AlCl3 catalyzed coupling of: N-benzylic sulfonamides with 2-substituted cyanoacetates through carbon-nitrogen bond cleavage

Article abstract of DOI:10.1039/c7ob01025g

A new cross-coupling reaction of N-benzylic sulfonamides with 2-substituted cyanoacetates for the synthesis of 2-substituted benzylbenzene was reported. In the presence of AlCl₃, a broad range of N-benzylic sulfonamides reacted smoothly with 2-substituted cyanoacetates to afford structurally diverse benzylbenzenes in moderate to excellent yields. The conversion could be enlarged to gram-scale efficiently. The practicability of this approach was further manifested in the synthesis of a related bioactive agent with high anti-inflammatory activity.

Full text of DOI:10.1039/c7ob01025g

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Organic & Biomolecular Chemistry
ARTICLE
AlCl3 Catalyzed Coupling of N-benzylic Sulfonamides with 2-
Substituted Cyanoacetates through Carbon-Nitrogen Bond
Cleavage
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Chen Hu, Gang Hong, Xiaofei Qian, Kwang Rin Kim, Xiaoyan Zhu, and Limin Wang*
www.rsc.org/
A new cross-coupling reaction of N-benzylic sulfonamides with 2-substituted cyanoacetates for the
synthesis of 2-substituted benzylbenzene was reported. In the presence of the AlCl3, a broad range of N-
benzylic sulfonamides reacted smoothly with 2-substituted cyanoacetates to afford structurally diverse
benzylbenzenes in moderate to excellent yields. The conversion could be enlarged to gram-scale efficiently.
The practicability of this approach was further manifested in the synthesis of a related bioactive agent
with high anti-inflammatory activity.
Introduction
The functionalized nitrile derivatives represent an important
class of precursors to amines, carboxylic acids, ketones and
even heterocycles.1 Compounds containing nitrile group,
which are frequently employed as building blocks in drug
discovery programs, play significant roles in biological
activities.2 Due to its adequate possibility of derivatization,
nitriles often appear as key intermediates in total synthesis.3
Till now, over 50 nitriles-containing agents have been reported
in the previous work.4 For example, Zeneca,5 Arensin,6
Milrinone,7 are widely prescribed for the treatment of the
prostate cancer, human aromatase inhibitors, and myocardial
infarction, respectively. Cilomilast, a well-studied nitriles-
containing anti-inflammatory agent, has been widely
prescribed for the treatment of the inflammatory component
of diseases (Figure 1).8
The cleavage of carbon-nitrogen bond or carbon-oxygen bond
under acidic conditions was broadly applied to the formation
of carbon-carbon bond in organic synthesis.9 Owning to the
leaving ability of amino groups,10 sulfonyl-activated primary
benzylic amines (N-benzylic sulfonamides) can generate
benzylic cation with primary sulfonamides as byproducts.11 For
example, the [3+2] cyclization of sulfonyl-activated benzylic
amines with disubstituted alkynes to generate indene
derivatives was developed by Tian and his co-workers in the
presence of a Fe catalyst (Scheme 1, a).9 Meanwhile, they
Figure 1 Selected examples of pharmaceutical agent containing nitriles
accomplished a catalyst-free alkylation of sulfonic acids with
sulfonamides (Scheme 1, b).12 In 2016, our group developed
transition metal-free direct arylation of 2-substituted
cyanoacetates with diaryliodonium salts (Scheme 1, c).4b We
reasoned that 2-substituted cyanoacetates could also react
with sulfonamides to afford structurally diverse nitrile
containing benzylbenzene. Herein, we reported Lewis-acid
catalyzed 2-subsituted cyanoacetates coupling of sulfonamides
via sp3 carbon-nitrogen bond cleavage. And its application to
the simple synthesis of substituted 2-cyanopropanoic amide,
which are useful for the treatment of inflammatory
component of diseases.2a
Results and discussion
Our initial investigation began by employing the ethyl 2-
cyanopropanoate 1a (0.25 mmol) with N-benzhydryl-4-
methybenznesulfonamide 2a (0.3 mmol) as the model substrates to
optimize the reaction condition. To our delight, the expected
product 3a was isolated with 52% yield in presence of AlCl3 (10
mol %) in the 1,2-dichloroethane (1,2-DCE) at 80 oC for 12 h (Table
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Table 1 Optimization of the reaction conditions
View Article Online
DOI: 10.1039/C7OB01025G
time
(h)
Yield
(%)b
Entrya Catalyst (mol %)
Solvent
T (℃)
1
2
AlCl3 (10)
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
CH3CN
1,4-
80
80
80
80
80
80
80
80
80
80
80
12
12
12
12
12
12
12
12
12
12
12
52
21
Yb(OTf)3 (10)
Sc(OTf)3 (10)
Sc(OPF)3 (10)
3
37
4
31
5
La(
P
fb)3 (10)
26
.
6
BF3 OEt2 (10)
40
7
FeCl3 (10)
49
8
TsOH.H2O (10)
AlCl3 (20\50\70)
AlCl3 (100\130)
AlCl3 (100)
35
9c
10
11
53\58\62
68\65
trace
12
AlCl3 (100)
80
12
trace
dioxane
DMSO
DCM
13
14
15
16
17
18
19
20
21
22d
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
AlCl3 (100)
80
80
80
80
80
60
100
80
80
80
12
12
12
12
12
12
12
4
64
65
0
Scheme 1 Summary of previous studies toward sulfonamides and our previous work
EtOH
H2O
0
1, entry 1). Rare earth perfluorooctanoates [Sc(OPF)3] and
pentafluorobenzoates [La(Pfb)3] that developed by our group were
also applied to catalyze the reaction. After a comprehensive
screening, we found that AlCl3 was superior to other rare-earth
metal catalysis, such as Yb(OTf)3, Sc(OTf)3, La(Pfb)3 and Sc(OPF)3
(Table 1, entries 2-5). It was found that a range of different Lewis
CHCl3
90
81
88
82
87
88
CHCl3
CHCl3
CHCl3
CHCl3
8
.
