Oxidative Coupling of Carbazoles: A Substituent-Governed Regioselectivity Profile

Article abstract of DOI:10.1021/acs.joc.8b02322

Oxidative C-C coupling of carbazoles possessing various substituents is demonstrated in the presence of organic (metal-free) recyclable oxidants, such as DDQ or CA/H⁺, for accessing bicarbazole regioisomers. Differently substituted carbazoles are examined to showcase regioselective discrimination (3,3′-versus 1,3′-bicarbazoles) and preferences based on sterics and electronics in oxidative coupling. Finally, a mechanism that involves the carbazole radical cation has been traced (evidenced) and proposed on the basis of the UV-vis-NIR absorption and EPR spectroscopy results. This study underlines the strategic chemical preparation of a series of bicarbazoles in an efficient manner.

Full text of DOI:10.1021/acs.joc.8b02322

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Article
Oxidative Coupling of Carbazoles: A
Substituent-Governed Regioselectivity Profile
Sudesh Mallick, Sudhakar Maddala, Kalidass Kollimalayan, and Parthasarathy Venkatakrishnan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02322 • Publication Date (Web): 06 Dec 2018
Downloaded from http://pubs.acs.org on December 7, 2018
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Oxidative Coupling of Carbazoles: A Substituent-Governed Regioselectivity Profile
Sudesh Mallick, Sudhakar Maddala, Kalidass Kollimalayan and
Parthasarathy Venkatakrishnan*
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Department of Chemistry, Indian Institute of Technology Madras, Chennai – 600 036,
Tamil Nadu, INDIA
pvenkat@iitm.ac.in
-
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ABSTRACT
R1
R
1
R = EDG
N
3
3
'
R1
Oxidative
C-C coupling
N
3
R
R1
DDQ/CA
MSA:DCM
R1
N
R
3'
R1
1
R = Alkyl/Aryl
N
1
R = EWG
N
R
R
Oxidative C–C coupling of carbazoles possessing various substituents are demonstrated, in
+
presence of organic (metal-free) recyclable oxidants, such as, DDQ or CA/H for accessing
bicarbazole regioisomers. Differently substituted carbazoles are examined to showcase
regioselectivity discrimination (3,3'- versus 1,3'-bicarbazoles), and preferences based on
sterics and electronics in oxidative coupling. Finally, a mechanism that involves carbazole
radical cation has been traced (evidenced) and proposed based on the UV-vis-NIR absorption
and EPR spectroscopy results. This study underlines the strategic chemical preparation of a
series of bicarbazoles in an efficient manner.
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Introduction
Carbazoles (Cz) — 2,2'-connected diphenylamines — are inextricable heteroaromatic
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skeletons in the fields of organic, medicinal and polymer chemistry. Very importantly,
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bicarbazoles (BCz) are found to showcase potential application in organic electronics and
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photonics, sensing and memory devices because of their advantageous/exemplary
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characteristics, such as, low ionization potentials, excellent glassy nature (T ) and blue
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luminescence, etc. In particular, they have been identified as important bio-skeletons in
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several natural products. For example, BCz is an excellent host material for high-efficiency
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d,8
phosphorescent OLEDs
and bismahanine is a naturally occurring alkaloid showing
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excellent biological activity (Chart 1).
Chart 1.
Syntheses of bicarbazoles have always been achieved by transition metal-based C–C
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coupling reactions which are most often limited due to the following reasons: (i) catalysts
and ligands used are expensive, (ii) high temperatures, strong bases and long reaction
duration are inevitable, (iii) dehalogenation and homocoupling are commonly observed side
reactions, and (iv) contamination of metal impurities with the isolated products in trace
amounts. Especially, the presence of metal impurities in final products hampers their
performance in electronic devices and introduces toxicity in biological studies. The other
commonly exploited method to introduce C–C bond between electron rich arene carbazole is
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the oxidative coupling. Generally, this approach leads to several side products (oligomers,
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higher oligomers or polymers) through possible active sites. Hence this approach mostly
relies on blocking of the active sites by substituents appropriately, and as a consequence, a
thorough understanding of this reaction is deemed necessary. A careful literature survey
revealed that the oxidative coupling of carbazoles (often with electron donating substituents)
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12a-d
12e-g
is mainly based on either metal salts
or halogen-containing agents
(Scheme 1a),
while only a few reports exist on the utility of organic oxidants for the synthesis of
bicarbazoles under harsh conditions, and that too only after blocking the active sites
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appropriately. In continuation to our interest in the rapid synthesis of interesting hole-
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transporting materials, we have recently reported a quinone-based recyclable organic
oxidant (metal-free) for an economic, efficient and simple synthesis of
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tetrarylaminobiaryls/diarylaminobiaryls starting from diaryl/triarylamines. Expanding this
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idea further, we envisioned that N-phenylcarbazoles (Eox = 1.24 V vs SCE) that are more
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planar and conjugated than triphenylamines (TPA, Eox = 0.97 V vs SCE) may also undergo
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oxidative C–C coupling under chloranil (CA, Ered = 0.02 V vs SCE) or 2,3-dichloro-5,6-
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dicyano-1,4-benzoquinone (DDQ, Ered = 0.60 V vs SCE) in presence of organic acids
(organic oxidants) to yield bicarbazoles via a possible electron transfer. We also questioned
the effect of substituents and sterics on the reactivity and regioselectivity in the oxidative
coupling of carbazoles.
Thus, in this paper, we have reported the oxidative synthesis of 3,3'-bicarbazole as well as
1
,3'-bicarbazole/1,1'-bicarbazole simply by changing the electronic nature (electron donating
or electron withdrawing) of substituents on precursor carbazole using quinone-based organic
recyclable oxidants (Scheme 1b). Moreover, we have thoroughly investigated the influence of
sterics/electronics on the coupling and regioselectivity, compatibility of various functional
groups, and the efficiency of the organic oxidants (DDQ/CA) in the oxidative coupling
reaction of carbazoles. Such a chemical synthesis of bicarbazoles by tuning the nature of
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substituents, and investigation of the regioselectivity/steric aspects of chemical oxidative
coupling of carbazoles has been heretofore unreported. Further, based on UV-vis-NIR
absorption and EPR spectroscopic studies and previous reports, it is shown that the
mechanism of formation of bicarbazoles involves a radical cation pathway. Most importantly,
the synthesized bicarbazoles can be structurally elaborated further, if need be, to arrive at a
gamut of functional organic materials of interest and various carbazole-based natural
products.
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Scheme 1. Conditions explored for the oxidative coupling of carbazoles in the literature and
in this report.
