Cascade reaction of propargylic alcohols with hydroxylamine hydrochloride: facile synthesis of α,β-unsaturated oximes and nitriles

Article abstract of DOI:10.1016/j.tet.2016.09.010

We have developed an easy and practical method for the synthesis of α,β-unsaturated oximes and nitriles from readily available propargylic alcohols with hydroxylamine hydrochloride (NH₂OH·HCl) under metal-free conditions. By using or not using p-toluenesulfonyl chloride (p-TsCl) as the dehydrating promoter, the desired nitriles or oximes could be obtained, respectively via a three-step one-pot or two-step one-pot process in moderate to excellent yields with good functional group compatibility.

Full text of DOI:10.1016/j.tet.2016.09.010

Accepted Manuscript
Cascade reaction of propargylic alcohols with hydroxylamine hydrochloride: facile
synthesis of α,β-unsaturated oximes and nitriles
Qi Zhang, Linjing Zhang, Chaojun Tang, Huan Luo, Xuediao Cai, Yonghai Chai
PII:
S0040-4020(16)30917-6
10.1016/j.tet.2016.09.010
TET 28081
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 30 June 2016
Revised Date: 6 September 2016
Accepted Date: 9 September 2016
Please cite this article as: Zhang Q, Zhang L, Tang C, Luo H, Cai X, Chai Y, Cascade reaction of
propargylic alcohols with hydroxylamine hydrochloride: facile synthesis of α,β-unsaturated oximes and
nitriles, Tetrahedron (2016), doi: 10.1016/j.tet.2016.09.010.
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Graphical Abstract
Cascade reaction of propargylic alcohols
with hydroxylamine hydrochloride: facile
synthesis of α,β-unsaturated oximes and
nitriles
Leave this area blank for abstract info.
Qi Zhanga, * , Linjing Zhanga , Chaojun Tangb , Huan Luo a , Xuediao Caia and Yonghai Chaic, *
aSchool of Chemistry and Chemical Engineering, Shaanxi Normal University
bChongqing Huapont Pharm. CO., LTD
.
cKey Laboratory of Applied Surface and Colloid Chemistry, MOE, Shaanxi Normal University

1
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Tetrahedron
journal homepage: www.elsevier.com
Cascade reaction of propargylic alcohols with hydroxylamine hydrochloride: facile
synthesis of α,β-unsaturated oximes and nitriles
Qi Zhanga, , Linjing Zhanga , Chaojun Tangb , Huan Luoa , Xuediao Caia and Yonghai Chaic,
aSchool of Chemistry and Chemical Engineering, Shaanxi Normal University, No. 199 South Chang’an Road, Xi’an 710062, P. R. of China
bChongqing Huapont Pharm. CO., LTD., No. 69 Xingguang Avenue, Chongqing 401121, P. R. of China
cKey Laboratory of Applied Surface and Colloid Chemistry, MOE, Shaanxi Normal University, No. 199 South Chang’an Road, Xi’an 710062, P. R. of China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We have developed an easy and practical method for the synthesis of α,β-unsaturated oximes
and nitriles from readily available propargylic alcohols with hydroxylamine hydrochloride
(NH2OH HCl) under metal-free conditions. By using or not using p-toluenesulfonyl chloride (p-
TsCl) as the dehydrating promoter, the desired nitriles or oximes could be obtained respectively
via a three-step one-pot or two-step one-pot process in moderate to excellent yields with good
functional group compatibility.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved
.
α,β-unsaturated oximes
α,β-unsaturated nitriles
propargylic alcohols
hydroxylamine hydrochloride
organic acid
dehydrating promoter
also been reported.7 With regard to the synthesis of α,β-
unsaturated nitriles, apart from the strategy of the functional
transformation of other nitrogen-containing compounds (e.g.
oximes, azides, amide, etc),8 this type of compounds can also be
prepared by means of the installation of the cyano group9 or the
formation of the carbon-carbon double bond10. In recent years,
the synthetic approaches to α,β-unsaturated nitriles through a
cascade reaction have also been established.11,12 Among those,
the efficient and atom-economic preparation of α,β-unsaturated
nitriles from readily available propargylic alcohols have attracted
considerable attention.12 The Zhan and Jiao groups have reported
the direct transformation of propargylic alcohols to the desired
nitriles with 4-methylbenzenesulfonohydrazide (TsNHNH2) and
azidotrimethylsilane (TMSN3) as the nitritrogen source
respectively.12b,c Very recently, the Liang group has also
accomplished this transformation by using more stable and
inexpensive NH2OH HCl instead.12a In Liang’s method, 3 equiv
of chlorotrimethylsilane (TMSCl) was employed as the promoter.
1. Introduction
α,β-Unsaturated oximes and nitriles are of significant interests
as intermediates in organic synthesis for diverse functional group
transformations and carbon-carbon/carbon-heteroatom bond
formations due to their bifunctional and dipolar nature.1-3
Furthermore, this type of structures often serves as a core
structural skeleton in
a
variety of natural products,
pharmaceuticals, and other useful materials4,5 such as oxime I4c, a
potential insecticide, and nitile II5b, a tubulin polymerization
inhibitor.
The classical method for the preparation of α,β-unsaturated
oximes lies in the condensation between a corresponding
carbonyl compound and hydroxylamine hydrochloride
(NH2OH HCl) in the presence of a stoichiometric amount of a
base.6 Recently, new protocols, such as the oxidation of primary
amines, the direct conversion of alcohols into oximes, etc, have
———
In view of the significance of unsaturated nitrogen-containing
compounds and encouraged by the above-mentioned work, we
were interested in developing a facile and low-cost protocol for
the nitrogenation of propargylic alcohols. Herein, we reported an
organic acid-catalyzed direct formation of α,β-unsaturated
oximes and nitriles from propargylic alcohols with NH2OH HCl
Corresponding author. Tel.: +86-29-81530782; fax: +86-29-81530783; e-mail: qiqizhang@snnu.edu.cn (Q. Zhang)
Corresponding author. Tel.: +86-29-81530783; fax: +86-29-81530783; e-mail: ychai@snnu.edu.cn (Y. Chai)

2
Tetrahedron
ACCEPTED MANUSCRIPT
as the nitrogen source. With or without the addition of a
dehydrating promoter, nitriles or oximes could be readily
prepared respectively via a three-step one-pot or two-step one-pot
process (Scheme 1).
Entry
Product
Time (h)
Yieldb
1
2
3
4
5
6
7
R = H (2a)
4
96%
75%
81%
80%
87%
81%
86%
R = o-Me (2b)
R = m-Me (2c)
R = p-Me (2d)
R = p-F (2e)
R = p-Cl (2f)
16
3
Scheme 1 This work: Nitrogenation of propargylic alcohols.
