The influence of tetrahydroquinoline rings in dicyanomethylenedihydrofuran (DCDHF) single-molecule fluorophores

Article abstract of DOI:10.1016/j.tet.2006.10.044

We have synthesized several series of DCDHF fluorophores with the amine donor either acyclic or constrained in one or two tetrahydroquinoline rings. The absorption and the fluorescence emission wavelengths and quantum yields have been determined and correlated with the specific donor structures. Generally, inclusion of the donor in a ring annulated to the benzene or naphthalene aromatic (Ar) π-core results in a bathochromic shift of absorption and emission accompanied by an increase in the quantum yield. Thus, the tetrahydroquinoline donor provides an efficient way to tailor the properties of fluorophores with substituted amines as electron-donating groups.

Full text of DOI:10.1016/j.tet.2006.10.044

Tetrahedron 63 (2007) 103–114
The influence of tetrahydroquinoline rings in
dicyanomethylenedihydrofuran (DCDHF)
single-molecule fluorophores
Hui Wang,a Zhikuan Lu,a Samuel J. Lord,b Katherine A. Willets,b Jeffrey A. Bertke,a
Scott D. Bunge,a W. E. Moernerb and Robert J. Twiega,
*
aDepartment of Chemistry, Kent State University, Kent OH 44242, USA
bDepartment of Chemistry, Stanford University, Stanford, CA 94305-5080, USA
Received 28 August 2006; revised 13 October 2006; accepted 18 October 2006
Available online 13 November 2006
Abstract—We have synthesized several series of DCDHF fluorophores with the amine donor either acyclic or constrained in one or two
tetrahydroquinoline rings. The absorption and the fluorescence emission wavelengths and quantum yields have been determined and corre-
lated with the specific donor structures. Generally, inclusion of the donor in a ring annulated to the benzene or naphthalene aromatic (Ar)
p-core results in a bathochromic shift of absorption and emission accompanied by an increase in the quantum yield. Thus, the tetrahydro-
quinoline donor provides an efficient way to tailor the properties of fluorophores with substituted amines as electron-donating groups.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
tetrahydroquinoline group would be one way to shift the
absorption and emission to longer wavelengths.
Fluorescence is a physical property of many materials,
which has been exploited in a wide variety of applications.
As just one example, organic dyes are extensively employed
in biological systems as labels and tags to study the meta-
bolism and other fundamental processes. As a result, there
is much current interest in optimizing and tuning the per-
formance of fluorescent dyes for such purposes. In cells,
fluorescence detection sensitivity depends on reducing back-
ground signals, which arise from autofluorescence or from
unbound or nonspecifically bound fluorophores. Because
cells autofluorescence with short wavelength excitation,
one way to minimize background is to optimize fluorophores
for longer wavelength absorption and emission.1 At the same
time this longer wavelength can reduce the light scattering
by dense media such as tissues and improve penetration of
the excitation light. Finally, optimizing the Stokes shift
can result in a greater differentiation between the absorption
spectrum and the emission spectrum, which makes it easier
to use filters to block excitation light while still collecting
most of the emitted fluorescence. It is well-known that polar
fluorescent dyes containing an electron-donating group (an
amino group in most cases2–4) and an electron withdrawing
group often exhibit large Stokes shifts because of intramo-
lecular charge-transfer (ICT) states. In the case of an amine
donor, replacing the typical dialkylamino groups by a cyclic
Recently, we have focused on the design and synthesis of
a new structure class of donor–acceptor fluorophores, the
dicyanomethylenedihydrofuran (DCDHF) dyes.5–8 The
DCDHF fluorophores can be imaged at the single-molecule
level with additional beneficial properties such as a vis-
cosity-dependent fluorescence, strong solvatochromism,
significant ground-state dipole moment, and moderate
hyperpolarizability. One of the most important characteris-
tics of fluorophores for imaging applications is the fluores-
cence quantum yield (FF), a quantity, which should be as
large as possible. In our previous mechanistic studies, inter-
molecular twisting around the dicyanomethylene bond was
shown to strongly affect FF by introducing nonradiative
deexcitation pathways.9–11 Twisting about the amine–phenyl
bond might also have an effect on the brightness of the
emission. To test this idea, we synthesized several new
DCDHF fluorophores with a tetrahydroquinoline ring in an
attempt to improve the quantum yield and simultaneously
shift the wavelength further to the red.
2. Synthesis
The DCDHF dyes 7–9 that contain a single benzene ring and
a single alkene conjugated unit were examined first (Scheme
1). These dyes follow the same synthetic protocol12 as was
used for electro-optical chromophores containing this
* Corresponding author. Tel.: +1 330 672 2791; fax: +1 330 672 3816;
e-mail: rtwieg@lci.kent.edu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.044

104
H. Wang et al. / Tetrahedron 63 (2007) 103–114
O
H
O
DMF POCl3
1-bromohexane
DMF POCl3
HN
N
N
N
N
DMF K2CO3
H
5
5
4
5
6
NC
O
H
NC
NC
NC
CN
CN
CN
N
O
CN
Me
Me
O
CN
CN
CN
N
+
OH
O
Me
CN
1
2
3
7
NC
O
O
N
H
5
5
N
5
8
NC
O
O
N
H
4
N
9
Scheme 1.
DCDHF acceptor group.13–17 The precursor 3 was made by
condensation of a-hydroxyketone 1 with malononitrile and
then reacted with 4-diethylaminobenzaldehyde to give
fluorophore 7; reacted with 1-hexyl-1,2,3,4-tetrahydro-
quinoline-6-carbaldehyde 5, which is prepared by alkylation
of tetrahydroquinoline18 followed by Vilsmeier reaction, to
give fluorophore 8; reacted with 2,3,6,7-tetrahydro-1H,5H-
pyrido[3,2,1-ij]quinoline-9-carbaldehyde 4, which was
prepared by Vilsmeier reaction of julolidine,19 to give
fluorophore 9.
the fluoro intermediate, which undergoes efficient aromatic
nucleophilic substitution with dihexylamine in pyridine.13
Compounds 16 and 17 were prepared by bromination of
1-hexyl-1,2,3,4-tetrahydro-quinoline and julolidine21 fol-
lowed by lithiation and trapped with 10 to make the respec-
tive 4-amino substituted a-ketols. Condensation of the
resulting ketols with malononitrile gives the desired DCDHF
dyes directly.
When these compounds were evaluated for fluorescence it
was immediately apparent that the removal of the alkene
resulted in enhanced quantum yields. In the search for
more red-shifted dyes that retain high quantum yield, the
corresponding naphthalene dyes might be appropriate.
The set of DCDHF dyes without a vinyl link was synthesized
originally for photorefractive applications13,16,20 (Scheme 2).
Synthesis of 11 begins with 4-fluorobromobenzene to make
NC
O
NC
O
TMSCl
Py
NC
NC
NC
F
OH
NC
OTMS
10
CN
CN
NC CN
Py
O
5
N
F
F
dihexylamine
Py
OH
5
Mg
THF
F
MgBr
Br
11
NC
NC
CN
O
O
N
N
Br
Br
O
N
Br
Br
N
5
OH
5
5
5
12
14
16
malononitrile Py
Br
n-BuLi -78°C to rt
Br
10
NC
NC
CN
O
OH
N
N
N
N
O
13
15
17
Scheme 2.

H. Wang et al. / Tetrahedron 63 (2007) 103–114
105
O
Br
n-BuLi
5
1-bromohexane
OH
Bucherer reaction
5
Br
Br
N
N
HO
H2N
10
5
20
5
19
malononitrile
NC
18
NC
CN
1,3-bromochloropropane
5
O
N
5
21
Br
N
Br
Br
NaOEt
N
N
23
EtO
Cl
22
n-BuLi 10
NC
NC
O
CN
malononitrile
N
O
N
HO
EtO
EtO
25
24
Scheme 3.
Fluorophore 21 was first synthesized, and found to be
excited at 514 nm and was used successfully as single-
molecule tracers in the cellular membrane.8 Although the
red shift is not as large as that resulting from addition of
an alkene group to the benzene ring, the quantum yield of
these dyes is higher than that of their benzene counterparts.
With these results in hand, we planned to make 2,6-
substituted DCDHF fluorophores with tetrahydroquinoline
rings. When we reacted 2-bromo-6-aminonaphthalene (18)
with 1-bromo-3-chloropropane the product resulting from
two-ring closure reactions was expected.22 However, and
to our surprise, instead only the intermediate 8-bromo-
4-(3-chloropropyl)-1,2,3,4-tetrahydrobenzo[f]quinoline 22
was separated as the major product (63% yield). Proof for
this substitution pattern comes from a crystal structure of
compound 30 derived from 22 (Fig. 3). All efforts to push
the 8-bromo-4-(3-chloropropyl)-1,2,3,4-tetrahydrobenzo[f]-
quinoline to close a second ring at temperatures up to 200 ꢀC
failed. As such, we were unable to prepare 9-bromo-2,3,5,6-
tetrahydro-1H,4H-3a-aza-benzo[de]anthracene23 by this
route. However, the chloro functionality in compound 22
is also useful. For example, a nucleophilic attack of ethoxide
to displace the chlorine giving 23 was accomplished. A
similar 1,2,3,4-tetrahydrobenzo[f ]quinoline with an alkyl
group on the amino group was synthesized in four steps.24
The ethyl ether product 23 after lithiation leads again to
the a-ketol 24 and desired DCDHF dye 25 (Scheme 3).
In addition, both of these dyes with vinyl linkages have also
been synthesized (Scheme 4) using the similar method found
in Scheme 1. The bromo compounds 26 and 23 were lithi-
ated and trapped with DMF to obtain aldehydes 27 and 29.
These two aldehydes were then condensed with compound
3 to give DCDHF fluorophores 28 and 30.
We also introduced this tetrahydroquinoline ring onto 1,4-
disubstituted naphthalene (Scheme 5). Alkylation of 1-naph-
thylamine led to both di- and mono-substituted compounds
31 and 32. Compound 31 was brominated21 and transformed
to a-ketol 36. However, because of the peri steric effect, the
NC
NC
n-BuLi
DMF
1,4-diiodobutane
Br
CHO
Br
3
Py
CN
N
N
H2N
N
O
26
27
28
NC
NC
n-BuLi
DMF
3
CHO
Br
CN
N
N
Py
N
O
EtO
EtO
EtO
23
29
30
Scheme 4.

