Dihalooxygenation of Alkynes and Alkynols: Preparation of 2,2-Dihaloketones and gem-Dihalolactols

Nattawadee Chaisan; Sureeporn Ruengsangtongkul; Charnsak Thongsornkleeb; Jumreang Tummatorn; Somsak Ruchirawat

doi:10.1055/a-1774-7077

Synlett, Inhaltsverzeichnis

Synlett 2022; 33(14): 1426-1430
DOI: 10.1055/a-1774-7077

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Organic Chemistry in Thailand

Dihalooxygenation of Alkynes and Alkynols: Preparation of 2,2-Dihaloketones and gem-Dihalolactols

Nattawadee Chaisan

^aProgram on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

,

Sureeporn Ruengsangtongkul

^bLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

,

Charnsak Thongsornkleeb ∗

^aProgram on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

^bLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

,

Jumreang Tummatorn

^aProgram on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

^bLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

,

Somsak Ruchirawat

^aProgram on Chemical Biology, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

^bLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand

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Abstract

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Abstract

A mild and convenient method for the synthesis of 2,2-dihaloketones and gem-dihalolactols has been developed. For the synthesis of 2,2-dihaloketones, alkynes were employed as substrates to react with halogenating agents, Cl₂ or ClBr, that were generated in situ from aqueous HCl and NCS or NBS, respectively. On the other hand, gem-dihalolactols could be prepared from alkynol substrates by using the same reaction conditions. This method could be applied to a broad range of substrates to give the corresponding products in low to good yields.

Key words

dihaloketones - dihalolactols - alkynes - alkynols - halogenation

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Referenzen

References and Notes

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11 The results are summarized in the Supporting Information.
12 These were observable in their ¹H NMR spectra: 3w-Br/2w-Br = 88:12 and 3x-Br/2x-Br = 81:19; see the Supporting Information.
13 2,2-Dichloro-3-hydroxy-1-phenylpropan-1-one (2a-Cl); Typical Procedure NCS (193.3 mg, 1.448 mmol, 2.0 equiv) and 1 M aq HCl (0.38 mL, 0.38 mmol, 0.5 equiv) were added to a solution of alkynol 1a (95.8 mg, 0.725 mmol, 1.0 equiv) in 1,4-dioxane (3.6 mL), and the mixture was stirred at r.t. until the reaction was complete (TLC; typically 5 h). The mixture was then diluted with H₂O, and the separated aqueous phase was extracted with EtOAc (×3). The combined organic phases were washed with sat. aq NaCl then dried (Na₂SO₄), filtered, and concentrated to give a crude product. This was purified by column chromatography (silica gel, 10% EtOAc–hexane) to give a yellow oil; yield: 117.2 mg (74%). IR (neat): 2926, 1691, 1260, 688 cm^–1.¹H NMR (300 MHz, CDCl₃): δ = 8.33–8.29 (m, 2 H), 7.61 (tt, J = 7.5, 1.2 Hz, 1 H), 7.51–7.45 (m, 2 H), 4.27 (s, 2 H), 2.95(br s, 1 H). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 189.1, 134.1, 131.1, 131.0, 128.2, 83.6, 70.4. HRMS (ESI-TOF):m/z [M]^∙/+ calcd for C₉H₉ ³⁵Cl₂O₂: 218.9974; found: 218.9972.

Zusatzmaterial

Supporting Information