Halogenation of pyrazoles using N-halosuccinimides in CCl4 and in water

Article abstract of DOI:10.1080/00397910600978549

Reaction of pyrazoles with N-halosuccinimides (NXS, X=Br, Cl) in either CCl4 or water gave 4-halopyrazoles in excellent yields. The reaction was carried out under mild conditions and did not require any catalysts or special precautions. The reaction provides an efficient method for 4-C halogenation of pyrazoles. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600978549

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Halogenation of Pyrazoles Using
N‐Halosuccinimides in CCl4 and in Water
Zhi‐Gang Zhao a & Zhong‐Xia Wang a
a Department of Chemistry, University of Science and Technology of China,
Hefei, Anhui, China
Available online: 25 Jul 2007
To cite this article: Zhi‐Gang Zhao & Zhong‐Xia Wang (2007): Halogenation of Pyrazoles Using
N‐Halosuccinimides in CCl4 and in Water, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:1, 137-147
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Synthetic Communicationsw, 37: 137–147, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600978549
Halogenation of Pyrazoles Using
N-Halosuccinimides in CCl4 and in Water
Zhi-Gang Zhao and Zhong-Xia Wang
Department of Chemistry, University of Science and Technology
of China, Hefei, Anhui, China
Abstract: Reaction of pyrazoles with N-halosuccinimides (NXS, X ¼ Br, Cl) in either
CCl4 or water gave 4-halopyrazoles in excellent yields. The reaction was carried out
under mild conditions and did not require any catalysts or special precautions. The
reaction provides an efficient method for 4-C halogenation of pyrazoles.
Keywords: carbon tetrachloride, halogenation, N-halosuccinimides, pyrazoles, water
INTRODUCTION
A large number of compounds with important biological and pharmaceutical
activities contain key substructures of 4-halopyrazoles.[1,2] 4-Halopyrazoles
have also been used in the synthesis of biologically active compounds and
cross-coupling reactions such as the Suzuki reaction,[3–5] Heck reaction,[1,6]
Sonogashira reaction,[2,7] and other important reactions.[8] 4-Halopyrazoles
are usually prepared by halogenation of pyrazoles using various halogenating
agents such as Cl2, HOCl, Br2, KI/KIO3, ICl, I2/PhI(OAc)2, and KICl2.[9]
N-Halosuccinimides (NXS) have also been used in the halogenations of
pyrazoles.[1,6,10] However, as indicated by H. A. Stefani et al., the examination
of previously reported methods reveals serious synthetic drawbacks, such as
mixture of products, long reaction times, high temperatures, and use of
catalysts.[11] Recently, Stefani and coworkers reported the halogenation of
pyrazoles using NXS under ultrasound irradiation, giving 4-halopyrazoles in
Received in R.O.C. April 12, 2006
Address correspondence to Zhong-Xia Wang, Department of Chemistry, University
of Science and Technology of China, Hefei, Anhui 230026, China. E-mail: zxwang@
ustc.edu.cn
137

138
Z.-G. Zhao and Z.-X. Wang
good yields.[11] These halogenation reactions using NXS are usually carried
out in organic solvents and require an excessive quantity of NXS and an N2
atmosphere.[1,6,10,11] Here we report a highly efficient and convenient halo-
genation reaction of pyrazoles using NXS without the need for any catalysts
and protection from oxygen and water.
RESULTS AND DISCUSSION
Reaction of pyrazoles 1 and NXS, (X ¼ Br, Cl) in CCl4 or water at the appro-
priate temperature and time afforded 4-bromopyrazoles 2 or 4-cholopyrazoles
3 (Scheme 1). Most reactions gave excellent yields (Table 1). Many of the
reactions could be completed in a short time (0.5–2 h; see Table 1) at room
temperature or a little higher temperature depending on the reactivity of the
substrates. Enhancing the reaction temperature could obviously accelerate
the reactions. For example, reaction of N-bromosuccinimide (NBS) with 1a,
1c, 1e and 1f at 258C could be completed in 0.5–1 h. However, if the temp-
erature was enhanced to 358C, the reaction could be complete in about
15 min. These reactions did not need the existence of catalysts and an N2
atmosphere. They went along well in either CCl4 or water (distilled water
or tap water). Actually the reaction could also proceed well in other organic
solvents. We examined the reaction of 1c with NBS in various organic
solvents, including CHCl3, CH2Cl2, CH3COOEt, THF, and EtOH. In each
case, the reaction gave 2c in 90–95% yield. In most reactions that we
studied, H2O is superior to CCl4. The reactions carried out in water often
exhibited a higher reaction rate and required lower reaction temperature and
shorter reaction time. In some cases, the reaction could only proceed in
water. For example, reaction of N-chlorosuccinmide (NCS) with 1i could
not proceed in CCl4 even under refluxing conditions, while in water the
reaction could be completed at 808C (bath temperature) in 2 h. A similar
result was also observed in the reaction of 1k with NBS.
