Synthesis of 2-(9H-carbazol-1-yl)anilines from 2,3′-biindolyl and ketones

Article abstract of DOI:10.1016/j.tet.2018.03.066

Twenty-nine examples of 2-(9H-carbazol-1-yl)anilines were obtained in yields from 27 to 95% by refluxing 2,3′-biindolyl (1 equiv.) and ketones (1 equiv.) in ethanolic HCl. Alkyl, cyclic, and aryl ketones were found to be compatible with this method, however, aldehydes are not. Because the reaction proceeds by addition of the carbonyl C atom to the biindolyl 3-position, this method has high regioselectivity. One example is presented of bridging the two N atoms in the carbazolylaniline product with an acetaldehyde synthon to give a benzodiazepino[lm]carbazole. Also, one example is given of installing a dimethylamino group at the α-position of the starting ketone to give an indolo[3,2-c]carbazole.

Full text of DOI:10.1016/j.tet.2018.03.066

Accepted Manuscript
Synthesis of 2-(9H-carbazol-1-yl)anilines from 2,3′-biindolyl and ketones
Wayland E. Noland, Christopher D. Brown, Abigail E. Zabronsky, Kenneth J. Tritch
PII:
S0040-4020(18)30339-9
10.1016/j.tet.2018.03.066
TET 29406
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 February 2018
Revised Date: 26 March 2018
Accepted Date: 28 March 2018
Please cite this article as: Noland WE, Brown CD, Zabronsky AE, Tritch KJ, Synthesis of 2-
(9H-carbazol-1-yl)anilines from 2,3′-biindolyl and ketones, Tetrahedron (2018), doi: 10.1016/
j.tet.2018.03.066.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Synthesis of 2-(9H-carbazol-1-yl)anilines from 2,3'-biindolyl
and ketones
Wayland E. Noland; Christopher D. Brown; Abigail E. Zabronsky; Kenneth J. Tritch
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, United States
TOC Graphic:
O
R2
R1
1) HCl, EtOH, reflux
R2
R1
2) Na2CO3 (aq. sat.)/ EtOAc
(1:1 v/v)
Metal-free
Oxidant-free
High Regioselectivity
Gram-scale
NH
NH2
N
N
H
H
27-95%
29 examples
Keywords: 2,3'-biindolyl, ketones, substituted carbazoles, cyclizative condensation, metal-free
Abstract: Twenty-nine examples of 2-(9H-carbazol-1-yl)anilines were obtained in yields from
27-95% by refluxing 2,3’-biindolyl (1 equiv.) and ketones (1 equiv.) in ethanolic HCl. Alkyl,
cyclic, and aryl ketones were found to be compatible with this method, however, aldehydes are
not. Because the reaction proceeds by addition of the carbonyl C atom to the biindolyl 3-
position, this method has high regioselectivity. One example is presented of bridging the two N
atoms in the carbazolylaniline product with an acetaldehyde synthon to give a
benzodiazepino[lm]carbazole. Also, one example is given of installing a dimethylamino group at
the α-position of the starting ketone to give an indolo[3,2-c]carbazole.
1. Introduction
Carbazoles are heterocyclic compounds that are commonly observed in naturally
occurring alkaloids [1] and synthetic derivatives, many of which show a wide range of biological
activities including anticancer and antitumor [2], anti-inflammatory [3], antibacterial [4], anti-
oxidative [5], and neuroprotective properties [6], among others [7]. Carbazoles also have
1

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
potential applications in optoelectronic materials [8], polymers [9], and synthetic dyes [10].
Hence, carbazoles have maintained the interest of the chemistry community, and synthetic
strategies continue to be developed for accessing new carbazole derivatives with good
regioselective control. Transition-metal-catalyzed syntheses of carbazoles have been extensively
explored to accomplish such objectives [11].
Several examples of transition-metal-free carbazole syntheses have also been reported.
These include a modified Fischer-Borsche carbazole synthesis (Scheme 1a) [12], an
intramolecular electrophilic amination of arene C–H bonds (Scheme 1b) [13], an intramolecular
dehydrogenative annulation using iodine (III) reagents (Scheme 1c) [14], and a Diels-Alder-
oxidation cascade (Scheme 1d) [15]. Collectively, these four examples cover a wide range of
carbazoles. However, the first three examples have limited control over regioselection due to
multiple annulation possibilities, the second example is limited to functional groups that don’t
interfere with magnesium transmetallation, and the last two examples require substitution at the
carbazole N atom.
2

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
a.
NH2•HCl
HN
O
R1 = alkyl, aryl, OCH3, SCH3,
O2
R1
R1
+
CO2R, halo, CN
R2 = H, alkyl, halo, OCH3, ring-fused
R3 = acyl, sulfonyl
NMP, 120oC
N
H
b.
c.
d.
R2
R2
PhMgBr (3 equiv)
THF, 0 oC, 15 min
R4 = alkyl, halo
R5 = alkyl
NH
NO2
R1
R1
R6, R7: alkyl, aryl, or cyclic ketones
EWG = CO2R, CN
R2
iodine (III)
R1
R2
R1
+
N
R3
NH
R3
solvents, 1 h
R7
R7
R6
R6
N
O2
O
EWG
+
R4
R7
R4
R4
+
R6
N
R5
EWG
EWG
N
R5
R5
Scheme 1. Selected transition-metal-free syntheses of substituted carbazoles
Past reports have shown that 2,3'-biindolyl 3 is a versatile building block for synthesis of
cycloheptadiindoles, indolocarbazoles, and related aza analogues [16,17]. Here, we disclose
access to 2-(9H-carbazol-1-yl)anilines via cyclizative condensation of 3 with alkyl, cyclic, and
aryl ketones under metal- and oxidant-free conditions.
2. Results and Discussion
Compound 3 was prepared according to the literature [16a] by the dimerization of indole
1 in anhydrous hydrochloric ether, followed by palladium-catalyzed dehydrogenation of dimer 2
in refluxing toluene in 65% overall yield (Scheme 2a). Compound 3 has also been prepared in
metal-free conditions, by the addition bromine to a solution of 1 in acetonitrile in 80% yield
(Scheme 2b) [18].
3

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Scheme 2. The preparation of 3 from 1 via (a) acid-catalyzed dimerization and then
dehydrogenation; (b) bromine-promoted oxidative dimerization of 1.
Based on previous work in our laboratories [19], refluxing ethanolic hydrochloric acid
was a reasonable starting point for the optimization of reaction conditions (Table 1, entry 1).
Cyclohexanone 4e was chosen as the test substrate, because of its low cost and good behavior in
preliminary trials. Among the different acid and solvent mixtures attempted, hydrochloric acid in
refluxing ethanol or acetonitrile (Table 1, entries 1-2) gave the highest yields of 5e, 88 and 91%
respectively, and the lowest yields of side products. p-TsOH and TFA gave mixtures of 5e with
6e and 7e (Table 1, entries 3-11), while dilute AcOH was too mild (Table 1, entries 12-15). The
original condition (Table 1, entry 1) was chosen as the optimized condition because of much
faster conversion of 3 into 5e versus use of acetonitrile, with a minimal loss of yield.
O
acid
NH
NH
NH
NH2
+
+
+
N
N
N
N
solvent
H
H
H
H
3
4e
5e
6e
7e
4

