Cya n om eth yl An ion /Ca r bon Dioxid e
System : An Electr ogen er a ted
Ca r boxyla tin g Rea gen t. Syn th esis of
Ca r ba m a tes u n d er Mild a n d Sa fe
Con d ition s
(phosgene, isocyanates, etc.) with all the drawbacks that
these reagents imply. Therefore, much effort has been
devoted to the development of safer alternative synthetic
4
methods that avoid the use of these harmful chemicals.
In this context, several authors suggested the utiliza-
tion of carbon dioxide, a cheap and abundant reagent,
as a safe substitute of phosgene.5
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Monica Orsini, Laura Palombi, and Achille Inesi*
Recently, J ung et al. reported a synthesis of carbam-
6
ates via a cesium base-promoted method, which allows
Dip. Chimica, Ingegneria Chimica e Materiali,
Universit a` degli Studi, I-67040,
for the efficient coupling of amines with halides in the
presence of TBAI (tetrabutylammonium iodide) and CO
in DMF solutions.
2
Monteluco di Roio, L’Aquila, Italy,
Dip. Ingegneria Chimica, Materiali,
Materie Prime e Metallurgia, Universit a` “La Sapienza”,
via Castro Laurenziano, 7, I-00161 Roma, Italy, and
Dip. di Studi di Chimica e Tecnologia delle Sostanze
Biologicamente Attive, Universita’ “La Sapienza”,
P.le Aldo Moro, 5, I-00185 Roma, Italy
We already described possible electrochemical routes
for the synthesis of carbamates.7 At present, we are
,8
(
3) (a) Kato, T.; Suzuki, K.; Takahashi, J .; Kamoshita, K. J . Pesticide
Sci. 1984, 9, 489-495. (b) Picardi, P. Chim. Ind. 1986, 68, 108-117.
c) Barthelemy, J . Lyon Pharm. 1986, 37(5), 249-263. (d) Tai-The, W.;
Huang, J .; Arrington, N. D.; Dill, G. M. J . Agric. Food Chem. 1987,
5, 817-823. (e) The Pharmacological Basis of Therapeutics, 8th ed.;
(
Received October 24, 2002
3
Goodman, L., Gilman, A., Rall, T. W., Nies, A. S., Taylor, P., Eds.;
Pergamon Press: NewYork, 1990. (f) Mateen, A.; Chapalamadugu, S.;
Kashar, B.; Batthi, A. R.; Chaudry, G. R. Biol. Degrad. Biorem. Toxic.
Chem. 1994, 198-233. (g) The Pesticide Manual, 10th ed.; Tomlin, C.
D. S., Ed.; Crop Protection Publication: Farnham, U.K., 1994. (h)
Wigfield, Y. Y. Food Sci. Technol. (N.Y.) 1996, 77 (Handbook of Food
Analysis, Vol. 2), 1501-1529.(i) Alexander, J .; Bindra, D. S.; Glass, J .
D.; Holahan, M. A.; Renyer, M. L.; Rork, G. S.; Sitko, G. R.; Stranieri,
M. T.; Stupienski, R. F.; Veerapanane, H.; Cook, J . J . J . Med. Chem.
-
Abstr a ct: A new carboxylating reagent ( CH2CN/CO2) was
obtained by bubbling CO2 in a CH3CN-TEAP (tetraethy-
lammonium perchlorate) solution previously electrolyzed
under galvanostatic control. Organic carbamates were iso-
lated from these solutions after addition of amines and an
alkylating agent. In this paper, we describe the optimized
conditions for the electrochemical synthesis of carbamates
from amines and CO2, in mild and safe conditions, without
any addition of bases, probases, or catalysts. Carbamates
were isolated from primary and secondary aliphatic amines
in high to excellent yields and from aromatic amines in
moderate yields (dependent on the nucleophilicity of the
nitrogen atom).
1
996, 39, 480-486. (j) Barbachyn, M. R.; Hutchinson, D. K.; Brickner,
S. J .; Cynamon, M. H.; Kilburn, J . O.; Klemens, S. P.; Glickman, S.
E.; Grega, K. C.; Hendges, S. K.; Toops, D. S.; Ford, C. W.; Zurenko,
G. E. J . Med. Chem. 1996, 39, 680-685.
(4) (a) Fukuoka, S.; Chono, M.; Kohno, M. J . Org. Chem. 1984, 49,
1
458-1460. (b) Fukuoka, S.; Chono, M.; Kohno, M. J . Chem. Soc.,
Chem. Commun. 1984, 399-400. (c) Gupte, S. P.; Chaudhari, R. V. J .
Catal. 1988, 114, 246-258. (d) Abe, Y.; Nagao, Y.; Misono, T. Chem.
