The reaction of acetylenic amines with tetraethylammonium carbonate and hydrogen carbonate; synthesis of 5-methylene-1,3-oxazolidin-2-ones

Article abstract of DOI:10.1055/s-2004-836036

The reaction of acetylenic amines 1 with electrochemically generated tetraethylammonium carbonate (TEAC) or chemically generated tetraethylammonium hydrogen carbonate (TEAHC) is reported. Unsubstituted or substituted 5-methylene-1,3-oxazolidin-2-ones 2 ar

Full text of DOI:10.1055/s-2004-836036

LETTER
67
The Reaction of Acetylenic Amines with Tetraethylammonium Carbonate and
Hydrogen Carbonate; Synthesis of 5-Methylene-1,3-oxazolidin-2-ones
S
ynthesis of 5-Me
n
thylene-1,3-o
t
xazolid
o
in-2-ones nio Arcadi, Achille Inesi, Fabio Marinelli, Leucio Rossi,* Mirella Verdecchia
Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università degli Studi, Monteluco di Roio, 67040 L’Aquila, Italy
Fax +39(0862)434203; E-mail: rossil@ing.univaq.it
Received 15 September 2004
In all cases reported, acetylenic amines substituted at the
Abstract: The reaction of acetylenic amines 1 with electrochemi-
terminal position of the triple bond do not react at all or
give a cyclic carbamate only with poor reaction yields
(18% in the only case reported). Also the reaction of
cally generated tetraethylammonium carbonate (TEAC) or chemi-
cally generated tetraethylammonium hydrogen carbonate (TEAHC)
is reported. Unsubstituted or substituted 5-methylene-1,3-oxazol-
idin-2-ones 2 are obtained in moderate to very high yields according amines with 4,4-dimethyl-5-methylene-1,3-dioxolan-2-
one in the presence of palladium catalyst was reported.6
to the reaction conditions adopted and to the nature of the substrate.
Key words: alkynes, amines, cyclizations, carboxylations, oxazol-
idin-2-ones
Here we report the reaction, under mild conditions, of
acetylenic amines 1 with TEAC or TEAHC in aprotic sol-
vents to yield 5-methylene-1,3-oxazolidin-2-ones 2 in
moderate to high yields. Differently from the methods re-
We have recently shown that tetraethylammonium car-
bonate [(Et4N)2CO3; TEAC] and hydrogen carbonate
[Et4NHCO3; TEAHC] are powerful reagents for the car-
boxylation reaction of several organic substrates. In par-
ticular, linear and cyclic carbonates and carbamates are
obtained by reaction of the above reported carboxylating
reagents with alcohols, amines and alkyl halides.1 TEAC
is easily prepared by electrochemical reduction of carbon
dioxide in acetonitrile–tetraethylammonium perchlorate
(TEAP) system, while TEAHC is obtained by reaction of
carbon dioxide with methanol solutions of tetraethylam-
monium hydroxide (TEAOH). Both reagents thus operate
employing the safe and cheap carbon dioxide as source of
carbon and, in addition, perform the syntheses under very
mild reaction conditions being a valuable alternative to
the toxic and harmful phosgene, isocyanates and carbon
monoxide traditionally used in the preparations of carbon-
ates and carbamates.
ported in literature this new methodology allows the syn-
thesis of cyclic carbamates even if acetylenic amines
substituted at the terminal position of the triple bond are
used as starting materials, in such a way to obtain useful
intermediates for further elaborations of the 1,3-oxazol-
idin-2-one ring (Equation 1).
R2
R1
R2
R3
TEAC
R3
NHR4
R1
or TEAHC
O
N
R4
O
1
2
Equation 1 Reaction of acetylenic amines with TEAC or TEAHC
N-Benzyl-N-(1,1-dimethylprop-2-ynyl)amine (1a; R1 =
H; R2 = R3 = Me; R4 = Bn) was used as model compound
in a series of experiments direct to the optimization of the
reaction conditions for the synthesis of 3-benzyl-4,4-
dimethyl-5-methylene-1,3-oxazolidin-2-one (2a; R1 = H;
R2 = R3 = Me; R4 = Bn).
