Direct Synthesis of Nitrones via Transition-Metal-Free Ring-Opening of N -Tosylaziridines with the Nitrogen Atom of Various (E)-Aldoximes and (E)-Ketoximes

Article abstract of DOI:10.1055/s-0039-1690186

The KOH-, K ₂ CO ₃ -, or Et ₃ N-catalyzed ring-opening reaction of N -tosylaziridines using the nitrogen atom of a series of (E)-aldoximes and (E)-ketoximes as a nucleophilic atom instead of an oxygen atom was developed to construct various nitrones under mild reaction conditions. Diverse (E)-aldoximes and (E)-ketoximes were demonstrated to be compatible with this reaction and the products of O -ring-opening reactions were not detected for most examples.

Full text of DOI:10.1055/s-0039-1690186

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–O
paper
A
en
X. Li et al.
Paper
Synthesis
Direct Synthesis of Nitrones via Transition-Metal-Free Ring-Opening
of N-Tosylaziridines with the Nitrogen Atom of Various (E)-Aldoximes
and (E)-Ketoximes
Xing Li*
0
0
0
0-0
0
0
1-
8
0
9
6-4
4
9
9
O
N
O
N
KOH (10 mol%)
R1
R2
R3
R1
R2
R2
R1
R3
R4
OH
Wenjing Yan
Rui Zhang
N
or
N
Ts +
R4
R3
R4
NH
Ts
NH
Ts
CH3CN (0.5 mL)
Honghong Chang
Wenchao Gao
Xiuping Tian*
Wenlong Wei
R
R
3 = Ph, R4 = H, alkyl
3 = alkyl, R4 = alkyl
59 examples
up to 99% yields
up to 100% regioselectivity
R3 = Heteroaryl, R4 = Me
Department of Biomedical Engineering, Taiyuan University
of Technology, 79 West Yingze Street, Taiyuan 030024,
P. R. of China
lixing@tyut.edu.cn
txp1963@sina.com
Received: 03.06.2019
Accepted after revision: 29.07.2019
Published online: 22.08.2019
Aziridines are valuable intermediates in organic synthe-
sis because of their ability to undergo regioselective ring-
opening reactions with a wide range of nucleophiles for the
synthesis of many nitrogen-containing biologically active
molecules.10 Among these reactions, in particular the
nucleophilic ring opening of aziridines with amines contin-
ues to occupy a prominent position and attract much more
attention in synthetic organic chemistry as they furnish
very valuable 1,2-diamines.11 Notably, azides have also
been widely observed as a ring-opening reagent.12 In con-
trast to these two kinds of nitrogen nucleophiles, the ring-
opening reactions of aziridines with oximes as N-nucleop-
hiles are still rare.
DOI: 10.1055/s-0039-1690186; Art ID: ss-2019-f0309-op
Abstract The KOH-, K2CO3-, or Et3N-catalyzed ring-opening reaction
of N-tosylaziridines using the nitrogen atom of a series of (E)-aldoximes
and (E)-ketoximes as a nucleophilic atom instead of an oxygen atom
was developed to construct various nitrones under mild reaction condi-
tions. Diverse (E)-aldoximes and (E)-ketoximes were demonstrated to
be compatible with this reaction and the products of O-ring-opening
reactions were not detected for most examples.
Key words nitrone, N-tosylaziridine, oxime, KOH, ring opening
Polyfunctionalized molecular scaffolds play an import-
ant role in organic transformation. Nitrones bearing func-
tional groups containing an amino group on the nitrogen
atom are powerful structural motifs. Formal nitrones with
simple structure have been found in versatile synthetic in-
termediates and building blocks.1 As 1,3-dipolarophiles
they allow the incorporation of two heteroatoms into the
same framework and they can readily undergo various
cycloaddition reactions with diverse dipolarophiles in a sin-
gle step to construct various biologically active heterocyclic
compounds.2 Owing to these important applications, some
strategies for the construction of this class of structural core
have been extensively investigated.3 Although the oxidation
of secondary amines,4 hydroxylamines,5 or imines,6 con-
densation of carbonyl compounds with hydroxylamines,7
reactions of nitro compounds with aldehyde8 and others9
have been proven to be very general for the synthesis of ni-
trones that have simple structures on the nitrogen atom, re-
ports on the preparation of polyfunctional nitrones having
one functional group containing an amino group on the
nitrogen atom are still very scarce.
Oximes are key building blocks that exist in some in-
flammatory drugs and functional materials.13 They are also
very important synthetic intermediates. Their C=N–O moi-
ety can smoothly undergo cycloaddition reactions with
many compounds containing unsaturated bonds.14 Further-
more, the N–O units are also popular functional groups as
they can undergo various substitution reactions. Among
them, the functionalization of oxygen has been extensively
investigated to construct various oxime ethers or their de-
rivatives that are very important intermediates.15,16a In con-
trast, the introduction of diverse functional groups at the
N-position is still limited.16 In 2012/2013, Anderson and co-
workers reported that ,-unsaturated N-aryl ketonitrones
can be generated by copper-mediated N-arylation of chal-
cone oximes with arylboronic acids.17 Then in 2015, Chen,
Mo, and co-workers reported a metal-free N-arylation of
oximes with diaryliodonium salts to produce ,-unsatu-
rated N-aryl ketonitrones.18 Despite these achievements,
these methods only can provide products that are substi-
tuted by aromatic groups on the nitrogen atom of the ox-
ime. In 2001, Grigg and co-workers had reported the ring-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
X. Li et al.
Paper
Synthesis
opening reaction of aziridines with the nitrogen atom of
(Z)-oximes for the synthesis of N-alkyl oximes under a N2
atmosphere with the assistance of NaH.19 However, the re-
action was not systematically studied, and the research was
limited to the reaction of 1-[(4-chlorophenyl)sulfonyl]aziri-
dine with 6 para-substituted (Z)-aryl oximes. In addition,
the method also required the use of N2 and excessive
amounts of NaH, and the corresponding reaction yields
were less than 77%. Herein, we report a systematic study of
the direct and simple KOH-, K2CO3-, or Et3N-catalyzed ring-
opening reaction of N-tosylaziridines with the nitrogen
atom of a series of (E)-aldoximes and (E)-ketoximes for the
construction of nitrones. More importantly, only the prod-
ucts of N-ring-opening reactions were observed in most ex-
amples.
Initially, the reaction of 7-tosyl-7-azabicyclo[4.1.0]hep-
tane (1a) and benzaldehyde oxime (2a) was selected as the
model reaction to identify the best base catalyst. As sum-
marized in Table 1, the effect of various bases on the yield
was observed. It was found that KOH was the most suitable
catalyst, affording the desired product 3a in 11% yield (Table
1, entry 8). t-BuOK and Cs2CO3 gave slightly lower yields
(Table 1, entries 9 and 10). However, no desired product
was detected when other bases were employed as the cata-
lyst (Table 1, entries 1–7). The low yields are due to the low
conversion of the starting material 7-tosyl-7-azabicy-
clo[4.1.0]heptane (1a). These results also implied that the
strength of alkalinity and the type of cation determine the
activity of the catalyst. The screening of solvents revealed
that CH3CN was the optimal solvent and showed the high-
est reactivity, giving the product 3a in 99% yield (Table 1,
entry 14). EtOAc and DCE both provided the product 3a in
much lower yields (<20%, Table 1, entries 12 and 13); only a
trace amount of product 3a was obtained in CH2Cl2 (Table 1,
entry 11). The amount of solvent used did not obviously af-
fect the yield and 0.5 mL of CH3CN was the most suitable
(Table 1, entries 15 and 16 vs. 14). Encouraged by these re-
sults, we switched to the examination of temperature. Un-
fortunately, lowering the reaction temperature resulted in a
decrease in the yield of 3a (Table 1, entry 17 vs. 14). Subse-
quently, the ratio of reaction substrates was studied (Table
1, entries 14, 18, and 19). The desired product 3a was ob-
tained in 97% yield when the ratio of 7-tosyl-7-azabicyclo-
[4.1.0]heptane (1a) and benzaldehyde oxime (2a) was 1:1.2.
In summary, extensive screening showed that the opti-
mized reaction conditions are: 7-tosyl-7-azabicyclo-
[4.1.0]heptane (1a; 0.1 mmol), benzaldehyde oxime (2a;
0.12 mmol), and KOH (10 mol%) in CH3CN (0.5 mL) at 70 °C
for 6 h (Table 1, entry 19).
Table 1 Screening of Reaction Conditionsa
O
N
OH
N
Catalyst, Solvent
T, Time
N
Ts
+
NH
Ts
1a
2a
3a
Entry
Base
Solvent (mL)
Temp 2a
(°C)
Time
Yield
(%)b
(equiv) (h)
c
1
2
NaHCO3
NaOAc
Na2CO3
NaOH
K3PO4
K2CO3
DIPEA
KOH
DCE (0.5)
40
40
40
40
40
40
40
40
40
40
25
70
70
70
70
70
50
70
70
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.1
1.2
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
6
6
–
c
DCE (0.5)
–
c
3
DCE (0.5)
–
c
4
DCE (0.5)
–
c
5
DCE (0.5)
–
c
6
DCE (0.5)
–
c
7
DCE (0.5)
–
8
DCE (0.5)
11
10
7
9
t-BuOK
Cs2CO3
KOH
DCE (0.5)
10
11
12
13
14
15
16
17
18
19
DCE (0.5)
CH2Cl2 (0.5)
EtOAc (0.5)
DCE (0.5)
trace
4
KOH
KOH
17
99
98
92
93
89
97
KOH
CH3CN (0.5)
CH3CN (0.3)
CH3CN (0.8)
CH3CN (0.5)
CH3CN (0.5)
CH3CN (0.5)
KOH
KOH
KOH
KOH
KOH
a Reaction conditions: 7-tosyl-7-azabicyclo[4.1.0]heptane (1a; 0.1 mmol),
benzaldehyde oxime (2a; 0.12 mmol), base catalyst (10 mol%).
b Isolated yield.
c Not detected.
tained in good to excellent yields. It is noteworthy that ste-
ric hindrance of the substituents on the aromatic ring of ar-
omatic aldoximes has an obvious influence on the yield and
reactivity, and the meta- and para-substituted aromatic al-
doximes afford higher yields than the ortho-substituted
ones (3c, 3d vs. 3b, and 3f, 3g vs. 3e, and 3i, 3j vs. 3h, and 3l
vs. 3k). The electronic properties have no evident effect on
the yield, and aldoximes bearing electron-donating groups
such as MeO, Me, or electron-withdrawing groups such as
Cl, NO2 at any position of the phenyl ring exhibit similarly
high yields (3b–3l). Notably, relatively lower yields are ob-
tained for substrates having a strong electron-withdrawing
group NO2 under the standard conditions because some
other compounds were produced in the reaction process.
Finally, reduction of reaction temperature and extension of
reaction time were required to increase the yields (3k and
3l). Gratifyingly, heteroaromatic aldoximes such as pyri-
dine-2-, -3-, and -4-carbaldehyde oxime were also tolerat-
Having established the optimal reaction conditions, we
first investigated a wide range of aldoximes using 7-tosyl-7-
azabicyclo[4.1.0]heptane (1a), and the results are shown in
Scheme 1. The reactions worked very well with aromatic al-
doximes, and the corresponding products 3a–q were ob-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

C
X. Li et al.
Paper
Synthesis
O
N
OH
R
KOH (10 mol%)
CH3CN
N
N
Ts
+
R
NH
Ts
1a
2(a–t)
3(a–t)
OMe
O
N
O
N
OMe
O
N
O
N
O
N
O
N
OMe
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3a, 6 h, 97%
3b, 9 h, 90%
3c, 7 h, 91%
3d, 7 h, 92%
3e, 9 h, 92%
3f, 7 h, 95%
Cl
NO2
Cl
O
N
O
N
O
N
O
N
O
N
O
N
Cl
NO2
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3j, 7 h, 94%
3k, 10 h, 82%a, b
trans/cis = 97:3
3l, 10 h, 92%a, b
trans/cis = 94:6
3g, 7 h, 97%
3i, 7 h, 90%
3h, 9 h, 83%
N
O
N
O
N
O
N
N
O
N
N
O
N
O
N
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3p, 7 h, 79%a
trans/cis = 91:9
O
3n, 7 h, 95%
3o, 9 h, 74%
3m, 7 h, 88%
3q, 7 h, 96%
3r, 7 h, 98%
O
N
N
NH
Ts
NH
Ts
3t, 45 h, 30%
3s, 45 h, 27%
Scheme 1 Reactions of 7-tosyl-7-azabicyclo[4.1.0]heptane (1a) with a variety of aldoximes. Reagents and conditions: 7-tosyl-7-azabicyclo[4.1.0]hep-
tane (1a; 0.1 mmol), aldoxime 2 (0.12 mmol), KOH (10 mol%), CH3CN (0.5 mL), 70 °C; isolated yields are given. a 25 °C was used. b Two isomers cannot
be separated and the yield was calculated based on selectivity which were determined by 1H NMR.
ed, affording the desired products 3m, 3n, and 3o in 88%,
95%, and 74% yields, respectively. Additionally, the sterically
hindered 1-naphthaldehyde oxime and 2-naphthaldehyde
oxime reacted smoothly to provide the desired products 3p
and 3q in 79% and 96% yields, respectively. Notably, cin-
namaldehyde oxime showed very high reactivity and yield,
which may be due to the effect of the double bond of conju-
gated structure 3r. Unfortunately, with regard to aliphatic
aldoximes, lower yields were obtained and longer reaction
times were required due to their low reactivity (3s and 3t).
