Convenient one-pot synthesis of sulfonamides and sulfonyl azides from thiols using N -chlorosuccinimide

Article abstract of DOI:10.1055/s-0030-1261232

A convenient synthesis of sulfonamides and sulfonyl azides from thiols is described. In situ preparation of sulfonyl chlorides from thiols is accomplished by oxidation with N-chlorosuccinimide (NCS), tetrabutylammonium chloride, and water. The sulfonyl chlorides are then further allowed to react with excess amine or sodium azide in the same reaction vessel. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1261232

LETTER
2315
Convenient One-Pot Synthesis of Sulfonamides and Sulfonyl Azides from
Thiols Using N-Chlorosuccinimide
S
ynthesis of Sulfo
o
namides
a
nd
j
Sulfon
a
yl
A
zides t Veisi,*a,b Ramin Ghorbani-Vaghei,c Saba Hemmati,a Jafar Mahmoodic
a
Department of Chemistry, Payame Noor University, 19395-4697 Tehran, I. R. of Iran
Fax +98(838)4227463; E-mail: hojatveisi@yahoo.com
b
c
Young Researchers Club, Kermanshah Branch, Islamic Azad University, Kermanshah, Iran
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
Received 19 June 2011
olefins,15 the radical amination,16 and metal-catalyzed
coupling reactions.17 Owing to a wide range of applica-
tions, a general and convenient access to sulfonyl azides
is highly desirable.
Abstract: A convenient synthesis of sulfonamides and sulfonyl
azides from thiols is described. In situ preparation of sulfonyl chlo-
rides from thiols is accomplished by oxidation with N-chlorosuccin-
imide (NCS), tetrabutylammonium chloride, and water. The
sulfonyl chlorides are then further allowed to react with excess
amine or sodium azide in the same reaction vessel.
The most practical laboratory method for preparing sulfo-
nyl azides involves the reaction of sulfonyl chlorides with
azides.18 The reaction requires the availability of sulfonyl
chlorides, which are troublesome to prepare and handle.
Generally, sulfonyl chlorides are prepared by treating sul-
fonic acids with chlorinating agents such as SOCl2,19
POCl2,20 PCl5,21 triphosgene,22 and cyanuric chloride.23 A
convenient one-pot synthesis of sulfonyl azides from sul-
fonic acids was reported by Jang and et al.24
Key words: N-chlorosuccinimide, sulfonyl chlorides, sulfon-
amides, sulfonyl azides
Sulfonamides (sulfa drugs) were the first drugs largely
employed and systematically used as preventive and che-
motherapeutic agents against various diseases.1 They are
utilized as antihypertensive,2a antiglaucoma,2b antibacteri-
al,2c antiviral,2d antiprotozoal,2e antifungal,2f antitumor,2g
anti-inflammatory,2h and anticonvulsant agents.2h They
are also effective for the treatment of urinary, intestine,
and ophthalmic infections,2i scalds,2i ulcerative colitis,2i
rheumatoid arthritis,2j male erectile dysfunction,2k and
obesity.2l The synthesis of sulfonamides also represents a
useful strategy for the protection of primary and second-
ary amines.3 Furthermore, sulfonamides are employed as
herbicides,4a plaguicides,4b pesticides,4c and surfac-
tants.4c,d
Herein, as part of our ongoing study on the application of
N-halo reagents in organic synthesis,25–29 we would like to
present the direct convenient one-pot synthesis of sulfona-
mides and sulfonyl azides from thiols using N-chlorosuc-
cinimide (NCS) under mild conditions (Scheme 1).
R1
R2
O
S
R1R2NH
r.t.
R
N
O
R1 = H, Alk, Ar
t-Bu4NCl (4 equiv)
H2O (2.5 equiv)
O
S
R
2 = Alk, Ar
R
Cl
RSH
Frequently, sulfonamides are formed from a sulfonyl
chloride and a primary or secondary amine. In turn, sulfo-
nyl chlorides can be prepared from the corresponding thi-
ols using a number of methods, commonly by bubbling
Cl2 gas into aqueous acid or a biphasic mixture containing
the thiol.5–9 Although this methodology is relatively gen-
eral, issues associated with the use of excess oxidant and/
or aqueous acid have prompted the development of alter-
native methods.10,11 We describe an oxidation–substitu-
tion sequence that is mild and minimizes both the amount
of oxidant required and the aqueous component. Recently,
the direct oxidative conversion of thiols into sulfonamides
with H2O2–SOCl2 was reported by Bahrami and et al.12
NCS (3 equiv)
MeCN
O
O
NaN3
r.t.
