Highly Efficient Synthesis of N -Sulfonylamidines via Silver-Catalyzed or Metal-Free Thermally Promoted Denitrogenative Amination of N -Sulfonyl-1,2,3-triazoles

Article abstract of DOI:10.1055/s-0036-1588103

A highly efficient synthesis of N-sulfonylamidines from N-sulfonyl-1,2,3-triazoles and amines is reported. This transformation undergoes silver-catalyzed or metal-free thermally promoted denitrogenation of N-sulfonyl-1,2,3-triazoles to afford N-sulfonylketenimine intermediates and subsequent nucleophilic addition with amines. The amine plays dual roles as base and nucleophile.

Full text of DOI:10.1055/s-0036-1588103

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–I
paper
A
Y. Feng et al.
Paper
Synthesis
Highly Efficient Synthesis of N-Sulfonylamidines via Silver-
Catalyzed or Metal-Free Thermally Promoted Denitrogenative
Amination of N-Sulfonyl-1,2,3-triazoles
Yue Fenga
Wanjia Zhoua
Ge Sunb
Peiqiu Liaoa
Xihe Bi*a,c
Xingqi Li*a
NTs
NTs
Ts
N
H
NR1R2R3
N
N
R
R
N
N
R2
R1
R
toluene, N2
120 °C
Ag2CO3 (10 mol%)
toluene, N2, 80 °C
N
13 examples
up to 87%
12 examples
up to 94%
a Department of Chemistry, Northeast Normal University,
5268 Renmin Street, 130024 Changchun, P. R. of China
lixq653@nenu.edu.cn
b College of Pharmacy, Qiqihar Medical University, 333
Bukui Street, 161006 Qiqihar, P. R. of China
c State Key Laboratory of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, P. R. of China
Received: 21.09.2016
Accepted after revision: 27.10.2016
Published online: 28.11.2016
erated N-sulfonylketenimine intermediate. However, the at-
tempts of Chang et al. to prepare N-sulfonylamidines using
N-sulfonyltriazoles as starting materials were unsuccessful
due to the stability of N-sulfonyltriazole under their em-
ployed conditions. It is well known that the relatively stable
metalated ketenimine can be formed when N-sulfonyltri-
azole is treated with a strong base, such as n-BuLi at low
temperature.7 The only example of N-sulfonylamidine for-
mation from metalated ketenimine, lithiated ketenimine,
and diisopropylamine was reported by Chang et al. (Scheme
1, b).5c However, the use of strong base limits the scope of
N-sulfonyltriazoles. Recently, Li et al. reported the synthesis
of N-sulfonylamidines from N-sulfonyl-1,2,3-triazoles and
nitrosobenzene derivatives under rhodium-catalyzed con-
ditions via α-imino rhodium carbene intermediates.8
Inspired by Chang’s and Li’s work and interested in de-
veloping a new route to N-sulfonylamidines, we envisioned
that N-sulfonyltriazoles may serve as the precursors of N-
sulfonylketenimines under appropriate reaction condition,
followed by the nucleophilic addition of amines to the in
situ generated N-sulfonylketenimines to form N-sulfonyl-
amidines. Herein, we report a highly efficient method for
the synthesis of N-sulfonylamidines via silver-catalyzed or
metal-free thermally promoted denitrogenative amination
of N-sulfonyl-1,2,3-triazoles (Scheme 1, c).
DOI: 10.1055/s-0036-1588103; Art ID: ss-2016-h0659-op
Abstract A highly efficient synthesis of N-sulfonylamidines from N-sul-
fonyl-1,2,3-triazoles and amines is reported. This transformation under-
goes silver-catalyzed or metal-free thermally promoted denitrogena-
tion of N-sulfonyl-1,2,3-triazoles to afford N-sulfonylketenimine
intermediates and subsequent nucleophilic addition with amines. The
amine plays dual roles as base and nucleophile.
Key words amination, denitrogenation, N-sulfonylamidines, N-sulfo-
nyl-1,2,3-triazoles, nucleophilic addition
N-Sulfonylamidines are gaining increasing attention in
the field of synthetic and medicinal chemistry due to their
unique structure and fascinating chemical properties. They
are not only the essential part of a wide range of natural
products and biologically active molecules,1 but also serve
as useful intermediates for the synthesis of a variety of het-
erocyclic compounds and efficient coordinating ligands.2
A variety of methods are known for the synthesis of N-
sulfonylamidines.3 With the requirement of more efficient
synthesis of N-sulfonylamidine derivatives, a pioneering
copper-catalyzed three-component coupling of a terminal
alkyne, sulfonyl azide, and secondary amine to construct N-
sulfonylamidine was reported by Chang et al. (Scheme 1,
a).4 This reaction has received much attention due to the
tolerance of various functional groups. Subsequently, Chang
and several other groups applied this strategy to synthesize
amidines and its derivatives,5 poly(N-sulfonylamidine)s6
and aminonaphthoquinone-sulfonylamidine conjugates.1d
Mechanistically, the formation of N-sulfonylamidine takes
place by the nucleophilic attack of amine to the in situ gen-
Initially, our exploratory studies commenced with 4-
phenyl-1-tosyl-1H-1,2,3-triazole (1a), which was prepared
from the copper-catalyzed ethynylbenzene/4-methylben-
zenesulfonyl azide cycloaddition9 and diisopropylamine
(2a). Based on our continuous endeavor in developing sil-
ver-catalyzed organic reaction,10 1a was reacted with 1.5
equivalents of 2a in the presence of 10 mol% AgNO3 relative
to 1a using toluene as solvent at 80 °C for 12 hours under
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

