NaClO2-mediated preparation of pyridine-2-sulfonyl chlorides and synthesis of chiral sulfonamides

Article abstract of DOI:10.1080/17415993.2020.1775834

A simple method to prepare azaarenesulfonyl chlorides by NaClO₂-mediated oxidative chlorination of azaarenethiols have been developed, with water as the solvent. Easy purification by simple extraction and concentration gives the products in good yields. The azaarenesulfonyl chlorides readily undergo condensation with chiral amines to afford chiral sulfonamides.

Full text of DOI:10.1080/17415993.2020.1775834

Journal of Sulfur Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
NaClO2-mediated preparation of pyridine-2-
sulfonyl chlorides and synthesis of chiral
sulfonamides
Dong Xu , Shiyi Yang , Aijun Gao & Zhanhui Yang
To cite this article: Dong Xu , Shiyi Yang , Aijun Gao & Zhanhui Yang (2020): NaClO2-mediated
preparation of pyridine-2-sulfonyl chlorides and synthesis of chiral sulfonamides, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2020.1775834
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2020.1775834
NaClO2-mediated preparation of pyridine-2-sulfonyl chlorides
and synthesis of chiral sulfonamides
Dong Xu, Shiyi Yang, Aijun Gao and Zhanhui Yang
State Key Laboratory of Chemical Resource Engineering, College of Chemistry and College of Materials
Science and Engineering, Beijing University of Chemical Technology, Beijing, People’s Republic of China
ABSTRACT
ARTICLE HISTORY
Received 5 December 2019
Accepted 21 May 2020
A simple method to prepare azaarenesulfonyl chlorides by NaClO2-
mediated oxidative chlorination of azaarenethiols have been devel-
oped, withwaterasthesolvent. Easypurificationbysimpleextraction
and concentration gives the products in good yields. The azaarene-
sulfonyl chlorides readily undergo condensation with chiral amines
to afford chiral sulfonamides.
KEYWORDS
Azaarenesulfonyl chloride;
oxidative chlorination;
azaarenethiol; chiral
sulfonamides;
pyridine-2-thiol
1. Introduction
Pyridine-2-sulfonyl groups have found wide applications in both organic syntheses and
medicinal chemistry. From a synthetic perspective, they are widely used as directing groups
2
−
in transition-metal-catalyzed sp C H activation of arylamines and azaarenes[1–8], as
3
−
well as sp C H activation of amino acids or aliphatic amines, by forming bidentate 2-
pyridinesulfonamide derivatives [9–11]. In addition, 2-pyridinesulfonyl groups play an
important role in some stereoselective reactions such as Arrayás and Carretero’s anti-
stereocontrolled ring-opening of azabicyclic alkenes [12] and Toru’s enantioselective
−
C C bond formation to sulfonylimines [13]. Some useful reagents such as Hu’s diflu-
oromethylation reagent [14–16] and Doyle’s deoxyfluorination reagent [17] also have a
pyridine-2-sulfonyl group as a key structural motif. In medical chemistry, various reports
have demonstrated that the drug candidates with N-pyridinesulfonyl groups display good
CONTACT Aijun Gao
gaoaj@mail.buct.edu.cn; Zhanhui Yang
zhyang@mail.buct.edu.cn
State Key
Laboratory of Chemical Resource Engineering, College of Chemistry and College of Materials Science and Engineering,
Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China
This article makes reference to supplementary material available on the publisher’s website at
https://doi.org/10.1080/17415993.2020.1775834
© 2020 Informa UK Limited, trading as Taylor & Francis Group