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Temp (oC)
Time
Yield (%)a
Yield (%)a
Yield (%)a
Conversion (%)h
Entry
Acid
Solvent
5e
88
91
69
17
78
1.4
6e
0
7e
1
2
HClb
EtOH
MeCN
EtOH
reflux
reflux
reflux
reflux
reflux
reflux
6 h
2 d
2 d
2 d
2 d
2 d
0
91
92
78
22
83
7
HClb
0
0g
0
3
p -TsOHc
p -TsOHc
p -TsOHc
p -TsOHc
TFAd
TFAd
TFAd
TFAd
5
4
MeCN
toluene
CHCl3
EtOH
4.4
0
0g
0g
0
5
6
1.6
7
70
70
70
70
2 d
2 d
2 d
2 d
47
76
4.6
0g
14
0
0g
0g
5
4.6
0
68
82
5
8
MeCN
toluene
CHCl3
TFAf
9
10
11
12
13
14
15
16
0
0g
<1
19
30
12
32
31
>99
---
70
2 d
2 d
2 d
2 d
2 d
0g
7.3
20
1.8
28
10
0
AcOHe
AcOHe
AcOHe
AcOHe
EtOH
reflux
reflux
reflux
reflux
0
0
MeCN
toluene
CHCl3
AcOHf
0
0g
0
2.5
0
0
reflux
1 d
---
78
16
Table 1. Optimization of the synthesis of 5e. aCalculated by 1H NMR analysis.
Compounds 3 (4.305 mmol, 1 equiv) and 4e (4.305 mmol, 1 equiv) were dissolved in 40 mL of
b
c
either ethanol, acetonitrile, toluene, or chloroform. Acid: conc. HCl (5 mL); p-TsOH (10
d
e
f
mol%); TFA (5 equiv.); AcOH (5 equiv.); either TFA or AcOH (5 mL) were used as the
g
1
h
solvent. Trace amounts were observed in H NMR spectra. Conversion of 3 calculated by 1H
NMR analysis.
A selection of 30 alkyl, cyclic, aryl, and heterocyclic ketones were exposed to the
optimized conditions on a gram scale or larger (Scheme 3). Alkyl ketones 4a-c required
relatively long reaction times compared to the other types of ketone. For cyclic ketones, ring
sizes 5-8 4d-g performed better than alkyl ketones. The larger ring sizes 4h-k reacted more
slowly. Cyclobutanone 8 gave an inseparable, tarry mixture.
5

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
1) HCl, EtOH, reflux
2) sat. Na2CO3/ EtOAc
(1:1 v/v)
R2
R1
O
NH
NH2
R2
+
R1
N
H
N
H
3
4a-z
5a-z
R
H3C
n
CH3
CH3
H3C
H3C
NH2
NH2
NH2
NH2
N
NH2
N
H
N
N
N
H
H
H
H
5a, 37%, 9d
5b, 52%, 11d
5c, 55%, 12d
5d, n=1, 95%, 24h
5e, n=2, 84%, 3h
5f, n=3, 55%, 6d
5g, n=4, 43%, 10d
5h, n=5, 44%, 14d
5i, n=6, 45%, 13d
5j, n=7, 27%, 14d
5k, n=8, 48%,14d
5l, R=H, 87%, 3d
5m, R=CH3,42%, 6d
5n, R=NH2, 92%, 5d
5o, R=OH, 76%, 5d
5p, R=OCH3, 53%, 5d
5q, R=Cl, 86%, 4d
5r, R=Br, 82%, 3d
Cl
Cl
Cl
OCH3
H3CO
NH2
CH3
NH2
NH2
N
H
N
H
N
H
5s, 65%, 3d
5t, 93%, 3d
5u, 81%, 3d
O
S
N
NH2
NH2
NH2
NH2
NH2
N
H
N
H
N
H
N
H
N
H
5y, 72%, 6d
5v, 72%, 2d
5w, 36%, 2d
5x, 69%, 3d
5z, 74%, 3d
Incompatible Ketones
O
CH3
O
O
O
(H3C)3 CH3
N
H3C
CH3
N
H
8
9
10
11
Scheme 3. Synthesis of 2-(9H-carbazol-1-yl)anilines from various ketones.
Monosubstituted acetophenones with electron-donating substituents (i.e., 4m and 4p)
gave lower yields than those with electron-withdrawing substituents (i.e., 4q and 4r), or 4n,
which probably is protonated in solution. The use of propiophenone 4s gave slightly lower yield
than that of acetophenone 4l, but interestingly outperformed 4-methylacetophenone 4m.
6

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Multisubstituted acetophenones 4t and 4u both gave comparatively high yields. The yields from
heteroaryl ketones 4v and 4x-z were near the middle of the aryl ketone range. In spite of being
electron-deficient, 2-acetylpyridine 4w gave a low yield. Neither aryl ketones 2-acetyl-N-
methylpyrrole 9 and 3-acetylindole 10, nor hindered 3,3-dimethyl-2-butanone 11 gave any
identifiable products. Several alkyl aldehydes were also tried, giving complex, tarry mixtures
that were not explored further.
The easiest method of isolating products 5a-z from the reaction mixtures was to first
obtain the corresponding hydrochloride salts by removing the ethanol at reduced pressure.
Trituration of the resulting residue with ether removed most of the leftover ketone, except for 4n,
which was highly persistent, before and after neutralization or chromatography. The resulting
residues were neutralized with a biphasic mixture of ethyl acetate and aqueous sodium carbonate,
followed by separation by column chromatography. For many of the methyl aryl ketone-derived
products 5l-w, residual solvents could not be removed completely.
The preceding ketones are either symmetrical (Scheme 4a) or have one quaternized α-
position (Scheme 4b), allowing only one regioisomer of type 5 products to form. To test the
regioselectivity of this method, 2-pentanone 12 was allowed to condense with 3 (Scheme 4c).
Products 13 and 14 were obtained as a 15:1 mixture, which could not be resolved by flash
chromatography nor fractional crystallization. The major product is the more highly substituted
carbazole 13.
7

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
a.
O
H3C
CH3
NH2
H3C
3
CH3
N
H
4b
5b
b.
O
3
NH2
CH3
N
H
4l
5l
H3C
c.
CH3
NH2
H3C
O
3
NH2
+
H3C
CH3
N
N
H
H
12
13
14
15:1 mixture
Scheme 4. Regioisomerism in the condensation of 3 with ketones, with arrows denoting
corresponding C atoms before and after annulation. (a) Symmetrical or (b) α-quaternized ketones
give a single regioisomer; (c) Other unsymmetrical ketones can form two regioisomers.
In two examples, plain biindolyl 3 was replaced by substituted biindolyls, 16 and 19
(Scheme 5). Compound 16 was prepared from 5-methoxyindole 15 by the same sequence used to
prepare 3 [16a]. For compound 19, the dehydrogenation was replaced by oxidation by DDQ,
because complications were encountered that were probably derived from oxidative addition of
the aryl bromide to palladium. Although the yields of substituted biindolyls 16 and 19 were
substantially lower than the yield of 3, the cyclizative condensation portion of the synthesis gave
products 17e in 89% yield, higher than 4e condensing with 3 (84%). Product 20e was obtained in
8

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
somewhat lower yield (59%), indicating that this method could be most compatible with
electron-rich or electron-neutral biindolyls.
Scheme 5. Synthesis of substituted 2-(9H-carbazol-1-yl)anilines 17e and 20e. Conditions: (a)
o
Dimerization: 1) anhydrous HCl in ether, 0 C; 2) EA, Na2CO3, H2O; Oxidation: Pd/C, toluene,
o
reflux; (b) Dimerization: 1) anhydrous HCl in ether, 0 C; 2) EA, Na2CO3, H2O; Oxidation:
DDQ, 1,4-dioxane, reflux; (c) 1) 4e, HCl, EtOH, reflux; 2) EA, Na2CO3, H2O.
The aforementioned work was inspired by previous work in our laboratory, in which
condensation reactions of indole 1 with cyclic ketones in the presence of Brønsted acids were
explored [19]. The smaller cyclic ketones 8, 4d, and 4e gave 2:2 (-2 H2O) condensation products
21-23 [20a-c] (Scheme 6). These reactions proceeded quickly and showed no discernible
mixtures with biindolyl 3. Condensation between 1 and the larger cyclic ketones 4f-4k proceeded
slowly and gave mixtures of 3 and other products, suggesting that 1 can slowly convert to 3 in
the presence of acid, most notably TFA, and oxygen, by a pathway similar to Scheme 2a.
9

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
O
O
H
4e
4g
N
NH
+
a
d
N
N
H
N
N
N
H3C
H
H
H
3, 4.5%
24, 2.1%
O
23, 34%
1
O
c
b
4d
8
24, 53%
e
N
N
H
OEt
H3C OEt
H
5g
HN
22, 41%
+
HN
21, 35%
Scheme 6. Reactions of indole with cyclic ketones in the presence of a Brønsted acids.
o
o
Conditions: (a) HCl, CH3CN, 0 C, 24 h; (b) HCl, EtOH, rt, 5 d; (c) HCl, 75 C, 5 d; (d) TFA,
EtOH, air, 50 oC, 8 d; (e) Cs2CO3, EtOH, reflux, 3 d.
The most interesting cyclic ketone was cyclooctanone 4g, which gave
benzodiazepinocarbazole 24 from a one-pot reaction with 1 (Scheme 6d) [19] and no
corresponding products of type 7 were observed. It was postulated that the cascade leading to 24
included carbazole 5g, which was not observed in one-pot trials. A possible source of the
acetaldehyde unit in 24 is oxidation of ethanol by H2O2 that was generated in situ during the
formation of 3. In a separate experiment, 24 was prepared in 53% yield from 5g and 1,1-
diethoxyethane (Scheme 6e). The molecular structures of 5g and 24 were confirmed by X-ray
diffraction analysis (Fig. 1).
10

