J . Org. Chem. 2001, 66, 677-680
677
Rea ction of P r im a r y Ar om a tic Am in es w ith Alk yl Ca r bon a tes over
Na Y F a u ja site: A Con ven ien t a n d Selective Access to
Mon o-N-a lk yl An ilin es
Maurizio Selva,* Pietro Tundo, and Alvise Perosa
Dipartimento di Scienze Ambientali dell’Universit a` Ca’ Foscari,
Calle Larga S. Marta, 2137-30123 - Venezia, Italy
Received May 1, 2000
At atmospheric pressure and at 130-160 °C, primary aromatic amines (p-XC
NO ) are mono-N-alkylated in a single step, with symmetrical and asymmetrical dialkyl carbonates
ROCOOR′, R ) Me, R′ ) MeO(CH O(CH ; R ) R′ ) Et; R ) R′ ) benzyl; R ) R′ ) allyl; R )
Et, R′ ) MeO(CH O(CH ], in the presence of a commercially available NaY faujasite. No solvents
6 4 2
H NH , X ) H, Cl,
2
[
2
)
2
2 2
)
2
)
2
2 2
)
are required. Mono-N-alkyl anilines are obtained with a very high selectivity (90-97%), in good to
excellent yields (68-94%), on a preparative scale. In the presence of triglyme as a solvent, the
mono-N-alkyl selectivity is independent of concentration and polarity factors. The reaction probably
takes place within the polar zeolite cavities, and through the combined effect of the dual acid-
base properties of the catalyst.
6l
In tr od u ction
oximes,6h aziridines,6i and vinyl derivatives, (ii) metal-
7
a-c
mediated alkylations,
and (iii) nucleophilic aromatic
The direct base-promoted, conventional mono-N-alky-
lation of anilines with toxic and corrosive organic halides
and sulfates1 raises environmental concerns. Besides,
the major synthetic problem is competing bis-N-alkyla-
tion, which leads to mixtures of secondary and tertiary
amines that are very difficult to separate.1 This is
especially true when highly reactive electrophilic com-
pounds (methyl, ethyl, benzyl, and allyl alkylating agents)
are used.3
substitutions.8
a-d
Such a massive experimental effort indicates that a
convenient mono-N-alkylation is an important synthetic
goal. Our approach is based upon the idea of inducing
selectivity by exploiting the steric demand of zeolite
cavities. Selective mono-N-alkylations of primary aro-
matic amines by alkyl halides have been claimed in the
presence of both X- and Y-faujasites.9 Better results
,2
a,b
1
0a-c
have been recently reported by others and by us,
for
Selective mono-N-alkylations of aromatic amines have
been reported by using other alkylating agents such as
the preparation of N-methyl anilines with dimethyl
carbonate (DMC) as the alkylating agent and alkali
cation-exchanged zeolites as the catalysts (Scheme 1).
alcohols,4 alkyl formates, and tellurium derivatives;
a-c
4d
4e
however, reaction conditions are often drastic (high
temperature, sealed vessels, etc.) or reagents are not
readily available.
(
5) (a) Katritzky, A. R.; Drewniak, M.; Aurrecoechea, J . M. J . Chem.
Soc., Perkin Trans. 1 1987, 2539. (b) Carnahan, F. L.; Hurd, C. D. J .
Am. Chem. Soc. 1930, 53, 4587. (c) Nordlander, J . E. et al. Tetrahedron
Lett. 1978, 4987. (d) Lissel, M.; Rohani-Dezfuli, A. R.; Vogt, G. J . Chem.
Res. (S) 1989, 10, 312. (e) Roberts, R. M.; Vogt, P. J . J . Am. Chem.
Soc. 1956, 78, 4778.
(6) (a) Shibata, I.; Suwa, T.; Sugiyama, E.; Baba, A. Synlett 1998,
081. (b) Verardo, G.; Giumanini, A. G.; Strazzolini, P.; Poiana, M.
Synthesis 1993, 121. (c) Pelter, A.; Rosser, R. M. J . Chem. Soc, Perkin
Trans. 1 1984, 717. (d) Feringa, B. L.; J ansen, J . F. G. A. Synthesis
1988, 184. (e) Narasimhan, S.; Madvahan, S.; Balakamur, R.; Swar-
nalakshmi, S. Synth. Commun. 1997, 27, 391. (f) Uchiyama, M. et al.
J . Am. Chem. Soc. 1997, 119, 11425. (g) Krishnamurthy, S. Tetrahe-
dron Lett. 1982, 3315. (h) Sasatani, S.; Miyazaki, T.; Maruoka, K.;
Yamamoto, H. Tetrahedron Lett. 1983, 4711. (i) Almena, J .; Foubelo,
F.; Yus, M. J . Org. Chem. 1994, 59, 3210. (l) Capella, L.; Montevecchi,
P. C.; Navacchia, M. L. J . Org. Chem. 1995, 60, 7424.
(7) (a) Barton, D. H. R.; Doris, E. Tetrahedron Lett. 1996, 3295. (b)
Yoshida, Y.; Tanabe, Y. Synthesis 1997, 533. (c) Bartoli, G.; Marcantoni,
E.; Bosco, M.; Dalpozzo, R. Tetrahedron Lett. 1988, 2251.
(8) (a) Behr, L. C.; Kirby, J . E.; MacDonald, R. N.; Todd, C. W. J .
Am. Chem. Soc. 1946, 68, 1296. (b) Ibata, T.; Isogami, Y.; Toyoda, J .
Bull. Chem. Soc. J pn. 1991, 64, 42. (c) Kotsuki, H.; Kobayashi, S.;
Suenaga, H.; Nishizawa, H. Synthesis 1990, 1145. (d) Katritzky, A.
R.; Laurenzo, K. S. J . Org. Chem. 1988, 53, 3978.
To prevent overalkylation, tedious and expensive mul-
tistep methods have been devised in which partially
protected anilines (amides and thiazoles) were alkylated
5
a-c
5d
with alkyl halides,
dimethyl carbonate, and ortho
1
esters.5
e
Conceptually different strategies to obtain mono-N-
alkyl anilines include (i) reduction of imines,6
a-d
6e-g
amides,
*
To whom correspondence should be addressed. Phone: +39 41 257
687; Fax: +39 41 257 8620.
1) (a) Gibson, M. S. In The Chemistry of the Amino Group; Patai,
S., Ed.; Interscience Pub.: London 1968; Chapter 2, pp 45-62. (b) Hyre,
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Vol. I, p 102.
8
(
(
2) (a) Ono, Y. Pure Appl. Chem. 1996, 68, 367. (b) Selva, M.; Tundo,
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Processes; Anastas, P., Williamson, T., Eds.; Oxford University Press:
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(
3) March, J . In Advanced Organic Chemistry, 4th ed.; Wiley: New
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(4) (a) Watanabe, Y.; Tsuji, Y.; Ige, H.; Ohsugi, Y.; Ohta, T. J . Org.
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1
0.1021/jo0006728 CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/06/2001