Synthesis and photo-property of 2-cyano boron-dipyrromethene and the application for detecting fluoride ion

Article abstract of DOI:10.1016/j.tet.2015.10.081

Three 2-cyano boron-dipyrromethene (BODIPY) based derivatives (CB1-CB3) have been synthesized and characterized. The photophysical properties of these compounds are investigated by means of UV/Vis absorption and fluorescence spectroscopy. CB1-CB3 exhibit

Full text of DOI:10.1016/j.tet.2015.10.081

Tetrahedron 71 (2015) 9611e9616
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Synthesis and photo-property of 2-cyano boron-dipyrromethene
and the application for detecting fluoride ion
a
,
a
b
a
a
*
Jianbo Wang , Qianshou Zong , Qingqing Wu , Jinjin Shen , Fengyuan Dai ,
Chenjun Wu
a
a
College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, China
Jiangsu Nhwa Pharmaceutical Co., Ltd, Xuzhou 221000, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 August 2015
Received in revised form 24 October 2015
Accepted 29 October 2015
Available online 31 October 2015
Three 2-cyano boron-dipyrromethene (BODIPY) based derivatives (CB1eCB3) have been synthesized and
characterized. The photophysical properties of these compounds are investigated by means of UV/Vis
absorption and fluorescence spectroscopy. CB1eCB3 exhibit small Stokes shift and high fluorescence
quantum yield. Noticeably, CB2 with styrene moieties at 5-position of BODIPY displays absorption al-
ternation with maximum of 120 nm red-shift upon addition of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)
as a base, giving remarkable color change which can be detected by naked eye. Meanwhile, the com-
pound CB3 shows high selectivity toward fluoride ion via fluorescence quenching mechanism by release
of the masked phenolate form of CB2 through fluoride ion induced deprotection reaction. It also exhibits
fast signal response time (30 s) and excellent selectivity over other competing analytes, making it a good
candidate as colorimetric sensor for fluoride sensing.
Keywords:
Bodipy derivatives
Fluoride ion
Colorimetric sensor
High selectivity
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
broad fields such as fluorescent dyes, cation and anion sensors,
drug delivery agents, light harvesting systems and photodynamic
7
As anions play a fundamental and important role in many
chemical and biological processes, the design and synthesis of
probe for the detection of anions with high selectivity and sensi-
therapy.
Several new BODIPY compounds with functionalization at all
the positions of BODIPY core have been synthesized.
ample, all position of BODIPY compound can be halogenated and
given the halogenated BODIPYs which have been used as building
blocks to synthesize different types of new BODIPY derivatives
through metal-catalyzed cross-coupling reaction and nucleophilic
substitution reaction. Recently, Boens et al. developed the syn-
thesis of arylated BODIPY by the metal-catalyzed direct CeH ary-
lation. The methyl groups at 3, 5-positions of BODIPYs can be
subjected to the Knoevengal reaction with electron-rich aromatic
aldehydes owing to their strong nucleophilic character, generating
8
e13
For ex-
1
tivity have attracted intensive interest. Fluoride ion has been
proved to be very important anion in dental care and in the treat-
2
ment of osteoporosis. However, excessive intake of fluoride ion
can cause fluorosis on human and animal kidney damage, leading
3
8
to urinary tract stones. In this context, many colorimetric and
4
e6
fluorescent fluoride probes have been designed and reported.
9
For those various sensors, hydrogen bonding between proton do-
nor and fluoride4 and fluoride-boron interaction between
5
organoboron-derivatives and fluoride have been frequently in-
10
vestigated and utilized for the recognition. Meanwhile, the
conjugated styrene moieties on BODIPYs. Ziessel and co-workers
reaction-based sensor based on the formation of FeSi bond has also
been designed and applied with very high selectivity.
reported a library of highly stable C-BODIPY and E-BODIPY dyes by
C or O atoms subunits in place of the usual fluorine atoms. The
6
11
Recently, boron-dipyrromethene (BODIPY) derivatives have
attracted much interest due to their unique photophysical proper-
ties, such as strong absorption in the visible and near-IR ranges,
high fluorescence quantum yield and excellent photo-stability. The
easy synthesis, potential for derivatization and excellent photo-
physical properties of BODIPY compounds make it be utilized in
formyl groups can be introduced at 2-/6- position of BODIPY by
3
using POCl /DMF reagents and further transformed for the syn-
12
thesis of new BODIPY derivatives. The amines and carboxylic acid
groups can also be directly introduced to BODIPY, which can be
13
used for ligation reaction with proteins or DNA-derivatives.
