Dramatically accelerated addition under solvent-free conditions: An efficient synthesis of (E)-1,2,4-triazole-substituted alkenes from Baylis-Hillman acetates

Article abstract of DOI:10.1080/00397910802136623

The addition of 1,2,4-triazole to Baylis-Hillman acetates mediated by Et3N was dramatically accelerated under solvent-free conditions to afford (E)-1,2,4-triazole-substituted alkenes 3 with excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802136623

This article was downloaded by: [University of South Carolina ]
On: 22 July 2013, At: 22:14
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Dramatically Accelerated
Addition Under Solvent-
Free Conditions: An Efficient
Synthesis of (E)-1,2,4-Triazole-
Substituted Alkenes from
Baylis–Hillman Acetates
Weihui Zhong a , Yongzhi Zhao a , Baoming Guo a
Peng Wu a & Weike Su a
a College of Pharmaceutical Sciences, Zhejiang
,
University of Technology, Zhejiang Key Laboratory of
Pharmaceutical Engineering, Hangzhou, China
Published online: 12 Sep 2008.
To cite this article: Weihui Zhong , Yongzhi Zhao , Baoming Guo , Peng Wu & Weike Su
(2008) Dramatically Accelerated Addition Under Solvent-Free Conditions: An Efficient
Synthesis of (E)-1,2,4-Triazole-Substituted Alkenes from Baylis–Hillman Acetates,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:19, 3291-3302, DOI: 10.1080/00397910802136623
To link to this article: http://dx.doi.org/10.1080/00397910802136623
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.

However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communications1, 38: 3291–3302, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802136623
Dramatically Accelerated Addition Under
Solvent-Free Conditions: An Efficient Synthesis
of (E)-1,2,4-Triazole-Substituted Alkenes from
Baylis–Hillman Acetates
Weihui Zhong, Yongzhi Zhao, Baoming Guo, Peng Wu, and
Weike Su
College of Pharmaceutical Sciences, Zhejiang University of Technology,
Zhejiang Key Laboratory of Pharmaceutical Engineering, Hangzhou, China
Abstract: The addition of 1,2,4-triazole to Baylis–Hillman acetates mediated
by Et3N was dramatically accelerated under solvent-free conditions to afford
(E)-1,2,4-triazole-substituted alkenes 3 with excellent yields.
Keywords: Acceleration, Baylis–Hillman acetates, solvent-free conditions,
(E)-1,2,4-triazole-substituted alkenes
Since the first report of the Baylis–Hillman reaction in 1972,[1] it has been
widely used as a powerful carbon–carbon bond-forming method in
organic synthesis.[2] During the past decade, Baylis–Hillman adducts
were proven to be useful precursors for the synthesis of a variety of useful
compounds with biological activities.[3,4]
The synthesis of triazole derivatives has recently gained promi-
nence[5] because of their interesting biological properties[6] such as antial-
lergic,
antibacterial,
antifungal,
analgesic,
anti-inflammatory,
antitubercular, anti-HIV, and cytokinin activities. There are several
reports on the synthesis of triazole derivatives from Baylis–Hillman
adducts: (1) Gong et al. reported the reaction of Baylis–Hillman acetate
and 1,2,4-triazole in the presence of 1,4-diazebicyclo[2.2.2]octane
Received November 23, 2007.
Address correspondence to Weike Su, College of Pharmaceutical Sciences,
Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical
Engineering, Hangzhou 310014, China. E-mail: suweike@zjut.edu.cn
3291

3292
W. Zhong et al.
(DABCO) at room temperature for 5 days, and a mixture of products
was obtained with moderate yield,[4d] (2) Chandrasekhar et al. developed
a novel access to substituted triazoles through three-component coupling
of alkynes, Baylis–Hillman adducts, and sodium azide.[7] (3) Sreedhar
et al. claimed 1,4-disubsituted 1,2,3-triazoles can be prepared via nucleo-
philic substitution and 1,3-dipolar cycloaddition.[8] Here we describe an
efficient synthesis of (E)-1,2,4-triazole-substituted alkenes via the
addition of 1,2,4-triazole to Baylis–Hillman acetates mediated by differ-
ent bases under solvent or solvent-free conditions.
Primary experiments were performed under solvent conditions using
Baylis–Hillman acetate adduct 1a as a model compound (Scheme 1).
When this reaction was carried out in ethanol in the presence of
K2CO3, only (E)-1,2,4-triazole-substituted alkene 3a was isolated,
whereas its isomer 4a was not detected either at room temperature
or under reflux. The structure of product 3a was characterized by
1H NMR, 13C NMR, and mass spectra.[4d]
To obtain the optimized condition, the kinds of bases and solvents
were screened, and the results were summarized in Table 1. It was found
that ethanol is an efficient solvent for this addition, whereas water is a
poor medium even under refluxing conditions. Both Et3N and K2CO3
can selectively provide (E)-1,2,4-triazole-substituted alkenes 3a, but
Et3N can provide a higher yield than that of K2CO3 (entries 1, 6). With-
out any bases, the addition was very slow because of the formation of
side product AcOH, and only a trace product was detected by thin-layer
chromatography (TLC) (entry 10), so we chose Et3N to promote this
addition reaction.
On the other hand, we also investigated the nucleophilic substitution
promoted by DABCO. It was found that a mixture of 3a and 4a could be
obtained, and their ratios were largely influenced by reaction temperature
and time. In the presence of DABCO, compound 4a is the main product
at room temperature within a short time (entry 11), whereas 3a was a
major product when elevating the reaction temperature or prolonging
Scheme 1.

