A Green and Effective Approach of Two-Step 2,2′,4,4′,6,6′-Hexanitrostilbene Preparation and Its Industrial Scale Study

Article abstract of DOI:10.1021/acs.oprd.5b00422

An environmental friendly approach for two-step synthesis of hexanitrostilbene (HNS) has been studied here. In the first step from trinitrotoluene (TNT) to hexanitrobienzyl (HNBB), commercial NaClO was employed as oxidant in mixed solvent of ethyl acetate/ethanol (0.25 mL/1.25 mL per mmol of TNT) instead of benzene/ethanol. In the second step from HNBB to HNS, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)/FeCl₂ was used as an effective catalytic system with O₂ in DMSO solvent. A complex of metal ion and O₂ [M(n+1)OO?] was supposed to be the active agent, and TEMPO itself was difficult to initiate dehydrogenation of HNBB but could promote the catalytic cycle of complex M(n+1)OO?. Finally, we increased the scale from 30 to 1000 g to investigate the feasibility of production. The total yield of two steps would be unprecedentedly as high as 70%.

Full text of DOI:10.1021/acs.oprd.5b00422

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Full Paper
A Green and Effective Approach of Two-step’s 2,2’,4,4’,6,6’-
Hexanitrostilbene Preparation and Its Industrial Scale Study
Peng-cheng Wang, Ting-ting Lu, and Ming Lu
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.5b00422 • Publication Date (Web): 18 Feb 2016
Downloaded from http://pubs.acs.org on February 23, 2016
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A Green and Effective Approach of Twoꢀstep’s
2,2’,4,4’,6,6’ꢀHexanitrostilbene Preparation and
Its Industrial Scale Study
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†
‡
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Pengcheng Wang, *, Ting-ting Lu,†, Ming Lu**,
† School of Chemical Engineering, Nanjing University of Science and Technology,
Nanjing 210094, People’s Republic of China
‡ Xi'an Modern Chemistry Research Institute, Xi'an 710065, People’s Republic of China
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ABSTRACT: An environmental friendly approach for twoꢀstep synthesis of
hexanitrostilbene (HNS) has been studied here. In the first step from trinitrotoluene
(TNT) to hexanitrobienzyl (HNBB), commercial NaClO was employed as oxidant in
mixed solvent of ethyl acetate/ethanol (0.25mL/1.25mL per mmol of TNT) instead of
benzene/ethanol. In the second step from HNBB to HNS, 2,2,6,6ꢀtetramethylpiperidineꢀ
1ꢀoxyl (TEMPO)/FeCl2 was used as an effective catalytic system with O2 in DMSO
solvent. A complex of metal ion and O2 [M(n+1)OOꢁ] was supposed to be the active
agent, and TEMPO itself was difficult to initiate dehydrogenation of HNBB but could
promote the catalytic cycle of complex M(n+1)OOꢁ. Finally, we increased the scale from
30 g to 1000 g to investigate the feasibility of production. The total yield of two steps
would be unprecedentedly as high as 70%.
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KEYWORDS: hexanitrostilbene, oxidation, dehydrogenation, TEMPO/FeCl2, scaleꢀup
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1. Introduction
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2,2’,4,4’,6,6’ꢀHexanitrostilbene (HNS) is an excellent explosive known for its steady
detonation performance under extreme conditions such as high pressure and wide
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o
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temperature range (ꢀ193 C to 280 C).1,2 It has been applied in not only deep petroleum
well perforating, aeronautic and astronautic areas but also heatꢀshock resistance systems
in military ordnance. 3,4
The synthetic route of HNS available for industrial process was firstly disclosed by Shipp
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and Kaplan as shown in Scheme 1. In tetrahydrofuran/methanol mixed solvent, 2,4,6ꢀ
trinitrobenzene was halogenated into trinitrobenzyl chloride (TNBCl), after which
hexanitrobienzyl (HNBB) was generated through coupling followed by the final
formation of HNS through dehydrogenation. Though this was a oneꢀpot reaction, only
35ꢀ40% of yield was obtained. Moreover, the purity was about 90ꢀ95% and
recrystallization was usually required to obtain product of high quality. Several modified
approaches have been found in literatures and the yields were increased to about 50%
with oxidative metal salts as catalysts. Considering that the dehydrogenation of HNBB
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was inefficient in Shipp’s method, Kompothy separated the process into two steps and
HNBB was dehydrogenated under another oxidative condition. In this case, about 60%
and 80% yield could be achieved for HNBB in the first and second step, respectively.
