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. 2021 May 28;6(22):14518–14524. doi: 10.1021/acsomega.1c01466

Trifluoroacetic Acid-Mediated Oxidative Self-Condensation of Acetophenones in the Presence of SeO2: A Serendipitous Approach for the Synthesis of Fused [1,3]Dioxolo[4,5-d][1,3]dioxoles

Ibakyntiew D Marpna 1, O Risuklang Shangpliang 1, Kmendashisha Wanniang 1, Baskhemlang Kshiar 1, Tyrchain Mitre Lipon 1, Badaker M Laloo 1, Bekington Myrboh 1,*
PMCID: PMC8190894  PMID: 34124474

Abstract

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A method for the synthesis of fused 1,3-dioxolanes was developed by self-condensation of glyoxal generated in situ by oxidation of acetophenones with SeO2 in the presence of trifluoroacetic acid. Three molecules of the glyoxal generated by oxidation of ketone with SeO2 condensed to form architecturally novel oxygen-containing heterocycles (3a-aryldihydro-[1,3]dioxolo[4,5-d][1,3] dioxole-2,5-diyl)bis(phenylmethanones). This reaction provides a unique methodology for the construction of four C–O bonds in a concerted fashion, generating highly embedded oxygen heterocycles from readily available ketones using affordable shelf reagents and simple reaction conditions.

Introduction

Oxygen-containing heterocyclic molecules occur widely in nature and constitute an important class of compounds because of their diverse biological applications and utility as versatile intermediates in organic synthesis.1 A recent report revealed that oxygen heterocycles are considered as the second most common type of heterocycle that form part of the structural components in many drugs.2 Among them, 1,3-dioxolane is an important moiety frequently encountered as structural motifs in many oxygen-based drugs. Many such compounds have proven to be an effective 5-lipoxygenase inhibitor,3 anti-obesity,4 anti-HIV, anti-cancer,5 and anti-Alzheimer’s.6 Over the past years, various synthetic protocols have been successfully developed for the synthesis of 1,3-dioxolane-based compounds.7 The literature review revealed a wide range of heterocyclic compounds containing one or more 1,3-dioxolane moieties in their molecular framework.8 To the best of our knowledge however, the only available method for the synthesis of fused 1,3-dioxalane was reported by Diels and Jost9 in 1902 by the reaction of biacetyl with HCl to give a product, which was later deduced by Hudec and Turner10 to be a fused dioxole biacetyl trimer (Scheme 1a). Therefore, development of a first method for the synthesis of such compounds having novel structural features will undoubtedly be of interest to synthetic organic chemists, particularly those working in the field of drug development and pharmaceuticals.

Scheme 1. (a, b) Synthesis of Compounds Containing a Fused 1,3-Dioxolane Moiety.

Scheme 1

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Earlier, we have successfully demonstrated that aryl/alkyl ketones react with arenes in the presence of SeO2 and a Lewis acid (BF3·Et2O) to give triaryl ethanones11 via an Umpolung type of electrophilic addition at the α-carbon of the ketones. In the presence of an organic acid (PTSA) however, the aromatic ketones were converted to benzils12 through the Riley oxidation pathway.13 It was observed that the course of the SeO2-mediated reaction is dictated by the nature of the acid as well as the solvent used in a particular set of reactions. Thus, as part of our ongoing research on the synthetic utility of selenium dioxide in organic synthesis,11,12,14 we wish to report here a direct and efficient one-step protocol for the synthesis of oxygen-based fused heterocyclic compounds (3a-aryldihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(phenylmethanones) by self-condensation of arylglyoxals derived from arylketones in the presence of SeO2 and trifluoroacetic acid (TFA) (Scheme 1b).

