Cascade synthesis of substituted 4-amino-1,2,4-triazol-3-ones from aldehyde hydrazones and azodicarboxylates

Article abstract of DOI:10.1016/j.tet.2010.01.087

Substituted 4-amino-1,2,4-triazol-3-ones were synthesized from aldehyde hydrazones and azodicarboxylates in the presence of triphenylphosphine. The cascade reaction was conducted in a single step and the procedure is general and efficient.

Full text of DOI:10.1016/j.tet.2010.01.087

Tetrahedron 66 (2010) 2427–2432
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cascade synthesis of substituted 4-amino-1,2,4-triazol-3-ones from aldehyde
hydrazones and azodicarboxylates
,
a,
b,
a
Yehua Su a, Zhen Jiang a, Deng Hong a, Ping Lu a , Yanguang Wang
, Xianfu Lin
*
*
a Department of Chemistry, Zhejiang University, Hangzhou 310027, China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Substituted 4-amino-1,2,4-triazol-3-ones were synthesized from aldehyde hydrazones and azodi-
carboxylates in the presence of triphenylphosphine. The cascade reaction was conducted in a single step
and the procedure is general and efficient.
Received 26 November 2009
Received in revised form 22 January 2010
Accepted 26 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 1 February 2010
Keywords:
Triazolinones
Cascade reactions
Azodicarboxylates
Heterocycles
1. Introduction
2. Results and discussions
Triazolinones are an important class of organic compounds. As
pharmacophores, they possess wide biological activity such as
antitumor,1 antifungal,2 antioxidant,3 antibacterial,4 anti-in-
flammatory,5 antihistamines,6 and antiviral7 activity. Consequently,
a large amount of work has been devoted to the development of
synthetic methods for construction of triazolinones, the majority of
which involve intramolecular cyclocondensation of formyl
semicarbazides,8 intramolecular cyclocondensation of an ami-
drazone with phosgene or a phosgene surrogate,9 Mitsunobu
reaction of isocyanates and diisopropyl azodicarboxylate,10 cycli-
zation of semicarbazide11 and intramolecular cyclocondensation of
hydrazidehydrazones.12
The reaction of dialkyl azodicarboxylates and triphenylphos-
phine leading to the formation of Huisgen zwitterion,13 which
plays an important role in the Mitsunobu reaction.14 Nair and
co-workers used this zwitterion to synthesize a variety of impor-
tant compunds.15 Recently, we developed a cascade reaction of the
Huisgen zwitterions with aziridines leading to pyrazolines.16
Inspired by these works, we are interested in the reaction of
aldehyde hydrazones with Huisgen zwitterion. We herein report
the results of this effort.
Initially, we chose to focus our attention on the reaction of
benzaldehyde phenylhydrazone (1a, 1 equiv), diethyl azodi-
carboxylate (DEAD) (2a, 1 equiv), and triphenylphosphine
(1 equiv). When the reaction was performed in toluene at 110 ꢀC
for 1 h, 4-ethyl(carbethoxy)-amino-2,5-diphenyl-2H-1,2,4-triazol-
3(4H)-one (3a) was obtained with 6% yield (Table 1, entry 1). In-
trigued by this result, we carried the reaction with 2 equiv of 2a to
establish the reaction conditions (Table 1). This revealed that
treating the reaction solution of 1a (1 equiv) and 2a (2 equiv) in
toluene with triphenylphosphine (1 equiv) at 80 ꢀC for 1 h afforded
3a in best yield (Table 1, entry 6). With regards to the reaction
solvents, toluene was effective (Table 1, entries 1–8). CH3CN (Table
1, entry 12) and hexane (Table 1, entry 15) gave low yields, while
tetrahydrofuran (THF, Table 1, entry 9), dichloromethane (DCM,
Table 1, entry 10),1,2-dichloroethane (DCE, Table 1, entry 11), MeOH
(Table 1, entry 13), and dimethylformamide (DMF, Table 1, entry 14)
resulted in a complex mixture containing unknown side products
and trace product.
To define the scope of the present procedure, we next turned
our attention to the reactions of a variety of aldehyde hydrazones 1
and azodicarboxylates 2. As shown in Table 2, aromatic aldehyde
hydrazones 1a–1q could react with 2 to afford the corresponding 4-
alkyl(carbalkoxy)amino-1,2,4-triazol-3-ones 3a–3r in good to ex-
cellent yields (71–98%). The R1 group in aldehyde hydrazones 1
could be phenyl (Table 2, entries 1, 2, and 4–7), the electron-rich
(Table 2, entry 3) or the electron-deficient phenyl (Table 2, entries
* Corresponding authors. Tel./fax: þ86 571 8795 1512.
E-mail addresses: pinglu@zju.edu.cn (P. Lu), orgwyg@zju.edu.cn (Y. Wang).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.087

2428
Y. Su et al. / Tetrahedron 66 (2010) 2427–2432
Table 1
Aliphatic aldehyde hydrazones 1r–1t were also examined under
Condition screening for the reaction of 1a and 2a
the established conditions. However, we obtained products 4a (79%
yield), 4b (82% yield), and 4c (83% yield) rather than the desired
1,2,4-triazol-3-ones 3 (Scheme 1). It was also found that PPh3 was
not necessary for this transformation. When the reaction was
performed with 1 equiv of azodicarboxylates 2 under the PPh3-free
conditions, 4a, 4b, and 4c were obtained in 75%, 78%, and 82%
yields, respectively (Scheme 2). Under the same conditions, the
reaction of 1a and 2a gave an analogue 4d (Scheme 2). Treatment of
4d with trifluoroacetic acid (TFA) at room temperature afforded
diethyl 1-(phenyl(2-phenylhydrazono)-methyl) hydrazine-1,2-
dicarboxylate (5a), which was quantitatively converted to 1,2,4-
triazol-3-one 6a in the presence of TFA at 50 ꢀC (Scheme 3). In the
presence of TFA in toluene or MeOH at 50 ꢀC, 4d, 4a, and 4b could
be directly converted to 1,2,4-triazol-3-ones 6a (95% yield), 6b (94%
yield), and 6c (82% yield), respectively (Scheme 4).
