Reaction of the Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes with triethyl phosphite: Synthesis of 1-diethylphosphono-1,2-dihydroquinolines and 3-acetoxymethylquinolines

Article abstract of DOI:10.1055/s-2006-942383

A simple synthesis of 1-diethylphosphono-1,2-dihydroquinolines and 3-acetoxymethylquinolines from the reaction of several Morita-Baylis-Hillman acetates of 2-azidobenzaldehydes with triethyl phosphite has been described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942383

PAPER
1953
Reaction of the Morita–Baylis–Hillman Acetates of 2-Azidobenzaldehydes
with Triethyl Phosphite: Synthesis of 1-Diethylphosphono-1,2-dihydro-
quinolines and 3-Acetoxymethylquinolines
S
ynthesis of 1-Die
y
thylphosphon
u
o-1,2-dihyd
n
roquinolines
g
a
nd 3-Aceto
-
xymethy
W
lquinoline
s
oo Yi, Hyun Woo Park, Young Seok Song, Kee-Jung Lee*
Organic Synthesis Laboratory, Department of Chemical Engineering, Hanyang University, Seoul 133791, Korea
Fax +82(2)22984101; E-mail: leekj@hanyang.ac.kr
Received 7 October 2005; revised 24 February 2006
the MBH reaction,16 we have envisioned that 1,2-dihydro-
quinoline derivatives bearing N-diethylphosphoryl group
might in principle be obtained from the MBH acetates
having ortho-iminophosphoranyl group via the construc-
tion of a C–N bond through the intramolecular SN2¢ reac-
tion followed by the MA rearrangement. To the best of
our knowledge, there is no report in the literature for the
synthesis of 1-dialkylphosphono-1,2-dihydroquinolines.
Abstract: A simple synthesis of 1-diethylphosphono-1,2-dihydro-
quinolines and 3-acetoxymethylquinolines from the reaction of sev-
eral Morita–Baylis–Hillman acetates of 2-azidobenzaldehydes with
triethyl phosphite has been described.
Key words: quinoline, triethyl phosphite, Morita–Baylis–Hillman
acetate, Michaelis–Arbuzov rearrangement, iminophosphorane
Accordingly, we first selected methyl 3-acetoxy-3-(2-azi-
dophenyl)-2-methylenepropanoate (4a),16b the MBH
acetate obtained from methyl acrylate and 2-azido-
benzaldehyde, as a substrate for performing three consec-
utive reactions, i.e., the Staudinger reaction,17 the
intramolecular SN2¢ reaction and then MA rearrangement,
with TEP in refluxing toluene. This reaction led to the for-
mation of the desired 3-carbomethoxy-1-diethylphospho-
no-1,2-dihydroquinoline (7a) in 79% yield and 3-
acetoxymethyl-2-methoxyquinoline (9a) in 4% yield. Re-
action of the MBH acetate 4b having an electron-with-
drawing nitro group at the 5-position with TEP afforded
the corresponding 1,2-dihydroquinoline derivatives 7b
(59%) and quinoline 9b (16%). Similar reaction of the
acetate 4c bearing an electron-donating methoxy group at
the 5-position gave exclusively the 1-diethylphosphono-
1,2-dihydroquinoline 7c in excellent yield (91%) within
three hours. When the reactions of the MBH acetates of
methyl vinyl ketone (MVK) 4d–f were run at room tem-
perature, however, the products were found to be the 3-
acetoxymethyl-2-methylquinolines 9d–f (60–72%)18 as
the sole isolated products regardless of aromatic substitu-
ents. In the reaction of the MBH acetates of acrylonitrile
4g–i the expected 3-cyano-1-diethylphosphono-1,2-dihy-
droquinolines 7g–i (57–63%) were obtained (Table 1 and
Scheme 1). Also, an attempt was made to isolate the inter-
mediate iminophosphorane 5b (80%) and transform it into
7b (65%) and 9b (22%) in refluxing toluene for 19 hours.
On changing the MBH acetate 4b to the MBH propanoate
4j, (1,2-dihydroquinolinyl)phosphonate 7b (46%) and
2-methoxy-6-nitro-3-propanoyloxymethylquinoline (9j;
16%) were produced, as expected (Scheme 2).
The quinoline ring system is an important structural unit
in naturally occurring quinoline alkaloids, therapeutics,
and synthetic analogues with interesting biological activ-
ities.1 Among them, 1,2-dihydroquinolines have received
substantial attention due to their potential biological activ-
ities arising from their antioxidant properties,2 as well as
being general synthetic building blocks of some other
biologically active compounds.3 However, synthetic
methods of 1,2-dihydroquinolines are limited.4,5 Dihydro-
quinolines can be prepared most often by the addition re-
action of nucleophiles to the quinolinium salts5 and by the
SNAr reaction of the cinnamylamine derivatives, which
are readily obtainable from the Morita–Baylis–Hillman
acetates having an ortho-halogen.6 Recently, an efficient
one-step synthesis of 1-arylsulfonyl-1,2-dihydroquinoline
and 1,2,3,4-tetrahydroquinoline rings using tandem
Michael–aldol cyclization reaction between N-protected
ortho-aminobenzaldehydes and a,b-unsaturated carbonyl
compounds in the presence of a quaternary ammonium
salt was reported.7
The Morita–Baylis–Hillman (MBH) reaction is one of the
most powerful carbon–carbon bond forming reaction.8
Much attention has recently been focused on the intra-9–12
and intermolecular SN2¢ reaction13 of the acetates, imines
or bromo derivatives of the MBH adducts. The intramo-
lecular reaction of the MBH adducts in synthesis of
chromenes,9 benzothiopyrans,10 coumarins11 and
quinolines6,12 have been reported.
Basavaiah and Pandiaraju14 had found that the nucleo-
philic attack of triethyl phosphite (TEP) on the MBH ace-
tates provided allylphosphonates after thermal Michaelis–
Arbuzov (MA) rearrangement.15 In continuation of our in-
terest in the synthesis of heterocyclic compounds using
The reaction mechanism could be proposed as shown in
Scheme 1. Generation of iminophosphorane 5 by the reac-
tion of azide with TEP followed by the SN2¢ displacement
of acetate group affords the dihydroquinoline intermedi-
ate 6. In the next step acetate ion attacks an ethyl group of
the phosphonium salt 6 to result in the formation of the di-
SYNTHESIS 2006, No. 12, pp 1953–1960
x
x.
x
x
.
2
0
0
6
Advanced online publication: 08.05.2006
DOI: 10.1055/s-2006-942383; Art ID: F17605SS
© Georg Thieme Verlag Stuttgart · New York

1954
H.-W. Yi et al.
