2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine as a new recyclable "iodoarene" for in situ generation of hypervalent iodine(III) reagent for α-tosyloxylation of enolizable ketones

Article abstract of DOI:10.1016/j.tetlet.2014.04.052

The synthesis of 2,4,6-tris[(4-iodo)phenoxy)]-1,3,5-triazine 6, as a new recyclable nonpolymeric analogue of iodobenzene is achieved using the reaction of 2,4,6-trichloro-1,3,5-triazine with 4-iodophenol in the presence of KOH. The application of 6 as a r

Full text of DOI:10.1016/j.tetlet.2014.04.052

Tetrahedron Letters 55 (2014) 3332–3335
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
2,4,6-Tris(4-iodophenoxy)-1,3,5-triazine as a new recyclable
‘‘iodoarene’’ for in situ generation of hypervalent iodine(III) reagent
for a-tosyloxylation of enolizable ketones
⇑
Prerana B. Thorat, Bhagyashree Y. Bhong, Amol V. Shelke, Nandkishor N. Karade
Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra 440 033, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of 2,4,6-tris[(4-iodo)phenoxy)]-1,3,5-triazine 6, as a new recyclable nonpolymeric analogue
Received 25 January 2014
Revised 11 April 2014
Accepted 15 April 2014
Available online 24 April 2014
of iodobenzene is achieved using the reaction of 2,4,6-trichloro-1,3,5-triazine with 4-iodophenol in the
presence of KOH. The application of 6 as a recyclable ‘iodoarene’ is demonstrated for
a-tosyloxylation
of enolizable ketones via in situ generation of hypervalent iodine(III) species using PTSA and MCPBA as
the terminal oxidant. The recyclability of the reagent 6 was possible owing to the facile recovery and
reuse from the reaction mixture due to its near insolubility in methanol.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Iodobenzene
m-Chloroperbenzoic acid
Enolizable ketone
p-Toluenesulfonic acid
a-Tosyloxyketones
Hypervalent iodine(III) and iodine(V) reagents have occupied a
seldom achieved. In view point of Green Chemistry, the formation
of iodoarene as by-product is one of the important shortcomings of
the process involving hypervalent iodine reagents as it diminishes
the overall atom-economy of the reaction.6 For example, the atom-
firm place in modern organic synthesis due to their low toxicity,
ready availability, mild conditions, excellent selectivity, and reac-
tivities with those of heavy metal (Pb, Tl, and Hg) oxidants.1 The
hypervalent iodine(III) reagent such as [hydroxy(tosyl-
oxy)iodo]benzene (HTIB) is the sole efficient reagent for inducing
economy of only 58.7% is achieved in the
a-tosyloxylation of
acetophenone using HTIB as the oxidant without quantitative
recovery of iodobenzene through column chromatographic purifi-
cation.7 This particular problem of atom-economy associated with
hypervalent iodine reagents has been resolved by using polymer
supported hypervalent iodine reagents which promotes the recov-
ery and recycling of iodoarenes due to simple filtration technique.8
Thus, the preparation of polymer supported HTIB and its
a
-tosyloxylation of enolisable ketones.2 The combination of p-tol-
uenesulphonic acid (PTSA) with other trivalent iodine reagents
such as (diacetoxyiodo)benzene3 and iodosylbenzene4 have been
also demonstrated for
resulting -tosyloxyketones are useful doubly electrophilic build-
ing blocks and are considered as environmentally benign alterna-
a-tosyloxylation of enolizable ketones. The
a
tives to the toxic and lachrymatory
generally not necessary to isolate the
be utilized in situ as strategic precursors for the one-pot synthesis
of a wide range of heterocycles such as thiazoles, selenazoles, oxaz-
oles, imidazoles, pyrazoles, and benzofurans.5
The HTIB and other hypervalent iodine reagents are commonly
used as stoichiometric oxidants in synthesis and after the reac-
tions, equimolar quantity of iodoarenes are produced as by-prod-
ucts. This demands extensive chromatographic purifications to
recover and reuse the relatively expensive iodoarenes from the
reaction mixture and a quantitative recovery of the iodoarene is
a
-haloketones. Since it is
application for a-tosyloxylation of enolizable ketones are known
a
-tosyloxyketone, they can
in the literature.9 However, these polymer supported hypervalent
iodine reagents require multi-step cumbersome preparation and
have poor solubility in various solvents. Furthermore, the repeated
use of polystyrene resin leads to the degradation of the polymeric
backbone due to benzylic oxidation of the polystyrene chain which
may affect the overall yield of the recyclability process. Another
progress for recovery and reuse of iodoarene has been achieved
by using room-temperature ionic liquid supported HTIB.10 In this
case, iodobenzene anchored to ionic liquid was recovered from
the reaction mixture up to 75% using acetonitrile as the eluent.
