P. Besada et al.
shift of C-6 is affected by the magnitude of the alkyl chain at this
position. Thus, the C-6 resonance for the methylene derivatives
was 0.7 0.3 ppm less shielded than for ethylene derivatives but
1.0 0.3 ppm more shielded than for trimethylene derivatives.
Regarding the C-4 and C-5 signals, C-4 is more shielded than C-5
for all compounds studied showing a similar behavior to that
found for H-4 and H-5. In addition, it is noteworthy that the C-5
resonance is the most affected by both N-2 and C-6 substitution.
In particular, the inclusion of a methyl or a benzyl group at N-2
shifts C-5 signals by 1.3 0.3 ppm to lower frequencies, while the
increase in the alkyl chain length at C-6 shifts the same carbon
signal 2.1 0.4 ppm to higher frequencies. Finally, replacement of
tert-butyldiphenylsilyloxy group by a hydroxyl group has no major
effect on C-5, even for the methylene derivatives.
General procedure for the preparation
of 4-hydroxybutenolides 2b and 2c
A solution of 1b–c (1.7-8.3 mmol), N,N-diisopropylethylamine (4.5
equiv.), 4,5,6,7-tetrachloro-2ꢁ,4ꢁ,5ꢁ,7ꢁ-tetraiodofluorescein dis-
odium salt (rose Bengal; 15 mg) in MeOH (15–35 ml), previously
purged with O2, was irradiated with a 200-W lamp for 4 h at
−78 ◦C, stirring under oxygen atmosphere. After the solvent was
evaporated, the residue was dissolved in CH2Cl2 (30 ml), and
0.12 M oxalic acid in H2O (4 equiv.) was added. The mixture was
stirred for 30 min at room temperature (RT) and extracted with
CH2Cl2 (3 × 30 ml). After removal of the solvent, the residue ob-
tained was rapidly passed through a column chromatography
on silica gel (hexane–EtOAc, 2 : 1) to afford the corresponding
4-hydroxybutenolide as a crude oil.
In conclusion, two series of pyridazin-3(2H)-ones, 6-substituted
and 2,6-disubstituted, were synthesized in moderate yield starting
from easily accessible alkyl furans. For all pyridazinone derivatives
described, a complete assignment of all hydrogen and carbon
NMR signals, using 1D and 2D NMR spectroscopic methods, was
accomplished. The1Hand13CNMRanalysisallowedustocorrelate
the chemical shifts of pyridazine ring atoms with substituents at
N-2 and C-6. The obtained results showed that the 5 position is
affected most by structural changes both in N-2 and in C-6.
5-[2-(tert-Butyldiphenylsilyloxy)ethyl]-5-hydroxy-5H-furan-
2-one (2b)
1
In total, 569 mg was obtained from 1b (610 mg, 1.74 mmol). H
NMR (CDCl3, δ): 7.73 (m, 4H, H-Ph), 7.46 (m, 6H, H-Ph), 7.29 (d, 1H,
J = 5.6 Hz, H3), 6.09 (d, 1H, J = 5.6 Hz, H4), 4.31 (m, 1H, 1H2ꢁ), 3.89
(m, 1H, 1H2ꢁ), 2.34 (m, 1H, 1H1ꢁ), 1.90 (m, 1H, 1H1ꢁ), 1.11 (s, 9H, 3 ×
CH3).
5-[3-(tert-Butyldiphenylsilyloxy)propyl]-5-hydroxy-5H-furan-
2-one (2c)
Experimental
In total, 3.80 g was obtained from 1c (3.02 g, 8.28 mmol).
