An expeditious synthesis of 1-substituted and cyclic taurines

Article abstract of DOI:10.1055/s-2005-869994

A series of 1-substituted taurines, including optically active taurines, were synthesized expeditiously from epoxides via episulfidation with potassium sulfocyanate, ring-opening with dibenzylamine, followed by oxidation with performic acid, and hydrogenolysis in the presence of palladium hydroxide on carbon powder. This method was also used for the synthesis of trans-cyclic taurines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869994

2122
PAPER
An Expeditious Synthesis of 1-Substituted and Cyclic Taurines
Synthesis
i
of 1-Su
a
bstituted an
x
d
Cyclic
T
a
i
urine
s
ng Huang, Fei Wang, Da-Ming Du, Jiaxi Xu*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Department of Chemical Biology,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
Fax +86(10)62751708; E-mail: jxxu@pku.edu.cn
Received 20 January 2005; revised 7 April 2005
2-Substituted taurines have been synthesized effectively
Abstract: A series of 1-substituted taurines, including optically ac-
via sulfite displacement of the methanesulfonates of the
tive taurines, were synthesized expeditiously from epoxides via
vicinal amino alcohols,8–13 the peroxy acid oxidation of
episulfidation with potassium sulfocyanate, ring-opening with
the thioacetates of vicinal amino primary alcohols,14–19
dibenzylamine, followed by oxidation with performic acid, and hy-
drogenolysis in the presence of palladium hydroxide on carbon aminosulfonation of alkenes,20 and sulfite ring-opening of
aziridines.21 However, there has been little attention paid
powder. This method was also used for the synthesis of trans-cyclic
to the synthesis of 1-substituted taurines.16,19,22,23 Very re-
taurines.
Key words: amino acid, aminoalkanesulfonic acid, epoxide,
episulfide, synthesis, taurine
cently, we reported an effective and general method for
the preparation of N-protected 1-substituted and cis-1,2-
disubstituted taurines.23,24 Herein, we describe a short
route to the synthesis of 1-substituted and cyclic taurines
During the last two decades aminoalkylphosphonic acid from olefins and epoxides.
and aminoalkanesulfonic acid derivatives have been
In our on-going research concerning the synthesis of
widely used as enzyme inhibitors and haptens in the de-
velopment of catalytic antibodies because of their struc-
tural properties.1–5 Several 2-aminoalkanesulfonic acids
have also been found in many mammalian tissues and
they are involved in various and important physiological
processes.6 It has been demonstrated clearly that taurine
and its cyclic analogues show different effects on ATP-
dependent calcium ion uptake and protein phosphoryla-
tion in rat retina.7 Thus, it has become very important to
develop efficient methods to synthesize structurally di-
verse aminoalkanesulfonic acids for the investigation of
biological activities and structure-activity relationships.
b-Aminoalkanesulfonic acids are very important sulfur
analogues of naturally occurring amino acids because a-
aminoalkanesulfonic acids and their derivatives are unsta-
ble.5 There are three types of structural analogues of nat-
urally occurring amino acids of b-aminoalkanesulfonic
acids, which include 1-substituted taurines, 2-substituted
taurines, and 1,2-disubstituted taurines (Figure 1).
structurally diverse sulfur analogues of naturally occur-
ring amino acids we attempted to prepare 1-substituted
and cyclic taurines effectively. It is well known that vici-
nal amino primary alcohols have been used as important
key intermediates for synthesizing 2-substituted tau-
rines.8,9,14–19 In most cases, their hydroxyl group was con-
verted to a thiol or its ester, which after peroxy acid
oxidation gave rise to 2-substituted taurines. Sulfite ring-
opening of aziridines has been utilized as an expeditious
method for the synthesis of 2-substituted taurines due to
sulfite attack on the less bulky carbon atom of the aziri-
dine rings.21 Episulfides should be useful starting materi-
als for the synthesis of 1-substituted taurines because they
can be prepared from commercially available terminal
olefins or 1,2-epoxyalkanes efficiently.25,26 Ammonia or
amine ring-opening of 1,2-episulfides would generate vic-
inal amino secondary thiols, subsequent peroxy acid oxi-
dation would afford 1-substituted taurines.
Commercially available or self-prepared 1,2-alkanepox-
ides 1 were converted to the corresponding episulfides 2
with potassium sulfocyanate in the absence or presence of
silica gel in acceptable and satisfactory yields according
to the literature.26 Firstly, ammonia and primary amines,
including methylamine, benzylamine, and aniline, were
subjected to the ring-opening reactions of 1,2-episulfides
to generate vicinal amino secondary thiols.27 The results
indicated that complex mixtures were always obtained in
the reactions. In most cases, polymerization occurred as
described in the literature even when episulfides were
added dropwise into a large excess of ammonia and pri-
mary amine.25 However, the desired ring-opened prod-
ucts, vicinal amino secondary mercaptans 3aa and 3bb,
were obtained in good yields for secondary amines, in-
cluding linear diethylamine and cyclic piperidine.27 After
crude purification the mercaptans were directly subjected
SO3H
SO3H
H2N
H2N
R
taurine
R
1-substituted taurine
R1
SO3H
SO3H
H2N
H2N
R2
2-substituted taurine
1,2-disubstituted taurine
Figure 1 Taurine and substituted taurines
SYNTHESIS 2005, No. 13, pp 2122–2128
x
x.
x
x
.
2
0
0
5
Advanced online publication: 13.07.2005
DOI: 10.1055/s-2005-869994; Art ID: F01305SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 1-Substituted and Cyclic Taurines
2123
to further oxidation. It is not easy to afford very pure mer- yields (Scheme 1). It is interesting to note that the benzyl
captans because they were easily oxidized to disulfides in group attached to the oxygen atom in 1-benzyloxymethyl
air. Both the mercaptans and the disulfide could be oxi- taurine 5d is not removed in the presence of palladium hy-
dized to N,N-disubstituted 1-substituted taurines with per- droxide on carbon powder. Compound 5d was further
oxy acid. After the peroxy acid oxidation of N,N- treated under an atmosphere of hydrogen in the presence
dialkylamino mercaptan hydrochlorides,23 N,N-disubsti- of palladium on carbon powder to yield the desired 1-hy-
tuted 1-substituted taurines 4aa and 4bb were obtained in droxymethyl taurine 6d in good yield (Scheme 1). The re-
good yields (Scheme 1).
sults indicated that palladium hydroxide on carbon
powder chemoselectively removes the benzyl group from
nitrogen, but it cannot effect the removal of the benzyl
group attached to an oxygen atom. However, palladium
on carbon powder does not show such chemoselectivity.
A series of 1-substituted taurines with a diverse range of
functional groups were synthesized by this method.
SH
SO3H
NR1
H2O2, HCO2H
HCl
NR1
2
2
R
R
3aa, 3bb
4aa, 4bb
aa: R = Me, R1 = –(CH2)5-; bb: R = PhOCH2, R1 = Et
HNR1
2
For styrene episulfide 2f, an aromatic-substituted episul-
fide; its ring-opening reaction with dibenzylamine pro-
duced a mixture of vicinal amino secondary thiol 3f and
primary thiol 3¢f in a ratio near 1:1. No regioselectivity
was observed although regiospecific ring-opened prod-
ucts were obtained for alkyl-substituted episulfides 2a–e.
