Convenient syntheses of 3-aryl-3,4-dihydroisocoumarins

Article abstract of DOI:10.3184/174751915X14258938697567

A convenient method for the synthesis of naturally occurring 3,4-dihydroisocoumarins by judicious use of Friedel-Craft acylation, regioselective formylation and oxidative cyclisation reactions is described. O-methylated analogues of montroumarin and thunb

Full text of DOI:10.3184/174751915X14258938697567

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 APRIL, 191–194
RESEARCH PAPER 191
Convenient syntheses of 3‑aryl‑3,4‑dihydroisocoumarins
Rohan A. Limaye, Augustine R. Joseph, Arun D. Natu* and Madhusudan V. Paradkar
Post Graduate and Research Centre, Department of Chemistry, MES Abasaheb Garware College, Karve Road, Pune 411004, India
A convenient method for the synthesis of naturally occurring 3,4-dihydroisocoumarins by judicious use of Friedel–Craft acylation,
regioselective formylation and oxidative cyclisation reactions is described. O-methylated analogues of montroumarin and thunberginols
C and D and have been synthesised using 3,5-dimethoxyphenylacetic acid as a starting material. Furthermore, the starting material
3,5-dimethoxyphenylacetic acid was synthesised by a route involving an oxidative Nef reaction.
Keywords: montroumarin, thunberginol C, thunberginol D, Friedel–Craft acylation, Nef reaction
3,4‑Dihydroisocoumarins 1 constitute one of an important
class of naturally occurring bioactive oxygen heterocycles that
are often found together with corresponding isocoumarins
in fungi, plants, and insects.1–4 These are important
secondary metabolites and have been shown to be involved
in the biosynthetic pathways of several other metabolites.2
Structurally, they possess 3,4‑dihydroisochromen‑1‑one as
a basic structural unit that carries substitutions on either or
both the rings. These substitutions influence their biological
activity (see ref. 4 and references therein). It was evident from
the literature that most biologically active dihydroisocoumarins
possess substituents at the C‑3 position on the lactone ring.4 One
of the significant class of C‑3 substituted dihydroisocoumarins
comprises the 3‑aryl‑3,4‑dihydroisocoumarins. Members of
this class differ from each other by number and type of oxy‑
substituents on the aromatic rings. They also exhibit a wide
range of pharmacological activities such as antifungal, antiulcer,
antileukaemic, antiallergic, and antimalarial activities.5–16
This fascinating class of natural products had generated
much attention from synthetic chemists owing to their
occurring and potentially antiallergic and antimicrobial agents
of this family montroumarin 2 and thunberginols C 3 and D 4
that have been isolated from various Japanese traditional plants
Montrouziera sphaeroidea,16 Hydrangea macrophylla16 and
Thunbergii MAKINO6–9 species, respectively.
Retrosynthetic analysis of the target molecules revealed that
these molecules can be obtained through a synthetic route based
on Friedel–Craft acylation (FCA) as a key step. We therefore
designed the synthetic strategy shown in Scheme 1 starting
from 3,5‑dimethoxyphenylacetic acid 5 giving emphasis to
easily accessible reagents and simple reaction conditions.
To achieve the synthesis of the target molecules through
FCA, we required 3,5‑dimethoxyphenylacetic acid 5. With
our earlier success28 in developing alternative synthetic
route for aryl acetic acid using Nef reaction,29 we decided
to obtain the desired acid 5 by devising a similar synthetic
route involving the oxidation of an aryl nitroalkane, prepared
from commercially available 3,5‑dimethoxybenzaldehyde as
depicted in Scheme 2.
The 3,5‑dimethoxybenzaldehyde 6 was first subjected
to condensation with nitromethane in presence of
ammonium acetate–acetic acid to provide the corresponding
1,3‑dimethoxy‑5‑{(E)‑2‑nitrovinyl}benzene 7 in 90% yield.