106
H. Wang et al. / Tetrahedron 63 (2007) 103–114
O
Br
Br
NC
3
3
3
NC
1-bromobutane
DMF K2CO3
3
N
N
Br
N
CHO
H2N
Br Br
n-BuLi
N
3
Py
CN
3
3
3
DMF
3
O
31
34
35
33
NC
NC
OH
malononitrile
n-BuLi
10
3
N
CN
3
N
O
3
Py
O
3
36
NC
NC
3
1,3-bromochloropropane
N
DMF
POCl3
HN
N
CHO
N
3
Py
CN
3
3
3
O
32
37
38
39
Scheme 5.
ring condensation with malononitrile failed with the recov-
ery of reactants. So, we chose to convert this bromo com-
pound 33 to an aldehyde via lithiation and trapping with
DMF. Condensation of aldehyde 34 led to the desired fluoro-
phore 35. On the other hand, mono-substituted compound 32
can undergo ring formation with 1,3-bromochloropropane to
give 37 and Vilsmeier reaction to provide aldehyde 38.
Condensation of this aldehyde with heterocycle 3 in pyridine
resulted in the desired dye 39.
of one ring and 32 nm with addition of two rings while the
emission wavelength shifts to the red 15 nm with one ring
and 25 nm with two rings. In the group of benzene substrates
without the presence of vinyl group (group B), the emission
shifts are slightly smaller, 10 and 22 nm for the addition of
one ring and two rings, respectively. Also, the inclusion of
the donor nitrogen in the rings has a substantial influence
on the fluorescence quantum yield. It is increased almost
five times by comparing 11 with 17 and twice by comparing
7 with 9.
3. Results and discussion
The same trends were observed in more conjugated systems:
groups C, D, and E. In the 2,6-substituted naphthalene sys-
tems (groups C and D), the emission wavelength increased
upon constraining the amine twist (bathochromic shifts in
the emission of 31 and 28 nm, respectively). The quantum
yield was also enhanced; this is especially true for group
D, which exhibits an increase of almost two orders of mag-
nitude. The 1,4-substituted system (group E) is more like the
benzene systems (groups A and B), with 33 and 16 nm bath-
ochromic shifts, in absorption and emission, respectively.
The relevant physical properties of the different DCDHF
dyes in toluene are summarized in Table 1. As can be
seen, the absorption and emission wavelengths systemati-
cally increase as the nitrogen donor is constrained by one
ring and then by two rings. In the group of benzene
substrates with the presence of vinyl group (group A), the
absorption wavelength shifts to the red 19 nm with addition
Table 1. Characterization of DCDHF dyes with and without tetrahydroqui-
noline rings (all values in toluene)
With the spectral data plotted, it is clear that the absorption
and emission wavelengths both increase with the increasing
constraint of the donor amine twist. A previous theoretical
treatment of the electronic properties of the DCDHF
dyes11 showed that amine twist had little effect on the
ground- and excited-state energy surface and was not
responsible for the large viscosity sensitivity. The experi-
mental results here quantify the degree to which the exact
structure of the donor group shifts the spectra (Fig. 1).
max
abs
max
Group
Entry
l
l
em
(Stokes shift)
FF Toluene
(PMMA)
A
7
8
9
562
581
594
603 (41)
618 (37)
628 (34)
0.02 (0.39)
0.028
0.053
B
11
16
17
486
495
503
505 (19)
515 (20)
527 (24)
0.044 (0.92)
0.10
0.21
C
D
E
21
25
527
545
576 (49)
607 (62)
0.85 (0.98)
0.64
An important test for the utility of a fluorophore is its ability
to be imaged at the single-molecule level, which requires
strong fluorescence, weak coupling with dark states, and
photostability. Importantly, single-molecule imaging of de-
rivative 17 demonstrates that we maintained the favorable
photophysical properties of the parent molecule as shown
28
30
574
600
671 (97)
699 (99)
0.0049
0.30
35
39
538
571
661 (123)
677 (106)
0.0067
0.0096

H. Wang et al. / Tetrahedron 63 (2007) 103–114
Absorption Spectra Fluorescence Emission
107
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
11
16
17
7
8
9
400
450
500
550
600
650
700
500
550
600
650
700
750
800
Wavelength (nm)
Wavelength (nm)
Figure 1. Normalized absorption and fluorescence emission spectra for constrained derivatives and their parent molecules. Increasing the constraint on the
amine rotation red shifts the absorbance and emission (for structures see Table 1).
in Figure 2. To characterize the quality of a single-molecule
emitter using one simple parameter, we report the total num-
ber of photons emitted from a single fluorophore before pho-
tobleaching. Measurements on 182 individual molecules
yielded an average of Ntot,d¼1.5ꢁ105 photons detected per
molecule. The photon collection efficiency of our setup is
D¼hQFcollFoptFfilter, which is the product of the camera
quantum efficiency, the angular collection factor determined
by the objective numerical aperture, the transmission factor
through the objective and microscope optics, and the trans-
mission factor through the various filters, respectively.25
At the emission wavelengths, hQ¼85% for our camera; Fcoll
is assumed to be 50% for our high-NA objective;26 and we
measured Fopt and Ffilter to be 50 and 65%, respectively.
After recording single-molecule photobleaching distribu-
tions, which are exponential in shape as expected, a fit to
the exponential yields the average number of photons. Cor-
recting the Ntot,d value for the collection efficiency yields
was performed for fluorophores 16, 17, and 30. Figure 3
shows the numbering scheme for the atoms and the thermal
ellipsoids.
The torsion angles of important bonds in all compounds are
listed in Table 2. For fluorophores 16 and 17, the torsion
angles involving the amine bonding of the tetrahydroquino-
line ring and the benzene ring of these two fluorophores are
small and quite comparable (all <5ꢀ). The angles involving
the bonds between the benzene ring and the DCDHF accep-
tor are likewise very similar (all <10ꢀ). However, for fluoro-
phore 30, the tetrahydroquinoline ring becomes more planar
with the naphthalene ring (0.73ꢀ for the torsion angle involv-
ing the amine bonding of tetrahydroquinoline ring and
naphthalene ring) and the other chain of the amino group
becomes more off plane (ꢂ28.95ꢀ for the torsion angle in-
volving the bonds between the vinyl group and the DCDHF
acceptors).
a value for the total number of photons emitted, Ntot,e
¼
1.1ꢁ106 photons per molecule. This value is comparable
with the values of DCDHF-6 and R6G (2.4ꢁ106 and
1.9ꢁ106 photons emitted per molecule, respectively),27
both of which are among the best single-molecule fluoro-
phores.
To investigate the possible charge-transfer between the
amine donor and the DCDHF acceptor (the pair of limiting
resonance structures is shown in Fig. 4), the bond length be-
tween nitrogen–carbon groups present in the six-membered
rings would be expected to be shorter than a normal carbon
sp –nitrogen bond length (1.38 A).28 This is the case for 16
2
˚
˚
(C5–N1, 1.356(4) A) and 17 (C14–N4, 1.354(6) A). In addi-
tion, the bond length between the carbon of the acceptor and
˚
To obtain information about the ground-state configuration
of the molecules, an X-ray diffraction structural analysis
Figure 2. Epifluorescence images of single copies of 17 in a PMMA film imaged at 488-nm excitation. The surface was calculated from two position dimensions
and pixel intensity of a Gaussian-smoothed image.

