Synthesis of benzyl hydrazine derivatives: Via amination of benzylic C(sp3)-H bonds with dialkyl azodicarboxylates

Article abstract of DOI:10.1039/c7nj04880g

A novel synthesis of benzyl hydrazines through oxidative amination of benzylic C-H bonds has been developed. The resulting aminated products are accessed directly from the reaction of alkylarenes with dialkyl/diphenyl azodicarboxylates using Cu₂O/Phen as the catalytic system. The reaction proceeded smoothly and a decent range of N-substituted hydrazides was synthesized in acceptable to good yields. Both primary and secondary sp³ C-H sources afford only monoamination products.

Full text of DOI:10.1039/c7nj04880g

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Received 00th January 20xx,
Synthesis of Benzyl Hydrazine Derivatives via Amination of
Benzylic C (sp3)–H Bonds with Dialkyl Azodicarboxylates
A. Samzadeh-Kermani
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A novel synthesis of benzyl hydrazines through oxidative amination of benzylic C−H bonds has been developed. The
resulting aminated products are accessed directly from the reaction of alkylarenes with dialkyl/diphenyl azodicarboxylates
using Cu2O/Phen as catalytic system. The protocol proceeded smoothly and a decent range of N-sustituted hydrazides
were synthesized in acceptable to good yields. Both primary and secondary sp3 C–H sources afford only monoamination
products.
developed an outstanding stereoselective amination of benzylic C-H
with sulfonimidamides catalytic in chiral rhodium (II) complex.15
Intramolecular allylic and benzylic C-H amination has also been
developed.16-18 Pandey reported a benzylic C(sp3)–H amination
via visible-light-photoredox catalysis.19 DeBoef and co-workers have
Introduction
C−H functionalization is noted as an efficient and highly atome
conomic method for the formation of various chemical
compounds.1-3 In recent years, transition-metal and organo-catalyst
catalyzed C–H amination has made considerable achievements.
Particularly, selective amination of sp3 C−H bonds of alkyl benzenes
has attracted much attention due to the high prevalence of C−N
bonds in pharmaceuticals, agrochemicals, polymers, etc.4
disclosed an interesting chemo-selective amination of aromatic C-H
bond over benzylic C-H ones.20 Catalytic sp3 C−H amination are also
very well recapitulated in recent reviews.21-22
The alkyl hydrazine scaffold is a common motif in medicinal
chemistry and pharmaceuticals.23-24 Despite alkyl hydrazines
structural simplicity they are generally difficult to access. Direct
synthesis from unprotected hydrazine is known to be difficult and
low yielding, generally giving rise to complex mixtures of
products.25-26 Dialkyl azodicarboxylates (DAAD) have been broadly
employed as the amination partner for the synthesis of N-aryl
hydrazides.27-30 Inspired by previous reports, we herein report a
general and direct method for the synthesis of benzyl/phenyl
hydrazine derivatives through benzylic C-H amination with
azodicarboxylates using Cu2O/Phen as catalytic system.
Benzylic amines are important substructures in biologically active
compounds5 and the synthesis of such structures is typically
achieved through functional group interconversion processes. As
such, catalytic methods for selective amination of benzylic C−H
bonds would provide a strategic means to utilize this resource. In
this context, transition-metal-catalyzed nitrene insertions into C-H
bonds serve as direct and impactful procedure for the synthesis of
benzylic amine skeletons.6-8 Powell reported on the copper-
catalyzed amination of benzylic C-H Bonds with sulfonamides
resulting in the N-benzylated sulfonamide products.9 Emmert has
also utilized N-acetoxybenzenesulfonamides as amination reagents
for direct amination of benzylic C-H bond.10 Copper-catalyzed
amidation of benzylic hydrocarbons provides an efficient route to
produce N-benzyl amide derivatives.11 Amination of benzylic C-H
bond with imidazole has been reported via iron-catalyzed oxidative
activation of benzylic C-H Bonds.12 Zhu and co-workers have
developed an organo-catalytic route for amination of benzylic C–H
Results and Discussion
To begin our study, we chose toluene (1a) and diisopropyl
azodicarboxylate (2a) as model substrates (Table 1). We initially
examined di-tert-butyl peroxide (DTBP) as an oxidant without any
catalyst. While in the absence of a catalyst none of the targeted
diisopropyl 1-benzylhydrazine-1,2-dicarboxylate (3a) was detected
(entry 1), the use of FeCl2 led to a promising 23% yield (entry 2).
When the reaction was performed with FeCl2.4H2O instead of FeCl2,
the yield dropped to 11% (entry 3). Subsequent screening of
catalyst source revealed that Cu2O represented the optimum source
of catalyst for the reaction (entries 4−11). Although, CuCl and
[MeCN]4Cu(I)PF6 showed also a decent catalytic efficiency (entries
12 and 13). Commencing from previous works, the effect of ligand
on reaction outcome was also examined (entries 14-18). Among the
ligands examined, only 1,10-Phenantroline (phen) improved the
yield of the desired product (entry 14). While the exact function of
bonds.13 Bolm developed
a versatile route to N-benzylated
sulfoximines through the iron-catalyzed cross-dehydrogenative
coupling of sulfoximines with diarylmethanes.14 Muller has
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a
ligand is unclear, we found that the presence of ligand suppresses
Reaction conditions: 1a (2.0 mL), 2a (1.0 mmol), catalyst (0.15
the formation of compound 4 (see scheme 1a). Moreover, phen is mmol), ligand (0.10 mmol), oxidant (2.0 mmol), 4 Å MS (300 mg),
known ligand for copper-catalyzed C-N bond formation27 and it 110 °C for 28 h, in a sealed tube under an argon atmosphere. b 1.5
c
d
capable of bidentate coordination to copper salts, as such a working mmol of DTBP was used. 1 mL of H2O was used. 0.10 mmol of
hypothesis is that it increases the solubility of copper salts in such Cu2O and 0.06 mmol of Phen were used. e 1.0 mL of 1a was used.
non-polar media. Attempts to use alternative oxidants such as tert- Phen
=
1,10-Phenantroline, Bipyr
=
bipyridine, L1
=
1,3-
4-
butyl hydroperoxide (TBHP), dioxygen, PhI(OAc)2, and (NH4)2S2O8 diphenylpropanedione, L2
were unsatisfactory (Table 1, entries 19−22). However, reaction dimethylamino pyridine.
conducted with benzoyl peroxide (BPO) as the oxidant source
=
1,3-indanedione, DMAP
=
formed the desired product in moderated yield (entry 23). Note Under the optimized conditions, the oxidative amination of a
that the reaction conducted with 1.5 equiv of DTBP, formed the variety of benzylic hydrocarbons was investigated (Table 2). p-, m-,
desired product in 84% yield (entry 24). The study also indicates And o-xylenes were tolerated (1b−1d). p- And m- xylenes afforded
that the presence of H2O inhibits the reaction (entry 25) which also the corresponding aminated products in good yields however, o-
is in favor of proposed reaction pathway (Scheme 2). The yield xylene gave a lower yield probably due to the steric hindrance of
remained almost unchanged by reducing the amount of catalyst to the product (entries 2-4). The amination reactions of xylene
0.10 mmol (entry 26) however, the reaction proceeded poorly as derivatives with 2a only yielded monoaminated products. Further
the amount of catalyst reduced further (not shown in Table 1). study on the reaction of xylene derivatives indicated that the
Unfortunately, reducing the amount of the toluene resulted in presence of ligand inhibited the formation of the double amination
diminished yields (entry 27).
