Efficient synthesis of N-alkyl-2,7-dihalocarbazoles by simultaneous carbazole ring closure and N-alkylation

Article abstract of DOI:10.1016/j.tet.2012.04.044

The N-alkyl-2,7-dihalocarbazole as the main product was formed by the reaction of 4,4′-dihalo-2-nitrobiphenyl with aromatic nitro compound and trialkyl phosphite. The presence and crucial role of aromatic nitro compound causes simultaneous carbazole ring closure and N-alkylation unlike the Cadogan ring closure where non-alkylated carbazole is formed as a main product. In addition, the mixture of aromatic nitro compound and trialkyl phosphite was found to be a possible N-alkylating agent for heterocycles, such as carbazole or indole.

Full text of DOI:10.1016/j.tet.2012.04.044

Tetrahedron 68 (2012) 5075e5080
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of N-alkyl-2,7-dihalocarbazoles by simultaneous carbazole ring
closure and N-alkylation
Drahomír V yꢀ prachtick yꢀ , Ivan Kmínek, Veronika Pokorna, Vera Cimrova
*
ꢀ
ꢁ
ꢀ
*
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsk yꢀ Sq. 2, 162 06 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
0
Article history:
The N-alkyl-2,7-dihalocarbazole as the main product was formed by the reaction of 4,4 -dihalo-2-
nitrobiphenyl with aromatic nitro compound and trialkyl phosphite. The presence and crucial role of
aromatic nitro compound causes simultaneous carbazole ring closure and N-alkylation unlike the Ca-
dogan ring closure where non-alkylated carbazole is formed as a main product. In addition, the mixture
of aromatic nitro compound and trialkyl phosphite was found to be a possible N-alkylating agent for
heterocycles, such as carbazole or indole.
Received 1 February 2012
Received in revised form 23 March 2012
Accepted 10 April 2012
Available online 19 April 2012
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Carbazole ring closure
Carbazole alkylation
Heterocycles
Aromatic substitution
Conjugated polymers
1. Introduction
2,7-dihalocarbazole as a single product. In the case that the desired
product is N-alkyl-2,7-dihalocarbazole, the Cadogan or Freeman
Carbazoles have received considerable attention in the literature
ring closure must be followed by carbazole N-alkylation. However,
1
because of their widespread occurrence in both natural and syn-
the efficient (three-step) procedures were developed for the
2
7
thetic materials. In synthetic materials, carbazoles are an important
preparation of N-alkyl-2,7-dichlorocarbazole and N-alkyl-2,7-
8
building block for both low-molecular-weight and polymer mate-
rials. The 2,7-conjugated carbazole based organic polymers and
copolymers have become the theme of significant scientific and
industrial research in recent years for numerous optoelectronic
dibromocarbazole only. In the case of the diiodo derivative,
a more complicated five-step synthesis based on an azide strategy
7,9
10
was reported. Recently, we reported a novel three-step syn-
thesis of N-(2-ethylhexyl)-2,7-diiodocarbazole (1), which repre-
sents a significant simplification of the formerly known five-step
procedure based on the azide strategy. In our synthesis (Scheme
3
applications, such as organic light-emitting diodes, solar cells, and
field effect transistors. The synthesis of high-molecular-weight
polymers requires, among others, the 2,7-dihalocarbazole mono-
mers. From the organic chemistry viewpoint, the preparation of
,7-dihalosubstituted carbazoles is not as straightforward as the
synthesis of 3,6-substituted examples. The positions meta to the
0
1) the 4,4 -diiodobiphenyl (2) was nitrated (step 1) yielding a mix-
0
0
ture of 4,4 -diiodo-2-nitrobiphenyl (3) and 4-iodo-4 -nitrobiphenyl
(4). The isolated compound 3 was converted (step 2) via Cadogan or
Freeman ring closure into 2,7-diiodocarbazole (5), which was then
alkylated (step 3) with 2-ethylhexyl bromide to 1. Moreover it was
shown that whereas the application of triethyl phosphite mediated
Cadogan ring closure just on 3 led to the expected 5, the same per-
formance on the mixture of compounds 3þ4 afforded the N-ethyl-
2,7-diiodocarbazole (6) as a major product (Scheme 1). Such in-
teresting results with the mixture of 3þ4 evoked our investigation
of the role of aromatic nitro compound in carbazole ring closure.
In this paper we have explored the above mentioned phenom-
enon and we report about the crucial role of the aromatic nitro
compound in carbazole ring closure. We found out that the addi-
tion of simple nitro aromatic compound to the Cadogan ring
closure leads to simultaneous carbazole ring closure and its N-al-
kylation. The mechanism considering the formation of trialkyl
2
amino group of carbazole unit cannot be functionalized directly
0
by electrophilic aromatic substitution. Therefore, 4,4 -dihalo-
2
2
-nitrobiphenyl precursor units are used to synthesize
,7-substituted carbazoles via heterocyclic ring closure. The Cado-
4
0
gan ring closure of 4,4 -dihalo-2-nitrobiphenyl by means of triethyl
phosphite provides the 2,7-dihalocarbazole as a major product and
5
the unwanted N-ethyl-2,7-dihalocarbazole as a minor product.
6
The Freeman’s modification of Cadogan ring closure by means
of triphenylphosphine was developed to provide just the
*
Corresponding authors. Tel.: þ420 296 809 251; fax: þ420 296 809 410; e-mail
addresses: vyprach@imc.cas.cz (D. V yꢀ prachtick yꢀ ), cimrova@imc.cas.cz (V. Cimrov aꢀ ).
0
040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.044

5076
D. V yꢀ prachtick yꢀ et al. / Tetrahedron 68 (2012) 5075e5080
(
8gei), and carbazole11 (8jem). The yields of N-alkyl-2,7-
dihalocarbazole varied between 40 and 80% depending on the al-
kyl phosphite and X-substituent. In the case of heavy halogen
substituent (X¼Br, I), the yield of 7 increases with a size of alkyl in
the used alkyl phosphite (ethyl<butyl<2-ethylhexyl). On the other
hand, for relatively lightweight chlorine or hydrogen as sub-
stituents (X¼Cl, H) the tendency seems to be opposite. Just the
results gained with 2-nitrobiphenyl (X¼H) indicate that the yields
are more likely connected with the weight of X rather than with its
electronegativity. The isolated yields of the side product 8 were
found to be low (1e6%) and one could say negligible. Except the
case of R¼2-ethylhexyl and X¼Cl or H, where the yields for 8i and
Scheme 1. Three-step synthesis of N-(2-ethylhexyl)-2,7-diiodocarbazole (1).