2
D. XU ET AL.
bioactivities [18–20], 2-Pyridinesulfonyl chlorides are the most important precursors to
introduce the pyridinesulfonyl groups, and their syntheses have received much attention.
Generally, oxidative chlorination of 2-thiopyridines with aqueous sodium hypochlorite
solution (bleach) [21–23], in addition to chlorine gas [24–26] and Oxone-KCl [27], is
always harnessed to achieve this goal. However, as demonstrated by Pu’s [28] and our
groups [29], the instability of bleach and the ambiguous content of efficient chlorine some-
times cause disappointed results, and titration is always recommended before use. In
addition, the low chlorium content in bleach and a largely excessive amount of water also
renders the large-scale operation less convenient. To overcome this problem, Pu and co-
workers turned to 2,4-dichloro-5,5-dimethyl hydantoin, and organic waste was generated
as byproduct [28]. Out of our background in developing new reactions via oxidation of low-
valent organosulfur compounds with halogenium oxidants [29–37], we turned to the solid
sodium chlorite, which has already been evidenced as efficient oxidizing reagent to convert
aldehydes to carboxylic acids [38,39] and S-alkyl isothiourea salts into the corresponding
sulfonyl chlorides [30]. In this work, by use of sodium chlorite, we have developed a clean
and more efficient synthesis of 2-pyridinesulfonyl chlorides, and have demonstrated their
application in synthesizing some chiral sulfonamides.
2. Results and discussion
According to the optimal conditions in our previous work [30], we initially tried the reac-
tion on a 1-mmol scale, by dissolving 2-thiopyridines (1a) in concentrated hydrochloric
acid and subsequent addition of the aqueous sodium chlorite solution at low temperature.
The reaction was completed after 15 min upon addition of sodium chlorite, as indicated by
TLC analysis. In light of the fact that reagent NaClO2 and byproduct NaCl dissolve well in
water while the product 2-pyridinesulfonyl chloride 2a dissolves well in organic solvents,
we first tried the purification by extraction with dichloromethane, drying over Na2SO4
and then concentrated under vaccum. Gratifyingly, desired product 2a was obtained as
a colorless oil in 90% yield. We also found that a yellow solid, which was later identified
as 2-(chlorosulfonyl) pyridin-1-ium chloride, precipitated during the reaction. Another
purification in a parallel reaction by filtrating the precipitates and drying at vacuum gave
the hydrochloride salt of 2a in 48% yield. When the solid hydrochloride of 2a was dissolved
in dichloromethane and then concentrated under vacuum, dehydrochlorination occurred.
These two purifications gave the corresponding products in good purity, as indicated by
their 1H NMR spectra. As for the oxidative chlorination mechanism, our previous work
suggested that the Cl and O atoms in 2a came from sodium chlorite and water molecules,
respectively [30]. Scheme 1.
The preparation was easy to scale up. On a 20-mmol scale, 2a was prepared in a yield
of 78% (2.6 g). It is noteworthy that 2-pyridinesulfonyl chloride was not so stable. After
immediate purification, it was colorless. However, after being stored in a refrigerator at
−4°C for two days, it became yellow. After one week, it became brown. However, our fur-
ther experiments revealed that the change of color did not affect its further application
(vide post).
With the optimal procedure, 6-methylpyridine-2-sulfonyl chloride (2b) and 4-
methylpyridine-2-sulfonyl chloride (2c) were readily synthesized in satisfactory 89% and
55% yields, respectively, from the corresponding 2-thiopyridines 1b and 1c. Although we

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. Trials in synthesizing 2-pyidinesulfonyl chloride.
Figure 1. Failed examples for preparing azaarenethiols.
Figure 2. Failed examples for preparing azaarenesulfonyl chlorides.
believe that this is a good method to synthesize various substituted pyridine-2-sulfonyl
chlorides, the current substrate scope is severely limited by the deficient resources of dif-
ferent 2-thiopyridines (see Figure 1 in the Experimental section). Other heteroarenethiols
were also tested under the optimal conditions (see Figure 2 in the Experimental section).
However, only the reaction of 1-methyl-1H-imidazole-2-thiol (1d) gave desired sulfonyl
chloride 2d in 82% isolated yield, while the others gave desulfurative chlorination prod-
ucts or complex decomposed chlorination products, with complete consumption of the
heteroarenethiols. Scheme 2.
With the sulfonyl chlorides in hand, we used them in the synthesis of chiral
sulfonamides. The four azaarenesulfonyl chlorides 2a-d readily reacted with (l)−1-
phenylethylamine (3a) to deliver desired chiral sulfonamides 4aa-4da in 74-83% yields.
Next, we sought to explore the scope of chiral amines. A number of enantiopure amino acid
esters salts 3b-h were tested, using pyridine-2-sulfonyl chloride as the sulfonyl donor. The
reactions of methyl l-methioninate (3b), methyl l-valinate (3c), and methyl l-alaninate