byproduct and simultaneously increasing the product yield (please
see SI section). To our delight, mesitylene could couple with 2a to
give an excellent yield of the desired product 3e (entry 5). Halogen-
containing alkyl benzenes were also examined. The results showed
that halogens could be well tolerated in this amination reaction
Table 1. Optimization of the reaction conditionsa
H
H
CO2i-Pr
CO2i-Pr
N
Catalyst, Oxidant
H
N
+
N
N
i-PrO2C
Ligand
(3f−3h), providing
a great opportunity for subsequent cross-
i-PrO2C
H
1a
2a
3a
coupling reactions (entries 6-8). Toluene with methylthio motif
afforded the product 3i in moderate yield (entry 9). Toluene
containing phenyl or methoxycarbonyl moieties 3j and 3k could
react, and the corresponding products were obtained in moderate
yields (entries 10-11). It could be deduced that the reaction does
not proceed via methylenyl cation intermediate. 1-Methoxy-4-
methylbenzene (1l) also afforded a good yield (entry 12). Direct N-
alkylation of 2a with secondary benzylic hydrocarbons like
ethylbenzene (1m) and propylbenzene (1n) were also successful,
but the yields were comparatively lower (entries 13 and 14). The
yield of a tertiary benzylic hydrocarbon was at a trace level
(detected by GC analysis, not shown in Table 2). Ungratefully,
cyclohexane did not work as a reaction partner with 2a and no
product arising from the amination of sp3 C−H bond of cyclohexane
is detected by GC analysis of the crude reaction mixture (not shown
in Table 2). We were pleased to note that diphenylmethane (1o)
oxidatively aminated to afford product 3o in moderate yield (entry
15). The selectivity of primary and secondary benzylic substrate was
also examined using 4-ethyltoluene (1p) (entry 16).31 Other dialkyl
azodicarboxylates 2b-2d were also examined as the amination
source and the corresponding N-benzylated products were
achieved in good yields (entries 17-22). Diphenyl azodicarboxylates
(2e) was also tolerated (entry 23). The reaction conducted with
dibenzyl azodicarboxylate (2f) formed a complex reaction mixture
(entry 24). Additionally, our optimized reaction conditions were not
suitable for amination of sp3 C−H of heteroaromatic substrates and
the presence of –OH, CH3COO-, CH3CO-, HCO-, -NH2, -NO2, or -CN
moiety on aromatic ring was not compatible with this amination
reaction.
Entry Catalyst
Oxidant
Ligand Yield (%)
1
2
3
-
DTBP
DTBP
DTBP
-
-
-
-
FeCl2
23
FeCl2.4H2O
traces
4
5
6
7
FeCl3
Fe(acac)3
CuBr
DTBP
DTBP
DTBP
DTBP
-
-
-
-
19
traces
37
CuI
31
8
9
Cu(OAc)2
CuO
DTBP
DTBP
DTBP
DTBP
DTBP
-
-
37
23
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
Cu2O
Cu
-
63
22
46
53
89
59
46
39
-
CuCl
-
[MeCN]4CuPF6 DTBP
-
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
DTBP
DTBP
DTBP
DTBP
DTBP
TBHP
O2
Phen
Bipyr
L1
L2
DMAP 50
Phen
Phen
Phen
26
-
PhI(OAc)2
traces
traces
59
(NH4)2S2O8 Phen
BPO
Phen
Phen
Phen
Phen
Phen
DTBP
DTBP
DTBP
DTBP
84b
tracesb,c
81b,d
61e
2 | New Journal of Chemistry., 2012, 00, 1-3
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Table 2. Amination of sp3 C-H with 2
R2
R2
CO2R3
CO2R3
H
Cu2O, DTBP
Phen, 110 °C
28 h
N
N
N
N
R1
R3O2C
+
R3O2C
H
R1
1
2
3
Entry
1
1
a
b
c
d
e
f
R1
H
R2
2
a
a
a
a
a
a
a
a
a
a
a
a
R3
Yield (%)
3a, 81
3b, 85
3c, 83
3d, 53
3e, 89
3f, 75
3g, 70
3h, 74
3i, 48
H
H
H
H
H
H
H
H
H
H
H
H
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
2
4-Me
3-Me
2-Me
3
4
5
3,5-dimethyl
4-Br
6
7
g
h
i
3-Cl
Scheme 1. Investigation into the reaction pathway
8
4-I
9
4-MeS
2-Ph
Based on our experimental results and previous reports,32-34
possible mechanism is depicted in Scheme 2. Firstly, DTBP
decomposes to the tert-butoxyl radical and species 5 in the
presence of Cu2O. Next, hydrogen is abstracted from the C-H bond
of methyl in toluene, giving the benzyl radical 6.33 Then addition of
radical species of 6 to the nitrogen–nitrogen double bond of
azodicarboxylate generates the radical intermediate 7.30 Finally,
the intermediate 7 is converted to the desired product 3 by the
action of t-BuOH or toluene. The latter is supported by the fact
that the reaction conducted with 1.5 equiv of DTBP also formed
the desired product in good yield (Table 1, entry 24).
Unfortunately, the exact role of copper salts and how do it
catalyze this transformation is still unclear, but it should be noted
that the reaction did not work well in absence of a catalyst source.
10
11
12
j
3j, 65
k
l
4-MeOCO
4-MeO
3k, 52
3l, 92
13
14
15
16
m
n
H
Me
Et
a
a
a
a
i-Pr
i-Pr
i-Pr
i-Pr
3m, 64
3n, 62
3o, 55
3p, 51
3p′, 27
3q, 82
3r, 83
H
o
H
Ph
H
p
4-Et
17
18
19
a
b
e
H
H
H
H
b
b
b
Et
Et
Et
4-Me
3,5-dimethyl
3s, 91
20
21
22
23
24
l
4-MeO
H
H
H
H
H
b
c
Et
3t, 89
a
a
a
a
H
H
H
H
Cy
3u, 84
d
e
f
t-Bu
Ph
Bn
3v, 76
3w, 90
complicated
a Reaction conditions: 1 (2.0 mL), 2 (1.0 mmol), Cu2O (0.10 mmol),
Phen (0.06 mmol), DTBP (1.5 mmol), 4 Å MS (300 mg), 110 °C for 28
h, in a sealed tube under an argon atmosphere.
