A straight access to functionalized carbazoles by tandem reaction between indole and nitrobutadienes

Article abstract of DOI:10.1016/j.tet.2015.05.046

Abstract As a continuation of our research on the synthetic exploitation of the nitrobutadienic building-blocks obtained from the ring-opening of nitrothiophenes, we herein report about their reaction with the π-nucleophilic indole. Thanks to their double Michael-acceptor nature, 2,3-dinitro and 2-nitro-3-phenylsulfonyl substituted 1,3-butadienes produce poly-functionalized carbazoles through a double (inter-+intra-molecular) conjugate addition, followed by aromatization of the newly built ring. Significance is attached to the results obtained in fluorinated solvents such as trifluoroethanol, whereby a mild process, with no need for catalysis, overcomes some practical difficulties otherwise limiting the scope of the reaction. Besides the mechanistic aspects, the reaction encompasses motifs for a synthetic interest, mainly in the field of further-tunable arylcarbazoles endowed with predictable applicative properties, e.g., as fluorescent devices.

Full text of DOI:10.1016/j.tet.2015.05.046

Tetrahedron 71 (2015) 7421e7435
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A straight access to functionalized carbazoles by tandem reaction
between indole and nitrobutadienes
Lara Bianchi, Massimo Maccagno, Marcella Pani, Giovanni Petrillo, Carlo Scapolla,
*
Cinzia Tavani
ꢀ
Dipartimento di Chimica e Chimica Industriale, Universita di Genova, Via Dodecaneso 31, I-16146 Genova, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
As a continuation of our research on the synthetic exploitation of the nitrobutadienic building-blocks
obtained from the ring-opening of nitrothiophenes, we herein report about their reaction with the
Received 30 January 2015
Received in revised form 5 May 2015
Accepted 13 May 2015
p
-nucleophilic indole. Thanks to their double Michael-acceptor nature, 2,3-dinitro and 2-nitro-3-
phenylsulfonyl substituted 1,3-butadienes produce poly-functionalized carbazoles through a double
(inter-þintra-molecular) conjugate addition, followed by aromatization of the newly built ring. Signifi-
cance is attached to the results obtained in fluorinated solvents such as trifluoroethanol, whereby a mild
process, with no need for catalysis, overcomes some practical difficulties otherwise limiting the scope of
the reaction. Besides the mechanistic aspects, the reaction encompasses motifs for a synthetic interest,
mainly in the field of further-tunable arylcarbazoles endowed with predictable applicative properties,
e.g., as fluorescent devices.
Available online 20 May 2015
Keywords:
Nitrogen heterocycles
Michael additions
Perfluorinated solvents
Carbazoles
Ó 2015 Elsevier Ltd. All rights reserved.
Nitrobutadienes
1. Introduction
reactions,4 the corresponding sulfones 2 and 4 (Y¼Z¼H) undergo
the expected indole addition to the nitrovinyl moiety, respectively
In spite of aromaticity, adequately functionalized thiophenes
can be effectively opened following the nucleophilic attack by
a secondary amine,1 providing a valuable access to synthetically
useful, versatile, nitrobutadienic building-blocks (Scheme 1), some
of which endowed with biological activity.2 From these, during the
years, we have obtained a wide collection of heterocyclic targets
within metal-free overall ring-opening/ring-closing procedures
characterized by a high atom economy.3 Such targets encompass
e.g., pyrroles, pyrazoles, isoxazoles and pyrazines, to cite only
N-heterocycles, whose occurrence in biologically active molecules
of both natural and synthetic origin is well-known and fosters
continuing efforts in search for original preparative protocols.
Among more recent research lines in this particular field, we
have investigated the behavior of some of our electrophilic
producing the indole derivatives 6 and 7, the latter as the result of
a 1,4-Michael addition on the butadienic moiety (Scheme 2). More
interestingly, when dinitrobutadienes 5 are reacted in the same
conditions, 1,3,4- and 1,2,4-substituted carbazoles (Scheme 2, 8 and
9, respectively) are isolated as the main products,3d together with
minor amounts of the tetrasubstituted derivative 10, as the final
result of a double Michael addition.
The carbazole nucleus is a key structural motif present in a va-
riety of biologically important compounds either of natural or of
synthetic origin5 endowed with e.g., antimalarial, antitumor, anti-
plasmodial, and antitrypanosomal activities. Besides, carbazoles
have recently assumed growing importance also in the field of
materials science,6 due to their photorefractive, photoconductive,
hole-transporting and light-emitting properties. Accordingly, the
synthesis of carbazoles,7,8 including naturally occurring ones, has
received considerable attention and the development of green and
efficient approaches to such core structure with different functional
groups is a major objective in organic synthesis currently, as tes-
tified by the impressive number of publications in the field.
In consideration of the interest of the subject, it seemed
worthwhile to explore more deeply the behavior of derivatives 5, in
order to better define the scope of the process and to improve its
efficiency.
building-blocks with the p-nucleophilic indole. Preliminary results
have shown an intriguing variability in their reactivity, depending
on the character, the number and the position of substituents on
the nitrobutadienic fragment.3d
In particular, we reported that while model sulfides 1 and 3
(Scheme 1, Y¼Z¼H) react too sluggishly in Zn(OAc)2-catalyzed
* Corresponding author. E-mail address: cinzia.tavani@unige.it (C. Tavani).
http://dx.doi.org/10.1016/j.tet.2015.05.046
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
Scheme 1. Ring-opening derivatives of nitrothiophenes.
Scheme 2. Preliminary results from our previous work on the subject.3d
2. Results and discussion
substituent on the aryl moiety (f, g). Yields too are influenced by
steric effects, as evident for b versus c and versus d; h versus i; j
versus k. In the case of the particularly hindered mesityl derivative
5e, not even traces of nitrocarbazoles can be observed, with total
substrate recovery.
The conditions for the reactions reported in Scheme 2 [2 equiv of
indole, 1 equiv of Zn(OAc)2 in EtOH, 40 ꢀC, followed by quenching in
water] have been extended to the series of 1,4-diaryl derivatives
5ael, spanning from electron-rich to electron-poor and hindered
aromatic moieties, and the results are reported on the left side of
Table 1.
The 3-nitrocarbazole 8 is the main product in all examples, in
a ratio, with respect to the 2-nitro derivative 9, ranging from 1.5 to
2, while the 2,3-dinitrocarbazole 10 is generally present only in
traces. Reactions are usually rather slow, particularly in the pres-
ence of steric hindrance (b, e, j) or of an electron-releasing
For the reaction under study we suggested3d a sequence of two
Michael additions of indole to the nitrovinylic moieties (the first
inter- and the second intra-molecular), each followed by restora-
tion of the aromaticity of the indole ring, eventually leading to the
double addition product, the tetrahydrocarbazole 11 (Scheme 3). As
recently reported in similar cases,9 the second participation of the
indole nucleus could involve the same C(3) rather than the C(2)
position, to generate a spiro intermediate that in acidic media can

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7423
Table 1
Results obtained in the reactions of 5ael with indole (2 equiv) and Zn(OAc)2 (1 equiv) at 40 ꢀC in EtOH, followed by water quenching, without or with an external oxidant added
(see text)a
Entry
Substrate: Ar
Time
Yields (%)b
Yields (%)b (with DDQ)
8
9
10
Total
8
9
10
Total
1
2
3
4
5
6
7
8
5a: Phenyl
5b: o-Tolyl
5c: m-Tolyl
5d: p-Tolyl
1 d
5 d
2 d
1 d
7 d
3 d
4 d
16 h
16 h
5 d
4 d
2 d
48
10d
36
50
d
24
trc
trc
8
7
d
72
10
66
87
d
22
6d
30
21
13
51
7
35
50
86
13
80
81
22
30
d
15
10
5e: Mesityl
5f: m-Anisyl
5g: p-Anisyl
5h: m-Cl-Phenyl
5i: p-Cl-Phenyl
5j: 1-Naphthyl
5k: 2-Naphthyl
5l: 2-Thienyl
39
53
39
45
41d
58
46
18
20
18
24
8
65
73
57
69
41
85
74
23
49
37
33
40d
55
32
15
20
21
18
32
5
70
74
68
69
60
91
77
trc
trc
trc
trc
trc
trc
10
18
20
11
29
9
10
11
12
27
28
25
16
a
The oxidant was added after the reaction time indicated in the third column and left to react 2e3 h before water quenching.
Yields of isolated compounds, unless otherwise indicated.
b
c
tr¼trace (<1%).
d
Overall 8D9 yield, in a 2:1 ratio as deduced by 1H NMR analysis.
Scheme 3. Proposed reaction pathways.
subsequently transform via a 1,2-migratory shift known as the
probability to be formed, 12B0 would be more effectively
resonance-stabilized than 12A0 thanks to a direct conjugation be-
tween the newly formed double bond and the pyrrole nitrogen.
Overall, then, the dihydrocarbazole with a nitro group at C(2), and
the 2-nitrocarbazole 9 produced, should be more easily formed: an
outcome, which is in contrast with the experimental evidence of
a ca. 2: 1 ratio in favor of 8 throughout.
A rationalization can possibly be found within path B of Scheme
3. Scheme 5 portrays a conceivable sequence for the oxidative de-
cay of intermediate 11 (accomplished, here again, by the nitrous
acid released along path A or by air) where 130 is formed, possibly
via 13. From 130, further oxidation would lead to dinitrocarbazole 10
while elimination would furnish to the 3-nitrocarbazole derivative
8 an additional chance to form.
Ciamician-Plancher rearrangement:10 a possibility, which cannot
be ruled out for our system.
As supported by indirect experimental evidence (for instance,
the occurrence that carbazoles 8e10 cannot be detected in the re-
action mixture by either TLC or 1H NMR analysis before quenching),
we suppose that 11, possibly stabilized, in EtOH, by the co-
ordination of the nitro groups with Zn(OAc)2, can effectively evolve
to 8e10 only after water addition and complex disruption due to
the increased medium polarity.
On the grounds of the structure of the isolated products and of
the tetrahydrocarbazole 11, two competitive pathways are con-
ceivable for the latter, namely HNO2 elimination (path A) and ox-
idation (path B) (Scheme 3).
As a matter of fact, the elimination of nitrous acid from 11 (an
occurrence already observed in similar systems of ours,3n charac-
terized by two nitro groups on adjacent sp3 carbon atoms) followed
by aromatization via oxidation either by air or by the just released
nitrous acid (as an endogenous oxidizing agent) would well justify
the formation of nitrocarbazoles 8 and 9. Furthermore, it should be
remarked that it could occur, for each of the two nitro groups on 11,
at the expense of either of the two adjacent protons, thus gener-
ating, at least in principle, two couples of isomers (Scheme 4).
While 12A and 12B, characterized by an ‘isolated’ double bond,
On the grounds of the oxidative steps involved in proposed
mechanism, we considered that the addition of an external oxidant
could possibly increase the yield of the dinitrocarbazoles 10, which
can only arise via two successive oxidations from the tetrahy-
drocarbazole 11. However, again due to the well-known sensitivity
of indole to oxidants, the timing for the introduction of DDQ had to
be properly evaluated.11 Thus, we chose to add the oxidant (3 equiv)
after the disappearance of the butadiene 5 (by TLC) and before
quenching with water (Table 1). The choice implicitly assumed that
a) the intramolecular process leading to 11 is fast, compared with
the intermolecular initial addition, and that b) most of the
would presumably have
a very similar stability and hence