Results and Discussion
Initially, the reaction conditions for the oxidative coupling were optimized with the
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commercially available N-ethylcarbazole 1a (Eox = 1.12 V vs SCE). The results are
consolidated in Table 1 (see SI for complete optimization details). Among various organic
oxidants screened, DDQ and chloranil (CA) provided the oxidative coupling product in near
quantitative yields. The best optimized condition for the oxidative coupling is: N-
ethylcarbazole (0.8 mmol), DDQ/CA (1.6 mmol), and methanesulphonic acid
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(
MSA):dichloromethane (DCM) (1:10, v/v), which afforded N,N’-diethyl-3,3’-bicarbazole 2a
in quantitative yields (>99%) at room temperature, in less than a minute (entry 1, Table 1).
Any anomaly from the above optimized conditions caused discouraging results. In brief,
absence of either oxidant or MSA did not afford the coupled product indicating the
importance/role of oxidant and acid in the above reaction (entries 2-3, Table 1, vide-infra).
Increasing or decreasing the amount of oxidant led to reduction in the product yield (entries
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-7, Table 1). Altering the oxidant (to PIFA or other quinone-based organic reagents, such as,
quinone (Q), 1,4-naphthoquinone (NQ), etc.) in place of DDQ/CA was not worthwhile
entries 8-9, Table 1). Other Brønsted acids attempted, instead of MSA, did not give fruitful
results (entry 10, Table 1). Also, changing the solvent gave depressed results (entry 11, Table
). Longer reaction duration affected the yield of bicarbazole negatively. One may notice
from Table 1 that the oxidative C–C coupling
(
1
a
Table 1. Optimization results with N-Ethylcarbazole 1a.
entry
Deviation from standard conditions
None
Time
1 min
6 h
Yield (%)
1
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>99
0
Without chloranil (or) DDQ
Without MSA
6 h
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DDQ (1.0 equiv)
1 min
1 min
1 min
1 min
12 h
87
79
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Chloranil (1.0 equiv.)
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DDQ (10 equiv.)
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Chloranil (10 equiv.)
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1.3 equiv. PIFA as oxidant in DCE
1,4-Quinone/1,4-Napthaquinone (2.0 equiv.)
AcOH instead of MSA
b
12 h
36 /0
1
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12 h
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b
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Toluene/Acetonitrile in place of DCM
10 min
60/83
a
All of the reactions were stirred at room temperature and vanishing of the starting material
b
c
was monitored by TLC. Starting material was isolated. Polar spots were found in TLC.
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reaction of N-ethylcarbazole 1a to offer 2a is efficient (near quantitative yields in less than a
minute) in presence of the organic oxidant DDQ/CA and MSA, which is more attractive than
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the earlier methods involving harsh conditions (see SI for comparison).
In principle,
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oxidative coupling of N-alkylcarbazole may occur at any of its active 1,3,6, and 8 positions.
Under the above reaction condition, only 3,3'-coupled product was obtained regioselectively,
and the oligomeric or polymeric side products through other active (1, 6 and 8) positions
were not observed at all. The isolated bicarbazole products were free from contaminants,
such as, excess quinones or hydroquinone after the reaction (see SI), facilitating easy
purification. Besides, the hydroquinone produced after the reaction can be recycled/reused
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after aerobic oxidation or treatment with conc. HNO to the corresponding DDQ or chloranil,
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as reported earlier.
The present methodology is indeed mild and efficient.
Having optimized the reaction conditions, the scalability of this reaction was examined. For
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this, one gram of 1a was subjected to DDQ/H conditions to provide 2a in quantitative yields,
within 1 min. After this successful attempt, we primarily tested the efficacy of the above
reaction with several N-alkylcarbazole derivatives (Eox ranging between ca. 1.09–1.35 V vs
1
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SCE, Scheme 2 and Table S1) decorated by various electron donating (ED) and
withdrawing (EW) substituents at 3-position; the other active positions 1, 6 and 8 were left
open. As expected, all the N-alkylcarbazoles (such as, R = hexyl, 1b; R = decyl, 1c; R =
benzyl, 1d) under the above optimized conditions underwent oxidative coupling to give 3,3'-
coupled products in good to excellent yields (79–99%, Scheme 2). In an analogous manner,
compounds 1e-g also conveniently afforded the corresponding 3,3'-bicarbazoles in very good
yields (92–98%). It is to be noted that the oxidative coupling did not occur at 1-position of
the carbazole ring containing ethyl/methoxy group. Similarly, biphenyl-substituted carbazole
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h when subjected to oxidative coupling conditions led to 71% of the bicarbazole 2h (10
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min.), which otherwise was obtained in 82% (15 min.) and 98% yields (15 min.) under
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chloranil/H (2.0 equiv. as well as 8.0 equiv., respectively) conditions. To our excitement,
carbazoles containing electron withdrawing substituents, such as, –Br (1i), –COOMe (1j) and
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–
COOH (1k) at 3-position were also conveniently converted to the corresponding
symmetrical 3,3'-bicarbazoles (2j-l) in good to excellent (84–99%) yields demonstrating
excellent functional group compatibility. To our surprise, compounds 1f,g,k did not offer the
corresponding bicarbazoles under CA conditions, and the unreacted starting material was
recovered quantitatively. This may probably be reasoned to the mild oxidizing ability of CA.
Fortunately, the compounds 2a (CCDC 1865706) and 2i (CCDC 1864769) were crystallized
and their structures were unequivocally confirmed by X-ray structural analysis.
Scheme 2. Oxidative coupling results of N-alkylcarbazoles.
2i
2a
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The oxidative C–C coupling was then investigated with various N-phenylcarbazoles (Scheme
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, Eox ranging between ca. 1.22–1.36 V vs SCE, Table S1). Principally, N-phenylcarbazole
possesses 3-open (para to N) positions and 4-open (ortho to N) positions active for oxidative
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coupling. When simple N-phenylcarbazole 3a (Eox = 1.24 V vs SCE) was subjected to the
optimized condition, only the symmetrical regioselective product, i.e., 3,3’-coupled product
of carbazole, was formed immediately in near quantitative yields (4a, 97%, Scheme 3); the
product 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) due to oxidative coupling at the N-phenyl
site or other/oligomeric side products from carbazole ring were not obtained at all. Similarly,
3
-substituted N-phenylcarbazole derivatives 3b-d underwent smooth oxidative coupling to
provide 3,3’-bicarbazoles (4b-d, 84–99%) in good to excellent yields. To our surprise,
carbazoles with substituents (irrespective of their nature) on the N-phenyl ring (3e-j)
proceeded very efficiently to yield the corresponding oxidative coupling products 4e-j. The
ortho-coupled products were not isolated.
Scheme 3. Oxidative coupling results of N-phenylcarbazoles.
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12a,g,13d
The observed results are encouraging and are superior to those reported earlier.
