A simple method for N-phenoxyethylation of anilines

Article abstract of DOI:10.3390/50300562

We wanted to search for new reaction conditions to prepare the title compounds, to be checked later in novel syntheses of heterocyclic compounds. To the best of our knowledge, there was no report in the literature of any well-established method for the pr

Full text of DOI:10.3390/50300562

562
Molecules 2000, 5
A Simple Method for N-Phenoxyethylation of Anilines
G. P. Romanelli, J. L. Jios, O. Guaymas, R. Piovoso and J. C. Autino
LADECOR, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La
Plata. Calles 47 y 115, B1900AJL La Plata, Argentina
E-mail: jautino@quimica.unlp.edu.ar
Abstract: We wanted to search for new reaction conditions to prepare the title compounds,
to be checked later in novel syntheses of heterocyclic compounds. To the best of our knowl-
edge, there was no report in the literature of any well-established method for the preparation
of N-(2-phenoxyethyl)anilines 1.
The scarce previously reported preparations involved large excesses of some starting materials,
relatively high temperatures and long reaction times [1, 2]. We have recently reported a general proce-
dure for that preparation [3] although at that stage only moderate yields were obtained. We describe
here a better and simpler procedure for achieving not only compounds 1 in good yields, but also for
extending the scope of the reaction to the synthesis of the related bis-N-(2-phenoxy-ethyl)anilines 2. In
order to avoid β-elimination reactions in molecules bearing a phenoxyethyl group, the reaction was
carried out precluding strong acidic or basic media, see Scheme.
R2
O
Br
Y
N
NH2
R2
O
R1
anh. K2CO3 / DMSO
R1
1
2
: Y = H; : Y = -CH2-CH2O-
4
R2
Scheme. N-phenoxyethylation reaction of anilines.
Dependimng on the product desired, 1-bromophenoxyethanes (3) or anilines (4) were used in molar
excess. To prepare mono-N-(2-phenoxyethyl)anilines (1) the reagent 4 was used in excess, yielding 70-
80% (see Table), whereas an excess of 3 lead to 2 with yields ranging in 50-70%.
Reaction conditions involve typically 90°C, DMSO as solvent and anhydrous K2CO3 as the base.
Yields are substantially improved as compared with those already obtained using triethylamine [3].
New compounds 2b and 2c gave satisfactory analytical and spectroscopic data.

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Molecules 2000, 5
Table. Selected examples of N-(2-phenoxyethyl)anilines 1 and 2.
Compound
R1
H
R2
H
% Yield
75
1a
1b
1c
1d
1e
2a
2b
2c
H
OMe
NO2
H
72
H
71
OMe
NO2
H
79
H
58
H
55
H
Cl
59
Cl
H
63
References and Notes
1. Oki, M.; Mutai, K. Intramolecular N-H...O hydrogen bonding in N-(ω-phenoxyalkyl)anilines.
Spectrochim. Acta 1969, A25, 1941.
2. Mutai, K.; Tukada, H.; Nakagaki, R. Bifunctional Reactivity of the Nitrophenoxyl Group in In-
tramolecular Photoreactions. J. Org. Chem. 1991, 56, 4896.
3. Autino, J. C.; Bruzzone, L.; Romanelli, G. P.; Jios, J. L.; Ancinas, H. A. Substituted N-
phenoxyethylanilines: preparation and acid-base properties evaluation by fluorescence spec-
trometry. Anales de Química, Intern. Ed. 1998, 94, 292.