Efficient syntheses of new polyhydroxylated 2,3-diaryl-9H-xanthen-9-ones

FULL PAPER

DOI: 10.1002/ejoc.200900026

Efficient Syntheses of New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

Clementina M. M. Santos,^[a,b]Artur M. S. Silva,*^[b]and José A. S. Cavaleiro^[b]

Keywords: Xanthones / Alcohols / Oxygen heterocycles / Heck reaction / NMR spectroscopy

A large number of hydroxylated 2,3-diaryl-9H-xanthen-9-

ones have been synthesised by two different approaches,

starting either from 3-bromo-2-methyl-4H-chromen-4-one or

from (E)-3-bromo-2-styryl-4H-chromen-4-ones. The former

method involves Heck reactions between 3-bromo-2-methyl-

bromo-2-styryl-4H-chromen-4-ones and styrenes, followed

by electrocyclisation and oxidation processes. The 2,3-diaryl-

3,4-dihydro-9H-xanthene-9-one intermediates were also iso-

lated under these conditions, and so when 5-methoxy-2-sty-

ryl-4H-chromen-4-ones were used as starting materials the

4H-chromen-4-one and styrenes, leading to (E)-2-methyl-3- 1-hydroxy-6,7-diaryl-9H-xanthene-9-ones were also ob-

styryl-4H-chromen-4-ones; these condensed with benzalde- served. The second method is a general one, because it al-

hyde to give (E,E)-2,3-distyryl-4H-chromen-4-ones, which

led to the desired 2,3-diaryl-9H-xanthen-9-ones under reflux

in 1,2,4-trichlorobenzene. 3-Bromo-2-styryl-4H-chromen-4-

ones were obtained either by aldol condensations between

3-bromo-2-methyl-4H-chromen-4-one and benzaldehydes,

or through Baker–Venkataraman rearrangements of 2-ace-

tylphenyl cinnamates, followed by one-pot bromination/

cyclisation with phenyltrimethylammonium tribromide. The

2,3-diaryl-9H-xanthene-9-ones were obtained in one-pot

transformations involving Heck reactions between (E)-3-

lowed the synthesis of a great number of 2,3-diaryl-9H-

xanthen-9-ones with several substitution patterns, whereas

the first one is limited to certain derivatives. The last step in

the synthesis of hydroxylated 2,3-diaryl-9H-xanthen-9-ones

was the cleavage of the hydroxy protecting groups with bo-

ron tribromide. The structures and stereochemistry of all new

compounds were established by NMR studies.

Germany, 2009)

ies of phenolic compounds have revealed that features con-

ducive to high antioxidant activity are the presence of hy-

droxy groups at certain positions on the skeleton, a catechol

group being the most prominent moiety.^[20,21]In view of

these considerations, here we report two main routes for

the synthesis of polyhydroxylated 2,3-diaryl-9H-xanthen-9-

ones.

There are various known methods for the synthesis of

9H-xanthen-9-ones.^[22]The classic ones involve the bonding

of two benzene rings through a pyran unit. The most com-

monly reported are Friedel–Crafts acylations of phenolic

derivatives with benzoyl chlorides and Ullmann condensa-

tion between sodium phenolates and ortho-halo-substituted

benzoic acids for the synthesis of diaryl ethers, with both

methods being followed by cyclisations of these compounds

to form the heterocyclic rings. The literature also reports

direct formation of the 9H-xanthen-9-one nucleus through

a diaryl ester pyrolysis process or by photo-Fries or Smiles

rearrangements of these intermediates, accompanied by

ring closure. These classical methods require some drastic

conditions, give poor yields because of the formation of sev-

eral by-products and only allow the presence of certain sub-

stituents in certain positions on the 9H-xanthen-9-one

core.^[22–24]

Introduction

Xanthones constitute one of the major classes of natu-

rally occurring oxygen-containing heterocyclic compounds

containing dibenzo-γ-pyrone rings.^[1]They occur in two

major plant families, Guttiferae and Gentianaceae, and also

in some families of fungi and lichens.^[2,3]Natural derivatives

can be hydroxylated, methoxylated or prenylated, among

other possibilities; the parent compound xanthone itself is

not known as a natural product.^[3,4]The presence of aryl

groups on the xanthone core has only been reported for a

few synthetic derivatives, and as far as we know the litera-

ture had never presented the synthesis of xanthones featur-

ing 2,3-diaryl moieties before our work.^[5,6]

Over the last decades these substances have been exten-

sively studied not only because they participate in several

biological functions but also as a consequence of their re-

markable antifungal,^[7–9]anti-inflammatory,^[10,11]antima-

larial^[12–14]and antitumour activities,^[15,16]and even as

promising antioxidant agents.^[17–19]Structure–activity stud-

[a] Department of Vegetal Production and Technology, Escola

Superior Agrária de Bragança,

5301-855 Bragança, Portugal

Fax: +351-273-325405

E-mail: clems@ipb.pt

[b] Department of Chemistry & QOPNA, University of Aveiro,

3810-193 Aveiro, Portugal

Modifications of the classical methods and several other

less traditional approaches to construction of the 9H-

xanthen-9-one framework have been widely described, but

Fax: +351-234-370084

E-mail: artur.silva@ua.pt

2642

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

Scheme 1. Synthesis of 2,3-diaryl-9H-xanthen-9-ones 5a–f.

none of them allows the synthesis of our target compounds, chromen-4-ones 3a and 3b and styrenes 4a–c in the presence

the 2,3-diaryl-9H-xanthen-9-ones.^[22]In this context, we of tetrakis(triphenylphosphane)palladium(0) as catalyst, di-

have developed two methods for the synthesis of new poly- rectly giving the 9H-xanthen-9-ones 5a–f (see Exp. Section,

hydroxylated 2,3-diaryl-9H-xanthen-9-ones, starting from Table 2). Under these conditions it was also possible in each

3-bromo-2-methyl-4H-chromen-4-one (1, Scheme 1) and the case to isolate a minor compound with lower R_fvalue, cor-

(E)-3-bromo-2-styryl-4H-chromen-4-ones 3a–k (Scheme 2).

responding to the 2,3-diaryl-3,4-dihydro-9H-xanthen-9-one

intermediates 6a–f.

An alternative method for the synthesis of 2,3-diaryl-9H-

xanthen-9-ones started with Heck reactions between 3-

bromo-2-methyl-4H-chromen-4-one (1) and styrenes 4a–c

(Scheme 1). Several attempts to optimise the coupling reac-

tion conditions were made, and the best results for the syn-

thesis of the (E)-2-methyl-3-styryl-4H-chromen-4-ones 7a–

c were achieved with 1 molar equivalent of base, 0.1 molar

equivalent of phosphane and 5 molar equivalents of sty-

renes 4a–c over 9 h at 160 °C. Unlike in the coupling reac-

tion described above, in which the best results were achieved

with tetrakis(triphenylphosphane)palladium(0), here the

best yields were obtained in the presence of palladium chlo-

ride as catalyst (Table 1).

Results and Discussion

Syntheses

Our first approach to the synthesis of 2,3-diaryl-9H-

xanthen-9-ones involved the use of the functionalised 3-

bromo-2-methyl-4H-chromen-4-one (1), which was pre-

pared from 2Ј-hydroxyacetophenone in a three-step se-

quence and in a good overall yield.^[25–26]Two methods to

obtain the 2,3-diaryl-9H-xanthen-9-ones 5a–f were devel-

oped (Scheme 1). In one of these, the (E)-3-bromo-2-styryl-

4H-chromen-4-ones 3a–c were prepared through base-cata-

lysed aldol reactions between 4H-chromen-4-one 1 and

benzaldehydes 2a–c in methanolic solutions. The best re-

The (E,E)-2,3-distyryl-4H-chromen-4-ones 8a–c were

sults were achieved when 4 molar equivalents of base and prepared through base-catalysed aldol condensations be-

reaction times of 48 h were used. Even after several tween the (E)-2-methyl-3-styryl-4H-chromen-4-ones 7a–c

attempts, the yields of (E)-3Ј,4Ј-dibenzyloxy-3-bromo-2-sty- and benzaldehyde (2a) in the presence of 4 molar equiva-

ryl-4H-chromen-4-one (3c) never exceeded 6% and its isola- lents of base over 48 h at room temperature. Condensations

tion and characterisation was not possible, due to its degra- between the (E)-2-methyl-3-styryl-4H-chromen-4-ones 7a–c

dation in chloroform solution.^[25]The next step consisted and the benzaldehydes 2b and 2c were unsuccessful, proba-

of Heck reactions between the (E)-3-bromo-2-styryl-4H- bly due to poor reactivity of benzyloxybenzaldehydes 2b

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2643

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

Table 1. Yields for the formation of (E)-2-methyl-3-styryl-4H- major one with the highest R_fvalue corresponding to the

chromen-4-ones 7a–c through Heck reactions between 3-bromo-2-

methyl-4H-chromen-4-one (1) and styrenes 4a–c.

desired 2,3-diphenyl-9H-xanthen-9-one 5a, together with

two other minor compounds. Their NMR spectra showed

Catalyst [equiv.]

% Yield 7a

% Yield 7b

% Yield 7c

that the minor product with high R_fwas 2,3-diphenyl-3,4-

dihydro-9H-xanthen-9-one (6a) and the other, with a lower

R_f, was 2,3-diphenyl-1,2-dihydro-9H-xanthen-9-one (9a).

After 18 h, however, only the desired 2,3-diphenyl-9H-

xanthen-9-one (5a) was obtained.

Pd(OAc)₂(0.05)

Pd(PPh₃)₄(0.05)

PdCl₂(0.05)

46

48

28

43

49

17

30

52

In view of the lack of reactivity in some steps in the two

previously described methods, we developed a third and

more general method for the synthesis of 2,3-diaryl-9H-

xanthen-9-ones, starting from the 2-acetylphenyl cinna-

mates 10a–i (Scheme 2).^[27]The cinnamates 10a–i were ob-

and 2c. The 2,3-diaryl-9H-xanthen-9-ones 5a–c were then

obtained by heating the (E,E)-2,3-distyryl-4H-chromen-4-

ones 8a–c in 1,2,4-trichlorobenzene at reflux. In the case of

the unsubstituted 2,3-distyryl-4H-chromen-4-one 8a, TLC

analysis of the reaction medium after a reaction time of tained in good yields from reactions between acetophe-

12 h revealed the presence of three compounds, with the nones and cinnamic acid derivatives. Baker–Venkataraman

Scheme 2. Synthesis of 2,3-diaryl-9H-xanthen-9-ones 5a–c, 5g–s and 12n–s.

2644

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

rearrangements of 10a–i in the presence of potassium hy- Table 3. Best experimental conditions (T in all cases: reflux temp.)

for the synthesis of 2,3-diaryl-9H-xanthen-9-ones 5g–s, 2,3-diaryl-

droxide in DMSO gave the desired 5-aryl-3-hydroxy-1-(2-

3,4-dihydro-9H-xanthen-9-ones 6g–s and 1-hydroxy-6,7-diaryl-9H-

hydroxyaryl)penta-2,4-dien-1-ones 11a–i in good yields.^[28]

xanthen-9-ones 12n–s.

The key step in the synthesis of the (E)-3-bromo-2-styryl-

t

%

t

%

% Yield

4H-chromen-4-ones 3a and 3d–k involves treatment of

ketones 11a–i with phenyltrimethylammonium tribromide

(PTT) in THF at room temperature. The presence of this

reactant promotes a one-pot transformation, involving

ketone α-bromination^[29]followed by cyclisation to afford,

after careful column chromatographic purification, the 3-

bromo-2-styryl-4H-chromen-4-ones 3a and 3d–k.

An extensive optimisation study on Heck reactions be-

tween the (E)-3-bromo-2-styryl-4H-chromen-4-ones 3a and

3d–k and the styrenes 4a–c was carried out, with investiga-

tion of the amounts of base and styrene and the reaction

time and temperature. These reactions afforded the desired

2,3-diaryl-9H-xanthen-9-ones 5a–c and 5g–s, the 2,3-diaryl-

3,4-dihydro-9H-xanthen-9-one intermediates 6a–c and 6g–s

and also the 6,7-diaryl-1-hydroxy-9H-xanthen-9-ones 12n–

s, in the cases of compounds 3h–k, each bearing a 5-meth-

Yield Yield Yield

Yield Yield

[h]

5

6

12

[h]

5

6

12

g

h

i

j

k

l

m

n

o

p

q

r

9

3

6

9

6

9

6

60

62

28

62

80

70

47

58

24

22

50

43

42

11

–

3

–

17

–

10

–

37

3

6

3

6

9

3

6

3

6

3

49

46

21

41

46

55

33

47

16

22

43

31

21

43

10

4

13

21

6

21

12

43

5

17

13

46

–

12

2

1

11

2

34

5

1

–

s

Finally, to afford the desired polyhydroxylated 2,3-diaryl-

oxy group from which the methyl group was cleaved off 9H-xanthen-9-ones 13b–s it was necessary to cleave the ben-

during the reaction. The yields of each of these compounds zyl and methyl groups of the 2,3-diaryl-9H-xanthen-9-ones

changed according to the experimental conditions used (see 5b–s. Boron tribromide in dry dichloromethane was used as

Experimental Section, Table 2 and Table 3).

deprotecting agent for simultaneous cleavage of both pro-

Table 2. Best experimental conditions for the synthesis of the 2,3-diaryl-9H-xanthen-9-ones 5a–f and the 2,3-diaryl-3,4-dihydro-9H-

xanthen-9-ones 6a–f.

Time

[h]

Temperature

% Yield 5Ͼ

% Yield 6

Time

[h]

Temperature

% Yield 5

% Yield 6

[°C]

a

b

c

d

e

f

9

3

12

6

12

160^[a]

160

reflux

reflux^[a]

reflux

56

66

45

51

66

39

–

14

–

9

3

12

3

160

54

58

44

46

25

36

9

–

6

11

27

28

160^[a]

reflux

27

[a] Et₃N (4 equiv.).

Scheme 3. Cleavage of the hydroxy protecting groups.

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2645

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

Figure 1. Structures and numbering system used for (E)-3-bromo-2-styryl-4H-chromen-4-ones 3a–c, (E)-2-methyl-3-styryl-4H-chromen-

4-ones 7a–c, (E,E)-2,3-distyryl-4H-chromen-4-ones 8a–c, 9H-xanthen-9-ones 5a–f, 5n–s, 12n–s and 13n–s and 5-aryl-3-hydroxy-1-(2-hy-

droxyphenyl)penta-2,4-dien-1-ones 11a–i. (We applied the recommended IUPAC rules to establish the names of all compounds, but

preferred the numbering systems indicated in Figure 1 and retained this atom numbering of each compound for reasons of better compara-

bility of NMR data. For example, according to IUPAC nomenclature the 9H-xanthen-9-ones 5a–f and 5n–s, 12n–s and 13n–s must have

different numbering, but we kept the same numbering for consistancy of NMR signal assignments).

1

tecting groups.^[30,31]The polyhydroxy-2,3-diaryl-9H-

The H NMR spectra of the (E)-3-bromo-2-styryl-4H-

xanthen-9-ones 13b–s were obtained in moderate to good chromen-4-ones 3a–k each revealed the presence of two

yields (Scheme 3, Figure 1).

doublets, corresponding to the vinylic protons α-H and β-

H [δ = 7.20–7.46 and 7.58–7.73 ppm, respectively] in a trans

configuration (J ≈ 16.0 Hz). The high-frequency values as-

signed to the resonances of β-H and C-β (δ = 138.1–

139.6 ppm) relative to the resonance of α-H and C-α (δ =

116.9–119.3 ppm) are due to the mesomeric deshielding ef-

fect of the carbonyl group. HMBC spectra allowed the as-

signment of the quaternary carbons of the chromone moi-

ety: C-2 and C-9 at δ = 156.1–158.8 and 154.8–158.4 ppm,

respectively, C-3 at δ = 108.9–116.9 ppm and C-10 at δ =

107.5–122.1 ppm.

Nuclear Magnetic Resonance Spectroscopy

1

The most important features in the H NMR spectra of

the

5-aryl-3-hydroxy-1-(2-hydroxyaryl)penta-2,4-dien-1-

ones 11a–i are, in each case: i) the singlets at δ = 6.17–6.80

and 12.28–13.63 ppm, corresponding to 2-H and 2Ј-OH,

respectively, and ii) a doublet at δ = 14.51–15.01 ppm with

J ≈ 1 Hz, due to long-range coupling with the 4-H proton,

corresponding to the 3-hydroxy group. The high-frequency

values of the last two signals are due to the deshielding

An important feature in the ¹H NMR spectra of the (E)-

effect of the hydrogen bonds of the hydroxy protons with a 2-methyl-3-styryl-4H-chromen-4-ones 7a–c is the presence

carbonyl group. NOESY correlations between the signal of in each case of a singlet corresponding to the 2-CH₃pro-

2-H and those of 4-H and 6Ј-H (for 11a–e), and of 4-H and tons at δ = 2.61–2.62 ppm, and doublets corresponding to

5-H with 2ЈЈ,6ЈЈ-H, together with the coupling constant of the olefinic protons α-H (δ = 6.83–6.97 ppm) and β-H (δ =

J_H4,H5= 15–16 Hz indicate that the compounds of this type 7.59–7.71 ppm) in a trans configuration (J = 16.3 Hz). The

have planar (Z)-s-(Z)-(E) configurations (Figure 2).

difference in the chemical shifts is due to the deshielding

Figure 2. Main NOE cross peaks found in the NOESY spectra of the 2,3-diaryl-3,4-dihydro-9H-xanthen-9-ones 6a–s, the (E,E)-2,3-

distyryl-4H-chromen-4-ones 8a–c and the 5-aryl-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-ones 11a–i.

2646

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

Figure 3. Important connectivities found in the HMBC spectra of the 2,3-diaryl-9H-xanthen-9-ones 5a–s, 12n–s and 13b–s, the 2,3-diaryl-

3,4-dihydro-9H-xanthen-9-ones 6a–s and the (E,E)-2,3-distyryl-4H-chromen-4-ones 8a–c.

effect of the chromone moiety, β-H being the more deshi- xanthen-9-ones 5a–s, 12n–s and 13b–s, allowing the assign-

elded. NOESY correlations between the protons of the ment of the quaternary carbons of the xanthone cores. The

methyl group and the two protons α-H and β-H, indicate main connectivities are: i) 4-H and 2Ј,6Ј-H with C-2, ii) 1-

free rotation around the C-3 and C-α bonds. The ¹³C NMR H and 2ЈЈ,6ЈЈ-H with C-3, iii) 1-H and 4-H with C-4a, iv) 5-

spectra of the (E)-2-methyl-3-styryl-4H-chromen-4-ones H and 6-H with C-4b, v) 5-H and 7-H with C-8a, and vi) 4-

7a–c each present the characteristic signals corresponding H with carbon C-9a (Figure 3).

1

to the 2-methyl carbon at δ = 19.3–19.4 ppm, to C-2 at δ =

The H NMR spectra of the 2,3-diaryl-3,4-dihydro-9H-

163.3–163.8 ppm and to the carbonyl carbon at δ = 176.9– xanthen-9-ones 6a–s in each case revealed the presence of

177.0 ppm. the aliphatic protons H-3 and H-4. The signal correspond-

The NMR spectra of the (E,E)-2,3-distyryl-4H-chromen- ing to 3-H appears as a doublet or a double doublet, at δ

4-ones 8a–c are not easy to interpret because of the sym- = 4.22–4.31 ppm and at a higher-frequency value than that

metry of the molecules and the fact that all the signals are of H-4. From the coupling constants, the stereochemistry

in the aromatic region, except for the signals corresponding of 4_cis-H (J = 8.3–9.1 Hz, δ = 3.57–3.67 ppm) and 4_trans-H

to 5-H, which each appear as a double doublet at the high- (J = 1.3–1.6 Hz, δ = 2.89–3.01 ppm) is related to 3-H. An-

1

est frequency value (δ = 8.22–8.25 ppm). The assignment of other main feature in each H NMR spectrum is the pres-

the two AB spin-systems, due in each case to the resonances ence, in the aromatic region, of a singlet at δ = 7.44–

of α-H (δ = 7.37–7.42 ppm), β-H (δ = 7.67–7.71 ppm), αЈ- 7.56 ppm corresponding to 1-H. The correlations found in

H (δ = 7.11–7.21 ppm) and βЈ-H (δ = 7.27–7.43 ppm), was the HMBC spectrum between this singlet (1-H) and the sig-

made on the basis of the connectivities found in the HMBC nal of the carbonyl carbon and also between the signal of

spectra. The correlation observed in these spectra between 3-H with those of carbons C-2ЈЈ,6ЈЈ, supports the presence

the signal of the carbonyl carbon and the doublet at δ = of the 3,4-dihydro-9H-xanthen-9-one moiety (Figure 3).

7.11–7.21 ppm identifies αЈ-H (Figure 3). The coupling con- This structure was also confirmed by the correlations found

stants of the vinylic systems (J ≈ 16 Hz) indicate their trans in the NOESY spectrum, mainly those indicating close

configurations, whereas the NOE cross peaks between the proximity of 1-H to 2Ј,6Ј-H, of 3-H to 2Ј,6Ј-H and 2ЈЈ6ЈЈ-

signals of α-H and αЈ-H, as well as those of α-H and 2Ј,6Ј-H H and of 4_cis-H and 4_trans-H to 2ЈЈ,6ЈЈ-H (Figure 3).

and also of αЈ-H and 2ЈЈ,6ЈЈ-H, support the conformations

presented in Figure 2 for compounds 8a–c.

1

In the H NMR spectra of all the synthesised 2,3-diaryl-

Conclusions

9H-xanthen-9-ones 5a–s, 12n–s and 13b–s, the signals corre-

sponding to 1-H and 4-H appear as singlets at δ = 7.91–

We have reported two different routes for the synthesis

8.38 and 7.43–7.65 ppm, respectively; the high-frequency of hydroxylated 2,3-diaryl-9H-xanthen-9-ones. One of them

values of the 1-H protons are due to the anisotropic and involves Heck reactions between 3-bromo-2-methyl-4H-

mesomeric deshielding effects of the carbonyl groups. In the chromen-4-one and styrenes, followed by aldol condensa-

case of the xanthones 12n–s and 13n–s it was also possible tions of the obtained compounds with benzaldehyde to gave

to identify the singlets corresponding to the resonances of 2,3-distyryl-4H-chromen-4-ones, which gave the desired 2,3-

the 8-hydroxy groups at δ = 12.48–12.92 ppm. The high- diaryl-9H-xanthen-9-ones after electrocyclisation and oxi-

frequency values of these resonances are due to intramolec- dation processes. In the second route, the 2,3-diaryl-9H-

ular hydrogen bonding of the hydroxy protons with the car- xanthen-9-ones were obtained through Heck reactions be-

bonyl groups. For compounds 13b–n, the signals corre- tween 3-bromo-2-styryl-4H-chromen-4-ones and styrenes.

sponding to the proton resonance of the hydroxy groups The 3-bromo-2-styryl-4H-chromen-4-ones were obtained

also appear as singlets, at high-frequency values, with chem- either through aldol condensations between 3-bromo-2-

ical shifts higher than 8.9 ppm.

methyl-4H-chromen-4-one and benzaldehydes or through

The correlations found in the HMBC spectra provided Baker–Venkataraman rearrangements of 2-acetylphenyl

unequivocal support for the structures of the 2,3-diaryl-9H- cinnamates followed by one-pot bromination/cyclisation

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2647

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

4b or 4c) was added to a mixture of the appropriate 3-bromo-2-

styryl-4H-chromen-4-one (3a or 3b, 0.6 mmol), triphenylphos-

phane (15.7 mg, 0.06 mmol), tetrakis(triphenylphosphane)palla-

dium(0) (34.7 mg, 0.03 mmol) and triethylamine (83.6 µL,

0.6 mmol) in N-methyl-2-pyrrolidin-1-one (10 mL). The mixture

was stirred under different time and temperature conditions ac-

cording to the substitution on the compounds (Table 2). The mix-

ture was then poured into water (20 mL) and ice (10 g) and ex-

tracted with diethyl ether (4 ϫ 25 mL) and dried with anhydrous

sodium sulfate. The residue was concentrated, taken up in dichloro-

methane (5 mL) and purified by thin layer chromatography (eluent:

dichloromethane/light petroleum, 7:3). The major spot with higher

R_fvalue corresponds to the 2,3-diaryl-9H-xanthen-9-one (5a–f)

and a minor spot with lower R_fcorresponds to the 2,3-diaryl-3,4-

dihydro-9H-xanthen-9-one (6a–f). The 2,3-diaryl-9H-xanthen-9-

ones 5a–f were recrystallised from ethanol and obtained in moder-

ate to good yields.

with phenyltrimethylammonium tribromide. The cleavage

of the methyl and benzyl protecting groups with boron tri-

bromide gave the desired hydroxylated 2,3-diaryl-9H-

xanthen-9-ones.

Experimental Section

General Remarks: Melting points were measured in a Reichert

Thermovar apparatus fitted with a microscope and are uncor-

rected. NMR spectra were recorded on a Bruker Avance 300 spec-

1

trometer (300.13 MHz for H and 75.47 MHz for ¹³C), in CDCl₃

as solvent if not stated otherwise. Chemical shifts (δ) are reported

in ppm and coupling constants (J) in Hz; the internal standard was

TMS. Unequivocal ¹³C assignments were made with the aid of 2D

gHSQC and gHMBC (delays for one-bond and long-range J C/H

couplings were optimised for 145 and 7 Hz, respectively) experi-

ments. Positive-ion ESI mass spectra were acquired with a Q-

TOF 2 instrument [dilution of 1 µL of the sample in chloroform

solution (ca. 10^–5) in 200 µL of 0.1% trifluoroacetic acid/meth-

anol solution. Nitrogen was used as nebuliser gas and argon as

collision gas. The needle voltage was set at 3000 V, with the ion

source at 80 °C and the desolvation temperature at 150 °C. The

cone voltage was 35 V]. Other low- and high-resolution mass spec-

tra (EI, 70 eV) were measured with VG Autospec Q and M spec-

trometers. Elemental analyses were obtained with a LECO 932

CHNS analyser. Preparative thin-layer chromatography was per-

formed with Merck silica gel (60 DGF₂₅₄). Column chromatog-

raphy was performed with Merck silica gel (60, 70–230 mesh). All

chemicals and solvents used were obtained from commercial

sources and used as received or dried by standard procedures.