Later, with bromine as the dehydrogenating agent for benzyl, Lu improved the yield of
second step up to 95%.8 The “two steps” method significantly improved the total yield to
55~60% with high purified HNS and thus had been industrialized in China.9 However,
environmental issues relating to dangerous agents Br2 and toxic solvents
benzene/pyridine were also brought about. To solve this problem, an alternative method
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employing NꢀHydroxyphthalimide (NHPI)/FeCl2 as catalyst was investigated in our
recent works to assist the dehydrogenation of HNBB to HNS, which was proved to be a
better choice compared with the previous methods. 10,11
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< Insert Scheme 1 here>
Based on that work, herein we reported a more environmental friendly and industrial
applicable method. Oxygen gas was employed as green oxidant instead of high hazard
bromine in the HNS preparation step with the help of 2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀ
oxyl (TEMPO). Benzene and pyridine solvents of high toxicity were also replaced by
ethyl acetate (EA) and dimethyl sulfoxide (DMSO). This procedure was further enlarged
to middleꢀsize, and several factors in scaleꢀup were investigated with the purpose of
obtaining an industrial available process scheme.
2. Experimental section
Step 1 Synthesis of HNBB: TNT (30/100/1000g) was added into the mixed solvent of
ethyl acetate (0.25mL/mmol of TNT) and ethanol (1.25mL/mmol TNT). The system was
kept in 50 oC for 60 min, followed by the addition of NaClO solution (effective Chlorine
content of 5% and pH value of 13.45, n(NaClO): n(TNT) = 0.53: 1) within 1 min.
Intermediate HNBB was collected by filtration and dried under vacuum.
Step 2 Synthesis of HNS: A 10 L reaction pot containing HNBB (40/100/1000 g),
TEMPO, FeCl2·7H2O of certain amount and DMSO was kept under a constant
temperature of 55 oC under stirring. Oxygen was inputted into the bottom of the solution.
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After 10 h, crude product was obtained through filtration, washed four times with acetone
and dried over 50 oC.
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Step 3 Recycle of catalyst and solvent: (1) The filtrate in step 2 was poured into the
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reaction vessel, followed by the replenish of HNBB and recharge of DMSO, FeCl2·4H2O,
o
TEMPO respectively. The reaction was allowed to proceed at 55 C under stirring.
Oxygen was inputted into the bottom of the solution. After 10 h, crude product was
obtained through filtration, washed fourth with acetone and dried under 50 oC. (2) Repeat
(1) for 3 to 4 times.
3. Results and Discussion
3.1 Preparation of HNBB
3.1.1 Solvent effect
Presently, utilization of NaClO aqueous solution as oxidant was a good choice in the
green preparation process for HNBB. The problem that still existed is to improve the
solubility of TNT in aqueous system, so the option of coꢀsolvent would directly affect the
efficiency of NaClO and yield of oxidation process. Shipp developed a THF/methanol
system with THF as coꢀsolvent. The addition of methanol was to form a better
homogeneous system, as reported by Shipp 6 and Burlinson 12. If water was used together
with THF instead of methanol, however, no products could be obtained. So methanol was
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supposed to participate in the reaction actually. Several solventꢀcoꢀsolvent systems
were tested for the synthesis of HNBB as shown in Figure 1. With dielectric constant
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used as the index of polarity, the relationship between polarity and yields were
demonstrated.
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< Insert Figure 1 here>
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In terms of alcohol solvent, the yield of HNBB increased with the polarity.
Bernasconi14 and Fyfe 15 reported that TNT would form salt with alcohol (conjugate base
of alcohol) under alkaline conditions generating Meisenheimer complex 16,17. After which,
TNT could react with NaClO to generate TNBCl and finally HNBB was formed, as
shown in Figure 2. The higher polarity the alcohol, the stronger alkaline the salt was,
which was beneficial for the formation of Meisenheimer complex. This mechanism could
be confirmed to be reliable by analyzing the relationship between pH value of solution
and yield of HNBB. As can be seen in Figure 3a, with different EA/EtOH ratios, highest
yield of HNBB also tended to be different. Moreover, in our reaction condition with
decreased EtOH ratio, high pH was required to obtain the best yield. In other words,
when the alcohol concentration was low, stronger alkaline condition would be helpful to
generate the RCH2Oꢀ intermediate 18,19. The process agreed with the mechanism we
mentioned above. This phenomenon was different from the one step reaction in which
too strong alkaline condition would reduce the reactivity and was not suggested. In a
word, alcohol not only played a role of solvent but also participated in the reaction.
