Use of tosylated glycerol carbonate to access N-glycerylated aza-aromatic species

Article abstract of DOI:10.1016/j.tet.2013.03.002

Tosylated glycerol carbonate was used for N-glyceryl functionalization of diverse aza-aromatic systems. Depending on the pK_a of the aza-heterocycle and the reaction conditions applied, original N-alkylated or N-acylated aza-heterocyclic derivat

Full text of DOI:10.1016/j.tet.2013.03.002

Tetrahedron 69 (2013) 3721e3727
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Use of tosylated glycerol carbonate to access N-glycerylated
aza-aromatic species
a
b
a
c
_
_
ꢀ
ꢀ
_
Gyte Vilkauskaite , Sonata Krikstolaityte , Osvaldas Paliulis , Patrick Rollin ,
c
,
a,
*
ꢀ
*
€
Arnaud Tatibouet , Algirdas Sackus
a
_
Institute of Synthetic Chemistry, Kaunas University of Technology, Radvilenu˛ pl. 19, LT-50254 Kaunas, Lithuania
Department of Organic Chemistry, Kaunas University of Technology, Radvilenu˛ pl. 19, LT-50254 Kaunas, Lithuania
ICOA-UMR 7311, Universite d’Orleans, Rue de Chartres BP 6759, F-45067 Orleans, France
b
c
_
ꢁ
ꢁ
ꢁ
a r t i c l e i n f o
a b s t r a c t
Article history:
Tosylated glycerol carbonate was used for N-glyceryl functionalization of diverse aza-aromatic systems.
Depending on the pKa of the aza-heterocycle and the reaction conditions applied, original N-alkylated or
N-acylated aza-heterocyclic derivatives were obtained. Those compounds carry an electrophilic appen-
dagedeither carbonate or epoxidedwhich allows further useful transformations.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 19 September 2012
Received in revised form 13 February 2013
Accepted 4 March 2013
Available online 13 March 2013
Keywords:
Glycerol
Heterocycles
Tosylates
Carbonates
Carbamates
Oxiranes
1. Introduction
also take part in ring-opening polymerisation reactions.3 The pri-
mary hydroxyl functionality also broadens the reactivity scope of
The possibility of using glycerol in the creation of value-added
chemicals has become increasingly attractive in recent years,
partly from the manufacture of biodiesel, where glycerol is formed
in large amounts as the main by-product and partly from the re-
newable aspect of the chemistry developed.1 Among the readily
accessible molecules obtained from glycerol, the cyclic 1,2-
carbonate (4-hydroxymethyl-1,3-dioxolan-2-one) 1da stable, low
vapour pressure, colourless liquid is one major renewable target in
glycerol chemistry. Glycerol 1,2-carbonate (GC) is a relatively new
and interesting bio-degradable material that can be used as a non-
toxic solvent in cosmetics, medicine and industry.2 In addition to
these applications GC, as a bifunctional organic compound, has
considerable potential for use as a reagent or a building block in fine
chemistry. Five-membered cyclic alkylene carbonates are highly
reactive species, which can easily undergo a number of reactions
with various nucleophiles, such as amines, alcohols, thiols, and can
GC as a nucleophile. Treatment of GC with anhydrides,4 arylsulfonyl
chlorides,4c isocyanates5 readily affords esters, sulfonates and
urethanes, respectively. GC nucleophilicity has been used in gly-
coside synthesis by reaction with saccharides under acid catalysis.6
As an inexpensive industrial starting material, GC has been ap-
plied in the elaboration of surfactants4a and polymeric materials.5,7
It can easily be converted into glycidol and epichlorohydrindhigh
value monomers for macromolecular applications.4b,8 More re-
cently, an advanced building block of GC has been introduced
through its conversion into the tosylated form as a new valuable
starting material for fine chemistry or polymer applications. Tosy-
lated glycerol 1,2-carbonate (TGC) has also found use as an initiator
for cationic ring-opening polymerisations.9
The reactivity of O-sulfonylated GCsdeither mesylate or tosy-
latedhas been explored with various thiols, alcohols and amines as
nucleophiles aiming at selectively mono- or bis-functionalised 3-
carbon synthons.10 In this regard, TGC underwent chemoselective
reactions (Scheme 1). With aliphatic primary and secondary amines
and aliphatic alkoxides, ring-opening of the cyclic carbonate
occurred. Aminolysis afforded (2-hydroxy-3-tosylpropyl)carba-
mates, further transformed into the corresponding glycidyl
* Corresponding authors. Tel.: þ33 238494854; fax: þ33 238417281 (A.T.);
tel.: þ370 37451401; fax: þ370 37451432 (A.S.); e-mail addresses: arnaud.
ꢀ
€
ꢀ
tatibouet@univ-orleans.fr (A. Tatibouet), algirdas.sackus@ktu.lt (A. Sackus).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.002

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G. Vilkauskaite et al. / Tetrahedron 69 (2013) 3721e3727
3722
alkylcarbamates, which can be seen as protected intermediates of
glycidol derivatives.10b Alkoxides reacted to afford glycidyl car-
bonates, whereas the reactivity observed with softer nucleophiles
was centred on the glycerol sulfonylated site.
mixture by LC/MS and 1H NMR spectroscopy revealed also the
formation of high molecular weight side products. Variations of the
reaction parameters such as reaction temperature and time, and
the use of DEAD as a Mitsunobu reagent, did not result in a signif-
icant improvement of the yield of the target product.
O
O
O
glycerol
HO
1
RXH = ArNH2, ArSH, alkylSH,
base (K2CO3, Et3N), DMF
O
O
TsCl, DMAP,
pyridine
O
RX
O
O
3
O
TsO
RR'NH (R = alkyl, R' = H or alkyl).
no base, THF
2
Scheme 2. Reactions of benzimidazole with TGC 2 and GC 1.
OH
ROH, NaH,
THF
TsO
O
NRR'
Comparatively, the more acidic 1H-benzotriazole was then in-
vestigated. It is known that the ambident anion of benzotriazole
reacts with electrophiles to afford mixtures of 1- and 2-substituted
regioisomers.18 Reacting TGC 2 at room temperature with the
benzotriazolyl anion generated with NaH in DMF afforded an
equimolar mixture of N-alkylated regioisomers 8 and 9 in 85%
global yield. As expected, applying the Mitsunobu reaction to 1H-
benzotriazole with 1,2-glycerol carbonate 1 regioselectively affor-
ded the 2-substituted product 9 in 57% yield (Scheme 3).
