A simple and catalyst free one pot access to the pyrazolone fused 2,8-dioxabicyclo[3.3.1]nonanes

Article abstract of DOI:10.1039/c4ra07278b

Synthesis of a series of novel aryl and heteroaryl fused 2,8-dioxabicyclo[3.3.1]nonanes (3) was accomplished by one pot, catalyst free reaction of 2-hydroxy chalcone (1) with 3-trifluoromethyl substituted pyrazolone (2) in xylene at reflux temperature. Th

Full text of DOI:10.1039/c4ra07278b

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A simple and catalyst free one pot access to the
pyrazolone fused 2,8-dioxabicyclo[3.3.1]nonanes†
Cite this: RSC Adv., 2014, 4, 35009
Chiranjeevi Bingi,a Narender Reddy Emmadi,a Madhu Chennapuram,a
b
ac
*
Jagadeesh Babu Nanubolu and Krishnaiah Atmakur
Synthesis of a series of novel aryl and heteroaryl fused 2,8-dioxabicyclo[3.3.1]nonanes (3) was accomplished
by one pot, catalyst free reaction of 2-hydroxy chalcone (1) with 3-trifluoromethyl substituted pyrazolone
(2) in xylene at reflux temperature. The role of the trifluoromethyl functional group in formation of 3 was
confirmed by comparative studies with 3-methyl substituted pyrazolones (2c,d) and the outcome is
presented.
Received 1st May 2014
Accepted 29th July 2014
DOI: 10.1039/c4ra07278b
www.rsc.org/advances
Several reports have appeared on the construction of 2,8-
dioxabicyclo[3.3.1]nonane frame work with varied structural
analogues. For example, Manolov6 reported 1-phenyl or
1. Introduction
The 2,8-dioxabicyclo[3.3.1]nonane is a unique bicyclo frame-
work which is widely found in natural products and biologically
active compounds.1 Trogers base,2 a prominent methylene
bridged bicyclic compound and its derivatives have been widely
employed as molecular tweezers,3 ion receptors4 and high
affinity DNA targeting uorescent supramolecular scaffolds5
owing to their rigidity. Similarly, 2,8-dioxabicyclo[3.3.1]nonanes
e.g. dracoavan C, dracoavan D and procyanidin A1 (Fig. 1) an
important methylene bridged bicyclic compounds have been
found in medicinal plant sources.
methyl 2,8-dioxabicyclo[3.3.1]nonanes by a base catalyzed
reaction of 3-benzoyl or acetyl coumarin with 4-hydroxy
coumarin. Yang7 reported the reaction of 2-phenyl chroman-
4-ol with 4-hydroxy coumarin catalyzed by aluminium chlo-
ride. Weinges8 described a three step sequence to bicyclic
core by reacting 2-benzyloxy chalcone and 2-benzyloxy
phenyl magnesium bromide, Meetsma9 reported 1-methyl
substituted 2,8-dioxa bicyclo[3.3.1]-nonanes from b-napthol,
salicilaldehyde and excess ethyl acetoacetate catalyzed by
Lewis acid and more general methods10 were appeared to
access this frame work by condensing avylium salts and
polyphenols.
More recently, Anxin Wu11 described the stereo selective
synthesis of 2,8-dioxabicyclo[3.3.1]nonanes by the reaction of
3-(2-hydroxy phenyl)-1-phenyl prop-2-en-1-one with 4-hydroxy
coumarin, 1,3-dione and also with 1,4-napthaquinone. Min
Shi12 reported the construction of [3.3.1]bicyclic ketals by
enantioselective Pd(II) catalyzed reaction of 2-hydroxy phenyl
boronic acid and 2-hydroxy chalcone.
Guodong Yin13 reported the Ag(OTf) catalyzed synthesis of
di-aryl fused [3.3.1]bicyclic nonanes by reacting 2-hydroxy
chalcones with napthols and also with substituted phenols.
The latest report14 was by the reaction of 2-hydoxy chalcones
with napthols catalyzed by (D,L)-10-camphorsulfonic acid to
furnish diaryl fused 2,8-dioxabicyclo[3.3.1]nonanes. Thus a
great deal of effort has been done to prepare these deriva-
tives. However all these reports are on diaryl fused bicyclo
nonanes which are sometime requiring using expensive
catalysts.
Fig.
products.
1 2,8-Dioxabicyclo[3.3.1]nonane containing bioactive natural
aDivision of Crop Protection Chemicals, CSIR-Indian Institute of Chemical Technology,
Tarnaka, Hyderabad 500 007, India. E-mail: srikrishnua@yahoo.com; Tel:
+91-40-27191436
bLaboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology,
On the other hand, pyrazolone is a key structure in
numerous compounds of therapeutic importance and have
been the focus of medicinal chemists because of the
outstanding pharmacological properties shown by several of its
Tarnaka, Hyderabad 500 007, India
cAcSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
† Electronic supplementary information (ESI) available. CCDC 994173. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c4ra07278b
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Table 1 Optimizationb of reaction conditions for synthesis of 3aa
derivatives e.g. ampyrone, metanizole etc. Further, pyrazolone is
a constituent structural feature of many NSAIDS clinically
useful in the treatment of arthritis and other musculo skeletal
and joint disorders.15 Therefore, the investigation on the
chemistry of pyrazolones have been, and continuous to be one
of the most active area of heterocyclic chemistry. Realising the
importance of pyrazolones and the signicance of 2,8-dioxabi-
cyclo[3.3.1]nonanes in one way, nowadays keen research
interest on synthesis and derivatization of complex structural
motifs with an attached bicyclo[3.3.1]nonane frame work16 on
the other way, we planned to synthesize a new series of 2,8-
dioxabicyclo[3.3.1]nonane compounds by fusing 2-hydroxy
chalcones (1) with triuoromethyl substituted pyrazolones (2).
Additionally, presence of uorine, especially triuoromethyl
group at a specied position in a molecule alters the reactivity
because of its strong electron withdrawing character, lip-
ophilicity and metabolic stability. In this context, the literature
survey at this stage revealed that, no reports are available on the
aryl and hetero aryl fused 2,8-dioxabicyclo[3.3.1]nonanes. With
this background and also as a part of our continuous endeavour
to synthesize new bio-active molecules,17 we herein report for
the rst time an aryl and pyrazolone fused 2,8-dioxabicyclo-
[3.3.1]nonane (3) derivatives in a one pot reaction without any
catalyst.
