Product Selectivity Control under Acidic and Basic Conditions on Oxidative Transformation of 1,3-Dicarbonyls Using Sodium Hypochlorite Pentahydrate

Abstract

In this study, we reported that the reactivity of 1,3-dicarbonyls with sodium hypochlorite pentahydrate (NaOCl·5H₂O) as an easy-to-handle oxidant, alters greatly depending on the pH value. The reaction of NaOCl·5H₂O under weakly basic conditions (pH 12) gives the corresponding carboxylic acids in up to 97% yield. Upon addition of AcOH (pH 5), chlorination of active methylene sites proceeds efficiently to afford dichlorinated products in high yields.

Key words

1,3-dicarbonyls - sodium hypochlorite pentahydrate - cleavage - dichlorination - selective oxidation

Publication History

Received: 20 December 2023

Accepted after revision: 02 February 2024

Accepted Manuscript online:
02 February 2024

Article published online:
20 February 2024

• References

• 1a Podolesov B. J. Org. Chem. 1984; 49: 2644
• 1b Stepovik LP, Gulenova MV, Kalacheva IA, Potkina AY. Russ. J. Gen. Chem. 2011; 81: 550
• 1c Zhang Y, Jiao J, Flowers RA. J. Org. Chem. 2006; 71: 4516
• 2a Ramasubramanian R, Anandababu K, Kumar M, Mayilmurugan R. Dalton Trans. 2018; 47: 4049
• 2b Wang XY, Shang ZP, Zha GF, Chea XQ, Bukhari SN. A, Qin HL. Tetrahedron Lett. 2016; 57: 5628
• 2c Tachikawa Y, Cui L, Matsusaki Y, Tada N, Miura T, Itoh A. Tetrahedron Lett. 2013; 54: 6218
• 2d Tada N, Shomura M, Cui L, Nobuta T, Miura T, Itoh A. Synlett 2011; 2896
• 3a Duan X, Zhou H, Tian X, Liu J, Ma J. Synthesis 2015; 47: 777
• 3b Pu X, Li Q, Lu Z, Yang X. Eur. J. Org. Chem. 2016; 5937
• 3c Giannopoulos V, Katsoulakis N, Smonou L. Synthesis 2022; 54: 2457

Our synthetic reactions using NaOCl·5H₂O, see:
• 4a Kirihara M, Okada T, Asawa T, Sugiyama Y, Kimura Y. J. Synth. Org. Chem. Jpn. 2020; 78: 11
• 4b Kirihara M, Okada T, Sugiyama Y, Akiyoshi M, Matsunaga T, Kimura Y. Org. Process Res. Dev. 2017; 21: 1925
• 4c Kirihara M, Osugi R, Saito K, Adachi K, Yamazaki K, Matsushima R, Kimura Y. J. Org. Chem. 2019; 84: 8330
• 4d Hakuto N, Saito K, Kirihara M, Kotsuchibashi Y. Polym. Chem. 2020; 11: 2469
• 4e Kirihara M, Suzuki K, Nakakura K, Saito K, Nakamura R, Tujimoto K, Sakamoto Y, Kikkawa Y, Shimazu H, Kimura Y. J. Fluorine Chem. 2021; 243: 109719
• 4f Kirihara M, Adachi K, Sakamoto Y, Tujimoto K, Yamahara S, Matsushima R, Namba Y, Sato K, Kamada T, Kimura Y, Takizawa S. Heterocycles 2021; 103: 699
• 4g Kirihara M, Yamahara S, Okada T, Matsumuro H, Kinoshit Y, Kitajima A, Takamura Y, Odagiri T, Asawa T, Sugiyama Y, Kimura Y. Synthesis 2022; 54: 4120

Selected recent synthetic reactions using NaOCl·5H₂O, see:
• 5a Miller SA, Bisset KA, Leadbeater NE, Eddya NA. Eur. J. Org. Chem. 2019; 1413
• 5b Porcheddu A, Delogu F, De Luca LD, Fattuoni C, Colacino E. Beilstein J. Org. Chem. 2019; 15: 1786
• 5c Uyanik M, Nishioka K, Kondo R, Ishihara K. Nat. Chem. 2020; 12: 353
• 5d Zhu Y, Wang J, Wu D, Yu W. Asian J. Org. Chem. 2020; 9: 1650
• 5e Matsuki S, Kayano H, Takada J, Kono H, Fujisawa S, Saito T, Isogai A. ACS Sustainable Chem. Eng. 2020; 8: 17800
• 5f Umeda T, Minakata S. RSC Adv. 2021; 11: 22120
• 5g Miyamoto K, Okada T, Toyama T, Imamura S, Uchiyama M. Heterocycles 2021; 103: 694
• 5h Miyamoto K, Watanabe Y, Takagi T, Okada T, Toyama T, Imamura S, Uchiyama M. ARKIVOC 2021; (vii): 1
• 5i Kõllo M, Kasari M, Kasari V, Pehk T, Järving I, Lopp M, Jõers A, Kanger T. Beilstein J. Org. Chem. 2021; 17: 581
• 6 The cleavage reaction proceeded even with conventional 13% NaOCl (5.0 eq.) aqueous solution (pH 14), but it took a longer time to complete the reaction (2a, 90% yield). In contrast, the reaction with NaOCl·5H₂O (3.5 eq.) and H₂SO₄ (6.5 eq.) aqueous solution (pH 3) gave the monochlorinated product, 2-chloro-1,3-diphenylpropane-1,3-dione (60% yield), together with 2a (5% yield) and 3a (32% yield), respectively. Under acidic conditions (<pH 3, NaOCl exists as HOCl + Cl₂), the oxidizing ability of NaOCl decreases due to the generation of chlorine gas, resulting in lower yields of target molecules 2a and 3a.
• 7 Commercially available NaOCl·5H₂O crystals are 44% NaOCl and contain minimal amounts of NaOH and NaCl, and the aqueous solution, which is prepared from NaOCl·5H₂O and water, has a pH of 11–12, also see ref 4b.
• 8 Santilli C, Makarov IS, Fristrup P, Madsen R. J. Org. Chem. 2016; 81: 9931
• 9 Salem MS. H, Dubois C, Takamura Y, Kitajima A, Kawai T, Takizawa S, Kirihara M. Green. Chem. 2024; 26: 375
• 10 Das S, Rani ER, Mahanti MK. Kinet. Catal. 2007; 48: 381
• 11 Pícha J, Vanĕk V, Budĕšínský M, Mládková J, Garrow TA, Jiráček J. Eur. J. Med. Chem. 2013; 65: 256
• 12 Yu H, Ru S, Zhai Y, Dai G, Han S, Wei Y. ChemCatChem 2018; 10: 1253
• 13 Lv S.-S, Yan X.-P, Li C.-K, Zhou S.-F, Shoberu A, Zou J.-P. ChemistrySelect 2020; 5: 5670
• 14 Giannopoulos V, Katsoulakis N, Smonou I. Synthesis 2022; 54: 2457
• 15 Xi Z, Liu Y, Wang H, Guan D, Liu Y, Sun B, Tian H, Liang S. ChemistrySelect 2021; 6: 10883