Sodium borohydride-mediated transesterification

Article abstract of DOI:10.1080/00397910903072438

In the presence of sodium borohydride, esters react with alcohols with formation of the corresponding esters. The reaction is sensitive to the solvent, structure of the ester, and is often concurrent with reduction. Thioesters containing an ester group can be selectively cleaved by the reagent. Both esters and thioesters attached to solid support are resistant toward sodium borohydride. The in situ prepared sodium tetraalkoxyborate is introduced as an efficient reagent and catalyst for transesterification.

Full text of DOI:10.1080/00397910903072438

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Sodium Borohydride–Mediated
Transesterification
Grigoriy Sereda a , Swetha Pothula a & James Dreessen a
a University of South Dakota, Department of Chemistry, Vermillion,
South Dakota, USA
Version of record first published: 07 Apr 2010.
To cite this article: Grigoriy Sereda, Swetha Pothula & James Dreessen (2010): Sodium
Borohydride–Mediated Transesterification, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 40:9, 1312-1321
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Synthetic Communications1, 40: 1312–1321, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903072438
SODIUM BOROHYDRIDE–MEDIATED
TRANSESTERIFICATION
Grigoriy Sereda, Swetha Pothula, and James Dreessen
University of South Dakota, Department of Chemistry, Vermillion,
South Dakota, USA
In the presence of sodium borohydride, esters react with alcohols with formation of the
corresponding esters. The reaction is sensitive to the solvent, structure of the ester, and is
often concurrent with reduction. Thioesters containing an ester group can be selectively
cleaved by the reagent. Both esters and thioesters attached to solid support are resistant
toward sodium borohydride. The in situ prepared sodium tetraalkoxyborate is introduced
as an efficient reagent and catalyst for transesterification.
Keywords: Esterification; reduction; selectivity; synthesis; thioesters
INTRODUCTION
Synthesis of esters by transesterification is of significant interest for organic
synthesis[1] and is usually performed in the presence of a wide variety of catalysts.[2]
These procedures often require rather harsh conditions and therefore are not appli-
cable to acid- or base-sensitive substrates. Here we report that alcoholic sodium
borohydride, touted as unreactive toward esters, may substitute for the alcoholic
fragment in esters with a solvent-originated alkoxide group. This reaction has been
often overlooked because ethanolic sodium borohydride is a common reagent for
selective reduction of polyfunctional compounds with both the ethyl ester and the
oxo-groups. Alcoholic solutions of sodium borohydride are neither strongly acidic
nor basic, which makes the reagent convenient for transesterification of acid- and
base-labile esters.
RESULTS AND DISCUSSION
The reagent provides practical yields when reacted with methyl esters in etha-
nol. Thus, methyl benzoate 1 was converted by 0.5 equiv. of sodium borohydride to
ethyl benzoate 2 (73%) along with a small amount of benzyl alcohol 3 (11%) when
reacted for 24 h at room temperature (Table 1, entry 1; Scheme 1). Progress of the
reaction was monitored by NMR (singlet at 4.7 ppm, CH2-group of benzyl alcohol
Received March 26, 2009.
Address correspondence to Grigoriy Sereda, University of South Dakota, Department of
Chemistry, 414 E. Clark St., Vermillion, SD 57069, USA. E-mail: gsereda@usd.edu
1312

