Quaternary Ammonium-Supported Scavenger Reagents for Acids and Electrophiles

Article abstract of DOI:10.1002/ejoc.200300403

The present article describes how we devised new quaternary ammonium-supported quench reagents (TAMA-Cl and BAX-sulfate) for scavenging acids and excess electrophiles from crude reaction mixtures. TAMA-Cl is liquid at room temperature, but is very glutinous and has to be used in aqueous solution. It removes unchanged electrophiles very efficiently. An aqueous preparation of TAMA-Cl may be easily added in automated syntheses, and high-throughput phase-separation techniques shoud allow purification of scavening-containing reaction mixtures. However, workup with TAMA-Cl is more complex than simple filtration. Recognizing this major advantage of solid-phase syntheses, we designed BAX-sulfate, a highly crystalline scavenger reagent that allows reactions workup to be simplified to a single filtration and evaporation of solvent. BAX-sulfate reacts with electrophiles; quenches acids and precipitates quantitatively when diethyl ether is added. It even precipitates from methanol solutions. With BAX-sulfate the workup stage uses simple filtration to make crude separations.

Full text of DOI:10.1002/ejoc.200300403

FULL PAPER
Quaternary Ammonium-Supported Scavenger Reagents for Acids and
Electrophiles
Noha Ghanem,[a] Jean Martinez,[a] and Didier Stien*[a]
Keywords: Amines / Scavenger reagents / Electrophiles trapping / Lewis acids
The present article describes how we devised new quater-
nary ammonium-supported quench reagents (TAMA-Cl and
BAX-sulfate) for scavenging acids and excess electrophiles
from crude reaction mixtures. TAMA-Cl is liquid at room
temperature, but is very glutinous and has to be used in
aqueous solution. It removes unchanged electrophiles very
efficiently. An aqueous preparation of TAMA-Cl may be
easily added in automated syntheses, and high-throughput
phase-separation techniques should allow purification of
scavenger-containing reaction mixtures. However, workup
nizing this major advantage of solid-phase syntheses, we de-
signed BAX-sulfate, a highly crystalline scavenger reagent
that allows reaction workup to be simplified to a single filtra-
tion and evaporation of solvent. BAX-sulfate reacts with elec-
trophiles, quenches acids and precipitates quantitatively
when diethyl ether is added. It even precipitates from meth-
anol solutions. With BAX-sulfate the workup stage uses
simple filtration to make crude separations.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
with TAMA-Cl is more complex than simple filtration. Recog- Germany, 2004)
Introduction
with good swelling properties such as DMF, dichlorometh-
ane, or THF.
To address these issues, several groups have developed
alternative nonpolymeric phase labels for quench re-
agents.[6] Some water-soluble[7] and some fluorous tag-
bound scavengers,[8,9] as well as a polyaromatic-supported
scavenger reagent[10] have been designed to circumvent
these limitations. More recently, Wilcox has described the
first photoactivable precipiton-supported isocyanate and
has demonstrated that it could be used successfully as a
selective scavenger reagent for amines.[11] Some 2-substi-
tuted-5-norbornenes have also been used to quench electro-
philes. A ring-opening metathesis polymerization applied to
the crude reaction mixture generates a polymer that can be
precipitated with specific solvents, leaving the desired prod-
ucts essentially pure.[12,13]
Our basic idea was to replace the polymeric core of poly-
styrene-supported dendrimer-like scavenger reagents[14] by
a specific functional group of low molecular weight. Using
this strategy, we hoped to build an efficient, very high-load-
ing scavenger reagent. This report describes the synthesis of
new quaternary ammonium salts bearing amino functional-
ities, and demonstrates how they can be used to remove
electrophiles.
Solid-phase organic synthesis is routinely used for the
preparation of combinatorial libraries of small organic mol-
ecules. The clear advantage of this biphasic method is in
the area of purification, as simple filtration generally leads
to the desired products in high purity. However, excess of
reagents is usually necessary to drive the reaction to com-
pletion and preparation of a target compound on a solid
support may require up to two additional steps compared
to the same synthesis in solution, one to anchor the starting
material to the resin bead and another to cleave the product
from the solid support.