Selective reduction of 7 to 2‑(3,5‑dimethoxyphenyl)nitroethane
8 was achieved using a sodium borohydride in ethyl acetate‑
ethanol (4:1) combination. The key step was the oxidation
of 8 to (3,5‑dimethoxyphenyl) acetic acid 5. Judicious use of
sodium nitrite in DMSO with a sub‑stoichiometric amount
acetic acid in catalytic quantity28 gave better yield and quality
of the desired 3,5‑dimethoxyphenylacetic acid 5.
Having obtained the starting material, we then focused on the
synthesis of a methyl analogue of montroumarin 21. The first
step in the synthesis of target molecule was the FCA reaction
between 3,5‑dimethoxyphenylacetyl chloride (prepared from
reaction of 3,5‑dimethoxyphenyl acetic acid 5 with thionyl
chloride) and benzene in the presence of AlCl3 at 0 °C. On
completion of this reaction after 1 h (TLC), the reaction was
worked up to provide a dark brown oil (80%), which was
purified by column chromatography over silica gel using
hexane–ethylacetate as eluent to furnish light brown viscous
oil. It was characterised by using spectroscopic techniques
and confirmed as 9 by comparison with literature data.30 The
deoxybenzoin 9 thus obtained was then subjected to reduction
using sodium borohydride in methanol at room temperature.
The reaction was over in 1 h and it was decomposed using ice‑
cold solution of NH4Cl. Usual workup of the resultant mixture
afforded the corresponding alcohol 12 in almost pure form
as pale yellow oil, which was as it is subjected to acylation
reaction using acetic anhydride in presence of pyridine at room
temperature. The crude product thus obtained was purified
further by column chromatography over silica gel (hexane
pharmacological properties and as
a
result, several
methodologies were developed for their synthesis.17–26 It
was observed that these dihydroisocoumarins were mainly
synthesised either by using lithiation17–19 or titanium catalysed
alkyne annulation25 and some ring expansion strategies.26,27
It was therefore, decided to develop a convenient synthetic
methodology towards these types of molecules. As a prototype
for such dihydroisocoumarins, we have selected some naturally
O
OH O
8
1
O
2
7
O
A
5
B
4
3
R
6
HO
3,4-Dihydroisocoumarin
Montroumarin
2
1
OH
O
OH
O
O
O
OH
OH
HO
HO
OH
Thunbeginol C
Thunberginol D
4
3
Fig. 1
Structures of 3,4-dihydroisocoumarins.
* Correspondent. E‑mail: arun.natu@gmail.com

192 JOURNAL OF CHEMICAL RESEARCH 2015
OMe
OMe
OMe
b
a
OH
O
R
R
COOH
MeO
MeO
MeO
R1
R1
5
9: R=R1= H
10: R=H, R1= OMe
11: R=R1=OMe
12: R=R1= H
13: R=H, R1= OMe
14: R=R1=OMe
c
OMe
CHO
OAc
OMe
OAc
OMe O
e
d
O
R
R
R1
R
MeO
MeO
MeO
R1
R1
21: R=R1= H
22: R=H, R1= OMe
23: R=R1=OMe
15: R=R1= H
16: R=H, R1= OMe
17: R=R1=OMe
18: R=R1= H
19: R=H, R1= OMe
20: R=R1=OMe
Scheme 1 Synthesis of O-methylated analogues of montroumarin and thunberginols C and D. Reagents and conditions: a: i, SOCl , reflux, 1 h;
ii, Benzene for 9, anisole for 10, 1,2-dimethoxy benzene for 11, AlCl3, RT, 2 h. b: i, NaBH /MeOH, RT, 1 h. c: Ac2O/Pyridine, RT, 3 h. d2: DMF–POCl3,
0 °C–RT, 3 h. e: i, KMnO4, dioxane–water, 80 °C, 45 min; 4ii, conc. HCl, 80 °C, 30 min.