Cyclic carbamates 1,3-oxazolidin-2-ones are useful sub-
strates in organic synthesis. In their optically active form,
they are frequently used as chiral auxiliaries in a wide
range of asymmetric syntheses such as alkylation, acyla-
tion and Diels–Alder reactions, and aldolic condensa-
tions.2 However, only few papers report the synthesis of
5-methylene-1,3-oxazolidin-2-ones (2). The presence of
an exocyclic double bond in these substrates, allows the
further transformation of the 1,3-oxazolidin-2-one and the
preparation of synthetically useful derivatives. The reac-
tion of carbon dioxide with propargylic amines is the
method of choice. The reactions usually proceed in auto-
clave, and may be catalyzed by copper salts,3 ruthenium or
palladium complexes,4 or strong organic bases.5 Mild
reaction conditions are also possible in some instances.5
As highlighted in Table 1, best reaction conditions in-
volve the reaction of 1a with TEAHC or TEAC in a 1:1.5
molar ratio in DMSO at 80 °C (entries 8 and 9). In the sec-
ond case, reaction times are considerably reduced. In
MeCN, usually adopted as solvent of choice in the prece-
dent works, the reaction proceeds only in low yield even
if long reaction times, high temperature or catalyst are
used (entries 1–6). When MeOH is used as solvent the
only 1a is recovered at the end of the reaction (entry 7).
According to the results obtained with the model com-
pound 1a, the methodology was extended to a large num-
ber of acetylenic amines. Results are summarized in
Table 2.
SYNLETT 2005, No. 1, pp 0067–0070
0
5.
0
1.
2
0
0
5
As pointed out in the preliminary results, reactions with
TEAC are generally faster than the respective reactions
Advanced online publication: 29.11.2004
DOI: 10.1055/s-2004-836036; Art ID: G33704ST
© Georg Thieme Verlag Stuttgart · New York

68
A. Arcadi et al.
LETTER
Table 1 Reaction of Propargylic Amine 1a with TEAHC and TEAC under Different Reaction Conditionsa
Entry
Reagent
TEAHC
TEAHC
TEAHC
TEAHC
TEAHC
TEAHC
TEAHC
TEAHC
TEAC
1a/Reagent ratio Solvent
Temp (°C)
Time (h)
120
24
Yield of 2a (%)b
1
2
3
4
5
6
7
8
9
1:1.05
1:1.20
1:1.50
1:1.20
1:1.20
1:1.50
1:1.50
1:1.50
1:1.50
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeOH
DMSO
DMSO
r.t.
80
80
r.t.
r.t.
80
r.t.
80
80
27
32
36
18c
30d
18d
–
48
24
24
24
48
28
91
92
3
a 0.5 mmol of 1a in 10 mL of solvent were normally employed for each experiment.
b Yields refer to isolated product. Unreacted starting material was also recovered.
c The reaction was carried out in the presence of catalytic amount (10%) of Cu(I)I.
d The reaction was carried out in the presence of catalytic amount (10%) of NaAuCl4·H2O.
carried out using TEAHC as carboxylating reagent. The Making reference to our precedent works,1,8 a plausible
reactions proceed smoothly with both substrates bearing reaction mechanism can be proposed; in this pattern, the
substituted or unsubstituted triple bonds. In addition, reac- formation of a carbamate anion and its following addition
tion yields in the case of substituted 5-methylene-1,3-ox- to the carbon-carbon triple bond may be supposed.
azolidin-2-ones, carried out with TEAC are substantially
In a typical procedure TEAHC7 (0.75 mmol) was added to
higher than the corresponding reactions performed with
a solution of propargylic amine (0.5 mmol) in dry DMSO
TEAHC. Propargyl amine (R1 = R2 = R3 = R4 = H) did
(10 mL). The resulting mixture was stirred for the neces-
not provide, in the standard reaction conditions, the wait-
sary time at 60–80 °C and, after addition of water, extract-
ed cyclic compound. Stereochemistry of the resulting
ed with diethyl ether. The residue obtained by evaporation
double bond was established by 1H NMR one-dimension-
of the organic phase is purified by flash chromatography
al NOE experiments and underlined a clear or total pre-
to yield the desired 5-methylene-1,3-oxazolidin-2-one.
