Acyl Cyanides as Bifunctional Reagent: Application in Copper-Catalyzed Cyanoamidation and Cyanoesterification Reaction

Article abstract of DOI:10.1021/acs.joc.9b03500

Cu-catalyzed domino decyanation and cyanation reaction of acyl cyanides with amines or alcohols have been developed. The cyano sources were generated in situ via C-CN cleavage yielding the corresponding cyano substituted amides or esters in moderate to excellent yields. This approach features a cheap copper catalyst, domino decyanation and cyanation reaction, readily available starting materials, broad substrate scope, operational simplicity, and the potential for further transformation of the cyano group.

Full text of DOI:10.1021/acs.joc.9b03500

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Note
Acyl Cyanides as Bifunctional Reagent: Application in Copper-
Catalyzed Cyanoamidation and Cyanoesterification Reaction
Zhengwang Chen,* Xiaowei Wen, Weiping Zheng, Ruolan He, Dou Chen, Dingsheng Cao, Lipeng Long,
and Min Ye*
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Supporting Information
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ABSTRACT: Cu-catalyzed domino decyanation and cyanation reaction of acyl cyanides with amines or alcohols have been
developed. The cyano sources were generated in situ via C−CN cleavage yielding the corresponding cyano substituted amides or
esters in moderate to excellent yields. This approach features a cheap copper catalyst, domino decyanation and cyanation reaction,
readily available starting materials, broad substrate scope, operational simplicity, and the potential for further transformation of the
cyano group.
ryl nitriles are among the most prevalent structural motifs
remarkable properties in acylcyanation of alkynes,7 decarbon-
Ain natural products, pharmaceuticals, dyes, and electronic ylative cyanation,8 arylation,9 cycloaddition,10 Strecker-type
addition reaction,11 and Passerini condensation.12 Although a
variety of transformations based on C−CN cleavage or C−CN
formation have been developed, the domino decyanation and
cyanation reaction of acyl cyanides has not been disclosed.13
This dual strategy meets today’s criteria of sustainable
synthesis and green chemistry, due to the simultaneous
formation of two important functional groups with a one-pot
operation from readily available materials. Herein, we
described the first copper-catalyzed highly efficient synthesis
of cyano substituted amides or esters via domino C−CN bond
cleavage and formation from the coupling of acyl cyanides and
amines or alcohols (Scheme 1).14
Initially, 2-iodoaniline 2a was selected as the representative
model substrate, and benzoyl cyanide 1a was employed as the
acylating agent and organic cyano-group source. As illustrated
in Table 1, three common transition-metal catalysts were
screened, and the cheap cupric oxide can furnish the N-(2-
cyanophenyl)benzamide 3a in good yield (Table 1, entries 1−
3). Then a wide range of copper catalysts were examined. All of
materials.1 They have emerged as ubiquitous building blocks
for various organic molecules such as amidines, amines,
amides, aldehydes, tetrazoles, acids, and heterocyclic com-
pounds.2 Therefore, it has attracted extensive interest to
develop new and efficient approaches for their preparation.
Traditional protocols toward aryl nitriles include the Rose-
nmund−von Braun reaction and Sandmeyer reaction, which
require a stoichiometric amount of highly toxic CuCN.3 In
recent years, transition-metal-catalyzed cyanation reaction of
aryl halides has made remarkable progress due to several
advantages, including wide substrate compatibility, mild
reaction conditions, high efficiency, and excellent selectivity.4
Compared to noble metal catalysts, copper catalysts are gaining
more attention owing to their low cost, wide availability,
exceptional reactivity, and sustainability.5 The cyanating agents
include a variety of metal cyanide sources, organic cyano-group
sources, and combined cyano-group sources.6 Although
significant progress has been made toward the synthesis of
aromatic nitriles, in view of the importance of cyano-
containing molecules and the limitation of the reported
approaches, further exploration of alternative and powerful
transformations to yield cyano-containing molecules remains a
challenge.
Received: December 28, 2019
Acyl cyanides, as readily available and versatile building
blocks, have been recognized as valuable substrates in organic
synthesis. They have attracted much attention owing to their
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A

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a
Scheme 1. Synthesis of Cyano Substituted Amides or Esters
from Acyl Cyanides and Amines or Alcohols
Scheme 2. Substrate Scope of Acyl Cyanides and Amines
a
Table 1. Optimization of the Reaction Conditions
b
entry
catalyst
solvent
temp
yield (%)
1
2
3
4
5
6
7
8
Pd(PPh3)4
FeCl3
CuO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DMSO
DMSO
130
130
130
130
130
130
130
130
130
130
130
130
130
110
70
62
n.p.
65
81
47
70
37
27
38
42
41
n.p.
91(88)
51
Cu2O
Cu(OTf)2
CuSO4·5H2O
Cu(OAc)2
CuCl2
CuBr2
CuI
Cu(NO3)2·3H2O
−
Cu2O
Cu2O
Cu2O
9
10
11
12
13
14
15
10
a
Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol) with catalyst
b
(10 mol %) in solvent 1.0 mL for 10 h. Determined by GC with
mesitylene as internal standard. n.p. = no product.
the catalysts had some effect on the reaction. Among the
catalyst tested, Cu2O was the most effective and delivered the
product in 81% yield (Table 1, entries 4−11). The reaction
could not occur without a catalyst (Table 1, entry 12).
Subsequently, a variety of solvents were investigated at 130 or
70 °C. The results revealed that the identity of the solvent was
important; DMSO proved to be the optimal solvent,
generating the desired product in 88% yield (Table S1 in the
Supporting Information, entries 1−7). Lowering the temper-
ature to 110 °C resulted in a lower yield, and a negligible yield
was observed at 70 °C (Table 1, entries 14−15). Finally,
because ligands can have a dramatic effect on the copper-
catalyzed cyanation reaction, some common ligands were tried
at 110 °C and found to be ineffective (Table S1 in the
Supporting Information, entries 8−10). The optimized
conditions for the synthesis of 3a employed Cu2O as the
catalyst and DMSO as the solvent at 130 °C for 10 h (Table 1,
entry 13).
a
Reaction conditions: acyl cyanide (0.2 mmol), amine (0.2 mmol),
b
Cu2O (10 mol %) and DMSO (1.0 mL) at 130 °C for 10 h. 2 mmol
scale. 3 equiv of 29% ammonia solution was used.
c
yields. The secondary aryl alkyl amine afforded 3h in low yield.
Substituted 2-aminopyridines reacted with 1a to give 3i and 3j
in 89% and 74% yields, respectively. Aroyl cyanides bearing
either an electron-donating or an electron-poor group on the
benzene ring were compatible and furnished the products in
moderate to good yields (3m−3s). Heteroaroyl cyanides
showed good reactivity to render the corresponding products
in satisfactory yields (3t and 3u). To our delight, the acetyl
cyanide and sterically hindered alkynoyl cyanide reacted
efficiently with aryl amines (3v−3x). Iodo-substituted benzoyl
cyanides were also evaluated, and a set of amines were
compatible under the standard conditions (3y−3ao). The
challenging primary amide was formed in 50% yield, when an
ammonia solution was employed as an amine source (3y). To
our surprise, tert-butyl amine gave the product in high yield
(3ab). The secondary amines led to the products in moderate
yields (3ag and 3ah). Besides, the desired products were
To explore the scope of the copper-catalyzed domino
decyanation and cyanation reaction, various substituted acyl
cyanides and amines were coupled, and the results were
summarized in Scheme 2. Benzoyl cyanide 1a reacted
efficiently with different iodo-substituted aromatic, heteroar-
omatic, and benzyl amines (3a−3l). Aniline with the iodo
group at different positions had negligible effect on the product
B
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obtained in good yields from p-toluidine (3ai and 3ao).
Unluckily, aniline with functionalities like CHO, COMe,
CONH2, and COOH did not afford the corresponding
products in this transformation (3ak−3an). To demonstrate
the practicality, a large-scale synthesis was examined, and 3a
was formed in 75% yield.
To further illustrate the operational viability of our
methodology, the coupling reaction of acyl cyanides with
alcohols was explored. As shown in Scheme 3, both electron-
rich and electron-deficient groups on the aroyl cyanide were
compatible for this transformation (4a−4i). Remarkably, α,β-
unsaturated acyl cyanide rendered the desired product in 45%
yield (4j). Iodo-substituted benzyl alcohols were beneficial for
the reaction compared to phenols (4a−4g). A variety of
primary and secondary aliphatic alcohols reacted successfully
with 4-iodo benzoyl cyanide (4k−4z). Significantly, TFE and
HFIP can be used as nucleophilic reagents to afford the fluoro-
containing products (4o and 4r). The unsaturated long chain
alcohol and cyclo alcohol delivered the products in satisfactory
yields (4t and 4u). Both 2-phenylethanol and phenylmethanol
were tolerable in this cyanoesterification in spite of the
electronic variations on the benzene rings (4v−4x). Ester 4z
could be obtained from the heteroaryl-substituted alcohol,
albeit in relatively low yield. Moreover, 3-iodo benzoyl cyanide
and sterically hindered 2-iodo benzoyl cyanide also led to the
desired products in high yields (4aa−4ad). These results
implied that the copper-catalyzed domino decyanation and
cyanation reaction can be effective for the cyano-substituted
amide and ester library.
a
Scheme 3. Substrate Scope of Acyl Cyanides and Alcohols
3-Cyano substituted pyridylamides are known to be an
important mGluR5 antagonist template.15 The target com-
pound 5a can be readily accessible via this copper-catalyzed
cyanoamidation reaction (Scheme 4a). The synthetic utility of
3a was demonstrated by preparation of the heterocycles, such
as quinazoline (5b)16 and benzoxazinone (5c),17 in good
yields (Scheme 4b).
