Isoquinoline-catalyzed addition of 2-bromo-1-aryl-1-ethanone to dialkyl azodicarboxylate: Synthesis of trialkyl 2-[(1E)-N-(alkoxycarbonyl)-2-aryl-2- oxoethanehydrazonoyl]hydrazine-1,1, 2-tricarboxylate

Article abstract of DOI:10.1007/s00706-011-0643-y

A catalytic method for the synthesis of a class of hydrazine derivatives is reported. The described method provides convenient access to compounds which are anticipated to show biological activities. The salient features of this process include operational simplicity, good yields, and easily accessible starting materials.

Full text of DOI:10.1007/s00706-011-0643-y

Monatsh Chem (2012) 143:255–262
DOI 10.1007/s00706-011-0643-y
ORIGINAL PAPER
Isoquinoline-catalyzed addition of 2-bromo-1-aryl-1-ethanone
to dialkyl azodicarboxylate: synthesis of trialkyl 2-[(1E)-N-
(alkoxycarbonyl)-2-aryl-2-oxoethanehydrazonoyl]hydrazine-1,1,
2-tricarboxylate
•
Ebrahim Kianmehr Alireza Bakhtiary
•
Chengjian Zhu
Received: 9 August 2010 / Accepted: 28 August 2011 / Published online: 7 October 2011
Ó Springer-Verlag 2011
Abstract A catalytic method for the synthesis of a class
of hydrazine derivatives is reported. The described method
provides convenient access to compounds which are
anticipated to show biological activities. The salient fea-
tures of this process include operational simplicity, good
yields, and easily accessible starting materials.
isoniazide (1) is the mainstay of antituberculosis therapy.
The tubercle bacilli lose their acid-fastness and viability
when exposed to isoniazide [8–10]. Compound 2, known as
Rh-5849, has been found to have commercial-level activity
against a range of insect pest species, whereas—most
importantly—it was judged to have a benign ecotoxicolog-
ical profile and be nontoxic to beneficial insect species.
Compound 3, which is a chlorinated derivative of 2, has been
found to mimic the action of 20-hydroxyecdysone in insects.
Two other analogs, tebufenozide (4) and halofenozide (5),
known as Rh-5992 and Rh-6345, respectively, show similar
activities and exhibit high specific toxicity to non-lepi-
dopteran species [1–3, 7]. Iproniazid (6) and phenelzine (7)
are used as antidepressants with monoamine-oxidase inhibi-
tory effects, and hydralazine (8) is used as an antihypertensive
drug [11] (Fig. 1). As a result of considerable interest in
substituted hydrazines, the synthesis of hydrazine derivatives
is a matter of significant interest from both theoretical and
practical perspectives [12–15].
Keywords Ylides Á Diazo compounds Á Amines Á
Catalysis
Introduction
Hydrazine derivatives are currently of considerable technical
and commercial importance; they are used in the pharma-
ceutical, agrochemical, polymer, and dye industries, and as
precursors in organic synthesis [1–3]. Hydrazines have found
applications in a large number of areas. Many of them show
remarkable biological activities and various similar com-
pounds have been shown to be effective for the treatment of
hypertension, tuberculosis, and Parkinson’s disease [1–3].
Some hydrazines display neuroprotective properties and are
used as antidepressant drugs [4]. Hydrazine-based pepti-
domimetics (aza-peptides) were found to be potent agents
against hepatitis [5], AIDS [6], and SARS [7]. For example,
Monosubstituted hydrazines can be prepared by hydra-
zine alkylation, by reducing C=N bonds of hydrazones, or
by direct amination and amination via diaziridines [16, 17].
1,1- and 1,2-disubstituted hydrazines can be prepared by
alkylation of free or suitably substituted hydrazines or via
the reduction of N-nitroso secondary amines or hydrazones
and hydrazides. Tri- and tetrasubstituted hydrazines are
also prepared by similar alkylation and reduction pro-
cesses. However, the alkylation of hydrazines is difficult to
control and generally produces mixtures containing higher
alkylated products [16, 17].