Then, we explored the reactions of various N-tosylaziri-
dines with benzaldehyde oxime (2a) to better understand
the generality of this method (Scheme 2). In contrast to ali-
phatic N-tosylaziridine 1a, relatively lower yields for major
products were observed regarding aromatic N-tosylaziri-
dines using KOH as the catalyst; Cs2CO3, t-BuOK, and DIPEA
also did not give good results. This is due to lower reaction
reactivity and the formation of various isomers that were
produced from different selectivities in the reaction pro-
cess. Excitedly, when Et3N was utilized as the catalyst, 2-
phenyl-1-tosylaziridine gave 4b in 68% yield and 2-phenyl-
1-tosylaziridines substituted by an electron-donating group
gave modest yields of products 4c–e containing another
isomer 5. 2-Phenyl-1-tosylaziridine bearing an electron-
withdrawing group with K2CO3 as the catalyst gave 4f–h in
42–50% yields, which were higher yields than those ob-
tained using Et3N. It was found that naphthaldehyde-de-
rived N-tosylaziridines could also participate in the reac-
tion, albeit giving 4i and 4j in lower yields with longer reac-
tion times. Furthermore, diverse aliphatic N-tosylaziridines
were explored under the optimum reaction conditions and
only a single regioisomer was attained (5k–n). Cyclic ali-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

D
X. Li et al.
Paper
Synthesis
O
N
O
N
Et3N (10 mol%)
CHCl3
R2
R3
Ph
R2
R3
R2
Ph
OH
N
N
Ts
+
+
or
R3
Ph
NH
NH
KOH (10 mol%)
CH3CN
Ts
Ts
1(b–n)
4(b–k)
2a
5(b–n)
O
N
O
O
N
O
N
O
N
N
Cl
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
4f, 100 h, 46%b
4f:5f = 85:15
4b, 60 h, 68%a
4b:5b = 89:11
Cl
4e, 40 h, 58%
4e:5e = 83:17
4c, 40 h, 51%
4c:5c = 84:16
4d, 40 h, 51%
4d:5d = 77:23
Cl
O
N
O
N
O
N
O
N
O
N
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
4g, 100 h, 50%b
4g:5g = 73:27
4h, 90 h, 42%b
4h:5h = 76:24
4i, 96 h, 26%b
4i:5i = 70:30
5k, 7 h, 83%c
4j, 96 h, 19%b
4j:5j = 69:31
O
N
O
N
O
N
HO
NH
NH
NH
Ts
5
15
Ts
Ts
5l, 16 h, 69%c
5m, 16 h, 73%c
5n, 16 h, 46%c
Scheme 2 Reactions of a variety of N-tosylaziridines with benzaldehyde oxime (2a). Reagents and conditions: N-tosylaziridines 1 (0.1 mmol), benzalde-
hyde oxime (2a; 0.12 mmol), Et3N (10 mol%), CH3CN (0.5 mL), 60 °C; isolated yields are given. The products 5 were obtained when N-tosylaziridines
were attacked at the terminal position by benzaldehyde oxime and the ratios of two isomers were determined by mass ratio of separated products.
a 40 °C was used. b K2CO3 (10 mol%) was utilized as a catalyst. c KOH (10 mol%) and CH3CN (0.5 mL) were used at 70 °C.
phatic N-tosylaziridines had higher reactivity and gave
higher yields than chain-like ones, which provided moder-
ate yields (5k vs. 5l–n).
cally hindered 1-acetonaphthone and 2-acetonaphthone
oximes were also suitable substrates, providing the desired
products 3k′ and 3l′ in high yields. 2-Acetylfuran oxime and
2-acetylthiophene oxime gave 3m′ and 3n′ in 82% and 93%
yield, respectively. Aliphatic ketoximes have far lower reac-
tion activity and yields than aromatic ones (3o′–q′).
We next investigated the scope of N-tosylaziridines with
acetophenone oxime (2a′) (Scheme 4). Most substrates in-
dicated only moderate yields owing to the formation of di-
verse isomers in the reaction process. In terms of aromatic
N-tosylaziridines, the electronic properties and steric hin-
drance of substituents on the aromatic ring had no evident
effect on the yield and regioselectivity. All examined sub-
strates indicated moderate total yields and good regioselec-
tivities (4b′–4h′). In contrast to aliphatic chainlike N-tosyla-
ziridines, much higher yield was attained for cyclic aliphatic
ones (5i′ vs. 5j′).
To further demonstrate the generality of this method,
we applied it to the reaction of various ketoximes with 7-
tosyl-7-azabicyclo[4.1.0]heptane (1a) (Scheme 3). To our
delight, oximes derived from acetophenone and propiophe-
none were very compatible with the reaction conditions
and afforded the desired products 3a′ and 3b′ in 99% yields,
respectively. Ketoximes having an electron-donating or -
withdrawing group at the ortho, meta, and para position of
the phenyl ring could be smoothly converted into the corre-
sponding products 3c′–3j′ in good to high yields. Notably,
electron-donating (Me) and weak electron-withdrawing
group (Cl) gave higher yields than strong electron-with-
drawing groups (3c′–3g′ vs. 3h′–3j′), and the strong elec-
tron-withdrawing group NO2 exhibited higher reaction re-
activity under the same reaction conditions which led to
some other products. Excitedly, the yields for substrates
containing a strong electron-withdrawing functional group
NO2 could be improved by lowering the reaction tempera-
ture and prolonging the reaction time (3h′–3j′). The steri-
To demonstrate the synthetic potential of this devel-
oped protocol, two selected reactions were performed on a
2.5-mmol scale of starting materials. As shown in Scheme
5, in the presence of 10 mol% KOH, product 3a (0.87 g, 93%)
was obtained via the reaction of 2.5 mmol of 7-tosyl-7-aza-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

E
X. Li et al.
Paper
Synthesis
O
N
OH
R1
R
KOH (10 mol%)
CH3CN
N
N
Ts
+
R1
NH
Ts
R
1a
2(a–q)'
3(a–q)'
Cl
O
N
O
N
O
N
O
N
O
N
O
N
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3f', 8 h, 95%
3d', 10 h, 90%
3e', 9 h, 97%
3b', 8 h, 99%
3c', 10 h, 83%
3a', 8 h, 99%
O
N
Br
NO2
O
N
O
N
O
N
O
N
O
N
NO2
NH
Ts
NO2
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3j', 15 h, 76%a
3i', 15 h, 81%a
3h', 15 h, 75%a
3k', 8 h, 94%
3l', 10 h, 99%
3g', 8 h, 99%
O
O
N
S
O
O
O
N
O
N
N
N
NH
Ts
NH
Ts
NH
Ts
NH
Ts
NH
Ts
3m', 15 h, 82%
3q', 40 h, 47%
3n', 10 h, 93%
3o', 40 h, 38%
3p', 40 h, 32%
Scheme 3 Reactions of 7-tosyl-7-azabicyclo[4.1.0]heptane (1a) with a variety of ketoximes. Reagents and conditions: 7-tosyl-7-azabicyclo[4.1.0]hep-
tane (1a; 0.1 mmol ), ketoxime 2′ (0.12 mmol), KOH (10 mol%), CH3CN (0.5 mL), 70 °C; isolated yields are given. a 25 °C was used.
O
N
O
N
R2
R3
R2
R3
Ph
OH
R2
R3
Ph
KOH (10 mol%)
CH3CN
N
N
Ts
+
+
Ph
NH
NH
Ts
Ts
1(b–j)
4(b–h)'
2a'
5(i–j)'
Cl
OMe
O
N
O
N
O
N
O
N
O
N
NH
Ts
NH
NH
Ts
NH
Ts
NH
Ts
Ts
4b', 8 h, 58%
4b':5b' = 84:16
4c', 8 h, 66%
4c':5c' = 88:12
4d', 7 h, 58%
4d':5d' = 76:24
4e', 9 h, 63%
4e':5e' = 71:29
4f', 10 h, 54%
4f':5f' = 87:13
Cl
O
O
N
O
O
N
N
N
NH
Ts
NH
Ts
NH
Ts
5
NH
Ts
5j', 10 h, 54%
4g', 9 h, 78%
4g':5g' = 85:15
5i', 10 h, 94%
4h', 8 h, 91%
4h':5h' = 75:25
Scheme 4 Reactions of a variety of N-tosylaziridines with acetophenone oxime. Reagents and conditions: N-tosylaziridine 1 (0.1 mmol ), acetophenone
oxime (2a′; 0.12 mmol), KOH (10 mol%), CH3CN (0.5 mL), 70 °C; isolated yield are given. The products 5′ were obtained when N-tosylaziridines were
attacked at the terminal position by acetophenone oxime, and the ratios of isomers were determined by 1H NMR.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

F
X. Li et al.
Paper
Synthesis
bicyclo[4.1.0]heptane (1a) with 1.2 equiv of benzaldehyde
oxime (2a) (Scheme 5). In addition, the reaction of 2.5
mmol of 1a with 1.2 equiv of 2a′ gave 3a′ (0.93 g) in 97%
yield (Scheme 5).
into intermediate B. Second, it undergoes the N-ring-open-
ing reaction to 7-tosyl-7-azabicyclo[4.1.0]heptane (1a) to
afford the desired product 3 or 3′. During the course of this
reaction, O-ring-opening products 6 were not detected for
most substrates.
O
OH
R1
R2
N
N
KOH (10 mol%)
N
Ts
+
CH3CN (10 mL)
70 °C, 7 h
N
NH
N-attack
O
Ts
N
Ts
NHTs
HO
O
O
1a
2a
3a (93% yield)
3 or 3'
N
N
N
KOH
1a
R2
O
N
R1 R2
R1 R2
R1 R2
OH
R1
N
KOH (10 mol%)
2
A
B
N
O
O-attack
N
Ts
+
CH3CN (10 mL)
70 °C, 9 h
not found
NH
Ts
NHTs
1a
2a'
3a' (97% yield)
6
Scheme 5 2.5-mmol-scale version
Scheme 7 Reaction mechanism
In order to verify the transformation of (E)-benzalde-
hyde oxime to (Z)-benzaldehyde oxime in the reaction pro-
cess, two control experiments were carried out under stan-
dard conditions (Scheme 6). Only 96% yield of product 3a
was obtained when 7-tosyl-7-azabicyclo[4.1.0]heptane (1a)
was reacted with a mixture of benzaldehyde oxime (E/Z
1:1) (Scheme 6); 0.06 mmol of (Z)-benzaldehyde oxime
would be produced if 0.1 mmol of (E)-benzaldehyde oxime
was treated for 6 h. These two results indicated that (E)-
benzaldehyde oxime could be smoothly converted into (Z)-
benzaldehyde oxime (Scheme 6).
In conclusion, we have developed a KOH-, K2CO3-, or
Et3N-catalyzed ring-opening reaction of N-tosylaziridines
using nitrogen atom of a series of (E)-aldoximes and (E)-ke-
toximes as a nucleophilic atom instead of oxygen atom to
construct the diverse nitrones under mild reaction condi-
tions. The attractive advantages of this method include em-
ploying easily available, relatively inexpensive KOH, K2CO3,
or Et3N as a catalyst, wide substrate scope, experimental
ease of operation, and low catalyst loading.
HO
N
1H NMR spectra were taken on a Bruker Avance III 600 MHz NMR
spectrometers and referenced to the CDCl3 resonance ( = 7.27). 13C
NMR data were collected at 150 MHz with complete proton decou-
pling and referenced to the central CDCl3 resonance ( = 77.0). HRMS
were performed on a micrOTOF-Q II instrument with an ESI source.
Melting points were measured with a RD-II melting point apparatus
and are uncorrected. Unless otherwise noted, reagents obtained from
commercial sources were used without further purification. All sol-
vents were purchased from commercial sources and used with fur-
ther purification. Deuterated solvents were purchased from Sigma-
Aldrich. Column chromatography was performed on silica gel (200–
300 mesh). All yields were referred to isolated yields (average of two
runs) of compounds.
O
N
KOH (10 mol%)
0.06 mmol
N
Ts
+
OH
CH3CN (0.5 mL)
70 °C, 6 h
NH
Ts
N
1a
0.1 mmol
3a
96% yield
2a
0.06 mmol
(E)-benzaldehyde oxime
HO
N
OH
OH
N
N
Nitrones; General Procedure
KOH (10 mol%)
+
A mixture of N-tosylaziridine 1 (0.1 mmol) and oxime 2 or 2′ (0.12
mmol) in CH3CN (0.5 mL) in the presence of KOH (10 mol%) as a cata-
lyst was stirred at the specified temperature until the substrate had
been completely consumed as determined by TLC. Subsequently, the
mixture was purified by column chromatography (silica gel, EtOAc/
PE) to afford the product.
CH3CN (0.5 mL)
70 °C, 6 h
1a
0.1 mmol
0.04 mmol
0.06 mmol
Scheme 6 Control experiments
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-phenylmeth-
animine Oxide (3a)
On the basis of the literature studies, a mechanism is
provided in Scheme 7 to rationalize this process.20 First, the
intermediate A is generated from substrate 2 or 2′ in the
presence of KOH as a catalyst, which could be converted
White solid; yield: 36.1 mg (97%, 0.1 mmol scale); 0.87 g (93%, 2.5
mmol scale); mp 106–107 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

G
X. Li et al.
Paper
Synthesis
1H NMR (600 MHz, CDCl3):  = 7.65 (d, J = 8.2 Hz, 2 H), 7.60 (s, 1 H),
7.42–7.44 (m, 2 H), 7.35–7.39 (m, 3 H), 7.10 (d, J = 8.1 Hz, 2 H), 5.26
(d, J = 4.0 Hz, 1 H), 3.83–3.88 (m, 1 H), 3.15–3.20 (m, 1 H), 2.30–2.33
(m, 1 H), 2.30 (s, 3 H), 2.02–2.06 (m, 1 H), 1.71–1.74 (m, 1 H), 1.64–
1.67 (m, 1 H), 1.30–1.41 (m, 2 H), 1.19–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 151.6, 145.8, 140.5, 134.7, 133.0,
132.2, 131.7, 130.1, 129.8, 86.1, 60.1, 36.0, 33.5, 26.8, 26.8, 24.3.
1H NMR (600 MHz, CDCl3):  = 7.93 (s, 1 H), 7.66 (d, J = 8.2 Hz, 2 H),
7.51 (d, J = 7.5 Hz, 1 H), 7.26–7.29 (m, 1 H), 7.17 (q, J = 7.3 Hz, 2 H),
7.09 (d, J = 8.0 Hz, 2 H), 5.31 (d, J = 3.8 Hz, 1 H), 3.85–3.90 (m, 1 H),
3.17–3.22 (m, 1 H), 2.34 (s, 3 H), 2.30–2.33 (m, 1 H), 2.28 (s, 3 H),
2.04–2.07 (m, 1 H), 1.71–1.74 (m, 1 H), 1.64–1.67 (m, 1 H), 1.31–1.41
(m, 2 H), 1.24–1.30 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 150.8, 145.8, 140.4, 139.6, 133.8,
132.8, 132.7, 132.2, 130.1, 129.9, 129.1, 85.9, 60.1, 35.9, 33.5, 26.9,
26.8, 24.3, 22.9.
