Cyclization of vinyl ethers derived from amino alcohols

Article abstract of DOI:10.1134/S1070428007070044

Cyclization of vinyl ethers derived from linear and cyclic α- and β-amino alcohols, catalyzed by mercury(II) acetate gave 2-methyloxazolidines and 2-methylperhydro-1,3-oxazines in 37-94% yield.

Full text of DOI:10.1134/S1070428007070044

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 7, pp. 966–969. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © B.F. Kukharev, V.K. Stankevich, G.R. Klimenko, V.A. Kukhareva, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43,
No. 7, pp. 973–976.
Cyclization of Vinyl Ethers Derived from Amino Alcohols
B. F. Kukharev, V. K. Stankevich, G. R. Klimenko, and V. A. Kukhareva
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: irk_inst_chem@irioch.irk.ru
Received July 21, 2006
Abstract—Cyclization of vinyl ethers derived from linear and cyclic α- and β-amino alcohols, catalyzed by
mercury(II) acetate gave 2-methyloxazolidines and 2-methylperhydro-1,3-oxazines in 37–94% yield.
DOI: 10.1134/S1070428007070044
It is known that 2-vinyloxyalkanamines are capable
of undergoing cyclization to 2-methyloxazolidines. On
the basis of the available published data we can judge
only on the effect of substituents on the nitrogen atom
on this reaction. For example, various N-acyl deriva-
tives of 2-vinyloxyethanamine readily undergo cycliza-
tion either by the action of protic acids [1] or on
heating [2]. The cyclization of 2-(alkyl- and aryl-
amino)alkanols successfully occurs only in the pres-
ence of soft acids (such as Hg or Pd ) [3, 4]. There
are no published data on the effect of the fragment
connecting the amino and vinyloxy groups on the
cyclization of vinyloxyalkanamines.
The reactions were carried out according to the proce-
dure described in [4], i.e., by heating in benzene in the
presence of 0.3 mol % of mercury(II) acetate. As we
showed previously [3, 4], the cyclization of 2-vinyl-
oxyethanamine gives 2-methyloxazolidine like A
which undergoes ring–chain tautomeric transformation
into 2-ethylideneaminoethanol B; exchange reaction of
the latter with initial 2-vinyloxyethanamine leads to
the formation of N-ethylidene-2-vinyloxyethanamine
as the major product (yield 50%), while the yield of
2-methyloxazolidine is as poor as 20%.
2
+
2+
It is known that introduction of a substituent into
the bridging fragment increases the concentration of
cyclic isomer in ring–chain tautomeric systems [5].
Therefore, we anticipated that cyclization of 2-vinyl-
oxypropan-1-amine (Ia) and 1-vinyloxy-2-methylpro-
pan-2-amine (Ib) will produce the corresponding oxa-
zolidines IIa and IIb in higher yields than in the
cyclization of 2-vinyloxyethanamine (Scheme 1). In
In the present work we examined the cyclization of
α- and β-vinyloxy-substituted acyclic and cyclic ali-
phatic amines with a view to elucidate how the nature
of the linking unit affects the cyclization process and
estimate preparative potential of this reaction for the
synthesis of 2-methylperhydro-1,3-oxazacycloalkanes.
Scheme 1.
R'
R
R'
R'
R
R'
NH2
R'
R
R'
N
H C
2
O
HO
O
NH
Me
Me
Ia, Ib
A
IIa, IIb
B
R'
R'
R'
R
R'
Ia, Ib
H C
2
O
HO
+
N
Me
NH2
R
IIIa, IIIb
IVa, IVb
R = Me, R′ = H (a); R = H, R′ = Me (b).
966