2,3-Diaryl-9H-xanthen-9-ones 5a and 5b and 2,3-Diphenyl-3,4-dihy-

dro-9H-xanthen-9-ones 6a and 6f: These compounds were shown to

possess spectroscopic and analytical data identical to those pre-

viously reported.^[26]

2-(4-Methoxyphenyl)-3-phenyl-3,4-dihydro-9H-xanthen-9-one (6b):

1

M.p. 153–156 °C. H NMR: δ = 2.99 (dd, J = 17.3, 1.3 Hz, 1 H,

4_trans-H), 3.64 (dd, J = 17.3, 9.0 Hz, 1 H, 4_cis-H), 3.77 (s, 3 H, 4Ј-

OCH₃), 4.27 (dd, J = 9.0, 1.3 Hz, 1 H, 3-H), 6.81 (d, J = 8.9 Hz,

2 H, 3Ј,5Ј-H), 7.15–7.40 (m, 7 H, 5,7,2ЈЈ,3ЈЈ,4ЈЈ,5ЈЈ,6ЈЈ-H), 7.43 (d,

J = 8.9 Hz, 2 H, 2Ј,6Ј-H), 7.46 (s, 1 H, 1-H), 7.58 (dt, J = 7.8,

1.6 Hz, 1 H, 6-H), 8.28 (dd, J = 7.8, 1.6 Hz, 1 H, 8-H) ppm. ¹³C

NMR: δ = 36.6 (C-4), 41.6 (C-3), 55.2 (4Ј-OCH₃), 113.8 (C-3Ј,5Ј),

114.8 (C-1), 117.0 (C-9a), 118.0 (C-5), 123.8 (C-8a), 125.0 (C-7),

126.1 (C-8), 126.8 (C-2Ј,6Ј), 127.1 (C-4ЈЈ), 127.3 (C-2ЈЈ,6ЈЈ), 128.9

(C-3ЈЈ,5ЈЈ), 131.5 (C-1Ј), 132.9 (C-6), 134.9 (C-2), 140.8 (C-1ЈЈ),

155.8 (C-4b), 159.1 (C-4Ј), 162.0 (C-4a), 174.2 (C-9) ppm. EI-MS:

m/z (%) = 380 (100) [M]^+·, 379 (18), 378 (31), 365 (6), 347 (3), 303

(23), 287 (6), 273 (16), 260 (10), 215 (9), 202 (6), 190 (6), 165 (3),

139 (3), 121 (14), 108 (3), 92 (5), 77 (6), 65 (4), 51 (4). HRMS (EI):

calcd. for C₂₆H₂₀O₃[M]^+·380.1412; found 380.1412.

Synthesis of (E)-3-Bromo-2-styryl-4H-chromen-4-ones 3a and 3b:

Sodium (0.4 g, 16.7 mmol) was gradually added to dry methanol

(20 mL) and the mixture was stirred until the reaction mixture had

returned to room temperature. 3-Bromo-2-methyl-4H-chromen-4-

one (1, 1.0 g, 4.2 mmol) and the appropriate benzaldehyde 2a or

2b (5.0 mmol) were added and the reaction mixture was allowed to

stand at room temperature for 48 h. After this period, the solution

was poured into ice (100 g) and water (100 mL) and the pH was

adjusted to 4 with hydrochloric acid. The yellow solid was removed

by filtration, taken up in dichloromethane and purified by silica

gel column chromatography with dichloromethane as eluent. The

solvent was removed to dryness and the residue was recrystallised

from ethanol to give the (E)-3-bromo-2-styryl-4H-chromen-4-ones

3a or 3b.

2-(3,4-Dimethoxyphenyl)-3-phenyl-9H-xanthen-9-one (5c): M.p.

1

139–140 °C. H NMR: δ = 3.56 and 3.87 (2ϫs, 6 H, 3Ј,4Ј-OCH₃),

6.54 (d, J = 1.9 Hz, 1 H, 2Ј-H), 6.78–6.90 (m, 2 H, 5ЈH and 6Ј-H),

7.20–7.24 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.26–7.32 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.40

(dt, J = 7.6, 1.0 Hz, 1 H, 7-H), 7.52 (d, J = 8.2 Hz, 1 H, 5-H), 7.55

(s, 1 H, 4-H), 7.74 (ddd, J = 8.2, 7.6, 1.7 Hz, 1 H, 6-H), 8.38 (dd,

J = 7.6, 1.7 Hz, 1 H, 8-H), 8.39 (s, 1 H, 1-H) ppm. ¹³C NMR: δ =

55.7 and 55.9 (3Ј,4Ј-OCH₃), 110.7 (C-5Ј), 113.4 (C-2Ј), 118.0 (C-5),

119.5 (C-4), 120.7 (C-9a), 121.9 (C-8a), 122.1 (C-6Ј), 123.9 (C-7),

126.7 (C-8), 127.5 (C-4ЈЈ), 128.7 (C-1), 128.2 (C-3ЈЈ,5ЈЈ), 129.5 (C-

2ЈЈ,6ЈЈ), 132.2 (C-1Ј), 134.8 (C-6), 136.7 (C-2), 140.1 (C-1ЈЈ), 147.6

(C-3), 148.0 and 148.1 (C-3Ј, C-4Ј), 155.0 (C-4a), 156.2 (C-4b),

177.0 (C-9) ppm. EI-MS: m/z (%) = 408 [M]^+·(100), 393 (9), 361

(8), 333 (8), 321 (7), 292 (4), 263 (3), 204 (4), 188 (3), 167 (4), 138

(2), 77 (1). C₂₇H₂₀O₄(408.45): calcd. for C 79.40, H 4.94; found C

79.64, H 4.83.

(E)-3-Bromo-2-(2-phenylvinyl)-4H-chromen-4-one (3a): Yield 1.42 g

(87%); m.p. 167–169 °C. ¹H NMR: δ = 7.40–7.49 (m, 4 H, 6-H,

3Ј,4Ј,5Ј-H), 7.51 (d, J = 16.0 Hz, 1 H, α-H), 7.56 (d, J = 7.9 Hz, 1

H, 8-H), 7.64–7.67 (m, 2 H, 2Ј,6Ј-H), 7.72 (dt, J = 7.9, 1.7 Hz, 1

H and 7-H), 7.73 (d, J = 16.0 Hz, 1 H, β-H), 8.25 (dd, J = 8.0,

1.7 Hz, 1 H, 5-H) ppm. ¹³C NMR: δ = 109.8 (C-3), 117.5 (C-8),

119.2 (C-α), 122.1 (C-10), 125.4 (C-6), 126.4 (C-5), 128.1 (C-2Ј,6Ј),

129.1 (C-3Ј,5Ј), 130.3 (C-4Ј), 134.1 (C-7), 134.9 (C-1Ј), 139.6 (C-β),

154.9 (C-9), 158.4 (C-2), 172.8 (C-4) ppm. EI-MS: m/z (%) = 328

[M]^+·(⁸¹Br, 22), 326 [M]^+·(⁷⁹Br, 22), 282 (10), 247 (100), 218 (12),

191 (11), 189 (12), 165 (4), 127 (24), 109 (7), 101 (3), 92 (10), 77

(9), 63 (6), 51 (4). C₁₇H₁₁BrO₂(327.13): calcd. C 62.41, H 3.39;

found C 62.49, H 3.42.

2-(3,4-Dimethoxyphenyl)-3-phenyl-3,4-dihydro-9H-xanthen-9-one

1

(6c): Yellowish oil. H NMR: δ = 3.00 (dd, J = 17.3, 1.5 Hz, 1 H,

4_trans-H), 3.65 (dd, J = 17.3, 9.1 Hz, 1 H, 4_cis-H), 3.84 (s, 6 H, 3Ј,4Ј-

OCH₃), 4.29 (dd, J = 9.1, 1.5 Hz, 1 H, 3-H), 6.74 (d, J = 8.4 Hz,

1 H, 5Ј-H), 6.96 (dd, J = 8.4, 2.2 Hz, 1 H, 6Ј-H), 7.09 (d, J =

2.2 Hz, 1 H, 2Ј-H), 7.18–7.32 (m, 5 H, 2ЈЈ,3ЈЈ,4ЈЈ,5ЈЈ,6ЈЈ-H), 7.33–

7.41 (m, 2 H, 5-H, 7-H), 7.46 (s, 1 H, 1-H), 7.59 (dt, J = 7.8, 1.6 Hz,

1 H, 6-H), 8.28 (dd, J = 8.0, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ

= 36.5 (C-4), 41.8 (C-3), 55.8 (3Ј,4Ј-OCH₃), 108.7 (C-2Ј), 110.8 (C-

(E)-4Ј-Benzyloxy-3-bromo-2-(2-phenylvinyl)-4H-chromen-4-one

(3b): This compound was shown to possess spectroscopic and ana-

lytical data identical to those previously reported.^[26]

Synthesis of the 2,3-Diaryl-9H-xanthen-9-ones 5a–f: The appropri-

ate styrene (4a–c, 3 mmol for styrene 4a and 0.8 mmol for styrenes

2648

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

5Ј), 115.0 (C-1), 116.9 (C-9a), 117.9 (C-5), 118.2 (C-6Ј), 123.8 (C-

1.4 Hz, 1 H, 4_trans-H), 3.60 (dd, J = 17.3, 8.4 Hz, 1 H, 4_cis-H), 3.77

8a), 125.0 (C-7), 126.1 (C-8), 127.1 (C-4ЈЈ), 127.2 (C-2ЈЈ,6ЈЈ), 128.9 (s, 3 H, 4Ј-OCH₃), 4.22 (brd, J = 8.4 Hz, 1 H, 3-H), 4.94 (s, 2 H,

(C-3ЈЈ,5ЈЈ), 131.9 (C-1Ј), 133.0 (C-6), 135.1 (C-2), 140.9 (C-1ЈЈ), 4ЈЈ-OCH₂C₆H₅), 6.81 (d, J = 8.9 Hz, 1 H, 3Ј,5Ј-H), 6.84 (d, J =

148.70 and 148.72 (C-3Ј,4Ј), 155.8 (C-4b), 162.1 (C-4a), 174.2 (C-

9) ppm. EI-MS: m/z = 410 [M]^+·(100), 409 (8), 408 (20), 395 (7),

379 (4), 361 (3), 333 (15), 319 (4), 289 (4), 273 (13), 205 (5), 165

(12), 151 (6), 138 (5), 121 (9), 92 (4), 77 (5). HRMS (EI): calcd. for

C₂₇H₂₂O₄[M]^+·410.1518; found 410.1521.

8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.20 (d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.28–

7.39 (m, 7 H, 5-H, 7-H, 2,3,4,5,6-H of 4ЈЈ-OCH₂C₆H₅), 7.43 (s, 1

H, 1-H), 7.43 (d, J = 8.9 Hz, 2 H, 2Ј,6Ј-H), 7.58 (dt, J = 7.8, 1.6 Hz,

1 H, 6-H), 8.27 (dd, J = 8.0, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ

= 36.7 (C-4), 40.8 (C-3), 55.2 (4Ј-OCH₃), 69.8 (4ЈЈ-OCH₂C₆H₅),

113.8 (C-3Ј,5Ј), 114.5 (C-1), 115.0 (C-3ЈЈ,5ЈЈ), 116.9 (C-9a), 117.9

(C-5), 123.8 (C-8a), 124.9 (C-7), 126.1 (C-8), 126.8 (C-2Ј,6Ј), 127.4

(C-2,6 of 4ЈЈ-OCH₂C₆H₅), 127.9 (C-4 of 4ЈЈ-OCH₂C₆H₅), 128.3 (C-

2ЈЈ,6ЈЈ), 128.5 (C-3,5 of 4ЈЈ-OCH₂C₆H₅), 131.5 (C-1Ј), 132.87 (C-

6), 132.90 (C-1ЈЈ), 135.2 (C-2), 136.8 (C-1 of 4ЈЈ-OCH₂C₆H₅), 155.8

(C-4b), 157.9 (C-4ЈЈ), 155.9 (C-4Ј), 162.1 (C-4a), 174.2 (C-9) ppm.

EI-MS: m/z (%) = 486 [M]^+·(44), 485 (7), 484 (9), 408 (6), 395 (15),

364 (3), 302 (5), 213 (3), 135 (33), 121 (8), 92 (14), 91 (100), 77

(7), 65 (9). HRMS (EI): calcd. for C₃₃H₂₆O₄[M]^+·486.1831; found

486.1829.

3-(4-Benzyloxyphenyl)-2-phenyl-9H-xanthen-9-one (5d): M.p. 182–

1

183 °C. H NMR: δ = 5.05 (s, 2 H, 4ЈЈ-OCH₂C₆H₅), 6.88 (d, J =

8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.13 (d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.18–

7.27 (m, 5 H, 2Ј,3Ј,4Ј,5Ј,6Ј-H), 7.33–7.45 (m, 6 H, 7-H, 2,3,4,5,6-H

of 4ЈЈ-OCH₂C₆H₅), 7.52 (d, J = 7.9 Hz, 1 H, 5-H), 7.54 (s, 1 H, 4-

H), 7.74 (dt, J = 7.9, 1.6 Hz, 1 H, 6-H), 8.35 (s, 1 H, 1-H), 8.37

(dd, J = 7.9, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 70.0 (4ЈЈ-

OCH₂C₆H₅), 114.5 (C-3ЈЈ,5ЈЈ), 118.0 (C-5), 119.2 (C-4), 120.4 (C-

9a), 122.0 (C-8a), 123.9 (C-7), 126.76 (C-8), 126.84 (C-4Ј), 127.5

(C-2,6 of 4ЈЈ-OCH₂C₆H₅), 128.0 (C-4 of 4ЈЈ-OCH₂C₆H₅), 128.1 (C-

2Ј,6Ј), 128.4 (C-1), 128.6 (C-3,5 of 4ЈЈ-OCH₂C₆H₅), 129.9 (C-3Ј,5Ј),

130.9 (C-2ЈЈ,6ЈЈ), 132.4 (C-1ЈЈ), 134.7 (C-6), 136.7 (C-1 of 4ЈЈ-

OCH₂C₆H₅), 137.0 (C-1Ј), 140.0 (C-2), 147.3 (C-3), 155.3 (C-4a),

156.3 (C-4b), 158.4 (C-4ЈЈ), 177.0 (C-9) ppm. EI-MS: m/z (%) =

454 [M]^+·(33), 408 (2), 363 (8), 333 (2), 305 (3), 236 (3), 91 (100),

65 (3). C₃₂H₂₂O₃(454.52): calcd. for C 84.56, H 4.88; found C

84.29, H 4.87.

3-(4-Benzyloxyphenyl)-2-(3,4-dimethoxyphenyl)-9H-xanthen-9-one

1

(5f): M.p. 188–189 °C. H NMR: δ = 3.61 (s, 3 H, 4Ј-OCH₃), 3.89

(s, 3 H, 3Ј-OCH₃), 5.06 (s, 2 H, 4ЈЈ-OCH₂C₆H₅), 6.59 (d, J =

1.8 Hz, 1 H, 2Ј-H), 6.79–6.86 (m, 2 H, 5Ј-H, 6Ј-H), 6.90 (d, J =

8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.15 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.31–

7.46 (m, 6 H, 7-H, 4ЈЈ-OCH₂C₆H₅), 7.52 (d, J = 7.9 Hz, 1 H, 5-H),

7.53 (s, 1 H, 4-H), 7.75 (dt, J = 7.9, 1.8 Hz, 1 H, 6-H), 8.36 (s, 1

H, 1-H), 8.38 (dd, J = 8.2, 1.8 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ =

55.6 (4Ј-OCH₃), 55.8 (3Ј-OCH₃), 69.9 (4ЈЈ-OCH₂C₆H₅), 110.8 (C-

5Ј), 113.4 (C-2Ј), 114.6 (C-3ЈЈ,5ЈЈ), 118.0 (C-5), 119.2 (C-4), 120.4

(C-9a), 121.9 (C-8a), 122.2 (C-6Ј), 123.9 (C-7), 126.8 (C-8), 127.4

(C-2,6 of 4ЈЈ-OCH₂C₆H₅), 127.9 (C-1), 128.0 (C-4 of 4ЈЈ-

OCH₂C₆H₅), 128.6 (C-3,5 of 4ЈЈ-OCH₂C₆H₅), 130.8 (C-2ЈЈ,6ЈЈ),

132.5 (C-1Ј), 132.7 (C-1ЈЈ), 134.7 (C-6), 136.7 (C-2, C-1 of 4ЈЈ-

OCH₂C₆H₅), 147.3 (C-3), 148.0 (C-3Ј), 148.2 (C-4Ј), 155.1 (C-4a),

156.3 (C-4b), 158.3 (C-4ЈЈ), 177.0 (C-9) ppm. EI-MS: m/z (%) =

514 [M]^+·(11), 388 (11), 166 (11), 165 (13), 91 (100), 77 (3), 65 (5).

HRMS (EI): calcd. for C₃₄H₂₆O₅[M]^+·514.1780; found 514.1785.

3-(4-Benzyloxyphenyl)-2-phenyl-3,4-dihydro-9H-xanthen-9-one (6d):

1

Yellowish oil. H NMR: δ = 2.97 (dd, J = 17.4, 1.5 Hz, 1 H, 4_trans

-

H), 3.63 (dd, J = 17.4, 8.4 Hz, 1 H, 4_cis-H), 4.26 (brd, J = 8.4 Hz,

1 H, 3-H), 4.95 (s, 2 H, 4ЈЈ-OCH₂C₆H₅) 6.85 (d, J = 8.7 Hz, 2 H,

3ЈЈ,5ЈЈ-H), 7.22 (d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.24–7.41 (m, 10 H,

5,7,3Ј,4Ј,5Ј-H, 2,3,4,5,6-H of 4ЈЈ-OCH₂C₆H₅), 7.46 (m, 2 H, 2Ј,6Ј-

H), 7.54 (s, 1 H, 1-H), 7.59 (dt, J = 7.8, 1.6 Hz, 1 H, 6-H), 8.28

(dd, J = 7.9, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 36.8 (C-4),

40.9 (C-3), 69.9 (4ЈЈ-OCH₂C₆H₅), 115.1 (C-3ЈЈ,5ЈЈ), 116.5 (C-1),

116.8 (C-9a), 118.0 (C-5), 123.9 (C-8a), 125.0 (C-7), 125.6 (C-2Ј,6Ј),

126.2 (C-8), 127.49 (C-2,6 of 4ЈЈ-OCH₂C₆H₅), 127.52 (C-4Ј), 127.9

(C-4 of 4ЈЈ-OCH₂C₆H₅), 128.41, 128.44 and 128.5 (C-3Ј,5Ј, C-

2ЈЈ,6ЈЈ, C-3,5 of 4ЈЈ-OCH₂C₆H₅), 132.8 (C-1ЈЈ), 133.0 (C-6), 135.6

(C-2), 136.8 (C-1 of 4ЈЈ-OCH₂C₆H₅), 139.1 (C-1Ј), 155.8 (C-4b),

157.9 (C-4ЈЈ), 162.6 (C-4a), 174.2 (C-9) ppm. EI-MS: m/z (%) = 456

[M]^+·(59), 455 (11), 454 (9), 379 (4), 365 (20), 289 (5), 272 (13),

215 (5), 121 (4), 92 (11), 91 (100), 77 (3), 65 (8). HRMS (EI): calcd.

for C₃₂H₂₄O₃[M]^+·456.1725; found 456.1725.

Synthesis of the (E)-2-Methyl-3-styryl-4H-chromen-4-ones 7a–c:

The appropriate styrene (4a–c, 2.5 mmol) was added to a mixture

of 3-bromo-2-methyl-4H-chromen-4-one (1, 0.12 g, 0.5 mmol), tri-

phenylphosphane (13.1 mg, 0.05 mmol), palladium chloride

(4.4 mg, 0.025 mmol) and triethylamine (69.7 µL, 0.5 mmol) in N-

methyl-2-pyrrolidin-1-one (5 mL). The mixture was stirred at

160 °C for 9 h. It was then poured into water (15 mL) and ice

(10 g), extracted with diethyl ether (4ϫ25 mL) and dried with an-

hydrous sodium sulfate. The residue was concentrated, taken up in

dichloromethane (10 mL) and purified by thin layer chromatog-

raphy (eluent: dichloromethane/light petroleum 7:3). The obtained

(E)-2-methyl-3-styryl-4H-chromen-4-ones (7a–c) were recrystallised

from ethanol and obtained in moderate to good yields.

3-(4-Benzyloxyphenyl)-2-(4-methoxyphenyl)-9H-xanthen-9-one (5e):

1

M.p. 140–142 °C. H NMR: δ = 3.81 (s, 3 H, 4Ј-OCH₃), 5.06 (s, 2

H, 4ЈЈ-OCH₂C₆H₅), 6.80 (d, J = 8.8 Hz, 2 H, 3Ј,5Ј-H), 6.90 (d, J

= 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.11 (d, J = 8.8 Hz, 2 H, 2Ј,6Ј-H), 7.15

(d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.34–7.46 (m, 6 H, 7-H, 4ЈЈ-

OCH₂C₆H₅), 7.520 (d, J = 7.8 Hz, 1 H, 5-H), 7.522 (s, 1 H, 4-H),

7.74 (dt, J = 7.8, 1.6 Hz, 1 H, 6-H), 8.32 (s, 1 H, 1-H), 8.37 (dd, J

= 8.0, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 55.2 (4Ј-OCH₃), 70.0

(4ЈЈ-OCH₂C₆H₅), 113.6 (C-3Ј,5Ј), 114.5 (C-3ЈЈ,5ЈЈ), 118.0 (C-5),

119.2 (C-4), 120.4 (C-9a), 122.0 (C-8a), 123.9 (C-7), 126.8 (C-8),

127.6 (C-2,6 of 4ЈЈ-OCH₂C₆H₅), 128.1 (C-4 of 4ЈЈ-OCH₂C₆H₅),

128.2 (C-1), 128.6 (C-3,5 of 4ЈЈ-OCH₂C₆H₅), 130.9 (C-2ЈЈ,6ЈЈ),

131.0 (C-2Ј,6Ј), 132.4 (C-1Ј), 132.6 (C-1ЈЈ), 134.7 (C-6), 136.65 (C-

2), 136.72 (C-1 of 4ЈЈ-OCH₂C₆H₅), 147.3 (C-3), 155.1 (C-4a), 156.3

(C-4b), 158.3 (C-4ЈЈ), 158.6 (C-4Ј), 177.1 (C-9) ppm. EI-MS: m/z

(%) = 484 [M]^+·(61), 394 (15), 393 (23), 91 (100), 85 (6). C₃₃H₂₄O₄

(484.54): calcd. for C 81.80, H 4.99; found C 82.02, H 5.06.

(E)-2-Methyl-3-(2-phenylvinyl)-4H-chromen-4-one (7a): Yield

6.30 mg (48%); m.p. 136–137 °C. ¹H NMR: δ = 2.62 (s, 3 H, 2-

CH₃), 6.97 (d, J = 16.3 Hz, 1 H, α-H), 7.24–7.29 (m, 1 H, 4Ј-H),

7.36 (d, J = 7.7 Hz, 2 H, 3Ј,5Ј-H), 7.38 (ddd, J = 8.0, 7.9, 1.0 Hz,

2 H, 6-H), 7.41 (d, J = 8.2 Hz, 1 H, 8-H), 7.53 (dd, J = 7.7, 1.5 Hz,

2 H, 2Ј,6Ј-H), 7.63 (ddd, J = 8.2, 8.0, 1.6 Hz, 1 H, 7-H), 7.71 (d, J

= 16.3 Hz, 1 H, β-H), 8.25 (dd, J = 7.9, 1.6 Hz, 1 H, 5-H) ppm.

¹³C NMR: δ = 19.3 (2-CH₃), 117.5 (C-8), 118.5 (C-3), 119.4 (C-α),

123.4 (C-10), 124.8 (C-6), 126.1 (C-5), 126.4 (C-2Ј,6Ј), 127.7 (C-4Ј),

128.6 (C-3Ј,5Ј), 133.1 (C-7), 134.2 (C-β), 137.9 (C-1Ј), 155.2 (C-9),

163.8 (C-2), 176.9 (C-4) ppm. EI-MS: m/z (%) = 262 [M]^+·(100),

247 (39), 233 (7), 218 (5), 202 (3), 191 (5), 185 (63), 141 (27), 121

(14), 115 (21), 102 (3), 92 (11), 77 (8), 63 (10), 51 (6). C₁₈H₁₄O₂

(262.30): calcd. for C 82.42, H 5.38; found C 82.31, H 5.46.

3-(4-Benzyloxyphenyl)-2-(4-methoxyphenyl)-3,4-dihydro-9H-

xanthen-9-one (6e): Yellowish oil. ¹H NMR: δ = 2.95 (dd, J = 17.3,

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2649

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

(E)-3-[2-(4-Methoxyphenyl)vinyl]-2-methyl-4H-chromen-4-one (7b): 2Ј,6Ј-H), 7.32–7.41 (m, 4 H, 7,3ЈЈ,4ЈЈ,5ЈЈ-H), 7.48 (d, J = 8.4 Hz, 1

1

Yield 71.6 mg (49%); m.p. 89–91 °C. H NMR: δ = 2.61 (s, 3 H, H, 5-H), 7.50–7.53 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.60–7.66 (m, 1 H, 6-H),

2-CH₃), 3.83 (s, 3 H, 4Ј-OCH₃), 6.83 (d, J = 16.3 Hz, 1 H, α-H), 8.16 (dd, J = 8.1, 1.1 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 28.2 (C-

6.90 (d, J = 8.7 Hz, 2 H, 3Ј,5Ј-H), 7.35–7.43 (m, 2 H, 6-H, 8-H),

7.47 (d, J = 8.7 Hz, 2 H, 2Ј,6Ј-H), 7.60–7.67 (m, 1 H, 7-H), 7.64 125.7 (C-8), 126.8 (C-2ЈЈ,6ЈЈ), 127.0 (C-4Ј), 127.2 (C-2Ј,6Ј), 128.8

(d, J = 16.3 Hz, 1 H, β-H), 8.25 (dd, J = 8.1, 0.9 Hz, 1 H, 5- (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 129.3 (C-4ЈЈ), 133.0 (C-6), 138.1 (C-1ЈЈ), 140.7

H) ppm. ¹³C NMR: δ = 19.3 (2-CH₃), 55.3 (4Ј-OCH₃), 114.0 (C- (C-1Ј), 150.6 (C-3), 155.6 (C-4a), 159.6 (C-4b), 176.7 (C-9) ppm.