(E)-1,2,4-Triazole-Substituted Alkenes
3293
Table 1. The influence of the reaction condition on the product yieldsa
Entry
Bases
Solvents
T (ꢀC)
Time
Product (yield, %)b
1
2
3
4
5
6
7
8
9
10
11
12
13
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
Et3N
Et3N
—
EtOH
EtOH
MeOH
rt
3 h
3 h
5 h
5 h
3 h
4 days
3 h
5 h
5 h
3 h
5
3a (28)
3a (72)
3a (60)
3a (61)
3a (—)c
3a (26)d
3a (75)
80
60
60
100
rt
80
60
60
80
rt
THF=H2O(2=1)
H2O
H2O
EtOH
MeOH
THF-H2O(2=1)
EtOH
EtOH
3a (63)
3a (65)
3a (trace)
3a=4a ¼ 1=5 (24)e
3a=4a ¼ 3=2 (60)e
3a=4a ¼ 9=1 (70)e
DABCO
DABCO
DABCO
EtOH
EtOH
rt
80
48
5
a2.0 mmol of Baylis–Hillman acetates, 2.2 mmol of triazole, and 1.1 mmol of
K2CO3 or 2.2 mmol of Et3N were used.
bIsolated yields based on Baylis–Hillman acetates.
cComplex mixture was obtained.
dThe starting material was recovered.
1
eThe ratio of 3a and 4a was determined from the H NMR spectrum.
the reaction time (entries 12, 13). This result showed that 4a is thermo-
dynamically unstable and thus the isomerization from 4a to 3a would
be favored on standing or under reflux.
Recently, considerable attention has been paid to solvent-free
reactions, which are not only of interest from an environmental point
of view, but in many cases also offer considerable synthetic advantages
in terms of yield, selectivity, and simplicity of the reaction procedure.
To the best of our knowledge, the SN20 substitution of Baylis–Hillman
acetates under solvent-free conditions has not been exploited. When
2 mmol of Baylis–Hillman acetate 1a, 2.2 mmol of 1,2,4-triazole, and
2.2 mmol of Et3N were stirred at room temperature for 15 min, TLC
indicated that the Baylis–Hillman acetate 1a was consumed, and the
SN20 product 3a was isolated with 85% yield (Scheme 2). The possible
explanation is that the high concentration favored this addition, and
the addition rate can be dramatically accelerated under solvent-free
conditions.
Encouraged by this excellent result, we started to explore the reaction
scope with various Baylis–Hillman acetates 1b–n. The results are
summarized in Table 2.

3294
W. Zhong et al.
Scheme 2.
According to Table 2, under solvent-free conditions, the Baylis–
Hillman acetates derived from aromatic aldehydes could produce the
corresponding products 3 with good to excellent yields, and no evident
substitute effect on aromatic rings was observed. However, when R1 is
the alkyl group (i-butyl), the addition is complex, and only 42% of the
corresponding product 3o can be isolated. (entry 15).
In summary, we have disclosed a fast, efficient, and ecofriendly
process for the synthesis of (E)-1,2,4-triazole-substituted alkenes 3 via
Et3N-mediated addition of 1,2,4-triazole to Baylis–Hillman acetates
under solvent-free conditions. The advantages of this method are
Tabel 2. Synthesis of (E)-1,2,4-triazole-substituted alkenes 3 mediated by Et3N
under solvent-free conditionsa
Entry
R1
R2
Time (min)
Product (yield, %)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
p-FC6H4
m-NO2C6H4
C6H5
o-ClC6H4
2-F-6-ClC6H3
2-furyl
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Et
15
15
15
15
14
15
15
15
12
15
15
15
15
15
60
3a (85)c
3b (82)
3c (75)
3d (78)
3e (85)
3f (78)
3g (87)
3h (86)
3i (85)
3j (85)
3k (82)
3l (83)
3m (89)
3n (90)
3o (42)
4-methylthiazol-5-yl
C6H5
m-NO2C6H4
p-FC6H4
o-ClC6H4
2-F-6-ClC6H3
2-furyl
Et
Et
Me
4-methylthiazol-5-yl
i-Bu
a2.0 mmol of Baylis–Hillman acetates, 2.2 mmol of triazole, and 2.2 mmol of
Et3N were used.
bIsolated yields based on Baylis–Hillman acetates.
cThe addition was very slow in the absence of Et3N.

