Synthesis of iminonitriles by oxone/tbab-mediated one-pot oxidative three-component strecker reaction

Article abstract of DOI:10.1055/s-0032-1316908

Oxidative three-component reaction of aldehydes, amines, and TMSCN in a biphasic solvent system (toluene/H₂O) containing Oxone, tetra-n-butylammonium bromide (TBAB) and sodium bicarbonate afforded α-iminonitriles in good to excellent yields. This oxidative Strecker reaction was applicable to a wide range of aldehydes and amines, aromatic or aliphatic, of different electronic and steric properties. Substituted 1-aza-2-cyano-1,3-dienes were also accessible using α,β-unsaturated aldehydes as inputs.

Full text of DOI:10.1055/s-0032-1316908

1380▌
PAPER
paper
Synthesis of Iminonitriles by Oxone/TBAB-Mediated One-Pot Oxidative
Three-Component Strecker Reaction
Oxidative Three-Component Strecker Reaction to Iminonitriles
Jean-Baptiste Gualtierotti, Xavier Schumacher, Qian Wang, Jieping Zhu*
Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne,
Switzerland
Fax +41(21)6939740; E-mail: jieping.zhu@epfl.ch
Received: 18.03.2013; Accepted after revision: 20.03.2013
IBX, TBAB
R2NH2
R2
Abstract: Oxidative three-component reaction of aldehydes,
amines, and TMSCN in a biphasic solvent system (toluene/H2O)
containing Oxone, tetra-n-butylammonium bromide (TBAB) and
sodium bicarbonate afforded α-iminonitriles in good to excellent
yields. This oxidative Strecker reaction was applicable to a wide
range of aldehydes and amines, aromatic or aliphatic, of different
electronic and steric properties. Substituted 1-aza-2-cyano-1,3-di-
enes were also accessible using α,β-unsaturated aldehydes as inputs.
(1)
(2)
R2
O
2
N
NH
+
R1
H
R1
CN
R1
CN
1
TMSCN
4
3
Oxone, TBAB
NaHCO3
toluene/H2O = 10:1
Scheme 1 Synthesis of iminonitriles by oxidative three-component
Strecker reaction of aldehydes, amines, and TMSCN
Key words: α-iminonitrile, Oxone, α-aminonitrile, oxidative three-
component Strecker reaction, multicomponent reaction
as a green oxidant as it generates nonpolluting by-prod-
ucts. It is known that Oxone can oxidize both 2-iodoso-
benzoic acid (IBA), a reduced form of IBX, and 2-
iodobenzoic acid to IBX. Taking advantage of this obser-
vation, the groups of Vinod,9 Giannis,10 and Ishihara11
have developed efficient protocols for the oxidation of al-
cohols to carbonyl compounds using a catalytic amount of
either IBX, 2-iodobenzoic acid, or 2-iodobenzenesulfonic
acid in the presence of Oxone. Based on these literature
precedents, we were initially interested in performing the
oxidative three-component Strecker synthesis of α-imino-
nitriles in the presence of a catalytic amount of IBX using
Oxone as a terminal oxidant. To reach this goal, oxidation
of aminonitrile 3a, prepared by classical Strecker reaction
of cinnamaldehyde, phenethylamine, and TMSCN, was
chosen as a model reaction. Taking into account the im-
portance of TBAB in our previous IBX-mediated oxida-
tion process, the first trials were performed with IBX (0.1
equiv), Oxone (1.0 equiv), and TBAB (0.1 equiv) in dif-
ferent biphasic solvent systems [EtOAc/H2O (10:1), wet
MeCN, toluene/H2O (10:1)] at different temperatures.
Complete degradation occurred when the reaction was
performed at 70 °C, the required temperature for oxidiz-
ing IBA to IBX, presumably due to the instability of the
α-iminonitrile under these conditions. Interestingly, when
the reaction was performed in toluene/H2O (10:1) at room
temperature, 4a was isolated in 14% yield, which is slight-
ly higher than the loading of IBX. Since IBX can not be
regenerated under these conditions, we hypothesized that
Oxone might also be able to oxidize α-aminonitriles to α-
iminonitriles.