4
D. XU ET AL.
Scheme 2. Preparation of some azaarenesulfonyl chlorides.
Table 1. Use of azaareneslfonyl chlorides to prepare chiral sulfonamidesa.
aAll the reactions were performed on 1-mmol scale, and the yields provided were isolated yields
from column chromatography on silica gel.
(3d) gave desired products 4ab, 4ac, and 4ad in 74%, 43% and 55% yields, respectively.
In addition, l-alaninate (3e), l-isoleucinate (3f), and l-phenylalaninate (3 g) also readily
underwent the condensation to give chiral sulfonamides 4ae, 4af, 4af in respective 35%,
77%, and 67% yields. Notably, the NH moiety in the indolyl ring of l-tryptophanate (3 h)
did react with 2a, while the NH2 moiety adjacent to the ester group exclusively underwent
the displacement to give 4ah in 81% yields. Table 1.
−
The synthesized chiral sulfonamides have found indispensable application in the C H
activation field. For example, Carretero and coworkers found that the direct Pd-catalyzed

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 3. Selected important applications of the chiral sulfonamides.
γ -arylation of 4af occurred readily, with the N-(2-pyridyl) sulfonyl as directing group
(Scheme 3, eqn. 1) [9]. In 2019, the same group discovered a general method to construct
seven-membered ring through cascade Pd-catalyzed γ -C(sp3)-H arylation and C(sp2)–H
carbonylation of 4ac using Mo(CO)6 as the CO source (Scheme 3, eqn. 2) [11].
3. Conclusion
We have described a simple method to prepare some azaarenesulfonyl chlorides by
NaClO2-mediated oxidative chlorination of azaarenethiols. Water is used as the sol-
vent, and the products are purified by simple extraction and concentration. Some
pyridine-2-sulfonyl chlorides and 1-methyl-1H-imidazole-2-sulfonyl chloride are suc-
cessfully obtained. The azaarenesulfonyl chlorides readily undergo condensation with
chiral amines to afford chiral sulfonamides, which serve as important substrates in C–H
activation/functionalization, with the azaaryl moieties as directing groups.
4. Experimental section
4.1. General
All the chemicals and solvents were used directly as received. TLC analyses were performed
on Yantai Chemical Co., Ltd. silica gel GF254 plates with petroleum ether (PE) and ethyl
acetate (EA), and the plates were visualized with UV light. Products were purified with col-
umn chromatography using Qingdao Ocean Chemical Co., Ltd. silica gel (200-300 mesh)
with PE and EA as eluents. Melting points were obtained on a Yanaco MP-500 melting
point apparatus and are uncorrected. The specific rotation analysis was measured by Anton
Paar MCP200 Polarimeter. IR spectra were taken on a Bruker FT-IR spectrometer on KBr
