Neutralization of a Toluene Waste Stream Containing Thionyl Chloride

Article abstract of DOI:10.1021/acs.oprd.7b00195

Neutralization of thionyl chloride in toluene was found to be ineffective with water. A solution is to use an excess of a soluble reagent to consume the thionyl chloride. Butanol was shown to convert thionyl chloride to n-butyl sulfite and hydrogen chloride. An aqueous workup removes any residual hydrogen chloride.

Full text of DOI:10.1021/acs.oprd.7b00195

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Communication
Neutralization of a Toluene Waste Stream Containing Thionyl Chloride
John Robert Durrwachter
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00195 • Publication Date (Web): 08 Aug 2017
Downloaded from http://pubs.acs.org on August 10, 2017
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Neutralization of a Toluene Waste Stream Containing Thionyl Chloride
J. Robert Durrwachter*
th
New Product Development, Cambrex Charles City, Inc., 1205 11 Street, Charles City, Iowa,
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ABSTRACT:
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Neutralization of thionyl chloride in was found to be ineffective with water. A solution is to use
an excess of a soluble reagent to consume the thionyl chloride. Butanol was shown to convert
thionyl chloride to nꢀbutyl sulfite and hydrogen chloride. An aqueous workup removes any
residual hydrogen chloride.
Keywords: thionyl chloride, neutralization, safety, waste
Background.
Waste is an integral part of chemical processing and multiꢀstep complicated batch processes
are often fraught with high waste to product ratios. Waste issues are typically more logistical
and regulatory rather than chemical. However, there are cases where the waste presents a
significant safety or disposal issue that requires a chemical resolution. Although neither
glamorous nor sophisticated, solving waste issues is a necessary and sometimes challenging task.
This waste stream originated from a process that converted an αꢀhydroxy amine to the
corresponding αꢀchloro amine hydrochloride with a 10ꢀ20% excess of thionyl chloride (Scheme
1). The product of interest precipitates almost quantitatively, leaving behind a dilute solution of
thionyl chloride in toluene. Disposal of the flammable, reactive, and corrosive waste presented
an unexpected challenge.
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Scheme 1. Reaction of thionyl chloride with an αꢀhydroxy amine
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Development.
Simply disposing of the waste into the onꢀsite organic waste tanks was undesirable since the
thionyl chloride would react vigorously with alcohols, amines and water. Besides having an
uncontrolled chemical reaction taking place inside of a waste tank, this would generate hydrogen
chloride that could be corrosive to the 316 stainless steel material of construction (MOC) of
these tanks. It seemed prudent to neutralize the thionyl chloride before disposing of the waste.
The original notion for neutralizing the excess thionyl chloride was a simple aqueous sodium
hydroxide quench, where the toluene waste stream and dilute aqueous sodium hydroxide were
mixed together at ambient temperature. Bretherick’s indicates there are issues with this
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approach. The monograph points out that in one case, this led to disposal of a toluene solution
with active thionyl chloride still present that reacted in an uncontrolled manner in another vessel.
Bretherick’s indicates the agitation in the example was inadequate and suggests “extremely good
agitation” as a solution. However, when this approach was implemented in the large scale
production of this product, the thionyl chloride was still unquenched.
Reagents such as thionyl chloride and its phosphoꢀanalog phosphorus oxychloride are
commonly used in organic synthesis, e.g., in converting carboxylic acids to acid chlorides and
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alcohols to chlorides. However, their reactivities are often underappreciated. For example,
when a waste stream containing thionyl chloride in ethyl acetate was drummed without
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neutralization a runaway reaction took place. Thionyl chloride has been shown to react
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3,4
exothermically with DMF, THF, and MTBE.
Similarly, phosphorus oxychloride can react
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exothermically with acetone. In one hazard study, it was shown that partially hydrolyzed
phosphorus oxychloride can react unexpectedly after a period of time even in the presence of a
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large excess of H O if there is no pH control. This latter investigation developed analytical
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methods ( P NMR and Raman spectroscopy) to track the intermediates and determine when the
hydrolysis was complete so the waste could be safely discarded.
