bond activation nickel-catalyzed n-vinylation of ... · vinod g. landge, jagannath rana, murugan...
TRANSCRIPT
1
Nickel-Catalyzed N-Vinylation of Heteroaromatic amines via C-H
bond Activation
Vinod G. Landge, Jagannath Rana, Murugan Subaramanian, and Ekambaram Balaraman*
Catalysis Division, Dr. Homi Bhabha Road, CSIR-National Chemical Laboratory (CSIR-NCL),
Pune - 411008, INDIA.
Contents
1. General Information S2
2. Experimental Section S2-S3
3. Synthetic Application S4
4. Mechanistic Investigation S5-S11
5. Characterization Data S12-S26
6. References S26
7. Spectra S28-S86
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2017
2
1. General Information
All catalytic experiments were carried out using standard Schlenk techniques. All
solvents were reagent grade or better. Deuterated solvents were used as received. p-cymene and
toluene were refluxed over sodium/benzophenone ketyl and distilled under argon atmosphere
and stored over sodium. Metal salts and other chemicals used in catalysis reactions were used
without additional purification. Thin layer chromatography (TLC) was performed using silica gel
precoated glass plates, which were visualized with visualized with UV light at 254 nm or under
iodine. Column chromatography was performed with SiO2 (Silicycle Siliaflash F60 (230-400
mesh). 1H NMR (400 or 500 MHz), 13C{1H} NMR (100 MHz) spectra were recorded on the
NMR spectrometer. Deuterated chloroform was used as the solvent, and chemical shift values (δ)
are reported in parts per million relative to the residual signals of this solvent [δ 7.26 for 1H
(chloroform-d), δ 77.2 for 13C{1H} (chloroform-d). Abbreviations used in the NMR follow-up
experiments: br, broad; s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. GC analysis was
carried out using a HP-5 column (30 m, 0.25 mm, 0.25μ). Mass spectra were obtained on a
GCMS-QP 5000 instruments with ionization voltages of 70 eV. High resolution mass spectra
(HRMS) were obtained on a High-resolution mass spectra (HRMS) were obtained by fast atom
bombardment (FAB) using a double focusing magnetic sector mass spectrometer and electron
impact (EI) ionization technique (magnetic sector-electric sector double focusing mass analyzer).
HPLC analysis was performed on Agilent Technologies 1260 Infinity with UV detector.
2. Experimental Section
2.1 Synthesis of Starting Materials
All the starting materials (N-(pyrimidine-2-yl)anilinesS1-S2 and β-bromostyrenesS3 were
prepared in accordance with the literature method.
2.2 Synthesis of [D1]-1c
Aniline 1c (300 mg, 1.88 mmol), [Cp*RhCl2]2 (5.0 mol %), Cu(OAc)2.H2O (1.88 mmol), D2O
(1.1 mL, 10.3 equiv) were placed in a 25 mL Schlenk tube and HFIP (1.5 mL) was added under
3
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
0.971.001.950.992.00
CHLOROFORM-d
6.77
6.78
6.79
6.98
6.99
7.00
7.12
7.15
7.17
7.27
7.38
8.46
8.47
8.5 8.0 7.5 7.0Chemical Shift (ppm)
0.971.001.950.992.00
CHLOROFORM-d
6.77
6.78
6.79
6.98
6.99
7.12
7.14
7.15
7.17
7.27
7.38
8.46
8.47
nitrogen atmosphere. The mixture was stirred at 130 °C for 24 h. After cooling to ambient
temperature, the reaction mixture was extracted with EtOAc (3 x 3 mL). The combined organic
layers were dried with Na2SO4 and concentrated in vacuo. The residue was purified on a silica
gel column with petroleum ether as the eluent to afford deuterated product [D1]-1c in (240 mg,
80%). 1H NMR analysis showed >99% deuterium incorporation in the ortho-position.
1H NMR of [D1]-1c
2.3 General Procedure for the Nickel-Catalyzed N-Alkenylation of Anilines
To an oven-dried 10 mL screw-capped vial, aniline 1 (0.5 mmol), vinyl bromide 2 (0.75
mmol), NiCl2 (2 mol%), LitOBu (1.2 equiv) and p-cymene (2 mL) were added under a gentle
stream of argon. The mixture was heated at 120 oC for 12 h followed by cooling to room
temperature. The reaction mixture was filtered through a celite pad with several washings with
dichloromethane (3 x 3 mL) and concentrated in vacuo. The residue was purified on a silica gel
column (eluent: pet ether/EtOAc) to afford the desired alkynylated product 3 or 4.
HN2-pym
F D
>99%(D)
4
3. Synthetic Application
3.3 Procedure for the synthesis of 5
To an oven-dried 10 mL screw-capped vial, K3PO4 (0.5 mL, 2 M aqueous) and toluene (1
mL), and the resulting biphasic mixture was sparged with N2 for 1 h. To the solution were added
3i (30 mg, 0.113 mmol, 1 equiv), 4-chloro phenylboronic acid (21 mg, 1.2 equiv) and Pd(PPh3)4
(20 mg, 15 mol%). The resulting mixture was sparged with N2 for 10 min. The vial was sealed
with a Teflon-coated screw-cap and heated at 90 °C for 14 h. The reaction mixture was filtered
through a celite pad with several washings with dichloromethane (3 x 3 mL) and concentrated in
vacuo. The residue was purified on a silica gel column to afford the desired product 5.
3.4 Procedure for the synthesis of 6
To an oven-dried 10 mL screw-capped vial, aniline 3i (0.1 mmol), morpholine 2 (0.15
mmol), Pd2(dba)3 (5 mol%), BINAP (10 mol%), NatOBu (2 equiv) and toluene (1 mL) were
added under a gentle stream of argon. The mixture was stirred at reflux for 12 h followed by
cooling to room temperature. The reaction mixture was filtered through a celite pad with several
washings with dichloromethane (3 x 3 mL) and concentrated in vacuo. The residue was purified
on a silica gel column to afford the desired product 6.
4. Mechanistic Investigation
4.1 Reversibility of N-alkenylation via C-H bond activation
HN2-pym
F DHN
2-pym
F H/D
>99%(D)standard condition
without 2 39%(D)
[D1]-1c
5
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.021.042.011.002.61
CHLOROFORM-d
6.76
6.77
6.78
6.98
6.99
7.09
7.10
7.12
7.16
7.17
7.53
8.43
8.45
8.45
8.46
8.5 8.0 7.5 7.0Chemical Shift (ppm)
1.021.042.011.002.61
CHLOROFORM-d
6.76
6.77
6.78
6.98
7.10
7.11
7.11
7.12
7.12
7.16
7.27
7.53
8.43
8.45
8.45
8.46
To an oven-dried 10 mL screw-capped vial, aniline [D1]-1c (50 mg, 0.26 mmol), NiCl2 (2
mol%), LitOBu (1.2 equiv) and p-cymene or toluene (1 mL) were added under a gentle stream of
argon. The reaction mixture was heated at 120 oC for 12 h followed by cooling to room
temperature. The mixture was filtered through a celite pad with several washings (3 x 3 mL
dichloromethane) and concentrated in vacuo and the starting material ([D1]-1c) showed 39%
ortho-deuteration.
Note: Under the optimal condition, toluene (1 mL) also gave the same yield (~90%) in the N-
vinylation of aniline (1a). Thus, in all the mechanistic experiments (D-studies) toluene was used
as a solvent.
4.2 H/D Scrambling study
standard condition
HN2-pym
F H/DHN
2-pym
F D
>99%(D)70%(D)
PhBr
2a
+
N2-pym
F H/D39%(D)
Ph
[D1]-1c [D1]-3c
HN2-pym
F H/D
39%(D)
6
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
0.981.031.166.250.611.092.001.01
CHLOROFORM-d
5.48
5.51
6.78
7.13
7.15
7.26
7.27
7.29
7.32
7.34
7.47
7.48
8.44
8.44
8.59
8.62
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.031.166.250.611.09
CHLOROFORM-d
6.78
7.12
7.13
7.15
7.26
7.27
7.29
7.32
7.34
7.38
7.39
7.41
7.45
7.47
7.48
To an oven-dried 10 mL screw-capped vial, aniline [D1]-1c (50 mg, 0.26 mmol), 2a (0.39
mmol), NiCl2 (2 mol%), LitOBu (1.2 equiv) and p-cymene or toluene (1 mL) were added under a
gentle stream of argon. The reaction mixture was heated at 120 oC for 4 h followed by cooling to
room temperature. The mixture was filtered through a celite pad with several washings (3 x 3 mL
dichloromethane) and concentrated in vacuo. The residue was purified by column
chromatography. The obtained product [D1]-3c (54% yield) showed 39% ortho-deuteration and
the recovered starting material [D1]-1c 70% ortho-deuteration.
