Synthesis of aryl nitriles by palladium-assisted cyanation of aryl iodides using tert-butyl isocyanide as cyano source

Article abstract of DOI:10.1016/j.tet.2015.04.059

Abstract A palladium-catalyzed synthesis of aryl nitriles by the cyanation of aryl iodides with tert-butyl isocyanide as cyano source has been developed. This novel and efficient method avoids the use of toxic cyanides. The reaction is easy-to-handle and shows good functional group compatibility.

Full text of DOI:10.1016/j.tet.2015.04.059

Tetrahedron xxx (2015) 1e5
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Synthesis of aryl nitriles by palladium-assisted cyanation of aryl
iodides using tert-butyl isocyanide as cyano source
,
Xiao Jiang a, Jin-Mei Wang a, Ying Zhang a, Zhong Chen a, Yong-Ming Zhu a
*
,
Shun-Jun Ji b
a College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
b College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A palladium-catalyzed synthesis of aryl nitriles by the cyanation of aryl iodides with tert-butyl isocyanide
as cyano source has been developed. This novel and efficient method avoids the use of toxic cyanides.
The reaction is easy-to-handle and shows good functional group compatibility.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 18 March 2015
Received in revised form 15 April 2015
Accepted 18 April 2015
Available online xxx
Keywords:
Palladium-catalyzed synthesis
Cyanation
tert-Butyl isocyanide
Aryl nitriles
Aryl iodides
1. Introduction
Aryl nitriles are an integral part of many natural products,
pharmaceuticals, agrochemicals, herbicides, pigments, and dyes.1 In
addition, they are easily transformed into other functional groups,
such as amines, acids, amides, aldehydes, and heterocycles.2 As
a result, a number of methods to introduce cyano group to aromatic
ring have been developed. Of these transformations, transition-
metal-catalyzed cyanation of aryl halides2e or aromatic CeH bond
activation was an elegant route to benzonitriles (Scheme 1). How-
ever, typical protocols utilized toxic cyanides (e.g., Cu(CN)2,3
Zn(CN)2,4 NaCN, and KCN5), CH3NO2,6 acetone cyanohydrin,7
cyanogen halides,8 TMSCN,9 N-cyano-N-phenyl-para-toluenesulfo-
namide (NCTS),10 and aryl(cyano)iodonium triflates (DFCT)11 as
cyanating agents. Low toxic CN source was thus highly desired.
K4[Fe(CN)6] was first used by Beller and co-workers to introduce CN
into organic molecules.12 Recently, other CN sources such as am-
monium salts or organic amine/DMSO,13 DMF,14 formamide,14f,g
ethyl cyanoacetate,15a benzyl cyanide,15bed CuSCN,16 NaN3,17 NH3,
and tert-butyl nitrite (TBN)18 have been demonstrated to deliver
nitriles. However, poor functional group tolerance and maneuver-
ability restricted their application.
Scheme 1. Approaches to aryl nitriles.
Isocyanides, which are well known as isoelectronic equivalent of
CO, are powerful C1 building blocks in organic synthesis since the
pioneer work of Passerini and Ugi.19 Palladium-catalyzed iso-
cyanide insertion has been widely applied in the synthesis of
nitrogenous compounds.20 Our group has successfully constructed
CeO, CeC, CeN and aldehydes via metal-catalyzed isocyanide in-
sertion into C-X bonds.21 Nevertheless, the use of isocyanides as
a cyano source has been less explored.22 Palladium-catalyzed
direction CeH cyanation of phenylindole and phenylpyridine was
only reported by Xu and Zhu.22eeg However, those reactions limit
the scope to electron-rich and regioselective nitrogen-containing
indoles or 2-phenylpyridine derivatives. Herein, for further
broadening the application of isocyanides as CN source in the
* Corresponding author. Fax: þ86 512 67166591; e-mail address: zhuyongming@
suda.edu.cn (Y.-M. Zhu).
http://dx.doi.org/10.1016/j.tet.2015.04.059
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
X. Jiang et al. / Tetrahedron xxx (2015) 1e5
synthesis of aromatic and heteroaromatic nitriles, we describe an
efficient palladium-catalyzed cyanation of aryl iodides using tert-
butyl isocyanide as CN source (Scheme 2).
