Synthesis of oleophilic electron-rich phenylhydrazines

Article abstract of DOI:10.3762/bjoc.8.29

Phenylhydrazines 1 substituted with two or three long-chain alkyl, alkoxy or alkylsulfanyl groups were successfully prepared by acid-induced removal of the Boc group in hydrazides 2. The reaction is carried out with 5 equivalents of TfOH in CF₃

Full text of DOI:10.3762/bjoc.8.29

Synthesis of oleophilic electron-rich
phenylhydrazines
Aleksandra Jankowiak1 and Piotr Kaszyński*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 275–282.
1Organic Materials Research Group, Department of Chemistry,
doi:10.3762/bjoc.8.29
Vanderbilt University, Nashville, TN 37235 and 2Faculty of Chemistry,
University of Lódź, Tamka 12, 91403 Lódź, Poland
Received: 14 November 2011
Accepted: 06 February 2012
Published: 20 February 2012
Email:
Piotr Kaszyński* - piotr.kaszynski@vanderbilt.edu
This article is part of the Thematic Series "Progress in liquid crystal
chemistry II".
* Corresponding author
Keywords:
Guest Editor: S. Laschat
arylhydrazines; methodology; synthesis
© 2012 Jankowiak and Kaszyński; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Phenylhydrazines 1 substituted with two or three long-chain alkyl, alkoxy or alkylsulfanyl groups were successfully prepared by
acid-induced removal of the Boc group in hydrazides 2. The reaction is carried out with 5 equivalents of TfOH in CF3CH2OH/
CH2Cl2 at −40 °C for 1.5 min. Under these conditions, the deprotected hydrazine 1 is fully protonated, which increases its stability
in the reaction medium. The hydrazines were isolated in 60–86% yields and purities >90%. The hydrazides 2 were obtained in
43–71% yields from aryl bromides 5, which were lithiated with t-BuLi and subsequently reacted with di-tert-butyl azodicarboxy-
late (DTBAD).
Introduction
Mono-arylhydrazines I are important intermediates in the syn- In contrast, electron-rich arylhydrazines are far less numerous
thesis of a number of heterocycles, including indoles [1] and and their preparation is complicated by oxidative instability.
some azoles (for example [2,3]), many of which exhibit bio-
logical activity and are used in drug development [4-6]. Arylhy- To access functionalized and sensitive arylhydrazines several
drazines are also key intermediates in the preparation of stable methods involving the deprotection of hydrazides II have been
radicals such as verdazyl [7-9] and benzo[1,2,4]triazinyls [10- developed (Figure 1). Hydrazides II are efficiently obtained by
12].
the addition of organometallic reagents III, prepared from aryl
halide IV, to azodicarboxylate diesters (AD) [16,17]. Alter-
The parent phenylhydrazine and many of its electron-deficient natively, II can be obtained in the Pd(0)- or Cu2+-catalyzed
derivatives, such as p-nitrophenylhydrazine, are stable under reaction of arylboronic acid V to AD [18-20]. The latter method
ambient conditions and are conveniently obtained by using clas- is especially suited for arylhydrazides substituted with sensitive
sical methods, such as the reduction of diazonium salts [13-15]. functional groups. Protected electron-rich arylhydrazines,
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Beilstein J. Org. Chem. 2012, 8, 275–282.
Figure 1: Selected methods for the preparation of arylhydrazines I through hydrazides II.
hydrazides II, containing the 2,2,2-trichloroethyl group (R = (Figure 2) substituted with multiple long-chain alkyl, alkoxy
CH2CCl3) are conveniently prepared by direct electrophilic and alkylsulfanyl groups. Here we demonstrate an efficient
amination of arenes VI with bis(2,2,2-trichloroethyl) azodicar- method for the preparation of several hydrophobic di- and tri-
boxylate (BTCEAD) under Lewis [21,22] or Brønsted [23] acid substituted phenylhydrazines in purities sufficient for further
conditions.
chemical transformations. Finally, we demonstrate the applica-
tion of one of the phenylhydrazines for the preparation of a
By judicious choice of the substituent R, the removal of the discotic liquid crystal.
