Degradation of Organic Cations under Alkaline Conditions

Article abstract of DOI:10.1021/acs.joc.0c02051

Understanding the degradation mechanisms of organic cations under basic conditions is extremely important for the development of durable alkaline energy conversion devices. Cations are key functional groups in alkaline anion exchange membranes (AAEMs), and AAEMs are critical components to conduct hydroxide anions in alkaline fuel cells. Previously, we have established a standard protocol to evaluate cation alkaline stability within KOH/CD3OH solution at 80 °C. Herein, we are using the protocol to compare 26 model compounds, including benzylammonium, tetraalkylammonium, spirocyclicammonium, imidazolium, benzimidazolium, triazolium, pyridinium, guanidinium, and phosphonium cations. The goal is not only to evaluate their degradation rate, but also to identify their degradation pathways and lead to the advancement of cations with improved alkaline stabilities.

Full text of DOI:10.1021/acs.joc.0c02051

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Degradation of Organic Cations under Alkaline Conditions
Wei You,§ Kristina M. Hugar,§ Ryan C. Selhorst, Megan Treichel, Cheyenne R. Peltier,
Kevin J. T. Noonan,* and Geoffrey W. Coates*
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ABSTRACT: Understanding the degradation mechanisms of organic cations
under basic conditions is extremely important for the development of durable
alkaline energy conversion devices. Cations are key functional groups in alkaline
anion exchange membranes (AAEMs), and AAEMs are critical components to
conduct hydroxide anions in alkaline fuel cells. Previously, we have established a
standard protocol to evaluate cation alkaline stability within KOH/CD3OH
solution at 80 °C. Herein, we are using the protocol to compare 26 model
compounds, including benzylammonium, tetraalkylammonium, spirocyclicammo-
nium, imidazolium, benzimidazolium, triazolium, pyridinium, guanidinium, and
phosphonium cations. The goal is not only to evaluate their degradation rate, but
also to identify their degradation pathways and lead to the advancement of cations
with improved alkaline stabilities.
Scheme 1. General Illustration of Cation Degradation
Pathways under Alkaline Conditions
INTRODUCTION
■
During our long-term effort to develop durable alkaline anion
exchange membranes (AAEMs), one of our major concerns is
the alkaline stability of cationic functional groups in AAEMs.1
The function of AAEMs is to transport hydroxide anions
within clean energy conversion devices such as anion exchange
membrane fuel cells (AEMFCs), alkaline water electrolyzers,
electrodialyzers, and redox flow batteries.2−4 Organic cations
are key components in AAEMs as they serve as counterions of
hydroxide anions and are covalently attached to polymeric
backbones in AAEMs. However, as cations are vulnerable to
strong nucleophiles and bases such as hydroxide, their alkaline
stability is directly related to the life span of AAEMs.5 Organic
cations are common synthesis intermediates, and the reactions
between them and bases have been well documented,
including nucleophilic substitution (SN2), Hofmann elimina-
tion (E2), ylide formation, Sommelet−Hauser rearrangement,
and Stevens rearrangement.6−8 Nevertheless, the cations in
AAEMs need to remain intact for thousands of hours under
high temperature (>80 °C) and high pH (>14) conditions.
Hence, understanding cation degradation under alkaline
conditions is key to designing better cationic candidates for
AAEM applications. Some common degradation pathways are
shown in Scheme 1. In general, all organic cations can undergo
SN2 at the α-position, and E2 can occur when β-hydrogens are
present.9 N-conjugated cations can also be attacked through
nucleophilic addition to the CN bonds.8 Additionally, when
oxygen-based nucleophiles react with phosphonium cations,
Cahours−Hofmann reaction may occur to form phosphine
oxide.10
AAEM systems, so that their degradation products, kinetics,
and mechanisms can be unambiguously assigned using nuclear
magnetic resonance (NMR) and high-resolution mass
spectrometry (HRMS) techniques.9−24 Although significant
progress has been achieved over the past decade in enhancing
the understanding of the cation alkaline stability, two major
limitations still exist: inconsistent testing conditions and a lack
of comparison among different classes of cations. It is broadly
accepted that the cation stability studies need to be performed
with concentrated base at high temperatures, although the
choice of solvents differs. The reported solvent systems include
water,9,11−13 methanol,14−18 anhydrous DMSO,19,20 water/
Received: August 25, 2020
Model compound study is a common strategy to
deconvolute cation decomposition in complicated polymeric
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methanol cosolvent,21−23 water/DMSO cosolvent,24 and
water/chlorobenzene phase transfer conditions.10 One of the
most comprehensive cation stability studies led by Marino and
Kreuer tested a series of N-based cations in 6 M KOH aqueous
solution at 160 °C,9 and this report has pioneered a number of
follow-up studies on piperidinium-functionalized AAEMs.25−28
However, cation degradation in aqueous solution is relatively
slow, and it is difficult to represent the low-hydration-level fuel
cell operating conditions. As a result, organic solvents have
been applied to lower the hydration levels of cations and
accelerate their degradation. In our recent viewpoint, we
discussed several important aspects to establishing a standard
stability-evaluation protocol.15 One of our characteristic
conditions is the use of methanol-d3 (CD3OH) as the solvent,
and its major advantages include the following: (1) good
solvation of cations, (2) a potential fuel of AEMFCs, (3)
accelerated degradation conditions in the presence of
methoxide anions, (4) capability of avoiding H/D exchange,
and (5) locking signals for H NMR analysis. Herein, 26
cations are divided into six groups (i.e. benzylammonium,
tetraalkylammonium, spirocyclicammonium, imidazolium,
other N-conjugated cations, and phosphonium) and are
evaluated using our standard protocol (Chart 1). We are
reporting on the detailed degradation rates and pathways for
individual cations in KOH/CD3OH at 80 °C to facilitate direct
comparison of these different species.
