Pd(OAc)2-catalyzed alkoxylation of arylnitriles via sp 2 C-H bond activation using cyano as the directing group

Article abstract of DOI:10.1021/jo301384r

A Pd(OAc)₂-catalyzed ortho-alkoxylation of arylnitrile was described. Using cyano as a directing group, the aromatic C-H bond can be functionalized efficiently to generate ortho-alkoxylated arylnitrile derivatives with moderate yields. The opti

Full text of DOI:10.1021/jo301384r

Note
pubs.acs.org/joc
Pd(OAc)2‑Catalyzed Alkoxylation of Arylnitriles via sp2 C−H Bond
Activation Using Cyano as the Directing Group
Wu Li† and Peipei Sun*,†,‡,§
†Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing,
210097, China
‡Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science,
Soochow University, Suzhou 215123, China
§Key Laboratory of Applied Photochemistry, Nanjing Normal University, Nanjing, 210097, China
S
* Supporting Information
ABSTRACT: A Pd(OAc)2-catalyzed ortho-alkoxylation of
arylnitrile was described. Using cyano as a directing group,
the aromatic C−H bond can be functionalized efficiently to
generate ortho-alkoxylated arylnitrile derivatives with moderate
yields. The optimal reaction conditions were identified after
examining various factors such as oxidant, solvent, and reaction temperature. The method was compatible to the arylnitriles with
either electron-withdrawing or electron-donating groups.
Scheme 1. Transformation of Aromatic Nitrile
s a highly efficient and atom-economical way to construct
Acarbon−carbon and carbon−heteroatom bonds, transi-
tion-metal-catalyzed C−H activation has received extensive
attention in recent years.1 Directing group assisted activation of
ortho aromatic C−H bonds has met with remarkable success.
The strongly coordinating groups such as acylamino,2a,b
pyridyl,2c oxazolyl,2d and oximido2e used for palladium-
catalyzed C−H bond functionalization have been widely
studied. Utilizing substrates with weakly coordinating directing
groups enables unprecedented breadth in the functionalization
step, owing to the higher reactivity of the putative cyclo-
palladated intermediates, which will be a powerful approach for
developing synthetically versatile reactions.3 Some weakly
coordinating directing groups (e.g., COOH,4a CONHC6F5,4b
OH,4c,d and carbonyl4e) have been used in cyclometalation in
recent years. It is well-known that the cyano group is not only a
coordinating functional group but also an important precursor
for a multitude of transformations into various functional
groups such as carboxylic acids/esters, amide, amines,
aldehydes, tetrazoles, and ketones,5 but the C−H functionaliza-
tion using cyano as a directing group has not received sufficient
attention. Recently, we reported the first example of palladium-
catalyzed cyano group directed C−H functionalization to
synthesize biphenyl-2-carbonitrile derivatives by the reaction of
aryl nitriles with aryl halides.6 A pioneering work of meta-
selective C−H activation based on the weak coordinating
between Pd(II) and cyano group was reported very recently by
Yu.7 We believe expanding the cyano group directed C−H
functionalization should be significant in the synthesis of
nitriles and related compounds on the basis of the coordination
properties and the importance in organic synthesis of this
group.
because of the electronegativity of the elements as well as the
metal−ligand bond strength.8 On the other hand, an immense
number of ether-containing chemicals are produced for the
pharmaceutical, bulk, and fine chemical industries.9 Therefore,
developing novel methodologies for C−O bond formations is
still of interest and a challenging task, and the development of
C−O bond formation reactions has greatly accelerated in
recent years.10 Despite the success of C−H oxygenation
methods, C−H alkoxylation reactions remain scarce. A few
research groups reported the directed ortho-alkoxylation of the
C(sp2)−H bonds of arenes.11 Our ongoing interest in finding
new organic transformations through C−H bond activation
prompted us to explore the utilization of the cyano as a
Transition-metal-catalyzed formation of C−O bond is quite
difficult compared to the formation of C−C or C−N bonds
Received: July 8, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo301384r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
directing group for selective C−H functionalization reaction.
Herein, we describe an efficient method for the synthesis of
alkyl aryl ethers via a Pd-catalyzed, cyano-directed alkoxylation
of C(sp2)−H bonds at the aromatic ring using alcohols as
alkoxylation reagents.
