Preparation, Characterization, and Reactivity of Aliphatic Amino Iodane(III) Reagents

Article abstract of DOI:10.1002/ejoc.202001373

The preparation of a new class of aliphatic amino iodane(III) reagents has been realized with the N-TMS?amine and acetoxybenziodazole participated in the formation of N?I bond. The amino-containing iodane(III) reagent 2 d was characterized by single-crystal X-ray diffraction, which revealed the expected hypervalent iodane distorted T-shaped geometry. A practical copper-catalyzed, directed electrophilic amination of aryl amines employing amino-iodane(III) as amination agents was disclosed that proceeded smoothly without external additives.

Full text of DOI:10.1002/ejoc.202001373

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Preparation, characterization and reactivity of aliphatic amino
iodane(III) reagents
Authors: Yue Zhang, Jing Lu, Tianlei Lan, Shaoling Cheng, Wei Liu,
and Chao Chen
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of the final Version of Record (VoR). This work is currently citable by
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published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001373
Link to VoR: https://doi.org/10.1002/ejoc.202001373
01/2020

10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
Preparation, characterization and reactivity of aliphatic amino
iodane(Ⅲ) reagents
Yue Zhang,[a][b] Jing Lu,[a][b] Tianlei Lan,[a][b] Shaoling Cheng,[a] Wei Liu*[a] and Chao Chen*[b][c]
Abstract: The preparation of a new class of aliphatic amino
iodane(III) reagents has been realized with the N-TMS-amine and
acetoxybenziodazole participated in the formation of N-I bond. The
amino-containing iodane(III) reagent 2d was characterized by single-
crystal X-ray diffraction, which revealed the expected hypervalent
iodane distorted T-shaped geometry. A practical copper-catalyzed,
directed electrophilic amination of aryl amines employing amino-
iodane(III) as amination agents was disclosed that proceeded
smoothly without external additives.
Introduction
In 2002, Zhdankin’s group reported the preparation of the
complexes of benziodoxole with aromatic amines, which are
useful as mild electrophiles and selective oxidizing reagents[6]. In
Many saturated nitrogen-containing heterocycles feature
prominently in pharmaceuticals, such as treatments for
depression (paroxetine), diabetes (gliclazide), leukaemia
(alvocidib), malaria (mefloquine) (Scheme 1).[1] The development
of rapid and efficient methods for the introduction of amino motifs
into an organic molecule has the potential to promise candidates
for the synthesis of various biologically active and medicinally
important compounds[2]. Therefore, the development of amino
group-transfer reagents is a desirable synthesis goal.
2015, Kiyokawa and co-workers disclosed
a protocol for
preparing the hypervalent iodane reagents including
a
phthalimidate group, which could be applicable for use in the
oxidative amination[7]. In 2017, Bolm’s group demonstrated a
range of sulfoximidoyl-containing hypervalent iodane reagents
and developed a photocatalytic addition of this hypervalent
iodane reagents to styrenes[8]. Recently, our group investigated a
series of bench-stable carbazole-containing hypervalent iodane
reagents to introduce a carbazole group to aromatic heterocycle
compounds[9]. (Scheme 2A)
OH
O
O
HN
H
F
N
HO
NH
O
O
O
HO
HO
Cyclic hypervalent iodanes, as electrophilic amination reagents,
O
NH
O
Cl
S
O
have attracted significant interest for organic synthesis recently[10]
It is known that C-N bonds are usually formed by the nucleophilic
attack of a nitrogen to an electrophilic carbon previously bonded
to a leaving group in a typical SN2 type of reaction[11]. The reverse
process in which the reagent for this “electrophilic amination” can
provide an electron deficient nitrogen group, ” N+ ” is interesting
because of the synthetic possibilities it opens. Furthermore,
electrophilic nitrogen sources are an increasingly popular class of
reagents for the formation of C–N bonds[12]. Although the
aforementioned nitrogen-containing hypervalent iodane reagents
have been well-explored, the N-atom is commonly required to be
protected, such as phenyl, acyl, p-toluenesulfonyl and Phthaloyl.
To the best of our knowledge, the preparation, structure and
reactivity of the aliphatic aminobenziodoxole has never been
documented to date. Herein, we reported on the preparation and
X-ray structural characterization of aliphatic amino iodane (III)
reagents. These new reagents are stable compound soluble in
dichloromethane and dimethyl sulfoxide and can be used for the
Cu-catalyzed directed electrophilic amination of aryl amines
(Scheme 2B).
.
N
CF3
CF3
N
N
H
Mefloquine
(malaria)
Alvocidib
(leukaemia)
Paroxetine
(anti-depressant)
Gliclazide
(diabetes)
Scheme 1. Alicyclic amines containing drug molecules.
Cyclic hypervalent iodane reagents, especially benziodoxoles,
have been an extraordinary increase in the use of group-transfer
reagents in organic synthesis.[3] Essentially, nitrogen-containing
iodane(III) reagents, possessing specific steric and electronic
properties, are of particular importance in medicinal chemistry[3a,4]
In recent years, extensive studies of the benziodoxole-based
hypervalent iodane reagents containing I-N bonds achieved great
success to construct C-N bonds with step and atom economy[5].
.
[a]
[b]
[c]
Y. Zhang, J. Lu, T-L. Lan, Prof. Dr. S –L. Cheng, Prof. Dr. W. Liu
College of Science & Material Science & Chemical Engineering
Institute, Tianjin University of Science and Technology, Tianjin 300457,
P. R. China.
E-mail: liuwei2006@tust.edu.cn
Y. Zhang, J. Lu, T-L. Lan, Prof. Dr. C. Chen
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical
Biology (Ministry of Education, MOE), Department of Chemistry.
Tsinghua University, Beijing 100084, China
E-mail: chenchao01@mails.tsinghua.edu.cn
Prof. Dr. C. Chen
State Key Laboratory of Elemento-Organic Chemistry
Nankai University, Tianjin 300071, China
Supporting information for this article is given via a link at the end of the
document.((Please delete this text if not appropriate))
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10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
A) Previous work
Of note, the reaction was amenable to scale-up without loss of
its yield when the reaction was performed in 92% yield in 10 mmol
scale. This method was also identified for the preparation of
aliphatic amino iodane(III) reagent 2g by using N-TMS-Et2N as
the amine source, although the yield was not satisfactory.
Gratifyingly, all iodane(III) reagents could be stored for one year
or more if held at a temperature of 0-5 ℃.
