The synthesis of alkyl carbamates from primary aliphatic amines and dialkyl carbonates in supercritical carbon dioxide

Article abstract of DOI:10.1016/S0040-4039(01)02390-5

At 130°C and in the presence of compressed CO₂, primary aliphatic amines [RNH₂, R=C₁₀H₂₁, C₈H₁₇, cHex, 1-(C₁₀H₇)CH₂] react with organic carbonates (R′OCO

Full text of DOI:10.1016/S0040-4039(01)02390-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1217–1219
The synthesis of alkyl carbamates from primary aliphatic amines
and dialkyl carbonates in supercritical carbon dioxide
Maurizio Selva,* Pietro Tundo and Alvise Perosa
Dipartimento di Scienze Ambientali dell’Universita` Ca’ Foscari, Calle Larga S. Marta, 2137-30123 Venice, Italy
Received 17 October 2001; revised 17 December 2001; accepted 19 December 2001
Abstract—At 130°C and in the presence of compressed CO2, primary aliphatic amines [RNH2, R=C10H21, C8H17, cHex,
1-(C10H7)CH2] react with organic carbonates (R%OCO2R%; R%=Me, Et) to give alkyl carbamates (RNHCO2R%, 1). Although CO2
promotes the reaction also at a low pressure, good yields (ꢀ80%) of 1 are achievable only with supercritical carbon dioxide
(scCO2) at 90 bar, which inhibits the formation of N-methylated by-products. © 2002 Elsevier Science Ltd. All rights reserved.
Organic carbamates (RNHCO2R%, 1) are compounds
widely used for a number of scopes including pharma-
ceutical preparations, production of agrochemicals
(pesticides and herbicides), and more generally, of inter-
mediates for fine and commodity chemicals.1
In particular, very good results have been claimed with
the use of alkyl halides and CO2 [either in the gaseous
or in the supercritical phase (scCO2)], in the presence of
onium salts and basic catalysts [(a) of Scheme 1].5
While, moderate yields of 1 (ꢀ50%) were reported with
dimethyl carbonate and gaseous CO2 [(b) of Scheme
1].6 This latter reaction attracted our attention for a
two-fold reason: (i) DMC is a green reagent;7 (ii) as a
part of our research program on clean syntheses, the
reactivity of DMC—both as a methylating and a
methoxycarbonylating agent of amines—has been
extensively investigated by us.8 Moreover our group is
involved in the study of scCO2 as a solvent.9
By far, the most important reaction for the synthesis of
these products, is the aminolysis of chloroformate esters
obtained from phosgene and alcohols.2 This method
poses great concerns from both the environmental and
safety standpoints because of the toxicity and corrosion
properties of phosgene itself.3
To overcome this drawback, many alternative routes
with low environmental impact have been conceived.
Among them, the catalytic carbonylation of nitroaro-
matics and the oxidative carbonylation of amines
should be noted,4 as well as the even more eco-friendly
procedures based upon the reaction of amines with
carbon dioxide in the presence of alkyl halides5 or
dimethyl carbonate (DMC) (Scheme 1).6
We wish to report here that a convenient procedure for
the carbamation of primary aliphatic amines with
dialkyl carbonates can be performed in supercritical
carbon dioxide (Table 1).
Caution: operation of high-pressure equipment requires
proper safety precautions to minimise the risks of per-
sonal injury.11
R'X
RNHCO2R'
(R' = n-Pr, n-Bu, Bn) (a)
CO2
In a typical procedure, a 150 mL stainless steel auto-
clave fitted with a thermostatic jacket was charged with
n-decylamine (1.0 g, 6.3 mmol) and DMC (5.7 g,
6.4×10−2 mol). The autoclave was then pressurised with
CO2 (SFC/SFE grade) at approximately 40 bar, by
using an automatic syringe pump (ISCO model 260 D),
and it was heated to the desired temperature, through
an oil-circulating thermostat. The final pressure of 90
bar was reached by slowly adding the remaining CO2 to
the reactor. The mixture was magnetically stirred
RNH2
DMC
RNHCO2Me
(b)
Scheme 1.