pellets. 1H and 13C spectra were recorded on a Bruker 400 MHz spectrometer as CDCl3

6
D. XU ET AL.
solution with TMS as an internal standard. HRMS data were obtained with an Agilent
LC/MS TOF mass spectrometer.
1-Methyl-1H-imidazole-2-thiol and pyridine-2-thiol are commercially available.
4.2. General procedure for the synthesis of pyridine-2-thiols
Prepared according to Thirtle’s procedure [40]. In a 25-ml dry round-bottom flask, 1 mmol
of substituted 2-fluoropyridine, 1.2 mmol of NaSH (96 mg, 70% content by weight,1.2 mol),
and 10 ml of 1,2-propylene glycol were refluxed for 2 h. The reaction was cooled to room
temperature. The system was washed with 10 ml of brine, extracted with ethyl acetate, dried
with NaSO4, and concentrated in vacuum. The resultant residue was further purified by
column chromatography on silica gel (PE:EA = 2:1) to obtain the corresponding products.
4.2.1. 4-methylpyridine-2-thiol (1b)
Known compound, CAS No. 18368-65-5. Yellow liquid; Yield 88 mg, 70%; Rf = 0.25 (PE:
1
EA = 2:1, v/v). H NMR (400 MHz, CDCl3) δ 13.6 (1H, s), 7.46 (1H, d, J = 6.4 Hz),
7.4(1H, s), 6.59 (1H, dd, J = 6.8, 1.2 Hz), 2.25 (3H, s).
4.2.2. 6-methylpyridine-2-thiol (1c)
Known compound, CAS No. 18368-57-5. Yellow liquid; Yield 62 mg, 49%; Rf = 0.3 (PE:
EA = 2:1, v/v). 1H NMR (400 MHz, CDCl3) δ 13.44 (1H, s), 7.33 (1H, d, J = 8.8 Hz), 7.23
(1H, dd, J = 6.8, 1.2 Hz), 6.47 (1H, d, J = 6.8 Hz), 2.42 (3H, s).
The reactions of the following fluoropyridines or fluoroquinolines under the above
conditions failed.
4.3. General procedure for the synthesis of sulfonyl chlorides.
To a 5-mL round-bottom flask was sequentially added azaarenethiol (2.0 mmol) and con-
centrated HCl (12 mol/L, 1.0 mL) at 0 oC in an ice bath. Subsequently, sodium chlorite
(426 mg, 85% content by weight, 4 mmol) dissolved in 1 mL of water, was added dropwise
within 15 min. To maintain the inner temperature of reaction mixture to no more than
5 oC, ice was intermittently added to the flask. After another 15 min, the reaction mixture
was extracted by CH2Cl2, dried over anhydrous Na2SO4 and concentrated in vacuum, and
the corresponding crude azaarenesulfonyl chloride was obtained.
4.3.1. Pyridine-2-sulfonyl chloride (2a)
Known compound, CAS No. 66715-65-9. Yellow liquid; Yield: 160 mg, 90%. 1H NMR (400
MHz, CDCl3) δ 8.81-8.79 (1H, m), 8.11-8.05 (2H, m), 7.72-7.68 (1H, m).
4.3.2. 6-Methylpyridine-2-sulfonyl chloride (2b)
Known compound, CAS No. 281221-71-4. Yellow liquid; Yield: 219 mg, 89%. H NMR
1
(400 MHz, CDCl3) δ 7.91 (2H, d, J = 4.8 Hz), 7.51 (1H, t, J = 4.8 Hz), 2.72 (3H, s).

