Versatile synthesis of free and N-benzyloxycarbonyl-protected 2,2-disubstituted taurines

Article abstract of DOI:10.1002/ejoc.200700791

An effective and versatile method was developed to synthesize N-benzyloxycarbonyl-protected and free 2,2-disubstituted taurines. Several novel 2,2-disubstituted taurines, including aliphatic/aromatic and cyclic/acyclic derivatives, were obtained, which demonstrates the generality of this method. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200700791

FULL PAPER
DOI: 10.1002/ejoc.200700791
Versatile Synthesis of Free and N-Benzyloxycarbonyl-Protected
2,2-Disubstituted Taurines
Boyuan Wang,[a] Wei Zhang,[a] Leilei Zhang,[b] Da-Ming Du,[a] Gang Liu,[b] and
Jiaxi Xu*[a,c]
Keywords: Amino acid / Aminoalkanesulfonic acid / Ketone / Synthesis / Taurine
An effective and versatile method was developed to synthe-
size N-benzyloxycarbonyl-protected and free 2,2-disubsti-
tuted taurines. Several novel 2,2-disubstituted taurines, in-
cluding aliphatic/aromatic and cyclic/acyclic derivatives,
were obtained, which demonstrates the generality of this
method.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
alkyl-substituted taurines from 2,2-disubstituted azirid-
ines,[14] the preparation of aryl 2,2-disubstituted taurines
proved futile, as such N-acetyl aryl taurines decomposed
when heated at reflux in aqueous hydrochloric acid in the
deacetylation step. Herein, we present a method of good
generality for the synthesis of various N-benzyloxycar-
bonyl-protected and free 2,2-disubstituted taurines from
ketones.
Introduction
Taurine and substituted taurines are not only very im-
portant sulfur analogues of naturally occurring aminocar-
boxylic acids, but they are also one class of important natu-
rally occurring amino acids. They have been found in many
mammalian tissues and are involved in various physiologi-
cal processes.[1,2] In contrast, their derivatives, especially sul-
fonopeptides, have been widely used as enzyme inhibitors
and haptens in the development of catalytic antibodies dur-
ing the last two decades because of their tetrahedral struc-
ture.[2–6]
Results and Discussion
Recently, α,α-disubstituted amino acids have been widely
As part of our ongoing program to synthesize structur-
used as building blocks to prepare peptidomimetics for pep- ally diverse substituted taurines, we prepared 1-monosubsti-
tide-like drug discovery with better biological stability.[7–10] tuted and 1,1- and 1,2-disubstituted taurines effectively
As sulfur analogues of naturally occurring amino acids, from simple starting materials, such as alkenes, epoxides,
some gem-disubstituted aminoalkanesulfonic acids,[11–13]
a
ketones;[11,15,16,18] 2-monosubstituted, and 1,2- and 2,2-di-
series of 1,1-disubstituted taurines,[11] and a few 2,2-disub- substituted taurines from various aziridines.[14,19]
stituted taurines[12,13] and vic-disubstituted taurines[14–17]
2-Amino-2-methylpropanesulfonic acid, the simplest 2,2-
have been synthesized to date. For the investigation of bio- disubstituted taurine, has been synthesized from 2-methyl-
logical activities and structure–activity relationships, the alanine,[12] acetone cyanohydrin,[12] and 2,2-dimethyl-β-sul-
discovery of peptidomimetic drug, and the synthesis of sul- tam.[13] We also prepared 2,2-dialkyl-substituted taurines
fonopeptides, we wish to develop efficient methods to pre- efficiently from 2,2-dialkyl-substituted aziridines. However,
pare structurally diverse substituted taurines. Although we when the method was extended to prepare aromatic 2,2-
recently reported an efficient method to synthesize 2,2-di- disubstituted taurines, monoaryl 2,2-disubstituted taurines
were obtained in very low yields and no 2,2-diaryl taurine
[a] Beijing National Laboratory for Molecular Sciences (BNLMS),
was afforded due to complex decomposition in the deacety-
College of Chemistry and Molecular Engineering, Peking
lation step. We therefore hoped to develop a general and
University,
Beijing 100871, P. R. China
versatile method for the synthesis of structurally diverse free
and N-benzyloxycarbonyl-protected 2,2-disubstituted taur-
ines from commercially available ketones.
At first, acetophenone (1a) was selected as a model to
prepare the 2,2-disubstituted taurine 2-amino-2-phenylpro-
panesulfonic acid as well as its N-benzyloxycarbonyl deriva-
tive. Cyanoamination of acetophenone afforded 2-amino-2-
phenylproponitrile (2a), which was hydrolyzed in hydro-
chloric acid to give 2-phenylalanine (3a).[20] To simplify the
Fax: +86-10-6275-1708
E-mail: jxxu@pku.edu.cn
[b] Institute of Materia Medica, Chinese Academy of Medical
Sciences,
Beijing 100050, P. R. China
[c] College of Science, Beijing University of Chemical Technology,
Beijing 100029, P. R. China
Fax: +86-10-6275-1708
E-mail: jxxu@mail.buct.edu.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
350
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 350–355

Synthesis of Free and N-Benzyloxycarbonyl-Protected Taurines
separation of the desired amino acid from the inorganic salt
ammonium chloride, 2-phenylanaline (3a) was protected
directly with benzyl chloroformate to yield N-benzyloxy-
carbonyl-2-phenylanaline (Z-3a), which was easily extracted
with ethyl acetate from the aqueous solution. This is a con-
venient method to separate amino acids from an aqueous
solution after the Strecker synthesis. However, the sodium
borohydride–iodine reduction of N-benzyloxycarbonyl-2-
phenylanaline (Z-3a) afforded 2-amino-2-phenylpropanol
(4a) instead of the corresponding 2-N-benzyloxycarbonyl-
amino-2-phenylpropanol (5a). The protecting group was re-
moved during the reduction. Similar results were also ob-
served in the reduction of 1-benzyloxycarbonylamino-1-cy-
clohexanecarboxylic acid (Z-3e), whereas the reduction of
Z-3e with sodium borohydride furnished benzyl N-cyclo-
hexylcarbamate. Decarboxylation occurred during the re-
duction.
Alternatively, 2-phenylanaline (3a) was first purified
through recrystallization from ethanol, then reduced with
sodium borohydride–iodine to afford 2-amino-2-phenyl-1-
propanol (4a),[21] which was directly treated with benzyl
chloroformate to give rise to N-protected amino alcohol 5a
in a good overall yield of 82%. Amino alcohol 4a was not
separated, as either distillation or silica gel chromatography
would impair the overall yields owing to its high boiling
point and strong polarity.
Scheme 1. Attempt to synthesize N-Z-protected 2,2-disubstituted
taurines.