Some control experiments were carried out to elucidate the
reaction mechanism (Scheme 5). The reaction of benzoyl
cyanide 1a with 2-iodoaniline 2a in the absence of a copper
catalyst could generate iodoarene 6a in excellent yield (Scheme
5a). Radical-trapping experiments were performed through the
addition of TEMPO, DPE, and BHT to the reaction system in
the standard conditions, and the formation of 3a was not
suppressed (Scheme 5b). These results inferred that this
transformation did not occur via a radical mechanism.
A tentative mechanism was proposed and shown in Scheme
6 on the basis of previous results and our experimental
observations. Initially, benzoyl cyanide 1a underwent nucleo-
philic addition−elimination with 2-iodoaniline 2a to lead to
intermediate 6a, in which the HCN was released through the
cleavage of the C−CN bond.13 It is noteworthy that the
hydrocyanic acid can be confirmed by the cyanide-detecting
test with a picric acid strip (Scheme S2 in the Supporting
Information).6d,18 Then the desired product 3a was generated
via a copper-catalyzed cyanation reaction from iodoarene and
HCN.19
a
Reaction conditions: acyl cyanide (0.2 mmol), alcohol (0.2 mmol),
In summary, we have developed the first copper-catalyzed
domino decyanation and cyanation reaction which allows the
Cu2O (10 mol %), and DMSO (1.0 mL) at 130 °C for 10 h.
Scheme 4. Synthetic Applications
C
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Scheme 5. Control Experiments
Scheme 6. Possible Reaction Mechanism
mg, 2 mmol), Cu2O (28.8 mg, 10 mol %), and DMSO (6.0 mL).
Then, the tube was placed in a preheated oil bath at 130 °C for 10 h.
After the solution cooled to room temperature, water (10 mL) was
added. The solution was extracted with ethyl acetate (3 × 10 mL),
and the combined extract was dried with anhydrous MgSO4. Solvent
was removed, and the residue was separated by column chromatog-
raphy (ethyl acetate/petroleum ether = 1:4) to give 3a (333 mg,
75%).
transfer of acyl cyanides to a series of cyano substituted amides
as well as esters. This transformation utilized the release of
hazardous HCN gas to generate valuable products. This dual
strategy the paved way for a new synthetic protocol for the
synthesis of bifunctional products in a one-pot operation.
Further investigation to extend the synthetic application and
detailed mechanism are currently ongoing in our laboratory.
N-(2-Cyanophenyl)benzamide (3a).17 White solid (39 mg, 88%);
mp 158−159 °C; Rf = 0.46 (petroleum ether/ethyl acetate = 4:1); 1H
NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 8.5 Hz, 1H), 8.43 (s, 1H),
7.95−7.92 (m, 2H), 7.67−7.58 (m, 3H), 7.56−7.50 (m, 2H), 7.22
(td, J = 7.7, 1.0 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ =
165.4, 140.5, 134.3, 133.6, 132.6, 132.1, 129.0, 127.1, 124.2, 121.1,
116.4, 102.1. MS (EI) m/z: 222, 105, 77, 51, 39.
EXPERIMENTAL SECTION
■
General Information. 1H and 13C{1H} NMR spectra were
obtained on a 400 and 100 MHz NMR spectrometer. The chemical
shifts are referenced to signals at 7.26 and 77.0 ppm, respectively, and
chloroform was used as the solvent with TMS as the internal standard
unless otherwise noted. Melting point (mp) values were determined
using a melting point instrument (uncorrected). Infrared (IR) spectra
were collected from an infrared spectrometer (Bruker Tensor 27).
Mass spectra were recorded on a GC-MS spectrometer at an
ionization voltage of 70 eV equipped with a DB-WAX capillary
column (internal diameter, 0.25 mm; length, 30 m). High resolution
mass spectra (HRMS) (TOF) were measured using electrospray
ionization (ESI) mass spectrometry. Silica gel (300−400 mesh) was
used for flash column chromatography, eluting (unless otherwise
stated) with an ethyl acetate/petroleum ether (PE) (60−90 °C)
mixture.
N-(3-Cyanophenyl)benzamide (3b).22 White solid (36 mg, 81%);
mp 138−139 °C; Rf = 0.32 (petroleum ether/ethyl acetate = 4:1); 1H
NMR (400 MHz, CDCl3): δ = 8.16 (s, 1H), 8.08−8.03 (m, 1H), 7.87
(dt, J = 8.4, 1.8 Hz, 3H), 7.60−7.55 (m, 1H), 7.51−7.47 (m, 2H),
7.45 (t, J = 5.6 Hz, 1H), 7.41 (dt, J = 7.7, 1.4 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 166.0, 138.8, 134.0, 132.3, 129.9, 128.8,
127.8, 127.1, 124.3, 123.3, 118.4, 112.9. MS (EI) m/z: 222, 105, 77,
51, 39.
N-(4-Cyanophenyl)benzamide (3c).23 White solid (40 mg, 90%);
mp 154−156 °C; Rf = 0.20 (petroleum ether/ethyl acetate = 4:1); 1H
NMR (400 MHz, CDCl3): δ = 8.19 (s, 1H), 7.90−7.84 (m, 2H), 7.80
(d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H),
7.50 (t, J = 7.5 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ =
165.9, 142.0, 134.0, 133.2, 132.4, 128.9, 127.1, 119.9, 118., 107.26.
MS (EI) m/z: 222, 105, 77, 51, 39.
The amines, alcohols, and acyl cyanides 1a, 1j were commercially
available from Sigma-Aldrich China. Substituted acyl cyanides 1b−1i,
1k−1o have been prepared using the literature procedure,20 and data
for known compounds have been compared with the reported
data.8−10,21 The typical experimental procedures for the preparation
of starting materials are given below.
General Procedure for the Synthesis of Cyano Substituted
Amides (3a−3aj). A mixture of acyl cyanide (0.2 mmol), amine (0.2
mmol) and Cu2O (2.9 mg, 10 mol %) in DMSO (1.0 mL) was placed
in a test tube (10 mL) equipped with a magnetic stirring bar. The
tube was placed in a preheated oil bath at 130 °C, and the mixture
was stirred vigorously for 10 h. After the reaction was finished, water
(5 mL) was added. The solution was extracted with ethyl acetate (3 ×
5 mL), and the combined extract was dried with anhydrous MgSO4.
Solvent was removed, and the residue was separated by column
chromatography to give the pure sample.
N-(3-Cyano-4-methylphenyl)benzamide (3d).24 Yellow solid (24
mg, 52%); mp 174−176 °C; Rf = 0. 51 (petroleum ether/ethyl acetate
1
= 2:1); H NMR (400 MHz, CDCl3): δ = 8.05 (s, 1H), 7.96 (d, J =
2.1 Hz, 1H), 7.86 (d, J = 7.3 Hz, 2H), 7.75 (dd, J = 8.4, 2.1 Hz, 1H),
7.57 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.29 (d, J = 8.4 Hz,
1H), 2.52 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.8,
137.8, 136.2, 134.1, 132.2, 130.8, 128.8, 127.0, 124.5, 123.6, 117.7,
113.1, 19.8. MS (EI) m/z: 236, 105, 77, 51.
N-(3-Cyano-5-fluorophenyl)benzamide (3e).25 Yellow solid (35
mg, 73%); mp 145−146 °C; Rf = 0.44 (petroleum ether/ethyl acetate
1
= 4:1); H NMR (400 MHz, CDCl3): δ = 8.37 (s, 1H), 7.93−7.82
Large Scale Synthesis. An oven-dried 25 mL screw cap test tube
was charged with a magnetic stir bar, 1a (262 mg, 2 mmol), 2a (438
(m, 3H), 7.70 (s, 1H), 7.61−7.54 (m, 1H), 7.47 (dd, J = 10.5, 4.7 Hz,
2H), 7.10 (ddd, J = 7.6, 2.4, 1.3 Hz, 1H). 13C{1H} NMR (100 MHz,
D
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CDCl3): δ = 166.1, 162.4 (d, J = 247 Hz), 140.6 (d, J = 11 Hz), 133.6,
132.6, 128.9, 127.1, 119.0 (d, J = 4 Hz), 117.4 (d, J = 4 Hz), 114.5 (d,
J = 25 Hz), 113.7 (d, J = 11 Hz), 112.2 (d, J = 26 Hz). MS (EI) m/z:
240, 207, 105, 77, 51, 39.
N-(4-Cyanobenzyl)-3-methylbenzamide (3n). Yellow solid (24
mg, 47%); mp 162−164 °C; Rf = 0.34 (petroleum ether/ethyl acetate
= 2:1); IR (KBr, cm−1) 3259, 3069, 2921, 2849, 2228, 1636, 1608,
1
1545, 1491, 1327, 1264, 1075, 795, 696, 542; H NMR (400 MHz,
N-(4-Cyano-3-fluorophenyl)benzamide (3f). Yellow solid (31 mg,
65%); mp 132−134 °C; Rf = 0.23 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3289, 3101, 2921, 2234, 1667, 1595, 1521,
CDCl3): δ = 7.67−7.60 (m, 3H), 7.59−7.55 (m, 1H), 7.45 (d, J = 8.4
Hz, 2H), 7.34 (dd, J = 3.8, 2.0 Hz, 2H), 6.58 (s, 1H), 4.70 (d, J = 6.1
Hz, 2H), 2.40 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 167.7,
143.8, 138.6, 133.7, 132.6, 132.5, 128.5, 128.2, 127.7, 123.8, 118.6,
111.3, 43.4, 21.3. MS (EI) m/z: 250, 235, 119, 91, 65, 39. HRMS
(ESI): calcd for C16H15N2O [M + H]+ 251.1179; found 251.1185.