Therefore, there has been concomitant growth of solu-
tion-phase preparations of chemical libraries.[1,2] Quench
reagents have been conceived so that in the development of
new technologies there is a reduced need for chromato-
graphic purifications.[3Ϫ5] These scavenger resins offer the
convenience of solution-phase reactions with the advan-
tages of solid-phase techniques. However, there is consider-
able scope for improvement. Most of these compounds are
reticulated polystyrene resins and the major drawbacks of
these supported scavengers are their high cost, the large
amount generally required to clean up a typical reaction
product and long reaction times arising from the solid/
liquid interface reactions. Moreover, these Merrifield-type
resins are hydrophobic and their use is restricted to solvents
Results and Discussion
Our synthesis of electrophile-scavenging quaternary
ammonium salt 3 employs methylation of Boc-protected
tris(2-aminoethyl)amine (1) (Boc ϭ tert-butoxycarbonyl)
(Scheme 1).[15] The progress of the methylation reaction was
[a]
´
LAPP-UMR CNRS 5810, Universites Montpellier 1&2,
Place E. Bataillon, CC19, 34095 Montpellier cedex 5, France
Fax: (internat.) ϩ 33-4-67144866
E-mail: stien@univ-montp2.fr
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DOI: 10.1002/ejoc.200300403
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Quaternary Ammonium-Supported Scavenger Reagents for Acids and Electrophiles
FULL PAPER
monitored by reversed-phase high-pressure liquid chroma- low molecular mass (196.7 g·molϪ1) and dense functionaliz-
tography. This reaction was completed within 3 d with a ation, 3 is to the best of our knowledge the highest loaded
four-fold excess of methyl iodide in a sealed reaction vessel. supported scavenger reagent known so far, bearing
This quaternary ammonium salt was purified by diluting 15.3 mmol of reactive amino groups per gram of com-
the crude reaction mixture with ethyl acetate and extracting pound.
with deionized water. It is interesting that, although triply
Boc-protected, this ammonium salt is hydrophilic enough
to be extracted by water from an organic solvent. The Boc
groups were subsequently removed using trifluoroacetic
acid (TFA), and after evaporation of excess reagent, the IϪ/
tris(trifluoroacetate) salt 2 was obtained in quantitative
yield in essentially pure form.
However, this quench reagent was difficult to manipulate
because of its high viscosity. Since we could reasonably ex-
pect it would be hygroscopic, we decided to use it in aque-
ous solution, and therefore dissolved it in water at a concen-
tration of 0.87 . We chose water because it does not evap-
orate easily, which implies that solution concentration
would be reliable over time. Furthermore, water is the
cheapest and safest solvent and although it is not miscible
with most organic solvents, amines dissolved in water are
known to react readily with electrophiles in organic phases.
Starting from benzylamine and indole, an array of am-
ides, carbamates, ureas, and sulfonamides was synthesized
using excess electrophiles (1.5 equiv.) and eventually tri-
ethylamine when required (Table 1, Entries 3 and 7). Sub-
sequent removal of the remaining electrophiles from solu-
tion using triamine 3 afforded the products in excellent
yields and purities.
Scheme 1
One equiv. of TAMA-Cl (i.e. 3 equiv. of amino groups)
Filtration through an anion-exchange resin (Amberlite per equivalent of excess electrophilic reagent was used to
IRA400, ClϪ form) allowed us to isolate the compound in trap the unchanged electrophile. Two different simple pro-
which counterions were quantitatively replaced by chloride cedures were attempted for removal of the quaternary am-
ions, as indicated by 13C NMR spectroscopy. The final monium-bound amino scavenger and its derivatives re-
stage of the scheme requires deprotonation of the terminal sulting from the trapping of excess electrophiles. First, we
ammonium salts. This was effected using sodium hydroxide, found that washing crude reaction mixtures with water af-
as insoluble sodium chloride formed in this reaction could forded the pure desired products in the organic layer
be easily separated from the desired product by trituration (Table 1, Method A). Secondly, we found that drying crude
with ethyl alcohol. Filtration and concentration of the fil- mixtures with sodium sulfate and filtering through a short
trate afforded the desired tris(2-aminoethyl)(methyl)am- pad of silica gel (solvent: EtOAc) also gave the expected
monium chloride (TAMA-Cl, 3) in pure form. Owing to its products electrophile-free in very high yields (Table 1,
Table 1. Electrophile trapping with TAMA-Cl and BAX-sulfate from crude reaction mixture
[a]
With TAMA-Cl: Method A (adding ethyl acetate and washing three times with water) or method B [drying with sodium sulfate and
filtering through a short pad of silica (solvent: EtOAc)] gave the same results. With BAX-sulfate: Method C [addition of diethyl ether
[b]
(CDCl3/Et2O, 1:1) and filtration] gave identical results in terms of purity. All yields are isolated yields of TAMA-Cl-purified material.