To investigate the details of the mechanism for this reaction, we
performed some additional experiments. Adding the radical
scavenger such as 2,2,6,6-tetramethylpiperidinoxyl (TEMPO) into
the reaction mixture completely suppressed the formation of the
desired product which implied a radical process was involved in this
benzylic C-H amination (Scheme 1a). In the absence of toluene, a
traces amount of 4 was obtained which can indicate that hydrazide
radical is formed during the reaction progress (Scheme 1b). In
addition, an intermolecular competing kinetic isotope effect (KIE)
experiment was performed and it was observed with the kH/kD = 4.6
(Scheme 1c). This experiment indicates that the hydrogen
abstraction of the sp3 C–H bond should be involved in reaction
pathway.
Scheme 2. Plausible mechanism for the formation of N-benzyl
hydrazide derivatives
Experimental
All reagents, catalysts, and solvents were obtained from
commercial sources (Aldrich, Acros, Merck, Fluka). Solvents were
dried over molecular sieves 3Å or 4Å before the use. Molecular
sieves were activated in vacuum oven at 180 ˚C for 12 h and stored
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under vacuum at 100 °C in the presence of P4O10. The copper
catalysts were typically weighted into smaller vials containing about
500 mg of reagent in a glovebox and sealed. The smaller containers
were transferred outside the glovebox, stored in a desiccator while
being utilized and kept for no more than 2 weeks outside the
glovebox. tert-Butyl hydroperoxide (TBHP), di-tert-butyl peroxide
(DTBP), and benzoyl peroxide (BPO) were stored refrigerated. All
reactions were carried out in Schlenk tube (25 mL) using oven-dried
Notes and references
Diisopropyl 1-benzylhydrazine-1,2-dicarboxylate (3a)
Colorless solid, mp: 95-96.5 ˚C; yield: 0.24 g (81%). IR (KBr) (νmax
,
cm-1): 3292, 3035, 2927, 1618, 1555, 1322, 1140. 1H NMR (500.1
MHz, CDCl3): δH = 1.20 (6 H, d, 3J = 5.8 Hz, 2 Me), 1.26 (6 H, d, 3J =
6.1 Hz, 2 Me), 4.44 (2 H, br s, CH2), 5.02-5.06 (2 H, m, 2 CHO),
3
6.71 (1 H, br s, NH), 7.15 (1 H, t, J = 6.8 Hz, CH), 7.23 (2 H, d, 3J =
6.4 Hz, 2 CH), 7.29 (2 H, d, 3J = 6.4 Hz, 2 CH). 13C NMR (125.7
MHz, CDCl3): δC = 21.4 (2 Me), 21.5 (2 Me), 58.2 (CH2), 70.1
(CHO), 71.1 (CHO), 127.0 (2 CH), 127.8 (CH), 129.4 (2 CH), 136.4
(C), 154.6 (C=O), 156.3 (C=O). MS: m/z (%) = 294 (M+, 1), 235
(51), 207 (35), 120 (24), 103 (89), 91 (100), 87 (76). Anal. Calcd
for C15H22N2O4 (294.35): C, 61.21; H, 7.53; N, 9.52%. Found: C,
61.41; H, 7.68; N, 9.63%.
and/or flame dried glassware under
a pure and dry argon
atmosphere. Mp: Electrothermal-9100 apparatus. IR Spectra:
Shimadzu IR-460 spectrometer. 1H and 13C NMR spectra: Bruker
DRX-500 AVANCE instrument; in CDCl3 at 500.1 and 125.7MHz,
resp; δ in ppm, J in Hz. EI-MS (70 eV): Finnigan-MAT-8430 mass
spectrometer, in m/z. Elemental analyses (C, H, N) were performed
Diisopropyl 1-(4-methylbenzyl)hydrazine-1,2-dicarboxylate (3b)
Colorless solid, mp: 110-112 ˚C; yield: 0.26 g (85%). IR (KBr) (νmax
,
cm-1): 3308, 3066, 2923, 1633, 15391, 1311, 1291, 1083. 1H NMR
(500.1 MHz, CDCl3): δH = 1.21 (6 H, d, J = 6.0 Hz, 2 Me), 1.23 (6
3
with
a Heraeus CHN-O-Rapid analyzer. The results agreed
H, d, 3J = 6.4 Hz, 2 Me), 2.27 (3 H, s, Me), 4.47 (2 H, br s, CH2),
favourably with the calculated values Column chromatography was
performed using Silica gel 60 (particle size 63-200 µm) (Merck, item
number 7734-3). The reactions were monitored by thin layer
chromatography (Silica gel 60, Merck, item number 116835) using
UV light (254 nm) to visualize the course of the reactions.
3
4.98-5.06 (2 H, m, 2 CHO), 6.82 (1 H, br s, NH), 7.16 (2 H, d, J =
6.8 Hz, 2 CH), 7.21 (2 H, d, 3J = 6.8 Hz, 2 CH). 13C NMR (125.7
MHz, CDCl3): δC = 21.9 (2 Me), 22.1 (2 Me), 24.2 (Me), 57.6 (CH2),
69.7 (CHO), 70.5 (CHO), 127.2 (2 CH), 129.1 (2 CH), 135.2 (C),
138.2 (C), 154.5 (C=O), 156.1 (C=O). MS: m/z (%) = 308 (M+, 7),
249 (52), 221 (24), 134 (28), 133 (78), 105 (100), 103 (88), 87
(53). Anal. Calcd for C16H24N2O4 (308.38): C, 62.32; H, 7.84; N,
9.08%. Found: C, 62.49; H, 7.95; N, 9.27%.
General procedure for synthesis of compound 3. An oven-dried
Schlenk tube (25 mL) equipped with a magnetic stir bar was
charged with dialkyl azodicarboxylate (1.0 mmol), Cu2O powder Diisopropyl
1-(3-methylbenzyl)hydrazine-1,2-dicarboxylate
(3c): Colorless solid, mp: 101-103 °C; yield: 0.26 g (83%). IR (KBr)
(0.10 mmol, 14 mg), phen (0.06 mmol, 11 mg), and 4 Å MS (300
mg). The tube was evacuated and backfilled with argon (three
times). DTBP (1.5 mmol) and the benzylic hydrocarbon (2.0 mL)
were added by syringe. The mixture was stirred for appropriate
times (see Table 2) at 110 ˚C. After cooling to room temperature,
the mixture was diluted with EtOAc, filtered, and concentrated
under reduced pressure. The residue was purified with column
chromatography on silica gel (eluent gradient of EtOAc/hexane, 1:8
to 1:4) to give the corresponding products 3 in the yields listed in
Tables 2, 3.
1
(νmax, cm-1): 3271, 3074, 2934, 1635, 1550, 1318, 1110. H NMR
3
(500.1 MHz, CDCl3): δH = 1.20 (6 H, d, J = 6.7 Hz, 2 Me), 1.23 (6
H, d, 3J = 6.2 Hz, 2 Me), 2.34 (3 H, s, Me), 4.59 (2 H, br s, CH2),
3
4.91-4.98 (2 H, m, 2 CHO), 6.85 (1 H, br s, NH), 7.06 (1 H, d, J =
6.6 Hz, CH), 7.25-7.33 (3 H, m, 3 CH). 13C NMR (125.7 MHz,
CDCl3): δC = 21.5 (2 Me), 21.7 (2 Me), 24.7 (Me), 58.1 (CH2), 70.1
(CHO), 70.7 (CHO), 124.6 (CH), 126.2 (CH), 130.3 (CH), 130.5
(CH), 137.8 (C), 139.6 (C), 156.0 (C=O), 156.2 (C=O). MS: m/z (%)
= 308 (M+, 2), 249 (34), 221 (28), 163 (45), 149 (48), 135 (79),
105 (100), 103 (89), 87 (66). Anal. Calcd for C16H24N2O4 (308.38):
C, 62.32; H, 7.84; N, 9.08%. Found: C, 62.43; H, 7.98; N, 9.20%.