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Fig. 1. Views of crystalline (a) 5g and (b) 24, showing 50% thermal ellipsoids at 123 K, with C-
bound H atoms and C atom labels omitted for clarity. The N–H atoms are drawn as spheres of
arbitrary size.
During the same study of indole 1 with cyclic ketones [19], indolo[3,2-a]carbazoles 7f
and 7k were obtained from 4f and 4k, respectively (Scheme 7). Additionally, no products of
type 5 or annulations products similar to 24 were observed. It was these results, from 1 reacting
with 4f, 4g, and 4k, that initially sparked our interest to explore which types of ketones or
aldehydes could give products of type 5 or 7 from biindolyls of type 3.
O
O
4f
4k
a
b
NH
NH
N
H
N
N
H
H
1
7f, 4.4%
7k, 4.1%
Scheme 7. Ring-fused indolo[3,2-a]carbazoles isolated from the reaction of 1 with 4f and 4k in
the presence of trifluoroacetic acid. Conditions: (a) TFA, EtOH, 50 oC, 7d; (b) TFA, 50 oC, 7d.
11

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
A plausible reaction mechanism is presented, with 4e as the ketone example (Scheme 8).
Acid-promoted cyclizative condensation with 3 gives 25, a pathway supported by the presence of
6e in optimization mixtures (Table 1). Loss of a proton from 25 gives key intermediate 26. Acid-
catalyzed ring opening of 26 gives products of type 5, a pathway similar to the indoline ring-
opening during the trimerization of indole 1 [21a,b]. Alternatively, oxidation of 26 leads to
aromatized products of type 7. Thus, strong acids, including ethanolic HCl, favor the formation
of type 5 products. Type 7 products are hypothetically accessible by a combination of a weak
acid and an oxidant, such as hydrogen peroxide in acetic acid. However, as described in Table 1,
the condensation of 3 with ketones is impractically slow in weak acids. No conditions were
found by which products of type 7, aside from 7e, could be prepared directly from 3 and ketones
or aldehydes. This mechanism also explains the regioselectivity observed from 2-pentanone 12
(Scheme 4c), where among the intermediates to products 13 and 14, the corresponding analog of
6e favored by Zaitsev’s rule leads to product 13, the more highly substituted option.
12

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
H
H
H
H
NH
O
NH
H
[H+]
+H+
H
+
N
H
N
H
N
NH
H
H
-H2O
3
4e
6e
25
-H+
H
NH2
H
NH
+H+
N
N
H
H
NH2
N
H
H
H
H
26
O2
-H+
5e
28
OOH
NH
N
H
NH
N
H
H
-HOOH
7e
27
Scheme 8. A plausible mechanism for the formation 2-(9H-carbazol-1-yl)anilines (e.g., 5e) and
indolo[3,2-a]carbazoles (e.g., 7e) in the presence of acid and air.
Even though products of type 7 are not easily prepared directly from 3 condensing with
ketones, Janosik & Bergman gave one example, compound 30, that was prepared from
acetaldehyde synthon 29, which has a dimethylamino group at the α-position (Scheme 9a) [16b].
The dimethylamino group fulfills the role of the hydroperoxy group in intermediate 27 (Scheme
8), expediting the route to type 7 products both by serving as a superior leaving group and by
removing the kinetic bottleneck imposed by air oxidation of 26. In the present study, 2-
dimethylaminocyclohexanone 33 was prepared from cyclohexene oxide 31, and then exposed to
3 in refluxing acetic acid (Scheme 9b). Compared to plain cyclohexanone 4e (Table 1, entry 16),
the dimethylamino group in 33 slowed the overall rate of conversion, but shifted the product
selectivity such that carbazole 7e was obtained at 57% yield after 24 h, with no traces of type 5
13

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
1
products observed by H NMR analysis. Although no other examples were tested, it seems
reasonable that other analogs of 7e could be accessible via cyclizative condensation of 3 with the
corresponding α-dimethylamino ketones, especially those whose parent ketones condense with 3
in refluxing acetic acid at a practical rate. Attempts at synthesizing products of type 7 from
ketones and 3 in the presence acid and oxidants (i.e. H2O2 and MnO2) proved to be ineffective
and resulted in tarry, inseparable mixtures that were not explored further.
a.
NH
NH
c
OEt
+
N(CH3)2
N
N
H
EtO
H
29
3
30, 91%
b.
OH
O
O
N(CH3)2
N(CH3)2
d
e
33, 48%
31
32, 67%
NH
f
33 + 3
N
H
7e, 57%
Scheme 9. (a) Synthesis of indolo[3,2-a]carbazole from 3 and 29, as described by Janosik &
Bergman. (b) Synthesis of 33 and its use for the formation of ring-fused indolo[3,2-a]carbazole
7e. Conditions: (c) AcOH, reflux, 6h; (d) NH(CH3)2•HCl, K2CO3, Ethanol:THF:H2O (1:2:2 v/v),
reflux 6 h; RT 3 d; (e) Swern oxidation; (f) AcOH, reflux, 24 h.
3. Conclusion
Cyclizative condensation of 2,3'-biindoyl 3 with alkyl, cyclic, and aryl ketones in
ethanolic HCl is an effective means of preparing 2-(carbazol-1-yl)anilines. Aldehydes were
14

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
found to be incompatible with this preparation. This method has high regioselectivity among
annulation-based preparations of substituted carbazoles, and is compatible with substituted 2,3’-
biindolyls, as long as the 3- and 2’-positions are available for annulation. Due to the sluggish
nature of product formation and long reaction durations, further studies could be focused on
applying Lewis acid or combined acid activation of ketones for an one-pot synthesis of 2-
(carbazol-1-yl)anilines from 2,3'-biindolyls in a timely, selective manner. Additionally,
corresponding indolo[3,2-c]carbazoles might be accessible by adding a dimethylamino group at
the α-position of the ketone component, and there may be potential for further annulation by
constructing a bridge between the two N atoms of a given carbazolylaniline, or other
manipulations of the aniline system. However, the scope and efficiency of these synthetic
extensions remains to be studied.
4. Experimental
4.1. General information:
Melting points were measured with a Mel-Temp apparatus and were not calibrated or corrected.
Reaction progress was monitored by TLC (on SiO2 in 1:2 EA:hexane), with visualization by 254
or 365 nm light, and the use of iodine, ninhydrin, or vanillin stain as needed. All purifications by
column chromatography were performed on SiO2 using EA:hexane as the eluent. Infrared spectra
1
13
were collected on a Thermo Fisher Scientific Nicolet iS5 spectrophotometer. H NMR and C
NMR spectra were recorded on an AM-400 Bruker Avance III HD or AV-500 Bruker Avance III
HD spectrometer at ambient temperature and are referenced to the solvent. Mass spectra were
recorded on a Bruker BioTOF II ESI/TOF-MS instrument using poly(ethylene oxide) as an
internal calibrant, or on an Agilent 7890B gas chromatograph using an Agilent DB-5MS 250 μm
capillary column with an Agilent 7200 GC/QTOF-MS detector calibrated with external
15

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
perfluorotributylamine. Elemental analyses were performed by Atlantic Microlab, Norcross, GA,
USA; no elemental analyses were obtained for novel compounds 5v, 5w, 5z, 6e, or 19.
Cyclononanone was prepared via a modified procedure [22]. 2,3'-Biindolyl 3 was prepared
according to the literature [16a]. Other reagents and solvents were used as purchased.
4.2. General method for the syntheses of 2-(9H-carbazol-1-yl)anilines (5a-z, 13, 17e, 20e):
2,3'-Biindolyl 3 (3.00 g, 12.92 mmol, 1 eq) and respective ketone 4a-z (12.92 mmol, 1 eq) were
dissolved in EtOH (110 mL). HCl (12 M, 15 mL, 180 mmol) was added via syringe dropwise
over several minutes at RT. The resulting yellow-orange suspension was refluxed and the
duration of each reaction is listed below. The reaction mixture was then allowed to cool to RT
and the hydrochloric acid in EtOH was removed under reduced pressure to dryness. The isolated
solids were triturated either in hexane (when cyclic ketones were used) or Et2O (when other
ketones were used). The trituration solvent was decanted, giving the crude hydrochloride salts of
5a-z. The crude hydrochloride salts of 5a-z were stirred vigorously in a biphasic solution of EA
o
(50 mL) and Na2CO3 (aq. sat., 50 mL) in a 250 mL Erlenmeyer flask at 50 C for 2 h. The
biphasic solution was allowed to cool and separate, after which the organic layers were extracted
with EA (3 × 25 mL). The combined organic extracts were dried over anhydrous sodium sulfate,
filtered, and excess solvent was removed under reduced pressure. The products 5a-z were
purified by column chromatography, unless noted otherwise.
4.2.1. 2-(4-Methyl-9H-carbazol-1-yl)aniline (5a)
Was prepared according to the general method from 2,2-dimethoxypropane 4a (2.10 mL) as an
off-white crystalline powder (1.344 g, 37%, 9 d). mp 129.5-131˚C (from 2-propanol); Rf = 0.58;
16