Entry
Solvent
Catalyst
Time (h)
Yieldc (%)
1
2
3
4
5
6
7
8
Methanol
Ethanol
n-PrOH
1,4-Dioxane
Water
—
—
—
—
24
24
10
24
8
10
10
8
8
8
4
4
20
34
58
36
55
59
50
61
62
71
81
76
72
67
74
71
—
n-PrOH
CuCl2$2H2O
CuCl2$2H2O
—
Cu(OTf)2
CuCl2$2H2O
—
CuCl2$2H2O
Cu(OTf)2
Zn(OTf)2
CSA
1,4-Dioxane
Toluene
Toluene
Toluene
p-Xylene
p-Xylene
p-Xylene
p-Xylene
p-Xylene
p-Xylene
9
10
11
12
13
14
15
16
4
4
8
8
CuBr
a
b
—: no catalyst. All the reactions were performed with 2-hydroxy
chalcone (1a, 0.1 mmol), 3-triuoromethyl pyrazolone (2a, 0.1 mmol)
and catalyst (30 mol%) in appropriate solvent were reuxed under
2. Results and discussions
Before testing the feasibility of our hypothesis to construct the
2,8-dioxabicyclo[3.3.1]nonane framework with aryl and hetero
aryl moieties, 2-hydroxy chalcone (1a) was prepared by known
c
above mentioned. Yield refers to pure products aer column
chromatography.
procedure18 and
a
model reaction was attempted with
compound (1a) and pyrazolone (2a) in methanol and ethanol
separately without any catalyst (Table 1). However, formation of releasing groups could not make much impact when compared
the desired product 3 was observed in very poor yields upon with simple aryl groups. Further, aliphatic groups such as
long reuxing. Further, the same reaction was studied inde- methyl, ethyl and isobutyl adjacent to a,b-unsaturated ketone
pendently in n-propyl alcohol, 1,4-dioxane and water. All these on 1 also gave the products 3m–o in 70% yields under these set
studies resulted in formation of bicyclic compound 3 in poor of reaction conditions.
yields.
Structure of compound 3 was well characterized by NMR, IR,
Continued studies to improve the yields of 3, by employing Mass spectrometry and a representative sample 3a was unam-
Lewis acid catalysts (entry 6, 7, Table 1) resulted in formation of biguously conrmed by X-ray crystallography19 (Fig. 2).
3 in moderate yields. Subsequently, next reaction was con-
In order to nd out the role of –CF3 if any on the formation of
ducted in high boiling solvent like toluene at reux temperature 3, this protocol was veried by reacting 2-hydroxy chalcone (1a)
and interestingly yields of 3 were improved to 61%. When the with 3-methyl-1-phenyl substituted pyrazolone (2c) (Scheme 1).
same reaction was conducted by employing Lewis acid catalysts Surprisingly, there was no formation of desired product 3.
(entry-9, 10, Table 1) a perceptible increase in yields 71% were Instead, only a Michael adduct 4 was observed in poor yields
observed. Next, the reaction was conducted in xylene medium at along with other unidentiable compounds. Further heating of
reux temperature. Surprisingly, yields of 3 were dramatically compound 4 also didn't lead to the desired product; instead it
improved to 81%. Subsequent studies by employing the Lewis decomposed into unidentiable compounds. This indicates the
acid catalysts in xylene medium as indicated in Table 1 could –CF3 inuence in formation of 3. To conrm this, compound 1a
not enhance the yields. Encouraged by the remarkable results was further reacted with 3-methyl pyrazolone (2d) under similar
obtained in xylene without any catalyst, the generality and scope set of reaction condition. However, it failed to produce either 3
of this protocol was explored by synthesizing a series of new or 4. This clearly indicates the –CF3 inuence in formation
compounds by varying the substitution (Table 2). A wide range product 3. Additionally, formation of 3t,u in high yields by the
of functional groups such as electron withdrawing and electron reaction of 2-hydroxychalcone with 3-triuoromethyl pyr-
releasing groups on 1 were well tolerated. However, the yields azolone (2b) without N-phenyl (aromatic) substitution
were varied. Compounds bearing electron withdrawing groups substantiate the remarkable inuence of –CF3.
gave the better yields and the compounds with electron
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Table 2 Scope of reaction between chalcones and 3-trifluoromethyl
pyrazolonesa,b
a
All the products were characterized by NMR, IR and mass
b
spectrometry.
Yield refers to pure products aer column
chromatography.
Inuence of –CF3 in formation of 3 can be explained by the
fact that, as a most electronegative atom, uorine has a very
strong effect on the acidity or basicity of nearby functional
groups.20–22 Thus, in case of 2a, due to the strong electron
withdrawing nature of –CF3, the methylene protons on C-4 may
becoming highly acidic resulting to enolize quickly and involve
in Michael addition, intramolecular cyclization followed by
water elimination to give the desired product 3 through either
path A or path B (Scheme 2). Experimental observation also
espouse this explanation as the formation of 3 was observed
directly not followed by the Michael adduct.
Scheme 1
Scheme 2 Plausible Mechanism for 3.
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by rotary evaporator and the leover residual solid mass was
washed with water and hexane to obtain the pure solid 2a.
4.2.1 1-Phenyl-3-(triuoromethyl)-1H-pyrazol-5(4H)-one (2a).
Yield 90%; Mp 185–186 ꢀC; IR (KBr): 3014, 1603, 1508, 1139, 995
cmꢁ1; 1H NMR (500 MHz, CDCl3 + DMSO-d6): d 7.75 (d, J ¼ 7.7 Hz,
2H), 7.46 (t, J ¼ 7.3 Hz, 2H), 7.33 (t, J ¼ 7.3 Hz, 1H), 5.82 (s, 1H)
ppm; 13C NMR (125 MHz, CDCl3 + DMSO-d6): d 152.0, 139.4 (q,
2JC–F ¼ 38.1 Hz), 136.5, 127.2, 125.2, 120.6, 119.7 (q, 1JC–F ¼ 268.8
Hz), 84.0 ppm; ESI-MS: m/z 229 [M + H]+.