Results and Discussion

For optimization of the reaction conditions, acetophenone was chosen as the model substrate. Initially, when 1 equiv of acetophenone 1a was treated with 0.5 equiv of SeO2 and 2 equiv of TFA in the presence of nitrobenzene at 40 °C, the condensed product 2a was obtained at only 30% yield (Table 1, entry 1). When the amounts of SeO2 and TFA were simultaneously increased to 1 and 4 equiv, respectively, the yield of product 2a increased to 65% (Table 1, entry 3). An attempt to further increase the amount of either SeO2 or the acid resulted in the formation of multiple spots while lowering the yield of the desired product (Table 1, entries 4 and 5). To further investigate the efficacy of the reaction, different solvents were screened and it was found that the reaction proceeded well with aromatic solvents like nitrobenzene, benzene, chlorobenzene, and toluene (Table 1, entries 3 and 6–8) but showed negative results with non-aromatic solvents like DMSO, acetonitrile, and DMF (Table 1, entries 9–11). Of all the aromatic solvents employed, it was found that the optimum yields were obtained when the reactions were carried out with nitrobenzene as the solvent (Table 1, entry 3). Next, the reactions were performed under the standard condition using the Lewis acid BF3·Et2O and protonic acids such as acetic acid and sulfuric acid to see if there was any improvement in the yields. The use of BF3·Et2O resulted in an intractable mass, while the two protonic acids did not give any product at all (Table 1, entries 12–14). It may be noted that product 2a was not obtained in the absence of either TFA or SeO2 even when the reaction temperature was increased up to 60 °C (Table 1, entries 15 and 16). Thus, the optimum condition for the reaction to give a satisfactory yield of 65% for compound 2a requires 1 equiv of SeO2, 4 equiv of TFA, employing nitrobenzene as the solvent at 40 °C, and a maximum reaction time of 2 h (Table 1, entry 3).

Table 1. Optimization of Reaction Conditionsa.

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Sl no. SeO2 (equiv) acid (equiv) solvent temperature (°C) yield (%)b
1 0.5 TFA (2) nitrobenzene 40 30
2 0.5 TFA (4) nitrobenzene 40 45
3 1 TFA (4) nitrobenzene 40 65
4 1.5 TFA (4) nitrobenzene 40 40
5 1 TFA (5) nitrobenzene 40 55
6 1 TFA (4) benzene 40 50
7 1 TFA (4) chlorobenzene 40 60
8 1 TFA (4) toluene 40 50
9 1 TFA (4) DMSO 60  
10 1 TFA (4) acetonitrile 60  
11 1 TFA (4) DMF 60  
12 1 BF3·EtOH nitrobenzene 60  
13 1 acetic acid nitrobenzene 60  
14 1 sulfuric acid nitrobenzene 60  
15   TFA (4) nitrobenzene RT-60c  
16 1   nitrobenzene RT-60c  
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a

Reaction was carried out with 1 equiv of 1a.

b

Isolated yield.

c

Initially, the reaction was carried out at room temperature and then heated to 60 °C.

Equipped with the optimized reaction conditions, we proceeded to investigate the generality of the method by carrying out reactions with differently substituted aryl methyl ketones. It was observed that both electron-donating and electron-withdrawing substituents are equally compatible for the reaction to give products in moderate to good yields. Thus, irrespective of the nature of substitution on the benzene ring of the ketones, the p-substituted aryl methyl ketones (p-CH3, p-OCH3, p-Br, p-Cl, and p-F) reacted easily to give the corresponding products in satisfactory yields (2b, 70%; 2c, 68%; 2d, 70%; 2e, 72%; 2f, 75%) (Scheme 2). Similarly, m-substituted ketones (m-Cl, m-Br, and m-CH3) displayed comparable reactivity, generating the desired products (2g, 60%; 2h, 52%; 2i, 62%) in moderate yields. It may be noted that o-substituted ketones (o-CH3 and o-OCH3) also reacted albeit with lesser product yields (2j, 50% and 2k, 52%), presumably due to steric hindrance. The effect is more pronounced with trisubstituted ketone (1n) when the reaction failed to react altogether. Disubstituted ketone (1l) also reacted to give the product 2l in 55% yield. The scope of the reaction was further extended to 2-acetylnaphthalene (1m), which successfully underwent self-condensation to give the product 2m in reasonable yield. With heteroaryl methyl ketones (1o and 1p) however, the reactions gave only trace amounts of the products (2o and 2p). The structures of some of these new compounds (2a, 2b, 2e, 2j, 2k, and 2l) were confirmed by X-ray diffraction analysis (included in the Supporting Information). The Oak Ridge Thermal-Ellipsoid Plot (ORTEP) diagram representation of compounds 2a and 2e is shown in Figure 1. From the above results, it is evident that the formation of the product is not defined by the nature of the substituents on the benzene ring of the ketones but rather depends on the position of the substituents where unsubstituted and p-substituted aryl methyl ketones (1a–f) gave the maximum yield of the condensed product, whereas substitution at the o-position (1j–l) resulted in lesser product yields. 1H NMR and ORTEP diagrams of few products (2b, 2f, 2h, 2k, and 2m) indicated the presence of a mixture of symmetrical and unsymmetrical isomers. Heteronuclear Multiple Bond Coherence (HMBC) analysis of compound 2f confirmed the presence of both the isomers. It was further observed from 1H NMR that o-substituted ketones (1j, 1k, and 1l) afforded the symmetric products 2j, 2k, and 2l, although 2k gave a mixture of symmetrical and unsymmetrical forms. The p- and m-substituted ketones however yielded unsymmetrical isomers as the major product. Thus, it appears that o-substituents effect the formation of symmetric products may be due to the steric repulsion.

