Synthesis and thermochemical properties of stereoisomeric dihydroxy- and tetrahydroxyalkylammonium salts

Article abstract of DOI:10.1055/s-0028-1088163

A series of stereoisomeric ammonium salts containing the 1,2-dihydroxypropyl unit were prepared. Of particular interest to us are those salts that were found to be ionic liquids, although some are solids at room temperature. The thermochemical properties

Full text of DOI:10.1055/s-0028-1088163

PAPER
1437
Synthesis and Thermochemical Properties of Stereoisomeric Dihydroxy- and
Tetrahydroxyalkylammonium Salts
S
ynthesis and Thermoc
a
hemical Pr
r
operties
i
of Hyd
e
roxy Ammonium
T
Salts homas,a,b Leah Rothman,a Jasmine Hatcher,a,c Pooja Agarkar,a Rabindra Ramkirath,a
Sharon Lall-Ramnarine,c Robert Engel*a
a
Department of Chemistry and Biochemistry, Queens College, CUNY, 65-30 Kissena Boulevard, Flushing, NY 11367, USA
Fax +1(718)9975531; E-mail: robert.engel@qc.cuny.edu
Doctoral Program in Chemistry, The Graduate Center, CUNY, 365 5th Avenue, New York, NY 10016, USA
Department of Chemistry, Queensborough Community College, CUNY, 222-05 56th Avenue, Bayside, NY 11364, USA
b
c
Received 13 October 2008; revised 16 December 2008
in a compound with varied physical properties, and these
Abstract: A series of stereoisomeric ammonium salts containing
properties of the ionic liquid can therefore be manipulated
by choosing a particular cation and anion. Because of this
variability in properties based on structure, ionic liquids
have been referred to as designer solvents.8
the 1,2-dihydroxypropyl unit were prepared. Of particular interest
to us are those salts that were found to be ionic liquids, although
some are solids at room temperature. The thermochemical proper-
ties of these new materials are reported.
Key words: ionic liquids, chirality, dicyanamides, bistriflimides,
phosphates
R
N+
R
R
+
Me
N
N
R
R
R
P
R
R
+
N
+
R
Me
R
Quaternary ammonium salts have a wide range of interest-
ing properties and applications. Past studies by this labo-
ratory include the development of ammonium salts that
can be used as phase-transfer catalysts, antihydrophobic
agents, and antimicrobial agents.1–4 More recently, we
have studied various structural types of quaternary ammo-
nium salts as ionic liquids. Ionic liquids (ILs) are pure
salts that have a melting point below 100 °C.5,6 As ILs,
these salts must be in a non-aqueous, liquid state and
should not contain any additional neutral molecules.5
These two requirements rule out classical molten salts and
aqueous salt solutions as ILs. Although the differentiation
between ILs and molten salts or salt solutions seems arbi-
trary, the division lies in the large number of applications
that are solely for ILs. For instance, the extremely high
melting point of molten salts makes them very difficult to
work with and leads to incompatibilities with many reac-
tions.7 Salt solutions do not have the same problem as
molten salts; however, their applications are much more
limited compared to ILs as the solvent plays a critical role
in their behavior.
Cl–, Br–, BF4–, PF6–, NTf2
–
Figure 1 Common cations and anions: 1-alkyl-3-methylimidazoli-
um, tetraalkylammonium, tetraalkylphosphonium, 1-alkyl-1-methyl-
pyrrolidinium, chloride, bromide, tetrafluoroborate, hexafluoro-
phosphate, and bis(trifluoromethylsulfonyl)imide
Ionic liquids in general are thermally stable, have a wide
liquidus range, can exhibit high conductivities, and are
usually recyclable to some extent. Most ILs also exhibit a
low vapor pressure and therefore do not contribute to air
pollution. Due to the ability to recycle these materials and
their relative nonvolatility, ILs have received much atten-
tion as potential greener solvents. In addition, ILs have
generated much interest due to their electrochemical prop-
erties and their properties with regard to radionuclides,
and as possible replacements for volatile organic com-
pounds (referred to as VOCs) currently in use. Much of
the prior literature on ILs has been concerned with their
use as solvents in organic synthesis and as catalysts for a
range of organic reactions.9–12 In addition to being used in
synthesis, ILs can be used in chemical analyses (e.g.,
chromatography and electrophoresis), in large-scale sepa-
rations, and as media for electrochemical processes. They
can also be used as engineering fluids and performance
additives.13
Ionic liquids are typically synthesized from large organic
cations and relatively small organic or inorganic anions.
Common cations include N,N¢-dialkylimidazolium, tetra-
alkylammonium, tetraalkylphosphonium, and N-meth-
ylpyrrolidinium, while common anions include halides,
tetrafluoroborate, and bis(trifluoromethylsulfonyl)imide
(see Figure 1). There are a great variety of ILs that can po-
tentially be made, due to the limitless number of possible
cation and anion combinations. Each combination results
The focus of our most recent studies involving quaternary
ammonium salts has been on chiral ionic liquids. Chiral
ionic liquids have the potential to provide selectivity in
asymmetric synthesis, chiral separations, resolutions, and
electrochemical processes.14 Chiral ionic liquids are usu-
ally made from precursors derived from the readily avail-
able chiral pool of chemical adjuncts. Chirality can
originate with either the cation and/or the anion. Materials
developed so far have found use as chiral solvents for
SYNTHESIS 2009, No. 9, pp 1437–1444
x
x
.
x
x
.2
0
0
9
Advanced online publication: 25.03.2009
DOI: 10.1055/s-0028-1088163; Art ID: M06108SS
© Georg Thieme Verlag Stuttgart · New York

1438
M. Thomas et al.
PAPER
asymmetric synthesis and stereoselective polymerization, and the salt separates from the aqueous solution.19 The salt
chiral phases for gas chromatography, chiral shift reagents is washed with water until there is no presence of halide
for NMR spectroscopy, and chiral liquid crystals.15
detected. In many cases this change in the anion did result
in lower melting points and lower viscosities of these ma-
terials, while maintaining an anion that is relatively ‘non-
degradable’ to toxic products.