The activity of the pyrazoles and NXS greatly affects the halogenation
reactions. NBS was more active than NCS in the reactions. For instance,
Scheme 1. a: R ¼ R1 ¼ H; b: R ¼ H, R1 ¼ Me; c: R ¼ Me, R1 ¼ H; d:
R ¼ R1 ¼ Me; e: R ¼ Me, R1 ¼ Ph; f: R ¼ Me, R1 ¼ o-MeC6H4; g: R ¼ Me,
R1 ¼ o-NO2C6H4; h: R ¼ Me, R1 ¼ 2-(6-MeC5H3N); i: R ¼ Me, R1 ¼ PhCO; j:
R ¼ Ph, R1 ¼ H; k: R ¼ Ph, R1 ¼ o-NO2C6H4; l: R ¼ t-Bu, R1 ¼ H.

Halogenation of Pyrazoles
139
Table 1. Reaction of pyrazoles with NXS (X ¼ Cl, Br) in CCl4 or in H2O
Starting
material
NXS
(equiv)
Temp
(8C)a
Time
(h)
Yield
(%)
Entry
Solvent
Product
1
2
3
4
5
1a
1a
1a
1a
1b
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
25
25
25
25
25
2
2a
2a
3a
3a
2b
98
98
98
80
96
0.5
2
3
2
6
7
8
9
1b
1b
1b
1c
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
25
25
50
25
1
2
6
2
2b
3b
3b
2c
96
92
85
99
10
11
12
13
14
1c
1c
1c
1d
1d
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
25
25
25
25
25
0.5
1
2c
3c
3c
2d
2d
97
99
96
99
96
1
2
2
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
1d
1d
1e
1e
1e
1e
1f
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.5) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (2.0) H2O
NBS (1.0) CCl4
50
25
25
25
50
50
25
25
25
25
25
25
80
70
50
25
60
60
90
80
90
80
50
50
70
80
90
1
2
3d
3d
99
95
99
99
99
98
99
99
97
97
99
99
—
97
99
98
96
95
—
98
—
97
98
98
98
97
—
2
2e
2e
2
1
3e
3e
2
2
2f
1f
2
2f
1f
2
3f
1f
2
3f
2g
1g
1g
1g
1g
1h
1h
1h
1h
1i
3
2
2g
3
Mixture
3g
2h
2
2
0.5
2
2vh
3h
2
3h
Mixture
2i
NRb
3i
7
1i
2
1i
12
2
1i
1j
3
2j
1j
3
2j
1j
3
3j
1j
1k
5
12
3j
NRb
(continued)

140
Z.-G. Zhao and Z.-X. Wang
Table 1. Continued
Starting
material
NXS
(equiv)
Temp
(8C)a
Time
(h)
Yield
(%)
Entry
Solvent
Product
42
43
44
45
46
47
48
1k
1k
1k
1l
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
NBS (1.0) CCl4
NBS (1.0) H2O
NCS (1.0) CCl4
NCS (1.0) H2O
110
90
12
12
12
3
2k
NRb
NRb
2l
98
—
—
99
99
99
98
110
35
1l
35
70
3
2l
1l
2
3l
1l
70
3
3l
aBath temperature.
bNR ¼ no reaction.
reaction of 1g with NBS in water could proceed at room temperature very
well, whereas the reaction with NCS occurred at 708C. The activity of
pyrazoles was affected by the substituted groups attached on the pyrazole
rings. 3,5-Diphenylpyrazoles exhibited obviously less reactivity than
pyrazoles or 3,5-dimethylpyrazoles. This can be proved by comparing the
reactivity of 3,5-diphenylpyrazole with 3,5-dimethylpyrazole toward NXS.