Because sodium sulfite or bisulfite displacement of the
amino alcohol methanesulfonate is the most efficient
method to synthesize 2-substituted taurines,[22] we con-
verted N-protected amino alcohol 5a into its methanesul-
fonate (6a) with methanesulfonic chloride.[15] Unfortu-
nately, sodium sulfite/bisulfite displacement was unsuccess-
ful possibly due to the steric hindrance around the meth-
anesulfonate group. Furthermore, methanesulfonate 6a can-
not react with potassium thioacetate to prepare corre-
sponding amino alcohol thioacetate 7a (Scheme 1). Conse-
Scheme 2. General route for the synthesis of N-Z-protected and
free 2,2-disubstituted taurines.
quently, alcohol 5a was converted into thioacetate 7a by the drolysis of 5,5-diphenylhydantoin,[23] which was synthesized
Mitsunobu reaction with thiolacetic acid, DEAD (diethyl from benzil and urea.[24] After reduction with sodium
azodicarboxylate), and triphenylphosphane.[15]
borohydride–iodine and subsequent N-acylation with ben-
Finally, thioacetate 7a was oxidized in performic acid zyl chloroformate, N-benzyloxycarbonyl-protected 2,2-di-
to afford 2-(benzyloxycarbonyl)amino-2-phenylpropanesul- substituted vicinal amino alcohols 5 were obtained in good
fonic acid (8a) in good yield. After the oxidation was com- yields. Protected amino alcohols 5 were further converted
plete, formaldehyde was added into the reaction mixture to into corresponding thioacetates 7 in acceptable-to-satisfac-
eliminate the excess amount of oxidant, because aromatic tory yields by Mitsunobu reaction with thiolacetic acid. 2,2-
2,2-disubstituted taurines are unstable under the oxidizing Diphenyl glycinol (6f) gave corresponding thioacetate 7f in
conditions (Scheme 2).
a low yield of 17% because of more bulky steric hindrance
Free 2-amino-2-phenylpropanesulfonic acid (9a) was ob- around its hydroxy group. Thioacetates 7 were dissolved in
tained in excellent yield by hydrogenolysis in methanol un- formic acid and oxidized with performic acid to afford N-
der an atmosphere of hydrogen in the presence of palladium benzyloxycarbonyl protected 2,2-disubstituted taurines
on carbon powder (Scheme 2).[15] The time of hydro- 8.[14,15] N-Benzyloxycarbonyl-2,2-diphenyltaurine (8f) is
genolysis should be carefully controlled to avoid further N- quite unstable in performic acid and partly decomposes to
benzylic cleavage.
2,2-diphenyltaurine (9f). Free 2,2-disubstituted taurines 9
After successful synthesis of 2-amino-2-phenylpro- were obtained in good-to-excellent yields after palladium-
panesulfonic acid (8a) and its N-benzyloxycarbonyl deriva- catalyzed hydrogenolysis in methanol (Scheme 2). For N-
tive 9a from acetophenone, a series of commercially avail- protected 2,2-diphenyltaurine (8f), the corresponding de-
able ketones 1 were converted into α,α-disubstituted α- sired free 2,2-diphenyl taurine was also obtained in high
amino acids 3 by Strecker amino acid synthesis. 2,2-Di- yield through careful time control: prolonged hydro-
phenylglycine (3f) was prepared from sodium hydroxide hy- genolysis could result in N-benzylic cleavage, which would
Eur. J. Org. Chem. 2008, 350–355
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
351

B. Wang, W. Zhang, L. Zhang, D.-M. Du, G. Liu, J. Xu
FULL PAPER
ice–water bath) was poured into the flask through the top of the
condenser. The resulting mixture was stirred overnight, diluted with
water (150 mL), and heated at reflux for 3 h. The azeotrope of re-
maining ketone 1, HCl, and water was distilled off. The aqueous
phase was extracted with CH2Cl2 (20 mL). The aqueous solution
was evaporated under vacuum to give a colorless-to-brown residue,
which was dissolved in warm water (50 mL) and then neutralized
by sodium hydroxide to reach pH 3–4. To the solution was added
ethanol (or a mixture of ethanol and ether) as quickly as possible.
After standing overnight, the white solid that precipitated from the
solution was collected with a Buchner funnel. The solid was puri-
fied by recrystallization from a mixture of ethanol and water (or
ether) to give pure colorless crystals 3.
give rise to 2,2-diphenylethanesulfonic acid (10f) as a by-
product; this was confirmed by an authentic sample synthe-
sized from 2,2-diphenylethyl thioacetate (11) by performic
acid oxidation.[25] In this way, a series of N-benzyloxycar-
bonyl protected and free 2,2-disubstituted taurines, includ-
ing aliphatic/aromatic and cyclic/acyclic derivatives, were ef-
ficiently synthesized.
Conclusions
Aliphatic and aromatic, cyclic and acyclic, and free and
N-benzyloxycarbonyl-protected 2,2-disubstituted taurines
were synthesized from ketones by Strecker amino acid syn-
thesis, reduction with sodium borohydride–iodine, protec-
tion with benzyl chloroformate, Mitsunobu thioacetylation
with thiolacetic acid, oxidation with performic acid, and
subsequent hydrogenolysis in the presence of palladium on
carbon powder. This route could serve as a general ap-
proach to structurally diverse 2,2-disubstituted taurines.
General Procedure for the Preparation of N-Benzyloxycarbonyl Pro-
tected Amino Alcohols 5: To a 100-mL round-bottomed flask
charged with amino acid 3 (10 mmol), NaBH4 (0.95 g, 25 mmol),
and anhydrous THF (30 mL) was added dropwise a solution of
iodine (2.54 g, 10 mmol) in anhydrous THF (7 mL) through a pres-
sure-equalizing addition funnel equipped with a CaCl2 desiccating
tube whilst keeping the temperature at 0 °C. When the addition
was complete and the evolution of hydrogen gas ceased, the mix-
ture was stirred and heated at reflux for 20 h and then cooled to
room temperature. The reaction was cautiously quenched with
methanol to produce a clear solution. The mixture was stirred for
30 min, and the solution was concentrated under vacuum to give a
white paste, which was then dissolved in 20% aqueous KOH and
stirred overnight. The mixture was diluted with water and extracted
with CH2Cl2 (3ϫ15 mL). The combined organic phase was dried
with Na2SO4, and the solvent was removed thoroughly under vac-
uum to give an oily or crystalline product amino alcohol 4, which
was used directly in the next step. A 100-mL three-necked round-
bottomed flask containing amino alcohol 4 (about 10 mmol) in
CH2Cl2 (50 mL) was equipped with a magnetic stirring bar and
two pressure-equalizing addition funnels containing aqueous
NaOH (0.39 g, 9.8 mmol in 20 mL water) and a solution of 50 wt.-
% CbzCl in toluene (3.41 g, 10 mmol, diluted with 10 mL of
CH2Cl2), respectively. In a –10 °C ice–salt bath, the aqueous NaOH
and CbzCl solutions were added dropwise simultaneously over 1 h.