HN2-pym
F H/D
70%(D)
7
1H NMR of [D1]-1c
4.3 Radical trapping experiment
Yield (%)Additive
TEMPO
Ph
Me30%
50%
HN2-pym
standard condition
2-pymN
Me
Ph
MePh
Br (2a)additive (2 equiv) 3g1g
To an oven-dried 5 mL screw-capped vial, 1g (0.3 mmol), 2a (0.36 mmol), TEMPO or
prop-1-en-2-ylbenzene or cyclohexa-1,4-diene (0.9 mmol), NiCl2 (2 mol %), LiOtBu (1.2 equiv.)
and p-cymene (1 mL) were added under argon atm. The reaction mixture was heated at 120 oC
for 12 h and followed by cooling to room temperature. The solution was filtered through a celite
pad and washed with 10 mL of dichloromethane. The filtrate was concentrated in vacuo. The
yield of 3g was determined by 1H NMR.
N2-pym
F H/D
39%(D)
10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
1.011.032.001.002.30
CHLOROFORM-d
6.76
6.77
6.78
6.98
6.99
7.10
7.11
7.12
7.15
7.17
7.46
8.45
8.46
8.5 8.0 7.5 7.0Chemical Shift (ppm)
1.011.032.001.002.30
CHLOROFORM-d
6.77
6.78
6.98
6.99
7.11
7.12
7.14
7.15
7.17
7.27
7.46
8.45
8.46
8
4.4 Intermolecular competition experiment
HN2-pym
HN2-pym
OMe Cl3k (18%)3j (11%)
(3j:3k = 1:1.6)1j 1k
standard condition+
N2-pym
OMe
+
PhN
2-pym
Cl
Ph
PhBr (2a)
2 h
To an oven-dried 5 mL screw-capped vial, benzamides 1j (0.3 mmol), and 1k (0.3
mmol), 2 (0.3 mmol), NiCl2 (2 mol %), LiOtBu (1.2 equiv.), and p-cymene (1 mL) were added
under argon atm. The mixture was heated at 120 oC for 2 h and followed by cooling to room
temperature. The solution was filtered through a celite pad and washed with dichloromethane (3
x 5 mL). The filtrate was concentrated in vacuo. The residue was purified by column
chromatography on silica gel (eluent: pet ether/EtOAc) to afford the alkynylated products 3j and
3k with the isolated yields of 11% and 18% respectively.
4.5 Product distribution study
(a) To an oven-dried 5 mL screw-capped vial, 1a (0.3 mmol), 2 (0.36 mmol), NiCl2 (2 mol
%), LiOtBu (1.2 equiv.), and p-cymene or toluene (1 mL) were added under argon atm. The
reaction mixture was heated at 120 oC for 12 h and followed by cooling to room temperature.
The solution was filtered through a celite pad and washed with 10 mL of dichloromethane. The
filtrate was concentrated in vacuo. The filtrate was concentrated. The products were analyzed by
GC and GC-MS and no formation of self dimer product (7) was observed.
HN2-pym
Br
LiOtBu, p-cymene, 12 h3a
PhPh
88%
2 mol% NiCl2+
7 (0%)
1a 2a
9
(b) To an oven-dried 5 mL screw-capped vial, 1a (0.3 mmol), 2 (0.36 mmol), Ni(COD)2 (2
mol %), LiOtBu (1.2 equiv.) and p-cymene or toluene (1 mL) were added under argon atm. The
reaction mixture was heated at 120 oC for 12 h and followed by cooling to room temperature.
The solution was filtered through a celite pad and washed with 10 mL of dichloromethane. The
filtrate was concentrated in vacuo. The filtrate was concentrated. The products were analyzed by
GC and GC-MS. A formation of self dimer product (7) in 15% was observed.
HN2-pym
Br
LiOtBu, p-cymene, 12 h3a
PhPh
75%
2 mol% Ni(COD)2+
7 (15%)
1a 2a
4.6 Reaction profile for the Nickel-catalyzed N-alkenylation
To an oven-dried 10 mL screw-capped vial, aniline 1a (0.2 mmol), (E)-(2-
bromovinyl)benzene 2a (0.3 mmol), NiCl2 (2 mol%), LitOBu (1.2 equiv), n-decane as internal
standard and p-cymene (1 mL) were added under a gentle stream of argon. The mixture was
heated at 120 oC and a periodic aliquot was removed and analyzed by GC.
4.7 Identification of C-H bond activated intermediate
HN
N
N std.conditions2a N
N
N
Ph
1j 3j, 76%reflux
A
MeO
HN
N
N
NiMeO
2 MeO
NiCl21 h
To an oven-dried 10 mL screw-capped vial, aniline 1j (0.2 mmol), LitOBu (1.2 equiv),
NiCl2 (2 mol%), and p-cymene (1 mL) were added under a gentle stream of argon. The mixture
was heated at 120 oC and after 1 h an aliquot was removed and analyzed by HRMS (EI). The
observed m/z value is 459.1074 {[M+H] C22H21O2N6Ni}.
10
An alternative mechanism would involve the insertion of an alkene into a N-Ni bond, C-C bond
rotation, the elimination of Ni(II), and isomerization to the more thermodynamically stable trans-
isomer cann’t be rolled out. Indeed, we didn’t detect the formation of a cis-isomer when the
reaction was stopped at a shorter reaction time.
H
Ph
Br
H
NiX NPy Ar
H
Ph
H
N
NiX Br
Py
ArNi(II)
H
Ph
H
NPy
Ar
H
Ph
N
H
Py
Ar
isomerizationC-C bondrotation elimination
11
5. Characterization Data
(E)-N-phenyl-N-styrylpyrimidin-2-amine (3a)
N N
N
21 mg, 80% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). Orange solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.64 (d, J = 14.9 Hz, 1 H), 8.43 (br s, 2 H), 7.59 (br s, 2 H), 7.48 (br s, 1
H), 7.36 - 7.29 (m, 4 H), 7.13 (br s, 1 H), 6.76 (br s, 1 H), 5.43 (d, J = 14.5 Hz, 1 H). 13C NMR
(126 MHz, CHLOROFORM-d) = 159.8, 157.8, 140.0, 137.5, 130.5, 129.9, 129.3, 128.5,
127.9, 125.6, 125.2, 113.0, 111.0. HRMS (EI): m/z Calcd for [M+H] C18H16N3: 274.1344;
Found: 274.1339.
(E)-N-(2-methoxyphenyl)-N-styrylpyrimidin-2-amine (3b)
N N
N
MeO
18 mg, 60% isolated yield. Rf = 0.32 (hexane/EtOAc = 10/1). Yellow liquid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.65 (d, J = 14.5 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 7.52 - 7.42 (m, 1
H), 7.37 - 7.22 (m, 6 H), 7.21 - 7.09 (m, 3 H), 6.75 (t, J = 4.8 Hz, 1 H), 5.44 (d, J = 14.5 Hz, 1
H), 3.78 (s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.6, 157.8, 155.7, 137.7,
130.6, 129.7, 129.5, 128.4, 128.3, 125.4, 125.2, 121.4, 112.9, 112.7, 109.7, 55.8. HRMS (EI):
m/z Calcd for [M+H] C19H18ON3: 304.1450; Found: 304.1444.
12
(E)-N-(2-fluorophenyl)-N-styrylpyrimidin-2-amine (3c)
N N
N
F
25 mg, 88% isolated yield. Rf = 0.32 (hexane/EtOAc = 10/1). Yellow Liquid. 1H NMR (500
MHz, CHLOROFORM-d) = 8.62 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 5.0 Hz, 2 H), 7.52 - 7.45
(m, 1 H), 7.44 - 7.38 (m, 1 H), 7.38 - 7.25 (m, 6 H), 7.18 - 7.12 (m, 1 H), 6.79 (t, J = 4.8 Hz, 1
H), 5.51 (d, J = 14.5 Hz, 1 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.9, 159.3,
158.0, 157.9, 137.3, 131.3, 129.9, 129.9, 129.4, 128.5, 127.5, 127.4, 125.8, 125.4, 125.2, 125.2,
117.2, 117.0, 113.6, 110.6. HRMS (EI): m/z Calcd for [M+H] C8H15FN3: 292.1250; Found:
292.1245.
(E)-N-styryl-N-(3-(trifluoromethyl)phenyl)pyrimidin-2-amine (3d)
N N
N
F3C
26 mg, 75% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.61 (d, J = 14.9 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 7.77 - 7.67 (m, 2
H), 7.62 (s, 1 H), 7.54 (d, J = 7.6 Hz, 1 H), 7.35 - 7.22 (m, 4 H), 7.22 - 7.10 (m, 1 H), 6.80 (t, J =
4.8 Hz, 1 H), 5.42 (d, J = 14.5 Hz, 1 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.6,
157.9, 140.7, 137.1, 133.1, 132.5, 132.3, 130.5, 130.2, 128.6, 126.7, 126.6, 125.9, 125.3, 124.8,
124.7, 124.7, 122.6, 113.6, 111.4. HRMS (EI): m/z Calcd for [M+H] C19H15F3N3: 342.1218;
Found: 342.1213.