B
Y. Feng et al.
Paper
Synthesis
Chang's work:
R1
H
NSO2R2
SO2R2
Cu
N
R3
R4
N
[Cu]
SO2R2
N
R1
R4
(a)
(b)
[Cu]
N
C
N
N
+
– N2
R1
R3
R2SO2N3
R1
SO2Ph
NSO2Ph
N
N
Li
SO2Ph
HN(i-Pr)2
N
n-BuLi
C
N
Ph
0 to 25 °C
THF, 2 h
N(i-Pr)2
THF, 0 °C
Ph
80% yield
Ph
this work:
R
Ts
N
HN(i-Pr)2
H2C
HN(i-Pr)2
Ts
C
N(i-Pr)2
Ag2CO3, 80 °C
N
H
R
Ts
N
(c)
C
N
– N2
N
R
R
120 °C
CH2
NR1R2R3
R1R2N
C
NR1R2R3
N
Ts
Scheme 1 Synthesis of N-sulfonylamidines via N-sulfonylketenimine intermediates
nitrogen atmosphere. To our delight, the N-sulfonylamidine,
N,N-diisopropyl-2-phenyl-N′-tosylacetimidamide (3a), was
obtained in 52% yield. The structure of 3a was unambigu-
ously confirmed by the X-ray single crystal diffraction
(Scheme 2)11 and spectral and analytical data. This prompt-
ed us to undertake further investigation, and it was finally
found that the reaction of 1a with 2a in toluene in the pres-
ence of 10 mol% Ag2CO3 relative to 1a under nitrogen atmo-
sphere could afford 3a in 86% yield (Scheme 2).
was the best catalyst in term of the yield. Pd(PPh3)4 and
Pd(OAc)2 were found to be poor catalysts for this reaction
(entries 11, 12). In contrast, with CuI, CuOAc, K2CO3, and
Li2CO3, respectively, as catalyst under similar conditions,
the reaction of 1a with 2a gave no expected product (en-
tries 7–10). When the loading of Ag2CO3 was decreased to 5
mol%, the yield of product decreased to 15% (entry 5). The
control experiment in the absence of Ag2CO3 was also car-
ried out and no expected product was detected (entry 6).
The effects of reaction temperatures and different solve
nts on the reaction of 1a with 2a using 10 mol% Ag2CO3 as
catalyst were also studied. When the reaction was per-
formed at room temperature and 40 °C, respectively, no ex-
pected product was obtained (Table 1, entries 13, 14). Upon
further raising the reaction temperature to 120 °C, the de-
sired product was isolated in 43% yield (entry 15). The
cause of low yield at 120 °C is probably due to the low boil-
ing point of diisopropylamine. Different solvents were sur-
veyed to ascertain the effect of the reaction medium on the
yield. Among the solvents studied, the reaction worked
most effectively in toluene. Inferior results were observed
when the reaction was performed in other solvents, such as
DCE, 1,4-dioxane, DMSO, and EtOH (entries 16–19).
After determining the optimized reaction conditions,
we investigated the scope of the reaction for many different
N-sulfonyltriazoles. As shown in Table 2, a variety of the N-
sulfonyltriazoles with various substituents at the C4 posi-
tion can be subjected to this silver-catalyzed denitrogena-
tive amination reaction, giving the corresponding products
in moderate to excellent yields. Aside from these common
electron-rich and -deficient (hetero)aryl and alkyl groups
(Table 2, entries 1–8, 10, 12), several highly reactive func-
tional groups, including alkenyl, and cyclopropyl moieties
Scheme 2 Silver-catalyzed synthesis of 3a from 1a and 2a
To evaluate the catalytic efficiency of Ag2CO3, The reac-
tion of 1a with 2a was investigated under different reaction
conditions including catalysts, reaction temperatures, and
solvents. The results are summarized in Table 1. It is notice-
able that several catalysts, namely, AgOTf, AgNO3, Ag2O, CuI,
CuOAc, Pd(PPh3)4, Pd(OAc)2, K2CO3, and Li2CO3 were tried,
but only silver salt was found to be effective in this reaction
(Table 1 entries 1–4). Among the Ag salts screened, Ag2CO3
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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Y. Feng et al.
Paper
Synthesis
Table 1 Optimization of Reaction Conditionsa
pylamine could play dual roles as base and nucleophile.
These postulates need to be demonstrated through further
experimental results.
Ts
N
NTs
N
HN
catalyst
N
N
Table 2 Silver-Catalyzed Synthesis of N,N-Diisopropyl-N-sulfonylami-
dines
solvent, N2, temp (°C)
2a
1a
3a
NTs
Ts
Ag2CO3 (10 mol%)
toluene, N2, 80 °C
N
N
R
H2N
Entry
Catalyst (mol%)
Temp (°C)
Solvent
Yield (%)b
N
R
N
1
2
AgNO3 (10)
AgOTf (10)
Ag2O (10)
80
80
80
80
80
80
80
80
80
80
80
80
r.t.
40
120
80
80
80
80
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
52
2a
3b–m
46
3
73
Entry N-Sulfonyltriazole
Product
Yield
(%)a
4
Ag2CO3 (10)
Ag2CO3 (5)
–
86
5
15
NTs
6
N.D.
N.D.
N.D.
N.D.
N.D.
42
N
1
85
87
Ts
Ts
Ts
Ts
Ts
N
7
K2CO3 (10)
Li2CO3 (10)
CuI (10)
N
N
3b
8
O
9
O
F
NTs
10
11
12
13
14
15
16
17
18
19
CuOAc (10)
Pd(PPh3)4 (10)
Pd(OAc)2 (10)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
Ag2CO3 (10)
2
3
4
5
N
N
N
N
N
N
N
N
N
N
N
N
N
3c
37
F
N.D.
N.D.
