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DOI: 10.1055/s-0029-1219800
Unexpected and Divergent Reactions of N-Formyl-1,2-dihydroquinolines with Sodium Azide: Highly Chemoselective Formation of 2-Substituted Quinolines and Isoxazolo[4,3-c]quinolines
Publication History
Publication Date:
25 March 2010 (online)
Abstract
Efficient and divergent synthesis of 2-substituted quinolines and isoxazolo[4,3-c]quinolines was achieved from N-formyl-1,2-dihydroquinolines with the aid of sodium azide. The synthesis is substituent-dependent. Thus N-formyl-1,2-dihydroquinolines with a hydrogen atom at the 3-position afforded 2-substituted quinolines in good to excellent yields, while with a 3-formyl group, N-formyl-1,2-dihydroquinolines unexpectedly gave isoxazolo[4,3-c]quinolines in high yields.
Key words
azides - quinolines - chemoselectivity - deformylation heterocycles
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References and Notes
Experimental Procedure
for the Synthesis of 4-Chloro-2-substituted Quinolines; 1,3-(2
H
)-dicarbaldehyde
1o-r: To an ice-cold magnetically stirred solution
of DMF (10 mL) and 2-arylquinoline (5.0 mmol), POCl3 (30
mmol, 2.8 mL) was added dropwise. The reaction mixture was heated
to
50 ˚C for 3 h. After which it was poured into
the crush ice, neutralized with sat. K2CO3 solution
and extracted with EtOAc. After drying and condensation of the organic
layer , the crude reaction product was purified by column chromatography
using 5% EtOAc in PE as eluent to afford pure 1o-r.
General Procedure
for the Synthesis of 2-Substituted Quinolines 2a-n:
To a solution of DMSO (5 mL) and 4-chloro-N-formyl-1,2-dihydroquinolines 1a-n (1.0
mmol), NaN3 (1 mmol, 0.065 g) was added at r.t. The solution
was then heated at the indicated temperature (90 ˚C or
120 ˚C or 150 ˚C) for the indicated time. After
completion of the reaction (monitored by TLC) the mixture was treated
with ice-water and extracted with EtOAc. The organic layer was washed
with H2O, and then with brine. After condensation of the
organic layer, the products 2a-n were obtained by column chromatography
(PE-EtOAc).
2-(2-Chloro-6-fluorophenyl)quinoline
(2f)
New compound. Yield: 99%; light yellow
oil; R
f
0.53 (PE-EtOAc,
5:1). ¹H NMR (400 MHz, CDCl3): δ = 8.27
(1 H, d, J = 8.0 Hz), 8.20 (1
H, d, J = 8.4 Hz), 7.89 (1 H,
d, J = 8.0 Hz), 7.74-7.79
(1 H, m), 7.60 (1 H, t, J = 8.0
Hz), 7.50 (1 H, d, J = 8.0 Hz),
7.32-7.38 (2 H, m), 7.11-7.16 (1 H, m). ¹³C NMR
(100 MHz, CDCl3): δ = 160.7 (d, ¹
J
C-F = 248.7
Hz), 152.5, 147.9, 136.4, 134.3, 130.2 (d, ³
J
C-F = 9.9
Hz), 129.8, 129.6, 127.6, 127.3, 127.1, 125.6 (d, 4
J
C-F = 3.1
Hz), 123.0, 114.6 (d, ²
J
C-F = 22.0
Hz). HRMS (ESI): m/z [M + H]+ calcd for
C15H10ClFN: 258.0408; found: 258.0477.
General Procedure
for the Synthesis of 4-Substituted Isoxazolo[4,3-
c
]quinolines-5-(4
H
)-carbaldehyde
3o-r: To a solution of DMSO
(5 mL) and 4-chloro-2-substituted quinolines-1,3 (2H)-dicarbaldehyde 1o-r (1.0
mmol), NaN3 (1.5 mmol, 0.098 g) was added at r.t. and
the reaction mixture was kept at this temperature for 0.5 h. After completion
of the reaction (monitored by TLC) the mixture was treated with
ice-water and extracted with EtOAc. The organic layer was washed
with H2O, and then with brine. After condensation of
the organic layer, the products 3o-r were obtained by column chromatography
(PE-EtOAc).
4-Phenylisoxazolo[4,3-
c
]quinoline-5-(4
H
)-carbaldehyde
(3o)
New compound. Yield: 88%; white crystals;
mp 176-178 ˚C; R
f
0.46
(PE-EtOAc, 3:1). IR (KBr): 3121, 3057, 2851, 1677, 1609,
1574, 1475 cm-¹. ¹H
NMR (400 MHz, DMSO): δ = 9.21 (1 H, s), 8.86 (1
H, s), 7.94 (1 H, d, J = 8.0
Hz), 7.73 (1 H, d, J = 8.0 Hz),
7.54-7.59 (1 H, m), 7.37-7.41 (1 H, m), 7.22-7.30
(3 H, m), 7.16 (2 H, d, J = 8.0
Hz), 7.10 (1 H, s). ¹³C NMR (100 MHz,
DMSO): δ = 162.4, 156.0, 153.8, 138.8, 136.1,
132.2, 128.7, 127.8, 126.3, 126.1, 124.6, 121.2, 117.1, 114.7, 46.9.
HRMS (EI): m/z [M+] calcd
for C17H12N2O2: 276.0899;
found: 276.0899.