8m were determined as 24 and 35%, respectively. It is not clear now
why we recovered the 2,7-dihalocarbazole more efficiently just in
these two cases although the reaction time here was even increased
from 5 to 17 h (Table 1). We should shortly comment the reaction
N-arylphosphorimidate or dialkyl N-arylphosphoramidate in
alkylation process is suggested.
0
condition, which led to data given in Table 1. The 4,4 -dihalo-2-
2
2
. Results and discussion
nitrobiphenyl and 4-nitrotoluene were mixed in molar ratio 1:1.5
for the best yield. More nitro compound did not increase the yield
and moreover caused the problem in column chromatography. The
trialkyl phosphite was used in 5 mol excess per both reaction
components. It was more than theoretical value 3.5 mol (2 mol for
ring closureþ1.5 mol for nitro compound) and adequate for re-
action workup. More trialkyl phosphite caused problem in the next
chromatographic separation and did not increase the yield. The
excess of triethyl or tributyl phosphites was removed by vacuum
distillation before chromatography. In the case of tris(2-ethylhexyl)
.1. Synthesis of N-alkyl-2,7-dihalocarbazoles
Simple aromatic compounds, such as nitrobenzene or
-nitrotoluene were tested at first. Starting 4,4 -dihalo-2-
0
4
nitrobiphenyl and 4-nitrotoluene were heated with an excess of
trialkyl phosphite in argon. Simultaneous carbazole ring closure
and N-alkylation yielding the N-alkyl-2,7-dihalocarbazole (7) as
a main product and 2,7-dihalocarbazole (8) as a side product was
0
ꢀ
followed by TLC (4,4 -dihalo-2-nitrobiphenyl disappeared after
phosphite (bp 446 C) it was difficult and the reaction mixture had
3
e4 h) and the products 7 and 8 were isolated by column chro-
to be chromatographed without vacuum distillation.
matography (Table 1). The prepared new materials 7aem were
1
13
characterized by TLC, elemental analysis, melting point, H and
C
2.2. Simultaneous carbazole ring closure and N-alkylation
NMR and FTIR. The non-alkylated carbazole derivatives 8 were
10
identified by means of separately prepared 2,7-diiodocarbazole
To reveal more about simultaneous carbazole ring closure and
N-alkylation mechanism we analyzed the reaction mixture f (Table
8
7
(
8aec), 2,7-dibromocarbazole (8def), 2,7-dichlorocarbazole
1) in more detail. As we mentioned above the separation of prod-
ucts 7 and 8 was performed by column chromatography on silica
gel in toluene/heptane (1:1 by vol). Then we applied gradient elu-
tion chromatography increasing the solvent polarity to ethyl ace-
tate and ethyl acetate/acetone (3:1 by vol) and we released the
more polar reaction intermediates from the column. These frac-
tions were analyzed by GCeMS and the reaction intermediates
were determined as 2-ethyl-1-hexanol, tris(2-ethylhexyl) phos-
phite, tris(2-ethylhexyl) phosphate, and bis(2-ethylhexyl) N-(4-
tolyl)phosphoramidate. The possibility of carbazole ethylation in
triethyl phosphite mediated Cadogan ring closure by means of
Table 1
Simultaneous carbazole ring closure and N-alkylation yielding the N-alkyl-
,7-dihalocarbazole (7) as a main product and 2,7-dihalocarbazole (8) as a side
product
2
0
diethyl N-(2 ,6-dimethylbiphenyl-2-yl)phosphoramidates or tri-
0
ethyl N-(2 ,6-dimethylbiphenyl-2-yl)phosphorimidates was sug-
5
gested and, consequently, we decided to prove such reaction
mechanism in our system. From a mechanism point of view, we
suppose that the simultaneous carbazole ring closure and N-al-
kylation shown in Table 1 consists of three steps, which take place
more or less simultaneously in a one pot reaction arrangement. The
first step includes the trialkyl phosphite mediated carbazole ring
Entrya
R
X
Yieldb (%)
7
8
a
b
c
d
e
f
g
h
i
Ethyl
n-Butyl
2-Ethylhexyl
Ethyl
n-Butyl
2-Ethylhexyl
Ethyl
n-Butyl
2-Ethylhexyl
Ethyl
n-Butyl
I
I
I
38
44
60
57
63
70
74
73
62
81
82
48
1
1
5
3
1
6
1
1
4
closure known as Cadogan ring closure. The second step repre-
4
,12,13
Br
Br
Br
Cl
Cl
Cl
H
H
H
sents the also known
formation of trialkyl N-arylphosphor-
imidate or dialkyl N-arylphosphoramidate from aromatic nitro
compound and trialkyl phosphite. Finally, the third step, the car-
bazole alkylation by the phosphoramidate or phosphorimidate
derivative, was proved separately with prepared model com-
pounds. The diethyl N-(4-tolyl)phosphoramidate (9) was synthe-
sized from 4-nitrotoluene and triethyl phosphite according to
24
2
2
j
k
m
2-Ethylhexyl
35
12
recently published procedure by Beifuss et al. The triethyl N-(4-
tolyl)phosphorimidate (10) was prepared by a thermal de-
oxygenation reaction from 4-nitrotoluene and triethyl phosphite
a
0
Reaction condition: the 4,4 -dihalo-2-nitrobiphenyl and 4-nitrotoluene (1:1.5
by mol) were mixed under argon in trialkyl phosphite (5 mol excess per both re-
ꢀ
action components) and heated at 160 C for 5 h (aeh, j, k) or 17 h (i, m), and then
13
according to procedure described by Sundberg et al. The reaction
procedure is depicted in Scheme 2.
chromatographed (Silica gel 60) in toluene/heptane (1:1 by vol).
b
Isolated yields by column chromatography.