CH3ONa,
CH3OH
O
O
4
O
OR
O
O
NRR'
O
5
6
O
Scheme 1. Reactivity of TGC 2.
Our current interest in developing TGC seeked for extension of
its abilities as a bis-electrophile with involvement of a new family
of aza-nucleophiles based on heteroaromatic structures containing
an acidic NeH bond. In this regard, our aim was to explore the site
selectivity and the potentiality to develop new building blocks for
fine organic chemistry. Reacting aza-heteroaromatics with TGC
would lead to molecular hybrids in which the aryl system is N-
connected to a glyceryl-derived appendage, thus delivering build-
ing blocks of general interest in the preparation of pharmaceuticals
and advanced materials particularly.11
2. Results and discussion
Scheme 3. Reactions of benzotriazole with TGC 2 and GC 1.
X-ray crystallographic study of 8 (Fig. 1)19 was performed to
Stable crystalline TGC 2 was prepared in quantitative yield from
GC 1 following our previously described procedure (TsCl in the
presence of pyridine and DMAP in dichloromethane).10a Reagent 2
was confronted to different NH-containing aza-heteroaromatics,
namely 9H-carbazole, 1H-indole, 1H-benzimidazole and 1H-ben-
zotriazole. All of the above mentioned heterocycles are NeH acids,
with pKa values (measured in DMSO) ranging between 20.95 (for
1H-indole) and 11.9 (for 1H-benzotriazole).12 The direct nucleo-
philicity of these aromatic NH-heterocycles is very weak and re-
quires deprotonating activation to the corresponding anion.13 The
N-alkylation of heterocyclic compounds bearing a NeH acidic hy-
drogen atom is accomplished either by treatment of the substrate
with a base such as sodium hydride, potassium hydroxide or n-BuLi,
followed by reaction of the resulting anion with an alkylating
agent,14 or by direct N-alkylation under phase-transfer catalysis
conditions.14a,c,15 Another alternative alkylation method involves
Mitsunobu reaction of NeH heteroaromatics with alcohols.16
The study was initiated with 1H-benzimidazole. Alkylation of
ambident benzimidazole anion with alkyl halides or alkyl sulfo-
nates can be readily accomplished in both protic and aprotic sol-
vents.17 The reaction of TGC 2 with the benzimidazole anion
generated with NaH in DMF afforded the crystalline carbonate 7 in
76% yield using a 1:1 stoichiometric ratio of reactants. The forma-
tion of the N-acylated derivative was not observed. A comparative
direct N-alkylation of 1H-benzimidazole with GC 1 using Mitsu-
nobu reaction conditions (DIAD, Ph3P, THF) afforded compound 7 in
only 29% yield (Scheme 2). Analysis of the unpurified reaction
ascertain the regioisomeric issue in both reactions.20
Fig. 1. ORTEP drawing of compound 8.
Switching to less acidic aza-heterocyclic systems, we now con-
sidered the reaction of 1H-indole derivatives.21 Indole 10 has
shown in some cases to undergo exclusive N-alkylation, whereas
different conditions oriented substitution at C-3. The rate and
regioselectivity of the reaction mainly depend on the solvent, the
counter-cation and on the structure of the electrophilic partner.
The reaction of TGC 2 with deprotonated 1H-indole in DMF
exclusively gave N-alkylated compound 10a in 34% yield (Table 1,
entry 1). When performed in THF instead of DMF, the reaction
afforded compound 10b in 39% yield (Table 1, entry 2). Low yield of
the both reactions can be explained by the tendency of 3-
unsubstituted indoles to polymerize (Scheme 4).22

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G. Vilkauskaite et al. / Tetrahedron 69 (2013) 3721e3727
3723
Table 1
Products and yields of the reaction of indole derivatives 10e13 with TGC 2
N
N
N
N
O
H
N
Entry
Substrate
Solvent
Cyclic carbonate a
Glycidyl carbamate b
+
O
O
N
H
1
2
3
4
5
6
10
10
11
12
12
13
DMF
THF
DMF
DMF
THF
10a (34%)
10a (e)
11a (48%)
12a (53%)
12a (e)
10b (e)
10b (39%)
11b (e)
12b (10%)
12b (64%)
13b (51%)
4:1
O
OH
HO
allyl amine,
THF, rt, 7 h
16
17
NaBH4, EtOH,
reflux, 3 h
N
N
DMF
13a (e)
EtOH, Et3N,
reflux, 5 h
N
N
OH
7
35% aq. HCl,
50 °C, 7 h
CO2Me
O
OH
14 (88 and 83%)
:
NH
O
O
N
N
H
N
H
N
H
OH
H
11
10
13
12
methyl 2-mercaptoacetate,
DMF, K2CO3, 80 °C, 4 h
15 (68%)
N
N
O
O
NaH, then 2
DMF or THF
O
O
NH
+
N
O
N
O
S
a
b
O
18 (60%)
OH
O
Scheme 4. Reaction of indole derivatives 10e13 with TGC 2.
Scheme 5. Reactivity of carbonate 7.
It is known that the cleavage of five-membered carbonate rings
using aliphatic amines leads to the formation of carbamate deriv-
atives.10b When compound 7 was treated with allylamine in THF at
room temperature, TLC monitoring of the reaction showed an ap-
parently clean conversion. However, NMR spectra revealed that the
purified product was in fact a non-separable 4:1 mixture of iso-
meric carbamates 16 and 17 (Scheme 5).
Finally, the softer nucleophile methyl 2-mercaptoacetate was
reacted on the cyclic carbonate 7 in DMF under basic conditions.
Ring-opening by the thiol occurred regioselectively at the primary
position to give the sulfide 18 in 60% yield.
In other respects, the glycidyl carbamates 10be13b can also be
considered for further structural modifications through epoxide
ring opening. For example, when reacted with aniline at 110 ꢀC, the
glycidyl carbamate 12b underwent regioselective ring-opening to
form the corresponding aminoalcohol 19 in 20% yield, together
with the bis-alkylated aniline 20 in 51% yield (Scheme 6).
Reacting methyl 1H-indole-3-carboxylate 11 in DMF under the
same conditions selectively afforded the N-alkylated compound
11a in a much better yield than with indole (Table 1, entry 3). This
result is consistent with the enhanced mobility of the NeH bond
under the influence of the EWG in position 3.
