An efficient ultrasound-assisted synthesis of n-alkyl derivatives of carbazole, indole, and phenothiazine

Article abstract of DOI:10.1002/jhet.1652

Heterocyclic compounds bearing an acidic hydrogen atom attached to nitrogen such as carbazole, indole, and phenothiazine can be efficiently alkylated in DMSO or N,N-DMF under ultrasonic irradiation in the presence of potassium hydroxide as a base. In almost all cases, a dramatic reduction of the reaction time results and a clear yield increase accompanied by an improved quality of the products occurs.

Full text of DOI:10.1002/jhet.1652

May 2014
An Efficient Ultrasound-Assisted Synthesis of N-Alkyl Derivatives of
683
Carbazole, Indole, and Phenothiazine
Sanhu Zhao,* Jin Kang, Yuting Du, Jingyan Kang, Xiaoni Zhao, Yinfeng Xu,
Ruixi Chen, Qianqian Wang, and Xitao Shi
Department of Chemistry, Xinzhou Teachers University, Xinzhou 034000, China
*
E-mail: sanhuzhao@yahoo.cn
Additional Supporting Information may be found in the online version of this article.
Received December 21, 2011
DOI 10.1002/jhet.1652
Published online 2 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
S
S
+
HX
R
X
+
KOH
DMSO or DMF
N
R
N
H
Heterocyclic compounds bearing an acidic hydrogen atom attached to nitrogen
such as carbazole, indole, and phenothiazine can be efficiently alkylated in DMSO or
N,N-DMF under ultrasonic irradiation in the presence of potassium hydroxide as a
base. In almost all cases, a dramatic reduction of the reaction time results and a clear yield
increase accompanied by an improved quality of the products occurs.
J. Heterocyclic Chem., 51, 683 (2014).
INTRODUCTION
decades [14]; compared with traditional methods, the pro-
cedure is more convenient. A large number of organic
reactions can be carried out in higher yield, shorter reaction
time, or milder conditions under ultrasonic irradiation.
Because of the absence of reported ultrasonic-assisted N-
alkylation of nitrogen heterocycles and our general interest
in the development of clean chemical processes, herein, we
wish to report an improved procedure for the N-alkylation
of carbazole, indole, and phenothiazine. Under ultrasound
irradiation, a variety of N-alkyl derivatives of carbazole,
indole, and phenothiazine were prepared with mild reaction
conditions, short reaction time, and moderate to high yields
(Scheme 1).
Over the course of the last decades, N-heterocyclic com-
pounds containing carbazole, indole, and phenothiazine
units have gained much attention for their wide-ranging impli-
cations in chemistry, biology, and materials science [1]. N-
alkylcarbazole, N-alkylindole, and N-alkylphenothiazine are
the main intermediates used in these fields. Despite their
versatility, available routes for their synthesis are limited.
One of the most practical and widely used routes for the
synthesis of these compounds is direct alkylation of carbazole,
indole, or phenothiazine with an alkylation agent. They are
generally accomplished by the treatment of these compounds
with an appropriate base such as KOH [2], NaOH [3], NaH [4],
and K2CO3 [5], followed by reaction of the resulting salt with
an alkylation agent in various solvents, such as DMSO [6],
DMF [7], THF [8], and HMPT (Hexamethyl phosphoryl tria-
mide) [9], and others. In an early report, Guida found that the
N-alkylation of heterocyclic compounds can be accomplished
in diethyl ether via a phase-transfer process in which 18-
crown-6 is used as the catalyst and potassium tert- butoxide is
used as the base [10]. Recently, Hayat et al. reported on the
N-alkylation of nitrogen heterocycles with alkyl halide using
CsF/Celite in acetonitrile [11]. However, some of these meth-
ods are limited by low yields or long reaction time. Therefore,
the development of a mild and efficient method of N-alkylation
of heterocyclic compounds bearing an acidic hydrogen atom at-
tached to nitrogen is still a major challenge in organic synthesis.