Therefore, a newly modified BODIPY with a novel functional
group would be interesting and useful in organic synthesis and
sensing applications.
*
Corresponding author. E-mail address: wjb4207@mail.ustc.edu.cn (J. Wang).
http://dx.doi.org/10.1016/j.tet.2015.10.081
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
0

9612
J. Wang et al. / Tetrahedron 71 (2015) 9611e9616
Cyano as a special and versatile functional group can be hy-
2.2. Absorption and fluorescence properties of compounds
CB1eCB3
drolyzed to carboxylic acid and reduced to aminies. As a result, the
Cyano-modified BODIPY can be activated and applied to the bi-
ological labeling. The meso-cyano modified BODIPYs have been
synthesized and their fluorescence and absorbance spectra show
approximate 60 nm red-shift comparing with simply alkyl-
substituted BODIPYs, which is attributed to the net stabilization
The absorption spectra and fluorescence spectra of compounds
CB1eCB3 were performed in various solvents. As showed in Fig. 1,
Fig. S1e2 and Table 1, these CN-modified compounds CB1, CB2
and CB3 show the typical BODIPY platform photophysical char-
acteristics with a narrow and strong absorption band around 480
and 550 nm, respectively, which is corresponded to the S0eS1
transition. The absorption maximum of CB1 exhibits a slight
hypsochromic shift with about 17 nm when solvent is changed
from toluene (492 nm) to acetonitrile (475 nm). Similarly, the
emission spectrum also shows minor solvent-dependent shift
with decreased fluorescence quantum yields (from 0.74 in toluene
to 0.59 in methanol), which is consistent with the general be-
havior of other BODIPY chromophores. Due to the styrene sub-
stitution at the 5-position of BODIPY, the absorption spectra of
CB2 and CB3 have absorption maximum at 550 nm and the
maximum shift of absorbance spectra is only 6 nm and 19 nm for
CB2 and CB3, respectively. Similar to their absorption spectra,
their fluorescence spectra also show minor solvent-dependent
shift and the maximum emission wavelength in 560e580 nm
range.
of the LUMO level, hence the decrease of energy gap induced by the
cyano group.1
4,7b
However, this spectral phenomenon is not ob-
15
served in the reported 2, 6-cyano modified BODIPYs. In this work,
we have synthesized three 2-cyano-modified asymmetric BODIPY
derivatives CB1eCB3 through CF
3
COOH-catalyzed condensation of
5
-formyl-4-methyl-pyrrole-3-carbonitrile with 2, 4-dimethyl pyr-
role (Scheme 1). A styrene moiety at Bodipy 5-position in CB2 is
introduced by the Knoevengal reaction between CB1 and an aro-
matic aldehyde. All three compounds display good chemical sta-
bility and fluorescence properties. The CB2 is converted to the
phenolate form from the neutral phenol states when the strong
base (DBU) is added, which generates remarkable color change and
fluorescence decrease. CB3 shows high selectivity for detecting
fluoride ion as colorimetric sensor based on the de-protective re-
action. On the other hand, the cyano group in CB3 renders the SieO
band cleavage by fluoride faster to realize short response time.
Scheme 1. Synthesis routes of compounds CB1, CB2 and CB3.
2
2
. Result and discussion
The un-cyano substituted BODIPY compound B118 and B2 were
also synthesized and their photo properties were studied. As shown
in Fig. S3eS4 and Table S1, compound B1 and B2 exhibit a similar
narrow and strong absorption band around 490 and 560 nm, re-
spectively. Compared with B1 and B2, 2-CN BODIPY compounds
CB1 and CB2 show a slight blue-shift with 10 nm and the larger
Stokes shifts (31 nm in MeOH for CB2), as observed from the ab-
sorbance and fluorescence spectra, which is attribute to the pres-
ence of the cyano group.
