Synthesis of 3-acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole

Article abstract of DOI:10.1007/s11164-010-0148-z

3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole was prepared through successive o-methyl benzoylation and acetylation of N-ethylcarbazole in one pot. The overall yield was 85.6% and the structure was confirmed by ¹H-NMR and ¹³C-NMR. A

Full text of DOI:10.1007/s11164-010-0148-z

Res Chem Intermed (2010) 36:383–387
DOI 10.1007/s11164-010-0148-z
Synthesis of 3-acetyl-6-(o-methyl benzoyl)-
N-ethylcarbazole
•
Ling Gong Chao Qian Xinzhi Chen
•
Received: 4 September 2009 / Accepted: 13 January 2010 / Published online: 11 June 2010
Ó Springer Science+Business Media B.V. 2010
Abstract 3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole was prepared through
successive o-methyl benzoylation and acetylation of N-ethylcarbazole in one pot.
1
The overall yield was 85.6% and the structure was confirmed by H-NMR and
13C-NMR. A preliminary investigation had also been carried out on the mechanism
of the o-methyl benzoylation of N-ethylcarbazole.
Keywords 3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole ꢀ Acylation ꢀ
Aluminum chloride
Introduction
Carbazole and its derivatives had been widely used in optical materials for their
huge conjugated systems and active intramolecular electron transfer [1, 2].
Recently, with the further research of two-photon chemistry, more and more
people focused their research on the synthesis of new carbazole derivatives with
longer conjugated chain, which was in favor of larger two-photon absorption cross-
section and stronger two-photon property [3].
Herein, 3-acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole, a new carbazole deriv-
ative with special D–p–D structure, was synthesized through two successive
different acylation of N-ethylcarbazole, as sketched in Scheme 1. In this product,
the N atom of carbazole was linked with an alkyl chain to increase the electron
L. Gong ꢀ C. Qian (&) ꢀ X. Chen
Department of Chemical Engineering, Zhejiang University,
Hangzhou 310027, People’s Republic of China
e-mail: supmoney@163.com
L. Gong
Engineering Department, ShanghaiChem Engineering Incorporation,
Shanghai 200235, People’s Republic of China
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L. Gong et al.
O
O
AlCl3
+
Cl
ClCH2CH2Cl
N
N
O
O
CH3COCl/AlCl3
ClCH2CH2Cl
N
Scheme 1 The synthetic route of 3-acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole
donating ability of the conjugated system, and conjugated acyl groups were
introduced to carbazole to extend the conjugated chain, thus, the two-photon
absorption cross-section and the two-photon property were further enlarged.
The two different groups introduced to N-ethylcarbazole by two successive
acylation were o-methyl benzoyl and acetyl, so the control of the o-methyl
benzoylation to monoacyl substitution, which was frequently accompanied by
diacylation (as sketched in Scheme 2), was crucial for the successful synthesis of
product. To synthesize similar compounds, the purification of the product by
column chromatography on silica gel was always needed [4]. In this paper, we
found that, surprisingly, the dosage of catalyst aluminum chloride could change the
distribution of the products to a large extent.
According to the mechanism of Friedel–Crafts acylation [5], the complex
comprised of catalyst aluminum chloride and the acylation product must be broken
down by the addition of water after the reaction. And the aluminum chloride in the
formed complex could no longer catalyze acylation. So, in acylation reactions,
theoretically, the dosage of aluminum chloride should be at least equimolar to the
raw material, and, actually, it was 10–50% in excess of the equimolar dosage in
many cases [6, 7].
However, in our case, there was no need to use an equimolar catalyst dosage
to N-ethylcarbazole to maintain high conversion in the o-methyl benzoylation.
The results showed that the conversion could reach more than 90% at 0–5 °C,
O
O
O
AlCl3
+
2
Cl
ClCH2CH2Cl
N
N
Scheme 2 The subsidiary reaction of the 3-acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole synthesis
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Synthesis of 3-acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole
385
O
O
AlCl3
Cl
AlCl3
+
Cl
O
H
O
C+
N
-
+
AlCl4
+
N
-
AlCl 4
O
AlCl3
O
Partial
Dissociation
-HCl
AlCl3
+
N
N
Recycling
Fig. 1 The mechanism of the o-methyl benzoylation of N-ethylcarbazole
even when the molar ratio between aluminum chloride and N-ethylcarbazole was
only 0.7. It was demonstrated that part of the complex-formed forehead was
dissociated, and the aluminum chloride that departed from the complex could be
reused in the acylation catalysis. Based on the findings, we supposed the
