane (Ii). Yield
66% (а), 59% (b), mp 156–157°С. 1Н NMR spectrum, δ,
ppm: 3.54 m (4Н, СН2), 4.97 s (4Н, СН2), 7.38–7.90 m
(4Н, СН). 13С NMR spectrum, δ, ppm: 71.05 (С6,7),
82.62 (С2,4), 109.60 (С10,12), 128.93 (С9,13), 146.98 (С8),
149.20 (С9).
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3-(5-Methylisoxazol-3-yl)-1,5,3-dioxazepane (IIа).
Yield 60% (b). 1Н NMR spectrum, δ, ppm: 2.14 m (3Н,
СН3), 3.54 d (4Н, СН2, J 4Hz), 5.43 s (4Н, СН2), 7.36 s
(1Н, СН). 13С NMR spectrum, δ, ppm: 15.13 (С13), 68.25
(С6,7), 86.30 (С2,4), 89.17 (С12), 140.72 (С8), 165.60 (С11).
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3-(5-Methylpyridin-2-yl)-1,5,3-dioxazepane (IIb).
Yield 64% (b). 1Н NMR spectrum, δ, ppm: 2.18 s (3Н,
СН3), 3.22 d (4Н, СН2, J 4.4 Hz), 5.35 s (4Н, СН2),
7.16–7.20 m (3Н, СН). 13С NMR spectrum, δ, ppm: 20.17
(С14), 71.03 (С6,7), 87.15 (С2,4), 101.30 (С13), 119.20
(С11), 128.26 (С12), 140.40 (С10), 151.91 (С8).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 5 2013