Sc[N(SO2C8F17)2]3 catalyzed condensation of β-naphthol and aldehydes in fluorous solvent: One-pot synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes

Article abstract of DOI:10.1016/j.jfluchem.2009.06.013

A facile synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes was proposed by one-pot condensation of β-naphthol with aryl or alkyl aldehydes by using Scandium bis(perfluorooctanesulfonyl)imide complex as catalyst and perfluorodecalin as sole solvent.

Full text of DOI:10.1016/j.jfluchem.2009.06.013

Journal of Fluorine Chemistry 130 (2009) 989–992
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Short communication
Sc[N(SO2C8F17)2]3 catalyzed condensation of
b-naphthol and aldehydes in
fluorous solvent: One-pot synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes
*
Mei Hong, Chun Cai
College of Chemical Engineering, Nanjing University of Science and Technology, Xiao Ling Wei Street, No. 200, Nanjing 210094, People’s Republic of China
A R T I C L E I N F O
A B S T R A C T
Article history:
A facile synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes was proposed by one-pot condensation
Received 20 April 2009
Received in revised form 19 June 2009
Accepted 22 June 2009
Available online 27 June 2009
of
b-naphthol with aryl or alkyl aldehydes by using Scandium bis(perfluorooctanesulfonyl)imide
complex as catalyst and perfluorodecalin as sole solvent.
ß 2009 Elsevier B.V. All rights reserved.
Keywords:
Xanthene
Fluorous solvent
Bis(perfluorooctanesulfonyl)imide
Scandium complex
1. Introduction
omethanesulfonates. Moreover, they are water-repellent due to
highly ‘‘fluorous’’ nature brought about by the perfluoroalkyl
chains surrounding the central metal. It is also noted that
perfluorocarbon solvents have some unique properties which
make them attractive alternatives for conventional organic
solvents [19]. In this work we report a mild and effective method
for the preparation of aryl or alkyl-14H-dibenzo[a,j]xanthenes
using Sc[N(SO2C8F17)2]3 complex as catalyst in fluorous biphase
system. It was found that under mild conditions the catalyst can
function efficiently at low catalytic loadings (1 mol%) and can be
easily recovered and reused.
Xanthenes, especially benzoxanthenes, have drawn much
attention in the field of medicinal chemistry. These oxygen-
containing heterocycles have been reported to exert various
biological and therapeutic properties in antibacterial [1], antiviral
[2], and anti-inflammatory activities [3], as well as in photo-
dynamic therapy (PDT) [4]. Furthermore, they are used as dyes [5],
or as fluorescent materials for the visualization of biomolecular
assemblies [6]. Their application is also found in laser technologies
[7].
The synthesis of benzoxanthenes has been achieved by various
methods [8]. Among them, condensation of
b-naphthol with
2. Results and discussion
aldehydes has been explored using different catalysts such as
sulfamic acid [9], p-TSA [10], selectfluorTM [11], I2 [12], silica
sulfuric acid [13] and Yb(OTf)3 [14]. However, these catalyst
systems suffer from some limitation such as long reaction time,
high catalyst loadings, use of toxic solvent or special apparatus. The
search for milder and more environmentally benign conditions is,
therefore, highly demanding for the synthesis of these compounds.
Metal (e.g. Sn, Sc and Yb) complexes with bis(perfluoroocta-
nesulfonyl)imide ligands are active and recyclable catalysts in the
fluorous immobilized phase for Baeyer–Villiger oxidation [15],
Diels–Alder reaction [16], esterification [17] and Friedel–Crafts
acylation [18], far superior to the corresponding metal trifluor-
As a model reaction we chose condensation of benzaldehyde
and
b-naphthol catalyzed by Sc[N(SO2C8F17)2]3 complex in
different solvent systems. As shown in Table 1, the highest yield
(93%) was achieved when the reaction was conducted in
perfluorodecalin (C10F18, cis- and trans-mixture) as a sole solvent
at 110 8C for 5 h (Table 1, entry 8). In order to make the reaction
more accessable, we explored different co-solvent systems taking a
common general organic solvent. Unfortunately, the use of co-
solvent system resulted in lower product yield under the similar
conditions (Table 1, entries 1–7). Among the co-solvents studied,
toluene was proved to be efficient (Table 1, entry 3) in terms of its
relatively higher yield. Although the reasons why the use of co-
solvent such as toluene decreases the product yield are not clear,
we assumed that difference in solubility of the catalyst and the
substrate in perfluorodecalin or in toluene would have an influence
* Corresponding author. Tel.: +86 25 84315514; fax: +86 25 84315030.
E-mail address: c.cai@mail.njust.edu.cn (C. Cai).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.06.013

990
M. Hong, C. Cai / Journal of Fluorine Chemistry 130 (2009) 989–992
Scheme 1. Synthesis of 14-substituted-14H-dibenzo[a,j]xanthenes.
