The Journal of Organic Chemistry
Note
2
6
dd = double of doublet, dt = double of triplet, and td = triple of doublet.
Coupling constants (J) were reported in hertz unit (Hz).
4-(Trifluoromethyl)benzonitrile (Table 2, entry 8). EA/hexane =
1
1:5, 87% (74.3 mg); H NMR (400 MHz, CDCl ) δ 7.82 (d, J = 8.4 Hz,
3
2H), 7.77 (d, J = 8.3 Hz, 2H); 13C{ H} NMR (101 MHz, CDCl
1
)
Procedure for Optimization of Nitroxyl/NO -Catalyzed
3
x
Aerobic Oxidative Conversion of Aldehydes to Nitriles
δ 134.5 (q, J = 33.4 Hz), 132.7, 126.2 (q, J = 3.7 Hz), 123.0 (q, J =
2
3
1
(
Table 1). A 15 mm flame-dried test tube, which was equipped with
273.0 Hz), 117.4, 116.0.
8c
a magnetic stir bar and charged with nitroxyl radical (5 mol %,
4-Nitrobenzonitrile (Table 2, entry 9). EA/hexane = 1:5, 91%
1
0
.025 mmol), NH X (2.4 equiv, 1.2 mmol), and NaNO (10 mol %,
(67.3 mg); H NMR (400 MHz, CDCl ) δ 8.37 (d, J = 8.8 Hz, 2H), 7.91
4
2
3
(d, J = 8.8 Hz, 2H); 13C{ H} NMR (101 MHz, CDCl ) δ 150.0, 133.5,
1
0.05 mmol, 3.5 mg), was evacuated and backfilled with oxygen (this
3
process was repeated 3 times). After 0.5 mL of solvent was added,
124.3, 118.3, 116.8.
27
4
0
-methylbenzaldehyde (0.5 mmol, 59.0 μL), HNO3 (20 mol %,
.1 mmol, 6.4 μL), and solvent (0.5 mL) were added in sequence. The
2,4,6-Trimethylbenzonitrile (Table 2, entry 10). EA/hexane = 1:5,
1
56% (40.7 mg); H NMR (400 MHz, CDCl ) δ 6.93 (s, 2H), 2.48
3
1
3
1
solution was stirred at 70 °C under an O balloon. After the indicated
(s, 6H), 2.32 (s, 3H); C{ H} NMR (101 MHz, CDCl
128.2, 117.6, 110.3, 21.6, 20.6.
Isophthalonitrile (Table 2, entry 11). Crude H NMR (400 MHz,
) δ 142.8, 141.9,
3
2
time, the reaction was cooled to room temperature and diluted by
adding EtOAc and water. Two layers were separated, and the aqueous
2
6
1
CDCl ) δ 7.98 (s, 1H), 7.93 (d, J = 8.0 Hz, 2H), 7.68 (t, J = 7.9 Hz, 1H).
layer was extracted with EtOAc. The combined organic layers were dried
3
8b
1
Piperonitrile (Table 2, entry 12). EA/hexane = 1:5, 88% (64.6 mg);
H NMR (400 MHz, CDCl ) δ 7.21 (d, J = 8.1 Hz, 1H), 7.03 (s, 1H),
over MgSO , filtered, and concentrated in vacuo. The H NMR yield of
4
1
the desired product was determined by integration using an internal
standard (1,1,2,2-tetrachloroethane).
3
13
1
6.87 (d, J = 8.1 Hz, 1H), 6.07 (s, 2H); C{ H} NMR (101 MHz,
CDCl ) δ 151.5, 148.0, 128.2, 118.9, 111.4, 109.1, 104.9, 102.2.
