Beckmann rearrangement of ketoximes to lactams by triphosphazene catalyst

Article abstract of DOI:10.1021/jo702277g

(Chemical Equation Presented) Triphosphazene, 1,3,5-triazo-2,4,6- triphosphorine-2,2,4,4,6,6-chloride (TAPC), was found to be an efficient catalyst for the Beckmann rearrangement of cyclohexanone oxime and cyclododecanone oxime to ε-caprolactam and laurolactam, which are raw materials of nylon-6 and nylon-12, respectively.

Full text of DOI:10.1021/jo702277g

phase Beckmann rearrangement of cyclohexanone oxime to
ꢀ-caprolactam using a high-silica zeolite catalyst,4 and has
operated since 2003. On the other hand, Ishihara and co-workers
reported the first successful Beckmann rearrangement of ke-
toximes to lactams by an organocatalyst, cyanuric chloride
(CNC), without formation of any sulfate.5 This method provides
a convenient route to lactams from oximes, but the rearrange-
ment of cyclohexanone oxime to ꢀ-caprolactam, which is the
most important Beckmann rearrangement in industrial chemistry,
was difficult to carry out in satisfactory yield by CNC catalyst:
even by the use of 10 mol % of CNC, the yield of ꢀ-caprolactam
was only 30% under refluxing acetonitrile.
Beckmann Rearrangement of Ketoximes to
Lactams by Triphosphazene Catalyst†
Masaharu Hashimoto, Yasushi Obora,
Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Chemistry and Material Engineering, Faculty of
Chemistry, Materials and Bioengineering & High Technology
Research Center, Kansai UniVersity, Suita,
Osaka 564-8680, Japan
ishii@ipcku.kansai-u.ac.jp
Recently, we have developed the one-pot synthesis of lactams
from cycloalkanes such as cyclohexane and cyclododecane,6
which consists of the nitrosation of cycloalkanes with tert-butyl
nitrite using N-hydroxyphthalimide (NHPI) catalyst followed
by the isomerization to oximes and then the Beckmann
rearrangement by CNC.7 Furthermore, we disclosed that the
Beckmann rearrangement of cyclohexanone oxime to ꢀ-capro-
lactam by CNC catalyst can be improved by carrying out the
reaction in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a sol-
vent. During the course of this study, our attention is focused
on the development of a new catalyst other than the Ishihara
catalyst, CNC, for the Beckmann rearrangement of oximes to
lactams under mild conditions. Fortunately, we have now found
that triphosphazene, 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-
chloride (TAPC), is an efficient catalyst for the Beckmann
rearrangement of various ketoximes to lactams (eq 1). Interest-
ingly, TAPC promotes efficiently the Beckmann rearrangement
of cyclohexanone oxime to ꢀ-caprolactam, which is difficult to
achieve satisfactorily by CNC.
ReceiVed October 22, 2007
Triphosphazene, 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-
chloride (TAPC), was found to be an efficient catalyst for
the Beckmann rearrangement of cyclohexanone oxime and
cyclododecanone oxime to ꢀ-caprolactam and laurolactam,
which are raw materials of nylon-6 and nylon-12, respec-
tively.
The Beckmann rearrangement of oximes to lactams is a very
important commercial process for the production of raw
materials of polyamides such as nylon-6 and nylon-12.1,2
Currently, the Beckmann rearrangement is carried out using
oleum as a catalyst, which results in undesired sulfates as
byproducts.3 It is generally said that at least 1.7 tons of sulfates
are formed to obtain a ton of the ꢀ-caprolactam. In the year
2005, ca. 4 million tons of ꢀ-caprolactam was manufactured in
the world. As a result, vast amounts of sulfates are co-produced
with the lactam. Therefore, much effort has been devoted so
far to the development of the sulfate-free synthetic method of
lactams, in particular, in industrial chemistry. In recent years,
Sumitomo Chemical of Japan has developed a new process for
sulfate-free lactam synthesis, involving the oximation of cy-
clohexanone with NH3 and H2O2 on TS-1 and then the vapor-
The Beckmann rearrangement of cyclododecanone oxime (1a)
to laurolactam (2a) which is an important raw material of nylon-
12 was chosen as a model reaction and was examined using
several candidate catalysts which seem to promote the Beck-
mann rearrangement of oximes (Table 1).
