Cascade Process for Direct Transformation of Aldehydes (RCHO) to Nitriles (RCN) Using Inorganic Reagents NH2OH/Na2CO3/SO2F2 in DMSO

Article abstract of DOI:10.1021/acs.joc.8b03164

A simple, mild, and practical process for direct conversion of aldehydes to nitriles was developed feathering a wide substrate scope and great functional group tolerability (52 examples, over 90% yield in most cases) using inorganic reagents (NH₂OH/Na₂CO₃/SO₂F₂) in DMSO. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable nitriles in a pot, atom, and step-economical manner without transition metals. This protocol will serve as a robust tool for the installation of cyano-moieties to complicated molecules.

Full text of DOI:10.1021/acs.joc.8b03164

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Note
A cascade process for direct transforming aldehydes (RCHO) to nitriles
(RCN) using inorganic reagents NH2OH/Na2CO3/SO2F2 in DMSO
Wan-Yin Fang, and Hua-Li Qin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03164 • Publication Date (Web): 14 Mar 2019
Downloaded from http://pubs.acs.org on March 14, 2019
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A cascade process for direct transforming aldehydes (RCHO) to ni-
triles (RCN) using inorganic reagents NH2OH/Na2CO3/SO2F2 in
DMSO
Wan-Yin Fang, Hua-Li Qin*
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State Key Laboratory of Silicate Materials for Architectures; and School of Chemistry, Chemical Engineering and Life Sci-
ence, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, P. R. China
ABSTRACT: A simple, mild and practical process for direct converting aldehydes to nitriles was developed feathering a wide
substrate scope and great functional-groups tolerability (52 examples, over 90% yield in most cases) using inorganic reagents
(NH2OH/Na2CO3/SO2F2) in DMSO. This method allows transformations of readily-available, inexpensive and abundant aldehydes
to highly valuable nitriles in a pot, atom and step-economical (PASE) manner without transition metals. This protocol will serve as
a robust tool for the installation of cyano-moieties to complicated molecules.
The cyano group is a privileged functionality prevalent in nu-
merous naturally occurring products and biologically active
molecules.1 The value of nitrile motifs has been extensionally
serialized for the preparation of natural products, pharmaceuti-
cals, agricultural chemicals, polymers and dyes as well as pre-
cursors for universal carboxylic acids, amines, amides, alco-
hols, ketones, aldehydes and heterocyclic compounds.2 The
Sandmeyer reaction and Rosenmund−von Braun reaction are
the most frequently used conventional strategies for the con-
struction of nitriles.3 On the other hand, the cyanide-halide
exchange reactions for constructions of nitriles from metal
cyanides or metalloid cyanides with organic halides, generally
suffer from the usage of highly toxic reagents (e.g., NaCN,
KCN, Zn(CN)2 or CuCN).4 To accomplish nitriles synthesis
with minimal effects of the above drawbacks, aldehydes have
been employed as starting materials for assembly of nitriles
due to their readily availability, low-cost, and environment-
friendliness,5-8 to generate nitriles via cleavage of coordinated
cyanide anion,5 transoximation,6 or by using N-containing rea-
gents7 as nitrogen source. Besides, metal-catalyzed dehydra-
tion of aldoximes represents an additional option for the con-
struction of nitriles with high efficiency,8 even though most of
them encounter some limitations of high reaction temperature,
and/or tedious operation procedure. Because of the great im-
portance of nitrile moieties and the limitations of the available
synthetic routes, the development of general, efficient, mild
and reliable methods to synthesize nitriles continues to be of
great significance and highly desirable as a challengeable tar-
get. In 2014, a new click chemistry, sulfonyl (VI) fluoride
exchange (SuFEx), was introduced by professor Sharpless
demonstrating that sulfuryl (VI) fluoride functional group
could be utilized in a controllable and targeted manner for
materials, medicinal and biological applications.9 And Sulfuryl
fluoride (SO2F2), an inexpensive (about 1$/kg), relatively inert
gas (stable up to 400 ºC when dry) was one of the key reagents
for SuFEx click chemistry and versatile manipulations.10
One important goal in modern chemistry is to develop pow-
erful, sustainable, and cost-effective methods from readily
available, inexpensive and abundant starting materials in a pot,
atom and step-economical (PASE) manner with the least re-
quirements of isolation or purification of intermediates.11 An-
other target for sustainable chemistry is to use no-toxic inor-
ganic starting materials to achieve organic synthesis because
the use of inorganic reagents has significant advantages over
their organic counterparts, such as producing the lowest total
organic carbon (TOC) in the waste, easy work-up and purifica-
tion.12
Scheme 1. A proposed cascade process for direct convert-
ing aldehydes to nitriles.
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Viewing on the high value of nitrile moieties, the easy
2af), regardless the substrates functionalized with prevalent
availability of aldehydes, and the advantages of inorganic rea-
gent such as inorganic base (K2CO3 or Na2CO3), NH2OH and
SO2F2 for organic synthesis, and our continuous efforts on
utilization of SO2F2 for chemical transformations,10f-i we pro-
posed a one-pot process for direct converting aldehydes to
nitriles (Scheme 1) through a cascade sequence following a
similar mechanism for the alkyne synthesis.10i We envisioned
(Scheme 1, b) that in polar solvent DMSO, aldehydes 1 would
react with NH2OH under the promotion of inorganic base
(K2CO3) to provide aldoxime intermediates A after dehydra-
tion, subsequently the aldoxime will further react with SO2F2
to generate the corresponding sulfonyl ester B, with the assis-
tant of the same base, the following beta-elimination of pre-
cursor sulfonyl ester B would generate the desired carbon-
nitrogen triple bonds of nitrile 2.
electron-donating or electron-withdrawing groups of ether,
phenyl, halogen, ester, amide, sulfonamide, nitro, and cyano
on the aryl rings. Notably, the position of substituents on the
aryl rings exhibited some influence on the efficiency. The
ortho-position substituted aldehydes possessing steric hin-
drance accomplished the desired transformation in slightly
lower yields than the para-position functionalized substrates
(e.g. 2f compared to 2r). 2s, 2t and 2v were obtained in less
than 90% yield attributing to the steric hindrance of ortho-
substitutions as well. It has to be pointed out that because of
their low boiling-points, the isolated yields of the high-volatile
arylnitriles (2d, 2m, 2v, 2ag and 2ah) were lower than their
HPLC yields. Delightingly, the synthesis of 4-cyanobenzoic
acid (2l) containing a base-sensitive functionality (carboxylic
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acid) was also achieved in good yield (70%) when aldoxime
intermediate was used as starting material for the SO2F2 medi-
After screening a large variety of conditions (see supporting
information for details), we were pleased to find that the pro-
posed transformation (aldehydes to nitriles) was accomplished
when Na2CO3 was used as base in DMSO under SO2F2 atmos-
phere (balloon) in up to nearly quantitative yields.
ated dehydration process using 6.0 equivalent of Na2CO3 even
though the one-pot transformation of para-carboxylic benzal-
dehyde (1l) to the corresponding nitrile was not successful
because the formation of aldoxime intermediate was not
achieved under the developed condition. However, the devel-
oped system was not amenable to the preparation of aromatic
nitriles functionalized with silyl ether moiety on the benzene
ring which may be attributed to the high activity of silyl ether
to react with fluoride anion to form the strong connection of
Si-F bond. Excitingly, the double bond, triple bond and halides
moieties, which are fragile in a lot of previous procedures for
nitriles synthesis, remained intact during this transformation to
provide the corresponding products in nearly quantitative
yields (2d, 2e, 2f, 2q, 2r, 2u, 2w, 2x, 2y, and 2ac). The natu-
rally occurring molecular 6-Bromoveratraldehyde (1y) was
smoothly transformed to the desired nitrile 2y in 96% yield.
Not surprisingly, the precursor for making Roflumilast 1z was
also converted to the corresponding nitrile derivate 2z in quan-
titative yield using this expedient method. It is worth noting,
polycyclic substrates (1aa-1ac) tolerated the cyanation system
well and gave the final products in quantitative yields. Notably,
molecules bearing two aldehyde groups on a single aryl ring or
two different aryl rings were also successfully converted to
their corresponding nitriles in nearly quantitative yields (2ad-
2af). A grams-scale reaction was operated using 1k as model
substrate, and the desired product 2k was generated in 99%
yield, indicating the high possibility of application this method
in big scale production of nitriles.