General Procedure for Aerobic Oxidative Conversion of
3
8
b
Aldehydes to Nitriles Catalyzed by 4-AcNH-TEMPO/NaNO /
1-Naphthonitrile (Table 2, entry 13). EA/hexane = 1:5, 92%
2
1
HNO (Table 2). A 15 mm flame-dried test tube, which was equipped
(70.5 mg); H NMR (400 MHz, CDCl ) δ 8.22 (d, J = 8.3 Hz, 1H), 8.06
3
3
with a magnetic stir bar and charged with aldehyde (0.5 mmol, in case
(d, J = 8.3 Hz, 1H), 7.90 (t, J = 7.4 Hz, 2H), 7.67 (t, J = 7.6 Hz, 1H), 7.60
(t, J = 7.5 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H); 13C{ H} NMR (101 MHz,
1
of solid), 4-AcNH-TEMPO (5 mol %, 0.025 mmol, 5.4 mg), NH OAc
4
(
2.4 equiv, 1.2 mmol, 92.5 mg), and NaNO (10 mol %, 0.05 mmol,
CDCl
117.8, 110.2.
2-Furonitrile (Table 2, entry 14). Crude H NMR (400 MHz,
CDCl ) δ 7.62 (s, 1H), 7.1 (d, J = 3.3 Hz, 1H), 6.56 (d, J = 1.6 Hz, 1H).
3
) δ 133.3, 132.9, 132.6, 132.3, 128.6, 128.6, 127.5, 125.1, 124.9,
2
3
.5 mg), was evacuated and backfilled with oxygen (this process
was repeated 3 times). After 0.5 mL of AcOH was added, aldehyde
0.5 mmol, in case of liquid), HNO (20 mol %, 0.1 mmol, 6.4 μL), and
8c
1
(
3
3
8c
Thiophene-2-carbonitrile (Table 2, entry 15). EA/hexane = 1:5,
AcOH (0.5 mL) were added in sequence. The solution was stirred at
0 °C under an O balloon. After 12 h, the reaction was cooled to room
1
7
7
1
3% (39.6 mg); H NMR (400 MHz, CDCl ) δ 7.65−7.61 (m, 2H),
5
3
2
13
1
.15−7.13 (m, 1H); C{ H} NMR (101 MHz, CDCl ) δ 137.4, 132.5,
temperature and diluted by adding EtOAc and a saturated aqueous
Na CO solution. Two layers were separated, and the aqueous layer was
3
27.6, 114.2, 109.9.
2
3
8c
Cinnamonitrile (Table 2, entry 16). EA/hexane = 1:5, 40% (25.9
extracted with EtOAc. The combined organic layers were concentrated
to a volume of approximately 20 mL by an evaporator. To eliminate the
remaining aldehyde, we added aqueous 1 M sodium metabisulfite
1
mg); H NMR (400 MHz, CDCl ) δ 7.45−7.37 (m, 6H), 5.87 (d, J =
3
1
1
6.7 Hz, 1H); 13C{ H} NMR (101 MHz, CDCl ) δ 150.6, 133.5, 131.2,
3
8c
129.1, 127.4, 118.2, 96.3.
solution (20 mL) to the organic layer and stirred for 2 h. The reaction
mixture was then transferred to a separating funnel, and the aqueous
layer was extracted with EtOAc. The combined organic layers were dried
One-Pot Procedure for the Oxidative Conversion of Alcohol
to Nitrile (Scheme 3). A 15 mm flame-dried test tube, which was
equipped with a magnetic stir bar and charged with 4-bromobenzy-
lalcohol (0.5 mmol, 92.5 mg), 4-AcNH-TEMPO (5 mol %, 0.025 mmol,
over MgSO , filtered, and concentrated in vacuo. The residue was
4
purified by column chromatography to give nitrile products.
5
.4 mg), and NaNO (10 mol %, 0.05 mmol, 3.5 mg) was evacuated and
8
b
2
4
-Methylbenzonitrile (Table 2, entry 1). EA/hexane = 1:5, 90%
backfilled with oxygen (this process was repeated 3 times). After 0.5 mL
of AcOH was added, HNO (20 mol %, 0.1 mmol, 6.4 μL) and AcOH
1
(
(
52.6 mg); H NMR (400 MHz, CDCl ) δ 7.57 (d, J = 8.1 Hz, 2H), 7.30
3
d, J = 7.9 Hz, 2H), 2.45 (s, 3H); 13C{1H} NMR (101 MHz, CDCl ) δ
3
3
(
0.5 mL) were added in sequence. The solution was stirred at 50 °C
1
43.7, 132.0, 129.8, 119.1, 109.3, 21.8.
