Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one and structural revision of the benzoindenone from Eichhornia crassipes

Article abstract of DOI:10.1515/znb-2018-0181

The total synthesis of the natural phytoalexin 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one (3) isolated from Eichhornia crassipes was accomplished in seven steps. The synthetic strategy included a Friedel-Crafts acylation and a Jacobsen-Katsuki epoxidation as the key reactions to obtain the target compound. Based on a comparison of the NMR data and a crystal structure of 3, the previously proposed structure of 2,5-dimethoxy-4-phenyl-benzoindenone (2) isolated from the same plant has been revised.

Full text of DOI:10.1515/znb-2018-0181

Z. Naturforsch. 2019; aop
Xiaowan Lia, Tongxu Sia, Chuenfai Ku, Hongjie Zhang, Mingzhong Wang* and Albert S.C. Chan
Synthesis of 2,6-dimethoxy-9-phenyl-1H-
phenalen-1-one and structural revision of
the benzoindenone from Eichhornia crassipes
https://doi.org/10.1515/znb-2018-0181
Received August 14, 2018; accepted October 2, 2018
high concentrations of anigorufone 1 (Fig. 1) and other
phenylphenalenones in the roots of nematode-infected
Musa resulted in resistance to the nematode Radopholus
Abstract: The total synthesis of the natural phytoalexin
similis. Compound 1 was identified to function as a strong
2,6-dimethoxy-9-phenyl-1H-phenalen-1-one (3) isolated
nematocidal compound by incorporating with lipids into
from Eichhornia crassipes was accomplished in seven
droplets throughout the body of the nematode, causing
steps. The synthetic strategy included a Friedel–Crafts
immobilization and eventual death [4]. Phenylphenal-
acylation and a Jacobsen–Katsuki epoxidation as the key
enone-type phytoalexins also show biological activities
reactions to obtain the target compound. Based on a com-
against various other pathogenic organisms [6–8].
parison of the NMR data and a crystal structure of 3, the
Eichhornia crassipes (water hyacinth) is a highly prob-
previously proposed structure of 2,5-dimethoxy-4-phenyl-
lematic, invasive species in freshwater habitats all over
benzoindenone (2) isolated from the same plant has been
the world, but this devastating aquatic weed was found
revised.
to be a good source of fungicides [9]. 2,5-Dimethoxy-
Keywords: benzoindenone; NMR; structural revision; 4-phenyl-benzoindenone 2 (Fig. 1), the first benzoinde-
synthesis; X-ray structure determination.
nonic compound to be discovered from E. crassipes, was
isolated by Della Greca et al. in 1991, who proposed the
structure shown in Fig. 1 [10]. The compound exhibited
moderate activity in inhibiting the growth of Candida albi-
cans. In search of potential allelochemical compounds
from E. crassipes, compound 3 (Fig. 1) was isolated and
its structure determined [11]. Recently, we found that the
NMR data of 2 highly matched with those of 3 [11]. The
originally assigned structure of 2 was found to be incor-
rect. Importantly, 3 has the 9-phenyl-phenalenone core
structure, which is the same as that of 1. Compounds 3
and 1 occur naturally as phytoalexins in plants, but they
are normally present only in very small amounts, which
limited their applications in agricultural and clinical uses.
Thus, there is the need for an independent synthesis and
further structure confirmation of 3.
1 Introduction
Phytoalexins are a group of secondary metabolites pro-
duced by plants in response to pathogen infections, pest
attacks, and abiotic stresses [1, 2]. They exhibit in vitro
or in vivo antimicrobial activity against a variety of phy-
topathogens. Therefore, it is possible to utilize them as
templates for synthesizing new pesticides [3]. Phenylphe-
nalenones, which are known as Musaceae phytoalexins
[4], are antifungal substances induced in banana (Masa
spp.) at the early stage of Mycosphaerella fijensis infec-
tion [5]. Recently, Hölscher and co-workers reported that
a
Xiaowan Li and Tongxu Si: These authors contributed equally to
this work.