4.2.2 3-(Triuoromethyl)-1H-pyrazol-5(4H)-one (2b). Yield
88%; Mp 210–212 ꢀC; IR (KBr): 3121, 2804, 1731, 1598, 1492,
1259, 985 cmꢁ1; 1H NMR (500 MHz, CDCl3 + DMSO-d6): d 5.65 (s,
1H) ppm; 13C NMR (125 MHz, CDCl3 + DMSO-d6): 153.9, 138.8
2
1
(q, JC–F ¼ 37.4 Hz), 120.1 (q, JC–F ¼ 267.9 Hz), 82.9 ppm; ESI-
MS: m/z 153 [M + H]+.
Fig. 2 ORTEP Diagram of compound 3a.
4.3 General procedure for the synthesis of 5-(aryl/alkyl)-3-
phenyl-1-(triuoromethyl)-3,11-dihydro-5,11-methanobenzo
[7,8][1,3]dioxocino[4,5-c]pyrazole derivatives (3)
3. Conclusions
A
mixture of 3-(2-hydroxyphenyl)-1-phenylprop-2-en-1-one
In closing, we have developed a simple, efficient and catalyst
free protocol to synthesize a series of novel 3-triuomethyl
substituted aryl and heteroaryl fused 2,8-dioxabicyclo[3.3.1]-
nonanes (3) for the rst time. Conrmed the–CF3 inuence on
the formation of 3 by comparative studies and provided
adequate reason. Higher yields, simple reaction condition and
environmentally benign synthesis are the advantages of this
protocol.
derivatives (1, 0.1 mmol) and 1-phenyl-3-(triuoromethyl)-1H-
pyrazol-5(4H)-one (2, 0.1 mmol) was heated to reux in p-xylene
(10 mL) while stirring in a round bottom ask. The solution
became homogeneous and dark brown on heating. Aer
completion of the reaction in 4 h, as indicated by TLC, it was
cooled to room temperature and solvent was removed by rotary
evaporator under reduced pressure. Then, the residue was
passed through column chromatography by eluting with 5–10%
(ethyl acetate–hexane) to furnish the pure compound.
4.3.1 3,5-Diphenyl-1-(triuoromethyl)-3,11-dihydro-5,11-
methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3a). Yield
81%; Mp 155–157 ꢀC; IR (KBr): 3065, 2953, 1952, 1596, 1481,
1227, 1131, 1015, 861, 757 cmꢁ1; 1H NMR (300 MHz, CDCl3): d
7.83–7.75 (m, 2H), 7.73–7.65 (m, 2H), 7.51–7.35 (m, 5H), 7.34–
7.16 (m, 3H), 7.10–6.98 (m, 2H), 4.28 (s, 1H), 2.56 (dd, J ¼ 13.6,
3.0 Hz, 1H), 2.35 (dd, J ¼ 13.6, 3.0 Hz, 1H) ppm; 13C NMR (75
MHz, CDCl3): d 151.9, 149.0, 139.5, 137.6, 137.1 (q, 2JC–F ¼ 37.9
Hz), 129.3, 129.0, 128.5, 128.2, 127.1, 126.9, 126.2, 125.6, 122.2,
121.4 (q, 1JC–F ¼ 270.1 Hz), 121.0, 116.4, 103.1, 101.8, 34.4, 27.1
ppm; ESI-MS: m/z 435 [M + H]+; HRMS (ESI) anal. calcd for
4. Experimental
4.1 General
Melting points were measured by CINTEX programmable
melting point apparatus and are uncorrected. 1H and 13C NMR
spectra of samples in CDCl3 and DMSO-d6 were recorded on
AVANCE-300 MHz and 500 MHz spectrometers. Chemical shis
(d) are reported relative to TMS (d ¼ 0.0) as the internal stan-
dard. Mass spectra were recorded in ESI spectrometers. All high
resolution mass spectra were recorded on QSTAR XL hybrid ms/
ms system (Applied Bio systems/MDS sciex, foster city, USA),
equipped with an ESI source (IICT, Hyderabad). IR was recorded
on Thermo Nicolet nexus-670 spectrometer with reference to
KBr. TLC was performed on Merck 60 F-254 silica gel plates. The
chemicals used in this work were obtained from commercial
channels and were used without purication.
C
25H18F3N2O2 m/z 435.1314 [M + H]+, found 435.1306.
4.3.2 5-(2-Bromophenyl)-3-phenyl-1-(triuoromethyl)-3,11-
dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole
(3b). Yield 82%; Mp 139–141 ꢀC; IR (KBr): 3068, 2942, 1597,
1482, 1456, 1311, 1233, 1129, 1016, 872, 755 cmꢁ1 1H NMR
;
(300 MHz, CDCl3): d 8.01–7.93 (m, 1H), 7.83 (d, J ¼ 8.3 Hz, 2H),
7.72 (d, J ¼ 7.0 Hz, 1H), 7.44–7.33 (m, 3H), 7.32–7.13 (m, 4H),
7.10–6.93 (m, 2H), 4.30 (s, 1H), 2.98 (dd, J ¼ 13.5, 3.0 Hz, 1H),
2.5 (dd, J ¼ 13.5, 3.0 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d
4.2 General procedure for the synthesis of 1-phenyl-3-
(triuoromethyl)-1H-pyrazol-5(4H)-one 2a
2
151.5, 148.3, 137.5, 137.2, 137.0 (q, JC–F ¼ 38.1 Hz), 135.4,
A mixture of ethyl 4,4,4-triuoro-3-oxobutanoate (5 g, 0.1 mmol) 130.9, 129.0, 128.6, 128.2, 127.6, 127.2, 126.9, 126.2, 122.3, 121.4
1
and phenyl hydrazine (2.9 g, 0.1 mmol) in acetic acid, in a round (q, JC–F ¼ 269.7 Hz), 121.3, 121.0, 116.7, 102.9, 102.0, 30.5,
bottom ask was heated to reux till the completion of the 26.7 ppm; ESI-MS: m/z 513 [M + H]+; HRMS (ESI) anal.
reaction (monitored by TLC). Then the neat reaction mass was calcd for C25H17BrF3N2O2 m/z 513.0420 [M + H]+, found
allowed to come to room temperature, acetic acid was removed 513.0421.
