Clean synthesis of N-pyrrolyl azoles by metal-free oxidative cross-coupling using recyclable hypervalent iodine reagent

Article abstract of DOI:10.1248/cpb.c15-00469

The facile and clean oxidative coupling reaction of pyrroles with azoles has been achieved using the recyclable hypervalent iodine(III) reagents having adamantane structures. These iodine(III) reagents could be recovered from the reaction mixtures by a simple solid-liquid separation, i.e., filtration, for reuse.

Full text of DOI:10.1248/cpb.c15-00469

Vol. 63, No. 10
Chem. Pharm. Bull. 63, 819–824 (2015)
819
Regular Article
Clean Synthesis of N-Pyrrolyl Azoles by Metal-Free Oxidative Cross-
Coupling Using Recyclable Hypervalent Iodine Reagent
Koji Morimoto, Ryosuke Ogawa, Daichi Koseki, Yusuke Takahashi, Toshifumi Dohi, and
,†
Yasuyuki Kita*
College of Pharmaceutical Sciences, Ritsumeikan University; 1–1–1 Nojihigashi, Kusatsu, Shiga 525–8577, Japan.
Received June 7, 2015; accepted June 29, 2015
The facile and clean oxidative coupling reaction of pyrroles with azoles has been achieved using the re-
cyclable hypervalent iodine(III) reagents having adamantane structures. These iodine(III) reagents could be
recovered from the reaction mixtures by a simple solid–liquid separation, i.e., filtration, for reuse.
Key words oxidative coupling; hypervalent iodine reagent; recycle; pyrrole; azole; C–N bond formation
The N-pyrrolyl azoles are important fragments in the recent studies have demonstrated the utility of the recyclable
molecules of biological systems or in many pharmaceuticals, hypervalent iodine reagents.38–40)
insecticides, and functional materials, especially, fluorescent
dyes.1–4) In spite of this interest, the preparations of N-aryl
Results and Discussion
azoles are severely restricted because the nitrogen heteroaro-
The use of recyclable hypervalent iodine reagents in reac-
matics are sometimes not a good substrate to use in the tra- tions should be a further promising and ecological approach
ditional arylation methods such as the Ullmann coupling,5–11) for enhancing the practicability of the methods and for re-
since the pyrrole-based metal and halide compounds are ducing the coproduction of stoichiometric amounts of iodo-
sometimes unstable. Katritzky et al. reported the synthesis arenes as a result of the easy removal of the reagents from
of pyrrolyl-benzotriazoles by the Mannich condensation of the reaction mixtures and their reuse.41–59) Therefore, various
o-phthalaldehyde and 2,5-dimethoxy-2,5-dihydrofuran with types of recyclable hypervalent iodine reagents have been
primary amines,12) but this method was not effective for pyr- reported. First, the polymer-supported hypervalent iodine
roles, and the desired products were produced only in less reagents, such as poly(diacetoxyiodo)styrene (PDAIS) and
than 10% yields. As a new approach, the oxidative C–H bond poly[bis(trifluoroacetoxyiodo)]styrene (PBTIS), incorporat-
functionalization strategies of pyrroles13–22) might be expected ing phenyliodine(III) diacetate (PIDA) and phenyliodine(III)
to be an attractive methodology for enabling rapid access to bis(trifluoroacetate) (PIFA) in their polymer backbones were
these molecules. Recently, we have developed a new hyper- developed.41–48) Inspired by this study, other chemists have
valent iodine-induced oxidative coupling of pyrroles at the also reported new recyclable hypervalent iodine compounds
N1-positions of the azoles.23) In 2014, Chen and colleagues having fluorous tags49–52) and ionic supports.53–55)
reported the oxidative coupling method of 1,2,3-triazoles with
We have previously developed a structurally new recyclable
pyrroles using N-iodosuccinimide (NIS) as an oxidant, in hypervalent iodine reagent 1a, namely, 1,3,5,7-tetrakis[4-
which the reactions preferentially occurred at the N2-position (diacetoxyiodo)phenyl]adamantane (Fig. 1), having a very
of the 1,2,3-triazoles.24) However, these methods produced similar reactivity to that of PIDA, which was easily recovered
stoichiometric quantities of iodoarene or succinimide as a by precipitation utilizing the insolubility of the tetraiodide
waste product after the reaction (Chart 1).
