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Organic & Biomolecular Chemistry
Page 8 of 10
ARTICLE
Journal Name
2‐Iodoaniline (2j)33: Yield 98%. White solid. IR (KBr) 3394, (m, 6H), 3.03 (d, J = 6.4 Hz, 2H), 4.82 (s, 1H), 5.09V(isew, 2AHrtic),le7O.n2li9ne‐
1
3290, 3187, 1623, 1474, 1300, 1251, 1146, 1006, 749 cm‐1; H 7.36 (m, 5H).
DOI: 10.1039/C6OB01178K
NMR (400 MHz, CDCl3)
6.74 (d, J = 8.0 Hz, 1H), 7.13 (t, J = 7.2 Hz, 1H), 7.63 (d, J = 8.0 (KBr) 3320, 2932, 2854, 1685, 1541, 1234, 1048, 758, 693
4.08 (s, 2H), 6.47 (t, J = 7.2 Hz, 1H), Benzyl N‐
cyclohexylcabamate (2s)41: Yield 98%. White solid. IR
Hz, 1H).
cm‐1: 1H NMR (270 MHz, CDCl3)
1.05‐1.41 (m, 4H), 1.57‐1.73
2,6‐Dimethoxyaniline (2k)34: Yield 98%. White solid. IR (KBr) (m, 4H), 1.94 (d, J = 5.9 Hz, 2H), 3.50 (t, J = 4.1 Hz, 1H), 4.63 (s,
3464, 3373, 2962, 1603, 1505, 1478, 1144, 766, 597 cm‐1: 1H 1H), 5.08 (s, 2H), 7.29‐7.38 (m, 5H).
NMR (270 MHz, CDCl3) 3.82 (s, 2H), 3.85 (s, 6H), 6.53 (d, J = 1‐Adamantanamine (2t)42: After 2M NaOH was added, the
8.1 Hz, 2H), 6.69 (t, J = 8.1 Hz, 1H).
precipitate was collected by suction filtration. Yield 98 %.
2,3‐Dimethoxyaniline (2l)35: Yield 99%. White solid. IR (KBr) White solid. IR (KBr) 2909, 2851, 1640, 1551, 1457, 1341,
3466, 3369, 2938, 1615, 1322, 1265, 1133, 1089, 733 cm‐1: 1317, 1291 cm‐1; 1H NMR (400 MHz, DMSO‐d6) 1.46‐1.76 (m,
1H NMR (270 MHz, CDCl3) 3.40‐4.10 (br s, 2H), 3.83 (s, 3H), 14H), 1.96 (s, 3H).
3.84 (s, 3H), 6.34 (d, J = 8.1 Hz, 1H), 6.38 (d, J = 8.1 Hz, 1H), Benzyl
N‐(cis‐8‐heptadecenyl)carbamate (2u): Yield 95%.
6.84 (t, J = 8.1 Hz, 1H).
Yellow oil. IR (neat) 3341, 2925, 2854, 1715, 1531, 1456,
3,5‐Dimethylaniline (2m)28: Yield 97%. Brown oil. IR (neat) 1253, 732, 697 cm‐1; 1H NMR (400 MHz, CDCl3) 0.88 (t, J = 6.8
3348, 3019, 1594, 0.005, 1175, 825, 686 cm‐1: H NMR (270 Hz, 3H), 1.27‐1.30 (m, 20H), 1.49‐1.66 (m, 2H), 2.01 (d, J = 6.0
1
MHz, CDCl3) 2.22 (s, 6H), 3.34‐3.69 (br s, 2H), 6.63 (s, 2H), Hz, 2H), 3.16‐3.26 (m, 2H), 4.71 (s, 1H), 5.11 (d, J = 7.2 Hz, 2H),
6.42 (s, 1H).
5.30‐5.39 (m, 2H), 7.29‐7.36 (m, 5H).HRMS (ESI) m/z 410.3041
2‐Aminopyridine (2n)36: Yield 74%. Yellow solid. IR (ATR)
(410.3030 calcd for C25H41NO2Na [M+Na+])
3334, 1600, 1484, 1440, 1321, 1152, 991, 770 cm‐1; H NMR Benzyl N‐[1‐(6‐methoxynaphth‐2‐yl)ethyl]acetamide (2x)
(300 MHz, CDCl3 ) 4.51 (s, 2H), 6.49 (d, J = 8.4 Hz, 1H), 6.63 (t, Yield 65%. [
:
1
25
]
= ‐16.0 (c. = 1.0 in CHCl3). IR (neat) 3287,
D
J = 6.2 Hz, 1H), 7.38‐7.45 (m, 1H), 8.06 (d, J = 5.0 Hz, 1H)
3059, 2950, 1685, 1540, 1318, 1249, 1223, 1058, 1028, 859,
1
2‐Aminoquinoline (2o)37: Yield 76%. Yellow solid. IR (ATR)
698, 471 cm‐1; H NMR (400 MHz, CDCl3) 1.55 (d, J = 6.4 Hz,
3149, 1611, 1506, 1428, 1352, 1123, 1023, 819, 756 cm‐1; H 3H), 3.91 (s, 3H), 4.99‐5.14 (m, 4H), 7.11‐7.15 (m, 2H), 7.34‐
1
NMR (300 MHz, CDCl3 ) 4.84 (s, 2H), 6.72 (d, J = 8.8 Hz, 1H), 7.40 (m, 6H), 7.66‐7.72 (m, 3H). 13C NMR (100 MHz, DMSO‐d6)
7.22‐7.30 (m, 1H), 7.53‐7.68 (m, 3H), 7.88 (d, J = 8.7 Hz, 1H).