Ph
N
O
N
COOEt
H
N
Ph3P
+
N
EtOOC N N
Ph
N
Ph
solvent
Ph
NEt
1a
2a
EtOOC
3a
Entry 1a/2a/Ph3P (molar ratio) Solvent Temp (ꢀC) Time (h) Yielda (%)
1
2
3
4
5
6
7
8
1:1:1
1:1:1
1:1:1
1:1:1
1:1.5:1
1:2:1
1:2.2:1.1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
1:2:1
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
THF
DCM
DCE
MeCN
MeOH
DMF
110
95
80
60
80
80
80
50
50
35
60
50
50
80
50
1
1.5
2
3.5
1.5
1
1
1
1
2
6
21
35
31
68
90
87
82
b
9
b
b
10
11
12
13
14
15
O
H
N
O
Ph3P
2
N
OR3
+
0.5
0.5
0.5
1
10
R1
N
Ph
toluene
R3O
N
b
80oC, 1 h
b
1r: R1=n-C9H19
1s: R1=i-C3H7
1t: R1=i-C3H7
2a: R3=Et
2b: R3=Bn
Hexane
25
a
Ph
N
(2 equiv)
Yield refers to 1a.
b
N
N
A complex mixture of unknown side products afforded.
R1
NH
Table 2
R3O2C
CO2R3
Synthesis of triazolinones 3 from 1 and 2a
4a: R1=n-C9H19, R3=Et; 79% yield
4b: R1=i-C3H7, R3=Et; 82% yield
4c: R1=i-C3H7, R3=Bn; 83% yield
R2
N
O
O
H
N
O
N
Ph3P
N
OR3
+
R1
N
R2
N
toluene
R3O
N
Scheme 1. Synthesis of 4a–4c in the presence of PPh3.
R1
NR3
80oC,1 h
1
R3OOC
3
2 (2equiv)
Entry
R1/R2
R3
Yieldb (%)
O
H
N
O
toluene
80oC
1
2
3
4
5
6
7
8
Ph/Ph (1a)
1a
4-MeC6H4/Ph (1b)
Ph/4-ClC6H4 (1c)
Ph/4-NO2C6H4 (1d)
Ph/4-MeOC6H4 (1e)
Ph/4-MeC6H4 (1f)
3-NO2C6H4/4-MeC6H4 (1g)
4-NO2C6H4/Ph (1h)
2-ClC6H4/Ph (1i)
4-BrC6H4/Ph (1j)
4-NO2C6H4/Ph (1k)
4-ClC6H4/4-ClC6H4 (1l)
4-NO2C6H4/4-NO2C6H4 (1m)
4-NO2C6H4/3,4-(NO2)2C6H4 (1n)
Et (2a)
Bn (2b)
2a
2a
2a
2a
2b
2a
2b
2a
2a
3a 90
3b 92
3c 84
3d 85
3e 71
3f 92
3g 92
3h 95
3i 98
3j 93
3k 90
3l 97
3m 87
3n 78
3o 58
+
R1
N
Ph
N
OR3
R3O
N
10 min
1r: R1=n-C9H19
1s: R1=i-C3H7
1t: R1=i-C3H7
1a: R1=Ph
2a: R3=Et
2b: R3=Bn
Ph
(1 equiv)
N
N
N
R1
9
NH
CO2R3
R3O2C
10
11
12
13
14
15
4a: R1=n-C9H19, R3=Et; 75% yield
4b: R1=i-C3H7, R3=Et; 78% yield
4c: R1=i-C3H7, R3=Bn; 82% yield
4d: R1=Ph, R3=Et; 98% yield
2a
2a
2a
2a
Scheme 2. Synthesis of 4a–4d in the absence of PPh3.
16
17
2a
2a
3p 82
3q 76
/Ph (1o)
O
/ Ph (1p)
Ph
H
N
N
N
N
N
N
TFA
MeOH
rt, 10 min
Ph
Ph
Ph
H
N
18
2a
3r 87
NH
CO2Et
CO2Et
EtO2C
EtO2C
N
/ Ph (1q)
4d
5a, 95% yield
a
Reaction conditions:
(15 mL), 80 ꢀC, 1 h.
1
(0.5 mmol), 2 (1 mmol), PPh3 (0.5 mmol), toluene
Ph
b
N
TFA, MeOH
50 oC, 1.5 h
Yield refers to 1.
O
N
N
Ph
8–15), naphthalenyl (Table 2, entry 16), or heterocycle (Table 2,
entries 17 and 18). When R2 is strongly electron-deficient (Table 2,
entries 5, 14, and 15), lower yields were obtained than that in the
case where R2 is electron-rich (Table 2, entries 6–8).
COOEt
N
H
6a, 97% yield
Scheme 3. Synthesis of 5a and 6a.

Y. Su et al. / Tetrahedron 66 (2010) 2427–2432
2429
Ph
NH
Ph
N
N
N
TFA, MeOH
50 oC, 1.5 h
N
R1
R1
OH
NH
CO2Et
N
NH
C
EtO2C
EtO2C
OEt
4d: R1=Ph
5
4a: R1=n-C9H19
4b: R1=i-C3H7
Ph
N
O
N
N
R1
NH
COOR3
6a: R1=Ph; 95% yield
6b: R1=n-C9H19; 94% yield
6c: R1=i-C3H7; 82% yield
Scheme 4. Synthesis of 1,2,4-triazol-3-ones 6.
The structures of products were characterized by 1H NMR, 13
C
NMR, IR, and HRMS spectra. The structure of compounds 3i, 3l
(Fig. 1), and 5a (Fig. 2) were unambiguously confirmed by X-ray
analysis (see Supplementary data).17
Figure 2. X-ray crystal structure of 5a.
PPh3
PPh
N
O
3O
PPh3
N N C
O
O
O
O
EtO
C
C
N N C
N
OEt
OEt
EtO
H
OEt
R1
EtO
A
N
R2
(DEAD)
N
H
B
N
R2
N
1
R1
Ph3
P
PPh
3O
N
OEt
R1
EtO
PPh
N
3O
O
O
O
N
EtO
R2
O
N
O
N
N
OEt
N
OEt
R1
R2
R1
N
N
R2
N
N
N
H
H
H
E
D
C
Ph3PO
O
O
N
O
N
O
N
OEt
R1
N
O
OEt
R1
O
N
R2
N
Figure 1. X-ray crystal structure of 3l.