HRMS (ESI): m/z [M + H] calcd for C20H25N2O3S: 373.1586; found:
373.1565.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O3S: 387.1742; found:
387.1738.
1-(2-Methoxyphenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}methanimine Oxide (3b)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(m-
tolyl)methanimine Oxide (3f)
White solid; yield: 36.0 mg (90%); mp 169–170 °C.
1H NMR (600 MHz, CDCl3):  = 8.05 (s, 1 H), 7.65 (d, J = 8.1 Hz, 2 H),
7.57 (q, J = 1.6 Hz, 1 H), 7.34–7.37 (m, 1 H), 7.11 (d, J = 8.1 Hz, 2 H),
6.93 (t, J = 7.4 Hz, 1 H), 6.90 (d, J = 8.3 Hz, 1 H), 5.48 (d, J = 3.9 Hz, 1 H),
3.84–3.89 (m, 4 H), 3.09–3.14 (m, 1 H), 2.32–2.35 (m, 1 H), 2.30 (s, 3
H), 2.02–2.05 (m, 1 H), 1.70–1.73 (m, 1 H), 1.64–1.66 (m, 1 H), 1.30–
1.39 (m, 2 H), 1.19–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 160.4, 148.0, 145.8, 140.2, 134.3,
132.2, 130.1, 129.5, 123.7, 114.0, 85.8, 60.5, 58.5, 36.0, 33.5, 26.9,
26.8, 24.3.
White solid; yield: 36.7 mg (95%); mp 98–99 °C.
1H NMR (600 MHz, CDCl3):  = 7.66 (d, J = 8.0 Hz, 2 H), 7.57 (s, 1 H),
7.26 (d, J = 4.7 Hz, 2 H), 7.18 (q, J = 7.6 Hz, 2 H), 7.11 (d, J = 8.5 Hz, 2 H),
5.30 (d, J = 4.4 Hz, 1 H), 3.84–3.88 (m, 1 H), 3.15–3.20 (m, 1 H), 2.37 (s,
3 H), 2.32–2.34 (m, 1 H), 2.30 (s, 3 H), 2.03–2.06 (m, 1 H), 1.71–1.74
(m, 1 H), 1.64–1.67 (m, 1 H), 1.30–1.40 (m, 2 H), 1.22–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 151.8, 145.8, 141.4, 140.5, 134.6,
133.8, 132.2, 131.5, 130.2, 130.1, 127.2, 86.0, 60.1, 36.0, 33.5, 26.9,
26.8, 24.3, 24.2.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O4S: 403.1692; found:
403.1685.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O3S: 387.1742; found:
387.1739.
1-(3-Methoxyphenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}methanimine Oxide (3c)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(p-tolyl)meth-
animine Oxide (3g)
White solid; yield: 37.1 mg (91%); mp 101–102 °C.
White solid; yield: 37.0 mg (97%); mp 123–124 °C.
1H NMR (600 MHz, CDCl3):  = 7.66 (d, J = 8.2 Hz, 2 H), 7.58 (s, 1 H),
7.27 (t, J = 8.0 Hz, 1 H), 7.12 (d, J = 8.4 Hz, 2 H), 7.01–7.02 (m, 1 H),
6.97 (d, J = 7.9 Hz, 1 H), 6.92 (qd, J = 1.0, 0.8 Hz, 1 H), 5.32 (d, J = 4.8 Hz,
1 H), 3.85–3.89 (m, 1 H), 3.84 (s, 3 H), 3.15–3.20 (m, 1 H), 2.29–2.33
(m, 4 H), 2.03–2.06 (m, 1 H), 1.71–1.74 (m, 1 H), 1.64–1.67 (m, 1 H),
1.31–1.41 (m, 2 H), 1.24–1.30 (m, 2 H).
1H NMR (600 MHz, CDCl3):  = 7.65 (d, J = 8.5 Hz, 2 H), 7.58 (s, 1 H),
7.32 (d, J = 8.2 Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H), 7.10 (d, J = 7.7 Hz, 2 H),
5.36 (d, J = 4.0 Hz, 1 H), 3.83–3.87 (m, 1 H), 3.13–3.18 (m, 1 H), 2.37 (s,
3 H), 2.31–2.34 (m, 1 H), 2.30 (s, 3 H), 2.03–2.05 (m, 1 H), 1.70–1.74
(m, 1 H), 1.64–1.66 (m, 1 H), 1.30–1.39 (m, 2 H), 1.21–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 162.8, 151.6, 145.8, 140.6, 132.6,
132.2, 130.1, 122.9, 119.1, 114.2, 86.1, 60.0, 58.2, 35.8, 33.5, 29.8,
26.8, 24.3.
13C NMR (150 MHz, CDCl3):  = 151.7, 145.8, 143.2, 140.4, 132.4,
132.2, 131.9, 130.1, 129.8, 85.9, 60.3, 36.0, 33.5, 26.9, 26.8, 24.4, 24.3.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O3S: 387.1742; found:
HRMS (ESI): m/z [M + H] calcd for C21H27N2O4S: 403.1692; found:
387.1731.
403.1685.
1-(2-Chlorophenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
1-(4-Methoxyphenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}methanimine Oxide (3h)
hexyl}methanimine Oxide (3d)
White solid; yield: 32.6 mg (83%); mp 129–130 °C.
White solid; yield: 37.2 mg (92%); mp 134–135 °C.
1H NMR (600 MHz, CDCl3):  = 8.03 (s, 1 H), 7.70 (q, J = 1.7 Hz, 1 H),
7.66 (d, J = 8.3 Hz, 2 H), 7.36 (q, J = 1.2 Hz, 1 H), 7.29 (td, J = 1.7, 1.7, 1.7
Hz, 1 H), 7.23–7.25 (m, 1 H), 7.12 (d, J = 8.0 Hz, 2 H), 5.18 (d, J = 4.6 Hz,
1 H), 3.86–3.91 (m, 1 H), 3.18–3.23 (m, 1 H), 2.31–2.34 (m, 1 H), 2.28
(s, 3 H), 2.04–2.07 (m, 1 H), 1.71–1.75 (m, 1 H), 1.65–1.68 (m, 1 H),
1.32–1.43 (m, 2 H), 1.24–1.29 (m, 2 H).
1H NMR (600 MHz, CDCl3):  = 7.65 (d, J = 8.2 Hz, 2 H), 7.58 (s, 1 H),
7.37 (dt, J = 2.6, 2.0 Hz, 2 H), 7.12 (d, J = 7.9 Hz, 2 H), 6.88 (dt, J = 2.9,
1.8 Hz, 2 H), 5.40 (d, J = 4.1 Hz, 1 H), 3.82–3.86 (m, 4 H), 3.12–3.18 (m,
1 H), 2.29–2.33 (m, 4 H), 2.01–2.06 (m, 1 H), 1.71–1.74 (m, 1 H), 1.63–
1.66 (m, 1 H), 1.30–1.39 (m, 2 H), 1.21–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 164.1, 151.3, 145.7, 140.6, 132.2,
131.3, 130.1, 127.4, 117.2, 85.7, 60.3, 58.2, 35.8, 33.5, 26.9, 26.8, 24.3.
13C NMR (150 MHz, CDCl3):  = 148.5, 146.0, 140.3, 136.6, 133.9,
132.8, 132.4, 132.3, 130.0, 129.9, 129.8, 86.5, 59.9, 36.2, 33.6, 26.9,
26.8, 24.4.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O4S: 403.1692; found:
403.1680.
HRMS (ESI): m/z [M + H] calcd for C20H24ClN2O3S: 407.1196; found:
407.1190.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(o-tolyl)meth-
animine Oxide (3e)
1-(3-Chlorophenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}methanimine Oxide (3i)
White solid; yield: 35.6 mg (92%); mp 109–110 °C.
White solid; yield: 35.5 mg (90%); mp 109–110 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

H
X. Li et al.
Paper
Synthesis
1H NMR (600 MHz, CDCl3):  = 7.67 (d, J = 8.2 Hz, 2 H), 7.55 (s, 1 H),
7.41 (s, 1 H), 7.33 (dt, J = 2.6, 2.3 Hz, 1 H), 7.27–7.31 (m, 2 H), 7.12 (d,
J = 8.2 Hz, 2 H), 5.11 (d, J = 4.7 Hz, 1 H), 3.83–3.88 (m, 1 H), 3.21–3.27
(m, 1 H), 2.30 (s, 3 H), 2.27–2.28 (m, 1 H), 2.03–2.05 (m, 1 H), 1.71–
1.74 (m, 1 H), 1.64–1.67 (m, 1 H), 1.31–1.45 (m, 2 H), 1.25–1.28 (m, 2
H).
13C NMR (150 MHz, CDCl3):  = 154.2, 152.6, 152.3, 146.0, 140.4,
139.4, 132.7, 132.3, 130.0, 127.0, 123.7, 86.8, 59.7, 36.1, 33.6, 26.8,
26.7, 24.4.
HRMS (ESI): m/z [M + H] calcd for C19H24N3O3S: 374.1538; found:
374.1532.
13C NMR (150 MHz, CDCl3):  = 150.2, 145.9, 140.6, 137.7, 136.6,
132.9, 132.3, 130.0, 129.5, 128.1, 86.5, 59.5, 35.9, 33.5, 26.8, 26.7,
24.3.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(pyridin-3-
yl)methanimine Oxide (3n)
White solid; yield: 34.2 mg (95%); mp 118–119 °C.
HRMS (ESI): m/z [M + H] calcd for C20H24ClN2O3S: 407.1196; found:
407.1190.
1H NMR (600 MHz, CDCl3):  = 8.60 (q, J = 1.6 Hz, 1 H), 8.56 (d, J = 1.7
Hz, 1 H), 7.80 (dt, J = 1.9, 1.9 Hz, 1 H), 7.68 (d, J = 8.3 Hz, 2 H), 7.60 (s, 1
H), 7.29 (q, J = 4.8 Hz, 1 H), 7.14 (d, J = 8.0 Hz, 2 H), 5.19 (d, J = 4.9 Hz,
1 H), 3.87–3.91 (m, 1 H), 3.23–3.29 (m, 1 H), 2.30 (s, 3 H), 2.27–2.28
(m, 1 H), 2.05–2.07 (m, 1 H), 1.71–1.75 (m, 1 H), 1.65–1.67 (m, 1 H),
1.33–1.45 (m, 2 H), 1.25–1.29 (m, 2 H).
1-(4-Chlorophenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}methanimine Oxide (3j)
White solid; yield: 37.0 mg (94%); mp 120–121 °C.
1H NMR (600 MHz, CDCl3):  = 7.66 (d, J = 8.2 Hz, 2 H), 7.58 (s, 1 H),
7.33 (q, J = 8.6 Hz, 4 H), 7.12 (d, J = 8.0 Hz, 2 H), 5.19 (d, J = 4.4 Hz, 1 H),
3.83–3.88 (m, 1 H), 3.19–3.24 (m, 1 H), 2.31 (s, 3 H), 2.26–2.29 (m, 1
H), 2.03–2.05 (m, 1 H), 1.71–1.74 (m, 1 H), 1.64–1.67 (m, 1 H), 1.30–
1.43 (m, 2 H), 1.23–1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 153.7, 151.6, 148.5, 145.8, 140.8,
136.1, 132.3, 130.9, 130.0, 126.6, 86.7, 59.5, 36.0, 33.5, 26.8, 26.7,
24.3.
HRMS (ESI): m/z [M + H] calcd for C19H24N3O3S: 374.1538; found:
374.1537.
13C NMR (150 MHz, CDCl3):  = 150.4, 145.8, 140.6, 138.8, 133.3,
132.3, 131.9, 130.9, 130.1, 86.3, 59.8, 35.9, 33.5, 26.8, 26.7, 24.3.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(pyridin-4-
yl)methanimine Oxide (3o)
HRMS (ESI): m/z [M + H] calcd for C20H24ClN2O3S: 407.1196; found:
407.1190.
White solid; yield: 26.7 mg (74%); mp 175–176 °C.
1H NMR (600 MHz, CDCl3):  = 8.62 (d, J = 6.0 Hz, 2 H), 7.67 (d, J = 8.2
Hz, 2 H), 7.56 (s, 1 H), 7.29 (q, J = 1.4 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H),
5.06 (d, J = 5.0 Hz, 1 H), 3.89–3.93 (m, 1 H), 3.26–3.30 (m, 1 H), 2.30 (s,
3 H), 2.25–2.27 (m, 1 H), 2.05–2.07 (m, 1 H), 1.73–1.76 (m, 1 H), 1.66–
1.68 (m, 1 H), 1.34–1.46 (m, 2 H), 1.28–1.33 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 153.2, 149.4, 145.8, 142.2, 140.9,
132.3, 130.0, 123.7, 87.0, 59.3, 35.9, 33.5, 26.8, 26.7, 24.3.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(2-nitrophe-
nyl)methanimine Oxide (3k)
Yellow solid; yield: 34.2 mg (82%); mp 108–110 °C.
1H NMR (600 MHz, CDCl3):  = 8.19 (s, 1 H), 8.01 (q, J = 1.1 Hz, 1 H),
7.85 (q, J = 1.3 Hz, 1 H), 7.69 (d, J = 8.3 Hz, 2 H), 7.61 (dt, J = 0.8, 0.5 Hz,
1 H), 7.52 (dt, J = 1.4, 1.2 Hz, 1 H), 7.17 (d, J = 8.0 Hz, 2 H), 5.14 (d, J =
5.0 Hz, 1 H), 3.91–3.95 (m, 1 H), 3.19–3.25 (m, 1 H), 2.31 (s, 3 H),
2.27–2.30 (m, 1 H), 2.06–2.09 (m, 1 H), 1.72–1.75 (m, 1 H), 1.65–1.67
(m, 1 H), 1.34–1.43 (m, 2 H), 1.25–1.30 (m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C19H24N3O3S: 374.1538; found:
374.1537.
