Synthesis of 3-aryl-2-methoxyinden-1-one (Z)-phenylhydrazones via hydrobromic acid-mediated cyclization of 2-(1-aryl-2-methoxyethenyl)benzaldehyde phenylhydrazones

Article abstract of DOI:10.1002/hlca.201200277

2-(1-Aryl-2-methoxyethenyl)benzaldehydes 2, obtained by successive treatment of 1-(1-aryl-2-methoxyethenyl)-2-bromobenzenes 1 with BuLi and 1-formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH₂.

Full text of DOI:10.1002/hlca.201200277

Helvetica Chimica Acta – Vol. 96 (2013)
239
Synthesis of 3-Aryl-2-methoxyinden-1-one (Z)-Phenylhydrazones via
Hydrobromic Acid-Mediated Cyclization of 2-(1-Aryl-2-
methoxyethenyl)benzaldehyde Phenylhydrazones
by Kazuhiro Kobayashi*, Wataru Miyatani, and Naoki Matsumoto
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81-857-315263; e-mail: kkoba@chem.tottori-u.ac.jp)
2-(1-Aryl-2-methoxyethenyl)benzaldehydes 2, obtained by successive treatment of 1-(1-aryl-2-
methoxyethenyl)-2-bromobenzenes 1 with BuLi and 1-formylpiperidine, were transformed to the
corresponding phenylhydrazones 3 on treatment with PhNHNH2. When these hydrazones were allowed
to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3-aryl-2-
methoxyinden-1-one (Z)-phenylhydrazones 4.
Introduction. – In previous papers, we reported that the reactions of 1-lithio-2-(2-
methoxyethenyl)benzenes, generated from 1-bromo-2-(2-methoxyethenyl)benzenes
and BuLi, with various electrophiles, followed by conc. HI-mediated cyclization,
afforded fused heterocycles [1] and fused aromatics [2]. Herein, we wish to report that
the reaction of 1-(1-aryl-2-methoxyethenyl)-2-lithiobenzenes with 1-formylpiperidine
afforded 2-(1-aryl-2-methoxyethenyl)benzaldehydes 2, and that, interestingly, treat-
ment of the corresponding phenylhydrazones 3, derived from these aldehydes and
PhNHNH2, with conc. HI or HBr led to the formation of 3-aryl-2-methoxyinden-1-one
(Z)-phenylhydrazones 4. Although Hartke and Uhde reported the formation of 3-
acetyl-2-methoxyinden-1-one hydrazones by the treatment of 3-acetyl-2-methoxyin-
dene with diazo compounds [3a], there are no general methods for the preparation of
2-alkoxyinden-1-one hydrazones available [3].
Results and Discussion. – Our synthesis of 3-aryl-2-methoxyinden-1-one (Z)-
phenylhydrazones 4 was conducted as outlined in Scheme 1. 1-Bromo-2-(1-aryl-2-
methoxyethenyl)benzenes 1 were readily converted to 2-(1-aryl-2-methoxyethenyl)-
benzaldehydes 2 in fair-to-good yields on successive treatment with BuLi and 1-
formylpiperidine. The results are compiled in Table 1. Stereoisomers of each product
were generally separable by fractional column chromatography (CC) on SiO2, while
stereoisomers of compound 2c could not be separated (Entry 3), and (E)-2d was
obtained exclusively (Entry 4). The reason for this exclusive formation is unclear yet.
We initially investigated the possibility of the formation of 3,5-diphenyl-2,3-
benzodiazepine (5, R ¼ H, Ar¼ Ph) by a successive treatment of 2-(2-methoxy-1-
phenylethenyl)benzaldehyde (2a) with PhNHNH2 and conc. HI. Thus, compound (E)-
2a was treated with 1 equiv. of PhNHNH2 in MeCN at room temperature overnight.
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1
Table 1. Preparation of 2-(1-Aryl-2-methoxyethenyl)benzaldehydes 2
Entry
1
R
Ar
2
Yielda) [%]
(E)/(Z)b)
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
1g
H
H
H
H
H
H
Cl
Ph
2a
2b
2c
2d
2e
2f
2g
79
75
69
64
79
79
77
5 : 5c)
5 : 5c)
5 : 5d)
10 : 0
4-MeꢀC6H4
4-(t-Bu)ꢀC6H4
4-PhꢀC6H4
4-ClꢀC6H4
3-MeOꢀC6H4
Ph
6 : 4c)
6 : 4c)
5 : 5c)
a) Yields of isolated products. b) Approximate ratios. c) Separable by CC (SiO2). d) An inseparable
mixture.
