Convenient methodology for the synthesis of trialkylhydrazines

Article abstract of DOI:10.1080/00397910902738120

A convenient methodology, based on the addition of organolithium compounds to N-nitrosamines, was developed for the synthesis of substituted hydrazones and trialkyl hydrazines. The reaction is very sensitive to the reaction conditions, particularly the [R

Full text of DOI:10.1080/00397910902738120

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Convenient Methodology
for the Synthesis of
Trialkylhydrazines
Alvaro J. Vázquez a , Cristian Rodríguez a & N.
Sbarbati Nudelman a
a Department of Organic Chemistry, Facultad de
Ciencias Exactas y Naturales, Universidad de Buenos
Aires, Ciudad Universitaria, Buenos Aires, Argentina
Published online: 16 Oct 2009.
To cite this article: Alvaro J. Vázquez , Cristian Rodríguez & N. Sbarbati Nudelman
(2009) Convenient Methodology for the Synthesis of Trialkylhydrazines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:22, 3958-3972, DOI: 10.1080/00397910902738120
To link to this article: http://dx.doi.org/10.1080/00397910902738120
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Synthetic Communications1, 39: 3958–3972, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902738120
Convenient Methodology for the
Synthesis of Trialkylhydrazines
ꢀ
´
Alvaro J. Vazquez, Cristian Rodrıguez, and N. Sbarbati Nudelman
Department of Organic Chemistry, Facultad de Ciencias Exactas y
Naturales, Universidad de Buenos Aires, Ciudad Universitaria,
Buenos Aires, Argentina
Abstract: A convenient methodology, based on the addition of organolithium
compounds to N-nitrosamines, was developed for the synthesis of substituted
hydrazones and trialkyl hydrazines. The reaction is very sensitive to the reaction
conditions, particularly the [RLi]–[nitrosamine] ratio. For molar ratios of 1–1.2,
an almost quantitative conversion to the N ¼ O bond addition products (i.e.,
alkylhydrazones) can be obtained in very good yields, with any remaining nitro-
samine. Using greater molar ratios (in the range of 3–5), a second addition occurs,
and branched trialkyl hydrazines are obtained, in good yields, with variable
amounts of hydrazone remaining. Substituted hydrazines are known to have use-
ful commercial applications and remarkable biological activities. A wide diversity
of trialkyl hydrazines could be synthesized by using two different organolithiums.
Keywords: Addition to the N ¼ O bond, hydrazines, hydrazones, nitrosamines,
organolithiums
INTRODUCTION
Hydrazine and its derivatives are of considerable technical and
commercial importance,[1,2] and they are receiving renewed interest
because of the recent discovery of their remarkable biological activities.
Received September 5, 2008.
Address correspondence to N. Sbarbati Nudelman, Department of Organic
Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos
Aires, Pab. II, P. 3, Ciudad Universitaria, 1428 Buenos Aires, Argentina. E-mail:
nudelman@qo.fcen.uba.ar
3958

Convenient Synthesis of Trialkylhydrazines
3959
These derivatives are wellknown as pesticides, drugs, amino acid
precursors, and synthetic building blocks for heterocyclic synthesis.[3]
Substituted hydrazines are key components of azapeptides, a type of pep-
tidomimetics, in which one or more of the amino acid residues have been
replaced by monomers with nitrogen in the position of the chiral carbons.
Hydrazine-based peptidomimetics are found to be potent agents against
hepatitis, AIDS, and SARS.[4,5] Isoniacid, a pyiridine hydrazide, is the
active compound in many drugs used against tuberculosis; several hydra-
zine derivatives have been shown to be effective for Parkinson’s disease
and hypertension.[1]
Because of the remarkable interest in substituted hydrazines, a large
number of synthetic procedures have been developed.[1,6] Many attempts
at alkylation of free hydrazine gave poor results; generally mixtures are
produced, with yields seldom exceeding 40%. To avoid multiple alkyl-
ation, some systematic synthetic methods have been developed recently
using protective group methodology. Nowadays, a large number of
convenient protecting groups for amino functions are available,[7] but this
strategy demands many steps (at least two extra steps) to obtain the end
product.[8,9] Though the purity and total yield of the products are often
greater and purification steps are simpler, the protective group methodol-
ogy uses several steps, consumes more energy, and produces significant
residues; therefore, development of cleaner synthetic methods are
desired.[10,11] A polystyrene sulfonic acid–catalyzed greener synthesis of
hydrazones was recently reported.[12] Tandem reactions are considered
among the most efficient and economical synthetic strategies,[13] and the
amounts of solvents, reagents, and energy are significant decreased as
compared with stepwise reactions.[14,15] The present article describes a
convenient, direct methodology for the preparation of trialkyl hydrazines
based on the tandem addition of organolithium compounds to the double
bond of dialkylnitrosamines, producing substituted hydrazones, which
in a one-pot, one-step reaction can be transformed into trialkylhydrazines
by the tandem addition of the same or another organolithium reagent.
On the other hand, nitrosamines can be synthesized by the NO insertion
into the N-Li bond of lithium amides.[16]
RESULTS AND DISCUSSION
Synthesis of Hydrazones
New reactions on nitrosamines are being actively studied, especially their
relationship with carcinogenetic and mutagenic properties[17]; recent
studies showed that they are mainly mutagenic through methylation of

