Air-stable zirconocene bis(perfluorobutanesulfonate) as a highly efficient catalyst for synthesis of N-heterocyclic compounds

Article abstract of DOI:10.1016/j.jorganchem.2015.02.014

Zirconocene bis(perfluorobutanesulfonate) is air- and water-stable and proved to be ionic on basis of conductivity measurements. It exhibits high catalytic efficiency for the synthesis of N-heterocyclic compounds under solvent-free condition, such as benzimidazoles, benzodiazepines, dihydropyrimidinones and dihydropyridines under mild condition. Furthermore, it can be reused without loss of activity in a test of five cycles. This catalytic system affords a simple and efficient approach for the synthesis of N-heterocyclic compounds.

Full text of DOI:10.1016/j.jorganchem.2015.02.014

Accepted Manuscript
Air-stable zirconocene bis(perfluorobutanesulfonate) as a highly efficient catalyst for
synthesis of N-heterocyclic compounds
Jinying Wang, Ningbo Li, Renhua Qiu, Xiaohong Zhang, Xinhua Xu, Shuang-Feng
Yin
PII:
S0022-328X(15)00082-0
10.1016/j.jorganchem.2015.02.014
JOM 18914
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 2 December 2014
Revised Date: 21 January 2015
Accepted Date: 10 February 2015
Please cite this article as: J. Wang, N. Li, R. Qiu, X. Zhang, X. Xu, S.-F. Yin, Air-stable zirconocene
bis(perfluorobutanesulfonate) as a highly efficient catalyst for synthesis of N-heterocyclic compounds,
Journal of Organometallic Chemistry (2015), doi: 10.1016/j.jorganchem.2015.02.014.
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Air-stable zirconocene bis(perfluorobutanesulfonate)
as a highly efficient catalyst for synthesis of
N-heterocyclic compounds
Jinying Wang,† Ningbo Li,† Renhua Qiu,*a Xiaohong Zhang,a Xinhua Xu*a,b and
a
a
Shuang-Feng Yin*a
aCollege of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai, University, Tianjing 300071, China
†
These authors contributed equally to this work.
Fax: (+ 86) 731-88821546 E-mail: renhuaqiu@hnu.edu.cn; xhx1581@hnu.edu; sf_yin@hnu.edu.cn

ACCEPTED MANUSCRIPT
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com
Air-stable zirconocene bis(perfluorobutanesulfonate) as a highly efficient catalyst for synthesis of N-
heterocyclic compounds
Jinying Wang,†a Ningbo Li,†a Renhua Qiu,*a Xiaohong Zhang a, Xinhua Xu*a,b and Shuang-Feng Yin*a
aCollege of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai, University, Tianjing, 300071, China
†
These authors contributed equally to this work.
Fax: (+ 86) 731-88821546; E-mail: renhuaqiu@hnu.edu.cn; xhx1581@hnu.edu.cn; sf_yin@hnu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Zirconocene bis(perfluorobutanesulfonate) is air- and water-stable and proved to be
ionic on basis of conductivity measurements. It exhibits high catalytic efficiency for the
synthesis of N-heterocyclic compounds under solvent-free condition, such as
benzimidazoles, benzodiazepines, dihydropyrimidinones and dihydropyridines under
mild condition. Furthermore, it can be reused without loss of activity in a test of five
cycles. This catalytic system affords a simple and efficient approach for the synthesis of
N-heterocyclic compounds.
Available online
Keywords:
Zirconocene
Perfluorobutanesulfonate
N-heterocyclic compounds
2015 Elsevier Ltd. All rights reserved
.
1. Introduction
long reaction time, various side products, unsatisfactory yields,
and complicated procedure. During the last decade, rare earth
metal triflates (Sc, Y, Yb) have been found as unique Lewis
acids. They are water tolerant, and can effectively promote
above reactions to obtain these N-heterocyclic compounds in
good yield [16]. Unfortunately, due to the high price of
scandium and ytterbium salts and their intolerance towards
various functional groups, Sc(OTf)3 and Yb(OTf)3 are limited in
application. Thus, developing an air-stable, highly efficient and
recyclable catalyst for the synthesis of these N-heterocyclic
compounds is still highly desirable.
N-heterocyclic compounds, such as benzimidazoles,
benzodiazepines, dihydropyrimidinones, and dihydropyridines,
are very useful intermediates or subunits for the development of
molecules of pharmaceutical or biological interest [1]. As
shown in Fig. 1, the drugs containing N-heterocyclic-framework,
such as bilastine, nevitapine, nifedipine, nicardipine and others
have been found to be useful as inhibitors, calcium channel
blockers, anticonvulsant, anti-inflammatory, analgesic,
antihypertensive, and antidepressive agents [2].
In recent years, cationic group metallocene compounds as
Lewis acids have attracted much attention [17]. For example,
Bosnich and Collins groups synthesized the metallocene
bis(triflate)s complexes of titanium and zirconium Cp2M(OTf)2
(Cp = C5H5; M=Ti, Zr), which were successfully employed to
catalyze carbon-carbon bond-forming reactions [18, 19].
Unfortunately, these complexes were not stable in air and
underwent facile hydrolysis. Later, Otera and co-worker found
that the longer perfluoroctanesulfonate groups could be used as
effective counter anions to provide air-stable and water-tolerant
organometallic species in sharp contrast to the corresponding
hygroscopic organometallic triflates [20]. With this in mind, we
have synthesized
a
series of air-stable metallocene
bis(perfluorooctanesulfonate)s complexes Cp2M(OPf)2 (M=Ti,
Zr; Pf = OSO2C8F17), which showed moderate to high catalytic
efficiency in C-C and C-O bond formation reactions [21].
However, their relatively low solubility in organic solvents
owing to the strongly lipophobic nature of C8F17 group maybe
Fig. 1
Due to their good pharmacological activities and wide
application, the synthesis of these compounds has received
much attention for the discovery of improved protocols towards
milder and high yielding approaches [3]. A variety of Lewis
acids catalysts, such as BF3·OEt2 [4], ZrCl4 [5], BiCl3 [6], InBr3
[7], InCl3 [8], I2 [9], FeCl3 [10], TMSCl [11], LiClO4 [12],
Bi(OTf)2 [13], Cu(OTf)2 [14] and others [15], have been applied
for synthesis of these N-heterocyclic compounds. However,
many of these processes suffer major or minor limitations, such
as low yield, poor selectivity, using of organic solvents,
applications of expensive reagents, drastic reaction conditions,
decline
the
catalytic
efficiency
[22].
Besides,
perfluoroctanesulfonate compounds (PFOS) will result in huge
environment pollution and the potential toxicity to animals and
human beings [23]. Hence, we envisioned that introduction of
perfluorobutane anions with relatively weak lipophobic
property maybe increase the solubility as well as the catalytic
efficiency. Also perflurobutanesulfonate compounds (PFBS) are
less terrible and their toxicities to humans and animals were