The progress of the hydrazone formation was monitored by the disappearance of the IR
absorption band of the C¼O group of 2a. Subsequently, the resulting solution of the
corresponding hydrazone 3a was allowed to react with 1 equiv. of conc. HI at the same
temperature for 1 h. Aqueous workup, followed by purification by CC on SiO2 gave 2-
methoxy-3-phenylinden-1-one (Z)-phenylhydrazone (4a) in 34% yield as a red viscous
oil (Table 2, Entry 1) and not 5. The structure was determined on the basis of the
spectroscopic and analytical data given in the Exper. Part. The formation of 2-methoxy-
3-phenylindenone (6) by acid hydrolysis further clarified the structure of 4a
(Scheme 2). Diagnostic NOE enhancements between the MeO H-atoms and the NH
H-atom allowed unambiguous assignment of the configuration of 4a. To improve the
yield of 4a, conc. HBr was used in place of conc. HI. The reaction proceeded much
more cleanly to give 4a in a rather improved yield, though it is still modest (Entry 2).
The use of a smaller quantity of conc. HBr (0.5 equiv.) gave a poorer result (Entry 3).
The reaction of (E)-2a with 1 equiv. of conc. HCl yielded only a trace amount of the
desired product 4a (Entry 4). We next examined the reaction of (Z)-2a with 1 equiv. of
conc. HBr under the conditions mentioned above. Unfortunately, however, it resulted
in the formation of a considerably intractable mixture of products, and only 24% yield
of the desired product 4a was obtained (Entry 5).

Helvetica Chimica Acta – Vol. 96 (2013)
241
Table 2. Preparation of 3-Aryl-2-methoxy-1H-inden-1-one (1Z)-2-Phenylhydrazones 4
Entry
2
Acid (conc.)
equiv.
4
R
Ar
Yielda) [%]
1
2
3
4
5
6
7
8
9
(E)-2a
(E)-2a
(E)-2a
(E)-2a
(Z)-2a
(E)-2b
2c
(E)-2d
(E)-2e
(E)-2f
(E)-2g
HI
1
1
0.5
1
1
1
1
1
1
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
4g
H
H
H
H
H
H
H
H
H
H
Cl
Ph
Ph
Ph
Ph
34
50
29
< 1
24
47
31
55
54
31
50
HBr
HBr
HCl
HBr
HBr
HBr
HBr
HBr
HBr
HBr
Ph
4-MeꢀC6H4
4-(t-Bu)ꢀC6H4
4-PhꢀC6H4
4-ClꢀC6H4
3-MeOꢀC6H4
Ph
10
11
1
1
a) Yields of isolated products.
Scheme 2
The other six 2-(1-aryl-2-methoxyethenyl)benzaldehydes 2 were treated with conc.
HBr under the conditions in Entry 2 (see Exper. Part). Compounds (E)-2b, 2d, 2e, and
2g gave the desired products 4b, 4d, 4e, and 4g, respectively, in yields comparable to that
of 4a (Entries 6,8,9, and 11), while the yield of 4f was lower than those of the others
(Entry 10). The use of a mixture (E)-2c/(Z)-2c provided a poor result (Entry 7).
Although 4-chloro-2-(2-methoxy-1-phenylethenyl)benzaldehyde (2g) could be suc-
cessfully used in the present transformation to provide the corresponding desired
product 4g in a comparable yield (Entry 11), 4-methoxy-2-(2-methoxy-1-phenylethe-
nyl)benzaldehyde failed to give the desired product (data not shown). The reaction of
the hydrazone derived from this aldehyde with conc. HBr under the same conditions
resulted in the formation of an intractable mixture of products. While the details are
presently unclear, we would attribute this result and the lower yields of 4f to the
liability of the MeO substituents on the benzene nuclei to ether cleavage by HBr.
The formation of 3-aryl-2-methoxyinden-1-one (Z)-phenylhydrazones 4 from 2-(1-
aryl-2-methoxyethenyl)benzaldehyde phenylhydrazones 3 is assumed to proceed via
the intermediates depicted in Scheme 3. The hydrazones 3 are protonated to give the
iminium ion intermediates 7, which undergo intramolecular cyclization by the attack of
the alkene C-atom adjacent to the MeO substituent on the iminium C-atom to form the
stabilized bis-benzyl cation intermediates 8. In each of the intermediates 7, the attack of
the most nucleophilic center, the C-atom b to the MeO substituent, on the iminium C-
atom did not occur, because the formation of a four-membered ring is energetically
disfavored. Deprotonation from 8 gives 1-hydrazinoindene intermediates 9, which are

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Helvetica Chimica Acta – Vol. 96 (2013)
Scheme 3
then oxidized with air to give rise to 4. The electron-withdrawing Cl substituent did not
affect the yield of the products; the substrates (E)-2e and (E)-2g gave the products 4e
and 4g, respectively, in the yields comparable to those of others (Entries 9 and 11,
resp.).