After the failure to adequately neutralize the unreacted thionyl chloride in the production run,
an investigation was initiated to explore the apparent lack of reactivity of thionyl chloride with
water. The initial challenge was to analyze for thionyl chloride as there was no process related
analytical method for thionyl chloride and developing one would have been detrimental for the
project timeline. Although observation of ‘smoke’ when the solution was exposed to air was
satisfactory for the production scale filtrate to indicate the presence of thionyl chloride,
something more quantitative was needed for this effort. Although gas evolution is measurable,
the method of choice was to measure a change in pH. Treatment of an aliquot of the thionyl
chloride solution with deionized water would show a sharp drop in pH if thionyl chloride was
present; monitoring the change in pH in this manner is a rapid, semiꢀquantitative assay. For this
investigation, the pH change approach was used in nearly every case to determine the presence
of thionyl chloride.
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The logic behind the plan to quench the thionyl chloride was to take advantage of the products
of hydrolysis. Each mole of thionyl chloride reacts with water to form one mole of sulfur
dioxide and two moles of hydrogen chloride (Scheme 2); both products are gases, but the
hydrogen chloride should stay in the reaction’s aqueous phase. The sulfur dioxide would likely
be driven overhead into the high pH scrubber system and neutralized to form a dilute solution of
sodium sulfite. The scrubber waste is usually disposed by transferring directly to the onꢀsite
waste water treatment plant. One issue with this approach would be the inadvertent mixing of
this stream with an acidic stream which would drop the pH and possibly release sulfur dioxide
gas. This can easily occur when waste streams from multiple processes are mixed. However,
this is minimized in this case as the solution is rather dilute. The hydrogen chloride left in the
aqueous phase of the reaction mass would be readily handled by direct neutralization with
sodium hydroxide.
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Scheme 2. Hydrolysis and neutralization of thionyl chloride
With the pH change analytical tool in hand, the laboratory investigation began and the first
effort to neutralize the thionyl chloride focused on reacting the thionyl chloride/toluene stream
with water at an elevated temperature to accelerate the reaction. Even after heating to 90 °C for
1½ hours and extraction with dilute sodium hydroxide, addition of deionized water demonstrated
a sharp drop in pH, indicating unreacted thionyl chloride was present.
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To evaluate the effect of a surfactant, an acid stable surfactant CIP 200 was added to water to
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treat the thionyl chloride in toluene. This too was heated to 90 °C and stirred for 24 hours, but
the next day, the reaction mass was visibly offꢀgassing, a positive indication of thionyl chloride.
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It would seem the problem with water as the quenching reagent for thionyl chloride is the
mutual lack of solubility of both compounds in the other solvent. Water has very low solubility
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in toluene (0.03% at 20 °C) while thionyl chloride apparently has no affinity for water. This
latter point was surprising, given the rapid reaction neat thionyl chloride has when added directly
to water. Thionyl chloride is evidently quite lipophilic.
The key to quenching thionyl chloride then would be to use a toluene soluble reactant.
Thionyl chloride reacts with many substrates, but an alcohol is a very convenient reactant and
produces an organic product completely soluble in the toluene system. The choice was made for
nꢀbutanol (bp 116 – 118 ºC) as it was already available onꢀsite and should react with thionyl
chloride to form the requisite gases sulfur dioxide and hydrogen chloride, and relatively
nonvolatile 1ꢀchlorobutane (bp 77 – 78 ºC). 1ꢀChlorobutane was compatible as a component of
the resultant waste stream for offꢀsite disposal and the two gases can be readily neutralized with
an aqueous workup.
To pursue this, an excess of nꢀbutanol was added to a solution of thionyl chloride in toluene,
heated to reflux to drive out the sulfur dioxide and hydrogen chloride, cooled and extracted with
aqueous sodium hydroxide, and finally water. This time, the pH of the final water wash was
stable, indicating no active thionyl chloride. This process was further demonstrated on a
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combined sample of filtrate and wash from laboratory scale processing experiments. The best
process for neutralizing the thionyl chloride waste stream incorporated an excess of nꢀbutanol
relative to a full charge of thionyl chloride.