R1
R
R
O
S
OTf
R2
PhthN
I
O
N
I
O
I
O
N
N
I
O
O
O
O
O
Zhdankin's work
Kiyokawa's work
Bolm's work
Chen's work
B) This work
NHCOPy
R
TMS
R1
N
R2
Complexes 2a-2g were characterized by 1H and 13C NMR
spectroscopy. The structure of 2d was unambiguously
established by a single-crystal X-ray analysis (Figure 1). In
particular, structural data revealed a distorted T-shaped geometry
expected for hypervalent iodane with an endocyclic C-I-O bond
angle of 74.6 (5) ° and N-I-O bond angle of 164.7(5) °. The length
of bonds to the iodine atom, I-N 2.093(11) Å, I-O 2.369(13) Å, I-C
2.132(14) Å, are all within the range of typical single covalent
R1 NHCOPy
N
AcO
I
O
I
O
R1 R2
N
R2
O
O
R
Scheme 2. Recently developed amino-containing hypervalent iodane
reagents.
Results and Discussion
bonds in organic derivatives of polyvalent iodane[13]
.
In the attempt to prepare a new type of amino-containing
hypervalent iodane reagents, we managed initially with
morpholine bearing NH group as substrates to react with
acetoxybenziodoxolone for the preparation of 1-morpholino-1, 2-
benzo[d]iodaoxol-3-(1H)-one 2a. Unfortunately, our attempt along
this line was unsuccessful. Encouraged by our group work on
carbazole-substituted hypervalent iodane reagents,[9] N-TMS-
Morpholine was applied as the amine source next. However, with
10 mol% KF as an additive, acetoxybenziodoxolone and 1a were
carried out in dry CH3CN and stirred for 24 h at room temperature,
and compound 2a remained inaccessible, as well as the color of
the reaction solution turned grey. We speculated that excessive
reaction time caused decomposition of the product. Following this,
it was found that the change of color of the reaction from yellowish
to orange was observed and the color was held on for a while. It
might be mentioned that this color did not change any more
indicating the end of the reaction. The total time needed for the
complete reaction was about 3 hours. Product 2a was isolated in
the form of a yellowish solid by filtration from the reaction mixture
and washing with acetonitrile and ether. Meanwhile, it was
characterized by 1H and 13C spectroscopy. To our delight, the
desired hypervalent iodane product 2a was obtained in 94% yield.
Moreover, hypervalent iodane reagents containing five-, six-,
seven-membered cyclic amines all proceed smoothly to afford the
desired products in good yields (Scheme 3).
N
I
O
O
Figure 1. Single-crystal X-ray diffraction structure of 2d. The thermal ellipsoids
are shown at the 35% probability level. (CCDC 1970681)
Table 1.The scope of substrate 3. a, b
O
NHCOPy
R
O
N
I
O
NHCOPy
Cu(OAc)2•H2O (100 mol%)
N
O
+
1,4-Dioxane
R
80 °C, 12 h, N2
4
2
3
O
NHCOPy
O
NHCOPy
OMe
O
NHCOPy
O
NHCOPy
N
N
N
N
F
R
R=H 89%
4ap 51%
4aq 30%
4ao 58%
4aa
4ab
4ac
4ad
4ae
4af
R=Me 90%
R=i-pr 94%
R=t-Bu 86%
R=OMe 81%
R=Ph 87%
R=F 56%
O
NHCOPy
O
NHCOPy
O
NHCOPy
N
N
N
Br
R1
N
R2
4ag
4at 44%
4as 23%
4ar 39%
TMS
AcO
I
O
I
O
4ah
R=Cl 63%
KF (10 mol%)
N
+
R1 R2
4ai
4aj
4ak
R=Br 54%
R=I 79%
O
O
CH3CN
rt, 3 h
O
NHCOPy
O
NHCOPy
OMe
O
NHCOPy
R=OCF3 48%
N
N
N
1
2
4al
R=COOMe 45%
4am
4an
R=CN 34%
Cl
Cl
MeO
O
N
I
O
S
N
I
O
Boc
N
N
I
O
N
I
O
R=NO2 trace
4au
92%
4av 87%
4aw 94%
O
O
O
O
a Reaction condition: 3 (0.2 mmol), 2 (0.5 mmol), Cu(OAc)2ꞏH2O(100 mol%), in
1,4-Dioxane (4 mL) at 80 ℃ for 12 h. b isolated yield.
2d: 89%
2c
2b: 85%
: 74%
O
2a
: 94%
92%a
After successful synthesis of these nitrogen-containing
iodane(III) reagents 2, the direct amination reactions on C-H
bonds were explored. We chose the easily available aniline 3a
and amino-containing iodine(III) 2a as model substrates to
explore the optimized reaction conditions.[17] Having established
the optimal reaction conditions (see SI), the scope of substrate
was investigated to test the generality and limitations of this
electrophilic amination. As shown in Table 1, aniline moieties
N
N
I
O
N
I
O
I
O
O
O
2e: 68%
2g: 26%
2f: 69%
Scheme 3. Scope of amino-containing hypervalent iodane reagents. Reaction
conditions: 1 (3.0 mmol), acetoxybenziodoxolone (3.0 mmol), KF (10 mol%), in
CH3CN (5 mL) at room temperature. a10 mmol scale.
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10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
containing electron-rich and electron-deficient substrates were
first employed to react with substrate 2a. Notably, diverse
functional groups in different positions were well-tolerated under
the standard reaction conditions. As expected, electron-rich
substrates furnished better yields than electron-deficient anilines.
Electron-donating methyl, isopropyl, t-butyl, methoxy, phenyl
groups at the para position (3b-3f) provided good yields and
moderately electron-deficient halogen (F, Cl, Br, I) substituents at
the same position gave moderate yields (3g-3j). Strongly
electron-withdrawing group, such as trifluoromethoxy, ester,
cyano, nitro, afforded generally lower yields (3k-3n) as a result of
lower conversion. Methyl, methoxy, fluoro, bromo substitution at
the meta position afforded lower yields (3o-3r) than their
corresponding para substituted counterparts. The amination is
proved to be sensitive toward steric encumbrance near the
targeted C-H bond: the less hindered ortho position was
preferentially aminated in the case of substrates bearing a meta
substituent, while the 1-naphthyl derivative was aminated at C2
(3t). The presence of a substituent at the ortho position reduced
reactivity (3s), presumably because of increased steric
encumbrance. Meta-dimethoxy, meta-dichloro and meta-
dimethyl-substituted anilines gave excellent yields (3u-3w).