R
S
N3
O
Scheme 1
Initially, we surmised that it might be possible to generate
controlled amounts of Cl2 in nonprotic organic solvents by
mixing a tetraalkylammonium chloride salt with N-chlo-
rosuccinimide (NCS). We were pleased to find that treat-
ment of tetrabutylammonium chloride (3 equiv), H2O (2.5
equiv) with NCS (3 equiv) in MeCN (20 min, r.t.) provid-
ed a light yellow solution as a good oxidizing chlorinating
system to synthesize benzylsolfunyl chlorides from ben-
zyl thiol under mild conditions (Scheme 2).
Sulfonyl azides are versatile reagents for a variety of
chemical transformations. They have been used as valu-
able reagents for the preparation of a-diazocarbonyl re-
agents,13 the hydroazidation of olefins,14 the aziridation of
t-Bu4NCl (4 equiv)
H2O (2.5 equiv)
O
S
Cl
SH
SYNLETT 2011, No. 16, pp 2315–2320
x
x
.x
x
.2
0
1
1
NCS (3 equiv)
MeCN, 20 min
O
Advanced online publication: 13.09.2011
DOI: 10.1055/s-0030-1261232; Art ID: B11411ST
© Georg Thieme Verlag Stuttgart · New York
98%
Scheme 2

2316
H. Veisi et al.
LETTER
Based on this result, we would like to use this system for of structurally different thiols and amines (commercially
the in situ preparation of sulfonyl chlorides from thiols to available) under these optimized conditions. A combina-
synthesize sulfonamides in one-pot. Subsequent addition torial library (parallel format) of sulfonamides was
of a primary or secondary amine afforded the desired sul- smoothly prepared in good to high yields, and the results
fonamide. To optimize the reaction conditions, the reac- are summarized in Table 1. Aryl thiols carrying either
tion of benzyl thiol and benzylamine was selected as electron-donating or electron-withdrawing substituents
model substrate in acetonitrile at room temperature. Re- reacted very well to give the corresponding sulfonamides
painting the reaction of benzyl thiol (1 equiv), t-Bu4NCl with equal efficiency. Also, aryl amines appeared to be in-
(3 equiv), H2O (2.5 equiv) with NCS (3 equiv) in MeCN sensitive to substitution. Primary and secondary alkyl
(20 min, r.t.) and continue addition of benzylamine (4 amines and also ammonia undergo this reaction with
equiv, 20 min) gave the corresponding sulfonamide in equal efficiency. 1-Butanethiol (Table 1, entry 12) was
98% yield.
also oxidized efficiently.
Encouraged by our initial studies, we then investigated the
generality and versatility of this procedure using a series
Table 1 Synthesis of Various Sulfonamides from Thiols and Amines
Entry
Thiol
Sulfonamide
Time (h)
0.7
Yield (%)a
98
O
S
H
SH
1
N
O
O
H
SH
2
3
4
N
1
96
98
90
S
O
O
S
H
SH
N
0.7
1
O
SH
O
S
H
N
O
O
SH
SH
5
6
1
98
98
S
N
O
O
H
N
1.2
S
O
SH
O
S
H
7
8
2
90
96
N
O
SH
SH
O
S
H
N
1.5
O
O
9
2
96
S
N
O
Synlett 2011, No. 16, 2315–2320 © Thieme Stuttgart · New York

LETTER
Synthesis of Sulfonamides and Sulfonyl Azides
2317
Table 1 Synthesis of Various Sulfonamides from Thiols and Amines (continued)
Entry
10
Thiol
Sulfonamide
Time (h)
2
Yield (%)a
OMe
SH
O
S
H
94
90
90
N
MeO
MeO
O
O
S
11
12
2
SH
N
O
N
O
OMe
O
S
H
1.5
N
SH
O
O
SH
13
14
1
1
98
96
S
N
H
O
O
S
SH
N
H
O
Cl
O
S
SH
15
16
1.2
1
90
98
N
H
O
O
SH
Br
S
N
H
Br
O
O
SH
NH2
17
1
96
S
O
O
S
SH
18
19
1
1
90
98
MeO
NH2
MeO
O
O
S
SH
N
O
a Products were characterized from their physical properties, comparison with authentic samples, and by spectroscopic methods.