assign the decomposition products and the dominating
degradation pathways. The results of the kinetics of all the
tested cations are shown in Figure 1 (1 M conditions) and
Figure 2 (2 M conditions). As a side note, we have previously
reported the stability studies of some of the cations under
KOH/CD3OH conditions,10,14,29 while herein we are using the
data to provide a systematic comparison and discussion.
Additionally, control experiments have also been performed to
confirm that the internal standard NaDSS is sufficiently stable
under alkaline conditions (Figure S74).
Benzylammonium cations (Scheme 2) have been the focus
of study in AAEMs over the past two decades. Cations such as
BTMA (2) are not only straightforward to incorporate in
AAEMs, but also lack β-hydrogens and therefore cannot
degrade through Hofmann elimination. However, numerous
reports have pointed out that these benzylammonium cations
are not stable under alkaline conditions.9,11,12,29,30 Five
benzylammonium model compounds (1−5) were evaluated
using our protocol, and the results are shown in Scheme 2
(also see Figures 1A and 2A). BTMA (2) degraded via an SN2
mechanism, and a nucleophilic attack at the benzylic position
was more favored than at the methyl position to produce ether
and tertiary amine products.14 When cyclohexyl groups were
applied to derivatize BTMA into N-benzyl-N-cyclohexyl-N-
methylcyclohexanaminium (5), we observed less than 1%
cation remaining after five days (Scheme 2). This result
contrasts with a previous report by Bae and Mohanty,11
wherein cyclohexyl substituents improved cation stability in
water. This is possibly because the cation with more
hydrophobic substituents is better solubilized in methanol,
and the strong steric interference in 5 also increases its ground
state energy.31 Using our protocol, only benzyl methyl ether
15
1
Chart 1. Cations explored in this study. The six groups
represent some of the most common cations in AAEMs.
1
and N,N-dicyclohexylmethylamine were detected by H NMR
spectroscopy after the stability study. N-Benzylmorpholinium
(4), which contains an ether functional group, has been
hypothesized to have increased conductivity and alkaline
stability due to its expanded hydration sphere surrounding the
organic cations.32 However, 4 degraded completely over 20
days under 1 M KOH/CD3OH conditions, mostly through
benzylic SN2 attack to produce N-methylmorpholine and
benzyl methyl ether (Scheme 2). Notably, a small amount of
vinyl ether degradation product was also detected. This is likely
because the adjacent oxygen atom increases the acidity of the
β-hydrogens in morpholinium, resulting in a higher relative
rate of Hofmann elimination.33 Bicyclic ammonium cations
derivatized from DABCO (1,4-diazabicyclo[2.2.2]octane) are
also common motifs in AAEMs,34 while faster degradation of
N-benzyl DABCO (3) than BTMA was observed under our
KOH/methanol conditions (Scheme 2). Both the benzylic and
the ring-opening SN2 attack were identified through the
analysis of the 1H NMR spectrum, and the latter pathway was
favored in a 2:1 ratio likely due to the release of ring strain.