PAPER
ethyl (1,2-dihydroquinolinyl)phosphonate 7 and ethyl
acetate by the well-known MA rearrangement. The for-
mation of acetoxymethylquinoline derivatives 9 are at-
tributed to the aza-Wittig olefination giving 8 followed by
the aromatization via migration of acetoxy group under
the reaction conditions.18
Table 1 Quinolines 7 and 9 Prepared
Reactant
4a
Time (h)a
Product (yield, %)
10
48
3
7a (79)
7b (59)
7c (91)
–
9a (4)
4b
9b (16)
4c
–
The structures 7 and 9 were established on the basis of
spectroscopic data. Compound 7a, for instance, had the
molecular formula C15H20NO3P, as indicated by HRMS
and EIMS spectra and the base ion peak was observed at
4d
.5b
2b
9d (60)
4e
–
9e (70)
1
m/z = 188 [M+ – PO(OEt)2]. The H NMR spectrum
4f
4b
–
9f (76)
showed a characteristic peak at d = 4.49 as doublet of dou-
blet for the C2-methylene protons, and the C4-methine
proton and methyl protons resonated in d = 7.53 and 3.87
as two singlets. The characteristic signal found in the 31P
NMR spectra appeared at d = 20.86. Compound 9a had
the molecular formula C13H13NO3, as indicated by HRMS
and EIMS spectra and the base ion peak was observed at
m/z = 188 [M+ – COCH3] again. In the 1H NMR spectrum,
the signals from the methylene protons, C4-aromatic pro-
4g
24
48
24
7g (63)
7h (57)
7i (60)
–
–
–
4h
4i
a Reflux temperature.
b Room temperature.
O
OH
OAc
Ac2O, DMAP
r.t., 0.5 h
dioxane
r.t., 1 h to 5 d
(EtO)3P, toluene
0–5 °C, 0.5 h
X
X
Z
X
Z
Z
H
+
34–92%
80–90%
N3
N3
N3
2
3
4
1
OAc
N
reflux
3–48 h
X
Z
X
Z
X
Z
– EtOAc
57–91%
N
N
P
OAc
OEt
OEt
O
P
P(OEt)3
EtO
OEt
OEt
6
7
5
r.t. or reflux
0.5–48 h
OAc
NaOH,THF
reflux, 2 h
X
CH2OAc
R
X
X
CH2OH
91%
4–76%
N
N
R
N
R
10
9
8
1
a
b
c
3, 4, 5, 7
Z
R
X
H
X
9, 10
X
H
H
OMe
OMe
OMe
Me
a
b
c
d
e
f
a
b
c
d
e
f
CO2Me
CO2Me
CO2Me
COMe
COMe
COMe
NO2
OMe
H
NO2
NO2
OMe
H
OMe
NO2
OMe
Me
NO2
OMe
Me
g
h
i
H
CN
CN
NO2
CN
OMe
Scheme 1
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Diethylphosphono-1,2-dihydroquinolines and 3-Acetoxymethylquinolines
1955
were dried over anhyd MgSO4 and the solvent was evaporated in
vacuo. The resulting mixture was chromatographed on silica gel
eluting with hexane–EtOAc (7:1) to afford recovered starting alde-
hyde (4.80 g, 53%) and the desired 1c (1.86 g, 21%) as a pale-yel-
low needle-like solid after crystallization with Et2O–PE; mp 81 °C.
IR (KBr): 2876, 2858, 2134, 2096, 1686, 1610, 1493, 1291 cm–1.
1H NMR (CDCl3): d = 3.84 (s, 3 H, CH3), 7.19–7.21 (m, 2 H, arom),
7.36–7.37 (m, 1 H, arom), 10.32 (s, 1 H, CHO).
ton and two methyl protons appeared as four singlets at
d = 5.24, 7.99, 2.18 and 4.11 ppm. The 13C NMR spectrum
showed carbonyl carbon and C2-carbon signals at d =
1
170.79 and 159.99 ppm, respectively. These H and 13C
NMR values are in good agreement with those reported
for a similar system.18,19 In addition, hydrolysis of 9b with
sodium hydroxide in refluxing aqueous tetrahydrofuran
gave alcohol 10b. On examining the 1H NMR spectrum of
10b we identified O-methyl peak at d = 4.16 ppm, meth-
ylene peak at d = 4.82 ppm, OH peak at d = 2.33 ppm, and
C4-aromatic peak at d = 8.16 ppm as all singlets.
13C NMR (CDCl3): d = 55.68, 110.64, 120.26, 123.39, 127.34,
135.74, 156.74, 188.17.
Anal. Calcd for C8H7N3O2: C, 54.24; H, 3.98; N, 23.72. Found: C,
54.11; H, 3.85; N, 23.60.
(EtCO)2O
DMAP
0–5 °C, 0.5 h
OCOEt
CO2Me
Methyl 3-(2-Azido-5-nitrophenyl)-3-hydroxy-2-methylenepro-
panoate (3b)
O2N
3b
A mixture of 2-azido-5-nitrobenzaldehyde (1b; 1.92 g, 10 mmol),
methyl acrylate (2.70 mL, 30 mmol) and DABCO (1.12 g, 10
mmol) was stirred without solvent for 1 h at r.t. The reaction mix-
ture was diluted with H2O (10 mL) and extracted with CH2Cl2 (3 ×
20 mL). The combined organic layers were dried over anhyd
MgSO4 and the solvent was evaporated in vacuo. The resulting mix-
ture was chromatographed on silica gel eluting with hexane–EtOAc
(3:1) to afford 3b (2.56 g, 92%) as a yellow solid after crystalliza-
tion with Et2O–PE; mp 74–76 °C.
97%
N3
4j
(EtO)3P
toluene
reflux, 48 h
O2N
CH2OCOEt
OMe
7b
+
N
(46%)
IR (KBr): 3517, 2119, 1693, 1586, 1518, 1342, 1285 cm–1.
1H NMR (CDCl3): d = 3.35 (d, J = 5.5 Hz, 1 H, OH), 3.79 (s, 3 H,
OCH3), 5.71 (s, 1 H, CH), 5.82 (d, J = 5.5 Hz, 1 H, CH), 6.39 (s, 1
H, CH), 7.28 (d, J = 8.4 Hz, 1 H, arom), 8.24 (dd, J = 2.6, 8.4 Hz, 1
H, arom), 8.42 (d, J = 2.6 Hz, 1 H, arom).
9j (16%)
Scheme 2
13C NMR (CDCl3): d = 52.21, 67.23, 118.38, 123.85, 124.39,
In conclusion, we have successfully synthesized several
1,2-dihydroquinoline derivatives and 3-acetoxymethyl-
quinoline derivatives from the reaction of the MBH ace-
tates of 2-azidobenzaldehydes derived from methyl
acrylate, MVK and acrylonitrile with TEP, thus demon-
strating the efficacy of the Morita–Baylis–Hillman ad-
ducts in organic synthesis.
127.36, 133.44, 139.88, 143.78, 144.56, 166.49.
Anal. Calcd for C11H10N4O5: C, 47.49; H, 3.62; N, 20.14. Found: C,
47.31; H, 3.50; N, 19.92.
Methyl 3-(2-Azido-5-methoxyphenyl)-3-hydroxy-2-methylene-
propanoate (3c)
A mixture of 2-azido-5-methoxybenzaldehyde (1c; 1.77 g, 10
mmol), methyl acrylate (2.70 mL, 30 mmol), triethanolamine (1.06
mL, 8 mmol) and DABCO (1.12 g, 10 mmol) in THF (10 mL) was
stirred for 4 d at r.t. The reaction mixture was diluted with H2O (10
mL) and extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were dried over anhyd MgSO4 and the solvent was evaporat-
ed in vacuo. The resulting mixture was chromatographed on silica
gel eluting with hexane–EtOAc (4:1) to afford 3c (1.63 g, 62%) as
a brown oil.
