Base-mediated rearrangement of free aromatic hydroxamic acids (ArCO-NHOH) to anilines

Article abstract of DOI:10.1039/b822806j

Without using activating agents, a variety of free aromatic hydroxamic acids could be rearranged to aromatic amines in the presence of base alone. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b822806j

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Base-mediated rearrangement of free aromatic hydroxamic acids
ArCO–NHOH) to anilinesw
(
a
a
a
b
a
Yujiro Hoshino,* Moriaki Okuno, Eri Kawamura, Kiyoshi Honda and Seiichi Inoue
Received (in Cambridge, UK) 18th December 2008, Accepted 11th February 2009
First published as an Advance Article on the web 9th March 2009
DOI: 10.1039/b822806j
Without using activating agents, a variety of free aromatic
hydroxamic acids could be rearranged to aromatic amines in
the presence of base alone.
activation, the direct synthesis of amines from free hydroxamic
acids is more attractive.
The Lossen rearrangement of hydroxamic acid derivatives,
e.g., O-acyl hydroxamic acids, is a useful method for the
preparation of amines from parent carboxylic acids under
ð1Þ
1
mild reaction conditions. It is well documented in the
2
3
literature and textbooks that the activation of the oxygen
atom of hydroxamic acids is essential for the rearrangement to
take place because hydroxide is a much poorer leaving group.
Thus, Lossen rearrangement is usually carried out by using
prepared O-activated hydroxamic acid derivatives or by in situ
activation of free hydroxamic acids with an activating agent
In order to assess the influence of base and solvent, we
examined the base-mediated rearrangement of p-methylbenzo-
hydroxamic acid (1a) as a standard substrate. As shown in
Table 1, several inorganic and organic bases could induce the
rearrangement, and better results were obtained by using
4
5
such as polyphosphoric acid, carbodiimide, azodicarboxylate
6
and triphenylphosphine (Mitsunobu condition), sulfonyl
K
2
CO
basicity of metal carbonates led to increase of reaction yields
entries 1–4). Among organic bases examined, a relatively
3
, Cs
2
CO
3
and K
3
PO
4
(entries 3–5).z Increasing the
7
8
chloride, sulfur trioxide triethylamine complex, or nitrile.
9
(
We were therefore quite surprised to observe in the course of
our investigation to explore an alternative synthetic method
for N-arylhydroxamic acids via copper-catalyzed N-arylation
stronger base, DBU, gave a satisfactory result (entry 9). It is
likely that pK values of conjugate acid of the bases would be
a
1
0
required to be 49 in order to effectively promote the reaction.
Although Cs CO and K PO gave similar yields to K CO ,
with aryl iodide that free benzohydroxamic acid, without
addition of external activating agent, could be converted to
aniline in moderate yield, which means occurrence of C to N
migration of the aryl group (eqn (1)). This amazing result
prompted us to investigate the literature on the rearrangement
of free hydroxamic acids without activating agent. Two groups
2
3
3
4
2
3
the latter was chosen for further study since it is much cheaper.
Table 1 The base-mediated rearrangement of p-methylbenzo-
hydroxamic acid (1a)
0
reported the production of N,N -diphenylurea derivatives
1
1,12
instead of anilines.
Spontaneous Lossen rearrangement
of (phosphonoformyl)hydroxamate to phosphoramidate was
1
3
also reported. As a notable exception, Kobayashi et al.