2. Results and discussion
2
We initially chose 1,1-diphenylprop-2-yn-1-ol (1a) as the
model substrate to explore the suitable reaction condition for the
transformation of propargylic alcohol to α,β-unsaturated oxime
(Table 1). In the presence of 0.3 equiv of trifluoroacetic acid
(TFA) in DCE, 1a could react with NH2OH HCl, giving the
expected α,β-unsaturated oxime 2a in 13% yield after 12 h at 90
oC along with the α,β-unsaturated nitrile, a further dehydrated
product from 2a (Table 1, entry 1). The yield was slightly
increased when (±)-camphor-10-sulfonic acid ((±)-CSA) was
used instead of TFA, and interestingly, the major side-product is
the α,β-unsaturated aldehyde (Table 1, entry 2). To our delight,
when 0.3 equiv of p-toluenesulfonyl acid (PTSA) was employed
as the catalyst, the reaction time was shortened to 4 h and the
yield of 2a experienced a dramatic upgrade to 96% (Table 1,
entry 3). 4-Toluenesulfonic acid pyridine salt (PPTS), a weaker
organic acid, could not catalyze the cascade reaction and 1a was
recovered almost quantitatively (Table 1, entry 4). Solvents were
proved to have great effect on this transformation. Among
commonly used solvents, DCE was the most effective one (Table
1, entry 5-8). It is noteworthy that all oximes were obtained as a
mixture of two stereoisomers.
6
5
5
OH
N
(2g)
8
9
4
4
57%
39%
OH
N
(2h)
Table 1. Optimization of reaction conditions from 1a and
10
R = H (2j)
4
30%
85%
73%
64%
89%
NH2OH HCla
11c
12c
13c
14
R = H (2j)
3.5
3.5
8
R = p-Me (2k)
R = p-Cl (2l)
5
OMe
N
Entry
Cat.
Solvent
DCE
Time (h)
Yieldb
13%
28%
96%
0%
(2m)
1
2
3
4
5
6
7
8
TFA
12
12
4
15
12
18%
(±)-CSA
PTSA
PPTS
PTSA
PTSA
PTSA
PTSA
DCE
DCE
DCE
12
24
24
48
48
Toluene
MeCN
Dioxane
THF
58%
28%
27%
5%
aUnless otherwise noted, all reactions were performed with 1a (0.2 mmol)
and NH2OH HCl (1.2 equiv) in the presence of PTSA (0.3 equiv) in DCE (1
mL) at 90 oC for an appropriate time.
bYields are given for isolated products.
cThe reactions were performed using a modified procedure: 1a (0.2 mmol),
PTSA (0.3 equiv) and DCE (1 mL) were first stirred at 90 oC for 30 min; then
NH2OH HCl (1.2 equiv) was added to the reaction system and the resulting
mixture was stirred at 90 oC for an appropriate time.
aUnless otherwise noted, all reactions were performed with 1a (0.2 mmol)
and NH2OH HCl (1.2 equiv) in the presence of an organic acid (0.3 equiv) in
solvent (1 mL) at 90 oC.
bYields are given for isolated products.
Next, we examined the substrate scope of the new method
(Table 2). Under the optimal condition, various 1,1-diaryl-
substitued tertiary propargylic alcohols were readily transformed
to the corresponding α,β-unsaturated oximes in moderate to
excellent yields irrespective of the aryl substitution, showing
Table 2. Transformation of propargylic alcohols to α,β-
unsaturated oximesa

3
little electric and/or steric dependence (Table 2, entry 1-8). This
approach was also applicable to the propargaylic alcohols with an
aryl substitute and an alkyl substitute in C-1 position, such as 2-
phenylbut-3-yn-2-ol 1i, but the corresponding oximes were
obtained in relatively low yield (39%). The decrease in the yield
probably resulted from other acid-catalyzed competing reactions
(e.g. Rupe rearrangement and β-elimination) (Table 2, entry 9).
The direct oximation of secondary propargylic alcohol 1j also
occurred, affording the desired oxime 2j in 30% yield (Table 2,
entry 10). To improve the yield, a slightly modified procedure
was employed: propargylic alcohol was first stirred under the
condition of PTSA (0.3 equiv)/DCE/90 oC for 30 min to give the
(Table 3, entry 1). When trifluoroacetic anhydride (TFAA) was
ACCEPTED MANUSCRIPT
used, the reaction became complicated and 3a was only obtained
in 21% yield (Table 3, entry 2). It has been reported that p-
toluenesulfonyl chloride (p-TsCl), a common and cheap reagent,
can also promote the dehydration of oximes in the presence of a
stoichiometric amount of a base, usually NEt3 or pyridine.8h,i
Gratifyingly, when p-TsCl was employed under the acidic
condition, the formation of nitrile also proceeded smoothly,
providing 3a in 68% (Table 3, entry 3). The further investigation
of the amount of the promoter showed that the use of 2 equiv of
p-TsCl was the best choice and gave the expected product in 79%
(Table 3, entry 3-5). Addition of 4Å molecular sieve didn’t lead
to any beneficial effect (Table 3, entry 6).
α,β-unsaturated
aldehyde
through
Meyer-Schuster
rearrangement; then 1.2 equiv of NH2OH HCl was introduced
into the reaction mixture. As a result, 2j was obtained with a
dramatic increase of the yield to 85% (Table 2, entry 11). The
following exploration showed that secondary propargylic
alcohols bearing electron-withdrawing or -donating substituents
on the aryl ring were compatible with this modified procedure,
and produced the desired oximes in moderate to good yields
(Table 2, entry 12-13). When using O-alkylhydroxylamine
hydrochloride (e.g. NH2OMe HCl) as the nitrogen source,
alkenyl O-alkyl oxime could also be prepared successfully (Table
2, entry 14). However, the yield decreased palpably when a
substrate with an alkyl group in C-3 position was used, implying
that the steric hindrance surrounding the oximido group has a
significant effect on this transformation (Table 2, entry 15). In
consistent with the stereo-outcome of 2a (Table 1), all prepared
oximes consist of two stereoisomers.
With the optimal condition in hand, the scope of this
transformation was explored (Table 4). A variety of 1,1-diaryl-
substitued propargylic alcohols were easily converted into the
corresponding α,β-unsaturated nitriles in moderate to good
yields, which indicates that the substituents on the aryl ring have
little electric and/or steric effect (Table 4, entry 1-8). However,
the propargylic alcohol with methyl group at C-1 position led to
complicated mixtures along with the desired product in low yield
probably due to other acid-catalyzed competing reactions (Table
4, entry 9). The cascade reaction of secondary propargylic
alcohols also performed well and gave the (E)-acrylonitriles
selectively via a little changed procedure, introducing p-TsCl and
NH2OH HCl into the reaction system after the completion of the
PTSA-catalyzed Meyer-Schuster rearrangement (Table 4, entry
10-14). In addition, polycyclic aromatic and heteroaromatic
substituted propargylic alcohols were suitable in this
transformation, but the yields of the expected nitriles were
relatively low (Table 4, entry 15-16).
After establishing the one-pot synthetic approach to α,β-
unsaturated oximes, we subsequently focused our attention on
exploring the possibility of preparation of α,β-unsaturated nitriles
from propargylic alcohols by means of introducing a dehydrating
promoter into the current reaction system. Different promoters
were investigated into the formation of 3a from 1a, and the
results are shown in table 3.