(E)-1,2,4-Triazole-Substituted Alkenes
3295
simple operation, short reaction time, good to excellent yields, and high
regioselectivity. The further studies on the application of Baylis–Hillman
adduct acetates are now in progress in our laboratory.
EXPERIMENTAL
Melting points were recorded on a digital melting-point apparatus
WRS-1B and are uncorrected. Infrared spectra were recorded on Nicolet
Aviatar-370 infrared spectrophotometer. 1H NMR and 13C NMR spectra
were measured on a Varian Mercury plus-400 instrument using CDCl3 as
the solvent with tetramethylsilane (TMS) as an internal standard. Mass
spectra were obtained on a Thermo Finnigan LQC-advantage (ESI) and
Finnigan Truce DSQ (EI). Elemental analyses were carried out on a Vario
EL III instrument. High-resolution mass spectral (HRMS) analyses were
measured on an Apex (Bruker) mass III spectrometer using ESI (electro-
spray ionization) techniques. Baylis–Hillman adducts was prepared from
arylaldehyde derivatives with methyl acrylate or ethyl acrylate. All reagents
are commercially available and were used without further purification.
Typical Procedure for the Synthesis of 3a Under Solvent Conditions
Method A
1,2,4-Triazole (2.2 mmol) was added to a mixture of Baylis–Hillman acet-
ates 1a (2.0 mmol) and triethylamine (2.2 mmol) or K2CO3 (1.1 mmol) in
ethanol (10 mL). The reaction mixture was refluxed for the given time
(Table 1). After completion of the reaction (monitored by TLC), the
solvent was evaporated in vacco, and the crude product was purified
by column chromatography over silica gel (ethyl acetate–petroleum ether
3:2) to afford the corresponding 1,2,4-triazole derivatives 3a.
Method B
DABCO (2.2 mmol) was added to a solution of Baylis–Hillman acetates
1a (2.0 mmol) in ethanol (10 mL), and the mixture was stirred for 10 min
at room temperature. Then 1,2,4-triazole (2.2 mmol) was added, and the
mixture was stirred at room temperature for the given time (Table 1).
After completion of the reaction (monitored by TLC), the solvent
was evaporated in vacco, and the crude product was purified by column
chromatography over silica gel (ethyl acetate–petroleum ether 3:2) to
afford a mixture of 3a and 4a.

3296
W. Zhong et al.
General Procedure for the Synthesis of Product 3 Under
Solvent-Free Conditions
1,2,4-Trizole (2.2 mmol) was added to a mixture of Baylis–Hillman
acetates 1 (2.0 mmol) and Et3N (2.2 mmol), and the mixture was stirred
at room temperature for the given time (Table 2). After the completion
of the reaction (monitored by TLC), CH2Cl2 (20 mL) was added, and
the mixture was washed with brine and dried over sodium sulfate. After
concentrated in vacco, the residue was purified by silica-gel column
chromatography to afford the product 3.
Data
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(4-fluorophenyl)
acrylate (3a)
Colorless crystal, mp: 71.1–72.3 ꢀC; IR (KBr) nmax: 3125, 2949, 1710 cmꢁ1;
1H NMR (400 MHz, CDCl3): dH 8.27 (s, 1H), 8.01 (s, 1H), 7.97 (s, 1H),
7.78 (dd, 2H, J1 ¼ 8.8 Hz, J2 ¼ 6 Hz), 7.16 (dd, 2H, J1 ¼ J2 ¼ 8.8 Hz), 5.17
(s, 2H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3) d 166.6, 163.3 (d,
1JC,F ¼ 250.2 Hz), 151.5, 144.1, 144.0, 131.6, 131.5, 129.8, 124.8, 115.8,
115.7, 52.2, 45.8; MS m=z (%): 261 (Mþ, 45), 202 (100), 133 (80). Anal.
calcd. for C13H12FN3O2: C, 59.77; H, 4.63; N, 16.08. Found: C, 59.79; H,
4.51; N, 16.21.
Methyl 2-((4-Fluorophenyl)(1H-1,2,4-triazol-1-yl)methyl)acrylate (4a)
1
Oil; IR (KBr) nmax: 3120, 2949, 1720, 1654 cmꢁ1; H NMR (400 MHz,
CDCl3): 8.03 (s, 1H), 8.01 (s, 1H), 7.30–7.27 (m, 2H), 7.10 (d, 1H,
J ¼ 8.4 Hz), 7.08 (d, 1H, J ¼ 8.4 Hz), 6.62 (s, 1H), 6.59 (s, 1H), 5.43 (s,
1H), 3.74 (s, 3H); 13C NMR (100 MHz, CDCl3) d 166.3, 162.4 (d,
1JC,F ¼ 238.4 Hz), 151.7, 144.7, 138.1, 131.4, 129.6, 129.5, 128.8, 115.7,
115.5, 62.1, 51.9; MS m=z (%): 261 (Mþ, 28), 229 (100), 201 (47), 133
(85). HRMS (ESI) calcd. for C13H12FN3O2 (M þ H)þ, 262.0994; found:
(M þ H)þ, 262.0999.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(3-nitrophenyl)
acrylate (3b)
Light yellow crystal, mp 141.7–142.0 ꢀC. IR (KBr) nmax: 3137, 2949,
1
1707 cmꢁ1; H NMR (400 MHz, CDCl3): dH 8.64 (s, 1H), 8.27 (m, 3H),

