Synthesis of 2-(1-alkoxyvinyl)oxazolidines by condensation of 2-alkoxypropenals with 2-aminoalkanols and ring-chain tautomerism of the products

Article abstract of DOI:10.1023/B:RUJO.0000010565.77155.ab

Reactions of 2-alkoxypropenals with 2-aminoalkanols afforded tautomeric mixtures of previously unknown 2-(1-alkoxyvinyl)oxazolidines and imino alcohols. The condensation takes 2 h at room temperature (89-100%) or 1-5 min under microwave irradiation. The t

Full text of DOI:10.1023/B:RUJO.0000010565.77155.ab

Russian Journal of Organic Chemistry, Vol. 39, No. 10, 2003, pp. 1477 1483. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 10, 2003,
pp. 1546 1552.
Original Russian Text Copyright
2003 by Keiko, Funtikova, Stepanova, Chuvashev, Larina.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on the 65th Anniversary of His Birth
Synthesis of 2-(1-Alkoxyvinyl)oxazolidines by Condensation
of 2-Alkoxypropenals with 2-Aminoalkanols and Ring Chain
Tautomerism of the Products
N. A. Keiko, E. A. Funtikova, L. G. Stepanova, Yu. A. Chuvashev, and L. I. Larina
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
fax: (3952)419346; e-mail: keiko@irioch.irk.ru
Received June 27, 2003
Abstract Reactions of 2-alkoxypropenals with 2-aminoalkanols afforded tautomeric mixtures of previously
unknown 2-(1-alkoxyvinyl)oxazolidines and imino alcohols. The condensation takes 2 h at room temperature
(89 100%) or 1 5 min under microwave irradiation. The tautomeric equilibrium shifts toward the open-chain
structure with increase in the solvent polarity (CDCl3, CD2OD, DMSO-d6, D2O) and temperature. The
presence of substituents in the oxazolidine ring raises the stability of the cyclic tautomer.
2-Vinyl- and especially 2-vinyl-N-alkyloxazolidines
are widely used in organic synthesis [1], specifically
for the preparation of functionalized cis-3,4-disubsti-
tuted -lactams [2], -amino- -hydroxy acids [3], and
cyclopropylcarbaldehydes [4]. These compounds are
readily involved in such processes as ene reaction [5],
dihydroxylation [6], and epoxidation [5, 7 9]. The
resulting epoxyoxazolidines turned out to be valuable
synthons in the preparation of pheromones and inter-
mediate product in the synthesis of taxol [8, 9].
2-Alkenyloxazolidines are usually prepared by con-
densation of -aminoalkanols with , -unsaturated
aldehydes [4, 8, 10] or the corresponding acetals
[6, 11]. However, no examples have so far been
reported on reactions of -alkoxyacroleins with
-amino alcohols. Such reactions could give rise to
2-(1-alkoxyvinyl)oxazolidines. Unlike the vinyl group
in 2-ethenyloxazolidines, alkoxyvinyl group can be
subjected to hydrolysis with a view to obtain 2-acetyl-
oxazolidines which attract interest as intermediate
products in the synthesis of O-substituted -hydroxy
aldehydes [12].
The goal of our present study was to find optimal
conditions for the reaction of 2-alkoxypropenals with
various 2-aminoalkanols and examine the state of
tautomeric equilibrium between the cyclic oxazolidine
and open-chain imino forms of the products with
regard to the solvent polarity and substituent nature
Scheme 1.
I, R1 = Et (a), Me (b); II, R2 = R3 = R4 = R5 = H (a); R2 = Et, R3 = R4 = R5 = H (b); R2 = R5 = Me, R3 = R4 = H (c); R2 =
R3 = R5 = H, R4 = Me (d); R2 = R5 = H, R3 = R4 = Me (e); III, IV, R1 = Et, R2 = R3 = R4 = R5 = H (a); R1 = Me, R2 = R3 =
R4 = R5 = H (b); R1 = R2 = Et, R3 = R4 = R5 = H (c); R1 = Me, R2 = Et, R3 = R4 = R5 = H (d); R1 = Et, R2 = R5 = Me, R3 =
R4 = H (e); R1 = Me, R2 = R5 = Me, R3 = R4 = H (f); R1 = Et, R2 = R3 = R5 = H, R4 = Me (g); R1 = Me; R1 = Me, R2 = R3 =
R5 = H, R4 = Me (h); R1 = Et, R2 = R5 = H, R3 = R4 = Me (i); R1 = Me, R2 = R5 = H, R3 = R4 = Me (j).
1070-4280/03/3910-1477$25.00 2003 MAIK Nauka/Interperiodica

1478
KEIKO et al.
Reactions of 2-alkoxypropenals Ia and Ib with 2-aminoalkanols IIa IIfa
Solvent ( )
Product ratio, mol %
Run
no.