4-(tert-Butyl)-N-(2-cyanophenyl)benzamide (3o). White solid (31
mg, 56%); mp 129−130 °C; Rf = 0.46 (petroleum ether/ethyl acetate
= 6:1); IR (KBr, cm−1) 3223, 3033, 2966, 2223, 1659, 1611, 1581,
1
1446, 1177, 1117, 874, 831, 719; H NMR (400 MHz, CDCl3): δ =
8.43 (s, 1H), 7.95−7.83 (m, 3H), 7.61−7.52 (m, 2H), 7.49 (t, J = 7.6
Hz, 2H), 7.41 (dd, J = 8.6, 1.8 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 166.1, 163.8 (d, J = 256 Hz), 144.2 (d, J = 11 Hz), 133.7,
133.6 (d, J = 11 Hz), 132.7, 128.9, 127.1, 115.5 (d, J = 3 Hz), 114.2,
107.5 (d, J = 25 Hz), 95.9 (d, J = 16 Hz). MS (EI) m/z: 240, 207,
105, 77, 51, 39. HRMS (ESI): calcd for C14H10FN2O [M + H]+
241.0772; found 241.0775.
1
1535, 1509, 1477, 1448, 1316, 1126, 1022, 853, 765, 710, 569; H
NMR (400 MHz, CDCl3): δ = 8.60 (d, J = 8.4 Hz, 1H), 8.42 (s, 1H),
7.92−7.84 (m, 2H), 7.68−7.59 (m, 2H), 7.57−7.50 (m, 2H), 7.20
(td, J = 7.7, 1.0 Hz, 1H), 1.36 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 165.3, 156.3, 140.7, 134.2, 132.0, 130.7, 127.0, 125.9,
124.0, 121.0, 116.4, 102.0, 35.0, 31.0. MS (EI) m/z: 278, 263, 245,
207, 192, 161, 146, 118, 91, 51, 41. HRMS (ESI): calcd for
C18H19N2O [M + H]+ 279.1492; found 279.1490.
N-(4-Cyano-2-nitrophenyl)benzamide (3g).26 Yellow solid (23
mg, 43%); mp = 145−147 °C; Rf = 0.57 (petroleum ether/ethyl
acetate = 4:1); 1H NMR (400 MHz, CDCl3): δ = 11.55 (s, 1H), 9.25
(d, J = 8.9 Hz, 1H), 8.62 (d, J = 2.0 Hz, 1H), 7.99 (dd, J = 5.3, 3.3 Hz,
2H), 7.94 (dd, J = 8.9, 1.9 Hz, 1H), 7.70−7.63 (m, 1H), 7.61−7.55
(m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.7, 138.9, 138.5,
135.5, 133.3, 133.0, 130.3, 129.2, 127.4, 122.6, 116.5, 106.7. MS (EI)
m/z: 267, 219, 105, 77, 51, 39.
N-(5-Cyanopyridin-2-yl)-4-methoxybenzamide (3p).29 Yellow
solid (30 mg, 60%); mp 144−146 °C; Rf = 0.26 (petroleum ether/
ethyl acetate = 4:1); 1H NMR (400 MHz, CDCl3): δ = 8.80 (s, 1H),
8.56−8.50 (m, 2H), 7.97 (dd, J = 8.8, 2.2 Hz, 1H), 7.92−7.88 (m,
2H), 7.02−6.97 (m, 2H), 3.89 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 165.1, 163.3, 154.2, 151.5, 141.5, 129.3, 125.3, 116.7,
114.2, 113.6, 104.8, 55.5. MS (EI) m/z: 253, 238, 135, 107, 92, 77,
64, 38.
N-(4-Cyanophenyl)-N-methylbenzamide (3h).27 Yellow solid (14
mg, 30%); mp 90−91 °C; Rf = 0.38 (petroleum ether/ethyl acetate =
2:1); 1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 8.7 Hz, 2H), 7.30
(ddd, J = 10.0, 7.1, 1.9 Hz, 3H), 7.25−7.20 (m, 2H), 7.13 (d, J = 8.7
Hz, 2H), 3.52 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 170.5,
148.8, 135.0, 133.0, 130.4, 128.6, 128.1, 126.9, 118.1, 109.6, 38.0. MS
(EI) m/z: 236, 129, 105, 77, 51, 39.
N-(4-Cyanobenzyl)-4-fluorobenzamide (3q). White solid (40 mg,
80%); mp 148−149 °C; Rf = 0.51 (petroleum ether/ethyl acetate =
1:1); IR (KBr, cm−1) 3269, 3070, 2921, 2849, 2235, 1633, 1578,
N-(4-Cyanopyridin-2-yl)benzamide (3i).28 White solid (40 mg,
89%); mp 141−142 °C; Rf = 0.25 (petroleum ether/ethyl acetate =
4:1); 1H NMR (400 MHz, CDCl3): δ = 8.95 (s, 1H), 8.72−8.69 (m,
1H), 8.38 (d, J = 5.0 Hz, 1H), 7.91 (dd, J = 5.2, 3.3 Hz, 2H), 7.63−
7.57 (m, 1H), 7.50 (dd, J = 10.4, 4.7 Hz, 2H), 7.28−7.25 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ = 165.8, 152.2, 149.0, 133.3,
132.7, 128.9, 127.2, 122.4, 121.1, 116.4, 116.1. MS (EI) m/z: 223,
194, 105, 77, 51, 39.
1
1506, 1454, 1319, 1301, 1154, 1094, 978, 886, 794, 597; H NMR
(400 MHz, CDCl3): δ = 7.84−7.77 (m, 2H), 7.60−7.54 (m, 2H),
7.40 (d, J = 8.5 Hz, 2H), 7.12−7.05 (m, 2H), 6.93 (s, 1H), 4.64 (d, J
= 6.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 166.5, 164.8
(d, J = 251 Hz), 143.8, 132.4, 129.8 (d, J = 3 Hz), 129.3 (d, J = 9 Hz),
128.1, 118.6, 115.7 (d, J = 22 Hz), 111.1, 43.4. MS (EI) m/z: 254,
224, 208, 123, 95, 75, 51, 39. HRMS (ESI): calcd for C15H12FN2O
[M + H]+ 255.0928; found 255.0927.
N-(5-Cyanopyridin-2-yl)benzamide (3j).29 Yellow solid (33 mg,
74%); mp 187−189 °C; Rf = 0.43 (petroleum ether/ethyl acetate =
4:1); 1H NMR (400 MHz, CDCl3): δ = 8.88 (s, 1H), 8.55 (d, J = 8.3
Hz, 2H), 8.00 (dd, J = 8.9, 2.0 Hz, 1H), 7.97−7.87 (m, 2H), 7.62 (dd,
J = 10.6, 4.2 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 165.7, 153.9, 151.6, 141.6, 133.2, 132.9, 129.0,
127.3, 116.7, 113.7, 105.1. MS (EI) m/z: 223, 194, 105, 77, 51, 39.
N-(3-Cyanobenzyl)benzamide (3k). White solid (37 mg, 78%);
mp 108−110 °C; Rf = 0.34 (petroleum ether/ethyl acetate = 2:1); IR
(KBr, cm−1) 3305, 3059, 2936, 2226, 1635, 1578, 1533, 1488, 1424,
N-(3-Cyanophenyl)- 2-chlorobenzamide (3r). Brown solid (29
mg, 58%); mp 66−67 °C; Rf = 0.53 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3243, 3060, 2861, 2228, 1655, 1583, 1550,
1
1327, 1258, 1178, 1099, 1050, 894, 883, 682, 653, 460; H NMR
(400 MHz, CDCl3) δ 8.40 (s, 1H), 8.03 (s, 1H), 7.79 (d, J = 7.8 Hz,
1H), 7.69−7.62 (m, 1H), 7.47−7.39 (m, 4H), 7.38−7.31 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ = 165.0, 138.4, 134.4, 132.0,
130.6, 130.4, 130.1, 129.9, 128.1, 127.3, 124.2, 123.2, 118.3, 113.0.
MS (EI) m/z: 256, 221, 192, 164, 139, 111, 90, 75, 50. HRMS (ESI):
calcd for C14H10ClN2O [M + H]+ 257.0476; found 257.0472.
Methyl 4-((2-Cyanophenyl)carbamoyl)benzoate (3s). White solid
(38 mg, 67%); mp 163−164 °C; Rf = 0.5 (petroleum ether/ethyl
acetate = 6:1); IR (KBr, cm−1) 3265, 3065, 2956, 2230, 1716, 1655,
1
1312, 1161, 1076, 800, 725, 693; H NMR (400 MHz, CDCl3): δ =
7.86−7.76 (m, 2H), 7.62−7.48 (m, 4H), 7.46−7.34 (m, 3H), 7.00 (s,
1H), 4.63 (d, J = 6.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ
= 167.6, 140.0, 133.6, 132.1, 131.8, 131.0, 130.9, 129.4, 128.6, 126.9,
118.6, 112.5, 43.0. MS (EI) m/z: 236, 131, 105, 77, 51, 39. HRMS
(ESI): calcd for C15H13N2O [M + H]+ 237.1022; found 237.1007.