(E)-1,2,4-Triazole-Substituted Alkenes
3297
8.06 (s, 1H), 7.99 (s, 1H), 7.69 (m, 1H), 5.17 (s, 2H), 4.29 (q, 2H,
J ¼ 7.2 Hz), 1.34 (t, 3H, J ¼ 7.2 Hz); 13C NMR (100 MHz, CDCl3) d:
165.5, 151.8, 148.4, 144.4, 141.9, 135.4, 135.1, 129.9, 128.1, 124.3,
124.1, 61.8, 45.5, 14.0; MS m=z (%): 288 (Mþ, 15), 229 (100), 161 (20),
115 (28). Anal. calcd. for C13H12N4O4: C, 54.17; H, 4.20; N, 19.44.
Found: C, 54.05; H, 4.27; N, 19.36.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-phenylacrylate (3c)
Yellow oil.[4d] IR (neat) nmax: 3117, 2952, 1712 cmꢁ1. 1H NMR (400 MHz,
CDCl3): dH 8.26 (s, 1H), 8.07 (s, 1H), 7.98 (s, 1H), 7.72 (s, 1H), 7.70 (s,
1H) 7.46 (m, 3H), 5.20 (s, 2H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3)
d: 166.5, 151.4, 145.0, 143.8, 133.4, 129.5, 129.2, 128.5, 124.8, 52.1, 45.7;
MS m=z (%): 244 (Mþ þ H, 34), 175 (100), 143 (10), 115 (16). HRMS
(ESI) calcd. for C13H13N3O2: (M þ H)þ, 244.1088; found: (M þ H)þ,
244.1083.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(2-chlorophenyl)
acrylate (3d)
Colorless crystal, mp 99.8–100.9 ꢀC; IR (KBr) nmax: 3133, 2941, 1725; 1H
NMR (400 MHz, CDCl3): dH 8.23 (s, 1H), 8.12 (s, 1H), 8.02 (m, 1H), 7.95
(s, 1H), 7.47 (m, 1H), 7.37 (m, 2H), 5.08 (s, 2H), 3.82 (s, 3H); 13C NMR
(100 MHz, CDCl3) d: 166.1, 151.6, 144.1, 141.9, 134.0, 132.2, 130.6,
130.5, 129.5, 127.0, 126.9, 52.4, 45.9; MS m=z (%): 278 (Mþ þ H, 14),
242 (100). Anal. calcd. for C13H12ClN3O2: C, 56.22; H, 4.36; N, 15.13.
Found: C, 56.15; H, 4.47; N, 15.01.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(2-chloro-6-
fluorophenyl) acrylate (3e)
1
Yellow oil. IR (neat) nmax: 3142, 2958, 1723 cmꢁ1; H NMR (400 MHz,
CDCl3): dH 8.11 (s, 1H), 7.83 (s, 1H), 7.68 (s, 1H), 7.63 (s, 1H), 6.90
(d, 1H, J ¼ 3.6 Hz), 6.55 (m, 1H), 5.52 (s, 2H), 3.81 (s, 3H); 13C NMR
(100 MHz, CDCl3) d: 165.0, 158.5 (d, 1JC,F ¼ 220.6 Hz),
150.8, 144.4, 133.8, 133.3, 131.8, 131.2, 125.6, 120.9, 114.9, 52.4,
46.0; MS m=z (%): 296 (Mþ þ H, 12), 298 (5), 260 (100). HRMS
(ESI) calcd. for C13H11ClFN3O2: (M þ H)þ, 295.0604; found:
(M þ H)þ, 295.0606.