HRMS was applied to further identify the proposed CD3O−
ring-opened product, as methanol-d3 was used as the reaction
media (Figure S17). N-Benzylquinuclidinium (1) is a similar
bicyclic ammonium cation as N-benzyl DABCO that has been
applied in AAEMs,35 but has a methine at the bridgehead in
place of a nitrogen atom. This substitution resulted in
significantly improved alkaline stability, with 67% of the
original cation remaining after 1 M KOH/CD3OH for 30 days
(Scheme 2). Similar to 3, the degradation pathways yielded the
ring-opened products, benzyl methyl ether and quinuclidine.
The ring-opening reaction was slightly preferred (ca. 1.3:1)
RESULTS AND DISCUSSION
■
With the previously established alkaline stability protocols,15
the organic cations were subjected to 1 M or 2 M KOH/
CD3OH solution at 80 °C for 30 days with an internal
standard (3-(trimethylsilyl)-1-propanesulfonic acid sodium
salt, NaDSS) in sealed NMR tubes. The decomposition
1
processes were frequently monitored by H NMR analysis to
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Figure 1. Alkaline stability results for cations 1−26 under 1 M KOH/CD3OH conditions.
Figure 2. Alkaline stability results for cations 1−26 under 2 M KOH/CD3OH conditions.
and the isotope labeled product was also observed by HRMS
(Figure S11).
Hofmann elimination (Scheme 3). The major degradation
pathway of 8 was nucleophilic demethylation, and only 1%
Hofmann elimination was detected (Scheme 3).40
A
Because benzyl SN2 degradation is a major issue for
benzylammonium cations, some recent reports have demon-
strated that ammonium cations without benzyl substituents,
such as tetraalkylammonium cations, have better alkaline
stability, although β-hydrogen atoms are present in these
cations.9,36−39 We tested four different tetraalkylammonium
model cations (6−9) using the standard protocol (Scheme 3
and Figures 1B and 2B). Both tetrabutylammonium (7) and
tetradecyltrimethylammonium (8) have significantly enhanced
alkaline stability (96 and 94% cation remaining, respectively).
The 4% observed degradation products of 7 came from
comparison of 8 with BTMA (2) clearly shows the
improvement of alkaline stability achieved by replacing the
benzyl substituent with a long alkyl chain. These observations
suggest that Hofmann elimination in alkylammonium cations is
much slower than nucleophilic substitution of benzyl and
methyl groups under alkaline conditions. Cyclic ammonium
cations are proposed to have even better alkaline stability than
long alkyl chains because Hofmann elimination can be
conformationally disfavored.9,25−28 As follows, piperidinium
cation (6) showed 97% cation remaining after 1 M KOH/
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as volatile compounds such as ethylene, dimethyl ether, and
trimethylamine can be easily detected in the sealed NMR
tubes.
It is proposed that spirocyclic piperidinium cations have
even better alkaline stability than simple piperidinium,9,41,42
and thus we also tested spirocyclic cations (Scheme 4 and
Scheme 2. Stability Results of Benzylammonium Cations
(1−5) Under 1 M and 2 M KOH/CD3OH 80 °C
Conditions. Numbers in Parentheses Indicate 2 M KOH/
CD3OH
Scheme 4. Stability Results of Spirocyclic Ammonium
Cations (10−14) Under 1 M and 2 M KOH/CD3OH 80 °C
Conditions. Numbers in Parentheses Indicate 2 M KOH/
CD3OH
a
b
20 days. 5 days.
Scheme 3. Stability Results of Tetraalkylammonium Cations
(6−9) Under 1 M and 2 M KOH/CD3OH 80 °C
Conditions. Numbers in Parentheses Indicate 2 M KOH/
CD3OH
Figures 1C and 2C). Only 2% cation degradation was detected
for 10 under 1 M KOH/CD3OH conditions with Hofmann
elimination as the major degradation pathway. Consistent with
the trend of pyrrolidinium 9 versus piperidinium 6, we
observed faster degradation for spirocyclic cation 13 than for
10. In the case of five-membered ring, 13 mostly degraded
through SN2 ring-opening attack (Scheme 4). In addition,
another challenge related to spirocyclic piperidinium is how to
tether the cation onto polymers, as Jannasch and co-workers
envisioned that the substituents on piperidinium cations would
rigidify the rings and decrease the stability.41 Thus, spirocyclic
piperizinium is a potential candidate, as the tertiary amine
could act as a linker (11, 12, and 14 in Scheme 4).43 However,
faster degradation than 10 was detected, and a plausible
pathway is shown in Scheme 5. It is proposed that the extra
nitrogen atom accelerated the ring-opening Hofmann elimi-
nation, and the resultant enamine intermediate hydrolyzed
CH3OH for 30 days (Scheme 3). Both demethylation and
Hofmann elimination products were identified in the
degradation mixture, but due to their low concentrations, it
was difficult to identify whether the Hofmann elimination
occurred on the hexyl chain or the piperidinium ring.26 In
contrast, pyrrolidinium cation (9) exhibited faster degradation,
leaving just 33% of cation remaining after 1 M KOH/CH3OH
treatment for 30 days (Scheme 3).29 Two comparative
degradation pathways were identified from the 1H NMR
analysis, including methoxide SN2 ring-opening attack and
Hofmann elimination generating pyrrolidine and ethylene. The
proposed ring-opened product was confirmed by HRMS
(Figure S35). The advantages of this protocol are highlighted
by the alkaline-stability studies of these ammonium cations,15
Scheme 5. Proposed Major Degradation Pathways for
Piperizinium Cations
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thereafter (Scheme 5). As a result, the steric hindrance around
the nitrogen atoms played important roles on alkaline stability,
and the i-Pr substituted cation 11 showed significantly better
alkaline stability than cations 12 and 14.