13
(E)-N-(3-fluorophenyl)-N-styrylpyrimidin-2-amine (3e)
N N
N
F
23 mg, 78% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.59 (d, J = 14.9 Hz, 1 H), 8.44 (d, J = 5.0 Hz, 2 H), 7.59 - 7.48 (m, 1
H), 7.38 - 7.27 (m, 4 H), 7.24 - 7.12 (m, 3 H), 7.08 (d, J = 9.5 Hz, 1 H), 6.78 (t, J = 4.8 Hz, 1 H),
5.49 (d, J = 14.9 Hz, 1 H). 13C NMR (126 MHz, CHLOROFORM-d) = 164.4, 162.5, 159.6,
157.9, 141.6, 141.5, 137.2, 131.0, 130.9, 130.1, 128.5, 125.8, 125.3, 125.2, 125.1, 117.0, 116.8,
115.2, 115.0, 113.3, 111.3. HRMS (EI): m/z Calcd for [M+H] C18H15FN3: 292.1250; Found:
292.1245.
(E)-3-(pyrimidin-2-yl(styryl)amino)benzonitrile (3f)
N N
N
NC
19 mg, 65% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.56 (d, J = 14.9 Hz, 1 H), 8.43 (d, J = 5.0 Hz, 2 H), 7.75 (d, J = 7.6 Hz,
1 H), 7.72 - 7.62 (m, 2 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.34 - 7.26 (m, 5 H), 7.19 - 7.12 (m, 1 H),
6.83 (t, J = 4.8 Hz, 1 H), 5.41 (d, J = 14.5 Hz, 1 H). 13C NMR (126 MHz, CHLOROFORM-d)
= 159.4, 157.9, 141.1, 136.8, 134.5, 133.4, 131.4, 130.9, 130.0, 128.6, 126.1, 125.3, 118.0,
114.1, 113.8, 111.7. HRMS (EI): m/z Calcd for [M+H] C19H15N4: 299.1297; Found: 299.1291.
14
(E)-N-styryl-N-m-tolylpyrimidin-2-amine (3g)
N N
N
Me
26 mg, 90% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.63 (d, J = 14.5 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 7.47 (s, 1 H), 7.35 -
7.25 (m, 6 H), 7.18 - 7.04 (m, 3 H), 6.75 (t, J = 4.8 Hz, 1 H), 5.44 (d, J = 14.5 Hz, 1 H), 2.46 (s,
3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.9, 157.9, 139.9, 139.9, 137.6, 130.5,
129.8, 129.7, 128.8, 128.5, 126.2, 125.5, 125.2, 112.9, 110.9, 21.5. HRMS (EI): m/z Calcd for
[M+H] C19H18N3: 288.1501; Found: 288.1495.
(E)-N-(3-chlorophenyl)-N-styrylpyrimidin-2-amine (3h)
N N
N
Cl
27 mg, 88% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.60 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 4.6 Hz, 2 H), 7.60 - 7.42 (m, 2
H), 7.41 - 7.23 (m, 6 H), 7.21 - 7.12 (m, 1 H), 6.80 (t, J = 4.8 Hz, 1 H), 5.49 (d, J = 14.9 Hz, 1
H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.6, 157.9, 141.2, 137.2, 135.2, 130.8,
130.1, 129.8, 128.5, 128.2, 127.7, 125.8, 125.3, 113.4, 111.4, 77.3, 76.7. HRMS (EI): m/z Calcd
for [M+H] C18H15N3Cl: 308.0955; Found: 308.0949.
15
(E)-N-(4-bromophenyl)-N-styrylpyrimidin-2-amine (3i)
N N
N
Br
28 mg, 80% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.60 (d, J = 14.5 Hz, 1 H), 8.44 (d, J = 5.0 Hz, 2 H), 7.71 (d, J = 8.4 Hz,
2 H), 7.40 - 7.25 (m, 5 H), 7.22 (d, J = 8.4 Hz, 2 H), 7.20 - 7.11 (m, 1 H), 6.78 (t, J = 4.8 Hz, 1
H), 5.47 (d, J = 14.5 Hz, 1 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.6, 157.8,
139.1, 137.2, 133.2, 131.1, 130.2, 128.5, 125.8, 125.2, 121.7, 113.3, 111.2, 77.3, 76.7. HRMS
(EI): m/z Calcd for [M+H] C18H15N3Br: 352.0449; Found: 352.0444.
(E)-N-(4-methoxyphenyl)-N-styrylpyrimidin-2-amine (3j)
N N
N
OMe
26 mg, 85% isolated yield. Rf = 0.32 (hexane/EtOAc = 4/1). Yellow liqiud. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.69 (d, J = 14.5 Hz, 1 H), 8.46 (d, J = 5.0 Hz, 2 H), 7.42 - 7.20 (m, 7
H), 7.20 - 7.05 (m, 3 H), 6.76 (s, 1 H), 5.48 (d, J = 14.5 Hz, 1 H), 3.92 (s, 3 H). 13C NMR (126
MHz, CHLOROFORM-d) = 160.0, 158.8, 157.8, 137.6, 132.5, 130.7, 130.2, 128.4, 125.5,
125.2, 115.2, 112.9, 110.7, 55.3. HRMS (EI): m/z Calcd for [M+H] C19H18ON3: 304.1450;
Found: 304.1444.
16
(E)-N-(4-chlorophenyl)-N-styrylpyrimidin-2-amine (3k)
N N
N
Cl
28 mg, 90% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.61 (d, J = 14.9 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 7.55 (d, J = 8.8 Hz,
2 H), 7.38 - 7.22 (m, 7 H), 7.22 - 7.07 (m, 1 H), 6.78 (t, J = 4.8 Hz, 1 H), 5.46 (d, J = 14.5 Hz, 1
H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.6, 157.9, 138.6, 137.2, 133.6, 130.8,
130.3, 130.2, 128.5, 125.8, 125.2, 113.3, 111.2. HRMS (EI): m/z Calcd for [M+H] C18H15N3Cl:
308.0955; Found: 308.0949.
(E)-N-(naphthalen-1-yl)-N-styrylpyrimidin-2-amine (3l)
N N
N
24 mg, 75% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.93 (d, J = 14.5 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 8.03 (t, J = 8.2 Hz,
2 H), 7.79 - 7.63 (m, 2 H), 7.61 - 7.50 (m, 2 H), 7.50 - 7.43 (m, 1 H), 7.33 - 7.22 (m, 4 H), 7.19 -
7.06 (m, 1 H), 6.76 (t, J = 4.8 Hz, 1 H), 5.33 (d, J = 14.5 Hz, 1 H). 13C NMR (126 MHz,
CHLOROFORM-d) = 160.0, 158.0, 137.5, 136.6, 134.9, 130.5, 130.0, 128.6, 128.6, 128.4,
127.3, 126.9, 126.3, 126.2, 125.5, 125.2, 123.0, 113.1, 110.8. HRMS (EI): m/z Calcd for [M+H]
C22H18N3: 324.1501; Found: 324.1495.
17
(E)-N-(4-bromonaphthalen-1-yl)-N-styrylpyrimidin-2-amine (3m)
N N
N
Br
28 mg, 70% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.84 (d, J = 1.9 Hz, 3 H), 8.87 (d, J = 1.5 Hz, 3 H), 8.47 - 8.33 (m, 17
H), 8.00 (d, J = 7.6 Hz, 6 H), 7.74 - 7.61 (m, 12 H), 7.55 - 7.44 (m, 7 H), 7.38 (d, J = 7.6 Hz, 7
H), 7.32 - 7.21 (m, 26 H), 7.19 - 7.01 (m, 7 H), 6.78 (t, J = 4.6 Hz, 7 H), 5.29 (d, J = 14.5 Hz, 6
H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.9, 158.0, 137.2, 136.6, 133.4, 131.7,
130.3, 129.9, 128.5, 128.0, 127.8, 127.7, 125.7, 125.2, 123.6, 123.2, 113.3, 111.1. HRMS (EI):
m/z Calcd for [M+H] C22H17N3Br: 402.0606; Found: 402.0600.
(E)-N-(2,3-dimethylphenyl)-N-styrylpyrimidin-2-amine (3n)
N N
N
Me
Me
20 mg, 65% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.67 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 4.6 Hz, 2 H), 7.39 - 7.19 (m, 6
H), 7.18 - 7.04 (m, 2 H), 6.75 (t, J = 4.8 Hz, 1 H), 5.30 (d, J = 14.5 Hz, 1 H), 2.41 (s, 3 H), 2.03
(s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.5, 158.0, 138.5, 138.4, 137.7, 135.3,
129.9, 129.3, 128.5, 126.8, 126.8, 125.5, 125.2, 112.8, 110.120.5, 13.8. HRMS (EI): m/z Calcd
for [M+H] C20H20N3: 302.1657; Found: 302.1652.
18
(E)-N-(3-bromo-4-methylphenyl)-N-styrylpyrimidin-2-amine (3o)
N N
N
BrMe
30 mg, 83% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.61 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 4.6 Hz, 2 H), 7.54 (d, J = 1.9 Hz,
1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.35 (d, J = 7.6 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 2 H), 7.21 (dd, J =
1.9, 8.0 Hz, 1 H), 7.19 - 7.13 (m, 1 H), 6.79 (t, J = 4.8 Hz, 1 H), 5.50 (d, J = 14.5 Hz, 1 H), 2.53
(s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.7, 157.9, 138.6, 137.7, 137.3, 133.0,
131.8, 130.2, 128.5, 128.2, 125.7, 125.4, 125.3, 113.3, 111.2, 22.7. HRMS (EI): m/z Calcd for
[M] C19H16N3Br: 365.0528 Found: 365.0522.