108
H. Wang et al. / Tetrahedron 63 (2007) 103–114
NC
NC
NC
NC
CN
CN
N
N
O
O
Figure 4. Limiting resonance forms of fluorophore 17.
manifold predominantly control the changes in emission ob-
served in different hosts.11 Our current results suggest that
twists about the amine–benzene bond also noticeably affect
the fluorescence emission. A more detailed solution-phase
calculation including excited-state effects needs to be done
in the future in order to confirm the exact mechanism.
4. Conclusion
We have synthesized several examples of DCDHF fluoro-
phores with the amine donor either acyclic or constrained
in one or two tetrahydroquinoline rings. Generally, inclusion
of the donor in a ring annulated to the benzene or naphtha-
lene aromatic p-core results in a bathochromic shift of
absorption and emission accompanied by an increase in
the quantum yield. Introduction of the first tetrahydroquino-
line ring produces the largest effect, with a smaller effect
produced by the second ring. Favorable performance in
single-molecule fluorescence imaging is maintained for the
newly synthesized derivatives.
5. Experimental
5.1. General
Unless otherwise noted, all chemicals were used as received
from commercial suppliers. 1H (400 MHz) and 13C
(100 MHz) NMR spectra were obtained as solutions in the
indicated solvents, and chemical shifts are reported in parts
per million (ppm) downfield from internal standard TMS;
1H and 13C coupling constants are reported in hertz (Hz).
Compounds 7,5 11,13 and 218 were synthesized according
to the methods previously described. The a-(trimethyl-
siloxy)isobutyronitrile (10),33 6-bromo-2-naphthylamine
(18),29 and 6-bromo-2-(pyrrolidino)naphthalene (26)32
were synthesized following the literature procedures.
Figure 3. Thermal ellipsoid plots of DCDHF fluorophores 16, 17, and 30.
The ellipsoids are drawn at the 30% level.
the carbon of the six-membered ring would also be expected
to be shorter than that of a typical carbon sp2–carbon sp2
28
˚
bond (1.48 A). This is true for fluorophores 16 (C11–
˚
C13, 1.430(4) A) and 17 (C–C 1.429(5) A).
˚
Our previous calculations on the DCDHF parent molecule
showed that furan-dicyano twists on the excited state
Table 2. Torsion angles of fluorophores 16, 17, and 30
Solutions were prepared in toluene and bulk absorption and
emission spectra were obtained on Perkin–Elmer Lambda 19
UV–vis spectrometer and a SPEX Fluromax-2 fluorimeter,
respectively. Quantum yields were measured against stan-
dards with known quantum yields and were corrected for
differences in optical density and solvent refractive index.30
Fluorophore
Atoms involved
Torsion angle
16
C(13)–C(14)–N(4)–C(19)
C(15)–C(14)–N(4)–C(20)
C(16)–C(11)–C(3)–C(4)
C(12)–C(11)–C(3)–C(2)
O(1)–C(1)–C(5)–C(7)
C(2)–C(1)–C(5)–C(6)
ꢂ2.57
ꢂ4.45
ꢂ8.27
ꢂ10.65
2.58
2.85
Single-molecule samples were prepared by spin-casting 1%
(by mass) solutions of poly(methyl methacrylate) (PMMA)
in distilled toluene, doped with nanomolar fluorophore
concentrations, onto plasma-etched glass cover slips. After
drying, these samples were studied using a Nikon Diaphot
200 inverted microscope in an epifluorescence configura-
tion.25 Samples were illuminated using a continuous-wave
488-nm Novalux Protera 488-20 laser; the intensity at the
sample was approximately 0.5 kW/cm2. The emission was
collected through a 100ꢁ, 1.4 N.A. Nikon microscope
17
30
C(6)–C(5)–N(1)–C(9)
C(4)–C(5)–N(1)–C(1)
C(10)–C(11)–C(13)–C(20)
C(12)–C(11)–C(13)–C(14)
O(12)–C(15)–C(16)–C(17)
C(14)–C(15)–C(16)–C(18)
ꢂ2.94
ꢂ4.10
ꢂ11.86
ꢂ10.00
4.65
5.90
C(22)–C(21)–N(4)–C(23)
0.73
ꢂ28.95
ꢂ172.73
2.33
C(20)–C(21)–N(4)–C(26)
C(12)–C(11)–C(3)-C(4)
C(12)–C(11)–C(3)–C(2)

H. Wang et al. / Tetrahedron 63 (2007) 103–114
109
objective, filtered to remove scattered excitation light, and
imaged onto a back-illuminated frame-transfer Si CCD
camera (Roper Scientific MicroMax) with an integration
time of 100 ms.
(CDCl3): 176.4, 174.0, 150.5, 148.4, 132.5, 130.5, 123.2,
121.5, 113.0, 112.2, 111.9, 110.8, 107.8, 96.5, 51.8,
50.1, 31.6, 27.9, 26.8, 26.7, 26.6, 22.6, 21.3, 14.0; IR
(cmꢂ1): 2927, 2854, 2218, 1501. Anal. Calcd for
C27H30N4O: C, 76.03; H, 7.09; N, 13.13. Found: C, 76.23;
H, 7.15; N, 13.47.
5.2. Experimental procedure
5.2.1. 1-Hexyl-1,2,3,4-tetrahydroquinoline (5).18 A mix-
ture of tetrahydroquinoline (4.0 g, 30 mmol), 1-bromo-
hexane (3.8 g, 37 mmol), potassium carbonate (8.31 g,
60 mmol), and a catalytic amount of potassium iodide in
DMF (40 ml) was heated to 90 ꢀC overnight. After cooling,
the reaction mixture was poured into water and extracted
with ether. The organic layer was collected, washed with
brine, and dried over magnesium sulfate. The solvent was
removed and the residue was purified by flash chromato-
graphy (hexane) to give product as a clear liquid (4.8 g,
5.2.4. 9-Formyl-2,3,6,7-tetrahydro-1H,5H-benzo[ij]-
quinolizine (4).19 Following the procedure described for
compound 6, julolidine (1.0 g, 5.9 mmol) was reacted with
phosphorous oxychloride and anhydrous DMF to give the
1
product as a yellow oil (1.1 g, 93%). H NMR (400 MHz,
CDCl3): 9.61 (s, 1H), 7.31 (s, 2H), 3.31 (t, J¼11.6 Hz,
4H), 2.78 (t, J¼12.8 Hz, 4H), 1.98 (m, 4H); 13C NMR
(CDCl3): 190.1, 147.9, 129.5, 124.0, 120.3, 50.0, 27.7, 21.3.
5.2.5. 2-{3-Cyano-5,5-dimethyl-4-[(E)-2-(2,3,6,7-tetra-
hydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-vinyl]-5H-
furan-2-ylidene}-malononitrile (9). Following the
procedure described for compound 8, 9-formyl-2,3,6,7-
tetrahydro-1H,5H-benzo[ij]quinolizine (0.5 g, 2.5 mmol)
was reacted with 2-dicyanomethylen-3-cyano-4,5,5-
trimethyl-2,5-dihydrofuran 3 (0.5 g, 2.4 mmol) in pyridine
(20 ml) to give the product as blue crystals (0.4 g, 44%).
1
74%). H NMR (400 MHz, CDCl3): 7.06 (m, 1H), 6.95 (d,
1H), 6.57 (m, 2H), 3.30 (t, J¼11.2 Hz, 2H), 3.25 (t,
J¼15.2 Hz, 2H), 2.77 (t, J¼12.8 Hz, 2H), 1.97 (m, 2H),
1.59 (m, 2H), 1.35 (m, 6H), 0.93 (t, J¼13 Hz, 3H); 13C
NMR (CDCl3): 145.5, 129.2, 127.2, 122.2, 115.3, 110.6,
51.7, 49.6, 31.9, 28.4, 27.1, 26.3, 22.9, 22.4, 14.2.
5.2.2. 1-Hexyl-1,2,3,4-tetrahydroquinoline-6-carbalde-
hyde (6).18 Phosphorous oxychloride (0.78 g, 5.0 mmol)
was added dropwise to anhydrous DMF (1.11 g,
15.2 mmol) under nitrogen with ice-bath cooling. After
addition, the mixture was stirred at room temperature for
30 min, transferred to a flask containing 1-hexyl-1,2,3,4-
tetrahydroquinoline 5 (1.0 g, 4.6 mmol) and the resulting
mixture was heated to 90 ꢀC for 4 h. After cooling, water
(100 ml) was added to the reaction mixture and the mixture
was neutralized with sodium bicarbonate. The mixture was
then extracted with ethyl acetate, washed with brine, and
dried over magnesium sulfate. Solvent was removed under
vacuum and the residue was purified by flash chromato-
graphy (hexane/ethyl acetate, 4:1) to give product as a yellow
oil (0.9 g, 80%). 1H NMR (400 MHz, CDCl3): 9.67 (s, 1H),
7.55 (d, J¼8.4 Hz, 1H), 7.47 (s, 1H), 6.58 (d, J¼8.4 Hz, 1H),
3.41 (t, J¼11.2 Hz, 2H), 3.34 (t, J¼15.2 Hz, 2H), 2.80 (t, J¼
12.0 Hz, 2H), 1.97 (m, 2H), 1.62 (m, 2H), 1.36 (m, 6H), 0.88
(t, 3H); 13C NMR (CDCl3): 190.0, 150.3, 131.3, 130.4,
124.5, 121.6, 109.3, 51.5, 49.8, 31.7, 28.0, 26.8, 26.3,
22.6, 21.5, 14.0.
DSC, mp: 285 ꢀC; UV–vis (CH2Cl2): lmax¼620 nm, 3max
¼
8.09ꢁ104 l cmꢂ1 molꢂ1; 1H NMR (400 MHz, CDCl3): 7.53
(d, J¼16.0 Hz, 1H), 7.15 (s, 2H), 6.67 (d, J¼16.0 Hz, 1H),
3.40 (t, J¼11.6 Hz, 4H), 2.78 (t, J¼12.4 Hz, 4H), 2.02 (m,
4H), 1.57 (s, 6H); 13C NMR (CDCl3): 173.8, 148.5, 148.4,
130.2, 121.9, 113.2, 112.4, 112.1, 107.3, 96.3, 50.4, 27.5,
26.9, 21.0; IR (cmꢂ1): 2937, 2836, 2204, 1536. Anal. Calcd
for C24H22N4O: C, 75.37; H, 5.80; N, 14.65. Found: C,
74.99; H, 5.58; N, 14.97.
5.2.6. 6-Bromo-1-hexyl-1,2,3,4-tetrahydroquinoline (12).
A solution of 1-hexyl-1,2,3,4-tetrahydroquinoline 5 (2.0 g,
9.2 mmol) in dichloromethane (20 ml) cooled to ꢂ10 ꢀC
was treated with small portions of 2,4,4,6-tetrabromo-
2,5-cyclohexadien-1-one (3.7 g, 9.2 mmol) such that the
temperature of the solution was maintained below 0 ꢀC.
The solution was stirred at room temperature for 45 min,
washed with aqueous sodium hydroxide (3ꢁ50 ml, 2 M)
and then washed with brine, and dried over magnesium sul-
fate. After the removal of the solvent the residue was purified
by flash chromatography (hexane) to give the product (2.3 g,
65%). 1H NMR (400 MHz, CDCl3): 7.11 (dd, J¼8.8,
2.4 Hz), 7.04 (d, J¼2.4 Hz, 1H), 6.43 (d, J¼8.8 Hz, 1H),
3.26 (t, 2H), 3.21 (t, 2H), 2.75 (t, 2H), 1.94 (m, 2H), 1.57
(m, 2H), 1.34 (m, 6H), 0.92 (t, 3H); 13C NMR (CDCl3):
144.3, 131.4, 129.6, 127.1, 115.2, 112.0, 51.6, 49.3, 31.8,
28.1, 27.0, 26.0, 22.7, 22.0, 14.1; IR (cmꢂ1): 2927, 2856,
1497. HRMS m/z calcd for C15H22BrN [M+H]: 296.1014.
Found: 296.1009.
5.2.3. 2-{3-Cyano-4-[(E)-2-(1-hexyl-1,2,3,4-tetrahydro-
quinolin-6-yl)-vinyl]-5,5-dimethyl-5H-furan-2-ylidene}-
malononitrile (8). A mixture of 1-hexyl-1,2,3,4-tetrahydro-
quinoline-6-carbaldehyde 6 (0.6 g, 2.45 mmol), 2-dicyano-
methylen-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran 3 (0.48 g,
2.40 mmol), pyridine (20 ml), and several drops of acetic
acid was stirred at room temperature overnight. Pyridine
was distilled out under vacuum. The residue was precipitated
from CH2Cl2/hexane and recrystallized from CH2Cl2/meth-
anol to give the product as blue crystals (0.5 g, 49%). DSC,
5.2.7. 1-(1-Hexyl-1,2,3,4-tetrahydroquinolin-6-yl)-2-
hydroxy-2-methyl-propan-1-one (14). The 6-bromo-1-
hexyl-1,2,3,4-tetrahydroquinoline (1.63 g, 4.2 mmol) was
dissolved in anhydrous THF (20 ml) with magnetic stirring.
The solution was cooled down to ꢂ78 ꢀC and 2.5 M of
n-BuLi in hexane (2.0 ml, 5.0 mmol) was added. The reac-
tion mixture was stirred at ꢂ78 ꢀC for 1 h and 2-trimethyl-
silyloxy-2-cyano-propane 10 (1.2 g, 7.6 mmol) was added
via syringe. The reaction mixture was then allowed to
mp: 208 ꢀC; UV–vis (CH2Cl2): lmax¼607 nm, 3max
¼
1.74ꢁ104 l cmꢂ1 molꢂ1
;
1H NMR (400 MHz, CDCl3):
7.59 (d, J¼15.6 Hz, 1H), 7.38 (dd, J¼2.0, 8.8 Hz, 1H),
7.31 (d, 1H), 6.70 (d, J¼15.6 Hz, 1H), 6.60 (d, J¼8.8 Hz,
1H), 3.48 (t, J¼12 Hz, 2H), 3.40 (t, J¼15.6 Hz, 2H), 2.80
(t, J¼12.4 Hz, 2H), 2.00 (m, 2H), 1.76 (s, 6H), 1.66 (m,
2H), 1.36 (m, 6H), 0.93 (t, J¼14.0 Hz, 3H); 13C NMR