α-Iminonitriles, also known as imidoyl cyanides, are in-
teresting precursors for many functional groups including
amides, keto acids, cyanoenamides, amidines, and N-ke-
teneimines,1 and are easily elaborated to diverse nitrogen-
containing heterocycles.2 In spite of their great synthetic
potential, their use in organic synthesis is underexploited
mainly due to the limited access to this chemical entity.1–3
Indeed, reported methods are generally multistep process-
es leading to α-iminonitriles in low yields with severe lim-
itation of scope. In 2008, our group reported a one-pot
oxidative three-component Strecker reaction for the syn-
thesis of α-iminonitriles from aldehydes, amines, and tri-
methylsilyl cyanide (TMSCN) using o-iodoxybenzoic
acid (IBX)4 as oxidant assisted by tetra-n-butylammoni-
um bromide (TBAB) (Scheme 1, eq 1).5 Subsequently,
new syntheses of functionalized amides, indolizidines,
and polysubstituted pyrroles were developed using α-imi-
nonitriles as key intermediates.1c,2f In our continued ef-
forts aimed at further developing the promising field of α-
iminonitriles, a new user- and eco-friendly protocol with
an even broader application scope was proved necessary.
We report herein that the same oxidative multicomponent
reaction6,7 can be realized using innocuous Oxone as oxi-
dizing agent in the presence of TBAB and sodium bicar-
bonate in a biphasic solvent system (toluene/H2O) to
afford the desired α-iminonitriles in good to excellent
yields (Scheme 1, eq 2).
Oxone,8 a potassium triple salt (2KHSO5·KHSO4·K2SO4),
is a stable, cheap, and easy-to-handle source of potassium
monopersulfate. It can oxidize a number of functional
groups under mild conditions and is generally considered
Stimulated by this observation, a further survey of reac-
tion conditions was conducted using in situ generated
aminonitrile 3a in aqueous toluene in the absence of IBX.
As shown in Table 1, increasing the quantity of TBAB re-
sulted in a faster reaction and an increase in yield (Table
SYNTHESIS 2013, 45, 1380–1386
Advanced online publication: 08.04.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1316908; Art ID: SS-2013-Z0219-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Oxidative Three-Component Strecker Reaction to Iminonitriles
1381
1, entry 1). It also became apparent that the concentration completion of the Strecker reaction, was also important in
was a vital factor, with the best yield being obtained at order to make a homogeneous solution, a prerequisite for
c = 0.75 M (Table 1, entries 1–3). The stoichiometry and a smooth oxidation reaction. Under these optimum condi-
ratio of Oxone versus TBAB were also important. One tions, iminonitrile 4a was isolated in 92% yield directly
equivalent each of Oxone and TBAB seemed to be opti- from one equivalent each of cinnamaldehyde (1a),
mum (entry 3). When the reaction was carried out in the phenethylamine (2a), and TMSCN. The reaction was per-
presence of 0.5 equivalent of TBAB under otherwise formed on a gram scale without erosion of the product
identical conditions, the yield of 4a went down to 25% yield.
(entries 7 vs 3).
The scope of the reaction was investigated next (Table 2).
The reaction was compatible with a variety of aliphatic,
Table 1 Survey of Reaction Conditions for the Synthesis of Imino-
aromatic, and α,β-unsaturated aldehydes with different
electronic properties, although the electron-rich aromatic
aldehydes gave the corresponding α-iminonitriles with
slightly reduced yield (Table 2, entries 6, 8, 16). The bulk-
iness of the aldehydes has no major impact to the reac-
tion’s outcome as 2,2-dimethylpropanal (entry 5) and 2,6-
dichlorobenzaldehyde (entry 7) were well accepted sub-
strates. Anilines, including highly oxidizable p-methoxy-
aniline, participated efficiently in this reaction (entry 14).
Aliphatic amines including cyclopropylamine were toler-
ated. Interestingly, amino alcohols can be used directly
without the competitive oxidation of the hydroxyl group,
which was in situ protected to the trimethylsilyl ether un-
der the reaction conditions (entry 3). Other common pro-
tective groups such as TBS ether (entry 8) and acetal
(entry 17) withstood these conditions.
nitrilesa
Ph
H2N
O
toluene/H2O
(10:1), r.t.