ꢀ
A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
´
3960
Figure 1. R1: (a) H; (b) Et; (c) n-Pr; and (d) n-Bu; 69–93% yield.
DNA.[18] There is special concern about the important roles that
environmental nitrosamines play in the etiology of human cancer.[19]
The nitrosamine found in cigarette smoke induces lung tumors in mice[20]
and esophageal and gastroduodenal cancer in animals.[21,22] Nitrosamines
also have been found in several foods and beverages.[9,23]
The synthetic methodology herewith described is based on the
reaction of organolithium compounds, R1CH2Li, with N-dialkyl-
nitrosamines. Namely, N-nitrosodicyclohexylamine, 1, in tetrahydrofuran
(THF), leads to the production of hydrazones, 2, as indicated in the Fig. 1.
Mechanistic studies on the addition of RLi on a C ¼ O bond are
abundant in the literature, but few involve bonds to nitrogen atoms.[24]
The first adduct between an amine and a carbonyl derivative was isolated
a few years ago.[25] By 13C NMR, we characterized the first adduct
between a formamide and R2NLi,[26] and a more complex dilithiated
adduct was later characterized.[27]
The reaction described in this article is extremely sensitive to the
reaction conditions. The reaction can be carried out at room temperature;
in most cases the reaction time is very short (5 min, approx.). One mmol
of 1 was dissolved in 2 ml of THF, and the organolithium reagent was
added in a [R1CH2Li]–[1] ¼ 1.05:1.2 molar ratio. The concentration of
organolithium was in the range of 0.5–1.5 M (approx.) in n-hexane solu-
tion. In the case of MeLi (which is less soluble in hexane), a 1 M THF
solution was used, and a longer reaction time (2 h) was required. In gen-
eral terms, the reaction is very clean, no nitrosamine remains, and good
to high yields (69–93%) are obtained in short reaction times.
Synthesis of Trialkylhydrazines
In the reaction of 1 with RLi, under the conditions described previously
but using a high excess of RLi (3–5 eq.), an in situ second addition occurs
at the N ¼ C bond of intermediate 2, and a trialkyl hydrazine, 3, is
formed (Fig. 2).
To the best of our knowledge, few studies have dealt with the addi-
tion of RLi on a carbon–nitrogen double bond. We observed that the