Silica gel 60 (70–230 mesh ASTM) used for column chromatogra-
phy was supplied by E. Merck. Analytical TLC was carried out on
Merck silica gel 60 F254 TLC plates. Melting points were taken us-
ing an Electrothermal melting point apparatus and are uncorrected.
Microanalyses were obtained using a Carlo Erba EA 1180 element
analyzer. Electron impact (EI) and high resolution mass spectra
(HRMS) were obtained using a Jeol SX 102 mass spectrometer. IR
spectra were recorded on a Nicolet Magna 550 FTIR spectrometer.
The 1H, 13C and 31P NMR spectra were measured on a Gemini 300
spectrometer using CDCl3 at 300 MHz, 75 MHz and 121 MHz, re-
spectively. All chemical shifts are reported in ppm relative to TMS
or (PhO)3PO. The coupling constants (J) are expressed in Hz.
IR (KBr): 3479, 2122, 1722, 1631, 1607, 1494, 1438, 1287 cm–1.
1H NMR (CDCl3): d = 3.29 (d, J = 5.2 Hz, 1 H, OH), 3.77 (s, 3 H,
OCH3), 3.80 (s, 3 H, OCH3), 5.65 (s, 1 H, CH), 5.78 (d, J = 5.2 Hz,
1 H, CH), 6.32 (s, 1 H, CH), 6.88 (dd, J = 2.7, 8.9 Hz, 1 H, arom),
7.03 (d, J = 2.7 Hz, 1 H, arom), 7.08 (d, J = 8.9 Hz, 1 H, arom).
Methyl acrylate, MVK, acrylonitrile, DABCO, DMAP and TEP
were obtained from Aldrich and were used without further purifica-
tion. The known MBH adducts 3a, 3d and 3g, MBH acetates 4a, 4d,
4g,16b 2-azido-5-nitrobenzaldehyde20 and 5-methoxy-2-nitro-
benzaldehyde21 were prepared according to the literature proce-
dures. Petroleum ether (PE) used refers to the fraction boiling in the
range 30–60 °C.
13C NMR (CDCl3): d = 52.09, 55.56, 67.90, 113.24, 114.70, 119.12,
126.64, 129.53, 133.03, 140.77, 156.97, 166.93.
Anal. Calcd for C12H13N3O4: C, 54.75; H, 4.98; N, 15.96. Found: C,
54.61; H, 4.73; N, 15.82.
3-[1-(2-Azido-5-nitrophenyl)-1-hydroxy]methyl-3-buten-2-one
(3e)
A mixture of 2-azido-5-nitrobenzaldehyde (1b; 1.92 g, 10 mmol),
MVK (2.50 mL, 30 mmol) and DABCO (0.22 g, 2 mmol) in diox-
ane (15 mL) was stirred for 1.5 h at 0–5 °C. The reaction mixture
was diluted with H2O (10 mL) and extracted with CH2Cl2 (3 × 30
mL). The combined organic layers were dried over anhyd MgSO4
and the solvent was evaporated in vacuo. The resulting mixture was
2-Azido-5-methoxybenzaldehyde (1c)
A mixture of 5-methoxy-2-nitrobenzaldehyde (9.06 g, 50 mmol)
and NaN3 (6.50 g, 100 mmol) in HMPA (100 mL) was stirred for 70
h at 60 °C. The reaction mixture was diluted with H2O (300 mL) and
extracted with EtOAc (3 × 100 mL). The combined organic layers
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

1956
H.-W. Yi et al.
PAPER
chromatographed on silica gel eluting with hexane–EtOAc (5:1) to
afford 3e (1.31 g, 50%) as a yellow solid after crystallization with
Et2O–PE; mp 98–99 °C.
IR (KBr): 3490, 2131, 1759, 1607, 1587, 1515, 1344, 1283 cm–1.
1H NMR (CDCl3): d = 2.41 (s, 3 H, CH3), 3.47 (d, J = 5.0 Hz, 1 H,
OH), 5.84 (d, J = 5.0 Hz, 1 H, CH), 5.86 (s, 1 H, CH), 6.26 (s, 1 H,
CH), 7.27 (d, J = 8.8 Hz, 1 H, arom), 8.21 (dd, J = 2.4, 8.8 Hz, 1 H,
arom), 8.36 (d, J = 2.4 Hz, 1 H, arom).
ford 3i (0.39 g, 34%) as a yellow solid after crystallization with
Et2O–PE; mp 65–66 °C.
IR (KBr): 3451, 2225, 2135, 1610, 1493, 1470, 1295 cm–1.
1H NMR (CDCl3): d = 2.85 (d, J = 5.2 Hz, 1 H, OH), 3.82 (s, 3 H,
OCH3), 5.52 (d, J = 5.2 Hz, 1 H, CH), 6.05 (s, 1 H, CH), 6.08 (s, 1
H, CH), 6.94 (dd, J = 3.1, 8.8 Hz, 1 H, arom), 7.04 (d, J = 3.1 Hz, 1
H, arom), 7.11 (d, J = 8.8 Hz, 1 H, arom).
13C NMR (CDCl3): d = 55.64, 69.51, 113.02, 115.74, 116.73,
119.44, 124.98, 129.36, 130.66, 130.97, 157.15.
13C NMR (CDCl3): d = 26.56, 66.83, 177.73, 118.97, 123.87,
124.68, 127.82, 133.78, 144.15, 147.86, 200.13.
Anal. Calcd for C11H10N4O2: C, 57.39; H, 4.38; N, 24.34. Found: C,
57.22; H, 4.27; N, 24.15.
Anal. Calcd for C11H10N4O4: C, 50.38; H, 3.84; N, 21.37. Found: C,
50.25; H, 3.67; N, 21.18.
Methyl 3-Acetoxy-3-(2-azido-5-nitrophenyl)-2-methylene-
propanoate (4b)
3-[1-(2-Azido-5-methoxyphenyl)-1-hydroxy]methyl-3-buten-2-
one (3f)
To a stirred solution of 3b (1.39 g, 5 mmol) in CH2Cl2 (10 mL) were
added Ac2O (0.71 mL, 7.5 mmol) and DMAP (0.12 g, 1 mmol) at
r.t. After stirring at r.t. for 30 min the reaction mixture was diluted
with 10% aq NaHCO3 solution and extracted with CH2Cl2 (3 × 20
mL). The combined organic layers were dried over anhyd MgSO4
and the solvent was evaporated in vacuo. The resulting mixture was
chromatographed on silica gel eluting with hexane–EtOAc (3:1) to
afford 4b (1.44 g, 90%) as a yellow solid after crystallization with
Et2O; mp 79–80 °C.
A mixture of 2-azido-5-methoxybenzaldehyde (1c; 0.89 g, 5 mmol),
MVK (1.25 mL, 15 mmol) and DMAP (0.12 g, 0.2 mmol) in DMF
(10 mL) was stirred for 36 h at r.t.22 The reaction mixture was dilut-
ed with H2O (10 mL) and extracted with EtOAc (3 × 20 mL). The
combined organic layers were dried over anhyd MgSO4 and the sol-
vent was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane–EtOAc (3:1) to afford 3f
(0.42 g, 34%) as an oil.
IR (KBr): 3421, 2124, 1675, 1607, 1286, 1233 cm–1.