SODIUM BOROHYDRIDE–MEDIATED TRANSESTERIFICATION
1313
Table 1. Reaction of sodium borohydride with esters (reaction time 24 h)
Ester=
NaBH4
ratio
Starting
material
(%)
Product of
reesterification
(%)
Product of
reduction
(%)
Entry
Ester
Solvent
1
2
PhCO2Me, 1
PhCO2Me, 1
PhCO2Me, 1
95% EtOH
95% EtOH
abs. EtOH
95% EtOH
95% EtOH
95% EtOH
95% EtOH
i-PrOH
2:1
1:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
7
0
73
57
67
0
11
29
10
0
3
23
90
64
0.7
93
92
94
10
94
90
4
4-H2NPhCO2Me, 4
2-H2NPhCO2Me, 5
4-O2NPhCO2Me, 7
PhCO2C4H9-n, 10
PhCO2Me, 1
5
16
74
0
0
6
12
0
7
8
7
1
9
PhCO2Me, 1
DMF
0
0
10
11
12
n-C7H15CO2Me, 12
n-C7H15CO2Me, 12
Diester 13
abs. EtOH
i-PrOH
95% EtOH
64
0
7
0
0
0
3[5], and quadruplet at 4.35 ppm, CH2-group of ethyl benzoate 2[6]). Increasing the
ratio of sodium borohydride=ester to 1:1 favors reduction and thus lowers the yield
of transesterification to 57% (Table 1, entry 2). The reaction is moderately sensitive
to the presence of water in the solvent. In 95% ethanol, the reaction product con-
tained only 9–14% of benzoic acid, due to hydrolysis. In absolute ethanol, the reac-
tion was not accompanied with hydrolysis but proceeded more slowly and with less
selectivity of transesterification vs. reduction (Table 1, entry 3).
Both reduction and reesterification are completely suppressed by the electron-
donating 4-amino group in the benzene ring (Table 1, entry 4), probably because of
increased conjugation with the carbonyl group, stabilizing the starting material. The
2-amino isomer 5 is also significantly less reactive than methyl benzoate 1, but the
reaction does take place and produces exclusively the product of transesterification
(ethyl 2-aminobenzoate 6[7]) at 16% yield. In the latter case, the reaction was not
completely suppressed, probably because of coordination of the reagent with the
amino group, which increases the entropy of the step of nucleophilic attack. Interest-
ingly, both reactivity and selectivity of methyl 4-nitrobenzoate 7 (Table 1, entry 6)
are similar to those of the unsubstituted ester 1. No product of reduction of the
nitro-group was detected along with the products of transesterification 8[8] and ester
reduction 9.[9]
As opposed to methyl esters, butyl benzoate 10 was not reactive (Table 1,
entry 7), probably due to the steric hindrance at the alkoxy-leaving group.
Scheme 1. Reaction of methyl benzoate with NaBH4 in ethanol.

1314
G. SEREDA, S. POTHULA, AND J. DREESSEN
Both reduction and borohydride-mediated alcoholysis are strongly affected by
the solvent. Thus, methyl benzoate 1 undergoes alcoholysis (producing iso-propyl
benzoate 11[8]) and reduction in iso-propanol very slowly (Table 1, entry 8). It
remains unchanged in dimethylformamide (DMF; Table 1, entry 9). It is not surpris-
ing, considering the possibility of the hydride-to-alkoxy-ligand exchange in the boro-
hydride anion as a key step of transesterification. Methanol rapidly decomposes
sodium borohydride and thus proved to be an ineffective solvent.
We believe that the ligand exchange mechanism does not create significant
concentrations of free alkoxide anions, which makes the reaction significantly
different from the known fast (30-min) transesterification by the in situ–generated
secondary alkoxides.[9] It is known that tetraalkoxyborohydrides can be prepared
by the reaction of alkoxides with trialkoxyboranes, heavily shifted to the product,[10]
and the alkoxide exchange rate at boron in alcoholic solutions of alkoxyborohy-
drides is extremely slow.[11] However, we cannot completely rule out the intermedi-
acy of the alkoxide anions in the observed transesterification. The products of the
ligand exchange (full or partial) at boron can potentially act as transesterification
reagents. The synthetic potential of one of these complexes (tetraalkoxyborates)
was further explored in this study.
We found that in situ–prepared primary and secondary tetraalkoxyborates[12]
are efficient reagents for transesterification. Thus, a solution prepared by stirring
57 mg (1.5 mmol) of sodium borohydride, 2 ml of iso-propanol, and 0.5 ml
(6.8 mmol) of acetone for 30 min at room temperature quantitatively converted
0.1 ml (0.75 mmol) of methyl benzoate 1 to iso-propyl benzoate 11 for 24 h
(Scheme 2). Substitution of iso-propanol with ethanol and acetone with acetaldehyde
produced ethyl benzoate 2.
We found that the in situ–prepared tetraalkoxyborate reacts with methyl benzoate
in the absence of the alcohol solvent; however, the reaction rate decreases. Although the
transesterification performed in iso-propanol produced the ester 11 (95%) in 24h,
replacing the solvent with dimethylformamide (DMF) decreased the conversion to
63%. Besides the influence on the reaction rate, the alcohol solvent seems to rapidly
exchange alkoxy- groups with the borate complex under the reaction conditions. We
took advantage of this fact to increase the synthetic value of tetraalkoxyborates as trans-
esterification reagents. First, tetra(iso-propoxy)borate in ethanol converted methyl
benzoate 1 to ethyl benzoate 2 at an excellent yield (95%), which eliminated the need
for the aldehyde, corresponding to the alkoxide to be introduced into the ester molecule.
Scheme 2. Transesterification with tetraalkoxyborates.