N-(4-Cyanobenzyl)benzamide (3l).30 White solid (34 mg, 72%);
1
1603, 1580, 1533, 1494, 1285, 1106, 1019, 961, 777, 730, 502; H
NMR (400 MHz, CDCl3): δ = 8.51 (d, J = 8.4 Hz, 1H), 8.47 (s, 1H),
8.17−8.13 (m, 2H), 8.00−7.95 (m, 2H), 7.63 (ddd, J = 8.9, 6.7, 1.2
Hz, 2H), 7.23 (td, J = 7.7, 0.9 Hz, 1H), 3.95 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 165.9, 164.6, 140.1, 137.3, 134.2, 133.6,
132.2, 130.1, 127.2, 124.6, 121.5, 116.2, 102.7, 52.4. MS (EI) m/z:
280, 249, 224, 207, 192, 163, 135, 103, 76, 50, 39. HRMS (ESI): calcd
for C16H13N2O3 [M + H]+ 281.0921; found 281.0924.
1
mp 153−155 °C; Rf = 0.5 (petroleum ether/ethyl acetate = 1:1); H
NMR (400 MHz, CDCl3): δ = 7.85−7.76 (m, 2H), 7.62 (d, J = 8.2
Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.48−7.42 (m, 4H), 6.67 (s, 1H),
4.70 (d, J = 6.1 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ =
167.5, 143.8, 133.7, 132.5, 131.9, 128.7, 128.2, 126.9, 118.6, 111.3,
43.5. MS (EI) m/z: 236, 131, 105, 77, 51, 39.
N-(2-Cyanophenyl)-3-methylbenzamide (3m).17 White solid (37
mg, 79%); mp 144−145 °C; Rf = 0.44 (petroleum ether/ethyl acetate
N-(2-Cyanophenyl)thiophene-2-carboxamide (3t).31 Yellow solid
(40 mg, 87%); mp 142−143 °C; Rf = 0.28 (petroleum ether/ethyl
acetate = 5:1); 1H NMR (400 MHz, CDCl3): δ = 8.49 (d, J = 8.4 Hz,
1H), 8.30 (s, 1H), 7.70 (dd, J = 3.8, 1.0 Hz, 1H), 7.62 (ddd, J = 7.9,
6.4, 2.7 Hz, 3H), 7.23−7.17 (m, 1H), 7.15 (dd, J = 4.9, 3.9 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ = 159.7, 140.2, 138.1, 134.2,
132.1, 132.1, 129.0, 128.0, 124.2, 121.0, 116.3, 102.0. MS (EI) m/z:
228, 203, 111, 83, 63, 39.
1
= 4:1); H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 8.5 Hz, 1H),
8.39 (s, 1H), 7.75 (s, 1H), 7.73−7.68 (m, 1H), 7.67−7.60 (m, 2H),
7.43−7.38 (m, 2H), 7.21 (td, J = 7.7, 1.0 Hz, 1H), 2.45 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ = 165.6, 140.6, 139.0, 134.3,
133.6, 133.4, 132.1, 128.9, 127.9, 124.1, 124.0, 121.1, 116.4, 102.0,
21.4. MS (EI) m/z: 236, 207, 192, 119, 91, 65, 39.
E
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Note
6-Chloro-N-(2-cyanophenyl)nicotinamide (3u). Yellow solid (28
mg, 54%); mp 171−172 °C; Rf = 0.46 (petroleum ether/ethyl acetate
= 6:1); IR (KBr, cm−1) 3283, 3060, 2228, 1652, 1582, 1532, 1478,
1448, 1316, 1139, 961, 908, 864, 765, 649, 502; 1H NMR (400 MHz,
CDCl3): δ = 8.96 (d, J = 2.1 Hz, 1H), 8.42 (d, J = 8.2 Hz, 2H), 8.18
(dd, J = 8.3, 2.6 Hz, 1H), 7.70−7.62 (m, 2H), 7.48 (dd, J = 8.3, 0.5
Hz, 1H), 7.29−7.25 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ =
162.8, 155.3, 148.6, 139.7, 137.6, 134.3, 132.3, 128.3, 125.1, 124.6,
122.0, 116.2, 103.2. MS (EI) m/z: 257, 231, 207, 193, 155, 140, 112,
76, 50, 39. HRMS (ESI): calcd for C13H9ClN3O [M + H]+ 258.0429;
found 258.0425.
ethyl acetate = 4:1); IR (KBr, cm−1) 3265, 3065, 2971, 2935, 2845,
2230, 1636, 1609, 1540, 1498, 1457, 1322, 1299, 1288, 1074, 1021,
906, 856, 756, 693; 1H NMR (400 MHz, CDCl3): δ = 7.90−7.82 (m,
2H), 7.72−7.64 (m, 2H), 7.31 (d, J = 7.3 Hz, 1H), 7.26 (d, J = 3.7
Hz, 2H), 7.22 (dt, J = 8.6, 3.8 Hz, 1H), 6.67 (d, J = 8.1 Hz, 1H), 5.63
(q, J = 7.7 Hz, 1H), 3.02 (ddd, J = 15.9, 8.7, 4.0 Hz, 1H), 2.91 (dt, J =
16.0, 8.0 Hz, 1H), 2.71−2.60 (m, 1H), 1.92 (ddd, J = 15.9, 13.0, 8.1
Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.4, 143.4, 142.4,
138.2, 132.3, 128.2, 127.6, 126.8, 124.9, 123.9, 117.9, 114.9, 55.3,
33.81, 30.2. MS (EI) m/z: 262, 244, 217, 190, 147, 130, 116, 102, 91,
51, 39. HRMS (ESI): calcd for C17H14N2NaO [M + Na]+ 285.0998;
found 285.0993.
N-(3-Cyanophenyl)acetamide (3v).32 Yellow solid (16 mg, 51%);
mp = 130−132 °C; Rf = 0.42 (petroleum ether/ethyl acetate = 1:1);
1H NMR (400 MHz, CDCl3): δ = 8.34 (s, 1H), 7.96 (s, 1H), 7.72 (d,
J = 7.9 Hz, 1H), 7.45−7.31 (m, 2H), 2.19 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 169.2, 138.9, 129.8, 127.5, 123.9, 122.9,
118.5, 112.5, 24.3. MS (EI) m/z: 160, 131, 118, 91, 63, 43.
N-(5-Cyanopyridin-2-yl)acetamide (3w).33 Yellow solid (13 mg,
41%); mp 208−209 °C; Rf = 0.60 (petroleum ether/ethyl acetate =
4-Cyano-N-(4-fluorobenzyl)benzamide (3ae).38 White solid (29
mg, 57%); mp 109−111 °C; Rf = 0.72 (petroleum ether/ethyl acetate
1
= 1:1); H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.3 Hz, 2H),
7.74−7.64 (m, 2H), 7.29 (dd, J = 7.9, 5.7 Hz, 2H), 7.02 (t, J = 8.6 Hz,
2H), 6.73 (s, 1H), 4.58 (d, J = 5.7 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 165.5, 162.2 (d, J = 245 Hz), 138.0, 133.3 (d, J = 3
Hz), 132.4, 129.6 (d, J = 8 Hz), 127.6, 117.9, 115.7 (d, J = 22 Hz),
115.1, 43.5. MS (EI) m/z: 254, 224, 208, 190, 157, 130, 102, 75, 51,
39.
1
1:1); H NMR (400 MHz, CDCl3): δ = 8.54 (dd, J = 2.2, 0.7 Hz,
1H), 8.34 (d, J = 8.7 Hz, 1H), 8.26 (s, 1H), 7.93 (dd, J = 8.8, 2.2 Hz,
1H), 2.26 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 168.9,
153.7, 151.5, 141.6, 116.7, 113.4, 105.0, 24.8. MS (EI) m/z: 161, 119,
92, 64, 43.
4-Cyano-N-phenethylbenzamide (3af).38 White solid (36 mg,
73%); mp 115−117 °C; Rf = 0.72 (petroleum ether/ethyl acetate =
1:1); 1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 8.2 Hz, 2H), 7.69
(d, J = 8.2 Hz, 2H), 7.34 (t, J = 7.3 Hz, 2H), 7.30−7.25 (m, 1H), 7.22
(d, J = 7.3 Hz, 2H), 6.39 (s, 1H), 3.72 (q, J = 6.7 Hz, 2H), 2.94 (t, J =
6.9 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.6, 138.4,
132.3, 128.7, 128.6, 127.5, 126.7, 117.9, 114.8, 41.2, 35.3. MS (EI) m/
z: 250, 207, 173, 159, 130, 104, 91, 65, 39.
N-(2-Cyanophenyl)pivalamide (3x). White solid (19 mg, 47%);
mp 79−80 °C; Rf = 0.48 (petroleum ether/ethyl acetate = 6:1); IR
(KBr, cm−1) 3284, 3065, 2974, 2231, 1671, 1601, 1577, 1472, 1300,
1177, 1029, 940, 813, 755, 721, 629, 481; 1H NMR (400 MHz,
CDCl3): δ = 8.40 (d, J = 8.3 Hz, 1H), 7.96 (s, 1H), 7.57 (dd, J = 12.8,
4.5 Hz, 2H), 7.14 (t, J = 7.6 Hz, 1H), 1.35 (s, 9H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 176.9, 140.7, 134.0, 131.8, 123.8, 121.0,
116.3, 102.0, 40.1, 27.3. MS (EI) m/z: 202, 187, 159, 145, 118, 85,
57, 41. HRMS (ESI): calcd for C12H15N2O [M + H]+ 203.1179;
found 203.1171.