JOURNAL OF SULFUR CHEMISTRY
7
4.3.3. 4-Methylpyridine-2-sulfonyl chloride (2c)
1
Known compound, CAS No. 341008-95-5. Yellow liquid; Yield: 105 mg, 55%. H NMR
(400 MHz, CDCl3) δ 8.64 (1H, d, J = 5.2 Hz), 7.91 (1H, s), 7.48 (1H, dd, J = 5.2 Hz,
0.5Hz), 2.54 (3H, s).
4.3.4. 1-Methyl-1H-imidazole-2-sulfonyl chloride (2d):
Known compound, CAS No. 55694-81-0. Yellow liquid; Yield: 296 mg, 82%. 1H NMR (400
MHz, CDCl3) δ 7.23(1H, s), 7.19 (1H, s), 4.03 (1H, s).
The reactions of the following azaarenethiols under the above conditions failed.
4.4. General procedure for the synthesis of chiral sulfonamides
To a dry 25-mL round-bottom flask was added chiral amine or chiral amino acid ester
salt (1.0 mmol) and the solution of triethylamine (222 mg, 2.2 mmol for chiral amines, or
334 mg, 3.3 mmol for amino acid ester salts) in 5 mL of CH2Cl2 at 0 °C in an ice bath.
Then a solution of azaarenesulfonyl chloride (1.1 mmol) in 2.5 mL of CH2Cl2 was added
dropwise. The mixture was slowly warmed to room temperature. Upon completion of the
reactions (detected by TLC analysis), the reaction mixture was washed by water (3 × 5 mL),
dried over MgSO4, concentrated in vacuum. The residue was further purified by column
chromatography with PE and EA as eluent to obtain the corresponding chiral sulfonamide.
4.4.1. (S)-N-(1-Phenylethyl) pyridine-2-sulfonamide (4aa)
Known compound, CAS No. 872874-24-3. White solid, mp 102-103°C, Lit.13 103.8–105.0
°C; Yield: 204 mg, 77%; Specific rotation [α]2D5 = - 44.4 (c = 0.25, CH2Cl2). Lit.13 [α]D20 =-
42.3 (c = 0.29, CHCl3). 1H NMR (400 MHz, CDCl3) δ 8.55 (1H, d, J = 4.8 Hz), 7.78-7.69
(2H, m), 7.38-7.32 (1H, m), 7.2-7.1 (5H, m), 5.53 (1H, d, J = 7.6 Hz), 4.60 (1H, qui, J = 7.2
Hz), 1.47 (1H, d, J = 6.8 Hz); 13C NMR (101 MHz, CDCl3) δ 157.8, 149.7, 141.6, 137.6,
128.4, 127.4, 126.3, 126.2, 122.1, 77.3, 77.0, 76.7, 54.2, 23.3. ESI-HRMS [M + H]+ calcd
for C13H15N2O2S+ m/z 263.0849;found, 263.0849 (these two numbers are occasionally
identical).
4.4.2. (S)-6-Methyl-N-(1-phenylethyl) pyridine-2-sulfonamide (4ba):
Transparent solid, mp 157–160 °C; Yield: 206 mg, 74%; Specific rotation [α]2D5 = + 24.0
(c = 1.0; CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 7.64-7.56 (2H, m), 7.19-7.07 (6H, m),
5.34 (1H, d, J = 7.6 Hz), 4.56 (1H, qui, J = 7.2 Hz), 2.49 (3H, s), 1.49 (3H, d, J = 6.8
Hz); 13C NMR (101 MHz, CDCl3) δ 159.4, 156.8, 141.7, 137.6, 128.2, 127.8, 127.3, 126.1,
126.1, 125.8,119.1, 54.1, 24.0, 23.4. FT-IR (film, cm−1): 3273, 2979, 2930, 1593, 1452, 1329,
1206, 1131, 1118, 1095, 965. ESI-HRMS [M + H]+ calcd for C14H17N2O2S+ m/z 277.1005;
found, 277.1002.
4.4.3. (S)-4-Methyl-N-(1-phenylethyl) pyridine-2-sulfonamide (4ca):
Transparent solid, mp: 154–156 °C; Yield: 217 mg, 78%; Specific rotation [α]2D5 = + 32.0
(c = 1.0; CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 7.63-7.57 (2H, m), 7.19-7.09 (6H, m),
5.34 (1H, d, J = 7.7 Hz), 4.56 (1H, qui, J = 7.1 Hz), 2.49 (3H, s), 1.49(3H, d, J = 6.9 Hz);
13C NMR (101 MHz, CDCl3) δ 159.4, 156.8, 141.7, 137.6, 128.2, 127.4, 126.1, 126.1, 119.1,
54.2, 24.1, 23.4. FT-IR (film, cm−1): 3275, 2976, 2928, 1594, 1452, 1329, 1206, 1128, 1117,

