Sulfur-nitrogen and carbon-nitrogen bond formation by intermolecular imination and amidation without catalyst

Article abstract of DOI:10.1002/ejoc.201101463

Imination and amidation of sulfides, sulfoxides, and olefins using 4H-1,2,4-triazole-4-amine as a nitrogen source with PhI(OAc)₂ as an oxidant were achieved in moderate to high yields without the addition of a catalyst. The carbon-nitrogen and

Full text of DOI:10.1002/ejoc.201101463

FULL PAPER
DOI: 10.1002/ejoc.201101463
Sulfur–Nitrogen and Carbon–Nitrogen Bond Formation by Intermolecular
Imination and Amidation without Catalyst
Wen Bo Ma,[a] Sheng Nan Li,[a][‡] Zhong Hua Zhou,[a] Heng Shui Shen,[a] Xue Li,[a]
Qiu Sun,[a] Ling He,*[a] and Ying Xue*[b]
Keywords: Nitrogen heterocycles / Nitrenes / Reaction mechanisms / Insertion / C-N coupling / S-N coupling
Imination and amidation of sulfides, sulfoxides, and olefins
using 4H-1,2,4-triazole-4-amine as a nitrogen source with
PhI(OAc)2 as an oxidant were achieved in moderate to high
yields without the addition of a catalyst. The carbon–nitrogen
and sulfur–nitrogen bond forming reactivity is consistent
with a nitrene insertion mechanism in which the reactivity
generally increases with decreasing N–H bond dissociation
energy of the nitrogen source and increasing oxidation po-
tential of the oxidant.
the formation of nitrogen-containing compounds. Many
kinds of natural products, pharmaceutical compounds, and
insecticides are heterocyclic molecules that contain a poly-
azole unit.[14] It is thus important to synthesize polyazoles
derivatives through a convenient route with high yields.[14i]
With this aim in mind and because of our interest in synthe-
sizing potentially bioactive nitrogenous compounds, we de-
cided to study a new reaction system for the insertion reac-
tion to olefins, sulfoxides, and sulfides using 4-amino-4H-
1,2,4-triazole as nitrogen source. In this paper, we present
the first examples of the intermolecular imination of sulf-
ides and expand the intermolecular imination of sulfoxides
and the aziridination of alkenes through the direct use of
4-amino-4H-1,2,4-triazole as nitrogen source and PhI-
(OAc)2 as oxidant under mild conditions (Scheme 1).
Introduction
An efficient and convenient procedure for the direct for-
mation of sulfur–nitrogen and carbon–nitrogen bonds is a
powerful synthetic approach[1] to regioselective functionali-
zation of sulfides, sulfoxides,[2] and hydrocarbons.[3–5] Such
processes are increasingly attractive as synthetic routes to
aziridines,[3] amides, or imines, the derivatives of which have
been used as building blocks for the construction of hetero-
cyclic compounds and the preparation of chiral ligands.
Furthermore, such an approach can play a key role in the
preparation of many pharmacologically active com-
pounds.[5o,5p] Stereogenic sulfur atoms can be used as build-
ing blocks in bioactive molecules and pseudopeptides, chi-
ral auxiliaries for asymmetric synthesis, and ligands for
enantioselective metal catalysis.[6] Most synthetic methods,
however, depend upon the use of toxic and potentially ex-
plosive reagents such as hydrazoate[7] and O-mesitylene-
sulfonyl-hydroxylamine,[8] and typically require expensive
metal-based catalysts.[9–12] Amidation reactions involving
nitrogen-heterocycle-containing nitrogen sources are
rare.[13] Thus, establishing a reaction system that functions
in the absence of catalyst and using 4-amino-4H-1,2,4-tri-
azole as a nitrogen source should be significant for the de-
velopment of an efficient and convenient methodology for
[a] Key Laboratory of Drug-Targeting and Drug-Delivery Systems
of the Ministry of Education, Department of Medicinal
Chemistry, West China School of Pharmacy, Sichuan
University,
Scheme 1. Functionalization of olefins and sulfides using 4-amine-
4H-1,2,4-triazole as nitrogen source.
Chengdu, Sichuan 610041, P. R. of China
Fax: +86-28-85502940
E-mail: lhe2001@sina.com
[b] College of Chemistry, Sichuan University,
Chengdu 610064, P. R. of China
E-mail: yxue@scu.edu.cn
[‡] Joint first author.
With our interest in synthesizing potentially bioactive ni-
trogenous compounds and in the construction of new
sulfur–nitrogen and carbon–nitrogen bonds, we focused on
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101463.
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Intermolecular Imination and Amidation without Catalyst
expanding the scope of nitrogen sources and optimizing the
amidation reaction. Only a few suitable nitrogen sources
have been reported in the literature, such as trifluoroacet-
amide, 4-nitrobenzene-sulfonamide or p-tosylamide[4,9] N-
tosyliminophenyl-iodinane (PhI=NTs),[5] Bromamine-T[15]
or Chloroamine-T, 2-amino-isoindoline-1,3-dione, and az-
ide[16] compounds. Investigations on their chemistry, par-
ticularly with regard to reactions with alkenes, sulfoxides,
and sulfides, which could provide valuable insight into the
reactivity of amidation reactions, are thus important. To
gain further insight into the mode of C–H bond amidation
and the formation of sulfur–nitrogen bonds, it was consid-
ered of interest to examine the effect of N–H bond dissoci-
ation energies of nitrogen sources. The dissociation energies
of the N–H bond, to the best of our knowledge, have not
hitherto been probed in the context of amidation reactions.
