Mechanochemical synthesis of 2,2-difluoro-4, 6-bis(β-styryl)-1,3,2-dioxaborines and their use in cyanide ion sensing

Article abstract of DOI:10.1515/hc-2015-0096

The conversion of arylaldehydes to 1,7-diaryl-5-hydroxyhepta-1,4,6-trien-3-ones (curcuminoids) and the mechanochemical cyclization of these products to 2,2-difluoro-4,6-bis(β-styryl)-1,3,2-dioxaborines using BF₃-Et₂O are described. Investigation of the cyanide ion sensing ability of the 2,2-difluoro-4,6-bis(β-styryl)-1,3,2-dioxaborines, in relation to the substituent groups on the aryl ring, showed that a hydroxy susbstituent is required, preferably para to the intervening carbon bridge.

Full text of DOI:10.1515/hc-2015-0096

Heterocycl. Commun. 2015; 21(6): 381–385
Daisy R. Sherin, Sherin G. Thomas and Kallikat N. Rajasekharan*
Mechanochemical synthesis of 2,2-difluoro-4,
6-bis(β-styryl)-1,3,2-dioxaborines and their use
in cyanide ion sensing
DOI 10.1515/hc-2015-0096
Received May 15, 2015; accepted July 31, 2015; previously published
online November 9, 2015
Reported methods for the synthesis of curcuminoid-
BF2 complexes include the reaction of the natural cur-
cuminoids, or synthetic ones obtained from arylaldehyde,
boric acid and 1,3-pentanedione, with boron trifluoride
etherate. These complexes can also be prepared by con-
densation of arylaldehydes with 2,2-difluoro-1,3-diox-
aborylpentadione. Both routes however, afford these
complexes in generally low yields. For example, Ran
and co-workers [7, 8] have reported yields in the range
of 14–20% for 2,2-difluoro-1,3,2-dioxaborines obtained
by the bis-condensation of arylaldehydes with 2,2-dif-
luoro-1,3-dioxaborylpentadione at 60°C overnight. More
recently, Bai et al. [12] have prepared BF2 complexes,
Abstract: The conversion of arylaldehydes to 1,7-diaryl-
5-hydroxyhepta-1,4,6-trien-3-ones (curcuminoids) and
the mechanochemical cyclization of these products to
2,2-difluoro-4,6-bis(β-styryl)-1,3,2-dioxaborinesꢀusing
BF3-Et2O are described. Investigation of the cyanide ion
sensing ability of the 2,2-difluoro-4,6-bis(β-styryl)-1,3,2-
dioxaborines, in relation to the substituent groups on the
aryl ring, showed that a hydroxy susbstituent is required,
preferably para to the intervening carbon bridge.
Keywords: cyanide; 2,2-difluoro-4,6-bis(β-styryl)-1,3,2- including π-extended systems, by reacting arylaldehydes,
dioxaborines; mechanochemical.
hetarylaldehydes and cinnamaldehydes with 2,2-difluoro-
1,3-dioxaborylpentadione in toluene at room tempera-
ture for 2 h in 15–45% yield. Feloaut and co-workers [13]
obtained two curcuminoid-BF2 complexes in 61 and 74%
yield by reacting the curcuminoids and boron trifluoride
etherate in dichloromethane at reflux for 24 h. In a similar
way, a long reaction time has been reported by Sui and
co-workers [10] in seemingly the first report of the synthe-
sis of a curcumin-BF2 complex. With our interest in the
synthesis and bioactivity of curcuminoids [14–16], we now
report a mild two-stage synthetic route to access curcumin
templated 1,3,2-dioxaborines.
Introduction
The design and development of 1,3,2-dioxaborine based
fluorophores is a growing area of research with applica-
tions in sensing and biomedical imaging [1–4]. 1,3-Dik-
etones form stable 2,2-difluoro-1,3,2-dioxaborines, also
termed as difluoroboron complexes, that exhibit interest-
ing photophysical properties. Curcuminoids are 1,3-dik-
etones, existing preferentially as enol tautomers [5], and
belong to the diarylheptanoid class of natural products.