Gratifyingly, other six-membered cyclic aminobenziodoxoles,
such as thiomorpholine, piperidine and N-Boc-protected
piperazine also provided the o-position amination products in
moderate to high yields (2a-2d). Unfortunately, besides six-
membered cyclic aminobenziodoxoles, this method is not
applicable for five-, seven-membered cyclic aminobenziodoxoles
and diethylaminobenziodoxoles (2e-2g). Switching from 2-
picolinamide protected aniline 3a to 2-picolinamide protected
naphthylamine 3t, reacted with seven-membered cyclic
aminobenziodoxoles to afford trace amount of desired product.
Only hypervalent iodine reagents containing a six-membered
amino group could be used in the amination and this might be
attributed to their better stability than other hypervalent iodine
reagents.
In order to gain insight into the mechanism of Cu-catalyzed
directed electrophilic amination of aryl amines with amino-
containing iodane(III) reagent, a control experiment, radical
inhibition was conducted (Scheme 4). The reaction was
completely suppressed when 2.5 equiv of TEMPO (2,2,6,6-
tetramethyl-1-piperidinyloxy) was added, implying that a radical
reaction pathway might be involved in the transformation. This
observation is also consistent with a SET mechanism.
Following amination of six-membered cyclic amine morpholine-
benziodoxoles, we turned our attention to explore the reactivity of
other hypervalent iodane reagents and 2-picolinamide protected
aniline 3a was chosen as model substrate (Table 2).
O
NHCOPy
TEMPO (2.5 equiv)
+
O
N
I
O
NHCOPy
N
O
Cu(OAc)2•H2O (110 mol%)
1,4-Dioxane
4aa
0%
2a
3a
80 °C, 12 h, N2
Table 2. Scope of the hypervalent iodane reagents 2.a, b
Scheme 4. Control experiments
From this control experiment and previous literature reports [14]
,
R1
R1 NHCOPy
Cu(OAc)2•H2O (100 mol%)
NHCOPy
N
I
O
+
N
a plausible mechanistic cycle was proposed. Initial coordination
of copper with bidentate 2-picolinamide may generate complex Ⅰ.
Subsequently, one-electron reduction of complex Ⅰ lead to the
formation of copper(Ⅰ) complex Ⅱ. Followed by ligand exchange,
deprotonation, may provide the desired product and copper(Ⅱ) for
the subsequent runs (Scheme 5) .
R2
R2
1,4-Dioxane
O
R
R
80 °C, 12 h, N2
3
4
2
Substrate 2
Product 4 (yielda)
Substrate 2
Product 4 (yielda)
S
N
I
O
S
NHCOPy
O
NHCOPy
O
N
I
O
N
N
O
O
O
2b
4ba
61%
O
2a
4aa
N
H
89%
Boc
N
O
N
N
H
N
NHCOPy
NHCOPy
Boc
N
N
I
O
N
I
O
N
N
N
Cu(OAc)2
COOH
O
O
AcOH
I
4da
87%
4ca
2d
I
2c
46%
2AcOH
O
O
NHCOPy
0%
NHCOPy
N
I
O
N
O
N
N
N
O
N
Ⅱ
O
Cu
N
N
H
I
Ⅰ
Cu
N
O
OAc
2e
4ea
4fa
0%
2f
O
O
Ⅰ
SET
N
I
O
NHCOPy
NHCOPy
N
I
O
O
N
O
N
O
O
N
Ⅳ
4ga
Ⅰ
0%
2g
Cu
N
2f
4ft
trace
N
OAc
Ⅱ
Cu
N
O
O
I
a Reaction condition: 3 (0.2 mmol), 2 (0.5 mmol), Cu(OAc)2ꞏH2O(100 mol%), in
1,4-Dioxane (4 mL) at 80 ℃ for 12 h. b isolated yield.
Ⅱ
O
I
N
O
O
O
N
+
Ⅲ
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10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
Scheme 5. Proposed mechanism.
equiv) and Cu(OAc)2·H2O (0.1 mmol, 1.0 equiv). Then 1, 4-dioxane (1.0
mL) was added and the mixture was stirred at 80 ℃ for 12 h. After cooling
to room temperature, the mixture was extracted with EtOAc (5 mL×3) and
washed with saturated aq. NaHCO3 solution (5 mL×3), followed by brine
solution (5 mL×3) and dried over anhydrous Na2SO4 and concentrated
under reduce pressure. The resulting residue was purified by silica gel
flash chromatography (petroleum ether/EtOAc) to afford the desired ortho
aminated product.
Conclusions
In conclusion, the 1-amino-1, 2-benziodoxoles have been
prepared with acetoxybenziodazole and various N-TMS-amino
via a rapid and efficient N-I coupling reaction. These new
hypervalent iodane reagents show relative stability in both solid
state and solution, and the structure of which was established by
single-crystal X-ray diffraction. Of importance, employing readily
accessible 2-picolinamide in the presence of copper salt, amino-
containing iodane(Ⅲ) reagents, so-called aminobenziodazole,
served as electrophilic amination reagents, providing o-position
amination products in moderate to high yields. Thus, we anticipate
that the electrophilic amination reagents will be highly applicable
in scientific research.
1-morpholino-1, 2-benzo[d]iodaoxol-3-(1H)-one (2a). Yellowish solid,
yield: (0.94 g, 94%); mp: 132-134 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.21
(d, J = 8.2 Hz, 1H), 8.03 (dd, J = 7.4, 1.8 Hz, 1H), 7.94 – 7.85 (m, 1H), 7.66
(t, J = 7.2 Hz, 1H), 3.71 (t, J = 4.5 Hz, 4H), 3.51 (d, J = 4.5 Hz, 4H); 13
C
NMR (101 MHz, DMSO-d6) δ 167.58, 134.18, 133.50, 132.07, 130.74,
126.28, 117.72, 69.28, 56.35; ESI-HRMS: m/z calcd for C11H12INO3
[M+Na]+: 355.9753; found: 355.9754.
1-thiomorpholino-1, 2-benzo[d]iodaoxol-3-(1H)-one (2b). Yellowish
solid yield: (0.89 g, 85%); mp: 131-133 ℃; 1H NMR (400 MHz, DMSO-d6)
δ 7.81 (d, J = 7.9 Hz, 1H), 7.45 (dd, J = 7.5, 1.9 Hz, 1H), 7.35 (d, J = 7.7
Hz, 1H), 7.07 – 6.97 (m, 1H), 3.21 – 3.13 (m, 4H), 2.80 – 2.74 (m, 4H); 13
C
NMR (101 MHz, DMSO-d6) δ 167.56, 134.24, 133.37, 132.06, 130.72,
126.23, 118.00, 58.09, 30.00; ESI-HRMS: m/z calcd for C11H12INO2S
[M+Na]+: 371.9631; found: 371.9635.
