Regioselective electrophilic access to naphtho[1,2- b:8,7- b ′]- and -[1,2- b:5,6- b ′]dithiophenes

Article abstract of DOI:10.1021/jo400205j

A two-step one purification access to dichloronaphtho[1,2-b:8,7-b′] and [1,2-b:5,6-b′]dithiophenes using bis-alkylnaphthyl alkynes and phthalimidesulfenyl chloride as starting materials has been developed. The functionalization of the carbon-chlorine bonds allowed further modification of NDT core, broadening the potential of the methodology.

Full text of DOI:10.1021/jo400205j

Note
pubs.acs.org/joc
Regioselective Electrophilic Access to Naphtho[1,2‑b:8,7‑b′]- and
-[1,2‑b:5,6‑b′]dithiophenes
Caterina Viglianisi,* Lucia Becucci, Cristina Faggi, Sara Piantini, Piero Procacci, and Stefano Menichetti*
̀
Dipartimento di Chimica ‘Ugo Schiff’, Universita di Firenze, Via della Lastruccia 3-13, I-50019 Sesto Fiorentino, Italy
S
* Supporting Information
ABSTRACT: A two-step one purification access to
dichloronaphtho[1,2-b:8,7-b′] and [1,2-b:5,6-b′]dithiophenes
using bis-alkylnaphthyl alkynes and phthalimidesulfenyl chloride
as starting materials has been developed. The functionalization of
the carbon−chlorine bonds allowed further modification of NDT
core, broadening the potential of the methodology.
ompounds containing the benzo[b]thiophene nucleus
the cyclization.9,11 All these methods require the preventive
regioselective bis-functionalization of an aromatic skeleton,
generally not a trivial task above all when two thiophene units
have to be assembled. Several years ago, we reported an easy
synthesis of 3-chlorobenzo[b]thiophenes exploiting the reac-
tivity of the phthalimidesulfenyl chloride (PhtNSCl, Pht =
phthaloyl, 5).12 As described in Scheme 1, the procedure takes
C
have found a huge number of applications in medicinal
chemistry as well as, more recently, in material science. For
example, raloxifene (1) (Figure 1) is a marketed drug used for
Scheme 1. Synthesis of Benzo[b]thiophenes from
Monoalkylarylalkynes via Electrophilic Addition and
Internal Electrophilic Aromatic Substitution
Figure 1. Raloxifene (1) and model naphthodithiophenes (NDTs) 2−
4.
osteoporosis and estrogen-related cancers;1 several raloxifene
analogues show a similar selective estrogen receptor modulator
(SERM) activity,2 and many other compounds containing the
benzo[b]thiophene skeleton display a broad range of
pharmacological effects.3−7 On the other hand, thiophene and
benzothiophene derivatives have recently found application in
material science for the preparation of OLED and OFET.8
Among these systems, polycondensed heteroaromatics like
naphthodithiophenes (NDTs) 2−4 (Figure 1) are commonly
indicated as useful cores for electronic organic devices yet
scarcely studied mainly due to the difficulties of preparation.9
Hence, any new approach to the synthesis of the
benzothiophene moiety represents an important achievement,
and particularly appealing are those methods that allow the easy
regioselective fusion of the five-membered ring to a
polycondensed aromatic. Several modern and elegant methods
foresee the cyclization of 1-thio-2-unsuturated substituted
aromatics using stoichiometric or catalytic amounts of a proper
promoter.10
advantage of the high stereo- and regioselective electrophilic
addition of 5 to alkylaryl(or diaryl)alkynes that allowed the
preparation of (E)-1-chloro-1-aryl-2-N-thiophthalimides 6.12,13
These very stable crystalline sulfenamides can be cyclized to
3-chlorobenzo[b]thiophenes using a Lewis acid that, probably
interacting with the phthalimide nitrogen (vide infra), enhances
the electrophilic character of the sulfenic sulfur allowing an
intramolecular electrophilic substitution (iSEAr). The proce-
dure has been recently optimized, demonstrating its applic-
ability on solid phase and its utility for the preparation of
raloxifene analogues using, as an additional final step, the 3-
chloro-substituted carbon of benzo[b]thiophene as a supple-
mentary functionalization opportunity in Suzuki−Miyaura (S−
Interestingly, in some examples the sulfur atom is directly
inserted on the ortho-disubstituted aromatic while promoting
Received: January 31, 2013
© XXXX American Chemical Society
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M) or other Pd-catalyzed cross-coupling reactions (Scheme
1).14
Actually, a detailed examination of the 1H NMR of the crude
obtained after the reaction of 5 with 7 showed the formation of
tiny amounts of naphthodithiophene 12 directly during the
electrophilic addition step. We speculate that, as it occurred in
the related iSEAr of o-diarylamino-N-thiophthalimides leading
to [1,4]benzothiazine heterocyles,15 HCl, reasonably formed
during the addition process by reaction of sulfenyl chloride 5
with adventitious traces of water, could also operate as
promoter of the iSEAr process. In order to verify this
hypothesis, we kept N-thiophthalimide 11 in dry DCM
previously saturated with gaseous HCl, and indeed, we could
observe the formation of reasonable amounts of 12 without,
however, achieving the complete consumption of the starting
material. Enduring to study the ability of protic acids in
promoting the iSEAr, eventually we were able to isolate quite
good yield of 12 (65%) reacting crude 11 with 4 equiv of triflic
acid in dichloroethane (DCE) at 60 °C (Scheme 2).