In conclusion, we have shown that conc. HBr can mediate the formation of 3-aryl-2-
methoxyinden-1-one (Z)-phenylhydrazones 4 from the respective phenylhydrazones 3,
derived from 2-(1-aryl-2-methoxyethenyl)benzaldehydes 2 and PhNHNH2, in moder-
ate yields from (E)-2 and in low yields from (Z)-2. Further studies are under way in our
laboratory, to develop methods for the preparation of heterocyclic compounds utilizing
2.
Experimental Part
General. All of the org. solvents used in this study were dried over appropriate drying agents and
distilled prior to use. TLC: silica gel 60 PF254 (SiO2; Merck). Column chromatography (CC): Wako Gel
C-200E. M.p.: Laboratory Devices MEL-TEMP II melting-point apparatus; uncorrected. IR Spectra:
Shimadzu FTIR-8300 spectrophotometer; ˜n in cmꢀ1. NMR Spectra: JEOL ECP500 FT NMR
spectrometer (1H: 500 and 13C: 125 MHz), JEOL LA400 FT NMR spectrometer (1H: 400 and 13C:
100 MHz); in CDCl3; d in ppm rel. to Me4Si as internal standard, J in Hz. LR-EI-MS (70 eV): JEOL JMS
AX505 HA spectrometer; in m/z.
1-(1-Aryl-2-methoxyethenyl)-2-bromobenzenes 1a [4], 1b [2], 1c [4], 1d [2], 1e [4], and 1f [2] were
prepared by appropriate reported procedures. BuLi was supplied by Asia Lithium Corporation. All other
chemicals used in this study were commercially available.
1-Bromo-4-chloro-2-(2-methoxy-1-phenylethenyl)benzene (1g) was prepared from 2-bromo-5-chloro-
benzaldehyde as described in [2]. The reaction of PhMgBr with 2-bromo-5-chlorobenzaldehyde gave (2-
bromo-5-chlorophenyl)phenylmethanol. Yield: 92%. Colorless oil. Rf (AcOEt/hexane 1:10) 0.29. IR
(neat): 3310. 1H-NMR (500 MHz): 2.83 (s, 1 H); 6.02 (s, 1 H); 7.08 (dt, J ¼ 8.6, 2.9, 1 H); 7.24 – 7.34 (m,
5 H); 7.39 (dd, J ¼ 8.6, 2.9, 1 H); 7.61 (t, J ¼ 2.9, 1 H). Anal. calc. for C13H10BrClO (297.57): C 52.47, H
3.39; found: C 52.31, H 3.42. The pyridinium chlorochromate (PCC) oxidation of this alcohol gave (2-
bromo-5-chlorophenyl)phenylmethanone. Yield: 91%. White solid. M.p. 89 – 918 (hexane/Et2O). IR
(KBr): 1642. 1H-NMR (500 MHz): 7.32 – 7.34 (m, 2 H); 7.48 (t, J ¼ 7.4, 2 H); 7.57 (d, J ¼ 8.0, 1 H); 7.63 (t,
J ¼ 7.4, 1 H); 7.80 (d, J ¼ 7.4, 2 H). Anal. calc. for C13H8BrClO (295.56): C 52.83, H 2.73; found: C 52.88, H
2.72. This ketone was allowed to react with (methoxymethyl)triphenylphosphorane to give (E)-1g/(Z)-
1g. Yield: 68% (ca. 1:1).
Data of (E)-1g. Colorless oil. Rf (AcOEt/hexane 1:20) 0.51. IR (neat): 1638. 1H-NMR (500 MHz):
3.82 (s, 3 H); 6.26 (s, 1 H); 7.15 – 7.19 (m, 2 H); 7.26 – 7.36 (m, 5 H); 7.50 (d, J ¼ 8.6, 1 H). Anal. calc. for
C15H12BrClO (323.61): C 55.67, H 3.74; found: C 55.54, H 4.01.
Data of (Z)-1g. Colorless oil. Rf (AcOEt/hexane 1:20) 0.43. IR (neat): 1634. 1H-NMR (500 MHz):
3.76 (s, 3 H); 6.66 (s, 1 H); 7.09 (d, J ¼ 8.0, 2 H); 7.15 (dd, J ¼ 8.6, 2.2, 1 H); 7.19 (t, J ¼ 7.4, 1 H); 7.23 – 7.27
(m, 3 H); 7.56 (d, J ¼ 8.6, 1 H). Anal. calc. for C15H12BrClO (323.61): C 55.67, H 3.74; found: C 55.42, H
3.92.

