Copper-catalyzed aerobic oxidative synthesis of aryl nitriles from benzylic alcohols and aqueous ammonia

Article abstract of DOI:10.1039/c3ob00002h

Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH₃(aq.) as the nitrogen source, O₂ as the oxidant and TEMPO as the co-catalyst. Furthermore, copper-catalyzed one-pot synthesis of primary aryl amides from alcohols was also achieved.

Full text of DOI:10.1039/c3ob00002h

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Copper-catalyzed aerobic oxidative synthesis of aryl
nitriles from benzylic alcohols and aqueous ammonia†
Cite this: DOI: 10.1039/c3ob00002h
Chuanzhou Tao,* Feng Liu, Youmin Zhu, Weiwei Liu and Zhiling Cao
Received 2nd January 2013,
Accepted 20th March 2013
Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH3(aq.) as the
nitrogen source, O2 as the oxidant and TEMPO as the co-catalyst. Furthermore, copper-catalyzed one-pot
synthesis of primary aryl amides from alcohols was also achieved.
DOI: 10.1039/c3ob00002h
www.rsc.org/obc
Introduction
Aryl nitriles are versatile building blocks in the synthesis of
natural products, pharmaceuticals, agricultural chemicals and
dyes.1 Development of newer methods for the synthesis of aryl
nitriles is of significant interest. General synthetic methods
include Sandmeyer’s reaction,2 transition metal-catalyzed
cross-coupling of aryl halides or direct C–H functionalization
of arenes.3 However, inorganic cyanide salts, generally toxic,
were used and the reactions produce large amounts of inor-
ganic salts as waste. Environmentally benign approaches are
considerably attractive, and many excellent examples have
been reported. For instance, metal-catalyzed dehydration of
aryl oximes or amides,4 changing the CN source to DMF via
the C–H functionalization of arenes,5 and especially, oxidative
dehydrogenation of benzylic alcohols,6 azides7 or methyl
arenes8 have been extensively investigated.
As alcohols are inexpensive and easily available, it would be
advantageous to synthesize nitriles directly from alcohols. Oxi-
dative reaction of alcohols and ammonia to produce nitriles
has been studied using reagents such as I2/DIH,6a I2/TBHP,6b
NiSO4/K2S2O8/NaOH,6c MnO2/MgSO4,6d and (Bu4N)2S2O8/Cu-
(HCO2)2/Ni(HCO2)2/KOH6e (Scheme 1). However, one drawback
has been that stoichiometric amounts of reactive oxidants
were needed, not to mention their high cost and the gener-
ation of environmentally hazardous/toxic byproducts.
Obviously, molecular oxygen as an oxidant has remarkable
advantages, including its abundance, low cost, and benign
byproducts (usually only H2O). The development of catalytic
aerobic oxidation methodologies would be highly desirable.9
Scheme 1 Ammoxidation of alcohols to nitriles.
Recently, Mizuno et al. reported a highly efficient Ru(OH)x/
Al2O3-catalyzed aerobic synthesis of aryl nitriles from alcohols
and the hydration of nitriles to yield primary amides
(Scheme 1).10 The reaction represents a major advance in the
nitrile synthesis, but is carried out at 120–130 °C in an auto-
clave in many cases.
Aerobic oxidation of alcohols to aldehydes catalyzed by
copper has been well studied,11 and the catalyst Cu2+/TEMPO/
Bipy/KOBut was usually used to synthesize aldehydes with
oxygen as an oxidant. Meanwhile, in Mizuno’s work,10b Schiff-
bases were regarded as intermediates which would oxidatively
dehydrogenate to produce nitriles. If ammonia, as a nitrogen
source, is introduced into the reaction of copper-catalyzed
aerobic oxidative synthesis of aldehydes, it would probably
condense with aldehydes to produce Schiff-bases which would
subsequently be converted into nitriles catalyzed by copper.
This hypothesis prompted us to examine copper-catalyzed syn-
thesis of aryl nitriles directly from benzylic alcohols. To the
best of our knowledge, employing copper as a catalyst in
aerobic oxidative synthesis of nitriles has not been disclosed.
Herein, we demonstrate a copper-catalyzed aerobic catalytic
system for the synthesis of aryl nitriles from benzylic alcohols
(Scheme 1). This catalyst system expands the toolbox for syn-
thesis of nitriles through transition metal-catalyzed aerobic
oxidation of alcohols. Moreover, it is a highly desirable
method not only because copper is cheap, readily available
and environmentally benign, but also because of the mild
reaction conditions to give a high conversion.