Obviously, this methodology does not require an ortho-
functionalized aromatic system. Thus, it seems particularly
feasible for the preparation of polycondensed systems like
NDTs 2−4 using bis-alkylnaphthyl alkynes as starting materials.
These latter, in turn, can be easily prepared via a double-
Sonogashira cross-coupling method. Indeed, applying the
Sonogashira reaction to 2,7-, 2,6-, and 1,5-bis-naphtho-O-
triflates, we prepared and used bis-naphthoalkynes 7−10,
depicted in Figure 2, to verify the applicability of the above-
mentioned procedure for the preparation of NDT derivatives.
Additional information on the actual mechanism of this acid-
promoted (Lewis and/or protic) thiophene ring closure from
(E)-1-chloro-1-aryl-2-N-thiophthalimides was collected by
reacting 11 and AlCl3 in the presence of stoichiometric
amounts of 2,6-ditert-butylpyridine, a hindered base able to
trap protons but unable to coordinate AlCl3. Interestingly,
under these conditions, only trace amounts of 12 were
observed in the crude reaction mixture, suggesting that the
protonation of the sulfenamide nitrogen,16 more than the
interaction with the Lewis acid, is the real trigger event for the
cyclization. Thus, in this case,17 probably, protons are the real
promoters of the iSEAr, and AlCl3, or the other Lewis acids able
to provide the cyclization,12 serve just to generate protons in
the reaction mixture as it occurs in several other peculiar
examples recently reported by Spencer.18
The use of triflic acid as promoter, avoiding the formation of
the aluminum salts during the alkaline workup, further
simplifies the synthetic procedure, and we operated as depicted
in Scheme 2 to cyclize the crude N-thiophthalimides obtained
by addition of 5 to alkynes 8 and 9 (see the Experimental
Section). Under these conditions, bis-naphthodithiophenes 13
and 14 were isolated, from the corresponding crude N-
thiophthalimides as single regioisomers in 78% and 85% yields
respectively (Figure 3). On the other hand, the electrophilic
Figure 2. Bis-naphthoalkynes 7−10 used in this study.
Compound 7 was reacted with 5 in dry DCM at room
temperature for 12 h to give the expected bis-N-vinyl-
thiophthalimide 11 in quite good yield (Scheme 2). The
a
Scheme 2
a
Reagents and conditions: (a) 5, 2.2 equiv of DCM, rt, 12 h, 67%; (b)
AlCl3, 4 equiv, DCM, rt, 30 min, 48%; (c) TfOH, 4 equiv of DCE, 60
°C, 17 h, 65%.
crude was separated in two identical portions; the first was
purified by flash chromatography (67% yield of 11) and reacted
with AlCl3 in dry DCM while the second was reacted with
AlCl3 under the same conditions without any previous
purification. Satisfied, we verified the formation of 2,9-dibutyl-
3,8-dichloronaphtho[1,2-b:8,7-b′]dithiophenes (12) as a single
regioisomer isolated, in both experiments, in reasonable and
comparable yields (52% and 48%, respectively), indicating the
possibility to use this procedure to access to NDT systems also
avoiding the column chromatography purification of the
intermediate N-thiophthalimides (Scheme 2).
Figure 3. NDTs 13−15 and mixed thiophene/thiapyrene derivative
16 prepared in this study.
addition of 5 to 1,5-bis-alkyne 10 gave the worst results, and
the following cyclization, using either TfOH or AlCl3, afforded
moderate yields (42%) of an inseparable 1:1 mixture of NDT
15 and compound 16 containing a thiophene and a six-
membered thiapyrene ring (Figure 3).
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The results obtained show that the transformation of
alkylarylalkynes into 3-chlorobenzothiophene, mediated by
sulfenyl chloride 5, can be easily applied for the preparation
of NDT derivatives, in particular using 2,6- and 2,7-dialkynyl-
substituted naphthalenes as starting material.
The solid-state packaging of 12 is quite peculiar: the NDT
units are superimposed at 3.51 Å with an alternate little
deviation from the molecular axis that prevents a full eclipsing.
A columnar structure appears in the crystal with one alkyl
group completely out of the plane of the dithiophene skeleton.
Interestingly, the direction of the sulfur atoms (i.e., the
convexity of structure 12) is inverted in adjacent rows of
such a “columnar” network. On the other hand, compounds 14
and 15 are completely flat, all non-hydrogen atoms, including
all sp3 carbons, laying exactly on a plane, giving rise to a
tridimensional structure of parallel layers with a different
packaging motif at a distance of 3.52 and 3.56 Å, respectively.
In particular, in the solid state, NDT 14 shows a network of
short contacts (2.77 Å) between a hydrogen of the CH2 linked
to the 2-thienyl position and the π-electronic density in the
average plane of molecules of the upper and lower layers (see
Figure SI_06 in the Supporting Information).