Thus, in this paper, we report the effect of bond dissociation
energies of N–H bonds on amidation reactions. In addition,
the effect of the oxidant on the nitrogen source and sub-
strate was also studied. Furthermore, the intermolecular
amidation of sulfides, olefins, and saturated C–H bonds
with a series of nitrene sources was also examined and their
relative reactivity was compared (Scheme 2). These studies
have led to an improvement in the efficiency of amidation
reactions and to the discovery of nitrene-transfer reaction
rules for the insertion of N–R units into a variety of sub-
Results and Discussion
Effects of N–H Bond Dissociation Energies of Nitrene
Source
We investigated the effect of N–H dissociation energies
on the reactivity of the amidation reaction. Styrene was em-
ployed as a model substrate for the amidation in dichloro-
methane with PhI(OAc)2 as oxidant at room temperature
without any catalyst. Amines n3 and n4 (Table 1, entries 3
and 4) were the most effective for the amidation, but the
reaction hardly proceeded using amines n1 or n2 (Table 1,
entries 1 and 2) as nitrogen source under the same reaction
condition, unless under catalysis.[17] The aziridination of
styrene in dichloromethane using amines n5 or n6 (Table 1,
entries 5 and 6) as nitrogen sources only resulted in the
formation of oxidized mixtures of amines. When amine n7
was treated with PhI(OAc)2 under identical conditions, the
reaction rate was fast and only Hoffman rearrangement
product (aniline) was obtained in the reaction system. It is
thus clear that the N–H dissociation energies effect on the
reaction may be primarily linked with the stability of the
nitrogen source in the reaction system. Next, the reaction
may be linked with magnitude of N–H dissociation energies
(Figure 1).
Table 1. Calculated bond dissociation energies at different levels of
strates. We have exploited the insertion reaction to develop theory [kcal/mol].
a novel metal-catalyst-free imination of sulfides and azirid-
ination of olefins. This metal-free approach continues a ten-
dency toward green chemistry for the formation of C–N
and S–N bonds.
[a] At UB3LYP/6-31+G(d,p) level of theory. [b] At UB3P86-6-
311++G(2df,2p)//UB3L YP/6-31+G(d,p) level of theory.
All the calculations were performed using Gaussian 03
program.[18] Geometry optimization was carried out with-
out any constraint at the UB3LYP/6-31+G(d,p)[19,20] level
of theory (Method 1). Each optimized structure was con-
firmed by harmonic frequency analysis at the same calcula-
tional level as a true minimum with no imaginary fre-
Scheme 2. Nitrene source and substrates employed for the amid-
ation and imination by nitrene insertion.
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L. He, Y. Xue et al.
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were recovered after reaction times of several hours. How-
ever, interestingly, only sulfides and olefins were found to
react regioselectively in the imination of sulfides and azirid-
ination of olefins under similar conditions.
Aziridination of Olefins
To evaluate the efficiency of the oxidant and solvent, the
aziridination reaction of styrene with 4-amino-4H-1,2,4-tri-
azole using PhI (OAc)2 as oxidant was studied by using
different molecular ratios, base, and solvents; the results are
shown in Table 2. Our studies showed that the best yields
were obtained when 4 equiv. PhI(OAc)2 was employed as
the oxidant with a substrate/base/PhI(OAc)2/4-amino-4H-
1,2,4-triazole ratio of 1:6.0:4.0:4.0, in the presence of pow-
dered molecular sieves (4 Å) in CH2Cl2 at 0 °C for 20 h;
under these conditions, the aziridine derivatives were ob-
tained with moderate to high yield.
Figure 1. Influence of the bond dissociation energies on yield. The
reactivity of the amidation reaction increases with decreasing bond
dissociation energies. The amidation of styrene carried out in the
absence of a catalyst at 0–30 °C for 20 h using CH2Cl2 as solvent,
PhI(OAc)2 as oxidant, and n1–n7 as nitrogen source.
quency. The frequency calculations without scaling also
provided thermodynamic quantities such as the zero-point
vibrational energy, thermal correction, enthalpies, Gibbs
free energies, and entropies at a temperature of 298.15 K
and pressure of 101325 Pa. The single-point calculations at
the UB3P86-6-311++G(2df,2p) level[20] were performed on
the basis of the geometrical structures optimized at the
B3LYP/6-31+G(d,p) level (Method 2). Note that the en-
thalpies of each species obtained were calculated using the
electronic energies obtained using Methods 1 and 2 added
to the enthalpy correction obtained in the B3LYP/6-
31+G(d,p) method, respectively. The bond dissociation en-
ergies (BDEs) of N–H were calculated as the enthalpy
change of the following reaction at 298.15 K and
101.325 kPa.[21]
Table 2. Optimization of reaction conditions.
Entry
Base
Ratio (I:II:III:IV)[a]
Solvent
% Yield[b]
1
2
3
4
5
6
7
8
–
1:2.0:2.0:2.0
1:2.0:2.0:2.0
1:2.0:2.0:2.0
1:2.0:2.0:2.0
1:4.5:3.0:3.0
1:6.0:4.0:4.0
1:7.5:5.0:5.0
1:6.0:4.0:4.0
1:6.0:4.0:4.0
1:6.0:4.0:4.0
1:6.0:4.0:4.0
1:6.0:4.0:4.0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
ClCH2CH2Cl
THF
47
53
64
51
75
79
74
32
61
Al2O3
K2CO3
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
(g)
RNH2 Ǟ :NR(g) + 2H·(g)
(1)
9
That is:
10
11
12
trace
trace
trace
DMF
DMSO
(g)
BDE = H(:NR(g)) + 2H(H·(g)) – H(RNH2
Effect of Oxidant
)
(2)
[a] Reagents and conditions: I (alkene)/II (base)/III [PhI(OAc)2]/IV
(4-amino-4H-1,2,4-triazole), solvent (10 mL), 0 °C, 20 h. [b] Iso-
lated yield.
Besides PhI(OAc)2, oxidants PhI(OCOCF3)2, PhI=O,
MnO2, HgO, m-chloroperoxybenzoic acid (m-CPBA), N-
bromosuccinimide (NBS) or N-chlorosuccinimide (NCS)
were also employed in the amidation or imination reaction.
PhI(OAc)2 and PhI(OCOCF3)2 were the most effective for
the imination of sulfides and aziridination of olefins under
similar conditions.
When using styrene as a substrate, with a substrate/base/
PhI(OAc)2/4-amino-4H-1,2,4-triazole molecular ratio of
1:2.0:2.0:2.0, the product 4-(2-phenylaziridin-1-yl)-4H-
1,2,4-triazole was obtained with 53% yield (Table 2, en-
try 2). The reactivity of aziridination increased with increas-
ing amounts of 4-amino-4H-1,2,4-triazole and PhI(OAc)2.