IR (KBr): 2129, 1752, 1711, 1635, 1587, 1355, 1297 cm–1.
1H NMR (CDCl3): d = 2.38 (s, 3 H, CH3), 3.59 (br s, 1 H, OH), 3.79
(s, 3 H, OCH3), 5.78 (d, J = 4.9 Hz, 1 H, CH), 5.79 (s, 1 H, CH),
6.18 (s, 1 H, CH), 6.87 (dd, J = 3.0, 8.9 Hz, 1 H, arom), 7.02 (d, J =
3.0 Hz, 1 H, arom), 7.06 (d, J = 8.9 Hz, 1 H, arom).
1H NMR (CDCl3): d = 2.15 (s, 3 H, CH3), 3.76 (s, 3 H, OCH3), 5.79
(s, 1 H, CH), 6.51 (s, 1 H, CH), 6.89 (s, 1 H, CH), 7.30 (d, J = 8.4
Hz, 1 H, arom), 8.21 (d, J = 2.6 Hz, 1 H, arom), 8.25 (dd, J = 2.6,
8.4 Hz, 1 H, arom).
13C NMR (CDCl3): d = 26.32, 55.49, 67.33, 113.17, 114.43, 119.00,
127.24, 129.27, 133.32, 148.69, 156.91, 200.45.
13C NMR (CDCl3): d = 20.84, 52.22, 67.48, 118.74, 124.15, 124.98,
128.18, 130.32, 137.40, 144.42, 144.69, 164.91, 169.11.
Anal. Calcd for C12H13N3O3: C, 58.29; H, 5.30; N, 16.99. Found: C,
58.05; H, 5.21; N, 16.76.
Anal. Calcd for C13H12N4O6: C, 48.75; H, 3.78; N, 17.49. Found: C,
48.63; H, 3.67; N, 17.30.
3-(2-Azido-5-nitrophenyl)-3-hydroxy-2-methylenepropane-
nitrile (3h)
Methyl 3-Acetoxy-3-(2-azido-5-methoxyphenyl)-2-methylene-
propanoate (4c)
The procedure was the same as described above using 3c (1.32 g, 5
mmol) to afford 4c (1.22 g, 80%) as a white solid after crystalliza-
tion with PE; mp 79 °C.
A mixture of 2-azido-5-nitrobenzaldehyde (1b; 1.92 g, 10 mmol),
acrylonitrile (2.35 mL, 30 mmol) and DABCO (1.12 g, 10 mmol) in
dioxane (15 mL) was stirred for 5 d at r.t. The reaction mixture was
diluted with H2O (10 mL) and extracted with CH2Cl2 (3 × 30 mL).
The combined organic layers were dried over anhyd MgSO4 and the
solvent was evaporated in vacuo. The resulting mixture was chro-
matographed on silica gel eluting with hexane–EtOAc (5:1) to af-
ford 3h (1.62 g, 66%) as a yellow solid after crystallization with
Et2O–PE; mp 82–83 °C.
IR (KBr): 2118, 1751, 1709, 1635, 1605, 1493, 1299 cm–1.
1H NMR (CDCl3): d = 2.12 (s, 3 H, CH3), 3.75 (s, 3 H, OCH3), 3.79
(s, 3 H, OCH3), 5.64 (s, 1 H, CH), 6.43 (s, 1 H, CH), 6.85 (d, J = 2.7
Hz, 1 H, arom), 6.86 (s, 1 H, CH), 6.90 (dd, J = 2.7, 8.5 Hz, 1 H,
arom) 7.10 (d, J = 8.5 Hz, 1 H, arom).
13C NMR (CDCl3): d = 20.90, 52.12, 55.54, 68.38, 113.94, 114.44,
119.41, 127.66, 129.90, 130.39, 138.36, 156.70, 165.35, 169.25.
IR (KBr): 3521, 2223, 2131, 1610, 1590, 1522, 1486, 1340 cm–1.
1H NMR (CDCl3): d = 2.65 (d, J = 4.9 Hz, 1 H, OH), 5.64 (d, J =
4.9 Hz, 1 H, CH), 6.14 (s, 1 H, CH), 6.20 (s, 1 H, CH), 7.32 (d, J =
8.5 Hz, 1 H, arom), 8.29 (dd, J = 2.4, 8.5 Hz, 1 H, arom), 8.45 (d,
J = 2.4 Hz, 1 H, arom).
13C NMR (CDCl3): d = 68.51, 116.21, 118.71, 123.72, 124.19,
125.37, 131.34, 131.72, 143.74, 144.84.
Anal. Calcd for C14H15N3O5: C, 55.08; H, 4.95; N, 13.76. Found: C,
54.89; H, 4.90; N, 13.62.
3-[1-Acetoxy-1-(2-azido-5-nitrophenyl)]methyl-3-buten-2-one
(4e)
The procedure was the same as described above using 3e (1.31 g, 5
mmol) to afford 4e (1.37 g, 90%) as an orange solid after crystalli-
zation with PE; mp 112–113 °C.
Anal. Calcd for C10H7N5O3: C, 48.98; H, 2.88; N, 28.56. Found: C,
48.73; H, 2.75; N, 28.39.
IR (KBr): 2124, 1738, 1673, 1585, 1515, 1483, 1373 cm–1.
3-(2-Azido-5-methoxyphenyl)-3-hydroxy-2-methylene-
propanenitrile (3i)
1H NMR (CDCl3): d = 2.13 (s, 3 H, CH3), 2.38 (s, 3 H, CH3), 6.00
(s, 1 H, CH), 6.36 (s, 1 H, CH), 6.92 (s, 1 H, CH), 7.28 (d, J = 8.8
Hz, 1 H, arom), 8.13 (d, J = 2.7 Hz, 1 H, arom), 8.23 (dd, J = 2.4,
8.8 Hz, 1 H, arom).
13C NMR (CDCl3): d = 20.35, 26.10, 66.97, 118.18, 119.47, 123.59,
124.58, 125.28, 130.68, 144.55, 145.52, 169.11, 197.05.
A mixture of 2-azido-5-methoxybenzaldehyde (1c; 0.89 g, 5 mmol),
acrylonitrile (0.99 mL, 15 mmol) and DABCO (0.12 g, 1 mmol) in
dioxane (10 mL) was stirred for 5 d at r.t. The reaction mixture was
diluted with H2O (10 mL) and extracted with CH2Cl2 (3 × 20 mL).
The combined organic layers were dried over anhyd MgSO4 and the
solvent was evaporated in vacuo. The resulting mixture was chro-
matographed on silica gel eluting with hexane–EtOAc (3:1) to af-
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Diethylphosphono-1,2-dihydroquinolines and 3-Acetoxymethylquinolines
1957
Anal. Calcd for C13H12N4O5: C, 51.32; H, 3.98; N, 18.41. Found: C,
51.19; H, 3.76; N, 18.27.
H, NCH2), 7.08 (dd, J = 7.3, 7.6 Hz, 1 H, arom), 7.25 (d, J = 7.6 Hz,
1 H, arom), 7.31 (dd, J = 7.6, 8.2 Hz, 1 H, arom), 7.49 (d, J = 8.2
Hz, 1 H, arom), 7.53 (s, 1 H, C4-H).