Worthy of mention is the possibility to easily isolate the quite
uncommon [1,2-b:8,7-b′]dithiophene derivatives like 12 and
13, the former testifying how the proposed procedure is also
perfectly tolerated by the primary bromide group. Compounds
12−14 were isolated as single regioisomers as expected due to
the high nucleophilicity of the α-position of the naphthalene
ring. Indeed, in the case of N-thiophthalimide obtained by
addition of sulfenyl chloride 5 to 1,5-bis-substituted alkynyl-
naphthalene 10, the high reactivity of α position induces a
certain amount of “1 to 8” ring closure (roughly 1/4 of the
cyclization processes) leading to the formation of derivative 16
containing a thiophene and a thiapyrene ring system. At the
same time, the high reactivity of the naphthalene α-position
does not allow the use of the present method to prepare
compound 2 (Figure 1) and its syn-isomer, naphtho[2,3-b:7,6-
b′]dithiophene.
Density functional calculations (Experimental Section) were
employed to compute the optimized geometry for each of the
compounds 12, 14, 17, and 18 in the gas phase. Expectedly, for
all molecules, the HOMO−LUMO orbitals are systematically
delocalized on the extended planar aromatic system. HOMO−
LUMO energy gaps, reported in Table 1, appear slightly
The above procedure leads to the formation of 3-chloro-2-
alkyl-substituted naphthothiophenes. Although α-unsubstituted
NDTs are the most useful materials for further application to
materials science and “naked” NDTs cannot be prepared with
this method, the presence of the chlorine atom, instead of being
a drawback, can be exploited as an additional synthetic option.
In fact, the carbon−chlorine bond allows the functionalization
of the heteroaromatic ring via cross-coupling reactions.14 For
example, DBTs 12 and 14 were reacted with p-methoxyboronic
acid using PEPSSI-i-Pr as catalyst under S−M cross-coupling
conditions to give bis-aryl derivatives 17 and 18 in 66%19 and
89% yield, respectively, as reported in Scheme 3.
a
Table 1. HOMO and LUMO Energies for NDTs 12, 14, 17,
and 18
NDT
HOMO (eV)
LUMO (eV)
ΔE (eV)
12
14
17
18
−5.76038
−5.61752
−5.05207
−5.13778
−1.18451
−1.32737
−0.89634
−0.91403
4.57587
4.29015
4.15572
4.22375
a
Calculated at DFT B3LYP-6-31G* level.
a
Scheme 3
sensitive either to the shape of the NDT skeleton or to the
substituent on C3 (i.e., a chlorine or a p-methoxybenzene).
Interestingly, in compounds 17 and 18, the additional aromatic
substituents on C3 appear to contribute only marginally to the
HOMO−LUMO orbitals and, correspondingly, to the
narrowing of the energy gap. In these compounds, the p-
methoxybenzene moieties are in a tilted, quasi-T-shaped
configuration with respect to the NTD skeleton, an effect
very likely due to steric hindrance, that is maintained in the
crystal phase (HOMO−LUMO orbitals and ORTEP diagrams
of 12, 14, 17, and 18 are available as Supporting Information).
The computed band gaps listed in Table 1, confirmed by
UV−vis spectra (see the Supporting Information), are in
agreement with those reported for similar structures9 and
indicate that after suitable structural transformations, such as
polymerization or introduction of push−pull termini, the
NDTs prepared in this study can reach the HOMO−LUMO
gaps required for application in organic electronic devices.
In summary, a simple access to NDT systems, including
uncommon naphtho[1,2-b:8,7-b′]dithiophenes, has been
achieved using easily available bis-alkylarylalkynes and sulfenyl
chloride 5 as starting materials. The procedure foresees two
electrophilic processes and required a single purification. The
possibility to use the carbon−chlorine bond to further
functionalize the NDT core enlarges the scope of this
methodology for the preparation of polyconjugated hetero-
acenes with applications in organic electronic devices.
a
Reagents and conditions: (a) p-methoxyphenylboric acid (3 equiv),
K2CO3 (2 equiv), PEPSSI-iPr (0.1 equiv), toluene, 100 °C, 17−40 h.
This reaction is of particular interest considering that metal-
catalyzed cross-coupling processes are often used as the method
of choice for the functionalization or the polymerization steps
required for transforming thiophene-containing derivatives into
materials useful for electronic organic devices. Hence, the
procedure described in this paper offers an easy way to obtain
NDT derivatives, like 12−14, prearmed for a cross-coupling-
based structural modification.
Polycondensed systems 12−18 were fully characterized, and
in the case of NDTs 12, 14, 15,20 17, and 18, suitable crystals
for X-ray analysis were obtained, confirming structural
attributions.
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mmol) in THF dry (1.6 mL) were added to the suspension at rt, and
the mixture was stirred at 100 °C for 19 h. The mixture was then
diluted with petroleum ether (100 mL) and the organic phase washed
with saturated NH4Cl (1 × 100 mL) and water (2 × 100 mL). The
organic phase was dried over Na2SO4, filtered, and evaporated under
vacuum to give a brown oil (270 mg). The crude was purified by flash
chromatography on silica gel (eluent: DCM/petroleum ether = 1/5)
to give bis-alkyne 7 as a colorless oil (120 mg; 96% yield). 1H NMR δ:
7.81 (s, 2H); 7.68 (d, J = 8.8 Hz, 2H); 7.41 (dd, J = 8.8 and 1.6 Hz;
2H); 2.46 (t, J = 6.8 Hz, 4H); 1.74−1.41 (m, 8H); 0.97 (t, J = 6.8 Hz,
6H) ppm. 13C NMR δ: 132.7; 131.4; 130.5; 129.1; 127.5; 122.0; 91.2;
80.7; 30.8; 22.1; 19.2; 13.6 ppm. IR ν: 3064 (C−H st aromatic); 2963
+ 2932 (C−H st aliphatic); 2240 (CC st) cm−1. Anal. Calcd for
C22H24: C, 91.61; H, 8.39. Found: C, 91.23; H, 8.51
2,7-Bis(4-bromobut-1-yn-1-yl)naphthalene (8). Following the
general procedure the crude was purified by flash chromatography
on silica gel (eluent: DCM/petroleum ether = 4/1) to give bis-alkyne
8 as a colorless oil (140 mg, 37%). 1H NMR δ: 7.85 (s, 2H); 7.71 (d, J
= 8.4 Hz, 2H); 7.45 (dd, J = 8.4 and 1.4 Hz; 2H); 3.56 (t, J = 7.2 Hz,
4H); 3.03 (t, J = 7.2 Hz, 4H) ppm. 13C NMR δ: 132.5; 131.9; 131.0 ;
129.2; 127.8; 121.2; 87.4; 82.5;29.5; 24.0 ppm. IR ν: 3066 (C−H st
aromatic); 2972 + 2925 (C−H st aliphatic); 2247 (CC st) cm−1.