The yield was dramatically raised to 79% (Table 2, entry 6)
by using 4-amino-4H-1,2,4-triazole as nitrogen source and
PhI(OAc)2 as oxidant, with alkene/tBuOK/PhI(OAc)2/4-
Effect of Substrate
The effect of substrates was investigated using several dif- amino-4H-1,2,4-triazole in
a
molecular ratio of
ferent substrates under strictly identical conditions. When 1:6.0:4.0:4.0. Upon examining the effect of bases, it was
substrates such as sulfides, olefins, allylic saturated hydro- found that tBuOK was more effective than other bases at
carbons, ethers, and arenes were treated with the PhI(OAc)2/ lower temperature. When the effect of temperature on the
RNH2/CH2Cl2 system under a nitrogen atmosphere, the ac- aziridination reaction was also tested, it was found that the
tivity of allylic saturated hydrocarbons, ethers, and arenes amidation reaction was best performed at 0 °C; when the
for amidation reactions was low and only starting materials temperature was increased to 30 °C, the yield of 4-(2-phen-
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Intermolecular Imination and Amidation without Catalyst
ylaziridin-1-yl)-4H-1,2,4-triazole decreased to trace Imination of Sulfoxides and Sulfides with 4-Amino-4H-
amounts. In addition, the use of molecule sieves (4 Å) was 1,2,4-triazole
found to be helpful for the aziridination reactions. Finally,
Sulfoxide and sulfide derivatives can also undergo an in-
it was established that dichloromethane was more effective
sertion reaction with 4-amino-4H-1,2,4-triazole as nitrogen
than other solvents under identical reaction conditions.
source to give the corresponding 4-(2-phenylaziridin-1-yl)-
To test the universality of the reaction system, several
4H-1,2,4-triazole derivatives, which can play a key role in
different olefins were examined. Most substrates gave the
the synthesis of bioactive compounds. Thus, we examined
corresponding product with moderate to high yields
the insertion reaction of 4-amino-4H-1,2,4-triazole with a
(Table 3, entries 1, 4, 5, and 9–11). However, use of styrene
series of sulfoxides and sulfides in CH2Cl2. At the beginning
derivatives with electron-withdrawing substituents in the or-
of this work, to evaluate the efficiency of the oxidant and
tho-position resulted in low yields (Table 3, for example, en-
solvent, the imination reaction of diphenyl sulfoxide with
tries 2 and 3) under identical conditions. Cyclohexene did
4-amino-4H-1,2,4-triazole was studied by using a range of
not give the product with high yield in the reaction system
oxidants and solvents; the results were shown in Table 4. It
(Table 3, entry6).
was found that only PhI(OAc)2 and PhI(OCOCF3)2 could
be used as oxidant for the imination of sulfoxides; other
oxidants, such as PhI=O, MnO2 and HgO, were much less
effective.
Table 3. Aziridination of olefins.[a]
Table 4. Optimization of oxidant and solvent.[a]
Entry
Solvent
Oxidant
% Yield[b] (conv.)
1
2
3
4
5
6
7
8
9
DMF
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OCOCF3)2
PhI=O
85 (33)
91 (39)
88 (35)
trace
trace
90 (39)
trace
–
CH2Cl2
CH3CN
THF
dioxane
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MnO2
HgO
–
[a] Reagents and conditions: substrate/4-amino-4H-1,2,4-triazole/
oxidant ratio 1:3.0:3.0, 0 °C to room temp., 2 h. [b] Isolated yield.
With the same procedure, several molecular ratios of sub-
strate/4-amino-4H-1,2,4-triazole/PhI(OAc)2, and reaction
times were tested in CH2Cl2 in the presence of Al2O3 and
4 Å molecule sieves; the results are listed in Table 5. In-
creasing the molecular ratio of substrate/4-amino-4H-1,2,4-
triazole/PhI(OAc)2 lead to an increase in substrate conver-
sion and product yield (Table 5, entries 5–7). Furthermore,
the use of excess PhI(OAc)2 was found to be favorable to
the yield. When using sulfinyldibenzene (3c) as a substrate
with 3c/4-amino-4H-1,2,4-triazole/PhI(OAc)2 in a molecu-
lar ratio of 1:1.5:1.5, the product dibenzyl-N-(1,2,4-triazol-
4-yl)sulfoximine was obtained with 77% yield (Table 5, en-
try 2). The yield was increased to 89% (Table 5, entry5) by
adding 4-amino-4H-1,2,4-triazole/PhI (OAc)2 to 3–4 equiv.
Therefore, the results shown in Table 5 demonstrate that the
reactivity of imination increases with the amount of 4-
amino-4H-1,2,4-triazole/PhI(OAc)2. We also examined the
effect of temperature, and it was found that longer reaction
times were needed to achieve similar yields at lower tem-
peratures (Table 5, entry1). Increase in temperature (60 °C)
[a] Reagents and conditions: alkenes/4-amino-4H-1,2,4-triazole/
PhI(OAc)2/tBuOK ratio 1:4.0:4.0:6.0, CH2Cl2 (10 mL), 0 °C, 20 h.
[b] Isolated yield.
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L. He, Y. Xue et al.
FULL PAPER
led to a decrease in reaction yield (Table 5, entry4). The method could provide a convenient way to prepare sulfox-
inclusion of Al2O3 and molecular sieves (4 Å) were found imines and sulfilimines from either sulfoxides or sulfides
to be helpful for the imination reactions.
through the use of simple, commercially available reagents
by a metal-catalyst-free imination reaction.
Table 5. Optimization of imination reaction conditions with sulfox-
ides.
Table 7. Imination of sulfides derivatives.[a]
Entry
T
[°C]
Molar ratio of substrate/
N-source/PhI(OAc)2
Time
[h]
% Yield
(conv.)
Entry R3
R4
Product % Yield[b] (conv.)
1
2
3
4
5
6
7
0
1:1.5:1.5
1:1.5:1.5
1:1.5:1.5
1:1.5:1.5
1:3.0:3.0
1:4.0:4.0
1:5.0:5.0
10
2
2
2
2
75 (30)
77 (31)
67 (27)
48 (13)
91 (39)
87 (40)
89 (38)
r.t.
40
60
r.t.
r.t.
r.t.
