Reactivity of some structural analogs of dehydroacetic acid with o -phenylenediamine

4-Hydroxy-6-methyl-3-(3-arylpropanoyl)-2 H -pyran-2-ones 14a-c and 4-hydroxy-6-methyl-3-(5-phenylpentanoyl)-2 H -pyran-2-one 15 , which are structural analogs of dehydroacetic acid (DHA) 1 , react with o -phenylenediamine 2 according to the solvents and reaction conditions. New heterocyclic compounds have been obtained and characterized


Results and Discussion
The electron impact mass spectra (EI MS) showed the addition of one molecule of hydrogen to the compound 12c and two molecules of hydrogen to the compound 13.The 1 H NMR spectra showed the existence of two methylenes -CH2in the structure of 14c and four methylenes -CH2-in the structure of 15.The 1 H NMR spectra of the compounds 14c and 15 also presented the signals at 16.56 ppm and at 16.10 ppm, respectively.These signals assigned to proton H-O at the site 4 of the pyrone ring.The position of H-O in the structures of 12c and 13 has been confirmed by HMBC spectrum which showed their connectivities with C-3, C-4 and C-5 of the pyrone ring (Figure 1).
The study of the reactivity of the compounds 13a-c and 14 with o-PDA 2 was achieved in ethanol and in toluene as solvents under several reaction conditions.
We reacted compounds 14a-c and 15 with o-PDA 2 in ethanol at room temperature for 6 hours (procedure A), under thermal refluxing for 30 minutes (procedure B) and under MW irradiation at 100 °C during 1 minutes (procedure C) and 4 minutes (procedure D).
For the first three procedures (A, B and C), the same products 16a-c and 17 were separated for the four chosen cases.The best yields were obtained at room temperature (procedure A) (Scheme 3).For the procedure using MW irradiation for 4 minutes (procedure D) the behaviour of 14a-c and 15 with o-PDA 2 was very different.The four compounds give the same product 18 (Scheme 3) with departure of one molecule of water and a molecule of alkylbenzene.We notes that the temperature of the mixture at the end of the reaction for the procedure C was 77 -78 °C, whereas the temperature of the mixture at the end of the reaction for the procedure D was 89-92 °C.
We have prolonged the agitation at room temperature for one week and the refluxing thermal for 24 hours, but we did not succeed in obtaining the compound 18; it was always the derivatives 16a-c and 17 which were formed.
Compound 18 was also obtained from 16a-c and 17 in ethanol, under MW irradiation at 100 W for 4 min.
The EI MS of 16a-c and 17 confirmed the condensation of only one molecule of o-PDA with loss of one molecule of water during the reaction.The 1 H NMR spectra showed a signal at 3.70-3.82ppm attributed to two equivalent protons where HSQC experiment confirmed that these two protons are carried by an heteroatom, which can be only a nitrogen atom. 1 H NMR spectra showed the signals at 5.72 ppm and at 2.22 ppm, assigned to the protons H-C5 of the pyrone ring and H-C7 of the methyl, respectively.The 1 H NMR spectra also showed a signal at 15.30 ppm.Originally, we considered a structure analogous to the compound 3, but the HMBC experiment showed some connectivities between this signal at 15.30 ppm and the three signals of the carbons C-3, C-3' and the C-4', which confirmed that this proton is not carried by the oxygen atom at the site 4, but it is carried by the nitrogen atom at the site 3' (Figure 1), where the derivatives 15a-c and 16 were obtained.
The hydrolysis reaction of 15a-c and 16 in HCl: 1N under thermal refluxing for 1 hour or under MW irradiation at 100 W for 3 minutes permitted the recuperation of 13a-c and 14 with o-PDA 2 (Scheme 3).
The EI MS of the compound 18 showed the condensation of only one molecule of o-PDA 2 with loss of one molecule of water and a molecule of alkylbenzene by the observation of the molecular peak at 242(80%), where the molecular formula C13H10N2O3 was confirmed.
The 1 H NMR spectra confirmed the structure of the compound 18 by the observation of two signals at 2.15 ppm and at 5.83 ppm assigned to the protons H-C7 of the methyl and H-C5 of the pyrone ring, respectively.The 1 H NMR spectra showed also two doublets of doublets in the domain of the aromatic protons at 7.32 ppm and at 7.75 ppm, each one of them assigned to two protons of the aromatic ring in symmetry, which is in perfect accord with the 13 C NMR spectra data, where the presence of two intense signals, each one of them represented two carbons (C5', C8') and (C6', C7') of the aromatic ring in symmetry.These data were confirmed by HSQC experiment.The 1 H NMR spectra showed a signal centered on 13.15 ppm represented the sum of two protons, which is assigned to the two protons H-N in symmetry.The position of these protons was confirmed by an HMBC experiment (Figure 1).In toluene, under thermal refluxing for 3 hours or under MW irradiation at 200 W for 4 minutes, we could separate two products from every compound 13a-c and 14 with o-PDA 2. The first product is the same for the four reactions.It was separated by filtration ebullition (111 °C).Its spectroscopic data revealed that it was the TAL 9.
After the cooling of every filtrate and filtration, the second products 19a-c or 20 were separated (Scheme 4).from15) 87 (from15) Procedure A: reaction mixture steered at rt for 6h, solvent: ethanol.Procedure B: reaction mixture submitted to the thermal reflux for 1h, solvent: ethanol.Procedure C: reaction mixture submitted to the MW irradiation for 1min, solvent: ethanol.Procedure D: reaction mixture submitted to the MW irradiation at 100 W for 4min, solvent: ethanol.Procedure E: reaction mixture submitted to the thermal reflux for 3h, solvent: toluene.Procedure F: reaction mixture submitted to the MW irradiation at 200 W for 4min, solvent: toluene.