N
N
R2
N
N
H
OEt
H
G
H
R1
N
On the bases of these results, we proposed a possible mecha-
nism for the formation of 4-alkyl(carbalkoxy)-amino-1,2,4-triazol-
3-ones 3 (Scheme 5). Firstly, the reaction of triphenylphosphine
with DEAD leads to Huisgen zwitterions A.13 A nucleophilically
attacks the carbon atom of C]N in hydrazone 1 to give B, which
isomerizes to C in turn. The nitrogen anion in C nucleophilically
attacks the carboxylic carbon and further cyclizes to form E. E
subsequently releases Ph3PO, following by an intramolecular nu-
cleophilic substitution, to form intermediate G. Nucleophilical ad-
dition of G to another DEAD, following by proton exchange and
elimination of 2H-DEAD, yields the dehydrogenated product 3.
Regarding to formation of B and D, the substrates bearing an
electron-deficient R1 and/or an electron-rich R2 (Table 2, entries 8,
9, and 12) should be reactive than that bearing an electron-rich R1
and/or an electron-deficient R2 (Table 2, entries 5, 14, and 15).
The formation of 5 (R1¼aryl) from hydrazones 1 (R1¼aryl) and
azodicarboxylates 2 has been reported by Gillis and Daniher.12 The
reaction firstly yielded 4 (R1¼aryl) via acyclic mechanism,12,18 which
subsequently isomerized to more stable 5 (R1¼aryl). The resulting 5
(R1¼aryl) could easily cyclize to 1,2,4-triazol-3-ones 6 (R1¼aryl).12
R2
N
N
N
O
O
H
CO2Et
EtO2C
C
N N C
F
H
OEt
EtO
(DEAD)
O
N
N
O
O
OEt
R1
N
O
N
OEt
N
R2
N
R1
N
R2
3
N
H
+
N
NH
CO2Et
EtO2CNHNHCO2Et
(2H-DEAD)
EtO2C
I
Scheme 5. A plausible mechanism for the synthesis of 1,2,4-triazol-3-ones 3.
In our reaction system containing PPh3, there are two compet-
itive reactions. The first one is the reaction between hydrazones 1
and Huisgen zwitterions A, and the second one is the formation of
4. We obtained 3 as the major product when R1¼aryl. It is probably
because the presence of the aromatic group increases the acidity of

2430
Y. Su et al. / Tetrahedron 66 (2010) 2427–2432
proton, which facilitates the deprotonation and aromatization. So
the electron-deficient R1 may help to obtain the desired products 3
(see Table 2, entries 8, 9, and 12). Whereas, when R1¼alkyl, the
second reaction leading to 4 is quicker than the first one.
4.2.2.3. 4-Ethyl(carbethoxy)amino-2-phenyl-5-(4-methylphenyl)-
2H-1,2,4-triazol-3(4H)-one (3c). Colorless gum; 1H NMR (500 MHz,
DMSO):
d
7.98 (m, 2H), 7.64 (d, J¼8.2 Hz, 2H), 7.51 (m, 2H), 7.39 (d,
J¼8.0 Hz, 2H), 7.30 (m, 1H), 4.20 (m, 2H), 3.72 (m, 2H), 2.40 (s, 3H),
1.17 (m, 3H), 1.07 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d
154.6, 149.6, 145.4, 141.3, 137.6, 129.7, 129.2, 127.1, 125.7, 122.3,
3. Conclusion
118.4, 63.0, 45.6, 21.0, 14.2, 12.6; HRMS (ESI) calcd for C20H22N4O3
([MþNa]þ): 389.1584, found: 389.1590; IR (KBr)
n
(cmꢁ1): 2964,
In summary, we have developed a synthesis of substituted 4-
amino-1,2,4-triazol-3-ones 3 from aldehyde hydrazones 1 and
azodicarboxylates 2 in the presence of triphenylphosphine. The
single step reaction involves a Huisgen zwitterion formation and
a subsequent domino process. The procedure is efficient and gen-
eral, and the substrates are readily available. This method will find
its applications in organic synthesis.
1739, 1597, 1502, 1459, 1263.
4.2.2.4. 4-Ethyl(carbethoxy)amino-2-(4-chlorophenyl)-5-phenyl-
2H-1,2,4-triazol-3(4H)-one (3d). White solid; mp 114–115 ꢀC; 1H
NMR (500 MHz, DMSO):
4.20 (m, 2H), 3.72 (m, 2H), 1.17 (m, 3H), 1.07 (m, 3H); 13C NMR
(125 MHz, DMSO): 154.5, 149.5, 145.6, 136.3, 131.3, 130.0, 129.2,
d 8.00 (m, 2H), 7.74 (m, 2H), 7.58 (m, 5H),
d
129.1, 127.3, 124.9, 119.9, 63.1, 45.7, 14.2, 12.6; HRMS (ESI) calcd for
C19H19ClN4O3 ([MþNa]þ): 409.1038, found: 409.1043; IR (KBr)
n
4. Experimental section
(cmꢁ1): 2990, 1740, 1716, 1597, 1496, 1460, 1270.
4.1. General considerations
4.2.2.5. 4-Ethyl(carbethoxy)amino-2-(4-nitrophenyl)-5-phenyl-
2H-1,2,4-triazol-3(4H)-one (3e). Yellow solid; mp 136–137 ꢀC; 1H
IR spectra were recorded on a FTIR spectrometer (KBr) and
reported in reciprocal centimeters (cmꢁ1). NMR spectra were
recorded for 1H NMR at 500 MHz and for 13C NMR at 125 MHz.