4). Both of 76% yield of the corresponding benzonitrile and 4-
phenylbenzaldehyde were obtained in absence of base, which
might be attributed to the solvent DMF (Table 1, entry 5). Solvent
screening showed that DMSO was better than other non-polar
solvents in the reaction (Table 1, entries 6e8). Lower temperature
led to decrease in the yield of desired product (Table 1, entry 9).
Compared to other palladium catalysts such as PdCl2, Pd(TFA)2, and
Pd2(dba)3, Pd(OAc)2 gave better result (Table 1, entries 10e12). The
absence of Pd(OAc)2 decreased the yield of the product (Table 1,
entry 13), and trace amounts of the desired product was produced
without Cu(TFA)2$xH2O (Table 1, entry 14). With using CF3COOAg
as oxidant, only 23% yield was got (Table 1, entry 15). Different
Cu(II) oxidants were tested (Table 1, entries 16e20). And we ob-
served that the presence of H2O promoted this reaction (Table 1,
entries 16, 19, and 20e22). When the reaction was run with 10% of
Cu(TFA)2$xH2O under O2, no desired product was detected (Table 1,
entry 23). However, attempt to utilize other isocyanides such as
cyclohexyl isocyanide was not successful (Table 1, entry 24). Thus,
the optimized reaction conditions was aryl halide (1 equiv), tert-
Scheme 2. Cyanation using isocyanide as CN source.
butyl isocyanide (3 equiv), Pd(OAc)2 (5 mol %), and Cu(TFA)2$xH2O
(2 equiv) in DMSO at 130 C under N2 atmosphere.
ꢀ
2. Results and discussion
Next we explored the scope and limitation of the new protocol
(Scheme 3). Only 27% yield of nitrile was obtained when using 4-
bromobiphenyl (Scheme 3, 1b). Both electron neutral (Scheme 3,
1be5b, 15b, 16b, 17b, 19b, and 20b) and electron deficient (Scheme
3, 6be14b, and 18b) aryl iodides were transformed to the desired
aryl nitriles smoothly with 64%e99% yields. Steric hindrance has
a slight effect on the reaction (Scheme 3, 2b and 3b). Various of
Our investigation began with examining the reaction of 4-
phenyliodobenzene and t-BuNC (1.2 equiv) utilizing Pd(OAc)2
(5 mol %) as catalyst, copper(II) trifluoroacetate hydrate (3 equiv) as
oxidant and Na2CO3 (1 equiv) as base at 130 ꢀC. To our delight, 4-
phenylbenzonitrile was produced in 46% yield in DMF under N2
for 12 h (Table 1, entry 1). In the presence of 3 equiv of t-BuNC,
completed conversion was achieved under 2 equiv of Cu(T-
FA)2$xH2O and the yield was increased to 83% (Table 1, entry 2).
