A Chlorine Gas-Free Synthesis of Dichloroglyoxime

Article abstract of DOI:10.1021/acs.oprd.6b00252

A new procedure for the synthesis and isolation of dichloroglyoxime is discussed. This material has historically been synthesized from glyoxime and elemental chlorine gas. Chlorine gas is difficult to handle and control in the laboratory and has a high toxicity profile. Our method for making dichloroglyoxime in high purity uses glyoxime and N-chlorosuccinimide in DMF, with a lithium chloride-based workup. Overall yields are comparable with those obtained using the procedure involving the use of chlorine gas.

Full text of DOI:10.1021/acs.oprd.6b00252

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Communication
A Chlorine Gas-Free Synthesis of Dichloroglyoxime
Leah A Wingard, Pablo E Guzman, and Jesse James Sabatini
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.6b00252 • Publication Date (Web): 29 Aug 2016
Downloaded from http://pubs.acs.org on August 30, 2016
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A Chlorine GasꢀFree Synthesis of Dichloroglyoxime
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b
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a
Leah A. Wingard , Pablo E. Guzmàn , Jesse J. Sabatini*
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US Army Research Laboratory, Energetics Technology Branch, Aberdeen Proving Ground, MD
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1005, United States
b
Oak Ridge Associated Universities, Belcamp, MD 21017, United States
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Table of Contents
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ABSTRACT
A new procedure for the synthesis and isolation of dichloroglyoxime is discussed. This material
has historically been synthesized from glyoxime and elemental chlorine gas. Chlorine gas is
difficult to handle and control in the laboratory, and has a high toxicity profile. Our method for
making dichloroglyoxime in high purity uses glyoxime and Nꢀchlorosuccinimide in DMF, with a
lithium chlorideꢀbased workꢀup. Overall yields are comparable with those obtained using the
procedure involving the use of chlorine gas.
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KEYWORDS: Dichloroglyoxime, chlorination, lithium chloride, “green” chemistry, energetic
materials
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INTRODUCTION
Dichloroglyoxime (DCG) is an important building block that has found wide application
toward the synthesis of numerous energetic materials. This includes the 5,5’ꢀbisꢀtetrazoleꢀ
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1,1’diolꢀbased materials ABTOX as well as TKXꢀ50 , and 3,3’dinitraminoꢀ4,4’ꢀbisꢀfurazan.
Further applications of DCG include the synthesis of iridiumꢀ and rheniumꢀbased luminescent
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3,3’ꢀbis isoxazole complexes , polynucleating ligand systems, and their complexes of dꢀmetals.
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DCG is most commonly prepared according to Scheme 1. Elemental chlorine gas is bubbled
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through a stirred suspension of glyoxime in ethanol at ꢀ20 C for 30 min. After evaporation of
EtOH under reduced pressure, chloroform is added to wash the crystals. DCG is then isolated by
filtration in 77ꢀ97% yield.
Scheme 1. Historical synthesis of dichloroglyoxime.
Results and Discussion
The issue with the historical synthesis of DCG centers on the use of chlorine gas. Chlorine
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gas has a high toxicity profile , is a difficult reagent to handle, and its addition is difficult to
control. Hydroximoyl chlorides have also been synthesized from aldoximes by using Nꢀ
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chlorosuccinimide (NCS) in DMF . The use of NCS is advantageous over chlorine gas because
NCS is an easilyꢀhandled solid that is convenient for controlled addition while minimizing the
inhalation hazard. As summarized in Scheme 2, a synthetic procedure to make DCG from
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glyoxime by the NCS/DMF method was recently reported . According to this procedure, it is
reported that pure DCG is obtained in 97% yield. However, despite several attempts to
reproduce the procedure, we were unable to obtain a pure product. As per the reported procedure,
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the reaction mixture is diluted with water when complete, and the product is extracted with Et O.
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After evaporation of the solvent, attempted recrystallization from boiling toluene afforded a
white crystalline material in the reported 97% yield. This material, however, is not pure DCG,
but is an inseparable complex of DCG and DMF in the molar ratio of 1.4:1 (see supporting
information). Thus, the actual yield of DCG by this procedure is only 55%.
Scheme 2. Initial process of dichloroglyoxime synthesis employing NCS and DMF.
In an effort to obtain DCG in high purity, an alternative workꢀup was developed (Scheme 3).
After the reaction was complete, as much DMF as possible was removed with the aid of a rotary
evaporator. The resulting solid was dissolved in EtOAc, and this solution was washed three times
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with a 5% aqueous LiCl solution . This was sufficient to remove nearly all the residual DMF.
EtOAc was removed under pressure to afford a crude white solid. This white solid was
suspended in water and stirred vigorously for 30 minutes. During this time, the water turned
green. The solid was filtered and airꢀdried overnight to afford a 75% yield of DCG as a white
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powder in high purity, as observed by H NMR analysis. A sample of DCG prepared by this
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method was shown by DSC analysis to melt with exothermic decomposition at 203 C, which is