It is similar to the ring-opening reactions of styrene
oxide28 and 2-phenylaziridine29 with nucleophiles. Thus, a
mixture of 1- and 2-phenyl taurines was obtained from
styrene sulfide 2f. This seems to indicate that 1-aryltau-
rines cannot be prepared by this method.
SH
H2O2, HCO2H
HCl
Bn2NH
KSCN
O
S
NBn2
R
R
R
R
2a–f
3a–e
1a–f
SO3H
H2, Pd/C
MeOH
SO3H
SO3H
NH2
H2, Pd(OH)2/C
MeOH
HO
NH2
NBn2
R
6d from 5d
5a-e
4a-e
1–5: a: R = Me; b: R = PhOCH2; c: R = n -Hex; d: R = BnOCH2; f: R = Ph
1–4: e: R = Bn2NCH2; 5: e: R = H2NCH2
NBn2
SH
KSCN
Bn2NH
H2O2, HCO2H
HCl
O
S
Previously, cis-2-(benzyloxycarbonyl)aminocycloalkane-
sulfonic acids were prepared from cycloalkene oxides.23
After the deprotection of the benzyloxycarbonyl group,
cis-2-aminocycloalkanesulfonic acids could be obtained.
cis-2-Aminocyclohexanesulfonic acid was also prepared
from the hydrogenation of aniline-2-sulfonic acid.30
trans-2-Aminocyclohexanesulfonic acid was prepared by
the amino-sulfonation of cyclohexene.20,30 In a route sim-
ilar to the synthesis of 1-substituted taurines, trans-cyclic
aminoalkanesulfonic acids could also be prepared from
cycloalkene oxides. Cyclohexene oxide 1g was converted
to cyclohexene sulfide 2g, which underwent a ring-open-
ing reaction with dibenzylamine to afford trans-2-N,N-
dibenzylamino-1-cyclohexanethiol (3g). The thiol was
converted to its hydrochloride and subsequenetly oxi-
dized with performic acid to afford trans-2-N,N-dibenzyl-
aminocyclohexanesulfonic acid (4g). It was hydro-
genolyzed in methanol under an atmosphere of hydrogen
in the presence of palladium hydroxide on carbon powder
to afford trans-2-aminocyclohexanesulfonic acid (5g) in a
good yield (Scheme 2).
+
SH
NBn2
Ph
Ph
Ph
Ph
Ph
1f
3'f
3f
2f
SO3H
NBn2
NH2
H2, Pd(OH)2/C
SO3H
NH2
+
NBn2
SO3H
+
SO3H
Ph
Ph
Ph
MeOH
4f
4'f
5'f
5f
Scheme 1 Synthesis of 1-substituted taurines
If N,N-dialkylamino mercaptans were directly oxidized
by peroxy acid, N,N-disubstituted 1-substituted taurines
were obtained in low yields (around 40%) due to the for-
mation of N-oxide derivatives of N,N-disubstituted 1-sub-
stituted taurines. In order to synthesize N-nonsubstituted
1-substituted taurines 5, dibenzylamine was chosen and
used as a secondary amine. After the dibenzylamine ring-
opening of episulfides 2 the desired vicinal N,N-dibenzyl
amino secondary thiols 3 were obtained in satisfactory
yields. They were dissolved in formic acid and treated
with concentrated hydrochloric acid to form their hydro-
chlorides; oxidation with performic acid afforded N,N-
dibenzyl 1-substituted taurines 4. Firstly, N,N-dibenzyl
derivatives 4 were hydrogenolyzed in methanol under an
atmosphere of hydrogen in the presence of palladium on
carbon powder. The results indicated that the benzyl
group on the nitrogen atom cannot be removed complete-
ly, a mixture of N,N-dibenzyl, N-monobenzyl, and N-non-
benzyl derivatives were obtained even after a reaction
time of several days. Finally, they were hydrogenolyzed
in methanol under an atmosphere of hydrogen in the pres-
ence of palladium hydroxide on carbon powder to yield
the desired 1-substituted taurines 5 in good to excellent
S
Bn2N
SH
O
H2O2, HCO2H
HCl
KSCN
Bn2NH
1g
2g
trans-( )-3g
Bn2N
SO3H
H2N
SO3H
H2, Pd(OH)2
MeOH
trans-( )-4g
trans-( )-5g
Scheme 2 Synthesis of trans-cyclic taurine
Synthesis 2005, No. 13, 2122–2128 © Thieme Stuttgart · New York

2124
J. Huang et al.
PAPER
The current synthetic method was also applied to the prep- portant sulfur analogues of naturally occurring amino ac-
aration of optically active 1-substituted taurines ids. The current method can also be used to prepare N,N-
(Scheme 3). (R)-Glycidol (98%ee from Aldrich) was con- disubstituted 1-substituted taurines.
verted to (S)-benzyl glycidyl ether (S)-1d in 69% yield
and 98% ee via benzylation,31 and (S)-glycidyl phenyl
Melting points were measured on a Yanaco MP-500 melting point
apparatus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded on Varian Mercury 200 (200 MHz), Mercury Plus 300
(300 MHz), or Bruker ARX400 (400 MHz) spectrometer in CDCl3
with TMS as an internal standard, in D2O, in DMSO-d6, or in formic
acid. Mass spectra were obtained on a VG-ZAB-HS mass spectro-
meter or a Brucker ESQUIRE-LCTM ESI ion trap mass spectrome-
ter. HRMS data was carried out on a Brucker APEX 47e Fourier
transform ion cyclotron resonance (FTICR) mass spectrometer. IR
spectra were determined on a Nicolet AVATAR 330 FT-IR spec-
trometer. CHN analyses were recorded on an Elementar Vario EL
analyzer. Optical rotations were measured on a Perkin-Elmer Model
341LC polarimeter with a thermally jacketed 10 cm cell (concentra-
tion c given as g/100 mL). HPLC analyses were performed on an
HP1100 HPLC equipment. The ee values were determined by
HPLC analysis with chiralcel AD, OB, or OD-H columns
(4.6 × 250 mm) using a mixture of hexane–i-PrOH as eluent at
monitoring wave 220 nm. Petroleum ether used had a boiling range
of 30–60 °C. Episulfides 2 were prepared from epoxides 1 with po-
tassium sulfocyanate in the presence or absence of silica gel in ac-
ceptable and satisfactory yields according to the literature method.26
The analytical data of all known compounds are identical to those
reported.20,22,32,34–36
ether (S)-1b in 58% total yield and 93% ee via tosylation
and displacement with sodium phenolate.32 (S)-Glycidyl
phenyl ether (S)-1b was obtained in relatively low optical
purity because the displacement of sodium phenolate with
(S)-glycidyl tosylate could result in both SN2 and SN2¢
pathways (ratio 97:3 in DMF32). Both optically active gly-
cidyl ethers (S)-1b and (S)-1d were further converted to
episulfides (R)-2b in 49% yield and 91% ee, and (R)-2d in
64% yield and 96% ee, respectively, with potassium sul-
focyanate. It was found that their optical purities de-
creased slightly, which is in agreement with a previous
report that a complete Walden inversion occurred during
the conversion.33 Optically active N,N-dibenzylamino-
alkylmercaptans (S)-3b and (S)-3d were obtained via the
ring-opening reaction of episulfides (R)-2b and (R)-2d
with dibenzylamine without loss of optical activity on the
basis of HPLC analysis on a chiral column. After oxida-
tion and hydrogenolysis, optically active 1-substituted
taurines (S)-5b, (S)-5d, and (S)-6d were obtained in satis-
factory yields. Optical activities should not decrease dur-
ing oxidation and hydrogenolysis because the reactions do
not affect the chiral centers. This indicated that the current
method is an efficient synthesis of optically active 1-sub-
stituted taurines by using optically active epoxides as
starting materials with only a slight loss of optical activity
during the transformation of an epoxide to the correspond-
ing episulfide.