Table 1. Substrates Scope Examination Using (Hetero)aryl
Aldehydes
Giving the prevalence and wide utilization of heterocyclic
molecular in industrial production and academic research, we
turned our attention to transforming heterocyclic aldehydes to
the corresponding nitriles. Not surprisingly, a broad of hetero-
cyclic aldehydes bearing sulfur, nitrogen and oxygen atoms in
aryl rings (2ag-2an) were smoothly converted to their nitriles
in excellent to quantitative yields. It is worth noting, the alde-
hydes with nitrogen-containing aromatic rings suffering from
low reactivity due to their electronically deficient property and
strong Lewis basicity which were not compatible in many
previous metal catalyzed nitriles synthesis, also provided their
nitriles in quantitative yields (2ai, 2aj, 2ak, 2am and 2an)
using this procedure.
aGeneral condition: aldehydes (1, 2.0 mmol), H2NOH.HCl
(153 mg, 2.2 mmol), Na2CO3 (117 mg, 1.1 mmol) and DMSO
(10 mL), r.t., 30-60 min; then Na2CO3 (1.06 g, 10 mmol) and
SO2F2
gas
(Toxic
by
inhalation.
Operated
in fume hoods), r.t., 12 h. bIsolated yields. cHPLC yields. dAld-
oxime as starting material, Na2CO3 (1.27 g, 12 mmol) was
used. eH2NOH.HCl (307 mg, 4.4 mmol), Na2CO3 (235 mg, 2.2
mmol), DMSO (10 mL); then Na2CO3 (2.12 g, 20 mmol).
fH2NOH.HCl (208 mg, 3.0 mmol) and Na2CO3 (159 mg, 1.5
mmol) was used.
We subsequently evaluated the substrate scopes, functional
group compatibility and limitation of the one-pot process as
illustrated in Table 1. A large set of structurally and electroni-
cally diverse arylaldehydes were examined under the standard
conditions and in most case, the corresponding nitriles were
successfully furnished in excellent to quantitative yields (2a-
To further examine the scope of this method, we expended
this protocol to aliphatic allylic aldehydes (Table 2, 3a-3e).
Excitingly, the allylic aldehydes (3a-3e) were smoothly con-
verted to the corresponding nitriles (4a-4e) in good to excel-
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lent yields with complete retention of original E-configuration
carbaldehyde (10) bearing both alkyl and aryl aldehyde func-
tionalities as the substrate under the optimized conditions
(Scheme 3). The results indicated that the reactivity of alkyl
aldehyde was superior to aryl aldehyde to provide their corre-
sponding nitrile counterparts in about 4:1 ratio generating cya-
nated products 11 and 12 in 68% and 17% yields respectively
without formation of product 13.
of the double bonds (4b, 4c, 4d and 4e). Notably, by elevating
o
the temperature to 50 C, the conversion of regular aliphatic
aldehydes (Table 2, 3f, 3g and 3i) to the desire nitriles (4f, 4g
and 4i) were accomplished in excellent yields. The propargylic
aldehyde 3j was transformed to nitrile 4j in 84% yield at room
temperature as well.
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Table 2. Scope of Converting Allylic, Aliphatic, and Pro-
pargylic Aldehydes to Nitriles
aThe reactions were performed according to conditions in Ta-
ble 1. bIsolated yields. cH2NOH.HCl (208 mg, 3.0 mmol),
Na2CO3 (159 mg, 1.5 mmol) were used. d r.t., 12 h, then 50 oC,
5 h. e r.t., 12 h, then 50 oC, 3 h. fHPLC yield.
Figure 1. Control experiments for mechanism investigation
As illustrated in Figure 1, some control experiments were
conducted to gain insight to the mechanism of this aldehydes
cyanation process. Quantitative yield of 2a was achieved when
the pure aldoxime I was served as starting material (Figure 1b)
which was identically effective as the use of freshly in situ
generated crude aldoxime I from the reaction of aldehyde with
NH2OH (Figure 1f). In addition, mixing the crude aldoxime I
just with Na2CO3 without the presence of SO2F2, the desired
nitrile was not generated (Figure 1c); mixing the crude aldox-
ime I just with SO2F2 without the additional 5.0 equivalent of
Na2CO3, only a trace amount of nitrile was observed (Figure
1d); pre-mixing the crude aldoxime I with SO2F2, then remov-
ing SO2F2 and adding additional 5.0 equivalent of Na2CO3, the
nitrile was formed in negligible yield (Figure 1e); which indi-
cating the generation and elimination of sulfonyl ester were
crucial for this cyanation process.
Scheme 2. Application to Formal Synthesis Tarceva and
Tazanolast
In order to demonstrate the applicability of this novel cya-
nation protocol in synthesis complicated molecules, aldehyde
7 (derived from commercially available aldehyde 5), was sub-
jected to the standard reaction condition and provided the cor-
responding nitrile product 8, a key precursor for Tarceva, in 97%
yield (Scheme 2a).13 In addition, starting from aldehyde 1o,
the formal synthesis tetrazole 9 for asthma medicine Taza-
nolast,14 was achieved in two steps with nearly quantitative
yield by using this newly developed method (Scheme 2b).
Scheme 4. A plausible mechanism for converting aldehydes
to carbon-nitrogen triple bonds
Based on the results of the control experiments, a plausible
mechanism for this cyanation process was proposed in the
Scheme 4. Firstly, aldehydes 1 reacted with H2NOH in the
polar solvent (DMSO) to generate aldoxime intermediate A
through a nucleophilic addition and dehydration process. Then
the corresponding sulfonyl ester B was formed from the reac-
tion of aldoxime intermediate A with SO2F2 under the promo-
tion of Na2CO3. Finally, the sulfonyl ester B underwent a base-
promoted beta-elimination to generate the desired nitrile 2.
Scheme 3. The intramolecular competition reaction be-
tween alkyl and aryl aldehyde moieties
In summary, we have developed a novel, mild, practical and
robust method for the direct converting aldehydes into nitriles
mediated by inorganic system of NH2OH/SO2F2/Na2CO3 in a
pot, atom and step-economical (PASE) manner. Moreover, the
one-pot process was found to be applicable to the synthesis of
key precursors for drugs Tarceva and Tazanolast in nearly
To compare the reactivity between alkyl and aryl aldehyde
moieties during the formation of nitriles through using this
developed reaction system, an intramolecular competition
reaction was conducted with 4'-(4-oxobutyl)-[1,1'-biphenyl]-4-
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quantitative yields. In addition, more than fifty structurally
HRMS calculated for C14H12NO [M+H]+ 210.0913, found:
diverse nitriles were synthesized with greater than 90% yields
in most cases demonstrating the high efficiency, wide scope
and functional-group compatibility of this new protocol.
210.0916.
4-Methoxybenzonitrile (2b).7f Following the Procedure A.
o
White solid, 243 mg, 1.82 mmol, 91% yield. M.p. 54-56 C.
Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
1
column chromatography. H NMR (500 MHz, CDCl3) δ 7.57
EXPERIMENTAL SECTION
GENERAL INFORMATION
(d, J = 8.7 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 3.85 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 162.9, 134.1, 119.3, 114.8,
104.0, 55.6.
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[1,1'-Biphenyl]-4-carbonitrile (2c).7f Following the Proce-
dure A. White solid, 355 mg, 1.98 mmol, 99% yield. M.p. 83-
85 oC. Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent
All reactions were carried out under an air atmosphere. Un-
less otherwise specified, NMR spectra were recorded in CDCl3
or DMSO-d6 on a 500 or 400 MHz (for H), 471 MHz (for
1
19F{1H, 13C}), 126 MHz (for 13C{1H}) spectrometer. All chem-
ical shifts were reported in ppm relative to TMS (1H NMR, 0
ppm) as internal standards. The HPLC experiments were car-
ried out on a Waters e2695 instrument (column: J&K, RP-C18,
5 μm, 4.6 × 150 mm), and the yields of the products were de-
termined by using the corresponding pure compounds as the
external standards. The coupling constants were reported in
Hertz (Hz). The following abbreviations were used to explain
the multiplicities: s = singlet, d = doublet, t = triplet, q = quar-
tet, m = multiplet, br = broad. Melting points were measured
and uncorrected. MS experiments were performed on a TOF-
Q ESI or CI/EI instrument. All reagents used in the reactions
were all purchased from commercial sources and used without
further purification.
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
7.73 (d, J = 7.7 Hz, 2H), 7.69 (d, J = 7.3 Hz, 2H), 7.60 (d, J =
7.4 Hz, 2H), 7.50 (t, J = 7.5 Hz, 2H), 7.44 (t, J = 7.5 Hz, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 145.8, 139.3, 132.7, 129.2,
128.8, 127.8, 127.3, 119.0, 111.0.