NMR spectra data were recorded at 75 ꢀC and were reported as
follows: chemical shift, integration, multiplicity (s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet, br¼broad), and
NMR (500 MHz, DMSO):
d
8.39 (d, J¼9.2 Hz, 2H), 8.27 (m, 2H), 7.77
(m, 2H), 7.62 (m, 3H), 4.21 (m. 2H), 3.74 (m, 2H), 1.17 (m, 3H), 1.09 (t,
J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 154.4, 149.8, 146.7,
144.6, 142.4, 131.7, 129.2, 127.5, 125.2, 124.7, 118.1, 63.2, 45.8, 14.2,
12.7; HRMS (ESI) calcd for C19H19N5O5 ([MþNa]þ): 420.1278, found:
coupling constant in hertz. For 13C NMR, TMS (
d
¼0) or CDCl3
420.1287; IR (KBr)
1280.
n
(cmꢁ1): 2988,1743,1712,1597,1519,1498,1454,
(d
¼77.25) was used as internal standard and spectra were obtained
with complete proton decoupling. High resolution mass spectral
(HRMS) data were obtained using electron spray ionization. Mp
data were measured with micro melting point apparatus. Ele-
mental analyses were recorded on an automatic analyzer.
4.2.2.6. 4-Ethyl(carbethoxy)amino-2-(4-methoxyphenyl)-5-phe-
nyl-2H-1,2,4-triazol-3(4H)-one (3f). Colorless gum; 1H NMR
(500 MHz, DMSO):
d 7.85 (m, 2H), 7.74 (m, 2H), 7.58 (m, 3H), 7.08
(m, 2H), 4.20 (m, 2H), 3.82 (s, 3H), 3.72 (m, 2H), 1.17 (m, 3H), 1.06 (t,
4.2. Preparation of 3 and 4
J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 157.6, 154.6, 149.6,
145.0, 131.1, 130.8, 129.1, 127.2, 125.3, 120.4, 114.6, 63.0, 55.6, 45.6,
4.2.1. General procedure. To a solution of 1 (0.5 mmol) and 2
(1 mmol) in anhydrous toluene (10 mL) was added a solution of
PPh3 (0.5 mmol) in anhydrous toluene (5 mL). The mixture was
stirred at 80 ꢀC for 1 h. The solvent was evaporated in vacuum and
the residue was purified by silica gel column chromatography using
hexane/EtOAc (10:1 to 6:1) as the eluent.
14.2, 12.6; HRMS (ESI) calcd for C20H22N4O4 ([MþNa]þ): 405.1533,
found: 405.1541; IR (KBr)
n
(cmꢁ1): 2980, 1738, 1514, 1453, 1249.
4.2.2.7. 4-Benzyl(carbobenzoxy)amino-2-(4-methylphenyl)-5-
phenyl-2H-1,2,4-triazol-3(4H)-one (3g). Colorless gum; 1H NMR
(500 MHz, DMSO):
d 7.99 (m, 2H), 7.49 (m, 1H), 7.33 (m, 11H), 7.18
(m, 1H), 7.09 (m, 4H), 5.31 (m, 2H), 5.03 (d, J¼14.3 Hz, 1H), 4.69
4.2.2. General procedure for the synthesis of 4 in the absence of
PPh3. The solution of 1 (0.5 mmol) and 2 (0.5 mmol) in anhydrous
toluene (10 mL) was stirred at 80 ꢀC for 10 min. The solvent was
evaporated in vacuum and the residue was purified by silica gel
column chromatography using hexane/EtOAc (6:1) as the eluent.
(d, J¼14.3 Hz, 1H), 2.35 (s, 3H); 13C NMR (125 MHz, DMSO):
d
154.9, 149.1, 145.2, 135.6, 135.3, 135.0, 133.8, 130.8, 129.6, 129.5,
128.6, 128.5, 128.3, 128.2, 128.1, 127.7, 127.2, 124.8, 118.6, 68.6,
53.9, 20.5; HRMS (ESI) calcd for C30H26N4O3 ([MþNa]þ): 513.1897,
found: 513.1899; IR (KBr)
1261.
n
(cmꢁ1): 2963, 1738, 1514, 1497, 1453,
4.2.2.1. 4-Ethyl(carbethoxy)amino-2,5-diphenyl-2H-1,2,4-triazol-
3(4H)-one (3a). Colorless gum; 1H NMR (500 MHz, DMSO):
d
7.99
4.2.2.8. 4-Ethyl(carbethoxy)amino-2-(4-methylphenyl)-5-(3-ni-
(m, 2H), 7.75 (m, 2H), 7.60 (m, 3H), 7.50 (m, 2H), 7.31 (m, 1H), 4.20
trophenyl)-2H-1,2,4-triazol-3(4H)-one (3h). White solid; mp 131–
(m, 2H), 3.73 (m, 2H), 1.17 (m, 3H), 1.07 (t, J¼7.2 Hz, 3H); 13C NMR
132 ꢀC; 1H NMR (500 MHz, DMSO):
d
8.51 (s, 1H), 8.41 (d, J¼7.6 Hz,
(125 MHz, DMSO):
d
154.6, 149.7, 145.4, 137.5, 131.2, 129.2, 129.1,
1H), 8.18 (d, J¼7.8 Hz, 1H), 7.89 (t, J¼8.0 Hz, 1H), 7.84 (d, J¼8.2 Hz,
2H), 7.32 (d, J¼8.2 Hz, 2H), 4.22 (m. 2H), 3.77 (m, 2H), 2.35 (s, 3H),
1.18 (m, 3H), 1.10 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
127.3, 125.8, 125.2, 118.4, 63.1, 45.6, 14.2, 12.6; HRMS (ESI) calcd for
C19H20N4O3 ([MþNa]þ): 375.1428, found: 375.1442; IR (KBr)
n
(cmꢁ1): 2981, 1732, 1597, 1496, 1455, 1268.
d 154.6, 149.4, 148.4, 143.2, 135.6, 134.9, 133.2, 131.1, 129.6, 126.6,
125.6, 121.7, 118.6, 63.3, 45.8, 20.5, 14.2, 12.7; HRMS (ESI) calcd for
4.2.2.2. 4-Benzyl(carbobenzoxy)amino-2,5-diphenyl-2H-1,2,4-tri-
C20H21N5O5 ([MþNa]þ): 434.1435, found: 434.1445; IR (KBr)
n
azol-3(4H)-one (3b). Colorless gum; 1H NMR (500 MHz, DMSO):
(cmꢁ1): 2986, 1742, 1535,1513, 1267.
