Dehydroaromatization with V2O5

Article abstract of DOI:10.1055/s-0033-1339277

Vanadium pentoxide is evaluated as a dehydroaromatization reagent. Tetrahydrocarbazole is readily aromatized by V₂O₅ in refluxing acetic acid under both stoichiometric and catalytic conditions. Indoline, tetrahydroquinoline, and tetrahydroquinoxaline are effectively aromatized by V₂O₅/silica in refluxing toluene. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1339277

LETTER
▌1675
letter
Dehydroaromatization with V O
2
5
2 5
Dehydroaromatization with V O
Megha Karki, Hugo C. Araujo, Jakob Magolan*
Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
Fax +1(208)8856173; E-mail: jmagolan@uidaho.edu
Received: 01.04.2013; Accepted after revision: 24.05.2013
We found that tetrahydrocarbazole (3) is inert to stoichio-
Abstract: Vanadium pentoxide is evaluated as a dehydroaromati-
metric V O in refluxing acetonitrile and dioxane, howev-
2
5
zation reagent. Tetrahydrocarbazole is readily aromatized by V O
2
5
er, trace conversion into carbazole is observed in toluene
ditions. Indoline, tetrahydroquinoline, and tetrahydroquinoxaline after four hours (Table 1, entries 1–3). Product formation
in refluxing acetic acid under both stoichiometric and catalytic con-
are effectively aromatized by V O /silica in refluxing toluene.
occurs smoothly in acetic acid with complete substrate
conversion in two days and 79% yield of carbazole (4)
isolated (Table 1, entries 4–6). With 2.0 equivalents of
V O the reaction time is reduced to 24 hours with slightly
2
5
Key words: oxidation, arenes, heterocycles, vanadium pentoxide,
carbazoles
2
5
improved product yield (Table 1, entry 7). Catalytic V O
2
5
with excess co-oxidants di-tert-butyl peroxide (DTBP)
and H O are modestly successful with conversions of
Metal oxides occupy a prominent role in industrial
catalysis enabling many important transformations such
1
2
2
4
6% and 37%, respectively, after 24 hours reaction time
as catalytic photodegradation of organics in waste water
2
(Table 1, entries 8 and 9). Other co-oxidants including O2
(1 atm) and benzoquinone are less effective (<10% con-
version).
treatment and manufacture of formaldehyde from metha-
3
nol. Catalytic oxidative dehydrogenation (ODH) is an in-
dustrial process for the synthesis of ethylene and other
4
short-chain alkenes 2 from corresponding alkanes 1.
Table 1 Conversion of Tetrahydrocarbazole (3) into Carbazole (4)
ODH is performed at high temperature (>400 °C) over
mixed metal oxide catalysts (Scheme 1).
V2O5
O2, metal oxide(s), support
conditions
N
N
H
H
1
> 400 °C
2
3
4
Scheme 1
Conversiona
(yield, %)
Entry V O
Solvent
Temp (°C) Time
(h)
2
5
b
(
equiv)
Vanadium pentoxide (V O ), the most stable and common
2
5
1
2
1.0
1.0
1.0
1.0
1.0
1.0
2.0
0.2c
0.2d
0.2
0.05
MeCN
dioxane
toluene
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOHe
82
101
111
118
118
118
118
118
118
118
118
4
4
0
naturally occurring vanadium species, is the most fre-
quently used component of the various mixed-oxide cata-
0
5
lysts shown to be effective in ODH processes. Given its
3
4
2
prominence in this role, we chose to investigate the suit-
ability of V O for dehydroaromatization of more com-
4
4
39
2
5
plex substrates at less destructive temperatures.
5
24
48
24
24
24
72
96
59
6
Vanadium pentoxide and several other oxovanadium
7
complexes have been previously used to mediate various
6
>99 (79)
98 (83)
46
oxidative transformations.
7
We began by investigating the conversion of tetrahydro-
carbazole (3) into carbazole (4, Table 1). Similar reactions
are commonly accomplished using 2,3-dichloro-5,6-di-
8
9
37
8
cyano-1,4-benzoquinone (DDQ) or catalytic palladium-
9
10
>99 (80)
98 (68)
on-carbon (Pd/C) in high-boiling solvents, which have re-
placed reagents such as chloranil, SeO , MnO , elemental 11
2
2
1
0
sulfur, and selenium. In terms of cost and toxicity, V O
2
5
a
b
c
d
e
1
Determined by H NMR spectroscopy.