Reaction of the former with NBS in water was completed at 508C in 3 h
(entry 38 in Table 1), whereas the reaction of the latter with NBS in water
can be completed at room temperature in 30 min (entry 10 in Table 1). 3,5-
Di-t-butylpyrazole also showed less reactivity than 3,5-dimethylpyrazole.
This is ascribed to steric hindrance of t-butyl groups. N-Substituted groups
on the pyrazole rings also greatly affect the reactivity of pyrazoles.
Electron-withdrawing groups obviously decrease the activity of the
pyrazoles in the halogenation reactions. For example, reaction of 1i with
NBS in CCl4 gave a mixture under refluxing conditions, and no reaction
occurred even with NCS under refluxing for 12 h in CCl4 (entry 35 in
Table 1). Pyrazoles 1g, 1h, and 1k showed similar reactivity.
The reactions listed in Table 1 usually required only an equivalent of NXS.
However, chloronation of 1i and 1j in H2O required 1.5 and 2 equivalent of NCS,
respectively. Otherwise, only a mixture was obtained. In addition, we also
found that the product of reaction of 1a with 2 equivalent of NBS was still 2a.
Compound 4 showed different reactivity from those pyrazoles mentioned
previously (Scheme 2 and Table 2). Compound 4 reacted with an equivalent of
NBS to afford a mixture containing compound 5, the starting material, and an
unidentified species either in CCl4 or in water. Treatment of 4 with 2 equiv of
NBS in CCl4 gave the single compound 5, whereas a similar reaction in water
formed a mixture. Use of 3 equivalent of NBS in the reaction led to formation
of compound 6 both in CCl4 and in water. Reaction of 4 with NCS in a
different ratio in water always gave a mixture. The products of the reaction
in CCl4 depend on the ratio of 4 to NCS:1:1 ratio gives an unidentified

Halogenation of Pyrazoles
141
Scheme 2.
mixture, 1:2 ratio forms a mixture of 7, 8, and minor impurities, and 1:3 ratio
produces compound 9 with minor impurities. These are ascribed to the acti-
vation of amino group to the phenyl ring.
The separation of the products is usually simple. When CCl4 was used as
the solvent, after filtrating off the by-product, succinimide, the filtrate was
washed with water and then dried. The product was obtained by removing
the solvent under reduced pressure. When water was used as the solvent,
the solid product was isolated by simple filtration, and the liquid product
was obtained by extracting with CCl4. However, solid products such as 2a
and 2b are soluble in water. They were isolated by extracting with CCl4.
Some products such as 2c are partly soluble in water. This requires that less
Table 2. Halogenations of 4 with NXS (X ¼ Cl, Br) in CCl4 or H2O
NXS
(equiv)
Temp.
(8C)a
Time
(h)
Yield
(%)
Entry
Solvent
Product
1
2
NBS (1.0)
NBS (1.0)
NBS (2.0)
NBS (2.0)
NBS (3.0)
NBS (3.0)
NCS (1.0)
NCS (1.0)
NCS (2.0)
NCS (2.0)
NCS (3.0)
NCS (3.0)
CCl4
H2O
CCl4
H2O
CCl4
H2O
CCl4
H2O
CCl4
H2O
CCl4
H2O
25
25
25
25
25
25
25
25
40
25
40
25
2
2
2
3
8
5
6
6
2
6
3
8
Mixture
Mixture
5
—
—
98
—
97
95
—
—
—
—
85a
—
3
4
Mixture
6
5
6
6
7
Mixture
Mixture
7 þ 8
Mixture
9
8
9
10
11
12
Mixture
aBath temperature.

142
Z.-G. Zhao and Z.-X. Wang
water was applied as solvent and to wash the products. Otherwise, the yields
were obviously decreased. When we ran the reaction of 1c with NBS in the
usual amount of water and washed the product as usual, only 85% yield of
2c was obtained.
CONCLUSIONS
In summary, a convenient and highly efficient method of halogenation of
pyrazoles using NXS (X ¼ Br, Cl) has been achieved. The reactions can be
carried out in CCl4 or in water, without the need for any protection from
air. Water was proved to be excellent solvent in the reactions, exhibiting
a higher reaction rate than in CCl4 and convenient product isolation. The
effects of the substituted groups on the pyrazoles are discussed.