Diisopropyl 1-(2-methylbenzyl)hydrazine-1,2-dicarboxylate
(3d): Colorless solid, mp: 90-92 °C; yield: 0.16 g (53%). IR (KBr)
1
(νmax, cm-1): 3256, 3036, 2983, 1691, 1527, 1382, 1257, 1109. H
Conclusion
NMR (500.1 MHz, CDCl3): δH = 1.19 (6 H, d, 3J = 6.2 Hz, 2 Me),
1.25 (6 H, d, 3J = 6.0 Hz, 2 Me), 2.36 (3 H, s, Me), 4.60 (2 H, br s,
CH2), 4.96-5.02 (2 H, m, 2 CHO), 6.71 (1 H, br s, NH), 7.19 (1 H, t,
3J = 6.6 Hz, CH), 7.29-7.32 (2 H, m, 2 CH), 7.34 (1 H, d, 3J = 6.1 Hz,
CH). 13C NMR (125.7 MHz, CDCl3): δC = 21.0 (2 Me), 21.1 (2 Me),
31.4 (Me), 55.3 (CH2), 69.1 (CHO), 69.5 (CHO), 126.5 (CH), 127.1
(CH), 127.4 (CH), 129.7 (CH), 136.4 (C), 142.0 (C), 154.7 (C=O),
156.3 (C=O). MS: m/z (%) = 308 (M+, 3), 249 (23), 221 (36), 148
(52), 135 (68), 105 (100), 103 (90), 87 (79). Anal. Calcd for
C16H24N2O4 (308.38): C, 62.32; H, 7.84; N, 9.08%. Found: C,
62.50; H, 7.94; N, 9.16%.
In summary, we have developed a novel Cu2O promoted approach
for the synthesis of N-Alkyl hydrazides using readily available
starting materials through the benzylic C-H functionalization with
dialkyl azodicarboxylates. The effects of electronic and steric
variations of substrates on reaction outcome have been examined.
The inexpensive and readily available catalyst-ligand-oxidant system
is of practical interest for N-alkylation of azodicarboxylates. The
reaction is completely selective for monoamination and no
compounds arising from diamination of xylene derivatives are
detected by crude GC-MS analysis.
Diisopropyl 1-(3,5-dimethylbenzyl)hydrazine-1,2-dicarboxylate
(3e): Colorless solid, mp: 133-135 °C; yield: 0.29 g (89%). IR (KBr)
1
(νmax, cm-1): 3286, 3008, 2983, 1669, 1519, 1316, 1249, 1107. H
NMR (500.1 MHz, CDCl3): δH = 1.20 (6 H, d, 3J = 6.1 Hz, 2 Me),
1.23 (6 H, d, 3J = 5.8 Hz, 2 Me), 2.33 (6 H, s, 2 Me), 4.49 (2 H, br s,
CH2), 4.94-4.99 (2 H, m, 2 CHO), 6.62 (1 H, br s, NH), 7.13 (2 H, s,
2 CH), 7.28 (1 H, s, CH). 13C NMR (125.7 MHz, CDCl3): δC = 21.9 (2
Me), 22.0 (2 Me), 24.7 (2 Me), 56.4 (CH2), 69.1 (CHO), 69.7
(CHO), 125.6 (2 CH), 130.0 (CH), 139.2 (2 C), 139.8 (C), 154.3
(C=O), 155.2 (C=O). MS: m/z (%) = 322 (M+, 11), 263 (23), 235
(31), 183 (16), 149 (51), 147 (27), 162 (68), 119 (100), 103 (81),
87 (73). Anal.Calcd for C17H26N2O4 (322.41): C, 63.33; H, 8.13; N,
8.69%. Found: C, 63.50; H, 8.29; N, 8.88%.
Acknowledgements
This work was partly supported by the University of Zabol.
Conflicts of interest
There are no conflicts of interest to declare.
4 | New Journal of Chemistry., 2012, 00, 1-3
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DOI: 10.1039/C7NJ04880G
New Journal of Chemistry
ARTICLE
Diisopropyl 1-(4-bromobenzyl)hydrazine-1,2-dicarboxylate (3f): Diisopropyl
Colorless solid, mp: 137-139 °C; yield: 0.28 g (75%). IR (KBr) (νmax,
1-(4-(methoxycarbonyl)benzyl)hydrazine-1,2-
dicarboxylate (3k): Colorless oil, yield: 0.18 g (52%). IR (KBr)
cm-1): 3284, 3034, 2925, 1639, 1524, 1383, 1261, 1108, 596. 1H (νmax, cm-1): 3279, 3040, 2982, 1731, 1690, 1519, 1462, 1384,
1
NMR (500.1 MHz, CDCl3): δH = 1.22 (6 H, d, 3J = 6.1 Hz, 2 Me), 1245, 1111. H NMR (500.1 MHz, CDCl3): δH = 1.21 (6 H, d, 3J =
3
1.24 (6 H, d, 3J = 6.0 Hz, 2 Me), 4.68 (2 H, br s, CH2), 4.96-5.05 (2 6.1 Hz, 2 Me), 1.23 (6 H, d, J = 6.0 Hz, 2 Me), 3.79 (3 H, s, OMe),
3
H, m, 2 CHO), 6.81 (1 H, br s, NH), 7.28 (2 H, d, J = 6.7 Hz, 2 CH), 4.81 (2 H, br s, CH2), 4.97-5.04 (2 H, m, 2 CHO), 6.65 (1 H, br s,
7.62 (2 H, d, 3J = 6.7 Hz, 2 CH). 13C NMR (125.7 MHz, CDCl3): δC = NH), 7.29 (2 H, d, 3J = 6.6 Hz, 2 CH), 8.01 (2 H, d, 3J = 6.6 Hz, 2
20.7 (2 Me), 21.8 (2 Me), 56.3 (CH2), 69.1 (CHO), 70.0 (CHO), CH). 13C NMR (125.7 MHz, CDCl3): δC = 21.9 (2 Me), 23.1 (2 Me),
119.1 (C), 128.9 (2 CH), 131.2 (2 CH), 137.8 (C), 155.3 (C=O), 53.6 (OMe), 59.1 (CH2), 70.3 (CHO), 71.2 (CHO), 127.5 (2 CH),
156.0 (C=O). MS: m/z (%) = 372 (M+, 3), 374 (M++2, 3), 313 (29), 129.7 (C), 131.2 (2 CH), 143.1 (C), 155.7 (C=O), 156.8 (C=O),
285 (19), 212 (43), 199 (67), 169 (100), 103 (82), 87 (76). 168.1 (C=O). MS: m/z (%) = 352 (M+, 1), 293 (14), 265 (23), 251
Anal.Calcd for C15H21BrN2O4 (373.25): C, 48.27; H, 5.67; N, 7.51; (44), 191 (51), 135 (73), 103 (100), 87 (75). Anal.Calcd for
Br, 21.41%. Found: C, 48.44; H, 5.85; N, 7.78; Br, 21.45%. C17H24N2O6 (352.39): C, 57.94; H, 6.87; N, 7.95%. Found: C,
Diisopropyl 1-(3-chlorobenzyl)hydrazine-1,2-dicarboxylate (3g): 58.11; H, 7.02; N, 8.06%.