1
2
3
4
5
6
7
8
9
phenothiazine (PHT)
6a
6b
6c
6d
6e
6f
85 (40)
85 (52)
98 (67)
77 (51)
95 (75)
93 (74)
91 (65)
88 (100)
40 (66)
Bu
Ph
Ph
Ph
Ph
Ph
Bu
Bn
allyl
p-C6H4-NO2
Bu
2
2
o-C6H4-NO2
6g
6h
6i
(p-COOCH3)Ph Me
Ph Py
To test the universality of the metal-catalyst-free reaction
system, we applied several sulfoxides and sulfides to the im-
ination reaction. Almost all the substrates gave the corre-
sponding products with good yields, however, the conver-
sions were moderate (Tables 6 and 7, entries 1, 2, and 4).
In addition, the conversion of sulfinyldibenzene (Table 6,
entry3) was increased from 39 to 63% in the presence of
tBuOK at 0 °C for 4 h. Nevertheless, other sulfoxides gave
more than 90% conversion and only trace amounts of cor-
responding products 4 under these reaction conditions. The
nucleophilic sulfides showed higher reactivity than sulfox-
ides, giving the corresponding sulfilimines in good yields
(Table 7, entries 3, 5, 6, 7, and 8) under the same reaction
conditions. From these results, we can conclude that this
[a] Reagents and conditions: sulfoximine/4-amino-4H-1,2,4-tri-
azole/PhI(OAc)2/Al2O3 ratio 1.0:3.0:3.0:4.0, CH2Cl2 (10 mL), room
temperature, 2 h. [b] Isolated yield.
C–H Functionalization Reaction
The intermolecular amidation of saturated C–H bonds
using 4-amino-4H-1,2,4-triazole as a nitrene source was
also examined. Thus, α-saturated C–H bonds of ethers and
allylic sp3 C–H bonds of hydrocarbons such as tetra-
hydrofuran, 3,4-dihydro-1H-isochromene, 1,2,3,4-hydro-
naphthalene, and toluene were used as substrates with a
substrate/4-amino-4H-1,2,4-triazole/PhI(OAc)2 molecular
ratio of 1:3.0:3.0 in CH2Cl2 at room temp. for 24 h under a
nitrogen atmosphere. Unfortunately, activities for the C–H
insertion reaction were low, and only starting materials
were recovered. With the same procedure, several oxidants,
such as HgO, MnO2, PhI(CF3CO)2, and PhI=O were
tested, however, the formation of amidation product was
still not observed.
Table 6. Imination of sulfoxides with 4-amino-4H-1,2,4-triazole.[a]
Entry
R1
R2
Product
% Yield[b] (conv.)
1
2
3
4
5
6
7
8
Me
Bu
Ph
Bn
Ph
Ph
Ph
hexyl
Me
Bu
Ph
Bn
Me
Bu
Bn
hexyl
4a
4b
4c
4d
4e
4f
4g
4h
4i
51
Conclusions
89 (52)
91 (63)[c]
97 (48)
86 (52)
71 (51)
84 (56)
84 (51)
96 (55)
81 (52)
91 (65)
We have demonstrated a convenient and efficient pro-
cedure for the formation of sulfur–nitrogen bonds (Table 6,
entries 3 and 11, Table 7, entries 3, and 5–8) and carbon–
nitrogen bonds (Table 3, entries 1, 4, 5, 9, and 11) by direct
reaction with 4-amino-4H-1,2,4-triazole using PhI(OAc)2 as
oxidant in the absence of a catalyst under mild conditions.
These methods utilize the infrequently used nitrene-transfer
reaction and subsequent insertion to introduce polyazoles
units into carbon–carbon double bonds and sulfides. The
nitrene insertion reactivity correlates with calculated de-
creases in N–H bond dissociation energies. Further investi-
gation into the pharmacological activity of these sulfox-
9
10
11
(–CH2CH2–)2
Ph
Ph
p-C6H4-NO2
CH2CH2CN
4j
4k
[a] Reagents and conditions: sulfoximine/4-amino-4H-1,2,4-tri-
azole/PhI(OAc)2/Al2O3 ratio 1.0:3.0:3.0:4.0, CH2Cl2 (10 mL), room
temperature, 2 h. [b] Isolated yield. [c] The reaction was performed
with sulfoximine/4-amino-4H-1,2,4-triazole/PhI(OAc)2/tBuOK ra-
tio 1.0:3.0:3.0:3.0, CH2Cl2, 0 °C, 4 h.
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Intermolecular Imination and Amidation without Catalyst
4-[2-(p-Tolyl)aziridin-1-yl]-4H-1,2,4-triazole (2e): Following GP1
using 1-methyl-4-vinylbenzene and 4-amino-4H-1,2,4-triazole gave
2e (80% yield) as a pale-yellow solid. 1H NMR (400 MHz, CDCl3):
δ = 8.33 (s, 2 H), 7.24–7.00 (m, 4 H), 3.50–3.45 (m, 1 H), 2.93 (dd,
J = 8.2, 2.4 Hz, 1 H), 2.77 (dd, J = 8.2, 2.4 Hz, 1 H), 2.38 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.1, 138.6, 131.8,
129.5, 126.3, 46.5, 41.1, 21.2 ppm. HRMS: calcd. for C11H13N4 [M
+ H]+ 201.1140; found 201.1134.
imines, sulfilimines, and aziridines compounds, and into the
synthesis and application of chiral alkyl-aryl-N-(1,2,4-tri-
azol-1-yl)sulfoximines are underway and will be reported in
due course.
Experimental Section
7-(4H-1,2,4-Triazol-4-yl)-7-azabicyclo[4.1.0]heptane (2f): Following
GP1 using cyclohexene and 4-amino-4H-1,2,4-triazole gave 2f
(38% yield) as a pale-brown solid. H NMR (400 MHz, CDCl3): δ
= 8.25 (s, 2 H), 2.80–2.74 (m, 2 H), 2.14–2.04 (m, 2 H), 2.0–1.89
(m, 2 H), 1.48–1.36 (m, 2 H), 1.34–1.24 (m, 2 H) ppm. 13C
NMR(100 MHz, CDCl3): δ = 139.3, 72.8, 44.5, 19.5 ppm. HRMS:
calcd. for C8H12N4Na [M + Na]+ 187.0960; found 187.0958.