110
H. Wang et al. / Tetrahedron 63 (2007) 103–114
warm to room temperature and stirred overnight. Next, 10%
hydrochloric acid (20 ml) was added to the flask with vigor-
ous stirring for 6 h until TLC shows hydrolysis was com-
plete. Sodium bicarbonate was added carefully to the
mixture to neutralize the hydrochloric acid and the resulting
mixture was extracted with ether. The organic layer was
washed with brine and dried with anhydrous magnesium
sulfate. Solvent was removed by rotary evaporator and the
residue was purified by flash chromatography (hexane/ethyl
acetate, 4:1) to give the product as a light yellow liquid
(CDCl3): 201.2, 147.0, 130.0, 119.6, 118.4, 74.8, 49.9,
29.4, 27.8, 21.3; IR (cmꢂ1): 3425, 2915, 2850, 1590.
HRMS m/z calcd for C16H21NO2 [M+Na]: 282.1470. Found:
282.1464.
5.2.11. 3-Cyano-2-dicyanomethylene-4-(4-tetrahydroqui-
noline)-5,5-dimethyl-2,5-dihydrofuran (17). Following
the procedure described for compound 16, 2-hydroxy-2-
methyl-1-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-
9-yl)-propan-1-one 15 (0.4 g, 1.5 mmol) was reacted with
malononitrile (1.0 g, 15 mmol) in pyridine (50 ml) to give
the product as violet crystals (0.20 g, 37%). DSC, mp:
247 ꢀC; UV–vis (CH2Cl2): lmax¼517 nm, 3max¼9.04ꢁ
1
(1.0 g, 78%). H NMR (400 MHz, CDCl3): 7.82 (d, J¼
8.8 Hz, 1H), 7.73 (s, 1H), 6.52 (d, J¼8.8 Hz, 1H), 3.40 (t, J¼
11.2 Hz, 2H), 3.33 (t, J¼15.2 Hz, 2H), 2.80 (t, J¼12.4 Hz,
2H), 1.99 (m, 2H), 1.65 (s, 6H), 1.62 (m, 2H), 1.36 (m,
6H), 0.93 (t, J¼14.0 Hz, 3H); 13C NMR (CDCl3): 201.1,
149.4, 131.7, 131.1, 121.1, 118.7, 108.6, 74.9, 51.4, 49.7,
31.7, 29.3, 29.2, 28.1, 26.8, 26.3, 22.6, 21.6, 14.0; IR
(cmꢂ1): 3419, 2928, 1589. HRMS m/z calcd for
C19H29NO2 [M+H]: 303.2198. Found: 303.2206.
104 l cmꢂ1 molꢂ1 1H NMR (400 MHz, CDCl3): 7.75 (s,
;
2H), 3.58 (t, J¼12.4 Hz, 4H), 2.94 (t, J¼12.4 Hz, 4H), 2.17
(m, 4H), 1.97 (s, 6H); 13C NMR (CDCl3): 177.3, 173.0,
149.2, 129.5, 121.3, 113.6, 113.4, 112.43, 112.39, 96.8,
50.3, 27.7, 27.4, 20.5; IR (cmꢂ1): 2939, 2844, 2218, 2203,
1497. Anal. Calcd for C22H20N4O: C, 74.14; H, 5.66; N,
15.72. Found: C, 74.28; H, 6.08; N, 16.02.
5.2.8. 3-Cyano-2-dicyanomethylen-4-(1-hexyl-1,2,3,4-tet-
rahydro-quinolin-6-yl)-5,5-dimethyl-2,5-dihydrofuran
(16). A mixture of 1-(1-hexyl-1,2,3,4-tetrahydroquinolin-6-
yl)-2-hydroxy-2-methyl-propan-1-one 14 (1.0 g, 3.3 mmol),
malononitrile (1.0 g, 15 mmol), and pyridine (50 ml) was
stirred overnight at room temperature with several drops
of acetic acid. The reaction mixture was poured into ice
water (300 ml) with stirring and refrigerated overnight.
The precipitate was filtered off and recrystallized from
dichloromethane/methanol to give the product as violet crys-
tals (0.5 g, 38%). DSC, mp: 202 ꢀC; UV–vis (CH2Cl2):
5.2.12. 8-Bromo-4-(3-chloropropyl)-1,2,3,4-tetrahydro-
benzo[f]quinoline (22). A 200 ml round-bottom flask was
equipped with a small glass column filled with molecular
˚
sieves (4 A, 5 g) and a condenser. Next, 6-bromo-2-
naphthylamine (3.0 g, 13.56 mmol), sodium carbonate
(15.0 g, 54 mmol), and 1,3-bromochloropropane (30.0 g,
191.1 mmol) were added and the reaction mixture was
heated with vigorous stirring under an atmosphere of nitro-
gen while the bath temperature was gradually increased
(70 ꢀC/1 h, 100 ꢀC/2 h, 160 ꢀC/12 h). After cooling, the
mixture was poured into 1 N potassium hydroxide
(150 ml) and extracted with ether. The organic layer was fur-
ther washed with brine, dried over magnesium sulfate, and
purified by flash chromatography (hexane/ethyl acetate:
99:1) to give the product as a yellowish solid (2.9 g, 63%).
lmax¼508 nm, 3max¼9.59ꢁ104 l cmꢂ1 molꢂ1
;
1H NMR
(400 MHz, CDCl3): 7.87 (dd, J¼2.4, 9.2 Hz, 1H), 7.74 (d,
J¼2.8 Hz, 1H), 6.65 (d, J¼9.2 Hz, 1H), 3.50 (t, J¼
11.6 Hz, 2H), 3.42 (t, J¼15.2 Hz, 2H), 2.80 (t, J¼12.4 Hz,
2H), 2.01 (m, 2H), 1.84 (s, 6H), 1.65 (m, 2H), 1.35 (m,
6H), 0.93 (t, J¼14.0 Hz, 3H); 13C NMR (CDCl3): 177.2,
173.3, 151.0, 131.4, 130.7, 122.7, 113.5, 113.2, 113.1,
112.2, 110.6, 97.0, 51.8, 50.2, 31.6, 28.0, 27.8, 26.7, 26.6,
22.6, 21.1, 14.0; IR (cmꢂ1): 2931, 2858, 2220, 2201, 1563.
Anal. Calcd for C25H28N4O: C, 74.97; H, 7.05; N, 13.99.
Found: C, 74.58; H, 6.98; N, 13.59.
1
DSC, mp: 84 ꢀC; H NMR (300 MHz, CDCl3): 7.80 (d,
J¼2.1 Hz, 1H), 7.60 (d, J¼9.0 Hz, 1H), 7.49 (d, J¼9.0 Hz,
1H), 7.45 (dd, J¼11.1 Hz, 1H), 7.10 (d, J¼9.0 Hz, 1H),
3.53 (m, 4H), 3.55 (t, J¼10.8 Hz, 2H), 3.03 (t, J¼12.9 Hz,
2H), 2.11 (m, 4H); 13C NMR (CDCl3): 143.2, 131.9,
130.2, 129.5, 128.0, 126.6, 121.7, 116.1, 115.0, 113.3,
50.6, 49.7, 31.6, 30.4, 23.8; IR (cmꢂ1): 2915, 2850, 1502.
HRMS m/z calcd for C16H17BrClN [M+H]: 338.0306.
Found: 338.0301.
5.2.9. 9-Bromo-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-
ij]quinoline (13).31 Following the procedure described for
compound 12, julolidine (1.3 g, 7.6 mmol) in dichloro-
methane (20 ml) was reacted with 2,4,4,6-tetrabromo-2,5-
cyclohexadien-1-one (3.05 g, 7.5 mmol) to give the product
5.2.13. 8-Bromo-4-(3-ethoxypropyl)-1,2,3,4-tetrahydro-
benzo[f]quinoline (23). A mixture of 8-bromo-4-(3-chloro-
propyl)-1,2,3,4-tetrahydrobenzo[f]quinoline 22 (1.5 g,
4.4 mmol), sodium ethoxide (0.48 g, 7.5 mmol), and ethanol
(20 ml) was refluxed for 24 h. After cooling, the reaction
mixture was poured into brine (150 ml) and extracted with
ether. The organic layer was collected and dried over magne-
sium sulfate. The solvent was removed and the residue was
purified by flash chromatography (ethyl acetate/hexane,
1
as clear liquid (1.1 g, 60%). H NMR (400 MHz, CDCl3):
6.90 (s, 2H), 3.14 (t, J¼11.6 Hz, 4H), 2.75 (t, J¼13.2 Hz,
4H), 1.99 (m, 4H); 13C NMR (CDCl3): 143.2, 129.2,
123.5, 107.2, 50.1, 27.7, 21.8.
5.2.10. 2-Hydroxy-2-methyl-1-(2,3,6,7-tetrahydro-
1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-propan-1-one (15).
Following the procedure described for compound 10, 9-
bromo-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinoline
13 (0.7 g, 2.8 mmol) was reacted with 2.5 M of n-BuLi
in hexane (1.4 ml, 3.5 mmol) and 2-trimethylsilyloxy-2-
cyano-propane (1.2 g, 7.6 mmol) to give the product as
1
1:19) to give product as yellow liquid (1.0 g, 65%). H
NMR (400 MHz, CDCl3): 7.77 (d, J¼2.0 Hz, 1H), 7.58 (d,
J¼9.2 Hz, 1H), 7.45 (d, J¼8.8 Hz, 1H), 7.42 (dd, J¼
11.6 Hz, 1H), 7.11 (d, J¼9.2 Hz, 1H), 3.48 (m, 6H), 3.31
(t, J¼10.8 Hz, 2H), 3.00 (t, J¼13.2 Hz, 2H), 2.07 (m, 2H),
1.86 (m, 2H), 1.24 (t, J¼14.0 Hz, 3H); 13C NMR (CDCl3):
143.5, 131.7, 129.9, 129.2, 127.6, 126.2, 123.2, 116.1,
114.4, 112.4, 67.8, 66.3, 49.1, 49.0, 27.6, 23.7, 21.8, 15.3;
1
a light yellow liquid (0.5 g, 70%). H NMR (400 MHz,
CDCl3): 7.57 (s, 2H), 3.30 (t, J¼11.6 Hz, 4H), 2.77 (t,
J¼12.8 Hz, 4H), 1.98 (m, 4H), 1.64 (s, 6H); 13C NMR