Our investigation started from the reaction of 3,4-
dimethoxybenzonitrile (1a) with anhydrous methanol in the
presence of Pd(OAc)2 and an oxidant. We were delighted to
observe the formation of the desired methoxylated product
2,4,5-trimethoxybenzonitrile (3a). Encouraged by this initial
finding, we commenced a systematic screening to the reaction
conditions to increase the yield of this alkoxylation reaction
(Table 1). Without palladium catalyst, the reaction did not take
efficient oxidant for this reaction (entries 1 and 7−11). Other
oxidants were less effective, and no desired product was
observed when PhI(OAc)2 or Ag2O was employed. The
appropriate amount of Na2S2O8 was 5 equiv. Decreasing the
amount of Na2S2O8 resulted in a reduction of the yield, while
increasing the amount of this oxidant to 6 equiv did not result
in an increase of the yield (entries 12 and 13). Methanol was
used as both reactant and solvent in this reaction. Some
solvents such as dioxane, DCE, CH3CN, DMSO, and NMP to
be used as the cosolvent were tested in order to improve the
yield of the reaction (entries 15−19, respectively). Unfortu-
nately, the presence of these cosolvents did not promote the
reaction, and even inhibited this transformation, and the reason
for this action was not clear. Notably, this ether-forming
reaction required careful temperature regulation (with a gradual
ramp from room temperature to 70 °C). The higher reaction
temperature at the beginning of the reaction led to the
formation of palladium black and lowered the yield (entry 14).
Using the optimized reaction conditions, we then explored
the substrate scope of this cyano-directed alkoxylation reaction.
The results are summarized in Table 2. While methanol and
ethanol were used as alkoxylation reagents, for most of the
arylnitriles we employed, the reaction gave moderate yields. It
seems that dialkoxylation on the two ortho-positions of the
cyano group took place more readily than the monoalkox-
ylation. For example, in entries 2, 3, and 7, only
dimethoxylation products were obtained. In entries 4−6, the
yields of dimethoxylation products were higher than that of
monomethoxylation products. But for the ethoxylation of 4-
methoxybenzonitrile, no diethoxylation product was found
(entry 17). It is worth noting that for the meta-substituted
arylnitriles, the alkoxylation did not occur between cyano and
the meta-substituent because of steric effects (entries 1, 13, 14,
18, 19, 20, and 22). Another interesting result was that the
alkoxylation of 1-naphthonitrile took place on the 8-position
instead of the 2-position (entries 11 and 21). It was maybe
because that the ring strain in the cyclopalladated intermediate
formed with the carbon atom on 8-position was weaker than
that formed with the carbon atom on 2-position. That is to say,
a more stable cyclopalladated intermediate could be generated
on the 8-position.
a
Table 1. Optimization of the Reaction Conditions
b
yield
entry
catalyst
Pd(OAc)2
solvent
methanol
oxidant (equiv)
(%)
1
2
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
K2S2O8 (5.0)
O2
70
c
Pd(OAc)2
Pd(TFA)2
methanol
methanol
38
3
42
4
PdCl2(CH3CN)2 methanol
trace
15
5
Pd(acac)2
PdCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
methanol
methanol
methanol
methanol
methanol
methanol
6
trace
58
7
8
12
9
PhI(OAc)2 (5.0) trace
MeCOOOBut
(5.0)
10
35
11
12
13
14
15
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
methanol
methanol
methanol
methanol
Ag2O (5.0)
0
Na2S2O8 (4.0)
Na2S2O8 (6.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
52
68
42
60
d
methanol/dioxane
(1:1, 3 mL)
16
17
18
19
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
methanol/DCE
(1:1, 3 mL)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
Na2S2O8 (5.0)
57
It also can be seen that the action of the electronic effect of
the substituent on arylnitriles to the reaction was not obvious.
In the presence of an electron-withdrawing group such as nitro,
halogen, or ester or electron-donating group such as methoxyl
and methyl, the reaction could take place normally to give the
desired alkoxylation products. Moreover, the tolerance of the
reaction to these chemically active groups ensures that they can
be further transformed into other different functionalities.