OMe
OMe
OMe
OMe
c
a
b
COOH
MeO
NO2
MeO
NO2
MeO
MeO
CHO
6
8
7
5
Scheme 2 Synthesis of 3,5-dimethoxyphenyl acetic acid. Reagents and conditions: a, Nitromethane, ammonium acetate–acetic acid, 80 °C, 30 min;
b, NaBH4, ethanol–ethyl acetate, 20 °C–RT, 2 h; c, NaNO2–AcOH, DMSO,35 °C, 2 h.
eluent) to furnish the required acetoxy intermediate 15 as a
pale yellow oil.
aromatic substrates (anisole and 1,2‑dimethoxybenzene) to
provide corresponding deoxybenzoin intermediates 10 and 11
respectively. These deoxybenzoins were then converted into
O‑methylated analogues of thunberginols C 22 and D 23 in four
steps by employing a similar synthetic protocol as in the case
of montroumarin (Scheme 1). All the intermediates and target
molecules were characterised using spectroscopic techniques.
In this way, we have established synthetic route for
O‑methylated analogues of montroumarin and thunberginols
C and D by making judicious use of FCA, Vilsmeier–Haack
formylation and oxidative cyclisation reaction. In the literature,
the methyl analogue of montroumarin has already been converted
into naturally occurring montroumarin. On similar lines, the
methyl analogues of thunberginols should be converted into the
natural thunberginols. Furthermore, 3,5–dimethoxyphenyl acetic
acid was synthesised by an oxidative Nef protocol avoiding use of
harmful toxic cyanide reagents.
The next challenge was to achieve selective formylation of 15
on ring A to provide the desired aldehyde 18. On the basis of
the position of the methoxyl groups on ring A, it was thought
that the electron‑rich benzenoid ring A should react faster
than the unsubstituted ring during the aromatic electrophilic
substitution reaction. With this logic, the compound was
subjected to Vilsmeier–Haack formylation under cold
conditions and as expected, the desired aldehyde 18 was
obtained in 75% yields. The next target was to obtain 21. It was
thought that the oxidation of the formyl group to carboxylic
acid group would lead to cyclisation to provide the lactone ring.
The aldehyde 18 was therefore subjected to oxidation using
KMnO4. The reaction was carried out at 80 °C for 1 h and
the reaction mixture was then acidified and heated further at
80 °C for half an hour. It provided a dark brown sticky mass,
which was purified by column chromatography to obtain a
cream coloured solid that melted at 160 °C. It was further
characterised by using spectroscopic techniques and was
confirmed as 6,8‑dimethylmontroumarin 21 by comparison
with the literature.31 Since 6,8‑dimethylmontroumarin 21 has
already been converted into naturally occurring montroumarin
2 merely by demethylation reaction,31 we can accomplish
formal synthesis of montroumarin 2 by using simple chemical
transformations.
Experimental
All solvents were purified and dried by standard procedures prior to
use and all melting points are uncorrected. TLC was performed on
Merck 60 F254 silica gel plates and visualisation was accomplished
by irradiation under UV or exposure to iodine. Crude products were
purified by column chromatography using 100–200 mesh silica gel.
IR spectra were recorded on PerkinElmer spectrum‑BX FTIR as
1
a thin film or KBr pellet and are expressed in cm–1. H and 13C NMR
spectra were recorded on a Varian Mercury spectrometer at 300 MHz
and 75 MHz respectively using CDCl3 as solvent. Chemical shifts are
expressed in δ ppm with reference to TMS as an internal standard.
Elemental analyses were carried out on a Vario EL III elemental
analyser.
We then generalised this successful synthetic strategy to
achievethesynthesisofO‑methylatedanaloguesofthunberginols
C 22 and D 23. Here, we performed AlCl3‑mediated FCA
reaction between 3,5‑dimethoxyphenyl acetyl chloride and

JOURNAL OF CHEMICAL RESEARCH 2015 193
Synthesis of 1,3-dimethoxy-5-(E)-2-nitrovinylbenzene (7)
mixture of 3,5‑dimethoxybenzaldehyde (2.0 g 12 mmol),
(s, 3H, –OCH3), 4.15 (s, 2H, Ar–CH2–CO–), 6.28–6.45 (m, 3H, ArH),
6.85 (d, J=8 Hz, 1H, ArH), 7.53 (bs, 1H, ArH), 7.63 (d, J=8 Hz, 1H,
ArH). Anal. calcd for C18H20O5: C, 68.34; H, 6.37; found: C, 68.22; H,
6.26%.