H. Wang et al. / Tetrahedron 63 (2007) 103–114
111
IR (cmꢂ1): 2928, 2858, 1588, 1115. HRMS m/z calcd for
C18H22BrNO [M+Na]: 370.0782. Found: 370.0779.
130.9, 130.1, 126.4, 124.8, 123.5, 116.3, 104.6, 47.7, 25.5;
IR (cmꢂ1): 2945, 2862, 1678, 1561. Anal. Calcd for
C15H15NO: C, 79.97; H, 6.71; N, 6.22. Found: C, 80.30;
H, 6.81; N, 6.15.
5.2.14. 1-[4-(3-Ethoxypropyl)-1,2,3,4-tetrahydrobenzo[f]-
quinolin-8-yl]-2-hydroxy-2-methyl-propan-1-one (24).
Following the procedure described for compound 14,
8-bromo-4-(3-ethoxypropyl)-1,2,3,4-tetrahydrobenzo[f]qui-
noline 23 (0.5 g, 1.44 mmol) was reacted with 2.5 M of
n-BuLi in hexane (1.5 ml, 3.75 mmol) and 2-trimethylsilyl-
oxy-2-cyano-propane33 (0.76 g, 4.80 mmol) to give the
product as a yellowish liquid (0.35 g, 68%). 1H NMR
(400 MHz, CDCl3): 8.41 (d, J¼2.0 Hz, 1H), 7.99 (dd, J¼
9.2 Hz, 1H), 7.70 (d, J¼8.8 Hz, 1H), 7.66 (d, J¼9.2 Hz,
1H), 7.16 (d, J¼9.2 Hz, 1H), 3.54 (t, J¼14.0 Hz, 2H), 3.50
(m, 4H), 3.38 (t, J¼10.8 Hz, 2H), 3.03 (t, J¼13.2 Hz, 2H),
2.09 (m, 2H), 1.89 (m, 2H), 1.72 (s, 6H), 1.25 (t, J¼
14.0 Hz, 3H); 13C NMR (CDCl3): 203.4, 145.8, 135.4,
132.7, 129.5, 126.1, 124.9, 124.6, 121.2, 115.5, 111.8,
75.7, 67.6, 66.3, 49.2, 48.7, 29.0, 27.6, 23.5, 21.6, 15.3; IR
(cmꢂ1): 3403, 2972, 2929, 2860. HRMS m/z calcd for
C22H29NO3 [M+Na]: 378.2029. Found: 378.0245.
5.2.17. 1-(3-Cyano-2-dicyanomethylen-5,5-dimethyl-2,5-
dihydrofuran-4-yl)-2-[2-(6-pyrrolidinonaphthyl)]ethane
(28). 2-Pyrrolidino-6-naphthaldehyde (225 mg, 1.0 mmol)
and
3-cyano-2-dicyanomethylen-4,5,5-trimethyl-2,5-di-
hydrofuran (200 mg, 1.0 mmol) were dissolved in 10 ml of
pyridine. Two drops of acetic acid was added to the solution
and the mixture was stirred for 24 h at room temperature.
Pyridine was removed by an efficient oil pump with a dry
ice trap at room temperature. The residue was purified by
flash chromatography with hexane/dichloromethane mixture
as eluant (1:1 to pure dichloromethane) to give a blue solid
(330 mg, 72%). UV–vis (CH2Cl2): lmax¼605 nm, 3max
¼
1
5.81ꢁ104 l cmꢂ1 molꢂ1; H NMR (400 MHz, CDCl3) 7.91
(s, 1H), 7.80 (d, J¼16 Hz, 1H), 7.75 (d, J¼8.8 Hz, 1H),
7.63 (d, J¼1.2 Hz, 1H), 7.04 (dd, J¼9.2, 2.4 Hz, 1H), 7.00
(d, J¼15.6 Hz, 1H), 6.75 (d, J¼2.4 Hz, 1H), 3.51 (m, 4H),
2.13 (m, 4H), 1.82 (s, 6H); 13C NMR (CDCl3): 174.0,
148.6, 148.4, 138.1, 134.2, 131.1, 127.2, 126.8, 125.5,
123.7, 116.7, 112.3, 111.5, 111.4, 111.0, 105.1, 97.1, 47.9,
26.7, 25.5; IR (cmꢂ1): 2950, 2848, 2220, 1556. Anal. Calcd
for C26H22N4O: C, 76.83; H, 5.46; N, 13.78. Found: C,
76.77; H, 6.58; N, 13.64.
5.2.15. 8-(3-Dicyanomethylen-2-cyano-5,5-dimethyl-3,5-
dihydrofuryl)-4-(3-ethoxypropyl)-1,2,3,4-tetrahydro-
benzo[f]quinoline (21). Following the procedure described
for compound 16, 8-(2-methyl-2-hydroxy-1-oxopropyl)-4-
(3-ethoxypropyl)-1,2,3,4-tetrahydrobenzo[f]quinoline (0.3 g,
0.84 mmol) was reacted with malononitrile (0.4 g,
6.0 mmol) in pyridine (50 ml) to give the product as a green
solid (0.12 g, 32%). DSC, mp: 216 ꢀC; UV–vis (CH2Cl2):
5.2.18. 1-(3-Ethoxypropyl)-1,2,3,4-tetrahydrobenzo[g]-
quinoline-7-carbaldehyde (29). 8-Bromo-4-(3-ethoxy-
propyl)-1,2,3,4-tetrahydrobenzo[f]quinoline 23 (0.5 g,
1.44 mmol) was dissolved in anhydrous THF (20 ml) with
magnetic stirring. The solution was cooled down to
ꢂ78 ꢀC and 2.5 M of n-BuLi in hexane (0.8 ml, 2 mmol)
was added. The reaction mixture was stirred at ꢂ78 ꢀC for
1 h. Next, anhydrous DMF (0.8 ml, 11.7 mmol) was added
via syringe. The reaction mixture was then allowed to
warm gradually to room temperature and stirred overnight.
Hydrochloric acid (10%, 20 ml) was added to the flask and
the mixture was stirred vigorously for 6 h until TLC showed
that the hydrolysis was complete. Sodium bicarbonate was
added carefully to the mixture to neutralize hydrochloric
acid and the resulting mixture was extracted with ether.
The organic layer was washed with brine and dried with an-
hydrous magnesium sulfate. Solvent was removed by rotary
evaporation and the residue was purified by flash chromato-
graphy (hexane/ethyl acetate, 19:1) to give the product as a
light yellow liquid (0.30 g, 55%). 1H NMR (400 MHz,
CDCl3): 10.01 (s, 1H), 8.10 (d, J¼1.6 Hz), 7.85 (dd,
J¼8.8, 1.6 Hz, 1H), 7.75 (d, J¼8.4 Hz, 1H), 7.70 (d, J¼
8.4 Hz, 1H), 3.56 (t, J¼14.4 Hz, 2H), 3.50 (m, 4H), 3.40
(t, J¼10.8 Hz, 2H), 3.05 (t, J¼13.2 Hz, 2H), 2.10 (m, 2H),
1.91 (m, 2H), 1.27 (t, J¼14.0 Hz, 3H); 13C NMR (CDCl3):
191.8, 146.0, 136.4, 135.3, 129.7, 129.3, 125.0, 123.5,
121.9, 115.4, 112.2, 67.6, 66.3, 49.2, 48.8, 27.6, 23.7,
21.6, 15.3; IR (cmꢂ1): 2929, 2859, 1679, 1599. HRMS m/z
calcd for C19H23NO2 [M+Na]: 320.1626. Found: 320.1625.
lmax¼569 nm, 3max¼4.09ꢁ104 l cmꢂ1 molꢂ1
;
1H NMR
(400 MHz, CDCl3): 8.30 (d, J¼2.4 Hz, 1H), 7.92 (dd, J¼
9.2 Hz, 1H), 7.75 (d, J¼9.6 Hz, 1H), 7.66 (d, J¼9.2 Hz,
1H), 7.21 (d, J¼9.2 Hz, 1H), 3.59 (t, J¼6.8 Hz, 2H), 3.47
(m, 6H), 3.02 (t, J¼12.8 Hz, 2H), 2.11 (m, 2H), 1.91 (m,
8H), 1.25 (t, J¼14.0 Hz, 3H); 13C NMR (CDCl3): 176.6,
175.4, 147.7, 135.7, 132.8, 130.6, 125.1, 124.5, 122.6,
118.2, 116.1, 112.6, 112.5, 112.4, 67.3, 66.4, 49.4, 48.8,
27.7, 27.5, 23.2, 21.2, 15.3; IR (cmꢂ1): 2941, 2857, 2219,
1518. HRMS m/z calcd for C28H28N4O2 [M+Na]:
475.2110. Found: 475.2111.
5.2.16. 2-Pyrrolidino-6-naphthaldehyde (27). In a dry
50 ml round-bottom flask were placed 6-bromo-2-(pyrroli-
dino)naphthalene (1.0 g, 3.6 mmol) and 40 ml anhydrous
diethyl ether. The mixture was cooled to ꢂ78 ꢀC and
2.5 ml (5.0 mmol) of n-BuLi in hexane (2.5 M) was added
to this stirred mixture over 10 min. The resulting mixture
was stirred for an additional 1 h at ꢂ78 ꢀC and then DMF
(1 ml, 12.9 mmol) was added to the resulting mixture via
a syringe over 5 min. After completion of addition the tem-
perature was allowed to increase to room temperature and
stirred for 8 h. The reaction was quenched with 30 ml water
and the mixture was extracted with dichloromethane and the
organic layer was washed with water, brine, and dried with
anhydrous MgSO4. Solvent was removed by rotary evapora-
tion and the residue was purified by silica gel chromato-
graphy with hexane and a hexane/CH2Cl2 (9:1) mixture as
eluants to give a yellow solid (0.68 g, 84%). 1H NMR
(400 MHz, CDCl3): 10.0 (s, 1H), 8.15 (s, 1H), 7.83 (dd, J¼
8.8, 2.0 Hz, 2H), 7.65 (d, J¼8.8 Hz, 1H), 7.04 (dd, J¼9.2,
2.4 Hz, 1H), 6.75 (d, J¼2.0 Hz, 1H), 3.47 (m, 2H), 2.10
(m, 2H); 13C NMR (CDCl3): 191.8, 148.2, 138.9, 135.1,
5.2.19. 2-(3-Cyano-4-{(E)-2-[4-(3-ethoxypropyl)-1,2,3,4-
tetrahydrobenzo[f]quinolin-8-yl]-vinyl}-5,5-dimethyl-
5H-furan-2-ylidene)-malononitrile (30). Following the
procedure described for compound 8, 1-(3-ethoxypropyl)-
1,2,3,4-tetrahydrobenzo[g]quinoline-7-carbaldehyde
29