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4.3.3 4-(3-Phenyl-1-(triuoromethyl)-3,11-dihydro-5,11-
RSC Advances
4.3.7 5-(Naphthalen-2-yl)-3-phenyl-1-(triuoromethyl)-
methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazol-5-yl)benzoni- 3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyr-
trile (3c). Yield 58%; Mp 181–184 ꢀC; IR (KBr): 2924, 2853, 2230, azole (3g). Yield 64%; Mp 139–141 ꢀC; IR (KBr): 3049, 2923,
1594, 1481, 1310, 1233, 1130, 1014, 886, 745 cmꢁ1 1H NMR 1596, 1481, 1234, 1134, 1018, 756 cmꢁ1 1H NMR (500 MHz,
; ;
(500 MHz, CDCl3): d 7.87–7.68 (m, 6H), 7.48–7.38 (m, 2H), 7.36– CDCl3): d 8.00–7.78 (m, 6H), 7.75–7.71 (m, 1H), 7.57–7.50 (m,
7.18 (m, 3H), 7.11–6.98 (m, 2H), 4.32 (s, 1H), 2.57 (dd, J ¼ 13.5, 2H), 7.39 (t, J ¼ 7.7 Hz, 2H), 7.33–7.21 (m, 3H), 7.14 (d, J ¼ 7.9
3.0 Hz, 1H), 2.34 (dd, J ¼ 13.5, 2.8 Hz, 1H) ppm; 13C NMR (125 Hz, 1H), 7.02 (t, J ¼ 7.3 Hz, 1H), 4.32 (s, 1H), 2.66 (dd, J ¼ 13.7,
MHz, CDCl3): d 151.4, 148.3, 144.2, 137.3, 137.1 (q, 2JC–F ¼ 38.1 3.0 Hz, 1H), 2.43 (dd, J ¼ 13.7, 2.8 Hz, 1H) ppm; 13C NMR (125
2
Hz), 132.5, 129.2, 128.5, 127.4, 127.0, 126.6, 125.8, 122.6, 121.2 MHz, CDCl3): d 151.9, 149.0, 137.6, 137.1 (q, JC–F ¼ 38.1 Hz),
1
(q, JC–F ¼ 268.8 Hz), 121.1, 118.1, 116.4, 113.5, 102.3, 136.6, 133.5, 132.7, 129.1, 128.5, 128.3, 127.7, 127.6, 127.1,
1
101.6, 34.1, 26.9 ppm; ESI-MS: m/z 460 [M + H]+; HRMS (ESI) 127.0, 126.9, 126.6, 126.2, 125.1, 123.0, 122.3, 121.4 (q, JC–F
¼
anal. calcd for C26H17F3N3O2 m/z 460.1267 [M + H]+, found 269.7 Hz), 121.0, 116.5, 103.2, 101.8, 34.3, 27.2 ppm; ESI-MS:
460.1276.
m/z 485 [M + H]+; HRMS (ESI) anal. calcd for C29H20F3N2O2 m/z
4.3.4 5-(4-Chlorophenyl)-3-phenyl-1-(triuoromethyl)-3,11- 485.1471 [M + H]+, found 485.1474.
dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole
4.3.8 3-(3-Phenyl-1-(triuoromethyl)-3,11-dihydro-5,11-
(3d). Yield 84%; Mp 176–177 ꢀC; IR (KBr): 3172, 2930, 1908, methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazol-5-yl)phenol
1592, 1496, 1235, 1134, 1092, 1011, 755 cmꢁ1 1H NMR (500 (3h). Yield 80%; Mp 172–173 ꢀC; IR (KBr): 3306, 3068,
;
MHz, CDCl3): d 7.79–7.74 (m, 2H), 7.63 (d, J ¼ 8.6 Hz, 2H), 7.47– 2951, 1483, 1453, 1228, 1141, 1111, 1014, 761, 699 cmꢁ1
;
1H
7.39 (m, 4H), 7.33–7.27 (m, 2H), 7.24–7.18 (m, 1H), 7.06 (d, J ¼ NMR (300 MHz, CDCl3): d 7.69 (d, J ¼ 7.5 Hz, 2H), 7.42–7.27 (m,
8.0 Hz, 1H), 7.01 (t, J ¼ 7.4 Hz, 1H), 4.29 (s, 1H), 2.56 (dd, J ¼ 5H), 7.23–7.16 (m, 2H), 7.08–6.9 (m, 4H), 4.24 (s, 1H), 2.23 (d, J ¼
13.7, 3.2 Hz, 1H), 2.34 (dd, J ¼ 13.7, 2.8 Hz, 1H) ppm; 13C NMR 2.6 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3 + DMSO-d6):
(125 MHz, CDCl3): d 151.6, 148.7, 138.1, 137.5, 137.1 (q, 2JC–F
¼
d 157.7, 151.5, 148.6, 140.3, 137.1, 136.6 (q, JC–F ¼ 37.9 Hz),
2
1
38.1 Hz), 135.5, 129.1, 128.8, 128.3, 127.3, 127.2, 127.0, 126.0, 129.2, 128.7, 127.8, 126.8, 126.5, 125.9, 121.7, 121.0 (q, JC–F
¼
1
122.4, 121.3 (q, JC–F ¼ 267.9 Hz), 121.1, 116.4, 102.6, 101.7, 269.0 Hz), 120.7, 116.2, 116.1, 116.0, 112.6, 102.7, 101.4,
34.3, 27.0 ppm; ESI-MS: m/z 469 [M + H]+; HRMS (ESI) anal. 33.9, 26.6 ppm; ESI-MS: m/z 451 [M + H]+; HRMS (ESI)
calcd for C25H17ClF3N2O2 m/z 469.0925 [M + H]+, found anal. calcd for C25H18F3N2O3 m/z 451.1264 [M + H]+, found
469.0929.
4.3.5 3-Phenyl-5-(p-tolyl)-1-(triuoromethyl)-3,11-dihydro-
5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3e). Yield phenyl)-3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino-
451.1268.