Express 1988, 3, 727-730. (e) Bender, R.; Braunstein, P.; De Bellefon,
C. D. M. Polyhedron 1988, 7, 2271-2283. (f) Cenini, S.; Pizzotti, M.;
Crotti, C.; Ragaini, F.; Porta, F. J . Mol. Catal. 1988, 49, 59-69. (g)
Belforte, A.; Belli D’Amico, D.; Calderazzo, F. Chem. Ber. 1988, 121,
1891-1897. (h) Leconte, P.; Metz, F.; Mortreux, A.; Osborn, J . A.; Paul,
F.; Petit, F.; Pillot, A. J . Chem. Soc., Chem. Commun. 1990, 22, 1616-
In the past decades, the study of organic carbamates
reactivity, synthetic methodologies, applications) re-
ceived special attention, and new contributions are now
(
1
1
617. (i) Mulla, S. A. R.; Gupte, S. T.; Chaudhari, R. V. J . Mol. Catal.
991, 67, L7-L10. (j) J akus, V.; Bojsova, E. Collect. Czech. Chem.
available through several articles.
Commun. 1992, 57, 1505-1515. (k) Ragaini, F.; Cenini, S.; Demartin,
F. J . Chem. Soc., Chem. Commun. 1992, 1467-1468. (l) Romano, V.
Chim. Ind. (Milan) 1993, 75, 303-306. (m) Ragaini, F.; Cenini, S.
Chim. Ind. (Milan) 1996, 78, 421-427. (n) Tafesh, A. M.; Weiguny, J .
Chem. Rev. 1996, 96, 2035-2052. (o) Ragaini, F.; Cenini, S. J . Mol.
Catal. A Chem. 1996, 109, 1-25. (p) Gupte, S. P.; Shivarkar, A. B.;
Chaudhari, R. V. J . Chem. Soc., Chem. Commun. 2001, 2620-2621.
Organic carbamates1 are a class of compounds of
growing interest because of their multiple applications
as protective groups for the amine function of amino acids
2
in peptide chemistry. In addition, they play a noticeable
role in the synthesis of pharmaceuticals (medicinal drug),
agricultural chemicals (pesticides, fungicides, herbicides)
and in the chemical industry (starting materials, inter-
(
q) de Leon, R. G.; Yamanaka, I.; Otsuka, K. Chem. Lett. 2002, 764-
765. (r) Selva, M.; Tundo, P.; Perosa, A. Tetrahedron Lett. 2002, 43,
217-1219. (s) P e´ rez, E. R.; Odnicki da Silva, M.; Costa, V. C.;
Rodrigues-Filho, U. P.; Franco, D. W. Tetrahedron Lett. 2002, 43,
1
3
mediates, solvents, etc.).
4
091-4093. (t) Curini, M.; Epifano, F.; Maltese, F.; Rosato, O.
The classical syntheses of carbamates1 involve the
direct or indirect utilization of toxic and harmful reagents
Tetrahedron Lett. 2002, 43, 4895-4897. (u) Chaturvedi, D.; Kumar,
A.; Ray, S. Synth. Commun. 2002, 32, 2651-2655.
(5) (a) Aresta, M.; Quaranta, E. Proceedings of the International
Conference on Carbon Dioxide Utilization; Bari, Italy, 1993; Depart-
ment of Chemistry, University of Bari: Bari, 1993; pp 63-77. (b) Riley,
D.; McGhee, W. D.; Waldman, T. E. ACS Symp. Ser. 1994, 577, 122-
132. (c) Waldman, T. E.; McGhee, W. D. J . Chem. Soc., Chem. Commun.
1994, 957-958. (d) McGhee, W. D.; Pan, Y.; Talley, J . J . Tetrahedron
Lett. 1994, 35, 839-842. (e) Xanding, X.; Moulijn, J . A. Energy Fuels
1996, 10, 305-325.
(6) (a) Salvatore, R. N.; Shin, S. I.; Nagle, A. S.; J ung, K. W. J . Org.
Chem. 2001, 66, 1035-1037. (b) Salvatore, R. N.; Ledger, J . A.; J ung,
K. W. Tetrahedron Lett. 2001, 42, 6023-6025. (c) Salvatore, R. N.; Chu,
F.; Nagle, A. S.; Kapxhiu, E. A.; Cross, R. M.; J ung, K. W. Tetrahedron
2002, 58, 3329-3347 and references therein.
*
To whom correspondence should be addressed. Fax. +39 06
4
9766749. E-mail: (A.I.) inesi@ing.univaq.it.
†
Dip. ICMMPM, Universit a` “La Sapienza”.
Dip. CTSBA, Universit a` “La Sapienza”.
University of L’Aquila.
‡
§
(
(
1) Adams, P.; Baron, F. A. Chem. Rev. 1965, 65, 567-602.
2) (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons: New York, 1991; pp 315-
48. (b) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; J ohn Wiley and Sons: New York, 1999; pp 503-
50.
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0.1021/jo0266036 CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/21/2003
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J . Org. Chem. 2003, 68, 1548-1551