Oxidation of aldimines to amides by m-CPBA and BF3·OEt2

Article abstract of DOI:10.1016/S0040-4039(03)00156-4

Several amides were obtained in high yields by an efficient method from the corresponding imines which are readily prepared from aldehydes. This procedure involves the oxidation of aldimines with m-CPBA and BF₃·OEt₂. In this reaction, the product is strongly influenced by the electron releasing capacity of the aromatic substituent.

Full text of DOI:10.1016/S0040-4039(03)00156-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2183–2186
Oxidation of aldimines to amides by m-CPBA and BF3·OEt2
Gwang-il An,a Misoo Kim,b Jin Yeon Kimc and Hakjune Rheea,*
aDepartment of Chemistry, Hanyang University, Ansan, Kyunggi-Do 425-791, Republic of Korea
bDepartment of Basic Science, Hankyong National University, Ansung, Kyunggi-Do 456-749, Republic of Korea
cDepartment of Chemistry, Seonam University, Namweon, Chunrabuk-Do 590-170, Republic of Korea
Received 20 September 2002; revised 27 December 2002; accepted 10 January 2003
Abstract—Several amides were obtained in high yields by an efficient method from the corresponding imines which are readily
prepared from aldehydes. This procedure involves the oxidation of aldimines with m-CPBA and BF3·OEt2. In this reaction, the
product is strongly influenced by the electron releasing capacity of the aromatic substituent. © 2003 Elsevier Science Ltd. All
rights reserved.
Numerous methods for the oxidation of aldehydes have
been reported over the years.1 We developed a simple
one-pot procedure for the conversion of aldehydes to
methyl esters via dimethyl acetal formation from alde-
hydes and subsequent oxidation.2 The proposed oxida-
tion mechanism involves the formation and rapid
fragmentation of the peroxy intermediate II, as shown
below (Scheme 1). Other alkyl acetals and cyclic acetals
were also readily converted to the corresponding esters
by the same methodology.3
shows a plausible competitive reaction mechanism for
the oxidation of imines to amides by m-CPBA with
BF3·OEt2.
If the reaction proceeds as in the acetal oxidation, the
amide would be the only product formed via an inter-
nal hydrogen abstraction. If the reaction proceeds via
the formation of an oxaziridine, one might expect the
selective rearrangement of the aryl group or the hydro-
gen atom as in the Beckmann rearrangement and the
Baeyer–Villiger oxidation. We now wish to report an
oxidation of aldimines to amides by m-CPBA and
BF3·OEt2. The results are summarized in Table 1.7
Although a number of oxidation methods for the con-
version of aldehydes to amides have been reported, a
few of these proceed through imines.4 Since imines are
readily prepared from the corresponding aldehydes,5 it
would be expected that the imine carbon could likewise
be activated via the coordination of the Lewis acid,
BF3·OEt2 on the lone pair of nitrogen atom as occurs
on the oxygen atom in the acetal oxidation. Another
possible reaction pathway could be through an
oxaziridine intermediate since there is literature prece-
dent for the formation of oxaziridines from the corre-
sponding imines with peroxyacid.6 Thus, Scheme 2
The results in Table 1 would indicate that the reaction
product is strongly influenced by the electron releasing
capacity of the aromatic substituent. With the electron-
releasing substituent on the aryl group (entries 1–3 and
9–10), the oxidation of imines afforded formamides in
which aryl group migration occurred. However, an
electron-withdrawing substituent on the aryl group pro-
vided the amide formed from hydride migration (entries
5–8). In the case of the chloro substituent (entry 4), the
Scheme 1.
Keywords: oxidative rearrangement; aldimines; migratory aptitude; formamides; amides.
* Corresponding author. E-mail: hrhee@hanyang.ac.kr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00156-4

