Electrochemical oxidation of benzylic amines into the corresponding imines in the presence of catalytic amounts of KI

Article abstract of DOI:10.1081/SCC-200066648

Oxidation of various benzylic amines using an indirect electrochemical method was successfully carried out under very mild conditions to afford the corresponding imines in good yields. Our results show that, for this electrolytic system, the iodide ions play an important role as electron carriers. Copyright Taylor & Francis, Inc.

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Electrochemical Oxidation
of Benzylic Amines into the
Corresponding Imines in the
Presence of Catalytic Amounts
of KI
Mitsuhiro Okimoto a , Yukio Takahashi a , Kaori
Numata a , Yuji Nagata a & Gaku Sasaki a
a Department of Applied and Environmental
Chemistry , Kitami Institute of Technology , Kitami,
Hokkaido, Japan
Published online: 16 Aug 2006.
To cite this article: Mitsuhiro Okimoto , Yukio Takahashi , Kaori Numata , Yuji
Nagata & Gaku Sasaki (2005) Electrochemical Oxidation of Benzylic Amines into
the Corresponding Imines in the Presence of Catalytic Amounts of KI, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:15, 1989-1995, DOI: 10.1081/SCC-200066648
To link to this article: http://dx.doi.org/10.1081/SCC-200066648
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Synthetic Communicationsw, 35: 1989–1995, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200066648
Electrochemical Oxidation of Benzylic
Amines into the Corresponding Imines in
the Presence of Catalytic Amounts of KI
Mitsuhiro Okimoto, Yukio Takahashi, Kaori Numata,
Yuji Nagata, and Gaku Sasaki
Department of Applied and Environmental Chemistry, Kitami Institute of
Technology, Kitami, Hokkaido, Japan
Abstract: Oxidation of various benzylic amines using an indirect electrochemical
method was successfully carried out under very mild conditions to afford the corre-
sponding imines in good yields. Our results show that, for this electrolytic system,
the iodide ions play an important role as electron carriers.
Keywords: Amine, dehydrogenation, electrochemical oxidation, imine, iodine ion
Mild and efficient oxidation of amines is an important synthetic reaction in
affording the corresponding imines, which are useful organic compounds that
can introduce a new substituent at the b-position of the amine functionality.[1]
Although several oxidative methods for this transformation have been
developed to date, most require environmentally undesirable oxidants,[2]
expensive catalysts,[3] and/or long reaction periods. Our studies, in contrast,
involve the oxidation of various organic compounds using an electrochemical
method, in both the presence[4] and absence[5] of halide ions. It is well known
that the use of electric current is one of the cleanest method for the oxidation of
organic compounds.[6] Previously, electrooxidative transformation of amines to
corresponding nitriles had been reported by Shono and coworkers.[7] However,
Received in Japan October 25, 2004
Address correspondence to Mitsuhiro Okimoto, Department of Applied and
Environmental Chemistry, Kitami Institute of Technology, Koen-cyo; 165, Kitami,
Hokkaido 090-8507, Japan. Tel.: þ 81(0157) 269394; Fax: þ81(0157) 247719.
E-mail: oki@chem.kitami-it.ac.jp
1989

1990
M. Okimoto et al.
to the best of our knowledge, the electrolytic method of the oxidation of amines
into the corresponding imines, from a synthetic viewpoint, has yet to be
reported. Herein, we describe the oxidation of several benzylic amines using
our electrochemical procedure in the presence of iodide ions as the electron
carrier—this is typically referred as the indirect electrochemical oxidation.
Initially, to optimize the reaction conditions, electrooxidations were carried
out in the presence of various halide-ion sources and supporting electrolytes,
using 1,2,3,4-tetrahydroisoquinoline (1a) as the model substrate. The yields of
product 3,4-dihydroisoquinoline (2a) are listed in Table 1.
When NaOMe was used as the lone supporting electrolyte, the yield of 2a
was merely 39% (Run 1). However, the addition of a catalytic amount of KI
(3 mmol for 10 mmol of substrate) along with a strong base such as NaOMe
afforded higher yields of 2a (Runs 4–7). In the cases where KCl or KBr
was used instead of KI, 2a was obtained with yields of 66% (Run 2) and
59% (Run 3), respectively. Substituting NaI for KI as the iodide ion source
did not decrease the yield of 2a (Run 8). Detailed information on the
optimal amounts of KI and NaOMe for this electrooxidation was separately
determined, using 1a as the substrate. The yield of 2a increased with increas-
ing amounts of current; at nearly 3 F/mol, the yield reached a maximum of
90%. Excessive amounts of current (more than 3 F/mol), however, resulted
in a gradual decrease in the yield of 2a. Because most of 1a was oxidized
at the point where 2.5 F/mol of electricity was consumed, the electrooxidation
presumably proceeds through a two-electron oxidation process. In the reaction
Table 1. Electrooxidation of 1,2,3,4-tetrahydroisoquinolinea
Halogen ion
source
(3 mmol)
Supporting
electrolyte
(5 mmol)
Yieldof 2ab
(%)
Run
1
2
3
4
5
6
7
8
None
KCl
KBr
KI
NaOMe
NaOMe
NaOMe
p-TsON(Et)4
NaOAc
39
66
59
65
76
87
90
88
KI
KI
NaOH
NaOMe
NaOMe
KI
NaI
a1a: 10 mmol, MeOH: 40 mL, constant current: 0.3 A, current
passed: 3.0 F/mol, rt: ca. 158C.
bDetermind by GC analysis.