4-Cyano-N,N-dipropylbenzamide (3ag).39 Colorless liquid (32
mg, 70%); Rf = 0.35 (petroleum ether/ethyl acetate = 4:1); 1H NMR
(400 MHz, CDCl3): δ = 7.72−7.67 (m, 2H), 7.48−7.43 (m, 2H),
3.51−3.38 (m, 2H), 3.17−3.04 (m, 2H), 1.72−1.66 (m, 2H), 1.58−
1.46 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H), 0.74 (t, J = 7.3 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ = 169.6, 141.6, 132.3, 127.1,
118.1, 112.8, 50.5, 46.3, 21.8, 20.5, 11.3, 10.9. MS (EI) m/z: 230, 201,
159, 130, 102, 75, 51.
4-Cyanobenzamide (3y).6d Yellow solid (15 mg, 50%); mp 224−
1
225 °C; Rf = 0.2 (petroleum ether/ethyl acetate = 1:1); H NMR
(400 MHz, DMSO-d6): δ = 8.21 (s, 1H), 8.06−7.99 (m, 2H), 7.98−
7.92 (m, 2H), 7.68 (s, 1H). 13C{1H} NMR (100 MHz, DMSO-d6): δ
= 166.4, 138.2, 132.3, 128.2, 118.3, 113.6. MS (EI) m/z: 146, 130,
102, 75, 50, 44.
4-(Morpholine-4-carbonyl)benzonitrile (3ah).40 Yellow solid (23
mg, 55%); mp 143−145 °C; Rf = 0. 32 (petroleum ether/ethyl acetate
= 1:1); 1H NMR (400 MHz, CDCl3): δ = 7.76−7.69 (m, 2H), 7.54−
7.47 (m, 2H), 3.70 (d, J = 64.9 Hz, 6H), 3.37 (s, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 168.2, 139.5, 132.4, 127.7, 117.9, 113.6, 66.6,
48.0, 42.5. MS (EI) m/z: 216, 185, 130, 102, 86, 56, 42.
4-Cyano-N-methylbenzamide (3z).34 White solid (18 mg, 56%);
mp 209−210 °C; Rf = 0.22 (petroleum ether/ethyl acetate = 1:1); 1H
NMR (400 MHz, DMSO-d6): δ = 8.72 (d, J = 4.0 Hz, 1H), 8.02−
7.94 (m, 4H), 2.80 (d, J = 4.6 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 166.3, 138.4, 132.4, 127.5, 117.9, 114.9, 27.0. MS (EI)
m/z: 160, 130, 102, 75, 51, 39.
4-Cyano-N-(p-tolyl)benzamide (3ai).41 Yellow solid (38 mg,
80%); mp 177−179 °C; Rf = 0.36 (petroleum ether/ethyl acetate =
4:1); 1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.1 Hz, 3H), 7.74
(d, J = 8.0 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H),
2.35 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 163.8, 138.9,
134.9, 134.6, 132.5, 129.6, 127.7, 120.4, 117.9, 115.1, 20.9. MS (EI)
m/z: 236, 207, 192, 130, 102, 77, 51, 39.
4-Cyano-N-cyclohexylbenzamide (3aa).35 White solid (29 mg,
64%); mp 183−184 °C; Rf = 0.3 (petroleum ether/ethyl acetate =
4:1); 1H NMR (400 MHz, CDCl3): δ = 7.88−7.82 (m, 2H), 7.72 (d,
J = 7.9 Hz, 2H), 6.03 (s, 1H), 4.02−3.90 (m, 1H), 2.08−1.97 (m,
2H), 1.82−1.72 (m, 2H), 1.66 (dd, J = 9.0, 3.9 Hz, 2H), 1.42 (dd, J =
24.9, 12.4 Hz, 2H), 1.24−1.13 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 164.8, 138.9, 132.3, 127.5, 118.0, 114.8, 49.1, 33.0, 25.4,
24.8. MS (EI) m/z: 228, 199, 185, 147, 130, 102, 82, 67, 41.
N-(tert-Butyl)-4-cyanobenzamide (3ab).36 White solid (33 mg,
82%); mp 146−147 °C; Rf = 0.4 (petroleum ether/ethyl acetate =
N-(4-Bromophenyl)-4-cyanobenzamide (3aj).42 White solid (28
mg, 47%); mp 205−207 °C; Rf = 0. 64 (petroleum ether/ethyl acetate
= 2:1); 1H NMR (400 MHz, DMSO-d6): δ = 10.60 (s, 1H), 8.09 (d,
J = 8.5 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H), 7.79−7.73 (m, 2H), 7.54
(d, J = 8.8 Hz, 2H). 13C{1H} NMR (100 MHz, DMSO-d6): δ =
164.69, 139.12, 138.61, 132.93, 131.99, 129.02, 122.75, 118.75,
116.30, 114.45. MS (EI) m/z: 300, 130, 102, 75, 63, 44.
1
4:1); H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.3 Hz, 2H),
7.71−7.59 (m, 2H), 6.10 (s, 1H), 1.45 (s, 9H). 13C{1H} NMR (100
MHz, CDCl3): δ = 165.0, 139.7, 132.2, 127.4, 118.0, 114.4, 52.0, 28.6.
MS (EI) m/z: 202, 187, 147, 130, 102, 75, 56, 41.
3-Cyano-N-(p-tolyl)benzamide (3ao). Yellow solid (31 mg, 66%);
mp 166−167 °C; Rf = 0.25 (petroleum ether/ethyl acetate = 4:1); IR
(KBr, cm−1) 3307, 3062, 2916, 2232, 1652, 1596, 1579, 1521, 1402,
N-Benzyl-4-cyanobenzamide (3ac).37 White solid (32 mg, 68%);
mp 150−151 °C; Rf = 0.62 (petroleum ether/ethyl acetate = 1:1); 1H
NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.2 Hz, 2H), 7.67 (dd, J =
8.4, 1.5 Hz, 2H), 7.34 (dd, J = 8.0, 6.2 Hz, 2H), 7.32−7.27 (m, 3H),
6.85 (s, 1H), 4.60 (d, J = 5.6 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 165.5, 138.1, 137.4, 132.3, 128.7, 127.7, 127.7, 127.6,
117.9, 114.9, 44.2. MS (EI) m/z: 236, 219, 190, 157, 130, 102, 79, 51,
39.
1
1297, 1184, 1021, 935, 809, 795, 693, 518; H NMR (400 MHz,
CDCl3): δ = 8.16 (s, 1H), 8.14−8.03 (m, 2H), 7.80 (dt, J = 7.7, 1.2
Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.50 (d, J = 8.2 Hz, 2H), 7.17 (d, J
= 8.3 Hz, 2H), 2.34 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ =
163.5, 136.2, 134.9, 134.7, 134.7, 131.5, 130.7, 129.7, 129.6, 120.6,
118.0, 112.8, 20.9. MS (EI) m/z: 236, 205, 192, 165, 130, 102, 77, 51,
39. HRMS (ESI): calcd for C15H13N2O [M + H]+ 237.1022; found
237.1016.
4-Cyano-N-(2,3-dihydro-1H-inden-1-yl)benzamide (3ad). Gray
solid (38 mg, 73%); mp 146−148 °C; Rf = 0.31 (petroleum ether/
General Procedure for the Synthesis of Cyano Substituted
Esters (4a−4ad). A mixture of acyl cyanide (0.2 mmol), alcohol (0.2
F
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Note
mmol), and Cu2O (2.9 mg, 10 mol %) in DMSO (1.0 mL) was placed
in a test tube (10 mL) equipped with a magnetic stirring bar. The
tube was placed in a preheated oil bath at 130 °C, and the mixture
was stirred vigorously for 10 h. After the reaction was finished, water
(5 mL) was added. The solution was extracted with ethyl acetate (3 ×
5 mL), and the combined extract was dried with anhydrous MgSO4.
Solvent was removed, and the residue was separated by column
chromatography to give the pure sample.
2H), 3.85 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.6,
163.6, 139.6, 133.0, 132.9, 131.8, 129.3, 128.6, 121.7, 117.0, 113.6,
112.0, 63.8, 55.3. MS (EI) m/z: 267, 224, 206, 180, 152, 135, 116, 92,
77, 64, 39. HRMS (ESI): calcd for C16H14NO3 [M + H]+ 268.0968;
found 268.0962.
2-Cyanobenzyl 4-Fluorobenzoate (4h). White solid (30 mg,
58%); mp 62−64 °C; Rf = 0.54 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3066, 2918, 2849, 2226, 1724, 1604, 1506,
4-Cyanophenyl Benzoate (4a).43 White solid (29 mg, 66%); mp
1487, 1457, 1270, 1124, 1010, 799, 763, 613; H NMR (400 MHz,
1
1
95−96 °C; Rf = 0.6 (petroleum ether/ethyl acetate = 4:1); H NMR
CDCl3): δ = 8.16−8.05 (m, 2H), 7.73 (d, J = 7.5 Hz, 1H), 7.66−7.58
(m, 2H), 7.50−7.43 (m, 1H), 7.16−7.08 (m, 2H), 5.53 (s, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 165.9 (d, J = 253 Hz), 165.0,
139.2, 133.1 (d, J = 20 Hz), 132.4, 132.3, 129.5, 128.9, 125.7 (d, J = 3
Hz), 117.0, 115.6 (d, J = 22 Hz), 112.3, 64.3. MS (EI) m/z: 255, 237,
208, 183, 160, 132, 123, 116, 95, 75, 63, 39. HRMS (ESI): calcd for
C15H10FNNaO2 [M + Na]+ 278.0588; found 278.0586.