(S)-Glycidyl Phenyl Ether (S)-1b32
Prepared from (R)-glycidol by a known method.
Yield: 58%; colorless oil; Rf 0.39 (petroleum ether–EtOAc, 20:1).
93% ee; determined by HPLC with Chiralcel OD-H column (hex-
ane–i-PrOH, 90:10), flow rate 0.8 mL/min; tRminor 9.10 min,
tRmajor 13.51 min.
[a]D20 +12.4 (c 1.58, EtOH) {Lit.32 [a]D25 +14.1 (c 2.36, MeOH)}.
(S)-Benzyl Glycidyl Ether (S)-1d31
Prepared from (R)-glycidol by a known method.
1) TsCl, Et3N; 2) PhOH, NaH for (S)-1b
or BnBr, NaH, THF for (S)-1d
O
HO
(R)
Yield: 69%; colorless oil; Rf 0.20 (petroleum ether–EtOAc, 20:1).
Bn2NH
S
KSCN
O
O
O
98% ee; determined by HPLC with Chiralcel OD-H column (hex-
ane–i-PrOH, 90:10), flow rate 0.8 mL/min; tRmajor 8.78 min,
tRminor 9.36 min.
R
R
R
(S)-1b,d
SH
(R)-2b,d
SO3H
NBn2
[a]D20 +6.78 (c 1.23, EtOH) {Lit.34 [a]D20 +7.82 (c 0.40, EtOH)}.
H2O2, HCO2H
HCl
O
NBn2
O
R
(R)-2-Phenoxymethylepisulfide (2b)26
Prepared from epoxide (S)-1b and potassium sulfocyanate by a
known method.
(S)-3b,d
(S)-4b,d
SO3H
NH2
SO3H
NH2
H2, Pd(OH)2/C
MeOH
H2, Pd/C
MeOH
HO
O
R
Yield: 64%; colorless oil; Rf 0.45 (petroleum ether–EtOAc, 20:1).
(S)-5b,d
1–5: b: R = Ph; d: R = Bn
(S)-6d from (S)-5d
91% ee; determined by HPLC with Chiralcel OD column (hexane–
i-PrOH, 90:10), flow rate 0.8 mL/min; tRmajor 6.84 min, tRminor 8.29
min.
Scheme 3 Synthesis of optically active 1-substituted taurines
[a]D20 –15.0 (c 1.25, CHCl3) {Lit.35 [a]23D +15.9 (c 1.0, CHCl3)};
the configuration of 2b in the literature is wrong, it should be S be-
cause a Walden inversion occurred during the transformation; based
on the mechanism proposed in the literature33 and our current re-
sults.
In summary, 1-substituted and trans-cyclic taurines were
synthesized expeditiously from epoxides via episulfida-
tion with potassium sulfocyanate, ring-opening reaction
with dibenzylamine, followed by the oxidation with per-
oxyformic acid, and hydrogenolysis in the presence of
palladium hydroxide on carbon powder. This synthetic
route can be used as a general method to synthesize race-
mic and optically active 1-substituted taurines and trans-
cyclic 2-aminocycloalkanesulfonic acids, which are im-
1H NMR (200 MHz, CDCl3): d = 7.34–6.89 (m, 5 H, Ph), 4.22 (dd,
J = 5.6, 10.3 Hz, 1 H, OCHH), 3.90 (dd, J = 6.8, 10.3 Hz, 1 H,
OCHH), 3.27 (dddd, J = 5.0, 5.2, 5.6, 6.8 Hz, 1 H, SCH), 2.61 (dd,
J = 1.0, 5.0 Hz, 1 H, SCHH), 2.33 (dd, J = 1.0, 5.2 Hz, 1 H, SCHH).
13C NMR (50 MHz, CDCl3): d = 158.4, 129.6, 121.3, 114.6, 72.5,
31.3, 24.0.
Synthesis 2005, No. 13, 2122–2128 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Substituted and Cyclic Taurines
2125
(R)-2-Benzyloxymethylepisulfide (2d)
Prepared from epoxide (S)-1d and potassium sulfocyanate by a
known method.
90% ee; determined by HPLC with Chiralcel AD column (hexane–
i-PrOH, 99:1), flow rate 0.8 mL/min; tRmajor 8.17 min, tRminor 9.32
min.
Yield: 49%; colorless oil; Rf 0.38 (petroleum ether–EtOAc, 20:1).
[a]D20 +4.2 (c 1.10, CHCl3).
96% ee; determined by HPLC with Chiralcel OB column (hexane–
i-PrOH, 95:5), flow rate 0.8 mL/min; tRminor 12.01 min, tRmajor 13.03
min.
1H NMR (200 MHz, CDCl3): d = 7.38–6.78 (m, 15 H, Ph), 4.07 (dd,
J = 4.8, 9.2 Hz, 1 H, OCHH), 3.91 (dd, J = 3.2, 9.2 Hz, 1 H,
OCHH), 3.61 (s, 4 H, 2 × NCH2), 3.41 (dddd, J = 3.2, 4.8, 7.2, 7.6
Hz, 1 H, SCH), 2.85 (dd, J = 7.6, 13.0 Hz, 1 H, NCHH), 2.59 (dd,
J = 7.2, 13.0 Hz, 1 H, NCHH), 2.02 (br s, 1 H, SH).
[a]D20 –9.05 (c 1.31, CHCl3) {Lit.36 [a]D 11 (c 10, CHCl3) for (S)-
2d}.
13C NMR (50 MHz, CDCl3): d = 158.5, 138.9, 129.4, 129.0, 128.3,
127.2, 121.0, 114.6, 70.7, 58.8, 57.6, 37.9.
1H NMR (200 MHz, CDCl3): d = 7.37–7.28 (m, 5 H, Ph), 4.59 (s, 2
H, CH2O), 3.70 (dd, J = 5.8, 10.6 Hz, 1 H, OCHH), 3.49 (dd, J =
6.8, 10.6 Hz, 1 H, OCHH), 3.11 (dddd, J = 5.6, 5.8, 6.2, 6.8, Hz, 1
H, SCH), 2.52 (dd, J = 1.4, 6.2 Hz, 1 H, SCHH), 2.21 (dd, J = 1.4,
5.6 Hz, 1 H, SCHH).
1-N,N-Dibenzylamino-2-octylmercaptan (3c)
Yield: 49%; colorless oil; Rf 0.51 (petroleum ether–EtOAc, 30:1).
