4-(diphenylphosphoryl)-1-phenylbutane-1,3-dione

1. Introduction

Phosphine oxides with an additional functional group are effective ligands for preparing complexes with lanthanides [1] with promising photophysical properties for fabricating OLEDs [2,3,4] or detecting various compounds [5]. Another class of well-studied ligands for complex synthesis with lanthanides are β-diketones [6]. Their functionalization with more coordination groups of various nature leads to more complex ligands with interesting and perspective coordination properties [7,8]. Moreover, both phosphine oxides and β-diketones are used as co-ligands for obtaining various luminescent complexes with lanthanides [9,10] for biomedical application [11]

We report here the synthesis and keto-enolic tautomerism of 4-(diphenylphosphoryl)-1-phenylbutane-1,3-dione.

2. Results and Discussion

The synthesis was performed based on acetophenone 1 by the technique described for enamines of acetoacetic acid (Scheme 1). [12]. By condensing 1 with ethyl acetate, diketone 2 was obtained [13]. Then diketone 2 was transformed in enamine 3 at the reaction with pyrrolidine [14]. The subsequent reaction with diphenylchlorophosphine intermediately forming phosphine 5 followed by oxidation and hydrolysis have led to the target phosphine oxide with a 50% yield. Synthesis of compound 1 at the reaction of 1-(diphenylphosphoryl)propan-2-one with methyl benzoate over lithium diisopropylamide is mentioned in the recent study of [15] as an intermediate. However, phosphine oxide 1 was not isolated, and its spectral characteristics were not defined either. Moreover, the synthetic route presented herein is distinguished by using simpler techniques and readily available reagents.

Structure of compound 1 was studied by ¹H NMR and ¹³C spectroscopy (Figure 1).

It is common knowledge that keto-enol tautomerism is characteristic of β-diketones and enol tautomer is often preferable in non-hydrogen bonding solvents [6,7,8,16]. In contrast, phosphine oxide 1 was isolated as a mixture of tautomers with prevailing diketo-form, the content of which as about 80% (Scheme 2). Mono-enol tautomers 1.1 and 1.2 made 8 and 12 %, respectively. Doublet H⁴ at 3.64 ppm (²J_PH = 14.5 Hz) and the H² proton singlet at 3.55 ppm confirm the presence of tautomer 1 as the main one in the mixture. At the same time, the H⁴ protons of minor tautomers 1.1 and 1.2, as well, show as doublets in the ¹H NMR spectrum (3.36 ppm, ²J_PH = 14.7 Hz and 3.14 ppm, ²J_PH = 14.5 Hz). Presence of the H⁴ proton doublets in alpha-position relative to phosphorus points clearly to the absence of any prototropism involving them. Signals of the H² protons located in tautomers 1.1 and 1.2 at the sp²-hybrid carbon atom manifest themselves in weaker fields (6.07 ppm, ⁴J_PH = 1.7 Hz, and 4.99 ppm, ⁴J_PH = 2.9 Hz). Protons of the hydroxy groups of enols 1.1 and 1.2 were not registered in the spectra, probably due to low intensity or deuterium exchange with CDCl₃ (For full ¹H NMR spectrum (0-18.2 ppm), please see ESI). Tautomers 1.3 and 1.4 were not registered spectrally. Thus, three of five possible tautomers are realized for compound 1.

4. Materials and Methods

All reagents were used as purchased from Sigma-Aldrich or Acros Chemicals without further purification. Solvents were purified by standard procedures before use. All reactions were run under an argon atmosphere unless in aqueous media.

NMR experiments were carried out with 400 MHz [400 MHz (¹H), 162 MHz (³¹P)] or 600 MHz [600 MHz (¹H), 243 MHz (³¹P),] spectrometers equipped with a pulsed gradient unit capable of producing magnetic field pulse gradients in the z-direction of 53.5 G cm^–1. All spectra were acquired in a 5 mm gradient inverse broadband probe head. Chemical shifts (d) are expressed in parts per million, relative to the residual ¹H signal of CDCl₃, and the signals are designated as follows: s, singlet; d, doublet; t, triplet; m, multiplet. Coupling constants (J) are in hertz (Hz). The ESI MS measurements were performed using an AmazonX ion trap mass spectrometer (Bruker Daltonic GmbH, Germany) in the positive or negative mode in the mass range of 70–3000. IR spectra were recorded with a Bruker Tensor-27 instrument for the samples in KBr pellets. The elemental analysis was carried out on a CHNS analyzer EuroEA3028-HT-OM (Eurovector SpA, Italy). The samples were weighed on Sartorius CP2P (Germany) microbalances in tin capsules. Callidus 4.1 software was used to perform quantitative measurements and evaluate the data received.