Due to the acidic phenol group in CB2, the deprotonation re-
action in the presence of organic base could occur. It was found that
the conversion of phenol group to phenolate form in CB2 could be
achieved by simply adding DBU (1,8-diazabicyclo[5.4.0]undec-7-
ene) in solution, the UV/Vis absorption spectra display a quite
large red shift. As showed in Fig. 2, CB2 treated with 10 equiv of
.1. Synthesis of compound CB1eCB3
Three 2-cyano BODIPY derivatives were synthesized accord-
ing to the procedure shown in Scheme 1. The compound 2 was
synthesized by using POCl /DMF reaction with 4-methyl-pyrrole-
-carbonitrile (compound 1) as the starting material. The
3
16
3
Bodipy derivative CB1 was obtained through the TFA-catalyzed
condensation reaction of 2 with 2,4-dimethyl-pyrrole according
to BODIPY formation procedure using Et N and BF $Et O. The
3 3 2
compound CB2 was obtained by condensation reaction of the
compound CB1 with 4-hydroxybenzaldehyde under AcOH and
pyridine. Finally, compound CB3 was obtained by the reaction of
compound CB2 with tert-butyldimethylchlorosilane (TBDMSCl)
in the presence of imidazole. Those compounds were further
3
DBU in CH CN exhibits obvious absorption alternation with maxi-
mum red-shift from 545 nm to 653 nm, resulting in remarkable
solution color change from orange to blue. It is attributed to
1
13
confirmed and characterized by H, C NMR spectra and HR-MS
measurements.

J. Wang et al. / Tetrahedron 71 (2015) 9611e9616
9613
Fig. 1. Normalized absorption spectra and fluorescence spectra of compound CB1 in different solvent.
Table 1
Spectroscopic data for compounds CB1eCB3 in various solvents
2.3. TBDMS deprotective reaction based response of CB3 to
fluoride ion
a
2
-CN BODIPY
Solvent
Toluene
l
abs/nm
l
em/nm
Stokes shift/nm
F
f
Fig. 3 displays the UVevis absorption titration of compound CB3
with various amount of fluoride ion in CH CN at room temperature.
CB1
492
483
482
476
475
551
555
546
545
562
553
550
542
543
507
498
500
495
495
570
582
577
573
578
575
571
566
570
15
15
18
19
20
19
27
31
28
16
22
21
24
27
0.74
0.63
0.64
0.59
0.63
0.38
0.23
0.18
0.29
0.50
0.46
0.57
0.45
0.47
CH
2
Cl
2
3
THF
MeOH
MeCN
With increasing equivalence of fluoride ion (using TBAF), the in-
tensity of the absorption maximum at 543 nm gradually decreased,
concomitant with the formation of a new band centered at 653 nm,
with an isosbestic point at 570 nm. Correspondingly, the absorption
alternation of 110 nm red-shift results in the solution distinct color
change from pink to blue, which can be directly observed by naked
eyes. The absorption band at 653 nm is similar to that characteristic
absorption of phenolate form of CB2 (Fig. 2), where is attributed to
CB2
CB3
CH
2
Cl
2
THF
MeOH
MeCN
Toluene
CH
2
Cl
2
THF
MeOH
MeCN
ꢀ
the F promoted deprotection of CB3 to generate phenolate form as
that of CB2.
a
The V
f
values was determined using fluorescein (0.85 in 0.1N NaOH)17 as
a standard.
occurrence of a strong intramolecular charge transfer (ICT) from
phenolate unit to the conjugated BODIPY core. Similar to the re-
ported BODIPYs bearing phenolic subunits, such large red-shift
results in a decrease in the emission intensity. Based on the
above results, compound CB3 is designed as colorimetric sensor for
detecting fluoride by fluoride-induced SieO bond cleavage
reaction.
Fig. 3. The absorption spectra change of compound CB3 (5
concentration of TBAF (0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 30 equiv) in CH
m
M) with various
CN.