Most recently, Le [12] and Jorapur [13] demonstrated N-alkyl-
ation of heterocyclic compounds in ionic liquid, respectively;
some excellent results were obtained; however, the expensive
price and inconvenience of ionic liquids may become the big-
gest obstacle to its wide application.
RESULTS AND DISCUSSION
Ultrasound-accelerated chemical reactions are well
known and proceed via the formation and adiabatic col-
lapse of the transient cavitation bubbles [14]. In previous
studies, we found that the ultrasound can accelerate the
Zincke reaction [16]. As a continuation of our research
interest in developing synthetic protocols using ultrasound
irradiation, a laboratory ultrasonic cleaning bath was used
for the N-alkylation of heterocyclic compounds bearing
an acidic hydrogen atom attached to nitrogen. In a recent
report [17], Qin developed a simple approach to synthesize
N-ethylcarbazole by using dipolar aprotic solvent DMF as
reaction medium, and using conventional magnetic stir-
ring, the reaction of carbazole with bromoethane gave the
desired product in 92.4% yield after 10 h. Although the
aforementioned method provided excellent yield, the reac-
tion time is indeed long. Thus, to shorten the reaction time
and to evaluate the effect of ultrasonic irradiation, the reac-
tion of carbazole with bromoethane in DMF with KOH as
a base was selected as a model reaction under ultrasound
Ultrasound irradiation has been considered as a clean
and useful protocol in organic synthesis in the last three
© 2013 HeteroCorporation

684
S. Zhao, J. Kang, Y. Du, J. Kang, X. Zhao, Y. Xu, R. Chen, Q. Wang, and X. Shi
Vol 51
Scheme 1
S
S
+
HX
R
X
+
KOH
DMSO or DMF
N
R
N
H
R = C2H5, C4H9, C10H19, CH2CH2CH2Br, CH2CH2CH2CH2Br, CH2CH2OH,
CH2C6H5, CH2CH=CH2, CH2CH(CH3)2, C(CH3)3
X = Br,Cl
irradiation conditions (Table 1). Initially, the effect of
ultrasonic power was investigated. To our surprise, only
after 6 min, the excellent product yield 98% was obtained
with the ultrasonic power 90 W, irradiation frequency
40 kHz, and the reaction temperature 35ꢀC (Table 1, entry 4);
it is apparent that the ultrasound can accelerate the
reaction significantly. To search the better reaction condi-
tions and because the nucleophilic substitution reactions
are strongly dependent on the polarity of the reaction
medium, several polar solvents such as DMSO, PEG-400,
THF, H2O, and three ionic liquids [N-ethylpyridinium
tetrafluoroborate, N-butylpyridinium tetrafluoroborate, and
N-(2-hydroxypropyl)-pyridinium tetrafluoroborate] were
explored; the results are summarized in Table 1. It can
be seen from Table 1 that the reaction performed in
PEG-400, THF, and three ionic liquids afforded compara-
tively low yields at long reaction time. Whereas when
water was chosen as the reaction medium, the desired
product is not observed. Under the same conditions,
however, the best result (yield 99%, reaction time 3 min;
Table 1, entry 6) was obtained in dipolar aprotic solvent
DMSO. For the same reaction, if no ultrasonic irradiation,
only 81% of yield was obtained after 3 h (Table 1, entry 14).
The aforementioned results clearly demonstrate that the
N-alkylation of carbazole with bromoethane in DMF or
DMSO can be greatly accelerated by ultrasonic irradiation.
Main explanations for the acceleration under the ultrasonic
irradiation may be based on two effects: (i) vigorous agitation
makes the molecular reaction interact very well; and
(ii) momentary high temperature and great pressure generated
by the bubble collapse prompt the reaction greatly.