acids such as BF3 OEt2, FeCl3 and TsOH.H2O also worked in this
CHCl3
12
a Reaction conditions: 1a (0.25 mmol), 2a (0.3 mmol), Lewis acid (x mol %), and
solvent (1 mL), at 80 ℃. b Isolated yield. c x mol % of AlCl3. d Under argon.
reaction system, and gave product 3a in 35-49% yield (Table 1,
entries 6-8). Then the amount of AlCl3 was screened. The yield was
increased to 68% by increasing the catalyst loading to 100 mol %
(Table 1, entries 9 and 10). When screening solvents, we cannot
gain the desired products in CH3CN and 1,4 –dioxane (Table 1,
entries 11 and 12). Meanwhile, efforts to enhance yield by replacing
CHCl3 with other solvents such as DMSO, EtOH, H2O and DCM
(Table 1, entries 13-16) proved that the yield gradually decreased,
while CHCl3 had positive effect on the reaction affording the
product in 90% yield (Table 1, entry 17). Subsequently, the
investigation on the effect of temperature showed that this
transformation was most efficiently when conducted at 80 oC (Table
1, entries 17-19). Shortening the reaction time led to the decrease
of the yield (Table 1, entries 20-21). A slightly decrease in the yield
was observed when the reaction was conducted under argon (Table
1, entry 22). So the optimal conditions were determined to be 1a
(0.25 mmol) and N-benzhydryl-4-methybenznesulfonamide 2a (0.30
Substrates
1
containing alkyl group were efficiently coupled
, furnishing
3g in moderate yields of 57-
with N-benzhydryl-4-methybenznesulfonamide
2
a
the corresponding products 3b
-
86%. Among them, when R1 is fluoroalkyl or allyl, 3f and 3e can
be furnished in 60% and 57% yield, respectively. Moreover,
substrates with benzyl and aromatic rings underwent coupling
reaction to give the corresponding products in generally good
yields of 70-84%
(3j-3p). Moreover, H-substituted
cyanoacetate 1q was suitable substrate for this protocol and
generated anticipated product in 70% yield (3q). Cyclic alkyl
substituded cyanoacetates 1h and 1i could not afford the
desired product (3h and 3i).
Next, the reactions of variously substituted N-benzylic
sulfonamides with
1a were examined and the results were
o
listed in Table 2. For substrates bearing either electron-rich
(Me) or electron-deficient (F, Cl, Br) substituents on the
benzene rings of symmetrical N-benzylic sulfonamides, the
coupling reactions performed well and gave desired products
mmol) in the presence of AlCl3 (100 mol %) in CHCl3 (1 mL) at 80 C
for 12 h.
With the optimal reaction conditions in hand, the scope of this
transformation was then explored by employing a variety of 2-
substituted cyanoacetates 1 to react with 2 (Table 2).
with the yields ranging from 84% to 93% (3r, 3s, 3t).
2 | J. Name., 2012, 00, 1-3
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Table 2 Coupling reactions of 2-substituted cyanoacetates
1 with 2
Table 3 Coupling reactions of nitro esters with 2a
View Article Online
DOI: 10.1039/C7OB01025G
Yield
(%)b
Entrya
R1
R2
R3
3
1
2
CH2CH2CH2CH3
CH2CH2CH2Cl
CH(CH3)2
CH2CH=CH2
CH2CH2(CF2)2CF3
CH2CH3
H
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
3b
3c
3d
3e
3f
86
72
80
57
60
62
0
3
H
aReaction conditions:
and CHCl3 (1 mL), at 80 oC. bIsolated yield
4 (0.25 mmol), 2a (0.3 mmol), AlCl3 (100 mol %),
4
H
5
H
.
6
H
3g
3h
3i
7
cyclohexyl
cyclopentane
C6H5CH2
H
Table 4 Coupling reactions of diethyl malonates with 2a
8
H
0
9
H
3j
70
84
81
79
72
77
75
70
93
85
10
11
12
13
14
15
16
17
18
4-BrC6H4CH2
4-FC6H4CH2
4-MeC6H4CH2
4-BrC6H4
H
3k
3l
H
H
3m
3n
3o
3p
3q
3r
3s
H
4-MeC6H4
C6H5
H
H
H
H
C6H5
CH3
CH3
4-F
4-Br
4-
4-FC6H4
4-BrC6H4
aReaction conditions:
and CHCl3 (1 mL), at 80 oC. bIsolated yield
6 (0.25 mmol), 2a (0.3 mmol), AlCl3 (100 mol %),
CH3
CH3
CH3
19
20
21
4-MeC6H4
naphthyl
C6H5
3t
3u
3v
84
72
85
.
Me
4-
Me
4-
Table 5 Coupling reactions of malononitriles with 2a
Me
4-F
4-Br
4-Cl
H
CH3
CH3
CH3
CH3
22
23
24
25
C6H5
C6H5
3w
3x
3y
3z
87
78
79
46
C6H5
naphthyl
2,4,6-
CH3
26
H
3aa
40
triMeC6H2
thienyl
CH3
CH3
CH3
27
28
H
3ab
3ac
trace
trace
4-Br
aReaction conditions: 1a (0.25 mmol), 2 (0.3 mmol), AlCl3 (100 mol %) and
CHCl3 (1 mL) at 80 oC for indicated time. bIsolated yields.
aReaction conditions:
and CHCl3 (1 mL), at 80 oC. bIsolated yield
8 (0.25 mmol), 2a (0.3 mmol), AlCl3 (100 mol %),
Scheme 2 Synthesis of 3a on gram-scale
.
3v
alkyl-substituted sulfonamides were not effective under the
reaction conditions (3ab 3ac).
, 3w, 3x, 3y, 3z, 3aa). However, heteroaryl-substituted and
Meanwhile,
reactions
of
unsymmetrical
N-benzylic
sulfonamides also proceeded smoothly, leading to the efficient
generation of the corresponding products in 40-87% yields (3u
,
,
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by an anti-inflammatory agent. Considering the valuable nitrile
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DOI: 10.1039/C7OB01025G
containing structure, further extension of this process for the
synthesis of structurally diverse nitrile containing compounds
is in progress.
