Electrochemical dehydrogenation of 1,2,3,4-tetrahydroisoquinoline to 3,4-dihydroisoquinoline

Article abstract of DOI:10.3987/COM-04-10247

Dehydrogenation of 1,2,3,4-tetrahydroisoquinoline to 3,4-dihydroisoquinoline was carried out using an electrochemical method in the presence of KI. In this method, the iodide ion presumably played an important role as an electron carrier.

Full text of DOI:10.3987/COM-04-10247

HETEROCYCLES, Vol. 65, No. 2, 2005
371
HETEROCYCLES, Vol. 65, No. 2, 2005, pp. 371 - 375
Received, 12th October, 2004, Accepted, 26th November, 2004, Published online, 3rd December, 2004
ELECTROCHEMICAL DEHYDROGENATION OF 1,2,3,4-
TETRAHYDROISOQUINOLINE TO 3,4-
DIHYDROISOQUINOLINE
＊
Mitsuhiro Okimoto, Yukio Takahashi, Kaori Numata, and Gaku Sasaki
Department of Applied and Environmental Chemistry
Kitami Institute of Technology, Koen-cyo 165, Kitami, Hokkaido 090-8507, Japan
ꢀꢀꢀ E-mail: oki@chem.kitami-it.ac.jp
ꢀ
Abstract - Dehydrogenation of 1,2,3,4-tetrahydroisoquinoline to 3,4-
dihydroisoquinoline was carried out using an electrochemical method in
the presence of KI. In this method, the iodide ion presumably played
an important role as an electron carrier.
INTRODUCTION
Oxidation of amines to the corresponding imines is not frequently encountered, and accordingly, the
1
scope of these reactions is rather limited. In the case of the oxidation of 1,2,3,4-tetrahydroisoquinoline
(
1a), a cyclic amine, to 3,4-dihydroisoquinoline (2a), the reported methods involve environmentally
2
3
undesirable oxidants, expensive catalysts, and/or long reaction periods. In our laboratory, oxidation of
several organic compounds, especially those containing a nitrogen atom, has been carried out using an
4
electrochemical method in the presence of halogen ion. ꢀAlthough it is well known that the use of
5
electric current is one of the cleanest method for the oxidation of organic compounds, to the best of our
knowledge, the electrochemical method for the oxidation of 1a to 2a has not been reported. Herein, we
report on the novel electrochemical dehydrogenation of 1a using iodide ions as the electron carrier.
RESULTS AND DISCUSSION
Initially, to optimize the reaction conditions, oxidation of 1a was performed in the presence of various
halogen ion sources and bases. The results of these reactions, along with the yields of 2a, are listed in
Table 1.

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HETEROCYCLES, Vol. 65, No. 2, 2005
a
Table 1. Oxidation of 1,2,3,4-Tetrahydroisoquinoline (1a)
Oxidation
N
N
H
2a
1
a
b
Halogen ion source
3 mmol)
Base
(5 mmol)
Yield of 2a
Run
(
(
%)
1
2
3
4
5
6
7
none
KCl
KBr
KI
NaOMe
NaOMe
NaOMe
NaOAc
NaOH
41
66
59
76
87
90
88
KI
KI
NaOMe
NaOMe
NaI
a
Reaction conditions: 1a, 10 mmol; MeOH, 40 mL; Constant
current, 0.3 A; Current passed, 3.0 F/mol; ca.15 ℃.
b
Determind by GC analysis.
When NaOMe was used as the lone supporting electrolyte, the yield of 2a was merely 41% (Run 1).
However, the addition of a catalytic amount of KI, along with a base (especially a strong base such as
NaOMe) was favorable in affording higher yields of 2a (Runs 4-6). When KCl (Run 2) or KBr (Run 3)
was used instead of KI, the yields of 2a were 66 and 59 %, respectively. Substitution of NaI for KI as
the iodide ion source did not decrease the yield of 2a (Run 7). Optimal amounts of KI and NaOMe for
this electrooxidation were separately determined using 1a as the substrate. On the other hand, as shown
in the relationship between the current passed and yield (Figure 1), the yield of 2a increased with an
increase in amount of current passed until nearly 3 F/mol, and finally reached to just 90%. Current in
excess of 3 F/mol resulted in a gradual decrease in the yield of 2a. Because most of the substrate was
consumed at the stage where 3 F/mol of electricity had been passed, the electrooxidation presumably
involves a two-electron oxidation process.

