Efficient RuIII-catalyzed synthesis of 9-aryl-9H-xanthene-3,6- diols as precursors to fluorones

Article abstract of DOI:10.1016/j.cclet.2011.11.012

Efficient condensation of resorcinol and various aromatic aldehydes in the presence of RuCl₃·nH₂O as a homogeneous catalyst under reflux conditions was investigated. It was found that a very simple method afforded good to excellent y

Full text of DOI:10.1016/j.cclet.2011.11.012

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Chinese Chemical Letters 23 (2012) 165–168
www.elsevier.com/locate/cclet
Efficient RuIII-catalyzed synthesis of 9-aryl-9H-xanthene-3,6-diols
as precursors to fluorones
*
Khalil Tabatabaeian , Alireza Khorshidi, Ali Dadashi, Milad Khoshnood
Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Iran
Received 24 August 2011
Available online 22 December 2011
Abstract
Efficient condensation of resorcinol and various aromatic aldehydes in the presence of RuCl3ÁnH2O as a homogeneous catalyst
under reflux conditions was investigated. It was found that a very simple method afforded good to excellent yields of the desired
products.
# 2011 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
Keywords: Aldehyde; Resorcinol; Ruthenium; Xanthenediol; Fluorone
There has been tremendous interest to develop xanthene derivatives synthesis due to their biological activities such
as antibacterial, antiviral and anti-inflammatory [1]. These heterocyclic compounds are also utilized as dyes [2].
Fluorone, fluorescein, rosamine and rhodamine are common xanthene dyes. Xanthene dyes are extracted from soil and
plants such as Indigofera longeracemosa [3]. Daidzein and formonenetin which belong to the soy isoflavones, as
bioactive compounds was obtained from resorcinol [4]. On the other hand, synthesis of fluorone derivatives has
attracted considerable attention because they have found numerous applications [5–11]. Thermal and acid-catalyzed
condensation of resorcinol with aldehydes and then oxidation of leuco base is one of the straightforward approaches
for the synthesis of fluorone [12–16]. In this research we aimed at the synthesis of xanthenediols, which may be
susceptible to further oxidation to fluorones.
Organic syntheses promoted by a catalyst, is our prime interest [17–19]. Recently, we have been involved in the
study of the catalytic activity of ruthenium towards organic reactions such as oxidation of aromatic and heteroaromatic
compounds [20], double-conjugate 1,4-addition to enones [21], nucleophilic addition to epoxides [22], Michael
addition of indoles to hormone steroids [23], condensation of b-naphthol with aldehydes [24] and three-component
cyclocondensation of b-naphthol, aldehydes, and 5,5-dimethylcyclohexane-1,3-dione (dimedone) [25]. As a matter of
fact, many organic transformations, which involve ruthenium species as catalyst, are known and well-documented
[26,27].
Herein, we report a convenient method for the synthesis of 9-aryl-9H-xanthene-3,6-diols as precursors for fluorone
dyes from condensation of resorcinol and aldehydes in the presence of RuCl3ÁnH2O as a homogeneous catalyst
(Scheme 1).
* Corresponding author.
E-mail address: Taba@guilan.ac.ir (K. Tabatabaeian).
1001-8417/$ – see front matter # 2011 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2011.11.012