The reaction of TGC 2 with deprotonated carbazole 12 in DMF
(Table 1, entry 4) afforded a mixture of N-alkylated product 12a and
glycidyl carbamate 12b, with 5:1 selectivity and a 63% overall
yield.23 When performed in THF instead of DMF the reaction
afforded compound 12b in 64% yield (Table 1, entry 5). Finally, the
reaction of TGC 2 with deprotonated 1,2,3,4-tetrahydrocyclopenta
[b]indole 13 in DMF afforded selectively the glycidyl carbamate
13b in 51% yield (Table 1, entry 6).
Thus it appears that the pKa of the NeH bond in the aza-
aromatic moieties stands as a critical parameter in the reaction
with TGC 2 in DMF, N-alkylation being privileged over N-acylation
for most acidic systems. In other respects, we have shown that
selectivity inversion can be induced by use of a less polar solvent, so
that involvement of a marked solvation process also has to be
considered.
With a view to evaluating the synthetic potential of the elabo-
rated N-glycerylated aza-aromatic hybrids as building blocks for
the preparation of more complex structures, the reactivity of
benzimidazole-derived carbonate 7 was explored under various
conditions. Applying either reductive (sodium borohydride in
ethanol) or hydrolytic (35% hydrochloric acid) conditions to com-
pound 7 provoked decarboxylative ring cleavage of the cyclic car-
bonate to deliver the related diol 14 in 88 and 83% yield,
respectively (Scheme 5). Compound 14 is an acyclic nucleoside
analogue known to possess antiviral activity.24 It was also used in
the synthesis of ATP analogues designed as potential glutamine
synthetase inhibitors.25 The previously reported methods for the
preparation of 14 included alkylation reactions of benzimidazole
with 3-bromo-1,2-propandiol (yield 57%),24c with the correspond-
ing bromoketal and further acidic hydrolysis of the intermediate 1-
(1,3-dioxolan-4-ylmethyl)-1H-benzimidazole derivative (overall
yield of 37% for the two steps)25 and with allylbromide followed by
cis-hydroxylation using a mixture of silver acetate and iodine in
acetic acid (overall yield of 24%).24a
OH
H
N
N
O
O
N
O
NH2
chlorobenzene,
110 °C, 6 h
19 (20%)
+
+
12b
OH
N
OH
O
N
O
O
20 (51%)
Scheme 6. Reaction of glycidyl carbamate 12b with aniline.
3. Conclusion
In summary, tosylated glycerol carbonate 2 has proven to be
a useful bis-electrophilic reagent to access N-glycerylated aza-
aromatic species. Depending on the pKa of the aza-heterocycle
and modulating the reaction conditions, a synthetic way is open
to original N-alkylated or N-acylated benzimidazole, benzotriazole
and indoles. In turn, those new aza-aromatic species carry an
electrophilic appendagedeither carbonate or epoxidedwhich al-
lows further conversions aimed at building up more complex
molecules bearing aza-aromatic tags.
Ethanolysis of compound 7 in the presence of triethylamine also
resulted in ring cleavage of the cyclic carbonate, affording the
mixed carbonate 15 in reasonable yield (Scheme 5).

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G. Vilkauskaite et al. / Tetrahedron 69 (2013) 3721e3727
3724
4. Experimental section
4.2.2. 4-(1H-Benzotriazol-1-ylmethyl)-1,3-dioxolan-2-one (8) and 4-
(2H-benzotriazol-2-ylmethyl)-1,3-dioxolan-2-one (9)
4.1. General
4.2.2.1. Method A. To a solution of 1H-benzotriazole (179 mg,
1.5 mmol) in anhydrous DMF (5 mL) NaH (60 mg, 1.5 mmol, 60% in
mineral oil) was added and the resulting slurry was stirred at rt for
15 min under inert atmosphere. Tosylate 2 (272 mg, 1.0 mmol) was
then added and the reaction mixture was stirred at rt for 5 h. The
solvent was removed under reduced pressure and the residue was
partitioned between ethyl acetate (20 mL) and water (20 mL). The
aqueous phase was extracted with ethyl acetate (3ꢁ20 mL). The
combined organic phase was washed with brine and dried over
anhydrous sodium sulfate. After solvent removal under reduced
pressure, the residue was subjected to flash chromatography on
silica gel (n-hexane/ethyl acetate 1:1, v/v) to successively deliver
compounds 8 and 9.
Reagents and solvents were purchased from SigmaeAldrich or
Fluka and used without further purification. Reactions were mon-
itored by TLC analysis on precoated silica gel plates (Kieselgel
60F254, Merck). Compounds were visualized with UV light and
charring after 1% KMnO4 solution spray. Column chromatography
was performed on silica gel SI 60 (43e60
m
m, E. Merck). Melting
€
points were determined in open capillary tubes with a Buchi B-540
melting point apparatus and are uncorrected. Infrared spectra were
recorded on a Perkin Elmer Spectrum One spectrometer using
potassium bromide pellets; for liquid samples, a thin film between
two KRS-5 plates was prepared. 1H NMR spectra were recorded at
300 MHz on a Varian Unity Inova spectrometer and at 400 MHz on
a Bruker Avance DPX-400 spectrometer. 13C NMR spectra were
registered using the same instruments at 75 and 100 MHz, re-
spectively. Chemical shifts are expressed in parts per million (ppm)
downfield from TMS and coupling constants J referring to apparent
peak multiplicity are reported in hertz (Hz). Mass spectra were
recorded on an Agilent 110 (series MS with VL) apparatus. HRMS
spectra were recorded on a Bruker maXis 4G spectrometer.
Elemental analyses were conducted using an Elemental
Analyzer CE-440 (Exeter Analytical, Inc.) by the Microanalytical
Laboratory, Department of Organic Chemistry, Kaunas University of
Technology.
Compound 8: white crystals, yield 90 mg (41%), mp 172e174 ꢀC.