School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang
222005, P. R. of China. E-mail: chuanzhoutao@yahoo.com.cn;
Fax: +86 (518)85895401; Tel: +86 (518)85895401
†Electronic supplementary information (ESI)
available. See DOI:
10.1039/c3ob00002h
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reaction (87–97%, entries 6–9). Furthermore, the method
could be applied to the transformation of allylic alcohols to
Results and discussion
Our study began with an examination of the conversion of unsaturated nitriles. Cinnamyl nitrile could be quantitatively
benzyl alcohols to benzonitriles with Sheldon’s catalyst obtained from cinnamyl alcohol without isomerization, hydro-
(CuCl2/TEMPO/Bipy/KOBut),11 and aqueous ammonia was genation, and hydration of the double bonds (entry 10).
added as a nitrogen source (Table 1). Delightfully, the desired Heteroatom-containing alcohols also reacted smoothly to
product was obtained in excellent yield (94%) at 80 °C afford the corresponding nitriles in high yields (83–89%,
(entry 1). We speculated that aqueous ammonia could act both entries 11, 12). However, aliphatic primary alcohols could not
as a ligand and a base, replacing the 2,2′-bipyridine and KOBut be converted under the standard conditions (entries 13, 14).
in the reaction. Thus, phenyl nitrile was obtained in good yield
During the reaction, aldehydes were supposed to form
(77–78%; entries 2, 3), indicating that KOBut was not necessary initially11 and subsequently converted into nitriles. Thus, we
for the transformation. Using CuCl2 as a catalyst under ligand- evaluated the Cu(NO3)2/NH3(aq.)/O2 system in the direct trans-
free and base-free conditions, different solvents were examined formation of aryl aldehydes into nitriles (Table 3). With the
(entries 4–7). It was found that good yields of the desired pro- standard conditions, electron-rich aryl aldehydes could be
ducts were obtained in DMSO (entry 4) and DMF (entry 7), smoothly converted into the desired products with high iso-
lower yields were obtained in dioxane and H2O. Copper and lated yields (84–89%, entries 1–3, 6). The transformation of
TEMPO are critical for the conversion, and no products were aryl aldehydes containing weak electron-withdrawing groups
detected in the absence of CuCl2 or TEMPO (entries 8, 9). could also be realized (entry 4). However, aryl aldehydes carry-
Next, we screened the copper sources with different valences. ing strong electron-withdrawing groups gave poor results. For
Gratifyingly, CuBr2, Cu(NO3)2, and Cu(OAc)2 all gave excellent example, the isolated yield is only 5% for 4-nitrobenzaldehyde
yields (entries 10–12) and the yield was up to 98% with Cu- (entry 5). It is noteworthy that the yield from Cu(NO3)2-cata-
(NO3)2. However, no products were obtained with CuSO4 or lyzed oxidation of 4-nitrobenzylalcohol (Table 2, entry 5, 92%)
CuO (entries 13, 14). Additionally, cuprous salts also exhibited is much higher than 4-nitrobenzaldehyde (5%). Similarly, cin-
high activity and good yields were obtained (entries 15, 16).
namyl and 3-pyridyl aldehyde were found to be poor substrates
The above results show that Cu(NO3)2/TEMPO/NH3(aq.)/O2 (entries 7, 8). Electron-rich heteroaryl aldehydes gave satisfac-
is an efficient combination for the synthesis of aryl nitriles tory results. For instance, 60% isolated yield was obtained for
directly from benzyl alcohols. Using the optimized conditions, thiophene-3-aldehyde (entry 9). Also, aliphatic aldehydes could
we next explored the scope and generality of the process not be obtained from aliphatic primary alcohols with the stan-
(Table 2). It was found that benzylic alcohols carrying electron- dard conditions (entry 10).
donating and electron-withdrawing groups could be smoothly
Very recently, Lu et al. reported copper-catalyzed hydration
converted into the desired products with excellent isolated of nitriles with the aid of acetaldoxime in which coordination
yields (91–95%, entries 1–5). Benzylic alcohols carrying an of copper salts to nitriles results in an enhanced electrophili-
ortho-substituent were also found to readily participate in the city of the nitrile carbon to hydroxy in acetaldoxime.12 Then
Table 1 Copper-catalyzed transformation of benzyl alcohol (1a) to benzonitrile (2a)a
Entry
Cat. (5 mol%)
Co-cat. (5 mol%)
Ligand (5 mol%)
Base (5 mol%)
NH3
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
—
CuBr2
Cu(NO3)2
Cu(OAc)2
CuSO4
CuO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
—
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
2,2′-Bipyridine
KOBut
KOBut
—
—
—
—
—
—
—
—
—
—
—
—
—
—
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
NH3(aq.)