We now report the development of a series of quaternary
ammonium salts based on the potentially chiral auxiliary
3-chloropropane-1,2-diol, also known as a-chlorohydrin,
with the goal of synthesizing some new ILs. This auxiliary Racemic phosphate and bistriflimide salts were synthe-
was chosen because it is readily available and some inter- sized and, in addition, we have also developed dicyana-
esting products could be developed from it. Also, since mide and diphenyl phosphate salts. Dicyanamide salts are
carbon–carbon bond-forming reactions such as the Diels– prepared by reaction of the halide salt with silver dicyan-
Alder reaction, Michael additions, or the Baylis–Hillman amide in water. The resulting silver salt is removed by fil-
reaction could be influenced by hydrogen bonding, these tration and the aqueous solvent is evaporated.20 The
salts might be useful solvents and/or catalysts in these diphenyl phosphate salts are generally made by the reac-
types of reactions. Such reactions are widely used in the tion of a charge equivalent amount of diphenyl phosphate
preparation of natural products and biologically active and potassium hydroxide with the halide salt in ethanol.
compounds. Thus, there is great interest in finding ways The potassium salt is removed by filtration and the etha-
of enhancing rates and selectivity.
nol is evaporated, leaving the diphenyl phosphate salt.
We have performed developmental work with the racemic 3-Chloropropane-1,2-diol was combined with a variety of
alkyl halide 3-chloropropane-1,2-diol and have extended tertiary amines, such as 1,4-diazabicyclo[2.2.2]octane
these efforts to the optically active species. Our goal has (DABCO), 4-(dimethylamino)pyridine (DMAP), 1-meth-
been to generate a series of salts, and to determine which ylpyrrolidine, N,N,N¢,N¢-tetramethylhexane-1,6-diamine,
have the best properties (low viscosity, wide liquidus N,N,N¢,N¢-tetramethylpropane-1,3-diamine,
and
range, etc.) for particular applications. Although the phys- N,N,N¢,N¢-tetramethylbutane-1,3-diamine, to form the ha-
ical characteristics of racemates compared to individual lide salts. As a general trend, the halide salts could be pu-
enantiomers are anticipated to differ, the intent has been rified simply by washing with an appropriate solvent. In
that synthesis of the chiral analogues of those liquids this way, the other salts, such as the phosphates, bistrifl-
would proceed in a corresponding manner. A few of the imides, and dicyanamides, could be formed relatively
chiral analogues have been successfully synthesized.16 So pure with little need for further purification. All new salts
far, they have been found to exhibit lower melting points were dried for several days under high vacuum and their
than their racemic analogues.
structures were verified using 1H, 13C, and, where appro-
priate, 31P NMR spectroscopy. Spectroscopic data and el-
emental analysis for the various salts are presented in
Tables 1– 4. The structures of the various cations with the
stereogenic centers labeled are presented in Figure 2. The
anions are shown in Figure 3. Each cation has been as-
signed a letter and each anion has been assigned a number,
by which the salts are designated.
Previous studies by this laboratory have involved the syn-
thesis of two classes of ILs: liquid ionic phosphates (LIPs)
which contain the phosphate anion, and polyammonium
ionic liquid sulfonylimides (PILS) containing the anion
bis(trifluoromethylsulfonyl)imide (also known as bistrifl-
imide).17,18 The synthesis of ILs usually starts with the
generation of a halide salt, itself formed through an SN2
reaction between a tertiary amine and an alkyl halide.
Then, through anion metathesis reactions with either a
protic acid or a metal salt, other salts (which presumably
would be liquid) are formed. For example, LIPs are made
by using a charge equivalent amount of pure phosphoric
acid in anhydrous methanol or ethanol. The solvent is then
evaporated. LIPs, which are considered hydrophilic, have
the particularly desirable characteristic of being more
‘green’ than other common types of ILs. That is, the anion
does not degrade to toxic materials upon contact with oth-
er solvents, and relatively little energy is consumed in
their preparation. However, many of these materials are
extremely viscous and/or have high melting points, mak-
ing both their characterization and use in practical appli-
cations difficult. This difficulty led to the synthesis of the
corresponding PILS.
∗
N+
∗
+
Me2N
OH
N
N
OH
OH
OH
A
B
OH
OH Me
Me
N+
∗
+
+N
∗
∗
OH
N
Me
Me
OH
Me
OH
OH
D
C
Me
N+
OH
Me
N+
Me
N+
OH
OH Me
OH
N+
∗
∗
∗
∗
∗
Me
Me
Me
Me
OH
OH
OH
OH
E
F
Figure 2 Cations examined in this study: 1-(2,3-dihydroxypropyl)-
4-aza-1-azoniabicyclo[2.2.2]octane (A); 1-(2,3-dihydroxypropyl)-4-
(dimethylamino)pyridinium (B); 1-(2,3-dihydroxypropyl)-1-methyl-
pyrrolidinium (C); 4,4,11,11-tetramethyl-4,11-diazoniatetradecane-
1,2,13,14-tetrol (D); 4,4,8,8-tetramethyl-4,8-diazoniaundecane-
1,2,10,11-tetrol (E); 4,4,5,8,8-pentamethyl-4,8-diazoniaundecane-
1,2,10,11-tetrol (F); the stereogenic sites are labeled with a star.