Scheme 2. Scope of Self-Condensation of Aryl Methyl Ketonesa in the Presence of SeO2 and TFA.

Scheme 2

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The reaction was carried out with 1a (2.0 mmol, 1 equiv), SeO2 (0.222 g, 2.0 mmol, 1 equiv), and TFA (0.6 mL, 4 equiv) in nitrobenzene at 40 °C.

Isolated yield.

Figure 1.

Figure 1

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ORTEP of 2a (CCDC 1991160) and 2e (CCDC 1991162), with thermal ellipsoids at the 50% probability level.

The plausible mechanistic pathway is depicted in Scheme 3. Evidently, the initial step of the reaction involves the well-established Riley oxidation of the acetophenone 1a by SeO2 to gyloxal 3, which, in the presence of TFA, existed in equilibrium with its monohydrated substrate 4.15 A concerted acid-catalyzed double acetalization of the glyoxal with two molecules of its monohydrate resulted in the formation of the condensed product 2a with elimination of water. The above proposed mechanism was further strengthened by the condensation of 2,2-dihydroxy-1-(p-tolyl)ethan-1-one 4b in the presence of acid TFA under the standard reaction condition to give the expected product 2b in 76% yield (Scheme 4).

Scheme 3. Plausible Mechanism.

Scheme 3

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Scheme 4. Condensation of 2,2-Dihydroxy-1-(p-tolyl)ethan-1-one to 2b.

Scheme 4

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Conclusions

In summary, this work highlights a new TFA-mediated intermolecular oxidative self-condensation reaction of three molecules of aromatic ketone via multiple C–O bond formations using a common shelf reagent, SeO2, as the oxidant under mild reaction conditions to afford (3a-phenyldihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(phenylmethanones), a structurally unique class of oxygen heterocycles.

Experimental Section

All chemicals and reagents were purchased from available commercial companies and were used without further purification. Reactions were monitored by thin-layer chromatography using pre-coated aluminum sheets (silica gel 60 F254, 0.2 mm thickness). Formation of the desired product was confirmed by infrared (IR), 1H NMR, 13C NMR, and mass spectra (LC–MS/HRMS). IR spectra were recorded on a Perkin Elmer Spectrum 400 FTIR instrument, and the frequencies are expressed in cm–1. 1H NMR and 13C NMR spectra were recorded on a Bruker Avance II-400 spectrometer in CDCl3, and chemical shifts were recorded in ppm with TMS as the internal standard. The HMBC spectrum was recorded on an ECZR series 600 MHz NMR spectrometer (Jeol, Japan). Melting points were recorded by an open capillary tube method. Mass spectral data were obtained with a Waters UPLC-TQD mass spectrometer (ESI-MS). High-resolution mass spectra (ESI-HRMS) were recorded on an Agilent 6545 Quadrupole Time-of-Flight. All reactions were purified by column chromatography over silica gel (100–200 mesh) using ethyl acetate and hexane as the eluent.

General Procedure for the Preparation of (3a-Aryldihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(phenylmethanone)

To a solution of nitrobenzene (5 mL) and aryl methyl ketone (1a–p) (2.0 mmol, 1 equiv) in a 25 mL dry round-bottom flask, SeO2 (0.222 g, 2.0 mmol, 1 equiv) was added and the mixture was allowed to stir in an ice bath where TFA (0.6 mL) was added dropwise. The reaction was then allowed to stir at 40 °C for 2 h using a temperature-controlled magnetic stirrer in an oil bath. After the reaction is completed, ethyl acetate (20 mL) was added to dilute the reaction mixture, which was then washed with a saturated solution of sodium bicarbonate and thereafter with brine solution. The organic layer was then collected separately and dried over anhydrous sodium sulfate and reduced in a rotatory evaporator to a minimum amount. The compound was then purified by column chromatography over a silica gel 100–200 mesh using ethyl acetate:hexane as the eluent.