Anal. Calcd for C22H14Br2: C, 55.42; H, 3.62. Found: C, 55.55; H,
3.27.
2,6-Di(hex-1-yn-1-yl)naphthalene (9). Following the general
procedure, the crude was purified by flash chromatography on silica
gel (eluent: DCM/petroleum ether = 1/3) to give 9 as a pale yellow
solid (200 mg, 57% yield).Mp: 77−78 °C. 1H NMR δ: 7.86 (as, 2H);
7.68 (d, J = 8.4 Hz, 2H); 7.45 (dd, J = 8.4 and 1.6 Hz; 2H); 2.47 (t, J =
7.2 Hz, 4H); 1.68−1.60 (m, 4H); 1.58−1.48 (m, 4H); 1.01 (t, J = 7.2
Hz, 6H) ppm. 13C NMR δ: 132.1; 130.7; 129.3; 127.4; 121.8; 91.3;
80.8; 30.9; 22.1; 19.2; 13.6 ppm. IR ν: 3060 (C−H st aromatic); 2965
+ 2931 (C−H st aliphatic); 2241 (CC st) cm−1. Anal. Calcd for
C22H24: C, 91.61; H, 8.39. Found: C, 91.41; H, 8.44.
1,5-Di(hex-1-yn-1-yl)naphthalene (10). Following the general
procedure the crude is purified by flash chromatography on silica gel
(eluent: DCM/petroleum ether = 1/5) to give bis-alkyne 10 as a
yellow solid (265 mg, 83%). Mp: 54−55 °C. 1H NMR δ: 8.31 (dd, J =
8.2 and 0.8 Hz, 2H); 7.65 (dd, J = 7.0 and 0.8 Hz, 2H); 7.47 (dd, J =
8.2 and 7.0 Hz, 2H); 2.58 (t, J = 7.0 Hz, 4H); 1.74−1.67 (m, 4H);
1.62−1.53 (m, 4H); 1.01 (t, J = 7.0 Hz, 6H) ppm. 13C NMR δ: 133.4;
130.4; 126.2; 125.7; 122.1; 95.7; 78.5; 30.9; 22.1; 19.4; 13.6 ppm. IR ν:
3056 (C−H st aromatic); 2961 + 2926 + 2875 (C−H st aliphatic);
2245 (CC st) cm−1. Anal. Calcd for C22H24: C, 91.61; H, 8.39.
Found: C, 91.77; H, 8.19.
EXPERIMENTAL SECTION
■
General Experimental Methods. Commercially available re-
agents, catalysts, and ligands were used as obtained, unless otherwise
stated, from freshly opened containers without further purifications.
Toluene was distilled from sodium, THF was distilled from sodium in
the presence of the blue color of benzophenone kethyl, and DCM and
dichloroethane (DCE) were distilled from CaCl2. All of the reactions
are monitored by TLC on commercially available precoated plates
(silica gel 60 F 254), and the products were visualized with acidic
vanillin solution. Silica gel 60, 230−400 mesh, is used for column
chromatography. Melting points are uncorrected. H and 13C NMR
1
spectra were recorded, unless otherwise noted, in CDCl3 at 400 and
100 MHz using residual CHCl3 at 7.26 ppm and CDCl3 at 77.00 ppm
as reference lines, respectively. FTIR spectra are recorded in CDCl3
solutions. UV−vis spectra are recorded in dry DCM using 10−4
M
solutions. Cyclic voltammograms were obtained on a platinum
working electrode by scanning the applied potential between −0.45
and +1.250 V vs the Fc+/0 couple, at a scan rate of 200 mVs−1, in a
DCM solution of 0.2 M tetrabutylammonium hexafluorophosphate
and 5 × 10−4 M of the different NDTs. Ab initio calculations.
Hydrogen atoms were added to the coordinates of the heavy atoms
(taken from the raw crystallographic data) by means of the program
ORAC.21 These starting coordinates underwent a molecular-
mechanics minimization using the AMBER/GAFF force field.22 On
the resulting coordinates, a full ab initio geometry optimization was
performed at the Hartree−Fock level of theory using a 4-31G basis set.