In addition to ammonium cations, N-conjugated cations
have also been incorporated into a variety of AAEMs.20,21,44,45
These cations can potentially demonstrate higher chemical
stabilities, because the positive charge is delocalized and
stabilized by resonance; however, N-conjugated cations have
additional degradation pathways, and judicious design is
required to improve their alkaline stability (Scheme 6 and
DMSO conditions.19,20 The results summarized in Scheme 6
highlight the impact of substituent choice on the alkaline
stability of N-conjugated cations.
Other types of N-conjugated cations, including benzimida-
zolium, benzotriazolium, pyridinium, and guanidinium, have
also been studied using our standard protocol (Scheme 7 and
Scheme 7. Stability Results of Non-Imidazolium N-
Conjugated Cations (19−22) Under 1 M and 2 M KOH/
CD3OH 80 °C Conditions. Numbers in Parentheses
Indicate 2 M KOH/CD3OH
Scheme 6. Stability Results of Imidazolium Cations (15−
18) under 1 M and 2 M KOH/CD3OH 80 °C Conditions.
Numbers in Parentheses Indicate 2 M KOH/CD3OH
a
5 days.
Figures 1E and 2E). Holdcroft and coworkers have prepared a
series of benzimidazolium-functionalized AAEMs of which
model compound 19 is a representative example.47,48 The C2
position is substituted by a 2,4,6-trimethylphenyl group to
inhibit nucleophilic attack, which is the same strategy for
imidazolium cation 15. However, hydroxide can still initiate
nucleophilic ring-opening attack and demethylation of 19,
indicating that benzimidazolium is not as alkaline stable as the
corresponding penta-substituted imidazolium cations (Scheme
7).31,49 When the C2 position of imidazolium is replaced by a
nitrogen atom, the cation turns into a triazolium.50 We
subjected benzotriazolium 20 under the KOH/CD3OH
conditions and observed deethylation as the major degradation
product at a much faster rate than imidazolium 15 and
benzimidazolium 19 (Scheme 7). The benzotriazole product
was confirmed by HRMS, but we are currently unable to
confidently assign the degradation mechanism, as neither
ethylene nor ethanol was observed in comparative amount,
while a broad range of unidentifiable peaks were present
throughout the 1H NMR spectra after alkaline stability studies
(Figure S61). Pyridinium is another common cyclic N-
conjugated cation, yet model compound 21 degraded rapidly
in 1 M KOH/CD3OH with benzyl amine as the only
identifiable degradation product (Scheme 7). The proposed
degradation mechanism is shown in Scheme 8, which includes
nucleophilic aromatic attack on pyridinium, 6π-electrocyclic
ring opening, and sequential hydrolysis.51 Rapid hydrolysis was
also observed when noncyclic N-conjugated cation, guanidi-
nium (22), was treated with standard alkaline conditions, and
a
b
c
15 days. 10 days. 5 days.
Figures 1D and 2D).31 For example, 1-benzyl-3-methylimida-
zolium (18) showed no evidence of degradation products from
SN2 of benzyl or methyl groups by H NMR analysis, while it
1
decomposed into benzyl amine, methyl amine, formate salt,
and hydrated glycolaldehyde (Scheme 6). This observation is
consistent with recent imidazolium decomposition studies by
Pellerite et al. under slightly different conditions,13 and the
degradation is likely initiated by nucleophilic addition to the
C2 position (N−CN) followed by complete enamine and
amide hydrolysis (Scheme 1).31 When the C2 position was
substituted with a methyl group (17), the degradation was
slower, but the degradation products were similar (Scheme
6).13,46 Model compound 16 was designed to block the C2
position from nucleophilic attack by incorporating a bulky 2,6-
dimethylphenyl substituent.14 The alkaline stability of 16 was
significantly higher, and only degradation products from SN2
attack on the benzyl and methyl groups were identified without
ring-opening/imidazolium-hydrolysis products (Scheme 6).
