Ultrasound-assisted convenient synthesis of hypolipidemic active natural methoxylated (E)-arylalkenes and arylalkanones

Article abstract of DOI:10.1016/j.tet.2005.01.071

An ultrasound-assisted convenient method was developed for the conversion of toxic methoxylated cis-isomer of arylalkenes into its hypolipidemic active trans-isomer. Treatment of cis-isomer or mixture of all three isomers (1a-1j) with ammonium formate and 10% Pd/C gave arylalkanes (2a-2j), which upon oxidation with DDQ in anhydrous dioxane containing a little amount of silica gel, provided (E)-arylalkenes (3a-3g) in 42-72% yield depending upon the substituents attached at the aryl ring. The same method, upon addition of a few drops of water, provided hypolipidemic active arylalkanones (3h-3j) in 59-65% yield.

Full text of DOI:10.1016/j.tet.2005.01.071

Tetrahedron 61 (2005) 3075–3080
Ultrasound-assisted convenient synthesis of hypolipidemic active
natural methoxylated (E)-arylalkenes and arylalkanones*
*
Bhupendra P. Joshi, Anuj Sharma and Arun K. Sinha
Natural Plant Products Division, Institute of Himalayan Bioresource Technology, Palampur, HP 176061, India
Received 12 November 2004; revised 7 January 2005; accepted 20 January 2005
Abstract—An ultrasound-assisted convenient method was developed for the conversion of toxic methoxylated cis-isomer of arylalkenes
into its hypolipidemic active trans-isomer. Treatment of cis-isomer or mixture of all three isomers (1a–1j) with ammonium formate and 10%
Pd/C gave arylalkanes (2a–2j), which upon oxidation with DDQ in anhydrous dioxane containing a little amount of silica gel, provided
(E)-arylalkenes (3a–3g) in 42–72% yield depending upon the substituents attached at the aryl ring. The same method, upon addition of a few
drops of water, provided hypolipidemic active arylalkanones (3h–3j) in 59–65% yield.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the above methods result in formation of some amount of
unwanted toxic14 cis-isomer15 along with the desired trans-
isomer and it becomes difficult to separate them through
column purification16 due to resemblance in Rf values of
both the isomers. Recent development of disodium iron
tetracarbonyl, iridium and palladium(II) catalyzed isomer-
ization of gamma17 and cis-arylalkenes18 is a very useful
entry to (E)-arylalkene synthesis. However, expensive
reagents limit its scope for a large scale synthesis. As for
the synthesis of aforementioned hypolipidemic aryl-
alkanones 3h–3j, a lot of methods19 are reported which
mainly involve Grignard10 and Friedel–Crafts7 approaches.
Overall, all the synthetic methods mentioned above suffer
from some drawbacks such as long reaction time, tedious
workups, expensive and hazardous reagents and starting
materials. Keeping this in mind, it would, therefore, be
useful to utilize inexpensive and abundantly available
isomeric mixture of arylalkenes in a reliable, mild,
economical and environment friendly manner for the
synthesis of title compounds. In this context, we, herein,
report an ultrasound-assisted20 convenient method for the
preparation of methoxylated (E)-arylalkenes (3a–3g) and
arylalkanones (3h–3j) via DDQ-assisted oxidation of
arylalkanes (2a–2j) obtained by hydrogenation of isomeric
mixture of arylalkenes (1a–1j) (Scheme 1).
Hypercholesterolemia1 appears to be a serious risk factor for
coronary heart diseases (CHDs). High level of low-density
lipoprotein (LDL) are recognized as the initiating event in
CHDs. LDL can undergo extensive lipid peroxidation,
resulting in the generation of modified LDL and the
formation of atheromatic lesions. Hence, implementation
of hypolipidemic drugs in any heart disease prevention
therapy is an imperative strategy. In this regards, various
hypolipidemic drugs2 such as statins, clofibrate, niacins etc.
are found effective. On the other side, a large number of
plant extracts3 as well as natural molecules4 including
phenylpropanoids5 and phenylbutanoids5b,6 have also
shown promising results. Among them, some methoxylated
phenylpropanoids and phenylbutanoids like (E)-aryl-
alkenes7 (such as a-asarone) (3a–3g) and arylalkanones7,8
(such as isoacoramone) (3h–3j) are reported to be active
hypolipidemic agents. Besides possessing hypolipidemic
activities, these natural compounds (3a–3j) are known to
have a wide range of biological9 activities such as
neuroleptic, anti-ulcerogenic, anti-atherogenic, anti-
inflammatory, anti-choleretic, anti-PAF, anti-fungal and
anti-platelet activities. Various synthetic methods are
reported for (E)-arylalkenes which involve Grignard,10
Wittig–Horner,11 Aldol–Grob,12 Wittig,6 Friedel–Crafts7
and photochemical isomerization13 reactions. However, all
2. Results and discussion
* IHBT communication No. 0361.