7424
L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
Scheme 4. Hypothesized dihydrocarbazoles along the way to 8 and 9.
Scheme 5. Proposed route to 8 and 10 via initial oxidation of 11.
intermediate 11 still survives (most likely as a stabilized complex:
see above) prior to quenching. As a matter of fact, working-up the
reactions 2e3 h after the addition of DDQ afforded the data re-
ported on the right side of Table 1: the effect of DDQ, monitored by
the increase in the yield of 10 and appreciable throughout, is of
practical significance only in a few cases (a and d, where 10 be-
comes the main product, and, to a lower extent, c, f and l). Other
oxidants (nitrous acid itself, MCPBA or iodine) were also in-
vestigated, with meagre overall results and, furthermore, the ad-
ditional drawback of more complex final mixtures.
allowing to foresee a similar behavior. Thus, parallel experiments
were realized to test the reactivity of 30d and 40d, initially
employing the same conditions as those adopted for 5, e.g., EtOH in
the presence of 1 equiv of Zn(OAc)2 (Scheme 6).
It is noteworthy that, even when the effect on the yield of 10 is
more pronounced, the 8 to 9 ratio is scarcely altered, the former
always prevailing by a factor of ca. 2: one must then admit that the
access to 8 through the oxidationþelimination sequence of path B
(Scheme 5) is still competitive.
Besides the nitro group, Michael-type additions to vinyl moie-
ties can be effectively activated also by e.g., the sulfonyl group.12
Both derivatives 2 and 4 (Scheme 1), though, possess a methyl-
sulfonyl group which is not correctly positioned for a double-
Michael addition and, accordingly, our preliminary results de-
scribe the formation of open-chain addition products (Scheme 2).
Nonetheless, within the nitrobutadienes of the general struc-
tures 3 and 4 of Scheme 1, the ring-opening of 3-nitro-4-(phenyl-
sulfonyl)thiophene and further elaboration smoothly lead to
derivatives such as 30 and 40 (Scheme 6), whose functionalization
pattern, although unsymmetrical, more tightly resembles that of 5,
Scheme 6. Results of reaction with indole of 30d and 40d.
Surprisingly enough, sulfide 30d was recovered unchanged after
prolonged reaction times. Even more surprisingly, also 40d proved
to be unreactive, possibly due to its low solubility in the reaction
medium at 40e50 ꢀC. By heating the reaction mixture at reflux,
however, only the unexpected 14d was isolated in moderate yields,

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7425
whose structure does not include the indole moiety and is most
likely the result of a Nef reaction, within a more complex process
also encompassing a retro-Knoevenagel-like step. No further in-
vestigation in this direction was performed.
In the attempt to drive the reaction towards the desired double-
Michael process, a number of experimental conditions reported in
the literature for the conjugate addition to the nitrovinylic moiety
have been tested: iodine in diethyl ether,13 montmorillonite,14
CF3CH2OH (hereinafter TFE) in dichloromethane.15 As a partial
success was achieved only in the last case (Table 2, entry 1), we
eventually turned our attention to the employment of TFE as sol-
vent, without any added catalyst or promoter. The use of fluori-
nated alcohols [TFE or 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP)] in
organic reactions has been the subject of many recent studies,16 as
such solvents often allow reactions that usually require metal cat-
alysts. Their unique properties (high hydrogen-bonding donor
ability, low nucleophilicity, high ionizing power, lower pKa than
alcohols) make them suitable for e.g., FriedeleCrafts reactions,
DielseAlder (and others) cycloadditions, oxidations and isomeri-
zations. Easier isolation of products and convenient, eco-friendly
recycling of the solvent are further advantages of such media.
Chart 1.
The relatively ‘soft’ conditions of entry 3 were thus applied to
a series of substrates 40, obtaining the results reported in Table 3. It
should be observed that, due to the modest solubility of substrates,
the initial reactant concentration is in general necessarily low,
possibly justifying the rather long reaction time needed.
Table 3
Results obtained in the reactions of 40 with indole in TFE at 50 ꢀC
Entry
Substrate: Ar
Time (h)
Yields (%)a
15
16
17
Total
1
2
3
4
5
6
40 a: Phenylb
24
24
48
48
48
48
51
40
53
63
46
61
31
40
29
30
14
20
10c
10c
11c
6c
92
90
93
99
60
92
Table 2
40 d: p-Tolylb
Optimization of experimental conditions for the Scheme 7 reaction on 40d
(Ar¼p-Tol)
40 g: p-Anisylb
40 i: p-Cl-Phenyl
40 j: 1-Naphthyl
40 l: 2-Thienyl
trb,d
11
Entry Solvent
Indole T (ꢀC) Time (h) Yields (%)a
(equiv)
15d 16d 17d 18d Total
a
Yields of isolated compounds, unless otherwise indicated.
Interestingly enough, when the reactions are performed in HFIP (24 h, rt),
1
TFE/CH2Cl2 1:1
2
40
24
48
24
24
24
7
11 trb trb 59 70c
b
39 trb trb 49 88
a different distribution of products is observed: from 40 a, 15a: 13%, 16a: 57%, 17a:
2
3
4
5
6
TFE
TFE
TFE
TFE
TFE
2
2
2
4
4
40
50
60
60
80
38 40
6
84
90
85
75
69
9%; from 40 d, 15d: 36%, 16d: 55%, 17d: 9%; from 40 g, 15g: 21%, 16g: 72%, 17g: 4%.
40 40 10
32 43 10
c
Obtained as a mixture with the corresponding 15.
tr¼trace (<1%).
d
27 40
13 47
8
9
4
a
b
c
Yields of isolated compounds.
Notably, the tri-substituted carbazole 15 (whose structure was
unequivocally ascertained thanks to a single-crystal X-ray analysis
on 15d, Fig. 1) turns out to be the main product throughout, fol-
lowed by carbazole 16: the latter becoming prevalent when HFIP is
used as solvent (see footnote b of Table 3).
The 15:16:17 yield ratio is almost the same along the series,
evidencing that the effect of the aryl moiety is not significant. It
appears reasonable that, starting from the intermediate 19, 15 and
16 arise from a common precursor, possibly the dihydrocarbazole
20 (Scheme 8), the first by air oxidation and the second by MeSO2H
elimination. Thus, 15 is the result of an elimination (of benzensul-
finic acid)/aromatization process, and 16 of two consecutive sulfinic
acid eliminations.
As far as compound 17 is concerned, it could share with the
other two carbazole derivatives the intermediate 19, from which it
would form thanks to two consecutive eliminations (of nitrous and
methanesulfinic acids), or possibly take origin directly from 18,
through an addition-elimination process (a vinylic SN), followed by
elimination of nitrous acid.
tr¼trace (<1%).
Unreacted substrate also observed.
On these grounds, as the process under study possibly involves
the just-cited kinds of reactions, we treated substrate 40d with in-
dole (2 equiv) in TFE at 50 ꢀC; after 24 h, the final reaction mixture
was analyzed to reveal the presence of three different carbazole
derivatives (Scheme 7, compounds 15e17).
Different experimental conditions (Table 2) were also tried, in
the attempt to reduce times, improve yields and possibly modify
products distribution. Unfortunately, neither the variation of the
initial amount of indole (a larger excess making the reaction faster
but somewhat less clean: cf. entries 4 and 5) nor that of tempera-
ture (whose increase has a definite negative effect on the yield of
15d) proved to be effective. On the other hand, interestingly
enough, the less-polar medium of entry 1 (Table 2) leads to the
isolation of the unstable open-chain mono-addition product 18d
(Chart 1), whose yield decreases to the advantage mainly of car-
bazole 15d at prolonged reaction times.
Scheme 7. Carbazole derivatives from the reaction of 40d with indole in TFE.

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L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
the pattern of substitution as a 2-phenylsulfonyl-4-thienyl- rather
than 1-thienyl-3-phenylsulfonyl derivative, an alternative that
could have not been in principle excluded.
The undeniable efficacy of TFE as the reaction medium for the
reactions described on substrates 40 urged us to ascertain its effect
also on dinitrobutadienes 5: the latter were thus treated with
2 equiv of indole in TFE and, at the end of the reaction (as judged by
TLC/NMR disappearance of the substrate), the solvent was easily
removed and the crude analyzed. The results for the reactions on
substrates 5ael are reported in Table 4 (left). We were pleasantly
surprised discovering that in these conditions not only the re-
actions are notably faster, but the dinitrocarbazole 10 becomes the
main product throughout. This outcome, quite rewarding from the
practical/synthetic point of view, must be considered together with
the concurrent interesting evidence that 3-nitrocarbazoles 8 are
now secondary with respect to 2-nitrocarbazoles 9, whose yields
are in general only barely decreased with respect to those observed
in the original conditions (cf. Table 1, left). One must then admit
that a) as hypothesized above, 9 is more easily formed than 8
within path A (see Scheme 4 and relevant observations in the text),
b) the decreased yield of 8 should be essentially ascribed to a de-
pletion of its formation via elimination from 130 to the advantage of
10 (see Scheme 5), and c) the still competitive path A most likely
provides the endogenous oxidant for path B.
Further confirmation of the advanced mechanistic hypotheses
was indirectly obtained when adding DDQ as an external oxidant
after disappearance of the substrate: the obtained results, reported
on the right side of Table 4, show a modest improvement in the
yield of 10 (the increase never amounting to more than 12%), the
yields of the two mono-nitrated products remaining almost un-
changed. It can be deduced that most of 11 evolves spontaneously
in the reaction medium, and the late-added oxidant intercepts only
the amount of 11 not yet evolved. Accordingly, a somewhat lower
increase is observed for the anisyl derivatives, namely the more
prone to undergo a ‘spontaneous’ oxidation.
Fig. 1. ORTEP of 15d.
It should be noted that, due to the very low quantities obtained,
always as mixtures with the corresponding product 15, it was not
possible to isolate and fully characterize compounds 17 (but for
17l). For this compound, an HSQC spectrum allowed to ascertain
Scheme 8. A hypothesized pathway to compounds 15e17.

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7427
Table 4
Results obtained in the reactions of 5ael with indole in TFE, without or with an external oxidant added (see text)a
Entry
Substrate: Ar
Time
Yields (%)b
Yields (%)b (with DDQ)
8
9
10
Total
8
9
10
Total
1
2
3
4
5
6
7
8
5a: Phenyl
5b: o-Tolyl
4 h
4 d
1 d
4 h
7 d
2 d
2 d
16 h
16 h
3d
14
11c
10
13
d
6
7
8
12
30c
18
11
30
39
12
37
48
d
83
23
70
88
d
12
7c
8
27
51
14
49
56
90
21
77
93
5c: m-Tolyl
23
27
d
20
25
5d: p-Tolyld
5e: Mesityl
12
5f: m-Anisyl
5g: p-Anisyl
5h: m-Cl-Phenyl
5i: p-Cl-Phenyl
5j: 1-Naphthyl
5k: 2-Naphthyl
5l: 2-Thienyl
14
15
13
21
53
57
50
40
29
39
51
73
79
71
73
59
87
80
5
8
9
10
30c
15
10
14
15
18
17
57
58
55
49
39
48
57
76
81
82
76
76
89
82
9
10
11
12
2 d
1 d
30
18
26
15
a
The oxidant was added after the reaction time indicated in the third column and left to react 2e3 h before work-up.
Yields of isolated compounds, unless otherwise indicated.
b
c
Overall 8 þ 9 yield, in a 1:2 ratio as deduced by 1H NMR analysis.
d
The reaction in HFIP (24 h, rt) produced the following mixture: 8d 20%, 9d 40%; 10d 20%.
Even if the system could probably be further improved, it should
major product (57%) together with minor quantities (25%) of the
diaminocarbazole 24d. After the addition of some fresh catalyst,
supplementary 24 h of hydrogenation produced the diamine in 78%
yields. The classical Zn/HCl, Sn/HCl and SnCl2∙2H2O systems were
also tested, with no significant modification of relative yields and,
on the other hand, similar or lower overall yields and/or longer
reaction times.
be said that, with the exception of hindered substrates, these last
conditions bring to 50e60% yields of the dinitro derivatives 10
throughout: a satisfactory result, especially when considering the
multi-step nature of the process.
As an example of applicative developments, fluorescent carba-
zole derivatives can be simply obtained by reduction of the nitro
group (a well-known fluorescence quencher) in nitrocarbazoles.17
Thus, by catalytic hydrogenation of compound 8d (Scheme 9) the
corresponding 3-aminocarbazole derivative 21d was obtained in
high yields (92%) within 48 h, while compound 9d was likewise
satisfactorily (90%) reduced to 22 within a shorter time (24 h). The
more facile reduction of the 2-nitro versus the 3-nitro group has
been attributed to the involvement of the latter within a vinylogous
nitroenaminic moiety.18 Consistently, when the same reaction
conditions were applied to 10d, after 24 h the reaction mixture
contained the 1,4-diaryl-2-amino-3-nitrocarbazole 23d as the
The fluorescence of 21d is clearly demonstrated by the spectra
reported in Fig. 2.
3. Conclusions
Altogether, the results herein represent a further significant
breakthrough of our nitrobutadienic building blocks into the field of
N-heterocyclic synthesis. In particular, a new, one-pot procedure is
illustrated, which, through a sequence of inter- and intramolecular
steps and a final aromatization, builds-up a functionalized benzene
Scheme 9. Results of hydrogenation on compounds 8de10d.