4.3.9 3-Phenyl-1-(triuoromethyl)-5-(3,4,5-trimethoxy-
ꢀ
71%; Mp 154–156 ꢀC; IR (KBr): 3066, 3037, 2950, 1597, 1481, [4,5-c]pyrazole (3i). Yield 68%; Mp 154–156 C; IR (KBr): 3037,
1229, 1139, 1107, 1015, 755 cmꢁ1; 1H NMR (300 MHz, CDCl3): d 3004, 2936, 2836, 1512, 1240, 1126, 1011, 844, 756 cmꢁ1 1H
;
7.80 (d, J ¼ 7.5 Hz, 2H), 7.58 (d, J ¼ 8.1 Hz, 2H), 7.41 (t, J ¼ 7.3 NMR (500 MHz, CDCl3): d 7.83 (d, J ¼ 7.7 Hz, 2H), 7.42 (t, J ¼ 7.7
Hz, 2H), 7.33–7.16 (m, 5H), 7.09–6.96 (m, 2H), 4.28 (s, 1H), 2.57 Hz, 2H), 7.33–7.28 (m, 2H), 7.24–7.19 (m, 1H), 7.07 (d, J ¼ 7.7
(dd, J ¼ 13.5, 3.0 Hz, 1H), 2.42 (s, 3H), 2.36 (dd, J ¼ 13.7, 2.8 Hz, Hz, 1H), 7.02 (t, J ¼ 7.4 Hz, 1H), 6.92 (s, 2H), 4.31 (s, 1H), 3.90 (s,
1H) ppm; 13C NMR (125 MHz, CDCl3): d 151.9, 149.1, 139.3, 3H), 3.88 (s, 6H), 2.59 (dd, J ¼ 13.7, 3.2 Hz, 1H), 2.43 (dd, J ¼
2
137.6, 137.1 (q, JC–F ¼ 38.1 Hz), 136.7, 129.2, 129.1, 128.2, 13.7, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d 153.2,
1
2
127.1, 126.9, 126.2, 125.5, 122.1, 121.4 (q, JC–F ¼ 269.7 Hz), 151.7, 148.9, 138.8, 137.5, 137.0 (q, JC–F ¼ 38.1 Hz), 134.9,
1
121.1, 116.5, 103.1, 101.7, 34.5, 27.2, 21.1 ppm; ESI-MS: m/z 449 129.0, 128.3, 127.1, 127.0, 126.0, 122.3, 121.3 (q, JC–F ¼ 268.8
[M + H]+; HRMS (ESI) anal. calcd for C26H20F3N2O2 m/z 449.1471 Hz), 120.9, 116.4, 103.09, 103.02, 101.8, 60.8, 56.1, 34.3, 27.1
[M + H]+, found 449.1469.
ppm; ESI-MS: m/z 525 [M + H]+; HRMS (ESI) anal. calcd for
4.3.6 5-(Benzo[d][1,3]dioxol-5-yl)-3-phenyl-1-(triuoro-
C
28H24F3N2O5 m/z 525.1631 [M + H]+, found 525.1621.
methyl)-3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino-
4.3.10 5-(4-Methoxyphenyl)-3-phenyl-1-(triuoromethyl)-
ꢀ
[4,5-c]pyrazole (3f). Yield 70%; Mp 165–167 C; IR (KBr): 2899, 3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyr-
1
1736, 1598, 1487, 1256, 1134, 1037, 1012, 762 cmꢁ1; H NMR azole (3j). Yield 69%; Mp 159–161 ꢀC; IR (KBr): 3062, 2938, 2843,
(500 MHz, CDCl3): d 7.78 (d, J ¼ 7.6 Hz, 2H), 7.42 (t, J ¼ 7.4 Hz, 1599, 1480, 1311, 1256, 1139, 1109, 1018, 760 cmꢁ1; H NMR
1
2H), 7.31–7.27 (m, 2H), 7.22–7.17 (m, 2H), 7.15 (d, J ¼ 1.6 Hz, (500 MHz, CDCl3): d 7.79 (d, J ¼ 7.6 Hz, 2H), 7.62 (d, J ¼ 8.8 Hz,
1H), 7.05 (d, J ¼ 7.9 Hz, 1H), 7.00 (t, J ¼ 7.4 Hz, 1H), 6.88 (d, J ¼ 2H), 7.41 (t, J ¼ 7.4 Hz, 2H), 7.32–7.27 (m, 2H), 7.22–7.17
8.0 Hz, 1H), 6.03 (s, 2H), 4.27 (s, 1H), 2.55 (dd, J ¼ 13.7, 3.0 Hz, (m, 1H), 7.06 (d, J ¼ 7.9 Hz, 1H), 7.02–6.96 (m, 3H), 4.28 (s, 1H),
1H), 2.34 (dd, J ¼ 13.8, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz, 3.85 (s, 3H), 2.56 (dd, J ¼ 13.7, 3.0 Hz, 1H), 2.36 (dd, J ¼ 13.7, 2.8
CDCl3): d 151.8, 148.9, 148.4, 147.8, 137.5, 137.1 (q, 2JC–F ¼ 38.1 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d 160.3, 151.9, 149.1,
Hz), 133.5, 129.1, 128.2, 127.1, 126.9, 126.1, 122.2, 121.3 (q, 1JC–F 137.6, 137.1 (q, JC–F ¼ 38.1 Hz), 131.7, 130.5, 129.1, 128.2,
2
1
¼ 269.7 Hz), 121.1, 119.5, 116.4, 108.1, 106.5, 103.0, 101.7, 127.0, 126.2, 122.1, 121.4 (q, JC–F ¼ 268.8 Hz), 121.1, 116.5,
101.4, 34.6, 27.2 ppm; ESI-MS: m/z 479 [M + H]+; HRMS (ESI) 113.8, 113.6, 103.1, 101.7, 55.3, 34.5, 27.2 ppm; ESI-MS: m/z 465
anal. calcd for C26H18F3N2O4 m/z 479.1213 [M + H]+, found [M + H]+; HRMS (ESI) anal. calcd for C26H20F3N2O3 m/z 465.1420
479.1216.
[M + H]+, found 465.1420.
