Beckmann rearrangement of oximes catalyzed by cyanuric chloride in ionic liquids

Article abstract of DOI:10.1055/s-2008-1042804

The Beckmann rearrangement of a variety of ketoximes has been carried out in imidazolium-based ionic liquids in the presence of catalytic amounts of 2,4,6-trichloro[1,3,5]triazine. This mild and 'green' procedure is highly regioselective affording the corresponding N-substituted amides in very good to quantitative yields. The ionic liquids were easily recovered and recycled several times. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1042804

908
LETTER
Beckmann Rearrangement of Oximes Catalyzed by Cyanuric Chloride in
Ionic Liquids
B
eckmannRearr
e
ngement
o
c
f
O
ximes ilia Betti,a Dario Landini,*a Angelamaria Maia,*b Maurizio Pasia
a
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy
Fax +39(02)50314159; E-mail: dario.landini@unimi.it
b
Istituto CNR-ISTM, Via Golgi19, 20133 Milano, Italy
E-mail: angelamaria.maia@istm.cnr.it
Received 14 December 2007
Cl
Abstract: The Beckmann rearrangement of a variety of ketoximes
has been carried out in imidazolium-based ionic liquids in the pres-
ence of catalytic amounts of 2,4,6-trichloro[1,3,5]triazine. This
mild and ‘green’ procedure is highly regioselective affording the
corresponding N-substituted amides in very good to quantitative
yields. The ionic liquids were easily recovered and recycled several
times.
N
N
NOH
R2
O
Cl
N
Cl
R1
R2
NHR1
IL
Scheme 1
Key words: oximes, amides, Beckmann rearrangement, ionic liq-
uids, cyanuric chloride catalysis
Here we report that the Beckmann rearrangement of a rep-
resentative series of oximes (Table 1, entries 1–7) can be
successfully carried out in imidazolium-based ionic liq-
uids in the presence of catalytic amounts of TCT, at 60 °C
or 130 °C (Scheme 1).9
The Beckmann rearrangement represents a widely used
method in organic chemistry to obtain amides from the
corresponding ketoximes.1 The reaction requires in gener-
al high temperatures (about 130 °C) and excess or
stoichiometric quantities of strongly acidic and dehydrat-
ing media, such as concentrated sulfuric acid, phospho-
rous pentachloride in diethyl ether, or hydrogen chloride
in a mixture of acetic acid and acetic anhydride.1 As a con-
sequence, this reaction can lead to a large amount of
byproducts and, most importantly, cannot be applied to
sensitive substrates. Among the various possibilities for
realizing these reactions under milder conditions,2 the use
of room-temperature ionic liquids (IL) instead of the more
common polar media has been reported.3–5 Ionic liquids
have negligible vapor pressure and excellent thermal sta-
bility that combined with easy preparation, recycling, and
good solvating ability of a wide range of substrates and
catalysts, makes them viable ecosustainable solvents for a
number of stoichiometric and catalytic processes.6 This
class of novel solvents is attracting increasing popularity
as a potential ‘green’ alternative to conventional volatile
organic media (DMF, MeCN, etc.) that should be utilized
only in limited quantities due to their significant environ-
mental impact.6
All reactions are fully regioselective affording only one of
the two possible N-substituted amides in very good to
quantitative yields.
Electron-donating substituents (OH, OMe) on the aromat-
ic ring were found to reduce the reaction time (entries 3
and 6) in comparison with the unsubstituted oxime (entry
2). In contrast, the rearrangement reaction was slower
with the electron-withdrawing groups (NO2 and Cl, en-
tries 4 and 5).
The results obtained with the cyclohexanone oxime are of
particular interest due to the importance of e-caprolactam
as starting material for the large scale manufacture of 6-
nylon.10 The conversion of the oxime to e-caprolactam
proceeded quantitatively within two hours at 60 °C in the
presence of 20 mol% of TCT (82% with 2 mol% of cata-
lyst after 14 h, entry 7).
It is worth noting that, contrary to previous reports by oth-
er authors,8 under our conditions no Lewis acids or Brøn-
sted acids were necessary as cocatalysts to further
increase the catalytic activity of TCT. Our data seem to in-
dicate once again that not only the most acidic H2 but all
the hydrogens of the imidazolium cation are involved in
the reaction.11,12 As shown in Table 2, in fact, when the re-
arrangement of the benzophenone oxime was performed
in the methylated ionic liquid 1-hexyl-2,3-dimethylimida-
zolium perchlorate, [hmmim][ClO4], in which the hydro-
gen in the C2 position is substituted by a methyl group
(entry 4), the reaction was only slightly slower than that in
1-hexyl-3-methylimidazolium perchlorate, [hmim][ClO4]
(3 h instead of 2 h). Commercial imidazolium ionic liq-
uids such as [hmim][PF6], [hmim][BF4], and 1-butyl-3-
methylimidazolium bromide, [bmim][Br], proved to be as
Recently, 2,4,6-trichloro[1,3,5]triazine (cyanuric chlo-
ride, TCT) has been used in stoichiometric7 or catalytic8
amounts for the rearrangement of ketoximes into the cor-
responding N-substituted amides in polar solvents (DMF,
MeCN, MeNO2).