4-Fluorobenzonitrile (2d).6 Following the Procedure A. Col-
orless oil, 184 mg, 1.52 mmol, 76% yield. Petroleum ether /
ethyl acetate = 10 : 1 (v / v) as eluent for column chromatog-
1
raphy. H NMR (500 MHz, CDCl3) δ 7.69-7.67 (m, 2H), 7.17
(t, J = 8.3 Hz, 2H). 19F{1H, 13C} NMR (471 MHz, CDCl3) δ -
102.4 (s, 1F). 13C{1H} NMR (126 MHz, CDCl3) δ 165.2 (d, J
= 256.1 Hz), 134.8 (d, J = 9.1 Hz), 118.1, 117.0 (d, J = 22.7
Hz), 108.7 (d, J = 3.6 Hz).
4-Chlorobenzonitrile (2e).7f Following the Procedure A.
General procedures for the cyanation of Aldehydes to Ni-
triles. Procedure A: Aldehyde (2.0 mmol, 1.0 eq.),
H2NOH.HCl (153 mg, 2.2 mmol, or 208 mg, 3.0 mmol),
Na2CO3 (117 mg, 1.1 mmol, or 159 mg, 1.5 mmol) and
DMSO (10 mL, 0.2 M) were added into an oven-dried reaction
tube (30 mL) equipped with a stirring bar, and the reaction
mixture reacted at room temperature for 30-60 min. The reac-
tion was monitored by TLC. After the aldehyde was complete-
ly consumed, another portion of the Na2CO3 (1.06 g, 10 mmol)
was added and the reaction tube was covered with a plastic
stopper before the SO2F2 gas was introduced into the stirring
reaction mixture by slow bubbling through a SO2F2 balloon at
the room temperature for an additional 12 h. After that, the
reaction diluted with water and extracted with dichloro-
methane (3× 20 mL). Then the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and concen-
trated to dryness. The residue was purified through silica gel
chromatography using a mixture of ethyl acetate and petrole-
um ether as eluent to afford the desired nitriles.
o
White solid, 267 mg, 1.94 mmol, 97% yi eld. M.p. 87-89 C.
Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
1
column chromatography. H NMR (500 MHz, CDCl3) δ 7.60
(d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H). 13C{1H} NMR
(126 MHz, CDCl3) δ 139.7, 133.5, 129.8, 118.1, 110.9.
4-Bromobenzonitrile (2f).6 Following the Procedure A.
White solid, 360 mg, 1.98 mmol, 99% yield. M.p. 108-110 oC.
Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 7.63 (d,
J = 8.1 Hz, 2H), 7.52 (d, J = 8.0 Hz, 2H). 13C{1H} NMR (126
MHz, CDCl3) δ 133.5, 132.8, 128.1, 118.2, 111.4.
Methyl 4-cyanobenzoate (2g).7f Following the Procedure A.
o
White solid, 316 mg, 1.96 mmol, 98% yield. M.p. 63-65 C.
Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 8.13 (d,
J = 8.1 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 3.96 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3) δ 165.5, 134.0, 132.3, 130.2, 118.1,
116.5, 52.8.
4-(Methylsulfo nyl)benzonitrile (2h).15 Following the Proce-
Procedure B: After reacting at room temperature for 12 h,
o
dure A. White powder, 369 mg, 1.98 mmol, 99% yield. M.p.
then the reaction mixture was continued to stir at 50 C for
o
142-143 C. Petroleum ether / ethyl acetate = 2 : 1 (v / v) as
further 3 h or 5 h. The reaction was also monitored by TLC.
After completion, the reaction diluted with water and extracted
with dichloromethane (3× 20 mL). Then the combined organic
layers were washed with brine, dried over anhydrous Na2SO4,
and concentrated to dryness. The residue was purified through
silica gel chromatography using a mixture of ethyl acetate and
petroleum ether as eluent to afford the desired nitriles.
eluent for column chromatography. 1H NMR (500 MHz,
DMSO-d6) δ 8.15 (d, J = 8.0 Hz, 2H), 8.12 (d, J = 8.0 Hz, 2H),
3.32 (s, 3H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 144.7,
133.5, 127.8, 117.6, 116.1, 42.9.
4'-Cyano-[1,1'-biphenyl]-4-yl dimethylcarbamate (2i). Fol-
lowing the Procedure A. White solid, 530 mg, 1.98 mmol, 99%
yield. M.p. 147-149 oC. Petroleum ether / ethyl acetate = 3 : 1
4-(Benzyloxy)benzonitrile (2a).7f Following the Procedure A.
1
o
(v / v) as eluent for column chromatography. H NMR (500
White solid, 400 mg, 1.92 mmol, 96% yield. M.p. 91-93 C.
MHz, DMSO-d6) δ 7.91 (d, J = 8.1 Hz, 2H), 7.87 (d, J = 8.2
Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H),
3.06 (s, 3H), 2.93 (s, 3H). 13C{1H} NMR (126 MHz, DMSO-
d6) δ 153.8, 151.9, 143.9, 135.1, 132.9, 128.0, 127.5, 122.6,
118.9, 109.9, 36.3, 36.1. ESI-MS HRMS calculated for
C16H15N2O2 [M+H]+ 267.1128, found: 267.1125.
Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
1
column chromatography. H NMR (500 MHz, DMSO-d6) δ
7.77 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 7.3 Hz, 2H), 7.40 (t, J =
7.1 Hz, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.18 (d, J = 8.9 Hz, 2H),
5.20 (s, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 162.1, 135.8,
134.1, 128.9, 128.5, 127.6, 119.3, 115.7, 104.3, 70.4. ESI-MS
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N-(4-cyanophenyl)acetamide (2j).16 Following the Procedure
1H), 7.76 (t, J = 8.1 Hz, 1H). 13C{1H} NMR (126 MHz,
CDCl3) δ 148.3, 137.7, 130.8, 127.7, 127.3, 116.6, 114.2.
A. White solid, 314 mg, 1.96 mmol, 98% yield. M.p. 201-203
oC. Petroleum ether / ethyl acetate = 1 : 1 (v / v) as eluent for
3-Bromobenzonitrile (2q).20 Following the Procedure A.
1
o
column chromatography. H NMR (500 MHz, DMSO-d6) δ
White solid, 335 mg, 1.84 mmol, 92% yield. M.p. 35-37 C.
10.35 (s, 1H), 7.76-7.73 (m, 4H), 2.09 (s, 3H). 13C{1H} NMR
(126 MHz, DMSO-d6) δ 169.2, 143.5, 133.3, 119.1, 116.9,
104.7, 24.2.
Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 7.78 (s,
1H), 7.74 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.36 (t,
J = 8.0 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 136.2,
134.8, 130.8, 130.7, 123.0, 117.4, 114.3.
4-Nitrobenzonitrile (2k).6 Following the Procedure A. White
solid, 293 mg, 1.98 mmol, 99% yield. M.p. 145-147 oC. Petro-
leum ether / ethyl acetate = 5 : 1 (v / v) as eluent for column
10
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12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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34
35
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37
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46
47
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2-Bromobenzonitrile (2r).20 Following the Procedure A.
1
o
chromatography. H NMR (500 MHz, DMSO-d6) δ 8.38 (d, J
White solid, 331 mg, 1.82 mmol, 91% yield. M.p. 50-51 C.
= 8.7 Hz, 2H), 8.18 (d, J = 8.9 Hz, 2H). 13C{1H} NMR (126
MHz, DMSO-d6) δ 149.9, 134.1, 124.3, 117.3, 117.2.
Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 7.69 (d,
4-Cyanobenzoic acid (2l).10f Aldoxime intermediate of 4-
formylbenzoic acid 1l was synthesized according to a known
procedure:17 4-formylbenzoic acid (1l, 751 mg, 5.0 mmol),
hydroxylamine hydrochloride (695 mg, 2.0 eq.), sodium ace-
tate (2.05 g, 5.0 eq.) and THF (20 mL) was added to a 50 mL
round reaction flask, and the reaction mixture was stirred at a
reflux temperature for 1 h, then washed with water, extracted
with EtOAc (310 mL). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and concen-
trated to dryness to get its aldoxime intermediate as a white
solid (727 mg, 88% yield).
J = 7.8 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.48-7.41 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3) δ 134.4, 134.0, 133.3, 127.8,
125.4, 117.3, 116.0.
2-(Trifluoromethyl)benzonitrile (2s).21 Following the Proce-
dure A. Light yellow oil, 301 mg, 1.76 mmol, 88% yield. Pe-
troleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 7.85 (d,
J = 7.5 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.76 (t, J = 7.5 Hz,
1H), 7.70 (t, J = 7.5 Hz, 1H). 19F{1H, 13C} NMR (471 MHz,
CDCl3) -62.0 (s, 3F). 13C{1H} NMR (126 MHz, CDCl3) δ
134.8, 133.1, 132.8, 132.4, 126.8 (q, J = 4.5 Hz), 122.5 (q, J =
274 Hz), 115.6, 110.3.
Then the synthesis of 4-Cyanobenzoic acid (2l) followed a
modified Procedure. The reaction was performed directly from
the aldoxime intermediate in 2.0 mmol scale and Na2CO3
(1.27 g, 12 mmol) was used for the dehydration process under
SO2F2 atmosphere at r.t. for 12 h. After completion of the reac-
tion, the mixture was acidified with 1M HCl to adjust the pH
value to 1.0. White solid, 206 mg, 1.40 mmol, 70% yield. M.p.