SODIUM BOROHYDRIDE–MEDIATED TRANSESTERIFICATION
1315
Further, in situ–prepared tetra(iso-propoxy)borate from acetone in ethanol still
afforded the target ethyl ester 2 at 92%, which simplified the procedure even more.
The treatment of methyl benzoate 1 with sodium tetraethoxyborate in iso-propanol
predominantly led to iso-propyl benzoate 11 along with ethyl benzoate 2 and starting
methyl benzoate 1 (molar ratio 1:0.15:0.03), which lends additional support to the active
participation of the solvent in the reaction course.
Because of the exchange of alkoxy-groups between the borate complex and
the solvent, tetraalkoxyborates can be used as mild transesterification catalysts
rather than stoichiometric reagents. Thus, reaction of the in situ–prepared sodium
tetra(iso-propoxy) borate with 11-fold molar excess of methyl benzoate 1 in ethanol
led to its 85% conversion to ethyl benzoate 2 in 24 h, which increased up to 93% after
another 24 h.
The optimal time for transesterification with tetraalkoxyborates was found to
be 24 h, with a half-conversion time of 4 h. Importantly, applicability of this reaction
is not limited to methyl esters. Thus, an equimolar mixture of ethyl benzoate 2 and
methyl benzoate 1 was completely converted to iso-propyl benzoate 11 by the in situ–
generated sodium tetra(iso-propoxy)borate.
The suggested sodium borohydride–mediated transesterification is also applicable
to aliphatic esters, which would have undergone Claisen condensation in the presence of
alkoxides. Reactivity and selectivity of methyl octanoate 12 (Table 1, entry 10) was
found to be similar to methyl benzoate 1. The major product of the reaction was ethyl
octanoate 13[13] along with a small amount (7%) of 1-octanol 14.[14] However, as
opposed to methyl benzoate 1, neither transesterification nor reduction of 12 took place
in iso-propanol (Table 1, entry 11). Similar to the bulkiness of the alkoxy-group, steric
hindrance in the acidic fragment of esters strongly affected their reactivity with sodium
borohydride. Thus, both carbomethoxy-groups of the significantly hindered bicyclic
diester 13[15] (Scheme 3) were inert toward sodium borohydride in ethanol (Table 1,
entry 12). Possible coordination of the reagent with the ether methoxy-group proved
to be insufficient to activate the substitution.
It is known that reduction of aliphatic S-thioesters (S-thioesters of aliphatic
acids) by sodium borohydride in ethanol is not accompanied by alcoholysis.[16,17]
The hydride ligand at the atom of boron is expected to be ‘‘softer’’ than its alkoxide
counterpart, which explains its greater affinity for the more polarizable thioester
group. Although reactivity of the ester group toward sodium borohydride is signifi-
cantly diminished in bulky iso-propanol and completely suppressed in tert-butanol,
we found that thioesters are efficiently reduced under these conditions. Thus, the
Scheme 3. Structure of bicyclic ester 13.