< Insert Figure 2 here>
On the other hand, the choice of coꢀsolvent gave the opposite case. Generally, coꢀ
solvent of high polarity was unfavorable for the generation of HNBB, as in polar solvents
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significantly hindered, leading to high yield of HNBB. If solvents of too low dielectric
constant were used, however, reactions would be difficult to proceed due to the poor
solubility of TNT. So the ideal coꢀsolvent was found to be ethyl acetate/ethanol (1:2),
which owns a dielectric constant that close to but slightly higher than TNT to achieve
good solubility and reduce side reactions at the same time.
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3.1.2 The effect of pH
As analyzed in section 1.1, pH is an important factor that affects the reaction. The
reason lies in two aspects: 1) the formation of Meisenheimer complex; 2) the improved
stability of NaClO as well as activity. As shown in Figure 3b, the reaction went on slowly
under relatively low alkaline condition, which could be ascribed to low RCH2Oꢀ
concentration. Under high alkaline condition, TNT structure might be disrupted and
NaClO activity was decreased obviously. 21,22 In addition, different pH was required with
different coꢀsolvents. The optimized pH value was relatively low with coꢀsolvents of high
polarity. It was conjectured that coꢀsolvents of high polarity gave better waterꢀsolubility,
which promoted the reaction between OHꢀ in NaClO and TNT, so relatively low pH was
required. As shown in Figure 2, TNBCl was an important intermediate in the oxidation
process. This intermediate could be obtained only in THF solvent by adding HCl
(TNT:HCl = 3:1) to stop the reaction.18 In Figure 3b, highest yield of curve a and curve b
was obtained with completely the same pH value. The fact indicated that the pH mainly
participate in the first half of reaction mechanism in Figure 2 and affect the formation of
TNBCl.
< Insert Figure 3 here>
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3.2 Preparation of HNS
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The HNS preparation step was much more hazardous than that for HNBB because of
the employment of high toxic oxidant bromine in industry. 2,2,6,6ꢀtetramethylpiperidineꢀ
1ꢀoxyl (TEMPO) is commonly used as a radical catalyst for oxidation reactions due to its
high efficiency and selectivity. But their application in dehydrogenation was seldom
reported. In this work, HNS was prepared through aerobic dehydrogenation of HNBB in
a TEMPO/metal salts system.
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3.2.1 The influence of Solvent
Due to the importance of solvents, 23 different solvents were tried and the results were
listed in Table 1 for comparison. Almost no product was obtained in ethyl acetate or
benzene as HNBB could not be dissolved. Acetonitrile was not applicable for the
dehydrogenation of HNBB either, though it was usually used as solvent for oxidation of
alcohols catalyzed by TEMPO. 24 The volatile acetone could not give a satisfactory result
either due to its low boiling point. When amides (DMF and hexamethylphosphoramide)
or amine (cyclohexylamine) were used as solvents, a great quantity of byꢀproducts was
25,26
detected in HPLC with red viscous solid generated during experimental process.
So
after screening, DMSO was determined as the best solvent for dehydrogenation of HNBB.
The reasons were twofold. Firstly, DMSO could dissolve the substrate and catalyst
completely; and more importantly, bonding was achieved through sulfur or oxygen atom
with metal salts, which increased the activity of metal catalyst so as to accelerate the
reaction. 27,28 To further confirm this conclusion, sulfolane was used instead of DMSO,
giving almost no product.
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< Insert Table 1 here>
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Moreover, the influence of volume of DMSO was studied in detail. At least 5 mL of
DMSO was required to dissolve the substrate. The yield of HNS increased with further
addition of DMSO and a maximum yield was observed when 15 mL of DMSO was used.
The reaction efficiency would drop down if the amount of DMSO further increased. To
analyze the reason, crude products with DMSO of 10 mL and 25 mL were collected and
applied to HPLC. It was found that the contents of TNT in these two situations were of
0.01% and 40% respectively. So it was suggested that excessive solvent hindered the
contact between substrate and catalyst thus reduced the possibility of reaction.