These
(1E,4Z,6E)-1,7-diaryl-5-hydroxyhepta-1,4,6-trien-
3-ones have served as useful precursors for the synthesis Results and discussion
of 2,2-difluoro-1,3,2-dioxaborine scaffold based cyanide
sensing fluoroprobe [6], NIR probes for amyloid β-deposits The (1E,4Z,6E)-1,7-diaryl-5-hydroxyhepta-1,4,6-trien-
[7–9], inhibitors for HIV proteases [10] and NIR lumino- 3-ones 1a–i were prepared by microwave irradiation
phores [11]. Recently, BF2 complexes of π-extended cur- of a mixture of arylaldehyde, acetylacetone and boric
cuminoids have been described that show solvatochromic acid in a mixed solvent consisting of a small amount
and solvatofluorochromic properties [12].
of N,N-dimethylformamide (DMF), glacial acetic acid
and 1,2,3,4-tetrahydroquinoline (THQ) as catalyst for
20 min. This method is a great improvement over the
method reported previously which required heating at
85°C for 4 h [14]. Among different solvents tried, includ-
ing DMF, dimethyl sulfoxide, N-methylpyrrolidine and
N,N-dimethylacetamide, DMF was the best and with
*Corresponding author: Kallikat N. Rajasekharan, Department of
Chemistry, University of Kerala, Kariavattom, Thiruvananthapuram
695581, Kerala, India, e-mail: rajkn_1951@yahoo.com
Daisy R. Sherin and Sherin G. Thomas: Department of Chemistry,
University of Kerala, Kariavattom, Thiruvananthapuram 695581,
Kerala, India
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382ꢀ ꢀD.R. Sherin et al.: 1,3,2-Dioxaborines
Scheme 1ꢀSynthetic route for curcuminoid 1,3,2-dioxaborines.
various amines tried as catalyst, THQ was found to work
Chaicham and co-workers have reported the cyanide
best, followed by diethanolamine, on the basis of yield ion sensing ability of curcumin-BF2 complex 2a. These
and purity of the crude product. This use of THQ-acetic workers have attributed the selective detection of cyanide
acid in curcumin synthesis has been adopted by others to the deprotonation of the two phenolic groups, fol-
[9, 17]. We also observed that boric acid could also serve lowed by an intramolecular charge transfer process, as
as the boron source and the addition of a tri-n-butyl well as to the basicity of cyanide ion [6]. We examined the
borate did not improve the yield [9, 17]. The reaction cyanide anion sensing ability of 2a–i and concluded that
mixture was worked up by a dropwise addition to 20% a hydroxy group on the aryl rings, para to the intervening
aqueous acetic acid under very rapid stirring to afford seven carbon bridge, is a structural feature that imparts a
a crude product, which was further purified by planar good cyanide ion sensing ability.
preparative chromatography (PTLC). The curcuminoids
Thus, the 2,2-difluoro-1,3,2-dioxaborines 2a and 2b,
1a–i, obtained in yields of 61–79%, were then efficiently both having a 4-hydroxyaryl moiety, show an excellent
converted to the corresponding BF2 complexes in yields ability to sense cyanide ion under the conditions of this
of 87–93% by neat grinding of these compounds with work (Figures 1 and 2). Between compounds 2a and 2b,
BF3-etherate for a few minutes (Scheme 1 and Table 1). the former compound exhibits a stronger response. Since
The resultant complexes 2a–i were characterized by the response of 2a to cyanide ion is stronger than that
1
FTIR, H NMR, 13C NMR and HRMS. The products 2b–d, of 2b, factors other than pKa of the phenolic hydroxyl
2h and 2i have not been described previously. The syn- group may also play a role in the sensing mechanism,
thesized BF2 complexes are excellent D-A-D molecules since the phenolic group in 2b would be expected
having electron donor (D) moieties at both ends of the to be deprotonated easier. The compound 2c, with a
conjugated system and an electron acceptor (A) moiety
in the middle of the molecule.
2
2a
2b
2c
Table 1ꢀYields of 2,2-difluoro-4,6-bis[β-(styryl)]-1,3,2-dioxaborines.