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To further investigate this improved analytical methods were utilized to fully characterize the
neutralization reaction. Gas chromatography was initially evaluated to quantify the 1ꢀ
chlorobutane and nꢀbutanol in a quenched toluene/thionyl chloride reaction mass that used 90%
excess of butanol relative to thionyl chloride. The results were surprising, as the levels of both
1ꢀchlorobutane and nꢀbutanol were estimated to be less than 0.1% w/w, when they should have
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been in the 3% w/w range. Further, the relative peak areas on the chromatogram were expected
to be about the same but they were not. Rather, the 1ꢀchlorobutane peak was less than 5% of the
area of the nꢀbutanol peak; based on the stoichiometry of the proposed chemistry they should
have been nearly the same area.
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H NMR was then used to analyze the thionyl chloride neutralization reaction mass and it
confirmed the gas chromatography findings; nꢀbutanol was estimated at 0.04% and there was no
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detectable butyl chloride. It also identified the actual product of the neutralization to be nꢀbutyl
sulfite, not 1ꢀchlorobutane; see Scheme 3. The literature precedent on this is well established; an
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excess of alcohol will lead to the formation of a sulfite ester and not the alkyl chloride.
Scheme 3. Reaction of Thionyl Chloride with an excess of nꢀButanol
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H NMR estimated the concentration of nꢀbutyl sulfite to be 7.6%; the expected concentration
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is 7.85%, indicating very good agreement. The discovery of nꢀbutyl sulfite was an unexpected
finding based on the original notion of using an alcohol to convert the unreacted thionyl chloride
to sulfur dioxide, hydrogen chloride and an alkyl halide. The large excess of alcohol charged to
the quench drove the reaction toward the formation of the alkyl sulfite and hydrogen chloride.
However, the end result is the same since the thionyl chloride is consumed and the aqueous
workup removes any corrosive hydrogen chloride left in the quenched reaction mass, which is
now safe to dispose.
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It should be emphasized that none of the products from the neutralization of thionyl chloride
are harmless. The corrosive hydrogen chloride is easily handled as a dilute aqueous solution and
neutralized with sodium hydroxide, a very common procedure in manufacturing. Any sulfur
dioxide would be handled similarly. The organic products, nꢀbutyl sulfite as well as the low
level nꢀbutyl chloride, are potential alkylating agents. In this case, they are dilute and do not
impact the disposal by combustion of the toluene waste stream. Any personnel exposure to this
waste stream would be very unlikely due to the infrastructure and procedures for handling of
waste streams.
The data indicates that an even larger excess of alcohol should be used to cleanly convert the
thionyl chloride to the corresponding sulfite. In the last case described with enhanced analytical
scrutiny, a 90% excess was adequate to convert the thionyl chloride to sulfite. There was some
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ꢀchlorobutane formed but it was practically at trace levels. Although the quench reaction
should drive off hydrogen chloride overhead to the scrubber system in this approach, the
laboratory data indicated significant acid was still present necessitating an aqueous workup.
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Although this was demonstrated successfully in the laboratory, timing requirements in
production dictated the corrosive waste had to be disposed at a higher than normal cost before
this work was completed.
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Conclusion.
Often too little effort is put forth on issues like this proactively. As documented here, this
particular waste issue was not fully investigated prior to full scale production. This effort
highlighted two key points required to solve the issue of residual reactive compounds like thionyl
chloride in lipophilic organic waste streams. First, there has to be a method to detect the reactive
compound that is adequate to determine the absence or presence of significant amounts of it.
The second is the choice of the chemistry reaction to consume the residual reactive compound.
The important point here is to react it with a convenient lipophilic soluble reagent that does not
create additional problems for the waste stream disposal. The approach of using nꢀbutanol was
shown to be more controllable, reliable, and safer than trying to quench thionyl chloride with
water alone.
Experimental.
All materials were used as received from qualified vendors. Gas chromatography was
performed on an Agilent 7890A with an Agilent J&W, DBꢀ1701, 30M X 0.32mm, 1.00 µm df,
column. Inlet Temperature: 270 °C, Split injection, with a 100:1 split ratio and a septum purge
flow of 3.0 mL/min. Separations were performed at a constant flow of 1.80 mL/min. Gradient
was 40 °C for 1.0 minute, 15 °/min. to 150 °C, no hold time, 20 °/min. to 250 °C, no hold time
for a total run time: 13.33 minutes. FID detector was set at 270 °C. Makeꢀup gas: He with
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constant total flow at 25.0 mL/min. Injection Volume: 1.0 µL. H NMR spectra were obtained
on a Bruker 300 MHz spectrometer in CDCl3.