3-[1-Acetoxy-1-(2-azido-5-methoxyphenyl)]methyl-3-buten-2-
one (4f)
The procedure was the same as described above using 3f (0.49 g, 2
mmol) to afford 4f (0.48 g, 83%) as an oil.
IR (KBr): 2122, 1746, 1681, 1609, 1495, 1369, 1289, 1230 cm–1.
13C NMR (CDCl3): d = 15.92, 43.20, 51.92, 62.80, 120.63, 123.19,
125.16, 125.58, 129.04, 130.53, 134.91, 139.68, 165.29.
31P NMR [CDCl3/(PhO)3PO]: d = 20.86.
EIMS: m/z (%) = 325 (55) [M+], 310 (24), 268 (40), 188 (100).
1H NMR (CDCl3): d = 2.10 (s, 3 H, CH3), 2.36 (s, 3 H, CH3), 3.78
(s, 3 H, OCH3), 5.84 (s, 1 H, CH), 6.27 (s, 1 H, CH), 6.81 (d, J = 3.1
Hz, 1 H, arom), 6.88 (dd, J = 3.1, 8.5 Hz, 1 H, arom), 6-90 (s, 1 H,
CH), 7.09 (d, J = 8.5 Hz, 1 H, arom).
13C NMR (CDCl3): d = 20.84, 26.14, 55.42, 67.62, 114.05, 114.21,
119.36, 127.04, 130.22, 135.12, 146.26, 156.59, 169.17, 197.02.
HRMS (EI): m/z calcd for C15H20NO5P: 325.1080; found:
325.1085.
3-Acetoxymethyl-2-methoxyquinoline (9a)
White solid; yield: 4%; mp 69–70 °C.
IR (KBr): 1736, 1629, 1575, 1478, 1464, 1251 cm–1.
1H NMR (CDCl3): d = 2.18 (s, 3 H, CH3), 4.11 (s, 3 H, OCH3), 5.24
(s, 2 H, CH2), 7.39 (dd, J = 7.9, 8.2 Hz, 1 H, arom), 7.62 (dd, J =
7.0, 7.9 Hz, 1 H, arom), 7.73 (d, J = 7.0 Hz, 1 H, arom), 7.85 (d,
J = 8.2 Hz, 1 H, arom), 7.99 (s, 1 H, C4-H).
13C NMR (CDCl3): d = 20.99, 53.63, 61.38, 120.33, 124.21, 125.41,
126.96, 127.45, 129.56, 136.93, 146.20, 159.99, 170.79.
Anal. Calcd for C14H15N3O4: C, 58.13; H, 5.23; N, 14.53. Found: C,
57.89; H, 5.07; N, 14.38.
3-Acetoxy-3-(2-azido-5-nitrophenyl)-2-methylenepropane-
nitrile (4h)
The procedure was the same as described above using 3h (1.23 g, 5
mmol) to afford 4h (1.22 g, 85%) as a yellow solid after crystalliza-
tion with EtOAc; mp 94–95 °C.
EIMS: m/z (%) = 231 (51) [M+], 188 (100), 142 (12).
HRMS (EI): m/z calcd for C13H13NO3: 231.0896; found: 231.0892.
IR (KBr): 2234, 2131, 1759, 1607, 1587, 1515, 1485, 1344 cm–1.
1H NMR (CDCl3): d = 2.24 (s, 3 H, CH3), 6.15 (s, 2 H, 2 × CH), 6.59
(s, 1 H, CH), 7.33 (d, J = 8.8 Hz, 1 H, arom), 8.31 (dd, J = 2.4, 8.8
Hz, 1 H, arom), 8.39 (d, J = 2.4 Hz, 1 H, arom).
3-Carbomethoxy-1-diethylphosphono-6-nitro-1,2-dihydro-
quinoline (7b)
Yellow solid; yield: 59%; mp 99–100 °C.
13C NMR (CDCl3): d = 20.77, 68.50, 115.44, 118.86, 120.76,
IR (KBr): 1716, 1656, 1606, 1578, 1513, 1488, 1330, 1281 cm–1.
123.33, 125.60, 128.08, 133.79, 143.96, 144.64, 168.85.
1H NMR (CDCl3): d = 1.32 (td, J = 0.9, 7.0 Hz, 6 H, CH3), 3.86 (s,
3 H, OCH3), 4.03–4.22 (m, 4 H, OCH2), 4.52 (dd, J = 1.2, 6.0 Hz, 2
H, NCH2), 7.49 (s, 1 H, C4-H), 7.61 (d, J = 9.2 Hz, 1 H, arom), 8.10
(d, J = 1.2 Hz, 1 H, arom), 8.11 (dd, J = 2.4, 9.2 Hz, 1 H, arom).
13C NMR (CDCl3): d = 15.96, 43.63, 52.24, 63.66, 120.54, 124.20,
125.25, 125.64, 126.77, 133.03, 142.74, 145.82, 164.51.
31P NMR [CDCl3/(PhO)3PO]: d = 19.45.
EIMS: m/z (%) = 370 (28) [M+], 355 (17), 341 (15), 313 (32), 255
Anal. Calcd for C12H9N5O3: C, 50.18; H, 3.16; N, 24.38. Found: C,
50.03; H, 3.01; N, 24.09.
3-Acetoxy-3-(2-azido-5-methoxyphenyl)-2-methylenepropane-
nitrile (4i)
The procedure was the same as described above using 3i (0.46 g, 2
mmol) to afford 4i (0.44 g, 81%) as a yellow solid after crystalliza-
tion with Et2O–PE; mp 84–85 °C.
IR (KBr): 2229, 2134, 2103, 1740, 1609, 1497, 1294 cm–1.
(13), 233 (100).
1H NMR (CDCl3): d = 2.19 (s, 3 H, CH3), 3.82 (s, 3 H, OCH3), 6.07
(s, 2 H, 2 × CH), 6.55 (s, 1 H, CH), 6.95 (dd, J = 2.7, 8.8 Hz, 1 H,
arom), 7.05 (d, J = 2.7 Hz, 1 H, arom), 7.11 (d, J = 8.8 Hz, 1 H,
arom).
HRMS (EI): m/z calcd for C15H19N2O7P: 370.0931; found:
370.0919.
3-Acetoxymethyl-2-methoxy-6-nitroquinoline (9b)
White solid; yield: 16%; mp 144–145 °C.
13C NMR (CDCl3): d = 20.88, 55.63, 69.30, 112.99, 115.57, 115.98,
IR (KBr): 1744, 1632, 1580, 1528, 1496, 1474, 1406, 1339, 1240
cm–1.
1H NMR (CDCl3): d = 2.22 (s, 3 H, CH3), 4.15 (s, 3 H, OCH3), 5.25
(s, 2 H, CH2), 7.91 (d, J = 9.2 Hz, 1 H, arom), 8.11 (s, 1 H, C4-H),
8.38 (dd, J = 2.4, 9.2 Hz, 1 H, arom), 8.67 (d, J = 2.4 Hz, 1 H, arom).
13C NMR (CDCl3): d = 20.83, 54.24, 60.62, 123.14, 123.28, 123.69,
123.99, 128.23, 136.98, 143.90, 149.19, 162.08, 170.45.
119.37, 121.71, 127.86, 129.59, 132.99, 157.05, 169.02.