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1511, 1482, 1237, 1117, 1014, 754 cmꢁ1
;
1H NMR (300 MHz,
4.3.11 5-(4-(Allyloxy)phenyl)-3-phenyl-1-(triuoromethyl)-
3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyr-
azole (3k). Yield 74%; Mp 145–147 ꢀC; IR (KBr): 3071, 2922,
CDCl3): d 7.74 (d, J ¼ 7.7 Hz, 2H), 7.42 (t, J ¼ 7.3 Hz, 2H), 7.32–
7.19 (m, 2H), 7.16–7.08 (m, 1H), 6.96–6.82 (m, 2H), 4.18 (s, 1H),
2.31 (dd, J ¼ 13.4, 3.2 Hz, 1H), 2.21 (dd, J ¼ 13.4, 3.0 Hz, 1H),
2.15–2.02 (m, 3H), 1.07 (q, J ¼ 6.2, 3.2 Hz, 6H) ppm; 13C NMR
1
2856, 1598, 1484, 1439, 1311, 1227, 1137, 1012, 754 cmꢁ1; H
NMR (300 MHz, CDCl3): d 7.79 (d, J ¼ 8.6 Hz, 2H), 7.45–7.34 (m,
3H), 7.32–7.16 (m, 5H), 7.10–6.96 (m, 3H), 6.12–5.98 (m, 1H),
5.41 (dd, J ¼ 17.1, 1.3 Hz, 1H), 5.29 (dd, J ¼ 10.5, 1.3 Hz, 1H),
4.56 (d, J ¼ 5.0 Hz, 2H), 4.28 (s, 1H), 2.56 (dd, J ¼ 13.7, 3.2 Hz,
1H), 2.35 (dd, J ¼ 13.7, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz,
CDCl3): d 158.6, 151.8, 148.9, 141.0, 137.5, 137.0 (q, 2JC–F ¼ 38.1
Hz), 132.9, 129.6, 129.0, 128.2, 127.1, 126.9, 126.1, 122.2, 121.4
2
(125 MHz, CDCl3): d 151.6, 149.0, 137.6, 137.0 (q, JC–F ¼ 37.9
1
Hz), 128.9, 128.0, 127.0, 126.8, 126.3, 121.7, 121.4 (q, JC–F
¼
269.5 Hz), 121.1, 116.3, 104.4, 101.8, 47.7, 30.8, 26.5, 24.1, 23.8
ppm; ESI-MS: m/z 415 [M + H]+; HRMS (ESI) anal. calcd for
C23H22F3N2O2 m/z 415.1627 [M + H]+, found 415.1627.
4.3.16 9-Chloro-3,5-diphenyl-1-(triuoromethyl)-3,11-dihy-
dro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3p).
Yield 70%; Mp 190–192 ꢀC; IR (KBr): 2927, 1480, 1450, 1401,
1
(q, JC–F ¼ 269.7 Hz), 121.0, 118.1, 117.8, 116.4, 115.4, 112.5,
102.9, 101.7, 68.8, 34.4, 27.1 ppm; ESI-MS: m/z 491 [M + H]+;
HRMS (ESI) anal. calcd for C28H22F3N2O3 m/z 491.1577 [M + H]+,
found 491.1588.
1316, 1279, 1232, 1138, 1011, 855 cmꢁ1 1H NMR (500 MHz,
;
CDCl3): d 7.79 (d, J ¼ 7.5 Hz, 2H), 7.70–7.63 (m, 2H), 7.53–7.38
(m, 5H), 7.33–7.27 (m, 2H), 7.19–7.13 (m, 1H), 7.03–6.97 (m,
1H), 4.25 (s, 1H), 2.58 (dd, J ¼ 13.5, 3.0 Hz, 1H), 2.34 (dd, J ¼
13.5, 3.0 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3 + DMSO-d6): d
4.3.12 3-Phenyl-5-(4-(prop-2-yn-1-yloxy)phenyl)-1-(triuoro-
methyl)-3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino
ꢀ
[4,5-c]pyrazole (3l). Yield 75%; Mp 137–140 C; IR (KBr): 3309,
2
150.0, 148.3, 138.3, 136.8, 136.4 (q, JC–F ¼ 38.5 Hz), 129.0,
3039, 2925, 2122, 1599, 1483, 1444, 1311, 1286, 1138, 1112,
1019, 759 cmꢁ1; 1H NMR (300 MHz, CDCl3): d 7.79 (d, J ¼ 7.7 Hz,
2H), 7.41 (t, J ¼ 7.7 Hz, 3H), 7.37–7.17 (m, 5H), 7.11–6.96 (m,
3H), 4.73 (d, J ¼ 2.4 Hz, 2H), 4.29 (s, 1H), 2.58 (dd, J ¼ 13.5, 3.0
Hz, 1H), 2.49 (t, J ¼ 2.2 Hz, 1H), 2.36 (dd, J ¼ 13.7, 2.8 Hz, 1H)
ppm; 13C NMR (125 MHz, CDCl3): d 157.6, 151.8, 148.8, 141.1,
128.6, 128.0, 127.5, 127.3, 126.8, 126.1, 125.9, 124.9, 120.7 (q,
1JC–F ¼ 269.5 Hz), 120.5, 117.3, 102.6, 100.5, 33.3, 26.3 ppm; ESI-
MS: m/z 469 [M + H]+; HRMS (ESI) anal. calcd for C25H17ClF3-
N2O2 m/z 469.0925 [M + H]+, found 469.0932.
4.3.17 9-Bromo-3,5-diphenyl-1-(triuoromethyl)-3,11-dihy-
dro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3q).
Yield 71%; Mp 192–194 ꢀC; IR (KBr): 2925, 2853, 1478, 1451,
2
137.6 (q, JC–F ¼ 37.3 Hz), 137.5, 129.6, 129.0, 128.2, 127.1,
1
126.9, 126.1, 121.3 (q, JC–F ¼ 267.8 Hz), 122.2, 121.1, 118.8,
1315, 1232, 1140, 1072, 1013, 876 cmꢁ1 1H NMR (500 MHz,
;
116.4, 115.5, 112.8, 102.8, 101.7, 78.1, 75.8, 55.8, 34.3, 27.0 ppm;
ESI-MS: m/z 489 [M + H]+; HRMS (ESI) anal. calcd for
CDCl3): d 7.79 (d, J ¼ 8.3 Hz, 2H), 7.70–7.62 (m, 2H), 7.53–7.37
(m, 6H), 7.35–7.27 (m, 2H), 6.95 (d, J ¼ 8.3 Hz, 1H), 4.25 (s, 1H),
2.58 (dd, J ¼ 13.5, 3.0 Hz, 1H), 2.34 (dd, J ¼ 13.5, 3.0 Hz, 1H)
ppm; 13C NMR (125 MHz, CDCl3): d 151.1, 148.9, 139.0, 137.4,
C
28H20F3N2O3 m/z 489.1420 [M + H]+, found 489.1431.
4.3.13 5-Methyl-3-phenyl-1-(triuoromethyl)-3,11-dihydro-
5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole
(3m).