The reaction mixture was stirred vigorously throughout the ad-
dition. After the addition, the ice–salt bath was warmed to room
temperature and vigorous stirring was continued for 15 h. The or-
ganic layer was separated, and the aqueous layer was extracted with
CH2Cl2 (2ϫ10 mL). The combined organic phase was dried with
anhydrous MgSO4, concentrated under vacuum, and purified by
recrystallization or silica gel column chromatography to afford N-
benzyloxycarbonylamino alcohol 6 as colorless crystals or oil.
Experimental Section
General Remarks: Melting points were measured with a Yanaco
MP-500 melting point apparatus, which was calibrated with eight
standard samples with melting points in the range from 50 to
250 °C. 1H NMR and 13C NMR spectra were recorded with a Var-
ian Mercury 200 (200 MHz) or Varian Mercury Plus 300
(300 MHz) spectrometer in CDCl3 with TMS as an internal stan-
dard, in D2O, or in [D6]DMSO. Mass spectra were obtained with
a Bruker ESQUIRE~LC ESI ion trap mass spectrometer. HRMS
data was obtained with an Agilent LC/MSD TOF mass spectrome-
ter. IR spectra were determined with a Nicolet AVATAR 330 FTIR
spectrometer. C, H, and N analyses were recorded with an Ele-
mentar Vario EL analyzer. Amino nitriles 2a–e were prepared from
ketones 1a–e in acceptable-to-good yields according to a literature
method.[26] Amino acids 3a–e were prepared from amino nitriles
2a–e in acceptable-to-good yields according to a modified literature
method.[20] Amino acid 3f was prepared from 5,5-diphenylhydan-
toin,[23] which was obtained from benzil and urea in good yield.[24]
The analytical data of all known compounds are identical to those
reported in the literature.
General Procedure for the Preparation of Amino Acids 3: Amino
acids 3a–e were prepared from amino nitriles 2a–e by a modified
literature method.[20] A 250-mL round-bottomed flask equipped
with a magnetic stirring bar was charged with ketone 1 (150 mmol),
NH4Cl (9.20 g, 172 mmol), ammonia (20 mL, 270 mmol), ethanol
(45 mL), and water (38 mL). After the mixture was dissolved into
a clear solution, NaCN (8.50 g, 173 mmol) was added, and the
flask was quickly sealed with a rubber stopper. The mixture was
stirred for 3 d (for 2a and 2b, the mixture was heated cautiously to
65 °C and stirred for 8 h; for 2c, 1.0 g of benzyltriethylammonium
chloride was added), which resulted in a colorless-to-dark-brown
solution, which was cooled to room temperature, and extracted
with CH2Cl2 (3ϫ30 mL). The combined organic layer was washed
with water to remove the remaining NaCN, dried with anhydrous
sodium sulfate, and concentrated under reduced pressure to afford
a residue amino nitrile 2, which was used directly in the next step
without purification. The flask containing amino nitrile 2 was
equipped with a magnetic stirring bar and a condenser, and cooled
in an ice–water bath. Hydrochloric acid (150 mL, precooled in an
Benzyl N-(2-Hydroxy-1-methyl-1-phenyl)ethylcarbamate (5a): Col-
orless crystals, m.p. 57–58.5 °C, overall yield 82% from amino acid
3a. Rf = 0.23 [petroleum ether (60–90 °C)/ethyl acetate, 3:1; silica
1
gel plate]. H NMR (300 MHz, CDCl3): δ = 7.40–7.15 (m, 10 H,
ArH), 5.81 (br. s, 1 H, NH), 5.00 (s, 2 H, CH2O), 3.66 (d, J =
10.8 Hz, 1 H in CH2), 3.59 (s, 1 H, OH), 3.47 (d, J = 10.8 Hz, 1 H
in CH2), 1.57 (s, 3 H, CH3) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 155.7, 142.9, 136.2, 128.3, 127.9, 126.9, 125.3, 70.5, 66.4, 59.5,
23.1 ppm. IR: ν = 3292.0 (br., NH & OH), 1701.2 (C=O) cm–1.
˜
MS (ESI): m/z = 308 [M + Na]+. C17H19NO3 (285.34): calcd. C
71.56, H 6.71, N 4.91; found C 71.46, H 6.93, N 4.86.
Benzyl N-(1-Hydroxymethyl-1-phenyl)propylcarbamate (5b): Color-
less crystals, m.p. 87.5–88.5 °C, overall yield 93% from amino acid
3b. Rf = 0.24 [petroleum ether (60–90 °C)/ethyl acetate, 3:1; silica
1
gel plate]. H NMR (200 MHz, CDCl3): δ = 7.40–7.21 (m, 10 H,
ArH), 5.52 (s, 1 H, NH), 5.06 (s, 2 H, CH2O), 3.98 (d, J = 11.4 Hz,
352
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 350–355

Synthesis of Free and N-Benzyloxycarbonyl-Protected Taurines
1 H in OCH2), 3.84 (d, J = 11.4 Hz, 1 H in OCH2), 3.70 (br. s, 1 ppm. 13C NMR (75.5 MHz, CDCl3): δ = 154.4, 141.4, 136.1, 128.4,
H, OH), 1.96 (m, CH2), 0.76 (d, J = 7.2 Hz, 3 H, CH3) ppm. 13C 128.2, 127.7, 127.4, 124.9, 72.9, 66.1, 57.2, 36.3, 24.1 ppm. IR: ν =
˜
NMR (50.3 MHz, CDCl3): δ = 156.2, 141.9, 136.2, 128.5, 128.4, 3399.8 (NH), 1724.4 (C=O), 1264.5 (SO2), 1179.7 (SO2) cm–1. MS
128.1, 127.0, 125.9, 68.3, 66.7, 63.2, 29.8, 7.7 ppm. IR: ν = 3264.4 (ESI): m/z = 386 [M + Na]+. C18H21NO5S (363.43): calcd. C 59.49,
˜
(br., NH & OH), 1688.9 (C=O) cm–1. MS (ESI): m/z = 322 [M +
Na]+. C18H21NO3 (299.36): calcd. C 72.22, H 7.07, N 4.68; found
C 71.96, H 7.12, N 4.51.
H 5.82, N 3.85; found C 59.50, H 5.78, N 3.80.