(E)-N-allyl-N-styrylpyrimidin-2-amine (3p)
N N
N
16 mg, 69% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). Yellow liquid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.57 - 8.42 (m, 3 H), 7.42 (d, J = 7.6 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 2 H),
7.19 - 7.10 (m, 1 H), 6.72 (t, J = 4.6 Hz, 1 H), 6.03 - 5.91 (m, 2 H), 5.28 - 5.10 (m, 2 H), 4.87 -
4.69 (m, 2 H). 13C NMR (126 MHz, CHLOROFORM-d) = 158.9, 157.8, 138.0, 132.3, 128.5,
128.1, 125.4, 125.2, 115.9, 112.5, 108.4, 46.2. HRMS (EI): m/z Calcd for [M+H] C15H16N3:
238.1344; Found: 238.1339.
19
(E)-N-pentyl-N-styrylpyrimidin-2-amine (3q)
N N
N
17mg, 63% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). Yellow liquid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.59 - 8.38 (m, 3 H), 7.43 (d, J = 7.2 Hz, 2 H), 7.31 (t, J = 7.6 Hz, 2 H),
7.22 - 7.08 (m, 1 H), 6.69 (t, J = 4.6 Hz, 1 H), 5.97 (d, J = 14.9 Hz, 1 H), 4.10 - 3.96 (m, 2 H),
1.81 - 1.64 (m, 2 H), 1.53 - 1.35 (m, 4 H), 0.96 (t, J = 6.7 Hz, 3 H). 13C NMR (126 MHz,
CHLOROFORM-d) = 159.0, 157.7, 138.3, 128.5, 128.3, 125.3, 125.1, 112.2, 107.3, 43.7, 29.2,
26.0, 22.5, 14.1. HRMS (EI): m/z Calcd for [M+H] C17H22N3: 268.1814; Found: 268.1808.
(E)-N-cyclopentyl-N-styrylpyrimidin-2-amine (3r)
N
NN
19 mg, 73% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). Yellow liquid. 1H NMR (500 MHz,
CHLOROFORM-d) δ ppm 8.44 (d, J = 5.0 Hz, 2 H), 8.15 (s, 1 H), 8.18 (s, 1 H), 7.41 (d, J = 7.6
Hz, 2 H), 7.31 (t, J = 7.6 Hz, 2 H), 7.06 - 7.18 (m, 1 H), 6.68 (t, J = 4.6 Hz, 1 H), 6.18 (s, 1 H),
6.21 (s, 1 H), 5.34 (t, J = 9.0 Hz, 1 H), 2.26 (dd, J = 11.6, 8.2 Hz, 2 H), 1.86 - 2.05 (m, 4 H), 1.63
- 1.80 (m, 2 H). 13C NMR (126 MHz, CHLOROFORM-d) d = 160.0, 157.4, 138.3, 128.5, 128.2,
125.4, 125.1, 112.1, 110.5, 56.5, 27.3, 25.3. HRMS (EI): m/z Calcd for [M+H] C17H20N3:
266.1657; Found: 266.1652
20
(S)(E)-N-(1-phenylethyl)-N-styrylpyrimidin-2-amine (3s)
N N
N
23 mg, 75% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.49 (d, J = 4.6 Hz, 2 H), 8.22 (d, J = 15.3 Hz, 1 H), 7.49 - 7.33 (m, 4
H), 7.33 - 7.20 (m, 5 H), 7.16 - 7.07 (m, 1 H), 6.75 (t, J = 4.8 Hz, 1 H), 6.64 (d, J = 6.9 Hz, 1 H),
5.86 (d, J = 15.3 Hz, 1 H), 1.93 (d, J = 7.2 Hz, 3 H). 13C NMR (126 MHz, CHLOROFORM-d)
= 160.0, 157.7, 141.5, 138.1, 128.4, 128.4, 126.6, 126.4, 126.1, 125.4, 125.1, 112.5, 112.0, 52.1,
15.8. HRMS (EI): m/z Calcd for [M+H] C20H20N3: 302.1657; Found: 302.1652.
(E)-N-styryl-N-(thiophen-2-ylmethyl)pyrimidin-2-amine (3t)
N
NNS
23 mg, 80% isolated yield. Rf = 0.32 (hexane/EtOAc = 3/1). Yellow solid. 1H NMR (500 MHz,
CHLOROFORM-d) δ = 8.54 - 8.40 (m, 3 H), 7.41 (d, J = 7.6 Hz, 2 H), 7.30 (t, J = 7.6 Hz, 2 H),
7.23 - 7.11 (m, 2 H), 7.09 (d, J = 2.7 Hz, 1 H), 6.95 (dd, J = 3.8, 5.0 Hz, 1 H), 6.76 (t, J = 4.8 Hz,
1 H), 6.13 (s, 1 H), 6.16 (s, 1 H), 5.47 (s, 2 H). 13C NMR (126 MHz, CHLOROFORM-d) δ =
158.7, 157.8, 140.1, 137.8, 128.5, 127.8, 126.4, 125.8, 125.5, 125.3, 124.5, 112.9, 108.6, 42.7
HRMS (EI): m/z Calcd for [M+H] C17H16N3S: 294.1065; Found: 294.1059.
21
(E)-N-(pyridin-3-ylmethyl)-N-styrylpyrimidin-2-amine (3u)
N
NN
N
24 mg, 81% isolated yield. Rf = 0.32 (hexane/EtOAc = 3/1). Yellow solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.65 (s, 1 H), 8.59 (s, 1 H), 8.62 (s, 1 H), 8.52 (d, J = 4.2 Hz, 1 H), 8.47
(d, J = 4.6 Hz, 2 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.36 (d, J = 7.6 Hz, 2 H), 7.32 - 7.19 (m, 3 H),
7.19 - 7.10 (m, 1 H), 6.77 (t, J = 4.8 Hz, 1 H), 5.91 (d, J = 14.5 Hz, 1 H), 5.36 (s, 2 H). 13C NMR
(126 MHz, CHLOROFORM-d) = 159.0, 157.9, 148.6, 148.3, 137.4, 134.2, 133.0, 128.5,
127.9, 125.6, 125.2, 123.3, 113.0, 108.7, 45.1. HRMS (EI): m/z Calcd for [M+H] C18H17N4:
289.1453; Found: 289.1449.
(E)-N-(4-fluorostyryl)-N-m-tolylpyrimidin-2-amine (4a)
N N
N
Me
F
19 mg, 63% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). Yellow liquid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.56 (d, J = 14.5 Hz, 1 H), 8.45 (s, 1 H), 8.44 (s, 1 H), 7.49 (t, J = 7.6
Hz, 1 H), 7.34 - 7.23 (m, 3 H), 7.20 - 7.09 (m, 2 H), 6.98 (t, J = 8.8 Hz, 2 H), 6.77 (t, J = 4.6 Hz,
1 H), 5.41 (d, J = 14.5 Hz, 1 H), 2.47 (s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) =
162.1, 160.1, 159.8, 157.9, 139.9, 139.9, 133.7, 133.7, 130.3, 129.8, 129.7, 128.9, 126.5, 126.5,
126.2, 115.4, 115.2, 113.0, 109.8, 21.4. HRMS (EI): m/z Calcd for [M+H] C19H17N3F: 306.1407;
Found: 306.1401.
22
(E)-N-(4-chlorostyryl)-N-m-tolylpyrimidin-2-amine (4b)
N N
N
Me
Cl
21 mg, 65% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.60 (d, J = 14.5 Hz, 1 H), 8.42 (d, J = 4.6 Hz, 2 H), 7.46 (t, J = 7.8 Hz,
1 H), 7.28 (s, 1 H), 7.25 - 7.18 (m, 4 H), 7.14 - 7.06 (m, 2 H), 6.75 (t, J = 4.8 Hz, 1 H), 5.35 (d, J
= 14.5 Hz, 1 H), 2.44 (s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.8, 157.9, 140.0,
139.7, 136.2, 131.0, 130.8, 129.7, 128.9, 128.5, 126.3, 126.1, 113.1, 109.5, 21.5. HRMS (EI):
m/z Calcd for [M+H] C19H17N3Cl: 322.1111; Found: 322.1106.
(E)-N-(2-(biphenyl-4-yl)vinyl)-N-m-tolylpyrimidin-2-amine (4c)
N N
N
Me
Ph
29 mg, 80% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.71 (d, J = 14.5 Hz, 1 H), 8.45 (br. s., 2 H), 7.71 - 7.58 (m, 2 H), 7.58 -
7.37 (m, 7 H), 7.37 - 7.22 (m, 2 H), 7.16 (br. s., 2 H), 6.76 (br. s., 1 H), 5.49 (d, J = 14.5 Hz, 1
H), 2.47 (br. s., 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.8, 157.8, 140.9, 139.9,
138.1, 136.8, 130.6, 129.8, 129.7, 128.8, 128.7, 127.1, 126.9, 126.7, 126.2, 125.6, 113.0, 110.4,
21.4. HRMS (EI): m/z Calcd for [M+H] C25H22N3: 364.1814; Found: 364.1808.
23
(E)-N-(4-isopropylstyryl)-N-m-tolylpyrimidin-2-amine (4d)
N N
N
Me
Me
Me
23 mg, 70% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.60 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 5.0 Hz, 2 H), 7.48 (s, 1 H), 7.36 -
7.22 (m, 3 H), 7.22 - 7.09 (m, 4 H), 6.75 (t, J = 4.8 Hz, 1 H), 5.46 (d, J = 14.5 Hz, 1 H), 2.90 (s,
1 H), 2.47 (s, 3 H), 1.27 (d, J = 6.9 Hz, 7 H). 13C NMR (126 MHz, CHLOROFORM-d) =
159.9, 157.8, 146.3, 140.0, 139.8, 135.1, 129.9, 129.8, 129.6, 128.7, 126.5, 126.2, 125.2, 112.8,
111.0, 33.7, 24.0, 21.4. HRMS (EI): m/z Calcd for [M+H] C22H24N3: 330.1970; Found:
330.1965.