Apart from these strategies, Kita and coworkers have meticulously
identified recyclable non-polymeric trivalent iodine reagents based
on adamantane11 and tetraphenylmethane12 structures. The recy-
clability of these reagents is due to the near practical insolubility
⇑
Corresponding author. Tel.: +91 2462 266999; fax: +91 712 2534488.
E-mail address: nnkarade@gmail.com (N.N. Karade).
http://dx.doi.org/10.1016/j.tetlet.2014.04.052
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

P. B. Thorat et al. / Tetrahedron Letters 55 (2014) 3332–3335
3333
of ‘polyiodo derivatives’ in hexane or methanol. Based on this con-
cept, 4,40-bis[(hydroxy)(tosyloxy)iodo]biphenyl has been also
6 (0.33 equiv),
MCPBA (1.5 equiv),
PTSA (1.5 equiv)
O
O
R2
OTs
R2
demonstrated as the recyclable reagent for
a-tosyloxylation of
R1
R1
CH3CN, reflux
enolizable ketones due to insolubility of 4,40-diiodobiphenyl in
hexane.13
Scheme 1.
a
-Tosyloxylation of enolizable ketones.
The pioneering work of Ochiai et al. related to the in situ gener-
ation of hypervalent iodine(III) reagent using MCPBA as the termi-
nal oxidant has made this field more versatile.14 Accordingly, a
number of methods demonstrating in situ generation of hyperva-
lent iodine(III) using a catalytic15 as well as stoichiometric quantity
I
I
Cl
N
of iodoarenes for
a-tosyloxylation of enolizable ketones have
appeared in the literature. The various polymer16 as well as ionic
KOH
N
N
3
O
liquid17 supported ‘recyclable iodoarenes’ have been documented
acetone
48 h, rt
Cl
Cl
I
I
for the a-tosyloxylation of enolizable ketones via the in situ gener-
ation of hypervalent iodine(III) using MCPBA as the terminal oxi-
dant (Fig. 1).
N
N
OH
O
N
O
6
Recently, we reported the synthesis and applications of 2,4,6-
tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine as a new recyclable
nonpolymeric analogue of (dichloroiodo)benzene for chlorination
reaction and the oxidative synthesis of heterocycles.18 In this case,
the recyclability of 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-tri-
azine was possible owing to the facile recovery and reuse of the
co-produced 2,4,6-tris(4-iodophenoxy)-1,3,5-triazine 6 from the
reaction mixture due to its near insolubility in methanol. Herein,
Scheme 2. Synthesis of 2,4,6-tris[(4-dichloroiodo)phenoxy)]-1,3,5-triazine 6.
with various equivalents of triiodo derivative 6, PTSA, and MCPBA
as the terminal oxidant in CH3CN under reflux. It is observed from
Table 1 that the formation of
a-tosyloxyacetophenone 8a took
place using 0.1, 0.2, 0.5, and 1.0 equiv of 6 in combination with
PTSA (1.5 equiv) and MCPBA (1.5 equiv) as the terminal oxidant.
However, the maximum yield of 81% was achieved using 1.5 equiv
of 6 in shorter reaction time (4 h).21 It is important to note that the
formation of 8a did not take place in the absence of 6 which means
it acts as the catalyst. Under the present reaction conditions, the
formation of Baeyer–Villiger oxidation product was not observed.