(400 MHz, CDCl3): δ = 8.23−8.16 (m, 2H), 7.79−7.72 (m, 2H),
7.71−7.65 (m, 1H), 7.57−7.51 (m, 2H), 7.41−7.35 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 164.3, 154.2, 134.1, 133.7,
130.2, 128.7, 122.9, 118.2, 116.4, 109.8. MS (EI) m/z: 223, 207, 193,
166, 140, 105, 77, 51, 39.
2-Cyanobenzyl Benzoate (4b). White solid (39 mg, 82%); mp
52−53 °C; Rf = 0.52 (petroleum ether/ethyl acetate = 4:1); IR (KBr,
cm−1) 3069, 2922, 2224, 1716, 1601, 1584, 1528, 1489, 1376, 1176,
1123, 1025, 765, 713, 559; 1H NMR (400 MHz, CDCl3): δ = 8.10 (d,
J = 7.2 Hz, 2H), 7.72 (d, J = 7.7 Hz, 1H), 7.62 (d, J = 4.1 Hz, 2H),
7.57 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 3H), 5.55 (s, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 165.9, 139.4, 133.2, 133.0,
132.9, 129.7, 129.4, 129.4, 128.7, 128.4, 117.0, 112.1, 64.1. MS (EI)
m/z: 237, 219, 192, 165, 132, 105, 77, 51, 39. HRMS (ESI): calcd for
C15H12NO2 [M + H]+ 238.0863; found 238.0863.
2-Cyanobenzyl 2-Chlorobenzoate (4i). Brown solid (30 mg,
56%); mp 136−139 °C; Rf = 0.47 (petroleum ether/ethyl acetate =
1:1); IR (KBr, cm−1) 3088, 2919, 2849, 2231, 1725, 1647, 1590,
1
1567, 1471, 1377, 1297, 1115, 1051, 768, 709, 551; H NMR (400
MHz, CDCl3) δ 7.93 (dd, J = 7.8, 1.2 Hz, 1H), 7.76−7.69 (m, 1H),
7.64 (qd, J = 8.0, 3.7 Hz, 2H), 7.53−7.39 (m, 3H), 7.37−7.28 (m,
1H), 5.55 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.0,
139.0, 134.1, 133.1, 133.0, 132.9, 131.8, 131.2, 130.0, 129.2, 129.0,
126.7, 117.0, 112.4, 64.7. MS (EI) m/z: 271, 236, 190, 165, 139, 116,
75, 50, 39. HRMS (ESI): calcd for C15H11ClNO2 [M + H]+
272.0473; found 272.0467.
4-Cyanophenyl 3-Methylbenzoate (4c). Yellow solid (28 mg,
59%); mp 62−64 °C; Rf = 0.63 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3103, 2917, 2849, 2231, 1729, 1600, 1585,
2-Cyanobenzyl Cinnamate (4j). Yellow solid (24 mg, 45%); mp
61−62 °C; Rf = 0.47 (petroleum ether/ethyl acetate = 4:1); IR (KBr,
cm−1) 3088, 2919, 2849, 2231, 1725, 1590, 1590, 1567, 1471, 1253,
1115, 1051, 901, 768, 728, 651, 551; 1H NMR (400 MHz, CDCl3): δ
= 7.77 (d, J = 16.0 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.65−7.57 (m,
2H), 7.53 (dt, J = 7.9, 3.3 Hz, 2H), 7.45 (td, J = 7.4, 1.7 Hz, 1H),
7.41−7.36 (m, 3H), 6.50 (d, J = 16.0 Hz, 1H), 5.44 (s, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 166.3, 145.9, 139.5, 134.2, 133.0,
132.9, 130.5, 129.4, 128.9, 128.7, 128.1, 117.1, 112.2, 99.9, 63.7. MS
(EI) m/z: 263, 235, 219, 192, 148, 131, 103, 77, 51, 39. HRMS (ESI):
calcd for C17H13NNaO2 [M + Na]+ 286.0838; found 286.0830.
Phenyl 4-Cyanobenzoate (4k).43 White solid (30 mg, 68%); mp
1
1500, 1458, 1278, 1212, 1087, 866, 833, 733, 681, 553; H NMR
(400 MHz, CDCl3): δ = 8.04−7.96 (m, 2H), 7.78−7.71 (m, 2H),
7.48 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.39−7.34 (m, 2H),
2.45 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 164.4, 154.2,
138.6, 134.9, 133.7, 130.7, 128.6, 128.5, 127.4, 122.9, 118.2, 109.7,
21.2. MS (EI) m/z: 237, 207, 178, 165, 139, 119, 91, 65, 39. HRMS
(ESI): calcd for C15H12NO2 [M + H]+ 238.0863; found 238.0864.
2-Cyanobenzyl 3-methylbenzoate (4d). Colorless liquid (34 mg,
68%); Rf = 0.62 (petroleum ether/ethyl acetate = 4:1); IR (KBr,
cm−1) 3065, 2957, 2923, 2851, 2227, 1719, 1603, 1590, 1489, 1452,
1
1379, 1273, 1194, 1080, 1002, 763, 743, 682; H NMR (400 MHz,
1
165−166 °C; Rf = 0.64 (petroleum ether/ethyl acetate = 4:1); H
CDCl3): δ = 7.89 (d, J = 6.9 Hz, 2H), 7.72 (d, J = 7.7 Hz, 1H), 7.62
(d, J = 4.0 Hz, 2H), 7.49−7.42 (m, 1H), 7.40−7.30 (m, 2H), 5.55 (s,
2H), 2.40 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 166.2,
139.5, 138.3, 134.1, 133.1, 132.9, 130.3, 129.4, 128.7, 128.3, 126.9,
123.1, 117.0, 112.2, 64.0, 21.2. MS (EI) m/z: 251, 233, 222, 190, 160,
132, 119, 91, 65, 39. Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21;
N, 5.57. Found: C, 76.20; H, 5.27; N, 5.65.
NMR (400 MHz, CDCl3): δ = 8.34−8.27 (m, 2H), 7.84−7.77 (m,
2H), 7.49−7.42 (m, 2H), 7.35−7.27 (m, 1H), 7.25−7.18 (m, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 163.4, 150.3, 133.2, 132.2,
130.4, 129.5, 126.2, 121.3, 117.7, 116.7. MS (EI) m/z: 223, 193, 164,
130, 102, 75, 65, 51, 39.
Methyl 4-Cyanobenzoate (4l).45 Yellow solid (30 mg, 93%); mp
62−63 °C; Rf = 0.54 (petroleum ether/ethyl acetate = 4:1); 1H NMR
(400 MHz, CDCl3): δ = 8.12 (d, J = 8.6 Hz, 2H), 7.73 (d, J = 8.6 Hz,
2H), 3.94 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 165.3,
133.8, 132.1, 130.0, 117.8, 116.2, 52.6. MS (EI) m/z: 161, 130, 102,
75, 51, 38.
2-Cyanobenzyl 4-(tert-butyl)benzoate (4e). Colorless liquid (28
mg, 47%); Rf = 0.57 (petroleum ether/ethyl acetate = 4:1); IR (KBr,
cm−1) 3056, 2964, 2869, 2227, 1723, 1608, 1571, 1452, 1314, 1271,
1189, 1115, 1017, 854, 774, 707, 547; 1H NMR (400 MHz, CDCl3):
δ = 8.07−7.95 (m, 2H), 7.76−7.66 (m, 1H), 7.61 (d, J = 4.2 Hz, 2H),
7.50−7.38 (m, 3H), 5.54 (s, 2H), 1.33 (d, J = 4.3 Hz, 9H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 166.0, 157.0, 139.7, 133.1, 132.9,
129.7, 129.3, 128.6, 126.7, 125.4, 117.0, 112.1, 63.9, 35.1, 31.0. MS
(EI) m/z: 293, 278, 260, 232, 218, 177, 161, 145, 116, 89, 51, 41.
HRMS (ESI): calcd for C19H20NO2 [M + H]+ 294.1489; found
294.1486.
Ethyl 4-Cyanobenzoate (4m).46 White solid (27 mg, 78%); mp
54−55 °C; Rf = 0.62 (petroleum ether/ethyl acetate = 4:1); 1H NMR
(400 MHz, CDCl3): δ = 8.14 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.6 Hz,
2H), 4.41 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 164.9, 134.2, 132.1, 130.0, 117.9,
116.2, 61.7, 14.2. MS (EI) m/z: 175, 147, 130, 102, 75, 51, 45.
2,2-Difluoroethyl 4-Cyanobenzoate (4n). White solid (32 mg,
75%); mp 54−55 °C; Rf = 0.50 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3103, 3053, 3020, 2973, 2232, 1736, 1609,
1566, 1501, 1460, 1372, 1274, 1020, 907, 868, 765, 691, 591, 485; 1H
NMR (400 MHz, CDCl3): δ = 8.20−8.12 (m, 2H), 7.80−7.72 (m,
2H), 6.09 (tt, J = 54.8, 3.9 Hz, 1H), 4.54 (td, J = 13.7, 3.9 Hz, 2H).
13C{1H} NMR (100 MHz, CDCl3): δ = 164.0, 132.5, 132.3, 130.3,
117.7, 117.0, 112.4 (t, J = 40 Hz), 63.2 (t, J = 29 Hz). MS (EI) m/z:
211, 147, 130, 102, 75, 51, 45. HRMS (ESI): calcd for C10H8F2NO2
[M + H]+ 212.0518; found 212.0520.