3Ј,5Ј), 117.3 (C-8), 117.5 (C-α), 118.7 (C-3), 123.4 (C-10), 124.8 (C-

EI-MS: m/z (%) = 350 [M]^+·(84), 349 (52), 274 (55), 273 (100), 261

6), 126.1 (C-5), 127.7 (C-2Ј,6Ј), 130.7 (C-1Ј), 133.1 (C-7), 133.8 (C- (14), 228 (10), 215 (12), 202 (8), 189 (6), 152 (10), 139 (7), 121 (12),

β), 155.3 (C-9), 159.3 (C-4Ј), 163.3 (C-2), 177.0 (C-4) ppm. EI-MS: 115 (11), 105 (33), 92 (8), 91 (6), 77 (23), 63 (7), 51 (12). HRMS

m/z (%) = 292 [M]^+·(31), 277 (14), 211 (8), 197 (10), 183 (11), 169 (EI): calcd. for C₂₅H₁₈O₂[M]^+·350.1307; found 350.1306.

1), 41.5 (C-2), 111.5 (C-9a), 118.4 (C-4), 124.1 (C-8a), 124.7 (C-7),

(13), 155 (17), 141 (19), 127 (24), 125 (10), 113 (28), 111 (16), 99

(34), 97 (27), 85 (96), 83 (20), 71 (100), 69 (18). HRMS (EI): calcd.

for C₁₉H₁₆O₃[M]^+·292.1099; found 292.1091.

(E,E)-2-[2-(4-Methoxyphenyl)vinyl]-3-(2-phenylvinyl)-4H-chromen-

4-one (8b): Yield 1.07 g (67%); m.p. 163–164 °C. ¹H NMR: δ =

3.85 (s, 3 H, 4ЈЈ-OCH₃), 6.93 (d, J = 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.11

(d, J = 16.4 Hz, 1 H, αЈ-H), 7.36 (d, J = 16.4 Hz, 1 H, βЈ-H), 7.36–

7.42 (m, 4 H, 6-H, 3Ј,4Ј,5Ј-H), 7.42 (d, J = 16.0 Hz, 1 H, α-H),

7.52 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.51–7.52 (m, 1 H, 8-H), 7.60

(dd, J = 7.9, 1.7 Hz, 2 H, 2Ј,6Ј-H), 7.68 (dt, J = 7.8, 1.6 Hz, 1 H,

7-H), 7.70 (d, J = 16.0 Hz, 1 H, β-H), 8.25 (dd, J = 8.0, 1.6 Hz, 1

H, 5-H) ppm. ¹³C NMR: δ = 55.3 (4ЈЈ-OCH₃), 114.1 (5ЈЈ, C-3ЈЈ),

116.9 (C-αЈ), 117.5 (C-8), 118.8 (C-α), 119.5 (C-3), 123.1 (C-10),

124.7 (C-6), 126.1 (C-5), 127.7 (C-2Ј,6Ј), 128.0 (C-2ЈЈ,6ЈЈ), 129.0 (C-

3Ј,5Ј), 129.4 (C-4Ј), 130.4 (C-1ЈЈ), 133.5 (C-7), 135.6 (C-1Ј), 135.8

(C-βЈ), 136.8 (C-β), 155.1 (C-9), 157.7 (C-2), 159.6 (C-4ЈЈ), 177.7

(C-4) ppm. EI-MS: m/z (%) = 380 [M]^+·(100), 303 (65), 289 (6),

273 (41), 260 (11), 215 (13), 202 (7), 190 (6), 151 (7), 121 (48), 115

(7), 92 (9), 77 (9), 63 (6), 51 (4). C₂₆H₂₀O₃(380.44): calcd. for C

82.08, H 5.30; found C 82.05, H 4.99.

(E)-3-[2-(3,4-Dimethoxyphenyl)vinyl]-2-methyl-4H-chromen-4-one

1

(7c): Yield 83.8 mg (52%); m.p. 117–118 °C. H NMR: δ = 2.61 (s,

3 H, 2-CH₃), 3.90 and 3.93 (2ϫs, 6 H, 3Ј,4Ј-OCH₃), 6.77–6.92 (m,

1 H, 5Ј-H), 6.84 (d, J = 16.3 Hz, 1 H, α-H), 7.06–7.07 (m, 2 H,

2Ј,6Ј-H), 7.35–7.41 (m, 2 H, 6-H, 8-H), 7.59 (d, J = 16.3 Hz, 1 H,

β-H), 7.59–7.65 (m, 1 H, 7-H), 8.24 (dd, J = 7.7, 1.2 Hz, 1 H, 5-

H) ppm. ¹³C NMR: δ = 19.4 (2-CH₃), 55.8 and 55.9 (3Ј,4Ј-OCH₃),

109.0 (C-2Ј), 111.0 (C-5Ј), 117.5 (C-8, C-α), 118.6 (C-3), 119.4 (C-

6Ј), 123.2 (C-10), 124.7 (C-6), 126.0 (C-5), 130.9 (C-1Ј), 133.1 (C-

7), 134.0 (C-β), 148.8 and 148.9 (C-3Ј,4Ј), 155.2 (C-9), 163.3 (C-2),

176.9 (C-4) ppm. EI-MS: m/z (%) = 322 [M]^+·(100), 307 (30), 292

(6), 276 (6), 263 (6), 247 (7), 235 (9), 221 (3), 202 (3), 185 (17), 161

(9), 144 (5), 138 (7), 121 (10), 115 (15), 92 (13), 77 (7), 63 (9), 51

(6). C₂₀H₁₈O₄(322.35): calcd. for C 74.52, H 5.63; found C 74.36,

H 5.86.

(E,E)-2-[2-(3,4-Dimethoxyphenyl)vinyl]-3-(2-phenylvinyl)-4H-

chromen-4-one (8c): Yield 1.19 g (69 %); m.p. 128–130 °C. ¹H

NMR: δ = 3.93 and 3.96 (s, 6 H, 3ЈЈ,4ЈЈ-OCH₃), 6.89 (d, J = 8.2 Hz,

1 H, 5ЈЈ-H), 7.11 (dd, J = 8.2, 1.9 Hz, 1 H, 6ЈЈ-H), 7.13 (d, J =

16.1 Hz, 1 H, αЈ-H), 7.14 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.27 (d, J =

16.1 Hz, 1 H, βЈ-H), 7.38–7.42 (m, 4 H, 6,3Ј,4Ј,5Ј-H), 7.42 (d, J =

15.8 Hz, 1 H, α-H), 7.54 (d, J = 8.0 Hz, 1 H, 8-H), 7.61 (d, J =

7.3 Hz, 2 H, 2Ј,6Ј-H), 7.69 (dt, J = 8.0, 1.5 Hz, 1 H, 7-H), 7.71 (d,

J = 15.8 Hz, 1 H, β-H), 8.25 (dd, J = 8.0, 1.5 Hz, 1 H, 5-H). ¹³C

NMR: δ = 55.9 (3ЈЈ,4ЈЈ-OCH₃), 109.1 (C-2ЈЈ), 111.1 (C-5ЈЈ), 117.2

(C-αЈ), 117.6 (C-8), 118.9 (C-α), 119.6 (C-3), 120.0 (C-6ЈЈ), 123.1

(C-10), 124.7 (C-6), 126.1 (C-5), 127.6 (C-2Ј,6Ј), 129.0 (C-3Ј,5Ј),

129.6 (C-4Ј), 130.7 (C-1ЈЈ), 133.6 (C-7), 135.6 (C-1Ј), 136.1 (C-βЈ),

136.8 (C-β), 149.1 (C-3ЈЈ), 149.2 (C-4ЈЈ), 155.1 (C-9), 157.8 (C-2),

177.7 (C-4) ppm. EI-MS: m/z (%) = 410 [M]^+·(100), 333 (29), 317

(6), 289 (3), 273 (27), 261 (4), 215 (6), 202 (10), 189 (5), 151 (31),

138 (10), 121 (11), 92 (10), 77 (8), 63 (5), 51 (5). C₂₇H₂₂O₄(410.46):

calcd. for C 79.01, H 5.40; found C 78.75, H 5.55.

Synthesis of the (E,E)-2,3-Distyryl-4H-chromen-4-ones 8a–c: So-

dium (0.4 g, 16.7 mmol) was gradually added to dry methanol

(20 mL) and the mixture was stirred until the reaction mixture had

reached room temperature. The appropriate (E)-2-methyl-3-styryl-

4H-chromen-4-one (7a–c, 4.2 mmol) and benzaldehyde (2a, 0.53 g,

5.0 mmol) were added and the reaction mixture was allowed to

stand at room temperature for 48 h. After this period, the solution

was poured into ice (30 g) and water (50 mL) and the pH was ad-

justed to 4 with hydrochloric acid. The yellow solid was removed

by filtration, taken up in dichloromethane (10 mL) and purified

by thin layer chromatography with dichloromethane as eluent. The

solvent was evaporated to dryness and the residue were recrystal-

lised from ethanol to give the (E,E)-2,3-distyryl-4H-chromen-4-

ones 8a–c.

(E,E)-2,3-Bis(2-phenylvinyl)-4H-chromen-4-one (8a): Yield 0.78 g

1

(53%); m.p. 160–162 °C. H NMR: δ = 7.21 (d, J = 15.8 Hz, 1 H,

αЈ-H), 7.29 (tt, J = 7.2, 1.7 Hz, 1 H, 4Ј-H), 7.33–7.43 (m, 6 H, 6-

H, 3Ј,5Ј,3ЈЈ,4ЈЈ,5ЈЈ-H), 7.37 (d, J = 15.7 Hz, 1 H, α-H), 7.43 (d, J

= 15.8 Hz, 1 H, βЈ-H), 7.50 (d, J = 8.1 Hz, 1 H, 8-H), 7.54–7.59

(m, 4 H, 2Ј,6Ј,2ЈЈ,6ЈЈ-H), 7.65 (dt, J = 8.1, 1.7 Hz, 1 H, 7-H), 7.67

(d, J = 15.7 Hz, 1 H, β-H), 8.22 (dd, J = 7.9, 1.7 Hz, 1 H, 5-

H) ppm. ¹³C NMR: δ = 117.5 (C-8), 118.5 (C-α), 119.0 (C-3), 119.1

(C-αЈ), 123.1 (C-10), 124.7 (C-6), 126.0 (C-5), 126.7 (C-2Ј,6Ј), 127.7

(C-2ЈЈ,6ЈЈ), 127.9 (C-4Ј), 128.6 (C-3Ј,5Ј), 129.0 (C-3ЈЈ,5ЈЈ), 129.7 (C-

4ЈЈ), 133.5 (C-7), 135.5 (C-1ЈЈ), 136.1 (C-βЈ), 137.1 (C-β), 137.5 (C-

1Ј), 154.9 (C-9), 158.0 (C-2), 177.5 (C-4) ppm. EI-MS: m/z (%) =

350 [M]^+·(58), 273 (100), 259 (4), 228 (9), 215 (7), 202 (8), 152 (6),

121 (8), 115 (11), 92 (8), 77 (13), 63 (7), 51 (7). C₂₅H₁₈O₂(350.41):

calcd. for C 85.69, H 5.18; found C 85.44, H 5.34.

Synthesis of the 2-Acetylphenyl (E)-Cinnamates 10a–i. Method 1:

Cinnamoyl chloride (1.9 g, 11.4 mmol) was added to a solution of

the appropriate acetophenone (5.7 mmol) in dry pyridine (150 mL).

The solution was stirred under nitrogen at room temperature for

2 h. After that period, the solution was poured into ice (100 g) and

water (100 mL), and the pH was adjusted to 4 with dilute hydro-

chloric acid. The mixture was vigorously stirred for 15 min, the

precipitate was removed and dissolved in chloroform (100 mL), and

the organic layer was washed with water (3ϫ100 mL). The solvent

was evaporated to dryness, and the residue was purified by silica

gel column chromatography with dichloromethane as eluent. The

solvent was removed to dryness in each case, and the residue was

recrystallised from ethanol to give the desired 2-acetylphenyl (E)-

cinnamate 10a, 10d, 10f or 10h in good yield.

2,3-Diphenyl-1,2-dihydro-9H-xanthen-9-one (9a): Yellowish oil. ¹H

NMR: δ = 3.19 (dd, J = 16.8, 8.4 Hz, 1 H, 1_cis-H), 3.45 (dd, J =

16.8, 2.0 Hz, 1 H, 1_trans-H), 4.33 (brd, J = 8.4 Hz, 1 H, 2-H), 7.02

2-Acetylphenyl (E)-3-Phenylacrylate (10a): This compound showed

spectroscopic and analytical data identical to those previously re-

(s, 1 H, 4-H), 7.15–7.23 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.25–7.27 (m, 2 H, ported.^[32]

2650

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

2-Acetyl-5-methoxyphenyl (E)-3-Phenylacrylate (10d): Yield 1.47 g

(87%); m.p. 97–99 °C. H NMR: δ = 2.53 (s, 3 H, 2-CH₃), 3.86 (s,

3 H, 4Ј-OCH₃), 6.69 (d, J = 16.0 Hz, 1 H, α-H), 6.69 (d, J = 2.5 Hz,

1 H, 3Ј-H), 6.85 (dd, J = 8.8, 2.5 Hz, 1 H, 5Ј-H), 7.42–7.44 (m, 3

1 H, 4Ј-H), 7.85 (dd, J = 7.9, 1.7 Hz, 1 H, 6Ј-H), 7.85 (d, J =

16.0 Hz, 1 H, β-H) ppm. ¹³C NMR: δ = 29.8 (2-CH₃), 55.9 and

56.0 (3ЈЈ,4ЈЈ-OCH₃), 109.6 (C-2ЈЈ), 110.9 (C-5ЈЈ), 114.2 (C-α), 123.3

(C-6ЈЈ), 123.8 (C-3Ј), 126.0 (C-5Ј), 126.9 (C-1ЈЈ), 130.1 (C-6Ј), 131.4

1

H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.59–7.62 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.88 (d, J = 8.8 Hz, (C-1Ј), 133.3 (C-4Ј), 147.3 (C-β), 149.2 (C-2Ј, C-3ЈЈ), 151.6 (C-4ЈЈ),

1 H, 6Ј-H), 7.91 (d, J = 16.0 Hz, 1 H, β-H) ppm. ¹³C NMR: δ =

29.5 (2-CH₃), 55.7 (4Ј-OCH₃), 109.1 (C-3Ј), 111.9 (C-5Ј), 116.8 (C-

α), 123.5 (C-1Ј), 128.4 (C-2ЈЈ.6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ), 130.8 (C-4ЈЈ),

132.3 (C-6Ј), 134.0 (C-1ЈЈ), 147.3 (C-β), 151.4 (C-2Ј), 163.7 (C-4Ј),

165.1 (C=O), 195.8 (C-1) ppm. ESI-MS: m/z (%) = 297 [M + H]⁺

(8), 319 [M + Na]⁺(100), 335 [M + K]⁺(13), 615 [2ϫM + Na]⁺

(43). C₁₈H₁₆O₄(296.32): calcd. for C 72.96, H 5.44; found C 72.84,

H 5.57.

165.5 (C=O), 197.9 (C-1) ppm. ESI-MS: m/z (%) = 349 [M +

Na]⁺(100), 365 [M + K]⁺(17), 675 [2M + Na]⁺(86). C₁₉H₁₈O₅

(326.34): calcd. for C 69.93, H 5.56; found C 69.56, H 5.69.

2-Acetyl-5-methoxyphenyl (E)-2-(3,4-Dimethoxyphenyl)acrylate

1

(10e): Yield 2.05 g (67%); m.p. 142–143 °C. H NMR: δ = 2.53 (s,

3 H, 2-CH₃), 3.87 (s, 3 H, 4Ј-OCH₃), 3.94 (s, 6 H, 3ЈЈ,4ЈЈ-OCH₃),

6.56 (d, J = 15.9 Hz, 1 H, α-H), 6.68 (d, J = 2.5 Hz, 1 H, 3Ј-H),

6.85 (dd, J = 8.8, 2.5 Hz, 1 H, 5Ј-H), 6.90 (d, J = 8.3 Hz, 1 H, 5ЈЈ-

H), 7.13 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.18 (dd, J = 8.3, 1.9 Hz, 1

H, 6ЈЈ-H), 7.85 (d, J = 15.9 Hz, 1 H, β-H), 7.88 (d, J = 8.8 Hz, 1

H, 6Ј-H) ppm. ¹³C NMR: δ = 29.6 (2-CH₃), 55.7 (4Ј-OCH₃), 55.9

and 56.0 (3ЈЈ,4ЈЈ-OCH₃), 109.1 (C-3Ј), 109.7 (C-2ЈЈ), 110.9 (C-5ЈЈ),

111.8 (C-5Ј), 114.4 (C-α), 123.3 (C-6ЈЈ), 123.6 (C-1Ј), 127.0 (C-1ЈЈ),

132.3 (C-6Ј), 147.3 (C-β), 149.2 (C-3ЈЈ), 151.50 and 151.54 (C-2Ј,

C-4ЈЈ), 163.7 (C-4Ј), 165.4 (C=O), 195.9 (C-1) ppm. ESI-MS: m/z

(%) = 379 [M + Na]⁺(92), 395 [M + K]⁺(15), 735 [2M + Na]⁺

(100), 751 [2M + K]⁺(4), 1091 [3M + Na]⁺(4). C₂₀H₂₀O₆(356.37):

calcd. for C 67.41, H 5.66; found C 67.32, H 5.94.

2-Acetyl-3-methoxyphenyl (E)-3-Phenylacrylate (10f): Yield 1.43 g

1

(85%); m.p. 101–102 °C. H NMR: δ = 2.52 (s, 3 H, 2-CH₃), 3.87

(s, 3 H, 6Ј-OCH₃), 6.58 (d, J = 16.0 Hz, 1 H, α-H), 6.81 (dd, J =

8.3, 0.7 Hz, 1 H, 3Ј-H), 6.85 (d, J = 8.3 Hz, 1 H, 5Ј-H), 7.38 (t, J

= 8.3 Hz, 1 H, 4Ј-H), 7.40–7.42 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.55–7.58

(m, 2 H, 2ЈЈ,6ЈЈ-H), 7.83 (d, J = 16.0 Hz, 1 H, β-H) ppm. ¹³C

NMR: δ = 31.7 (2-CH₃), 55.9 (6Ј-OCH₃), 108.6 (C-5Ј), 115.1 (C-

3Ј), 116.6 (C-α), 124.5 (C-1Ј), 128.4 (C-2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ),

130.8 (C-4ЈЈ), 130.9 (C-4Ј), 134.0 (C-1ЈЈ), 147.2 (C-β), 147.6 (C-2Ј),

157.3 (C-6Ј), 165.1 (C=O), 200.7 (C-1) ppm. ESI-MS: m/z (%) =

297 [M + H]⁺(6), 319 [M + Na]⁺(100), 335 [M + K]⁺(16), 615

[2M + Na]⁺(89). C₁₈H₁₆O₄(296.32): calcd. for C 72.96, H 5.44;

found C 73.36, H 5.47.

2-Acetyl-3-methoxyphenyl (E)-2-(3,4-Dimethoxyphenyl)acrylate

1

(10g): Yield 1.96 g (64%); m.p. 86–88 °C. H NMR: δ = 2.52 (s, 3

H, 2-CH₃), 3.88 (s, 3 H, 6Ј-OCH₃), 3.93 and 3.94 (2ϫs, 6 H, 3ЈЈ,4ЈЈ-

OCH₃), 6.45 (d, J = 15.8 Hz, 1 H, α-H), 6.81 (dd, J = 8.3, 0.7 Hz,

1 H, 3Ј-H), 6.85 (d, J = 8.4 Hz, 1 H, 5Ј-H), 6.89 (d, J = 8.3 Hz, 1

H, 5ЈЈ-H), 7.10 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 7.15 (dd, J = 8.3, 2.0 Hz,

1 H, 6ЈЈ-H), 7.38 (dd, J = 8.4, 8.3 Hz, 1 H, 4Ј-H), 7.78 (d, J =

15.8 Hz, 1 H, β-H) ppm. ¹³C NMR: δ = 31.7 (2-CH₃), 55.9 and

56.0 (6Ј,3ЈЈ,4ЈЈ-OCH₃), 108.6 (C-5Ј), 109.6 (C-2ЈЈ), 110.9 (C-5ЈЈ),

114.2 (C-α), 115.2 (C-3Ј), 123.3 (C-6ЈЈ), 124.6 (C-1Ј), 127.0 (C-1ЈЈ),

130.9 (C-4Ј), 147.1 (C-β), 147.7 (C-2Ј), 149.2 (C-3ЈЈ), 151.5 (C-4ЈЈ),

157.3 (C-6Ј), 165.3 (C=O), 200.9 (C-1) ppm. ESI-MS: m/z (%) =

357 [M + H]⁺(15), 379 [M + Na]⁺(53), 395 [M + K]⁺(11), 753

[2M + Na]⁺(31). C₂₀H₂₀O₆(356.37): calcd. for C 67.41, H 5.66;

found C 67.55, H 5.74.

2-Acetyl-3,5-dimethoxyphenyl (E)-3-Phenylacrylate (10h): Yield

1.75 g (94%); m.p. 97–98 °C. H NMR: δ = 2.49 (s, 3 H, 2-CH₃),

1

3.82 (s, 3 H, 4Ј-OCH₃), 3.86 (s, 3 H, 6Ј-OCH₃), 6.31 (d, J = 2.2 Hz,

1 H, 3Ј-H), 6.39 (d, J = 2.2 Hz, 1 H, 5Ј-H), 6.59 (d, J = 16.0 Hz,

1 H, α-H), 7.40–7.42 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.56–7.59 (m, 2 H,

2ЈЈ,6ЈЈ-H), 7.83 (d, J = 16.0 Hz, 1 H, β-H) ppm. ¹³C NMR: δ =

31.9 (2-CH₃), 55.6 (4Ј-OCH₃), 55.9 (6Ј-OCH₃), 96.5 (C-5Ј), 99.9

(C-3Ј), 116.7 (C-α), 117.3 (C-1Ј), 128.4 (C-2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ),

130.7 (C-4ЈЈ), 134.0 (C-1ЈЈ), 147.1 (C-β), 149.5 (C-2Ј), 159.1 (C-6Ј),

162.2 (C-4Ј), 165.2 (C=O), 199.5 (C-1) ppm. ESI-MS: m/z (%) =

327 [M + H]⁺(14), 349 [M + Na]⁺(73), 365 [M + K]⁺(12), 675 [2

M + Na]⁺(100). C₁₉H₁₈O₅(326.34): calcd. for C 69.93, H 5.56;

found C 69.81, H 5.62.

2-Acetyl-3,5-dimethoxyphenyl (E)-2-(3,4-Dimethoxyphenyl)acrylate

Method 2: The appropriate cinnamic acid (16.8 mmol) and phos-

phorus oxychloride (4.2 mL, 45.9 mmol) were added to a solution

of the appropriate acetophenone (8.6 mmol) in dry pyridine

(100 mL). The solution was stirred at 60 °C for 2 h, and after that

the solution was poured into ice (50 g) and water (100 mL) and the

pH was adjusted to 4 with hydrochloric acid. The precipitate was

removed by filtration, the residue was dissolved with chloroform

(100 mL), and the organic layer was washed with water

(3ϫ100 mL). The solvent was evaporated, and the residue was

purified by silica gel column chromatography with light petroleum/

dichloromethane 3:7 as eluent. The solvent was removed to dryness

in each case, and the residue was recrystallised from ethanol to give

the desired 2-acetylphenyl (E)-cinnamates 10b, 10c, 10e, 10g or 10i

in good yield.

1

(10i): Yield 1.66 g (50%); m.p. 140–142 °C. H NMR: δ = 2.49 (s,

3 H, 2-CH₃), 3.82 (s, 3 H, 4Ј-OCH₃), 3.85 (s, 3 H, 6Ј-OCH₃), 3.93

(s, 6 H, 3ЈЈ,4ЈЈ-OCH₃), 6.31 (d, J = 2.2 Hz, 1 H, 3Ј-H), 6.38 (d, J

= 2.2 Hz, 1 H, 5Ј-H), 6.46 (d, J = 15.9 Hz, 1 H, α-H), 6.88 (d, J =

8.3 Hz, 1 H, 5ЈЈ-H), 7.10 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 7.15 (dd, J =

8.3, 2.0 Hz, 1 H, 6ЈЈ-H), 7.78 (d, J = 15.9 Hz, 1 H, β-H) ppm. ¹³C

NMR: δ = 31.8 (2-CH₃), 55.6 (4Ј-OCH₃), 55.8 (3ЈЈ,4ЈЈ-OCH₃), 55.9

(6Ј-OCH₃), 96.4 (C-5Ј), 100.0 (C-3Ј), 109.6 (C-2ЈЈ), 110.9 (C-5ЈЈ),

114.3 (C-α), 117.3 (C-1Ј), 123.2 (C-6ЈЈ), 127.0 (C-1ЈЈ), 147.0 (C-β),

149.1 (C-3ЈЈ), 149.6 (C-2Ј), 151.4 (C-4ЈЈ), 159.0 (C-6Ј), 162.1 (C-

4Ј), 165.4 (C=O), 199.6 (C-1) ppm. ESI-MS: m/z (%) = 387 [M +

H]⁺(6), 409 [M + Na]⁺(89), 425 [M + K]⁺(12), 795 [2M + Na]⁺

(100), 811 [2M + K]⁺(5). C₂₁H₂₂O₇(386.40): calcd. for C 65.28,

H 5.74; found C 65.60, H 5.71.