reported a small production of perfluoroaniline as a by-product
in the treatment of electron-deficient perfluorobenzohydroxamic
a
Yield (%)
Entry
Base
Solvent
Recovery (%)
1
4
acid with K CO in boiling water. As far as we know, it is the
2
1
2
3
4
5
6
7
8
9
10
Li CO
2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
NMP
MeCN
12
81
92
93
71
14
—
—
—
89
97
97
—
—
7
73
86
95
84
80
—
90
3
3
Na
CO
CO
PO
HPO
2
CO
3
only example for the base-mediated rearrangement of free
hydroxamic acid to aniline under standard solution-phase
K
2
3
Cs
2
3
1
5
conditions and, unfortunately, this reaction has not been
thoroughly explored to date. Herein, we wish to report the
base-mediated rearrangement of a variety of aromatic hydroxamic
acids to aromatic amines without activating agents. Because of
advantage associated with no use of additional reagent for
K
K
3
4
96
2
4
Trace
Trace
Trace
97
98
90
21
10
—
12
Imidazole
Et
DBU
3
N
K CO
2
3
3
3
3
3
3
3
3
1
1
1
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
CO
CO
CO
CO
CO
CO
CO
b
a
13
MeOH
THF
Graduate School of Environment and Information Sciences,
b
1
1
1
17
1
4
5
6
Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku,
Yokohama, 240-8501, Japan. E-mail: yhoshino@ynu.ac.jp;
Fax: +81-45-339-4434; Tel: +81-45-339-4434
Graduate School of Engineering, Yokohama National University,
79-5 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan
Toluene
n-BuOH
DMSO
DMF
11
91
0
c
b
8
None
w Electronic supplementary information (ESI) available: Experimental
procedures, spectroscopic data, and copies of H and C NMR
spectra. See DOI: 10.1039/b822806j
a
b
Isolated yield based on 1a. The reactions were carried out at
1
13
c
reflux. The reaction was carried out at 70 1C for 6 h.
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The influence of solvent was next examined (Table 1,
entries 10–16). According to the solvent used, the yield of
amine is dramatically varied. Polar aprotic solvents gave the
best results (90–98%, entries 10 and 11), whereas medium- or
non-polar aprotic or polar protic solvents afforded low yields
Table 2 The base-mediated rearrangement of a variety of free
aromatic hydroxamic acids 1
(
0–21%, entries 12–16). It is noted that increasing the polarity
1
of solvents led to a significant improvement in yield.
6
Lowering the reaction temperature to 70 1C could also afford
a good yield (91%) but the reaction needed a much longer time
(
6 h) to be completed (entry 17). It should be noteworthy that
the rearrangement can proceed in good yields even though less
than 1 equiv. of K CO is used. For instance, with 0.05 equiv.
of K CO , the corresponding aniline was obtained in 91%
2
3
2
3
yield (eqn (2)).w Although it is not necessary to conduct the
process under extremely anhydrous condition (the reaction
was performed under air using distilled solvent), a decrease of
the yield is observed when water (3 vol% in solvent, 5.6 equiv.
to substrate) is added to the reaction mixture in the presence of
substoichiometric base (1 h, 63% yield) (eqn (2)). Finally, we
confirmed that in the absence of a base no aniline was detected
1
7
(
entry 18).
ð2Þ
In order to study the scope of this reaction, a series
of experiments were carried out using various aromatic
hydroxamic acids (Table 2). To our delight, all substrates
examined were transformed to the corresponding amines in
high yields. Good yields were obtained with the parent
benzohydroxamic acid 1b (entry 1). The rearrangement of
electron-rich hydroxamic acids, regardless of o-, m- and
p-substituent pattern, proceeded smoothly (entries 2–4, 9–10,
and Table 1). Similarly, electron-deficient hydroxamic acids
1
f–h were effectively converted to the synthetically important
halogenated anilines, although a slight decrease of reaction
rate was observed by TLC analysis. In this case, a small
amount of the parent carboxylic acids was isolated as a
by-product (entries 5–8). For the more electron-deficient
substrate p-nitrobenzohydroxamic acid (1i), a longer reaction
time was required to consume the starting material, but the
good yield was maintained. This order of reactivity is
consistent with the usual trend for the Lossen rearrangement
a
The reaction was performed for 9 h in 4 mL of DMSO in order to
b
dissolve the reaction mixture. The reaction time is 5 min.
substitution with nitrogen electrophiles, which frequently
2
suffer from the lack of regioselectivity of the reaction. In
1
1
8
of O-acyl hydroxamic acids, but it is noted that the high
addition, compared to reduction of halogenated aromatic
2
nitro compounds to haloanilines, this method can give them
in good to excellent yields with high chemoselectivities.