2, stoichiometrically produced from 1a after the reactions,
Hypervalent iodine reagents have received much attention in common polar solvents.56–59) Our recyclable hypervalent
due to their mild oxidation abilities and low toxicity, easy iodine(III) reagents 1 having an adamantane core have several
handling, as alternatives to toxic heavy metal reagents.25–32) advantages over the conventional polymer-supported reagents
For developing a new coupling for heteroaromatic compounds, in reactivity and recyclability; they typically show higher
we have been engaged in the study of the oxidative C–H bond reactivities compared to the polymer-supported reagents and
arylations using hypervalent iodine reagents that utilize the no degradation of their backbones after repeated use, which
new reactivities of the heteroaromatic iodonium intermedi- are derived from the well-defined tetrahedral structures.
ates.33–37) As mentioned, we developed a hypervalent iodine- Considering the background of the recyclable iodine reagent,
induced oxidative coupling of pyrroles at the N1-positions of we improved our coupling reaction conditions by using the
the azoles.23) This new method is versatile in allowing the recyclable iodine reagent and avoided the generation of a
reactions under metal-free and mild conditions, and tolerates stoichiometric amount of iodobenzene waste from our initial
a diverse series of functionalities of the pyrroles and azole conditions.
coupling partners. We envisioned that a recycling version of
Based on our initial studies, we thus attempted the cross-
this oxidative coupling should become feasible and provide an coupling reaction of N-benzylpyrrole 3a with triazole 4a using
eco-friendly synthetic method (Chart 2) because a number of the recyclable reagent 1a based on the standard reaction con-
ditions in Cl(CH2)2Cl (DCE) in combination with bromotri-
† Present address: Research Organization of Science and Technology, Ritsu-
methylsilane (TMSBr) at 70°C, yielding the cross-product
5aa in 74% yield (Chart 3, Eq. 1). Other adamantane-based
meikan University; 1–1–1 Nojihigashi, Kusatsu, Shiga 525–8577, Japan.
*To whom correspondence should be addressed. e-mail: kita@ph.ritsumei.ac.jp
© 2015 The Pharmaceutical Society of Japan

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Chem. Pharm. Bull.
Vol. 63, No. 10 (2015)
Chart 1. Reported Metal-Free Oxidative Cross-Coupling Reactions of Pyrroles with Azoles
Chart 2. C–N Coupling Reaction of Triazoles with Pyrroles Using Recyclable Hypervalent Iodine Reagent
the tetraiodide 2. A series of recycling processes was finally
completed by reoxidation of the recovered tetraiodide 2 to the
initial reagents 1a using m-chloroperbenzoic acid (mCPBA).
In this way, the reagents could be reproduced with almost the
same purity and have been repeatedly used without any loss of
activities.58,59) Indeed, the reuse of the reagent 1a in the same
reaction showed a comparable result in terms of the product
yield and recovery of the tetraiodide 2.
With the reagent 1a (1×1/4eq, 100mol% of iodine(III) atom
relative to the substrates), the reactions of the pyrroles 3 with
azoles 4 smoothly proceeded under the homogeneous condi-
tions in the presence of TMSBr in DCE (Chart 4). This meth-
od revealed a tolerance toward the N-protecting groups (see
substrates 3b, c and d), and in most cases, good yields were
obtained. In the case of the N-free pyrrole 3e, the coupling
reaction efficiently proceeded and the corresponding coupling
Fig. 1. Recyclable Hypervalent Iodine(III) Reagents Having Adaman-
tane Cores
recyclable iodine(III) reagents 1b and c (Fig. 1) were less ef- product 5ea was obtained in 62% yield. 2-Ethyl pyrrole 3f
fective for the coupling reaction of N-benzylpyrrole 3a with gave the desired coupling product 5fa in a significant yield.
triazole 4a than the recyclable reagent 1a. In addition, the When we attempted the coupling reaction of the poly-substi-
less reactive polymer-supported reagent, the commercially tuted pyrroles, 3g, h and i, the coupling products, 5ga, ha and
available PDAIS, gave no coupling product 5aa under the ia, were obtained in moderate yield, respectively. When the
given condition. As a result, the recyclable iodine(III) reagent reaction was performed using 3-methylindole 3j, the reaction
1a and TMSBr in DCE at 70°C gave the best result. The proceeded and gave the coupling product 5ja in 70% yield.