Helvetica Chimica Acta – Vol. 96 (2013)
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2-(2-Methoxy-1-phenylethenyl)benzaldehyde (2a). Representative Procedure. To a stirred soln. of 1a
(1.7 g, 5.9 mmol) in THF (12 ml) at ꢀ 788 was added BuLi (1.6m soln. in hexane; 5.9 mmol) dropwise.
After 1 h, 1-formylpiperidine (0.80 g, 7.1 mmol) was added, and the temp. was gradually raised to 08. The
reaction was quenched by adding sat. aq. NH4Cl (15 ml), and the mixture was extracted with Et2O (3 ꢁ
15 ml). The combined extracts were washed with brine, dried (Na2SO4), and concentrated by
evaporation. The residue was purified by CC (SiO2) to give (E)-2a (0.56 g, 41%) and (Z)-2a (0.54 g,
38%).
Data of (E)-2a. Pale-yellow oil. Rf (THF/hexane 1:15) 0.39. IR (neat): 2839, 2747, 1694, 1640.
1H-NMR (500 MHz): 3.84 (s, 3 H); 6.20 (s, 1 H); 7.19 (t, J ¼ 7.3, 1 H); 7.29 (dd, J ¼ 7.8, 7.3, 2 H); 7.33 (d,
J ¼ 7.8, 1 H); 7.39 (d, J ¼ 7.8, 2 H); 7.44 (dd, J ¼ 7.8, 7.3, 1 H); 7.56 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.96 (d, J ¼
7.8, 1 H); 10.09 (s, 1 H). Anal. calc. for C16H14O2 (238.28): C 80.65, H 5.92; found: C 80.64, H 5.92.
Data of (Z)-2a. Pale-yellow oil. Rf (THF/hexane 1:15) 0.27. IR (neat): 2842, 2749, 1694, 1632.
1H-NMR (500 MHz): 3.71 (s, 3 H); 6.78 (s, 1 H); 7.15 (dd, J ¼ 7.8, 1.4, 2 H); 7.22 – 7.29 (m, 4 H); 7.43 (dd,
J ¼ 7.8, 7.3, 1 H); 7.58 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.99 (d, J ¼ 7.8, 1 H); 10.07 (s, 1 H). Anal. calc. for
C16H14O2 (238.28): C 80.65, H 5.92; found: C 80.60, H 5.90.
2-[2-Methoxy-1-(4-methylphenyl)ethenyl]benzaldehyde (2b). Data of (E)-2b. Yellow oil. Rf (THF/
1
hexane 1:15) 0.31. IR (neat): 2842, 2749, 1694, 1628. H-NMR (500 MHz): 2.32 (s, 3 H); 3.82 (s, 3 H);
6.16 (s, 1 H); 7.10 (d, J ¼ 8.2, 2 H); 7.28 (d, J ¼ 8.2, 2 H); 7.31 (d, J ¼ 7.8, 1 H); 7.42 (dd, J ¼ 7.8, 7.3, 1 H);
7.55 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.95 (d, J ¼ 7.8, 1 H); 10.08 (s, 1 H). Anal. calc. for C17H16O2 (252.31): C
80.93, H 6.39; found: C 80.83, H 6.41.
Data of (Z)-2b. Yellow oil. Rf (THF/hexane 1:15) 0.22. IR (neat): 2839, 2747, 1694, 1636. 1H-NMR
(500 MHz): 2.32 (s, 3 H); 3.69 (s, 3 H); 6.74 (s, 1 H); 7.04 (d, J ¼ 8.2, 2 H); 7.09 (d, J ¼ 8.2, 2 H); 7.22 (d,
J ¼ 7.8, 1 H); 7.42 (dd, J ¼ 7.8, 7.3, 1 H); 7.57 (ddd, J ¼ 7.8, 7.3, 0.9, 1 H); 7.99 (d, J ¼ 7.8, 1 H); 10.06 (s, 1 H).
Anal. calc. for C17H16O2 (252.31): C 80.93, H 6.39; found: C 80.80, H 6.41.
