Thermal cyclization of nonconjugated aryl-yne-carbodiimide furnishing a dibenzonaphthyridine derivative

Article abstract of DOI:10.1248/cpb.57.393

The reagent-free C²-C⁷ thermal cyclization of a nonconjugated aryl-yne-carbodiimide yielded a dibenzo- [b,g][1,8]naphthyridine derivative, whose congeners are known to possess fascinating pharmacological properties. This is the first heteroaromatic compound prepared by the thermal cycloaromatization of "nonconjugated" aryl-ynes.

Full text of DOI:10.1248/cpb.57.393

April 2009
Notes
Chem. Pharm. Bull. 57(4) 393—396 (2009)
393
Thermal Cyclization of Nonconjugated Aryl–Yne–Carbodiimide
Furnishing a Dibenzonaphthyridine Derivative
Hidenori KIMURA,*,1) Kohei TORIKAI, and Ikuo UEDA
The Institute of Scientific and Industrial Research, Osaka University; 8–1 Mihogaoka, Ibaraki, Osaka 567–0047, Japan.
Received October 7, 2008; accepted January 21, 2009; published online January 23, 2009
The reagent-free C2–C7 thermal cyclization of a nonconjugated aryl–yne–carbodiimide yielded a dibenzo-
[b,g][1,8]naphthyridine derivative, whose congeners are known to possess fascinating pharmacological proper-
ties. This is the first heteroaromatic compound prepared by the thermal cycloaromatization of “nonconjugated”
aryl–ynes.
Key words nonconjugated; aryl–yne carbodiimide; dibenzonaphthyridine; thermal cyclization; C2–C7
Conjugated enyne compounds have received considerable the action of phenyl isothiocyanate in refluxing acetone
attention in the broad field of chemistry, because of their (69%).35) Desulfurization of 8 by treatment with methane-
unique cyclization reactions affording aromatized products sulfonyl chloride (MsCl) in the presence of triethylamine
by way of radical intermediates capable of DNA cleavage.2—8) and 4-dimethylaminopyridine (DMAP)36) successfully fur-
To date, a number of polyenyne compounds, including both nished carbodiimide 1 (84%). As for AYC 2, the synthesis
natural2,4,7) and artificial products,3,7,8) have been synthesized was initiated with 2-aminobenzylalcohol 9. Oxidation of al-
to evaluate their reactivity and to develop more potent and cohol 9 with MnO2 into aldehyde, followed by addition of
selective antitumor agents, however, modification of the con- phenylethynyl magnesium bromide gave the secondary alco-
jugated enyne core structures has not been well investigated. hol 10 (65% for two steps). Amine 10 was converted to the
We focused on nonconjugated polyenyne systems and found corresponding carbodiimide 2, in an analogous sequence uti-
that nonconjugated aryl–ynes and aryl–yne–allenes undergo lized in the synthesis of 1, except for the additional step of
thermal cycloaromatization (CA) reactions9—14) while cleav- tetrahydropyranyl (THP) ether formation. AYCs 1 and 2 were
ing DNA.15—17) Thus, as a next goal, we set a reagent-free purified as rapidly as possible and stored at ꢀ20 °C to avoid
thermal isomerization of nonconjugated aryl–yne systems, decomposition.
which involves homolyses of carbon–nitrogen (C–N) unsatu-
rated bonds to afford useful azaaromatic compounds via a 1 was carried out first (Chart 2). Although AYC 1 was heated
domino radical reaction.18)
at 110 °C for 72 h, the only product was urea 13 (19%),
With the desired AYCs in hand, the thermal CA reaction of
As target polycyclic aromatic compounds, we focused on which might be generated through a slow hydrolysis of car-
dibenzonaphthyridine derivatives, which have never been bodiimide 1 by a trace amount of water contaminated in the
synthesized via thermal isomerization of aryl–ynes, despite reaction, with a recovery of most of the starting material 1.
their fascinating and intriguing pharmacological proper-
ties.19—23) In order to provide a novel synthetic methodology
of dibenzonaphthyridines, we planned to examine the CA
reactions of nonconjugated aryl–yne–carbodiimides (AYCs).
Carbodiimide is considered to be an aza-equivalent of allene,
and more importantly, canceled dipole moments of C–N
bonds are expected to facilitate the homolytic cleavage of the
C–N bond to form radical species. The Wang24—28) and the
Schmittel29—31) groups have recently reported the thermal CA
of AYCs, but their scopes are limited to conjugated systems,
whose electronic and steric environments are far different
from nonconjugated ones, and which would be unable to pro-
vide dibenzonaphthyridine derivatives. Herein, we report the
synthesis and the CA reactions of AYCs 1 and 2.