HRMS (ESI): m/z [M + H] calcd for C20H24N3O5S: 418.1437; found:
418.1432.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(naphthalen-
1-yl)methanimine Oxide (3p)
White solid; yield: 33.4 mg (79%); mp 106–107 °C.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(3-nitrophe-
nyl)methanimine Oxide (3l)
1H NMR (600 MHz, CDCl3):  = 8.32 (d, J = 8.4 Hz, 1 H), 8.28 (s, 1 H),
7.89 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 8.2 Hz, 2 H), 7.63 (d, J = 7.0 Hz, 1 H),
7.56–7.59 (m, 1 H), 7.52–7.55 (m, 1 H), 7.47 (t, J = 7.9 Hz, 1 H), 7.00 (d,
J = 8.0 Hz, 2 H), 5.24 (d, J = 4.1 Hz, 1 H), 3.94–3.98 (m, 1 H), 3.24–3.30
(m, 1 H), 2.33–2.36 (m, 1 H), 2.12–2.14 (m, 4 H), 1.75–1.78 (m, 1 H),
1.67–1.70 (m, 1 H), 1.37–1.48 (m, 2 H), 1.26–1.31 (m, 2 H).
Yellowish solid; yield: 38.4 mg (92%); mp 101–102 °C.
1H NMR (600 MHz, CDCl3):  = 8.24 (d, J = 1.6 Hz, 1 H), 8.20–8.22 (m, 1
H), 7.76 (d, J = 7.7 Hz, 1 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.65 (t, J = 3.8 Hz, 1
H), 7.54 (t, J = 7.9 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 5.08 (d, J = 5.3 Hz, 1
H), 3.89–3.94 (m, 1 H), 3.27–3.33 (m, 1 H), 2.31 (s, 3 H), 2.21–2.24 (m,
1 H), 2.06–2.09 (m, 1 H), 1.73–1.75 (m, 1 H), 1.65–1.66 (m, 1 H), 1.40–
1.47 (m, 1 H), 1.32–1.35 (m, 1 H), 1.27–1.31 (m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C24H27N2O3S: 423.1742; found:
423.1732.
HRMS (ESI): m/z [M + H] calcd for C20H24N3O5S: 418.1437; found:
418.1432.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(naphthalen-
2-yl)methanimine Oxide (3q)
White solid; yield: 40.6 mg (96%); mp 129–132 °C.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(pyridin-2-
yl)methanimine Oxide (3m)
1H NMR (600 MHz, CDCl3):  = 7.84–7.87 (m, 2 H), 7.82 (d, J = 8.6 Hz, 1
H), 7.74 (s, 1 H), 7.72 (s, 1 H), 7.67 (dd, J = 1.7, 1.5 Hz, 1 H), 7.65 (d, J =
8.3 Hz, 2 H), 7.52–7.54 (m, 2 H), 7.08 (d, J = 8.1 Hz, 2 H), 5.28 (d, J = 3.8
Hz, 1 H), 3.89–3.93 (m, 1 H), 3.19–3.24 (m, 1 H), 2.34–2.37 (m, 1 H),
2.24 (s, 3 H), 2.07–2.10 (m, 1 H), 1.75–1.77 (m, 1 H), 1.67–1.69 (m, 1
H), 1.36–1.44 (m, 2 H), 1.25–1.32 (m, 2 H).
White solid; yield: 31.7 mg (88%); mp 140–141 °C.
1H NMR (600 MHz, CDCl3):  = 8.60 (dt, J = 0.8, 0.7 Hz, 1 H), 7.69–7.71
(m, 2 H), 7.66–7.68 (m, 2 H), 7.63 (d, J = 7.9 Hz, 1 H), 7.26–7.29 (m, 1
H), 7.13 (d, J = 8.3 Hz, 2 H), 5.14 (d, J = 5.6 Hz, 1 H), 3.91–3.95 (m, 1 H),
3.18–3.24 (m, 1 H), 2.31–2.33 (m, 1 H), 2.30 (s, 3 H), 2.05–2.08 (m, 1
H), 1.73–1.75 (m, 1 H), 1.65–1.67 (m, 1 H), 1.31–1.46 (m, 2 H), 1.23–
1.30 (m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C24H27N2O3S: 423.1742; found:
423.1730.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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Synthesis
(E)-N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-3-phenyl-
prop-2-en-1-imine Oxide (3r)
1H NMR (600 MHz, CDCl3):  = 7.86 (s, 1 H), 7.57 (d, J = 8.5 Hz, 2 H),
7.47 (dd, J = 2.1, 1.4 Hz, 2 H), 7.39–7.42 (m, 3 H), 7.27–7.30 (m, 4 H),
7.24–7.26 (m, 1 H), 7.04 (d, J = 8.2 Hz, 2 H), 5.42 (d, J = 4.3 Hz, 1 H),
4.61–4.65 (m, 1 H), 4.19 (q, J = 4.0 Hz, 1 H), 4.07 (q, J = 8.6 Hz, 1 H),
2.22 (s, 3 H).
Colorless liquid; yield: 37.7 mg (98%).
1H NMR (600 MHz, CDCl3):  = 7.71 (d, J = 8.4 Hz, 2 H), 7.44–7.45 (m, 2
H), 7.41 (d, J = 8.9 Hz, 1 H), 7.36 (td, J = 1.7, 1.2 Hz, 2 H), 7.31 (tt, J = 2.1,
1.2 Hz, 1 H), 7.23 (dd, J = 1.8, 0.6 Hz, 2 H), 6.66 (t, J = 6.8 Hz, 2 H), 5.18
(d, J = 4.0 Hz, 1 H), 3.77–3.81 (m, 1 H), 3.13–3.18 (m, 1 H), 2.37 (s, 3
H), 2.29–2.31 (m, 1 H), 2.01–2.05 (m, 1 H), 1.72–1.74 (m, 1 H), 1.63–
1.66 (m, 1 H), 1.32–1.36 (m, 2 H), 1.28–1.31 (m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C22H23N2O3S: 395.1429; found:
395.1423.
N-{2-[(4-Methylphenyl)sulfonamido]-1-(o-tolyl)ethyl}-1-phenyl-
methanimine Oxide (4c)
13C NMR (150 MHz, CDCl3):  = 153.6, 145.8, 141.6, 140.7, 138.7,
132.3, 131.9, 131.8, 130.1, 129.8, 124.5, 86.2, 60.1, 35.9, 33.5, 29.8,
26.8, 26.8, 24.4.
White solid; yield: 20.8 mg (51%); mp 133–134 °C.
1H NMR (600 MHz, CDCl3):  = 8.05 (s, 1 H), 7.73 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 2.0, 1.5 Hz, 2 H), 7.33–7.37 (m, 3 H), 7.24 (d, J = 8.3 Hz, 3
H), 7.16 (dd, J = 2.3, 1.7 Hz, 1 H), 7.12–7.15 (m, 2 H), 5.45 (q, J = 3.5 Hz,
1 H), 5.13 (q, J = 3.6 Hz, 1 H), 3.39–3.44 (m, 1 H), 3.28–3.32 (m, 1 H),
2.38 (s, 3 H), 2.30 (s, 3 H).
13C NMR (150 MHz, CDCl3):  = 152.8, 146.3, 140.0, 139.3, 138.3,
134.6, 133.6, 133.1, 132.6, 131.6, 131.0, 130.1, 130.1, 129.1, 129.0,
83.2, 50.0, 24.4, 22.0.
HRMS (ESI): m/z [M + H] calcd for C22H27N2O3S: 399.1742; found:
399.1735.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}pentan-1-imine
Oxide (3s)
Colorless liquid; yield: 9.5 mg (27%).
1H NMR (600 MHz, CDCl3):  = 7.70 (d, J = 8.3 Hz, 2 H), 7.23 (d, J = 8.0
Hz, 2 H), 6.48 (t, J = 5.3 Hz, 1 H), 5.36 (d, J = 2.7 Hz, 1 H), 3.74–3.79 (m,
1 H), 3.02–3.06 (m, 1 H), 2.40 (s, 3 H), 2.24–2.27 (m, 1 H), 2.07–2.13
(m, 1 H), 1.90–1.97 (m, 2 H), 1.66–1.68 (m, 1 H), 1.60–1.61 (m, 1 H),
1.31–1.37 (m, 2 H), 1.23–1.30 (m, 4 H), 1.15–1.22 (m, 2 H), 0.87 (t, J =
7.3 Hz, 3 H).
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
409.1583.
N-{2-[(4-Methylphenyl)sulfonamido]-1-(m-tolyl)ethyl}-1-phenyl-
methanimine Oxide (4d)
Colorless liquid; yield: 20.8 mg (51%).
HRMS (ESI): m/z [M + H] calcd for C22H29N2O3S: 353.1899; found:
1H NMR (600 MHz, CDCl3):  = 8.05 (s, 1 H), 7.71 (d, J = 8.3 Hz, 2 H),
7.48 (dd, J = 2.0, 1.5 Hz, 2 H), 7.33–7.37 (m, 3 H), 7.24 (d, J = 8.0 Hz, 2
H), 7.19 (t, J = 7.9 Hz, 1 H), 7.09 (d, J = 7.6 Hz, 1 H), 7.04–7.05 (m, 2 H),
5.17 (q, J = 4.1 Hz, 1 H), 4.96 (q, J = 4.2 Hz, 1 H), 3.42–3.46 (m, 1 H),
3.34–3.39 (m, 1 H), 2.39 (s, 3 H), 2.32 (s, 3 H).
353.1898.
3-Methyl-N-{2-[(4-methylphenyl)sulfonamido]cyclohexyl}butan-
1-imine Oxide (3t)
Colorless liquid; yield: 8.0 mg (30%).
13C NMR (150 MHz, CDCl3):  = 152.9, 146.3, 141.2, 141.0, 140.0,
134.6, 133.1, 132.6, 132.0, 131.6, 131.4, 130.2, 130.1, 130.1, 126.6,
86.1, 50.9, 24.4, 24.3.
1H NMR (600 MHz, CDCl3):  = 7.72 (d, J = 8.3 Hz, 2 H), 7.26 (d, J = 7.9
Hz, 2 H), 7.04 (t, J = 6.6 Hz, 1 H), 5.27 (d, J = 3.5 Hz, 1 H), 3.71–3.76 (m,
1 H), 3.04–3.10 (m, 1 H), 2.42 (s, 3 H), 2.22–2.25 (m, 1 H), 1.99–2.02
(m, 1 H), 1.96–1.98 (m, 2 H), 1.72–1.79 (m, 1 H), 1.68–1.69 (m, 1 H),
1.59–1.62 (m, 1 H), 1.25–1.30 (m, 2 H), 1.18–1.24 (m, 2 H), 0.91 (t, J =
6.4 Hz, 6 H).
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
409.1584.
13C NMR (150 MHz, CDCl3):  = 153.6, 145.8, 140.7, 132.3, 130.1, 85.2,
(Z)-N-Benzylidene-2-[(4-methylphenyl)sulfonamido)]-2-(m-
60.2, 41.1, 35.5, 33.5, 29.6, 26.8, 25.3, 25.2, 24.4.
tolyl)ethanamine Oxide (5d)
Colorless liquid; yield: 6.1 mg (15%).
HRMS (ESI): m/z [M + H] calcd for C18H29N2O3S: 353.1899; found:
1H NMR (600 MHz, CDCl3):  = 7.86 (s, 1 H), 7.56 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 2.2, 1.6 Hz, 2 H), 7.38–7.42 (m, 3 H), 7.15 (t, J = 7.5 Hz, 1
H), 7.08 (t, J = 8.0 Hz, 1 H), 7.03–7.05 (m, 4 H), 5.39 (d, J = 4.1 Hz, 1 H),
4.58–4.62 (m, 1 H), 4.17 (q, J = 4.1, 4.1 Hz, 1 H), 4.05 (q, J = 8.8 Hz, 1 H),
2.26 (s, 3 H), 2.21 (s, 3 H).
353.1899.
N-{2-[(4-Methylphenyl)sulfonamido]-1-phenylethyl}-1-phenyl-
methanimine Oxide (4b)
White solid; yield: 26.8 mg (68%); mp 110–111 °C.
1H NMR (600 MHz, CDCl3):  = 8.06 (s, 1 H), 7.71 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 1.9, 1.4 Hz, 2 H), 7.33–7.36 (m, 3 H), 7.31 (dt, J = 1.6, 1.4
Hz, 2 H), 7.28–7.30 (m, 1 H), 7.26 (d, J = 1.8 Hz, 2 H), 7.25 (s, 2 H), 5.20
(q, J = 4.1 Hz, 1 H), 4.95 (q, J = 4.1 Hz, 1 H), 3.43–3.48 (m, 1 H), 3.36–
3.41 (m, 1 H), 2.38 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
409.1584.
N-{2-[(4-Methylphenyl)sulfonamido]-1-(p-tolyl)ethyl}-1-phenyl-
methanimine Oxide (4e)
13C NMR (150 MHz, CDCl3):  = 152.9, 146.3, 141.2, 139.9, 134.6,
White solid; yield: 23.7 mg (58%); mp 119–120 °C.
1H NMR (600 MHz, CDCl3):  = 8.03 (s, 1 H), 7.71 (d, J = 8.3 Hz, 2 H),
7.46 (dd, J = 1.9, 1.4 Hz, 2 H), 7.32–7.36 (m, 3 H), 7.24 (d, J = 7.9 Hz, 2
H), 7.11–7.15 (m, 4 H), 5.17 (q, J = 4.2 Hz, 1 H), 5.00 (q, J = 4.3 Hz, 1 H),
3.40–3.45 (m, 1 H), 3.34–3.39 (m, 1 H), 2.38 (s, 3 H), 2.31 (s, 3 H).
133.1, 132.6, 131.6, 131.5, 131.2, 130.1, 130.0, 129.5, 86.1, 50.8, 24.4.
HRMS (ESI): m/z [M + H] calcd for C22H23N2O3S: 395.1429; found:
395.1423.