use of a highly polar, but low nucleophilic solvent, such as
Encouraged by these results, we applied this reaction to
1,1,1,3,3,3-hexafluoroisopropanol (HFIP, (CF3)2CHOH), trifluo- other azoles to synthesize various 2-(azol-1-yl)pyrrole and
roethanol (TFE), or other Lewis acids, such as BF3·Et2O and indole derivatives (Chart 5). The reactions of pyrroles 3a
trimethylsilyl trifluoromethane sulfonate (TMSOTf) in DCE, and e with different azoles 4b–e smoothly proceeded and the
resulted in no production of the desired coupling product.
coupling products 5ab–ee were produced in good to excellent
The oxidants 1a could be easily separated from the reaction yields. The 4-butyl-1,2,3-triazole 4b also afforded the desired
mixtures as the corresponding reduced forms, i.e., the tetraio- coupling adduct 5ab in 76% yield (Eq. 1). The reaction of N-
dide 2 by a simple solid–liquid separation. The procedure to benzylpyrrole 3a with pyrazole 4c and imidazole 4d smoothly
recover the tetraiodide started with the removal of the solvent proceeded to give 5ac and ad in good yields (Eq. 2). The
under reduced pressure by a rotary evaporator. Methanol was N-free pyrrole 3e coupled with benzotriazole 4e afforded the
then added to the resulting oily residues to precipitate the tet- coupling product 5ee in 69% yield (Eq. 3).
raiodide 2. As the tetraiodides are hardly soluble in methanol,
they were simultaneously precipitated as a white powder by
Conclusion
adding methanol and were collected by filtration to recover
We have demonstrated the facile and clean method for the

Vol. 63, No. 10 (2015)
Chem. Pharm. Bull.
821
Chart 3. Oxidative Cross-Coupling Reaction of Pyrrole 3a with Triazole 4a Using Recyclable Hypervalent Iodine(III) Reagents 1
Reaction conditions: (a) Pyrroles 3 (0.4mmol), 1,2,3-triazole 4a (1.2mmol), TMSBr (0.8mmol), and iodine reagent 1a (0.4×1/4mmol) in DCE (4mL) at 70°C for 3h. (b)
Yields are those for the isolated N1-selective coupling products. (c) Reaction performed at room temperature. Boc=tert-butoxycarbonyl.
Chart 4. Scope of Reactions(a, b)
oxidative C–N cross-coupling reaction of pyrroles and azoles
using recyclable hypervalent iodine reagents. The present pro-
Experimental
General Remarks The 1H- and 13C-NMR spectra were
tocol provided easy and less waste access to N-functionalized recorded by a JEOL JMN-400 spectrometer operating at
azoles. The advantageous features of this coupling method are 400MHz in chloroform-d3 (CDCl3) at 25°C with tetra-
a metal-free procedure and mild reaction conditions. Further methylsilane as the internal standard. Data are reported as
studies are underway to extend this coupling to other types of follows: chemical shift in ppm (δ), integration, multiplicity
substrates.
(s=singlet, d=doublet, t=triplet, q=quartet, brs=broad sin-

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Vol. 63, No. 10 (2015)
Reaction conditions: Pyrroles 3 (0.4mmol), azoles 4 (1.2mmol), TMSBr (0.8mmol), and iodine reagent 1a (0.4×1/4mmol) in DCE (4mL) at 70°C for 3h.
Chart 5. Cross-Coupling Reaction of Different Azoles with Pyrrole
glet, m=multiplet), coupling constant (Hz). The infrared spec- (SiO2, hexane) to give 1-(1-benzyl-1H-pyrrol-2-yl)-1H-1,2,3-
tra (IR) were obtained using a Hitachi 270-50 spectrometer, triazole 5aa (57mg, 74%).
absorptions are reported in reciprocal centimeters. The mass
1-(1-Benzyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole (5aa) 1H-NMR
spectra were obtained using a Shimadzu GCMS-QP 5000 (400MHz, CDCl3) δ: 5.01 (2H, s), 6.27 (1H, t, J=4.0Hz),
instrument with ionization voltages of 70eV. The high resolu- 6.32–6.34 (1H, m), 6.80 (1H, t, J=4.0Hz), 6.93–6.95 (2H, m),
tion mass spectra were performed by the Elemental Analysis 7.23–7.27 (3H, m), 7.46 (1H, s), 7.70 (1H, s) ppm; 13C-NMR
Section of Osaka University. Column chromatography and (100MHz, CDCl3) δ: 50.4, 105.7, 107.5, 121.9, 124.8, 126.8,
TLC were carried out on Merck Silica gel 60 (230–400 mesh) 126.9, 127.7, 128.6, 133.1, 136.6ppm; IR (KBr) ν 3126, 2927,
and Merck Silica gel F254 plates (0.25mm), respectively. 1709, 1573, 1497, 1323, 1068, 1013, 783, 719, 616cm−1; MS
The spots and bands were detected by UV irradiation (254, matrix assisted laser desorption/ionization-time of flight
365 nm).