3298
W. Zhong et al.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(furan-2-yl)acrylate (3f)
1
Yellow oil. IR (neat) nmax: 3131, 2938, 1697 cmꢁ1; H NMR (400 MHz,
CDCl3): dH 8.18 (s, 1H), 7.91 (s, 1H), 7.68 (s, 1H), 7.64 (s, 1H), 6.91
(d, 1H, J ¼ 3.6 Hz), 6.56 (m, 1H), 5.54 (s, 2H), 3.81 (s, 3H); 13C NMR
(100 MHz, CDCl3) d: 167.1, 151.3, 149.9, 146.2, 143.2, 130.3, 120.0,
119.3, 112.6, 52.45, 46.12; MS m=z (%): 234 (Mþ þ H, 100), 165 (46).
HRMS (ESI) calcd. for C11H11N3O3: (M þ H)þ, 233.0880; found:
(M þ H)þ, 233.0878.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(4-methylthiazol-5-yl)
acrylate (3g)
Colorless crystal, mp 137.0–138.3 ꢀC; IR (KBr) nmax: 3100, 2953,
1
1705 cmꢁ1; H NMR (400 MHz, CDCl3): dH 8.88 (s, 1H), 8.19 (s, 2H),
7.92 (s, 1H), 5.35 (s, 2H), 3.84 (s, 3H), 2.65 (s, 3H); 13C NMR (100 MHz,
MHz, CDCl3) d: 166.4, 158.8, 154.7, 151.8, 143.3, 133.9, 124.1, 122.2,
52.5, 45.7, 16.0; MS m=z (%): 264 (Mþ, 14), 195 (72), 136 (100). Anal.
calcd. for C11H12N4O2S: C, 49.99; H, 4.58; N, 21.20. Found: C, 49.86;
H, 4.47; N, 21.42.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-phenylacrylate (3h)
1
Yellow oil. IR (neat) nmax: 3117, 2978, 1704 cmꢁ1; H NMR (400 MHz,
CDCl3): dH 8.25 (s, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.70 (s, 1H), 7.71
(s, 1H), 7.43 (m, 3H), 5.19 (s, 2H), 4.26 (q, 2H, J ¼ 7.2 Hz), 1.30 (t, 3H,
J ¼ 7.2 Hz); 13C NMR (100 MHz, CDCl3) d: 166.2, 151.5, 145.0, 143.9,
133.6, 129.6, 129.3, 128.7, 125.3, 61.2, 45.9, 13.9; MS m=z (%): 258.0
(Mþ þ H, 45), 188.9 (100). HRMS (ESI) calcd. for C14H15N3O2:
(M þ H)þ, 258.1244; found: (M þ H)þ, 258.1247.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-
(3-nitrophenyl)acrylate (3i)
Yellow crystal, mp 143.0–143.9 ꢀC; IR (KBr) nmax: 3121, 2978, 1702 cmꢁ1.
1H NMR (400 MHz, CDCl3): dH 8.64 (s, 1H), 8.27 (m, 3H), 8.06 (s, 1H),
7.99 (s, 1H), 7.68 (t, 1H, J¼ 7.6 Hz), 5.14 (s, 1H) 4.29 (q, 2H, J¼ 7.2 Hz),
1.34 (t, 3H, J¼ 7.2 Hz); 13C NMR (100 MHz, CDCl3) d: 164.8, 160.2,
157.7, 150.8, 143.2, 134.9, 134.4, 130.9, 125.5, 121.3, 114.4, 61.6, 46.8, 13.9;
MS m=z (%): 302 (Mþ, 15), 229 (100), 161 (50), 115 (20). Anal. calcd. for
C14H14N4O4: C, 55.63; H, 4.67; N, 18.53. Found: C, 55.59; H, 4.61; N, 18.65.