As per our continuing efforts towards chemical
modification of abundantly15 available toxic14 (Z)-1-
(20,40,50-trimethoxyphenyl)prop-1-ene (commonly known
as b-asarone) (1a) into value0 added products,21 synthesis of
hypolipidemic (E)-1-(20,40,5 -trimethoxyphenyl)prop-1-ene
Keywords: Hypolipidemic; Ultrasound; (E)-Arylalkenes; Arylalkanones;
DDQ.
* Corresponding author. Tel.: C91 1894 230426; fax: C91 1894 230433;
e-mail: aksinha08@rediffmail.com
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.071

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B. P. Joshi et al. / Tetrahedron 61 (2005) 3075–3080
Scheme 1.
a-asarone) (3a) was undertaken from 1a as a starting
compound. Treatment of 1a, containing an isomeric
mixture of a- and/or g-asarone (3-(20,40,50-trimethoxy-
phenyl)prop-1-ene), with ammonium formate22 and Pd/C
provided 1-(20,40,50-trimethoxyphenyl)propane23 (dihydro-
asarone) (2a) in quantitative yield in 30 min while
conventional method required 10–12 h for complete hydro-
genation of 1a into 2a. In the next step, dehydrogenation of
2a into 3a was attempted with various dehydrogenating
reagents24 such as Pd–C in diphenylether, SeO2 and
chloranil but none were successful. In all the above
conditions, the reaction did not go to completion, and
mostly the starting 2a remained unreacted. Later on, the
attention was shifted to the use of 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ)25 and reaction of 2a with 1.0–
1.1 M equiv of DDQ in dry toluene under nitrogen
atmosphere, furnished the corresponding dehydrogenated
product 3a in 32% yield with a large amount of unreacted
starting compound 2a. Use of 1.25 M equiv of DDQ in
toluene provided 3a in 45% yield and it did not improve
further, even when using excess of DDQ and refluxing the
mixture for 20 h. Similarly, the above reaction was carried
out in MeOH which afforded 23% of the product 3a and rest
of the starting 2a remained unreacted. However, in 1,4-
dioxane as solvent, reaction of 2a with 1.25 equiv DDQ
increased the yield of 3a up to 52% along with a yellow
coloured side product, that is, (E)-3-(20,40,50-trimethoxy-
phenyl)prop-2-en-1-al26 (4a, 12% yield). There was no
further improvement in the yield of 3a with increasing the
amount of DDQ. The spectroscopic analysis and compari-
son with the reported7,26 data clearly indicated both 3a and
4a exclusively with trans selectivity. Interestingly, when a
catalytic amount of pre-activated silica gel was added to the
above reaction mixture, the yield of 3a increased up to 72%
with 18% yield of 4a at room temperature under nitrogen
atmosphere. This incremental effect due to silica gel was
presumed to be due to its mild acidic nature which, in
catalytic amounts, would initiate the protonation of DDQ
and facilitate the reaction (Table 1). In order to increase the
yield of 3a further, we performed the same dehydrogenation
reaction of 2a under sonication20 for 40 min. However,
instead of increasing yield of 3a, it increased the yield of 4a
up to 29% at the cost of desired 3a which got reduced to
48%. Increase in the yield of 4a could be due to the presence
of atmospheric oxygen/moisture in the reaction mixture
during sonication, which would form highly reactive peroxy
radicals27 to further oxidize 3a into 4a. It is evident from the
fact that maintenance of nitrogen atmosphere during
conventional method limits the yield of 4a to 18% only.
Having been successful with the synthesis of 3a, the
combination of DDQ–silica-dioxane successfully converted
2b–2g, dihydro products23 of 1b–1g, into 3b–3g with a little
amount of corresponding (E)-arylalkenals26 (4b–4e) and no
arylalkenals were detected in case of 2f–2g (Table 2). After
successful synthesis of a series of hypolipidemic (E)-
arylalkenes (3a–3g), we shifted our focus towards synthesis
of hypolipidemic arylalkanones 3h–3j. In the same method
of treatment of 2a with DDQ–silica-dioxane, a few drops of
water were added which provided 3h in 43% yield with
mere 7% of 3a, without formation of any 4a, within 10 h.