General Procedure for Synthesis of 2-Substituted-2-(Benzyloxycar-
bonyl)aminoalkyl Thioacetates 7: To an efficiently stirred solution
of triphenylphosphane (2.62 g, 10 mmol) in anhydrous THF
(12 mL) was added dropwise a solution of diethyl azodicarboxylate
(DEAD, 1.74 g, 10 mmol) in anhydrous THF (6 mL) at –10 °C over
15 min. The resulting mixture was stirred at –10 °C for another
0.5 h. A white precipitate appeared. A solution of Cbz-amino
alcohol 5 (5 mmol) and thiolacetic acid (0.76 g, 10 mmol) in anhy-
drous THF (12 mL) was added dropwise over 30 min, and the reac-
tion mixture was stirred for an additional 2 h at –10 °C to give a
clear-orange solution. Further stirring at room temperature turned
the solution from orange to yellow, indicating the reaction was
complete. After concentrated under reduced pressure, tri-
phenylphosphane oxide was crystallized upon the addition of a
mixture of ethyl acetate and petroleum ether (60–90 °C). After fil-
tration, the combined filtrates were concentrated in vacuo and sub-
jected to silica gel column chromatography [petroleum ether (60–
90 °C)/ethyl acetate, 8:1] to afford colorless thioacetate 7. For
alcohol 6f, triphenylphosphane (3.28 g, 12.5 mmol), diethyl azo-
dicarboxylate (2.18 g, 12.5 mmol), and thiolacetic acid (0.95 g,
12.5 mmol) were added.
Benzyl N-(1-Benzyl-2-hydroxy-1-methyl)ethylcarbamate (5c): Col-
orless crystals, m.p. 77–78 °C, overall yield 98% from amino acid
3c. Rf = 0.23 [petroleum ether (60–90 °C)/ethyl acetate, 3:1; silica
gel plate]. 1H NMR (200 MHz, CDCl3): δ = 7.40–7.30 (m, 5 H,
ArH), 7.30–7.20 (m, 3 H, ArH), 7.19–7.09 (m, 2 H, ArH), 5.14 (d,
J = 12 Hz, 1 H in CH2O), 5.05 (d, J = 12 Hz, 1 H in CH2O), 4.84
(br. s, 1 H, NH), 3.68 (s, 2 H, CH2), 3.58 (br. s, 1 H, OH), 3.11 (d,
J = 13.6 Hz, 1 H in CH2), 2.82 (d, J = 13.6 Hz, 1 H in CH2), 1.11
(s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 156.2, 136.7,
136.4, 130.6, 128.6, 128.2, 126.6, 68.8, 66.6, 57.3, 41.1, 22.6 ppm.
IR: ν = 3228.2 (br., NH & OH), 1667.5 (C=O) cm–1. MS (ESI):
˜
m/z = 322 [M + Na]+. C18H21NO3 (299.36): calcd. C 72.22, H 7.07,
N 4.68; found C 72.26, H 7.07, N 4.60.
Benzyl N-(2-Hydroxy-1,1-dimethyl)ethylcarbamate (5d):[27] Color-
less oil, overall yield 86% from amino acid 3d. Rf = 0.25 [petroleum
ether (60–90 °C)/ethyl acetate, 3:1; silica gel plate]. 1H NMR
(300 MHz, CDCl3): δ = 7.37–7.30 (m, 5 H, ArH), 5.14 (br. s, 1 H,
NH), 5.04 (s, 2 H, CH2O), 3.73 (br. s, 1 H, OH), 3.56 (s, 2 H, CH2),
1.26 (s, 6 H, 2 CH3) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 156.0,
136.2, 128.4, 128.02, 127.96, 70.0, 66.4, 54.3, 24.2 ppm.
2-(Benzyloxycarbonyl)amino-2-phenylpropyl Thioacetate (7a): Col-
orless crystals, m.p. 66–68 °C, yield 67%. Rf = 0.32 [petroleum
ether (60–90 °C)/ethyl acetate, 6:1; silica gel plate]. 1H NMR
(200 MHz, CDCl3): δ = 7.44–7.22 (m, 10 H, ArH), 5.56 (s, 1 H,
NH), 5.03 (s, 2 H, CH2O), 3.58 (d, J = 14.0 Hz, 1 H in CH2), 3.40
(d, J = 14.0 Hz, 1 H in CH2), 2.34 (s, 3 H, CH3), 1.72 (s, 3 H, CH3)
ppm. 13C NMR (50.3 MHz, CDCl3): δ = 196.2, 154.7, 144.4, 136.5,
128.5, 128.4, 128.0, 127.2, 125.1, 66.2, 58.2, 40.4, 30.3, 25.6 ppm.
Benzyl N-[(1-Hydroxymethyl)cyclohexyl]carbamate (5e): Colorless
crystals, m.p. 90–90.5 °C, overall yield 90% from amino acid 3e. Rf
= 0.22 [petroleum ether (60–90 °C)/ethyl acetate, 3:1; silica gel
plate]. 1H NMR (300 MHz, CDCl3): δ = 7.40–7.29 (m, 5 H, ArH),
5.06 (s, 2 H, CH2O), 4.89 (br. s, 1 H, NH), 3.79 (br. s, 1 H, OH),
3.67 (s, 2 H, CH2), 1.82 (m, 2 H in 2 CH2), 1.55–1.30 (m, 2 H in 2
CH2 & 6 H in 3 CH2) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
156.1, 136.2, 128.5, 128.1, 128.0, 69.1, 66.6, 56.4, 31.9, 25.5,
IR: ν = 3330.0 (NH), 1686.3 (C=O) cm–1. MS (ESI): m/z = 366 [M
˜
21.3 ppm. IR: ν = 3456.8 (NH), 3285.9 (OH), 1703.4 (C=O) cm–1.
˜
+ Na]+. C19H21NO3S (343.44): calcd. C 66.45, H 6.16, N 4.08;
found C 66.16, H 6.20, N 4.02.
MS (ESI): m/z = 286 [M + Na]+. C15H21NO3 (263.33): calcd. C
68.42, H 8.04, N 5.32; found C 68.43, H 7.86, N 5.24.