1.6
2d
2e
2f
2g
2h
2i
2,2-Difluoro-4,6-bis[β-(styryl)]-ꢁ
1,3,2-dioxaborine
Yieldꢁ
(%)
Reported
yield (%)
1.2
0.8
0.4
0
2a
2b
2c
2d
2e
2f
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
ꢂ
93ꢂ
91ꢂ
87ꢂ
92ꢂ
89ꢂ
90ꢂ
89ꢂ
90ꢂ
88ꢂ
32 [12]
–
–
–
45 [12]
400
450
500
550
600
650
700
750
800
73 [6]
Wavelength (nm)
2g
2h
2i
15 [7], 24 [12]
–
–
Figure 1ꢀAbsorption spectra of 5ꢂ×ꢂ10-6 m solutions of curcuminoid
2,2-difluoro-1,3,2-dioxaborines 2a–i in MeCN/H2O (4:1).
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D.R. Sherin et al.: 1,3,2-Dioxaborinesꢃ
ꢃ383
2
1.6
1.2
0.8
0.4
0
0.4
0.3
0.2
0.1
0
pH 1
pH 2
pH 3
pH 4
pH 5
pH 6
pH 7
pH 8
pH 9
pH 10
pH 11
pH 12
pH 13
pH 14
2a+CN
2b+CN
2c+CN
2d+CN
2e+CN
2f+CN
2g+CN
2h+CN
2i+CN
400 450 500 550 600 650 700 750 800
400
450
500
550
600
650
700
750
Wavelength (nm)
Wavelength (nm)
Figure 2ꢀAbsorption spectra of 5ꢂ×ꢂ10-6 m solutions of curcuminoid
2,2-difluoro-1,3,2-dioxaborines 2a–i in presence of 100 molar
excess of cyanide ion in MeCN/H2O (4:1).
Figure 4ꢀAbsorption spectra of 2,2-difluoro-4,6-bis[β-(4-hydroxy-3-
methoxystyryl)]-1,3,2-dioxaborine (2a) in MeCN/H2O (4:1) solutions
of pH range 1–14.
3-hydroxyaryl group, and 2d with a 2-hydroxyaryl group
respond very poorly, whereas those 2,2-difluoro-1,3,2-
dioxaborines with no hydroxyaryl group, such as 2e–i,
do not respond markedly. The sensing of cyanide anion
by 2,2-difluoro-1,3,2-dioxaborines 2a and 2b is insen-
sitive to the presence of other anions including chlo-
ride, fluoride, phosphate, nitrite, nitrate and sulfate
(Figure 3).
We also examined the response of the curcumin-BF2
complex 2a to pH using MeCN/H2O solution in the pH
range 1–14 (Figure 4). This study revealed that a change
in pH is paralleled by a change in color. This observa-
tion indicates that the basis for cyanide ion sensing by
curcumin-BF2 complex 2a is probably due to an acid-base
reaction between cyanide ion and 2a, as suggested by
Chiacham and co-workers [6]. It appears that in order to
analyze the presence of cyanide ion using 2a as a sensor,
the pH of the analyte aqueous solution should preferably
be in the range of 7–9.
Conclusions
In summary, we have synthesized several curcuminoids
and converted these compounds to 2,2-difluoro-4,6-bis[β-
(styryl)]-1,3,2-dioxaborines with a D-A-D motif under mild
conditions in a very good overall yield. The structural
feature required for conferring a cyanide ion sensing
ability by these compounds is a 4-HOC6H4 functionality.
Experimental
Reagents and solvents used were of analytical grade. Analytical thin
layer chromatography (TLC) and preparative thin layer chromato-
graphy (PTLC) were performed on glass plates (20 mmꢁ×ꢁ75 mm
and 20 cmꢁ×ꢁ20 cm, respectively) coated with TLC grade silica gel-G
(E. Merck, India). Preparative chromatography was conducted using
dry columns as reported earlier by us [14]. The spots or bands were
visualized directly or under UV light. The elemental analyses were
carried out on a Vario EL elemental analyzer. The H and 13C NMR
1
spectra were recorded on Bruker Topspin and Bruker AV spectro-
meters at room temperature. HRMS were recorded on JEOL JMS 600H
mass spectrometer. The UV-Vis absorption spectra of the complexes
in the presence and absence of ions were recorded on a HALO DB-20
UV-Vis spectrophotometer.