(3a-Phenyldihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(phenylmethanone) (2a)

The product was prepared via the general procedure from acetophenone 1a (0.240 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (9:1) as the eluent; white solid (0.174 g, 65%); mp 120–122 °C; IR (KBr): 3065, 3032, 2923, 1701, 1596, 1451, 1113, 1071, 857, 689 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 7.2 Hz, 4H), 7.59 (t, J = 7.2 Hz, J = 7.6 Hz, 2H), 7.51–7.45 (m, 6H), 7.29–7.27 (m, 3H), 6.53 (s, 2H), 5.95 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 188.50, 133.45, 133.09, 132.35, 128.68, 128.43, 127.87, 127.48, 125.47, 111.74, 105.89, 101.23 ppm. MS (ES+) calcd for C24H18O6, 402.1; found m/z, 425.1 [M + Na]+.

(3a-(p-Tolyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(p-tolylmethanone) (2b)

The product was prepared via the general procedure from 4-methylacetophenone 1b (0.268 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (9:1) as the eluent. The product was collected as a mixture of isomers; white solid (0.201 g, 70%); mp 130–131 °C; IR (KBr): 3076, 3010, 2947, 1689, 1596, 1289, 1163, 1104, 1045, 759 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.26–7.20 (m, 4H), 7.13 (d, J = 8 Hz, 2H), 6.47 (s, 1H), 6.30 (s, 1H), 5.84 (s, 1H), 2.37 (s, 3H), 2.34 (s, 3H), 2.28 (s, 3H), 6.49 (s, 2H), 5.91 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.83, 189.67, 145.43, 145.37, 139.65, 131.93, 131.08, 131.03, 129.58, 129.56, 129.50, 129.23, 126.20, 113.18, 107.04, 103.58, 101.39, 21.86, 21.24 ppm. MS (ES+) calcd for C27H24O6, 444.1; found m/z, 467.1 [M + Na]+.

(3a-(4-Methoxyphenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((4-methoxyphenyl)methanone) (2c)

The product was prepared via the general procedure from 4-methoxyacetophenone 1c (0.300 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (6:4) as the eluent; white solid (0.222 g, 68%); mp 120–122 °C; IR (KBr): 3071, 3005, 2961, 2840, 1689, 1598, 1250, 1114, 1027, 827, 601 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.8 Hz, 2H), 8.00 (d, J = 9.2 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 6.93–6.83 (m, 6H), 6.45 (s, 1H), 6.29 (s, 1H), 5.82 (s, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 3.74 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 190.65, 188.50, 164.36, 160.54, 131.92, 131.88, 127.72, 126.94, 126.59, 126.47, 114.09, 114.04, 113.83, 113.06, 106.91, 103.48, 101.18, 55.59, 55.55, 55.33 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C27H25O9, 493.1499; found, 493.1491.

(3a-(4-Bromophenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((4-bromophenyl)methanone) (2d)

The product was prepared via the general procedure from 4-bromoacetophenone 1d (0.398 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent; white solid (0.298 g, 70%); mp 132–134 °C; IR (KBr): 3090, 2912, 2576, 1707, 1584, 1127, 1071, 869, 814 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.63–7.58 (m, 4H), 7.47 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 6.46 (s, 1H), 6.21 (s, 1H), 5.83 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.25, 188.99, 133.48, 132.32, 132.28, 131.94, 131.86, 131.84, 130.86, 130.78, 130.03, 130.00, 128.03, 124.33, 112.76, 106.90, 103.65, 101.47 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C24H16Br3O6, 638.8477; found, 638.8469.