E. Kianmehr (&) Á A. Bakhtiary
School of Chemistry, College of Science, University of Tehran,
1417614411 Tehran, Iran
e-mail: kianmehr@khayam.ut.ac.ir
Conjugate addition to azodicarboxylates is one of the
preferred methods of electrophilic amination, and has been
used in the preparation of hydrazines [18–20]. Several
groups have presented the direct amination of active
methine compounds such as aldehydes [21–23], ketones
C. Zhu
School of Chemistry and Chemical Engineering,
State Key Laboratory of Coordination Chemistry,
Nanjing University, 210093 Nanjing,
People’s Republic of China
123

256
E. Kianmehr et al.
Fig. 1 Structures of some
biologically active hydrazine
derivatives
H2N
NH
O
NHNH2
O
NHNH
H2N
NH
O
N
Ar2
N
N
Ar1
N
H
O
N
N
2 Ar1, Ar2 = Phenyl
7
8
1
6
3 Ar1, Ar2 = 4-Chlorophenyl
4 Ar1= 4-Ethylphenyl, Ar2 = 3,5-Dimethylphenyl
5 Ar1 = 4-Chlorophenyl, Ar2 = Phenyl
Ar CO 2R
CO 2R
Ar CO 2R
O
N
N
N
N
CO 2R
O
H
N
Ar
RO C
O
O
H
N
C
N
NH CO 2R
N
CO2R
N
CO 2R
Ar
2
N
N
base
+
CO 2R
CO 2R
Ar CO R
2CO2R
RO C
2
N
N
N
O
H
N
+
A
B
N
N
CO2R
CO R
2
N
A
CO2R
Scheme 1
Scheme 2
[24], b-ketoesters [25–34], b-ketophosphonates [35, 36], a-
cyanoacetates [37], and a-cyanoketones [38–40] in the
presence of metal complexes or organocatalysts. Other
methods of amination using sources of electrophilic nitro-
gen including sulfonyl azides [41], sulfonyloxycarbamates
[42], 1-chloro-1-nitroso reagents [43], and oxaziridines
[44] have also been developed.
on the reaction. Table 1 shows that the reaction using
CH2Cl2 as the solvent and K2CO3 as the base gave the best
results at room temperature.
Based on the above results and the previous report by
Jones et al. [52], we turned our attention to investigating
the isoquinoline-catalyzed addition of phenacyl bromides
to dialkyl azodicarboxylate (Table 2). At first we examined
the reaction of phenacyl bromide with diisopropyl diazo-
dicarboxylate in the presence of a catalytic amount of
isoquinoline (15 mol%), K2CO3 as the base, and CH2Cl2 as
the solvent at room temperature (Table 2, entry 1). Despite
the increased reaction time (24 h), the reaction led to the
desired product in good yield. To reduce the reaction time, the
reaction was carried out in CH3CN under reflux conditions,
and it had completed after 3 h. The reaction was also moni-
tored with different catalyst loadings. At lower catalyst
loadings(10and5 mol%),thereactiontooklonger anddidnot
complete, even after stirring for 48 h. Also, to consider the
influence of the ylide type (an intermediate formed during the
reaction), the reactions of other nitrogen, phosphorus, and
arsine ylides were investigated under the abovementioned
reaction conditions. The results are summarized in Table 2.
As the results in Table 2 show, the catalyst is of crucial
importance, and the best result for the formation of 1 was
obtained in the presence of isoquinoline. Pyridine, tri-
phenylphosphine, and DABCO mainly led to the formation
of a 1:1 adduct of phenacyl bromide and dialkyl azodi-
carboxylate. When the optimized conditions were used, the
reactions of various phenacyl bromides with alkyl azodi-
carboxylates afforded good yields of trialkyl 2-[(1E)-N-
(alkoxycarbonyl)-2-aryl-2-oxoethanehydrazonoyl]hydra-
zine-1,1,2-tricarboxylates (Table 3). Finally, to further
Results and discussion
In this work we would like to report an efficient procedure
for the synthesis of a class of hydrazines with structure A,
which contains both hydrazone and hydrazine functional-
ities. Compound A can be readily reduced to hydrazine
B (Scheme 1).
As hydrazine derivatives with similar structures have
been shown to have biological activities, it is expected that
the abovementioned derivatives of hydrazine will also
show interesting pharmacological effects.