To test the generality of this approach, various alkyl
halides were allowed to react with carbazole in DMF or
DMSO. As is evident from Table 2, the ultrasound-assisted
N-alkylation reactions preceded smoothly; most of the alkyl
halides can be substituted with moderate to high yield. When
using 0.5 equiv of 1,4-dibromobutane or 1,3-dibromobutane
as alkylation agent, disubstituted products 1,4-di(carbazol-9-yl)
butane and 1,3-di(carbazol-9-yl)propane were obtained with
yield 90 and 89%, respectively (Table 2, entries 8 and 9).
However, when using 2 equiv of 1,4-dibromobutane in
the SN2 reaction of carbazole with 1,4-dibromobutane, the
reaction stopped at the monosubstituted stage, and only
monosubstituted compound N-(4-bromobutyl) carbazole
was obtained with the yield of 92% in DMSO after 80min
(Table 2, entry 7). The reasons for this may be attributed
to two factors: one is the steric effect on the substrate
alkyl halide, N-(4-bromobutyl) carbazole, is more hindered,
and then, 1,4-dibromobutane, the nucleophile, can easily
approach an electrophilic carbon atom of 1,4-dibromobutane
and produce the product N-(4-bromobutyl) carbazole. For
the N-(4-bromobutyl) carbazole, the further approach is
Table 1
Effect of solvent and the ultrasonic power on the N-alkylation reaction of
carbazole with bromoethane.
Entry Power (W)
Solvent
DMF
DMF
DMF
DMF
DMF
DMSO
PEG-400
H2O
Irradiation time Yield (%)a
1
2
3
4
5
6
7
8
9
10
40
60
80
90
100
90
90
90
90
90
30 min
30 min
30 min
6 min
6 min
3 min
3 h
57
64
82
98
89
99
67
ND
59
75
3 h
3 h
3 h
THF
11
12
90
90
3 h
3 h
70
56
13
80
0
DMSO
DMSO
3 min
3 h
86
81
14b
Conditions: The reactions were run with carbazole (5 mmol), KOH (10 mmol),
bromoethane (10 mmol), solvent (10 mL), and the reaction temperature 35ꢀC;
the reaction progress was monitored by TLC.
aRefers to work-up yield.
bConventional method with magnetic stirring.
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An Efficient Ultrasound-Assisted Synthesis of N-Alkyl Derivatives of Carbazole, Indole,
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Table 2
Alkylation of carbazole with different alkyl halides in DMSO and DMF.
Entry
1
Alkyl halide
Product
Irradiation time (min)
Solvent
Yield (%)a
6
3
DMF
DMSO
98
99
2
3
10
6
DMF
DMSO
97
98
150
110
DMF
DMSO
90
95
4
50
30
DMF
DMSO
96
98
5
6
240
180
DMF
DMSO
76
87
60
35
DMF
DMSO
94
97
7
125
80
DMF
DMSO
88
92
8b
90
75
DMF
DMSO
87
90
9b
130
100
DMF
DMSO
87
89
10b
240
240
DMF
DMSO
Trace
Trace
Conditions: All reactions except entries 8–10 were run with carbazole (5 mmol), KOH (10 mmol), and alkyl halide (10 mmol) in DMSO (10 mL) or DMF
(10 mL) with the reaction temperature 35ꢀC and the ultrasonic power 90 W;
aRefers to work-up yield;
bFor entries 8–10, the amount of alkyl halide is 0.25 mmol.
Journal of Heterocyclic Chemistry
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S. Zhao, J. Kang, Y. Du, J. Kang, X. Zhao, Y. Xu, R. Chen, Q. Wang, and X. Shi
Vol 51
hindered. Another factor is the concentration of alkyl halide;
when 2 equiv of 1,4-dibromobutane was used, the concentra-
tion of 1,4-dibromobutane is far higher than the concentra-
tion of the monosubstituted product N-(4-bromobutyl)
carbazole; thus, the reaction of carbazole with 1,4-dibromo-
butane is preferred, and the monosubstituted compound
is the main product. With the less reactive alkylation agent 2-
chloroethanol, longer reaction times are required (Table 2,
entry 5), and for the alkylation agent 1,2-dibromoethane,
1,2-dichloroethane, and 1,3-dichloro-2,2-bis(chloromethyl)
propane, trace or no product was detected.