112
H. Wang et al. / Tetrahedron 63 (2007) 103–114
(0.15 g, 0.50 mmol) was reacted with 2-dicyanomethylen-3-
cyano-4,5,5-trimethyl-2,5-dihydrofuran 3 (0.07 g, 0.74 mmol)
in pyridine (20 ml) to give the product as blue crystals
(0.12 g, 50%). DSC, mp: 198 ꢀC; UV–vis (CH2Cl2):
(d, J¼8.0 Hz, 1H), 3.34 (t, J¼14.8 Hz, 4H), 1.59 (m, 4H),
1.30 (m, 4H), 0.89 (t, J¼14.8 Hz, 6H); 13C NMR (CDCl3):
192.3, 155.72, 138.3, 128.7, 125.7, 125.5, 125.0, 114.9,
53.1, 29.2, 20.4, 13.9; IR (cmꢂ1): 2930, 2862, 1665, 1460.
HRMS m/z calcd for C19H25NO [M+Na]: 306.1834. Found:
306.1840.
lmax¼627 nm, 3max¼4.42ꢁ104 l cmꢂ1 molꢂ1
;
1H NMR
(400 MHz, CDCl3): 7.88 (d, J¼2.0 Hz, 1H), 7.78 (d, J¼
16.0 Hz, 1H), 7.73 (d, J¼9.2 Hz, 1H), 7.65 (m, 2H), 7.18
(d, J¼9.2 Hz, 1H), 7.01 (d, J¼16.0 Hz, 1H), 3.60 (t, 2H),
3.52 (m, 4H), 3.45 (t, 2H), 3.07 (t, 2H), 2.15 (m, 2H), 1.93
(m, 2H), 1.83 (s, 6H), 1.27 (t, J¼14.0 Hz, 3H); 13C NMR
(CDCl3): 175.9, 173.9, 148.4, 146.5, 135.5, 134.4, 129.7,
126.4, 125.7, 123.7, 122.8, 115.6, 112.8, 112.3, 111.55,
111.49, 111.07, 97.1, 96.4, 67.5, 66.4, 49.4, 48.8, 27.7,
26.7, 23.5, 21.5, 15.3; IR (cmꢂ1): 2927, 2853, 2220, 1560.
HRMS m/z calcd for C30H30N4O2 [M+Na]: 501.2266.
Found: 501.2268.
5.2.23. 1-(3-Cyano-2-dicyanomethylen-5,5-dimethyl-2,5-
dihydrofuran-4-yl)-2-{2-[N,N-dibutylaminonaphthyl]}-
ethane (35). Following the procedure described for
compound 8, 4-N,N-dibutylnaphthaldehyde 34 (0.5 g,
1.77 mmol) was reacted with 2-dicyanomethylen-3-cyano-
4,5,5-trimethyl-2,5-dihydrofuran 3 (0.32 g, 1.60 mmol) in
pyridine (20 ml) to give the product as blue crystals
(0.45 g, 55%). UV–vis (CH2Cl2): lmax¼583 nm, 3max
¼
2.22ꢁ104 l cmꢂ1 molꢂ1
;
1H NMR (400 MHz, CDCl3):
8.68 (d, J¼16.0 Hz, 1H), 8.21 (d, J¼8.0 Hz, 1H), 8.11 (d,
J¼8.4 Hz, 1H), 8.03 (d, J¼8.4 Hz, 1H), 7.66 (m, 1H), 7.56
(m, 1H), 7.14 (d, J¼8.4 Hz, 1H), 7.03 (d, J¼16.0 Hz, 1H),
3.40 (t, J¼14.8 Hz, 3H), 1.87 (s, 6H), 1.58 (m, 4H), 1.33
(m, 4H), 0.89 (t, J¼14.4 Hz, 6H); 13C NMR (CDCl3):
176.0, 174.0, 155.6, 143.8, 133.8, 129.0, 128.3, 127.7,
126.0, 125.6, 123.6, 122.6, 116.1, 112.5, 112.3, 111.4,
111.4, 97.2, 53.2, 29.4, 26.8, 20.4, 13.9. IR (cmꢂ1): 2957,
2931, 2871, 2216, 2203, 1539. Anal. Calcd for
C30H32N4O: C, 77.55; H, 6.94; N, 12.06. Found: C, 77.29;
H, 7.33; N, 12.34.
5.2.20. N,N-Dibutylnaphthylamine (31) and N-butyl-
naphthylamine (32).34 A mixture of 1-naphthylamine
(14.3 g, 100 mmol), 1-bromobutane (30 g, 220 mmol), po-
tassium carbonate (55 g, 400 mmol), and ethanol (300 ml)
was refluxed for 48 h. The mixture was filtered and the fil-
trate was extracted with ether, washed with brine, and dried
over magnesium sulfate. The solvent was removed and the
residue was purified by flash chromatography to give the
disubstituted product as a clear liquid (8.0 g, 31%). 1H
NMR (400 MHz, CDCl3): 8.31 (d, J¼7.2 Hz, 1H), 7.78 (d,
J¼8.0 Hz, 1H), 7.51 (d, J¼8.0 Hz, 1H), 7.42 (m, 2H), 7.38
(t, 1H), 7.13 (d, J¼6.4 Hz, 1H), 3.11 (t, J¼14.8 Hz, 4H),
1.46 (m, 4H), 1.30 (m, 4H), 0.83 (t, J¼14.8 Hz, 6H); 13C
NMR (CDCl3): 148.8, 135.0, 131.3, 128.2, 125.7, 125.6,
125.1, 124.4, 123.2, 118.0, 54.2, 29.4, 20.6, 14.1. The
mono-substituted product was also obtained from the later
5.2.24. 1-Butyl-1,2,3,4-tetrahydrobenzo[h]quinoline (37).
Following the procedure described for compound 22,
2-N-butylnaphthylamine (1.1 g, 7.4 mmol), sodium carbon-
ate (3.0 g, 28 mmol), and 1,3-bromochloropropane (15.0 g,
95.5 mmol) were reacted together to give a crude liquid as
a mixture of the desired product and 1,3-bromochloro-
propane, which is used in the next step without purification.
1
fractions (12.0 g, 61%). H NMR (400 MHz, CDCl3): 7.84
(m, 2H), 7.47 (m, 2H), 7.40 (m, 1H), 7.27 (d, J¼9.2 Hz,
1H), 6.66 (d, J¼7.6 Hz), 4.34 (s, 1H), 3.32 (t, J¼14.0 Hz,
2H), 1.81 (m, 2H), 1.58 (m, 2H), 1.06 (t, J¼14.8 Hz, 3H);
13C NMR (CDCl3): 144.0, 134.6, 128.9, 127.0, 125.9,
124.8, 123.7, 120.1, 117.3, 104.4, 44.1, 31.8, 20.8, 14.3.
5.2.25. 1-Butyl-1,2,3,4-tetrahydrobenzo[h]quinoline-6-
carbaldehyde (38). Following the procedure described for
compound 6, the crude 1-butyl-1,2,3,4-tetrahydrobenzo[h]-
quinoline 37 was reacted with phosphorous oxychloride
and DMF to give the product as a slight yellow liquid
5.2.21. 4-Bromo-1-N,N-dibutylnaphthylamine (33).
Following the procedure described for compound 8,
4-N,N-dibutylnaphthyl-1-amine 31 (1.0 g, 3.9 mmol) in
dichloromethane (20 ml) was reacted with 2,4,4,6-tetra-
bromo-2,5-cyclohexadien-1-one (1.6 g, 3.9 mmol) to give
1
(0.7 g, 36% in two steps). H NMR (400 MHz, CDCl3):
10.15 (s, 1H), 9.29 (d, J¼8.4 Hz, 1H), 8.05 (d, J¼8.4 Hz,
1H), 7.60 (m, 2H), 7.51 (m, 1H), 3.32 (t, J¼10.4 Hz, 2H),
3.19 (t, J¼16.4 Hz, 2H), 2.95 (t, J¼12.8 Hz, 2H), 1.91
(m, 4H), 1.35 (m, 2H), 1.00 (t, J¼14.8 Hz); 13C NMR
(CDCl3): 192.1, 152.3, 140.4, 131.4, 127.8, 125.4,
125.3, 124.2, 122.8, 56.9, 47.9, 31.1, 28.1, 20.2, 18.4,
14.0; IR (cmꢂ1): 2956, 2929, 2861, 1670, 1507, 1460.
HRMS m/z calcd for C18H21NO [M+Na]: 290.1521. Found:
290.1523.
1
the brominated product as a yellow oil (1.2 g, 92%). H
NMR (400 MHz, CDCl3): 8.37 (dd, J¼9.6 Hz, 1H), 8.22
(dd, J¼8.4 Hz, 1H), 7.71 (d, J¼8.0 Hz, 1H), 7.56 (m, 2H),
7.05 (d, J¼8.0 Hz, 1H), 3.13 (t, J¼14.8 Hz, 4H), 1.49 (m,
4H), 1.31 (m, 4H), 0.87 (t, J¼14.8 Hz, 6H); 13C NMR
(CDCl3): 148.7, 134.2, 132.9, 129.4, 127.4, 127.1, 125.8,
124.7, 118.6, 116.9, 54.0, 29.2, 20.5, 14.0; IR (cmꢂ1):
2923, 2854, 1459. HRMS m/z calcd for C18H24BrN
[M+H]: 334.1170. Found: 334.1165.
5.2.26. 6-(3-Dicyanomethylen-2-cyano-5,5-dimethyl-3,5-
dihydrofuryl)-1-butyl-1,2,3,4-tetrahydrobenzo[h]quino-
line (39). Following the procedure described for compound
8, 1-butyl-1,2,3,4-tetrahydrobenzo[h]quinoline-6-carbalde-
hyde (0.1 g, 0.37 mmol) and 2-dicyanomethylen-3-cyano-
4,5,5-trimethyl-2,5-dihydrofuran (0.07 g, 0.74 mmol) were
reacted in pyridine (20 ml) to give the product as blue
crystals (0.1 g, 60%). DSC, mp: 222 ꢀC (decomposes upon
melting); UV–vis (CH2Cl2): lmax¼656 nm, 3max¼3.75ꢁ
5.2.22. 4-N,N-Dibutyl-1-naphthaldehyde (34). Following
the procedure described for compound 29, 4-bromo-N,N-di-
butylnaphthylamine 33 (1.5 g, 4.5 mmol) was reacted with
2.5 M of n-BuLi in hexane (2.5 ml, 6.3 mmol) and anhy-
drous DMF (1.7 g, 22.5 mmol) to give the product as a light
1
yellow liquid (0.7 g, 55%). H NMR (400 MHz, CDCl3):
10.23 (s, 1H), 9.32 (d, 1H), 8.23 (dd, J¼8.4, 0.8 Hz, 1H),
1
104 l cmꢂ1 molꢂ1; H NMR (300 MHz, CDCl3): 8.64 (d,
7.88 (d, J¼8.0 Hz, 1H), 7.65 (m, 1H), 7.55 (m, 1H), 7.14
J¼16.0 Hz, 1H), 8.06 (m, 2H), 7.77 (s, 1H), 7.60 (m, 1H),