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K. Tabatabaeian et al. / Chinese Chemical Letters 23 (2012) 165–168
R
OH
CHO
RuCl3.nH2O (5 mol%)
MeOH, 80 oC, 40-80 min
2
HO
O
OH
OH
R
1
2a-2j
3a-3j
2a: R= H, 2b: R= 4-NO2, 2c: R= 4-Cl, 2d: R= 4-Br, 2e: R= 4-OH, 2f: R= 4-OCH3,
2g: R= 4-OH, 3-OCH3, 2h: R= 2-OH, 3-OCH3, 2i: 3,4-OCH3, 2j: R= 4-SCH3
Scheme 1. Double condensation of resorcinol and aromatic aldehydes.
1. Experimental
1
All products were characterized by physical data (mp), spectral data (IR, H NMR) and elemental analysis.
¨
Uncorrected melting points were measured by a BUCHI melting point B-540 apparatus. IR spectra were carried out on
1
a Shimadzu FTIR-8400S spectrophotometer. H NMR spectra were recorded at ambient probe temperature on a
1
Bruker DRX-400 Avance spectrometer. Chemical shifts of H NMR spectra were reported in ppm downfield from
TMS as internal standard and coupling constants (J) were expressed in hertz. Thin layer chromatography (TLC) was
performed on Silica gel 60 F plates eluting with petroleum ether–ethyl acetate, 10:3. Elemental analyses were
performed on a Carlo-Erba EA1110 CNNO-S analyzer and agreed with the calculated values. Resorcinol, aldehydes,
RuCl3ÁnH2O and solvents were purchased from Merck and used without further purification.
To a mixture of resorcinol (220.2 mg, 2 mmol) and benzaldehyde (106.1 mg, 1 mmol) in methanol (5 mL),
RuCl3ÁnH2O (10.7 mg, 0.05 mmol) was added. The resulting mixture was then refluxed in an oil bath at 80 8C for
50 min. The progress of the reaction was monitored by TLC. After completion of the reaction, as indicated by TLC, the
reaction mixture was cooled at room temperature, the precipitate was filtered off and washed with cold methanol. The
solid was dried under vacuum to afford the desired compound in pure form (261.3 mg, 90%). The same procedure was
also used for the other products listed in Table 1.
1.1. 9-Phenyl-9H-xanthene-3,6-diol (3a)
Solid; mp: 170–172 8C, IR (KBr): n (cmÀ1); 3380, 3010, 1615, 1520, 1490, 1420, 1280, 1080, 915, 835, 745; 1H
NMR (400 MHz, DMSO-d6, 25 8C): d 7.21 (t, 2H, J = 7.6 Hz), 7.11 (t, 1H, J = 7.6 Hz), 7.04 (d, 2H, J = 7.6 Hz), 6.85
(d, 2H, J = 8.4 Hz), 6.41 (d, 2H, J = 8.4 Hz), 6.30 (s, 2H), 5.52 (s, 1H), 5.21 (s, 2H). Anal. calcd. for C19H14O3: C,
78.61; H, 4.86. Found: C, 78.65; H, 4.87.
Supplementary data are also available for the other products listed in Table 1.
2. Results and discussion
Typical results for the ruthenium-catalyzed condensation of resorcinol with aromatic aldehydes are shown in Table
1 and indicate the scope of the reaction. In an optimized procedure (as it is outlined in Scheme 1), treatment of
resorcinol (2 mmol) with benzaldehyde (1 mmol) in the presence of RuCl3ÁnH2O (5 mol%) in methanol (5 mL) at
80 8C for 50 min gave 9-phenyl-9H-xanthene-3,6-diol in 90% yield as a solid precipitate (Table 1, entry 1).
From the NMR spectral data, it was revealed that the reaction leads to the selective functionalization of resorcinol at
C-6 rather than both at C-2 and C-6.
Various aromatic aldehydes bearing electron-withdrawing or electron-releasing groups were used and resulted in
good to excellent yields of the desired products within 40–80 min (75–94%) without formation of any side products. It
was shown that aromatic aldehydes with electron-withdrawing groups reacted faster than those bearing electron-
donating groups and higher yields of product were obtained. The unique feature of the reaction is that corresponding 9-
aryl-9H-xanthene-3,6-diol derivatives are insoluble in the reaction solvent and this leads to an easy workup (see
Section 1). With regard to the aliphatic aldehydes, however, the present protocol resulted in trace yields of products.

K. Tabatabaeian et al. / Chinese Chemical Letters 23 (2012) 165–168
167
Table 1
RuCl3ÁnH2O catalyzed synthesis of 9-aryl-9H-xanthene-3,6-diol derivatives.
Entry
Aldehyde
Time (min)
Product
Yield (%)a
90
Mp (8C)
1
50
3a
170–172
CHO
2a
2
3
4
5
6
7
40
45
40
60
65
70
3b
3c
3d
3e
3f
92
90
94
84
84
82
316–318
288–290
310–312
131–133
200–202
218–220
O2N
Cl
CHO
2b
CHO
CHO
2c
Br
2d
HO
CHO
2e
H3CO
CHO
2f
3g
HO
CHO
H3CO
2g
8
80
65
60
3h
3i
75
80
84
214–216
226–228
206–208
CHO
OH
H3CO
2h
9
H3CO
H3CO
CHO
2i
2j
10
3j
H3CS
CHO
Note: All products were characterized by 1H NMR and IR data.
a
Isolated yields.
OH
OH
OH
OH
H
O
R
OH
H
OH
H
Ru
Ru
R
O
R
H
O
I
Ru
H
OH
O
Ru
R
H
OH
R
H
:
Ru
OH
HO
OH
HO
OH
OH OH
HO
O
OH
OH
-H2O
HO
OH
H2O
H
R
H
R
H
R
H
9-aryl-9H-xanthene-3,6-diol
II
III
Scheme 2. Plausible mechanism for the synthesis of 9-aryl-9H-xanthene-3,6-diol in the presence of RuCl3ÁnH2O as catalyst.