5-Bromo-2-fluorobenzonitrile (2t).22 Following the Proce-
dure A. White solid, 337 mg, 1.68 mmol, 84% yield. M.p. 75-
o
77 C. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
7.76-7.71 (m, 2H), 7.14 (t, J = 8.5 Hz, 1H). 19F{1H, 13C} NMR
(471 MHz, CDCl3) -108.2 (s, 1F). 13C{1H} NMR (126 MHz,
CDCl3) δ 162.4 (d, J = 260.7 Hz), 138.2 (d, J = 8.2 Hz), 135.9,
118.4 (d, J = 20.8 Hz), 117.2 (d, J = 4.5 Hz), 112.6, 103.6 (d, J
= 17.3 Hz).
o
221-222 C. Petroleum ether / ethyl acetate = 1 : 1 (v / v) as
eluent for column chromatography. 1H NMR (400 MHz,
DMSO-d6) δ 13.57 (br s, 1H), 8.07 (d, J = 8.3 Hz, 2H), 7.97 (d,
J = 8.3 Hz, 2H). 13C{1H} NMR (126 MHz, CDCl3) δ 166.9,
135.0, 132.1, 130.3, 118.2, 116.0.
3,4-Dichlorobenzonitrile (2u).19 Following the Procedure A.
o
White solid, 337 mg, 1.96 mmol, 98% yield. M.p. 67-69 C.
Benzonitrile (2m).7f Following the Procedure A. Colorless oil,
132 mg, 1.28 mmol, 64% yield. Petroleum ether / ethyl acetate
= 10 : 1 (v / v) as eluent for column chromatography. 1H NMR
(500 MHz, CDCl3) δ 7.62-7.57 (m, 3H), 7.44 (t, J = 7.5 Hz,
2H). 13C{1H} NMR (126 MHz, CDCl3) δ 132.8, 132.0, 129.1,
118.8, 112.3.
Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
1
column chromatography. H NMR (500 MHz, CDCl3) δ 7.76
(s, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 138.4, 134.2, 133.9, 131.6,
131.2, 116.9, 112.1.
2,6-Dimethylbenzonitrile (2v).23 Following the Procedure A.
Colorless oil, 147 mg, 1.12 mmol, 56% yield. Petroleum ether
/ ethyl acetate = 10 : 1 (v / v) as eluent for column chromatog-
raphy. 1H NMR (500 MHz, CDCl3) δ 7.34 (t, J = 7.6 Hz, 1H),
7.11 (d, J = 7.6 Hz, 2H), 2.52 (s, 6H). 13C{1H} NMR (126
MHz, CDCl3) δ 142.2, 132.2, 127.4, 117.4, 113.4, 20.8.
3-Phenoxybenzonitrile (2n).7f Following the Procedure A.
Colorless oil, 371 mg, 1.90 mmol, 95% yield. Petroleum ether
/ ethyl acetate = 10 : 1 (v / v) as eluent for column chromatog-
1
raphy. H NMR (500 MHz, CDCl3) δ 7.43-7.38 (m, 3H), 7.35
(d, J = 7.6 Hz, 1H), 7.24-7.19 (m, 3H), 7.04 (d, J = 8.4 Hz,
2H). 13C{1H} NMR (126 MHz, CDCl3) δ 158.2, 155.6, 130.7,
130.2, 126.4, 124.7, 122.8, 121.1, 119.8, 118.3, 113.5.
Methyl (E)-3-(3-cyanophenyl)acrylate (2w).24 Following the
Procedure A. White solid, 363 mg, 1.94 mmol, 97% yield.
M.p. 93-94 oC. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as
eluent for column chromatography. 1H NMR (500 MHz,
CDCl3) δ 7.78 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.66-7.63 (m,
2H), 7.51 (t, J = 7.8 Hz, 1H), 6.48 (d, J = 16.0 Hz, 1H), 3.82 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 166.7, 142.2, 135.8,
133.3, 132.0, 131.4, 129.9, 120.7, 118.2, 113.5, 52.1.
Isophthalonitrile (2o).18 Following the Procedure A. White
solid, 251 mg, 1.96 mmol, 98% yield. M.p. 156-157 oC. Petro-
leum ether / ethyl acetate = 3 : 1 (v / v) as eluent for column
1
chromatography. H NMR (500 MHz, CDCl3) δ 7.96 (s, 1H),
7.91 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 2H), 7.66 (t, J = 8.0 Hz, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 136.1, 135.5, 130.5, 116.7,
114.2.
3-(Phenylethynyl)benzonitrile (2x).25 Following the Proce-
3-Nitrobenzonitrile (2p).19 Following the Procedure A. White
solid, 284 mg, 1.92 mmol, 96% yield. M.p. 111-113 oC. Petro-
leum ether / ethyl acetate = 10 : 1 (v / v) as eluent for column
dure A. Light yellow solid, 400 mg, 1.96 mmol, 98% yield.
o
M.p. 67-69 C. Petroleum ether / ethyl acetate = 10 : 1 (v / v)
1
1
as eluent for column chromatography. H NMR (500 MHz,
chromatography. H NMR (500 MHz, CDCl3) δ 8.53 (s, 1H),
CDCl3) δ 7.81 (s, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.60 (d, J =
8.48 (dd, J1 = 8.3 Hz, J2 = 1.0 Hz, 1H), 8.01 (d, J = 8.0 Hz,
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7.8 Hz, 1H), 7.56-7.55 (m, 2H), 7.46 (t, J = 7.8 Hz, 1H), 7.39-
3-(4-Cyanophenoxy)benzonitrile (2af).28 Following the Pro-
7.38 (m, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 135.7,
135.0, 131.9, 131.5, 129.4, 129.1, 128.6, 125.1, 122.4, 118.2,
113.0, 91.9, 87.0.
cedure A. White powder, 419 mg, 1.90 mmol, 95% yield. M.p.
96-98 oC. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as elu-
ent for column chromatography. 1H NMR (500 MHz, DMSO-
d6) δ. 7.87 (d, J =8.5 Hz, 2H), 7.73-7.70 (m, 2H), 7.65 (t, J
=8.1 Hz, 1H), 7.49 (d, J =8.1 Hz, 1H), 7.18 (d, J =8.6 Hz, 2H).
13C{1H} NMR (126 MHz, DMSO-d6) δ 160.0, 155.1, 134.8,
131.8, 128.9, 125.2, 123.5, 118.8, 118.6, 117.9, 113.1, 106.1.
2-Bromo-4,5-dimethoxybenzonitrile (2y).18 Following the
Procedure A. White solid, 466 mg, 1.92 mmol, 96% yield.
M.p. 114-116 oC. Petroleum ether / ethyl acetate = 5 : 1 (v / v)
1
as eluent for column chromatography. H NMR (500 MHz,
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13
14
15
16
17
18
19
20
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22
23
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CDCl3) δ. 7.05 (s, 1H), 7.03 (s, 1H), 3.91 (s, 3H), 3.87 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 153.3, 148.6, 117.7, 117.6,
115.6, 115.3, 106.9, 56.6, 56.5.
Thiophene-2-carbonitrile (2ag).6 Following the Procedure A.
Colorless oil, 164 mg, 1.50 mmol, 75% yield. Petroleum ether
/ ethyl acetate = 10 : 1 (v / v) as eluent for column chromatog-
1
raphy. H NMR (500 MHz, CDCl3) δ 7.64-7.63 (m, 1H), 7.61
3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzonitrile
(d, J = 4.7 Hz, 1H), 7.14-7.13 (m, 1H). 13C{1H} NMR (126
MHz, CDCl3) δ 137.5, 132.7, 127.7, 114.3, 109.8.
(2z). Following the Procedure A. White solid, 469 mg, 1.96
o
mmol, 98% yield. M.p. 42-44 C. Petroleum ether / ethyl ace-
1
tate = 10 : 1 (v / v) as eluent for column chromatography. H
5-Nitrothiophene-2-carbonitrile (2ah).29 Following the Pro-
cedure A. A little brown solid, 252 mg, 1.64 mmol, 82% yield.
M.p. 38-40 oC. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as
eluent for column chromatography. 1H NMR (500 MHz,
CDCl3) δ 7.90 (d, J = 4.2 Hz, 1H), 7.58 (d, J = 4.1 Hz, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 155.7, 136.6, 127.7, 115.5,
112.1.