43
NTs
N
77
76
76
3d
23
Cl
1,4-dioxane
DMSO
71
Cl
Br
NTs
6
N
EtOH
trace
a Reaction conditions: The mixture of 4-phenyl-1-tosyl-1H-1,2,3-triazole
(1a; 0.5 mmol), i-Pr2NH (0.75 mmol), and the catalyst in toluene (1 mL) was
stirred for 12 h under N2 atmosphere.
3e
Br
NTs
b Isolated yield; N.D. = not detected.
N
3f
(entries 9, 11), were found to be well tolerated. However,
when we attempted to further broaden the scope of
amines, this transformation was unsuccessful. For example,
with N-methylaniline (2b) instead of 2a, the expected N-
sulfonylamidine was not obtained and desulfonylated tri-
azole was generated via the nucleophilic substitution reac-
tion. We speculate that a competitive reaction between the
ring opening of N-sulfonyltriazole and the nucleophilic sub-
stitution reaction could be in existence, and the weak basic-
ity of 2b relative to 2a could cause the nucleophilic substi-
tution reaction. Although the reaction mechanism is not
completely understood at present, the synergistic effect of
Ag2CO3 and diisopropylamine probably promote the ring-
opening of N-sulfonyltriazole and accelerate the loss of ni-
trogen to form the N-sulfonylketenimine intermediate fol-
lowed by the nucleophilic addition of diisopropylamine to
the in situ generated N-sulfonylketenimine affording N,N-
diisopropyl-N-sulfonylamidine (Scheme 1, c). The diisopro-
N
N
N
N
Ts
6
7
8
79
82
75
NTs
3g
NTs
N
N
N
Ts
Ts
N
N
N
N
3h
S
NTs
S
N
N
N
3i
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

D
Y. Feng et al.
Paper
Synthesis
Table 3 (continued)
nucleophilic addition with amines. To the best of our
knowledge, N-sulfonyl-1,2,3-triazoles as precursors of N-
sulfonylketenimines have been little investigated and the
use of N-sulfonyl-1,2,3-triazoles as starting material for the
synthesis of N-sulfonylamidines is underdeveloped so far.
Additional studies directed at better understanding the
mechanism of this process and at further exploring its utili-
ty are currently underway and will be reported in due
course.
Entry N-Sulfonyltriazole
Product
Yield
(%)a
NTs
N
N
N
Ts
N
9
61
3j
NTs
N
N
N
10
83
51
N
Ts
Table 3 Metal-Free Thermally Promoted Synthesis of N-Sulfonylami-
dines
3k
NTs
NTs
Ts
N
Ts
Ph
N
N
R1
N
120 °C
N
R2
11
NR1R2R3
Ph
N
N
N
toluene, N2
3l
2b–m
4b–m
1a
Entry
1
Amine
Product
Yield (%)a
NTs
12
86
NTs
N
Ts
N
Ph
92
N
N
N
N
H
3m
4b
a Isolated yield.
NTs
Ph
2
3
4
89
92
93
N
For broadening the scope of amines, we further opti-
mized the reaction conditions based on the above condi-
tions. In order to suppress the nucleophilic substitution re-
action and promote the ring-opening of N-sulfonyltriazole
to form the corresponding N-sulfonylketenimine interme-
diate, the reaction temperature was raised to 120 °C. The
formation of N-sulfonylketenimine intermediates from N-
sulfonyl-1,2,3-triazoles under thermal conditions has been
demonstrated by Shi and co-workers.12 To our delight, the
N-sulfonylamidine, N-methyl-N,2-diphenyl-N′-tosylacetim-
idamide (4b), was obtained in 92% yield. To our surprise, 4b
was also obtained in the same yield in the absence of
Ag2CO3 (Table 3, entry 1). With the further optimized con-
ditions in hand, an array of amines including primary, sec-
ondary, and tertiary amines were screened in the absence
of Ag2CO3 at 120 °C using toluene as solvent. As shown in
Table 3, a range of N-sulfonylamindines was generated in
excellent yield. However, we found that desulfonylated tri-
azole was generated again when 1a was reacted with ani-
line. This result implies that the steric hindrance effect of
the amine needs to be considered for the formation of N-
sulfonylketenimine intermediate; the bulky amines are in
favor of N-sulfonylketenimine formation under thermal
conditions.
N
H
4c
NTs
Ph
N
N
H
4d
NTs
Ph
N
N
H
4e
NTs
Ph
HN
N
5
6
94
93
4f
NTs
Ph
N
N
H
4g
NTs
Ph
H
N
N
In conclusion, we have developed a highly efficient
method to construct N-sulfonylamidines. This transforma-
tion undergoes silver-catalyzed or metal-free thermally
promoted denitrogenation of N-sulfonyl-1,2,3-triazoles to
afford N-sulfonylketenimine intermediates and subsequent
7
89
4h
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E
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Synthesis
13C NMR (125MHz, CDCl3): δ = 19.8, 21.4, 38.7, 48.0, 50.4, 126.2,
Table 3 (continued)
126.7, 128.0, 128.8, 129.0, 134.9, 141.5, 141.5, 163.4.
HRMS (ESI): m/z calcd for C21H29N2O2S [M + H]+: 373.1951; found:
373.1950.
Entry
8
Amine
Product
Yield (%)a
NTs
Ph
H
N
N
N,N-Diisopropyl-2-(p-tolyl)-N′-tosylacetimidamide (3b)
90
White solid; yield: 164 mg (85%); mp 165–166 °C.