1-phenylbutane-1,3-dione (2)

Prepared according to the previously described procedure [13]. Yellow oil. Yield 85%. Exists as a mixture of keto/enol tautomers with 1:10 ratio. ¹H NMR (400 MHz, CDCl₃) (enol tautomer) δ 7.90 – 7.86 (m, 2H), 7.55 – 7.49 (m, 1H), 7.45 (dd, J = 8.3, 6.7 Hz, 2H), 6.18 (s, 1H), 2.20 (s, 3H).

1-phenyl-3-(pyrrolidin-1-yl)but-2-en-1-one (3)

Prepared by previously described procedure [14] from 1g (6.2 mmol) of 2 and 0.5 ml (0.44 g, 6.2 mmol) of pyrrolidine in 10 ml of benzene. Yiled 1.257g (94 %), brown oil, which solidifies while standing. Spectral data are in consistent with the previously described [17] ¹H NMR (600 MHz, CDCl₃) δ 7.86 (dd, J = 8.0, 1.6 Hz, 2H), 7.42 – 7.37 (m, 3H), 5.61 (s, 1H), 3.53 (brs, 2H), 3.37 (brs, 2H), 2.68 (s, 3H), 2.00 (brs, 4H). Compound 3 was used in the next step without purification.

4-(diphenylphosphoryl)-1-phenylbutane-1,3-dione (diketo-tautomer)

To a stirred solution of compound 3 (0.65 g, 3 mmol) and triethylamine (4.16 ml, 0.303 g, 3 mmol) in CH₂Cl₂ (5 ml) under an argon atmosphere Ph₂PCl (0.55 ml, 0.661 g, 3 mmol) was added dropwise and stirred at room temperature for 24 h. Then (NH₂)₂CO·H₂O₂ (0.282 g, 3 mmol) was added in one portion and the mixture stirred for additional 1 h. The reaction mixture was washed with water and 10 ml of 5% HCl solution was added. After 2d the water was separated, and organic phase was dried under Na₂SO₄ and concentrated on rotary evaporator. Crude product was purified by dry-column flash chromatography on Schott’s funnel (silica gel 230-400 mesh), using gradient elution (eluent from EtOAc : Hexane 4 :1 to EtOAc). Yield 0.542 g (50%)/ Pale yellow gum. Exists as a mixture of keto/enol tautomers 1, 1.1 and 1.2 with 20:3:2 ratio respectively. IR (thin film) 3434 (s, br), 2924 (w, sh), 1710 (w), 1603 (s, br), 1439 (s), 1224 (w), 1194 (s), 1116 (m), 1101 (m), 720 (m), 692 (s), 521 (s) cm ¹H NMR (400 MHz, CDCl₃) δ 7.74 – 7.71 (m, 3H, ArH), 7.71 – 7.67 (m, 3H, ArH), 7.55 – 7.47 (m, 3H, ArH), 7.47 – 7.39 (m, 6H, ArH), 6.21 (d, J = 1.6 Hz, 1H, H² of tautomer 1.1), 5.13 (d, J = 3.0 Hz, 1H, H² of tautomer 1.2), 3.78 (d, J = 14.6 Hz, 2H, H⁴), 3.69 (s, 2H, H²), 3.50 (d, J = 14.7 Hz, 2H, H⁴ of tautomer 1.1), 3.28 (d, J = 14.5 Hz, 2H, H⁴ of tautomer 1.1). ¹³C NMR (101 MHz, CDCl₃) δ 195.85 (d, J = 5.6 Hz), 167.02, 140.37, 132.48 (overlapped on the next signal), 132.47 (d, J = 2.9 Hz), 131.89, 131.38 (d, J = 104.0 Hz), 131.12, 130.87 (d, J = 10.0 Hz), 128.86 (d, J = 12.5 Hz), 128.86 (overlapped on the previous signal) 50.83, 46.88 (d, J = 56.5 Hz). ³¹P NMR (243 MHz, CDCl₃) δ 30.41 (1.1), 29.30 (1), 27.07 (1.2). Anal. Calcd for C₂₂H₁₉O₃P (%): C, 72.92; H, 5.29; P, 8.55 . Found (%): C 72.63; H 5.41; P 8.47. ESI-MS m/z = 363.17 [M + H]⁺