[c]
Yields with BAX-sulfate are identical within the uncertainty range. Purity was estimated at above 90% when no trace of side product
[d]
was detected by 1H NMR spectroscopy.
proportion of contaminant remaining.
Contaminated with a stearic acid derivative. Yield was not calculated because of the large
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N. Ghanem, J. Martinez, D. Stien
FULL PAPER
Method B). The two methods turned out to be equally ef- collected by filtration. Extraction with water or filtration
ficient. Purities were assumed to be above 90% when no though silica gel did provide the reaction product in pure
trace of side-products was detected by 1H NMR spec- form. However, it is clear that this quench reagent is no
troscopy. In most cases, no further purification was re- better than the previous one.
quired for organic synthesis purposes.
Only in one case (Table 1, Entry 5) was the resulting
amide still contaminated, probably with a stearate salt.
However, 1H NMR spectroscopy indicated that neither ste-
aric anhydride nor derivatives of TAMA-Cl were left, and
the rather polar contaminant was easily removed by chro-
matography. Entry 5 was the only example where further
purification was necessary. Since no residual carboxylate
was detected for acetic anhydride scavenging (Table 1, Entry
2), short-chain carboxylic acids may also be trapped by
Scheme 2
this triamine.
Such aqueous preparations of TAMA-Cl may be easily
added in automated syntheses, and high-throughput phase-
With the idea of building a scavenger reagent that would
separation techniques should allow purification of scaven- be more prone to precipitation and would be almost as
ger-containing reaction mixtures. However, reaction highly loaded as our first one, we decided to prepare the
workup is not as straightforward as simple filtration. larger and somewhat more rigid α,αЈ-bis{2-[bis(2-amino-
Recognizing this major advantage of solid-phase synthesis, ethyl)(methyl)ammonio]ethylamino}-p-xylene
dichloride
we set out to devise another scavenger reagent with which (BAX-2Cl; Scheme 3).
the reaction workup could be simplified to a single filtration
and evaporation of solvent.
Our synthesis involved grafting the tetraamine onto α,αЈ-
dichloro-p-xylene. The crude reaction mixture was Boc-pro-
In 1999, Perrier et al. described a new strategy to use tected, and purification afforded the desired branched hexa-
aromatic amines as support for solution-phase organic syn- carbamate 5 in 52% yield over two steps. After methylation,
thesis and found that protonation with sulfuric acid pro- the Boc protecting groups were removed using TFA, and
vided the best behaved solids.[16] On the basis of this work, after evaporation of excess reagent, the 2IϪ/hexakis(trifluo-
we considered using the divalent sulfate counterion instead roacetate) salt was obtained in excellent yield in pure form.
of ClϪ. Therefore, scavenger 3 was treated with a saturated The chloride form was obtained by anion exchange to fa-
aqueous solution of exactly 0.5 equiv. of silver sulfate cilitate purification after deprotonation, and treatment with
(Scheme 2). The amount of silver chloride formed suggested aqueous sodium hydroxide afforded the desired scavenger
that the exchange was quantitative. Insoluble silver chloride reagent. However, we found that this derivative did not
was removed by filtration, and lyophilization led to the ex- crystallize readily and we were only able to obtain it in solid
pected quench reagent 4 in quantitative yield. Although this form after careful purification by preparative reversed-
compound was indeed solid immediately after lyophiliz- phase high-pressure liquid chromatography. Recognizing
ation, it became sticky almost at once after being removed that synthesis of scavengers should be straightforward and
from vacuum. Attempts to use it as a scavenger reagent economically viable, we looked for alternative counterions.
demonstrated that its derivatives do separate from reaction Treatment with 0.5 equiv. of silver sulfate generated the cor-
mixtures when diethyl ether is added, but stay at the bottom responding BAX-sulfate (7), which was found to be highly
of the flask in the form of a sticky residue that cannot be crystalline and apparently not very hygroscopic.
Scheme 3
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Quaternary Ammonium-Supported Scavenger Reagents for Acids and Electrophiles
FULL PAPER
This derivative is only soluble in water and to a lesser Conclusion
extent in methanol. Its amino groups loading is 11.5
mmol·gϪ1. Like polymer-supported scavenger reagents, it
In summary, we have prepared two complementary
quaternary ammonium-supported polyamines (TAMA-Cl
and BAX-sulfate) which have found applications as high-
loading scavenger reagents for quenching acids and excess
of electrophiles from crude reaction mixtures. It is note-
worthy that in the case of scavengers the number of equiva-
lents should be calculated on a molar basis. As a result,
approximately one third to one quarter the weight of scav-
enger was required to achieve a scavenging efficiency similar
to high-loading commercially available resins (typically
loaded at about 3 mmol·gϪ1).