mechanism of the o-methyl benzoylation of N-ethylcarbazole as shown in Fig. 1.
The catalyst aluminum chloride and o-methyl benzoyl chloride formed a complex
to weaken the C–Cl bond, and then formed o-methyl benzoyl carbocation, which
attacked N-ethylcarbazole to form aromatic carbocation. Then, a molecule of HCl
was eliminated from the aromatic carbocation to form a complex comprised of
aluminum chloride and the acylation product. The complex could be partially
dissociated to the aluminum chloride, which formed a new complex with
another molecule of o-methyl benzoyl chloride and repeated the process
described above.
Furthermore, when the dosage of aluminum chloride was less equimolar than that
of N-ethylcarbazole, the diacylation was, to a large extent, restrained, which meant
that the o-methyl benzoylation reaction was successfully controlled in the monoacyl
substitution stage. In other words, the aluminum chloride released from the partial
dissociation of the complex made it unnecessary to use a larger catalyst dosage to
ensure the complete conversion of N-ethylcarbazole and, as a consequence, the
diacylation was avoided.
For the second step of two successive acylations progressed in one pot, the
released aluminum chloride in o-methyl benzoylation could be used in a subsequent
acetylation, and an additional 0.5 equimolar to the N-ethylcarbazole produced the
acetylation high yield.
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Experimental
All reagents were commercially obtained without further purification. The melting
point was recorded on a WSR-I capillary melting point apparatus and was
1
uncorrected. H-NMR and 13C-NMR data were recorded on a Bruker 400 MHz
spectrometer operating near 400 (1H) or 100 (13C) MHz in CDCl3 solutions and
TMS was used as the internal standard.
To a well-stirred reaction vessel, which was kept in an ice water bath to
maintain a temperature of 0–5 °C, was added aluminum chloride (4.6 g,
0.035 mol), N-ethylcarbazole (9.75 g, 0.05 mol) and dichloroethane (65 mL). To
the content, the solution of o-methyl benzoyl chloride (6.5 mL, 0.05 mol) and
dichloroethane (15 mL) was added dropwise over 0.5 h. Upon completion of the
addition, the mixture was kept at 0–5 °C for an additional 0.5 h. Then, the ice
water bath was removed and warmed slowly to room temperature. A mixture of
aluminum chloride (3.4 g, 0.025 mol) and acetyl chloride (4.5 mL, 0.06 mol) was
added and the content was kept at this temperature for another 0.5 h. Then, the
mixture was poured into water. After the phase separation, the organic layer was
successively washed with saturated sodium carbonate solution and water to
neutralization and dried over Na2SO4. Then, the solvent was completely evaporated
under reduced pressure and the residue was extracted with acetone (3 9 20 mL).
The combined acetone solution was cooled in the refrigerator to maintain a
temperature of 0 °C and kept for 12 h and, thereupon, 3-acetyl-6-(o-methyl
benzoyl)-N-ethylcarbazole was crystallized as a white solid (15.2 g, 85.6% yield),
mp. 162.1–163.2 °C.
3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole: 1H-NMR (400 MHz, CDCl3) d
(ppm): 1.46–1.50 (t, 3H, –CH2–CH3), 2.35 (s, 3H, –CH3), 2.70 (s, 3H, –CO–CH3),
4.41–4.43 (q, 2H, –CH2–), 7.29–7.48 (m, 6H, Ar–H), 8.09–8.11 (m, 1H, Ar–H),
8.14–8.17 (m, 1H, Ar–H), 8.54–8.55 (m, 1H, Ar–H), 8.68–8.69 (m, 1H, Ar–H).
13C-NMR (100 MHz, CDCl3) d (ppm): 13.81 (–CH2–CH3), 19.83 (–CH3), 26.69
(–CO–CH3), 38.16 (–CH2–), 108.69 (–Ar), 108.82 (–Ar), 122.08 (–Ar), 122.90
(–Ar), 122.93 (–Ar), 124.21 (–Ar), 125.30 (–Ar), 127.07 (–Ar), 127.97 (–Ar),
128.63 (–Ar), 129.71 (–Ar), 129.83 (–Ar), 129.93 (–Ar), 130.89 (–Ar), 136.16
(–Ar), 139.48 (–Ar), 143.37 (–Ar), 143.53 (–Ar), 197.50 (Ar–CO–Ar), 198.17
(–CO–CH3).
Conclusion
3-Acetyl-6-(o-methyl benzoyl)-N-ethylcarbazole was prepared in 85.6% yield
through two successive different acylations of N-ethylcarbazole. In the o-methyl
benzoylation of N-ethylcarbazole, less than N-ethylcarbazole molar dosage of
aluminum chloride was enough to obtain high conversion, and which was effective
to restrain the multi-acylation. The total molar dosage of aluminum chloride of two
successive acylations was reduced to 1.2 times that of N-ethylcarbazole for the
recycling of aluminum chloride in o-methyl benzoylation and the two successive
acylations in one pot.
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Acknowledgments We greatly acknowledge the generous financial support by grants from the National
Natural Science Foundation of China (No. 20776127), the National Key Technology R&D Program (No.
2007BAI34B07), and the Zhejiang Province Science and Technology Program (No. 2008C01006-1).
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