Rf¼0.15 (n-hexane/ethyl acetate 1:1, v/v). 1H NMR (300 MHz,
DMSO-d6):
d
4.39 (dd, 1H, J¼8.7, 6.0 Hz, H-5b), 4.70 (t, 1H,
2J¼3J¼8.7 Hz, H-5a), 5.11e5.24 (m, 2H, NCH2), 5.29e5.37 (m, 1H, H-
4), 7.40e7.46 (m, 1H, ArH), 7.57e7.63 (m, 1H, ArH), 7.90e7.94 (m,
1H, ArH), 8.06e8.09 (m, 1H, ArH). 13C NMR (75 MHz, DMSO-d6):
d
49.2 (CH2N), 66.7 (C-5), 75.2 (C-4), 110.8, 119.1, 124.2, 127.7, 133.5,
145.0, 154.2 (C]O). IR (cmꢂ1): 1792 (C]O), 1456, 1386, 1317, 1299,
1157, 1147, 1069, 1017, 770, 755. MS (APCIþ): m/z 220.5 [MþH]þ.
Anal. Calcd for C10H9N3O3 (219.20): C, 54.79; H, 4.14; N, 19.17.
Found: C, 54.54; H, 4.42; N, 18.90.
Compound 9: white crystals, yield 96 mg (44%), mp 124e125 ꢀC.
Rf¼0.33 (n-hexane/ethyl acetate 1:1, v/v). 1H NMR (300 MHz,
DMSO-d6):
d
4.45 (dd, 1H, J¼8.4, 6.0 Hz, H-5b), 4.71 (t, 1H,
4.2. Synthetic procedures
2J¼3J¼8.4 Hz, H-5a), 5.21 (d, 2H, J¼5.1 Hz, NCH2), 5.42e5.52 (m, 1H,
H-4), 7.43e7.50 (m, 2H, ArH), 7.91e7.98 (m, 2H, ArH). 13C NMR
4.2.1. 4-(1H-Benzimidazol-1-ylmethyl)-1,3-dioxolan-2-one (7)
(75 MHz, DMSO-d6):
d 57.2 (CH2N), 66.7 (C-5), 74.6 (C-4), 117.9,
126.8, 143.8, 154.3 (C]O). IR (cmꢂ1): 1802 and 1792 (C]O), 1451,
1389, 1163, 1112, 1075, 1014, 751. MS (APCIþ): m/z 220.4 [MþH]þ.
Anal. Calcd for C10H9N3O3 (219.20): C, 54.79; H, 4.14; N, 19.17.
Found: C, 55.07; H, 4.26; N, 18.91.
4.2.1.1. Method A. To a solution of 1H-benzimidazole (1.18 g,
10 mmol) in anhydrous DMF (20 mL) NaH (0.40 g, 10 mmol, 60% in
mineral oil) was added and the resulting slurry was stirred at rt for
30 min under inert atmosphere. The tosylate 2 (2.72 g, 10 mmol)
was then added and the reaction mixture was stirred at 80 ꢀC for
5 h. The solvent was removed under reduced pressure and the
residue was partitioned between dichloromethane (100 mL) and
water (100 mL). The aqueous phase was extracted with dichloro-
methane (3ꢁ50 mL). The combined organic phase was washed
with brine and dried over anhydrous sodium sulfate. After solvent
removal under reduced pressure, the residue was subjected to
flash chromatography on silica gel (ethyl acetate) to give com-
pound 7 as white crystals (1.65 g, 76%), mp 143e145 ꢀC. Rf¼0.10
4.2.2.2. Method B. 1H-Benzotriazole (155 mg, 1.3 mmol) and
1,2-glycerol carbonate 1 (118 mg, 1.0 mmol) were reacted as de-
scribed for 7 (method B) with diisopropyl azodicarboxylate (263 mg,
0.256 mL,1.3 mmol) and Ph3P (340 mg,1.3 mmol) in anhydrous THF
(5 mL). Standard workup afforded 9. Yield 125 mg (57%).
4.2.3. 4-(1H-Indol-1-ylmethyl)-1,3-dioxolan-2-one (10a) and oxiran-
2-ylmethyl 1H-indole-1-carboxylate (10b)
(ethyl acetate). 1H NMR (300 MHz, DMSO-d6):
d 4.32 (dd, 1H,
4.2.3.1. Reaction in DMF. Reacting 1H-indole 10 (176 mg,
1.5 mmol) with NaH (60 mg, 1.5 mmol, 60% in mineral oil), then
tosylate 2 (272 mg, 1.0 mmol) in anhydrous DMF (5 mL) as de-
scribed for 7 (method A) delivered compound 10a as yellowish
crystals (74 mg, 34%), mp 90e91 ꢀC (lit. mp 91.4e92.4 ꢀC).22 Rf¼0.24
(n-hexane/ethyl acetate 2:1, v/v). 1H NMR (300 MHz, DMSO-d6):
J¼6.3, 8.8 Hz, H-5b), 4.63e4.73 (m, 3H, H-5a, NCH2), 5.16e5.22 (m,
1H, H-4), 7.22e7.31 (m, 2H, ArH), 7.68e7.72 (m, 2H, ArH), 8.23 (s,
1H, ArH). 13C NMR (75 MHz, DMSO-d6):
d 46.1 (CH2N), 66.7 (C-5),
75.4 (C-4), 110.6, 119.4, 121.7, 122.6, 133.9, 143.1, 144.2, 154.2 (C]
O). IR (cmꢂ1): 1786 (C]O), 1500, 1485, 1460, 1271, 1165, 1077, 1027,
751. MS (APCIþ): m/z 219.4 [MþH]þ. Anal. Calcd for C11H10N2O3
(218.21): C, 60.55; H, 4.62; N, 12.84. Found: C, 60.34; H, 4.72; N,
13.03.
d
4.24 (dd, 1H, J¼8.4, 6.3 Hz, H-5b), 4.57e4.64 (m, 3H, H-5a, NCH2),
5.09e5.18 (m, 1H, H-4), 6.50 (dd, 1H, J¼3.0, 0.3 Hz, H-3-indolyl),
7.02e7.08 (m,1H, ArH), 7.14e7.20 (m,1H, ArH), 7.36 (d,1H, J¼3.0 Hz,
H-2-indolyl), 7.55e7.60 (m, 2H, ArH). 13C NMR (75 MHz, DMSO-d6):
4.2.1.2. Method B. Diisopropyl azodicarboxylate (263 mg,
0.26 mL, 1.3 mmol) was added dropwise in the dark at rt to a so-
lution containing 1,2-glycerol carbonate 1 (153 mg, 1.3 mmol), 1H-
benzimidazole (154 mg, 1.3 mmol) and Ph3P (340 mg, 1.3 mmol) in
anhydrous THF (5 mL) under inert atmosphere. After 5 h stirring at
rt, water (20 mL) was added and the aqueous phase was extracted
with ethyl acetate (3ꢁ20 mL). The combined organic extract was
washed with brine, dried over anhydrous sodium sulfate. After
solvent removal under reduced pressure, the residue was subjected
to flash chromatography on silica gel (ethyl acetate) to afford
compound 7 (82 mg, 29%).
d
47.3 (CH2N), 66.7 (C-5), 76.0 (C-4), 101.5, 109.9, 119.3, 120.4, 121.3,
128.0, 129.0, 136.1, 154.4 (C]O). IR (cmꢂ1): 1785 and 1740 (C]O),
1513, 1477, 1461, 1397, 1311, 1244, 1162, 1078, 1049, 765, 741. MS
(APCIþ): m/z 218.4 [MþH]þ.