R1 (I)
R2, R3, R4, R5 (II)
reaction
NMR
III
IV
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Et
Et
Et
Et
Me
Me
Me
Me
Me
Et
Et
Me
Et
Et
Et
Me
Et
Me
Et
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = R3 = R4 = R5 = H
R2 = Et, R3 = R4 = R5 = H
R2 = Et, R3 = R4 = R5 = H
R2 = Et, R3 = R4 = R5 = H
R2 = R5 = Me, R3 = R4 = H
R2 = R5 = Me, R3 = R4 = H
R2 = R5 = Me, R3 = R4 = H
R2 = R5 = Me, R3 = R4 = H
R2 = R3 = R5 = H, R4 = Me
R2 = R3 = R5 = H, R4 = Me
R2 = R5 = H, R3 = R4 = Me
R2 = R5 = H, R3 = R4 = Me
CDCl3 (4.81)b
CD3OD (32.7)
DMSO-d6 (46.45)
D2O (78.3)
CDCl3 (4.81)c
CDCl3 (4.81)b
CD3OD (32.7)
DMSO-d6 (46.45)
D2O (78.3)
CHCl3
CH3OH
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CDCl3
CD3OD
DMSO-d6
D2O
CDCl3
CDCl3
CD3OD
DMSO-d6
D2O
CDCl3
CDCl3
CDCl3
CDCl3
CD3OD
DMSO-d6
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
83
96.2
16
100
100
92.3
75
100
100
100
49
52
55
7
50
7.4
25
15/35d
19/28d
17/28d
91
50
30
70
14
86
96
95
CHCl3
CHCl3
60/39d
76/15d
Me
a
b
c
The reactions were carried out at 22 C (reaction time 1 h).
In dry solvent.
Without binding of H2O.
d
Ratio of diastereoisomers.
(Scheme 1). The reaction was monitored by GC MS
attains 89 100%. The reaction occurs in such a way
in various solvents, including water (see table, run
nos. 4, 9). The process is considerably accelerated by
microwave irradiation. In this case, the condensation
of aldehyde Ia with 2-aminoethanol (IIa) in CH2Cl2
is complete in 1 5 min.
1
and H and 13C NMR; the imino group was readily
1
distinguished by the presence of an H signal at
7.7 ppm, while oxazolidine ring was detected by
a singlet from the 2-H proton which appeared at about
4.7 ppm. The experimental error in the measurement
of signal intensities was reduced by the use of ap-
proximately equal concentrations.
It is essential that the condensation products give
rise to a dynamic ring chain tautomeric equilibrium
III IV. Only a few quantitative data are available
from the literature on the dynamics of tautomeric
transformations of oxazolidines [14, 16 20]. In most
early studies, a little attention was given to analysis
of the product structure, effects of solvent and tem-
perature on the tautomeric equilibrium, and time
necessary for the equilibrium to establish [13, 21].
We have found that the tautomerization process is fast
(on the NMR time scale): presumably, the equilibrium
establishes in a few seconds (cf. [14]). On the other
hand, there are published data [18], according to
which equilibration of the oxazolidine and imino
alcohol tautomers requires 3.7 h.
Insofar as the condensation is a reversible process,
numerous methods for binding of the liberated water
or its removal from the reaction mixture were pro-
posed in order to increase the yield of oxazolidines
(or imino alcohols) [13]. Usually, azeotropic distilla-
tion [10, 14] is used or drying agents (such as MgSO4
[15] or molecular sieves [16, 17]) are added. While
optimizing the conditions for formation of condensa-
tion products III/IV we have found that 2-alkoxy-
propenals readily react (always with heat evolution)
with 2-aminoalkanols at room temperature and that
1
the reaction is complete in 1 h. According to the H
NMR data, the overall yield of tautomers III and IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

SYNTHESIS OF 2-(1-ALKOXYVINYL)OXAZOLIDINES
1479
The ratio of the open-chain and cyclic tautomers
considerably changes, depending on the solvent
polarity: the fraction of the former increases in going
to more polar solvents. Stabilization of the open-chain
form by polar solvents is explained by formation of
a strong hydrogen bond invoving the hydroxy group
[14, 18, 19]. The reaction of 2-ethoxypropenal (Ia)
with 2-aminoethanol (IIa) without a solvent or in
chloroform, methylene chloride, benzene, or methanol,
in the absence and in the presence of 4 molecular
sieves generally afforded a mixture of tautomers IIIa
and IVa at a ratio of 5:1 to 3:1, depending on the
from 3-ethyl-2-hexenal and 2-amino-3-methyl-1-
butanol clearly showed a tendency for the tautomeric
equilibrium to shift toward the imino alcohol structure
on raising the temperature [22]. We examined the
temperature dependence of the tautomeric equilibrium
1
with oxazolidine IVe by H NMR spectroscopy. For
this purpose. a mixture of isomers IIIe and IVe in
CDCl3 (ratio 1:17) was placed in an NMR ampule
and heated for 10 min at 60 C. As a result, the frac-
tion of acyclic tautomer IIIe considerably increased,
and the ratio changed to 1:10. After cooling to 26 C,
the initial tautomer ratio was restored. In another
experiment, the same product was dissolved in
DMSO-d6, and the solution was heated from 28 to
80 C (two spectra were recorded at 1-min intervals)
and cooled first to 50 C and then to 28 C. The ratio
of tautomers IIIe and IVe remained unchanged
(within experimental error) at all the above tempera-
tures (7:3). These data suggest that heating for a short
time does not induce displacement of the equilibrium.
1
conditions. As a rule, before recording the H NMR
spectrum, the liberated water was bound with MgSO4,
the solution was evaporated, and the residue was
dissolved in CDCl3. In order to elucidate the effect
of the solvent polarity on the product ratio, the reac-
tion was carried out in different solvents (see table).
In anhydrous CDCl3, the ratio IIIa:IVa was 5:1,
whereas in methanol-d4, DMSO-d6, and D2O only
acyclic isomer IIIa was detected (run nos. 2 4). The
reaction mixture obtained from 2-methoxypropenal
(Ib) and 2-aminoethanol (IIa) in the presence of
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
4
molecular sieves (run no. 6) contained tautomers
a Bruker DPX-400 spectrometer at 400 (1H) and
100.61 MHz (13C); CDCl3, DMSO-d6, CD3OD, and
CO(CD3)2 were used as solvents, and HMDS, as
internal reference. The IR spectra were measured on
a Specord 75IR spectrometer. Gas chromatographic
mass spectrometric analysis was performed using
an HP 5971A mass-selective detector (electron impact,
70 eV) coupled with an HP 5890 gas chromatograph
(Ultra-2 column, 5% of phenylmethylsilicone; injector
temperature 250 C; oven temperature 70 to 280 C at
a rate of 20 deg/min).
