The Journal of Organic Chemistry
Note
7-Propylquinolin-8-ol (10b). General method with 7-allylquino-
lin-8-ol (185.2 mg, 1.0 mmol), SiliaCat (20.0 mg, 0.1 mol %), and
CPME (2 mL) in chamber B. To chamber A were added zinc granular
(196.2 mg, 3.0 mmol) and 1.7 M HCl (2.33 mL, 4.0 mmol). The
reaction was left at room temperature overnight. The crude reaction
product was filtrated through Celite to give the title compound as a
134.1, 129.3 (2C), 113.7 (2C), 70.7, 69.9, 55.2, 31.9, 31.6, 31.4, 19.4,
13.9. HRMS (ESI-TOF) m/z: [M + H]+ calculated for C14H23O2:
223.1693; found: 223.1692.
2-Amino-4-methoxyphenol (15b). General method with 4-
methoxy-2-nitrophenol (85.3 mg, 0.5 mmol), Pd/C (8.5 mg, 10 wt %),
and methanol (2 mL) in chamber B. To chamber A were added zinc
granular (163.5 mg, 2.5 mmol) and 4 M HCl (1.88 mL, 7.5 mmol).
The reaction was left at room temperature overnight. The crude
reaction product was purified by flash column chromatography (2.5%
ether in pentane) to give the title compound as an off-white solid (67.8
1
brown oil (186.2 mg, 99%). H NMR (400 MHz, CDCl3): δ (ppm)
8.76 (dd, J = 1.5 Hz, J = 4.2 Hz, 1H), 8.48 (br s, 1H), 8.10 (dd, J = 1.6
Hz, J = 8.2 Hz, 1H), 7.45−7.41 (m, 2H), 7.28 (d, J = 8.4 Hz, 1H), 2.94
(t, J = 7.5 Hz, 2H), 1.77 (sext, J = 7.4 Hz, 2H), 1.11 (t, J = 7.3 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ (ppm) 149.2, 147.7, 138.1,
135.9, 129.9, 126.8, 124.4, 120.8, 117.0, 32.0, 23.2, 14.1. HRMS (ESI-
TOF) m/z: [M + H]+ calculated for C12H14NO: 188.1070; found:
188.1071.
1
mg, 97%); mp 135−140 °C. H NMR (400 MHz, CD3SOCD3): δ
(ppm) 8.45 (br s, 1H), 6.54 (d, J = 8.5 Hz, 1H), 6.22 (d, J = 3.0 Hz,
1H), 5.97 (dd, J = 3.0 Hz, J = 8.5 Hz, 1H), 4.53 (br s, 2H). 3.59 (s,
3H). 13C NMR (100 MHz, CD3SOCD3): δ (ppm) 153.5, 138.5, 137.9,
115.0, 101.4, 100.8, 55.3. HRMS (ESI-TOF) m/z: [M + H]+
calculated for C7H10NO2: 140.0706; found: 140.0706.
5-Propylbenzo[d][1,3]dioxole (11b).20 General method with
isosafrole ((E)-5-(prop-1-en-1-yl)benzo[d][1,3]dioxole) (810.9 mg,
5.0 mmol), Pd/C (81.1 mg, 10 wt %), and methanol (10 mL) in
chamber B. To chamber A was added zinc granular (654.0 mg, 10.0
mmol) and 4 M HCl (7.5 mL, 30.0 mmol). The reaction was left at
room temperature overnight. The crude reaction product was filtrated
through Celite and silica to give the title compound as a colorless oil
(812.8 mg, 99%). 1H NMR (400 MHz, CDCl3): δ (ppm) 6.73 (d, J =
7.9 Hz, 1H), 6.69 (d, J = 1.5 Hz, 1H), 6.63 (dd, J = 1.6, J = 7.9 Hz,
1H), 5.92 (s, 2H), 2.52 (t, J = 7.4 Hz, 2H), 1.61 (sext, J = 7.4 Hz, 2H),
0.94 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm)
147.5, 145.4, 136.6, 121.1, 108.9, 108.0, 100.7, 37.8, 24.8, 13.7. HRMS
could not be obtained for this compound. Instead GCMS was
performed. GCMS C10H12O2 [M + e−]; calculated: 164; found: 164
(60%), 135 (100%), 77 (30%).