2
2a
1.6
2a+Cyanide
2a+Chloride
1.2
0.8
0.4
0
2a+Fluoride
2a+Phosphate
2a+Nitrite
General procedure for the synthesis of curcuminoids
(1a–i)
2a+Nitrate
2a+Sulphate
To a mixture of arylaldehyde (2 mmol), acetylacetone (1 mmol) and
boric acid (0.2 g), a small amount of DMF (1 mL) was added to obtain
a pasty mass. The mixture was then subjected to MW irradiation at
320 W in a multimode microwave oven for 5 min. To the clear mixture
thus obtained, glacial acetic acid (60 μL) and 1,2,3,4-tetrahydroqui-
noline (20 μL) in DMF (0.5 mL) were added and MW irradiation was
continued for 15 min. During irradiation, the mixture was cooled for
400 450 500 550 600 650 700 750 800
Wavelength (nm)
Figure 3ꢀAbsorption spectra of 5ꢂ×ꢂ10-6 m solutions of 2,2-difluoro-
4,6-bis[β-(4-hydroxy-3-methoxystyryl)]-1,3,2-dioxaborine (2a) in
presence of 100 molar excess of various ions in MeCN/H2O (4:1).
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384ꢀ ꢀD.R. Sherin et al.: 1,3,2-Dioxaborines
short periods at regular intervals. Afer the reaction was completed,
2,2-Difluoro-4,6-bis[β-(3-hydroxy-4-methoxystyryl)]-1,3,2-
the deeply colored mixture was diluted with DMF (1 mL) and added dioxaborine (2c)ꢂThis compound was obtained as red solid in 87%
slowly to 20% aqueous acetic acid (10 mL) under rapid stirring. The yield; mp 162°C; 1H NMR (400 MHz, CDCl3): δ 3.95 (s, 6H, OMe), 5.98
precipitate obtained afer stirring for 2 h was filtered and dried. The (s, 1H, 5-H), 6.53 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.2 Hz), 6.95–7.21 (m, 6H, ArH),
purity of the product was checked by TLC and it was further purified 7.96 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.2 Hz), 9.46 (s, 2H, ArOH); 13C NMR (125 MHz,
by preparative TLC (CHCl3/MeOH, 95:5). The identity of the curcumi- DMSO-d6): δ 179.1, 150.5, 148.7, 147.7, 146.9, 140.5, 126.3, 125.8, 125.2,
noids 1a–g were established by comparison (TLC, IR) with samples 123.1, 121.1, 117.6, 115.7, 112.3, 111.3, 100.8, 55.6, 55.6. ESI-HRMS. Calcd
+
prepared earlier in our laboratories [14].
for C21H19BF2O6 (M+Na) : m/z 439.1140. Found: m/z 439.1137.
(1E,4Z,6E)-5-Hydroxy-1,7-bis(indol-3-yl)ꢀhepta-1,4,6-trien-3-one 2,2-Difluoro-4,6-bis[β-(2-hydroxystyryl)]-1,3,2-dioxaborine
(1h)ꢂThis compound was obtained as red solid in 65% yield; mp (2d)ꢂThis compound was obtained as red solid in 92% yield; mp
210°C; H NMR (500 MHz, DMSO-d6): δ 6.15 (s, 1H, 4-H), 6.71 (d, 2H, 158°C; 1H NMR (400 MHz, DMSO-d6): 5.81 (s, 1H, 5-H), 6.80 (d, 2H, 2,6-
1
2,6-H, Jꢃꢁ=ꢁꢃ16 Hz), 7.19–7.25 (m, 4H, ArH), 7.48 (d, 2H, ArH, Jꢃꢁ=ꢁꢃ7.5 Hz), H, Jꢃꢁ=ꢁꢃ16.0 Hz), 6.88–7.41 (m, 8H, ArH), 7.49 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ16.0 Hz),
7.85 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ16 Hz), 7.96 (s, 2H, ArH), 7.98 (d, 2H, ArH, 9.80 (s, 2H, ArOH); 13C NMR (100 MHz, CDCl3): δ 186.8, 180.2, 155.1,
Jꢃꢁ=ꢁꢃ7.5 Hz), 11.81 (s, 2H, Ar-NH); 13C NMR (125 MHz, DMSO-d6): δ 183.2, 150.1, 131.4, 130.4, 129.2, 126.6, 125.5, 114.0, 98.1. ESI-HRMS. Calcd for
+
C19H15BF2O4 (M+H) : m/z 357.1110. Found: m/z 357.2404.