SYNLETT 2008, No. 6, pp 0908–0910
Advanced online publication: 11.03.2008
DOI: 10.1055/s-2008-1042804; Art ID: G37307ST
© Georg Thieme Verlag Stuttgart · New York
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LETTER
Beckmann Rearrangement of Oximes
909
Table 1 TCT-Catalyzed Beckmann Rearrangement of Oximes in [hmim][ClO4] at 60 °C or 130 °Ca
Entry
1
Oxime
Amide
Catalyst (%)
2
Temp (°C) Time (h)
Yield (%)b
99 (83)c,d
O
NOH
Ph
NOH
60
60
2
2
Ph
Ph
O
N
Ph
Ph
H
2
3
2
2
93
88
Ph
N
H
NOH
NOH
OH
NO2
Cl
O
O
60
1.5
8
N
H
HO
4
5
6
7
2
2
2
130
60
90
N
H
O2N
NOH
O
O
5
90
N
H
Cl
OMe NOH
60
1.75
99 (90)c
N
H
OMe
O
NOH
2
20
60
60
14
2
82
99 (67)c
NH
a A solution of oxime (0.3–1 mmol) and TCT (2–20 mol%) in the IL (1 mL).
b Isolated yield by chromatography of the IL solution.
c Isolated yield by chromatography of the crude extracted with MTBE.
d Same yield was obtained after 3 h in MeCN.
much suitable as [hmim][ClO4] (comparable yields and with protracted dehydration procedures, the reaction time
times, entries 5–7 of Table 2). In particular, with was almost the same (1.45 h instead of 2 h).
[bmim][Br] the workup was particularly simple. Since
Interestingly, the ionic liquid [hmim][ClO4] was easily re-
this IL is miscible with water it was easily separated from
covered and reused.9 For example, the benzophenone
the reaction system by water extraction and so the pure
oxime (1 mmol; Table 2, entry 1) rearranged to the corre-
amide could be quantitatively recovered without further
sponding amide in similar yield and purity of the first run
purification (chromatography).
over three cycles (87%, 91%, 90%, respectively).
Ionic liquids are known to retain a significant quantity of
Finally, the reaction of the benzophenone oxime was also
water after a standard workup (2000 100 ppm H2O).
performed in acetonitrile8 for the sake of comparison with
This residual water can play a leading role in determining
the molecular solvents. In this medium, as shown in foot-
the product distribution, the formation of unwanted
note d of Table 1, the amide formation is slightly slower
byproducts and, most importantly, the reaction rate.13 We
than in the IL (3 h instead of 2 h).
have investigated the effect of the water present in the re-
In conclusion, this paper presents a mild and ‘green’ pro-
action medium on the rearrangement of the benzophenone
cedure for obtaining amides from the corresponding ket-
oxime in the range of 2000–6000 ppm H2O. The results,
oximes in imidazolium-based ionic liquids under catalytic
presented in Table 2 (entries 1–3), show that by increasing
conditions. Cyanuric chloride revealed a cheap and effec-
the water content, from 2100 to about 3300 ppm H2O, the
tive catalyst and no additional cocatalysts were necessary
amide formation required more time (3.25 h instead of 2
to promote the rearrangement. The Beckman-type reac-
h). By further increasing the IL hydration (about 5800
tions are fully regioselective, affording the products in
ppm H2O) the rearrangement became remarkably slower
very good to quantitative yields. In addition, the ionic liq-
and only 63% of amide together with 32% of starting
uid was easily recovered and recycled several times.14
oxime were recovered after 45 hours. Alternatively, by re-
ducing the water content from 2100 to about 700 ppm
Synlett 2008, No. 6, 908–910 © Thieme Stuttgart · New York

910
C. Betti et al.
LETTER
(5) (a) Gui, J.; Deng, Y.; Hu, Z.; Sun, Z. Tetrahedron Lett. 2004,
45, 2682. (b) Guo, S.; Du, Z.; Zhang, S.; Li, D.; Li, Z.; Deng,
Y. Green Chem. 2006, 8, 296; and references therein.
(6) (a) Ionic Liquids IIIB: Fundamentals, Progress, Challenges
and Opportunities – Transformations and Processes;
Rogers, R. D.; Seddon, K. R., Eds.; American Chemical
Society: Washington DC, 2005. (b) Ionic Liquids IIIA:
Fundamentals, Progress, Challenges and Opportunities –
Properties and Structure; Rogers, R. D.; Seddon, K. R.,
Eds.; American Chemical Society: Washington DC, 2005.