H. Wang et al. / Tetrahedron 63 (2007) 103–114
113
7.50 (m, 1H), 6.97 (d, J¼15.6 Hz, 1H), 3.43 (t, J¼10.8 Hz,
2H), 3.38 (t, J¼15.6 Hz, 2H), 2.98 (t, J¼12.4 Hz, 2H),
2.04 (m, 2H), 1.87 (s, 6H), 1.39 (m, 2H), 0.99 (t,
J¼14.8 Hz, 3H); 13C NMR (DMSO): 173.8, 152.8, 143.5,
133.2, 129.3, 127.6, 127.1, 125.4, 125.0, 124.2, 122.4,
121.8, 111.3, 96.7, 57.3, 48.9, 30.9, 28.4, 26.7, 20.1, 19.7,
13.7; IR (cmꢂ1): 2932, 2867, 2218, 1485. Anal. Calcd for
C29H28N4O: C, 77.65; H, 6.29; N, 12.49. Found: C, 77.48;
H, 6.25; N, 12.78.
5.3.3. Crystal data of 30. C30H30N4O2, Mw¼
478.58 g molꢂ1, crystal dimensions 0.58ꢁ0.36ꢁ0.15 mm,
triclinic, space group P-1, a¼9.484(2), b¼10.296(3),
c¼14.516(4) A, a¼83.188(4)ꢀ, b¼73.346(4)ꢀ; g¼
˚
3
70.007(4) , V¼1275.8(6) A , Z¼2, rcalcd¼1.246 g cmꢂ3
,
ꢀ
Bruker SMART APEX II diffractometer, 2.11<q<25.05,
˚
˚
Mo Ka radiation (l¼0.71073 A), u scans, T¼100(2) K; of
10066 measured reflections, 4514 were independent and
3211 observed with I>2s(I), ꢂ11<h<11, ꢂ12<k<12,
ꢂ17<l<17; R1¼0.0413, wR2¼0.1078, GOF¼0.732 for
328 parameters, Drmax¼0.221 eAꢂ3. The structure was
˚
5.3. X-ray crystallographic data
solved by direct methods (SHELXS-97) and refined by
full-matrix least-squares procedures (SHELXL-97), Lorent-
zian and polarization corrections and absorption correction
X-ray crystallography was performed by mounting each
crystal onto a thin glass fiber from a pool of FluorolubeÔ
and immediately placing it under a liquid N2 stream, on
a Bruker AXS diffractometer. The radiation used was graph-
SADABS were applied, m¼0.079 mmꢂ1
.
˚
ite monochromatized Mo Ka radiation (l¼0.7107 A). The
Crystallographic data (excluding structural factors) for the
structures in this paper have been deposited at the Cam-
bridge Crystallographic Data Centre as supplementary
publication nos. CCDC 618492 for 16,CCDC 618493 for
17, and CCDC 623895 for 30. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033 or
e-mail: deposit@ccdc.cam.ac.uk).
lattice parameters were optimized from a least-square calcu-
lations on carefully centered reflections. Lattice determina-
tion, data collection, structure refinement, scaling, and data
reduction were carried out using APEX2 version 1.0-27 soft-
ware package. Each structure was solved using direct
methods. This procedure yielded a number of C, N, and O
atoms. Subsequent Fourier synthesis yielded the remaining
atom positions. The hydrogen atoms were fixed in positions
of ideal geometry and refined within the XSHELL software.
These idealized hydrogen atoms had their isotropic temper-
ature factors fixed at 1.2 or 1.5 times the equivalent isotropic
U of the C atoms to which they were bonded. The final
refinement of each compound included anisotropic thermal
parameters on all nonhydrogen atoms.
Acknowledgements
This work was supported by the Department of Energy Grant
No. DE FG02-04ER63777 and also by the National Insti-
tutes of Health Grant No. 5P20-HG003638-02.
5.3.1. Crystal data of 16. C22H20N4O, Mw¼
356.42 g molꢂ1, crystal dimensions 0.21ꢁ0.14ꢁ0.13 mm,
References and notes
monoclinic, space group P2(1)/c, ꢀa¼11.048(3), b¼
3
˚
˚
9.683(3), c¼17.080(5) A, b¼98.456(5) ; V¼1807.4(9) A ,
Z¼4, rcalcd¼1.310 g cmꢂ3, Bruker SMART APEX II dif-
fractometer, 1.87<q<22.78, Mo Ka radiation (l¼
1. Moerner, W. E. Trends Anal. Chem. 2003, 22, 544–548.
2. Doroshenko, A. O.; Bilokin, M. D.; Pivovarenko, V. G.
J. Photochem. Photobiol., A 2004, 163, 95–102.
3. Arunkumar, E.; Forbes, C. C.; Noll, B. C.; Smith, B. D. J. Am.
Chem. Soc. 2005, 127, 3288–3289.
4. Kovalska, V. B.; Kryvorotenko, D. V.; Balanda, A. O.;
Losytskyy, M. Y.; Tokar, V. P.; Yarmoluk, S. M. Dyes
Pigments 2005, 67, 47–54.
5. Willets, K. A.; Ostroverkhova, O.; Hess, S.; He, M.; Twieg,
R. J.; Moerner, W. E. Proc. SPIE-Int. Soc. Opt. Eng. 2003,
5222, 150–157.
6. Willets, K. A.; Ostroverkhova, O.; He, M.; Twieg, R. J.;
Moerner, W. E. J. Am. Chem. Soc. 2003, 125, 1174–1175.
7. Schuck, P. J.; Willets, K. A.; Fromm, D. P.; Twieg, R. J.;
Moerner, W. E. Chem. Phys. 2005, 318, 7–11.
8. Nishimura, S. Y.; Lord, S. J.; Klein, L. O.; Willets, K. A.; He,
M.; Lu, Z. K.; Twieg, R. J.; Moerner, W. E. J. Phys. Chem. B
2006, 110, 8151–8157.
9. Willets, K. A.; Nishimura, S. Y.; Schuck, P. J.; Twieg, R. J.;
Moerner, W. E. Acc. Chem. Res. 2005, 38, 549–556.
10. Valeur, B. Molecular Fluorescence: Principles and Applica-
tions; Wiley-VCH: Weinheim, 2002.
11. Willets, K. A.; Callis, P. R.; Moerner, W. E. J. Phys. Chem. B
2004, 108, 10465–10473.
12. Melikian, G.; Rouessac, F. P.; Alexandre, C. Synth. Commun.
1995, 25, 3045–3051.
˚
0.71073 A), u scans, T¼105(2) K; of 11176 measured re-
flections, 2442 were independent and 1430 observed with
I>2s(I), ꢂ11<h<12, ꢂ10<k<10, ꢂ18<l<18; R1¼
0.0418, wR2¼0.1041, GOF¼0.880 for 247 parameters,
Drmax¼0.213 eAꢂ3. The structure was solved by direct
˚
methods (SHELXS-97) and refined by full-matrix least-
square procedures (SHELXL-97), Lorentzian and polariza-
tion corrections and absorption correction SADABS were
applied, m¼0.083 mmꢂ1
.
5.3.2. Crystal data of 17. C25H28N4O, Mw¼
400.51 g molꢂ1, crystal dimensions 0.44ꢁ0.31ꢁ0.08 mm,
triclinic, space group P-1, a¼7.7832(12), b¼9.7606(15),
c¼14.830ꢀ(2) A, a¼78.033(3)ꢀ, b¼83.752(3)ꢀ; g¼
˚
85.128(3) , V¼1093.4(3) A , Z¼2, rcalcd¼1.217 g cmꢂ3
,
Bruker SMART APEX II diffractometer, 1.87<q<25.05,
3
˚
˚
Mo Ka radiation (l¼0.71073 A), u scans, T¼100(2) K; of
8787 measured reflections, 3854 were independent and
2241 observed with I>2s(I), ꢂ9<h<9, ꢂ11<k<11,
ꢂ17<l<17; R1¼0.0987, wR2¼0.2718, GOF¼1.834 for
247 parameters, Drmax¼0.856 eAꢂ3. The structure was
˚
solved by direct methods (SHELXS-97) and refined by
full-matrix least-square procedures (SHELXL-97), Lorent-
zian and polarization corrections and absorption correction
13. Gubler, U.; He, M.; Wright, D.; Roh, Y.; Twieg, R.; Moerner,
W. E. Adv. Mater. 2002, 14, 313–317.
SADABS were applied, m¼0.076 mmꢂ1
.