(3a-(4-Chlorophenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((4-chlorophenyl)methanone) (2e)

The product was prepared via the general procedure from 4-chloroacetophenone 1e (0.309 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent; white solid (0.245 g, 72%); mp 132–136 °C; IR (KBr): 3021, 2927, 2929, 1714, 1702, 1589, 1172, 1094, 830, 759 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.8 Hz, 2H), 8.01 (d, J = 9.2 Hz, 2H), 7.56–7.48 (m, 6H), 7.39 (d, J = 8.8 Hz, 2H), 6.53 (s, 1H), 6.30 (s, 1H), 5.91 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.04, 188.79, 141.17, 141.12, 136.07, 133.02, 131.61, 131.54, 130.84, 130.76, 129.34, 129.29, 128.88, 127.78, 112.75, 106.98, 103.67, 101.49 ppm. MS (ES+) calcd for C24H15Cl3O6, 503.9; found m/z, 526.9 [M + Na]+.

(3a-(4-Fluorophenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((4-fluorophenyl)methanone) (2f)

The product was prepared via the general procedure from 4-fluoroacetophenone 1f (0.276 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent. The product was collected as a mixture of isomers; white solid (0.228 g, 75%); mp 109–111 °C; IR (KBr): 3079, 2934, 1705, 1601, 1512, 1243, 1127, 836 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.14–8.10 (m, 4H), 7.56–7.53 (m, 2H), 7.17–7.10 (m, 6H), 6.48 (s, 2H), 5.84 (s, 1H), 8.07–8.04 (m, 4H), 7.51–7.48 (m, 2H), 7.05–6.97 (m, 6H), 6.48 (s, 1H), 6.26 (s,1H), 5.90 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 190.63, 188.38, 187.85, 166.53 (d, JC–F = 257 Hz), 166.44 (d, JC–F = 255 Hz), 163.60 (JC–F = 248 Hz), 132.39–132.27 (m), 128.62 (d, JC–F = 8.7 Hz), 128.40 (d, JC–F = 8.6 Hz), 116.41–116.10 (m), 115.66 (d, JC–F = 21 Hz), 115.60 (d, JC–F = 22 Hz), 112.78, 112.48, 106.97, 106.74, 103.62, 102.07, 101.43 ppm. HMBC cross peak: δ 5.86/101.43, 5.86/103.62, 5.86/112.78, 6.55/188.38, 7.12–7.17/132.26, 7.12–7.17/115.77, 7.12–7.17/167.82, 7.53–7.56/112.78, 7.53–7.56/128.66, 7.53–7.56/112.78, 8.11–8.14/132.39, 8.11–8.14/167.82; δ 5.96/102.07, 5.96/112.48, 6.32/187.85, 6.50/190.63, 6.50/112.48, 6.50/106.74, 6.96–7.05/115.56, 6.96–7.05/132.26, 6.95–7.05/164.84, 7.48–7.51/112.48, 7.48–7.51/128.44, 7.48–7.51/164.84, 8.04–8.07/132.26, 8.04–8.07/167.72, 8.04–8.07/187.85. HRMS (ESI) m/z: [M + H]+ calcd for C24H16F3O6, 457.0899; found, 457.0891.

(3a-(3-Chlorophenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((3-chlorophenyl)methanone) (2g)

The product was prepared via the general procedure from 3-chloroacetophenone 1g (0.309 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent; yellow thick liquid (0.202 g, 60%); IR (KBr): 3069, 2923, 1708, 1571, 1427, 1235, 1171, 1032, 791 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.98–7.88 (m, 3H), 7.58–7.54 (m, 3H), 7.45–7.41 (m, 3H), 7.35–7.29 (m, 2H), 6.49 (s, 1H), 6.23 (s, 1H), 5.87 (1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.31, 189.04, 136.60, 135.63, 135.58, 135.02, 134.99, 134.95, 134.72, 133.34, 130.59, 130.55, 130.41, 130.33, 129.65, 129.44, 127.89, 127.87, 126.89, 124.87, 112.78, 107.20, 103.97, 101.86 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C24H16Cl3O6, 505.0012; found, 505.0013.