CYCLIZATION OF VINYL ETHERS DERIVED FROM AMINO ALCOHOLS
967
fact, the expected products IIa and IIb were obtained
in 37 and 83% yield, respectively. The yield of Schiff
base IIIa was 31%, and that of IIIb, only 2%. Presum-
ably, considerable increase in the yield of cyclic
product IIb, as compared to the cyclization products
obtained from 2-vinyloxyethanamine and 2-vinyloxy-
propan-1-amine (Ia), results from the gem-dialkyl
effect [5].
The structure of the isolated compounds was con-
firmed by the IR and H NMR spectra. The IR spectra
of IIa, IIb, VI, VIII, and Xa–Xc contained no absorp-
1
tion bands typical of vinyloxy group in the initial vinyl
–
1
ethers (1605, 1620 cm ), but bands in the regions
–
1
1080–1114, 1116–1139, and 1149–1185 cm were
present due to vibrations of the O–C–N fragment [7].
1
The H NMR spectra of these compounds lacked
olefinic proton signals, and protons in the NCH(CH )O
fragment resonated as a quartet at δ 3.84–4.66 ppm and
3
As a rule, increased rigidity of the linking fragment
favors formation of the cyclic product [5]. We syn-
thesized vinyl ethers of cyclic amino alcohols (com-
pounds V and VII) containing exo- or endocyclic
nitrogen atom and brought them into cyclization in the
presence of mercury(II) acetate. The yields of fused
oxazolidines VI and VIII were 89–91%, i.e., they were
larger by 3–15% than in the cyclization of vinyl ethers
derived from acyclic N-methyl α-amino alcohols [4]
a doublet at δ 1.23–1.33 ppm.
1
The H NMR spectrum of the isomerization product
of 2-vinyloxypropan-1-amine (Ia) was more com-
plicated. It contained multiplets at δ 1.18, 1.32, and
4
.60 ppm due to protons in the methyl groups in
positions 5 and 2 of the oxazolidine ring (cis and trans
isomers) and OCHN proton (structure A), respectively.
In addition, there was a doublet at δ 1.97 ppm (N=CH)
(
Scheme 2). We failed to effect analogous cyclization
and a quartet at δ 7.72 ppm (N=CHCH ) belonging to
3
of 2-vinyloxyamiline: the reaction was accompanied
by strong tarring, and distillation of the reaction mix-
ture gave 91% of o-aminophenol. This result resembles
unsuccessful attempts [6] to obtain acetals by addition
of alcohols to 2-vinyloxyaniline in the presence of
protic or Lewis acids, where o-aminophenol and poly-
meric products were also formed.
structure B. In keeping with the signal intensities, the
reaction gives an equimolar mixture of cis and trans
isomers of oxazolidine IIa. The fraction of imino
alcohol B was estimated at 21% on the basis of the
intensities of the N=CH and OCHN signals and signals
from methyl protons of tautomers A and B.
Thus the results of our study show that the cycliza-
tion of vinyl ethers derived from amino alcohols fol-
lows general relations found for the effect on such re-
actions of the fragment connecting the ether and amino
groups and that this reaction may be used to synthesize
Scheme 2.
O
CH
2
O
N
Me
NHMe
1
,3-oxazacycloalkanes having various structures.
Me
V
VI
EXPERIMENTAL
1
The H NMR spectra were recorded at 30°C on
O
O
CH
2
N
a Jeol FX 90Q spectrometer at 90 MHz using HMDS
as internal reference. The IR spectra were measured on
a Specord 75 IR spectrophotometer from samples pre-
pared as thin films (neat). The purity of the products
was checked, and the reaction mixtures were analyzed,
by GLC on an LKhM-80 chromatograph equipped
with a thermal conductivity detector and a steel
column, 3000×3 mm, packed with 3% of OV-17 on
Inerton Super (0.160–0.200 mm); carrier gas helium,
oven temperature programming from 50 to 250°C at
a rate of 4 deg/min.
N
H
Me
VII
VIII
The cyclization of 3-vinyloxypropan-1-amines
IXa–IXc smoothly afforded the corresponding 2-meth-
ylperhydro-1,3-oxazines Xa–Xc in 67–94% yield
(
Scheme 3).
Scheme 3.
R
N
H C
2
O
NHR
2-Methylperhydro-1,3-oxazacycloalkanes (gen-
eral procedure). A mixture of 0.1 mol of the corre-
sponding vinyl ether and 0.005 mol of mercury(II)
acetate in 50 ml of benzene was heated under reflux
with stirring. Samples of the reaction mixture were
O
Me
IXa–IXc
Xa–Xc
R = H (a), NCCH
2 2 2
CH (b), PhCH (c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