The recyclability of the triiodo derivative 6 was achieved using
the solubility criteria which was previously reported for the polyi-
odo derivatives based on adamantane11 3, tetraphenylmethane12 4,
and 4,40-diiodobiphenyl13 5, structures. It was observed that 6 is
nearly insoluble (0.02 mg/mL) in methanol.22 Thus, after the
we wish to take advantage of this fact for a-tosyloxylation of enol-
izable ketones via in situ generation of hypervalent iodine(III) spe-
cies from 6 using MCPBA as the terminal oxidant. Accordingly, the
a-tosyloxylation of enolizable ketones was carried out using 6 as a
recyclable ‘iodoarene’, PTSA and MCPBA as the terminal oxidant
(Scheme 1).
Our initial studies started with the preparation of 2,4,6-tris(4-
iodophenoxy)-1,3,5-triazine 6.19 Thus, the reaction of 2,4,6-tri-
chloro-1,3,5-triazine (1 equiv) with a mixture of 4-iodophenol
(3 equiv) and KOH in acetone, under stirring condition, at room
temperature for 48 h, furnished 2,4,6-tris(4-iodophenoxy)-1,3,5-
triazine 6 in 93% yield (Scheme 2).20
completion of
a-tosyloxylation of ketones, the reaction solvent
(CH3CN) was evaporated under reduced pressure followed by
addition of methanol. The triiodide 6 was found to be insoluble
Next, the optimum reaction conditions for
were investigated by using the model reaction of acetophenone
a-tosyloxylation
Ionic liquid supported iodoarenes
I
Me
N
Me
Me
N
N
O
N
Br
N
I
N
Br
Br
O
I
1A
O
1B
1C
Polymer supported iodoarenes
O
O
O
10
6
O
I
O
I
I
PS
PS
PS
2A
2B
2C
Non-polymeric recyclable iodoarenes
I
I
Present work
I
I
O
I
I
I
N
N
I
I
O
N
6
O
I
I
I
(Near insolubility in methanol)
recyclable "iodoarene"
3
4
5
I
Figure 1. Recyclable ‘iodoarenes’ used for a-tosyloxylation of enolizable ketones.

3334
P. B. Thorat et al. / Tetrahedron Letters 55 (2014) 3332–3335
Table 1
shows that the triiodide 6 was still highly efficient after the third
cycle. After the recovery of triiodide 6, methanol from the filtrate
containing crude -tosyloxy ketone and 3-chlorobenzoic acid
was again removed under vacuum followed by treatment with
10% NaHCO3 solution. The resulting mixture was then extracted
with CHCl3 followed by drying on anhydrous sodium sulfate. The
combined organic extract was concentrated under vacuum to pro-
a
-Tosyloxylation of enolizable ketones using 6, PTSA and MCPBA in CH3CN under
reflux
a
6
O
O
mCPBA
p-TsOH.H2O
MeCN, reflux
OTs
7a
vide crude a-tosyloxy ketone which was subsequently purified by
column chromatography.
8a
Entry
6 (equiv)
m-CPBA
p-TSA
Time
Yielda (%)
With the optimum conditions in hand, we performed
a-tosyl-
oxylation reaction of wide range of ketones and the results are
summarized in Table 3. Various ketones such as alkyl aryl ketones
and cyclic ketones were treated with MCPBA and PTSA in the pres-
ence of recyclable triiodide 6 in acetonitrile under refluxing condi-
1
2
3
4
5
6
0.0333
0.0666
0.166
0.333
0.333
0
1.5
1.5
1.5
1.5
1.1
1.5
1.5
1.5
1.5
1.5
1.5
1.5
4 h
4 h
4 h
4 h
4 h
17
30
53
81
74
00
tions to provide the corresponding
good yields. The presence of electron donating and withdrawing
groups on acetophenones had little influence on the yield of
tosyloxylation products. Cyclic ketones such as cyclohexanone,
cyclopentanone, and -tetralone (Table 3, entries 8l–m) also
yielded respective -tosyloxylation products in good yields.
a-tosyloxyketones 8a–m in
3 days
a
Isolated yields.