Table 1
Table 3
Effect of co-solvents on the condensationa.
Synthesis of 14-substitued-14H-dibenzo[a,j]xanthenesa.
Entry
Co-solvent
Time (h)
Yield (%)b
Entry
RCHO (1)
Time (h)
Product
Yield (%)b
1
2
3
4
5
6
7
8
ClCH2CH2Cl
MeCN
PhMe
EtOH
6
6
6
6
6
6
6
5
75
23
81
67
52
64
20
93
1
2
2-ClC6H4 (1a)
4-ClC6H4 (1b)
2,4-Cl2C6H3 (1c)
3-NO2C6H4 (1d)
4-NO2C6H4 (1e)
4-HOC6H4 (1f)
C6H5 (1g)
2.5
2
3a
3b
3c
3d
3e
3f
91
96
95
90
95
94
93
85
91
75
70
3
2
4
3
MeOH
Dioxane
THF
5
2
6
2
7
5
3g
3h
3i
–
8
4-MeOC6H4 (1h)
4-MeC6H4 (1i)
CH3CH2 (1j)
6
9
5.5
7
a
Reaction conditions: benzaldehyde (1 mmol),
b
-naphthol (2 mmol),
10
11
3j
Sc[N(SO2C8F17)2]3 (0.01 mmol), perfluorodecalin (1.5 mL), co-solvent (2 mL),
CH3CH2CH2 (1k)
7
3k
110 8C or refluxing.
b
a
Isolated yields.
Reaction
conditions:
aldehyde
(1 mmol),
b
-naphthol
(2 mmol),
Sc[N(SO2C8F17)2]3 (0.01 mmol), 110 8C.
b
Isolated yields.
on their effective miscibility. Based on these results, we employed
only perfluorodecalin as sole solvent in the further experiments.
We then investigated the catalytic activity of different rare
earth bis(perfluorooctanesulfonyl)imide complexes in the model
reaction. The results are summarized in Table 2. It was found that
several metal bis(perfluorooctanesulfonyl)imide complexes gave
promising results. Especially, Sc[N(SO2C8F17)2]3 was found to be
the most effective catalyst (Table 2, entry 4) based on the product
yield. The catalyst system is proved again to be important since the
reaction hardly proceeded without catalyst and fluorous solvent
(yield less than 5%).
The possibility of multi-use of Sc[N(SO2C8F17 2 3
) ] catalyst for the
synthesis of phenylderivative was also investigated. After separa-
tion of the product, fluorous phase containing the catalyst was
reused for the next cycle. As shown in Table 2, even after
Sc[N(SO2C8F17)2]3 catalyst was recycled five times, almost same
isolated yield of the final product was realized.
3. Conclusion
Next, we examined the condersation of
b
-naphthol with
In conclusion, a simple and efficient method for the synthesis of
various aldehydes in the presence of Sc[N(SO2C8F17)2]3 in
perfluorodecalin at 110 8C (Scheme 1). As listed in Table 3, in all
cases the corresponding benzoxanthenes were obtained in good
yields (70–96%) after 2–7 h. It was found that the nature of the
substituent on the aromatic ring had a magnificent effect on the
reaction rate. Generally, aromatic aldehydes with electron with-
drawing group showed increased reaction rate (Table 3, entries 1–
5). Interestingly, 4-hydroxybenzaldehyde also gave the desired
product within a short reaction time in excellent yield (Table 3,
entry 6). On the other hand, reactions with aliphatic aldehydes
provided somewhat lower yields than those with aromatic
aldehydes (Table 3, entries 10 and 11).
14-substituted-14H-dibenzo[a,j]xanthenes has been developed
via condensation of
b-naphthol with aldehydes catalyzed by
Sc[N(SO2C8F17)2]3 complex in perfluorodecalin as a sole solvent.
The attractive features of this protocol are its generality, easy
work-up, and catalyst reusability.
4. Experimental
4.1. General
Melting points were obtained with Shimadzu DSC-50 thermal
analyzer. Inductively coupled plasma (ICP) spectra were measured
on Ultima2C apparatus. Elemental analyses were performed on a
Yanagimoto MT3CHN recorder. IR spectra were recorded on a
Bomem MB 154S infrared analyzer. 1H NMR and 19F NMR spectra
were recorded with Bruker Advance RX500. The perfluorodecalin
and rare earth salts were purchased from Aldrich Co. Commercially
available reagents were used without further purification.
Table 2
Effect of various catalysts on the condensationa.