General: All reactions were performed under a nitrogen atmo-
sphere. Unless specified, all reagents were purchased from commer-
cial sources. Molecular sieves (4 Å) were dried at 200 °C and cooled
under reduced pressure prior to use. Solvents were purified accord-
ing to standard procedures. Silica gel F254 plates were used for
thin-layer chromatography (TLC); the spots were examined under
UV light at 254 nm and then developed in an iodine vapor. Flash
chromatography was performed on silica gel. 1H NMR spectra
were recorded with Bruker AC-E 200 MHz and Varian Mercury
400 MHz spectrometers with tetramethylsilane (TMS) as internal
standard and with chemical shifts (ppm) recorded relative to TMS.
The HRMS (ESI) spectra were recorded with a Bruker Daltonics
Data analysis 3.2 mass spectrometer.
1
4-[2-(3-Bromophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2g): Following
GP1 using 1-bromo-3-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2g (38% yield) as a pale-brown solid. 1H NMR (400 MHz,
CDCl3): δ = 8.35 (s, 2 H), 7.54–7.44 (m, 2 H), 7.32–7.20 (m, 2 H),
3.56–3.48 (m, 1 H), 3.00 (dd, J = 8.0, 2.4 Hz, 1 H), 2.76 (dd, J =
8.0, 2.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.0,
137.3, 131.5, 130.2, 129.1, 125.0, 122.7, 45.4, 41.4 ppm. HRMS:
calcd. for C10H10BrN4 [M + H]+ 265.0089; found 265.0086.
Synthesis of Aziridine. General Procedure 1 (GP1): A mixture of
alkene
(1.0 mmol),
4-amino-4H-1,2,4-triazole
(4.0 mmol),
PhI(OAc)2 (4.0 mmol), tBuOK (6.0 mmol), molecular sieves (4 Å),
and CH2Cl2 (8 mL) was stirred under a nitrogen atmosphere at
0 °C for approximately 20 h in a flame-dried flask. After consump-
tion of the starting material (the reaction was monitored by TLC),
the mixture was concentrated under reduced pressure. The resulting
product was purified by flash column chromatography (CHCl3/
CH3OH, 50:1).
4-[2-(4-Bromophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2h): Following
GP1 using 1-bromo-4-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2h (48% yield) as a pale-brown solid. 1H NMR (400 MHz,
CDCl3): δ = 8.36 (s, 2 H), 7.41 (dd, J = 6.8, 1.6 Hz, 2 H), 7.19 (dd,
J = 6.8, 1.6 Hz, 2 H), 3.51–3.49 (m, 1 H), 2.99 (dd, J = 8.4, 2.4 Hz,
1 H), 2.74 (dd, J = 8.4, 2.4 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 139.2, 134.1, 131.9, 128.0, 122.5, 45.7, 41.4 ppm.
HRMS: calcd. for C10H10BrN4 [M
265.0081.
+
H]+ 265.0089; found
4-(2-Phenylaziridin-1-yl)-4H-1,2,4-triazole (2a): Following GP1
using styrene and 4-amino-4H-1,2,4-triazole gave 2a (79% yield) as
a pale-brown solid. 1H NMR (400 MHz, CDCl3): δ = 8.34 (s, 2 H),
7.45–7.28 (m, 5 H), 3.54–3.51 (m, 1 H), 2.97 (dd, J = 8.2, 2.4 Hz,
1 H), 2.78 (dd, J = 8.2, 2.4 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDC13): δ = 139.2, 135.1, 128.8, 128.6, 126.4, 46.4, 41.2 ppm.
HRMS: calcd. for C10H11N4 [M + H]+ 187.0984; found 187.0980.
4-[2-(4-Chlorophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2i): Following
GP1 using 1-chloro-4-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2i (63% yield) as a pale-brown solid. 1H NMR (400 MHz,
CDCl3): δ = 8.34 (s, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.23 (d, J =
8.2 Hz, 2 H), 3.54–3.50 (m, 1 H), 2.99 (dd, J = 8.2, 2.4 Hz, 1 H),
2.73 (dd, J = 8.2, 2.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 139.2, 134.4, 133.7, 128.9, 127.7, 45.7, 41.4 ppm. HRMS: calcd.
for C10H9ClN4 [M + H]+ 221.0594; found 221.0590.
4-[2-(2-Chlorophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2b): Following
GP1 using 1-chloro-2-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2b (45% yield) as a pale-brown solid. 1H NMR (400 MHz,
CDCl3): δ = 8.43 (s, 2 H), 7.50–7.40 (m, 1 H), 7.38–7.22 (m, 3 H),
3.95–3.82 (m, 1 H), 3.01 (dd, J = 8.0, 2.0 Hz, 1 H), 2.81 (dd, J =
8.0, 2.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDC13): δ = 139.1,
134.4, 132.5, 129.8, 129.5, 127.3, 127.2, 44.3, 40.0 ppm. HRMS:
calcd. for C10H9ClN4 [M + H]+ 221.0594; found 221.0595.
4-[2-(3,4-Dimethoxyphenyl)aziridin-1-yl]-4H-1,2,4-triazole (2j): Fol-
lowing GP1 using 1,2-dimethoxy-4-vinylbenzene and 4-amino-4H-
1
1,2,4-triazole gave 2j (56% yield) as a pale-brown solid. H NMR
(400 MHz, CDCl3): δ = 8.35 (s, 2 H), 6.98–6.90 (m, 2 H), 6.80–
6.76 (m, 1 H), 3.96–3.86 (m, 6 H), 3.52–3.47 (m, 1 H), 2.94 (dd, J
= 8.0, 2.4 Hz, 1 H), 2.78 (dd, J = 5.6, 2.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 152.2, 145.1, 142.7, 137.5, 122.9, 111.3,
103.9, 56.0, 55.7, 47.0, 40.5 ppm. HRMS: calcd. for C12H15N4O2
[M + H]+ 247.1195; found 247.1183.
4-[2-(2-Fluorophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2c): Following
GP1 using 1-fluoro-2-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2c (32% yield) as a pale-brown solid. 1H NMR (400 MHz,
CDCl3): δ = 8.42 (s, 2 H), 7.41–7.33 (m, 1 H), 7.21–7.11 (m, 3 H),
3.81–3.74 (m, 1 H), 3.01 (dd, J = 8.4, 2.4 Hz, 1 H), 2.76 (dd, J =
5.6, 2.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 139.3,
130.4, 127.2, 124.5, 123.2, 115.6, 115.4, 41.3, 39.6 ppm. HRMS:
calcd. for C10H10FN4 [M + H]+ 205.0889; found 205.0895.
