[α-Aracyl-β-(2-Furyl)]-(E)-Vinyl-1,3,4-Oxadiazoles

The 6-aryl-1-(3-chloropropanoyl)-4-[(E)-1-(2-furyl)methylidene)]-1,2,3,4-tetrahydro-3-pyridazinones (6a-d) were synthesized by the reaction of acid chloride 3 with α-aracyl(β-2-furyl)acrylic acid hydrazides (2a-d) in a high yield, one pot reaction. On the other hand, 2-(2-chloroethyl)-5-[α-aracyl-β-(2-furyl)]-(E)-vinyl-1,3,4-oxadiazoles (7a-d) were also prepared by cyclodehydration of N1[α-aracyl-β-(2-furyl)acroyl-N2[3-chloro-propanoyl] hydrazine derivatives (4a-d). The proposed structures of the products were confirmed by elemental analysis, spectral data and chemical evidence.

The 1 H NMR spectra of compounds (2a-d) exhibit singlet signals at 4.41 for (CH 2 COAr), a singlet at δ 6.67 for olefinic protons, triplet signals at δ 7.07 for (-NH-NH 2 ) and two signals dd for (-NH-NH 2 ) due to the strong electrical quadrupole moment effect [19].In compounds (8a-d) the CH 2 adjacent to the furan ring exhibited a singlet at δ 3.92, the olefinic proton of the unsaturated double bond showed a doublet signal at δ 7.56 and the (-NH-) group a singlet at δ13.23 ppm.
The interaction of α-aracyl-β-( 2 In a parallel experiment using benzene solvent in the presence of acid catalyst (1.0 N HCl) at 80 o C the hydrazine compounds (4a-d) cyclised and only formation of products (6a-d) was noted, as evidenced by TLC after 1h.We believe the liberation of HCl aided the ring closure of the hydrazine derivatives compounds (4a-d) under the reaction conditions at 80 o C to provide compounds (6a-d).These compounds were shown by direct comparison (m.p and mixed m.p) and also by TLC to be identical in all aspects with the authentic products obtained by the action of 1.0 N HCl in benzene solvent with N 1 [α-aracyl-β−(2-furyl)acroyl-N 2 [3-chloropropionyl]hydrazine compounds (4a-d).Acid catalysis proved to be essential and reaction was essentially complete after 30-60 min at 80 o C (ca. 92% yield).The 1 H NMR spectra of (4a-d) exhibited singlet signals for the CH 2 protons at δ 4.41 ppm and also show two doublet signals at 9.8 and 10.11 ppm for the hydrazine (-NH-NH-) group.
The alternative mode of ring closure of N 1 [α-aracyl-β−(2-furyl)acroyl-N 2 [3-chloropropionyl]hydrazine compounds (4a-d), that is attack by the N 1 , would lead to the formation of the corresponding N- (3-chloropropionyl)aminopyrrolines (5a-d) as intermediates.But these N-aminopyrrolines (5) are not formed, and the pyridazinones (6a-d) are the only isolable products obtained from this reaction.We believe that the N-aminopyrrolines (5a-d) are unstable under the acid catalyzed reaction conditions and if formed, they might undergo ring expansion [1b] yielding the corresponding 3(2H) pyridazinones (6a-d).This behavior is in accordance with the reported rearrangements of N-aminophthalimides in acid medium to the corresponding phthalaza-1,4-diones [15].The structure of compounds (6a-d) was confirmed by 1 H NMR (300 MHz), microanalysis and infrared spectral data.The IR spectra show an absorption band for the υC=O stretching vibrations of cyclic carboxamides at 1666-1678 cm -1 , characteristic of the 3(2H) pyridazinone ring, and in the 1725-1733 cm -1 region for the C=O of the open alkylcarboximide, as well as a broad band at 3227-3337 cm -1 characteristic of the NH group.The spectra of compounds (6a-d) (cf, Table 1) are similar to those of 1-benzoyl-6-aryl-4-thienylidene-1,6dihydropyridazin-3-(2H)ones [20].The 1 H and 13 C NMR data showed evidence for the formation of a bicyclic structure as shown in Tables 2 and 3.In compounds (6a-d), as expected, the two olefins (=C-H) have different chemical shifts both in the 1 H and 13 C NMR spectra.These highly conjugated structures show a typical two singlet signal for the C-H in the 1 H NMR spectrum at δ 6.6-6.7 and 7.08-7.13for CH=C-Ar and Fur-CH=C-respectively, because in the case of Fur-CH=C-there is a long range coupling with the furan-H and this evidence can be obtained from the coupling constants between H(7) and furan-H(9) as illustrated in Table 2. Further evidence to support our assignments was obtained from the 13 C NMR spectrum of compound (6b) that showed the carbons of the highly conjugated system at C(5) and C( 7) to be at δ 118.7 and 126.25 respectively as shown in Table 3.It is clear also from the 1 H NMR spectrum of the compounds (6a-d) that in the ClCH 2 CH 2 CO-system, the CH 2 adjacent to the carbonyl appears as a triplet at δ 3.722 ppm and the other CH 2 adjacent to the chlorine nuclei are completely decoupled from directly attached protons, and appear as two triplet signals at 2.54-2.77ppm, due to the strong electrical quadrupole moment effect [19].Another piece of evidence to support our assignment the structure of compound (6b) was obtained through MM2 calculations for the minimum and total steric energy, as illustrated in Figure 1.It is important to point out that we have examined steric energies from 68.479 kcal/mole to the lowest energy structure at 8..86 kcal/mole over 392 iterations.Minimization terminated normally because the gradient norm was less than the minimum gradient norm.