3-(4-Aminophenyl)propanoic Acid (16b).21 General method
with (E)-3-(4-nitrophenyl)acrylic acid (97.0 mg, 0.5 mmol), Pd/C
(9.7 mg, 10 wt %), and acetic acid (2 mL) in chamber B. To chamber
A were added zinc granular (163.5 mg, 2.5 mmol) and 4 M HCl (1.88
mL, 7.5 mmol). The reaction was left at room temperature overnight.
The crude reaction product was purified by flash column
chromatography (2.5% ether in pentane) to give the title compound
1
as a colorless solid (84.1 mg, 99%); mp 142−144 °C. H NMR (400
MHz, CD3SOCD3): δ (ppm) 6.85 (d, J = 8.2 Hz, 2H), 6.47 (d, J = 8.2
Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 2.41 (t, J = 7.4 Hz, 2H). 13C NMR
(100 MHz, CD3SOCD3): δ (ppm) 174.5, 147.0, 129.0 (2C), 128.4
(2C), 114.4, 36.4, 30.2. HRMS (ESI-TOF) m/z: [M + H]+ calculated
for C9H12NO2: 166.0863; found: 166.0858.
N-(1-(5-Chloropyridin-2-yl)ethyl)acetamide (12b). General
method with N-(1-(5-chloropyridin-2-yl)vinyl)acetamide (196.6 mg,
1.0 mmol), Pd/C (10 mg, 5 wt %), and CPME (2 mL) in chamber B.
To chamber A were added zinc granular (196.2 mg, 3.0 mmol) and 1.7
M HCl (2.33 mL, 4.0 mmol). The reaction was left at room
temperature overnight. The crude reaction product was purified by
flash column chromatography (ethyl acetate) to give the title
compound as a pale brown oil (147.8 mg, 74%). 1H NMR (400
MHz, CDCl3): δ (ppm) 8.41 (d, J = 2.4 Hz, 1H), 7.55 (dd, J = 2.4 Hz,
J = 8.3 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 6.94 (d, J = 5.3 Hz, 1H),
5.06 (pent, J = 7.0 Hz, 1H), 1.95 (s, 3H), 1.37 (d, J = 6.8 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ (ppm) 169.5, 159.4, 147.8, 136.5, 130.5,
122.3, 49.3, 23.3, 22.1. HRMS (ESI-TOF) m/z: [M + H]+ calculated
for C9H12ClN2O: 199.0633; found: 199.0636.
N-(tert-Butyl)-4,5-diphenylpentanamide (13b). General meth-
od with (2E,4Z)-N-(tert-butyl)-4,5-diphenylpenta-2,4-dienamide (76.6
mg, 0.25 mmol), Pd/C (7.6 mg, 10 wt %), and CPME (1 mL) in
chamber B. To chamber A were added zinc granular (49.1 mg, 0.75
mmol) and 4 M HCl (0.56 mL, 2.25 mmol). The reaction was left at
room temperature overnight. The crude reaction product was purified
by flash column chromatography (30% ether in pentane) to give the
title compound as a colorless solid (65.3 mg, 84%); mp 68−70 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 7.29−7.25 (m, 2H), 7.21−7.16
(m, 3H), 7.15−7.10 (m, 3H), 7.03−7.01 (m, 2H), 5.04 (br s, 1H),
2.95−2.89 (m, 2H), 2.86−2.79 (m, 1H), 2.16−2.05 (m, 1H), 1.96−
1.79 (m, 3H), 1.28 (s, 9H). 13C NMR (100 MHz, CDCl3): δ (ppm)
171.9, 144.1, 140.3, 129.1 (2C), 128.4 (2C), 128.1 (2C), 127.8 (2C),
126.3, 125.8, 51.0, 47.5, 44.0, 35.5, 31.1, 28.8 (3C). HRMS (ESI-TOF)
m/z: [M + H]+ calculated for C21H28NO: 310.2165; found: 310.2169.