4-[2-(4-Methoxyphenyl)aziridin-1-yl]-4H-1,2,4-triazole (2k): Follow-
ing GP1 using 1-methoxy-4-vinylbenzene and 4-amino-4H-1,2,4-
triazole gave 2k (85% yield) as a pale-brown solid. 1H NMR
(400 MHz, [D6]DMSO): δ = 8.83 (s, 2 H), 7.30 (d, J = 8.4 Hz, 2
H), 6.94 (d, J = 8.4 Hz, 2 H), 3.76 (m, 4 H), 3.16 (dd, J = 8.4,
2.4 Hz, 1 H), 2.85 (dd, J = 8.0, 2.4 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.9, 139.1, 127.6, 126.7, 114.2, 55.3, 46.3,
40.9 ppm. HRMS: calcd. for C12H15N4O2 [M + H]+ 247.1195;
found 247.1183.
4-[2-(4-Fluorophenyl)aziridin-1-yl]-4H-1,2,4-triazole (2d): Following
GP1 using 1-fluoro-4-vinylbenzene and 4-amino-4H-1,2,4-triazole
gave 2d (75% yield) as a pale-yellow solid. 1H NMR (400 MHz,
CDCl3): δ = 8.34 (s, 2 H), 7.32–7.22 (m, 2 H), 7.16–7.04 (m, 2 H),
3.56–3.48 (m, 1 H), 2.96 (dd, J = 8.0, 2.4 Hz, 1 H), 2.75 (dd, J =
8.0, 2.0 Hz, 1 H) ppm. 13C NMR(100 MHz, CDCl3): δ = 159.0,
134.4, 126.0, 123.2, 123.1, 110.8, 110.6, 40.7, 36.3 ppm. HRMS:
calcd. for C10H10FN4 [M + H]+ 205.0889; found 205.0883.
Synthesis of Sulfoximines and Sulfilimines. General Procedure 2
(GP2): A mixture of sulfide or sulfoxide (1.0 mmol), 4-amino-4H-
1,2,4-triazole (3.0 mmol), PhI(OAc)2 (3.0 mmol), Al2O3 (4.0 mmol)
Eur. J. Org. Chem. 2012, 1554–1562
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1559

L. He, Y. Xue et al.
FULL PAPER
and molecular sieves (4 Å, 0.2 g), in a dried flask, CH2Cl2 (8 mL)
was stirred under a nitrogen atmosphere at 0 °C in a flame-dried
flask. The reaction was stirred at 0 °C to room temperature for 2–
4 h. After consumption of the starting material (reaction monitored
by TLC) the reaction mixture was concentrated under reduced
pressure. The resulting product was purified by flash column
chromatography (CHCl3/CH3OH, 25:1) to give the product.
Dihexyl-N-(1,2,4-triazol-4-yl)sulfoximine (4h): Following GP2 using
dihexyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4h (58 mg,
84% yield, 51% conversion) as a gray solid. H NMR (400 MHz,
CDCl3): δ = 8.17 (s, 2 H), 3.20–3.02 (m, 4 H), 1.89–1.76 (m, 4 H),
1.47–1.40 (m, 4 H), 1.33–1.25 (m, 8 H), 0.91–0.88 (t, J = 6.4 Hz, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.3, 49.3, 31.0, 28.0,
22.7, 22.2, 13.8 ppm. HRMS (ESI): calcd. for C14H29N4OS [M +
H]+ 301.2062; found 301.2057.
1
Dimethyl-N-(1,2,4-triazol-4-yl)sulfoximine (4a): Following GP2
using dimethyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4a
(43 mg, 51% yield) as a gray powder. 1H NMR (400 MHz, [D6]-
Tetramethylene-N-(1,2,4-triazol-4-yl)sulfoximine (4i): Following
GP2 using tetramethylenesulfoxide and 4-amino-4H-1,2,4-triazole
DMSO): δ = 8.42 (s, 2 H), 3.32 (s, 6 H) ppm. 13C NMR (100 MHz, gave 4i (101 mg, 96% yield, 55% conversion) as a white solid. H
1
[D6]DMSO): δ = 143.7, 38.4 ppm. HRMS (ESI): calcd. for
NMR (400 MHz, CDCl3): δ = 8.23 (s, 1 H), 8.19 (s, 1 H), 3.41 (m,
2 H), 3.11 (m, 2 H), 2.35 (m, 4 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 146.8, 143.1, 49.9, 23.8 ppm. HRMS (ESI): calcd. for
C6H11N4OS [M + H]+ 187.0654; found 187.0648.
C4H9N4OS [M + H]+ 161.0497; found 161.0492.
Dibutyl-N-(1,2,4-triazol-4-yl)sulfoximine (4b): Following GP2 using
dibutyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4b (47 mg,
89% yield, 52% conversion) as a gray powder. 1H NMR (400 MHz,
CDCl3): δ = 8.21 (s, 2 H), 3.23–3.06 (m, 4 H), 1.88–1.78 (m, 4
H), 1.54–1.45 (m, 4 H), 0.99 (t, J = 7.2 Hz, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 143.3, 49.1, 24.7, 21.7, 13.4 ppm. HRMS
(4-Nitrophenyl)phenyl-N-(1,2,4-triazol-4-yl)sulfoximine (4j): Follow-
ing GP2 using 4-nitrophenyl phenyl sulfoxide and 4-amino-4H-
1,2,4-triazole gave 4j (39 mg, 81% yield, 52% conversion) as a gray
1
solid. H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 8.4 Hz, 2 H),
(ESI): calcd. for C10H21N4OS [M + H]+ 245.1436; found 245.1432. 8.23 (d, J = 8.4 Hz, 2 H), 8.16 (s, 2 H), 8.06 (d, J = 8.0 Hz, 2 H),
7.79–7.72 (m, 1 H), 7.66–7.62 (t, J = 7.8 Hz, 2 H) ppm. 13C NMR
Diphenyl-N-(1,2,4-triazol-4-yl)sulfoximine (4c): Following GP2
(100 MHz, [D6]DMSO): δ = 143.4, 140.9, 135.8, 133.7, 130.9,
using diphenyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4c
130.8, 129.5, 125.6, 125.5 ppm. HRMS (ESI): Calcd. for
(83 mg, 91% yield, 63% conversion) as a gray powder. 1H NMR
C6H11N4OS [M + H]+ 330.0661; found 330.0658.