Ylide research has evolved in recent years, and ylides
are now powerful and versatile synthetic tools in organic
chemistry [45–48]. As a part of our current studies on the
development of efficient methods for the preparation of
heterocyclic compounds using ylide chemistry [49–51], we
investigated the reaction of nitrogen ylides (prepared by the
reaction of phenacyl bromide derivatives and isoquinoline)
with dialkyl azodicarboxylates, in order to consider the
possibility of forming C via a cyclization reaction. As
Scheme 2 shows, the reaction led to the formation of
A along with the liberation of isoquinoline.
To explore the scope and versatility of this procedure,
we first investigated the effects of solvent and temperature
123

Isoquinoline-catalyzed addition of 2-bromo-1-aryl-1-ethanone to dialkyl azodicarboxylate
257
Table 1 The effects of the base and solvent on the reaction of the isoquinolinium salt of phenacyl bromide with diisopropyl azodicarboxylate
O
O
N
O
Ph
O
O
Base, solvent
rt
O
N
O
O
N
N
1
O
H
O
N
+
2
O
Ph
N
O
N
O
Br
O
Entry
Base
Solvent
Time/h
Yield/%
1
2
3
4
5
6
7
KOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
THF
8
8
83
85
\5
63
78
74
71
K2CO3
Et3N
10
10
8
DBU
K2CO3
K2CO3
K2CO3
8
DMF
8
Table 2 The effects of the catalyst and the temperature on the reaction of phenacyl bromide with diisopropyl azodicarboxylate
O
O
N
O
Ph
O
O
O
N
O
O
N
N
Catalyst
O
H
O
2
+
1
Br
O
Ph
Base, solvent
N
O
N
O
O
Entry
Catalyst
Temperature
Solvent
Time/h
Yield of 1/%
1
2
3
4
5
6
7
Isoquinoline
Isoquinoline
Pyridine
rt
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
24
3
82
87
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
6
\5
64
N-Methylimidazole
DABCO
3
6
\5
\5
\5
Triphenylphosphine
Triphenylarsine
6
6
explore the potential of this protocol for the synthesis of
this class of hydrazine derivatives, we investigated a
reaction involving chloroacetonitrile and obtained triiso-
propyl 2-[(1E)-2-cyano-N-(isopropoxycarbonyl)-2-oxoeth-
anehydrazonoyl]hydrazine-1,1,2-tricarboxylate in moderate
yield (Table 3, entry 14).
The 1H NMR spectrum of 1 exhibited four doublet
signals that were readily recognized as arising from iso-
propyl methyl groups at d = 1.15, 1.23, 1.37, and
1.38 ppm and isopropyl methine groups at d = 4.83, 4.95,
and 5.16 ppm. Aromatic protons gave rise to character-
istic signals in the aromatic region of the spectrum. The
NH proton appeared at 8.51 ppm as a broad signal. The
proton-decoupled 13C NMR spectrum of 1 showed 16
distinct resonances, in agreement with the proposed
The structures of the products were characterized by
spectroscopic analysis and further confirmed by the X-ray
diffraction of 1 as a representative example (Fig. 2).
123

258
E. Kianmehr et al.
Experimental
Table 3 Reactions of 2-bromoacetophenones with dialkyl azodi-
carboxylates under the optimized reaction conditions
R
All chemicals and solvents were purchased from Merck and
used without further purification. Thin layer chromatography
(TLC) analysis was performed using Silicycle precoated TLC
plates (silica gel 60 F254). The products were purified by
preparative column chromatography on silica gel (0.063–
0.200 mm; Merck). Melting points were measured on an
Electrothermal9200apparatus.IRspectraweremeasuredona
Shimadzu FT-IR-4300 spectrometer. 1H and 13C NMR
spectra (in CDCl3) were measured with a Bruker Avance
DRX-500 Advance (1H NMR 500.1 MHz and 13C NMR
125.7 MHz). Mass spectra were recorded on an HP 5973 GC–
MS instrument operating at an ionization potential of 70 eV.