2 Results and discussion
*Corresponding author: Mingzhong Wang, School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou
510006, PR China; and State Key Laboratory of Photochemistry and
Plant Resources in West China, Kunming Institute of Botany, Chinese
Academy of Sciences, Kunming 650201, PR China,
E-mail: mzwang2000@163.com
Xiaowan Li, Tongxu Si and Albert S.C. Chan: School of
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou
510006, PR China
Here we describe the first total synthesis of 3 and the
revised chemical structure of 2 by comparison of its NMR
data with that of compound 3. In a retro-synthetic analy-
sis, 3 was considered to be synthesized from 6-methoxy-
9-phenyl-1H-phenalen-1-one (4) via a Yang–Finnegan
epoxidation and the ring-opening reaction between C-2
and C-3 and a methoxylation reaction. Compound 4 could
be synthesized from 6-methoxy-1H-phenalen-1-one (5) by
Michael addition with phenylmagnesium bromide and
Chuenfai Ku and Hongjie Zhang: School of Chinese Medicine, Hong
Kong Baptist University, 7 Baptist University Road, Kowloon Tong,
Hong Kong SAR, PR China
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ꢀꢀꢀꢁ
2ꢀ ꢀX. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipes
OCH3
OH
2
OCH3
O
O
2
3
1
3a
9b
6a
4
3b
O
1
H3CO
4
5
9a
3a
9
8
5
9
7
6
OCH3
Anigorufone (1)
2,6-Dimethoxy-9-phenyl-
2,5-Dimethoxy-4-phenyl
1H-phenalen-1-one (3)
-benzoindenone (2)
Fig. 1:ꢀChemical structures of compounds 1–3.
dehydrogenation with 2,3-dichloro-5,6-dicyano-1,4-ben- yield (Scheme 1), which in turn was followed by Michael
zoquinone (DDQ). Compound 5 could be prepared from annulation with phenylmagnesium bromide and dehydro-
6-bromo-1H-phenalen-1-one (6) with sodium methoxide genation with DDQ to afford 4 in 65% yield. With sufficient
through a nucleophilic substitution reaction. Based on amounts of 4 in hand, the focus was initially on a Yang–
our previous work on the synthesis of 2-hydroxy-8-(4- Finnegan epoxidation and ring-opening reactions as key
hydroxyphenyl)-1H-phenalen-1-one [12], the intermediate 6 processes to give 2-hydroxy-6-methoxy-9-phenyl-1H-phen-
could be synthesized from the aldehyde 7 by a Wittig reac- alen-1-one 8 (Scheme 2).
tion, saponification, and a Friedel–Crafts reaction (Fig. 2).
However, wewereunabletoobtain8usingthisreaction
We thus used commercially available 4-bromo- sequence, which previously had been used successfully to
1-naphthoic acid (7a) as the starting material to synthesize prepare hydroxyanigorufone [13]. Similar findings were
4-bromo-1-naphthaldehyde (7) by reduction with BH3, fol- also reported by Otálvaro et al. in the synthesis of lachnan-
lowed by oxidation with Dess–Martin periodinane (DMP) thocarpone [14]. Subsequently, several other hydroxy-
in 78% yield. The compound (E)-3-(4-bromonaphthalen- lation conditions were screened for the formation of 8.
1-yl)acrylic acid (7b) was synthesized by the Wittig reac- Unfortunately, all attempts to effect the epoxidation of 8
tion of 7 with carbethoxymethyl-triphenylphosphonium under various conditions (H2O2/Na2CO3, m-CPBA/NaHCO3,
+
−
bromide (Ph3P CH2CO2Et Br ), followed by saponification. etc.) failed. Referring to literature procedures [14], finally,
The acrylic acid 7c was converted to 6 in a one-pot reac- 4 was sequentially treated under catalysis with (S,S)-[N,N’-
tion by Friedel–Crafts acylation in 56% yield (Scheme 1).
bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine]
Compound 6 was subsequently reacted with sodium manganese(II) chloride (Mn-salen) with 4-phenylpyri-
methoxide and catalytic amounts of copper iodide through dine N-oxide and sodium hypochlorite (aq.) to promote a
a nucleophilic substitution in methanol to give 5 in 80% Jacobsen–Katsuki epoxidation, followed by a ring-opening
OCH3
O
O
Yang-Finnegan
epoxidation
Michael annulation
Dehydrogenation
Methoxylation
OCH3
OCH3
4
3
O
O
Nucleophilic
substitution
CHO
Wittig reaction
Friedel-Crafts
OCH3
Br
Br
5
Fig. 2:ꢀRetro-synthetic analysis toward compound 3.
