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Explosion Hazards of Sodium Hydride in Dimethyl Sulfoxide,

N,N‑Dimethylformamide, and N,N‑Dimethylacetamide
Qiang Yang,*,† Min Sheng,‡ James J. Henkelis,† Siyu Tu,† Eric Wiensch,† Honglu Zhang,†
Yiqun Zhang,§ Craig Tucker,‡ and David E. Ejeh‡
†
Product Design & Process R&D, Corteva Agriscience, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States
‡
Reactive Chemicals, Corteva Agriscience, Midland, Michigan 48667, United States
§
Analytical Sciences, The Dow Chemical Company, Midland, Michigan 48667, United States
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ABSTRACT: The hazards associated with the thermal decomposition of chemically incompatible sodium hydride solvent
matrices are known, with reports from the 1960s detailing the inherent instability of NaH/dimethyl sulfoxide, NaH/N,N-
dimethylformamide, and NaH/N,N-dimethylacetamide mixtures. However, these hazards remain underappreciated and
undercommunicated, likely as a consequence of the widespread use of these NaH/solvent matrices in synthetic chemistry. We
Downloaded via 94.231.219.180 on August 10, 2019 at 13:26:58 (UTC).

report herein detailed investigations into the thermal stability of these mixtures and studies of the formation of gaseous products
from their thermal decomposition. We expect this contribution to promote awareness of these hazards within the wider
scientific community, encourage scientists to identify and pursue safer alternatives, and most importantly, help to prevent
incidents associated with these reactive mixtures.
KEYWORDS: sodium hydride (NaH), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF),
N,N-dimethylacetamide (DMAc), thermal instability, explosion

■ INTRODUCTION
The use of NaH as a strong base is commonplace in synthetic
organic chemistry.1 Generally speaking, NaH is easy to handle
and store and often offers predictable reactivity and high atom
efficiency. As a result, it has been used to facilitate a wide range
of chemical transformations.2 The most commonly used
solvents for reactions that use NaH are dimethyl sulfoxide
(DMSO), N,N-dimethylformamide (DMF), and N,N-dime-
thylacetamide (DMAc) because of their complementary
physical properties and their ability to solubilize both organic
and inorganic compounds.
The hazards associated with the thermal instability of NaH/
DMSO, NaH/DMF, and NaH/DMAc mixtures have been a
growing concern within the chemistry community.3 In addition
to the desirable physical properties of DMSO to solubilize
both organic and inorganic compounds, dimsyl ion (also
known as sodium dimsylate or methyl sulfinyl carbanion),
prepared via the reaction of NaH with DMSO under nitrogen
at 70−75 °C, has found wide applications in a variety of
chemical transformations since the seminal publication by
Corey and Chaykovsky in the early 1960s.4 The thermal
instability of dimsyl ion was first highlighted by Corey and
Chaykovsky in 19654b and further studied by many research
groups.5 The first reported explosion resulting from a NaH/
DMSO mixture was in 1966,6 when scientists at the Cancer
Chemotherapy Research Department of Mount Zion Hospital
and Medical Center (Palo Alto, CA) were scaling up a
methylation reaction that employed NaH in DMSO, following
a method reported by Russell and Weiner.7 The scientists
noted incomplete conversion when the reaction was carried
out using a NaH/DMSO molar ratio of 0.19:1 and thus
increased the ratio to 0.24:1. The reaction mixture was
maintained at 70 °C for 1 h and then cooled, during which
time they observed a sharp temperature spike followed by an
explosion that was accompanied by a noxious gas. Immediately
after the disclosure of this incident, an analogous explosion
from a NaH/DMSO mixture was reported,8 albeit at a lower
temperature (50 °C) and concentration (0.17:1 NaH/DMSO
on a molar basis) compared with the conditions employed in
the earlier incident.6
The thermal decomposition of a NaH/DMF mixture was
first observed in the early 1960s, first by Powers et al., who
noted energetic decomposition during a NaH-mediated
cleavage of a formyl group,9 and Brimacombe et al. during
the alkylation of a carbohydrate using NaH as the base.10
Nasipuri et al. later reported the aromatization of various
cyclohexenones using NaH in DMF, in which the authors
acknowledged the decomposition of DMF in the presence of
NaH but still carried out their reactions at 100 °C.11 The
researchers proposed that the active base in these reactions was
sodium dimethylamine, resulting from the reaction of DMF
with NaH.
The hazards associated with the thermal instability of NaH/
DMF pose an even greater risk as the reaction scale increases.
Reports of large-scale incidents associated with the thermal
instability of NaH/DMF were noted in the early 1980s. In the
first reported example, conducted on a pilot-plant scale at
SmithKline Beckman, a condensation reaction employing NaH
in DMF experienced uncontrolled self-heating on 2500 L scale
that resulted in the failure of a reactor’s rupture disk.12
Special Issue: Corteva Agriscience
Received: June 18, 2019