When the labile benzyl and methyl groups were replaced by
n-butyl groups, the imidazolium cations (15) became
extremely stable under our KOH/CD3OH conditions, and
no degradation products could be detected by 1H NMR
spectroscopy (Scheme 6).14 It is noteworthy that Hofmann
elimination of the n-butyl groups can be the major degradation
pathway of cation 15 under more aggressive KOH/anhydrous
1
several hydrolysis intermediates were identified by H NMR
analysis (Scheme 7).52 The degradations of 21 and 22 are both
initiated by nucleophilic addition on the iminium carbon,
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harsher alkaline treatment (i.e., 2 M KOH/2-(2-
methoxyethoxy)ethanol at 160 °C or 50 wt % NaOH/H2O
phase-transfer in chlorobenzene at 100 °C), both tetrakisami-
nophosphonium cations would degrade mostly through
Cahours−Hofmann phosphine oxidation.10
Scheme 8. Proposed Major Degradation Pathways for
Pyridinium Cations
CONCLUSION
■
A standard protocol to analyze cation alkaline degradation in
CD3OH has been reported, and herein, we use the protocol to
understand the degradation mechanisms of 26 cations under
the same set of conditions. Their alkaline stability trend can be
summarized as follows. For ammonium cations, benzyl
nucleophilic substitution would dominate when available,
while SN2 elsewhere and Hofmann elimination are also valid
degradation pathways. For N-conjugated cations, SN2 and
Hofmann elimination are less problematic than nucleophilic
addition to the iminium carbon centers. For these compounds,
the steric hindrance plays an important role in improving the
alkaline stability. Further hydrolysis and rearrangement are also
common for N-conjugated cations. For phosphonium cations,
Cahours−Hofmann phosphine oxidation is a unique, yet rapid
degradation route, thus sterically bulky substituents near the
phosphorous can significantly decelerate this pathway.
Attention needs to be made when using electron-rich aromatic
substituents on phosphorous, as ether hydrolysis will likely
occur under alkaline conditions. Tetrakisaminophosphonium is
one of the most stable scaffolds as organic cations. The power
of this protocol is underscored by the broad scope of cations
and the clear degradation mechanism assignment. We are also
delighted to notice that this protocol has been used by the
Swager group and the Tang group to identify new cation
candidates (i.e., pyrazolium17 and cobaltocenium,18 respec-
tively) for AAEMs. More recently, Mustain et al. prepared
AEMFCs assembled with alkyltrimethylammonium-function-
alized AAEMs and ionomers,56 which outperformed previous
BTMA-based ones,57 and it was the first AEMFC to meet the
US Department of Energy requirements to operate stably at
current density of 600 mA cm−2 for 2000 hours.56 With the
alkaline-stable cations in hand and their possible degradation
pathways in mind, our future goal is to install these cations into
polymeric structures to develop durable AAEMs and fuel cell
devices for green energy conversion applications.
rather than nucleophilic substitution on the methyl or benzyl
groups. These results suggest that one fundamental strategy for
enhanced alkaline stability is to increase the steric hindrance
and prohibit the potential nucleophilic attack on the
electrophilic sp2 carbon centers, and this is exactly what
Zhang et al. recently revealed in their systematic alkaline
stability studies of various guanidinium derivatives.16
Phosphorus is a neighboring member of nitrogen in Group
15 elements, thus its corresponding cation, phosphonium, has
also been involved in various AAEM structures (Scheme 9 and
Scheme 9. Stability Results of Phosphonium Cations (23−
26) Under 1 M and 2 M KOH/CD3OH 80 °C Conditions.
Numbers in Parentheses Indicate 2 M KOH/CD3OH
a
5 days.