Unfortunately, almost no alkoxylation product was isolated as a
secondary alcohol such as 2-propanol was used under these
reaction conditions (entry 23).
methanol/MeCN
(1:1, 3 mL)
trace
trace
trace
methanol/DMSO
(1:1, 3 mL)
methanol/NMP
(1:1, 3 mL)
a
Unless otherwise specified, all of the reactions were carried out with
1a (1.0 mmol), Pd catalyst (0.1 mmol), and Na2S2O8 (5.0 mmol) in
MeOH (3 mL) at room temperature for 8 h, and then the temperature
b
c
was raised to 70 °C for 16 h. Isolated yields. Pd(OAc)2 (0.05 mmol)
d
was used. The reactions were carried out at 70 °C for 24 h.
The detailed mechanism for this Pd-catalyzed, Na2S2O8-
mediated C−H alkoxylation reaction has not been firmly
established. On the basis of the experimental results and the
related transition-metal-catalyzed C−H activation reactions, a
possible mechanism is proposed to account for the present C−
O bond formation reaction (Scheme 2). First, the coordination
of cyano in arylnitrile to Pd(OAc)2 formed a cyclopalladated
intermediate A in which the cyano group coordinated with
palladium using its π-electrons between carbon and nitrogen. In
fact, the directed C−H functionalization reactions through π-
type coordinating groups recently have been shown to be
place entirely. Pd(OAc)2 was evidently catalytic active to the
reaction, and an appropriate amount of the catalyst was 10 mol
%. Decreasing the amount of Pd(OAc)2 to 5 mol % could result
in a decrease of the yield (entry 2). Other palladium species
such as Pd(TFA)2, PdCl2(CH3CN)2, Pd(acac)2, and
PdCl2(PPh3)2 were substantially less effective (entries 3−6).
It was found that the nature of oxidants played a critical role on
the reaction efficiency. Thus, oxidants such as K2S2O8,
Na2S2O8, PhI(OAc)2, O2, MeCOOOBut, and Ag2O were
examined, and among these, Na2S2O8 proved to be the most
B
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Note
a
Table 2. Pd-Catalyzed Direct Ortho-Alkoxylation of Arylnitrile
a
All of the reactions were carried out using arylnitrile 1 (1.0 mmol), Pd(OAc)2 (0.1 mmol), and Na2S2O8 (5.0 mmol) in MeOH or EtOH (3 mL) at
b
rt for 8 h, and then the temperature was raised to 70 °C for 16 h. Isolated yields.
possible.6,12 Next, acetate presumably participated in aromatic
proton abstraction to generate an aryl palladium intermediate
B, followed by an oxidation of the PdII intermediate B to the
PdIV intermediate C by Na2S2O8 in the presence of
methanol.6,11c,13 Then, a reductive alkoxylation from C
regenerated the PdII catalyst and produces the observed
methoxylated product 3. The dimethoxylated product 4 could
be produced by repeating these processes.
environmentally benign Na2S2O8 was found to be a particularly
effective oxidant in these transformations and exhibited
functional group tolerance. Various aromatic nitriles with either
electron-donating or electron-withdrawing groups could be
alkoxylated directly and efficiently. To the best of our
knowledge, the present work is the first example of transition
metal-catalyzed C−O bond formation using cyano as the
directing group.
In summary, we have developed an efficient method for
direct alkoxylation of arenes via Pd-catalyzed cyano group
directed sp2 C−H bond activation. Inexpensive, safe, and
EXPERIMENTAL SECTION
General Methods. All reactions were run in oven-dried flasks
under nitrogen. Alcohols were dried using general method; other
■
C
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The Journal of Organic Chemistry
Note
132.8, 113.3, 104.7, 56.5. HRMS (ESI): calcd for C9H8ClNO2[H]
198.0322, found 198.0341.
Scheme 2. Proposed Mechanism for the Pd-Catalyzed
Alkoxylation Reaction
4-Bromo-2-methoxybenzonitrile (3f). Yield: 20% (42 mg). Color-
less oil. 1H NMR (CDCl3, 400 MHz): δ 7.42 (d, J = 8.0 Hz, 1H), 7.17
(d, J = 8.0 Hz, 1H), 7.15 (s, 1H), 3.95 (s, 3H). 13C NMR (CDCl3, 100
MHz): δ 161.5, 134.4, 128.9, 124.2, 115.7, 115.3, 100.9, 56.4. HRMS
(ESI): calcd for C8H6BrNO[Na] 233.9530, found 233.9518.