© XXXX American Chemical Society A DOI: 10.1021/acs.oprd.9b00276

Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

Through a series of calorimetric studies, the research team

observed that mixtures of NaH with either DMF or DMAc
would begin to self-heat at temperatures as low as 26 °C and
that the temperature would rapidly increase to 80 °C, at which
point the cooling capacity of the pilot-plant reactor would be
exceeded. They further commented that the onset temperature
of decomposition was between 40 and 50 °C with carefully
dried DMF; however, the detailed thermal stability data
resulting from the study were not reported. A second account
was reported by Burdick and Jackson Laboratories in the same
year, stating that uncontrolled heating of a NaH/DMF reaction
mixture began at 40 °C and that the reaction temperature
quickly rose to more than 100 °C in less than 10 min.13
Although full cooling was applied to the reaction vessel, the
temperature could not be controlled, and the majority of the
DMF solvent evaporated before the reaction subsided. They Figure 1. Numbers of publications using NaH/DMSO, NaH/DMF,
commented that the reaction had been conducted many times and NaH/DMAc in Organic Letters in 2014−2018.
without an incident, which highlights the unpredictable nature
of this chemistry. While they suspected the reactor’s material of
construction (stainless steel) to be the likely cause of the
decomposition, this hypothesis was proven invalid by later
studies and data presented in this contribution.
The safety concerns regarding the thermal instability of NaH
mixtures were reiterated in two editorials by the previous
Organic Process Research & Development Editor-in-Chief,
Trevor Laird,14 who commented that multiple runaway
reactions with NaH/DMF mixtures had occurred before the
first report was published in 1982. These editorials drew much-
needed attention to NaH-containing reactive mixtures and
highlighted the importance of scientific communication to
raise awareness of these hazards and alert others to such
dangers.
Despite the numerous reports intended to caution scientists,
the hazards associated with NaH/DMSO, NaH/DMF, and
NaH/DMAc reactive mixtures remain underappreciated and Figure 2. Numbers of publications using NaH/DMSO, NaH/DMF,
and NaH/DMAc in The Journal of Organic Chemistry in 2014−2018.
inadequately discussed, overshadowed by the sheer number of
publications that utilize these hazardous conditions, further
diminishing their impact upon the chemistry community. As
shown in Figures 1−3, the number of publications reporting
the use of these hazardous conditions each year remains
consistently high. Between 2014 and 2018, Organic Letters
published 38−62 examples/year (Figure 1), whereas The
Journal of Organic Chemistry (Figure 2) and the Journal of
Medicinal Chemistry (Figure 3) published 28−46 and 67−94
examples/year, respectively.
It should be noted that most of the papers published in
Organic Process Research & Development employing NaH/
DMSO, NaH/DMF, and NaH/DMAc only reported these
hazardous conditions in their original discovery-phase routes
(Figure 4). In most instances, the authors acknowledged the
inherent safety hazards associated with these reactive mixtures
and designed their processes away from these mixtures in the
final routes. For example, Dahl et al.15 employed sodium Figure 3. Numbers of publications using NaH/DMSO, NaH/DMF,
dimsylate as the base in their process for the synthesis of (S)-2- and NaH/DMAc in the Journal of Medicinal Chemistry in 2014−2018.
({3-[(S)-5-chloro-1-(4-chlorophenyl)indan-1-yl]propyl}-
methylamino)propionic acid. The researchers performed a
detailed reaction calorimetry evaluation, which indicated that developed a safer process in which the reaction was performed
the sodium dimsylate decomposed at temperatures as low as using 4 equiv of DMSO (relative to NaH) in 7 volumes of
∼50 °C with an adiabatic temperature rise (ΔTad) of 500 °C in THF (relative to DMSO) and successfully scaled up this
pure DMSO. In contrast, when the DMSO solution of sodium process to 4.1 kg of 60 wt % NaH in mineral oil. Nonetheless,
dimsylate was diluted with THF, the lowest observed there are examples where these hazardous mixtures were
decomposition temperature was ∼100 °C with a ΔTad of employed in the final reaction conditions, one of which