1H NMR (500 MHz, CDCl3): δ = 0.88 (d, J = 6.5 Hz, 6 H), 1.39 (d, J = 6.5
Hz, 6 H), 2.30 (s, 3 H), 2.39 (s, 3 H), 3.41–3.45 (m, 1 H), 3.97–4.02 (m, 1
H), 4.35 (s, 2 H), 7.02–7.11 (m, 4 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.82 (d,
J = 7.5 Hz, 2 H).
4i
13C NMR (CDCl3, 125 MHz): δ = 19.8, 19.8, 21.0, 21.4, 38.3, 47.9, 50.3,
TsN
9
NH2
94
NH
NH
126.1, 127.7, 128.9, 129.4, 131.7, 136.2, 141.4, 163.6.
HRMS (ESI): m/z calcd for C22H29N2O2S [M + H]+: 387.2107; found:
387.2111.
Ph
4j
Ph
NH2
N,N-Diisopropyl-2-(4-methoxyphenyl)-N′-tosylacetimidamide (3c)
TsN
10
11
12
90
90
89
White solid; yield: 175 mg (87%); mp 111–112 °C.
1H NMR (400 MHz, CDCl3): δ = 0.89 (d, J = 6.4 Hz, 6 H), 1.38 (d, J = 6.8
Hz, 6 H), 2.39 (s, 3 H), 3.41–3.45 (m, 1 H), 3.78 (s, 3 H), 3.99–4.05 (m, 1
H), 4.32 (s, 2 H), 6.82 (d, J = 8.4 Hz, 2 H), 7.12 (d, J = 8.4 Hz, 2 H), 7.23
(d, J = 8.0 Hz, 2 H), 7.83 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 19.75, 19.82, 21.4, 37.9, 47.9, 50.3,
55.2, 114.2, 126.1, 126.8, 129.0, 129.0, 141.5, 158.3, 163.7.
4k
NTs
Ph
4l
N
N
HRMS (ESI): m/z calcd for C22H29N2O3S [M + H]+: 402.5511; found:
402.5513.
NTs
Ph
N
2-(4-Fluorophenyl)-N,N-diisopropyl-N′-tosylacetimidamide (3d)
N
White solid; yield: 150 mg (77%); mp 150–151 °C.
4m
1H NMR (500 MHz, CDCl3): δ = 0.90 (d, J = 8.0 Hz, 6 H), 1.37 (d, J = 8.5
Hz, 6 H), 2.40 (s, 3 H), 3.43–3.46 (m, 1 H), 3.93–4.00 (m, 1 H), 4.37 (s, 2
H), 6.97–7.01 (m, 2 H), 7.18–7.21 (m, 2 H), 7.24 (d, J = 8.0 Hz, 2 H),
7.82 (d, J = 8.0 Hz, 2 H).
a Isolated yield.
13C NMR (CDCl3, 125 MHz): δ = 19.7, 19.8, 21.4, 37.9, 48.0, 50.3, 115.5,
115.7, 126.1, 129.0, 129.48, 129.54, 141.3, 141.6, 160.6, 162.6, 163.0.
HRMS (ESI): m/z calcd for C21H26FN2O2S [M + H]+: 390.5111; found:
390.5113.
All reagents were purchased from commercial sources and used with-
out treatment, unless otherwise indicated. The products were puri-
fied by column chromatography over silica gel. Melting points were
1
determined in open capillaries and are uncorrected. H NMR spectra
were recorded at 25 °C on a Varian 500 MHz or 400 MHz and 13C NMR
spectra were recorded at 25 °C on a Varian 125 MHz, respectively, us-
ing TMS as internal standard. Mass spectra were recorded on Bruker
AutoflexIII Smartbeam MS-spectrometer. High-resolution mass spec-
tra (HRMS) were recorded on Bruck microTof by using ESI method.
2-(4-Chlorophenyl)-N,N-diisopropyl-N′-tosylacetimidamide (3e)
White solid; yield: 155 mg (76%); mp 155–156 °C.
1H NMR (500 MHz, CDCl3): δ = 0.91 (d, J = 6.0 Hz, 6 H), 1.38 (d, J = 6.5
Hz, 6 H), 2.40 (s, 3 H), 3.43–3.49 (m, 1 H), 3.93–3.95 (m, 1 H), 4.37 (s, 2
H), 7.15 (d, J = 7.5 Hz, 2 H), 7.22–7.27 (m, 4 H), 7.81 (d, J = 7.5 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 19.7, 19.9, 21.4, 38.0, 48.1, 50.4, 126.1,
128.9, 129.0, 129.3, 132.6, 133.4, 141.2, 141.7, 162.7.
Silver-Catalyzed Denitrogenative Amination of N-Sulfonyl-1,2,3-
triazoles 1a–m with Diisopropylamine; N,N-Diisopropyl-2-phenyl-
N′-tosylacetimidamide (3a); Typical Procedure
HRMS (ESI): m/z calcd for C21H26ClN2O2S [M + H]+: 406.9712; found:
406.9716.
A mixture of i-Pr2NH (76 mg, 0.75 mmol), 4-phenyl-1-tosyl-1H-1,2,3-
triazole (1a; 150 mg, 0.5 mmol) and Ag2CO3 (13.8 mg, 0.05 mmol) in
toluene (1 mL) was stirred at 80 °C under N2 for 12 h until the sub-
strates had disappeared. The reaction was quenched with H2O. The
reaction mixture was filtered to remove insoluble substance and the
filterate was extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were concentrated in vacuo and the residue was purified by
flash chromatography on silica gel to give 3a as a white solid; yield:
160 mg (86%); mp 147.5–148.5 °C.
2-(4-Bromophenyl)-N,N-diisopropyl-N′-tosylacetimidamide (3f)
White solid; yield: 171 mg (76%); mp 154–155 °C.