2
Journal of Organometallic Chemistry
lower than that of PFOS. Based on this idea aAndCasCpEarPt oTf EouDr MAeNffiUcieSntCpRrotIoPcoTls for the synthesis of bisbenzimidazoles have been
ongoing efforts devoted to metallocene complexes, we have
developed.
prepared
zirconocene
bis(perfluorobutanesulfonate)s
2.2 Synthesis of 1,5-benzodiazepines
[Cp2Zr(H2O)2]+[OSO2C4F9]-2 (1a) and examined its catalytic
efficiency towards for synthesis of N-heterocyclic compounds,
Next, we assessed 1a as a catalyst for preparation of 1,5-
benzodiazepines. The reactions were carried out by taking a 1:2
mole ratio of o-phenylenediamine and ketones along with a
catalytic amount of 1a (2 mol%) under solvent-free conditions. The
reaction proceeds very well at room temperature giving good-to-
excellent yields of 1,5-benzodiazepines derivatives (6). As can be
seen in Table 2, different aliphatic ketones reacted with o-
phenylenediamine affording 6b, 6c, 6e with 90%, 88%, 87% yields,
respectively. Cyclohexanone also exhibits good reactivity in this
such
as
benzimidazoles,
benzodiazepines,
dihydropyrimidinones and dihydropyridines.
2. Results and discussion
In previous study, we have demonstrated that the complex 1a
has the nature of air-stability, water tolerance, thermally-
stability and strong Lewis-acidity. In this paper, we also
investaged its conductivity, which shows that the molar
conductivity (Λ) of 1a is 142 µScm-1 in CH3CN (1.0 mmol L-1)
Table 2 Preparation of 1,5-benzodiazepines catalyzed by 1a a
o
at 25 C. The large molar conductivity value is consistent with
complete ionization into 1:2 electrolyte in CH3CN, implying
that the complex is cationic in solution. Accordingly, the
empirical formula of the complex can be written as
[Cp2Zr(H2O)2]+[OSO2C4F9]-2 (1a). Above features of complex
1a encourage us to evaluate its performances as Lewis acid
catalyst for the synthesis of N-heterocyclic compounds.
2.1 Synthesis of 1,2-disubstitued benzimidazoles
Using 1a as catalyst, o-phenylenediamine can react with the
aldehydes for synthesis of 1, 2-disubstitued benzimidazoles at room
temperature under solvent-free conditions, and good-to-excellent
product yields were obtained. As shown in Table 1.
Table 1 Preparation of 1,2-disubstitued
catalyzed by 1a a
benzimidazoles
ao-phenylenediamine (2a) (1.0 mmol), ketones (2.5 mmol), catalyst
(0.02 mmol). Solvent-free; temp: r.t; 6a-6c: 15 min; 6d-6e: 20 min;
6f-6g: 30 min; the isolated yields.
Table 3 Synthesis of dihydropyrimidinones catalyzed by 1a a
N
N
N
N
N
OMe
OMe
CH3
N
CH3
4a, 90%
4b, 91%
4c, 92%
N
N
N
N
N
N
N
Br
Cl
Cl
N
Br
4f, 85%
4d, 89%
4e, 86%
N
N
O
N
N
N
N
O
4i, 75%
4g, 80%
4h, 82%
a
o-phenylenediamine (2a) (1.0 mmol), aromatic aldehydes (2.0
mmol), catalyst 1a (0.02 mmol). Solvent-free; Temp: r.t; 30 min. the
isolated yields.
Aromatic aldehydes with electron-donating and electron-
withdrawing groups were employed (4a-4i). Despite variation of
reaction rate, the yields were high. The aromatic aldehydes with
electron-donating groups (e.g., CH3, OCH3 and N(CH3)2) exhibit
higher reactivity than those in the para-position of the phenyl plane
with electron-withdrawing groups (e.g., Cl, Br). Gratifyingly, 2-
furfural and 2-naphthaldehyde show high reactivity with 80% and
82% yield, respectively (4g, 4h). In addition, the alkyl aldehyde (n-
butanal) also shows good reactivity with 75% yield (4i). Thus,
a
Aromatic aldehydes (1.0 mmol), 1,3-dicarbonyl compound (1.0
mmol), urea (1.2 mmol); catalyst 1a (0.05 mmol); Solvent-free;
temp: 100 C; 9a-9e, 9i-9k: 1.5 h; 9f-9g: 2 h; 9h: 3 h; 9l: 6 h; the
o
isolated yields.

ACCEPTED MAaNldUehySdCes RcIaPnTreact
catalytic system with o-phenylenediamine in the yield of 86% (6d).
In addition, acetophenone and o-methoxyacetophenone also show
good reactivity with 85% and 81% yield, respectively (6f, 6g).
with ethyl(methyl) acetylacetate and
ammonium acetate for synthesis of dihydropyridines in a one-pot
condensation at 80 C under solvent- free conditions for 2-3 h, and
o
good-to-excellent product yields were obtained. A wide range of
aromatic aldehydes were subjected to prove the general
applicability of our present procedure. As shown in Table 4, several
sensitive functionalities such as -OH, OMe, halogen (Cl, Br) are
unaffected under the present reaction conditions. The electron-
withdrawing groups attached in the phenyl ring of the aldehydes
have lower efficiency than that of electron-donating groups (11b-
11g). The cinnamaldehyde with double bond is tolerated in current
catalytic system (11i). For furfural, it still gives the corresponding
product in 91% yield (11j). In addition, the methyl acetoacetate
also shows good reactivity with benzaldehyde (o-nitrobenzaldehyde)
and ammonium acetate, and the yields were 92% and 88%,
respectively (11k, 11l). Furthermore, we investigated the scaled-up
procedure of the product 11h, which is key intermediate for
important cardiovascular drug. As shown in scheme 1, although the
substrate is expanding to ten times, the yield is still up to 90%.
2.3 Synthesis of dihydropyrimidinones
Generally, dihydropyrimidinones was obtained by the three-
component Biginelli reaction. Several efficient Lewis acid catalysts
have been reported in these reactions [14,16]. In most cases, weak
acidity and sensitive to air or moisture remained to be surmounted.
We hence addressed these problems with 1a as catalyst and
achieved the high catalytic efficient way for the Biginelli reaction
in a one-pot condensation under solvent-free conditions for 1.5-6 h.
As shown in Table 3, various aromatic aldehydes were screened
with ethyl acetyl acetate and urea in this catalytic system, and
good-to-excellent yields were obtained (9a-9k). The electron-
withdrawing groups attached in the phenyl ring of the aldehydes
have lower efficiency than that of electron-donating groups (9b-
9g). The cinnamaldehyde with double bond is tolerated in current
catalytic system (9h). The pentane-2,4-dione also has good
reactivity in current catalytic system with benzaldehyde
( substituent benzaldehydes) and urea in the yield of 92%, 90% and
91%, respectively (9i, 9j, 9k). In addition, the alkyl aldehyde
(propionaldehyde) also shows good reactivity with 82% yield (9l).
Table 4 Synthesis of 1,4-dihydropyridines catalyzed by 1a a
Scheme 1 The scaled-up procedure of 11h
2.5 Cycles of catalyst 1a
Table 5 Synthesis of above N-heterocyclic compounds catalyzed
by recovered 1a
Yield
Cycle (%)e
Eq 1a
Yield
(%)e
Yield
(%)e
Yield
(%)e
Cat
Cat
Cat
Cat
(%)f
(%)f
(%)f
(%)f
Eq 2b
Eq 3c
Eq 4d
1
2
3
4
5
92
93
93
92
92
93
94
93
92
93
91
91
90
91
92
92
91
91
92
93
94
95
95
93
94
95
95
96
94
94
93
93
94
92
93
94
94
94
93
93
[a] 2a (1.0 mmol); 3a (2.0 mmol); cat. 1a (0.02 mmol); RT; 30 min. [b] 2a (1.0
mmol); 5a (2.5 mmol); cat. 1a (0.02 mmol); RT; 15 min. [c] 3a (1.0 mmol); 7a
(1.0 mmol); 8a (1.2 mmol); cat. 1a (0.05 mmol); 100 oC; 1.5 h. [d] 3a (1.0
mmol); 7a (2.0 mmol); 10a (1.2 mmol); cat. 1a (0.05 mmol); 80 oC; 2 h. [e]
Isolated yield of desired product. [f] Isolated yield of recovered catalyst
a
Aromatic aldehydes (1.0 mmol), 1,3-dicarbonyl compound (2.0
mmol), ammonium acetate (1.2 mmol); catalyst 1a (0.05 mmol);
Solvent-free; temp: 80 oC; 11a-11c: 2 h; 11d-11g: 2.5 h; 11i-11j: 3
h; 11k-11l: 2 h; the isolated yields.
To test the reusability of the catalyst and the reproducibility of
catalytic performance, 1a was subjected to recycling experiments
of above reactions (eq 1: 2a + 3a → 4a; eq 2: 2a + 5a → 6a; eq 3:
3a + 7a + 8a → 9a; eq 4: 3a + 7a + 10a → 11a) (Table 5). The
detected change in product yield was minimal in a trial of five
2.4 Synthesis of 1,4-dihydropyridines
Similarly, 1,4-dihydropyridines were obtained by four-
component Hantzsch reaction. Using 1a as an catalyst, the aromatic