High-loading scavenger reagents offer the advantage of
producing less waste while facilitating product purifications.
Relative to traditional polymer-supported scavengers, these
ones use even less solvent, require less material, and elimin-
ate undesired contaminants equally well, even from meth-
anolic solutions, which is something that hydrophobic poly-
styrene-based resins cannot do. The workup stage uses sim-
ple phase-separation techniques such as extraction, fil-
tration and evaporation of solvent to make crude
separations.
reacts readily with electrophiles and acids at the solid/liquid
interface. In fact, its ability to remove excess of electrophiles
was first put to the test of purification of all the reaction
mixtures listed in Table 1. The same levels of purity, and
essentially the same yields, were obtained as with quench
reagent 3 dissolved in water. However, in this case the scav-
enger reagent and its derivatives were removed by simple
filtration after addition of diethyl ether to ensure quantitat-
ive precipitation (CDCl3/Et2O, 1:1).
An example of the application of BAX-sulfate in syn-
thesis is shown in Scheme 4. While working on a medicinal
chemistry project, we were interested in generating a solu-
tion-phase library of N-(chloroacetyl) N-substituted amino
acids. However, the reaction proceeded very slowly with 1
equiv. of electrophile and generally stopped at about 50%
conversion. Therefore, amine 8 and a three-fold excess of
anhydride were allowed to react for 2 h in dichloromethane.
The quaternary ammonium quenching agent was then ad-
ded to scavenge the excess anhydride (1 mol-equiv. relative
to the excess anhydride). The scavenging reaction was al-
lowed to proceed overnight at ambient temperature. Ad-
dition of diethyl ether ensured complete precipitation of
ionic species, which were removed by filtration. This simple
workup procedure gave the product in very high yield and
in excellent purity (Ͼ 90% by 1H NMR).[17] Indeed, we
were able to use this product without further purification
in the next step of our synthesis.
If BAX-sulfate was to be used in industry, the first step
of the synthesis would certainly need to be improved and
2Ϫ
ClϪ/SO4 exchange would have to be performed without
silver sulfate. However, based upon the success of these sim-
ple test examples, it seems reasonable to conceive of tra-
ditional solution-phase multistep syntheses with quaternary
ammonium-supported scavenger purifications. Thus, am-
monium-supported quenching could be applied to the prep-
aration of chemical libraries in solution.
Experimental Section
General Remarks: 1H NMR spectra were recorded at 200 or
300 MHz and 13C NMR spectra at 75.5 or 100.6 MHz as indicated.
Chemical shifts (δ) are in ppm downfield from tetramethylsilane,
and coupling constants (J) are in Hz; s, singlet; q, quadruplet; m,
multiplet. All solvents were dried and distilled by standard tech-
niques. Analytical HPLCs were run with a Nulceosil C18 column
(250 ϫ 4.6 mm). A polarity gradient water/acetonitrile (100:0 to
0:100) was applied for 20 min immediately after injection. Aceto-
nitrile and water contained 0.1% TFA. Detailed experimental pro-
cedures relating to synthesis and use of TAMA-Cl have been pub-
lished previously.[15]
Scheme 4
We then decided to test our new reagent for precipitation
from methanol. Known relative proportions of p-tolu-
enesulfonic acid and pentamethylbenzene as an NMR in-
ternal standard were combined in methanol. Quenching
with 0.5 equiv. of BAX-sulfate (3 equiv. of amino groups)
resulted in the formation of a cloudy solution. Dilution
with diethyl ether led to the formation of a well-behaved
precipitate that could be collected by filtration. Diethyl
ether was added for good measure to ensure that no traces
of scavenger derivatives remained in solution (diethyl ether/
Boc-Protected
α,αЈ-Bis{2-[bis(2-aminoethyl)amino]ethylamino}-p-
xylene 5: 1,4-Bis(chloromethyl)benzene (1.0 g, 5.7 mmol) was ad-
ded to a solution of tris(2-aminoethyl)amine (5.1 mL, 34.2 mmol)
in dichloromethane (2 mL). The reaction mixture was stirred for
24 h at room temperature, then DMAP (70 mg, 0.57 mmol) and
Boc2O (24.6 g, 113 mmol) were added at 0 °C. The mixture was
warmed to room temperature, stirred for another 24 h, concen-
trated and then purified by column chromatography (hexane/
EtOAc, 6:4) to give 5 (2.95 g, 52% over two steps) as a colourless
oil. 1H NMR (CDCl3, 200 MHz, ppm): δ ϭ 1.45 (br. s, 54 H), 2.53
(br. s, 12 H), 3.14 (br. s, 8 H), 3.27 (br. s, 4 H), 4.43 (br. s, 4 H),
1
methanol, 1:1). Concentration of the filtrate and H NMR
spectroscopic analysis demonstrated that pentamethylben-
zene was isolated without any detectable trace of contami-
nant (i.e. pTsOϪ salts and derivatives of the scavenger re-
agent).