4-Bromo-2,6-dimethoxybenzonitrile (4f). Yield: 58% (140 mg).
1
White solid. Mp: 151−153 °C. H NMR (CDCl3, 400 MHz): δ 6.75
(s, 2H), 3.93 (s, 6H). 13C NMR (CDCl3, 100 MHz): δ 162.7, 129.2,
113.4, 107.7, 90.7, 56.6. HRMS (ESI): calcd for C9H8BrNO2[H]
241.9817, found 241.9825.
Methyl 4-Cyano-3,5-dimethoxybenzoate (4g). Yield: 45% (99
1
mg). White solid. Mp: 125−127 °C. H NMR (CDCl3, 400 MHz): δ
7.64 (s, 2H), 3.97 (s, 3H), 3.96 (s, 3H), 3.91 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 166.2, 166.2, 134.4, 131.4, 121.2, 112.8, 56.2,
52.5. HRMS (ESI): calcd for C11H11NO4[Na] 244.0586, found
244.0609.
5-Methoxylbiphenyl-4-carbonitrile (3h). Yield: 43% (90 mg).
White solid. Mp: 83−85 °C (lit.18 mp 86.5−87.5 °C). 1H NMR
(CDCl3, 400 MHz): δ 7.59−7.65 (m, 3H), 7.45−7.50 (m, 3H), 7.22
(d, J = 6.4 H z, 1H), 7.15 (s, 1H), 4.00 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 161.5, 147.8, 139.6, 134.0, 129.1, 128.8, 127.3, 119.8,
118.0, 110.0, 100.4, 56.1.
reagents were commercially available and were used without
purification. 1H NMR and 13C NMR spectra were recorded in
1
CDCl3 [using (CH3)4Si (for H, δ = 0.00; for 13C, δ = 77.00) as
2-Methoxy-6-nitrobenzonitrile (3i). Yield: 62% (110 mg). White
internal standard]. The following abbreviations were used to explain
the multiplicities: s = singlet, d = doublet, t = triplet, m = multiplet.
Melting points are uncorrected. For the HRMS measurements, Q-
TOF was used.
solid. Mp: 174−176 °C (lit.19 mp 174−177 °C). H NMR (CDCl3,
1
400 MHz): δ 7.86 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1H), 7.34
(d, J = 8.0 Hz, 1H), 4.07 (s, 1H). 13C NMR (CDCl3, 100 MHz): δ
163.0, 134.1, 134.0, 116.9, 116.6, 111.7, 97.4, 57.2.
General Experimental Procedures and Characterizations. A
sealed tube (15 mL) initially fitted with a septum containing
Pd(OAc)2 (0.1 mmol) and Na2S2O8 (5.0 mmol) was evacuated and
purged with nitrogen gas three times. MeOH (3 mL) and arylnitrile
(1.0 mmol) were added to the system, and the reaction mixture was
stirred at rt for 8 h and then stirred at 70 °C for another 16 h. The
mixture was extracted with dichloromethane then washed and dried.
The solution was concentrated by vacuum and separated on a silica gel
column using hexane/EtOAc as eluent to give the corresponding pure
ortho-alkoxylated arylnitrile derivatives.
2-Methoxy-6-methylbenzonitrile (3j). Yield: 47% (69 mg). White
solid. Mp: 61−63 °C (lit.20 mp 61−63 °C). H NMR (CDCl3, 400
1
MHz): δ 7.39 (t, J = 8.0 Hz, 1H), 6.87 (d, J = 8.0 H z, 1H), 6.78 (d, J =
7.6 Hz, 1H), 3.92 (s, 3H), 2.51 (s, 3H). 13C NMR (CDCl3, 100
MHz): δ 161.6, 143.9, 133.5, 122.1, 115.7, 108.2, 102.3, 56.0, 20.5.