(E)-N-(3-chlorostyryl)-N-m-tolylpyrimidin-2-amine (4e)
N N
N
Me
Cl
23 mg, 73% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.66 (d, J = 14.5 Hz, 1 H), 8.45 (br s, 2 H), 7.48 (br s, 1 H), 7.37 - 7.26
(m, 3 H), 7.18 (br s, 3 H), 7.12 (br s, 3 H), 6.78 (br s, 1 H), 5.35 (d, J = 14.1 Hz, 1 H), 2.46 (br s,
3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.8, 157.9, 140.0, 139.7, 139.6, 134.4,
131.6, 129.8, 129.7, 129.6, 129.0, 126.1, 125.3, 125.0, 123.3, 113.3, 109.3, 21.4. HRMS (EI):
m/z Calcd for [M+H] C19H17N3Cl: 322.1111; Found: 322.1106.
24
(E)-N-(2-(naphthalen-2-yl)vinyl)-N-m-tolylpyrimidin-2-amine (4f)
N N
N
Me
28 mg, 83% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.62 (d, J = 14.1 Hz, 1 H), 8.45 (d, J = 4.6 Hz, 2 H), 7.80 (d, J = 8.4 Hz,
1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.71 (dd, J = 4.8, 7.4 Hz, 2 H), 7.54 (t, J = 8.0 Hz, 1 H), 7.51 -
7.39 (m, 3 H), 7.33 (d, J = 7.6 Hz, 1 H), 7.26 (br s, 2 H), 6.76 (t, J = 4.8 Hz, 1 H), 6.19 (d, J =
14.1 Hz, 1 H), 2.50 (s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.9, 157.9, 140.2,
140.0, 134.9, 133.7, 132.5, 131.2, 129.8, 129.8, 128.9, 128.4, 126.3, 126.1, 125.7, 125.5, 125.4,
123.8, 122.3, 113.0, 108.0, 21.5. HRMS (EI): m/z Calcd for [M+H] C23H20N3: 338.1657; Found:
338.1652.
(E)-N-(3-bromo-4-fluorostyryl)-N-m-tolylpyrimidin-2-amine (4g)
N N
N
Me
FBr
23 mg, 60% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.55 (d, J = 14.5 Hz, 1 H), 8.43 (d, J = 4.6 Hz, 2 H), 7.49 - 7.41 (m, 2
H), 7.29 (s, 1 H), 7.23 - 7.14 (m, 1 H), 7.14 - 7.04 (m, 2 H), 6.99 (t, J = 8.4 Hz, 1 H), 6.77 (t, J =
4.8 Hz, 1 H), 5.30 (d, J = 14.9 Hz, 1 H), 2.44 (s, 3 H). 13C NMR (126 MHz, CHLOROFORM-d)
= 159.7, 158.0, 157.9, 156.1, 140.0, 139.6, 135.5, 135.5, 131.3, 129.8, 129.7, 129.7, 129.0,
126.1, 125.3, 125.3, 116.4, 116.2, 113.2, 109.1, 108.9, 108.2, 21.4. HRMS (EI): m/z Calcd for
[M+H] C19H16N3FBr: 384.0512; Found: 384.0506.
25
(E)-N-(4'-chlorobiphenyl-4-yl)-N-styrylpyrimidin-2-amine (5)
NPh N
N
Cl
39 mg, 90% isolated yield. Rf = 0.32 (hexane/EtOAc = 5/1). White solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.63 (d, J = 14.5 Hz, 1 H), 8.45 (d, J = 4.6 Hz, 2 H), 7.75 (d, J = 8.0 Hz,
2 H), 7.66 - 7.57 (m, J = 8.4 Hz, 2 H), 7.51 - 7.43 (m, J = 8.4 Hz, 2 H), 7.40 (d, J = 8.4 Hz, 2 H),
7.36 - 7.25 (m, 5 H), 7.13 (t, J = 7.1 Hz, 1 H), 6.77 (t, J = 4.6 Hz, 1 H), 5.52 (d, J = 14.5 Hz, 1
H). 13C NMR (126 MHz, CHLOROFORM-d) = 159.8, 157.9, 139.6, 139.4, 138.9, 137.4,
133.6, 130.5, 129.8, 129.0, 128.5, 128.4, 125.7, 125.3, 113.2, 111.3. HRMS (EI): m/z Calcd for
[M+H] C24H19ClN3: 384.1268; Found: 384.1262.
(E)-N-(4-morpholinophenyl)-N-styrylpyrimidin-2-amine (6)
NPh N
N
N
O
27 mg, 80% isolated yield. Rf = 0.32 (hexane/EtOAc = 1/1). Yellow solid. 1H NMR (500 MHz,
CHLOROFORM-d) = 8.66 (d, J = 14.5 Hz, 1 H), 8.44 (d, J = 4.6 Hz, 2 H), 7.35 - 7.30 (m, 2
H), 7.30 - 7.25 (m, 2 H), 7.21 (d, J = 8.8 Hz, 2 H), 7.15 - 7.06 (m, 3 H), 6.74 (t, J = 4.8 Hz, 1 H),
5.48 (d, J = 14.5 Hz, 1 H), 3.95 - 3.89 (m, 4 H), 3.33 - 3.25 (m, 4 H). 13C NMR (126 MHz,
CHLOROFORM-d) = 160.1, 157.8, 150.3, 137.7, 131.6, 130.8, 129.8, 128.4, 125.4, 125.2,
26
116.4, 112.8, 110.7, 66.9, 48.8. HRMS (EI): m/z Calcd for [M+H] C22H23ON4: 359.1872; Found:
359.1866.
6. References
[S1] Ackermann, L.; Lygin, A. V. Org. Lett. 2012, 14, 764.
[S2] Huang, X.; Xu, S.; Tan, Q.; Gao, M.; Lia, M.; Xu, B. Chem. Commun. 2014, 50, 1465
[S3] Tlvekar, V. N.; Arote, N.D.; Herlekar, O. P. Synlett 2005, 16, 2495
27
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
0.941.041.386.431.032.001.950.96
CHLOROFORM-d
5.42
5.44
6.76
7.13
7.27
7.32
7.32
7.48
7.59
8.43
8.63
8.66
7.50 7.25 7.00Chemical Shift (ppm)
1.386.431.032.00
CHLOROFORM-d
7.13
7.27
7.32
7.32
7.48
7.59
7. Spectra
N N
N
3a
28
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
577
.00
77.2
6
110.
9811
3.04
125.
2212
5.58
127.
9212
8.47
129.
3312
9.95
130.
4913
7.51
140.
05
157.
8515
9.83
131 130 129 128 127 126 125Chemical Shift (ppm)
125.
2212
5.58
127.
92
128.
47
129.
33
129.
95
130.
49
N N
N
3a
29
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.271.001.083.265.471.132.041.05
CHLOROFORM-d
3.78
5.42
5.45
6.75
6.76
7.14
7.15
7.16
7.27
7.28
7.30
7.33
7.35
7.48
8.44
8.45
8.63
8.66
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.083.265.471.13
CHLOROFORM-d
6.74
6.75
6.76
7.11
7.12
7.14
7.15
7.16
7.25
7.27
7.28
7.30
7.30
7.32
7.32
7.33
7.35
7.48
7.48N N
N
3b
MeO
30
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
CHLOROFORM-d
55.8
3
76.7
477
.00
77.2
5
109.
6811
2.75
112.
9212
1.42
125.
2512
5.36
128.
3912
9.49
129.
6913
0.62
137.
74
155.
7515
7.85
159.
64
130 125 120 115 110Chemical Shift (ppm)
109.
68
112.
7511
2.92
121.
42
125.
2512
5.36
128.
3412
8.39
129.
4912
9.69
130.
62
N N
N
3b
MeO
31
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
0.891.051.095.941.061.061.850.93
CHLOROFORM-d
5.50
5.52
6.79
6.80
7.15
7.27
7.29
7.30
7.33
7.34
7.35
7.37
7.48
8.45
8.46
8.61
8.64
7.6 7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.095.941.061.06
CHLOROFORM-d
7.13
7.15
7.16
7.27
7.28
7.29
7.30
7.33
7.34
7.35
7.37
7.39
7.40
7.41
7.41
7.47
7.48
7.49
7.49
7.51
N N
N
3c
F
32
200 180 160 140 120 100 80 60 40 20Chemical Shift (ppm)
76.8
377
.08
77.3
4
110.