Base had no significant effect on this reaction (Table 1, entry 3 and
Table 1
Optimization of reaction conditionsa
1b 98%, 27%c
5b 98%
2b 98%
6b 64%
3b 92%
7b 98%
4b 78%
8b 74%
Entry Catalyst
Oxidant
Additive Solvent Temp (ꢀC) Yieldb (%)
1
2
3
4
5
6
7
8
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 Cu(TFA)2$xH2O
Na2CO3 DMF
Na2CO3 DMF
Cs2CO3 DMF
NaHCO3 DMF
130
130
130
130
130
46c
83
82
84
76
d
DMF
d
DMSO 130
toluene 130
dioxane 120
DMSO 110
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
DMSO 130
98
35
28
59
93
95
92
86
9b 97%
10b 97%
14b 98%
11b 99%
15b 98%
12b 65%
16b 97%
d
d
9
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
PdCl2
Cu(TFA)2$xH2O
d
13b 80%
Pd(TFA)2 Cu(TFA)2$xH2O
Pd2(dba)3 Cu(TFA)2$xH2O
d
d
d
Cu(TFA)2$xH2O
d
d
Pd(OAc)2
Pd(OAc)2 AgTFA
Pd(OAc)2 CuCl2
Pd(OAc)2 Cu(OAc)2
Pd(OAc)2 Cu(NO3)2$2.5H2O
Pd(OAc)2 CuSO4
Pd(OAc)2 CuSO4$5H2O
Pd(OAc)2 Cu(TFA)2$xH2O
Pd(OAc)2 CuCl2
d
traced
23
45
38
87
59
d
d
17b 98%
18b 66%
19b 94%
20b 99%
d
d
d
d
76
51
52
CaCl2
H2O
d
21b 74%
25b 54%
22b 69%
26b 97%
23b 70%
27b 76%
24b 52%
28b 96%
Pd(OAc)2 Cu(TFA)2$xH2O/O2
Pd(OAc)2 Cu(TFA)2$xH2O
tracee
18f
d
a
Conditions: All reactions were performed with 1a (0.7 mmol), tert-butyl iso-
cyanide (3 equiv), catalyst (5 mol %), oxidant (2 equiv), and additive (1 equiv) in
2.5 mL of solvent under nitrogen for 12 h in a sealed tube unless otherwise noted.
a
Conditions: All reactions were performed with 1 (0.7 mmol), tert-butyl
isocyanide (3 equiv), Pd(OAc)2 (5 mol %), Cu(TFA)2·xH2O (2 equiv) and
b
Isolated yield.
tert-Butyl isocyanide (1.2 equiv), oxidant (3 equiv).
With DPPP (10 mol %).
Performed with 10 mol % of oxidant under O2.
o
c
DMSO (2.5 mL) under nitrogen at 130 C for 4-12 h in a sealed tube unless
d
otherwise noted. b Isolated yield. c 4-Bromobiphenyl.
e
Scheme 3. Synthesis of aryl nitriles.a,b
f
Cyclohexyl isocyanide (3 equiv).
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X. Jiang et al. / Tetrahedron xxx (2015) 1e5
3
functional groups including ether, halogen, nitryl, ketone, ester and
pyrrolyl are well tolerated, affording the desired products with
good to excellent yields (Scheme 3, 5be12b). Intriguingly, com-
pounds containing active hydrogen, such as acetamide, amide,
phenol and alcohol, were well tolerated (Scheme 3, 13be15b and
27b). And the product of disubstituted and trisubstituted iodo-
benzenes gave the nitriles in 66%e99% yields (Scheme 3, 17be20b
and 28b). Notably, moderate to good yields were obtained with
some heteroaromatic substrates (Scheme 3, 21be25b). Besides,
26b was achieved in 97% yield.
solvents used in the reactions were dried and freshly distilled. TLC
was performed on silica HSGF254 plates. Melting points were de-
termined with a digital melting-point apparatus. 1H and 13C NMR
spectra were obtained from a solution in CDCl3 or DMSO-d6 with
TMS as internal standard using a 400/101 or 151 MHz (1H/13C)
spectrometer.
4.2. General procedure for the synthesis of aryl nitriles
1be28b
When the reaction was performed with N-tert-butylbiphenyl-4-
carboxamide20d under the standard reaction conditions, no desired
1b was observed, which indicated nitrile can not be converted from
amide in this reaction conditions. As shown in Table 1, entries 13, 14
and 15, both of Pd(OAc)2 and Cu(TFA)2 can catalyze this trans-
formation. Based on the reports of Xu and Zhu,22eeg we preliminarily
speculate the following possible mechanism (Scheme 4). Electro-
philic palladation of Pd(II) with 1a leads to the intermediate A. The
key imidoyl Pd intermediate B is generated via migratory insertion of
isocyanide.Thentheproductof1bwasobtainedwiththeelimination
of Isobutene from B. And palladium(II) species can be regenerated by
the oxidation of Cu(II). In absence of Pd, Cu(I) carboxylate-isonitrile
complex can also provide tert-butyl isocyanide for migratory in-
sertion.22 And with the formation of Cu(I) carboxylate-isonitrile,23
product 1b can be achieved through intermediate C and D followed
by reductive elimination of Cu(I) in the absence of palladium.