3
3
The fluorescence response of CB3 in CH CN toward various
amount of fluoride ion was also performed at room temperature. As
shown in Fig. 4, upon the addition of TBAF, the fluorescence in-
tensity at 570 nm was remarkably decreased, which was almost
ꢀ
linearly quenched with increasing added amount of F and 95% of
the fluorescence intensity was quenched upon addition of about
2
5 equiv of fluoride ion. This result originates from the formation of
ꢀ
non-emissive phenolate form of CB2 by the F promoted depro-
tection of CB3.
3
Fig. 2. The Normalized absorption spectra of compound CB2 in CH CN containing no
and organic base DBU (10 equiv).

9614
J. Wang et al. / Tetrahedron 71 (2015) 9611e9616
Fig. 4. The fluorescence spectra change of compound CB3 (5
mM) with various
concentration of TBAF (0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 28, 30 equiv) in CH
Inset: fluorescence intensity changes (at 570 nm) of CB3 with various amounts of F .
3
CN.
ꢀ
Kinetics profile of the fluorescence response of CB3 toward
fluoride ion was studied by time-dependent fluorescence spectra.
As is shown in Fig. 5, the quenching of fluorescence-intensity is
largely dependent on the concentration of fluoride ion in the so-
ꢀ
lution at room temperature. The F promoted de-protection maybe
it is an equilibrium, since less equivalence did not promote further
ꢀ
fluorescence quenching after 2 min. As a result, large excess of F
anion is necessary to drive the equilibrium to the right, afforded
a quicker and more dramatic fluorescent decrease response. The
CB3 didn’t show any noticeable change in the emission intensities
ꢀ
at 563 nm in the absence of F within 5 min. In contrast, CB3 was
ꢀ
quantitatively consumed in the presence of 25 or 30 equiv of F
within 30 s and the observed rate constant (kobs) was obtained to be
ꢀ
1
0
.14 or 0.18 s , respectively, which is faster than the reported
ꢀ
6b
ꢀ
Fig. 6. (a) The absorption spectra of compound CB3 (5
m
M) with F (25 equiv) and
3
compound. Therefore, CB3 for the detection of F in CH CN could
be achieved in 30 s at room temperature.
ꢀ
ꢀ
ꢀ
ꢀ
2ꢀ
ꢀ ꢀ ꢀ
other anions (25 equiv) including Cl , Br , I , H
CH
presence of 25 equiv of various anions in CH
2
PO
4
, HPO
4
, N
M) in the absence and
3 3
, NO and OH in
3
CN. (b) The fluorescence intensity at 570 nm of CB3 (5
m
ꢀ
ꢀ
ꢀ
ꢀ
3
CN: 1, free; 2, F ; 3, Cl ; 4, Br ; 5, I ; 6,
ꢀ ꢀ ꢀ ꢀ
2 4 3 3
H PO ; 7, N ; 8, NO ; 9, OH .
ꢀ
was only observed with the addition of F , whereas the addition of
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
various other anions such as Cl , Br , I , H
2
PO
4
, N
3
, NO
3
and OH
did not show any change in the absorption spectra. Meanwhile, the
color of CB3 solution changed from orange to blue with addition of
ꢀ
F
and the other anions didn’t induce any color change as showed
in Fig. 7. The fluorescence response of CB3 toward various anions is
Fig. 5. The time dependent of fluorescence intensity change at 570 nm of compound
CB3 (5 M) with different equiv of TBAF in CH CN.
m
3
The selectivity of compound CB3 toward fluoride ion is im-
pressively high due to the specific reactivity of SieO band cleavage
induced with F . As shown in Fig. 6a, the large absorption red-shift
Fig. 7. Colorimetric changes (up) and Fluorescence photographs (down) of compound
CB3 (5 mM) with 25 equiv of various anions in CH CN.
3
ꢀ

J. Wang et al. / Tetrahedron 71 (2015) 9611e9616
9615
shown in Fig. 6b. CB3 showed strong fluorescence intensity at
70 nm, and the fluorescence change didn’t take place upon ad-
21.2 mmol) and BF
reaction was stirred for 5 h. The mixture was washed with water
and brine. The organic layers was dried Na SO , filtered and
3
$OEt
2
(3.1 ml, 24.2 mmol) were added and the
5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
dition of 25 equiv of Cl , Br , I , H
2
PO
4
, N
3
, NO
3
and OH . Only the
2
4
ꢀ
introduction of
F
resulted in the remarkable fluorescence
evaporated. The residue was purified by silica gel column chro-
quenching and this response could also be observed by naked eyes
under a hand-held UV lamp from Fig. 7. These results indicate the
excellent selectivity of CB3 towards F over other competitive
matography to give compound CB1 (0.36 g, 47%) as black solid.