Isolated yield after chromatography.
DTBP (3.0 equiv) was added.
H O (30% aq, 3.0 equiv) was added.
Solvent degassed by Ar bubbling for 10 min; reaction run under Ar
compares favorably with DDQ. Employment of Pd/C for
dehydrogenations is inherently limited to substrates with-
out labile olefins.
2
2
atmosphere.
SYNLETT 2013, 24, 1675–1678
Advanced online publication: 12.07.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Surprisingly, complete conversion of tetrahydrocarbazole
DOI: 10.1055/s-0033-1339277; Art ID: ST-2013-S0291-L
Georg Thieme Verlag Stuttgart · New York
(
3) into carbazole (4) is also observed when catalytic V O
2 5
©

1676
M. Karki et al.
LETTER
(
0.2 equiv) is employed in the absence of an added termi- Table 3 summarizes the results of dehydroaromatization
nal oxidant (Table 1, entry 10). Even with 5 mol% of experiments with eight substrates. The first four substrates
V O , under an argon atmosphere in degassed acetic acid, (Table 3, entries 1–4), without basic N–H moieties, are
2
5
complete conversion is achieved in 3.5 days (Table 1, en- most effectively dehydrogenated in acetic acid. N-Acetyl
1
try 11). We observe trace ethyl acetate in the crude H indoline (7) is unreactive in toluene and slow to dehydro-
NMR spectra of these reactions presumably resulting genate in acetic acid (Table 3, entries 2a and 2b). With 2
from reduction of acetic acid to ethanol. We thus hypo- equivalents of V O complete substrate consumption re-
2
5
thesize that acetic acid is acting as the terminal oxidant.
quires 6 days, and N-acetyl indole (8) is obtained in 61%
yield (Table 3, entry 2a). When V O loading is reduced
2
5
A number of efficient and green dehydrogenations of
1
1
to 5 mol% just 28% conversion is observed after 8 days
Table 3, entry 2b).
amines to be generally ineffective in acetic acid. For ex- Dihydro- and tetrahydronaphthalenes (9 and 11) react
ample, treatment of indoline (5) with stoichiometric V O poorly under these conditions. Treatment of dihydronap-
in acetic acid results in no reaction apart from trace forma- thalene (9) with 2 equivalents of V O in refluxing AcOH
amines have appeared in the literature in recent years.
We find V O -mediated dehydroaromatizaiton of cyclic
(
2
5
2
5
2
5
tion of N-acetyl indoline (Table 2, entry 1). We hypothe- for 4 days results in incomplete conversion of the sub-
size that protonation of the amine by the solvent yields an strate and only 36% isolated yield of naphthalene (10, Ta-
ammonium acetate species that is inert to oxidation by ble 3, entry 3). Tetrahydronapthalene (11) is essentially
V O .
unreactive with just 4% conversion into naphthalene ob-
servable by H NMR spectroscopy after four days (Table
2
5
1
Table 2 Conversion of Indoline (5) into Indole (6)
3
, entry 4). The next three substrates, all nitrogen-contain-
V2O5
ing heterocycles, are inert to V O in refluxing acetic acid
2
5
but are readily aromatized by V O /silica in refluxing tol-
2
5
N
conditions
N
uene both with excess V O and catalytic V O with ex-
H
H
2
5
2
5
5
6
cess DTBP as a terminal oxidant offering indole (6),
quinoline (14), and quinoxaline (16) in good yields (Table
3, entries 5–7). In all three cases, employment of catalytic
V O requires longer reaction times than the correspond-
Entry V O5 SiO2
Solvent Temp Time Conv.a
2
b
(
equiv) (mg/mmol 5)
(°C)
(h)
(yield, %)
2
5
1
2
3
4
5
6
7
1.2
1.2
1.2
1.2
1.2
0
–
AcOH
118
111
111
111
111
111
111
4
4
n/ac
60
ing stoichiometric reaction. Treatment of tetrahydroiso-
quinoline (17) with two equivalents of V O for 48 hours
2
5
–
toluene
toluene
toluene
toluene
toluene
toluene
consumes all of the substrate and yields a mixture of 3,4-
dihydroisoquinoline (18) and isoquinoline (19) that can be
isolated in modest yields (25% and 31%, respectively; Ta-
ble 3, entry 8). In the case of tetrahydroisoquinoline (17)
use of catalytic V O and excess DTBP is not viable yield-
–
22
22
22
22
40
76
200
800
800
86
96 (82)
33
2
5
ing a complex mixture of products.