2-Acetylphenyl (E)-2-(4-Methoxyphenyl)acrylate (10b): This com-

pound showed spectroscopic and analytical data identical to those

previously reported.^[32]

Synthesis of the 5-Aryl-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-

dien-1-ones 11a–i: Potassium hydroxide (powder, 1.4 g, 25 mmol)

was added to a solution of the appropriate 2-acetylphenyl cinna-

mate (10a–i, 5 mmol) in dimethyl sulfoxide (30 mL). The solution

was stirred at room temperature for 2 h. After that period, the solu-

tion was poured into ice (50 g) and water (100 mL), and the pH

was adjusted to 4 with dilute hydrochloric acid. The obtained solid

was removed by filtration, dissolved in chloroform (80 mL) and

washed with water (2ϫ100 mL). The solvent was evaporated to

2-Acetylphenyl (E)-2-(3,4-Dimethoxyphenyl)acrylate (10c): Yield

1

1.96 g (70%); m.p. 97–99 °C. H NMR: δ = 2.58 (s, 3 H, 2-CH₃),

3.94 (s, 6 H, 3ЈЈ,4ЈЈ-OCH₃), 6.55 (d, J = 16.0 Hz, 1 H, α-H), 6.90

(d, J = 8.3 Hz, 1 H, 5ЈЈ-H), 7.13 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.18

(dd, J = 8.3, 1.9 Hz, 1 H, 6ЈЈ-H), 7.19 (dd, J = 7.9, 1.2 Hz, 1 H,

3Ј-H), 7.35 (dt, J = 7.9, 1.2 Hz, 1 H, 5Ј-H), 7.57 (dt, J = 7.9, 1.7 Hz,

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2651

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

dryness in each case, and the residue was recrystallised from etha-

nol to give the expected 5-aryl-3-hydroxy-1-(2-hydroxyphenyl)-2,4-

pentadien-1-one (11a–i) in good yield.

1) ppm. ESI-MS: m/z (%) = 397 [M + H]⁺(22), 319 [M + Na]⁺

(18). C₁₈H₁₆O₄(296.32): calcd. for C 72.96, H 5.44; found C 72.86,

H 5.44.

5-Aryl-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-ones 11a and

11b: These compounds showed spectroscopic and analytical data

identical to those previously reported.^[32]

5-(3,4-Dimethoxyphenyl)-3-hydroxy-1-(2-hydroxy-6-methoxyphenyl)-

penta-2,4-dien-1-one (11g): Yield 1.16 g (65%); m.p. 123–125 °C. ¹H

NMR: δ = 3.929, 3.932 and 3.95 (3ϫs, 9 H, 6Ј,3ЈЈ,4ЈЈ-OCH₃), 6.41

(d, J = 8.2 Hz, 1 H, 5Ј-H), 6.45 (brd, J = 15.0 Hz, 1 H, 4-H), 6.59

(dd, J = 8.3, 0.8 Hz, 1 H, 3Ј-H), 6.77 (s, 1 H, 2-H), 6.88 (d, J =

8.3 Hz, 1 H, 5ЈЈ-H), 7.08 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.15 (dd, J =

8.3, 1.9 Hz, 1 H, 6ЈЈ-H), 7.31 (dd, J = 8.3, 8.2 Hz, 1 H, 4Ј-H), 7.59

(d, J = 15.0 Hz, 1 H, 5-H), 12.76 (s, 1 H, 2Ј-OH), 15.01 (d, J =

1.0 Hz, 1 H 3-OH) ppm. ¹³C NMR: δ = 55.85, 55.91 and 56.0

(6Ј,3ЈЈ,4ЈЈ-OCH₃), 101.6 (C-5Ј), 103.3 (C-2), 109.7 (C-2ЈЈ), 110.6

(C-1Ј), 111.1 (C-3Ј, C-5ЈЈ), 120.6 (C-4), 122.4 (C-6ЈЈ), 128.2 (C-1ЈЈ),

134.9 (C-4Ј), 139.4 (C-5), 149.2 (C-3ЈЈ), 150.9 (C-4ЈЈ), 160.2 (C-6Ј),

164.0 (C-2Ј), 175.0 (C-3), 194.7 (C-1) ppm. ESI-MS: m/z (%) = 357

[M + H]⁺(16), 379 [M + Na]⁺(21). C₂₀H₂₀O₆(356.37): calcd. for

C 67.41, H 5.66; found C 67.29, H. 5.71.

3-Hydroxy-1-(2-hydroxyphenyl)-5-(3,4-dimethoxyphenyl)penta-2,4-

dien-1-one (11c): Yield 1.19 g (73%); m.p. 136–138 °C. ¹H NMR: δ

= 3.93 (s, 3 H, 4ЈЈ-OCH₃), 3.95 (s, 3 H, 3ЈЈ-OCH₃), 6.31 (s, 1 H, 2-

H), 6.47 (brd, J = 15.8 Hz, 1 H, 4-H), 6.89 (ddd, J = 8.3, 8.1,

1.0 Hz, 1 H, 5Ј-H), 6.89 (d, J = 8.3 Hz, 1 H, 5ЈЈ-H), 6.99 (dd, J =

7.7, 1.0 Hz, 1 H, 3Ј-H), 7.08 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.15 (dd,

J = 8.3, 1.9 Hz, 1 H, 6ЈЈ-H), 7.45 (ddd, J = 8.1, 7.7, 1.5 Hz, 1 H,

4Ј-H), 7.61 (d, J = 15.8 Hz, 1 H, 5-H), 7.70 (dd, J = 8.3, 1.5 Hz, 1

H, 6Ј-H), 12.28 (s, 1 H, 2Ј-OH), 14.74 (d, J = 0.8 Hz, 1 H, 3-

OH) ppm. ¹³C NMR: δ = 55.9 (3ЈЈ-OCH₃), 56.0 (4ЈЈ-OCH₃), 96.5

(C-2), 109.5 (C-2ЈЈ), 111.1 (C-5ЈЈ), 118.7 (C-3Ј), 118.9 (C-5Ј), 119.1

(C-1Ј), 119.8 (C-4), 122.6 (C-6ЈЈ), 127.9 (C-1ЈЈ), 128.4 (C-6Ј), 135.6

(C-4Ј), 139.9 (C-5), 149.2 (C-3ЈЈ), 151.1 (C-4ЈЈ), 162.5 (C-2Ј), 175.0

(C-3), 195.6 (C-1) ppm. ESI-MS: m/z (%) = 327 [M + H]⁺(35), 349

[M + Na]⁺(25). C₁₉H₁₈O₅(326.34): calcd. for C 69.93, H 5.56;

found C 69.54, H 5.74%.

3-Hydroxy-1-(2-hydroxy-4,6-dimethoxyphenyl)-5-phenylpenta-2,4-

dien-1-one (11h): Yield 1.30 g (80%); m.p. 127–128 °C. ¹H NMR: δ

= 3.81 (s, 3 H, 4Ј-OCH₃), 3.89 (s, 3 H, 6Ј-OCH₃), 5.95 (d, J =

2.4 Hz, 1 H, 5Ј-H), 6.08 (d, J = 2.4 Hz, 1 H, 3Ј-H), 6.57 (dd, J =

15.9, 1.2 Hz, 1 H, 4-H), 6.75 (s, 1 H, 2-H), 7.34–7.42 (m, 3 H,

3ЈЈ,4ЈЈ,5ЈЈ-H), 7.53–7.56 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.57 (d, J = 15.9 Hz,

1 H, 5-H), 13.62 (s, 1 H, 2Ј-OH), 14.73 (d, J = 1.2 Hz, 1 H, 3-

OH) ppm. ¹³C NMR: δ = 55.5 (4Ј-OCH₃), 55.6 (6Ј-OCH₃), 91.3

(C-5Ј), 94.0 (C-3Ј), 103.0 (C-2), 104.6 (C-1Ј), 123.2 (C-4), 127.8 (C-

2ЈЈ,6ЈЈ), 128.8 (C-3ЈЈ,5ЈЈ), 129.6 (C-4ЈЈ), 135.3 (C-1ЈЈ), 138.3 (C-5),

161.8 (C-6Ј), 165.5 (C-4Ј), 167.2 (C-2Ј), 173.1 (C-3), 193.9 (C-

1) ppm. ESI-MS: m/z (%) = 326 [M + H]⁺(21), 349 [M + Na]⁺

(21), 675 [2M + Na]⁺(6). C₁₉H₁₈O₅(326.34): calcd. for C 69.93,

H 5.56; found C 70.33, H 5.55.

3-Hydroxy-1-(2-hydroxy-4-methoxyphenyl)-5-phenylpenta-2,4-dien-

1-one (11d): Yield 1.20 g (81%); m.p. 125–127 °C. ¹H NMR: δ =

3.82 (s, 3 H, 4Ј-OCH₃), 6.18 (s, 1 H, 2-H), 6.43 (brs, 1 H, 3Ј-H),

6.45 (dd, J = 8.7, 2.5 Hz, 1 H, 5Ј-H), 6.56 (dd, J = 15.9, 0.9 Hz, 1

H, 4-H), 7.35–7.41 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.52–7.55 (m, 2 H,

2ЈЈ,6ЈЈ-H), 7.59 (d, J = 8.7 Hz, 1 H, 6Ј-H), 7.59 (d, J = 15.9 Hz, 1

H, 5-H), 12.70 (s, 1 H, 2Ј-OH), 14.51 (d, J = 0.9 Hz, 1 H, 3-

OH) ppm. ¹³C NMR: δ = 55.5 (4Ј-OCH₃), 96.8 (C-2), 101.2 (C-3Ј),

107.9 (C-5Ј), 112.7 (C-1Ј), 122.3 (C-4), 127.9 (C-2ЈЈ,6ЈЈ), 128.9 (C-

3ЈЈ,5ЈЈ), 129.8 (C-4ЈЈ), 130.1 (C-6Ј), 135.1 (C-1ЈЈ), 139.0 (C-5), 165.4

(C-4Ј), 165.8 (C-2Ј), 173.0 (C-3), 194.6 (C-1) ppm. ESI-MS: m/z

(%) = 297 [M + H]⁺(15), 319 [M + Na]⁺(17). C₁₈H₁₆O₄(296.32):

calcd. for C 72.96, H 5.44; found C 72.74, H 5.47.

5-(3,4-Dimethoxyphenyl)-3-hydroxy-1-(2-hydroxy-4,6-dimethoxy-

phenyl)penta-2,4-dien-1-one (11i): Yield 1.49 g (77%); m.p. 148–

1

150 °C. H NMR: δ = 3.929, 3.932 and 3.95 (3ϫs, 9 H, 6Ј,3ЈЈ,4ЈЈ-

OCH₃), 6.41 (d, J = 8.2 Hz, 1 H, 5Ј-H), 6.45 (d, J = 15.0 Hz, 1 H,

4-H), 6.59 (dd, J = 8.2, 0.8 Hz, 1 H, 3Ј-H), 6.77 (s, 1 H, 2-H), 6.88

(d, J = 8.3 Hz, 1 H, 5ЈЈ-H), 7.08 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.15

(dd, J = 8.3, 1.9 Hz, 1 H, 6ЈЈ-H), 7.31 (t, J = 8.2 Hz, 1 H, 4Ј-H),

7.59 (d, J = 15.0 Hz, 1 H, 5-H), 12.76 (s, 1 H, 2Ј-OH), 15.01 (d, J

= 1.0 Hz, 1 H, 3-OH) ppm. ¹³C NMR: δ = 55.5 (4Ј-OCH₃), 55.6,

55.8 and 55.9 (6Ј,3ЈЈ,4ЈЈ-OCH₃), 91.3 (C-5Ј), 94.0 (C-3Ј), 102.5 (C-

2), 104.6 (C-1Ј), 109.6 (C-2ЈЈ), 111.0 (C-5ЈЈ), 120.9 (C-4), 122.2 (C-

6ЈЈ), 128.3 (C-1ЈЈ), 138.5 (C-5), 149.1 (C-3ЈЈ), 150.6 (C-4ЈЈ), 161.8

(C-6Ј), 165.4 (C-4Ј), 167.1 (C-2Ј), 173.7 (C-3), 193.6 (C-1) ppm.

ESI-MS: m/z (%) = 387 [M + H]⁺(29), 409 [M + Na]⁺(38), 795

[2M + Na]⁺(11). C₂₁H₂₂O₇(386.40): calcd. for C 65.28, H 5.74;

found C 65.56, H 5.83.

5-(3,4-Dimethoxyphenyl)-3-hydroxy-1-(2-hydroxy-4-methoxyphenyl)-

penta-2,4-dien-1-one (11e): Yield 1.21 g (68%); m.p. 149–151 °C. ¹H

NMR: δ = 3.84 (s, 3 H, 4Ј-OCH₃), 3.93 (s, 3 H, 4ЈЈ-OCH₃), 3.95

(s, 3 H, 3ЈЈ-OCH₃), 6.18 (s, 1 H, 2-H), 6.44 (brs, 1 H, 3Ј-H), 6.45

(dd, J = 15.4, 1.0 Hz, 1 H, 4-H), 6.44–6.47 (m, 1 H, 5Ј-H), 6.89 (d,

J = 8.3 Hz, 1 H, 5ЈЈ-H), 7.07 (d, J = 1.9 Hz, 1 H, 2ЈЈ-H), 7.14 (dd,

J = 8.3, 1.9 Hz, 1 H, 6ЈЈ-H), 7.56 (d, J = 15.4 Hz, 1 H, 5-H), 7.59–

7.62 (m, 1 H, 6Ј-H), 12.74 (s, 1 H, 2Ј-OH), 14.59 (d, J = 1.0 Hz, 1

H, 3-OH) ppm. ¹³C NMR: δ = 55.5 (4Ј-OCH₃), 55.9 (3ЈЈ-OCH₃),

56.0 (4ЈЈ-OCH₃), 96.2 (C-2), 101.2 (C-3Ј), 107.8 (C-5Ј), 109.5 (C-

2ЈЈ), 111.1 (C-5ЈЈ), 112.7 (C-1Ј), 120.1 (C-4), 122.4 (C-6ЈЈ), 128.1

(C-1ЈЈ), 130.0 (C-6Ј), 139.1 (C-5), 149.2 (C-3ЈЈ), 150.8 (C-4ЈЈ), 165.3

(C-2Ј), 165.7 (C-4Ј), 173.6 (C-3), 194.3 (C-1) ppm. ESI-MS: m/z

(%) = 357 [M + H]⁺(18), 379 [M + Na]⁺(27), 735 [2M + Na]⁺

(7). C₂₀H₂₀O₆(356.37): calcd. for C 67.41, H 5.66; found C 67.85,

H 5.78.

Synthesis of the 3-Bromo-2-styryl-4H-chromen-4-ones 3a and 3d–k:

Phenyltrimethylammonium tribromide (PTT, 2.1 g, 5.5 mmol) was

added to a THF (60 mL) solution of the appropriate 5-aryl-3-hy-

droxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (11a–i, 5 mmol).

The reaction mixture was stirred and allowed to stand at room

3-Hydroxy-1-(2-hydroxy-6-methoxyphenyl)-5-phenylpenta-2,4-dien-

1-one (11f): Yield 1.38 g (93%); m.p. 123–125 °C. ¹H NMR: δ =

3.93 (s, 3 H, 6Ј-OCH₃), 6.42 (dd, J = 8.2, 0.7 Hz, 1 H, 5Ј-H), 6.59 temperature for 12 h. After that period, the solution was poured

(dd, J = 15.8, 1.1 Hz, 1 H, 4-H), 6.60 (dd, J = 8.4, 0.7 Hz, 1 H, 3Ј- into ice (50 g) and water (80 mL) and stirred for 20 min, and the

H), 6.80 (s, 1 H, 2-H), 7.32 (dd, J = 8.4, 8.2 Hz, 1 H, 4Ј-H), 7.36– obtained yellow solid was removed by filtration. The residue was

7.42 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.55–7.58 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.63 (d, taken up in chloroform (50 mL) and washed with water

J = 15.8 Hz, 1 H, 5-H), 12.73 (s, 1 H, 2Ј-OH), 14.88 (d, J = 1.1 Hz,

(3ϫ50 mL). The solvent was removed to dryness and the residue

1 H, 3-OH) ppm. ¹³C NMR: δ = 55.8 (6Ј-OCH₃), 101.7 (C-5Ј), was purified by silica gel column chromatography with dichloro-

103.8 (C-2), 110.6 (C-1Ј), 111.1 (C-3Ј), 122.9 (C-4), 127.9 (C- methane as eluent. The obtained residue was recrystallised from

2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ), 129.9 (C-4ЈЈ), 135.1 (C-4Ј), 135.2 (C-1ЈЈ), ethanol to give the 3-bromo-2-styryl-4H-chromen-4-one (3a or 3d–

139.2 (C-5), 160.3 (C-6Ј), 164.1 (C-2Ј), 174.3 (C-3), 195.2 (C- k).

2652

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

(E)-3-Bromo-2-[2-(4-methoxyphenyl)vinyl]-4H-chromen-4-one (3d):

Yield 0.95 g (53%); m.p. 149–151 °C. H NMR: δ = 3.86 (s, 3 H,

(E)-3-Bromo-2-[2-(3,4-dimethoxyphenyl)vinyl]-5-methoxy-4H-

chromen-4-one (3i): Yield 1.21 g (58%); m.p. 190–192 °C. ¹H NMR:

δ = 3.94 (s, 3 H, 4Ј-OCH₃), 3.977 (s, 3 H, 3Ј-OCH₃), 3.982 (s, 3 H,

5-OCH₃), 6.82 (d, J = 8.2 Hz, 1 H, 6-H), 6.91 (d, J = 8.3 Hz, 1 H,

5Ј-H), 7.10 (d, J = 8.4 Hz, 1 H, 8-H), 7.13 (d, J = 1.7 Hz, 1 H, 2Ј-

H), 7.22 (dd, J = 8.3, 1.7 Hz, 1 H, 6Ј-H), 7.27 (d, J = 15.8 Hz, 1 H,

α-H), 7.576 (dd, J = 8.4, 8.2 Hz, 1 H, 7-H), 7.578 (d, J = 15.8 Hz, 1

H, β-H) ppm. ¹³C NMR: δ = 56.0 (4Ј-OCH₃), 56.3 and 56.5 (5,3Ј-

1

4Ј-OCH₃), 6.94 (d, J = 8.8 Hz, 2 H, 3Ј,5Ј-H), 7.33 (d, J = 15.9 Hz,

1 H, α-H), 7.40 (ddd, J = 8.5, 8.4, 0.7 Hz, 1 H, 6-H), 7.52 (d, J =

8.0 Hz, 1 H, 8-H), 7.59 (d, J = 8.8 Hz, 2 H, 2Ј,6Ј-H), 7.66 (d, J =

15.9 Hz, 1 H, β-H), 7.69 (ddd, J = 8.4, 8.0, 1.6 Hz, 1 H, 7-H), 8.22

(dd, J = 8.5, 1.6 Hz, 1 H, 5-H) ppm. ¹³C NMR: δ = 55.4 (4Ј-

OCH₃), 108.9 (C-3), 114.5 (C-3Ј,5Ј), 116.7 (C-α), 117.4 (C-8), 122.0

(C-10), 125.2 (C-6), 126.3 (C-5), 127.6 (C-1Ј), 129.8 (C-2Ј,6Ј), 133.9 OCH₃), 106.5 (C-6), 109.4 (C-8), 109.6 (C-2Ј), 110.6 (C-3), 111.1

(C-7), 139.3 (C-β), 154.8 (C-9), 158.8 (C-2), 161.4 (C-4Ј), 172.7 (C- (C-5Ј), 112.8 (C-10), 116.9 (C-α), 122.4 (C-6Ј), 128.1 (C-1Ј), 133.9

4) ppm. ESI-MS: m/z (%) = 357 [M + H]⁺(⁷⁹Br, 65), 359 [M + H]

(C-7), 138.8 (C-β), 149.3 (C-3Ј), 151.0 (C-4Ј), 156.8 (C-9), 156.9 (C-

2), 159.7 (C-5), 171.8 (C-4) ppm. ESI-MS: m/z (%) = 417 [M +

H]⁺(⁷⁹Br, 26), 419 [M + H]⁺(⁸¹Br, 25), 439 [M + Na]⁺(⁷⁹Br, 13),

441 [M + Na]⁺(⁸¹Br, 13), 855 [2M + Na]⁺(⁷⁹Br, 15), 857 [2M +

Na]⁺(⁸¹Br, 30). C₂₀H₁₇BrO₅(417.25): calcd. for C 57.57, H 4.11;

found C 57.27, H 4.21.

+

(⁸¹Br, 66), 379 [M + Na]⁺(⁷⁹Br, 29), 381 [M + Na]⁺(⁸¹Br, 89),

735 [2M + Na]⁺(⁷⁹Br, 19), 737 [2M + Na]⁺(⁸¹Br, 40). C₁₈H₁₃BrO₃

(357.20): calcd. for C 60.52, H 3.67; found C 60.14, H 3.66.

(E)-3-Bromo-2-[2-(3,4-dimethoxyphenyl)vinyl]-4H-chromen-4-one

(3e): This compound showed spectroscopic and analytical data

identical to those previously reported.^[27]

(E)-3-Bromo-5,7-dimethoxy-2-(2-phenylvinyl)-4H-chromen-4-one

(3j): Yield 0.95 g (49%); m.p. 181–183 °C. ¹H NMR: δ = 3.928 and

3.931 (2ϫs, 6 H, 5,7-OCH₃), 6.36 (d, J = 2.3 Hz, 1 H, 6-H), 6.53

(d, J = 2.3 Hz, 1 H, 8-H), 7.40 (d, J = 16.0 Hz, 1 H, α-H), 7.41–

7.44 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.59 (d, J = 16.0 Hz, 1 H, β-H), 7.61–

7.64 (m, 2 H, 2Ј,6Ј-H) ppm. ¹³C NMR: δ = 55.8 and 56.4 (5,7-

OCH₃), 92.2 (C-8), 96.3 (C-6), 107.6 (C-10), 111.6 (C-3), 119.2 (C-

α), 127.9 (C-2Ј,6Ј), 129.0 (C-3Ј,5Ј), 130.0 (C-4Ј), 135.1 (C-1Ј), 138.2

(C-β), 156.1 (C-2), 158.4 (C-9), 160.9 (C-5), 164.3 (C-7), 171.0 (C-

4) ppm. ESI-MS: m/z = 387 [M + H]⁺(⁷⁹Br, 33), 389 [M + H]⁺

(⁸¹Br, 33), 409 [M + Na]⁺(⁷⁹Br, 8), 411 [M + Na]⁺(⁸¹Br, 8), 795

[2M + Na]⁺(⁷⁹Br, 18), 797 [2M + Na]⁺(⁸¹Br, 35). C₁₉H₁₅BrO₄

(387.22): calcd. for C 58.93, H 3.90; found C 58.77, H 4.07.

(E)-3-Bromo-7-methoxy-2-(2-phenylvinyl)-4H-chromen-4-one (3f):

1

Yield 1.73 g (97%); m.p. 174–176 °C. H NMR: δ = 3.95 (s, 3 H,

7-OCH₃), 6.93 (d, J = 2.4 Hz, 1 H, 8-H), 6.97 (dd, J = 8.8, 2.4 Hz,

1 H, 6-H), 7.40–7.45 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.46 (d, J = 16.0 Hz, 1

H, α-H), 7.63–7.66 (m, 2 H, 2Ј,6Ј-H), 7.67 (d, J = 16.0 Hz, 1 H, β-

H), 8.13 (d, J = 8.8 Hz, 1 H, 5-H) ppm. ¹³C NMR: δ = 55.9 (7-

OCH₃), 99.7 (C-8), 109.9 (C-3), 114.7 (C-6), 115.9 (C-10), 119.3

(C-α), 127.7 (C-5), 128.0 (C-2Ј,6Ј), 129.0 (C-3Ј,5Ј), 130.2 (C-4Ј),

135.0 (C-1Ј), 138.9 (C-β), 156.6 (C-9), 157.9 (C-2), 164.4 (C-7),

172.1 (C-4) ppm. ESI-MS: m/z (%) = 357 [M + H]⁺(⁷⁹Br, 97), 359

[M + H]⁺(⁸¹Br, 96), 379 [M + Na]⁺(⁷⁹Br, 39), 381 [M + Na]⁺

(⁸¹Br, 83), 395 [M + K]⁺(⁷⁹Br, 10), 397 [M + K]⁺(⁸¹Br, 13), 735

[2M + Na]⁺(⁷⁹Br, 50), 737 [2M + Na]⁺(⁸¹Br, 98). C₁₈H₁₃BrO₃

(357.20): calcd. for C 60.52, H 3.67; found C 60.43, H 4.12.

(E)-3-Bromo-2-[2-(3,4-dimethoxyphenyl)vinyl]-5,7-dimethoxy-4H-

chromen-4-one (3k): Yield 0.67 g (30 %); m.p. 208–210 °C. ¹H

NMR: δ = 3.91 (s, 3 H, 5-OCH₃), 3.92 (s, 3 H, 7-OCH₃), 3.94 (s,

3 H, 4Ј-OCH₃), 3.96 (s, 3 H, 3Ј-OCH₃), 6.33 (d, J = 2.3 Hz, 1 H,

6-H), 6.50 (d, J = 2.3 Hz, 1 H, 8-H), 6.90 (d, J = 8.5 Hz, 1 H, 5Ј-

H), 7.10 (d, J = 1.9 Hz, 1 H, 2Ј-H), 7.19 (dd, J = 8.5, 1.9 Hz, 1 H,

6Ј-H), 7.20 (d, J = 15.9 Hz, 1 H, α-H), 7.50 (d, J = 15.9 Hz, 1 H,

β-H) ppm. ¹³C NMR: δ = 55.8 (7-OCH₃), 55.9 (3Ј-OCH₃), 56.0 (4Ј-

OCH₃), 56.3 (5-OCH₃), 92.1 (C-8), 96.2 (C-6), 107.5 (C-10), 109.6

(C-2Ј), 110.8 (C-3), 111.1 (C-5Ј), 116.9 (C-α), 122.2 (C-6Ј), 128.1

(C-1Ј), 138.1 (C-β), 149.2 (C-3Ј), 150.9 (C-4Ј), 156.4 (C-2), 158.4

(C-9), 160.8 (C-5), 164.2 (C-7), 170.9 (C-4) ppm. ESI-MS: m/z (%)

= 447 [M + H]⁺(⁷⁹Br, 46), 449 [M + H]⁺(⁸¹Br, 21), 469 [M +

Na]⁺(⁷⁹Br, 16), 471 [M + Na]⁺(⁸¹Br, 16), 915 [2M + Na]⁺(⁷⁹Br,

19), 917 [2M + Na]⁺(⁸¹Br, 38). C₂₁H₁₉BrO₆(447.28): calcd. for C

56.39, H 4.28; found C 56.27, H 4.36.