IIIb and IVb at a ratio of 3:1 (in CDCl3). In the
absence of dehydrating agent, this ratio was 12.5:1
(run no. 5). We can conclude that even very small
amount of water in the solvent strongly affects the
state of tautomeric equilibrium. In methanol-d4,
DMSO-d6, and D2O only acyclic isomer IIIb was
formed (run nos. 7 9).
Alkyl substitution leads to considerable increase
in the fraction of ring tautomers IVc IVf (run
nos. 10 13, 16). However, even alkyl-substituted
oxazolidine IVe is converted to an appreciable extent
into the corresponding imino alcohol IIIe in going
from CDCl3 to more polar solvents (run nos. 13 15).
The tautomer ratio IIIe:IVe changes from 1:13 in
CDCl3 to 1:1 in CD3OD and 7:3 in DMSO-d6).
Condensation of 2-alkoxypropenals Ia and Ib
with 2-aminoalkanols IIa IIe (general procedure).
Amino alcohol IIa IIf, 25.2 mmol, was added to
a solution of 25.2 mmol of 2-alkoxypropenal Ia or Ib
in 5 ml of appropriate solvent. The mixture was left
to stand for 1 h at 22 C, dried over MgSO4, filtered
from the drying agent, and evaporated under reduced
pressure. The products were isolated by vacuum dis-
1
According to the H NMR data, the ratio IIIe:IVe
in CD3OD did not change in 15 days. Compounds
IIIc/IVc and IIId/IVd give rise to a three-component
equilibrium, for the cyclic tautomer is a mixture of
two diastereoisomers. No appreciable diastereoselec-
tivity was observed in CDCl3.
1
tillation. The yields were determined by H NMR
spectroscopy before distillation.
The reaction of 2-alkoxypropenals with N-alkyl-
substituted 2-amino alcohols IId and IIe resulted in
formation of 91 to 99% of stable N-substituted oxazo-
lidines IVg IVj which can be stored for a long time
(run nos. 17 20).
It was also interesting to examine the effect of
temperature on the tautomeric equilibrium. As noted
previously [22], the condensation product obtained
Reaction of 2-ethoxypropenal (Ia) with 2-amino-
ethanol (IIa). a. In chloroform. Yield 99.2%. Ratio
IIIa:IVa 5:1. Yield 75% (after distillation), bp 112
113 C (3 mm), n2D2 = 1.4905. Mass spectrum, m/z
(Irel, %): 128 (14) [M Me]+, 114 (6) [M Et]+, 99
(77) [M OEt]+, 84 (85) [M NH(CH2)2O]+, 72 (78)
[CHNH(CH2)2O]+, 68 (72), 56 (100), 45 (47) [OEt]+,
1
41 (45). IR spectrum, , cm : 980, 1070, 1260, 1320,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

1480
KEIKO et al.
1380, 1450, 1600 (C N), 1650 (C C), 2870, 2930,
2980, 3350 (OH). Found, %: C 58.25; H 9.40; N 9.24.
C7H13O2N. Calculated, %: C 58.72; H 9.15; N 9.78.
e. An analogous experiment was carried out in
CH2Cl2 in the presence of 0.14 g of 4 molecular
sieves and 8.3 mg (5 mol %) of p-toluenesulfonic
acid. According to the H NMR spectrum (CDCl3),
the overall yield of tautomers IIIa and IVa (3:1) was
1
2-(1-Ethoxyvinyl)oxazolidine (IVa). 1H NMR
spectrum (CDCl3), , ppm: 1.32 t (3H, CH3, J =
7.2 Hz], 3.03 d.d.d (1H, NCH22, 2J = 11.7, 3J =
100% in 1 min.
3
The reaction of 2-methoxypropenal (Ib) with
2-aminoethanol (IIa) was performed following the
above general procedure.
7.4 Hz), 3.295 d.d.d (1H, NCH2, J = 11.7, J = 6.6,
2
3
3J = 5.0 Hz), 3.72 d.d.d (1H, OCH2, J = 9.4, J
3
2
= 6.6, J = 7.4 Hz), 3.78 d.d.d (1H, OCH2, J = 9.4,
3J = 5.0, J = 7.4 Hz), 4.1 d (1H, CH2 , J = 2.3 Hz),
3
a. In chloroform. Yield 99.45% (before distilla-
tion). The product was a mixture of isomers IIIb and
IVb at a ratio of 1:0.08. After distillation, yield 25%,
bp 90 C (3 mm), n2D2 = 1.4780. Mass spectrum,
4
4.3 d (1H, CH2 , J = 2.3 Hz, J = 1.2 Hz), 4.77 s
(1H, OCHN).
2-Ethoxy-3-(2-hydroxyethylimino)propene
m/z (Irel, %): 129 (5) [M]+, 114 (5) [M
CH3]+,
1
(IIIa). H NMR spectrum (CDCl3), , ppm: 1.4 t (3H,
98 (100) [M OCH3]+, 83 (90), 68 (77), 55 (48),
CH3, J = 7.0 Hz), 3.65 d.t (2H, NCH2, J = 5.5 Hz,
4J = 1.2 Hz), 3.86 t (2H, OCH2, J = 5.5 Hz), 3.90 q
[2H, OCH2 (OEt), J = 7.0 Hz], 4.66 d (1H, CH2 , J =
2.5 Hz), 4.67 d (1H, CH2 , J = 2.5 Hz), 7.73 t (1H,
42 (64), 29 (95).