4.2.3.2. Reaction in THF. To a solution of 1H-indole 10 (117 mg,
1.0 mmol) in anhydrous THF (8 mL), NaH (40 mg, 1.0 mmol, 60% in
mineral oil) was added and the resulting slurry was stirred at rt for
15 min under inert atmosphere. The tosylate 2 (408 mg, 1.5 mmol)
was then added and the reaction mixture was stirred at rt for 12 h.

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G. Vilkauskaite et al. / Tetrahedron 69 (2013) 3721e3727
3725
The solvent was removed under reduced pressure and the residue
was partitioned between dichloromethane (20 mL) and water
(20 mL). The aqueous phase was extracted with dichloromethane
(3ꢁ10 mL). The combined organic phase was washed with brine
and dried over anhydrous sodium sulfate. After solvent removal
under reduced pressure, the residue was subjected to flash chro-
matography on silica gel (n-hexane/ethyl acetate 5:1, v/v) to afford
compound 10b as a yellow liquid (85 mg, 39%). Rf¼0.50 (n-hexane/
4.32 (dd, 1H, J¼12.0, 6.9 Hz, COOCHb), 4.88 (dd, 1H, J¼12.0, 2.7 Hz,
COOCHa), 7.38e7.44 (m, 2H, ArH), 7.50e7.56 (m, 2H, ArH),
8.15e8.18 (m, 2H, ArH), 8.24e8.26 (m, 2H, ArH). 13C NMR (75 MHz,
DMSO-d6): d 44.0, 48.8, 67.6, 115.8 (2C), 120.1 (2C), 123.5 (2C), 125.2
(2C), 127.4 (2C), 137.4 (2C), 151.3 (C]O). IR (cmꢂ1) 1727 (C]O),
1490, 1447, 1377, 1324, 1257, 1220, 1205, 1049, 761, 749. Anal. Calcd
for C16H13NO3 (267.28) C, 71.90; H, 4.90; N, 5.24. Found: C, 71.80; H,
4.96; N, 5.13. ESI-HRMS: [MþNa]þ, found 290.0788. C16H13NNaO3
requires 290.0787.
ethyl acetate 5:1, v/v). 1H NMR (300 MHz, DMSO-d6):
d 2.79 (dd, 1H,
J¼5.0, 2.6 Hz, H-3b-oxiranyl), 2.88 (t, 1H, J¼4.8 Hz, H-3a-oxiranyl),
3.42e3.46 (m, 1H, H-2-oxiranyl), 4.21 (dd, 1H, J¼12.0, 6.3 Hz,
COOCHb), 4.79 (dd, 1H, J¼12.3, 2.7 Hz, COOCHa), 6.76 (d, 1H,
J¼3.6 Hz, H-3-indolyl), 7.24e7.29 (m, 1H, ArH), 7.32e7.38 (m, 1H,
ArH), 7.63e7.66 (m, 1H, ArH), 7.72 (d, 1H, J¼3.7 Hz, H-2-indolyl),
4.2.5.2. Reaction in THF. Reacting 9H-carbazole (167 mg,
1.0 mmol) with tosylate 2 (408 mg, 1.5 mmol) in anhydrous THF
(8 mL) as described for 10b afforded compound 12b (158 mg, 64%
yield).
8.09e8.10 (m, 1H, ArH). 13C NMR (75 MHz, DMSO-d6):
d 43.8, 48.8,
67.5,108.3, 114.6,121.2,123.0,124.5,125.8, 130.1,134.5, 150.1 (C]O).
IR (cmꢂ1): 1740 (C]O), 1456, 1387, 1360, 1327, 1244, 1211, 1120,
1082, 1120, 762. ESI-HRMS: [MþH]þ, found 218.0810. C12H12NO3
requires 218.0812.
4.2.6. Oxiran-2-ylmethyl 2,3-dihydrocyclopenta[b]indole-4(1H)-car-
boxylate (13b). To a solution of 1,2,3,4-tetrahydrocyclopenta[b]in-
dole 13 (118 mg, 0.75 mmol) in anhydrous DMF (4 mL), NaH (30 mg,
0.75 mmol, 60% in mineral oil) was added and the resulting slurry
was stirred at rt for 15 min under inert atmosphere. Tosylate 2
(204 mg, 0.75 mmol) was then added and the reaction mixture was
stirred at rt for 6 h. The solvent was removed under reduced
pressure and the residue was partitioned between dichloro-
methane (15 mL) and water (15 mL). The aqueous phase was
extracted with dichloromethane (2ꢁ10 mL). The combined organic
phase was washed with brine and dried over anhydrous sodium
sulfate. After solvent removal under reduced pressure, the residue
was subjected to flash chromatography on silica gel (n-hexane/
ethyl acetate 7:1, v/v) to give compound 13b as white crystals
(98 mg, 51%), mp 113e114 ꢀC. Rf¼0.50 (n-hexane/ethyl acetate 7:1,
4.2.4. Methyl 1-[(2-oxo-1,3-dioxolan-4-yl)methyl]-1H-indole-3-
carboxylate (11a). Obtained similarly to compound 7 (method A)
from methyl 1H-indole-3-carboxylate 11 (175 mg, 1.0 mmol) and
tosylate 2 (272 mg, 1.0 mmol) as white crystals, yield 132 mg (48%),
mp 133e134 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d 3.82 (s, 3H, OCH3),
4.30 (dd, 1H, J¼8.7, 6.3 Hz, 1H, H-5b), 4.61e4.69 (m, 3H, H-5a,
NCH2), 5.13e5.22 (m, 1H, H-4), 7.22e7.33 (m, 2H, ArH), 7.70e7.73
(m, 1H, ArH), 8.02e8.05 (m, 1H, ArH), 8.16 (s, 1H, H-2-indolyl). 13C
NMR (75 MHz, DMSO-d6):
d 47.9 (CH2N), 50.7 (OCH3), 66.7 (C-5),
75.4 (C-4), 106.2, 111.0, 120.6, 121.8, 122.7, 125.9, 135.6, 136.5, 154.2
(C]O carbamate), 164.3 (C]O carboxylate). IR (cmꢂ1): 1786 (C]
O), 1694 (C]O), 1538, 1444, 1413, 1274, 1258, 1223, 1192, 1163, 1113,
1079, 1018, 756. MS (APCIþ): m/z 276.3 [MþH]þ. Anal. Calcd for
C14H13NO5 (275.26): C, 61.09; H, 4.76; N, 5.09. Found: C, 61.43; H,
4.97; N, 5.00.