Experimental Section
General Comments: All commercial reagents were used as received
unless otherwise noted. Solvents were dried using standard methods and
distilled before use. Column chromatography was performed on silica gel
(particle size 10-40μm). Unless otherwise stated, all reactions were carried
out in oven-dried glassware under an atmosphere of N2 and were
monitored by TLC. 1H and 13C spectra were recorded on a JEOL AL-400
MHz spectrometer frequency in CDCl3 and CD3SOCD3 solvent using TMS
as the internal standard. Chemical shift (δ) were given in ppm, referenced
to the residual proton resonance of CDCl3 (7.26) or DMSO-d6 (2.54), to the
carbon resonance of CDCl3 (77.16) or DMSO-d6 (40.45). Multiplicities are
recorded as: s=singlet, d=doublet, t=triplet, dd=doublet of doublets,
m=multiplet. Coupling constants, J were reported in Hertz unit (Hz). HRMS
(m/z) were measured using ESI mode.
Tert-butyl-4-(1,
2-benzo[d]iodaoxol-3-(1H)-yl)
piperazine-1-
carboxylate (2c). White solid, yield: (0.96 g, 74%); mp: 135-137 ℃; 1H
NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 8.2 Hz, 1H), 7.98 (td, J = 9.3,
8.3, 2.8 Hz, 1H), 7.85 (td, J = 7.8, 1.7 Hz, 1H), 7.62 (t, J = 7.3 Hz, 1H),
3.19 (s, 8H), 1.37 (s, 9H); 13C NMR (101 MHz, DMSO-d6) δ 167.54, 154.51,
134.22, 133.41, 132.06, 130.76, 126.33, 117.74, 79.63, 55.72, 28.57; ESI-
HRMS: m/z calcd for C16H21IN2O4 [M+Na]+: 455.0433; found: 455.0438.
1-(piperidin-1-yl)-1, 2-benzo[d]iodaoxol-3-(1H)-one (2d). White solid,
yield: (0.88 g, 89%); mp: 107-111 ℃; 1H NMR (400 MHz, Chloroform-d) δ
8.28 (d, J = 7.5 Hz, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.75 (t, J = 7.8 Hz, 1H),
7.58 (t, J = 7.3 Hz, 1H), 3.56 (s, 4H), 1.88 – 1.39 (m, 6H); 13C NMR (101
MHz, Chloroform-d) δ 167.91, 133.64, 132.82, 132.64, 130.57, 125.03,
117.00, 58.05, 29.30, 23.31; ESI-HRMS: m/z calcd for C12H14INO2
[M+Na]+: 354.0067; found: 354.0065.
General procedure for the preparation of N-TMS-amino 1a-1f. A 100
mL sealed tube containing a stir bar was added anhydrous DCM (20 mL),
then alicyclic amines (10 mmol 1.0 equiv) was added under nitrogen
atmospere. Solution was cooled down to 0℃ in an ice bath and Et3N (20
mmol, 2.8 mL, 2.0 equiv) was added and stirred at 0 ℃ for 0.5 h, then
trimethylchlorosilane (12 mmol, 1.51 mL, 1.2 equiv ) was added dropwise
into the cooled solution. The reaction micture was stirred at room
temperature for overnight. After completion, the solvent and excess
trimethylchlorosilaneand was remove under reduced pressure. Then,
hexane (20 mL) was added to the residue and the mixture was stirred for
0.5 h. Then the mixture was filtered and washed with hexane (10 mL×2).
The filtrate was concentrated by rotary evaporation to give the desired
product (1a-1f).
X-Ray crystal structure analysis of 2d (CCDC number: 1970681).
Single Crystal suitable for XRD was obtained from a solution in DCM/PE.
Formula: C12H14INO2, M = 331.14, Colorless crystal, 0.40 x 0.02 x 0.02
mm, a = 25.721(4), b = 25.721(4), c = 9.6397(16), α = 90.00°, β = 90.00°,
γ = 120.00° , V = 5523(2) Å3 , ρcalc = 1.792 gcm-3 , μ = 20.392 mm-1 , Z =
18, triclinic, space group P-1,
λ = 1.54184 Å, T = 173 K. Data
completeness=0.953, Theta(max)=75.178, R(reflections)=0.0918(1329),
wR2(reflections)= 0.2923( 2423).
1-(pyrrolidin-1-yl)-1, 2-benzo[d]iodaoxol-3-(1H)-one (2e). Yellowish
solid, yield: (0.66 g, 68%); mp: 92-96 ℃; 1H NMR (400 MHz, DMSO-d6) δ
7.98 (d, J = 7.3 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.85 – 7.75 (m, 1H), 7.60
(t, J = 7.3 Hz, 1H), 3.47 (s, 4H), 1.84 – 1.68 (m, 4H); 13C NMR (101 MHz,
DMSO-d6) δ 167.46, 134.00, 133.76, 131.91, 130.68, 126.00, 117.88,
56.54, 26.41; ESI-HRMS: m/z calcd for C11H12INO2 [M+Na]+: 339.9913;
found: 339.9919.
General procedure for the preparation of amino-hypervalent iodane
reagents. To a sealed tube was charge with 1-acetoxy-1,2-benziodoxol-
3-(1H)-one (3.0 mmol, 0.92 g) and KF (0.3 mmol, 17.4 mg). Then the tube
was evacuated and recharged with N2 for three times and dry CH3CN (5
mL) and N-TMS-amino 1 (3.0 mmol) was added. The reaction mixture was
stirred at room temperature for 3 h. It should be mentioned that the
excessive reaction time causes decomposition of the product. After
completion, the desired products was isolated in the form of a yellowish or
white solid by filtration from the reaction mixture and washing with
acetonitrile (5 mL×2) and ether (5 mL×2). The solid compounds were
stored at 4 ℃.
1-(azepan-1-yl)-1, 2-benzo[d]iodaoxol-3-(1H)-one (2f). Yellowish solid,
yield: (0.71 g, 69%); mp: 87-90 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.03
– 7.91 (m, 2H), 7.84 (t, J = 7.7 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 3.65 (d, J
= 38.4 Hz, 4H), 1.61 (s, 8H); 13C NMR (101 MHz, DMSO-d6) δ 167.44,
134.05, 133.74, 132.09, 130.72, 125.90, 118.77, 60.14, 32.09, 27.01; ESI-
HRMS: m/z calcd for C13H16INO2 [M+Na]+: 368.0225; found: 368.0228.