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3.2.2 Evaluation of different catalytic system
Based on the combination forms of various catalysts shown in Table 2,
dehydrogenation process of HNBB was the result of both nitroxide radical and metal ions.
Some conclusions could be found:
1) Without nitroxide radical catalyst, no products or only poor yield of 10% could be
obtained with most metal salts under oxygen gas, except Pt2+ Cu+ and Fe2+. The addition
of TEMPO could increase the yield to about 20%.
2) When alkali metal or transition metal ions with no multiꢀvalance and low oxidation
capacity (K+, Mg2+ and Zn2+, entry 2 to 4) was used together with TEMPO, the yield
remains 20%. It showed that these metal ions had little effect on the dehydrogenation of
HNBB.
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3) Entry 5 and 6 showed that some metal ions like Pb2+ and Mn2+ could abstract the
secondary hydrogen ꢀCH2ꢀ of HNBB, but they were difficult to be oxidized by nitroxide
radical catalyst, so the yield with or without TEMPO was similar or just increased a little.
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4) Metal ions with multiꢀvalance but not strong oxidation capacity (Cr3+, Co2+, Ni2+, Cu+
and Fe2+, entry 7 to 11) exhibited catalytic performance together with TEMPO.
Comparing the performance with and without Cr3+, Co2+ and Ni2+, yields increased from
trace to 30~40%. It meant that Cr3+, Co2+ and Ni2+ could not be oxidized by oxygen
directly and TEMPO was essential in this process. While for Cu+ and Fe2+, they could be
oxidized by oxygen even though their catalytic efficiency was low, and the addition of
TEMPO could significantly improve the efficiency.
5) If another nitroxide radical catalyst NHPI was used instead of TEMPO (entry 11 and
12), the catalytic efficiency decreased slightly with conversion still remained over 60%.
The different catalytic activity was supposed to be the reason for different catalytic
performance.
6) As for ions of high valance such as Fe3+ and Cu2+ (entry 13 and 14), however, almost
no catalytic performance was exhibited. The results suggested that it was their oxides in
the form of M(III)OOꢀ that participated in the reaction instead of metal ion themselves.
The conclusion was further confirmed by the experimental results with N2 replacing O2
as shown in Figure 4.
< Insert Table 2 here>
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The details of experiment in Figure 4 were designed according to the catalytic
mechanism study about TEMPO 29ꢀ32 and results were shown as follow:
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1) TEMPO was used as the oxidizing agent under N2 gas, and three situations with no
(R1), catalytic amount (R2) and 1 equivalent amount (R3) of FeCl2 were tested. In all
cases, only 10% yield of HNS could be obtained. The results showed that O2 was the
oxidizing agent and source of O through the whole reaction.
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2) The dehydrogenation ability of TEMPO itself was limited in either N2 or O2
atmosphere (R1 and R5), while Fe2+ in N2 or O2 gas (R4 and R6) exhibited significantly
different performance. Combining 1) and 2), TEMPO was not the catalytic agent that
directly reacted with HNBB.
3) In R3, without O2, TEMPO/Fe2+ (or accurately Fe3+ formed) could not catalyzed the
reaction even equivalent amount of catalyst was added. It agreed with the result and
conclusions mentioned in Table 2 for entry 12 and 13. Fe3+ was also not the catalytic
agent in dehydrogenation.
4) The most possible mechanism was described in Figure 5. Fe2+ was first oxidized into
Fe(III)OOꢀ by O2 33, followed by the interaction with HNBB to generate HNS through
dehydrogenation. During this process, Fe(III)OOꢀ was reduced into Fe(II)OOH, which
would be activated again into Fe(III)OOꢀ by TEMPO. The role of O2 was to oxidize
TEMPOH to obtain TEMPO as active nitroxide radical.
< Insert Figure 4 and 5 here>
3.3 Enlargement and recycle of catalyst and solvent
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The main procedures for kilogramꢀleveled scaling up were shown in Scheme 2. Several
points could be generalized and shown as follows:
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1) Stirred batch reactor was employed in both steps. In the first step, due to the high
reaction rate and short reaction time, kenics static mixer was reported to be a good choice
and 40% HNS could be generated directly in this step. 34,35 Its advantage was continuous
flow and well mixed, however, low yield of HNS and difficulty and high cost in kgꢀ or
tonꢀsize scaleꢀup limited its industrial application.