D. V yꢀ prachtick yꢀ et al. / Tetrahedron 68 (2012) 5075e5080
5077
the ring closure is not active here. The 2.8 mol excess per
-nitrotoluene was found to be sufficient and optimal for reaction
4
workup. The N-(2-ethylhexyl)carbazole (12) was isolated in a rea-
sonable yield (55%) by column chromatography on silica gel in tol-
uene/heptane (1:1 by vol). When the 4-nitrotoluene was replaced
with other aromatic nitro compound, such as nitrobenzene, the al-
kylation of 11 took place with a similar yield of 12, but the product
separation was more complicated. In particular, the column chro-
matography on silica gel was necessary to combine with that on
aluminum oxide. However, the alkylation reaction was not observed
if the nitro aromatic compound was replaced with aliphatic nitro
compound, such as nitromethane. In this case corresponding
bis(2-ethylhexyl) N-methylphosphoramidate or tris(2-ethylhexyl)
N-methylphosphorimidate were not detected and, consequently, the
reaction did not take place. Of course, there are many other and more
efficient N-alkylation possibilities of carbazole unit. However, the
mixture of trialkyl phosphite and aromatic nitro compound was not
published and we report the procedure as a Supplementary data.
Scheme 2. 2,7-Diiodocarbazole alkylation by diethyl N-(4-tolyl)phosphoramidate (9)
or triethyl N-(4-tolyl)phosphorimidate (10) in triethyl phosphite and argon.
The 2,7-diiodocarbazole (5) and diethyl N-(4-tolyl)phosphor-
ꢀ
amidate (9) were heated in triethyl phosphite at 160 C under argon
for 5 h. We did not detect any formation of 6, therefore the tem-
ꢀ
perature was increased to 220 C for an additional 3 h. The formation
of N-ethyl-2,7-diiodocarbazole was detected (TLC) and a low yield
(
5%) of 6 was isolated by column chromatography. In a similar pro-
cedure, the phosphoramidate 9 was replaced by triethyl N-(4-tolyl)
phosphorimidate (10) and the reaction mixture was heated at 190 C
2.4. Indole alkylation
ꢀ
for 9 h. The alkylated carbazole was detected and a moderate yield
Finally, we examined the indole (13) as an example of another
nitrogen containing heterocyclic compound for the N-alkylation
procedure (Scheme 5). Similarly to carbazole above, the indole (13)
and 4-nitrotoluene (1:1.5) was mixed with tris(2-ethylhexyl)
phosphite (2.8 mol excess per 4-nitrotoluene, i.e.,1.7 mol excess per
(
22%) was isolated by column chromatography. By this way the al-
kylation ability of phosphoramidate or phosphorimidate derivatives
was proved. The higher alkylation efficiency of 10 at lower temper-
5
ature in comparison with 9 was in agreement with reported data.
ꢀ
However, the alkylation efficiency of 4-nitrotoluene was found to
be much higher than that of 10. The comparison under the same
reaction condition is shown in Scheme 3, where instead of
both components) and heated at 160 C under argon for 5 h. The
N-(2-ethylhexyl)indole (14) and unreacted indole (13) were iso-
lated in the yield of 38% and 50%, respectively, by column chro-
matography on silica gel in toluene/heptane (1:1 by vol). The
4
-nitrotoluene in the entry a (Table 1), the phosphorimidate 10 was
ꢀ
ꢀ
used. The finding, that in situ applied 4-nitrotoluene was more ef-
ficient then compound 10, supports the thought about importance of
simultaneous steps 1e3 above.
temperature increase to 190 C or longer reaction time at 160 C led
to decomposition of reaction mixture since products of decay were
observed in condenser or on TLC. Again as for carbazole, there are
many N-alkylation possibilities for the indole, but the mixture of
trialkyl phosphite and aromatic nitro compound was not the case
yet. We report the new procedure as a Supplementary data.
Scheme 3. Comparison of alkylation efficiency of 4-nitrotoluene and triethyl
N-(4-tolyl)phosphorimidate (10) under the same reaction condition.
Scheme 5. Indole alkylation with tris(2-ethylhexyl) phosphite and 4-nitrotoluene.
2
.3. Carbazole alkylation
3. Conclusion
We have found out that the mixture of aromatic nitro compound
and trialkyl phosphite can be utilized as alkylating agent for carba-
zole itself. The typical reaction is shown in Scheme 4. The carbazole
0
In summary, the reaction of 4,4 -dihalo-2-nitrobiphenyl with
the aromatic nitro compound and trialkyl phosphite results in si-
multaneous carbazole ring closure and N-alkylation, unlike the
Cadogan reaction, where just the ring closure takes place. By this
way the new efficient and simple synthesis of N-alkyl-2,7-
dihalocarbazoles was developed. Three reaction steps were sug-
gested for the synthesis in one pot experimental arrangement. The
addition of aromatic nitro compound into the reaction plays a cru-
cial role and efficient alkylating species arise in situ. The synthe-
sized phosphoramidate or phosphorimidate derivatives were
utilized just for mechanism explanation but otherwise they gave
lower yields in alkylation. As a Supplementary data, the mixture of
aromatic nitro compound and trialkyl phosphite was found to be
a possible N-alkylating agent for heterocycles, such as carbazole or
indole.
(
11) and 4-nitrotoluene (1:1.5) were mixed with tris(2-ethylhexyl)
ꢀ
phosphite (1.7 equiv) and heated at 190 C under argon for 14 h. We
used a lower phosphite excess in comparison with Table 1 because
Scheme 4. Carbazole alkylation with tris(2-ethylhexyl) phosphite and 4-nitrotoluene.

5078
D. V yꢀ prachtick yꢀ et al. / Tetrahedron 68 (2012) 5075e5080
4
4
. Experimental section
1479, 1445, 1418, 1323, 1314, 1262, 1253, 1239, 1210, 1133, 1048, 994,
ꢂ1
.