v/v). 1H NMR (300 MHz, CDCl3):
d 2.46e2.58 (m, 2H, CH2CH2CH2),
2.75e2.82 (m, 3H, H-3b-oxiranyl, CH2CH2CH2), 2.94 (t,1H, J¼4.8 Hz,
H-3a-oxiranyl), 3.09e3.15 (m, 2H, CH2CH2CH2), 3.35e3.41 (m, 1H,
H-2-oxiranyl), 4.23 (dd, 1H, J¼12.3, 6.3 Hz, COOCHb), 4.73 (dd, 1H,
J¼12.3, 3.0 Hz, COOCHa), 7.21e7.32 (m, 2H, ArH), 7.36e7.43 (m, 1H,
ArH), 8.17e8.20 (m, 1H, ArH). 13C NMR (75 MHz, CDCl3):
d 24.0
(CH2-cyclopenta), 27.3 (CH2-cyclopenta), 28.8 (CH2-cyclopenta),
44.6, 49.2, 66.9, 115.7, 118.6, 123.0, 123.2, 125.5, 127.0, 140.1, 143.5. IR
(cmꢂ1): 1729 (C]O), 1615, 1453, 1381, 1323, 1295, 1217, 1114, 1033,
752. MS (APCIþ): m/z 258.5 [MþH]þ. Anal. Calcd for C15H15NO3
(257.28): C, 70.02; H, 5.88 N, 5.44. Found: C, 70.04; H, 5.92; N, 5.41.
4.2.5. 4-(9H-Carbazol-9-ylmethyl)-1,3-dioxolan-2-one (12a) and
oxiran-2-ylmethyl 9H-carbazole-9-carboxylate (12b)
4.2.5.1. Reaction in DMF. To a solution of 9H-carbazole 12 (2.0 g,
12 mmol) in anhydrous DMF (20 mL) NaH (0.48 g, 12 mmol, 60% in
mineral oil) was added and the resulting slurry was stirred at rt for
10 min under inert atmosphere. The tosylate 2 (2.0 g, 7.35 mmol)
was then added and the reaction mixture was stirred at rt for 2 h.
The solvent was removed under reduced pressure and the residue
was partitioned between ethyl acetate (100 mL) and water
(100 mL). The aqueous phase was extracted with ethyl acetate
(3ꢁ80 mL). The combined organic phase was washed with brine
and dried over anhydrous sodium sulfate. After solvent removal
under reduced pressure, the residue was subjected to flash chro-
matography on silica gel (n-hexane/ethyl acetate, 5:1/3:1, v/v) to
deliver compounds 12a and 12b.
4.2.7. 3-(1H-Benzimidazol-1-yl)propane-1,2-diol (14)
4.2.7.1. Via reduction. NaBH4 (57 mg, 1.5 mmol) was added
portionwise to a refluxing solution of compound 7 (218 mg,
1.0 mmol) in anhydrous ethanol (6 mL) and reflux was maintained
for 3 h under inert atmosphere. After cooling and removal of the
solvent under reduced pressure, the residue was subjected to flash
chromatography on silica gel (dichloromethane/methanol 10:1, v/
v) to afford compound 14 (Rf¼0.38) as white crystals (170 mg, 88%),
mp 58e59 ꢀC (lit. mp 60e61 ꢀC).24a 1H NMR (300 MHz, DMSO-d6):
d
3.27e3.57 (m, 2H, CH2OH), 3.76e3.86 (1H, m, CHOH), 4.13 (dd, 1H,
Compound 12a: white crystals, yield 1.04
g (53%), mp
189e190 ꢀC (lit. mp 189.6e191.1 ꢀC).22 Rf¼0.20 (n-hexane/ethyl
J¼14.4, 7.5 Hz, NCHb), 4.36 (dd, 1H, J¼14.4, 3.3 Hz, NCHa), 4.90 (br s,
1H, OH), 5.12 (br s, 1H, OH), 7.16e7.27 (m, 2H, ArH), 7.57e7.66 (m,
2H, ArH), 8.13 (s, 1H, ArH). 13C NMR (75 MHz, DMSO-d6): 47.4
(CH2N), 63.2 (CH2OH), 70.0 (CHOH), 110.6, 119.2, 121.2, 122.0, 134.3,
143.2, 144.7. IR (cmꢂ1): 3345e3100 (OeH), 1499, 1460, 1383, 1262,
1200, 1116, 1043, 744.
acetate 3:1, v/v). 1H NMR (300 MHz, DMSO-d6):
d 4.33 (dd, 1H,
J¼8.7, 6.9 Hz, H-5b), 4.67e4.91 (m, 3H, H-5a, NCH2), 5.19e5.28 (m,
1H, H-4), 7.21e7.26 (m, 2H, ArH), 7.44e7.50 (ArH), 7.71e7.74 (m, 2H,
ArH), 8.15e8.18 (m, 2H, ArH). 13C NMR (75 MHz, DMSO-d6):
d 44.7
(CH2N), 66.9 (C-5), 76.0 (C-4), 109.6 (2C), 119.2 (2C), 120.2 (2C),
122.2 (2C), 125.8 (2C), 140.3 (2C), 154.5 (C]O). IR (cmꢂ1) 1806 and
1780 (C]O), 1483, 1455, 1183, 1164, 1096, 1042, 748. ESI-HRMS:
[MþNa]þ, found 290.0787. C16H13NNaO3 requires 290.0787.