A
6
ammonium acetate (3.0 g, 50 mmol) and nitromethane (1.5 mL,
20 mmol) in acetic acid (20 mL) was heated to 80 °C for 30 min and
then cooled to room temperature. Ice (100 g) was added to the mixture
and the yellow precipitate was filtered off. Further purification using
column chromatography over silica gel using hexane as eluent provided
1,3‑dimethoxy‑5‑{(E)‑2‑nitrovinyl}benzene 7 as a bright yellow solid.
Reduction of deoxybenzoins; general procedure
Deoxybenzoins 9–11 (2 mmol) were dissolved in distilled methanol
(75 mL) under stirring. To this solution was added sodium borohydride
(10 mmol) in portions, under stirring. The mixture was stirred further
for 1 h. After completion of the reaction, excess methanol was removed
under reduced pressure and the residue was cooled to 0 °C and
decomposed with cold, saturated NH4Cl solution. It was extracted with
three 20 mL portions of ether. The combined ether extract was washed
with water dried over anhydrous Na2SO4 and concentrated under
reduced pressure to provide the desired alcohols 12–14 as pure pale
yellow oils, which were then subjected to subsequent reaction.
1
Yield 2.3 g (90%); m.p. 78ꢀ°C; IR (KBr): 1521, 1458 cm–1. H NMR δ
ppm 3.82 (s, 6H, OCH3), 6.55 (s, 1H, ArH), 6.65 (s,2H, ArH), 7.56 (d,
J=16 Hz, 1H, =CH–NO2),7.95 (d, J=16 Hz, 1H, Ar–CH=C). Anal.
calcd for C10H11NO4: C, 57.41; H, 5.30; N, 6.70; found: C, 57.34; H,
5.38; N, 6.62%.
Synthesis of 2-(3,5-dimethoxyphenyl) nitroethane (8)
NaBH4 (0.5 g, 14 mmol) was added portion‑wise at 20°C to a solution
of 7 (2.0 g, 10 mmol) in ethyl acetate–ethanol (20 mL, 8:2 mmol).
The contents were then stirred at room temperature for 2 h and the
reaction was monitored by TLC. Usual work up followed by column
chromatographic purification over silica gel provided, 1,3‑dimethoxy‑
5‑(2‑nitroethyl)benzene 8 as a reddish oil. Yield 1.6 g, (80%); IR
(KBr): 1540, 1451 cm–1; 1H NMR δ ppm 3.52 (t, J=7 Hz, 2H, Ar–CH2)
3.96 (s, 6H, OCH3), 4.75 (t, J=7 Hz, 2H, –CH2–NO2), 6.5–6.7 (m, 3H,
ArH). Anal. calcd for C10H13NO4: C, 56.87, H, 6.20, N, 6.63; found: C,
56.78, H, 6.31,N, 6.53%.
Acylation of alcohols; general procedure
The alcohol 12–14 (2 mmol) was added to a solution of dry pyridine
(25 mL) and acetic anhydride (25 mL). The reaction mixture was
kept at room temperature with occasional shaking for 3 h. It was
then decomposed over crushed ice with stirring and extracted with
chloroform. The organic layer was successively washed with water,
dilute HCl, saturated sodium carbonate solution and again with
water. It was dried over anhydrous Na2SO4, filtered, concentrated and
purified by column chromatography on silica gel using hexane as the
eluent to provide the acetoxy intermediates.