(c) Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis;
VCH: Weinheim, 2003. (d) Chowdhury, S.; Mohan, R. S.;
Scott, J. L. Tetrahedron 2007, 63, 2363.
Table 2 Effect of the Ionic-Liquid and Water in the TCT-Catalyzed
Beckmann Rearrangement of Benzophenone Oxime at 60 °Ca
Entry Ionic liquid
H2O
Catalyst Time (h) Yield
(%)
(ppm)b
(%)c
1
[hmim][ClO4]
2100
2
2
99 (83)d
(87)d
0.75e
2
3
4
5
6
7
[hmim][ClO4]
[hmim][ClO4]
3300
5800
2
3.25
45
98
63
93
90
92
95f
2
[hmmim][ClO4] 2100
2
3
(7) De Luca, L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem.
2002, 67, 6272.
(8) Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc.
[hmim][PF6]
[hmim][BF4]
[bmim][Br]
1724
2100
3300
2
2
2
2.5
1.75
2005, 127, 11240.
(9) In a typical procedure, the oxime (0.3–1 mmol) was
dissolved in the IL (about 1 mL) and added, under stirring,
with the appropriate quantity of cyanuric chloride (TCT, 2 or
20 mol%). The mixture was left at the desired temperature
(60 °C or 130 °C) and monitored by TLC (eluant EtOAc–
light PE) until completion. The amide was isolated by direct
chromatography (silica gel) of the reaction mixture (eluant
EtOAc–light PE). Alternatively, the mixture was extracted
with MTBE (4 × 3 mL) and concentrated under vacuum. The
crude was purified on silica gel column to afford the pure
product. The amide was identified (1H NMR) by comparison
with the authentic sample. The residue of the IL was
dissolved in CH2Cl2, filtered on Celite, and reused after
removal of the organic solvent under vacuum.
20
a A solution of oxime (0.3 mmol) and TCT (2–20 mol%) in the IL (1
mL).
b Water content of the reaction mixture.
c Isolated yield by chromatography of the IL solution.
d Isolated yield by chromatography of the crude extracted with
MTBE.
e A solution of oxime (1 mmol) and TCT (2 mol%) in 1 mL of IL.
f Isolated yield after precipitation of the product with water.
Acknowledgment
(10) Ritz, J.; Fuchs, H.; Kiecza, H.; Moran, W. C. In Ullmann’s
Encyclopedia of Industrial Chemistry, 6th ed., Vol. 6;
Wiley-VCH: Weinheim, 2003, 185.
We gratefully acknowledge the financial support by MIUR and
CNR (Rome, Italy).
(11) Betti, C.; Landini, D.; Maia, A. Synlett 2006, 1335.
(12) Yadav, J. S.; Reddy, B. V. S.; Srinivas Reddy, C.;
Rajasekhar, K. Chem. Lett. 2004, 33, 476.
References and Notes
(13) (a) Landini, D.; Maia, A. Tetrahedron Lett. 2005, 46, 3961.
(b) Betti, C.; Landini, D.; Maia, A. Tetrahedron 2008, 64,
1689.
(14) Note added in proofs: The use of the IL previously treated
with a solid base (K2CO3) in order to remove residual acid
impurities, as suggested by one referee, gave the same
results. It was expected because AnalaR grade IL13b,15 were
used in our experiments.
(1) For reviews, see: (a) Gawly, R. E. Org. React. 1988, 35, 1;
and reference therein. (b) Smith, M. B.; March, J. In
Advanced Organic Chemistry, 5th ed.; John Wiley and Sons:
New York, 2001, 1415; and references therein.
(2) Sardarian, A. R.; Shahasavari-Fard, Z.; Shahasavari, H. R.;
Ebrahimi, Z. Tetrahedron Lett. 2007, 48, 2639; and
references therein.
(3) Ren, R. X.; Zueva, L. D.; Ou, W. Tetrahedron Lett. 2001, 42,
8441.
(4) Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 403.
(15) Dichiarante, V.; Betti, C.; Fagnoni, M.; Maia, A.; Landini,
D.; Albini, A. Chem. Eur. J. 2007, 13, 1834.
Synlett 2008, No. 6, 908–910 © Thieme Stuttgart · New York