O
O
R
O
O
Ar
N
O
R
N
O
O
O
N
N
O
H
N
+
2
Br
N
O
O
Ar
R
O
R
O
O
R
1-14
Entry
Ar
Ph
R
Product
Yield / %
1
Pri
Pri
Pri
Pri
Pri
Pri
Et
1
87
73
65
90
85
83
57
76
81
80
68
49
53
40
2
4-BrPh
2
General procedure for the synthesis of triisopropyl-
2-[(1E)-N-(isopropoxycarbonyl)-2-oxo-2-
phenylethanehydrazonoyl]hydrazine-1,1,2-
tricarboxylate (1, C24H34N4O9)
3
4-MeOPh
4-PhPh
3
4
4
5
4-NO2-Ph
4-ClPh
3-BrPh
Ph
5
6
6
Into a 25 cm3 round bottom flask, phenacyl bromide
(1 mmol) and diisopropyl azodicarboxylate (2 mmol) were
added in the presence of 15 mol% of isoquinoline in
10 cm3 acetonitrile. Then the reaction mixture was stirred
under reflux for 3 h. The progress of the reaction was
monitored by the fading of the yellow color and also by
TLC. After the reaction had completed, the solvent was
removed under reduced pressure, water was added, and the
reaction mixture was extracted with dichloromethane. The
organic layer was dried over anhydrous Na2SO4, and then
the solvent was removed. Diethyl ether was added to the
resulting oily crude product. It was cooled overnight and
the precipitated solid formed was recrystallized from eth-
anol to obtain the pure product as yellow crystals (87%);
7
7
8
Et
8
9
4-PhPh
4-ClPh
4-MeOPh
Ph
Et
9
10
11
12
13
14
Et
10
11
12
13
14
Et
But
But
Pri
4-ClPh
ClMe
structure. The carbonyl group of 1 appears at d =
185.5 ppm.
Although we have not established the mechanism of the
reaction in an experimental manner, a possible explanation
is shown in Scheme 3. The reaction of isoquinoline with
phenacyl bromide derivatives leads to quaternary ammo-
nium salt D. Deprotonation of D with K2CO3 forms the
corresponding ylide, which would attack dialkyl azodi-
carboxylate in a Michael addition manner to yield the
intermediate E. The intermediate E undergoes a 1,3-
hydrogen shift to produce ylide F. The intermediate F adds
to dialkyl azodicarboxylate to form G. The intramolecular
rearrangement of G, via intermediate H, leads to the
intermediate I, which can easily eliminate isoquinoline to
afford the hydrazine A.
ꢀ
m.p.: 122–124 °C; IR (KBr) m = 3,238, 2,937, 1,766,
1,730, 1,704, 1,681, 1,598, 1,481, 1,409, 1,367, 1,305,
1
1,232, 1,100, 1,020 cm-1; H NMR (500.1 MHz, CDCl3):
d = 1.15 (d, J = 6.2 Hz, 6H), 1.23 (d, J = 6.2 Hz, 6H),
1.37 (d, J = 6.2 Hz, 6H), 1.38 (d, J = 6.2 Hz, 6H), 4.83
(m, 1H), 4.95 (m, 1H), 5.16 (m, 2H), 7.51 (m, 2H), 7.62 (m,
1H), 8.19 (d, J = 7.5 Hz, 2H), 8.51 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 22.0, 22.1, 22.2, 22.3, 70.1,
72.9, 73.0, 74.1, 129.1, 129.3, 134.6, 135.8, 150.8, 151.3,
153.2, 185.5 ppm; MS (EI, 70 eV): m/z (%) = 522 (2), 417
(6), 350 (6), 308 (4), 290 (5), 266 (9), 222 (17), 204 (20),
191 (8), 178 (25), 161 (15), 132 (17), 105 (100).
In conclusion, we have developed a catalytic and efficient
methodology for the synthesis of trialkyl 2-[(1E)-N-(alkoxy-
carbonyl)-2-aryl-2-oxoethanehydrazonoyl]hydrazine-1,1,-
2-tricarboxylate. Simplicity of operation, easily accessible
starting materials, good yields, easy work-up, and the puri-
fication of compounds by a nonchromatographic method
(crystallization only) are the key advantages of this method.
