An efficient 1,3-allylic carbonyl transposition of chalcones

Article abstract of DOI:10.1007/s00706-008-0019-0

A very simple, convenient, and efficient procedure is reported for the 1,3-allylic carbonyl transposition of chalcones. The transposition can be achieved by reduction of chalcones to 1,3-diarylpropan-1-ols and dehydration of the latter to give 1,3-diarylpropenes followed by benzylic/allylic oxidation.

Full text of DOI:10.1007/s00706-008-0019-0

Monatsh Chem (2009) 140:69–72
DOI 10.1007/s00706-008-0019-0
ORIGINAL PAPER
An efficient 1,3-allylic carbonyl transposition of chalcones
Jitender M. Khurana Æ Kiran Dawra Æ
Susruta Majumdar
Received: 8 December 2007 / Accepted: 2 June 2008 / Published online: 22 August 2008
Ó Springer-Verlag 2008
Abstract A very simple, convenient, and efficient pro-
cedure is reported for the 1,3-allylic carbonyl transposition
of chalcones. The transposition can be achieved by
reduction of chalcones to 1,3-diarylpropan-1-ols and
dehydration of the latter to give 1,3-diarylpropenes fol-
lowed by benzylic/allylic oxidation.
have anticancer and antibacterial activity [7–9]. Hence,
there is a need for synthesis of new chalcones, which may
be difficult to prepare by conventional methods owing to
the non-availability of appropriate starting materials.
Results and discussions
Keywords Dehydration ꢀ 1,3-Diarylpropenes ꢀ
Oxidation ꢀ Tetrahydrochalcones ꢀ Transposed chalcones
We now report a new synthesis protocol wherein one
chalcone can be converted to another by 1,3-allylic trans-
position of the carbonyl group. The transposition can be
achieved by (1) reduction of chalcones to 1,3-diarylpropan-
1-ols, (2) dehydration of 1,3-diarylpropan-1-ols to 1,3-di-
arylpropenes, and (3) oxidation of 1,3-diarylpropenes
without rearrangement. Recently, we have reported that
chalcones 1 can be rapidly reduced to the corresponding
1,3-diarylpropan-1-ols 2 with nickel boride, generated in
situ from anhydrous nickel chloride and sodium borohy-
dride in methanol at ambient temperature [10]. With these
results in hand, we attempted dehydration of 1-phenyl-3-
(4-tolyl)propan-1-ol (2a) with a variety of reagents known
for dehydration of alcohols [11]. Dehydration with cata-
lytic amounts of p-toluene sulphonic acid (PTSA) in
benzene using Dean-Stark apparatus, under reflux,
appeared to be the ideal procedure for these substrates.
Reaction was completed in 45 min, as monitored by TLC,
giving 1-phenyl-3-(4-tolyl)propene (3a) in 95% yield. All
other 1,3-diarylpropan-1-ols (2b–2f) also underwent
dehydration smoothly under these conditions, giving
corresponding 1,3-diarylpropenes (3b–3f) (Scheme 1,
Table 1). All the 1,3-diarylpropenes are known, and they
were identified by comparison of spectral data with [12, 13].
Allylic oxidation of 1,3-diarylpropenes posed some
problems. Oxidation of 3a was attempted with CrO3/
AcOH/H2O, NBS/DMSO, NBS/THF/H2O, DDQ/dioxane,
Introduction
Efficient transposition of a functional group from one
carbon to another, as in 1,3-carbonyl transposition of a,b-
unsaturated ketones, offers a wide degree of flexibility in
synthesis design of many naturally occurring compounds
[1, 2]. A number of synthesis methods and reagents are
available for effecting allylic carbonyl transposition. In
general, however, these methods suffer from low yields
and/or multi-step manipulation of delicate intermediates
and alkylation of intermediates [2]. The reported transpo-
sition of chalcones is noteworthy, not only from the
viewpoint of the novelty in the reaction path, but also in
view of the importance of the products (chalcones), which
serve as starting materials for the synthesis of flavan-4-ols,
flavanones, 3-hydroxy flavones, heterocyclic compounds,
etc. [3, 4]. Chalcones are also known to possess multi-
pronged activity, e.g. as antihypertensives, cardiovascular
agents, bronchodilators, and immunomodulators [5, 6], and
J. M. Khurana (&) ꢀ K. Dawra ꢀ S. Majumdar
Department of Chemistry, University of Delhi,
Delhi 110007, India
e-mail: jmkhurana@du.ac.in
123

70
J. M. Khurana et al.
Scheme 1
OH
PTSA in benzene
Dean-Stark apparatus
R'
R
R
R'
2a-2g
3a-3g
Table 1 Dehydration of 2 to 3 and oxidation of the latter to transposed product 4
S.No.
3 Yield/%
(2 to 3)
4 Yield/%
(3 to 4)
2
3
4
O
OH
OH
Ph
Ph
Ph
Ph
Ph
a
95
83
50
58
H3C
H3C
H3C
O
Ph
b
H3CO
H3CO
H3CO
OH
O
Ph
Ph
Ph
Ph
c
84
79
53
51
Br
Cl
Br
Cl
Br
Cl
OH
O
Ph
Ph
d
HO
O
Ph
Ph
Ph
Ph
89
87
58
54
e
f
Br
Br
Cl
Br
OH
O
Ph
Ph
Cl
Cl
DDQ/dioxane/pyridine and DDQ/CHCl3/H2O, but in none
of these cases was the desired product obtained. The
reaction of 3a with DDQ in CHCl3/H2O/reflux was slug-
gish, and none of the products corresponded to the desired
one. When 3a was heated under reflux with 3 equiv. of
DDQ in CH3COOH, the reaction was complete in 3 h. but
the product obtained was the completely rearranged prod-
uct, 1a (starting chalcone), and not the desired product, 4a.
Similarly, reaction of 3b also gave the rearranged product,
1b, under these conditions, implying that oxidation of
allylic/benzylic –CH2– was proceeding along with the
rearrangement. The reaction of 3a with DDQ (2 equiv.) in
123