a-
a
Table 2
Recycling of 6 in
a
a
-tosyloxylation of acetophenone
In conclusion, 2,4,6-tris[(4-iodo)phenoxy)]-1,3,5-triazine 6 is a
new recyclable ‘iodoarene’ which is prepared from relatively
inexpensive and readily available substrates such as 2,4,6-tri-
chloro-1,3,5-triazine and 4-iodophenol. Compared to the existing
analogues of recyclable iodoarene (Fig. 1), 2,4,6-tris[(4-iodo)phen-
oxy)]-1,3,5-triazine 6 is easy to prepare and there is an excellent
Run
Yield of 8aa (%)
Recovery of 6 (%)
1
2
3
81
74
68
93
84
72
a
Isolated yields.
recovery and reuse in the
a-tosyloxylation of enolizable ketones
due to its practical near insolubility in methanol.
Table 3
-Tosyloxylation of enolizable ketones using 6, PTSA and m-CPBA in CH3CN under
a
Acknowledgments
reflux
6 (0.33 equiv)
m-CPBA (1.5 equiv)
p-TsOH.H2O (1.5 equiv)
O
The authors are thankful to the Department of Science and
Technology, New Delhi, India (No. SR/S1/OC-72/2009) for the
financial support. The authors are also grateful to SAIF, Punjab Uni-
versity, Chandigarh, India, for recording the NMR spectra.
O
R2
O
R2
R1
R1
MeCN, reflux, 4-6 h
OTs
7a-m
8a-m
O
O
Supplementary data
Me
OTs
8b (79%)
OTs
OTs
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
04.052.
Me
8c (76%)
8a (81%)
O
O
O
MeO
References and notes
OTs
OTs
OTs
Br
MeO
Br
1. Reviews (a) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123; (b) Grushin,
V. V. Chem. Soc. Rev. 2000, 29, 315; (c) Zhdankin, V. V.; Stang, P. J. Chem. Rev.
2002, 102, 2523; (d) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656; (e)
Moriarty, R. M. J. Org. Chem. 2005, 70, 2893; (f) Zhdankin, V. V.; Stang, P. J. Chem.
Rev. 2008, 108, 5299; (g) Brown, M.; Farid, U.; Wirth, T. Synlett 2013, 424.
2. (a) Koser, G. F.; Wettach, R. H. J. Org. Chem. 1976, 41, 3609; (b) Koser, G. F.;
Wettach, R. H. J. Org. Chem. 1976, 42, 176; (c) Koser, G. F.; Wettach, R. H.; Smith,
C. S. J. Org. Chem. 1980, 45, 1542; (d) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.;
Rebrovic, L.; Wettach, R. H. J. Org. Chem. 1982, 47, 2487; (e) Moriarty, R. M.;
Vaid, R. K.; Koser, G. F. Synlett 1990, 365; (f) Varvoglis, A. Hypervalent Iodine in
Organic Synthesis; Academic Press: London, 1997; p 115. Chapter 7.
3. (a) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365; (b) Koser, G. F.
Aldrichimica Acta 2001, 34, 89; (c) Yusubov, M. S.; Wirth, T. Org. Lett. 2005, 7,
519; (d) Lee, J. C.; Choi, Ju. H. Synlett 2001, 234.
8d (81%)
8f (73%)
8e (84%)
O
O
O
Cl
OTs
OTs
OTs
8g (83%)
8h (77%)
8i (79%)
O
O
O
O
OTs
OTs
OTs
OTs
8j (78%)
8k (70%)
8l (63%)
8m (67%)
4. Ueno, M.; Nabana, T.; Togo, H. J. Org. Chem. 2003, 68, 6424.
5. (a) Koser, G. F.; Wettach, R. H. J. Org. Chem. 1977, 42, 1476; (b) Moriarty, R. M.;
Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.; Prakash, O. Tetrahedron Lett. 1990, 31, 201;
(c) Moriarty, R. M.; Vaid, B. K.; Duncan, M. P.; Levy, S. G.; Prakash, O.; Goyal, S.