Triisopropyl 2-[(1E)-2-(4-bromophenyl)-N-
(isopropoxycarbonyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (2, C24H33BrN4O9)
ꢀ
White solid (73%); m.p.: 142–143 °C; IR (KBr) m = 3,315,
2,985, 1,780, 1,728, 1,674, 1,587, 1,529, 1,377, 1,317,
1
1,290, 1,263, 1,226, 1,180, 1,099, 1,020 cm-1; H NMR
123

Isoquinoline-catalyzed addition of 2-bromo-1-aryl-1-ethanone to dialkyl azodicarboxylate
259
600 (M?, 79Br, 3), 500 (3), 457 (1), 443 (1), 430 (7), 417
(20), 344 (20), 300 (20), 284 (27), 256 (29), 212 (20), 185
(100), 155 (17), 106 (27).
Triisopropyl 2-[(1E)-N-(isopropoxycarbonyl)-2-
(4-methoxyphenyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (3, C25H36N4O10)
Greenish white solid (65%); m.p.: 124–126 °C; IR (KBr)
ꢀ
m = 3,421, 2,987, 1,770, 1,735, 1,664, 1,596, 1,514, 1,375,
1,263, 1,228, 1,180, 1,097, 1,024, 937 cm-1 1H NMR
;
(500.1 MHz, CDCl3): d = 1.19 (d, J = 6.2 Hz, 6H), 1.23
(d, J = 6.2 Hz, 6H), 1.38 (d, J = 6.2 Hz, 6H), 1.39 (d,
J = 6.2 Hz, 6H), 3.90 (s, 3H), 4.87 (m, 1H), 4.96 (m, 1H),
5.15 (m, 2H), 7.00 (d, J = 8.6 Hz, 2H), 8.21 (d,
J = 8.6 Hz, 2H), 8.35 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 22.0, 22.1, 22.2, 22.3, 56.0,
69.9, 72.8, 72.9, 73.9, 114.7, 128.6, 131.8, 132.5, 150.8,
151.3, 153.0, 165.0, 184.1 ppm; MS (EI, 70 eV): m/z
(%) = 552 (3), 417 (6), 380 (3), 320 (3), 294 (4), 252 (6),
234 (20), 208 (15), 162 (22), 135 (100).
Fig. 2 X-ray crystal structure of 1
Triisopropyl 2-[(1E)-2-(biphenyl-4-yl)-N-
(isopropoxycarbonyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (4, C30H38N4O9)
(500.1 MHz, CDCl3): d = 1.19 (d, J = 6.2 Hz, 6H), 1.26
(d, J = 6.2 Hz, 6H), 1.40 (t, J = 6.2 Hz, 12H), 4.85 (m,
1H), 5.00 (m, 1H), 5.17 (m, 2H), 7.67 (d, J = 8.3 Hz, 2H),
8.30 (d, J = 8.3 Hz, 2H), 8.69 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 22.0, 22.1, 22.2, 22.3, 70.2,
73.13, 74.2, 129.9, 130.6, 132.7, 134.8, 150.9, 153.3,
184.4 ppm; MS (EI, 70 eV): m/z (%) = 602 (M?, 81Br, 3),
ꢀ
Yellow solid (90%); m.p.: 137–138 °C; IR (KBr) m
= 3,421, 2,935, 1,770, 1,735, 1,672, 1,604, 1,523, 1,375,
1
1,261, 1,226, 1,180, 1,093 cm-1; H NMR (500.1 MHz,
CDCl3): d = 1.20 (d, J = 6.2 Hz, 6H), 1.27 (d,
J = 6.2 Hz, 6H), 1.42 (d, J = 6.2 Hz, 6H), 1.43 (d,
Scheme 3
Ar
CO2R
O
Q
O
N
H
Br
N
N
CO2R
Ar
N
RO2C
N
RO2C
A
O
D
Q
Ar
K2CO3
RO2C
Ar
N N
Q CO2R
O
H
CO2R
N
I
N
N
RO2C
Ar
Q
CO2R
N
O
N
RO2C
N
E
CO2R
RO2C
Ar
Q
CO2R
O
Ar
N
H
O
H
H
Q
N
N
CO2R
OR
N
Ar
N
RO2C
O
N
CO2R
CO2R
Q
CO2R
F
O
N
H
N
CO2R
N
N
CO2R
RO2C
RO2C
N N
CO2R
G
123