1
R
f
¼0.33 (ethyl acetate/petroleum ether 1/2). H NMR (400 MHz,
ꢀ
CDCl
3H), 2.34 (s, 3H). C NMR (100 MHz, CDCl
39.0, 138.3, 129.9, 123.4, 122.0, 114.9, 99.7, 15.6, 11.6, 10.4. IR (KBr,
3
): d 7.76 (s, 1H), 7.22 (s, 1H), 6.31 (s, 1H), 2.62 (s, 3H), 2.40 (s,
13
anions.
3
): d 167.7, 148.2, 139.5,
1
ꢀ1
3
. Conclusion
cm ): 3432 (m), 2926 (m), 2219 (m), 1611(s), 1415 (s), 1260 (s),
þ
1090 (s), 972 (m). FTMS (EI) calcd for M
13 12 3 2
C H N BF : 259.1092,
In summary, we have synthesized and investigated three 2-
found 259.1088.
cyano modified asymmetric BODIPY derivatives CB1eCB3, which
show typical photophysical behavior of BODIPY derivatives with
small Stokes shift and high fluorescence quantum yield. The CB2
turns into the phenolate form upon adding base (DBU) and exhibits
remarkable color change and fluorescence decrease owing to the
strong intramolecular charge transfer. Accordingly, the CB3 is
designed and applied as a colorimetric sensor for detecting fluoride
4.2.3. Synthesis of compound CB2. To a stirred solution of com-
pound CB1 (0.17 g, 0.66 mmol) and 4-hydroxybenzaldehyde (0.1 g,
3 3
0.79 mmol) in CH CN (10 ml) was added CH COOH (0.26 g) and
ꢁ
pyridine (0.33 g). The mixture was stirred at 70 C for 30 min where
the reaction was completed by TLC monitored. Then the solvent
was evaporated by vacuum. Water (20 ml) was added and the so-
lution was extracted with EtOAc (15 mlꢂ3). The combined organic
ꢀ
ion. CB3 shows excellent selectivity owing to the specific F
deprotective reaction and rapid response time (30 s) due to the
electron-withdrawing cyano group in BODIPY core. These cyano-
substituted BODIPY can be further modified and show their po-
tential in the biological labeling in our following work.
2 4
layers was washed with brine, dried over Na SO and evaporated
under vacuum. The residue was purified by silica gel column
chromatography to give compound CB2 (0.11 g, 46%) as violent
1
solid.
400 MHz, DMSO-d
1H), 7.86 (s, 1H), 7.56 (d, J¼8.4 Hz, 2H), 7.24e7.29 (m, 2H), 6.90 (d,
R
f
¼0.21 (ethyl acetate/petroleum ether 1/1).
H NMR
(
6
):
d
10.35 (s, 1H), 8.14 (s, 1H), 7.93 (d, J¼16 Hz,
4
4
. Experimental
13
J¼8.4 Hz, 2H), 2.41 (s, 3H), 2.39 (s, 3H). C NMR (100 MHz, DMSO-
): 163.0, 161.3, 148.0, 145.8, 140.0, 139.0, 136.9, 131.0, 130.5,
26.8, 121.0, 120.1, 116.8, 116.3, 115.6, 113.9, 11.8, 10.4. IR (KBr, cm ):
.1. Reagents and instrumentation
Solvents for organic synthesis were reagent grade, and were
d
1
6
d
ꢀ
1
3431 (m), 2924 (m), 2224 (m), 1601 (s), 1418 (s), 1265 (s), 1152 (m),
dried prior to use. 4-Methyl-pyrrole-3-carbonitrile was prepared as
1066 (m). FTMS (ESI) calcd for [MþNa]þ
20 3 2
C H16ON BF Na:
16
described in the literature. Other chemicals were purchased from
commercial sources and used as received. Double distilled water
386.1250, found 386.1242.