NMR (500 MHz, CDCl3) δ 7.26-7.22 (m, 2H), 7.19 (s, 1H),
6.70 (t, J = 74.5 Hz, 1H), 3.89 (d, J = 7.0 Hz, 2H), 1.32-1.23
(m, 1H), 0.68 (d, J = 7.8 Hz, 2H), 0.38 (d, J = 4.7 Hz, 2H).
19F{1H, 13C} NMR (471 MHz, CDCl3) -82.1 (d, J = 74.4 Hz,
2F). 13C{1H} NMR (126 MHz, CDCl3) δ 150.9, 144.0 (t, J =
2.7 Hz), 125.7, 122.9, 118.2, 117.4, 115.6 (t, J = 262 Hz),
110.1, 74.4, 10.0, 3.4. ESI-MS HRMS calculated for
C12H12F2NO2 [M+H]+ 240.0831, found: 240.0824.
Picolinonitrile (2ai).4a Following the Procedure A. A light
yellow oil, 196 mg, 1.88 mmol, 94% yield. Petroleum ether /
ethyl acetate = 3 : 1 (v / v) as eluent for column chromatog-
raphy. 1H NMR (500 MHz, CDCl3) δ 8.71 (d, J = 4.6 Hz, 1H),
7.85 (td, J1 = 8.0 Hz, J2 = 1.5 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H),
7.55-7.52 (m, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 151.2,
137.2, 134.0, 128.6, 127.1, 117.2.
1-Naphthonitrile (2aa).6 Following the Procedure A. Brown
solid, 303 mg, 1.98 mmol, 99% yield. M.p. 29-31 oC. Petrole-
um ether / ethyl acetate = 10 : 1 (v / v) as eluent for column
1
chromatography. H NMR (500 MHz, CDCl3) δ 8.19 (d, J =
8.2 Hz, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.89-7.85 (m, 2H), 7.65
(t, J = 7.0 Hz, 1H), 7.59 (t, J = 7.1 Hz, 1H), 7.47 (t, J = 7.5 Hz,
1H). 13C{1H} NMR (126 MHz, CDCl3) δ 133.2, 132.8, 132.5,
132.2, 128.6, 128.5, 127.5, 125.0, 124.9, 117.8, 110.0.
Quinoline-2-carbonitrile (2aj).4a Following the Procedure A.
A little brown solid, 296 mg, 1.92 mmol, 96% yield. M.p. 88-
o
90 C. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent
2-Naphthonitrile (2ab).6 Following the Procedure A. White
solid, 300 mg, 1.96 mmol, 98% yield. M.p. 62-64 oC. Petrole-
um ether / ethyl acetate = 10 : 1 (v / v) as eluent for column
for column chromatography. H NMR (500 MHz, CDCl3) δ
1
8.29 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.88 (d, J =
8.1 Hz, 1H), 7.82 (t, J = 7.5 Hz, 1H), 7.70-7.66 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3) δ 148.3, 137.6, 133.7, 131.4,
130.1, 129.6, 128.8, 127.9, 123.4, 11 7.7.
1
chromatography. H NMR (500 MHz, CDCl3) δ 8.20 (s, 1H),
7.91-7.87 (m, 3H), 7.66-7.58 (m, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 134.8, 134.3, 132.3, 129.3, 129.1, 128.5,
128.2, 127.8, 126.4, 119.4, 109.5.
1-Tosyl-1H-indole-3-carbonitrile (2ak).30 Following the
Procedure A. A little brown solid, 586 mg, 1.98 mmol, 99%
yield. M.p. 154-156 oC. Petroleum ether / ethyl acetate = 3 : 1
1-Bromo-2-naphthonitrile (2ac).26 Following the Procedure
A. White solid, 460 mg, 1.98 mmol, 99% yield. M.p. 88-90 oC.
Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
1
(v / v) as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 8.10 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.83 (d,
J = 7.7 Hz, 2H), 7.69 (d, J = 7.8 Hz, 1H), 7.45 (t, J = 7.5 Hz,
1H), 7.38 (t, J = 7.4 Hz, 1H), 7.30 (d, J = 7.8 Hz, 2H), 2.38 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 146.5, 134.2, 133.8,
133.3, 130.5, 128.5, 127.4, 126.7, 124.9, 120.4, 113.9, 113.6,
93.8, 21.8.
1
column chromatography. H NMR (500 MHz, CDCl3) δ 8.29
(d, J = 8.1 Hz, 1H), 7.88-7.85 (m, 2H), 7.71-7.66 (m, 2H),
7.56 (d, J = 8.4 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ
135.5, 131.8, 129.7, 129.1, 128.7, 128.6, 128.4, 127.5, 118.2,
113.6. Note: In the 13C{1H} NMR spectrum of 2ab, theoreti-
cally, there should be eleven peaks. Due to the compact over-
laying, it is difficult to specify the overlaying peaks.
Benzofuran-2-carbonitrile (2al).31 Following the Procedure
A. Yellow solid, 263 mg, 1.84 mmol, 92% yield. M.p. 30-32
oC. Petroleum ether / ethyl acetate = 10 : 1 (v / v) as eluent for
Tephthalonitrile (2ad).6 Following the Procedure A. White
solid, 240 mg, 1.88 mmol, 94% yield. M.p. 212-214 oC. Petro-
leum ether / ethyl acetate = 5 : 1 (v / v) as eluent for column
1
column chromatography. H NMR (500 MHz, CDCl3) δ 7.69
(d, J = 8.0 Hz, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.52 (t, J = 7.5
Hz, 1H), 7.46 (s, 1H), 7.37 (t, J = 7.0 Hz, 1H). 13C{1H} NMR
(126 MHz, CDCl3) δ 155.8, 128.6, 127.4, 125.6, 124.7, 122.7,
118.6, 112.2, 112.0.
1
chromatography. H NMR (500 MHz, DMSO-d6) δ 8.07 (s,
4H). 13C{1H} NMR (126 MHz, DMSO-d6) δ 133.2, 117.5,
115.7.
4-(Pyridin-2-yl)benzonitrile (2am).32 Following the Proce-
[1,1'-Biphenyl]-4,4'-dicarbonitrile (2ae).27 Following the
Procedure A. White solid, 400 mg, 1.96 mmol, 98% yield.
M.p. 237-239 oC. Petroleum ether / ethyl acetate = 3 : 1 (v / v)
dure A. White solid, 358 mg, 1.98 mmol, 99% yield. M.p. 95-
o
97 C. Petroleum ether / ethyl acetate = 5 : 1 (v / v) as eluent
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
1
as eluent for column chromatography. H NMR (500 MHz,
8.71 (d, J = 4.1 Hz, 1H), 8.10 (d, J = 8.2 Hz, 2H), 7.80 (t, J =
7.8 Hz, 1H), 7.76-7.73 (m, 3H), 7.30 (t, J = 5.6 Hz, 1H).
DMSO-d6) δ 7.98-7.95 (m, 8H). 13C{1H} NMR (126 MHz,
DMSO-d6) δ 142.7, 133.0, 128.1, 118.6, 111.3.
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13C{1H} NMR (126 MHz, CDCl3) δ 155.3, 150.1, 143.6, 137.2,
132.6, 127.5, 123.4, 121.1, 118.9, 112.5.
Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 132.3, 123.5,
118.9, 35.9, 30.0, 25.7, 25.3, 24.5, 19.4, 17.7.
Benzo[c][1,2,5]oxadiazole-4-carbonitrile (2an). Following
the Procedure A. Light yellow powder, 287 mg, 1.98 mmol,
99% yield. M.p. 91-93 oC. Petroleum ether / ethyl acetate = 5 :
Dodecanenitrile (4g).31 Following the Procedure B, the mix-
o
ture was stirred at 50 C for 5 h. Colorless oil, 341 mg, 1.88
mmol, 94% yield. Petroleum ether / ethyl acetate = 40 : 1 (v /
1
1
1 (v / v) as eluent for column chromatography. H NMR (500
v) as eluent for column chromatography. H NMR (500 MHz,
MHz, CDCl3) δ 8.17 (d, J = 9.2 Hz, 1H), 7.95 (d, J = 6.6 Hz,
1H), 7.58 (t, J = 8.1 Hz, 1H). 13C{1H} NMR (126 MHz,
CDCl3) δ 148.6, 147.4, 139.3, 130.6, 122.2, 113.8, 102.3. ESI-
MS HRMS calculated for C7H4N3O [M+H]+ 146.0349, found:
146.0343.