Conclusions
The study of the reactivity of the compounds 14a-c and 15, analogs of the DHA 1, with o-PDA 2 permitted the synthesis some new heterocyclic compounds.The compounds 14a-c and 15 with o-PDA 2 react according to the reaction conditions.In ethanol, under thermal refluxing, under agitation at room temperature or under MW irradiation at 100 W for 1 minute we obtained 16a-c and 17.However, under MW irradiation at 100 W for 4 minutes, we obtained the product 18.In toluene, under thermal refluxing or under MW irradiation at 200 W, we have achieved an important reaction of deacylation, where we have separated the TAL 9 and 2arylalkylbenzimidazoles compounds 19a-c and 20 with good yields.

Experimental Section
General.The catalytic reductions of 12a-c and 13 were carried out in a quick closure autoclave (Prolabo).The reactions were carried out in a microwave oven dedicated to organic synthesis (Milestone, Lab Terminal 800 controller) at P=1 bar.Melting points were determined on a Stuart scientific SPM3 apparatus fitted with a microscope and are uncorrected. 1H and 13 C NMR spectra were recorded on a Bruker DRX 300 spectrometer, operating at 300.13 and 75.47 MHz, respectively; the chemical shifts are expressed in  (ppm) and coupling constants (J) in (Hz). 1 H and 13 C NMR assignments were made using HSQC and HMBC experiments.Electron impact mass spectra (EI MS) were obtained at 70 eV electron impact ionisation using Nermag R 10-10C Quadruple mass spectrometer.Infrared spectra were recorded on Magna-IR 550 series II Nicolet apparatus, using potassium bromide pellets.UV spectra were recorded on Cary 50 Scan UV-Visible spectrometer in acetonitrile and elemental analyses CHN performed with a Perkin-Elmer 2400 series II CHNO/S at the Scientific and Technical Research Center in Physical and Chemical Analyses (C.R.A.P.C), Algiers, Algeria.The compounds 12a-c and 13 were prepared by following the literature. 11The compounds 14a-b were obtained according to the method described in literature, 10 which is the same synthesis method used for 14c and 15.The yields of all compounds are reported in Table 1.preparation 3-[3-(3,4 A mixture of 12c (6.52, 20 mmol) or 13 (5.64,20 mmol) with 10% of its weight of Pd/C:10% in ethyl acetate (50 ml) was introduced in autoclave under pressure 11Kg/cm 2 of hydrogen H2 for 24 h at rt.After filtration and evaporation of solvent, the resultant was crystallized from ethanol.

General method for preparation (3E
Scheme 1

Scheme 3 .
Scheme 3.Procedure A: at rt for 6 h; Procedure B: thermal refluxing for 1 h; Procedure C: MW irradiation at 100 W for 1 min; Procedure D: MW irradiation at 100 W for 4 min.

Scheme 4 .
Scheme 4. Procedure A: at rt for 6 h; Procedure B: thermal refluxing for 1 h; Procedure C: MW irradiation at 100 W for 1 min; Procedure D: MW irradiation at 100 W for 4 min; Procedure E: thermal refluxing for 3 h; Procedure F: MW irradiation at 200 W for 4 min.

Table 1 .
Procedures and physical data of the products 16a