(3a-(3-Bromophenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((3-bromophenyl)methanone) (2h)

The product was prepared via the general procedure from 3-bromoacetophenone 1h (0.398 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent. The product was collected as a mixture of isomers; yellow thick liquid (0.221 g, 52%); IR (KBr): 3067, 2922, 2852, 1707, 1566, 1120, 1032, 788 cm–1; 1H NMR (400 MHz, CDCl3): δ 8.20 (s, 1H), 8.11 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.73–7.69 (m, 3H), 7.48 (t, J = 8.8 Hz, J = 8.4 Hz, 2H), 7.39–7.32 (m, 2H), 7.24 (d, J = 8 Hz, 1H), 6.48 (s, 1H), 6.22 (s, 1H), 5.86 (s, 1H), 6.46 (s, 2H), 5.93 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 190.95, 188.69, 137.36, 136.51, 135.98, 134.88, 133.07, 132.29, 132.08, 130.54, 130.49, 130.30, 129.48, 128.06, 126.86, 125.08, 123.31, 123.31, 122.74, 112.40, 106.98, 103.66, 102.15, 101.54 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C24H16Br3O6, 638.8477; found, 638.8471.

(3a-(m-Tolyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(m-tolylmethanone) (2i)

The product was prepared via the general procedure from 3-methylacetophenone 1i (0.268 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (9:1) as the eluent; yellow thick liquid (0.183 g, 62%); IR (KBr): 2922, 1702, 1605, 1262, 1115, 1035, 788 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.90–7.81 (m, 4H), 7.39–7.32 (m, 6H), 7.22 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 7.2 Hz, 1H), 6.50 (s, 1H), 6.32 (s, 1H), 5.87 (s, 1H), 2.37 (s, 3H), 2.35 (s, 3H), 2.30 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 190.20, 189.76, 138.81, 138.78, 138.67, 138.39, 138.27, 135.31, 135.16, 134.63, 134.04, 130.47, 129.82, 129.72, 129.32, 128.75, 128.70, 128.50, 128.42, 128.07, 126.86, 126.81, 126.77, 107.06, 106.93, 103.64, 102.32, 101.46, 21.49, 21.42, 21.40 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C27H25O6, 445.1651; found, 445.1646.

(3a-(o-Tolyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(o-tolylmethanone) (2j)

The product was prepared via the general procedure from 2-methylacetophenone 1j (0.268 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (9:1) as the eluent; white solid (0.147 g, 50%); mp 128–130 °C ; IR (KBr): 3065, 2972, 2928, 2873, 1702, 1599, 1111, 864, 741 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.2 Hz, 2H), 7.60 (d, J = 8 Hz, 1H), 7.39 (t, J = 6.4 Hz, J = 7.6 Hz, 2H), 7.26–7.23 (m, 4H), 7.16 (d, J = 6.4 Hz, 1H), 7.07–7.05 (m, 2H), 6.39 (s, 2H), 6.17 (s, 1H), 2.47 (s, 6H), 2.23 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.87, 191.67, 139.96, 139.83, 136.17, 132.80, 132.72, 132.30, 132.17, 131.80, 131.78, 131.66, 131.60, 131.39, 131.34, 129.95, 129.55, 129.42, 129.40, 129.26, 127.06, 126.63, 125.48, 125.35, 125.31, 125.29, 113.10, 112.67, 105.13, 104.80, 102.42, 102.06 ppm. MS (ES+): calcd for C27H24O6, 444.1; found m/z, 467.2 [M + Na]+.

(3a-(2-Methoxyphenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((2-methoxyphenyl)methanone) (2k)

The product was prepared via the general procedure from 2-methoxyacetophenone 1k (0.300 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (6:4) as the eluent. The product was collected as mixture of isomers; white solid (0.170 g, 52%); mp 128–130 °C; IR (KBr): 3076, 3010, 2843, 1689, 1596, 1487, 1289, 1247, 1104, 1045, 870, 759 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.72–7.69 (m, 3H), 7.55–7.49 (m, 3H), 7.07–6.98 (m, 6H), 6.47 (s, 1H), 6.41 (s, 1H), 6.12 (s, 1H), 3.98 (s, 3H), 3.93 (s, 3H), 3.82 (s, 3H), 7.81–7.73 (m, 3H), 7.36–7.31 (m, 3H) ppm; 6.95–6.87 (m, 6H), 6.58 (s, 2H), 6.19 (s, 1H), 3.96 (s, 6H), 3.70 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 195.66, 193.26, 193.21, 159.43, 159.13, 158.95, 156.87, 156.79, 134.55, 134.47, 130.82, 130.80, 128.44, 128.37, 125.66, 125.38, 125.30, 123.48, 121.04, 120.94, 120.68, 120.28, 120.05, 112.17, 112.09, 111.95, 111.023, 110.89, 105.60, 105.53, 104.67, 103.83, 103.23, 56.12, 55.98, 55.90, 55.37, 55.10 ppm. MS (ES+) calcd for C27H24O9, 492.1; found m/z, 493.2 [M + H]+.