Table 4. Transformation of propargylic alcohols to α,β-
unsaturated nitrilesa
Table 3. Screening dehydrating promotersa
Entry
Product
Yieldb (%)
R
CN
R
Entry
Promoter (equiv)
Ac2O (1)
Time (h)
18
Yieldb (%)
1
2
3
4
5
6
7
8
R = H (3a)
79
77
73
70
56
80
77
86
1
2
3
4
5
6
56
21
68
67
79
73
R = o-Me (3b)
R = m-Me (3c)
R = p-Me (3d)
R = p-OMe (3e)
R = p-F (3f)
TFAA (1)
18
TsCl (1)
20
TsCl (1.5)
20
TsCl (2)
20
TsCl (2)/4 A MS
20
R = p-Cl (3g)
aAll reactions were performed with 1a (0.2 mmol), NH2OH HCl (1.2 equiv),
PTSA (0.3 equiv), and promoter in DCE (1 mL) at 90 oC.
bYields are given for isolated products.
CN
Acetic anhydride (Ac2O), a known dehydrating reagent in the
conversion of oxime to nitrile,8c was first examined. Treatment of
1a with Ac2O (1 equiv)/PTSA (0.3 equiv)/NH2OH HCl (1.2
equiv) in DCE at 90 oC for 18 h afforded the desired 3,3-
diphenylacrylonitrile 3a in 56% yield. Interestingly, we also
isolated a heterocyclic compound, 4-phenylquinoline, which is
believed to be generated via the intramolecular electrophilic
substitution of the benzene moiety with O-acetyl-oxime moiety13
(3h)
9
30

4
Tetrahedron
ACCEPTED MANUSCRIPT
N
10c
11c
12c
13c
14c
15c
R = H (3j)
72
76
64
6
Ph
c
R = o-Me (3k)
R = m-Me (3l)
R = p-Me (3m)
R = p-Cl (3n)
NOH
b
O
O
NH2
70
59
32
NH2
NH2
a
d
5
4
2a
NH2
CN
e
16c
22
7
3h
g
8
f
NC
aUnless otherwise noted, all reactions were performed with 1a (0.2 mmol),
NH2OH HCl (1.2 equiv), PTSA (0.3 equiv), and p-TsCl (2 equiv) in DCE (1
mL) at 90 oC for 20 h.
CN
O
S
9
10
bYields are given for isolated products.
Scheme
3
Further application of the products:
LiAlH4/Et2O, r.t., 81%; (b) Cu(OAc)2/Toluene, 80 C, 94%;
(a)
cThe reactions were performed using a modified procedure: 1a (0.2 mmol),
PTSA (0.3 equiv) and DCE (1 mL) were first stirred at 90 oC for 30 min; then
NH2OH HCl (1.2 equiv) and p-TsCl (2 equiv) were added to the reaction
system, and the resulting mixture was stirred at 90 oC for another 20 h.
o
t
(c) i. AcCl/pyridine, r.t.; ii. BuOH, Hg lamp, 50% (two
steps); (d) LiAlH4/AlCl3/Et2O,
0
oC -r.t., 85% (e)
K2CO3/EtOH-H2O (v/v 1:20), MW 150 oC, 92%; (f)
Ac2O/Mg/TMSCl/DMF, r.t., 76%; (g) LiOH/PhSH, r.t., 95%.
Our one-pot approach was proved to be applicable for the
gram-scale preparation of α,β-unsaturated nitriles from
propargylic alcohols. As shown in Scheme 2, 3a could be
synthesized on a scale of more than 3.5 g in one batch without
any decrease in the yield.
The plausible mechanism of the cascade reaction has been
proposed according to the literatures8h,8i,12a,21 (Scheme 4). First,
propargylic alcohol 1 is dehydrated under the catalysis of PTSA
to generate the cation A. Then, either H2O (path a) or
NH2OH HCl (path b) may attack the allenyl cation B, resulting in
the formation of the α,β-unsaturated aldehyde 11’ via the allenic
alcohol C or the α,β-unsaturated oxime 2 via the N-allenic
hydroxylamine D, respectively. In path a, 11’ then reacts with
NH2OH HCl to produce the oxime 2. Finally, when p-TsCl is
employed to the reaction mixture, 2 can be transformed to the
final α,β-unsaturated nitrile 3 through tosylation of the oximido
group in 2, followed by the elimination of PTSA from the
intermediate E.
Scheme 2 Gram-scale preparation of
3a.
α,β-unsaturated nitrile
The application of those prepared α,β-unsaturated oxime and
nitrile, which are versatile building blocks in organic synthesis,
were also carried out (Scheme 3). Oxime 2a was readily
converted into various nitrogen-containing compounds, for
example, amine 4 and amide 5 (Scheme 3, a and b)14,15. Notably,
this kind of β, β-diaryl-α,β-unsaturated oximes could also be used
as the starting materials in the construction of the useful
quinoline skeleton (Scheme 3, c)16. In addition to transformation
to other nitrogen-containing derivatives (e.g. Scheme 3, d and
e)17,18, α,β-unsaturated nitrile 3c could be widely utilized in the
formation of new carbon-carbon or carbon-hetero atom bond
(e.g. Scheme 3, f and g)19,20
.
Scheme 4 Plausible mechanism for the formation of
α,β-
unsaturated oximes and nitriles.
To further investigate the mechanism, a control experiment
was conducted with the standard condition using 1a as the
substrate (seen the supporting information for details). During the
reaction’s proceeding, small portions of the reaction solution
were taken periodically to determine the key intermediates at
1
different time (5 min, 30 min, 4 h, and 20 h). The H NMR
spectra were listed in Figure 1. It can be seen that the
predominant product in 5 min’s sample was aldehyde (90%) and
only a trace of other products was observed. This result proved
that under the standard condition, propargylic alcohol 1a
underwent path a to form α,β-unsaturated aldehyde first (Figure 1,
1a). As the reaction proceeded, some of aldehyde were consumed

5
(30% left), and meanwhile, a large number of oxime 2a (44%)
and nitrile 3a (19%) were generated (Figure 1, 1b). After 4 h, no
aldehyde was left. The amount of 2a decreased slightly (40%)
while that of 3a increased remarkably (48%) (Figure 1, 1c).
When the reaction was prolonged to 20 h, most of oxime 2a was
converted into the final product 3a (76%) (Figure 1, 1d). Based
on the above experiment, we concluded that path a is the most
possible pathway of this one-pot formation of nitrile from
propargylic alcohol.
PTSA (0.06 mmol, 0.3 equiv) and NH2OH HCl (0.24 mmol,
ACCEPTED MANUSCRIPT
1.2 equiv) were successively added to a solution of propargylic
alcohol (0.20 mmol, 1 equiv) in DCE (1 mL). The reaction
mixture was stirred at 90 oC and monitored periodically by TLC.
After completion of the reaction, the mixture was cooled to room
temperature, and sat. aq NaHCO3 (1 mL) and CH2Cl2 (5 mL)
were added. The organic layer was separated and washed
successively with sat. aq NaHCO3 (2 × 1 mL), H2O (1 mL), and
brine (1 mL), then dried (MgSO4) and filtered. The filtrate was
concentrated in vacuo and the resulting residue was purified by
flash column chromatography [silica gel, EtOAc–PE] to give the
α,β-unsaturated oxime. Compound 2a13 is known compounds.