CN
2a
Ph
+
Ph
H
Ph
N
TMSCN
1a
4a
Entry
Oxone/TBAB NaHCO3 Concn
Time
(h)
Yield
(%)b
(equiv)
(M)
1
2
1:1
–
0.25
0.5
3.5
1
57
65
75
68
61
79
25
29
10
83
88
86
92
1:1
–
3
1:1
–
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75c
0.5
2
4
1:2
–
5
2:1
–
0.3
0.2
2
It is noteworthy that besides aldehydes12 and amines,13
both the double bonds14 and imines15 could potentially be
oxidized by Oxone as an excess amount of oxidant was
present in the reaction mixture. The chemoselectivity ob-
served in this reaction was therefore truly remarkable.
6
2:2
–
7
1:0.5
0.55:1
0.55:0.5
1:1
–
8
–
2
9
–
3
Control experiments indicated that the presence of TBAB
is important to the success of the process. As TBAB could
potentially be oxidized to bromine,16 an additional exper-
iment using bromine as oxidant was performed. However,
only complete degradation was observed. On the other
hand, reaction of α-aminonitrile 3a with preformed tetra-
n-butylammonium–Oxone salt (TBA-Oxone)17 in anhy-
drous toluene gave the desired α-iminonitrile 4a in com-
parable yield to the developed method. Therefore, we
assumed that TBAB served, under our conditions, simply
as a phase-transfer agent. Indeed, reaction of 1a, 2a, and
TMSCN using tetra-n-butylammonium hydrogen sulfate
(TBAHS) instead of TBAB under otherwise identical
conditions afforded the iminonitrile 4a in comparable
yield. The fact that cyclopropylamine participated in the
reaction efficiently (entries 2, 13) allowed us to exclude
the radical mechanism as cyclopropylamine cation radi-
cals are known to undergo fragmentation leading to ring-
opened products.18 Without detailed mechanistic studies,
we propose that the oxidation of α-aminonitriles to α-im-
inonitriles could go through the corresponding hydroxyl-
amine intermediates.19 Subsequent β-elimination of water
would afford the α-iminonitriles.7b
10
11
12
13
1
0.75
0.5
0.7
0.5
1:1
1.5
2
1:1
1:1
1.5
a Reaction conditions: To a solution of aldehyde 1 (0.1 mmol), amine
2 (0.1 mmol) and TMSCN (0.1 mmol) in toluene/H2O (10:1) was add-
ed NaHCO3 (0.15 mmol), Oxone (0.1 mmol), and TBAB (0.1 mmol)
portionwise at r.t.
b Yield of isolated product.
c Reaction carried out at 0 °C.
The acidity of the reaction mixture increased as Oxone
was consumed and reached, at full conversion, around pH
1, which was much higher than that of the IBX protocol
(pH 3). Knowing the acid vulnerability of α-iminonitriles,
the reaction mixture was buffered with NaHCO3. Satisfy-
ingly, yields were indeed increased significantly (entries
10–13). Overall, the optimum conditions found consisted
of performing the reaction in toluene/H2O (1:1, c = 0.75
M) at 0 °C in the presence of Oxone (1.0 equiv), TBAB
(1.0 equiv), and NaHCO3 (1.5 equiv). Note that slow ad-
dition of inorganic salts under vigorous stirring, after the
© Georg Thieme Verlag Stuttgart · New York
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J.-B. Gualtierotti et al.