8-Methoxy-1-naphthonitrile (3k). Yield: 60% (110 mg). Pale
yellow solid. Mp: 65−67 °C. 1H NMR (CDCl3, 400 MHz): δ 8.00 (d,
J = 8.0 Hz, 1H), 7.91 (d, J = 7.2 Hz, 1H), 7.47−7.53 (m, 3H), 6.97 (m,
1H), 4.07 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 154.8, 135.0,
134.7, 132.9, 127.6, 125.4, 123.9, 121.0, 120.2, 106.9, 106.7, 55.7.
HRMS (ESI): calcd for C12H9NO[Na] 206.0582, found 206.0599.
3-Methoxylbiphenyl-2-carbonitrile (3l). Yield: 52% (108 mg).
2,4,5-Trimethoxybenzonitrile (3a). Yield: 70% (135 mg). Pale
yellow solid. Mp: 102−103 °C (lit.14 mp 105−106 °C). H NMR
1
(CDCl3, 400 MHz): δ 6.97 (s, 1H), 6.51 (s, 1H), 3.95 (s, 3H), 3.92 (s,
3H), 3.85 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 157.6, 154.1,
143.0, 117.0, 114.7, 96.4, 91.5, 56.6, 56.5, 56.2.
1
White solid. Mp: 81−83 °C. H NMR (CDCl3, 400 MHz): δ 7.56−
7.60 (m, 3H), 7.43−7.51 (m, 3H), 7.07 (d, J = 7.8 Hz, 1H), 7.97 (d, J
= 8.0 Hz, 1H), 4.00 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 162.2,
137.3, 138.1, 133.7, 128.8, 128.7, 128.6, 122.0, 116.0, 109.6, 101.0,
56.3. HRMS (ESI): calcd for C14H11NO[Na] 232.0738, found
232.0741.
2,6-Dimethoxybenzonitrile (4b). Yield: 68% (111 mg). White
solid. Mp: 117−118 °C (lit.15 mp 118 °C). H NMR (CDCl3, 400
1
MHz): δ 7.43 (t, J = 8.4 Hz, 1H), 6.55 (d, J = 8.4 Hz, 2H), 3.93 (s,
6H). 13C NMR (CDCl3, 100 MHz): δ 162.6, 134.8, 114.2, 103.4, 91.2,
56.2.
4-Methoxylbiphenyl-3-carbonitrile (3m). Yield: 53% (111 mg).
1
White solid. Mp: 95−97 °C. H NMR (CDCl3, 400 MHz): δ 7.76−
2,6-Dimethoxy-4-methylbenzonitrile (4c). Yield: 60% (106 mg).
White solid. Mp: 138−139 °C (lit.16 mp 138−139 °C). H NMR
1
7.78 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.44−7.48 (m, 2H), 7.36 (m,
1H), 7.05 (d, J = 8.0 Hz, 1H), 3.99 (s, 3H). 13C NMR (CDCl3, 100
MHz): δ 160.6, 138.7, 134.3, 133.0, 132.1, 129.0, 127.7, 126.7, 116.5,
111.7, 102.2, 56.2. HRMS (ESI): calcd for C14H11NO[Na] 232.0738,
found 232.0731.
(CDCl3, 400 MHz): δ 6.37 (s, 2H), 3.90 (s, 6H), 2.40 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 162.4, 146.3, 114.5, 104.4, 88.5, 56.1,
22.9.
2,4-Dimethoxybenzonitrile (3d). Yield: 22% (36 mg). Pale yellow
solid. Mp: 88−89 °C (lit.14 mp 90−91 °C). H NMR (CDCl3, 400
1
4-Methoxy-4′-methylbiphenyl-3-carbonitrile (3n). Yield: 42% (94
1
mg). White solid. Mp: 98−100 °C. H NMR (CDCl3, 400 MHz): δ
MHz): δ 7.45 (d, J = 8.4 Hz, 1H), 6.50 (d, J = 6.8 Hz, 1H), 6.45 (s,
1H), 3.90 (s, 3H), 3,85 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ
164.6, 162.8, 134.9, 117.0, 105.8, 98.9, 93.9, 55.7, 55.5.
