Reaction of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione with some phosphorus halides: A simple synthesis of novel 1,2-benzoxaphosphinines

Abstract A simple method for design of some novel 1,2-benzoxaphosphinines 2–9, was achieved. The methodology depended on cyclization of 1-(2-hydroxy-phenyl)-3-phenylpropane-1,3-dione (1) as starting material with some phosphorus halides in dry solvent in the presence of a base. Reaction of the substrate 1 with some phosphorus halides, such as P,P-dichlorophenylphosphine, phenyl phosphonic dichloride, phenyl phosphorodichloridate, and phosphorus oxychloride in dry toluene containing triethylamine led to a predominant formation of 3-benzoyl-4-hydroxy-2H-1,2-benzoxaphosphinines 2–5, respectively. Under the same reaction conditions, the molecular structures of type 3-benzoyl-4H-1,2-benzoxaphosphinin-4-ones 6 and 7 were isolated by treatment of the substrate 1 with phosphorus pentachloride and phosphorus tribromide, respectively. In addition, the interesting 4-(1-phenyl-ethanoyl)-1,2,λ5-benzoxaphosphinines 8 and 9 were obtained by treatment of compound 1 with acetonyl and benzyl triphenylphosphonium chlorides, respectively, in dry dioxane and sodium hydride. The chemical structures of the title compounds were established by elemental analysis and spectral tools. Graphical Abstract


Results and discussion
The reaction of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (1) [30] with three types of phenyl phosphorus halides, namely dichlorophenylphosphine, phenyl phosphonic dichloride, and phenyl phosphorodichloridate in dry toluene containing triethylamine as a base, was studied. These reactions afforded the 3-benzoyl-4-hydroxy-2-phenyl-2H-1,2benzoxaphosphinine (2), 3-benzoyl-4-hydroxy-2-oxido-2-phenyl-2H-1,2-benzoxaphosphinine (3) and 3-benzoyl-4-hydroxy-2-oxido-2-phenyoxy-2H-1,2-benzoxaphosphinine (4), respectively, in moderate yields (Scheme 1). The moderate yields due to decreasing of electrophilicity character of the phosphorus atom in the used phosphorus halides as following: PhP(Cl 2 )¼O > PhOP(Cl 2 )¼O > PhPCl 2 . [31] These reactions started initially at 10 C for 30 min then heated for 8-12 h at 80-90 C. The plausible mechanism for these reactions was proposed by a nucleophilic attack of OH group in substrate 1 at the phosphorus atom of phosphorus dichloride reagents forming the salt A. By helping of triethylamine, the latter salt A was converted into the intermediate B. Upon heating of the mixture reaction, another nucleophilic attack was occurred by the negative charge of the activated methylene group at the phosphorus atom in the intermediate C. By releasing of the chloride anion, the intermediate C may give the cyclic intermediate D that was rearranged through keto-enol tautomerism into the isolated forms of the products 2-4 (Scheme 1). In this condensation, the formation of product 3 was selected as a model reaction to optimize the best reaction conditions. Toluene as a nonpolar solvent was found to be an ideal solvent (72% yield) than benzene (41% yield) and THF (45% yield) since the reactants readily dissolved in it. In addition, the boiling point of toluene is high (110 C) that gives the required energy for the reactions to complete in a suitable time. The use of triethylamine as aprotic base in toluene for these reactions is effective than other bases, such as pyridine (32% yield), 1-methylpiperidine (45% yield), and DBU (48% yield), which gave low yields. Triethylamine readily scavenges the liberated hydrogen chloride forming its salt and thereby drives the reaction to be completed.
On the other hand, the product 3 was also obtained through oxidation of compound 2 by hydrogen peroxide in dry tetrahydrofuran according to the reported method and mechanism in the literature (Scheme 2). [32,33] Structures of the synthesized compounds 2-4 were confirmed by elemental analysis and mass spectrometry as well as IR, 1 H-, 13 C-, and 31 P-NMR spectra. The infrared spectra showed absorption bands for OH stretching frequencies in the region 3390-3008 cm À1 . The carbonyl groups of products 2-4 exhibited absorption bands at 1660, 1687, and 1646 cm À1 , respectively, in a relatively low region than normal due to the effect of aromatic phenyl rings attached to them. [34] The 1 H-and 13 C-NMR spectra confirmed the absence of methylene group. However, the 1 H-NMR spectra displayed characteristic signals for OH groups at position 4 in the regions d 12.15-12.92 ppm. The aromatic protons appeared in the expected regions at d 6.90-8.18 ppm. The 13 C-NMR spectra for the products 2-4 recorded all the carbon atoms at the expected values. For example, the carbonyl carbon atoms were displayed at d 166.6-172.3 ppm. Further, the 31 P-NMR spectrum of compound 3 recorded a singlet at d 38.42 ppm. The EI mass spectra of compounds 2-4 were recorded and interpreted in support of the proposed structures.