1H NMR (500 MHz, CDCl3): δ = 0.91 (d, J = 6.5 Hz, 6 H), 1.38 (d, J = 6.5
Hz, 6 H), 2.40 (s, 3 H), 3.42–3.49 (m, 1 H), 3.91–3.96 (m, 1 H), 4.36 (s, 2
H), 7.09 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.41 (d, J = 8.0 Hz,
2 H), 7.80 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 19.7, 19.9, 21.4, 38.0, 48.1, 50.4, 120.7,
126.1, 129.0, 129.6, 131.9, 133.9, 141.2, 141.7, 162.6.
1H NMR (500 MHz, CDCl3): δ = 0.87 (d, J = 6.5 Hz, 6 H), 1.39 (d, J = 6.5
Hz, 6 H), 2.34 (s, 3 H), 3.44–3.48 (m, 1 H), 3.96–4.02 (m, 1 H), 4.41 (s, 2
H), 7.11–7.31 (m, 7 H), 7.81 (d, J = 8.0 Hz, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

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Y. Feng et al.
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HRMS (ESI): m/z calcd for C21H26BrN2O2S [M + H]+: 451.4221; found:
13C NMR (CDCl3, 125 MHz): δ = 14.1, 20.0, 20.7, 21.4, 22.6, 27.3, 28.8,
451.4225.
29.8, 31.7, 32.8, 47.8, 49.8, 126.0, 129.0, 141.3, 141.9.
HRMS (ESI): m/z calcd for C21H35N2O2S [M + H]+: 376.5614; found:
376.5618.
N,N-Diisopropyl-2-(naphthalen-2-yl)-N′-tosylacetimidamide (3g)
White solid; yield: 167 mg (79%); mp 160–161 °C.
1H NMR (500 MHz, CDCl3): δ = 0.86 (d, J = 6.5 Hz, 6 H), 0.86 (d, J = 7.0
Hz, 6 H) 2.28 (s, 3 H), 3.45–3.51 (m, 1 H), 4.05–4.09 (m, 1 H), 4.56 (s, 2
H), 7.15 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 1 H), 7.43–7.47 (m, 3 H),
7.68 (d, J = 8.0 Hz, 1 H), 7.76–7.82 (m, 4 H).
13C NMR (CDCl3, 125 MHz): δ = 19.9, 21.3, 38.3, 48.1, 50.4, 125.7,
126.1, 126.1, 126.2, 126.3, 127.5, 127.6, 128.5, 128.9, 132.1, 132.2,
133.4, 141.3, 141.6, 163.4.
2-Cyclopropyl-N,N-diisopropyl-N′-tosylacetimidamide (3l)
White solid; yield: 86 mg (51%); mp 94–95 °C.
1H NMR (400 MHz, CDCl3): δ = 0.51–0.55 (m, 2 H), 0.56–0.61 (m, 2 H),
0.91–0.96 (m, 1 H), 1.24 (d, J = 6.4 Hz, 6 H), 1.32 (d, J = 6.8 Hz, 6 H),
2.39 (s, 3 H), 2.99 (d, J = 6.4 Hz, 2 H), 3.48–3.53 (m, 1 H), 4.20–4.25 (m,
1 H), 7.24 (d, J = 8.0 Hz, 2 H) 7.80 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 5.2, 8.6, 20.0, 20.6, 21.4, 35.6, 47.8,
50.3, 126.0, 128.9, 141.3, 141.8, 165.2.
HRMS (ESI): m/z calcd for C25H29N2O2S [M + H]+: 422.5812; found:
422.5815.
HRMS (ESI): m/z calcd for C18H27N2O2S [M + H]+: 336.4902; found:
336.4908.
N,N-Diisopropyl-2-(pyridin-3-yl)-N′-tosylacetimidamide (3h)
Yellow solid; yield: 153 mg (82%); mp 146.6–147.7 °C.
2-([1,1′-Biphenyl]-4-yl)-N,N-diisopropyl-N′-tosylacetimidamide
1H NMR (500 MHz, CDCl3): δ = 0.92 (d, J = 7.5 Hz, 6 H), 1.38 (d, J = 7.5
Hz, 6 H), 2.40 (s, 3 H), 3.45–3.49 (m, 1 H), 3.90–3.96 (m, 1 H), 4.42 (s, 1
H), 7.24–7.28 (m, 3 H), 7.66 (d, J = 7.5 Hz, 1 H), 7.82 (d, J = 7.5 Hz, 2 H),
8.46 (s, 1 H), 8.50 (d, J = 4.0 Hz, 1 H).
13C NMR (CDCl3, 125 MHz): δ = 19.7, 19.9, 21.4, 36.0, 48.2, 50.4, 123.7,
126.1, 129.1, 130.8, 135.5, 141.1, 141.8, 148.3, 149.2, 162.0.
(3m)
White solid; yield: 193 mg (86%); mp 157–159 °C.
1H NMR (500 MHz, CDCl3): δ = 0.92 (d, J = 5.0 Hz, 6 H), 1.41 (d, J = 6.0
Hz, 6 H), 2.38 (s, 3 H), 3.45–3.50 (m, 1 H), 4.02–4.06 (m, 1 H), 4.45 (s, 2
H), 7.22–7.25 (m, 4 H), 7.32–7.36 (m, 1 H), 7.41–7.45 (m, 2 H), 7.53 (d,
J = 7.0 Hz, 2 H), 7.57 (d, J = 6.5 Hz, 2 H), 7.84 (d, J = 6.5 Hz, 2 H).
HRMS (ESI): m/z calcd for C20H26N3O2S [M + H]+: 373.5114; found:
373.5118.
13C NMR (CDCl3, 125 MHz): δ = 19.8, 19.9, 21.4, 38.3, 48.0, 50.4, 126.2,
126.9, 127.3, 127.4, 128.3, 128.7, 129.0, 133.9, 139.5, 140.5, 141.4,
141.6, 163.3.