230 °C. On the basis of these results, the researchers includes a large-scale production that operated using 880 mol
B DOI: 10.1021/acs.oprd.9b00276
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development
Figure 4. Numbers of publications using NaH/DMSO, NaH/DMF,
and NaH/DMAc in Organic Process Research & Development in 1997−
2018.
of NaH (35.2 kg of 60 wt % NaH in mineral oil).16 In these
cases the authors restated that alternative reaction conditions
were not appropriate and that all of the reactions were
conducted within safe operating ranges and in a reactor made
of compatible materials of construction.8 It is worth noting that
calorimetry studies have proven that these hazards are
independent of the reactor material of construction (stainless
steel). Furthermore, critical reaction parameters, such as
residual water, reaction temperature, and relative concentration
of NaH, might help mitigate some of the hazards associated
with their use, but they do not completely address the dangers
of spontaneous thermal decomposition.
This literature survey shows that reactions with these
matrices continue to appear in publications, indicating their
relatively common use and suggesting that the safety hazards
associated with the thermal instability of NaH/DMSO, NaH/
DMF, and NaH/DMAc mixtures remain underappreciated. In
this contribution, we communicate the results of detailed
thermal stability evaluations of these hazardous combinations
in order to promote awareness of these hazards within the
chemistry community and encourage scientists to employ safer
reaction conditions, with the ultimate goal of preventing
incidents relating to these hazards.
Figure 5. ARC heat rate and pressure vs temperature profiles of a NaH/DMSO mixture.
C DOI: 10.1021/acs.oprd.9b00276
■
Article
RESULTS AND DISCUSSION
An exothermic reaction is typically maintained at the optimal
temperature by applying external cooling until reaction
completion and then cooled for workup and isolation of the
product. However, in cases of insufficient cooling or cooling
failure, unreacted components will further react to release
energy, leading to a higher reaction temperature. In a worst-
case scenario (e.g., all reactants are accumulated and the
reaction continues under adiabatic conditions), the reaction
temperature would reach the maximum temperature of a
synthesis reaction (MTSR), which is equal to the desired
reaction temperature plus ΔTad.17 In cases when the MTSR
exceeds the onset temperature of reaction mixture decom-
position, a secondary reaction would be initiated, potentially
leading to runaway scenarios. It is thus crucial to evaluate
reaction calorimetry and thermal stability hazards of chemical
reactions and to design control strategies accordingly in order
to ensure that thermal decomposition of the reaction mixture is
not triggered. Measurements of the heat of the desired reaction
and ΔTad are generally performed using an instrument such as
an RC1 reaction calorimeter, a micro reaction calorimeter
(μRC), or an EasyMax HF Cal heat flow calorimeter. The
thermal stability of reaction mixtures is generally characterized
with a differential scanning calorimetry (DSC), a thermal
screening unit (Tsu), an accelerating rate calorimetry (ARC),
and/or a vent-sizing package (VSP).
1. Thermal Stability Evaluation of NaH/DMSO. ARC
analysis of 4.55 g of a mixture of 9.7% NaH, 6.4% mineral oil,
and 83.9% DMSO18 recorded two small exothermic events
followed by a significant exothermic event with an onset
temperature of 56.8 °C (Figure 5 and Table 1). This exotherm
caused the rupture of an ARC cell designed with an average
burst pressure of 14 500 psi (Figure 6, left). The force
generated from this explosion was strong enough to displace
the reactor housing, which sat on top of the ARC reactor
(Figure 6, right). The full heat and pressure information on
these exothermic events could not be recorded because of this
rupture.
A mixture of 10.3% NaH, 6.9% mineral oil, and 82.8%
DMSO was then studied by DSC to better understand the
total heat output that could result from an exothermic event
strong enough to rupture an ARC cell. As shown in Figure 7,
DSC analysis recorded an endothermic event (14 to 39 °C), a
minor exothermic event (39 to 120 °C), and two consecutive
major exothermic events (120 to 285 °C). The first major
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