(Z)-N-Benzylidene-2-[(4-methylphenyl)sulfonamido]-2-pheny-
lethanamine Oxide (5b)
13C NMR (150 MHz, CDCl3):  = 152.8, 146.3, 141.1, 139.9, 138.1,
134.6, 133.1, 132.6, 132.2, 131.6, 130.1, 130.1, 129.5, 85.9, 50.8, 24.4,
24.1.
White solid; yield: 3.2 mg (8%); mp 127–129 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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Synthesis
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
409.1584.
1H NMR (400 MHz, CDCl3):  = 7.88 (s, 1 H), 7.75–7.68 (m, 1 H), 7.58–
7.51 (m, 3 H), 7.50 (dd, J = 7.2, 2.0 Hz, 2 H), 7.42–7.35 (m, 3 H), 7.21 (d,
J = 2.4 Hz, 2 H), 7.07 (d, J = 8.0 Hz, 2 H), 5.5 (d, J = 4.0 Hz, 1 H), 4.64–
4.58 (m, 1 H), 4.19 (dd, J = 8.4, 4.0 Hz, 1 H), 4.07 (dd, J = 3.6, 8.4 Hz, 1
H), 2.21 (s, 3 H).
(Z)-N-Benzylidene-2-[(4-methylphenyl)sulfonamido]-2-(p-
tolyl)ethanamine Oxide (5e)
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
White solid; yield: 4.9 mg (12%); mp 107–108 °C.
429.1035.
1H NMR (600 MHz, CDCl3):  = 7.86 (s, 1 H), 7.57 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 2.2, 1.6 Hz, 2 H), 7.38–7.42 (m, 3 H), 7.16 (d, J = 8.0 Hz, 2
H), 7.08 (d, J = 7.9 Hz, 2 H), 7.04 (d, J = 8.0 Hz, 2 H), 5.36 (d, J = 4.0 Hz,
1 H), 4.55–4.59 (m, 1 H), 4.17 (q, J = 4.2 Hz, 1 H), 4.06 (q, J = 8.8 Hz, 1
H), 2.32 (s, 3 H), 2.22 (s, 3 H).
N-{1-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-
1-phenylmethanimine Oxide (4h)
White solid; yield: 18.0 mg (42%); mp 145–146 °C.
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
409.1584.
1H NMR (600 MHz, CDCl3):  = 8.05 (s, 1 H), 7.70 (d, J = 8.2 Hz, 2 H),
7.45 (dd, J = 1.7, 1.3 Hz, 2 H), 7.32–7.37 (m, 3 H), 7.26 (d, J = 8.5 Hz, 2
H), 7.23 (d, J = 8.1 Hz, 2 H), 7.17 (d, J = 8.5 Hz, 2 H), 5.16–5.21 (m, 2 H),
3.40–3.44 (m, 1 H), 3.28–3.33 (m, 1 H), 2.37 (s, 3 H).
N-{1-(2-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-
1-phenylmethanimine Oxide (4f)
13C NMR (150 MHz, CDCl3):  = 153.2, 146.4, 139.8, 139.8, 137.0,
134.4, 133.2, 132.6, 131.6, 130.9, 130.1, 130.0, 85.4, 50.6, 24.4.
White solid; yield: 19.7 mg (46%); mp 118–119 °C.
1H NMR (600 MHz, CDCl3):  = 8.08 (s, 1 H), 7.73 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 1.7, 1.4 Hz, 2 H), 7.35–7.37 (m, 2 H), 7.32–7.35 (m, 2 H),
7.30–7.32 (m, 1 H), 7.23 (d, J = 8.1 Hz, 2 H), 7.20–7.22 (m, 2 H), 5.57 (q,
J = 3.2 Hz, 1 H), 5.05 (q, J = 4.1 Hz, 1 H), 3.57–3.62 (m, 1 H), 3.24–3.29
(m, 1 H), 2.37 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
429.
(Z)-N-{2-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]eth-
yl}-1-phenylmethanimine Oxide (5h)
13C NMR (150 MHz, CDCl3):  = 153.3, 146.2, 140.0, 139.0, 135.1,
134.4, 133.2, 132.6, 132.5, 132.1, 131.6, 130.9, 130.2, 130.1, 129.9,
83.0, 49.1, 24.4.
White solid; yield: 5.6 mg (13%); mp 147–148 °C.
1H NMR (400 MHz, CDCl3):  = 7.80 (s, 1 H), 7.64 (d, J = 7.6 Hz, 1 H),
7.48 (d, J = 7.2 Hz, 2 H), 7.39 (d, J = 7.6 Hz, 2 H), 7.34 (d, J = 6.8 Hz, 3 H),
7.23–7.17 (m, 2 H), 7.15–7.10 (m, 1 H), 6.99 (d, J = 7.6 Hz, 2 H), 5.42
(d, J = 3.2 Hz, 1 H), 4.53–4.51 (m, 1 H), 4.11 (dd, J = 9.6, 2.4 Hz, 1 H),
3.99 (dd, J = 3.6, 8.4 Hz, 1 H), 2.14 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
429.1035.
(Z)-N-{2-(2-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]eth-
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
yl}-1-phenylmethanimine Oxide (5f)
429.1035.
White solid; yield: 3.4 mg (8%); mp 131–133 °C.
1H NMR (400 MHz, CDCl3):  = 7.84 (s, 1 H), 7.75–7.68 (m, 2 H), 7.63
(d, J = 8.4 Hz, 2 H), 7.54 (q, J = 3.2 Hz, 2 H), 7.49–7.44 (m, 1 H), 7.43–
7.37 (d, J = 6.4 Hz, 2 H), 7.33–7.31 (m, 1 H), 7.21–7.19 (m, 2 H), 7.05
(d, J = 8.0 Hz, 1 H), 5.65 (d, J = 4.0 Hz, 1 H), 5.13–5.05 (m, 1 H), 4.27
(dd, J = 12.4, 3.6 Hz, 1 H), 4.00 (dd, J = 4, 8 Hz, 1 H), 2.19 (s, 3 H).
N-{2-[(4-Methylphenyl)sulfonamido]-1-(naphthalen-1-yl)ethyl}-
1-phenylmethanimine Oxide (4i)
Colorless liquid; yield: 11.6 mg (26%).
1H NMR (600 MHz, CDCl3):  = 8.14 (s, 1 H), 7.89–7.91 (m, 1 H), 7.84–
7.86 (m, 1 H), 7.77 (d, J = 8.5 Hz, 1 H), 7.71 (dt, J = 2.2, 1.9 Hz, 2 H),
7.50–7.51 (m, 2 H), 7.48–7.49 (m, 2 H), 7.47 (s, 1 H), 7.40 (t, J = 7.4 Hz,
1 H), 7.35–7.36 (m, 2 H), 7.33–7.34 (m, 1 H), 7.23 (d, J = 0.8 Hz, 1 H),
7.22 (s, 1 H), 6.01 (q, J = 3.2 Hz, 1 H), 5.18 (q, J = 3.7 Hz, 1 H), 3.65–3.70
(m, 1 H), 3.40–3.44 (m, 1 H), 2.37 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
429.1035.
N-{1-(3-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-
13C NMR (150 MHz, CDCl3):  = 153.0, 146.3, 140.1, 136.8, 136.7,
134.6, 133.4, 133.1, 132.6, 131.8, 131.6, 130.1, 130.1, 129.4, 128.6,
128.1, 127.2, 125.7, 83.7, 50.4, 24.4.
1-phenylmethanimine Oxide (4g)
Colorless liquid; yield: 21.5 mg (50%).
1H NMR (600 MHz, CDCl3):  = 8.06 (s, 1 H), 7.71 (d, J = 8.3 Hz, 2 H),
7.47 (dd, J = 1.8, 1.4 Hz, 2 H), 7.36–7.37 (m, 1 H), 7.35–7.36 (m, 1 H),
7.27 (d, J = 0.6 Hz, 1 H), 7.26 (s, 2 H), 7.24 (d, J = 1.0 Hz, 1 H), 7.20–7.22
(m, 2 H), 7.13–7.15 (m, 1 H), 5.18 (q, J = 3.8 Hz, 1 H), 5.01 (q, J = 4.2 Hz,
1 H), 3.41–3.46 (m, 1 H), 3.29–3.33 (m, 1 H), 2.39 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C26H25N2O3S: 445.1586; found:
445.1568.
(Z)-N-{2-[(4-Methylphenyl)sulfonamido]-2-(naphthalen-1-yl)eth-
13C NMR (150 MHz, CDCl3):  = 153.3, 146.5, 143.3, 139.8, 137.4,
134.3, 133.2, 132.8, 132.7, 131.6, 131.3, 130.2, 130.0, 129.6, 127.7,
85.5, 50.6, 24.4.
yl}-1-phenylmethanimine Oxide (5i)
Colorless liquid; yield: 4.9 mg (11%).
1H NMR (400 MHz, CDCl3):  = 8.08 (d, J = 8.8 Hz, 1 H), 7.93–7.88 (m, 1
H), 7.87 (d, J = 8.0 Hz, 1 H), 7.79–7.65 (m, 3 H), 7.55–7.48 (m, 6 H),
7.43–7.39 (m, 3 H), 6.99 (d, J = 8.4 Hz, 2 H), 5.50 (d J = 7.2 Hz, 1 H),
5.35 (d J = 9.2 Hz, 1 H), 4.40 (dd, J = 10.4, 3.2 Hz, 1 H), 4.13 (dd, J = 3.6,
8.4 Hz, 1 H), 2.16 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C22H22ClN2O3S: 429.1040; found:
429.1035.
(Z)-N-{2-(3-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]eth-
yl}-1-phenylmethanimine Oxide (5g)
HRMS (ESI): m/z [M + H] calcd for C26H25N2O3S: 445.1586; found:
445.1568.
Colorless liquid; yield: 6.8 mg (16%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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X. Li et al.
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Synthesis
N-{2-[(4-Methylphenyl)sulfonamido]-1-(naphthalen-2-yl)ethyl}-
1-phenylmethanimine Oxide (4j)
1H NMR (600 MHz, CDCl3):  = 7.82 (s, 1 H), 7.73 (d, J = 8.5 Hz, 2 H),
7.46–7.48 (m, 2 H), 7.36–7.38 (m, 3 H), 7.18 (d, J = 8.3 Hz, 2 H), 4.85
(d, J = 7.6 Hz, 1 H), 3.95 (qd, J = 5.6, 4.3 Hz, 2 H), 3.46–3.51 (m, 1 H),
2.31 (s, 3 H), 1.49–1.56 (m, 2 H), 1.20–1.25 (m, 24 H), 1.20–1.23 (m, 4
H), 0.86 (t, J = 6.7 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 152.1, 146.0, 141.0, 141.0, 141.0,
134.7, 133.0, 132.4, 131.6, 130.1, 129.9, 78.0, 56.8, 35.4, 34.8, 32.6,
32.6, 32.5, 32.4, 32.3, 32.2, 28.3, 25.6, 24.3, 17.0.
White solid; yield: 8.5 mg (19%); mp 107–108 °C.
1H NMR (600 MHz, CDCl3):  = 8.11 (s, 1 H), 7.79–7.82 (m, 3 H), 7.69
(d, J = 8.3 Hz, 3 H), 7.47 (td, J = 2.3, 1.4 Hz, 4 H), 7.34–7.37 (m, 4 H),
7.21 (d, J = 8.0 Hz, 2 H), 5.38 (q, J = 4.1 Hz, 1 H), 4.97 (q, J = 4.2 Hz, 1 H),
3.52–3.57 (m, 1 H), 3.43–3.48 (m, 1 H), 2.37 (s, 3 H).
13C NMR (150 MHz, CDCl3):  = 153.1, 146.4, 139.8, 138.5, 136.1,
136.0, 134.5, 133.1, 132.6, 131.6, 131.4, 130.9, 130.6, 130.1, 130.0,
129.3, 129.2, 128.9, 127.0, 86.2, 50.8, 24.4.
HRMS (ESI): m/z [M + H] calcd for C32H51N2O3S: 543.3620; found:
543.3602.
HRMS (ESI): m/z [M + H] calcd for C26H25N2O3S: 445.1586; found:
445.1586.
N-{1-Hydroxy-4-[(4-methylphenyl)sulfonamido]hexan-3-yl}-1-
phenylmethanimine Oxide (5n)
White solid; yield: 18.0 mg (46%); mp 100–101 °C.
(Z)-N-{2-[(4-Methylphenyl)sulfonamido]-2-(naphthalen-2-yl)eth-
yl}-1-phenylmethanimine Oxide (5j)
1H NMR (600 MHz, CDCl3):  = 7.95 (s, 1 H), 7.76 (d, J = 8.4 Hz, 2 H),
7.51 (d, J = 2.2 Hz, 1 H), 7.50–7.51 (m, 1 H), 7.40 (d, J = 1.8 Hz, 2 H),
7.39–7.38 (m, 1 H), 7.26 (d, J = 8.1 Hz, 2 H), 4.98 (d, J = 8.9 Hz, 1 H),
4.38–4.41 (m, 1 H), 3.68–3.76 (m, 2 H), 3.40–3.45 (m, 1 H), 2.40 (s, 3
H), 2.00 (s, 1 H), 1.87–1.93 (m, 1 H), 1.76–1.81 (m, 1 H), 1.63–1.69 (m,
1 H), 1.38–1.43 (m, 1 H), 0.80 (t, J = 7.6 Hz, 2 H).
White solid; yield: 3.6 mg (8%); mp 119–120 °C.
1H NMR (400 MHz, CDCl3):  = 7.93 (s, 1 H), 7.89 (d, J = 6.8 Hz, 2 H),
7.76–7.67 (m, 5 H), 7.58–7.41 (m, 5 H), 7.35 (t, J = 5.2 Hz, 2 H), 6.97 (d,
J = 7.6 Hz, 2 H), 5.54 (d, J = 2.8 Hz, 1 H), 5.40–5.34 (m, 1 H), 4.81 (t, J =
4.0 Hz, 1 H), 4.21 (dd, J = 3.6, 8.4 Hz, 1 H), 2.16 (s, 3 H).
13C NMR (150 MHz, CDCl3):  = 152.1, 146.1, 141.3, 134.6, 133.1,
132.5, 131.7, 83.7, 62.5, 61.3, 36.6, 32.6, 28.2, 24.4, 13.1.