Synthesis 1992, 845; (d) Prakash, O.; Goyal, S. Synthesis 1992, 629; (e) Prakash,
O.; Rani, N.; Goyal, S. J. Chem. Soc., Perkin Trans. 1 1992, 707; (f) Prakash, O.;
Saini, N.; Sharma, P. K. Synlett 1994, 221; (g) Prakash, O.; Saini, N.; Sharma, P. K.
Heterocycles 1994, 38, 409; (h) Uneno, M.; Togo, H. Synthesis 2004, 16, 2673; (i)
Calter, M. A.; Korotkov, A. Org. Lett. 2011, 13, 6328; Review (j) Merritt, E. A.;
Olofsson, B. Synthesis 2011, 4, 517.
6. Poliakoff, M.; Fitzpatrick, J. M.; Farren, T. R.; Anastas, P. T. Science 2002, 297,
807. and references therein.
7. (a) Lenoir, D. Angew. Chem., Int. Ed. 2006, 45, 3206; (b) Lenoir, D. Angew. Chem.,
Int. Ed. 2006, 118, 3280.
Reaction conditions: Ketone (1.0 equiv), 6 (1.5 equiv), p-TSA (1.5 equiv), and m-
CPBA (1.5 equiv) in CH3CN (10 mL) under reflux.
in methanol. The resulting heterogeneous solution was then fil-
tered, and the solid on the filter was washed several times with
small amounts of methanol to recover 6 which was subsequently
reused for
a-tosyloxylation reaction. The recycling results for the
a-tosyloxylation of acetophenone are listed in Table 2 which

P. B. Thorat et al. / Tetrahedron Letters 55 (2014) 3332–3335
3335
8. Polymer supported hypervalent iodine reagents. Review: (a) Sakuratani, K.;
Togo, H. Synlett 2002, 1966; (b) Hossain, Md. D.; Kitamura, T. Synthesis 2006,
1253; (c) Teduka, T.; Togo, H. Synlett 2005, 923; (d) Lei, Z.; Denecker, C.;
Jegasothy, S.; Sherrington, D. C.; Slater, N. K. H.; Sutherland, A. J. Tetrahedron Lett.
2003, 44, 1635; (e) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Tetrahedron Lett. 2003, 44,
9251; (f) Ficht, S.; Mülbaier, M.; Giannis, A. Tetrahedron 2001, 57, 4863; (g)
Mülbaier, M.; Giannis, A. Angew. Chem., Int. Ed. 2001, 40, 4393; (h) Sorg, G.;
Mengel, A.; Jung, G.; Rademann, J. Angew. Chem., Int. Ed. 2001, 40, 4395.
9. Polymer supported HTIB: (a) Abe, S.; Sakuratani, K.; Togo, H. Synlett 2001, 22;
(b) Abe, S.; Sakuratani, K.; Togo, H. J. Org. Chem. 2001, 66, 6174; (c) Sakuratani,
K.; Togo, H. ARKIVOC 2003, 11; (d) Ueno, M.; Togo, H. Synthesis 2004, 2673.
10. Ionic liquid supported HTIB: Handy, S. C.; Okello, M. J. Org. Chem. 2001, 66,
6174.
20. Preparation of 2,4,6-tris(4-iodophenoxy)-1,3,5-triazine (6): Potassium hydroxide
(20 mmol, 1.12 g) was dissolved in acetone (150 mL) and stirred for 45 min. 4-
Iodophenol (20 mmol, 4.4 g) was then added to this solution and again stirred
for 30 min. The resulting mixture was cooled to 0 °C and cyanuric chloride
(5 mmol, 0.92 g) was added and again stirred for 1 h. The reaction mixture was
allowed to stir for 48 h at room temperature, poured into crushed ice, the
resulting white precipitate was suction filtered, and then washed with
methanol to get 6 in 93% yield. Nature: White solid, yield = 94%, Mp: 236–
238 °C; 1H NMR (CDCl3, 400 MHz): d 6.88 (d, 2H, J = 8.60 Hz, ArH), 7.66 (d, 2H,
J = 8.64 Hz, ArH); 13C NMR (CDCl3, 100 MHz): d 90.54, 123.56, 138.65, 151.26,
173.40; IR (cmꢀ1): 1589, 1562, 1480, 1378, 1358, 1204, 1172, 1055, 1008, 820,
803, 704; MS (ESI) m/z (M+H)+ calculated for formula C21H12I3N3O3:734.8,
found: 735.75.