7428
L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
Fig. 2. Absorption spectra of compounds 8d and 21d.
ring onto an indole precursor, giving access to interesting carbazole
derivatives. On both 40 (Scheme 1, 4: Z¼H, Y¼SO2Ph) and 5 (which,
for electronic reasons, have proved to be most suited among other
nitrobutadienes: cf. Scheme 1), the process is actually characterized
by the formation of mixtures of carbazoles, originating by means of
competitive pathways whereby elimination and/or oxidation pro-
cesses eventually lead to full aromatization of the newly condensed
heterocycle.
As a matter of fact, two sets of competition are operative herein,
namely i) elimination versus oxidation (by air, endogenous nitrous
acid, or a purposely added oxidant) and, ii) within elimination,
cleavage of different leaving groups (NO2, PhSO2, MeSO2), or of
identical leaving groups from different positions.
according to Cadogan reaction,19 to obtain new, more complex,
angular, polycyclic derivatives.
4. Experimental section
4.1. Materials and methods
1H NMR and 13C NMR spectra were recorded with a Varian
Mercury 300 Plus spectrometer, at 300 and 75 MHz, respectively;
chemical shifts (TMS as internal reference) are reported as d values
(ppm). Gas chromatographyemass spectrometry (GCeMS) was
performed on HP 5890/5971 (EI 70 eV) system equipped with
Thus, as far as the latter competition is concerned, it should be
noticed that the poly-functionality of our dienes, which is essential
for the hypothesized Michael-type addition (Scheme 3) and/or
vinylic substitution sequence (Scheme 8), on the other hand rep-
resents, in some way, a drawback whenever it is not possible to
identify operative conditions, which would perform a fully selective
process leading to one or the other of the reported products. A
practical significance is nonetheless guaranteed herein by the oc-
currence that a satisfactory product selectivity (at least allowing to
easily isolate the main product) can be reached indeed by a choice
of the reaction conditions. Thus, as far as reactions on the sym-
metrical dinitrobutadiene 5 are concerned, two sets of conditions
provide preferential access to the 3-nitroderivative 8 [Zn(OAc)2,
EtOH, 40 ꢀC, then water quenching: see Table 1] or to the 2,3-
dinitroderivative 10 [TFE, 50 ꢀC, then DDQ: see Table 4]. On the
other hand, as far as the unsymmetrical 40 system is concerned, the
use of TFE at 50 ꢀC is the only practicable set of conditions among
those tested, leading to a 40e60% yield of the trisubstituted car-
bazole 15 throughout. Needless to say, when possible, the use of TFE
represents a clean (the solvent can be recovered by distillation at
the end of the reaction), metal-free, atom-economic and opera-
tionally simple process.
a HP-1 MS capillary column (12 mꢁ0.2 mm i.dꢁ0.33
mm). High-
resolution mass spectra (HRMS) were obtained with a Agilent
MSD TOF mass spectrometer, and recorded in positive ion mode
with an electrospray (ESI) source. Melting points were determined
€
with a Buchi 535 apparatus and are uncorrected. IR spectra were
recorded on a Perkin Elmer Spectrum 65 FTIR and wave numbers
are reported in cmꢂ1. Absorption spectra were recorded using
a Perkin Elmer Lambda9 UV/VIS/NIR Spectrophotometer, while
Fluorescence spectra were recorded (at the excitation wave-
lengths of 254 nm and 440 nm) with the Perkin Elmer MPF-44A
Fluorescence Spectrophotometer, and were normalized using
Rhodamine B in PMMA as reference standard. Petroleum ether
and light petroleum refer to the fractions with bp 40e60 ꢀC and
80e100 ꢀC, respectively. Silica gel 230e400 mesh was used for
column chromatography, all solvents being distilled before use.
Tetrahydrofuran (THF) was purified by standard methods and
distilled over potassium benzophenone ketyl before use. All other
commercially available reagents were used as received. 4-
Chlorophenylmagnesium bromide, 3-methylphenylmagnesium
chloride, and 3-methoxyphenylmagnesium bromide were com-
mercial THF or Et2O solutions titrated just before use.
Compounds 30 and 40a,d,g,j,l have been already described,20
while 30i and 40i are new compounds, prepared according to the
same procedure, in 83% and 48% yield, respectively.
Finally, the nitro group that characterizes all of the obtained
derivatives can be further modified, e.g., by reduction to amine or,

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7429
4.1.1. (E,E)-1-(4-Chlorophenyl)-4-methylthio-2-nitro-3-
was purified by column chromatography using hexane/ethyl ace-
tate (10:1) to give 8, 9 and 10.
For experiments performed with the oxidant, DDQ (3 equiv) was
added after the ascertained reaction time, and the mixture kept
under magnetic stirring at 50 ꢀC for additional 2 h.
phenylsulfonyl-1,3-butadiene (30i). Yellow solid, mp 141e142 ꢀC
(ethanol). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.54 (3H, s),
7.27e7.33 (2H, m), 7.38e7.47 (4H, m), 7.50e7.57 (1H, m), 7.78e7.85
(2H, m), 8.24 (1H, s), 8.27 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm)
d
17.7, 110.0, 125.3, 128.2, 129.2, 129.3, 131.9, 133.7, 138.3, 139.5, 139.6,
139.7, 156.3. IR (ATR): ṽ (cmꢂ1) 1646, 1589, 1550, 1524, 1489, 1446,
1405, 1315, 1306, 1284, 1210, 1144, 1083, 1046, 1012. HRMS (ESI) m/z
calcd [MþNH4]þ C17H18ClN2O4S2 413.0391 found 413.0390.
4.3.1. 1,4-Diphenyl-3-nitro-9H-carbazole (8a).3d Yellow solid, mp
175e176 ꢀC (petroleum ether/dichloromethane). 1H NMR (CDCl3,
300 MHz):
1.8 Hz), 7.33e7.68 (10H, m), 7.68e7.78 (2H, m), 8.22 (1H, s), 8.65
(1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 111.2, 120.8, 122.2, 122.9,
d (ppm) 6.62 (1H, d, J 8.1 Hz), 6.96 (1H, ddd, J 8.2, 6.4,
4.1.2. (E,E)-1-(4-Chlorophenyl)-4-methylsulfonyl-2-nitro-3-
d
phenylsulfonyl-1,3-butadiene (40i). Yellow solid, mp 209e210 ꢀC
123.2, 123.7, 124.3, 127.2, 128.4, 128.5, 128.8, 128.9, 129.1, 129.8,
132.5, 136.7, 136.8, 139.3, 140.5, 141.8. HRMS (ESI) m/z calcd [MþH]þ
C24H17N2O2 365.1285, found 365.1280.
(ethanol). 1H NMR (DMSO-d6, 300 MHz):
d (ppm) 3.30 (3H, s),
7.32e7.38 (2H, m), 7.43e7.53 (4H, m), 7.62e7.70 (1H, m), 7.71e7.83
(2H, m), 8.55 (1H, s), 8.67 (1H, s). 13C NMR (DMSO-d6, 75 MHz):
d
(ppm) 47.4, 133.2, 134.2, 135.0, 137.9, 140.5, 141.5, 142.0, 142.4,
4.3.2. 1,4-Diphenyl-2-nitro-9H-carbazole (9a).3d Yellow solid, mp
196e197 ꢀC (petroleum ether/dichloromethane). 1H NMR (CDCl3,
144.9, 147.2, 150.8 (two isochronous carbons). IR (ATR): ṽ (cmꢂ1
)
1661, 1586, 1527, 1448, 1334, 1322, 1309, 1285, 1214, 1165, 1156,
1145, 1093, 1088, 1041, 1013. HRMS (ESI) m/z calcd [MþNH4]þ
C17H18ClN2O6S2 445.0289, found 445.0291.
300 MHz):
d
(ppm) 7.05 (1H, t, J 7.4 Hz), 7.33e7.73 (13H, m), 7.82
(ppm) 111.1, 117.2,
(1H, s), 8.16 (1H, s). 13C NMR (CDCl3, 75 MHz):
d
119.4, 120.3, 122.2, 123.4, 124.1, 127.8, 128.6, 128.8, 128.9, 129.2,
129.6, 129.9, 134.1, 137.2, 139.2, 141.4, 145.2, 165.4. HRMS (ESI) m/z
calcd [MþH]þ C24H17N2O2 365.1285, found 365.1289.
Compounds 5a,1b b,1c d,1c e,21 g,1c h,1c i,3b j,1c k,22 l,1c have been
already described, while 5c and 5f are new compounds, prepared
according to a reported procedure,1b in 89% and 93% yield,
respectively.
4.3.3. 2,3-Dinitro-1,4-diphenyl-9H-carbazole (10a). Yellow solid,
mp 293e294 ꢀC (petroleum ether/dichloromethane). 1H NMR
4.1.3. (1E,3E)-1,4-Bis(3-methylphenyl)-2,3-dinitro-1,3-butadiene
(CDCl3, 300 MHz):
1.8 Hz), 7.37e7.76 (12H, m), 8.40 (1H, s). 1H NMR (DMSO-d6,
300 MHz): (ppm) 6.60 (1H, d, J 8.1 Hz), 7.02 (1H, t, J 7.7 Hz), 7.47 (1H,
t, J7.8Hz), 7.53e7.70 (11H,m),12.03(1H, s).13C NMR(CDCl3, 75MHz):
(ppm) 111.7,119.0,121.7,122.8,123.3,128.6,129.0,129.0,129.1,129.3,
d (ppm)6.80(1H, d, J 8.2 Hz), 7.03 (1H, ddt, J 7.9, 6.1,
(5c). Yellow solid, mp 96e97 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.28 (6H, s),
d
7.14e7.24 (8H, m), 8.45 (2H, s). 13C NMR (CDCl3, 75 MHz):
d
(ppm)
21.4, 127.4, 129.4, 129.7, 131.5, 133.3, 139.3, 140.1, 141.6. IR (ATR): ṽ
(cmꢂ1) 1670, 1619, 1601, 1582, 1517, 1314, 1245, 1176, 1164, 1095,
1058. HRMS (ESI) m/z calcd [MþNH4]þ C18H20N3O4 342.1448, found
342.1450.
d
129.4, 129.7, 130.0, 130.1, 130.1, 131.2, 131.4, 133.5, 137.8, 141.4. HRMS
(ESI) m/z calcd [MþH]þ C24H16N3O4 410.1135, found 410.1129.
4.3.4. 1,4-Bis(2-methylphenyl)-3-nitro-9H-carbazole (8b) and 1,4-
Bis(2-methylphenyl)-2-nitro-9H-carbazole (9b). Yellow oil. 1H NMR
(CDCl3, 300 MHz): d (ppm) 2.45 (3H of 9b, s), 2.44 (3H of 8b, s), 2.47
4.1.4. (1E,3E)-1,4-Bis(3-methoxyphenyl)-2,3-dinitro-1,3-butadiene
(5f). Yellow solid, mp 105e106 ꢀC (ethanol). 1H NMR (CDCl3,
300 MHz):
d
(ppm) 3.72 (6H, s), 6.86 (2H, t, J 2.1 Hz), 6.92e7.01 (4H,
(3H of 9b, s), 2.50 (3H of 8b, s), 6.97 (1H of 8b, ddd, J 8.2, 6.3, 1.9 Hz),
7.03 (1H of 9b, t, J 7.0 Hz), 7.25e7.65 (11H of 9bþ11H of 8b), 7.78 (1H
of 9b, s), 8.16 (1H of 9b, s), 8.18 (1H of 8b, s), 8.62 (1H of 8b, s). (8b)
HRMS (ESI) m/z calcd [MþH]þ C26H21N2O2 393.1598, found
393.1594. (9b) HRMS (ESI) m/z calcd [MþH]þ C26H21N2O2 393.1598,
found 393.1595.
m), 7.26 (2H, dd, J 8.2, 7.7 Hz), 8.45 (2H, s). 13C NMR (CDCl3,
75 MHz):
d (ppm) 55.6, 115.4, 118.7, 123.3, 130.7, 131.1, 140.6, 141.6,
160.3. IR (ATR): ṽ (cmꢂ1) 1694, 1586, 1537, 1489, 1457, 1432, 1288,
1038. HRMS (ESI) m/z calcd [MþNH4]þ C18H20N3O6 374.1347, found
374.1349.
4.2. General procedure for the reaction of dinitrobutadienes 5
with indole in EtOH
4.3.5. 1,4-Bis(2-methylphenyl)-2,3-dinitro-9H-carbazole
(10b). Yellow oil. 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.37 (3H, s),
2.40 (3H, s), 6.87 (1H, d, J 8.0 Hz), 7.02 (1H, td, J 7.5, 1.5 Hz),
7.24e7.56 (10H, m), 8.45 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm)
To a stirred suspension of 5 (0.5 mmol) in ethanol (8 mL) at
40 ꢀC, indole (1.1 mmol) and zinc acetate (0.5 mmol) were added.
The mixture was stirred at 40 ꢀC for the time necessary to ensure
completion of reaction, then poured into water and extracted with
dichloromethane; the organic extracts were dried over Na2SO4 and
the solvent was removed under reduced pressure. The residue was
purified by column chromatography using hexane/ethyl acetate
(10:1) to give 8, 9 and 10.
For experiments performed with the oxidant, DDQ (3 equiv) was
added after the ascertained reaction time before the aqueous
quenching, and the mixture kept under magnetic stirring at 40 ꢀC
for additional 2e3 h.
d
19.7, 19.8, 111.4, 119.5, 120.2, 121.5, 121.5, 122.4, 126.4, 126.5, 127.5,
127.8, 129.5, 129.9, 130.1, 130.1, 130.3, 130.8, 134.4, 134.6, 135.4,
135.9, 139.0, 139.2, 140.7, 142.7. HRMS (ESI) m/z calcd [MþH]þ
C26H20N3O4 438.1448, found 438.1446.
4.3.6. 1,4-Bis(3-methylphenyl)-3-nitro-9H-carbazole
solid; mp 110e111 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 2.45 (3H, s), 2.51 (3H, s), 6.67 (1H, d, J
8.1 Hz), 6.97 (1H, ddd, J 8.2, 6.5, 1.8 Hz), 7.27 (1H, d, J 5.4 Hz),
7.29e7.44 (5H, m), 7.41e7.56 (4H, m), 8.19 (1H, s), 8.64 (1H, s). 13
NMR (CDCl3, 75 MHz): (ppm) 21.7, 21.8, 111.2, 120.8, 122.2, 123.0,
(8c). Yellow
d
C
d
123.1,123.9,124.4,125.5,125.5,127.1,128.9,128.9,129.1,129.3,129.6,
129.6, 132.6, 136.6, 136.8, 138.7, 139.4, 139.7, 140.5, 141.9 HRMS (ESI)
m/z calcd [MþH]þ C26H21N2O2 393.1598, found 393.1594.
4.3. General procedure for the reaction of dinitrobutadienes 5
with indole in TFE
Indole (1.1 mmol) was added to a stirred suspension of 5
(0.5 mmol) in TFE (8 mL) at 50 ꢀC. The mixture was stirred at 50 ꢀC
for the time necessary to ensure completion of reaction (TLC), and
then the solvent was removed under reduced pressure. The residue
4.3.7. 1,4-Bis(3-methylphenyl)-2-nitro-9H-carbazole
solid; mp 164e165 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 2.46 (3H, s), 2.48 (3H, s), 7.04 (1H, ddd, J
8.3, 6.4, 1.8 Hz), 7.26e7.43 (6H, m), 7.43e7.50 (3H, m), 7.56 (2H, d, J
(9c). Yellow
d