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N. Ghanem, J. Martinez, D. Stien
FULL PAPER
7.12 (br. s, 4 H). 13C NMR (CDCl3, 100.6 MHz, ppm): δ ϭ 14.6 35.0 (CH2), 40.7 (CH2), 49.6 (CH2), 52.4 (CH3), 60.4 (CH2), 62.7
(CH3), 21.5 (CH3), 28.9 (CH3), 38.9 (CH2), 45.1 (CH2), 45.4 (CH2), (CH2), 129.3 (CH), 138.4 (C) ppm. HRMS: calcd. for C22H48N8
50.9 (CH2), 52.4 (CH2), 53.0 (CH2), 53.8 (CH2), 54.2 (CH2), 60.8
(CH2), 79.4 (C), 80.6 (C), 127.8 (CH), 128.3 (CH), 137.8 (C), 156.4
(C), 156.7 (C), 171.6 (C). MS (FABϩ, GT matrix): m/z (%) ϭ 995
[MHϩ] (62), 895 (11), 447 (49). HRMS: calcd. for C50H90N8O12
m/z ϭ 995.6756 [MHϩ], found 995.6683.
m/z ϭ 212.2001 [M2ϩ/2], found 212.2018.
General Procedure for Electrophile Scavenging with BAX-Sulfate
(Table 1): The electrophile (1.5 equiv.) was added to a solution of
benzylamine or indole (1 equiv.) and triethylamine when needed
(Entries 3 and 7) in dichloromethane. At the end of the reaction
(typically 1 h), BAX-sulfate (0.25 equiv., 3 equiv. of amino groups
per excess electrophile) was added and the reaction mixture was
allowed to stand overnight at room temperature. Addition of di-
ethyl ether (diethyl ether/dichloromethane, 1:1), filtration, and
evaporation of the solvents allowed isolation of the desired prod-
ucts in excellent yields pure enough for organic chemistry purposes
(except with stearic anhydride as electrophile, Entry 5).
Boc-Protected BAX-2I: Methyl iodide (1.25 mL, 20 mmol) was ad-
ded to a solution of diamine 5 (5 g, 5.03 mmol) in acetonitrile
(10 mL). The reaction vessel was sealed. The progress of the reac-
tion was monitored by reversed-phase HPLC. After 3 d at room
temperature, HPLC showed complete disappearance of a peak at
tR ϭ 11.02 min and the emergence of a new signal at tR
ϭ
10.67 min. Concentration allowed isolation of the desired product
1
in pure form (6.38 g, quant.). H NMR (CDCl3, 200 MHz, ppm):
N-Benzyl-N-(α-chloroacetyl)phenylalanine Methyl Ester (9): α-
Chloroacetic anhydride (22.5 mg, 0.316 mmol) and triethylamine
(11 mL, 0.079 mmol) were successively added to a solution of N-
benzyl-phenylalanine methyl ester (21.2 mg, 0.079 mmol) in
CDCl3. HPLC indicated that the reaction was complete within 3
h. BAX-sulfate (120 mg, 0.237 mmol) was then added and the reac-
tion mixture was stirred overnight at room temperature. Diethyl
ether (1 mL) was added, the reaction mixture was filtered, and the
precipitate was washed with more diethyl ether (2 ϫ 1 mL). Con-
centration provided the desired product containing no detectable
trace of either α-chloroacetic anhydride derivatives or BAX-sulfate
derivatives (24 mg, 87%). 1H and 13C NMR spectra are identical
to those previously described in the literature.[17]
δ ϭ 1.39 (br. s, 54 H), 3.28 (br. s, 6 H), 3.61 (m, 24 H), 4.85 (br. s,
4 H), 5.84 (br. s, 4 H), 7.29 (s, 4 H). 1H NMR ([D4]MeOH,
200 MHz, ppm): δ ϭ 1.47 (br. s, 54 H), 3.23 (s, 6 H), 3.51 (br. s,
20 H), 3.80 (br. s, 4 H), 4.55 (s, 4 H), 7.37 (s, 4 H). 13C NMR
([D4]MeOH, 100.6 MHz, ppm): δ ϭ 22.7 and 27.7 (CH3), 34.2
(CH2), 40.5 and 40.9 (CH2), 49.2 (CH3), 50.2 and 51.1 (CH2), 58.8
and 59.2 (CH2), 61.0 (CH2), 80.0 (C), 81.5 and 82.1 (C), 128.0 and
128.3 (CH), 137.5 (C), 155.8 and 156.1 (C), 157.1 (C).