The last configuration, optimized at the HF/4-31G level, underwent a
further geometry refinement through a constrained optimization using
density functional theory (DFT) with the B3-LYP exchange-
correlation functional23,24 and the split-valence polarized basis-set 6-
31G(d). The DFT-constrained optimization involved only the atoms
belonging to the extended NTD aromatic system including (in 17 and
18) the p-methoxybenzene substituents (alkyl groups were kept
frozen). The HOMO−LUMO energy gap was computed using the
eigenvalues of the last optimized configuration at the B3-LYP/6-
31G(d) level of theory. All ab initio calculations were done with the
program Gaussian09. The HOMO and LUMO orbitals surfaces for the
resulting minimized structures were produced using the cross-platform
molecule editor Avogadro.25 X-ray. Measurements and X-ray analysis
were carried out at 100 K for compounds 12 and 14 and at 120 K for
compounds 15, 17, and 18. Cu/Kα radiation (40 mA/−40 kV),
monochromated was used for cell parameter determination and data
collection. The integrated intensities, measured using the ω scan
mode, were corrected for Lorentz and polarization effects.26 Direct
methods of SIR200427 were used in solving the structures, and they
were refined using the full-matrix least-squares on F2 provided by
SHELXL97.28 A multiscan symmetry-related measurement was used as
the experimental absorption correction type. Hydrogen atoms were all
assigned in calculated positions for compounds 12, 15, and 18,
whereas for compounds 14 and 17 they were found, when possible, in
the Fourier difference map. The non-hydrogen atoms were refined
anisotropically; hydrogen atoms were refined as isotropic. The X-ray
CIF files are available as Supporting Information and have been
deposited at the Cambridge Crystallographic Data Centre and
allocated with the deposition numbers CCDC 912636 (compound
12), CCDC 912635 (compound 14), CCDC 912638 (compound 15),
CCDC 912637(compound 17) and CCDC 912639 (compound 18).
Copies of the data can be obtained, free of charge, from CCDC, 12
Union Road, Cambridge, CB2 1EZ UK (e-mail: deposit@ccdc.cam.ac.
uk; Internet://www.ccdc.cam.ac.uk).
The addition of phthalimidesulfenyl chloride 5 to alkynes 7−10 was
carried out following previously reported procedures.12,14 The
preparation of N-thiophthalimide 11 is described as an example of
the general protocol. N-Thiophthalimides obtained reacting 5 with
alkynes 8−10 were similarly obtained and used after workup without
further purifications.
N-Thiophthalimide (11). To a solution of alkyne 7 (293 mg, 1.02
mmol) in dry DCM (10 mL) was added dropwise a solution of
sulfenyl chloride 5 (485 mg, 2.23 mmol) in dry DCM (22 mL) at −10
°C under nitrogen during 1 h. The mixture was stirred at rt for 12 h
and then diluted with DCM (30 mL) and washed with water (2 × 30
mL). The organic phase was dried over Na2SO4, filtered, and
evaporated under vacuum to give a brownish solid (780 mg). Half of
this crude (390 mg) was purified by flash chromatography on silica gel
(eluent: DCM/petroleum ether = 2/1) to give N-thiophthalimide
1
(11) as a white solid (140 mg, 67%). Mp: 151−152 °C. H NMR δ:
Synthesis. Bis-alkynes 7−10 were prepared from the correspond-
ing 2,7-, 2,6, and 1,5-bis-O-triflates using standard Sonogashira cross
coupling conditions. The preparation of 7 is reported as an example of
the general procedure.
2,7-Di(hex-1-yn-1-yl)naphthalene (7). In a Schlenk tube under
nitrogen, naphthalene-2,7-diyl-bis(trifluoromethansulfonate) (200 mg;
0.47 mmol), CuI (12 mg; 0.06 mmol) ,and Pd(PPh3)2Cl2 (46 mg; 0.07
mmol) were suspended in dry DMF (1.6 mL). N,N-Diisopropylethyl-
amine (364 mg; 2.82 mmol) and a solution of 1-hexyne (115 mg; 1.41
7.90 (as, 2H); 7.83−7.77 (m, 4H); 7.74−7.67 (m, 6H); 7.65 (dd, J =
8.4 and 1.6 Hz, 2H); 2.44 (t, J = 8.4 Hz, 4H); 1.80−1.72 (m, 4H);
1.45−1.36 (m, 4H); 0.93 (t, J = 8.4 Hz, 6H) ppm. 13C NMR δ: 167.4;
135.6; 134.8; 134.6; 132.8; 131.8; 131.6; 129.6; 128.4; 127.9; 127.3;
123.8; 32.1; 29.6; 22.5; 13.8 ppm. IR ν: 2965 (C−H st aliphatic); 1784
+
1741 + 1711 (CO st Pht) cm−1. Anal. Calcd for
C38H32Cl2N2O4S2: C, 63.77; N, 3.91; H, 4.51. Found: C, 63.63; N,
4.00; H, 4.77.
D
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Cyclization of crude N-thiophthalimides to the corresponding
NDTs was carried out using CF3SO3H or (and) AlCl3. Both
experimental conditions are reported for the preparation of derivative
12. The procedure with triflic acid is the general protocol used to
obtain the other NDTs.
2,9-Dibutyl-3,8-dichloronaphtho[1,2-b:8,7-b′]dithiophene (12).