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G. An et al. / Tetrahedron Letters 44 (2003) 2183–2186
formamide was obtained as the major product (83% yield)
along with 5.6% of the amide. These results suggest that
the reaction mechanism can be tentatively rationalized by
the oxaziridine ring formation and Lewis acid mediated
ring opening with subsequent migration of the aryl group
or the hydrogen atom, depending on the difference in the
migratory aptitude of those groups to an electron deficient
nitrogen atom (Scheme 2, bottom). Thermal reaction
studies of the oxaziridines by Splitter and Calvin8 and the
oxidative rearrangement of aldimines with sodium per-
borate by Ramsden and co-worker4b,c support the reac-
tion mechanism shown in the bottom of Scheme 2.
Contrary to our results, however, their procedures gave
very poor selectivity and yield in the oxidative rearrange-
ment of aldimines.
In contrast to entries 1–10, when p-anisidine is used for
the oxidation of aldimine (entries 11–14), the oxidation
affords only the N-(p-methoxyphenyl)-p-substituted-
benzamide along with a considerable amount of the
recovered arylaldehyde. It is presumed that the reaction
follows an internal hydrogen abstraction (Scheme 2, top)
and decomposition to the corresponding aldehyde. The
electron releasing group, i.e. the methoxy group of
p-anisidine, increases the electron density on the nitrogen
atom and helps the coordination of the Lewis acid on the
lone pair of the nitrogen atom. After the formation of
the peroxy intermediate by the attack of m-CPBA on the
iminium carbon, rapid fragmentation of the peroxy
intermediate presumably occurs to provide the amide
(Scheme 2).
Scheme 2.
Table 1. Oxidation of aldimines to amides by m-CPBA and BF3·OEt2
Entry
Imine
Product
Yield (%)a
1
2
3
4
5
6
7
8
C6H5CHꢀNC6H5
p-Me-C6H4CHꢀNC6H5
p-MeO-C6H4CHꢀNC6H5
p-Cl-C6H4CHꢀNC6H5
p-NO2-C6H4CHꢀNC6H5
p-NC-C6H4CHꢀNC6H5
HCON(C6H5)2
82
90
HCONC6H5 p-Me-C6H4
HCONC6H5 p-MeO-C6H4
HCONC6H5 p-Cl-C6H4
p-NO2-C6H4CONHC6H5
p-NC-C6H4CONHC6H5
91
89b
71
79
75
71
80
p-F3C-C6H4CHꢀNC6H5
C6F5CHꢀNC6H5
p-F3C-C6H4CONHC6H5
C6F5CONHC6H5
9
trans-C6H5CHꢀCH-CHꢀNC6H5
trans-C6H5CHꢀCMe-CHꢀNC6H5
C6H5CHꢀN p-MeO-C6H4
p-Me-C6H4CHꢀN p-MeO-C6H4
p-MeO-C6H4CHꢀN p-MeO-C6H4
p-Cl-C6H4CHꢀN p-MeO-C6H4
C6H5CHꢀN p-Cl-C6H4
p-Me-C6H4CHꢀN p-Cl-C6H4
p-MeO-C6H4CHꢀN p-Cl-C6H4
p-Cl-C6H4CHꢀN p-Cl-C6H4
HCONC6H5 trans-C6H5CHꢀCH
HCONC6H5 trans-C6H5CHꢀCMe
C6H5CONH p-MeO-C6H4
p-Me-C6H4CONH p-MeO-C6H4
p-MeO-C6H4CONH p-MeO-C6H4
p-Cl-C6H4CONH p-MeO-C6H4
HCONC6H5 p-Cl-C6H4
HCON p-Me-C6H4 p-Cl-C6H4
HCON p-MeO-C6H4 p-Cl-C6H4
HCON(p-Cl-C6H4)2
10
11
12
13
14
15
16
17
18
82
42c
45d
52e
39f
84
84
86
82g
a Yields refer to isolated products.
b Formamide and amide were obtained in a 14.8: 1 ratio.
c Benzaldehyde was also isolated in 51% yield.
d p-Tolualdehyde was also isolated in 50% yield.
e p-Anisaldehyde was also isolated in 43% yield.
f p-Chlorobenzaldehyde was also isolated in 51% yield.
g N-(p-Chlorophenyl)-p-chlorobenzamide was also isolated in 7% yield.