Reaction conditions were optimized and 2.2 equiv of
Table 1. Oxidation of arylalkane (2a) into (E)-arylalkene (3a) with varying amounts of DDQ in different solvents
Entry
DDQ (in M equiv)
Solvents
Yield of 3a (%)
1
2
3
4
5
6
7
1.0–1.1
1.25
1.50
1.25
Toluene
Toluene
Toluene
MeOH
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
32
45
43
23
52
72
48
1.25
1.25Csilica gel (cat.)
1.25Csilica gel (cat.) (under sonication)

B. P. Joshi et al. / Tetrahedron 61 (2005) 3075–3080
3077
Table 2. DDQ assisted oxidation of arylalkanes (2) into (E)-arylalkenes/arylalkanones (3) and (E)-arylalkenal (4)
Entry
Arylalkane (2)
Methoda
E-Arylalkene/arylalkanone (3)
E-Arylalkenal (4)
72%
18%
a
A
70%
63%
14%
b
c
d
A
A
A
11%
56%
12%
42%
7%
e
f
A
A
54%
49%
—
—
—
g
h
A
B
64%
65%
i
B
—
59%
j
B
—
—
k
A or B
—
a Method A: DDQ (1.25 equiv)/dry dioxane/silica gel; Method B: DDQ (2.2 equiv)/wet dioxane/silica gel.
DDQ25 was found most suitable with 2a and silica-dioxane-
water to provide maximum yield of 3h up to 57% within
10 h, whereas the same reaction provided 64% of 3h in
20 min under sonication. No more increase in the yield of 3h
was observed by increasing either the sonication period or
the heating temperature of the reaction mixture. Similarly,
3i–3j got formed in 65 and 59%, yield respectively under
sonication during oxidation of 2i–2j. It was interesting that,
oxidation of 2k did not provide corresponding (E)-alkene or
alkanone (3k) with either DDQ–silica-dioxane or DDQ–
silica-dioxane-water-sonication, and mostly the starting
material was recovered. This indicates that the presence of

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B. P. Joshi et al. / Tetrahedron 61 (2005) 3075–3080
methoxy group in the aryl ring plays an important role in the
oxidation of 2a–2j (Table 2). However, further studies
regarding this mechanistic aspect influenced by the
structural variation of the starting compounds is under
progress. It is worth mentioning that the use of DDQ has so
far been reported in the formation of arylpropenals26 from
arylpropenes, but removal of double bond of arylpropenes
by conversion into arylpropanes followed by oxidation
with DDQ is a new method for the formation of various
bioactive compounds, including hypolipidemic (E)-aryl-
alkenes (3a–3g) and arylalkanones (3h–3j).
(0.2–0.3 g, kept at 110–120 8C for 3–4 h before use) in
anhydrous dioxane (30 mL) was stirred at room temperature
for 12–14 h under nitrogen atmosphere till completion of
the reaction. The precipitated DDQH2 was filtered and the
filtrate was evaporated and subsequently chromatographed
on silica gel (hexane:ethyl acetateT7:3) to provide 3a–3g
in 42–72% yield along with some amount of (E)-
arylalkenal (4a–4e) (Table 2). The spectral data of
compounds (3a–3g and 4a–4e) agreed well with the
reported values.7,8,10,17c,18,21,23,28
4.3.1. 1-(20,40,50-Trimethoxyphenyl)prop-1-ene (3a).7b
Yield 72%; white solid; mp 44–45 8C (lit.7b mp 44–
1
45 8C); H NMR (CDCl3): d 6.91 (1H, s, H-60), 6.64 (1H,
3. Conclusion
dq, JZ16.0, 1.5 Hz, H-1), 6.45 (1H, s, H-30), 6.02 (1H, dq,
JZ16.0, 6.2 Hz, H-2), 3.84, 3.81 and 3.77 (each 3H, s, three
OCH3),1.87 (3H, dd, JZ6.2, 1.5 Hz, H-3).