4-Cyanophenyl 4-Methoxybenzoate (4f).44 White solid (25 mg,
50%); mp 109−110 °C; Rf = 0.47 (petroleum ether/ethyl acetate =
1
4:1); H NMR (400 MHz, CDCl3): δ = 8.18−8.10 (m, 2H), 7.77−
7.69 (m, 2H), 7.39−7.32 (m, 2H), 7.04−6.97 (m, 2H), 3.91 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ = 164.3, 164.0, 154.4, 133.6,
132.4, 122.9, 120.8, 118.3, 114.0, 109.5, 55.5. MS (EI) m/z: 253,
2326, 207, 184, 164, 135, 107, 92, 77, 64, 39.
2-Cyanobenzyl 4-Methoxybenzoate (4g). White solid (38 mg,
72%); mp 66−67 °C; Rf = 0.49 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3073, 2983, 2847, 2222, 1705, 1607, 1582,
1
1511, 1457, 1382, 1286, 1021, 846, 764, 695, 522; H NMR (400
2,2,2-Trifluoroethyl 4-Cyanobenzoate (4o). Gray solid (33 mg,
73%); mp 63−64 °C; Rf = 0.64 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3103, 3053, 3020, 2973, 2232, 1736, 1609,
MHz, CDCl3): δ = 8.07−8.01 (m, 2H), 7.70 (d, J = 7.7 Hz, 1H), 7.60
(d, J = 4.0 Hz, 2H), 7.47−7.40 (m, 1H), 6.95−6.89 (m, 2H), 5.51 (s,
G
https://dx.doi.org/10.1021/acs.joc.9b03500
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
1566, 1527, 1460, 1372, 1274, 1020, 907, 868, 765, 691, 591; H
NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8.3 Hz, 2H), 7.78 (d, J =
8.3 Hz, 2H), 4.73 (q, J = 8.3 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 163.3, 132.3, 132.0, 130.4, 122.7 (q, J = 75 Hz), 117.6,
117.2, 61.2 (q, J = 36 Hz). MS (EI) m/z: 229, 210, 180, 160, 130,
102, 75, 51, 38. HRMS (ESI): calcd for C10H7F3NO2 [M + H]+
230.0423; found 230.0425.
13C{1H} NMR (100 MHz, CDCl3): δ = 164.8, 159.9, 134.0, 132.1,
130.3, 130.1, 127.4, 117.9, 116.3, 114.0, 67.3, 55.2. MS (EI) m/z: 267,
224, 192, 164, 130, 121, 91, 51, 39. HRMS (ESI): calcd for
C16H13NNaO3 [M + Na]+ 290.0788; found 290.0786.
4-Chlorobenzyl 4-Cyanobenzoate (4x). White solid (42 mg,
77%); mp 91−93 °C; Rf = 0.59 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3107, 3053, 2961, 2230, 1720, 1595, 1570,
Isopropyl 4-Cyanobenzoate (4p).47 White solid (25 mg, 66%);
1
1491, 1446, 1311, 1116, 1016, 860, 804, 727, 691, 535; H NMR
1
mp 49−51 °C; Rf = 0.71 (petroleum ether/ethyl acetate = 4:1); H
(400 MHz, CDCl3): δ = 8.19−8.11 (m, 2H), 7.77−7.70 (m, 2H),
7.41−7.33 (m, 4H), 5.34 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3):
δ = 164.6, 134.5, 133.7, 133.6, 132.2, 130.1, 129.7, 128.8, 117.8,
116.5, 66.6. MS (EI) m/z: 271, 236, 218, 190, 165, 130, 102, 89, 51,
39. HRMS (ESI): calcd for C15H11ClNO2 [M + H]+ 272.0473; found
272.0466.
NMR (400 MHz, CDCl3): δ = 8.18−8.09 (m, 2H), 7.78−7.69 (m,
2H), 5.27 (hept, J = 6.3 Hz, 1H), 1.38 (d, J = 6.3 Hz, 6H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 164.4, 134.6, 132.1, 130.0, 118.0,
116.1, 69.5, 21.8. MS (EI) m/z: 189, 174, 148, 130, 102, 75, 59, 43.
Cyclohexyl 4-Cyanobenzoate (4q).48 White solid (38 mg, 83%);
1
mp 61−62 °C; Rf = 0.75 (petroleum ether/ethyl acetate = 4:1); H
3-Chlorobenzyl 4-Cyanobenzoate (4y). White solid (34 mg,
63%); mp 86−87 °C; Rf = 0.62 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3066, 2961, 2920, 2227, 1724, 1604, 1576,
NMR (400 MHz, CDCl3): δ = 8.18−8.11 (m, 2H), 7.77−7.70 (m,
2H), 5.08−5.00 (m, 1H), 1.95 (dd, J = 12.0, 5.2 Hz, 2H), 1.79 (dd, J
= 9.6, 3.3 Hz, 2H), 1.59 (ddd, J = 16.0, 10.9, 3.4 Hz, 4H), 1.51−1.39
(m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 164.3, 134.7, 132.1,
130.0, 118.0, 116.0, 74.1, 31.5, 25.3, 23.6. MS (EI) m/z: 229, 200,
188, 148, 130, 102, 82, 67, 55, 41.
1
1481, 1405, 1379, 1176, 1109, 958, 864, 781, 694, 546; H NMR
(400 MHz, CDCl3): δ = 8.19−8.14 (m, 2H), 7.78−7.72 (m, 2H),
7.43 (d, J = 1.0 Hz, 1H), 7.37−7.29 (m, 3H), 5.35 (s, 2H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 164.5, 137.2, 134.5, 133.5, 132.2,
130.1, 129.9, 128.7, 128.3, 126.3, 117.8, 116.5, 66.5. MS (EI) m/z:
271, 236, 218, 190, 165, 130, 102, 89, 51, 39. HRMS (ESI): calcd for
C15H11ClNO2 [M + H]+ 272.0473; found 272.0474.
1,1,1,3,3,3-Hexafluoropropan-2-yl 4-cyanobenzoate (4r). White
solid (36 mg, 60%); mp 62−64 °C; Rf = 0.72 (petroleum ether/ethyl
acetate = 4:1); IR (KBr, cm−1) 3107, 3074, 2982, 2240, 1758, 1613,
1573, 1040, 1017, 908, 866, 762, 725, 695, 546; 1H NMR (400 MHz,
CDCl3): δ = 8.23 (d, J = 8.5 Hz, 2H), 7.83 (d, J = 8.5 Hz, 2H), 6.01
(hept, J = 6.0 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 161.8,
132.6, 130.8, 130.4, 121.6 (m, J = 281 Hz), 117.3, 116.0, 67.3 (m, J =
35 Hz). MS (EI) m/z: 297, 258, 233, 214, 184, 151, 130, 102, 75, 51,
38. HRMS (ESI): calcd for C11H5F6NNaO2 [M + Na]+ 320.0117;
found 320.0115.
Thiophen-2-ylmethyl 4-Cyanobenzoate (4z). Yellow solid (18
mg, 38%); mp 72−74 °C; Rf = 0.61 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3086, 2919, 2849, 2229, 1724, 1609, 1457,
1
1375, 1214, 1105, 979, 848, 764, 712, 543; H NMR (400 MHz,
CDCl3): δ = 8.15 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H), 7.36
(dd, J = 5.1, 1.0 Hz, 1H), 7.19 (d, J = 3.4 Hz, 1H), 7.02 (dd, J = 5.1,
3.5 Hz, 1H), 5.54 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ =
164.6, 137.1, 133.7, 132.2, 130.2, 128.6, 127.2, 126.9, 117.8, 116.5,
61.6. MS (EI) m/z: 243, 207, 191, 162, 130, 102, 97, 53, 45, 39.
HRMS (ESI): calcd for C13H10NO2S [M + H]+ 244.0427; found
244.0413.
Allyl 4-Cyanobenzoate (4s).49 Colorless liquid (31 mg, 83%); Rf =
1
0.67 (petroleum ether/ethyl acetate = 4:1); H NMR (400 MHz,
CDCl3): δ = 8.19−8.13 (m, 2H), 7.78−7.72 (m, 2H), 6.03 (ddt, J =
16.2, 10.5, 5.8 Hz, 1H), 5.42 (dq, J = 17.2, 1.4 Hz, 1H), 5.33 (dd, J =
10.4, 1.2 Hz, 1H), 4.85 (dt, J = 5.8, 1.3 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ = 164.5, 133.9, 132.2, 131.5, 130.1, 119.0, 117.9,
116.4, 66.3. MS (EI) m/z: 187, 148, 130, 102, 75, 51, 39.
Phenethyl 3-Cyanobenzoate (4aa). Yellow liquid (41 mg, 82%);
Rf = 0.62 (petroleum ether/ethyl acetate = 4:1); IR (KBr, cm−1)
3042, 2957, 2903, 2229, 1722, 1605, 1592, 1577, 1490, 1454, 1350,
1274, 1147, 993, 872, 759, 697, 490; 1H NMR (400 MHz, CDCl3): δ
= 8.30−8.26 (m, 1H), 8.25−8.20 (m, 1H), 7.82 (dt, J = 7.7, 1.4 Hz,
1H), 7.57 (td, J = 7.9, 0.4 Hz, 1H), 7.34 (ddd, J = 7.1, 4.4, 1.6 Hz,
2H), 7.30−7.25 (m, 3H), 4.57 (t, J = 7.0 Hz, 2H), 3.10 (t, J = 7.0 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 164.4, 137.3, 135.8,
133.5, 133.1, 131.5, 129.3, 128.8, 128.5, 126.7, 117.8, 112.8, 66.1,
35.0. MS (EI) m/z: 251, 236, 204, 190, 165, 130, 104, 91, 65, 39.
Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C,
76.23; H, 5.29; N, 5.50.