(E)-3-Bromo-2-[2-(3,4-dimethoxyphenyl)vinyl]-7-methoxy-4H-

chromen-4-one (3g): Yield 1.25 g (60 %); m.p. 195–917 °C. ¹H

NMR: δ = 3.937 and 3.943 (2ϫs, 6 H, 7,4Ј-OCH₃), 3.97 (s, 3 H,

3Ј-OCH₃), 6.90 (d, J = 2.3 Hz, 1 H, 8-H), 6.91 (d, J = 8.3 Hz, 1

H, 5Ј-H), 6.95 (dd, J = 8.8, 2.3 Hz, 1 H, 6-H), 7.12 (d, J = 1.9 Hz,

1 H, 2Ј-H), 7.21 (dd, J = 8.3, 1.9 Hz, 1 H, 6Ј-H), 7.28 (d, J =

15.9 Hz, 1 H, α-H), 7.60 (d, J = 15.9 Hz, 1 H, β-H), 8.11 (d, J =

8.8 Hz, 1 H, 5-H) ppm. ¹³C NMR: δ = 55.86, 55.92 and 56.0

(7,3Ј,4Ј-OCH₃), 99.7 (C-8), 109.1 (C-3), 109.6 (C-2Ј), 111.1 (C-5Ј),

114.5 (C-6), 115.9 (C-10), 116.9 (C-α), 122.4 (C-6Ј), 127.7 (C-5),

128.0 (C-1Ј), 138.9 (C-β), 149.3 (C-3Ј), 151.1 (C-4Ј), 156.5 (C-9),

158.3 (C-2), 164.3 (C-7), 172.0 (C-4) ppm. ESI-MS: m/z (%) = 417

[M + H]⁺(⁷⁹Br, 34), 419 [M + H]⁺(⁸¹Br, 33), 439 [M + Na]⁺(⁷⁹Br,

13), 441 [M + Na]⁺(⁸¹Br, 13), 855 [2M + Na]⁺(⁷⁹Br, 13), 857 [2M

+ Na]⁺(⁸¹Br, 25). C₂₀H₁₇BrO₅(417.25): calcd. for C 57.57, H 4.11;

found C 57.76, H 4.18.

Synthesis of the Methoxylated 2,3-Diaryl-9H-xanthen-9-ones 5g–s:

The appropriate styrene (4a–c, 1.6 mmol for styrene 4a and

0.8 mmol for styrenes 4b and 4c) was added to a mixture of the

appropriate 3-bromo-2-styryl-4H-chromen-4-one (3d–k, 0.4 mmol),

triphenylphosphane (10.5 mg, 0.04 mmol), tetrakis(triphenylphos-

(E)-3-Bromo-5-methoxy-2-(2-phenylvinyl)-4H-chromen-4-one (3h):

1

Yield 1.50 g (84%); m.p. 172–173 °C. H NMR: δ = 3.97 (s, 3 H,

5-OCH₃), 6.82 (dd, J = 8.4, 0.9 Hz, 1 H, 6-H), 7.10 (dd, J = 8.4,

0.9 Hz, 1 H, 8-H), 7.42 (d, J = 16.0 Hz, 1 H, α-H), 7.40–7.45 (m, phane)palladium(0) (23.1 mg, 0.02 mmol) and triethylamine

3 H, 3Ј,4Ј,5Ј-H), 7.58 (t, J = 8.4 Hz, 1 H, 7-H), 7.63 (d, J = 16.0 Hz, (55.8 µL, 0.4 mmol) in N-methyl-2-pyrrolidin-1-one (6 mL). The

1 H, β-H), 7.62–7.64 (m, 2 H, 2Ј,6Ј-H) ppm. ¹³C NMR: δ = 56.4 mixture was stirred under different time and temperature condi-

(5-OCH₃), 106.5 (C-6), 109.4 (C-8), 111.4 (C-3), 112.7 (C-10), 119.1

(C-α), 127.9 (C-2Ј,6Ј), 129.0 (C-3Ј,5Ј), 130.1 (C-4Ј), 134.1 (C-7),

134.9 (C-1Ј), 138.8 (C-β), 156.5 (C-9), 156.8 (C-2), 159.7 (C-5),

171.7 (C-4) ppm. ESI-MS: m/z (%) = 357 [M + H]⁺(⁷⁹Br, 83), 359

[M + H]⁺(⁸¹Br, 80), 379 [M + Na]⁺(⁷⁹Br, 28), 381 [M + Na]⁺

(⁸¹Br, 28), 735 [2M + Na]⁺(⁷⁹Br, 51), 737 [2M + Na]⁺(⁸¹Br, 100),

tions according to the substitution of the compounds (Table 3).

The mixture was then poured into water (20 mL) and ice (10 g) and

extracted with diethyl ether (4ϫ25 mL) and dried with anhydrous

sodium sulfate. The solvent was removed to dryness and the residue

was taken up in dichloromethane (5 mL) and purified by thin layer

chromatography (eluent: dichloromethane/light petroleum 7:3).

The major spot with higher R_fvalue corresponds to the meth-

oxylated 2,3-diaryl-9H-xanthen-9-one (5g–s) and the minor spot

with lower R_fcorresponds to the 2,3-diaryl-3,4-dihydro-9H-

1091 [3 M + Na]^{+ 79}Br, 4), 1093 [3 M + Na]^{+ 8 1}Br, 11).

( (

C₁₈H₁₃BrO₃(357.20): calcd. for C 60.52, H 3.67; found C 60.77, H

3.69.

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2653

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

xanthen-9-one (6g–s). In the cases of the (E)-3-bromo-5-methoxy-

2-styryl-4H-chromen-4-ones 5n–s, it was also possible to isolate the

6,7-diaryl-1-hydroxy-9H-xanthen-9-ones 12n–s. The obtained

methoxylated 2,3-diaryl-9H-xanthen-9-ones were recrystallised

from ethanol and obtained in moderate to good yields (Table 3).

4), 40.9 (C-3), 55.1 (4ЈЈ-OCH₃), 55.3 (4Ј-OCH₃), 113.8 (C-3Ј,5Ј),

114.2 (C-3ЈЈ,5ЈЈ), 114.6 (C-1), 117.0 (C-9a), 118.0 (C-5), 123.9 (C-

8a), 125.0 (C-7), 126.2 (C-8), 126.9 (C-2Ј,6Ј), 128.4 (C-2ЈЈ,6ЈЈ),

131.6 (C-1Ј), 132.7 (C-1ЈЈ), 132.9 (C-6), 135.3 (C-2), 155.9 (C-4b),

158.6 (C-4ЈЈ), 159.1 (C-4Ј), 162.1 (C-4a), 174.2 (C-9) ppm. EI-MS:

m/z (%) = 410 [M]^+·(21), 409 (24), 408 (100), 393 (11), 377 (13),

365 (6), 350 (8), 321 (6), 303 (11), 121 (6). HRMS (EI): calcd. for

C₂₇H₂₂O₄[M]^+·410.1518; found 410.1526.

3-(4-Methoxyphenyl)-2-phenyl-9H-xanthen-9-one (5g): M.p. 150–

153 °C. ¹H NMR: δ = 3.80 (s, 3 H, 4ЈЈ-OCH₃), 6.80 (d, J = 8.8 Hz,

2 H, 3ЈЈ,5ЈЈ-H), 7.13 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.17–7.20 (m,

2 H, 2Ј,6Ј-H), 7.23–7.27 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.39 (ddd, J = 7.7, 2-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-9H-xanthen-9-one

1

7.6, 0.9 Hz, 1 H, 7-H), 7.51 (d, J = 8.5 Hz, 1 H, 5-H), 7.53 (s, 1 H, (5i): M.p. 155–156 °C. H NMR: δ = 3.63 (s, 3 H, 4Ј-OCH₃), 3.81

4-H), 7.73 (ddd, J = 8.5, 7.6, 1.7 Hz, 1 H, 6-H), 8.34 (s, 1 H, 1-H),

8.37 (dd, J = 7.7, 1.7 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 55.2 (4ЈЈ- H, 2Ј-H), 6.83 (d, J = 8.6 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.79–6.85 (m, 2 H,

OCH₃), 113.6 (C-3ЈЈ,5ЈЈ), 118.0 (C-5), 119.2 (C-4), 120.4 (C-9a), 5Ј,6Ј-H), 7.15 (d, J = 8.6 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.41 (ddd, J = 8.0,

(s, 3 H, 4ЈЈ-OCH₃), 3.89 (s, 3 H, 3Ј-OCH₃), 6.60 (d, J = 1.7 Hz, 1

122.0 (C-8a), 123.9 (C-7), 126.7 (C-8), 126.8 (C-4Ј), 128.1 (C-3Ј,5Ј), 7.7, 1.1 Hz, 1 H, 7-H), 7.52 (d, J = 8.0 Hz, 1 H, 5-H), 7.53 (s, 1 H,

128.4 (C-1), 129.9 (C-2Ј,6Ј), 130.8 (C-2ЈЈ,6ЈЈ), 132.1 (C-1ЈЈ), 134.7 4-H), 7.75 (ddd, J = 8.0, 7.7, 1.7 Hz, 1 H, 6-H), 8.36 (s, 1 H, 1-H),

(C-6), 137.0 (C-2), 140.1 (C-1Ј), 147.3 (C-3), 155.3 (C-4a), 156.3 8.38 (dd, J = 8.0, 1.7 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 55.3 (4ЈЈ-

(C-4b), 159.1 (C-4ЈЈ), 177.0 (C-9) ppm. EI-MS: m/z (%) = 378

[M]^+·(100), 377 (23), 363 (10), 347 (23), 335 (11), 334 (13), 305

(10), 276 (6). C₂₆H₁₈O₃(378.42): calcd. for C 82.52, H 4.79; found

C 82.24, H 5.03.

OCH₃), 55.6 (4Ј-OCH₃), 55.8 (3Ј-OCH₃), 110.8 (C-5Ј), 113.3 (C-

2Ј), 113.6 (C-3ЈЈ,5ЈЈ), 118.0 (C-5), 119.2 (C-4), 120.4 (C-9a), 121.9

(C-8a), 122.2 (C-6Ј), 123.9 (C-7), 126.8 (C-8), 127.9 (C-1), 130.7

(C-2ЈЈ,6ЈЈ), 132.4 (C-1ЈЈ), 132.6 (C-1Ј), 134.7 (C-6), 136.7 (C-2),

147.3 (C-3), 147.9 and 148.2 (C-3Ј, C-4Ј), 155.1 (C-4a), 156.3 (C-

4b), 159.1 (C-4ЈЈ), 177.0 (C-9) ppm. EI-MS: m/z (%) = 438 [M]^+·

(100), 423 (8), 407 (9). C₂₈H₂₂O₅(438.47): calcd. for C 76.70, H

5.06; found C 76.47, H 4.93.

3-(4-Methoxyphenyl)-2-phenyl-3,4-dihydro-9H-xanthen-9-one (6g):

1

Yellowish oil. H NMR: δ = 2.96 (dd, J = 17.3, 1.3 Hz, 1 H, 4_trans

-

H), 3.61 (dd, J = 17.3, 8.8 Hz, 1 H, 4_cis-H), 3.70 (s, 3 H, 4ЈЈ-OCH₃),

4.25 (dd, J = 8.8, 1.3 Hz, 1 H, 3-H), 6.76 (d, J = 8.7 Hz, 2 H,

3ЈЈ,5ЈЈ-H), 7.21 (d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.23–7.29 (m, 3 H, 2-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-3,4-dihydro-9H-

1

3Ј,4Ј,5Ј-H), 7.33 (d, J = 8.5 Hz, 1 H, 5-H), 7.36 (ddd, J = 8.2, 7.9,

xanthen-9-one (6i): Yellowish oil. H NMR: δ = 2.96 (dd, J = 17.3,

1.0 Hz, 1 H, 7-H), 7.46–7.49 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.54 (s, 1 H, 1- 1.6 Hz, 1 H, 4_trans-H), 3.62 (dd, J = 17.3, 8.8 Hz, 1 H, 4_cis-H), 3.71

H), 7.58 (ddd, J = 8.5, 8.2, 1.6 Hz, 1 H, 6-H), 8.27 (dd, J = 7.9,

1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 36.8 (C-4), 40.8 (C-3), 55.1

(s, 3 H, 4ЈЈ-OCH₃), 3.84 and 3.86 (2ϫs, 6 H, 3Ј,4Ј-OCH₃), 4.24

(brd, J = 8.8 Hz, 1 H, 3-H), 6.75 (d, J = 8.5 Hz, 1 H, 5Ј-H), 6.77

(4ЈЈ-OCH₃), 114.2 (C-3ЈЈ,5ЈЈ), 116.4 (C-1), 116.8 (C-9a), 118.0 (C- (d, J = 8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.97 (dd, J = 8.5, 2.2 Hz, 1 H, 6Ј-

5), 123.8 (C-8a), 125.0 (C-7), 125.6 (C-2Ј,6Ј), 126.1 (C-8), 127.5 (C- H), 7.10 (d, J = 2.2 Hz, 1 H, 2Ј-H), 7.21 (d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-

4Ј), 128.3 (C-2ЈЈ,6ЈЈ), 128.4 (C-3Ј,5Ј), 132.5 (C-1ЈЈ), 133.0 (C-6), H), 7.35 (dd, J = 8.3, 1.0 Hz, 1 H, 5-H), 7.38 (ddd, J = 7.8, 7.7,

135.6 (C-2), 139.0 (C-1Ј), 155.8 (C-4b), 158.6 (C-4ЈЈ), 162.6 (C-4a), 1.0 Hz, 1 H, 7-H), 7.44 (s, 1 H, 1-H), 7.59 (ddd, J = 8.3, 7.7, 1.7 Hz,

174.2 (C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(14), 379 (29), 378 1 H, 6-H), 8.29 (dd, J = 7.8, 1.7 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ

(100), 377 (30), 363 (16), 347 (24), 335 (13), 334 (14), 333 (11), 305

(11), 276 (8), 215 (6), 135 (7), 105 (5). HRMS (EI): calcd. for

C₂₆H₁₈O₃[M]^+·378.1256; found 378.1244.

= 36.7 (C-4), 41.1 (C-3), 55.1 (4ЈЈ-OCH₃), 55.81 and 55.82 (3Ј,4Ј-

OCH₃), 108.7 (C-2Ј), 110.8 (C-5Ј), 114.2 (C-3ЈЈ,5ЈЈ), 114.8 (C-1),

116.9 (C-9a), 118.0 (C-5), 118.2 (C-6Ј), 123.8 (C-8a), 125.0 (C-7),

126.1 (C-8), 128.3 (C-2ЈЈ,6ЈЈ), 132.0 (C-1Ј), 132.8 (C-1ЈЈ), 132.9 (C-

6), 135.5 (C-2), 148.7 and 148.8 (C-3Ј, C-4Ј), 155.8 (C-4b), 158.6

(C-4ЈЈ), 162.2 (C-4a), 174.2 (C-9) ppm. EI-MS: m/z (%) = 440

[M]^+·(100), 439 (29), 438 (53), 423 (11), 391 (8), 333 (10), 303 (13),

165 (47), 151 (14), 121 (8), 86 (8), 84 (13). HRMS (EI): calcd. for

C₂₈H₂₄O₅[M]^+·440.1624; found 440.1623.

2,3-Bis(4-methoxyphenyl)-9H-xanthen-9-one (5h): M.p. 164–166 °C.

¹H NMR: δ = 3.807 and 3.813 (s, 6 H, 4Ј,4ЈЈ-OCH₃), 6.80 (d, J =

8.8 Hz, 2 H, 3Ј,5Ј-H), 6.82 (d, J = 8.8 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.11 (d,

J = 8.8 Hz, 2 H, 2Ј,6Ј-H), 7.14 (d, J = 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.40

(ddd, J = 7.8, 7.6, 1.0 Hz, 1 H, 7-H), 7.52 (d, J = 7.8 Hz, 1 H, 5-

H), 7.52 (s, 1 H, 4-H), 7.74 (ddd, J = 7.8, 7.6, 1.7 Hz 1 H, 6-H),

8.32 (s, 1 H, 1-H), 8.37 (dd, J = 7.8, 1.7 Hz, 1 H, 8-H) ppm. ¹³C 3-(3,4-Dimethoxyphenyl)-2-phenyl-9H-xanthen-9-one (5j): M.p.

NMR: δ = 55.19 and 55.21 (4Ј,4ЈЈ-OCH₃), 113.5 and 113.6 (C-

1

212–214 °C. H NMR: δ = 3.52 (s, 3 H, 3ЈЈ-OCH₃), 3.89 (s, 3 H,

3Ј,5Ј, C-3ЈЈ,5ЈЈ), 118.0 (C-5), 119.2 (C-4), 120.4 (C-9a), 122.0 (C- 4ЈЈ-OCH₃), 6.56 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 6.83 (d, J = 8.3 Hz, 1

8a), 123.9 (C-7), 126.8 (C-8), 128.1 (C-1), 130.8 and 131.0 (C-2Ј,6Ј, H, 5ЈЈ-H), 6.92 (dd, J = 8.3, 2.0 Hz, 1 H, 6ЈЈ-H), 7.18–7.21 (m, 2

C-2ЈЈ,6ЈЈ), 132.35 and 132.43 (C-1Ј, C-1ЈЈ), 134.7 (C-6), 136.6 (C- H, 2Ј,6Ј-H), 7.24–7.28 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.40 (ddd, J = 7.8, 7.6,

2), 147.3 (C-3), 155.1 (C-4a), 156.3 (C-4b), 158.5 (C-4Ј), 159.1 (C-

4ЈЈ), 177.0 (C-9) ppm. EI-MS: m/z (%) = 408 [M]^+·(100), 407 (8),

393 (14), 377 (19), 365 (8), 350 (12), 334 (6), 333 (6), 321 (10).

C₂₇H₂₀O₄(408.45): calcd. for C 79.40, H 4.94; found C 79.12, H

5.03.

1.0 Hz, 1 H, 7-H), 7.52 (d, J = 8.0 Hz, 1 H, 5-H), 7.58 (s, 1 H, 4-

H), 7.74 (ddd, J = 8.0, 7.6, 1.7 Hz, 1 H, 6-H), 8.35 (s, 1 H, 1-H),

8.37 (dd, J = 7.8, 1.7 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 55.5 (3ЈЈ-

OCH₃), 55.8 (4ЈЈ-OCH₃), 110.7 (C-5ЈЈ), 113.3 (C-2ЈЈ), 117.9 (C-5),

119.0 (C-4), 120.4 (C-9a), 121.89 (C-6ЈЈ), 121.93 (C-8a), 123.9 (C-

7), 126.7 (C-8), 126.8 (C-4Ј), 128.1 (C-3Ј,5Ј), 128.3 (C-1), 129.8 (C-

2Ј,6Ј), 132.2 (C-1ЈЈ), 134.7 (C-6), 137.0 (C-2), 140.2 (C-1Ј), 147.2

(C-3), 148.1 and 148.6 (C-3ЈЈ, C-4ЈЈ), 155.3 (C-4a), 156.2 (C-4b),

176.9 (C-9) ppm. EI-MS: m/z (%) = 408 [M]^+·(100), 393 (15), 377

814, 361 (13), 350 (10), 333 (15), 321 (10), 305 (8), 292 (6).

C₂₇H₂₀O₄(408.45): calcd. for C 79.40, H 4.94; found C 79.07, H

4.91.

2,3-Bis(4-methoxyphenyl)-3,4-dihydro-9H-xanthen-9-one (6h): Yel-

lowish oil. ¹H NMR: δ = 2.96 (dd, J = 17.3, 1.5 Hz, 1 H, 4_trans-H),

3.62 (dd, J = 17.3, 8.3 Hz, 1 H, 4_cis-H), 3.72 (s, 3 H, 4ЈЈ-OCH₃),

3.79 (s, 3 H, 4Ј-OCH₃), 4.24 (brd, J = 8.3 Hz, 1 H, 3-H), 6.77 (d,

J = 8.7 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.83 (d, J = 8.9 Hz, 2 H, 3Ј,5Ј-H), 7.21

(d, J = 8.7 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.36 (d, J = 8.1 Hz, 1 H, 5-H), 7.39

(ddd, J = 7.8, 7.7, 1.1 Hz, 1 H, 7-H), 7.44 (s, 1 H, 1-H), 7.44 (d, J

= 8.9 Hz, 2 H, 2Ј,6Ј-H), 7.60 (ddd, J = 8.1, 7.7, 1.7 Hz, 1 H, 6-H),

8.29 (dd, J = 7.8, 1.7 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 36.8 (C-

3-(3,4-Dimethoxyphenyl)-2-phenyl-3,4-dihydro-9H-xanthen-9-one

1

(6j): Yellowish oil. H NMR: δ = 2.99 (dd, J = 17.3, 1.5 Hz, 1 H,

2654

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

4_trans-H), 3.63 (dd, J = 17.3, 8.9 Hz, 1 H, 4_cis-H), 3.77 (s, 3 H, 3ЈЈ- (C-2ЈЈ,6ЈЈ), 129.9 (C-2Ј,6Ј), 137.0 (C-2), 139.88 and 139.94 (C-1Ј,

OCH₃), 3.79 (s, 3 H, 4ЈЈ-OCH₃), 4.25 (dd, J = 8.9, 1.5 Hz, 1 H, 3- C-1ЈЈ), 147.0 (C-3), 155.2 (C-4a), 158.2 (C-4b), 165.0 (C-6), 176.0

H), 6.71 (d, J = 8.2 Hz, 1 H, 5ЈЈ-H), 6.82 (d, J = 2.0 Hz, 1 H, 2ЈЈ-

H), 6.85 (dd, J = 8.2, 2.0 Hz, 1 H, 6ЈЈ-H), 7.22–7.32 (m, 3 H,

3Ј,4Ј,5Ј-H), 7.36 (d, J = 8.0 Hz, 1 H, 5-H), 7.38 (ddd, J = 7.8, 7.7,

1.3 Hz, 1 H, 7-H), 7.47–7.50 (m, 2 H, 2Ј,6Ј-H), 7.54 (s, 1 H, 1-H),

7.60 (ddd, J = 8.0, 7.7, 1.6 Hz, 1 H, 6-H), 8.28 (dd, J = 7.8, 1.6 Hz,

1 H, 8-H) ppm. ¹³C NMR: δ = 37.0 (C-4), 41.3 (C-3), 55.7 and

55.8 (3ЈЈ,4ЈЈ-OCH₃), 110.3 (C-2ЈЈ), 111.4 (C-5ЈЈ), 116.6 (C-1), 116.7

(C-9a), 118.0 (C-5), 119.2 (C-6ЈЈ), 123.8 (C-8a), 125.0 (C-7), 125.6

(C-2Ј,6Ј), 126.1 (C-8), 127.5 (C-4Ј), 128.4 (C-3Ј,5Ј), 132.99 and

133.01 (C-6, C-1ЈЈ), 135.6 (C-2), 139.1 (C-1Ј), 148.0 (C-4ЈЈ), 149.1

(C-3ЈЈ), 155.8 (C-4b), 162.6 (C-4a), 174.1 (C-9) ppm. EI-MS: m/z

(%) = 410 [M]^+·(100), 409 (53), 408 (73), 395 (18), 393 (19), 379

(10), 377 (12), 361 (18), 334 (16), 333 (46), 321 (11), 299 (31), 273

(27), 215 (10), 202 (8), 165 (12), 151 (11), 105 (14), 86 (17), 84 (26).

HRMS (EI): calcd. for C₂₇H₂₂O₄[M]^+·410.1518; found 410.1515.

(C-9) ppm. EI-MS: m/z (%) = 378 [M]^+·(100), 377 (63), 363 (13),

335 (7), 334 (16), 277 (5), 276 (7), 228 (5), 226 (5). C₂₆H₁₈O₃

(378.42): calcd. for C 82.52, H 4.79; found C 82.56, H 4.92.

6-Methoxy-2,3-diphenyl-3,4-dihydro-9H-xanthen-9-one (6m): Yel-

lowish oil. ¹H NMR: δ = 2.96 (dd, J = 17.3, 1.5 Hz, 1 H, 4_trans-H),

3.64 (dd, J = 17.3, 9.0 Hz, 1 H, 4_cis-H), 3.85 (s, 3 H, 6-OCH₃), 4.28

(dd, J = 9.0, 1.5 Hz, 1 H, 3-H), 6.74 (d, J = 2.4 Hz, 1 H, 5-H), 6.95

(dd, J = 8.9, 2.4 Hz, 1 H, 7-H), 7.18–7.32 (m, 8 H, 3Ј,4Ј,5Ј-H, 3-

C₆H₅), 7.45–7.48 (m, 2 H, 2Ј,6Ј-H), 7.54 (s, 1 H, 1-H), 8.18 (d, J =

8.9 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 36.6 (C-4), 41.7 (C-3), 55.7

(6-OCH₃), 100.4 (C-5), 114.2 (C-7), 116.6 (C-9a), 116.9 (C-1), 117.7

(C-8a), 125.6 (C-2Ј,6Ј), 127.1 (C-4Ј), 127.3 (C-2ЈЈ,6ЈЈ), 127.46 and

127.49 (C-8, C-4ЈЈ), 128.4 (C-3Ј,5Ј), 128.9 (C-3ЈЈ,5ЈЈ), 135.0 (C-2),

139.1 (C-1Ј), 140.8 (C-1ЈЈ), 157.5 (C-4b), 161.8 (C-4a), 163.5 (C-6),

173.8 (C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(8), 379 (20), 378

(100), 377 (51), 363 (11), 334 (11), 303 (8). HRMS (EI): calcd. for

C₂₆H₂₀O₃[M]^+·380.1412; found 380.1444.

3-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)-9H-xanthen-9-one

(5k) and 3-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)-3,4-dihydro-

9H-xanthen-9-one (6k): These compounds showed spectroscopic

and analytical data identical to those previously reported.^[27]

1-Methoxy-6,7-diphenyl-9H-xanthen-9-one (5n): M.p. 203–205 °C.