HRMS (ESI): m/z calcd for C27H31N2O2S [M + H]+: 448.6217; found:
N,N-Diisopropyl-2-(thiophen-3-yl)-N′-tosylacetimidamide (3i)
448.6221.
White solid; yield: 147 mg (75%); mp 149.1–150.1 °C.
1H NMR (400 MHz, CDCl3): δ = 0.99 (d, J = 6.8 Hz, 6 H), 1.37 (d, J = 6.8
Hz, 6 H), 2.39 (s, 3 H), 3.46–3.50 (m, 1 H), 4.13–4.16 (m, 1 H), 4.53 (s, 2
H), 6.87 (s, 1 H), 6.89–6.91 (m, 1 H), 7.16 (d, J = 4.8 Hz, 1 H), 7.23 (d,
J = 8.0 Hz, 2 H), 7.81 (d, J = 8.0 Hz, 2 H).
Metal-Free Thermally Promoted Denitrogenative Amination of 4-
Phenyl-1-tosyl-1H-1,2,3-triazole (1a) with Various Amines;
N,N-Dicyclohexyl-2-phenyl-N′-tosylacetimidamide (4h); Typical
Procedure
13C NMR (CDCl3, 125 MHz): δ = 19.7, 20.0, 21.4, 32.9, 48.2, 50.5, 124.4,
A mixture of 4-phenyl-1-tosyl-1H-1,2,3-triazole (1a; 150 mg, 0.5
mmol) and dicyclohexylamine (0.75 mmol) in toluene (1 mL) was
stirred under N2 atmosphere for 12 h at 120 °C until the substrates
had disappeared. The reaction was quenched with H2O and the mix-
ture was extracted by CH2Cl2 (3 × 20 mL). The combined organic lay-
ers were concentrated in vacuo and the residue was purified by flash
chromatography on silica gel to give 4h as a white solid; yield: 201
mg (89%); mp 157–158 °C.
126.2, 127.0, 129.0, 136.1, 141.3, 141.6, 162.0.
HRMS (ESI): m/z calcd for C19H25N2O2S2 [M + H]+: 378.5521; found:
378.5525.
2-(Cyclohex-1-en-1-yl)-N,N-diisopropyl-N′-tosylacetimidamide
(3j)
White solid; yield: 115 mg (61%); mp 98–99 °C.
1H NMR (500 MHz, CDCl3): δ = 1.14 (d, J = 6.5 Hz, 6 H), 1.40 (d, J = 6.5
Hz, 6 H), 1.47–1.51 (m, 2 H), 1.54–1.59 (m, 2 H), 1.84–1.90 (m, 2 H),
1.91–1.97 (m, 2 H), 2.38 (s, 3 H), 3.47–3.53 (m, 1 H), 3.57 (s, 2 H),
3.93–3.95 (m, 1 H), 5.21 (t, J = 5.5 Hz, 1 H), 7.22 (d, J = 7.5 Hz, 2 H),
7.78 (d, J = 7.5 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 20.0, 20.2, 21.4, 21.9, 22.6, 25.1, 28.5,
39.7, 48.0, 50.2, 123.3, 126.2, 128.9, 131.1, 141.3, 141.6, 163.8.
1H NMR (500 MHz, CDCl3): δ = 0.87–0.94 (m, 4 H), 1.08–1.15 (m, 4 H),
1.27–1.36 (m, 4 H), 1.49–1.53 (m, 2 H), 1.57–1.65 (m, 2 H), 1.66–1.72
(m, 2 H), 2.41 (s, 3 H), 2.58–2.63 (m, 2 H), 2.92–2.96 (m, 1 H), 3.54–
3.59 (m, 1 H), 4.40 (s, 2 H), 7.19–7.30 (m, 8 H), 7.86 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 21.4, 24.9, 25.2, 25.5, 26.3, 28.5, 30.2,
39.4, 58.6, 59.3, 126.2, 126.7, 128.2, 128.7, 128.9, 135.3, 141.5, 141.6,
163.6.
HRMS (ESI): m/z calcd for C21H31N2O2S [M + H]+: 484.1141, found:
HRMS (ESI): m/z calcd for C27H35N2O2S [M + H]+: 452.6511; found:
484.1145.
452.6515.
N,N-Diisopropyl-N′-tosyloctanimidamide (3k)
N-Methyl-N,2-diphenyl-N′-tosylacetimidamide (4b)
White solid; yield: 158 mg (83%); mp 113–114 °C.
White solid; yield: 174 mg (92%); mp 131.5–133.5 °C.
1H NMR (400 MHz, CDCl3): δ = 0.88–0.91 (m, 3 H), 1.24 (d, J = 6.5 Hz, 6
H), 1.26–1.30 (m, 6 H), 1.31 (d, J = 6.5 Hz, 6 H), 1.38–1.42 (m, 2 H),
1.57–1.63 (m, 2 H), 2.40 (s, 3 H), 2.86–2.89 (m, 2 H), 3.47–3.52 (m, 1
H), 4.00–4.06 (m, 1 H), 7.25 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ = 2.40 (s, 3 H), 3.32 (s, 3 H), 4.24 (s, 2 H),
6.76–6.81 (m, 4 H), 7.03–7.09 (m, 3 H), 7.19–7.28 (m, 5 H), 7.87 (d,
J = 8.0 Hz, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

G
Y. Feng et al.
Paper
Synthesis
13C NMR (CDCl3, 125 MHz): δ = 21.4, 37.6, 41.1, 126.3, 126.4, 127.2,
128.1, 128.3, 129.0, 129.4, 134.6, 141.0, 142.0, 142.5, 144.6, 166.3.