4
Journal of Organometallic Chemistry
cycles, demonstrating that the catalyst is stable and suitable for
reuse.
the reaction. The combined CH2Cl2 solution was removed by
evaporation in vacuum and was then subjected to silica gel column
chromatograph with ethyl acetate-n-hexane (2:8) as eluent to afford
pure compound.
ACCEPTED MANUSCRIPT
2.6 Catalyst comparison investigation
Compound 4a:[13b] White solid, Mp: 130-131 C; H NMR (400
MHz, CDCl3) δ: 7.88 (d, J = 8.0 Hz, 1H), 7.70-7.68 (m, 2H), 7.49-
7.45 (m, 3H), 7.35-7.30 (m, 4H), 7.25-7.22 (m, 2H), 7.11(d, J = 8.0
Hz, 2H), 5.47 (s, 2H); EI-MS (m/z): 284.1 (M+).
o
1
The
catalytic
activities
of
Cp2ZrCl2,
together
1a,
with
[Cp2Zr(H2O)3][OSO2CF3]2·THF
(12)[18]
[Cp2Zr(H2O)3][OSO2C8F17]2·THF (13)[21] were assessed for above
reactions (eq 1: 2a + 3a → 4a; eq 2: 2a + 5a → 6a; eq 3: 3a + 7a
+ 8a→ 9a; eq 4: 3a + 7a + 10a→ 11a) (Scheme in Table 5). All
reactions were carried out in the presence of above catalysts, and
the yields of the respective are compiled in Table 6. High yields
were attained over 1a, while the other catalysts showed much lower
yields, plausibly due to their lower Lewis acidity or moisture-
sensitive features, such as Cp2ZrCl2 and the complex 12. To our
surprise, the complex 13 only shows moderate catalytic efficiency
in the above these reactions compared with 1a. We speculated that
the relatively lower catalytic efficiency of complex 13 may be
owing to the strongly lipophobic property of the perfluorooctyl
group because the perfluoro anions well wrapping the cationic
metal center make the lipophilic substrates hard to approach the
center metal atom for activating. Furthermore, after being stored in
air for three months, the complex 1a also exhibited catalytic
efficiency comparable to the freshly prepared sample.
o
Compound 4b:[13b] White solid, Mp: 129-130 C; 1H NMR (400
MHz, CDCl3) δ: 7.83 (d, J = 7.6 Hz, 1H), 7.64-7.62 (m, 2H), 7.31-
7.27 (m, 1H), 7.22-7.20 (m, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.97-
6.95 (m, 2H), 6.86-6.84 (m, 2H), 5.37 (s, 2H), 3.84 (s, 3H), 3.78 (s,
3H); 13C NMR (100 MHz, CDCl3) δ: 160.83, 159.04, 154.04,
143.06, 136.00, 130.62, 128.40, 127.14, 122.67, 122.45, 122.35,
119.61, 114.35, 114.12, 110.35, 55.30, 55.22, 47.81; EI-MS (m/z):
344.1 (M+).
o
Compound 4c:[13b] White solid, Mp: 128-129 C; 1H NMR (400
MHz, CDCl3) δ: 7.86 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H),
7.30-7.26 (m, 1H), 7.25-7.22 (m, 2H), 7.20-7.17 (m, 2H), 7.11 (d, J
= 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 5.39 (s, 2H), 2.39 (s, 3H),
2.32 (s, 3H); EI-MS (m/z): 312.2 (M+).
o
1
Compound 4d:[13b] Yellow solid, Mp: 165-166 C; H NMR (400
MHz, CDCl3) δ: 7.81 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H),
7.27-7.23 (m, 1H), 7.21-7.17 (m, 2H), 7.02 (d, J = 8.4 Hz, 2H),
6.73 (d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 5.37 (s, 2H), 3.00
(s, 6H), 2.92 (s, 6H); EI-MS (m/z): 370.2 (M+).
Table 6 Catalyst comparison for synthesis of above N-
heterocyclic compounds
Entry
Eq. 1-4
Catalyste
1a
Cp2ZrCl2
12
72
75
80
79
13
81
83
85
84
1a
2b
3c
4d
38
26
19
15
90 (91)f
91 (90)f
94 (93)f
93 (93)f
o
1
Compound 4e:[13b] White solid, Mp: 137-138 C; H NMR (400
MHz, CDCl3) δ: 7.86 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H),
7.43 (d, J = 8.8 Hz, 2H), 7.35-7.24 (m, 4H), 7.18 (d, J = 7.6 Hz,
1H), 7.01 (d, J = 8.4 Hz, 2H), 5.38 (s, 2H); EI-MS (m/z): 352.1
(M+).
2a+3a→4a
2a+5a →6a
3a+7a+8a→9a
3a+7a+10a→11a
[a] 2a (1.0 mmol); 3a (2.0 mmol); cat. (0.02 mmol); RT; 30 min; [b] 2a (1.0
mmol); 5a (2.5 mmol); cat. (0.02 mmol); RT; 15 min; [c] 3a (1.0 mmol); 7a (1.0
mmol); 8a (1.2 mmol); cat. (0.05 mmol); 100 C; 1.5 h; [d] 3a (1.0 mmol); 7a
o
Compound 4f:[13b] White solid, Mp: 159-160 C; 1H NMR (400
o
o
(2.0 mmol); 10a (1.2 mmol); cat. (0.05 mmol); 80 C; 2 h; [e] Isolated yield of
MHz, CDCl3) δ: 7.87 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H),
7.52 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 7.4
Hz, 1H), 7.27 (t, J = 6.6 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 6.96 (d,
J = 8.4 Hz, 2H), 5.38 (s, 2H); EI-MS (m/z): 442.0 (M+).
desired product; [f] Catalyst kept in open air for three months.
3. Experimental Section
Compound 4g:[13b] White solid, Mp: 88-89 oC; 1H NMR (400 MHz,
CDCl3) δ: 7.79-7.77 (m, 1H), 7.64 (s, 1H), 7.51-7.49 (m, 1H), 7.33
(s, 1H), 7.32-7.29 (m, 2H), 7.22 (d, J = 3.6 Hz, 1H), 6.62-6.61 (m,
1H), 6.29-6.28 (m, 1H), 6.24-6.23 (m, 1H), 5.64 (s, 2H); EI-MS
(m/z): 264.2 (M+).
3.1 General
All chemicals were purchased from Aldrich. Co. Ltd and used
as received unless otherwise indicated. The preparation of catalyst
was carried out under nitrogen atmosphere with freshly distilled
solvents unless otherwise noted. Diethyl ether and toluene were
distilled from sodium/benzophenone. The NMR spectra were
recorded at 25 oC on INOVA-400M (USA) calibrated with
tetramethylsilane (TMS) as an internal reference.
o
Compound 4h:[13b] White solid, Mp: 124-126 C; 1H NMR (400
MHz, CDCl3) δ: 8.20 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.91-7.83
(m, 5H), 7.75-7.70 (m, 2H), 7.57-7.46 (m, 5H), 7.37-7.23 (m, 4H),
5.66 (s, 2H); 13C NMR (100 MHz, CDCl3) δ: 154.30, 143.35,
136.39, 133.99, 133.75, 133.45, 132.93, 132.89, 129.30, 129.15,
128.63, 127.94 127.80, 127.28, 126.74, 126,65, 126.31, 126.14,
124.80, 123.91, 123.27, 122.88, 120.08, 110.59, 48.84; EI-MS
(m/z): 384.2 (M+).
3.2 Synthesis of complex 1a
To a solution of Cp2ZrCl2 (292 mg, 1 mmol) in Et2O (20 mL)
was added a solution of AgOSO2C4F9 (854 mg, 2.1 mmol) in Et2O
(10 mL). The mixture was stirred in the dark at room temperature
for 1 h, and filtered. Evaporation furnished a residue, which was
diluted with Et2O (4 mL) and toluene (10 mL). The solution was
kept standing in a refrigerator at -10 oC for 24 h. Colorless crystals
were obtained (642 mg, 75%). M.p. 101-103 C; H NMR (400
MHz, CD3CN) δ = 6.53 (s, 10H, Cp), 3.88 (br.s, H2O); 13C NMR
(100MHz, CD3CN) δ: 115.90; 19F NMR (376 MHz, CD3CN): δ = -
81.70 (s, 3F, CF3-), -115.36 (s, 2F,-CF2-), -122.15--122.18 (m, 2F,-
CF2-), -126.52 to -126.59 (m, 2F,-CF2-).
o
1
Compound 4i:[15c] White solid; Mp: 128-129 C; H NMR (400
MHz, CDCl3) δ: 6.71-6.67 (m, 2H), 6.64-6.61 (m, 2H), 3.23-3.17
(m, 2H), 2.99-2.94 (m, 1H), 1.70-1.64 (m, 1H), 1.60-1.53 (m, 1H),
1.49-1.35 (m, 5H), 0.93 (t, J = 7.4 Hz, 6H); 13C NMR (100MHz,
CDCl3) δ: 140.39, 138.89, 120.70, 120.56, 119.61, 119.08, 58.91,
49.31, 44.70, 33.94, 20.04, 19.01, 14.19, 11.94.
o
1
3.3 Typical procedure for preparation of 1,5-benzodiazepines
catalyzed by 1a
A mixture of o-phenylenediamine (1 mmol) and ketones (2.5
mmol) was well stirred with 1a (0.02 mmol) at r.t. for 15-30 min.
After completion of the reaction, CH2Cl2 (3 × 10 ml) was added to
the reaction mixture and the catalyst was filtered for the next cycle
of the reaction. The combined CH2Cl2 solution was removed by
evaporation in vacuum and was then subjected to silica gel column
chromatograph with ethyl acetate-n-hexane (2:8) as eluent to afford
3.2 Typical procedure for preparation of 1,2-disubstitued
benzimidazoles catalyzed by 1a
A mixture of o-phenylenediamine (1 mmol) and aldehyde (2.0
mmol) was well stirred with 1a (0.02 mmol) at r.t. for 30 min. After
completion of the reaction, CH2Cl2 (3 × 10 mL) was added to the
reaction mixture and the catalyst was filtered for the next cycle of