Aryl iodide (0.7 mmol, 1 equiv), tert-butyl isocyanide (2.1 mmol,
237
mL, 3 equiv), Pd(OAc)2 (0.035 mmol, 8 mg, 5 mol %), Cu(T-
FA)2$xH2O (1.4 mmol, 405 mg, 2 equiv) and DMSO (2.5 mL) were
added to a 15 mL sealed tube, and stirred at 130 ꢀC for 4e12 h under
nitrogen. After completion of the reaction indicated by TLC, the
mixture was extracted with Et2O (5ꢁ10 mL). The combined organic
phases was dried over Na2SO4, and concentrated under vacuum.
Then the residue was purified by column chromatography on silica
gel using petroleum ether (30e60 ꢀC)/Et2O as eluant to provide the
pure target product.
4.2.1. Biphenyl-4-carbonitrile (1b).18d 1b was obtained as a white
solid (123 mg, 98%) following the general procedure for 12 h. Mp.
86e87 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.68 (q, J¼8.3 Hz, 4H),
7.61e7.56 (m, 2H), 7.49 (t, J¼7.3 Hz, 2H), 7.44 (dd, J¼8.3, 6.1 Hz, 1H).
13C NMR (101 MHz, CDCl3)
127.2, 118.9, 110.8.
d 145.5, 139.0, 132.5, 129.1, 128.6, 127.6,
4.2.2. 4-Methylbenzonitrile (2b).18d 2b was obtained as a colorless
oil (80 mg, 98%) following the general procedure for 4 h. 1H NMR
(400 MHz, CDCl3)
d
7.49 (d, J¼8.1 Hz, 2H), 7.24 (d, J¼7.9 Hz, 2H), 2.39
(s, 3H). 13C NMR (101 MHz, CDCl3)
21.8.
d 143.7, 132.0, 129.8, 119.1, 109.2,
4.2.3. 2-Methylbenzonitrile (3b).18d 3b was obtained as a colorless
oil (75 mg, 92%) following the general procedure for 5 h. 1H NMR
(400 MHz, CDCl3)
d
7.60 (d, J¼7.7 Hz, 1H), 7.49 (t, J¼7.6 Hz, 1H),
7.38e7.24 (m, 2H), 2.56 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 142.0,
132.7, 132.6, 130.3, 126.3, 118.3, 112.8, 20.6.
4.2.4. 4-tert-Butylbenzonitrile (4b).24a 4b was obtained as a color-
less oil (87 mg, 78%) following the general procedure for 8 h. 1H
NMR (400 MHz, CDCl3)
d
7.57 (d, J¼8.6 Hz, 2H), 7.47 (d, J¼8.5 Hz,
2H), 1.32 (s, 9H). 13C NMR (101 MHz, CDCl3)
119.2, 109.3, 35.3, 31.0.
d 156.7, 132.0, 126.2,
4.2.5. 4-Methoxybenzonitrile (5b).18d 5b was obtained as a white
Scheme 4. Plausible mechanism.
solid (91 mg, 98%) following the general procedure for 6 h. Mp.
62e63 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.56 (d, J¼9.0 Hz, 2H), 6.93
3. Conclusion
(d, J¼8.9 Hz, 2H), 3.84 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 162.9,
In summary, we have developed a novel and efficient protocol
for palladium-catalyzed cyanation of aryl iodides using tert-butyl
isocyanide as cyano source. This method features a new mode of
application of isocyanide insertion. And it provides a convenient
cyanation approach with wide scope of both aromatic and heter-
oaromatic compounds in good to excellent yields, even for aro-
matics having activated hydrogen and electron-withdrawing
substituents. Further investigation into detailed mechanisms and
synthetic applications are underway.
134.09, 119.3, 114.8, 103.9, 55.6.