Colorless solid, mp: 106-108 °C; yield: 0.23 g (70%). IR (KBr) (νmax
,
Diisopropyl 1-(4-methoxybenzyl)hydrazine-1,2-dicarboxylate
cm-1): 3291, 3063, 2983, 1634, 1514, 1380, 1249, 1106, 727. 1H (3l): Colorless solid, mp: 120-122 °C; yield: 0.30 g (92%). IR (KBr)
NMR (500.1 MHz, CDCl3): δH = 1.23 (6 H, d, 3J = 6.1 Hz, 2 Me), (νmax, cm-1): 3279, 3062, 2927, 1628, 1536, 1447, 1328, 1256,
1.25 (6 H, d, 3J = 5.7 Hz, 2 Me), 4.74 (2 H, br s, CH2), 4.95-5.06 (2 1083. 1H NMR (500.1 MHz, CDCl3): δH = 1.19 (6 H, d, 3J = 5.9 Hz, 2
H, m, 2 CHO), 6.76 (1 H, br s, NH), 7.12-7.21 (2 H, m, 2 CH), 7.24- Me), 1.22 (6 H, d, J = 6.1 Hz, 2 Me), 3.90 (3 H, s, OMe), 4.62 (2
3
7.34 (2 H, m, 2 CH), 7.54 (1 H, s, CH). 13C NMR (125.7 MHz, H, br s, CH2), 4.93-4.99 (2 H, m, 2 CHO), 6.65-6.90 (3 H, m, NH
CDCl3): δC = 22.1 (2 Me), 22.3 (2 Me), 59.2 (CH2), 69.1 (CHO), and 2 CH), 7.15 (2 H, d, J = 6.8 Hz, 2 CH). 13C NMR (125.7 MHz,
3
70.5 (CHO), 123.1 (CH), 125.5 (CH), 127.3 (CH), 132.1 (CH), 135.7 CDCl3): δC = 22.1 (2 Me), 22.9 (2 Me), 56.1 (OMe), 57.6 (CH2),
(C), 142.1 (C), 154.2 (C=O), 156.0 (C=O). MS: m/z (%) = 328 (M+, 70.2 (CHO), 71.3 (CHO), 114.7 (2 CH), 127.9 (2 CH), 129.3 (C),
8), 269 (23), 241 (37), 183 (16), 167 (68), 155 (45), 125 (100), 103 159.4 (C), 155.3 (C=O), 156.1 (C=O). MS: m/z (%) = 324 (M+, 15),
(91), 87 (84). Anal.Calcd for C15H21ClN2O4 (328.79): C, 54.80; H, 265 (16), 237 (28), 163 (72), 121 (100), 103 (89), 87 (84).
6.44; N, 8.52; Cl, 10.78%. Found: C, 54.97; H, 6.65; N, 8.58; Cl, Anal.Calcd for C16H24N2O5 (324.38): C, 59.24; H, 7.46; N, 8.64%.
10.86%. Found: C, 59.41; H, 7.63; N, 8.79%.
Diisopropyl 1-(4-iodobenzyl)hydrazine-1,2-dicarboxylate (3h): Diisopropyl 1-(1-phenylethyl)hydrazine-1,2-dicarboxylate (3m):
Colorless solid, mp: 144-146 °C; yield: 0.31 g (74%). IR (KBr) (νmax
,
Colorless solid, mp: 81-83 °C; yield: 0.20 g (64%). IR (KBr) (νmax,
1
cm-1): 3286, 3041, 2926, 1639, 1564, 1414, 1285, 1079, 539. 1H cm-1): 3273, 3051, 2984, 1639, 1511, 1382, 1250, 1104. H NMR
NMR (500.1 MHz, CDCl3): δH = 1.19 (6 H, d, 3J = 5.7 Hz, 2 Me), (500.1 MHz, CDCl3): δH = 1.20 (6 H, d, J = 6.2 Hz, 2 Me), 1.25 (6
3
1.23 (6 H, d, 3J = 6.2 Hz, 2 Me), 4.53 (2 H, br s, CH2), 5.04-5.10 (2 H, d, 3J = 6.4 Hz, 2 Me), 1.62 (3 H, d, 3J = 5.8 Hz, Me), 4.90-4.98 (2
3
H, m, 2 CHO), 6.91 (1 H, br s, NH), 7.49 (1 H, d, J = 6.8 Hz, CH), H, m, 2 CHO), 5.11 (1 H, q, 3J = 5.8 Hz, 2 Me), 6.73 (1 H, br s, NH),
3
7.72 (1 H, d, J = 6.8 Hz, CH). 13C NMR (125.7 MHz, CDCl3): δC = 7.26-7.35 (5 H, m, 5 CH). 13C NMR (125.7 MHz, CDCl3): δC = 17.2
21.1 (2 Me), 21.3 (2 Me), 59.1 (CH2), 70.2 (CHO), 71.1 (CHO), (Me), 22.1 (2 Me), 22.5 (2 Me), 64.2 (CH), 70.3 (CHO), 71.1
98.0 (C), 130.1 (2 CH), 136.2 (C), 138.3 (2 CH), 154.2 (C=O), 156.1 (CHO), 126.1 (CH), 126.3 (2 CH), 128.6 (2 CH), 142.4 (C), 154.6
(C=O). MS: m/z (%) = 420 (M+, 1), 361 (21), 333 (17), 318 (35), (C=O), 156.1 (C=O). MS: m/z (%) = 308 (M+, 6), 249 (18), 221 (25),
259 (78), 217 (100), 103 (85), 87 (74). Anal.Calcd for C15H21IN2O4 147 (56), 105 (91), 103 (82), 87 (67), 77 (100). Anal. Calcd for
(420.25): C, 42.87; H, 5.04; N, 6.67; I, 30.20%. Found: C, 43.03; H, C16H24N2O4 (308.38): C, 62.32; H, 7.84; N, 9.08%. Found: C,
5.21; N, 6.82; I, 30.27%.
Diisopropyl
62.48; H, 7.97; N, 9.220%.