HRMS (ESI): m/z calcd for C22H21N2O2S [M + H]+: 378.4912; found:
378.4915.
1H NMR (500 MHz, CDCl3): δ = 0.77–0.80 (t, J = 7.5 Hz, 3 H), 1.18–1.22
(m, 2 H), 1.45–1.50 (m, 2 H), 2.38 (s, 3 H), 3.70 (t, J = 7.5 Hz, 2 H), 4.17
(s, 2 H), 6.70–6.78 (m, 4 H), 7.03–7.07 (m, 3 H), 7.17 (t, J = 7.5 Hz, 2 H),
7.23–7.25 (m, 3 H), 7.84 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 13.6, 19.9, 21.4, 28.7, 38.0, 52.7, 126.3,
126.3, 128.1, 128.1, 128.3, 129.0, 129.3, 134.8, 141.2, 141.2, 141.9,
165.7.
N-Methyl-2-phenyl-N-(m-tolyl)-N′-tosylacetimidamide (4c)
White solid; yield: 175 mg (89%); mp 120–121 °C.
HRMS (ESI): m/z calcd for C25H27N2O2S [M + H]+: 420.5710; found:
420.5713.
1H NMR (500 MHz, CDCl3): δ = 2.15 (s, 3 H), 2.41 (s, 3 H), 3.31 (s, 3 H),
4.22 (s, 2 H), 6.49 (s, 1 H), 6.67 (d, J = 7.5 Hz, 1 H), 6.78 (d, J = 6.0 Hz, 2
H), 7.06–7.14 (m, 5 H), 7.22–7.28 (m, 2 H), 7.88 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 21.0, 21.4, 37.8, 41.0, 124.0, 126.3,
126.4, 128.1, 128.4, 129.1, 129.2, 134.9, 139.6, 141.1, 142.0, 142.4,
166.4.
N,N,2-Triphenyl-N′-tosylacetimidamide (4i)
White solid; yield: 198 mg (90%); mp 185–186 °C.
1H NMR (500 MHz, CDCl3): δ = 2.37 (s, 3 H), 4.46 (s, 2 H), 6.92–6.93
(m, 4 H), 7.14–7.16 (m, 6 H), 7.20–7.29 (m, 7 H), 7.60 (d, J = 8.0 Hz, 2
H).
13C NMR (CDCl3, 125 MHz): δ = 21.4, 38.4, 126.2, 126.6, 127.0, 128.4,
HRMS (ESI): m/z calcd for C23H23N2O2S [M + H]+: 392.5113; found:
392.5115.
128.5, 128.9, 129.2, 134.6, 140.5, 141.4, 142.0, 166.9.
HRMS (ESI): m/z calcd for C27H23N2O2S [M + H]+: 440.5613; found:
N-Methyl-2-phenyl-N-(o-tolyl)-N′-tosylacetimidamide (4d)
White solid; yield: 180 mg (92%); mp 122–123 °C.
440.5617.
1H NMR (500 MHz, CDCl3): δ = 1.67 (s, 3 H), 2.42 (s, 3 H), 3.22 (s, 3 H),
4.11 (d, J = 15.0 Hz, 1 H), 4.25 (d, J = 15.0 Hz, 1 H), 6.75 (d, J = 7.0 Hz, 2
H), 6.83 (d, J = 8.0 Hz, 1 H), 7.06–7.11 (m, 5 H), 7.21–7.28 (m, 3 H),
7.91 (d, J = 7.5 Hz, 2 H).
2-Phenyl-N′-tosyl-N-tritylacetimidamide (4j)
White solid; yield: 249 mg (94%); mp 145–146 °C.
13C NMR (CDCl3, 125 MHz): δ = 16.7, 21.4, 37.7, 39.8, 126.4, 126.6,
127.0, 127.8, 128.1, 128.9, 129.0, 129.1, 131.4, 133.9, 135.9, 141.15,
141.21, 142.0, 166.5.
1H NMR (500 MHz, CDCl3): δ = 2.34 (s, 3 H), 4.40 (s, 2 H), 6.36 (s, 1 H),
6.90–6.96 (m, 6 H), 7.02 (d, J = 8.0 Hz, 2 H), 7.10–7.18 (m, 11 H), 7.29–
7.37 (m, 3 H), 7.39–7.42 (m, 2 H).
HRMS (ESI): m/z calcd for C23H23N2O2S [M + H]+: 392.5122; found:
392.5125.
13C NMR (CDCl3, 125 MHz): δ = 21.4, 40.8, 71.8, 126.1, 127.0, 127.7,
127.8, 127.9, 128.3, 128.47, 128.51, 128.6, 129.0, 129.6, 130.1, 133.4,
140.1, 141.5, 143.2, 163.8.
HRMS (ESI): m/z calcd for C34H29N2O2S [M + H]+: 530.6817; found:
N-Methyl-2-phenyl-N-(p-tolyl)-N′-tosylacetimidamide (4e)
5320.6821.
White solid; yield: 182 mg (93%); mp 121–122 °C.
1H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.40 (s, 3 H), 3.31 (s, 3 H),
4.23 (s, 2 H), 6.69 (d, J = 8.0 Hz, 2 H), 6.79 (d, J = 6.5 Hz, 2 H), 7.00 (d,
J = 8.0 Hz, 2 H), 7.06–7.11 (m, 3 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.85 (d,
J = 8.0 Hz, 2 H).
N-[(3s,5s,7s)-Adamantan-1-yl]-2-phenyl-N′-tosylacetimidamide
(4k)
White solid; yield: 190 mg (90%); mp 145–146 °C.