6
7
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X. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipesꢂ ꢂ3
O
O
O
H
O
OH
Ph3P+CH2CO2Et Br−
THF, tBuOK, r.t.
87%
NaOH (aq.), 40 °C
2. HCl (aq.), r.t.
1.
1
1. BH3, THF, 0−25 °C
2. Dess-Martin
NaHCO3, CH2Cl2
78%
95%
4
Br
Br
Br
7a
7
7b
1
O
OH
O
O
3
10
CH3ONa, CuI, reflux
CH3OH, 80%
4 1. Oxalyl chloride, DMF
2. AlCl3, CH2Cl2, r.t.
56%
8
6
Br
OCH3
Br
5
7c
6
Scheme 1:ꢀSynthesis of 6-methoxy-1H-phenalen-1-one (5).
O
O
a. tBuOOH, Triton B
1. THF, PhMgBr
Toluene, −5 °C
b. H2O2, Na2CO3
2. DDQ, CH
2Cl2, 65%
c. m-CPBA, NaHCO3
OCH3
OH
OCH3
4
5
1. Mn-salen
O
NaOCl (aq.), CH2Cl2
2. PTSA, Toluene
60%
−O N+
Ph
OCH3
8
Scheme 2:ꢀSynthesis of compound 8.
process catalyzed by p-toluenesulfonic acid (PTSA) to the as-synthesized 3 suitable for X-ray diffraction were
afford 8 smoothly in moderate yield (60%) (Scheme 2). obtained from methanol/ethyl acetate, and their crystal
Finally, treatment of 8 with potassium carbonate and molecular structure were determined (Fig. 3; see
and iodomethane in DMF gave 3 in 90% yield through a Experimental for further details), which in turn confirmed
nucleophilic substitution reaction (Scheme 3). The physi- that the published structure of 2 was incorrect.
cal and spectroscopic data of the synthetic compound
3 were identical to those reported in the literature [11]
OCH3
OH
O
(Supplementary material).
O
On comparing the 1H and 13C NMR data of 2 (literature-
reported) with those of 3 (synthetic), it was found that
all NMR data of 2 were identical to those of 3. The posi-
tions of C-4, C-7, C-9, C-10, C-3a, C-3b, C-7a, and C-1′ in 2
were reassigned by 2D NMR (Figs. 3 and 4, Tables 1 and 2).
Furthermore, the structure of 3 was firmly established
DMF, K2CO3
CH3I, 90%
OCH3
3 (200 mg)
OCH3
8
also by X-ray structure determination. Single crystals of Scheme 3:ꢀSynthesis of compound 3 from 8.
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4ꢀ ꢀX. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipes
Table 2:ꢀComparison of 1H NMR data of synthesized 3 with
literature-reported data of 2 and 3 (CDCl3, δ in ppm, J in Hz).
a
b
OCH3
2
Position 3a
3b
2c
Δδ1 Δδ2
3`
O
3
1
3
6.82, s
6.80, s
6.83, s
–0.02 0.01
1`
3a
5`
4
5
4 (7)d
5 (6)
7 (9)
8
7.60, d (8.0) 7.58, d (8.0) 7.61, d (8.4) –0.02 0.01
6.89, d (8.0) 6.87, d (8.0) 6.90, d (8.4) –0.02 0.01
8.63, d (8.4) 8.61, d (8.4) 8.63, d (8.0) –0.02
7.57, d (8.4) 7.55, d (8.4) 7.57, d (8.0) –0.02
7.37, d (7.6) 7.35, d (7.6) 7.34–7.46, m –0.02
7.43, d (7.6) 7.41, d (7.6) 7.34–7.46, m –0.02
7.39, d (7.6) 7.38, d (7.6) 7.34–7.46, m –0.01
7.43, d (7.6) 7.41, d (7.6) 7.34–7.46, m –0.02
7.37, d (7.6) 7.35, d (7.6) 7.34–7.46, m –0.02
9a
9
8
9b
6a
6
7
OCH3
2′
3′
4′
Fig. 3:ꢀMolecular structure of 3 in the crystal (a) and carbon
numbering (b). Displacement ellipsoids are drawn at the 50%
probability level, and H atoms as spheres with arbitrary radii.