1-(4-(methylthio)benzyl)hydrazine-1,2- Diisopropyl 1-(1-phenylpropyl)hydrazine-1,2-dicarboxylate
dicarboxylate (3i): Colorless solid, mp: 111-113 °C; yield: 0.16 g (3n): Colorless solid, mp: 83-85 °C; yield: 0.20 g (62%). IR (KBr)
(48%). IR (KBr) (νmax, cm-1): 3282, 3065, 2926, 1632, 1511, 1380, (νmax, cm-1): 3284, 3041, 2985, 1639, 1514, 1458, 1380, 1254,
1
3
1258, 1107, 973. 1H NMR (500.1 MHz, CDCl3): δH = 1.21 (6 H, d, 3J 1107. H NMR (500.1 MHz, CDCl3): δH = 0.89 (3 H, t, J = 5.7 Hz,
= 5.7 Hz, 2 Me), 1.23 (6 H, d, 3J = 5.8 Hz, 2 Me), 2.71 (3 H, s, Me), Me), 1.20 (6 H, d, J = 6.1 Hz, 2 Me), 1.26 (6 H, d, J = 6.3 Hz, 2
4.59 (2 H, br s, CH2), 4.93-4.99 (2 H, m, 2 CHO), 6.68 (1 H, br s, Me), 1.97-2.08 (2 H, m, CH2), 4.76-4.84 (1 H, m, CH), 5.01-5.09 (2
NH), 7.23 (2 H, d, 3J = 6.9 Hz, 2 CH), 7.34 (2 H, d, 3J = 6.9 Hz, 2 H, m, 2 CHO), 6.60 (1 H, br s, NH), 7.20-7.35 (5 H, m, 5 CH). 13C
CH). 13C NMR (125.7 MHz, CDCl3): δC = 15.2 (Me), 21.0 (2 Me), NMR (125.7 MHz, CDCl3): δC = 11.1 (Me), 21.6 (2 Me), 21.8 (2
22.4 (2 Me), 56.2 (CH2), 70.1 (CHO), 70.9 (CHO), 126.2 (2 CH), Me), 31.8 (CH2), 70.1 (CHO), 70.6 (CHO), 79.2 (CH), 126.7 (CH),
129.0 (2 CH), 134.3 (C), 142.6 (C), 154.8 (C=O), 156.1 (C=O). MS: 127.3 (2 CH), 129.8 (2 CH), 141.9 (C), 154.2 (C=O), 156.1 (C=O).
m/z (%) = 340 (M+, 1), 297 (12), 280 (17), 239 (31), 180 (56), 152 MS: m/z (%) = 322 (M+, 5), 293 (11), 262 (20), 221 (38), 161 (48),
(22), 138 (100), 123 (61), 91 (45). Anal.Calcd for C16H24N2O4S 119 (78), 103 (78), 87 (76), 77(100). Anal. Calcd for C17H26N2O4
(340.44): C, 56.45; H, 7.11; N, 8.23; S, 9.42%. Found: C, 56.63; H, (322.41): C, 63.33; H, 8.13; N, 8.69%. Found: C, 63.56; H, 8.31; N,
3
3
7.24; N, 8.42; Br, 9.52%.
Diisopropyl 1-([1,1'-biphenyl]-3-ylmethyl)hydrazine-1,2- Diisopropyl 1-benzhydrylhydrazine-1,2-dicarboxylate (3o):
8.82%.
dicarboxylate (3j): Colorless solid, mp: 135-137 °C; yield: 0.27 g Colorless solid, mp: 161-163 °C; yield: 0.20 g (55%). IR (KBr) (νmax
,
(65%). IR (KBr) (νmax, cm-1): 3297, 3062, 2927, 1628, 1536, 1447, cm-1): 3279, 3055, 2984, 1637, 1508, 1462, 1382, 1249, 1181,
1
1328, 1256, 1083, 846. H NMR (500.1 MHz, CDCl3): δH = 1.21 (6 1103. 1H NMR (500.1 MHz, CDCl3): δH = 1.23 (6 H, d, 3J = 6.1 Hz, 2
3
H, d, 3J = 6.1 Hz, 2 Me), 1.25 (6 H, d, 3J = 6.3 Hz, 2 Me), 4.69 (2 H, Me), 1.25 (6 H, d, J = 6.0 Hz, 2 Me), 4.95-5.02 (2 H, m, 2 CHO),
br s, CH2), 5.01-5.09 (2 H, m, 2 CHO), 6.92 (1 H, br s, NH), 7.35- 6.32 (1 H, s, CH), 6.87 (1 H, br s, NH), 7.20-7.61 (10 H, m, 10 CH).
7.80 (8 H, m, 8 CH), 7.94 (1 H, s, CH). 13C NMR (125.7 MHz, 13C NMR (125.7 MHz, CDCl3): δC = 21.8 (2 Me), 22.0 (2 Me), 69.7
CDCl3): δC = 22.1 (2 Me), 22.4 (2 Me), 60.1 (CH2), 70.1 (CHO), (CHO), 70.5 (CHO), 72.1 (CH), 125.5 (CH), 125.7 (CH), 126.0 (2
70.5 (CHO), 124.2 (CH), 126.6 (CH), 127.3 (CH), 128.1 (2 CH), CH), 126.3 (2 CH), 128.7 (2 CH), 128.8 (2 CH), 143.1 (C), 143.2 (C),
129.3 (2 CH), 130.1 (CH), 132.4 (CH), 141.2 (C), 142.8 (C), 143.5 154.9 (C=O), 156.1 (C=O). MS: m/z (%) = 370 (M+, 1), 311 (15),
(C), 155.7 (C=O), 156.4 (C=O). MS: m/z (%) = 370 (M+, 3), 310 283 (30), 269 (45), 209 (608), 167 (100), 103 (87), 91 (67), 77
(18), 268 (21), 209 (47), 167 (64), 91 (38), 77 (100). Anal.Calcd (86). Anal. Calcd for C21H26N2O4 (370.45): C, 68.09; H, 7.07; N,
for C21H26N2O4 (370.45): C, 68.09; H, 7.07; N, 7.56%. Found: C, 7.56%. Found: C, 68.28; H, 7.25; N, 7.69%.
68.29; H, 7.25; N, 7.64%.