* Corresponding author. Fax: +39 041 234 8620; e-mail:
selva@unive.it
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02390-5

1218
M. Sel6a et al. / Tetrahedron Letters 43 (2002) 1217–1219
a
Table 1. The carbamation of primary aliphatic amines with dialkyl carbonates in scCO2
Entry
Substrate
RNH2
Organic
Carbonate
T (°C)
Reaction time (h)
Conv’n (%)
Product RNHCO2R%,
Isolated yield (%)
10
1
2
3
R: C10H21
R: C10H21
DMC
DEC
DMC
130
130
130
17
20
20
95b
80
91
1a: R=Me
1b: R=Et
1c: R=Me
83
65
80
CH2
R:
4
5
6
DEC
DMC
DMC
140
130
130
18
15
14
65
89
85
1d: R=Et
1e: R=Me
1g: R=Me
48
77
50
R: C8H17
R: cHex
a All reactions were performed at 90 bar, using a dialkyl carbonate/substrate molar ratio of 10. DEC: diethyl carbonate.
b At 130 bar, conversion was 96%.
DMC
throughout the reaction which was allowed to proceed
+
RNHCO2- RNH3
2RNH2 + CO2
RNHCO2Me
for the reported time (entry 1). After cooling, CO2 was
slowly vented by bubbling it into diethyl ether (5 mL).
2
(1)
However, in conventional solvents or in DMC as a
reagent/solvent, results are modest: for instance, after
24 h at 90°C, cyclohexyl- and allyl-amines were
reported to give the corresponding methyl urethanes in
35 and 55% yields.6a
The content of the autoclave was washed with addi-
tional diethyl ether (5 mL), and the combined ethereal
solutions were acidified (HCl 10%, 10 mL), extracted,
and finally dried over Na2SO4. After filtration and
rotary evaporation, compound 1a was recovered as a
yellow solid (1.15 g, 5.34 mmol; 83%) which was
analysed by GC/MS (HP 5890, series II, fitted with a 30
As can be seen from Table 1, in the presence of
supercritical carbon dioxide, the carbamation reactions
with DMC proceed with good yields (77–83%: entries 1,
3, and 5; except for cHex: 50%, entry 6), towards the
formation of the corresponding methyl carbamates.
Results also show that diethyl carbonate (DEC) is
suitable for the preparation of ethyl carbamates (entries
2 and 4). However, lower conversions are due to the
lower reactivity of DEC with respect to DMC,15 and
yields have not been optimised.
1
m HP5MS column) and HNMR (Bruker 300 MHz).
The structure was also confirmed by comparison with
an authentic sample obtained by reported procedures.12
Although the carbamation of amines with dialkyl car-
bonates is known,13a only catalysed reactions proceed
with good yields and selectivities;12 more recently, good
results have been reported with Pb- and alumina-based
catalysts.13b,c Instead, as mentioned above in Scheme 1,
the uncatalysed process may take place in the presence
of gaseous carbon dioxide through the formation of
alkylammonium carbamates (2), (Eq. (1))14 which
appear as convenient nucleophilic precursors of alkyl
carbamates.
To investigate more in-depth the role of carbon diox-
ide, n-decylamine was made to react with DMC at
130°C and at different pressures of CO2 (from 8 to 90
bar). Reactions were run also at different times (3, 6
and 14 h). Results are reported in Table 2.
Table 2. The reaction of n-C10H21NH2 with DMC at different pressure of carbon dioxidea
Entry
Pressure of CO2 (bar)
Reaction time (h)
Conv’n (%, GC) Ratio of carbamate
Isolated yield of 1a (%)
products (%)b
1a
2a16
1
2
3
4
5
6
7
8
8
8
8
19
19
40
90
90
3
6
14
6
14
6
6
74
100
100
100
100
100
100
100
87
76
74
82
83
87
96
90
13
24
26
18
17
13
4
Ndc
54
51
57
58
68
77
76
14
10
1a: n-C10H21NHCO2Me; 2a: n-C10H21N(Me)CO2Me.
a Reactions carried out with a DMC/n-C10H21NH2 molar ratio of 10.
b Ratio determined by GC.
c Not determined.