CH3CN
CH3CN
CH3CN
DMSO
DMF
Dioxane
H2O
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
94
77
78
80
79
5
35
0
0
96
98(62c)
92
0
<1
86
94
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
9
10
11
12
13
14
15
16
CuCl
CuBr
a Reaction conditions: benzyl alcohol (1 mmol), catalyst (5 mol%), TEMPO (5 mol%), 25% NH3(aq.) (3 mmol), solvent (1 mL), O2 (1 atm.), 5 h,
80 °C. b GC yield. c At 50 °C, 10 h.
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Table 2 Copper-catalyzed synthesis of aryl nitriles (2) from benzylic alcohols
(1)a
Table 3 Copper-catalyzed synthesis of aryl nitriles (2) from aryl aldehydes (3)a
Entry
1
3
2
Yieldb (%)
85
Entry
1
1
2
Yieldb (%)
92
2
3
84
86
2
3
93
95
4
5
84
5
4
5
91
92
6
89
6
7
97
87
7
8
9
16
11
60
8
9
95c
93c
10
CH3(CH2)10–CHO 3j
CH3(CH2)10–CN 2n
0c
a Reaction conditions: aldehyde (3 mmol), Cu(NO3)2 (5 mol%), 25%
NH3(aq.) (9 mmol), DMSO (3 mL), O2 (1 atm.), 5 h, 80 °C. b Isolated
yield. c Reaction time is 20 h.
10
11
12
98
89
83
transformation from benzylic alcohol to nitrile, acetaldoxime
and H2O were introduced into the reaction. As shown in
Table 4, the practical utility of this one-pot procedure has been
demonstrated by synthesizing a number of primary aryl
amides with good to excellent yields (65–97%).
13
14
0d
0d
Conclusions
CH3(CH2)10–CH2OH 1n
CH3(CH2)10–CN 2n
To sum up, in the present study we report a new and efficient
method for the synthesis of aryl nitriles directly from the corre-
sponding benzylic alcohols. It was found that benzylic alcohols
could be easily converted into aryl nitriles by using aqueous
ammonia (25%) as a nitrogen source, Cu(NO3)2–TEMPO as the
catalyst and O2 as the oxidant. Furthermore, one-pot synthesis
of primary aryl amides could also be achieved. The present
procedure is simple, efficient and environmentally benign,
a Reaction conditions: alcohol (3 mmol), Cu(NO3)2 (5 mol%), TEMPO
(5 mol%), 25% NH3(aq.) (9 mmol), DMSO (3 mL), O2 (1 atm.), 5 h,
80 °C. b Isolated yield. c Reaction time is 7 h. d Reaction time is 20 h.
we explored the one-pot method for the synthesis of primary
aryl amides directly from benzylic alcohols. After the
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1.0 mmol of benzyl alcohol (1a) and 1 mL of solvent were
added. The vessel was flushed with O2 and 3.0 mmol of NH3
(aq., 25–28%) was added. The vessel was sealed and the reac-
tion mixture was stirred in an oil bath at 80 °C for 5 hours.
After cooling to room temperature, the mixture was diluted
with 20 mL CH2Cl2. 1.0 mmol of bromobenzene was added as
an internal standard. The product was yielded by GC.
Note: In order to supply enough O2, a 100 mL reaction vessel
was used.
Table 4 Copper-catalyzed one-pot synthesis of aryl amides (4) from benzylic
alcohols (1)a
Entry
1
1
4
Yieldb (%)
94
Copper-catalyzed synthesis of aryl nitriles (2) from benzylic
alcohols (1): general procedure
2
3
4
97
70
85
To a 250 mL round-bottomed flask equipped with a magnetic
stirrer, 0.15 mmol of Cu(NO3)2, 0.15 mmol of TEMPO,
3.0 mmol of benzylic alcohol (1) and 3 mL of DMSO were
added. The vessel was flushed with O2 and 9.0 mmol of NH3
(aq., 25–28%) was added. The vessel was sealed and the reac-
tion mixture was stirred in an oil bath at 80 °C for 5 hours.