260
E. Kianmehr et al.
J = 6.2 Hz, 6H), 4.89 (m, 1H), 5.00 (m, 1H), 5.20 (m, 2H),
7.46 (m, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.67 (d,
J = 7.3 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 8.32 (d,
J = 8.0 Hz, 2H), 8.54 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 22.0, 22.1, 22.2, 22.3, 70.1,
72.9, 73.0, 74.1, 127.7, 128.0, 128.9, 129.4, 129.8, 134.5,
140.1, 147.3, 150.8, 151.4, 151.9, 153.2, 185.1 ppm; MS
(EI, 70 eV): m/z (%) = 598 (1), 417 (5), 366 (4), 340 (3),
322 (5), 298 (5), 280 (26), 254 (10), 208 (16), 181 (100),
152 (21).
64.8, 65.0, 123.5, 127.7, 130.9, 131.7, 137.4, 137.5, 151.2,
153.6, 184.0 ppm; MS (EI, 70 eV): m/z (%) = 546 (M?,
81Br, 2), 544 (M?, 79Br, 2), 430 (2), 384 (2), 361 (45), 325
(6), 297 (8), 284 (20), 269 (8), 212 (14), 185 (100), 157
(25), 129 (24).
Triethyl 2-[(1E)-N-(ethoxycarbonyl)-2-oxo-2-phenyl-
ethanehydrazonoyl]hydrazine-1,1,2-tricarboxylate (8)
White solid (76%); m.p.: 100–101 °C (89–90 °C [52]).
Triethyl 2-[(1E)-2-(biphenyl-4-yl)-N-(ethoxycarbonyl)-
2-oxoethanehydrazonoyl]hydrazine-1,1,2-tricarboxylate
(9, C26H30N4O9)
Triisopropyl 2-[(1E)-N-(isopropoxycarbonyl)-2-
(4-nitrophenyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (5, C24H33N5O11)
Yellow solid (81%); m.p.: 111–113 °C; IR (KBr)
ꢀ
m = 3,141, 2,910, 1,766, 1,750, 1,703, 1,677, 1,600,
1,488, 1,423, 1,373, 1,350, 1,247, 1,224, 1,093, 1,016,
Greenish white solid (85%); m.p.: 157–159 °C; IR (KBr)
ꢀ
m = 3,315, 2,986, 1,776, 1,721, 1,682, 1,526, 1,375, 1,344,
972 cm-1 1H NMR (500.1 MHz, CDCl3): d = 1.17 (t,
;
1,221, 1,094 cm-1 1H NMR (500.1 MHz, CDCl3):
;
J = 7.0 Hz, 3H), 1.23 (t, J = 7.0 Hz, 3H), 1.39 (t,
J = 7.0 Hz, 6H), 4.15 (m, 4H), 4.41 (q, J = 7.0 Hz, 4H),
7.40 (m, 1H), 7.47 (t, J = 7.3 Hz, 2H), 7.62 (d,
J = 7.3 Hz, 2H), 7.72 (d, J = 7.8 Hz, 2H), 8.26 (d,
J = 7.8 Hz, 2H), 8.54 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 14.4, 14.5, 14.7, 62.3, 64.4,
64.8, 127.4, 127.6, 128.8, 129.3, 129.7, 134.3, 140.0,
147.3, 151.2, 151.7, 153.4, 153.6, 185.0 ppm; MS (EI,
70 eV): m/z (%) = 542 (7), 496 (10), 424 (5), 398 (2), 361
(16), 308 (5), 292 (4), 280 (18), 265 (5), 241 (4), 208 (10),
181 (100), 153 (27).
d = 1.15 (d, J = 6.2 Hz, 6H), 1.27 (d, J = 6.2 Hz, 6H),
1.40 (t, J = 6.2 Hz, 12H), 4.79 (m, 1H), 5.00 (m, 1H), 5.17
(m, 2H), 8.35 (d, J = 8.7 Hz, 2H), 8.45 (d, J = 8.7 Hz,
2H), 9.14 (b, 1H) ppm; 13C NMR (125.7 MHz, CDCl3):
d = 21.9, 22.1, 22.14, 22.3, 70.4, 73.3, 73.3, 124.2, 129.9,
141.0, 150.8, 151.0, 153.7, 183.6 ppm; MS (EI, 70 eV):
m/z (%) = 567 (1), 417 (3), 395 (3), 353(6), 324 (4), 311
(20), 267 (10), 249 (12), 223 (15), 177 (19), 150 (19).