The pyrazoles with electron-withdrawing groups showed obviously less
reactivity. The reactions can usually be completed using an equivalent of
NXS, except for the reactions of NCS with 1i and 1j, respectively, in water,
which required more than 1 equivalent of NXS. We also found that the
reaction of 2-(3,5-dimethylpyrazol-1-yl)aniline with NXS (X ¼ Br, Cl)
always gave di- or trihalogenated compounds depending on the ratio of the
reactants.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Bruker AV300 spectrometer, and
the chemical shifts are referenced to internal solvent resonances. IR spectra
were recorded on a Bruker Vector-22 spectrometer. Elemental analyses (for
the new compounds) were performed by the Analytical Centre of the Univer-
sity of Science and Technology of China. The starting materials 1b–1g, 1i, 1j,
1k, 1l, and 4 were prepared according to the procedures described in the lit-
erature.[12–16] Compound 1h was prepared by refluxing a mixture of
2-hydrazino-6-methyl- pyridine and acetyl acetone in acetic acid. Other
regents and solvents were obtained from commercial suppliers.
General Procedure of Halogenations of Pyrazoles in CCl4
A mixture of appropriate pyrazole (4 mmol) and NXS (see Tables 1 and 2) in
CCl4 (8 mL) was stirred at an appropriate temperature and time. The progress
of the reaction was monitored by thin-layer chromatography (TLC) or the dis-
appearance of the NXS at the bottom of the flask. The by-product succinimide
was filtered off and washed with CCl4 (5 mL). The filtrate was washed with
water (2 ꢀ 10 mL) and dried with MgSO4. The solvent was removed under
reduced pressure. The products were obtained in good purity indicated by
1H NMR spectra.

Halogenation of Pyrazoles
143
General Procedure of Halogenations of Pyrazoles in H2O
A mixture of appropriate pyrazole (4 mmol) and NXS (see Table 1 and
Table 2) in H2O (5 mL) was stirred at appropriate temperature and time.
1
The progress of the reaction was monitored by TLC or the H NMR spectra
of the product (the disappearance of the signal of the CH of the pyrazole ring).
For oily and water-soluble solid products, the reaction mixture was
extracted with CCl4 (2 ꢀ 5 mL) and the extract was dried with MgSO4. The
solvent was removed under reduced pressure. The 4-halopyrazoles were
1
obtained in good purity as indicated by H NMR spectra.
For other solid products, the precipitate was collected by filtration,
washed with water (2 ꢀ 8 mL), and dried in air. The products so obtained
1
were in good purity as indicated by H NMR spectra.
The samples for elemental analysis were purified by recrystallizing from
appropriate solvents (for the solid samples) or by column chromatography (for
the liquid samples).
Characterization of the Products
2a: Colorless crystals, mp: 98–1008C (lit.:[17] 96–978C). 1H NMR (300 MHz,
CDCl3): d 7.53 (s, 2H, CH), 10.10 (s, 1H, NH).
3a: Colorless crystals, mp: 75–768C (lit.:[18] 76–778C). 1H NMR (300 MHz,
CDCl3): d 7.55 (s, 2H, CH), 10.39 (b, 1H, NH).
1
2b: Red oil. H NMR (300 MHz, CDCl3): d 3.82 (s, 3H, CH3), 7.31 (s, 1H,
CH), 7.37 (s, 1H, CH).
3b: Yellow oil. 1H NMR (300 MHz, CDCl3): d 3.78 (s, 3H, CH3), 7.26 (s, 1H,
CH), 7.32 (s, 1H, CH).
2c: Colorless crystal, mp: 123 2 1248C (lit.:[19] 123–1248C). 1H NMR
(300 MHz, CDCl3): d 2.26 (s, 6H, CH3), 9.28 (b, 1H, NH).
1
3c: Colorless crystals, mp: 117 2 1188C (lit.:[20] 117.5–118.58C). H NMR
(300 MHz, CDCl3): d 2.25 (s, 6H, CH3).
2d: Yellow oil. 1H NMR (300 MHz, CDCl3): d 2.21 (s, 3H, CH3), 2.23 (s, 3H,
CH3), 3.75 (s, 3H, CH3).
3d: Light yellow oil. 1H NMR (300 MHz, CDCl3): d 2.13 (s, 3H, CH3), 2.14
(s, 3H, CH3), 3.65 (s, 3H, CH3).