11. (a) Dohi, T.; Fukushima, K.; Kamitanaka, T.; Morimoto, K.; Takenagab, N.; Kita,
Y. Green Chem. 2012, 14, 1493; (b) Tohma, H.; Maruyama, A.; Maeda, A.;
Maegawa, T.; Dohi, T.; Shiro, M.; Morita, T.; Kita, Y. Angew. Chem., Int. Ed. 2004,
43, 3595.
12. Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Shiro, M.;
Kita, Y. Chem. Commun. 2005, 2205.
13. (a) Moroda, A.; Togo, H. Tetrahedron 2006, 62, 12408; (b) Yusubov, M. S.;
Drygunova, L. A.; Zhadankin, V. V. Synthesis 2004, 2289.
14. (a) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem.
Soc. 2005, 127, 12244; (b) Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed.
2006, 45, 4402; (c) Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem. 2008, 5229; (d)
Nakashima, K.; Tada, N.; Itoh, A. Chem. Commun. 2011, 1875.
21. General procedure for a-tosyloxylation of enolizable ketone (8a–m): A mixture of
appropriate enolizable ketone (2 mmol), 2, 4, 6-tris(4-iodophenoxy)-1,3,5-
triazine (0.33 mmol), PTSA (2.3 mmol), and MCPBA (2.3 mmol) in CH3CN
(10 mL) was refluxed for 4–6 h. The progress of the reaction was monitored by
TLC. When the substrate was consumed, CH3CN was evaporated under reduced
pressure. Methanol was added to the reaction mass, and the white precipitate
was isolated by filtration. A small amount of methanol wash was given several
times and air dried to give 2, 4, 6-tris(4-iodophenoxy)-1,3,5-triazine in 84–93%
yield. The filtrate (MeOH) of the above reaction mixture was concentrated in
vacuo to afford the crude product which was treated with 10% NaHCO3
followed by solvent extraction using CHCl3. The combined organic layers were
dried over anhydrous sodium sulfate followed by concentration in vacuo to
15. Yamamoto, Y.; Togo, H. Synlett 2006, 798.
afford the crude a-tosyloxy ketone 8a–m which was subsequently purified by
16. Akiike, J.; Yamamoto, Y.; Togo, H. Synlett 2007, 2168.
17. (a) Yamamoto, Y.; Kawano, Y.; Toy, P. H.; Togo, H. Tetrahedron 2007, 63, 4680;
(b) Suzuki, Y.; Togo, H. Synthesis 2010, 2355.
18. Thorat, P. B.; Bhong, B. Y.; Karade, N. N. Synlett 2013, 2061.
19. (a) Saha, B. K.; Jetti, R. K. R.; Reddy, S.; Aitipamula, S.; Nangia, A. Cryst. Growth
Des. 2005, 5, 887; (b) Saha, B. K.; Aitipamula, S.; Banerjee, R.; Nangia, A.; Jetti, R.
K. R.; Boese, R.; Lam, C. K.; Mak, T. C. W. Mol. Cryst. Liq. Cryst. 2005, 440, 295; (c)
Desiraju, G. R. Acc. Chem. Res. 2002, 35, 565.
column chromatography on silica gel using petroleum ether/EtOAc 9:1 as
eluent.
22. The measured solubilities of the triiodide 6 in several (mixed) solvents at 25 °C are
as follows: 0.02 mg mLꢀ1 (methanol); 0.02 mg mLꢀ1 (isopropanol);
0.2 mg mLꢀ1 (acetonitrile); 4.1 mg mLꢀ1 (ethyl acetate); 4.3 mg mLꢀ1
(acetone); 0.04 mg mLꢀ1 (methanol–ethyl acetate = 10:1); 0.06 mg mLꢀ1
(methanol–ethyl acetate = 5:1); 0.6 mg mLꢀ1 (methanol–ethyl acetate = 1:1).