Experimental
General 1 H NMR spectra were recorded on Varian Plus 300 (300 MHz) or Bruker XL 300 (300 MHz) instruments, the 13 C NMR spectra (with DEPT 135) on a Bruker WP80 or XL 300 instrument.Infrared spectra listed as recorded 'neat' refer to a thin film of material on NaCl disks, and were taken on a Perkin Elmer 1600 FT-IR spectrometer.Mass spectra were recorded on a Kratos Concept instrument.Melting points were measured on an Electrothermal digital melting point apparatus and are uncorrected.The TLC analyses were carried out using Macherey-Nagel 0.25mm layer fluorescent UV 254 plates with the indicated solvent system.Elemental analyses were performed by M-H-W Laboratories (Phoenix, AZ) at University of Minho, Braga, Portugal.
α-Aracycl-β-(2-furyl)acrylic acid hydrazides (2a-d) [2] Hydrazine hydrate (1 mol) was added to a suspension of the 2-(3H)-furanones (1a-d) (1 mol) in absolute ethanol (20 mL).The reaction mixture was allowed to stand at room temperature with occasional shaking from time to time and then left overnight.The reaction was monitored by TLC and was shown to be complete after 2 days.Evaporation of the solvent by rotatory evaporator gave a colorless solid that was filtered off and recrystallized from a suitable solvent to give colorless crystals in 75-85% yield, as listed in Table 2.  (20 mL); after completion of the addition the solid was continue stirring for 1h, then filtered off and washed thoroughly with water.The product obtained was recrystallized from a suitable solvent as shown in Table 2.

4-Furylmethyl
To a solution of the α-aracycl-β-(2-furyl)acrylic acid hydrazides (2a-d) (1 mol) in benzene (50 mL) was added 3-chloro-propionyl chloride (3) (1.01 mol) and the mixture stirred at 0-15 o C for 5 h.The progress of the reaction was monitored by TLC and shown to be complete after 5-6 hrs and when the color become yellow.The solid separated out were collected and re-crystallized from ethanol to yield the title compounds in 80-92% yield (cf. Table 2).

6-Aryl-1-(3-chloropropanoyl)-4-[(E)-1-(2-furyl)methylidene)]-1,2,3,4-tetrahydro-3-pyridazinones (6a-d)
To a solution of the α-aracycl-β-(2-furyl)acrylic acid hydrazides (2a-d) (1 mol) in benzene (50 mL) was added 3-chloropropionyl chloride (3) (1.1 mol) and the reaction mixture was refluxed at 80 o C for 30-60 min.The progress of the reaction was monitored by TLC during this time and the reaction was shown to be complete after 1h when the color become yellow.The solvent was removed by rotatory evaporator and the solids which separated out were collected and then recrystallized from ethanol to yield the products in 80-92% yield (cf. Table 2).In a parallel experiment with hydrazine derivatives (4ad) in benzene solvent in the presence of acid catalyst (1.0 N HCl) using the same reaction conditions previously mentioned, the only products which could be identified by TLC after 30-60 min.were compounds (6a-d).These compounds were shown by direct comparison of m.p and mixed m.p, TLC and spectral data to be identical in all aspects with authentic samples.