2-(Benzyloxycarbonyl)amino-2-phenylbutyl Thioacetate (7b): Color-
less crystals, m.p. 53.5–55 °C, yield 60%. Rf = 0.31 [petroleum ether
(60–90 °C)/ethyl acetate, 6:1; silica gel plate]. H NMR (200 MHz,
CDCl3): δ = 7.45–7.20 (m, 10 H, ArH), 5.24 (s, 1 H, NH), 5.06 (s,
2 H, CH2O), 3.88 (d, J = 13.4 Hz, 1 H in CH2), 3.72 (d, J =
13.4 Hz, 1 H in CH2), 2.31 (s, 3 H, CH3), 2.02 (m, 2 H, CH2), 0.71
(t, J = 7.7 Hz, 3 H, CH3) ppm. 13C NMR (75.5 MHz, CDCl3): δ
= 195.4, 155.6, 142.4, 136.5, 128.5, 128.3, 128.1, 127.1, 125.6, 66.5,
Benzyl N-(2-Hydroxy-1,1-diphenyl)ethylcarbamate (5f): Colorless
crystals, m.p. 133–135 °C, overall yield 72% from amino acid 3f. Rf
= 0.34 [petroleum ether (60–90 °C)/ethyl acetate, 3:1; silica gel
plate]. 1H NMR (200 MHz, CDCl3): δ = 7.50–7.21 (m, 15 H, ArH),
5.84 (s, 1 H, NH), 5.09 (s, 2 H, CH2O), 4.38 (s, 2 H, CH2), 4.29
(br. s, 1 H, OH) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 156.5,
142.0, 135.9; 128.53, 128.47, 128.3, 128.2, 127.7, 127.3, 69.8, 67.2,
1
66.6 ppm. IR: ν = 3216.6 (br., NH & OH), 1687.9 (C=O) cm–1.
˜
61.4, 37.0, 31.8, 30.5, 24.9, 7.9 ppm. IR: ν = 3333.7 (NH), 1707.1
˜
MS (ESI): m/z = 370 [M + Na]+. C22H21NO3 (347.41): calcd. C
(C=O), 1692.1 (C=O) cm–1. MS (ESI): m/z = 380 [M + Na]+.
C20H23NO3S (357.47): calcd. C 67.20, H 6.49, N 3.92; found C
66.88, H 6.40, N 3.86.
76.06, H 6.09, N 4.03; found C 75.78, H 6.04, N 4.22.
2-(Benzyloxycarbonyl)amino-2-phenylpropyl Methanesulfonate (6a):
To an ice-cooled solution of 5a (0.790 g, 2.77 mmol) and triethyl-
amine (0.312 g, 3.1 mmol) in dichloromethane (15 mL) was added
a solution of MsCl (0.382 g, 3.33 mmol) in CH2Cl2 (10 mL) drop-
wise over 0.5 h. The mixture was evaporated in vacuo, and the resi-
due was treated with EtOAc and H2O. The separated organic layer
was washed with 5% aqueous NaHCO3 and brine and dried with
Na2SO4. After removal of the solvent, the residue was recrystallized
from petroleum ether (60–90 °C)/ethyl acetate to give colorless
crystals of 6a in 91% yield. M.p. 106.5–107.5 °C. Rf = 0.27 [petro-
2-(Benzyloxycarbonyl)amino-2-methyl-3-phenylpropyl Thioacetate
(7c): Colorless crystals, m.p. 42.5–43.5 °C, yield 45%. Rf = 0.40
[petroleum ether (60–90 °C)/ethyl acetate, 6:1; silica gel plate]. 1H
NMR (200 MHz, CDCl3): δ = 7.39–7.32 (m, 5 H, ArH), 7.28–7.20
(m, 3 H, ArH), 7.09–7.02 (m, 2 H, ArH), 5.14 (d, J = 12.5 Hz, 1
H in CH2O), 5.04 (d, J = 12.5 Hz, 1 H in CH2O), 4.74 (s, 1 H,
NH), 3.51 (d, J = 13.8 Hz, 1 H in CH2), 3.27 (d, J = 13.4 Hz, 1 H
in CH2), 3.23 (d, J = 13.8 Hz, 1 H in CH2), 2.83 (d, J = 13.4 Hz,
1 H in CH2), 2.33 (s, 3 H, CH3), 1.16 (s, 3 H, CH3) ppm. 13C NMR
(50.3 MHz, CDCl3): δ = 195.6, 154.7, 136.64, 136.57, 130.5, 128.5,
1
leum ether (60–90 °C)/ethyl acetate, 3:1; silica gel plate]. H NMR
(300 MHz, CDCl3): δ = 7.50–7.23 (m, 10 H, ArH), 5.54 (s, 1 H,
NH), 5.03 (s, 2 H, CH2O), 4.64 (d, J = 9.0 Hz, 1 H in CH2), 4.43 128.2, 128.11, 128.07, 126.6, 66.1, 55.9, 43.1, 37.7, 30.4, 23.5 ppm.
(d, J = 9.0 Hz, 1 H in CH2), 2.72 (s, 3 H, CH3), 1.68 (s, 3 H, CH3) IR: ν = 3351.9 (NH), 1717 (C=O), 1692.0 (C=O) cm–1. MS (ESI):
˜
Eur. J. Org. Chem. 2008, 350–355
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
353

B. Wang, W. Zhang, L. Zhang, D.-M. Du, G. Liu, J. Xu
FULL PAPER
m/z = 380 [M + Na]+. C20H23NO3S (357.47): calcd. C 67.20, H
CH2), 1.98 (m, 1 H in CH2), 0.76 (br. s, 3 H, CH3) ppm. 13C NMR
6.49, N 3.92; found C 67.08, H 6.48, N 3.82.
(50.3 MHz, [D6]DMSO): δ = 154.4, 145.4, 137.6, 130.8, 128.4,
127.8, 127.5, 125.9, 125.8, 64.8, 59.2, 56.7, 31.3, 8.7 ppm. IR: ν =
˜
2-(Benzyloxycarbonyl)amino-2-methylpropyl Thioacetate (7d): Light
yellowish oil, yield 57%. Rf = 0.40 [petroleum ether (60–90 °C)/
ethyl acetate, 6:1; silica gel plate]. H NMR (200 MHz, CDCl3): δ
3351.5 (br., NH & OH), 1680.1 (C=O), 1248.5 (SO2), 1170.2 (SO2)
cm–1. MS (ESI): m/z = 362 [M – H]–. HRMS: calcd. for
C18H21NNaO5S 386.1032; found 386.1036.
1
= 7.34 (m, 5 H, ArH), 5.05 (s, 2 H, CH2O), 4.93 (br. s, 1 H, NH),
3.30 (s, 2 H, CH2), 2.34 (s, 3 H, CH3), 1.34 (s, 6 H, 2 CH3) ppm. 2-(Benzyloxycarbonyl)amino-2-methyl-3-phenylpropanesulfonic Acid
13C NMR (50.3 MHz, CDCl3): δ = 195.6, 154.6, 136.5, 128.41, (8c): Colorless crystals, m.p. 102–105 °C (dec.), yield 88%. Rf =
128.40, 128.0, 66.1, 53.0, 38.7, 30.5, 26.3 ppm. IR: ν = 3353.8
0.41 (chloroform/methanol, 4:1; silica gel plate). 1H NMR
(200 MHz, [D6]DMSO): δ = 7.59 (br. s, 1 H, NH), 7.37 (s, 5 H,
ArH), 7.21–7.06 (m, 5 H, ArH), 5.09 (d, J = 12.4 Hz, 1 H in
CH2O), 4.96 (d, J = 12.4 Hz, 1 H in CH2O), 3.47 (d, J = 13.0 Hz,
1 H in CH2), 2.80 (d, J = 13.0 Hz, 1 H in CH2), 2.54 (s, 2 H, CH2),
1.43 (s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, [D6]DMSO): δ =
154.5, 137.9, 137.6, 130.83, 130.80, 128.5, 127.9, 126.2, 64.7, 56.7,
˜
(NH), 1695.0 (C=O) cm–1. MS (ESI): m/z = 304 [M + Na]+.