5′
6′
MeO-2
3.86, s
3.84, s
4.06, s
3.86, s
4.08, s
–0.02
–0.02
MeO-6 (5) 4.08, s
aLiterature data of 3 [11]; bData of 3 (this work); cLiterature data of 2
[10]; dHydrogen numbering of 2 is given in parentheses.
OCH3
OCH3
a
b
O
H
H
O
In summary, a concise and efficient strategy was
developed for the synthesis of 3 utilizing Friedel–Crafts
acylation and Jacobsen–Katsuki epoxidation as the key
reactions. The observed overall yield of 3 (seven steps,
starting from 7a) was 10.0%. This is the first report of the
synthesis and X-ray crystal structure of 3. Based on a com-
parison of the NMR and crystal structural data of 3, the
previously proposed structure of 2 [10] isolated from E.
crassipes was revised.
H
H
H
OCH3
OCH3
Fig. 4:ꢀKey HMBC (a) and NOESY (b) correlations of 3.
Table 1:ꢀComparison of 13C NMR data of synthesized 3 with
literature-reported data of 2 and 3 (CDCl3, δ in ppm).
Position
3a
3b
2c
Δδ1
Δδ2
0.1
3 Experimental section
1
179.8, C
152.1, C
111.9, CH
121.4, C
130.6, CH
104.6, CH
157.4, C
124.3, C
128.3, CH
130.6, CH
148.4, C
126.3, C
125.7, C
142.9, C
127.8, CH
128.1, CH
126.8, CH
128.1, CH
127.8, CH
55.4, CH3
55.8, CH3
179.8, C
152.1, C
112.0, CH
121.5, C
130.7, CH
104.7, CH
157.4, C
124.3, C
128.3, CH
130.6, CH
148.4, C
126.3, C
125.8, C
143.0, C
127.9, CH
128.1, CH
126.9, CH
128.1, CH
127.9, CH
55.4, CH3
55.9, CH3
179.8, C
152.1, C
112.0, CH
121.4, C
130.7, CH
104.7, CH
157.4, C
124.3, C
128.3, CH
130.7, CH
148.4, C
126.3, C
125.7, C
143.0, C
127.9, CH
128.1, CH
126.9, CH
128.1, CH
127.9, CH
55.4, CH3
55.9, CH3
2
3
0.1
0.1
0.1
0.1
3.1 Materials and measurements
3a (4)d
4 (7)
5 (6)
6 (5)
6a (10)
7 (9)
8
0.1
0.1
Commercially available reagents were used without
further purification. All reactions were conducted in
oven-dried (Tꢀ=ꢀ120°C) or flame-dried glassware under N2
atmosphere and at ambient temperature (Tꢀ=ꢀ20–25°C)
unless otherwise stated. All solvents were distilled prior
to use: THF, benzene, and toluene were distilled from
Na/benzophenone, and DMF, Et3N, and CH2Cl2 from
CaH2. All non-aqueous reactions were performed under
an atmosphere of nitrogen or argon using oven-dried
glassware and standard syringe-in-septa techniques.
Concentration under reduced pressure was performed
at 5–350 mbar. Melting points were measured with a
Stanford Research Systems apparatus (OptiMelt-100).
1H NMR spectra were recorded in CDCl3 (unless stated
otherwise) on a Bruker Avance 400 or 500 instrument
at 400 or 500 MHz (13C NMR spectra at 100 or 125 MHz).
9 (1′)
9a (7a)
9b (3b)
1′(3a)
2′
0.1
0.1
0.1
0.1
0.1
3′
4′
0.1
0.1
0.1
0.1
0.1
0.1
5′
6′
MeO-2
MeO-6 (5)
aLiterature data of 3 [11]; bData of 3 (this work); cLiterature data of 2
[10]; dCarbon numbering of 2 is given in parentheses.
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ꢁꢀꢀꢀ
X. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipesꢂ ꢂ5
Chemical shifts are reported as δ values referenced layer was concentrated and purified by chromatography
to TMS. Mass spectra were measured on ABI Q-star (EtOAc/hexanesꢀ=ꢀ1:10) to afford (E)-ethyl 3-(4-bromon-
Elite mass spectrometer. Thin-layer chromatography aphthalen-1-yl)acrylate as a colorless oil (yield 4.0 g, 87%).