Convenient Synthesis of Trialkylhydrazines
3961
Figure 2. R1: (a) H; (b) Et; (c) n-Pr; and (d) n-Bu.
addition to the N ¼ C bond is slower than to the N ¼ O. To systematize
results, in all cases the reactions were carried out for 2 h at room tempera-
ture. (Attempts to carry out the reaction at lower temperatures were not
satisfactory.) The results are shown in Table 1. As can be observed, good
yields of 3 were obtained for n-PrLi and n-BuLi (entries b and c). With
n-C5H11Li, instead, lower yields of 3d were obtained, and significant
amounts of 2d remained; likely the greater steric hindrance of the
n-pentyl groups is responsible for the lower reactivity. In the reactions
with MeLi, normal addition to form the hydrazone of formaldehyde
(2a) occurred, but when a second molecule of MeLi was added, loss of
the elements of lithium hydride spontaneously occured and the hydra-
zone of acetaldehyde was isolated as the main product instead of the
expected trialkylhydrazine. A similar LiH elimination was observed in
the reaction of diethylnitrosamine with MeLi, for which a tiny amount
(<2%) of Et2NN ¼ CHCH3 was formed.[28]
The formation of 2c (starting from 1, and adding n-BuLi) is very fast
(occurs in a few seconds, even at 0ꢀC), The hydrazone 2c formed in situ
reacts with more n-BuLi, affording 3c (Fig. 3). When some remaining
hydrazones are observed, the yields of hydrazines 3 can be increased by
adding more n-BuLi after the reaction has advanced (i.e., when some
remaining 2 was still present in the reaction mixture).
Table 1. Reaction of dicyclohexylnitrosamine, 1, with RLi (in high excess) in
THF, at room temperaturea
Entry
RLi
[RLi]:[1]
R1
Yield of 2b%
Yield of 3c%
a
b
c
MeLi
n-PrLi
n-BuLi
n-C5H11Li
3
4
5
8
H
Et
n-Pr
n-Bu
28
36d,e
77
75
61e
9.3
2.4
13
d
aTemp. 20–25ꢀC. Reaction time 2 h.
b2 ¼ (c-C6H11)2NN ¼ CHR1.
c3 ¼ (c-C6H11)2NNH-CH(R1)R.
dMain product ¼ (c-C6H11)2NN ¼ CHCH3.
eLateral products in minor yields.

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A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
´
3962
Figure 3. Reaction carried out with n-BuLi in high excess at r.t.
In some cases, by-products are produced in small amounts. Namely,
dicyclohexylamine, 4; N-cyclohexylidenecyclohexylamine, 5; and N,N,N0-
dicyclohexylalkylhydrazines, 6 were found in poor variable yields (3–5%);
they are easily identifiable by gas chromatography.
Synthesis of Several Trialkylhydrazines 7
The reaction of 1 was carried out using two different organolithiums with the
purpose of obtaining several branched hydrazines, 7, as shown in Fig. 4.
For the addition of the first organolithium, the procedure described in
the first part for the hydrazone synthesis was followed: addition of a slight
excess of R1CH2Li and short reaction times (a few minutes, except in the
case of MeLi, which required longer times). For the addition of the second
organolithium, R2Li, a greater excess of the reagent (4–5 equiv.) and longer
reaction times (2 h) were needed. As can be observed in Table 2, the yields
of 7 are good, and little unreacted 2 remained; for the case of n-C5H11Li,
the yields are less than in the other cases, as expected. On the other hand,
it can be observed that by using PhLi, the hydrazine 7 h is not obtained
(even when the reaction was carried out at 50ꢀC), likely as a consequence
of the poor reactivity of PhLi compared to the alkyllithium compounds.
Though the reaction of organolithiums with the N ¼ O bond is much
less known than the synthetically very useful addition of RLi to C ¼ O
bonds, the efficient formation of hydrazones shown in the present study
can be interpreted by an addition mechanism.
Addition of organolithium to C ¼ N bond is less frequent than
to C ¼ O bond, though it is a well-known reaction. Nevertheless, in the
present conditions, addition of a second molecule of RLi to C ¼ N is
Figure 4. Sequence of reaction of compound 1 with two different organolithiums
at r.t.