Figures 1F and 2F).53−55 In comparison to BTMA (2),
benzyltrimethylphosphonium cation 26 degraded much faster
via a distinct mechanism (Scheme 9). Rather than SN2 attack,
degradation was initiated by the nucleophilic attack of
hydroxide on the phosphorous center, leading to phosphine
oxidation (Cahours-Hofmann reaction, also see Scheme 1).2
The observed degradation products are toluene and
trimethylphosphine oxide.22 As reported by Yan et al,
phosphine oxidation can be inhibited by integrating bulky
and electron-rich aromatic rings (25).22 Neither phosphine
oxidation nor nucleophilic benzyl substitution were detected
by 1H NMR analysis when 25 was treated with KOH. Instead,
the methoxy substituents on the aromatic ring were attacked
by both methoxide and hydroxide, giving rise to ether
hydrolysis products (Scheme 9).22 To further improve the
alkaline stability of phosphonium cations, the phosphorous
atom can be substituted by four amino groups to give
tetrakisaminophosphonium cations like 23 and 24, which are
elegantly stabilized by both resonance and steric hindrance.
Under our standard KOH/CD3OH protocol conditions,
neither bulky 23 nor hydrophilic 24 showed detectable
degradation (Scheme 9). It is noteworthy that with even
EXPERIMENTAL SECTION
■
Methods and Instruments. 1H and 13C NMR spectra were
recorded on a Bruker 400, Varian INOVA 500 or 600 MHz
instrument at 22 °C with shifts reported relative to the residual
solvent peak (CD3OD or CD3OH); 3.31 ppm (1H) and 49.00 ppm
(13C). Electrospray ionization−high-resolution mass spectrometry
(ESI-HRMS) analyses were performed on a Bruker 9.4 T solariX
Fourier-transform ion cyclotron resonance mass spectrometry (FT-
ICR-MS) instrument. Direct analysis in real timehigh-resolution
mass spectrometry (DART-HRMS) analysiswas performed on a
Thermo Scientific Exactive Orbitrap MS system equipped with an Ion
Sense DART ion source.
Solvent Suppression Procedure. Quantitative 1H NMR spectra
for model compound stability studies were acquired in CD3OH to (1)
prevent unwanted hydrogen/deuterium exchange in model com-
pounds and degradation products and (2) improve the solubility of
model compounds and degradation products.29,58,59 The −OH signal
in CD3OH was suppressed by presaturation with a 2 second
presaturation delay and continuous wave irradiation with decoupler
field strength (γB1) of 113 Hz (equivalent to a presaturation power of
9). Spectra were acquired over a spectral width of −1 to 14 ppm with
60 s relaxation delay and nominal 90° excitation pulse. Sixteen scans
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were averaged for each analysis. NMR spectra were processed using
MestReNova Version 14.0.0-23239 (Mestrelab Research S.L).
Whittaker smoother baseline correction was applied, and linear
correction was used for all integrals. Note that residual signals
between 5.5 and 6.5 ppm often derive from solvent suppression and
shift depending on sample pH.
117.6, 60.6, 59.7, 43.8, 22.6, 20.4; HRMS (ESI) m/z: [M − Br]+
Calcd for C15H23N2: 231.1856; Found 231.1856.
1,3-Diethyl-1H-benzo[d][1,2,3]triazol-3-ium iodide (20). Ac-
cording to the general procedure, benzotriazole (2.0 mmol, 1.0
equiv), ethyliodide (4.4 mmol, 2.2 equiv), K2CO3 (2.4 mmol, 1.2
equiv), and 10 mL MeCN were used to synthesize the title compound
20 as white solid (298 mg, 49% yield). 1H NMR (400 MHz,
CD3OD): δ 8.36−8.28 (m, 2H), 8.03−7.96 (m, 2H), 5.07 (q, J = 7.3
Hz, 4H), 1.79 (t, J = 7.3 Hz, 6H); 13C{1H} NMR (100 MHz,
CD3OD): δ 136.2, 132.3, 114.8, 48.6, 14.3; HRMS (ESI) m/z: [M −
I]+ Calcd for C10H14N3: 176.1182; Found 176.1183.