1
13
was used throughout the experiments. H and C NMR spectra
were measured in CDCl with a Varian operating at 400 MHz and
00 MHz, respectively and chemical shifts were reported in ppm
4.2.4. Synthesis of compound CB3. A mixture of compound CB2
(80 mg, 0.22 mmol), tert-butyldimethylchlorosilane (TBDMSCl,
66 mg, 0.44 mmol) and imidazole (45 mg, 0.66 mmol) in DMF
3
1
using tetramethylsilane (TMS) as internal standard. FT-IR spectra
were measured with a Bruker Vector22 Infrared Spectrometer.
Mass spectra were obtained with a Micromass GCF TOF mass
spectrometer. UVevis absorption and fluorescence emission spec-
tra were performed at room temperature with a Shimadzu UV-
2
(5 ml) was stirred at room temperature for 6 h under N . After the
reaction completed, water (20 ml) was added and the solution was
extracted with EtOAc (15 mlꢂ3). The combined organic layers was
2 4
washed with brine, dried over Na SO and evaporated under vac-
uum. The residue was purified by silica gel column chromatography
to give compound CB3 (45 mg, 43%) as violent solid. R
¼0.46 (ethyl
acetate/petroleum ether 1/2). H NMR (400 MHz, CDCl ): 7.79 (s,
2
450 UVevis spectrometer and Shimadzu RF 5301 PC spectro-
f
1
photometer, respectively. Fluorescence quantum yield was de-
3
d
termined using fluorescein (
a reference.
F
f
¼0.85 in 0.1N NaOH) [17] as
1H), 7.55 (d, J¼8.8 Hz, 2H), 7.47 (s, 2H), 7.11 (s, 1H), 6.89 (d, J¼8.8 Hz,
2H), 6.85 (s, 1H), 2.41 (s, 3H), 2.37 (s, 3H), 0.99 (s, 9H), 0.24 (s, 6H).
1
3
Z 3
C NMR (100 MH , CDCl ): d 162.6, 158.7, 146.4, 143.7, 139.6, 138.3,
4
.2. Synthesis
136.9, 130.3, 130.2, 128.5, 120.8, 118.9, 118.8, 115.6, 115.2, 99.3, 25.6,
ꢀ
1
1
8.3, 11.7, 10.4, ꢀ4.3. IR (KBr, cm ): 3337 (m), 2927 (m), 2221 (m),
þ
4.2.1. Synthesis of compound 2. POCl
3
(4 ml, 43 mmol) was added
1610 (s), 1419 (s), 1266 (s), 1156 (m). FTMS (ESI) calcd for [MþNa]
dropwise to DMF (3.4 ml, 43 mmol) in an ice bath for 5 min, then
the solution was stirred for additional 1 h at 25 C. Compound 1
C
26
H30ON
3
2
BF SiNa: 500.2116, found 500.2112.
ꢁ
(
3 g, 28.3 mmol) in DMF (12 ml) was added slowly. The mixture was
Acknowledgements
ꢁ
stirred at 25 C for 1 h, then poured into ice water. The precipitated
light yellow solid was collected by filtration and purified by silica
This work was supported by Zhejiang Provincial Natural Science
Foundation of China (Grant No. LQ15B060005) and the National
Natural Science Foundation of China (Grant No. 21302063).
gel column chromatography to give compound 2 (2.8 g, 74%) as
1
white solid. R
f
¼0.30 (ethyl acetate/petroleum ether 1/2). H NMR
(
2
400 MHz, CDCl
3
):
d
9.80 (s, 1H), 9.70 (s, 1H), 7.45 (d, J¼2.8 Hz, 1H),
): 178.0, 134.4, 130.2, 129.6,
14.1, 97.8, 9.4. IR (KBr, cm ): 3253 (m), 2225 (m),1654 (s), 1417 (s),
.51 (s, 3H). 13C NMR (100 MHz, CDCl
d
3
Supplementary data
ꢀ1
1
1
þ
361 (m), 800 (s). FTMS (EI) calcd for M C H N O: 134.0480, found
7 6 2
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.10.081.
134.0480.
4
.2.2. Synthesis of compound CB1. To a stirred solution of com-
References and notes
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3
2
2
3
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