137.5, 134.3, 131.8, 124.9, 122.6, 120.9, 120.0, 118.2, 112.7, 112.4, 100.0.
+
ESI-HRMS. Calcd for C23H18N2O2 (M+Na) : m/z 377.1266. Found: m/z
2,2-Difluoro-4,6-bis[β-(4-methoxystyryl)]-1,3,2-dioxaborine
(2e)ꢂThis compound was obtained as red solid in 89% yield; mp
150°C, Lit. [13] mp 247–249°C; 1H NMR (500 MHz, DMSO-d6): δ 3.85 (s,
6H, OMe), 6.57 (s, 1H, 5-H), 6.73 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.4 Hz), 7.20 (d, 4H,
ArH, Jꢃꢁ=ꢁꢃ8.2 Hz), 7.88 (d, 4H, ArH, Jꢃꢁ=ꢁꢃ8.2 Hz), 8.14 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.4
Hz); 13C NMR (100 MHz, DMSO-d6): δ 179.6, 161.8, 147.3, 130.6, 130.5,
128.8, 128.6, 128.4, 128.3, 127.9, 127.1, 114.4, 101.7, 55.7. ESI-HRMS. Calcd
377.1266. Anal. Calcd for C23H18N2O2: C, 77.95; H, 5.12; N, 7.90. Found:
C, 77.89; H, 5.13; N, 7.89.
(1E,4Z,6E)-5-Hydroxy-1,7-bis(thiophen-3-yl)hepta-1,4,6-trien-
3-one (1i)ꢂThis compound was obtained as yellowish brown solid
1
in 69% yield; mp 189°C; H NMR (500 MHz, DMSO-d6): δ 6.19 (s, 1H,
4-H), 6.58 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.5 Hz), 7.18 (s, 2H, ArH), 7.54 (d, 2H, ArH,
Jꢃꢁ=ꢁꢃ4.5 Hz), 7.75 (d, 2H, ArH, Jꢃꢁ=ꢁꢃ4.5 Hz), 7.82 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.5 Hz);
13C NMR (125 MHz, DMSO-d6): δ 182.5, 139.8, 133.2, 132.0, 130.0, 128.8,
+
for C21H19BF2O4 (M+H) : m/z 385.1423. Found: m/z 385.1489.
+
2,2-Difluoro-4,6-bis[β-(3,4-dimethoxystyryl)]-1,3,2-dioxaborine
(2f)ꢂThis compound was obtained as red solid in 90% yield; mp
152°C; 1H NMR (500 MHz, DMSO-d6): δ 3.34 (s, 12H, OMe), 6.57 (s, 1H,
5-H), 6.73 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.9 Hz), 7.10 (s, 2H, ArH), 7.19 (d, 2H, ArH,
Jꢃꢁ=ꢁꢃ8.35 Hz), 7.71 (d, 2H, ArH, Jꢃꢁ=ꢁꢃ8.6 Hz), 8.14 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.9 Hz);
13C NMR (100 MHz, DMSO-d6): δ 186.3, 181.1, 150.0, 147.8, 146.2, 130.5,
128.8, 119.1, 114.1, 112.0, 99.1, 56.3. ESI-HRMS. Calcd for C23H23BF2O6
122.7, 101.5; ESI-HRMS. Calcd for C15H12S2O2 (M+Na) : m/z 311.0176.
Found: m/z 311.0179. Anal. Calcd for C15H12S2O2: C, 62.47; H, 4.19.
Found: C, 62.35; H, 4.02.