Spectroscopic data for 2c is in accordance with the literature.[15]
Mass spectra were recorded on VG Autoespec M, MICROTOF
FOCUS, and Bruker FTMS APEX XIII spectrometers. NMR spectra
were recorded on a Bruker ARX400 spectrometer (400.13 MHz
for 1H NMR and 100.62 MHz for 13C NMR) from samples as
approximately 50 mM solutions in CDCl3 or CD3OD at 300 K in
5 mm outside diameter tubes. The chemical shifts were internally
referenced to CDCl3 signals (δ = 7.26 ppm for 1H; δ = 77.0 ppm
for 13C) or CD3OD signals (δ = 4.84 ppm for 1H; δ = 49.05 ppm
for 13C). The pulse conditions were as follows: for the 1H NMR
spectrum, 30◦ pulse flip angle, acquisition time (AQ) = 7.18 s,
relaxation delay (RD) = 1.0 s, spectral width (SW) = 4562.04 Hz,
data points (TD) = 65 536; for the 13C NMR spectrum, 30◦ pulse
flip angle, AQ = 1.42 s, RD = 2.0 s, SW = 23 148.15 Hz, TD =
65 536; for the DEPT-135 spectrum, AQ = 1.42 s, RD = 1.0 s, SW =
23 148.15 Hz, TD = 65 536; for the NOE-difference spectrum, AQ
= 3.98 s, RD = 2.0 s, SW = 8223.69 Hz, TD = 65 536; for the COSY
spectrum, AQ = 0.14 s, RD = 1.49 s, SW = 3597.12 Hz, TD = 1024;
for the gHSQC spectrum, AQ = 0.17 s, RD = 1.5 s, SW = 3041.36 Hz,
TD = 1024; for the HMBC spectrum, AQ = 0.17 s, RD = 1.5 s, SW
= 3041.36 Hz, TD = 1024. Data processing was carried out with
Bruker UXNMR programs.
General procedure for the preparation of pyridazinones
3 and 4
To
a
solution of compound 2a–c (0.7–2.2 mmol) in
ethanol (6–10 ml),asolutionofhydrazinemonohydrateormethyl-
hydrazine (2.5 equiv.) in ethanol (1.5 ml) was added. The reaction
mixture was stirred under reflux for 3 h (2a) or at 0 ◦C for 15 min
(2b–c). After removal of the solvent, the residue was purified by
column chromatography on silica gel to afford the corresponding
pyridazinone.
6-(tert-Butyldiphenylsilyloxymethyl)pyridazin-3(2H)-one (3a)
Yield: 14%; High resolution mass spectrometry-electrospray
ionization (HRMS-ESI): m/z calcd. for C21H25N2O2Si, 365.16798
[M + H]; found 365.16704.
6-(tert-Butyldiphenylsilyloxymethyl)-2-methylpyridazin-
3(2H)-one (4a)
The 2-alkylfurans 1a–c were prepared as described else-
where.[14]
Yield: 41%; HRMS-ESI: m/z calcd. for C22H27N2O2Si, 379.18363
[M + H]; found 379.18331.
5-(tert-Butyldiphenylsilyloxymethyl)-5-methoxy-5H-furan-2-
one (2a)
6-[2-(tert-Butyldiphenylsilyloxy)ethyl]pyridazin-3(2H)-one
(3b)
Compound 2a (1.95 g, 56%) was obtained from 1a (3.06 g,
9.10 mmol) following a previously reported procedure.[14a] 1H
NMR (CDCl3, δ): 7.62 (m, 4H, H-Ph), 7.40 (m, 6H, H-Ph), 7.09 (d, 1H,
J = 5.7 Hz, H3), 6.29 (d, 1H, J = 5.7 Hz, H4), 3.88 (s, 2H, CH2), 3.24 (s,
3H, CH3O), 1.01 (s, 9H, 3xCH3). 13C NMR (CDCl3, δ): 169.8 (C2), 152.1
(C4), 135.6 (CH-Ph), 132.4 (C-Ph), 129.9 (CH-Ph), 127.8 (CH-Ph),
126.1 (C3), 110.3 (C5), 65.2 (CH2), 51.4 (CH3O), 26.7 [(CH3)3], 19.2
[C(CH3)3].
Yield: 34% (two steps); HRMS-ESI: m/z calcd. for C22H27N2O2Si,
379.18363 [M + H]; found 379.18344.
6-[2-(tert-Butyldiphenylsilyloxy)ethyl]-2-methylpyridazin-
3(2H)-one (4b)
Yield: 11% (two steps); HRMS-ESI: m/z calcd. for C23H29N2O2Si,
393.19928 [M + H]; found 393.19894.
c
wileyonlinelibrary.com/journal/mrc
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2011, 49, 437–442
Besada, Pedro