Aiming to increase the scope of our methodology, we
next exploited our method to other heterocycles possessing
acidic hydrogen such as indole and phenothiazine. The
results presented in Tables 3 and 4 suggest that N-alkylation
of indole and phenothiazine with a variety of alkylation
agents proceeds smoothly with yields ranging from good
to excellent. In early reports [18], some C-alkylation is
observed when allylic or benzylic halides were used as
alkylation agents for the N-alkylation of indole. To further
confirm the advantages of our methodology, the allyl and
benzyl bromides were used as alkylation agents (Table 3,
entries 4 and 5); according to TLC, NMR, and GC analyses,
exclusive N-alkylation of indole can be produced with
high yield. It is noteworthy that the reactions of
0.5 equiv of 1,4-dibromobutane with indole (Table 3, entry
6) and phenothiazine (Table 4, entry 6) gave disubstituted
products 1,4-di(indol-1-yl)butane and 1,4-di(phenothiazin-
10-yl)butane with yield 84and 81%, respectively. Finally,
as we expected, when tert-butyl chloride was selected as
alkylating agent, no product was detected, and many bub-
bles were produced in the process of ultrasonic irradiation.
It may be caused by the elimination reaction of tert-butyl
chloride in the presence of KOH.
CONCLUSIONS
In summary, we have succeeded in developing the N-
alkylation of carbazole, indole, and phenothiazine with a
variety of alkylation agents under ultrasonic conditions.
Under the optimized conditions of ultrasonic irradiation,
a series of N-substituted derivatives of carbazole, indole,
Table 3
Alkylation of indole with different alkyl halides in DMSO.
Entry
1
Alkyl halide
Product
Irradiation time (min)
Yield (%)a
96
20
2
3
50
94
56
160
4
5
100
90
87
92
6 c
120
84
Conditions: All reactions except entry 6 were run with indole (5 mmol), KOH (10 mmol), alkyl halide (10 mmol) in DMSO (10 mL) with the reaction
temperature 35ꢀC and the ultrasonic power 90 W;
aRefers to work-up yield;
bFor entry 6, the amount of alkyl halide is 0.25 mmol.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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An Efficient Ultrasound-Assisted Synthesis of N-Alkyl Derivatives of Carbazole, Indole,
687
And Phenothiazine
Table 4
Alkylation of phenothiazine with different alkyl halides in DMSO.
Entry
1
Alkyl halide
Product
Irradiation time (min)
25
Yield (%)a
96
2
40
94
3
4
100
120
83
86
5
180
90
78
81
6 c
Conditions: All reactions except entry 6 were run with phenothiazine (5 mmol), KOH (10 mmol), and alkyl halide (10 mmol) in DMSO (10 mL) with the
reaction temperature 35ꢀC and the ultrasonic power 90 W;
aRefers to work-up yield;
bFor entry 6, the amount of alkyl halide is 0.25 mmol.
Ultrasonic Instrument Corporation, Suzhou, China), the reaction
flasks were located in the maximum energy area in the water bath,
where the surface of reactants is slightly lower than the level of the
water, and the reaction temperature was controlled by exchange of
the water in ultrasonic cleaning bath. Analytical TLC was carried
out using MN Kieselgel G/UV254 (Art.816320) glass-backed plates
(Qingdao Marine, Qingdao, China). All chemical reagents were
obtained from commercial suppliers and used without further
purification. Ionic liquids N-ethylpyridinium tetrafluoroborate, N-
butylpyridinium tetrafluoroborate, and N-(2-hydroxypropyl)-pyridi-
nium tetrafluoroborate were prepared according to the literature [19].