2-(1-Methoxyvinyl)oxazolidine (IVb). 1H NMR
2
spectrum (CDCl3), , ppm: 3.50 t (1H, NCH2, J =
2
5.2 Hz), 3.67 s (3H, OCH3), 3.81 t (2H, OCH2, J =
4
CH N, J = 1.2 Hz).
5.3 Hz), 4.13 d (1H, CH2 , J = 2.5 Hz), 4.32 d (1H,
CH2 , J = 2.5 Hz), 4.8 s (1H, OCHN).
b. In CD3OD (without binding of water with
MgSO4). Only open-chain isomer IIIa was formed in
3-(2-Hydroxyethylimino)-2-methoxypropene
1
96.2% yield. H NMR spectrum (CD3OD), , ppm:
1
(IIIb). H NMR spectrum (CDCl3), , ppm: 3.61 t
1.36 t (3H, CH3, J = 7.0 Hz), 3.58 t (2H, NCH2, J =
5.2 Hz), 3.78 t (2H, OCH2, J = 5.2 Hz), 3.88 q (2H,
OCH2CH3, J = 7.0 Hz), 4.66 d (1H, CH2 , J =
2.5 Hz), 4.78 d (1H, CH2 , J = 2.5 Hz), 7.73 s
(1H, CH N).
(2H, NCH2, J = 5.2 Hz), 3.66 s (3H, OCH3), 3.81 t
(2H, OCH2, J = 5.2 Hz), 4.56 d (1H, CH=, J =
2.6 Hz), 4.69 d (1H, CH , J = 2.6 Hz), 7.71 s
(1H, CH N).
b. In CD3OD (without removal of water). Yield
of open-chain isomer IIIb 99.45%. 1H NMR spectrum
(CD3OD), , ppm: 3.55 t (2H, NCH2, J = 5.6 Hz),
3.66 s (3H, OCH3), 3.73 t (2H, OCH2, J = 5.6 Hz),
c. In D2O. Only open-chain isomer IIIa was
1
formed in 100% yield. H NMR spectrum (D2O), ,
ppm: 1.25 t (3H, CH3, J = 7.0 Hz), 3.52 t (2H, NCH2,
J = 5.2 Hz), 3.71 t (2H, OCH2, J = 5.2 Hz), 3.83 q
(2H, OCH2CH3, J = 7.0 Hz), 4.66 d (1H, CH2 , J =
2.5 Hz), 4.82 d (1H, CH2 , J = 2.5 Hz), 7.68 s
(1H, CH N).
4.68 d (1H, CH2 , J = 2.5 Hz), 4.81 d (1H, CH2
,
J = 2.5 Hz), 7.74 s (1H, CH N). 13C NMR spectrum
(CD3OD), , ppm: 55.62 (OCH3), 62.33 (NCH2),
63.36 (OCH2), 95.75 ( CH2), 159.25 (OC ),
161.60 (CH N).
d. In DMSO-d6 (both with and without binding of
1
c. In D2O. Only open-chain isomer IIIb was
water). Only open-chain isomer IIIa was formed. H
1
NMR spectrum (DMSO-d6), , ppm: 1.27 t (3H, CH3,
J = 7.0 Hz), 3.58 t (2H, NCH2, J = 5.4 Hz), 3.78 t
(2H, OCH2, J = 5.4 Hz), 3.79 q (2H, OCH2CH3, J =
7.0 Hz), 4.62 d (1H, CH2 , J = 2.5 Hz), 4.63 d (1H,
CH2 , J = 2.5 Hz), 7.66 s (1H, CH N). 13C NMR
spectrum (DMSO-d6), , ppm: 14.30 (CH3), 60.56
(NCH2), 62.94 (CH2OH), 63.12 (OCH2CH3), 93.63
( CH2), 157.42 (OC ), 158.79 (CH N).
formed in 100% yield. H NMR spectrum (D2O), ,
ppm: 3.50 t (2H, NCH2, J = 5.5 Hz), 3.59 s (3H,
OCH3), 3.70 t (2H, OCH2, J = 5.5 Hz), 4.68 d (1H,
CH2 , J = 2.6 Hz), 4.84 d (1H, CH2 , J = 2.6 Hz),
7.70 s (1H, CH N).
d. In DMSO-d6 (without binding of water). Yield
1
of isomer IIIb 100%. H NMR spectrum (DMSO-d6),
, ppm: 1.27 t (3H, CH3, J = 7.0 Hz), 3.49 t (2H,
NCH2, J = 5.5 Hz), 3.57 s (3H, OCH3), 3.58 t (2H,
OCH2, J = 5.5 Hz), 4.65 d (1H, CH2 , J = 2.2 Hz),
4.69 d (1H, CH2 , J = 2.2 Hz), 7.69 s (1H, CH N).
Reaction of 2-ethoxypropenal (Ia) with 2-amino-
butanol (IIb). a. The reaction was carried out in
CDCl3 following the general procedure, but no drying
agent was added. Overall yield of isomers IIIc and
e. 2-Aminoethanol (IIa), 0.059 g (0.97 mmol),
and 4 molecular sieves, 0.1 g, were added to a solu-
tion of 0.097 g (0.97 mmol) of 2-ethoxypropenal (Ia).