Fig. 1. Structures of Aryl–Yne–Carbodiimides 1 and 2
As AYC substrates, we selected two compounds (Fig. 1).
One possesses a conjugated aryl–yne and a dependent car-
bodiimide moiety (1) and the other is equipped with a conju-
gated aryl–carbodiimide and a dependent alkyne moiety (2).
Synthesis of AYC 1 commenced with 2-bromobenzyl-
amine hydrochloride 3 (Chart 1). After tert-butoxycarbonyl
(Boc) protection of 3 (98%), the resulting bromobenzene 4
was coupled with ethynylbenzene 5 under Sonogashira–Hagi-
hara conditions32,33) to give 6 in good yield (90%).34) After
removal of the Boc group with trifluoroacetic acid (TFA),
amine 7 was converted to the corresponding thiourea 8 by
Reagents and conditions: (a) Boc2O, NaHCO3, THF, H2O, rt, 4 h, 98%; (b)
Pd(PPh3)2Cl2, CuI, Ph3P, E t 3N, rt, 65 h; (c) TFA, benzene, rt, 2 h, then aq. NaHCO3,
89% (over 2 steps); (d) PhNCS, acetone, reflux, 24 h, 69%; (e) MsCl, Et3N, DMAP,
CH2Cl2, rt, 15 min, 84%; (f) MnO2, CH2Cl2, 0 °C, 1 h; (g) PhCꢀCMgBr, THF, 0 °C,
0.5 h, 65% (over 2 steps); (h) PhNCS, acetone, reflux, 24 h, 89%; (i) DHP, PPTS,
CH2Cl2, 35 °C, 3 h, 96%; (j) MsCl, Et3N, DMAP, CH2Cl2, rt, 15 min, 67%.
Chart 1
∗ To whom correspondence should be addressed. e-mail: hidenori-kimura@ds-pharma.co.jp
© 2009 Pharmaceutical Society of Japan

394
Vol. 57, No. 4
Chart 2. Thermal Reaction of Aryl–Yne–Carbodiimide 1
Chart 4. Hypothetical Mechanisms for the Thermal Cyclization of
Aryl–Yne–Carbodiimide 2
Chart 3. Thermal Cyclization of Aryl–Yne–Carbodiimide 2
Thus, we moved on to examining the CA reaction of AYC 2
(Chart 3).
thermal cyclization of 2 proceeded at mildly heated condi-
Notably, subjection of 2 to heating at 80 °C in toluene, tions (50 °C) in a reagent-free manner in good yield, the pres-
without any reagents, resulted in the smooth and clean for- ent route could potentially be a novel and useful synthetic
mation of 14 (70%), whose structure was unambiguously de- methodology for benzonaphthyridine derivatives whose con-
1
termined as a dibenzonaphthyridine derivative by H–1H geners are known to possess fascinating pharmacological
COSY and NOE experiments. Moreover, the CA reaction of properties. Further scope and limitation studies on thermal
2 proved to proceed even at 50 °C, in a retained yield cyclization of nonconjugated aryl–yne–carbodiimides would
(77%).37) Since conjugated AYCs tend to require higher tem- be disclosed elsewhere.
perature for their C2–C6 thermal cyclizations,24—31) this result
Experimental
implied a possibility that C2–C7 cyclization of nonconjugated
General Anhydrous dichloromethane and tetrahydrofuran (THF) were
AYCs proceeds more facilely than that of conjugated ones.
Although the reaction mechanism for the thermal cycliza-
tions of this class of compounds is still controversial,31) we
tentatively envisaged that the C2–C7 thermal cyclization of
nonconjugated AYC 2 provided dibenzonaphthyridine deriva-
tive 14 as a result of the following three steps (Chart 4); (i)
C2–C7 conjunction between alkyne and carbodiimide moi-
eties of 2 giving diradical species 15, (ii) subsequent ring
closure of 15 yielding tetracyclic closed-shell intermediate
16, (iii) spontaneous elimination of alcohol (THPOH) at the
benzylic position of 16 to render the aromaticity to the prod-
uct (14). However, an alternative electrocyclization mecha-
nism for the conversion of 2 to 16 (iꢁ) cannot be ruled out.