4.2.2 General procedure for the synthesis of compounds 2j–2l
PTSA (0.06 mmol, 0.3 equiv) were added to a solution of
propargylic alcohol (0.20 mmol, 1 equiv) in DCE (1 mL). The
o
reaction mixture was stirred at 90 C until propargylic alcohol
was completely disappeared (about 30 min). Then NH2OH HCl
(0.24 mmol, 1.2 equiv) was added. The resulting mixture
o
continued to be stirred at 90 C and monitored periodically by
TLC. After completion of the reaction, the mixture was cooled to
room temperature, and sat. aq NaHCO3 (1 mL) and CH2Cl2 (5
mL) were added. The organic layer was separated and washed
successively with sat. aq NaHCO3 (2 × 1 mL), H2O (1 mL), and
brine (1 mL), then dried (MgSO4) and filtered. The filtrate was
concentrated in vacuo and the resulting residue was purified by
flash column chromatography [silica gel, EtOAc–PE] to give the
α,β-unsaturated oxime. Compounds 2j, 2l,22 and 2k23 are known
compounds.
Figure 1 The crude 1H-NMR spectra (in DMSO-d6) of the
formation of nitrile 1c from 1a at different time: (1a) 5 min;
(1b) 30 min; (1c) 4 h; (1d) 20 h.
3. Conclusion
4.2.3 3,3-Diphenyl-2-propenal oxime (2a)
In conclusion, we have developed a practical and efficient
PTSA-catalyzed cascade reaction of propargylic alcohols with
NH2OH HCl to afford α,β-unsaturated nitriles or oximes by using
or not using p-TsCl as the dehydrating promoter. Notable
features of this reaction include readily available starting
material, non-toxic and stable nitrogen source, common and
inexpensive catalyst and reagents, convenient operations, good
functional group compatibility, and suitability for large-scale
preparations. The reaction should therefore have widespread
applications in the construction of α,β-unsaturated oximes and
nitriles either as versatile building blocks or as a privileged motif
in useful natural and designed compounds.
(More polar, 36%, E): Yellow solid; mp: 164-165 oC. 1H-NMR
(DMSO-d6, 600MHz) δ 11.41 (s, 1H), 7.50-7.44 (m, 3H), 7.37-
7.36 (m, 3H), 7.29-7.27 (m, 2H), 7.24 (d, J = 9.6 Hz, 1H), 7.20-
7.18 (m, 2H), 6.92 (d, J = 9.6 Hz, 1H). 13C-NMR (DMSO-d6, 150
MHz) δ 147.8, 144.6, 140.6, 137.7, 129.9, 128.8, 128.6, 128.5,
128.4, 127.6, 114.2.
(Less polar, 60%, Z): Yellow solid; mp: 129-131 oC. 1H-NMR
(DMSO-d6, 600 MHz) δ 11.22 (s, 1H), 7.52 (d, J = 10.2 Hz, 1H),
7.49-7.40 (m, 3H), 7.34-7.28 (m, 5H), 7.19-7.18 (m, 2H), 6.83 (d,
J = 10.2 Hz, 1H). 13C-NMR (DMSO-d6, 150 MHz) δ 148.1,
146.5, 140.4, 138.1, 129.7, 128.6, 128.5, 128.3, 128.1, 127.2,
121.1.
4. Experimental section
4.2.4 3,3-Bis(2-methylphenyl)-2-propenal oxime (2b)
o
1
4.1 General
(More polar, 32%): Yellow solid; mp: 142-143 C. H-NMR
(DMSO-d6, 400 MHz) δ 11.37 (s, 1H), 7.31-7.21 (m, 5H), 7.18-
7.15 (m, 1H), 7.11 (d, J = 7.2 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H),
6.93 (d, J = 9.6 Hz, 1H), 6.80 (d, J = 9.6 Hz, 1H), 2.18 (s, 3H),
2.01 (s, 3H). 13C-NMR (DMSO-d6, 100 MHz) δ 147.6, 144.3,
140.8, 138.1, 135.7, 135.1, 131.1, 130.6, 130.5, 129.5, 128.2,
128.0, 125.9, 125.7, 118.6, 20.6, 19.6. IR (KBr, cm-1) γ 3220.4,
1636.0, 1589.8, 1446.7, 898.2, 751.5. ESI-HRMS calcd for
C17H18NO ([M+H]+) 252.1388, found 252.1381.
1H NMR and 13C NMR spectra were recorded in CDCl3 or
DMSO-d6 on a Bruker Avance 400 or 600 instrument. Chemical
shifts (δ) are referenced to internal TMS, DMSO-d6 or CDCl3.
High-resolution mass spectra were recorded on a Bruker ꢀ axis
Impact mass spectrometer. Melting points were determined by
using a Stuart Scientific SMP10 instrument and are uncorrected.
IR spectra were recorded in the ATR mode on a Nicolet 6700
FT-IR Thermo Scientific spectrometer; only the more significant
peaks are reported. All reagents and solvents were obtained
commercially and used as received without further purification.
Reactions were monitored by TLC on glass-backed plates coated
with a 0.2 mm thickness of silica gel 60 F254; chromatograms
were visualized by UV radiation (254 nm) or by staining with
phosphomolybdic acid, 2,4-dinitrophenylhydrazine and KMnO4.
Flash column chromatography was performed on 300–400 mesh
silica gel.
(Less polar, 43%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.21 (s,
1H), 7.41 (d, J = 10.4 Hz, 1H), 7.29-7.11 (m, 7H), 7.03 (d, J =
7.6 Hz, 1H) , 6.43 (d, J = 10.0 Hz, 1H), 2.22 (s, 3H), 2.00 (s,
3H); 13C-NMR (DMSO-d6, 100 MHz) δ 147.7, 146.3, 140.6,
138.5, 135.6, 135.1, 131.0, 130.5, 130.4, 129.3, 128.0, 127.7,
125.8, 125.7, 125.2, 20.6, 19.6. IR (KBr, cm-1) γ 3233.0, 1618.7,
1480.1, 1455.9, 1379.7, 1036.7, 973.2, 764.2, 730.7. ESI-HRMS
calcd for C17H18NO ([M+H]+) 252.1388, found 252.1389.
4.2.1 General procedure for the synthesis of compounds 2a–2i,
2m-2n
4.2.5 3,3-Bis(3-methylphenyl)-2-propenal oxime (2c)

6
Tetrahedron
ACCEPTED MANUSCRIPT
1
1
(More polar, 29%): H-NMR (DMSO-d6, 400 MHz) δ 11.36
(More polar, 30%): H-NMR (DMSO-d6, 400 MHz ) δ 11.26
(s, 1H), 7.36 (t, J = 7.2 Hz, 1H), 7.26-7.23 (m, 2H), 7.20-7.13 (m,
3H), 7.03-6.97 (m, 3H), 6.92 (d, J = 9.6 Hz, 1H), 2.34 (s, 3H),
2.29 (s, 3H). 13C-NMR (DMSO-d6, 100 MHz) δ 148.1, 144.1,
140.7, 137.8, 137.7, 130.2, 129.4, 129.0, 128.4, 128.3, 127.9,
127.0, 125.0, 114.1, 20.94, 20.91. IR (KBr, cm-1) γ 3224.9,
3022.9, 1602.6, 1446.7, 985.9, 880.9, 785.0, 705.3. ESI-HRMS
calcd for C17H18NO ([M+H]+) 252.1388, found 252.1382.