4.2.6. 4-Fuorobenzonitrile (6b).18d 6b was obtained as a colorless oil
(54 mg, 64%) following the general procedure for 5 h. 1H NMR
(400 MHz, CDCl3)
NMR (101 MHz, CDCl3)
118.2, 117.0 (d, J¼22.7 Hz), 108.7 (d, J¼3.7 Hz).
d
7.73e7.61 (m, 2H), 7.18 (t, J¼8.6 Hz, 2H). 13C
d
165.2 (d, J¼256.6 Hz), 134.8 (d, J¼9.4 Hz),
4.2.7. 4-Chlorobenzonitrile (7b).18d 7b was obtained as a white solid
(94 mg, 98%) following the general procedure for 6 h. Mp. 92e93 ꢀC.
4. Experimental section
4.1. General
1H NMR (400 MHz, CDCl3)
d
7.59 (d, J¼8.6 Hz, 2H), 7.45 (d, J¼8.6 Hz,
2H). 13C NMR (101 MHz, CDCl3)
d
139.6, 133.4, 129.7, 118.0, 110.8.
4.2.8. 4-(Trifluoromethyl)benzonitrile (8b).24b 8b was obtained as
Chemicals and reagents were purchased from commercial
suppliers and used without special instructions. All anhydrous
a colorless oil (88 mg, 74%) following the general procedure for 8 h.
1H NMR (400 MHz, CDCl3)
d
7.81 (d, J¼8.2 Hz, 2H), 7.76 (d, J¼8.2 Hz,
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4
X. Jiang et al. / Tetrahedron xxx (2015) 1e5
2H). 13C NMR (101 MHz, CDCl3)
(q, J¼3.7 Hz), 123.2 (q, J¼273.0 Hz), 117.6, 116.18 (d, J¼1.2 Hz).
d
134.7 (q, J¼33.4 Hz), 132.8, 126.32
procedure for 6 h. Mp. 105e106 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.16e7.01 (m, 2H), 6.88 (d, J¼8.9 Hz, 1H), 4.35e4.13 (m, 4H). 13
C
NMR (101 MHz, CDCl3)
64.6, 64.1.
d 147.8,143.8,125.9,121.2,118.9,118.3,104.4,
4.2.9. 4-Nitrobenzonitrile (9b).18d 9b was obtained as a white solid
(100 mg, 97%) following the general procedure for 6 h. Mp.
147e148 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.35 (d, J¼8.3 Hz, 2H), 7.89
4.2.20. 3,4,5-Trimethoxybenzonitrile (20b).24a 20b was obtained as
(d, J¼8.3 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d
150.1, 133.6, 124.3,
a white solid (134 mg, 99%) following the general procedure for 6 h.
118.4, 116.9.
Mp. 95e96 ꢀC. 1H NMR (400 MHz, CDCl3)
d
6.81 (s, 2H), 3.84 (s, 3H),
3.82 (s, 6H). 13C NMR (101 MHz, CDCl3)
106.6, 61.0, 56.3.
d 153.5, 142.2, 118.9, 109.4,
4.2.10. 4-Acetylbenzonitrile (10b).18d 10b was obtained as a white
solid (98 mg, 97%) following the general procedure for 6 h. Mp.
52e54 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.04 (d, J¼8.2 Hz, 2H), 7.77
4.2.21. Thiophene-2-carbonitrile (21b).5e 21b was obtained as
(d, J¼8.2 Hz, 2H), 2.64 (s, 3H). 13C NMR (101 MHz, CDCl3)
d
196.7,
a yellow oil (56 mg, 74%) following the general procedure for 8 h. 1H
140.0, 132.6, 128.8, 118.0, 116.5, 26.9.
NMR (400 MHz, CDCl3)
d
7.62 (ddd, J¼6.2, 4.4, 1.1 Hz, 2H), 7.13 (dd,
J¼5.0, 3.8 Hz, 1H). 13C NMR (151 MHz, CDCl3)
d 137.4, 132.6, 127.6,
4.2.11. Methyl 4-cyanobenzoate (11b).18d 11b was obtained as
114.2, 109.9.
a white solid (112 mg, 99%) following the general procedure for 6 h.
Mp. 65e67 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.08 (d, J¼8.1 Hz, 2H),
4.2.22. Isonicotinonitrile (22b).12c 22b was obtained as a yellow
7.69 (d, J¼8.6 Hz, 2H), 3.90 (s, 3H). 13C NMR (101 MHz, CDCl3)
solid (50 mg, 69%) following the general procedure for 6 h. Mp.
d
165.3, 133.9, 132.2, 130.0, 117.9, 116.3, 52.7.