After cooling to room temperature, the mixture was partitioned
between ethyl acetate and brine. The organic layer was separ-
ated, and the aqueous layer was extracted with ethyl acetate
twice. The combined organic layers were dried over MgSO4,
and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, EtOAc-PE) to afford the
product (2). The products obtained herein are all known com-
pounds, and 1H NMR and 13C NMR are presented below.
Note: In order to supply enough O2, a 250 mL reaction vessel
was used.
5
6
7
92
89
65
a Reaction conditions: (1) alcohol (3 mmol), Cu(NO3)2 (5 mol%),
TEMPO (5 mol%), 25% NH3(aq.) (9 mmol), DMSO (3 mL), O2 (1 atm.),
5 h, 80 °C. (2) Acetaldoxime (6 mmol), H2O (15 mL), 100 °C, 24 h.
b Isolated yield.
Copper-catalyzed synthesis of aryl nitriles (2) from aryl
aldehydes (3): general procedure
To a 250 mL round-bottomed flask equipped with a magnetic
stirrer, 0.15 mmol of Cu(NO3)2, 3.0 mmol of aryl aldehyde (3)
and 3 mL of DMSO were added. The vessel was flushed with
O2 and 9.0 mmol of NH3 (aq., 25–28%) was added. The vessel
was sealed and the reaction mixture was stirred in an oil bath
at 80 °C for 5 hours. After cooling to room temperature, the
mixture was partitioned between ethyl acetate and brine. The
organic layer was separated, and the aqueous layer was
extracted with ethyl acetate twice. The combined organic layers
were dried over MgSO4, and concentrated in vacuo. The residue
was purified by column chromatography (silica gel, EtOAc–PE)
to afford the product (2). The products obtained herein are all
allowing for a practical route to aryl nitriles and amides. The
convenience of aqueous ammonia and the low cost of the cata-
lytic copper system give this method potential to production
on an industrial scale.
Experimental
General experimental: all chemicals were obtained from a
commercial source and used without further purification.
Flash column chromatography was performed on silica
1
known compounds, and H NMR and 13C NMR are presented
below.
Note: In order to supply enough O2, a 250 mL reaction vessel
was used.
1
230–400 mesh. H-NMR, 13C-NMR spectra were recorded on a
Bruker Advance 400 spectrometer at ambient temperature in
CDCl3. Chemical shifts are reported in ppm relative to TMS.
Melting points were measured on a SGW X-4 microscope, and
are uncorrected.
Benzonitrile (2a).13 Liquid. 1H NMR (300 MHz, CDCl3) δ
7.67–7.54 (m, 3H), 7.45 (t, J = 7.7 Hz, 2H). 13C NMR (75 MHz,
CDCl3) δ 132.5, 131.7, 128.8, 118.5, 112.0.
4-Methylbenzonitrile (2b).14 M.P.: 21–22 °C. 1H NMR
(500 MHz, CDCl3) δ 7.48 (d, J = 8.1 Hz, 2H), 7.23 (t, J = 7.1 Hz,
2H), 2.38 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 143.5, 131.8,
129.7, 118.9, 109.1, 21.6.
Optimization of reaction conditions: copper-catalyzed
transformation of benzyl alcohol (1a) to benzonitrile (2a)
To a 100 mL round-bottomed flask equipped with a magnetic
4-Methoxybenzonitrile (2c).14 M.P.: 63–64 °C. 1H NMR
stirrer, 0.05 mmol of the catalyst, 0.05 mmol of TEMPO, (300 MHz, CDCl3) δ 7.60–7.53 (m, 2H), 6.99–6.91 (m, 2H), 3.85
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(s, 3H). 13C NMR (75 MHz, CDCl3) δ 162.8, 133.8, 119.1, 114.7, in vacuo. The residue was purified by column chromatography
103.8, 55.4.