General procedure for synthesis of curcuminoid
2,2-difluoro-1,3,2-dioxaborines 2a–i
+
(M+H) : m/z 445.1634. Found: m/z 445.1807.
BF3·OEt2 (0.12 mL, 1 mmol) was added to the curcuminoid 1a–h
(1 mmol) in an agate mortar and the mixture was ground with an
agate pestle for a few seconds whereupon the mixture changed its
color rapidly. The whole pasty mass soon solidified and further
turned into a solid that had the appearance of a crystalline mate-
rial. The crude product was purified by preparative TLC (CHCl3/
MeOH, 95:5).
2,2-Difluoro-4,6-bis[β-(4-N,N-dimethylaminostyryl)]-1,3,2-
dioxaborine (2g)ꢂThis compound was obtained as dark blue
1
solid in 89% yield; mp 144°C; H NMR (400 MHz, DMSO-d6): δ 3.09
(s, 12H, NMe2), 6.26 (s, 1H, 5-H), 6.78 (d, 4H, ArH, Jꢃꢁ=ꢁꢃ7.5 Hz), 7.66 (d,
4H, ArH, Jꢃꢁ=ꢁꢃ8.4 Hz), 7.80 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.6 Hz), 7.95 (d, 2H, 1,7-H,
Jꢃꢁ=ꢁꢃ15.6 Hz); 13C NMR (100 MHz, DMSO-d6): δ 179.6, 153.3, 145.7, 131.2,
129.2, 124.0, 116.0, 112.2, 99.2, 44.3. ESI-HRMS. Calcd for C23H25BF2N2O2
+
(M+Na) : m/z 433.1875. Found: m/z 433.1870.
2,2-Difluoro-4,6-bis[β-(4-hydroxy-3-methoxystyryl)]-1,3,2-
dioxaborine (2a)ꢂThis compound was obtained as red solid in 93%
yield; mp 147°C; 1H NMR (400 MHz, CDCl3): δ 3.96 (s, 6H, OMe), 6.01
(s, 1H, 5-H), 6.54 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.2 Hz), 6.95–7.21 (m, 6H, ArH)
7.95 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.2 Hz), 9.60 (s, 2H, ArOH); 13C NMR (125 MHz,
DMSO-d6): δ 183.2, 178.7, 151.3, 149.3, 148.1, 148.0, 146.9, 140.7, 126.3,
126.0, 125.2, 123.1, 121.1, 117.8, 115.9, 115.7, 112.4, 111.3, 101.1, 100.8, 55.7,
2,2-Difluoro-4,6-bis[β-(indol-3-yl)ethenyl]-1,3,2-dioxaborine
(2h)ꢂThis compound was obtained as red solid in 90% yield; mp
1
161°C; H NMR (500 MHz, DMSO-d6): δ 6.30 (s, 1H, 5-H), 6.41 (d, 2H,
ArH, Jꢃꢁ=ꢁꢃ8.6 Hz), 6.75 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ15.7 Hz), 6.80 (d, 2H, ArH,
Jꢃꢁ=ꢁꢃ8.6 Hz), 6.86–6.92 (dd, 4H, ArH), 7.68 (s, 2H, ArH), 7.84 (d, 2H,
1,7-H, Jꢃꢁ=ꢁꢃ15.7 Hz), 8.27 (s, 2H, Ar-NH); 13C NMR (125 MHz, DMSO-d6):
δ 178.8, 151.3, 137.3, 136.1, 132.1, 128.3, 126.9, 126.0, 125.3, 123.4, 121.1,
+
55.7. ESI-HRMS. Calcd for C21H19BF2O6 (M+Na) : m/z 439.1140. Found:
+
m/z 439.1139.
112.4, 111.7, 101.1, 100.8. ESI-HRMS. Calcd for C23H17BF2N2O2 (M+Na) :
m/z 425.1249. Found: m/z 425.1245.