The reason why the CA reaction of 2 occurred much more
smoothly than that of 1 is unclear, but one of the reasons is
purchased from Kanto Chemical Co., Inc. and used without further drying.
Triethylamine was purchased from Nacalai Tesque Inc. and used as supplied.
Other solvents were dried over activated molecular sieves 4A. All other
chemicals were obtained from local venders, and used as supplied unless
otherwise stated. Analytical thin-layer chromatography (TLC) was per-
formed using E. Merck silica gel 60 F254 pre-coated plates (0.25-mm thick-
ness). For column chromatography, silica gel 60 (70—270 mesh ASTM,
Merck), or aluminum oxide 90 (Merck) were used. IR spectra were recorded
on a Shimadzu FT-IR-8300. NMR spectra were recorded on a JEOL JNM-
LA400 (400 MHz). Chemical shifts were reported in ppm from tetramethyl-
silane with reference to internal residual solvent [1H-NMR, CHCl3 (7.26),
CHD2OD (4.78); 13C-NMR, CDCl3 (77.0)]. The following abbreviations
are used to designate the multiplicities: sꢂsinglet, dꢂdoublet, tꢂtriplet,
qꢂquartet, mꢂmultiplet. Mass spectra were recorded on a JEOL JMS600
under FAB conditions using m-nitrobenzyl alcohol (NBA) as a matrix.
Synthesis of Carbodiimide 1 Carbamate (4): A solution of 2-bro-
mobenzyl amine hydrochloride 3 (1.11 g, 5.00 mmol), NaHCO3 (1.26 g,
15.0 mmol), di-t-butyl dicarbonate (1.31 g, 6.00 mmol) in wet THF
supposed to lie in the existence of the tetrahydropyranoxy (THF–waterꢂ10 ml : 10 ml) was stirred at room temperature for 4 h. The re-
sulting mixture was neutralized with 1 N HCl, and extracted with EtOAc.
The combined organic layer was washed with brine, dried over MgSO4 and
evaporated in vacuo. The residue was purified by silica gel column chro-
group at the benzylic position of 2, which enables a smooth
aromatization via the elimination of the corresponding alco-
hol.
matography (hexane–EtOAc) to give carbamate 4 (1.40 g, 98%) as a color-
1
Nonetheless, it is noteworthy that 14 is the first example of
an azaaromatic compound prepared by reagent-free “C2–C7”
thermal cyclization of “nonconjugated” AYCs, in contrast
to the well-known “C2–C6” cyclization of “conjugated”
AYCs.29—31) Moreover, compounds comprised of a dibenzo-
[b,g][1,8]naphthyridine system are reported to exhibit in-
triguing biological activities.21,22) Although a number of effi-
cient synthetic methods for dibenzo[b,g][1,8]naphthyridines
have been reported,38—41) the present method via the thermal
isomerization of nonconjugated AYCs may alternatively be
favored, because of the mildness of the conditions and the
simple short-step procedure, which lead to a higher total
yield of the product.
less oil. H-NMR (CDCl3) d: 1.45 (9H, s), 4.38 (2H, s), 5.07 (1H, s), 7.13
(1H, ddd, Jꢂ7.8, 7.3, 1.7 Hz), 7.29 (1H, ddd, Jꢂ7.3, 7.3, 1.0 Hz), 7.37 (1H,
dd, Jꢂ7.3, 1.7 Hz), 7.54 (1H, dd, Jꢂ7,8, 1.0 Hz). 13C-NMR (CDCl3) d: 27.3,
28.3, 44.8, 79.6, 85.1, 123.4, 127.6, 128.9, 130.0, 132.7, 146.7, 155.8.
Amine (7): Under argon atmosphere, to a solution of 4 (1.43 g,
5.00 mmol) and ethynylbenzene (1.37 ml, 12.5 mmol) in triethylamine
(40 ml) was added bis(triphenylphosphine)palladium(II) dichloride (175 mg,
0.250 mmol), cupper(I) iodide (47.6 mg, 0.250 mmol), and triphenylphos-
phine (131 mg, 0.500 mmol) at room temperature. After being stirred at
room temperature for 65 h, the mixture was neutralized with 2 N HCl, diluted
with EtOAc, filtered through a pad of celite, and the filtrate was washed with
brine, dried over MgSO4, and the solvent was removed in vacuo. The residue
was roughly purified by alumina column chromatography (hexane–EtOAc)
to give phenyl ethynyl benzene 6 (1.39 g), which was used in the next reac-
tion without further purification.