1,3-Allylic carbonyl transposition of chalcones
71
Scheme 2
O
SeO2, ethanol
reflux, 24 h
R'
R
R'
R
4a-4g
3a-3g
Scheme 3
OH
PTSA, benzene, reflux
R
R'
R
R'
Dean-Stark apparatus
79-95%
2a-2f
3a-3f
NiCl2, NaBH4
dry MeOH, r.t.
SeO2, ethanol
reflux, 24 h
O
O
R
R'
R
R'
1a-1f
4a-4f
CH2Cl2/H2O (4:1) at room temperature yielded a nearly 1:1
mixture of 4a and 1a, but it proved impossible for us to
separate the two chalcones. Neither increasing the amount
of water from 5% to 50% nor higher molar ratios of sub-
strate to DDQ changed the reaction rate appreciably and
increased the concentration of 4a noticeably. Other sol-
vents such as methanol and methanol–water were also of
no help.
FT-NMR model R-300 Hitachi (300 MHz) with TMS as
the internal standard. All the products were well known and
were identified by co-TLC, m.p., mixed m.p. (wherever
applicable), IR, NMR, and mass spectra with the authentic
sample. Literature melting points are cited from [15–18].
General procedure for the reduction of chalcones 1
with nickel boride
Selenium dioxide proved to be the most reliable reagent
for the direct insertion of oxygen at the allylic carbon
regioselectively to give the desired products. We attempted
reactions of 3a by changing molar ratios of substrate to
SeO2 and solvents to achieve the desired transformation.
The reaction of 3a with SeO2 in ethanol gave p0-methyl
chalcone 4a in 50% yield. Other 1,3-diarylpropenes 3b–3f
were oxidized under identical conditions to transposed
chalcones (Scheme 2, Table 1). All the products are
known, and they were identified by comparison of their
spectral data with those in [14–18].
In a typical experiment, 1.0 g p-methyl chalcone (1a)
(4.50 mmol), 1.16 g anhydrous nickel chloride (9.0 mmol),
and 25 cm3 dry methanol were stirred magnetically under
a nitrogen atmosphere. Sodium borohydride (1.02 g,
27.02 mmol) was added to the mixture carefully, and the
contents were stirred vigorously. TLC analyses (petroleum
ether:ethyl acetate 95:5, v/v) showed complete reduction
after 5 min. The reaction mixture was filtered through a
celite pad (*2.5 cm). The filtrate was diluted with
ca. 50 cm3 water. It was extracted with 3 9 10 cm3 CH2Cl2,
washed with ca. 10 cm3 water, dried over anhydrous sodium
sulfate, and concentrated in a Bu¨chi rotary evaporator. The
crude product was purified by column chromatography on
neutral alumina (petroleum ether:ethyl acetate 92:8, v/v).
1-Phenyl-3-(4-tolyl)propan-1-ol (0.814 g, 80%) (2a) was
obtained as a white solid, m.p. 54–56° C ([16] 56 °C).
In conclusion, the successful 1,3-allylic carbonyl trans-
position of chalcones had been achieved in moderate-to-
good yields. The reaction sequence and conditions repre-
sent significant improvement over existing methodologies
(Scheme 3).
Experimental
General procedure of dehydration of 1,3-diarylpropan-
1-ols 2 with PTSA
All the melting points were recorded on Tropical Labequip
apparatus. IR spectra were recorded on Perkin-Elmer FT-
IR SPECTRUM-2000. NMR spectra were recorded on an
In a typical reaction, a solution of 0.5 g 1-phenyl-3-(4-
tolyl)propan-1-ol (2a) (2.40 mmol) in 50 cm3 of benzene
123

72
J. M. Khurana et al.
Acknowledgments Financial assistance by UGC, New Delhi, F. no.
32-203/2006(SR), and SRF to K. Dawra by CSIR, New Delhi, India,
is gratefully acknowledged.
and a catalytic amount of PTSA (0.01 g) was refluxed for
45 min in a 100-ml round-bottomed flask fitted with a
Dean-Stark apparatus. The progress of the reaction was
monitored by TLC (petroleum ether:ethyl acetate 95:5,
v/v). The reaction mixture was cooled and neutralized with
25 cm3 of saturated NaHCO3 solution. The benzene layer
was separated and dried over anhydrous sodium sulfate.
The solvent was removed in a rotary evaporator, and the
product was purified by column chromatography using
neutral alumina and petroleum ether, to yield 1-phenyl-3-
(4-tolyl)propene (3a) (0.437 g, 95%) as a colourless oil
identical to the product described in [12].
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