M. Sel6a et al. / Tetrahedron Letters 43 (2002) 1217–1219
1219
The carbamation reaction may take place also at a low
pressure (8 bar, entries 1–3), though under such condi-
tions, a competitive methylation process occurs and a
mixture of n-C10H21NHCO2Me (1a) and its N-methyl
derivative [n-C10H21N(Me)CO2Me, 2a] is recovered.
After 6 h, the ratio 1a:2a is 76:24 (entry 2), and even at
a lower conversion (74%, 3 h), it does not exceed 87:13
(entry 1). Prolonged reaction times do not alter signifi-
cantly the product distribution, suggesting that 2a
comes mainly from the N-methylated amine rather than
1a (entries 3 and 5). However, as the CO2 pressure is
increased, the carbamation selectivity is enhanced as
well, up to 96% at 90 bar (entry 7). The effect of the
solvent pressure results in the inhibition of the methyla-
tion reaction,17 which is advantageous for the forma-
tion of pure carbamates 1.
Green Chemistry: Designing Chemistry for the Environ-
ment; Anastas, P.; Williamson, T., Eds.; ACS Symposium
Series No. 626, 1996; Chapter 6, pp. 70–80.
8. (a) Trotta, F.; Tundo, P.; Moraglio, G. J. Org. Chem.
1987, 52, 1300; (b) Selva, M.; Bomben, A.; Tundo, P. J.
Chem. Soc., Perkin Trans. 1 1997, 1041; (c) Selva, M.;
Tundo, P.; Perosa, A. J. Org. Chem. 2001, 66, 677; (d)
Berto, C. Thesis, University of Ca’ Foscari, Venezia
(Italy), 2001.
9. DeSimone, J. M.; Selva, M.; Tundo, P. J. Org. Chem.
2001, 66, 4047.
10. Compound 1a: 1H NMR (CDCl3) l: 0.89 (t, 3H, CH3,
J=6.5 Hz), 1.27 (m, 14H, 7CH2), 1.49 (m, 2H, CH2),
3.16 (q, 2H, CH2N, J=6.4 Hz), 3.67 (s, 3H, OCH3), 4.66
(brs, 1H, NH); GC/MS (70 eV) m/z (relative intensity):
215 (M+, 4), 200 (3), 88 (100), 76 (17), 44 (13).
Compound 1b: 1H NMR (CDCl3) l: 0.89 (t, 3H, CH3,
J=6.7 Hz), 1.27 (m, 17H, 7CH2 and 1CH3), 1.49 (m, 2H,
CH2), 3.17 (q, 2H, CH2N, J=6.7 Hz), 4.11 (q, 2H,
OCH2, J=6.8 Hz), 4.62 (brs, 1H, NH); GC/MS (70 eV)
m/z (relative intensity): 229 (M+, 6), 200 (20), 102 (100),
90 (17), 41 (15).
In conclusion, the reported procedure is an example of
a genuinely clean synthesis of alkyl carbamates using
eco-friendly reagents without any catalysts or addi-
tional co-solvents. The efficiency of the method lies in
the use of compressed CO2 whose pressure must be
high enough (ꢀ90 bar) to favour the formation of
alkylammonium carbamates 2 (Eq. (1)), thus leading to
a substantial inhibition of N-methylated by-products.
However, solvation effects may also have a role: in fact,
at a higher CO2 pressure [130 bar, footnote (b) in the
Table 1], the conversion does not vary, meaning that a
higher concentration of the reactant CO2 does not
accelerate the reaction.
1
Compound 1c: H NMR (CDCl3) l: 1.67 (brs, 1H, NH),
3.73 (s, 3H, OCH3), 4.83 (d, 2H, CH2, J=5.5 Hz),
7.4-8.05 (m, 7H, Ar); GC/MS (70 eV) m/z (relative
intensity): 216 (12), 215 (M+, 81), 201 (12) 200 (87), 156
(60), 155 (21), 154 (51), 141 (60), 129 (100), 128 (48), 127
(48), 115 (48).