General procedure for the synthesis of N-substituted
carbazole, indole, and phenothiazine. To a solution containing
N-heterocyclic (5 mmol) in DMSO (10 mL) was added KOH
(10 mmol); the mixture was stirred at RT for 20 min. Then, the
appropriate alkyl chloride or alkyl bromide (10 mmol) was
added, and the reaction mixture was irradiated by 40 kHz
ultrasound at 35ꢀC. The reaction progress was monitored by
and phenothiazine were prepared and characterized by
1H and 13C NMR spectral, and elemental analyses. This
method displays dramatically reduced reaction time com-
pared with conventional methods and also affords the
desired products in moderate to high yields and purity.
EXPERIMENTAL
Melting points were measured on WRS-1B digital melting
point meter (Shanghai Jingke, Shanghai, China) and are uncor-
rected. 1H NMR and 13C NMR spectra were measured on a Bruker
Avance 500 MHz spectrometer (Bruker Corporation, Switzerland)
using TMS as an internal standard in CDCl3 (Supporting Informa-
tion). The elemental analyses were performed in the EuroEA3000
element analyzer (Erba Corporation, Italy). Sonication was per-
formed in Kunshan KQ-400KDE ultrasonic cleaner (with
frequency 40 KHz and maximum output power 400 W; Kunshan
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S. Zhao, J. Kang, Y. Du, J. Kang, X. Zhao, Y. Xu, R. Chen, Q. Wang, and X. Shi
Vol 51
TLC. Upon completion, the reaction mixture was partitioned
with Et2O (40 mL) and water (30 mL), the organic phase was
washed with brine (2 Â 30 mL) and dried over anhydrous
Na2SO4, and removal of solvent on a rotary vacuum evaporator
to yield the almost pure object product was carried out. Further
purification can be achieved by recrystallization from ethanol
or by column chromatography using petroleum ether–ethyl
acetate (5:1) as eluent.
N-Ethylindole (Table 3, entry 1) [21].
Oil; 1H NMR
(500 MHz, CDCl3): d = 8.17–8.15 (m, 1H), 7.73–7.70 (m, 3H),
7.43–7.42 (m, 1H), 6.98–6.97 (m, 1H), 4.40 (q, J = 7.5 Hz, 2H),
1.75 (J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): d = 135.5,
128.5, 126.7, 121.0, 120.7, 118.9, 109.0, 100.7, 40.4, 15.0.
N-Butylindole (Table 3, entry 2) [21].
Oil; 1H NMR
(500 MHz, CDCl3): d = 8.22 (d, J = 2.5 Hz, 1H), 7.85–7.67 (m,
3H), 7.47 (d, J = 3 Hz, 1H), 7.04 (d, J = 2 Hz, 1H), 4.41
(t, J = 7.1 Hz, 2H), 2.23–2.09 (m, 2H), 1.80–1.65 (m, 2H), 1.42
(t, J= 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3): d = 135.7, 128.4,
127.4, 121.0, 120.6, 118.9, 109.1, 100.5, 45.5, 31.9, 19.8, 13.4.
N-Decylindole (Table 3, entry 3). Oil; 1H NMR (500 MHz,
CDCl3): d = 7.98–7.97 (q, 1H), 7.62 (d, J = 8 Hz, 1H), 7.53
(t, J = 7 Hz, 1H), 7.46–7.44 (m, 1H), 7.33–7.32 (q, 1H),
6.82–6.81 (q, 1H), 4.32–4.28 (m, 2H), 2.08 (d, J = 6 Hz,
2H),1.6 (d, J = 5.5 Hz, 14H), 1.28–1.24 (m, 3H). 13C NMR
(125 MHz, CDCl3): d = 135.8, 128.2, 127.5, 121.1, 120.8,
119.0, 109.2, 100.7, 46.1, 34.2, 32.2, 30.1, 29.4, 29.2,
29.1, 26.9, 23.0, 14.0; Anal. Calcd for C18H27N: C, 83.99;
H, 10.57; N, 5.44. Found: C, 83.71; H, 10.60; N, 5.31.