8
D. XU ET AL.
1090, 966 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for C14H17N2O2S+ m/z 277.1005;
found, 277.1006.
4.4.4. (S)-1-methyl-N-(1-phenylethyl)-1h-imidazole-2-sulfonamide (4da)
White solid, mp 112–114 °C; Yield: 220 mg, 83%; Specific rotation [α]2D5 = + 91.2 (c = 0.4;
CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 7.26-7.15 (5H, m), 6.97 (2H, m), 6.72 (1H, s), 4.69
(1H, qui, J = 6.4 Hz), 3.65 (3H, s), 1.51 (3H, d, J = 7.2 Hz), 13C NMR (101 MHz, CDCl3)
δ 143.8, 142.4, 128.8, 127.7, 126.5, 124.6, 54.7, 35.3, 23.5. FT-IR (film, cm−1): 3258, 3065,
2974, 2926, 2854, 1459, 1342, 1186, 1148, 302, 632 cm−1. HRMS (ESI) m/z: [M + H]+
calcd for C12H16N3O2S+ m/z 266.0958; found, 266.0960.
4.4.5. Methyl (pyridin-2-ylsulfonyl)-L-Methioninate (4ab)
White solid, mp = 91-92 °C; Yield: 225 mg, 74%; Specific rotation [α]2D5 = + 26.0
(c = 0.25, CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 8.65 (1H, d, J = 4.8 Hz), 7.97 (1H, d,
J = 8.0 Hz), 7.92 (1H, t, J = 8.0 Hz), 7.52-7.47 (1H, m), 5.77 (1H, d, J = 8.8 Hz), 4.45 (1H,
td, J = 8.4 Hz, J = 4.8 Hz), 3.62 (3H, s), 2.65-2.55 (2H, m), 2.18-2.04 (1H, m), 2.07 (3H, s),
2.01-1.91 (1H, m); 13C NMR (101 MHz, CDCl3) δ 171.8, 157.6, 149.6, 138.3, 126.8, 121.9,
77.3, 77.0, 76.7, 55.7, 52.6, 32.8, 29.6, 15.3. FT-IR (film, cm−1): 3257, 2+954, 2919, 1737,
1579, 1427, 1344, 1179. ESI-HRMS [M + H]+ calcd for C11H17N2O4S2 m/z 305.0635;
found, 305.0624.
4.4.6. Methyl (pyridin-2-ylsulfonyl)-L-Valinate (4ac)
Known compound, CAS No. 1384331-68-3. White solid, mp = 109-110 °C, Lit.9 109–109
°C; Yield: 117 mg, 43%; Specific rotation [α]2D5 = + 13.6 (c = 0.25, CH2Cl2), Lit. 9 [α]D =
+17 (c = 1, CH2Cl2, no temperature given by this ref.). 1H NMR (400 MHz, CDCl3) δ 8.62
(1H d, J = 4.4 Hz), 7.95 (1H, d, J = 7.6 Hz), 7.88 (1H, t, J = 7.6 Hz), 7.49-7.43 (1H, m),
5.43 (1H, d, J = 10.0 Hz), 4.14 (1H, dd, J = 10.0, 5.0 Hz), 3.56 (3H, s), 2.16-2.04 (1H, m),
0.99 (3H, d, J = 6.8 Hz), 0.88 (3H, d, J = 6.8 Hz); 13C NMR (101 MHz, CDCl3) δ 171.8,
157.8, 149.6, 138.0, 126.6, 121.7, 77.3, 77.0, 76.7, 62.0, 52.2, 31.7, 18.9, 17.3. ESI-HRMS
[M + H]+ calcd for C11H17N2O4S+ m/z 273.0904; found, 273.0910.
4.4.7. Methyl (pyridin-2-ylsulfonyl)-L-Alaninate (4ad)
White solid, mp = 127-128 °C; Yield: 134 mg, 55%; Specific rotation [α]2D5 = - 2.6
1
(c = 0.15, CH2Cl2). H NMR (400 MHz, CDCl3) δ 8.65 (1H, d, J = 4.0 Hz), 7.96 (1H,
d, J = 8.0 Hz), 7.89 (1H, t, J = 7.8 Hz), 7.50-7.45 (1H, m), 5.68 (1H, d, J = 10.0 Hz), 4.35
(1H, qui, J = 7.6 Hz), 3.62 (3H, s), 1.43 (1H, d, J = 7.2 Hz); 13C NMR (101 MHz, CDCl3)
δ 172.6, 157.9, 149.8, 138.0, 126.7, 121.7, 77.3, 77.0, 76.7, 52.6, 52.4, 20.1. FT-IR (film,
cm−1): 3170, 2994, 2957, 2890, 1471, 1580, 1460, 1435, 1424, 1351, 1213, 1180. ESI-HRMS
[M + H]+ calcd for C9H13N2O4S+ m/z 245.0591; found, 245.0594.
4.4.8. Methyl (pyridin-2-ylsulfonyl)-L-Leucinate (4ae)
Known compound, CAS No. 1384331-70-7. White solid, mp = 80-81 °C, Lit.9 81–83 °C;
Yield: 100 mg, 35%; Specific rotation [α]2D5 = - 5.2 (c = 0.25, CH2Cl2), Lit.9 [α]D = 0
1
(c = 1, CH2Cl2, no temperature given by this ref.). H NMR (400 MHz, CDCl3) δ 8.64
(1H, d, J = 4.8 Hz), 7.97 (1H, d, J = 8.0 Hz), 7.89 (1H, t, J = 7.6 Hz), 7.50-7.44 (1H, m),
5.36 (1H, d, J = 9.6 Hz), 4.34-4.26 (1H, m), 3.56 (3H, s), 1.84 (1H, sep, J = 6.8 Hz), 1.54