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1
pure compound.
Compound 9b:[7a]
ACCEPTED MANUSCRIPT White solid, Mp: 199-201 C; H NMR (400
Compound 6a:[15b] Yellow solid, Mp: 138-139 C; H NMR (400
MHz, CDCl3) δ: 7.15-7.13 (m, 1H), 7.00-6.98 (m, 2H), 6.75-6.73
(m, 1H), 2.99 (s, 1H), 2.38 (s, 3H), 2.24 (s, 2H), 1.35 (s, 6H); 13C
NMR (100 MHz, CDCl3) δ: 172.63, 140.48, 137.89, 126.79,
125.59, 122.10, 121.72, 68.37, 45.11, 30.91, 30.48, 29.80; EI-MS
(m/z): 188.2 (M+).
MHz, CDCl3) δ: 8.16 (s, 1H), 7.26-7.22 (m, 2H), 6.84-6.82 (m, 2H)
, 5.75 (s, 1H), 5.34 (d, J = 2.4 Hz, 1H), 4.08-4.04 (m, 2H), 3.78 (s,
3H), 2.33 (s, 3H), 1.17 (t, J = 7.0 Hz, 3H). EI-MS (m/z): 290.1
(M+).
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1
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Compound 9c:[7b] White solid, Mp: 189-191 C; H NMR (400
MHz, d6-DMSO) δ: 9.36 (s, 1H), 9.13 (s, 1H), 7.64 (s, 1H), 7.04 (d,
J = 7.6 Hz, 2H), 7.69 (d, J = 7.6 Hz, 2H), 5.05 (s, 1H), 4.04-3.97
(m, 2H), 2.24 (s, 3H), 1.10 (t, J = 6.4 Hz, 3H); 13C NMR (100MHz,
d6-DMSO) δ: 165.88, 157.01, 152.65, 148.24, 135.89, 127.87,
115.44, 100.17, 59.57, 53.88, 18.20, 14.56; EI-MS (m/z): 276.1
(M+).
Compound 6b:[15b] Pale yellow solid, Mp: 137-138 C; H NMR
(400 MHz, CDCl3) δ: 7.23-7.18 (m, 1H), 6.96 (t, J = 7.4 Hz, 1H),
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1
6.90
-6.84 (m, 1H), 6.68 (d, J = 8.0 Hz, 1H), 3.55 (s, 1H), 2.66
-2.58
(m, 1H), 2.31 (s, 3H), 1.65
-
1.40 (m, 2H), 1.22 (s, 2H), 1.10 (s, 1H),
1.05 (d, J = 7.2 Hz, 2H), 1.02-0.98 (m, 2H), 0.91 (t, J = 7.4 Hz, 2H);
EI-MS (m/z): 216.2 (M+)
Compound 9d:[7b] White solid, 214-216 C; H NMR (400 MHz,
CDCl3) δ: 8.04 (s, 1H), 7.26-7.10 (m, 4H), 5.68 (s, 1H), 5.37 (d, J =
2.4 Hz, 1H), 4.10-4.07 (m, 2H), 2.33 (s, 3H), 2.32 (s, 3H), 1.17 (t, J
= 7.2 Hz, 3H). EI-MS (m/z): 274.2 (M+).
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Compound 6c:[15b] Pale yellow solid, Mp: 119-121 C; H NMR
(400 MHz, CDCl3) δ: 7.16-7.13 (m, 1H), 6.97-6.95 (m, 2H), 6.70-
6.68 (m, 1H), 3.10 (s, 1H), 2.46 (d, J = 7.2 Hz, 2H), 2.24-2.13 (m,
3H),1.76-1.71 (m, 1H), 1.58-1.47 (m, 2H), 1.33 (s, 3H), 1.02-0.96
(m, 12H); EI-MS (m/z): 272.2 (M+)
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Compound 9e:[7a] White solid, Mp: 228-230 C; 1H NMR (400
o
MHz, CDCl3) δ: 7.59 (s, 1H), 7.18 (d, J = 7.2 Hz, 2H), 6.65 (d, J =
8.8 Hz, 2H), 5.44 (s, 1H), 5.30 (d, J = 2.4 Hz, 1H), 4.11-4.05 (m, 2
H), 2.93 (s, 6H), 2.33 (s, 3H), 1.19 (t, J = 7.2 Hz, 3H). EI-MS
(m/z): 303.1 (M+).
Compound 6d:[15b] Yellow solid, Mp: 138-139 C; 1H NMR (400
o
MHz, CDCl3) δ: 7.28 (d, J = 9.2 Hz, 1H), 7.02-6.98 (m, 1H), 6.97-
6.93 (m, 1H), 6.72 (d, J = 7.6 Hz, 1H), 3.81 (br s, 1H), 2.61 (t, J =
6.6 Hz, 2H), 2.40-2.32 (m, 1H), 1.87-1.78 (m, 6H) 1.70-1.67 (m,
3H), 1.60-1.54 (m, 3H), 1.45-1.20 (m, 4H); EI-MS (m/z): 268.2
(M+)
Compound 6e: Yellow solid, Mp: 136-137 C; ATR-FTIR (cm-1):
3340, 2957, 2923, 2853, 1683, 1637, 1596, 1467, 1416, 1376, 1300,
Compound 9f:[7a] White solid, Mp: 211-213 oC; 1H NMR (400
MHz, CDCl3) δ: 8.07 (s, 1H), 7.29-7.24 (m, 4H), 5.85 (s, 1H), 5.37
(d, J = 2.8 Hz, 1H), 4.11-4.06 (m, 2H), 2.33 (s, 3H), 1.17 (t, J = 7.2
Hz, 3H). EI-MS (m/z): 294.1 (M+).
o
Compound 9g:[7a] White solid, Mp: 198-200 oC; H NMR (400
1
1
1255, 1178, 1153, 1107, 978, 931, 845, 750, 722; H NMR (400
MHz, CDCl3) δ: 7.62 (s, 1H), 7.43 (d, J = 7.6 Hz, 2H), 7.20 (d, J =
7.6 Hz, 2H), 5.64 (s, 1H), 5.37 (d, J = 2.8 Hz, 1H), 4.11-4.06 (m,
2H), 2.35 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H). EI-MS (m/z): 340.0
(M+1)+.
Compound 9h: [7a] Pale yellow solid, Mp: 232-235 C; H NMR
(400 MHz, d6-DMSO) δ: 9.21 (s, 1H), 7.61 (s, 1H), 7.45 (d, J = 7.6
Hz, 2H), 7.36 (t, J = 7.4 Hz, 2H), 7.28 (t, J = 7.2 Hz, 1H), 6.41 (d, J
= 16.0 Hz, 1H), 6.25 (dd, J = 15.6 Hz, 6.0 Hz, 1H), 4.80-4.77 (m,
1H), 4.19-4.09 (m, 2H), 2.26 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H); 13C
NMR (100MHz, d6-DMSO) δ: 165.66, 153.08, 149.02, 136.69,
130.41, 129.14, 128.57, 128.05, 126.80, 98.23, 59.69, 52.36, 18.23,