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2) In the second step, pipe was used to introduce O2 into reaction solution. As the
dehydrogenation rate of HNBB was slow, the diffusion rate of O2 gas in solution was
faster than the reaction rate with the help of stirring, so there was no particular
requirement for gas dispersity.
3) All the solvent could be recovered by distillation, which would be discussed in detail
in the following part, and the residues were to be burned directly.
< Insert Scheme 2 here>
To provide reliable variation trend for larger scale production, two key points should be
considered during this process: massꢀtransfer effect and the recovery of solvent
containing catalyst.
3.3.1 The test of massꢀtransfer effect
During the scale up experiments of four magnitudes of 30, 100, 500 and 1000 grams as
shown in Table 3 to 6, no obvious heatingꢀup was found when HNBB and HNS were
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feeding, which suggested that thermal effect was relatively weak during the mixing
period. Besides, there was neither sudden cold nor fever observed during the reaction
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process, so the twoꢀstep reaction is not violently exothermic or endothermic. Due to the
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fast reaction rate for HNBB generation,
scaling up process would be influenced
obviously by diffusion effect. Extending reaction time was needed to obtain the same
yield. In contrast, the reaction rate was much lower for HNS and 10 hours were required
to complete the reaction. So it was almost free from the influence of diffusion effect.
3.3.2 The recovery of solvent containing catalyst
Ethyl acetate and alcohol were used as solvents for the synthesis of HNBB. More than
95% solvents could be recovered through distillation and reused without further treatment.
During the distillation process, small amount of water was also recovered together as
azeotrope. The water had little effect on the yield after a comparative test with
dehydrated solvent.
The solvent DMSO used for the preparation of HNS could not be distillated containing
the catalyst. So direct recycling was tried firstly. As shown in Table 6, the total yield after
5 times’ recycling was over 85.9% while it decreased to lower than 85% for the sixth
recycling, and the declining rate was growing. After analyzing of the solvent reused for
several times through HPLC, dozens of compounds were identified which may originated
from impurities in substrates and accumulation of byꢀproducts during the recycling
process. Considering the purity of product and rational use of raw materials, recycling for
5 times gave the best result. At this point, the recovery rate of DMSO was approximately
80%.
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An interesting phenomenon was observed that, after direct recycling of DMSO solvent
containing catalyst, the yield of HNS was much higher than 68% (Table 1 entry 10). It
was because the product HNS was partly dissolvable in DMSO. In the first cycle some of
the HNS product would stay in the DMSO solvent and form a saturated solution, which
showed a relative “low” yield. This saturated solution of HNS, which was reused directly
in later cycles, would dissolve no more HNS, and thus gave a real and high yield.
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60
During the 5 times’ recycling, small amount of TEMPO and FeCl2 would be washed
away or lost their catalytic activity. If they were not supplemented after each recycling,
the yield would deceased much more quickly, and less than 60% yield were obtained in
this situation (in Table s1~ s4 in supporting information).
< Insert Table 3,4,5 and 6 here>
4. Conclusion
In this paper, we reported a green approach for twoꢀstep synthesis of hexanitrostilbene
(HNS) and extended it by using a larger mixer, enabling the scale to be increased from 30
g to 1000 g of trinitrotoluene (TNT). In the intermediate hexanitrobienzyl (HNBB)
preparation step, mixed solvent ethyl acetate/ethanol (0.25mL/1.25mL per mmol of TNT)
was used instead of more expensive and toxic solvents THF/ethanol or benzene/ethanol
with pH controlled commercial NaClO as oxidant, giving the optimized yield over 80%.
Further investigation showed that polarity of mixed solvent and pH were two main
factors affecting the yield.
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In HNS preparation step, an effective catalytic system 2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀ
oxyl (TEMPO)/FeCl2 was used with oxygen in DMSO solvent. A complex of metal ion
and O2, donated as M(n+1)OOꢁ, was supposed to be the active agent that took part in the
reaction after analysis. TEMPO itself was difficult for the dehydrogenation of HNBB, but
could promote the formation of M(n+1)OOꢁ and assist the catalytic cycle.