protecting group in II and formation of arylhydrazines I can be
accomplished under acidic (R = t-Bu) [16], reductive (R = Results and Discussion
CH2CCl3) [24], or nearly neutral (R = CH2CH2TMS) condi- Our initial attempts at the preparation of 3,4-dioctyloxyphenyl-
tions [22,25]. Among the three methods, the most straightfor- hydrazine (1a) focused on deprotection of the trichloroethyl
ward is the removal of the Boc group under acidic conditions. ester 3a under buffered reductive conditions, according to the
Unfortunately, the literature method for deprotection (HCl in general literature procedure [24]. In aqueous MeOH hydrazide
isopropanol, 70 °C) has limited scope, and electron-rich 3,4- 3a was practically insoluble, and the reaction mixture was
dimethoxyphenylhydrazine could not be obtained under these triphasic. Under these conditions no formation of hydrazine 1a
conditions, although 4-pentyloxyphenylhydrazine hydrochlo- was observed. Changing MeOH to EtOH and increasing its
ride was isolated in 60% yield [16]. The controlled reduction of volume by two-fold gave homogenous solutions within which
2,2,2-trichloroethyl esters (II, R = CH2CCl3) with Zn in the desired hydrazine 1a was formed along with significant
aqueous MeOH containing NH4OAc gave access to a number quantities of 4 as the major products (Scheme 1). The deamina-
of small, electron-rich phenylhydrazines, including 3,4- tion product 4 was isolated and identified by comparison with
dimethoxyphenylhydrazine isolated in 76% yield as hydrochlo- the authentic sample. The yield and proportions of the two
ride [24].
products, 1a and 4, varied from run to run, according to the
1H NMR spectra. Therefore, we focused on the acid-catalyzed
In the context of our research program in liquid-crystalline deprotection of Boc-substituted hydrazines (Scheme 2),
verdazyl derivatives [26], we needed phenylhydrazines 1 hydrazides 2, expecting that the reaction could be performed
under fully homogenous conditions.
Analysis of the reaction mechanism for the deprotection of 2
under acidic conditions shows that removal of the Boc group
generates t-Bu+, which reacts with the solvent, or alternatively
it can alkylate the benzene ring of arylhydrazine (Scheme 2).
For less reactive arylhydrazines the former process is faster,
k1 << k2, and deprotection with HCl in iPrOH is effective [16].
For dialkoxyphenylhydrazines apparently k1 >> k2 and the
Figure 2: The structures for hydrazines 1a–1h.
desired hydrazine is not obtained [16].
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Beilstein J. Org. Chem. 2012, 8, 275–282.
Scheme 1: Formation and deprotection of 3a under reductive conditions.
partially converted to hydrazine 1a. With 5 equiv of TfOH the
reaction was complete in less than 2 min and the crude
hydrazine 1a was isolated as the sole product. Reaction times
under 2 min appear to be optimum; the purity of the hydrazine
decreased with increasing reaction times.
By using this protocol, hydrazines 1 were isolated as viscous
oils in purities >90% and yields of 60–86%, according to
1H NMR analysis with 1,4-dimethoxybenzene as the internal
standard (Scheme 3). Attempts at the preparation of crystalline
hydrochlorides of 1 were unsuccessful and the viscous salts
rapidly darkened and decomposed.
Scheme 2: General mechanism for the deprotection of arylhydrazides.
G represents a substituent.
The nucleophilicity of the hydrazine can be suppressed by its
fast and complete protonation with a strong acid (Scheme 2). In
this situation, the transient t-Bu+ is trapped with the solvent,
forming volatile products, which simplifies isolation of the
hydrazine as a crude product. We have focused on this ap-
proach to arylhydrazines employing trifluoromethanesulfonic
acid (TfOH), which was used as an effective catalyst in the
deprotection of tert-butyl aryl ethers [27].
Addition of catalytic amounts of the TfOH acid (10 mol %) to
solutions of hydrazide 2a (Figure 3) in a mixture of
CF3CH2OH/CH2Cl2 at −40 °C gave little conversion to
hydrazine 1a. With 1.5 equiv of TfOH, hydrazide 2a was only
Scheme 3: Synthesis of arylhydrazines 1. Substituents X and Y are
defined in Figure 2.