14.72; EI-MS (m/z): 286.1 (M+).
MHz, CDCl3) δ: 7.14-7.12 (m, 1H), 6.97-6.95 (m, 2H), 6.72-6.70
(m, 1H), 3.07 (s, 1H), 2.55 (t, J = 7.8 Hz, 2H), 2.24-2.12 (m, 2H),
1.73-1.66 (m, 2H), 1.62-1.50 (m, 2H), 1.30-1.27 (m, 25H), 0.90-
0.87 (m, 6H); 13C NMR (100MHz, CDCl3) δ: 175.43, 140.96,
137.91, 127.01, 125.37, 121.86, 121.79, 70.89, 43.41, 42.92, 42.44,
31.89, 31.87, 30.13, 29.58, 29.56, 29.51, 29.28, 27.56, 26.56, 24.26,
22.70, 22.68, 14.13; EI-MS (m/z): 384.4 (M+); HRMS Calcd for
C26H44N2: 384.3504; Found: 384.3501.
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1
Compound 6f:[15b] Yellow solid, Mp: 151-152 C; 1H NMR (400
o
MHz, CDCl3) δ: 7.59 (t, J = 7.2 Hz, 4H), 7.34-7.16 (m, 7H), 7.10-
7.02 (m, 2H), 6.84 (d, J = 7.2 Hz, 1H), 3.52 (s, 1H), 3.14 (d, J =
13.2 Hz, 1H), 2.97 (d, J = 13.2 Hz, 1H), 1.76 (s, 3H); EI-MS (m/z):
312.1 (M+).
Compound 6g:[15b] Yellow solid, Mp: 174-176 C; H NMR (400
MHz, CDCl3) δ: 7.41 (d, J = 7.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H),
7.18 (t, J = 7.8 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.04 (t, J = 7.6 Hz,
1H), 6.87-6.82 (m, 3H), 6.78 (d, J = 8.0 Hz, 1H), 6.65 (t, J = 7.4 Hz,
1H), 6.51-6.44 (m, 2H), 4.28 (s, 1H), 4.05 (d, J = 12.8 Hz, 1H),
3.84 (s, 3H), 3.34 (s, 3H), 2.89 (d, J = 13.2 Hz, 1H), 1.69 (s, 3H);
EI-MS (m/z): 372.3(M+).
Compound 9i:[7a] White solid, Mp: 234-236 oC; 1H NMR (400
MHz, d6-DMSO): 9.20 (s, 1H), 7.84 (s, 1H), 7.32 (d, J = 6.8 Hz,
2H), 7.26 (d, J = 6.0 Hz, 3H), 5.27 (s, 1H), 2.30 (s, 3H), 2.11 (s,
3H); 13C NMR (100MHz, d6-DMSO) δ: 194.79, 152.62, 148.64,
144.68, 129.00, 127.83, 126.88, 110.06, 54.25, 30.79, 19.38; EI-
MS (m/z): 230.1 (M+).
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Compound 9j:[15d] White solid, Mp: 240-242 C; H NMR (400
MHz, CDCl3) δ: 7.94 (s, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.18 (d, J =
8.4 Hz, 2H), 5.89 (s, 1H), 5.44 (d, J = 2.8 Hz, 1H), 2.35 (s, 3H),
2.17 (s, 3H); EI-MS (m/z): 309.1 (M+).
3.5 Typical procedure for preparation of dihydropyrimidinones
catalyzed by 1a
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Compound 9k:[15e] White solid, Mp: 201-203 C; H NMR (400
MHz, d6-DMSO): 9.80 (s, 1H), 9.14 (s, 1H), 7.24 (s, 1H), 7.09 (t,
1H, J = 7.4 Hz), 6.99 (d, J = 7.2 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H),
To a stirred solution of aldehyde (1.0 mmol) and 1,3-diketone
compounds (1.0 mmol), urea (1.5 mmol) and catalyst 1a (0.05
mmol) were added and heated at 100 C, until the reaction was
6.75 (t, J = 7.4 Hz, 1H), 5.56 (s, 1H), 2.28 (s, 3H), 2.04 (s, 3H); 13
C
o
NMR (100MHz, d6-DMSO) δ: 195.33, 154.63, 152.69, 148.55,
130.12, 129.04, 127.52, 119.65, 115.97, 108.50, 49.13, 30.04,
19.12; EI-MS (m/z): 246.1 (M+).
Compound 9l:[7a] White solid, Mp: 174-175 oC; H NMR (400
MHz, CDCl3) δ: 7.79 (s, 1H), 5.68 (s, 1H), 4.30-4.26 (m, 1H), 4.22-
4.13 (m, 2H), 2.29 (s, 3H), 1.61-1.55 (m, 2H), 1.28 (t, J = 7.2 Hz,
3H), 0.92 (t, J = 7.4 Hz, 3H); EI-MS (m/z): 212.2 (M+).
completed as indicated by TLC. After completion of the reaction,
CH2Cl2 (3 × 10 ml) was added to the reaction mixture and the
catalyst was filtered for the next cycle of the reaction. The
combined CH2Cl2 solution was removed by evaporation in vacuum
and was then subjected to silica gel column chromatograph with
ethyl acetate-n-hexane (1:2) as eluent to afford pure compound.
1
Compound 9a:[7a] White solid, Mp: 201-203 oC; H NMR (400
1
3.6 Typical procedure for preparation of 1,4-dihydropyridines
MHz, CDCl3) δ: 7.72 (s, 1H), 7.33-7.26 (m, 5H), 5.58 (s, 1H), 5.41
(d, J = 2.4 Hz, 1H), 4.11-4.06 (m, 2H), 2.36 (s, 3H), 1.18-1.15 (t, J
= 7.0 Hz, 3H); 13C NMR (100MHz, CDCl3) δ: 165.62, 153.49,
146.36, 143.68, 128.67, 127.92, 126.57, 101.27, 59.99, 55.66,
18.60, 14.11; EI-MS (m/z): 260.0 (M+).
catalyzed by 1a
To a stirred solution of aldehyde (1.0 mmol) and 1,3-diketone
compounds (2.0 mmol), ammonium acetate (1.2 mmol) and catalyst
o
1a (0.05 mmol) were added and heated at 80 C, until the reaction