79e81 ꢀC. 1H NMR (400 MHz, CDCl3)
d
8.78 (d, J¼3.5 Hz, 2H), 7.51
(d, J¼4.0 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d 150.8, 125.3, 120.4,
4.2.12. 4-(1H-Pyrrol-1-yl)benzonitrile (12b).5b 12b was obtained as
116.4.
a white solid (76 mg, 65%) following the general procedure for 5 h.
Mp. 101e103 ꢀC. 1H NMR (400 MHz, CDCl3)
d
7.71 (d, J¼7.9 Hz, 2H),
4.2.23. Nicotinonitrile (23b).7a 23b was obtained as a yellow oil
7.47 (d, J¼8.2 Hz, 2H), 7.14 (s, 2H), 6.41 (s, 2H). 13C NMR (101 MHz,
(51 mg, 70%) following the general procedure for 8 h. 1H NMR
CDCl3)
d
143.7, 133.8, 119.9, 118.9, 118.6, 112.2, 108.6.
(400 MHz, CDCl3)
d
8.85 (s, 1H), 8.78 (d, J¼4.9 Hz, 1H), 7.94 (d,
J¼8.0 Hz,1H), 7.41 (dd, J¼6.9, 5.9 Hz,1H). 13C NMR (101 MHz, CDCl3)
4.2.13. N-(4-Cyanophenyl)acetamide (13b).13b 13b was obtained as
d 153.0, 152.4, 139.3, 123.7, 116.5, 110.1.
a white solid (90 mg, 80%) following the general procedure for 7 h.
Mp. 205e206 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d
10.37 (s, 1H), 7.74
169.2, 143.5,
4.2.24. 1H-Indole-5-carbonitrile (24b).5b 24b was obtained as
(s, 4H), 2.08 (s, 3H). 13C NMR (101 MHz, DMSO-d6)
d
a white solid (52 mg, 52%) following the general procedure for 6 h.
133.3, 119.1, 118.9, 104.7, 24.2.
Mp. 107e108 ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.86 (s, 1H), 7.99 (s,
1H), 7.48 (d, J¼8.5 Hz, 1H), 7.41 (dd, J¼8.5, 1.3 Hz, 1H), 7.37e7.33 (m,
4.2.14. 4-Cyanobenzamide (14b).18e 14b was obtained as a white
1H), 6.63 (s, 1H). 13C NMR (101 MHz, CDCl3)
126.5, 124.8, 121.1, 112.2, 103.4, 102.6.
d 137.7, 127.7, 126.7,
solid (100 mg, 98%) following the general procedure for 10 h. Mp.
222e224 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d 7.29 (s, 1H), 7.07 (d,
J¼8.3 Hz, 2H), 6.97 (d, J¼8.2 Hz, 2H), 6.75 (s, 1H). 13C NMR
4.2.25. 1-Methyl-1H-indole-5-carbonitrile (25b).15a 25b was ob-
(101 MHz, DMSO-d6)
d
166.6, 138.3, 132.4, 128.3, 118.4, 113.8.
tained as a white solid (59 mg, 54%) following the general pro-
cedure for 6 h. Mp. 69e70 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.96 (s,
4.2.15. 4-Hydroxybenzonitrile (15b).5e 15b was obtained as a white
1H), 7.44 (dd, J¼8.5, 1.3 Hz, 1H), 7.36 (d, J¼8.5 Hz, 1H), 7.17 (d,
solid (82 mg, 98%) following the general procedure for 6 h. Mp.
J¼3.1 Hz, 1H), 6.56 (d, J¼3.1 Hz, 1H). 13C NMR (151 MHz, CDCl3)
112e113 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d
10.6 (s, 1H), 7.61 (d,
d 138.3, 131.2, 128.3, 126.6, 124.6, 121.0, 110.2, 102.5, 102.3, 33.2.