Entry
Catalyst
Yield (%)b
1
2
3
4
5
6
7
8
9
Sn[N(SO2C8F17)2]4
Hf[N(SO2C8F17)2]4
Yb[N(SO2C8F17)2]3
Sc[N(SO2C8F17)2]3
Y[N(SO2C8F17)2]3
Sm[N(SO2C8F17)2]3
Eu[N(SO2C8F17)2]3
Td[N(SO2C8F17)2]3
Dy[N(SO2C8F17)2]3
75
82
4.2. Preparation of (C8F17SO2)2NH and Sc[N(SO2C8F17)2]3
90
93, 90, 92, 93, 92c
72
53
80
32
57
4.2.1. Preparation of (C8F17SO2)2NH
(C8F17SO2)2NH was prepared according to the literature [20,21].
Ammonia was added into perfluorooctanesulfonyl fluoride (36.7 g,
73 mmol) at À20 8C. After the stirring was held at À20 8C for about
1 h, it was then continued at room temperature for another 1 h. The
solid product was acidified with 2 M HCl followed by addition of
Et2O. The organic layer was dried over anhydrous Na2SO4 and
concentrated under reduced pressure, dried in vacuum to give
a
Reaction conditions: benzaldehyde (1 mmol),
b-naphthol (2 mmol), catalyst
(0.01 mmol), perfluorodecalin (1.5 mL), 110 8C, 5 h.
b
Isolated yields.
c
Catalyst was reused for five times.

M. Hong, C. Cai / Journal of Fluorine Chemistry 130 (2009) 989–992
991
C8F17SO2NH2 (87% yield). Then the mixture of perfluorooctanesul-
fonyl fluoride (36.0 g, 72 mmol), perfluorooctanesulfonamide
(34.4 g, 69 mmol) and Et3N (60 mL) was heated at reflux for 23 h.
The lower brown fluorous layer was washed with 10% HCl and dried
in vacuum to afford (C8F17SO2)2N HNEt3. Free (C8F17SO2)2NH was
obtained through acidic ion exchange resin column in 50% yield.
Anal. Calcd. for (C8F17SO2)2NH: C, 19.58; N, 1.43; H, 0.10. Found: C,
6.59 (s, 1H), 7.03 (t, J = 7.8 Hz, 2H), 7.40–7.56 (m, 6H), 7.66–7.72
(m, 4H), 8.30–8.46 (m, 4H).
4.3.6. 14-(4-Hydroxyphenyl)-14H-dibenzo[a,j]xanthene (3f)
Pink solid; mp 138–140 8C (140 8C, Ref. [12]). IR (KBr)
1592, 1511, 1401, 1250, 1242, 816 cmÀ1 1H NMR (CDCl3,
500 MHz) : 4.98 (s, 1H), 6.42 (s, 1H), 6.58 (d, J = 8.4 Hz, 2H),
y 3404,
.
d
19.61; N, 1.45; H, 0.16. 19F NMR:
d
À126.2, À121.8, À114.0, À81.2.
7.38 (t, J = 10.8 Hz, 2H), 7.43 (d, J = 7.5 Hz, 2H), 7.48 (d, J = 8.9, 2H),
7.58 (t, J = 7.4 Hz, 2H), 7.79 (d, J = 5.1 Hz, 2H), 7.83 (d, J = 8.1 Hz,
2H), 8.39 (d, J = 8.4 Hz, 2H).
4.2.2. Preparation of Sc[N(SO2C8F17)2]3
Scandium bis(perfluorooctanesulfonyl)imide
complex,
Sc[N(SO2C8F17)2]3 was prepared according to the reported
procedure [22]. The mixture of Scandium oxide and 3 equiv. of
bis(perfluorooctanesulfonyl)imide reacted in water under reflux
for 1 h. The resulting mixture was filtered through a membrane
filter. The Scandium bis(perfluorooctanesulfonyl)imide complex
4.3.7. 14-Phenyl-14H-dibenzo[a,j]xanthene (3g)
Colorless solid; mp 185–187 8C (185 8C, Ref. [11]). IR (KBr)
3070,1585, 1445, 1250, 1080, 965 cmÀ1. 1H NMR (CDCl3, 500 MHz)
: 6.45 (s, 1H), 6.96 (t, J = 7.2 Hz, 1H), 7.12 (t, J = 7.2 Hz, 2H), 7.37–
y
d
7.58 (m, 8H), 7.74–7.81 (m, 4H), 8.34 (d, 2H).
was obtained in 98% yield. ICP: Calcd. For Sc[N(SO2C8F17 2 3
1.51. Found: Sc, 1.47. Anal. Calcd. for Sc[N(SO2C8F17)2]3: C, 19.31.
Found: C, 19.23. 19F NMR:
À126.1, À121.2, À114.2, À81.4.