G. An et al. / Tetrahedron Letters 44 (2003) 2183–2186
2185
However, with an electron withdrawing group, i.e. the
chloro group of p-chloroaniline (entries 15–18), the
reaction products were the same as in the aniline cases
and also follow the oxaziridine ring formation and
Lewis acid mediated ring opening with the subsequent
migration of the aryl group or the hydrogen atom to
the electron deficient nitrogen atom.
6. (a) Kitagawa, O.; Velde, D. V.; Dutta, D.; Morton, M.;
Takusagawa, F.; Aube´, J. J. Am. Chem. Soc. 1995, 117,
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7. General procedure for the preparation of aldimines: To a
solution of aryl carboxaldehyde, trans-cinnamaldehyde,
or trans-a-methylcinnamaldehyde (5 mmol) in CHCl3 (20
mL) were added aniline, p-anisidine, or p-chloroaniline
(10 mmol) and molecular sieves (1.0 g) at ambient tem-
perature. After stirring for a certain period of time, the
crude mixture was rinsed with K2CO3–brine solution
(3×20 mL) and the crude product was concentrated by
rotary-evaporation. The purity of the crude products was
checked by 1H NMR spectroscopy. The products were
sufficiently pure to use for next reaction.
1
The products of this oxidation were identified by a H
NMR comparison with that of known compounds
(entries 1–8, 11–16, 18).4b,c,9 Otherwise, these were fully
1
characterized by IR, H and 13C NMR, and HRMS
analysis (entries 9, 10, 17).10–12 In the case of the
electron-withdrawing substituent on the aryl group
(entries 5–8) and in p-anisidine (entries 11–14), a deu-
terium exchange of the amide NH was observed in the
1H NMR spectra.
In summary, we have developed an efficient method for
the conversion of various aldimines to their correspond-
ing N,N-diarylformamides or amides by m-CPBA and
BF3·OEt2. The hydrolysis of N,N-diarylformamides will
provide diarylamines and this method could be a valu-
able alternative to the Chapman rearrangement13 and
the Ullmann–Goldberg condensation.14
General procedure for the preparation of amides: To a
solution of aldimine (5 mmol) in anhydrous CHCl3 (15
mL) were added m-CPBA (72%, 5.0 mmol) in anhydrous
CHCl3 (15 mL) and BF3·OEt2 (1.5 mmol) at 0°C. The
resulting reaction mixture was stirred for 6 h at ambient
temperature. The reaction mixture was diluted with
CHCl3 (15 mL) and washed with saturated Na2CO3
solution (3×20 mL). The organic layer was dried over
anhydrous MgSO4 and concentrated by rotary-evapora-
tion. The residue was purified by flash column chro-
matography (EtOAc/n-hexane).
Acknowledgements
This work, carried out in 2001, was supported by
Hanyang University, Korea. M.K. would also like to
thank the Hankyong National University Research
Fund for providing partial support in 2001.
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10. The characterization of N-phenyl-N-trans-styrylform-
amide: IR (thin film) 3060, 2879, 1685, 1643, 1495, 1228,
950, 693, 585 cm−1
CH
10H, ArH
(CDCl3) l 161.0, 138.0, 136.0, 130.2, 129.1, 128.8, 128.2,
127.2, 126.1, 125.3, 115.7; HRMS (EI) m/z: calcd for
(C15H13NO): 223.0997, found 223.0986 [M+].
;
1H NMR (CDCl3) l 8.27 (s, 1H,
6
O), 7.99 (d, J=15.0 Hz, 1H, CH
6
ꢀC), 7.18–7.56 (m,
6
), 5.85 (d, J=14.7 Hz, 1H, CH
6
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1
1685, 1595, 1493, 1301, 1270, 1246, 745 cm−1; H NMR
(CDCl3) l 8.65 and 8.55 (pair of s, 1H, CH
6
O), 7.24–7.46
ꢀC),
(m, 10H, ArH), 6.56 and 6.54 (pair of br s, 1H, CH
6
6
2.14 and 1.97 (pair of d, J=1.5 and 1.2 Hz, 3H, MeCꢀC);
13C NMR (CDCl3) l 161.5, 161.0, 137.3, 136.6, 135.6,
135.4, 129.7, 129.5, 129.3, 129.0, 128.8, 128.6, 128.4,
127.5, 127.3, 127.2, 126.9, 126.3, 125.8, 123.9, 17.9, 17.3;
HRMS (EI) m/z: calcd for (C16H15NO): 237.1154, found
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1
cm−1; H NMR (CDCl3) l 8.63 and 8.52 (pair of s, 1H,
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