Abstract
An efficient and rapid parallel liquid-phase synthesis of pyrazolines
has been developed. The one-pot three-components reaction of polyethylene
glycol (PEG)-supported acrylate 1 , aldehyde 2 and aryl hydrazine 3 in
the presence of chloramine-T in methanol gave the corresponding
PEG-supported pyrazolines 5 . Cleavage from
the support under mild conditions afforded pyrazolines 6 in good yields (69-91%)
and high purities (91-100%).
Key words
pyrazolines - 1,3-dipolar cycloaddition - soluble
polymer - liquid-phase synthesis - polyethylene
glycol (PEG)
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8
Typical Procedure
for Pyrazoline Synthesis: After combining aldehyde (1.0 mmol),
hydrazine hydrochloride (1.0 mmol) and trioctylamine (TOA, 1.0 mmol)
in MeOH (8 mL) at r.t. for 10 min, PEG-supported acryloyl ester
(0.25 mmol) and chloramine-T (1.0 mmol) were added and the mixture
was stirred for 24 h under N2 . Upon completion of the
reaction, cold Et2 O (30 mL) was added to the reaction mixture
to precipitate the PEG-bound pyrazoline. The precipitate was then
collected on a sintered glass funnel and thoroughly washed with
Et2 O (10 mL × 3). PEG-bound pyrazoline was then
dried under vacuum. Finally, the resulting PEG-bound pyrazoline
was cleaved by 0.1 N MeONa in MeOH (5 mL) at r.t. for 6 h. Cold
Et2 O (30 mL) was added to precipitate the detached PEG-OH.
The polymer was filtered and the combined filtrate was flash passed
through a short column to remove trace amount of PEG and MeONa.
The solvent was removed to give the corresponding crude product.
All compounds listed in Table
[1 1 H NMR, 13 C
NMR, GC-MS and HRMS data. For compound 6p is
as follows: 1 H NMR (500 MHz, CDCl3 ): δ = 1.64
(s, 3 H), 3.24 (d, J = 16.7
Hz, 1 H), 3.65 (d, J = 16.7
Hz, 1 H), 3.76 (s, 3 H), 6.49 (s, 1 H), 6.60 (d, J = 3.4
Hz, 1 H), 6.90 (t, 1 H), 7.08 (d, J = 8.0
Hz, 2 H), 7.24 (m, 2 H), 7.5 (s, 1 H). 13 C
NMR (125 MHz, CDCl3 ): δ = 174.3,
148.0, 143.7, 143.3, 137.9, 129.3, 120.6, 115.0, 111.9, 109.6, 68.9,
53.3, 48.1, 21.3. MS (EI): m/z = 284. HRMS
calcd for C16 H16 N2 O3 ([M + H]+ ):
285.1161. Found: 285.1170.