Synthesis of 3,5-dimethoxyphenylacetic acid (5)
2-(3,5-Dimethoxyphenyl)-1-phenylethyl acetate (15): Yellowish
Sodium nitrite (6.8 g, 90 mol) and then acetic acid (20 mL, 300 mmol)
1
oil; yield 5.1 g (88%); IR (neat): 1745 cm–1; H NMR δ ppm 2.10 (s,
were added to
a
solution of 1,3‑dimethoxy‑5‑(2‑nitroethyl)
3H, –OCOCH3), 2.95 (dd, J=14 & 6 Hz, 1H, Ar–CH), 3.15 (dd,
J=14 & 8 Hz,1H, Ar–CH), 3.72 (s, 3H, –OCH3), 3.78 (s, 3H, –OCH3),
5.75 (dd, J=8, 6 Hz,1H, –O–CH), 6.24–6.30, m, 3H, ArH), 7.14–7.3
(m, 5H, ArH); 13C NMR δꢀppm 21.7 (CH3), 42.3 (CH2), 55.6 (2CH3),
80.6 (CH), 99.8 (CH), 104.2 (2CH), 121.6 (CH), 127.6 (2CH), 129.2
(2CH), 140.1 (C), 141.6 (C), 161.6 (2C), 168.4 (C=O). Anal. calcd for
C18H20O4: C, 71.98; H, 6.71; found: C, 72.04; H, 6.67%.
2-(3,5-Dimethoxyphenyl)-1-(4-methoxyphenyl)ethyl acetate (16):
Colourless oil; yield 5.0 g (88%); IR (neat):1740 cm–1; 1H NMR δ ppm
2.05 (s, 3H, –COCH3), 2.90 (dd, J=14.6 Hz, 1H, Ar–CH), 3.11 (dd,
J=14.8 Hz, 1H, Ar–CH), 3.69 (s, 6H, –OCH3), 3.73 (s, 3H, –OCH3),
5.70 (dd, J=8.6 Hz, 1H,Ar–CH–O), 6.2–6.3 (m, 3H, ArH), 6.8 (d,
J=8 Hz, 2H, ArH), 7.23(d, J=8 Hz, 2H, ArH); 13C NMR δ ppm 42.1
(CH2), 55.2 (2CH3), 56.1 (CH3), 80.1 (CH), 100.2 (CH), 104.3 (2CH),
112.3 (CH), 114.6 (2CH), 128.2 (2CH), 133.3 (C), 141.1 (C), 159.5 (C),
161.5 (2C), 169.6 (C=O). Anal. calcd for C19H22O5: C, 69.07; H, 6.71;
found: C, 69.18; H, 6.75%.
benzene 8 (10 g, 30 mmol) in DMSO (100 mL). The contents were
stirred at 35 °C for 2 h. After completion of reaction, the reaction
mixture was acidified with 10% aq. HCl and extracted with ether
(20 mL×2). Combined organic layers were further treated with aq.
sodium bicarbonate (10%, 20 mL). The two layers were separated
and aqueous layer was acidified with 1:1 HCl (pH=2) when
2‑(3,5‑dimethoxyphenyl)acetic acid 5 was precipitated as a white
solid. Yield 6.9 g (75%), m.p. 112 °C (lit.32 112 °C); IR(KBr): 3260,
1
1684 cm–1; H NMR δ ppm3.56 (s, 2H, Ar–CH2–COOH),3.82 (s,6H,
OCH3),6.35–6.6 (m, 3H, ArH), 10.6 (bs, 1H, –COOH); Anal. calcd for
C10H12O4: C, 61.22; H, 6.16; found: C, 61.11; H, 6.25%.
Synthesis of deoxybenzoin intermediates; general procedure
Freshly distilled thionyl chloride (5.0 mL, 43 mmol) was added to a
solution of 3,5‑dimethoxyphenylacetic acid 5 (4.9 g, 25 mmol) in dry
dichloromethane (50 mL), and the mixture refluxed on a water bath for
1 h. After removing excess thionyl chloride under reduced pressure,
the residue was then treated with aromatic substrate (in excess). The
solution was then cooled to 0 °C and to this cooled solution, AlCl3
(38 mmol) was added in portions under vigorous stirring. The reaction
was over in 2–3 h as indicated by TLC. The reaction mixture was then
poured onto crushed ice and the layers were separated. The organic
layer was washed successively with diluted HCl, water and sodium
bicarbonate solution. Removal of solvent provided a brown sticky mass
which was purified by column chromatography to furnish the desired
deoxybenzoins.