2,2-Difluoro-4,6-bis[β-(4-hydroxystyryl)]-1,3,2-dioxaborine
(2b)ꢂThis compound was obtained as red solid in 91% yield; mp 2,2-Difluoro-4,6-bis[β-(thiophen-3-yl)ethenyl]-1,3,2-dioxaborine
1
169°C; H NMR (400 MHz, CDCl3): δ 6.05 (s, 1H, 5-H), 6.54 (d, 2H, (2i)ꢂThis compound was obtained as red solid in 88% yield; mp
1
2,6-H, Jꢃꢁ=ꢁꢃ15.2 Hz), 6.96–7.20 (m, 8H, ArH) 7.96 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ15.2 171°C; H NMR (500 MHz, DMSO-d6): δ 6.76 (d, 2H, ArH, Jꢃꢁ=ꢁꢃ7.5 Hz),
Hz), 9.03 (s, 2H, ArOH); 13C NMR (100 MHz, DMSO-d6): δ 186.0, 179.2, 6.92 (s, 1H, 5-H), 6.99 (d, 2H, ArH, Jꢃꢁ=ꢁꢃ7.5 Hz), 7.18 (d, 2H, 2,6-H, Jꢃꢁ=ꢁꢃ13.1
155.8, 150.0, 130.7, 129.3, 128.2, 126.6, 114.2, 98.7. ESI-HRMS. Calcd for Hz), 7.34 (s, 2H, ArH), 7.35 (d, 2H, 1,7-H, Jꢃꢁ=ꢁꢃ13.1 Hz); 13C NMR (125 MHz,
+
C19H15BF2O4 (M+H) : m/z 357.1110. Found: m/z 357.2402.
DMSO-d6): δ 178.8, 140.0, 139.5, 139.3, 135.3, 133.6, 129.8, 129.4, 128.7,
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ꢁꢀꢀꢀ
D.R. Sherin et al.: 1,3,2-Dioxaborinesꢃ
ꢃ385
+
[5] Balasubramanian, K. Molecular orbital basis for yellow curry
spice curcumin’s prevention of Alzheimer’s disease. J. Agric.
Food Chem. 2006, 54, 3512–3520.
119.4, 101.9. ESI-HRMS. Calcd for C15H11BF2S2O2 (M+Na) : m/z 359.0159.
Found: 359.01554.
[6] Chaicham, A.; Kulchat, S.; Tumcharern, G.; Tuntulani, T.;
Tomapatanaget, B. Synthesis, photophysical properties and
cyanide detection in aqueous solution of BF2-curcumin dyes.
Tetrahedron. 2010, 66, 6217–6223.
[7] Ran, C.; Xu, X.; Raymond, S. B.; Ferrara, B. J.; Neal, K.;
Bacskai, B. J.; Medarova, Z.; Moore, A. Design, synthesis and
testing of difluoroboron-derivatized curcumins as near-IR
probes for in vivo detection of amyloid-β deposits. J. Am.
Chem. Soc. 2009, 131, 15257–15261.
[8] Zhang, X.; Tian, Y.; Li, Z.; Tian, X.; Sun, H.; Liu, H.; Moore, A.;
Ran, C. Design and synthesis of curcumin analogues for in vivo
fluorescence imaging and inhibiting copper-induced cross-
linking of amyloid beta species in Alzheimer’s disease. J. Am.
Chem. Soc. 2013, 135, 16397–16409.
UV-Vis spectrophotometric study of the interaction
of curcuminoid 2,2-difluoro-1,3,2-dioxaborines 2a–i
with anions
Stock solutions of the 2,2,-difluoro-1,3,2-dioxaborines 2a–i (5 μm) and
solutions of sodium cyanide, chloride, fluoride, phosphate, nitrite,
nitrate and sulfate (0.5 mm) were freshly prepared in MeCN/H2O (4:1).
Absorption spectra of 2a–i were recorded in the absence of any ani-
ons and in the presence of a 100-molar excess of sodium cyanide,
chloride, fluoride, phosphate, nitrite, nitrate or sulfate. For the pH
study, the solutions of 2a were prepared in MeCN/H2O (4:1).
[9] Ran, C.; Zhao, W.; Moir, R. D.; Moore, A. non-conjugated small
molecule FRET for differentiating monomers from higher
molecular weight amyloid beta species. PLoS One 2011, 6,
e19362.