¹H NMR: δ = 4.04 (s, 3 H, 8-OCH₃), 6.82 (dd, J = 8.4, 0.7 Hz, 1

H, 7-H), 7.07 (dd, J = 8.4, 0.7 Hz, 1 H, 5-H), 7.14–7.27 (m, 10 H,

2,3-C₆H₅), 7.47 (s, 1 H, 4-H), 7.61 (t, J = 8.4 Hz, 1 H, 6-H), 8.33

(s, 1 H, 1-H) ppm. ¹³C NMR: δ = 56.4 (8-OCH₃), 105.4 (C-7),

110.0 (C-5), 112.6 (C-8a), 118.9 (C-4), 121.8 (C-9a), 126.7 (C-4Ј),

127.4 (C-4ЈЈ), 127.9 (C-3Ј,5Ј), 128.0 (C-3ЈЈ,5ЈЈ), 128.4 (C-1), 129.6

(C-2ЈЈ,6ЈЈ), 129.9 (C-2Ј,6Ј), 134.8 (C-6), 136.8 (C-2), 139.9 (C-1Ј, C-

1ЈЈ), 146.9 (C-3), 154.1 (C-4a), 158.2 (C-4b), 160.7 (C-8), 176.3 (C-

9) ppm. EI-MS: m/z (%) = 378 [M]^+·(100), 377 (23), 361 (10), 360

(8), 350 (9), 349 (60), 347 (10), 333 (13), 332 (42), 301 (6), 289 (8),

276 (6). C₂₆H₁₈O₃(378.42): calcd. for C 82.52, H 4.79; found C

82.27, H 4.73.

2,3-Bis(3,4-dimethoxyphenyl)-9H-xanthen-9-one (5l): M.p. 171–

173 °C. ¹H NMR: δ = 3.63 and 3.66 (2ϫs, 6 H, 4Ј,4ЈЈ-OCH₃), 3.88

and 3.89 (2ϫs, 6 H, 3Ј,3ЈЈ-OCH₃), 6.63 (brs, 2 H, 2Ј-H, 2ЈЈ-H),

6.80–6.89 (m, 4 H, 5Ј-H, 6Ј-H, 5ЈЈ-H, 6ЈЈ-H), 7.41 (dd, J = 8.2,

7.7 Hz, 1 H, 7-H), 7.52 (d, J = 8.1 Hz, 1 H, 5-H), 7.56 (s, 1 H, 4-

H), 7.75 (ddd, J = 8.1, 7.7, 1.6 Hz, 1 H, 6-H), 8.36 (s, 1 H, 1-H),

8.38 (dd, J = 8.2, 1.6 Hz, 1 H, 8-H) ppm. ¹³C NMR: δ = 55.69 and

55.71 (4Ј,4ЈЈ-OCH₃), 55.8 (3Ј,3ЈЈ-OCH₃), 110.8 (C-5Ј, C-5ЈЈ), 113.0

(C-2ЈЈ), 113.2 (C-2Ј), 118.0 (C-5), 119.1 (C-4), 120.4 (C-9a), 121.9

(C-6Ј, C-6ЈЈ), 122.2 (C-8a), 123.9 (C-7), 126.7 (C-8), 128.0 (C-1),

132.5 and 132.7 (C-1Ј, C-1ЈЈ), 134.8 (C-6), 136.7 (C-2), 147.3 (C-

3), 148.0, 148.3 and 148.6 (C-3Ј, C-4Ј, C-3ЈЈand C-4ЈЈ), 155.1 (C-

4a), 156.3 (C-4b), 177.0 (C-9) ppm. EI-MS: m/z (%) = 468 [M]^+·

(100), 453 (10), 379 (5), 97 (6). C₂₉H₂₄O₆(468.50): calcd. for C

74.35, H 5.16; found C 74.25, H 5.22.

1-Methoxy-6,7-diphenyl-7,8-dihydro-9H-xanthen-9-one (6n): M.p.

1

169–172 °C. H NMR: δ = 2.91 (dd, J = 17.3, 1.5 Hz, 1 H, 4_trans

-

H), 3.59 (dd, J = 17.3, 9.1 Hz, 1 H, 4_cis-H), 3.98 (s, 3 H, 8-OCH₃),

4.27 (dd, J = 9.1, 1.5 Hz, 1 H, 3-H), 6.77 (d, J = 8.3 Hz, 1 H, 7-

H), 6.89 (d, J = 8.3 Hz, 1 H, 5-H), 7.17–7.31 (m, 8 H, 3Ј,4Ј,5Ј-H,

3-C₆H₅), 7.45 (t, J = 8.3 Hz, 1 H, 6-H), 7.44–7.47 (m, 2 H, 2Ј,6Ј-

H), 7.55 (s, 1 H, 1-H) ppm. ¹³C NMR: δ = 36.2 (C-4), 41.7 (C-3),

56.3 (8-OCH₃), 106.3 (C-7), 110.1 (C-5), 114.4 (C-8a), 117.0 (C-1),

117.8 (C-9a), 125.8 (C-2Ј,6Ј), 127.1 and 127.4 (C-4Ј, C-4ЈЈ), 1273.

(C-2ЈЈ,6ЈЈ), 128.4 (C-3Ј,5Ј), 128.9 (C-3ЈЈ,5ЈЈ), 133.0 (C-6), 134.8 (C-

2), 139.2 (C-1Ј), 140.8 (C-1ЈЈ), 157.8 (C-4b), 160.09 and 161.13 (C-

8, C-4a), 173.9 (C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(58), 379

(28), 378 (100), 377 (28), 363 (13), 362 (11), 361 (23), 360 (11), 350

(14), 349 (69), 347 (15), 333 (20), 332 (46), 303 (17), 301 (11), 289

(21), 288 (14), 285 (14), 266 (27), 261 (10), 226 (9), 215 (8). HRMS

(EI): calcd. for C₂₆H₂₀O₃[M]^+·380.1412; found 380.1418.

2,3-Bis(3,4-dimethoxyphenyl)-3,4-dihydro-9H-xanthen-9-one (6l):

1

Yellowish oil. H NMR: δ = 2.98 (dd, J = 17.3, 1.5 Hz, 1 H, 4_trans

-

H), 3.63 (dd, J = 17.3, 8.3 Hz, 1 H, 4_cis-H), 3.77 and 3.79 (2ϫs, 6

H, 4Ј,4ЈЈ-OCH₃), 3.85 and 3.86 (2ϫs, 6 H, 3Ј,3ЈЈ-OCH₃), 4.23 (brd,

J = 8.3 Hz, 1 H, 3-H), 6.72 (d, J = 8.0 Hz, 1 H, 5ЈЈ-H), 6.76 (d, J

= 8.4 Hz, 1 H, 5Ј-H), 6.83 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 6.85 (dd, J

= 8.0, 2.0 Hz, 1 H, 6ЈЈ-H), 6.98 (dd, J = 8.4, 2.1 Hz, 1 H, 6Ј-H),

7.11 (d, J = 2.1 Hz, 1 H, 2Ј-H), 7.36 (dd, J = 8.5, 1.0 Hz, 1 H, 5-

H), 7.38 (dt, J = 7.7, 1.0 Hz, 1 H, 7-H), 7.45 (s, 1 H, 1-H), 7.60

(ddd, J = 8.5, 7.7, 1.7 Hz, 1 H, 6-H), 8.28 (dd, J = 7.7, 1.7 Hz, 1

H, 8-H) ppm. ¹³C NMR: δ = 36.7 (C-4), 41.5 (C-3), 55.7, 55.77

and 55.80 (3Ј,4Ј,3ЈЈ,4ЈЈ-OCH₃), 108.7 (C-2Ј), 110.2 (C-2ЈЈ), 110.8

(C-5Ј), 111.4 (C-5ЈЈ), 114.9 (C-1), 116.8 (C-9a), 117.9 (C-5), 118.2

(C-6Ј), 119.1 (C-6ЈЈ), 123.7 (C-8a), 125.0 (C-7), 126.1 (C-8), 132.0

(C-1Ј), 133.0 (C-6), 133.2 (C-1ЈЈ), 135.4 (C-2), 148.0, 148.7 and

149.1 (C-3Ј, C-4Ј, C-3ЈЈand C-4ЈЈ), 155.8 (C-4b), 162.3 (C-4a),

174.1 (C-9) ppm. EI-MS: m/z (%) = 470 [M]^+·(78), 469 (28), 468

(100), 455 (7), 453 (10), 421 (7), 333 (16), 332 (7), 84 (7). HRMS

(EI): calcd. for C₂₉H₂₆O₆[M]^+·470.1729; found 470.1739.

1-Hydroxy-6,7-diphenyl-9H-xanthen-9-one (12n): M.p. 160–162 °C.

¹H NMR: δ = 6.79 (dd, J = 8.4, 0.6 Hz, 1 H, 7-H), 6.91 (dd, J =

8.4, 0.6 Hz, 1 H, 5-H), 7.12–7.16 (m, 2 H, 2Ј,6Ј-H), 7.17–7.20 (m,

2 H, 2ЈЈ,6ЈЈ-H), 7.22–7.28 (m, 6 H, 3Ј,4Ј,5Ј-H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.49

(s, 1 H, 4-H), 7.57 (t, J = 8.4 Hz, 1 H, 6-H), 8.26 (s, 1 H, 1-H),

12.67 (s, 1 H, 8-OH) ppm. ¹³C NMR: δ = 107.0 (C-5), 109.0 (C-

8a), 110.5 (C-7), 119.3 (C-4, C-9a), 127.0 and 127.5 (C-4Ј, C-4ЈЈ),

127.7 (C-1), 128.0 and 128.1 (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 129.5 (C-2ЈЈ,6ЈЈ),

129.8 (C-2Ј,6Ј), 136.7 (C-6), 137.2 (C-2), 139.5 and 139.6 (C-1Ј, C-

1ЈЈ), 148.4 (C-3), 155.1 (C-4a), 156.3 (C-4b), 161.9 (C-8), 182.0 (C-

9) ppm. EI-MS: m/z (%) = 378 [M]^+·(100), 365 (16), 363 (40), 349

6-Methoxy-2,3-diphenyl-9H-xanthen-9-one (5m): M.p. 151–153 °C.

¹H NMR: δ = 3.95 (s, 3 H, 6-OCH₃), 6.91 (d, J = 2.4 Hz, 1 H, 5-

H), 6.96 (dd, J = 8.9, 2.4 Hz, 1 H, 7-H), 7.15–7.28 (m, 10 H, 2,3-

C₆H₅), 7.52 (s, 1 H, 4-H), 8.28 (d, J = 8.9 Hz, 1 H, 8-H), 8.36 (s,

1 H, 1-H) ppm. ¹³C NMR: δ = 55.8 (6-OCH₃), 100.2 (C-5), 113.3

(C-7), 115.9 (C-8a), 119.3 (C-4), 120.8 (C-9a), 126.8 (C-4Ј), 127.5 (12), 289 (6), 228 (6). HRMS (EI): calcd. for C₂₅H₁₆O₃[M]^+·

(C-4ЈЈ), 128.0 (C-3Ј,5Ј), 128.1 (C-3ЈЈ,5ЈЈ), 128.3 (C-1, C-8), 129.6 364.1099; found 364.1102.

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2655

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

1-Methoxy-7-(4-methoxyphenyl)-6-phenyl-9H-xanthen-9-one (5o): 408 (6), 395 (13), 391 (12), 380 (6), 363 (6), 351 (8). C₂₈H₂₂O₅

FULL PAPER

1

M.p. 192–194 °C. H NMR: δ = 3.79 (s, 3 H, 4Ј-OCH₃), 4.04 (s, 3

H, 8-OCH₃), 6.78 (d, J = 8.8 Hz, 2 H, 3Ј,5Ј-H), 6.82 (d, J = 8.3 Hz,

1 H, 7-H), 7.08 (d, J = 8.8 Hz, 2 H, 2Ј,6Ј-H), 7.08 (dd, J = 8.3,

0.8 Hz, 1 H, 5-H), 7.18–7.21 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.27–7.29 (m, 3

H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.46 (s, 1 H, 4-H), 7.62 (t, J = 8.3 Hz, 1 H, 6-H),

8.30 (s, 1 H, 1-H) ppm. ¹³C NMR: δ = 55.2 (4Ј-OCH₃), 56.5 (8-

OCH₃), 105.4 (C-7), 110.1 (C-5), 112.6 (C-8a), 113.4 (C-3Ј,5Ј),

118.9 (C-4), 121.9 (C-9a), 127.4 (C-4ЈЈ), 128.1 (C-3ЈЈ,5ЈЈ), 128.2 (C-

1), 129.6 (C-2ЈЈ,6ЈЈ), 131.0 (C-2Ј,6Ј), 132.4 (C-1Ј), 134.8 (C-6), 136.5

(C-2), 140.2 (C-1ЈЈ), 146.9 (C-3), 153.9 (C-4a), 158.2 (C-4b), 158.5

(C-4Ј), 160.8 (C-8), 176.4 (C-9) ppm. EI-MS: m/z (%) = 408 [M]^+·

(100), 407 (23), 391 (14), 390 (9), 380 (10), 379 (41), 363 (14), 362

(32), 347 (10), 346 (6), 305 (5). C₂₇H₂₀O₄(408.45): calcd. for C

79.40, H 4.94; found C 79.42, H 4.91.

(438.47): calcd. for C 76.70, H 5.06; found C 76.73, H 5.27.

7-(3,4-Dimethoxyphenyl)-1-methoxy-6-phenyl-3,4-dihydro-9H-

xanthen-9-one (6p): Yellowish oil. ¹H NMR: δ = 2.91 (dd, J = 17.3,

1.4 Hz, 1 H, 4_trans-H), 3.60 (dd, J = 17.3, 9.1 Hz, 1 H, 4_cis-H), 3.82

and 3.84 (2ϫs, 6 H, 3Ј,4Ј-OCH₃), 3.99 (s, 3 H, 8-OCH₃), 4.25 (dd,

J = 9.1, 1.4 Hz, 1 H, 3-H), 6.75 (d, J = 8.4 Hz, 1 H, 5Ј-H), 6.78

(dd, J = 8.4, 0.7 Hz, 1 H, 7-H), 6.90 (dd, J = 8.4, 0.7 Hz, 1 H, 5-

H), 6.95 (dd, J = 8.4, 2.1 Hz, 1 H, 6Ј-H), 7.07 (d, J = 2.1 Hz, 1 H,

2Ј-H), 7.18–7.31 (m, 5 H, 3-C₆H₅), 7.46 (s, 1 H, 1-H), 7.46 (t, J =

8.4 Hz, 1 H, 6-H) ppm. ¹³C NMR: δ = 36.1 (C-4), 41.9 (C-3), 55.74

and 55.84 (3Ј,4Ј-OCH₃), 56.4 (8-OCH₃), 106.3 (C-7), 108.7 (C-2Ј),

110.1 (C-5), 110.8 (C-5Ј), 114.5 (C-8a), 115.4 (C-1), 117.9 (C-9a),

118.2 (C-6Ј), 127.1 (C-4ЈЈ), 127.3 (C-2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ), 133.2

(C-1Ј), 133.0 (C-6), 135.6 (C-2), 141.1 (C-1ЈЈ), 148.7 and 148.8 (C-

3Ј, C-4Ј), 157.9 (C-4b), 159.7 (C-4a), 160.2 (C-8), 174.0 (C-9) ppm.

EI-MS: m/z (%) = 440 [M]^+·(22), 439 (24), 408 (100), 423 (20),

395 (10), 391 (9), 363 (8). HRMS (EI): calcd. for C₂₈H₂₄O₅[M]^+·

440.1624; found 440.1615.

1-Methoxy-7-(4-methoxyphenyl)-6-phenyl-7,8-dihydro-9H-xanthen-

9-one (6o): M.p. 168–170 °C. ¹H NMR: δ = 2.89 (dd, J = 17.3,

1.5 Hz, 1 H, 4_trans-H), 3.58 (dd, J = 17.3. 8.5 Hz, 1 H, 4_cis-H), 3.76

(s, 3 H, 4Ј-OCH₃), 3.98 (s, 3 H, 8-OCH₃), 4.24 (brd, J = 8.5 Hz, 1

H, 3-H), 6.76 (d, J = 8.4 Hz, 1 H, 7-H), 6.80 (d, J = 8.9 Hz, 2 H,

3Ј,5Ј-H), 6.89 (dd, J = 8.4, 0.7 Hz, 1 H, 5-H), 7.17–7.30 (m, 5 H,

3-C₆H₅), 7.40 (d, J = 8.9 Hz, 2 H, 2Ј,6Ј-H), 7.44 (t, J = 8.4 Hz, 1

H, 6-H), 7.45 (s, 1 H, 1-H) ppm. ¹³C NMR: δ = 36.1 (C-4), 41.7

(C-3), 55.2 (8-OCH₃), 56.3 (8-OCH₃), 106.2 (C-7), 110.1 (C-5),

113.8 (C-3Ј,5Ј), 114.4 (C-8a), 115.1 (C-1), 117.9 (C-9a), 126.8 (C-

2Ј,6Ј), 127.0 (C-4ЈЈ), 127.3 (C-2ЈЈ,6ЈЈ), 128.9 (C-3ЈЈ,5ЈЈ), 131.7 (C-

1Ј), 132.9 (C-6), 134.4 (C-2), 140.9 (C-1ЈЈ), 157.8 (C-4b), 159.0 (C-

4Ј), 159.6 (C-4a), 160.1 (C-8), 173.9 (C-9) ppm. EI-MS: m/z (%) =

410 [M]^+·(10), 409 (28), 408 (100), 407 (34), 391 (21), 390 (15), 380

(18), 379 (62), 363 (26), 362 (43), 347 (16), 305 (9), 153 (10), 152

(13), 137 (14), 121 (21), 99 (16), 78 (9). HRMS (EI): calcd. for

C₂₇H₂₂O₄[M]^+·410.1518; found 410.1505.

7-(3,4-Dimethoxyphenyl)-1-hydroxy-6-phenyl-9H-xanthen-9-one

(12p): M.p. 186–188 °C. ¹H NMR: δ = 3.56 (s, 3 H, 4Ј-OCH₃), 3.88

(s, 3 H, 3Ј-OCH₃), 6.52 (d, J = 1.9 Hz, 1 H, 2Ј-H), 6.80 (d, J =

8.2 Hz, 1 H, 5Ј-H), 6.82 (d, J = 8.3 Hz, 1 H, 7-H), 6.84 (dd, J =

8.2, 1.9 Hz, 1 H, 6Ј-H), 6.95 (dd, J = 8.3, 0.7 Hz, 1 H, 5-H), 7.20–

7.24 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.28–7.32 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.52 (s,

1 H, 4-H), 7.61 (t, J = 8.3 Hz, 1 H, 6-H), 8.30 (s, 1 H, 1-H), 12.69

(s, 1 H, 8-OH) ppm. ¹³C NMR: δ = 55.5 (4Ј-OCH₃), 55.7 (3Ј-

OCH₃), 107.0 (C-5), 109.0 (C-8a), 110.5 (C-7), 110.7 (C-5Ј), 113.3

(C-2Ј), 119.3 (C-4), 119.4 (C-9a), 122.1 (C-6Ј), 127.0 (C-1), 127.7

(C-4ЈЈ), 128.2 (C-3ЈЈ,5ЈЈ), 129.4 (C-2ЈЈ,6ЈЈ), 132.0 (C-1Ј), 136.7 (C-

6), 136.9 (C-2), 139.9 (C-1ЈЈ), 148.09 and 148.12 (C-3Ј,4Ј), 148.4

(C-3), 155.0 (C-4a), 156.4 (C-4b), 161.9 (C-8) 182.1 (C-9) ppm. EI-

MS: m/z (%) = 424 [M]^+·(100), 409 (20), 381 (10), 377 (14), 363

(10), 349 (13), 337 (10), 139 (10), 137 (14), 125 (12), 111 (16), 110

(13), 97 (19), 96 (13), 86 (13), 84 (19), 83 (15), 81 (16), 73 (12), 69

(17). C₂₇H₂₀O₅(424.45): calcd. for C 76.40, H 4.75; found C 76.11,

H 4.75.

1-Hydroxy-7-(4-methoxyphenyl)-6-phenyl-9H-xanthen-9-one (12o):

1

M.p. 126–128 °C. H NMR: δ = 3.79 (s, 3 H, 4Ј-OCH₃), 6.77 (d, J

= 8.8 Hz, 2 H, 3Ј,5Ј-H), 6.81 (dd, J = 8.4, 0.7 Hz, 1 H, 7-H), 6.93

(dd, J = 8.4, 0.7 Hz, 1 H, 5-H), 7.07 (d, J = 8.8 Hz, 2 H, 2Ј,6Ј-H),

7.18–7.21 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.26–7.30 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.49

(s, 1 H, 4-H), 7.59 (t, J = 8.4 Hz, 1 H, 6-H), 8.25 (s, 1 H, 1-H),

12.70 (s, 1 H, 8-OH) ppm. ¹³C NMR: δ = 55.2 (4Ј-OCH₃), 107.0

(C-5), 109.0 (C-8a), 110.5 (C-7), 113.5 (C-3Ј,5Ј), 119.35 (C-4),

119.38 (C-9a), 127.3 (C-4ЈЈ), 127.7 (C-1), 128.2 (C-3ЈЈ,5ЈЈ), 129.5

(C-2ЈЈ,6ЈЈ), 131.0 (C-2Ј,6Ј), 131.9 (C-1Ј), 136.7 (C-6), 136.9 (C-2),

139.8 (C-1ЈЈ), 148.4 (C-3), 155.0 (C-4a), 156.4 (C-4b), 158.7 (C-4Ј),

161.9 (C-8) 182.1 (C-9) ppm. EI-MS: m/z (%) = 394 [M]^+·(100),

393 (15), 395 (25), 379 (15), 363 (15), 351 (10), 129 (17), 125 (11),

123 (10), 111 (17), 97 (22), 96 (13), 86 (14), 84 (16), 83 (21), 73 (12),

69 (12). HRMS (EI): calcd. for C₂₇H₂₂O₄[M]^+·394.1205; found

394.1204.

6-(3,4-Dimethoxyphenyl)-1-methoxy-7-phenyl-9H-xanthen-9-one

(5q): M.p. 188–190 °C. ¹H NMR: δ = 3.52 (s, 3 H, 3ЈЈ-OCH₃), 3.88

(s, 3 H, 4ЈЈ-OCH₃), 4.04 (s, 3 H, 8-OCH₃), 6.54 (d, J = 2.0 Hz, 1

H, 2ЈЈ-H), 6.82 (d, J = 8.4 Hz, 2 H, 5ЈЈ-H, 7-H), 6.90 (dd, J = 8.4,

2.0 Hz, 1 H, 6ЈЈ-H), 7.09 (dd, J = 8.4, 0.8 Hz, 1 H, 5-H), 7.17–7.20

(m, 2 H, 2Ј,6Ј-H), 7.23–7.27 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.50 (s, 1 H, 4-

H), 7.62 (t, J = 8.4 Hz, 1 H, 6-H), 8.31 (s, 1 H, 1-H) ppm. ¹³C

NMR: δ = 55.5 (3ЈЈ-OCH₃), 55.8 (4ЈЈ-OCH₃), 56.5 (8-OCH₃), 105.5

(C-7), 110.0 (C-5), 110.7 (C-5ЈЈ), 112.6 (C-8a), 113.3 (C-2ЈЈ), 118.3

(C-4), 121.6 (C-9a), 121.8 (C-6ЈЈ), 126.7 (C-4Ј), 128.1 (C-3Ј,5Ј),

128.4 (C-1), 129.9 (C-2Ј,6Ј), 132.3 (C-1ЈЈ), 134.6 (C-6), 136.8 (C-2),

140.4 (C-1Ј), 146.6 (C-3), 148.1 and 148.5 (C-3ЈЈ, C-4ЈЈ), 154.2 (C-

4a), 158.2 (C-4b), 160.8 (C-8), 176.3 (C-9) ppm. EI-MS: m/z (%) =

438 [M]^+·(100), 437 (19), 422 (5), 421 (18), 420 (8), 410 (8), 409

(35), 393 (13), 392 (20), 377 (6), 376 (5), 361 (6), 333 (5). C₂₈H₂₂O₅

(438.47): calcd. for C 76.70, H 506; found C 76.66, H 5.11.

7-(3,4-Dimethoxyphenyl)-1-methoxy-6-phenyl-9H-xanthen-9-one

1

(5p): M.p. 189–190 °C. H NMR: δ = 3.55 (s, 3 H, 3Ј-OCH₃), 3.87

(s, 3 H, 4Ј-OCH₃), 4.04 (s, 3 H, 8-OCH₃), 6.53 (d, J = 1.9 Hz, 1 H,

2Ј-H), 6.80 (d, J = 8.3 Hz, 1 H, 5Ј-H), 6.83 (dd, J = 8.6, 0.9 Hz, 1

H, 7-H), 6.85 (dd, J = 8.3, 1.9 Hz, 1 H, 6Ј-H), 7.09 (dd, J = 8.6,

0.9 Hz, 1 H, 5-H), 7.19–7.22 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.27–7.31 (m, 3

6-(3,4-Dimethoxyphenyl)-1-methoxy-7-phenyl-7,8-dihydro-9H-

H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.47 (s, 1 H, 4-H), 7.62 (t, J = 8.6 Hz, 1 H, 6-H), xanthen-9-one (6q): Yellowish oil. ¹H NMR: δ = 2.91 (dd, J = 17.3,

8.35 (s, 1 H, 1-H) ppm. ¹³C NMR: δ = 55.5 (3Ј-OCH₃), 55.8 (4Ј- 1.4 Hz, 1 H, 4_trans-H), 3.58 (dd, J = 17.3, 8.6 Hz, 1 H, 4_cis-H), 3.76

OCH₃), 56.5 (8-OCH₃), 105.4 (C-7), 110.1 (C-5), 110.7 (C-5Ј), (s, 3 H, 3ЈЈ-OCH₃), 3.80 (s, 3 H, 4ЈЈ-OCH₃), 3.99 (s, 3 H, 8-OCH₃),

112.6 (C-8a), 113.5 (C-2Ј), 118.8 (C-4), 121.9 (C-9a), 122.1 (C-6Ј), 4.22 (dd, J = 8.6, 1.4 Hz, 1 H, 3-H), 6.72 (d, J = 8.2 Hz, 1 H, 5ЈЈ-

127.4 (C-4ЈЈ), 128.0 (C-1), 128.2 (C-3ЈЈ,5ЈЈ), 129.5 (C-2ЈЈ,6ЈЈ), 132.4 H), 6.79 (d, J = 8.4 Hz, 1 H, 7-H), 6.81 (d, J = 2.0 Hz, 1 H, 2ЈЈ-

(C-1Ј), 134.8 (C-6), 136.5 (C-2), 140.3 (C-1ЈЈ), 146.9 (C-3), 147.9

and 148.0 (C-3Ј, C-4Ј), 154.0 (C-4a), 158.2 (C-4b), 160.8 (C-8),

176.4 (C-9) ppm. EI-MS: m/z = 438 [M]^+·(100), 424 (7), 423 (25),

H), 6.84 (dd, J = 8.2, 2.0 Hz, 1 H, 6ЈЈ-H), 6.92 (dd, J = 8.4, 0.7 Hz,

1 H, 5-H), 7.19–7.31 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.46 (d, J = 8.4 Hz, 2 H,

2Ј,6Ј-H), 7.47 (t, J = 8.4 Hz, 1 H, 6-H), 7.53 (s, 1 H, 1-H) ppm.