Table 1. ARC Analysis of a NaH/DMSO Mixture

sample description 9.7% NaH + 6.4% mineral oil + 83.9%
DMSO
total sample mass (g) 4.5471
Cp of sample (J g−1 °C−1) 1.923
ARC cell mass (g) 21.9702
set end temperature (°C) 350
phi 2.06
onset temperature (°C) 56.8
peak temperature (°C) −
end temperature (°C) −
max self-heating rate −
(°C/min)
total heat (J/g) ruptured Figure 8. ARC temperature and pressure vs time profiles of a NaH/
DMSO mixture.

overlaid in red (air blank) and black (sample of interest), are

compared in Figure 9. The gases detected in the sample

Figure 6. Pictures of (left) a ruptured Hastelloy C ARC cell and

(right) the displaced ARC reactor housing resulting from the cell
explosion.

Figure 9. Headspace GC/MS analysis of the gaseous products from

the thermal decomposition of a NaH/DMSO mixture.

referenced against the NIST chemical library supported the

Figure 7. DSC analysis of a NaH/DMSO mixture.
exothermic event had a peak temperature of 146 °C and a total
heat of −413.5 J/g, while the second major exothermic event
had a peak at 255 °C and a total heat of −810.2 J/g. With the
combined heat of these two events (−1123.7 J/g), this mixture
was considered to be explosive according to the Yoshida
correlation.19 As a direct comparison, pure DMSO decom-
poses at around 278 °C with a heat output of −911.59 J/g by
DSC analysis.
While the first of the two small exothermic events recorded
by ARC (21.3 to 26.4 °C, EXO1 in Figure 8) was attributed to
the heat of mixing, the second one (36.9 to 43.5 °C, EXO2 in
Figure 8), with a total heat of only −93.2 J/g, was most likely
caused by the reaction between NaH and DMSO. Surprisingly,
this minor exotherm generated a significant amount of
noncondensable gases that raised the cell pressure from 129
to 1289 psi between the end of the first exothermic event (109
min) and the start of the major exothermic event (635 min,
EXO3 in Figure 8).
Analysis of the gaseous products from EXO2 was performed
using headspace GC/MS. The total ion chromatograms (TIC),
D DOI: 10.1021/acs.oprd.9b00276
presence of ethylene and dimethyl sulfide as the decomposition
products,20 along with DMSO.21 Undoubtedly, the generation
of large volumes of gases poses a significant safety concern and
contributed to the explosion during the dominant exothermic
event.
2. Thermal Stability Evaluation of NaH/DMF. The
thermal stability of NaH/DMF mixtures was evaluated by ARC
analysis. As shown in Figure 10, a significant exothermic
decomposition with an onset temperature of 76.1 °C was
detected with a mixture of 9.5% NaH, 6.3% mineral oil, and
84.2% DMF. This decomposition produced an exotherm of
−528.4 J/g with a maximum self-heating rate of 7.23 °C/min.
Increasing the weight ratio of NaH to 24.6% (in 16.4% mineral
oil and 59% DMF) significantly lowered the decomposition
onset temperature to 39.8 °C and increased the peak self-
heating rate to 634.7 °C/min, affording a total exotherm of
greater than −601.8 J/g (Table 2). Both tests had substantial
cool-down pressures, confirming that the decomposition of
DMF resulted in the formation of significant amounts of
gaseous products.
Identification of the gaseous products resulting from the
thermal decomposition of NaH/DMF was performed using
evolved gas analysis (EGA) Micro-GC analysis. In a control
experiment with NaH in mineral oil, only the residual water in
the EGA Micro-GC system, transfer lines, and sample cup was
detected at <100 °C. Release of H2 gas was detected when the
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