Aqueous Quench of Thionyl Chloride at Elevated Temperature. Toluene (114.38g) and
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thionyl chloride (7.5 mL, 12 g, 100 mmole) was charged to a jacketed reactor and the
temperature adjusted to 20 °C. Water (13 mL, 722 mmole) was added slowly over 20 minutes;
off gassing was noted during the addition. The reaction was warmed to 82ꢀ91°C for 1.5 hours
and then cooled to 23.8 °C. During the high temperature hold, no visible offꢀgassing was noted.
Sodium hydroxide (50%, 20.31 g, 250 mmole) and water (80 mL) was charged to the addition
funnel; the solution was added to the reaction over 10 minutes with no apparent exotherm.
Agitation was ceased and the lower aqueous layer was removed; pH was 13.12. Water (100 mL)
was added back to the toluene solution and agitated for 5 minutes. The lower aqueous layer was
removed; pH was 1.70.
Aqueous Quench of Thionyl Chloride with Surfactant. Toluene (116.24 g) and thionyl
chloride (7.6 mL, 12.4 g, 104 mmole) was charged into a 500 mL round bottom flask. A
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solution of water (47.35g) and CIP 200 (2.70 g) was charged to an addition funnel and added
slowly to the toluene solution. Cooling was necessary to keep the solution at ambient
temperature. The reaction was stirred at 20ꢀ30 °C for an hour and then heated to reflux (90 °C)
for 24 hours. After the hold time, offꢀgassing was discernible.
Initial Thionyl Chloride Quench with n-Butanol. Toluene (242 mL) and thionyl chloride
(13.5 mL, 22.0 g, 185 mmole) was added to a jacketed reactor. nꢀButanol (22.00 g, 297 mmole)
was added rapidly at 22.7 °C; there was significant offꢀgassing and an exotherm to nearly 27 °C.
The reaction was heated to reflux (110ꢀ112 °C) for an hour and then cooled. Water (100 mL)
was charged and the reaction temperature increased from 25.5 to 27.5 °C with some visible
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smoke formation. Sodium hydroxide (50%, 19.0g, 238 mmole) was added to adjust the pH to
11.78. Agitation was ceased and the lower aqueous layer was removed. The organic layer was
washed twice with 50 mL aliquots of water; pH of the second aqueous layer was 10.15.
Quench of Thionyl Chloride Containing Reaction Mass with n-Butanol. A chlorination
reaction with a 330 mmole input of αꢀhydroxy amine was completed and the combined filtrate of
mother liquor and washes was set aside for neutralization. The total mass of combined filtrate
was 960 g. Toluene is the reaction solvent and wash. The initial charge of thionyl chloride was
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413 mmole.
A 475 g aliquot of the combined filtrate was transferred to a 1 L round bottom glass reactor;
this corresponds to an initial charge of 204 mmoles of thionyl chloride. To an addition funnel
was charged nꢀbutanol (28.8 g, 35.5 mL, 388 mmoles). The nꢀbutanol was added over 15
minutes with no discernible offꢀgassing or selfꢀheating. The reaction was heated to reflux (105
°C) and held for 80 minutes. The heat was removed and the reaction mass was cooled to 15.6
°
C. An aqueous solution of NaOH (15.23 g 50% NaOH and 83.40 g water) was added with
stirring over 5 minutes. The contents were transferred to a separatory funnel and the lower
aqueous phase was removed. The pH of the aqueous cut was 13.36.
The organic layer was removed and the funnel was thoroughly rinsed out with deionized water.
The organic layer was recharged and washed with 100 mL deionized water. The pH of the water
layer was 6.11.
Quench of Thionyl Chloride with n-Butanol; GC/NMR Analysis. Thionyl chloride (24.3 g,
204 mmoles) and toluene (450.8 g) were charged to a 1 L jacketed reactor equipped with
thermocouple, mechanical agitation and reflux capabilities. Temperature was adjusted to 19.8
°
C and nꢀbutanol (28.8 g, 388 mmoles) was charged in a single portion; temperature increased to
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about 24 °C. The reaction temperature was increased to reflux at 111.4 °C and maintained for
110 minutes, followed by cooling to 24.2 °C. An aliquot was removed for analysis.