(a). With AlCl3. To a solution of 11 (309 mg; 0.43 mmol) in dry
DCM (20 mL) kept under nitrogen was added AlCl3 (230 mg; 1.73
mmol) in small portions. A dark violet suspension was formed
immediately. The mixture was stirred for 30 min at rt and diluted with
DCM (30 mL), and the organic phase was washed with 1 M NaOH (3
× 30 mL) and water (4 × 30 mL). The organic phase was dried over
Na2SO4, filtered, and evaporated under vacuum to give a crude (150
mg) purified by flash chromatography on silica gel (eluent: petroleum
ether) to give NDT 12 as a white solid (94 mg, 52%).
1H NMR δ: 9.54 (d, J = 9.0 Hz, 2H, 15), 9.20 (dd, J = 8.0 and 1.2 Hz,
1H, 16), 7.90 (d, J = 9.0 Hz, 2H, 15), 7.72 (dd, J = 7.5 and 1.2 Hz, 1H,
16), 7.45 (dd, J = 8.0 and 7.5 Hz, 1H, 16), 7.33 (s, 1H, 16), 3.05 (t, J =
7.5 Hz, 4H, 15), 2.94 (t, J = 7.5 Hz, 2H, 16), 2.54 (t, J = 7.8 Hz, 2H,
16), 1.82−1.44 (m, 16H 15 + 16), 1.03−0.83 (m, 12H 15 + 16) ppm.
13C NMR δ: 139.6; 131.8; 127.6; 127.2; 122.2; 121.1; 120.3; 1198;
113.1; 34.8; 32.3; 32.2; 29.8; 28.5; 28.3; 22.4; 22.3; 22.2; 13.8; 13.7
ppm. Anal. Calcd for C22H22Cl2S2 (on the mixture): C, 62.70; H, 5.26.
Found: C, 62.28; H, 5.04. A slow evaporation of a DCM solution of a
1:1 mixture of 15 and 16 allowed the manual selection of colorless
plate of pure NDT 15, suitable for X-ray analysis, formed over a dark
yellow gummy oil still containing both derivatives. X-ray: triclinic,
space group P-1, a = 5.291(1) Å, b = 7.714(1) Å, c = 12.239(1) Å, α =
99.618(7)°, β = 94.426(7)°, γ = 102.384(8)°, V = 477.7(1) Å3, Z = 2,
Dc = 1.465, μ = 5.110 mm−1, F(000) = 220. 3252 reflections were
collected with a 5.98 < θ < 70.34 range with a completeness to θ
93.8%; 1722 were unique, the parameters were 118 and the final R
index was 0.0406 for reflections having I > 2σI and 0.0573 for all data.
Also in this case only a half molecule is contained in the asymmetric
unit for the same reason as for compound 14.
(b). With CF3SO3. A vial containing a solution of 11 (150 mg; 0.21
mmol) and CF3SO3H (126 mg; 0.84 mmol) in DCE (23 mL) was
stirred at 60 °C for 17 h. The mixture was diluted with DCM (20 mL)
and the organic phase washed with saturated Na2CO3 (2 × 30 mL)
and water (4 × 30 mL). The organic phase was dried over Na2SO4,
filtered, and evaporated under vacuum to give a brown solid (80 mg)
that was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give 12 as white solid (58 mg, 65%). Mp: 91−92
2,9-Dibutyl-3,8-bis(4-methoxyphenyl)naphtho[1,2-b;8,7-b′]-
dithiophene (17). In a Schlenk tube under nitrogen to a mixture of p-
methoxyphenylboronic acid (51 mg; 0.34 mmol), dry K2CO3 (94 mg;
0.68 mmol), and PEPPSI-i-Pr (3 mg; 0.04 mmol) was added a solution
of NDT 12 (48 mg; 0.11 mmol) in dry toluene (1.5 mL). The mixture
was stirred at 100 °C under an inert atmosphere for 17 h. The mixture
was then diluted with diethyl ether (40 mL) and the organic phase
washed with brine (3 × 30 mL). The organic phase was dried over
Na2SO4, filtered, and evaporated under vacuum to give a brown oil
(130 mg). The crude was purified by flash chromatography on silica
gel (eluent: DCM/petroleum ether = 1/4) to give derivative 17 as a
white solid (42 mg, 66%) along with the monoarylated derivative
1
°C. H NMR δ: 7.92 (d, J = 8.6 Hz, 2H); 7.86 (d, J = 8.6 Hz, 2H);
3.09 (t, J = 7.6 Hz, 4H); 1.88−1.81 (m, 4H); 1.56−1.47 (m, 4H); 1.02
(t, J = 7.6 Hz, 6H) ppm. 13C NMR δ: 139.7; 135.0; 130.4; 129.5;
126.3; 123.5; 119.3; 118.7; 32.7; 28.2; 22.3; 13.8 ppm. MS m/z (int
rel) 420 (56 M•+): 377 (100); 336 (54). Anal. Calcd for C22H22Cl2S2:
C, 62.70; H, 5.26. Found: C, 62.62; H, 5.01. X-ray: orthorhombic,
space group Pcca, a = 22.857(1) Å, b = 7.330(1) Å, c = 23.337(1) Å, V
= 3909.9(6) Å3, Z = 8, Dc = 1.432, μ = 4.995 mm−1, F(000) = 1760.
11144 reflections were collected with a 4.25 < θ < 71.53 range with a
completeness to θ 96.0%; 3661 were unique, the parameters were 236
and the final R index was 0.0565 for reflections having I > 2σI and
0.0753 for all data. No significant intra- or intermolecular interactions,
such as H-bonds or π-stacking between aromatic rings, were detected.