The present system was further examined for the synthesis ric disulfide (II). Then the successive oxidation of both
of sulfonyl azides with excellent yield from thiols, and the sulfur atoms of the disulfide molecule by chlorine produc-
results are summarized in Table 2 (entries 1–8). We de- es the intermediate (III) that undergoes rapid isomeriza-
veloped a one-pot process for preparing sulfonyl azides tion to the thiosulfonate (IV), which can easily furnish
from thiols with N-chlorosuccinimide (NCS), tetrabutyl- sulfonyl chloride (V). Then, the sulfonyl chloride (V) re-
ammonium chloride, and water. The reaction provides acts with amine or azide to form the corresponding sul-
convenience, efficiency, and generality for the prepara- fonamides (VI) or sulfonyl azides (VII).
tion of sulfonyl azides from various thiols. Employing
In summary, we have developed a mild, one-pot synthetic
less toxic reagents make this process attractive from the
method for the preparation of alkyl and aryl sulfonamides
standpoint of environment.
from thiols in the presence of primary and secondary
The possible mechanism for this transformation is shown amine using N-chlorosuccinimide (NCS) tetrabutylam-
in Scheme 3.12 Molecular chlorine generated from NCS monium chloride–water system in acetonitrile. Also, we
and t-Bu4NCl effects the oxidative chlorination. It is ac- have developed a one-pot process for preparing sulfonyl
ceptable to assume that the thiol can chlorinate in the pres- azides from thiols under these conditions in the presence
ence of chlorine. Therefore, the mechanism proceeds of NaN3. The advantages are excellent yields, the cheap-
through hydroxylation of thiol leading to the formation of ness and availability of the reagents, easy and clean work-
sulfenic acid (I), which gives the corresponding symmet- up, extremely fast reaction, high chemoselectivity, and
Synlett 2011, No. 16, 2315–2320 © Thieme Stuttgart · New York

2318
H. Veisi et al.
LETTER
O
Table 2 Synthesis of Various Sulfonyl Azides from Thiol
RSH
t-Bu4NCl
MeCN
RS Cl
H2O
Cl2
N Cl
Entry Thiol
Sulfonyl azidea
Time Yield
(min) (%)a
– HCl
O
O
RS OH
NH
I
O
SH
N3
O
1
2
45
9824
S
HCl
Cl
– Cl–
RSH
+
Cl2
O
R
S
SR
RS SR
II
RS OH
H2O
+
– H2O
– HCl
O
S
SH
60
45
60
45
90
9824
9824
9224
9524
8824
N3
Cl
O
O
S
O
O
O
Cl2
R
S
SR
– HCl
O
SH
SH
R
SR
R
S
SR
R
S
S
R
O
3
III
S
H
N3
O
IV
MeO
O
– RSH
O
O
S
R1
R2
R1R2NH
O
S
HCl
R
Cl
R
S
N
4
MeO
Cl
N3
O
V
O
VI
MeO
O
R
R
1 = H, Alk, Ar
2 = Alk, Ar
O
S
NaN3
N3
SH
5
N3
O
S
Cl
O
R
O
SH
6
O
VII
O2N
S
N3
O2N
O
Scheme 3
N3
S
SH
O
O
7
8
45
70
9024
and the corresponding pure sulfonamide was obtained as a crystal-
line solid. Recrystallization from a mixture of EtOH and H2O af-
fords analytically pure product.