Polyammonium ionic liquid sulfonylimides are made
from the corresponding halide salts by using a charge
equivalent amount of lithium bis(trifluoromethylsulfo-
nyl)imide in water. Bistriflimides tend to be hydrophobic
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

PAPER
Synthesis and Thermochemical Properties of Hydroxy Ammonium Salts
1439
O
trogen atoms in salts D1 and D4 (d 65.3 and 65.6 for D1,
65.6 and 66.1 for D4; see Tables 1 and 4); however, with
the salt D3, only one signal is observable for these methyl-
ene carbons a to the nitrogens (d 64.0; see Table 3). In nei-
ther salt D3 nor D4 was differentiation evident for the ste-
reogenic carbon sites in the anion.
–
3–
O
S
O
P
O
O
S
–
N
F3C
O
CF3
O
P
O
2
Cl–
1
O
NC
CN
N
O
O
O
–
4
3
5
In the instances of salts derived from cation E (with a
shorter connecting chain between the cationic sites), for
the halide salt E1 two resonances each for the methyl and
internal ammonium salt carbon sites could be observed
(d 51.9, 52.1 and 61.2, 61.4, respectively; see Table 1) and
for the dicyanamide salt E4 two resonances could be ob-
served for three separate categories of ammonium carbon
atoms (d 51.8, 52.0: the methyl carbons on the nitrogens;
61.1, 61.3: internal methylene carbons next to the nitrogen
atoms; 66.0, 66.1: the carbons with the secondary hydroxy
groups; see Table 4). In constrast, diastereotopic carbon
sites could not be differentiated in the case of the bis-
triflimide salt E3 (see Table 3). This is in keeping with the
observations for the salts derived from cation D, in which
the bistriflimide salt exhibited the greatest positional vari-
ability while the halide and dicyanamide salts were posi-
tionally less variant.
Figure 3 Anions examined in this study: chloride (1); phosphate
(2); bis(trifluoromethylsulfonyl)imide (3); dicyanamide (4); diphenyl
phosphate (5)
As demonstrated by their melting points (see Table 5),
most of the salts are solid at room temperature. Melting
points were determined using a capillary melting point ap-
paratus for the solids and/or differential scanning calorim-
etry (DSC) for those salts that are liquid at room
temperature. All of the halide salts are high-melting solids
(A1, B1, C1, D1, and E1). The salt F1 was prepared, but
this glassy material contained the starting alkyl halide, a-
chlorohydrin, which could not be readily separated. The
pyridinium salt B1 has the highest melting point range
(204–207 °C). The halide salt with the lowest melting
point (105 °C) is the pyrrolidinium compound C1. The ha-
lide salts are only soluble in water and alcohols, such as
methanol and ethanol.
Finally, with the bistriflimide salt F3, wherein three ste-
reogenic carbon sites are present, produced from two ra-
cemic reagents, rapid rotational variance is evident as
The phosphates (A2, B2, C2, and D2) and diphenyl phos-
phates (A5, B5, and D5) are generally also high-melting
salts. In general, the melting points are lower than those of
the corresponding halide salts. The phosphates are quite
hydrophilic, while the diphenyl phosphates appear to be
less hydrophilic. All of these salts are solid at room tem-
perature, except for C5. This compound is a viscous liquid
at room temperature and has a glass transition of –28 °C.
diastereoisomeric differences are not observed in the 13
C
NMR spectrum. This, again, is in keeping with the obser-
vations for the bistriflimide salts of other cations.
All the bistriflimide salts (B3, D3, E3, and F3) are viscous
ILs. As previously mentioned, bistriflimides tend to be
hydrophobic but the hydroxy salts presented here are am-
phiphilic in nature. Because of this, a sizable quantity of
the salts was lost during purification. An attempt was
made to synthesize A3 and C3, but these salts are water
soluble and the halide impurity could not be separated.
The synthesis and purification of the bistriflimides were
described previously. Most of the bistriflimide salts had
simple DSC traces, which displayed only a glass transi-
tion. Only B3 (a solid at room temperature) exhibited a
melting point (49.1 °C) and a glass transition. The DSC
trace for this ionic liquid is shown in Figure 4.
The observed stereochemical characteristics of several of
the salts are worthy of mention. Salts of cations A, B, and
C are racemic mixtures, those of cation C thus bearing
diastereotopic carbon sites within the pyrrolidinium ring
system that can not become magnetically equivalent by
rotation or inversion about nitrogen. In the 13C NMR spec-
trum of halide salt C1, the b-carbons of the ring could be
differentiated (d 20.5 and 21.3; see Table 1), although not
the a-carbons; however, in the case of the dicyanamide
salt C4, both the diastereotopic b- and a-carbon sites of
the ring could be differentiated (d 20.6 and 21.5, along
with 66.6 and 66.8; see Table 4). It would thus appear
that, in the dicyanamide salts, the cation and anion have
less positional variability.
Bistriflimide salt F3 was prepared from the F1 mixture
(salt F1 and a-chlorohydrin). The starting material and ha-
lide impurity were removed by washing with water. It
may be the situation that purification should be delayed to
the final product, rather than completed at intermediate
stages.
In the instances of salts derived from cation D, two stereo-
genic centers are present leading to three stereoisomeric
forms. These salts consist of both a racemic mixture and a
meso structure. In the instances of the halide salt D1, the
bistriflimide salt D3, and the dicyanamide salt D4, two
signals can be observed in the 13C NMR spectra for the
sets of diastereotopic methyl groups attached to the two
nitrogens (d 51.5 and 51.7 for D1 and D4, 51.1 and 51.2
for D3; see Tables 1, 3, and 4). Two signals are also ob-
served for the two sets of methylene carbons a to the ni-
The dicyanamide salts (A4, C4, D4, and E4) are liquids at
room temperature. The exception is B4, which has a melt-
ing point range of 105–106 °C. The ILs also had fairly
simple DSC traces that showed only a glass transition.
The salts are hydrophilic and only dissolve in protic polar
solvents. These liquids are not as viscous as the bistrifl-
imide salts. Since these liquids were soluble only in water
and alcohols, the existence of a halide impurity can not be
ruled out.