114
H. Wang et al. / Tetrahedron 63 (2007) 103–114
14. Zhang, C.; Dalton, L. R.; Oh, M. C.; Zhang, H.; Steier, W. H.
Chem. Mater. 2001, 13, 3043–3050.
25. Moerner, W. E.; Fromm, D. P. Rev. Sci. Instrum. 2003, 74,
3597–3619.
15. Zhang, C.; Wang, C. G.; Dalton, L. R.; Zhang, H.; Steier, W. H.
Macromolecules 2001, 34, 253–261.
16. You, W.; Hou, Z. J.; Yu, L. P. Adv. Mater. 2004, 16, 356.
17. Ostroverkhova, O.; He, M.; Twieg, R. J.; Moerner, W. E.
ChemPhyschem 2003, 4, 732–744.
26. Enderlein, J. Opt. Lett. 2000, 25, 634–636.
27. Soper, S. A.; Nutter, H. L.; Keller, R. A.; Davis, L. M.; Shera,
E. B. Photochem. Photobiol. 1993, 57, 972–977.
28. March, J. Advanced Organic Chemistry: Reactions, Mecha-
nisms and Structure, 4th ed.; Wiley: New York, NY, 1992.
29. Newman, M. S.; Galt, R. H. E. J. Org. Chem. 1960, 25,
214–215.
18. Jung, B. J.; Lee, J. I.; Chu, H. Y.; Do, L. M.; Lee, J.; Shim, H. K.
J. Mater. Chem. 2005, 15, 2470–2475.
19. Cai, G. L.; Bozhkova, N.; Odingo, J.; Berova, N.; Nakanishi, K.
J. Am. Chem. Soc. 1993, 115, 7192–7198.
20. Hou, Z. J.; You, W.; Yu, L. P. Appl. Phys. Lett. 2004, 85, 5221–
5223.
30. Lakowicz, J. R. Principles of Fluorescence Spectroscopy,
2nd ed.; Kluwer Academic/Plenum: New York, NY, 1999.
31. Katayama, H.; Ohkoshi, M.; Kaneko, K. Chem. Pharm. Bull.
1984, 32, 1770–1779.
21. Guinot, S. G. R.; Hepworth, J. D.; Wainwright, M. J. Chem.
Soc., Perkin Trans. 2 1998, 297–303.
22. Katayama, H.; Abe, E.; Kaneko, K. J. Heterocycl. Chem. 1982,
19, 925–926.
23. Saeki, S. Chem. Pharm. Bull. 1961, 9, 226–233.
24. Lobo, B. C.; Abelt, C. J. J. Phys. Chem. A 2003, 107, 10938–
10943.
32. Sanguinet, L.; Twieg, R. J.; Wiggers, G.; Mao, G. L.; Singer,
K. D.; Petschek, R. G. Tetrahedron Lett. 2005, 46, 5121–
5125.
33. Picard, J. P.; Azizelyusufi, A.; Calas, R.; Dunogues, J.; Duffaut,
N. Organometallics 1984, 11, 1660–1665.
34. Voronin, M. V.; Nasibulin, A. A.; Klyuyev, M. V. Pet. Chem.
USSR 1997, 6, 508–514.