(Less polar, 52%): 1H-NMR (DMSO-d6, 400 MHz ) δ 11.20 (s,
1H), 7.50 (d, J = 10.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.23-7.19
(m, 2H), 7.13-7.11 (m, 2H), 7.03 (d, J = 7.2 Hz, 1H), 6.97-6.95
(m, 2H), 6.77 (d, J = 10.4 Hz, 1H), 2.32 (s, 3H), 2.26 (s, 3H).
13C-NMR (DMSO-d6, 100 MHz) δ 148.2, 146.8, 140.5, 138.2,
137.8, 137.6, 130.1, 129.0, 128.7, 128.40, 128.38, 127.6, 126.8,
124.5, 120.9, 21.00, 20.96. IR (KBr, cm-1) γ 3261.9, 2251.5,
1602.5, 1455.9, 1342.7, 973.2, 788.5, 700.7. ESI-HRMS calcd
for C17H18NO ([M+H]+) 252.1388, found 252.1392.
(s, 1H), 7.04-7.01 (m, 3H), 6.97-6.94 (m, 2H), 6.92-6.87 (m, 2H),
6.79 (d, J = 9.6 Hz, 1H), 2.28 (s, 3H), 2.24 (s, 3H), 2.13 (s, 3H),
1.95 (s, 3H). 13C-NMR (DMSO-d6, 100 MHz) δ 147.8, 144.6,
138.2, 137.3, 137.2, 135.5, 135.4, 134.9, 131.7, 131.1, 130.4,
129.5, 126.5, 126.2, 118.1, 20.7, 20.6, 20.5, 19.5. IR (KBr, cm-1)
γ 3250.4, 2918.9, 1610.6, 1497.5, 1451.3, 1027.5, 906.5, 822.0,
755.0. ESI-HRMS calcd for C19H21NONa ([M+Na]+) 302.1521,
found 302.1520.
(Less polar, 56%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.11 (s,
1H), 7.42 (d, J = 10.0 Hz, 1H), 7.03-6.88 (m, 6H), 6.37 (d, J =
10.0 Hz, 1H), 2.27 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H), 1.94 (s,
3H). 13C-NMR (DMSO-d6, 100 MHz) δ 147.9, 146.5, 130.1,
137.1, 136.8, 135.8, 135.4, 134.9, 131.6, 131.1, 130.3, 129.3,
126.4, 126.2, 124.6, 20.7, 20.6, 20.5, 19.5. IR (KBr, cm-1) γ
3250.4, 2918.9, 1610.6, 1492.9, 1451.3, 1379.7, 1338.1, 1275.8,
1027.5, 981.3, 821.9, 751.5. ESI-HRMS calcd for C19H21NONa
([M+Na]+) 302.1521, found 302.1516.
4.2.6 3,3- Bis(4-methylphenyl)-2-propenal oxime (2d)
4.2.10
oxime (2h)
2-(5H-Dibenzo[a,d][7]annulen-5-ylidene)-2-propenal
1
(More polar, 33%): Yellow solid; mp: 138.3-140.0 oC. H-
NMR (DMSO-d6, 400 MHz) δ 11.34 (s, 1H), 7.26 (d, J = 7.6 Hz,
2H), 7.17-7.15 (m, 5H), 7.06 (d, J = 7.6 Hz, 2H), 6.93 (d, J = 9.6
Hz, 1H), 2.34 (s, 3H), 2.29 (s, 3H). 13C-NMR (DMSO-d6, 100
MHz) δ 147.8, 144.8, 138.4, 138.1, 137.7, 134.9, 129.9, 129.2,
129.1, 127.6, 113.4, 20.9, 20.8. IR (KBr, cm-1) γ 3250.3, 1606.0,
1581.8, 1505.6, 1430.5, 1379.7, 1027.5, 901.6, 822.0, 755.0. ESI-
HRMS calcd for C17H18NO ([M+H]+) 252.1388, found 252.1385.
(Less polar, 47%): Yellow solid; mp: 131.0-132.0 oC. 1H-NMR
( DMSO-d6, 400 MHz ) δ 11.14 (s, 1H), 7.53 (d, J = 10.4 Hz,
1H), 7.25 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.13 (d, J
= 8.4 Hz, 2H), 7.04 (d, J = 7.6 Hz, 2H), 6.74 (d, J = 10.0 Hz,
1H), 2.35 (s, 3H), 2.28 (s, 3H). 13C-NMR (DMSO-d6, 100 MHz)
δ 148.3, 146.5, 137.82, 137.83, 137.4, 135.3, 129.7, 129.1, 127.1,
120.0, 20.8, 20.7. IR (KBr, cm-1) γ 3241.1, 1593.3, 1510.2,
1405.1, 1342.7, 960.5, 818.5, 730.7. ESI-HRMS calcd for
C17H18NO ([M+H]+) 252.1388, found 252.1380.
o
1
(More polar, 32%): Yellow solid; mp: 118-119 C. H-NMR
(DMSO-d6, 400 MHz) δ 11.40 (s, 1H), 7.49-39 (m, 7H), 7.30 (d,
J = 7.6 Hz, 1H), 6.97 (AB system, J = 12.0 Hz, 2H), 6.93 (d, J =
9.6 Hz, 1H ), 6.68 (d, J = 10.0 Hz, 1H). 13C-NMR (DMSO-d6,
100 MHz) δ 147.7, 143.6, 140.3, 134.8, 134.1, 133.4, 131.1,
130.9, 129.4, 129.3, 128.9, 128.6, 128.5, 128.3, 128.0, 127.0,
119.5. IR ( KBr, cm-1 ) γ 3204.2, 2922.4, 2855.4, 1719.2, 1623.3,
1593.3, 1484.8, 1430.5, 1304.6, 1263.1, 1132.6, 1024.0, 898.2,
801.2, 772.3, 738.8. ESI-HRMS calcd for C17H13NONa
([M+Na]+) 270.0895, found 270.0896.
(Less polar, 25%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.25 (s,
1H), 7.55 (d, J = 10.4 Hz, 1H), 7.47-7.37 (m, 7H), 7.29-7.26 (m,
1H), 6.95 (AB system, J = 12.0 Hz, 2H), 6.19 (d, J = 10.4 Hz,
1H). 13C-NMR (DMSO-d6, 100 MHz) δ 146.9, 146.4, 140.6,
135.2, 134.2, 133.4, 131.2, 130.9, 129.3, 129.2, 128.9, 128.6,
128.4, 128.1, 127.8, 127.0, 125.9. IR (KBr, cm-1) γ 3233.0,
1723.8, 1623.3, 1484.8, 1430.5, 1304.6, 1137.2, 1027.5, 901.6,
801.2, 772.3, 734.2. ESI-HRMS calcd for C17H13NONa
([M+Na]+) 270.0895, found 270.0890.