2
Yield 76%; Mp 148–150 ꢀC; IR (KBr): 2950, 1599, 1482, 1228,
137.1 (q, JC–F ¼ 38.1 Hz), 131.1, 129.5, 129.1, 128.6, 128.2,
1
1
1129, 1072, 1014, 754 cmꢁ1; H NMR (300 MHz, CDCl3): d 7.75
128.0, 127.3, 125.5, 121.3 (q, JC–F ¼ 269.7 Hz), 121.1, 118.3,
114.2, 103.0, 101.0, 34.1, 27.0 ppm; ESI-MS: m/z 513 [M + H]+;
HRMS (ESI) anal. calcd for C25H17BrF3N2O2 m/z 513.0420 [M +
H]+, found 513.0436.
(d, J ¼ 7.5 Hz, 2H), 7.43 (t, J ¼ 7.3 Hz, 2H), 7.34–7.19 (m, 2H),
7.17–7.09 (m, 1H), 6.98–6.84 (m, 2H), 4.2 (s, 1H), 2.37 (dd, J ¼
13.4, 3.2 Hz, 1H), 2.26 (dd, J ¼ 13.5, 3.0 Hz, 1H), 1.96 (s, 3H)
ppm; 13C NMR (125 MHz, CDCl3): d 151.6, 149.1, 137.6, 136.9 (q,
2JC–F ¼ 37.2 Hz), 129.0, 128.0, 127.1, 126.9, 125.9, 121.8, 121.4
4.3.18 9-Methoxy-3,5-diphenyl-1-(triuoromethyl)-3,11-
dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole
(3r). Yield 76%; Mp 162–165 ꢀC; IR (KBr): 2927, 2854, 1493,
1
(q, JC–F ¼ 269.7 Hz), 121.2, 116.3, 102.4, 101.8, 32.2, 26.75,
1451, 1314, 1284, 1213, 1141, 1010, 851 cmꢁ1 1H NMR (500
;
26.72 ppm; ESI-MS: m/z 373 [M + H]+; HRMS (ESI) anal. calcd for
C
20H16F3N2O2 m/z 373.1158 [M + H]+, found 373.1161.
MHz, CDCl3): d 7.80 (d, J ¼ 8.5 Hz, 2H), 7.71–7.66 (m, 2H), 7.50–
7.44 (m, 3H), 7.41 (t, J ¼ 7.6 Hz, 2H), 7.28 (t, J ¼ 7.3 Hz, 1H), 6.99
(d, J ¼ 8.8 Hz, 1H), 6.85–6.82 (m, 1H), 6.77–6.73 (m, 1H), 4.23 (s,
1H), 3.79 (s, 3H), 2.56 (dd, J ¼ 13.7, 3.2 Hz, 1H), 2.35 (dd, J ¼
13.7, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d 154.5,
4.3.14 5-Ethyl-3-phenyl-1-(triuoromethyl)-3,11-dihydro-
5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole
(3n).
Yield 71%; Mp 105–106 ꢀC; IR (KBr): 3066, 2984, 2941, 1597,
1531, 1484, 1399, 1133, 1012, 854, 755 cmꢁ1; 1H NMR (300 MHz,
CDCl3): d 7.75 (d, J ¼ 7.7 Hz, 2H), 7.42 (t, J ¼ 7.5 Hz, 2H), 7.34–
7.19 (m, 2H), 7.16–7.08 (m, 1H), 6.96–6.85 (m, 2H), 4.20 (s, 1H),
2.35–2.16 (m, 4H), 1.18 (t, J ¼ 7.3 Hz, 3H) ppm; 13C NMR (125
2
149.2, 145.7, 139.6, 137.6, 137.0 (q. JC–F ¼ 38.1 Hz), 129.3,
1
129.1, 128.5, 127.1, 126.8, 125.6, 121.4 (q, JC–F ¼ 269.7 Hz),
121.1, 117.1, 113.8, 111.7, 103.2, 101.5, 55.7, 34.4, 27.4 ppm;
ESI-MS: m/z 465 [M + H]+; HRMS (ESI) anal. calcd for
C26H20F3N2O3 m/z 465.1420 [M + H]+, found 465.1424.
2
MHz, CDCl3): d 151.8, 149.1, 137.6, 136.9 (q, JC–F ¼ 38.1 Hz),
1
129.0, 128.0, 127.0, 126.9, 126.2, 121.7, 121.4 (q, JC–F ¼ 268.8
4.3.19 9-Bromo-7-chloro-3,5-diphenyl-1-(triuoromethyl)-
3,11-dihydro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyr-
azole (3s). Yield 70%; Mp 200–204 ꢀC; IR (KBr): 2944, 1595,
Hz), 121.0, 116.2, 104.4, 101.9, 32.6, 30.0, 26.5, 7.7 ppm; ESI-MS:
m/z 387 [M + H]+; HRMS (ESI) anal. calcd for C21H18F3N2O2 m/z
387.1314 [M + H]+, found 387.1320.
1480, 1456, 1316, 1247, 1132, 1031, 1015, 871 cmꢁ1; H NMR
1
4.3.15 5-Isobutyl-3-phenyl-1-(triuoromethyl)-3,11-dihy-
dro-5,11-methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3o).
Yield 70%; Mp 138–139 ꢀC; IR (KBr): 3073, 3027, 2956, 2930,
(500 MHz, CDCl3): d 7.75 (t, J ¼ 7.7 Hz, 4H), 7.53–7.48 (m, 3H),
7.46 (d, J ¼ 2.2 Hz, 1H), 7.42 (t, J ¼ 7.6 Hz, 2H), 7.31 (t, J ¼ 7.4 Hz,
1H), 7.24 (s, 1H), 4.27 (s, 1H), 2.65 (dd, J ¼ 13.8, 3.2 Hz, 1H), 2.27
35014 | RSC Adv., 2014, 4, 35009–35016
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(dd, J ¼ 14.0, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d
M. Presset, Y. Coquerel and J. Rodriguez, Chem. Rev., 2013,
113, 525.
