A new method for N-N bond cleavage of N,N-disubstituted hydrazines to secondary amines and direct ortho amination of naphthol and its analogues

Article abstract of DOI:10.1021/ja711153b

An unexpected reaction of N,N-disubstituted hydrazine with naphthol and its analogues under simply thermal conditions has been disclosed. 2-Naphthol reacted with various N,N-disubstituted hydrazines under argon to afford 1-amino-2-naphthol and the corresponding secondary amines in excellent yields. Ortho amination of 2-naphthols, hydroxyquinoline, and naphthalenamine occurred when they reacted with N-methyl-N-phenylhydrazine. Copyright

Full text of DOI:10.1021/ja711153b

Published on Web 04/12/2008
A New Method for N-N Bond Cleavage of N,N-Disubstituted
Hydrazines to Secondary Amines and Direct Ortho Amination
of Naphthol and Its Analogues
Qiang Tang, Chao Zhang, and Meiming Luo*
Key Laboratory of Green Chemistry and Technology of Ministry of Education at Sichuan
UniVersity, College of Chemistry, Sichuan UniVersity, Chengdu 610064, PR China
Received December 16, 2007; E-mail: luomm@scu.edu.cn
Scheme 1a
N-N bond cleavage in hydrazines occupies a significant place
in chemistry for the synthesis of amines1 which are important
pharmacophores in numerous biologically active compounds and
have been greatly touted in the area of drug discovery.2
Developing efficient and general preparative methods for
secondary amines from N,N-disubstituted hydrazines is of
promising interest. On the other hand, the ortho-aminated
derivatives of naphthol and its analogues have a broad range
of applications in preparation of dyes,3 pharmaceuticals,4 and
so on. Traditionally, ortho-aminated naphthol and its analogues
are prepared by nitration and subsequent reduction,4b,d,5 reduc-
tion of azo-compounds,6 which often suffer from harsh condi-
tions and limited generality. Direct ortho amination, which is
superior to traditional methods at least with respect to synthetic
steps, is quite rare. A thorough search of the literature revealed
a single report of R-amination reaction of 2-naphthol with N,N-
dimethylhydrazine under radical reaction conditions: sodium
methoxide and oxygen atmosphere as well as irradiation with a
tungsten lamp.7 It was especially pointed out that no aminated
product could be detected under argon. The substrates were
limited to 2-naphthol, N,N-dimethyl-, and N,N-diethylhydrazine.7
This Communication describes an unexpected reaction of
N,N-disubstituted hydrazines with naphthol and its analogues
under simply thermal conditions that leads to a general and
efficient method for the N-N bond cleavage of N,N-disubsti-
tuted hydrazines and direct ortho amination of naphthol and its
analogues.
a Reaction conditions: 1:1 substrate molar ratio, 80 °C, argon atmosphere.
Table 1. Reaction Results of 2-Naphthol with N,N-Disubstitued
Hydrazinesa
The reaction of naphthol with hydrazines usually results in
the substitution of the phenolic hydroxyl group of naphthol by
hydrazine residue, and then followed by benzidine rearrange-
ment to produce the corresponding 2,2′-diamino-1,1′-biaryls or
carbazoles in the case of arylhydrazines.8 To our surprise,
however, when we heated a mixture of 2-naphthol with
N-methyl-N-phenylhydrazine at 80 °C under argon atmosphere,
we obtained the unexpected R-aminated product 1-amino-2-
naphthol and N-methylaniline (Scheme 1).
A preliminary study was performed to determine the substrate
scope of this reaction. To our delight, not only N-alkyl-N-
arylhydrazines (Table 1, entries 1-6), but other types of N,N-
disubstituted hydrazines, N,N-diarylhydrazine (Table 1, entry
7), N,N-dialkylhydrazines (Table 1, entries 8 and 9) also reacted
smoothly with 2-naphthol under argon to afford 1-amino-2-
naphthol and the corresponding secondary amines in good to
excellent yields. The reaction was typically performed at a
temperature slightly higher than that of where the reactants
mixture melted.9 However, in the case of N-benzyl-N-phenyl-
hydrazine and N,N-diphenylhydrazine, the reaction did not occur
at a temperature lower than 100 °C (Table 1, entries 3 and 7).
a Reaction conditions: 1:1 molar ratio of 2-naphthol to hydrazine,
argon atmosphere. b Isolated yields. c Reaction run using 2 equiv of
hydrazine. d Reaction was carried out in methanol at 20 °C. e The yield
was not measured.
N,N-Dimethylhydrazine reacted cleanly under argon and thermal
conditions to afford 1-amino-2-naphthol in 91% yield (Table
1, entry 8). The yield of gaseous dimethylamine was not
determined. The reaction of N,N-diisobutylhydrazine was more
complex judged from TLC, thus offered moderate yields of the
desired products (Table 1, entry 9). N-Acyl-N-arylhydrazines
such as N-acetyl-N-phenylhydrazine and N-benzoyl-N-phenyl-
hydrazine were also examined, but we did not detect any
R-aminated product even at a higher temperature.
9
5840 J. AM. CHEM. SOC. 2008, 130, 5840–5841
10.1021/ja711153b CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Reaction Results of N-Methyl-N-phenylhydrazine with
not give the ortho-aminated product 2-amino-1-naphthol, 8-hy-
droxyquinoline produced 7-amino-8-hydroxyquinoline in about
30% yield (Table 2, entry 9). 2-Naphthalenamine could also be
ortho aminated by this method giving naphthalene-1,2-diamine
in 40% yield (Table 2, entry 10). In the case of 1-naphthale-
namine, only 10% of the ortho-aminated product was attained
(Table 2, entry 11). Monocyclic phenols and arylamines, such
as phenol, 4-methylphenol, 4-methoxyphenol, 4-nitrophenol,
aniline, and N-methylaniline did not undergo this reaction.
In summary, an unexpected reaction of N,N-disubstituted
hydrazine with naphthol and its analogues under simply thermal
conditions has been disclosed. This finding provides a new
general approach to the cleavage of N-N bond of N,N-
disubstituted hydrazines, which can be used for the synthesis
of secondary amines. The direct ortho amination of naphthol
and its analogues, which is advantageous over traditional
synthesis, may find its wide application in preparation of many
valuable organic compounds. Further work will focus on the
reaction mechanism, the reactions of structurally more complex
hydroxyl- and amino-substituted arenes, as well as the utilization
of this reaction in the syntheses of complex molecules.
Analogues of 2-Naphthola
Acknowledgment. We thank the National Natural Science
Foundation of China for financial support. We are also grateful
to the Analytical & Testing Center of Sichuan University for
supports in NMR and MS analyses.
Supporting Information Available: Experimental procedures
and spectroscopic characterization of the products. This material
is available free of charge via the Internet at http://pubs.acs.org.
References
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To further evaluate the scope of this reaction, a variety of
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lenediol. This may be attributed to the steric hindrance rising
from the amino group that is already situated at C-1. The same
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with N-methyl-N-phenylhydrazine under similar conditions. The
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