(MALDI-TOF) Calcd for C13H13N4 m/z 225.11 [M+H]+, Found
Preparation of a Recyclable Hypervalent Iodine Reagent 224.2 (39), 225.2 (100).
1a To a stirred solution of 1,3,5,7-tetrakis(4-iodophenyl)-
1-(1-Methyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole (5ba) 1H-NMR
adamantane 2 (1.42g, 1.5mmol) in dichloromethane (150mL)– (400MHz, CDCl3) δ: 3.49 (3H, s), 6.18 (1H, t, J=3.4Hz),
acetic acid (150mL) was added mCPBA (ca. 69% purity, 6.24–6.26 (1H, m), 6.67 (1H, t, J=3.4Hz), 7.73 (1H, s), 7.80
3.12g, 18mmol) at room temperature. The mixture was stirred (1H, s) ppm; 13C-NMR (100MHz, CDCl3) δ: 33.5, 104.8, 107.1,
for 12h under the same reaction conditions during which 122.1, 125.1, 126.5, 133.2ppm; IR (KBr) ν 3125, 2950, 1574,
the cloudy solution became clear. The resultant mixture was 1503, 1321, 1270, 1230, 1091, 1035, 1034, 787, 722, 611cm−1;
filtered, and dichloromethane was removed using a rotary MS (MALDI-TOF) Calcd for C7H9N4 m/z 149.08 [M+H]+,
evaporator. Hexane was added to the residue to precipitate the Found: 148.1 (24), 149.2 (100).
1,3,5,7-tetrakis[4-(diacetoxyiodo)phenyl]adamantane 1a. After
filtration, the almost pure product was obtained in nearly ylate (5ca) 1H-NMR (400MHz, CDCl3) δ: 1.32 (9H, s), 6.26
quantitative yield.
tert-Butyl 2-(1H-1,2,3-Triazol-1-yl)-1H-pyrrole-1-carbox-
(1H, t, J=3.4Hz), 6.41–6.42 (1H, m), 7.36 (1H, t, J=3.4Hz),
General Procedure for the Oxidative C–N Coupling Re- 7.74 (1H, s), 7.76 (1H, s) ppm; 13C-NMR (100MHz, CDCl3) δ:
action of Azoles with Pyrroles Using a Recyclable Iodine 27.3, 84.9, 109.2, 112.4, 121.8, 124.0, 127.4, 132.5, 147.1ppm;
Reagent 1a (Charts 3–5) To a stirred solution of N-benzyl- IR (KBr) ν 3127, 2982, 1749, 1597, 1433, 1317, 1149, 957, 843,
pyrrole 3a (46mg, 0.30mmol) in DCE (3mL) was added recy- 736cm−1; MS (MALDI-TOF) Calcd for C11H14N4O2 m/z 234.11
clable reagent 1a (106.2mg, 0.30×1/4mmol). TMSBr (92mg, [M]+, Found 234.3 (100), 235.3 (14).
0.6mmol) and 1,2,3-triazole 4a (51mg, 0.9mmol) were then
1-(1-Phenyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole (5da)
A
1
added at room temperature. The reaction mixture was stirred brown solid; mp 105–107°C; H-NMR (400MHz, CD2Cl2) δ:
at 70°C for 3h, then dichloromethane and saturated sodium 6.40 (1H, t J=3.4Hz), 6.52–6.54 (1H, m), 7.00–7.01 (1H, m),
hydrogen carbonate aqueous were successively added with 7.06–7.08 (2H, m), 7.29–7.32 (3H, m), 7.57 (1H, d, J=1.0Hz),
stirring. The organic layer was then separated and evaporated 7.64 (1H, d, J=1.0Hz) ppm; 13C-NMR (100MHz, CDCl3)
to dryness. Methanol was added to the reaction mixture, and δ: 107.8, 108.4, 122.3, 124.6, 126.9, 127.8, 129.4, 133.3,
1H-NMR 137.4ppm; IR (KBr) ν 3125, 1596, 1477, 1457, 1354, 1260,
it was filtered to give the tetraiodide 2 (confirmed by
analysis and TLC), which was washed several times with 1237, 1038, 935, 765cm−1; high resolution (HR)-MS (FAB)
small portion of methanol (MeOH) for purification. The fil- Calcd for C12H11N4 m/z 211.0984 [M+H]+, Found 211.0978.
trate was evaporated and subjected to column chromatography
1-(1H-Pyrrol-2-yl)-1H-1,2,3-triazole
(5ea) 1H-NMR

Vol. 63, No. 10 (2015)
Chem. Pharm. Bull.