General procedure for the ortho amination of picolinamide. In a 25mL
sealed tube containing a star bar was added corresponding picolinamide
(0.1 mmol, 1.0 equiv), amino-hypervalent iodine reagent (0.25 mmol, 2.5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
1-(diethylamino)-1, 2-benzo[d]iodaoxol-3-(1H)-one (2g). Orange soild,
yield: (0.25 g, 26%); mp: 82-84 ℃; 1H NMR (400 MHz, DMSO-d6) δ 7.74
(d, J = 7.6 Hz, 1H), 7.40 – 7.32 (m, 1H), 7.29 (d, J = 7.4 Hz, 1H), 6.93 (s,
1H), 2.85 (q, J = 7.3 Hz, 4H), 1.19 (t, J = 7.2 Hz, 6H); 13C NMR (101 MHz,
DMSO-d6) δ 172.12, 148.21, 139.29, 128.94, 128.54, 127.95, 93.84,
41.74, 11.94; ESI-HRMS: m/z calcd for C11H14INO2 [M+Na]+: 342.0096;
found: 342.0097.
N-(4-chloro-2-morpholinophenyl)picolinamide (4ah)[16]. Yellow solid,
yield: 63%; 1H NMR (400 MHz, Chloroform-d) δ 11.00 (s, 1H), 8.64 (d, J =
4.6 Hz, 1H), 8.52 (d, J = 8.7 Hz, 1H), 8.27 (d, J = 7.8 H z, 1H), 7.90 (t, J =
7.7 Hz, 1H), 7.48 (dd, J = 7.6, 4.8 Hz, 1H), 7.15 (dd, J = 8.8, 2.5 Hz, 1H),
7.10 (d, J = 2.4 Hz, 1H), 4.16 – 3.83 (m, 4H), 3.04 – 2.84 (m, 4H); 13C NMR
(101 MHz, Chloroform-d) δ 161.92, 150.24, 148.34, 143.03, 137.77,
131.62, 128.97, 126.59, 125.23, 122.51, 120.74, 120.62, 67.51, 52.36.
N-(2-morpholinophenyl)picolinamide (4aa)[14c],[15],[16],[17]. White solid,
yield: 89%; 1H NMR (400 MHz, Chloroform-d) δ 11.14 (s, 1H), 8.65 (d, J =
4.6 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H), 7.90 (td, J =
7.7, 1.7 Hz, 1H), 7.47 (dd, J = 7.7, 4.7 Hz, 1H), 7.27 – 7.13 (m, 2H), 7.11
(d, J = 7.1 Hz, 1H), 4.02 – 3.94 (m, 4H), 2.99 – 2.92 (m, 4H); 13C NMR
(101 MHz, Chloroform-d) δ 161.97, 150.59, 148.31, 141.95, 137.68,
133.10, 126.41, 125.40, 124.17, 122.47, 120.17, 119.68, 67.71, 52.53.
N-(4-bromo-2-morpholinophenyl)picolinamide (4ai) [14c], [17].White solid,
yield: 54%; 1H NMR (400 MHz, Chloroform-d) δ 11.01 (s, 1H), 8.64 (dd, J
= 4.8, 1.6 Hz, 1H), 8.48 (d, J = 8.7 Hz, 1H), 8.28 (d, J = 7.7 Hz, 1H), 7.90
(td, J = 7.7, 1.8 Hz, 1H), 7.48 (dd, J = 7.4, 4.9 Hz, 1H), 7.31 (dd, J = 8.8,
2.3 Hz, 1H), 7.26 – 7.24 (m, 1H), 4.12 – 3.83 (m, 4H), 3.05 – 2.83 (m, 4H);
13C NMR (101 MHz, Chloroform-d) δ 161.95, 150.25, 148.34, 143.23,
137.77, 132.14, 128.24, 126.60, 123.67, 122.52, 120.99, 116.55, 67.52,
52.40.
N-(4-methyl-2-morpholinophenyl)picolinamide (4ab)[17]. White solid,
yield: 90%; 1H NMR (400 MHz, Chloroform-d) δ 11.03 (s, 1H), 8.64 (d, J =
4.6 Hz, 1H), 8.44 (d, J = 8.2 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 7.89 (t, J =
7.5 Hz, 1H), 7.46 (dd, J = 7.4, 4.8 Hz, 1H), 7.05 – 6.90 (m, 2H), 3.97 (t, J
= 4.5 Hz, 4H), 2.94 (t, J = 4.4 Hz, 4H), 2.33 (s, 3H); 13C NMR (101 MHz,
Chloroform-d) δ 161.74, 150.69, 148.28, 141.88, 137.64, 133.86, 130.43,
126.30, 125.76, 122.40, 120.80, 119.55, 67.72, 52.55, 21.30.
N-(4-iodo-2-morpholinophenyl)picolinamide
(4aj)[14c],[16]
.
White
crystalline, yield: 79%; 1H NMR (400 MHz, Chloroform-d) δ 11.03 (s, 1H),
8.65 (d, J = 4.7 Hz, 1H), 8.35 (d, J = 8.7 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H),
7.91 (t, J = 7.7 Hz, 1H), 7.49 (t, J = 8.1 Hz, 2H), 7.42 (d, J = 1.7 Hz, 1H),
3.97 (t, J = 4.5 Hz, 4H), 2.93 (t, J = 4.5 Hz, 4H); 13C NMR (101 MHz,
Chloroform-d) δ 161.97, 150.25, 148.33, 143.30, 137.77, 134.35, 132.92,
129.55, 126.60, 122.52, 121.33, 87.14, 67.52, 52.41.
N-(4-isopropyl-2-Morpholinophenyl)picolinamide (4ac)[17]. White solid,
yield: 94%; 1H NMR (400 MHz, Chloroform-d) δ 11.03 (s, 1H), 8.64 (d, J =
4.8 Hz, 1H), 8.47 (d, J = 8.2 Hz, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.94 – 7.81
(m, 1H), 7.53 – 7.40 (m, 1H), 7.06 (dd, J = 8.4, 2.0 Hz, 1H), 7.01 (d, J =
1.8 Hz, 1H), 4.06 – 3.61 (m, 4H), 2.96 (t, J = 4.5 Hz, 4H), 2.91 – 2.81 (m,
1H), 1.24 (d, J = 6.9 Hz, 6H); 13C NMR (101 MHz, Chloroform-d) δ 161.73,
150.70, 148.28, 145.05, 141.93, 137.62, 130.70, 126.29, 122.99, 122.40,
119.63, 118.13, 67.73, 52.57, 34.06, 24.19.