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
IR (KBr, cm-1): 3391, 3320, 3244, 3052, 3022, 2917, 1616, 1583, 1485, 1458, 1447, 1408, 1384,
1321, 1293, 1258, 1224, 814, 782, 763, 752, 742; 1H NMR (400 MHz, CD2Cl2): δ 8.43 (brs, 1H),
8.23 (d, J=7.9 Hz, 1H), 7.44-7.25 (m, 6H), 7.13 (d, J=7.4 Hz, 1H), 6.93-6.88 (m, 2H), 3.73 (brs,
2H), 2.95 (s, 3H); 13C NMR (101 MHz, CD2Cl2): δ 144.6, 140.3, 138.1, 133.3, 131.8, 129.4,
127.1, 125.9, 124.64, 124.58, 123.1, 122.5, 121.9, 120.2, 119.9, 119.3, 116.3, 111.2, 21.0;
HRMS (EI) m/z: [M]+ calcd for C19H16N2 272.1308; found 272.1321. Anal. Calcd: C, 83.79; H,
5.92; N, 10.29; Found: C, 83.60; H, 5.95; N, 10.33.
4.2.2. 2-(4-Ethyl-3-methyl-9H-carbazol-1-yl)aniline (5b)
Was prepared according to the general method from 3-pentanone 4b (1.40 mL) as an off-white
crystalline solid (2.070 g, 52%, 11 d). mp 178-179.5 ˚C (from 2-propanol); Rf = 0.46; IR (KBr,
cm-1): 3396, 3325, 3182, 3088, 3061, 2966, 2936, 2870, 1612, 1504, 1485, 1455, 1393, 1321,
1293, 1264, 881, 758, 740, 633; 1H NMR (500 MHz, (CD3)2SO): δ 10.51 (s, 1H), 8.11 (d, J=8.0
Hz, 1H), 7.52 (d, J=8.1 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.165-7.111 (m, 4H), 6.86 (d, J=8.0 Hz,
1H), 6.71 (t, J=7.4 Hz, 1H), 4.60 (s, 2H), 3.23 (q, J=7.2 Hz, 2H), 2.47 (s, 3H), 1.34 (t, J=7.5 Hz,
13
3H); C NMR (126 MHz, (CD3)2SO): δ 145.6, 140.5, 136.5, 135.5, 130.5, 128.8, 128.2, 125.0,
124.6, 122.9, 122.1, 121.7, 120.9, 119.7, 118.5, 116.5, 115.1, 111.4, 22.7, 18.3, 13.2; HRMS (EI)
m/z: [M]+ calcd for C21H20N2 300.1621; found 300.1635. Anal. Calcd: C, 83.96; H, 6.71; N,
9.33; Found: C, 83.70; H, 6.69; N, 9.32.
4.2.3. 2-(3-Ethyl-4-propyl-9H-carbazol-1-yl)aniline (5c)
17

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Was prepared according to the general method from 4-heptanone 4c (1.80 mL) as an off-white
crystalline solid (2.362 g, 55%, 12 d). mp 132-133.5 ˚C (from 2-propanol); Rf = 0.60; IR (KBr,
cm-1): 3408, 3335, 3204, 3086, 3053, 2963, 2934, 2871, 1615, 1589, 1571, 1500, 1491, 1472,
1452, 1409, 1390, 1320, 1298, 1234, 1156, 1114, 1089, 1077, 1056, 1024, 891, 793, 761, 749,
1
741, 651; H NMR (500 MHz, (CD3)2SO): δ 10.54 (s, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.53 (d,
J=8.0 Hz, 1H), 7.33 (t, J=7.6 Hz, 1H), 7.18-7.14 (m, 4H), 6.88 (d, J=8.1 Hz, 1H), 6.72 (t, J=7.4
Hz, 1H), 4.61 (s, 2H), 3.20-3.17 (m, 2H), 2.82 (q, J=7.5 Hz, 2H), 1.76 (h, J=7.3 Hz, 2H), 1.26 (t,
13
J=7.5 Hz, 3H), 1.18 (t, J=7.3 Hz, 3H); C NMR (126 MHz, (CD3)2SO): δ 145.6, 140.5, 136.3,
133.5, 131.8, 130.6, 128.2, 127.4, 124.5, 123.0, 122.4, 121.6, 121.1, 120.1, 118.5, 116.6, 115.1,
111.5, 31.2, 24.8, 22.8, 16.8, 14.5; HRMS (ESI) m/z: [M+H]+ calcd for C23H24N2 329.2012;
found 329.2025. Anal. Calcd: C, 84.11; H, 7.37; N, 8.53; Found: C, 84.20; H, 7.43; N, 8.61.
4.2.4. 2-(1,2,3,6-Tetrahydrocyclopenta[c]carbazol-5-yl)aniline (5d)
Was prepared according to the general method from cyclopentanone 4d (1.20 mL) as an off-
white crystalline solid (3.633 g, 95%, 1 d). mp 177-178 ˚C (from 2-propanol); Rf = 0.43; IR
(KBr, cm-1): 3439, 3351, 3266, 3048, 2948, 2842, 1603, 1500, 1488, 1450, 1398, 1353, 1325,
1315, 1256, 1024, 894, 748, 741, 734; 1H NMR (500 MHz, (CD3)2SO): δ 10.50 (s, 1H), 8.00 (d,
J=7.8 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.33 (td, J=7.2, 0.9 Hz, 1H), 7.18 (s, 1H), 7.16-7.11 (m,
3H), 6.87 (dd, J=7.8, 0.8 Hz, 1H), 6.72 (td, J=7.4, 1.0 Hz, 1H), 4.61 (s, 2H), 3.39 (t, J=7.4 Hz,
2H), 3.04 (t, J=7.4 Hz, 2H), 2.26 (p, J=7.5 Hz, 2H); 13C NMR (126 MHz, (CD3)2SO): 145.6,
140.3, 136.6, 135.5, 134.2, 130.6, 128.1, 124.8, 123.2, 122.5, 122.4, 121.1, 120.4, 119.1, 118.4,
116.5, 115.1, 111.3, 31.8, 31.5, 25.2; HRMS (EI) m/z: [M]+ calcd for C21H18N2 298.1465; found
298.1475. Anal. Calcd: C, 84.53; H, 6.08; N, 9.39; Found: C, 84.40; H, 6.18; N, 9.32.
18