CDCl3) δ 2.31 (t, J = 7.0 Hz, 2H), 1.66-1.60 (m, 2H), 1.42-
1.41 (m, 2H), 1.27-1.25 (m, 14H), 0.86 (t, J = 6.5 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3) δ 119.9, 31.9, 29.6, 29.5,
29.3, 28.8, 28.7, 25.4, 22.7, 17.1, 14.1.Note: In the 13C{1H}
NMR spectrum of 4g, theoretically, there should be twelve
peaks. Due to the compact overlaying, it is difficult to specify
the overlaying peaks.
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4-Methyl-2-phenylpent-2-enenitrile (4a).33 Following the
Procedure A. A little yellow oil, 270 mg, 1,58 mmol, 79%
yield. Petroleum ether / ethyl acetate = 20 : 1 (v / v) as eluent
2-Phenylacetonitrile (4h).29 Following the Procedure A. Col-
orless oil, 162 mg, 1.38 mmol, 69% yield. Petroleum ether /
ethyl acetate = 10 : 1 (v / v) as eluent for column chromatog-
raphy. 1H NMR (500 MHz, CDCl3) δ 7.39 (t, J = 7.3 Hz, 2H),
7.34-7.33 (m, 3H), 3.74 (s, 2H). 13C{1H} NMR (126 MHz,
CDCl3) δ 130.0, 129.2, 128.1, 128.0, 118.0, 23.6.
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
7.43-7.40 (m, 2H), 7.38-7.34 (m, 3H), 6.42 (d, J = 10.7 Hz,
1H), 2.83-2.75 (m, 1H), 1.06 (d, J = 6.5 Hz, 6H). 13C{1H}
NMR (126 MHz, CDCl3) δ 156.0, 132.6, 128.9, 128.8, 128.5,
119.7, 113.3, 28.6, 22.1.
(E)-3-(4-Methoxyphenyl)acrylonitrile (4b).7f Following the
Procedure A. Off-white solid, 279 mg, 1.76 mmol, 88% yield.
M.p. 59-61 oC Petroleum ether / ethyl acetate = 10 : 1 (v / v) as
eluent for column chromatography. 1H NMR (500 MHz,
CDCl3) δ 7.39 (d, J = 8.7 Hz, 2H), 7.32 (d, J = 16.6 Hz, 1H),
6.91 (d, J = 8.5 Hz, 2H), 5.71 (d, J = 16.6 Hz, 1H), 3.84 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 162.2, 150.2, 129.2,
126.5, 118.8, 114.6, 93.5, 55.6.
3-([1,1'-Biphenyl]-4-yl)propanenitrile (4i).36 Following the
o
Procedure B, the mixture was stirred at 50 C for 3 h. White
solid, 381 mg, 1.84 mmol, 92% yield. M.p. 96-98 oC. Petrole-
um ether / ethyl acetate = 10 : 1 (v / v) as eluent for column
chromatography. 1H NMR (500 MHz, CDCl3) δ 7.60-7.58 (m,
4H), 7.46 (t, J = 7.3 Hz, 2H), 7.37 (t, J = 7.3 Hz, 1H), 7.32 (d,
J = 7.8 Hz, 2H), 3.01 (t, J = 7.4 Hz, 2H), 2.67 (t, J = 7.4 Hz,
2H). 13C{1H} NMR (126 MHz, CDCl3) δ 140.7, 140.4, 137.2,
128.9, 128.8, 127.7, 127.5, 127.2, 119.3, 31.3, 19.4.
(E)-2-methyl-3-phenylacrylonitrile (4c).31 Following the
Procedure A. A little yellow oil, 252 mg, 1.76 mmol, 88%
yield. Petroleum ether / ethyl acetate = 20 : 1 (v / v) as eluent
3-Phenylpropiolonitrile (4j).37 Following the Procedure A. A
o
clear solid, 213 mg, 1.68 mmol, 84% yield. M.p. 33-35 C.
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
Petroleum ether / ethyl acetate = 20 : 1 (v / v) as eluent for
1
7.42 (t, J = 7.0 Hz, 2H), 7.37 (t, J = 7.0 Hz, 1H), 7.33 (d, J =
7.5 Hz, 2H), 7.21 (s, 1H), 2.15 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 144.4, 134.1, 129.4, 129.3, 128.7, 121.3,
109.7, 16.8.
column chromatography. H NMR (500 MHz, CDCl3) δ 7.62
(d, J = 7.7 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.42 (t, J = 7.5 Hz,
2H). 13C{1H} NMR (126 MHz, CDCl3) δ 133.6, 132.0, 129.0,
117.7, 105.6, 83.1, 63.2.
(E)-dodec-2-enenitrile (4d).34 Following the Procedure B, the
Synthesis of 3,4-bis(2-methoxyethoxy)benzaldehyde (7).
3,4-bis(2-methoxyethoxy)benzaldehyde (7) was synthesized
according to a modified procedure:6 Under N2 atmosphere,
3,4-dihydroxybenzaldehyde 5 (2.0 g, 14.5 mmol), K2CO3 (8.0
g, 58 mmol) and DMF (13.2 mL, 1.1 M) were added to a 50
mL round bottom flask equipped with a stirring bar, then the
mixture was subjected to stir at room temperature for 1 h be-
fore 1-bromo-2-methoxyethane 6 (4.84 g, 34.8 mmol) was
introduced through the syringe. Then the reaction was allowed
o
mixture was stirred at 50 C for 5 h. Colorless oil, 325 mg,
1.82 mmol, 91% yield. Petroleum ether / ethyl acetate = 40 : 1
1
(v / v) as eluent for column chromatography. H NMR (500
MHz, CDCl3) δ 6.70 (dt, J1 = 16.3 Hz, J2 = 7.0 Hz, 1H), 5.30
(d, J = 16.3 Hz, 1H), 2.20 (q, J = 7.0 Hz, 2H), 1.44-1.40 (m,
2H), 1.29-1.25 (m, 12H), 0.86 (t, J = 7.0 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3) δ 156.2, 117.6, 99.7, 33.3, 31.9, 29.5,
29.31, 29.27, 29.0, 27.7, 22.7, 14.1.
o
(2E,4E)-dodeca-2,4-dienenitrile (4e).35 Following the Proce-
dure A. A little yellow oil, 316 mg, 1.78 mmol, 89% yield.
Petroleum ether / ethyl acetate = 40 : 1 (v / v) as eluent for
to react at 100 C for an additional 5 h. After completion, the
reaction diluted with water and extracted with dichloro-
methane (3× 30 mL). Then the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and concen-
trated to dryness. The residue was purified through silica gel
chromatography using a mixture of ethyl acetate and petrole-
um ether (v/v =1:3 to 1:2) as gradient eluent to afford the de-
sired product as yellow oil (2.6 g, 71% yield).
1
column chromatography. H NMR (500 MHz, CDCl3) δ 6.98-
6.93 (m, 1H), 6.13-6.12 (m, 2H), 5.22 (d, J = 16.0 Hz, 1H),
2.16-2.15 (m, 2H), 1.43-1.40 (m, 2H), 1.273-1.269 (m, 8H),
0.87 (t, J = 6.2 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ
151.0, 146.2, 128.0, 118.5, 96.5, 33.0, 31.8, 29.2, 29.1, 28.6,
22.7, 14.1.
Synthesis of 3,4-bis(2-methoxyethoxy)benzonitrile (8)6.
Aldehyde 7 (2.0 mmol, 1.0 eq.), H2NOH.HCl (153 mg, 2.2
mmol), Na2CO3 (117 mg, 1.1 mmol) and DMSO (10 mL, 0.2
M) were added into an oven-dried reaction tube (30 mL)
equipped with a stirring bar, and the reaction mixture reacted
at room temperature for 30 min. The reaction was monitored
by TLC. After the aldehyde 7 was completely consumed, an-
other portion of the Na2CO3 (1.06 g, 10 mmol) was added and
the reaction tube was covered with a plastic stopper before the
3,7-Dimethyloct-6-enenitrile (4f).7a Following the Procedure
o
B, the mixture was stirred at 50 C for 3 h. Colorless oil, 287
mg, 1.90 mmol, 95% yield. Petroleum ether / ethyl acetate =
1
40 : 1 (v / v) as eluent for column chromatography. H NMR
(500 MHz, CDCl3) δ 5.06 (t, J = 6.6 Hz, 1H), 2.31 (dd, J1 =
16.5 Hz, J2 = 5.3 Hz, 1H), 2.22 (dd, J1 = 16.6 Hz, J2 = 6.9 Hz,
1H), 2.03-1.96 (m, 2H), 1.88-1.81 (m, 1H), 1.67 (s, 3H), 1.59
(s, 3H), 1.48-1.41 (m, 1H), 1.36-1.31 (m, 1H), 1.06 (d, J = 6.7
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SO2F2 gas was introduced into the stirring reaction mixture
4-(4'-formyl-[1,1'-biphenyl]-4-yl)butanenitrile (11). White
by slow bubbling through a SO2F2 balloon at the room tem-
perature for an additional 12 h. After that, the reaction diluted
with water and extracted with dichloromethane (3× 20 mL).
