Synthesis of 4-Aryl-3,4-dihydro- and 2,4-Diaryl-2,3,3a,4-tetrahydrochromeno[3,4-d][1,2,3]diazaphospholes

Abstract

Reaction of 2-arylchromone-4-semicarbazones with POCl₃ in the presence of SOCl₂, followed by treatment with EtOH or MeOH gave 4-aryl-3,4-dihydrochromeno[3,4-d][1,2,3]diazaphospholes. Likewise, 2,4-diaryl-2,3,3a,4-tetrahydro-chromeno[3,4-d][1,2,3]diazaphospholes were obtained from 2-­phenylchromone-4-arylhydrazones.

Key words

dihydrochromeno[3,4-d][1,2,3]diazaphosphole - tetra­hydrochromeno[3,4-d][1,2,3]diazaphosphole - synthesis - X-ray crystal structure

References and Notes

• 1 Ying H. Hu Y. He Q. Li R. Yang B. Eur. J. Med. Chem.  2007,  226 
• 2 Luber J. Schmidpeter A. Angew. Chem.  1976,  88:  91 
• 3 Weinmaier JH. Luber J. Schmidpeter A. Pohl S. Angew. Chem.  1979,  91:  442 
• 4 Baccolini G. Dalpozzo R. Errani E. Tetrahedron  1987,  43:  2755 
• 5 Baccolini G. J. Chem. Soc., Perkin Trans. 1  1989,  1053 
• 6 Chen R. Cai B. Li G. Synthesis  1991,  783 
• 7 Chen R. Cai B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  57:  83 
• 8 Chen R. Cai B. Liu L. He L. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  56:  129 
• 9 Baccolini G. Sgarabotto P. J. Chem. Soc., Chem. Commun.  1991,  34 
• 10 Chaikovskaya AA. Kudrya TN. Lakhtadir AI. Smaliy RV. Pinchuk AM. Tolmachev AA. Heteroat. Chem.  2005,  16:  81 

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General Procedure for 4-Aryl-3,4-dihydrochrom-eno[3,4- d ][1,2,3]diazaphospholes 2a-n and 2,4-Diaryl-2,3,3a,4-tetrahydrochromeno[3,4- d ][1,2,3]diazaphos-pholes 4a-k
Method A: A mixture of the 2-phenylchromone-4-semicarbazone (1, 10 mmol; or 3 for preparation of 4), POCl₃ (6 mL), and SOCl₂ (0.6 mL) was heated to 80 °C quickly, and the reaction mixture was held for 60 min (or 40 min for 4). Then the excess POCl₃ and SOCl₂ were evaporated in vacuo. Corresponding alcohol (6 mL) was added into the residue and refluxed for 30 min, and then the solution was concentrated. The residue was diluted with H₂O (20 mL) and extracted thoroughly with CH₂Cl₂ (3 × 8 mL). The organic layer was combined and washed with brine (2 × 8 mL), dried over anhyd Na₂SO₄, and concentrated in vacuo to give crude product, which was further purified by column chromatography (silica gel, using different ratio of EtOAc-PE as eluent according to different products).
Method B: A mixture of the 2-phenylchromone-4-semi-carbazone (1, 10 mmol), POCl₃ (6 mL), and SOCl₂ (0.6 mL) was stirred at r.t. under a nitrogen atmosphere for 24 h. Then the excess POCl₃ and SOCl₂ were evaporated in vacuo. Corresponding alcohol (6 mL) was added into the residue and heated to reflux for 30 min, and then the solution was concentrated in vacuo. The obtained residue was treated in the same manner as method A.

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All compounds gave satisfactory analytical and spectral data. Data for selected compounds are as follows:
Compound 2a (Table [1] , entry 2): white crystal, mp 98-100 °C (EtOAc-PE). ¹H NMR (400 MHz, CDCl₃): δ = 8.19 (dd, 1 H, J = 7.6, 1.6 Hz, H-9), 7.45-7.41 (m, 5 H, H-2′, 3′, 4′, 5′, and 6′), 7.34 (td, 1 H, J = 7.6, 1.6 Hz, H-8), 7.17 (t, 1 H, J = 7.6 Hz, H-7), 7.07 (d, 1 H, J = 7.6 Hz, H-6), 6.68 (s, 1 H, H-4). ¹³C NMR (100 MHz, CDCl₃): δ = 154.3, 152.4, 144.7, 138.8, 131.1, 129.7, 129.1, 126.8, 124.3, 122.9, 117.1, 117.0, 77.0. ³¹P NMR (600 MHz, CDCl₃): δ =
-104.71. MS (ESI): m/z = 267 [M + 1]⁺. Anal. Calcd (%) for C₁₅H₁₁N₂OP (266.2): C, 67.67; H, 4.16; N, 10.52. Found: C, 67.87; H, 4.05; N, 10.66.
Compound 4a (Table [3] , entry 1): orange crystal, mp 154-156 °C (EtOAc-PE). ¹H NMR (400 MHz, CDCl₃): δ = 8.31-8.30 (m, 1 H, H-3′′), 8.10 (dd, 1 H, J = 9.2, 2.4 Hz, H-9), 8.06 (dt, 1 H, J = 8.4, 1.6 Hz, H-5′′), 7.71-7.69 (m, 1 H, H-6′′), 7.67-7.62 (m, 2 H, H-2′ and 6′), 7.48-7.37 (m, 3 H, H-8, 3′, and 5), 7.20-7.13 (m, 2 H, H-6 and 7), 3.46-3.26 (m, 3 H, OCH ₂ CH₃), 2.96-2.89 (m, 1 H, OCH ₂ CH₃), 0.94 (t, 3 H, J = 7.2 Hz, OCH₂CH ₃ ), 0.90 (t, 3 H, J = 7.2 Hz, OCH₂CH ₃ ). ¹³C NMR (100 MHz, CDCl₃): δ = 151.8, 150.4, 146.4, 143.7, 137.2, 135.8, 135.3, 132.0, 128.3, 128.0, 126.7, 126.3, 126.1, 124.0, 122.9, 122.7, 122.4, 117.9, 114.5, 107.1, 102.1, 59.6, 59.5, 14.8, 14.4. ³¹P NMR (600 MHz, CDCl₃): δ = -18.86. MS (ESI): m/z = 546 [M + 1]⁺. Anal. Calcd (%) for C₂₅H₂₂Cl₂N₃O₅P (546.3): C, 54.96; H, 4.06; N, 7.69. Found: C, 55.12; H, 3.97; N, 7.54.

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Crystal structure analysis of 4a: C₂₅H₂₂Cl₂N₃O₅P, M = 546.34, yellow prism (0.47 × 0.30 × 0.27 mm³), triclinic, space group P1, a = 9.1549(3), b = 10.7168(4), c = 17.6272(6) Å, α = 102.9363(12), β = 90.2713(9), γ = 117.4265(10)°, V = 1484.41(9) ų, λ (Mo Kα) = 0.71075 Å and F(000) = 658, the final R = 0.0687 and wR = 0.2066 for 4943 observed reflections [I > 2σ(I)]. The crystallographic data has been deposited at the Cambridge Crystallographic Data Centre with deposition no. CCDC 645475.