6011
3.56
117.
0411
7.20
125.
1612
5.19
125.
4112
5.82
128.
5512
9.45
129.
8612
9.92
131.
2813
7.31
157.
9115
8.03
159.
3315
9.91
135 130 125Chemical Shift (ppm)
125.
1612
5.19
125.
4112
5.82
127.
3912
7.48
128.
5512
9.45
129.
8612
9.92
131.
28
137.
31
N N
N
3c
F
33
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.001.021.084.231.000.951.981.961.04
CHLOROFORM-d
5.41
5.44
6.80
6.81
7.15
7.29
7.30
7.32
7.33
7.62
7.71
7.72
7.73
8.43
8.44
8.59
8.62
7.75 7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.021.084.231.000.951.98
CHLOROFORM-d
6.79
6.80
6.81
7.14
7.15
7.17
7.27
7.27
7.29
7.30
7.32
7.33
7.54
7.55
7.62
7.69
7.71
7.72
7.73
7.75
N N
N
3d
F3C
34
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
4111
3.56
122.
6412
4.68
125.
3112
5.91
126.
6512
6.68
128.
5513
0.22
130.
4613
3.08
137.
1114
0.72
157.
9015
9.58
140 135 130 125Chemical Shift (ppm)
122.
6412
4.68
124.
7112
4.81
125.
3112
5.91
126.
6512
6.68
128.
5513
0.22
130.
4613
2.29
132.
5513
3.08
137.
11
140.
72
N N
N
3d
F3C
35
14 13 12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
1.001.161.203.314.141.072.031.05
CHLOROFORM-d
5.47
5.50
6.77
6.78
7.13
7.15
7.27
7.29
7.30
7.32
7.34
7.54
7.55
8.44
8.45
8.58
8.61
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.161.203.314.141.07
CHLOROFORM-d
6.77
6.78
6.79
7.07
7.09
7.13
7.15
7.16
7.17
7.19
7.19
7.27
7.29
7.30
7.32
7.34
7.53
7.54
7.55N N
N
3eF
36
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
2911
3.35
114.
9911
5.15
116.
9612
5.15
125.
1712
5.25
125.
7812
8.50
130.
0813
0.91
130.
9813
7.22
141.
5114
1.60
157.
8715
9.56
162.
4716
4.44
140 135 130 125 120 115Chemical Shift (ppm)
111.
2911
3.35
115.
1511
6.79
116.
96
125.
1512
5.17
125.
2512
5.78
128.
5013
0.08
130.
9113
0.98
137.
22
141.
5114
1.60
N N
N
3eF
37
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.001.061.234.550.981.980.992.051.03
CHLOROFORM-d
5.40
5.43
6.83
7.16
7.28
7.29
7.30
7.31
7.32
7.66
7.68
7.75
8.43
8.44
8.54
8.57
7.75 7.50 7.25Chemical Shift (ppm)
1.234.550.981.980.99
CHLOROFORM-d
7.16
7.17
7.27
7.28
7.29
7.30
7.31
7.32
7.59
7.61
7.66
7.67
7.68
7.70
7.75
7.76
N N
N
3fNC
38
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
7211
3.80
114.
1311
8.05
125.
3112
6.07
128.
5713
0.01
130.
8613
1.40
133.
4313
4.49
136.
8214
1.13
157.
9315
9.38
140 135 130 125 120 115 110Chemical Shift (ppm)
111.
72
113.
8011
4.13
118.
05
125.
3112
6.07
128.
5713
0.01
130.
8613
1.40
133.
4313
4.49
136.
82
141.
13N N
N
3fNC
39
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.101.001.043.105.461.131.951.05
CHLOROFORM-d
1.62
2.46
5.42
5.45
6.75
6.76
7.12
7.13
7.27
7.28
7.29
7.32
7.33
7.47
8.43
8.44
8.62
8.65
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.043.105.461.13
CHLOROFORM-d
6.74
6.75
6.76
7.12
7.13
7.25
7.27
7.28
7.29
7.32
7.33
7.47N N
N
3gMe
40
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
6
76.7
577
.00
77.2
6
110.
9111
2.95
125.
2212
5.53
126.
2012
8.47
128.
8312
9.70
129.
8113
0.54
137.
6113
9.89
157.
8615
9.89
140 135 130 125Chemical Shift (ppm)
125.
2212
5.53
126.
2012
8.47
128.
8312
9.70
129.
8113
0.54
137.
61
139.
8913
9.93
N N
N
3gMe
41
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.001.021.116.202.051.951.03
CHLOROFORM-d
5.48
5.51
6.80
6.81
7.17
7.29
7.30
7.32
7.34
7.36
7.37
7.52
7.53
8.45
8.46
8.59
8.62
7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0Chemical Shift (ppm)
1.116.202.05
CHLOROFORM-d
7.17
7.18
7.25
7.27
7.29
7.30
7.32
7.34
7.36
7.37
7.47
7.48
7.52
7.53
N N
N
3hCl
42
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
577
.00
77.2
6
111.
3611
3.39
125.
2712
5.80
127.
7312
8.20
128.
5112
9.80
130.
1113
0.83
135.
2013
7.19
141.
2515
7.87
159.
55
140 135 130 125Chemical Shift (ppm)
125.
2712
5.80
127.
7312
8.20
128.
5112
9.80
130.
1113
0.83
135.
20
137.
19
141.
25
N N
N
3hCl
43
12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
1.001.051.206.511.951.951.02
CHLOROFORM-d
5.45
5.48
6.78
6.79
7.21
7.23
7.27
7.29
7.30
7.32
7.34
7.70
7.71
8.43
8.44
8.59
8.62
7.75 7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.051.206.511.95
CHLOROFORM-d
6.77
6.78
6.79
7.13
7.15
7.16
7.21
7.23
7.27
7.28
7.29
7.30
7.32
7.34
7.70
7.71
N N
N
Br3i
44
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
2311
3.31
121.
6912
5.23
125.
7712
8.51
130.
1613
1.14
133.
2213
7.20
139.
09
157.
8515
9.56
135 130 125 120Chemical Shift (ppm)
121.
69
125.
2312
5.77
128.
51
130.
1613
1.14
133.
22
137.
20
139.
09
N N
N
Br3i
45
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.000.951.103.216.441.920.99
CHLOROFORM-d
3.92
5.47
5.50
6.76
7.11
7.13
7.25
7.27
7.28
7.29
7.31
7.34
7.36
8.45
8.46
8.68
8.71
7.25 7.00 6.75Chemical Shift (ppm)
1.103.216.44
CHLOROFORM-d
6.76
7.11
7.13
7.15
7.25
7.27
7.28
7.29
7.31
7.34
7.36
N N
N
OMe3j
46
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
55.3
2
76.7
577
.00
77.2
6
110.
6911
2.86
115.
1712
5.18
125.
4712
8.43
130.
1813
0.71
132.
5313
7.58
157.
8015
8.79
159.
99
136 128 120 112Chemical Shift (ppm)
110.
6911
2.86
115.
17
125.
1812
5.47
128.
4313
0.18
130.
7113
2.53
137.
58
N N
N
OMe3j
47
11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
1.001.051.156.191.911.911.05
CHLOROFORM-d
5.44
5.47
6.77
6.78
6.79
7.15
7.27
7.29
7.30
7.32
7.34
7.55
7.56
8.44
8.44
8.60
8.63
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.051.156.191.91
CHLOROFORM-d
6.77
6.78
6.79
7.15
7.16
7.27
7.29
7.30
7.32
7.34
7.55
7.56N N
N
Cl3k
48
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
1911
3.30
125.
2412
5.76
128.
5113
0.23
130.
2613
0.77
133.
6013
7.24
138.
56
157.
8615
9.64
135 130 125 120 115 110Chemical Shift (ppm)
111.
19
113.
30
125.
2412
5.76
128.
5113
0.23
130.
2613
0.77
133.
60
137.
2413
8.56N N
N
Cl3k
49
12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
1.001.081.114.201.132.001.981.951.910.97
CHLOROFORM-d
5.32
5.34
6.77
6.77
7.14
7.27
7.28
7.30
7.31
7.55
7.56
7.71
7.73
8.03
8.05
8.43
8.44
8.91
8.94
9.0 8.5 8.0 7.5 7.0Chemical Shift (ppm)
1.081.114.201.132.001.981.951.910.97
CHLOROFORM-d
6.76
6.77
6.77
7.14
7.27
7.28
7.30
7.31
7.47
7.55
7.56
7.70
7.71
7.73
7.73
7.75
8.02
8.03
8.05
8.43
8.44
8.91
8.94N N
N
3l
50
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
110.
8211
3.06
123.
0412
5.18
125.
5112
6.18
126.
3212
6.86
127.
2812
8.39
128.
63
137.
46
157.
9516
0.02
135 130 125Chemical Shift (ppm)
123.
04
125.
1812
5.51
126.
1812
6.32
126.
8612
7.28
128.
3912
8.56
128.
6313
0.05
130.
46
134.
93
136.