Figure 10. ARC heat rate and pressure vs temperature profiles of NaH/DMF mixtures.

Table 2. ARC Analysis of NaH/DMF Mixtures

sample description 9.5% NaH + 6.3% mineral oil + 84.2% DMF 24.6% NaH + 16.4% mineral oil + 59% DMF
total sample mass (g) 4.1234 3.3896
Cp of sample (J g−1 °C−1) 2.010 1.930
ARC cell mass (g) 21.8926 14.8079
set end temperature (°C) 350 200
phi 2.11 1.95
onset temperature (°C) 76.1 39.8
peak temperature (°C) 133.8 126.2
end temperature (°C) 200.7 >199.7
max self-heating rate (°C/min) 7.23 634.7
total heat output (J/g) −528.4 >−601.8

temperature reached ∼165 °C and ended at ∼360 °C,

indicating that the formation of H2 was caused by the thermal
decomposition of NaH rather than hydrolysis by residual water
(Figure 11).

Figure 12. Gaseous products (EGA Micro-GC) from the thermal

decomposition of NaH/DMF.

3. Thermal Stability Evaluation of NaH/DMAc. Similar

Figure 11. Thermogram of NaH in mineral oil by EGA Micro-GC.
The profiles of the gaseous products resulting from the
thermal decomposition of the NaH/DMF mixture are shown
in Figure 12. Water was detected when the temperature was
below 140 °C and was likely the result of residual water in the
EGA Micro-GC system, transfer lines, and sample cup. Two
separate peaks were detected for H2, the first at 140−270 °C
and the second at 270−360 °C. In addition to H2, carbon
monoxide (CO), methane (CH4), and ethylene or acetylene
were also observed within the same temperature range as the
first H2 peak. A trace amount of carbon dioxide (CO2) was
also found at >300 °C.22 The formation of these gaseous
products suggests that a more complicated, potentially radical
decomposition mechanism occurs during the thermal decom-
position of NaH/DMF.
E DOI: 10.1021/acs.oprd.9b00276
to the thermal decomposition of NaH/DMF, ARC analysis of
a mixture of 9% NaH, 6% mineral oil, and 85% DMAc
evidenced a decomposition onset temperature of 56.4 °C with
a peak self-heating rate of 5.78 °C/min and a total heat release
of −422.6 J/g. Increasing the content of NaH to 16.2%
significantly lowered the decomposition onset temperature to
30.1 °C and substantially increased the maximum self-heating
rate to 479.1 °C/min with a total heat output of −528.2 J/g
(Figure 13 and Table 3). Again, both experiments resulted in
significantly high cool-down pressures, confirming the
formation of noncondensable gaseous products from the
thermal decomposition. These results confirm that the thermal
decomposition of the NaH/DMAc combination could also
result in runway scenarios.
EGA Micro-GC analysis of the NaH/DMAc reaction
mixture showed that the release of H2 occurred at a lower
temperature (<110 °C) than with the NaH/DMF sample, with
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

Figure 13. ARC heat rate and pressure vs temperature profiles of NaH/DMAc mixtures.