The mixture was irradiated for 5 min in a microwave
1
oven at a power of 300 W. According to the H NMR
spectrum (CDCl3), the ratio of tautomers IIIa and
IVa was 5:1; yield 99%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

SYNTHESIS OF 2-(1-ALKOXYVINYL)OXAZOLIDINES
1481
1
IVc 98.5%; ratio IIIc:IVc:IVc 1:0.3:0.7. Yield
63.6% (after distillation), bp 105 C (4 mm), nD22
Stereoisomer IVd . H NMR spectrum (CDCl3), ,
ppm: 0.95 t (3H, CH3, J = 7.46 Hz), 1.59 m (2H,
CH2), 3.04 m (1H, CH), 3.59 s (3H, OCH3), 3.71 m
(2H, OCH2), 4.10 d (1H, CH2 , J = 2.6 Hz), 4.33 d
(1H, CH2 , J = 2.6 Hz), 4.88 s (1H, NCHO).
=
1.4804. Mass spectrum (all isomers gave a single GC
peak), m/z (Irel, %): 171 (1) [M]+, 156 (9) [M CH3]+,
142 (5) [M CH2CH3]+, 127 (22), 112 (100), 100
(86) [M
CH2 COCH2CH3]+, 96 (57), 84 (44),
3-(1-Hydroxymethylpropylimino)-2-metoxypro-
pene (IIId). H NMR spectrum (CDCl3), , ppm:
1
55 (27), 42 (24).
0.82 t (3H, CH3, J = 7.46 Hz), 1.59 m (2H, CH2CH3),
3.69 s (3H, OCH3), 3.71 m (2H, OCH2), 4.57 d (1H,
CH2 , J = 2.6 Hz), 4.70 d (1H, CH2 , J = 2.6 Hz),
7.71 s (1H, CH N). Found (isomer mixture), %:
C 60.55; H 10.00; N 9.13. C8H15O2H. Calculated, %:
C 61.12; H 9.62; N 8.91.
2-(1-Ethoxyvinyl)-4-ethyloxazolidine (IVc) (first
diastereoisomer). H NMR spectrum (CDCl3), , ppm:
1
0.99 t (3H, CH3, Et, J = 7.4 Hz), 1.31 t (3H, CH3,
OEt, J = 7.0 Hz), 1.52 m (2H, CH2, Et), 3.2 m (1H,
CH), 3.79 m (2H, OCH2), 3.92 q (2H, OCH2, Et, J =
7.0 Hz), 4.10 d (1H, CH2 , J = 2.3 Hz), 4.32 d (1H,
CH2 , J = 2.3 Hz), 4.79 s (1H, NCHO).
Reaction of 2-ethoxypropenal (Ia) with 2-amino-
2-methylpropanol (IIc). The reaction was carried out
following the general procedure without a drying
agent. Overall yield 98%, ratio of isomers IIIe and
IVe 0.08:1. After distillation, yield 56%, bp 98 C
(15 mm), n2D2 = 1.4562. Mass spectrum (both isomers
gave a single GC peak), m/z (Irel, %): 156 (5) [M
CH3]+, 140 (11), 126 (5) [M OCH2CH3]+, 112 (26),
100 (100) [M CH2 COCH2CH3]+, 84 (33), 71 (1)
[CH2 COCH2CH3]+, 55 (25), 42 (32). IR spectrum,
2-(1-Ethoxyvinyl)-4-ethyloxazolidine (IVc )
(second diastereoisomer). 1H NMR spectrum (CDCl3),
, ppm: 0.95 (3H, CH3, Et, J = 7.4 Hz), 1.31 t (3H,
CH3, OEt, J = 7.1 Hz), 1.52 m (2H, CH2, Et), 3.20 m
(1H, CH), 3.61 m (2H, OCH2), 3.92 q (2H, OCH2,
Et, J = 7.0 Hz), 4.07 d (1H, CH2 , J = 2.3 Hz),
4.29 d (1H, CH2 , J = 2.3 Hz), 4.84 s (1H, NCHO).
2-Ethoxy-3-(1-hydroxymethylpropylimino)pro-
1
pene (IIIc). H NMR spectrum (CDCl3), , ppm:
1
, cm : 960, 1060, 1105, 1245, 1290, 1380, 1460,
0.83 t (3H, CH3, Et, J = 7.5 Hz), 1.38 t (3H, CH3,
OEt, J = 7.0 Hz), 1.52 m (2H, CH2, Et), 3.34 m (1H,
CH), 3.78 q (2H, OCH2, Et, J = 7.0 Hz), 4.54 d (1H,
CH2 , J = 2.3 Hz), 4.57 d (1H, CH2 , J = 2.3 Hz),
7.69 s (1H, CH N). Found (for isomer mixture), %:
C 63.17; H 10.07; N 8.22. C9H17O2H. Calculated, %:
C 63.13; H 10.01; N 8.18.
1590 (C N), 1640 (C C), 2865, 2970, 3310 br (OH).
2-(1-Ethoxyvinyl)-4,4-dimethyloxazolidine (IVe).
1H NMR spectrum (CDCl3), ppm: 1.19 s (3H, CH3),
1.31 t (3H, CH3CH2, J = 7.0,Hz), 3.34 d (1H, OCH2,
J = 7.2 Hz), 3.58 d (1H, OCH2, J = 7.2 Hz), 3.80 q
(2H, OCH2CH3, J = 7.0 Hz), 4.10 d (1H, CH2
,
J = 2.2 Hz), 4.33 d (1H, CH2 , J 2.2 Hz), 4.89 s
(1H, NCHO).
b. The reaction of aldehyde Ia with amino alcohol
IIb was carried out in methanol without a drying
agent. Evaporation of the solvent afforded 99% of
a mixture of isomers IIIc, IVc, and IVc at a ratio
of 1:0.33:0.50.