Finally, we demonstrate a one-pot Fischer indole synthe-
sis–dehydrogenation sequence that enables the prepara-
0.2d
800
98 (75)
1
2
a
b
c
1
tion of two carbazoles directly from phenyl hydrazine
Determined by H NMR.
Isolated yield after chromatography.
Only starting material and trace N-acetyl indoline were observable
(20) and cyclohexanones (21) using V O (2 equiv) in re-
2
5
fluxing acetic acid (Scheme 2). Carbazole (22) and 3-tert-
butylcarbazole (23) are obtained in 76% and 74% yield,
respectively, after a 48 hour reaction time.
1
by H NMR.
d
DTBP (2.0 equiv) was added.
R
However, replacement of the acetic acid solvent with tol-
uene results in successful dehydrogenation of indoline (5)
to indole (6, Table 2, entries 2 and 3). The reaction is im-
proved by addition of silica gel (Table 2, entries 4 and 5),
our goal being to crudely mimic ‘industrial’ oxidative de-
hydrogenation conditions. Addition of 800 mg of silica
per mmol of substrate increases conversion to 96% in
R
V2O5 (2 equiv)
+
AcOH, reflux
4
8 h
N
H
NHNH2
20
O
21
22, R = H, 76%
2
3, R = t-Bu, 74%
22 hours with 82% isolated yield of indole.
Scheme 2
A control reaction performed in the absence of vanadium
reveals that silica alone also mediates partial dehydroge-
nation of indoline (Table 2, entry 6, 33% conversion).
In conclusion, our evaluation of the capacity of V O to
mediate dehydroaromatization reactions has resulted in a
number of synthetically useful examples of this approach.
2
5
Catalytic V O with excess DTBP (2.0 equiv) and silica
2
5
(
800 mg/mmol of substrate) are also effective conditions Such dehydrogenations are commonly accomplished us-
resulting in 75% yield of indole after 40 hours reaction
time (Table 2, entry 7).
ing more expensive and/or more toxic catalysts or re-
Synlett 2013, 24, 1675–1678
© Georg Thieme Verlag Stuttgart · New York

LETTER
Dehydroaromatization with V O5
1677
2
agents such as Pd/C and DDQ. Vanadium pentoxide is a towards further mechanistic elucidation and additional
common industrial catalyst and represents an inexpensive applications of the V O /AcOH system are presently un-
2
5
alternative that is suitable for select substrates.
der way.