7430
L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
8.1 Hz), 7.79 (1H, s), 8.17 (1H, s). 13C NMR (CDCl3, 75 MHz):
d
(ppm)
(CDCl3, 300 MHz): d (ppm) 3.87 (3H, s), 3.88 (3H, s), 7.00e7.12 (4H,
21.7, 21.7, 111.1, 117.1, 119.4, 120.3, 122.3, 123.5, 124.1, 125.9, 126.3,
127.6, 128.7, 129.3, 129.4 (two isochronous carbons), 129.6, 129.9,
134.0, 137.3, 138.6, 138.7, 139.2, 139.3, 141.4, 145.2 HRMS (ESI) m/z
calcd [MþH]þ C26H21N2O2 393.1598, found 393.1592.
m), 7.17e7.30 (3H, m), 7.37e7.44 (2H, m), 7.46e7.53 (2H, m),
7.55e7.62 (1H, m), 7.81 (1H, s), 8.23 (1H, s). 13C NMR (CDCl3,
75 MHz):
d (ppm) 55.6, 56.0, 111.4, 113.3, 113.8, 114.1, 114.2, 114.7,
118.0, 121.4, 121.5, 122.3, 123.0, 126.1, 129.1, 129.5, 130.7, 132.9, 133.1,
133.9, 135.5, 138.0, 138.8, 143.5, 159.9, 160.7. HRMS (ESI) m/z calcd
[MþH]þ C26H21N2O4 425.1496, found 425.1493.
4.3.8. 1,4-Bis(3-methylphenyl)-2,3-dinitro-9H-carbazole
(10c). Yellow solid; mp 228e229 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.45 (3H, s), 2.47 (3H,
s), 6.83 (1H, d, J 8.2 Hz), 7.04 (1H, ddd, J 8.2, 6.0, 2.1 Hz), 7.27e7.55
(10H, m), 8.48 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 21.8, 21.8,
4.3.14. 1,4-Bis(3-methoxyphenyl)-2,3-dinitro-9H-carbazole
(10f). Yellow solid; mp 217e218 ꢀC (petroleum ether/dichloro-
d
methane). 1H NMR (CDCl3, 300 MHz):
d (ppm) 3.85 (3H, s), 3.86 (3H,
111.7, 119.1, 121.6, 122.8, 122.8, 123.4, 126.1, 126.1, 128.5, 129.2, 129.4,
129.5, 129.9, 130.4, 130.9, 131.1, 131.5, 132.2, 133.4, 137.0, 137.8, 139.1,
139.9, 141.4. HRMS (ESI) m/z calcd [MþH]þ C26H20N3O4 438.1448,
found 438.1451.
s), 6.90 (1H, d, J 8.1 Hz), 7.00e7.16 (7H, m), 7.45 (2H, dd, J 6.1, 1.3 Hz),
7.51 (2H, ddd, J 8.4, 7.6, 3.3 Hz), 8.55 (1H, s). 13C NMR (CDCl3,
75 MHz):
d (ppm) 55.5, 55.6, 111.4, 113.8, 113.9, 114.1, 114.1, 115.5,
121.5, 121.5, 122.4, 124.3, 125.0, 126.3, 129.2, 129.5, 130.3, 130.8,
135.9, 136.8, 137.0, 139.2, 142.7, 147.2, 160.1, 160.7. HRMS (ESI) m/z
calcd [MþH]þ C26H20N3O6 470.1347, found 470.1342.
4.3.9. 1,4-Bis(4-methylphenyl)-3-nitro-9H-carbazole (8d).3d Yellow
solid; mp 213e214 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz):
d
(ppm) 2.49 (3H, s), 2.53 (3H, s), 6.74 (1H, d, J
4.3.15. 1,4-Bis(4-methoxyphenyl)-3-nitro-9H-carbazole (8g). Yellow
solid; mp 183e184 ꢀC (petroleum ether/dichloromethane). 1H NMR
8.1 Hz), 6.98 (1H, ddd, J 8.3, 6.0, 2.1 Hz), 7.29e7.47 (8H, m), 7.62 (2H,
d, J 8.1 Hz), 8.16 (1H, s), 8.60 (1H, br s). 1H NMR (DMSO-d6,
(CDCl3, 300 MHz):
d (ppm) 3.92 (3H, s), 3.94 (3H, s), 6.79 (1H, d, J
300 MHz):
d
(ppm) 2.46 (3H, s), 2.49 (3H, s), 6.55 (1H, d, J 8.0 Hz),
8.1 Hz), 6.99 (1H, ddd, J 8.1, 6.2, 2.0 Hz), 7.12 (4H, ddd, J 10.5, 6.3,
2.3 Hz), 7.31e7.47 (4H, m), 7.65 (2H, d, J 8.7 Hz), 8.12 (1H, s), 8.65
6.92 (1H, t, J 7.4 Hz), 7.32 (2H, d, J 8.0 Hz), 7.35 (1H, m part. over-
lapped with the previous), 7.42 (2H, d, J 8.0 Hz), 7.46 (2H, d, J 7.9 Hz),
7.59 (1H, d, J 8.1 Hz), 7.69 (2H, d, J 8.0 Hz), 8.06 (1H, s), 11.81 (1H, s).
(1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 55.5, 55.6, 111.2, 114.5,
115.2,120.7,121.9, 123.0,123.4,123.9,124.0, 127.1,128.6,129.1, 129.7,
129.7, 131.7, 139.4, 140.5, 142.4, 159.6, 160.0. HRMS (ESI) m/z calcd
[MþH]þ C26H21N2O4 425.1496, found 425.1495.
13C NMR (CDCl3, 75 MHz):
d (ppm) 21.6, 21.8, 111.2, 120.8, 122.2,
123.1, 123.2, 124.0, 124.3, 127.2, 128.4, 128.5, 129.9, 130.6, 132.5,
133.6, 134.0, 138.1, 138.9, 139.4, 140.5, 142.2. GCeMS m/z 392. HRMS
(ESI) m/z calcd [MþH]þ C26H21N2O2 393.1598, found 393.1597.
4.3.16. 1,4-Bis(4-methoxyphenyl)-2-nitro-9H-carbazole (9g). Yellow
solid; mp 172e173 ꢀC (petroleum ether/dichloromethane). 1H NMR
4.3.10. 1,4-Bis(4-methylphenyl)-2-nitro-9H-carbazole (9d).3d Yellow
solid; mp 124e125 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz):
7.1 Hz), 7.33e7.45 (8H, m), 7.52e7.64 (3H, m), 7.77 (1H, s), 8.16 (1H,
s). 1H NMR (DMSO-d6, 300 MHz):
(ppm) 2.45 (3H, s), 2.47 (3H, s),
7.01 (1H, t, J 7.7 Hz), 7.35e7.49 (8H, m), 7.53e7.61 (4H, m), 11.29 (1H,
s). 13C NMR (CDCl3, 75 MHz):
(ppm) 21.6 (two isochronous car-
(CDCl3, 300 MHz):
1.6 Hz), 7.07e7.17 (4H, m), 7.32e7.48 (4H, m), 7.55e7.66 (3H, m),
7.74 (1H, s), 8.19 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 55.5,
d (ppm) 3.91 (3H, s), 3.95 (3H, s), 7.06 (1H, t, J
d
(ppm) 2.50 (3H, s), 2.52 (3H, s), 7.05 (1H, t, J
d
55.6, 111.1, 114.3, 115.0, 117.1, 118.7, 120.2, 122.4, 123.4, 125.9, 127.6,
129.9, 130.2, 130.4, 131.6, 136.8, 139.0, 141.4, 145.5, 159.9, 160.0.
HRMS (ESI) m/z calcd [MþH]þ C26H21N2O4 425.1496, found
425.1498.
d
d
bons), 111.1, 117.1, 119.2, 120.2, 122.3, 123.5, 124.0, 127.6, 128.8, 129.1,
129.6, 130.3, 131.0, 136.3, 137.1, 138.4, 138.7, 138.8, 141.4, 145.4.
GCeMS m/z 392. HRMS (ESI) m/z calcd [MþH]þ C26H21N2O2
393.1598, found 393.1594.
4.3.17. 1,4-Bis(4-methoxyphenyl)-2,3-dinitro-9H-carbazole
(10g). Yellow solid; mp 228e229 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d (ppm) 3.91 (3H, s), 3.94 (3H,
s), 6.94 (1H, d, J 8.2 Hz), 7.05 (1H, ddd, J 8.3, 6.4, 1.9 Hz), 7.10 (2H, d, J
4.3.11. 1,4-Bis(4-methylphenyl)-2,3-dinitro-9H-carbazole
2.4 Hz), 7.12 (2H, d, J 2.5 Hz), 7.37e7.52 (6H, m), 8.44 (1H, s). 13C
NMR (CDCl3, 75 MHz): d (ppm) 55.2, 56.4, 111.5, 118.5, 119.7, 121.5,
122.4, 122.9, 129.0, 129.4, 130.1, 130.2, 130.4, 130.7, 130.8, 130.8,
136.1, 139.2, 140.7, 142.4, 160.8, 161.8. HRMS (ESI) m/z calcd [MþH]þ
C26H20N3O6 470.1347, found 470.1341.
(10d).3d Yellow solid; mp 267e268 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.49 (3H, s), 2.52 (3H,
s), 6.90 (1H, d, J 8.1 Hz), 7.05 (1H, td, J 7.4, 1.6 Hz), 7.25e7.58 (10H,
m), 8.40 (1H, s). 1H NMR (DMSO-d6, 300 MHz):
(ppm) 2.47 (3H, s),
d
2.50 (3H, s), 6.71 (1H, d, J 8.5 Hz), 7.04 (1H, t, J 7.7 Hz), 7.39e7.53
(9H, m), 7.61 (1H, d, J 8.3 Hz), 11.97 (1H, s). 13C NMR (CDCl3,
4.3.18. 1,4-Bis(3-chlorophenyl)-3-nitro-9H-carbazole (8h).3d Orange
solid; mp 257e258 ꢀC (petroleum ether/dichloromethane). 1H NMR
75 MHz):
d (ppm) 21.6, 21.7, 111.5, 118.9, 121.4, 122.8, 122.8, 123.3,
128.1,128.4,128.7, 128.8,130.0,130.4,130.6,131.3, 137.2,137.7,139.5,
140.1, 140.7, 141.3. HRMS (ESI) m/z calcd [MþH]þ C26H20N3O4
438.1448, found 438.1442.
(CDCl3, 300 MHz):
2.0 Hz), 7.28e7.67 (9H, m), 7.72 (1H, m), 8.23 (1H, s), 8.66 (1H, s). 13
NMR (CDCl3, 75 MHz): (ppm) 111.2,117.6,119.6,120.4,122.2,123.5,
d (ppm) 6.67 (1H, d, J 8.1 Hz), 7.03 (1H, td, J 7.6,
C
d
124.4, 126.8 (two isochronous carbons), 126.8, 127.0, 127.0, 127.3,
127.8, 127.9, 128.1, 128.2, 128.2, 128.3, 128.5, 128.6, 129.4, 131.7,
133.3, 133.3, 133.6, 133.7, 136.7, 137.2, 139.1, 141.5, 145.2 (several
signals are split, presumably due to the presence of two con-
formers). HRMS (ESI) m/z calcd [MþH]þ C24H15Cl2N2O2 433.0505,
found 433.0502.
4.3.12. 1,4-Bis(3-methoxyphenyl)-3-nitro-9H-carbazole (8f). Yellow
solid; mp 173e174 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz):
d (ppm) 3.85 (3H, s), 3.93 (3H, s), 6.74 (1H, d, J
8.1 Hz), 6.95e7.14 (5H, m), 7.17e7.33 (1H, m), 7.35e7.44 (2H, m),
7.45e7.62 (3H, m), 8.22 (1H, s), 8.69 (1H, s). 13C NMR (CDCl3,
75 MHz):
d (ppm) 55.6, 56.2, 111.4, 113.4, 113.7, 113.9, 114.1, 121.5,
121.5, 122.4, 123.9, 124.9, 125.1, 125.2, 126.1, 129.4, 129.5, 129.7,
130.8, 131.5, 137.1, 137.3, 139.2, 146.8, 160.0, 160.5. HRMS (ESI) m/z
calcd [MþH]þ C26H21N2O4 425.1496, found 425.1492.
4.3.19. 1,4-Bis(3-chlorophenyl)-2-nitro-9H-carbazole (9h).3d Yellow
solid; mp 207e208 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz):
7.30e7.76 (11H, m), 7.84 (1H, s), 8.14 (1H, s). 13C NMR (CDCl3,
75 MHz): (ppm) 111.4, 117.2, 118.4, 120.8, 121.8, 123.3, 124.3, 127.2,
127.4, 128.2, 128.9, 129.0, 129.2, 129.3, 130.3, 130.9, 134.9, 135.4,
d (ppm) 7.10 (1H, ddd, J 8.3, 6.3, 2.1 Hz),
4.3.13. 1,4-Bis(3-methoxyphenyl)-2-nitro-9H-carbazole (9f). Yellow
solid; mp 164e165 ꢀC (petroleum ether/dichloromethane). 1H NMR
d

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7431
135.8, 135.9,138.6,140.8,141.6,144.8. HRMS (ESI) m/z calcd [MþH]þ
122.5, 123.0, 123.3, 123.8, 124.5, 126.2, 126.6, 126.6, 126.8, 127.1,
127.1,127.2,127.2, 127.7, 128.1,128.2,128.3,128.5,128.8,129.8,132.4,
133.2,133.2,133.7, 133.8,134.1,134.2,139.6,140.6,142.2. HRMS (ESI)
m/z calcd [MþH]þ C32H21N2O2 465.1598, found 465.1593.
C24H15Cl2N2O2 433.0505, found 433.0501.
4.3.20. 1,4-Bis(3-chlorophenyl)-2,3-dinitro-9H-carbazole
(10h). Orange solid; mp 208e209 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 6.83 (1H, d, J 8.2 Hz),
7.10 (1H, ddt, J 7.7, 6.1, 1.7 Hz), 7.37e7.66 (10H, m), 8.45 (1H, s). 13
NMR (CDCl3, 75 MHz): (ppm) 111.9, 117.9,122.1,122.4,123.0,123.2,
4.3.27. 1,4-Bis(2-naphthyl)-2-nitro-9H-carbazole
solid; mp 252e253 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 6.99 (1H, ddd, J 8.2, 6.7, 1.4 Hz),
(9k). Orange
C
d
d
127.3, 127.3, 127.4, 129.1, 129.2, 129.3, 130.1, 130.1, 130.2, 130.6, 130.8,
131.4, 132.7, 135.1, 135.4, 136.0, 137.6, 141.5. HRMS (ESI) m/z calcd
[MþH]þ C24H14Cl2N3O4 478.0356, found 478.0358.
7.30e7.47 (2H, m), 7.51e7.69 (6H, m), 7.83 (1H, dd, J 8.3, 1.7 Hz),
7.90e8.04 (6H, m), 8.08 (2H, dd, J 8.4, 2.3 Hz), 8.19 (1H, m), 8.22 (1H,
s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 111.2, 117.6,119.6,120.4,122.2,
123.5,124.4,126.8,126.8,127.0,127.0,127.3,127.8,127.9,127.9, 128.1,
128.2, 128.2, 128.3, 128.5, 128.6, 129.4, 131.7, 133.3, 133.3, 133.6,
133.7, 136.7, 137.2, 139.1, 141.5, 145.2. HRMS (ESI) m/z calcd [MþH]þ
C32H21N2O2 465.1598, found 465.1595.
4.3.21. 1,4-Bis(4-chlorophenyl)-3-nitro-9H-carbazole
solid; mp 255e256 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 6.71 (1H, d, J 7.9 Hz), 7.03 (1H, ddd, J 8.2,
6.2, 2.0 Hz), 7.36e7.48 (4H, m), 7.55e7.64 (4H, m), 7.68 (2H, d, J
8.2 Hz), 8.20 (1H, s), 8.73 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm)
(8i). Yellow
d
d
4.3.28. 1,4-Bis(2-naphthyl)-2,3-dinitro-9H-carbazole (10k). Yellow
solid; mp 252e253 ꢀC (petroleum ether/dichloromethane). 1H NMR
111.4, 117.7, 119.4, 121.1, 122.2, 122.8, 123.4, 127.5, 129.5, 129.9 (two
isochronous carbons), 130.1, 130.8, 131.5, 134.5, 135.1, 139.1, 139.3,
140.6, 141.5. HRMS (ESI) m/z calcd [MþH]þ C24H15Cl2N2O2
433.0505, found 433.0501.
(CDCl3, 300 MHz):
5.4, 2.7 Hz), 7.34e7.47 (2H, m), 7.55e7.73 (7H, m), 7.86e8.14 (7H,
m), 8.61 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 111.6, 119.1,
d (ppm) 6.78 (1H, d, J 8.1 Hz), 6.93 (1H, ddd, J 8.2,
d
121.7, 122.7, 123.0, 123.3, 125.8, 126.1, 126.6, 127.0, 127.3, 127.4, 127.7,
128.1, 128.2 (two isochronous carbons), 128.5, 128.6, 128.6, 128.8,
129.1, 130.0, 130.0, 130.9, 131.1, 131.3, 133.4, 133.5, 133.6, 133.7, 138.0,
141.4. HRMS (ESI) m/z calcd [MþH]þ C32H20N3O4 510.1448, found
510.1444.
4.3.22. 1,4-Bis(4-chlorophenyl)-2-nitro-9H-carbazole
solid; mp 222e223 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 7.09 (1H, ddt, J 7.9, 6.6,1.2 Hz), 7.36e7.50
(3H, m), 7.50e7.69 (8H, m), 7.81 (1H, s), 8.12 (1H, s). 13C NMR (CDCl3,
75 MHz): (ppm) 111.4, 117.3, 118.6, 120.7, 122.0, 123.4, 124.3, 128.2,
(9i). Yellow
d
d
129.3, 130.0, 130.4, 130.6, 132.5, 134.9, 135.2, 136.2, 137.6, 138.8,
141.6, 145.0. HRMS (ESI) m/z calcd [MþH]þ C24H15Cl2N2O2
433.0505, found 433.0499.
4.3.29. 1,4-Bis(2-thienyl)-3-nitro-9H-carbazole (8l). Orange solid;
mp 165e166 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): d (ppm) 6.79 (1H, d, J 8.3 Hz), 7.06 (1H, ddd, J 8.2,
6.5, 1.7 Hz), 7.15 (1H, dd, J 3.5, 1.2 Hz), 7.25e7.29 (1H, m), 7.44 (2H,
dd, J 8.4, 1.7 Hz), 7.51 (2H, ddd, J 5.1, 4.3, 1.2 Hz), 7.61 (1H, dd, J 5.1,
4.3.23. 1,4-Bis(4-chlorophenyl)-2,3-dinitro-9H-carbazole
(10i). Yellow solid; mp 239e240 ꢀC (petroleum ether/dichloro-
1.2 Hz), 8.27 (1H, s), 8.94 (1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm)
methane). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 6.87 (1H, d, J 8.1 Hz),
7.10 (1H, t, J 7.4 Hz), 7.44e7.54 (6H, m), 7.55e7.66 (4H, m), 8.38 (1H,
s). 13C NMR (CDCl3, 75 MHz):
(ppm) 111.8, 118.0, 119.1, 122.0,122.4,
111.5,119.6,121.0,121.5,121.5,122.4,123.5,125.0,128.8,129.0,129.0,
129.2, 129.3, 130.9, 130.9, 137.4, 138.4, 139.2, 139.7, 142.2. HRMS
(ESI) m/z calcd [MþH]þ C20H13N2O2S2 377.0413, found 377.0410.
d
123.1, 128.9, 129.3, 129.7, 130.2, 130.4 (two isochronous carbons),
130.4, 130.5, 131.7, 136.0, 136.6, 137.6, 139.9, 141.4. HRMS (ESI) m/z
calcd [MþH]þ C24H14Cl2N3O4 478.0356, found 478.0358.
4.3.30. 1,4-Bis(2-thienyl)-2-nitro-9H-carbazole (9l). Orange solid;
mp 186e187 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): d (ppm) 7.07 (1H, ddd, J 8.1, 6.9, 1.3 Hz), 7.24 (1H,
4.3.24. 1,4-Bis(1-naphthyl)-3-nitro-9H-carbazole (8j) and 1,4-Bis(1-
dd, J 5.2, 3.5 Hz), 7.28 (1H, d, J 5.7 Hz), 7.37 (1H, dd, J 3.5, 1.2 Hz), 7.41
(1H, dd, J 6.9, 1.2 Hz), 7.46 (2H, d, J 4.4 Hz), 7.48 (1H, dd, J 5.1, 1.2 Hz),
7.56 (1H, d, J 7.7 Hz), 7.73 (1H, dd, J 7.9, 0.9 Hz), 8.67 (1H, s). 13C NMR
naphthyl)-2-nitro-9H-carbazole (9j). Yellow solid. 1H NMR (CDCl3,
300 MHz): d (ppm) 6.17 (1H of 8j, dd, J 3.8, 8.1 Hz), 6.60e6.73 (1H of
9j and 1H of 8j, m), 7.11e7.70 (15H of 9j and 12H of 8j, m), 7.90e8.02
(4H of 9j and 4H of 8j, m), 8.14 (1H of 8j, s), 8.35 (1H of 8j, s). (8j).
HRMS (ESI) m/z calcd [MþH]þ C32H21N2O2 465.1598, found
465.1595. (9j) HRMS (ESI) m/z calcd [MþH]þ C32H21N2O2 465.1598,
found 465.1593.
(CDCl3, 75 MHz): d (ppm) 111.4, 116.5, 117.1, 119.3, 121.4, 121.5, 122.3,
127.3, 128.8, 128.9, 129.0, 129.2, 129.2, 130.7, 131.3, 134.2, 134.4,
138.8, 140.7, 143.1. HRMS (ESI) m/z calcd [MþH]þ C20H13N2O2S2
377.0413, found 377.0416.
4.3.31. 1,4-Bis(2-thienyl)-2,3-dinitro-9H-carbazole
solid; mp 283e284 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 6.93 (1H, dt, J 8.3, 1.1 Hz), 7.13 (1H, ddd, J
(10l). Orange
4.3.25. 1,4-Bis(1-naphthyl)-2,3-dinitro-9H-carbazole (10j). Yellow
solid; mp 253e254 ꢀC (petroleum ether/dichloromethane). 1H NMR
d
(CDCl3, 300 MHz):
7.3 Hz), 7.17e7.72 (12H, m), 7.94e8.20 (4H, m), 8.47 (1H, s). 13C NMR
(CDCl3, 75 MHz): (ppm) 119.8, 121.5, 121.5, 122.4, 123.5, 125.3,
d
(ppm) 6.23 (1H, d, J 8.1 Hz), 6.77 (1H, app. t, J
8.3, 6.2, 2.0 Hz), 7.23e7.32 (3H, m), 7.34e7.38 (1H, m), 7.44e7.56
(2H, m), 7.61e7.71 (2H, m), 8.74 (1H, s). 13C NMR (CDCl3, 75 MHz):
d
d (ppm) 111.4, 120.1, 120.8, 121.5, 121.5, 122.4, 125.6, 125.9, 128.8
125.6, 126.0, 126.4, 126.5, 126.9, 127.3, 127.5, 127.8 (two isochronous
carbons), 127.9, 128.2, 128.4, 128.7, 130.8, 131.6, 132.1, 132.4, 133.1,
134.3, 135.0, 136.1, 139.2, 140.8, 144.1. HRMS (ESI) m/z calcd [MþH]þ
C32H20N3O4 510.1448, found 510.1449.
(two isochronous carbons), 129.2 (two isochronous carbons), 130.8,
133.1, 133.7, 133.9, 135.4, 137.1, 139.2, 141.3. HRMS (ESI) m/z calcd
[MþH]þ C20H12N3O4S2 422.0264, found 422.0260.
4.3.32. 1-(4-Methylphenyl)-3-(phenylsulfonyl)propan-2-one
4.3.26. 1,4-Bis(2-naphthyl)-3-nitro-9H-carbazole
solid; mp 225e226 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 6.62 (1H, d, J 8.0 Hz), 6.87 (1H, ddd, J 8.1,
(8k). Orange
(14d). White solid; mp 87e88 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d (ppm) 2.33 (3H, s), 3.93 (2H,
d
s), 4.15 (2H, s), 6.97e7.11 (2H, m), 7.11e7.20 (2H, m), 7.49e7.68 (2H,
7.0, 1.2 Hz), 7.30e7.48 (2H, m), 7.51e7.70 (5H, m), 7.81e7.96 (3H, m),
7.96e8.07 (3H, m), 8.12 (2H, dd, J 8.4, 5.4 Hz), 8.24 (1H, s), 8.37
m), 7.62e7.77 (1H, m), 7.82e7.98 (2H, m). 13C NMR (CDCl3, 75 MHz):
d
(ppm) 21.3, 50.8, 65.6, 76.8, 77.3, 77.7, 128.6, 129.4, 129.6, 129.7,
(1H, s), 8.75 (1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 111.2, 120.9,
130.0, 134.6, 137.6, 138.8, 196.2. GCeMS: Rt 5.43, m/z 288(12)