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
4.2.5. 2-(1,2,3,7-Tetrahydro-1H-benzo[c]carbazol-6-yl)aniline (5e)
Was prepared according to the general method from cyclohexanone 4e (1.40 mL) as an off-white
crystalline solid (3.420 g, 84%, 3 h). mp 180.5-182 ˚C (from 2-propanol); Rf = 0.39; IR (KBr,
cm-1): 3396, 3323, 3160, 3086, 2932, 2856, 2833, 1615, 1507, 1491, 1452, 1399, 1320, 1302,
1
1263, 1158, 757, 740; H NMR (400 MHz, (CD3)2SO): δ 10.29 (s, 1H), 8.12 (d, J=7.6 Hz, 1H),
7.53 (d, J=8.0 Hz, 1H), 7.32 (t, J=7.5 Hz, 1H), 7.18-7.12 (m, 3H), 7.03 (s, 1H), 6.88 (d, J=7.8
Hz, 1H), 6.74 (t, J=7.1 Hz, 1H), 4.45 (s, 2H), 3.34-3.33 (m, 2H), 2.93-2.91 (m, 2H), 2.01-2.00
(m, 2H), 1.90-1.89 (m, 2H); 13C NMR (101 MHz, (CD2)3SO): δ 145.1, 140.0, 135.6, 130.1,
130.0, 127.7, 127.2, 126.6, 123.9, 122.9, 122.8, 121.8, 120.6, 119.6, 117.9, 116.4, 114.9, 110.9,
28.8, 27.0, 22.6 (2 overlapping signals); HRMS (EI) m/z: [M]+ calcd for C22H20N2 312.1621;
found 312.1630. Anal. Calcd: C, 84.58; H, 6.45; N, 8.97; Found: C, 84.32; H, 6.57; N, 8.83.
4.2.6. 2-(1,2,3,4,5,8-Hexahydrocyclohepta[c]carbazol-7-yl)aniline (5f)
Was prepared according to the general method from cycloheptanone 4f (1.50 mL) as an off-
white crystalline solid (2.296 g, 55%, 6 d). mp 188-190 ˚C (from 2-propanol); Rf = 0.51; IR
(KBr, cm-1): 3407, 3335, 3216, 3052, 3027, 2991, 2924, 2848, 1612, 1491, 1452, 1396, 1320,
1
1263, 1229, 1206, 1157, 1122, 754, 737; H NMR (500 MHz, (CD3)2SO): δ 10.48 (s, 1H), 8.26
(d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.31 (td, J=7.2, 1.0 Hz, 1H), 7.16-7.09 (m, 3H), 7.08
(s, 1H), 6.86 (dd, J=7.4, 0.7 Hz, 1H), 6.71 (td, J=7.4, 1.1 Hz, 1H), 4.59 (s, 2H), 3.48 (brs, 2H),
2.97-2.95 (m, 2H), 1.91-1.90 (m, 2H), 1.80 (brs, 2H), 1.68 (brs, 2H); 13C NMR (126 MHz,
(CD3)2SO): δ 145.6, 140.7, 136.7, 136.4, 134.0, 130.6, 128.1, 127.8, 124.6, 122.9, 122.7, 121.9,
120.8, 119.0, 118.2, 116.5, 115.1, 111.5, 35.1. 32.1, 30.0, 28.4, 26.7; HRMS (EI) m/z: [M]+ calcd
19

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
for C23H22N2 326.1778; found 326.1786. Anal. Calcd: C, 84.63; H, 6.79; N, 8.58; Found: C,
84.59; H, 6.79; N, 8.51.
4.2.7. 2-(2,3,4,5,6,9-Hexahydro-1H-cycloocta[c]carbazol-8-yl)aniline (5g)
Was prepared according to the general method from cyclooctanone 4g (1.660 g) as an off-white
crystalline powder (1.901 g, 43%, 10 d). mp 133-134 ˚C (from 2-propanol). Rf = 0.48; IR (KBr,
1
cm-1): 3412, 3052, 3025, 2918, 2488, 1613, 1453, 1259, 1072, 1024, 738, 618; H NMR (500
MHz, (CD3)2SO): δ 10.54 (s, 1H), 8.12 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.32 (td,
J=7.3, 0.7 Hz, 1H), 7.17-7.12 (m, 3H), 7.08 (s, 1H), 6.87 (d, J=7.7 Hz, 1H), 6.72 (td, J=7.4, 1.0
Hz, 1H), 4.59 (s, 2H), 3.38 (brs, 2H), 2.94-2.92 (m, 2H), 1.91-1.89 (m, 2H), 1.69 (brs, 2H), 1.45
(brs, 2H), 1.33 (brs, 2H); 13C NMR (126 MHz, CD2Cl2): δ 144.5, 140.7, 137.2, 135.7, 134.0,
131.7, 129.3, 128.9, 125.6, 124.9, 124.2, 123.1, 121.8, 120.1, 119.8, 119.3, 116.2, 111.2, 33.7,
33.2, 29.7, 28.2, 27.1, 26.7; HRMS (EI) m/z: [M]+ calcd for C24H24N2 340.1934; found 340.1932.
Anal. Calcd: C, 84.67; H, 7.11; N, 8.23; Found: C, 84.52; H, 7.07; N, 8.19.
4.2.8. 2-(1,2,3,4,5,6,7,10-Octahydrocyclonona[c]carbazol-9-yl)aniline (5h)
Was prepared according to the general method from cyclononanone 4h (1.89 mL) as an off-
white crystalline solid (2.036 g, 44%, 14 d). mp 155-157 ˚C (from 2-propanol); Rf = 0.47; IR
(KBr, cm-1): 3428, 3347, 3228, 3088, 3055, 3025, 2974, 2925, 2865, 2850, 1611, 1588, 1482,
1
1450, 1391, 1322, 1308, 1260, 1157, 1024, 1000, 901, 756, 742, 618; H NMR (500 MHz,
(CD3)2SO):j δ 10.57 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.32 (td, J=7.2, 0.8
Hz, 1H), 7.17-7.13 (m, 3H), 7.07 (s, 1H), 6.87 (d, J=7.5 Hz, 1H), 6.72 (td, J=7.4, 1.1 Hz, 1H),
4.59 (s, 2H), 3.39-3.37 (m, 2H), 2.94-2.92 (m, 2H), 1.96 (brs, 2H), 1.72 (brs, 2H), 1.47-1.33 (m,
20

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
13
6H); C NMR (126 MHz, (CD3)2SO): δ 145.5, 140.4, 136.3, 134.5, 131.9, 130.6, 128.3, 128.2,
124.5, 122.9, 122.5, 121.8, 120.5, 120.2, 118.5, 116.6, 115.1, 111.4, 32.1, 29.4, 28.3 27.2, 26.3,
24.3, 24.2; HRMS (EI) m/z: [M]+ calcd for C25H26N2 354.2091; found 354.2098. Anal. Calcd: C,
84.70; H, 7.44; N, 7.89; Found: C, 84.31; H, 7.44; N, 7.89.
4.2.9. 2-(2,3,4,5,6,7,8,11-Octahydro-1H-cyclodeca[c]carbazol-10-yl)aniline (5i)
Was prepared according to a scaled-down adaptation of the general method from cyclodecanone
4i (1.00 mL) as an off-white crystalline powder (1.103 g, 45%, 13 d). mp 143-145 ˚C (from
EA:hexane); Rf = 0.49; IR (KBr, cm-1): 3427, 3347, 3225, 3053, 3001, 2920, 2848, 1920, 1885,
1793, 1613, 1587, 1499, 1480, 1451, 1392, 1336, 1310, 1263, 1160, 1024, 903, 758, 739, 653;
1H NMR (500 MHz, (CD3)2SO): δ 10.58 (s, 1H), 8.11 (d, J=8.0 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H),
7.31 (td, J=7.3, 0.8 Hz, 1H), 7.18-7.13 (m, 4H), 6.87 (d, J=7.6 Hz, 1H), 6.73 (td, J=7.4, 1.1 Hz,
1H), 4.59 (s, 2H), 3.44 (t, J=6.3 Hz, 2H), 3.02 (brs, 2H), 1.95 (brs, 4H), 1.57 (brs, 2H), 1.45 (brs,
2H), 1.30 (brs, 2H), 1.05 (brs, 2H); 13C NMR (126 MHz, (CD3)2SO): δ 145.5, 140.3, 136.0,
133.3, 130.53, 130.51, 128.2, 126.9, 124.3, 122.9, 122.4, 122.2, 120.7, 120.4, 118.4, 116.6,
115.1, 111.5, 29.7, 28.8, 27.9, 25.6, 25.4, 24.8, 21.5, 20.8; HRMS (ESI) m/z: [M+H]+ calcd for
C26H28N2 369.2325; found 369.2327. Anal. Calcd: C, 84.74; H, 7.66; N, 7.60; Found: C, 84.66;
H, 7.71; N, 7.67.
4.2.10. 2-(1,2,3,4,5,6,7,8,9,12-Decahydrocycloundeca[c]carbazol-11-yl)aniline (5j)
Was prepared according to the general method from cycloundecanone 4j (2.40 mL) as an off-
white crystalline solid (1.324 g, 27%, 14 d). mp 185-187 ˚C (from 2-propanol); Rf = 0.55; IR
(KBr, cm-1): 3421, 3344, 3215, 3056, 2865, 2842, 1614, 1589, 1499, 1480, 1451, 1394, 1324,
21