1316
G. SEREDA, S. POTHULA, AND J. DREESSEN
thioester group of methyl 11-acetylthioundecanoate 14[18] was selectively reduced
(78% of the product of reduction and 22% of the starting material; no alcoholysis
took place) by 8 equiv. of sodium borohydride in tert-butanol for 31 h. However,
reduction of 14 on air was accompanied by partial oxidation of the produced
mercaptoester 15[18] to the corresponding disulfide by air. The disulfide 16[19] was
converted back to the mercaptane 15 by the subsequent treatment with 1 equiv. of
tributylphosphine (a known reagent for cleavage of disulfides[20]) in 3 ml of chloro-
form and one drop of water for 10 min. The overall conversion of 14 to 15 was
66% (Scheme 4). The progress of these transformations was monitored by 1H
NMR (d 2.86 for CH2, connected to the acetylthio- group,[18] d 2.53 for CH2, con-
nected to the mecrapto-group,[18] and d 2.68 for CH2, connected to the disulfide
group[21]). Utilization of either abs. iso-propanol or abs. ethanol solvent instead of
tert-butanol led to significant ester hydrolysis (17–50%).
Sodium borohydride in DMF did not react with the thioester or the ester group
of 14, probably because of the strong solvation of the borohydride anion. Attempts
to cleave the compound 14 with the in situ–generated sodium tetra(iso-propoxy)
borate led to a mixture of unidentified products.
As opposed to its methyl ester, 11-acetylthioundecanoic acid 17[22] did not
undergo noticeable reduction by 8 equiv. of sodium borohydride either in tert-
butanol or in iso-propanol for up to 27 h. However, reduction in ethanol for 4 h
quantitatively led to 11-mercaptoundecanoic acid 18.[23] Therefore, formation of a
boronic carboxy-derivative completely suppressed the reaction in branched solvents.
Although aliphatic and aromatic esters have similar reactivity toward sodium
borohydride, reduction of aromatic thioesters seems to proceed slower than their
aliphatic counterparts. Thus, reduction of methyl 11-benzoylthioundecanoate 19 [pre-
pared by dicyclohexylcarbodiimide (DCC) esterification of 11-benzoylthioundecanoic
acid 20[24]] by 8 equiv. of sodium borohydride in tert-butanol led to 45% of thioester
cleavage (versus 78% for methyl 11-acetylthioundecanoate 14). This behavior supports
an increased contribution of the first reaction step (addition to the carbonyl group,
breaking its conjugation with the benzene ring) to the reduction of thioesters.
Interestingly, neither thioester reduction nor transesterification took place for
11-acetylthioundecanoic acid 17, covalently immobilized on filter paper[25] or Wang
resin via the ester linkage. No mercapto-groups on the surface were detected by the
Ellman’s reagent. To ensure appropriate swelling of the Wang resin conjugate, a 1:1
mixture of DMF and ethanol was selected as solvent for the attempted cleavage.
However, deprotection of the Wang resin conjugate by sodium borohydride in
Scheme 4. Selective reduction of the thioester group in compound 14.

SODIUM BOROHYDRIDE–MEDIATED TRANSESTERIFICATION
1317
ethanol did not take place either. Cleavage of the immobilized material from the
solid support by 50% trifluoroacetic acid in dichloromethane (DCM) produced only
the starting acid 17. We attribute the lack of reactivity to the steric hindrance at the
surface of a solid support. Therefore, sodium borohydride can be safely used for
solid-supported syntheses, leaving the ester and thioester fragments intact.
CONCLUSION
We introduced sodium borohydride in ethanol as a mild reagent for transesteri-
fication of methyl esters. Sodium borohydride in tert-butanol selectively cleaves
thioesters, leaving the ester functionality intact. Both reesterification of esters and
reduction of thioesters are highly sensitive to the solvent and steric hindrance at
the reaction center. Tetraalkoxyborates generated in situ proved to be less selective
but significantly more efficient reagents and catalysts for transesterification.
EXPERIMENTAL
Reagents and solvents were purchased from Aldrich and Acros Organics. Wang
resin was purchased from Chem Impex. NMR spectra were recorded on a Mercury-200
spectrometer with tetramethylsilane (TMS) as an internal reference. Thin-layer chro-
matography (TLC) was run on Silufol plates with an ultraviolet (UV) indicator.
Reaction of Esters with Sodium Borohydride in Alcohols
Sodium borohydride (19 mg, 0.5 mmol) and the corresponding ester were stir-
red in 1 ml of solvent in a closed vial at rt, treated with 5 ml of water, acidified with
1 M HCl, and extracted with ethyl acetate. The organic layer was dried over MgSO4,
1
evaporated in vacuum, and analyzed by H NMR.
iso-Propyl Benzoate 11
A solution, prepared by stirring 57 mg (1.5 mmol) of sodium borohydride, 3 ml
of iso-propanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at room temperature in
a closed vial, was stirred with 0.1 ml (0.79 mmol) of methyl benzoate 1 for 24 h at
room temperature, poured into 20 ml of 1 M HCl, and extracted with ether. The
organic layer was dried over MgSO4, filtered, and evaporated to yield 123 mg
(95%) of iso-propyl benzoate 11 as a colorless liquid, identical to the known[8]
1
compound by H-NMR.
Ethylbenzoate 2
A solution, prepared by stirring 57mg (1.5mmol) of sodium borohydride, 3 ml of
ethanol, and 0.5 ml (0.90mmol) of acetaldehyde (added dropwise at cooling with ice) for
30min at rt in a closed vial, was stirred with 0.1 ml (0.79mmol) of methyl benzoate 1 for
24h at rt, poured into 20ml of 1 M HCl, and extracted with ether. The organic layer was
dried over MgSO4, filtered, and evaporated to yield 113 mg (95%) of ethyl benzoate 2 as
a colorless liquid, identical to the known[6] compound by 1H NMR.