N-(2-morpholino-4-(trifluoromethoxy)phenyl)picolinamide (4ak)[14c]
.
White solid, yield: 48%; 1H NMR (400 MHz, Chloroform-d) δ 11.00 (s, 1H),
8.65 (d, J = 4.8 Hz, 1H), 8.59 (d, J = 9.0 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H),
7.91 (td, J = 7.8, 1.6 Hz, 1H), 7.49 (dd, J = 7.5, 4.9 Hz, 1H), 7.05 (dd, J =
8.6, 2.6 Hz, 1H), 6.99 (d, J = 2.5 Hz, 1H), 4.12 – 3.86 (m, 4H), 3.07 – 2.77
(m, 4H); 13C NMR (101 MHz, Chloroform-d) δ 161.99, 150.18, 148.35,
145.23, 143.10, 137.78, 131.71, 126.64, 122.55, 120.36, 117.64, 113.57,
67.47, 52.30.
N-(4-(tert-butyl)-2-Morpholinophenyl)picolinamide (4ad)[17]
.
White
solid, yield: 86%; 1H NMR (400 MHz, Chloroform-d) δ 11.04 (s, 1H), 8.64
(d, J = 4.3 Hz, 1H), 8.50 – 8.43 (m, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.88 (d,
J = 1.8 Hz, 1H), 7.50 – 7.38 (m, 1H), 7.23 – 7.15 (m, 2H), 3.97 (t, J = 4.4
Hz, 5H), 3.06 – 2.77 (m, 4H), 1.31 (s, 9H); 13C NMR (101 MHz, Chloroform-
d) δ 161.76, 150.70, 148.29, 147.31, 141.60, 137.62, 130.45, 126.29,
122.40, 122.14, 119.25, 117.00, 67.76, 52.58, 34.79, 31.53.
methy 3-morpholino-4-(picolinamido)benzoate(4al)[14c],[16],[17]
. White
solid, yield: 45%; 1H NMR (400 MHz, Chloroform-d) δ 11.30 (s, 1H), 8.86
– 8.50 (m, 2H), 8.29 (d, J = 8.1 Hz, 1H), 7.90 (t, J = 6.7 Hz, 2H), 7.84 (s,
1H), 7.50 (s, 1H), 3.99 (dt, J = 6.2, 3.0 Hz, 4H), 3.89 (d, J = 2.3 Hz, 3H),
2.97 (dd, J = 6.0, 2.9 Hz, 4H); 13C NMR (101 MHz, Chloroform-d) δ 166.81,
162.31, 150.12, 148.39, 141.62, 137.80, 137.32, 127.42, 126.75, 125.47,
122.64, 121.72, 118.81, 67.60, 52.47, 52.16.
N-(4-methoxy-2-morpholinophenyl)picolinamide
(4ae)[14c],[15],[17]
.
White crystalline solid, yield: 81%; 1H NMR (400 MHz, Chloroform-d) δ
10.86 (s, 1H), 8.73 – 8.59 (m, 1H), 8.56 – 8.41 (m, 1H), 8.27 (d, J = 7.6 Hz,
1H), 7.88 (d, J = 1.8 Hz, 1H), 7.45 (t, J = 3.8 Hz, 1H), 6.72 (q, J = 3.3 Hz,
2H), 3.96 (dd, J = 5.5, 3.4 Hz, 4H), 3.80 (d, J = 3.3 Hz, 3H), 2.93 (dt, J =
4.5, 3.1 Hz, 4H); 13C NMR (101 MHz, Chloroform-d) δ 156.41, 150.68,
148.26, 143.45, 137.64, 126.41, 126.25, 122.32, 120.65, 108.72, 107.34,
67.61, 55.61, 52.42.
N-(4-cyano-2-morpholinophenyl)picolinamide (4am)[14c][17].White solid,
yield: 34%; 1H NMR (400 MHz, Chloroform-d) δ 11.26 (s, 1H), 8.71 (d, J =
8.6 Hz, 1H), 8.66 (d, J = 4.9 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H), 7.93 (td, J =
7.7, 1.7 Hz, 1H), 7.57 – 7.46 (m, 2H), 7.40 (d, J = 1.8 Hz, 1H), 4.00 (dd, J
= 5.2, 3.4 Hz, 4H), 2.96 (dd, J = 5.1, 3.4 Hz, 4H); 13C NMR (101 MHz,
Chloroform-d) δ 162.41, 149.72, 148.44, 142.11, 137.94, 137.33, 129.90,
127.01, 124.02, 122.74, 119.69, 119.10, 106.92, 67.42, 52.27.
N-(3-morpholino-[1, 1´-buphenyl]-4-yl)picolinamide (4af)[14c] [17]
,
. White
N-(2-morpholino-4-nitrophenyl)picolinamide (4an). Yellow solid, yield:
trace; 1H NMR (400 MHz, Chloroform-d) δ 11.34 (s, 1H), 8.77 (dd, J = 9.1,
2.9 Hz, 1H), 8.67 (d, J = 4.0 Hz, 1H), 8.30 (d, J = 8.2 Hz, 1H), 8.11 (dd, J
= 9.0, 2.6 Hz, 1H), 8.07 – 8.01 (m, 1H), 7.97 – 7.92 (m, 1H), 7.58 – 7.49
(m, 1H), 4.01 (dd, J = 5.6, 3.2 Hz, 4H), 3.03 – 2.98 (m, 4H); 13C NMR (101
MHz, Chloroform-d) δ 161.56, 150.25, 148.36, 143.09, 137.76, 131.52,
128.96, 126.56, 125.21, 122.55, 120.73, 120.62, 67.53, 52.34. ESI-HRMS:
m/z calcd for C16H16N4O4 [M+H]+: 329.1174; found: 329.1146.
solid, yield: 87%; 1H NMR (400 MHz, Chloroform-d) δ 11.16 (s, 1H), 8.65
(d, J = 8.2 Hz, 2H), 8.31 (d, J = 7.8 Hz, 1H), 7.91 (s, 1H), 7.58 (d, J = 7.7
Hz, 2H), 7.51 – 7.46 (m, 1H), 7.43 (t, J = 7.4 Hz, 3H), 7.38 (s, 1H), 7.32 (s,
1H); 13C NMR (101 MHz, Chloroform-d) δ 161.95, 150.54, 148.34, 142.32,
140.87, 137.71, 137.20, 132.31, 128.90, 127.24, 126.97, 126.46, 124.02,
122.49, 119.93, 118.95, 67.72, 52.60.