5613
7.46
N N
N
3l
51
13 12 11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
CHLOROFORM-d
5.27
5.30
6.77
6.78
6.79
7.25
7.27
7.29
7.38
7.39
7.99
8.00
8.38
8.40
8.42
8.43
8.84
8.87
8.0 7.5 7.0Chemical Shift (ppm)
CHLOROFORM-d
6.77
6.78
6.79
7.12
7.14
7.24
7.25
7.27
7.29
7.38
7.39
7.48
7.50
7.51
7.64
7.65
7.67
7.70
7.72
7.99
8.00
N N
N
3mBr
52
170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
477
.00
77.2
5
111.
1011
3.34
123.
2312
3.62
125.
2212
5.72
127.
7412
7.81
128.
0112
8.45
129.
8613
0.35
137.
24
158.
0215
9.88
135 130 125Chemical Shift (ppm)
123.
2312
3.62
125.
2212
5.72
127.
7412
7.81
128.
0112
8.45
129.
8613
0.35
131.
68
133.
38
136.
5813
7.24N N
N
3mBr
53
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.822.871.000.951.936.141.850.95
CHLOROFORM-d
2.03
2.41
5.29
5.32
6.75
6.76
7.27
7.29
7.29
7.30
7.30
7.31
7.32
7.34
8.44
8.45
8.66
8.69
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7Chemical Shift (ppm)
0.951.936.14
CHLOROFORM-d
6.74
6.75
6.76
7.08
7.08
7.09
7.10
7.13
7.14
7.25
7.27
7.29
7.29
7.30
7.30
7.31
7.32
7.34N N
N
3n
Me
Me
54
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
13.8
0
20.5
3
76.7
577
.00
77.2
6
110.
1511
2.81
125.
2212
5.47
126.
8112
8.45
129.
3312
9.93
135.
3313
7.72
138.
4313
8.53
158.
0215
9.48
140 138 136 134 132 130 128 126 124Chemical Shift (ppm)
125.
2212
5.47
126.
8112
6.82
128.
4512
9.33
129.
93
135.
33
137.
7213
8.43
138.
53
N N
N
3n
Me
Me
55
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.000.960.981.021.002.102.031.010.861.840.96
2.53
5.49
5.52
6.79
7.16
7.28
7.30
7.31
7.34
7.36
7.45
7.46
7.54
8.45
8.46
8.60
8.63
7.5 7.4 7.3 7.2 7.1Chemical Shift (ppm)
1.021.002.102.031.010.86
7.16
7.17
7.20
7.21
7.22
7.22
7.28
7.30
7.31
7.34
7.36
7.45
7.46
7.54
7.54
N N
N
3o
BrMe
56
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
22.7
4
76.7
577
.00
77.2
6
111.
1911
3.26
125.
2512
5.38
125.
7112
8.20
128.
4813
0.21
131.
8413
3.02
137.
3013
7.67
138.
65
157.
8515
9.65
135 130 125Chemical Shift (ppm)
125.
2512
5.38
125.
7112
8.20
128.
48
130.
21
131.
8413
3.02
137.
3013
7.67
138.
65
N N
N
3o
BrMe
57
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.172.062.011.011.002.092.172.94
CHLOROFORM-d
4.73
4.73
4.74
5.20
5.22
5.23
5.96
5.97
5.99
6.71
6.72
6.73
7.14
7.16
7.29
7.31
7.32
7.41
7.42
8.46
8.47
8.49
8.52
7.25 7.00 6.75Chemical Shift (ppm)
1.011.002.092.17
CHLOROFORM-d
6.71
6.72
6.73
7.13
7.14
7.16
7.27
7.29
7.31
7.32
7.41
7.42
N N
N
3p
58
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
46.2
4
76.7
477
.00
77.2
5
108.
3711
2.53
115.
88
125.
1812
5.40
128.
1112
8.51
132.
3113
7.98
157.
8115
8.91
135 130 125 120 115 110Chemical Shift (ppm)
108.
37
112.
53
115.
88
125.
1812
5.40
128.
1112
8.51
132.
31
137.
98
N N
N
3p
59
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.014.082.382.051.000.970.992.022.042.87
CHLOROFORM-d
0.95
0.96
0.97
1.41
1.42
1.43
1.43
1.44
1.72
1.74
1.75
4.02
4.04
4.05
5.95
5.98
6.68
6.69
6.70
7.13
7.14
7.16
7.30
7.31
7.33
7.42
7.43
8.44
8.45
8.48
7.50 7.25 7.00 6.75Chemical Shift (ppm)
0.970.992.022.04
CHLOROFORM-d
6.68
6.69
6.70
7.13
7.14
7.16
7.27
7.30
7.31
7.33
7.42
7.43
N N
N
3q
60
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
14.0
7
22.5
426
.04
29.2
1
43.7
2
76.7
577
.00
77.2
6
107.
2611
2.20
125.
1212
5.25
128.
2912
8.53
138.
25
157.
6815
9.02
140 135 130 125 120 115 110Chemical Shift (ppm)
107.
26
112.
20
125.
1212
5.25
128.
2912
8.53
138.
25
N N
N
3q
61
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.274.122.060.991.000.981.102.222.160.981.87
CHLOROFORM-d
1.71
1.72
1.73
1.92
1.92
1.93
1.98
1.99
2.25
2.26
5.32
5.34
5.36
6.18
6.21
6.68
6.68
6.69
7.13
7.15
7.16
7.29
7.31
7.32
7.40
7.42
8.15
8.18
8.44
8.45
8.5 8.0 7.5 7.0 6.5Chemical Shift (ppm)
1.000.981.102.222.160.981.87
CHLOROFORM-d
6.21
6.68
6.68
6.69
7.13
7.15
7.16
7.29
7.31
7.32
7.40
7.42
8.15
8.18
8.44
8.45
N
NN
3r
62
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
159.
9915
7.40
138.
27
128.
5112
8.20
125.
4012
5.14
112.
1211
0.50
77.2
577
.00
76.7
4
56.4
6
27.2
825
.35
N
NN
3r
63
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.101.000.980.990.995.074.030.971.86
CHLOROFORM-d
1.92
1.93
5.85
5.88
6.74
6.75
6.76
7.26
7.27
7.28
7.37
7.38
7.39
7.41
8.20
8.23
8.48
8.49
7.25 7.00 6.75Chemical Shift (ppm)
0.980.990.995.074.03
CHLOROFORM-d
6.64
6.65
6.74
6.75
6.76
7.12
7.13
7.13
7.26
7.27
7.28
7.35
7.37
7.38
7.39
7.41
N N
N
3s
64
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
15.8
2
52.0
7
76.7
477
.00
77.2
5
112.
0211
2.48
125.
0612
5.39
126.
1312
6.44
126.
5712
8.39
138.
0514
1.53
157.
7315
9.96
128 127 126 125Chemical Shift (ppm)
125.
06
125.
39
126.
13
126.
4412
6.57
128.
3512
8.39
N N
N
3s
65
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.031.001.010.940.941.932.132.082.83
CHLOROFORM-d
5.47
6.13
6.16
6.76
7.09
7.10
7.15
7.18
7.29
7.30
7.32
7.40
7.42
8.47
8.49
8.50
7.5 7.0 6.5 6.0Chemical Shift (ppm)
1.001.010.940.941.932.132.08
CHLOROFORM-d
6.13
6.16
6.75
6.76
6.77
6.94
6.95
6.95
6.96
7.09
7.10
7.15
7.16
7.18
7.19
7.29
7.30
7.32
7.40
7.42N
NNS
3t
66
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
42.7
1
76.7
577
.00
77.2
6
108.
6411
2.90
124.
5212
5.29
125.
5412
5.84
126.
4412
7.82
128.
5213
7.79
140.
08
157.
8415
8.74
136 128 120 112 104Chemical Shift (ppm)
108.
64
112.
90
124.
5212
5.29
125.
5412
5.84
126.
4412
7.82
128.
52
137.
7914
0.08N
NNS
3t
67
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
2.040.971.001.043.062.110.981.881.000.961.00
CHLOROFORM-d
5.36
5.89
5.92
6.76
6.77
7.14
7.27
7.29
7.30
7.35
7.37
8.46
8.47
8.51
8.52
8.59
8.62
8.65
8.5 8.0 7.5Chemical Shift (ppm)
1.043.062.110.981.881.000.961.00
CHLOROFORM-d
7.14
7.23
7.24
7.27
7.29
7.30
7.35
7.37
7.57
7.58
8.46
8.47
8.51
8.52
8.59
8.62
8.65
N
NN
N3u
68
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
45.0
9
76.7
577
.00
77.2
6
108.
6811
3.02
123.
3512
5.17
125.
6112
7.94
128.
4813
3.01
134.
1613
7.42
148.
2814
8.64
157.
8815
8.97
150 145 140 135 130 125 120 115 110Chemical Shift (ppm)
108.
68
113.
02
123.
3512
5.17
125.
6112
7.94
128.
48
133.
0113
4.16
137.
42
148.
2814
8.64
N
NN
N3u
69
9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.101.001.032.041.993.221.061.181.88
CHLOROFORM-d
2.47
5.40
5.43
6.77
6.96
6.98
6.99
7.14
7.27
7.28
7.29
7.30
7.31
7.49
8.44
8.45
8.54
8.57
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.032.041.993.221.06
CHLOROFORM-d
6.76
6.77
6.78
6.96
6.98
6.99
7.12
7.14
7.27
7.28
7.29
7.30
7.31
7.47
7.49
7.50
N N
N
Me
F
4a
70
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
4
76.7
577
.00
77.2
6
109.