The activity of various catalysts for the rearrangement of 1a
to 2a was compared with that of cyanuric chloride (CNC)
reported by Ishihara et al.5 The reaction of 1a by CNC (1 mol
%) in MeCN (2 mL) at 70 °C for 2 h afforded 2a in 22% yield
(entry 1), while the same reaction by TAPC (1 mol %) gave 2a
in 64% (entry 2). In order to improve the catalytic efficiency
of the reaction, we examined the effect of various solvents in
this transformation. From reactions in various solvents, the
rearrangement was found to proceed smoothly by allowing the
reaction in fluorinated solvents. For instance, the reaction in
† This paper is dedicated to the memory of the late Professor Yoshihiko Ito.
(1) (a) Luedeke, V. D. In Encyclopedia of Chemical Processing and
Design; Mcketta, J. J., Ed.; Marcel Dekker: New York, 1978; pp 72-95.
(b) Rademacher, H. In Ullmann’s Encyclopedia of Industrial Chemistry,
5th ed.; Gerhartz, W., Ed.; Wiley: New York, 1987; Vol. A8, pp 201-
203. (c) Weber, J. N. In Kirk-Othmer Encyclopedia of Chemical Technology,
4th ed.; Kroschwitz, J. I., Ed.; Wiley: New York, 1990; Vol. 19, pp 500-
501. (d) Wessermel, K.; Arpe H.-J. Industrial Organic Chemistry, 4th ed.;
Wiley-VCH: Weinheim, Germany, 2003; pp 239-266.
(2) For recent examples of transition-metal-catalyzed Beckmann rear-
rangement of oximes, see: (a) Owston, N. A.; Parker, A. J.; Williams, J.
M. J. Org. Lett. 2007, 9, 3599. (b) Owston, N. A.; Parker, A. J.; Williams,
J. M. J. Org. Lett. 2007, 9, 73. (c) Park, S.; Choi, Y.; Han, H.; Yang, S. H.;
Chang, S. Chem. Commun. 2003, 1936.
(4) (a) Takahashi, T.; Kai, T.; Nakao, E. Appl. Catal. A 2004, 262, 137.
(b) Forni, L.; Fornasari, G.; Giordano, G.; Lucarelli, C.; Katovic, A.; Trifiro`,
F.; Perri, C.; Nagy, J. B. Phys. Chem. Chem. Phys. 2004, 6, 1842 and
references cited therein.
(5) Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2005,
127, 11240.
(3) Fisher, W. B.; Crescentini, L. In Kirk-Othmer Encyclopedia of
Chemical Technology, 4th ed.; Kroschwitz, J. I., Ed.; Wiley: New York,
1990; Vol. 4, pp 827-839.
(6) Hashimoto, M.; Sakaguchi, S.; Ishii, Y. Chem. Asian J. 2006, 1, 712.
(7) Hirabayashi, T.; Sakaguchi, S.; Ishii, Y. Angew. Chem., Int. Ed. 2004,
43, 1120.