(E)-1,2,4-Triazole-Substituted Alkenes
3299
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(4-fluorophenyl)
acrylate (3j)
Colorless crystal, mp 101.2–101.9 ꢀC; IR (KBr) nmax: 3137, 2974,
1
1693 cmꢁ1. H NMR (400 MHz, CDCl3): d 8.27 (s, 1H), 8.01 (s, 1H),
7.97 (s, 1H), 7.78 (dd, 2H, J1 ¼ 5.2 Hz, J2 ¼ 8.8 Hz), 7.15 (dd, 2H,
J1 ¼ J2 ¼ 8.8 Hz), 5.17 (s, 2H), 4.26 (q, 2H, J ¼ 7.2 Hz), 1.32 (t, 3H,
J ¼ 7.2 Hz); 13C NMR (100 MHz, CDCl3) d: 166.2, 164.4 (d,
1JC,F ¼ 250 Hz), 151.7, 144.2, 143.9, 131.7, 131.6, 129.2, 125.2, 116.1,
115.9, 61.5, 45.9 and 14.0; MS m=z (%): 276.1 (Mþ þ H, 100). Anal.
calcd. for C14H14FN3O2: C, 61.08; H, 5.13; N, 15.26. Found: C, 60.99;
H, 5.26; N, 15.21.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(2-chlorophenyl)
acrylate (3k)
White solid, mp 81.3–83.0 ꢀC; IR (KBr) nmax: 3145, 2978, 1703 cmꢁ1;
1H NMR (400 MHz, CDCl3): dH 8.22 (s, 1H), 8.11 (s, 1H), 7.99 (m,
1H), 7.94 (s, 1H), 7.46 (m, 1H), 7.37 (m, 2H), 5.07 (s, 2H), 4.28 (d, 2H,
J ¼ 7.2 Hz), 1.31 (t, 3H, J ¼ 7.2 Hz). 13C NMR (100 MHz, CDCl3) d:
165.8, 151.8, 148.3, 141.9, 135.3, 134.3, 132.5, 130.7, 130.7, 129.7,
127.5, 61.6, 46.2, 14.1; MS m=z (%): 292.2 (Mþ þ H, 82), 294.2 (25).
Anal. calcd. for C14H14ClN3O2: C, 57.64; H, 4.84; N, 14.40. Found: C,
57.68; H, 4.71; N, 14.52.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(2-chloro-6-fluorophenyl)
acrylate (3l)
1
Yellow oil, IR (neat) nmax: 3138, 2952, 1719 cmꢁ1; H NMR (400 MHz,
CDCl3): dH 8.20 (s, 1H), 7.86 (s, 1H), 7.75 (s, 1H), 7.35 (m, 2H), 7.09
(m, 1H), 5.03 (s, 2H), 4.26 (q, 2H, J ¼ 7.2 Hz), 1.27 (t, 3H,
J ¼ 7.2 Hz). 13C NMR (100 MHz, CDCl3) d: 164.7, 159.9 (d,
1JC,F ¼ 248.7 Hz), 150.8, 143.21, 134.9, 134.5, 130.9, 130.8, 125.5, 121.2
2
2
(d, JC,F ¼ 189 Hz), 114.3 (d, JC,F ¼ 227 Hz), 61.6, 46.8, 13.9; MS m=z
(%): 310 (Mþ þ H, 100), 312 (31), 311 (17). HRMS (ESI) calcd. for
C14H13ClFN3O2: (M þ H)þ, 310.0760; found: (M þ H)þ, 310.0764.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(furan-2-yl)acrylate (3m)
Colorless crystal, mp 99.1–100.4 ꢀC. IR (KBr) nmax: 3121, 2986,
1
1692 cmꢁ1; H NMR (400 MHz, CDCl3): dH 8.18 (s, 1H), 7.92 (s, 1H),