2656

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

¹³C NMR: δ = 36.5 (C-4), 41.5 (C-3), 55.78 and 55.82 (3ЈЈ,4ЈЈ-

OCH₃), 3.88 and 3.89 (2ϫs, 6 H, 3Ј,3ЈЈ-OCH₃), 6.64–6.66 (m, 2

OCH₃), 56.4 (8-OCH₃), 106.3 (C-7), 110.2 (C-5), 110.3 (C-2ЈЈ), H, 2Ј-H, 2ЈЈ-H), 6.79–6.88 (m, 5 H, 7-H, 5Ј-H, 6Ј-H, 5ЈЈ-H, 6ЈЈ-H),

111.4 (C-5ЈЈ), 114.4 (C-8a), 116.9 (C-1), 117.7 (C-9a), 119.3 (C-6ЈЈ), 6.94 (dd, J = 8.4, 0.6 Hz, 1 H, 5Ј-H), 7.52 (s, 1 H, 4-H), 7.60 (t, J

125.6 (C-2Ј,6Ј), 127.4 (C-4Ј), 128.5 (C-3Ј,5Ј), 133.1 (C-6), 133.2 (C-

1ЈЈ), 135.2 (C-2), 139.4 (C-1Ј), 148.0 (C-4ЈЈ), 149.1 (C-3ЈЈ), 157.9 ¹³C NMR: δ = 55.68 and 55.71 (4Ј,4ЈЈ-OCH₃), 55.8 (3Ј,3ЈЈ-OCH₃),

(C-4b), 160.2 (C-8), 160.3 (C-4a), 174.0 (C-9) ppm. EI-MS: m/z (%) 107.0 (C-5), 109.0 (C-8a), 110.5 (C-7), 110.77 and 110.81 (C-5Ј, C-

= 440 [M]^+·(18), 439 (23), 438 (100), 437 (23), 421 (24) 420 (11), 5ЈЈ), 112.9 and 113.1 (C-2Ј, C-2ЈЈ), 118.4 (C-4), 119.1 (C-9a), 121.9

= 8.4 Hz, 1 H, 6-H), 8.26 (s, 1 H, 1-H), 12.70 (s, 1 H, 8-OH) ppm.

410 (10), 409 (42), 393 (18), 392 (25), 361 (8), 151 (8), 137 (9).

and 122.1 (C-6Ј, C-6ЈЈ), 127.1 (C-1), 132.2 and 132.4 (C-1Ј, C-1ЈЈ),

136.7 (C-6), 136.9 (C-2), 148.11, 148.13, 148.36, 148.38 and 148.7

(C-3, C-3Ј, C-4Ј, C-3ЈЈ, C-4ЈЈ), 155.1 (C-4a), 156.3 (C-4b), 161.9

(C-8), 182.0 (C-9) ppm. EI-MS: m/z (%) = 484 [M]^+·(100), 469 (9),

185 (12), 129 (19), 111 (10), 97 (16), 83 (13), 73 (20), 71 (10), 69

(13), 60 (12). HRMS (EI): calcd. for C₂₉H₂₄O₇[M]^+·484.1522;

found 484.1523.

HRMS (EI): calcd. for C₂₈H₂₄O₅[M]^+·440.1624; found 440.1627.

6-(3,4-Dimethoxyphenyl)-1-hydroxy-7-phenyl-9H-xanthen-9-one

(12q): M.p. 165–167 °C. ¹H NMR: δ = 3.53 (s, 3 H, 3ЈЈ-OCH₃),

3.89 (s, 3 H, 4ЈЈ-OCH₃), 6.55 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 6.83 (dd,

J = 8.4, 0.7 Hz, 1 H, 7-H), 6.84 (d, J = 8.3 Hz, 1 H, 5ЈЈ-H), 6.92

(dd, J = 8.3, 2.0 Hz, 1 H, 6ЈЈ-H), 6.97 (dd, J = 8.4, 0.7 Hz, 1 H, 5-

H), 7.17–7.20 (m, 2 H, 2Ј,6Ј-H), 7.25–7.30 (m, 3 H, 3Ј,4Ј,5Ј-H),

1,3-Dimethoxy-6,7-diphenyl-9H-xanthen-9-one (5s): M.p. 209–

7.56 (s, 1 H, 4-H), 7.61 (t, J = 8.4 Hz, 1 H, 6-H), 8.28 (s, 1 H, 1- 210 °C. ¹H NMR: δ = 3.93 (s, 3 H, 6-OCH₃), 4.00 (s, 3 H, 8-OCH₃),

H), 12.71 (s, 1 H, 8-OH) ppm. ¹³C NMR: δ = 55.6 (3ЈЈ-OCH₃), 6.37 (d, J = 2.3 Hz, 1 H, 7-H), 6.53 (d, J = 2.3 Hz, 1 H, 5-H), 7.14–

55.8 (4ЈЈ-OCH₃), 107.0 (C-5), 109.1 (C-8a), 110.6 (C-7), 110.8 (C-

7.27 (m, 10 H, 2,3-C₆H₅), 7.43 (s, 1 H, 4-H), 8.32 (s, 1 H, 1-H) ppm.

5ЈЈ), 113.3 (C-2ЈЈ), 118.8 (C-4), 119.2 (C-9a), 1220 (C-6ЈЈ), 127.0 ¹³C NMR: δ = 55.8 (6-OCH₃), 56.4 (8-OCH₃), 92.9 (C-5), 95.2 (C-

(C-4Ј), 127.6 (C-1), 128.2 (C-3Ј,5Ј), 129.8 (C-2Ј,6Ј), 132.0 (C-1ЈЈ),

136.7 (C-6), 137.2 (C-2), 140.0 (C-1Ј), 148.1 (C-3), 148.2 (C-3ЈЈ),

148.8 (C-4ЈЈ), 155.4 (C-4a), 156.4 (C-4b), 162.0 (C-8), 182.1 (C-

9) ppm. EI-MS: m/z (%) = 424 [M]^+·(100), 409 (12), 393 (12), 377

(11), 350 (8), 349 (13), 337 (8), 84 (10). HRMS (EI): calcd. for

C₂₇H₂₀O₅[M]^+·424.1311; found 424.1312.

7), 107.4 (C-8a), 118.4 (C-4), 122.0 (C-9a), 126.7 (C-4Ј), 127.4 (C-

4ЈЈ), 128.0 (C-3Ј,5Ј), 128.1 (C-3ЈЈ,5ЈЈ), 128.4 (C-1), 129.6 (C-2ЈЈ,6ЈЈ),

130.0 (C-2Ј,6Ј), 136.8 (C-2), 140.05 and 140.08 (C-1Ј, C-1ЈЈ), 146.4

(C-3), 154.1 (C-4a), 159.9 (C-4b), 162.0 (C-8), 164.9 (C-6), 175.2

(C-9) ppm. EI-MS: m/z (%) = 408 [M]^+·(100), 407 (40), 394 (5),

391 (13), 390 (8), 380 (14), 379 (66), 378 (15), 377 (39), 363 (13),

362 (27), 336 (7), 334 (14), 333 (13), 276 (6), 226 (5), 215 (8), 189

(5). C₂₇H₂₀O₄(408.45): calcd. for C 79.40, H 4.94; found C 79.22,

H 5.00.

6,7-Bis(3,4-dimethoxyphenyl)-1-methoxy-9H-xanthen-9-one (5r):

1

M.p. 187–188 °C. H NMR: δ = 3.62 and 3.65 (2ϫs, 6 H, 4Ј,4ЈЈ-

OCH₃), 3.88 and 3.89 (2ϫs, 6 H, 3Ј,3ЈЈ-OCH₃), 4.04 (s, 3 H, 8-

OCH₃), 6.65–6.66 (m, 2 H, 2Ј-H, 2ЈЈ-H), 6.79–6.84 (m, 5 H, 7-H,

5Ј-H, 6Ј-H, 5ЈЈ-H, 6ЈЈ-H), 7.09 (dd, J = 8.4, 0.7 Hz, 1 H, 5-H), 7.48 M.p. 189–191 °C. H NMR: δ = 2.90 (dd, J = 17.2, 1.4 Hz, 1 H,

1,3-Dimethoxy-6,7-diphenyl-7,8-dihydro-9H-xanthen-9-one (6s):

1

(s, 1 H, 4-H), 7.62 (t, J = 8.4 Hz, 1 H, 6-H), 8.32 (s, 1 H, 1-H) ppm.

¹³C NMR: δ = 55.7 (4Ј,4ЈЈ-OCH₃), 55.8 (3Ј,3ЈЈ-OCH₃), 56.5 (8-

OCH₃), 105.5 (C-7), 110.0 (C-5), 110.76 and 110.80 (C-5Ј, C-5ЈЈ),

4_trans-H), 3.61 (dd, J = 17.2, 8.9 Hz, 1 H, 4_cis-H), 3.86 (s, 3 H, 6-

OCH₃), 3.98 (s, 3 H, 8-OCH₃), 4.28 (brd, J = 8.9 Hz, 1 H, 3-H),

6.36 and 6.37 (AB, J = 2.6 Hz, 2 H, 5-H, 7-H), 7.21–7.33 (m, 8 H,

112.6 (C-8a), 113.0 and 113.3 (C-2Ј, C-2ЈЈ), 118.4 (C-4), 121.7 (C- 3Ј,4Ј,5Ј-H, 3-C₆H₅), 7.46–7.49 (m, 2 H, 2Ј,6Ј-H), 7.56 (s, 1 H, 1-

9a), 121.9 and 122.2 (C-6Ј, C-6ЈЈ), 128.1 (C-1), 132.7 and 132.9 (C-

1Ј, C-1ЈЈ), 134.8 (C-6), 136.5 (C-2), 146.7 (C-3), 147.9, 148.3 and

H) ppm. ¹³C NMR: δ = 36.2 (C-4), 41.8 (C-3), 55.6 (6-OCH₃), 56.3

(8-OCH₃), 92.8 (C-5), 96.0 (C-7), 109.1 (C-8a), 117.2 (C-1), 117.6

148.5 (C-3Ј, C-4Ј, C-3ЈЈ, C-4ЈЈ), 154.0 (C-4a), 158.2 (C-4b), 160.8 (C-9a), 125.6 (C-2Ј,6Ј), 127.1 and 127.3 (C-4Ј, C-4ЈЈ), 127.4 (C-

(C-8), 176.3 (C-9) ppm. EI-MS: m/z (%) = 498 [M]^+·(100), 497 2ЈЈ,6ЈЈ), 128.4 (C-3Ј,5Ј), 128.9 (C-3ЈЈ,5ЈЈ), 134.6 (C-2), 139.3 (C-1Ј),

(16), 481 (15), 480 (7), 470 (9), 469 (26), 453 (9), 452 (15), 409 (5), 140.9 (C-1ЈЈ), 159.39 and 159.43 (C-4a, C-4b), 161.3 (C-8), 163.4

406 (5), 361 (6), 141 (9), 99 (7), 86 (9), 84 (14), 78 (8). C₃₀H₂₆O₇(C-6), 173.3 (C-9) ppm. EI-MS: m/z (%) = 410 [M]^+·(17), 409 (29),

(498.52): calcd. for C 72.28, H 5.26; found C 72.33, H 5.24.

408 (100), 407 (45), 395 (15), 394 (45), 393 (23), 391 (20), 390 (10),

380 (23), 379 (82), 378 (24), 377 (49), 365 (13), 364 (12), 363 (21),

362 (32), 334 (19), 333 (20), 289 (11), 228 (11), 215 (12), 105 (11).

HRMS (EI): calcd. for C₂₇H₂₂O₄[M]^+·410.1518; found 410.1510.

6,7-Bis(3,4-dimethoxyphenyl)-1-methoxy-7,8-dihydro-9H-xanthen-9-

1

one (6r): Yellowish oil. H NMR: δ = 2.90 (dd, J = 17.3, 1.3 Hz, 1

H, 4_trans-H), 3.57 (dd, J = 17.3, 8.3 Hz, 1 H, 4_cis-H), 3.76, 3.80,

3.85 and 3.85 (4ϫs, 12 H, 3Ј,4Ј,3ЈЈ,4ЈЈ-OCH₃), 3.99 (s, 3 H, 8- 1-Hydroxy-3-methoxy-6,7-diphenyl-9H-xanthen-9-one (12s): M.p.

OCH₃), 4.20 (brd, J = 8.3 Hz, 1 H, 3-H), 6.72 (d, J = 8.2 Hz, 1 H,

5ЈЈ-H), 6.76 (d, J = 8.5 Hz, 1 H, 5Ј-H), 6.79 (d, J = 8.5 Hz, 1 H,

197–200 °C. ¹H NMR: δ = 3.91 (s, 3 H, 6-OCH₃), 6.38 (d, J =

2.2 Hz, 1 H, 7-H), 6.46 (d, J = 2.2 Hz, 1 H, 5-H), 7.14–7.20 (m, 4

7-H), 6.82 (d, J = 2.0 Hz, 1 H, 2ЈЈ-H), 6.84 (dd, J = 8.2, 2.0 Hz, 1 H, 2Ј,6Ј-H, 2ЈЈ,6ЈЈ-H), 7.22–7.29 (m, 6 H, 3Ј,4Ј,5Ј-H, 3ЈЈ,4ЈЈ,5ЈЈ-H),

H, 6ЈЈ-H), 6.92 (dd, J = 8.7, 0.7 Hz, 1 H, 5-H), 6.96 (dd, J = 8.5, 7.49 (s, 1 H, 4-H), 8.27 (s, 1 H, 1-H), 12.91 (s, 1 H, 8-OH) ppm.

2.1 Hz, 1 H, 6Ј-H), 7.08 (d, J = 2.1 Hz, 1 H, 2Ј-H), 7.44 (s, 1 H, 1-

¹³C NMR: δ = 55.8 (6-OCH₃), 93.0 (C-5), 97.1 (C-7), 104.0 (C-8a),

119.1 (C-4), 119.5 (C-9a), 127.0 and 127.7 (C-4Ј, C-4ЈЈ), 127.5 (C-

H), 7.47 (dd, J = 8.7, 8.5 Hz, 1 H, 6-H) ppm. ¹³C NMR: δ = 36.4

(C-4), 41.6 (C-3), 55.78, 55.82 and 55.85 (3Ј,4Ј,3ЈЈ,4ЈЈ-OCH₃), 56.4 1), 128.0 and 128.2 (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 129.6 and 129.9 (C-2Ј,6Ј,

(8-OCH₃), 106.3 (C-7), 108.8 (C-2Ј), 110.16 (C-5), 110.24 (C-2ЈЈ), C-2ЈЈ,6ЈЈ), 137.2 (C-2), 139.67 and 139.74 (C-1Ј, C-1ЈЈ), 147.8 (C-

110.9 (C-5Ј), 111.4 (C-5ЈЈ), 114.4 (C-8a), 115.3 (C-1), 117.8 (C-9a),

3), 155.1 (C-4a), 157.8 (C-4b), 163.6 (C-8), 166.7 (C-6), 180.6 (C-

118.2 (C-6Ј), 119.2 (C-6ЈЈ), 132.3 (C-1Ј), 133.0 (C-6), 133.5 (C-1ЈЈ), 9) ppm. EI-MS: m/z (%) = 394 [M]^+·(100), 393 (31), 365 (16), 350

135.0 (C-2), 148.0, 148.7, 148.8 and 149.1 (C-3Ј, C-4Ј, C-3ЈЈ, C-

4ЈЈ), 157.9 (C-4b), 159.9 (C-4a), 160.2 (C-8), 174.0 (C-9) ppm. EI-

MS: m/z (%) = 500 [M]^+·(21), 499 (24), 498 (100), 497 (12), 481

(13), 469 (21), 452 (12), 363 (7). HRMS (EI): calcd. for C₃₀H₂₈O₇

[M]^+·500.1835; found 500.1837.

(6). HRMS (EI): calcd. for C₂₆H₁₈O₄[M]^+·394.1205; found

394.1209.

Synthesis of the Hydroxylated 2,3-Diaryl-9H-xanthen-9-ones 13b–s:

A solution of the appropriate 2,3-diaryl-9H-xanthen-9-one (5b–s)

in recently distilled dichloromethane (3 mL) was cooled to –78 °C

and placed under nitrogen. A solution of boron tribromide in

dichloromethane (0.1 , 2.5 equiv. for each methyl group to be

6,7-Bis(3,4-dimethoxyphenyl)-1-hydroxy-9H-xanthen-9-one (12r):

1

M.p. 164–166 °C. H NMR: δ = 3.63 and 3.66 (2ϫs, 6 H, 4Ј,4ЈЈ-

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2657

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

cleaved) was gradually added. The reaction mixture was stirred and

left at room temperature for a period of time according to the sub-

stitution of the compounds (one hour for each group to be cleaved).

After that period, the solution was poured into water (20 mL) and

vigorously stirred until the formation of a yellow precipitate. The

solid was washed abundantly with water (4ϫ50 mL) and then with

light petroleum (4ϫ20 mL) to afford the hydroxylated 2,3-diaryl-

9H-xanthen-9-one (13b–s) in good yields.

(d, J = 8.6 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 6.94 (d, J = 8.7 Hz, 2 H, 2Ј,6Ј-H),

7.02 (d, J = 8.6 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.47 (t, J = 7.8 Hz, 1 H, 7-H),

7.51 (s, 1 H, 4-H), 7.63 (d, J = 8.0 Hz, 1 H, 5-H), 7.87 (ddd, J =

8.0, 7.8, 1.6 Hz, 1 H, 6-H), 7.98 (s, 1 H, 1-H), 8.19 (dd, J = 7.8,

1.6 Hz, 1 H, 8-H), 9.51 and 9.64 (2ϫs, 2 H, 4Ј,4ЈЈ-OH) ppm. ¹³C

NMR (500 MHz, [D₆]DMSO): δ = 115.1 (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 118.2

(C-5), 118.9 (C-4), 119.5 (C-9a), 121.2 (C-8a), 124.4 (C-7), 126.0

(C-8), 127.0 (C-1), 130.0 (C-1ЈЈ), 130.4 (C-1Ј), 130.6 (C-2Ј,6Ј), 130.7

(C-2ЈЈ,6ЈЈ), 135.6 (C-6), 136.6 (C-2), 147.3 (C-3), 154.4 (C-4a),

155.7 (C-4b), 156.4 (C-4Ј), 157.1 (C-4ЈЈ), 175.7 (C-9) ppm. EI-MS:

m/z (%) = 380 [M]^+·(43), 363 (2), 321 (1), 305 (1), 264 (2), 236 (3),

174 (100), 158 (70), 144 (28), 131 (48), 121 (30), 115 (26), 105 (54),

91 (27), 77 (64), 65 (20), 53 (22), 51 (24). C₂₅H₁₆O₄(380.39): calcd.

for C 78.94, H 4.24; found C 78.95, H 4.23.

2-(4-Hydroxyphenyl)-3-phenyl-9H-xanthen-9-one (13b): Reaction

1

time 1 h, 72% yield; m.p. 241–242 °C. H NMR ([D₆]DMSO): δ =

6.66 (d, J = 8.5 Hz, 2 H, 3Ј,5Ј-H), 6.95 (d, J = 8.5 Hz, 2 H, 2Ј,6Ј-

H), 7.22–7.25 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.32–7.34 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H),

7.52 (t, J = 7.7 Hz, 1 H, 7-H), 7.64 (s, 1 H, 4-H), 7.69 (d, J =

8.1 Hz, 1 H, 5-H), 7.91 (ddd, J = 8.1, 7.7, 1.6 Hz, 1 H, 6-H), 8.06

(s, 1 H, 1-H), 8.23 (dd, J = 7.7, 1.6 Hz, 1 H, 8-H), 9.53 (s, 1 H, 4Ј-

3-(4-Hydroxyphenyl)-2-(3,4-dihydroxyphenyl)-9H-xanthen-9-one

OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 115.1 (C-3Ј,5Ј), 118.3 (C- (13f, 13i): Reaction time 24 h, 92% yield when obtained from com-

5), 119.5 (C-4), 120.1 (C-9a), 121.2 (C-8a), 124.5 (C-7), 126.1 (C-

8), 127.0 (C-1), 127.7 (C-4ЈЈ), 128.3 (C-3ЈЈ,5ЈЈ), 129.4 (C-2ЈЈ,6ЈЈ), 261 °C. H NMR ([D₆]DMSO): δ = 6.41 (dd, J = 8.1, 2.1 Hz, 1 H,

130.0 (C-1Ј), 130.7 (C-2Ј,6Ј), 135.6 (C-6), 136.7 (C-2), 139.5 (C- 6Ј-H), 6.58 (d, J = 2.1 Hz, 1 H, 2Ј-H), 6.65 (d, J = 8.1 Hz, 1 H, 5Ј-

pound 5f, 3 h, 80% when obtained from compound 5i; m.p. 260–

1

1ЈЈ), 147.2 (C-3), 154.4 (C-4a), 155.8 (C-4b), 156.5 (C-4Ј), 175.8 (C-

9) ppm. EI-MS: m/z (%) = 364 [M]^+·(100), 349 (3), 335 (4), 305

(5), 276 (3), 244 (3), 213 (3), 173 (4), 138 (2), 77 (2). HRMS (EI):

calcd. for C₂₅H₁₆O₃[M]^+·364.1099; found 364.1100.

H), 6.71 (d, J = 8.6 Hz, 2 H, 3ЈЈ,5ЈЈ-H), 7.08 (d, J = 8.6 Hz, 2 H,

2ЈЈ,6ЈЈ-H), 7.51 (dd, J = 7.7, 7.4 Hz, 1 H, 7-H), 7.58 (s, 1 H, 4-H),

7.70 (d, J = 7.9 Hz, 1 H, 5-H), 7.90 (ddd, J = 7.9, 7.4, 1.6 Hz, 1

H, 6-H), 8.00 (s, 1 H, 1-H), 8.23 (dd, J = 7.7, 1.6 Hz, 1 H, 8-H),

8.95 (s, 1 H, 4Ј-OH), 9.01 (s, 1 H, 3Ј-OH), 9.65 (s, 1 H, 4ЈЈ-

OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 115.1 (C-3ЈЈ,5ЈЈ), 115.5 (C-

5Ј), 116.9 (C-2Ј), 118.3 (C-5), 118.9 (C-4), 119.5 (C-9a), 120.6 (C-

6Ј), 121.3 (C-8a), 124.4 (C-7), 126.1 (C-8), 127.0 (C-1), 130.0 (C-

1ЈЈ), 130.6 (C-2ЈЈ,6ЈЈ), 131.1 (C-1Ј), 135.6 (C-6), 136.8 (C-2), 144.5

(C-4Ј), 145.0 (C-3Ј), 147.3 (C-3), 154.4 (C-4a), 155.8 (C-4b), 157.2

(C-4ЈЈ), 175.8 (C-9) ppm. EI-MS: m/z (%) = 396 [M]^+·(100), 380

(7), 349 (7), 175 (5), 105 (1), 78 (15), 77 (5), 63 (21). C₂₅H₁₆O₅

(396.39): calcd. for C 75.75, H 4.07; found C 75.34, H 4.06.

2-(3,4-Dihydroxyphenyl)-3-phenyl-9H-xanthen-9-one (13c): Reac-

tion time 2 h, 80% yield; m.p. 171–173 °C. ¹H NMR ([D₆]DMSO):

δ = 6.37 (dd, J = 8.1, 2.0 Hz, 1 H, 6Ј-H), 6.58 (d, J = 2.0 Hz, 1 H,

2Ј-H), 6.63 (d, J = 8.1 Hz, 1 H, 5Ј-H), 7.24–7.30 (m, 2 H, 2ЈЈ,6ЈЈ-

H), 7.33–7.36 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.50 (dt, J = 7.7, 0.5 Hz, 1

H, 7-H), 7.60 (s, 1 H, 4-H), 7.67 (d, J = 8.2 Hz, 1 H, 5-H), 7.89

(ddd, J = 8.2, 7.7, 1.4 Hz, 1 H, 6-H), 8.03 (s, 1 H, 1-H), 8.22 (dd,

J = 7.7, 1.4 Hz, 1 H, 8-H), 8.94 and 8.99 (2 ϫ br s, 2 H, 3Ј,4Ј-

OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 115.5 (C-5Ј), 117.0 (C-2Ј),

118.3 (C-5), 119.4 (C-4), 120.0 (C-9a), 120.8 (C-6Ј), 121.2 (C-8a), 3-(3,4-Dihydroxyphenyl)-2-phenyl-9H-xanthen-9-one (13j): Reaction

1

124.5 (C-7), 126.1 (C-8), 127.0 (C-1), 127.7 (C-4ЈЈ), 128.2 (C-

time 2 h, 80% yield; m.p. 244–246 °C. H NMR ([D₆]DMSO): δ =

3ЈЈ,5ЈЈ), 129.3 (C-2ЈЈ,6ЈЈ), 130.7 (C-1Ј), 135.6 (C-6), 136.9 (C-2), 6.48 (dd, J = 8.1, 1.9 Hz, 1 H, 6ЈЈ-H), 6.62 (d, J = 1.9 Hz, 1 H, 2ЈЈ-

139.6 (C-1ЈЈ), 144.6 (C-3Ј), 145.0 (C-4Ј), 147.0 (C-3), 154.3 (C-4a), H), 6.65 (d, J = 8.1 Hz, 1 H, 5ЈЈ-H), 7.18–7.21 (m, 2 H, 2Ј,6Ј-H),

155.8 (C-4b), 175.8 (C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(100), 7.28–7.35 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.51 (dd, J = 7.9, 7.5 Hz, 1 H, 7-

363 (5), 333 (12), 321 (3), 305 (6), 292 (2), 276 (4), 263 (2), 239 (2), H), 7.55 (s, 1 H, 4-H), 7.68 (d, J = 8.1 Hz, 1 H, 5-H), 7.90 (ddd, J

213 (2), 181 (2), 167 (8), 152 (2), 138 (4), 121 (2), 77 (2). HRMS = 8.1, 7.5, 1.0 Hz, 1 H, 6-H), 8.05 (s, 1 H, 1-H), 8.22 (dd, J = 7.9,

(EI): calcd. for C₂₅H₁₆O₄[M]^+·380.1049; found 380.1035.