7.74−7.77 (m, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H,
7.03 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H), 2.42 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 160.3, 137.6, 135.8, 134.2, 132.7, 131.9, 129.7, 126.5,
116.5, 111.7, 102.2, 56.2, 22.7. HRMS (ESI): calcd for C15H13NO[Na]
246.0895, found 246.0898.
2,4,6-Trimethoxybenzonitrile (4d). Yield: 57% (110 mg). White
solid. Mp: 134−136 °C (lit.14 mp 137−138 °C). H NMR (CDCl3,
1
400 MHz): δ 6.08 (s, 2H), 3.90 (s, 6H), 3.87 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 165.3, 163.8, 114.6, 90.4, 84.2, 56.1, 55.7.
4-Chloro-2-methoxybenzonitrile (3e). Yield: 28% (47 mg). White
2,4-Dichloro-6-methoxybenzonitrile (3o). Yield: 51% (102 mg).
White solid. Mp: 99−100 °C. 1H NMR (CDCl3, 400 MHz): δ 7.12 (s,
1H), 6.90 (s, 1H), 3.97 (s, 1H). 13C NMR (CDCl3, 100 MHz): δ
162.6, 140.5, 138.7, 122.1, 112.9, 110.6, 102.2, 56.9. HRMS (ESI):
calcd for C8H5Cl2NO[Na] 223.9646, found 223.9665.
solid. Mp: 95−97 °C (lit.17 mp 95−97 °C). H NMR (CDCl3, 400
1
MHz): δ 7.49 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 7.00 (s,
1H), 3.95 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ 161.7, 140.7,
134.4, 121.3, 115.7, 112.3, 100.5, 56.4.
2,4,6-Trimethoxybenzonitrile (3p). Yield: 50% (96 mg). White
1
4-Chloro-2,6-dimethoxybenzonitrile (4e). Yield: 42% (83 mg).
solid. Mp: 134−136 °C (lit.14 mp 137−138 °C). H NMR (CDCl3,
1
White solid. Mp: 145−147 °C. H NMR (CDCl3, 400 MHz): δ 6.58
400 MHz): δ 6.08 (s, 2H), 3.90 (s, 6H), 3.87 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 165.3, 163.8, 114.6, 90.4, 84.2, 56.1, 55.7.
(s, 2H), 3.92 (s, 6H). 13C NMR (CDCl3, 100 MHz): δ 162.8, 141.1,
D
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The Journal of Organic Chemistry
Note
2-Ethoxy-4-methoxybenzonitrile (3q). Yield: 48% (85 mg).
Colorless oil. H NMR (CDCl3, 400 MHz): δ 7.47 (d, J = 8.4 Hz,
H.; Shi, W.; Lei, A. W. Chem. Rev. 2011, 111, 1780. (g) Davies, H. L.;
Bois, J. D.; Yu, J. Q. Chem. Soc. Rev. 2011, 40, 1855.
1
1H), 6.50 (d, J = 6.8 Hz, 1H), 6.45 (s, 1H), 4.10 (q, J = 6.8 Hz, 2H),
3.86 (s, 3H), 1.47 (t, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ
164.5, 162.2, 135.0, 117.1, 105.6, 99.2, 94.2, 64.6, 56.7, 14.5. HRMS
(ESI): calcd for C10H11NO2[Na] 200.0687, found 200.0704.
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4-Ethoxybiphenyl-3-carbonitrile (3r). Yield: 54% (120 mg). White
1
solid. Mp: 107−108 °C. H NMR (CDCl3, 400 MHz): δ 7.73−7.78
(m, 2H), 7.51 (t, J = 8.8 Hz, 2H), 7.44 (t, J = 8.0 Hz, 2H), 7.36 (t, J =
8.0 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 4.19 (q, J = 7.2 Hz, 2H), 1.51 (t,
J = 7.2 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ 160.0, 138.7, 134.0,
132.9, 132.1, 129.0, 127.6, 126.6, 116.5, 112.6, 102.5, 64.9, 14.6.
HRMS (ESI): calcd for C15H13NO[Na] 246.0895, found 246.0917.