6
Journal of Organometallic Chemistry
Compound 11l:[24c] Pale yellow solid, Mp: 172-174 C ; H NMR
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1
was completed as indicated by TLC. After cAomCpleCtioEnPoTf EthDe MANUSCRIPT
reaction, CH2Cl2 (3 × 10 ml) was added to the reaction mixture and
the catalyst was filtered for the next cycle of the reaction. The
combined CH2Cl2 solution was removed by evaporation in vacuum
and was then subjected to silica gel column chromatograph with
ethyl acetate–n-hexane (1:4) as eluent to afford pure compound.
(400 MHz, CDCl3) δ: 7.67 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.6 Hz,
1H), 7.47 (t, J = 7.6 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 6.42 (s, 1H),
5.73 (s, 1H), 3.59 (s, 6H), 2.32 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ: 167.75, 147.77, 145.41, 142.25, 132.86, 131.07, 127.08,
123.88, 103.34, 51.06, 34.49, 19.31.
Compound 11a:[24a] Pale yellow solid, Mp: 158-160 C ; H NMR
(400 MHz, CDCl3) δ: 7.29-7.27 (m, 2H), 7.22-7.18 (m, 2H), 7.14-
7.10 (m, 1H), 5.67 (br.s, 1H), 4.99 (s, 1H), 4.13-4.04 (m, 4H) 2.33
(s, 6H), 1.24-1.20 (m, 6H); 13C NMR (100MHz, CDCl3) δ: 167.59,
147.72, 143.78, 127.99, 127.80, 126.07, 104.17, 59.71, 39.59,
19.60, 14.22; EI-MS (m/z): 329.2 (M+).
3.7 Typical procedure for the synthesis of N-heterocyclic
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1
compounds catalyzed by recovered catalyst 1a
To a 50 ml round-bottomed flask were added catalyst 1a (15.2
mg, 0.02 mmol), o-phenylenediamine (108 mg, 1 mmol) and
PHCHO (212 mg, 2 mmol). Then the mixture was stirred for 30min
monitored by TLC analysis until the intermediate were consumed
completely. The mixture was extracted with CH2Cl2 (3 × 10 mL)
and the catalyst was collected by means of filtration for the next
reaction cycle (Table 5). The solvent was removed by evaporation
in a vacuum and was then subjected to silica gel column
chromatography on silica gel (200-300 mesh) (petroleum
ether/ethyl acetate=5/1, v/v). The same procedure for the
synthesis of other N-heterocyclic compounds catalyzed by
recovered catalyst 1a.
Compound 11b:[24a] Yellow solid, Mp: 161-163 C; H NMR (400
MHz, CDCl3) δ: 7.19 (d, J = 8.8 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H),
5.67 (br.s, 1H), 4.93 (s, 1H), 4.13-4.04 (m, 4H), 3.75 (s, 3H), 2.32
(s, 6H), 1.24-1.21 (m, 6H); 13C NMR (100MHz, CDCl3) δ: 167.65,
157.80, 143.53, 140.27, 128.91, 113.11, 104.31, 59.66, 55.09,
38.67, 19.55, 14.23; EI-MS (m/z): 359.2 (M+).
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Compound 11c:[24a] Yellow solid, Mp: 230-232 C; H NMR (400
MHz, d6-DMSO) δ: 9.09 (s, 1H), 8.72 (s, 1H), 6.95 (d, J = 8.4 Hz,
2H), 6.59 (d, J = 8.8 Hz, 2H), 4.76 (s, 1H), 4.03-3.95 (m, 4H), 2.25
Conclusions
(s, 6H), 1.16 (t, J = 7.0 Hz, 6H); 13C NMR (100MHz, d6-DMSO) δ:
167.58, 155.90, 145.24, 139.40, 128.76, 114.98, 102.76, 59.35,
38.33, 18.67, 14.65; EI-MS (m/z): 345.2 (M+).
In summary, we have demonstrated a versatile method for the
synthesis of N-heterocyclic compounds, such as benzimidazoles,
benzodiazepines, dihydropyrimidinones and dihydropyridines using
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Compound 11d:[24a] Yellow solid, Mp: 147-148 C; H NMR (400
MHz, CDCl3) δ: 7.23-7.20 (m, 2H), 7.17-7.15(m, 2H), 5.86 (br.s,
1H), 4.96 (s, 1H), 4.13-4.04 (m, 4H), 2.31 (s, 6H), 1.22 (t, J = 7.2
Hz, 6H); EI-MS (m/z): 363.2 (M+).
zirconocene bis(perfluorobutanesulfonate) as
a catalyst. The
approach has merits of high yield, operational simplicity, mild
solvent-free reaction conditions and good recyclability of the
catalyst. On account of its stability as well as storability, the
complex should find a broad range of utility.
1
Compound 11e:[24a] Yellow solid, Mp: 162-164 oC; H NMR (400
MHz, CDCl3) δ: 7.34-7.30 (m, 2H), 7.17-7.14 (m, 2H), 5.90 (br. s,
1H), 4.95 (s, 1H), 4.13-4.04 (m, 4H), 2.31(s, 6H), 1.22 (t, J = 7.2
Hz, 6H); EI-MS (m/z): 407.1 (M+).
Acknowledgements
1
Compound 11f: [24b] Yellow solid, Mp: 148-150 oC; H NMR (400
The authors thank the National Natural Science Foundation of
China (No 21273068, 21373003), the NSF of Hunan Province
(2014JJ7027), and the Fundamental Research Funds for the Central
Universities, Hunan university, for financial support.
MHz, CDCl3) δ: 7.32-7.28 (m, 1H), 7.10-7.08 (m,1H), 7.01-6.97
(m, 1H), 6.92-6.87 (m, 1H), 5.68 (br. s, 1H), 5.24 (s, 1H), 4.09-4.01
(m, 4H), 2.31 (s, 6H), 1.18 (t, J = 7.2 Hz, 6H)；EI-MS (m/z): 347.2
(M+).
1
Compound 11g: [24b] Yellow solid, Mp: 169-170 oC; H NMR (400
Appendix A. Supplementary material
MHz, CDCl3) δ: 7.73 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H),
7.46 (t, J = 7.4 Hz, 1H), 7.24 (d, J = 7.2 Hz, 1H), 5.85 (br. s, 1H),
5.74 (s, 1H), 4.15-4.09 (m, 2H), 4.04-3.96 (m, 2H), 2.32 (s, 6H),
1.16 (t, J = 7.2 Hz, 6H); EI-MS (m/z): 374.2 (M+).
All compounds are known from the literature except compound
6e, the copies of H NMR and MS spectra can be found via the
“Supplementary Content” section of this article’s webpage.
1
Compound 11h:[24a] Pale yellow solid, Mp: 162-163 C ; H NMR
(400 MHz, CDCl3) δ: 8.14 (s, 1H), 8.02-7.99 (m, 1H), 7.65 (d, J =
7.6 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 6.30 (br.s, 1H), 5.10 (s, 1H),
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1
References and notes
1.
(a) Schutz, H. Benzodiazepines, Springer, Heidelberg, 1982, 2,
240; (b) Landquist, J. K. In Comprehensive Heterocyclic
4.13-
4.05 (m, 4H) 2.35 (s, 6H), 1.23 (t, J = 7.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ: 167.27, 150.02, 148.09, 145.11, 134.57,
Chemistry, Katritzky, A. R. and Rees, C. W.; Eds., Pergamon,
128.63, 123.09, 121.32, 103.11, 60.01, 39.94, 19.45, 14.23.
Oxford, 1984, 1,166; (c) Scott, L. J.; Dunn, C. J.; Mallarkey,
G.; Sharpe, M. Drugs 2002, 62, 1503; (d)Nakano, H.; Inoue,
T.; Kawasaki, N.; Miyataka, H.; Matsumoto, H.; Taguchi, T.;
Inagaki, N.; Nagai, H.; Satoh, T. Bioorg. Med. Chem. 2000, 8,
373; (e) Tewari, N.; Dwivedi, N.; Tripathi, R. P. Tetrahedron
Lett. 2004, 45, 9011; (f) Baraldi, P. G.; Chiarini, A.; Budriesi,
R.; Roberti, M.; Casolar, A.; Manfredini, S.; Simoni, D.;
Zanirato, V.; Varani, K.; Borea, P. A. Drug Des. Delivery
1989, 5, 13.
(a) Atwal, K. S.; Rovnyak, G. C.; Kimball, S. D.; Floyd, D.
M.; Moreland, S.; Swanson, B. N.; Gougoutas, J. Z.;
Schwartz, J.; Smillie, K. M.; Malley, M. F. J. Med. Chem.
1990, 33, 2629; (b) Di Braccio, M.; Grossi, G.; Romoa, G.;
Vargiu, L.; Mura, M.; Marongiu, M. E. Eur. J. Med. Chem.
2001, 36, 935; (c) Gordeev, M. F.; Patel, D. V.; Gordon, E. M.
J. Org. Chem. 1996, 61, 924; (d) Bocker, R. H.; Guengerich,
E. P. J. Med. Chem. 1986, 29, 1596; (e) Hirashima, H.;
Suzuki, T.; Ishida, T.; Noji, S.; Yata, S.; Ando, I.; Komats, M.;
Ikeda, S. and Hashimoto, H. J. Med. Chem. 2006, 49, 4721.
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1
Compound 11i: [24b] Yellow solid, Mp: 148-150 C; H NMR (400
MHz, CDCl3) δ: 7.23 (d, J = 7.2 Hz, 2H), 7.17 (t, J = 7.6 Hz, 2H),
7.07 (t, J = 7.2 Hz, 1H), 6.15 (d, J = 8.0 Hz, 1H), 6.08-6.03 (m,
1H), 5.85 (br. s, 1H), 4.54 (d, J = 6.4 Hz, 1H), 4.14-4.05 (m, 4H),
2.24 (s, 6H), 1.21 (t, J = 7.2 Hz, 6H); EI-MS (m/z): 355.2 (M+).
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1
Compound 11j:[24a] Pale yellow solid, Mp: 160-161 C ; H NMR
(400 MHz, CDCl3) δ: 7.11 (s, 1H), 6.40 (s, 1H), 6.11 (d, J = 2.8 Hz,
1H), 5.85 (d, J = 2.8 Hz, 1H), 5.12 (s, 1H), 4.13-4.03 (m, 4H), 2.22
2.
(s, 6H), 1.18 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ:
167.69, 158.78, 145.63, 140.79, 110.01, 104.39, 100.35, 59.84,
33.37, 19.27, 14.32.
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1
Compound 11k: [24c] Yellow solid, Mp: 194-196 C; H NMR (400
MHz, CDCl3) δ: 7.27-7.25 (m, 2H), 7.21 (t, J = 7.4Hz, 2H), 7.13 (t,
J = 7.0 Hz, 1H), 5.80 (br. s, 1H), 5.00 (s, 1H), 3.64 (s, 6H), 2.33 (s,
6H); EI-MS (m/z): 301.2 (M+).