Chemicals. 3-(Trimethylsilyl)-1-propanesulfonic acid sodium salt
(NaDSS) (TCI Chemicals), methanol-d3 (Acros), methanol-d4
(Cambridge Isotope Laboratories), potassium hydroxide (Mallinck-
rodt), tetrabutylammonium bromide (7), and tetradecyltrimethylam-
monium bromide (8) (Sigma-Aldrich) were all used as received. The
model compounds were prepared according to literature procedures:
1-benzylquinuclidin-1-ium bromide (1);60 benzyltrimethylammonium
bromide (2);14 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium bromide
(3);61 4-benzyl-4-methylmorpholin-4-ium bromide (4);61 N-benzyl-
N-cyclohexyl-N-methylcyclohexanaminium bromide (5);11 1-hexyl-1-
methylpiperidin-1-ium bromide (6);62 1-ethyl-1-methylpyrrolidin-1-
ium bromide (9);63 6-azaspiro[5.5]undecan-6-ium bromide (10);9 5-
azaspiro[4.5]decan-5-ium bromide (13);42 1,3-di-n-butyl-2-(2,6-di-
methylphenyl)-4,5-diphenylimidazolium iodide (15);14 1-benzyl-2-
(2,6-dimethylphenyl)-3-methyl-4,5-diphenylimidazolium (16);14 1-
benzyl-2,3-dimethylimidazolium bromide (17);14 1-benzyl-3-methyl-
imidazolium bromide (18);14 1,3-dimethyl-2-mesityl-1H-benzimida-
zolium iodide (19);64 1-benzylpyridin-1-ium chloride (21);65 N-
[bis(dimethylamino)methylene]-N-methyl-1-phenylmethanaminium
iodide (22);66 tetrakis[cyclohexyl(methyl)amino]phosphonium hexa-
fluorophosphate (23),67 tetrakis(pyrrolidin-1-yl)phosphonium hexa-
fluorophosphate (24);10 benzyl-tris(2,4,6-trimethoxyphenyl)-
phosphonium bromide (25);68 and benzyltrimethylphosphonium
bromide (26).69
Model Compound Study Procedures. Stock solutions of basic
methanol were prepared by dissolving KOH (1 M or 2 M) and 3-
(trimethylsilyl)-1-propanesulfonic acid sodium salt (0.0250 M) in
CD3OH.15,29 For example, a 1 M solution was prepared by dissolving
KOH (142 mg, 2.51 mmol) and NaDSS (13.6 mg, 0.0625 mmol) in
2.50 mL of CD3OH. The model compound (0.05 M for 1 M KOH
and 0.03 M for 2 M KOH) was dissolved in the methanol solution
(0.50 mL) and passed through a glass wool plug into an NMR tube.
The NMR tube was flame-sealed and analyzed by 1H NMR
spectroscopy for the initial time point. Integration of a selected
signal in the model compound relative to a signal related to 3-
(trimethylsilyl)-1-propanesulfonic acid sodium salt provided the initial
quantity of model compound. The tube was heated in an oil bath at
80 °C. At specified time points, every 5 days, the tubes were removed,
cooled to room temperature, and analyzed by 1H NMR spectroscopy
to determine the quantity of model compound remaining (1H NMR
1
spectra are provided). The H NMR spectra of 15, 16, 23, and 24
under standard protocol conditions (1 M and 2 M KOH in CD3OH
at 80 °C for 30 days) were previously reported.10,14 The final cation
percentage remaining results were covered in our previous viewpoint.15
General Model Compound Synthesis Procedure. A modified
literature procedure was used.9 To a predried 50 mL Teflon-lined
seal-tube was added K2CO3 (2.4 mmol, 1.2 equiv). The flask was left
under vacuum for 10 min, and then refilled with N2. This process was
repeated three times, followed by the addition of the corresponding
nucleophile (2.0 mmol, 1.0 equiv), alkyl halide, and MeCN (10 mL).
The tube was then sealed under N2 and warmed up to 80 °C, and the
reaction was maintained under stirring at 80 °C for 16 h. After cooling
to 22 °C, the mixture was diluted with CH2Cl2 and filtered through
cotton. The filtrate was then concentrated and triturated in Et2O to
afford the model compounds as white solids.
3-Isopropyl-3,6-diazaspiro[5.5]undecan-6-ium bromide
(11). According to the general procedure, 1-isopropylpiperazine
(2.0 mmol, 1.0 equiv), 1,5-dibromopropane (2.0 mmol, 1.0 equiv),
K2CO3 (2.4 mmol, 1.2 equiv), and 10 mL MeCN were used to
synthesize the title compound 11 as white solid (466 mg, 84% yield).
1H NMR (400 MHz, CD3OD): δ 3.57−3.45 (m, 8H), 2.91−2.76 (m,
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02051.
■
sı
Expanded data table, NMR and HRMS spectra, and
degradation product assignment (PDF).
AUTHOR INFORMATION
Corresponding Authors
■
Kevin J. T. Noonan − Department of Chemistry, Carnegie
Mellon University, Pittsburgh, Pennsylvania 15213-2617,
United States; orcid.org/0000-0003-4061-7593;
Email: noonan@andrew.cmu.edu
Geoffrey W. Coates − Department of Chemistry and
Chemical Biology, Baker Laboratory, Cornell University,
Ithaca, New York 14853-1301, United States; orcid.org/
0000-0002-3400-2552; Email: coates@cornell.edu
5H), 1.96−1.84 (m, 4H), 1.79−1.66 (m, 2H), 1.10 (d, J = 6.5 Hz,
6H); 13C{1H} NMR (100 MHz, CD3OD): δ 60.8 (br), 60.3, 55.3,
43.0, 22.6, 20.4, 18.8; HRMS (ESI) m/z: [M − Br]+ Calcd for
C12H25N2: 197.2012; Found 197.2011.