22.3, 50.6, 55.2, 66.7, 105.5, 118.9, 124.2, 124.9, 127.2,
128.0, 128.4, 128.5, 128.7, 129.3, 133.9, 136.4, 155.5, 157.6.
LC‐MS (ESI), found [M+Na+] 358.2 (calcd, 358.1). HPLC
General procedure for self‐propagative Lossen rearrangement of
free aliphatic hydroxamic acids to primary amines.
[Chiralpak IC, n‐hexane/2‐propanol = 90 : 10, 0.5 mL/min, =
254 nm, retention times: (minor) 29.9 min, (major) 39.7 min].
A mixture of N‐hydroxy‐2‐phenylacetamide (1p) (0.363 g, 2.4
mmol), K2CO3 (0.332 g, 2.4 mmol), and DMSO (2 mL) were
heated to 90 °C and stirred at the temperature for 2 h. The
mixture was cooled to rt, and then treated with 2M‐HCl (ca. 3
mL) and stirred at the room temperature for 1 h. The reaction
mixture was cooled to 0 °C, and the mixture became the clear
solution. 2 M NaOH (ca. 2 mL) and Z‐chloride (0.51 mL, 3.6
mmol) was added successively. After stirred for 12 h, the
mixture was extracted with Et2O (15 mL × 3). The combined
organic layer was dried over anhydrous Na2SO4, filtered and
evaporated under reduced pressure. The residue was purified
by silica gel column chromatography (hexane/Et2O 1:1) to yield
the pure benzyl N–benzylcarbamate (2p) (0.550 g, 95%) as a
white crystalline solid.
Synthesis
of
1‐(6‐methoxynaphth‐2‐yl)ethylamine
hydrochloride (3).
To a solution of Cbz‐protected amine 2x (20.1 mg, 0.06
mmol) in EtOH (1 mL) was added 10% Pd‐C (0.6 mg). The
flask was charged with hydrogen gas and stirred for 1 h.
The reaction mixture was filtered and removal of the
solvent in vacuo to give
a 1‐(6‐methoxynaphth‐2‐
yl)ethylamine (11.3 mg, 94%) as a pale yellow solid. Then
deprotected amine (11.3 mg) was dissolved in MeOH (0.5
mL) and 2M HCl aq. was added. Standing for 10 min at
room temperature followed by removal of the solvents in
vacuo. The precipitate was collected by suction filtration to
Benzyl N
‐benzylcarbamate (2p)38: Yield 95%. White crystalline
give a 1‐(6‐methoxynaphth‐2‐yl)ethylamine hydrochloride
3
(14.2 mg, 99%) as a white solid.21
solid. IR (KBr)3323, 3032, 1686, 1542, 1454, 1260, 1145, 724,
1
25 = ‐23.0 (c. 0.1 in MeOH). H NMR (270 MHz, D2O)
1
694, cm‐1: H NMR (270 MHz CDCl3) 4.38 (d, J = 6.0 Hz, 2H),
[
]
D
1.59 (d, J = 6.0 Hz), 3.80 (brs, 3H), 4.54 (d, J = 6.0 Hz, 2H),
7.10‐7.21 (m, 2H), 7.39‐7.42 (m, 1H), 7.75‐7.76 (m, 3H).
5.07 (s, 1H), 5.13 (s, 2H), 7.26‐7.35 (m, 10H).
Benzyl
N
‐(2‐phenylethyl)carbamate (2q)39: Yield 82%. White
crystalline solid. IR (KBr)3328, 3030, 1684, 1541, 1454, 1296,
1
1259, 1142, 1030, 746, 697 cm‐1: H NMR (270 MHz, CDCl3)
K2CO3‐mediated reaction of p‐methylbenzohydroxamic
acid in the presence of a catalytic amount of phenyl
isocyanate in DMSO at room temperature
To a solution of p‐methylbenzhydoxamic acid 1a (0.363g,
2.4 mmol) in DMSO (2 mL) were added K2CO3 (0.332 g, 2.4
mmol) and phenyl isocyanate (0.013 mL, 0.12 mmol). The
mixture was stirred for 24 h at room temperature, followed
by 2 M HCl aq. (6 mL) and 2 M NaOH (6 mL) were added.
2.81 (t, J = 6.8 Hz, 2H), 3.46 (t, J = 6.8 Hz, 2H), 4.77 (s, 1H),
5.09 (s, 2H), 7.16‐7.34 (m, 10H).
Benzyl
N
‐(cyclohexylmethyl)carbamate (2r)40: Yield 80%.
Blown solid. IR (KBr) 3303, 2925, 2849, 1697, 1548, 1446,
1
1248, 1138, 730, 694 cm‐1: H NMR (270 MHz, CDCl3) 0.87‐
1.00 (m, 2H), 1.12‐1.29 (m, 2H), 1.43‐1.44 (m, 1H), 1.64‐1.78
8 | J. Name., 2012, 00, 1‐3
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