The reaction of amines with an electrogenerated base. Improved synthesis of arylcarbamic esters

Article abstract of DOI:10.1016/S0040-4039(99)02180-2

The electrogenerated base of 2-pyrrolidone reacts with amines and anilines yielding the corresponding alkyl and aryl carbamates, after addition of carbon dioxide and ethyl iodide. Arylcarbamic esters are obtained in very good yields under mild reaction conditions with respect to the methods so far reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02180-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 963–966
The reaction of amines with an electrogenerated base.
Improved synthesis of arylcarbamic esters
Marta Feroci, Achille Inesi and Leucio Rossi a
b
a,∗
a
Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università degli Studi, Monteluco di Roio, I-67040,
L’Aquila, Italy
b
Dipartimento di ICMMPM, Università degli Studi ‘La Sapienza’, Via del Castro Laurenziano 7, I-00161, Roma, Italy
Received 30 September 1999; accepted 24 November 1999
Abstract
The electrogenerated base of 2-pyrrolidone reacts with amines and anilines yielding the corresponding alkyl and
aryl carbamates, after addition of carbon dioxide and ethyl iodide. Arylcarbamic esters are obtained in very good
yields under mild reaction conditions with respect to the methods so far reported. © 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: amines; carbamates; carboxylation; electrogenerated bases.
Organic carbamates find several applications in the chemical, pharmaceutical and agricultural indus-
tries in the syntheses of intermediates, polymers, medical drugs, pesticides, herbicides and fungicides.1
In classical organic syntheses, this class of compounds finds extensive utilization as protecting groups
2
of the amine functionality in the preparation of polypeptides or other natural substances. Consequently,
alternative syntheses of carbamates to the classical methods, which employ toxic and corrosive reagents
like phosgene and its derivatives, have been studied and proposed in the last few years.3
Our research group is engaged in the electrochemical synthesis of carbamic esters using carbon dio-
xide, a cheap and abundant reagent, as a raw material and potential source of carbon. We found that linear
and cyclic carbamates may be obtained by reaction of electrochemically generated tetraethylammonium
carbonate (TEAC) and tetraethylammonium peroxodicarbonate (TEAPC) with aryl and alkyl amines,
followed, if necessary, by the addition of a suitable alkylating reagent. TEAC and TEAPC were obtained
4
a
by electrolysis carried out in solutions (MeCN–Et NClO ) saturated with CO (E=−2.1 V versus SCE)
4
4
2
4
b,c
or with a mixture of O –CO
(E=−1.0 V versus SCE). Both methods provide carbamates in good to
2
2
excellent yields. Aryl amines were found to be less reactive than the corresponding aliphatic ones.
+
The electrochemical reduction of CO to CO2 , in aprotic solvents, involves three competing pa-
thways yielding oxalate, carbonate (plus CO in equimolar amounts) and formate anions. The product
2
5
∗
Corresponding author. Tel: +39 0862 434216; fax: +39 0862 434203; e-mail: inesi@ing.univaq.it (A. Inesi)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02180-2
tetl 16108

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distribution is strongly affected by the cathodic material, the current density and the concentration of
CO and H O. Consequently, the selective formation of TEAC requires careful choice and control of the
2
2
6
conditions of electrolysis. Moreover, the weak oxidizing power of TEAPC solutions has been observed
by several authors. Therefore, the use of TEAPC as a carboxylating agent towards aminic substrates
7
containing easily oxidizable functional groups is not recommended.
Here we present a novel electrochemical synthesis of alkyl- and arylcarbamic esters that does not
resort to the direct reduction of CO or O . This synthesis is based upon the reaction of amines and
2
2
+
8
anilines with a 2-pyrrolidone electrogenerated base (associated with the Et N cation) (2) followed
4
by sequential addition of carbon dioxide and ethyl iodide (Scheme 1). Electrogenerated bases (EGBs)
are usually obtained by cathodic reduction of appropriate precursors (not necessarily bases), the so-
called probases (PBs) (e.g. azocompounds, activated alkenes, oxygen, 2-pyrrolidone). The widespread
9
applications of electrogenerated bases in electro-organic synthesis have been extensively reviewed and
new possible utilizations have been recently suggested.10
Scheme 1. Reaction of amines with the EGB of 2-pyrrolidone
The EGB was obtained by reduction of 2-pyrrolidone on a Pt cathode under galvanostatic control.8
The anion 2 was able to deprotonate different aliphatic and aromatic amines yielding the corresponding
†
tetraethylammonium amides or anilides, which can then react with carbon dioxide and EtI to give the
required carbamate. The yield of carbamate was affected by different parameters including the molar
ratio pyrrolidone:amine and the number of faradays per mole of probase supplied to the electrodes. Some
results are reported in Table 1, entries 1–9. The highest yields for ethyl cyclohexyl carbamate were
obtained when a molar ratio of pyrrolidone:amine of 2:1 and 1.5 F per mole of probase were used (entry
6). As reported in Table 1, the reaction with anilines allows arylcarbamic esters to be obtained in very
good yields, especially if compared with the results of our previous methods employing TEAC, TEAPC,
or with the other ‘phosgene-free’ methods reported in the literature.3
,4a,b,12
In any case, the reaction
yields were affected by the nature and the position of the substituent (either EWG or EDG) present on
the aromatic ring.
−
1
In a typical experiment, a solution of 1 (2.0 mmol) in acetonitrile 0.1 mol L in tetraethylammonium
perchlorate (20 mL) was electrolyzed, under Ar, at 0°C, in a divided cell (Pt anode and cathode) under
−
2
−1
galvanostatic control (I=25 mA cm ). After the flow of 1.5 F mol of PB, the solution was warmed
to room temperature and the amine (1.0 mmol) was added. The reaction mixture was stirred under Ar
for an additional 15 min, and then carbon dioxide was bubbled into the stirred solution for 1 h, followed
4
by the addition of a fivefold molar excess of ethyl iodide. The usual work-up gave the corresponding
carbamates according to the reaction yields reported in Table 1.
†
Several tetraethylammonium anilides (e.g. tetraethylammonium diphenylamide) have been isolated and characterized.11