Convenient Synthesis of Trialkylhydrazines
3963
Table 2. Reaction of dicyclohexylnitrosamine, 1, with two different organo-
lithium compounds in THF, at room temperaturea
Entry
RLib
R2Li
[R2Li]:[1] R1 Yield of 2c % Yield of 7d %
a
b
c
d
e
f
g
h
MeLi
n-BuLi
n-BuLi
n-C5H11Li
n-PrLi
4
5
5
5
5
4
4
3
H
Et
Et
n-Pr
n-Bu
n-Pr
n-Bu
n-Pr
0.8
4.6
64e
69
59
64
69f
68
63
––
n-PrLi
n-PrLi
n-BuLi
n-C5H11Li n-PrLi
n-BuLi
n-C5H11Li n-BuLi
2.0 (2b)
8.6 (2c)
9.8 (2d)
4.9 (2c)
6.7 (2d)
61 (2c)
n-C5H11Li
n-BuLi
PhLi
aReaction time: 2 h.
b[RLi]:[1]: 1.05–1.2.
c2 ¼ (c-C6H11)2NN ¼ CHR1.
d7 ¼ (c-C6H11)2NNH-CHR1R2.
e15% of 3c observed.
fThis compound is called 3c in Table 1.
much more difficult than to N ¼ O. It takes much longer and never goes
to completion. Similar results were recently reported for the addition of
a-lithio methoxyallene to some hydrazones: surprisingly, no reaction
was observed by using 2 M equivalents of the RLi; 6 M equivalents were
required to engage completely the substrate. Variable amounts of hydra-
zone were recovered when intermediate quantities were used (no explana-
tion was given).[24] One of the first studies of reactions of organolithiums
with nitrosamines reported variable products depending on the substitu-
ents in the nitrosamine and the nature of the organolithium; in most cases
the yields were around 30% or less.[29] It was suggested that azomethine
intermediates are formed and subsequently dimerize head to tail to form
the isolated sym-hexahydrotetrazines. The authors’ attempts to synthe-
size hydrazones were unsuccessful, and only in one case could a trialkyl-
hydrazine be obtained. When N-methyl-tert-butylnitrosamine was treated
with tert-butyllithium and quenched with ethanol, 1,2-tert-butyl-1-
(ethoxymethyl)hydrazine was formed.[29] Nevertheless, under the condi-
tions of the present study, hydrazones could be isolated in good yields.
Azomethines could be suggested as likely intermediates in a complex
reaction scheme as outlined here, which is consistent with the observed
results for the formation of products 2, 3, and 6. Reactions of nitrosamines
with Grignard reagents were previously studied, but the yields were not
good.[30] In some cases, complex mixtures (as least eight products) or tar
products were obtained, even when the reactions were carried out at low
temperatures. Better results were obtained with organolithiums, but only

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´
A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
3964
Scheme 1. Overall mechanistic scheme for the reaction of 1 with n-BuLi.
in one case was a good yield (80%) of the corresponding hydrazone
obtained.[28] Hydrazones can be converted into hydrazides by a one-pot
reduction, followed by an in situ reaction with a carboxylic acid.[31]
The first step in Scheme 1 involves attack by the organolithium
reagent on the nitroso moiety to give adduct 8, which, by elimination of
the elements of HOꢁ Liþ, produces the hydrazone 2c. In smaller amounts,
8 could undergo elimination involving the proton of the a-carbon, produ-
cing the azomethine 10 (presumably through a diazenium salt 9), which
would form the hydrazine 6 (which was isolated in small amounts). By
addition of a second molecule of RLi to the C ¼ N bond, the adduct 12
was formed, which after quenching produces the trialkylhydrazines 3.
Lateral products 4 and 5 can be explained by a denitrosation process,
likely occurring through a nitrosiminium ion intermediate stabilized by
resonance. Rajama¨ki and coworkers[32] reported the first evidence of
the intermediacy of N-nitrosiminium ions in the nonenzymatic decompo-
sition of some a-acetoxy-N-nitrosodialkylamines. Denitrosation of the
N-nitrosiminium intermediate and simultaneous reduction could be the
route for formation of side products 4 and 5.
CONCLUSIONS
The reaction of dialkylnitrosamines with organolithium reagents provide
a simple route for the synthesis of substituted hydrazones, and especially