1H NMR (300 MHz, CDCl3): d = 7.37–7.24 (m, 10 H, Ph), 3.65 (d,
J = 13.5 Hz, 2 H, 2 × NCHH), 3.46 (d, J = 13.5 Hz, 2 H, 2 ×
NCHH), 2.88 (quintet, J = 5.7 Hz, 1 H, SCH), 2.50 (dd, J = 0.9, 6.0
Hz, 1 H, NCHH), 2.15 (dd, J = 0.9, 5.4 Hz, 1 H, NCHH), 1.85–1.77
(m, 1 H, CHH), 1.56–1.42 (m, 3 H, CH2CH2), 1.40–1.22 (m, 6 H,
3 × CH2), 0.89 (t, J = 6.6 Hz, 3 H, CH3).
13C NMR (50 MHz, CDCl3): d = 137.8, 128.4, 127.77, 127.73, 76.6,
73.1, 32.1, 23.6.
Vicinal N,N-Dialkylaminoalkylmercaptans 3; General Proce-
dure
To a rapidly stirred amine (6 mmol) in benzene–EtOH (6 mL, 9:1)
was added dropwise (the flask was pressurized by a rubber capsule
and the reagent was added by using an injector) to a solution of al-
kene sulfide (3 mmol) in the same solvent (3 mL) at 60 °C over 1 h.
The reaction was then stirred at 60 °C for 24 h when TLC indicated
the complete disappearance of thiirane. After removal of the solvent
under reduced pressure, crude purification of the residue by column
chromatography (silica gel; petroleum ether–EtOAc, 20:1) afforded
amino alkylmercaptan.
13C NMR (75.5 MHz, CDCl3): d = 130.1, 129.0, 128.2, 127.0, 58.6,
36.6, 36.0, 31.7, 29.3, 28.9, 25.6, 22.6, 14.0.
1-Benzyloxy-3-N,N-dibenzylamino-2-propylmercaptan (3d)
Yield: 82%; colorless oil; Rf 0.36 (petroleum ether–EtOAc, 20:1).
1H NMR (200 MHz, CDCl3): d = 7.29 (s, 15 H, Ph), 4.43 (s, 2 H,
OCH2), 3.60 (d, J = 13.6 Hz, 2 H, 2 × NCHH), 3.57 (dd, J = 4.8, 9.6
Hz, 1 H, OCHH), 3.49 (d, J = 13.6 Hz, 2 H, 2 × NCHH), 3.39 (dd,
J = 6.6, 9.6 Hz, 1 H, OCHH), 3.24 (dddd, J = 4.8, 6.6, 12.8, 13.0
Hz, 1 H, SCH), 2.72 (dd, J = 7.7, 13.0 Hz, 1 H, NCHH), 2.49 (dd,
J = 7.7, 12.8 Hz, 1 H, NCHH).
1-Piperidino-2-propylmercaptan (3aa)
Yield: 69%; colorless oil; Rf 0.48 (petroleum ether–acetone, 5:1).
The product was oxidized directly without purification.
13C NMR (50 MHz, CDCl3): d = 138.9, 138.1, 129.0, 128.3, 128.2,
127.6, 127.0, 73.1, 72.9, 58.5, 57.7, 38.5.
1-N,N-Diethylamino-3-phenoxy-2-propylmercaptan (3bb)
Yield: 82%; colorless oil; Rf 0.47 (petroleum ether–acetone, 10:1).
(S)-1-Benzyloxy-3-N,N-dibenzylamino-2-propylmercaptan
[(S)-3d]
Yield: 78%; colorless oil; Rf 0.36 (petroleum ether–EtOAc, 20:1).
1H NMR (200 MHz, CDCl3): d = 7.80–6.88 (m, 5 H, Ph), 4.24–4.19
(m, 2 H, OCH2), 3.18 (m, 1 H, SCH), 2.60 (br s, 1 H, SH), 2.50 (q,
J = 6.8 Hz, 4 H, 2 × NCH2), 0.97 (t, J = 6.8 Hz, 6 H, 2 × CH3).
96% ee; determined by HPLC with Chiralcel OD column (hexane–
i-PrOH, 99.7:0.3), flow rate 0.8 mL/min, tRmajor 29.6 min,
tRminor 32.3 min.
13C NMR (50 MHz, CDCl3): d = 158.5, 129.3, 120.8, 114.6, 67.5,
54.5, 50.2, 47.5, 11.8.
[a]D20 +13.1 (c 1.17, CHCl3).
1-N,N-Dibenzylamino-2-propylmercaptan (3a)
Yield: 66%; colorless oil; Rf 0.53 (petroleum ether–EtOAc, 10:1).
1H NMR (300 MHz, CDCl3): d = 7.37–7.20 (m, 15 H, Ph), 4.45 (s,
2 H, OCH2), 3.60 (d, J = 13.6 Hz, 2 H, 2 × NCHH), 3.57 (dd, J =
4.8, 9.6 Hz, 1 H, OCHH), 3.49 (d, J = 13.6 Hz, 2 H, 2 × NCHH),
3.40 (dd, J = 6.3, 9.6 Hz, 1 H, OCHH), 3.26 (dddd, J = 4.8, 6.3, 6.9,
7.8 Hz, 1 H, SCH), 2.73 (dd, J = 6.9, 13.0 Hz, 1 H, NCHH), 2.50
(dd, J = 7.8, 13.0 Hz, 1 H, NCHH), 2.05 (br s, 1 H, SH).
1H NMR (200 MHz, CDCl3): d = 7.40–7.21 (m, 10 H, Ph), 3.64 (d,
J = 13.2 Hz, 2 H, 2 × NCHH), 3.50 (d, J = 13.2 Hz, 2 H, 2 ×
NCHH), 3.14 (tq, J = 7.2, 6.8 Hz, 1 H, SCH), 2.48 (d, J = 7.2 Hz, 2
H, CH2), 2.01 (br s,1 H, SH), 1.27 (d, J = 6.8 Hz, 3 H, CH3).
13C NMR (75.5 MHz, CDCl3): d = 130.7, 130.4, 129.6, 129.3,
128.6, 128.2, 65.6, 59.6, 31.4, 21.5.
13C NMR (75.5 MHz, CDCl3): d = 138.9, 138.0, 129.0, 128.3,
128.2, 127.61, 127.59, 127.0, 73.2, 73.0, 58.6, 57.8, 38.6.
1-N,N-Dibenzylamino-3-phenoxy-2-propylmercaptan (3b)
Yield: 75%; colorless oil; Rf 0.43 (petroleum ether–EtOAc, 20:1).
1,3-Bis(N,N-dibenzylamino)-2-propylmercaptan (3e)
Yield: 75%; colorless oil; Rf 0.43 (petroleum ether–EtOAc, 20:1).
1H NMR (200 MHz, CDCl3): d = 7.45–6.80 (m, 15 H, Ph), 4.08 (dd,
J = 5.2, 9.5 Hz, 1 H, OCHH), 3.91 (dd, J = 6.2, 9.5 Hz, 1 H,
OCHH), 3.62 (s, 4 H, 2 × NCHH), 3.45 (dddd, J = 5.2, 6.2, 7.2, 7.6
Hz, 1 H, SCH), 2.86 (dd, J = 7.6, 13.2 Hz, 1 H, NCHH), 2.60 (dd,
J = 7.2, 13.2 Hz, 1 H, NCHH), 1.59 (br s, 1 H, SH).