Experimental section
General Information
1H NMR , 13C NMR and 19F NMR spectra were recorded at 400
MHz
,
100 MHz and 376 MHz respectively using
tetramethylsilane as an internal reference. Chemical shifts (δ)
and coupling constants (J) were expressed in parts per million
and hertz, respectively. High-resolution mass spectrometry
(HRMS) was performed on an ESI-TOF spectrometer.
Chemicals were commercially available and used without
purification. Chromatography: Column chromatography was
performed with silica gel (200-300 mesh ASTM). Sulfonamides
compound substrates were prepared according to the
literature procedure.14 Substituted cyanoacetates,15 2-
nitroesters,16 diethyl malonate17 and malononitrile18 were
synthesized according to the reported procedure, respectively.
Typical procedure for N-benzylic sulfonamides with 2-
substituted cyanoacetates
Scheme 3 Application to the improved synthesis of anti-inflammatory agent 13
To test whether the reaction was amenable to scale-up, we
attempted the reaction using 5 mmol of 2-cyanopropanoate
(
(
1a) and 6 mmol of N-benzhydryl-4-methybenznesulfonamide
2a) (Scheme 2). Gratifyingly, the coupling reaction gave the
corresponding product in 81% yield.
Subsequently, 2-nitroesters were reacted with 2a under
4
standard conditions to test the efficiency of this methodology
(Table 3).13 Both alkyl and aryl substituted nitroester
derivatives can proceed smoothly affording the corresponding
2-subsituted cyanoacetates (0.25 mmol, 1 equiv), N-benzylic
sulfonamides (0.3 mmol, 1.2 equiv), AlCl3 (100 mol %), dry
CHCl3 (1 mL) and a stir bar were added to a sealed tube. After
being stirred at 80 oC for indicated time, the mixture was
evaporated under vacuum. The corresponding product was
products in 48%-56% yields (5a
malononitriles and diethyl malonates were also tested under
the standard conditions. The reactions of and aryl
, 5b, 5c). Meanwhile, the
H
isolated by silica gel column chromatography with
dichloromethane/petroleum ether mixture as eluent.
Ethyl 2-cyano-2-methyl-3,3-diphenylpropanoate (3a)
a
substituted diethyl malonate were also found to be compatible
with the reaction and led to the expected products in 60% and
25% yields (7a, 7c) (Table 4). Unfortunately, the methyl-
substituted diethyl malonate could not progress well under the
optimal conditions (Table 4, 7b). Malononitriles bearing alkyl
and aryl substituents were well implemented to form the
Yellow oil, 90% yield. 1H NMR (400 MHz, DMSO-d6) δ 7.58–7.52
(m, 2H), 7.51–7.46 (m, 2H), 7.41–7.26 (m, 6H), 4.51 (s, 1H),
4.03 (q, J = 7.1 Hz, 2H), 1.55 (s, 3H), 0.93 (t, J = 7.1 Hz, 3H); 13
C
NMR (100 MHz, DMSO-d6) δ 168.5, 139.5, 138.0, 129.5, 128.5,
128.4, 128.0, 127.7, 127.4, 119.8, 62.4, 55.8, 48.3, 23.8, 13.4.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C19H19NO2Na
316.1313; Found 316.1310.
desired products (9a, 9b, 9c, 9d) in 52%-94% yield (Table 5).
Further, to demonstrate the utility of this mothod for the
synthesis of medicinally relavant molecules, we targeted a
common intermediate route to the agent 13 with high anti-
inflammatory activity (Scheme 3). The reported routes to
Ethyl 2-benzhydryl-2-cyanohexanoate (3b)
Colorless oil, 86% yield. 1H NMR (400 MHz, CDCl3) δ 7.58–7.58
(m, 4H), 7.38–7.26 (m, 5H), 7.25–7.21 (m, 1H), 4.34 (s, 1H),
4.06 (q, J = 7.1 Hz, 2H), 1.98–1.90 (m, 1H), 1.77–1.67 (m, 1H),
1.30–1.16 (m, 4H), 1.02 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 168.8, 139.3, 138.2, 129.6,
128.8, 128.6, 128.5, 127.8, 127.5, 119.3, 62.7, 57.7, 54.6, 37.6,
27.5, 22.4, 13.8, 13.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H25NO2Na 358.1783; Found 358.1782.
compound 11 involved
a
three-step sequence from
benzaldehyde derivatives.2a The highest yielding route
reported occurs in only 20% yield over three steps. By
employing the mothod reported here with N-benzylic
sulfonamides derivative 10, the target molecular 11 was
formed in 61% yield. This short synthesis was further
highlighted by its modification to the final compound 13 in 36%
overall yield.
Ethyl 2-benzhydryl-4-chloro-2-cyanobutanoate (3c)
Yellow oil, 72% yield. 1H NMR (400 MHz, CDCl3) δ 7.59–7.49 (m,
4H), 7.39–7.26 (m, 5H), 7.26–7.20 (m, 1H), 4.36 (s, 1H), 4.07 (q,
J = 7.1 Hz, 2H), 3.51 (m, 1H), 3.42 (m, 1H), 2.22–2.13 (m, 1H),
2.11–2.01 (m, 1H), 1.84 (q, J = 3.3 Hz, 1H), 1.77–1.63 (m, 1H),
1.02 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.3,
139.0, 137.8, 129.5, 128.9, 128.7, 128.5, 128.0, 127.7, 118.9,
63.0, 57.7, 54.2, 43.7, 35.1, 28.5, 13.7. HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd for C21H22ClNO2Na 378.1237; Found 378.1241.