2e: Yellow oil. 1H NMR (300 MHz, CDCl3): d 2.31 (s, 6H, CH3), 7.38–7.50
(m, 5H, Ph).

144
Z.-G. Zhao and Z.-X. Wang
3e: Yellow oil. 1H NMR (300 MHz, CDCl3): d 2.30 (s, 6H, CH3), 7.37–7.47
(m, 5H, Ph).
2f: Red orange oil. Anal. calc. for C12H13BrN2: C, 54.36%; H, 4.94%; N,
10.56%; found: C, 54.44%; H, 5.00%; N, 10.40%. 1H NMR (300 MHz,
CDCl3): d 1.98 (s, 3H, CH3), 1.99 (s, 3H, CH3), 2.22 (s, 3H, CH3), 7.09–
7.28 (m, 4H, C6H4). 13C NMR (75.5 MHz, CDCl3): d 10.70, 12.42, 17.25,
94.57, 126.63, 127.79, 129.36, 131.02, 136.08, 138.40, 138.67, 147.05. IR
(KBr): n (cm21) 3067w, 2919m, 2855w, 1631w, 1606w, 1585w, 1546m,
1502vs, 1466m, 1372m, 1289w, 1270w, 1122w, 1078s, 1046m, 1028m,
943w, 816w, 779m, 763s, 721s, 671w, 605w.
3f: Yellow orange oil. Anal. calc. for C12H13ClN2: C, 65.31%; H, 5.94%; N,
12.69%; found: C, 65.69%; H, 5.56%; N, 12.34%. 1H NMR (300 MHz,
CDCl3): d 1.97 (s, 6H, CH3), 2.21 (s, 3H, CH3), 7.09–7.30 (m, 4H, C6H4).
13C NMR (75.5 MHz, CDCl3): d 9.83, 11.49, 17.28, 108.27, 126.67, 127.87,
129.38, 131.07, 136.18, 136.66, 138.61, 145.57. IR (KBr): n (cm21) 3062w,
3030w, 2957m, 2925m, 2860w, 1607w, 1585w, 1558m, 1504vs, 1473m,
1381m, 1293w, 1272w, 1097s, 1032m, 985w, 945w, 818w, 779m, 763s,
722m.
1
2g: Yellow powder, mp: 103–1048C. H NMR (300 MHz, CDCl3): d 2.12
(s, 3H, CH3), 2.19 (s, 3H, CH3), 7.40 (d, 1H, J ¼ 7.2 Hz, C6H4), 7.52–7.56
(m, 1H, C6H4), 7.63–7.68 (m, 1H, C6H4), 7.9327.97 (m, 1H, J ¼ 8.0 Hz,
C6H4).
3g: Yellow powder, mp: 97–988C. Anal. calc. for C11H10ClN3O2: C, 52.50%;
H, 4.01%; N, 16.70%; found: C, 52.08%; H, 3.93%; N, 16.76%. H NMR
1
(300 MHz, CDCl3): d 2.11 (s, 3H, CH3), 2.19 (s, 3H, CH3), 7.40 (d, 1H,
J ¼ 7.8 Hz, C6H4), 7.54 (t, 1H, J ¼ 7.5 Hz, C6H4), 7.66 (t, 1H, J ¼ 7.5 Hz,
C6H4), 7.95 (m, 1H, Ph). 13C NMR (75.5 MHz, CDCl3): d 9.96, 11.45,
110.18, 125.34, 129.47, 129.81, 132.92, 133.46, 137.39, 146.30, 147.62. IR
(KBr): n (cm21) 3086w, 2987w, 2925w, 2875w, 1608m, 1587w, 1532s,
1507s, 1452m, 1418m, 1384m, 1359s, 1230m, 1257w, 1113m, 1090m,
1028m, 956w, 852m, 802w, 780m, 752m, 703m, 661w, 635w, 587w.
2h: Light yellow powder, mp: 53–548C. Anal. calc. for C11H12BrN3: C,
49.64%; H, 4.54%; N, 15.79%; found: C, 49.75%; H, 4.50%; N, 15.86%.