d
7.91 (m, 2H), 7.50 (m, 3H), 7.31 (m, 10H), 7.16 (m, 1H), 7.09 (m, 4H),
5.30 (m, 2H), 5.02 (d, J¼14.2 Hz, 1H), 4.69 (d, J¼14.2 Hz, 1H); 13C
4.2.2.9. 4-Benzyl(carbobenzoxy)amino-5-(4-nitrophenyl)-2-phe-
nyl-2H-1,2,4-triazol-3(4H)-one (3i). Pale brown solid; mp 137–
NMR (125 MHz, DMSO):
d
154.9, 149.2, 145.4, 137.4, 135.6, 133.8,
130.9, 129.5, 129.2, 128.6, 128.5, 128.3, 128.2, 128.1, 127.8, 127.3,
125.9, 154.8, 118.5, 68.7, 53.9; HRMS (ESI) calcd for C29H24N4O3
138 ꢀC; 1H NMR (500 MHz, DMSO):
d
8.11 (d, J¼8.8 Hz, 2H), 7.91 (d,
J¼7.9 Hz, 2H), 7.53 (m, 4H), 7.32 (m, 6H), 7.10 (m, 5H), 5.34 (m. 2H),
([MþNa]þ): 499.1741, found: 499.1752; IR (KBr)
n
(cmꢁ1): 3064,
5.15 (d, J¼14.2 Hz, 1H), 4.65 (d, J¼14.2 Hz, 1H); 13C NMR (125 MHz,
3034, 2958, 1732, 1597, 1496, 1455, 1219.
DMSO): d 154.8, 149.0, 148.7, 143.6, 137.1, 135.5, 133.7, 130.4, 129.7,

Y. Su et al. / Tetrahedron 66 (2010) 2427–2432
2431
129.3, 128.5, 128.4, 128.3, 128.2, 128.0, 126.3, 123.7, 118.7, 68.9,
4.2.2.16. 4-Ethyl(carbethoxy)amino-5-(naphthalen-2-yl)-2-phe-
53.8; HRMS (ESI) calcd for C29H23N5O5 ([MþNa]þ): 544.1591,
nyl-2H-1,2,4-triazol-3(4H)-one (3p). Colorless gum; 1H NMR
found: 544.1599; IR (KBr)
1301.
n
(cmꢁ1): 3064, 1731, 1599, 1518, 1448,
(500 MHz, DMSO):
d
8.31 (s,1H), 8.10 (d, J¼8.6 Hz,1H), 8.03 (m, 4H),
7.87 (m, 1H), 7.65 (m, 2H), 7.53 (m, 2H), 7.31 (m, 1H), 4.23 (m, 2H),
3.79 (m, 2H), 1.18 (m, 3H), 1.11 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz,
4.2.2.10. 4-Ethyl(carbethoxy)amino-5-(2-chlorophenyl)-2-phe-
DMSO): d 154.6, 149.8, 145.3, 137.6, 133.9, 132.5, 129.2, 128.9, 128.7,
nyl-2H-1,2,4-triazol-3(4H)-one (3j). Colorless gum; 1H NMR
128.0, 127.8, 127.4, 127.2, 125.9, 123.7, 122.5, 118.5, 63.1, 45.8, 14.2,
(500 MHz, DMSO):
d
7.94 (m, 2H), 7.70 (m, 2H), 7.56 (m, 4H), 7.32
12.6; HRMS (ESI) calcd for C23H22N4O3 ([MþNa]þ): 425.1584,
(m, 1H), 4.17 (q, J¼7.0 Hz, 2H), 4.36 (m, 2H), 1.19 (t, J¼7.0 Hz, 3H),
found: 425.1588; IR (KBr)
1266.
n
(cmꢁ1): 3061, 2979, 1732, 1598, 1501,
1.05 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 154.3, 149.3,
144.2, 137.4, 133.6, 133.2, 132.0, 130.3, 129.3, 127.6, 126.0, 124.2,
128.5, 63.1, 45.9, 40.1, 12.7; HRMS (ESI) calcd for C19H19ClN4O3
4.2.2.17. 4-Ethyl(carbethoxy)amino-5-(furan-2-yl)-2-phenyl-2H-
([MþNa]þ): 409.1038, found: 409.1044; IR (KBr)
n
(cmꢁ1): 2981,
1,2,4-triazol-3(4H)-one (3q). Colorless liquid; 1H NMR (500 MHz,
1739, 1598, 1502, 1460, 1269.
DMSO):
(m, 1H), 4.17 (m, 2H), 3.86 (m, 1H), 3.73 (m, 1H), 1.17 (m, 6H); 13C
NMR (125 MHz, DMSO): 154.2, 149.2, 146.1, 139.2, 138.3, 137.4,
d 7.93 (m, 3H), 7.50 (m, 2H), 7.73 (m, 1H), 7.03 (m, 1H), 6.73
4.2.2.11. 4-Ethyl(carbethoxy)amino-5-(4-bromophenyl)-2-phe-
d
nyl-2H-1,2,4-triazol-3(4H)-one (3k). Colorless gum; 1H NMR
129.2, 125.9, 118.4, 113.1, 112.2, 62.9, 45.3, 14.2, 12.5; HRMS (ESI)
(500 MHz, DMSO):
d
7.97 (d, J¼7.8 Hz, 2H), 7.80 (d, J¼8.6 Hz, 2H),
calcd for C17H18N4O4 ([MþNa]þ): 365.1220, found: 365.1219; IR
7.70 (d, J¼8.5 Hz, 2H), 7.52 (m, 2H), 7.31 (m, 1H), 4.20 (m, 2H), 3.74
(KBr) n
(cmꢁ1): 2982, 1740, 1597, 1503, 1460, 1270.
(m, 2H), 1.17 (m, 3H), 1.09 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz,
DMSO):
d
157.4, 152.5, 147.4, 140.3, 135.2, 132.1, 132.0, 128.8, 127.9,
4.2.2.18. 4-Ethyl(carbethoxy)amino-5-(pyridin-4-yl)-2-phenyl-
127.2, 121.4, 66.1, 48.6, 17.1, 15.5; HRMS (ESI) calcd for C19H19BrN4O3
2H-1,2,4-triazol-3(4H)-one (3r). Colorless liquid; 1H NMR
([MþNa]þ): 453.0533, found: 453.0536; IR (KBr)
n
(cmꢁ1): 2980,
(500 MHz, DMSO): d 8.82 (m, 2H), 7.98 (m, 2H), 7.72 (m, 2H), 7.53
1741, 1598, 1491, 1460, 1267.
