A convenient method for the synthesis of carbamate esters from amines and tetraethylammonium hydrogen carbonate

Full text of DOI:10.1021/jo971695y

J . Org. Chem. 1998, 63, 1337-1338
1337
A Con ven ien t Meth od for th e Syn th esis of
Ca r ba m a te Ester s fr om Am in es a n d
Tetr a eth yla m m on iu m Hyd r ogen Ca r bon a te
wise, phosphocarbamates [P(NR
2
)
3-x(O
2
CNR
2
)
x
, obtained
by insertion of CO in the P-N bonds of aminophos-
2
phines] and alkylammonium carbamates (obtained by
direct interaction of primary and secondary amines with
7
CO
2
) react with alkyl halides mainly to give N-alkylation
Achille Inesi, Vittoria Mucciante, and Leucio Rossi*
6
a,b
products.
These results suggest that the transfer
Dipartimento di Chimica, Ingegneria Chimica e Materiali,
Universit a` degli Studi, I-67040 Monteluco di Roio,
L’Aquila, Italy
reaction of carbamate group from the intermediate ion
pair to an alkylating reagent is strongly affected by the
anion-cation interaction, which can depress the oxygen
nucleophilicity. In fact, the alkylation of the carbamate
anion provides the corresponding carbamates only in low
Received September 11, 1997
8
Organic carbamates represent an important class of
compounds, largely employed in pharmacology (medical
drugs), agriculture (pesticides, fungicides, herbicides),
to moderate yields and under drastic reaction conditions.
On the other hand, the addition of suitable crown ethers
(capable of coordinating the cation) makes O-alkylation
significantly competitive; the role of crown ethers in the
synthesis of carbamic esters has been recently de-
1
and chemical industry (intermediates of synthesis).
Their use as protective groups for the amine function of
amino acids in peptide chemistry is also well-known.2
Several attempts have been made to replace the classical
syntheses, which involve the direct reaction of alcohols
with phosgene or its derivative isocyanates, with new
methodologies employing less toxic and dangerous re-
agents. Important results were obtained by means of
both the homogeneous catalytic carbonylation of ni-
5,9
scribed.
Recently, we investigated the synthesis of linear and
cyclic carbamates by means of electrochemical proce-
dures. In particular, we found that electrochemically
activated carbon dioxide (by either direct reduction or by
reaction with electrochemically generated superoxide ion)
reacts, under mild reaction conditions, with several
aliphatic and aromatic amines, as well as with N-acyl or
N-alkoxycarbonyl alkylamines, affording the correspond-
ing carbamates in high to excellent yields.10 This reac-
tivity is probably to be ascribed to tetraalkylammonium
carbonate and peroxydicarbonate, which are formed as
3
4
troaromatics and the oxidative carbonylation of amines.
More recently carbon dioxide, a cheap and abundant
reagent, has been proposed as a trouble-free starting
material to replace phosgene.5 The direct incorporation
of carbon dioxide into amines, which leads to ionic
carbamates, can be mediated by both metal and nonmetal
species. These compounds behave as bidentate ions and,
in the presence of an alkylating reagent, reactions of
O-alkylation (formation of carbamic esters) and N-
alkylation are both theoretically possible. In the case of
metal-carbamates, electrophilic attack by alkylating
reagents usually affords N-alkylation products.6 Like-
1
1
main products in the direct or in the dioxygen-medi-
ated12 reduction of carbon dioxide, respectively. These
considerations prompted us to investigate the reactivity
of both tetraalkylammonium carbonates and hydrogen
carbonates toward amines in order to develop a new class
of carboxylating reagents.
Herein, we report a simple and safe methodology for
the synthesis of linear and cyclic alkyl and aryl carbam-
ates by reaction of amines with tetraethylammonium
hydrogen carbonate (TEAHC). This compound was first
used by Venturello1 in the synthesis of cyclic carbonates
starting from the corresponding halohydrins.
*
Tel: +39-862-434216. Fax: +39-862-434203. E-mail: rossil@
ing.univaq.it.
(1) (a) Adams, P.; Baron, F. A. Chem. Rev. (Washington, D.C.) 1965,
3a
6
5, 567. (b) Mateen, A.; Chapalamadugu, S., Kashar, B.; Batthi, A. R.;
Chaudry, G. R. Biol. Degrad. Biorem. Toxic. Chem. 1994, 198. (c)
Wigfiled, Y. Y. Food Sci. Technol. (N. Y.) 1996, 77 (Handbook of Food
Analysis, vol. 2) 1501.
TEAHC was simply obtained by saturating a methanol
(
2) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons, Inc.: New York, 1991; pp
15-348.
3) (a) Ragaini, F.; Cenini, S.; Demartin, F. J . Chem. Soc. Chem.
