Scalability of a Time- And Cost-Effective Procedure for the Synthesis of Picryl Bromide

Article abstract of DOI:10.1021/acs.oprd.9b00313

An optimized synthetic procedure for the manufacture of picryl bromide on a 300 g scale is described. Previous procedures had different drawbacks such as two or more separate nitration steps with varying mixed acids, a complicated workup and purification

Full text of DOI:10.1021/acs.oprd.9b00313

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Communication
Scalability of a Time- and Cost Effective
Procedure for the Synthesis of Picryl Bromide
Thomas Matthias Klapoetke, and Dominik Ernst Dosch
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.9b00313 • Publication Date (Web): 09 Aug 2019
Downloaded from pubs.acs.org on August 9, 2019
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Scalability of a Time- and Cost Effective
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Procedure for the Synthesis of Picryl Bromide
Thomas M. Klapötke* and Dominik E. Dosch
Energetic Materials Research, Department of Chemistry, Ludwig-Maximilian University
Munich, Butenandtstr. 5–13 (D), 81377 Munich, Germany
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ABSTRACT: An optimized synthetic procedure for the manufacturing of picryl bromide in a
300 g scale is described. Previous procedures had different drawbacks such as two or more
separate nitration steps with varying mixed acids, a complicated workup and purification
procedure, expensive starting materials or very long reaction times. An optimized and time
efficient method on a laboratory scale was described in an earlier conference contribution.
The one-pot nitration of bromobenzene using a 5:1 mixed acid, consisting of oleum (30%)
and white-fuming nitric acid (ten equivalents) was developed to prove the technical scalability
of the reaction. By applying the optimized reaction parameters to a large scale environment,
yields of up to 72% of crude picryl bromide can be achieved. The product contains only a
minor picric acid impurity (2-3%), which is formed during the aqueous workup step. It can be
removed by a single recrystallization from boiling chloroform, to facilitate the target
compound in pure form. This method combines the use of cheap materials with a time-
efficient route of synthesis and a simple purification step, which is an improvement compared
to the state of the art methods.
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KEYWORDS: picryl bromide, energetic materials, 1-bromo-2,4,6-trinitrobenzene, synthesis.
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Introduction
Picrylbromide or 1-bromo-2,4,6-trinitrobenzene (MBTNB) is a versatile building block for
the synthesis of various energetic materials. Because bromide represents an excellent leaving
group, it can be used analogously to picryl chloride to transfer the picryl moiety within a wide
variety of nucleophilic substitution reactions. Another relevant application for MBTNB is the
manufacturing of highly thermostable explosives belonging to the group of
polynitropolyphenylenes like 2,2',2'',4,4',4'',6,6',6''-nonanitro-1,1':3',1''-terphenyl (NONA) or
2,2',2'',2''',4,4',4'',4''',6,6',6'',6'''-dodecanitro-1,1':3',1'':3'',1'''-quaterphenyl (DODECA). They
utilize the copper-mediated Ullmann-reaction for the formation of carbon-carbon bonds
between polynitroarenes, which contain a halogen function as the leaving group.1, 2 Another
relevant use of MBTNB is its application in kinetic and mechanistic studies.3 In the past
various synthetic pathways towards MBTNB were developed and investigated. All of them
show significant drawbacks for an industrial scale application, with the key concerns being
the price of the used materials2, 4, problematic solvents5, the reaction time6 or various
additional purification steps, which complicate the manufacturing process of larger amounts
of high purity MBTNB. The first route of synthesis uses expensive, toxic and explosive picric
acid as a starting material and PBr3 as bromination agent2 to yield MBTNB. A mixed solvent
system consisting of DMF and toluene is applied, which is problematic for large scale
productions because DMF is on the REACH candidate list.5 A second synthetic pathway
towards MBTNB starts from bromobenzene and a cheap mixed acid system involving a two-
step nitration. The combined reaction time of 29 hours and the necessity to isolate the
intermediate dinitrobromobenzene isomers make this method very inefficient regarding time
and workforce.6 Another synthesis method starts from trinitroanisole, which is not
commercially available in larger amounts, which is a disadvantage for large scale synthesis. It
is subjected to a two-step bromo-demethoxylation reaction, using KI/EtOH and PBr3 as the
key reagents.4 This pathway is therefore not suitable for synthesis exceeding the laboratory
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scale. The only competitive method for the synthesis of MBTNB starts from bromobenzene
and utilizes potassium nitrate and oleum (30%) as the nitration agents at an elevated
temperature of 125 °C. According to the literature the overall yield is 60% and this reaction
requires 6 hours and an additional purification step of recrystallization from boiling ethanol to
remove byproducts.2 When considering all the mentioned drawbacks, the development of an
optimized and time efficient synthesis of MBTNB on a technical scale is necessary, to
facilitate and stimulate the use of this interesting starting material in the energetic materials
community.
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Results and Discussion
Synthetic Approach. To overcome the problems mentioned previously, the synthesis of
MBTNB has been optimized according to Scheme 1 on a laboratory scale. After this
procedure had been reproduced several times on a 25 g scale, it was scaled up to 300 g scale
to prove the scalability of the procedure.
Scheme 1. Optimized synthetic route for MBTNB7
Br
Br
O2N
NO2
30% Oleum / 100% HNO3
45 min, 25 °C
2 h, 130 °C
NO2
Earlier experiments during the optimization process showed unwanted byproducts like
dinitrobenzene and multi-brominated benzene derivatives, which formed at temperatures over
