B130413_1070.pdf

1070 Bull. Korean Chem. Soc. 2013, Vol. 34, No. 4 Priya Mishra et al.

http://dx.doi.org/10.5012/bkcs.2013.34.4.1070

Novel Synthesis of 3-Phenyl-chromen-4-ones Using N-Heterocyclic Carbene as

Organocatalyst: An Efficient Domino Catalysis Type Approach

Priya Mishra, Sarita Singh, Preyas Ankit, Shahin Fatma, Divya Singh, and Jagdamba Singh*

Environmentally Benign Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad-211002, India*E-mail: [email protected]

Received November 22, 2012, Accepted January 9, 2013

Herein is reported a simple and efficient synthesis of isoflavones starting from various substituted phenacyl

bromides and salicylaldehydes in presence of NHC. The mechanism involved domino catalysis type approach

with consumption and regeneration of catalyst in two catalytic cycles. This method proved to be very lucrative

and gives very good yield. The method described here represents an environmentally benign alternative to

classical approach.

Key Words : Umpolung, Heterocycles, Thiamine (N-Heterocyclic carbene), Domino catalysis, Natural Prod-

ucts

Introduction

One of the major issues of modern chemistry is the

development of efficient methodologies for the synthesis of

bioactive compounds including natural products and their

analogues.1 Further, novel methodologies can be acceptable

if, in addition to appropriate product yields, they avoid the

use of toxic reagents and solvents, involve catalytic trans-

formations and reduce the amount of waste by-products.

Recently, much emphasis has been given to “one pot” pro-

cesses involving multiple catalytic transformations followed

by a single work-up stage. Generally, these processes paved

a way to improve synthetic efficiency and allow the formation

of complex compound from simple substrates through two

or more individual elaborations without isolation of inter-

mediate compounds. This tandem methodology is now

becoming more and more popular in the synthesis of many

complex organic molecules including various heterocyclic

systems.2

Isoflavones (3-aryl-chromen-4-ones) (Fig. 1), a major

class of natural products, also comprise an important group

of medicinal compounds. They are found in many plants and

are especially abundant in legumes (fabaceae), such as soya,

lentils, chick pea, fenugreek, clovers and alfalfa.3

Isoflavone and its derivatives possess a wide range of bio-

logical activities including antimicrobial,4 antioxidant,5,6

stimulating nerve growth,4 insecticidal activities,7 anti-osteo-

porotic,8 hypolipidemic activities,9 antitumor,10,11 anticataracts,12

anti-inflammatory13 and antifertility activities.14 It has also

been reported that isoflavones are effective in human obesity

and have a positive influence on plasma cholesterol.15

Recently, a number of isoflavones have been reported as

inhibitors of interleukin-5(IL-5),16,17 which is a proven target

for finding new therapeutics for eosinophilia associated

allergic inflammation.18,19 Due to their remarkably rich bio-

logical activities and excellent pharmacological properties,

isoflavone-based compounds have been the target of a great

deal of research into their synthesis.20

Most of the isoflavones have been isolated from natural

sources and their simple structural features lead to the

development of many synthetic methods. However, most of

the available methods utilize specific and expensive reagents

in large excess to achieve the reported yield. Long reaction

time, vigorous conditions, very low yield of the desired

product and unwanted reaction by-products, which require

laborious purification of the final product are some of the

major drawbacks of these methods. These conventional

methods are based on two strategies- the former is deoxy-

benzoin route21 wherein the deoxybenzoin is treated with a

one carbon activated system like N,N'-dimethyl formamide

dimethyl acetal followed by ring closure leading to the

formation of isoflavone and latter one, the chalcone route,22

which involves the conversion of a chalcone to isoflavone

by oxidative rearrangement using reagents like thallium

nitrate. Other methods like the hypervalent iodine oxidation

of flavanone,23a epoxidation of the chalcone followed by

rearrangement and debenzylative cyclization,23b palladium

catalysed cross coupling reaction of 3-bromochromone with

arylboronic acid23c and by the condensation of enamine with

salicylaldehyde23d are also used for the synthesis of iso-

flavones. In agreement to various benign aspects regarding

methodology adopted and environment and economic con-

cerns, literature demands the application of metal ion free,

environmentally safe, biodegradable and convenient reagents

in synthesis of these compounds. Additionally, it will be

better to design a programmed approach that involves the

concept of ‘catalyst economy’, where a catalyst or precatayst

is used more than once during a given synthetic sequence.24Figure 1. General Structure of Isoflavones.

Novel Synthesis of 3-Phenyl-chromen-4-ones Using N-Heterocyclic Carbene Bull. Korean Chem. Soc. 2013, Vol. 34, No. 4 1071

This catalysis approach can be positively coupled with

tandem or domino (cascasde) transformations as can be seen

in case of present work. The preferred catalyst, thiamine, in

this work is a non-flammable, inexpensive, biodegradable,

non-toxic and metal ion free reagent, which contains a

pyrimidine ring and a thiazole ring linked by a methylene

bridge.25 Hydrogen on the carbon between S and N (i.e. the

position 2) is acidic enough to be removed by the base which

allows several reactions26 in our body and other living

organisms that include decarbonylation of pyruvic acid to

acetaldehyde, conversion of pyruvic acid to acetoin,27 etc.

Thiamine analogues have been used as powerful organo-

catalyst for many carbon-carbon and carbon-heteroatom

bond formation reactions in good yield. Besides their bio-

chemical reactions, they have broad applications in synthetic

organic chemistry, which include Benzoin condensation,28

azabenzoin condensation,29 Stetter reaction,30 intramolecular

Stetter reaction,31 Stetter Pall-Knorr reaction32 and coupling

reaction of aldehyde-ketones33 etc.

As a part of the ongoing interest in thiamine-catalysed

reactions for various organic transformations, we had the

opportunity to further explore its catalytic activity towards

the synthesis of isoflavones for the first time. With the

elucidation of active species of thiamine as a nucleophilic

carbene/zwitterions (Scheme 1), our investigation has been

focused on using a non-enzymatic thiazolium based N-

heterocyclic caebene (NHC) as an organo catalyst in the

present synthesis. Thiamine as NHC has got the right balance

of nucleophilicity, ability to stabilize the intermediate and is

a good leaving group.34

The chemistry of N-heterocyclic carbenes (NHCs) has

grown dramatically since the first isolation of the stable

NHCs by Arduengo in 1991.35 They have been widely ap-

plied for the synthesis of heterocycles,36 used as ligands for

organometallic catalysts,37 and eventually developed into

nucleophilic organocatalyst.38 Owing to their capability to

attack as a nucleophile to the carbon-oxygen double bond of

aldehydes, not only the NHC-catalysed classical umpolung

of aldehydes for the Benzoin reactions and the Stetter reac-

tions, but also the NHC-catalysed “extended-umpolung” of

functionalized aldehydes39 such as α,β-unsaturated aldehydes,40

α-halo aldehydes,41 α,β-epoxyaldehydes42 and cyclopropane-

carboxaldehydes43 were demonstrated very successfully in

the past few years. We found NHCs (as thiazolium ions) a

competent basic, soft nucleophile, as well as reusable eco-

friendly species in the preparation of large number of iso-

flavones, with considerably reduced time and enhanced

efficiency. In this paper, a mild synthetic method has been

reported that can be used to obtain a series of 3-aryl iso-

flavones 3 efficiently by using thiamine as an organo-

catalyst. The method involves one pot reaction of phenacyl

bromides 1 with salicylaldehydes 2 in the presence of

catalytic amount of thiamine in ethanol at room temperature

(Scheme 2).

The mechanism operates through the domino catalysis

type method (‘domino catalysis’ due to Fogg et al.44), which

involves multiple cyclic transformations via a fundamentally

single catalytic mechanism.

Results and Discussion

Initially, we studied the reaction of phenacyl bromide 1a

(2.5 mmol) with salicylaldehyde 2a (2.5 mmol) in the

presence of 5 mol % thiamine in 4 mL ethanol at room

temperature for 12 h to give the desired product 3a in 30%

yield. However, no reaction has taken place when the

mixture was stirred under similar conditions in the absence

of thiamine even after 24 h (Table 1, entry 1). Encouraged by

the results, we further investigated the best reaction condi-

tions by using different amounts of thiamine. An increase in

the quantity of thiamine from 0 mol % to 25 mol % had not

only decreased the reaction time from 24 h to 1 h, but it also

had increased the product yield from 20% to 88% (Table 1,

entries 1-6). However, the yield did not increase when ex-

cess amount (30 mol %) of thiamine was used in this

reaction under the same conditions. Therefore, 25 mol %

thiamine was found sufficient to catalyze this reaction.

The activity of the recycled thiamine was also examined

under typical experimental conditions. After the completion

of reaction, as indicated by TLC, the desired product was

extracted in ethyl acetate, and the recovered catalyst was

further treated with the reactants following which the

product 3a was obtained in 88, 86, 80% yield after 1-3 runs

respectively (Table 1, entry 6). This study demonstrated that

thiamine could be effectively used as a reusable catalyst for

this synthesis. The model reaction of phenacyl bromide 1a

and salicylaldehyde 2a catalyzed by thiamine was then

Scheme 1

Scheme 2. Synthesis of Isoflavones 3.


chosen for investigating the effect of solvent (Table 2). As

shown in Table 2, low yields of target product 3a (32-55%)

were obtained when the mixture was stirred at room temper-

ature for 2 h in the presence of 25 mol % thiamine in THF,

Toluene, DCM and DMF (Table 2, entries 1, 2, 4, 5). The

reaction using ethanol as a solvent gave the corresponding

product 3a in high yield (88%) within short reaction time

(Table 2, entry 6). From the economical and environmental

point of view, ethanol was chosen as the reaction medium

for all further reactions.

Furthermore, encouraged by these results, various NHCs

generated from the corresponding precursors and one equi-

valent of base, were screened. It was found that among all

the NHCs screened, imidazolylidene 4, imidazolinylidene 5,

and triazolylidenes 6, 7 could catalyze the reaction but

results in only low to moderate yields of product.

Therefore, the best reaction conditions can be achieved by

using 25 mol % of thiamine as catalyst in ethanol at room

temperature.

To examine the extent of the catalyst’s application in this

reaction, we applied the optimized reaction conditions to a

series of phenacyl bromides and salicylaldehydes in the pre-

sence of 25 mol % thiamine in ethanol at room temperature

(Table 3). In all of the derivatives studied, it was observed

that electron-withdrawing substituent on the phenacyl bromide

influenced the reaction and furnished the corresponding

isoflavone in good yield (Table 3, entry c), whereas the

electron-rich substituent on the phenacyl bromide gave com-

paratively low yield of isoflavone under identical conditions

(Table 3, entry b). Further, it was also observed that the

presence of electron rich substituent para to hydroxy group,

i.e., R2 on the salicylaldehyde had also furnished the corre-

sponding isoflavone in comparatively good yield (Table 3,

entry j). On the other hand presence of such electron-rich

substituents para or ortho to aldehydic group, i.e., R1 or R3

on the salicylaldehyde gave the corresponding isoflavones in

comparatively low yields (Table 3, entries d, e and k, l).

We propose a mechanism of the thiamine catalyzed reac-

Table 1. Reaction of Phenacyl Bromide 1a and Salicylaldehyde 2ain the presence of Thiaminea

Entry Catalyst (mol %) Time (h) Yield of 3ab (mol %)

1 0 24 No reaction

2 5 12 35

3 10 8 45

4 15 5 62

5 20 3 75

6c 25 1 88, 86, 80

7 30 1 88

aConditions: phenacyl bromide 1a (2.5 mmol), and salicylaldehyde 2a(2.5 mmol), Ethanol (4 mL), stirring (rt). bIsolated Yields. cCatalyst wasreused two times (1-3 catalytic runs).

Table 2. Reaction of phenacyl bromide 1a and salicylaldehyde 2ain different solventsa

Entry Solvent Time (h)Yield of 3ab

(mol %)

1 THF 2 32

2 Toluene 2 45

3 MeCN 2 68

4 DCM 2 50

5 DMF 2 55

6 Ethanol 1 88

aConditions: phenacyl bromide 1a (2.5 mmol), and salicylaldehyde 2a(2.5 mmol), thiamine (0.6 mmol, 25 mol %), solvent (4 mL), stirring (rt).b Isolated Yields.

Table 3. Synthesis of isoflavones 3 catalyzed by thiaminea

Entry R R1 R2 R3

Time

(min)

Isoflavone (3)

Yield (%)bmp [oC]

(Observed)

a H H H H 60 88 150-155

b OCH3 H H H 90 85 220-222

c NO2 H H H 30 92 195-198

d H OH H H 80 85 210-213

e H OCH3 H H 85 80 157-159

f OH OH H H 90 82 320

g OCH3 OH H H 90 80 257-258

h OH OCH3 H H 88 80 218-220

i OCH3 OCH3 H H 95 70 162-164

j OH H OH H 85 88 160-162

k OH H H OH 90 82 168-170

l OCH3 H H OH 95 80 140-142

m OH OH H OH 95 75 295

n OCH3 OH H OH 120 65 211-212

aConditions: phenacyl bromide 1a (2.5 mmol), and salicylaldehyde 2a(2.5 mmol), thiamine (0.6 mmol, 25 mol %), Ethanol (4 mL), stirring (r.t.), bIsolated Yields.


tion as shown in Scheme 3. It is a domino catalysis type

scheme involving two catalytic cycles, A and B. Cycle A

involves nucleophilic attack of thiamine (thiazolium ion) to

carbonyl carbon of phenacyl bromide 1, followed by intra-

molecular nucleophilic substitution to give intermediate 9.45

This intermediate 9 reacts with salicylaldehyde 2 to give 10

with regeneration of catalyst. The regenerated catalyst again

reacts with intermediate 10 to initiate the catalytic cycle B.

the initiation of cycle B results in the phenomenon of

reversal of polarity/umpolung at aldehydic carbon to give

11.28,30,46 Following this, 11 undergoes intramolecular nucleo-

philic addition (cyclization) followed by eventual regene-

ration of catalyst to give 13. Intermediate 13 then undergoes

dehydration to give the desired product 3.

Hence, it is evident from proposed mechanism that the

reagents undergo several transformations without isolation

of intermediates (one-pot approach). Though the two cata-

lytic cycles seem different (cycle B involves cyclization), the

mode of action of catalyst is same (i.e., it acts as nucleo-

phile). Therefore, the fundamental mechanism is same in

both the cycles (domino catalysis).

Conclusion

In summary, we have developed an efficient and conv-

enient domino catalysis type approach for the synthesis of

isoflavones (3-aryl-chromen-4-ones) via the reactions of

phenacyl bromides 1 and salicylaldehydes 2 catalyzed

by thiamine (NHC) in ethanol at room temperature. The

entire synthesis was carried out under varying experimental

conditions including amount of catalyst and range of solv-

ents in order to achieve optimum reaction condition. The

operational simplicity, mild reaction conditions, short reac-

tion time and catalyst economy with minimal environmental

impact are notable features of this procedure. Hence, it is an

environmentally benign alternative to the existing conven-

tional methods.

Experimental

To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6

mmol) was dissolved in 0.64 mL of water and added 2.4 mL

of 95% ethanol (water : 95% ethanol = ~1:4). The solution

was cooled in an ice bath, then added 0.40 mL of 3 M NaOH

(1.2 mmol) dropwise with stirring in a manner such that the

temperature remained below 20 oC. Intense yellow coloured

solution changed to pale yellow solution of thiamine

(thiazolium ion)/N-heterocyclic carbene (Scheme 1).47

In a 25-mL round bottom flask, a mixture of phenacyl

bromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6

mmol, 25 mol %) in ethanol (4 mL) was stirred at room

temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol,

0.26 mL in case of 2a) was added slowly and the mixture

was stirred at room temperature until the reaction was

completed (as monitored by TLC) (Table 3) . The reaction

mixture was then poured into 20 mL of distilled water and

extracted with ethyl acetate (3 × 10 mL). The organic layer

was dried over anhydrous Na2SO4 and the solvent was

Scheme 3. Plausible mechanistic pathway.


removed under reduced pressure. The resulting product

isoflavone 3 was further purified either by recrystallization

or by column chromatography (Ethyl acetate:Hexane, 1:4

v/v). All compounds were characterized by their mp and 1H-

NMR, 13CNMR and mass spectral data.

The melting points were determined on a MAC, DIGITAL

MELTING POINT APPARATUS and were uncorrected. 1H

(400 MHz) and 13C (100 MHz) spectra were recorded on a

Bruker Avance II 400 spectrometer. The chemical shifts are

expressed in ppm: s, singlet; d, doublet; t, triplet; m, multi-

plet. The products were purified either by recrystallization or

by column chromatography. The starting materials used

were purchased from Aldrich Chemical Company and were

used without any further purification. Elemental analyses

were performed using a Vario EL III CHN-O- analyzer.

3-Phenyl-chromen-4-one (3a). Pale yellow crystal, mp

150-155 oC; 1H-NMR (400 MHz, DMSO-d6) δH 8.45 (s,

1H), 8.00 (d d, J = 8.50 Hz, 1.70 Hz, 1H), 7.65 (t, J = 7.46

Hz, 1H), 7.48 (d d, J = 8.05 Hz, 1.66 Hz, 1H), 7.40 (t, J =

7.45 Hz, 1H), 7.28 (t, J = 7.60 Hz, 2H), 7.25 (t, J = 7.40 Hz,

8.00 Hz, 1H), 7.22 (d d, J = 7.90 Hz, 1.67 Hz, 2H). 13C NMR

(100 MHz, DMSO-d6) δc 175.5, 157.1, 153.4, 135.5, 132.3,

130.2, 128.9, 128.1, 126.2, 124.1, 123.4, 123.1, 117.5.

EIMS (m/z): 222 (M+). Anal. Calc. for C15H10O2; C, 81.07;

H, 4.54; O, 14.40. Found: C, 81.04; H, 4.56; O, 14.45.

3-(4-Methoxy-phenyl)-chromen-4-one (3b). Yellow crystal,

mp 220-222 oC; 1H-NMR (400 MHz, DMSO-d6) δH 8.73 (s,

1H), 8.02 (d d, J = 8.60 Hz, 2.12 Hz, 1H), 7.40 (d d, J = 7.95

Hz, 2.00 Hz, 1H), 7.36 (m, 3H), 7.28 (t, J = 7.50 Hz, 1H),

6.86 (d, J = 7.77 Hz, 2H), 3.65 (s, 3H). 13C NMR (100 MHz,

DMSO-d6) δc 175.5, 160.1, 157.2, 153.1, 135.6, 130.3,

127.3, 125.1, 124.1, 123.6, 123.2, 117.5, 114.3, 56.2. EIMS

(m/z): 252 (M+). Anal. calc. for C15H10O2; C, 76.18; H, 4.79;

O, 19.03. Found: C, 76.20; H, 4.80; O, 19.01.

3-(4-Nitro-phenyl)-chromen-4-one (3c). Orange solid,


1H), 8.27 (d, J = 7.75 Hz, 2H), 7.99 (d d, J = 8.05 Hz, 1.79

Hz, 1H), 7.65 (d, J = 7.63 Hz, 2H), 7.50 (d d, J = 8.00 Hz,

1.72 Hz, 1H), 7.41 (t, J = 7.56 Hz, 1H), 7.32 (t, J = 7.49 Hz,

1H). 13C NMR (100 MHz, DMSO-d6) δc 170, 157.06, 155.03,

149.14, 143.33, 135.17, 130.33, 127.37, 126.53, 126.46,

126.01, 126.0, 118.61. EIMS (m/z): 267 (M+). Anal. Calc.

for C15H10O2; C, 67.42; H, 3.39; N, 5.24; O, 23.95. Found:

C, 67.40; H, 3.41; N, 5.25; O, 23.93.

7-Hydroxy-3-phenyl-chromen-4-one (3d). White solid,


1H), 8.90 (s, 1H), 7.88 (d, J = 7.57 Hz, 1H), 7.50 (d d, J =

8.40 Hz, 1.83 Hz, 2H), 7.28 (t, J = 7.52 Hz, 2H), 7.20 (t, J =

7.43 Hz, 1H), 6.92 (s, 1H), 6.75 (d d, J = 8.20 Hz, 1.60 Hz,

1H). 13C NMR (100 MHz, DMSO-d6) δc 172.25, 161.86,

156.96, 153.03, 132.24, 127.74, 127.69, 127.14, 126.60,

124.0, 116, 115.63, 101.14. EIMS (m/z): 238 (M+). Anal.

Calc. for C15H10O2; C, 75.62; H, 4.23; O, 20.15. Found: C,

75.63; H, 4.25; O, 20.11.

7-Methoxy-3-phenyl-chromen-4-one (3e). White solid,


1H), 7.90 (d, J = 7.51 Hz, 1H), 7.52 (d d, J = 8.42 Hz, 1.67

Hz, 2H), 7.33 (t, J = 7.60 Hz, 2H), 7.21 (t, J = 7.48 Hz, 1H),

6.90 (d, J = 1.47 Hz, 1H), 6.80 (d d, J = 8.48 Hz, 1.62 Hz,

1H), 3.62 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δc

171.25, 162.31, 154.71, 152.03, 131.24, 126.74, 125.21,

124.69, 124.14, 122.0, 116.82, 112.56, 99.11, 54.04. EIMS

(m/z): 252 (M+). Anal. Calc. for C15H10O2; C, 76.18; H, 4.79;

O, 19.03. Found: C, 76.15; H, 4.81; O, 19.05.

7-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (Dai-

dzin) (3f). Pale yellow crystal, mp 320-321 oC; 1H-NMR

(400 MHz, DMSO-d6) δH 9.32 (s, 1H), 9.27 (s, 1H), 8.51 (s,

1H), 7.84 (d, J = 7.68 Hz, 1H), 7.05 (d, J = 7.61 Hz, 2H),

6.95 (s, 1H), 6.78 (d, J = 7.53 Hz, 2H), 6.75 (d d, J = 8.59

Hz, 1.71 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δc 175.4,

165.1, 158.5, 157.9, 153.4, 132.1, 127.7, 125.1, 123.7,

116.6, 115.5, 110.8, 105.3. EIMS (m/z): 254 (M+). Anal.

Calc. for C15H10O2; C, 70.86; H, 3.96; O, 25.17. Found: C,

70.83; H, 3.97; O, 25.19.

7-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-one (Form-

ononetin) (3g). Colourless needles, mp 255-257 oC; 1H-

NMR (400 MHz, DMSO-d6) δH 9.26 (s, 1H), 8.80 (s, 1H),

7.84 (d, J = 7.59 Hz, 1H), 7.37 (d, J = 7.69 Hz, 2H), 6.92 (s,

1H), 6.83 (d, J = 7.58 Hz, 2H), 6.75 (d d, J = 8.28 Hz, 1.56

Hz, 1H), 3.64 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δc

169.25, 158.86, 154.89, 153.96, 150.03, 125.57, 123.60,

121.0, 120.05, 113.0, 112.63, 109.94, 98.14, 54.04. EIMS

(m/z): 268 (M+). Anal. Calc. for C15H10O2; C, 71.64; H, 4.51;

O, 23.86. Found: C, 71.61; H, 4.55; O, 23.82.

3-(4-Hydroxy-phenyl)-7-methoxy-chromen-4-one (3h).

White solid, mp 218-220 oC; 1H-NMR (400 MHz, DMSO-

d6) δH 9.31 (s, 1H), 8.78 (s, 1H), 7.85 (d, J = 7.59 Hz, 1H),

7.35 (d, J = 7.53 Hz, 2H), 6.90 (s, 1H), 6.80 (m, 3H), 3.67 (s,


154.92, 151.03, 148.71, 126.95, 124.21, 122.0, 119.81,

115.82, 111.97, 111.56, 98.11, 53.04. EIMS (m/z): 268 (M+).

Anal. Calc. for C15H10O2; C, 71.64; H, 4.51; O, 23.86. Found:

C, 71.65; H, 4.55; O, 23.87.

7-Methoxy-3-(4-methoxy-phenyl)-chromen-4-one (3i).

White solid, mp 162-164 oC; 1H-NMR (400 Hz, DMSO-d6)

δH 8.80 (s, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.40 (d, J = 7.62

Hz, 2H), 6.94 (s, 1H), 6.82 (m, 3H), 3.69 (s, 3H), 3.64 (s,


157.89, 155.71, 153.03, 128.57, 126.20, 124, 123.05, 117.82,

113.56, 112.94, 100.11, 55.04, 55.03. EIMS (m/z): 282 (M+).

Anal. Calc. for C15H10O2; C, 72.33; H, 5.00; O, 22.67.

Found: C, 72.30; H, 5.1; O, 22.65.

6-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (3j).

White solid, mp 160-162 oC; 1H-NMR (400 MHz, DMSO-

d6) δH 9.30 (s, 1H), 9.17 (s, 1H), 8.80 (s, 1H), 7.52 (s, 1H),

7.36 (d, J = 7.71 Hz, 2H), 7.28 (d, J = 7.80 Hz, 1H), 6.85 (d

d, J = 8.85 Hz, 1.52 Hz, 1H), 6.80 (d, J = 7.81 Hz, 2H). 13C

NMR (100 MHz, DMSO-d6) δc 175.5, 157.8, 153.2, 153.1,

150.1, 127.9, 125.3, 125.1, 123.6, 122.6, 119.2, 116.5, 115.9.

EIMS (m/z): 254 (M+). Anal. Calc. for C15H10O2; C, 70.86;

H, 3.96; O, 25.17. Found: C, 70.85; H, 3.99; O, 25.19.

5-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (3k).

Crystalline solid, mp 168-170 oC, 1H-NMR (400 MHz,

DMSO-d6), δH 9.35 (s,1H), 9.27 (s, 1H), 8.83 (s, 1H), 7.35


(d, J = 7.57 Hz, 2H), 7.20 (t, J = 7.49 Hz, 1H), 7.00 (d d, J =

8.57 Hz, 1.69 Hz, 1H), 6.81 (d, J = 7.58 Hz, 2H), 6.76 (d d, J

= 8.68 Hz, 1.62 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δc

175.5, 162.6, 158.8, 157.9, 153.1, 136.8, 127.8, 125.1,

123.6, 115.9, 112.8, 110.5, 110.1. EIMS (m/z): 254 (M+).

Anal. Calc. for C15H10O2; C, 70.86; H, 3.96; O, 25.17. Found:

C, 70.82; H, 3.99; O, 25.17.

5-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-one (3l).

Crystalline solid, mp 140-142 oC; 1H-NMR (400 MHz,

DMSO-d6) δH 9.34 (s,1H), 8.78 (s, 1H), 7.35 (d, J = 7.66 Hz,

2H), 7.19 (t, J = 7.43 Hz, 1H), 7.02 (d d, J = 8.62 Hz, 1.61

Hz, 1H), 6.83 (d, J = 7.66 Hz, 2H), 6.80 (d d, J = 8.71 Hz,

1.58 Hz, 1H), 3.65 (s, 3H). 13C NMR (100 MHz, DMSO-d6)

δc 175.4, 162.5, 160.1, 158.8, 153.4, 136.9, 127.5, 125.1,

123.6, 114.1, 113.1, 110.5, 110.2, 55.8. EIMS (m/z): 268

(M+). Anal. Calc. for C15H10O2; C, 71.64; H, 4.51; O, 23.86.

Found: C, 71.63; H, 4.53; O, 23.89.

5,7-Dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-one

(Genistein) (3m). Off-white powder, mp 295 oC; 1H-NMR

(400 MHz, DMSO-d6) δH 9.40-9.20 (s*, 3H), 8.78 (s, 1H),

7.33 (d, J = 7.72 Hz, 2H), 6.81 (d, J = 7.67 Hz, 2H), 6.54 (s,

1H), 6.25 (s, 1H). *three nearly overlapped singlets. 13C NMR

(100 MHz, DMSO-d6) δc 176.03, 161.88, 157.41, 155.83,

154.92, 151.71, 126.95, 122.56, 119.81, 111.97, 101.92,

96.33, 90.78. EIMS (m/z): 270 (M+). Anal. Calc. for C15H10O2;

C, 66.67; H, 3.73; O, 29.60. Found: C, 66.66; H, 3.75; O,

29.62.

5,7-Dihydroxy-3-(4-methoxy-phenyl)-chromen-4-one

(Biochanin A) (3n). Tan powder, mp 211-212 oC; 1H-NMR

(400 MHz, DMSO-d6) δH 9.28-9.35 (s*, 2H), 8.77 (s, 1H),

7.35 (d, J = 7.53 Hz, 2H), 6.88 (d, J = 7.50 Hz, 2H), 6.58

(s,1H), 6.20 (s, 1H), 3.66 (s, 3H). *two overlapped singlets.13C NMR (100 MHz, DMSO-d6) δc 183.03, 168.88, 165.92,

162.89, 162.83, 158.71, 133.57, 133.56, 128.05, 117.94,

108.92, 103.33, 97.78, 60.04. EIMS (m/z): 284 (M+). Anal.

Calc. for C15H10O2; C, 67.60; H, 4.25.; O, 28.14. Found: C,

67.63; H, 4.21; O, 28.13.

Acknowledgments. We sincerely thank SAIF, Punjab

University, Chandigarh for providing micro analysis and

spectra. The authors are also greatful to CSIR and UGC,

New Delhi for the award of Senior Research Fellowship

(SRF). And the publication of this paper was supported by

the Korean Chemical Society.

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