4.2.7 3,3-Bis(4-fluorophenyl)-2-propenal oxime (2e)
(87%, dr = 1:1.89): 1H-NMR (DMSO-d6, 400 MHz) δ 11.48 (s,
0.53H), 11.29 (s, 1H), 7.50 (d, J = 10.4 Hz, 1H), 7.31-7.14 (m,
13H), 6.93 (d, J = 9.6 Hz, 0.51H), 6.80 (d, J = 10.4 Hz, 1H). 13C-
NMR (DMSO-d6, 100 MHz) δ 163.6 (d, JC-F = 148 Hz), 163.3 (d,
JC-F = 108 Hz), 161.0 (d, JC-F = 140 Hz), 160.8 (d, JC-F = 104 Hz),
147.9, 145.6, 144.5, 144.2, 137.1 (d, JC-F = 12 Hz), 136.9 (d, JC-F
= 12 Hz), 134.3 (d, JC-F = 12 Hz), 133.9 (d, JC-F = 12 Hz), 132.1
(d, JC-F = 32 Hz), 131.85 (d, JC-F = 32 Hz), 129.8 (d, JC-F = 36
Hz), 129.3 (d, JC-F = 32 Hz), 121.7, 115.63 (d, J = 164 Hz),
115.60 (d, J = 84 Hz), 115.5, 115.3, 114.8. IR (KBr, cm-1) γ
3241.1, 2855.4, 1597.5, 1510.2, 1346.2, 1229.6, 1158.0, 977.8,
839.3. ESI-HRMS calcd for C15H11NOF2Na ([M+Na]+)
282.0706, found 282.0795.
4.2.11 3-Phenyl-2-butenal oxime (2i)
(More polar, 24%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.19 (s,
1H), 7.61 (d, J = 9.6 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.41-7.34
(m, 3H), 6.98 (d, J = 9.6 Hz, 1H), 2.24 (s, 3H). 13C-NMR
(DMSO-d6, 100 MHz) δ 144.8, 143.1, 142.1, 129.0, 128.8, 126.3,
114.4, 16.3. ESI-HRMS calcd for C10H11NONa ([M+Na]+)
184.0738, found 184.0744.
(Less polar, 15%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.90 (s,
1H), 8.19 (d, J = 10.0 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.39-
7.40 (m, 3H), 6.49 (d, J = 10.0 Hz, 1H), 2.18 (s, 3H). 13C-NMR
(DMSO-d6, 100 MHz) δ 148.0, 141.8, 141.0, 128.9, 128.3, 125.9,
120.8, 16.3. ESI-HRMS calcd for C10H11NONa ([M+Na]+)
184.0738, found 184.0740.
4.2.8 3,3-Bis(4-chlorophenyl)-2-propenal oxime (2f)
(81%, dr = 1:2.27): 1H-NMR (DMSO-d6, 400 MHz) δ 11.54 (s,
0.44H), 11.37 (s, 1H), 7.54-7.48 (m, 4H), 7.43-7.39 (m, 3H),
7.30-7.26 (m, 3H), 7.23-7.20 (m, 3H), 6.94 (d, J = 9.6 Hz,
0.42H), 6.86 (d, J = 10.0 Hz, 1H). 13C-NMR (DMSO-d6, 100
MHz) δ 147.7, 145.1, 144.2, 143.7, 139.1, 138.9, 136.5, 136.1,
133.6, 133.3, 133.1, 133.0, 131.8, 131.6, 129.4, 128.9, 128.8,
128.73, 128.68, 128.6, 122.3, 115.2. IR (KBr, cm-1) γ 3161.4,
2868.1, 1623.3, 1585.2, 1489.4, 1400.5, 1346.2, 1091.0, 1006.7,
944.4, 831.2. ESI-HRMS calcd for C15H11NOCl2Na ([M+Na]+)
314.0115, found 314.0110.
4.2.12 3-Phenyl-2-propenal oxime (2j)
(More polar, 64%): Yellow solid; mp: 135-137 oC. 1H-NMR
(DMSO-d6, 400 MHz) δ 11.29 (s, 1H), 7.56 (d, J = 7.2 Hz, 2H),
7.40-7.35 (m, 5H), 6.95 (d, J = 15.2 Hz, 1H). 13C-NMR (DMSO-
d6, 100 MHz) δ 147.3, 138.0, 136.0, 129.1, 128.9, 127.3, 116.2.
o
(Less polar, 21%): Yellow solid; mp: 69-71 C. 1H-NMR
(DMSO-d6, 400 MHz) δ 11.14 (s, 1H), 7.92 (d, J = 7.6 Hz, 1H),
7.54 (d, J = 7.6 Hz, 2H), 7.38-7.27 (m, 3H), 6.91 (dd, J = 7.6,
4.2.9 3,3-Bis(2,4-dimethylphenyl)-2-propenal oxime (2g)

7
16.0 Hz, 1H), 6.88 (d, J = 16.0 Hz, 1H). 13C-NMR (DMSO-d6,
100 MHz) δ 150.3, 136.7, 136.1, 128.8, 128.5, 126.8, 123.1.
NMR (DMSO-d6, 100 MHz) δ 155.1, 144.5, 141.4, 139.4,
ACCEPTED MANUSCRIPT
129.3, 128.4, 128.32, 128.28, 128.1, 127.6, 120.3, 31.3, 28.9,
21.6, 13.5. IR (KBr, cm-1) γ 3430.5, 2955.9, 2927.0, 2860.0,
1636.0, 1443.2, 1024.0, 990.6, 764.2, 697.2. ESI-HRMS calcd
for C19H21NONa ([M+Na]+) 302.1521, found 302.1517.
4.2.13 3-(4-Methylphenyl)-2-propenal oxime (2k)
1
(More polar, 43%): Yellow solid; mp: 102-104 oC. H-NMR
(DMSO-d6, 400 MHz) δ 11.20 (s, 1H), 7.45 (d, J = 8.0 Hz, 2H),
7.33-7.26 (m, 2H), 7.19 (d, J = 7.6 Hz, 2H), 6.90 (d, J = 15.6 Hz,
1H), 2.30 (s, 3H); 13C-NMR (DMSO-d6, 100 MHz) δ 147.4,
138.8, 137.9, 133.2, 129.5, 127.2, 115.3, 20.9. IR (KBr, cm-1) γ
3182.2, 2847.3, 1631.4, 1602.5, 1446.7, 1379.7, 1309.2, 1137.1,
977.8, 919.0, 801.2. ESI-HRMS calcd for C10H11NONa
([M+Na]+) 184.0738, found 184.0739.
(Less polar, 30%): 1H-NMR (DMSO-d6, 400 MHz) δ 11.08 (s,
1H), 7.89 (d, J = 5.6 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.16 (d, J
= 8.0 Hz, 2H), 6.85 (dd, J = 6.0, 16.0 Hz, 1H), 6.83(d, J = 16.0
Hz, 1H), 2.29 (s, 3H). 13C-NMR (DMSO-d6, 100 MHz) δ 150.4,
138.0, 136.7, 133.4, 129.4, 126.7, 122.1, 20.9.
