Reactions of azulenes with 1,2-diaryl-1,2-ethanediols in methanol in the presence of hydrochloric acid: Comparative studies on products, crystal structures, and spectroscopic and electrochemical properties

Article abstract of DOI:10.1016/j.tet.2004.05.022

Although reaction of guaiazulene (1a) with 1,2-diphenyl-1,2-ethanediol (2a) in methanol in the presence of hydrochloric acid at 60°C for 3 h under aerobic conditions gives no product, reaction of 1a with 1,2-bis(4- methoxyphenyl)-1,2-ethanediol (2b) under the same reaction conditions as 2a gives a new ethylene derivative, 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl) ethylene (3), in 97% yield. Similarly, reaction of methyl azulene-1-carboxylate (1b) with 2b under the same reaction conditions as 1a gives no product; however, reactions of 1-chloroazulene (1c) and the parent azulene (1d) with 2b under the same reaction conditions as 1a give 2-[3-(1-chloroazulenyl)]-1,1-bis(4- methoxyphenyl)ethylene (4) (81% yield) and 2-azulenyl-1,1-bis(4-methoxyphenyl) ethylene (5) (15% yield), respectively. Along with the above reactions, reactions of 1a with 1,2-bis(4-hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-ethanediol (2d) under the same reaction conditions as 2b give 2-(3-guaiazulenyl)-1,1-bis(4-hydroxyphenyl)ethylene (6) (73% yield) and (Z)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1- phenylethylene (7) (17% yield), respectively. Comparative studies of the above reaction products and their yields, crystal structures, spectroscopic and electrochemical properties are reported and, further, a plausible reaction pathway for the formation of the products 3-7 is described.

Full text of DOI:10.1016/j.tet.2004.05.022

Tetrahedron 60 (2004) 5983–6000
Reactions of azulenes with 1,2-diaryl-1,2-ethanediols in methanol
in the presence of hydrochloric acid: comparative studies on
products, crystal structures, and spectroscopic and
electrochemical properties
Miwa Nakatsuji,a Yasuhito Hata,a Takeshi Fujihara,a Kensaku Yamamoto,a Masato Sasaki,a
Hideko Takekuma,a Masakuni Yoshihara,a Toshie Minematsub and Shin-ichi Takekumaa
,
*
aDepartment of Applied Chemistry, Faculty of Science and Engineering, Kinki University, 3-4-1 Kowakae, Higashi-Osaka-shi,
Osaka 577-8502, Japan
bSchool of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka-shi, Osaka 577-8502, Japan
Received 16 March 2004; accepted 10 May 2004
Available online 8 June 2004
Abstract—Although reaction of guaiazulene (1a) with 1,2-diphenyl-1,2-ethanediol (2a) in methanol in the presence of hydrochloric acid at
60 8C for 3 h under aerobic conditions gives no product, reaction of 1a with 1,2-bis(4-methoxyphenyl)-1,2-ethanediol (2b) under the same
reaction conditions as 2a gives a new ethylene derivative, 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3), in 97% yield. Similarly,
reaction of methyl azulene-1-carboxylate (1b) with 2b under the same reaction conditions as 1a gives no product; however, reactions of
1-chloroazulene (1c) and the parent azulene (1d) with 2b under the same reaction conditions as 1a give 2-[3-(1-chloroazulenyl)]-1,1-bis(4-
methoxyphenyl)ethylene (4) (81% yield) and 2-azulenyl-1,1-bis(4-methoxyphenyl)ethylene (5) (15% yield), respectively. Along with the
above reactions, reactions of 1a with 1,2-bis(4-hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-
ethanediol (2d) under the same reaction conditions as 2b give 2-(3-guaiazulenyl)-1,1-bis(4-hydroxyphenyl)ethylene (6) (73% yield) and (Z)-
2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7) (17% yield), respectively. Comparative studies of the above reaction
products and their yields, crystal structures, spectroscopic and electrochemical properties are reported and, further, a plausible reaction
pathway for the formation of the products 3–7 is described.
q 2004 Elsevier Ltd. All rights reserved.
Azulenes have become readily available by synthesis over
the past 40 years and aroused considerable interest as a
representative example of non-benzenoid aromatic hydro-
carbons, because of their facile electrophilic substitution
reactions and insusceptibility to Diels–Alder-type addition
reactions.
(1a) with the corresponding aldehyde compounds in acetic
acid (and methanol) in the presence of hexafluoro-
phosphoric acid (and tetrafluoroboric acid), respectively.1–7
During the course of our investigations, we have quite
recently found that the reaction of 1a with 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b) in methanol in the
presence of hydrochloric acid at 60 8C for 3 h gave a new
ethylene derivative, 2-(3-guaiazulenyl)-1,1-bis(4-methoxy-
phenyl)ethylene (3) (97% yield) and, further, have found
that the reduction of a,a0-bis(3-guaiazulenylmethylium)
bis(tetrafluoroborate) (8), whose carbonium ion is known,8,9
with zinc powder in trifluoroacetic acid at 0 8C for 5 min
afforded (E)-1,2-di(3-guaiazulenyl)ethylene (9), efficiently
(94% yield), which enabled us to compare the spectroscopic
properties, crystal structures and electrochemical behavior
of 3 under the same analytical conditions as 9. Although 9 is
also a known compound,10–12 which was prepared, in 72%
yield, by the McMurry reaction of guaiazulene-3-carbalde-
As a series of basic studies on the creation of novel
functional materials with a delocalized p-electron system
and their potential utility, we have been working on a facile
preparation, the molecular and crystal structures, spectro-
scopic and characteristic chemical properties and, further,
electrochemical behavior of mono- and dicarbocations
stabilized by a 3-guaiazulenyl group for the past several
years. These products can be readily obtained by the
condensation reactions of naturally occurring guaiazulene
Keywords: Azulenes; Carbonium ions; Electrochemistry; Electron donors;
Reduction; X-ray crystal structures.
1
hyde, and the spectroscopic (UV–vis and H NMR) and
electrochemical properties of 9 were reported, nothing has
really been documented regarding other spectroscopic
*
Corresponding author. Tel.: þ81-6-6730-5880x4020; fax: þ81-6-6727-
4301; e-mail address: takekuma@apch.kindai.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.022

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M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
properties (i.e. IR, MS and 13C NMR) and the X-ray crystal
structure of 9. Now, our interest has been focused on a
comparative study of the reactions of guaiazulene (1a),
methyl azulene-1-carboxylate (1b), 1-chloroazulene (1c)
and the parent azulene (1d) with 1,2-bis(4-methoxyphenyl)-
1,2-ethanediol (2b) in methanol in the presence of
hydrochloric acid at 60 8C for 3 h along with the reactions
of 1a with 1,2-diphenyl-1,2-ethanediol (2a), 1,2-bis(4-
hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-(dimethyl-
amino)phenyl]-2-phenyl-1,2-ethanediol (2d) under the
same reaction conditions as 2b. We now wish to report
our detailed studies on the molecular structures of the above
reaction products and their yields and, further, their
spectroscopic properties, crystal structures and electro-
chemical behavior compared with those of 9.
bands of 3 resembled that of 9, the longest absorption
wavelength of 3 (lmax 635 nm, log 1¼2.54) showed a
hypsochromic shift (D 26 nm) and a hypochromic effect in
comparison with that of 9 (lmax 661 nm, log 1¼3.13). The
IR (KBr) spectrum showed four specific bands based on the
C–O at nmax 1242 and 1034 cm21, and the aromatic CvC
at nmax 1605 and 1508 cm21. The MALDI-TOF-MS
(without any matrix reagent) spectrum showed only a
molecular ion peak at m/z 436 (Mþ, 100%). The molecular
formula C31H32O2 was determined by the exact EI-MS
(70 eV) spectrum. The elemental analysis confirmed the
molecular formula C31H32O2. The 1H NMR (C6D6)
spectrum showed signals based on the 3-guaiazulenyl
group, signals based on the two 4-methoxyphenyl groups
which were not equivalent, and a signal based on the
.CvCH– unit, whose signals were carefully assigned
1. Results and discussion
1.1. Reaction of guaiazulene (1a) with 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b): an efficient
preparation and spectroscopic properties of 2-(3-
guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3)
Compound 3 was prepared using a methanol as a solvent as
shown in Section 3.1.2, whose molecular structure was
established on the basis of elemental analysis and spectro-
scopic data [UV–vis, IR, MALDI-TOF- and EI-MS, 1H and
13C NMR including 2D NMR (i.e. H–H COSY, NOESY,
HMQC¼1H detected heteronuclear multiple quantum
coherence and HMBC¼1H detected heteronuclear multiple
bond connectivity)].
Compound 3 (97% yield) was dark-green needles [mp
150 8C, determined by thermal analysis (TGA and DTA)].
The UV–vis [lmax (CH3CN) nm] spectrum is shown in
Figure 1(a). A comparative study of the UV–vis spectrum
of 3 with those of guaiazulene (1a)13 and (E)-1,2-di(3-
guaiazulenyl)ethylene (9) (see Section 3.1.17) showed that:
(i) similarly, as in the case of 9 [see Fig. 1(b)], no
characteristic UV–vis absorption bands for guaiazulene
were observed, indicating the formation of the molecule 3
with a delocalized p-electron system; and (ii) although the
spectral pattern of the characteristic UV–vis absorption
Figure 1. The UV–vis spectra of 3 (a) and 9 (b) in CH3CN. Concentrations,
3: 0.010 g/L (22.9 mmol/L), 9: 0.012 g/L (28.5 mmol/L). Length of the cell,
1 cm each.

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5985
using the computer-assisted simulation analysis, H–H
COSY and NOESY techniques. The proton signals of the
Me-1000 (d 2.31) and H-2000 (7.44) of the 3-guaiazulenyl group
and the .CvCH– (7.77) unit for 3 showed apparent up-
field shifts0i0 n comparison with those [i.e. the Me-10,100 (2.57)
and H-20,2 (8.14) of the two 3-guaiazulenyl groups and the
–HCvCH– (8.12 equiv.) unit] of 9. The 13C NMR (C6D6)
spectrum exhibited twenty-six carbon signals assigned by
HMQC and HMBC techniques. Although the carbon signal
of the .CvCH–(d125.6) unit of 3 coincided with those of
the –HCvCH– (125.2 equiv.) unit of 9, the carbon signals
of the C-2000 (140.4), C-3a000 (135.5) and C-3000 (127.2) of the
3-guaiazulenyl group for 3 showed apparent down- and
up-field shifts in00 comparison with0 those [i.e. the C-20,200
(136.1), C-3a0,3a (132.5) and C-3 ,300 (128.8) of the two
3-guaiazulenyl groups] of 9. From a comparative study of
the chemical shifts (d, ppm) for the proton and carbon
signals of 3 with those of 113 and 9, it can be inferred that:
(i) although the planes of the two 3-guaiazulenyl groups for
9 are co-planar with that of the –HCvCH– unit, forming
the molecule 9 with a delocalized p-electron system, the
plane of the 3-guaiazulenyl group for 3 twists from that of
the .CvCH– unit owing to the influence of steric
hindrance and repulsion between the 3-guaiazulenyl group
and the (Z)-4-methoxyphenyl group; however, (ii) the
molecule 3 with a delocalized p-electron system is
apparently formed in an organic solvent (e.g. acetonitrile
or benzene). The elemental analysis and these spectroscopic
data for 3 led to the molecular structure, 2-(3-guaiazulenyl)-
1,1-bis(4-methoxyphenyl)ethylene.
1.2. X-ray crystal structure of 2-(3-guaiazulenyl)-1,1-
bis(4-methoxyphenyl)ethylene (3) compared with those
of (E)-1,2-di(3-guaiazulenyl)ethylene (9), trans-stilbene
(10) and (Z)-1-chloro-2-(4-methylphenyl)-1,2-
diphenylethylene (11)
The crystal structure of compound 3 was then determined by
means of X-ray diffraction, producing accurate structural
parameters. The ORTEP drawing of 3, indicating the
Figure 2. The ORTEP drawings with the numbering scheme (30% probability thermal ellipsoids) of 3 (a) and 9 (c) and the packing structures of 3 (b) and 9 (d);
0
0
0
˚
hydrogen atoms are omitted for reasons of clarity, respectively. The bond distances (A) of 3 are as follows: C1–C2; 1.343(4), C1–C1 ; 1.487(4), C1 –C2 ;
1.390(4), C20 –C30; 1.377(5), C30 –C40; 1.377(5), C40 –C50; 1.377(5), C50 –C60; 1.382(5), C60 –C10; 1.390(5), C40 –O1; 1.373(4), O1–CH3; 1.397(6), C1–C100;
1.486(4), C100 –C200; 1.394(4), C200 –C300; 1.373(5), C300 –C400; 1.374(4), C400 –C500; 1.376(4), C500 –C600; 1.380(4), C600 –C100; 1.382(4), C400 –O2; 1.375(4), O2–
CH3; 1.415(5), C1000 –C2000; 1.382(5), C2000 –C3000; 1.407(5), C3000 –C3a000; 1.416(5), C3a000 –C4000; 1.393(4), C4000 –C5000; 1.390(5), C5000 –C6000; 1.388(5), C6000 –C7000;
1.383(4), C7000 –C8000; 0100.384(5), C8000 –C8a000; 1.382(4), C8a000 –C1000; 1.413(5), C3a000 –C8a000; 1.515(4), C1000 –C9000; 1.507(5), C4000 –C10000; 1.508(5), C7000 –0C11000;
000
000
000
000
0
˚
1.528(5), C11 –C12 ; 1.511(6), C11 0 –C13 ; 1.516(6) and C2–C3 ; 1.464(4). The bond distan0ces (A) of 9 are a0s follows: C1–C2; 1.32(1), C1 –C2 ;
1.378(8), C20 –C30; 1.452(8), C30 –C3a ; 1.391(7), C3a0 –C40; 1.404(8), C40 –C50; 1.369(9), C50 –C6 ; 1.40(1), C60 –C7 ; 1.362(10), C70 –C80; 1.397(9), C80 –
C8a0; 1.351(8), C8a0 –C10; 1.388(8), C3a0 –C8a0; 1.533(8), C10 –C90; 1.509(9), C40 –C100; 1.512(9), C70 –C110; 1.561(10), C110 –C120 1.43(1), C110 –C130;
1.52(1) and C1–C30; 1.444(8).