(TLC) was carried out using precoated sheets (Qingdao 1H NMR (400 MHz, CHCl3): δꢀ=ꢀ8.33 (d, Jꢀ=ꢀ15.6 Hz, 1H),
silica gel 60-F250, 0.2 mm) which, after development, 8.21–8.26 (m, 2H), 7.93 (d, Jꢀ=ꢀ8.0 Hz, 1H), 7.83 (d, Jꢀ=ꢀ6.8 Hz,
were visualized under UV light at 254 nm. Column 1H), 7.72–7.75 (m, 2H), 6.63 (d, Jꢀ=ꢀ15.6 Hz, 1H). 13C NMR
chromatography was performed on Qingdao silica gel 60 (100 MHz, CHCl3): δꢀ=ꢀ167.2, 139.3, 131.8, 131.5, 131.1, 129.9,
(230–400 mesh ASTM). Yields refer to chromatographi- 128.1, 128.0, 127.1, 125.7, 124.1, 123.9, 122.9. HRMS ((+)-ESI):
+
cally purified compounds.
m/zꢀ=ꢀ305.0159 (calcd. 305.0172 for C15H14BrO2, [Mꢀ+ꢀH] ).
3.2 General procedure for the synthesis
of 3–8
3.2.3 (E)-3-(4-Bromonaphthalen-1-yl)acrylic acid (7c)
−1
NaOH (50.0 mL, 1 mol L ) was added to (E)-ethyl
3.2.1 4-Bromo-1-naphthaldehyde (7)
3-(4-bromonaphthalen-1-yl)acrylate (3.6 g, 12.0 mmol) that
was diluted with THF (50.0 mL). The mixture was stirred
−1
BH3 (40.0 mL, 1 mol L ) was added to a solution of 7a at 40°C for 15 h. Then THF was removed under vacuum,
(5.0 g, 20.0 mmol) in dry THF (50.0 mL) at 0°C, and the and the residue was extracted with CH2Cl2 (100.0 mL) and
mixture stirred at room temperature for 5 h. The reac- H2O (200.0 mL). The aqueous phase was acidified with
tion was quenched with a saturated aqueous solution concentrated HCl to give 7c (yield 3.1 g, 95%) as a white
of NH4Cl and concentrated under vacuum. The aqueous solid, which was collected by filtration and dried under
residue was extracted with EtOAc (3ꢀ×ꢀ200.0 mL). The reduced pressure; m.p. 255–257°C. 1H NMR (400 MHz, [D6]
combined organic layers were dried over Na2SO4 and DMSO): δꢀ=ꢀ8.33 (d, Jꢀ=ꢀ15.6 Hz, 1H), 8.21–8.26 (m, 2H), 7.93
concentrated under vacuum. The residue was used in (d, Jꢀ=ꢀ8.0 Hz, 1H), 7.83 (d, Jꢀ=ꢀ6.8 Hz, 1H), 7.72–7.75 (m, 2H),
the next step without purification. Dess–Martin reagent 6.63 (d, Jꢀ=ꢀ15.6 Hz, 1H). 13C NMR (100 MHz, [D6]DMSO):
(8.5 g, 20.0 mmol) and NaHCO3 (5.0 g, 60.0 mmol) were δꢀ=ꢀ167.2, 139.3, 131.8, 131.5, 131.1, 129.9, 128.1, 128.0, 127.1,
added to a solution of the residue in CH2Cl2 (150.0 mL) at 125.7, 124.1, 123.9, 122.9. HRMS ((+)-ESI): m/zꢀ=ꢀ274.9713
+
0°C. The reaction mixture was stirred at 0°C for 4 h, H2O (calcd. 274.9713 for C13H8BrO2, [M – H] ).