823
(400MHz, CDCl3) δ: 6.24–6.25 (2H, m), 6.77–6.78 (1H, 107.0, 120.4, 127.0, 127.5, 128.5, 129.0, 132.7, 137.5, 141.1ppm;
m), 7.78 (1H, s), 7.86 (1H, s), 9.26 (1H, brs) ppm; 13C-NMR IR (KBr) ν 3107, 3063, 2930, 1577, 1496, 1487, 1455, 1281,
(100MHz, CDCl3) δ: 98.1, 108.8, 116.9, 121.9, 126.0, 1251, 1112, 1068, 996, 756, 714cm−1; HR-MS (FAB) Calcd for
133.9ppm; IR (KBr) ν 3151, 1589, 1499, 1299, 1050, 1028, 912, C14H14N3 m/z 224.1188 [M+H]+, Found 224.1182.
743 cm−1; MS (MALDI-TOF) Calcd for C6H7N4 m/z 135.07;
[M+H]+, Found: 133.9 (84), 134.9 (100).
1-(1-Benzyl-1H-pyrrol-2-yl)-1H-imidazole (5ad) 1H-NMR
(400MHz, CDCl3) δ: 4.79 (2H, s), 6.19–6.20 (2H, m), 6.71
1-(5-Ethyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole (5fa) 1H-NMR (1H, t, J=2.4Hz), 6.82 (1H, s), 6.87–6.90 (2H, m), 7.06 (1H,
(400MHz, CDCl3) δ: 1.25 (3H, t, J=7.2Hz), 2.65 (2H, q, s), 7.20–7.29 (3H, m), 7.37 (1H, s) ppm; 13C-NMR (100MHz,
J=7.2Hz), 5.91 (1H, s), 6.12 (1H, t, J=3.0Hz), 7.73 (1H, s), 7.81 CDCl3) δ: 49.5, 105.7, 107.3, 120.8, 121.7, 125.2, 126.3, 127.8,
(1H, s), 9.30 (1H, brs) ppm; 13C-NMR (100MHz, CDCl3) δ: 128.7, 129.2, 137.0, 139.1ppm; IR (KBr) ν 3110, 2924, 1708,
13.4, 20.7, 98.0, 104.6, 121.6, 124.4, 133.5, 133.7ppm; IR (KBr) 1574, 1490, 1348, 1311, 1235, 1060, 819, 720, 660cm−1;
ν 3152, 2969, 1601, 1597, 1223, 1050, 1018, 776cm−1; MS HR-MS (FAB) Calcd for C14H14N3 m/z 224.1188 [M+H]+,
(MALDI-TOF) Calcd for C8H11N4 m/z 163.10 [M+H]+, Found Found 224.1182.
162.18 (92), 163.19 (100).
1-(1H-Pyrrol-2-yl)-1H-benzo[d][1,2,3]triazole (5ee)
A
1-(4-Ethyl-3,5-dimethyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole white solid; mp 110–113°C; 1H-NMR (400MHz, CDCl3)
(5ga) 1H-NMR (400MHz, CDCl3) δ: 1.07 (3H, t J=7.6Hz), δ: 6.36–6.38 (1H, m), 6.44–6.48 (1H, m), 6.86–6.88 (1H,
2.01 (3H, s), 2.19 (3H, s), 2.41 (2H, q, J=1.7Hz), 7.75–7.77 (2H, m), 7.42 (1H, t, J=8.0Hz), 7.56 (1H, t, J=8.0Hz), 7.73 (1H,
m), 8.37 (1H, brs) ppm; 13C-NMR (100MHz, CDCl3) δ: 8.7, d, J=8.3Hz), 8.09 (1H, d, J=8.3Hz), 9.17 (1H, brs) ppm;
10.8, 15.5, 17.5, 109.4, 119.7, 121.2, 122.0, 123.7, 133.4ppm; IR 13C-NMR (100MHz, CDCl3) δ: 99.4, 109.0, 110.5, 116.8,
(KBr) ν 3195, 2961, 1619, 1542, 1450, 1384, 1284, 1035, 913, 120.0, 124.6, 124.9, 128.5, 131.9, 145.6ppm; IR (KBr) ν 3202,
782cm−1; MS (MALDI-TOF) Calcd for C10H15N4 m/z 191.13 2571, 1714, 1583, 1442, 1216, 1085, 1027, 938, 744, 658cm−1;
[M+H]+, Found 190.15 (64), 191.16 (100).