The Boc-protected arylhydrazines, hydrazides 2, were conve-
niently obtained by direct addition of aryllithium to di-tert-butyl
azodicarboxylate (DTBAD, Scheme 3). The latter was prepared
by lithiation of aryl bromides 5 with t-BuLi to avoid the forma-
tion of n-BuBr with n-BuLi and N-butylation of hydrazide 2.
Hydrazide 2a was also obtained by the Cu2+-catalyzed addition
[18] of arylboronic acid 6a [28] to DTBAD. The yields of both
syntheses of 2a were comparable.
Figure 3: Structure of hydrazide 2a.
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Beilstein J. Org. Chem. 2012, 8, 275–282.
The trichloroethyl hydrazide 3a was prepared by acid-catalyzed
amination of 1,2-dioctyloxybenzene (4) with BTCEAD in the
presence of catalytic amounts of TfOH, according to a general
literature procedure [23] (Scheme 1).
The requisite bromobenzene 5a was prepared by bromination of
1,2-dioctyloxybenzene (4) [29] with CuBr2 in MeCN according
to a literature method [30] (Scheme 4). This method is a con-
venient alternative to the alkylation of the less readily acces-
sible 4-bromocatechol (7) [28].
Scheme 5: Preparation of 5b.
The preparation of bromobenzenes substituted with alkylsul-
fanyl groups, 5c–5f, is described elsewhere [38]. Bromides 5g
[39,40] and 5h [41] were obtained according to the respective
literature procedures by alkylation of 5-bromopyrogallol.
The 3,4,5-trialkylsulfanylphenylhydrazines 1c–1f have been
used in the preparation of 6-oxoverdazyl derivatives that ex-
hibit liquid-crystalline properties [26]. For instance, radical 9,
prepared from 1d (Figure 4), exhibits a monotropic columnar
rectangular phase (Cr 62 (Colr 60) I), a broad absorption band
in the visible region, and redox potentials E0/+11/2 = +0.99 V
and E0/−11/2 = −0.45 V versus SCE. Photovoltaic studies of 9
demonstrated hole mobility μh = 1.52 × 10−3 cm2 V−1s−1 in the
mesophase with an activation energy Ea = 0.06 ± 0.01 eV.
Scheme 4: Preparation of bromide 5a.
1-Bromo-3,4-didecylbenzene (5b) was obtained by bro- Conclusion
mination of 1,2-didecylbenzene (8) [31], obtained by the We have developed a synthetic protocol for the efficient prepar-
Kumada method [32], with Br2 in acetic anhydride (Scheme 5). ation of electron-rich phenylhydrazines 1 substituted with alkyl-
Typically, the electrophilic bromination of 1,2-dialkylbenzenes sulfanyl, alkyl and alkoxy groups from Boc hydrazides 2.
results in 4,5-dibromo derivatives as the major products [33,34]. Experiments demonstrate that the addition of hydrazides 2 to a
In contrast, the present method permits selective monobromina- large excess of TfOH (5 equiv) at −40 °C gives hydrazines 1 in
tion, although the bromo derivative 5b was isolated only in yields ranging from 60–86% and with purity >90%, which is
about 85% purity. The product could not be purified rigorously sufficient for subsequent chemical transformations. The
from several unidentified contaminants either by chromatog- optimum reaction time is less than 2 min, typically 90 sec, and
raphy or by distillation due to the lack of separation or partial longer times lead to a lower purity of the product.
decomposition. Therefore, crude 5b was used for the prepar-
ation of hydrazide 2b, which was easily purified by chromato- The presented method for the preparation of phenylhydrazines
graphic methods.
is an attractive alternative to Leblanc’s method, which relies on
the reductive deprotection of trichloroethyl hydrazide 3 under
The attempted monoiodination of 8 with BTMA·ICl2 by using a heterogenous conditions. Our method involves homogenous
general literature method [35] gave only traces of the product solutions, low temperatures and short reaction times, and is
and nearly all of the starting material was recovered. Iodination particularly suited to oleophilic (“greasy”) arylhydrazines such
under the Kern conditions [36,37] (HIO3/I2) gave a mixture of as 1, which are important intermediates for the preparation of
mono- and diiodo derivatives, which were difficult to separate. verdazyls and other heterocycles that may exhibit, e.g., liquid-
Manipulation of the reaction time and temperature failed to give crystalline properties (e.g., 9). In comparison with Leblanc’s
the desired monoiodo derivative as the major product.
protocol, our method is also a regiocontrolled hydrazinylation
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Beilstein J. Org. Chem. 2012, 8, 275–282.