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In order to investigate the feasibility of production, we increased the scale to kgꢀsize
under the same mixing condition. The yield of HNBB in the first step maintained over 80%
during the scaleꢀup process. In the second step, the total yields of pure HNS were more
than 85% after 5 times repeating before recovering the solvent and catalysts. The total
yield of the two steps would be more than 68%, and no other literatures had reported such
high yield. Besides, the avoiding of hazardous agents and recovery of catalysts and
solvent made this procedure extremely valuable for industry.
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FIGURES
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80
60
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20
Cosolvent
Solvent
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TNT
0
0
10
20
30
40
50
Dielectric constant
Figure 1. Synthesis of HNBB in different solvent/coꢀsolvent systems. Reaction condition
when changing cosolvent: TNT 4.4 mmol, NaClO (pH=13.5) 6.5 mL, ethanol 10.0 mL,
40 oC, 1 h; Reaction condition when changing solvent: TNT 4.4 mmol, NaClO (pH=13.5)
6.5 mL, ethyl acetate 5.0 mL, 40 oC, 1 h.
-
CH2Cl
NO2
CH2
CH3
NO2
O2N
O2N
NO2
O2N
NO2
Cl+(ClO-)
RCH2O-
NO2
NO2
RCH2OH
Cl-
OH-
H2O
O2N
H2 H2
C
NO2
C
NO2
O2N
O2N
NO2
Figure 2. Oxidation mechanism of TNT in alcohol solvent.
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a) THF
90
b) THF
d) Bezene
4
4
4
：
：
：
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7
8
90
80
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30
c) EA
80
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40
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30
12.8
13.2
13.6
14.0
12.4
12.8
13.2
13.6
14.0
pH of NaClO
pH of NaClO
Figure 3. The influence of pH of NaClO to HNBB preparation in different solvent.
Reaction condition in (a): TNT 4.4mmol, NaClO(pH=12.4~13.9) 6.5mL, 40oC, 30min; 4:
6, 4: 7 and 4: 8 stand for EA : EtOH = 4mL: 6mL, 4mL: 7 mL and 4mL: 8mL. Reaction
condition in (b): TNT 4.4mmol, Na ClO(pH=12.4ꢀ13.9) 6.5mL, 40oC, 30min. a) THF
20mL, EtOH 10mL; b) THF 20mL, EtOH 10mL, 1% w.t. HCl 200mL was added after
1min of reacting; c) EA 4mL, EtOH 8mL; d) Benzene 2mL, EtOH 8mL.
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R3
R4
R7
R2
R5
R6
R1
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0
TEMPOa
1:1
1:1
1:1
--
--
2:3
--
--
2:3
b
1:10
2:3 2:3
O2 O2
1:1 1:1
FeCl2
N2 N2
N2
N2
O2
Gas
Figure 4. Evaluation the role of each element in catalytic system. Reaction condition:
HNBB 2.2mmol, DMSO 10 mL, 55oC, 8 h, gas 1 atm. a) TEMPO: HNBB (mmol:
mmol); b) FeCl2: HNBB (mmol: mmol).
Figure 5. Dehydrogenation mechanism of HNBB with TEMPO/Fe2+/O2.
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SCHEMES
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Scheme 1. Preparation method of HNS reported in previous works.
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Scheme 2. Process of HNS preparation from TNT in scaleꢀup production.
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TABLES.
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Table 1. The influence of solvents in dehydrogenation of HNBB a
Entry Solvent Volume (mL) Yield of HNS (%)
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1
Ethyl acetate
20
ꢀꢀ
2
Benzene/ethanol 15/15
ꢀꢀ
3
DMF
15
ꢀꢀ
4
[(CH3)2N]3PO b 20
trace
ꢀꢀ
c
5
(CH2)4SO2
C6H11NH2
acetone
20
20
15
20
5
d
6
ꢀꢀ
7
12.3
17.9
43.2
68.7
49.4
8
Acetonitrile
DMSO
9
10
11
DMSO
15
25
DMSO
a) Reaction condition: HNBB 2.2mmol, TEMPO 0.13mmol, FeCl2ꢁ7H2O 0.14mmol,
55oC, 8 h, O2 1 atm. b) Hexamethylphosphoramide; c) Tetramethylene sulfone; d)
Cyclohexylamine
Table 2. The influence of different metal salts on HNS preparation with/without TEMPO.