Convenient Synthesis of Trialkylhydrazines
3965
for the synthesis of multisubstituted hydrazines, which have acquired
renewed interest for their wide versatile properties. Trialkyl hydrazines
can be formed by a one-pot, one-step reaction using excess of the orga-
nolithium reagent; this method circumvents side reactions and avoids
lengthy purification of products, problems sometimes associated with
older synthetic methods. Several suitable groups can be introduced by
selecting a different RLi, for a further reaction of the initially formed
aldehyde hydrazones. This procedure avoids the extra steps required
by previous methods that use protecting groups and the selective cleav-
age of those for the synthesis of multisubstituted hydrazines. Lateral
products isolated in small amounts suggest some likely mechanistic
routes.
EXPERIMENTAL
Warning: Most N-nitrosamines are powerful, direct-acting carcinogens;
they have to be handled and disposed of with special care to avoid skin
contact. Manipulations were carried out using frequently changed double
pairs of disposable gloves in a well-ventilated hood. Contaminated mate-
rials were disposed of in special containers for further disposition of the
still potentially contaminated materials.
General Remarks
All reactions involving organolithium reagents were carried out by
standard techniques for the manipulation of air- and water-sensitive
compounds, as previously described.[33] The product identification was
carried out by melting point (when available) and spectroscopic data.
Product quantification was carried out using a 5890 Series II Plus
Hewlett-Packard gas chromatograph (equipped with a DB-5 column), at
70–280ꢀC programmed temperature. Mass spectra (MS) were recorded
1
on a BG Trio-2 spectrometer. H and 13C NMR spectra were recorded
in Brucker 200-MHz and Brucker 500-MHz NMR spectrometers.
Solvents and Reagents
Hexane and THF (high-performance liquid-chromatographic grade)
were distilled from blue solutions of sodium–benzophenone ketyl imme-
diately before use. n-Butyllithium (1 M in n-hexane solution) was synthe-
sized as previously described, starting from n-butyl-chloride.[20] n-PrLi

ꢀ
´
A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
3966
and n-pentyl Li (0.5 M hexane solutions) were prepared similarly to
n-BuLi, starting from the respective alkylbromides. Solid MeLi was pre-
pared from metal–halogen exchange, starting from n-BuLi (5 mmol) and
with the addition of 0.62 ml of MeI (5 mmol) in several aliquots at 0ꢀC.
The precipitated MeLi was centrifuged, the solution was removed, and
the white crystals were washed three times with 3 ml of anhydrous hexane
followed by centrifugation each time. The resulting solid was dried under
vacuum at room temperature and dissolved in THF immediately before
use. Solid PhLi was prepared from metal–halogen exchange by the same
procedure described for MeLi, with 1.2 ml of PhI (5.25 mmol) replacing
the MeI. All organolithium reagents were titrated with the double titra-
tion method, previously described.[33] N-Nitrosodicyclohexylamine, 1,
was synthesized by NO insertion into the N-Li bond of dicyclohexyl
lithium amide following the procedure previously described.[34] It was
purified by crystallization from ethanol–water and washed with cold
absolute ethanol (mp 104–105ꢀC).[16] The compound was kept in a desic-
cator overnight prior to use.
Synthesis of Hydrazines 3 and 7
N-Nitrosodicyclohexylamine, 1 (210 mg, 1 mmol), was put in a 10-ml
round–bottomed flask equipped with a magnetic stirrer and protected
from light by aluminum paper. The flask was tapped with a rubber septum;
it was placed in a bath at the desired temperature and then alternately
evacuated and filled with dry N2 several times. Two ml of anhydrous
THF were added to dissolve the nitrosamine. Then, the organolithium
solution (4–5 mmol in n-hexane) was added by syringe under vigorous
stirring and allowed to react for 2 h at room temperature. When two dif-
ferent organolithiums are used, the first one was added in a small excess
(1.05–1.2 mmol), and the second (3–5 equivalents) was added later (after
5 min). It was allowed to react for 2 h. Workup was carried out by placing
the flask in a water–ice bath, and distilled methanol (ca. 0.65 ml) was
syringed. The solvent of the resulting mixture was distilled at reduced
pressure, and the liquid residue was purified by silica-gel column chroma-
tography (when necessary), obtaining the hydrazines as air-sensitive pale
yellow oils, or dissolved in CH2Cl2 prior to GC analysis.
Spectroscopical Data
All the compounds herewith described were fully characterized by 1H and
13C NMR and mass spectroscopy.