10.1021/jo702277g CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/05/2008
2894
J. Org. Chem. 2008, 73, 2894-2897

TABLE 1. The Beckmann Rearrangement of 1a to 2a by Various
Catalystsa
On the basis of these results, we next examined the Beckmann
rearrangement of various ketoximes to lactams using TAPC
catalyst (Table 2). 1-Phenylethanone oxime (1b) was reacted
under several conditions (entries 1-4). It was found that 1b
was perfectly rearranged to N-phenylacetamide (2b) by TAPC
(1 mol %) in HFIP at 70 °C, while the same reaction in MeCN
gave 2b in moderate yield (44%) (entries 1 and 2). However,
the reaction by the use of 2 mol % of TAPC under refluxing
temperature (ca. 80 °C) of MeCN led to 2b in quantitative yield
(entry 4). 1-(4-Methylphenyl)ethanone oxime (1c) and 1-(2-
naphthalenyl)ethanone oxime (1d) were smoothly rearranged
by TAPC even in MeCN to N-(4-methylphenyl)acetamide (2c)
at 70 °C and N-(2-naphthyl)acetamide (2d) at refluxing tem-
perature, respectively (entries 5-8). 2,4-Dimethyl-3-pentanone
oxime (1e) was also rearranged to 2-methyl-N-(1-methylethyl)-
propanamide (2e) in quantitative yield (entries 9 and 10). These
results indicate that TAPC possesses high catalytic activity for
the Beckmann rearrangement of ketoximes to lactams. The most
attractive application of TAPC to the Beckmann rearrangement
is the reaction of cyclohexanone oxime (4) to ꢀ-caprolactam
(5) (Scheme 1, eq 2). Thus, 4 was allowed to react in the
presence of TAPC under several reaction conditions (Table 3).
yield/%b
catalyst
(mol %)
entry
solvent
MeCN
MeCN
HFIP
HFIP
HFIP
HFIP
conv/%b
22
2a
22
3a
1
2
3
CNC (1)
TAPC (1)
CNC (1)
TAPC (1)
CNC (0.1)
CNC (0.1)
TAPC (0.1) HFIP
TAPC (0.3) HFIP
CNC (1)
TAPC (1)
CNC (1)
TAPC(1)
CNC(1)
TAPC(1)
TAPF (2)
TICNA (1)
TICNA (1)
CNA (5)
NBSf (1)
NCSg (1)
trace
trace
trace
0
trace
trace
trace
68
64
>99
>99
20
47
86
>99
>99
19
4
5c
6c,d
7d,e
8d
9
47
86
>99
99(96) trace
CF3CF2CH2OH 20
CF3CF2CH2OH 74
11
71
1
4
10
6
3
94
6
4
1
1
2
5
4
0
2
1
10
11
12
13
14
15
16
17
18
19
20
AcOH
AcOH
tBuOH
tBuOH
HFIP
HFIP
MeCN
HFIP
4
8
19
13
5
96
8
SCHEME 1. One-Pot Synthesis of 5 from 4
no reaction
25
26
HFIP
HFIP
22
25
trace
trace
a 1a (1.0 mmol) was allowed to react in the presence of catalyst in solvent
(2 mL) at 70 °C (bath temperature) for 2 h. b By GLC. The number in the
parentheses shows isolated yield. c 1a (10 mmol) and HFIP (10 mL) were
used. d Reaction time was 6 h. e 1a (5 mmol) and HFIP (5 mL) were used.
f N-Bromosuccinimide. g N-Chlorosuccinimide.
Treatment of 4 with 1-2 mol % of TAPC in HFIP led to only
small amounts of 5 (7-13%) and its condensate (6) (3-7%)
as well as cyclohexanone (7) (1%) (entries 1 and 2). When the
amount of TAPC was increased to 5 mol %, 4 was rearranged
to 5 (40%) and 6 (26%) in 4 h (entry 4). The condensate product
6 was found to be easily hydrolyzed to 2 equiv of 5 in
quantitative yield (98% isolated yield) (Scheme 1, eq 3). This
means that 4 can be rearranged to 5 in an overall yield of 92%
by TAPC. In order to compare the catalytic activity of TAPC
with that of CNC,5 the reaction using CNC under the same
conditions was used, but the reaction gave only 5 (16%), 6 (7%),
and 7 (1%) (entry 5). These results indicate that TAPC is more
active than CNC for the Beckmann rearrangement of 4 to 5
under these conditions. In addition, one-pot synthesis of 5 from
4 was performed under the same conditions as those described
in Table 3, entry 4, followed by the hydrolysis according to the
method as shown in eq 3. As a result, 5 was obtained in 82%
isolated yield.