Entry Metal salts
Yield of HNS (%)
With
Without
TEMPO a TEMPO b
1
2
3
4
5
ꢀꢀ
21.4
21.0
24.9
21.8
trace
9.1
Na2CO3
MgSO4ꢁH2O
ZnCl2ꢁ7H2O
10.9
11.9
21.0
Pb(CH3COO)2ꢁ3H2O 22.9
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MnSO4ꢁH2O
CrCl3ꢁ4H2O
39.8
37.8
39.8
32.9
62.7
81.0
60.1 d
trace
9.9
21.0
trace
trace
trace
34.9
20.6
20.9
trace
9.0
7
c
8
Co(acac)2
9
NiCl2ꢁ6H2O
CuCl
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14
FeCl2ꢁ7H2O
FeCl2ꢁ7H2O
CuCl2ꢁH2O
FeCl3
a) Reaction condition: HNBB 2.2mmol, metal salts 0.14 mmol, TEMPO 0.13mmol,
DMSO 10 mL, 55oC, 8 h, O2 1 atm. b) TEMPO was not added in these reactions. c)
Co(acac)2 was short for Cobalt(II) acetylacetonate. d) NHPI was used instead of TEMPO
with the same moles.
Table 3. Scaled result of HNBB synthesis.
Entry
TNT / g
30
HNBB / g
24.3
Yield / %
81.3
m. p. / oC
216~218
216~218
215~217
216~218
Purity / % a
99.9
1
2
3
4
100
79.3
80.8
99.9
500
392.9
818.7
80.2
99.8
1000
81.5
99.9
a: determined by HPLC with both UV and differential refractometer detector.
Table 4. Recycle of catalyst and solvent in 100g HNS synthesis
Entry DMSO / mL TEMPO / g FeCl2 / g HNS / g m. p. / oC
1000 2.5 4.5 52.2 316~317.5
Purity / % a
99.8
1
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40
45
70
70
75
0.5
0.5
0.5
0.5
0.5
3.5
2.5
2.5
2.5
2.5
115.2
93.9
89.7
87.6
80.0
316~317.5
315.5~317.5
315.5~317.5
315~317
99.9
99.8
99.6
99.5
99.5
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315~317
Total yield: 86.1% (5 recycles); 85.2% (6 recycles).
a: determined by HPLC with both UV and differential refractometer detector.
Table 5. Recycle of catalyst and solvent in 500g HNS synthesis
Entry DMSO / mL TEMPO / g FeCl2 / g HNS / g m. p. / oC
Purity / % a
99.8
1
2
3
4
5
6
4500
280
260
500
450
400
10.0
2.0
2.0
2.0
2.0
2.0
15.0
10.0
10.0
10.0
10.0
10.0
256.7
496.1
389.9
340.0
332.1
312.1
316~317.5
316~317.5
316~317.5
315~317
99.8
99.7
99.6
315~317
99.5
315~317
99.5
Total yield: 85.1% (5 recycles); 84.3% (6 recycles).
a: determined by HPLC with both UV and differential refractometer detector.
Table 6. Recycle of catalyst and solvent in 1000g HNS synthesis
Entry DMSO / mL
TEMPO / g
20.0
FeCl2 / g
35.0
HNS / g
655.9
m. p. / oC
316~317.5
316~317.5
315~317
Purity / % a
99.8
1
2
3
8000
900
5.0
25.0
936.0
99.8
500
5.0
25.0
763.1
99.6
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700
720
690
5.0
5.0
5.0
25.0
25.0
25.0
694.3
688.8
637.8
315~317
315~317
314~316.5
99.6
99.5
99.3
9
Total yield: 85.9% (5 recycles); 84.8% (6 recycles).
a: determined by HPLC with both UV and differential refractometer detector.
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ASSOCIATED CONTENT
Supporting Information.
Experimental data of recovery of solvent and catalysts in scaleꢀup was listed in Table s1,
s2, s3 and s4.
AUTHOR INFORMATION
Corresponding Author
* Pengcheng Wang Tel.: +86 02584315030. Fax: +86 02584315030, Eꢀmail:
alexwpch@mail.njust.edu.cn.
** Ming Lu Tel.: +86 02584315030. Fax: +86 02584315030, Eꢀmail:
luming@mail.njust.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The authors greatly acknowledge the National Natural Science Foundation of China
(NSFC, Grant No. 51374131 and U1530101) for supporting this work.
REFERENCES
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