Vanadium pentoxide is also an effective oxidant for a
two-step, one-pot carbazole formation via Fischer indole
synthesis and dehydrogenation. Notably, catalytic V O
Representative Experimental Procedures
2
5
effectively dehydrogenates tetrahydrocarbazole to carba-
Indoline to Indole (Cat. V O , DTBP, Silica, Toluene)
2
5
zole in refluxing acetic acid. In this case, we hypothesize Indoline (1.0 mmol), V
O (0.2 mmol), di-tert-butyl peroxide (3.0
2
5
mmol), silica gel (800 mg, Sorbent Technologies, particle size 40–
that the solvent plays the role of terminal oxidant. Efforts
Table 3 Dehydroaromatization Experiments with Eight Substrates
Entry
Conditionsa
Substrate
Product(s)
Time (h)
Yield (%)b
1
1
1
a
b
c
V O (2.0 equiv), AcOH
24
48
96
83
79
68
2
5
V O (1.0 equiv), AcOH
2
5
N
N
H
H
V O (0.05 equiv), AcOH
2
5
3
4
2
2
a
b
V O (2.0 equiv), AcOH
N
N
144
192
61
2
5
V O (0.05 equiv), AcOH
Ac
(28)c
2
5
Ac
7
9
1
8
3
4
V O (2.0 equiv), AcOH
96
96
36
2
5
10
12
V O (2.0 equiv), AcOH
(4)c
2
5
1
5
5
a
b
V O (1.2 equiv), SiO , toluene
22
40
82
75
2
5
2
N
N
H
V O (0.2 equiv), DTBP, SiO , toluene
H
2
5
2
5
6
6
6
a
b
V O (2.0 equiv), SiO , toluene
41
108
75
61
2
5
2
N
N
V O (0.2 equiv), DTBP, SiO , toluene
H
2
5
2
1
4
1
3
5
H
N
N
N
7
7
a
b
V O (2.0 equiv), SiO , toluene
24
84
88
79
2
5
2
V O (0.2 equiv), DTBP, SiO , toluene
N
H
2
5
2
1
6
8
1
N
N
1
1
1
8 25
9 31
NH
8
V O (2.0 equiv), SiO , toluene
48
2
5
2
17
19
a
Reactions were performed in refluxing AcOH, 118 °C, or refluxing toluene, 111 °C; where SiO is indicated, 800 mg SiO per mmol of sub-
2
2
strate were used; where DTBP is indicated, 3.0 equiv were used.
b
Isolated yield after chromatography.
Product was not isolated and yield was estimated based on crude mass recovery and H NMR analysis of reaction mixture.
c
1
©
Georg Thieme Verlag Stuttgart · New York Synlett 2013, 24, 1675–1678

1678
M. Karki et al.
LETTER
6
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was stirred at reflux temperature under an Ar atmosphere and mon-
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through a Celite plug. The solids were washed repeatedly with
CHCl . The combined filtrate was concentrated in vacuo and puri-
fied by silica gel chromatography (EtOAc–hexanes) to give indole
3
4
070.
1
13
in 75% yield. NMR ( H and C) spectra matched those of an au-
thentic sample.
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(
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Indoline to Indole (V O , Silica, Toluene)
2
5
Indoline (1.0 mmol), V O (2.0 mmol), silica gel (800 mg), and tol-
2
5
uene (6 mL) were added to a round-bottomed flask equipped with a
stir bar and reflux condenser. The reaction mixture was stirred at re-
flux temperature under an Ar atmosphere and monitored by TLC.
After 22 h the reaction was cooled and filtered through a Celite
plug. The solids were washed repeatedly with CHCl . The com-
bined filtrate was concentrated in vacuo and purified by silica gel
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1
13
NMR ( H and C) spectra matched those of an authentic sample.
Tetrahydrocarbazole to Carbazole (Cat. V O , AcOH)
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2
5
Tetrahydrocarbazole (1.0 mmol), V O (0.05 mmol), and AcOH (6
2
5
mL) were added to a round-bottomed flask equipped with a stir bar
and reflux condenser. The reaction mixture was stirred at reflux
temperature under an Ar atmosphere for 5 d. The reaction was
cooled to r.t., H O was added, and the aqueous layer was extracted
2
three times with CHCl . The combined extracts were washed with
3
brine and dried over Na SO , concentrated in vacuo, and the residue
2
4
was purified by column chromatography (EtOAc–hexanes) to offer
1
13
carbazole in 68% yield. NMR ( H and C) spectra matched those
of an authentic sample.
(
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One-Pot Fischer Indole Synthesis and Dehydrogenation
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equipped with a stir bar and reflux condenser. The reaction mixture
was stirred at reflux temperature under an Ar atmosphere for 48 h.
2
003, 68, 2944. (h) Murase, N.; Hoshino, Y.; Oishi, M.;
2
5
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layer was extracted three times with CHCl . The combined extracts
3
(
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2
4
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1
(
EtOAc–hexanes) to offer carbazole in 76% yield. NMR ( H and
C) spectra matched those of an authentic sample.
1
3
5
0, 4669.
(
9) For representative examples, see: (a) Archer, S.; Ross, B. S.;
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2
(
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