HETEROCYCLES, Vol. 65, No. 2, 2005
373
1
00
N
5
0
0
2a
0
1
2
3
4
5
Current passed (F/mol)
Figure 1. Relationship between current passed and yield of 2a
Subsequently, based on the results obtained from the preliminary examinations, the electrochemical
oxidation of 1a and other benzylic amines (1b) and (1c) was carried out, and the results were shown in
Table 2. The course of the electrochemical dehydrogenation was carefully monitored by analyzing the
composition of the reaction mixture using silica gel TLC (ether/hexane 1:1) and GC. In each case,
electrolytic current was applied until the substrate was nearly completely consumed. As in the case of
1
a, electrochemical dehydrogenation of 1b and 1c to the corresponding imines (2b) and (2c) was
successful; the yields of isolated imines (2b) and (2c) were 76 and 81%, respectively. Unexpectedly,
the electrochemical dehydrogenation of an alicyclic amine, such as dicyclohexylamine, was unsuccessful,
resulting in a tar-like material that was difficult to purify.
a
Table 2. Oxidation of Benzylic Amines
1
1
2
2
R
R
R
R
Oxidation
N
a-c
N H
a-c
2
1
b
Substrate
Current Passed
(F/mol)
Yield of 2a-c
%)
1
2
(
R
R
1
1
1
a
-(CH ) -
2 2
3
.0
.0
86
76
81
b H
tert-Bu
4
c
H
Cyclohexyl
3.7
a
b
Reaction conditions: 1a-c, 10 mmol; KI, 3 mmol; NaOMe, 5 mmol;
MeOH, 40 mL; Constant current, 0.3 A; ca.15℃.
Isolated yields based on substrates.

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HETEROCYCLES, Vol. 65, No. 2, 2005
Although the reaction mechanism remains unclear, it appears that the iodide ion plays an important role
as the electron carrier in this 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 (illustrated
as the structure in brackets in Scheme 1).
Anode
-2e
+
+
-
+
+
I - H
- I - H
N
N
N
H
I
base
base
Scheme 1
In this electrolysis 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. Furthermore, the
base can also function as an efficient supporting electrolyte (the terminal voltage of the electrolytic cell
was always maintained at less than 10V). In conclusion, the electrooxidative transformation of some
benzylic amines to the corresponding imines was achieved under very mild conditions, and without the
use of environmentally undesirable reagent. In each case, isolation of the resulting imines was
relatively simple.
EXPERIMENTAL
The structure of the products was identified using their physical and spectral data. All reagents were
obtained from commercial suppliers and were used without further purifications. Preparative-scale
electrochemical oxidation was carried out in a tall 50-mL beaker, equipped with a fine frit cup as the
cathode compartment, an insert cylindrical platinum net (diameter, 30 mm; height, 34 mm; 55 mesh) as
the anode, and a nickel coil cathode. Amines (1a – c) were oxidized as follows: a solution of substrate
1
a – c (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 reaction, the anolyte was magnetically stirred while
maintaining the temperature of the cell at approximately 15±2 ºC. GC analyses were performed with
stainless steel column (length:1.5 m, diameter:5 mm) packed with 20% Apeazon L and 10% of KOH on
2
Chromosorb W AW. N served as the carrier gas. The gas chromatograph was equipped with a flame
ionization detector. After completion of the electrochemical dehydrogenation, the reaction mixture was

HETEROCYCLES, Vol. 65, No. 2, 2005
375
concentrated in vacuo at approximately 40 ºC to roughly one-fifth of its original volume, and the resulting
residue was treated with water (30 mL), 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.
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