From
the above set of experiments, it is found that while the course of the reaction is unaltered, the
yields as well as the duration of oxidative coupling were notably affected by the nature of
substituents either at the carbazole nitrogen (as in 2a-d, 2f-g) or at the carbazole ring (as in
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g-i, 2j-k and 4a-d), and not mainly by substituents at the N-phenyl ring (as in 4e-j). This
may be ascribed to the effective conjugation (electronic effect) present within the ring (2e-k
and 4a-d) and the less effective conjugation experienced by the tilted (tilt angle deduced from
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X-ray is ca. 43-57) N-phenyl ring (4e-j, steric effect by ortho hydrogens). In general,
carbazoles containing ED group proceeded effectively when compared to carbazoles with
EW groups. The results of oxidative coupling in the case of N-alkylcarbazoles are better
when compared to N-phenylcarbazoles, which is probably due to the relatively high
1
6,19
ionization potentials of the latter.
It is important to mention that in all the above cases
coupling occurred only at 6-position (the open active position para to carbazole nitrogen)
12a,g,13d
regioselectively to offer 3,3'-bicarbazole as observed in the earlier cases.
The
preference to other possible 1,1'- and 1,3'-coupled products (via open positions ortho to
carbazole nitrogen) was not identified at this stage. This could probably be due to severe
steric effects at the reactive sites (i.e., 1-position) exerted by substituents at the carbazole
nitrogen. Advantageously, no oligomeric or polymeric carbazole side products were observed
under the tested reaction conditions, although there were active positions open and that the
16
bicarbazoles could further be oxidized easily (Eox = 0.8 V vs SCE). In all the above cases,
DDQ is found to be an efficient oxidant when compared to chloranil; especially, in cases 2h,
2
j, 4c-e and 4k, reaction with chloranil took longer duration and resulted in slightly lower
yields. This means that both chloranil and DDQ are suitable oxidants for carbazoles
containing electron donating groups, and for carbazoles with electron withdrawing groups,
DDQ turns out to be the best choice. Indeed, this method offers a high flexibility to
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
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4
4
4
5
5
5
5
5
5
5
5
5
5
6
synthesize 3,3'-bicarbazoles with various substituents directly in one-step without having to
introduce them at a later stage after coupling, which is actually very cumbersome and
8a
tedious.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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8
9
0
Further to understand the preferences for electronics and sterics in oxidative coupling, 2-
substituted (two open active positions; position 3 is sterically encumbered and position 6 is
steric-free) as well as 2,7-disubstituted carbazoles (5a-5d, both the positions 3 and 6 are
sterically conjested) were subjected to the optimized C–C coupling conditions (Scheme 4).
As expected, both 2-tert-butyl-N-ethylcarbazole (5a) and 2-chloro-N-ethylcarbazole (5b)
underwent oxidative coupling smoothly at the steric-free position-6 to provide 3,3'-
bicarbazoles 6a and 6b, respectively. It must be noted that oxidative coupling in these cases
occurs at the less hindered site (i.e., 6-position) of the carbazole though there is another open
site (3-position) situated adjacent to the 2-substituent. On the other hand, 2,7-
dibromocarbazole 5c successfully led to a sterically hindered 2,2',7,7'-tetrabromo-3,3'-
bicarbazole product 6c in moderate yields via the open active position. This means that if
both the active open positions (3- and 6-) contain a neighboring substituent each (at 2 and 7),
oxidative coupling happens through any of the free active position which once again may be
decided by the electronic effect of the substituent. Added to our excitement, when 2-
+
methoxy-N-ethylcarbazole 5d was treated with DDQ or CA/H , it provided the sterically
hindered bicarbazole 6d in excellent yields overcoming the steric barrier. It is noteworthy that
the C–C coupling occurred at the carbazole ring containing the electron-rich –OMe
substituent, as opposed to other cases (5a,b), supporting the strong contribution of electronic
(mesomeric) over steric effects.
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Scheme 4. Oxidative coupling results of 2,7-disubstituted N-ethylcarbazoles.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
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3
3
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3
3
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9
0
1
2
3
4
5
6
7
8
9
0
Interestingly, carbazoles containing strong electron withdrawing groups 7a-g (Scheme 5, Eox
19b
>
1.3 V vs SCE, Table S1) behaved differently. To our surprise, the 3-cyano (–CN)
substituted carbazole 7a offered a mixture of 3,3'-symmetrical (8'a, 48%) as well as 1,3'-
+
1
unsymmetrical bicarbazoles (8a, 52%) under DDQ/H conditions, as evidenced by the H
+
NMR spectrum. The same reaction did not offer any oxidative coupling product under CA/H
18
conditions probably due to its weak oxidizing ability (Ered = 0.02 V vs SCE). In contrast, 3-
cyano-N-phenyl-carbazole 7b afforded the oxidative 1,3'-unsymmetrical coupling product 8b
in 60% yield. Similarly, 3-nitrocarbazoles 7c-d yielded 1,3'-bicarbazoles 8c-d in 60-77%
yield, besides the corresponding 3,3'-bicarbazoles in 23-40% yield in just 1–5 minutes. In line
with this, carbazoles with other electron withdrawing functional groups, such as, formyl (–
CHO, 7e-g) and acetyl (–COCH3, 7h), at 3-position also provided 1,3'-bicarbazoles (8e-h)
almost exclusively (68–86%) under the oxidative coupling conditions; the other 3,3'-
bicarbazole was formed in 5–12% yield. These substrates required longer reaction time (12 h)
than usual, and in some cases (7b, 7g and 7h) unreacted starting material was also isolated.
2
Note that carbazoles substituted by strong electron withdrawing groups, –CH=C(CN) (7i)
furnished 1,3'-bicarbazole 8i in relatively lower yields. The low yield in the case of 7i → 8i is
probably due to the generation of polar polymeric product which may postulate a radical
intermediacy (vide infra) under the reaction conditions; N-vinylcarbazole is known to
22
undergo radical polymerization under oxidative (or electrochemical) conditions. Stirring the
1
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2
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4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 5. Oxidative coupling results of carbazoles containing EWD groups.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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2
3
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6
7
8
9
0
reaction in all the above cases for longer period (i.e., 12 h) did not improve/affect the yield of
the 1,3'-bicarbazoles 8 very much, suggesting the stability of the products under the reaction
conditions. Indeed, tuning the electronic nature of substituents at position-3 leads to 1,3'-
bicarbazoles over 3,3'-bicarbazoles is remarkable.