O
S
General Procedures for the Conversion of Thiols to Sulfonyl
Azides
8524
N3
SH
O
To a stirred mixture of thiol compound (1 mmol), t-BuNCl (4
mmol), and H2O (2.5 mmol) in MeCN (5 mL) at 0 °C, NCS (3
mmol) was added as a solid in portions over 1–2 min. After 30 min,
NaN3 (2.2 mmol) was added to the mixture over 1–2 min. The re-
sulting mixture was stirred at r.t. for 3 h. The mixture was diluted
with CH2Cl2 (15 mL) and washed with H2O (5 mL). The organic
layer was dried over anhyd MgSO4. After filtration the solvent was
removed, and the residue was purified with column chromatogra-
phy on SiO2 (hexanes–EtOAc, 20:1) to give sulfonyl azide in good
to excellent yields.
a Products were characterized from their physical properties, compar-
ison with authentic samples, and by spectroscopic methods.
operation at room temperature. No side reactions/products
were observed during the course of the reaction, thus, we
believe that the present methodology opens new possibil-
ities for medicinal chemistry and material sciences and
could be an important addition to the existing methodolo-
gies.
Analytical Data for Selected Compounds (Table 1)
Product 1
IR (KBr): 1138, 1310 (SO2), 3287 (NH) cm–1. 1H NMR (200 MHz,
All commercially available chemicals were obtained from Merck
and Fluka companies and used without further purifications unless
otherwise stated. 1H NMR spectra were recorded on a Jeol 200 MHz
FT NMR spectrometer using TMS as internal standard and chemi-
cal shift are in d (ppm). Infrared (IR) was conducted on a Perkin
Elmer GX FT-IR spectrometer. All yields refer to isolated products.
CDCl3): d = 4.13 (s, 2 H), 4.21 (s, 2 H), 7.25–7.38 (m, 10 H). 13
C
NMR (50 MHz, CDCl3): d = 47.6, 59.3, 128.0, 128.1, 128.5, 128.8,
129.1, 130.6, 133.3, 136.8.
Product 2
IR (KBr): 1134, 1309 (SO2), 3220 (NH) cm–1.1H NMR (200 MHz,
CDCl3): d = 2.21 (s, 3 H), 4.17 (s, 2 H), 4.28 (s, 2 H), 7.20–7.58 (m,
9 H). 13C NMR (50 MHz, CDCl3): d = 24.3, 47.4, 59.8, 128.0, 128.1,
128.3, 128.6, 129.3, 130.6, 135.4 136.9.
General Procedures for the Conversion of Thiols to sulfon-
amides
To a stirred mixture of thiol compound (1 mmol), t-BuNCl (4
mmol), and H2O (2.5 mmol) in MeCN (10 mL) at 0 °C, NCS (3
mmol) was added as a solid in portions over 1–2 min. After 30 min,
amine (1 mmol) was added to the mixture over 1–2 min. The result-
ing mixture was stirred at r.t. until TLC showed complete disap-
pearance of starting material (Table 1). The mixture was filtered
and rinsed twice with MeCN (10 mL). The filtrate was evaporated,
Product 3
IR (KBr): 1118, 1308 (SO2), 3288 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 1.36–1.91 (m, 8 H), 3.56–3.62 (m, 1 H), 4.22 (s, 2 H),
7.26–7.47 (m, 5 H). 13C NMR (50 MHz, CDCl3): d = 23.1, 33.9,
55.7, 59.2, 128.6, 128.7, 129.5, 130.7.
Synlett 2011, No. 16, 2315–2320 © Thieme Stuttgart · New York

LETTER
Synthesis of Sulfonamides and Sulfonyl Azides
2319
Product 5
2 H). 13C NMR (50 MHz, CDCl3): d = 55.6, 114.2, 128.6, 133.6,
IR (KBr): 1125, 1317 (SO2) cm–1. 1H NMR (200 MHz, CDCl3): d =
4.03 (s, 4 H), 4.20 (s, 2 H), 7.29–7.38 (m, 15 H). 13C NMR (50 MHz,
CDCl3): d = 40.9, 69.0, 127.6, 128.3, 128.7, 129.0, 129.3, 131.3,
132.5, 134.8.
163.1.
Acknowledgment
We are thankful to Iran National Science Foundation (INSF) and
Payame Noor University (PNU) for partial support of this work.