1-(3,4-Dimethoxyphenyl)-2-(3,5-dimethoxyphenyl)ethylacetate
1
(17): Colourless oil; yield 4.9 g (80%); IR (neat):1740 cm–1; HNMR
δ ppm 2.03 (s, 3H, –COCH3), 2.96 (dd, J=14.6 Hz, 1H, Ar–CH),
3.15 (dd, J=14.8 Hz, 1H, Ar–CH), 3.72 (s, 6H, –OCH3), 3.85 (s,
6H, –OCH3), 5.88 (dd, J=8.6 Hz, 1H, Ar–CH–O), 6.20–6.35(m,
3H, ArH), 6.75–6.95 (m, 3H, ArH); 13C NMR δ ppm 21.4 (CH3), 42.2
(CH2), 55.3 (2CH3), 56.4 (2CH3), 79.8 (CH), 100.8 (CH), 104.3 (2CH),
112.7 (CH), 115.9 (CH), 120.2 (CH), 134.3 (C), 141.1 (C), 148.5 (C),
150.2 (C), 161.3 (2C), 168.8 (C=O). Anal. calcd for C20H24O6: C, 66.65;
H, 6.71; found: C, 66.72; H, 6.78%.
2-(3,5-Dimethoxyphenyl)-1-phenylethanone (9): Light brown oil
1
(lit.30: oil); yield 5.3 g (80%); IR (neat): 1695, 1600 cm–1; H NMR δ
Regioselective formylation of acetoxy intermediates; general
procedure
ppm, 3.74 (s, 6H, –OCH3), 4.20 (s, 2H, Ar–CH2–CO–), 6.4 (s, 3H,
ArH), 7.4–7.5 (m, 3H, ArH), 8.0 (d, J=8 Hz, 2H, ArH). Anal. calcd for
C16H16O3: C, 74.98; H, 6.29; found: C, 74.86; H, 6.38%.
A solution of the acetoxy compound 15–17 (2 mmol) in dry N,N‑
dimethylformamide (0.65 mL, 8.34 mmol) was cooled to 0 °C in an
ice bath. To this ice‑cold mixture, phosphorus oxychloride (0.8 mL,
8.34 mmol) was added dropwise and under stirring over a period of
10 min. The reaction mixture was then removed from ice bath and stirred
at room temperature for 3 h. The resulting dark orange mixture was later
decomposed carefully over ice‑cold saturated solution of sodium acetate,
under stirring. The brown oil thus separated was purified by column
chromatography over silica gel using hexane‑ethyl acetate as eluent to
obtain the desired aldehyde intermediates.
2-(3,5-Dimethoxyphenyl)-1-(4-methoxyphenyl)ethanone
(10):
Pale yellow oil; yield 5.9 g (82%); IR (neat):1690, 1590 cm–1;
1H NMR δ ppm 3.69 (s, 6H, –OCH3), 3.80 (s, 3H, –OCH3), 4.11 (s, 2H,
Ar–CH2–CO), 6.17–6.51(m, 3H, ArH), 6.87 (d, J=9 Hz, 2H, ArH),
6.93 (d, J=9 Hz, 2H, ArH). Anal. calcd for C17H18O4, C, 71.31; H, 6.34;
found: C, 71.22; H, 6.40%.
1-(3,4-Dimethoxyphenyl)-2-(3,5-dimethoxyphenyl)ethanone (11):
Pale yellow oil; yield 6.7 g (84%); IR (neat): 1695 cm–1; 1H NMR δ ppm
3.75 (s, 3H, –OCH3), 3.77 (s, 3H, –OCH3), 3.90 (s, 3H, –OCH3), 3.92

194 JOURNAL OF CHEMICAL RESEARCH 2015
2-(2-Formyl-3,5-dimethoxyphenyl)-1-phenylethyl acetate (18): Pale
yellow oil; yield 0.5 g (75%); IR (neat): 2718, 1740, 1710, 1603 cm–1;
1H NMR δ ppm 2.01 (s, 3H, –COCH3), 3.16 (dd, J=14.8 Hz, 1H,
ArC–H), 3.48 (dd, J=14.6 Hz, 1H, ArC H),3.90 (s, 6H, 2×–OCH3,),
5.78 (dd, J=8.6 Hz, 1H, O–CH), 6.50 (bs, 1H, ArH), 6.73 (bs, 1H,
ArH),7.10–7.35 (m, 5H, Ar H), 10.48 (s,1H, –CHO); 13C NMR δ ppm,
21.2 (CH3), 36.2 (CH2), 55.3 (2CH3), 78.9 (CH), 100.1 (CH), 104.3 (CH),
127.6 (2CH), 128.4 (2CH), 129.1 (2CH), 140.2 (C), 143 (C), 162.1 (C),
167.4 (C), 168.8 (C=O), 188.8 (C=O). Anal. calcd for C19H20O5: 69.50;
H, 6.14; found: C, 69.420; H, 6.19%.