In all the above cases of carbazole, the ring containing withdrawing group is not involved in
oxidative coupling, probably due to the relatively electron deficient nature of the same
compared to the other ring of the carbazole unit. Moreover, the facile exclusive formation of
unsymmetrical 1,3'-bis(carbazoles) over 3,3'-bis(carbazoles) from a monosubstituted (EWG)
carbazole through oxidative coupling is remarkable. To the best of our knowledge, this type
of unsymmetrical oxidative coupling of carbazoles containing EW group to afford 1,3'-
carbazoles is not yet reported in the literature and is reported here for the first time. Most
importantly, DDQ is found to be very effective for carbazoles containing EW groups when
compared to chloranil. This may be understood very readily based on the differences in their
oxidation potentials and their ability to perform oxidation effectively (Ered 0.02 < 0.70 V vs
SCE).
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9
At this point, we questioned as to whether 1,1'-bicarbazole could be attained at all under the
oxidative coupling conditions, after blocking the active 3- and 6-positions of carbazole (Eox
=
1.38 – 1.64 V vs SCE, Scheme 6, Table S1). With this in mind, substrate 9a/9b (with two
open 1- and 8- positions ortho to N-) was subjected to the oxidative coupling reaction (DDQ
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
4
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5
6
0
1
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9
0
1
2
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0
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2
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7
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
or CA/H , Scheme 6). Unfortunately, no oxidatively coupled product was obtained even after
stirring the reaction for long duration (>12 h). This indicates that positions 3 and 6 are more
active than the 1 and 8 positions of carbazole as supported by the calculations reported
16,17
earlier.
To see if coupling can be enforced at the para position of the N-phenyl ring, both
the active 3- and 6-positions of N-phenylcarbazole were substituted or blocked as in 9c-d,
and they were subjected to oxidative coupling condition for prolonged (36 h) hours. This led
to no dimer formation (either at 1-/8-position or the para position of the N-phenyl ring) and
the unreacted starting material was isolated quantitatively (Scheme 6), which in turn
highlighted the steric effect offered by the N-alkyl/-phenyl ring at 1,8-positions and
abstention of nitrogen lone pair from conjugation with the tilted N-phenyl ring. Similarly, N-
acylcarbazole 9e (with open 1,3,6 and 8 positions, Eox = 1.64 V vs SCE) also did not afford
any oxidative coupling product, which could be reasoned due to the effective engagement of
nitrogen lone pair in resonance with the N-acyl unit rather than with the rings. This once
again emphasized the role of nitrogen lone pair and its availability on the carbazole nitrogen
in effecting oxidative coupling reactions successfully (for example, Eox of TPA < Eox of N-
phenylcarbazole). The above results clue that the oxidative coupling is very mild and
selective under the tested conditions.
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2
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4
4
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4
4
4
4
4
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5
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5
5
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5
5
5
5
5
6
Scheme 6. Oxidative coupling results of 3,6-disubstituted carbazoles.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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5
6
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8
9
0
To validate if this method can be further extended to 9H-carbazole and to understand the
steric influence/contribution of substituents at the 9-position of carbazole towards 1,1'- or
1
,3'-dimers, a set of 9H-carbazoles containing substituents at 3, 3 and 6, 2, and 2 and 7
positions were examined under the oxidative coupling conditions (Scheme 7). The simple
19
9
H-carbazole 10a (Eox = 1.16 V vs SCE) when subjected to oxidative coupling yielded 3,3’-
+
+
bicarbazole 11a in 93% under DDQ/H , and in 83% under chloranil/H conditions. Similarly,
3-ethylcarbazole 10b also afforded the bicarbazole 11b (83–94%) selectively without
formation of other products, as observed in earlier cases. When both the active positions of
carbazole are blocked and the ortho positions are free from sterics as in 3,6-
dibromosubstituted 9H-carbazole 10c, the oxidative coupling yielded 1,1'-bicarbazole 11c in
low yield (36%) emphasizing the role of sterics (due to substituents) at carbazole nitrogen
restricting 1,1'-bicarbazole formation in 9a-c. The 2-substituted or 2,7-disubstituted 9H-
carbazoles 10d-f also provided 3,3’-bicarbazoles (11d-f) in good to moderate yields.
Noticeably, the sterically-free 6-position underwent oxidative coupling preferably over 1, 3
or 8 positions as seen with 10e-f. It is important to state that the sterically hindered product
1
1f is also accessible from 10f in appreciable yields. That is, when two active positions (3-
and 6-) are open with a substituent at its neighboring position, say at 2 (as in 10d, 5c), the
oxidative coupling occurs at the sterically-free site, that is at 6 (as in 11d, 6c), which once
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again proposes electronics play a crucial role overcoming sterics in oxidative coupling
reactions.
Scheme 7. Oxidative coupling results of 9H-carbazoles.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
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3
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0
1
2
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0
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2
3
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0
1
2
3
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8
9
0
From all of the above experiments one may carefully notice that the reactivity trend mostly
follows the Eox of the precursor carbazoles. It is inferred that higher the oxidation potential
(Eox > 1.6 V vs SCE), greater is the difficulty to effect oxidation. Moreover, the nature and
stability of the intermediates also play crucial roles in the course of oxidative coupling. In
early days, various oxidation pathways of carbazole were proposed and studied by
electrochemical means. These studies suggested the involvement of an electrochemically
16,19
generated carbazole cation radical (Cz•+) before coupling to bicarbazoles (BCzs).
Well
known is the fact that several electron-rich aromatic compounds, including carbazoles, form
2
3
charge-transfer complexes with various electron-deficient compounds such as DDQ/CA. To
garner insights into the mechanism of oxidative C–C coupling of carbazoles mediated by
+
DDQ or CA/H , the reaction course was monitored initially by UV-vis-NIR absorption
spectroscopy. As expected, a 1:1 mixture of solutions of N-ethylcarbazole (1a, λmax = 332,
3
47 nm) and DDQ (λmax = 353, 387 nm) in DCM (in the absence of acid) turned blue
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5
5
6
corresponding to the absorption at a λmax value of 647 nm in the visible region (see Figure 1),
which may be attributed to a charge-transfer (CT) complex formed between the electron
2
3
donor carbazole and acceptor DDQ. The addition of weak acids, such as AcOH, did not
affect the CT complex (1a–DDQ) and the CT band (shape and position) very much. In
contrast, step-wise addition of MSA to the blue-colored solution, immediately resulted in the
evolution of two new bands at ca. 638 and 1117 nm. This near-IR band resembled the
0
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4
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6
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8
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2
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7
8
9
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9
0
+
absorption spectrum recorded after the treatment of BCz 2a with either DDQ/H or one-
electron oxidant TPA-salt (tris(4-bromophenyl)ammoniumyl hexachloroantimonate salt).