1318
G. SEREDA, S. POTHULA, AND J. DREESSEN
Transesterification of Methyl Benzoate 1 in DMF
A solution, prepared by stirring 57 mg (1.5 mmol) sodium borohydride, 3 ml of
iso-propanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at room temperature in a
closed vial, was evaporated in vacuum to dryness. The residue was stirred with 3 ml
of DMF and 0.13 ml (1.03 mmol) of methyl benzoate 1 for 24 h at rt, poured into
20 ml of 1 M HCl, and extracted with ether. The organic layer was dried over
MgSO4, filtered, and evaporated to yield 151 mg of a colorless liquid, which con-
sisted (by 1H NMR) of iso-propyl benzoate 11 (63% yield) and starting 1 (32% yield).
Synthesis of Ethyl Benzoate 2 Without the Use of Acetaldehyde
A solution, prepared by stirring 57 mg (1.5 mmol) sodium borohydride, 3 ml of
iso-propanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at rt in a closed vial, was
evaporated in vacuum to dryness. The residue was stirred with 3 ml of abs. ethanol
and 0.1 ml (0.79 mmol) of methyl benzoate 1 for 24 h at rt, poured into 20 ml of 1 M
HCl, and extracted with ether. The organic layer was dried over MgSO4, filtered, and
evaporated to yield 113 mg (95%) of ethyl benzoate 2 as a colorless liquid.
Synthesis of Ethyl Benzoate 2 by the In Situ–Prepared Sodium
Tetra(iso-propoxy)borate
A solution, prepared by stirring 57 mg (1.5 mmol) of sodium borohydride, 3 ml
of ethanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at rt in a closed vial, was
stirred with 0.1 ml (0.79 mmol) of methyl benzoate 1 for 24 h at rt, poured into
20 ml of 1 M HCl, and extracted with ether. The organic layer was dried over
MgSO4, filtered, and evaporated to yield 110 mg (92%) of ethyl benzoate 2 as a
colorless liquid.
Synthesis of iso-Propyl Benzoate 11 with Sodium
Tetraethoxyborate in iso-Propanol
A solution, prepared by stirring 57 mg (1.5 mmol) sodium borohydride, 3 ml of
ethanol, and 0.5 ml (0.90 mmol) of acetaldehyde (was added dropwise at cooling with
ice) for 30 min at rt in a closed vial, was evaporated in vacuum to dryness. The resi-
due was stirred with 3 ml of iso-propanol and 0.1 ml (0.79 mmol) of methyl benzoate
1 for 24 h at rt, poured into 20 ml of 1 M HCl, and extracted with ether. The organic
layer was dried over MgSO4, filtered, and evaporated to yield 132 mg of a colorless
1
liquid, which consisted (by H NMR) of iso-propyl benzoate 11, ethyl benzoate 2,
and starting methyl benzoate 1 in the molar ratio of 1:0.15:0.03.
Tetraalkoxyborate-Catalyzed Transesterification of
Methyl Benzoate 1
A solution, prepared by stirring 57 mg (1.5 mmol) of sodium borohydride,
30 ml of ethanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at rt in a closed flask,
was stirred with 2 ml (16 mmol) of methyl benzoate 1 for 24 h at rt. A 3-ml sample of