2
148.7, 147.7, 138.4, 137.3, 137.1 (q, JC–F ¼ 38.1 Hz), 131.4,
1
¨
129.6, 129.1, 128.8, 128.6, 127.3, 127.2, 125.8, 121.2 (q, JC–F
¼
2 J. Troger, J. Prakt. Chem., 1887, 36, 225.
´
269.7 Hz), 121.1, 111.0, 103.7, 100.2, 34.1, 27.3 ppm; ESI-MS: m/
z 547 [M + H]+; HRMS (ESI) anal. calcd for C25H16BrClF3N2O2 m/
z 547.0030 [M + H]+, found 547.0053.
3 (a) C. Pardo, E. Sesmilo, E. Gutierrez-Puebla, A. Monge,
J. Elguero and A. Fruchier, J. Org. Chem., 2001, 66, 1607; (b)
M. Harmata and T. Murray, J. Org. Chem., 1989, 54, 3761;
(c) C. J. Wallentin, T. Wixe, O. F. Wendt, K. E. Bergquist
4.3.20 5-Phenyl-1-(triuoromethyl)-3,11-dihydro-5,11-
methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3t). Yield
78%; Mp 89–91 ꢀC; IR (KBr): 3115, 2928, 1598, 1498, 1289, 1236,
1180, 1132, 1017, 754 cmꢁ1; 1H NMR (300 MHz, CDCl3): d 7.75–
7.65 (m, 2H), 7.50–7.39 (m, 3H), 7.24–7.14 (m, 2H), 7.10–6.93
(m, 2H), 4.23 (s, 1H), 2.49 (dd, J ¼ 13.7, 3.2 Hz, 1H), 2.33 (dd, J ¼
13.5, 2.8 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d 153.9,
¨
and K. Warnmark, Chem.–Eur. J., 2010, 16, 3994; (d)
ˇ
ˇ
S. Stoncius, E. Butkus, A. Zilinskas, K. Larsson,
¨
¨
¨
L. Ohrstrom, U. Berg and K. Warnmark, J. Org. Chem.,
2004, 69, 5196.
4 K. Naemura, R. Fukunaga, M. Komatsu, M. Yamanaka and
H. Chikamatsu, Bull. Chem. Soc. Jpn., 1989, 62, 83.
5 (a) E. B. Veale, D. O. Frimannsson, M. Lawler and
T. Gunnlaugsson, Org. Lett., 2009, 11, 4040; (b) E. B. Veale
and T. Gunnlaugsson, J. Org. Chem., 2010, 75, 5513; (c)
Q. Xin, X. T. Tao, F. Z. Wang, J. L. Sun, D. C. Zou,
F. J. Wang, H. J. Liu, Z. Liu, Y. Ren and M. H. Jiang, Org.
Electron., 2008, 9, 1076.
6 I. Manolov, C. Maichle-Moessmer and E. Niquet, Z.
Naturforsch., B: J. Chem. Sci., 2006, 61, 207.
7 (a) D. U. Chen, P. Y. Kuo and D. Y. Yang, Bioorg. Med. Chem.
Lett., 2005, 15, 2665; (b) I. Manolov and N. D. Danche, Eur. J.
Med. Chem., 1995, 30, 531.
2
152.1, 139.7, 133.2 (q, JC–F ¼ 37.2 Hz), 129.1, 128.3, 128.2,
1
126.8, 126.0, 125.7, 121.9, 120.6 (q, JC–F ¼ 269.5 Hz), 116.5,
102.3, 101.9, 34.6, 26.8 ppm; ESI-MS: m/z 359 [M + H]+; HRMS
(ESI) anal. calcd for C19H14F3N2O2 m/z 359.1001 [M + H]+, found
359.1015.
4.3.21 5-(p-Tolyl)-1-(triuoromethyl)-3,11-dihydro-5,11-
methanobenzo[7,8][1,3]dioxocino[4,5-c]pyrazole (3u). Yield
73%; Mp 88–89 ꢀC; IR (KBr): 3119, 2925, 1599, 1498, 1235, 1180,
1134, 1109, 1017, 753 cmꢁ1; 1H NMR (500 MHz, CDCl3): d 11.75
(s, 1H), 7.55 (d, J ¼ 8.0 Hz, 2H), 7.25–7.13 (m, 4H), 7.01 (d, J ¼ 8.0
Hz, 1H), 6.94 (t, J ¼ 7.3 Hz, 1H), 4.19 (s, 1H), 2.43 (dd, J ¼ 13.7,
3.0 Hz, 1H), 2.38 (s, 3H), 2.30 (dd, J ¼ 13.7, 2.8 Hz, 1H) ppm;
13C NMR (125 MHz, CDCl3): d 153.9, 152.1, 138.9, 136.9,
8 K. Weinges and H. Theobald, Justus Liebigs Ann. Chem., 1971,
743, 203.
9 S. H. Mashraqui, M. B. Patil, H. D. Mistry, S. Ghadigaonkar
and A. Meetsma, Chem. Lett., 2004, 33, 1058.
¨
2
133.3 (q, JC–F ¼ 37.9 Hz), 128.9, 128.1, 126.8, 126.0, 125.6,
1
121.8, 120.6 (q, JC–F ¼ 269.0 Hz), 116.5, 102.1, 102.0,
34.5, 26.8, 21.0 ppm; ESI-MS: m/z 373 [M + H]+; HRMS (ESI) 10 (a) A. B. Pomilio, O. Muller, G. Schilling and K. Weinges,
anal. calcd for C20H16F3N2O2 m/z 373.1158 [M + H]+, found
Justus Liebigs Ann. Chem., 1977, 597; (b) C. Selenski and
T. R. R. Pettus, Tetrahedron, 2006, 62, 5298.
373.1175.
4.3.22 3-(5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3- 11 G. Yin, T. Ren, Y. Rao, Y. Zhou, Z. Li, W. Shu and A. Wu, J.
(2-hydroxyphenyl)-1-phenylpropan-1-one (4). Yield 59%; Mp Org. Chem., 2013, 78, 3132.
166–168 ꢀC; IR (KBr): 3400, 3063, 2924, 1682, 1598, 1406, 1368, 12 F. Wang, F. Chen, M. Qu, T. Li, Y. Liu and M. Shi, Chem.
1311, 1101, 752, 689 cmꢁ1; 1H NMR (500 MHz, CDCl3): d 10.96
Commun., 2013, 49, 3360.
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Acknowledgements
We are grateful to SERB-DST New Delhi for nancial support
(grant no. SB/EMEQ-075/2013). BCJ is thankful to UGC, New
Delhi for JRF.
Notes and references
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