140 °C.7 Their formation is avoided by choosing a programmed temperature. The utilized 5:1
mixed acid is potent enough to introduce the first nitro group at 25 °C and the reaction
temperature of 130 °C is optimal for the fast and selective introduction of the two remaining
nitro groups. Following this temperature program, the manufacturing of highly pure MBTNB
in a time and cost efficient way with cheap starting materials and a good yield of 72% on a
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technical scale was realized. Compared to the laboratory scale, using a thermocouple and an
aluminum heating-block for temperature control,7 the yield can be further increased by 9%
during scale up using the 5 liter reactor. Hydrolysis of 2-3% of MBTNB during the workup
procedure leads to minor picric acid impurities, which have to be removed by recrystallization
from chloroform. No other impurities are formed during synthesis, which is another
advantage of the new process.
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Conclusions
It was shown, that the proposed optimized route for the synthesis of MBTNB is a scalable,
time- and cost-effective way to manufacture the target compound with good yields and high
purity. The presented synthetic route is a significant improvement and can lead to a broader
use of MBTNB as a building block for new energetic materials.
Experimental Section
General. Solvents, deuterated solvents for the NMR experiments and all further chemicals
were used as received from the suppliers, without further purification. The reactions were
conducted in a Diehm 5 L jacketed glass reactor, equipped with a CAT R100C-T overhead
stirrer and a Lauda Integral XT 250 W process thermostat. NMR spectra were recorded with a
Bruker 400 or Bruker 400 TR at ambient temperature. The chemical shifts were determined
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with respect to external standards, Me4Si (1H 399.8 MHz; C 100.5 MHz) and MeNO2 (14N
28.9 MHz). Infrared spectra were measured with a PerkinElmer Spectrum BX-FTIR
spectrometer equipped with a Smiths DuraSamplIR ATR device. Raman spectra were
recorded in a glass tube with a Bruker MultiRAM FT-Raman spectrometer with ND:YAG
laser with excitation up to 1000 mW at 1064 nm in the range 4000–400 cm−1. All spectra
were recorded at ambient temperature. The C/H/N content was determined with an Elementar
vario EL or Elementar vario micro cube instrument. The sensitivities towards impact and
friction were determined with a BAM drophammer8 and a BAM friction tester.9 The
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sensitivity towards electrostatic discharge was determined with an electric spark tester from
OZM. The melting range was determined with an Büchi Melting Point B-540 device and a
heating rate of 1 °C per minute.
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Caution! 1-bromo-2,4,6-trinitrobenzene (MBTNB, picryl bromide) itself is considered a
sensitive material and therefore should be handled with caution during synthesis or
manipulation, and additional protective equipment (leather jacket, face shield, ear protection,
Kevlar gloves) is strongly recommended.
300 g reactor scale: A 5 L glass jacketed reactor was charged with oleum (1.3 L, 65%
SO3), which was cooled to 5 °C with external cooling by a process thermostat. Then sulfuric
acid (1.6 L, 96%) was added during one hour, whilst the temperature was kept below 40 °C.
Afterward white fuming nitric acid (576 mL, 13.8 mol, 10 eq) was added in small portions
while keeping the temperature below 25 °C. After cooling to 5 °C, bromobenzene (143.2 mL,
1.38 mol, 1 eq) was slowly added to the mixture and the temperature was kept below 20 °C
during the addition. The reaction mixture was then stirred at 25 °C for 45 minutes, followed
by heating to 130 °C for two hours. The mixture was cooled to 20 °C, and then quenched by
adding a total of 5.7 kg of ice. The mixture was separated in five smaller batches and the solid
white precipitate was removed by filtration. The product was washed with cold water until the
precipitate runs acid-free. After drying, the crude product weighs 287 g (0.98 mol, 72%) with
2-3% of picric acid as a hydrolysis byproduct, which could be easily removed by
recrystallization from boiling chloroform.
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1H-NMR: 8.75 ppm; C-NMR: 115.1, 122.2, 147.0, 152.1 ppm; N-NMR: -19.8, -24.0
ppm; Melting Point: 122 – 124 °C; IR (ATR): ṽ = 3082 (m), 1846 (w) 1599 (m), 1532 (s),
1411 (w), 1344 (s), 1197 (m), 1047 (s), 925 (s), 824 (m), 743 (s), 716 (s), 491 (m), 413 (w)
cm-1; Raman (300 mW): ṽ = 3090 (13), 1596 (37), 1542 (16), 1381 (18), 1348 (100), 1199
(12), 1047 (36), 823 (26); Elemental Analysis: Calculated: C, 24.68; H, 0.69; N, 14.39
Experimental: C, 24.70; H, 0.75; N, 14.09; Sensitivities: BAM drop hammer: 40 J (<100
μm); Friction tester: >360 N (<100 μm); ESD: 0.5 J (<100 μm).
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Associated content
Supporting Information. The Supporting Information is available free of charge on the
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ACS Publications website at DOI:
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1H, 13C, 14N NMR spectra (PDF)
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Author information
Corresponding Author. *E-mail: tmk@cup.uni-muenchen.de
Notes. The authors declare no competing financial interest.
Author Contributions
The manuscript was written through contributions of all authors. All authors have given
approval to the final version of the manuscript.
Acknowledgments
For financial support of this work by the Ludwig-Maximilian University of
Munich (LMU), the Office of Naval Research (ONR) under grant no.
ONR.N00014-16-1-2062
and
the
Strategic
Environmental
Research
and
Development Program (SERDP) under contract no. WP19-1287 are gratefully
acknowledged. The authors also thank Mr. Maurus Völkl, Mr. Stefan Huber and Dr. Marc
Bölter for help regarding the handling of the reactor and Ms. Theresa Küblböck for help with
the graphics.
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