3-Methyl-3,6-diazaspiro[5.5]undecan-6-ium bromide (12).
According to the general procedure, 1-methylpiperazine (2.0 mmol,
1.0 equiv), 1,5-dibromopropane (2.0 mmol, 1.0 equiv), K2CO3 (2.4
mmol, 1.2 equiv), and 10 mL MeCN were used to synthesize the title
Authors
Wei You − Department of Chemistry and Chemical Biology,
Baker Laboratory, Cornell University, Ithaca, New York
14853-1301, United States; Beijing National Laboratory for
Molecular Sciences (BNLMS), CAS Key Laboratory of
Engineering Plastics, Institute of Chemistry, Chinese Academy
of Sciences, Beijing 100190, China; orcid.org/0000-0002-
8698-309X
Kristina M. Hugar − Department of Chemistry and Chemical
Biology, Baker Laboratory, Cornell University, Ithaca, New
York 14853-1301, United States; orcid.org/0000-0003-
1380-0747
1
compound 12 as white solid (256 mg, 51% yield). H NMR (400
MHz, CD3OD): δ 3.61−3.45 (m, 8H), 2.77 (t, J = 5.3 Hz, 4H), 2.40
(s, 3H), 1.91 (p, J = 6.0 Hz, 4H), 1.78−1.67 (m, 2H); 13C{1H} NMR
(100 MHz, CD3OD): δ 60.7 (br), 59.7, 48.6, 45.2, 22.6, 20.4; HRMS
(ESI) m/z: [M − Br]+ C10H21N2 169.1699; Found 169.1699.
3-Phenyl-3,6-diazaspiro[5.5]undecan-6-ium bromide (14).
According to the general procedure, 1-phenylpiperazine (2.0 mmol,
1.0 equiv), 1,5-dibromopropane (2.0 mmol, 1.0 equiv), K2CO3 (2.4
mmol, 1.2 equiv), and 10 mL MeCN were used to synthesize the title
1
compound 14 as white solid (280 mg, 45% yield). H NMR (400
MHz, CD3OD): δ 7.29 (t, J = 7.7 Hz, 2H), 7.04 (d, J = 8.1 Hz, 2H),
6.92 (t, J = 7.3 Hz, 1H), 3.70 (t, J = 5.2 Hz, 4H), 3.58 (t, J = 5.8 Hz,
4H), 3.51 (t, J = 5.2 Hz, 4H), 1.95 (p, J = 6.0 Hz, 4H), 1.76 (p, J = 6.1
Hz, 2H); 13C{1H} NMR (100 MHz, CD3OD): δ 150.9, 130.3, 122.1,
Ryan C. Selhorst − Department of Chemistry, Carnegie
Mellon University, Pittsburgh, Pennsylvania 15213-2617,
United States
G
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Article
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Megan Treichel − Department of Chemistry, Carnegie Mellon
University, Pittsburgh, Pennsylvania 15213-2617, United
States
Cheyenne R. Peltier − Department of Chemistry and
Chemical Biology, Baker Laboratory, Cornell University,
Ithaca, New York 14853-1301, United States; orcid.org/
0000-0003-4654-2051
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02051
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Author Contributions
§W.Y. and K.M.H. contributed equally to this work.
Notes
The authors declare the following competing financial
interest(s): K.M. Hugar and G.W. Coates are cofounders of
Ecolectro, and hold an equity stake in the company.
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ACKNOWLEDGMENTS
■
This work was primarily supported as part of the Center for
Alkaline-based Energy Solutions (CABES), an Energy Frontier
Research Center funded by the U.S. Department of Energy,
Office of Science, Basic Energy Sciences under Award # DE-
SC0019445. M.T. and K.J.T.N. also acknowledge the support
from National Science Foundation (NSF, CHE-1809658) for
the synthesis of cations 10 and 13. This study made use of the
NMR facility supported by NSF Grant CHE-1531632. We
1
thank Dr. I. Keresztes for assistance with interpretation of H
NMR spectroscopy results and for helpful discussions. We
thank S. Li (Boston University) for designing and drawing the
TOC figure.
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