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

1440
M. Thomas et al.
PAPER
provide the greatest thermal stability is the (dimethylami-
no)pyridinium cation B, while cations A and D result in
salts with the lowest thermal stability. Most of the hy-
droxy ammonium salts exhibit moderate thermal stability.
Figure 4 DSC trace for bistriflimide salt B3
Listed in Table 5 are the thermochemical properties of the
hydroxyalkylammonium salts presented in this report,
along with the water content for the ILs. The thermal de-
composition onset temperatures of the ILs were deter-
mined through thermogravimetric analysis (TGA). These
temperatures indicate approximately the point at which
the ionic liquid begins to degrade. In general, the anion
appears to have a greater influence on the thermal stability
of the salts than the cation. For example, the dicyanamide
anion provides the salts with the lowest degradation tem-
peratures; thus, the degradation temperatures for A4, C4,
and D4 are 174 °C, 220 °C, and 222 °C, respectively. It
should be noted that dicyanamides tend to polymerize be-
fore degrading into smaller components.21 Evidence of
this was seen during our experiments (a large amount of
black solid residue remained after each experiment). Oth-
er anions such as diphenyl phosphate and bistriflimide re-
sult in salts with greater thermal stability. The diphenyl
phosphate salts have degradation temperatures that range
from 233 °C for D5 to 282 °C for B5. The bistriflimide
salts exhibit the highest thermal stability (403 °C for B3
and 363 °C for D3). Rogers and co-workers noted that the
onset of decomposition decreases with the increasing hy-
drophilicity of the anion.22 Our findings are consistent
with this observation. The TGA trace for bistriflimide salt
B3 is presented in Figure 5. The flat region between 20 °C
and 100 °C indicates that very little water is present in this
ionic liquid. The bistriflimide anion is known to produce
ILs with high thermal stability. The cation that seems to
Figure 5 TGA trace for bistriflimide salt B3
The chiral version of the hydroxy halide salt B1 was syn-
thesized but we were unable to obtain the chiral pyrroli-
dinium halide salt C1 in the pure form. In this case the
product was complexed with unreacted starting material
(a-chlorohydrin) that could not be removed. Melting
points were obtained for the pure chiral salts B1 using
DSC. The melting points are about 40 degrees Celsius
lower than the melting point of their racemic counterpart
(see Table 6). The S-enantiomer of B1 was converted into
the bistriflimide salt B3. This chiral salt is a liquid at room
temperature and the DSC trace revealed only a glass tran-
sition at 32.9 °C.
The successful synthesis of various types of stereoisomer-
ic quaternary ammonium salts has been accomplished.
Many of these salts have high melting points but some
were found to be ionic liquids. These materials have the
potential to be used as solvents in organic synthesis. The
best potential solvent seems to be bistriflimide salt B3. It
is easily prepared and, although a solid at room tempera-
ture, when heated to about 50 °C this ionic liquid exhibits
a lower viscosity compared to the other ionic liquids de-
veloped. In addition, this liquid has a relatively high deg-
radation temperature (403 °C).
Table 1 1H and 13C NMR Spectroscopic Data and Elemental Analysis for the Halide Salts
Compound
1H NMR data (400 MHz, D2O)
13C NMR data (100.6 MHz, Elemental analysis
D2O)
A1
d = 3.09 (t, J = 7.6 Hz, 6 H), 3.28 (m, 2 H), 3.40–3.52 (m, 8 H), d = 44.1, 53.2, 63.6, 65.2, Calcd for C9H19ClN2O2: C,
4.23–4.29 (br m, J = 2.4, 3.2 Hz, 1 H)
66.6
48.54; H, 8.60. Found: C, 48.14;
H, 8.36
B1
d = 3.06 (s, 6 H), 3.44–3.54 (m, J = 2.8, 4.4 Hz, 2 H), 3.87–3.97 d = 39.4, 59.4, 62.4, 70.6, Calcd for C10H17ClN2O2·H2O:
(m, J = 2.0, 2.4, 8.8 Hz, 2 H), 4.13–4.22 (m, 1 H), 6.73 (d, J = 8.0 107.4, 141.9, 156.4
Hz, 2 H), 7.84 (d, J = 7.6 Hz, 2 H)
C, 47.90; H, 7.64. Found: C,
47.83; H, 7.69
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

PAPER
Synthesis and Thermochemical Properties of Hydroxy Ammonium Salts
1441
Table 1 1H and 13C NMR Spectroscopic Data and Elemental Analysis for the Halide Salts (continued)
Compound
1H NMR data (400 MHz, D2O)
13C NMR data (100.6 MHz, Elemental analysis
D2O)
C1