Ethyl 2-benzhydryl-2-cyano-3-methylbutanoate (3d)
Conclusions
In conclusion, we have demonstrated an efficient coupling
reaction of N-benzylic sulfonamides with 2-substituted
cyanoacetates in the present of AlCl3. The newly developed
protocol features good functional group tolerance, mild
reaction conditions. More importantly, the synthetic utility has
been demonstrated by an improved route to the intermediate
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1
1
Colorless oil, 80% yield. H NMR (400 MHz, CDCl3) δ 7.67–7.58 White solid, 81% yield. H NMR (400 MHz, CDCl3) δ 7.65–7.63
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(m, 2H), 7.54–7.49 (m, 2H), 7.38–7.26 (m, 5H), 7.25–7.16 (m, (m, 2H), 7.58–7.55 (m, 2H), 7.43–7.40 (DmO,I:21H0.)1,0739.3/C67–O7B.207102(m5G,
1H), 4.62 (s, 1H), 4.12–4.02 (m, 2H), 2.29–2.21 (m, 1H), 1.13– 3H), 7.25–7.14 (m, 3H), 6.99–6.91 (m, 2H), 4.53 (s, 1H), 3.96–
1.03 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 167.1, 139.6, 138.5, 3.78 (m, 2H), 3.20 (d, J = 13.5 Hz, 1H), 2.94 (d, J = 13.6 Hz, 1H),
129.3, 129.0, 128.8, 128.6, 127.6, 127.4, 119.9, 62.8, 58.6, 54.1, 0.84 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.0,
34.5, 19.5, 17.2, 13.9. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 163.7, 161.3, 138.9, 137.9, 131.7, 131.6, 129.7, 129.0, 128.7,
C21H23NO2Na 344.1626; Found 344.1624.
128.6, 128.1, 127.7, 118.8, 115.5, 115.3, 62.7, 57.9, 56.4, 42.8,
Ethyl 2-benzhydryl-2-cyanopent-4-enoate (3e)
13.5, 19F NMR (376 MHz, CDCl3) δ -114.47. HRMS (ESI-TOF) m/z:
1
Colorless oil, 57% yield. H NMR (400 MHz, CDCl3) δ 7.58–7.51 [M + Na]+ Calcd for C25H22FNO2Na 410.1532; Found 410.1529.
(m, 4H), 7.39–7.27 (m, 5H), 7.25–7.20 (m, 1H), 5.84–5.69 (m, Ethyl
1H), 5.20–5.13 (m, 2H), 4.39 (s, 1H), 4.05 (q, J = 7.1 Hz, 2H), (3m)
2-cyano-2-(4-methylbenzyl)-3,3-diphenylpropanoate
1
2.70–2.62 (m, 1H), 2.51–2.44 (m, 1H), 1.03 (t, J = 7.1 Hz, 3H); Yellow solid, 79% yield. H NMR (400 MHz, CDCl3) δ 7.69–7.62
13C NMR (100 MHz, CDCl3) δ 168.1, 139.1, 137.9, 130.5, 129.6, (m, 2H), 7.58–7.52 (m, 2H), 7.41-7.35 (m, 2H), 7.33–7.26 (m,
128.9, 128.7, 128.5, 128.0, 127.6, 120.9, 118.8, 62.7, 57.2, 54.5, 3H), 7.24–7.18 (m, 1H), 7.10–7.03 (m, 4H), 4.54 (s, 1H), 4.02–
42.1, 13.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 3.70 (m, 2H), 3.19 (d, J = 13.4 Hz, 1H), 2.93 (d, J = 13.4 Hz, 1H),
C21H21NO2Na 342.1470; Found 342.1469.
Ethyl 2-benzhydryl-2-cyano-5,5,6,6,7,7,8,8,8-nonafluoroocta- δ 168.1, 139.2, 138.1, 137.5, 130.9, 129.8, 129.7, 129.2, 129.0,
2.29 (s, 3H), 0.83 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
noate (3f)
128.7, 128.6, 128.0, 127.6, 118.9, 62.6, 57.9, 56.5, 43.3, 21.2,
1
White solid, 60% yield. H NMR (400 MHz, CDCl3) δ 7.59–7.50 13.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H25NO2Na
(m, 4H), 7.40–7.35 (m, 2H), 7.34–7.29 (m, 3H), 7.27–7.23 (m, 406.1783; Found 406.1790.
1H), 4.37 (s, 1H), 4.08 (q, J = 7.2 Hz, 2H), 2.44–2.23 (m, 2H), Ethyl
2.12–1.94 (m, 2H), 1.01 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, (3n)
2-(4-bromophenyl)-2-cyano-3,3-diphenylpropanoate
CDCl3) δ 167.8, 138.6, 137.3, 129.3, 129.1, 128.8, 128.5, 128.3, White oil, 72% yield. 1H NMR (400 MHz, CDCl3) δ 7.60–7.53 (m,
127.9, 118.1, 63.3, 57.7, 53.7, 28.5, 27.2, 13.3; 19F NMR (376 2H), 7.50–7.39 (m, 4H), 7.38–7.26 (m, 3H), 7.15–7.05 (m, 5H),
MHz, CDCl3) δ -75.14–-84.48 (m, 3F), -114.53 (t, J = 13.6 Hz, 2F), 5.03 (s, 1H), 4.25–3.97 (m, 2H), 1.10 (t, J = 7.1 Hz, 3H); 13C NMR
-124.27 (d, J = 10.2 Hz, 2F), -126.07–-126.15 (m, 2F). HRMS (100 MHz, CDCl3) δ 166.8, 139.2, 137.4, 132.7, 132.0, 129.6,
(ESI-TOF) m/z: [M + Na]+ Calcd for C24H20F9NO2Na 548.1248; 128.8, 128.7, 128.3, 127.7, 127.4, 123.3, 117.9, 63.6, 59.0, 58.0,
Found 548.1243.
Ethyl 2-benzhydryl-2-cyanobutanoate (3g)
Colorless oil, 62% yield. H NMR (400 MHz, CDCl3) δ 7.57–7.50 Ethyl 2-cyano-3,3-diphenyl-2-(p-tolyl)propanoate (3o)
53.5, 29.7, 13.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C24H20BrNO2Na 456.0575; Found 456.0574.