Based on the experiments with bicarbazole 2a and based on the previous literature
13d,16
evidences,
one may attribute this new set of main bands to the radical cation of the 3,3'-
bicarbazole (2a•+) and not to the inter-valence charge-transfer band of distonic cation radical
after oxidative coupling. This supports the role of MSA in promoting electron-transfer (donor
→ acceptor) during oxidative coupling of carbazole. Treatment of Cz with MSA alone did
not result in the formation of bicarbazole, which indicates the absence of arenium cation
1
8c,d
mechanism.
To add to this, the treatment of 1a with TPA-salt also resulted a minor
absorption band corresponding to 1a•+ notably at ca. 735 nm, which rapidly diminished in
intensity and grew as a new band at 1170 nm with time (see SI). It appears that the oxidative
coupling of carbazole via 1a•+ proceeds very rapidly as soon as the CT complex was treated
with acids, such as, MSA. At this point, it is important to recall that the bimolecular rate
8
constant for the electrochemical oxidative coupling of carbazoles is calculated to be ca. 10 –
6
-1 -1 16
1
0 mol s , which is far higher (three to five orders of magnitude) than that of
triphenylamines, supports our observation. Consequently, we could not capture the radical
cation of N-ethylcarbazole (1a•+) generated under oxidative conditions by UV-vis absorption
spectroscopic means. Hence, 3,6-di-tert-butyl-N-ethylcarbazole (9b), where the active
positions are blocked and the generated radical cation would be trapped within the carbazole
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rings without further possibiliy for oxidative coupling, was chosen for our study. As observed
earlier, a 1:1 mixture of 9b and DDQ formed a charge-transfer complex (9b–DDQ, λmax abs =
678 nm) which upon addition of MSA finally resulted new absorption bands at around 725 as
1
3d,16
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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0
1
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0
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2
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0
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0
1
2
3
4
5
6
7
8
9
0
well as 815 nm,
which was very different from that of the bicarbazole radical cation
(
2a•+) and also resembled the absorption spectrum obtained by the treatment of 9b/1a with
TPA-salt (λmax = 728, 816 nm) pointing to the formation/involvement of the carbazole radical
cation (9b•+/1a•+) intermediate during the oxidative coupling of carbazoles. This result is in
line with the earlier studies and further highlights the stability of radical cations of 3,6-
disubstituted carbazoles (for example, 9b) as well as the 3,3'-bicarbazole (for example, 2a)
under the reaction conditions. Also, an EPR spectrum recorded for 9b under the reaction
condition revealed a stable strong broad signal with no hyperfine structure and a g value of
2.1646 resembling that of the one with TPA-salt (g = 2.1649). This explains the intermediacy
of 1a•+ in the oxidative coupling reactions.
With the above information that suggests the presence of Cz•+ during oxidative coupling and
also in analogy with the previous reports, a step-wise mechanism has been proposed for the
+
formation of BCz from Cz under DDQ or CA/H conditions (Scheme 8). As may be seen, the
formation of the charge-transfer complex (Cz-DDQ) between carbazole and DDQ is the first
step. Next, the addition of strong acid promotes rapid electron transfer from electron-rich
carbazole to the electron-deficient protonated DDQ (more electrophilic). The Cz•+ thus
2+
formed dimerizes immediately to form a dication (BCzH
2
) which further loses two protons
immediately to produce bicarbazole BCz in the last step. Now,
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1
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2
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2
2
2
2
2
2
2
2
3
3
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3
3
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3
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3
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6
3
2
1
0
1
a + DDQ
3
2
1
0
9b + DDQ
+
+
1a + DDQ/H
.
+
9b + DDQ/H
9b + TPA-salt
9b
.
+
1a + TPA-salt
2a
+
2a + DDQ/H
1
a-DDQ
CT complex
0
1
2
3
4
5
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7
8
9
0
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2
3
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8
9
0
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8
9
0
1
2
3
4
5
6
7
8
9
0
.
+
1a
9b-DDQ CT complex
400 800 1200 1600 2000
400 800 1200 1600 2000
Wavelength, nm
Wavelength, nm
+
1
600
9b + DDQ/H
b + TPA salt
9
800
0
-800
-
1600
333
336
339
342
Field, mT
Figure 1. (Left) UV-vis-NIR absorption spectroscopy studies of 1a→2a for tracing carbazole
radical cation (1a•+) intermediate. (Right) UV-vis-NIR absorption spectrum of 9b•+ species
+
under the optimized conditions. (Bottom) EPR spectrum of 9b upon treatment with DDQ/H
as well as TPA-salt showing the presence of radical cation (9b•+) mediacy in the oxidative
coupling reactions. Photographs reveal the color of the intermediates generated during the
reaction.
simple comparison of the redox potentials of the monomer Cz (Eox = 1.16 V vs SCE) and
24
bicarbazole BCz (Eox = 0.80, 1.1 V vs SCE) dictates that the latter is a better electron donor
than the former, and hence BCz must further undergo oxidation by donating an electron
either to Cz or to DDQ under the reaction conditions and generate BCz•+, which ultimately
2
5
is neutralized under the regular work-up conditions (using aqueous bases, TEA, etc). Thus,
excess amounts of oxidant in the reaction medium may lead to higher oligomers or polymers
rapidly (as seen in Table 1). A similar mechanism involving Cz•+ was proposed when metal-
12a,g
based oxidants were used for the oxidative coupling reactions.
The other possible
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coupling pathways postulated in the literature are: (i) aromatic electrophilic substitution-type
reaction of Cz•+ with neutral Cz leading to
Scheme 8. Mechanistic proposal for the oxidative coupling of carbazoles.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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7
8
9
0
distonic cation radical and subsequent loss of an electron and two protons leading to
aromatization, (ii) initial hydride ion abstraction from Cz by DDQ followed by an aromatic
electrophilic substitution-type reaction of Cz+ with neutral Cz and loss of proton and
aromatization, and (iii) protonation (weak) of carbazole to provide the quaternary ammonium
salt, and then loss of a hydrogen atom to give the carbazolyl cation radical that initiates
coupling. Among the possible reaction mechanisms, the one involving radical cation
dimerization proposed herein and the electrophilic substitution-type reaction by the radical
cation are meaningful insofar as the high reactivity of carbazoles is concerned. But, on candid
comparison of the bimolecular rate constant values of oxidative coupling for a set of
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carbazoles, it makes more sense to believe that the oxidative coupling of carbazoles proceeds
via a radical cation dimerization followed by deprotonation pathway.