Triisopropyl 2-[(1E)-2-(4-chlorophenyl)-N-
(isopropoxycarbonyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (6, C24H33ClN4O9)
Triethyl 2-[(1E)-2-(4-chlorophenyl)-N-(ethoxycarbonyl)-
2-oxoethanehydrazonoyl]hydrazine-1,1,2-tricarboxylate
(10, C20H25ClN4O9)
ꢀ
White solid (83%); m.p.: 140–142 °C; IR (KBr) m = 3,314,
2,984, 1,775, 1,726, 1,675, 1,584, 1,524, 1,406, 1,374,
1
1,258, 1,221, 1,177, 1,094 cm-1; H NMR (500.1 MHz,
ꢀ
White solid (80%); m.p.: 137–139 °C; IR (KBr) m = 3,314,
2,987, 1,757, 1,756, 1,674, 1,583, 1,522, 1,376, 1,338,
CDCl3): d = 1.18 (d, J = 6.2 Hz, 6H), 1.26 (d,
J = 6.2 Hz, 6H), 1.40 (t, J = 6.2 Hz, 12H), 4.85 (m,
1H), 4.99 (m, 1H), 5.16 (m, 2H), 7.59 (d, J = 8.7 Hz, 2H),
8.20 (d, J = 8.7 Hz, 2H), 8.6 (b, 1H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 22.0, 22.1, 22.2, 22.3, 70.2,
73.0, 73.1, 74.2, 129.6, 130.5, 134.3, 141.0, 150.8, 153.3,
184.2 ppm; MS (EI, 70 eV): m/z (%) = 556 (1), 417 (14),
384 (9), 342 (8), 324 (7), 300 (22), 279 (11), 256 (25), 238
(22), 225 (9), 212 (30).
1,294, 1,208, 1,013, 751 cm-1 1H NMR (500.1 MHz,
;
CDCl3): d = 1.17 (t, J = 7.0 Hz, 3H), 1.25 (t, J = 7.0 Hz,
3H), 1.39 (t, J = 7.0 Hz, 6H), 4.13 (q, J = 7.0 Hz, 2H),
4.18 (q, J = 7.0 Hz, 2H), 4.40 (q, J = 7.0 Hz, 4H), 7.47
(d, J = 8.3 Hz, 2H), 8.16 (d, J = 8.3 Hz, 2H), 8.72 (b, 1H)
ppm; 13C NMR (125.7 MHz, CDCl3): d = 14.4, 14.5,
14.7, 62.4, 64.7, 64.9, 129.7, 130.5, 134.1, 141.0, 151.3,
151.7, 153.5, 184.2 ppm; MS (EI, 70 eV): m/z (%) = 500
(2), 379 (1), 361 (25), 310 (4), 281 (5), 266 (4), 253 (6),
238 (14), 225 (5), 166 (14), 139 (100), 111 (22).