939, 888, 851, 796, 744, 588, 552, 511, 482 cm
.1. General experimental
4
.2.3. N-(2-Ethylhexyl)-2,7-diiodocarbazole (7c). Yield: 1.27
g
0
0
ꢀ
10
ꢀ
The starting 4,4 -diiodobiphenyl, 4,4 -dibromobiphenyl and the
(60%), white crystals, mp 110e111 C (lit. 110e111 C); [found: C,
45.29; H, 4.21; N, 2.61; I, 47.84. C20 N (531.2) requires C, 45.22;
H, 4.36; N, 2.64; I, 47.78%]; R (50% toluene/heptane) 0.90;
(300.1 MHz, CDCl ) 7.73 (2H, d, J 8.1 Hz, aromatic), 7.66 (2H, s, ar-
omatic), 7.48 (2H, d, J 8.1 Hz, aromatic), 3.99 (2H, dd, J 7.5, 3.6 Hz,
NeCH ),
), 1.99e1.94 (1H, m, ]CHe), 1.37e1.23 (8H, m, 4ꢁ CH
0.91e0.84 (6H, m, 2ꢁ CH ); (75.45 MHz, CDCl ) 10.9, 14.1, 23.1,
24.3, 28.5, 30.7, 39.1, 47.5 (8C, aliphatic) and 90.8 (2C), 118.3 (2C),
121.8 (4C), 128.2 (2C), 141.7 (2C) all aromatic; max(ATR) 3063, 2956,
other chemicals were purchased from Aldrich and used directly
without purification. 2-Nitrobiphenyl and tris(2-ethylhexyl) phos-
23 2
H I
f
d
H
0
7
phite were purchased from TCI. 4,4 -Dichloro-2-nitrobiphenyl,
3
0
8
0
10
4
,4 -dibromo-2-nitrobiphenyl, and 4,4 -diiodo-2-nitrobiphenyl,
were synthesized according to the published procedures. Silica
gel 60 (0.063e0.200 mm, Merck) was used for column chroma-
tography (columns 3e4ꢁ60 cm). The TLC was performed with
2
2
3
d
C
3
1
13
Silica gel 60 F254 aluminum sheets (Merck). H NMR and C NMR
n
spectra were measured in CDCl
3
, deuterated dimethylsulfoxide or
2922, 2868, 2854, 1855, 1682, 1616, 1578, 1483, 1446, 1421, 1324,
acetone with an upgraded Bruker Advance DPX-300 spectrometer
at 300.1 and 75.45 MHz, respectively, with hexamethyldisiloxane as
internal standard. FTIR spectra were measured on a PerkineElmer
Paragon 1000 PC Fourier transform infrared spectrometer by means
of diamond ATR. GCeMS measurements were performed with
a PerkineElmer gas chromatograph Auto System XL equipped with
mass spectrometer Turbo Mass. The melting points were de-
termined with a Kofler block apparatus (VEB W a€ getechnik Rapido,
1309, 1269, 1249, 1134, 1046, 994, 942, 867, 846, 820, 792, 586, 554,
ꢂ1
501, 480 cm
.
4.2.4. N-Ethyl-2,7-dibromocarbazole (7d). Yield: 0.80 g (57%), white
ꢀ
15
crystals, mp 133e134 C (lit. compound 7d was prepared without
mp report); [found: C, 47.59; H, 3.18; N, 3.89; Br, 45.22. C14
(353.05) requires C, 47.63; H, 3.14; N, 3.97; Br, 45.26%]; R
toluene/heptane) 0.84; (300.1 MHz, CDCl ) 7.83 (2H, d, J 8.4 Hz,
aromatic), 7.49 (2H, s, aromatic), 7.30 (2H, d, J 8.4 Hz, aromatic), 4.21
2H, q, J 7.2 Hz, N-CH ), 1.38 (3H, t, J 7.2 Hz, CH ); (75.45 MHz,
CDCl ) 13.8, 37.8 (2C, aliphatic) and 111.8 (2C), 119.7 (2C), 121.4 (2C),
121.6 (2C), 122.6 (2C), 140.9 (2C) all aromatic. max(ATR) 3071, 2970,
931, 2865, 1869, 1621, 1584, 1484, 1449, 1423, 1324, 1315, 1269,
H11Br N
2
f
(50%
d
H
3
Germany) and were not corrected.
(
2
3
d
C
4
.2. General synthesis for N-alkyl-2,7-dihalocarbazoles
3
(
7aem) and 2,7-dihalocarbazoles (8aem)
n
2
0
ꢂ1
The 4,4 -dihalo-2-nitrobiphenyl (0.004 mol) and 4-nitrotoluene
1230, 1131, 1055, 997, 940, 919, 842, 785, 751, 603, 588, 557 cm
.
ꢀ
(
0.006 mol) were heated at 160 C with an excess of trialkyl
phosphite (0.05 mol) under argon for 5 h (aeh, j, k) or 17 h (i, m).
After cooling the excess of trialkyl phosphite and the trialkyl
phosphate were removed under vacuum. The reaction mixture was
chromatographed (column 3ꢁ60 cm) on silica gel in toluene/hep-
4.2.5. N-(n-Butyl)-2,7-dibromocarbazole (7e). Yield: 0.96 g (63%),
white crystals, mp 113e114 C (lit. compound 7e was prepared
without mp report); [found: C, 50.41; H, 3.95; N, 3.62; Br, 41.62.
ꢀ
16
C
16
H
15Br
2
N (381.11) requires C, 50.42; H, 3.97; N, 3.68; Br, 41.93%];
(50% toluene/heptane) 0.85; (300.1 MHz, CDCl ) 7.84 (2H, d, J
8.1 Hz, aromatic), 7.49 (2H, s, aromatic), 7.30 (2H, d, J 8.1 Hz, aro-
matic), 4.14 (2H, t, J 7.2 Hz, NeCH ), 1.83e1.73 (2H, m, NeCeCH ),
1.42e1.30 (2H, m, NeCeCeCH ), 0.93 (3H, t, J 7.2 Hz, CH );
(75.45 MHz, CDCl ) 13.9, 20.6, 31.0, 43.2 (4C, aliphatic) and 112.0
(2C), 119.7 (2C), 121.3 (2C), 121.5 (2C), 122.5 (2C), 141.4 (2C) all ar-
omatic; max(ATR) 3072, 2956, 2930, 2871, 1875, 1684, 1621, 1583,
tane (1:1 by vol). The main product 7 (R
arated from the side product 8 (R
materials (7aem) were characterized by TLC, elemental analysis,
f
¼0.8e0.9) was easy sep-
R
f
d
H
3
f
¼0.5e0.6). The prepared new
2
2
1
13
melting point, H and C NMR and FTIR. The chromatographic pure
materials 7 were for melting point determination recrystallized
from methanol. The non-alkylated carbazoles 8 were identified by
2
3
d
C
3
10
means of separately prepared 2,7-diiodocarbazole (8aec), 2,7-
n
dibromocarbazole8 (8def), 2,7-dichlorocarbazole (8gei), and
7
1484, 1448, 1421, 1325, 1314, 1271, 1243, 1226, 1211, 1132, 1054, 996,
11
ꢂ1
with commercial carbazole (8jem).