N-Benzylindole (Table 3, entry 4) [21]. Colorless solid, mp
N-Ethylcarbazole (Table 2, entry 1) [3].
White solid, mp
68–69ꢀC (Lit. mp 67–68ꢀC); 1H NMR (500 MHz, CDCl3):
d = 8.06 (d, J = 5.0 Hz, 2H), 7.42 (d, J = 5.0 Hz, 2H), 7.33
(d, J= 10.0 Hz, 2H), 7.20–7.18 (t, J=5.0Hz, 2H), 4.27–4.22
(q, J= 7.0 Hz, 2H), 1.33(t, J=7.0Hz, 3H); 13C NMR (125 MHz,
CDCl3): d = 139.8, 125.5, 122.89, 120.3, 118.7, 108.3, 37.3, 13.7.
N-Butylcarbazole (Table 2, entry 2) [3]. White solid; mp
59–60ꢀC (Lit. mp 58–59ꢀC); 1H NMR (500 MHz, CDCl3):
d = 8.09 (d, J = 12.5 Hz, 2H), 7.47–7.43 (q, J = 12 Hz, 4H),
7.40–7. 19(m, 2H), 4.29 (t, J = 12.0 Hz, 2H), 1.89–1.79 (m, 2H),
1.43–1.35 (m, 2H), 0.93 (t, J = 12 Hz, 3H); 13C NMR
(125 MHz, CDCl3): d = 140.4, 125.5, 122.8, 120.3, 118.6,
108.6, 42.8, 31.1, 20.5, 13.8.
1
N-Decylcarbazole (Table 2, entry 3) [3].
Oil; 1H NMR
42ꢀC (Lit. mp 41–42ꢀC); H NMR (500 MHz, CDCl3): d = 7.64
(500 MHz, CDCl3): d = 8.14 (d, J = 10 Hz, 2H), 7.50–7.42
(q, J= 15 Hz, 4H), 7.26 (t, J= 15 Hz, 2H), 4.31 (t, J= 10.0 Hz, 2H),
1.89 (t, J= 10.0 Hz, 2H), 1.28 (s, 14H), 0.93 (t, J=5Hz, 3H); 13C
NMR (125 MHz, CDCl3): d = 140.3, 125.4, 122.7, 120.2, 118.6,
108.5, 42.9, 29.4, 29.4, 29.3, 29.2, 28.8, 27.2, 22.5, 14.0.
(d, J = 7.8 Hz, 1H), 7.37–7.21 (m, 4H), 7.12–6.80 (m, 5H), 6.53
(d, J = 2.8 Hz, 1H), 5.24 (s, 2H); 13C NMR (125 MHz, CDCl3):
d = 137.4, 136.2, 128.6, 128.1, 127.5, 126.7, 121.6, 120.9,
119.4, 109.6, 101.6, 49.9.
N-Allylindole (Table 3, entry 5) [10].
Oil; 1H NMR
N-Allylcarbazole (Table 2, entry 4) [20a]. White solid, mp
(500 MHz, CDCl3): d = 8.15 (d, J = 7.5 Hz, 1H), 7.73–7.69 (m,
3H), 7.44 (t, J = 1.5 Hz,1H), 7.00 (s, 1H), 6.32 (t, J = 6.5 Hz,
1H), 5.57 (d, J = 10.5 Hz, 1H), 5.47 (s, 1H), 4.97–4.93 (m, 2H);
13C NMR (125 MHz, CDCl3): d = 135.9, 133.3, 128.5, 127.6,
121.3, 120.7, 119.2, 116.7, 109.4, 101.1, 48.3.
1
55ꢀC (Lit. mp 55–56ꢀC); H NMR (500 MHz, CDCl3) : d = 8.07
(d, J=8.0Hz, 2H), 7.40 (t, J=7.0Hz, 2H), 7.31 (d, J=8.5Hz, 2H),
7.20 (s, 2H), 5.94–5.89 (m, 1H), 5.11–5.09 (m, 1H), 4.99–4.96
(m, 1H), 4.81–4.80 (m, 2H); 13C NMR (125 MHz, CDCl3)
d = 140.3, 132.2, 125.6, 122.9, 120.3, 119.0, 116.7, 108.7, 45.1.