Commun. 1992, 1467. (b) Ragaini, F.; Cenini, S. Chim. Ind. (Milan)
996, 18, 421. (c) Tafesh, A. M.; Weiguny, J . Chem. Rev. (Washington,
D.C.) 1996, 96, 2035. (d) Ragaini, F.; Cenini, S. J . Mol. Catal. A Chem.
solution of commercially available tetraethylammonium
13
hydroxide (TEAOH) with carbon dioxide.
The pale
3
brown highly hygroscopic solid obtained after removal
of the solvent was allowed to react, in acetonitrile at room
temperature, with different amines 1 and alkylating
(
1
1
1
996, 109, 1. (e) J akus, V.; Bojsova, E. Collect, Czech. Chem. Commun.
992, 57, 1505. (f) Leconte, P.; Metz, F.; Mortreux, A.; Osborn, J . A.;
(7) Schroth, W.; Schaedler, H. D.; Andersch, J . Z. Chem. 1989, 29,
129.
Paul, F.; Petit, F.; Pillot, A. J . Chem. Soc. Chem. Commun. 1990, 22,
1
616. (g) Bender, R.; Braunstein, P.; De Bellefon, C. D. M. Polyhedron
988, 7, 2271. (h) Cenini, S.; Pizzotti, M.; Crotti, C.; Ragaini, F.; Porta,
(8) (a) Yoshida, Y.; Ishii, S.; Watanabe, M.; Yamashita, T. Bull.
Chem. Soc. J pn. 1989, 62, 1534. (b) Hori, Y.; Nagano, T.; Nakao, S.;
Fukuhara, T.; Taniguchi, H. Chem. Express 1986, 1, 224. (c) McGhee,
W.; Riley, D. P.; Christ, M. E.; Christ, K. M. Organometallics 1993,
12, 1429.
(9) Aresta, M.; Quaranta, E. Tetrahedron 1992,48, 1515.
(10) (a) Casadei, M. A.; Inesi, A.; Micheletti Moracci, F.; Rossi, L.
Chem. Commun. 1996, 2575. (b) Casadei, M. A.; Micheletti Moracci,
F.; Zappia, G.; Inesi, A.; Rossi, L. J . Org. Chem. 1997, 62, 6754 and
references therein.
(11) (a) Ikeda, S.; Takagi, T.; Ito, K. Bull. Chem. Soc. J pn. 1987,
60, 2517. (b) Gennaro, A.; Isse, A. A.; Severin, M. G.; Vianello, E.;
Bhugun, I.; Sav e´ ant, J . M. J . Chem. Soc., Faraday Trans. 1996, 92,
3963 and references therein.
1
F. J . Mol. Catal. 1988, 49, 59.
4) (a) Mulla, S. A. R.; Gupte, S. T.; Chaudhari, R. V. J . Mol. Catal.
(
1
1
991, 67, L7. (b) Fukuoka, S.; Chono, M.; Kohno, M. J . Org. Chem.
984, 49, 1458. (c) Fukuoka, S.; Chono, M.; Kohno, M. J . Chem. Soc.
Chem. Commun. 1984, 399. (d) Gupte, S. T.; Chaudhari R. V. J . Catal.
1
988, 114, 246. (e) Abe, Y.; Nagao, Y.; Misono, T. Chem. Express 1988,
, 727.
(
3
5) (a) Aresta, M.; Quaranta, E. Proceeding of the International
Conference on Carbon Dioxide Utilization, Bari; Italy 1993; pp 63-77.
b) Riley, D.; McGhee, W. D.; Waldman, T. ACS Symp. Ser. 1994, 577,
22. (c) Xanding, X.; Moulijn, J . A. Energy Fuels 1996, 10, 305. (d)
Waldman, T. E.; McGhee W. D. J . Chem. Soc. Chem. Commun. 1994,
(
1
9
3
57. (e) McGhee, W. D.; Pan, Y.; Talley, J . J . Tetrahedron Lett. 1994,
5, 839.
(12) Roberts, J . L., J r.; Calderwood, T. S.; Sawyer, D. T. J . Am.
Chem. Soc. 1984, 106, 4667.
(13) (a) Venturello, C.; D’Aloisio, R. Synthesis 1985, 33. (b) Aoyama,
T.; Shina, E.; Ishikawa, J .; Sakurai, N. Eur. Pat. Appl. EP 1986, 269,
949.
(6) (a) Aresta, M.; Quaranta, E. J . Chem. Soc., Dalton Trans. 1992,
1
893. (b) Aresta, M.; Quaranta, E. J . Org. Chem. 1988, 53, 4153. (c)
Belforte, A.; Calderazzo, F. J . Chem. Soc., Dalton Trans. 1989, 1007.