This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C7NJ04880G
ARTICLE
New Journal of Chemistry
Diisopropyl 1-(4-ethylbenzyl)hydrazine-1,2-dicarboxylate (3p): H, s, MeO), 4.18-4.35 (4 H, m, 2 CH2), 4.57 (2 H, br s, CH2), 6.67-
Colorless solid, mp: 113-115 °C; yield: 0.16 g (51%). IR (KBr) (νmax,
7.10 (3 H, m, NH and 2 CH), 7.19 (2 H, d, 3J = 6.4 Hz, 2 CH). 13C
cm-1): 3384, 3065, 2933, 1666, 1549, 1451, 1376, 1253, 1166, NMR (125.7 MHz, CDCl3): δC = 15.0 (Me), 15.3 (Me), 57.4 (MeO),
1089, 1027. 1H NMR (500.1 MHz, CDCl3): δH = 0.98 (3 H, t, 3J = 5.6 58.1 (CH2), 63.1 (CH2O), 63.5 (CH2O), 114.1 (2 CH), 129.3 (2 CH),
Hz, Me), 1.21 (6 H, d, J = 6.1 Hz, 2 Me), 1.23 (6 H, d, J = 6.0 Hz, 130.9 (C), 154.6 (C=O), 155.7 (C=O), 160.5 (C). MS: m/z (%) = 296
3
3
3
2 Me), 2.95 (2 H, q, J = 5.8 Hz, CH2), 4.67 (2 H, br s, CH2), 4.96- (M+, 15), 251 (22), 223 (28), 209 (44), 209 (44), 163 (51), 121
5.04 (2 H, m, 2 CHO), 6.74 (1 H, br s, NH), 7.15 (2 H, d, 3J = 6.9 Hz, (100), 89 (85), 74 (61). Anal. Calcd for C14H20N2O5 (296.32): C,
2 CH), 7.27 (2 H, d, 3J = 6.9 Hz, 2 CH). 13C NMR (125.7 MHz, 56.75; H, 6.80; N, 9.45%. Found: C, 56.93; H, 6.98; N, 9.61%.
CDCl3): δC = 17.2 (Me), 21.1 (2 Me), 21.5 (2 Me), 37.3 (CH2), 57.1 Dicyclohexyl
1-benzylhydrazine-1,2-dicarboxylate
(3u):
,
(CH2), 69.1 (CHO), 70.8 (CHO), 128.1 (2 CH), 129.7 (2 CH), 135.0 Colorless solid, mp: 167-169 °C; yield: 0.31 g (84%). IR (KBr) (νm1ax
(C), 140.3 (C), 154.8 (C=O), 156.3 (C=O). MS: m/z (%) = 322 (M+, cm-1): 3276, 3043, 2978, 1652, 1563, 1471, 1352, 1234, 1067. H
11), 263 (21), 235 (23), 221 (46), 161 (67), 119 (100), 103 (87), 87 NMR (500.1 MHz, CDCl3): δH = 1.13-1.83 (20 H, m, 10 CH2), 4.50
(66). Anal. Calcd for C17H26N2O4 (322.41): C, 63.33; H, 8.13; N, (2 H, br s, CH2),4.85-4.96 (2 H, m, 2 CH), 6.21 (1 H, br s, NH), 7.29
3
8.69%. Found: C, 63.57; H, 8.29; N, 8.84%.
(2 H, d, 3J = 6.7 Hz, 2 CH), 7.35 (1 H, d, J = 6.7 Hz, CH), 7.42 (2 H,
Diisopropyl 1-(1-(p-tolyl)ethyl)hydrazine-1,2-dicarboxylate (3p d, 3J = 6.6 Hz, 2 CH). 13C NMR (125.7 MHz, CDCl3): δC = 24.8 (2
′): Colorless solid, mp: 103-105 °C; yield: 0.09 g (27%). IR (KBr) CH2), 25.3 (2 CH2), 29.1 (CH2), 29.2 (CH2), 33.8 (2 CH2), 34.2 (2
(νmax, cm-1): 3299, 3040, 2926, 1624, 1538, 1449, 1332, 1249, CH2), 58.1 (CH2), 74.3 (CH), 74.8 (CH), 126.5 (CH), 127.5 (2 CH),
1173, 1024. 1H NMR (500.1 MHz, CDCl3): δH = 1.19 (6 H, d, J = 129.2 (2 CH), 136.1 (C), 158.1 (C=O), 159.2 (C=O). MS: m/z (%) =
3
3
3
5.9 Hz, 2 Me), 1.21 (6 H, d, J = 6.2 Hz, 2 Me), 1.72 (3 H, d, J = 374 (M+, 4), 283 (26), 282 (47), 274 (28), 232 (39), 133 (57), 91
6.6 Hz, Me), 2.27 (3 H, s, Me), 4.90-4.98 (2 H, m, 2 CHO), 5.15 (1 (100), 77 (43), 83 (67). Anal. Calcd for C21H30N2O4 (374.48): C,
H, q, 3J = 6.6 Hz, CH), 6.78 (1 H, br s, NH), 7.11 (2 H, d, 3J = 6.2 Hz, 67.35; H, 8.08; N, 7.48%. Found: C, 67.56; H, 8.27; N, 7.60%.
2 CH), 7.30 (2 H, d, 3J = 6.2 Hz, 2 CH). 13C NMR (125.7 MHz, Di-tert-butyl
1-benzylhydrazine-1,2-dicarboxylate
(3v):
CDCl3): δC = 17.8 (Me), 22.1 (2 Me), 22.5 (2 Me), 24.7 (Me), 70.1 Colorless solid, mp: 104-106 °C; yield: 0.25 g (76%). IR (KBr) (νm1ax
,
(CHO), 70.3 (CHO), 74.8 (CH), 127.1 (2 CH), 129.5 (2 CH), 137.1 cm-1): 3295, 3051, 2978, 1648, 1563, 1462, 1331, 1213, 1052. H
(C), 140.5 (C), 154.7 (C=O), 155.8 (C=O). MS: m/z (%) = 322 (M+, NMR (500.1 MHz, CDCl3): δH = 1.49 (9 H, s, 3 Me), 1.52 (9 H, s, 3
7), 263 (22), 235 (28), 221 (16), 161 (53), 119 (100), 103 (89), 87 Me), 4.45 (2 H, br s, CH2), 6.49 (1 H, br s, NH), 7.24-7.33 (3 H, m,
(72). Anal. Calcd for C17H26N2O4 (322.41): C, 63.33; H, 8.13; N, 3 CH), 7.37 (2 H, d, 3J = 6.7 Hz, 2 CH). 13C NMR (125.7 MHz,
8.69%. Found: C, 63.54; H, 8.28; N, 8.77%. CDCl3): δC = 30.8 (3 Me), 31.1 (3 Me), 59.4 (CH2), 83.7 (C), 83.9
Diethyl 1-benzylhydrazine-1,2-dicarboxylate (3q): Colorless (CH), 126.7 (CH), 129.7 (2 CH), 130.9 (2 CH),137.5 (C), 157.8
solid, mp: 87-89 °C; yield: 0.22 g (82%). IR (KBr) (νmax, cm-1): (C=O), 160.4 (C=O). MS: m/z (%) = 322 (M+, 1), 265 (18), 248 (23),
3297, 3064, 2944, 1659, 1552, 1451, 1368, 1284, 1167, 1088. H 221 (36), 206 (40), 133 (57), 91 (100), 77 (38), 57 (83). Anal.
1
NMR (500.1 MHz, CDCl3): δH = 1.22-1.34 (6 H, m, 2 Me), 4.22- Calcd for C17H26N2O4 (322.41): C, 63.33; H, 8.13; N, 8.69%.
4.31 (4 H, m, 2 CH2), 4.67 (2 H, br s, CH2), 6.65 (1 H, br s, NH), Found: C, 63.54; H, 8.28; N, 8.78%.