HRMS (ESI): m/z [M + H] calcd for C26H25N2O3S: 445.1586; found:
445.1586.
HRMS (ESI): m/z [M + H] calcd for C20H27N2O4S: 391.1692; found:
391.1680.
N-{2-[(4-Methylphenyl)sulfonamido]cyclopentyl}-1-phenylmeth-
animine Oxide (5k)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-phenylethan-
1-imine Oxide (3a′)
White solid; yield: 29.8 mg (83%); mp 99–100 °C.
1H NMR (600 MHz, CDCl3):  = 7.85 (s, 1 H), 7.70 (d, J = 8.3 Hz, 2 H),
7.48–7.50 (m, 2 H), 7.37–7.41 (m, 3 H), 7.10 (d, J = 7.9 Hz, 2 H), 5.23
(d, J = 4.3 Hz, 1 H), 4.45–4.49 (m, 1 H), 3.48–3.52 (m, 1 H), 2.30 (s, 3
H), 2.09–2.15 (m, 1 H), 1.97–2.02 (m, 1 H), 1.67–1.73 (m, 3 H), 1.57–
1.62 (m, 1 H).
13C NMR (150 MHz, CDCl3):  = 151.9, 146.1, 146.0, 140.0, 139.9,
134.9, 133.0, 133.0, 132.4, 131.6, 130.2, 129.9, 90.9, 90.9, 62.6, 34.2,
31.3, 24.4, 24.3, 23.8.
White solid; yield: 38.3 mg (99%) (0.1 mmol scale), 0.93 g (97%) (2.5
mmol scale); mp 120–121 °C.
1H NMR (600 MHz, CDCl3):  = 7.63 (d, J = 8.3 Hz, 2 H), 7.54–7.57 (m, 2
H), 7.36–7.39 (m, 3 H), 7.13 (d, J = 8.0 Hz, 2 H), 5.56 (d, J = 3.1 Hz, 1 H),
3.90–3.95 (m, 1 H), 3.11–3.16 (m, 1 H), 2.32–2.35 (m, 4 H), 2.02–2.06
(m, 1 H), 1.93 (s, 3 H), 1.71–1.75 (m, 1 H), 1.64–1.66 (m, 1 H), 1.31–
1.40 (m, 2 H), 1.23–1.28 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 157.8, 145.8, 140.3, 138.8, 132.3,
132.3, 131.4, 130.0, 128.8, 85.6, 60.8, 35.9, 33.6, 27.0, 26.8, 24.4, 15.4.
HRMS (ESI): m/z [M + H] calcd for C19H23N2O3S: 359.1429; found:
359.1422.
HRMS (ESI): m/z [M + H] calcd for C21H27N2O3S: 387.1742; found:
387.1734.
N-{2-[(4-Methylphenyl)sulfonamido]octyl}-1-phenylmethani-
mine Oxide (5l)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-phenylpro-
pan-1-imine Oxide (3b′)
White solid; yield: 27.2 mg (69%); mp 76–77 °C.
1H NMR (600 MHz, CDCl3):  = 7.83 (s, 1 H), 7.73 (d, J = 8.3 Hz, 2 H),
7.47–7.49 (m, 2 H), 7.36–7.39 (m, 3 H), 7.19 (d, J = 8.1 Hz, 2 H), 4.86
(d, J = 7.7 Hz, 1 H), 3.96 (qd, J = 5.5, 4.3 Hz, 2 H), 3.46 (m, 1 H), 2.32 (s,
3 H), 1.50–1.56 (m, 2 H), 1.24–1.32 (m, 4 H), 1.20–1.23 (m, 4 H), 0.85
(t, J = 7.1 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 152.1, 146.0, 146.0, 141.0, 140.9,
134.7, 133.0, 132.4, 131.6, 130.1, 129.9, 78.0, 56.8, 35.4, 34.5, 31.9,
28.2, 25.4, 25.4, 24.3, 24.3, 17.0, 16.9, 24.4.
Colorless liquid; yield: 39.7 mg (99%).
1H NMR (600 MHz, CDCl3):  = 7.64 (d, J = 8.1 Hz, 2 H), 7.54–7.56 (m, 2
H), 7.37 (t, J = 3.5 Hz, 3 H), 7.14 (d, J = 8.0 Hz, 2 H), 5.61 (d, J = 2.5 Hz, 1
H), 3.89–3.94 (m, 1 H), 3.12–3.17 (m, 1 H), 2.44–2.51 (m, 2 H), 2.34–
2.37 (m, 1 H), 2.33 (s, 3 H), 2.03–2.06 (m, 1 H), 1.71–1.74 (m, 1 H),
1.62–1.66 (m, 1 H), 1.32–1.40 (m, 2 H), 1.23–1.31 (m, 2 H), 0.96 (t, J =
7.4 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 162.9, 145.8, 140.2, 137.8, 132.3,
132.2, 131.5, 130.0, 129.0, 85.4, 60.7, 35.7, 33.5, 26.9, 26.7, 24.3, 22.8,
13.9.
HRMS (ESI): m/z [M + H] calcd for C22H31N2O3S: 403.2055; found:
403.2054.
HRMS (ESI): m/z [M + H] calcd for C22H29N2O3S: 401.1899; found:
401.1892.
N-{2-[(4-Methylphenyl)sulfonamido]octadecyl}-1-phenylmeth-
animine Oxide (5m)
White solid; yield: 37.6 mg (73%); mp 85–86 °C.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(o-
tolyl)ethan-1-imine Oxide (3c′)
Colorless liquid; yield: 33.2 mg (83%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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X. Li et al.
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Synthesis
1H NMR (600 MHz, CDCl3):  = 7.73 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 8.3
Hz, 3 H), 7.18–7.21 (m, 3 H), 5.29 (d, J = 3.4 Hz, 1 H), 3.88–3.93 (m, 1
H), 3.15–3.20 (m, 1 H), 2.39 (s, 3 H), 2.32 (s, 3 H), 2.23–2.26 (m, 1 H),
2.08–2.11 (m, 1 H), 1.99 (s, 3 H), 1.70–1.73 (m, 1 H), 1.62–1.63 (m, 1
H), 1.31–1.40 (m, 2 H), 1.23–1.26 (m, 2 H).
1H NMR (600 MHz, CDCl3):  = 7.63 (d, J = 8.3 Hz, 2 H), 7.48 (dt, J = 2.4,
1.9 Hz, 2 H), 7.41 (dt, J = 2.3, 1.9 Hz, 2 H), 7.13 (d, J = 8.0 Hz, 2 H), 5.39
(d, J = 4.3 Hz, 1 H), 3.89–3.94 (m, 1 H), 3.14–3.19 (m, 1 H), 2.34 (s, 3
H), 2.28–2.32 (m, 1 H), 2.02–2.06 (m, 1 H), 1.93 (s, 3 H), 1.71–1.74 (m,
1 H), 1.63–1.66 (m, 1 H), 1.31–1.42 (m, 2 H), 1.24–1.28 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 160.7, 145.9, 140.7, 139.8, 138.6,
133.7, 132.4, 131.5, 131.0, 130.0, 128.8, 85.7, 60.3, 35.5, 33.9, 26.9,
26.8, 24.4, 23.3, 19.3.
13C NMR (150 MHz, CDCl3):  = 156.8, 145.9, 140.4, 137.8, 134.5,
132.3, 130.3, 130.0, 126.5, 85.9, 60.4, 35.8, 33.5, 29.8, 26.9, 26.8, 24.4,
15.2.
HRMS (ESI): m/z [M + H] calcd for C22H29N2O3S: 401.1899; found:
HRMS (ESI): m/z [M + H] calcd for C21H26BrN2O3S: 465.0848; found:
401.1894.
465.0838.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(m-
tolyl)ethan-1-imine Oxide (3d′)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(2-nitrophe-
nyl)ethan-1-imine Oxide (3h′)
Colorless liquid; yield: 36.0 mg (90%).
Yellow liquid; yield: 32.4 mg (75%).
1H NMR (600 MHz, CDCl3):  = 7.63 (d, J = 8.3 Hz, 2 H), 7.38 (s, 1 H),
7.33 (d, J = 7.9 Hz, 1 H), 7.25 (t, J = 7.6 Hz, 1 H), 7.19 (d, J = 7.5 Hz, 1 H),
7.14 (d, J = 8.0 Hz, 2 H), 5.61 (d, J = 2.9 Hz, 1 H), 3.91–3.95 (m, 1 H),
3.09–3.14 (m, 1 H), 2.39 (s, 3 H), 2.33–2.36 (s, 4 H), 2.04–2.07 (m, 1
H), 1.92 (s, 3 H), 1.72–1.75 (m, 1 H), 1.64–1.67 (m, 1 H), 1.34–1.41 (m,
2 H), 1.24–1.28 (m, 2 H).
1H NMR (600 MHz, CDCl3):  = 7.97 (q, J = 1.0 Hz, 1 H), 7.76 (d, J = 8.2
Hz, 2 H), 7.64 (td, J = 1.1, 1.1 Hz, 1 H), 7.53 (td, J = 1.4, 0.7 Hz, 1 H), 7.44
(q, J = 1.3 Hz, 1 H), 7.27 (d, J = 8.0 Hz, 2 H), 5.20 (d, J = 4.0 Hz, 1 H),
3.87–3.92 (m, 1 H), 3.15–3.20 (m, 1 H), 2.41 (s, 3 H), 2.19–2.22 (m, 1
H), 2.06–2.08 (m, 1 H), 1.98 (s, 3 H), 1.69–1.72 (m, 1 H), 1.60–1.62 (m,
1 H), 1.28–1.39 (m, 2 H), 1.18–1.25 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 158.1, 145.8, 141.0, 140.3, 138.8,
133.1, 132.3, 131.3, 130.0, 129.4, 126.0, 85.6, 60.9, 36.0, 33.6, 27.0,
26.8, 24.4, 24.4, 15.5.
HRMS (ESI): m/z [M + H] calcd for C21H26N3O5S: 432.1593; found:
432.1595.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(3-nitrophe-
nyl)ethan-1-imine Oxide (3i′)
HRMS (ESI): m/z [M + H] calcd for C22H29N2O3S: 401.1899; found:
401.1892.
White solid; yield: 35.0 mg (81%); mp 121–122 °C.
1H NMR (600 MHz, CDCl3):  = 8.36 (t, J = 2.0 Hz, 1 H), 8.21 (dq, J = 1.0,
0.9 Hz, 1 H), 7.91–7.94 (m, 1 H), 7.67 (d, J = 8.3 Hz, 2 H), 7.54 (t, J = 8.0
Hz, 1 H), 7.17 (q, J = 0.5 Hz, 2 H), 5.22 (d, J = 4.4 Hz, 1 H), 3.95–4.00 (m,
1 H), 3.23–3.28 (m, 1 H), 2.34 (s, 3 H), 2.23–2.27 (m, 1 H), 2.06–2.10
(m, 1 H), 2.02 (s, 3 H), 1.73–1.76 (m, 1 H), 1.64–1.67 (m, 1 H), 1.41–
1.48 (m, 1 H), 1.31–1.36 (m, 1 H), 1.24–1.30 (m, 2 H).
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(p-
tolyl)ethan-1-imine Oxide (3e′)
Colorless liquid; yield: 38.9 mg (97%).
1H NMR (600 MHz, CDCl3):  = 7.61 (d, J = 8.2 Hz, 2 H), 7.45 (d, J = 8.3
Hz, 2 H), 7.17 (d, J = 8.1 Hz, 2 H), 7.13 (d, J = 8.1 Hz, 2 H), 5.67 (d, J = 2.7
Hz, 1 H), 3.89–3.94 (m, 1 H), 3.07–3.12 (m, 1 H), 2.38 (s, 3 H), 2.35–
2.37 (m, 1 H), 2.34 (s, 3 H), 2.02–2.05 (m, 1 H), 1.90 (s, 3 H), 1.71–1.75
(m, 1 H), 1.64–1.66 (m, 1 H), 1.31–1.40 (m, 2 H), 1.21–1.28 (m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C21H26N3O5S: 432.1593; found:
432.1583.
13C NMR (150 MHz, CDCl3):  = 157.8, 145.8, 142.3, 140.2, 136.0,
132.3, 132.1, 130.0, 128.7, 85.5, 61.0, 36.0, 33.5, 27.0, 26.8, 24.4, 24.2,
15.3.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(4-nitrophe-
nyl)ethan-1-imine Oxide (3j′)
Yellow liquid; yield: 32.8 mg (76%).
HRMS (ESI): m/z [M + H] calcd for C22H29N2O3S: 401.1899; found:
1H NMR (600 MHz, CDCl3):  = 8.20 (dt, J = 2.5, 2.2 Hz, 2 H), 7.71 (dt,
J = 2.5, 1.7 Hz, 2 H), 7.66 (d, J = 8.3 Hz, 2 H), 7.17 (d, J = 7.9 Hz, 2 H),
5.21 (d, J = 4.4 Hz, 1 H), 3.96–4.00 (m, 1 H), 3.22–3.27 (m, 1 H), 2.34 (s,
3 H), 2.23–2.26 (m, 1 H), 2.06–2.09 (m, 1 H), 2.01 (s, 3 H), 1.73–1.76
(m, 1 H), 1.64–1.67 (m, 1 H), 1.41–1.48 (m, 2 H), 1.28–1.34 (m, 2 H).
401.1893.
1-(4-Chlorophenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}ethan-1-imine Oxide (3f′)
Colorless liquid; yield: 40.0 mg (95%).
HRMS (ESI): m/z [M + H] calcd for C21H26N3O5S: 432.1593; found:
432.1589.
1H NMR (600 MHz, CDCl3):  = 7.62 (dt, J = 2.2, 1.9 Hz, 2 H), 7.48 (dt,
J = 2.3, 2.2 Hz, 2 H), 7.32 (dt, J = 2.3, 2.2 Hz, 2 H), 7.13 (q, J = 0.6 Hz, 2
H), 5.42 (d, J = 3.5 Hz, 1 H), 3.89–3.94 (m, 1 H), 3.13–3.19 (m, 1 H),
2.34 (s, 3 H), 2.28–2.33 (m, 1 H), 2.02–2.06 (m, 1 H), 1.93 (s, 3 H),
1.71–1.75 (m, 1 H), 1.63–1.67 (m, 1 H), 1.33–1.41 (m, 2 H), 1.27–1.31
(m, 2 H).