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Table 1
Reaction of alkyl and aryl amines (1.0 mmol) with 2-pyrrolidone (PB), CO
different reaction conditions
2
and EtI (5.0 mmol) under
In conclusion, a new electrochemical methodology that allows the synthesis of carbamates from
primary and secondary amines and CO in high yields, under mild conditions and avoiding the use of
2
toxic and hazardous chemicals, has been designed and set up. The carboxylation of amine substrates, in
+
solutions containing large counter-ions such as Et N , is made possible by the deprotonating action of
4
a 2-pyrrolidone electrogenerated base (2) under the reported conditions. The aryl carbamates have been
obtained in remarkably high yields in comparison to the previously reported methods.
Acknowledgements
This work was supported by research grants from M.U.R.S.T. and C.N.R., Rome, Italy.

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References
1
. (a) Adams, P.; Baron, F. A. Chem. Rev. 1965, 65, 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. (NY) 1996, 77 (Handbook of
Food Analysis, Vol. 2) 1501.
2
3
4
. Greene, T.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; John Wiley & Sons: New York, 1991; pp.
3
15–348.
. Aresta, M.; Quaranta, E. Proceeding of the International Conference on Carbon Dioxide Utilization; Bari, Italy, 1993; pp.
3–77 and references cited therein.
6
. (a) Casadei, M. A.; Inesi, A.; Micheletti Moracci, F.; Rossi, L. Chem. Commun. 1996, 2575–2576. (b) Casadei, M. A.;
Micheletti Moracci, F.; Zappia, G.; Inesi, A.; Rossi, L. J. Org. Chem. 1997, 62, 6754–6759. (c) Roberts Jr., J. L.; Calderwood,
T. S.; Sawyer, D. T. J. Am. Chem. Soc. 1984, 106, 4667–4670.
5
6
. Amatore, C.; Savéant, J. M. J. Am. Chem. Soc. 1981, 103, 5021–5023.
. (a) Ikeda, S.; Takagi, T.; Ito, K. Bull. Chem. Soc. Jpn. 1987, 60, 2517–2522. (b) Gennaro, A.; Isse, A. A.; Severin, M. G.;
Bhugun, I.; Savéant, J. M. J. Chem. Soc. Faraday Trans. 1996, 92, 3963–3968 and references cited therein.
. (a) Nagano, T.; Yamamoto, H.; Hirobe, H. J. Am. Chem. Soc. 1990, 112, 3529–3535. (b) Casadei, M. A. Unpublished results.
. Shono, T.; Kashimura, S.; Nogusa, H. J. Org. Chem. 1984, 49, 2043–2045.
7
8
9
. (a) Baizer, M. M. In Electrogenerated Bases and Acid in Organic Electrochemistry; Lund, H.; Baizer, M. M., Eds.; Dekker:
New York, 1991; pp. 1265–1282 and references cited therein. (b) Utley, J. H. P. Electrogenerated Bases. In Topics in Current
Chemistry; Vol. 142 (Electrochemistry I); Springer-Verlag: Berlin, 1987; pp. 131–165 and references cited therein.
1
0. (a) Barhdadi, R.; Simsen, B.; Troupel, M.; Nédélec, J. Y. Tetrahedron 1997, 53, 1721–1728. (b) Bonafoux, D.; Bordeau,
M.; Biran, C.; Cazeau, P.; Dunogués, J. J. Org. Chem. 1996, 61, 5532–5536.
1
1
1
1. Jolly, W. L. J. Am. Chem. Soc. 1955, 77, 4958–4960.
2. Yoshida, Y.; Ishii, S.; Kawato, A.; Yamashita, T.; Yano, M.; Inoue, S. Bull. Chem. Soc. Jpn. 1988, 61, 2913–2916.
1
3. Ethyl 3-bromo-4-methylphenyl carbamate. H NMR (CDCl
3
, 200 MHz) δ: 7.40 (d, 1H, J=8.6 Hz, Ar); 7.28 (d, 1H, J=2.5
CH ), 2.34 (s, 3H, PhCH ); 1.29 (t,
, 50.3 MHz) δ: 153.4, 138.5, 137.1, 132.6, 120.8, 118.4, 117.6, 61.3, 22.9, 14.5.
GC–MS m/z: 259 (100); 257 (94); 200 (32); 198 (27); 187 (34); 185 (38); 105 (42); 104 (24); 77 (36); 51 (26). Anal. calcd
for C10 12BrNO : C, 46.53; H, 4.69. Found C, 46.41; H, 4.76.
Hz, Ar); 7.06 (dd, J=2.5; 8.6 Hz, Ar); 6.51 (brs, 1H, NH); 4.20 (q, 2H, J=7.1 Hz, CH
2
3
3
13
3
2 3 3
H, J=7.1 Hz, CH CH ). C NMR (CDCl
H
2