Deoxydichlorination of aldehydes catalyzed by Diphenyl sulfoxide Chimica Techno Acta LETTER published by Ural Federal University 2021, vol. 8(4), № 20218408 eISSN 2411-1414; chimicatechnoacta.ru DOI: 10.15826/chimtech.2021.8.4.08 1 of 4 Deoxydichlorination of aldehydes catalyzed by Diphenyl sulfoxide I.A. Gorbunova a, D.A. Shipilovskikh ab, S.A. Shipilovskikh ac* a: Perm State University, 614990, Perm, Russia b: Perm National Research Polytechnic University, 614990, Perm, Russia c: ITMO University, 197101, Saint Petersburg, Russia * Corresponding author: s.shipilovskikh@metalab.ifmo.ru This short communication (letter) belongs to the MOSM2021 Special Issue. © 2021, The Authors. This article is published in open access form under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Abstract The diphenyl sulfoxide-catalyzed conversion of aldehydes to 1,1-dichlorides is reported. The reaction proceeds via a sulfurous (IV)-catalysis manifold in which diphenyl sulfoxide turnover is achieved using oxalyl chloride as a consumable reagent. Keywords aldehydes Lewis base catalysis organocatalysis diphenyl sulfoxide Received: 31.10.2021 Revised: 17.11.2021 Accepted: 01.12.2021 Available online: 03.12.2021 1. Introduction Nucleophilic substitutions SN are general chemical trans- formations, as they allow, for example, strategic building of C–Cl, C–O, C–N and C–C bonds [1–10]. In addition, gem- inal dihalides, especially dichlorides, are important inter- mediates in chemical synthesis, and the traditional syn- thesis protocols are often limited in terms of cost efficien- cy and waste balance [11, 12]. However, research in this area is at an early stage in the study of such catalytic reac- tion. Although by now several effective protocols for the preparation of dichlorides from aldehydes catalyzed by a Lewis base have been disclosed [13, 14], all possibilities for studying these reactions have not yet been realized (Scheme 1). Dichlorides – important class of intermediates in organic synthesis. They were used for alkenylation of carbonyl compounds [15, 16], cyclopropanation and epoxidation [17–19], dimerization [20, 21] and others [22–25]. In addi- tion, geminal dichlorides are encountered as structural mo- tifs in polyhalogenated natural products [26, 27] (Fig. 1). 2. Experimental Yields are given for isolated products showing one spot on a TLC plate and no impurities detectable in the NMR spectrum. The identity of the products prepared by dif- ferent methods was checked by comparison of their NMR spectra. 1H and 13C NMR spectra were recorded at 400 MHz for 1H and 100 MHz for 13C NMR at room temperature; the chemical shifts (δ) were measured in ppm with respect to the solvent (CDCl3, 1Н: δ = 7.26 ppm, 13C: δ = 77.16 ppm; [D6] DMSO, 1Н: δ = 2.50 ppm, 13C: δ = 39.52 ppm). Cou- pling constants (J) are given in Hertz. Splitting patterns of apparent multiplets associated with an averaged coupling constants were designated as s (singlet), d (doublet), t (triplet), q (quartet), sept (septet), m (multiplet), dd (doublet of doublets) and br (broadened). Melting points were determined with a «Stuart SMP 30», the values are uncorrected. Flash chromatography was performed on silica gel Macherey Nagel (40–63 µm). Reaction progress was monitored by GC/MS analysis and thin layer chromatography (TLC) on aluminum backed plates with Merck Kiesel 60 F254 silica gel. The TLC plates were visualized either by UV radiation at a wavelength of 254 nm, or stained by exposure to a Dragendorff’s reagent or potassi- um permanganate aqueous solution. All the reactions were carried out using dried and freshly distilled solvent. 