2-{1-[4-(1,1-Dimethylethyl)phenyl]-2-methoxyethenyl}benzaldehyde (2c). Yellow oil. A mixture of
stereoisomers (ca. 1:1). Rf (THF/hexane 1:15) 0.43. IR (neat): 2839, 2742, 1694, 1634. 1H-NMR
(500 MHz): 1.295 (s, 4.5 H); 1.301 (s, 4.5 H); 3.69 (s, 1.5 H); 3.83 (s, 1.5 H); 6.16 (s, 0.5 H); 6.76 (s, 0.5 H);
7.08 (d, J ¼ 8.7, 1 H); 7.24 (d, J ¼ 7.8, 0.5 H); 7.28 – 7.34 (m, 3.5 H); 7.41 – 7.45 (m, 1 H); 7.55 (ddd, J ¼ 7.8,
7.3, 1.4, 0.5 H); 7.58 (ddd, J ¼ 7.8, 7.3, 1.4, 0.5 H); 7.96 (dd, J ¼ 7.8, 1.4, 0.5 H); 7.99 (dd, J ¼ 7.8, 1.4, 0.5 H);
10.06 (s, 0.5 H); 10.09 (s, 0.5 H). Anal. calc. for C20H22O2 (294.39): C 81.60, H 7.53; found: C 81.59, H 7.52.
(E)-2-[1-(1,1’-Biphenyl-4-yl)-2-methoxyethenyl]benzaldehyde (2d). Yellow oil. Rf (THF/hexane
1:15) 0.39. IR (neat): 2839, 2746, 1692, 1622. 1H-NMR (500 MHz): 3.87 (s, 3 H); 6.24 (s, 1 H); 7.33 (tt, J ¼
7.3, 1.4, 1 H); 7.37 (dd, J ¼ 7.8, 1.4, 1 H); 7.40 – 7.49 (m, 5 H); 7.53 (d, J ¼ 8.7, 2 H); 7.56 – 7.60 (m, 3 H); 7.98
(dd, J ¼ 7.8, 1.4, 1 H); 10.13 (s, 1 H). Anal. calc. for C22H18O2 (314.38): C 84.05, H 5.77; found: C 84.07, H
5.82.
2-[1-(4-Chlorophenyl)-2-methoxyethenyl]benzaldehyde (2e). Data of (E)-2e. Yellow oil. Rf (AcOEt/
hexane 1:10) 0.26. IR (neat): 2841, 2746, 1691, 1631. 1H-NMR (500 MHz): 3.85 (s, 3 H); 6.23 (s, 1 H); 7.26
(d, J ¼ 8.6, 2 H); 7.31 (dd, J ¼ 7.4, 1.1, 1 H); 7.33 (d, J ¼ 8.6, 2 H), 7.46 (ddd, J ¼ 8.0, 7.4, 1.1, 1 H); 7.58 (td,
J ¼ 7.4, 1.7, 1 H); 7.96 (dd, J ¼ 8.0, 1.7, 1 H); 10.06 (s, 1 H). Anal. calc. for C16H13ClO2 (272.73): C 70.46, H
4.80; found: C 70.41, H 4.90.
Data of (Z)-2e. Yellow oil. Rf (AcOEt/hexane 1:10) 0.20. IR (neat) 2841, 2749, 1694, 1632. 1H-NMR
(500 MHz): 3.72 (s, 3 H); 6.77 (s, 1 H); 7.07 (d, J ¼ 7.2, 2 H); 7.19 (dd, J ¼ 7.2, 1.0, 1 H); 7.23 (d, J ¼ 7.2,
2 H); 7.44 (t, J ¼ 6.3, 1 H); 7.59 (ddd, J ¼ 7.2, 6.3, 1.0, 1 H); 8.00 (d, J ¼ 6.8, 1.0, 1 H); 10.04 (s, 1 H). Anal.
calc. for C16H13ClO2 (272.73): C 70.46, H 4.80; found: C 70.43, H 4.80.
2-[2-Methoxy-1-(3-methoxyphenyl)ethenyl]benzaldehyde (2f). Data of (E)-2f. Yellow oil. Rf
1
(AcOEt/hexane 1:15) 0.31. IR (neat): 2839, 2746, 1694, 1631. H-NMR (500 MHz): 3.76 (s, 3 H); 3.84
(s, 3 H); 6.21 (s, 1 H); 6.75 (dd, J ¼ 8.2, 2.3, 1 H); 6.91 (dd, J ¼ 7.8, 1.4, 1 H); 7.04 (dd, J ¼ 2.3, 1.8, 1 H);
7.21 (dd, J ¼ 8.2, 7.8, 1 H); 7.33 (dd, J ¼ 7.8, 0.9, 1 H); 7.43 (dd, J ¼ 7.8, 7.3, 1 H); 7.55 (ddd, J ¼ 7.8, 7.3, 1.4,
1 H); 7.96 (dd, J ¼ 7.8, 0.9, 1 H); 10.08 (s, 1 H). Anal. calc. for C17H16O3 (268.31): C 76.10, H 6.01; found: C
75.93, H 6.06.