1H NMR (200 MHz, CDCl3): d = 7.41–7.10 (m, 20 H, Ph), 3.71 (d,
J = 3.4 Hz, 1 H, SH), 3.59 (d, J = 13.8 Hz, 2 H, 2 × NCHH), 3.41
(d, J = 13.8 Hz, 2 H, 2 × NCHH), 3.00–2.78 (m, 1 H, SCH), 2.63
(dd, J = 5.0, 12.8 Hz, 2 H, 2 × NCHH), 2.34 (dd, J = 8.8, 12.8 Hz,
2 H, 2 × NCHH).
13C NMR (50 MHz, CDCl3): d = 158.5, 138.9, 129.5, 129.1, 128.3,
127.2, 121.0, 114.6, 70.8, 58.8, 57.6, 37.9.
13C NMR (50 MHz, CDCl3): d = 138.9, 129.1, 128.7, 128.3, 128.2,
127.0, 59.2, 58.5, 58.4.
(S)-1-N,N-Dibenzylamino-3-phenoxy-2-propylmercaptan [(S)-
3b]
Colorless oil; yield: 78%; Rf 0.43 (petroleum ether–EtOAc, 20:1).
trans-2-N,N-Dibenzylaminocyclohexylmercaptan (3g)
Yield: 18%; colorless oil; Rf 0.33 (petroleum ether–EtOAc, 20:1).
The product was oxidized directly without further purification.
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N,N-Disubstituted Aminoalkanesulfonic Acids 4; General Pro-
cedure
13C NMR (75.5 MHz, HCO2H): d =130.2, 130.1, 129.4, 129.1,
128.3, 128.1, 58.6, 57.4, 53.6, 49.4, 11.9.
To a performic acid solution, prepared by mixing and stirring H2O2
(30%; 1.2 mL) and HCO2H (88%; 12 mL) at r.t. for 1 h and cooled
in an ice bath, was added amino mercaptan (2 mmol) in a mixture
of HCl (36%; 1 mL) and HCO2H (88%; 2.7 mL) dropwise, keeping
the temperature at 0 °C. The resulting mixture was stirred at 0 °C
for an additional 2 h and at r.t. for 2 d. After removal of the solvent,
the residue was purified by column chromatography (CH2Cl2–
MeOH, 20:1). Recrystallization (EtOH) gave 1-substituted 2-di-
alkylaminoethanesulfonic acid as colorless crystals.
MS (ESI): m/z = 412 (MH)+.
Anal. Calcd for C23H25NO4S·1.25H2O (434.03): C, 63.65; H, 6.39;
N, 3.23. Found: C, 63.41; H, 6.12; N, 3.09.
(S)-1-N,N-Dibenzylamino-3-phenoxypropane-2-sulfonic Acid
[(S)-4b]
Yield: 87%; colorless crystal; mp 210–212 °C; Rf 0.43 (CH2Cl2–
MeOH, 10:1).
90% ee.
1-Piperidinopropane-2-sulfonic Acid (4aa)
Yield: 88%; colorless crystals; mp 211–213 °C (from the episul-
fide); Rf 0.47 (CH2Cl2–MeOH, 5:1).
[a]D20 +15.7 (c 1.05, 88% HCO2H).
IR (KBr): 1244.7 (S=O), 1166.9 (S=O), 697.6 (SO) cm–1.
1H NMR (200 MHz, CDCl3): d = 10.32 (br s, 1 H, SO3H), 7.62–6.71
(m, 15 H, Ph), 4.78–4.36 (m, 3 H, CHCH2), 4.36–4.17 (m, 1 H,
OCHH), 4.03–3.88 (m, 1 H, OCHH), 3.61 (s, 4 H, 2 × NCH2).
IR (KBr): 1239.8 (S=O), 1154.1 (S=O), 698.7 (SO) cm–1.
1H NMR (200 MHz, CDCl3): d = 9.18 (br s, 1 H, SO3H), 3.91 (dd,
J = 12.0, 14.0 Hz, 2 H, 2 × NCHH), 3.54–3.41 (m, 2 H, 2 × NCHH),
2.98–2.63 (m, 3 H, CH, NCH2), 2.18–1.78 (m, 4 H, 2 × CH2), 1.60–
1.28 (m, 2 H, CH2), 1.39 (d, J = 6.0 Hz, 3 H, CH3).
13C NMR (75.5 MHz, HCO2H): d = 130.2, 130.1, 129.4, 129.1,
128.3, 128.1, 58.6, 57.4, 53.6, 49.4, 11.9.
MS (ESI): m/z = 412 (MH)+.
13C NMR (50 MHz, HCO2H): d = 57.6, 55.4, 52.4, 48.8, 22.3, 22.2,
20.3, 12.1.
Anal. Calcd for C23H25NO4S·1.25H2O (434.03): C, 63.65; H, 6.39;
N, 3.23. Found: C, 63.41; H, 6.12; N, 3.09.
MS (ESI): m/z = 208 (MH)+.
Anal. Calcd for C8H17NO3S·0.75H2O (220.81): C, 43.52; H, 8.45;
N, 6.34. Found: C, 43.40; H, 8.39; N, 6.19.
1-N,N-Dibenzylaminooctane-2-sulfonic Acid (4c)
Yield: 56%; colorless crystals; mp 230–232 °C; Rf 0.40 (CH2Cl2–
MeOH, 10:1).
1-N,N-Diethylamino-3-phenoxypropane-2-sulfonic Acid (4bb)
Yield: 93%; colorless crystals, mp 177–179 °C; Rf 0.57 (CH2Cl2–
MeOH, 10:1).
IR (KBr): 1291.9 (S=O), 1145.5 (S=O), 725.9 (SO) cm–1.
1H NMR (300 MHz, CDCl3): d = 10.72 (br s, 1 H, SO3H), 7.57–7.41
(m, 10 H, Ph), 4.60–4.43 (m, 3 H, NCHH, 2 × CHHN), 4.31 (dd,
J = 5.1, 13.2 Hz, 1 H, CHHN), 3.60–3.45 (m, 2 H, 2 × CHHN), 2.64
(m, 1 H, CH), 2.04 (m, 1 H, CHH), 1.41–1.28 (m, 1 H, CHH), 1.28–
1.10 (m, 8 H, 4 × CH2), 0.84 (t, J = 6.9 Hz, 3 H, CH3).
IR (KBr): 1291.2 (S=O), 1144.4 (S=O), 726.0 (SO) cm–1.
1H NMR (200 MHz, CDCl3): d = 8.88 (br s, 1 H, SO3H), 7.37–6.91
(m, 5 H, ArH), 4.70 (dd, J = 3.2, 9.2 Hz, 1 H, OCHH), 4.05 (t, J =
10.0 Hz, 1 H, OCHH), 3.71 (q, J = 7.2 Hz, 4 H, 2 × NCH2), 3.92–
3.20 (m, 3 H, CHCH2), 1.46 (t, J = 7.2 Hz, 6 H, 2 × CH3).
13C NMR (75.5 MHz, CDCl3): d = 130.6, 130.5, 130.2, 130.1,
129.6, 129.5, 129.2, 59.5, 56.5, 55.3, 54.4, 31.4, 29.1, 28.3, 26.6,
22.5, 14.0.
13C NMR (75.5 MHz, HCO2H): d = 151.6, 129.3, 127.7, 126.0,
122.5, 114.2, 65.6, 54.0, 50.5, 49.5, 47.8, 8.1, 7.1.
MS (Negative-ESI): m/z = 388 (M – H)–.