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
1
1298, 1261, 1160, 1119, 1029, 890, 741; H NMR (500 MHz, (CD3)2SO): δ 10.55 (s, 1H), 8.07
(d, J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.32 (t, J=7.3 Hz, 1H), 7.17-7.13 (m, 4H), 6.87 (d,
J=7.5 Hz, 1H), 6.73 (td, J=7.4, 1.0 Hz, 1H), 4.58 (s, 2H), 3.33-3.31 (m, 2H), 2.93 (t, J=6.7 Hz,
2H), 1.96 (brs, 2H), 1.80 (p, J=6.6 Hz, 2H), 1.61 (brs, 2H), 1.49 (brs, 2H), 1.43-1.38 (m, 2H),
1.22 (brs, 4H); 13C NMR (126 MHz, (CD3)2SO): δ 145.5, 140.4, 136.1, 135.4, 130.5, 130.0,
128.2, 126.7, 124.4, 123.0, 122.4, 122.0, 121.2, 119.8, 118.4, 116.6, 115.1, 111.4, 28.4, 28.3,
27.6, 27.3, 26.4, 24.7, 24.3, 23.8, 23.3; HRMS (EI) m/z: [M]+ calcd for C27H30N2 382.2402;
found 382.2412. Anal. Calcd: C, 84.77; H, 7.90; N, 7.32; Found: C, 84.60; H, 8.04; N, 7.35.
4.2.11. 2-(2,3,4,5,6,7,8,9,10,13-Decahydro-1H-cyclododeca[c]carbazol-12-yl)aniline (5k)
Was prepared according to the general method from cyclododecanone 4k (2.342 g) as an off-
white crystalline solid (2.477 g, 48%, 14 d). mp 177-178 ˚C (from 2-propanol); Rf = 0.43; IR
(KBr, cm-1): 3416, 3341, 3221, 3064, 2922, 2857, 2845, 1614, 1589, 1499, 1478, 1450, 1391,
1
1323, 1299, 1262, 1157, 750, 741; H NMR (500 MHz, (CD3)2SO): δ 10.54 (s, 1H), 8.05 (d,
J=8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.32 (t, J=7.4 Hz, 1H), 7.17-7.13 (m, 4H), 6.87 (d, J=7.5
Hz, 1H), 6.72 (td, J=7.4, 0.9 Hz, 1H), 4.61 (s, 2H), 3.29 (t, J=7.3 Hz, 2H), 2.80 (brs, 2H), 1.92
(brs, 2H), 1.77 (brs, 2H), 1.68 (brs, 2H), 1.60 (brs, 2H), 1.54-1.38 (m, 8H); 13C NMR (126 MHz,
(CD3)2SO): δ 145.5, 140.4, 136.1, 133.7, 131.0, 130.6, 128.2, 128.1, 124.4, 122.9, 122.3, 121.9,
121.2, 120.1, 118.5, 116.6, 115.2, 111.5, 29.9, 28.7, 27.3, 26.8, 26.35, 26.33, 26.0, 24.7, 22.5,
21.5; HRMS (EI) m/z: [M]+ calcd for C28H32N2 396.2560; found 396.2567. Anal. Calcd: C,
84.80; H, 8.13; N, 7.06; Found: C, 84.62; H, 8.26; N, 7.12.
4.2.12. 2-(4-Phenyl-9H-carbazol-1-yl)aniline (5l)
22

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
Was prepared according to the general method from acetophenone 4l (1.50 mL) as a white
crystalline powder (3.884 g, 87%, 3 d). mp 136-138 ˚C (from DCM:hexane); Rf = 0.46; IR (KBr,
cm-1): 3395, 3325, 3165, 3058, 3031, 2901, 2819, 1614, 1578, 1482, 1457, 1378, 1322, 1306,
1270, 1123, 821, 751, 742, 700, 652, 617; 1H NMR (500 MHz, (CD3)2SO): δ 10.79 (s, 1H), 7.64-
7.63 (m, 2H), 7.60-7.57 (m, 2H), 7.54-7.50 (m, 2H), 7.35 (d, J=7.5 Hz, 2H), 7.29 (td, J=7.1, 1.0
Hz, 1H), 7.20-7.17 (m, 2H), 7.08 (d, J=7.4 Hz, 1H), 6.91-6.88 (m, 2H), 6.75 (td, J=7.4, 1.0 Hz,
13
1H), 4.72 (s, 2H); C NMR (126 MHz, (CD3)2SO): δ 145.7, 140.9, 140.4, 137.9, 135.7, 130.6,
128.9, 128.50, 128.45, 127.5, 126.2, 125.2, 122.5, 121.9, 121.7, 121.2, 120.3, 119.9, 118.1,
116.6, 115.3, 111.6; HRMS (EI) m/z: [M]+ calcd for C24H18N2 334.1465; found 334.1477. Anal.
Calcd: C, 86.20; H, 5.43; N, 8.38; Found: C, 86.02; H, 5.54; N, 8.38.
4.2.13. 2-(4-(4-Methylphenyl)-9H-carbazol-1-yl)aniline (5m)
Was prepared according to the general method from 4-methylacetophenone 4m (1.75 mL) as an
o
off-white crystalline powder (1.892 g, 42%, 6 d). mp 114-116 C (from EA:hexane); Rf = 0.51;
IR (KBr, cm-1): 3416, 3386, 3052, 3023, 2919, 1613, 1577, 1560, 1502, 1489, 1456, 1393, 1376,
1321, 1304, 1266, 1122, 1021, 1002, 814, 752, 739; 1H NMR (500 MHz, (CD3)2SO): δ 10.78 (s,
1H), 7.55-7.52 (m, 3H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (d, J=7.8 Hz, 2H), 7.34 (d, J=7.4 Hz, 1H),
7.28 (td, J=7.2, 1.0 Hz, 1H), 7.20-7.17 (m, 2H), 7.06 (d, J=7.4 Hz, 1H), 6.93-6.90 (m, 2H), 6.75
(td, J=7.0, 0.7 Hz, 1H), 4.71 (s, 2H), 2.45 (s, 3H); 13C NMR (126 MHz, (CD3)2SO): δ 145.7,
140.4, 138.0, 137.9, 136.7, 135.7, 130.6, 129.1, 128.8, 128.4, 126.2, 125.2, 122.5, 122.0, 121.5,
121.2, 120.3, 120.0, 118.1, 116.6, 115.3, 111.6, 20.9; HRMS (ESI) m/z: [M+H]+ calcd for
C25H20N2 349.1699; found 349.1690. Anal. Calcd: C, 86.17; H, 5.79; N, 8.04; Found: C, 86.21;
H, 5.75; N, 8.11.
23

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
4.2.14. 2-(4-(4-Aminophenyl)-9H-carbazol-1-yl)aniline (5n)
Prepared according to the general method from 4-aminoacetophenone 4n (0.586 g) as a brown
crystalline powder, which contained residual 4n (5 mol%) that could not be removed (1.397 g,
1
o
92%; 95 mol%, calculated by H NMR analysis; 5 d). mp 133-134 C (from EA:hexane); Rf =
0.10; IR (KBr, cm-1): 3455, 3373, 3215, 3056, 3027, 1617, 1578, 1561, 1528, 1503, 1484, 1456,
1
1376, 1321, 1306, 1269, 1178, 1123, 819, 754; H NMR (500 MHz, (CD3)2SO): δ 10.68 (s, 1H),
7.59 (d, J=8.0 Hz, 1H), 7.51 (d, J=8.1 Hz, 1H), 7.30-7.26 (m, 4H), 7.18-7.15 (m, 2H), 7.01 (d,
J=7.4 Hz, 1H), 6.94-6.88 (m, 2H), 6.76-6.72 (m, 3H), 5.26 (s, 2H), 4.68 (s, 2H); 13C NMR (126
MHz, (CD3)2SO): δ 148.2, 145.7, 140.3, 137.9, 136.7, 130.6, 129.5, 128.3, 128.1, 126.2, 124.9,
122.7, 122.4, 121.5, 120.6, 120.2, 120.1, 117.9, 116.6, 115.2, 113.8, 111.4; HRMS (ESI) m/z:
[M+H]+ calcd for C24H19N3 350.1652; found 350.1661.
4.2.15. 4-(1-(2-Aminophenyl)-9H-carbazol-4-yl)phenol (5o)
Was prepared according to the general method from 4-hydroxyacetophenone 4o (0.580 g) as a
o
brown crystalline powder (1.151 g, 76%, 5 d). mp 236-238 C (from EA:hexane); Rf = 0.31; IR
(KBr, cm-1): 3411, 3331, 3059, 2784, 1611, 1578, 1529, 1502, 1484, 1456, 1381, 1320, 1306,
1
1261, 1229, 1169, 1122, 1100, 826, 793, 750, 730; H NMR (500 MHz, (CD3)2SO): δ 10.73 (s,
1H), 9.61 (s, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.44 (d, J=8.0 Hz, 2H), 7.33-
7.27 (m, 2H), 7.20-7.17 (m, 2H), 7.04 (d, J=7.3 Hz, 1H), 6.98-6.90 (m, 4H), 6.75 (t, J=7.2 Hz,
13
1H), 4.70 (s, 2H); C NMR (126 MHz, (CD3)2SO): δ 156.9, 145.7, 140.4, 137.9, 136.0, 131.5,
130.6, 130.0, 128.4, 126.2, 125.1, 122.6, 122.2, 121.3, 121.1, 120.3, 120.2, 118.0, 116.6, 115.28,
24