1
1
(m, 4H), 7.36–7.27 (m, 5H), 7.25–7.20 (m, 1H), 4.35 (s, 1H), Yellow solid, 77% yield. H NMR (400 MHz, CDCl3) δ 7.62–7.54
4.07 (q, J = 7.1 Hz, 2H), 2.04–1.95 (m, 1H), 1.84–1.74 (m, 1H), (m, 2H), 7.50–7.43 (m, 2H), 7.36–7.30 (m, 2H), 7.25–7.23 (m,
1.03 (q, J = 7.3 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 168.7, 1H), 7.14–7.04 (m, 7H), 5.08 (s, 1H), 4.20–3.99 (m, 2H), 2.29 (s,
139.4, 138.2, 129.6, 128.8, 128.6, 128.5, 127.8, 127.5, 119.1, 3H), 1.08 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3,
62.7, 57.6, 55.5, 31.5, 13.8, 9.7. HRMS (ESI-TOF) m/z: [M + Na]+ 139.8, 138.8, 137.9, 130.5, 129.7, 129.5, 128.9, 128.6, 128.1,
Calcd for C20H21NO2Na 330.1470; Found 330.1453.
127.5, 127.1, 127.0, 118.4, 68.0, 63.3, 59.1, 57.8, 25.6, 21.0,
Ethyl 2-benzyl-2-cyano-3,3-diphenylpropanoate (3j)
13.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C25H23NO2Na
1
Colorless oil, 70% yield. H NMR (400 MHz, CDCl3) δ 7.69–7.61 392.1626; Found 392.1613.
(m, 2H), 7.59–7.51 (m, 2H), 7.44–7.37 (m, 2H), 7.36–7.25 (m, Ethyl 2-cyano-2,3,3-triphenylpropanoate (3p)
1
5H), 7.25–7.18 (m, 4H), 4.56 (s, 1H), 3.97–3.72 (m, 2H), 3.21 (d, White solid, 75% yield. H NMR (400 MHz, CDCl3) δ 7.55–7.47
J = 13.3 Hz, 1H), 2.97 (d, J = 13.3 Hz, 1H), 0.82 (t, J = 7.1 Hz, 3H); (m, 4H), 7.32–7.24 (m, 2H), 7.23–7.16 (m, 4H), 7.04–6.93 (m,
13C NMR (100 MHz, CDCl3) δ 168.0, 139.1, 138.0, 134.0, 130.0, 5H), 5.01 (s, 1H), 4.22–3.88 (m, 2H), 1.02 (t, J = 7.1 Hz, 3H); 13
C
129.7, 129.0, 128.7, 128.6, 128.5, 128.0, 127.8, 127.6, 118.8, NMR (100 MHz, CDCl3) δ 167.1, 139.7, 137.7, 133.5, 129.8,
62.6, 57.9, 56.4, 43.7, 13.5. HRMS (ESI-TOF) m/z: [M + Na]+ 129.7, 128.9, 128.8, 128.6, 128.4, 128.1, 127.5, 127.2, 127.1,
Calcd for C25H23NO2Na 392.1626; Found 392.1625.
126.5, 118.3, 63.4, 59.4, 58.1, 13.7. HRMS (ESI-TOF) m/z: [M +
Ethyl 2-(4-bromobenzyl)-2-cyano-3,3-diphenylpropanoate (3k) Na]+ Calcd for C24H21NO2Na 378.1470; Found 378.1463.
Yellow oil, 84% yield. 1H NMR (400 MHz, CDCl3) δ 7.67–7.62 (m, Ethyl 2-cyano-3,3-diphenylpropanoate (3q)
2H), 7.57–7.52 (m, 2H), 7.43–7.37 (m, 4H), 7.35–7.27 (m, 3H), Colorless oil, 70% yield. H NMR (400 MHz, CDCl3) δ 7.38–7.28
1
7.25–7.20 (m, 1H), 7.10–7.05 (m, 2H), 4.52 (s, 1H), 4.01–3.78 (m, 8H), 7.27–7.21 (m, 2H), 4.73 (d, J = 8.5 Hz, 1H), 4.23 (d, J =
(m, 2H), 3.18 (d, J = 13.4 Hz, 1H), 2.91 (d, J = 13.4 Hz, 1H), 0.84 8.7 Hz, 1H), 4.13–4.03 (m, 2H), 1.07 (t, J = 7.1 Hz, 3H); 13C NMR
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.9, 138.8, (100 MHz, CDCl3) δ 165.1, 139.4, 138.8, 128.9, 128.8, 128.3,
137.8, 133.1, 131.7, 131.6, 129.7, 129.0, 128.7, 128.6, 128.2, 127.9, 127.8, 127.7, 115.9, 62.9, 51.1, 43.6, 13.8. HRMS (ESI-
127.7, 122.1, 118.6, 62.8, 58.0, 56.2, 42.9, 13.5. HRMS (ESI-TOF) TOF) m/z: [M + Na]+ Calcd for C18H17NNaO2 302.1157; Found
m/z: [M + Na]+ Calcd for C25H22BrNO2Na 470.0732; Found 302.1153.
470.0722.
Ethyl
(3r)
2-cyano-3,3-bis(4-fluorophenyl)-2-methylpropanoate
Ethyl 2-cyano-2-(4-fluorobenzyl)-3,3-diphenylpropanoate (3l)
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1
Colorless oil, 93% yield. H NMR (400 MHz, CDCl3) δ 7.52–7.44 Colorless oil, 78% yield. H NMR (400 MHz, CDCl3) δ 7.51–7.44
View Article Online
DOI: 10.1039/C7OB01025G
(m, 4H), 7.10–6.96 (m, 4H), 4.35 (s, 1H), 4.11 (q, J = 7.1 Hz, 2H), (m, 3H), 7.43–7.34 (m, 4H), 7.34–7.26 (m, 2H), 4.32 (d, J = 1.6
1.59 (s, 3H), 1.08 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) Hz, 1H), 4.10 (dq, J = 14.3, 7.1 Hz, 2H), 1.60 (s, 3H), 1.08 (dt, J =
δ 169.1, 135.0, 134.9, 133.5, 133.4, 131.2, 131.1, 129.9, 119.5, 26.8, 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.2, 138.4,
115.9, 115.8, 115.7, 115.6, 63.1, 55.8, 48.8, 24.4, 13.7, 19F 131.9, 131.2, 130.1, 129.5, 128.9, 128.8, 128.3, 128.1, 127.8,
NMR (376 MHz, CDCl3) δ -114.28, -114.70. HRMS (ESI-TOF) m/z: 121.7, 119.6, 63.1, 56.7, 48.5, 24.4, 13.8. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C19H17F2NO2Na 352.1125; Found 352.1121. [M + Na]+ Calcd for C19H18BrNO2Na 394.0419; Found 394.0414.