1,4-Di(indol-1-yl)butane (Table 3, entry 6).
White solid;
2-(Carbazol-9-yl)ethanol (Table 2, entry 5) [20b].
White
mp 91–92ꢀC; 1H NMR (500 MHz, CDCl3): d = 7.62 (d,
J = 10 Hz, 2H), 7.24 (d, J = 10 Hz, 2H), 7.18 (t, J = 5 Hz, 2H),
7.09 (d, J = 5 Hz, 2H), 6.46 (s, 1H), 4.00 (t, J = 5 Hz, 4H), 1.77
(t, J = 5 Hz, 4H); 13C NMR (125 MHz, CDCl3): d = 135.8,
128.5, 127.5, 121.4, 121.0, 119.3, 109.2, 101.2, 45.8, 27.6;
Anal. Calcd for C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found:
C, 83.41; H, 7.14; N, 9.59.
solid, mp 78ꢀC; 1H NMR (300 MHz, CDCl3): d = 8.10 (d,
J = 15.0 Hz, 2H), 7.47 (t, J = 5.0 Hz, 4H), 7.26–7.23 (q,
J = 5.0 Hz, 2H), 4.46 (t, J = 7.5 Hz, 2H), 4.03 (t, J = 10.0 Hz,
3H); 13C NMR (CDCl3, 125 MHz): d = 140.6, 125.8, 122.9,
120.3, 119.1, 108.7, 61.4, 45.4.
N-Benzylcarbazole (Table 2, entry 6) [3]. White solid, mp
1
117–118ꢀC (Lit. mp 118-119ꢀC); H NMR (500 MHz, CDCl3) :
N-Ethylphenothiazine (Table 4, entry 1) [20a]. Light green
crystal, mp 100–101ꢀC (Lit. mp 102.5–103ꢀC); 1H NMR
(500 MHz, CDCl3): d = 7.15–7.10(m, 4H), 6.91–6.83 (m, 4H),
3.93–3.86 (q, J = 10 Hz, 2H), 1.39 (t, J = 10 Hz, 3H); 13C NMR
(125 MHz, CDCl3): d = 144.9, 127.3, 127.1, 124.4, 122.2,
115.0, 41.6, 12.9.
d = 8.11 (d, J = 8.0 Hz, 2H), 7.39 (s, 2H), 7.32 (d, J = 8.0 Hz,
2H), 7.22–7.20 (m, 5H), 7.09 (d, J = 6.5 Hz, 2H), 5.45 (s, 2H);
13C NMR (125 MHz, CDCl3) d = 140.6, 137.1, 128.7, 127.4,
126.3, 125.8, 122.5, 120.3, 119.1, 108.8, 46.5.
N-(4-Bromobutyl) carbazole (Table 2, entry 7) [20c]. White
solid, mp 198–199ꢀC; 1H NMR (500 MHz, CDCl3): d = 8.07–8.05
(m, 2H), 7.43–7.33 (m, 2H), 7.22–7.18 (m, 4H), 4.25 (t,
J = 7.0 Hz, 2H), 3.29 (t, J = 6.5 Hz, 2H), 2.00–1.96 (m, 2H),
1.87–1.82 (m, 2H); 13C NMR (125 MHz, CDCl3): d = 140.2,
125.6, 122.8, 120.3, 118.9, 108.5, 42.6, 33.0, 30.1, 27.5.
1,4-Di(carbazol-9-yl)butane (Table 2, entry 8) [20d]. White
solid, mp 189ꢀC; 1H NMR (400 MHz, CDCl3): d = 8.07 (d,
J = 7.00 Hz, 4H), 7.41 (t, J = 7.5 Hz, 4H), 7.24–7.19 (m, 8H),
4.14 (s, 4H), 1.90 (s, 4H); 13C NMR (CDCl3, 125 MHz):
d = 140.2, 125.6, 122.8, 120.3, 118.8, 108.5, 42.6, 26.7.