2,9-Bis(2-bromoethyl)-3,8-dichloronaphtho[1,2-b:8,7-b′]-
dithiophene (13). The crude obtained following the general procedure
is purified by flash chromatography on silica gel (eluent: petroleum
eter/DCM = 1/1) to give the NDT 13 as a brown solid (61 mg, 78%
yield). Mp: 154−155 °C. 1H NMR (400 MHz, CDCl3) δ: 7.95 (d, J =
9.0 Hz, 2H); 7.90 (d, J = 9.0 Hz, 2H); 3.74 (t, J = 6.0 Hz, 4H); 3.64 (t,
J = 6.0 Hz, 4H) ppm. 13C NMR (100 MHz, CDCl3) δ: 134.9; 134.8;
130.9; 130.1; 126.7; 12.3; 120.5; 119.8; 31.8; 30.2 ppm. MS m/z (int
rel %) 526/524/522/520 (35/81/76/28, M•+); 431/429/427 (50/
100/51); 347/349 (30). Anal. Calcd for C18H12Br2Cl2S2: C, 41.33; H,
2.31. Found: C, 41.11; H, 2.16.
1
mono-17 (white solid, 7 mg, 11%). Mp: 89−90 °C. H NMR δ: 7.83
(d, J = 8.4 Hz, 2H); 7.60 (d, J = 8.4 Hz, 2H); 7.38 (dd, J = 6.4 and 2.0
Hz, 4H); 7.07 (dd,, J = 6.4 and 2.0 Hz, 4H); 3.92 (s, 6H); 3.02 (t, J =
7.2 Hz, 4H); 1.86−1.81 (m, 4H); 1.48−1.38 (m, 4H); 0.92 (t, J = 7.2
Hz, 6H) ppm. 13C NMR δ: 158.9; 149.1; 143.0; 138.3; 134.4; 132.1;
131.4; 128.7; 127.9; 125.4; 120.5; 113.9; 55.3; 34.3; 28.7; 22.4; 13.8
ppm. MS m/z (int rel) 564 (100 M•+); 521 (38); 464 (28). Anal.
Calcd for C36H36O2S2: C, 76.56; H, 6.42. Found: C, 76,44, H, 6.38. X-
ray: triclinic, space group P-1, a = 9.525(1) Å, b = 11.520(1) Å, c =
13.591(1) Å, α = 81.463(4)°, β = 87.681(5)°, γ = 84.909(5)°, V =
1468.4(2) Å3, Z = 2, Dc = 1.277, μ = 1.881 mm−1, F(000) = 600.
16531 reflections were collected with a 4.66 < θ < 72.16 range with a
completeness to theta 96.9%; 5625 were unique, the parameters were
473 and the final R index was 0.0464 for reflections having I > 2σ I and
0.0772 for all data. No significant intra or intermolecular interactions
were detected.
2,7-Dibutyl-1,6-dichloronaphtho[1,2-b;5,6-b′]dithiophene (14).
The crude obtained following the general procedure is purified by
flash chromatography on silica gel (eluent: petroleum ether/DCM =
4/1) to give NDT 14 as a white solid (81 mg, 85%). Mp: 127−128 °C.
1H NMR δ: 7.92 (d, J = 8.4 Hz, 2H); 7.82 (d, J = 8.4 Hz, 2H); 3.01 (t,
2,9-Dibutyl-3-chloro-8-(4-methoxyphenyl)naphtho[1,2-b:8,7-b′]-
1
dithiophene (mono-17). H NMR δ: 7.97 (d, J = 8.7 Hz, 1H); 7.91
(d, J = 8.4 Hz, 1H); 7.86 (d, J = 8.7 Hz, 1H); 7.63 (d, J = 8.4 Hz, 1H);
7.37 (d, J = 9.0 Hz, 2H); 7.07 (d, J = 9.0 Hz, 2H); 3.91 (s, 3H); 3.13
(t, J = 7.2 Hz, 2H); 3.01 (t, J = 7.2 Hz, 2H); 1.93−1.76 (m, 4H);
1.56−1.35 (m, 4H); 1.05 (t, J = 8.4 Hz, 3H); 0.92 (t, J = 7.2 Hz, 3H)
ppm. 13C NMR δ: 159.0; 143.3; 139.5; 138.7; 134.8; 134.4; 131.7;
131.4; 130.9; 129.2; 127.7; 126.3; 125.6; 123.9; 121.1; 118.8; 118.7;
114.0; 55.3; 34.3; 32.7; 28.7; 28.2; 22.4; 22.4; 13.8 ppm. MS m/z (int
rel) 492 (87, M•+); 449 (100); 203 (29). Anal. Calcd for
C29H29ClOS2: C, 70.63; H, 5.93. Found: C, 70.38; H, 6.01.