Table 3. ARC Analysis of NaH/DMAc Mixtures

sample description 9% NaH + 6% mineral oil + 85% DMAc 16.2% NaH + 10.8% mineral oil + 73.1% DMAc
total sample mass (g) 4.2240 5.3631
Cp of sample (J g−1 °C−1) 1.975 1.943
ARC cell mass (g) 22.0010 14.7578
set end temperature (°C) 350 200
phi 2.11 1.60
onset temperature (°C) 56.4 30.1
peak temperature (°C) 123.0 122.7
end temperature (°C) 157.8 200
max self-heating rate (°C/min) 5.78 479.1
total heat (J/g) −422.6 −528.2

the majority of H2 generation occurring in the temperature
range of 104−305 °C. Other noncondensable gaseous
products, such as CH4, ethane, ethylene or acetylene, and
CO, were also observed in this temperature range as well as
above 300 °C (Figure 14).22
explosion during the ARC analysis that was forceful enough to
displace the ARC housing. We expect this report to promote
awareness of these hazards in the chemistry community,
encouraging scientists to employ safer alternative conditions
(e.g., alternative bases, NaH with stable solvents, etc.)23 and
avoid incidents related to these hazards.

Figure 14. Gaseous products (EGA Micro-GC) from the thermal
decomposition of NaH/DMAc.
■ EXPERIMENTAL SECTION
General. All reagents were commercially available and used
as purchased without further purification.
Procedure for ARC Analysis. An accelerating rate
calorimeter manufactured by Thermal Hazard Technology
was used in this study. A preweighted NaH/mineral oil sample
was loaded into a Hastelloy C ARC cell. The ARC sphere was
connected to the calorimeter lid and purged with N2. The ARC
test was started and put in EXO mode, and then the reaction
solvent was manually injected with a syringe. The ARC
experiment was performed in heat−wait−search (HWS)
mode. A heat step of 5 °C, waiting time of 30 min, and
detection threshold of 0.02 °C/min were utilized for each

■ CONCLUSIONS
The inherent thermal instability hazards of NaH/DMSO,
NaH/DMF, and NaH/DMAc mixtures have been well-
documented in the literature over the past few decades, yet
the dangers remain underappreciated and poorly communi-
cated, as evidenced by their continued appearance in hundreds
of publications. The data outlined in this contribution confirm
that these reactive mixtures undergo exothermic decomposi-
tion at relatively low temperatures, occurring concurrently with
the generation of noncondensable gases. The dangers
associated with NaH/DMSO mixtures were evidenced by an
F DOI: 10.1021/acs.oprd.9b00276
sample.
Procedure for DSC Analysis. A Q2500 differential
scanning calorimeter from TA Instruments was used for the
constant-heating-rate tests (at 10 °C/min) in this study. A
3.2515 mg sample (a mixture of 10.3% NaH, 6.9% mineral oil,
and 82.8% DMSO) was sealed within a gold-plated high-
pressure crucible with N2 in the headspace. The sealed crucible
had a total internal volume of ∼20 μL and was able to
withstand pressures of up to 3000 psi at 400 °C, preventing the
release of any reaction materials, products, or byproducts. The
DSC analysis of pure DMSO was performed following the
same method in a sealed glass capillary tube under N2.24
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