1-(3-Butoxypropyl)-4-methoxybenzene (14b). General meth-
od with (E)-3-butoxy-1-(4-methoxyphenyl)prop-2-en-1-one (117 mg,
0.5 mmol), Pd/C (11.7 mg, 10 wt %), and n-BuOH (2 mL) in
chamber B. To chamber A were added zinc granular (130.8 mg, 2.0
mmol) and 4 M HCl (1.5 mL, 6.0 mmol). The reaction was left at
room temperature overnight. The crude reaction product was purified
by flash column chromatography (2.5% ether in pentane) to give the
title compound as a colorless oil (86.7 mg, 78%). 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.26−7.10 (m, 2H), 6.86−6.82 (m, 2H), 3.79 (s,
3H), 3.44−3.41 (m, 4H), 2.65 (t, J = 7.4 Hz, 2H), 1.88 (pent, J = 6.5
Hz, 2H), 1.59 (pent, J = 6.6 Hz, 2H), 1.41 (sext, J = 7.1 Hz, 2H), 0.95
(t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm) 157.7,
4-(Ethyl-1,1-d2)-1,1′-biphenyl (2c). General method with 1-
([1,1′-biphenyl]-4-yl)ethan-1-one (196.2 mg, 1.0 mmol), Pd/C (19.6
mg, 10 wt %), and cyclopentyl methyl ether (CPME) (2 mL) in
chamber B. To chamber A were added zinc granular (196.2 mg, 3.0
mmol) and 4 M DCl (2.25 mL, 9 mmol). The reaction was left at 50
°C overnight. The crude product was filtrated through Celite and silica
and concentrated to give the title compound as a colorless oil (182.4
mg, 99%). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.72−7.70 (m, 2H),
7.64 (dt, J = 2.0 Hz, J = 8.3 Hz, 2H), 7.54 (t, J = 7.4 Hz, 2H), 7.44 (dt,
J = 1.1 Hz, J = 6.6 Hz, 1H), 7.39 (dd, J = 1.8 Hz, J = 6.5 Hz, 2H), 2.79
(m, 0.18H), 1.38 (d, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ
(ppm) 143.4, 141.3, 138.7, 128.8 (2C), 128.4 (2C), 127.2 (2C), 127.1
(2C), 127.1, 28.0 (m, C−D), 15.5. HRMS could not be obtained for
this compound. Instead GCMS was performed. GCMS C14H12D2 [M
+ e−]; calculated: 184; found: 184 (70%), 169 (100%), 153 (15%).
2-(Phenylmethyl-d2)benzoic Acid (4c). General method with
potassium 2-benzoylbenzoate (226.2 mg, 1.0 mmol), Pd/C (22.6 mg,
10 wt %), concentrated DCl (0.1 mL), and methanol/CPME (1:1) (2
mL) in chamber B. To chamber A were added zinc granular (196.2
mg, 3.0 mmol) and 4 M DCl (2.5 mL, 9.0 mmol). The reaction was
left at room temperature overnight. The product was obtained by
acidic extraction with 1 M HCl, followed by filtration through Celite
and silica, to give the title compound as a colorless solid (212.1 mg,
1
99%); mp 113−114 °C. H NMR (400 MHz, CDCl3): δ (ppm) 8.15
(d, J = 7.8 Hz, 1H), 7.55 (td, J = 1.0 Hz, J = 7.6 Hz, 1H), 7.42−7.24
(m, 7H), 4.51 (s, 0.17H). 13C NMR (100 MHz, CDCl3): δ (ppm)
173.2, 143.6, 140.8, 133.2, 131.9, 131.9, 129.2 (2C), 128.6, 128.5 (2C),
126.5, 126.2, 39.6−39.1 (m, C−D). HRMS (ESI-TOF) m/z: [M +
H]+ calculated for C14H11D2O2: 215.1036; found: 215.1034.
Ethyl 3-Phenylpropanoate-2,3-d2 (5c). General method ethyl
cinnamate (176.2 mg, 1.0 mmol), Pd/C (17.6 mg, 10 wt %), and
CPME (2 mL) in chamber B. To chamber A were added zinc granular
(130.8 mg, 2.00 mmol) and 4 M DCl (1.5 mL, 6.0 mmol). The
reaction was left at room temperature overnight. The crude reaction
product was filtrated through Celite and silica to give the title
1
compound as a colorless oil (176.6 mg, 98%). H NMR (400 MHz,
CDCl3): δ (ppm) 7.33−7.22 (m, 5H), 4.14 (q, J = 7.1 Hz, 2H), 2.95
(m, 0.75H), 2.61 (m, 1.0H), 1.25 (t, J = 7.2 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ (ppm) 172.9, 140.6, 128.5 (2C), 128.3 (2C), 126.2,
60.4, 35.9−35.3 (m, C−D), 30.9−30.3 (m, C−D), 14.2. HRMS (ESI-
5865
dx.doi.org/10.1021/jo500801t | J. Org. Chem. 2014, 79, 5861−5868