In conclusion, we have realized an ultrasound-assisted
convenient semi-synthetic approach towards preparation of
a number of natural hypolipidemic compounds (3a–3j) from
commercially available isomeric mixture of substituted
arylalkenes (1a–1j) via intermediate arylalkanes (2a–2j).
Moreover, our studies strongly emphasize the change in the
products from arylalkenes (3a–3g) on one side to aryl-
alkanones (3h–3j) on the other, with a little change in the
ratio of DDQ and the reaction conditions from anhydrous to
aqueous medium.
4.3.2. 1-(30,40,50-Trimethoxyphenyl)prop-1-ene (3b).7b
Yield 70%; liquid; 1H NMR (CDCl3): d 6.50 (2H, s,
H-20 and H-60), 6.31 (1H, dq, JZ15.7, 1.4 Hz, H-1),
6.12 (1H, dq, JZ15.7, 6.3 Hz, H-2), 3.81 (3H, s, OCH3),
3.78 (6H, s, two OCH3), 1.82 (3H, dd, JZ6.3, 1.4 Hz,
H-3).
4.3.3. 1-(30,40-Dimethoxyphenyl)prop-1-ene (3c).17c Yield
1
63%; liquid; H NMR (CDCl3): d 6.90–6.78 (3H, m, H-20,
4. Experimental
H-50 and H-60), 6.35 (1H, d, JZ16.2 Hz, H-1), 6.22–6.11
(1H, m, H-2), 3.87 and 3.83 (each 3H, s, two OCH3), 1.87
(3H, d, JZ6.2 Hz, H-3).
4.1. General methods
Melting points were determined with a Mettler FP80
micromelting point apparatus and are uncorrected. Column
chromatography was performed on silica gel (60–120 mesh
4.3.4. 1-(30,40-Dioxymethylenephenyl)prop-1-ene (3d).8
1
Yield 56%; Liquid; H NMR (CDCl3): d 6.92–6.77 (3H,
m, H-20, H-50 and H-60), 6.35 (1H, d, JZ16.2 Hz, H-1),
6.25–6.11 (1H, m, H-2), 5.95 (2H, s, –OCH2O–), 1.95 (3H,
d, JZ6.2 Hz, H-3).
1
size). H (300 MHz) NMR spectra was recorded in CDCl3
on a Bruker Avance-300 spectrometer. Sonication (20 kHz,
400 W; Pulse length:10 s; 75% duty) was used for all the
given reactions.
4.3.5. 1-(40-Methoxyphenyl)prop-1-ene (3e).17c Yield
1
42%; liquid; H NMR (CDCl3): d 7.07–6.96 (2H, m, H-20
4.2. General procedure for ultrasound-assisted
conversion of toxic methoxylated cis-arylalkenes
containing an isomeric mixture of trans and gamma-
isomers (1a–1k) into arylalkanes (2a–2k)
and H-60), 6.88–6.80 (2H, m, H-30 and H-50), 6.39 (1H, d,
JZ16.2 Hz, H-1), 6.18–6.11 (1H, m, H-2), 3.83 (3H, s,
OCH3), 1.87 (3H, d, JZ6.2 Hz, H-3).
4.3.6. 1-(20,40,50-Trimethoxyphenyl)-1-butene (3f).6a
Yield 54%; mp 40–41 8C (reported as a pale yellow liquid
in literature6a); 1H NMR (CDCl3): d 6.82 (1H, s, H-60), 6.54
(1H, d, JZ16.2 Hz, H-1), 6.29 (1H, s, H-30), 5.96 (1H, m,
H-2), 3.66 (6H, s, two OCH3), 3.60 (3H, s, OCH3), 2.08 (2H,
m, H-3), 0.93 (3H, t, JZ7.1 Hz, H-4).
The isomeric mixture of methoxylated arylalkenes 1a–1k
(0.044 mol), 10% Pd/C (0.75–1.20 g) and ammonium
formate (0.41 mol) in ethanol (200 mL) was sonicated for
30–40 min. After completion of the reaction, the catalyst
was removed by filtration and the filtrate was evaporated.
The residue was partitioned between ethyl acetate (70 mL)
and water (15 mL) and the ethyl acetate layer was washed
with water (2!10 mL), 10% HCl (2!5 mL), brine (2!