Figure 4: The structure of verdazyl radical 9 and a texture of the Colr phase.
of the aromatics with the more accessible DTBAD through the 16H), 1.37–1.46 (m, 4H), 1.61 (quint, J = 7.0 Hz, 2H), 1.68
organolithium. Although we focus on long-chain-substituted (quint, J = 6.9 Hz, 2H), 3.78 (t, J = 6.4 Hz, 2H), 3.87 (t, J = 6.3
phenylhydrazines, we believe that this method can be used for Hz, 2H), 6.24 (dd, J1 = 8.5 Hz, J2 = 2.3 Hz, 1H), 6.47 (d, J =
other electron-rich arylhydrazines.
2.3 Hz, 1H), 6.71 (d, J = 8.6 Hz, 1H).
Experimental
3,4-Didecylphenylhydrazine (1b): 1H NMR (500 MHz,
Reagents and solvents were obtained commercially. Reactions CDCl3) δ 0.88 (t, J = 6.9 Hz, 6H), 1.22–1.40 (m, 28H),
were carried out under Ar. 1H NMR spectra were obtained at 1.47–1.58 (m, 4H), 2.51 (t, J = 7.0 Hz, 2H), 2.53 (t, J = 7.1 Hz,
400 MHz in CDCl3 and referenced to the solvent, unless speci- 2H), 2.6 (brs, 3H), 6.59–6.65 (m, 2H), 7.01 (d, J = 8.0 Hz, 1H).
fied otherwise.
3,4,5-Trihexylsulfanylphenylhydrazine (1c): 1H NMR (400
Arylhydrazines 1
General procedure
MHz, CDCl3) δ 0.87 (t, J = 6.9 Hz, 3H), 0.89 (t, J = 6.8 Hz,
6H), 1.20–1.35 (m, 12H), 1.36–1.52 (m, 6H), 1.59 (quint, J =
A solution of hydrazide 2 (1 mmol) in a mixture of CH2Cl2 7.5 Hz, 2H), 1.71 (quint, J = 7.4 Hz, 4H), 2.77 (t, J = 7.4 Hz,
(3 mL)/CF3CH2OH (1 mL) was rapidly added to a solution of 2H), 2.83 (t, J = 7.3 Hz, 4H), 3.2 (brs, 3H), 6.41 (s, 2H).
TfOH (0.750 g, 0.44 mL, 5 mmol) in CF3CH2OH (1 mL) at
−40 °C under Ar. The mixture was stirred for 1.5 min, and 3,4,5-Trioctylsulfanylphenylhydrazine (1d): 1H NMR (500
CH2Cl2 (5 mL) followed by sat. NaHCO3 (10 mL) were added MHz, CDCl3) δ 0.87 (t, J = 6.9 Hz, 3H), 0.88 (t, J = 6.6 Hz,
under very vigorous stirring. The organic layer was separated 6H), 1.20–1.34 (m, 24H), 1.38–1.43 (m, 2H), 1.44–1.53 (m,
and the aqueous layer extracted (3 × CH2Cl2). Then the extracts 4H), 1.59 (quint, J = 7.5 Hz, 2H), 1.72 (quint, J = 7.5 Hz, 4H),
were dried (Na2SO4) and the solvents were evaporated to give 2.77 (t, J = 7.5 Hz, 2H), 2.84 (t, J = 7.4 Hz, 4H), 6.40 (s, 2H).
crude arylhydrazine 1 in purities typically >90% as a viscous,
yellow to orange oil that darkened upon standing. The quantitat- 3,4,5-Tridecylsulfanylphenylhydrazine (1e): 1H NMR (400
ive analysis of the deprotection reaction was conducted with MHz, CDCl3) δ 0.87 (t, J = 6.8 Hz, 3H), 0.88 (t, J = 6.8 Hz,
0.2 mmol of 2 as described above. The yield of the hydrazines 6H), 1.20–1.35 (m, 36H), 1.36–1.52 (m, 6H), 1.59 (quint, J =
was established by adding known quantities of 1,4-dimethoxy- 7.6 Hz, 2H), 1.71 (quint, J = 7.3 Hz, 4H), 2.76 (t, J = 7.5 Hz,
benzene (2.0 mL of 25 mM solution in CH2Cl2, 0.05 mmol) to 2H), 2.83 (t, J = 7.3 Hz, 4H), 6.40 (s, 2H).
the CH2Cl2 extract, evaporation of the resulting solution, and
integration of the low-field 1H NMR signals.