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Table 2 Synthesis of Iminonitriles by Oxone/TBAB-Mediated One-Pot Three-Component Oxidative Strecker Reactiona
R2
Oxone, TBAB
NaHCO3
O
N
R2NH2
+
TMSCN
+
R1
H
R1
CN
toluene/H2O
(10:1)
1
2
4
Entry
1
R1
Ph
R2
Product
Yield (%)b
CN
CN
CN
NPh
Ph
89
4b
4c
4d
N
2
3
Ph
Ph
87
57
OTMS
N
MeCH(OH)CH2
CN
4
5
n-Bu
t-Bu
Bn
Bn
78
94
n-Bu
NBn
4e
CN
t-Bu
NBn
4f
CN
NCH2CH2Ph
6
7
8
PhCH2CH2
PhCH2CH2
PhCH2CH2
70
84
75
MeO
Cl
MeO
4g
Cl
CN
NCH2CH2Ph
Cl
Cl
4h
CN
MeO
MeO
NCH2CH2Ph
TBSO
TBSO
4i
CN
PhCH2CH2
NCH2CH2Ph
9
PhCH2CH2
MeCH=CH
PhCH2CH2
PhCH2CH2
95
93
4j
CN
NCH2CH2Ph
10
4k
Synthesis 2013, 45, 1380–1386
© Georg Thieme Verlag Stuttgart · New York

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Oxidative Three-Component Strecker Reaction to Iminonitriles
1383
Table 2 Synthesis of Iminonitriles by Oxone/TBAB-Mediated One-Pot Three-Component Oxidative Strecker Reactiona (continued)
R2
Oxone, TBAB
NaHCO3
O
N
R2NH2
+
TMSCN
+
R1
H
R1
CN
toluene/H2O
(10:1)
1
2
4
Entry
11
R1
R2
Product
Yield (%)b
CN
CN
NCH2CH2Ph
MeCH=C(Me)
PhCH2CH2
PhCH2CH2
63
4l
NCH2CH2Ph
12
13
Me2C=CH
76
88
4m
CN
Ph
N
4n
OMe
CN
N
14
4-MeOC6H4
93
O2N
O2N
4o
CN
NCH2CH2Ph
15c
PhCH2CH2
89
77
Br
Br
4p
CN
NBn
16
Bn
MeO
MeO
4q
CN
NCH2CH2Ph
O
O
17c
PhCH2CH2
88
O
O
4r
a Reaction conditions: A solution of aldehyde 1 (0.1 mmol), amine 2 (0.1 mmol), and TMSCN (0.1 mmol) in toluene was stirred until the com-
plete consumption of starting materials. H2O (10% by volume) was added, followed by portionwise NaHCO3 (0.15 mmol), Oxone (0.1 mmol),
and TBAB (0.1 mmol).
b Isolated yield after FCC on silanized silica gel.
c CH2Cl2/H2O (10:1) was used as solvent for better solubility.
In summary, we have described an efficient, practical, and broad application scope and good to excellent yields. This
chemoselective method for the synthesis of α-iminoni- mild and simple protocol provides a valuable alternative
triles by a one-pot oxidative three-component Strecker re- to the existing methodologies and paves the way to further
action. Oxone was used as oxidant in a biphasic solvent exploit the synthetic potential of α-iminonitriles.
system in the presence of TBAB and NaHCO3. Key fea-
tures are: a) operational simplicity without the need of an-
Mass spectra were determined with a Waters ACQUITY H-class
hydrous and inert atmospheric conditions; b) use of
relatively innocuous Oxone as oxidizing agent; c) the for-
mation of harmless potassium salts as by-products; and d)
UPLC/MS ACQ-SQD by electron ionization (EI positive and neg-
ative) or a Finnigan TSQ7000 by electrospray ionization (ESI+).
The accurate masses were done by the mass spectrometry service of
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1380–1386

1384
J.-B. Gualtierotti et al.
PAPER
the EPFL by ESI-TOF using a QTOF Ultima from Waters. NMR
spectra were recorded on a Bruker Avance III-400, Bruker Avance-
1H NMR (400 MHz, CDCl3): δ = 8.02–7.98 (m, 2 H), 7.56–7.42 (m,
3 H), 4.22 (m, 1 H), 3.96 (d, J = 6.0 Hz, 2 H), 1.31 (d, J = 6.0 Hz, 3
H), 0.09 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 142.8, 133.8, 132.4, 129.1, 127.8,
110.1, 68.1, 66.6, 22.4, 0.4.
HRMS (ESI): m/z calcd for C14H21N2OSi+ [M + H]+: 261.1418;
found: 261.1427.