Alternatively if TEAC is used as carboxylating reagent a
simple electrochemical procedure is required for its gen-
dominance of the Z-isomer. As an example, NOE
difference spectra obtained in the case of oxazolidinones
2f and 2h by irradiation at d = 5.38 and 5.31 ppm, respec-
tively (corresponding to the signals of the olefinic pro-
tons), clearly showed a cis relationship between the above
reported hydrogen atoms and the alkyl groups (methyl and
ethyl or dimethyl) bonded to the C-4 carbon atom of the
ring.
eration.8 TEAC is obtained by divided cells potential con-
trolled reduction of carbon dioxide (E = –2.1 V vs SCE)
on a copper cathode in a tetraethylammonium perchlorate
(TEAP) 0.1 M DMSO solution. The solution obtained af-
ter the passage of the opportune amount of electricity
(0.75 mmol of TEAC) was used as obtained for the reac-
tion with the propargylic amine (0.5 mmol).
Table 2 Synthesis of 5-Methylene-1,3-oxazolidin-2-ones Starting from Acetylenic Amines and TEAC or TEAHCa
Entry Substrate
Reagent
Temp (°C) Time (h) Product
Yield (%)b
N
H
O
1
TEAC
80
3
92
N
O
1a
2a
2
3
1a
TEAHC
TEAC
80
80
28
2a
91
78
O
2.5
N
H
N
O
1b
2b
Synlett 2005, No. 1, 67–70 © Thieme Stuttgart · New York

LETTER
Synthesis of 5-Methylene-1,3-oxazolidin-2-ones
69
Table 2 Synthesis of 5-Methylene-1,3-oxazolidin-2-ones Starting from Acetylenic Amines and TEAC or TEAHCa (continued)
Entry Substrate
Reagent
TEAHC
Temp (°C) Time (h) Product
Yield (%)b
4
5
6
7
1b
80
48
2b
84
N
H
TEAC
80
2
97
O
N
1c
1c
O
2c
2c
TEAHC
TEAC
60
80
24
3
70
63
H
N
OMe
OMe
O
OMe
OMe
N
O
1d
2d
1e
H
N
Ts
8
9
TEAHC
TEAC
60
80
24
95
1e
O
O
1.5
85c
O
N
HN
1f
O
2f
2f
10
11
1f
TEAHC
TEAHC
60
60
24
24
43
48
O
O
HN
O
N
1g
1h
O
2g
MeO
OMe
NH
12
TEAC
80
22
91d
O
N
O
2h
O
NH
N
O
O
13
TEAHC
80
22
45
O
1i
O
O
2i
a Typical reaction is carried out with amine (0.5 mmol) TEAC or TEAHC (0.75 mmol) in DMSO (10 mL).
b Yields refer to isolated products.
c Z/E Ratio 75:25.
d 100% of Z-isomer.
Synlett 2005, No. 1, 67–70 © Thieme Stuttgart · New York

70
A. Arcadi et al.
LETTER
H), 6.65–6.85 (m, 5 H) ppm. 13C NMR (50.3 MHz, CDCl3):
d = 29.4, 35.9, 45.2, 49.6, 55.8, 55.9, 69.7, 88.8, 111.2,
111.8, 120.6, 132.2, 147.4, 148.8 ppm. Anal. Calcd: C,
72.84; H, 8.56. Found: C, 72.79; H, 8.54.
Unsubstituted propargylamines 1a–e, were obtained by
copper(I) chloride-catalyzed reaction of 1,1-dialkylprop-
2-ynyl acetates with amines.9 Substituted propargyl-
amines 1f–i were synthesized by palladium-catalyzed
coupling of the corresponding unsubstituted amines with
aryl iodides.10
(10) (a) Austin, W. B.; Bilow, N.; Kelleghan, W. J.; Lau, K. S. Y.