Product 6
IR (KBr): 1136, 1309 (SO2), 3242 (NH) cm–1. 1H NMR 200 MHz,
CDCl3): d = 2.32 (s, 3 H), 4.07 (s, 2 H), 4.17 (s, 2 H), 7.10–7.20 (m,
6 H), 7.26–7.43 (m, 5 H). 13C NMR (50 MHz, CDCl3): d = 23.1,
33.4, 55.2, 122.4, 127.4, 128.3, 129.2, 129.4, 132.1, 134.7, 137.6.
References
(1) Hansch, C.; Sammes, P. G.; Taylor, J. B. Comprehensive
Medicinal Chemistry, Vol. 2; Pergamon Press: Oxford,
1990, Chap. 7.1.
Product 7
IR (KBr): 1160, 1325 (SO2), 3323 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 4.16 (s, 2 H), 5.24 (s, 1 H), 7.10–7.20 (m, 5 H), 7.56–
7.64 (m, 2 H), 7.65–7.95 (m, 4 H), 8.44 (s, 1 H). 13C NMR (50 MHz,
CDCl3): d = 47.3, 122.3, 127.5, 127.8, 128.6, 128.8, 129.2, 129.3,
129.5, 132.1, 134.8, 136.2, 136.6.
(2) (a) Kanda, Y.; Kawanishi, Y.; Oda, K.; Sakata, T.; Mihara,
S.; Asakura, K.; Kanemasa, T.; Ninomiya, M.; Fujimoto,
M.; Kanoike, T. Bioorg. Med. Chem. 2001, 9, 897.
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A.; Casini, A.; Supuran, C. T. Bioorg. Med. Chem. Lett.
2001, 11, 1787. (c) Bhusari, K. P.; Khedekar, P. B.; Umathe,
S. N.; Bahekar, R. H.; Rao, A. R. R. Indian J. Heterocycl.
Chem. 2000, 9, 213. (d) Eckenberg, P.; Reefschläger, J.;
Bender, W.; Goldmann, S.; Härter, M.; Hallenberger, S.;
Keldenich, J.; Weber, O.; Henninger, K. DE19934272,
2001; Chem. Abstr. 2001, 134, 115865. (e) Chibale, K.;
Haupt, H.; Kendrick, H.; Yardley, V.; Saravanamuthu, A.;
Fairlamb, A. H.; Croft, S. L. Bioorg. Med. Chem. Lett. 2001,
11, 2655. (f) Rahavi Ezabadi, I.; Camoutsis, C.;
Product 8
IR (KBr): 1155, 1325 (SO2), 3273 (NH) cm–1.1H NMR (200 MHz,
CDCl3): d = 1.25–1.76 (m, 8 H), 3.59–3.68 (m, 1 H), 5.08 (s, 1 H),
7.56–7.63 (m, 2 H), 7.67–7.98 (m, 4 H), 8.48 (s, 1 H). 13C NMR (50
MHz, CDCl3): d = 21.1, 47.33, 123.0, 126.2,128.1, 128.6, 128.7,
129.3, 129.4, 130.7, 132.3, 134.0, 137.0, 137.6.
Product 9
IR (KBr): 1157, 1329 (SO2) cm–1. 1H NMR (200 MHz, CDCl3): d =
4.38 (s, 4 H), 7.09–7.66 (m, 10 H), 7.78–7.98 (m, 6 H), 8.39 (s, 1
H). 13C NMR (50 MHz, CDCl3): d = 50.5, 123.4, 127.6, 128.3,
128.6, 128.7, 129.0, 129.3, 131.3, 132.5, 134.8.
Zoumpoulakis, P.; Geronikaki, A.; Soković, M.;
Glamočilija, J.; Čirič, A. Bioorg. Med. Chem. 2008, 16,
1150. (g) Lavoie, R.; Bouchain, G.; Frechette, S.; Woo,
S. H.; Khalil, E. A.; Leit, S.; Fournel, M.; Yan, P. T.;
Trachy Bourget, M.-C.; Beaulieu, C.; Li, Z.; Besterman, J.;
Delorme, D. Bioorg. Med. Chem. Lett. 2001, 11, 2847.
(h) Kleeman, A.; Engel, J.; Kutscher, B.; Reichert, D.