Anal. Calcd for C13H12N4O3: C, 57.35; H, 4.44; N, 20.58. Found: C,
57.20; H, 4.29; N, 20.47.
1-Diethylphosphono-1,2-dihydroquinolines 7 and 3-Acetoxy-
methylquinolines 9; General Procedure
To a stirred solution of 4 (4 mmol) in toluene (5 mL) was slowly
added (EtO)3P (0.82 mL, 4.8 mmol) in toluene (5 mL) at 0–5 °C.
The reaction mixture was stirred at r.t. for 30 min, and then at reflux
temperature for the time indicated in Table 1. The reaction mixture
was concentrated under reduced pressure and the residue was chro-
matographed on silica gel eluting with hexane–EtOAc (6:1 → 3:1)
to afford 7 and/or 9 as a solid after crystallization with Et2O or PE.
EIMS: m/z (%) = 276 (17) [M+], 233 (100), 217 (12), 187 (19).
HRMS (EI): m/z calcd for C13H12N2O5: 276.0747; found: 276.0743.
3-Carbomethoxy-1-diethylphosphono-6-methoxy-1,2-dihydro-
quinoline (7c)
White solid; yield: 91%; mp 124–126 °C.
IR (KBr): 1709, 1638, 1609, 1572, 1495, 1436 cm–1.
1H NMR (CDCl3): d = 1.26 (t, J = 7.0 Hz, 6 H, CH3), 3.80 (s, 3 H,
OCH3), 3.82 (s, 3 H, OCH3), 3.93–4.14 (m, 4 H, OCH2), 4.41 (d,
J = 8.5 Hz, 2 H, NCH2), 6.75 (d, J = 2.7 Hz, 1 H, arom), 6.84 (dd,
J = 2.7, 8.9 Hz, 1 H, arom), 7.36 (d, J = 8.9 Hz, 1 H, arom), 7.46 (s,
1 H, C4-H).
3-Carbomethoxy-1-diethylphosphono-1,2-dihydroquinoline
(7a)
White solid; yield: 79%; mp 31–32 °C.
IR (KBr): 1721, 1640, 1600, 1567, 1487, 1435 cm–1.
1H NMR (CDCl3): d = 1.31 (td, J = 0.9, 7.3 Hz, 6 H, CH3), 3.87 (s,
3 H, OCH3), 3.98–4.20 (m, 4 H, OCH2), 4.49 (dd, J = 1.2, 7.6 Hz, 2
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

1958
H.-W. Yi et al.
PAPER
3-Cyano-1-diethylphosphono-6-nitro-1,2-dihydroquinoline
13C NMR (CDCl3): d = 15.99, 43.33, 52.02, 55.52, 62.73, 113.43,
116.12, 121.94, 126.18, 126.72, 132.76, 134.86, 155.45, 165.34.
(7h)
Yellow solid; yield: 57%; mp 65–67 °C.
31P NMR [CDCl3/(PhO)3PO]: d = 21.30.
IR (KBr): 2221, 1632, 1607, 1573, 1512, 1483, 1392, 1347, 1280
cm–1.
1H NMR (CDCl3): d = 1.34 (t, J = 7.0 Hz, 6 H, CH3), 4.05–4.24 (m,
4 H, OCH2), 4.42 (d, J = 6.4 Hz, 2 H, NCH2), 7.23 (s, 1 H, C4-H),
7.60 (d, J = 9.4 Hz, 1 H, arom), 8.05 (s, 1 H, arom), 8.16 (dd, J =
2.7, 9.2 Hz, 1 H, arom).
13C NMR (CDCl3): d = 15.92, 44.34, 63.91, 107.31, 115.96, 120.89,
123.82, 123.95, 126.04, 138.22, 142.82, 144.89.
31P NMR [CDCl3/(PhO)3PO]: d = 18.77.
EIMS: m/z (%) = 337 (36) [M+], 308 (14), 280 (54), 200 (100), 138
EIMS: m/z (%) = 355 (21) [M+], 298 (8), 218 (100).
HRMS (EI): m/z calcd for C16H22NO6P: 355.1186; found:
355.1183.
3-Acetoxymethyl-2-methylquinoline (9d)
Pink solid; yield: 60%; mp 94–95 °C (Lit.18 94–95 °C).
IR (KBr): 1736, 1620, 1607, 1564, 1490, 1425, 1366, 1241 cm–1.
1H NMR (CDCl3): d = 2.16 (s, 3 H, CH3), 2.76 (s, 3 H, CH3), 5.29
(s, 2 H, CH2), 7.51 (dd, J = 8.1, 8.1 Hz, 1 H, arom), 7.70 (dd, J =
8.4, 8.4 Hz, 1 H, arom), 7.80 (d, J = 8.1 Hz, 1 H, arom), 8.03 (d,
J = 8.4 Hz, 1 H, arom), 8.09 (s, 1 H, C4-H).
(55), 111 (31).
13C NMR (CDCl3): d = 20.85, 22.84, 63.86, 126.05, 126.61, 127.45,
127.64, 128.37, 129.67, 136.05, 147.41, 157.73, 170.61.
HRMS (EI): m/z calcd for C14H16N3O5P: 337.0829; found:
337.0822.
EIMS: m/z (%) = 215 (18) [M+], 155 (100).
3-Cyano-1-diethylphosphono-6-methoxy-1,2-dihydroquinoline
(7i)
HRMS (EI): m/z calcd for C13H13NO2: 215.0947; found: 215.0948.
Yellow oil; yield: 60%.
IR (KBr): 2210, 1625, 1606, 1569, 1493, 1465, 1392, 1258 cm–1.
1H NMR (CDCl3): d = 1.29 (t, J = 7.0 Hz, 6 H, CH3), 3.80 (s, 3 H,
OCH3), 3.97–4.16 (m, 4 H, OCH2), 4.28 (d, J = 9.5 Hz, 2 H, NCH2),
6.70 (d, J = 2.7 Hz, 1 H, arom), 6.88 (dd, J = 2.7, 8.9 Hz, 1 H, arom),
7.18 (s, 1 H, C4-H), 7.35 (d, J = 8.9 Hz, 1 H, arom).
13C NMR (CDCl3): d = 15.96, 44.28, 55.54, 63.06, 106.37, 112.80,
117.03, 122.55, 125.48, 125.56, 132.08, 139.94, 155.76.
31P NMR [CDCl3/(PhO)3PO]: d = 20.60.
EIMS: m/z (%) = 322 (33) [M+], 265 (12), 185 (100).
3-Acetoxymethyl-2-methyl-6-nitroquinoline (9e)
White solid; yield: 70%; mp 158–159 °C.
IR (KBr): 1752, 1620, 1571, 1509, 1480, 1448, 1345, 1238 cm–1.
1H NMR (CDCl3): d = 2.20 (s, 3 H, CH3), 2.81 (s, 3 H, CH3), 5.32
(s, 2 H, CH2), 8.15 (d, J = 9.5 Hz, 1 H, arom), 8.28 (s, 1 H, C4-H),
8.47 (dd, J = 2.4, 9.2 Hz, 1 H, arom), 8.78 (d, J = 2.7 Hz, 1 H, arom).
13C NMR (CDCl3): d = 20.75, 23.17, 63.02, 122.94, 124.15, 125.37,
130.11, 136.56, 145.06, 149.22, 162.72, 170.40.