2-Ethoxy-3-(2-hydroxy-1,1-dimethylethylimino)-
1
propene (IIIe). H NMR spectrum (CDCl3), , ppm:
1.17 s (3H, CH3), 1.36 t (3H, CH3CH2, J = 7.0 Hz),
3.90 q (2H, OCH2CH3, J = 7.0 Hz], 3.47 s (2H,
OCH2), 4.59 d (1H, CH2 , J = 2.3 Hz), 4.60 d (1H,
CH2 , J = 2.3 Hz), 7.68 s (1H, CH N). Found
(isomer mixture), %: C 63.11; H 10.07; N 8.52.
C9H17O2H. Calculated, %: C 63.13; H 10.01; N 8.18.
A mixture of tautomers IIIe and IVe obtained in
the above experiment was dissolved in CDCl3, and the
solution was placed in an NMR ampule and heated
for 10 min at 60 C. The ratio of tautomers IIIe and
IVe became 1:10. After cooling to 26 C, the initial
tautomer ratio was restored. When the same tautomer
mixture was heated in DMSO-d6 for 1 min at 80 C
and cooled first to 50 C and then to 28 C, the ratio
of IIIe and IVe remained the same at all the above
temperatures (7:3).
Reaction of aldehyde (Ib) with 2-aminobutanol
(IIb). The reaction was carried out following the
general procedure, in CDCl3 without binding of water.
Overall yield 100%; the ratio of products IIId, IVd,
and IVd was 1:0.33:0.50. After distillation, yield
63.2%; bp 104 C (4 mm), n2D2 = 1.4770. Mass spec-
trum (all isomers gave a single GC peak), m/z (Irel, %):
157 (1) [M]+, 142 (3) [M CH3]+, 126 (100) [M
OCH3]+, 112 (17), 100 (63) [M
CH2 COCH3]+,
84 (17), 57 (11) [CH2 COCH3]+, 42 (26).
4-Ethyl-2-(1-methoxyvinyl)oxazolidine (IVd).
1H NMR spectrum (CDCl3), , ppm: 1.00 t (3H, CH3,
J = 7.46 Hz), 1.59 m (2H, CH2), 3.20 m (1H, CH),
3.61 s (3H, OCH3), 3.71 m (2H, OCH2), 4.15 d (1H,
CH2 , J = 2.57 Hz), 4.35 d (1H, CH2 , J = 2.57 Hz),
4.81 s (1H, NCHO).
Reaction of 2-methoxypropenal (Ib) with
2-amino-2-methylpropanol (IIc). Following the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

1482
KEIKO et al.
7.3 Hz, J = 6.7, J = 3.9 Hz], 3.98 d.d.d [2H, OCH2
3
3
general procedure without a drying agent, a mixture
of isomers IIIf and IVf (0.16:1) was formed in
100% yield (after distillation, 61.9%); bp 94 C
(3 mm), n2D2 = 1.4620. Mass spectrum (both isomers
gave a single GC peak), m/z (Irel, %): 157 (7) [M]+,
2
3
3
(ax), J = 7.3, J = 7.7, J = 6.7 Hz], 4.13 d (1H,
CH2 , J = 2.3 Hz), 4.28 d (1H, CH2 , J = 2.3 Hz),
4.21 s (1H, NCHO). 13C NMR spectrum (CDCl3),
,
ppm: 39.31 (CH3), 54.02 (CH2N), 55.30 (OCH3C),
65.31 (OCH2), 84.64 (CH2 ), 96.68 (NCHO), 160.01
(C ). Mass spectrum, m/z (Irel, %): 143 (7) [M]+, 128
(1) [M CH3]+, 112 (1) [M OCH3]+, 98 (19), 86
(100) [M CH2 COCH3]+, 58 (53), 42 (52). IR spec-
142 (4) [M CH3]+, 126 (56) [M OCH3]+, 112 (56),
100 (100) [M
CH2 COCH3]+, 80 (9), 73 (11)
[CH2 COCH2CH3]+, 55 (40), 42 (49).
2-(1-Methoxyvinyl)-4,4-dimethyloxazolidine
(IVf). H NMR spectrum (CD3OD), , ppm: 1.16 s
(3H, CH3), 1.26 s (3H, CH3), 3.36 d (1H, OCH2, J =
7.2 Hz), 3.54 d (1H, OCH2, J = 7.2 Hz), 3.59 s
(2H, OCH3), 4.18 d (1H, CH2 , J = 2.4 Hz), 4.35 d
(1H, CH2 , J = 2.4 Hz), 4.88 s (1H, NCHO).
3-(2-Hydroxy-1,1-dimethylethylimino)-2-meth-
oxypropene (IIIf). H NMR spectrum (CD3OD), ,
ppm: 1.15 s (6H, CH3), 3.66 s (2H, OCH3), 3.42 s
(2H, OCH2), 4.67 d (1H, CH2 , J = 2.5 Hz), 4.78 d
(1H, CH2 , J = 2.5 Hz), 7.74 s (1H, CH N).
1
1
trum, , cm : 1070, 1150, 1195, 1240, 1310, 1330,
1440, 1620, 1660, 1780, 2940. Found, %: C 58.72;
H 9.15; N 9.78. C7H13HO2. Calculated, %: C 58.27;
H 9.03; N 9.93.
