E. Rancan et al. / Catalysis Communications 54 (2014) 11–16
15
Table 4
Reactivity of CyC with HOA. Run conditions: CyC 10 mmol, HOA 30 mmol.
Entry
Temp.
°C
Time
h
Reagents
Molar ratio
CH3CN
Conversion
%
Selectivity
%
H2O
COX
CPL
Notes
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
90
90
90
90
90
15
1
15
1
15
1
15
1
3
5
1
15
1
10
10
10
/
/
/
/
/
/
/
99
79
95
71
93
60
77
76
90
94
92
99
62
90
98
98
44
56
41
66
61
79
54
23
5
13
/
85
85
/
/
Pitchesb
14
25
15
11
/
Byproductsc
Pitches, byproducts
Byproducts
Pitches, byproducts
Byproducts
Biphasic, byproducts
Pitches, byproducts
Pitches, byproducts
Pitches
Pitches, byproducts
Pitches
/
90
90
20
20
/
/
/
/
/
20
/
/
/
5
100
100
100
110
110
110
110
110
10
10
10
10
10
/
39
72
61
61
/
5
1
/
Byproducts
Byproducts
Pitches
1
15
/
/
a
Reaction was carried out in the presence of 4 equivalents of pyridine with respect to COX.
Pitches are insoluble brown to black condensation products of complex structure.
GC–MS analysis showed several products of condensation, isomerization and various chlorinated compounds.
b
c
to AcA ranging from 80 to 90% (entries 3, 8–11, Table 2). The main
byproduct of the reaction is aniline (Anl), thus suggesting that reaction
proceeds in almost quantitative conversion to AcA, but deacetylation
(likely via hydrolysis) of AcA to Anl occurs as a consecutive reaction
after the rearrangement. The decrease in AcA selectivity is also accom-
panied by the continuous increase of the pitches over time, whose com-
position, studied by GC–MS analysis, shows variable mixtures of
phenylaniline, quinone immine and a complex mixture of condensation
and chlorination products. The nature of these pitches is similar to that
of aniline-black dyes obtained from Anl oxidation, [35].
The reactions carried out in the presence of water as a solvent
(entries 5–7, Table 3), showed low conversion and APO as the only
major product. This suggests that the presence of water is even more
critical for the Beckmann rearrangement of APO (for comparison with
4-HAPO see entries 5 and 6, Table 2). As a matter of fact, it is likely
that the acidity of the HCl, released after the oximation, in water is not
sufficient to achieve APO rearrangement.
When the reaction was attempted in solventless conditions it
appears that at 90 °C, after 15 h a moderate conversion and a very low
selectivity in AcA (ca. 5%) was obtained (entry 4, Table 3). At 110 °C
the rearrangement appeared to be negligible, in fact, after 1 h of reaction
APO selectivity is 95%, AcA is detected only in traces, and the rest is
mainly condensation products (entry 13, Table 3). At the same reaction
condition but longer reaction time (15 h) the conversion was 95%, but
the selectivity to APO is decreased to 5%, AcA is present as traces, Anl
is the main product reaching 54% of selectivity, and pitches and heavy
condensation products are also present in the reaction mixture (entry
14, Table 3). The presence of Anl suggests that the Beckmann rearrange-
ment occurs, but the negligible selectivity to AcP is due to consecutive
and parallel reactions, which are responsible of AcP consumption.
In Table 4 the reactivity of CyC with HOA is reported. Also in this case
the presence of HCl appears essential to achieve CPL since COX was the
only product formed in the presence of pyridine (entry 1, Table 4).
Under the same reaction conditions, the conversion of CyC was lower
than that of the aromatic ketones (4-HAP and AP). As a matter of fact,
in the case of CyC the Beckmann rearrangement step appears to
be more inhibited compared to the aromatic ketones. This is in agree-
ment with the relative reactivity of the corresponding oximes to the
Beckmann rearrangement in mineral acid [16,32].
crucial to achieve high selectivity to the desired product. Even though,
the optimization of the reaction condition is beyond the scope of this
preliminary work it is evident that under the proper condition CyC
may show both high conversion and synthetically interesting selectivity
to CPL (entry 11, Table 4). Compared to data reported in Table 1, where
CH3CN did not seem to influence the selectivity, here, the solvent could
play an important role in the reaction outcome (entries 1, 3, 4, 9–13,
Table 4). In fact, only in the presence of CH3CN the selectivity to CPL
reaches values interesting from a synthetic point of view. For instance,
at 90 °C, after 3 h of reaction and in the presence of CH3CN as a sol-
vent/promoter, it was achieved a conversion of 90% with 72% selectivity
toward CPL. In the absence of solvent, the reaction resulted in only a
modest selectivity toward amides (entries 4, 5, 14 and 15, Table 4).
Most probably, the large amount of pitches observed also at low tem-
perature might inhibit the acid catalyzed Beckmann rearrangement.
As a matter of fact, oximation of ketone to COX occurred, but the HCl
formed, necessary for its rearrangement, is consumed in other side reac-
tions. This is in agreement with the presence of chlorinated compounds
detected by GC–MS analysis. The negligible selectivity to CPL and the
quite high selectivity to COX observed in the presence of water (entries
7 and 8, Table 4) suggest that the rearrangement needs an acidity higher
than that achieved by the HCl, formed during the oximation step, in the
presence of water [33,34].
4. Conclusion
In this work we report for the self-catalyzed direct amidation of ke-
tones. The conversion of various ketones to amides has been investigat-
ed. Results achieved are particularly interesting for the substrates,
whose production presents environmental and plant concerns that
could be solved by an industrial implementation of this reaction. It is
noteworthy that in these reaction conditions, acetaminophen could be
obtained in one-pot from 4-hydroxyacetophenone oxime in almost
quantitative yield without any solvent or acid catalyst.
Acetanilide and caprolactam were also obtained in high yields in the
presence of CH3CN which is an easily recyclable solvent.
The reaction appears to follow the one-pot oximation-Beckmann
rearrangement reaction path; a two stage process whose steps
are well known reactions. In this way, the control of the overall
process for industrial application appears to be easy and of simple
implementation.
The selectivity to CPL are generally not comparable with those of the
aromatic ketones because cyclohexanone has strong tendencies to con-
dense, therefore the control of the reaction parameters is even more