MS (Negative-ESI): m/z = 286 (M – H)–.
Anal. Calcd for C22H31NO3S (389.55): C, 67.83; H, 8.02; N, 3.60.
Found: C, 67.84; H, 7.96; N, 3.50.
Anal. Calcd for C13H21NO4S (287.38): C, 54.33; H, 7.37; N, 4.87.
Found: C, 54.25; H, 7.26; N, 4.87.
1-Benzyloxy-3-N,N-dibenzylaminopropane-2-sulfonic Acid
(4d)
Yield: 90%; colorless crystals, mp 164–166 °C; Rf 0.42 (CH2Cl2–
MeOH, 10:1).
1-N,N-Dibenzylaminopropane-2-sulfonic Acid (4a)
Yield: 89%; colorless crystals, mp 253–255 °C; Rf 0.39 (CH2Cl2–
MeOH, 5:1).
IR: 1233.4 (S=O), 1165.1 (S=O), 702.8 (SO) cm–1.
IR (KBr): 1246.7 (S=O), 1153.9 (S=O), 694.9 (SO) cm–1.
1H NMR (300 MHz, CDCl3): d = 10.01 (br s, 1 H, SO3H), 7.53–7.40
(m, 10 H, Ph), 4.72 (d, J = 12.2 Hz, 1 H, NCHH), 4.37 (d, J = 12.2
Hz, 1 H, NCHH), 3.28 (d, J = 11.0 Hz, 1 H, NCHH), 4.20 (d,
J = 11.0 Hz, 1 H, NCHH), 3.26–3.20 (m, 2 H, NCH2), 3.17–3.08
(m, 1 H, CH), 1.02 (d, J = 6.5 Hz, 3 H, CH3).
1H NMR (200 MHz, CDCl3): d =10.24 (br s, 1 H, SO3H), 7.60–7.18
(m, 15 H, Ph), 4.51 (s, 2 H, OCH2), 4.61–4.28 (m, 3 H, CHCH2),
4.28–4.03 (m, 2 H, NCH2), 3.55 (s, 4 H, 2 × NCH2).
13C NMR (50 MHz, HCO2H): d = 130.7, 130.4, 129.8, 129.4, 128.5,
128.3, 128.0, 127.1, 67.9, 58.7, 57.7, 53.9, 52.0.
13C NMR (75.5 MHz, HCO2H): d = 130.2, 130.1, 129.4, 129.1,
128.3, 128.1, 58.6, 57.4, 53.6, 49.4, 11.9.
MS (ESI): m/z = 426 (MH) +.
MS (Negative-ESI): m/z = 318 (M – H)–.
Anal. Calcd for C24H27NO4S·1.5H2O (452.56): C, 63.69; H, 6.68; N,
3.09. Found: C, 63.46; H, 6.17; N, 2.91.
Anal. Calcd for C17H21NO3S·0.5CH3OH (335.44): C, 62.66; H,
6.91; N, 4.18. Found: C, 62.78; H, 6.82; N, 4.02.
(S)-1-Benzyloxy-3-N,N-dibenzylaminopropane-2-sulfonic Acid
[(S)-4d]
Yield 84%; colorless crystals; mp 170–171.5 °C; Rf 0.42 (CH2Cl2–
MeOH, 10:1).
1-N,N-Dibenzylamino-3-phenoxypropane-2-sulfonic Acid (4b)
Yield: 81%; colorless crystals; mp 199–201 °C; Rf 0.43 (CH2Cl2–
MeOH, 10:1).
96% ee.
IR (KBr): 1244.7 (S=O), 1166.9 (S=O), 697.6 (SO) cm–1.
[a]D20 +26.5 (c 1.38, 88% HCO2H).
IR (KBr): 1246.7 (S=O), 1153.9 (S=O), 694.9 (SO) cm–1.
1H NMR (200 MHz, CDCl3): d = 10.34 (br s, 1 H, SO3H), 7.62–6.71
(m, 15 H, Ph), 4.78–4.36 (m, 3 H, CHCH2), 4.36–4.17 (m, 1 H,
OCHH), 4.03–3.88 (m, 1 H, OCHH), 3.61 (s, 4 H, 2 × NCH2).
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Synthesis of 1-Substituted and Cyclic Taurines
2127
1H NMR (200 MHz, CDCl3): d = 10.26 (br s, 1 H, SO3H), 7.60–7.18
(m, 15 H, Ph), 4.51 (s, 2 H, OCH2), 4.61–4.28 (m, 3 H, CHCH2),
4.28–4.03 (m, 2 H, NCH2), 3.55 (s, 4 H, 2 × NCH2).
MS (Negative-ESI): m/z = 230 (M – H)–.
Anal. Calcd for C9H13NO4S (231.27): C, 46.74; H, 5.67; N, 6.06.
Found: C, 46.78; H, 5.76; N, 5.86.
13C NMR (50 MHz, HCO2H): d = 130.7, 130.4, 129.8, 129.4, 128.5,
128.3, 128.0, 127.1, 67.9, 58.7, 57.7, 53.9, 52.0.
(S)-1-Amino-3-phenoxypropane-2-sulfonic Acid [(S)-5b]
Yield: 93%; colorless crystals; mp 329–331 °C.
MS (ESI): m/z = 426 (MH)+.
90% ee.
Anal. Calcd for C24H27NO4S·1.5H2O (452.56): C, 63.69; H, 6.68; N,
3.09. Found: C, 63.46; H, 6.17; N, 2.91.
[a]D20 +22.9 (c 0.85, 88% HCO2H).
IR (KBr): 3062 (br, NH, OH), 1248.9 (SO2), 1170 (SO2) cm–1.
1,3-Bis(N,N-dibenzylamino)propane-2-sulfonic Acid (4e)
Yield: 90%; colorless crystals; mp 210–212 °C; Rf 0.33 (CH2Cl2–
MeOH, 20:1).
1H NMR (300 MHz, D2O): d = 7.33–6.80 (m, 5 H, Ph), 4.39 (dd,
J = 3.9, 10.5 Hz, 1 H, OCHH), 4.17 (dd, J = 3.3, 7.2 Hz, 1 H,
NCHH), 3.56–3.39 (m, 3 H, OCHH, NCHH, CH).
IR (KBr): 1247.1 (S=O), 1168.2 (S=O), 695.6 (SO) cm–1.
13C NMR (75.5 MHz, D2O): d = 157.1, 128.7, 120.1, 113.6, 64.7,
54.3, 37.3.
1H NMR (300 MHz, CDCl3): d = 11.14 (br s, 1 H, SO3H), 7.60–7.40
(m, 20 H, ArH), 4.30 (br s, 8 H, 4 × NCH2), 3.80–3.57 (m, 4 H, 2 ×
NCH2), 3.44 (m, 1 H, CH).
MS (Negative-ESI): m/z = 230 (M – H)–.
13C NMR (75.5 MHz, CDCl3): d = 130.6, 130.5, 130.4, 130.0,
129.3, 128.6, 127.8, 59.0, 58.5, 50.6, 48.8.
Anal. Calcd for C9H13NO4S (231.27): C, 46.74; H, 5.67; N, 6.06.
Found: C, 46.78; H, 5.76; N, 5.86.
MS (ESI): m/z = 515 (MH)+.