2
yields are retained even when electron-deficient hydroxamic
1
9
acids are used. Interestingly, the rearrangement of sterically
demanding, highly electron-rich 2,6-dimethoxybenzohydroxamic
acid (1j) proceeded rapidly (within only 5 min) with intense
generation of foam just before 90 1C. A useful synthetic
intermediate 2,3-dimethoxyaniline (2k), used for synthesis of
A
possible reaction pathway of the base-mediated
rearrangement of free hydroxamic acids to amines is shown
in Scheme 1. We consider that a very small amount of
isocyanate is acting in a chain reaction as a reactive
intermediate, which is initially installed by self-acylation and
rearrangement in the presence of base (Scheme 1(a)):
O-acylation of hydroxamic acid by another one occurs in a
2
0
some alkaloids, is also obtained in high yield (entry 10). It is
important that in the all cases the regioisomer of the product
was not detected at all. This high regiospecificity appeared
to be a great merit compared to the conventional methods
for preparing the amines through electrophilic aromatic
2
3
small quantity to give O-acyl hydroxamate A, which is
rearranged to isocyanate B along with release of carboxylate.
2
282 | Chem. Commun., 2009, 2281–2283
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1
(a) W. Lossen, Liebigs Ann. Chem., 1872, 161, 347; (b) W. Lossen,
Liebigs Ann. Chem., 1874, 175, 271; (c) W. Lossen, Liebigs Ann.
Chem., 1874, 175, 313.
2
3
(a) L. Bauer and O. Exner, Angew. Chem., Int. Ed. Engl., 1974, 13,
3
For an example, see: L. Kurti and B. Czako, Strategic Applications
76; (b) H. L. Yale, Chem. Rev., 1943, 33, 209.
´
¨
of Named Reactions in Organic Synthesis, Elsevier Academic Press,
Burlington, MA, 2005, pp. 266–267.
4
(a) H. R. Snyder, C. T. Elston and D. B. Kellom, J. Am. Chem.
Soc., 1953, 75, 2014; (b) G. B. Bachman and J. E. Goldmacher,
J. Org. Chem., 1964, 29, 2576.
5
6
D. G. Hoare, A. Olson and D. E. Koshland, Jr, J. Am. Chem. Soc.,
1
968, 90, 1638.
S. Bittner, S. Grinberg and I. Kartoon, Tetrahedron Lett., 1974, 15,
965.
1
7
8
D. Samuel and B. L. Silver, J. Am. Chem. Soc., 1963, 85, 1197.
F. A. Daniher, J. Org. Chem., 1969, 34, 2908.
Scheme
1
A
possible reaction pathway of the base-mediated
9 (a) T. Obayashi (Fuji Photo Film Co.), Jpn. Kokai Tokkyo Koho,
JP 05 246 961 [93 246 961], 1993US Pat., 5 354 891, October 11,
rearrangement of free hydroxamic acids to amines.
1
994; (b) A. Okawa and T. Obayashi (Fuji Photo Film Co.), Jpn.
Kokai Tokkyo Koho, JP 08 119 908 [96 119 908], 1996.
0 Recently, copper-catalyzed N-arylation of protected hydroxyl-
amines with aryl iodides was reported, see: K. L. Jones,
A. Porzelle, A. Hall, M. D. Woodrow and N. C. O. Tomkinson,
Org. Lett., 2008, 10, 797.
The isocyanate B is rapidly attacked by hydroxamic acid to
generate O-carbamoyl hydroxamate C, the rearrangement of
1
2
4
which gives aniline 2 and regenerates isocyanate B. This
newly generated isocyanate reacts with hydroxamic acid (1) in
the same manner and, thus, this chain reaction cycle is
completed (Scheme 1(b)). According to this scheme, it is
rationalized that the reaction can be conducted using a
catalytic amount of base and the addition of a small amount
of water reduces the yield of aniline due to the trapping of a
reactive intermediate isocyanate. Finally, in order to test the
possibility of production of aniline via hydrolysis of urea
1
1 (a) J. Podlaha, I. Cı
O. Exner, J. Chem. Res. (S), 1998, 520; (b) J. Podlaha,
I. Cısarova, L. Soukupova, J. Schraml and O. Exner, J. Chem.
Res. (M), 1998, 2079.
sarova, L. Soukupova, J. Schraml and
´ ˇ ´ ´
´
ˇ
´
´
1
1
2 G. Caronna and F. Maggio, Gazz. Chim. Ital., 1953, 83, 527.
3 C. J. Salomon and E. Breuer, J. Org. Chem., 1997, 62, 3858.
14 Y. Inukai, Y. Oono, T. Sonoda and H. Kobayashi, Bull. Chem.
Soc. Jpn., 1981, 54, 3447.