3,4,5-Tridodecylsulfanylphenylhydrazine (1f): 1H NMR (500
MHz, CDCl3) δ 0.88 (t, J = 6.8 Hz, 9H), 1.20–1.35 (m, 48H),
3,4-Dioctyloxyphenylhydrazine (1a): 1H NMR (400 MHz, 1.36–1.51 (m, 6H), 1.59 (quint, J = 7.5 Hz, 2H), 1.71 (quint, J =
CDCl3) δ 0.88 (t, J = 6.8 Hz, 6H), 1.26–1.36 (m, 16H), 7.4 Hz, 4H), 2.77 (t, J = 7.4 Hz, 2H), 2.84 (t, J = 7.1 Hz, 4H),
1.37–1.47 (m, 4H), 1.70–1.85 (m, 4H), 3.92 (t, J = 6.7 Hz, 2H), 6.40 (s, 2H).
3.96 (t, J = 6.7 Hz, 2H), 6.34 (dd, J1 = 8.5 Hz, J2 = 2.6 Hz, 1H),
6.46 (d, J = 2.6 Hz, 1H), 6.82 (d, J = 8.5 Hz, 1H); 1H NMR 3,4,5-Trioctyloxyphenylhydrazine (1g): Soft yellow solid;
(500 MHz, DMSO-d6) δ 0.86 (t, J = 6.7 Hz, 6H), 1.20–1.36 (m, 1H NMR (400 MHz, CDCl3) δ 0.88 (t, J = 6.7 Hz, 9H),
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Beilstein J. Org. Chem. 2012, 8, 275–282.
1.22–1.38 (m, 24H), 1.42–1.53 (m, 6H), 1.72 (quint, J = 7.1 Hz, 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-trihexylsulfanyl-
2H), 1.79 (quint, J = 7.1 Hz, 4H), 3.86 (t, J = 6.6 Hz, 2H), 3.95 phenyl)hydrazine (2c): Yield 43%; mp 74–75 °C; 1H NMR
(t, J = 6.6 Hz, 4H), 6.06 (s, 2H).
(400 MHz, CDCl3) δ 0.87 (t, J = 6.9 Hz, 3H), 0.88 (t, J = 6.9
Hz, 6H), 1.23–1.37 (m, 12H), 1.38–1.52 (m, 6H), 1.51 (s, 18H),
3,4,5-Tridecyloxyphenylhydrazine (1h): 1H NMR (400 MHz, 1.60 (quint, J = 7.4 Hz, 2H), 1.72 (quint, J = 7.2 Hz, 4H), 2.81
CDCl3) δ 0.88 (t, J = 6.8 Hz, 9H), 1.21–1.38 (m, 36H), (t, J = 7.5 Hz, 2H), 2.84 (t, J = 7.4 Hz, 4H), 6.69 (brs, 1H), 6.99
1.39–1.64 (m, 6H), 1.65–1.84 (m, 6H), 3.86 (t, J = 6.6 Hz, 2H), (brs, 2H); Anal. calcd for C34H60N2O4S3: C, 62.15; H, 9.20; N,
3.95 (t, J = 6.6 Hz, 4H), 6.06 (s, 2H); 1H NMR (400 MHz, 4.26; found: C, 62.35; H, 9.34; N, 4.22.
C6D6) δ 0.92 (t, J = 6.8 Hz, 9H), 1.22–1.58 (m, 38H), 1.63–1.73
(m, 4H), 1.78 (quint, J = 7.1 Hz, 4H), 1.97 (quint, J = 8.3 Hz, 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-trioctylsulfanyl-
2H), 3.89 (t, J = 6.4 Hz, 4H), 4.23 (t, J = 6.5 Hz, 2H), 6.03 (s, phenyl)hydrazine (2d): Yield 55% yield; mp 51–52 oC;
2H).