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(naphthalen-
2-yl)ethan-1-imine Oxide (3k′)
White solid; yield: 41.0 mg (94%); mp 132–133 °C.
13C NMR (150 MHz, CDCl3):  = 156.7, 145.9, 140.4, 138.2, 137.3,
132.3, 131.6, 130.0, 129.9, 85.8, 60.5, 35.9, 33.5, 26.9, 26.8, 24.4, 15.2.
1H NMR (600 MHz, CDCl3):  = 7.92 (d, J = 1.0 Hz, 1 H), 7.87 (q, J = 3.5
Hz, 1 H), 7.84 (q, J = 3.3 Hz, 1 H), 7.81 (d, J = 8.7 Hz, 1 H), 7.79 (d, J = 1.7
Hz, 1 H), 7.62 (d, J = 8.3 Hz, 2 H), 7.50–7.53 (m, 2 H), 7.09 (d, J = 8.0 Hz,
2 H), 5.60 (d, J = 2.8 Hz, 1 H), 3.95–4.00 (m, 1 H), 3.14–3.19 (m, 1 H),
2.36–2.39 (m, 1 H), 2.27 (s, 3 H), 2.06–2.10 (m, 1 H), 2.04 (s, 3 H),
1.74–1.77 (m, 1 H), 1.66–1.69 (m, 1 H), 1.38–1.45 (m, 2 H), 1.24–1.33
(m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C21H26ClN2O3S: 421.1353; found:
421.1343.
1-(4-Bromophenyl)-N-{2-[(4-methylphenyl)sulfonamido]cyclo-
hexyl}ethan-1-imine Oxide (3g′)
HRMS (ESI): m/z [M + H] calcd for C25H29N2O3S: 437.1899; found:
437.1891.
Colorless liquid; yield: 46.1 mg (99%).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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X. Li et al.
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Synthesis
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1,2-dipheny-
lethan-1-imine Oxide (3l′)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}hexan-2-imine
Oxide (3p′)
Colorless liquid; yield: 45.8 mg (99%).
Colorless liquid; yield: 11.7 mg (32%).
1H NMR (600 MHz, CDCl3):  = 7.58 (d, J = 8.3 Hz, 2 H), 7.55 (d, J = 1.6
Hz, 1 H), 7.54–7.55 (m, 1 H), 7.30–7.34 (m, 3 H), 7.22 (d, J = 7.6 Hz, 2
H), 7.16 (t, J = 7.4 Hz, 1 H), 7.08–7.10 (m, 4 H), 5.41 (d, J = 3.2 Hz, 1 H),
3.96–4.00 (m, 1 H), 3.86 (d, J = 14.6 Hz, 1 H), 3.77 (d, J = 14.6 Hz, 1 H),
3.11–3.16 (m, 1 H), 2.31–2.34 (m, 1 H), 2.30 (s, 3 H), 2.03–2.06 (m, 1
H), 1.68–1.71 (m, 1 H), 1.62–1.64 (m, 1 H), 1.30–1.38 (m, 2 H), 1.19–
1.29 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 159.5, 145.9, 140.2, 139.3, 138.0,
132.4, 132.3, 131.6, 131.4, 131.2, 130.0, 129.3, 85.9, 60.1, 35.5, 33.5,
26.8, 26.6, 24.4.
1H NMR (600 MHz, CDCl3):  = 7.70 (d, J = 8.3 Hz, 2 H), 7.2 (d, J = 8.0
Hz, 2 H), 5.69 (d, J = 2.4 Hz, 1 H), 3.74–3.78 (m, 1 H), 2.99–3.04 (m, 1
H), 2.41 (s, 3 H), 2.26–2.30 (m, 1 H), 2.07–2.11 (m, 2 H), 1.96–1.98 (m,
1 H), 1.67–1.70 (m, 1 H), 1.59–1.62 (m, 1 H), 1.56 (s, 3 H), 1.41–1.46
(m, 2 H), 1.30–1.34 (m, 2 H), 1.22–124 (m, 2 H), 1.24–1.29 (m, 2 H),
0.92 (t, J = 7.3 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 161.3, 145.7, 140.7, 132.2, 130.0, 84.7,
61.2, 38.5, 35.7, 33.6, 31.2, 27.0, 26.8, 25.2, 24.3, 16.9, 16.7.
HRMS (ESI): m/z [M + H] calcd for C19H31N2O3S: 367.2055; found:
367.2049.
HRMS (ESI): m/z [M + H] calcd for C27H31N2O3S: 463.2055; found:
463.2042.
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}cyclohexani-
mine Oxide (3q′)
1-(Furan-2-yl)-N-{2-[(4-methylphenyl)sulfonamido]cyclohex-
yl}ethan-1-imine Oxide (3m′)
Colorless liquid; yield: 17.1 mg (47%).
1H NMR (600 MHz, CDCl3):  = 7.71 (d, J = 8.2 Hz, 2 H), 7.26 (d, J = 8.0
Hz, 2 H), 5.65 (d, J = 1.9 Hz, 1 H), 3.71–3.76 (m, 1 H), 2.99–3.04 (m, 1
H), 2.42 (s, 3 H), 2.24–2.29 (m, 2 H), 2.11–2.14 (m, 3 H), 1.97–2.00 (m,
1 H), 1.65–1.70 (m, 2 H), 1.60–1.64 (m, 2 H), 1.56–1.59 (m, 2 H), 1.50–
1.54 (m, 2 H), 1.15–1.32 (m, 4 H).
13C NMR (150 MHz, CDCl3):  = 163.6, 145.7, 140.8, 132.3, 130.0, 84.6,
61.0, 35.7, 34.9, 33.6, 29.7, 28.6, 28.4, 28.1, 26.9, 26.8, 24.4.
Yellow solid; yield: 30.9 mg (82%); mp 131–133 °C.
1H NMR (600 MHz, CDCl3):  = 7.61 (d, J = 8.2 Hz, 2 H), 7.43–7.44 (m, 1
H), 7.06 (d, J = 8.0 Hz, 2 H), 6.87 (d, J = 3.4 Hz, 1 H), 6.41 (q, J = 1.8 Hz,
1 H), 5.55 (d, J = 2.9 Hz, 1 H), 3.88–3.92 (m, 1 H), 3.08–3.13 (m, 1 H),
2.32–2.36 (m, 1 H), 2.28 (s, 3 H), 2.14 (s, 3 H), 2.04–2.07 (m, 1 H),
1.72–1.76 (m, 1 H), 1.64–1.67 (m, 1 H), 1.33–1.40 (m, 2 H), 1.24–1.27
(m, 2 H).
HRMS (ESI): m/z [M + H] calcd for C19H29N2O3S: 365.1899; found:
365.1895.
13C NMR (150 MHz, CDCl3):  = 148.7, 146.6, 145.7, 145.4, 140.2,
132.1, 129.9, 120.7, 114.8, 86.3, 61.3, 36.1, 33.7, 27.0, 26.8, 24.3, 20.1.
HRMS (ESI): m/z [M + H] calcd for C19H25N2O4S: 377.1535; found:
377.1529.
N-{2-[(4-Methylphenyl)sulfonamido]-1-phenylethyl}-1-pheny-
lethan-1-imine Oxide (4b′) and N-{2-[(4-Methylphenyl)sulfonami-
do]-2-phenylethyl}-1-phenylethan-1-imine Oxide (5b′)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}-1-(thiophen-2-
yl)ethan-1-imine Oxide (3n′)
Colorless liquid; yield: 23.7 mg (58%).
1H NMR (600 MHz, CDCl3):  = 7.54–7.56 (m, 4 H), 7.40–7.41 (d, J = 1.9
Hz, 2 H), 7.39–7.40 (d, J = 2.2 Hz, 1 H), 7.34–7.36 (m, 1 H), 7.27–7.29
(m, 3 H), 7.25–7.26 (m, 2 H), 7.24–7.25 (m, 1 H), 7.06–7.07 (d, J = 8.0
Hz, 2 H), 5.64–5.65 (d, J = 3.8 Hz, 1 H), 5.25–5.27 (dd, J = 3.6, 8.4 Hz,
0.2 H), 5.06–5.08 (dd, J = 4.2, 8.4 Hz, 0.2 H), 4.60–4.63 (m, 1 H), 4.20–
4.23 (dd, J = 4.0, 4.0 Hz, 1 H), 4.11–4.15 (dd, J = 8.7, 8.8 Hz, 1 H), 3.45–
3.50 (m, 0.2 H), 3.37–3.41 (m, 0.2 H), 2.39 (s, 0.6 H), 2.25 (s, 3 H), 2.24
(s, 0.6 H), 2.09 (s, 3 H).
White solid; yield: 24.7 mg (93%); mp 121–122 °C.
1H NMR (600 MHz, CDCl3):  = 7.62 (d, J = 8.2 Hz, 2 H), 7.29 (q, J = 1.0
Hz, 1 H), 7.17 (q, J = 1.1 Hz, 1 H), 7.12 (d, J = 8.0 Hz, 2 H), 7.02 (dd, J =
3.8, 3.6 Hz, 1 H), 5.53 (d, J = 3.1 Hz, 1 H), 3.85–3.90 (m, 1 H), 3.08–3.13
(m, 1 H), 2.35 (s, 3 H), 2.31–2.33 (m, 1 H), 2.01–2.03 (m, 1 H), 1.90 (s,
3 H), 1.72–1.74 (m, 1 H), 1.64–1.66 (m, 1 H), 1.33–1.40 (m, 2 H), 1.24–
1.28 (m, 2 H).
13C NMR (150 MHz, CDCl3):  = 153.7, 145.7, 142.8, 140.3, 132.2,
HRMS (ESI): m/z [M + H] calcd for C23H25N2O3S: 409.1586; found:
130.2, 130.0, 129.9, 129.2, 85.6, 60.9, 36.2, 33.4, 27.0, 26.8, 24.3, 15.6.
409.1580.
HRMS (ESI): m/z [M + H] calcd for C19H25N2O3S2: 393.1307; found:
393.1304.
N-{2-[(4-Methylphenyl)sulfonamido]-1-(m-tolyl)ethyl}-1-pheny-
lethan-1-imine Oxide (4c′) and N-{2-[(4-Methylphenyl)sulfonami-
do]-2-(m-tolyl)ethyl}-1-phenylethan-1-imine Oxide (5c′)
N-{2-[(4-Methylphenyl)sulfonamido]cyclohexyl}butan-2-imine
Oxide (3o′)
White solid; yield: 27.9 mg (66%); mp 102–103 °C.
White solid; yield: 12.9 mg (38%); mp 53–54 °C.
1H NMR (600 MHz, CDCl3):  = 7.56–7.57 (d, J = 2.2 Hz, 1 H), 7.55–7.56
(m, 1 H), 7.53–7.55 (d, J = 8.3 Hz, 2 H), 7.40–7.41 (d, J = 2.0 Hz, 2 H),
7.39–7.40 (d, J = 1.9 Hz, 1 H), 7.15–7.18 (t, J = 7.8 Hz, 1 H), 7.08–7.10
(m, 1 H), 7.06–7.07 (d, J = 0.6 Hz, 1 H), 7.05–7.06 (d, J = 0.7 Hz, 1 H),
7.03–7.04 (m, 2 H), 5.59–5.61 (d, J = 4.4 Hz, 1 H), 5.20–5.22 (dd, J = 4.2,
8.4 Hz, 0.17 H), 5.03–5.05 (dd, J = 4.2, 7.8 Hz, 0.17 H), 4.58–4.61 (m, 1
H), 4.21–4.22 (dd, J = 4.1, 4.0 Hz, 1 H), 4.10–4.14 (dd, J = 8.9, 8.8 Hz, 1
H), 3.44–3.48 (m, 0.17 H), 3.36–3.40 (m, 0.17 H), 2.39 (s, 0.5 H), 2.33
(s, 0.5 H), 2.27 (s, 3 H), 2.25 (s, 3 H), 2.24 (s, 0.5 H), 2.09 (s, 3 H).
1H NMR (600 MHz, CDCl3):  = 7.69 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 9.1
Hz, 2 H), 5.79 (d, J = 2.0 Hz, 1 H), 3.75–3.79 (m, 1 H), 2.97–3.02 (m, 1
H), 2.42 (s, 3 H), 2.27–2.31 (m, 1 H), 2.11 (q, J = 7.6 Hz, 2 H), 1.96–1.99
(m, 1 H), 1.68–1.71 (m, 1 H), 1.60–1.63 (m, 1 H), 1.56 (s, 3 H), 1.28–
1.32 (m, 1 H), 1.22–1.27 (m, 2 H), 1.15–1.21 (m, 1 H), 1.05–1.08 (t, J =
7.2 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 162.1, 145.8, 140.4, 132.3, 130.0, 84.7,
61.5, 35.8, 33.5, 32.1, 27.0, 26.8, 24.4, 16.8, 13.6.
HRMS (ESI): m/z [M + H] calcd for C24H27N2O3S: 423.1742; found:
423.1738.
HRMS (ESI): m/z [M + H] calcd for C17H27N2O3S: 339.1742; found:
339.1749.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

N
X. Li et al.
Paper
Synthesis
N-{2-[(4-Methylphenyl)sulfonamido]-1-(p-tolyl)ethyl}-1-pheny-
lethan-1-imine Oxide (4d′) and N-{2-[(4-Methylphenyl)sulfonami-
do]-2-(p-tolyl)ethyl}-1-phenylethan-1-imine Oxide (5d′)
H), 4.07–4.11 (dd, J = 8.6, 8.6 Hz, 1 H), 3.44–3.48 (m, 0.2 H), 3.33–3.38
(m, 0.2 H), 2.41 (s, 0.5 H), 2.39 (s, 0.6 H), 2.25 (s, 3 H), 2.23 (s, 0.6 H),
2.09 (s, 3 H).
Colorless liquid; yield: 24.5 mg (58%).