Data of (Z)-2f. Yellow oil. Rf (AcOEt/hexane 1:15) 0.21. IR (neat): 2839, 2745, 1694, 1634. 1H-NMR
(500 MHz): 3.79 (s, 3 H); 3.82 (s, 3 H); 6.12 (s, 1 H); 6.83 (d, J ¼ 8.7, 2 H); 7.31 – 7.34 (m, 3 H); 7.43 (dd,

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Helvetica Chimica Acta – Vol. 96 (2013)
J ¼ 7.8, 7.3, 1 H); 7.55 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.95 (d, J ¼ 7.8, 1 H); 10.07 (s, 1 H). Anal. calc. for
C17H16O3 (268.31): C 76.10, H 6.01; found: C 75.95, H 6.17.
4-Chloro-2-(2-methoxy-1-phenylethenyl)benzaldehyde (2g). Data of (E)-2g. Yellow oil. Rf (AcOEt/
1
hexane 1:10) 0.40. IR (neat): 2843, 2751, 1693, 1636. H-NMR (500 MHz): 3.85 (s, 3 H); 6.23 (s, 1 H);
7.21 (t, J ¼ 7.4, 1 H); 7.31 (t, J ¼ 7.4, 2 H); 7.32 (d, J ¼ 1.7, 1 H); 7.37 (d, J ¼ 7.4, 2 H); 7.40 (dd, J ¼ 8.6, 1.7,
1 H); 7.89 (d, J ¼ 8.6, 1 H); 10.01 (s, 1 H). Anal. calc. for C21H13ClO2 (272.73): C 70.46, H 4.80; found: C
70.19, H 4.86.
Data of (Z)-2g. Yellow oil. Rf (AcOEt/hexane 1:10) 0.33. IR (neat): 2843, 2754, 1693, 1636.
1H-NMR (500 MHz): 3.72 (s, 3 H); 6.78 (s, 1 H); 7.14 (d, J ¼ 7.4, 2 H); 7.21 – 7.31 (m, 4 H); 7.39 (d, J ¼ 8.0,
1 H); 7.93 (d, J ¼ 8.0, 1 H); 9.99 (s, 1 H). Anal. calc. for C16H13ClO2 (272.73): C 70.46, H 4.80; found: C
70.40, H 4.85.
2-Methoxy-3-phenyl-1H-inden-1-one (1Z)-2-Phenylhydrazone (4a) Representative Procedure. To a
stirred soln. of (E)-2a (0.36 g, 1.5 mmol) in MeCN (3 ml) at r.t. was added PhNHNH2 (0.16 g, 1.5 mmol),
and stirring was continued overnight at the same temp. Then, conc. HBr (0.25 g, 1.5 mmol) was added,
and the mixture was stirred for an additional 1 h at the same temp. Sat. aq. NaHCO3 (10 ml) was added,
the mixture was extracted with AcOEt (3 ꢁ 10 ml), and the combined extracts were washed with brine
(10 ml) and dried (Na2SO4). After evaporation of the solvent, the residue was purified by CC (SiO2) to
1
give 4a (0.24 g, 50%). Red viscous oil. Rf (benzene/hexane 1:3) 0.50. IR (neat): 3325, 1601. H-NMR
(500 MHz): 3.61 (s, 3 H); 6.88 (tt, J ¼ 7.3, 1.4, 1 H); 6.93 – 6.97 (m, 1 H); 7.05 – 7.10 (m, 2 H); 7.19 (dd, J ¼
7.8, 1.4, 2 H); 7.25 (dd, J ¼ 7.8, 7.3, 2 H); 7.30 (tt, J ¼ 7.3, 1.4, 1 H); 7.38 (dd, J ¼ 7.8, 7.3, 2 H); 7.46 (dd, J ¼
7.8, 1.4, 2 H); 7.61 – 7.64 (m, 1 H); 10.52 (s, 1 H). 13C-NMR (125 MHz): 60.67; 113.33; 118.71; 118.84;
121.50; 123.47; 124.72; 127.16; 127.77; 128.41; 129.32; 129.45; 130.26; 133.42; 136.05; 139.59; 143.62;
149.09. MS: 326 (100, Mþ). Anal. calc. for C22H18N2O (326.39): C 80.96, H 5.56, N 8.58; found: C 80.93, H
5.82, N 8.41.