(m, 2H), 7.34 (m, 1H), 4.21 (m, 2H), 3.77 (m, 2H), 1.17 (m, 3H), 1.13 (t,
J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 154.5, 150.8, 149.6,
143.2, 137.3, 132.4, 129.3, 126.3, 120.7, 118.7, 63.3, 45.7, 14.2, 12.6;
4.2.2.12. 4-Ethyl(carbethoxy)amino-5-(4-nitrophenyl)-2-phenyl-
2H-1,2,4-triazol-3(4H)-one (3l). Pale yellow solid; mp 115–117 ꢀC;
HRMS (ESI) Calcd for C18H19N5O3 ([MþNa]þ): 376.1380, found:
1H NMR (500 MHz, DMSO):
d
8.40 (d, J¼8.6 Hz, 2H), 8.05 (d,
376.1390; IR (KBr) n
(cmꢁ1): 2981, 1740, 1597, 1499, 1446, 1268.
J¼8.6 Hz, 2H), 7.98 (d, J¼8.2 Hz, 2H), 7.53 (m, 2H), 7.32 (m, 1H),
4.21 (m. 2H), 3.78 (q, J¼7.2 Hz, 2H), 1.17 (m, 3H), 1.12 (t, J¼7.2 Hz,
4.2.2.19. Diethyl 1-(1-(phenyldiazenyl)decyl)hydrazine-1,2-dicarbo-
3H); 13C NMR (125 MHz, DMSO):
d
154.5, 149.5, 149.1, 143.5,
xylate (4a). Pale yellow solid; mp 58–59 ꢀC; 1H NMR (500 MHz,
137.3, 130.8, 129.3, 128.5, 126.2, 124.3, 118.6, 63.3, 45.7, 14.2, 12.6;
DMSO): d 9.06 (br, 1H), 7.66 (m, 2H), 7.52 (m, 3H), 5.56 (s, 1H), 4.09
(m, 4H), 1.92 (m, 1H), 1.80 (m, 1H), 1.49 (m, 2H), 1.26 (m, 18H), 0.86
HRMS (ESI) calcd for C19H19N5O5 ([MþNa]þ): 420.1278, found:
420.1283; IR (KBr)
1269.
n
(cmꢁ1): 2989, 1744, 1719, 1597, 1519, 1460,
(t, J¼7.0 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 156.5, 155.7, 151.5,
131.0, 129.1, 122.3, 86.0, 61.9, 60.8, 31.3, 29.6, 28.9, 28.8, 28.7, 28.6,
24.5, 22.0, 14.4, 14.3, 13.8; HRMS (ESI) calcd for C22H36N4O4
4.2.2.13. 4-Ethyl(carbethoxy)amino-5-(4-chlorophenyl)-2-(4-
([MþNa]þ): 443.2629, found: 443.2639; IR (KBr)
n
(cmꢁ1): 3293,
chlorophenyl)-2H-1,2,4-triazol-3(4H)-one (3m). White solid; mp
2922, 1755, 1684, 1502, 1468, 1418, 1228.
124–125 ꢀC; 1H NMR (500 MHz, DMSO):
d 8.00 (m, 2H), 7.77 (d,
J¼8.6 Hz, 2H), 7.66 (d, J¼6.8 Hz, 2H), 7.56 (m, 2H), 4.20 (m. 2H), 3.74
4.2.2.20. Diethyl 1-(2-methyl-1-(phenyldiazenyl)propyl)hydrazine-
(m, 2H), 1.16 (m, 3H), 1.08 (t, J¼7.2 Hz, 3H); 13C NMR (125 MHz,
1,2-dicarboxylate (4b). Pale yellow solid; mp 82–83 ꢀC; 1H NMR
DMSO):
d
154.8, 149.8, 145.0, 136.8, 136.6, 130.4, 129.8, 129.6, 129.4,
(500 MHz, DMSO): d 9.10 (br, 1H), 7.68 (m, 2H), 7.52 (m, 3H), 5.15 (d,
124.1, 120.2, 63.6, 46.0, 14.6, 13.0; HRMS (ESI) calcd for
J¼7.7 Hz, 1H), 4.09 (q, J¼7.0 Hz, 4H), 2.49 (m, 1H), 1.14 (m, 9H), 0.83
C19H18Cl2N4O3 ([MþNa]þ): 443.0648, found: 443.0649; IR (KBr)
n
(d, J¼6.0 Hz, 3H); 13C NMR (125 MHz, DMSO):
d 156.4, 155.8, 151.6,
(cmꢁ1): 2996, 1742, 1716, 1597, 1493, 1445, 1271.
131.0, 129.1, 122.3, 91.3, 61.9, 60.8, 28.7, 19.2, 18.3, 14.4, 14.3; HRMS
(ESI) calcd for C16H24N4O4 ([MþNa]þ): 359.1690, found: 359.1691; IR
4.2.2.14. 4-Ethyl(carbethoxy)amino-5-(4-nitrophenyl)-2-(4-ni-
(KBr) n
(cmꢁ1): 3293, 2981, 2936, 1753, 1683, 1528, 1497, 1417, 1223.
trophenyl)-2H-1,2,4-triazol-3(4H)-one (3n). Pale yellow solid; mp
174–176 ꢀC; 1H NMR (500 MHz, DMSO):
d
8.43 (m, 4H), 8.28 (m,
4.2.2.21. Dibenzyl 1-(2-methyl-1-(phenyldiazenyl)propyl)hydrazine-
2H), 8.07 (m, 2H), 4.25 (m, 2H), 3.80 (m, 2H), 1.18 (m, 3H), 1.13
1,2-dicarboxylate (4c). Pale yellow solid; mp 93–94 ꢀC; 1H NMR
(t, J¼7.2 Hz, 3H); 13C NMR (125 MHz, DMSO):
d
154.4, 149.6,
(500 MHz, DMSO) d 9.45 (br,1H), 7.63 (m, 2H), 7.48 (m, 3H), 7.29 (m,
149.4, 144.8, 142.1, 130.3, 128.2, 125.2, 124.4, 118.4, 63.5, 45.8,
10H), 5.20 (s, 1H), 5.12 (m, 4H), 2.51 (m, 1H), 1.10 (d, J¼5.0 Hz, 3H),
14.2, 12.7; HRMS (ESI) calcd for C19H18N6O7 ([MþNa]þ):
0.82 (d, J¼5.0 Hz, 3H); 13C NMR (125 MHz, DMSO)
d 156.4, 155.7,
465.1129, found: 465.1144; IR (KBr)
1593, 1518, 1274.