955, 896, 843, 790, 732, 611, 593, 557 cm
.
4
.2.1. N-Ethyl-2,7-diiodocarbazole (7a). Yield: 0.68 g (38%), white
4.2.6. N-(2-Ethylhexyl)-2,7-dibromocarbazole (7f). Yield: 1.22 g
ꢀ
10
ꢀ
ꢀ
17
ꢀ
crystals, mp 158e160 C (lit. 158e160 C); [found: C, 37.76; H,
.41; N, 3.04; I, 56.97. C14 N (447.05) requires C, 37.61; H, 2.48;
N, 3.13; I, 56.77%]; R (50% toluene/heptane) 0.83; (300.1 MHz,
CDCl ) 7.76 (2H, s, aromatic), 7.72 (2H, d, J 6.3 Hz, aromatic), 7.50
2H, d, J 8.1 Hz, aromatic), 4.23 (2H, q, J 7.2 Hz, NeCH ), 1.39 (3H, t, J
.2 Hz, CH ); (75.45 MHz, CDCl ) 14.7, 38.7 (2C, aliphatic) and
(70%), white crystals, mp 99e100 C (lit. 99e100 C); [found: C,
55.10; H, 5.21; N, 3.17; Br, 36.60. C20 N (437.22) requires C,
54.94; H, 5.30; N, 3.20; Br, 36.55%]; R (50% toluene/heptane) 0.90;
(300.1 MHz, CDCl ) 7.85 (2H, d, J 8.4 Hz, aromatic), 7.47 (2H, s,
aromatic), 7.31 (2H, d, J 8.4 Hz, aromatic), 4.02 (2H, dd, J 7.5, 3.0 Hz,
NeCH ),
), 2.01e1.97 (1H, m, ]CHe), 1.37e1.23 (8H, m, 4ꢁ CH
0.91e0.83 (6H, m, 2ꢁ CH ); (75.45 MHz, CDCl ) 11.1, 14.2, 23.2,
24.5, 28.7, 31.0, 39.3, 47.8 (8C, aliphatic) and 112.5 (2C), 119.8 (2C),
121.4 (2C), 121.6 (2C), 122.7 (2C), 142.0 (2C) all aromatic; max(ATR)
2
H I
11 2
H23Br
2
f
d
H
f
3
d
H
3
(
7
2
3
d
C
3
2
2
91.8 (2C), 118.7 (2C), 122.8 (2C), 122.9 (2C), 129.2 (2C), 141.2 (2C) all
3
d
C
3
aromatic; nmax(ATR): 3060, 2968, 2925, 2864, 1876, 1734, 1689,
1615, 1579, 1482, 1446, 1419, 1336, 1315, 1230, 1135, 1052, 994, 939,
n
ꢂ1
9
08, 846, 800, 791, 582, 553, 499, 458 cm . FTIR spectra of car-
3074, 2958, 2924, 2858, 1856, 1688, 1621, 1584, 1483, 1450, 1425,
14
bazole derivatives 7aem were in agreement with published data.
1327, 1309, 1270, 1247, 1130, 1053, 997, 946, 874, 845, 821, 795, 593,
ꢂ1
558, 479 cm
.
4
.2.2. N-(n-Butyl)-2,7-diiodocarbazole (7b). Yield: 0.84 g (44%),
ꢀ
white crystals, mp 140e142 C; [found: C, 40.22; H, 3.15; N, 3.04; I,
4.2.7. N-Ethyl-2,7-dichlorocarbazole (7g). Yield: 0.78 g (74%), white
ꢀ
5
3.51. C16
H
15
2
I N (475.11) requires C, 40.45; H, 3.18; N, 2.95; I,
crystals, mp 136e137 C; [found: C, 63.46; H, 4.18; N, 5.22; Cl, 26.73.
5
3.42%]; R
f
(50% toluene/heptane) 0.87; (300.1 MHz, CDCl ) 7.75
d
H
3
C
14
H
11Cl
2
N (264.15) requires C, 63.66; H, 4.20; N, 5.30; Cl, 26.84%];
(50% toluene/heptane) 0.85; (300.1 MHz, CDCl ) 7.86 (2H, d, J
8.7 Hz, aromatic), 7.32 (2H, s, aromatic), 7.15 (2H, d, J 8.4 Hz, aro-
matic), 4.20 (2H, q, J 7.2 Hz, NeCH ), 1.37 (3H, t, J 7.2 Hz, CH );
(75.45 MHz, CDCl ) 13.7, 37.9 (2C, aliphatic) and 108.9 (2C), 119.9
(2C), 121.1 (2C), 121.2 (2C), 131.8 (2C), 140.8 (2C) all aromatic;
max(ATR) 3061, 2963, 2928, 2867, 1862, 1672, 1626, 1591, 1485,
(
2H, s, aromatic), 7.70 (2H, d, J 8.4 Hz, aromatic), 7.50 (2H, d, J 8.1 Hz,
aromatic), 4.14 (2H, t, J 7.2 Hz, NeCH ), 1.83e1.73 (2H, m,
NeCeCH ), 1.42e1.29 (2H, m, NeCeCeCH ), 0.95 (3H, t, J 6.5 Hz,
CH ); (75.45 MHz, CDCl ) 13.9, 20.6, 30.9, 43.1 (4C, aliphatic) and
0.8 (2C), 118.1 (2C), 121.3 (2C), 121.8 (2C), 128.2 (2C), 141.3 (2C) all
aromatic; max(ATR) 3066, 2954, 2927, 2868, 1882, 1694, 1614, 1578,
R
f
d
H
3
2
2
2
2
3
d
C
3
d
C
3
3
9
n
n

D. V yꢀ prachtick yꢀ et al. / Tetrahedron 68 (2012) 5075e5080
5079
1
449, 1427, 1327, 1317, 1270, 1222, 1130, 1065, 1000, 929, 838, 785,
1323, 1244, 1217, 1203, 1152, 1120, 1062, 1001, 922, 846, 746, 719,
ꢂ1
ꢂ1
748, 614, 598, 563 cm
.