J¼6.7 Hz, 2H), 6.89 (d, J¼6.1 Hz, 2H). 13C NMR (101 MHz, DMSO-d6)
d
161.7, 134.3, 119.6, 116.5, 101.1.
4.2.26. Methyl 5-cyanobenzo[b]thiophene-2-carboxylate
(26b).24c 26b was obtained as a white solid (147 mg, 97%) follow-
ing the general procedure for 12 h. Mp. 161e162 ꢀC. 1H NMR
4.2.16. 1-Naphthonitrile (16b).18d 16b was obtained as a yellow oil
(104 mg, 97%) following the general procedure for 6 h. 1H NMR
(400 MHz, CDCl3)
d
8.19 (s, 1H), 8.07 (s, 1H), 7.95 (d, J¼7.8 Hz, 1H),
(400 MHz, CDCl3)
(t, J¼7.3 Hz, 2H), 7.62 (t, J¼7.6 Hz, 1H), 7.55 (t, J¼7.5 Hz, 1H),
7.48e7.40 (m, 1H). 13C NMR (101 MHz, CDCl3)
133.3, 132.9, 132.7,
d
8.16 (d, J¼8.3 Hz,1H), 8.00 (d, J¼8.3 Hz,1H), 7.84
7.64 (d, J¼8.4 Hz,1H), 3.96 (s, 3H).13C NMR (101 MHz, CDCl3)
d 162.4,
145.8, 138.5, 136.3, 130.2, 129.9, 128.5, 124.0, 118.8, 109.0, 53.0.
d
132.4, 128.7, 128.6, 127.6, 125.1, 125.0, 117.9, 110.2.
4.2.27. 4-(Hydroxymethyl)benzonitrile (27b).15e 27b was obtained
as a yellow oil (71 mg, 76%) following the general procedure for 6 h.
4.2.17. 3,5-Dimethylbenzonitrile (17b).18d 17b was obtained as a yel-
1H NMR (400 MHz, CDCl3)
d
7.56 (d, J¼8.1 Hz, 2H), 7.42 (d, J¼8.0 Hz,
low solid (90 mg, 98%) following the general procedure for 6 h. Mp.
2H), 4.70 (s, 1H), 3.28 (s, 1H). 13C NMR (101 MHz, CDCl3)
132.2, 127.0, 118.9, 110.6, 63.8.
d 146.6,
44e45 ꢀC.1H NMR (400 MHz, CDCl3)
d
7.14 (s, 2H), 7.12 (s,1H), 2.24 (s,
1H). 13C NMR (101 MHz, CDCl3)
d 139.0,134.6,129.6,119.2,111.9, 21.0.
4.2.28. 3,5-Dihydroxybenzonitrile (28b).24f 28b was obtained as
4.2.18. 3,5-Difluorobenzonitrile (18b).24d 18b was obtained as a yel-
a white solid (91 mg, 96%) following the general procedure for 6 h.
low oil (64 mg, 66%) following the general procedure for 8 h. 1H
Mp. 154e156 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d 10.05 (s, 2H), 6.56
NMR (400 MHz, CDCl3)
d
7.24e7.19 (m, 2H), 7.10 (tt, J¼8.6, 2.3 Hz,
(d, J¼2.2 Hz, 2H), 6.53 (t, J¼2.2 Hz, 1H). 13C NMR (101 MHz, DMSO-
1H). 13C NMR (101 MHz, CDCl3)
d
163.0 (dd, J¼253.3, 12.6 Hz), 116.6
d6) d 159.3, 119.1, 112.3, 109.9, 107.9.
(t, J¼3.7 Hz), 115.98e115.54 (m), 114.74 (t, J¼11.5 Hz), 109.57
(t, J¼24.9 Hz).
Acknowledgements
4.2.19. 2,3-Dihydrobenzo[b][1,4]dioxine-6-carbonitrile (19b).24e 19b
We gratefully acknowledge the financial support by PAPD (A
was obtained as a white solid (106 mg, 94%) following the general
Project Funded by the Priority Academic Program Development of
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X. Jiang et al. / Tetrahedron xxx (2015) 1e5
5
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Science Foundation of China, No. 21172162).
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