2-Methoxy-3-(4-methylphenyl)-1H-inden-1-one (1Z)-2-Phenylhydrazone (4b). Red solid. M.p. 132 –
1
1348 (hexane/AcOEt). IR (KBr): 3322, 1603. H-NMR (400 MHz): 2.42 (s, 3 H); 3.71 (s, 3 H); 6.96 (t,
J ¼ 7.3, 1 H); 7.04 – 7.06 (m, 1 H); 7.13 – 7.16 (m, 2 H); 7.26 – 7.29 (m, 4 H); 7.33 (dd, J ¼ 8.3, 7.3, 2 H); 7.44
(d, J ¼ 8.3, 2 H); 7.68 – 7.70 (m, 1 H); 10.59 (s, 1 H). 13C-NMR (100 MHz): 21.37; 60.59; 113.30; 118.69;
118.90; 121.43; 123.83; 124.71; 127.14; 129.14; 129.28; 129.31; 130.31; 130.37; 136.20; 137.63; 139.64;
143.69; 149.01. MS: 340 (100, Mþ). Anal. calc. for C23H20N2O (340.42): C 81.15, H 5.92, N 8.23; found: C
81.14, H 6.00, N 8.19.
3-[4-(1,1-Dimethylethyl)phenyl]-2-methoxy-1H-inden-1-one (1Z)-2-Phenylhydrazone (4c). Beige
oil. Rf (THF/hexane 1:15) 0.43. IR (neat): 3325, 1603. 1H-NMR (500 MHz): 1.31 (s, 9 H); 3.64 (s,
3 H); 6.89 (t, J ¼ 7.3, 1 H); 7.00 – 7.03 (m, 1 H); 7.07 – 7.10 (m, 2 H); 7.18 – 7.20 (m, 3 H); 7.26 (dd, J ¼ 7.8,
7.3, 1 H); 7.39 – 7.43 (m, 4 H); 7.61 – 7.64 (m, 1 H); 10.54 (s, 1 H). 13C-NMR (125 MHz): 14.07; 31.37;
50.67; 113.28; 118.66; 119.04; 121.40; 123.97; 124.69; 125.29; 127.11; 129.00; 129.30; 130.17; 130.39; 136.26;
139.59; 143.67; 148.99; 150.81. MS: 382 (100, Mþ). Anal. calc. for C26H26N2O (382.50): C 81.64, H 6.85, N
7.32; found: C 81.41, H 7.02, N 7.23.
3-(1,1’-Biphenyl-4-yl)-2-methoxy-1H-inden-1-one (1Z)-2-Phenylhydrazone (4d). Red solid. M.p.
156 – 1578 (hexane). IR (KBr): 3321, 1601. 1H-NMR (500 MHz): 3.77 (s, 3 H); 6.98 (t, J ¼ 7.3, 1 H); 7.12 –
7.14 (m, 1 H); 7.17 – 7.20 (m, 2 H); 7.28 (dd, J ¼ 7.8, 1.4, 2 H); 7.35 (t, J ¼ 7.3, 2 H); 7.39 (t, J ¼ 7.3, 1 H); 7.49
(dd, J ¼ 7.8, 7.3, 2 H); 7.64 (d, J ¼ 8.2, 2 H); 7.68 (dd, J ¼ 7.8, 1.4, 2 H); 7.70 – 7.73 (m, 3 H); 10.63 (s, 1 H).
13C-NMR (125 MHz): 60.80; 113.36; 118.77; 118.94; 121.56; 123.43; 124.83; 127.01; 127.07; 127.20; 127.52;
128.88 (two overlapped C-atoms); 129.34; 129.82; 130.38; 132.35; 136.08; 139.37; 140.53; 143.62; 149.27.
MS: 402 (100, Mþ). Anal. calc. for C28H22N2O (402.49): C 83.56, H 5.51, N 6.96; found: C 83.27, H 5.61, N
6.82.
3-(4-Chlorophenyl)-2-methoxy-1H-inden-1-one (1Z)-2-Phenylhydrazone (4e). Red viscous oil. Rf
1
(AcOEt/hexane 1:10) 0.71. IR (neat): 3323, 1603. H-NMR (400 MHz): 3.71 (s, 3 H); 6.96 – 7.01 (m,
2 H); 7.16 – 7.18 (m, 2 H); 7.27 (d, J ¼ 7.4, 2 H); 7.34 (t, J ¼ 7.4, 2 H); 7.44 (d, J ¼ 8.0, 2 H); 7.49 (d, J ¼ 8.0,
2 H); 7.70 – 7.71 (m, 1 H); 10.59 (s, 1 H). 13C-NMR (125 MHz): 60.77; 113.40; 118.64; 118.83; 121.71;
122.32; 124.93; 127.22; 128.75; 129.35; 130.20; 130.58; 130.74; 131.90; 135.72; 139.04; 143.51; 149.34. MS:
360 (100, Mþ). Anal. calc. for C22H17ClN2O (360.84): C 73.23, H 4.75, N 7.96; found: C 73.16, H 4.82, N
7.73.