JOURNAL OF SULFUR CHEMISTRY
9
(2H, t, J = 7.2 Hz), 0.93 (6H, d, J = 6.4 Hz); 13C NMR (101 MHz, CDCl3) δ 172.8, 157.8,
149.7, 138.0, 126.6, 121.8, 77.3, 77.0, 76.7, 55.4, 52.3, 42.6, 24.3, 22.8, 21.4. ESI-HRMS
[M + H]+ calcd for C12H19N2O4S+ m/z 287.1060; found, 287.1060 (these two numbers
are occasionally identical).
4.4.9. Methyl (pyridin-2-ylsulfonyl)-L-Isoleucinate (4af)
Known compound, CAS No. 1423218-69-2. White solid, mp = 95-96 °C, Lit. 9 97–99 °C;
Yield: 220 mg, 77%; Specific rotation [α]2D5 = + 23.5 (c = 0.2, CH2Cl2), Lit. 9 [α]D = + 25
1
(c = 1, CH2Cl2, no temperature given by this ref.). H NMR (400 MHz, CDCl3) δ 8.63
(1H, d, J = 4.8 Hz), 7.96 (1H, d, J = 7.6 Hz), 7.89 (1H, t, J = 7.8 Hz), 7.50-7.42 (1H, m),
5.39 (1H, t, J = 9.4 Hz), 4.19 (1H, dd, J = 9.6, 5.2 Hz), 3.56 (3H, s), 1.87-1.80 (1H, m),
1.50-1.38 (1H, m), 1.26-1.12 (1H, m), 0.95 (3H, d, J = 7.2 Hz), 0.95 (3H, d, J = 7.4 Hz);
13C NMR (101 MHz, CDCl3) δ 171.8, 157.8, 149.7, 138.0, 126.6, 121.8, 77.3, 77.0, 76.7, 61.3,
52.1, 38.6, 24.6, 15.3, 11.3. ESI-HRMS [M + H]+ calcd for C12H19N2O4S+ m/z 287.1060;
found, 287.1062.
4.4.10. Methyl (pyridin-2-ylsulfonyl)-L-Phenylalaninate (4ag) [41]
Known compound, CAS No. 1440515-06-9. Colorless solid, mp = 79-81 °C; Yield: 173 mg,
67%; Specific rotation [α]D25 = + 17.6 (c = 0.5, CH2Cl2). H NMR (400 MHz, CDCl3)
1
δ 8.61 (1H, d, J = 4.8 Hz,), 8.12 (1H, s), 7.94-7.82 (2H, m), 7.45 (1H, t, J = 6.0 Hz),
7.28-7.19 (3H, m), 7.11 (2H, d, J = 6.4 Hz), 5.40 (1H, d, J = 8.8 Hz), 4.63 (1H, dt,
J = 8.8, 5.6 Hz), 3.56 (3H, s), 3.12 (2H, d, J = 5.6 Hz); 13C NMR (101 MHz, CDCl3)
δ 171.2, 157.8, 149.8, 138.0, 135.0, 129.4, 128.5, 127.2, 126.6, 121.6, 77.3, 77.0, 76.7,
57.5, 52.3, 39.7. ESI-HRMS [M + H]+ calcd for C15H17N2O4S+ m/z 321.0904; found,
321.0905.
4.4.11. Methyl (pyridin-2-ylsulfonyl)-L-Tryptophanate (4ah)
White solid, mp = 102-105 °C; Yield: 290 mg, 81%; Specific rotation [α]2D5 = + 7.0
(c = 0.5, CH2Cl2). 1H NMR (400 MHz, CDCl3) δ 8.53 (1H, d, J = 4.8 Hz), 8.12 (1H, s),
7.87 (1H, d, J = 7.6 Hz), 7.79 (1H, t, J = 7.6 Hz), 7.47 (1H, d, J = 8.0 Hz), 7.42-7.34 (1H,
m), 7.31 (1H, d, J = 8.0 Hz,), 7.16 (1H, t, J = 7.6 Hz), 7.10-7.03 (2H, m), 5.47 (1H, d,
J = 8.4 Hz), 4.63 (1H, dt, J = 8.4, 5.6 Hz), 3.52 (3H, s), 3.31 (2H, d, J = 5.2 Hz); 13C NMR
(101 MHz, CDCl3) δ 171.6, 157.5, 149.7, 137.8, 136.1, 127.2, 126.5, 123.4, 122.2, 121.6,
119.6, 118.5, 111.2, 109.0, 77.3, 77.0, 76.7, 56.8, 52.4, 29.5. FT-IR (film, cm−1): 3267, 3062,
2953, 2926, 1744, 1579, 1497, 1455, 1428, 1346, 1176, 1121, 745, 702. ESI-HRMS [M + H]+
calcd for C17H18N3O4S+ m/z 360.1013; found, 360.1017.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This work was financially supported by the Natural Science Foundation of Beijing Municipality (no.
2202041) and the Fundamental Research Funds for the Central Universities (nos. XK1802-6 and
12060093063). Natural Science Foundation of Beijing.

10
D. XU ET AL.
ORCID
Aijun Gao http://orcid.org/0000-0001-9594-0860
Zhanhui Yang http://orcid.org/0000-0001-7050-8780
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