2,7-Dibutyl-1,6-bis(4-methoxyphenyl)naphtho[1,2-b;5,6-b′]-
dithiophene (18). In a Schlenk tube under nitrogen to a mixture of p-
methoxyphenylboronic acid (75 mg; 0. 49 mmol), dry K2CO3 (132
mg; 0.96 mmol), and PEPPSI-i-Pr (4 mg; 0.05 mmol) was added a
solution of NDT 14 (70 mg; 0.16 mmol) in dry toluene (2 mL). The
mixture was stirred at 100 °C under an inert atmosphere for 40 h. The
mixture was then diluted with diethyl ether (40 mL) and the organic
phase washed with brine (3 × 30 mL). The organic phase was dried
over Na2SO4, filtered, and evaporated under vacuum to give a brown
solid (130 mg). The crude was purified by flash chromatography on
silica gel (eluent: DCM/petroleum ether = 1/3) to give derivative 18
J = 7.6 Hz, 4H); 1.82−1.74 (m, 4H); 1.53−1.44 (m, 4H); 1.0 (t, J =
7.6 Hz, 6H) ppm. 13C NMR δ: 138.2; 134.9; 134.5; 125.7; 120.6;
120.5; 118.5; 32.6; 28.0; 22.3; 13.8 ppm. MS m/z (int rel %) 420 (56
M•+); 377 (100); 336 (54). Anal. Calcd for C22H22Cl2S2: C, 62.70; H,
5.26. Found: C, 62.58; H, 5.32. X-ray: triclinic, space group P-1, a =
6.946(1) Å, b = 7.720(1) Å, c = 9.057(1) Å, α = 90.861(6), β =
89.656(6), γ = 98.724(5)°, V = 479.9(1) Å3, Z = 2, Dc = 1.458, μ =
5.086 mm−1, F(000) = 220. 2478 reflections were collected with a 6.45
< θ < 61.76 range with a completeness to θ 96.6%; 1442 were unique,
the parameters were 154 and the final R index was 0.0273 for
reflections having I > 2σI and 0.0313 for all data. In the asymmetric
unit there is a half molecule; this is because the center of symmetry in
the molecule coincides with the inversion center (group P-1).
2,7-Dibutyl-1,6-dichloronaphtho[1,2-b;5,6-b′]dithiophene (15)
and 5,9-Dibutyl-4,10-dichlorobenzo[de]thieno[3,2-g]thiochromene
(16). The crude obtained following the general procedure was purified
by flash chromatography on silica gel (eluent: petroleum ether) to give
a 1:1 mixture of 15 and 16 as a pale yellow glassy solid (63 mg, 42%).
E
dx.doi.org/10.1021/jo400205j | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
as a white solid (80 mg, 89%). Mp: 171−172 °C. 1H NMR δ: 7.92 (d,
J = 8.4 Hz, 2H); 7.56 (d, J = 8.4 Hz, 2H); 7.36 (d, J = 8.7 Hz, 4H);
7.06 (d, J = 8.7 Hz, 4H); 3.91 (s, 6H); 2.91 (t, J = 7.2 Hz, 4H); 1.78−
1.67 (m, 4H); 1.42−1.18 (m, 4H); 0.86 (t, J = 7.2 Hz, 6H) ppm. 13C
NMR δ: 158.9; 141.1; 137.7; 136.2; 134.7; 131.2; 127.9; 125.7; 121.8;
120.8; 114.0; 55.3; 34.1; 25.6; 22.3; 13.8 ppm. MS m/z (int rel) 564
(100 M•+); 521 (43); 464 (28). Anal. Calcd for C36H36O2S2: C, 76.56;
H, 6.42. Found: C, 76,39, H, 6.63. X-ray: triclinic, space group P-1, a =
10.689(1) Å, b = 14.404(1) Å, c = 19.076(1) Å, α = 98.344(3)°, β =
90.870(3)°, γ = 91.061(3)°, V = 2905.0(4) Å3, Z = 2, Dc = 1.291, μ =
1.901 mm−1, F(000) = 1200. 23272 reflections were collected with a
4.14 < θ < 70.66 range with a completeness to θ 95.3%; 10632 were
unique, the parameters were 721 and the final R index was 0.0505 for
reflections having I > 2σI and 0.0757 for all data. The asymmetric unit
contains two independent molecules as they are not equivalent from a
crystallographic point of view. It is mainly due to the different torsion
angles between sulfur atoms and the alkylic chains. No significant
intra- or intermolecular interactions can be detected.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Copies of 1H and 13C NMR spectra of compounds 7−18; CIF
files and ORTEP diagrams of compounds 12, 14, 15, 17, and
18; UV−vis spectra and cyclic voltammograms of compounds
12−14, 17, and 18; HOMO−LUMO orbitals, atom
coordinates, and absolute energies of compounds 12, 14, 17,
and 18. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: caterina.viglianisi@unifi.it, stefano.menichetti@unifi.it.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Work carried out in the framework of MIUR PRIN2010-2011
project “PROxi” cod. 2010PFLRJR_007.
(10) (a) Yue, D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905−1909.
(b) Nakamura, I.; Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006,
45, 4473−4475. (c) Jeong, J. H.; Yoon, U. Y.; Jang, S. H.; Yoo, U.-A.;
Kim, S. N.; Truong, B. T.; Shin, S. C.; Yoon, Y.-J.; Singh, O. M.; Lee,
S.-G. Synlett 2007, 1407−1410. (d) Matsnev, A.; Noritake, S.;
Nomura, Y.; Tokunaga, E.; Nakamura, S.; Norio Shibata, N. Angew.
Chem., Int. Ed. 2010, 49, 572−576. (e) Jacubert, M.; Tikad, A.; Provot,
O.; Hamze, A.; Brion, J.-D.; Alami, M. Eur. J. Org. Chem. 2010, 4492−
4500.
DEDICATION
■
This paper is dedicated to the memory of Prof. Alessandro
Degl’Innocenti.
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