5986
M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
molecular structure, 2-(3-guaiazulenyl)-1,1-bis(4-methoxy-
phenyl)ethylene, compared with that of (E)-1,2-di(3-
guaiazulenyl)ethylene (9) is shown in Figure 2(a) together
with the selected bond distances. As the result, the structural
parameters of 3 revealed that: (i) the C–C bond distance
(50) (41% yield), showing a very complicated 1H NMR
spectrum. The structures of the products 50 were presumed
on the basis of elemental analysis and spectroscopic data (IR
and EI-MS) (see Section 3.1.8).
˚
between the .CvCH– unit [1.343(4) A] was character-
istically longer than those of the –HCvCH– units of 9
14
˚
˚
[1.32(1) A] and trans-stilbene (10) [1.326(2) A];
however, the C–C bond distance between the .CvCH–
unit coincided with that of the .CvCCl– unit of (Z)-1-
chloro-2-(4-methylphenyl)-1,2-diphenylethylene (11)
15
˚
[1.340(3) A]; (ii) although the crystal structure of 9 was
planar from the dihedral angles between the least-squares
planes, the planes of the two 40- and 400-methoxyphenyl and
3000-guaiazulenyl groups of 3 twisted by 51.58, 136.98 and
47.48 from that of the .CvCH– unit, respectively, owing
to the influence of large steric hindrance and repulsion
between those three groups; (iii) the average C–C bond
distances for the seven- and five-membered rings of the 3000-
1.4. X-ray crystal structure of 2-[3-(1-chloroazulenyl)]-
1,1-bis(4-methoxyphenyl)ethylene (4) compared with
that of 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)-
ethylene (3)
˚
guaiazulenyl group (1.405 and 1.427 A) coincided with the
Although an X-ray crystallographic analysis of compound 5
has not yet been achieved because of difficulty in obtaining
a single crystal suitable for this purpose, the crystal structure
of compound 4 has been determined. The ORTEP drawing
of 4, indicating the molecular structure, 2-[3-(1-chloro-
azulenyl)]-1,1-bis(4-methoxyphenyl)ethylene, is shown in
Figure 3(a) together with the selected bond distances. As the
result, the structural parameters of 4 revealed that: (i) the
C–C bond distance between the .CvCH– unit
bond distances observed for those of the 30- and 300-
˚
guaiazulenyl groups of 9 (1.403 and 1.429 A each); and (iv)
the average C0–0 C bond distances for the benzene rings of the
coincided with the bond distances observed for those of the
0
˚
two 4 - and 4 -methoxyphenyl groups (1.382 and 1.380 A)
14
˚
two benzene rings of 10 (1.386 A each). Along with the
crystal structures of 3 and 9 [see Fig. 2(a) and (c)],
the packing structures of 3 and 9 revealed that: although the
molecule 3 did not form a p-stacking structure in the single
crystal as shown in Figure 2(b), the molecule 9 formed a
p-stacking structure in the single crystal as shown in
Figure 2(d), whose average inter-plane distance between the
˚
[1.347(3) A] coincided with that of the .CvCH– unit of
˚
3 [1.343(4) A]; (ii) similarly, as in the case of 3 [see
Fig. 2(a)], the planes of the two 40- and 400-methoxyphenyl
and 3000-(1-chloroazulenyl) groups of 4 twisted by 70.98,
30.88 and 16.48 from that of the .CvCH– unit,
respectively, owing to the influence of large steric hindrance
and repulsion between those three groups; (iii) the average
C–C bond distances for the seven- and five-membered rings
˚
over-lapping molecules was 3.82 A. Thus, the reason why
the yield of 9 as single crystals was high (94% yield) can be
inferred to be that 9 readily forms an accumulation (i.e. an
inter-molecular p-stacking structure) in the recrystallization
solvent, providing the single crystals of 9 efficiently.
000
˚
of the 3 -(1-chloroazulenyl) group (1.400 and 1.417 A)
coincided with the bond distances observed for those of the
000
˚
3 -guaiazulenyl group of 3 (1.405 and 1.427 A); and (iv)
1.3. A comparative study of the reactions of methyl
azulene-1-carboxylate (1b), 1-chloroazulene (1c) and the
parent azulene (1d) with 1,2-bis(4-methoxyphenyl)-1,2-
ethanediol (2b) under the same conditions as the reaction
of guaiazulene (1a) with 2b
the average C0–0 C bond distances for the benzene rings of the
0
˚
two 4 - and 4 -methoxyphenyl groups (1.382 and 1.386 A)
coincided with 0t0he bond distances observed for those of the
two 40- and 4 -methoxyphenyl groups of 3 (1.382 and
˚
1.380 A). Along with the crystal structure of 4, the packing
The reactions of methyl azulene-1-carboxylate (1b),
1-chloroazulene (1c) and the parent azulene (1d) with 2b
under the same reaction conditions as 1a (see Section 3.1.2)
were investigated. As the result, it was found that: although
the reaction of 1b with 2b gave no product (see Section
3.1.4), the reactions of 1c and 1d with 2b afforded 2-[3-(1-
chloroazulenyl)]-1,1-bis(4-methoxyphenyl)ethylene (4)
(81% yield) and 2-azulenyl-1,1-bis(4-methoxyphenyl)-
ethylene (5) (15% yield), respectively, whose molecular
structures were established on the basis of elemental
structure of 4 revealed that: although the molecule 3 did not
form a p-stacking structure in the single crystal as shown in
Figure 2(b), the molecule 4 formed a p-stacking structure in
the single crystal as shown in Figure 3(b), whose average
inter-plane distance between the over-lapping molecules
˚
was 4.04 A.
1.5. A comparative study of the reactions of guaiazulene
(1a) with 1,2-diphenyl-1,2-ethanediol (2a), 1,2-bis(4-
hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-(dimethyl-
amino)phenyl]-2-phenyl-1,2-ethanediol (2d) under the
same conditions as the reaction of 1a with 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b)
1
analysis and spectroscopic data [UV–vis, IR, EI-MS, H
and 13C NMR including 2D NMR (i.e. H–H COSY,
NOESY, HMQC and HMBC)] (see Sections 3.1.6 for 4;
3.1.8 for 5). Similarly, as in the case of 2-(3-guaiazulenyl)-
1,1-bis(4-methoxyphenyl)ethylene (3), the 1H NMR signals
of 4 and 5 were carefully assigned using the computer-
assisted simulation analysis. Furthermore, the reaction of 1d
with 2b gave, besides 5, a chromatographically inseparable
mixture of several bis[bis(4-methoxyphenyl)vinyl]azulenes
The reactions of 1a with 1,2-diphenyl-1,2-ethanediol (2a),
1,2-bis(4-hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-
(dimethylamino)phenyl]-2-phenyl-1,2-ethanediol (2d)
under the same conditions as the reaction of 1a with 2b
(see Section 3.1.2) were investigated. As the result, it was

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5987
Figure 3. The ORTEP drawing (a) with the numbering scheme (30% probability thermal ellipsoids) of 4 0and the packin0g structure (b) of 4;0hydrogen atoms
0
0
˚
are omitted for reasons of clarity. The bond distances (A) of 4 are as follows: C1–C2; 1.347(3), C1–C1 ; 1.498(3), C1 –C2 ; 1.376(3), C2 –C3 ; 1.382(3),
C30 –C40; 1.381(3), C40 –C50; 1.383(3), C50 –C60; 1.375(3), C60 –C10 1.395(3), C40 –O1; 1.370(3), O1–CH3; 1.423(3), C1–C100; 1.486(3), C100 –C200; 1.385(3),
C200 –C300; 1.384(4), C300 –C400; 1.390(4), C400 –C500; 1.379(3), C500 –C600; 1.375(3), C600 –C100; 1.398(3), C400 –O2; 1.366(3), O2–CH3; 1.393(3), C1000 –C2000;
1.377(4), C2000 –C3000; 1.412(3), C3000 –C3a000; 1.413(3), C3a000 –C4000; 1.387(3), C4000 –C5000; 1.388(4), C5000 –C6000; 1.392(4), C6000 –C7000; 1.373(4), C7000 –C8000;
1.390(4), C8000 –C8a000; 1.378(4), C8a000 –C1000; 1.393(4), C3a000 –C8a000; 1.487(3), C1000 –Cl; 1.732(3) and C2–C3000; 1.448(3).
found that: although the reaction of 1a with 2a gave no
product (see Section 3.1.10), the reactions of 1a with 2c and
2d afforded 2-(3-guaiazulenyl)-1,1-bis(4-hydroxyphenyl)-
ethylene (6) (73% yield) and (Z)-2-[4-(dimethylamino)-
phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7) (17%
yield), respectively, whose molecular structures were
established on the basis of elemental analysis and spectro-
of the 4000-(dimethylamino)phenyl, 30-guaiazulenyl and
phenyl groups of 7 twisted by 153.48, 82.68 and 22.18
from that of the –HCvCr unit, respectively, owing to the
influence of large steric hindrance and repulsion between
those three groups; (iii) the average C–C bond distances for
the seven- and five-membered rings of the 30-guaiazulenyl
˚
group (1.409 and 1.420 A) coincided with the bond
scopic data [UV–vis, IR, EI- and FAB-MS, H and 13C
distances observed for those of the 3000-guaiazulenyl group
1
˚
of 3 (1.405 and 1.427 A); (iv) the average C–C bond
NMR including 2D NMR (i.e. H–H COSY, NOESY,
HMQC and HMBC)] (see Sections 3.1.12 for 6; 3.1.14 for
7). Similarly, as in the case of 2-(3-guaiazulenyl)-1,1-bis(4-
methoxyphenyl)ethylene (3), the 1H NMR signals of 6 and 7
were carefully assigned using the computer-assisted
simulation analysis.
˚
distance for the benzene ring of the C-1 position (1.382 A)
coincided with the bond distances observed for those of the
14
˚
two benzene rings of trans-stilbene (10) (1.386 A each);
and (v) the plane of the dimethylamino group was co-planar
with that of the benzene ring0o00f the C-2 position and, further,
although the C4000 –N and C1 –C2 bond distances [1.382(3)
˚
and 1.463(4) A] were longer than the C4–N and C1–Ca
˚
bond distances [1.359(7) and 1.414(7) A] of [4-(dimethyl-
amino)phenyl]-3-guaiazulenylmethylium tetrafluoroborate
(12)5 with the resonance forms of the 3-guaiazulenylium
120 and quinonoid 1200 structures in the single crystal, the
dimethylaminobenzene ring clearly indicated the bond
alternation between the single and double bonds, which
coincided with the bond alternation pattern observed for the
dimethylaminobenzene ring of 12, in comparison with the
benzene ring of the C-1 position. Along with the crystal
structure of 7, the packing structure of 7 revealed that:
similarly, as in the case of 3, the molecule 7 did not form a
p-stacking structure in the single crystal as shown in
Figure 4(b). A comparative study of the C–C bond
distances for the partial structures (i.e. azulenylethylene
units) of 3, 4, 7 and 9 is shown in Table 1.
1.6. X-ray crystal structure of (Z)-2-[4-(dimethyl-
amino)phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7)
compared with those of 2-(3-guaiazulenyl)-1,1-bis(4-
methoxyphenyl)ethylene (3), trans-stilbene (10) and [4-
(dimethylamino)phenyl]-3-guaiazulenylmethylium
tetrafluoroborate (12)
1.7. A plausible reaction pathway for the formation of 2-
(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3),
2-[3-(1-chloroazulenyl)]-1,1-bis(4-methoxyphenyl)-
ethylene (4), 2-azulenyl-1,1-bis(4-methoxyphenyl)-
ethylene (5) and 2-(3-guaiazulenyl)-1,1-bis(4-hydroxy-
phenyl)ethylene (6)
The crystal structure of compound 7, indicating the
molecular structure, (Z)-2-[4-(dimethylamino)phenyl]-1-
(3-guaiazulenyl)-1-phenylethylene, is shown in Figure 4(a)
together with the selected bond distances. As the result, the
structural parameters of 7 revealed that: (i) the C–C bond
distance between the –HCvCr unit [1.347(4) A] coincided
˚
with that of the .CvCH– unit of 3 [1.343(4) A];
(ii) similarly, as in the case of 3 [see Fig. 2(a)], the planes
˚
In 1932 Bachmann and Moser reported the pinacol–