HR-MS (FAB) Calcd for C10H9N4 m/z 185.0826 [M+H]+,
1-(3,5-Dimethyl-1H-pyrrol-2-yl)-1H-1,2,3-triazole (5ha) Found 185.0822.
1H-NMR (400MHz, CDCl3) δ: 2.06 (3H, s), 2.25 (3H, s),
5.77 (1H, d, J=2.9Hz), 7.765 (1H, s), 7.77 (1H, s), 8.56 (1H,
Acknowledgments This work was partially supported by
brs) ppm; 13C-NMR (100MHz, CDCl3) δ: 10.5, 12.8, 108.42, Grants-in-Aid for Scientific Research (A) from the Japan So-
108.44, 110.3, 123.6, 126.4, 133.4ppm; IR (KBr) ν 3148, 2925, ciety for the Promotion of Science (JSPS), a Grant-in-Aid for
1618, 1538, 1326, 1224, 1094, 953, 793cm−1; MS (MALDI- Scientific Research on Innovative Areas “Advanced Molecular
TOF) Calcd for C8H11N4 m/z 163.10 [M+H]+, Found 162.13 Transformation by Organocatalysts” from the Ministry of
(56), 163.14 (100).
1-(1H-1,2,3-Triazole-1-yl)-4,5,6,7-tetrahydro-2H-isoin- of Japan. K. M. also acknowledges support from the Grant-in-
dole (5ia)
white solid; mp 127–129°C; 1H-NMR Aid for Young Scientists (B) from the JSPS.
Education, Culture, Sports, Science and Technology (MEXT)
A
(400MHz, CDCl3) δ: 1.70–1.81 (4H, m), 2.58–2.61 (4H, m),
6.47 (1H, d, J=2.5Hz), 7.77 (1H, s), 7.81 (1H, s), 8.86 (1H, brs)
Conflict of Interest The authors declare no conflict of
ppm; 13C-NMR (100MHz, CDCl3) δ: 21.5, 22.0, 23.3, 23.4, interest.
109.6, 111.6, 120.6, 121.8, 133.7ppm; IR (KBr) ν 3148, 2925,
1714, 1533, 1325, 1230, 1034, 767, 592cm−1; MS (MALDI-
References and Notes
TOF) Calcd for C10H13N4 m/z 189.11 [M+H]+, Found 188.05
(40), 189.06 (100).
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1-(1-Benzyl-1H-pyrrol-2-yl)-4-butyl-1H-1,2,3-triazole
(5ab) A brown solid; mp 73–77°C; 1H-NMR (400MHz,
CDCl3) δ: 0.95 (3H, t, J=7.6Hz), 1.31–1.41 (2H, m), 1.59–1.67
(2H, m), 2.71 (2H, t, J=7.8Hz), 5.01 (2H, s), 6.25 (1H, t,
J=3.7Hz), 6.29–6.31 (1H, m), 6.78–6.79 (1H, m), 6.94–6.97
(2H, m), 7.15 (1H, s), 7.24–7.29 (3H, m) ppm; 13C-NMR
(100MHz, CDCl3) δ: 13.8, 22.1, 25.0, 31.3, 50.4, 105.4, 107.3,
121.6, 123.9, 125.3, 126.9, 127.7, 128.6, 136.8, 147.6ppm; IR
(KBr) ν 3111, 2956, 2859, 1950, 1576, 1496, 1453, 1274, 1230,
1274, 1070, 1007, 913, 722cm−1; MS (MALDI-TOF) Calcd for
C17H21N4 m/z 281.18 [M+H]+, Found 281.13 (100), 282.13 (20).
1-(1-Benzyl-1H-pyrrol-2-yl)-1H-pyrazole (5ac) 1H-NMR
(400MHz, CDCl3) δ: 4.96 (2H, s), 6.16 (1H, t, J=3.4Hz),
6.19–6.21 (1H, m), 6.28 (1H, s), 6.64 (1H, s), 6.95 (2H, d,
J=8.3Hz), 7.18–7.23 (3H, m), 7.36 (1H, d, J=2.4Hz), 7.69 (1H,
s) ppm; 13C-NMR (100MHz, CDCl3) δ: 50.0, 104.4, 106.1,
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