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Table 3 N-alkylation of aromatic amines with various alcohols under solvent-
free conditionsa
Yieldb
(%)
Yieldb
(%)
Entry T
Product
Entry T
Product
Scheme 4 N-heterocyclization of amino alcohols.
1
2
3
50 1C/r.t.
95/93
90/92
93/63
6
7
8
9
50 1C/r.t.
90/92
92/91
93/90
96/93
In conclusion, we have developed the iridium complex 3, which
bears a bidentate NHC–phosphine ligand and is an efficient
catalyst for the N-alkylation of anilines with alcohols. A variety of
aromatic amines were converted to the corresponding secondary
amines with a range of alcohols in good to excellent yields.
Cyclization of amino alcohols was also successful, producing indole
and 1,2,3,4-tetrahydroquinoline. For the first time, this type of
transformation has been carried out at room temperature.
50 1C/r.t.
50 1C/r.t.
50 1C/r.t.
50 1C/r.t.
50 1C/r.t.
4
5
a
50 1C/r.t.
50 1C/r.t.
94/91
93/85
Reaction conditions: 1.0 mmol aniline, 1.1 mmol alcohol, 0.5 mmol
KOtBu; 0.5 mol% catalyst, 50 1C, 24 h or 1.0 mol% catalyst, r.t., 48 h.
b
Isolated yield.
Notes and references
yields under solvent-free conditions (Table 3). Notably, the reaction of
aniline with para-CF3-substituted benzyl alcohol was very clean under
neat conditions and provided the corresponding mono-
alkylated product in an excellent isolated yield of 93% (entry 5,
50 1C). We even carried out some reactions under solvent-free
conditions at room temperature with 1.0 mol% of the catalyst for
48 h. A low yield in the reaction of 4-bromoaniline and benzyl alcohol
was a consequence of incomplete conversion (entry 3, r.t.). The
solubility of solid 4-bromoaniline was poor under these mild condi-
tions, causing inefficient stirring in the resulting heterogeneous
reaction. Interestingly, when aliphatic alcohols were employed as
alkylating reagents at 50 1C or at room temperature under solvent-
free conditions, a higher catalyst loading than that used for benzyl
alcohol was not needed because the high concentration of reactants
led to more favorable kinetics than in solution (entries 7–9).23
There are only a few reports on the preparation of N,N0-dialkyl-
ated diamines using this method, and long reaction time or high
temperature was required for each of them.10b,12a We applied our
approach to the alkylation of dapsone 5 and 1,3-benzenediamine 7
(Scheme 3). Excellent isolated yields were achieved. No mono-N-
alkylated amines were observed under the reaction conditions used.
Finally, intramolecular alkylation was attempted. With
2-(2-aminophenyl)ethanol 9 as the substrate, indoline would
not be the expected product; rather, the isomerization of the
intermediate 11 to indole 12 should be driven by aromatization
(Scheme 4, left). When complex 3 was applied to N-hetero-
cyclization of 3-(2-aminophenyl)propanol 13, the intermediate
3,4-dihydroquinoline 15 could not be dehydrogenated by
the present catalytic system, thus 1,2,3,4-tetrahydroquinoline
16 was obtained as the only product (Scheme 4, right).
These observations were consistent with the previous study of
N-heterocyclization of amino alcohols by [Cp*IrCl2]2.15
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Scheme 3 N,N0-Dialkylation of dapsone and 1,3-benzenediamine.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 6131--6133 6133