) ] : Sc,
4.3.8. 14-(4-Methoxyohenyl)-14H-dibenzo[a,j]xanthene (3h)
d
White solid; mp 203–206 8C (204 8C, Ref. [11]). IR (KBr) y 3038,
2910, 1615,1580, 1245, 820, 804 cmÀ1. 1H NMR (CDCl3, 500 MHz)
4.3. Typical procedure for the preparation of aryl(alkyl)-14H-
dibenzo[a,j]xanthenes
d: 3.72 (s, 3H), 6.48 (s, 1H), 6.75 (d, J = 7.5 Hz, 2H), 7.39 (t, J = 7.2 Hz,
2H), 7.53–7.89 (m, 10H), 8.41 (d, J = 8.5 Hz, 2H).
A mixture of aldehyde (1 mmol),
b
-naphthol (2 mmol) and
4.3.9. 14-(4-Tolyl)-14H-dibenzo[a,j]xanthene (3i)
Sc[N(SO2C8F17)2]3 (1 mol%) was heated at 110 8C in perfluorode-
calin for appropriate time indicated in Table 3. The reaction was
monitored by TLC. After completion of the reaction, the mixture
was cooled to room temperature and methylene dichloride
(10 mL) was added, and the mixture was stirred for another
5 min. The fluorous layer on the bottom was separated for the next
cycle. The upper methylene dichloride layer was washed with
brine, dried over anhydrous Na2SO4 and evaporated in vacuum.
The residue was recrystallized from ethanol to afford pure
products. Products were characterized by comparison of their
physical and spectral data with those of authentic samples.
White solid; mp 228–229 8C (229 8C, Ref. [11]). IR (KBr) y 3067,
3021, 2897, 1620, 1591, 1510 1458, 1432, 1399, 1246, 961, 810,
740, 608, 517, 488 cmÀ1. 1H NMR (CDCl3, 500 MHz)
: 2.12 (s, 3H),
d
6.45 (s, 1H), 6.93 (d, J = 7.5 Hz, 2H), 7.22–7.38 (m, 8H), 7.43–7.81
(m, 4H), 8.45 (d, J = 7.2 Hz, 2H).
4.3.10. 14-Ethyl-14H-dibenzo[a,j]xanthene (3j)
White solid; mp 150–152 8C (152 8C, Ref. [11]). IR (KBr)
2931, 1621, 1590, 1514, 1456, 1433, 1399, 1240, 1076, 960, 869,
809, 750, 705, 584, 503, 567 cmÀ1 1H NMR (CDCl3, 500 MHz)
d:
y 3065,
.
0.76 (t, J = 7.4 Hz, 3H), 2.14 (m, 2H), 5.57 (t, J = 4.3 Hz, 1H), 6.65 (d,
J = 7.5 Hz, 2H), 7.22–7.92 (m, 4H), 7.36–7.68 (m, 4H), 8.26 (d,
J = 8.4 Hz, 2H).
4.3.1. 14-(2-Chlorophenyl)-14H-dibenzo[a,j]xanthene (3a)
White solid; mp 216–218 8C (215 8C, Ref. [11]). IR (KBr)
2998, 1592, 1515, 1459, 1240, 961, 809, 745 cmÀ1. 1H NMR (CDCl3,
500 MHz) : 6.80 (s, 1H), 6.87–7.13 (m, 2H), 7.42–7.67 (m, 8H),
y 3058,
4.3.11. 14-Propyl-14H-dibenzo[a,j]xanthene (3k)
d
White solid; mp 151–153 8C (151–153 8C, Ref. [14b]). IR (KBr)
3061, 2953, 1591, 1434, 1399, 1243, 814, 747 cmÀ1 1H NMR
(CDCl3, 500 MHz) : 0.62 (t, J = 7.3 Hz, 3H), 1.01–1.08 (m, 2H), 2.03
y
7.79–7.86 (m, 4H), 8.73 (d, J = 8.5 Hz, 2H).
.
d
4.3.2. 14-(4-Chlorophenyl)-14H-dibenzo[a,j]xanthene (3b)
(m, 2H), 5.58 (t, J = 4.61 Hz, 1H), 7.39 (d, J = 9.2 Hz, 2H), 7.45–7.50
(m, 2H), 7.61–7.65 (m, 2H), 7.79 (d, J = 8.8 Hz, 2H), 7.89 (d,
J = 8.4 Hz, 2H), 8.26 (d, J = 8.8 Hz, 2H).
Yellow solid; mp 290–292 8C (289 8C, Ref. [11]). IR (KBr)
y 3066,
2922, 1622, 1590, 1514, 1456, 1397, 1245, 1237, 1209, 1140, 1065,
959, 812, 775, 746 cmÀ1. 1H NMR (CDCl3, 500 MHz)
: 6.46 (s, 1H),
d
6.97 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.5 Hz, 2H), 7.42–7.76 (m, 10 H),
8.39 (d, J = 8.7 Hz, 2H).
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