2-(2-Formyl-3,5-dimethoxyphenyl)-1-(4-methoxyphenyl)ethylacetate
(19): Yellowish oil; yield 0.54 g (75%); IR (neat):2710, 1740, 1715 cm–1;
1H NMR δ ppm 2.01 (s, 3H, –COCH3), 3.16 (dd, J=14.8 Hz, 1H,
Ar–CH), 3.48 (dd, J=14.6 Hz, 1H, Ar–CH), 3.82 (s, 3H, –OCH3),
3.90(bs, 6H, –OCH3), 5.78 (dd, J=8.6 Hz, 1H, Ar–CH–O), 6.50 (bs, 1H,
ArH), 6.73 (bs, 1H, ArH), 7.10(d, J=8 Hz, 2H, ArH), 7.35 (d, J=8 Hz,
2H, ArH), 10.55 (s, 1H, –CHO); 13C NMR δ ppm 23.2 (CH3), 36.5 (CH2),
56.6 (3CH3), 80.6 (CH), 99.8 (CH), 104.4 (CH), 111.2 (C), 114.6 (2CH),
128.3 (2CH), 133.4 (C), 143.8 (C), 159.3 (C), 162.2 (C), 167.5 (C), 170.3
(C=O), 188.3 (CHO); Anal. calcd for C20H22O6: C, 67.04; H, 6.19; found:
C, 67.16; H, 6.27%.
2-(2-Formyl-3,5-dimethoxyphenyl)-1-(3,4-dimethoxyphenyl)ethyl
acetate (20): Pale yellow oil; yield 0.57 g (76%); IR (neat): 2700, 1735,
1695 cm–1; 1H NMR δ ppm 2.03 (s, 3H, –COCH3), 3.48 (dd, J=14.6 Hz,
1H, ArCH), 3.75 (dd, J=14.8 Hz, 1H, ArCH), 3.90 (s, 6H, –OCH3),
4.15 (s, 6H, –OCH3), 5.90 (dd, J=8.6 Hz, 1H, Ar–CH–O), 6.40 (bs, 1H,
ArH), 6.78 (bs, 1H, ArH), 7.15–7.45 (m, 3H, ArH), 10.53 (s, 1H, –CHO);
13C NMR δ ppm 21.1 (CH3), 36.6 (CH2), 55.3 (2CH3), 56.6 (3CH3), 79.6
(CH), 100.2 (CH), 104.6 (CH), 111.3 (C), 112.3 (CH), 115.6 (CH), 120.2
(CH), 134.4 (C), 144.6 (C), 148.1 (C), 150.1 (C), 162.3 (C), 170.1 (C=O),
188.7 (CHO). Anal. calcd for C21H24O7, C, 64.94; H, 6.23; found: C,
64.82; H, 6.35%.
(CH), 104 (CH), 105.2 (C), 112.3 (CH), 16.6 (CH), 120.2 (CH), 134.1
(C), 143 (C), 148.2 (C), 150 (C), 162.8 (C), 164.8 (C), 169 (C=O). Anal.
calcd for C19H20O6: C, 66.27; H, 5.85; found: C, 66.35; H, 5.94%.
We are grateful to Principal Dr S.G. Gupta for making available
laboratory facilities and DST‑FIST for instrumentation support.
RAL thanks UGC for providing Junior Research Fellowship,
Department of Chemistry, Savitribai Phule Pune University for
spectral analysis. Thanks are also due to Dr R.C. Chikate and Dr
V.B. Kumbhar for helpful discussions.