N-(4-fluoro-2-morpholinophenyl)picolinamide (4ag)[14c],[16]. White solid,
yield: 56%; 1H NMR (400 MHz, Chloroform-d) δ 10.90 (s, 1H), 8.64 (d, J =
4.6 Hz, 1H), 8.53 (dd, J = 8.5, 6.2 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.90
(t, J = 7.6 Hz, 1H), 7.47 (dd, J = 7.6, 5.0 Hz, 1H), 6.87 (d, J = 9.6 Hz, 2H),
3.97 (t, J = 4.5 Hz, 4H), 2.93 (t, J = 4.5 Hz, 4H); 13C NMR (101 MHz,
Chloroform-d) δ 161.77, 160.57, 158.14, 150.37, 148.31, 143.52, 143.45,
137.74, 129.08, 126.49, 122.46, 120.84, 120.76, 111.51, 111.29, 107.82,
107.58, 67.48, 52.31.
N-(5-methyl-2-morpholinophenyl)picolinamide (4ao)[16]. Yellow solid,
yield: 58%; 1H NMR (400 MHz, Chloroform-d) δ 11.14 (s, 1H), 8.64 (d, J =
5.0 Hz, 1H), 8.43 (d, J = 1.9 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 7.90 (d, J =
7.7 Hz, 1H), 7.46 (dd, J = 7.5, 4.8 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 3.96
(m, 4H), 2.91 (m, 4H), 2.35 (s, 3H); 13C NMR (101 MHz, Chloroform-d) δ
161.93, 150.68, 148.31, 139.53, 137.66, 133.34, 132.90, 126.36, 124.67,
122.43, 120.21, 120.01, 67.75, 52.69, 21.47.
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10.1002/ejoc.202001373
European Journal of Organic Chemistry
FULL PAPER
N-(5-methoxy-2-morpholinophenyl)picolinamide (4ap)[16]. Brown solid,
yield: 51%; 1H NMR (400 MHz, Chloroform-d) δ 11.85 (s, 1H), 8.67 (td, J
= 7.4, 6.1, 3.0 Hz, 1H), 8.27 (dd, J = 11.6, 8.0 Hz, 2H), 8.03 (d, J = 7.9 Hz,
1H), 7.88 (td, J = 7.8, 2.0 Hz, 1H), 7.48 (dd, J = 7.5, 1H), 6.65 (d, J = 8.5
Hz, 1H), 4.00 – 3.93 (m, 4H), 3.84 (s, 4H), 3.74 – 3.57 (m, 3H); 13C NMR
(101 MHz, Chloroform-d) δ162.35, 158.45, 150.74, 148.39, 137.59, 133.63,
133.15, 128.13, 126.32, 122.49, 111.58, 107.17, 68.39, 55.34, 50.41.
3.91 (d, J = 1.9 Hz, 4H), 3.83 (s, 3H), 3.79 (s, 3H), 3.60 (ddd, J = 11.7, 9.7,
5.0 Hz, 2H), 2.59 (d, J = 11.8 Hz, 2H); 13C NMR (101 MHz, Chloroform-d)
δ 162.36, 159.03, 158.95, 150.74, 148.39, 137.57, 137.35, 126.32, 122.34,
121.61, 95.28, 95.20, 68.46, 55.64, 55.25, 50.72.
N-(2-thiomorpholinophenyl)picolinamide (4ba)[15]. Yellow solid, yield:
61%; 1H NMR (400 MHz, Chloroform-d) δ 11.07 (s, 1H), 8.68 (dt, J = 4.8,
1.3 Hz, 1H), 8.58 (dd, J = 8.1, 1.5 Hz, 1H), 8.29 (dd, J = 7.9, 1.1 Hz, 1H),
7.90 (td, J = 7.7, 1.7 Hz, 1H), 7.47 (ddd, J = 7.6, 4.7, 1.2 Hz, 1H), 7.22 –
7.12 (m, 2H), 7.12 – 7.05 (m, 1H), 3.24 – 3.10 (m, 4H), 2.95 (d, J = 6.3 Hz,
4H); 13C NMR (101 MHz, Chloroform-d) δ 162.01, 150.58, 148.36, 143.18,
137.66, 133.09, 126.41, 125.51, 124.10, 122.49, 120.91, 119.63, 54.65,
28.86.
N-(5-fluoro-2-morpholinophenyl)picolinamide (4aq)[16]
. White solid,
yield: 30%; 1H NMR (600 MHz, Chloroform-d) δ 11.27 (s, 1H), 8.70 – 8.64
(m, 1H), 8.39 (dd, J = 10.9, 3.0 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.96 –
7.88 (m, 1H), 7.24 – 7.16 (m, 1H), 7.12 (dd, J = 8.8, 5.2 Hz, 1H), 4.06 –
3.99 (m, 1H), 4.01 – 3.96 (m, 4H), 2.95 – 2.90 (m, 4H); 13C NMR (151 MHz,
Chloroform-d) δ162.23, 150.19, 148.41, 141.97, 137.80, 133.48, 128.11,
126.66, 122.61, 121.43, 121.37, 110.27, 67.72, 52.78.
tert-butyl
4-(2-(
picolinamido)phenyl)piperazine-1-carboxylate
(4ca)[14c],[15],[16]. White solid, yield: 46%; 1H NMR (400 MHz, Chloroform-d)
δ 11.09 (s, 1H), 8.65 (d, J = 4.6 Hz, 1H), 8.58 (d, J = 8.1 Hz, 1H), 8.29 (d,
J = 7.8 Hz, 1H), 7.95 – 7.85 (m, 1H), 7.47 (dd, J = 7.6, 4.8 Hz, 1H), 7.19
(d, J = 1.8 Hz, 1H), 7.16 – 7.05 (m, 2H), 3.70 (s, 4H), 2.89 (t, J = 4.9 Hz,
4H), 1.49 (s, 9H); 13C NMR (101 MHz, Chloroform-d) δ 161.98, 154.88,
150.56, 148.37, 141.99, 137.67, 133.02, 126.39, 125.43, 124.13, 122.48,
120.18, 119.72, 52.12, 28.55.
N-(5-bromo-2-morpholinophenyl)picolinamide (4ar)[14c],[15]. White solid,
yield: 39%; 1H NMR (400 MHz, Chloroform-d) δ 11.09 (s, 1H), 8.78 (d, J =
2.3 Hz, 1H), 8.64 (dd, J = 4.8, 1.5 Hz, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.90
(td, J = 7.8, 1.7 Hz, 1H), 7.48 (dd, J = 7.6, 4.7 Hz, 1H), 7.29 – 7.11 (m, 1H),
7.01 (d, J = 8.5 Hz, 1H), 4.14 – 3.78 (m, 4H), 2.91 (dd, J = 5.7, 3.4 Hz, 4H);
13C NMR (101 MHz, Chloroform-d) δ 162.02, 150.15, 148.36, 140.86,
137.78, 134.29, 126.94, 126.65, 122.57, 122.49, 121.64, 118.58, 67.57,
52.41.