(silica gel, EtOAc–PE) to afford the product (4). The products
1
4-Chlorobenzonitrile (2d).14 M.P.: 90–91 °C. 1H NMR obtained herein are all known compounds, and H NMR and
(300 MHz, CDCl3) δ 7.53 (dd, J = 8.7, 2.1 Hz, 2H), 7.43–7.36 (m, 13C NMR are presented below.
2H). 13C NMR (75 MHz, CDCl3) δ 138.5, 132.3, 128.6, 116.9,
109.8.
Note: In order to supply enough O2, a 250 mL reaction vessel
was used.
Benzamide (4a).18 M.P.: 128–129 °C. 1H NMR (300 MHz,
4-Nitrobenzonitrile (2e).14 M.P.: 116–117 °C. 1H NMR
(300 MHz, CDCl3) δ 8.40–8.32 (m, 2H), 7.95–7.87 (m, 2H). 13C CDCl3) δ 7.87–7.78 (m, 2H), 7.56–7.47 (m, 1H), 7.42 (ddt, J =
NMR (75 MHz, CDCl3) δ 133.5, 124.3, 118.4, 116.8.
8.3, 6.7, 1.4 Hz, 2H), 6.45 (s, br, 2H). 13C NMR (75 MHz,
1-Naphthonitrile (2f).15 M.P.: 28–29 °C. H NMR (500 MHz, CDCl3) δ 170.0, 133.7, 131.9, 128.6, 127.5.
1
CDCl3) δ 8.18 (d, J = 8.2 Hz, 1H), 8.01 (d, J = 8.3 Hz, 1H),
4-Methoxybenzamide (4b).18 M.P.: 164–165 °C. 1H NMR
7.90–7.82 (m, 2H), 7.63 (ddd, J = 8.3, 7.0, 1.2 Hz, 1H), (300 MHz, CDCl3) δ 7.78 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 8.9 Hz,
7.60–7.54 (m, 1H), 7.45 (dd, J = 8.3, 7.2 Hz, 1H). 13C NMR 2H), 5.90 (s, br, 2H), 3.85 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
(125 MHz, CDCl3) δ 133.2, 132.8, 132.5, 132.2, 128.6, 128.5, 169.1, 162.8, 130.9, 129.4, 114.0, 55.6.
127.5, 125.0, 124.8, 117.7, 110.1.
2-(Benzyloxy)benzamide (4c).19 M.P.: 115–116 °C. 1H NMR
2-(Benzyloxy)benzonitrile (2g).15 M.P.: 69–70 °C. 1H NMR (300 MHz, CDCl3) δ 8.24 (dd, J = 7.8, 1.8 Hz, 1H), 7.73 (s, br,
(300 MHz, CDCl3) δ 7.59–7.24 (m, 7H), 7.05–6.88 (m, 2H), 5.14 1H), 7.50–7.33 (m, 6H), 7.07 (ddd, J = 8.3, 6.9, 3.0 Hz, 2H), 6.38
(s, 2H). 13C NMR (75 MHz, CDCl3) δ 160.2, 135.6, 134.3, 133.7, (s, br, 1H), 5.17 (s, 2H). 13C NMR (75 MHz, CDCl3) δ 167.2,
128.6, 128.1, 126.9, 121.0, 116.4, 112.9, 102.3, 70.5.
157.2, 135.6, 133.3, 132.6, 129.0, 128.7, 127.9, 121.5, 121.3,
2-Chlorobenzonitrile (2h).16 M.P.: 42–43 °C. 1H NMR 112.8, 71.3.
(300 MHz, CDCl3) δ 7.67 (dd, J = 7.7, 1.6 Hz, 1H), 7.61–7.48 (m,
2-Nitrobenzamide (4d).18 M.P.: 169–170 °C. 1H NMR
2H), 7.39 (td, J = 7.4, 1.6 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ (300 MHz, CDCl3) δ 8.10–8.00 (m, 1H), 7.73–7.55 (m, 3H), 5.84
136.7, 134.0, 133.9, 130.5, 127.2, 115.9, 113.3.
2-Nitrobenzonitrile (2i).13 M.P.: 55–56 °C. 1H NMR 129.0, 128.8, 124.7.
(500 MHz, CDCl3) δ 8.41–8.33 (m, 1H), 7.97 (dt, J = 7.6, 3.8 Hz,
Cinnamamide (4e).18 M.P.: 134–135 °C. H NMR (500 MHz,
1H), 7.95–7.87 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 148.5, CDCl3) δ 7.63 (d, J = 15.7 Hz, 1H), 7.54–7.49 (m, 2H), 7.37 (dd,
(s, br, 2H). 13C NMR (75 MHz, CDCl3) δ 133.6, 131.0, 130.9,
1
135.6, 134.5, 133.9, 125.5, 115.0, 107.8.