Compound 12b: white crystals, yield 196 mg (10%), mp 86e87 ꢀC.
Rf¼0.50 (n-hexane/ethyl acetate 5:1, v/v). 1H NMR (300 MHz,
4.2.7.2. Via hydrolysis. Compound 7 (109 mg, 0.5 mmol) was
dissolved in 35% aq HCl (2 mL) and the mixture was stirred at 50 ꢀC
for 7 h. After cooling, the reaction mixture was poured into a satu-
rated Na2CO3 solution (5 mL) and the aqueous phase was extracted
with ethyl acetate (3ꢁ10 mL). The combined organic extract was
dried over anhydrous sodium sulfate. After solvent removal under
DMSO-d6):
d
2.82 (dd, 1H, J¼4.8, 2.7 Hz, H-3b-oxiranyl), 2.92 (dd,
1H, J¼5.1, 4.2 Hz, H-3a-oxiranyl), 3.50e3.56 (m, 1H, H-2-oxiranyl),

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G. Vilkauskaite et al. / Tetrahedron 69 (2013) 3721e3727
3726
reduced pressure, the residue was subjected to flash chromatog-
raphy on silica gel (dichloromethane/methanol, 10:1) to afford 14
(80 mg, 83% yield).
aqueous phase was extracted with dichloromethane (3ꢁ10 mL) and
the combined organic phase was washed with brine, then dried
over anhydrous sodium sulfate. After solvent removal under re-
duced pressure, the residue was subjected to flash chromatography
on silica gel (dichloromethane/methanol 10:1, v/v) to afford com-
pound 18 (Rf¼0.53) as a yellow liquid (151 mg, 60%). 1H NMR
4.2.8. 3-(1H-Benzimidazol-1-yl)-2-hydroxypropyl ethyl carbonate
(15). Triethylamine (505 mg, 0.70 mL, 5.0 mmol) was added
dropwise to a refluxing solution of compound 7 (218 mg, 1.0 mmol)
in anhydrous ethanol (5 mL) and reflux was maintained for 5 h.
After solvent removal under reduced pressure, the residue was
subjected to flash chromatography on silica gel (dichloromethane/
methanol 10:1, v/v) to afford compound 15 (Rf¼0.54) as a colourless
(300 MHz, DMSO-d6):
d 2.62e2.75 (m, 2H, SCH2CH), 3.45 (s, 2H,
SCH2CO), 3.61 (s, 3H, OCH3), 3.92e4.03 (m, 1H, CHOH), 4.17 (dd, 1H,
J¼14.4, 7.8 Hz, NCHb), 4.36 (dd, 1H, J¼14.3, 3.3 Hz, NCHa), 5.43 (d,
1H, J¼5.4 Hz, OH), 7.16e7.28 (m, 2H, ArH), 7.58e7.66 (m, 2H, ArH),
8.13 (s, 1H, ArH). 13C NMR (75 MHz, DMSO-d6):
d 33.4, 36.4 (CH2S),
liquid (180 mg, 68%). 1H NMR (300 MHz, CDCl3):
d
1.33 (t, 3H,
49.2 (CH2N), 52.0 (OCH3), 68.6 (CHOH), 110.5, 119.3, 121.3, 122.1,
134.2, 143.2,144.6,170.7 (C]O). IR (cmꢂ1): 3600e3100 (OeH), 1733
(C]O), 1500, 1461, 1437, 1290, 1203, 1164, 1136, 1007, 746. ESI-
HRMS: [MþH]þ, found 281.0954. C13H17N2O3S requires 281.0954.
J¼7.1 Hz, CH3), 4.07e4.31 (m, 7H, NCH2, OCH2, CH2CH3, CHOH),
7.03e7.09 (m, 1H, ArH), 7.14e7.20 (m, 1H, ArH), 7.31e7.37 (m, 2H,
ArH), 7.65 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3):
d 14.2 (CH3), 48.3
(CH2N), 64.4, 67.3, 68.5, 109.5, 119.3, 122.3, 123.0, 133.3, 142.3, 143.5,
155.0 (C]O). IR (cmꢂ1) 3650e3100 (OeH), 1814 and 1747 (C]O),
1616, 1501, 1446, 1384, 1275, 1078, 1010, 746. MS (APCIþ): m/z 265.4
[MþH]þ. Anal. Calcd for C13H16N2O4 (264.28): C, 59.08; H, 6.10; N,
10.60. Found: C, 59.12; H, 6.31; N, 10.21.
4.2.11. 2-Hydroxy-3-(phenylamino)propyl 9H-carbazole-9-
carboxylate (19) and (phenylimino)bis-2-hydroxypropane-3,1-
diyl bis(9H-carbazole-9-carboxylate), (20, mixture of diaster-
eomers). The glycidyl carbamate 12b (188 mg, 0.70 mmol), aniline
(32 mg, 0.35 mmol) and a few drops of chlorobenzene were heated
at 110 ꢀC for 6 h. After cooling, the mixture was subjected to flash
chromatography on silica gel (n-hexane/ethyl acetate 3:1, v/v) to
successively afford compounds 19 (Rf¼0.3) and 20 (Rf¼0.43).
Compound 19: white solid, yield 50 mg (20%), mp 117e118 ꢀC. 1H
4.2.9. 3-(1H-Benzimidazol-1-yl)-2-hydroxypropyl prop-2-en-1-
ylcarbamate (16) and 2-(1H-benzimidazol-1-yl)-3-hydroxypropyl
prop-2-en-1-ylcarbamate (17). Allylamine (91 mg, 0.12 mL,
1.60 mmol) was added dropwise to a solution of compound 7
(169 mg, 0.78 mmol) in anhydrous THF (4 mL) under inert atmo-
sphere and the mixture was stirred for 7 h at rt. The solvent was
removed under reduced pressure and the residue was partitioned
between ethyl acetate (10 mL) and water (15 mL). The aqueous
phase was extracted with ethyl acetate (3ꢁ10 mL) and the com-
bined organic phase was washed with brine, then dried over an-
hydrous sodium sulfate. After solvent removal under reduced
pressure, the residue was subjected to flash chromatography on
silica gel (dichloromethane/methanol 10:1, v/v) to afford an in-
separable mixture of the regioisomeric allylcarbamates 16 and 17
(Rf¼0.50) as a white crystalline material (201 mg, 94%). IR (cmꢂ1):
3600e3100 (NeH, OeH), 1709 (C]O), 1645, 1534, 1501, 1461, 1334,
1260, 1150, 746. MS (APCIþ): m/z 276.4 [MþH]þ. Anal. Calcd for
C14H17N3O3 (275.31): C, 61.08; H, 6.22; N, 15.26. Found: C, 61.46; H,
6.43; N, 15.11.