Hex-5-en-1-yl 4-Cyanobenzoate (4t).50 Colorless liquid (39 mg,
86%); Rf = 0.7 (petroleum ether/ethyl acetate = 4:1); 1H NMR (400
MHz, CDCl3): δ = 8.16−8.10 (m, 2H), 7.77−7.71 (m, 2H), 5.80
(ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.06−4.95 (m, 2H), 4.35 (t, J = 6.6
Hz, 2H), 2.17−2.08 (m, 2H), 1.85−1.74 (m, 2H), 1.59−1.48 (m,
2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 164.9, 138.0, 134.1,
132.1, 130.0, 117.9, 116.2, 114.9, 65.6, 33.1, 27.9, 25.1. MS (EI) m/z:
229, 199, 188, 148, 130, 102, 82, 67, 54, 41.
Cyclohex-3-en-1-ylmethyl 4-Cyanobenzoate (4u). Colorless
liquid (36 mg, 75%); Rf = 0.72 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3024, 2921, 2840, 2231, 1724, 1610, 1570,
Methyl 2-Cyanobenzoate (4ab).52 White solid (29 mg, 91%); mp
1
1
50−51 °C; Rf = 0.4 (petroleum ether/ethyl acetate = 4:1); H NMR
1437, 1406, 1274, 1177, 1044, 1019, 961, 861, 767, 657, 545; H
(400 MHz, CDCl3): δ = 8.18−8.09 (m, 1H), 7.84−7.76 (m, 1H),
7.72−7.62 (m, 2H), 3.99 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ = 164.4, 134.7, 132.6, 132.4, 132.2, 131.1, 117.4, 112.8, 52.7. MS
(EI) m/z: 161, 130, 102, 75, 51, 39.
NMR (400 MHz, CDCl3): δ = 8.20−8.09 (m, 2H), 7.80−7.68 (m,
2H), 5.75−5.64 (m, 2H), 4.26 (d, J = 6.5 Hz, 2H), 2.24−2.07 (m,
4H), 1.93−1.81 (m, 2H), 1.48−1.35 (m, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ = 164.9, 134.2, 132.2, 130.0, 127.1, 125.2, 117.9,
116.3, 69.9, 33.0, 28.1, 25.3, 24.3. MS (EI) m/z: 241, 207, 193, 151,
130, 102, 94, 79, 66, 41. Anal. Calcd for C15H15NO2: C, 74.67; H,
6.27; N, 5.81. Found: C, 74.48; H, 6.17; N, 5.88.
Ethyl 2-Cyanobenzoate (4ac).52 White solid (30 mg, 85%); mp
64−66 °C; Rf = 0.56 (petroleum ether/ethyl acetate = 4:1); 1H NMR
(400 MHz, CDCl3): δ = 8.17−8.08 (m, 1H), 7.83−7.75 (m, 1H),
7.70−7.60 (m, 2H), 4.44 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ = 163.9, 134.6, 132.5, 132.5,
132.3, 131.0, 117.4, 112.7, 62.1, 13.9. MS (EI) m/z: 175, 147, 130,
102, 75, 51, 39.
Phenethyl 4-Cyanobenzoate (4v).51 White solid (35 mg, 70%);
1
mp 91−92 °C; Rf = 0.73 (petroleum ether/ethyl acetate = 4:1); H
NMR (400 MHz, CDCl3): δ = 8.15−8.07 (m, 2H), 7.78−7.69 (m,
2H), 7.37−7.30 (m, 2H), 7.30−7.23 (m, 3H), 4.57 (t, J = 7.0 Hz,
2H), 3.09 (t, J = 6.9 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ =
164.8, 137.4, 134.0, 132.1, 130.0, 128.8, 128.6, 126.7, 117.9, 116.3,
66.1, 35.0. MS (EI) m/z: 251, 207, 191, 151, 130, 104, 91, 65, 51, 39.
4-Methoxybenzyl 4-Cyanobenzoate (4w). White solid (36 mg,
68%); mp 69−70 °C; Rf = 0.53 (petroleum ether/ethyl acetate =
4:1); IR (KBr, cm−1) 3068, 2987, 2957, 2834, 2227, 1613, 1589,
Phenethyl 2-Cyanobenzoate (4ad). White solid (44 mg, 87%);
mp 45−46 °C; Rf = 0.46 (petroleum ether/ethyl acetate = 4:1); IR
(KBr, cm−1) 3041, 2957, 2900, 2229, 1720, 1602, 1592, 1575, 1489,
1
1469, 1379, 1302, 1170, 1049, 1007, 800, 724, 574; H NMR (400
MHz, CDCl3): δ = 8.13−8.04 (m, 1H), 7.85−7.77 (m, 1H), 7.70−
7.61 (m, 2H), 7.36−7.28 (m, 4H), 7.25 (ddd, J = 8.6, 5.0, 2.3 Hz,
1H), 4.62 (t, J = 7.2 Hz, 2H), 3.14 (t, J = 7.1 Hz, 2H). 13C{1H} NMR
(100 MHz, CDCl3): δ = 163.8, 137.3, 134.7, 132.6, 132.4, 132.3,
131.0, 128.9, 128.5, 126.6, 117.5, 112.8, 66.5, 34.7. MS (EI) m/z: 251,
1
1517, 1467, 1381, 1246, 1109, 1037, 861, 765, 688, 576; H NMR
(400 MHz, CDCl3): δ = 8.17−8.10 (m, 2H), 7.75−7.69 (m, 2H),
7.42−7.34 (m, 2H), 6.96−6.89 (m, 2H), 5.32 (s, 2H), 3.82 (s, 3H).
H
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J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
232, 204, 190, 165, 130, 104, 91, 65, 39. HRMS (ESI): calcd for
C16H14NO2 [M + H]+ 252.1019; found 252.1019.
Dingsheng Cao − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
Lipeng Long − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
N-(3-Cyano-6-methylpyridin-2-yl)benzamide (5a).15 White solid
(34 mg, 72%); mp 87−89 °C; Rf = 0.27 (petroleum ether/ethyl
acetate = 4:1); 1H NMR (400 MHz, CDCl3) δ = 8.80 (s, 1H), 8.23 (t,
J = 1.5 Hz, 1H), 8.14 (dd, J = 6.8, 1.6 Hz, 2H), 7.87−7.77 (m, 1H),
7.70−7.56 (m, 2H), 6.96 (d, J = 7.5 Hz, 1H), 2.44 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3): δ = 163.4, 157.0, 150.3, 138.9, 135.6,
135.1, 131.1, 129.7, 119.1, 117.7, 113.3, 111.2, 23.8. MS (EI) m/z:
237, 208, 130, 102, 75, 51, 39.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b03500
2,4-Diphenylquinazoline (5b).16 Yellow solid (45 mg, 80%); mp
Notes
1
116−117 °C; Rf = 0.76 (petroleum ether/ethyl acetate = 4:1); H
The authors declare no competing financial interest.
NMR (400 MHz, CDCl3) δ = 8.72 (dd, J = 8.0, 1.6 Hz, 2H), 8.15
(dd, J = 15.9, 8.4 Hz, 2H), 7.89 (ddd, J = 10.9, 8.0, 2.7 Hz, 3H),
7.65−7.58 (m, 3H), 7.58−7.49 (m, 4H). 13C{1H} NMR (100 MHz,
CDCl3): δ = 168.2, 160.1, 151.9, 138.1, 137.6, 133.4, 130.4, 130.1,
129.8, 129.1, 128.6, 128.4, 126.9, 121.6. MS (EI) m/z: 282, 254, 226,
203, 178, 102, 77, 50, 39.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the NSF of Jiangxi
Province (20171ACB21048), the NSF of Jiangxi Provincial
Education Department (GJJ160924, GJJ190754), and the
Innovation Fund of Jiangxi Province (YC2018-S385). We
acknowledge the Analytical & Testing Center of Beijing
Normal University for the high resolution mass spectrometry
detection.
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (5c).17 White solid (36
mg, 81%); mp 110−111 °C; Rf = 0.70 (petroleum ether/ethyl acetate
1
= 4:1); H NMR (400 MHz, CDCl3) δ = 8.34−8.25 (m, 2H), 8.22
(dd, J = 7.9, 1.2 Hz, 1H), 7.80 (ddd, J = 8.2, 7.4, 1.5 Hz, 1H), 7.67
(dd, J = 8.1, 0.5 Hz, 1H), 7.58−7.53 (m, 1H), 7.52−7.46 (m, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ = 159.4, 157.0, 146.8, 136.4,
132.5, 130.1, 128.6, 128.4, 128.2, 128.1, 127.1, 116.9. MS (EI) m/z:
223, 179, 146, 105, 77, 51, 39.
REFERENCES
■
N-(2-Iodophenyl)benzamide (6a).53 White solid (60 mg, 93%);
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1H), 8.02−7.95 (m, 2H), 7.82 (dd, J = 8.0, 1.4 Hz, 1H), 7.63−7.57
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m/z: 323, 196, 105, 77, 51.
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b03500.
1H and 13C NMR spectra (PDF)
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AUTHOR INFORMATION
■
Corresponding Authors
Zhengwang Chen − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China; orcid.org/0000-0002-
6795-9625; Email: chenzwang@126.com
Min Ye − Key Laboratory of Organo-Pharmaceutical Chemistry
of Jiangxi Province, Gannan Normal University, Ganzhou
341000, P. R. China; Email: yemin811@gnnu.cn
Authors
Xiaowei Wen − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
Weiping Zheng − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
Ruolan He − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
Dou Chen − Key Laboratory of Organo-Pharmaceutical
Chemistry of Jiangxi Province, Gannan Normal University,
Ganzhou 341000, P. R. China
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