Convenient Synthesis of Trialkylhydrazines
3967
N-Nitrosodicyclohexylamine, 1
1H NMR (CDCl3, 200 MHz): 4.88 (m, 1H), 3.72 (m, 1H), 1.16–1.96
(m, 20H). 13C NMR (CDCl3, 50 MHz): 58.6, 52.2, 34.4, 29.4, 26.1,
25.5, 25.4, 25.3. MS m=z (rel. ab.): 41 (41), 44 (13), 54 (13), 55 (100),
56 (16), 67 (20), 81 (13), 82 (15), 83 (90), 98 (17), 129 (22), 210 (20, Mþ).
2,2-Dicyclohexyl-1-methylenehydrazine, 2a
1H NMR (CDCl3, 200 MHz): 6.01 (dd, 2H), 3.29 (tt, 2H), 1.76 (m, 12H),
1.35 (m, 8H). 13C NMR (CDCl3, 50 MHz): 114.4, 55.5, 31.3, 26.2, 25.9.
MS: m=z (rel. int.): 40 (78), 41 (54), 43 (15), 44 (10), 55 (75), 56 (16),
69 (44), 70 (16), 83 (100), 84 (10), 125 (14), 165 (27), 208 (19, Mþ).
2,2-Dicyclohexyl-1-propylidenehydrazine, 2b
1H NMR (CDCl3, 200 MHz): 6.83 (t, 1H), 3.13 (tt, 2H), 2.24 (m, 2H),
1.74 (m, 13H), 1.29 (m, 4H.), 1.06 (t, 3H), 0.87 (m, 3H.). 13C NMR
(CDCl3, 50 MHz): 139.9, 56.7, 31.1, 26.5, 26.2, 26.1, 11.9. MS m=z (rel.
int.): 54 (13), 55 (100), 56 (32), 58 (18), 67 (10), 69 (27), 81 (10), 82
(13), 83 (44), 96 (16), 97 (13), 98 (22), 111 (72), 125 (88), 153 (11), 155
(17), 193 (48), 207 (65), 236 (39, Mþ).
2,2-Dicyclohexyl-1-butylidenehydrazine, 2c
1H NMR (CDCl3, 200 MHz): 6.86 (t, 1H), 3.12 (m, 1H), 2.23 (m, 1H),
1.89–1.07 (m, 24H), 0.94 (t, 3H). 13C NMR (CDCl3, 50 MHz): 139.9,
56.8, 35.2, 31.0, 26.2, 26.1, 20.9, 13.9. MS m=z (rel. int.): 54 (25), 55
(97), 56 (65), 57 (30), 67 (24), 68 (17), 69 (39), 70 (21), 81 (19), 82 (31),
83 (44), 84 (23), 96 (20), 97 (17), 98 (33), 110 (17), 125 (100), 136 (16),
138 (38), 207 (77), 250 (30, Mþ).
2,2-Dicyclohexyl-1-pentylidenehydrazine, 2d
1H NMR (CDCl3, 200 MHz): 6.84 (t, 1H), 3.11 (m, 1H), 2.22 (m, 1H),
1.75–1.29 (m, 24H), 0.92 (t, 3H). 13C NMR (CDCl3, 50 MHz): 140.4,
56.8, 32.9, 31.0, 29.8, 26.2, 26.1, 22.4, 14.0. MS m=z (rel. int.): 41 (74),
43 (26), 44 (21), 55 (100), 56 (25), 69 (20), 83 (30), 125 (53), 139 (29),
207 (25), 264 (8, Mþ).