1H NMR (300 MHz, CDCl3): d 2.23 (s, 3H, CH3), 2.47 (s, 3H, CH3), 2.56
(s, 3H, CH3), 6.97 (d, 1H, J ¼ 7.5 Hz, Py), 7.49 (d, 1H, J ¼ 8.0 Hz, Py),
7.58–7.63 (m, 1H, Py). 13C NMR (75.5 MHz, CDCl3): d 12.64, 13.56,
24.24, 98.54, 112.70, 120.83, 138.70, 139.08, 148.24, 152.72, 157.08. IR
(KBr): n (cm21) 2981w, 2923m, 2852w, 1601s, 1582s, 1557m, 1484s,
1446vs, 1383s, 1361s, 1286w, 1270w, 1233w, 1180w, 1152w, 1098m,
1056s, 1015m, 880w, 790s, 762m, 730w, 681m, 657w, 606w.

Halogenation of Pyrazoles
145
3h: White powder, mp: 58–598C. Anal. calc. for C11H12ClN3: C, 59.60%; H,
5.46%; N, 18.95%; found: C, 59.71%; H, 5.39%; N, 18.97%. 1H NMR
(300 MHz, CDCl3): d 2.21 (s, 3H, CH3), 2.45 (s, 3H, CH3), 2.54 (s, 3H,
CH3), 6.94 (d, 1H, J ¼ 7.5 Hz, Py), 7.49 (d, 1H, J ¼ 8.0 Hz, Py), 7.56–7.61
(m, 1H, Ph). 13C NMR (75.5 MHz, CDCl3): d 11.60, 12.58, 24.15, 111.49,
112.38, 120.58, 137.26, 138.58, 146.66, 152.76, 156.91. IR (KBr): n (cm21
)
2984w, 2954w, 2924m, 2851w, 1600s, 1583s, 1486s, 1455vs, 1385s, 1365s,
1286w, 1234w, 1180w, 1152w, 1109m, 1060s, 1020m, 881w, 790s, 762m,
730w, 684m, 660w, 620w.
2i: White solid, mp: 60–618C (lit.:[21] 48–498C). 1H NMR (300 MHz,
CDCl3): d 2.19 (s, 3H, CH3), 2.57 (s, 3H, CH3), 7.37–7.42 (m, 2H, Ph),
7.49–7.51 (m, 1H, Ph), 7.86–7.89 (m, 2H, Ph).
3i: White solid. mp: 54–558C. Anal. calc. for C12H11ClN2O: C, 61.42%; H,
4.72%; N, 11.94%; found: C, 61.18%; H, 4.73%; N, 12.01%. 1H NMR
(300 MHz, CDCl3): d 2.19 (s, 3H, CH3), 2.56 (s, 3H, CH3), 7.37–7.42
(m, 2H, Ph), 7.48–7.53 (m, 1H, Ph), 7.88 (d, 2H, J ¼ 7.8 Hz, Ph).
13C NMR (75.5 MHz, CDCl3): d 11.87, 12.41, 114.94, 128.03, 131.48,
132.64, 132.80, 140.43, 149.61, 167.96. IR (KBr): n (cm21) 3069w, 3032w,
2974w, 2931w, 1702vs, 1600m, 1583m, 1490s, 1449s, 1407s, 1378vs,
1343vs, 1276vs, 1206m, 1182m, 1135w, 1084s, 1103w, 1011m, 990s, 935s,
797m, 782m, 712s, 686vs, 624m.
1
2j: White powder, mp: 199–2008C (lit.:[22] 1988C). H NMR (300 MHz,
CDCl3): d 7.42–7.52 (m, 6H, Ph), 7.80–7.82 (m, 4H, Ph).
3j: White powder, mp: 191–1938C (lit.:[23] 203–2048C). 1H NMR (300 MHz,
CDCl3): d 7.38–7.46 (m, 6H, Ph), 7.77–7.79 (m, 4H, Ph).
2k: Yellow crystals, mp: 104–1058C. Anal. calc. for C21H14BrN3O2: C,
60.02%; H, 3.36%; N, 10.00%; found: C, 60.28%; H, 3.38%; N, 10.02%. H
1
NMR (300 MHz, CDCl3): d 7.20–7.43 (m, 11H, Ph þ C6H4), 7.83–7.90
(m, 3H, Ph þ C6H4). 13C NMR (75.5 MHz, CDCl3): d 95.10, 125.25, 127.82,
128.21, 128.45, 128.75, 128.80, 129.37, 129.43, 129.50, 130.12, 131.62,
133.19, 133.38, 143.39, 145.83, 151.17; IR (KBr): n (cm21) 3064w, 3037w,
2924w, 2861w, 1064m, 1584w, 1530s, 1490m, 1449m, 1348s, 1308m,
1188w, 1159m, 1111m, 1068w, 1030w, 964m, 920m, 851w, 769s, 699s, 625w.