10 mL), dried over Na2SO4 and filtered. The filtrate was
evaporated and the obtained residue was purified by column
chromatography (silica gel, hexane:ethyl acetateT9:1) to
afford arylalkane 2a–2k in quantitative yield whose spectra
were found matching with the reported values.23
4.3.7. 1-(30,40-Dimethoxyphenyl)-1-butene (3g).6a Yield
1
49%; liquid; H NMR (CDCl3): 6.90–6.79 (3H, m, H-20,
H-50 and H-60), 6.51 (1H, d, JZ16.1 Hz, H-1), 5.42 (1H, m,
H-2), 3.84 and 3.81 (each 3H, s, two OCH3), 2.21 (2H, m,
H-3), 1.02 (3H, t, JZ7.0 Hz, H-4).
4.3.8.
3-(20,40,50-Trimethoxyphenyl)prop-2-en-1-al
4.3. General procedure for dehydrogenation of
methoxylated arylalkanes (2a–2g) into (E)-arylalkenes
(3a–3g)
(4a).26 Yield 18%; yellow solid; mp 139–140 8C (lit.26
140–142 8C); H NMR (300 MHz, CDCl3): d 9.65 (1H, d,
1
JZ7.8 Hz, H-1), 7.81 (1H, d, JZ15.8 Hz, H-3), 7.03 (1H, s,
H-600), 6.64 (1H, dd, JZ15.8, 7.8 Hz, H-2), 6.51 (1H, s,
H-3 ), 3.95, 3.91 and 3.87 (each 3H, s, three OCH3).
Arylalkane 2a–2g (2.4 mmol), DDQ (3.0 mmol), silica gel

B. P. Joshi et al. / Tetrahedron 61 (2005) 3075–3080
3079
4.3.9. 3-(30,40,50-Trimethoxyphenyl)-prop-2-en-1-al
Acknowledgements
(4b).26 Yield 14%; yellow solid; mp 110 8C (lit.26 109–
111 8C); 1H NMR (CDCl3): d 9.68 (1H, d, JZ7.8 Hz, H-1),
7.58 (1H, d, JZ15.8 Hz, H-3), 6.630 (1H, dd, JZ15.8,
7.8 Hz, H-2), 6.26 (2H, s, H-20 and H-6 ), 3.73 (9H, s, three
OCH3).
Two of us (BPJ and AS) are indebted to CSIR, Delhi for the
award of SRF. The authors gratefully acknowledge the
Director of I.H.B.T., Palampur for his kind cooperation and
encouragement.
4.3.10. 3-(30,40-Dimethoxyphenyl)prop-2-en-1-al (4c).
Yield 11%; mp 78 8C (lit.28 mp 78–79 8C); 1H NMR
(CDCl3): d 9.67 (1H, d, JZ7.8 Hz, H-1), 7.43 (1H, d, JZ
15.8 Hz, H-3), 7.15 (1H, d, JZ8.1 Hz, H-60), 7.08 (1H, s,
H-20), 6.91 (1H, d, JZ8.1 Hz, H-50), 6.61 (1H, dd, JZ15.8,
7.8 Hz, H-2), 3.94 and 3.93 (each 3H, s, two OCH3).
References and notes
1. (a) Neil, H. A.; Mant, D.; Jones, L.; Morgan, B.; Mann, J. I. Br.
Med. J. 1990, 301, 584. (b) McCully, K. S. Nat. Med. 1996, 2,
386. (c) Chrysselis, M. C.; Rekka, E. A.; Kourounakis, P. N.
J. Med. Chem. 2000, 43, 609.
4.3.11. 3-(30,40-Dioxymethylenephenyl)prop-2-en-1-al
1
(4d). Yield 12%; mp 78 8C (lit.28 mp 77 8C); H NMR
2. (a) Mantell, G.; Burke, M. T.; Staggers, J. Am. J. Cardiol.
1990, 66, B11. (b) Ceska, R.; Melenovsky, V.; Malik, J.;
Kralikova, E.; Stulc, T.; Vrablik, M. Int. Congress Ser. 2004,
1262, 458.
(CDCl3): d 9.88 (1H, d, JZ7.8 Hz, H-1), 7.38 (1H, d, JZ
15.8 Hz, H-3), 6.75 (1H, d, JZ8.2 Hz, H-60), 6.70 (1H, s,
H-20), 6.63 (1H, d, JZ8.2 Hz, H-50), 6.56 (1H, dd, JZ15.8,
7.8 Hz, H-2), 6.10 (2H, s, –OCH2O–).
3. (a) Chen, C. C.; Hsu, J. D.; Wang, S. F.; Chiang, H. C.; Yang,
M. Y.; Kao, E. S.; Ho, Y. C.; Wang, C. J. J. Agric. Food Chem.
2003, 51, 5472. (b) Allen, K. G. D.; Bristow, S. J.; Yu, L.