3.
(a) Dudd, L. M.; Venardou, E.; Garcia-Verdugo, E.; Licence,
H.; Yin, S. F. Catal. Commun. 2014, 43, 184; (c) Zhang, X.
H.; Lou, C.; Li, N. B.; Xu, X. H.; Qiu, R. H.; Yin, S. F. J.
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ACCEPTED MANUSCRIPT
Highlights
►
►
►
►
A general and mild protocol for the synthesis N-heterocyclic compounds
Catalytic amount of [Cp2Zr(H2O)2] [OSO2C4F9]2 exhibited higher catalytic activity.
The good-to-excellent yields were obtained under solvent-free condition.
Catalyst can be reused without significant loss of activity in a test of five cycles.

ACCEPTED MANUSCRIPT
Graphical Abstract
Zirconocene bis(perfluorobutanesulfonate) is air- and water-stable and proved to be
ionic on basis of conductivity measurements. It exhibits high catalytic efficiency for
the synthesis of N-heterocyclic compounds under solvent-free condition, such as
benzimidazoles, benzodiazepines, dihydropyrimidinones and dihydropyridines under
mild condition. Furthermore, it can be reused without loss of activity in a test of five
cycles. This catalytic system affords a simple and efficient approach for the synthesis
of N-heterocyclic compounds.

