economy (AE) of 44% and a mass index (MI) of 4.8.15 Both
metrics are better than those of conventional methylating agents
such as dimethyl sulfate (AE: 28%, MI: 18.5,16) and methyl
iodide (AE: 41%, MI: 8.3,17).
Experimental Section
Carbonates 1a-c were prepared following our previous procedures:
2d,e,h,8
transesterification of DMC (350 mL, 4.15 mol) was carried
out with triethylene glycol, diethylene glycol, and ethylene glycol
monomethyl ether in the presence of K2CO3 (DMC/alcohol/K2CO3
in a 7:1:1.5 molar ratio).
N,N-Dimethylation of Anilines. In a 10 mL glass reactor
equipped with condenser, a mixture of the amine (5a-g, 6a,b, and
7a: 4.0 mmol), the methyl alkyl carbonate (8.8 mmol; 1a; 1.95 g;
1b: 1.56 g; 1c: 1.18 g), and an onium- or imidazolium-type salt
(3a-d and 4a,b; 0.1-1 molar equiv with respect to the reactant
amine; Tables 1-3, Figure 1, and Scheme 6) was set to react at
115-170 °C, with stirring. At intervals, samples of the mixture
were analyzed by GC and GC/MS. N,N-Dimethylanilines (com-
pounds Dx of Tables 1-3) were then isolated by FCC.
Physical and spectroscopic properties of carbonates 1a-c and
of amines Dx are reproted in the Supporting Information. IR spectra
(Figure 2) were recorded at room temperature on KBr disks.
Acknowledgment. MIUR (Italian Ministry of University and
Research) is gratefully acknowledged for financial support. Mr.
Alessandro Baldan is also acknowledged for his help with IR
spectra.
Supporting Information Available: 1H and 13C NMR of
carbonates 1a-c, 1H NMR of N,N-dimethylanilines (Tables 1 and
2), and GC/MS spectrum of N-ethyl-N-methyl-m-toluidine. This
material is available free of charge via the Internet at http://
pubs.acs.org.
FIGURE 2. Overlap of IR spectra of pure p-toluidine (5b, black),
pure Ph3PEtI (3a, red), and a mixture of 5b and 3a (blue), recorded at
room temperature: (a) enlargement between 3500 and 3150 cm-1; (b)
JO060674D
enlargement between 1350 and 1150 cm-1
.
(11) (a) Chatt, J.; Duncanson, L. A.; Venanzi, L. M. J. Chem. Soc. 1956,
2712-2725. (b) Sato, H.; Arase, S.-I. Bull. Chem. Soc. Jpn. 1976, 49, 1-7.
(c) Abasbegovic´, N.; Colombo, L.; Bleckmann, P. J. Raman Spec. 1977, 6,
92-99. (d) Sato, H.; Kusumoto, Y.; Arase, S.-I.; Suenaga, M.; Kammura,
S. J. Phys. Chem. 1978, 82, 66-68.
It should be noted that the salt 3a did not substantially adsorb
between 3500 and 3150 cm-1 and between 1300 and 1220 cm-1
(Figure 2a,b, red profiles). The IR spectra of mixtures of 1a
and salts 3a and 3b were merely the overlap of those of the
pure components.
(12) D’Anna, F.; Frenna, V.; Pace, V.; Noto, R. Tetrahedron 2006, 62,
1690-1698.
(13) Both steric and electronic effects associated to oxyethylene chains
of carbonates 2a-c are responsible for the lack of electrophilic reactivity
of these groups (see refs 2). Accordingly, alkyl derivatives [ArNHR and
ArN(Me)R] are always observed in low amounts.
(14) (a) Ono, Y. J. Mol. Catal. 1994, 91, 399-405. (b) Aresta, M.;
Quaranta, Chemtech 1997, 32-40. (c) Fu. Y.; Baba, T.; Ono, Y. J. Catal.
2001, 197, 91-97 (d) Distaso, M.; Quaranta, E. J. Catal. 2004, 228, 36-
42. (e) Yoshida, T.; Sasaki, M.; Hirata, F.; Kawamani, Y.; Inazu, K.;
Ishikawa, A.; Murai, K.; Echizen, T.; Baba, T. Appl. Catal. A: Gen. 2005,
289, 174-178.
This IR investigation indicated that vibrational modes of
amines were perturbed by the onium salts. A similar situation
was also reported by different authors for the adsorption of
anilines over Lewis acidic materials such as aluminum halides.11b,d
More recent NMR and UV investigations also demonstrated that
an acid-base equilibrium can be detected between ionic liquids
of the imidazolium type (e.g., [BMIM][BF4]) and aliphatic
amines.12 An interaction between weak Lewis-acidic phospho-
nium salts and anilines, could account for these results, and for
the selectivity observed in the reaction. Coordination of the
bulky onium cation with the amine group of anilines, could
increase the steric hindrance around the NH2 and make the
nucleophilic attack of the amine easier on the methyl rather than
on the carbonyl carbon of the carbonate.13
To sum up, a general procedure is described for the N,N-
dimethylation of aromatic amines, even deactivated by both
steric or electronic effects, with methyl alkyl carbonates,
catalyzed by phosphonium salts. The high methylation selectiv-
ity (SDx up to 96%) openly contrasts the behavior claimed for
other methyl carbonates such as DMC and MPC (methyl phenyl
carbonate), whose reactions with amines and Lewis-acidic
catalysts, proceed with the exclusive formation of methyl
carbamates (RNHCO2Me, R ) alkyl, aryl).8,14
(15) (a) Trost, B. Science 1991 254, 1471. (b) Curzons, A.; Constable,
D. J.; Mortimer, D. N.; Cunnigham, V. L. Green Chem. 2001 3, 1-6. (c)
Curzons, A.; Constable, D. J.; Cunnigham, V. L. Green Chem. 2002, 4,
521-527.
(16) Guarr, T.; McGuire, M. E.; McLendon, G. J. Am. Chem. Soc. 1985,
107, 5104-5111.
(17) Kevill, D. N.; Shen, B. W. J. Am. Chem. Soc. 1981, 103, 4515-
4521.
(18) Yoo, S.-D.; Tsuno, Y.; Fujo, M.; Sawada, M.; Yukawa, Y. J. Chem.
Soc., Perkin Trans. 2 1989, 7-13.
(19) (a) Dictionary of Organic Compounds, 5th ed.; Chapman and Hall:
New York, 1982; Vol. 2, p 2063; (b) Vol. 2, p 2068; (c) Vol. 1, p 1055; (d)
Vol. 2, p 2060; (e) Vol. 2, p 2066.
(20) (a) Borkowski, W. L.; Wagner, E. C. J. Org. Chem. 1952, 17, 1128-
1140. (b) Bhattacharyya, S.; Chatterjee, A.; Duttachowdhury, S.-K. J. Chem.
Soc., Perkin Trans. 1 1994, 1-2.
(21) Sim, T. B.; Ahn, J. H.; Yoon, N. M. Synthesis 1996, 324-326.
(22) Katritzky, A. R.; Rachwal, S.; Wu, J. Can. J. Chem. 1989, 68, 456-
463.
The green features of the procedure should also be high-
lighted: although the reaction is quite energy intensive, it is a
catalytic and a solventless process which shows an atom
(23) Bertrand, S.; Hofmann, N.; Humbel, S.; Pete, J. P. J. Org. Chem.
2000, 65, 8690-8703.
J. Org. Chem, Vol. 71, No. 15, 2006 5773