1H NMR (400 MHz, CDCl3) δ 0.84–0.91 (m, 9H), 1.21–1.35
(m, 24H), 1.36–1.50 (m, 6H), 1.51 (s, 18H), 1.60 (quint, J = 7.4
Hz, 2H), 1.72 (quint, J = 7.5 Hz, 4H), 2.81 (t, J = 7.5 Hz, 4H),
2.83 (t, J = 7.4 Hz, 2H), 6.69 (brs, 1H), 6.98 (brs, 2H); the
Preparation of hydrazides 2
General procedure
To a solution of the substituted bromobenzene 5 (1.0 mmol) in analytically pure sample was obtained by recrystallization
dry THF (10 mL), t-BuLi (1.7 M in pentane, 2.2 mmol) was (MeCN); Anal. calcd for C40H72N2O4S3: C, 64.82; H, 9.79; N,
added under Ar at −78 °C. After 1.5 h a THF (1 mL) solution of 3.78; found: C, 64.92; H, 9.56; N, 3.91.
di-tert-butyl azodicarboxylate (DTBAD, 345 mg, 1.5 mmol)
was added dropwise. The mixture was stirred at −78 °C for 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-tridecylsulfanyl-
0.5 h, then 1 h at rt, and quenched with 5% HCl. The organic phenyl)hydrazine (2e): Yield 56%; mp 50–51 °C; 1H NMR
products were extracted (Et2O), the extracts dried (Na2SO4), the (500 MHz, CDCl3) δ 0.87 (t, J = 6.8 Hz, 3H), 0.88 (t, J = 7.0
solvents evaporated, and the residue was passed through a short Hz, 6H), 1.21–1.36 (m, 38H), 1.37–1.51 (m, 6H), 1.51 (s, 18H),
silica-gel column (hexane/CH2Cl2 then CH2Cl2) to give 1.60 (quint, J = 7.4 Hz, 2H), 1.71 (quint, J = 7.4 Hz, 4H), 2.81
hydrazides 2 as white solids.
(t, J = 7.6 Hz, 2H), 2.83 (t, J = 7.4 Hz, 4H), 6.70 (brs, 1H), 6.98
(brs, 2H); Anal. calcd for C46H86N2O4S3: C, 66.78; H, 10.48;
1,2-Bis(tert-butoxycarbonyl)-1-(3,4-dioctyloxyphenyl)- N, 3.39; found: C, 66.75; H, 10.07; N, 3.43.
hydrazine (2a): Yield 71%; mp 55–57 °C; 1H NMR (500 MHz,
CDCl3) δ 0.88 (t, J = 6.9 Hz, 6H), 1.22–1.38 (m, 16H), 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-tridodecylsulfanyl-
1.39–1.51 (m, 4H), 1.49 (s, 18H), 1.73–1.84 (m, 4H), 3.96 (t, J phenyl)hydrazine (2f): Yield 50%; mp 49–51 °C; 1H NMR
= 6.6 Hz, 2H), 3.97 (t, J = 6.6 Hz, 2H), 6.71 (brs, 1H), 6.80 (d, J (500 MHz, CDCl3) δ 0.88 (t, J = 6.7 Hz, 9H), 1.22–1.36 (m,
= 8.6 Hz, 1H), 6.86–6.92 (m, 1H), 6.93–7.02 (m, 1H); Anal. 50H), 1.35–1.51 (m, 6H), 1.51 (s, 18H), 1.60 (quint, J = 7.4 Hz,
calcd for C32H56N2O6: C, 68.05; H, 9.99; N, 4.96; found: C, 2H), 1.71 (quint, J = 7.2 Hz, 4H), 2.81 (t, J = 7.4 Hz, 2H), 2.83
68.35; H, 9.82; N, 5.02.
(t, J = 7.2 Hz, 4H), 6.69 (brs, 1H), 6.98 (brs, 2H); Anal. calcd
for C52H98N2O4S3: C, 68.52; H, 10.84; N, 3.07; found: C,
Method B: To a solution of 3,4-dioctyloxyphenylboronic acid 68.82; H, 10.83; N, 3.06.