616, 564, 528 cm
.
4
.2.8. N-(n-Butyl)-2,7-dichlorocarbazole (7h). Yield: 0.85 g (73%),
4.3. Alkylation of 2,7-diiodocarbazole (5) with diethyl
N-(4-tolyl)phosphoramidate (9)
ꢀ
white crystals, mp 102e103 C; [found: C, 65.83; H, 5.13; N, 4.76; Cl,
2
3.96. C16
H15Cl
2
N (292.20) requires C, 65.77; H, 5.17; N, 4.79; Cl,
2
4.27%]; R
f
(50% toluene/heptane) 0.90; (300.1 MHz, CDCl ) 7.87
d
H
3
The 2,7-diiodocarbazole (5, 0.419 g, 0.001 mol) and diethyl N-(4-
tolyl)phosphoramidate (9, 0.365 g, 0.0015 mol) were heated in
triethyl phosphite (10 mL) at 160 C in argon for 5 h. We did not
(
2H, d, J 8.4 Hz, aromatic), 7.32 (2H, s, aromatic), 7.16 (2H, d, J 8.4 Hz,
aromatic), 4.14 (2H, t, J 7.2 Hz, NeCH ), 1.83e1.73 (2H, m,
NeCeCH ), 1.42e1.30 (2H, m, NeCeCeCH ), 0.93 (3H, t, J 7.2 Hz,
CH ). (75.45 MHz, CDCl ) 13.9, 20.6, 30.9, 43.2 (4C, aliphatic) and
09.1 (2C), 119.9 (2C), 120.9 (2C), 121.1 (2C), 131.8 (2C), 141.3 (2C) all
ꢀ
2
2
2
detect any formation of 6, so the temperature was increased
ꢀ
3
d
C
3
to 220 C for additional 3 h. The formation of N-ethyl-2,7-
1
diiodocarbazole (6) was detected (TLC) and low yield of 6
(0.022 g, 5%) was isolated by column chromatography on silica gel
in toluene/heptane (1:1 by vol) from reaction mixture. The pre-
pared 6 was characterized by TLC, melting point, elemental anal-
aromatic;
n
max(ATR) 3078, 2959, 2933, 2873, 1872, 1681, 1626, 1589,
1488, 1453, 1428, 1327, 1316, 1270, 1241, 1226, 1213, 1132, 1065, 999,
ꢂ1
9
61, 905, 843, 792, 735, 602, 592, 562 cm
.
1
ysis, and H NMR as N-ethyl-2,7-diiodocarbazole. All analytic
4
.2.9. N-(2-Ethylhexyl)-2,7-dichlorocarbazole (7i). Yield: 0.86
g
procedures confirmed the identity of 6 with compound 7a (ana-
lytical data see above). The diethyl N-(4-tolyl)phosphoramidate (9,
ꢀ
7
ꢀ
(
62%), white crystals, mp 68e69 C (lit. 68e69 C); [found: C,
6
6
9.20; H, 6.70; N, 3.99; Cl, 20.12. C20
8.97; H, 6.66; N, 4.02; Cl, 20.36%]; R
(300.1 MHz, CDCl ) 7.87 (2H, d, J 8.4 Hz, aromatic), 7.29 (2H, s,
aromatic), 7.16 (2H, d, J 8.4 Hz, aromatic), 3.99 (2H, dd, J 7.4, 2.6 Hz,
NeCH ),
) 10.9, 14.1, 23.1,
4.4, 28.6, 30.9, 39.2, 47.7 (8C, aliphatic) and 109.3 (2C), 119.8 (2C),
20.9 (2C), 121.1 (2C), 131.7 (2C), 141.8 (2C) all aromatic; max(ATR)
075, 2960, 2925, 2859, 1858, 1681, 1625, 1589, 1487, 1454, 1429,
H
23Cl
2
N (348.31) requires C,
C
11
H
18NO
3
P¼243.24) was synthesized from 4-nitrotoluene and
f
(50% toluene/heptane) 0.90;
triethyl phosphite according to recently published procedure by
Beifuss et al. as a yellow crystalline solid (mp 94e95 C, lit.
95 C); [found: C, 54.49; H, 7.52; N, 5.71. C11
requires C, 54.32; H, 7.46; N, 5.76%].
12
ꢀ
4d
d
H
3
ꢀ
3
H18NO P (243.24)
2
), 2.02e1.94 (1H, m, ]CHe), 1.41e1.18 (8H, m, 4ꢁ CH
2
0.91e0.82 (6H, m, 2ꢁ CH ); (75.45 MHz, CDCl
2
3
d
C
3
4.4. Alkylation of 2,7-diiodocarbazole (5) with triethyl
N-(4-tolyl)phosphorimidate (10)
1
3
n
1
5
328, 1310, 1269, 1246, 1129, 1064, 999, 949, 882, 845, 822, 797, 601,
63, 529 cm
The 2,7-diiodocarbazole (5, 0.419 g, 0.001 mol) and triethyl N-
(4-tolyl)-phosphorimidate (10, 0.407 g, 0.0015 mol) were heated in
triethyl phosphite (10 mL) at 190 C in argon for 9 h. The formation
ꢂ1
.
ꢀ
4
6
C
.2.10. N-Ethylcarbazole (7j). Yield: 0.63 g (81%), white crystals, mp
of N-ethyl-2,7-diiodocarbazole (6) was detected (TLC) and moder-
ate yield of 6 (0.098 g, 22%) was isolated by column chromatogra-
phy on silica gel in toluene/heptane (1:1 by vol) from reaction
mixture. The prepared 6 was characterized by TLC, melting point,
elemental analysis, and H NMR as N-ethyl-2,7-diiodocarbazole. All
analytic procedures confirmed the identity of 6 with compound 7a
(analytical data see above). The triethyl N-(4-tolyl)phosphor-
ꢀ
18
ꢀ
5e66 C (lit. 65e66 C); [found: C, 85.95; H, 6.85; N, 7.06.