Ethyl 3,3-bis(4-bromophenyl)-2-cyano-2-methylpropanoate Ethyl
3-(4-chlorophenyl)-2-cyano-2-methyl-3-phenylpropa-
(3s) noate (3y)
1
Colorless oil, 85% yield. H NMR (400 MHz, CDCl3) δ7.52–7.42 Yellow oil, 79% yield. 1H NMR (400 MHz, CDCl3) δ 7.53–7.43 (m,
(m, 4H), 7.39–7.30 (m, 4H), 4.30 (s, 1H), 4.12 (q, J = 7.2 Hz, 2H), 4H), 7.38–7.23 (m, 5H), 4.34 (d, J = 1.8 Hz, 1H), 4.10 (dq, J =
1.59 (s, 3H), 1.11 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) 14.1, 7.1 Hz, 2H), 1.60 (d, J = 2.4 Hz, 3H), 1.07 (dt, J = 24.9, 7.1
δ 168.9, 137.8, 136.4, 132.1, 131.9, 131.8, 131.1, 130.1, 129.5, Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.1, 130.9, 129.78,
128.9, 122.4, 121.9, 119.3, 63.2, 56.0, 48.3, 24.4, 13.8. HRMS 129.5, 129.0, 128.9, 128.8, 128.3, 128.1, 127.8, 119.6, 63.1,
(ESI-TOF) m/z: [M + Na]+ Calcd for C19H17Br2NO2Na 471.9524; 56.7, 48.6, 24.4, 13.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
Found 471.9521.
C19H18ClNO2Na 350.0924; Found 350.0927.
Ethyl 2-cyano-2-methyl-3,3-di-p-tolylpropanoate (3t)
White solid, 84% yield. H NMR (400 MHz, DMSO-d6) δ 7.42– noate (3z)
Ethyl 2-cyano-2-methyl-3-(naphthalen-2-yl)-3-phenylpropa-
1
1
7.36 (m, 2H), 7.35–7.30 (m, 2H), 7.16 –7.11 (m, 4H), 4.40 (s, Colorless oil, 46% yield. H NMR (400 MHz, CDCl3) δ 8.11–7.95
1H), 4.03 (q, J = 7.1 Hz, 2H), 2.26 (d, J = 9.0 Hz, 6H), 1.53 (s, 3H), (m, 1H), 7.87–7.73 (m, 3H), 7.69–7.45 (m, 5H), 7.44–7.26 (m,
0.97 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 168.6, 3H), 4.54 (d, J = 1.5 Hz, 1H), 4.18–4.01 (m, 2H), 1.66 (d, J = 4.7
136.9, 136.7, 136.5, 135.2, 129.4, 129.0, 127.8, 119.9, 62.4, Hz, 3H), 1.03 (dt, J = 36.6, 7.2 Hz, 3H); 13C NMR (100 MHz,
55.1, 54.8, 48.4, 23.9, 20.5, 20.4, 13.4. HRMS (ESI-TOF) m/z: [M CDCl3) δ 169.4, 129.8, 128.8, 128.7, 128.5, 128.1, 128.0, 127.9,
+ Na]+ Calcd for C21H23NO2Na 344.1626; Found 344.1628.
127.6, 127.1, 126.9, 126.6, 126.4, 126.3, 119.9, 119.8, 63.0,
Ethyl 2-cyano-2-methyl-3-(naphthalen-2-yl)-3-(p-tolyl)propa- 57.5, 48.7, 24.7, 13.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
noate (3u) C23H21NO2Na 366.1470; Found 366.1469.
1
Colorless oil, 72% yield. H NMR (400 MHz, CDCl3) δ 8.07–7.93 Ethyl 2-cyano-3-mesityl-2-methyl-3-phenylpropanoate (3aa)
1
(m, 1H), 7.88–7.71 (m, 3H), 7.70–7.36 (m, 4H), 7.33–7.30 (m, Colorless oil, 40% yield. H NMR (400 MHz, CDCl3) δ 7.24–7.16
1H), 7.26–7.15 (m, 1H), 7.13–7.00 (m, 1H), 4.50 (d, J = 2.7 Hz, (m, 3H), 7.15–7.09 (t, J = 7.0 Hz, 3H), 6.86 (d, J = 2.0 Hz, 1H),
1H), 4.19–4.00 (m, 2H), 2.31 (d, J = 12.1 Hz, 3H), 1.65 (d, J = 7.0 5.40 (s, 1H), 4.40–4.20 (m, 2H), 2.42 (s, 3H), 2.21 (s, 3H), 1.96
Hz, 3H), 1.02 (dt, J = 45.1, 7.1 Hz, 3H); 13C NMR (100 MHz, (s, 3H), 1.42 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 169.5, 139.2, 138.5, 138.3, 137.8, 137.1, 135.6, 130.6, CDCl3) δ 171.1, 140.0, 138.9, 137.2, 132.3, 131.9, 129.3, 128.5,
129.4, 128.6, 127.1, 125.3, 120.0, 119.9, 62.9, 57.3, 48.6, 24.7, 126.8, 126.3, 120.9, 63.5, 48.7, 46.4, 24.7, 22.5, 22.4, 20.8,
21.5, 13.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 14.0. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd forC22H25NNaO2
C24H23NNaO2 380.1626; Found 380.1620.
358.1783; Found 358.1780.