7811
2.97
115.
1911
5.36
126.
1612
6.47
126.
5312
8.86
129.
7212
9.77
130.
3313
3.69
133.
7213
9.92
157.
8515
9.84
160.
1416
2.08
130 125 120 115 110Chemical Shift (ppm)
109.
78
112.
97
115.
1911
5.36
126.
1612
6.47
126.
5312
8.86
129.
7212
9.77
130.
3313
3.69
133.
72
N N
N
Me
F
4a
71
13 12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.171.001.051.964.081.241.061.951.05
CHLOROFORM-d
1.63
2.44
5.34
5.37
6.74
6.75
6.76
7.10
7.22
7.22
7.24
7.27
7.28
7.46
8.42
8.43
8.59
8.62
7.25 7.00 6.75Chemical Shift (ppm)
1.051.964.081.241.06
CHLOROFORM-d
6.74
6.75
6.76
7.09
7.10
7.20
7.20
7.22
7.22
7.23
7.24
7.27
7.28
7.44
7.46
7.47
N N
N
Me
Cl
4b
72
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
5
76.7
577
.00
77.2
6
109.
5011
3.14
126.
1412
6.34
128.
5312
8.93
129.
7413
0.78
130.
9813
6.23
139.
7313
9.97
157.
8815
9.80
138 136 134 132 130 128 126Chemical Shift (ppm)
126.
34
128.
5312
8.93
129.
7413
0.78
130.
98
136.
23
139.
7313
9.97
N N
N
Me
Cl
4b
73
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.000.960.991.9311.371.920.97
CHLOROFORM-d
2.47
5.48
5.51
6.76
7.16
7.41
7.42
7.45
7.47
7.53
7.55
7.62
7.63
8.45
8.70
8.73
7.75 7.50 7.25 7.00 6.75Chemical Shift (ppm)
0.991.9311.37
CHLOROFORM-d
6.76
7.16
7.30
7.32
7.34
7.41
7.42
7.45
7.47
7.49
7.53
7.55
7.62
7.63
N N
N
Me
Ph
4c
74
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
4
76.7
577
.00
77.2
6
110.
4011
2.98
125.
5712
6.19
126.
6812
6.89
127.
1012
8.67
128.
8412
9.79
130.
6313
8.15
139.
8714
0.88
157.
8515
9.83
140 135 130 125Chemical Shift (ppm)
125.
5712
6.19
126.
6812
6.89
127.
1012
8.67
128.
84
129.
7913
0.63
136.
77
138.
15
139.
8714
0.88
N N
N
Me
Ph
4c
75
10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
6.603.071.041.001.054.083.341.071.991.04
CHLOROFORM-d
1.27
1.28
2.47
2.90
5.44
5.47
6.74
6.75
6.76
7.13
7.15
7.17
7.27
7.29
7.30
7.48
8.44
8.45
8.58
8.61
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.054.083.341.07
CHLOROFORM-d
6.74
6.75
6.76
7.13
7.15
7.17
7.27
7.29
7.30
7.48
N N
N
Me4d
Me
Me
76
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
323
.95
33.7
0
76.7
577
.00
77.2
6
111.
0511
2.76
125.
1912
6.20
126.
5012
8.71
129.
6312
9.81
129.
9213
5.09
139.
8014
0.04
146.
3215
7.82
159.
87
145 140 135 130 125Chemical Shift (ppm)
125.
1912
6.20
126.
50
128.
7112
9.63
129.
8112
9.92
135.
09
139.
8014
0.04
146.
32
N N
N
Me4d
Me
Me
77
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.181.001.323.222.372.581.182.151.02
1.66
2.46
5.34
5.37
6.78
7.12
7.18
7.29
7.31
7.48
8.45
8.64
8.67
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.323.222.372.581.18
6.78
7.12
7.18
7.29
7.31
7.48
N N
N
Me4e
Cl
78
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
4
76.7
577
.00
77.2
6
109.
3111
3.26
123.
3012
5.02
125.
2912
6.10
128.
9812
9.61
129.
7013
1.58
134.
3613
9.64
139.
6813
9.99
157.
8815
9.77
135 130 125Chemical Shift (ppm)
123.
30
125.
0212
5.29
126.
10
128.
9812
9.61
129.
7012
9.77
131.
58
134.
36
139.
6413
9.68
139.
99
N N
N
Me4e
Cl
79
11 10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
2.990.941.052.021.043.261.182.032.041.860.96
CHLOROFORM-d
2.50
6.17
6.20
6.76
6.77
7.26
7.44
7.45
7.47
7.54
7.70
7.71
7.72
7.79
7.82
8.45
8.46
8.61
8.64
7.75 7.50 7.25Chemical Shift (ppm)
2.021.043.261.182.032.04
CHLOROFORM-d
7.26
7.27
7.32
7.34
7.41
7.42
7.44
7.45
7.47
7.49
7.52
7.54
7.56
7.70
7.71
7.72
7.72
7.79
7.81
7.82
7.83N N
N
Me4f
80
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
7
76.7
477
.00
77.2
5
108.
0111
3.02
123.
7912
5.43
125.
4812
5.74
126.
1312
6.26
128.
3812
8.90
129.
8113
2.47
139.
9814
0.15
157.
8715
9.92
140 135 130 125Chemical Shift (ppm)
122.
34
123.
7912
5.43
125.
4812
5.74
126.
1312
6.26
128.
3812
8.90
129.
7712
9.81
131.
18
132.
47
133.
71
134.
93
139.
9814
0.15
N N
N
Me4f
81
12 11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
3.191.001.151.012.141.121.372.032.011.07
CHLOROFORM-d
2.44
5.28
5.31
6.76
6.77
6.77
6.99
7.08
7.09
7.27
7.29
7.46
7.47
8.43
8.44
8.53
8.56
7.50 7.25 7.00 6.75Chemical Shift (ppm)
1.151.012.141.121.372.03
CHLOROFORM-d
6.76
6.77
6.77
6.98
6.99
7.01
7.08
7.09
7.17
7.17
7.18
7.18
7.19
7.20
7.20
7.27
7.29
7.44
7.46
7.47
N N
N
Me4g
FBr
82
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
21.4
4
76.7
477
.00
77.2
5
108.
2410
8.89
109.
0611
3.25
116.
1811
6.36
125.
2912
5.34
126.
0712
9.00
129.
6712
9.78
131.
2813
5.50
139.
6114
0.00
157.
8815
8.01
159.
73
140 135 130 125Chemical Shift (ppm)
125.
2912
5.34
126.
07
129.
0012
9.66
129.
6712
9.78
131.
28
135.
4713
5.50
139.
6114
0.00
N N
N
Me4g
FBr
83
11 10 9 8 7 6 5 4 3 2 1 0Chemical Shift (ppm)
1.001.121.328.882.112.062.081.06
CHLOROFORM-d
1.61
5.50
5.53
6.77
6.77
7.13
7.27
7.32
7.39
7.40
7.47
7.61
7.63
7.74
7.76
8.45
8.46
8.62
8.65
7.75 7.50 7.25Chemical Shift (ppm)
1.328.882.112.06
CHLOROFORM-d
7.12
7.13
7.14
7.25
7.27
7.28
7.32
7.34
7.39
7.40
7.45
7.47
7.61
7.63
7.74
7.76
NPh N
N
Cl
5
84
180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
76.7
577
.00
77.2
6
111.
2711
3.20
125.
2712
5.70
128.
4412
8.51
128.
9912
9.75
130.
4613
3.64
137.
4413
9.36
139.
59
157.
9215
9.85
140 135 130 125Chemical Shift (ppm)
125.
2712
5.70
128.
4412
8.51
128.
9912
9.75
130.
46
133.
64
137.
44
138.
8513
9.36
139.
59NPh N
N
Cl
5
85
10 9 8 7 6 5 4 3 2 1Chemical Shift (ppm)
4.154.101.001.033.132.072.222.111.961.01
CHLOROFORM-d
3.28
3.29
3.30
3.91
3.92
3.93
5.47
5.50
6.73
6.74
7.08
7.09
7.12
7.21
7.22
7.27
7.28
7.32
7.33
8.44
8.44
8.64
8.67
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7Chemical Shift (ppm)
1.033.132.072.222.11
CHLOROFORM-d
6.73
6.74
6.75
7.08
7.09
7.12
7.21
7.22
7.25
7.27
7.28
7.32
7.33
NPh N
N
N
O6
86
200 180 160 140 120 100 80 60 40 20 0Chemical Shift (ppm)
CHLOROFORM-d
48.8
2
66.9
0
76.7
577
.00
77.2
6
110.
6811
2.80
116.
3612
5.19
125.
4412
8.44
129.
7913
0.78
131.
6013
7.67
150.
30
157.
8316
0.05
135 130 125 120 115 110Chemical Shift (ppm)
110.
68
112.
80
116.
36
125.
1912
5.44
128.
4412
9.79
130.
7813
1.60
137.
67
NPh N
N
N
O6