1
5 A study on the collisional activation mass spectra of deprotonated
hydroxamic acids in the gas phase was reported, see:
1
1,12
0
(
vide supra),
N,N -bis(4-methylphenyl)urea was subjected
(a) G. W. Adamas, J. H. Bowie and R. N. Hayes, J. Chem. Soc.,
to the identical conditions, but no reaction occurred.
Perkin Trans. 2, 1991, 689; (b) some examples of the thermal
rearrangement of hydroxamates in autoclave above 150 1C were seen
in a patent, see: J. Nishikido, Y. Fukuoka and N. Tamura (Asahi
Kasei Kogyo Kabushiki Kaisha), US Pat., 4 279 836, July 21, 1981.
In conclusion, we have demonstrated a base-mediated
rearrangement of a variety of aromatic hydroxamic acids to
amines without using activating agents. This reaction can be
effectively performed by various inorganic and organic bases
16 It is interesting to note that the order of the p* scale of solvents
except for low boiling solvents (MeOH and THF) is almost parallel
to that of yields of aniline, see ESIw.
(
stoichiometric or catalytic amount) in polar aprotic solvents.
1
1
1
2
7 In the case that the reaction was conducted without a base for a
In addition to its simplicity and efficiency, this method
produces aromatic amines in excellent yields in short reaction
times. Further work is in progress in this laboratory to apply
this reaction to aliphatic hydroxamic acids and to study the
mechanism of this base-mediated rearrangement of free
hydroxamic acids.
long time (5 days), a small amount (o0.05 equiv.) of carboxylic
1
acid and urea was detected by H NMR analysis.
8 (a) R. D. Bright and C. R. Hauser, J. Am. Chem. Soc., 1939, 61,
6
1
18; (b) W. B. Renfrow, Jr and C. R. Hauser, J. Am. Chem. Soc.,
937, 59, 2308.
9 (a) R. Anilkumar, S. Chandrasekhar and M. Sridhar, Tetrahedron
Lett., 2000, 41, 5291; (b) R. G. Wallace, J. M. Barker and
M. L. Wood, Synthesis, 1990, 1143. see also refs. 4a, 6, 18a, and b.
0 (a) E. L. Larghi, B. V. Obrist and T. S. Kaufman, Tetrahedron, 2008,
6
2
4, 5236; (b) K. S. Feldman and A. Coca, Tetrahedron Lett., 2008, 49,
136; (c) J. M. Mejıa-Oneto and A. Padwa, Org. Lett., 2006, 8, 3275.
´
Notes and references
z General procedure for the base-mediated rearrangement of free
21 M. B. Smith and J. March, March’s Advanced Organic Chemistry:
Reactions, Mechanisms, and Structure, John Wiley & Sons,
New York, 2007, pp. 665–677.
hydroxamic acids to amines: A mixture of p-methylbenzohydroxamic
acid 1 (0.363 g, 2.4 mmol), K
2 3
CO (0.332 g, 2.4 mmol) and DMSO
(
2 mL) was heated to 90 1C and stirred for 2 h. The mixture was cooled
22 (a) G. W. Kabalka and R. S. Varma, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford,
1991, vol. 8, p. 363; (b) M. R. Pitts, J. R. Harrison and
C. J. Moody, J. Chem. Soc., Perkin Trans. 1, 2001, 955.
23 M. Thomas, J.-P. Gesson and S. Papot, J. Org. Chem., 2007, 72, 4262.
24 (a) J. Pihuleac and L. Bauer, Synthesis, 1989, 61; (b) K. Nagarajan,
S. Rajappa and V. S. Iyer, Tetrahedron, 1967, 23, 1049.
to rt, then treated with 2 M HCl (ca. 3 mL). After the mixture became
a clear solution, 2 M NaOH (ca. 3 mL) was added and extracted with
Et
Na
was purified by silica gel column chromatography (hexane–Et O, 1 : 1)
2
to yield the pure p-methylaniline (0.253 g, 98%).
2
O (15 mL x 3). The combined layers were dried over anhydrous
SO , filtered and evaporated under reduced pressure. The residue
2
4
This journal is ꢀc The Royal Society of Chemistry 2009
Chem. Commun., 2009, 2281–2283 | 2283