2-(1-Ethoxyvinyl)-3,5-dimethyloxazolidine (IVi)
was synthesized from 2-ethoxypropenal (Ia) and
1-methylamino-2-propanol (IIe) following the general
procedure. Yield 99% (after distillation, 52%),
bp 98 C (15 mm), n2D2 = 1.4485, diastereoisomer ratio
IVi:IVi = 3:2. Mass spectrum (both isomers gave
a single GC peak), m/z (Irel, %): 171 (2) [M]+, 156 (1)
1
2-(1-Ethoxyvinyl)-3-methyloxazolidine (IVg) was
synthesized from 2-ethoxypropenal (Ia) and 2-methyl-
aminoethanol (IId) following the general procedure.
Yield 96% (after distillation, 70%), bp 58 C (3 mm),
[M
CH3]+, 142 (1) [M
CH2CH3]+, 100 (100)
[M CH2 COCH2CH3]+, 72 (42), 57 (8), 42 (28).
1
IR spectrum, , cm : 960, 1005, 1070, 1150, 1220,
n2D2 = 1.4560. H NMR spectrum (CDCl3), , ppm:
1
1295, 1360, 1440, 1620, 1660 (C C), 2780, 2960.
1
1.32 t (3H, CH3CH2, J = 7.0 Hz), 2.41 s (3H, CH3),
2.65 d.d.d [2H, NCH2 (ax), J = 9.6, J = 7.2, J =
Isomer IVi. H NMR spectrum (CDCl3), , ppm:
2
3
3
1.27 d (3H, CH3CH, J = 6.1 Hz), 1.33 t (3H,
CH3CH2, J = 7.0 Hz), 2.19 d.d (2H, NCH2, J =
8.9 Hz), 2.37 s (1H, NCH3), 3.35 d.d (1H, CHCH3,
J = 8.9 Hz), 3.79 q (3H, OCH2CH3, J = 7.0 Hz),
4.17 s (1H, NCHO), 4.30 d (1H, CH2 , J = 2.0 Hz),
4.31 d (1H, CH2 , J = 2.0 Hz). 13C NMR spectrum
(CDCl3), C, ppm: 14.21 (CH3CH2), 19.24 (CH3CH),
38.91 (NCH3), 60.25 [OCH2CH3), 62.27 (CH2N),
73.49 (CHCH3), 84.41 (CH2 ), 96.41 (NCHO),
159.71 (C ).
2
3
7.1 Hz], 3.27 d.d.d [2H, NCH2 (eq), J = 9.6, J =
3
6.6, J = 4.3 Hz], 3.79 q (2H, OCH2CH3, J = 7.0 Hz),
2
3
3
3.92 d.d.d [2H, OCH2 (eq), J = 7.1, J = 6.6, J =
4.3 Hz], 3.97 d.d.d [2H, OCH2 (ax), J = 7.1, J =
7.2 Hz, J = 7.1 Hz], 4.06 d (1H, CH2 , J = 2.0 Hz),
2
3
3
4.28 d (1H, CH2 , J = 2.0 Hz), 4.24 s (1H, NCHO).
13C NMR spectrum (CDCl3), C, ppm: 14.21
(CH3CH2), 39.70 (CH3), 54.09 (CH2N), 63.29
(OCH2CH3), 65.22 (OCH2), 84.01 (CH2 ), 96.60
(NCHO), 157.28 (C ). Mass spectrum, m/z (Irel, %):
1
Isomer IV . H NMR spectrum (CDCl3), , ppm:
157 (5) [M]+, 142 (1) [M
CH3]+, 128 (1) [M
1.30 d (3H, CH3CH, J = 6.3 Hz), 1.32 (3H, CH3CH2,
J = 7.0 Hz), 2.40 s (1H, NCH3), 2.75 d.d (1H, NCH2,
J = 9.6 Hz), 2.90 d.d (1H, NCH2, J = 9.6 Hz), 3.8 q
(2H, OCH2CH3, J = 7.0 Hz), 4.06 d (1H, CH2 , J =
1.9 Hz), 4.08 d (1H, CH2 , J = 1.9 Hz), 4.24 d.d (1H,
CHCH3, J = 5.4 Hz), 4.28 s (1H, NCHO). 13C NMR
spectrum (CDCl3), C, ppm: 14.27 (CH3CH2), 20.31
(CH3CH), 39.95 (NCH3), 60.25 (OCH2CH3), 63.21
(CH2N), 72.36 (CHCH3), 84.03 (CH2 ), 97.32
(NCHO), 160.24 (C ). Found, %: C 63.13; H 10.01;
N 8.18. C9H17NO2. Calculated, %: C 63.60; H 9.73;
N 8.55.
CH2CH3]+, 112 (1) [M
OCH2CH3]+, 98 (12), 86
(100) [M
CH2 COCH2CH3]+, 58 (41), 42 (29).
1
IR spectrum, , cm : 970, 1060, 1145, 1240, 1305,
1450, 1625, 1700, 2780, 2970. Found, %: C 61.27;
H 9.55; N 8.86. C8H15NO2. Calculated, %: C 61.12;
H 9.62; N 8.91.