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A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
3968
Dicyclohexylethylhydrazone
MS m=z (int. rel.): 54 (12), 55 (100), 56 (21), 69 (27), 82 (13), 83 (60), 84
(23), 96 (10), 97 (99), 98 (16), 124 (11), 125 (40), 139 (17), 179 (67), 180
(13), 207 (17), 222 (41, Mþ).
N,N-Dicyclohexyl-N’-(1-ethylbutyl)hydrazine, 3b
1H NMR (CDCl3, 200 MHz): 2.56 (m, 2H), 1.75 (m, 5H), 1.59 (m, 1H),
1.29 (m, 17H), 0.85 (m, 11H). 13C NMR (CDCl3, 50 MHz): 60.7, 58.9,
34.5, 31.2, 31.0, 26.4, 25.2, 19.0, 14.6, 14.2. MS m=z (rel. int.): 55 (32),
83 (24), 96 (20), 113 (79), 195 (100), 196 (15), 197 (28), 280 (19, Mþ).
N,N-Dicyclohexyl-N’-(1-propylpentyl)hydrazine, 3c
1H NMR (CDCl3, 500 MHz): 2.66 (m, 1H), 2.56 (m, 1H), 1.87 (m, 1H), 1.76
(m, 6H), 1.60 (m, 4H), 1.30 (m, 17H), 1.09 (m, 2H), 0.92 (m, 8H). 13C NMR
(CDCl3, 50 MHz): 60.7, 57.6, 35.1, 32.5, 31.1, 29.9, 28.0, 26.4, 26.2, 23.2,
19.0, 14.6, 14.2. MS m=z (rel. int.): 55 (38), 56 (10), 57 (12), 69 (11), 83
(23), 96 (20), 98 (10), 113 (83), 195 (100), 196 (18), 225 (22), 308 (20, Mþ).
N,N-Dicyclohexyl-N’-(1-butylhexyl)hydrazine, 3d
1H NMR (CDCl3, 500 MHz): 2.66 (m, 1H), 2.57 (tt, 1H), 1.77 (m, 3H),
1.62 (d, 1H), 1.29 (m, 27H), 1.13 (m, 1H), 0.91 (m, 10H). 13C NMR
(CDCl3, 50 MHz): 60.7, 57.8, 32.5, 31.9, 31.1, 29.7, 29.4, 28.0, 26.4,
26.4, 25.4, 23.2, 22.7, 14.2, 14.1. MS m=z (rel. int): 41 (68), 42 (16), 43
(60), 44 (40), 55 (100), 56 (22), 57 (30), 69 (19), 71 (11), 79 (12), 81
(11), 83 (37), 96 (29), 98 (16), 113 (88), 195 (79), 196 (11), 336 (8, Mþ).
Dicyclohexylamine, 4
1H NMR (CDCl3, 200 MHz): 2.60 (m, 2H), 1.73 (m, 10H), 1.17 (m, 10H),
0.80 (s, 1H, interchange with D2O). 13C NMR (CDCl3, 50 MHz): 53.0,
34.4, 26.2, 25.3. MS m=z (rel. int.): 55 (19), 56 (53), 82 (11), 100 (7),
138 (100), 139 (11), 181 (12, Mþ).
N-Ciclohexylidenecyclohexylamine, 5
MS m=z (rel. int.): 53 (12), 54 (32), 55 (68), 56 (18), 57 (14), 67 (24), 68
(12), 69 (35), 70 (11), 79 (10), 80 (13), 81 (24), 82 (21), 83 (30), 91 (14),