To a solution of the above crude ethynyl benzene 6 in benzene (40 ml)
was added trifluoroacetic acid (7 ml), and the mixture was stirred at room
temperature for 2 h. The resulting mixture was neutralized with saturated aq.
In conclusion, we have demonstrated that the thermal cy-
cloaromatization of nonconjugated aryl–yne–carbodiimide 2
affords dibenzonaphthyridine 14, while 1 was inert. Since the NaHCO3 and extracted with EtOAc. The combined organic layer was

April 2009
395
137.1, 179.9, 180.0. IR (CHCl3) cmꢀ1: 3302, 3150, 2225, 1510. FAB-MS
m/z: 443 (MꢃH)ꢃ.
washed with brine, dried over MgSO4, and evaporated in vacuo. The residue
was purified by alumina column chromatography (EtOAc) to give amine 7
(930 mg, 89% for two steps), as a colorless solid. 1H-NMR (CD3OD) d: 4.38
(2H, s), 7.40—7.43 (3H, m), 7.45—7.54 (3H, m), 7.57—7.67 (3H, m).
Thiourea (8): Under argon atmosphere, to a solution of amine 7 (440 mg,
2.12 mmol) in acetone (5 ml) was added dropwise phenyl isothiocyanate
(0.25 ml, 2.1 mmol) at room temperature. After being stirred under reflux for
24 h, the reaction mixture was evaporated under reduced pressure, and the
residue was purified by silica gel column chromatography (hexane–EtOAc)
Carbodiimide (2): Carbodiimide 2 was prepared from 12 (315 mg,
0.711 mmol) in 67% yield, by a procedure similar to that employed for com-
pound 1. 1H-NMR (CDCl3) d: 1.26—1.83 (6H, m), 3.60 (1H, m), 3.94
(1/2H, t, Jꢂ7.8 Hz), 4.13 (1/2H, t, Jꢂ7.8 Hz), 4.78 (1/2H, m), 5.33 (1/2H,
m), 6.12 (1/2H, s), 6.17 (1/2H, s), 7.14—7.29 (11H, m), 7.44 (1H, ddd,
Jꢂ7.6, 6.7, 1.0 Hz), 7.45 (1H, dd, Jꢂ6.7, 1.0 Hz), 7.74 (1/2H, dd, Jꢂ7.6,
1.0 Hz), 7.82 (1/2H, dd, Jꢂ7.6, 1.0 Hz). 13C-NMR (CDCl3) d: 18.8, 19.1,
25.1, 25.3, 30.2, 30.7, 61.8, 62.0, 63.0, 64.2, 67.9, 71.6, 85.8, 86.6, 86.8,
87.9, 95.3, 96.8, 122.6, 122.8, 122.9, 124.2, 125.0, 125.4, 125.5, 125.9,
128.1, 128.1, 128.2, 128.3, 128.5, 128.7, 129.1, 129.2, 129.3, 129.4, 130.0,
1
to give thiourea 8 (501 mg, 69%) as a colorless solid. H-NMR (CDCl3) d:
5.04 (2H, s), 6.78 (1H, s), 7.06 (1H, ddd, Jꢂ7.8, 7.8, 1.0 Hz), 7.13—7.20
(4H, m), 7.23—7.31 (5H, m), 7.35—7.37 (2H, m), 7.45 (1H, dd, Jꢂ7.3,
1.0 Hz), 7.50 (1H, dd, Jꢂ7.3, 1.0 Hz), 8.77 (1H, s). 13C-NMR (CDCl3) d:
47.9, 86.8, 97.4, 122.2, 122.3, 124.7, 127.6, 128.2, 128.4, 128.5, 129.0,
129.8, 131.4, 132.1, 135.9, 138.8, 180.0. FAB-MS m/z: 343 (MꢃH)ꢃ.
Carbodiimide (1): At 0 °C under argon atmosphere, to a solution of
thiourea 8 (241 mg, 0.704 mmol), triethylamine (0.30 ml, 2.1 mmol), and 4-
dimethylamino pyridine (DMAP, 3 mg, 0.03 mmol) in dichloromethane
(7 ml) was added dropwise methanesulfonyl chloride (0.11 ml, 1.4 mmol).