The above-mentioned effective synthesis of novel 1,2-benzoxaphosphinine compounds motivated us to extend the scope of substrate 1 to react with other examples of phosphorus halides. Thus, reaction of substrate 1 with phosphorus oxychloride under the same reaction conditions gave 3-benzoyl-2,4-dihydroxy-2-oxido-2H-1,2-benzoxaphosphinine (5) (Scheme 3), whereas its treatment with phosphorus pentachloride led to the formation of 3-benzoyl-2,2-dichloro-4H-1,2k 5 -benzoxaphosphinin-4-one (6) (Scheme 3). The product 5 was also obtained by warming of compound 6 in aqueous sodium carbonate for 1 h (Scheme 3). Similarly, the reaction of phosphorus tribromide with Scheme 3. Reaction of the substrate 1 with POCl 3 , PCl 5 , and PBr 3 . compound 1 in dry toluene containing three equivalent amounts of triethylamine produced the interesting novel 3-benzoyl-4H-1,2-benzoxaphosphinin-4-one (7) in good yield (Scheme 3). The synthesis of both products 6 and 7 is similar to the above-mentioned products 2-4. The pathways suggested the cyclocondensation of the substrate 1 with the phosphorus halides by helping of triethylamine. Moreover, the product 5 was formed by spontaneously air hydrolysis of the nonisolable intermediate F or intended hydrolysis for the product 6, followed by rearrangement through keto-enol tautomerism (Scheme 3).
Structures of the latter products 5-7 were deduced by the spectral and analytical tools. For example, the IR spectrum of compound 7 showed two characteristic carbonyl groups at 1694 (benzoyl) and 1649 (C¼O) cm À1 . Its 1 H-NMR spectrum displayed multiplet signals for the aromatic protons between d 7.48 and 8.10 ppm, while its 31 P-NMR spectrum exhibited a singlet signal at d 210.02 ppm. Moreover, its 13 C-NMR spectrum revealed two specific signals at d 163.1 and 177.6 ppm for the two carbonyl groups. Furthermore, its molecular ion peak M þ was recorded at m/z 268 in the mass spectrometry.
reactants are more easily soluble in dioxane than in toluene, the yield products were higher. In addition, sodium hydride caused good yield than triethylamine. The plausible mechanism for the formation of both products 8 and 9 was predicted as removal of hydrogen halide by a nucleophilic attack of OH group in substrate 1 at the phosphorus atom of forming the nonisolable intermediate K. Then, the activated methylene -CH 2 P(Ph) 3 -in the intermediate L condensed with the carbonyl group with concomitant loss of a molecule of water through the intermediate M (Scheme 4). The IR spectra of both products 8 and 9 showed the characteristic C ¼ O benzoyl at 1702 and 1765 cm À1 , respectively. Their 1 H-NMR spectra displayed the aromatic protons as multiplets in the region d 6.97-8.18 ppm. Also, the CH 2 protons in both compounds were resonated as doublets at d 5.72 (J ¼ 16 Hz) and 5.22 (J ¼ 14.6 Hz) ppm, respectively, for their homotropic effect. [35] The 13 C-NMR spectra for both products displayed the aromatic carbons in the expected region. The CH 2 carbon atoms were observed as doublets at d 38.3 (J ¼ 58 Hz) and 50.0 (J ¼ 56 Hz) ppm. The C¼O benzoyl was observed around d 159.3 ppm. The C-3 carbon atom in each product which was directly linked to phosphorus atom appeared as a doublet in the region d 129.4-128.5 (J PC ¼ 86-85 Hz). The 31 P-NMR chemical shift of compound 9 appeared at d 24.31 ppm. Finally, the mass spectra of 8 and 9 supported their formation, although they did not show the molecular ion peaks, indicating the fragile nature of these compounds. Thus, the mass spectrum of 8 showed the highest value peak at m/z 463 (M þ -Ph, 7%), while product 9 recorded the highest peak at m/z 497 (M þ -Ph, 12%). [36] Experimental The melting points were determined in an open capillary tube on a digital Stuart SMP-3 apparatus. Infrared spectra were measured on FT-IR (Nicolet IS10) spectrophotometer using KBr disks. The 1 H-and 13 C-NMR spectra were measured on Gemini-300BB spectrometer (400 and 100 MHz), using DMSO-d 6 as a solvent and TMS (d) as an internal standard. 31 P-NMR spectra were measured on a Bruker (162 MHz) spectrophotometer using DMSO-d 6 as a solvent, TMS as an internal standard and 85% H 3 PO 4 as an external reference. Mass spectra were recorded on direct probe controller inlet part to single quadrupole mass analyzer in (Thermo-Scientific GCMS). Elemental microanalysis was performed Perkin-Elmer 2400II at the Chemical War department, Ministry of Defense. The purity of the synthesized compounds was checked by thin-layer chromatography (TLC) and elemental microanalysis.