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Conclusions
In summary, we have developed an efficient methodology (metal-free, mild, simple,
economic) for the oxidative coupling of carbazoles using recyclable organic oxidants (DDQ
or CA/MSA). It is found that the oxidative coupling of electron-rich carbazoles proceeded
very readily when compared to their electron-deficient analogs. Interestingly, the introduction
2 3
of strong electron withdrawing groups, such as,–NO , –CN, –COCH and –CHO at 3-position
of carbazole led to 1,3'-carbazole dimers in a regioselective manner. Such a substituent-based
selectivity/reactivity profile in the regioisomeric discrimination of the oxidative dimerization
of carbazoles is heretofore unreported. The proposed conditions offer excellent functional
group tolerance, and even sterically hindered carbazoles underwent oxidative coupling
smoothly to provide dimers in very good yields. By means of UV-vis-NIR absorption and
EPR spectroscopy, it is shown that the mechanism of oxidative dimerization of carbazoles
involves the intermediacy of carbazole cation radical (Cz•+). Presently, our research efforts
are towards the development of novel transformations using this reagent system, and
development of interesting carbazole dimers of biological importance.
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EXPERIMENTAL SECTION
General Aspects. All reagents were used as purchased. Solvents, such as, dichloromethane
(DCM), dimethyl sulphoxide (DMSO), acetonitrile (ACN) and 1,2-dichloroethane (DCE)
1
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were dried and distilled over CaH
2
, toluene was distilled over sodium. All reactions were
gas atmosphere and were monitored by TLC
carried out in oven-dried glassware under N
2
analysis using Merck silica gel (60 F254) pre-coated plates (0.25 mm). The compounds were
visualized under a UV lamp (366 or 254 nm) in UV chamber or using phosphomolybdic acid
(PMA) or 2,4-dinitrophenyl hydrazine (2,4-DNP) solutions as stains to indicate the
compound as a spot to the nacked-eye. The crude product was purified by silica gel (100-200
mesh or 60-120 mesh) column chromatography. Melting points reported are corrected. The
infrared spectra of compounds were recorded on a JASCO FT/IR-4100 spectrometer using
-1
1
dry KBr pellet and IR signals are quoted in wavenumbers (cm ). H (400 or 500 MHz) and
1
3
C (100 or 125 MHz) NMR spectra were recorded at ambient temperature using a Bruker
Avance FT-NMR (400 or 500 MHz) spectrometer in deuterated chloroform (CDCl ) or
dimethylsulfoxide (DMSO-d ) with TMS as the internal reference. All chemical shift values
are reported in parts per million (ppm, δ). While H NMR spectra are referenced to the
3
6
1
3 6
residual proton solvent peak (CDCl , δ = 7.26 ppm; DMSO-d , δ = 2.50 ppm) or calibrated to
13
3
tetramethylsilane (δ = 0.00), C NMR spectra are referenced to CDCl , δ = 77.16 ppm or
1
DMSO-d
6
, δ = 39.51 ppm, respectively. The H NMR multiplicities are abbreviated as
follows: s, singlet; d, doublet; t, triplet; q, quartet; qt, quintet; m, multiplet; dd, doublet of
doublet; td, triplet of doublet; dt, doublet of triplet; tt, triplet of triplet; bs, broad singlet, and
their coupling constants (J) are reported in hertz (Hz). High-resolution mass spectra (HRMS)
were recorded on a Q-Tof Micro micromass spectrometer. UV-vis absorption spectra for
simple starting materials were recorded on a AGILENT 8453 diode-array spectrophotometer
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and UV-vis-NIR absorption spectra were recorded on a Shimadzu UV-3100 UV-vis-NIR
absorption spectrophotometer using commercially purchased spectroscopic grade solvents.
The starting materials, such as 3-bromo-9-(p-tolyl)-9H-carbazole (3e), carbazole (10a), 3-
ethyl-9H-carbazole (10b), 2-chloro-9H-carbazole (10e) and 2,7-dibromo-9H-carbazole (10f)
were commercially purchased and were used as received. Other carbazoles, such as, N-ethyl
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27
28
carbazole (1a), 9-hexyl-9H-carbazole (1b), 9-decyl-9H-carbazole (1c), 9-benzyl-9H-
2
9
30
carbazole (1d), 9-ethyl-3-methoxy-9H-carbazole (1g), 3-bromo-9-hexyl-9H-carbazole
31
32
(
1j), methyl 9-ethyl-9H-carbazole-3-carboxylate (1k), 9-ethyl-9H-carbazole-3-carboxylic
33
34
35
acid (1l), 9-phenyl carbazole (3a), 3,9-diphenyl-9H-carbazole (3b), 3-bromo-9-phenyl-
3
6
37
9
H-carbazole (3d), 9-(p-tolyl)-9H-carbazole (3f), 9-(1,1’-biphenyl-4-yl)-9H-carbazole
38
39
40
(
3g), 9-(4-fluorophenyl)-9H-carbazole (3h), 9-(4-bromophenyl)-9H-carbazole (3j), 9-(p-
4
1
42
acetylphenyl)-9H-Carbazole (3k), N-ethyl-2,7-dibromocarbazole (5c), 2-ethoxy-9-ethyl-
4
3
44
9H-carbazo le (5d), 9-hexyl-9H-carbazole-3-carbonitrile (7a), 9-phenyl-9H-carbazole-3-
45
46
46
carbonitrile (7b), 9-ethyl-3-nitro-9H-carbazole (7c), 3-nitro-9-phenyl-9H-carbazole (7d),
4
7
48
9
-ethyl-3-formyl-9H-carbazole (7e), 9-hexyl-3-formyl-9H-carbazole (7f), 9-phenyl-9H-
45
49
carbazole-3-carbaldehyde (7g),
3-acetyl-9-hexyl-9H-carbazole (7h),
9-ethyl-3-
50
51
(
dicyanovinyl)-9H-carbazole (7i), 3,6-dibromo-9-hexyl-9H-carbazole (9a), 3,6-di-tert-
5
2
53
butyl-9-ethyl-9H-carbazole (9b), 3,6-dibromo-9-phenyl-9H-carbazole (9c), 3-(biphenyl-2-
5
4
55
yl)-6-bromo-9-phenyl-9H-carbazole (9d), 9-acetyl-9H-carbazole (9e), 3,6-dibromo-9H-
5
6
57
carbazole (10c), 2-(tert-butyl)-9H-carbazole (10d) were synthesized according to the
1
13
literature reported procedures, characterized by H and C NMR spectroscopy and the data
26-57
were verified with the cited literature reports.
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Synthesis of 3,3’- and 1,3’-bicarbazoles via the oxidative C–C coupling method. A
general procedure for the synthesis of 3,3’- and 1,3’-bicarbazoles from the corresponding
carbazole precursors is described below.