After being stirred for 15 min at 0 °C, the mixture was filtered through a pad
of silica gel and the filtrate was concentrated in vacuo. The residue was puri-
fied by alumina column chromatography (hexane–EtOAc) to give carbodi-
130.5, 130.9, 131.8, 131.8, 136.0, 136.5, 138.1, 138.3. IR (CHCl3) cmꢀ1
:
2248, 2144. FAB-MS m/z: 409 (MꢃH)ꢃ.
Thermal Cycloaromatization of Carbodiimide
2 11-Phenyl-
dibenzo[b,g][1,8]naphthyridine (14): A solution of carbodiimide 2 (87 mg,
0.21 mmol) in toluene (5 ml) was stirred at 50 °C for 5 h under argon atmo-
sphere. After being cooled to room temperature, the reaction solution was
concentrated under reduced pressure. The residue was purified by alumina
column chromatography (hexane–EtOAc) to give benzonaphthyridine deriv-
1
ative 14 (67 mg, 77%) as a red solid. H-NMR (CDCl3) d: 7.41 (1H, ddd,
Jꢂ8.8, 6.6, 1.1 Hz), 7.46 (1H, ddd, Jꢂ8.5, 6.6, 0.7 Hz), 7.53—7.56 (2H, m),
7.69—7.70 (3H, m), 7.75 (1H, dd, Jꢂ8.8, 1.1 Hz), 7.80 (1H, ddd, J ꢂ8.8,
6.6, 1.1 Hz), 7.81 (1H, ddd, Jꢂ9.2, 6.6, 1.1 Hz), 7.86 (1H, dd, Jꢂ8.5,
1.1 Hz), 8.35 (1H, dd, Jꢂ9.2, 0.7 Hz), 8.39 (1H, dd, Jꢂ8.8, 1.1 Hz), 8.77
(1H, s). 13C-NMR (CDCl3) d: 119.1, 124.7, 125.8, 125.9, 126.4, 126.8,
128.5, 128.7, 128.9, 130.0, 130.5, 130.7, 131.6, 132.0, 135.2, 137.7, 149.9,
152.7, 152.9, 152.9. IR (CHCl3) cmꢀ1: 1580. UV lmax (CH2Cl2) nm (log e):
275 (5.46). FAB-MS m/z: 307 (MꢃH)ꢃ.
1
imide 1 (182 mg, 84%) as a colorless solid. H-NMR (CDCl3) d: 4.78 (2H,
s), 6.99—7.04 (3H, m), 7.16 (2H, dd, Jꢂ7.3, 1.0 Hz), 7.25—7.35 (5H, m),
7.46—7.55 (4H, m). 13C-NMR (CDCl3) d: 49.1, 86.5, 94.5, 121.9, 122.7,
123.7, 124.7, 127.7, 127.8, 128.2, 128.4, 128.7, 129.1, 131.5, 132.2, 137.1,
139.2, 139.8. IR (CHCl3) cmꢀ1: 2103. FAB-MS m/z: 309 (MꢃH)ꢃ.
Synthesis of Carbodiimide 2 Alcohol (10): To a solution of 2-
aminobenzylalcohol 9 (1.80 g, 15.0 mmol) in dichloromethane (75 ml) was
added manganese(II) oxide (16 g, 0.59 mmol) at 0 °C. After being stirred
vigorously at 0 °C for 1 h, the suspension was filtered, and the filtrate was
concentrated in vacuo to give the corresponding aldehyde. On the other
hand, in another apparatus, under argon atmosphere, to a solution of ethynyl
benzene (4.1 ml, 38 mmol) in THF (100 ml) was added ethyl magnesium
bromide (1 M in THF, 33 ml, 33 mmol) at 0 °C. The reaction mixture was
stirred at 0 °C for 1 h to give phenylethynyl magnesium bromide solution. At
0 °C, under argon atmosphere, to the above solution of Grignard reagent was
added dropwise the solution of aldehyde in THF (100 ml). After being
stirred at 0 °C for 30 min, the reaction was quenched with saturated aq.
NH4Cl and diluted with EtOAc. The organic layer was separated, washed
with brine, dried over MgSO4, and evaporated in vacuo. The residue was pu-
rified by silica gel column chromatography (hexane–EtOAc) to give alcohol
Acknowledgments We are grateful to Masataka Nakanishi, Dr.
Tomikazu Kawano (our laboratory) and Dr. Patrick C. Reid (PeptiDream
Inc., Tokyo, Japan), for invaluable discussions. This paper is dedicated to
Prof. Tohru Fukuyama on the occasion of his 60th “Kanreki” birthday.