Procedure for EGA Micro-GC Analysis. A Varian model
CP-490 Micro-GC system was used for EGA of the NaH/
solvent mixtures using a Frontier Py2020iD pyrolysis unit
(Figure 15). Approximately 2 mg of NaH (60% dispersion in
Figure 15. Flow diagram of the EGA Micro-GC system.
mineral oil) was added with 15 μL of solvent (DMF or
DMAc). The sample was analyzed by EGA Micro-GC using
helium as the purge gas through the pyrolysis oven. The ramp
rate of the pyrolysis oven was 5 °C/min, and the samples were
heated from 40 to 400 °C. The Micro-GC system was used to
analyze the gases evolved after the sample was inserted into the
pyrolysis oven and the programmed heating cycle was started.
An aliquot of the pyrolysis effluent was injected into the Micro
GC system every 150 s. The helium flow rate was
approximately 13 mL/min.
A Molsieve 5A (MS5A) module with argon as the carrier gas
was used to separate H2. An MS5A module with helium as the
carrier gas was used to separate CO and CH4. A PoraPLOT Q
(PPQ) module with helium as the carrier gas was used to
separate CO2, CH4, water, ethane, and ethylene/acetylene. A
19CB module with helium as the carrier gas was used to
separate DMF and DMAc. Quantitation was performed using a
microthermal conductivity detector (TCD). H2, N2, CO, CO2,
CH4, ethane, propane, and butane responses were calibrated
against certified gas standard mixtures (Matheson Tri-Gas).
H2O responses were identified and estimated on the basis of
literature references.25
Varian CP-490 Quad-Channel Micro-GC Specifications.
Serial no. (SN): GC0912B639. Channel 1: 20 m MS5A
module with backflush, SN 61685, part no. (PN) 494001370.
Channel 2: 10 m MS5A module with backflush, SN 61162, PN
494001360. Channel 3: 10 m PPQ module with backflush, SN
61222, PN 494001430. Channel 4: 6 m 19CB module, SN
61607, PN 492004810. Dell Latitude Laptop PC with Agilent
EZChrom Elite software, version 3.2.2 SP2.
Method Settings. Sample time: 40 s. Sample line temper-
ature: 100 °C. Stabilizing time: 5 s. Continuous flow: disabled.
Number of flush cycles: 1. Peak simulation: disabled. The
channel settings are shown in Table 4.
Procedure for Headspace GC/MS Analysis. The sample
was preheated at 40 °C for 1 h in a headspace vial and analyzed
along with an empty headspace vial, which served as the blank.
An Agilent 5975C inert XL GC/MSD system with triple-axis
detector was used. The instrument was equipped with both
direct liquid, SPME, and headspace capabilities. A Supelco Q-
PLOT capillary column with dimensions of 30 m × 0.32 mm
(cat. no. 24242) was used for the analysis. The agitation
temperature of the sample compartment was set at 40 °C. The
NIST chemical library was used for the identification of
gaseous products.
■ AUTHOR INFORMATION
Corresponding Author
*E-mail: qiang.yang@corteva.com.
ORCID
Qiang Yang: 0000-0003-3762-5015
Siyu Tu: 0000-0002-6126-5729
Author Contributions
The manuscript was written through contributions of all
authors. All of the authors approved the final version of the
manuscript.
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
The authors thank Dr. Gregory T. Whiteker for his
constructive suggestions during the preparation of this
manuscript.
■ REFERENCES
(1) Hansley, V. L.; Carlisle, P. J. The Production of Sodium Hydride
and Some of its Reactions. Chem. Eng. News 1945, 23 (15), 1332−
1380.

Table 4. Micro-GC Channel Settings

channel 1 channel 2 channel 3 channel 4

module 20 m MS5A 10 m MS5A 10 m PPQ 6 m 19CB
carrier gas argon helium helium helium
column temp. (°C) 146 90 73 80
injection temp. (°C) 100 100 100 100
injection time (ms) 50 50 50 50
backflush time (s) 10 10 20 NA
detector on on on on
TCD temp. limit check on on on on
sensitivity auto auto auto auto
pressure mode static static static static
initial pressure (psi) 30 30 16 18
sampling frequency (Hz) 100 100 100 100
run time (s) 150 150 150 150
acquisition delay (s) 0 0 0 0

G DOI: 10.1021/acs.oprd.9b00276
Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development Article

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Sons, 1995; Vol. 7, pp 4568−4571. Displacement. Org. Process Res. Dev. 2011, 15, 1442. (c) Yang, Q.; Li,
(3) (a) Bretherick, L. Dimethyl sulfoxide: Sodium hydride. In X.; Lorsbach, B. A.; Muhuhi, J. M.; Roth, G. A.; Gray, K.; Podhorez,
Bretherick’s Handbook of Reactive Chemical Hazards, 3rd ed.; D. E. Development of a Scalable Process for the Insecticidal
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H DOI: 10.1021/acs.oprd.9b00276
Org. Process Res. Dev. XXXX, XXX, XXX−XXX