1-Aminooctane-2-sulfonic Acid (5c)
Yield: 89%; colorless crystals; mp >360 °C.
Anal. Calcd for C31H34N2O3S·2H2O (550.71): C, 67.61; H, 6.95; N,
5.09. Found: C, 67.60; H, 6.69; N, 4.95.
IR (KBr): 3174.3 (br, NH, SOH), 1228.8 (SO2), 1167.5 (SO2) cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.70 (br s, 3 H, NH3 ), 2.98
+
trans-2-N,N-Dibenzylaminocyclohexanesulfonic Acid (4g)
Yield: 77%; colorless crystals; mp 285–287 °C; Rf 0.61 (CH2Cl2–
MeOH, 10:1).
(dd, J = 2.9, 13.1 Hz, 1 H, NCHH), 2.86 (dd, J = 9.6, 13.1 Hz, 1 H,
NCHH), 2.54 (m, 1 H, CH), 1.79–1.73 (m, 1 H, CHH), 1.43–1.30
(m, 1 H, CHH), 1.30–1.24 (m, 8 H, 4 × CH2), 0.88 (t, J = 6.6 Hz, 3
H, CH3).
IR (KBr): 1239.5 (S=O), 1214.5 (S=O), 699.2 (SO) cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.02 (br s, 1 H, SO3H), 7.64–
7.12 (m, 10 H, Ph), 4.86 (d, J = 12.8 Hz, 1 H, CHHN), 4.40 (dd,
J = 7.4, 14.0 Hz, 1 H, CHHN), 4.16 (dd, J = 2.9, 13.4 Hz, 1 H,
CHHN), 4.11 (dd, J = 9.1, 12.8 Hz, 1 H, CHHN), 3.42 (dt, J = 3.3,
11.4 Hz, 1 H, CH), 3.30 (dd, J = 4.0, 11.1 Hz, 1 H, CH), 2.30 (dd,
J = 2.56, 12.5 Hz, 1 H, CHH), 2.15 (m, 1 H, CHH), 1.87 (m, 1 H,
CHH), 1.71–1.60 (m, 2 H, CH2), 1.40–1.18 (m, 3 H, CH2).
13C NMR (100 MHz, DMSO-d6): d = 55.6, 39.5, 31.1, 28.6, 27.9,
26.2, 22.1, 14.0.
MS (ESI): m/z = 232 (M + Na)+.
Anal. Calcd for C8H19NO3S (209.31): C, 45.91; H, 9.15; N, 6.69.
Found: C, 45.96; H, 8.78; N, 6.70.
1-Amino-3-benzyloxypropane-2-sulfonic Acid (5d)
Yield: 83%; colorless crystals; mp 227–229 °C.
13C NMR (75.5 MHz, HCO2H): d = 130.3, 129.9, 129.7, 129.6,
129.2, 129.0, 128.6, 61.1, 56.1, 53.2, 26.0, 23.2, 22.8, 22.5.
IR (KBr): 3376.4, 3217.6 (br, NH, OH), 1269.8 (SO2), 1175 (SO2)
cm–1.
MS (Negative-ESI): m/z = 358 (M – H)–.
Anal. Calcd for C20H25NO3S (359.48): C, 66.82; H, 7.01; N, 3.90.
Found: C, 66.43; H, 7.10; N, 3.56.
1H NMR (300 MHz, D2O): d = 7.30 (s, 5 H, Ph), 4.17 (d, J = 13.2
Hz, 1 H, CHHO), 4.19 (d, J = 13.2 Hz, 1 H, CHHO), 3.85 (dd,
J = 4.2, 12.0 Hz, 1 H, CHHO), 3.56 (dd, J = 7.5, 12.0 Hz, 1 H,
CHHO), 3.30–3.24 (m, 2 H, NCH2), 3.24–3.12 (m, 1 H, CH).
1-Substituted 2-Aminoethanesulfonic Acids and 2-Aminocyclo-
alkanesulfonic Acid (Hydrogenolysis); General Procedure
N,N-Dibenzylaminoalkanesulfonic acid (0.50 mmol) was dissolved
in MeOH (10 mL), and Pd(OH)2/C (20%; 30 mg) was added. The
suspension was stirred under an atmosphere of hydrogen at 50 °C
overnight. MeOH (20 mL) was added to dissolve the precipitate.
The catalyst was removed by filtration through filter paper and was
washed with MeOH (2 × 5 mL). After evaporation of the solvent the
crude product was purified by recrystallization (MeOH) to afford
colorless crystals.
13C NMR (100 MHz, D2O): d = 130.6, 130.29, 130.28, 129.8, 59.7,
57.8, 51.8.
MS (Positive-ESI): m/z = 246 (MH)+.
Anal. Calcd for C10H15NO4S (245.30): C, 48.96; H, 6.16; N, 5.71.
Found: C, 48.96; H, 6.21; N, 5.64.
(S)-1-Amino-3-benzyloxypropane-2-sulfonic Acid [(S)-5d]
Yield 81%; colorless crystal; mp 239–241 °C.
1-Aminopropane-2-sulfonic Acid (5a)
Yield: 90%; colorless crystals; mp 286–288 °C (Lit.22 283–286 °C).
96% ee.
[a]D20 +28.9 (c 1.71, 88% HCO2H).
MS (ESI): m/z = 140 (MH)+.
IR (KBr): 3376.4, 3217.6 (br, NH, OH), 1269.8 (SO2), 1175 (SO2)
cm–1.
1-Amino-3-phenoxypropane-2-sulfonic Acid (5b)
Yield: 72%; colorless crystals; mp 307–309 °C.
1H NMR (300 MHz, D2O): d = 7.30 (s, 5 H, Ph), 4.17 (d, J = 13.2
Hz, 1 H, CHHO), 4.19 (d, J = 13.2 Hz, 1 H, CHHO), 3.85 (dd,
J = 4.2, 12.0 Hz, 1 H, CHHO), 3.56 (dd, J = 7.5, 12.0 Hz, 1 H,
CHHO), 3.30–3.24 (m, 2 H, NCH2), 3.24–3.12 (m, 1 H, CH).
IR (KBr): 3062 (br, NH, OH), 1248.9 (SO2), 1170 (SO2) cm–1.
1H NMR (300 MHz, D2O): d = 7.33–6.80 (m, 5 H, Ph), 4.39 (dd,
J = 3.9, 10.5 Hz, 1 H, OCHH), 4.17 (dd, J = 3.3, 7.2 Hz, 1 H,
NCHH), 3.56–3.39 (m, 3 H, OCHH, NCHH, CH).
13C NMR (100 MHz, D2O): d = 130.6, 130.29, 130.28, 129.8, 59.7,
57.8, 51.8.
13C NMR (75.5 MHz, D2O): d = 157.1, 128.7, 120.1, 113.6, 64.7,
54.3, 37.3.
MS (ESI, positive ion): m/z = 246 (MH)+.
Synthesis 2005, No. 13, 2122–2128 © Thieme Stuttgart · New York

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J. Huang et al.
PAPER
Anal. Calcd for C10H15NO4S (245.30): C, 48.96; H, 6.16; N, 5.71.
Found: C, 48.96; H, 6.21; N, 5.64.
References
(1) Pollack, S. J.; Hsiun, P.; Schultz, P. G. J. Am. Chem. Soc.
1989, 111, 5961.
