810 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 810±811$
Intramolecular Nitrile Imide Cycloadditions onto
the Furan Ring: Synthesis of the New 3a,4-Dihydro-
6H-difuro[3,2-c;3,4-d]pyrazole Skeleton$
Gianluigi Broggini, Giorgio Molteni* and Gaetano Zecchi
Dipartimento di Chimica Organica e Industriale dell'Universita and Centro CNR, Via Golgi 19,
20133, Milano, Italy
Intramolecular nitrile imide cycloadditions onto the furan ring have been exploited in the construction of the hitherto
unknown 3a,4-dihydro-6H-difuro[3,2-c;3,4-d]pyrazole skeleton.
The behaviour of the furan ring as dipolarophile in both
inter- and intra-molecular 1,3-dipolar cycloadditions is a
documented matter.1±3 However, few reports are concerned
with cycloadditions between nitrile imides and furan
derivatives.4±6 In pursuing our interest in the synthesis of
new heterocyclic systems, we have undertaken a study on
the intramolecular reactivity of a series of nitrile imides 4
containing the furan moiety as a potential dipolarophile.
The hydrazonoyl chlorides 3, which we devised as suit-
able precursors of the nitrile imide intermediates 4, were
synthesised as depicted in Scheme 1.%
order to prevent acid-catalysed decomposition of the
products. The assigned structures were supported by 1H
NMR and IR spectroscopy as well as FAB±MS spec-
trometry. In conclusion, intramolecular nitrile imide cyclo-
additions to the furan ring were proven to be an eective
route to the new 3a,4-dihydro-6H-difuro[3,2-c;3,4-d]pyrazole
skeleton. The lability of the latter spiro-tricyclic system must
be underlined and can plausibly be ascribed to the strain of
the dihydrofuran ring.
Experimental
The in situ generation of 4 was usually accomplished by
treating 3 under a nitrogen stream with a twofold molar
excess of silver carbonate in dry dioxane at room tem-
perature. In the case of 3c a better result was obtained by
using silver acetate. However, since extensive formation of
dark-coloured decomposition materials was observed, the
reactions were stopped before the conversion of 3 was
complete; so that some amount of the starting hydrazonoyl
chloride was always recovered. The difuropyrazolines 5 were
isolated in an analytically pure state with yields ranging
from 11±37%. Their chromatographic treatment required
eluents added with a small amount of triethylamine in
Analytical and spectroscopic instruments were as described in a
previous paper.7
Preparation of Acetoacetate 1.ÐA solution of 2-hydroxymethyl-
furan (9.9 g, 0.1 mol) in xylene (20 ml) was treated with 2,2,6-
trimethyl-4H-1,3-dioxin-4-one (14.2 g, 0.1 mol). The mixture was
re¯uxed for 1.5 h. Evaporation of the solvent under reduced
pressure gave crude
ꢀ
1
as an `undistillable' oil (17.6 g, 97%);
1
max/cm (neat) 1745, 1720; ꢁH 2.25 (3 H, s), 3.44 (2 H, s), 5.12
(2 H, s), 6.30±6.45 (2 H, m), 7.40±7.50 (1 H, m); m/z 182 (M ).
Preparation of Hydrazonoyl Chlorides 3. General Procedure.ÐA
solution of sulfuryl chloride (3.35 g, 25 mmol) in dry chloroform
(5 ml) was slowly added (2 h) to a mixture of 1 (4.55 g, 25 mmol)
and sodium hydrogencarbonate (2.10 g, 25 mmol) in dry chloroform
(40 ml), keeping the temperature in the range 0±5 8C. After 1.5 h at
room temperature, chloroform (80 ml) was added, and the mixture
was washed with water (25 ml). The organic layer was dried over
sodium sulfate and the solvent was removed under reduced pressure
1
to aord 2 in the crude state (3.51 g, 65%); ꢀmax/cm (neat) 1760,
1730; ꢁH 2.30 (3 H, s), 4.75 (1 H, s), 5.48 (2 H, s), 6.50±6.80 (2 H,
m), 7.40±7.50 (1 H, m). Crude 2 was dissolved in cold methanol
(45 ml), and sodium acetate (2.72 g, 20 mmol) was added. A cold
aqueous solution of the appropriate arenediazonium chloride
(17 mmol) was added dropwise under vigorous stirring and ice-
cooling. The mixture was allowed to stand overnight with stirring at
room temperature. The solvent was partly removed under reduced
pressure and the resulting mixture was extracted with diethyl
ether (150 ml). The organic layer was washed ®rstly with 5%
aqueous sodium hydrogencarbonate (50 ml), then with water
(100 ml), and dried over sodium sulfate. Evaporation of the solvent
and subsequent crystallisation of the residue from diisopropyl ether
gave the hydrazonoyl chlorides 3 in the pure state.
1
3a (3.48 g, 50%) had mp 118 8C; ꢀmax/cm (Nujol) 3270, 1700;
dH (CDCl3) 5.31 (2 H, s), 6.40 (1 H, dd, J 3.3, 1.6), 6.52 (1 H, d,
J 3.3), 7.00±7.40 (5 H, m), 7.46 (1 H, d, J 1.6), 8.35 (1 H, br s)
(J values in Hz throughout); m/z 278 (M ) (Found: C, 56.06;
H, 4.03; Cl, 12.49; N, 10.13. C13H11ClN2O3 requires C, 56.11;
H, 3.99; Cl, 12.58; N, 10.07%).
1
3b (4.68 g, 60%) had mp 111 8C; ꢀmax/cm (Nujol) 3270, 1700;
a, R H; b, R Cl; c, R F; d, R NO2
dH (CDCl3) 5.30 (2 H, s), 6.35 (1 H, dd, J 3.2, 1.8), 6.50 (1 H, d,
J 3.2), 7.00±7.35 (4 H, m), 7.45 (1 H, d, J 1.8), 8.30 (1 H, br s);
m/z 312 (M ) (Found: C, 49.94; H, 3.26; Cl, 22.49; N, 9.06.
Scheme 1 Reagents and conditions: i, xylene, heat; ii, SO2Cl2
0 8C; iii, ArN2 Cl 0 8C iv, Ag2CO3 (entries a, b, d) or AcOAg
(entry c), dioxane, room temp.
C
13H10Cl2N2O3 requires C, 50.00; H, 3.23; Cl, 22.42; N, 8.98%).
1
3c (3.33 g, 45%) had mp 112 8C; ꢀmax/cm (Nujol) 3270, 1715;
dH (CDCl3) 5.29 (2 H, s), 6.37 (1 H, dd, J 3.2, 1.8), 6.50 (1 H, d,
J 3.2), 6.90±7.30 (4 H, m), 7.48 (1 H, d, J 1.8), 8.30 (1 H, br s);
m/z 296 (M ) (Found: C, 52.77; H, 3.34; N, 9.46. C13H10ClFN2O3
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
%Owing to its instability, the a-chloroacetoacetate 2 was used as a
crude material without full characterisation.
requires C, 52.70; H, 3.40; N, 9.46%).
3d (3.63 g, 45%) had mp 152 8C; ꢀmax/cm (Nujol) 3280, 1710;
1
dH (CDCl3) 5.33 (2 H, s), 6.40 (1 H, dd, J 3.3, 1.7), 6.52 (1 H, d,
J 3.3), 7.30±7.40 (2 H, m), 7.47 (1 H, d, J 1.7), 8.20±8.30 (2 H, m),
Broggini, Gianluigi