NMR (300 MHz, DMSO-d6):
d 3.16e3.34 (m, 2H, CH2N), 4.13e4.23
(m, 1H, CHOH), 4.49 (dd, 1H, J¼11.1, 6.3 Hz, OCHb), 4.61 (dd, 1H,
J¼11.1, 3.6 Hz, OCHa), 5.51 (d,1H, J¼5.1 Hz, OH), 5.73 (t,1H, J¼5.9 Hz,
NH), 6.51e6.56 (m, 1H, ArH), 6.63e6.66 (m, 2H, ArH), 7.05e7.10 (m,
2H, ArH), 7.38e7.43 (m, 2H, ArH), 7.49e7.54 (m, 2H, ArH), 8.16e8.18
(m, 2H, ArH), 8.32e8.35 (m, 2H, ArH). 13C NMR (75 MHz, DMSO-d6):
d
46.1 (CH2N), 66.8 (CH2O), 69.2 (CHOH), 112.1 (2C), 115.8, 116.0
(2C), 120.1 (2C), 123.4 (2C), 125.2 (2C), 127.4 (2C), 128.9 (2C), 137.6
(2C), 148.7, 151.8 (C]O). IR (cmꢂ1): 3520 (OeH), 3349 (NeH), 1730
(C]O), 1601, 1514, 1448, 1329, 1302, 1220, 1205, 1124, 1043, 762,
753. MS (APCIþ): m/z 361.3 [MþH]þ. Anal. Calcd for C22H20N2O3
(360.41): C, 73.31; H, 5.59; N, 7.77. Found: C, 73.59; H, 5.45; N, 7.60.
Compound 20: white solid, yield 113 mg (51%), mp 162e164 ꢀC.
1H NMR (300 MHz, DMSO-d6):
d
3.50e3.88 (m, 4H, 2ꢁCH2N),
4.24e4.33 (m, 2H, 2ꢁCHOH), 4.42e4.49 (m, 2H, 2ꢁOCHHb),
4.55e4.64 (m, 2H, 2ꢁOCHHa), 5.55 (d, 1H, J¼5.1 Hz, OH), 5.69 (d,
1H, J¼5.1 Hz, OH), 6.55e6.68 (m, 1H, ArH), 6.82e6.86 (m, 2H, ArH),
7.05e7.14 (m, 2H, ArH), 7.33e7.40 (m, 4H, ArH), 7.45e7.52 (m, 4H,
ArH), 8.09e8.15 (m, 4H, ArH), 8.31e8.35 (m, 4H, ArH). 13C NMR
Compound 16 (major isomer). 1H NMR (400 MHz, CDCl3):
d
3.63e3.66 (m, 2H, CH2NH), 3.85e4.06 (m, 3H, CHOH, NCH2CH),
4.20 (dd, 1H, J¼14.4, 7.4 Hz, OCHb), 4.53 (dd, 1H, J¼14.4, 3.6 Hz,
OCHa), 5.03e5.20 (m, 2H, C]CH2), 5.43 (d, 1H, J¼5.3 Hz, OH),
5.76e5.87 (m, 1H, C]CH), 7.17e7.28 (m, 2H, ArH), 7.47 (t, 1H,
J¼5.7 Hz, NH), 7.58e7.67 (m, 2H, ArH), 8.14 (s, 1H, H-2-
(75 MHz, DMSO-d6):
d
54.7 (2ꢁCH2N), 66.0 (2ꢁCH2O), 69.2
(2ꢁCHOH), 112.1 (2C), 112.3, 116.0 (4C), 120.1 (4C), 123.4 (4C), 125.2
(4C), 127.4 (4C), 129.0 (2C), 137.5 (4C), 147.7, 151.8 (2ꢁC]O). IR
(cmꢂ1): 3388 (NeH), 1732 and 1699 (C]O), 1600, 1506, 1446, 1403,
1330, 1304, 1249, 1219, 1202, 1116, 1043, 760, 749. MS (APCIþ): m/z
628.2 [MþH]þ. Anal. Calcd for C38H33N3O6 (627.70): C, 72.71; H,
5.30; N, 6.69. Found: C, 72.89; H, 5.14; N, 6.35.
benzimidazolyl). 13C NMR (100 MHz, CDCl3):
d 42.5 (CH2NH), 47.2
(CH2N), 65.2 (CH2O), 67.3 (CHOH), 110.4, 114.9 (C]CH2), 119.2,
121.3, 122.1, 134.1 (C]CH), 135.5, 143.2, 144.6, 155.9 (C]O).
Compound 17 (minor isomer). 1H NMR (400 MHz, CDCl3):
d
3.46e3.56 (m, 4H, CH2NH, CH2OH), 4.40 (1H, dd, J¼14.4, 6.8 Hz,
OCHb), 4.51 (1H, dd, J¼14.8, 4.0 Hz, OCHa), 4.87e4.93 (m, 1H, NCH),
4.97e5.10 (m, 2H, C]CH2), 5.66e5.76 (m, 1H, C]CH), 7.17e7.28 (m,
2H, ArH), 7.38 (t,1H, J¼5.7 Hz, NH), 7.57e7.67 (m, 2H, ArH), 8.12 (s,1H,
Acknowledgements
H-2-benzimidazolyl). 13C NMR (100 MHz, CDCl3):
d 42.2 (CH2NH),
The authors wish to thank EGIDE (the Gilibert programme) for
a fellowship (G.V.).
44.5 (CH2O), 60.1 (CH2OH), 72.6 (CHN), 110.4, 114.8 (C]CH2), 119.2,
121.4, 122.3, 134.1 (C]CH), 135.3, 143.1, 144.4, 155.4 (C]O).
References and notes
4.2.10. Methyl
{[3-(1H-benzimidazol-1-yl)-2-hydroxypropyl]sul-
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