3300
W. Zhong et al.
7.68 (s, 1H), 7.62 (s, 1H), 6.91 (d, 1H, J ¼ 3.6 Hz), 6.56 (dd, 1H,
J1 ¼ 3.6 Hz, J2 ¼ 2 Hz), 5.53 (s, 2H), 4.26 (q, 2H, J ¼ 7.2 Hz), 1.30 (t,
3H, J ¼ 7.2 Hz); 13C NMR (100 MHz, CDCl3) d: 166.5, 151.5, 149.8,
146.0, 143.2, 129.9, 120.4, 118.9, 112.5, 61.3, 45.9, 14.0; MS m=z (%):
248 (Mþ þ H, 100), 179 (34). Anal. calcd. for C12H13N3O3: C, 58.29;
H, 5.30; N, 16.99. Found: C, 58.41; H, 5.23; N, 17.10.
(E)-Ethyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-3-(4-methylthiazol-5-yl)
acrylate (3n)
1
Yellow oil. IR (neat) nmax: 3113, 2982, 1704 cmꢀ1; H NMR (400 MHz,
CDCl3): dH 8.88 (s, 1H), 8.20 (m, 2H), 7.94 (s, 1H), 5.36 (s, 2H), 4.30
(q, 2H, J ¼ 7.2 Hz), 2.65 (s, 3H), 1.33 (t, 3H, J ¼ 7.2 Hz); 13C NMR
(100 MHz, CDCl3) d: 165.6, 158.3, 154.5, 151.3, 143.1, 133.9, 122.3,
61.3, 45.4, 15.7, 13.7; MS m=z (%): 278 (Mþ, 35), 136 (100). HRMS
(ESI) calcd. for C12H14N4O2S: (M þ H)þ, 279.0917; found: (M þ H)þ,
279.0913.
(E)-Methyl 2-((1H-1,2,4-Triazol-1-yl)methyl)-5-methylhex-2-enoate (3o)
Colorless oil. IR (neat) nmax: 3106, 2992, 1710 cmꢀ1; 1H NMR (400 MHz,
CDCl3): dH 8.17 (s, 1H), 7.89 (s, 1H), 7.18 (t, 1H, J ¼ 7.5 Hz), 5.06 (s,
2H), 3.76 (s, 3H), 2.38 (t, 2H, J ¼ 7.5 Hz), 1.84 (m, 1H), 0.971 (d, 6H,
J ¼ 7 Hz); 13C NMR (100 MHz, CDCl3) d: 166.5, 151.5, 149.2, 143.4,
126.3, 52.2, 44.8, 37.8, 28.2, 22.4, 22.4; MS m=z (%): 223 (Mþ, 5), 167
(100). HRMS (ESI) calcd. for C11H17N3O2: (M þ H)þ, 224.1401; found:
(M þ H)þ, 224.1404.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(Nos. 20476098 and 20676123) for financial support.
REFERENCES
1. Baylis, A. B.; Hillman, M. E. D. Verfahren zur Herstellung von Acrylver-
bindungen. German Patent 21155113. Chem. Abstr. 1972, 77, 34174. 10
May 1972.
2. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Recent advances in the
Baylis–Hillman reaction and applications. Chem. Rev. 2003, 103, 811–891;
(b) Basavaiah, D.; Rao, P. D.; Hyma, R. S. The Baylis–Hillman reaction: A
novel carbon–carbon bond forming reaction. Tetrahedron 1996, 52, 8001–8062.

(E)-1,2,4-Triazole-Substituted Alkenes
3301
3. Ciganek, E. Organic Reactions; John Wiley & Sons: New York, 1997; Vol. 51,
p. 201.
4. (a) Lee, H. S.; Kim, J. M.; Kim, J. N. Synthesis of poly-substituted pyrroles
starting from the Baylis–Hillman adducts. Tetrahedron Lett. 2007, 48, 4119–
4122; (b) Kim, S. J.; Lee, H. S.; Kim, J. N. Synthesis of 3,5,6-trisubstituted
a-pyrones from Baylis–Hillman adducts. Tetrahedron Lett. 2007, 48,
1069–1072; (c) Kabalka, G. W.; Venkataiah, B.; Dong, G. Pd-catalyzed
cross-coupling of Baylis–Hillman acetates with bis(pinacolato)diboron: An
efficient route to functionalized allyl borates. J. Org. Chem. 2004, 69,
5807–5809; (d) Gong, J. H.; Kim, H. R.; Ryu, H. R.; Kim, Y. N. The reaction
of heterocyclic nucleophilies and DABCO salts of the Baylis–Hillman
acetates. Bull. Korean Chem. Soc. 2002, 23, 789–790; (e) Im, Y. J.; Na, J.
E.; Kim, J. N. One-pot synthesis of 5-arylpent-4-enoate derivatives from
Baylis–Hillman acetates: Use of phosphorous ylide. Bull. Korean Chem.
Soc. 2003, 24, 511–513.
5. (a) Liu, J. B.; Tao, W. F.; Dai, H.; Jin, Z.; Fang, J. X. Synthesis, struc-
tures, and biological activities of new 1H-1,2,4-triazole derivatives con-
taining pyridine unit. Heteroatom Chem. 2007, 18, 376–380; (b) Brandt,
C. D.; Kithcen, J. A.; Beckmann, U.; White, N. G.; Jameson, G. B.;
Brooker, S. Synthesis and structures of 3,5-disubstituted 1,2,4-triazole
head units and incorporation of 3,5-dibenzoyl-1,2,4-triazolate into new
[2 þ 2] Schiff base macrocyclic complexes. Supramolecular Chem. 2007,
19, 17–27.
6. (a) Brockunier, L. L.; Parmee, E. R.; Ok, H. O.; Candelore, M. R.;
Cascieri, M. A.; Colwell, L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.;
Hom, G. J.; MacIntyre, D. E.; Tota, L.; Wyvratt, M. J.; Fisher, M. H.;
Weber, A. E. Human b3-adrenergic receptor agonists containing 1,2,3-
triazole-substituted benzenesulfonamides. Bioorg. Med. Chem. Lett. 2000,
10, 2111–2114; (b) Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barba-
chyn, M. R.; Emmert, D. E.; Garmon, S. A.; Graber, D. R.; Grega,
K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford,
C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi,
B. H. Substituent effects on the antibacterial activity of nitrogen-carbon-
linked (azolylphenyl)oxazolidin-ones with expanded activity against the
fastidious gram-negative organisms Haemophilus influenzae and Moraxella
catarrhalis. J. Med. Chem. 2000, 43, 953–970; (c) Park, J. S.; Yu, K. A.;
Kim, S. Y.; Song, Y. J.; Kim, K. P.; Yoon, Y. S.; Han, M. R. Novel anti-
fungal triazole derivatives. PCT Int. Appl. WO2007052943, 10 May 2007;
(d) Tozkoparan, B.; Kupeli, E.; Yes¸ilada, E.; Ertan, M. Preparation of 5-
¨
aryl-3-alkylthio-l,2,4-triazoles and corresponding sulfones with antiinflam-
matory-analgesic activity. Bioorg. Med. Chem. 2007, 15, 1808–1814; (e)
Shiradkar, M.; Kumar, G. V. S.; Dasari, V.; Tatikonda, S.; Akula, K.
C.; Shah. R. Clubbed triazoles: A novel approach to antitubercular drugs.
Eur. J. Med. Chem. 2007, 42, 807–816; (f) Vlasova, L. A.; Shamaeva, E. M.;
´
Afanaseva, G. B.; Postvskii, I. Y. Synthesis of hydroxymethyl compounds
of 1,2,4-triazole and investigation of their antitumorigenic activity. Pharm.
Chem. J. 1971, 5, 473–477; (g) Labanauskas, L.; Udrenaite, E.; Gaidelis, P.;