J = 10.1, 5.7 Hz, 3H), 6.48 (d, J = 15.7 Hz, 1H), 5.90 (s, br, 2H).
1
Cinnamonitrile (2j).14 Liquid. H NMR (300 MHz, CDCl3) δ 13C NMR (125 MHz, CDCl3) δ 168.1, 142.4, 131.0, 130.0, 128.9,
7.50–7.19 (m, 6H), 5.84 (d, J = 16.7 Hz, 1H). 13C NMR (75 MHz, 128.0, 119.8.
CDCl3) δ 150.3, 133.4, 131.0, 128.9, 127.2, 118.0, 96.2.
1
Nicotinamide (4f).10b M.P.: 129–130 °C. H NMR (300 MHz,
Nicotinonitrile (2k).17 M.P.: 48–49 °C. 1H NMR (300 MHz, CDCl3) δ 9.04 (s, 1H), 8.76 (s, 1H), 8.17 (d, J = 5.8 Hz, 1H),
CDCl3) δ 8.96–8.89 (m, 1H), 8.85 (dd, J = 5.0, 1.6 Hz, 1H), 8.01 7.81–7.32 (m, 1H), 6.21 (s, 2H). 13C NMR (75 MHz, CDCl3) δ
(dt, J = 8.0, 1.9 Hz, 1H), 7.48 (ddd, J = 7.9, 5.0, 0.8 Hz, 1H). 13C 152.8, 148.4, 135.6, 131.0, 128.9, 123.7.
NMR (75 MHz, CDCl3) δ 152.9, 152.3, 139.2, 123.6, 116.4,
110.0.
Furan-2-carboxamide (4g).18 M.P.: 84–85 °C. 1H NMR
(300 MHz, CDCl3) δ 7.48–7.43 (m, 1H), 7.14 (d, J = 3.5 Hz, 1H),
Thiophene-3-carbonitrile (2l).14 Liquid. H NMR (500 MHz, 6.50 (dd, J = 3.4, 1.7 Hz, 1H), 6.37 (s, br, 2H). 13C NMR
CDCl3) δ 7.93 (s, 1H), 7.42 (s, 1H), 7.29 (d, J = 4.1 Hz, 1H). (75 MHz, CDCl3) δ 160.5, 147.7, 144.4, 115.0, 112.2.
13C NMR (125 MHz, CDCl3) δ 133.5, 126.2, 125.3, 112.5, 108.6.
1
Copper-catalyzed synthesis of primary aryl amides (4) from
benzylic alcohols (1): general procedure
Acknowledgements
To a 250 mL round-bottomed flask equipped with a magnetic We are grateful to China Postdoctoral Science Foundation
stirrer, 0.15 mmol of Cu(NO3)2, 0.15 mmol of TEMPO, (20110491383), the Project of Natural Science Foundation of
3.0 mmol of benzylic alcohol (1) and 3 mL of DMSO were Jiangsu Education Committee (10KJB150001), the Scientific
added. The vessel was flushed with O2 and 9.0 mmol of NH3 and Technological Research Project of Lianyungang (CG1004),
(aq., 25–28%) was added. The vessel was sealed and the reac- the Open-end Funds of Jiangsu Key Laboratory of Marine
tion mixture was stirred in an oil bath at 80 °C for 5 hours. Biotechnology (2009HS02), and the Open-end Funds of
The reaction mixture was cooled to room temperature and the Jiangsu Marine Resources R & D Institute (JSIMR10C05).
seal was removed. The vessel was flushed with N2 and 6 mmol
of acetaldoxime was added to the solution followed by addition
of 15 mL of H2O. The vessel was sealed and the reaction
mixture was stirred in an oil bath at 110 °C for 24 hours. After
Notes and references
cooling to room temperature, the mixture was quenched with
ethyl acetate. The organic layer was separated, and the
aqueous layer was extracted with ethyl acetate twice. The com-
bined organic layers were dried over MgSO4, and concentrated
1 (a) A. J. Fatiadi, in Preparation and Synthetic Applications
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