Then the combined organic layers were washed with brine,
dried over anhydrous Na2SO4, and concentrated to dryness.
The residue was purified through silica gel chromatography
using a mixture of ethyl acetate and petroleum ether (v/v =1:3)
as eluent to afford the desired nitrile 8 as white gum, 487 mg,
solid, 170 mg, 0.68 mmol, 68% yield. M.p. 61-63 oC. Petrole-
um ether / ethyl acetate = 3 : 1 (v / v) as eluent for column
chromatography. 1H NMR (500 MHz, CDCl3) δ 10.05 (s, 1H),
7.94 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H), 7.59 (d, J =
8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.85 (t, J = 7.5 Hz, 2H),
2.37 (t, J = 7.0 Hz, 2H), 2.06-2.00 (m, 2H). 13C{1H} NMR
(126 MHz, CDCl3) δ 191.9, 146.8, 140.4, 138.1, 135.3, 130.4,
129.2, 127.7, 127.6, 119.4, 34.1, 26.9, 16.5. ESI-MS HRMS
calculated for C17H16NO [M+H]+ 250.1226, found: 250.1230.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
1.94 mmol, 97% yield. M.p. 39-40 C. H NMR (500 MHz,
CDCl3) δ 7.25 (d, J = 8.5 Hz, 1H), 7.13 (s, 1H), 6.92 (d, J =
8.4 Hz, 1H), 4.18 (t, J = 4.2 Hz, 2H), 4.15 (t, J = 4.1 Hz, 2H),
3.79-3.77 (m, 4H), 3.44 (s, 6H). 13C{1H} NMR (126 MHz,
CDCl3) δ 153.0, 149.0, 126.9, 119.2, 117.2, 113.6, 104.3, 70.9,
70.8, 69.2, 68.7, 59.4, 59.3.
4'-(3-cyanopropyl)-[1,1'-biphenyl]-4-carbonitrile
(12).
o
White solid, 42 mg, 0.17 mmol, 17% yield. M.p. 101-102 C.
Petroleum ether / ethyl acetate = 3 : 1 (v / v) as eluent for col-
1
umn chromatography. H NMR (500 MHz, CDCl3) δ 7.72 (d,
J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 8.0 Hz,
2H), 7.31 (d, J = 8.0 Hz, 2.0H), 2.85 (t, J = 7.5 Hz, 2H), 2.37
(t, J = 7.0 Hz, 2H), 2.06-2.01 (m, 2H). 13C{1H} NMR (126
MHz, CDCl3) δ 145.4, 140.6, 137.6, 132.7, 129.4, 127.7,
127.6, 119.4, 119.0, 111.1, 34.2, 26.9, 16.6. ESI-MS HRMS
calculated for C17H15N2 [M+H]+ 247.1230, found: 247.1243.
Synthesis of 5-(3-nitrophenyl)-1H-tetrazole (9).38 To a 30
mL reaction flask, 3-nitrobenzonitrile 2o (445 mg, 3 mmol),
NaN3 (293 mg, 4.5 mmol), NH4Cl (209 mg, 3.9 mmol) and
dry DMF (7.5 mL) were added and the mixture was allowed to
stir at 120 oC for about 4 h until the TLC showed the full con-
version of starting material. Then, the reaction mixture was
pour into water and extracted with dichloromethane (3× 20
mL). Then the combined organic layers were washed with
brine, dried over anhydrous Na2SO4, and concentrated to dry-
ness to afford the 5-(3-nitrophenyl)-1H-tetrazole 9 as white
solid (566 mg) in quantitative yield. And the structure and
purity of final product were identified by NMR. 1H NMR (500
MHz, DMSO-d6) δ 8.84 (s, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.42
(d, J = 8.2 Hz, 1H), 7.91 (t, J = 8.1 Hz, 1H).
4-(4'-(hydroxymethyl)-[1,1'-biphenyl]-4-yl)butanenitrile
(14). White solid, 168 mg, 0.67 mmol, 99% yield. M.p. 123-
125 oC. Petroleum ether / ethyl acetate = 2 : 1 (v / v) as eluent
1
for column chromatography. H NMR (500 MHz, CDCl3) δ
7.57 (d, J = 7.9 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.43 (d, J =
7.8 Hz, 2H), 7.25 (d, J = 7.8 Hz, 2H), 4.73 (s, 2H), 2.82 (t, J =
7.5 Hz, 2H), 2.35 (t, J = 7.0 Hz, 2H), 2.04-1.98 (m, 2H), 1.86
(s, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 140.3, 140.1,
139.3, 139.0, 129.0, 127.6, 127.4, 127.2, 119.6, 65.1, 34.1,
27.0, 16.5. ESI-MS HRMS calculated for C17H17NNaO
[M+Na]+ 274.1202, found: 274.1210.
Procedure for gram-scale example (2k). Aldehyde 1k (3.0 g,
20 mmol), H2NOH.HCl (1.53 g, 22 mmol), Na2CO3 (1.17 g, 11
mmol) and DMSO (100 mL, 0.2 M) were added into an oven-
dried round reaction bottle (250 mL) equipped with a stirring
bar, and the reaction mixture reacted at room temperature for
30 min. The reaction was monitored by TLC. After the alde-
hyde (1k) was completely consumed, another portion of the
Na2CO3 (10.6 g, 100 mmol) was added and the reaction bottle
was covered with a plastic stopper before the SO2F2 gas was
introduced into the stirring reaction mixture by slow bubbling
through a SO2F2 balloon at the room temperature for an addi-
tional 36 h. After that, the reaction diluted with water and ex-
tracted with dichloromethane (3× 40 mL). Then the combined
organic layers were washed with brine, dried over anhydrous
Na2SO4. Evaporation of solvent under reduced pressure to give
the target product 2k (2.94 g, 99% yield). And the structure
and purity of final product were identified by NMR.
Control experiments for mechanism investigation
General method: The yields were determined by HPLC using
pure 2a as the external standard (tR = 4.301 min, λmax = 248.8
nm, MeOH/H2O = 80 : 20 (v / v)).
Experiment a: 4-Benzyloxybenzaldehyde (1a, 0.2 mmol),
H2NOH.HCl (0.22 mmol, 1.1 eq.), Na2CO3 (0.11 mmol, 0.55
eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube and reacted at room temperature for 30 min. Then another
portion of Na2CO3 (1.0 mmol, 5.0 eq.) was added before
SO2F2 was introduced by bubbling into the mixture via a bal-
loon charged with needle, and the resulting mixture was al-
lowed to stir at r.t. for 12 h.
Experiment b: Aldoxime (I, 0.2 mmol), Na2CO3 (1.0 mmol,
5.0 eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube before SO2F2 was introduced by bubbling into the mixture
via a balloon charged with needle, and the resulting mixture
was allowed to stir at r.t. for 12 h.
Intramolecular Competition Experiment: Following the
modified procedure B in 1 mmol scale, the resulting mixture
was stirred at 50 oC for 3 h. Petroleum ether / ethyl acetate = 3 :
1 (v / v) as eluent for column chromatography to give the mix-
1
ture of nitriles 11 and 12 as white solid, 212 mg. H NMR
Experiment c: 4-Benzyloxybenzaldehyde (1a, 0.2 mmol),
H2NOH.HCl (0.22 mmol, 1.1 eq.), Na2CO3 (0.11 mmol, 0.55
eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube and reacted at room temperature for 30 min. Then another
portion of Na2CO3 (1.0 mmol, 5.0 eq.) was added and the re-
sulting mixture was allowed to stir at r.t. for 12 h.
(500 MHz, CDCl3) δ 10.05 (s, 1H), 7.95 (d, J = 8.2 Hz, 2H),
7.74 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.6 Hz, 0.5H), 7.67 (d, J
= 8.2 Hz, 0.5H), 7.59 (d, J = 8.1 Hz, 2H), 7.54 (d, J = 8.1 Hz,
0.5H), 7.31 (d, J = 8.1 Hz, 2.5H), 2.85 (t, J = 7.5 Hz, 2.5H),
2.37 (t, J = 7.0 Hz, 2.5H), 2.06-2.01 (m, 2.5H).
Note: The 4:1 ration was determined by the Proton NMR of
products 11 and 12 mixture. And the compound 12 was isolat-
ed from the mixture by treating the mixture with NaBH4 to
reduce the aldehyde 11 to the benzyl alcohol 14. Then the
oxidation of benzyl alcohol 14 generated pure product 11.