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M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
Figure 4. The ORTEP drawing (a) with the numbering scheme (30% probability thermal ellipsoids) of 0700 and the packing stru0c00ture (b) of 7; hydrogen atoms are
000
000
000
˚
omitted for reasons of clarity. The bond distances (A) of 7 are as follows: C1–C2; 1.347(4), C2–C1 ; 1.463(4), C1 –C2 ; 1.395(4), C2 –C3 ; 1.372(4),
C3000 –C4000; 1.389(4), C4000 –C5000; 1.394(4), C5000 –C6000; 1.364(4), C6000 –C1000; 1.392(4), C4000 –N; 1.382(3), N–C7000; 1.427(4), N–C8000; 1.438(4), C10 –C20;
1.373(4), C20 –C30; 1.420(4), C30 –C3a0; 1.404(4), C3a0 –C40; 1.410(4), C40 –C50; 1.382(4), C50 –C60; 1.399(4), C60 –C70; 1.386(5), C70 –C80; 1.384(4), C80 –
C8a0; 1.394(4), C8a0 –C10; 1.397(4), C3a0 –C8a0; 1.502(4), C1–C30; 1.489(4), C1–C100; 1.487(4), C100 –C200; 1.387(4), C200 –C300; 1.382(4), C300 –C400; 1.367(5),
C400 –C500; 1.381(5), C500 –C600; 1.379(4) and C600 –C100; 1.395(4).
pinacolone rearrangement; namely, on the relative
migratory aptitudes of aryl groups, and concluded that the
migration (%) of the p-anisyl (p-CH3OC6H4–) group was
extremely high.16 From this result, a plausible reaction
pathway for the formation of compound 3 can be inferred as
shown in Scheme 1: (i) upon heating 1,2-bis(4-methoxy-
phenyl)-1,2-ethanediol (2b) in methanol in the presence of
hydrochloric acid at 60 8C under aerobic conditions, it is
˚
Table 1. The C–C bond distances (A) for the azulenylethylene units of 3, 4, 7 and 9
Atom
Compound
3
4
7
9
C1–C2
1.343(4)
1.464(4)
1.382(5)
1.407(5)
1.416(5)
1.393(4)
1.390(5)
1.388(5)
1.383(4)
1.384(5)
1.382(4)
1.413(5)
1.515(4)
1.347(3)
1.448(3)
1.377(4)
1.412(3)
1.413(3)
1.387(3)
1.388(4)
1.392(4)
1.373(4)
1.390(4)
1.378(4)
1.393(4)
1.487(3)
1.347(4)
1.487(4)
1.373(4)
1.420(4)
1.404(4)
1.410(4)
1.382(4)
1.399(4)
1.386(5)
1.384(4)
1.394(4)
1.397(4)
1.502(4)
1.32(1)
C20–C300
1.444(8)
1.378(8)
1.452(8)
1.391(7)
1.404(8)
1.369(9)
1.40(1)
1.362(10)
1.397(9)
1.351(8)
1.388(8)
1.533(8)
C1 –C2
C20 –C30
C30 –C3a0
C3a0 –C40
C40 –C50
C50 –C60
C60 –C70
C70 –C80
C80 –C8a0
C8a0 –C10
C8a0 –C3a0

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5989
Scheme 1. A plausible reaction pathway for the formation of 3 from the reaction of guaiazulene (1a) with 1,2-bis(4-methoxyphenyl)-1,2-ethanediol (2b) in
methanol in the presence of hydrochloric acid at 60 8C for 3 h under aerobic conditions.
gradually converted into the pinacol rearrangement product
b via a; and, further, (ii) the reaction of guaiazulene (1a)
with the carbocation b generated under the reaction
conditions rapidly affords 3 presumably via c, d and e. A
plausible reaction pathway for the formation of the products
4–6 can be inferred to be the same as that for 3 (see
Scheme 1).
[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1-phenyl-
ethylene (7), obtained by the reaction of guaiazulene (1a)
with 1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-ethanediol
(2d), a plausible reaction pathway for the formation of
compound 7 can be inferred as shown in Scheme 2: (i)
upon heating 2d in methanol in the presence of
hydrochloric acid at 60 8C under aerobic conditions, it
is gradually converted into the dehydration product b,
simultaneously possessing a protonated amino group at
the C-40 position, via a; and, further, (ii) the reaction of
1.8. A plausible reaction pathway for the formation of
(Z)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1-
phenylethylene (7)
1a with the carbocation
b generated under the
reaction conditions rapidly affords 7 presumably via c,
d and e.
From the molecular structure of the resulting product, (Z)-2-
Scheme 2. A plausible reaction pathway for the formation of 7 from the reaction of guaiazulene (1a) with 1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-
ethanediol (2d) in methanol in the presence of hydrochloric acid at 60 8C for 3 h under aerobic conditions.

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M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
Figure 5. Cyclic and differential pulse voltammograms of 3 (3.0 mg, 6.9 mmol) (a, b) and 9 (2.0 mg, 4.8 mmol) (c, d) in 0.1 M [n-Bu4N]BF4, CH3CN (10 mL)
at a glassy carbon (ID: 3 mm) and platinum wire served as the working and auxiliary electrodes; scan rates 100 mV s21 at 25 8C under argon, respectively. For
comparative purposes, the oxidation potential using ferrocene as a standard material showed þ0.45 (Ep) V by DPV and þ0.42 (E1/2) V by CV under the same
electrochemical conditions as 3 and 9.
1.9. Electrochemical behavior of 2-(3-guaiazulenyl)-1,1-
bis(4-methoxyphenyl)ethylene (3) compared with that of
(E)-1,2-di(3-guaiazulenyl)ethylene (9)
redox potentials observed by DPV were positioned at the Ep
valuesofþ0.76, þ0.55and 21.70 V, whilethe corresponding
three reversible redox potentials determined by CV were
located at the values of þ0.73 (E1/2), þ0.52 (E1/2) and 21.73
(E1/2) V as shown in Figure 5(a) and (b). From a comparative
study of the redox potentials of 3 with those of 9 [see Fig. 5(c)
and (d)] under the same electrochemical conditions as 3, a
plausibleelectrontransfermechanismof3and9basedontheir
CV and DPV data can be inferred as shown in Schemes 3 (for
We have been interested further in a comparative study of
the electrochemical properties of compound 3 and (E)-1,2-
di(3-guaiazulenyl)ethylene (9). The electrochemical behavior
of 3 was, therefore, measured by means of CV and DPV
(Potential/V vs. SCE) in 0.1 M [n-Bu4N]BF4, CH3CN. Three
Scheme 3. A plausible electron transfer mechanism based on the CV and DPV data of 3.

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5991
Scheme 4. A plausible electron transfer mechanism based on the CV and DPV data of 9.
3) and 4 (for 9); namely, (i) 3 stepwise undergoes two-electron
oxidation at the potentials of þ0.52 (E1/2) and þ0.73 (E1/2) V
by CV (corresponding to þ0.55 and þ0.76 V by DPV),
generating an electrochemically stable dication 3b0 via the
cation-radical 3a and its resonance form 3a0 (and/or via 3a and
the resonance form 3b of the dication 3b0). Similarly, as in the
case of 3, 9 stepwise undergoes two-electron oxidation at the
potentials of þ0.20 (E1/2) and þ0.35 (E1/2) V by CV
(corresponding to þ0.24 and þ0.39 V by DPV), generating
an electrochemically stable dication 9b0 via the cation-radical
9a and its resonance form 9a0 (and/or via 9a and the resonance
form 9b of the dication 9b0). Thus, 3 is less susceptible to
oxidation than 9; (ii) 3 is reduced to the anion-radical 3c at the
potential of 21.73 (E1/2) V by CV (corresponding to 21.70 V
by DPV). Thus, the one-electron reduction potential of 3
coincideswiththat of9 [21.71(E1/2) V byCV(corresponding
to 21.66 V by DPV)]; and, further, (iii) 9 is stepwise reduced
to the dianion 9d at the potential of 21.89 (E1/2) V by CV
(corresponding to 21.85 V by DPV) via the anion-radical 9c
at the potential of 21.71 (E1/2) V by CV (corresponding to
21.66 V by DPV). As the result, the CV and DPV data
indicated 3 and 9 serve as an electron donor, respectively.
Along with the cation-radicals and the dications generated
from 3 and 9, the anion-radicals 3c, 9c and the dianion 9d are
also electrochemically stable.
[see Fig. 5(a) and (b)]. As the result, it was found that (i) 4
stepwise undergoes two-electron oxidation at the potentials
of þ0.77 (E1/2) and þ0.88 (E1/2) V by CV (corresponding to
þ0.78 and þ0.91 V by DPV), generating an electro-
chemically stable dication via an electrochemically stable
cation-radical and, further, 4 is reduced to the anion-radical
1.10. A comparative study of the electrochemical
behavior of 2-[3-(1-chloroazulenyl)]-1,1-bis(4-
methoxyphenyl)ethylene (4), 2-azulenyl-1,1-bis(4-
methoxyphenyl)ethylene (5) and 2-(3-guaiazulenyl)-1,1-
bis(4-hydroxyphenyl)ethylene (6) with that of 2-(3-guai-
azulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3)
The electrochemical behavior of compounds 4, 5 and 6 was
measured under the same electrochemical conditions as 3
Figure 6. Cyclic (a) and differential pulse (b) voltammograms of 7 (3.0 mg,
7.1 mmol) under the same electrochemical conditions as 3 and 9.