3302
W. Zhong et al.
ꢀ
Brukstus, A. Synthesis of 5-(2-,3- and 4-methoxyphenyl)-4H-1,2,4-triazole-
3-thiol derivatives exhibiting anti-inflammatory activity. Farmaco 2004, 59,
255–259.
7. Chandrasekhar, S.; Basu, D.; Rambabu C. Three-component coupling
of alkynes, Baylis–Hillman, adducts and sodium azide: A new synthesis of
substituted triazoles. Tetrahedron Lett. 2006, 47, 3059–3063.
8. Sreedhar, B.; Reddy, P. S.; Kumar, N. S. Cu(I)-catalyzed one-pot synthesis of
1,4-disubstituted 1,2,3-triazoles via nucleophilic displacement and 1,3-dipolar
cycloaddition. Tetrahedron Lett. 2006, 47, 3055–3058.
9. For the introduction of nucleophiles at the secondary position of Baylis–
Hillman adducts by using the DABCO salt concept, see (a) Kim, J. N.;
Lee, H. J.; Lee, K. Y.; Gong, J. H. Regioselective allylic amination of the
Baylis–Hillman adducts: An easy and practical access to the Baylis–Hillman
adducts of N-tosylimines. Synlett 2002, 173–175; (b) Kim, J. M.; Lee, K. Y.;
Kim, J. N. Synthesis of 4-methylene-2-cyclohexenones and their aromatiza-
tion reaction toward para-methoxylmethyl anisole derivatives. Bull. Korean
Chem. Soc. 2004, 25, 328–330; (c) Chung, Y. M.; Gong, J. H.; Kim, T. H.;
Kim, J. N. Synthesis of ethyl 3-cyano-2-methylcinnamates and 3-cyano-2-
methylcinnamo-nitriles from the Baylis–Hillman acetates. Tetrahedron Lett.
2001, 42, 9023–9026; (d) Basavaih, D.; Kumaragurubaran, N.; Sharada,
D. S. Baylis–Hillman chemistry: A novel synthesis of functionalized
1,4-pentadienes. Tetrahedron Lett. 2001, 42, 85–87.
10. Li, J.; Wang X.; Zhang, Y. Remarkable rate acceleration of water-promoted
nucleophilic substitution of Baylis–Hillman acetate: A facile and highly
efficient synthesis of N-substituted imidazole. Tetrahedron Lett. 2005, 46,
5233–5237.
11. Bernard, A. M.; Cocco, M. T.; Congiu, C.; Franzone, G. L.; Piras, P. P.
Synthetic potentialities of alkyl and aryl cyclopropylidenealkyl sulfides:
Access to 1-(arylthio)vinvlcyclopropanes by a 1,3-shift of an arylthio group.
Synthesis 1996, 3, 361–366.