9
68
KUKHAREV et al.
withdrawn intermittently and analyzed by GLC. When
the initial vinyl ether disappeared, the mixture was
subjected to fractional distillation under reduced
pressure.
H 10.51; N 9.71. C
H 10.71; N 9.92.
H15NO. Calculated, %: C 68.04;
8
2
,3-Dimethylperhydro-1,3-benzoxazole (VI).
20 20
Yield 89%, bp 77–79°C (20 mm), d = 0.9563, n =
1.4658. IR spectrum, ν, cm : 805, 817, 885, 923,
1000, 1075, 1100, 1120, 1140, 1180, 1200, 1315, 1330,
1345, 1365, 1440, 2755, 2840, 2920. H NMR spec-
4
D
–
1
2
,5-Dimethyloxazolidine (IIa, A) and 1-ethyli-
deneaminopropan-2-ol (IIa, B). Yield 37%, bp 49–
2
0
20
1
5
2°C (80 mm), d = 0.9529, nD = 1.4350. IR spec-
4
–1
3
trum, ν, cm : 650, 795, 845, 905, 935, 1075, 1130,
180, 1290, 1325, 1365, 1425, 1670, 2865, 2920, 2965,
250, 3360. H NMR spectrum, δ, ppm: A: 1.18 m
trum, δ, ppm: 1.31 d (3H, CH
1.82 m (8H, CH
3
, J = 4.7 Hz), 1.32–
1
3
2
), 2.25 s (3H, CH
3
), 2.35 m (1H,
1
3
3a-H), 3.42 m (1H, 7a-H), 3.98 q (1H, 2-H, J =
4.7 Hz). Found, %: C 69.52; H 11.12; N 8.95.
(
3H, 5-CH ), 1.32–1.33 m (3H, 2-CH ), 2.70 m and
3
3
3.33 m (2H, 4-H), 3.96 m (1H, 5-H), 4.60 m (1H, 2-H),
C H17NO. Calculated, %: C 69.63; H 11.04; N 9.02.
9
4
.73 br.s (1H, NH); B: 1.20 m (3H, CH CHO), 1.97 d
2-Methylperhydro[1,3]oxazolo[3,4-a]pyridine
3
3
20
(
3H, N=CHCH , J = 4.4 Hz), 3.40 m (2H, NCH ),
(VIII). Yield 91%, bp 90–91°C (50 mm), d = 0.9637,
3
2
4
2
0
–1
3
.99 m (1H, OCH), 4.73 br.s (1H, OH), 7.72 q (1H,
n = 1.4675. IR spectrum, ν, cm : 600, 655, 675, 780,
D
3
N=CH, J = 4.4 Hz). Found, %: C 59.24; H 10.85;
N 13.68. C H NO. Calculated, %: C 59.37; H 10.96;
N 13.85.
820, 840, 850, 910, 930, 975, 1000, 1075, 1100, 1115,
1160, 1200, 1230, 1260, 1295, 1305, 1330, 1385, 1400,
5
11
1
1440, 2790, 2810, 2875, 2930. H NMR spectrum, δ,
3
2
,4,4-Trimethyloxazolidine (IIb). Yield 83%,
ppm: 1.24 d (3H, CH
3
, J = 4.9 Hz), 1.74–2.11 m (6H,
2
0
20
bp 39–43°C (45 mm), d = 0.9021, n = 1.4270. IR
spectrum, ν, cm : 590, 650, 805, 890, 985, 1010,
1
2
6-H, 7-H, 8-H), 2.65 m (3H, 5-H, 8a-H), 3.43 m (2H,
4
D
–
1
3
1-H), 3.87 q (1H, 3-H, J = 4.9 Hz). Found, %:
055, 1120, 1135, 1180, 1220, 1305, 1375, 1435, 2850,
C 68.28; H 10.84; N 9.71. C
8
H15NO. Calculated, %:
1
930, 2955, 3280. H NMR spectrum, δ, ppm: 1.21 s
C 68.04; H 10.71; N 9.92.
(
3H, 4-CH ), 1.25 s (3H, 4-CH ), 1.30 d (3H, 2-CH ,
2-Methylperhydro-1,3-oxazine (Xa). Yield 67%,
20 20
3
3
3
3
J = 4.6 Hz), 2.89 s (1H, NH), 3.50 m (2H, 5-H),
4
H 11.21; N 12.08. C H NO. Calculated, %: C 62.57;
bp 37–38°C (20 mm), d4 = 0.9674, nD = 1.4460;
3
20
.66 q (1H, 2-H, J = 4.6 Hz). Found, %: C 62.30;
published data [9]: bp 68–70°C (100 mm), d = 0.948,
4
20
–1
6
13
n = 1.4382. IR spectrum, ν, cm : 540, 600, 750, 805,
D
H 11.38; N 12.16.
N-Ethylidene-2-vinyloxypropan-1-amine (IIIa).
925, 975, 1065, 1080, 1145, 1170, 1240, 1290, 1390,
1
1
430, 1445, 1460, 2840, 2935, 2975, 3280. H NMR
3
2
0
20
spectrum, δ, ppm: 1.23 d (3H, CH , J = 5.2 Hz),