References and Notes
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1
10 (2.2 g, 65%) as a colorless solid. H-NMR (CDCl3) d: 2.57 (1H, br s),
4.27 (2H, br s), 5.71 (1H, s), 6.14 (1H, dd, Jꢂ8.0, 1.2 Hz), 6.80 (1H, ddd,
Jꢂ8.0, 7.6, 1.2 Hz), 7.17 (1H, ddd, Jꢂ8.0, 7.6, 1.2 Hz), 7.32—7.34 (3H, m),
7.49—7.51 (3H, m). 13C-NMR (CDCl3) d: 63.9, 87.3, 87.4, 116.9, 118.5,
122.3, 124.6, 128.0, 128.3, 129.7, 131.8, 145.1. IR (CHCl3) cmꢀ1: 3580,
3390, 2190. FAB-MS m/z: 233 (Mꢃ), 206 (MꢀOH)ꢃ.
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Thiourea (11): Thiourea 11 was prepared from amine 10 (223 mg,
1.00 mmol) in 89% yield by a procedure similar to that employed for com-
pound 8. H-NMR (CDCl3) d: 3.70 (1H, s), 5.73 (1H, s), 7.18 (1H, ddd,
Jꢂ7.5, 7.1, 1.0 Hz), 7.22—7.34 (8H, m), 7.35 (1H, ddd, Jꢂ8.1, 7.8, 1.5 Hz),
7.40 (2H, ddd, Jꢂ8.1, 7.8, 1.2 Hz), 7.62 (1H, dd, Jꢂ8.1, 1.5 Hz), 7.65 (1H,
dd, Jꢂ7.8, 1.5 Hz), 8.50 (1H, s), 8.56 (1H, s). 13C-NMR (CDCl3) d: 62.1,
86.6, 87.3, 121.8, 125.0, 126.7, 127.0, 127.8, 128.0, 128.3, 128.7, 129.2,
131.6, 135.1, 136.0, 136.3, 180.0. IR (CHCl3) cmꢀ1: 3274, 2231, 1539.
FAB-MS m/z: 359 (MꢃH)ꢃ, 341 (MꢀOH)ꢃ.
Tetrahydropyranyl Ether (12): To a solution of alcohol 11 (348 mg,
0.970 mmol) in dichloromethane (10 ml) was added 3,4-dihydro-2H-pyran
(DHP, 0.26 ml, 2.9 mmol), pyridinium p-toluenesulfonate (PPTS, 24 mg,
0.10 mmol) at 0 °C. After being stirred at 35 °C for 3 h, the reaction was
quenched with saturated aq. NaHCO3 and diluted with chloroform. The or-
ganic layer was separated, washed with brine, dried over MgSO4 and evapo-
rated in vacuo. The residue was purified by silica gel column chromatogra-
phy (hexane–EtOAc) to give tetrapyranyl ether 12 (412 mg, 96%) as a color-
less solid. 1H-NMR (CDCl3) d: 1.26—1.83 (6H, m), 3.49 (1H, m), 3.73
(1/2H, m), 3.90 (1/2H, m), 4.44 (1/2H, m), 4.94 (1/2H, m), 5.65 (1/2H, s),
5.73 (1/2H, s), 7.16—7.40 (10H, m), 7.51 (1H, ddd, Jꢂ7.6, 5.6, 1.2 Hz),
7.55 (1H, ddd, Jꢂ7.8, 5.6, 1.2 Hz), 7.60 (1H, dd, Jꢂ7.6, 1.0 Hz), 7.84 (1/2H,
dd, Jꢂ7.8, 1.0 Hz), 7.88 (1/2H, dd, Jꢂ7.8, 1.0 Hz), 8.61 (1/2H, s), 8.67
(1/2H, s), 8.85 (1H, s). 13C-NMR (CDCl3) d: 18.7, 19.6, 24.8, 25.0, 25.2,
29.8, 30.0, 30.5, 61.9, 62.7, 63.2, 66.0, 84.8, 86.0, 86.4, 87.6, 94.4, 95.1,
96.5, 121.9, 122.1, 124.3, 125.4, 126.2, 126.9, 127.8, 128.0, 128.1, 128.3,
128.4, 128.6, 128.6, 128.7, 128.8, 129.1, 129.3, 129.5, 132.0, 136.4, 137.0,
1
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