2l: White powder, mp: 178–1808C. Anal. calc. for C11H19BrN2: C, 50.97%;
1
H, 7.39%; N, 10.81%; found: C, 50.90%; H, 7.38%; N, 10.84%. H NMR
(300 MHz, CDCl3): d 1.43 (s, 18H, t-Bu). 13C NMR (75.5 MHz, CDCl3): d
28.70, 32.75, 89.01, 153.43. IR (KBr): n (cm21) 3269s, 3083w, 2962s,
2929m, 2871m, 1630w, 1549m, 1485m, 1462m, 1427w, 1386w, 1363m,
1272m, 1231m, 1209w, 1136m, 1048m, 986s, 934w, 760m, 665m, 547w.

146
Z.-G. Zhao and Z.-X. Wang
3l: White powder, mp: 187–1898C. Anal. calc. for C11H19ClN2: C, 61.53%;
1
H, 8.92%; N, 13.05%; found: C, 61.93%; H, 9.03%; N, 12.68%. H NMR
(300 MHz, CDCl3): d 1.35 (s, 18H, t-Bu). 13C NMR (75.5 MHz, CDCl3): d
28.61, 32.46, 104.53, 153.30. IR (KBr): n (cm21) 3261s, 3096w, 2964s,
2926m, 2869m, 1631w, 1556m, 1486m, 1266m, 1431w, 1390w, 1364m,
1275m, 1233m, 1133m, 1070m, 989m, 935w, 764m, 662m, 554w.
5: Light red brown powder, mp: 116–1178C. Anal. calc. for C11H11Br2N3: C,
38.29%; H, 3.21%; N, 12.18%; found: C, 38.18%; H, 3.15%; N, 11.99%. 1H
NMR (300 MHz, CDCl3): d 2.12 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.48 (b, 2H,
NH2), 6.69 (d, 1H, J ¼ 8.5 Hz, C6H3), 7.13 (d, J ¼ 2.1 Hz, Ph), 7.23–7.26
(dd, 1H, J ¼ 8.6, 2.1 Hz, C6H3). 13C NMR (75.5 MHz, CDCl3): d 11.01,
12.53, 95.70, 108.96, 118.08, 126.17, 130.23, 132.75, 139.12, 142.46,
148.57. IR (KBr): n (cm21) 3430m, 3331m, 3052w, 2961w, 2923w, 1612m,
1585w, 1552w, 1502s, 1466m, 1422m, 1378w, 1292w, 1251w, 1159w,
1077m, 1034w, 898w, 849w, 812m, 690w, 634w, 599m.
6: Red powder, mp: 120–1218C. Anal. calc. for C11H10Br3N3: C, 31.17%;
H, 2.38%; N, 9.91%; found: C, 31.07%; H, 2.39%; N, 9.80%. H NMR
1
(300 MHz, CDCl3): d 2.11 (s, 3H, CH3), 2.22 (s, 3H, CH3), 7.10
(d, J ¼ 2.1 Hz, C6H2), 7.55 (d, J ¼ 2.1 Hz, C6H4). 13C NMR (75.5 MHz,
CDCl3): d 11.13, 12.61, 96.18, 108.19, 110.74, 126.10, 129.61, 135.24,
139.28, 141.08, 149.14. IR (KBr): n (cm21) 3408m, 3281m, 3217m,
3178m, 3077w, 2955w, 2920w, 2853w, 1624s, 1558m, 1464vs, 1429m,
1376w, 1352w, 1302w, 1271w, 1226w, 1077s, 1047m, 9878w, 895w,
863m, 807w, 721m, 658m, 632m, 606w, 551m.
1
9: Red solid. H NMR (300 MHz, CDCl3): d 2.11 (s, 3H, CH3), 2.22 (s, 3H,
CH3), 6.93 (d, J ¼ 2.1 Hz, C6H2), 7.27 (d, J ¼ 2.1 Hz, C6H2).
ACKNOWLEDGMENT
We thank the Natural Science Fund of Anhui Province, China, for financial
support.
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