(200.0 mL) was added, and the mixture was extracted
with CH2Cl2 (3ꢀ×ꢀ200.0 mL). The combined organic layer
was concentrated under vacuum. The residue was puri- 3.2.4 6-Bromo-1H-phenalen-1-one (6)
fied by chromatography (EtOAc/hexanesꢀ=ꢀ1:20) to afford
the compound 7 (yield 3.6 g, 78%) as a colorless solid; To a solution of compound 7c (3.0 g, 11.5 mmol) in dry
1
m.p. 79–81°C. H NMR (400 MHz, CDCl3): δꢀ=ꢀ10.36 (s, 1H, CH2Cl2 (100.0 mL), oxalyl chloride (7.0 mL, 80.0 mmol)
–CHO), 9.27 (d, Jꢀ=ꢀ8.4 Hz, 1H, Ar-H), 8.35 (d, Jꢀ=ꢀ8.4 Hz, 1H, was added and the mixture stirred for 20 min. Then,
Ar-H), 7.95 (d, Jꢀ=ꢀ7.6 Hz, 1H, Ar-H), 7.79 (d, Jꢀ=ꢀ7.6 Hz, 1H, two drops of dry DMF were added, and the mixture was
13
Ar-H), 7.69–7.75 (m, 2H, Ar-H). C NMR (100 MHz, CDCl3): stirred overnight at room temperature. The light yellow
δꢀ=ꢀ192.6, 136.1, 132.1, 131.4, 131.3, 130.9, 129.8, 129.3, 128.3, solution was evaporated under vacuum to afford (E)-
127.7, 125.1. HRMS ((+)-ESI): m/zꢀ=ꢀ234.9731. (calcd. 234.9753 3-(4-bromonaphthalen-1-yl)acryloyl chloride, which was
+
for C11H7BrO, [Mꢀ+ꢀH] ).
rapidly dissolved in dry CH2Cl2 (100.0 mL). AlCl3 (2.4 g,
18.0 mmol) was added at 0°C, and stirred overnight at
25°C. The mixture was poured slowly onto ice, and the
aqueous phase was extracted with CH2Cl2 (2ꢀ×ꢀ200.0 mL).
The organic phase was combined and concentrated
3.2.2 (E)-Ethyl 3-(4-bromonaphthalen-1-yl)acrylate (7b)
To a solution of (carbethoxymethy1)triphenylphospho- under vacuum, and the residue was purified by chro-
nium bromide (9.2 g, 15.0 mmol) in 100 mL THF, BuOK matography on silica gel (petroleum ether/EtOAcꢀ=ꢀ9:1)
t
(2.3 g, 15.0 mmol) was added. The solution was stirred to afford 6 as an orange solid (yield 1.7 g, 56%); m.p.
for 2 h, compound 7 (3.5 g, 15.0 mmol) was added, and 177–179°C. 1H NMR (400 MHz, CDCl3): δꢀ=ꢀ8.64 (dd, Jꢀ=ꢀ7.2,
stirring continued for 15 h. The mixture was evaporated 1.2 Hz, 1H), 8.56 (dd, Jꢀ=ꢀ8.4, 1.2 Hz, 1H), 7.84 (t, Jꢀ=ꢀ8.4 Hz,
under reduced pressure, and the residue was extracted 2H), 7.67 (d, Jꢀ=ꢀ9.6 Hz, 1H), 7.52 (d, Jꢀ=ꢀ7.6 Hz, 1H), 6.72
with EtOAc (2ꢀ×ꢀ100.0 mL) and H2O (200.0 mL). The organic (d, Jꢀ=ꢀ9.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): δꢀ=ꢀ184.9,
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ꢀꢀꢀꢁ
6ꢀ ꢀX. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipes
141.3, 134.1, 131.1, 131.1, 131.1, 130.7, 129.6, 129.2, 128.7, EtOAcꢀ=ꢀ7:1) to afford 8 as a red solid (yield 300.0 mg,
128.2, 128.0, 127.6. HRMS ((+)-ESI): m/zꢀ=ꢀ280.9574 (calcd. 60%); m.p. 183–185°C. 1H NMR (400 MHz, CDCl3): δꢀ=ꢀ8.70
+
280.9572 for C13H7BrONa, [Mꢀ+ꢀNa] ).