N-(2-(piperdin-1-yl)phenyl)picolinamide (4da)[14c],[15],[16],[17]. White solid,
yield: 87%; 1H NMR (400 MHz, Chloroform-d) δ 11.13 (s, 1H), 8.65 (d, J =
4.6 Hz, 1H), 8.57 (d, J = 7.9 Hz, 1H), 8.29 (d, J = 7.8 Hz, 1H), 7.88 (t, J =
7.8 Hz, 1H), 7.45 (dd, J = 7.5, 5.0 Hz, 1H), 7.14 (dt, J = 9.6, 3.6 Hz, 2H),
7.08 (d, J = 7.3 Hz, 1H), 3.12 – 2.57 (m, 4H), 1.84 (p, J = 5.6 Hz, 4H), 1.62
(d, J = 6.4 Hz, 2H); 13C NMR (101 MHz, Chloroform-d) δ 148.26, 143.75,
137.51, 133.10, 126.19, 124.62, 123.96, 122.39, 120.15, 119.43, 53.81,
26.83, 24.43.
N-(2-methyl-6-morpholinophenyl)picolinamide (4as)[14c],[16],[17]. White
solid, yield: 23%; 1H NMR (400 MHz, Chloroform-d) δ 10.02 (s, 1H), 8.66
(d, J = 4.4 Hz, 1H), 8.27 (dd, J = 7.7, 3.3 Hz, 1H), 7.94 – 7.86 (m, 1H), 7.48
(dd, J = 7.7, 4.2 Hz, 1H), 7.21 – 7.12 (m, 1H), 7.03 (dd, J = 7.8, 2.9 Hz,
1H), 6.93 (dd, J = 7.9, 3.1 Hz, 1H), 3.74 (t, J = 4.5 Hz, 4H), 2.95 – 2.78 (m,
4H), 2.33 (d, J = 3.2 Hz, 3H); 13C NMR (101 MHz, Chloroform-d) δ 162.45,
148.32, 147.29, 137.61, 135.98, 126.83, 126.54, 126.49, 122.68, 116.65,
67.50, 52.29, 19.62.
The Supporting Information file contains the experimental steps and 1H,
13C, spectrum of compounds 2a-2g and 4aa-4aw, X-ray crystal spectra of
compounds 2d and optimized reaction conditions.
N-(2-morpholinonaphthalen-1-yl)picolinamide (4at)[14c],[15],[16],[17]. Light
brown crystalline solid, yield: 44%; 1H NMR (400 MHz, Chloroform-d) δ
10.28 (s, 1H), 8.71 (d, J = 4.8 Hz, 1H), 8.34 (d, J = 7.7 Hz, 1H), 7.93 (d, J
= 1.6 Hz, 1H), 7.88 (d, J = 8.6 Hz, 1H), 7.80 (d, J = 8.5 Hz, 2H), 7.55 –
7.49 (m, 1H), 7.47 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.37 (d, J
= 8.8 Hz, 1H), 3.83 – 3.76 (m, 4H), 2.99 (t, J = 4.5 Hz, 4H); 13C NMR (101
MHz, Chloroform-d) δ 163.49, 150.09, 148.38, 144.18, 137.72, 131.26,
129.72, 128.11, 128.05, 126.65, 126.31, 126.27, 125.02, 124.61, 122.87,
118.67, 67.57, 52.15.
CCDC 1970681 (for 2d) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
Acknowledgments
N-(3, 5-dichloro-2-morpholinophenyl)picolinamide (4au)[15]
. White
This work was supported by The National Key Research and
Development Program of China (2016YFB0401400), National
Natural Science Foundation of China (21871158 and 21672120),
the Fok Ying Tong Education Foundation of China (Grant No.
151014), and Foundation of Beijing Laviana Pharma Co., Ltd (No.
1800110001).
solid, yield: 92%; 1H NMR (400 MHz, Chloroform-d) δ 11.81 (s, 1H), 8.67
(dd, J = 8.1, 3.7 Hz, 2H), 8.27 (d, J = 7.8 Hz, 1H), 8.05 – 7.81 (m, 1H), 7.64
– 7.40 (m, 1H), 7.04 (d, J = 2.8 Hz, 1H), 4.08 – 3.91 (m, 4H), 3.81 (dd, J =
11.5, 3.4 Hz, 2H), 2.65 (d, J = 11.6 Hz, 2H); 13C NMR (101 MHz,
Chloroform-d) δ 162.40, 150.01, 148.41, 138.80, 137.80, 134.81, 133.26,
126.79, 124.82, 122.67, 117.69, 68.10, 49.39.
Keywords: cyclic hypervalent iodine • aliphatic amino • group-
N-(3, 5-dimethyl-2-morpholinophenyl)picolinamide (4av)[16]
. White
solid, yield: 87%; 1H NMR (400 MHz, Chloroform-d) δ 11.74 (s, 1H), 8.65
(dd, J = 4.7, 1.5 Hz, 1H), 8.35 (d, J = 2.0 Hz, 1H), 8.26 (d, J = 7.9 Hz, 1H),
7.93 – 7.81 (m, 1H), 7.44 (dd, J = 7.5, 4.7 Hz, 1H), 6.64 (d, J = 2.2 Hz, 1H),
4.04 (dd, J = 11.1, 2.4 Hz, 2H), 3.92 (dd, J = 10.9, 2.9 Hz, 2H), 3.59 – 3.43
(m, 2H), 2.71 (d, J = 11.8 Hz, 2H), 2.35 (s, 3H), 2.29 (s, 3H); 13C NMR (101
MHz, Chloroform-d) δ 162.02, 150.84, 148.24, 137.62, 136.77, 136.20,
136.04, 135.39, 127.40, 126.28, 122.41, 117.43, 68.27, 50.27, 21.46,
19.57.
transfer reagents • aniline derivatives • electrophilic amination
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Yue Zhang, Jing Lu, TianLei Lan,
Shaoling Cheng, Wei Liu*, Chao Chen*.
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Preparation, characterization, and
reactivity of aliphatic amino iodane(Ⅲ)
reagents
The preparation and X-ray structural characterization of aliphatic amino iodane (III) reagents
has been realized. These new reagents could be used for the Cu-catalyzed directed
electrophilic amination of aryl amines.
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