HRMS (ESI): m/z [M + H] calcd for C23H24ClN2O3S: 443.1196; found:
1H NMR (600 MHz, CDCl3):  = 7.69–7.71 (d, J = 8.3 Hz, 1 H), 7.55–7.56
(m, 2 H), 7.54–7.55 (t, J = 1.8 Hz, 3 H), 7.40–7.41 (d, J = 1.9 Hz, 2 H),
7.39–7.40 (m, 1 H), 7.34–7.36 (m, 1 H), 7.08–7.10 (m, 1 H), 7.17–7.19
(d, J = 8.0 Hz, 2 H), 7.13–7.14 (d, J = 2.5 Hz, 1 H), 7.08–7.10 (d, J = 8.0
Hz, 2 H), 7.06–7.07 (d, J = 8.0 Hz, 2 H), 5.57–5.58 (d, J = 3.7 Hz, 1 H),
5.21–5.23 (dd, J = 3.6, 7.8 Hz, 0.33 H), 5.03–5.05 (dd, J = 4.2, 7.8 Hz,
0.33 H), 4.54–4.57 (m, 1 H), 4.17–4.21 (dd, J = 4.0, 4.1 Hz, 1 H), 4.10–
4.14 (dd, J = 8.8, 8.8 Hz, 1 H), 3.43–3.47 (m, 0.33 H), 3.37–3.41 (m,
0.33 H), 2.39 (s, 1 H), 2.33 (s, 1 H), 2.32 (s, 3 H), 2.25 (s, 3 H), 2.22 (s, 1
H), 2.09 (s, 3 H).
443.1198.
N-{2-[(4-Methylphenyl)sulfonamido]-1-(naphthalen-2-yl)ethyl}-
1-phenylethan-1-imine Oxide (4h′) and N-{2-[(4-Methylphe-
nyl)sulfonamido]-2-(naphthalen-2-yl)ethyl}-1-phenylethan-1-
imine Oxide (5h′)
Yellowish solid; yield: 41.7 mg (91%); mp 38–39 °C.
1H NMR (600 MHz, CDCl3):  = 7.78–7.80 (m, 2 H), 7.72–7.75 (m, 2 H),
7.70–7.71 (m, 2 H), 7.68–7.69 (m, 1 H), 7.57–7.58 (m, 1 H), 7.56–7.57
(m, 1 H), 7.53–7.54 (m, 3 H), 7.45–7.47 (m, 2 H), 7.40–7.41 (d, J = 1.7
Hz, 2 H), 7.39–7.40 (d, J = 2.8 Hz, 1 H), 7.38–7.39 (m, 1 H), 7.32–7.35
(m, 1 H), 7.19–7.21 (dd, J = 0.5, 0.6 Hz, 1 H), 6.96–6.98 (d, J = 7.8 Hz, 2
H), 5.77–5.78 (d, J = 3.8 Hz, 1 H), 5.41–5.43 (dd, J = 4.2, 8.4 Hz, 0.33 H),
5.10–5.12 (dd, J = 3.6, 7.8 Hz, 0.33 H), 4.79–4.82 (m, 1 H), 4.28–4.31
(dd, J = 4.1, 4.0 Hz, 1 H), 4.21–4.25 (dd, J = 8.6, 8.6 Hz, 1 H), 3.59–3.55
(m, 0.33 H), 3.47–3.51 (m, 0.33 H), 2.36 (s, 1 H), 2.28 (s, 1 H), 2.16 (s, 3
H), 2.11 (s, 3 H).
HRMS (ESI): m/z [M + H] calcd for C24H27N2O3S: 423.1742; found:
423.1724.
N-{1-(3-Methoxyphenyl)-2-[(4-methylphenyl)sulfonamido]eth-
yl}-1-phenylethan-1-imine Oxide (4e′) and N-{2-(3-Methoxyphe-
nyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-1-phenylethan-1-
imine Oxide (5e′)
White solid; yield: 27.6 mg (63%); mp 96–97 °C.
HRMS (ESI): m/z [M + H] calcd for C27H27N2O3S: 459.1742; found:
1H NMR (600 MHz, CDCl3):  = 7.56–7.57 (d, J = 2.0 Hz, 1 H), 7.55–7.56
(d, J = 4.0 Hz, 2 H), 7.54 (s, 1 H), 7.40–7.41 (d, J = 1.9 Hz, 2 H), 7.39–
7.40 (d, J = 1.9 Hz, 1 H), 7.18–7.21 (t, J = 7.9 Hz, 1 H), 7.06–7.08 (d, J =
8.0 Hz, 2 H), 6.88–6.90 (d, J = 7.6 Hz, 1 H), 6.77–6.80 (m, 2 H), 5.64–
5.65 (d, J = 3.7 Hz, 1 H), 5.21–5.23 (dd, J = 4.2, 8.4 Hz, 0.17 H), 5.04–
5.06 (dd, J = 4.2, 8.4 Hz, 0.17 H), 4.59–4.62 (m, 1 H), 4.20–4.23 (dd, J =
4.0, 4.0 Hz, 1 H), 4.11–4.15 (dd, J = 8.8, 8.8 Hz, 1 H), 3.78 (s, 0.2 H),
3.74 (s, 3 H), 3.45–3.49 (m, 0.07 H), 3.35–3.39 (m, 0.07 H), 2.39 (s, 0.2
H), 2.25 (s, 3 H), 2.24 (s, 0.2 H), 2.10 (s, 3 H).
459.1736.
N-{2-[(4-Methylphenyl)sulfonamido]cyclopentyl}-1-pheny-
lethan-1-imine Oxide (5i′)
Colorless liquid; yield: 35.0 mg (94%).
1H NMR (600 MHz, CDCl3):  = 7.64 (dt, J = 2.1, 2.0 Hz, 2 H), 7.56–7.58
(m, 2 H), 7.38–7.41 (m, 3 H), 7.11 (d, J = 0.7 Hz, 1 H), 7.10 (s, 1 H), 5.35
(d, J = 3.9 Hz, 1 H), 4.47–4.51 (m, 1 H), 3.42–3.47 (m, 1 H), 2.33 (s, 3
H), 2.10–2.17 (m, 1 H), 2.07 (s, 3 H), 1.98–2.04 (m, 1 H), 1.68–1.74 (m,
3 H), 1.57–1.63 (m, 1 H).
HRMS (ESI): m/z [M + Na] calcd for C24H26N2O4SNa: 461.1511; found:
461.1511.
13C NMR (150 MHz, CDCl3):  = 158.0, 146.0, 139.9, 139.1, 132.3,
132.2, 131.4, 130.2, 128.8, 90.5, 63.1, 34.2, 31.2, 24.3, 23.7, 15.4.
N-{1-(3-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-
1-phenylethan-1-imine Oxide (4f′) and N-{2-(3-Chlorophenyl)-2-
[(4-methylphenyl)sulfonamido]ethyl}-1-phenylethan-1-imine
Oxide (5f′)
HRMS (ESI): m/z [M + H] calcd for C20H25N2O3S: 373.1586; found:
373.1578.
N-{2-[(4-Methylphenyl)sulfonamido]octyl}-1-phenylethan-1-
imine Oxide (5j′)
White solid; yield: 23.7 mg (54%); mp 104–105 °C.
1H NMR (600 MHz, CDCl3):  = 7.56–7.57 (d, J = 1.8 Hz, 1 H), 7.55–7.56
(m, 1 H), 7.53–7.55 (t, J = 8.2 Hz, 2 H), 7.39–7.43 (m, 3 H), 7.20–7.22
(m, 4 H), 7.07–7.09 (d, J = 7.9 Hz, 2 H), 5.68–5.69 (d, J = 3.6 Hz, 1 H),
5.22–5.24 (dd, J = 3.6, 7.8 Hz, 0.16 H), 5.01–5.03 (dd, J = 3.6, 8.4 Hz,
0.16 H), 4.59–4.62 (m, 1 H), 4.18–4.21 (dd, J = 3.8, 3.8 Hz, 1 H), 4.07–
4.11 (dd, J = 8.6, 8.6 Hz, 1 H), 3.44–3.48 (m, 0.17 H), 3.33–3.36 (m,
0.17 H), 2.41 (s, 0.5 H), 2.26 (s, 3 H), 2.25 (s, 0.5 H), 2.10 (s, 3 H).
White solid; yield: 22.0 mg (54%); mp 83–84 °C.
1H NMR (600 MHz, CDCl3):  = 7.72 (dt, J = 2.0, 1.7 Hz, 2 H), 7.56 (d, J =
2.5 Hz, 1 H), 7.55 (dt, J = 1.1, 1.0 Hz, 1 H), 7.37–7.39 (m, 3 H), 7.20 (d,
J = 8.0 Hz, 2 H), 5.02 (d, J = 7.4 Hz, 1 H), 4.01 (dd, J = 2.3, 1.4 Hz, 2 H),
3.46–3.51 (m, 1 H), 2.34 (s, 3 H), 2.10 (s, 3 H), 1.54–1.58 (m, 2 H),
1.27–1.30 (m, 2 H), 1.24 (d, J = 6.7 Hz, 2 H), 1.19–1.22 (m, 4 H), 0.85 (t,
J = 7.3 Hz, 3 H).
13C NMR (150 MHz, CDCl3):  = 158.4, 146.0, 140.8, 138.9, 132.4,
132.3, 131.4, 130.0, 128.9, 77.7, 57.1, 35.5, 34.6, 32.0, 28.2, 25.5, 24.4,
17.0, 15.5.
HRMS (ESI): m/z [M + H] calcd for C23H24ClN2O3S: 443.1196; found:
443.1191.
N-{1-(4-Chlorophenyl)-2-[(4-methylphenyl)sulfonamido]ethyl}-
1-phenylethan-1-imine Oxide (4g′) and N-{2-(4-Chlorophenyl)-2-
[(4-methylphenyl)sulfonamido]ethyl}-1-phenylethan-1-imine
Oxide (5g′)
HRMS (ESI): m/z [M + H] calcd for C23H33N2O3S: 417.2212; found:
417.2199.
White solid; yield: 34.6 mg (78%); mp 108–109 °C.
Funding Information
1H NMR (600 MHz, CDCl3):  = 7.53–7.55 (m, 4 H), 7.39–7.40 (m, 3 H),
7.34–7.36 (m, 1 H), 7.26–7.28 (d, J = 8.4 Hz, 1 H), 7.23 (s, 4 H), 7.17–
7.19 (d, J = 8.5 Hz, 1 H), 7.07–7.08 (d, J = 8.0 Hz, 2 H), 5.70–5.71 (d, J =
3.8 Hz, 1 H), 5.22–5.24 (dd, J = 4.2, 8.4 Hz, 0.2 H), 5.05–5.07 (dd, J =
4.2, 7.8 Hz, 0.2 H), 4.57–4.61 (m, 1 H), 4.16–4.19 (dd, J = 3.9, 4.0 Hz, 1
We appreciate gratefully the Natural Science Foundation of Shanxi
Province (No. 201601D011028) for financial support.
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–O

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X. Li et al.
Paper
Synthesis
Supporting Information
(9) (a) Katahara, S.; Kobayashi, S.; Fujita, K.; Matsumoto, T.; Sato, T.;
Chida, N. J. Am. Chem. Soc. 2016, 138, 5246. (b) Moran, J.;
Pfeiffer, J. Y.; Gorelsky, S. I.; Beauchemin, A. M. Org. Lett. 2009,
11, 1895. (c) Nguyen, T. B.; Martel, A.; Dhal, R.; Dujardin, G. Org.
Lett. 2008, 10, 4493. (d) Li, Z.; Zhao, J.; Sun, B.; Zhou, T.; Liu, M.;
Liu, S.; Zhang, M.; Zhang, Q. J. Am. Chem. Soc. 2017, 139, 11702.
(10) Selected reviews: (a) Ha, H.-J.; Jung, J.-H.; Lee, W. K. Asian J. Org.
Chem. 2014, 3, 1020. (b) Pineschi, M. Synlett 2014, 25, 1817.
(c) Stanković, S.; D’hooghe, M.; Catak, S.; Eum, H.; Waroquier,
M.; Van Speybroeck, V.; De Kimpe, N.; Ha, H.-J. Chem. Soc. Rev.
2012, 41, 643.
(11) Selected examples: (a) Arai, K.; Lucarini, S.; Salter, M. M.; Ohta,
K.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2007, 129,
8103. (b) Chai, Z.; Yang, P.-J.; Zhang, H.; Wang, S.; Yang, G.
Angew. Chem. Int. Ed. 2017, 56, 650. (c) Peruncheralathan, S.;
Teller, H.; Schneider, C. Angew. Chem. Int. Ed. 2009, 48, 4849.
(12) Selected examples: (a) Wu, B.; Gallucci, J. C.; Parquette, J. R.;
RajanBabu, T. V. Angew. Chem. Int. Ed. 2009, 48, 1126.
(b) Fukuta, Y.; Mita, T.; Fukuda, N.; Kanai, M.; Shibasaki, M.
J. Am. Chem. Soc. 2006, 128, 6312. (c) Schneider, C. Angew. Chem.
Int. Ed. 2009, 48, 2082. (d) Chung, B. K. W.; White, C. J.; Scully, C.
C. G.; Yudin, A. K. Chem. Sci. 2016, 7, 6662.
(13) (a) Liew, S. K.; Holownia, A.; Diaz, D. B.; Cistrone, P. A.; Dawson,
P. E.; Yudin, A. K. Chem. Commun. 2017, 53, 11237. For a review
see: (b) Li, J.; Hu, Y.; Zhang, D.; Liu, Q.; Dong, Y.; Liu, H. Adv.
Synth. Catal. 2017, 359, 710.
(14) Selected examples: (a) Minakata, S.; Okumura, S.; Nagamachi,
T.; Takeda, Y. Org. Lett. 2011, 13, 2966. (b) Yoshimura, A.;
Nguyen, K. C.; Klasen, S. C.; Saito, A.; Nemykin, V. N.; Zhdankin,
V. V. Chem. Commun. 2015, 51, 7835. (c) Yao, T.; Ren, B.; Wang,
B.; Zhao, Y. Org. Lett. 2017, 19, 3135.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690186.
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