EIMS: m/z (%) = 260 (12) [M+], 200 (100), 192 (10), 154 (11).
HRMS (EI): m/z calcd for C13H12N2O4: 260.0798; found: 260.0790.
HRMS (EI): m/z calcd for C15H19N2O4P: 322.1084; found:
322.1081.
3-Acetoxymethyl-6-methoxy-2-methylquinoline (9f)
White solid; yield: 76%; mp 105–106 °C.
IR (KBr): 1738, 1610, 1497, 1458, 1376, 1252 cm–1.
Methyl 3-Acetoxy-3-(5-nitro-2-triethoxyiminophosphoranyl-
idene)phenyl-2-methylenepropanoate (5b)
1H NMR (CDCl3): d = 2.16 (s, 3 H, CH3), 2.71 (s, 3 H, CH3), 3.92
(s, 3 H, OCH3), 5.26 (s, 2 H, CH2), 7.06 (d, J = 2.7 Hz, 1 H, arom),
7.34 (dd, J = 2.7, 9.2 Hz, 1 H, arom), 7.92 (d, J = 9.2 Hz, 1 H, arom),
7.99 (s, 1 H, C4-H).
13C NMR (CDCl3): d = 16.06, 22.51, 55.43, 63.76, 104.98, 121.97,
122.50, 127.65, 129.68, 134.99, 143.37, 154.98, 157.34, 170.71.
To a stirred solution of 4b (1.28 g, 4 mmol) in toluene (5 mL) was
slowly added (EtO)3P (0.82 mL, 4.8 mmol) in toluene (5 mL) at 0–
5 °C. The reaction mixture was stirred at r.t. for 30 min and concen-
trated under reduced pressure. The residue was chromatographed on
silica gel eluting with hexane–EtOAc (1:1) to afford 5b (1.47 g,
80%) as an oil.
IR (KBr): 1742, 1727, 1633, 1596, 1580, 1495, 1384, 1318, 1023
cm–1.
EIMS: m/z (%) = 245 (48) [M+], 185 (100), 170 (10).
HRMS (EI): m/z calcd for C14H15NO3: 245.1053; found: 245.1050.
1H NMR (CDCl3): d = 1.34 (td, J = 0.6, 7.0 Hz, 9 H, CH3), 2.12 (s,
3 H, CH3), 3.74 (s, 3 H, OCH3), 4.14 (qd, J = 7.0, 7.3 Hz, 6 H,
OCH2), 5.64 (s, 1 H, CH), 6.41 (s, 1 H, CH), 6.87 (d, J = 8.8 Hz, 1
H, arom), 7.24 (s, 1 H, CH), 8.00 (dd, J = 2.7, 8.8 Hz, 1 H, arom),
8.09 (dd, J = 2.7, 3.1 Hz, 1 H, arom).
3-Cyano-1-diethylphosphono-1,2-dihydroquinoline (7g)
Yellow oil; yield: 63%.
IR (KBr): 2209, 1622, 1600, 1565, 1487, 1453, 1392, 1259 cm–1.
1H NMR (CDCl3): d = 1.29 (td, J = 0.9, 7.2 Hz, 6 H, CH3), 3.98–
4.18 (m, 4 H, OCH2), 4.29 (dd, J = 1.2, 8.5 Hz, 2 H, NCH2), 7.08
(dd, J = 7.3, 7.6 Hz, 1 H, arom), 7.17 (d, J = 7.6 Hz, 1 H, arom), 7.21
(s, 1 H, C4-H), 7.31 (dd, J = 7.3, 8.2 Hz, 1 H, arom), 7.44 (d, J = 8.2
Hz, 1 H, arom).
13C NMR (CDCl3): d = 15.97, 44.17, 63.19, 105.38, 117.05, 121.08,
123.71, 124.47, 128.63, 131.33, 139.04, 140.09.
13C NMR (CDCl3): d = 15.98, 21.03, 52.14, 64.61, 68.96, 121.05,
123.25, 123.69, 124.96, 130.47, 138.77, 138.98, 154.38, 165.82,
169.57.
31P NMR [CDCl3/(PhO)3PO]: d = 16.77.
Anal. Calcd for C19H27N2O9P: C, 49.78; H, 5.94; N, 6.11. Found: C,
49.60; H, 5.85; N, 5.90.
31P NMR [CDCl3/(PhO)3PO]: d = 20.13.
EIMS: m/z (%) = 292 (39) [M+], 263 (13), 235 (34), 155 (100).
3-Carbomethoxy-1-diethylphosphono-6-nitro-1,2-dihydro-
quinoline (7b) and 3-Acetoxymethyl-2-methoxy-6-nitroquino-
line (9b)
A stirred solution of iminophosphorane 5b (1.37 g, 3 mmol) in tol-
uene (10 mL) was heated at reflux temperature for 19 h and the sol-
vent was evaporated in vacuo. The residue was chromatographed on
HRMS (EI): m/z calcd for C14H17N2O3P: 292.0978; found:
292.0980.
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

PAPER
Synthesis of 1-Diethylphosphono-1,2-dihydroquinolines and 3-Acetoxymethylquinolines
1959
silica gel eluting with hexane–EtOAc (3:1) to afford 7b (0.72 g,
65%) and 9b (0.18 g, 22%) as solids.
127.50, 128.18, 136.01, 143.86, 148.99, 162.35.
Anal. Calcd for C11H10N2O4: C, 56.41; H, 4.30; N, 11.96. Found: C,
56.32; H, 4.21; N, 11.79.
Methyl 3-(2-Azido-5-nitrophenyl)-2-methylene-3-propanoyl-
oxypropanoate (4j)
To a stirred solution of 3b (1.39 g, 5 mmol) in CH2Cl2 (10 mL) was
added propionic anhydride (0.96 mL, 7.5 mmol) and DMAP (0.12
g, 1 mmol) at r.t. After stirring at r.t. for 30 min the reaction mixture
was diluted with 10% aq NaHCO3 solution and extracted with
CH2Cl2 (3 × 20 mL). The combined organic layers were dried over
anhyd MgSO4 and the solvent was evaporated in vacuo. The result-
ing mixture was chromatographed on silica gel eluting with hex-
ane–EtOAc (3:1) to afford 4j (1.62 g, 97%) as a yellow oil.
Acknowledgment
This study was supported by a grant of University IT Research Cen-
ter Project, Republic of Korea.
References
(1) (a) Michael, J. P. Nat. Prod. Rep. 1997, 14, 605.
(b) Balasubramanian, M.; Keay, J. G. In Comprehensive
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300. (c) Jones, G. In Comprehensive Heterocyclic Chemistry
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IR (KBr): 2130, 1746, 1723, 1634, 1611, 1588, 1528, 1346, 1297
cm–1.
1H NMR (CDCl3): d = 1.17 (t, J = 7.6 Hz, 3 H, CH3), 2.43 (q, J =
7.6 Hz, 2 H, CH2), 3.76 (s, 3 H, OCH3), 5.78 (d, J = 1.2 Hz, 1 H,
CH), 6.50 (s, 1 H, CH), 6.89 (s, 1 H, CH), 7.31 (d, J = 8.9 Hz, 1 H,
arom), 8.21 (d, J = 2.4 Hz, 1 H, arom), 8.25 (dd, J = 2.4, 8.9 Hz, 1
H, arom).