4.3.1 General procedure for the synthesis of compounds 3a–3i
PTSA (0.06 mmol, 0.3 equiv), NH2OH HCl (0.24 mmol, 1.2
equiv), and p-TsCl (0.40 mmol, 2 equiv) were successively added
to a solution of propargylic alcohol (0.20 mmol, 1 equiv) in DCE
o
(1 mL). The reaction mixture was stirred at 90 C for 20 hrs.
Then it was cooled to room temperature, and sat. aq NaHCO3 (2
mL) and CH2Cl2 (5 mL) were added. The organic layer was
separated and washed successively with sat. aq NaHCO3 (2 × 2
mL), H2O (2 mL), and brine (1 mL), then dried (MgSO4) and
filtered. The filtrate was concentrated in vacuo and the resulting
residue was purified by flash column chromatography [silica gel,
EtOAc–PE] to give the α,β-unsaturated nitrile. Compound 3a,
3d, 3f,12a 3b,24 3c, 3g,25 3e,26 and 3i12c is known compounds.
4.2.14 3-(4-Chlorophenyl)-2-propenal oxime (2l)
o
1
4.3.2 General procedure for the synthesis of compounds 3j–3p
(More polar, 35%): Yellow solid; mp: 138-139 C. H-NMR
(DMSO-d6, 400 MHz) δ 11.33 (s, 1H), 7.59 (d, J = 8.4 Hz, 2H),
7.42 (d, J = 8.0 Hz, 2H), 7.36 (dd, J = 9.2, 16.0 Hz, 1H), 7.30 (d,
J = 9.2 Hz, 1H), 6.94 (d, J = 15.6 Hz, 1H); 13C-NMR (DMSO-d6,
100 MHz) δ 147.0, 136.5, 134.9, 133.4, 128.92, 128.89, 116.9.
PTSA (0.06 mmol, 0.3 equiv) were added to a solution of
propargylic alcohol (0.20 mmol, 1 equiv) in DCE (1 mL). The
reaction mixture was stirred at 90 C until propargylic alcohol
o
was completely disappeared (about 30 min). Then NH2OH HCl
o
1
(0.24 mmol, 1.2 equiv) and p-TsCl (0.40 mmol, 2 equiv) were
(Less polar, 29%): Yellow solid; mp: 116-117 C. H-NMR
(DMSO-d6, 400 MHz) δ 11.20 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H),
7.57 (d, J = 8.4 Hz, 2H) , 7.40 (d, J = 8.4 Hz, 2H), 6.95 (dd, J =
8.8, 16.0 Hz, 1H), 6.78 (d, J = 16.0 Hz, 1H). 13C-NMR (DMSO-
d6, 100 MHz) δ 150.1, 135.2, 135.1, 132.8, 128.8, 128.5, 124.0.
o
added. The resulting mixture continued to be stirred at 90 C for
an 20 hrs. Then it was cooled to room temperature, and sat. aq
NaHCO3 (2 mL) and CH2Cl2 (5 mL) were added. The organic
layer was separated and washed successively with sat. aq
NaHCO3 (2 ×2 mL), H2O (2 mL), and brine (1 mL), then dried
(MgSO4) and filtered. The filtrate was concentrated in vacuo and
the resulting residue was purified by flash column
chromatography [silica gel, EtOAc–PE] to give the α,β-
unsaturated nitrile. Compounds 3j-3o12b are known compounds.
4.2.15 3,3-Diphenyl-O-methyl-2-propenal oxime (2m)
1
(More polar, 38%): Yellow solid; mp: 75-76 oC. H-NMR
(CDCl3, 400 MHz) δ 7.74 (d, J = 10.4 Hz, 1H), 7.40-7.36 (m,
3H), 7.30 (br s, 5H), 7.24-7.22 (m, 2H), 6.77 (d, J = 10.0 Hz,
1H), 3.88 (s, 3H). 13C-NMR (CDCl3, 100 MHz) δ 149.4, 149.2,
140.9, 138.3, 130.2, 128.5, 128.3, 128.1, 127.7, 120.3, 61.8. IR
(KBr, cm-1) γ 3057.5, 2935.1, 2898.2, 2818.5, 1602.6, 1559.8
1489.4, 1446.7, 1363.5, 1174.2, 1049.4, 893.6, 767.7, 734.2,
700.7. ESI-HRMS calcd for C16H15NONa ([M+Na]+) 260.1051,
found 260.1058.
4.3.3 3,3-Diphenyl-2-propenenitrile (3a)
1H-NMR (CDCl3, 400 MHz) δ 7.46-7.42 (m, 6H), 7.39-7.35
(m, 2H), 7.30-7.28 (m, 2H), 5.73 (s, 1H). 13C-NMR (CDCl3, 100
MHz) δ 163.1, 138.8, 137.0, 130.4, 130.0, 129.5, 128.6, 128.5,
128.4, 117.9, 94.8.
(Less polar, 51%): Yellow solid; mp: 53-54 oC. 1H-NMR
(CDCl3, 400 MHz) δ 7.40-7.37 (m, 3H), 7.31-7.30 (m, 5H), 7.24-
7.22 (m, 2H), 7.20 (d, J = 10.0 Hz, 1H), 7.07 (d, J = 10.0 Hz,
1H), 3.95 (s, 3H). 13C-NMR (CDCl3, 100 MHz) δ 150.6, 146.1,
141.0, 138.0, 130.4, 128.8, 128.4, 128.28, 128.26, 114.6, 62.0. IR
(KBr, cm-1) γ 3052.9, 2931.63, 1606.0, 1492.9, 1443.2, 1049.4,
868.1, 772.3, 700.7. ESI-HRMS calcd for C16H15NONa
([M+Na]+) 260.1051, found 260.1053.
4.3.4 3,3-Dis(2-methylphenyl)-2-propenenitrile (3b)
o
1
Yellow solid; mp: 80-81 C. H-NMR (CDCl3, 400 MHz ) δ
7.32-7.21 (m, 5H), 7.20-7.16 (m, 2H), 7.12 (d, J = 7.6 Hz, 1H),
5.64 (s, 1H), 2.17 (s, 3H), 2.13 (s, 3H). 13C-NMR (CDCl3, 100
MHz) δ 164.2, 138.9, 137.5, 136.0, 135.9, 131.4, 131.0, 129.7,
129.6, 129.432, 129.425, 126.1, 125.9, 117.3, 100.2, 20.8, 20.1.
4.3.5 3,3-Dis(3-methylphenyl)-2-propenenitrile (3c)
1H-NMR (CDCl3, 400 MHz) δ 7.33 (t, J = 8.0 Hz, 1H), 7.27-
7.21 (m, 5H), 7.10-7.07 (m, 2H), 5.69 (s, 1H), 2.38 (s, 3H), 2.34
(s, 3H). 13C-NMR (CDCl3, 100 MHz) δ 163.5, 139.0, 138.3,
138.1, 137.1, 131.1, 130.7, 130.0, 128.9, 128.4, 128.3, 126.6,
125.7, 118.0, 94.5, 21.32, 21.30.