J. Org. Chem. 1981, 46, 2280. (b) Synthesis of 1-{4-[3-
(benzylamino)-3-methylpent-1-ynyl]phenyl}ethanone
(1f): To a solution of 1c (1 g, 5.34 mmol) in DMF (2 mL),
and Et3N (4 mL) were added 1-(4-iodophenyl)ethanone
(1.315 g, 5.34 mmol), palladium diacetate (0.024 g, 0.107
mmol) and PPh3 (0.056 g, 0.213 mmol). The mixture was
stirred under N2 at 50 °C for 16 h, then 0.5 M NH4Cl (100
mL) was added and the mixture extracted with Et2O (3 × 50
mL). The combined organic phase was dried (Na2SO4) and
evaporated under reduced pressure. Silica gel
Spectroscopic data for the identification of some 5-meth-
ylene-1,3-oxazolidin-2-one are given.11
In conclusion, both TEAC and TEAHC are reagents able
to promote carboxylation and following cyclization of
propargylic amines to 5-methylene-1,3-oxazolidin-2-
ones. TEAHC affords high reaction yields only with
amines unsubstituted at the triple bonds. Moderate to
good reaction yields are obtained in other cases. Moreover
reaction rates in TEAHC are considerably slower than the
reaction carried out with TEAC, which, in addition, shows
high reaction yields with both unsubstituted and substitut-
ed amines. This last result in particular constitutes an un-
deniable advantage of this method with respect to the
methods reported up to now.
chromatography (hexanes–EtOAc 90:10) afforded 1f (1.265
g, 78% yield). 1H NMR (200 MHz, CDCl3): d = 1.08 (t, 3 H),
1.45 (s, 3 H), 1.48 (br s, 1 H), 1.74 (dq, 2 H), 2.59 (s, 3 H),
3.94 (s, 2 H), 7.20–7.45 (m, 5 H), 7.70 (AA¢XX¢, 4 H) ppm.
13C NMR (50.3 MHz, CDCl3): d = 8.9, 26.3, 26.6, 34.6, 48.7,
54.7, 82.9, 97.5, 127.0, 128.2, 128.4, 128.5, 131.8, 135.9,
140.7, 197.4 ppm. Anal. Calcd: C, 82.58; H, 7.59. Found: C,
82.55; H, 7.56.
(11) Some representative examples are reported:
4,4-Dimethyl-5-methylene-3-(3-phenylpropyl)-1,3-
oxazolidin-2-one (2b): 1H NMR (200 MHz, CDCl3): d =
1.29 (s, 3 H), 1.80–2.00 (m, 2 H), 2.58 (t, 3 H), 3.11 (t, 3 H),
Acknowledgment
4.13 (dd, 1 H), 4.55 (dd, 1 H), 7.10–7.30 (m, 5 H) ppm. 13
C
This work was supported by research grants from M.I.U.R and
C.N.R., Italy.
NMR (50.3 MHz, CDCl3): d = 27.5, 29.6, 30.9, 33.1, 40.0,
61.3, 83.9, 126.0, 128.2, 128.4, 141.0, 154.3, 160.6 ppm.
Anal. Calcd: C, 73.44; H, 7.81. Found: C, 73.49; H, 7.73.
3-Benzyl-4-ethyl-4-methyl-5-methylene-1,3-oxazolidin-
2-one (2c): 1H NMR (200 MHz, CDCl3): d = 0.65 (t, 3 H),
1.17 (s, 3 H), 1.30–1.55 (m, 1 H) 1.60–1.80 (m, 1 H), 4.09
(d, 1 H), 4.32 (AB, 2 H), 4.65 (d, 1 H), 7.15–7.35 (m, 5 H)
ppm. 13C NMR (50.3 MHz, CDCl3): d = 7.6, 27.3, 32.2, 44.0,
65.4, 84.5, 127.8, 128.1, 128.6, 137.4, 155.4, 158.8 ppm.
Anal. Calcd: C, 72.70; H, 7.41. Found: C, 72.63; H, 7.29.