13C NMR (CDCl3): d = 8.85, 27.31, 52.17, 67.32, 118.76, 124.06,
124.94, 128.19, 130.43, 137.50, 144.41, 144.68, 164.94, 172.60.
Anal. Calcd for C14H14N4O6: C, 50.30; H, 4.22; N, 16.76. Found: C,
50.07; H, 4.09; N, 16.53.
(3) (a) Engler, T. A.; Lynch, K. O. Jr.; Chai, W.; Meduna, S. P.
Tetrahedron Lett. 1995, 36, 2713. (b) Engler, T. A.; La
Tessa, K. O.; Iyenger, R.; Chai, W.; Agrios, K. Bioorg. Med.
Chem. 1996, 4, 1755.
(4) (a) Yavari, I.; Ramazani, A.; Esmaili, A. A. J. Chem. Res.,
Synop. 1997, 208. (b) Williamson, N. M.; March, D. R.;
Ward, A. D. Tetrahedron Lett. 1995, 36, 7721.
3-Carbomethoxy-1-diethylphosphono-6-nitro-1,2-dihydro-
quinoline (7b) and 2-Methoxy-6-nitro-3-propanoyloxymethyl-
quinoline (9j)
To a stirred solution of 4g (1.34 g, 4 mmol) in toluene (5 mL) was
slowly added (EtO)3P (0.82 mL, 4.8 mmol) in toluene (5 mL) at 0–
5 °C. The reaction mixture was stirred at r.t. for 30 min, and then at
reflux temperature for 48 h. The reaction mixture was concentrated
under reduced pressure and the residue was chromatographed on
silica gel eluting with hexane–EtOAc (5:1) to afford 7b (0.68 g,
46%) and 9j (0.19 g, 16%) as solids.
(c) Kobayashi, K.; Nakahashi, R.; Shimizu, A.; Kitamura,
T.; Morikawa, O.; Konishi, H. J. Chem. Soc., Perkin Trans.
1 1999, 1547. (d) Yavari, I.; Esmaili, A. A.; Ramazani, A.;
Bolbol–Amiri, A. R. Monatsh. Chem. 1997, 128, 927.
(e) Kikugawa, Y.; Kuramoto, M.; Saito, I.; Yamada, S.-I.
Chem. Pharm. Bull. 1972, 21, 1914. (f) Johnson, W. S.;
Buell, B. G. J. Am. Chem. Soc. 1952, 74, 4517.
(g) Kobayashi, K.; Nagato, S.; Kawakita, M.; Morikawa, O.;
Konishi, H. Chem. Lett. 1995, 575. (h) Kouznetsov, V.;
Palma, A.; Ewert, C.; Varlamov, A. J. Heterocycl. Chem.
1998, 35, 761. (i) Schweizer, E. E.; Smucker, L. D. J. Org.
Chem. 1966, 31, 3146. (j) Arisawa, M.; Theeraladanon, C.;
Nishida, A.; Nakagawa, M. Tetrahedron Lett. 2001, 42,
8029.
9j
White solid; mp 127–128 °C.
IR (KBr): 1742, 1631, 1618, 1583, 1530, 1496, 1404, 1343, 1187
cm–1.
1H NMR (CDCl3): d = 1.24 (t, J = 7.6 Hz, 3 H, CH3), 2.51 (q, J =
7.6 Hz, 2 H, CH2), 4.15 (s, 3 H, OCH3), 5.26 (s, 2 H, CH2), 7.89 (d,
J = 9.2 Hz, 1 H, arom), 8.09 (s, 1 H, C4-H), 8.37 (dd, J = 2.4, 9.2
Hz, 1 H, arom), 8.66 (d, J = 2.4 Hz, 1 H, arom).
13C NMR (CDCl3): d = 9.07, 27.47, 54.21, 60.53, 123.12, 123.25,
123.63, 123.97, 128.16, 136.81, 143.77, 149.10, 162.03, 173.91.
(5) (a) Grignon-Dubois, M.; Diaba, F.; Grellier–Marly, M.-C.
Synthesis 1994, 800. (b) Diaba, F.; Houerou, C. L.; Grignon-
Dubois, M.; Gerval, P. J. Org. Chem. 2000, 65, 907.
(c) Diaba, F.; Lewis, I.; Grignon-Dubois, M.; Navarre, S. J.
Org. Chem. 1996, 61, 4830. (d) Grignon-Dubois, M.;
Diaba, F. J. Chem. Res., Synop. 1998, 660. (e) Maeda, M.
Chem. Pharm. Bull. 1990, 38, 2577. (f) Mani, N. S.; Chen,
P.; Jones, T. K. J. Org. Chem. 1999, 64, 6911. (g)Muren, J.
F.; Weissman, A. J. Med. Chem. 1971, 14, 49.
(6) (a) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Kim, H. S. Tetrahedron
Lett. 2001, 42, 3737. (b) Kim, J. N.; Kim, H. S.; Gong, J. H.;
Chung, Y. M. Tetrahedron Lett. 2001, 42, 8341.
(7) Makino, K.; Hara, O.; Takiguchi, Y.; Katano, T.; Asakawa,
Y.; Hatano, K.; Hamada, Y. Tetrahedron Lett. 2003, 44,
8925.
Anal. Calcd for C14H14N2O5: C, 57.93; H, 4.86; N, 9.65. Found: C,
57.81; H, 4.77; N, 9.46.
3-Hydroxymethyl-2-methoxy-6-nitroquinoline (10b)
A mixture of 9b (0.14 g, 0.5 mmol) and NaOH (0.02 g, 0.5 mmol)
in THF (3 mL) and H2O (1 mL) was stirred at reflux temperature for
2 h. The reaction mixture was concentrated under reduced pressure
and the residue was partitioned between H2O (3 mL) and CH2Cl2
(20 mL). The solvent was removed after drying over anhyd MgSO4
and the residue was crystallized with PE to afford 10b (0.11 g, 91%)
as a yellow solid; mp 160–161 °C.
IR (KBr): 3266, 1629, 1580, 1527, 1476, 1402 cm–1.
1H NMR (CDCl3): d = 2.33 (br s, 1 H, OH), 4.16 (s, 3 H, OCH3),
4.82 (s, 2 H, CH2), 7.91 (d, J = 9.2 Hz, 1 H, arom), 8.16 (s, 1 H, C4-
H), 8.38 (dd, J = 2.4, 9.2 Hz, 1 H, arom), 8.67 (d, J = 2.4 Hz, 1 H,
arom).
(8) For reviews of the Morita–Baylis–Hillman reaction, see:
(a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
4653. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001. (c) Ciganek, E. In Organic
Reactions, Vol. 51; Paquette, L. A., Ed.; Wiley: New York,
13C NMR (CDCl3): d = 54.18, 60.45, 122.95, 123.97, 124.06,
Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York

1960
H.-W. Yi et al.
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(10) Kaye, P. T.; Nocanda, X. W. Synthesis 2001, 2389.
(11) Kaye, P. T.; Musa, M. A.; Nocanda, X. W. Synthesis 2003,
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(12) (a) Familoni, O. B.; Kaye, P. T.; Klass, P. J. Chem. Commun.
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Synthesis 2006, No. 12, 1953–1960 © Thieme Stuttgart · New York