Ethyl 2-cyano-2-methyl-3-phenyl-3-(p-tolyl)propanoate (3v)
Ethyl 2-methyl-2-nitro-3,3-diphenylpropanoate (5a)
1
1
Colorless oil, 85% yield. H NMR (400 MHz, CDCl3) δ 7.56–7.47 Colorless oil, 56% yield. H NMR (400 MHz, CDCl3) δ 7.37–7.33
(m, 2H), 7.44–7.36 (m, 2H), 7.35–7.25 (m, 2H), 7.24–7.17 (m, (m, 4H), 7.32–7.26 (m, 4H), 7.25–7.18 (m, 2H), 5.37 (s, 1H),
1H), 7.12 (dd, J = 21.0, 7.9 Hz, 2H), 4.31 (d, J = 5.3 Hz, 1H), 4.12–4.01 (m, 2H), 1.98 (s, 3H), 1.05 (t, J = 7.1 Hz, 3H); 13C NMR
4.14–4.02 (m, 2H), 2.30 (d, J = 12.3 Hz, 3H), 1.60 (d, J = 3.9 Hz, (100 MHz, CDCl3) δ 166.4, 138.2, 138.1, 129.9, 129.7, 128.5,
3H), 1.13–0.97 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4, 128.4, 127.5, 96.7, 63.0, 56.1, 20.9, 15.7, 13.9, 13.5. HRMS
129.5, 129.4, 129.3, 128.7, 128.6, 128.3, 128.2, 127.8, 127.5, (ESI-TOF) m/z: [M + Na]+ Calcd for C18H19NO4Na 336.1212;
119.9, 62.8, 57.0, 48.8, 29.7, 24.5, 21.0, 13.7. HRMS (ESI-TOF) Found 336.1219.
m/z: [M + Na]+ Calcd for C20H21NO2Na 330.1470; Found Ethyl 2-benzhydryl-2-nitrobutanoate (5b)
330.1471.
Ethyl 2-cyano-3-(4-fluorophenyl)-2-methyl-3-phenylpropa- 1H), 7.44–7.35 (m, 3H), 7.30–7.21 (m, 4H), 7.18–7.13 (m, 2H),
noate (3w)
Yellow oil, 48% yield. 1H NMR (400 MHz, CDCl3) δ 7.77–7.70 (m,
5.04 (s, 1H), 4.22 (q, J = 7.1 Hz, 2H), 4.11–3.95 (m, 2H), 1.25 (d,
1
Colorless oil, 87% yield. H NMR (400 MHz, DMSO-d6) δ 7.63– J = 7.2 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz,
7.50 (m, 3H), 7.49–7.46 (m, 1H), 7.42–7.26 (m, 3H), 7.25– CDCl3) δ 166.4, 138.3, 138.1, 129.9, 129.7, 128.5, 128.4, 127.5,
7.17(m, 2H), 4.56 (d, J = 12.0 Hz, 1H), 4.08–3.98 (m, 2H), 1.55 96.7, 63.0, 56.1, 20.9, 13.5. HRMS (ESI-TOF) m/z: [M + Na]+
(d, J = 3.3 Hz, 3H), 0.95 (dt, J = 14.2, 7.1 Hz, 3H); 13C NMR (100 Calcd for C19H21NNaO4 350.1368; Found 350.1363.
MHz, CDCl3) δ 169.2, 131.3, 130.1, 129.4, 128.9, 128.7, 128.2, Ethyl 2-nitro-2,3,3-triphenylpropanoate (5c)
128.0, 127.7, 115.8, 115.6, 115.4, 63.0, 56.6, 48.8, 29.7, 24.4, Colorless oil, 53% yield. 1H NMR (400 MHz, CDCl3) δ 7.96–7.90
13.8; 19F NMR (376 MHz, CDCl3) δ -113.99. HRMS (ESI-TOF) m/z: (m, 2H), 7.77–7.68 (m, 2H), 7.55–7.44 (m, 4H), 7.42–7.38 (m,
[M + Na]+ Calcd for C19H18FNO2Na 334.1219; Found 334.1215.
2H), 7.34–7.28 (m, 4H), 7.22–7.18 (m, 1H), 5.23 (d, J = 24.0 Hz,
Ethyl 3-(4-bromophenyl)-2-cyano-2-methyl-3-phenylpropa- 1H), 4.37 (q, J = 7.2 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR
noate (3x)
(100 MHz, CDCl3) δ 186.5, 163.9, 137.6, 134.9, 132.5, 132.4,
6 | J. Name., 2012, 00, 1-3
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130.1, 130.0, 128.9, 128.8, 128.5, 128.3, 128.1, 128.0, 62.4, (m, 4H), 7.23–7.16 (m, 1H), 6.97–6.92 (m, 1H), 6.87–6.79 (m,
View Article Online
59.2, 14.1, 14.0. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for 1H), 5.94 (s, 1H), 4.03 (s, 3H), 4.01–3.90 (m, 2H), 1.73 (s, 3H),
DOI: 10.1039/C7OB01025G
C23H21NO4Na 398.1368; Found 398.1359.
0.88 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.5,
Diethyl 2-benzhydrylmalonate (7a)
156.7, 136.8, 134.0, 131.8, 131.0, 130.0, 128.9, 128.0, 126.4,
1
Colorless oil, 60% yield. H NMR (400 MHz, CDCl3) δ 7.25–7.20 126.0, 125.6, 125.0, 123.7, 123.4, 121.1, 120.3, 110.4, 62.6,
(m, 4H), 7.19–7.14 (m, 4H), 7.12–7.04 (m, 2H), 4.67 (d, J = 12.2 55.6, 49.5, 42.6, 24.6, 13.6. HRMS (ESI-TOF) m/z: [M + Na]+
Hz, 1H), 4.25 (d, J = 12.2 Hz, 1H), 3.96–3.85 (m, 4H), 0.93 (t, J = Calcd for C24H23NNaO3 396.1576; Found 396.1578.
7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 167.7, 141.4, 128.6, 2-cyano-3-(2-methoxyphenyl)-2-methyl-3-(naphthalen-1-
127.8, 126.9, 126.6, 61.5, 57.5, 51.2, 13.8. HRMS (ESI-TOF) m/z: yl)propanoic acid (12)
[M + Na]+ Calcd for C20H22NaO4 349.1416; Found 349.1411.