HFIP instead of MeCN gave 2a in quantitative yields by both
CNC and TAPC catalysts (entries 3 and 4). However, when
the amount of CNC or TAPC was reduced to 0.1 mol % with
respect to 1a, the yield of 2a was 47% by CNC and 86% by
TAPC (entries 6 and 7). By the use of 0.3 mol % of TAPC, 1a
was completely rearranged to 2a in 6 h (entry 8). The reaction
of 1a by CNC (1 mol %) in 2,2,3,3,3-pentafluoro-1-propanol
resulted in 2a (11%) and cyclododecanone (3a) (4%), while by
TAPC, 2a was obtained in 71% yield and 3a was less than 1%
(entries 9 and 10). The reaction in common solvents such as
acetic acid and tert-butyl alcohol led to 2a in poor yields (entries
11-14). The catalytic performance of several catalysts for the
rearrangement of 1a to 2a was examined in HFIP and MeCN
(entries 15-20). 1,3,5-Triazo-2,4,6-triphosphorine-2,2,4,4,6,6-
fluoride (TAPF), which is an analogue of TAPC, was found to
be inactive, and the starting TAPF was recovered unchanged
after the reaction (entry 15). Trichloroisocyanuric acid (TICNA)
indicated relatively high catalytic activity in HFIP but low in
MeCN (entries 16 and 17). Cyanuric acid (CNA) was inactive,
but NBS and NCS indicated low catalytic activities (entries 18
and 20).
Scheme 2 shows a plausible reaction path for the Beckmann
rearrangement of 4 by TAPC. It was found that no product was
formed by the reaction of TAPC with HFIP at 70 °C for 2 h.
Rosini et al. reported that a stoichiometric reaction of oxime 4
with TAPC affords O-(pentachlorocyclotriphosphazatriene)-
J. Org. Chem, Vol. 73, No. 7, 2008 2895

TABLE 2. The Beckmann Rearrangement of Various Ketoximes by TAPCa
a Oxime (1) (1 mmol) was allowed to react with TAPC (1 mol %) in solvent (2 mL) at 70 °C (bath temperature) or refluxing temp (ca. 80 °C) for 2 h.
b By GLC. The numbers in the parentheses show isolated yields. c TAPC (2 mol %) was used.
TABLE 3. The Beckmann Rearrangement of Cyclohexanone
Oxime (4) by TAPC or CNC under Various Conditionsa
SCHEME 2. A Plausible Reaction Path for the Beckmann
Rearrangement by TAPC
yield/%b
catalyst
(mol %)
entry
solvent
conv/%b
5
6
7
1
2
TAPC (1)
TAPC (2)
TAPC (5)
TAPC (5)
CNC (5)
TAPC (5)
TAPC (5)
TAPC (5)
HFIP
HFIP
HFIP
HFIP
HFIP
MeCN
MeCN
HFIP
22
33
88
>99
49
39
67
56
7
3
1
1
2
13
34
40
16
11
20
25
7
18
26
7
3
1
3
4c
5c
6
trace
1
5
13
8
7d
8e
4
a 4 (1.0 mmol) was allowed to react in the presence of catalyst in solvent
(2 mL) at 70 °C (bath temperature) for 2 h. b By GLC. c Reaction time
was 4 h. d Refluxing temp (ca. 80 °C). e H2O (0.2 mL) was added.
cyclohexanone (A) in 63% yield.8 Therefore, we thought that
the compound A is a key intermediate to lactam 5. Thus, 4 was
reacted in the presence of a catalytic amount (0.1 equiv) of A
prepared independently by modified Rosini’s procedure under
several conditions. It is interesting to note that the reaction of
4 (1 mmol) in the presence of A (0.1 equiv) in HFIP (2 mL) at
70 °C for 2 h afforded 5 (47%) and 6 (15%), while the same
reaction in MeCN gave very low yield of 5 (5%).
The rearrangement from A to lactam 5 is considered to
proceed through the formation of nitrilium ion B followed by
nucleophilic attack of H2O to produce 5. The dimeric condensate
6 seems to be formed through the reaction of the resulting 5
(8) (a) Rosini, G.; Baccolini, G.; Cacchi, S. J. Org. Chem. 1973, 38,
1060. (b) Trunbull, J. H. Chem. Ind. 1956, 350.