[10] Sui, Z.; Salto, R.; Li, J.; Craik, C.; Montellano, P. R. O. Inhibition
of the HIV-1 and HIV-2 proteases by curcumin and curcumin
boron complexes. Bioorg. Med. Chem. 1993, 1, 415–422.
[11] D’Aleo, A.; Felouat, A.; Heresanu, V.; Ranguis, A.;
Chaudanson, D.; Karapetyan, A.; Giorgi, M.; Fages, F.
Two-photon excited fluorescence of BF2 complexes of curcumin
analogues: towards NIR-to-NIR fluorescent organic nano-
particles. J. Mater. Chem. C 2014, 2, 5208–5215.
Acknowledgments: SDR thanks Ministry of Human
Resource Development, Government of India for fellow-
ship. KNR thanks UGC for UGC-BSR Faculty Fellowship.
The authors thank V.S. Keerthi, G.K. Athira, V.R. Divya and
G. Rekhakrishnan for help in preliminary experimenta-
tions. The authors also thank SAIF-STIC at CUSAT, Kochi,
NIIST Trivandrum and IISER Trivandrum, for elemental
analysis, NMR and mass spectra.
[12] Bai, G.; Yu. C.; Cheng, C.; Hao, E.; Wei, Y.; Mu, X.; Jiao, L.
Syntheses and photophysical properties of BF2 complexes of
curcumin analogues. Org. Biomol. Chem. 2014, 12, 1618–1626.
[13] Felouat, A.; D’Aleo, A.; Fages, F. Synthesis and photophysical
properties of difluoroboron complexes of curcuminoid deriva-
tives bearing different terminal aromatic units and a meso-aryl
ring. J. Org. Chem. 2013, 78, 4446–4455.
[14] Babu, K. V. D.; Rajasekharan, K. N. Simplified conditions for
the synthesis of curcumin I and other curcuminoids. Org. Prep.
Procedures Intl. 1994, 26, 674–677.
[15] Kiran, M. S.; Sameerkumar, V. B.; Viji, R. I.; Sherin, G. T.;
Rajasekharan, K. N.; Sudhakaran, P. R. Opposing effects of
curcuminoids on serum stimulated and unstimulated angio-
genic response. J. Cell. Physiol. 2008, 215, 251–264.
[16] Mayadevi, M; Sherin, D. R.; Keerthi, V. S.; Rajasekharan, K. N.;
Omkumar, R. V. Curcumin is an inhibitor of calcium/calmodulin
dependent protein kinase II. Bioorg. Med. Chem. 2012, 20,
6040–6047.
References
[1] Cogné-Laage, E.; Allemand, J. -F.; Ruel, O.; Baudin, J. -B.;
Croquette, V.; Blanchard-Desce, M.; Jullien, L.
Diaroyl(methanato)boron difluoride compounds as
medium-sensitive two-photon fluorescent probes.
Chem-Eur. J. 2004, 10, 1445–1455.
[2] Galer, P.; Korosec, R. C.; Vidmar, M.; Sket, B. Crystal structures
and emission properties of the BF2 complex 1-phenyl-3-(3,5-
dimethoxyphenyl)-propane-1,3-dione: multiple chromisms,
aggregation- or crystallization-induced emission, and the self-
assembly effect. J. Am. Chem. Soc. 2014, 136, 7383–7394.
[3] Xu, S.; Evans, R. E.; Liu, T.; Zhang, G.; Demas, J. N.;
Trindle, C. O.; Fraser, C. S. Aromatic difluoroboron β-diketonate
complexes: effects of π-conjugation and media on optical
properties. Inorg. Chem. 2013, 52, 3597–3610.
[4] Fraser, C. L.; Zhang, G.; Payne, S. J.; Demas, J. N.; Pfister, A.;
Kooi, S. E.; Chen, Y. J.; St. Clair, T. L.; Lee, Y. -J. Light emitting
boron biomaterials. Polym. Mater. Sci. Eng. 2008, 98, 24–27.
[17] Venkateswarlu, S.; Ramachandra, M. S.; Subbaraju, G. V.
Synthesis and biological evaluation of polyhydroxycurcumi-
noids. Bioorg. Med. Chem. 2005, 13, 6374–6380.
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