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M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
Scheme 5. A plausible electron transfer mechanism based on the CV and DPV data of 7.
at the potential of 21.32 (E1/2) V by CV (corresponding to
21.31 V by DPV), generating an electrochemically stable
anion-radical. Thus, although 4 is less susceptible to
oxidation than 3, 4 is more susceptible to reduction than
3; (ii) 5 stepwise undergoes three-electron oxidation at the
potentials of þ0.69 (Epa, irreversible; Epc: þ0.47 V), þ0.77
(E1/2) and þ0.98 (E1/2) V by CV (corresponding to þ0.55,
þ0.69, þ0.80 and þ1.00 V by DPV), generating an
electrochemically stable trication-radical via an electro-
chemically unstable cation-radical and an electrochemically
stable dication and, further, 5 is reduced to the anion-radical
at the potential of 21.53 (E1/2) V by CV (corresponding to
21.51 V by DPV), generating an electrochemically stable
anion-radical. Thus, although 5 is less susceptible to
oxidation than 3, 5 stepwise undergoes three-electron
oxidation and, further, 5 is more susceptible to reduction
than 3; and (iii) 6 stepwise undergoes two-electron oxidation
at the potentials of þ0.50 (E1/2) and þ0.70 (E1/2) V by CV
(correspondingto þ0.53and þ0.72 V byDPV), generatingan
electrochemically stable dication via an electrochemically
stable cation-radical and, further, 6 is reduced to the anion-
radical at the potential of 21.78 (Epc, irreversible) V by CV
(corresponding to 21.77 V by DPV), generating an electro-
chemically unstable anion-radical. Thus, the two-electron
oxidation potentials of 6 coincide with those of 3. Although 6
and 3 undergo one-electron reduction, respectively, generat-
ing an electrochemically unstable anion-radical from 6 and an
electrochemically stable anion-radical from 3, the one-
electron reduction potential [(Epc) V by CV] of 6 coincides
with that of 3 [21.76 (Epc) V by CV, see Fig. 5(a)].
and 21.72 V, while the corresponding two reversible redox
potentials determined by CV were located at the values of
þ0.49 (E1/2) and 21.75 (E1/2) V as shown in Figure 6(a) and
(b). From a comparative study of the redox potentials of 7
with those of 3 [see Fig. 5(a) and (b)], a plausible electron
transfer mechanism of 7 based on its CV and DPV data can
be inferred as shown in Scheme 5; namely, (i) 7 undergoes
two-electron oxidation at a potential of þ0.49 (E1/2) V by
CV (corresponding to þ0.51 V by DPV), generating an
electrochemically stable dication 7b via the cation-radical
7a and its resonance form 7a0. Thus, 7 is susceptible to two-
electron oxidation than 3; and (ii) 7 is reduced to the anion-
radical 7c at the potential of 21.75 (E1/2) V by CV
(corresponding to 21.72 V by DPV). Thus, the one-electron
reduction potential of 7 coincides with that of 3. As the
result, the CV and DPV data indicated 7 serves as an
electron donor. Along with the dication 7b generated from
7, the anion-radical 7c is also electrochemically stable.
1.12. Reaction of 2-(3-guaiazulenyl)-1,1-bis(4-methoxy-
phenyl)ethylene (3) with N-chlorosuccinimide (NCS)
The chemistry on stilbenes has been studied to a
considerable extent, and the physical and chemical proper-
ties, the biological activities, and the functions for those
numerous molecules have been well documented. For
example, it is well known that diethylstilbestrol (DES)17,18
and chlorotrianisene (13)17 exhibit significant estrogenic
activity. On the other hand, naturally occurring guaiazulene
(1a) has been widely used clinically as anti-inflammatory
and anti-ulcer agents. Furthermore, 3-chloroguaiazulene
(14) was isolated from a deep sea coral, gorgonian.19
Along with the title investigations, ‘reactions of
azulenes with 1,2-diaryl-1,2-ethanediols in methanol in
the presence of hydrochloric acid’, our interest has been
focused on preparation and estrogenic activity of 1-chloro-
1-(3-guaiazulenyl)-2,2-bis(4-methoxyphenyl)ethylene (15),
possessing a similar-type structure as 13, with a view to a
comparative study with the estrogenic activity of 13.
1.11. A comparative study of the electrochemical
behavior of (Z)-2-[4-(dimethylamino)phenyl]-1-(3-
guaiazulenyl)-1-phenylethylene (7) with that of 2-(3-
guaiazulenyl)-1,1-bis-(4-methoxyphenyl)ethylene (3)
The electrochemical behavior of 7 was measured under the
same electrochemical conditions as 3. Two redox potentials
observed by DPV were positioned at the Ep values of þ0.51

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5993
Figure 7. The reaction of 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3) with N-chlorosuccinimide (NCS) in hexane containing chloroform at
25 8C (and 60 8C) for 24 h under argon.
Similarly, as in the case of the preparation of 1-chloro-
azulene (1c) (see Section 3.1.5), the reactions of 2-(3-
guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3) with
N-chlorosuccinimide (NCS) at 25 8C (and 60 8C) were
carried out, giving the same result, as shown in Figure 7 and
Section 3.1.19. As the result, although this reaction did not
give the target compound 15, 1,1-bis(4-methoxyphenyl)-2-
{3-[5-(succinimidyl)guaiazulenyl]}ethylene (16) was
obtained in 10% yield, besides the recovered starting
material 3 (81%). The molecular structure of the product
16 was established on the basis of elemental analysis and
with that of 13 (and DES) are noteworthy, and are currently
under intensive investigation.
2. Conclusion
We have reported the following five points in this paper: (i)
although reaction of guaiazulene (1a) with 1,2-diphenyl-
1,2-ethanediol (2a) in methanol in the presence of
hydrochloric acid at 60 8C for 3 h under aerobic conditions
gave no product, reaction of 1a with 1,2-bis(4-methoxy-
phenyl)-1,2-ethanediol (2b) under the same reaction
conditions as 2a afforded a new ethylene derivative, 2-(3-
guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3), in
97% yield; (ii) similarly, reaction of methyl azulene-1-
carboxylate (1b) with 2b under the same reaction conditions
as 1a gave no product; however, reactions of 1-chloro-
azulene (1c) and the parent azulene (1d) with 2b under the
same reaction conditions as 1a afforded 2-[3-(1-chloro-
azulenyl)]-1,1-bis(4-methoxyphenyl)ethylene (4) (81%
yield), 2-azulenyl-1,1-bis(4-methoxyphenyl)ethylene (5)
(15% yield) and a chromatographically inseparable mixture
of several bis[bis(4-methoxyphenyl)vinyl]azulenes (50)
(41% yield), respectively; (iii) along with the above
reactions, reactions of 1a with 1,2-bis(4-hydroxyphenyl)-
1,2-ethanediol (2c) and 1-[4-(dimethylamino)phenyl]-2-
phenyl-1,2-ethanediol (2d) under the same reaction
conditions as 2b gave 2-(3-guaiazulenyl)-1,1-bis(4-hydro-
xyphenyl)ethylene (6) (73% yield) and (Z)-2-[4-(dimethyl-
amino)phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7)
(17% yield), respectively; (iv) comparative studies on the
above reaction products and their yields, crystal structures,
spectroscopic and electrochemical properties have been
reported and, further, a plausible reaction pathway for the
formation of the products 3–7 has been described; and (v)
reactions of 3 with N-chlorosuccinimide (NCS) in a mixed
solvent of hexane and chloroform (4:1, vol/vol) at 25 8C
(and 60 8C) for 24 h under argon respectively gave 1,1-
bis(4-methoxyphenyl)-2-{3-[5-(succinimidyl)guaiazul-
1
spectroscopic data [UV–vis, IR, EI-MS, H and 13C NMR
including 2D NMR (i.e. H–H COSY, NOESY, HMQC and
HMBC)] (see Section 3.1.19). Similarly, as in the case of
2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3),
1
the H NMR signals of 16 was carefully assigned using
the computer-assisted simulation analysis. In 1991 Nozoe
and his co-workers reported that the reaction of guaiazulene
(1a) with N-bromosuccinimide (NBS) in benzene at room
temperature for 30 min gave 1-(5-guaiazulenyl)succini-
mide, possessing a similar partial structure as 16, in 1%
yield along with eight other products, the recovered starting
material 1a (15%) and a polar resinous substance (18%
yield).20 Moreover, the electrochemical behavior of 16 was
measured under the same electrochemical conditions as 3
[see Fig. 5(a) and (b)]. As the result, it was found that 16
stepwise undergoes two-electron oxidation at the potentials
of þ0.64 (E1/2) and þ0.78 (E1/2) V by CV (corresponding to
þ0.66 and þ0.80 V by DPV), generating an electro-
chemically stable dication via an electrochemically
stable cation-radical and, further, 16 is reduced to the
anion-radical at the potential of 21.59 (E1/2) V by CV
(corresponding to 21.56 V by DPV), generating an
electrochemically stable anion-radical. Thus, although 16
is less susceptible to oxidation than 3, 16 is more susceptible
to reduction than 3, owing to the influence of the
succinimidyl group substituted at the C-5 position of the
3-guaiazulenyl group. Studies on the preparation of 15 and,
further, the estrogenic activity of 3–7, 9 and 16 compared

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M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
enyl]}ethylene (16) in 10% yield, besides the recovered
starting material 3 (81%).
ddd, J¼8.5, 2.5, 1.0 Hz, H-30,50,300,500) and 7.05 (4H, brd
ddd, J¼8.5, 2.05, 010 .0 Hz, H-20,60,200,600); 13C NMR (CD3CN),
d 159.9 (C-4 ,4 ), 134.4 (C-10,100), 129.4 (C-20,600,200,600),
114.0 (C-30,50,300,500), 79.0 (C-1,2) and 55.8 (MeO-4 ,400).
3. Experimental
3.1. General
3.1.2. Reaction of guaiazulene (1a) with 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b) in methanol in the
presence of hydrochloric acid. To a solution of com-
mercially available guaiazulene (1a) (50 mg, 252 mmol) in
methanol (1.0 mL) was added a solution of 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b) (60 mg, 219 mmol) in
methanol (1.5 mL) containing 36% hydrochloric acid
(0.2 mL) at 60 8C. The mixture was stirred at 60 8C for
3 h under aerobic conditions and then evaporated in vacuo.
The residue thus obtained was carefully separated by silica-
gel column chromatography (several times) with hexane–
ethyl acetate–benzene (90:5:5, vol/vol/vol) as an eluant.
The crude product, 2-(3-guaiazulenyl)-1,1-bis(4-methoxy-
phenyl)ethylene (3), thus obtained was recrystallized from
methanol to provide pure 3 as stable crystals (93 mg,
213 mmol, 97% yield).
Thermal (TGA/DTA) and elemental analyses were taken on
a Shimadzu DTG-50H thermal analyzer and a Yanaco MT-3
CHN corder, respectively. MALDI-TOF- and EI- (and
FAB-) MS spectra were taken on a Shimadzu/Kratos
Kompact-MALDI 4 and a JEOL The Tandem Mstation
JMS-700 TKM data system, respectively. UV–visible and
IR spectra were taken on a Beckman DU640 spectro-
photometer and
spectrometer, respectively. NMR spectra were recorded
a Shimadzu FTIR-4200 Grating
1
with a JEOL GX-500 (500 MHz for H and 125 MHz for
13C) cryospectrometer at 25 8C. The 1H NMR spectra were
assigned using the computer-assisted simulation analysis
(the software: gNMR developed by Adept Scientific plc) on
a DELL Dimension XPS T500 personal-computer with a
Pentium III processor. Cyclic and differential pulse
voltammograms were measured by an ALS Model 600
electrochemical analyzer.
Compound 3. Dark-green needles, mp 150 8C [determined
by thermal analysis (TGA and DTA)]. Found: C, 85.29; H,
7.44%. Calcd for C31H32O2: C, 85.28; H, 7.39%; Rf¼0.35
on silica-gel TLC (hexane–AcOEt–benzene¼90:5:5, vol/
vol/vol); UV–vis lmax (CH3CN) nm (log 1), 270 (4.33), 328
(4.24), 352sh (4.14), 408 (4.10) and 635 (2.54); IR nmax
(KBr) cm21, 2905, 2866 (C–H), 1605, 1508 (aromatic
CvC) and 1242, 1034 (C–O); MALDI-TOF-MS (without
any matrix reagent), m/z 436 (Mþ, 100%); exact EI-MS
(70 eV), found: m/z 436.2398 (Mþ, 100%); calcd for
3.1.1. Preparation of 1,2-bis(4-methoxyphenyl)-1,2-
ethanediol (2b). To a powder of NaBH4 (100 mg,
2.64 mmol) was added
a solution of commercially
available 1,2-bis(4-methoxyphenyl)-1,2-ethanedione (500
mg, 1.85 mmol) in ethanol (5 mL). The mixture was stirred
at 25 8C for 30 min. The crude product, 1,2-bis(4-methoxy-
phenyl)-1,2-ethanediol (2b), thus obtained was recrystal-
lized from ethanol–water (1:3, vol/vol) to provide a ca. 3:1,
chromatographically inseparable mixture of meso (1R,2S)-
1,2-bis(4-methoxyphenyl)-1,2-ethanediol (2b0) and two
enantiomeric, (1R,2R)- and (1S,2S)-1,2-bis(4-methoxy-
phenyl)-1,2-ethanediol (2b00), forms as stable crystals
(380 mg, 1.39 mmol, 75% yield).
1
C31H32O2: Mþ, m/z 436.2402. H NMR (C6D6), signals
based on the 3-guaiazulenyl group at d 1.16 (6H, d,
J¼6.9 Hz, (CH3)2CH-7000), 2.31 (3H, brd s, Me-1000), 2.70
(1H, sept, J¼6.9 Hz, Me2CH-7000), 2.94 (3H, s, Me-4000),
6.63 (1H, d, J¼10.6 Hz, H-5000), 7.02 (1H, dd, J¼10.6,
2.0 Hz, H-6000),0007.44 (1H, brd s, H-2000), 7.91 (1H, d,
J¼2.0 Hz, H-8 ) and signals based on the 1,1-bis(4-
methoxyphenyl) groups at d 3.24 (3H, s, MeO-40), 3.33
(3H, s, MeO-400), 6.70 (2H, ddd, J¼8.5,020 .5, 1.0 Hz, H-30,50),
6.84 (2H, ddd, J¼8.5, 2.50, 1.0 Hz, H-3 ,500), 7.38 (2H, ddd,
J¼8.5, 2.5,00 1.0 Hz, H-2 ,60), 7.49(2H, ddd, J¼8.5, 2.5,
1.0 Hz, H-2 ,600) and a signal based on the .CvCH– unit
Compound 2b. White plates, mp 167 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 70.26; H,
6.52%. Calcd for C16H18O4: C, 70.06; H, 6.61%; exact
EI-MS (70 eV), found: m/z 274.1187 (Mþ, 54%) and
256.1085 ([M2H2O]þ, 100%); calcd for C16H18O4: Mþ,
m/z 274.1205 and [M2H2O]þ, m/z 256.1099; IR nmax (KBr)
cm21, 3344 (O–H), 2901, 2835 (C–H), 1612, 1516
(aromatic CvC) and 1254, 1030 (C–O). The0 relative
00
13
at d 7.77 (1H, brd s, H-2); C NMR (C6D6), d 159.6 (C-4 ),
000
000
159.1 (C-40), 146.2 (C-4 ), 140.4 (C-2000), 140.2 (C-7 ),
000
139.7 (C-80a00000), 138.7 (C-1), 137.7 (C-100), 135.5 (C-3a ),
134.6 (C-600 ),00134.0 (C-10),0010 33.2 (C-20,60), 133.2 (C-8000),
129.6 (C-2 ,6 ), 127.2 (C-3 ), 126.5 (C-5000), 125.6 (C-2),
125.1 (C-1000), 114.1 (C-30,50), 114.100(0C-300,500), 54.8 (MeO-
400), 54.6 (MeO-40), 37.9 (Me2CH-7 ), 27.8 (Me-4000), 24.5
((CH3)2CH-7000) and 12.9 (Me-1000).
1
intensity of the H NMR signals for the meso 2b and the
enantiomers 2b00 showed a ratio of ca. 3:1.
0
1
Compound 2b . H NMR (CD3CN), d 3.21, 3.22 (1H each,
dd, J¼4.6, 2.6 Hz, OH-1,2), 3.77 (6H, s, MeO-40,400), 4.645,
4.653 (1H each, brd dd, J¼4.6, 2.60Hz, H-1,2), 6.83 (4H,
brd ddd, J¼8.5, 2.5, 1.0 Hz, H-30,50,3000,500) and 7.15 (4H,
3.1.3. X-ray crystal structure of 2-(3-guaiazulenyl)-1,1-
bis(4-methoxyphenyl)ethylene (3). A total 6319 reflections
with 2umax¼55.08 were collected on a Rigaku AFC-5R
automated four-circle diffractometer with graphite mono-
brd ddd, J¼8.5, 2.5, 1.00Hz, H-2 ,6 ,200,600); C NMR
13
(CD3CN), d 159.9 (C-4 ,400), 134.9 (C-10,100), 129.4
(C-20,60,200,600), 113.9 (C-30,50,300,500), 78.0 (C-1,2) and 55.8
(MeO-40, 400).
˚
chromated Mo-Ka radiation (l¼0.71069 A, rotating anode:
50 kV, 180 mA) at 296 K. The structure was solved by
direct methods (SIR97) and expanded using Fourier
techniques (DIRDIF94). The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included but
not refined. The final cycle of full-matrix least-squares
Compound 2b00. 1H NMR (CD3CN), d 3.68, 3.69 (1H each,
dd, J¼6.0, 2.3 Hz, OH-1,2), 3.73 (6H, s, MeO-40,400), 4.55,
4.54 (1H each, brd dd, J¼6.0, 2.3 Hz, H-1,2), 6.76 (4H, brd