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General procedure for the oxidative coupling of carbazoles. A solution of the carbazole
derivative (0.8 mmol, 1.0 equiv.) in dry DCM (10.0 mL) was cooled to 0 °C, and
methanesulphonic acid (MSA) was added slowly at this temperature. After stirring the
contents for few minutes at 0 °C, DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone, 370 mg,
1
.6 mmol, 2.0 equiv.) or chloranil (401 mg, 1.6 mmol, 2.0 equiv.) was added. Immediately,
the color of the reaction mixture turned blue-green to blue depending on the substrate. The
progress of the reaction was monitored by TLC (thin layer chromatography) regularly. As
soon as the starting material disappeared completely, as noticed by TLC, the saturated
3
NaHCO solution was carefully added under ice-cold conditions. The whole of the reaction
contents was transferred into a separating funnel and the organic portion was extracted into
chloroform (3 × 10 mL). The combined organic layer was washed once again with saturated
sodium bicarbonate solution (in case of DDQ as the oxidant) or 2N NaOH (in case of
chloranil as the oxidant). Now, the aqueous portion appeared orange to red in color and the
organic portion remained colorless. The organic layer was then washed with brine (saturated
2 4
sodium chloride) solution, dried over anhydrous Na SO , filtered and dried under vacuum.
The crude residue was purified by silica-gel column chromatography using hexane-ethyl
acetate mixtures as the eluent. The pure products isolated were colorless, pale yellow to dark
brown solids or liquids.
A typical procedure for the synthesis of N,N'-diethyl-3,3'-bicarbazole, starting from N-ethyl
carbazole is given below.
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Typical procedure for the synthesis of N,N-diethylbicarbazole (2a) from N-ethyl
2
4
carbazole (1a). To a solution of N-ethyl carbazole (159 mg, 0.81 mmol, 1.0 equiv.) in dry
dichloromethane (10.0 mL) at 0 °C methanesulphonic acid (1.0 mL) was introduced. After
stirring the contents for a period of 2 3 minutes at this temperature, DDQ (370 mg, 1.63
mmol, 2.0 equiv.) was added. Immediately, the reaction mixture turned into deep-blue colour.
The reaction mixture stirred further and allowed to reach room temperature slowly. The
advancement of the reaction was noted carefully by TLC. As soon as the reaction was
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complete (1 min, as noticed on TLC), saturated NaHCO solution was added carefully into
the flask under ice-cold conditions. The organic portions were extracted into chloroform (3 ×
10 mL) as the colorless layer. The combined organic layer was repeatedly washed with
saturated NaHCO
3
solution to remove 2,3-dichloro-5,6-dicyanobenzoquinone completely,
SO , filtered, concentrated and
followed by washing with brine, dried over anhydrous Na
2
4
dried. The crude product obtained was subjected to silica-gel column chromatography using
hexane-ethyl acetate mixtures (5% ethyl acetate in hexane) as the eluent. The pure product
(
off-white solid) was obtained in quantitative yield (157 mg, 0.81 mmol, >99%).
Time: 1 min (DDQ/chloranil). Yield: 157 mg, >99% (Chloranil); 157 mg, >99% (DDQ). Off-
24
-1
white solid. R
f
= 0.4 (19:1, hexane/EtOAc). Mp: 191-192 ˚C (lit. 189 ˚C). IR (KBr, cm ):
1
3
049, 2973, 2927, 1599, 1470, 1379. H NMR (400 MHz, CDCl
3
): δ 8.41 (d, J = 1.28 Hz,
2H), 8.19 (d, J = 7.72 Hz, 2H), 7.83 (dd, J = 8.44 and 1.68 Hz, 2H), 7.49 (d, J = 8.48 Hz,
H), 7.48 (dt, J = 8.0 and 1.20 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.25 (dt, J = 8.0 and 1.20
2
13
1
Hz, 2H), 4.41 (q, J = 7.2 Hz, 4H), 1.47 (t, J = 7.2 Hz, 6H). C{ H} NMR (100 MHz,
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CDCl
3
): δ 140.5, 139.1, 133.5, 125.8, 125.7, 123.6, 123.3, 120.6, 119.1, 118.9, 108.8, 108.7,
+
3
7.7, 14.0. HRMS (ESI-TOF) m/z: [M + H] Calcd. for C28
H
25
N
2
, 389.2018; found,
389.2025.
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58
9
,9'-Dihexyl-9H,9'H-3,3'-bicarbazole (2b)
Time: 1 min (DDQ/chloranil). Yield: 161 mg, 79% (DDQ); 186 mg, 91% (chloranil). Pale
-1
yellow gummy liquid. R
f
= 0.3 (19:1, hexane/EtOAc). IR (neat, cm ): 3051, 2952, 2926,
1
1
465, 1378, 1238. H NMR (400 MHz, CDCl
3
): δ 8.41 (d, J = 1.32 Hz, 2H), 8.19 (d, J = 7.68
Hz, 2H), 7.83 (dd, J = 8.44 and 1.68 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.48 (dt, J = 8.40 and
1.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.25 (dt, J = 8.0 and 1.0 Hz, 2H), 4.35 (t, J = 7.24 Hz,
13
1
4
H), 1.91 (q, J = 7.24 Hz, 4H), 1.47-1.23 (m, 12H), 0.88 (t, J = 7.2 Hz, 6H). C{ H} NMR
(
100 MHz, CDCl
3
): δ 141.1, 139.7, 133.5, 125.8, 125.7, 123.6, 123.2, 120.6, 119.1, 118.9,
+
1
09.0, 108.9, 43.4, 31.8, 29.2, 27.2, 22.7, 14.2. HRMS (ESI-TOF) m/z: [M + H] Calcd. for
36 41 2
C H N , 501.3270; found, 501.3291.
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,9'-Didecyl-9H,9'H-3,3'-bicarbazole (2c)
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Time: 1 min (DDQ/chloranil). Yield: 197 mg, 79% (DDQ); 205 mg, 82% (chloranil). Pale
-1
brown gummy liquid. R
f
= 0.2 in hexane. IR (KBr, cm ): 3054, 3018, 2922, 1623, 1593,
1
1
492, 1452, 1362, 1324, 1278, 1258, 1229, 1176, 1164, 1068, 1011. H NMR (400 MHz,
3
CDCl ): δ 8.40 (d, J = 1.44 Hz, 2H), 8.18 (d, J = 7.64 Hz, 2H), 7.83 (dd, J = 8.48 and 1.8 Hz,
2
H), 7.49 (d, J = 8.52 Hz, 2H), 7.48 (dt, J = 8.16 and 1.08 Hz, 2H), 7.43 (d, J = 8.04 Hz, 2H),
.24 (dt, J = 8.0 and 1.2 Hz, 2H), 4.34 (t, J = 7.2 Hz, 4H), 1.92 (qt, J = 7.2 Hz, 4H), 1.47-1.22
7
1
3
1
(m, 28H), 0.87 (t, J = 6.8 Hz, 6H). C{ H} NMR (100 MHz, CDCl
3
): δ 141.1, 139.7, 133.6,
1
2
25.8, 125.7, 123.6, 123.2, 120.6, 119.1, 118.9, 109.0, 108.9, 43.4, 32.0, 29.69, 29.67, 29.6,
+
56 2
9.4, 29.2, 27.5, 22.8, 14.2. HRMS (ESI-TOF) m/z: [M] Calcd. for C44H N , 612.4443;
found, 612.4427.