1,3-Diaminopropane-2-sulfonic Acid (5e)
Yield: 92%; colorless crystals, mp 251–253 °C.
(2) Morgan, B. P.; Scholtz, J. M.; Ballinger, M. D.; Zipkin, I. D.;
Bartlett, P. A. J. Am. Chem. Soc. 1991, 113, 297.
(3) Xu, J. X.; Yu, L. Chin. J. Synth. Chem. 1999, 7, 153.
(4) Xu, J. X.; Fu, N. Y. J. Chem. Soc., Perkin Trans. 1 2001,
1223; and references cited therein.
(5) Xu, J. X. Chin. J. Org. Chem. 2003, 23, 1.
(6) Huxtable, R. J. Physiol. Rev. 1992, 72, 101.
(7) Liebowitz, S. M.; Lombardini, J. B.; Salva, P. S. Biochem.
Pharmacol. 1988, 37, 1303.
IR (KBr): 3152.4 (br, NH, SOH), 1191.8 (SO2), 1090.0 (SO2), 715.2
(SO) cm–1.
1H NMR (300 MHz, D2O): d = 3.41–3.31 (m, 1 H, CH), 3.29–3.19
(m, 4 H, 2 × CH2).
13C NMR (75.5 MHz, D2O): d = 56.1, 40.4.
MS (Negative-ESI): m/z = 153 (M – H)–.
Anal. Calcd for C3H10N2O3S·2H2O (190.22): C, 18.94; H, 7.42; N,
14.73. Found: C, 18.92; H, 7.58; N, 14.79.
(8) Higashiura, H.; Morino, H.; Matsuura, H.; Toyomaki, Y.;
Ienaga, K. J. Chem. Soc., Perkin Trans. 1 1989, 1479.
(9) Gude, M.; Piarulli, U.; Potenza, D.; Salom, B.; Gennari, C.
Tetrahedron Lett. 1996, 37, 8589.
(10) Braghiroli, D.; Di Bella, M. Tetrahedron: Asymmetry 1996,
7, 2145.
trans-2-Aminocyclohexanesulfonic Acid (5g)
Yield: 75%; colorless crystals; mp >360 °C (Lit.20 408 °C).
MS (ESI): m/z = 180 (MH)+.
(11) Braghiroli, D.; Avallone, R.; Di Bella, M. Tetrahedron:
Asymmetry 1997, 8, 2209.
1-Amino-3-hydroxypropane-2-sulfonic Acid (6d)
1-Amino-3-benzyloxypropane-2-sulfonic acid (5d; 0.20 g, 0.82
mmol) was dissolved in MeOH (15 mL), and Pd/C (20%, 20 mg)
was added. The suspension was stirred under an atmosphere of hy-
drogen at 50 °C for 1 d. The catalyst was removed by filtration
through filter paper and was washed with MeOH (2 × 5 mL). Re-
crystallization (MeOH–Et2O) of the residue gave 6d.
(12) Braghiroli, D.; Mussati, E.; Di Bella, M.; Saladini, M.
Tetrahedron: Asymmetry 1996, 7, 831.
(13) Braghiroli, D.; Di Bella, M. Tetrahedron Lett. 1996, 37,
7319.
(14) Higashiura, K.; Ienaga, K. J. Org. Chem. 1992, 57, 764.
(15) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J.
Tetrahedron Lett. 1992, 33, 6389.
(16) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J. J.
Org. Chem. 1995, 60, 5157.
Yield: 72%; colorless crystals, mp 165–167 °C.
IR (KBr): 3396.4, 3087.6 (br, NH, OH), 1211.7 (SO2), 1165.5 (SO2)
cm–1.
(17) Monnee, M. C. F.; Marijne, M. F.; Brouwer, A. J.; Liskamp,
R. M. J. Tetrahedron Lett. 2000, 41, 7991.
1H NMR (400 MHz, DMSO-d6): d = 7.70 (br s, NH3 ), 4.80 (br s, 1
+
(18) Brouwer, A. J.; Monnee, M. C. F.; Liskamp, R. M. J.
Synthesis 2000, 1579.
(19) Lowik, D. W. P. M.; Liskamp, R. M. J. Eur. J. Org. Chem.
2000, 1219.
H, OH), 3.83 (dd, J = 4.2, 11.2 Hz, 1 H, OCHH), 3.35 (dd, J = 2.4,
11.2 Hz, 1 H, OCHH), 3.14 (dd, J = 3.7, 13.0 Hz, 1 H, NCHH), 2.97
(dd, J = 9.2, 13.0 Hz, 1 H, NCHH), 2.76 (dddd, J = 2.4, 3.7, 4.2, 9.2
Hz, 1 H, CH).
(20) Cordero, F. M.; Cacciarini, M.; Machetti, F.; De Sarlo, F.
Eur. J. Org. Chem. 2002, 1407.
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16, 1500.
13C NMR (100 MHz, DMSO-d6): d = 59.2, 58.2, 38.1.
MS (Positive-ESI): m/z = 156 (MH)+.
HRMS (Negative-SIMS): m/z calcd for C3H9NO4S, 154.0174 [M –
H]–; found, 154.0180.
(23) Xu, J. X.; Xu, S. Synthesis 2004, 276.
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S. L. J. Org. Chem. 1980, 45, 4254.
(S)-1-Amino-3-hydroxypropane-2-sulfonic Acid [(S)-6d]
Yield: 77%; colorless crystals; mp 221–222 °C.
96% ee.
[a]D20 +26.4 (c 1.32, 88% HCO2H).
(27) Stewart, J. M. J. Org. Chem. 1963, 28, 596.
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Pharmacol. 1987, 36, 2109.
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57, 2471.
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1989, 54, 1295.
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Anthonsen, T. Tetrahedron: Asymmetry 1995, 6, 499.
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Polym. Sci., Part A: Polym. Chem. 2002, 40, 3443.
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F.; Isac-Garcia, J.; Santoyo-Gonzalez, F. J. Org. Chem.
1997, 62, 3944.
IR (KBr): 3396.4, 3087.6 (br, NH, OH), 1211.7 (SO2), 1165.5 (SO2)
cm–1.
+
1H NMR (400 MHz, DMSO-d6): d = 7.69 (br s, NH3 ), 4.80 (br s, 1
H, OH), 3.83 (dd, J = 4.2, 11.2 Hz, 1 H, OCHH), 3.35 (dd, J = 2.4,
11.2 Hz, 1 H, OCHH), 3.14 (dd, J = 3.7, 13.0 Hz, 1 H, NCHH), 2.97
(dd, J = 9.2, 13.0 Hz, 1 H, NCHH), 2.76 (dddd, J = 2.4, 3.7, 4.2, 9.2
Hz, 1 H, CH).
13C NMR (100 MHz, DMSO-d6): d = 59.2, 58.2, 38.1.
MS (ESI, positive ion): m/z = 156 (MH)+.
HRMS (Negative-SIMS): m/z calcd for C3H9NO4S, 154.0174 [M –
H]–; found, 154.0179.
Acknowledgment
The project was supported partly by the National Natural Science
Foundation of China (No. 20272002 and 20472005), Ministry of
Education of P. R. China (SRF for ROCS and EYTP), and Peking
University (President grant).
Synthesis 2005, No. 13, 2122–2128 © Thieme Stuttgart · New York