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5995
refinement was based on F 2. All calculations were
performed using the teXsan crystallographic software
package. Crystallographic data have been deposited at the
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK and
copies can be obtained on request, free of charge, by quoting
the publication citation and the deposition number CCDC
200992.
recrystallized from methanol to provide pure 4 as stable
crystals (54 mg, 135 mmol, 81% yield).
Compound 4. Dark-green prisms, mp 137 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 77.88; H,
5.42%. Calcd for C26H21ClO2: C, 77.90; H, 5.28%; Rf¼0.14
on silica-gel TLC (hexane–AcOEt–benzene¼90:5:5, vol/
vol/vol); UV–vis lmax (CH3CN) nm (log 1), 268 (4.48), 328
(4.44), 358 (4.24), 407 (4.22) 657 (2.58) and 665 (2.58); IR
Crystallographic data for 3: C31H32O2 (FW¼436.59), dark-
green needle [from ethyl acetate–methanol¼1:5 (vol/vol),
the crystal size, 0.40£0.20£0.50 mm3], monoclinic, P21/n
n
max (KBr) cm21, 2927, 2831 (C–H), 1609, 1508 (aromatic
CvC), 1242, 1034 (C–O) and 740 (C–Cl); exact EI-MS
(70 eV), found: m/z 400.1219 (Mþ, 100%); calcd for
˚
˚
˚
(#14), a¼15.427(2) A, b¼10.103(3) A, c¼16.706(2) A,
3
1
b¼105.371(9)8, V¼2510.5(8) A , Z¼4, Dcalcd¼1.155 g/
C26H21ClO2: Mþ, m/z 400.1230. H NMR (C6D6), signals
˚
cm3, m(Mo-Ka)¼0.70 cm21, scan width¼(1.52þ0.30
tan u)8, scan mode¼v22u, scan rate¼8.08/min, measured
reflections¼6319, observed reflections¼3574, no. of
parameters¼298, R1¼0.052, wR2¼0.160 and goodness of
fit indicator¼1.22.
based on the 3-(1-chloroazulenyl) group at d 6.53 (1H, dd,
J¼9.6, 9.6 Hz, H-7000), 6.56 (1H,000dd, J¼9.6, 9.6 Hz, H-5000),
7.00 (1H, dd, J¼9.6, 9.6 Hz, H-6 ), 7.40 (1H, s, H-2000), 8.06
(1H, d, J¼9.6 Hz, H-8000), 8.07 (1H, d, J¼9.6 Hz, H-4000) and
signals based on the 1,1-bis(4-methoxyphenyl) groups at d
3.26 (3H, s, MeO-40), 3.303 (3H, s, MeO-400), 6.75 (2H, ddd,
J¼8.5, 2.3,00 1.4 Hz, H-3 ,50), 6.84 (2H, ddd, J¼8.7, 02.05,
1.5 Hz, H-3 ,500), 7.23 (2H, ddd, J¼8.5, 2.030 , 1.4 Hz, H-2 ,6 ),
7.43 (2H, ddd, J¼8.7, 2.5, 1.5 Hz, H-2 ,600) and a signal
based on the .CvCH– unit at d 7.38 (1H, s, H-2); 13C
NMR (C6D6), d 159.9 (C-400), 159.8 (C-40), 140.0 (C-1),
3.1.4. Reaction of methyl azulene-1-carboxylate (1b)
with 1,2-bis(4-methoxyphenyl)-1,2-ethanediol (2b) in
methanol in the presence of hydrochloric acid. To a
solution of methyl azulene-1-carboxylate21 (1b) (41 mg,
220 mmol), whose compound was prepared according to a
method based on the references,22,23 in methanol (1.0 mL)
was added a solution of 1,2-bis(4-methoxyphenyl)-1,2-
ethanediol (2b) (60 mg, 219 mmol) in methanol (1.5 mL)
containing 36% hydrochloric acid (0.2 mL) at 60 8C. The
mixture was stirred at 60 8C for 3 h under aerobic conditions
and then evaporated in vacuo. No product was observed by
silica-gel TLC [solv. hexane–ethyl acetate (8:2, vol/vol)] of
the residue thus obtained. Furthermore, the thus-obtained
residue was carefully separated by silica-gel column
chromatography with hexane–ethyl acetate (8:2, vol/vol)
as an eluant, giving only the starting material 1b (40 mg).
No product was obtained.
000
139.3 (C-6 ), 137.1 (C-100), 136.8 (C-3a000), 135.4 (C-8a000),
000
000
134.8 (C-2 ), 134.6 (C-8000), 134.5 (C-4 ), 133.7 (C-10),
132.0 (C-20,0060 0), 129.2 (C-200,600), 126.0 (C-3 ), 123.5 (C-7000),
000
122.8 (C-5 ), 118.1 (C-1000), 117.8 (C-2), 114.8 0(C-30,50),
114.1 (C-300,500), 54.9 (MeO-400) and 54.7 (MeO-4 ).
3.1.7. X-ray crystal structure of 2-[3-(1-chloroazulenyl)]-
1,1-bis(4-methoxyphenyl)ethylene (4).
A total 5477
reflections with 2umax¼55.08 were collected on a Rigaku
AFC-5R automated four-circle diffractometer with graphite
˚
monochromated Mo-Ka radiation (l¼0.71069 A, rotating
anode: 50 kV, 180 mA) at 296 K. The structure was solved
by direct methods (SIR97) and expanded using Fourier
techniques (DIRDIF94). The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included but
not refined. The final cycle of full-matrix least-squares
refinement was based on F 2. All calculations were
performed using the teXsan crystallographic software
package. CCDC No.: 225123.
3.1.5. Preparation of 1-chloroazulene (1c). Compound 1c
was prepared according to a method based on the
reference.23 To a solution of N-chlorosuccinimide (NCS)
(150 mg, 1.12 mmol) in hexane (15 mL) was added a
solution of commercially available azulene (1d) (100 mg,
0.78 mmol) in hexane (5.0 mL). The mixture was stirred at
25 8C for 18 h under argon and then evaporated in vacuo.
The residue thus obtained was carefully separated by silica-
gel column chromatography with hexane as an eluant,
giving pure 1-chloroazulene23 (1c) as a blue paste (89 mg,
0.55 mmol, 71% yield).
Crystallographic data for 4: C26H21ClO2 (FW¼400.90),
dark-green prism [from methanol, the crystal size,
0.40£0.30£0.50 mm3], monoclinic, P21/n (#14), a¼
˚
˚
˚
6.280(2) A, b¼13.481(4) A, c¼24.902(1) A, b¼94.78(1)8,
V¼2101.0(7) A , Z¼4, Dcalcd¼1.267 g/cm3, m(Mo-
3
˚
3.1.6. Reaction of 1-chloroazulene (1c) with 1,2-bis(4-
methoxyphenyl)-1,2-ethanediol (2b) in methanol in the
presence of hydrochloric acid. To a solution of 1-chloro-
azulene (1c) (27 mg, 166 mmol) in methanol (1.0 mL) was
added a solution of 1,2-bis(4-methoxyphenyl)-1,2-ethane-
diol (2b) (75 mg, 275 mmol) in methanol (1.5 mL) contain-
ing 36% hydrochloric acid (0.18 mL) at 60 8C. The mixture
was stirred at 60 8C for 3 h under aerobic conditions and
then evaporated in vacuo. The residue thus obtained was
carefully separated by silica-gel column chromatography
with hexane–ethyl acetate–benzene (90:5:5, vol/vol/vol) as
an eluant. The starting material 1c (2 mg, 12 mmol, 7%) was
recovered. The crude product, 2-[3-(1-chloroazulenyl)]-1,1-
bis(4-methoxyphenyl)ethylene (4), thus obtained was
Ka)¼2.01 cm21, scan width¼(0.73þ0.30 tan u)8, scan
mode¼v, scan rate¼8.08/min, measured reflections¼5477,
observed reflections¼2704, no. of parameters¼262,
R1¼0.039, wR2¼0.116 and goodness of fit indicator¼1.25.
3.1.8. Reaction of azulene (1d) with 1,2-bis(4-methoxy-
phenyl)-1,2-ethanediol (2b) in methanol in the presence
of hydrochloric acid. To a solution of commercially
available azulene (1d) (35 mg, 273 mmol) in methanol
(1.0 mL) was added a solution of 1,2-bis(4-methoxyphe-
nyl)-1,2-ethanediol (2b) (30 mg, 109 mmol) in methanol
(1.5 mL) containing 36% hydrochloric acid (0.2 mL) at
60 8C. The mixture was stirred at 60 8C for 3 h under aerobic
conditions and then evaporated in vacuo. The residue thus