Yield 31%, bp 83–86°C (80 mm), d = 0.8625, n =
3
4
D
2
0
1
.64 m (2H, 5-H), 2.89 m (2H, 4-H), 3.61 br.s (1H,
1
0
(
.4371; published data [8]: bp 77–78°C (60 mm), d =
.8627, n = 1.4378. IR spectrum, ν, cm : 1600, 1615
C=C), 1660 (C=N), 3105 (=C–H). H NMR spectrum,
4
3
2
0
–1
NH), 3.90 m (2H, 6-H), 4,22 q (1H, 2-H, J = 5.2 Hz).
Found, %: C 58.99; H 10.65; N 13.71. C H NO. Cal-
D
1
5
11
δ, ppm: 1.24 m (3H, OCHCH ), 1.97 d (3H,
culated, %: C 59.37; H 10.96; N 13.85.
3
3
N=CHCH , J = 4.5 Hz), 3.48 m (2H, NCH ), 3.92–
3-(2-Methylperhydro-1,3-oxazin-3-yl)propane-
3
2
2
0
4
.27 m (3H, OCH, cis-CH=C, trans-CH=C), 6.30 d.d
nitrile (Xb). Yield 94%, bp 157–159°C (7 mm), d =
4
3
3
20
D
–1
(
1H, OCH=C, J = 6.8, J
= 14.1 Hz), 7.73 q (1H,
1.0420, n = 1.4709. IR spectrum, ν, cm : 615, 645,
cis
trans
3
N=CH, J = 4.5 Hz). Found, %: C 66.02; H 10.44;
700, 860, 905, 920, 1045, 1105, 1120, 1175, 1230,
1295, 1330, 1395, 1445, 1460, 2240, 2860, 2945, 2975.
N 11.17. C H NO. Calculated, %: C 66.11; H 10.30;
7
13
1
3
N 11.01.
H NMR spectrum, δ, ppm: 1.31 d (3H, CH , J =
3
5
4
5
.4 Hz), 1.67–2.45 m (4H, 5-H, CH CN), 2.89 m (4H,
N-Ethylidene-2-methyl-1-vinyloxypropan-2-
2
3
2
4
0
-H, 4-CH ), 3.91 m (2H, 6-H), 4,12 q (1H, 2-H, J =
amine (IIIb). Yield 3%, bp 60–63°C (45 mm), d
=
2
20
.4 Hz). Found, %: C 62.79; H 9.32; N 18.01.
0
(
.8632, n = 1.4411; published data [8]: bp 64–68°C
D
2
0
20
C H N O. Calculated, %: C 62.31; H 9.15; N 18.17.
48 mm), d = 0.8639, n = 1.4418. IR spectrum, ν,
8
14
2
4
D
–
1
cm : 1605, 1620 (C=C), 1655 (C=N), 3050, 3110
3-Benzyl-2-methylperhydro-1,3-oxazine (Xc).
1
20 20
(
=C–H). H NMR spectrum, δ, ppm: 1.17 s (6H, CH ),
Yield 82%, bp 106–109°C (2 mm), d = 1.0259, n =
4 D
3
3
–1
1
3
4
6
7
.96 d (3H, CHCH , J = 4.2 Hz), 3.55 s (2H, CH O),
.92 d.d (1H, cis-HC=C, J = 2.1, J = 6.7 Hz),
.14 d.d (1H, trans-CH=C, J = 2.1, J = 14.0 Hz),
.44 d.d (1H, OCH=C, J = 6.7, J
1.5190. IR spectrum, ν, cm : 680, 710, 780, 800, 860,
905, 950, 1050, 1070, 1105, 1140, 1175, 1200, 1230,
1250, 1270, 1320, 1380, 1390, 1420, 1445, 1490, 2830,
2920, 2975, 3015, 3050, 3070. H NMR spectrum, δ,
ppm: 1.29 d (3H, CH , J = 5.3 Hz), 1.68 m (2H, 5-H)
3
2
2
3
2
3
3
3
1
= 14.0 Hz),
cis
trans
3
3
.73 q (1H, N=CH, J = 4.2 Hz). Found, %: C 67.92;
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 7 2007

CYCLIZATION OF VINYL ETHERS DERIVED FROM AMINO ALCOHOLS
969
2
.85 m (4H, 4-H, PhCH ), 3.93 m (2H, 6-H), 4.29 q
3. Kukharev, B.F., Stankevich, V.K., Terent’eva, V.P., and
2
3
Kukhareva, V.A., Zh. Org. Khim., 1984, vol. 20, p. 1344.
(
1H, 2-H, J = 5.3 Hz), 6.98–7.45 m (5H, Ph). Found,
%
: C 75.23; H 8.58; N 7.40. C H NO. Calculated, %:
4. Kukharev, B.F., Stankevich, V.K., Klimenko, G.R.,
Terent’eva, V.P., and Kukhareva, V.A., Khim. Geterotsikl.
Soedin., 1986, p. 536.
1
2
17
C 75.35; H 8.96; N 7.32.
5
6
. Valter, R.E., Usp. Khim., 1982, vol. 51, p. 1374.
. Skvortsova, G.G., Shostakovskii, M.F., Samoilova, M.Ya.,
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