2.1. General method for synthesis of dichlorides from aldehyde Diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%) and aldehyde 1 (2 mmol, 1 equiv) were dis- solved in 15 mL of anhydrous toluene in a 25 mL round bottom flask equipped with a magnetic stirring bar. The resulting solution was treated dropwise with neat oxalyl chloride (0.26 mL, 3 mmol, 1.5 equiv (chlorine source)) http://chimicatechnoacta.ru/ https://doi.org/10.15826/chimtech.2021.8.4.08 http://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0002-8917-2583 Chimica Techno Acta 2021, vol. 8(4), № 20218408 LETTER 2 of 4 using an adjustable volume pipette (0.1–1.0 mL), followed by the temperature increase up to 100 °C; the mixture was stirred for 6 h. The reaction progress was monitored by GC-MS. After the reaction was complete, the solution was filtered and concentrated in vacuum. The crude mixture thus obtained was purified by flash chromatography on silica (petroleum ether/Et2O – 19/1). 2.1.1. (Dichloromethyl)benzene 4а Obtained from 1a (212 mg, 2 mmol), diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%), and ox- alyl chloride (0.26 mL, 3 mmol, 1.5 equiv), in anhydrous toluene (15 mL). Colorless oil (242 mg, 75%). 1H NMR (CDCl3, 400 MHz) δ (ppm): 6.75 (s, 1H, CH), 7.44 (m, 3H, HAr), 7.66 (m, 2H, HAr). 13C NMR (CDCl3, 100 MHz) δ (ppm): 72.0, 126.2, 128.8, 123.0, 140.4. 2.1.2. 1-(Dichloromethyl)-4-methylbenzene 4b Obtained from 1b (240 mg, 2 mmol), diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%), and ox- alyl chloride (0.26 mL, 3 mmol, 1.5 equiv), in anhydrous toluene (15 mL). Colorless oil (278 mg, 80%). 1H NMR (CDCl3, 400 MHz) δ (ppm): 2.40 (s, 3H, CH3), 6.68 (s, 1H, CH), 7.23 (m, 2H, HAr), 7.48 (m, 2H, HAr). 13C NMR (CDCl3, 100 MHz) δ (ppm): 21.7, 71.6, 126.1, 129.3, 137.5, 140.9. 2.1.3. 1-Bromo-4-(dichloromethyl)benzene 4с Obtained from 1с (370 mg, 2 mmol), diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%), and ox- alyl chloride (0.26 mL, 3 mmol, 1.5 equiv), in anhydrous toluene (15 mL). Colorless oil (345 mg, 72%). 1H NMR (CDCl3, 400 MHz) δ (ppm): 6.68 (s, 1H, CH), 7.46 (m, 2H, HAr), 7.55 (m, 2H, HAr). 13C NMR (CDCl3, 100 MHz) δ (ppm): 72.0, 124.3, 128.0, 131.9, 139.4. 2.1.4. 1-(Dichloromethyl)-4-nitrobenzene 4d Obtained from 1d (302 mg, 2 mmol), diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%), and ox- alyl chloride (0.26 mL, 3 mmol, 1.5 equiv), in anhydrous toluene (15 mL). Colorless oil (259 mg, 63%). 1H NMR (CDCl3, 400 MHz) δ (ppm): 6.78 (s, 1H, CH), 7.78 (m, 2H, HAr), 8.29 (m, 2H, HAr). 13C NMR (CDCl3, 100 MHz) δ (ppm): 70.2, 124.5, 127.9, 146.6, 149.2. 2.1.5. (E)-(3,3-Dichloroprop-1-en-1-yl)benzene 4e Obtained from 1e (264 mg, 2 mmol), diphenyl sulfoxide (Ph2SO) (40 mg, 0.2 mmol, 0.1 equiv, 10 mol.%), and ox- alyl chloride (0.26 mL, 3 mmol, 1.5 equiv), in anhydrous toluene (15 mL). Colorless oil (286 mg, 77%). 1H NMR (CDCl3, 400 MHz) δ (ppm): 6.34 (d, J = 7.6 Hz, 1H, CH), 6.39 (dd, J = 14.7 and 7.6 Hz, 1H, CH), 6.72 (d, J = 14.7 Hz, 1H, CH), 7.41 (m, 5H, HAr). 