3-[2-(3,4-Dimethoxyphenyl)ethyl]-4,4-dimethyl-5-
methylene-1,3-oxazolidin-2-one (2d): 1H NMR (200 MHz,
CDCl3): d = 1.22 (s, 6 H), 2.75–2.95 (m, 2 H), 3.15–3.35 (m,
2 H), 3.78 (s, 3 H), 3.80 (s, 3 H), 4.12 (d, 1 H), 4.55 (d, 1 H),
6.60–6.80 (m, 3 H) ppm. 13C NMR (50.3 MHz, CDCl3): d =
27.2, 34.5, 42.3, 55.8, 61.2, 84.0, 111.2, 112.0, 120.7, 130.9,
147.6, 148.8, 154.1, 160.5 ppm. Anal. Calcd: C, 65.96; H,
7.27. Found: C, 65.88; H, 7.14.
(5Z)-3-Benzyl-5-(4-methoxybenzylidene)-4,4-dimethyl-
1,3-oxazolidin-2-one (2h): 1H NMR (200 MHz, CDCl3):
d = 1.27 (s, 6 H), 3.71 (s, 3 H), 4.41 (s, 2 H), 5.31 (s, 1 H),
6.70–6.85 (m, 2 H), 7.10–7.30 (m, 5 H), 7.40–7.55 (m, 2 H)
ppm. 13C NMR (50.3 MHz, CDCl3): d = 27.7, 44.0, 55.2,
62.3, 100.1, 113.8, 126.2, 127.7, 128.6, 129.5, 137.5, 151.6,
154.9, 158.3 ppm. Anal. Calcd: C, 74.28; H, 6.55. Found: C,
74.11; H, 6.38.
References
(1) (a) Feroci, M.; Inesi, A.; Rossi, L. In Novel Trends in
Electroorganic Synthesis; Torii, S., Ed.; Springer-Verlag:
Tokio, 1998, and references cited therein. (b) Inesi, A.;
Mucciante, V.; Rossi, L. J. Org. Chem. 1998, 63, 1337.
(c) Feroci, M.; Inesi, A.; Mucciante, V.; Rossi, L.
Tetrahedron Lett. 1999, 40, 6059. (d) Mucciante, V.; Rossi,
L.; Feroci, M.; Sotgiu, G. Synth. Commun. 2002, 32, 1205.
(2) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
835; and references cited therein.
(3) Dimroth, P.; Pasedach, H. (BASF) DE Pat 1164411, 1964;
Chem. Abstr. 1964, 60, 14510.
(4) (a) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y.
Tetrahedron Lett. 1987, 28, 4417. (b) Shi, M.; Shen, Y.-M.
J. Org. Chem. 2002, 67, 16.
(5) (a) Costa, M.; Chiusoli, G. P.; Rizzardi, M. Chem. Commun.
1996, 1699. (b) Costa, M.; Chiusoli, G. P.; Taffurelli, D.;
Dalmonego, G. J. Chem. Soc., Perkin Trans. 1 1998, 1541.
(6) Shi, M.; Shen, Y.-M.; Chen, Y.-J. Heterocycles 2002, 57,
245.
(7) TEAHC is simply obtained by saturating a methanol
solution of tetraethylammonium hydroxide with CO2, see:
Venturello, C.; D’Aloisio, R. Synthesis 1985, 33.
(8) For further details concerning electrogeneration of TEAC,
see: (a) Casadei, M. A.; Inesi, A.; Micheletti Moracci, F.;
Rossi, L. Chem. Commun. 1996, 2575. (b) Casadei, M. A.;
Inesi, A.; Rossi, L. Tetrahedron Lett. 1997, 38, 3565.
(9) (a) Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S.-I. J.
Org. Chem. 1994, 59, 2282. (b) N-[2-(3,4-Dimethoxy-
phenyl)ethyl]-2-methylbut-3-yn-2-amine (1d): 1H NMR
(200 MHz, CDCl3): d = 1.36 (s, 6 H), 1.56 (br s, 1 H), 2.26
(s, 1 H), 2.78 (t, 2 H), 2.98 (t, 2 H), 3.87 (s, 3 H), 3.88 (s, 3
Methyl 3-[(3-Benzyl-4-ethyl-4-methyl-2-oxo-1,3-
oxazolidin-5-ylidene)methyl]benzoate (2i): 1H NMR (200
MHz, CDCl3): d = 0.66 (t, 3 H), 1.18 (s, 3 H), 1.40–1.65 (m,
1 H), 1.70–1.95 (m, 1 H), 3.84 (s, 3 H), 4.38 (AB, 2 H), 5.37
(s, 1 H), 7.15–7.40 (m, 6 H), 7.75–8.10 (m, 3 H) ppm. 13
C
NMR (50.3 MHz, CDCl3): d = 7.7, 27.3, 29.7, 44.1, 52.2,
66.3, 100.1, 127.8, 127.9, 128.1, 128.7, 129.4, 130.3, 132.5,
133.9, 137.2, 152.7, 155.1, 166.8 ppm. Anal. Calcd: C,
72.31; H, 6.34. Found: C, 72.39; H, 6.42.
Synlett 2005, No. 1, 67–70 © Thieme Stuttgart · New York