7.25-7.36 (5 H, m, 5 CH). 13C NMR (125.7 MHz, CDCl3): δC = 18.1 Diphenyl 1-benzylhydrazine-1,2-dicarboxylate (3w): Colorless
(Me), 18.3 (Me), 58.9 (CH2), 64.1 (CH2O), 64.9 (CH2O), 125.3 solid, mp: 153-155.5 °C; yield: 0.33 g (90%). IR (KBr) (νmax, cm-1):
1
(CH), 126.1 (2 CH), 129.1 (2 CH), 137.3 (C), 156.1 (C=O), 156.6 3266, 3063, 3030, 2954, 1672, 1555, 1442, 1308, 1246, 1024. H
(C=O). MS: m/z (%) = 266 (M+, 14), 221 (19), 193 (24), 179 (48), NMR (500.1 MHz, CDCl3): δH = 4.34 (2 H, br s, CH2), 6.61 (1 H, br
133 (67), 91 (100), 89 (89), 74 (58). Anal. Calcd for C13H18N2O4 s, NH), 7.16-7.51 (15 H, m, 15 CH). 13C NMR (125.7 MHz, CDCl3):
(266.30): C, 58.63; H, 6.81; N, 10.52%. Found: C, 58.85; H, 6.99; δC = 62.7 (CH2), 118.5 (2 CH), 118.9 (2 CH), 124.7 (CH), 124.9
N, 10.66%. (CH), 125.1 (CH), 128.3 (2 CH), 128.5 (2 CH), 129.3 (2 CH), 129.4
Diethyl 1-(4-methylbenzyl)hydrazine-1,2-dicarboxylate (3r): (2 CH), 137.8 (C), 154.2 (C), 154.4 (C), 156.7 (C=O), 158.2 (C=O).
Colorless solid, mp: 100-102 °C; yield: 0.23 g (83%). IR (KBr) (νmax
,
MS: m/z (%) = 362 (M+, 7), 285 (14), 269 (31), 226 (21), 136 (47),
cm-1): 3268, 3072, 2927, 1650, 1551, 1427, 1365, 1228, 1118, 133 (68), 91 (100), 77 (79), 54 (43). Anal. Calcd for C21H18N2O4
1051. 1H NMR (500.1 MHz, CDCl3): δH = 1.25-1.33 (6 H, m, 2 Me), (362.39): C, 69.60; H, 5.01; N, 7.73%. Found: C, 69.85; H, 5.25; N,
2.28 (3 H, s, Me), 4.20-4.27 (4 H, m, 2 CH2), 4.61 (2 H, br s, CH2), 7.95%.
6.58 (1 H, br s, NH), 7.14 (2 H, d, 3J = 6.7 Hz, 2 CH), 7.28 (2 H, d, 3J
= 6.7 Hz, 2 CH). 13C NMR (125.7 MHz, CDCl3): δC = 14.4 (Me), 14.5
(Me), 23.7 (Me), 58.1 (CH2), 62.3 (CH2O), 62.8 (CH2O), 127.2 (2 1 V. Soni, S . M. Khake, B. Punji, ACS Catal., 2017, 7, 4202.
CH), 128.7 (2 CH), 135.1 (C), 137.9 (C), 155.2 (C=O), 156.5 (C=O). 2 F. Shahsavaria, A. Abbasi, M. Ghazanfarpour-Darjani, S. M.
MS: m/z (%) = 280 (M+, 7), 235 (18), 207 (34), 193 (41), 147 (57), Ghafelebashi, M. Daftari-Besheli, Synlett., 2017, 28, 1646.
105 (100), 89 (81), 74 (57). Anal. Calcd for C14H20N2O4 (280.32): 3 R. Vanjari, K. N. Singh, Chem. Soc. Rev., 2015, 44, 8062.
C, 59.99; H, 7.19; N, 9.99%. Found: C, 60.18; H, 7.36; N, 10.16%. 4 R. Hili, A. K. Yudin, Nat. Chem. Biol., 2006, 2, 284.
Diethyl 1-(3,5-dimethylbenzyl)hydrazine-1,2-dicarboxylate (3s) 5 J. L. Opgrande, E. Brown, M. Hesser, J. Andrews, In Kirk-
Colorless solid, mp: 121-123 °C; yield: 0.27 g (91%). IR (KBr) (νm1ax
,
Othmer Encyclopedia of Chemical Technology; John Wiley &
cm-1): 3312, 3041, 2933, 1628, 1546, 1460, 1320, 1267, 1056. H Sons, Inc.: Hoboken, NJ, 2000.
NMR (500.1 MHz, CDCl3): δH = 1.23-1.37 (6 H, m, 2 Me), 2.25 (6 6 V. Bagchi, P. Paraskevopoulou, P. Das, L. Chi, Q. Wang,
H, s, 2 Me), 4.21-4.30 (4 H, m, 2 CH2), 4.54 (2 H, br s, CH2), 6.84 A. Choudhury, J. S. Mathieson, L. Cronin, D. B. Pardue,
(1 H, br s, NH), 7.13 (2 H, s, 2 CH), 7.19 (1 H, s, CH). 13C NMR T. R. Cundari, G. Mitrikas, Y. Sanakis, P. Stavropoulos, J. Am.
(125.7 MHz, CDCl3): δC = 14.1 (Me), 14.2 (Me), 25.1 (2 Me), 56.3 Chem. Soc., 2014, 136, 11362.
(CH2), 62.1 (CH2O), 62.4 (CH2O), 126.0 (2 CH), 130.4 (CH), 139.7 7 L. Maestre, W. M. C. Sameera, M. M. Díaz-Requejo, F.
(2 C), 142.1 (C), 155.6 (C=O), 156.3 (C=O). MS: m/z (%) = 294 (M+, Maseras, P. J. J. Pérez, J. Am. Chem. Soc., 2013, 135, 1338.
11), 249 (16), 221 (27), 207 (46), 161 (57), 119 (100), 89 (71), 74 8 E. R. King, E. T. Hennessy, T. A. Betley, J. Am. Chem. Soc.,
(52). Anal. Calcd for C15H22N2O4 (294.35): C, 61.21; H, 7.53; N, 2011, 133, 4917.
9.52%. Found: C, 61.38; H, 7.70; N, 9.69%.
Diethyl 1-(4-methoxybenzyl)hydrazine-1,2-dicarboxylate (3t)
9 D. A. Powell, H. Fan, J. Org. Chem., 2010, 75, 2726.
10 A. Wang, N. J. Venditto, J. W. Darcy, M. H. Emmert,
Organometallics., 2017, 36, 1259.
Colorless solid, mp: 108-110 °C; yield: 0.26 g (89%). IR (KBr) (νm1ax
,
cm-1): 3283, 3072, 2963, 1658, 1541, 1488, 1368, 1221, 1088. H
NMR (500.1 MHz, CDCl3): δH = 1.21-1.36 (6 H, m, 2 Me), 3.79 (3
6 | New Journal of Chemistry., 2012, 00, 1-3
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100% hexanes to 35% ethyl acetate in hexanes afforded the
above regioisomeric products (the column length and diameter
were 1.5 m and 12 mm, respectively. Silica gel 60 (15-40 µm)
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