BAX-2I·6TFA (6): Boc-protected BAX-2I (6.38 g, 4.99 mmol) was
treated with 50% TFA in dichloromethane (10 mL) for 2 h. Solvent
and excess reagent were then removed under reduced pressure to
give the desired product in pure form (6.80 g, 100%). 1H NMR
(D2O, 200 MHz, ppm): δ ϭ 2.96 (s, 6 H), 3.22Ϫ3.50 (m, 18 H),
3.91 (s, 4 H), 7.05 (s, 4 H). 13C NMR (D2O, 100.6 MHz, ppm): δ ϭ
32.2 (CH2), 39.6 (CH2), 49.6 (CH3), 52.5 (CH2), 57.2 (CH2), 58.3
(CH2), 116.0 (q, J ϭ 291 Hz, C), 130.7 (CH), 131.5 (C) 162.4 (q,
J ϭ 36 Hz, C).
Quenching of TsOH in Methanol: p-Toluenesulfonic acid
monohydrate (38.2 mg, 0.20 mmol) and pentamethylbenzene
(20 mg, 0.134 mmol) were dissolved in deuterated methanol
(1 mL). BAX-sulfate (53 mg, 0.10 mmol, 0.75 equiv./1 equiv.TsOH)
was added. After 1 h of stirring at room temperature, diethyl ether
(1 mL) was added and the precipitate was removed by filtration
and washed with more diethyl ether (3 mL). After concentration,
1H NMR spectroscopy indicated that TsOH had been quantitat-
ively sequestered by BAX-sulfate.
BAX-2Cl·6HCl: BAX-2I.6TFA (6) (6.80 g, 4.99 mmol) was dis-
solved in distilled water (20 mL) and loaded onto a column of
Amberlite IRA 400 (13 g, 3.8 mequiv. ClϪ/g, 50 mmol). The col-
umn was eluted very slowly with water. The collected aqueous
phase was concentrated by rotary evaporation then lyophilized to
give the desired octaammonium salt (3.08 g, 86%). 1H NMR (D2O,
200 MHz, ppm): δ ϭ 3.37 (s, 6 H), 3.56Ϫ3.64 (m, 8 H), 3.70Ϫ3.92
(m, 16 H), 4.34 (s, 4 H), 7.53 (s, 4 H). 13C NMR (D2O, 75.5 MHz,
ppm): δ ϭ 32.6 (CH2), 39.9 (CH2), 50.0 (CH3), 51.4 (CH2), 57.4
(CH2), 58.5 (CH2), 131.0 (CH), 131.7 (C).
Acknowledgments
The authors gratefully acknowledge Dr. Florine Cavelier for help-
ful discussions and pertinent remarks.
BAX-2Cl: A solution of sodium hydroxide (1.22 g, 30.6 mmol) in
distilled water (5 mL) was added to BAX-2Cl·6HCl (3.57 g,
5.11 mmol). After concentration, the residue was triturated with
ethanol and insoluble sodium chloride was removed by filtration.
The filtrate was concentrated to give the desired product (2.32 g,
93%) as a viscous pale-yellow oil. 1H NMR ([D4]MeOH, 200 MHz,
ppm): δ ϭ 3.03Ϫ3.13 (m, 12 H), 3.20 (s, 6 H), 3.38Ϫ3.54 (m, 12
H), 3.82 (s, 4 H), 7.38 (s, 4 H). 13C NMR ([D4]MeOH, 75.5 MHz,
ppm): δ ϭ 34.8 (CH2), 42.0 (CH2), 49.2 (CH3), 52.7 (CH2), 61.4
(CH2), 63.6 (CH2), 128.3 (CH), 138.6 (C).
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Quaternary Ammonium-Supported Scavenger Reagents for Acids and Electrophiles
FULL PAPER
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