Helvetica Chimica Acta – Vol. 96 (2013)
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2-Methoxy-3-(3-methoxyphenyl)-1H-inden-1-one (1Z)-2-Phenylhydrazone (4f). Red viscous oil. Rf
(AcOEt/hexane 1:10) 0.61. IR (neat): 3323, 1601. 1H-NMR (400 MHz): 3.73 (s, 3 H); 3.88 (s, 3 H); 6.91 –
6.98 (m, 2 H); 7.04 – 7.17 (m, 5 H); 7.24 – 7.28 (m, 2 H); 7.33 (dd, J ¼ 7.8, 7.3, 2 H); 7.38 (d, J ¼ 7.8, 1 H);
7.68 – 7.72 (m, 1 H); 10.60 (s, 1 H). 13C-NMR (100 MHz): 55.29; 60.60; 113.34; 113.50; 114.81; 118.71;
118.88; 121.53; 122.00; 123.28; 124.72; 127.19; 129.32; 129.44; 130.21; 134.75; 135.99; 139.53; 143.62;
149.09; 159.56. MS: 356 (100, Mþ). Anal. calc. for C23H20N2O2 (356.42): C 77.51, H 5.66, N 7.86; found: C
77.40, H 5.81, N 7.62.
5-Chloro-2-methoxy-3-phenyl-1H-inden-1-one (1Z)-2-Phenylhydrazone (4g). Red solid. M.p. 92 –
1
958 (hexane). IR (KBr): 3322, 1601. H-NMR (500 MHz): 3.72 (s, 3 H); 6.96 (s, 1 H); 6.99 (t, J ¼ 7.4,
1 H); 7.11 (d, J ¼ 8.0, 1 H); 7.27 (d, J ¼ 7.4, 2 H); 7.34 (t, J ¼ 7.4, 2 H); 7.40 (t, J ¼ 7.4, 1 H); 7.44 – 7.54 (m,
3 H); 7.60 (d, J ¼ 8.0, 1 H); 7.79 (d, J ¼ 8.0, 1 H); 10.61 (s, 1 H). 13C-NMR (100 MHz): 60.79; 113.47;
119.04; 119.65; 121.88; 124.34; 128.02; 128.30; 128.45; 128.55; 129.37; 129.52; 130.00; 132.88; 132.96;
134.82; 143.35; 149.83. MS: 360 (100, Mþ). Anal. calc. for C22H17ClN2O (360.84): C 73.23, H 4.75, N 7.76;
found: C 73.15, H 4.80, N 7.65.
2-Methoxy-3-phenyl-1H-inden-1-one (6) [5]. To a stirred soln. of 4a (30 mg, 0.090 mmol) in 1,2-
dimethoxyethane (2 ml) at r.t. was added 10% aq. HCl (1 ml). After stirring the mixture overnight at the
same temp., sat. aq. NaHCO3 (10 ml) was added. The org. materials were extracted with AcOEt (3 ꢁ
5 ml), and the combined extracts were washed with brine (10 ml) and dried (Na2SO4). After evaporation
of the solvent, the residue was purified by prep. TLC (SiO2) to give 6 (12 mg, 53%). Orange solid. M.p.
68 – 698 (hexane/Et2O) ([5]: m.p. 67 – 688). IR (neat): 1713, 1610. 1H-NMR (500 MHz): 3.96 (s, 3 H); 7.00
(d, J ¼ 7.4, 1 H); 7.10 (t, J ¼ 7.4, 1 H); 7.26 (td, J ¼ 7.4, 1.1, 1 H); 7.36 (d, J ¼ 7.4, 1 H); 7.41 (tt, J ¼ 7.4, 1.1,
1 H); 7.48 (t, J ¼ 7.4, 2 H); 7.59 (dd, J ¼ 7.4, 1.1, 2 H).
The authors thank Mrs. Miyuki Tanmatsu of our university for recording mass spectra and
performing combustion analyses.
REFERENCES
[1] K. Kobayashi, H. Hashimoto, T. Nagaoka, Y. Shirai, H. Konishi, Heterocycles 2010, 81, 699; K.
Kobayashi, D. Nakai, S. Fukamachi, H. Konishi, Heterocycles 2010, 81, 1703. See also refs. cit.
therein.
[2] K. Kobayashi, Y. Shirai, T. Nagaoka, H. Konishi, Synth. Commun. 2009, 39, 2866.
[3] a) K. Hartke, W. Uhde, Tetrahedron Lett. 1969, 1697; b) H. M. F. Madkour, Molecules 2000, 5, 737.
[4] K. Kobayashi, K. Hayashi, K. Miyamoto, O. Morikawa, H. Konishi, Synthesis 2006, 2934.
[5] C. F. Koelsch, J. Am. Chem. Soc. 1936, 58, 1321.
Received May 28, 2012