1.1 Hz, 1 H, 8-H), 8.97 (s, 1 H, 4ЈЈ-OH), 9.16 (s, 1 H, 3ЈЈ-OH) ppm.

¹³C NMR ([D₆]DMSO): δ = 115.4 (C-5ЈЈ), 116.9 (C-2ЈЈ), 118.3 (C-

5), 119.0 (C-4), 119.6 (C-9a), 120.9 (C-6ЈЈ), 121.3 (C-8a), 124.5 (C-

7), 126.1 (C-8), 127.0 (C-4Ј), 127.4 (C-1), 128.3 (C-3Ј,5Ј), 129.4 (C-

2Ј,6Ј), 130.3 (C-1ЈЈ), 135.6 (C-6), 136.5 (C-2), 140.0 (C-1Ј), 145.0

(C-3ЈЈ), 145.4 (C-4ЈЈ), 147.7 (C-3), 154.7 (C-4a), 155.8 (C-4b), 175.7

(C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(100), 379 (17), 363 (16),

334 (12), 333 (15), 167 (13), 129 (17), 115 (11), 111 (16), 105 (17),

97 (23), 96 (12), 95 (16), 85 (16), 84 (48), 83 (27), 77 (12), 73 (18),

71 (21), 69 (31), 66 (35), 60 (29). HRMS (EI): calcd. for C₂₅H₁₆O₄

[M]^+·380.1049; found 380.1048.

3-(4-Hydroxyphenyl)-2-phenyl-9H-xanthen-9-one (13d, 13g): Reac-

tion time 24 h, 69% yield when obtained from compound 5d; 1 h,

82 % when obtained from compound 5g; m.p. 244–245 °C. ¹H

NMR (500 MHz, [D₆]DMSO): δ = 6.69 (d, J = 8.6 Hz, 2 H, 3ЈЈ,5ЈЈ-

H), 7.05 (d, J = 8.6 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 7.19 (dd, J = 7.8, 1.5 Hz,

2 H, 2Ј,6Ј-H), 7.30–7.35 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.53 (ddd, J = 7.7,

7.6, 0.9 Hz, 1 H, 7-H), 7.65 (s, 1 H, 4-H), 7.71 (d, J = 8.1 Hz, 1 H,

5-H), 7.92 (ddd, J = 8.1, 7.6, 1.6 Hz, 1 H, 6-H), 8.08 (s, 1 H, 1-H),

8.24 (dd, J = 7.7, 1.6 Hz, 1 H, 8-H), 9.67 (s, 1 H, 4ЈЈ-OH) ppm.

¹³C NMR (500 MHz, [D₆]DMSO): δ = 115.1 (C-3ЈЈ,5ЈЈ), 118.3 (C-

5), 119.1 (C-4), 119.6 (C-9a), 121.3 (C-8a), 124.5 (C-7), 126.1 (C-

3-(3,4-Dihydroxyphenyl)-2-(4-hydroxyphenyl)-9H-xanthen-9-one

8), 127.0 (C-4Ј), 127.4 (C-1), 128.3 (C-3Ј,5Ј), 129.5 (C-2Ј,6Ј), 129.7 (13k): Reaction time 3 h, 94% yield. This compound showed spec-

(C-1ЈЈ), 130.8 (C-2ЈЈ,6ЈЈ), 135.6 (C-6), 136.5 (C-2), 139.9 (C-1Ј), troscopic and analytical data identical to those previously re-

147.4 (C-3), 154.8 (C-4a), 155.8 (C-4b), 157.2 (C-4ЈЈ), 175.7 (C-

9) ppm. EI-MS: m/z (%) = 364 [M]^+·(100), 347 (7), 335 (4), 305

(6), 289 (4), 276 (3), 244 (4), 213 (4), 173 (5), 138 (2), 84 (4), 66 (4).

C₂₅H₁₆O₃(364.39): calcd. for C 82.40, H 4.43; found C 82.50, H

4.43.

ported.^[27]

2,3-Bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (13l): Reaction

time 4 h, 70% yield; m.p. Ͼ 340 °C, dec. at 265 °C. ¹H NMR ([D₆]-

DMSO): δ = 6.42 (dd, J = 8.1, 2.1 Hz, 1 H, 6ЈЈ-H), 6.53 (dd, J =

8.0, 2.2 Hz, 1 H, 6Ј-H), 6.61 (d, J = 2.1 Hz, 1 H, 2ЈЈ-H), 6.65 (d, J

= 2.2 Hz, 1 H, 2Ј-H), 6.66 (d, J = 8.0 Hz, 1 H, 5Ј-H), 6.68 (d, J =

8.1 Hz, 1 H, 5ЈЈ-H), 7.50 (dt, J = 7.7, 0.8 Hz, 1 H, 7-H), 7.50 (s, 1

H, 4-H), 7.69 (d, J = 8.0 Hz, 1 H, 5-H), 7.89 (ddd, J = 8.0, 7.7,

2,3-Bis(4-hydroxyphenyl)-9H-xanthen-9-one (13e, 13h): Reaction

time 24 h, 82% yield when obtained from compound 5e; 2 h, 94%

when obtained from compound 5h; m.p. 231–233 °C. ¹H NMR

(500 MHz, [D₆]DMSO): δ = 6.68 (d, J = 8.7 Hz, 2 H, 3Ј,5Ј-H), 6.69 1.7 Hz, 1 H, 6-H), 7.98 (s, 1 H, 1-H), 8.22 (dd, J = 7.7, 1.7 Hz, 1

2658

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

New Polyhydroxylated 2,3-Diaryl-9H-xanthen-9-ones

H, 8-H), 8.95, 8.98 and 9.14 (3ϫs, 4 H, 3Ј,4Ј,3ЈЈ,4ЈЈ-OH) ppm. ¹³

NMR ([D₆]DMSO): δ = 115.4 and 115.5 (C-5Ј, C-5ЈЈ), 116.8 (C-

C

= 2.2 Hz, 1 H, 2ЈЈ-H), 6.65 (d, J = 8.2 Hz, 1 H, 5ЈЈ-H), 6.84 (dd, J

= 8.2, 0.6 Hz, 1 H, 7-H), 7.09 (d, J = 8.2 Hz, 1 H, 5-H), 7.17–7.20

2Ј, C-2ЈЈ), 118.3 (C-5), 118.9 (C-4), 119.4 (C-9a), 120.6 (C-6ЈЈ), (m, 2 H, 2Ј,6Ј-H), 7.28–7.36 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.54 (s, 1 H, 4-

120.7 (C-6Ј), 121.3 (C-8a), 124.4 (C-7), 126.1 (C-8), 127.0 (C-1), H), 7.75 (t, J = 8.2 Hz, 1 H, 6-H), 8.01 (s, 1 H, 1-H), 8.99 and 9.20

130.7 (C-1ЈЈ), 131.1 (C-1Ј), 135.5 (C-6), 136.8 (C-3), 144.5 (C-4ЈЈ),

144.9 (C-3Ј, C-3ЈЈ), 145.3 (C-4Ј), 147.6 (C-2), 154.3 (C-4a), 155.8 ([D₆]DMSO): δ = 107.4 (C-5), 108.4 (C-8a), 110.4 (C-7), 115.5 (C-

(2ϫbrs, 2 H, 3ЈЈ,4ЈЈ-OH), 12.59 (s, 1 H, 8-OH) ppm. ¹³C NMR

(C-4b), 175.8 (C-9) ppm. EI-MS: m/z (%) = 412 [M]^+·(79), 396

(17), 395 (16), 365 (15), 213 (26), 199 (17), 185 (30), 171 (25), 157

(20), 151 (18), 147 (17), 143 (22), 141 (17), 139 (19), 137 (22), 135

(20), 133 (20), 129 (43), 125 (31), 123 (31), 121 (30), 115 (23), 112

5ЈЈ), 116.9 (C-2ЈЈ), 118.3 (C-9a), 118.8 (C-4), 120.9 (C-6ЈЈ), 126.7

(C-1), 127.1 (C-4Ј), 128.3 (C-3Ј,5Ј), 129.3 (C-2Ј,6Ј), 130.1 (C-1ЈЈ),

136.7 (C-2), 137.5 (C-6), 139.8 (C-1Ј), 145.0 (C-3ЈЈ), 145.5 (C-4ЈЈ),

148.6 (C-3), 154.8 (C-4a), 155.9 (C-4b), 161.0 (C-8), 181.4 (C-

(32), 111 (60), 98 (96), 97 (89), 83 (100), 69 (30), 67 (33). HRMS 9) ppm. EI-MS: m/z (%) = 396 [M]^+·(100), 395 (7), 380 (9), 379

(EI): calcd. for C₂₅H₁₆O₆[M]^+·412.0947; found 412.0955.

(9), 349 (7). HRMS (EI): calcd. for C₂₅H₁₆O₅[M]^+·396.0998; found

396.1003.

6-Hydroxy-2,3-diphenyl-9H-xanthen-9-one (13m): Reaction time

1

1-Hydroxy-6,7-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one

(13r):

72 h, 37% yield. H NMR ([D₆]DMSO): δ = 6.91 (d, J = 2.1 Hz,

Reaction time 5 h, 90% yield; m.p. Ͼ 340 °C, dec. at 305 °C. ¹H

NMR ([D₆]DMSO): δ = 6.42 (dd, J = 8.0, 2.1 Hz, 1 H, 6Ј-H), 6.52

(dd, J = 8.2, 2.2 Hz, 1 H, 6ЈЈ-H), 6.60 (d, J = 2.1 Hz, 1 H, 2Ј-H),

6.65 (d, J = 2.2 Hz, 1 H, 2ЈЈ-H), 6.66 (d, J = 8.0 Hz, 1 H, 5Ј-H),

6.68 (d, J = 8.2 Hz, 1 H, 5ЈЈ-H), 6.84 (dd, J = 8.4, 0.7 Hz, 1 H, 7-

H), 7.09 (dd, J = 8.4, 0.7 Hz, 1 H, 5-H), 7.49 (s, 1 H, 4-H), 7.74 (t,

J = 8.4 Hz, 1 H, 6-H), 7.95 (s, 1 H, 1-H), 8.95 (s, 1 H, 4Ј-OH), 8.98

(s, 1 H, 4ЈЈ-OH), 9.00 and 9.17 (2ϫs, 2 H, 3Ј,3ЈЈ-OH), 12.63 (s, 1

H, 8-OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 107.4 (C-5), 108.4 (C-

8a), 110.3 (C-7), 115.46 and 115.53 (C-5Ј, C-5ЈЈ), 116.8 (C-2Ј, C-

2ЈЈ), 118.2 (C-9a), 118.7 (C-4), 120.5 (C-6Ј), 120.7 (C-6ЈЈ), 126.3

(C-1), 130.5 (C-1ЈЈ), 130.9 (C-1Ј), 137.0 (C-2), 137.4 (C-6), 144.6

(C-4Ј), 144.9 and 145.0 (C-3Ј, C-3ЈЈ), 145.4 (C-4ЈЈ), 148.5 (C-3),

154.4 (C-4a), 156.0 (C-4b), 161.0 (C-8), 181.5 (C-9) ppm. EI-MS:

m/z (%) = 428 [M]^+·(100), 396 (24), 381 (18), 213 (24), 191 (21),

185 (30), 129 (43), 125 (25), 123 (27), 121 (27), 115 (20), 112 (32),

111 (46), 107 (25), 105 (24), 98 (75), 97 (92), 95 (43), 85 (33), 83

(83), 81 (37), 73 (34), 71 (36), 67 (30). HRMS (EI): calcd. for

C₂₅H₁₆O₇[M]^+·428.0896; found 428.0888.

1 H, 5-H), 6.94 (dd, J = 8.7, 2.1 Hz, 1 H, 7-H), 7.13–7.16 (m, 2 H,

2Ј,6Ј-H), 7.20–7.23 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.26–7.31 (m, 6 H, 3Ј,4Ј,5Ј-

H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.63 (s, 1 H, 4-H), 8.07 (s, 1 H, 1-H), 8.08 (d, J

= 8.7 Hz, 1 H, 8-H), 11.04 (s, 1 H, 6-OH) ppm. ¹³C NMR ([D₆]

DMSO): δ = 102.8 (C-5), 114.1 (C-7), 114.3 (C-8a), 119.4 (C-4),

120.2 (C-9a), 127.0 (C-4Ј), 127.4 (C-1), 127.7 (C-4ЈЈ), 128.1 (C-8),

128.2 (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 129.4 (C-2ЈЈ,6ЈЈ), 129.5 (C-2Ј,6Ј), 136.4

(C-2), 139.3 (C-1ЈЈ), 139.7 (C-1Ј), 146.5 (C-3), 154.7 (C-4a), 157.8

(C-4b), 164.1 (C-6), 174.5 (C-9) ppm.

1-Hydroxy-6,7-diphenyl-9H-xanthen-9-one (12n, 13n): Reaction

time 1 h, 63% yield, see spectroscopic characterisation above. Also

occurs as a by-product in the synthesis of 1-hydroxy-6,7-diphenyl-

9H-xanthen-9-one (5n).

1-Hydroxy-7-(4-hydroxyphenyl)-6-phenyl-9H-xanthen-9-one (13o):

Reaction time 2 h, 90% yield; m.p. 130–133 °C. ¹H NMR ([D₆]-

DMSO): δ = 6.63 (d, J = 8.4 Hz, 2 H, 3Ј,5Ј-H), 6.79 (d, J = 8.4 Hz,

1 H, 7-H), 6.87 (d, J = 8.4 Hz, 2 H, 2Ј,6Ј-H), 7.00 (d, J = 8.3 Hz,

1 H, 5-H), 7.15–7.18 (m, 2 H, 2ЈЈ,6ЈЈ-H), 7.29–7.31 (m, 3 H,

3ЈЈ,4ЈЈ,5ЈЈ-H), 7.49 (s, 1 H, 4-H), 7.70 (dd, J = 8.4, 8.3 Hz, 1 H, 6-

H), 7.91 (s, 1 H, 1-H), 12.49 (s, 1 H, 8-OH) ppm. ¹³C NMR ([D₆]

DMSO): δ = 107.6 (C-5), 108.6 (C-8a), 110.6 (C-7), 115.4 (C-3Ј,5Ј),

118.9 (C-9a), 119.5 (C-4), 126.5 (C-1), 128.1 (C-4ЈЈ), 128.5 (C-

3ЈЈ,5ЈЈ), 129.6 (C-2ЈЈ,6ЈЈ), 130.1 (C-1Ј), 130.9 (C-2Ј,6Ј), 137.1 (C-2),

137.8 (C-6), 139.6 (C-1ЈЈ), 148.2 (C-3), 154.6 (C-4a), 156.1 (C-4b),

156.8 (C-4Ј), 161.2 (C-8), 181.6 (C-9) ppm. EI-MS: m/z (%) = 380

[M]^+·(100), 379 (20), 351 (6). HRMS (EI): calcd. for C₂₅H₁₆O₄

[M]^+·380.1049; found 380.1046.

1,3-Dihydroxy-6,7-diphenyl-9H-xanthen-9-one (13s): Reaction time

1

120 h, 60% yield. H NMR ([D₆]DMSO): δ = 6.24 (d, J = 1.9 Hz,

1 H, 7-H), 6.43 (d, J = 1.9 Hz, 1 H, 5-H), 7.13–7.31 (m, 10 H, 2,3-

C₆H₅), 7.61 (s, 1 H, 4-H), 8.02 (s, 1 H, 1-H), 11.23 (brs, 1 H, 6-

OH), 12.80 (s, 1 H, 8-OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 94.3

(C-5), 98.3 (C-7), 102.4 (C-8a), 118.9 (C-4), 119.2 (C-9a), 126.6 (C-

1), 127.2 (C-4Ј), 127.9 (C-4ЈЈ), 128.3 (C-3Ј,5Ј, C-3ЈЈ,5ЈЈ), 129.5 (C-

2ЈЈ,6ЈЈ), 129.6 (C-2Ј,6Ј), 136.6 (C-2), 139.2 (C-1ЈЈ), 139.5 (C-1Ј),

147.3 (C-3), 154.5 (C-4a), 157.6 (C-4b), 162.9 (C-8), 166.0 (C-6),

179.4 (C-9) ppm. EI-MS: m/z (%) = 380 [M]^+·(100), 379 (35), 365

(7), 228 (5), 84 (10), 66 (11). HRMS (EI): calcd. for C₂₅H₁₆O₄

[M]^+·380.1049; found 380.1045.

7-(3,4-Dihydroxyphenyl)-1-hydroxy-6-phenyl-9H-xanthen-9-one

(13p): Reaction time 3 h, 83% yield; m.p. 222–224 °C. ¹H NMR

([D₆]DMSO): δ = 6.32 (dd, J = 8.1, 2.1 Hz, 1 H, 6Ј-H), 6.54 (d, J

= 2.1 Hz, 1 H, 2Ј-H), 6.60 (d, J = 8.1 Hz, 1 H, 5Ј-H), 6.79 (d, J =

8.3 Hz, 1 H, 7-H), 7.01 (d, J = 8.3 Hz, 1 H, 5-H), 7.17–7.20 (m, 2

H, 2ЈЈ,6ЈЈ-H), 7.30–7.32 (m, 3 H, 3ЈЈ,4ЈЈ,5ЈЈ-H), 7.48 (s, 1 H, 4-H),

7.70 (t, J = 8.3 Hz, 1 H, 6-H), 7.91 (s, 1 H, 1-H), 12.48 (s, 1 H, 8-

OH) ppm. ¹³C NMR ([D₆]DMSO): δ = 107.8 (C-5), 108.7 (C-8a),

110.7 (C-7), 115.8 (C-5Ј), 117.3 (C-2Ј), 118.9 (C-9a), 119.6 (C-4),

121.2 (C-6Ј), 126.6 (C-1), 128.3 (C-4ЈЈ), 128.7 (C-3ЈЈ,5ЈЈ), 129.6 (C-

2ЈЈ,6ЈЈ), 130.9 (C-1Ј), 137.4 (C-2), 138.0 (C-6), 139.7 (C-1ЈЈ), 145.0

(C-4Ј), 145.3 (C-3Ј), 148.3 (C-3), 154.7 (C-4a), 156.2 (C-4b), 161.2

(C-8), 181.7 (C-9) ppm. EI-MS: m/z (%) = 396 [M]^+·(100), 380

(15), 379 (15), 349 (16), 213 (27), 199 (18), 185 (19), 171 (24), 157

(20), 147 (40), 143 (25), 137 (28), 129 (40), 125 (32), 123 (29), 121

(34), 111 (48), 98 (77), 97 (98), 96 (45), 95 (53), 85 (36), 83 (77), 81

(47), 73 (40), 67 (29). HRMS (EI): calcd. for C₂₅H₁₆O₅[M]^+·

396.0998; found 396.0996.

Acknowledgments

Sincere thanks are expressed to the University of Aveiro, Fundação

para a Ciência e a Tecnologia (FCT), and Fundo Europeu de De-

senvolvimento Regional (FEDER) for funding the Organic Chem-

istry Research Unit and the project POCI/QUI/59284/2004. One of

us (C. M. M. S.) is also grateful to Programa de Desenvolvimento

Educativo para Portugal (PRODEP 5.3) for financial support.

[1] J. C. Roberts, Chem. Rev. 1961, 38, 591–605.

[2] L. M. M. Vieira, A. Kijjoa, Curr. Med. Chem. 2005, 12, 2413–

2446.

[3] G. J. Bennett, H.-H. Lee, Phytochemistry 1989, 28, 967–998.

[4] S. Sakai, M. Katsura, H. Takayama, N. Aimi, N. Choke-

thaworn, M. Suttajit, Chem. Pharm. Bull. 1993, 41, 958–960.

[5] I. Fukawa, H. Yoneda, K. K. K. K. Asahi, European Patent

EP0237004, Sep, 1987.

6-(3,4-Dihydroxyphenyl)-1-hydroxy-7-phenyl-9H-xanthen-9-one

(13q): Reaction time 3 h, 71% yield; m.p. 205–207 °C. ¹H NMR

([D₆]DMSO): δ = 6.47 (dd, J = 8.2, 2.2 Hz, 1 H, 6ЈЈ-H), 6.61 (d, J

Eur. J. Org. Chem. 2009, 2642–2660

www.eurjoc.org

2659

C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro

FULL PAPER

[6]

[7]

[8]

[9]

[18] A.-E. Hay, M.-C. Aumond, S. Mallet, V. Dumontet, M. Litau-

don, D. Rondeau, P. Richomme, J. Nat. Prod. 2004, 67, 707–

709.

[19] P. M. Pauletti, I. Castro-Gamboa, D. H. S. Silva, M. C. M.

Young, D. M. Tomazela, M. N. Eberlin, V. S. Bolzani, J. Nat.

Prod. 2003, 66, 1384–1387.

[20] M. M. M. Pinto, M. E. Sousa, M. S. J. Nascimento, Curr. Med.

Chem. 2005, 12, 2517–2538.

[21] W. Bors, W. Heller, C. Michel, K. Stettmaier, in: Handbook of

Antioxidants (Ed.: E. Cadenas, L. Packer), Marcel

Dekker, Inc., New York, 1996, pp. 409–466.

[22] M. E. Sousa, M. M. M. Pinto, Curr. Med. Chem. 2005, 12,

2447–2479.

A. S. Kelkar, R. M. Letcher, K.-K. Cheung, K.-F. Chiu, G. D.

Brown, J. Chem. Soc. Perkin Trans. 1 2000, 3732–3741.

A. Abdel-Lateff, C. Klemke, G. M. König, A. D. Wright, J.

Nat. Prod. 2003, 66, 706–708.

T. Fukai, M. Yonekawa, A.-J. Hou, T. Nomura, H.-D. Sun, J.

Uno, J. Nat. Prod. 2003, 66, 1118–1120.

M. M. Mackeen, A. M. Ali, N. H. Lajis, K. Kawazu, Z. Has-

san, M. Amran, M. Habsah, L. Y. Mooi, S. M. Mohamed, J.

Ethnopharmacol. 2000, 72, 395–402.

H. H. Park, Y.-D. Park, J.-M. Han, K.-R. Im, B. W. Lee, I. Y.

Jeong, T.-S. Jeong, W. S. Lee, Bioorg. Med. Chem. Lett. 2006,

16, 5580–5583.

[10]

[23] L. K. Cassilas, C. A. Townsend, J. Org. Chem. 1999, 64, 4050–

[11]

C. N. Lin, M. I. Chung, S. J. Liou, T. H. Lee, J. P. Wang, J.

Pharm. Pharmacol. 1996, 48, 532–538.

4059.

[24] M. Afzal, J. M. Al-Hassan, Heterocycles 1980, 14, 1173–1205.

[25] S. S. Ibrahim, Ind. Eng. Chem. Res. 2001, 40, 37–39.

[26] C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro, Synlett

2005, 3095–3098.

[27] C. M. M. Santos, A. M. S. Silva, J. A. S. Cavaleiro, Synlett

2007, 3113–3116.

[28] A. M. S. Silva, D. C. G. A. Pinto, J. A. S. Cavaleiro, A. Lévai,

T. Patonay, Arkivoc 2004, 6, 106–123.

[29] A. Fougerousse, E. Gonzalez, R. Brouillard, J. Org. Chem.

2000, 65, 583–586.

[30] S. Punna, U. H. Meunier, M. G. Finn, Org. Lett. 2004, 6, 2777–

2779.

[31] T. Nordvik, U. H. Brinker, J. Org. Chem. 2003, 68, 9394–9399.

[32] D. C. G. A. Pinto, A. M. S. Silva, L. M. P. M. Almeida, J. A. S.

Cavaleiro, A. Lévai, T. Patonay, J. Heterocycl. Chem. 1998, 35,

217–224.

[12] M. Riscoe, J. X. Kelly, R. Winter, Curr. Med. Chem. 2005, 12,

2539–2549.

[13] C. Portela, C. M. M. Afonso, M. M. M. Pinto, M. J. Ramos,

Bioorg. Med. Chem. 2004, 12, 3313–3321.

[14] V. K. Dua, V. P. Ojha, R. Roy, B. C. Joshi, N. Valecha, C. U.

Devi, M. C. Batnagar, V. P. Sharma, S. K. Subbarao, J. Ethno-

pharmacol. 2004, 95, 247–251.

[15] H.-Z. Zhang, S. Kasibhatla, Y. Wang, J. Herich, J. Guastella,

B. Tseng, J. Drewe, S. X. Cai, Bioorg. Med. Chem. 2004, 12,

309–317.

[16] G. W. Rewcastle, G. J. Atwell, L. Zhang, B. C. Baguley, W. A.

Denny, J. Med. Chem. 1991, 34, 217–222.

[17] J. Merza, M.-C. Aumond, D. Rondeau, V. Dumontet, A.-M.

Le Ray, D. Séraphin, P. Richomme, Phytochemistry 2004, 65,

2915–2920.

Received: January 10, 2009

Published Online: April 15, 2009

2660

www.eurjoc.org

Eur. J. Org. Chem. 2009, 2642–2660

Article Doi

Efficient syntheses of new polyhydroxylated 2,3-diaryl-9H-xanthen-9-ones

DOI: 10.1002/ejoc.200900026

Source and publish data:

Authors:

Article abstract of DOI:10.1002/ejoc.200900026

Full text of DOI:10.1002/ejoc.200900026

Products guided by the article

R&D Labs maybe for 1172141-19-3

Relevant to this article

Hot Product