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
115.26, 111.5; HRMS (ESI) m/z: [M+H]+ calcd for C24H18N2O 351.1492; found 351.1480. Anal.
Calcd: C, 82.26; H, 5.18; N, 7.99; Found: C, 82.44; H, 5.19; N, 8.01.
4.2.16. 2-(4-(4-Methoxyphenyl)-9H-carbazol-1-yl)aniline (5p)
Was prepared according to the general method from 4-methoxyacetophenone 4p (0.650 g) as an
o
off-white crystalline powder (0.868 g, 53%, 4 d). mp 107-109 C (from EA:hexane); Rf = 0.34;
IR (KBr, cm-1): 3415, 3375, 3061, 3029, 2998, 2962, 2930, 2903, 2826, 1610, 1525, 1502, 1488,
1
1457, 1376, 1304, 1244, 1174, 1031, 821, 741; H NMR (500 MHz, (CD3)2SO): δ 10.78 (s, 1H),
7.57-7.55 (m, 3H), 7.46 (d, J=8.0 Hz, 1H), 7.34 (d, J=7.4 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H), 7.20-
7.17 (m, 2H), 7.14 (d, J=7.8 Hz, 2H), 7.06 (d, J= 7.4 Hz, 1H), 6.94-6.91 (m, 2H), 6.75 (t, J=7.2
Hz, 1H), 4.72 (s, 2H), 3.87 (s, 3H); 13C NMR (126 MHz, (CD3)2SO): δ 158.8, 145.7, 140.4,
137.9, 135.5, 133.1, 130.6, 130.1, 128.4, 126.3, 125.2, 122.6, 122.1, 121.4, 121.3, 120.4, 120.1,
118.1, 116.6, 115.3, 113.9, 111.6, 55.2; HRMS (EI) m/z: [M]+ calcd for C25H20N2O 364.1570;
found 364.1577. Anal. Calcd: C, 82.39; H, 5.53; N, 7.69; Found: C, 82.16; H, 5.53; N, 7.54.
4.2.17. 2-(4-(4-Chlorophenyl)-9H-carbazol-1-yl)aniline (5q)
Was prepared according to the general method from 4-chloroacetophenone 4q (0.56 mL) as a
brown crystalline powder (1.373 g, 86%, 4 d). mp 138-139.5 oC (from EA:hexane); Rf = 0.45; IR
(KBr, cm-1): 3414, 3339, 3199, 3056, 3025, 2917, 2813, 1612, 1528, 1491, 1457, 1376, 1322,
1
1305, 1124, 1096, 1014, 767, 741; H NMR (500 MHz, (CD3)2SO): δ 10.85 (s, 1H), 7.67-7.62
(m, 4H), 7.57 (d, J=8.2 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.4 Hz, 1H), 7.31 (ddd,
J=8.2, 7.0, 1.2 Hz, 1H), 7.21-7.18 (m, 2H), 7.08 (d, J=7.4 Hz, 1H), 6.97-6.91 (m, 2H), 6.75 (td,
13
J=7.4, 1.2 Hz, 1H), 4.72 (s, 2H); C NMR (126 MHz, (CD3)2SO): δ 145.7, 140.5, 139.7, 137.9,
25

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
134.2, 132.3, 130.7, 130.5, 128.6, 128.5, 126.3, 125.3, 122.3, 122.1, 121.7, 121.1, 120.3, 119.8,
118.3, 116.6, 115.3, 111.7; HRMS (EI) m/z: [M]+ calcd for C24H17ClN2 368.1075; found
368.1080. Anal. Calcd: C, 78.15; H, 4.65; Cl, 9.61; N, 7.59; Found: C, 78.04; H, 4.66; Cl, 9.54;
N, 7.63.
4.2.18. 2-(4-(4-Bromophenyl)-9H-carbazol-1-yl)aniline (5r)
Was prepared according to the general method from 4-bromoacetophenone 4r (0.851 g) as an
o
off-white crystalline powder (1.501 g, 82%, 3 d). mp 128-130 C (from EA:hexane); Rf = 0.40;
IR (KBr, cm-1): 3421, 3056, 3020, 1615, 1518, 1480, 1456, 1375, 1321, 1305, 1123, 1096, 1069,
1
1011, 817, 752, 740; H NMR (500 MHz, (CD3)2SO): δ 10.86 (s, 1H), 7.77 (d, J=7.4 Hz, 2H),
7.60-7.56 (m, 3H), 7.40 (d, J=8.0 Hz, 1H), 7.36 (d, J=7.1 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 7.20-
7.18 (m, 2H), 7.07 (d, J=7.1 Hz, 1H), 6.97-6.91 (m, 2H), 6.75 (t, J=7.3 Hz, 1 H), 4.73 (s, 2H);
13C NMR (126 MHz, (CD3)2SO): δ 145.7, 140.5, 140.1, 137.9, 134.3, 131.5, 131.1, 130.6, 128.5,
126.3, 125.4, 122.3, 122.2, 121.7, 121.1, 120.9, 120.3, 119.7, 118.3, 116.6, 115.3, 111.8; HRMS
(EI) m/z: [M]+ calcd for C24H17Br79N2 412.0570; found 412.0580. Anal. Calcd: C, 69.74; H,
4.15; Br, 19.33; N, 6.78; Found: C, 69.68; H, 4.19; Br, 19.21; N, 6.71.
4.2.19. 2-(3-Methyl-4-phenyl-9H-carbazol-1-yl)aniline (5s)
Was prepared according to the general method from propiophenone 4s (1.72 mL) as a white
crystalline powder (2.925 g, 65%, 3 d). mp 220-221.5 ˚C (from DCM:hexane); Rf = 0.45; IR
(KBr, cm-1): 3393, 3321, 3171, 3056, 3029, 2980, 2921, 1616, 1573, 1492, 1453, 1388, 1377,
1341, 1318, 1299, 1241, 1160, 1074, 1034, 881, 747, 703, 625; 1H NMR (500 MHz, (CD3)2SO):
δ 10.62 (s, 1H), 7.61 (t, J=7.4 Hz, 2H), 7.55-7.52 (m, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.42-7.40 (m,
26