5996
M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
obtained was carefully separated by silica-gel column
chromatography (several times) with hexane–ethyl
acetate–benzene (90:5:5, vol/vol/vol) as an eluant, giving
the recovered starting material 1d (8 mg, 62.4 mmol, 23%),
2-azulenyl-1,1-bis(4-methoxyphenyl)ethylene (5) as a dark-
green paste (6 mg, 16.4 mmol, 15% yield) and a chromato-
graphically inseparable mixture of bis[bis(4-methoxy-
phenyl)vinyl]azulenes (50). The product 5 thus obtained
was recrystallized from hexane–ethyl acetate–benzene
(90:5:5, vol/vol/vol) to provide pure 5 as stable crystals. A
mixture of 50 thus obtained was recrystallized from ethyl
acetate–methanol (1:5, vol/vol) to provide 50 as stable
crystals (27 mg, 45 mmol, 41% yield).
Compound 2a. White plates, mp 132 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 78.82; H,
6.58%. Calcd for C14H14O2: C, 78.48; H, 6.59%; exact
EI-MS (70 eV), found: m/z 214.1004 (Mþ, 46%) and
196.0918 ([M2H2O]þ, 100%); calcd for C14H14O2: Mþ,
m/z 214.0994 and [M2H2O]þ, m/z 196.0888; IRnmax (KBr)
cm21, 3371, 3310 (O–H), 2901 (C–H), 1601, 1497
(aromatic CvC) and 1281, 1034 (C–O). The0 relative
1
intensity of the H NMR signals for the meso 2a and the
enantiomers 2a00 showed a ratio of ca. 25:1.
0
1
Compound 2a . H NMR (CD3CN), d 3.36, 3.37 (1H each,
dd, J¼4.6, 2.9 Hz, OH-1,2), 4.75, 4.76 (1H each, brd dd,
J¼4.6, 2.9 Hz, H-1,2) and 7.20–7.30 (10H, m, protons for
two phenyl groups); 13C NMR (CD3CN), d 142.7 (C-10,100),
128.06 (C-20,60,200,600), 128.24 (C-30,50,300,500), 128.15
(C-4 ,400) and 78.4 (C-1,2).
Compound 5. Dark-green blocks, mp 145 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 85.19; H,
6.15%. Calcd for C26H22O2: C, 85.22; H, 6.05%; Rf¼0.25
on silica-gel TLC (hexane–AcOEt–benzene¼90:5:5, vol/
vol/vol); UV–vis lmax (CH3CN) nm (log 1), 225sh (4.38),
265 (4.49), 308sh (4.37), 320 (4.43), 347 (4.33), 403 (4.25)
and 639 (2.46); IR nmax (KBr) cm–1, 3017, 2835 (C–H) and
1605, 1508 (aromatic CvC) and 1246, 1030 (C–O); exact
EI-MS (70 eV), found: m/z 366.1621 (Mþ, 100%); calcd for
00
1
Compound 2a . H NMR (CD3CN), d 3.75, 3.76 (1H, dd,
J¼6.0, 2.3 Hz, OH-1,2), 4.64, 4.65 (1H each, brd dd, J¼6.0,
2.3 Hz, H-1,2) and 7.20–7.30 (10H, m, protons for two
phenyl groups).
1
C26H22O2: Mþ, m/z 366.1620. H NMR (C6D6), signals
3.1.10. Reaction of guaiazulene (1a) with 1,2-diphenyl-
1,2-ethanediol (2a) in methanol in the presence of
hydrochloric acid. To a solution of commercially available
guaiazulene (1a) (50 mg, 252 mmol) in methanol (1.0 mL)
was added a solution of 1,2-diphenyl-1,2-ethanediol (2a)
(60 mg, 219 mmol) in methanol (1.5 mL) containing 36%
hydrochloric acid (0.2 mL) at 60 8C. The mixture was
stirred at 60 8C for 3 h under aerobic conditions and then
evaporated in vacuo. No product was observed by silica-
gel TLC [solv. hexane–ethyl acetate–benzene (90:5:5, vol/
vol/vol)] of the residue thus obtained. Furthermore, the
thus-obtained residue was carefully separated by silica-
gel column chromatography with hexane–ethyl
acetate–benzene (90:5:5, vol/vol/vol) as an eluant, giving
only the starting material 1a (49 mg). No product was
obtained.
based on the azulenyl group at d 6.63 (1H, dd, J¼9.8,
9.8 Hz, H-5000), 6.72 (1H, dd, J¼9.8, 9.8 Hz, H-7000), 7.07
(1H, d, J¼4.0 Hz, H-3000), 7.11 (1H, dd, J¼9.8, 9.8 Hz,
H-6000), 7.58 (1H, d, J¼4.0 Hz, H-2000), 7.72 (1H, d,
J¼9.8 Hz, H-4000), 8.26 (1H, d, J¼9.8 Hz, H-8000) and signals
based on the 1,1-bis(4-methoxyphenyl) groups at d 7.49
(2H, ddd, J¼8.6, 2.5, 1.00 Hz, H-200,600), 7.33 (2H, ddd,
J¼8.6, 2.5,00 1.0 Hz, H-20,6 ), 6.87 (2H, ddd, J¼8.6, 02.05,
1.0 Hz, H-3 ,500), 6.82 (2H, ddd, J¼8.6, 2.5, 1.0 Hz, H-3 ,5 ),
3.34 (3H, s, MeO-400), 3.31 (3H, s, MeO-40) and a signal
13
based on the .CvCH– unit at d 7.58 (1H, s, H-2);
C
000
NMR (C6D6), d 159.7 (C-400), 159.6 (C-40), 142.4 (C-3a ),
000
139.8 (C-1), 137.7 (C-6000), 137.61 (C-8a000), 137.58 (C-2 ),
000
137.5 (C-100)0, 136.3 (C-4000), 134.5 (C-10), 133.9 (C-8 ),
132.3 (C-200,060 ), 129.2 (C-200,600), 128.1 (C-1000), 123.7 (C-5000),
122.3 (C-7 ), 119.3 (C-2), 1010 9.0 (C-3000), 114.6 0(C-30,50),
113.7 (C-300,500), 54.8 (MeO-4 ) and 54.7 (MeO-4 ).
3.1.11. Preparation of 1,2-bis(4-hydroxyphenyl)-1,2-
powder of NaBH4 (50 mg,
a solution of commercially
ethanediol (2c). To
1.32 mmol) was added
a
Compound 50. Dark-green prisms, mp .220 8C [decomp.,
determined by thermal analysis (TGA and DTA)]. Found:
C, 82.82; H, 6.12%. Calcd for C42H36O4: C, 83.42; H,
6.00%; Rf¼0.03 on silica-gel TLC (hexane–AcOEt–
benzene¼90:5:5, vol/vol/vol); IR nmax (KBr) cm21, 2997,
2831 (C–H) and 1605, 1508 (aromatic CvC) and 1246,
1034 (C–O); exact EI-MS (70 eV), found: m/z 604.2614
(Mþ, 100%); calcd for C42H36O4: Mþ, m/z 604.2613.
available 1,2-bis(4-hydroxyphenyl)-1,2-ethanedione (100
mg, 0.41 mmol) in methanol (3.0 mL). The mixture was
stirred at 0 8C for 1 h. After the reaction, distilled-water
(10 mL) was added to the mixture and then the resulting
product was extracted with diethyl ether (10 mL£3). The
extract was evaporated in vacuo. The crude product, 1,2-
bis(4-hydroxyphenyl)-1,2-ethanediol (2c), thus obtained
was recrystallized from ethanol to provide a ca. 12:1,
chromatographically inseparable mixture of meso (1R,2S)-
1,2-bis(4-hydroxyphenyl)-1,2-ethanediol (2c0), and two
enantiomeric, (1R,2R)- and (1S,2S)-1,2-bis(4-hydroxy-
phenyl)-1,2-ethanediol (2c00), forms as stable crystals
(51 mg, 0.21 mmol, 51% yield).
3.1.9. Preparation of 1,2-diphenyl-1,2-ethanediol (2a).
To a powder of NaBH4 (100 mg, 2.64 mmol) was added a
solution of commercially available 1,2-diphenyl-1,2-
ethanedione (500 mg, 2.38 mmol) in ethanol (5 mL). The
mixture was stirred at 25 8C for 30 min. The crude product,
1,2-diphenyl-1,2-ethanediol (2a), thus obtained was
recrystallized from ethanol–water (1:3, vol/vol) to provide
a ca. 25:1, chromatographically inseparable mixture of meso
(1R,2S)-1,2-diphenyl-1,2-ethanediol (2a0), and two enantio-
meric, (1R,2R)- and (1S,2S)-1,2-diphenyl-1,2-ethanediol
(2a00), forms as stable crystals (350 mg, 1.63 mmol, 68%
yield).
Compound 2c. White plates, mp .177 8C [decomp.
determined by thermal analysis (TGA and DTA)]. Found:
C, 68.81; H, 5.71%. Calcd for C14H14O4: C, 68.28; H,
5.73%; exact FAB-MS (3-nitrobenzyl alcohol matrix),
found: m/z 246.0906; calcd for C14H14O4: Mþ, m/z
1
246.0892. The relative intensity of the H NMR signals