1
400 or Bruker DPX-400 spectrometer at r.t.; H frequency is at
400.13 MHz and 13C frequency is at 100.62 MHz. Chemical shifts
(δ) are reported in parts per million (ppm) from TMS. NMR exper-
iments were carried out in CDCl3. Standard abbreviations were used
1
for denoting the multiplicities in the H NMR spectra. Coupling
constants (J) are reported in hertz (Hz). IR spectra were recorded in
a Jasco FT/IR-4100 spectrometer outfitted with a PIKE technology.
Melting points were determined using a Stuart SMP30 and are un-
corrected. Flash column chromatography (FCC) was performed us-
ing Silicycle silica gel: 230–400 mesh (40–63 μm). Reactions were
monitored using Merck Kieselgel 60 F254 on aluminum sheets.
TLC analyses were visualized by UV fluorescence (254 nm), fol-
lowed by one of the following: KMnO4, ninhydrine, Pancaldi solu-
tion [molybdatophosphorus acid and Ce(IV) sulfate in 4% H2SO4];
p-anisaldehyde, or vanillin. All reagents were obtained from com-
mercial suppliers, unless otherwise stated.
N-Benzylpentanimidoyl Cyanide (4e)
Yield: 15.6 mg (78%); clear oil.
1H NMR (400 MHz, CDCl3): δ = 7.41–7.28 (m, 5 H), 4.93 (s, 2 H),
2.61 (t, J = 7.5 Hz, 2 H), 1.74–1.67 (m, 2 H), 1.44–1.35 (m, 2 H),
0.96 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.0, 137.4, 128.7, 128.0, 127.6,
110.7, 62.3, 38.5, 27.7, 22.0, 13.7.
HRMS (ESI): m/z calcd for C13H17N2+ [M + H]+: 201.1386; found:
201.1381.
Iminonitriles 4; General Procedure
N-Benzylpivalimidoyl Cyanide (4f)
Yield: 18.6 mg (93%); clear oil.
To a solution of aldehyde 1 (0.1 mmol, 1.0 equiv) in toluene (1.3
mL, c = 0.75 M) was added amine 2 (0.1 mmol, 1.0 equiv) at r.t. The
mixture was stirred until the disappearance of the starting materials
(1 min for most aldehydes, up to 4 h for electron-rich aromatic al-
dehydes) before TMSCN (0.1 mmol, 1.0 equiv) was added. The
mixture was stirred for 5 min before the portionwise addition of
H2O (10% by volume), NaHCO3 (0.15 mmol, 1.5 equiv), Oxone
(0.1 mmol, 1.0 equiv), and TBAB (0.1 mmol, 1.0 equiv) at 0 °C.
The biphasic mixture was then stirred vigorously at r.t. until the dis-
appearance of the intermediate; the biphasic mixture was then par-
titioned between sat. aq NaHCO3 (20 mL) and EtOAc (20 mL). The
aqueous phase was extracted with EtOAc (2 ×) and the combined
organic phases were washed with brine, dried (Na2SO4), and con-
centrated in vacuum. The residue was purified by FCC (pentane
then PE–EtOAc, 95:5) to yield the respective pure α-iminonitrile 4.
IR (film): 2969, 1699, 1631, 1456, 1367, 1261, 1161, 1088, 736,
696 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.49–7.20 (m, 5 H), 4.96 (s, 2 H),
1.30 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 152.9, 137.8, 128.6, 127.7, 127.4,
109.7, 61.7, 39.5, 27.0.
HRMS (ESI): m/z calcd for C13H17N2+ [M + H]+: 201.1386; found:
201.1381.
4-Methoxy-N-phenethylbenzimidoyl Cyanide (4g)
Yield: 18.4 mg (70%); white powder; mp 77–78 °C.
1H NMR (400 MHz, CDCl3): δ = 7.92–7.90 (m, 2 H), 7.32–7.23 (m,
5 H), 6.98–6.95 (m, 2 H), 4.18 (t, J = 8.0 Hz, 2 H), 3.87 (s, 3 H),
3.09 (t, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 162.9, 141.4, 139.1, 129.4, 129.2,
128.6, 126.6, 126.5, 114.4, 109.8, 60.1, 55.7, 37.0.
N-Phenethylcinnamimidoyl Cyanide (4a)
Yield: 23.9 mg (92%); yellow crystals; mp 56–58 °C.