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K. Tabatabaeian et al. / Chinese Chemical Letters 23 (2012) 165–168
A plausible mechanism for this transformation under ruthenium catalysis is outlined in Scheme 2. As it is shown,
prior activation of the carbonyl group of aldehyde by RuIII to give (I) and then two successive nucleophilic attacks from
two resorcinol molecules gives intermediate II. After loss of one molecule of water to give intermediate III,
dehydration results in the desired product.
3. Conclusion
The present protocol provides a powerful and convenient method for the preparation of 9-aryl-9H-xanthene-3,6-
diol derivatives. This method is endowed with several merits namely, simplicity in operation, mild reaction conditions,
high yields of products and low catalyst loading.
Acknowledgment
We are grateful to the Research Council of University of Guilan for their partial support.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.cclet.
2011.11.012.
References
[1] J.R. Dimmock, S.K. Raghavan, G.E. Bigam, Eur. J. Med. Chem. 23 (1988) 111.
[2] A. Banerjee, A.K. Mukherjee, Stain Technol. 56 (1981) 83.
[3] J.P. Alcantara-Licudine, M.K. Kawate, Q.X. Li, J. Agric. Food Chem. 45 (1997) 766.
[4] S.R. Li, P.Y. Chen, L.Y. Chen, et al. Tetrahedron Lett. 50 (2009) 2121.
[5] M.Y. Mizutani, A. Itai, J. Med. Chem. 47 (2004) 4818.
[6] W. Wang, J.O. Escobedo, C.M. Lawrence, et al. J. Am. Chem. Soc. 126 (2004) 3400.
[7] K.R. Gee, Z.L. Zhou, W.J. Qian, et al. J. Am. Chem. Soc. 124 (2002) 776.
[8] J.R. Blattner, L. He, J.J. Lemasters, Anal. Biochem. 295 (2001) 220.
[9] Z. Li, J. Pan, J. Tang, Analyst 126 (2001) 1154.
[10] S. Liu, Y. Xie, G. Yong, et al. J. Agric. Food Chem. 48 (2000) 5860.
[11] T. Hirano, K. Kikuchi, Y. Urano, et al. Angew. Chem. Int. Ed. 39 (2000) 1052.
[12] J. Shi, X. Zhang, D.C. Neckers, J. Org. Chem. 57 (1992) 4418.
[13] V.V. Martin, A. Rothe, Z. Diwu, et al. Bioorg. Med. Chem. Lett. 14 (2004) 5313.
[14] Y. Yang, J.O. Escobedo, A. Wong, et al. J. Org. Chem. 70 (2005) 6907.
[15] J.P. Bacci, A.M. Kearney, D.L. Van Vranken, J. Org. Chem. 70 (2005) 9051.
[16] Q. He, E.W. Miller, A.P. Wong, C.J. Chang, J. Am. Chem. Soc. 128 (2006) 9316.
[17] L. Zare, N.O. Mahmoodi, A. Yahyazadeh, et al. Chin. Chem. Lett. 21 (2010) 538.
[18] S. Zarrabi, N.O. Mahmoodi, K. Tabatabaeian, et al. Chin. Chem. Lett. 20 (2009) 1400.
[19] N.O. Mahmoodi, K. Tabatabaeian, M. Kosari, et al. Chin. Chem. Lett. 19 (2008) 1431.
[20] K. Tabatabaeian, M. Mamaghani, N.O. Mahmoodi, et al. Catal. Commun. 9 (2008) 416.
[21] K. Tabatabaeian, M. Mamaghani, N.O. Mahmoodi, et al. J. Mol. Catal. A: Chem. 270 (2007) 112.
[22] K. Tabatabaeian, M. Mamaghani, N.O. Mahmoodi, et al. Tetrahedron Lett. 49 (2008) 1450.
[23] K. Tabatabaeian, M. Mamaghani, N.O. Mahmoodi, et al. Synth. Commun. 40 (2010) 1677.
[24] K. Tabatabaeian, A. Khorshidi, M. Mamaghani, et al. Synth. Commun. 41 (2011) 1427.
[25] K. Tabatabaeian, A. Khorshidi, M. Mamaghani, et al. Can. J. Chem. 89 (2011) 623.
[26] S.I. Murahashi, Ruthenium in Organic Synthesis, Wiley-VCH, New York, 2004.
[27] C. Bruneau, P.H. Dixneuf, Ruthenium Catalysts and Fine Chemistry, Springer, Berlin, 2004.