(400 MHz, CDCl3): δ = 8.16 (s, 2 H), 8.05–8.03 (m, 4 H), 7.69–7.65
(m, 2 H), 7.57–7.61 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ 3-[N-(4H-1,2,4-Triazol-4-yl)phenylsulfonimidoyl]propanenitrile (4k):
= 143.1, 135.5, 134.6, 130.0, 128.7 ppm. HRMS (ESI): calcd. for
Following GP2 using 3-(phenylsulfinyl)propanitrile sulfoxide and
4-amino-4H-1,2,4-triazole gave 4k (62 mg, 91% yield, 65%conver-
sion) as a pale-yellow solid. 1H NMR (400 MHz, CDCl3): δ = 8.11
(s, 2 H), 7.96 (m, 2 H), 7.79 (m, 1 H), 7.69 (m, 2 H), 3.92–3.84
(m, 1 H), 3.70–3.62 (m, 1 H), 3.11–2.94 (m, 2 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 143.4, 135.5, 132.1, 130.4, 130.1,
117.6, 46.7, 11.4 ppm. HRMS (ESI): calcd. for C11H12N5OS [M +
H]+ 262.0763; found 262.0738.
C14H13N4OS [M + H]+ 285.0810; found 285.0805.
Dibenzyl-N-(1,2,4-triazol-4-yl)sulfoximine (4d): Following GP2
using dibenzyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4d
(71 mg, 97% yield, 48% conversion) as a pale-brown solid. 1H
NMR (400 MHz, CDCl3): δ = 8.17 (s, 2 H), 7.52–7.43 (m, 6 H),
7.33–7.27 (m, 4 H), 4.38 (s, 4 H) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 148.5, 136.7, 134.1, 133.9, 132.3, 61.0 ppm. HRMS
(ESI): calcd. for C16H17N4OS [M + H]+ 313.1123; found 313.1119. N-Butyl-N-(1,2,4-triazol-4-yl)-10H-phenothiazine (6a): Following
GP2 using phenothiazine and 4-amino-4H-1,2,4-triazole gave 6a
Methylphenyl-N-(1,2,4-triazol-4-yl)sulfoximine (4e): Following GP2
using methyl phenyl sulfoxide and 4-amino-4H-1,2,4-triazole gave
(45 mg, 85% yield, 40% conversion) as a purple solid. 1H NMR
(400 MHz, [D6]DMSO): δ = 8.02 (d, J = 7.6 Hz, 2 H), 7.74 (t, J =
4e (53 mg, 86% yield, 52% conversion) as a gray powder. 1H NMR
7.6 Hz, 2 H), 7.40 (d, J = 8.0 Hz, 2 H), 7.33 (t, J = 8.4 Hz, 2 H),
(400 MHz, CDCl3): δ = 8.04 (s, 2 H), 7.92 (d, J = 8.0 Hz, 2 H),
6.83 (s, 2 H), 3.55 (m, J = 8.0 Hz, 2 H), 1.56–1.52 (m, 2 H), 1.47–
7.71 (t, J = 7.6 Hz, 1 H), 7.63 (t, J = 7.6 Hz, 2 H) ppm. 13C NMR
1.41 (m, 2 H), 0.97–0.94 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 142.9, 135.1, 134.6, 130.3, 128.8, 40.9 ppm.
(100 MHz, CDCl3): δ = 142.5, 141.5, 133.9, 131.9, 122.9, 115.1,
HRMS (ESI): calcd. for: C9H11N4OS [M + H]+ 223.0654; found
113.2, 48.3, 28.9, 19.8, 13.7 ppm. HRMS (ESI): calcd. for
223.0648.
C18H20N5S [M + H]+ 338.1439; found 338.1436.
Butylphenyl-N-(1,2,4-triazol-4-yl)sulfoximine (4f): Following GP2
Dibutyl-N-(1,2,4-triazol-4-yl)sulfilimine (6b): Following GP2 using
using butyl phenyl sulfoxide and 4-amino-4H-1,2,4-triazole gave 4f
dibutyl sulfides and 4-amino-4H-1,2,4-triazole gave 6b (77 mg,
(41 mg, 71% yield, 51% conversion) as a gray solid. 1H NMR
(400 MHz, CDCl3): δ = 8.06 (s, 1 H), 7.88 (d, J = 7.6 Hz, 2 H),
85% yield, 52% conversion) as a brown powder. 1H NMR
(400 MHz, CDCl3): δ = 8.05 (s, 2 H), 2.82–2.75 (m, 2 H), 2.58–
7.71 (t, J = 7.2 Hz, 1 H), 7.62 (t, J = 7.6 Hz, 2 H), 3.53–3.45 (m,
2.51 (m, 2 H), 1.91–1.77 (m, 4 H), 1.61–1.44 (m, 4 H), 1.01 (t, J =
1 H), 3.37–3.29 (m, 1 H), 1.93–1.84 (m, 1 H), 1.72–1.65 (m, 1 H),
7.2 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.8, 45.3,
1.50–1.40 (m, 1 H), 0.93 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
25.6, 21.8, 13.6 ppm. HRMS (ESI): calcd. for C10H21N4S
(100 MHz, CDCl3): δ = 143.1, 134.8, 133.7, 130.2, 129.2, 52.6, 23.8,
[M + H]+ 229.1487; found 229.1480.
21.4, 13.4 ppm. HRMS (ESI): calcd. for C14H22N2O2SNa [M +
Na]+ 305.1294; found 305.1284.
Benzylphenyl-N-(1,2,4-triazol-4-yl)sulfilimine (6c): Following GP2
using phenyl benzyl sulfides and 4-amino-4H-1,2,4-triazole gave 6c
(71.1 mg, 98% yield, 67% conversion) as a pale-yellow powder. 1H
NMR (400 MHz, CDCl3): δ = 8.14 (s, 2 H), 7.70 (s, 1 H), 7.63–
7.53 (m, 4 H), 7.39–7.38 (m, 3 H), 7.31–7.28 (m, 2 H), 4.36 (q, J
= 7.2 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 144.3,
135.3, 132.8, 130.5, 130.1, 129.3, 128.8, 127.3, 55.2 ppm. HRMS
(ESI): calcd. for C15H15N4S [M + H]+ 283.1017; found 283.1021.