Convenient Synthesis of Trialkylhydrazines
3969
96 (21), 97 (11), 98 (100), 124 (12), 136 (57), 150 (15), 178 (10), 179
(32, Mþ).
N,N-Dicyclohexyl-N’-pentylhydrazine, 7a
1H NMR (CDCl3, 200 MHz): 2.64 (m, 1H), 2.55 (m, 1H), 1.84 (m, 1H),
1.68 (m, 6H), 1.61 (d, 1H), 1.33 (m, 19H), 1.15 (m, 2H), 0.91 (t, 3H). 13
C
NMR (CDCl3, 50 MHz): 60.3, 57.1, 32.1, 31.7, 26.9, 26.4, 20.9, 18.3, 13.8.
MS m=z (rel. int): 41 (79), 42 (18), 43 (38), 44 (21), 45 (17), 54 (12), 55
(100), 56 (19), 69 (21), 71 (13), 79 (10), 81 (10), 83 (33), 86 (10), 88
(24), 96 (34), 98 (26), 101 (12), 113 (39), 127 (16), 183 (56), 195 (31),
266 (14, Mþ).
N,N-Dicyclohexyl-N’-(1-ethylpentyl)hydrazine, 7b
1H NMR (CDCl3, 200 MHz): 2.64 (m, 1H), 2.57 (m, 1H), 1.81 (m, 1H),
1.75 (m, 6H), 1.60 (m, 2H), 1.32 (m, 17H), 1.12 (m, 2H), 0.90 (m, 8H). 13
C
NMR (CDCl3, 50 MHz): 61.5, 57.4, 32.4, 29.8, 29.7, 27.8, 26.5, 26.5, 24.2,
19.2, 13.9. MS m=z (int. rel.): 55 (54), 56 (12), 57 (17), 69 (11), 83 (29),
96 (24), 98 (12), 113 (100), 114 (11), 195 (97), 196 (14), 211 (24), 294
(15, Mþ).
N,N-Dicyclohexyl-N’-(1-ethylhexyl)hydrazine, 7c
1H NMR (CDCl3, 200 MHz): 2.63 (m, 1H), 2.56 (m, 1H), 1.86 (m, 1H),
1.74 (m, 6H), 1.62 (m, 2H), 1.33 (m, 19H), 1.11 (m, 2H), 0.92 (m, 8H).
13C NMR (CDCl3, 200 MHz): 60.6, 57.1, 34.8, 32.0, 30.9, 29.8, 29.7,
26.5, 23.8, 17.3, 14.6, 14.1. MS m=z (rel. int.): 41 (58), 42 (11), 43
(35), 44 (17), 55 (85), 56 (22), 57 (20), 69 (17), 71 (11), 79 (11), 83
(37), 96 (33), 98 (18), 113 (100), 195 (94), 196 (13), 225 (17), 308
(10, Mþ).
N,N-Dicyclohexyl-N’-(1-propylbutyl)hydrazine, 7d
1H NMR (CDCl3, 200 MHz): 2.63 (m, 1H), 2.55 (m, 1H), 1.84 (m, 1H),
1.72 (m, 6H), 1.61 (m, 2H), 1.30 (m, 17H), 1.13 (m, 2H), 0.91 (m, 8H). 13
C
NMR (CDCl3, 50 MHz): 61.3, 57.6, 32.3, 28.7, 26.4, 23.1, 19.8, 13.9. MS
m=z (rel. int.): 55 (34), 57 (11), 83 (20), 96 (17), 113 (72), 195 (100), 196
(14), 211 (19), 294 (18, Mþ).

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A. J. Vazquez, C. Rodrıguez, and N. S. Nudelman
3970
N,N-Dicyclohexyl-N’-(1-propylhexyl)hydrazine, 7f
1H NMR (CDCl3, 500 MHz): 2.65 (m, 1H), 2.57 (tt, 1H), 1.77 (m, 3H),
1.61 (d, 1H), 1.30 (m, 25H), 1.12 (m, 1H), 0.91 (m, 10H). 13C NMR
(CDCl3, 125 MHz): 60.6, 57.4, 32.0, 29.6, 29.3, 26.4, 26.4, 25.3, 22.6,
22.6, 18.9, 14.6, 14.0. MS m=z (rel. int.): 41 (32), 43 (23), 55 (68), 56
(14), 57 (16), 69 (18), 71 (11), 83 (31), 96 (22), 98 (14), 113 (95), 195
(100), 196 (15), 239 (11), 322 (6, Mþ).
N,N-Dicyclohexyl-N’-(1-butylpentyl)hydrazine, 7g
1H NMR (CDCl3, 500 MHz): 2.65 (m, 1H), 2.56 (tt, 1H), 1.87 (m, 1H),
1.76 (m, 6H), 1.61 (m, 2H), 1.43 (m, 2H), 1.28 (m, 19H), 1.11 (m, 2H),
0.92 (m, 8H). 13C NMR (CDCl3, 125 MHz): 60.8, 57.8, 32.6, 28.1, 26.4,
26.3, 23.2, 22.6, 14.2. MS m=z (rel. int.): 41 (30), 43 (20), 55 (62), 56
(15), 57 (17), 69 (17), 71 (10), 83 (28), 96 (22), 98 (12), 113 (96), 195
(100), 196 (14), 239 (11), 322 (6, Mþ)
ACKNOWLEDGMENTS
A.V. and C.R. are grateful recipients of the National Research Council
(CONICET) fellowships. The authors are indebted to the United Nations
Environmental Program (Project PNUD=ARG 02=18 Subproj. B-C-53)
and to CONICET (PIP no. 6019) for financial support.
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