d = 2.12 (br, 4 H), 3.02 (s, 3 H), 3.12–3.25 (m, J = 4.4, 9.6 Hz, d = 20.5, 21.3, 48.5, 63.6, Calcd for C8H18ClNO2: C,
1 H), 3.39–3.55 (br m, 7 H), 4.13–4.18 (m, J = 4.4, 4.8, 5.2 Hz, 65.5, 65.8, 66.7
49.10; H, 9.27. Found: C, 48.99;
H, 9.41
1 H)
D1
E1
d = 1.32 (br m, J = 6.4 Hz, 4 H), 1.69 (br m, J = 5.2, 6.4 Hz, 4 H), d = 21.8, 25.0, 51.5, 51.7, Calcd for C16H38Cl2N2O4: C,
3.05 (s, 6 H), 3.06 (s, 6 H), 3.28–3.34 (m, 8 H), 3.46–3.48 (m,
63.6, 65.3, 65.6, 66.1
48.85; H, 9.74. Found: C, 48.48;
H, 9.54
J = 2.4, 2.8 Hz, 4 H), 4.15 (m, J = 4.6, 6.8 Hz, 2 H)
d = 2.33 (m, 2 H), 3.17 (s, 6 H), 3.19 (s, 6 H), 3.44–3.54 (br m, d = 16.9, 51.9, 52.1, 61.2,
12 H), 4.25 (m, 2 H) 61.4, 63.6, 66.0, 66.2
–
Table 2 31P NMR Spectroscopic Data for the Phosphate and Diphe-
nyl Phosphate Salts
Table 5 Thermochemical Properties of the Hydroxy Ammonium
Saltsa
Compound 31P NMR data (162 MHz, D2O)
Compound Water content
Mp (°C)
Tg (°C) Tdcp (°C)
A2
B2
C2
D2
A5
B5
C5
D5
d = 0.07 (s)
d = 0.10 (s)
d = 0.07 (s)
d = 0.10 (s)
d = –8.74 (s)
d = –8.96 (s)
d = –8.95 (s)
d = –8.88 (s)
A1
A2
A4
A5
B1
B2
B3
B4
B5
C1
C2
C4
C5
D1
D2
D3
D4
D5
E1
E3
F3
–
137–141
–
–
–
125–130
–
–
0.411%
–
–26
–
174
252
–
–
–
139–141
204–207
–
116–118
–
–
404 ppm
49.1
–33
–
403
–
–
105–106
–
93
–
282
277
–
Table 3 13C NMR Spectroscopic Data for the Bis(trifluoromethyl-
sulfonyl)imide Salts
–
105
–
Compound 13C NMR data (100.6 MHz, DMSO-d6)
–
90
–
206 ppm
–
–68
–28
–
220
274
–
B3
D3
E3
F3
d = 39.3, 59.3, 62.4, 70.6, 107.4, 114.5, 117.6, 120.8,
124.0, 141.9, 156.5
0.175%
–
d = 21.5, 25.2, 51.1, 51.2, 63.7, 64.0, 66.0, 114.6,
117.8, 121.0, 124.2
–
161–163
–
170
–
–
d = 16.4, 51.3, 60.7, 63.6, 65.9, 66.5, 114.6, 117.8,
121.0, 124.2
443 ppm
–
–34
–50
–5.1
–
363
222
233
–
d = 13.2, 13.3, 13.4, 48.7, 51.4, 51.5, 61.2, 63.6, 65.2,
65.9, 66.2, 114.6, 117.8, 121.0, 124.2
0.220%
–
–
–
–
–
–
Table 4 13C NMR Spectroscopic Data for the Dicyanamide Salts
112–115
Compound 13C NMR data (100.6 MHz, D2O)
–
–
–24
–16
–
A4
B4
C4
D4
E4
d = 44.2, 53.3, 63.6, 65.2, 66.7, 120.0
–
a Tg = glass transition, Tdcp = onset of decomposition temperature.
d = 39.4, 59.4, 62.4, 70.6, 107.4, 120.0, 141.9, 156.4
d = 20.6, 21.5, 48.6, 63.7, 65.6, 65.9, 66.6, 66.8, 119.9
d = 21.9, 25.1, 51.5, 51.7, 63.6, 65.4, 65.6, 66.1, 120.0
d = 16.8, 51.8, 52.0, 61.1, 61.3, 63.5, 65.8, 66.0, 66.1,
120.0
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

1442
M. Thomas et al.
PAPER
1H NMR (400 MHz, D2O): d = 3.07 (s, 6 H), 3.48–3.51 (m, 2 H),
3.92–3.95 (m, 2 H), 4.17–4.20 (br m, 1 H), 6.75 (d, J = 8.0 Hz, 2 H),
7.84 (d, J = 8.0 Hz, 2 H).
Table 6 Melting Points and Specific Rotations for the Chiral
DMAP Derivatives
25
Compound
B1
Mp (°C)
[a]589
–
1-(2,3-Dihydroxypropyl)-1-methylpyrrolidinium Chloride (C1)
1-Methylpyrrolidine (25.02 g, 0.29 mol) was dissolved in MeCN
(140 mL). Then, 3-chloropropane-1,2-diol (32.5 g, 0.29 mol) was
added. The reaction mixture was allowed to reflux at 65 °C for 24
h. The solvent was removed by rotary evaporation under high vac-
uum, and the remaining liquid was dried under high vacuum. This
resulted in the formation of a brown crystalline solid, which was
washed repeatedly with MeCN until it was white. The solid was
dried under high vacuum; yield: 36.8 g (64%).
204–207
(S)-(–)-B1
(R)-(+)-B1
B3
164.7
–100
164.2
+112.5
–
49.1 (–33, glass transition)
–32.9 (glass transition)
(S)-(–)-B3
–22.4
4,4,11,11-Tetramethyl-4,11-diazoniatetradecane-1,2,13,14-
tetrol Dichloride (D1)
All chemicals used in syntheses, purification, and comparison anal-
yses were of commercial reagent quality and were used without fur-
ther purification. All NMR measurements were performed on a
Bruker 400 MHz DPX400 instrument in D2O at r.t. Optical rotation
data were measured using a Ruudolph Autopol III instrument oper-
ating at 589 nm with samples dissolved in water. These measure-
ments were performed at Queens college, CUNY.
N,N,N¢,N¢-Tetramethylhexane-1,6-diamine (7.50 g, 0.044 mol) was
dissolved in 95% EtOH (40 mL). To this was added 3-chloropro-
pane-1,2-diol (10.0 g, 0.090 mol, 2 equiv). The reaction mixture
was refluxed at 65 °C for 24 h. The solvent was removed by rotary
evaporation leaving a white solid. The solid was washed with hex-
anes and dried under reduced pressure; yield: 16.56 g (94%).
DSC data were collected using a Q100 Differential Scanning Calo-
rimeter (TA Instruments). The scan rate was 5 degrees Celsius/min.