ACCEPTED MANUSCRIPT
Air-stable zirconocene bis(perfluorobutanesulfonate) as a
highly efficient catalyst for synthesis of N-heterocyclic
compounds
a
a
Jinying Wang, † Ningbo Li, † Renhua Qiu,*a Xiaohong Zhang a, Xinhua Xu,*a,b and
Shuangfeng Yin*a
aCollege of Chemistry and Chemical Engineering, Hunan University, Changsha,
410082, China
bState Key Laboratory of Elemento-Organic Chemistry, Nankai, University, Tianjing
300071, China
†These authors contributed equally to this work.
Fax: (+ 86) 731-88821546; E-mail: renhuaqiu@hnu.edu.cn; xhx1581@hnu.edu.cn;
sf_yin@hnu.edu.cn
1

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1HNMR Spectra of Complex 1a
1H NMR of 1a in CD3CN
13C NMR of 1a in CD3CN
2

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19F NMR of 1a in CD3CN
1HNMR Spectra and Ms of All compounds
1H NMR of 4a in CDCl3
3

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Ms of 4a
1H NMR of 4b in CDCl3
4

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13C NMR of 4b in CDCl3
Ms of 4b
5

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1H NMR of 4c in CDCl3
wjy-141119-3 #7 RT: 1.20 AV:
T: EI Full ms [ 49.50-500.50]
105.1
1 NL: 5.20E6
+
c
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
312.2
208.2
313.2
311.2
106.1
77.1
207.2
79.1
209.2
221.2
206.2
200
192.2
314.3
63.1
116.1
357.2
350
165.1
152.1
150
244.1
252.2
298.2
300
50
100
250
400
450
500
m/z
Ms of 4c
6

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N
N
N(CH3)2
N(CH3)2
1H NMR of 4d in CDCl3
Ms of 4d
7

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1H NMR of 4e in CDCl3
wjy-141126-352 #6 RT: 1.03 AV:
T: + c EI Full ms [ 49.50-500.50]
1 NL: 1.06E6
352.1
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
125.1
354.1
127.1
355.1
356.1
351.1
228.1
10
90.1
192.1
191.1
227.1
207.1
5
57.1
230.1
241.1
63.1
128.1
149.1
91.1
100
317.1
357.1
281.1
111.1
264.2
349.1
350
50
150
200
250
300
400
450
500
m/z
Ms of 4e
8

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1H NMR of 4f in CDCl3
Ms of 4f
9

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1H NMR of 4g in CDCl3
wjy-141126-266 #4 RT: 0.80 AV:
T: + c EI Full ms [ 49.50-500.50]
1 NL: 2.85E6
81.1
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
264.2
15
53.1
265.2
10
90.1
184.1
5
77.1
156.1
102.1
100
207.2
200
129.1
235.2
266.2
m/z
50
150
250
300
350
400
450
500
Ms of 4g
10

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1H NMR of 4h in CDCl3
13C NMR of 4h in CDCl3
11

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wjy-141126-386 #10 RT: 1.77 AV:
T: + c EI Full ms [ 49.50-500.50]
1
NL: 2.78E6
141.1
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
384.2
385.2
142.2
115.1
125.1
383.2
10
5
244.2
153.1
154.1
242.2
228.1
386.2
387.3
352.1
351.1
63.1
192.2
89.1
245.2
202.2
265.2
m/z
382.2
281.1
300
50
100
150
200
250
350
400
450
500
Ms of 4h
1H NMR of 4i in CDCl3
12

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13C NMR of 4i in CDCl3
1H NMR of 6a in CDCl3
13

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13C NMR of 6a in CDCl3
Ms of 6a
14

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1H NMR of 6b in CDCl3
Ms of 6b
15

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1H NMR of 6c in CDCl3
Ms of 6c
16

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1H NMR of 6d in CDCl3
Ms of 6d
17

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1H NMR of 6e in CDCl3
13C NMR of 6e in CDCl3
18

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wjy-141127-384 #7 RT: 1.30 AV:
1 SB: 2 1.64-1.81 NL: 3.61E6
T:
+
c
EI Full ms
[
49.50-500.50]
271.3
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
173.2
272.3
286.3
384.4
369.4
133.1
231.3
55.1
174.2
385.4
386.4
172.2
187.2
200
92.1
69.1
145.1
150
229.2
287.3
300
131.1
232.3
250
269.3
341.4
327.3
355.3
100
350
400
450
500
m/z
Ms of 6e
1H NMR of 6f in CDCl3
19