13C NMR (CDCl3, 125 MHz): δ = 21.0, 21.4, 37.5, 41.1, 126.3, 126.4,
126.8, 128.1, 128.3, 129.0, 130.0, 134.7, 138.4, 140.0, 141.0, 141.9,
166.4.
HRMS (ESI): m/z calcd for C23H23N2O2S [M + H]+: 392.5123; found:
392.5126.
1H NMR (500 MHz, CDCl3): δ = 1.52–1.61 (m, 6 H), 1.86 (d, J = 2.5 Hz, 6
H), 1.99 (s, 3 H), 2.42 (s, 3 H), 4.25 (s, 2 H), 4.88 (s, 1 H), 7.20 (d, J = 7.0
Hz, 2 H), 7.27 (d, J = 8.5 Hz, 2 H), 7.28–7.38 (m, 3 H), 7.86 (d, J = 8.5 Hz,
2 H).
13C NMR (CDCl3, 125 MHz): δ = 21.5, 29.2, 36.1, 40.5, 40.6, 54.0, 126.1,
128.0, 129.1, 129.3, 130.0, 133.5, 141.1, 141.8, 164.6.
HRMS (ESI): m/z calcd for C25H29N2O2S [M+ H]+: 422.5812; found:
N-Methyl-N-(naphthalen-1-yl)-2-phenyl-N′-tosylacetimidamide
(4f)
422.5816.
White solid; yield: 201 mg (94%); mp 157–158 °C.
1H NMR (500 MHz, CDCl3): δ = 2.43 (s, 3 H), 3.42 (s, 3 H), 3.82 (d,
J = 15.0 Hz, 1 H), 4.43 (d, J = 15.0 Hz, 1 H), 6.62 (d, J = 7.5 Hz, 2 H),
6.89–6.95 (m, 4 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 2 H),
7.38–7.41 (m, 2 H), 7.45–7.47 (m, 1 H), 7.80–7.85 (m, 2 H), 7.94 (d,
J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 21.5, 37.9, 40.8, 121.7, 125.2, 125.8,
126.3, 126.4, 126.6, 127.6, 128.0, 128.3, 128.4, 129.1, 129.2, 129.4,
134.3, 134.6, 138.5, 141.1, 142.1, 167.3.
N,N-Diethyl-2-phenyl-N′-tosylacetimidamide (4l)
White solid; yield: 155 mg (90%); mp 116–117 °C.
1H NMR (500 MHz, CDCl3): δ = 0.95 (t, J = 8.5 Hz, 3 H), 1.15 (t, J = 8.5
Hz, 3 H), 2.36 (s, 3 H), 3.20 (q, J = 8.5 Hz, 2 H), 3.50 (q, J = 8.5 Hz, 2 H),
4.38 (s, 2 H), 7.11 (d, J = 8.5 Hz, 2 H), 7.16–7.19 (m, 2 H), 7.21–7.25 (m,
2 H), 7.75 (d, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 11.9, 13.4, 21.4, 36.5, 43.2, 43.3, 126.2,
126.7, 127.8, 128.8, 128.9, 134.3, 141.2, 141.6, 164.5.
HRMS (ESI): m/z calcd for C26H23N2O2S [M + H]+: 428.5506; found:
428.5510.
HRMS (ESI): m/z calcd for C19H23N2O2S [M + H]+: 344.4712; found:
344.4715.
N-Butyl-N,2-diphenyl-N′-tosylacetimidamide (4g)
2-Phenyl-N,N-dipropyl-N′-tosylacetimidamide (4m)
White solid; yield: 196 mg (93%); mp 158–159 °C.
White solid; yield: 166 mg (89%); mp 118–119 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

H
Y. Feng et al.
Paper
Synthesis
1H NMR (500 MHz, CDCl3): δ = 0.75 (t, J = 7.0 Hz, 3 H), 0.85 (t, J = 7.0
Hz, 3 H), 1.34–1.40 (m, 2 H), 1.58–1.66 (m, 2 H), 2.37 (s, 3 H), 3.08 (t,
J = 7.5 Hz, 2 H), 3.39 (t, J = 7.5 Hz, 2 H), 4.39 (s, 2 H), 7.09–7.27 (m, 7
H), 7.77 (d, J = 7.5 Hz, 2 H).
13C NMR (CDCl3, 125 MHz): δ = 11.0, 11.4, 20.0, 21.4, 21.7, 36.8, 50.6,
50.8, 126.1, 126.7, 127.9, 128.8, 128.9, 134.4, 141.3, 141.6, 164.8.
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HRMS (ESI): m/z calcd for C21H27N2O2S [M + H]+: 372.5220; found:
372.5224.
Acknowledgment
This work was supported by the NSFC (21522202, 21372038), the
Ministry of Education of the People’s Republic of China (NCET-13-
0714), the Jilin Provincial Research Foundation for Basic Research
(20140519008JH), and Fundamental Research Funds for the Central
Universities (2412015BJ005).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588103.
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(11) Crystallographic data for 3a: space group P-1, a = 8.2090(6) Å,
b = 11.2709(9)
Å,
c = 12.4772(10)
Å,
α = 114.679(1)°,
β = 100.637(1)°, γ = 97.570(1)°, V = 1002.38(14) Å3, T = 293 K,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I

I
Y. Feng et al.
Paper
Synthesis
Z = 2. CCDC 1491766 contains the supplementary crystallo-
graphic data for compound 3a reported in this paper. These da
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/getstructures.
(12) (a) Jiang, Y.; Sun, R.; Wang, Q.; Tang, X. Y.; Shi, M. Chem.
Commun. 2015, 51, 16968. (b) Sun, R.; Jiang, Y.; Tang, X. Y.; Shi,
M. Chem. Eur. J. 2016, 22, 5727.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I