Deionized water (85 mL) was charged to the reactor and agitated for 45 minutes. Agitation
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was ceased and the pH was measured at 1.45. 50% NaOH (15.22 g, 190 mmoles) was charged
and agitation was resumed. After 20 minutes, agitation was ceased and the pH was measured at
12.9.
Both lower and upper layers were separately removed and the reactor flushed with deionized
water. The upper organic layer was returned to the reactor with deionized water (100 mL) and
thoroughly agitated. The pH of the lower aqueous was measured at 6.81 against a fresh
deionized water blank at 6.72.
Gas chromatographic analysis of the reaction mass prior to the aqueous workup indicated low
levels of 1ꢀchlorobutane and nꢀbutanol. The nꢀbutanol concentration was estimated to be 0.09%
w/w and 1ꢀchlorobutane was no more than 0.005% w/w. The expected concentrations were
2.9% for nꢀbutanol and 3.3% for 1ꢀchlorobutane.
1
H NMR was used to profile the reaction mass. The nꢀbutanol low level was confirmed by
comparison of nꢀbutanol peaks to toluene; 1ꢀchlorobutane was not detectable. However, there
were distinct set of peaks that did not correspond to either analyte. These were determined to be
nꢀbutyl sulfite by comparison to a reference spectrum. The concentration for this compound was
estimated to be 7.6% w/w.
Associated Content.
Gas chromatography chromatograms and NMR spectra for the final butanol quench reaction.
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Acknowledgements.
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I am grateful for the gas chromatography analytical support provided by Senior Analyst Curtis
Barnes and the NMR support by Senior Scientist Dr. Guanmin Wu.
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Author Information.
Corresponding Author
Phone: *641.257.1301.
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Eꢀmail: j.robert.durrwachter@cambrex.com
ORCID
John Durrwachter: 0000-0002-7360-9496
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References
1
Urben, P. G. Bretherick’s Handbook of Reactive Chemical Hazards, Seventh Edition, Volume 1, entry 4090,
‘Sulfinyl chloride; Toluene, Ethanol, Water’, 1482, Elsevier: Amsterdam, 2015.
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Spagnuolo, C.; Wang, S. S. Y. Chem. Eng. News 1992, 70(22). Wang, S. S. Y.; Kiang, S.; Merkl, W. Process
Safety Prog. 1994, 13(3), 153.
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Joshi, M. S., Chem. Eng. News, 1986, 64(14), 2. Jackson, R. W. Chem. Eng. News, 1988, 66(27), 2.
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Grimm, J. S.; Maryanoff, C. A.; Patel, M.; Palmer, D. C.; Sorgi, K. L.; Stefanik, S.; Webster, R. R. H.; Zhang, X.
Org. Process Res. Dev. 2002, 6, 938.
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Brenek, S. J.; am Ende, D. J.; Clifford, P. J. Org. Process Res. Dev. 2000, 4, 585.
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Achmatowicz, M. M.; Thiel, O. R.; Colyer, J. T.; Hu, J.; Elipe, M. V. S.; Tomaskevitch, J.; Tedrow, J. S.; Larsen,
R. D. Org. Process Res. Dev. 2010, 14, 1490.
7
®
®
CIP 100 is a product of Steris Corporation; it is a formulated alkaline cleaner. CIP 200 is a formulated acidic
cleaner from Steris.
8
High Purity Solvent Guide, Burdick and Jackson Laboratories, Inc., 1980.
9
GC quantitation was estimated by comparing analyte peak area responses to the peak areas of a corresponding
external standard and correcting for injection volume, dilution and concentration of the standard.
10
Concentrations of NMR samples were determined by comparing integrated resonances of the analyte relative to
integrated resonances of toluene and assuming the sum of all components integrated in the NMR was 100%. All
integrated areas were corrected for number of protons.
11
Blatt, A.H., Ed., Organic Syntheses, Collective Volume II, 112ꢀ113, 1943.
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