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in excellent agreement with the literature (see supporting information) . Our method avoids the
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use of halogenated solvents such as chloroform, highly flammable Et O, and the need for
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recrystallization from carcinogenic toluene.
Scheme 3. New process for the synthesis of dichloroglyoxime.
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Conclusions
In summary, an improved process for the synthesis of DCG without employing chlorine gas
has been developed. The new method provides a product of high purity in 75% yield. Although
a previous method to make DCG from glyoxime and NCS was reported, this method involved
the use of highly flammable and volatile Et O and carcinogenic toluene to afford an inseparable
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complex of DCG and DMF in the molar ratio of 1.4:1 . The new method involves a LiClꢀbased
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workꢀup to provide DCG in high purity as determined by H NMR analysis. This “greener”
synthetic method of DCG can be used toward synthesizing numerous materials based on 3,3’ꢀ
bisꢀisoxazoles, 5,5’ꢀbisꢀtetrazoleꢀ1,1’ꢀdiol, and 3,3’ꢀdiaminoꢀ4,4’ꢀbisꢀfurazans.
Experimental Section
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Chemicals and solvents were used as received from SigmaꢀAldrich. H and C NMR spectra
were recorded using a Bruker 400 MHz and 100 MHz instrument, respectively. The chemical
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shifts quoted in ppm in the text refer to typical standard tetramethylsilane ( H, C) in DMSOꢀd
as the solvent. Melting points and decomposition temperatures were measured at a heating rate
of 5°C/min using a TA instruments Q10 DSC instrument. Infrared spectra were measured with a
Bruker AlphaꢀP FTIR instrument.
Caution: Though no accidents occurred during our synthesis of dichloroglyoxime, glyoxime
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should be handled with care due to its reported thermal and shock sensitivity.
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Dichloroglyoxime (2)
To a 1000 mL roundꢀbottom flask equipped with a mechanical stir bar was added glyoxime (30.0
g, 0.341 mol, 1.00 eq) and 340 mL of DMF. After the glyoxime dissolved, the solution was
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cooled to 0 C in an ice bath, and Nꢀchlorosuccinimide (97.5 g, 0.716 mol, 2.10 eq) was added in
eight equal portions over 2 h. After the final portion was added, the reaction mixture was stirred
overnight while the ice bath slowly warmed to room temperature. As much DMF as possible
was removed under reduced pressure with the aid of a rotary evaporator at 70 C. The crude solid
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was dissolved in 400 mL of EtOAc, and the resulting organic phase was washed with a 5%
aqueous solution of LiCl (3 x 333 mL). The organic extract was dried over magnesium sulfate
and filtered. EtOAc was removed under reduced pressure with the aid of a rotary evaporator at
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0 C to afford a crude white solid. The solid was suspended in 700 mL of water, and was stirred
vigorously for 30 minutes. During this time, the water color changed from colorless to green.
The white solid was filtered with the aid of a fritted funnel, and was left under suction for 1 h.
This material was airꢀdried overnight in a fume hood to yield 40.1 g (75%) of dichloroglyoxime
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(2) as a fine white powder. m.p. (dec.) = 203 C; IR: ν = 3243 (s) cm , H NMR (400 MHz,
OH
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DMSOꢀd ), δ 13.1 (s, 2H, ꢀNOH), C NMR (100 MHz, DMSOꢀd ), δ 130.7.
Supporting Information
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The DSC analysis of glyoxime, the H NMR spectra, C NMR spectra, IR spectra, and the DSC
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analysis of dichloroglyoxime, and the H NMR spectrum of the 1.4:1 dichloroglyoxime:DMF
complex is provided in the supporting information. This material is available free of charge via
the Internet at http://pubs.acs.org.
Corresponding Author
*Eꢀmail: jesse.j.sabatini.civ@mail.mil; Phone: 410ꢀ278ꢀ0235
Author Contributions
The manuscript was written through contributions of all authors. All authors have given approval
to the final version of the manuscript.
Funding Sources
Research sponsored by the Army Research Laboratory was accomplished in part under
Cooperative Agreement Number W911NFꢀ12ꢀ2ꢀ0019. The views and conclusions contained in
this document are those of the authors and should not be interpreted as representing official
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policies, either expressed or implied, of the Army Research Laboratory or the U.S. Government.
The U.S. Government is authorized to reproduce and distribute reprints for Government purposes
notwithstanding any copyright notation herein.
ACKNOWLEDGMENT
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The authors are indebted to the US Army for financial support in carrying out this work.
ABBREVIATIONS
Cl = chlorine; EtOH = ethanol; CHCl = chloroform; NCS = Nꢀchlorosuccinimide; DMF =
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dimethylformamide; Et O = diethyl ether; EtOAc = ethyl acetate; DCG = dichloroglyoxime
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REFERENCES
1. Klapötke, T. M.; Fischer, N.; Fischer, D.; Piercey, D. G.; Stierstorfer, J.; Reymann, M. US
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. Frontier, A. “Not Voodoo X;”
http://chem.chem.rochester.edu/~nvd/pages/workup.php?page=solvent_workup, accessed
August 17, 2016. It is well established that DMF can be removed in the workꢀup by washing
with a 5% aqueous solution of LiCl. Other metal chloride salts (i.e. NaCl) were not
attempted.
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