(dd, Jꢀ=ꢀ8.4, 1.2 Hz, 1H), 7.64 (d, Jꢀ=ꢀ8.0 Hz, 1H), 7.58 (dd,
Jꢀ=ꢀ8.4, 1.2 Hz, 1H), 7.48 (ddd, Jꢀ=ꢀ10.4, 7.2, 3.6 Hz, 3H), 7.37
(dt, Jꢀ=ꢀ8.0, 1.2 Hz, 2H), 7.08 (d, Jꢀ=ꢀ1.2 Hz, 1H), 6.94–6.86
(m, 2H), 4.08 (s, 3H). 13C NMR (100 MHz, CDCl3): δꢀ=ꢀ179.9,
158.1, 149.2, 148.4, 142.6, 132.4, 130.3, 129.6, 128.2, 127.8,
3.2.5 6-Methoxy-9-phenyl-1H-phenalen-1-one (4)
A solution of 5 (840.0 mg, 4.0 mmol) in dry THF (50.0 mL) 127.5, 125.8, 124.5, 123.6, 121.5, 113.2, 105.1, 56.0. HRMS
was added slowly to the Grignard reagent (6.0 mmol, pre- ((+)-ESI): m/zꢀ=ꢀ303.1013 (calcd. 303.1016 for C20H15O3,
+
pared from 1-bromo-4-methoxybenzene and Mg in dry [Mꢀ+ꢀH] ).
THF) under nitrogen atmosphere. After stirring for 30 min
at –10°C, the mixture was allowed to warm up to 25°C and
stirred for 40 min. The mixture was quenched with HCl (aq., 3.2.7 2,6-Dimethoxy-9-phenyl-1H-phenalen-1-one (3)
5.0%) and extracted with EtOAc (2ꢀ×ꢀ100.0 mL), and the com-
bined organic phase was washed with H2O and evaporated To a solution of 8 (210.0 mg, 0.7 mmol) and K2CO3
to dryness. The crude material was diluted with CH2Cl2 (960.0 mg, 7.0 mmol) in DMF (15.0 mL) stirred for 1 h,
(100.0 mL) and treated with DDQ (2.0 equiv.), refluxed for CH3I (0.2 mL, 3.5 mmol) was added. The mixture was kept
2 h, and cooled to 25°C. The mixture was concentrated and stirred for 10 h at 25°C. Then the reaction was quenched
purified by chromatography on silica gel (petroleum ether/ with H2O (100.0 mL), extracted with EtOAc (2ꢀ×ꢀ100.0 mL),
EtOAcꢀ=ꢀ9:1) to afford 4 as an orange solid (yield 740.0 mg, and the combined organic extract evaporated to dryness.
two steps, 65%); m.p. 183–185°C. 1H NMR (400 MHz, CDCl3): The residue was separated and purified by chromatogra-
δꢀ=ꢀ8.58 (dd, Jꢀ=ꢀ8.4, 1.2 Hz, 1H), 7.66 (d, Jꢀ=ꢀ8.0 Hz, 1H), 7.56 phy on silica gel (petroleum ether/EtOAcꢀ=ꢀ9:1) to afford
(ddd, Jꢀ=ꢀ9.6, 8.0, 1.2 Hz, 2H), 7.51–7.39 (m, 2H), 7.37 (td, Jꢀ=ꢀ6.0, 3 as an orange solid (yield 200.0 mg, 90%); m.p. 183–
1
13
2.8 Hz, 3H), 6.88 (d, Jꢀ=ꢀ8.0 Hz, 1H), 6.47 (dd, Jꢀ=ꢀ9.6, 1.2 Hz, 185°C. H and C NMR (Tables 1 and 2). HRMS ((+)-ESI):
+
1H), 4.08 (s, 3H). 13C NMR (100 MHz, CDCl3): δꢀ=ꢀ185.8, 159.5, m/zꢀ=ꢀ317.1164 (calcd. 317.1172 for C21H17O3, [Mꢀ+ꢀH] ).
147.9, 143.2, 140.4, 133.1, 130.8, 129.4, 128.2, 127.9, 127.9, 127.0,
126.2, 124.5, 121.6, 104.4, 56.0. HRMS ((+)-ESI): m/zꢀ=ꢀ287.1063
+
(calcd. 287.1067 for C20H15O3, [Mꢀ+ꢀH] ).
3.3 Crystal structure determination of 3
The crystal and molecular structure of 3 were determined
by single-crystal X-ray diffraction. A suitable single crystal
was obtained from methanol/ethyl acetate and investi-
gated on an Xcalibur Onyx Nova diffractometer with the
3.2.6 2-Hydroxy-6-methoxy-9-phenyl-1H-phenalen-1-
one (8)
A solution of compound 4 (500.0 mg, 1.7 mmol), temperature kept at Tꢀ=ꢀ100(2) K during data collection.