J. Agric. Food Chem. 2004, 52, 4998.
4.3.12. 3-(40-Methoxyphenyl)prop-2-en-1-al (4e).28 Yield
1
7%; white solid, mp 58–59 8C (lit.28 mp 59 8C); H NMR
(CDCl3): d 9.68 (1H, d, JZ7.8 Hz, H-1), 7.58 (1H, d, JZ
15.8 Hz, H-3), 7.19 (2H, m, H-20 and H-60), 6.72 (2H, m,
H-30 and H-50), 6.63 (1H, dd, JZ15.8, 7.8 Hz, H-2), 3.73
(3H, s, OCH3).
´
4. (a) Ramırez-Tortosa, M. C.; Mesa, M. D.; Aguilera, M. C.;
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Quiles, J. L.; Baro, L.; Ramırez-Tortosa, C. L.; Martinez-
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Mol. Aspects Med. 2003, 24, 391. (d) Vastano, B. C.; Chen, Y.;
Zhu, N.; Ho, C. T.; Zhou, Z.; Rosen, R. T. J. Agric. Food.
Chem. 2000, 48, 253.
4.4. General procedure for ultrasound-assisted synthesis
of methoxylated arylalkanones (3h–3j) from oxidation of
arylalkanes (2a–2b and 2f) with DDQ
´
´
5. (a) Enqiquez, R. G.; Chavez, M. A.; Jauregui, F. Phyto-
chemistry 1980, 19, 2024. (b) Harborne, J. B.; Baxter, H.
Phytochemical Dictionary: A Handbook of Bioactive Com-
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Malgorzata, S.; Zdzislaw, C. J. Med. Chem. 2000, 43, 3671.
A mixture of substituted arylalkane (2a–2b and 2f)
(2.4 mmol), DDQ (4.8–5.24 mmol), 10% HCl (1–2 drops)
in wet dioxane (30 mL, dioxane:waterT90:10) was stirred
under sonication for 20 min. The precipitated DDQH2 was
filtered and the red coloured filtrate was evaporated and
subsequently chromatographed on silica gel (hexane:ethyl
acetate 7:3) to provide 3h–3j in 59–65% yield (Table 2).
The spectral data of compounds (3h–3j) agreed well with
the reported values.7,8,21
4.4.1. 1-(20,40,50-Trimethoxyphenyl)-1-propanone (also
known as isoacoramone) (3h).7 Yield 64%; White solid;
mp 108–109 8C (lit.7 mp 109 8C); 1H NMR (CDCl3) d 7.45
(1H, s, H-60), 6.77 (1H, s, H-30), 3.96, 3.93 and 3.89 (each
3H, s, three –OCH3), 2.99 (2H, q, JZ6.9 Hz, H-2), 1.18
(3H, t, JZ6.9 Hz, H-3).
ˇ ´
(c) Cruz, A.; Garduno, L.; Salazar, M.; Martınez, E.; Diaz, F.;
Chamorro, G.; Tamariz, J. Med. Chem. Res. 2001, 10, 587.
´
´
Vazquez, H. A.; Diaz, F.; Chamorro, G.; Tamariz, J. Arzneim.
ˇ ´
8. (a) Cruz, A.; Garduno, L.; Salazar, M.; Martınez, E.; Jimenez-
Forsch. Drug Res. 2001, 51, 535. (b) Chilmonczyk, Z.; Siluk,
D.; Kaliszan, R.; Łozowicka, B.; Popławski, J.; Filipek, S.
Pure Appl. Chem. 2001, 73, 1445.
4.4.2. 1-(30,40,50-Trimethoxyphenyl)-1-propanone (3i).7
1
Yield 65%; White solid; mp 52–53 8C (lit.7 mp 53 8C); H
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4.4.3. 1-(20,40,50-Trimethoxyphenyl)-1-butanone (3j).
Yield 59%; White solid; mp 75–76 8C (lit.7 mp 75–77 8C);
1H NMR (CDCl3) d 7.34 (1H, s, H-60), 6.41 (1H, s, H-30),
3.85, 3.82 and 3.78 (each 3H, s, three –OCH3), 2.87 (2H, t,
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