13N (195.26) requires C, 86.12; H, 6.71; N, 7.17%]; R (50% tol-
(300.1 MHz, CDCl ) 8.07 (2H, d, J 7.8 Hz,
aromatic), 7.46e7.35 (4H, m, aromatic), 7.20 (2H, t, J 8.0 Hz, aro-
matic), 4.32 (2H q, J 7.2 Hz, NeCH ), 1.38 (3H, t, J 7.2 Hz, CH );
) 13.8, 37.5 (2C, aliphatic) and 108.5 (2C), 118.8
2C), 120.4 (2C), 122.9 (2C), 125.6 (2C), 139.9 (2C) all aromatic;
max(ATR) 3049, 2978, 2931, 2890, 1891, 1780, 1685, 1625, 1594,
482, 1466, 1451, 1325, 1280, 1228, 1151, 1129, 1082, 1019, 997, 937,
14
H
f
uene/heptane) 0.76;
d
H
3
1
2
3
d
C
(
(
75.45 MHz, CDCl
3
imidate (10, C13
H
22NO
3
P¼271.29) was prepared by a thermal de-
n
oxygenation reaction from 4-nitrotoluene and triethyl phosphite
13
1
according to procedure described by Sundberg et al. as a yellow
ꢂ1
ꢀ
13
ꢀ
8
87, 783, 750, 721, 615, 560, 528 cm
.
oil (bp 111e113 C/67 Pa, lit. 98e101 C/27 Pa); [found: C, 57.61; H,
.25; N, 5.11. C13 P (271.13) requires C, 57.55; H, 8.17; N,
5.16%].
8
H22NO
3
4.2.11. N-(n-Butyl)carbazole (7k). Yield: 0.73 g (82%), white crys-
ꢀ
19
ꢀ
tals, mp 57e58 C (lit. 57e59 C); [found: C, 86.08; H, 7.92; N,
.40. C16 17N (223.31) requires C, 86.05; H, 7.67; N, 6.27%]; R (50%
toluene/heptane) 0.87; (300.1 MHz, CDCl ) 8.07 (2H, d, J 7.8 Hz,
aromatic), 7.46e7.36 (4H, m, aromatic), 7.20 (2H, t, J 7.4 Hz, aro-
matic), 4.26 (2H, t, J 7.2 Hz, NeCH ), 1.86e1.79 (2H, m, NeCeCH ),
.43e1.30 (2H, m, NeCeCeCH ), 0.91 (3H, t, J 7.5 Hz, CH );
75.45 MHz, CDCl ) 13.9, 20.6, 31.2, 42.8 (4C, aliphatic) and 108.7
2C), 118.7 (2C), 120.4 (2C), 122.8 (2C), 125.6 (2C), 140.5 (2C) all
max(ATR) 3054, 2952, 2929, 2869, 1919, 1882, 1762, 1686,
625, 1592, 1482, 1462, 1449, 1348, 1325, 1261, 1240, 1212, 1151,
6
H
f
4.5. Synthesis of N-(2-ethylhexyl)carbazole (12)
d
H
3
The carbazole (11, 1.67 g, 0.01 mol) and 4-nitrotoluene (2.06 g,
2
2
0.015 mol) was mixed with tris(2-ethylhexyl)phosphite (17.8 g,
ꢀ
1
(
(
2
3
d
C
0.0425 mol) and heated at 190 C in argon for 14 h. When cooled
3
the reaction mixture was chromatographed on silica gel in toluene/
heptane (1:1 by vol). The N-(2-ethylhexyl)carbazole (12, R
f
¼0.87)
aromatic;
1
n
was easy separated from unreacted carbazole (11, R
f
¼0.35). The
corresponding fractions were collected, evaporated and dried to
constant weight in vacuum. Yield: 1.54 g (55%) of 12 (colorless oil)
and 0.62 g (37%) of 11 (white crystals); [found for 12: C, 86.14; H,
ꢂ1
1119, 1017, 999, 958, 876, 770, 742, 722, 615, 558, 528 cm
.
4
.2.12. N-(2-Ethylhexyl)carbazole (7m). Yield: 0.54 g (48%), color-
25N (279.42) requires
(50% toluene/heptane) 0.87;
) 8.10 (2H, d, J 7.8 Hz, aromatic), 7.49 (2H, d, J
.4 Hz, aromatic), 7.41 (2H, t, J 8.1 Hz, aromatic), 7.16 (2H, t, J 7.8 Hz,
aromatic), 4.24 (2H, d, J 7.5 Hz, NeCH ), 2.08e2.00 (1H, m, ]CHe),
.40e1.15 (8H, m, 4ꢁ CH ), 0.88 (3H, t, J 7.5 Hz, CH ), 0.79 (3H, t, J
.2 Hz, CH ); (75.45 MHz, acetone-d ) 11.2, 14.2, 23.7, 24.9, 29.4,
1.6, 40.1, 47.7 (8C, aliphatic) and 110.1 (2C), 119.5 (2C), 120.9 (2C),
23.5 (2C), 126.4 (2C), 141.7 (2C) all aromatic; max(ATR): 3054,
956, 2926, 2870, 1878, 1760, 1626, 1597, 1483, 1461, 1450, 1343,
9.08; N, 5.07. C20
H and C NMR (acetone-d ) and FTIR (ATR) confirmed the struc-
ture of 12 and were found to be the same as for 7m.
4.6. Synthesis of N-(2-ethylhexyl)indole (14)
H
25N (279.42) requires C, 85.97; H, 9.02; N, 5.01%].
1
13
less oil; [found: C, 85.81; H, 9.35; N, 5.01. C20
C, 85.97; H, 9.02; N, 5.01%]; R
300.1 MHz, acetone-d
H
6
f
d
H
(
8
6
2
1
7
3
1
2
3
The indole (13, 1.18 g, 0.01 mol) and 4-nitrotoluene (2.06 g,
0.015 mol) was mixed with tris(2-ethylhexyl)phosphite (17.8 g,
0.0425 mol) and heated at 160 C in argon for 5 h. When cooled the
reaction mixture was chromatographed on silica gel in toluene/
3
d
C
6
ꢀ
n
2
heptane (1:1 by vol). The N-(2-ethylhexyl)indole (14, R
f
¼0.77) was

5080
D. V yꢀ prachtick yꢀ et al. / Tetrahedron 68 (2012) 5075e5080
easy separated from unreacted 4-nitrotoluene (R
13, R
¼0.30). The corresponding fractions were collected, evapo-
rated and vacuum dried to constant weight. Yield: 0.88 g (38%) of 14
yellow oil) and 0.60 g (50%) of 13 (white crystals); [found for 14: C,
3.81; H, 10.33; N, 6.11. C16 23N (229.36) requires C, 83.79; H, 10.11;
N, 6.11%]; (300.1 MHz, acetone-d , 14) 7.52 (1H, d, J 8.4 Hz, aro-
f
¼0.45) and indole
References and notes
(
f
1
. (a) Wang, Y.-S.; He, H.-P.; Shen, Y.-M.; Hong, X.; Hao, X.-J. J. Nat. Prod. 2003, 66,
16e418; (b) Chakravarty, A. K.; Sarkar, T.; Masuda, K.; Shiojima, K. Phyto-
chemistry 1999, 50, 1263e1266.