(S,S)-[N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2- The structure was solved and refined using the programs
cyclohexanediamine]manganese(II) chloride (55.0 mg, XS and Olex2 [15], respectively. The program X-Seed [16]
0.08 mmol), and 4-phenylpyridine-N-oxide (72.0 mg, was used as an interface to the program Shelx [17, 18] to
0.4 mmol) in dichloromethane (100.0 mL) was cooled produce the molecular graphics.
to 0°C and treated by precooled sodium hypochlorite
Crystal data for 2,6-dimethoxy-9-phenyl-1H-phe-
(40.0 mL, 14.3 wt%). The mixture was stirred for 4 h at nalen-1-one (3): C21H16O3 (Mrꢀ=ꢀ316.3), tetragonal space
0°C. Formation of the epoxide was observed by TLC. The group I41/a (no. 88), aꢀ=ꢀbꢀ=ꢀ32.6613(5), cꢀ=ꢀ5.6505(1) Å,
reaction was quenched with saturated Na2S2O3 solution, Vꢀ=ꢀ6027.7(2) Å3, Zꢀ=ꢀ16, Tꢀ=ꢀ100(2) K, Cu Kα radiation
−1
−3
the mixture extracted with DCM (2ꢀ×ꢀ100.0 mL) and H2O (λꢀ=ꢀ1.54184 Å), μ(Cu Kα)ꢀ=ꢀ0.746 mm , dcalcdꢀ=ꢀ1.394 mg m ,
(200.0 mL), and the organic layer concentrated to give a 5403 measured reflections of which 2693 were unique
residue. The residue was diluted in toluene (100.0 mL), (Rintꢀ=ꢀ0.0195, Rsigmaꢀ=ꢀ0.0221) and were used in all calcula-
and p-toluenesulfonic acid monohydrate (0.65 g, tions. The final refinement gave R1ꢀ=ꢀ0.0350 (Iꢀ>ꢀ2 σ(I)) and
−3
3.4 mmol) was added, and the mixture was stirred over- wR2ꢀ=ꢀ0.0933 (all data), Δρfin (max/minꢀ=ꢀ–0.20/0.16 e Å ).
night. The mixture was concentrated and extracted with
CCDC 1812926 contains the supplementary crystallo-
EtOAc (2ꢀ×ꢀ100.0 mL) and H2O (200.0 mL). The organic graphic data for this paper. These data can be obtained
layer was concentrated, and the residue was purified by free of charge from the Cambridge Crystallographic Data
column chromatography on silica gel (petroleum ether/ Centre via www.ccdc.cam.ac.uk/data_request/cif.
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ꢁꢀꢀꢀ
X. Li et al.: Synthesis of 2,6-dimethoxy-9-phenyl-1H-phenalen-1-one from Eichhornia crassipesꢂ ꢂ7
[5] F. Echeverri, F. Torres, W. Quiñones, G. Escobar, R. Archbold,
Phytochem. Rev. 2012, 11, 1.
Acknowledgment: This work was financially supported
by the Research Foundation for Advanced Talents (36000-
18821101), Guangdong Natural Science Foundation
(2017A030313751), The Science and Technology Planning
Project of Guangzhou City (201707010189), The China
Postdoctoral Science Foundation (2018M640942), and
the Interdisciplinary Research Matching Scheme (RC-
IRMS/15-16/02) of Hong Kong Baptist University, Hong
Kong SAR, China.
[6] K. Jitsaeng, B. Schneider, Phytochem. Lett. 2010, 3, 84.
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F. Echeverri, R. Arango, B. Schneider, J. Nat. Prod. 2007, 70, 887.
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supplementary material (https://doi.org/10.1515/znb-2018-0181).
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Z. Naturforsch.ꢂ
ꢂ2019 | Volume x | Issue x(b)
Graphical synopsis
Xiaowan Li, Tongxu Si, Chuenfai Ku,
Hongjie Zhang, Mingzhong Wang
and Albert S.C. Chan
Synthesis of 2,6-dimethoxy-9-phenyl-
1H-phenalen-1-one and structural revision
of the benzoindenone from Eichhornia
crassipes
https://doi.org/10.1515/znb-2018-0181
Z. Naturforsch. 2019; x(x)b: xxx–xxx
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