Benzylphenyl-N-(1,2,4-triazol-4-yl)sulfoximine (4g): Following GP2
using phenyl benzyl sulfoxide and 4-amino-4H-1,2,4-triazole gave
1
4g (60 mg, 84% yield, 56% conversion) as a pale-brown solid. H
NMR (400 MHz, CDCl3): δ = 8.12 (s, 2 H), 7.66 (d, J = 8.0 Hz, 3
H), 7.52 (t, J = 8.0 Hz, 2 H), 7.38 (t, J = 7.6 Hz, 1 H), 7.29 (t, J =
7.6 Hz, 2 H),7.10 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 143.1, 134.9, 132.4, 131.4, 129.9, 129.9, 129.8, 128.9,
125.4, 59.7 ppm. HRMS (ESI): calcd. for C15H15N4OS [M + H]+
299.0966; found 299.0961.
Allylbenzyl-N-(1,2,4-triazol-4-yl)sulfilimine (6d): Following GP2
using allyl benzyl sulfides and 4-amino-4H-1,2,4-triazole gave 6d
1560
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1554–1562

Intermolecular Imination and Amidation without Catalyst
(53 mg, 77% yield, 51% conversion) as a gray solid. 1H NMR
(400 MHz, [D6]DMSO): δ = 8.72 (s, 2 H), 7.49–7.47 (m, 5 H), 5.89–
5.78 (m, 1 H), 5.22–5.14 (m, 2 H), 4.1 (d, J = 6.4 Hz, 2 H) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 141.8, 134.3, 132.3, 130.0,
129.8, 129.5, 126.1, 64.6 ppm. HRMS (ESI): calcd. for C11H13N4S
[M + H]+ 233.0861; found 233.0863.
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2 H), 7.90 (s, 2 H), 7.85 (d, J = 8.8 Hz, 2 H), 7.71 (m, 1 H), 7.62
(t, J = 7.6 Hz, 2 H), 7.52 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 143.8, 142.8, 134.8, 130.8, 130.0. 129.7,
128.9, 126.6, 124.0 ppm. HRMS (ESI): calcd. for C14H12 N5O2S
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Butylphenyl-N-(1,2,4-triazol-4-yl)sulfilimine (6f): Following GP2
using butyl phenyl sulfide and 4-amino-4H-1,2,4-triazole gave 6f
1
(109 mg, 93% yield, 74% conversion) as a yellow-brown solid. H
NMR (400 MHz, CDCl3): δ = 7.83 (s, 2 H), 7.63–7.61 (m, 1 H),
7.58–7.51 (m, 4 H), 3.27–3.20 (m, 1 H), 3.02–2.95 (m, 1 H), 1.88–
1.73 (m, 2 H), 1.61–1.45 (m, 2 H), 0.99 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 144.2, 133.0, 130.3, 129.2, 127.6,
45.5, 25.7, 21.7, 13.5 ppm. HRMS (ESI): calcd. for C12H16N4S [M
+ H]+ 249.1174; found 249.1175.
[5]
N-(1,2,4-Triazol)phenyl-(2-nitrophenyl)sulfilimine (6g): Following
GP2 using phenyl (2-nitrophenyl) sulfide and 4-amino-4H-1,2,4-
triazole gave 6g (109 mg, 91% yield, 65% conversion) as a pale-
yellow solid. 1H NMR (400 MHz, [D6]DMSO): δ = 8.78 (d, J =
7.6 Hz, 1 H), 8.48 (s, 1 H), 8.43 (d, J = 8.0 Hz, 1 H), 8.27 (m, 1
H), 7.99 (t, J = 7.8 Hz, 1 H), 7.67 (d, J = 7.2 Hz, 2 H), 7.63–7.56
(m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 143.7, 142.9,
134.7, 133.7, 130.7, 130.0, 129.7, 129.1, 128.9, 126.6, 124.0 ppm.
HRMS (ESI): calcd. for C14H12N5O2S [M + H]+ 314.0712; found
314.0721.
Methyl 4-[Methyl-N-(4H-1,2,4-triazol-4-yl)sulfinimidoyl]benzoate
(6h): Following GP2 procedure using methyl 4-(methylthio)benzo-
ate and 4-amino-4H-1,2,4-triazole gave 6h (63 mg, 88% yield) as a
1
white solid. H NMR (400 MHz, CDCl3): δ = 8.22 (m, 2 H), 7.82
(s, 2 H), 7.66 (d, J = 8.0 Hz, 2 H), 3.98 (s, 3 H), 2.94 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 165.2, 143.9, 140.4, 134.1, 131.2,
127.2, 52.7, 29.9 ppm. HRMS (ESI): calcd. for C11H13N4OS [M +
H]+ 265.0759; found 265.0755.
[6]
[7]
Phenylpyrimidinyl-N-(1,2,4-triazol-4-yl)sulfilimine (6i): Following
GP2 using pyrimidinyl phenyl sulfoxide and 4-amino-4H-1,2,4-tri-
azole gave 6i (97 mg, 40% yield, 66% conversion) as a pale yellow
solid. 1H NMR (400 MHz, CDCl3): δ = 9.03 (s, 1 H), 8.59 (s, 2 H),
7.46–7.41 (m, 2 H), 7.40–7.35 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 142.8, 141.9, 135.4, 134.0, 130.4, 130.0, 129.1,
125.0 ppm. HRMS (ESI): calcd. for C12H10N6S [M
271.0766; found 271.0770.
+
H]+
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the NMR spectra, the Cartesian coordinates [Å] and
calculated energies and the thermal corrections to the enthalpy of
the structures optimized at the UB3LYP/6-31+G(d,p) level of
theory.
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Acknowledgments
This work was financially supported by the National Natural Sci-
ence Foundation of China (NSFC) (grant number 21072131).
Eur. J. Org. Chem. 2012, 1554–1562
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Received: October 7, 2011
Published Online: January 26, 2012
1562
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1554–1562