HRMS: calcd. for C14H19NNaO3S 304.0977; found 304.0981.
[1-(Benzyloxycarbonyl)aminocyclohexyl]methyl Thioacetate (7e):
Light yellowish oil (used directly with a little impurity), yield 68%.
Rf = 0.45 [petroleum ether (60–90 °C)/ethyl acetate, 6:1; silica gel
1
plate]. H NMR (300 MHz, CDCl3): δ = 7.36 (s, 5 H, ArH), 5.07
42.4, 53.8, 23.8 ppm. IR: ν = 3357.8 (br., NH & OH), 1283.3 (SO ),
˜
2
(s, 2 H, CH2O), 4.63 (s, 1 H, NH), 3.41 (s, 2 H, CH2), 2.33 (s, 3 H,
CH3), 1.98 (m, 2 H in 2 CH2), 1.55 (m, 2 H in 2 CH2), 1.47–1.40
(m, 4 H, 2 CH2), 1.26 (m, 2 H, CH2) ppm. MS (ESI): m/z = 344
[M + Na]+. HRMS: calcd. for C17H23NNaO3S 344.1296; found
344.1294.
1180.8 (SO2) cm–1. MS (ESI): m/z = 364 [M + H]+. HRMS: calcd.
for C18H22NO5S [M + H] 364.1213; found 364.1219.
2-(Benzyloxycarbonyl)amino-2-methylpropanesulfonic Acid (8d):
Colorless crystals, m.p. 98.5–100.5 °C (dec.), yield 84%. Rf = 0.37
(chloroform/methanol, 4:1; silica gel plate). 1H NMR (200 MHz,
[D6]DMSO): δ = 7.60 (br. s, 1 H, NH), 7.33 (s, 5 H, ArH), 4.94 (s,
2 H, CH2O), 2.68 (s, 2 H, CH2), 1.37 (s, 6 H, 2 CH3) ppm. 13C
NMR (50.3 MHz, [D6]DMSO): δ = 154.6, 137.5, 128.6, 128.0, 64.8,
2-(Benzyloxycarbonyl)amino-2,2-diphenylethyl Thioacetate (7f):
Colorless crystals, m.p. 106–107 °C, yield 17%. Rf = 0.38 [petro-
1
leum ether (60–90 °C)/ethyl acetate, 6:1; silica gel plate]. H NMR
(300 MHz, CDCl3): δ = 7.42–7.18 (m, 15 H, ArH), 5.90 (s, 1 H,
NH), 5.02 (s, 2 H, CH2O), 4.19 (s, 2 H, CH2), 2.23 (s, 3 H, CH3)
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 195.0, 154.9, 143.3, 136.4,
60.5, 51.1, 26.3 ppm. IR: ν = 3338.6 (br., NH & OH), 1688.5
˜
(C=O), 1215.5 (SO2), 1119.7 (SO2) cm–1. MS (ESI): m/z = 310 [M
+ Na]+. HRMS: calcd. for C12H17NNaO5S 310.0719; found
310.0720.
128.4, 128.3, 128.1, 127.4, 126.7, 66.7, 64.2, 39.0, 30.4 ppm. IR: ν
˜
= 3313.6 (NH), 1692.5 (C=O) cm–1. MS (ESI): m/z = 428 [M +
Na]+. C24H23NO3S (405.51): calcd. C 71.09, H 5.72, N 3.45; found
C 70.81, H 5.72, N 3.36.
[1-(Benzyloxycarbonyl)aminocyclohexyl]methanesulfonic Acid (8e):
Colorless crystals, m.p. 135–138 °C (dec.), yield 79%. Rf = 0.41
(chloroform/methanol, 4:1; silica gel plate). 1H NMR (300 MHz,
[D6]DMSO): δ = 7.30 (s, 5 H, Ph), 7.21 (br. s, 1 H, NH), 4.94 (s, 2
H, CH2O), 2.81 (s, 2 H, CH2), 2.16 (m, 2 H in 2 CH2), 1.72 (m, 2
H in 2 CH2), 1.50–1.20 (m, 6 H, 3CH2) ppm. 13C NMR (75.5 MHz,
[D6]DMSO): δ = 154.3, 137.5, 128.3, 127.62, 127.58, 64.5, 55.9,
General Procedure for the Preparation of N-Benzyloxycarbonyl-2,2-
disubstituted Taurines 8: To a performic acid solution, prepared by
mixing and stirring 30% H2O2 (1.2 mL) and 88% HCO2H (12 mL)
at room temperature for 1 h and cooled in an ice bath, was added
thioacetate 7 (2 mmol) in 88% HCO2H (2.7 mL) dropwise, keeping
the temperature at 0 °C. The reaction was stirred at 0 °C for an
additional 2 h and then quenched by the addition of 36% formal-
dehyde (10 mL). The resulting solution, along with the ice bath,
was warmed to room temperature over 2 h. Stirring was continued
until performic acid was removed completely (tested with KI–
starch paper). Then, the solution was poured into a Petri dish con-
taining silica gel. The mixture was air dried at room temperature
for 24–48 h. The residue was separated on a silica gel column (chlo-
roform/methanol, 8:1) to afford colorless crystals of 8. For
thioacetate 7f, silica gel column chromatography separation af-
forded N-Cbz taurine 8f in 66% yield and taurine 9f in 31% yield.
53.7, 32.6, 25.1, 21.9 ppm. IR: ν = 3335.2 (br., NH & OH), 1688.2
˜
(C=O), 1210.9 (SO2), 1177.3 (SO2) cm–1. MS (ESI): m/z = 350 [M
+ Na]+. HRMS: calcd. for C15H21NNaO5S 350.1019; found
350.1019.
2-(Benzyloxycarbonyl)amino-2,2-diphenylethanesulfonic Acid (8f):
Colorless crystals, m.p. 82.5–85 °C (dec.), yield 66%. Rf = 0.45
(chloroform/methanol, 4:1; silica gel plate). 1H NMR (300 MHz,
[D6]DMSO): δ = 8.65 (br. s, 1 H, NH), 7.36–7.18 (m, 15 H, ArH),
4.92 (s, 2 H, CH2O), 3.47 (s, 2 H, CH2) ppm. 13C NMR (75.5 MHz,
D2O): δ = 154.5, 143.1, 137.3, 128.40, 128.37, 127.7, 127.6, 127.3,
126.3, 65.0, 62.9, 60.9 ppm. IR: ν = 3363.5 (br., NH & OH), 1684.4
˜
(C=O), 1217.8 (SO2), 1176.5 (SO2) cm–1. MS (ESI): m/z = 434 [M
+ Na]+. HRMS: calcd. for C22H21NNaO5S 434.1032; found
434.1038.