Triethyl 2-[(1E)-2-(3-bromophenyl)-N-
(ethoxycarbonyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (7, C20H25BrN4O9)
Light yellow solid (57%); m.p.: 106–107 °C; IR (KBr)
Triethyl 2-[(1E)-N-(ethoxycarbonyl)-2-(4-methoxyphenyl)-
2-oxoethanehydrazonoyl]hydrazine-1,1,2-tricarboxylate
(11, C21H28N4O10)
ꢀ
m = 3,622, 3,281, 1,802, 1,726, 1,676, 1,513, 1,374, 1,225,
1
1,175, 1,083, 1,026 cm-1; H NMR (500.1 MHz, CDCl3):
Yellow solid (68%); m.p.: 114–115 °C; IR (KBr)
d = 1.18 (t, J = 7.2 Hz, 3H), 1.25 (t, J = 7.2 Hz, 3H),
1.38 (t, J = 7.2 Hz, 6H), 4.14 (q, J = 7.2 Hz, 2H), 4.18 (q,
J = 7.2 Hz, 2H), 4.22 (q, J = 7.2 Hz, 4H), 7.39 (t,
J = 7.8 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 8.15 (d,
J = 7.8 Hz, 1H), 8.30 (s, 1H), 8.73 (b, 1H) ppm; 13C
NMR (125.7 MHz, CDCl3): d = 14.5, 14.6, 14.8, 62.5,
ꢀ
m = 3,280, 2,981, 1,726, 1,658, 1,595, 1,507, 1,375,
1,259, 1,221, 1,164, 1,088, 1,019, 847 cm-1 1H NMR
;
(500.1 MHz, CDCl3): d = 0.84 (t, J = 7.0 Hz, 3H), 1.20 (t,
J = 7.0 Hz, 3H), 1.29 (t, J = 7.0 Hz, 3H), 1.34 (t,
J = 7.0 Hz, 3H), 4.13 (m, 4H), 4.36 (q, J = 7.0 Hz, 2H),
123

Isoquinoline-catalyzed addition of 2-bromo-1-aryl-1-ethanone to dialkyl azodicarboxylate
261
6.94 (d, J = 8.0 Hz, 2H), 8.22 (d, J = 8.0 Hz, 2H) ppm;
13C NMR (125.7 MHz, CDCl3): d = 14.3, 14.5, 14.7, 55.9,
62.2, 64.5, 64.8, 65.5, 114.7, 129.0, 131.8, 151.2, 152.5,
153.2, 153.8, 165.1, 183.9 ppm; MS (EI, 70 eV): m/z
(%) = 496 (1), 406 (4), 378 (4), 334 (19), 306 (9), 275 (4),
262 (31), 247 (13), 234 (21), 219 (9), 191 (3), 174 (4), 162
(6), 135 (100).
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White solid (49%); m.p.: 172–174 °C; IR (KBr) m = 3,255,
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Tri-tert-butyl 2-[(1E)-N-(tert-butoxycarbonyl)-2-
(4-chlorophenyl)-2-oxoethanehydrazonoyl]-
hydrazine-1,1,2-tricarboxylate (13, C28H41ClN4O9)
ꢀ
White solid (53%); m.p.: 154–155 °C; IR (KBr) m = 3,312,
2,985, 1,770, 1,756, 1,674, 1,583, 1,523, 1,376, 1,329,
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;
CDCl3): d = 1.35 (s, 9H), 1.53 (s, 18H), 1.56 (s, 9H), 7.53
(d, J = 8.2 Hz, 2H), 8.46 (d, J = 8.2 Hz, 2H), 8.70 (b, 1H)
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Triisopropyl 2-[(1E)-2-cyano-N-(isopropoxycarbonyl)-2-
oxoethanehydrazonoyl]hydrazine-1,1,2-tricarboxylate
(14, C18H29N5O8)
ꢀ
Yellow oil (40%); IR (KBr) m = 2,984, 2,357, 1,743,
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1,514, 1,463, 1,372, 1,216, 1,085 cm-1 1H NMR
;
(500.1 MHz, CDCl3): d = 1.49 (d, J = 6.2 Hz, 6H), 1.54
(d, J = 6.2 Hz, 6H), 1.55 (d, J = 6.2 Hz, 6H), 1.58 (d,
J = 6.2 Hz, 6H), 5.28 (m, 4H) ppm; 13C NMR
(125.7 MHz, CDCl3): d = 21.8, 21.9, 22.0, 22.1, 22.2,
71.8, 74.0, 74.9, 75.2, 113.0, 151.1, 151.5, 151.7,
151.9 ppm; MS (EI, 70 eV): m/z (%) = 443 (9), 400 (9),
358 (16), 316 (9), 298 (3), 272 (12), 256 (3), 229 (33), 187
(100), 170 (9), 143 (33).
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Acknowledgments Financial support by the research council of the
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Gajewski, Canadian Intellectual Property Office, for helpful com-
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