4-Ethoxy-4′-methoxylbiphenyl-3-carbonitrile (3s). Yield: 47%
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1
(119 mg). White solid. Mp: 103−105 °C. H NMR (CDCl3, 400
MHz): δ 7.67−7.73 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 6.98 (t, J = 8.0
Hz, 3H), 4.17 (q, J = 7.2 Hz, 2H), 3.87 (s, 3H), 1.50 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 100 MHz): δ 159.5, 159.4, 133.8, 132.4,
131.6, 131.3, 127.7, 116.6, 114.4, 112.4, 102.4, 64.9, 55.4, 14.6. HRMS
(ESI): calcd for C16H15NO2[Na] 276.1000, found 276.1003.
4-Ethoxy-3′-methoxylbiphenyl-3-carbonitrile (3t). Yield: 53%
(134 mg). White solid. Mp: 68−70 °C. 1H NMR (CDCl3, 400
MHz): δ 7.71−7.78 (m, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0
Hz, 1H), 7.01 (t, J = 8.0 Hz, 2H), 6.91 (m, 1H), 4.18 (q, J = 8.0 Hz,
2H), 3.88 (s, 3H), 1.51 (t, J = 8.0 Hz, 3H). 13C NMR (CDCl3, 100
MHz): δ 160.1, 160.0, 140.2, 133.9, 132.9, 132.2, 130.1, 119.1, 116.5,
112.9, 112.5, 112.4, 102.4, 64.9, 55.4, 14.6. HRMS (ESI): calcd for
C16H15NO2[H] 254.1181, found 254.1191.
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Ed. 1998, 37, 2180. (b) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am.
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N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970. (d) Giri, R.;
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functionalization reactions, also see: (a) Yoneyama, T.; Crabtree, R.
H. J. Mol. Catal. A: Chem. 1996, 108, 35. (b) Wang, X.; Lu, Y.; Dai, H.
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9880.
8-Ethoxy-1-naphthonitrile (3u). Yield: 56% (110 mg). White solid.
1
Mp: 73−75 °C. H NMR (CDCl3, 400 MHz): δ 7.80 (d, J = 8.0 Hz,
1H), 7.91 (d, J = 8.0 Hz, 1H), 7.46−7.52 (m, 3H), 6.96 (d, J = 8.0 Hz,
1H), 4.28 (q, J = 8.0 Hz, 2H), 1.65 (t, J = 8.0 Hz, 3H). 13C NMR
(CDCl3, 100 MHz): δ 154.1, 135.0, 134.8, 132.9, 127.6, 125.2, 123.7,
120.7, 120.1, 107.4, 107.0, 65.0, 14.3. HRMS (ESI): calcd for
C13H11NO[Na] 220.0738, found 220.0736.
2-Ethoxy-4,5-dimethoxybenzonitrile (3v). Yield: 59% (122 mg).
1
Pale orange solid. Mp: 109−110 °C. H NMR (CDCl3, 400 MHz): δ
6.91 (s, 1H), 6.47 (s, 1H), 4.08 (q, J = 6.8 Hz, 2H), 3.91 (s, 3H), 3.81
(s, 3H), 1.41 (t, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 100 MHz): δ
157.0, 154.0, 143.0, 117.1, 114.5, 97.5, 91.6, 65.4, 56.5, 56.1, 14.7.
HRMS (ESI): calcd for C11H13NO3[Na] 230.0793, found 230.0800.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR and 13C NMR spectra for all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sunpeipei@njnu.edu.cn.
■
Notes
The authors declare no competing financial interest.
(14) Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc. 2012, 134,
2528.
ACKNOWLEDGMENTS
■
(15) Bennetau, B.; Rajarison, F.; Dunoguts, J. Tetrahedron. 1993, 49,
10843.
(16) Robertson, A.; Robinson, R. J. Chem. Soc. 1927, 2196.
(17) Ugi, I.; Fetzer, U.; Eholzer, U.; Knupfer, H.; Offermann, K.
Angew. Chem. 1965, 77, 492.
This work was supported by the National Natural Science
Foundation of China (Project 21272117 and 20972068) and
the Priority Academic Program Development of Jiangsu Higher
Education Institutions.
(18) Bradsher, C. K.; Brown, F. C.; Porter, H. K. J. Am. Chem. Soc.
1954, 76, 2357.
REFERENCES
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