(6a, 50 mg, 0.13 mmol) in THF (2 mL), di-tert-butyl
azodicarboxylate (DTBAD, 30 mg, 0.13 mmol) was added 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-trioctyloxy-
followed by Cu(OAc)2 (cat) under an Ar atmosphere. The phenyl)hydrazine (2g): Yield 45%; white crystals (MeCN/
mixture was stirred at rt overnight, the solvent was EtOAc); mp 73–74 °C; 1H NMR (400 MHz, CDCl3) δ 0.88 (t, J
evaporated and the residue was purified on a short = 6.8 Hz, 9H), 1.23–1.38 (m, 24H), 1.38–1.52 (m, 6H), 1.50 (s,
silica-gel column (CH2Cl2) to give 50 mg (68% of yield) of 18H), 1.73 (quint, J = 7.4 Hz, 2H), 1.77 (quint, J = 6.9 Hz, 4H),
hydrazide 2a.
3.92 (t, J = 6.8 Hz, 2H), 3.93 (t, J = 6.6 Hz, 4H), 6.64 (brs, 2H),
6.68 (brs, 1H); Anal. calcd for C40H72N2O7: C, 69.32; H,
1,2-Bis(tert-butoxycarbonyl)-1-(3,4-didecylphenyl)hydrazine 10.47; N, 4.04; found: C, 69.61; H, 10.43; N, 3.91.
(2b): Yield 63%; mp 37–38 °C; 1H NMR (500 MHz, CDCl3) δ
0.88 (t, J = 6.8 Hz, 6H), 1.23–1.40 (m, 28H), 1.49 (s, 18H), 1,2-Bis(tert-butoxycarbonyl)-1-(3,4,5-tridecyloxy-
1.48–1.59 (m, 4H), 2.52–2.59 (m, 4H), 6.70 (brs, 1H), 7.06 (d, J phenyl)hydrazine (2h): Yield 64%; mp 55–57 °C; 1H NMR
= 8.2 Hz, 1H), 7.08–7.21 (br m, 2H); Anal. calcd for (400 MHz, CDCl3) δ 0.88 (t, J = 6.8 Hz, 9H), 1.21–1.38 (m,
C36H64N2O4: C, 73.42; H, 10.95; N, 4.76; found: C, 73.06; H, 38H), 1.41–1.54 (m, 6H), 1.50 (s, 18H), 1.67–1.82 (m, 6H),
10.88; N, 4.74.
3.91 (t, J = 6.8 Hz, 2H), 3.93 (t, J = 6.6 Hz, 4H), 6.64 (brs, 2H),
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Beilstein J. Org. Chem. 2012, 8, 275–282.
6.68 (brs, 1H); Anal. calcd for C46H86N2O7: C, 70.91; H, mmHg) to collect 11.4 g (48% yield) of 1,2-didecylbenzene (8)
11.12; N, 3.60; found: C, 71.31; H, 11.08; N, 3.65.
as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 0.88 (t, J = 6.8
Hz, 6H), 1.20–1.43 (m, 28H), 1.57 (quint, J = 7.7 Hz, 4H), 2.59
1,2-Bis(2,2,2-trichloroethoxycarbonyl)-1-(3,4-dioctyloxy- (t, J = 8.0 Hz, 4H), 7.06–7.16 (m, 4H); HRMS–EI (m/z): [M]+
phenyl)hydrazine (3a): To the solution of 1,2-dioctyloxyben- calcd for C26H46, 358.3600; found, 358.3583.
zene (4, 1.10 g, 3.31 mmol) in dry CH2Cl2 (20 mL), one drop of
CF3SO3H was added under Ar at −78 °C followed by a solu- Acknowledgements
tion of bis(2,2,2-trichloroethyl) azodicarboxylate (BTCEAD, This project was supported by a Vanderbilt University
1.50 g, 3.97 mmol) in CH2Cl2 (3 mL). The reaction mixture Discovery Grant.
was stirred for 20 min, warmed up to rt, stirred for 10 min, and
References
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1.49–1.58 (m, 4H), 2.53 (t, J = 7.4 Hz, 2H), 2.55 (t, J = 7.5 Hz,
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