S0022-3263(97)01695-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/30/1998

1
338 J . Org. Chem., Vol. 63, No. 4, 1998
Notes
Ta ble 1. Rea ctivity of TEAHC w ith Differ en t Am in es
a n d Alk yla tin g Rea gen ts
entry
R
R1
R2
X
yielda
1
2
3
4
5
6
7
8
9
0
1
2
3
4
C6H11
C6H11
C6H11
C6H11
C6H11
C6H11
C6H11
PhCH2
Ph(CH2)3
Ph
H
H
H
H
H
H
H
H
H
H
H
Me
H
Et
Br
Br
Br
Br
OTs
OCO2Et
I
I
I
I
I
I
I
I
90
71
i-Pr
t-Bu
Bn
Et
Et
Et
Et
Et
Et
Et
b
92
97
F igu r e 1. Reaction of TEAHC with amines bearing a leaving
group.
b
propylamines, probably because of a competitive self-
alkylation reaction of the substrate (Figure 1).
94
98
94
53
76
85
Under our experimental conditions, the formation of
tetraethylammonium carbamate can be supposed. Keep-
ing in mind the previously noted difficulty in transferring
carbamic ion into alkyl halide substrates, it follows that
the presence of tetraethylammonium ion as counterion
increases the nucleophilicity of oxygen, thus rendering
the O-alkylation reaction prevalent with respect to the
N-alkylation.
1
1
1
1
1
4-MeOPh
PhCH2
CH2dCHCH2
Ph
Et
Et
Et
80
b
Ph
a
Yields (%) refer to isolated carbamate except for entry 5 (GC
yield). b Starting amines were recovered at the end of the reaction.
The reactivity of TEAHC toward a wide range of
aromatic and aliphatic amines and alkylating reagents
opens up the development of a novel, mild, and safe
methodology for the synthesis of linear and cyclic car-
bamates. The mildness of the reaction conditions and
the stability of reagent (if stored under argon TEAHC
has a shelf life of several months), as well as its easy
and cheap preparation, make this procedure a valuable
alternative to the methodologies reported up to now.
Extension of this methodology to other classes of
organic compounds is now under study.
reagents. This procedure afforded the corresponding
carbamates 2 in high to excellent yields (eq 1).
The results are reported in Table 1. The yield of
carbamate is affected by the nature of the alkylating
reagent employed. Cyclohexylamine was used as model
compound (entries 1-7). The corresponding carbamate
was isolated in excellent yields when primary and
benzylic halides were used (entries 1, 4, 7) and in good
yield with isopropyl bromide (entry 2), while it was
absent when a tertiary halide was employed (entry 3).
Also, diethyl carbonate did not furnish the expected
carbamate (entry 6). Ethyl tosylate was reactive, but the
resulting carbamate needed to be separated from the
unreacted starting tosylate present in the solution (entry
Exp er im en ta l Section
Gen er a l. Amines were commercially available; purification
by distillation or crystallization was carried out when necessary.
Dry acetonitrile (Lab-scan, anhydroscan) was used as received.
TEAHC was prepared as reported by Venturello1 starting from
a methanol solution (25% w/w) of TEAOH (Fluka). The reagent
was dried under vacuum for 24 h and then was stored under
argon.
3a
5
).
Rea ction of Am in es w ith TEAHC. Gen er a l P r oced u r e.
Amine (1.0 mmol) was added to a stirred solution of TEAHC
(1.5 mmol) in dry acetonitrile (15 mL). After 1 h, if necessary,
a 5-fold excess of alkylating reagent was added and the reaction
was stirred overnight. The progress of the reaction was moni-
tored by TLC (silica gel, n-hexanes-ethyl acetate 7:3). Solvent
was removed under reduced pressure and the residue extracted
with ether. Flash chromatography, or simple filtration of the
ethereal extracts, afforded the isolation of the carbamate. All
The nucleophilicity of the amine represents another
factor that modifies the reactivity and consequently the
amount of carbamate obtained. Primary (entry 9),
secondary (entry 12), benzylic (entry 8), and allylic (entry
1
3) amines all react in very good yields. Aromatic amines
show a weaker reactivity compared to aliphatic ones. A
moderate yield of carbamate (53%) results from the
reaction of aniline (entry 10), while the reactivity is
remarkably increased (76% yield of carbamate; entry 11)
by the presence of an electron-donating group on the
aromatic ring. The combination of steric and electronic
effects completely inhibits the reaction; as a confirmation,
diphenylamine turned out to be completely unreactive
1
13
the products were fully characterized by H (200 MHz) and
C
NMR (50.3 MHz), MS (EI, 70 eV; CI), melting point, and
comparison with authentic samples,1 wherever possible.
0b
Ack n ow led gm en t. This work was supported by
research grants from MURST and CNR, Rome, Italy.
(entry 14).
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR of
When TEAHC was allowed to react with amines
all the linear and cyclic carbamates obtained (22 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
bearing a leaving group, a different reactivity was
reported; cyclic carbamates were obtained as a result of
an intramolecular nucleophilic substitution. Only mod-
erate yields of oxazolidin-2-one and 1,3-oxazin-2-one were
recovered from the corresponding ω-bromoethyl and
J O971695Y