2-(Benzyloxycarbonyl)amino-2-phenylpropanesulfonic Acid (8a):
Colorless crystals, m.p. 114–115.5 °C (dec.), yield 85%. Rf = 0.38
(chloroform/methanol, 4:1; silica gel plate). 1H NMR (300 MHz,
[D6]DMSO): δ = 8.30 (br. s, 1 H, NH), 7.40–7.13 (m, 10 H, ArH),
General Procedure for the Synthesis of 2,2-Disubstituted Taurines 9
4.92 (s, 2 H, CH2O), 2.68 (s, 2 H, CH2), 1.86 (s, 3 H, CH3) ppm. (Hydrogenolysis): Taurine 8 (0.50 mmol) was dissolved in methanol
13C NMR (75.5 MHz, [D6]DMSO): δ = 154.1, 147.0, 137.3, 128.4,
(5 mL), and 10% Pd on carbon powder (20 mg) was added. The
suspension was stirred under an atmosphere of hydrogen at room
temperature overnight (1 h for 8f). Methanol (20 mL) was added
to dissolve the precipitated product. The catalyst was removed by
hot filtration and was washed with methanol (2ϫ5 mL). Evapora-
tion of the solvent afforded taurine 9 as colorless crystals.
128.0, 127.8, 127.6, 126.0, 125.0, 64.8, 62.3, 56.0, 22.8 ppm. IR: ν
˜
= 3294.3 (br., NH & OH), 1694.5 (C=O), 1224.6 (SO2), 1181.5
(SO2) cm–1. MS (ESI): m/z = 348 [M – H]–. HRMS: calcd. for
C17H19NNaO5S 372.0876; found 372.0875.
2-(Benzyloxycarbonyl)amino-2-phenylbutanesulfonic Acid (8b): Col-
orless crystals, m.p. 130.5–132 °C (dec.), yield 93%. Rf = 0.38 (chlo-
2-Amino-2-phenylpropanesulfonic Acid (9a): Colorless crystals, m.p.
236–238 °C, yield 98%. Rf = 0.20 (chloroform/methanol, 4:1; silica
gel plate). 1H NMR (200 MHz, D2O): δ = 7.33–7.11 (m, 5 H, ArH),
3.26 (d, J = 14.4 Hz, 1 H in CH2), 3.15 (d, J = 14.4 Hz, 1 H in
1
roform/methanol, 4:1; silica gel plate). H NMR (200 MHz, [D6]-
DMSO): δ = 7.88 (br. s, 1 H, NH), 7.33 (s, 5 H, Ph), 7.25 (s, 5 H,
Ph), 4.96 (s, 2 H, CH2O), 3.11 (s, 2 H, CH2), 2.37 (m, 1 H in
354
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 350–355

Synthesis of Free and N-Benzyloxycarbonyl-Protected Taurines
CH2), 1.38 (s, 3 H, CH3) ppm. 13C NMR (50.3 MHz, D2O, DMSO
as internal standard): δ = 147.4, 130.4, 128.9, 127.1, 64.4, 55.7,
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of compounds 5, 6a, 7–9, 10f, and
31.1 ppm. IR: ν = 3373.4 (br., NH & OH), 1246.1 (SO ), 1196.4
11.
˜
2
(SO2) cm–1. MS (ESI): m/z = 216 [M + H]+. HRMS: calcd. for
C9H14NO3S [M + H] 216.0688; found 216.0691.
Acknowledgments
2-Amino-2-phenylbutanesulfonic Acid (9b): Colorless crystals, m.p.
253–255 °C, yield 99%. Rf = 0.26 (chloroform/methanol, 4:1; silica
gel plate). 1H NMR (300 MHz, D2O): δ = 7.42–7.20 (m, 5 H, ArH),
3.57 (d, J = 15.6 Hz, 1 H in CH2), 3.50 (d, J = 15.6 Hz, 1 H in
CH2), 2.26–2.02 (m, 2 H, CH2), 0.67 (t, J = 7.2 Hz, 3 H, CH3)
ppm. 13C NMR (75.5 MHz, D2O, DMSO as internal standard): δ
The project was supported partly by the National Natural Science
Foundation of China (No. 20472005) and Peking University (Presi-
dent grant).
= 139.0, 131.5, 131.0, 127.5, 63.3, 59.3, 34.3, 9.1 ppm. IR: ν =
˜
3425.0 (br., NH & OH), 1169.8 (SO2) cm–1. MS (ESI): m/z = 230
[M + H]+. HRMS: calcd. for C10H16NO3S [M + H] 230.0845;
found 230.0848.
[1]
For a review, see: R. J. Huxtable, Physiol. Rev. 1992, 72, 101–
163.
[2]
[3]
For a review, see: J. X. Xu, Chin. J. Org. Chem. 2003, 23, 1–9.
2-Amino-2-benzylpropanesulfonic Acid (9c): Colorless crystals, m.p.
197–199 °C, yield 90%. Rf = 0.22 (chloroform/methanol, 4:1; silica
gel plate). 1H NMR (200 MHz, D2O): δ = 7.30–7.05 (m, 5 H, ArH),
K. G. Carson, C. F. Schwender, H. N. Shroff, N. A. Cochran,
D. L. Gallant, M. J. Briskin, Bioorg. Med. Chem. Lett. 1997, 7,
711–714.
C. Gennari, C. Longari, S. Ressel, B. Salom, U. Piarulli, S.
Ceccarelli, A. Mielgo, Eur. J. Org. Chem. 1998, 2437–2449.
D. B. A. de Bont, K. M. Sliedregt-Bol, L. J. F. Hofmeyer,
R. M. J. Liskamp, Bioorg. Med. Chem. 1999, 7, 1043–1047.
D. W. P. M. Lowik, R. M. J. Liskamp, Eur. J. Org. Chem. 2000,
1219–1228.
E. Juaristi, H. Lopez-Ruiz, Curr. Med. Chem. 1999, 6, 983–
1004.
S. Abele, D. Seebach, Eur. J. Org. Chem. 2000, 1–15.
T. Wirth in Organic Synthesis Highlights (Ed.: H.-G. Schmalz),
Wiley-VCH, Weinheim, 2000, vol. IV, pp. 26–33.