7432
L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
[Mþꢃ], 147(100), 141(15), 105(87), 77(50). HRMS (ESI) m/z calcd
[MþH]þ C16H17O3S 289.0893, found 289.0892.
d (ppm) 21.5, 109.4, 110.9, 120.5, 122.7, 122.8, 123.4, 126.9, 128.0,
129.6, 133.5, 133.6, 137.9, 140.5, 141.3, 141.6 (two isochronous car-
bons). GCeMS: Rt 9.84, m/z 302(100) [Mþꢃ], 257(31), 254(31),
241(35). HRMS (ESI) m/z calcd [MþH]þ C19H15N2O2 303.1128, found
303.1133.
4.4. General procedure for the reaction of nitrobutadienes 40
with indole in TFE
Indole (0.25 mmol) was added to a stirred suspension of 40
(0.123 mmol) in TFE (6 mL) at 50 ꢀC. The mixture was stirred at
50 ꢀC for the time necessary to ensure completion of reaction (see
Table 3), and then the solvent was removed under reduced pres-
sure. The residue was purified by column chromatography using
petroleum ether/ethyl acetate (10:1) to give 15, 16 and 17. Com-
pounds 17 (minor) are usually in mixture with 15 (major): it is
usually possible to obtain by crystallization only 15 as pure sam-
ples. Only in the case of Ar¼thienyl, compound 17l could be isolated
and fully characterized.
4.4.7. 4-(4-Methylphenyl)-1-phenylsulfonyl-9H-carbazole
(17d). Isolated by chromatographic column as a mixture with 15d:
only a few signals in the 1H NMR spectrum can be assigned with
confidence: 1H NMR (CDCl3, 300 MHz):
d (ppm) 7.95e8.04 (2H, m),
8.07 (1H, d, J 1.6 Hz), 8.57 (1H, s). GCeMS: Rt 17.18, m/z 397(100)
[Mþꢃ], 281(18), 241(38), 78(41), 64(34). HRMS (ESI) m/z calcd
[MþH]þ C25H20NO2S 398.1209, found 398.1205.
4.4.8. 1-Methylsulfonyl-4-(4-methoxyphenyl)-3-nitro-9H-carbazole
(15g). Yellow solid, mp 251e252 ꢀC (ethanol). 1H NMR (CDCl3,
300 MHz): d (ppm) 3.30 (3H, s), 3.95 (3H, s), 6.80 (1H, d, J 8.1 Hz), 7.07
4.4.1. (E)-3-(4-(Methylsulfonyl)-2-nitro-3-(phenylsulfonyl)-1-(p-
(1H, t, J 7.6 Hz), 7.12 (2H, d, J 8.7 Hz), 7.31 (2H, d, J 8.7 Hz), 7.49 (1H, t, J
tolyl)but-3-en-1-yl)-1H-indole (18d). Unstable intermediate iso-
7.5 Hz), 7.56 (1H, d, J 8.1 Hz), 8.62 (1H, s),10.02 (1H, s). 13C NMR (CDCl3,
lated as an oil; 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.17 (3H, s), 3.14
75MHz):d(ppm)45.0,55.4,111.9,114.6,119.7,121.7,122.3,122.5,123.0,
(3H, s), 4.63 (1H, d, J 14.7 Hz), 4.87 (1H, d, J 14.7 Hz), 6.47 (1H, s),
6.91e6.99 (5H, m), 7.03e7.08 (2H, m), 7.15 (1H, d, J 3.0 Hz), 7.17 (1H,
d, J 2.9 Hz), 7.18e7.37 (3H, m), 7.76e7.92 (2H, m), 7.93 (1H, s).
126.0, 126.8, 128.4, 129.1, 137.4, 138.0, 140.7, 141.4, 160.0. GCeMS: Rt
7.70, m/z 396(66) [Mþꢃ], 228(70), 114(61), 100(100). HRMS (ESI) m/z
calcd [MþH]þ C20H17N2O5S 397.0853, found 397.0854.
4.4.2. 1-Methylsulfonyl-3-nitro-4-phenyl-9H-carbazole
4.4.9. 4-(4-Methoxyphenyl)-3-nitro-9H-carbazole
(16g). Yellow
(ppm)
(15a). Yellow solid, mp 242e243 ꢀC (ethanol). 1H NMR (CDCl3,
solid, mp 170e171 ꢀC (ethanol). 1H NMR (CDCl3, 300 MHz):
d
300 MHz):
m), 7.35e7.43 (2H, m), 7.45e7.52 (1H, m), 7.53e7.64 (4H, m), 8.69
(1H, s), 10.04 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 45.0, 111.9,
d
(ppm) 3.31 (3H, s), 6.61 (1H, d, J 8.2 Hz), 6.93e7.13 (1H,
3.94 (3H, s), 6.77 (1H, d, J 8.0 Hz), 6.99 (1H, ddd, J 8.2, 6.7, 1.5 Hz),
7.06e7.15 (2H, m), 7.28e7.50 (5H, m), 8.15 (1H, d, J 8.9 Hz), 8.52 (1H,
d
s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 55.4, 109.4, 110.9, 114.4, 120.5,
119.9, 121.8, 122.4, 122.5, 122.9, 125.7, 127.6, 128.5, 128.9, 129.2,
135.1, 137.6, 138.2, 140.7, 140.8. GCeMS: Rt 6.01, m/z 366(100)
[Mþꢃ], 257(54), 241(88), 240(71), 107(38). HRMS (ESI) m/z calcd
[MþH]þ C19H15N2O4S 367.0747, found 367.0752.
122.6, 122.8, 123.0, 123.4, 127.0, 128.5, 129.4, 133.1, 140.4, 141.2,
141.9, 159.5. GCeMS: Rt 5.46, m/z 318(96) [Mþꢃ], 258(40), 228(74),
114(100), 100(60). HRMS (ESI) m/z calcd [MþH]þ C19H15N2O3
319.1077, found 319.1076.
4.4.3. 3-Nitro-4-phenyl-9H-carbazole (16a). Yellow solid, mp
158e159 ꢀC (dichloromethane/petroleum ether). 1H NMR (CDCl3,
4.4.10. 4-(4-Methoxyphenyl)-2-phenylsulfonyl-9H-carbazole
(17g). Isolated by chromatographic column as a mixture with 15g:
only a few signals in the 1H NMR spectrum can be assigned with
300 MHz):
7.31e7.52 (5H, m), 7.52e7.71 (3H, m), 8.21 (1H, d, J 8.9 Hz), 8.58 (1H,
s). 13C NMR (CDCl3, 75 MHz):
(ppm) 109.6, 111.0, 120.5, 122.7,
d (ppm) 6.60 (1H, d, J 8.1 Hz), 6.96 (1H, t, J 7.4 Hz),
confidence: 1H NMR (CDCl3, 300 MHz):
d (ppm) 7.97e8.03 (1H, m),
d
8.05 (1H, d, J 1.6 Hz), 8.30 (1H, s). GCeMS: Rt 21.18, m/z 413(100)
[Mþꢃ], 281(29), 228(35), 110(27), 96(35), 77(61), 64(67). HRMS
(ESI) m/z calcd [MþH]þ C25H20NO3S 414.1158, found 414.1153.
123.3, 127.0, 128.1, 128.2, 128.9, 130.9, 133.5, 136.7, 140.5, 141.2, 141.4
(two isochronous carbons). GCeMS: Rt 4.56, m/z 288(100) [Mþꢃ],
241(78), 240(35), 106(31). HRMS (ESI) m/z calcd [MþH]þ
C18H13N2O2 289.0972, found 289.0967.
4.4.11. 4-(4-Chlorophenyl)-1-methylsulfonyl-3-nitro-9H-carbazole
(15i). Yellow solid, mp 236e238 ꢀC (ethanol). 1H NMR (CDCl3,
4.4.4. 4-Phenyl-2-phenylsulfonyl-9H-carbazole (17a). Isolated by
chromatographic column as a mixture with 15a: only a few signals
in the 1H NMR spectrum can be assigned with confidence: 1H NMR
300 MHz):
8.2, 6.8, 1.4 Hz), 7.31e7.43 (2H, m), 7.45e7.74 (4H, m), 8.69 (1H, s),
10.04 (1H, s). 13C NMR (CDCl3, 75 MHz):
(ppm) 45.0, 112.0, 120.2,
d (ppm) 3.30 (3H, s), 6.70 (1H, d, J 8.1 Hz), 7.09 (1H, ddd, J
d
(CDCl3, 300 MHz):
d
(ppm) 7.97e8.04 (2H, m), 8.10 (1H, d, J 1.6 Hz),
122.0, 122.2, 122.5, 122.7, 125.6, 128.7, 129.2, 129.6, 133.5, 135.1,
136.9, 137.6, 140.8 (two isochronous carbons). GCeMS: Rt 11.42, m/z
400(100) [Mþꢃ], 370(41), 275(32), 256(38), 240(45),100(19). HRMS
(ESI) m/z calcd [MþH]þ C19H14ClN2O4S 401.0357, found 401.0352.
8.61 (1H, s). GCeMS: Rt 11.40, m/z 383(100) [Mþꢃ], 241(99),
230(63), 128(35), 77(98). HRMS (ESI) m/z calcd [MþH]þ C24H18NO2
S 384.1053, found 384.1055.
4.4.5. 4-(4-Methylphenyl)-1-methylsulfonyl-3-nitro-9H-carbazole
4.4.12. 4-(4-Chlorophenyl)-3-nitro-9H-carbazole (16i). Yellow solid,
mp 221e223 ꢀC (petroleum ether/dichloromethane). 1H NMR
(15d). Yellow solid, mp 250e252 ꢀC (ethanol). 1H NMR (CDCl3,
300 MHz):
d
(ppm) 2.53 (3H, s), 3.29 (3H, s), 6.73 (1H, d, J 8.1 Hz),
(CDCl3, 300 MHz):
6.5, 1.7 Hz), 7.30e7.41 (2H, m), 7.38e7.46 (2H, m), 7.49 (1H, d, J
9.0 Hz), 7.52e7.58 (2H, m), 8.22 (1H, d, J 9.0 Hz), 8.62 (1H, s). 13
NMR (CDCl3, 75 MHz): (ppm) 109.9, 111.1, 120.8, 122.5, 122.8,
d (ppm) 6.69 (1H, d, J 8.0 Hz), 7.02 (1H, ddd, J 8.2,
6.97e7.18 (1H, m), 7.28 (2H, d, J 8.0 Hz), 7.40 (2H, d, J 8.0 Hz),
7.45e7.57 (2H, m), 8.63(1H, s), 9.98 (1H, s).13C NMR(CDCl3, 75MHz):
C
d
(ppm) 21.6, 45.0, 111.8, 119.7, 121.7, 122.4, 122.5, 123.0, 125.7, 127.5,
d
128.4, 129.9, 131.9, 137.5, 138.4, 138.8, 140.7, 141.2. GCeMS: Rt 12.15,
m/z 380(100) [Mþꢃ], 271(33), 254(59),113(32). HRMS (ESI) m/z calcd
[MþH]þ C20H17N2O4S 381.0904, found 381.0907.
123.0, 127.2, 128.8, 129.2, 129.7, 132.2, 134.2, 135.2, 140.5, 141.2,
141.4. GCeMS: Rt 9.45, m/z 322(100) [Mþꢃ], 292(85), 257(58),
241(77), 114(54), 106(52), 96(48). HRMS (ESI) m/z calcd [MþH]þ
C18H12ClN2O2 323.0582, found 323.0580.
4.4.6. 4-(4-Methylphenyl)-3-nitro-9H-carbazole (16d). Yellow solid,
mp 211e212 ꢀC (ethanol). 1H NMR (CDCl3, 300 MHz):
d
(ppm) 2.51
4.4.13. 4-(4-Chlorophenyl)-2-phenylsulfonyl-9H-carbazole
(17i). Isolated by chromatographic column as a mixture with 15i:
only a few signals in the 1H NMR spectrum can be assigned with
(3H, s), 6.90e7.06 (1H, m), 6.98 (1H, ddd, J 8.2, 6.7, 1.6 Hz), 7.19e7.52
(7H, m), 8.17 (1H, d, J 8.9 Hz), 8.59 (1H, s). 13C NMR (CDCl3, 75 MHz):