4.2.16 1,1-Diphenylhept-1-en-3-one oxime (2n)
1
(More polar, 7%): H-NMR (DMSO-d6, 400 MHz) δ 10.98 (s,
1H), 7.42-7.36 (m, 3H), 7.35-7.26 (m, 3H), 7.21-7.16 (m, 4H),
6.55 (s, 1H), 1.92 (t, J = 7.6 Hz, 2H), 1.23-1.15 (m, 2H), 0.99-
0.89 (m, 2H), 0.69 (t, J = 7.2 Hz, 3H). 13C-NMR ( DMSO-d6, 100
MHz ) δ 157.7, 143.5, 142.2, 139.7, 129.5, 128.3, 128.2, 127.8,
127.6, 127.1, 125.1, 27.6, 25.5, 22.3, 13.5. IR (KBr, cm-1) γ
3405.1, 2955.9, 2922.4, 2855.4, 1644.1, 1492.9, 1446.7, 1024.0,
990.6, 764.2, 697.2. ESI-HRMS calcd for C19H21NONa
([M+Na]+) 302.1521, found 302.1519.
(Less polar,11%): 1H-NMR (DMSO-d6, 400 MHz ) δ 10.78 (s,
1H), 7.41-7.39 (m, 3H), 7.35-7.33 (m, 3H), 7.24-7.22 (m, 2H),
7.13-7.11 (m, 2H), 6.75 (s, 1H), 1.65 (t, J = 7.2 Hz, 2H), 1.24-
1.17 (m, 2H), 1.05-0.95 (m, 2H), 0.67 (t, J = 7.2 Hz, 3H). 13C-
4.3.6 3,3-Dis(4-methylphenyl)-2-propenenitrile (3d)
Yellow solid; mp: 110-113 oC. 1H-NMR (CDCl3, 400 MHz ) δ
7.32 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.20-7.15 (m,
4H), 5.65 (s, 1H), 2.41 (s, 3H), 2.38 (s, 3H), 13C-NMR (CDCl3,
100 MHz) δ 163.1, 140.7, 140.2, 136.3, 134.3, 129.5, 129.3,
129.1, 128.4, 118.3, 93.3, 21.4, 21.3.
4.3.7 3,3-Dis(4-methoxyphenyl)-2-propenenitrile (3e)

8
Tetrahedron
ACCEPTED MANUSCRIPT
o
1
4.3.16 (2E)-3-(4-Chlorophenyl)-2-propenenitrile (3n)
Yellow solid; mp: 105-106 C. H-NMR (CDCl3, 400 MHz )
δ 7.39 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 6.95 (d, J =
8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 5.54 (s, 1H), 3.85 (s, 3H),
3.83 (s, 3H). 13C-NMR (CDCl3, 100 MHz) δ 162.3, 161.4, 160.9,
131.6, 131.2, 130.1, 129.5, 118.7, 113.9, 113.8, 91.5, 55.4, 55.3.
o
1
Yellow solid; mp: 85-86 C. H-NMR (CDCl3, 400 MHz ) δ
7.38 (br s, 4H), 7.35 (d, J = 16.4 Hz, 1H), 5.87 (d, J = 16.8 Hz,
1H). 13C-NMR (CDCl3, 100 MHz) δ 149.0, 137.1, 131.9, 129.3,
128.5, 117.8, 96.9.
4.3.8 3,3-Dis(4-fluorophenyl)-2-propenenitrile (3f)
4.3.17 (2E)-3-(2-Naphthalenyl)-2-propenenitrile (3o)
Yellow solid; mp: 78-80 oC. 1H-NMR (CDCl3, 400 MHz ) δ
7.46-7.41 (m, 2H), 7.31-7.26 (m, 2H), 7.18-7.12 (m, 2H), 7.11-
7.05 (m, 2H), 5.68 (s, 1H). 13C-NMR (CDCl3, 100 MHz) δ 165.1
(d, JC-F = 172 Hz), 162.6 (d, JC-F = 164 Hz), 160.8, 134.9 (d, JC-F
= 12 Hz), 132.8 (d , JC-F = 12 Hz), 131.6 (d, JC-F = 32 Hz), 130.4
o
1
White solid; mp: 131-132 C. H-NMR (CDCl3, 600 MHz ) δ
7.87-7.86 (m, 4H), 7.56-7.53 (m, 4H), 5.98 (d, J = 16.8 Hz, 1H).
13C-NMR (CDCl3, 150 MHz) δ 150.5, 134.5, 133.1, 131.0, 129.6,
129.1, 128.7, 127.8, 127.7, 127.1, 122.2, 118.3, 96.3.
(d, JC-F = 36 Hz), 117.6, 116.0 (d, JC-F = 24 Hz), 115.7 (d, JC-F
24 Hz), 94.8.
=
4.3.18 (2E)-3-(2-Thienyl)-2-propenenitrile (3p)
1H-NMR (CDCl3, 400 MHz) δ 7.50-7.23 (m, 2H), 7.24 (s, 1H),
7.08 (s, 1H), 5.65 (d, J = 16.4 Hz, 1H). 13C-NMR (CDCl3, 100
MHz) δ 142.7, 138.3, 131.2, 129.2, 128.3, 118.0, 94.4.
4.3.9 3,3-Dis(4-chlorophenyl)-2-propenenitrile (3g)
o
1
Yellow solid; mp: 96-97 C. H-NMR (CDCl3, 400 MHz) δ
7.44 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 4H), 7.22 (d, J = 8.4
Hz, 2H), 5.73 (s, 1H). 13C-NMR (CDCl3, 100 MHz) δ 160.6,
136.94, 136.87, 136.5, 134.9, 130.8, 129.6, 129.1, 129.0, 117.3,
95.7.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (21302119, 21471093).
4.3.10 3,3-Dis(2,4-dimethylphenyl)-2-propenenitrile (3h)
White solid; mp: 81-82 oC. 1H-NMR (CDCl3, 400 MHz) δ 7.17
(d, J = 8.0 Hz, 1H), 7.04-6.96 (m, 5H), 5.57 (s, 1H), 2.33 (s, 3H),
2.31 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H). 13C-NMR (CDCl3, 100
MHz) δ 164.3, 139.4, 139.3, 136.3, 135.8, 135.7, 135.0, 132.1,
131.7, 129.64, 129.61, 126.8, 126.6, 117.6, 99.2, 21.2, 21.1, 20.7,
20.0. IR (KBr, cm-1) γ 2922.4, 2214.6, 1610.63, 1589.8, 1497.5,
1446.7, 813.9. ESI-HRMS calcd for C19H19NNa ([M+Na]+)
284.1415; found 284.1416.
References
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4.3.11 3-Phenyl-2-butenenitrile (3i)
1
(E)-3i: H-NMR (CDCl3, 400 MHz) δ 7.47-7.40 (m, 5H), 5.62
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1
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4.3.12 (2E)-3-Phenyl-2-propenenitrile (3j)
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o
1
White solid；mp: 70-71 C. H-NMR (CDCl3, 400 MHz) δ
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