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5997
for the meso 2c0 and the enantiomers 2c00 showed a ratio of
ca. 12:1.
115.3 (C-300,500), 37.9 (Me2CH-7000), 27.8 (Me-4000), 24.5
((CH3)2CH-7000), 12.8 (Me-1000).
0
1
Compound 2c . H NMR (CD3OD), d 4.63 (2H, s, H-1,2),
6.68 (4H, brd ddd, J¼8.6, 2.5, 1.0 Hz, H-30,50,300,500) and
7.04 (4H, brd ddd, J¼8.6, 2.50, 1.0 Hz, H-20,60,200,600); 13C
NMR (CD3OD), d 157.7 (C-4 ,400), 133.7 (C-10,100), 129.8
(C-20,60,200,600), 115.5 (C-30,50,300,500) and 78.8 (C-1,2).
3.1.13. Preparation of 1-[4-(dimethylamino)phenyl]-2-
phenyl-1,2-ethanediol (2d). To a powder NaBH4 (100 mg,
2.64 mmol) was added a solution of commercially available
4-(dimethylamino)benzoin (400 mg, 1.57 mmol) in ethanol
(5 mL). The mixture was stirred at 25 8C for 1 h. After the
reaction, distilled-water (15 mL) was added to the mixture
and then the resulting product was extracted with diethyl
ether (15 mL£2). The extract was dried (MgSO4) and
evaporated in vacuo. The pure product, 1-[4-(dimethyl-
amino)phenyl]-2-phenyl-1,2-ethanediol (2d), was obtained
as stable crystals (365 mg, 1.41 mmol, 90% yield).
00
1
Compound 2c . H NMR (CD3OD), d 4.50 (2H, s, H-1,2),
6.58 (4H, brd ddd, J¼8.6, 2.5, 1.0 Hz, H-30,50,300,500)
and 6.89 (4H, brd ddd, J¼8.6, 2.5, 1.0 Hz, H-20,60,2000,600);
13C NMR (CD3OD), d 157.7 (C-40,400), 133.5 (C-1 ,100),
129.6 (C-20,60,200,600), 115.5 (C-30,50,300,500) and 80.1
(C-1,2).
Compound 2d. White plates, mp 109 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 74.74; H,
7.42; N, 5.43%. Calcd for C16H19NO2: C, 74.68; H, 7.44; N,
5.44%; exact FAB-MS (3-nitrobenzyl alcohol matrix),
found: m/z 257.1426; calcd for C16H19NO2: Mþ, m/z
257.1416. H NMR (CD3CN), d 2.90 (6H, s, (CH3)2N-4 ),
3.12 (1H, d, J¼4.0 Hz, OH-2), 3.21 (1H, d, J¼4.0 Hz,
OH-1), 4.62 (1H, dd, J¼6.0, 4.0 Hz, H-2), 4.70 (1H, dd,
J¼6.0, 4.0 Hz, H-1), 6.67 (2H, brd ddd, J¼8.9, 2.5,0 1.0 Hz,
H-30,50), 7.09 (2H, brd ddd, J¼8.9, 2.5, 1.0 Hz, H-2 ,60) and
7.22–7.31 (5H, m, protons for a phenyl group); 13C NMR
(CD3CN), d 151.3 (C-40), 143.2 (C-100), 130.3 (C-10), 129.1
(C-20,60), 128.6 (C-200,600), 128.3 (C-300,500), 128.0 (C-400),
112.8 (C-30,50), 78.5 (C-1), 78.3 (C-2) and 40.8 ((CH3)2N-
40).
3.1.12. Reaction of guaiazulene (1a) with 1,2-bis(4-
hydroxyphenyl)-1,2-ethanediol (2c) in methanol in the
presence of hydrochloric acid. To a solution of com-
mercially available guaiazulene (1a) (18 mg, 91 mmol) in
methanol (1.0 mL) was added a solution of 1,2-bis(4-
hydroxyphenyl)-1,2-ethanediol (2c) (20 mg, 81 mmol) in
methanol (1.5 mL) containing 36% hydrochloric acid
(0.2 mL) at 60 8C. The mixture was stirred at 60 8C for
3 h under aerobic conditions. After the reaction, distilled-
water (10 mL) was added to the mixture and then the
mixture was extracted with diethyl ether (10 mL£2). The
extract was washed with water, dried (MgSO4) and
evaporated in vacuo. The residue thus obtained was
carefully separated by silica-gel column chromatography
with hexane–ethyl acetate–benzene (7:2:1, vol/vol/vol) as
an eluant. The starting material 1a (5 mg, 25 mmol, 27%)
was recovered. The crude product, 2-(3-guaiazulenyl)-1,1-
bis(4-hydroxyphenyl)ethylene (6), thus obtained was
recrystallized from benzene to provide pure 6 as stable
crystals (24 mg, 59 mmol, 73% yield).
0
1
3.1.14. Reaction of guaiazulene (1a) with 1-[4-(dimethyl-
amino)phenyl]-2-phenyl-1,2-ethanediol (2d) in methanol
in the presence of hydrochloric acid. To a solution of
commercially available guaiazulene (1a) (46 mg,
232 mmol) in methanol (1.0 mL) was added a solution of
1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-ethanediol (2d)
(60 mg, 233 mmol) in methanol (2.0 mL) containing 36%
hydrochloric acid (0.2 mL) at 60 8C. The mixture was
stirred at 60 8C for 3 h under aerobic conditions. After the
reaction, the reaction solution was carefully neutralized
with aq. NaHCO3 and then the mixture was extracted with
diethyl ether (10 mL£2). The extract was washed with
water, dried (MgSO4) and evaporated in vacuo. The residue
thus obtained was carefully separated by silica-gel column
chromatography (several times) with hexane–benzene (6:4,
vol/vol) as an eluant. The starting material 1a (3 mg,
15 mmol, 7%) was recovered. The crude product, (Z)-2-[4-
(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1-phenylethyl-
ene (7), thus obtained was recrystallized from methanol–
AcOEt (5:1, vol/vol) to provide pure 7 as stable crystals
(17 mg, 40.5 mmol, 17% yield).
Compound 6. Dark-green prisms, mp 123 8C [determined by
thermal analysis (TGA and DTA)]. Found: C, 85.44; H,
6.73%. Calcd for C29H28O2: C, 85.26; H, 6.91%; Rf¼0.15
on silica-gel TLC (hexane–AcOEt–benzene¼7:2:1, vol/
vol/vol); UV–vis lmax (CH3CN) nm (log 1), 270 (4.42), 327
(4.34), 348 (4.25), 406 (4.18) and 636 (2.74); IR nmax (KBr)
cm21, 3395 (O–H), 2959, 2866 (C–H) and 1609, 1509
(aromatic CvC); exact EI-MS (70 eV), found: m/z
408.2078 (Mþ, 100%); calcd for C29H28O2: Mþ, m/z
408.2089. 1H NMR (C6D6), signals based on the 3-
guaiazulenyl group at d 1.16 (60H00 , d, J¼6.9 Hz,
(CH3)2CH-7000), 2.29 (3H, brd s, Me-1 ), 2.69 (1H, sept,
J¼6.9 Hz, Me2CH-7000), 2.89 (3H, s, Me-4000), 6.60 (1H, d,
J¼10.6 Hz, H-5000), 7.00 (1H, dd, J¼10.6, 2.0 Hz, H-6000),
7.37 (1H, brd s, H-2000), 7.89 (1H, d, J¼2.0 Hz, H-8000) and
signals based on the 1,1-bis(4-hydroxyphenyl) groups at d
3.95 (1H, s, OH-40), 4.05 (1H, s, OH-400), 6.41 (2H, ddd,
J¼8.6, 2.5, 1.0 Hz, H-30,50), 6.53 (2H, ddd, J¼8.5, 02.05,
1.0 Hz, H-300,500), 7.24 (2H, ddd, J¼8.5, 2.050 , 1.0 Hz, H-2 ,6 ),
Compound 7. Dark-green prisms, mp 166 8C [determined by
thermal amalysis (TGA and DTA)]. Found: C, 88.62; H,
7.93; N, 3.35%. Calcd for C31H33N: C, 88.74; H, 7.93; N,
3.34%; Rf¼0.15 on silica-gel TLC (hexane–benzene¼6:4,
vol/vol); UV–vis lmax (CH3CN) nm (log 1), 244 (4.30), 288
(4.45), 305sh (4.28), 349 (4.30), 372sh (4.13), 619 (2.61),
672sh (2.52) and 744sh (2.07); exact FAB-MS (3-nitroben-
zyl alchol matrix), found: m/z 419.2620; calcd for C31H33N:
7.34 (2H, ddd, J¼8.5, 2.5, 1.0 Hz, H-2 ,600) and a signal
13
based on the .CvCH– unit at d 7.69 (1H, s, H-2);
C
000
NMR (C6D6), d 155.7 (C-400), 155.3 (C-40), 146.2 (C-4 ),
140.3 (C-2 ), 140.2 (C-7 ), 139.7 (C-8a000), 138.6 (C-1),
000
000
000
137.5 (C-1 ), 135.4 (C-3a ), 134.5 (C-6000), 133.9 (C-10),
133.2 (C-20,0060 0), 133.1 (C-8000), 129.6 (C-200,600), 127.1 (C-3000),
126.5 (C-5 ), 125.4 (C-2), 125.1 (C-1000), 115.4 (C-30,50),
00
1
Mþ, m/z 419.2613. H NMR (C6D6), signals based on the
3-guaiazulenyl group at d 1.21 (6H, d, J¼6.9 Hz,

5998
M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
(CH3)2CH-70), 2.59 (3H, brd s, Me-10), 2.79 (1H, sept,
J¼6.9 Hz, (CH3)2CH-70), 2.84 (3H, brd s, Me-40), 6.67
(1H, brd d,0 J¼10.9 Hz, H-50), 7.10 (1H, brd dd, J¼10.9,
2.0 Hz, H-6 ), 7.60 (1H, brd s, H-20), 8.25 (1H, d, J¼2.0 Hz,
H-80) and signals based on the 4-(dimethylamino)phenyl
group at d 2.29 (6H, s, (CH3)2N-4000), 6.20 (2H, ddd, J¼9.0,
2.5,0010 .0 Hz, H-3000,5000), 7.039 (2H, ddd, J¼9.0, 2.5, 1.0 Hz,
H-2 ,6000) and signals based on the phenyl group at d 7.040
(1H, brd dddd, J¼7.7, 7.7, 1.5, 1.5 Hz, H-400), 070 .116, 7.119
(1H each, brd ddd, J¼7.7, 7.7, 1.5 Hz, H-3 ,500), 7.400,
7.413 (1H each, brd ddd, J¼7.7, 1.5, 1.5 Hz, H-200,600), and a
signal based on the –HCvCr unit at d 7.40 (1H, s, H-2);
13C NMR (C6D6), d 149.4 (C-4000), 146.9 (C-40), 145.8
(C-100), 141.0 (C-20), 139.4 (C-70), 138.6 (C-8a0), 136.8
(C-10)00, 135.0 (C-60), 134.4 (C-3a0),00 133.4 (C-80), 130.8
(C-2000,6000), 129.4 (C-2), 128.5 (C-300,5 ), 127.5 (C-30), 127.2
(C-10 ), 126.9 (C-200,600), 126.8 (C-50), 126.5 (C-400), 125.9
(C-1 ), 112.4 (C-3000,5000), 39.7 ((CH3)2N-4000), 38.1
((CH3)2CH-70), 25.6 (Me-40), 24.7 ((CH3)2CH-70) and 13.1
(Me-10).
determined by thermal analysis (TGA and DTA)]. Found:
C, 64.87; H, 5.99%. Calcd for C32H36B2F8: C, 64.68; H,
6.11%; UV–vis lmax (CF3COOH) nm (log 1), 255 (4.63),
318 (4.29), 407 (4.39), 432sh (4.41), 466 (4.51) and 526
(4.64); IR nmax (KBr) cm21, 1056 and 520 (BF24 ); exact
FAB-MS (3-nitrobenzyl alcohol matrix), found: m/z
420.2814; calcd for C32H36: [M22BF4]þ, m/z 420.2817.
1H NMR (CF3COOD), signals based on the a,a0-bis(3-
guaiazulenylmethylium) moiety with a delocalized
p-electron system at d 1.38 (12H, d, J¼7.0 Hz,
(CH3)2CH-7,70), 2.43 (6H, s, Me-1,10), 3.34 (6H, s, Me-
4,40), 3.35 (2H, sept, J¼7.0 Hz, Me2CH-7,70), 7.88 (2H, brd
s, H-2,20), 8.30 (2H0, dd, J¼11.0, 2.0 Hz, H-6,60), 8.47 (2H,
d, J¼2.0 Hz, H-8,8 ), 8.408 (2H, d, J¼11.0 Hz, H-5,50) and
8.73 (2H, brd s, HCþ-a,a ); 13C NMR (CF3COOD), d 177.6
(C-7,70), 164.5 (C-8a,8a0), 159.6 (C-4,40), 153.8 (C-3a,3a00),
153.2 (C-5,50), 150.7 (C-1,10), 150.6 (C-3,30), 146.2 (C-6,6 ),
139.6 (C-8,80), 138.4 (HCþ-a,a0), 138.0 (C-2,20), 41.7
(Me2CH-7,70), 28.9 (Me-4,40), 23.4 ((CH3)2CH-7,70) and
13.6 (Me-1,10).
3.1.15. X-ray crystal structure of (Z)-2-[4-(dimethyl-
amino)phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7).
A total 5981 reflections with 2umax¼55.08 were collected
on a Rigaku AFC-5R automated four-circle diffractometer
with graphite monochromated Mo-Ka radiation
3.1.17. Preparation of (E)-1,2-di(3-guaiazulenyl)ethylene
(9). To a solution of 8 (80 mg, 134.6 mmol) in trifluoroacetic
acid (2 mL) was added a zinc powder (440 mg, 6.73 mmol)
under argon. The mixture was stirred at 0 8C for 5 min under
argon. After the reaction, the zinc powder was removed by
using a centrifugal separator. The reaction solution was
carefully neutralized with aq. NaHCO3 and then the
resulting product was extracted with hexane (20 mL£2).
The extract was washed with water, dried (MgSO4) and
evaporated in vacuo, giving a dark-green solid. The crude
product thus obtained was recrystallized from CH2Cl2–
hexane (1:5, vol/vol) (several times) to provide pure 9 as
stable single crystals (53 mg, 126.0 mmol, 94% yield).
˚
(l¼0.71069 A, rotating anode: 50 kV, 180 mA) at
296 K. The structure was solved by direct methods
(SIR97) and expanded using Fourier techniques (DIR-
DIF94). The non-hydrogen atoms were refined aniso-
tropically. Hydrogen atoms were included but not refined.
The final cycle of full-matrix least-squares refinement was
based on F 2. All calculations were performed using the
teXsan crystallographic software package. CCDC No.:
228482.
Compound 9. Dark-green plates, mp 226 8C [determined by
thermal analysis (TGA and DTA)] (lit.10 219–220 8C).
Found: C, 91.74; H, 8.97%. Calcd for C32H36: C, 91.37; H,
8.63%; Rf¼0.39 on silica-gel TLC (hexane–AcOEt–
benzene¼90:5:5, vol/vol/vol); UV–vis lmax (CH3CN) nm
(log 1), 232 (4.58), 264 (4.62), 329 (4.60), 454 (4.68), 480sh
(4.59) and 661 (3.13); IR nmax (KBr) cm21, 2954 and 948
(trans-CHvCH–); MALDI-TOF-MS (without any matrix
reagent), m/z 420 (Mþ, 100%); exact EI-MS (70 eV), found:
m/z 420.2832 (100%); calcd for C32H36: Mþ, m/z 420.2817.
1H NMR (C6D6), signals based on the two 3-guaiazulenyl
groups at d 1.20 (12H, d, J¼7.0 Hz, (CH3)2CH-70,700), 2.57
(6H, brd s, Me-10,100), 2.73 (2H, sept, J¼7.0 Hz, Me2CH-70,
700),0 2.93 (6H, s, Me-40,400), 6.56 (2H, d, 00 J¼11.0 Hz,
H-5 ,500), 6.99 (2H, 0d0 d, J¼11.0, 2.0 Hz, H-60,6 ), 7.97 (2H,
d, J¼2.0 Hz, H-80,8 ), 8.14 (2H, brd s, H-20,200) and a signal
Crystallographic data for 7: C31H33N (FW¼419.61), dark-
green prism [from ethyl acetate–methanol¼1:5 (vol/vol),
the crystal size, 0.40£0.40£0.60 mm3], triclinic, P21 (#2),
˚
˚
˚
a¼10.368(4) A, b¼13.765(4) A, c¼9.083(4) A, a¼
3
˚
101.98(3)8, b¼101.38(3)8, g¼95.14(3)8, V¼1231.5(8) A ,
Z¼2, Dcalcd¼1.132 g/cm3, m(Mo-Ka)¼0.64 cm21, scan
width¼(1.47þ0.30 tan u)8, scan mode¼v22u, scan
rate¼8.08/min, measured reflections¼5981, observed
reflections¼5670, no. of parameters¼289, R1¼0.064,
wR2¼0.202 and goodness of fit indicator¼1.58.
3.1.16. Preparation of a,a0-bis(3-guaiazulenyl-
methylium) bis(tetrafluoroborate) (8). To a solution of
commercially available guaiazulene (1a) (357 mg,
1.8 mmol) in acetic acid (3 mL) was added a solution of
commercially available glyoxal (40% aqueous solution,
70 mL, ca. 0.6 mmol) in acetic acid (4 mL) containing
tetrafluoroboric acid (42% aqueous solution, 0.3 mL). The
mixture was stirred at 25 8C for 1 h under aerobic
conditions, giving a precipitation of a dark-purple solid of
8, and then was centrifuged at 2.5 krpm for 1 min. The crude
product thus obtained was carefully washed with diethyl
ether, and was recrystallized from acetonitrile–diethyl ether
(1:5, vol/vol) (several times) to provide pure 8 as stable
crystals (350 mg, 0.59 mmol, 98% yield).
based on the –CHvCH– unit 0a0 t d 8.12 (2H, s, H-1,2); 13
C
NMR (C6D6), d 146.3 (C-40,4 ), 141.2 (C-8a0,8a00), 140.0
(C-70,700), 136.100(C-20,200), 134.6 0(0 C-60,600), 133.02 (C-80,800),
132.5 (C-3a0,3a ), 128.8 (C-30,3 ), 126.8 0(C-5 ,500), 126.1
(C-10,100), 125.2 (C-1,2), 37.7 (Me2CH-7 ,700), 28.3 (Me-
40,400), 24.2 ((CH3)2CH-70,700) and 12.9 (Me-10,100).
3.1.18. X-ray crystal structure of (E)-1,2-di(3-guaia-
zulenyl)ethylene (9). A total 3234 reflections with
2umax¼55.08 were collected on a Rigaku AFC-5R auto-
mated four-circle diffractometer with graphite mono-
˚
Compound 8. Dark-purple plates, mp .160 8C [decomp.,
chromated Mo-Ka radiation (l¼0.71069 A, rotating