SODIUM BOROHYDRIDE–MEDIATED TRANSESTERIFICATION
1319
the reaction mixture was poured into 20 ml of 1 M HCl and extracted with ether. The
organic layer was dried over MgSO4, filtered, and evaporated to yield 195 mg of a
1
colorless liquid, which consisted (by H NMR) of ethyl benzoate 2 and starting
methyl benzoate 1 in the molar ratio of 1:0.18 (85% conversion). NMR analysis of
a sample taken after another 24 h showed 93% conversion.
Full Transesterification of a 1:1 Mixture of Ethyl Benzoate 2 and
Methyl Benzoate 1
A solution, prepared by stirring 57 mg (1.5 mmol) of sodium borohydride, 3 ml
of iso-propanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at rt in a closed vial, was
stirred with 123 mg of a 1:1 mixture of ethyl benzoate 2 and methyl benzoate 1 for
24 h at rt, poured into 20 ml of 1 M HCl, and extracted with ether. The organic layer
was dried over MgSO4, filtered, and evaporated to yield 120 mg (81%) of iso-propyl
benzoate 11 as a colorless liquid.
Partial Transesterification of Methyl Benzoate 1
A solution, prepared by stirring 57 mg (1.5 mmol) of sodium borohydride, 3 ml
of ethanol, and 0.5 ml (6.8 mmol) of acetone for 30 min at rt in a closed vial, was stir-
red with 0.1 ml (0.79 mmol) of methyl benzoate 1 for 4 h at rt, poured into 20 ml of
1 M HCl, and extracted with ether. The organic layer was dried over MgSO4, filtered,
1
and evaporated to yield 123 mg of a colorless liquid, which consisted (by H NMR)
of ethyl benzoate 2 and starting methyl benzoate 1 in the molar ratio of 1:1 (50%
conversion).
Selective Reduction of Methyl 11-Acetylthioundecanoate 14
A mixture of methyl 11-acetylthioundecanoate 14 (23 mg, 0.08 mmol), sodium
borohydride (24 mg, 0.64 mmol), and tert-butanol (1 ml) was stirred for 31 h at room
temperature, acidified with 1 M HCl, and extracted with ethyl acetate. The organic
layer was dried over MgSO4, filtered, and evaporated to give 16 mg of viscous oil,
which consisted (by 1H NMR) of methyl 11-mercaptoundecanoate 15 and the disul-
fide 16 in the molar ratio of 1.5:1. This material was stirred with one drop of tribu-
tylphosphine, 3 ml of chloroform, and one drop of water for 10 min and evaporated
1
in vacuum. H NMR analysis (d 2.86 for CH2, connected to the acetylthio-group, d
2.53 for CH2, connected to the mecrapto-group, and d 2.68 for CH2, connected to
the disulfide group) of the residue showed complete reduction of the disulfide to
the mercapto-group.
Reduction of 11-Acetylthioundecanoic Acid 17 in Ethanol
A mixture of 11-acetylthioundecanoic acid 17 (25 mg, 0.096 mmol), sodium
borohydride (30 mg, 0.79 mmol), and ethanol (2 ml) was stirred for 4 h at rt, acidified
with 1 M HCl, and extracted with ethyl acetate. The organic layer was dried over
MgSO4, filtered, and evaporated to give 19 mg (90%) of 11-mercaptoundecanoic
acid 18.

1320
G. SEREDA, S. POTHULA, AND J. DREESSEN
Attempted Reduction of 11-Acetylthioundecanoic Acid 17 in
iso-Propanol
A mixture of 11-acetylthioundecanoic acid 17 (25 mg, 0.096 mmol), sodium
borohydride (30 mg, 0.79 mmol), and ethanol (2 ml) was stirred for 4 h at rt, acidified
with 1 M HCl, and extracted with ethyl acetate. The organic layer was dried over
MgSO4, filtered, and evaporated to give 25 mg (100%) of the starting acid 17.
Methyl 11-Benzoylthioundecanoate 19
A mixture of 11-benzoylthioundecanoic acid 20 (58 mg, 0.18 mmol), DCC
(41 mg, 0.20 mmol), and 4-dimethylaminopyridine (DMAP; 5 mg) was stirred in
3 ml of methanol at room temperature for 4 h, evaporated in vacuum, dissolved
in 2 ml of ether, filtered, and evaporated to give 63 mg of impure methyl
11-benzoylthioundecanoate 19. The crude material was chromatographed on a
silica-gel column eluted by 5% ethyl acetate in hexane to yield a pure sample of 19
1
as colorless oil. H NMR (CHCl3) d 1.2–1.8 (m., 16H), 2.30 (t., 2H), 3.05 (t., 2H),
3.65 (s., 3H), 7.4–7.6 (m., 3H), 7.95 (d., 2H). Anal. C19H28SO3 calc. (%): C, 67.82;
H, 8.39. Found: C, 67.88; H, 8.58.
Covalent Attachment of 11-Acetylthioundecanoic Acid 17[22] to
Wang Resin
A mixture of Wang resin (935 mg, 1.6 mmol=g, 1.5 mmol), DCC (225 mg,
1.1 mmol), DMAP (25 mg), 11-acetylthioundecanoic acid 17 (260 mg, 1 mmol), and
9 ml of DMF was shaken for 16 h, filtered, washed with DMF (3 ꢀ 7 ml), DCM
(3 ꢀ 7 ml), and methanol (2 ꢀ 7 ml), and dried in air at rt for 16 h.
ACKNOWLEDGMENTS
We thank the state of South Dakota (2010 Research Initiative), NSF-NPURC
(National Science Foundation–Northern Plains Undergraduate Research Center,
Award 0532242), and the University of South Dakota (Research Catalyst Award)
for financial support of this work.
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