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,9'-Dibenzyl-9H,9'H-3,3'-bicarbazole (2d)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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Time: 1 min (DDQ/chloranil). Yield: 207 mg, > 99% (DDQ); 207 mg, > 99% (chloranil).
-
1
Amorphous white solid. R
f
= 0.3 (19:1, hexane/EtOAc). Mp: 238-240 °C. IR (KBr, cm ):
3
051, 3028, 3008, 2923, 1627, 1602, 1485, 1456, 1376, 1330, 1258, 1212, 1154, 1064, 1027.
1
H NMR (500 MHz, CDCl
3
): δ 8.41 (d, J = 1.7 Hz, 2H), 8.19 (dd, J = 7.65 and 0.5 Hz, 2H),
7.76 (dd, J = 8.4 and 1.4 Hz, 2H), 7.43 (t, J = 8.3 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.37 (d, J
13
1
=
8.0 Hz, 2H), 7.29-7.21 (m, 8H), 7.17 (d, J = 8.0 Hz, 4H), 5.52 (s, 4H). C{ H} NMR (100
MHz, CDCl
3
): δ 141.3, 140.0, 137.4, 133.9, 128.9, 127.6, 126.6, 126.1, 125.9, 123.8, 123.4,
+
120.6, 119.4, 119.1, 109.3, 109.2, 46.9. HRMS (ESI-TOF) m/z: [M] Calcd. for C38
H
28
N
2
,
5
12.2252; found, 512.2256.
6
,6',9,9'-Tetraethyl-9H,9'H-3,3'-bicarbazole (2e)
Time: 1 min (DDQ/chloranil). Yield: 44 mg, 98% (DDQ); 44 mg, 98% (chloranil). Dull
-1
white solid. R
f
= 0.35 (19:1, hexane/EtOAc). Mp: 216-217 °C. IR (KBr, cm ): 3009, 2961,
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1
2
926, 2853, 1735, 1483, 1451, 1380, 1346, 1309, 1231, 1216, 1151. H NMR (400 MHz,
CDCl ): δ 8.41 (s, 2H), 8.03 (s. 2H), 7.82 (dd, J = 8.4 and 1.6 Hz, 2H), 7.47 (d, J = 8.4 Hz,
2H), 7.38-7.31 (m, 4H), 4.40 (q, J = 7.2 Hz, 4H), 2.87 (q, J = 7.6 Hz, 4H), 1.47 (t, J = 7.2 Hz,
3
1
3
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
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6
7
8
9
0
1
2
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8
9
0
1
2
3
4
5
6
7
8
9
0
6
1
3
H), 1.37 (t, J = 7.6 Hz, 6H). C{ H} NMR (100 MHz, CDCl ): δ 139.4, 139.1, 135.0,
33.4, 126.1, 125.5, 123.6, 123.5, 119.4, 119.1, 108.7, 108.5, 37.8, 29.9, 16.7, 14.0. HRMS
+
(ESI-TOF) m/z: [M] Calcd. for C32
H
32
N
2
, 444.2565; found, 444.2554.
59
9,9'-Diethyl-6,6'-dimethoxy-9H,9'H-3,3'-bicarbazole (2f)
f
Time: 1 min (DDQ). Yield: 28 mg, 61% (DDQ). Dull white solid. R = 0.39 (9:1,
-
1
hexane/EtOAc). Mp: 101-102 °C. IR (KBr, cm ): 2967, 2920, 2852, 1740, 1725, 1632, 1595,
1
1569, 1485, 1448, 1329, 1277, 1214, 1199, 1173, 1151, 1089, 1032. H NMR (400 MHz,
CDCl
3
): δ 8.36 (s, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 1.68 Hz, 2H), 7.47 (d, J = 8.44
Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.14 (dd, J = 8.56 and 1.84 Hz, 2H), 4.39 (q, J = 7.2 Hz,
13
1
4H), 3.96 (s, 6H), 1.46 (t, J = 7.2 Hz, 6H). C{ H} NMR (100 MHz, CDCl
3
): δ 153.8, 139.7,
1
35.7, 133.2, 125.7, 123.6, 123.5, 119.1, 115.1, 109.4, 108.9, 103.7, 56.4, 37.9, 14.1. The
above reaction was not successful with chloranil and the starting material was recovered
quantitatively.
2
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The Journal of Organic Chemistry
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,9'-Dihexyl-6,6'-dimethoxy-9H,9'H-3,3'-bicarbazole (2g)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
3
3
3
3
3
3
4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
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7
8
9
0
1
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0
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9
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3
4
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7
8
9
0
f
Time: 1 min (DDQ). Yield: 43 mg, 94% (DDQ). Pale yellow gummy liquid. R = 0.5 (19:1,
-1
hexane/EtOAc). IR (KBr, cm ): 2953, 2923, 1736, 1631, 1579, 1486, 1459, 1325, 1289,
1
1253, 1215, 1166, 1096, 1032. H NMR (400 MHz, CDCl
3
): δ 8.37 (s, 2H), 7.80 (d, J = 8.08
Hz, 2H), 7.69 (s, 2H), 7.46 (d, J = 8.44 Hz, 2H), 7.33 (d, J = 8.72 Hz, 2H), 7.13 (dd, J = 8.6
Hz and 1.36 Hz, 2H), 4.31 (t, J = 7.2 Hz, 4H), 3.97 (s, 6H), 1.89 (qt, J = 7.2 Hz, 4H), 1.45-
13
1
1.24 (m, 12H), 0.88 (t, J = 6.8 Hz, 6H). C{ H} NMR (100 MHz, CDCl
3
): δ 153.6, 140.2,
1
2
5
36.1, 133.0, 125.6, 123.5, 123.3, 118.9, 115.0, 109.6, 109.1, 103.5, 56.3, 43.5, 31.8, 29.2,
+
7.2, 22.7, 14.2. HRMS (ESI-TOF) m/z: [M] Calcd. for C38
44 2 2
H N O , 560.3403; found,
60.3372. The above reaction was unsuccessful with chloranil and the starting material was
recovered quantitatively.
6
,6'-Bis([1,1'-biphenyl]-2-yl)-9,9'-dihexyl-9H,9'H-3,3'-bicarbazole (2h)
N
N
2
9
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