Received 5 November 2015; accepted 23 February 2015
Paper 1403003 doi: 10.3184/174751915X14258938697567
Published online: 13 April 2015
References
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Oxidative cyclisation reaction; general procedure
The aldehyde 18–20 (2.5 mmol) was dissolved in a mixture of
1,4‑dioxane (50 mL) and water (10 mL) and heated to 80 °C. To this
mixture was then added a solution of KMnO4 (21 mmol) in water
(50 mL) within 10 minutes under vigorous stirring. After completion of
the addition, stirring was continued at 80 °C for 45 minutes. The reaction
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purified on column chromatography to provide the desired products.
6,8-Dimethylmontroumarin (21): White solid; yield 0.44 g (65%); m.p.
162 °C (lit.31 160–162 °C); IR(KBr):1755, 1610 cm–1; 1H NMR δ ppm 3.10
(dd, J=16.4 & 3.9 Hz, 1H, C4‑H), 3.26 (dd, J=16.4 & 11 Hz, 1H, C4‑H),
3.85 (s, 3H, –OCH3), 3.94 (s, 3H, –OC H3), 5.42 (dd, J=11.0 & 3.9 Hz,
1H, C3‑H), 6.33 (d, J=2.1 Hz, 1H, C7‑H), 6.45 (d, J=2.2 Hz, 1H, C5‑H),
7.21–7.30 (m, 3H, ArH), 7.47 (d, J=7.2 Hz, 2H, ArH); 13C NMR δ ppm
35.7 (CH2), 55.7 (CH3), 56.4 (CH3), 78.6 (CH), 97.8 (CH), 103.9 (CH),
107.2 (C), 126.7 (2CH), 128.9 (CH), 129.3 (2CH), 141.21 (C), 144.08 (C),
162.87 (C), 163.05 (C), 164.89 (CO). Anal. calcd for C17H16O4: C, 71.82;
H, 5.67; found: C, 71.70; H, 5.78%.
6,8,4′-Trimethylthunberginol C (22): Cream coloured solid; yield
0.52 g (68%); m.p. 160 °C; IR (KBr): 1755, 1612 cm–1; 1H NMR δ ppm
3.00 (dd, J=14.8 Hz, 1H, C4‑H), 3.26 (dd, J=14.6 Hz, 1H, C4‑H), 3.76
(s, 6H, –OCH3), 3.88 (s, 3H, –OCH3), 5.94 (dd, J=8.6 Hz, 1H, C3‑H),
6.32 (bs, 1H, C7‑H), 6.79 (bs, 1H, C5‑H), 7.12 (d, J=8 Hz, 2H, C3′ &
C5′‑H), 7.30 (d, J=8 Hz, 2H, C2′ & C6′‑H); 13C NMR δ ppm 36.4 (CH2),
55.7 (3CH3), 80.2 (CH), 97.4 (CH), 104.1 (CH), 105.7 (C), 114.2 (2CH),
128.6 (2C), 133.1 (C), 144.4 (C), 159.3 (C), 162.6 (C), 166.2 (C), 169.0
(C=O). Anal. calcd for C18H18O5: C, 68.78; H, 5.78; found: C, 68.62; H,
5.85%.
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6,8,2′,3′-Tetramethylthunberginol D (23): White solid; yield 0.6 g
1
(70%); m.p.176ꢀ°C; IR (KBr): 1755. 1610 cm–1; H NMR δ ppm 3.01
(dd, J=14.6 Hz, 1H, C4‑H), 3.26 (dd, J=14.8 Hz, 1H, C4‑H), 3.95
(s, 6H, –OCH3), 4.16 (s, 6H, –OCH3), 5.90 (dd, J=8.6 Hz, 1H, C3‑H),
6.31(bs, 1H, C7‑H), 6.80(bs, 1H, C5‑H), 6.95–7.25(m, 3H, ArH);
13C NMR δ ppm 33.2 (CH2), 55.4 (2CH3), 56.6 (2CH3), 79.8 (CH), 100.3
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