Pharmaceutical Substances, 3rd ed.; Thieme: Stuttgart,
1999. (i) Wilson, C. O.; Gisvold, O.; Block, J. H. Wilson and
Gisvold’s Textbook of Organic Medicinal and
Product 10
IR (KBr): 1154, 1325 (SO2), 3280 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 3.79 (s, 3 H), 3.91 (s, 3 H), 4.08 (d, 2 H), 4.58 (t, 1 H),
6.82 (d, 2 H), 6.97 (d, 2 H), 7.14 (d, 2 H), 7.82 (d, 2 H). 13C NMR
(50 MHz, CDCl3): d = 46.8, 55.3, 55.6, 114.1, 114.3, 128.4, 129.3,
129.3, 131.6, 159.4, 163.0.
Pharmaceutical Chemistry, 11th ed.; Block, J.; Beale, J. M.,
Eds.; Lippincott Williams and Wilkins: Philadelphia, 2004.
(j) Levin, J. I.; Chen, J. M.; Du, M. T.; Nelson, F. C.; Killar,
L. M.; Skala, S.; Sung, A.; Jin, G.; Cowling, R.; Barone, D.;
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Lee, J. Y.; Lee, N.; Ryu, D. H.; Kim, J.-S.; Lee, S.; Choi,
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T.-K. Bioorg. Med. Chem. 2001, 9, 3013. (l) Hu, B.;
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T.; Sum, F.-W.; Tillett, J.; Wong, V. Bioorg. Med. Chem.
2001, 9, 2045.
Product 11
IR (KBr): 1126, 1335 (SO2), 3275 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 3.36 (t, 4 H), 3.78 (t, 4 H), 7.56–7.49 (m, 1 H), 7.96 (m,
2 H), 8.75–8.75 (m, 1 H). 13C NMR (50 MHz, CDCl3): d = 46.7,
66.4, 123.1, 126.8, 138.0, 150.1, 156.1.
Product 12
IR (KBr): 1124, 1325 (SO2), 3262 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 0.95 (t, 3 H), 1.32 (m, 2 H), 1.72 (m, 2 H), 2.93 (m, 2
H), 3.80 (s, 3 H), 4.24 (d, 2 H), 4.51 (br t, 1 H), 6.89 (m, 2 H), 7.26
(m, 2 H). 13C NMR (50 MHz, CDCl3): d = 13.6, 21.5, 25.6, 46.8,
53.1, 55.4, 114.3, 129.0, 129.3, 159.6.
(3) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
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1486.
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(7) Skulnick, H. I.; Johnson, P. D.; Aristoff, P. A.; Morris, J. K.;
Lovasz, K. D.; Howe, W. J.; Watenpaugh, K. D.;
Product 14
IR (KBr): 1108, 1373 (SO2), 3258 (NH) cm–1. 1H NMR 200 MHz,
CDCl3): d = 2.36 (s, 3 H), 6.95–7.06 (m, 2 H), 7.15–7.22 (m, 4 H),
7.60–7.62 (m, 3 H). 13C NMR (50 MHz, CDCl3): d = 22.5, 122.8,
125.5, 126.3, 127.9, 128.3, 129.8, 130.2, 133.9, 136.3, 144.8.
Product 16
IR (KBr): 1155, 1386 (SO2), 3242 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 1.20 (m, 5 H), 1.54–1.79 (m, 5 H), 3.22 (m, 1 H), 4.98
(d, 1 H, NH), 7.72 (d, 2 H), 7.81 (d, 2 H). 13C NMR (50 MHz,
CDCl3): d = 24.8, 25, 33.8, 52.7, 127.3, 128.6, 132.3, 140.6.
Janakiraman, M. N.; Anderson, D. J.; Reischer, R. J.;
Schwartz, T. M.; Banitt, L. S.; Tomich, P. K.; Lynn, J. C.;
Horng, M.-M.; Chong, K.-T.; Hinshaw, R. R.; Dolak, L. A.;
Product 18
IR (KBr): 1115, 1329 (SO2), 3278 (NH) cm–1. 1H NMR (200 MHz,
CDCl3): d = 3.83 (s, 3 H), 4.73 (br s, 2 H), 6.96 (m, 2 H), 7.82 (m,
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Synlett 2011, No. 16, 2315–2320 © Thieme Stuttgart · New York