n
(cmꢁ1): 2963, 1754, 1715,
151.5, 136.6, 136.3, 131.0, 129.1, 128.3, 127.9, 127.6, 127.3, 122.4, 91.5,
67.4, 66.4, 28.7, 19.2, 18.3; HRMS (ESI) calcd for C26H28N4O4
([MþNa]þ): 483.2003, found: 483.2007; IR (KBr)
n
(cmꢁ1): 3280,
4.2.2.15. 4-Ethyl(carbethoxy)amino-5-(4-nitrophenyl)-2-(2,4-di-
2962, 1744, 1689, 1499, 1411, 1221.
nitrophenyl)-2H-1,2,4-triazol-3(4H)-one (3o). Pale yellow solid; mp
132–133 ꢀC; 1H NMR (500 MHz, DMSO):
d
8.84 (d, J¼2.6 Hz, 1H),
4.2.2.22. Diethyl 1-(phenyl(phenyldiazenyl)methyl)hydrazine-1,2-
8.71 (m, 1H), 8.44 (m, 2H), 8.25 (d, J¼9.0 Hz, 1H), 8.03 (m, 2H), 4.23
dicarboxylate (4d)19. Yellow solid; mp 95–96 ꢀC; 1H NMR
(m, 2H), 3.76 (m, 2H), 1.21 (t, J¼7.0 Hz, 3H), 1.11 (t, J¼7.0 Hz, 3H);
(500 MHz, DMSO)
2H), 7.34 (m, 3H), 6.71 (s, 1H), 4.20 (m, 2H), 3.81 (m, 2H), 1.15 (m,
3H), 1.02 (m, 3H); 13C NMR (125 MHz, DMSO)
155.7, 151.4, 131.3,
d 9.16 (br, 1H), 7.75 (m, 2H), 7.55 (m, 3H), 7.43 (m,
13C NMR (125 MHz, DMSO):
d 154.2, 149.6, 149.5, 146.1, 146.0,
142.3, 132.9, 130.0, 128.8, 128.6, 127.2, 124.5, 121.4, 63.6, 45.7, 14.0,
d
12.5; HRMS (ESI) calcd for C19H17N7O9 ([MþNa]þ): 510.0980,
129.2, 128.9, 128.4, 128.1, 122.4, 87.7, 62.1, 60.5, 14.3; HRMS (ESI)
found: 510.0992; IR (KBr)
1267.
n
(cmꢁ1): 2979, 1761, 1729, 1603, 1491,
calcd for C19H22N4O4 ([MþNa]þ): 393.1533, found: 393.1523; IR
(KBr)
n
(cmꢁ1): 3294, 2982, 1756, 1683, 1498, 1416, 1314, 1225.

2432
Y. Su et al. / Tetrahedron 66 (2010) 2427–2432
4.3. Preparation of 5a and 6a
C14H18N4O3 ([MþNa]þ): 313.1271, found: 313.1263; IR (KBr)
n
(cmꢁ1): 3206, 2978, 1749, 1704, 1497, 1460, 1246.
4.3.1. General procedure. To a solution of 4d (1 mmol) in MeOH
(15 mL) was added TFA (1 mmol). The mixture was stirred at room
temperature for 10 min. The solvent was evaporated in vacuum and
residual oil was purified by silica gel column chromatography using
hexane/EtOAc (7:1) as the eluent to give pure 5a. Compound 5a
(0.5 mmol) was dissolved in MeOH (10 mL). TFA (0.5 mmol) was
added and the resulting mixture was stirred at 50 ꢀC for 1.5 h. The
solvent was evaporated in vacuum and product was purified by
silica gel column chromatography using hexane/EtOAc (5:1) as the
eluent to give pure 6a.
Acknowledgements
We thank the China National 863 project (2007AA02Z143) and
the National Natural Science Foundation of China (No. 20872128)
for financial supports of this work.
Supplementary data
Copies of 1H and 13C NMR spectra for all products. Supple-
mentary data associated with this article can be found in the online
version, at doi:10.1016/j.tet.2010.01.087.
4.3.2. General procedure for the synthesis of 6 from 4. The solution
of 4 (0.5 mmol) and TFA (0.5 mmol) in MeOH was stirred at 50 ꢀC
for 1.5 h. The solvent was evaporated in vacuum and residue was
purified by silica gel column chromatography using hexane/EtOAc
(5:1) as the eluent to afford pure 6.
References and notes
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2000, 35, 743–750.
4.3.2.1. Diethyl 1-(phenyl(2-phenylhydrazono)methyl)hydrazine-
1,2-dicarboxylate (5a). White solid; mp 123–124 ꢀC; 1H NMR
(500 MHz, DMSO):
d 9.98 (br, 2H), 7.74 (m, 2H), 7.39 (m, 2H), 7.30
(m, 3H), 7.15 (m, 2H), 6.84 (m, 1H), 4.20 (q, J¼7.0 Hz, 2H), 4.11 (m,
2H), 1.23 (t, J¼6.8 Hz, 3H), 1.00 (m, 3H); 13C NMR (125 MHz, DMSO):
d
158.3, 153.8, 144.3, 134.0, 132.7, 129.3, 128.4, 128.2, 125.5, 120.3,
6. Loev, B.; Musser, J. H.; Brown, R. E.; Jones, H.; Kahen, R.; Huang, F. C.; Khand-
wala, A.; Sonnino-Goldman, P.; Leibowitz, M. J. J. Med. Chem. 1985, 28, 363–366.
7. Witkowski, J. T.; Robins, R. K.; Khare, G. P.; Sidwell, R. W. J. Med. Chem. 1973, 16,
935–937.