L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
7433
confidence: 1H NMR (CDCl3, 300 MHz):
d
(ppm) 7.96e8.04 (1H, m),
the system deaerated and kept under hydrogen atmosphere and
magnetic stirring. The advancement of the reaction was checked by
TLC. At the end of the reaction, the mixture was filtered, the catalyst
washed with dichloromethane and the solvent removed under
reduced pressure. For the reactions on 8d and 9d the crude was
crystallized and pure 21d and 22d were obtained, respectively; in
the case of 10d the crude was purified by column chromatography
using petroleum ether/ethyl acetate (10:1) to give 23d and 24d, in
57% and 25% yields, respectively.
8.11 (1H, d, J 1.5 Hz), 8.61 (1H, s). GCeMS: Rt 20.93, m/z 417(13)
[Mþꢃ], 264(40), 241(91), 213(22), 158(17), 77(100). HRMS (ESI) m/z
calcd [MþH]þ C24H17ClNO2S 418.0663, found 418.0660.
4.4.14. 1-Methylsulfonyl-4-(1-naphthyl)-3-nitro-9H-carbazole
(15j). Yellow solid, mp 254e255 ꢀC (ethanol). 1H NMR (CDCl3,
300 MHz): d (ppm) 3.37 (3H, s), 6.12 (1H, d, J 8.0 Hz), 6.82 (1H, ddd, J
8.2, 7.1, 1.0 Hz), 7.27e7.32 (2H, m), 7.36e7.46 (2H, m), 7.48e7.56
(2H, m), 7.66 (1H, dd, J 8.3, 7.1 Hz), 8.02 (1H, d, J 8.2 Hz), 8.10 (1H, d, J
8.2 Hz), 8.83 (1H, s), 10.03 (1H, s). 13C NMR (CDCl3, 75 MHz):
4.5.1. 1,4-Bis(4-methylphenyl)-9H-carbazol-3-amine (21d). White
solid; mp 230e231 ꢀC (petroleum ether/dichloromethane). 1H
d
(ppm) 45.1, 111.7, 120.2, 121.9, 122.2, 122.7, 122.8, 124.5, 125.2,
125.7, 126.3, 126.5, 127.0, 128.4, 128.7, 129.3, 130.9, 132.8, 133.6,
137.0, 137.7, 140.7, 141.4. GCeMS: Rt 13.64, m/z 416(57) [Mþꢃ],
308(26), 291(100), 146(46), 131(28). HRMS (ESI) m/z calcd [MþH]þ
C23H17N2O4S 417.0904, found 417.0900.
NMR (CDCl3, 300 MHz): d (ppm) 2.47 (3H, s), 2.52 (3H, s), 3.46
(2H, s), 6.85 (1H, t, J 7.3 Hz), 6.93 (1H, d, J 7.9 Hz), 6.98 (1H, s),
7.18e7.33 (2H, m), 7.33e7.49 (6H, m), 7.61 (2H, d, J 7.6 Hz), 8.10
(1H, s). 1H NMR (DMSO-d6, 300 MHz):
d (ppm) 2.42 (3H, s), 2.47
(3H, s), 4.43 (2H, s), 6.65e6.78 (2H, m), 6.95 (1H, s), 7.16 (1H, ddd, J
8.2, 5.5, 2.8 Hz), 7.26e7.34 (2H, m), 7.35e7.46 (5H, m), 7.54e7.63
4.4.15. 4-(1-Naphthyl)-3-nitro-9H-carbazole (16j). Yellow solid. 1H
NMR (CDCl3, 300 MHz):
d
(ppm) 6.10 (1H, d, J 8.1 Hz), 6.74 (1H, ddd,
(2H, m), 10.66 (1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 21.4,
J 8.2, 7.2, 1.1 Hz), 7.33e7.38 (1H, m), 7.41 (1H, dt, J 8.4, 1.0 Hz),
7.44e7.51 (2H, m), 7.53 (1H, dd, J 5.7, 3.3 Hz), 7.58 (1H, d, J 8.9 Hz),
7.63 (1H, dd, J 8.3, 7.0 Hz), 7.71 (1H, dd, J 5.7, 3.3 Hz), 7.99 (1H, d, J
21.6, 110.5, 115.4, 118.7, 121.1, 122.4, 122.9, 123.5, 124.8, 125.4,
128.4, 130.0, 130.1, 130.3, 131.7, 134.4, 136.2, 137.4, 137.4, 137.6,
140.3. HRMS (ESI) m/z calcd [MþH]þ C26H23N2 363.1856, found
363.1851.
8.2 Hz), 8.06 (1H, d, J 8.4 Hz), 8.36 (1H, d, J 8.9 Hz), 8.58 (1H, s). 13
C
NMR (CDCl3, 75 MHz):
d (ppm) 109.8, 110.8, 120.7, 122.6, 123.0,
125.0, 125.4, 125.8, 126.2, 126.6, 127.0, 128.4, 128.6, 128.8, 130.9,
131.6, 132.4, 133.6, 134.5, 140.4, 141.5, 167.8. GCeMS: Rt 10.84, m/z
338(100) [Mþꢃ], 309(49), 292(76), 146(65), 131(46). HRMS (ESI) m/
z calcd [MþH]þ C22H15N2O2 339.1128, found 339.1126.
4.5.2. 1,4-Bis(4-methylphenyl)-9H-carbazol-2-amine (22d). White
solid; mp 231e232 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz):
d (ppm) 2.47 (3H, s), 2.49 (3H, s), 3.85 (2H, s),
6.60 (1H, s), 6.92 (1H, t, J 7.0 Hz), 7.12e7.28 (2H, m), 7.33 (2H, d, J
7.6 Hz), 7.36e7.45 (3H, m), 7.48 (2H, d, J 7.6 Hz), 7.56 (2H, d, J 7.6 Hz),
4.4.16. 1-Methylsulfonyl-3-nitro-4-(2-thienyl)-9H-carbazole
7.80 (1H, s). 1H NMR (DMSO-d6, 300 MHz):
d (ppm) 2.43 (6H, s),
(15l). Yellow solid, mp 288e289 ꢀC (ethanol). 1H NMR (DMSO-d6,
4.73 (2H, s), 6.51 (1H, s), 6.77 (1H, t, J 7.6 Hz), 7.07 (1H, t, J 7.5 Hz),
300 MHz):
d (ppm) 3.50 (3H, s), 6.60 (1H, d, J 8.0 Hz), 7.09 (1H, t, J
7.18 (1H, d, J 8.0 Hz), 7.27e7.50 (9H, m), 10.26 (1H, s). 13C NMR
7.6 Hz), 7.25 (1H, dd, J 3.6, 1.2 Hz), 7.34 (1H, dd, J 5.1, 3.5 Hz), 7.52
(1H, t, J 7.6 Hz), 7.81 (1H, d, J 8.1 Hz), 7.93 (1H, dd, J 5.0, 1.3 Hz), 8.57
(CDCl3, 75 MHz): d (ppm) 21.5, 21.5, 108.4, 110.0, 111.0, 113.3, 119.0,
121.3, 123.9, 124.1, 129.1, 129.2, 130.1, 130.7, 132.0, 137.23, 137.7,
137.9, 138.3, 139.5, 140.3, 141.9. HRMS (ESI) m/z calcd [MþH]þ
C26H23N2 363.1856, found 363.1858.
(1H, s), 12.35 (1H, s). 13C NMR (DMSO-d6, 75 MHz):
d (ppm) 43.8,
113.7, 121.6, 121.7, 122.1, 122.2, 122.5, 126.4, 128.2, 128.4, 128.8,
129.0, 129.8, 134.5, 137.0, 141.0, 142.3. GCeMS: Rt 10.31, m/z 372(51)
[Mþꢃ], 354(84), 342(96), 246(100), 207(80), 179(68), 87(78). HRMS
(ESI) m/z calcd [MþH]þ C17H13N2O4S2 373.0311, found 373.0316.
4.5.3. 1,4-Bis(4-methylphenyl)-3-nitro-9H-carbazol-2-amine
(23d). Orange solid; mp 156e157 ꢀC (petroleum ether/dichloro-
methane). 1H NMR (CDCl3, 300 MHz):
d (ppm) 2.48 (3H, s), 2.49 (3H,
4.4.17. 3-Nitro-4-(2-thienyl)-9H-carbazole (16l). Yellow solid. 1H
NMR (CDCl3, 300 MHz): d (ppm) 6.79 (1H, d, J 7.9 Hz), 6.91e7.12 (2H,
s), 5.02 (2H, s), 6.67 (1H, dd, J 8.0, 1.0 Hz), 6.87 (1H, ddd, J 8.2, 6.7,
1.5 Hz), 7.11e7.24 (2H, m), 7.29e7.38 (4H, m), 7.39e7.48 (4H, m),
m), 7.14 (1H, dd, J 3.5, 1.2 Hz), 7.42e7.47 (2H, m), 7.51 (1H, d, J
8.9 Hz), 7.61 (1H, dd, J 5.1, 1.2 Hz), 8.18 (1H, d, J 8.8 Hz), 8.53 (1H, s).
7.75 (1H, s). 1H NMR (DMSO-d6, 300 MHz):
d (ppm) 2.46 (3H, s),
2.46 (3H, s), 5.17 (2H, s), 6.43e6.52 (1H, m), 6.73e6.83 (1H, m), 7.16
(1H, td, J 8.1, 7.6, 1.2 Hz), 7.25e7.34 (3H, m), 7.34e7.44 (4H, m),
13C NMR (CDCl3, 75 MHz):
d (ppm) 110.4, 111.0, 119.0, 119.9, 120.8,
122.6,122.8,123.0,125.6,127.0,127.1,127.4,127.4,135.9,140.5,141.0.
GCeMS: Rt 8.81, m/z 294(70) [Mþꢃ], 276(98), 264(78), 246(69),
218(92), 165(100), 88(94). HRMS (ESI) m/z calcd [MþH]þ
C16H11N2O2S 295.0536, found 295.0533.
7.44e7.52 (2H, m), 10.68 (1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm)
21.0 (two isochronous carbons), 108.5, 111.3, 113.0, 119.1, 120.2,
123.0, 125.1, 128.3, 129.4, 130.3, 130.4, 130.5, 131.2, 133.4, 137.4,
137.6, 137.7, 140.9, 141.3, 141.5. HRMS (ESI) m/z calcd [MþH]þ
C26H22N3O2 408.1707, found 408.1702.
4.4.18. 2-Phenylsulfonyl-4-(2-thienyl)-9H-carbazole
solid; mp 101e103 ꢀC (petroleum ether/dichloromethane). 1H NMR
(CDCl3, 300 MHz): (ppm) 7.04e7.12 (1H, m), 7.22 (1H, dd, J 5.1,
(17l). Yellow
4.5.4. 1,4-Bis(4-methylphenyl)-9H-carbazol-2,3-diamine
d
(24d). White solid; mp 273e275 ꢀC (petroleum ether/dichloro-
3.5 Hz), 7.32 (1H, dd, J 3.5, 1.2 Hz), 7.42e7.59 (6H, m), 7.62e7.72 (1H,
m), 7.73 (1H, d, J 1.6 Hz), 7.97e8.04 (2H, m), 8.11 (1H, d, J 1.6 Hz),
methane). 1H NMR (CDCl3, 300 MHz):
d (ppm) 2.48 (3H, d, J 1.6 Hz),
2.53 (3H, d, J 1.9 Hz), 3.32 (4H, br s), 6.84 (1H, m), 7.13e7.37 (2H, m),
8.57 (1H, s). 13C NMR (CDCl3, 75 MHz):
d (ppm) 108.6, 109.5, 118.6,
7.37e7.52 (9H, m), 8.09 (1H, s). 1H NMR (DMSO-d6, 300 MHz):
119.3, 120.1, 121.6, 124.9, 125.9, 125.9, 126.1, 126.3, 126.3, 127.8,
129.3, 131.5, 136.2, 137.4, 138.6, 139.6, 140.5. GCeMS: Rt 31.05, m/z
389 (100) [Mþꢃ], 247(33), 236(27), 204(14), 77(13). HRMS (ESI) m/z
calcd [MþH]þ C22H16NO2S2 390.0617, found 390.0613.
d
(ppm) 2.44 (3H, s), 2.47 (3H, s), 4.02 (4H, s), 6.49e6.69 (2H, m),
6.92e7.05 (1H, m), 7.21e7.48 (9H, m), 9.98 (1H, s). 13C NMR (CDCl3,
75 MHz): (ppm) 16.1, 16.3, 106.7, 108.0, 114.4, 116.0, 116.7, 117.7,
d
118.5, 124.1, 124.3, 124.5, 124.6, 124.9, 126.0, 126.1, 128.0, 128.9,
134.4, 134.5, 135.7, 137.4. HRMS (ESI) m/z calcd [MþH]þ C26H24N3
378.1965, found 378.1961.
4.5. General procedure for the reduction of nitrocarbazoles
8de10d to aminocarbazoles 21de24d
4.5.5. X-ray crystallographic study of compound 15d. C20H16N2O4S,
M¼380.42, pale yellow prism with irregular shape and dimensions
In a two-neck round-bottom flask, the substrate dissolved in
dichloromethane was added with Pd/C (100% weight equivalent),
ꢁ
0.30ꢁ0.40ꢁ0.55 mm. Triclinic, space group P 1, a¼9.470(1) A,

7434
L. Bianchi et al. / Tetrahedron 71 (2015) 7421e7435
¼101.51(1)ꢀ,
b
¼103.78(1)ꢀ,
CCDC, 12 Union Road, Cambridge CB2 IEZ, UK [fax: þ44 (0) 1223
ꢁ
ꢁ
b¼10.467(1) A, c¼11.679(1) A,
a
3
ꢁ
g
¼107.65(1)ꢀ, V¼1024.2(2) A , Z¼2, F(000)¼396, dcalcd¼1.234
336033 or e-mail: deposit@ccdc.cam.ac.uk].
g/cm3,
m
(MoK
a
)¼0.184 mmꢂ1. Crystals were grown from ethyl
acetate solution.
Acknowledgements
Intensity data were collected at 295 K on a Bruker-Nonius
MACH3 diffractometer (graphite monochromated Mo K radia-
a
Financial support was provided by grants from Ministero del-
tion):
u-q ,
scans, scan width 1.12ꢀ, minimum speed 0.96ꢀ minꢂ1
ꢀ
l’Istruzione, dell’Universita e della Ricerca (MIUR-Roma, PRIN
qmax¼29ꢀ; 5697 total measured reflections, 5383 independent re-
2010FPTBSH) and Genoa University (PRA 2013). We thank Dr. Elena
Cotella and Dr. Mara Guidi for skilful contributions with the ex-
perimental work. Dr. Maria Isabel Martinez Espinoza is also grate-
fully acknowledged for performing fluorescence analyses.
flections of which 4132 with I>4 s(I).
The structure was solved with the SIR2014 program,23 with all
non-hydrogen atoms clearly revealed from the first Fourier map.
The refinement was accomplished by means of full-matrix least
squares cycles using the SHELXL program,24 the correct assign-
ment of atomic species being possible on the basis of bond dis-
tances and Uiso values. After some cycles of anisotropic
refinement of the heavier atoms, all hydrogen atoms were ob-
tained in subsequent difference Fourier maps. Their coordinates
were restrained in idealized positions, by means of AFIX43 or
AFIX 137 (for methyl groups) instructions, and their isotropic
displacement parameters constrained to 1.5 times the Ueq of the
corresponding bonded atom. At convergence, however, the re-
siduals were still rather high (R1¼0.135, wR2¼0.427) and six
Supplementary data
Supplementary data (Spectroscopic data, copies of the 1H and 13
C
NMR spectra for all compounds; crystallographic materials, fluo-
rescence measurements for compounds 8d and 21d.) related to this
article can be found at http://dx.doi.org/10.1016/j.tet.2015.05.046.
References and notes
1. (a) Dell’Erba, C.; Spinelli, D.; Leandri, G. J. Chem. Soc., Chem. Commun. 1969, 549;
(b) Dell’Erba, C.; Mele, A.; Novi, M.; Petrillo, G.; Stagnaro, P. Tetrahedron Lett.
1990, 31, 4933e4936; (c) Dell’Erba, C.; Mele, A.; Novi, M.; Petrillo, G.; Stagnaro,
P. Tetrahedron 1992, 48, 4407e4418; (d) Guanti, G.; Dell’Erba, C.; Leandri, G.;
Thea, S. J. Chem. Soc., Perkin Trans. 1 1974, 2357e2360; (e) Surange, S. S.; Ku-
maran, G.; Rajappa, S.; Rajalakshmi, K.; Pattabhi, V. Tetrahedron 1997, 53,
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Cosimelli, B.; Spinelli, D. Tetrahedron 2001, 57, 8159e8165.
additional peaks of non-negligible electron density, with values
ꢁꢂ3
ranging between 6.6 andw1.0 eA , appeared in the
DF map. All
residual peaks were located across the b edge of the cell, at co-
ordinates xz0.0, yz0.5, zz0.0, namely approximately around
a centre of symmetry. After some unfruitful attempts to fit the
observed peaks according to the solvent molecule (AcOEt), also
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the structure solution in the acentric space group P1, the presence
of disordered solvent molecules has been regarded as the only
plausible explanation.
2. For reviews see: (a) Bianchi, L.; Maccagno, M.; Petrillo, G.; Sancassan, F.;
Spinelli, D.; Tavani, C. In Targets in Heterocyclic Systems: Chemistry and Proper-
ꢀ
ties; Attanasi, O. A., Spinelli, D., Eds.; Societa Chimica Italiana: Rome, Italy,
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E.; Sancassan, F.; Severi, E.; Spinelli, D.; Tavani, C.; Viale, M. In Targets in Het-
erocyclic Systems: Chemistry and Properties; Attanasi, O. A., Spinelli, D., Eds.;
ꢀ
Societa Chimica Italiana: Rome, Italy, 2007; Vol. 11, pp 1e20; 2008; (c) Bianchi,
In order to improve the structural model, the BYPASS procedure
was applied,25 using the SQUEEZE routine as implemented in the
PLATON program.26 According to this procedure, the diffuse elec-
tron density in the disordered areas is calculated and referred back,
by means of discrete Fourier transform, to the observed structure
factors; the corrected data, obtained by subtracting the contribu-
tion of the disordered solvent, are then used in the subsequent
refinement of the ordered part of the structure. In the present case,
the total volume of the potential solvent area in the unit cell is
L.; Dell’Erba, C.; Maccagno, M.; Morganti, S.; Petrillo, G.; Rizzato, E.; Sancassan,
F.; Severi, E.; Spinelli, D.; Tavani, C. Arkivoc 2006, vii, 169e185 For biologically
active compounds see: (d) Fontana, A.; Viale, M.; Guernelli, S.; Gasbarri, C.;
Rizzato, E.; Maccagno, M.; Petrillo, G.; Aiello, C.; Ferrini, S.; Spinelli, D. Org.
Biomol. Chem. 2010, 8, 5674e5681; (e) Viale, M.; Petrillo, G.; Maccagno, M.;
ꢀ
Castagnola, P.; Aiello, C.; Cordazzo, C.; Mariggio, M. A.; Jadhav, S. A.; Bianchi, L.;
Leto, G.; Rizzato, E.; Poggi, A.; Spinelli, D. Eur. J. Pharmacol. 2008, 588, 47e51; (f)
ꢀ
Petrillo, G.; Mariggio, M. A.; Aiello, C.; Cordazzo, C.; Fenoglio, C.; Morganti, S.;
Croce, M.; Rizzato, E.; Spinelli, D.; Maccagno, M.; Bianchi, L.; Prevosto, C.; Ta-
vani, C.; Viale, M. Bioorg. Med. Chem. 2008, 16, 240e247; (g) Petrillo, G.; Fe-
ꢀ
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3
ꢁ
185 A , corresponding to a total electron count of 43. These values
are compatible with the presence of 1 molecule of ethyl acetate per
3
ꢁ
unit cell (VAcOEt: 88 A ; electrons per molecule: 48), i.e., a host:-
guest ratio ofw2:1.
The final indexes are: R1¼0.048 (over 3920 reflections with
Fo>4
s
Fo) and wR2¼0.138 for 246 refined parameters and 5383
reflections, max shift/e.s.d¼0.014, Goodness of fit S¼1.049,
ꢁꢂ3 ꢁꢂ3
Drmin¼ꢂ0.31 eA Drmax¼þ0.28 eA
,
.
Fig. 1 shows the ortep diagram of the molecule with atom
numbering. Bond distances and bond angles compare well with
tabulated values and only one slightly short intermolecular contact,
involving the terminal C17 methyl group, has been found. The
.
molecules are linked through intermolecular N9eH9
.O2 hy-
drogen bonds (as plotted in Supplementary data, Fig. 2) [O2 in (ꢂx,
ꢁ
ꢂy, ꢂz), donoreacceptor distance d¼2.903(3) A and N9eH9eO2
angle of 159.3(1)ꢀ], giving rise to pairs, which are located at the
origin of the elementary cell. As an example, the packing of the
molecules is viewed in the projection along the [100] direction,
where the shaded areas corresponding to the voids accessible to
the disordered solvent, are also highlighted (Supplementary data,
Fig. 3).
4. Harshadas, M. M.; Dachepally, A. K.; Bandi, C. R. Helv. Chim. Acta 2009, 92,
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€
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Data centre as supplementary publication numbers CCDC-1026522.
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€
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€
ꢂ
ꢂ
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