Experiment d: 4-Benzyloxybenzaldehyde (1a, 0.2 mmol),
H2NOH.HCl (0.22 mmol, 1.1 eq.), Na2CO3 (0.11 mmol, 0.55
eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube and reacted at room temperature for 30 min. Then SO2F2
was introduced by bubbling into the mixture via a balloon
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1983. (b) Larcok, R. C. Comprehensive Organic Transformations: A
charged with needle, and the resulting mixture was allowed to
stir at r.t. for 12 h.
Guide to Functional Group Preparations; VCH: New York, 1989. (c)
Smith, M. B.; March, J. March’s Advanced Organic Chemistry: Reac-
tions, Mechanisms, and Structure; Wiley, Hoboken, NJ, 6th edn, 2007.
(3) (a) Sandmeyer, T. Ueber die Ersetzung der Amidgruppe durch
Chlor in den aromatischen Substanzen. Ber. Dtsch. Chem. Ges. 1884,
17, 1633. (b) Nielsen, M. A.; Nielsen, M. K.; Pittelkow, A. Scale-Up
and Safety Evaluation of a Sandmeyer Reaction. Org. Process Res.
Dev. 2004, 8, 1059. (c) Rosenmund K. W.; Struck, E. Das am
Ringkohlenstoff gebundene Halogen und sein Ersatz durch andere
Substituenten. I. Mitteilung: Ersatz des Halogens durch die
Carboxylgruppe. Ber. Dtsch. Chem. Ges. B. 1919, 52, 1749. (d) Wang,
D. P.; Kuang, L. P.; Li, Z. W.; Ding, K. L-Proline-Promoted
Rosenmund-von Braun Reaction. Synlett 2008, 2008, 69. (e) Pradal, A.;
Evano, G. A vinylic Rosenmund–von Braun reaction: practical synthe-
sis of acrylonitriles. Chem. Commun. 2014, 50, 11907.
(4) (a) Zhang, X.; Xia, A.; Chen, H.; Liu, Y. General and Mild
Nickel-Catalyzed Cyanation of Aryl/Heteroaryl Chlorides with
Zn(CN)2: Key Roles of DMAP. Org. Lett. 2017, 19, 2118. (b) Arvela,
R. K.; Leadbeater, N. E. Rapid, Easy Cyanation of Aryl Bromides and
Chlorides Using Nickel Salts in Conjunction with Microwave Promo-
tion. J. Org. Chem. 2003, 68, 9122. (c) Sundermeier, M.; Zapf, A.;
Mutyala, S.; Baumann, W.; Sans, J.; Weiss, S.; Beller, M. Progress in
the Palladium‐Catalyzed Cyanation of Aryl Chlorides. Chem. Eur. J.
2003, 9, 1828. (d) Cristau, H.-J.; Ouali, A.; Spindler, J.-F.; Taillefer, M.
Mild and Efficient Copper-Catalyzed Cyanation of Aryl Iodides and
Bromides. Chem. Eur. J. 2005, 11, 2483. (e) Ushkov, A. V.; Grushin,
V. V. Rational Catalysis Design on the Basis of Mechanistic Under-
standing: Highly Efficient Pd-Catalyzed Cyanation of Aryl Bromides
with NaCN in Recyclable Solvents. J. Am. Chem. Soc. 2011, 133,
10999. (f) Anbarasan, P.; Schareina, T.; Beller, M. Recent develop
ments and perspectives in palladium-catalyzed cyanation of aryl hal-
ides: synthesis of benzonitriles. Chem. Soc. Rev. 2011, 40, 5049.
(5) Wu, Q.; Luo, Y.; Lei, A.; You, J. Aerobic Copper-Promoted
Radical-Type Cleavage of Coordinated Cyanide Anion: Nitrogen
Transfer to Aldehydes To Form Nitriles. J. Am. Chem. Soc. 2016, 138,
2885.
Experiment e: 4-Benzyloxybenzaldehyde (1a, 0.2 mmol),
H2NOH.HCl (0.22 mmol, 1.1 eq.), Na2CO3 (0.11 mmol, 0.55
eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube and reacted at room temperature for 30 min. Then SO2F2
was introduced by bubbling into the mixture via a balloon
charged with needle, and the resulting mixture was allowed to
stir at r.t. for 12 h. The reaction mixture was degassed with
gentle vacuum for about 3 minutes before the subsequent addi-
tion of Na2CO3 (1.0 mmol, 5.0 eq.) and the reaction mixture
further stirred at r.t. for another 12 h.
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Experiment f: 4-Benzyloxybenzaldehyde (1a, 0.2 mmol),
H2NOH.HCl (0.22 mmol, 1.1 eq.), Na2CO3 (0.11 mmol, 0.55
eq.) and DMSO (1.0 mL, 0.2 M) were added into a 20 mL
tube and reacted at room temperature for 30 min. Then another
portion of Na2CO3 (1.0 mmol, 5.0 eq.) was added and the stir-
ring lasted for 12 h at r.t. SO2F2 was subsequently introduced
by bubbling into the mixture via a balloon charged with needle,
and the resulting mixture was allowed to stir at r.t. for another
12 h.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
AUTHOR INFORMATION
Corresponding Author
(6) Hyodo, K.; Togashi, K.; Oishi, N.; Hasegawa, G.; Uchida, K.
Brønsted Acid Catalyzed Nitrile Synthesis from Aldehydes Using
Oximes via Transoximation at Ambient Temperature. Org. Lett. 2017,
19, 3005.
(7) (a) An, X.-D.; Yu, S. Direct Synthesis of Nitriles from Alde-
hydes Using an O-Benzoyl Hydroxylamine (BHA) as the Nitrogen
*E-mail: qinhuali@whut.edu.cn.
ORCID
Hua-Li Qin: 0000-0002-6609-0083
Notes
The authors declare no competing financial interest.
Source. Org. Lett. 2015, 17, 5064. (b) Laulhe ́, S.; Gori, S. S.; Nantz,
M. H. A Chemoselective, One-Pot Transformation of Aldehydes to
Nitriles. J. Org. Chem. 2012, 77, 9334. (c) Kelly, C. B.; Lambert, K.
M.; Mercadante, M. A.; Ovian, J. M.; Bailey, W. F.; Leadbeater, N. E.
Access to Nitriles from Aldehydes Mediated by an Oxoammonium
Salt. Angew. Chem., Int. Ed. 2015, 54, 4241. (d) Dornan, L. M.; Cao,
Q.; Flanagan, J. C. A.; Crawford, J. J.; Cook, M. J.; Muldoon, M. J.
Copper/TEMPO catalysed synthesis of nitriles from aldehydes or alco-
hols using aqueous ammonia and with air as the oxidant. Chem. Com-
mun. 2013, 49, 6030. (e) Noh, J.-H.; Kim, J. Aerobic Oxidative Con-
version of Aromatic Aldehydes to Nitriles Using a Nitroxyl/NOx Cata-
lyst System. J. Org. Chem. 2015, 80, 11624. (f) Rokade, B. V.; Prabhu,
K. R. Chemoselective Schmidt Reaction Mediated by Triflic Acid:
Selective Synthesis of Nitriles from Aldehydes. J. Org. Chem. 2012,
77, 5364.
(8) (a) Rapeyko, A.; Climent, M. J.; Corma, A.; Concepcion, P.;
Iborra, S. Nanocrystalline CeO2 as a Highly Active and Selective Cata-
lyst for the Dehydration of Aldoximes to Nitriles and One-Pot Synthe-
sis of Amides and Esters. ACS Catal. 2016, 6, 4564. (b) Hyodo, K.;
Kitagawa, S.; Yamazaki, M.; Uchida, K. Iron-Catalyzed Dehydration
of Aldoximes to Nitriles Requiring Neither Other Reagents Nor Nitrile
Media. Chem. Asian J. 2016, 11, 1348. (c) Yamaguchi, K.; Fujiwara,
H.; Ogasawara, Y.; Kotani, M.; Mizuno, N. A Tungsten–Tin Mixed
Hydroxide as an Efficient Heterogeneous Catalyst for Dehydration of
Aldoximes to Nitriles. Angew. Chem., Int. Ed. 2007, 46, 3922. (d)
Ishihara, K.; Furuya, Y.; Yamamoto, H. Rhenium(VII) Oxo Complex-
es as Extremely Active Catalysts in the Dehydration of Primary Am-
ides and Aldoximes to Nitriles. Angew. Chem., Int. Ed. 2002, 41, 2983.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of
China (Grant No. 21772150), the Wuhan applied fundamental
research plan of Wuhan Science and Technology Bureau (grant
NO. 2017060201010216) and Wuhan University of Technology
for the financial support.
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Note, Sulfuryl fluoride is a neurotoxic gas and also a particularly po-
tent greenhouse gas, please handle with care in fume hoods.
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