Thermal degradation data were collected using a Q500 Thermo-
gravimetric Analyzer (TGA, TA Instruments). The scan rate was
10 degrees Celsius/min. Onset decomposition temperatures were
determined using the Universal Analysis 2000 Software provided
by TA Instruments. Water content was determined using the TGA
or a Mettler Toledo DL39 Karl Fischer Coulometer. These instru-
ments were used at Brookhave National Laboratory, Upton, New
York. Elemental analyses were performed by Schwarzkopf Mi-
croanalytical Laboratory, Woodside, New York.
4,4,8,8-Tetramethyl-4,8-diazoniaundecane-1,2,10,11-tetrol
Dichloride (E1)
N,N,N¢,N¢-Tetramethylpropane-1,3-diamine (5.0 g, 0.038 mol) was
dissolved in a 4:1 soln of MeCN–EtOH (25 mL). To this, 3-chloro-
propane-1,2-diol (8.58 g, 0.078 mol) was added. The reaction mix-
ture was refluxed at 65 °C for 24 h, and the solvent was removed by
rotary evaporation under reduced pressure. The resulting viscous
liquid was dissolved in EtOH (25 mL), and Et2O (50 mL) was added
to precipitate the product. The solvent was decanted and the still vis-
cous, white liquid was dried under high vacuum. The resulting
white solid was washed with EtOAc and dried again under high vac-
uum; yield: 11.7 g (88%).
Synthesis of the Halide Salts
4,4,5,8,8-Pentamethyl-4,8-diazoniaundecane-1,2,10,11-tetrol
Dichloride (F1)
1-(2,3-Dihydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane
Chloride (A1)
N,N,N¢,N¢-Tetramethylbutane-1,3-diamine (5.0 g, 0.035 mol) was
dissolved in a 4:1 soln of MeCN–EtOH (25 mL). To this, 3-chloro-
propane-1,2-diol (8.48 g, 0.077 mol) was added. The reaction mix-
ture was refluxed at 65 °C for 24 h, and the solvent was removed by
rotary evaporation under reduced pressure. The resulting viscous
liquid was dissolved in EtOH (25 mL), and Et2O (50 mL) was added
to precipitate the product. The solvent was decanted and the clear,
yellow viscous liquid was dried under high vacuum. (The product
contained excess 3-chloropropane-1,2-diol.)
DABCO (9.98 g, 0.089 mol) was dissolved in EtOAc (65 mL). To
this, 3-chloropropane-1,2-diol (9.68 g, 0.088 mol) was added. The
reaction mixture was stirred for 24 h. The solvent was removed by
rotary evaporation under reduced pressure. The resulting solid was
stirred with MeCN (50 mL) for 24 h. The solid was collected by fil-
tration, washed with Et2O (3 × 30 mL), and dried under high vacu-
um to give A1 as a white solid; yield: 14.3 g (73%).
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium Chlo-
ride (B1)
Synthesis of the Phosphate Salts
DMAP (21.78 g, 0.18 mol) was dissolved in MeCN (150 mL). To
this was added 3-chloropropane-1,2-diol (19.71 g, 0.18 mol) and the
reaction mixture was stirred and refluxed at 65 °C for 24 h. This re-
sulted in a precipitate, which was collected by gravity filtration and
washed with EtOAc (3 × 30 mL) and Et2O (3 × 30 mL). The solid
was dried under high vacuum to give B1 as a white solid; yield:
40.78 g (97%).
1-(2,3-Dihydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane
Phosphate (A2)
Chloride salt A1 (7.62 g, 0.034 mol) was dissolved in MeOH (40
mL). To this, an excess of 98% H3PO4 (0.60 g) was added. The re-
action mixture was stirred for 24 h. A white precipitate was filtered
off and the solvent was evaporated. The resulting pale yellow solid
was dried in a high-vacuum oven; yield: 3.92 g (41%).
(S)-(–)-1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridini-
um Chloride [(S)-(–)-B1]
This salt was made following the procedure described for B1 above,
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium Phos-
phate (B2)
using (R)-(–)-3-chloropropane-1,2-diol; yield: 96%.
Chloride salt B1 (2.08 g, 0.009 mol) was dissolved in MeOH (35
mL). To this was added a charge equivalent amount plus 2% excess
of 98% H3PO4 (0.38 g, 0.004 mol). The reaction mixture was stirred
for 24 h. The solvent was removed by rotary evaporation under re-
duced pressure. The resulting white solid was recrystallized (abs
EtOH) and dried under high vacuum; yield: 1.94 g (74%).
(R)-(+)-1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridini-
um Chloride [(R)-(+)-B1]
This salt was made following the procedure described for B1 above,
using (S)-(+)-3-chloropropane-1,2-diol; yield: 95%.
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

PAPER
Synthesis and Thermochemical Properties of Hydroxy Ammonium Salts
1443
1-(2,3-Dihydroxypropyl)-1-methylpyrrolidinium Phosphate
(C2)
(50 mL). To this was added a charge equivalent amount of lithium
bis(trifluoromethylsulfonyl)imide (9.0 g, 0.031 mol). The reaction
mixture was stirred for 24 h. The solvent was carefully decanted and
the remaining liquid was washed with H2O until there was no de-
tectable halide (50 mM aq AgNO3 was used to test the wash). The
resulting liquid (6.0 g) was dried under high vacuum.
Chloride salt C1 (4.96 g, 0.027 mol) was dissolved in 95% EtOH
(50 mL). To this was added a charge equivalent amount of 98%
H3PO4 (1.2 g). The reaction mixture was stirred for 24 h. The sol-
vent was removed by rotary evaporation under reduced pressure.
The resulting viscous white solid was dried under high vacuum;
yield: 5.0 g (96%).
Synthesis of the Dicyanamide Salts
Tris-(4,4,11,11-Tetramethyl-4,11-diazoniatetradecane-
1,2,13,14-tetrol) Diphosphate (D2)
1-(2,3-Dihydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane
Dicyanamide (A4)
Chloride salt D1 (7.0 g, 0.018 mol) was dissolved in MeOH (50
mL). To this, a charge equivalent amount of 85% H3PO4 (1.0 g) was
added. The reaction mixture was stirred for 24 h. The solvent was
removed by rotary evaporation under reduced pressure, leaving be-
hind a white solid. The solid was recrystallized (EtOH) and dried
under high vacuum; yield: 3.5 g (50%).