113.0, 62.7, 62.1, 14.3, 14.1; HRMS (ESI) calcd for C19H22N4O4
([MþNa]þ): 393.1533, found: 393.1522; IR (KBr)
n
(cmꢁ1): 3281,
3245, 2984, 1736, 1705, 1559, 1496, 1448, 1260.
8. (a) Huang, X. H.; Palani, A.; Xiao, D.; Aslanian, R.; Shih, N.-Y. Org. Lett. 2004, 6,
4795–4798; (b) Madding, G. D.; Smith, D. W.; Sheldon, R. I.; Lee, B. J. Heterocycl.
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9. (a) Uneyamma, K.; Yamashita, F.; Sugimoto, K.; Morimoto, O. Tetrahedron Lett.
1990, 31, 2717–2718; (b) Bartsch, H.; Erker, T. J. Heterocycl. Chem. 1990, 27, 991–
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O.; Chiang, G. C. Org. Process Res. Dev. 2001, 5, 593–598; (d) Romine, J. L.; Martin,
S. W.; Gribkoff, V. K.; Boissard, C. G.; Dworetzky, S. I.; Natale, J.; Li, Y.; Gao, Q.;
Meanwell, N. A.; Starrett, J. E., Jr. J. Med. Chem. 2002, 45, 2942–2952.
10. Alizadeh, A. Helv. Chim. Acta 2005, 88, 2777–2780.
11. (a) Gruttadauria, M.; Buccheri, F.; Cusmano, G.; Meo, L. P.; Noto, R.; Werber,
G. J. Heterocycl. Chem. 1993, 30, 765–770; (b) Nguyen, T. H.; Milcent, R.;
Barbier, G. J. Heterocycl. Chem. 1985, 22, 1383–1388; (c) Milcent, R.; Nguyen,
T. H. J. Heterocycl. Chem. 1986, 23, 881–883.
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13. (a) Huisgen, R.; Blaschke, H.; Brunn, E. Tetrahedron Lett. 1966, 7, 405–409; (b)
Brunn, E.; Huisgen, R. Angew. Chem., Int. Ed. Engl. 1969, 8, 513–515.
14. (a) Hughs, D. L. Org. Prep. Proced. Int. 1996, 28, 127–164; (b) Prakash, G. K. S.;
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4.3.2.2. 4-Carbethoxyamino-2,5-diphenyl-2H-1,2,4-triazol-
3(4H)-one (6a). White solid; mp 144–145 ꢀC; 1H NMR (500 MHz,
DMSO):
d
8.63 (br, 1H), 8.02 (d, J¼8.0 Hz, 2H), 7.84 (d, J¼6.9 Hz, 2H),
7.46 (m, 5H), 7.23 (m, 1H), 4.18 (q, J¼6.9 Hz, 2H), 1.20 (m, 3H); 13C
NMR (125 MHz, DMSO):
d 155.7, 151.3, 146.1, 137.8, 131.2, 129.2,
129.0, 127.9, 126.1, 125.4, 119.1, 63.4, 14.4; HRMS (ESI) calcd for
C17H16N4O3 ([MþNa]þ): 347.1115, found: 347.1106; IR (KBr)
n
(cmꢁ1): 3211, 1753, 1712, 1495, 1458, 1241.
4.3.2.3. 4-Carbethoxyamino-5-nonyl-2-phenyl-2H-1,2,4-triazol-
3(4H)-one (6b). White solid; mp 65–66 ꢀC; 1H NMR (500 MHz,
CDCl3):
d
8.70 (br, 1H), 7.93 (d, J¼8.2 Hz, 2H), 7.40 (m, 2H), 7.21 (m,
1H), 4.19 (q, J¼6.8 Hz, 2H), 2.55 (t, J¼7.8 Hz, 2H), 1.72 (m, 2H), 1.40
(m, 2H), 1.31 (m, 13H), 0.88 (m, 3H); 13C NMR (125 MHz, CDCl3):
d
155.6, 151.0, 148.7, 137.8, 129.1, 125.8, 118.9, 63.2, 32.1, 29.6, 29.5,
15. (a) Nair, V.; Biju, A. T.; Abhilash, K. G.; Menon, R. S.; Suresh, E. Org. Lett. 2005, 7,
2121–2123; (b) Nair, V.; Biju, A. T.; Vinod, A. U.; Suresh, E. Org. Lett. 2005, 7,
5139–5142; (c) Nair, V.; Biju, A. T.; Mohanan, K.; Suresh, E. Org. Lett. 2006, 8,
2213–2216; (d) Nair, V.; Mathew, S. C.; Biju, A. T.; Suresh, E. Angew. Chem., Int.
Ed. 2007, 46, 2070–2073.
29.4, 29.3, 25.7, 25.0, 22.9, 14.4, 14.3; HRMS (ESI) calcd for
C20H30N4O3 ([MþNa]þ): 397.2210, found: 397.2213; IR (KBr)
n
(cmꢁ1): 3175, 2926, 1754, 1705, 1549, 1502, 1256.
16. Cui, S. L.; Wang, J.; Wang, Y. G. Org. Lett. 2008, 10, 13–16.
17. CCDC 761051, CCDC 761049, and CCDC 761050 contain the supplementary crys-
tallographic data for compounds 3i, 3l, and 5a, respectively. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336033.
18. (a) Gillis, B. T.; Beck, P. E. J. Org. Chem. 1962, 27, 1947–1951; (b) Franzus, B.;
Surridge, J. H. J. Org. Chem. 1962, 27, 1951–1957.
4.3.2.4. 4-Carbethoxyamino-2-phenyl-5-tert-butyl-2H-1,2,4-tri-
azol-3(4H)-one (6c). White solid; mp 113–114 ꢀC; 1H NMR
(500 MHz, CDCl3): d 8.60 (br, 1H), 7.95 (m, 2H), 7.41 (m, 2H), 7.19 (m,
1H), 4.21 (q, J¼7.0 Hz, 2H), 2.94 (m, 1H), 1.32 (d, J¼7.0 Hz, 6H), 1.22
(t, J¼7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3):
d 155.8, 152.5, 151.2,
137.9, 129.1, 125.8, 118.9, 63.3, 25.6, 19.7, 14.4; HRMS (ESI) calcd for
19. Durden, J. A., Jr.; Heywood, D. L. J. Org. Chem. 1965, 30, 4359–4361.