1H NMR (400 MHz, CDCl3): δ = 7.56–7.25 (m, 11 H), 6.98 (d, J =
16 Hz, 1 H), 4.17 (t, J = 8.0 Hz, 2 H), 3.09 (t, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 142.8, 142.6, 138.7, 134.5, 130.3,
129.1, 129.0, 128.6, 128.4, 127.8, 126.6, 125.8, 60.3, 36.9.
2,6-Dichloro-N-phenethylbenzimidoyl Cyanide(4h)
Yield: 25.5 mg (84%); clear oil.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.22 (m, 8 H), 4.36 (t, J = 7.2
Hz, 2 H), 3.17 (t, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 138.4, 137.8, 134.4, 132.3, 131.9,
N-Phenylbenzimidoyl Cyanide (4b)
Yield: 20.4 mg (99%); yellow solid, mixture of isomers.
1H NMR (400 MHz, CDCl3): δ = 8.23–8.09 (m, 2 H), 7.65–7.44 (m,
5 H), 7.36–7.04 (m, 3 H).
129.0, 128.8, 128.4, 126.8, 109.1, 60.8, 36.4.
13C NMR (100 MHz, CDCl3): δ = 149.3, 148.1, 140.4, 140.0, 133.8,
133.5, 133.3, 133.0, 132.6, 129.4, 129.3, 129.2, 128.5, 128.4, 127.5,
122.3, 121.1, 120.5, 111.0, 110.8.
4-[(tert-Butyldimethylsilyl)oxy]-3-methoxy-N-phenethylbenz-
imidoyl Cyanide (4i)
Yield: 29.6 mg (75%); clear oil.
IR (film): 2931, 2858, 2337, 2226, 1699, 1594, 1509, 1288, 912,
841 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 2.1 Hz, 1 H), 7.42 (dd,
J = 8.2, 2.1 Hz, 1 H), 7.31–7.19 (m, 5 H), 6.89 (d, J = 8.2 Hz, 1 H),
4.16 (t, J = 7 Hz, 2 H), 3.06 (t, J = 7 Hz, 2 H), 3.85 (s, 3 H), 0.99 (s,
9 H), 0.17 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 151.6, 149.4, 141.6, 139.1, 129.2,
128.6, 127.6, 126.6, 122.2, 120.9, 109.8, 109.7, 60.0, 55.6, 37.0,
25.8, 18.6, –4.4.
N-Cyclopropylbenzimidoyl Cyanide (4c)
Yield: 14.8 mg (87%); clear oil.
IR (film): 3014, 2216, 1575, 1443, 1268, 1181, 1008, 949, 771, 690
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.90 (dd, J = 8.1, 2.0 Hz, 2 H),
7.51–7.41 (m, 3 H), 3.68–3.62 (m, 1 H), 1.32–1.25 (m, 2 H), 1.25–
1.19 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 138.7, 133.7, 131.6, 128.9, 127.0,
110.8, 41.3, 12.1.
HRMS (ESI): m/z calcd for C23H31N2O2Si+ [M + H]+: 395.2149;
found: 395.2156.
HRMS (ESI): m/z calcd for C11H11N2+ [M + H]+: 171.0917; found:
171.0919.
N-Phenethyl-3-phenylpropanimidoyl Cyanide (4j)
N-{2-[(Trimethylsilyl)oxy]propyl}benzimidoyl Cyanide (4d)
Yield: 24.89 mg (95%); light yellow oil.
Yield: 14.8 mg (57%); clear oil.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.17 (m, 10 H), 3.99 (m, 2
H), 2.97–2.93 (m, 4 H), 2.83–2.79 (m, 2 H).
IR (film): 2960, 1605, 1452, 1251, 1096, 1006, 839, 689 cm–1.
Synthesis 2013, 45, 1380–1386
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Oxidative Three-Component Strecker Reaction to Iminonitriles
1385
13C NMR (100 MHz, CDCl3): δ = 143.8, 139.6, 138.7, 129.1, 128.8,
128.6, 128.6, 126.7, 110.4, 60.1, 40.3, 36.6, 31.8.