M. Nakatsuji et al. / Tetrahedron 60 (2004) 5983–6000
5999
anode: 50 kV, 180 mA) at 296 K. The structure was solved
by direct methods (SIR97) and expanded using Fourier
techniques (DIRDIF94). The non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were included but
not refined. The final cycle of full-matrix least-squares
refinement was based on F 2. All calculations were
performed using the teXsan crystallographic software
package. CCDC No.: 203374.
(C-20,60), 133.0 (C-8000), 130.7 (C-3000), 129.7 (C-200,6000),
126.4 (C-1000), 125.77 (C-5000), 125.71 (C-2), 114.11 (C-30,5 ),
114.05 (C-300,500), 54.8 000(0 MeO-400), 54.6 (MeO-40), 38.1
(Me2CH-7000), 28.4 (C-3 ,40000), 24.2 ((CH3)2CH-7000), 21.9
(Me-4000) and 12.8 (Me-1000).
Acknowledgements
Crystallographic data for 9: C32H36 (FW¼420.64), dark-
green plate (the crystal size, 0.30£0.10£0.60 mm3), mono-
This work was partially supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Science, Sports and Culture, Japan.
˚
˚
clinic, C2/c (#15), a¼38.874(10) A, b¼5.33(1) A,
3
˚
˚
c¼12.677(7) A, b¼107.29(4)8, V¼2509(5) A , Z¼4,
Dcalcd¼1.113 g/cm3,
m(Mo-Ka)¼0.62 cm21
,
scan
width¼(1.42þ0.30 tan u)8, scan mode¼v22u, scan
rate¼8.08/min, measured reflections¼3234, observed
reflections¼1564, no. of parameters¼145, R1¼0.089,
wR2¼0.242 and goodness of fit indicator¼1.88.
References and notes
1. Takekuma, S.; Sasaki, M.; Takekuma, H.; Yamamoto, H.
Chem. Lett. 1999, 999–1000.
3.1.19. Reaction of 2-(3-guaiazulenyl)-1,1-bis(4-
methoxyphenyl)ethylene (3) with N-chlorosuccinimide
(NCS). To a solution of commercially available N-chloro-
succinimide (NCS) (16 mg, 120 mmol) in hexane (1.0 mL)
was added a solution of 2-(3-guaiazulenyl)-1,1-bis(4-
methoxyphenyl)ethylene (3) (52 mg, 119 mmol) in hexane
(3.0 mL) containing chloroform (1.0 mL). The mixture was
stirred at 25 8C for 24 h under argon and then evaporated in
vacuo. The residue thus obtained was carefully separated by
silica-gel column chromatography with hexane–ethyl
acetate–benzene (5:4:1, vol/vol/vol) as an eluant. The
starting material 3 (42 mg, 96 mmol, 81%) was recovered.
The crude product, 1,1-bis(4-methoxyphenyl)-2-{3-[5-(suc-
cinimidyl)guaiazulenyl]}ethylene (16), thus obtained was
recrystallized from methanol to provide pure 16 as stable
crystals (6 mg, 12 mmol, 10% yield). Similarly, the reaction
of 3 with NCS at 60 8C for 24 h under argon gave the same
result as the above reaction at 25 8C.
2. Takekuma, S.; Takata, S.; Sasaki, M.; Takekuma, H.
Tetrahedron Lett. 2001, 42, 5921–5924.
3. Takekuma, S.; Tanizawa, M.; Sasaki, M.; Matsumoto, T.;
Takekuma, H. Tetrahedron Lett. 2002, 43, 2073–2078.
4. Sasaki, M.; Nakamura, M.; Hannita, G.; Takekuma, H.;
Minematsu, T.; Yoshihara, M.; Takekuma, S. Tetrahedron
Lett. 2003, 44, 275–279.
5. Sasaki, M.; Nakamura, M.; Takekuma, H.; Minematsu, T.;
Yoshihara, M.; Takekuma, S. Tetrahedron 2003, 59,
505–516.
6. Nakamura, M.; Sasaki, M.; Takekuma, H.; Minematsu, T.;
Takekuma, S. Bull. Chem. Soc. Jpn. 2003, 76, 2051–2052.
7. Takekuma, S.; Sasaki, K.; Nakatsuji, M.; Sasaki, M.;
Minematsu, T.; Takekuma, H. Bull. Chem. Soc. Jpn. 2004,
77, 379–380.
8. Fraser, M.; Raid, D. H. J. Chem. Soc. 1963, 1421–1429.
9. Hu¨nig, S.; Scheutzow, D.; Friedrich, H. J. Angew. Chem. 1964,
76, 818.
Compound 16. Dark-green prisms, mp 157 8C [determined
by thrmal analysis (TGA and DTA)]. Found: C, 78.21; H,
6.82; N, 2.57%. Calcd for C35H35NO4: C, 78.77; H, 6.61; N,
2.62%; Rf¼0.20 on silica-gel TLC (hexane–AcOEt–
benzene¼5:4:1, vol/vol/vol); UV–vis lmax (CH3CN) nm
(log 1), 273 (4.52), 332 (4.41), 357 (4.33), 410 (4.24) and
642 (2.54); IR nmax (KBr) cm–1; 2959, 2835 (C–H), 1713
(CvO), 1605, 1508 (aromatic CvC) and 1246, 1030
(C–O); exact EI-MS (70 eV), found: m/z 533.2571 (Mþ,
100%); calcd for C35H35NO4: Mþ, m/z 533.2566. 1H NMR
(C6D6), signals based on the 3-[5-(succinimidyl)guaia-
zulenyl] group at d 1.12 (6H, d, J¼6.9 Hz, (CH3)2CH-7000),
10. Hu¨nig, S.; Ort, B. Liebigs Ann. Chem. 1984, 1905–1935.
11. Hu¨nig, S.; Ort, B. Liebigs Ann. Chem. 1984, 1936–1951.
12. Hu¨nig, S.; Ort, B. Liebigs Ann. Chem. 1984, 1959–1971.
13. 1a: UV–vis lmax (CH3CN) nm (log 1), 213 (4.10), 244 (4.39),
284 (4.61), 301sh (4.03), 348 (3.65), 365 (3.46), 600 (2.68),
648sh (2.61) and 721sh (2.20). 1H NMR (C6D6), ( 1.22 (6H, d,
J¼7.0 Hz, (CH3)2CH-7), 2.615 (3H, s, Me-4), 2.624 (3H, brd
s, Me-1), 2.83 (1H, sept, J¼7.0 Hz, Me2CH-7), 6.79 (1H, d,
J¼11.0 Hz, H-5), 7.22 (1H, dd, J¼11.0, 2.0 Hz, H-6), 7.31
(1H, d, J¼4.0 Hz, H-3), 7.69 (1H, d, J¼4.0 Hz, H-2) and 8.22
(1H, d, J¼2.0 Hz, H-8); 13C NMR (C6D6), ( 144.1 (C-4), 139.7
(C-7), 138.1 (C-8a), 137.2 (C-3a), 136.7 (C-2), 134.6 (C-6),
133.2 (C-8), 125.4 (C-1), 125.2 (C-5), 113.5 (C-3), 38.5
(Me2CH-7), 24.8 ((CH3)2CH-7), 24.0 (Me-4) and 13.0 (Me-1);
DPV (Ep), þ0.65 and 21.77 V; CV, þ0.69 (Epa) and 21.79
(E1/2) V under the same electrochemical conditions as 3.
14. Bouwstra, J. A.; Schouten, A.; Kroon, J. Acta Crystalogr.
1984, C40, 428–431.
000
1.90–2.05 (4H, m, H-3a,b0000,4a,b0000), 2.26 (3H, s, Me-1 ),
000
2.67 (1H, sept, J¼6.9 Hz, Me2CH-7000), 2.77 (3H, s, Me-4 ),
7.09 (1H, d, J¼1.7 Hz, H-6000), 7.37 (1H, brd s, H-2000), 7.81
(1H, d, J¼1.7 Hz, H-8000) and signals based on the 1,1-bis(4-
methoxyphenyl) groups at d 3.25 (3H, s, MeO-40), 3.32 (3H,
s, MeO-400), 6.74 (2H, ddd, J¼8.6, 2.5, 1.0 Hz, H-30,50), 6.80
(2H, ddd, J¼8.6, 2.5, 1.00Hz, H-300,500), 7.374 (2H, ddd,
J¼8.6, 2.5,001.0 Hz, H-20,6 ), 7.374 (2H, ddd, J¼8.6, 2.5,
1.0 Hz, H-2 ,600) and a signal based on the .CvCH– unit
at d 7.53 (1H, s, H-2); 13C NMR (C6D6), d 175.7 (C-20000,50000000),
159.7 (C-400), 159.3 (C-40), 144.4 (C-4000), 141.1 (C-8a 00),
141.0 (C-2000), 139.6 (C-7000), 138.8 (C-1), 137.02 (C-1 ),
135.4 (C-6000), 133.72 (C-3a000), 133.66 (C-1 ), 133.2
15. Muthiah, C.; Praveen Kumar, K.; Kumaraswamy, S.; Kumara
Swamy, K. C. Tetrahedron 1998, 54, 14315–14326.
16. Bachmann, W.; Moser, F. H. J. Am. Chem. Soc. 1932, 54,
1124–1133.
17. Jordan, V.; Schafer, J. M.; Levenson, A. S.; Liu, H.; Pease,
K. M.; Simons, L. A.; Zapf, J. W. Cancer Res. 2001, 61,
6619–6623.

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