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Synlett 2022; 33(14): 1426-1430
DOI: 10.1055/a-1774-7077
DOI: 10.1055/a-1774-7077
cluster
Organic Chemistry in Thailand
Dihalooxygenation of Alkynes and Alkynols: Preparation of 2,2-Dihaloketones and gem-Dihalolactols
This research project was supported by the Thailand Research Fund (TRF; RSA6180045 for C.T.), the Thailand Science Research and Innovation (TSRI) for Chulabhorn Research Institute (Grant No. 313/2220) and for Chulabhorn Graduate Institute, Chulabhorn Royal Academy (FFB640035 Project Code 50171). This research was also supported in part by the grant from Center of Excellence on Environmental Health and Toxicology (EHT), OPS, Ministry of Higher Education, Science, Research and Innovation. NC was also grateful for the support from the Royal Golden Jubilee (RGJ) scholarship program (PHD/0139/2560).
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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1774-7077.
- Supporting Information
Publication History
Received: 23 January 2022
Accepted after revision: 17 February 2022
Accepted Manuscript online:
17 February 2022
Article published online:
15 March 2022
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- 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.