(3a-(2,4-Dimethylphenyl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis((2,4-dimethylphenyl)methanone) (2l)

The product was prepared via the general procedure from 2,4-Dimethylacetophenone 1l (0.296 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (8:2) as the eluent; white solid (0.178 g, 55%); mp 134–135 °C; IR (KBr): 3032, 2967, 2922, 1712, 1614, 1107,845, 656 cm–1; 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8 Hz, 1H), 7.04 (d, J = 6.4 Hz, 4H), 6.88–6.85 (m, 2H), 6.39 (s, 2H), 6.13 (s, 1H), 2.46 (s, 6H), 2.30 (s, 6H), 2.19 (s, 6H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ 191.40, 143.76, 140.96, 139.57, 136.44, 133.20, 132.67, 130.56, 130.39, 128.79, 127.64, 126.45, 126.37, 113.17, 105.30, 102.41, 21.69, 21.59, 20.93, 20.31 ppm. MS (ES+) calcd for C30H30O6, 486.2; found m/z, 509.1 [M + Na].

(3a-(Naphthalen-2-yl)dihydro-[1,3]dioxolo[4,5-d][1,3]dioxole-2,5-diyl)bis(naphthalen-2-ylmethanone) (2m)

The product was prepared via the general procedure from 1-(naphthalen-2-yl)ethan-1-one 1m (0.340 g, 2.0 mmol, 1 equiv) in the presence of SeO2 (0.222 g, 2.0 mmol, 1 equiv) and TFA (0.6 mL). The crude was purified by column chromatography using hexane:ethyl acetate (5:5) as the eluent. The product was collected as a mixture of isomers; white solid (0.169 g, 46%); mp 179–180 °C; IR (KBr): 3056, 2929, 2854, 1706, 1625, 1271, 1191, 1108, 821, 752 cm–1; 1H NMR (400 MHz, CDCl3: DMSO-d6): δ 8.75 (s, 1H), 8.55 (s, 1H), 8.15–8.14 (m, 2H), 8.02–7.94 (m, 3H), 7.89–7.80 (m, 7H), 7.63–7.50 (m, 5H), 7.48–7.45 (m, 2H), 6.93 (s, 1H), 6.55 (s, 1H), 6.05 (s, 1H); 7.02 (s, 2H), 6.08 (s, 1H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6: acetone-d6): δ 193.03, 190,37, 135.93, 133.74, 132.88, 132.72, 132.47, 132.30, 132.13, 131.60, 131.57, 131.27, 130.20, 130.10, 129.72, 129.64, 129.11, 128.98, 128.81, 128.70, 128.21, 128.01, 127.67, 127.61, 127.48, 127.133, 126.13, 124.55, 124.19, 123.94, 113.08, 106.65, 103.99, 101.63 ppm. HRMS (ESI) m/z: [M + H]+ calcd for C36H25O6, 553.1651; found, 553.1648.

Acknowledgments

The authors thank the financial support of University Grants Commission (UGC), India, under the Maulana Azad National Fellowship for Minority (MANF) Scheme. The authors acknowledge SAIF-NEHU, SAIF-CDRI Lucknow for spectral analysis. The authors gratefully acknowledge DST-PURSE for crystallographic analysis. B.M. acknowledges financial assistance from SERB, DST (SB/EMEQ-006/3013).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c01466.

  • Crystallographic data of compounds 2a, 2b, 2e, 2j, 2k, and 2l (CIF)

    Single-crystal XRD data of 2a, 2b, 2e, 2j, 2k, and 2l; 1H and 13C NMR spectra of synthesized compounds; and HMBC spectrum of 2f (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao1c01466_si_001.cif (2MB, cif)
ao1c01466_si_002.pdf (1.3MB, pdf)

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Associated Data

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Supplementary Materials

ao1c01466_si_001.cif (2MB, cif)
ao1c01466_si_002.pdf (1.3MB, pdf)

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