under an O balloon. After no alcohol spot was observed on TLC
24
2
3
-Methylbenzonitrile (Table 2, entry 2). EA/hexane = 1:5, 92%
(
∼1 h), NH OAc (2.4 equiv, 1.2 mmol, 92.5 mg) in AcOH (1 mL)
4
1
(
53.7 mg); H NMR (400 MHz, CDCl ) δ 7.46 (s, 2H), 7.41 (d, J =
3
solution was added. After an additional 12 h, the reaction was cooled to
room temperature and diluted by adding EtOAc and a saturated aqueous
Na CO solution. Two layers were separated, and the aqueous layer was
13
1
7.4 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 2.39 (s, 3H); C{ H} NMR
(
101 MHz, CDCl ) δ 139.2, 133.6, 132.5, 129.2, 129.0, 119.0, 112.2,
3
2
3
2
1.1.
extracted with EtOAc. The combined organic layers were concentrated
to a volume of approximately 20 mL by evaporator. To eliminate any
remaining aldehyde, we added aqueous 1 M sodium metabisulfite
solution (20 mL) to the organic layer and stirred for 2 h. The reaction
mixture was then transferred to a separating funnel, and the aqueous
layer was extracted with EtOAc. The combined organic layers were dried
2
3
2
-Methylbenzonitrile (Table 2, entry 3). EA/hexane = 1:5, 96%
1
(
(
(
56.1 mg); H NMR (400 MHz, CDCl ) δ 7.59 (d, J = 7.7 Hz, 1H), 7.48
t, J = 7.5 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 7.4 Hz, 1H), 2.55
s, 3H); C{ H} NMR (101 MHz, CDCl ) δ 141.9, 132.6, 132.5, 130.2,
3
13
1
3
1
26.2, 118.1, 112.8, 20.5.
8
c
4
-Methoxybenzonitrile (Table 2, entry 4). EA/hexane = 1:5, 90%
over MgSO , filtered, and concentrated in vacuo. The residue was
4
1
(
(
59.8 mg); H NMR (400 MHz, CDCl ) δ 7.58 (d, J = 9.0 Hz, 2H), 6.95
purified by column chromatography to give 4-bromobenzonitrile in 88%
(80 mg) yield.
3
d, J = 8.9 Hz, 2H), 3.86 (s, 3H); 13C{ H} NMR (101 MHz, CDCl ) δ
1
3
1
62.8, 133.9, 119.2, 114.7, 103.9, 55.5.
25
4
-Hydroxybenzonitrile (Table 2, entry 5). EA/hexane = 1:5, 43%
ASSOCIATED CONTENT
1
■
(
(
25.4 mg); H NMR (400 MHz, CDCl ) δ 7.55 (d, J = 8.6 Hz, 2H), 6.94
3
d, J = 8.6 Hz, 2H); 13C{ H} NMR (101 MHz, CDCl ) δ 160.3, 134.3,
1
S
*
Supporting Information
3
1
19.3, 116.5, 103.0.
8
c
4
-Chlorobenzonitrile (Table 2, entry 6). EA/hexane = 1:5, 94%
1
(
(
64.5 mg); H NMR (400 MHz, CDCl ) δ 7.61 (d, J = 8.6 Hz, 2H), 7.47
3
1
13
d, J = 8.6 Hz, 2H); 13C{ H} NMR (101 MHz, CDCl ) δ 139.5, 133.4,
1
Control experiments and H and C NMR spectra (PDF)
3
1
29.7, 117.9, 110.8.
8
c
4
-Bromobenzonitrile (Table 2, entry 7). EA/hexane = 1:5, 97%
AUTHOR INFORMATION
1
■
(
(
88.2 mg); H NMR (400 MHz, CDCl ) δ 7.63 (d, J = 8.5 Hz, 2H), 7.53
3
d, J = 8.6 Hz, 2H); 13C{ H} NMR (101 MHz, CDCl ) δ 133.4, 132.6,
1
3
128.0, 118.0, 111.2.
D
J. Org. Chem. XXXX, XXX, XXX−XXX