Compound 1d: 1H NMR (CDCl3) l: 1.25 (t, 3H, CH3,
J=6.9 hz), 1.61 (brs, 1H, NH), 4.16 (q, 2H, OCH2,
J=6.9 Hz), 4.83 (d, 2H, CH2, J=5.6 Hz), 7.40-7.90 (m,
7H, Ar); GC/MS (70 eV) m/z (relative intensity): 230 (8),
229 (M+, 49), 201 (15), 200 (100), 183 (12), 156 (62), 155
(12), 154 (32), 141 (48), 129 (93), 128 (34), 127 (33), 115
(32).
References
1. (a) Tai-Teh, W.; Huang, J.; Arrington, N. D.; Dill, G. M.
J. Agric. Food Chem. 1987, 35, 817; (b) Rivetti, F.;
Romano, U.; Sasselli, M. US Pat. 4514339, ECS 1985; (c)
Kato, T.; Suzuki, K.; Takahashi, J.; Kamoshita, K. J.
Pesticide Sci. 1984, 9, 489; (d) Aresta, M.; Quaranta, E.
Chem. Tech. 1997, 3, 32; (e) Greene, T. W.; Wuts, P. G.
M. Protective Groups in Organic Synthesis, 3rd ed.; Wiley
& Sons: New York, 1999.
2. Babad, H.; Zieler, A. G. Chem. Rev. 1973, 73, 75.
3. Matlack, A. Introduction to Green Chemistry; M. Dekker,
2001; pp. 27–45.
4. (a) Cenini, S.; Pizzetti, M.; Crotti, C. In Aspects of
Homogeneous Catalysis; Ugo, R., Ed.; Riedel: Dordrecht,
The Netherlands, 1998; Vol. 6, pp. 97–108; (b) Aresta,
M.; Giannoccaro, P.; Tommasi, I. J. Organomet. Chem.
1994, 476, 13.
Compounds 1e and 1f: full characterisation data are in
Refs. 13c and 6a, respectively.
11. Jessop, P. G.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1996, 118, 345.
12. Bortnick, N.; Luskin, L. S.; Hurwitz, M. D.; Rytina, A.
W. J. Am. Chem. Soc. 1956, 78, 4358.
13. (a) Cahours, A. Ann. 1845, 56, 266; (b) Fu, Z.-H.; Ono,
Y. J. Mol. Catal. 1994, 91, 399; (c) Vauthey, I.; Valot, F.;
Gozzi, C.; Fache, F.; Lemaire, M. Tetrahedron Lett.
2000, 6347.
14. Caplow, M. J. Am. Chem. Soc. 1968, 90, 6795.
15. Selva, M.; Marques, C. A.; Tundo, P. J. Chem. Soc.,
Perkin Trans. 1 1994, 1323.
16. Compound 2a: GC/MS (70 eV) m/z (relative intensity):
229 (M+, 8), 102 (100), 88 (19), 58 (18), 42 (18), 41 (29).
The structure of 2a was confirmed by reacting n-
C10H21NHMe with ClCO2Me according to known proce-
dures (Bortnick, N.; Luskin, L. S.; Hurwitz, M. D.;
Rytina, A. W. J. Am. Chem. Soc. 1956, 78, 4358).
17. DMC is an excellent N-methylating agent at tempera-
tures over 130°C (Ref. 8).
5. (a) Yoshida, M.; Hara, N.; Okuyama, S. Chem. Commun.
2000, 151; (b) Salvatore, R. N.; Shin, S., II; Nagle, A. S.;
Jumg, K. W. J. Org. Chem. 2001, 66, 1035.
6. (a) Aresta, M.; Quaranta, E. Tetrahedron 1991, 47, 9489;
(b) Aresta, M.; Dibenedetto, A.; Quaranta, E.; Boscolo,
M.; Larrson, R. J. Mol. Catal. 2001, 174, 7.
7. (a) Shaik, A.-A. G.; Sivaram, S. Chem. Rev. 1996, 96,
951; (b) Rivetti, F.; Romano, U.; Delledonne, D. In