1,3-Di(carbazol-9-yl)propane (Table 2, entry 9) [20d]. White
solid, mp 181ꢀC; 1H NMR (300 MHz, CDCl3): d = 8.07
(d, J = 13 Hz, 4H), 7.38–7.33 (m, 4H), 7.22–7.12 (s, 8H),
4.29–4.24(t, J = 12 Hz, 4H), 2.37–2.27(t, J = 12 Hz, 4H); 13C
NMR (CDCl3, 125 MHz): d = 140.0, 125.7, 122.9, 120.4, 119.0,
108.3, 40.4, 27.7.
N-Butylphenothiazine(Table 4, entry 2) [22b]. Oil; 1H NMR
(500MHz, CDCl3): d =7.22–7.17(m, 4H), 6.92 (t, J = 15Hz, 4H),
3.88 (t, J = 10 Hz, 2H), 1.83 (t, J = 10 Hz, 2H), 1.54–1.46 (m, 2H),
0.99 (t, J = 10 Hz, 3H); 13C NMR (125MHz, CDCl3):
d = 145.2,127.2, 127.0, 124.8, 122.1, 115.3, 46.9, 28.9, 20.0, 13.7.
N-Decylphenothiazine(Table 4, entry 3) [22c].
Oil; 1H
NMR (500 MHz, CDCl3): d = 7.13(d, J = 15 Hz, 4H), 6.88 (t,
J = 15 Hz, 4H), 3.84 (t, J = 10 Hz, 2H), 1.89–1.79 (m, 2H),
1.44–1.29 (m, 14H), 0.90 (t, J = 10 Hz, 3H); 13C NMR
(125 MHz, CDCl3): d = 145.2, 127.3, 127.0, 124.8, 122.2,
115.3, 47.3, 31.8, 29.4, 29.4, 29.4, 29.2, 28.7, 28.1, 22.6, 14.0.
N-Benzylphenothiazine (Table 4, entry 4) [22a].
White
1
solid, mp 90–91ꢀC (Lit. mp 90.0–90.5ꢀC); H NMR (500 MHz,
CDCl3): d = 7.40–7.30(m, 9H), 7.12–6.85 (t, 4H), 5.10 (s, 2H);
13C NMR (125 MHz, CDCl3): d = 144.3, 141.5, 128.9, 128.3,
127.7, 127.1, 126.8, 126.4, 122.4, 115.3, 65.1.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
An Efficient Ultrasound-Assisted Synthesis of N-Alkyl Derivatives of Carbazole, Indole,
689
And Phenothiazine
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N-Isobutylphenothiazine (Table 4, entry 5). White solid, mp
1
123–125ꢀC; H NMR (500 MHz, CDCl3): d = 7.26–7.13(m, 4H),
6.93–6.86 (m, 4H), 3.73–3.64 (m, 2H), 2.23–2.18 (m, 1H), 1.00
(d, J = 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): d = 145.8,
127.5, 127.1, 125.8, 122.3, 115.9, 55.1, 25.4, 20.1; Anal. Calcd
for C16H17NS: C, 75.25; H, 6.71; N, 5.48. Found: C, 75.31; H,
6.64; N, 5.71.
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Acknowledgments. We gratefully acknowledge financial support
from the Higher School Science & Technology Development
Project of Shanxi Province Education Department (No. 2010124),
the Higher School Students Creation and Innovation Training
Project of Shanxi Province ([2011]11, No. 2011332), and Project
of Xinzhou Teachers University ([2011] 52).
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Chem 2006, 258, 251; (b) Holbrey, J. D.; Turner, M. B.; Reichert, W.
M.; Rogers, R. D. Green Chem 2003, 5, 731.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet