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1070 Bull. Korean Chem. Soc. 2013, Vol. 34, No.

4
http://dx.doi.org/10.5012/bkcs.2013.34.4.1070

Priya Mishra et al.

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: dr.jdsau@gmail.com
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 Products

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 transformations and reduce the amount of waste by-products.
Recently, much emphasis has been given to “one pot” processes 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 intermediate 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 biological activities including antimicrobial,4 antioxidant,5,6
stimulating nerve growth,4 insecticidal activities,7 anti-osteoporotic,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

Figure 1. General Structure of Isoflavones.

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 biological 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 deoxybenzoin 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 isoflavones. In agreement to various benign aspects regarding
methodology adopted and environment and economic concerns, 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.24

as indicated by TLC. We found NHCs (as thiazolium ions) a competent basic.30 intramolecular Stetter reaction. which contains a pyrimidine ring and a thiazole ring linked by a methylene bridge. The preferred catalyst.27 etc. Besides their biochemical reactions. The activity of the recycled thiamine was also examined under typical experimental conditions. However.β-unsaturated aldehydes. with considerably reduced time and enhanced efficiency. Thiamine as NHC has got the right balance of nucleophilicity.34 The chemistry of N-heterocyclic carbenes (NHCs) has grown dramatically since the first isolation of the stable NHCs by Arduengo in 1991. 4 1071 Scheme 1 This catalysis approach can be positively coupled with tandem or domino (cascasde) transformations as can be seen in case of present work.25 Hydrogen on the carbon between S and N (i. 86.β-epoxyaldehydes42 and cyclopropanecarboxaldehydes43 were demonstrated very successfully in the past few years. Vol. ability to stabilize the intermediate and is a good leaving group. This study demonstrated that thiamine could be effectively used as a reusable catalyst for this synthesis.35 They have been widely applied for the synthesis of heterocycles. we studied the reaction of phenacyl bromide 1a (2. thiamine. biodegradable. conversion of pyruvic acid to acetoin.36 used as ligands for organometallic catalysts. 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. the desired product was extracted in ethyl acetate. in this work is a non-flammable. Thiamine analogues have been used as powerful organocatalyst for many carbon-carbon and carbon-heteroatom bond formation reactions in good yield. In this paper. 34.38 Owing to their capability to attack as a nucleophile to the carbon-oxygen double bond of aldehydes. our investigation has been focused on using a non-enzymatic thiazolium based Nheterocyclic caebene (NHC) as an organo catalyst in the present synthesis.44). 80% yield after 1-3 runs respectively (Table 1.41 α. no reaction has taken place when the mixture was stirred under similar conditions in the absence of thiamine even after 24 h (Table 1. entries 1-6). they have broad applications in synthetic organic chemistry. which involves multiple cyclic transformations via a fundamentally single catalytic mechanism.29 Stetter reaction.e. as well as reusable ecofriendly species in the preparation of large number of isoflavones.5 mmol) with salicylaldehyde 2a (2. entry 1). and the recovered catalyst was further treated with the reactants following which the product 3a was obtained in 88. entry 6).Novel Synthesis of 3-Phenyl-chromen-4-ones Using N-Heterocyclic Carbene Bull. Results and Discussion Initially. we had the opportunity to further explore its catalytic activity towards the synthesis of isoflavones for the first time. but also the NHC-catalysed “extended-umpolung” of functionalized aldehydes39 such as α.31 Stetter Pall-Knorr reaction32 and coupling reaction of aldehyde-ketones33 etc.40 α-halo aldehydes. 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. 2013. The mechanism operates through the domino catalysis type method (‘domino catalysis’ due to Fogg et al. No. soft nucleophile. After the completion of reaction. a mild synthetic method has been reported that can be used to obtain a series of 3-aryl iso- Scheme 2. Synthesis of Isoflavones 3.28 azabenzoin condensation. non-toxic and metal ion free reagent. As a part of the ongoing interest in thiamine-catalysed reactions for various organic transformations. inexpensive.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. Soc. The model reaction of phenacyl bromide 1a and salicylaldehyde 2a catalyzed by thiamine was then . Encouraged by the results. flavones 3 efficiently by using thiamine as an organocatalyst. Therefore. we further investigated the best reaction conditions by using different amounts of thiamine. 25 mol % thiamine was found sufficient to catalyze this reaction. With the elucidation of active species of thiamine as a nucleophilic carbene/zwitterions (Scheme 1). However. which include Benzoin condensation. but it also had increased the product yield from 20% to 88% (Table 1. Korean Chem. 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).37 and eventually developed into nucleophilic organocatalyst. the yield did not increase when excess amount (30 mol %) of thiamine was used in this reaction under the same conditions. not only the NHC-catalysed classical umpolung of aldehydes for the Benzoin reactions and the Stetter reactions.

. The reaction using ethanol as a solvent gave the corresponding product 3a in high yield (88%) within short reaction time (Table 2. R2 on the salicylaldehyde had also furnished the corresponding isoflavone in comparatively good yield (Table 3. it was also observed that the presence of electron rich substituent para to hydroxy group. stirring (rt). Synthesis of isoflavones 3 catalyzed by thiaminea a Conditions: phenacyl bromide 1a (2. chosen for investigating the effect of solvent (Table 2). Ethanol (4 mL).5 mmol). entry b).e. 34. 2013. Korean Chem. It was found that among all the NHCs screened. imidazolylidene 4.6 mmol. t. e and k. b Isolated Yields. entry j). low yields of target product 3a (32-55%) were obtained when the mixture was stirred at room temperature for 2 h in the presence of 25 mol % thiamine in THF. were screened. imidazolinylidene 5. 25 mol %). 2.5 mmol). entries 1. To examine the extent of the catalyst’s application in this reaction.1072 Bull. entry c). and salicylaldehyde 2a (2. i. Therefore. i. On the other hand presence of such electron-rich substituents para or ortho to aldehydic group. Table 2.5 mmol). Ethanol (4 mL).5 mmol).5 mmol). We propose a mechanism of the thiamine catalyzed reac- . and salicylaldehyde 2a (2. In all of the derivatives studied.6 mmol. various NHCs generated from the corresponding precursors and one equivalent of base. Table 3. entries d. encouraged by these results. 4. bIsolated Yields. it was observed that electron-withdrawing substituent on the phenacyl bromide influenced the reaction and furnished the corresponding isoflavone in good yield (Table 3. Reaction of phenacyl bromide 1a and salicylaldehyde 2a in different solventsa Entry Solvent Time (h) Yield of 3ab (mol %) 1 2 3 4 5 6 THF Toluene MeCN DCM DMF Ethanol 2 2 2 2 2 1 32 45 68 50 55 88 a Conditions: phenacyl bromide 1a (2.. Further. 25 mol %). No. l). solvent (4 mL). Reaction of Phenacyl Bromide 1a and Salicylaldehyde 2a in the presence of Thiaminea Entry Catalyst (mol %) Time (h) Yield of 3ab (mol %) 1 2 3 4 5 6c 7 0 5 10 15 20 25 30 24 12 8 5 3 1 1 No reaction 35 45 62 75 88. 80 88 Priya Mishra et al. we applied the optimized reaction conditions to a series of phenacyl bromides and salicylaldehydes in the presence of 25 mol % thiamine in ethanol at room temperature (Table 3). the best reaction conditions can be achieved by using 25 mol % of thiamine as catalyst in ethanol at room temperature. ethanol was chosen as the reaction medium for all further reactions. R1 or R3 on the salicylaldehyde gave the corresponding isoflavones in comparatively low yields (Table 3.e. Entry a b c d e f g h i j k l m n R R1 R2 R3 H H H H OCH3 H NO2 H H H OH H H OCH3 H OH OH H OCH3 OH H OH OCH3 H OCH3 OCH3 H OH H OH OH H H OCH3 H H OH OH H OCH3 OH H H H H H H H H H H H OH OH OH OH Time Isoflavone (3) mp [oC] (min) Yield (%)b (Observed) 60 90 30 80 85 90 90 88 95 85 90 95 95 120 88 85 92 85 80 82 80 80 70 88 82 80 75 65 150-155 220-222 195-198 210-213 157-159 320 257-258 218-220 162-164 160-162 168-170 140-142 295 211-212 a Conditions: phenacyl bromide 1a (2.). and triazolylidenes 6. 4 Table 1. stirring (r. Toluene. thiamine (0. DCM and DMF (Table 2. Vol. whereas the electron-rich substituent on the phenacyl bromide gave comparatively low yield of isoflavone under identical conditions (Table 3. bIsolated Yields. Soc. From the economical and environmental point of view. stirring (rt). thiamine (0. 86. As shown in Table 2. 7 could catalyze the reaction but results in only low to moderate yields of product. cCatalyst was reused two times (1-3 catalytic runs).5 mmol). and salicylaldehyde 2a (2. 5). entry 6). Furthermore.

The solution was cooled in an ice bath. Experimental To prepare catalyst. Then.47 In a 25-mL round bottom flask. it is evident from proposed mechanism that the reagents undergo several transformations without isolation of intermediates (one-pot approach).Novel Synthesis of 3-Phenyl-chromen-4-ones Using N-Heterocyclic Carbene Bull. a mixture of phenacyl bromide 1 (2. mild reaction conditions. The regenerated catalyst again reacts with intermediate 10 to initiate the catalytic cycle B. 0. it acts as nucleophile).5 mmol.6 mmol) was dissolved in 0.40 mL of 3 M NaOH (1. short reaction time and catalyst economy with minimal environmental impact are notable features of this procedure. 11 undergoes intramolecular nucleophilic addition (cyclization) followed by eventual regeneration of catalyst to give 13. followed by intramolecular nucleophilic substitution to give intermediate 9. Cycle A involves nucleophilic attack of thiamine (thiazolium ion) to carbonyl carbon of phenacyl bromide 1. Soc. Intermediate 13 then undergoes dehydration to give the desired product 3. No. then added 0.64 mL of water and added 2. 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. 34. 0. salicylaldehyde 2 (2. 2013. the mode of action of catalyst is same (i. Therefore.45 This intermediate 9 reacts with salicylaldehyde 2 to give 10 with regeneration of catalyst.28. it is an environmentally benign alternative to the existing conventional methods.6 mmol. tion as shown in Scheme 3.5 mmol. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1). Though the two catalytic cycles seem different (cycle B involves cyclization). Plausible mechanistic pathway. A and B. Vol. 4 1073 Scheme 3. It is a domino catalysis type scheme involving two catalytic cycles. Conclusion In summary. The operational simplicity. 0. Hence. the initiation of cycle B results in the phenomenon of reversal of polarity/umpolung at aldehydic carbon to give 11.30. The entire synthesis was carried out under varying experimental conditions including amount of catalyst and range of solvents in order to achieve optimum reaction condition.e. the fundamental mechanism is same in both the cycles (domino catalysis). The organic layer was dried over anhydrous Na2SO4 and the solvent was .21 g of thiamine hydrochloride (0.2 mmol) dropwise with stirring in a manner such that the temperature remained below 20 oC.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) . Hence.5 g in case of 1a) and thiamine (0..46 Following this. Korean Chem. we have developed an efficient and convenient 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.4 mL of 95% ethanol (water : 95% ethanol = ~1:4). The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL).

1. J = 7. 1H).28 (d. J = 7. 6. 126. 70.14. 123. 2H). 155. O.5. 7. 126. 6.86. 5. 67.27 (d. d.17 (s. 125. 1H).74. 125. 7-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-one (Formononetin) (3g). 7.61. 1. O. 2H). 124.19. 7.70 Hz.05. 2H).62 Hz. 2H). 7. 7. J = 1. J = 8. 3.87. The melting points were determined on a MAC.41. 1H-NMR (400 MHz.78 (d. 56.92 (s. 75. Found: C. Hz. H. 1H). 124.97.2. 153. 135. Found: C. H. J = 7.67 Priya Mishra et al. 4. 116. 7.0. 13C NMR (100 MHz. Vol.80. 101. 1.41 (t. 2. 135.31.04.72 Hz.21.83 (d.14. H.52 Hz.46. 128.65. 126. 1. 13C NMR (100 MHz. J = 7. J = 7. Calc. for C15H10O2. 1H). H. 7. 153.14. 123. EIMS (m/z): 252 (M+). DMSO-d6) δc 175. 7-Hydroxy-3-phenyl-chromen-4-one (3d).9.63.45.0. for C15H10O2. for C15H10O2. 2. 98.56 Hz.60 Hz.5. 123.60 Hz. 1H). 5.05 Hz.45 (s. 23. 8. 3.03. 4. 1H-NMR (400 MHz. 6. 1H).75 (d d. 7. Pale yellow crystal. for C15H10O2. 1H). 2H). 1H).69.55.04. 9. 127.04. 1H). Calc. 153.62. 7. DMSO-d6) δH 8. 160. 2H). 25.1. 7. 1H).analyzer.51. 113.28 (t. 2H).5.05 (d. 71. C. 1H). 1H). 99. 7.80 (s. DMSO-d6) δH 9. The resulting product isoflavone 3 was further purified either by recrystallization or by column chromatography (Ethyl acetate:Hexane. 7. Found: C. 111. 4. 54.5. 25.1.88 (d. Anal.45 Hz.4. 3. 154. 1H). 124.71 Hz. 1H).6. 123.94. 9. Found: C. 2H). 130.56.89. 72. O.64. 8. J = 7. 7.90 (d. O. 9. 1H).5.6. mp 320-321 oC. 7. 130. 4.82 (m. 1H). Calc. 19.61. Found: C. No. EIMS (m/z): 254 (M+). H.2. O. 1H-NMR (400 MHz.4.78 (s.40 (d d.40 Hz.03. Found: C. 1H).60. 7. 154. 6.3. multiplet. Anal. 7. Anal.33 (t. DIGITAL MELTING POINT APPARATUS and were uncorrected.50 Hz. H. O. 3. Anal. 131. J = 7. 132.7. 71. 157. Calc.9. O.03.71. triplet. 125. 6. mp 220-222 oC. 3-(4-Methoxy-phenyl)-chromen-4-one (3b). J = 8. C.95 Hz. 7. 4.92. mp 195-198 oC.37 (d. J = 7.51 (s. DMSO-d6) δH 9.1. J = 7. EIMS (m/z): 282 (M+). 3. J = 7.86.48 Hz. 7-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (Daidzin) (3f).01. 8. H. 1H). DMSO-d6) δH 9.53.03. 4. 6.1.80 (d. Calc. 7. Anal. 13C NMR (100 MHz. 1H). 6. 1H). The chemical shifts are expressed in ppm: s.79.96.60 Hz. 23. 153. 23. mp 162-164 oC. 6. 8. 1H). 125.21.56.36 (m. 109. J = 7. 126. O. O. 1. 6.64. O. 6. J = 7. J = 7. EIMS (m/z): 268 (M+).51.95 (s.82. for C15H10O2. 1H). Calc. mp 210-213 oC. for C15H10O2.14. White solid.50 (d d. J = 8. 1H (400 MHz) and 13C (100 MHz) spectra were recorded on a Bruker Avance II 400 spectrometer. 2H). 53. 1H-NMR (400 MHz. 150.00 (d d.81. 116. 1H). singlet. 76.31 (s.99 (d d. 81.19.90 (s.85 (d. 158. 119. 154.24. J = 8.7 Hz. 7. 1H).11. 19.57 Hz. 22.60. 1H). 105.06. J = 7. The products were purified either by recrystallization or by column chromatography.49 Hz. 113. O. 116. 2H). H. 34. J = 7.31. 1H).75 (d d. 1H). 1H).1. Anal. 7. 1H). 163. 1. J = 8.56.95. H. 127. 155.48 (d d. 7. J = 7. 2H). 3H).82.1.5.24. 7.0. J = 8. for C15H10O2. 4. 123. 25.20 Hz. 110. C. 1H). C. Found: C.65 (s.43 Hz.64 (s. 81. 3H).37.3. 8.71.04.59 Hz.90 (s. Korean Chem. 100. J = 7.5.26 (s. 2H).92 (s.5. 1H). 3H).28 (t. 3H).35 (d. 13C NMR (100 MHz. Soc. DMSOd6) δH 9. O.25.96.80 (s. 3-(4-Hydroxy-phenyl)-7-methoxy-chromen-4-one (3h). for C15H10O2.17. 3-(4-Nitro-phenyl)-chromen-4-one (3c). J = 7. 112. 25. 158. 1H).00 Hz.11. 1H). J = 7. 55. 1H-NMR (400 MHz. 1H). 1. for C15H10O2. 75.03. J = 8.39.32 (t.25 (t.84 (d. J = 7.1. 3H). O.89.63.21 (t.2. N.25. 121. 13C NMR (100 MHz. 19. 115.63. 2H).99. C.25. mp 150-155 oC. EIMS (m/z): 238 (M+). N. DMSO-d6) δc 175.2.1H). J = 8. 1H).27 (s.1. 76.82. 1H).64 (s.96.00 Hz. 124. 157. 7. J = 8.65. Anal. 150. DMSO-d6) δc 172. 4.35 .35 (s. 128. 157.18. 153. DMSO-d6) δH 8. 13C NMR (100 MHz. 7-Methoxy-3-(4-methoxy-phenyl)-chromen-4-one (3i).80 Hz. 149.30. J = 7. 1:4 v/v). 3H). 157.67 Hz.05. 114.2. EIMS (m/z): 222 (M+). 156. 1. 7. 125. H. 5-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (3k).03. 6.50 Hz.71 Hz.4. 7. 4.86.30 (s. Anal. DMSO-d6) δH 8.59 Hz. 7.68 Hz. 1H). 152.0. White solid. 7.6.47 Hz. 71.1. 3-Phenyl-chromen-4-one (3a).40.94 (s. 118.85.58 Hz. H.40 Hz. 4. 115. 116. O. 126. Found: C. 1H). 132. 165.86. Found: C. 153. 54.22 (d d. H.77 Hz. 3. 7. The starting materials used were purchased from Aldrich Chemical Company and were used without any further purification.40 (d.85 (d d. 3. 122.2. 5. mp 157-158 oC. 1H). J = 7.80 (d d. 3H). 3. 3.33. 111. 122. 153.53 Hz.67.62 Hz. 1H). 20. 126.79 Hz. 22. 151. EIMS (m/z): 252 (M+). 1H-NMR (400 MHz. 19. 5. 7. 126. Calc. 20.61 Hz.14. 7. 115.3. H.9. J = 7.69. DMSO-d6) δc 171. 14.74.03. C. mp 160-162 oC. 67. 70. 2H).63 Hz. Calc. Colourless needles.11.1. 70. 127. 1. 115.03. 1. DMSO-d6) δc 170. 4 removed under reduced pressure. 127.81 Hz.1. Found: C. 1H). 143. mp 168-170 oC.25.42 Hz. 1H).73 (s. 1. 13C NMR (100 MHz.20 (t. J = 7. 148.71.17.4.04. 119. 1H).69 Hz.00 Hz. 153.96 (s. 1H).79. 72. 3. H.62 (s.1.93.90 (s.36 (d.15. C. J = 8. 71. Orange solid. J = 8. δH 9. 123. DMSO-d6) δc 172.9. 1H).86.66 Hz. 13CNMR and mass spectral data. 120. 1H). 8. 1H). J = 7. 157. 124. H. DMSO-d6).28 (s. 4. 6.05 Hz. 7.07.81. 123.33.28 (t. 3H).83 Hz. 76. 55. 4. t. mp 255-257 oC. 23.05. 7. White solid. 98.86 (d.3.3. 6. 6.11. 70. 6. 1HNMR (400 MHz.03.83 (s. 13C NMR (100 MHz.1074 Bull. 125. DMSO-d6) δc 175. White solid. J = 7.67 (s. 7-Methoxy-3-phenyl-chromen-4-one (3e).15. J = 7. m.40 (t. 127.5. DMSO-d6) δH 8.52 (s. 13C NMR (100 MHz.48 Hz. J = 7. 126. EIMS (m/z): 267 (M+). Pale yellow crystal.52 Hz. 132.0. 127. 117.86. 6-Hydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (3j).53 Hz. 1H).1. H.51 Hz. 6.6.96. 8.88 (d. 8. 3H). O.12 Hz. calc. 3.94.02 (d d.95. 23. J = 7. 124.2.65 (d.57. 1H-NMR (400 Hz. 123. O.46 Hz. 130.01.55. DMSOd6) δH 9. Elemental analyses were performed using a Vario EL III CHN-O. 1H).0. 112.75 Hz. C. EIMS (m/z): 268 (M+).20. DMSO-d6) δH 8. Yellow crystal. 112.27 (s.6. All compounds were characterized by their mp and 1HNMR. 122. White solid.25.52 (d d.31.3. 7. Calc.90 (d.65 (t. 117. Anal. 23. 2H). DMSO-d6) δc 175. 76. 1. O. O.25. 1H).42. EIMS (m/z): 254 (M+).8. J = 7.57.17. 1H-NMR (400 MHz.80 (s.18. 8.1. 117. 2H). 7. mp 218-220 oC.50 (d d. 1. O. 3. J = 7. 1H). 14. 1H-NMR (400 MHz. Anal.56 Hz. 161.97.40. O. 127. 162.80 (m. 6.85 Hz. 2H). doublet.6. H. 128.90 Hz. J = 8.54. 2013. H.23. H.32 (s.84 (d. 8.7. 161. 124. H. 1H-NMR (400 MHz.56.83.59 Hz.33. DMSO-d6) δc 175. C. 13C NMR (100 MHz.82. 1H).8.60 Hz.75 (d d.20. DMSO-d6) δc 169. 126.00. C. for C15H10O2.24. 157. 135.69 (s. Crystalline solid.28 Hz.

38. J. H.. Synlett. Ed. Andreeva.33. 1991. 950.6.. 9696. H. S. A. W. H. Pohl. Med. H. H. 60. Schmidt. Calc. G. Med. Yokosawa.83.88 (d. (f) Hajela. S. E. J. Nirsche.67. Statti. 6.(Chem.92. 23. 1966. Grabowski.. 123. Chern. 834. 67. Rep. 2008. S.97. J. N. Maurya. Anal. 2001. 108. Xiao. Sprenger. 6. Nogradi. Postnikova. 38(3). 63. 3. B: Enzym. C.62 Hz. mp 211-212 oC. 4. H. S. Pharm.82. Raffauf. 20. A. Stucki. DMSO-d6) δc 175..81 (d.2. 2010. New Delhi for the award of Senior Research Fellowship (SRF). 110. L. Mikuni. Bang..72 Hz. J. R. McGown.71 Hz. C.. M.... J.. Nat.. Qian. 1993. 184. 157. K. S.4. 695.. 661. P. Soc. H.21. 1H). Yao. 1997. Merlini. Houghton. 3071. Org. Chem. H. 3. Pure Appl.. A. Y. L. Med. S. P. 6. for C15H10O2. Padwa. S.62 Hz. 2003. Lebedava. Chem. 125. 19. 1H). A. T. A. G. 55. R. S.. Biophys. K. 6.. Exp. Suzuki.5. 1951.8.. D. 1H).50 Hz.. 14. H. P. Res. J. And the publication of this paper was supported by the Korean Chemical Society.. Chem. R.62.. (b) Farkas. Pohl.. Z.1. 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Chem.. Off-white powder. 15. P. K. 3H). 6. Lingen. G. Baragwanath. E.-S. Chem. 110. Soc. J. 70.7-Dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (Genistein) (3m). T. F. 25.14. M.. V. Namgoong... Breslow. 3. 1H). Chem. M. Jpn. J = 7.00 (d d. Chem. 8. S. 3. A.20 (s. Tetrahedron Letters 1977. 1311. 1990. Sawhney. F. 11. 1979. 7.. 1976. O. M.1. EIMS (m/z): 270 (M+). H. 5.1. T. Wang.56. A.03.6. S. R. R. Q. Pharm. 42. Chem. Ozimina. W. H. H. 233. J = 8. M. Lee.4. 80. A. 1987. 1550. 12084. O.57 Hz. K. Science 1975.. 13C NMR (100 MHz.8. 102. A. A. Perkin Trans I 1991. P. J. 7. 3707. M. Angew Chem.04. K. S. H.. Miyaura.Novel Synthesis of 3-Phenyl-chromen-4-ones Using N-Heterocyclic Carbene Bull. Eur. 7. Pharm. 136. Med. 2H). 7. Chinen. Soc. 101.. Chem. 2. D. *three nearly overlapped singlets. Prod.67 Hz.77 (s. 479. J. 10.9. 133. A. 2H). Med. (b) Jain. 1943. Ju. Tetrahedron: Asymmetry 2003.17. 1. R. 10. Edwards. 49. Zhao. 3. Bioorg. Am.51. Demir.. U. 1986. Mol.. 157. M. Biochem. 407. Tillyer. A. J. S. S. 158. I.. 2H). S.. 229. S.. Siva Prasad. A.. J = 8. Renzi. O. Agric... 133. (a) Stetter. B. 5-Hydroxy-3-(4-methoxy-phenyl)-chromen-4-one (3l).5. 119. Siegert..78. 13C NMR (100 MHz. K. for C15H10O2. N. C. C.66 (s. 124. Org. J = 7. 126. O. Soc. Am. 32(2). Chem. 125. 127. Synthesis 1995. A. Jpn. Bhargavan. Bioorg.. (b) Peterson. Abstr. W.. Allakhverdi. Commun.. Neuklis.5. D. Tetrahedron Lett. Yang. 2002. 1H-NMR (400 MHz. (b) Dünkelmann.. Anal.57 Hz. Frantz.83. Maurya. C. The authors are also greatful to CSIR and UGC. Singh. A. Soheili. H. Le Quesne.53.1H). Angew. F. M. Lee. (a) Miksicek. M. Kinoshita.. W. J. Found: C. O. 1993. 88. 154.. M. R. W.25 (s.. 21. O.88.. Chem. Crit. Acknowledgments. Found: C. Arch. H.. 2003.. J.. Vashchenko. C. 8.8. S.. P. 3. 9. J = 8. Am. Cho. 18. 30. 61.. 16..61 Hz..Verykokidou..8. 4 (d. (e) Krishnamurty.41. 593. K. Lee. V. 76. 14. 162. 23. Chem. C. 153. DMSO-d6) δc 175.. Calc.. A.. Soc.. 44.63.. Jung.5.. R. Bull. 296. F. Chandigarh for providing micro analysis and spectra. 1075 N. 29. J = 7. 12. 96. Proc. DMSO-d6) δc 183. 158. Rawat. Singh.66. Venkataraman. 128. C. Ding. 168. Biol. (c) Kagd. DMSO-d6) δH 9..25. 78. I. P. 6. M. J. Am. Kapil. (d) Arnold. 8432.. 1232. DMSO-d6) δH 9. 90. Hamelmann. 26. 6. 120. J = 8. D. Morrow. 1H).49 Hz.89. 639. 114. R.86. 124. 561. 3H). 2002.60. Jensen.20 (s*. 1..-B. 16.. R. Sahai. 3008 (d) Paquette. H. 2006. A. 2013. 1H). E. X. Eur. 80. 106. Pure Appl. Calc. EIMS (m/z): 268 (M+). 3H). 6. Tundis. 5.. T.. 2H). Znd. M. Rackelmann. Res. S. Read de Alaniz. H. 326. Rovis. 2001.-L. H. A. K. E.. Lett. H.9. J. 1706. A. 8... 188. Zentralbl. A. 769.19 (t. 46. Tietze. Jung. Potten. 22.. 1988. P. Dang. 6. Chem. Yamane. R.. 208(l).68 Hz.. B.75.1. 607.69 Hz. 3005.64. (a) Jordan. 305 (c) Hoshino. Found: C..03. Adachi.92. Bioorg. A. 1969. Kim. 13 C NMR (100 MHz. Murry.. Baziou. 1H). J = 7. 2002.. 20. (a) Noonan. Menichini. Caporale. 27. Breimaier. 103. 162. R. 1967.. 34. 7. H. Med. S. Lee. 1385. T. Y.. H. 3036. Hargreaves. Acta 1998.. Bull. 1.28-9. O. Prod.. Y.81. 125. L. Mikrobiol. Chang. Dokawa. 8.35 (d. 1967. M. 19. (a) Cigannek. Jung. (a) Pelter. 1H). O. P.89. (b) Stetter. 3719. Int. J. (c) Hachisu. 179(I).. J. H. Chem. 3. C. 3759. C.1.43 Hz. 2H). 111. 2004.35 (s*. Tetrahedron Letters 1962. (a) Sekizaki. Food. J. 4003. J = 7. O.86.1H). Hadfield. (c) Spernger. G. 2007. DMSO-d6) δH 9. 25.. 4.80 (d d. 7. EIMS (m/z): 284 (M+). Y. 117. 2011. Murthy. 13C NMR (100 MHz. 5. C. 45. Pharm.33. 158. 123. Calc. 123. J = 7.. T. Cherevatyi.. Kim. M. W. React. M.71. 151. 16. 113. S.56. Wang.57.05.1. O. K. Booth.-W. J. 610. We sincerely thank SAIF. Int. Ugai. 16. 1976.. Tan powder. 1H).. J. J. S. Synthesis 1976. Med. 3827. H. M. Anal. L. H. (b) Kerr.. 1. W. A. Angm. Chem.1. 17.7-Dihydroxy-3-(4-methoxy-phenyl)-chromen-4-one (Biochanin A) (3n).. 18.54 (s... 1066.. 4. 71.8. (b) Schoerken. Med.-J. G. (c) Orlandi. Ryu. F. Annunziara. Moersch. Phytother. Loukis.53 Hz. J. Varma. J. 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