HRMS (ESI): m/z calcd for C18H17N2O+ [M + H]+: 277.1335; found:
277.1333.
(2E)-N-Phenethylbut-2-enimidoyl Cyanide (4k)
2-[2-(1,3-Dioxolan-2-yl)ethyl]-N-phenethylbenzimidoyl Cya-
nide (4r)
Yield: 18.4 mg (93%); yellow oil.
Yield: 29.4 mg (88%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.22 (m, 5 H), 6.70 (dq, J =
16.1, 6.8 Hz, 1 H), 6.34 (dd, J = 16.1, 1.4 Hz, 1 H), 4.09 (t, J = 7.2
Hz, 2 H), 3.04 (t, J = 7.2 Hz, 2 H), 1.99 (d, J = 6.8 Hz, 3 H).
IR (film): 3027, 2951, 2880, 1604, 1494, 1454, 1250, 1139, 1030,
945, 898, 769, 749, 700 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.66–7.61 (m, 1 H), 7.45–7.20 (m,
8 H), 4.81 (t, J = 4.7 Hz, 1 H), 4.26 (t, J = 7.2 Hz, 2 H), 4.02–3.92
(m, 2 H), 3.91–3.83 (m, 2 H), 3.14 (t, J = 7.3 Hz, 2 H), 2.99 (m, 2
H), 1.96–1.88 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 142.5, 141.7, 139.0, 132.7, 131.5,
131.1, 130.5, 129.1, 128.7, 126.7, 126.6, 110.3, 104.0, 65.1, 60.7,
36.7, 34.9, 28.2.
13C NMR (100 MHz, CDCl3): δ = 142.6, 142.2, 138.8, 129.9, 129.0,
128.6, 126.6, 109.0, 59.8, 36.8, 18.6.
(2E)-2-Methyl-N-phenethylbut-2-enimidoyl Cyanide (4l)
Yield: 13.3 mg (63%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.19 (m, 5 H), 6.65–6.55 (m,
1 H), 4.09 (t, J = 7.4 Hz, 2 H), 3.03 (t, J = 7.4 Hz, 2 H), 2.11 (s, 3
H), 1.94 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 145.2, 139.2, 137.8, 135.2, 129.1,
128.5, 126.5, 109.3, 59.7, 37.0, 14.9, 12.0.
+
HRMS (ESI): m/z calcd for C21H23N2O2 [M + H]+: 335.1754;
found: 335.1760.
3-Methyl-N-phenethylbut-2-enimidoyl Cyanide (4m)
Yield: 16.1 mg (76%); clear oil.
Acknowledgment
We thank EPFL (Switzerland), the Swiss National Science Founda-
tion (SNF), and the Swiss National Centres of Competence in Re-
search (NCCR) for financial support.
IR (film): 2923, 2215, 1643, 1591, 1453, 1269, 1032, 746, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.20 (m, 5 H), 5.99–5.96 (m,
1 H), 4.07 (t, J = 7.3 Hz, 2 H), 3.03 (t, J = 7.3 Hz, 2 H), 2.11 (s, 3
H), 1.94 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 149.7, 140.1, 139.1, 129.1, 128.6,
126.5, 121.7, 111.0, 59.6, 36.9, 28.0, 20.3.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
HRMS (ESI): m/z calcd for C14H17N2+ [M + H]+: 213.1386; found:
213.1389.
References
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3-(4-Bromophenyl)-N-phenethylacrylimidoyl Cyanide (4p)
Yield: 31.2 mg (92%); white crystals; mp 57–61 °C.
1H NMR (400 MHz, CDCl3): δ = 7.55–7.52 (m, 2 H), 7.40–7.36 (m,
2 H), 7.34–7.28 (m, 3 H), 7.26–7.21 (m, 3 H), 6.93 (d, J = 16.4 Hz,
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(2E)-N-Benzyl-3-(4-methoxyphenyl)acrylimidoyl Cyanide (4q)
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IR (film): 2930, 2839, 2363, 1604, 1579, 1513, 1248, 1174, 1031,
824 cm–1.
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3 H), 5.05 (s, 2 H), 3.85 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.6, 143.1, 142.9, 137.8, 129.6,
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