Chloride salt A1 (8.20 g, 0.037 mol) was dissolved in distilled H2O
(25 mL). To this, a charge equivalent amount of AgN(CN)2 was
added. The reaction flask was covered with aluminum foil and the
reaction mixture was stirred for 24 h. The resulting solid was gravity
filtered and the filtrate was washed with Et2O (3 × 30 mL), hexanes
(3 × 30 mL), and EtOAc (3 × 30 mL). The water was then evaporat-
ed and the resulting viscous liquid was dried in a high-vacuum oven
to give A4 as a viscous brown liquid at r.t.; yield: 7.51 g (80%).
Synthesis of the Bis(trifluoromethylsulfonyl)imide Salts
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium
Bis(trifluoromethylsulfonyl)imide (B3)
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium Dicy-
anamide (B4)
Chloride salt B1 (6.0 g, 0.025 mol) was dissolved in distilled H2O
(50 mL). To this was added a charge equivalent amount of lithium
bis(trifluoromethylsulfonyl)imide (7.25 g, 0.025 mol). The reaction
mixture was stirred for 24 h. The solvent was carefully decanted and
the remaining liquid was washed with H2O until there was no de-
tectable halide (50 mM aq AgNO3 was used to test the wash). The
resulting low-melting solid was dried under high vacuum; yield:
3.54 g (30%).
Chloride salt B1 (2.14 g, 0.009 mol) was dissolved in distilled H2O
(25 mL). To this was added a charge equivalent amount plus 2% ex-
cess of AgN(CN)2. The reaction flask was covered with aluminum
foil and the reaction mixture was stirred for 24 h. The resulting pre-
cipitate was gravity filtered and the filtrate was washed with Et2O
(3 × 30 mL) and hexanes (3 × 30 mL). The aqueous solvent was re-
moved by rotary evaporation under reduced pressure. The resulting
pale yellow solid was dried under high vacuum; yield: 1.6 g (66%).
(S)-(–)-1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridini-
um Bis(trifluoromethylsulfonyl)imide [(S)-(–)-B3]
This salt was prepared from chloride (R)-(–)-B1 following the pro-
cedure described for B3 above; yield: 50%.
1H NMR (400 MHz, DMSO-d6): d = 3.14 (s, 6 H), 3.25–3.30 (dd,
J = 4.4, 6.4 Hz, 1 H), 3.42–3.46 (dd, J = 4.8, 5.2 Hz, 1 H), 3.70–3.80
(br m, 1 H), 4.04–4.09 (dd, J = 5.6, 8.0 Hz, 1 H), 4.30–4.34 (dd,
J = 2.8, 10.8 Hz, 1 H), 4.95 (br, 1 H), 5.30 (br, 1 H), 7.00 (d, J = 7.6
Hz, 2 H), 8.17 (d, J = 7.6 Hz, 2 H).
1-(2,3-Dihydroxypropyl)-1-methylpyrrolidinium Dicyanamide
(C4)
Chloride salt C1 (5.0 g, 0.025 mol) was dissolved in distilled H2O
(25 mL). To this was added a charge equivalent amount plus 2% ex-
cess of AgN(CN)2. The reaction flask was covered with aluminum
foil and the reaction mixture was stirred for 24 h. The resulting sil-
ver halide salt was gravity filtered and the filtrate was washed with
Et2O (3 × 30 mL) and hexanes (3 × 30 mL). The aqueous solvent
was removed by rotary evaporation under reduced pressure to give
a yellow liquid; yield: 4.5 g (80%).
4,4,11,11-Tetramethyl-4,11-diazoniatetradecane-1,2,13,14-
tetrol Bis[bis(trifluoromethylsulfonyl)imide] (D3)
4,4,11,11-Tetramethyl-4,11-diazoniatetradecane-1,2,13,14-
tetrol Bis(dicyanamide) (D4)
Chloride salt D1 (10.10 g, 0.026 mol) was dissolved in distilled H2O
(50 mL). To this was added a charge equivalent amount of lithium
bis(trifluoromethylsulfonyl)imide (14.93 g, 0.052 mol). The reac-
tion mixture was stirred for 24 h. The solvent was carefully decant-
ed and the remaining liquid was washed with H2O until there was
no detectable halide (50 mM aq AgNO3 was used to test the wash).
The resulting pale yellow liquid was dried under high vacuum;
yield: 8.77 g (38%).
Chloride salt D1 (5.46 g, 0.014 mol) was dissolved in distilled H2O
(25 mL). To this was added a charge equivalent amount plus 2% ex-
cess of AgN(CN)2. The reaction flask was covered with aluminum
foil and the reaction mixture was stirred for 24 h. The resulting sil-
ver halide salt was gravity filtered and the filtrate was washed with
Et2O (3 × 30 mL) and hexanes (3 × 30 mL). The aqueous solvent
was removed by rotary evaporation under reduced pressure. The re-
sulting yellow liquid was dried under reduced pressure; yield: 4.45
g (70%).
4,4,8,8-Tetramethyl-4,8-diazoniaundecane-1,2,10,11-tetrol
Bis[bis(trifluoromethylsulfonyl)imide] (E3)
4,4,8,8-Tetramethyl-4,8-diazoniaundecane-1,2,10,11-tetrol
Bis(dicyanamide) (E4)
Chloride salt E1 (5.9 g, 0.017 mol) was dissolved in distilled H2O
(50 mL). To this was added a charge equivalent amount of lithium
bis(trifluoromethylsulfonyl)imide (9.7 g, 0.034 mol). The reaction
mixture was stirred for 24 h. The solvent was carefully decanted and
the remaining liquid was washed with H2O until there was no de-
tectable halide (50 mM aq AgNO3 was used to test the wash). The
resulting liquid was dried under high vacuum; yield: 0.71 g (5%).
Chloride salt E1 (5.8 g, 0.017 mol) was dissolved in distilled H2O
(25 mL). To this was added a charge equivalent amount plus 2% ex-
cess of AgN(CN)2. The reaction flask was covered with aluminum
foil and the reaction mixture was stirred for 24 h. The resulting sil-
ver halide salt was vacuum filtered. The aqueous solvent was re-
moved by rotary evaporation under reduced pressure. The resulting
yellow liquid was dried under high vacuum; yield: 4.9 g (70%).
4,4,5,8,8-Pentamethyl-4,8-diazoniaundecane-1,2,10,11-tetrol
Bis[bis(trifluoromethylsulfonyl)imide] (F3)
Chloride salt F1 (a mixture of product F1 and excess 3-chloropro-
pane-1,2-diol starting material, 5.0 g) was dissolved in distilled H2O
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York

1444
M. Thomas et al.
PAPER
Synthesis of the Diphenyl Phosphate Salts
References
(1) McIntosh, J. M. J. Chem. Educ. 1978, 55, 235.
(2) Cohen, J. I.; Traficante, L.; Schwartz, P. W.; Engel, R.
1-(2,3-Dihydroxypropyl)-4-aza-1-azoniabicyclo[2.2.2]octane
Diphenyl Phosphate (A5)
Tetrahedron Lett. 1998, 39, 8617.
Chloride salt A1 (2.1 g, 0.009 mol) was dissolved in abs EtOH
(50 mL). To this, a charge equivalent amount of diphenyl phosphate
(2.4 g, 0.009 mol) and KOH (0.5 g, 0.009 mol) were added. The re-
action mixture was stirred for about 3 d. The resulting solid (KCl)
was removed by gravity filtration. The solvent of the filtrate was re-
moved by rotary evaporation under reduced pressure, leaving a vis-
cous liquid, which later solidified. The solid was recrystallized (abs
EtOH), and the white solid was dried under high vacuum; yield: 1.5
g (38%).
(3) Demberelnyamba, D.; Kim, K.; Choi, S.; Park, S.; Lee, H.;
Kim, C.; Yoo, I. Bioorg. Med. Chem. 2004, 12, 853.
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Eds.; Wiley-VCH: Weinheim, 2003.
1-(2,3-Dihydroxypropyl)-4-(dimethylamino)pyridinium Diphe-
nyl Phosphate (B5)
Chloride salt B1 (2.08 g, 0.009 mol) was dissolved in abs EtOH (50
mL). To this were added a charge equivalent amount of diphenyl
phosphate (2.24 g, 0.009 mol) and KOH (0.51 g, 0.009 mol). The
reaction mixture was stirred for 24 h. The potassium salt was re-
moved by vacuum filtration and the solvent of the filtrate was evap-
orated. The resulting white solid was washed with Et2O (3 × 10 mL)
and dried under reduced pressure; yield: 3.3 g (83%).
(11) Holbrey, J. D.; Seddon, K. R. Clean Prod. Processes 1999,
1, 223.
(12) Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.;
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(13) Short, P. L. Chem. Eng. News 2006, 84 (17), 15.
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(16) Engel, R.; Lall-Ramnarine, S.; Coleman, D.; Thomas, M.
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(17) Lall, S.; Behaj, V.; Mancheno, D.; Casiano, R.; Thomas, M.;
Rikin, A.; Gaillard, J.; Raju, R.; Scumpia, A.; Castro, S.;
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1-(2,3-Dihydroxypropyl)-1-methylpyrrolidinium Diphenyl
Phosphate (C5)
Chloride salt C1 (2.0 g, 0.01 mol) was dissolved in abs EtOH
(50 mL). To this were added a charge equivalent amount of diphe-
nyl phosphate (2.6 g, 0.01 mol) and KOH (0.6 g, 0.01 mol). The re-
action mixture was stirred for 24 h. The potassium salt was removed
by vaccum filtration and the solvent of the filtrate was evaporated.
The resulting yellow liquid was dissolved in MeOH (50 mL) and
charcoal (5–10 mg) was added. The mixture was stirred for 24 h and
the charcoal was removed by gravity filtration. The liquid was then
passed through an alumina column. The solvent was evaporated and
the resulting pale yellow liquid was dried under reduced pressure;
yield: 1.9 g (47%).
(19) Bonhote, P.; Dians, P.; Papageorgio, N.; Kalyanasundaram,
K.; Gratzel, M. Inorg. Chem. 1996, 35, 1168.
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D. R.; Scott, J. L. Green Chem. 2006, 691.
4,4,11,11-Tetramethyl-4,11-diazoniatetradecane-1,2,13,14-
tetrol Bis(diphenyl phosphate) (D5)
Chloride salt D1 (5.0 g, 0.013 mol) was dissolved in MeOH (50 mL).
To this was added a charge equivalent amount of diphenyl phos-
phate (6.2 g, 0.025 mol). The reaction mixture was stirred for 24 h.
The solvent was evaporated and the resulting white solid was dried
under reduced pressure; yield: 10.1 g (95%).
(22) Huddleston, J. G.; Visser, A. E.; Reichert, M.; Willauer, H.
D.; Broker, G. A.; Rogers, R. D. Green Chem. 2001, 156.
Acknowledgment
We are grateful for the assistance of Dr. James Wishart and Dr.
Tomasz Szreder from Brookhaven National Laboratory (BNL), and
the Diversity Office at BNL, and for support from the Magnet Pro-
gram at The CUNY Graduate Center and NYC LSAMP.
Synthesis 2009, No. 9, 1437–1444 © Thieme Stuttgart · New York