Organic Process Research & Development
Article
some advantages as catalyst support. They are relatively
inexpensive, possess a high surface area, allow easy recovery
of supported metal by simple combustion of the support, show
chemical inertness both in acidic and basic media, and at the
same time do not contain very strongly acidic centers on their
surface, which could provoke undesirable side reaction during
the catalytic run.10 Up to 75% of hydrogenolysis reactions are
currently carried out over Pd/C catalysts.11 Most of the
investigations for TADB (2) production from HBIW (1) were
carried out by palladium catalyst on activated carbon.12,13 Some
attempts were made to optimize the requirement of the Pd
catalyst as an economy measure.14−16
Micromeritics ASAP 2010 instrument. Catalyst sample had
been degassed under vacuum for 3 h at 150 °C prior to
measurement. The specific surface and pore size distribution
were calculated using both Brunauer, Emmett, and Teller
(BET) and Barrett−Joyner−Halenda (BJH) models, respec-
tively. Chemical adsorption (chemisorption) analyses can
provide much of the information needed to evaluate catalyst
materials. So, the hydrogen adsorption isotherm was used to
measure the active surface of the catalyst and also the
distribution of the palladium on the surface of the catalyst. In
this regard, catalyst samples were held under vacuum at 400 °C.
Then, the temperature was decreased to 30 °C and hydrogen
pressure was increased for recording the isotherm.
Response surface methodology (RSM), a branch of
experimental design methodology, introduced by Box and
Wilson,17 is useful for the evaluation of the effects of multiple
factors and their interactions and can be effectively used to find
the combinations of these factors, which will produce an
optimal response. It is advantageous compared with univariate
optimization because it allows the achievement of optimum
conditions with a few experiments and permits the observation
of the interactions between variables, which is not possible
when univariate approaches are used. Central composite design
(CCD), a second-order technique of RSM, makes it easy to
arrange and interpret experiments in comparison with others,
and is widely applied in many studies. Over the past decades,
some researchers have applied experimental design method-
ology for controlling different factors affecting heterogeneous
catalytic reactions. Cukic et al. applied D-optimal design as a
well-known design of experiment (DoE) approach for
evaluating the influence of preparation variables on the
performance of the Pd/Al2O3 catalyst in the hydrogenation of
1,3-butadiene.18 A fractional factorial design as another DoE
approach was applied to investigate the influence of seven
preparation factors on the hydrogenolysis of aryl halides by pd/
C catalysis.19 Blondet et al. employed an experimental design
methodology to optimize the hydrogenation of nitrotoluene
using Pd supported on chitosan hollow fibers.20
Scanning electron microscopy (SEM) and transmission
electron microscopy (TEM) were utilized to evaluate the
surface topology of the catalyst. SEM and TEM images (see
Figure 5) were obtained by Hitachi S4160 and Philips S4160
instruments, respectively.
Finally, the loading percent of palladium on the catalyst was
measured by inductively coupled plasma (ICP) analysis.
2.3. Reductive Debenzylation of HBIW. The catalytic
debenzylation of HBIW (1) was carried out in a 2 L stainless
steel reactor (Buchi bmd 075) equipped with a turbine stirrer
(18.6 rpm), a temperature probe, a heating jacket, and a system
of gaseous hydrogen supply. A schematic representation of the
experimental setup is shown in Figure 1.
The aim of the present investigation was to optimize the
catalytic conversion of HBIW (1) to TADB (2) by employing
response surface methodology. The effects of palladium catalyst
loading, reaction temperature, reaction time, and acetic
anhydride (Ac2O) stoichiometry on the yield of the reaction
were systematically analyzed using CCD.
Figure 1. Schematic representation of experimental set up: (a)
impeller; (b) motor; (c) thermocouple; (d) temperature and agitation
speed control panel; (e) oil circulation; (f) hydrogen cylinder; (g)
nitrogen cylinder; (h) pressure gauge.
2. EXPERIMENTAL SECTION
2.1. Chemicals and Materials. HBIW (1) as a precursor
material for HNIW (4) was synthesized as proposed in ref 21
and primarily washed with ethanol and then recrystallized from
ethyl acetate. Purified HBIW (1) was characterized by
measuring its melting point and TLC. DMF, acetic anhydride,
and bromobenzene were supplied by Merck (Germany) and
were used as a cosolvent, acetylation reagent, and cocatalyst,
respectively. PdCl2 was purchased locally. Activated carbons
and sodium carbonate, which were used as catalyst support and
basic agent, were both Merck grade (see Supporting
Information). Deionized water was also used throughout the
study. Synthesized TADB (2) samples were characterized by
melting point (315−317 °C) and TLC. These two techniques
revealed that the synthesis TADB was pure. In addition, the
FT-IR and 1H NMR spectra of the product completely
complied with published data.22,23
Each experiment was carried out by mixing HBIW (1) (5 g, 7
mmol) in dimethylformamide (DMF; 50 mL, 10 volumes) with
freshly synthesized palladium catalyst (0.25−1 g, 5−20 wt %)
according to the planned experiments. As suggested by Koskin
et al.,24 bromobenzene (0.45 mL, 4.28 mmol), a source of
hydrogen bromide, was added to the reaction mixture as a
cocatalyst. The hydrogenolysis of the C−N bond can be
accelerated in the presence of PhBr. Thereafter, acetic
anhydride (Ac2O; 5−10 mL, 53−106 mmol) as acetylating
agent was added to the mixture. During the reaction, the
hydrogen pressure and reaction temperature were kept between
the values of 2.5−6 bar and 35−55 °C, respectively. The
hydrogenolysis was performed over a 4 h period. At the end of
an experiment, catalyst and the product (TADB (2)) were
filtered off (sinter porosity 4) and were rinsed with acetone.
Precipitated TADB was dissolved in acetic acid, and then the
2.2. Characterization of Catalyst. The nitrogen adsorp-
tion/desorption isotherm was measured at 77 K using a
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dx.doi.org/10.1021/op300162d | Org. Process Res. Dev. 2012, 16, 1733−1738