13C NMR (CDCl3, 100 MHz) δ (ppm): 73.5, 127.0, 128.2, 129.1, 129.3, 132.5, 134.9. Scheme 1 Deoxydichlorination of aldehydes to 1,1-dichlorides Fig. 1 Natural products including a fragment of dichlorides Chimica Techno Acta 2021, vol. 8(4), № 20218408 LETTER 3 of 4 3. Results and discussion The investigation commenced with establishing the best conditions for the deoxydichlorination of aldehydes, employing benzaldehyde 1a as a model substrate (Scheme 2). First, the role of each reagent was evaluat- ed. Oxalyl chloride on its own did not produce (Di- chloromethyl)benzene 4a (Table 1, entry 1). The use of stoichiometric quantities of Ph2SO and (COCl)2 in ace- tonitrile resulted in low conversion of 1a into 4a (en- try 2). With 10 mol.% Ph2SO and 1 equiv of oxalyl chlo- ride, 4a was formed in 15% conversion (entry 3), which increased to 51% after change the solvent on toluene (entry 4). The up of the temperature to 100 °C and use 1.5 equiv of oxalyl chloride to give the best results of conversion to 92% (entry 11). Scheme 2 The reaction for optimization of the conditions Table 1 Optimization of the reaction conditions Entry Equiv of (COCl)2 Ph2SO, mol.% Solvent T, °C t, h Conv., %b 1 1 – MeCN 50 1 0 2 1 100 MeCN 50 1 19 3 1 10 MeCN 50 6 15 4 1 10 Tol 50 6 53 5 1 10 DCM 40 6 10 6 1 10 DCE 50 6 18 7 1 10 THF 50 6 37 8 1 10 Et2O 30 6 4 9 1 10 Tol 100 6 85 10 1 10 Tol 100 12 88 11 1.5 10 Tol 100 6 92 aGeneral conditions: 1a (0.2 mmol), Ph2SO, dry solvent (1 mL), dropwise addition of neat (COCl)2. The reactions were carried out for 1–12 h before an aliquot (50 μL) was taken, quenched with aqueous solvent (1 mL), and analyzed by GC. bConversion to 4a was calculated from GC. The substrate scope was investigated next. As shown in Scheme 3, the reaction work well with different type of aromatic aldehydes, including donor and acceptor substit- uents at the fourth position of the ring. The use of cin- namaldehyde under the reaction conditions also showed good results. The proposed mechanism is depicted in Scheme 4. We think that the catalytic cycle start with quick for- mation of the intermediate chlorodiphenylsulfonium chloride (B) upon treatment of diphenyl sulfoxide (A) with (COCl)2. Previously, a similar process was carried out by Denton with triphenylphosphine oxide as a cata- lyst [14]. Next, in the catalytic cycle, the intermediate B reacts with the aldehyde 1 via oxygen to form the in- termediate C, which then undergoes elimination to fur- nish the geminal dichloride 4 and regenerate the cata- lyst A. Scheme 3 Deoxydichlorination of aldehydes catalyzed by Diphenyl sulfoxide Scheme 4 Proposed mechanism 4. Conclusions We have developed a highly expedient protocol for a cata- lytic deoxydichlorination of aldehydes under conditions of a catalytic Swern Oxidation catalyzed by diphenyl sulfox- ide. The salient features of the method are: (i) operational simplicity, (ii) low catalyst loading (10 mol.%), (iii) medi- um reaction times and (iv) mild conditions. Acknowledgments The authors thank Russian Science Foundation for grant 20-73-00081. Chimica Techno Acta 2021, vol. 8(4), № 20218408 LETTER 4 of 4 References 1. Huy PH. Lewis base catalysis promoted nucleophilic substitu- tions – recent advances and future directions. Eur J Org Chem. 2020;(1):10–27. doi:10.1002/ejoc.201901495 2. Beddoe RH, Sneddon HF, Denton RM. The catalytic Mitsunobu reaction: a critical analysis of the current state-of-the-art. Org Biomol Chem. 2018;16(42):7774–7781. doi:10.1039/C8OB01929K 3. Shipilovskikh SA, Rubtsov AE. Dehydration of oxime to ni- triles. AIP Conf Proc. 2019;2063:030019. doi:10.1063/1.5087327 4. 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