2. (a) Kimoto, A.; Cho, J.-S.; Higuchi, M.; Yamamoto, K. Macromolecules 2004, 37,
531e5537; (b) Boudreault, P.-L. T.; Blouin, N.; Leclerc, M. Adv. Polym. Sci. 2008,
12, 99e124; (c) Iraqi, A.; Wataru, I. Chem. Mater. 2004, 16, 442e448.
4
(
8
H
5
2
d
H
6
matic), 7.36 (1H, d, J 8.4 Hz, aromatic), 7.20 (1H, d, J 3.3 Hz, aro-
matic), 7.10 (1H, t, J 7.5 Hz, aromatic), 6.98 (1H, t, J 7.4 Hz, aromatic),
3
. (a) Cimrov ꢀa , V.; Kmínek, I.; V yꢀ prachtick yꢀ , D. Macromol. Symp. 2010, 295, 65e70;
(b) Boudreault, P.-L. T.; Beaupr eꢀ , S.; Leclerc, M. Polym. Chem. 2010, 1, 127e136;
(
2
c) V yꢀ prachtick yꢀ , D.; Cimrov aꢀ , V.; Kmínek, I.; Pavla ꢁc kov ꢀa , P. Macromol. Symp.
010, 295, 94e99.
6
2
.40 (1H, d, J 3.0 Hz, aromatic), 4.03 (2H, d, J 7.5 Hz, NeCH
.00e1.85 (1H, m, ]CHe), 1.32e1.20 (8H, m, 4ꢁ CH ), 0.88e0.79
); (75.45 MHz, acetone-d , 14) 10.8, 14.2, 23.6,
4.5, 29.2, 31.3, 40.8, 50.6 (8C, aliphatic) and 101.3, 110.4, 119.7,
max(ATR, 14) 3052,
2
),
2
4
. (a) Cadogan, J. I. G.; Cameron-Wood, M.; Mackie, R. K.; Searle, R. J. G. J. Chem.
Soc. 1965, 4831e4837; (b) Cadogan, J. I. G.; Cooper, A. J. Chem. Soc. B 1969,
883e885; (c) Cadogan, J. I. G.; Todd, M. J. J. Chem. Soc. C 1969, 2808e2813; (d)
Cadogan, J. I. G.; Sears, D. J.; Smith, D. M.; Todd, M. J. J. Chem. Soc. C 1969,
(
2
6H, m, 2ꢁ CH
3
d
C
6
121.4, 121.8, 129.4, 129.6, 137.2 (8C, aromatic);
n
2813e2819.
2
956, 2926, 2870, 1611, 1511, 1483, 1462, 1332, 1312, 1249, 1190,
5
6
. (a) Tsunashima, Y.; Kuroki, M. J. Heterocycl. Chem. 1981, 18, 315e318; (b) Puskas,
I.; Fields, E. K. J. Org. Chem. 1968, 33, 4237e4242.
. Freeman, A. W.; Urvoy, M.; Criswell, M. E. J. Org. Chem. 2005, 70, 5014e5019.
ꢂ1
1153, 1112, 1087, 1012, 882, 761, 736, 713, 588, 573, 464 cm
.
7
. Morin, J. F.; Leclerc, M. Macromolecules 2001, 34, 4680e4682.
. Dierschke, F.; Grimsdale, A. C.; M u€ llen, K. Synthesis 2003, 16, 2470e2472.
9. Pan, X.; Liu, S.; Chan, H. S. O.; Ng, S.-C. Macromolecules 2005, 38, 7629e7635.
0. V yꢀ prachtick yꢀ , D.; Kmínek, I.; Pavla ꢁc kov aꢀ , P.; Cimrov ꢀa , V. Synthesis 2011, 9,
472e1476.
1. Carbazole p.a. was purchased from Lachema Brno, Czech Republic.
12. Haggam, R.; Conrad, J.; Beifuss, U. Tetrahedron Lett. 2009, 50, 6627e6630.
3. Sundberg, R. J.; Das, B. P.; Smith, R. H., Jr. J. Am. Chem. Soc. 1969, 91, 658e668.
4. Bree, A.; Zwarich, R. J. Chem. Phys. 1968, 49, 3344e3355.
5. Liu, X.; Sun, Y.; Zhang, Y.; Miao, F.; Wang, G.; Zhao, H.; Yu, X.; Liu, H.; Wong,
W.-Y. Org. Biomol. Chem. 2011, 9, 3615e3618.
8
Acknowledgements
1
1
The authors thank the Ministry of Education, Youth and Sports
of the Czech Republic (grant No. 1M06031) and the Grant Agency of
the Czech Republic (grant No. P106/12/0827) for financial support.
1
1
1
1
1
6. Gao, P.; Feng, X.; Yang, X.; Enkelmann, V.; Baumgarten, M.; M u€ llen, K. J. Org.
Chem. 2008, 73, 9207e9213.
Supplementary data
1
7. Qiu, S.; Liu, L.; Wang, B.; Shen, F.; Zhang, W.; Li, M.; Ma, Y. Macromolecules 2005,
38, 6782e6788.
1H and 13C NMR spectra of 7aem and 14. Supplementary data
related to this article can be found online at doi:10.1016/
j.tet.2012.04.044.
18. Kricka, L. J.; Ledwith, A. J. Chem. Soc., Perkin Trans. 1 1972, 2292e2293.
19. Bogdal, D.; Pielichowski, J.; Jaskot, K. Synth. Commun. 1997, 27, 1553e1560.