Oxidation of Benzylic Amines
1991
temperature range of 25 to 558C, favorable results were obtained at a
convenient temperature of roughly 158C.
Subsequently, several benzylic amines 1a–1k were oxidized using the
optimal reaction conditions based on the yields shown in Table 1, and the
results are listed in Table 2.
In each case, the course of the electrooxidation was monitored by
carefully measuring the composition of the reaction mixture using silica gel
TLC (ether/hexane 1:1) and GC analyses. It is important to note that the
amount of electric current necessary to complete the reaction was different
for each substrate. For example, in the cases of 1a and N-propylbenzylamine
(1b), 3.0 F/mol of electric current was sufficient to complete the reaction. In
contrast, N-cyclopentylbenzylamine (1e) required an excessive amount of
current (5.2 F/mol). Moreover, the ease of electrooxidizing alicyclic
benzylic amines 1e, 1f, and 1j was influenced by the alkyl group moiety, in
the order of cyclohexyl (3.7 F/mol) . cyclooctyl (4.5 F/mol) . cyclopentyl
(5.2 F/mol). In the cases of 1f, 1g, and 1h, based on the current passed
and the yield of products, significant substituent effects of the phenyl
group were not observed. In most cases, the corresponding imines
were successfully obtained in yields of 62 to 86%. In the case of
N-(4-tert-butylcyclohexyl)benzylamine (1i), which afforded the product
Table 2. Electrooxidative conversion of benzylic amines into the corresponding iminesa
Current passed
(F/mol)
Yieldb
of 2 (%)
Substrate
Ar
R
1a
3.0
86
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
n-Pr
iso-Pr
tert-Bu
3.0
4.5
4.0
5.2
3.7
3.7
3.7
4.5
4.5
3.2
62
74
75
71
81
83
76
66
82
75
Cyclopentyl
Cyclohexyl
Cyclohexyl
Cyclohexyl
4-tert-Bu-Cyclohexyl
Cyclooctyl
Bn
1g
1h
1i
4-MeO-C6H4
4-Cl-C6H4
Ph
Ph
Ph
1j
1k
aSubstrate: 10 mmol, KI: 3 mmol, NaOMe: 5 mmol, MeOH: 40 mL, constant current:
0.3 A, rt: ca. 158C.
bIsolated yield.

1992
M. Okimoto et al.
(66% yield) as a mixture of cis/trans isomers (ca. 1:1). In each case, the cor-
responding benzylidene-type imines were exclusively formed and alkylidene-
type imines were not detected.
Unexpectedly, attempts to electrooxidize dialkylamines were less suc-
cessful than that of the benzylic amines. For example, the electrooxidation
of butylcyclohexylamine afforded the only corresponding N-cyclohexylbuthy-
lideneamine in 53% yield (determined using GC), whereas corresponding
N-cyclohexylidenebuthylamine was not detected. Furthermore, the electro-
oxidation of dicyclohexylamine was not yield the corresponding imines; in
fact, small amount of substrates were recovered from the resulting tar-like
material, which was difficult to purify and analyze.
Although details of the reaction mechanism remain unclear, we propose
that the iodide ion plays an important role as an electron carrier in this electro-
chemical system. Specifically, the iodide ion undergoes a two-electron
oxidation process to form an iodonium ion, which then reacts with the
substrate to give an intermediate as illustrated in Scheme 1 (structure within
the bracket). The intermediate, which was not isolated, is presumably
unstable and can immediately undergo subsequent oxidation to form the
imine. In this electrochemical system, the presence of a base such as
NaOMe presumably facilitates the deprotonation of both the substrate and
the intermediate to form the final product.
The base can also function as an efficient supporting electrolyte to prevent
the increase of the terminal voltage. Moreover, the base (NaOMe) must be
produced continuously as the results of cathodic reaction, as illustrated in
Scheme 1.

Oxidation of Benzylic Amines
1993
the lower pathway of Scheme 1. Accordingly, significant increases in the
terminal voltage were observed when KI was used as the only electrolyte. If
an excessive amount of current was passed after the completion of the
reaction, the color of the electrolytic solution turned from slightly yellow to
red brown, which suggests the formation of iodine in the reaction mixture.
In conclusion, oxidations of several benzylic amines were achieved under
very mild conditions and without the use of any environmentally undesirable
reagents by means of an electrochemical method. The corresponding imines
were obtained in good to high yields, with relatively simple isolation pro-
cedures. In these electrochemical systems, the presence of iodide ions func-
tioned as electron carriers. Based on our results, we believe that our
electrochemical procedure can be applied to the oxidation of a wide variety
of benzylic amines to the corresponding imines.
EXPERIMENTAL
All electrooxidation products were identified using their physical and spectral
data. Substrates were prepared by means of usual alkylation of amines with
alkyl halide except for 1a, 1d, and 1f. 1a, 1d, and 1f were obtained from com-
mercial suppliers and were used without further purifications. Preparative-
scale electrooxidations were carried out in a tall, 50-mL beaker, equipped
with a fine frit cup as the cathode compartment, an insert cylindrical
platinum net (diameter: 32 mm, height: 35 mm, 55 mesh) as the anode, and
a nickel-coil cathode. Amines 1a–k were oxidized as follows: a solution of
substrate 1a–k (10 mmol), KI (3 mmol), and NaOMe (5 mmol) in MeOH
(40 mL) was electrooxidized under a constant current (0.3 A). During the
course of the electrooxidation, the anolyte was magnetically stirred while
the temperature of the cell was maintained at approximately 158C. GC
analyses were performed with stainless steel column (length: 2.0 m,
diameter: 5 mm) packed with 20% Apeazon L and 10% of KOH on Chromo-
sorb WAW. The gas chromatograph was equipped with a flame-ionization
detector. After completion of the electrooxidation, the reaction mixture was
concentrated in vacuo at approximately 408C to roughly one fifth of its
original volume, and the resulting residue was treated with water (30 mL)
and then extracted with ether (3 ꢀ 40 mL). The combined ether extracts
were washed with an aqueous sodium thiosulfate solution (20% w/w,
20 mL) and dried over anhydrous magnesium sulfate. After removal of the
solvent, the residue was purified by distillation under reduced pressure or
recrystallization from EtOH (the case of 1h).
N-Benzylidenepropylamine (2b): Bp 95–978C/17 hPa. IR (neat): 2961,
2932, 2874, 2831, 1647, 1450, 968, 754, 694 cm1. 1H NMR (CDCl3):
d ¼ 0.95 (t, 3 H, J ¼ 7 Hz, CH3), 1.72 (sex, 2 H, J ¼ 7 Hz, CH2), 3.55
(t, 2 H, J ¼ 7 Hz, CH2), 7.2–7.8 (m, 5 H, Ar), 8.23 (s, 1 H, N55CH).

1994
M. Okimoto et al.
13C NMR (CDCl3): d ¼ 11.85 (CH3), 24.11 (CH2), 63.52 (CH2), 128.07 (CH),
128.56 (CH), 130.43 (CH), 136.50 (C), 160.68 (CH55N). MS: m/z (%) ¼ 147
(Mþ, 18), 146 (41), 119 (28), 118 (100), 104 (21), 91 (81), 77 (13), 51 (8).
HRMS m/z found: 147.1019 (Mþ), calcd. for C10 H13 N: 147.1048.
N-Benzylidenecyclopentylamine (2e): Bp 128–1308C/19 hPa. IR (neat):
2957, 2866, 1643, 1582, 1450, 1383, 1308, 754, 694 cm1. 1H NMR
(CDCl3): d ¼ 1.4–2.2 [m, 8 H, -(CH2)4-], 3.74 (bs, 1 H, N-CH), 7.2–7.8
(m, 5 H, Ar), 8.21 (s, 1 H, N55CH). 13C NMR (CDCl3): d ¼ 24.76 (CH2),
34.53 (CH2), 71.75 (CH), 127.98 (CH), 128.43 (CH), 130.14 (CH), 136.66
(C), 158.24 (CH55N). MS: m/z (%) ¼ 173 (Mþ, 68), 172 (100), 144 (50),
130 (51), 117 (38), 104 (82), 90 (38), 89 (27), 77 (22), 41 (33). HRMS m/z
found: 173.1214 (Mþ), calcd. for C12 H15 N: 173.1204.
N-(4-Methoxybenzylidene)cyclohexylamine (2 g): Bp 140–1428C/2.6 hPa.
IR (neat): 2928, 2853, 1643, 1607, 1512, 1448, 1302, 1248, 1167, 1034,
1
831 cm1. H NMR (CDCl3): d ¼ 1.0–2.0 [m, 10 H, -(CH2)5-], 3.26 (bs, 1
H, N-CH), 3.76 (s, 3 H, CH3O), 6.86 (d, 2 H, J ¼ 9 Hz, Ar), 7.64 (d, 2 H,
J ¼ 9 Hz, Ar), 8.20 (s, 1 H, N55CH). 13C NMR (CDCl3): d ¼ 24.88 (CH2),
25.74 (CH2), 34.53 (CH2), 55.18 (CH3O), 69.76 (CH), 113.90 (CH), 129.53
(CH), 129.73 (C), 157.71 (CH55N), 161.42 (C). MS: m/z (%) ¼ 217 (Mþ,
69), 216 (62), 188 (56), 174 (64), 162 (31), 135 (34), 134 (100), 121 (31),
91 (25), 77 (24). HRMS m/z found: 217.1441 (Mþ), calcd. for C14 H19
NO: 217.1467.
N-(4-Chlorobenzylidene)cyclohexylamine (2h): Mp 53–558C. IR (KBr):
2930, 2853, 1641, 1591, 1487, 1454, 1074, 1011, 827 cm1. 1H NMR
(CDCl3): d ¼ 1.2–2.0 [m, 10 H, -(CH2)5-], 3.44 (bs, 1 H, N-CH), 7.32 (d, 2
H, J ¼ 9 Hz, Ar), 7.64 (d, 2 H, J ¼ 9 Hz, Ar), 8.23 (s, 1 H, N55CH). 13C
NMR (CDCl3): d ¼ 24.74 (CH2), 25.70 (CH2), 34.37 (CH2), 69.80 (CH),
128.72 (CH), 129.25 (CH), 135.23 (C), 136.21 (C), 157.02 (CH55N). MS:
m/z (%) ¼ 221 (Mþ, 85), 220 (39), 192 (93), 178 (84), 166 (51), 140 (58),
138 (100), 89 (65), 55 (75). HRMS m/z found: 221.0960 (Mþ), calcd. for
C13 H16 NCl: 221.0971.
N-Benzylidene-4-tert-Butylcyclohexylamine (2i): Bp 141–1458C/2.6 hPa
(mixture of cis and trans, ca. 1:1). IR (neat): 2856, 1647, 1580, 1477, 1448,
1
1393, 1366, 1310, 1061, 754, 692 cm21. H NMR (CDCl3): d ¼ 0.88, 0.90
(s, s, 9 H, tert-Bu), 1.4–2.0 (m, 9 H, -(CH2)2- ꢀ 2, CH), 3.5 (bs, 1 H,
N-CH), 7.2–7.9 (m, 5 H, Ar), 8.3 (bs, 1 H, N55CH). 13C NMR (CDCl3):
d ¼ 22.11 (CH2), 25.86 (CH2), 27.61 (CH3), 32.37 (C), 32.66 (C), 34.45
(CH2), 34.65 (CH2), 47.28 (CH), 48.58 (CH), 64.58 (CH), 70.33 (CH),
128.07 (CH), 128.43 (CH), 130.02 (CH), 130.23 (CH), 136.70 (C), 137.11
(C), 157.51 (CH55N), 158.57 (CH55N). (cis form) MS: m/z (%) ¼ 243
(Mþ, 11), 187 (18), 186 (100), 144 (33), 106 (33), 104 (26), 57 (24).
(trans form) MS: m/z (%) ¼ 243 (Mþ, 100), 228 (90), 214 (41), 186 (44),

Oxidation of Benzylic Amines
1995
144 (47), 133 (72), 106 (87), 104 (78), 91 (40), 57 (63). HRMS m/z found:
243.1958 (Mþ), 243.1975 (Mþ), calcd. for C17 H25 N: 243.1987.
N-Benzylidenecyclooctylamine (2j): Bp 132–1348C/2.6 hPa. IR (neat):
2922, 2851, 1643, 1580, 1472, 1448, 1385, 1292, 1059, 752, 692 cm1.
1H NMR (CDCl3): d ¼ 1.1–2.0 [m, 14 H, -(CH2)7-], 3.38 (bs, 1 H, N-CH),
7.2–7.8 (m, 5 H, Ar), 8.19 (s, 1 H, N55CH). 13C NMR (CDCl3): d ¼ 24.11
(CH2), 25.78 (CH2), 27.41 (CH2), 34.04 (CH2), 71.51 (CH), 128.03 (CH),
128.39 (CH), 130.10 (CH), 136.82 (C), 157.35 (CH55N). MS: m/z
(%) ¼ 215 (Mþ, 51), 214 (23), 172 (51), 158 (48), 144 (45), 132 (42), 106
(72), 104 (100), 91 (56), 41 (65). HRMS m/z found: 215.1647 (Mþ), calcd.
for C15 H21 N: 215.1674.
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