Y. Ohfune, T. Shinada, Bull. Chem. Soc. Jpn. 2003, 76, 1115–
1129.
J. X. Huang, D. M. Du, J. X. Xu, Synthesis 2006, 315–319.
2.94 (s, 2 H, CH2), 2.77 (s, 2 H, CH2), 1.16 (s, 3 H, CH3) ppm. 13
C
[4]
[5]
[6]
[7]
NMR (50.3 MHz, D2O, DMSO as internal standard): δ = 137.4,
133.0, 130.6, 129.3, 60.5, 54.8, 47.7, 26.1 ppm. IR: ν = 3469.9 (br.,
˜
NH & OH), 1169.9 (SO2) cm–1. MS (ESI): m/z = 230 [M + H]+.
HRMS: calcd. for C10H16NO3S [M + H] 230.0845; found 230.0849.
2-Amino-2-methylpropanesulfonic Acid (9d): Colorless crystals, m.p.
325 °C (dec.) [ref.[14] 325 °C (dec.)], yield 99%. Rf = 0.08 (chloro-
1
form/methanol, 4:1; silica gel plate). H NMR (200 MHz, D2O): δ
[8]
[9]
= 3.02 (s, 2 H, CH2), 1.29 (s, 6 H, 2 CH3) ppm. 13C NMR
(50.3 MHz, D2O, DMSO as internal standard): δ = 59.7, 54.0,
27.1 ppm.
[10]
(1-Amino-1-cyclohexane)methanesulfonic Acid (9e): Colorless crys-
tals, m.p. 331 °C (dec.) [ref.[14] 331 °C (dec.)], yield 87%. Rf = 0.15
(chloroform/methanol, 4:1; silica gel plate). 1H NMR (200 MHz,
D2O): δ = 3.13 (s, 2 H, CH2), 1.88–1.73 (m, 2 H in 2 CH2), 1.57–
1.10 (m, 8 H, 2 CH2 & 2 H in 2 CH2) ppm. 13C NMR (50.3 MHz,
D2O, DMSO as internal standard): δ = 57.0, 55.5, 35.4, 25.8,
22.7 ppm.
[11]
[12]
D. Braghiroli, M. Di Bella, Tetrahedron Lett. 1996, 37, 7319–
7322.
W. Koller, A. Linkies, H. Rehling, D. Reuschling, A.-G.
Hoechst, Tetrahedron Lett. 1983, 24, 2131–2134.
L. B. Hu, H. Zhu, D. M. Du, J. X. Xu, J. Org. Chem. 2007, 72,
4543–4546.
[13]
[14]
2-Amino-2,2-diphenylethanesulfonic Acid (9f): Colorless crystals,
m.p. 239–242.5 °C (dec), yield 31% from 7f; yield 87% from 8f.
Rf = 0.26 (chloroform/methanol, 4:1; silica gel plate). 1H NMR
(200 MHz, D2O): δ = 7.28–6.92 (m, 10 H, Ph), 3.77 (s, 2 H, CH2)
ppm. 13C NMR (75.5 MHz, D2O, DMSO as internal standard): δ
[15]
[16]
J. X. Xu, S. Xu, Synthesis 2004, 276–279.
J. X. Huang, F. Wang, D. M. Du, J. X. Xu, Synthesis 2005,
2122–2128.
[17]
F. M. Cordero, M. Cacciarini, F. Machetti, F. De Sarlo, Eur. J.
Org. Chem. 2002, 1407–1411.
J. X. Xu, S. Xu, Heteroat. Chem. 2005, 16, 466–471.
J. X. Xu, Tetrahedron: Asymmetry 2002, 13, 1129–1134.
R. E. Steiger, Org. Synth. 1944, 24, 9–12.
M. J. McKennon, A. I. Meyers, K. Drauz, M. Schwarm, J. Org.
Chem. 1993, 58, 3568–3571.
H. Higashiura, H. Morino, H. Matsuura, Y. Toyomaki, K. Ien-
aga, J. Chem. Soc. Perkin Trans. 1 1989, 1479–1481.
P. D. Skelly, W. J. Ray Jr., J. W. Timberlake, J. Org. Chem. 1985,
50, 267–268.
W. R. Dunnavant, F. L. James, J. Am. Chem. Soc. 1956, 78,
2740–2743.
Y. St-Denis, S. Levesque, B. Bachand, J. J. Edmunds, L. Leb-
lond, P. Preville, M. Tarazi, P. B. Winocour, M. A. Siddiqui,
Bioorg. Med. Chem. Lett. 2002, 12, 1181–1184.
S. L. Deng, D. Z. Liu, Synthesis 2001, 2445–2447.
F. Diness, J. Beyer, M. Meldal, QSAR Comb. Sci. 2004, 23,
130–144.
= 147.1, 130.4, 129.3, 128.4, 62.2, 61.8 ppm. IR: ν = 3424.1 (br.,
˜
[18]
[19]
[20]
[21]
NH & OH), 1178.8 (SO2) cm–1. MS (ESI): m/z = 300 [M +
Na]+. HRMS: calcd. for C14H15NNaO3S [M + Na] 300.0664;
found 300.0667.
2,2-Diphenylethanesulfonic Acid (10f):[25] Colorless crystals, m.p.
93–95 °C. Rf = 0.25 (chloroform/methanol, 4:1; silica gel plate). 1H
NMR (300 MHz, D2O): δ = 7.25–7.04 (m, 10 H, Ph), 4.36 (t, J =
7.0 Hz, 1 H, CH), 3.56 (d, J = 7.0 Hz, 2 H, CH2) ppm. 13C NMR
(75.5 MHz, D2O, DMSO as internal standard): δ = 145.4, 130.8,
[22]
[23]
[24]
[25]
129.4, 128.7, 57.4, 49.3 ppm. IR: ν = 3373.0 (br., OH), 1171.3 (SO )
˜
2
cm–1. MS (ESI): m/z = 261 [M – H]–.
2,2-Diphenylethyl Thioacetate(11f):[25] Colorless crystals, m.p.
100.5–101.5 °C. Rf = 0.48 [petroleum ether (60–90 °C)/ethyl acetate,
1
20:1; silica gel plate]. H NMR (300 MHz, CDCl3): δ = 7.35–7.20
[26]
[27]
(m, 10 H, Ph), 4.17 (t, J = 8.1 Hz, 1 H, CH), 3.57 (d, J = 8.1 Hz,
2 H, CH2), 2.27 (s, 3 H, CH3) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 195.5, 142.7, 128.5, 127.9, 126.7, 50.6, 34.4, 30.6 ppm. IR: ν =
˜
Received: August 26, 2007
Published Online: November 12, 2007
1678.2 (C=O) cm–1. MS (ESI): m/z = 257 [M + H]+.
Eur. J. Org. Chem. 2008, 350–355
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
355