2-(1-Methoxyvinyl)-3-methyloxazolidine (IVh)
was synthesized from 2-methoxypropenal (Ib) and
2-methylaminoethanol (IId) following the general
procedure. Yield 95% (after distillation, 52%), bp 45
46 C (2 mm), n2D2 = 1.4590. 1H NMR spectrum
(CDCl3), , ppm: 2.40 s (3H, CH3H), 2.63 d.d.d [2H,
NCH2 (ax), J = 9.5, J = 7.7, 3J = 6.7 Hz], 3.26 d.d.d
[2H, NCH2 (eq), J = 9.5, J = 6.7, J = 3.9 Hz],
2-(1-Methoxyvinyl)-3,5-dimethyloxazolidine
(IVj) was synthesized from 2-methoxypropenal (Ib)
and 1-methylamino-2-propanol (IIe) following the
general procedure. Yield 91% (after distillation,
2
3
2
3
3
2
3.61 s (3H, OCH3), 3.94 d.d.d [2H, OCH2 (eq), J =
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

SYNTHESIS OF 2-(1-ALKOXYVINYL)OXAZOLIDINES
1483
65.7%), bp 67 C (5 mm), n2D2 = 1.4507; stereoisomer
ratio IVj:IVj = 5:1. Mass spectrum (both isomers
gave a single GC peak), m/z (Irel, %): 157 (5) [M]+,
4. Abdallah, H., Cree, R., and Carrie, R., Tetrahedron
Lett., 1982, vol. 23, p. 503.
5. Adam, W., Peters, K., Peters, E.-M., and Scham-
bony, S.B., J. Am. Chem. Soc., 2001, vol. 123,
p. 7228.
6. Colombo, L., Gennari, C., Poli, G., and Scolas-
tico, C., Tetrahedron Lett., 1985, vol. 26, p. 5459.
7. Adam, W. and Schambony, S.B., Org. Lett., 2001,
142 (1), 128 (1), 100 (100) [M
CH2 COCH3]+,
98 (39), 87 (1) [M CH2 C(OCH3)CH]+, 72 (72),
57 (21) [CH2 COCH3]+, 42 (66). IR spectrum,
,
1
cm : 895, 1005, 1070, 1160, 1220, 1310, 1380,
1445, 1625, 1660, 2780, 2960. Found, %: C 59.12;
H 9.62; N 8.91. C8H15O2H. Calculated, %: C 59.21;
H 9.71; N 8.61.
p. 79.
8. Agami, C., Couty, F., Hamon, L., and Venier, O.,
J. Org. Chem., 1997, vol. 62, p. 2106.
9. Agami, C., Conty, F., Evano, G., and Mathieu, H.,
Tetrahedron, 2000, vol. 56, p. 367.
10. Sadykh-Zade, S.I., Aliev, A.B., Novruzov, S.A., and
1
Isomer IVj. H NMR spectrum (CDCl3), , ppm:
1.27 d (3H, CH3CH, J = 6.0 Hz), 2.18 d.d (1H,
NCH2, J = 9.0 Hz), 2.35 s (1H, NCH3), 3.37 d.d
(1H, CHCH3, J = 8.6 Hz), 3.63 s (3H, OCH3), 4.17 s
(1H, NCHO), 4.33 d (1H, CH2 , J = 2.2 Hz), 4.36 d
(1H, CH2 , J = 2.2 Hz). 13C NMR spectrum (CDCl3),
C, ppm: 19.33 (CH3CH), 38.65 (NCH3), 55.41
(OCH3), 62.33 (CH2N), 73.77 (CHCH3), 85.33
(CH2 ), 96.73 (NCHO), 160.11 (C ).
Melikov, T.M., Azerb. Khim. Zh., 1983, p 71.
11. Bernardi, A., Cardani, S., Pilati, T., Poli, G., Scolas-
tico, C., and Villa, R., J. Org. Chem., 1988, vol. 53,
p. 1600.
12. Colombo, L. and Di Giacomo, M., Tetrahedron Lett.,
1
1999, vol. 40, p. 1977.
Isomer IVj . H NMR spectrum (CDCl3), , ppm:
1.31 d (3H, CH3CH, J = 6.1 Hz), 2.38 s (1H, NCH3),
2.73 d.d (1H, NCH2, J = 9.2 Hz), 2.90 d.d (1H,
NCH2, J = 9.2 Hz), 3.61 s (3H, OCH3), 4.12 d (1H,
CH2 , J = 2.2 Hz), 4.15 d (1H, CH2 , J = 2.2 Hz),
4.25 s (1H, NCHO), 4.33 d.d (1H, CHCH3, J =
13. Kukharev, B.F., Doctoral (Chem.) Dissertation,
Irkutsk, 1997.
14. Fulop, F., Pihlaja, K., Neuvonen, K., Bernath, G.,
Argay, G., and Kalman, A., J. Org. Chem., 1993,
vol. 58, p. 1967.
5.9 Hz). 13C NMR spectrum (CDCl3), C, ppm: 20.59
(CH3CH), 39.81 (NCH3), 55.53 (OCH3), 60.27
(CH2N), 72.48 (CHCH3), 84.62 (CH2 ), 97.52
(NCHO), 161.3 (C ).
This study was financially supported by the Rus-
sian Foundation for Basic Research (project no. 03-
03-33143).
15. Agami, C., Comesse, S., Kadouri-Puchot, C., and
Lusinchi, M., Synlett., 1999, p. 1094; Jwano-
wicz, E.I., Blomgren, P., Cheng, P.T.W., Smith, K.,
Lau, W.F., Pan, Y.Y., Gu, H.H., Malley, M.F., and
Gougoutas, J.Z., Synlett, 1998, p. 664.
16. Adami, C. and Rizk, T., Tetrahedron, 1985, vol. 41,
p. 537.
17. Mangeney, P., Alexakis, A., and Normant, J.E.,
Tetrahedron, 1984, vol. 40, p. 1803.
18. Spassov, S.L., Markova, L., Argirov, O., and Obre-
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