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
2H), 7.25 (s, 1H), 7.22-7.16 (m, 3H), 6.90 (d, J=8.0 Hz, 1H), 6.77-6.73 (m, 2H), 6.61 (d, J=8.0
Hz, 1H), 4.71 (s, 2H), 2.21 (s, 3H); 13C NMR (126 MHz, (CD3)2SO): δ 145.7, 140.5, 140.2,
136.0, 134.4, 130.6, 129.0, 128.9, 128.4, 128.3, 127.3, 125.1, 124.8, 122.7, 122.3, 121.5, 121.3,
121.0, 117.9, 116.6, 115.2, 111.4, 19.2; HRMS (EI) m/z: [M]+ calcd for C25H20N2 348.1621;
found 348.1623. Anal. Calcd: C, 86.17; H, 5.79; N, 8.04; Found: C, 86.06; H, 7.61; N, 8.07.
4.2.20. 2-(4-(2,3,4-Trichlorophenyl)-9H-carbazol-1-yl)aniline (5t)
Was prepared according to the general method from 2,3,4-trichloroacetophenone 4t (0.945 g) as
a pink crystalline powder (1.764 g, 93%, 3 d). mp 150.5-152 oC (from EA:hexane); Rf = 0.40; IR
(KBr, cm-1): 3424, 3384, 3061, 3029, 1726, 1617, 1490, 1439, 1383, 1358, 1321, 1305, 1254,
1187, 1155, 1124, 816, 796, 752; 1H NMR (500 MHz, (CD3)2SO): δ 10.91 (s, 1H), 7.85 (d, J=8.0
Hz, 1H), 7.55 (t, J=7.2 Hz, 2H), 7.40 (d, J=7.4 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 7.22-7.18 (m,
2H), 7.08 (d, J=7.4 Hz, 1H), 6.97- 6.88 (m, 3H), 6.76 (t, J=7.3 Hz, 1H), 4.71 (s, 2H); 13C NMR
(126 MHz, (CD3)2SO): δ 145.7, 140.6, 140.4, 137.5, 132.9, 132.4, 131.1, 130.7, 130.5, 130.4,
129.1, 128.6, 126.1, 125.6, 122.8, 122.2, 121.6, 120.4, 120.2, 119.9, 118.8, 116.7, 115.4, 111.8;
HRMS (EI) m/z: [M]+ calcd for C24H15Cl3N2 436.0295; found 436.0302. Anal. Calcd: C, 65.85;
H, 3.45; Cl, 24.29; N, 6.40; Found: C, 65.61; H, 3.52; Cl, 24.04; N, 6.23.
4.2.21. 2-(4-(2,5-Dimethoxyphenyl)-9H-carbazol-1-yl)aniline (5u)
Was prepared according to the general method from 2,5-dimethoxyacetophenone 4u (0.70 mL)
o
as a pink crystalline solid (1.388 g, 81%, 3 d). mp 132-133 C (from EA:hexane); Rf = 0.35; IR
(KBr, cm-1): 3416, 3377, 3065, 3029, 2998, 2939, 2899, 2836, 1616, 1492, 1458, 1416, 1377,
1
1319, 1265, 1221, 1178, 1083, 1045, 822, 744; H NMR (500 MHz, (CD3)2SO): δ 10.73 (s, 1H),
27

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
7.52 (d, J=8.1 Hz, 1H), 7.35 (d, J=7.3 Hz, 1H), 7.28 (t, J=7.5 Hz, 1H), 7.23-7.18 (m, 2H), 7.16-
7.11 (m, 2H), 7.08-7.06 (m, 2H), 6.94-6.89 (m, 3H), 6.77 (t, J=7.3 Hz, 1H), 4.71 (s, 2H), 3.76 (s,
13
3H), 3.57 (s, 3H); C NMR (126 MHz, (CD3)2SO): δ 153.1, 150.9, 145.7, 140.3, 137.4, 132.0,
130.6, 130.4, 128.4, 125.9, 125.1, 122.7, 122.5, 121.5, 121.08, 121.05, 120.6, 118.2, 116.7,
116.5, 115.3, 113.6, 112.3, 111.4, 55.7, 55.4; HRMS (EI) m/z: [M]+ calcd for C26H22N2O2
394.1676; found 394.1685. Anal. Calcd: C, 79.17; H, 5.62; N, 7.10; Anal. Calcd for [C26H22N2O2
. 0.16 mol% EA]: C, 78.32; H, 5.74; N, 6.86; Found: C, 78.37; H, 5.69; N, 7.01.
4.2.22. 2-(4-(Thiophen-2-yl)-9H-carbazol-1-yl)aniline (5v)
Was prepared according to the general method from 2-acetylthiophene 4v (0.47 mL) as a pink
crystalline solid (1.064 g, 72%, 2 d). mp 91-93˚C (from EA:hexane); Rf = 0.56; IR (KBr, cm-1):
3411, 3059, 2922, 2852, 1613, 1577, 1566, 1507, 1489, 1456, 1423, 1380, 1319, 1299, 1253,
1219, 1155, 1122, 1088, 1070, 1002, 843, 820, 788, 752, 701; 1H NMR (500 MHz, (CD3)2SO): δ
10.85 (s, 1H), 7.73 (dd, J=5.1, 1.2 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.56 (d, J=8.1 Hz, 1H), 7.39
(dd, J=3.4, 1.3 Hz, 1H), 7.35-7.30 (m, 3H), 7.21-7.17 (m, 3H), 6.98 (ddd, J=8.1, 7.0, 1.1 Hz,
1H), 6.91 (dd, J=8.6, 1.3 Hz, 1H), 6.75 (td, J=7.3, 1.3 Hz, 1H), 4.74 (s, 2H); 13C NMR (126
MHz, (CD3)2SO): δ 145.7, 141.8, 140.4, 137.9, 130.5, 128.6, 127.7, 127.6, 126.6, 126.2, 126.1,
125.5, 122.8, 122.2, 121.8, 121.5, 121.2, 120.7, 118.3, 116.6, 115.3, 111.7; HRMS (ESI) m/z:
[M+H]+ calcd for C22H16N2S 341.1107; found 341.1105.
4.2.23. 2-(4-(Pyridin-2-yl)-9H-carbazol-1-yl)aniline (5w)
Was prepared according to the general method from 2-acetylpyridine 4w (0.49 mL) as an orange
microcrystalline solid (0.536 g, 36%, 2 d). mp 130-132 ˚C (from EA:hexane); Rf = 0.09; IR
28

ACCEPTED MANUSCRIPT
Tetrahedron Manuscript
(KBr, cm-1): 3422, 3054, 2925, 1654, 1637, 1617, 1587, 1570, 1560, 1522, 1508, 1490, 1468,
1
1457, 1429, 1379, 1322, 1268, 1222, 1154, 1127, 1104, 1002, 779, 745; H NMR (500 MHz,
(CD3)2SO): δ 10.81 ( s, 1H), 8.81 (dq, J=4.8, 0.9 Hz, 1H), 8.01 (td, J=7.7, 1.8 Hz, 1H), 7.77 (d,
J=7.8 Hz, 1H), 7.54-7.48 (m, 3H), 7.38 (d, J=7.5 Hz, 1H), 7.30 (ddd, J=8.2, 7.0, 1.2 Hz, 1H),
7.26 (d, J=7.5 Hz, 1H), 7.21-7.18 (m, 2H), 6.94-6.90 (m, 2H), 6.76 (td, J=7.4, 1.2 Hz, 1H), 4.71
(s, 2H); 13C NMR (126 MHz, (CD3)2SO): δ 159.0, 149.3, 145.7, 140.5, 138.0, 136.8, 134.9,
130.5, 128.6, 126.1, 125.4, 124.0, 122.7, 122.6, 122.4, 122.2, 121.8, 120.6, 120.1, 118.1, 116.6,
115.3, 111.6; HRMS (ESI) m/z: [M+H]+ calcd for C23H17N3 336.1495; found 336.1509.
4.2.24. 2-(5,8-Dihydroindeno[2,1-c]carbazol-6-yl)aniline (5x)
Was prepared according to the general method from 1-indanone 4x (1.710 g) as a white
microcrystalline powder (3.109 g, 69%, 3 d). mp 204-206 ˚C (from 2-propanol); Rf = 0.40; IR
(KBr, cm-1): 3404, 3317, 3060, 2966, 2881, 1609, 1499, 1487, 1451, 1400, 1371, 1324, 1295,
1
1238, 1160, 1020, 944, 881, 757, 738, 670; H NMR (500 MHz, (CD3)2SO): δ 10.75 (s, 1H),
8.17 (d, J=7.8 Hz, 1H), 7.91 (d, J=7.5 Hz, 1H), 7.85 (s, 1H), 7.67 (d, J=7.4 Hz, 1H), 7.57 (d,
J=8.1 Hz, 1H), 7.41 (td, J=8.1, 1.0 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.26-7.19 (m, 4H), 6.91 (d,
J=7.7 Hz, 1H), 6.77 (td, J=7.4, 1.1 Hz, 1H), 4.69 (s, 2H), 4.37 (s, 2H); 13C NMR (126 MHz,
(CD3)2SO): δ 145.8, 142.4, 142.3, 140.5, 137.4, 135.4, 132.9, 130.7, 128.4, 126.7, 125.4, 125.1,
124.9, 122.9, 122.3, 121.6, 121.4, 119.5, 119.1, 118.9, 118.6, 116.5, 115.1, 111.6, 35.7; HRMS
(EI) m/z: [M]+ calcd for C25H18N2 346.1465; found 346.1471. Anal. Calcd: C, 86.68; H, 5.24; N,
8.09; Found: C, 86.66; H, 5.14; N, 8.12.
4.2.25. 2-(6,9-Dihydro-5H-naphtho[2,1-c]carbazol-8-yl)aniline (5y)
29