2896 J. Org. Chem., Vol. 73, No. 7, 2008

with B. In fact, the addition of water in HFIP resulted in a
considerable decrease of the condensate 6 (Table 3, entry 8).
We confirmed that 6 is not produced by the reaction of oxime
4 with lactam 5 even in the presence of HFIP (eq 4).
bottomed flask. Then the mixture was stirred at 80 °C for 2 h.
The solvent was removed under reduced pressure, extracted with
diethyl ether, and the compound 5 (221 mg, 98%) was obtained
by evaporation of ether.
One-Pot Synthesis of 5 from 4 (Scheme 1): A mixture of
TAPC (0.1 mmol, 35 mg) and HFIP (4 mL) was placed in a 30
mL round-bottomed flask, and 4 (2 mmol, 226 mg) was added
to the flask. Then the mixture was stirred at 70 °C for 4 h.
After the solvent was removed under vacuum, methanesulfonic
acid (0.25 mmol, 24 mg), H2O (10 mmol, 180 mg), and tBuOH
(4 mL) were added to this concentrate, then the reaction mixture
was stirred at 80 °C for 2 h. Removal of the solvent under
reduced pressure and purification by column chromatography
on silica gel (ethyl acetate/MeOH ) 10/1) gave a fraction of 5
containing HFIP. H2O (ca. 2 mL) was added to this and
evaporated the solvent, giving 5 in 82% yield (186 mg).
The products 2a,5 2b,5 2c,9 2d,5 2e,5 5,10 and 610 are known
compounds and have been reported previously.
In conclusion, we have found that TAPC, easily available
from commercial source, serves as an efficient catalyst for the
Beckmann rearrangement of ketoximes to lactams. The rear-
rangement of cyclohexanone oxime (4) to ꢀ-caprolactam (5)
which was not fully succeeded by CNC was achieved by TAPC.
The present method provides an environmentally friendly route
to nylon-6 without formation of any salt.
Experimental Section
All starting materials were commercially available and used
without any purification. GLC analysis was performed with a
flame ionization detector using a 0.22 mm × 25 m capillary
column (BP-5 or BP-25). 1H NMR and 13C NMR spectra were
measured at 270 and 67.5 MHz, respectively. Chemical shifts
were reported in parts per million (δ) relative to tetramethyl-
silane (Me4Si) in CDCl3.
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research on Priority Areas “Advanced
Molecular Transformation of Carbon Resources” from the
Ministry of Education, Culture, Sports, Science and Technology,
Japan, “High-Tech Research Center” Project for Private Uni-
versities: matching fund subsidy from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, 2005-2009, and
Research Association for Ishii Oxidation Technology.
Typical Procedure for the Reaction of 1a (Table 1, entry
8): A mixture of TAPC (0.01 mmol, 3.5 mg) and HFIP (2 mL)
was placed in a 20 mL round-bottomed flask, and 1a (1 mmol,
197 mg) was added to the flask. Then the mixture was stirred
at 70 °C for 2 h. After removal of the solvent under reduced
pressure, 2a (190 mg) was isolated by column chromatography
on silica gel (n-hexane/ethyl acetate ) 1/1) in 96% yield.
Synthesis of 5 from 6 (eq 3): A mixture of 6 (1 mmol, 208
mg), methanesulfonic acid (0.25 mmol, 24 mg), H2O (10 mmol,
Supporting Information Available: Copies of 1H and 13C
spectra for 2a-e, 5, and 6. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO702277G
(9) Katritzky, A. R.; Cai, C.; Singh, S. K. J. Org. Chem. 2006, 71, 3375.
(10) Mazurkiewicz, R. Acta Chim. Hung. 1990, 127, 439; Chem. Abstr.
1991, 114, 206 693.
t
180 mg), and BuOH (2 mL) was placed in a 20 mL round-
J. Org. Chem, Vol. 73, No. 7, 2008 2897