Diethyl 2-benzhydryl-2-phenylmalonate (7c)
White solid, 83% yield. 1H NMR (400 MHz, DMSO-d6) δ 8.13 (d,
J = 7.2 Hz, 1H), 7.93–7.83 (m, 3H), 7.60 (t, J = 7.8 Hz, 1H), 7.49–
Colorless oil, 25% yield. 1H NMR (400 MHz, CDCl3) δ 7.34–7.27 7.43 (m, 2H), 7.25–7.21 (m, 1H), 7.18–7.10 (m, 2H), 6.81 (td, J
(m, 1H), 7.24–7.19 (m, 2H), 7.19–7.13 (m, 3H), 7.12–7.06 (m, = 7.5, 1.2 Hz, 1H), 5.80 (s, 1H), 4.05 (s, 3H), 1.64 (s, 3H); 13C
4H), 7.04–6.99 (m, 5H), 4.51 (d, J = 9.0 Hz, 1H), 4.16–4.03 (m, NMR (100 MHz, DMSO-d6) δ 170.6, 156.6, 136.9, 131.0, 130.0,
4H), 1.15 (t, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 168.3, 129.0, 128.8, 127.7, 126.6, 125.9, 125.0, 122.9, 122.8, 120.6,
168.2, 143.9, 143.7, 130.8, 129.7, 129.5, 129.3, 129.3, 128.6, 120.4, 111.2, 56.0, 48.9, 42.0, 24.2. HRMS (ESI-TOF) m/z: [M +
128.4, 126.4, 61.8, 58.0, 57.6, 56.6, 14.1. HRMS (ESI-TOF) m/z: Na]+ Calcd for C22H19NNaO3 368.1263; Found 368.1263.
[M + Na]+ Calcd for C26H26NaO4 425.1729; Found 425.1725.
3-(2-methoxyphenyl)-2-methyl-3-(naphthalen-1-yl)-2-
2-benzhydrylmalononitrile (9a)
(piperidine-1-carbonyl)propanenitrile (13)
1
1
Colorless oil, 83% yield. H NMR (400 MHz, CDCl3) δ 7.34–7.27 White solid, 70% yield. H NMR (400 MHz, CDCl3) δ 8.11 (d, J =
(m, 5H), 7.25-7.16 (m, 5H), 4.53 (d, J = 8.1 Hz, 1H), 4.32 (d, J = 7.2 Hz, 1H), 7.97–7.87 (m, 1H), 7.71–7.62 (m, 2H), 7.44–7.27
8.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 137.1, 129.3, 128.7, (m, 4H), 7.15–7.07 (m, 1H), 6.85 (dd, J = 8.3, 1.1 Hz, 1H), 6.79–
127.9, 112.0, 51.6, 29.0. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd 6.70 (m, 1H), 5.85 (s, 1H), 3.99–3,89 (m, 4H), 3.84–3.72 (m, 1H),
for C16H12N2Na 255.0898; Found 255.0890.
2-benzhydryl-2-isopropylmalononitrile (9b)
3.03 (t, J = 6.0 Hz, 2H), 1.66 (s, 3H), 1.40–0.99 (m, 6H); 13C NMR
(100 MHz, CDCl3) δ 169.5, 156.7, 136.8, 134.0, 131.7, 130.9,
White oil, 52% yield. 1H NMR (400 MHz, CDCl3) δ 7.53–7.45 (m, 129.1, 128.8, 128.1, 126.5, 125.8, 125.7, 125.1, 123.7, 123.3,
4H), 7.33–7.18 (m, 6H), 4.28 (s, 1H), 2.18–2.10 (m, 1H), 1.17 (d, 121.1, 120.2, 110.4, 65.7, 55.7, 49.8, 44.1, 42.5, 28.5, 25.6,
J = 6.7 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 136.7, 129.1, 129.0, 24.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C27H28N2NaO2
128.5, 114.9, 54.5, 49.4, 33.9, 18.4. HRMS (ESI-TOF) m/z: [M + 435.2048; Found 435.2050.
Na]+ Calcd for C19H18N2Na 297.1368; Found 297.1375.
2-benzhydryl-2-phenylmalononitrile (9c)
White oil, 71% yield. 1H NMR (400 MHz, CDCl3) δ 7.31–7.26 (m,
10H), 7.20–7.17 (m, 5H), 4.44 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 135.3, 130.8, 128.8, 128.1, 128.0, 127.7, 127.4, 125.8, 113.9,
61.3, 46.3. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H16N2Na 331.1211; Found 331.1202.
Acknowledgements
This research was financially supported by the National Nature
Science Foundation of China (21272069, 20672035) and the
Fundamental Research Funds for the Central Universities and
Key Laboratory of Organofluorine Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences.
2-benzhydryl-2-methylmalononitrile (9d)
1
Colorless oil, 94% yield. H NMR (400 MHz, CDCl3) δ 7.58–7.49
(m, 4H), 7.44–7.31 (m, 6H), 4.23 (d, J = 2.7 Hz, 1H), 1.81 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 136.8, 129.12, 128.8, 128.6, 116.1,
58.4, 36.4, 25.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C17H14N2Na 269.1055; Found 269.1062.
Notes and references
1
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Kukushkin and A. J. L. Pombeiro, Inorg. Chim. Acta., 2005, 358
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N-((2-methoxyphenyl)(naphthalen-1-yl)methyl)-4-
methylbenzenesulfonamide (10)
1
White solid, 80% yield. H NMR (400 MHz, CDCl3) δ 7.79–7.72
(m, 1H), 7.69–7.65 (m, 2H), 7.58–7.51 (m, 3H), 7.45–7.39 (m,
2H), 7.35–7.31 (m, 1H), 7.21–7.14 (m, 1H), 7.05–6.99 (m, 3H),
6.82–6.77 (m, 1H), 6.70–6.66 (m, 1H), 5.82 (d, J = 9.1 Hz, 1H),
3.57 (s, 3H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.4,
142.9, 138.0, 137.5, 133.1, 132.5, 129.7, 129.1, 128.1, 127.9,
127.6, 127.5, 127.0, 126.0, 125.9, 125.4, 125.3, 120.7, 111.1,
59.0, 55.3, 21.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C25H23NNaO3S 440.1296; Found 440.1295.
2
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