Synthesis of 1-Thiaphenalene Derivatives via Radical Cyclization of 1-Naphthalenesulfonyl Chlorides with Alkynes

Dedicated to Professor Shigeru Yamago on the occasion of his 60^th birthday

Abstract

Functionalized thiaphenalene derivatives are of high synthetic value, yet their preparation remains underexplored. Herein, we report an efficient approach for the synthesis of 1-thiaphenalene derivatives through radical cyclization of 1-naphthalenesulfonyl chlorides with alkynes. A variety of 1-thiaphenalene derivatives are readily furnished that are otherwise difficult to prepare by present methods. The protocol features mild photocatalytic conditions, broad functional-group compatibility, and high product diversity.

The thiaphenalene structural motif plays an important role in organic electroluminescent devices, in which the placement of the thiaphenalene may improve the luminous efficiency and prolong the service life (Scheme [1a]).[1] Establishing concise approaches for access to thiaphenalene derivatives is a long-term interest for synthetic chemists, yet remains underexplored.[2] Radical reactions supply a robust toolbox to produce multitudinous valuable cyclic compounds by adding free radicals to unsaturated chemical bonds.[3] As disclosed by Nakamura, Nevado, and their respective co-workers,[4] [5] the sulfonyl radical can be delivered from 1-naphthalenesulfonyl chloride under transition-metal (Fe or Ni) catalysis and then added to alkynes to generate the sulfonylvinyl radical. The ensuing transformation of this radical intermediate proceeds via either atom transfer radical addition (ATRA) to give the chlorosulfonylation product or cross-coupling with arylboronic acids (Scheme [1b]). Notably, in these reactions thiaphenalenes were obtained as byproducts, but the yields were far from useful.

Herein, we report an efficient approach for the synthesis of 1-thiaphenalene derivatives through radical cyclization of 1-naphthalenesulfonyl chlorides with alkynes. Under photoredox catalytic conditions, the cyclization occurs prior to the common ATRA process.[6] The reaction demonstrates broad functional-group compatibility and high product diversity (Scheme [1c]).

Table 1 Reaction Parameters Survey^a

Entry	Photocatalyst	hv (W)	1a (equiv)	Solvent	Yield (%)b
1	fac-Ir(ppy)3	30	1.5	MeCN	70
2	Ir[dF(CF3)ppy]2(dtbbpy) (PF6)	30	1.5	MeCN	46
3	Ir(ppy)2(dtbbpy)(PF6)	30	1.5	MeCN	57
4	Ru(bpy)3Cl2	30	1.5	MeCN	9
5	fac-Ir(ppy)3	30	1.5	THF	67
6	fac-Ir(ppy)3	30	1.5	EtOH	52
7	fac-Ir(ppy)3	30	1.5	EtOAc	66
8c	fac-Ir(ppy)3	30	1.5	MeCN	68
9d	fac-Ir(ppy)3	30	1.5	MeCN	49
10	fac-Ir(ppy)3	18	1.5	MeCN	66
11	fac-Ir(ppy)3	50	1.5	MeCN	72
12	fac-Ir(ppy)3	50	1.0	MeCN	45
13	fac-Ir(ppy)3	50	2.0	MeCN	75
14e	fac-Ir(ppy)3	–	2.0	MeCN	trace
15f	–	50	2.0	MeCN	trace
16g	fac-Ir(ppy)3	50	2.0	MeCN	55
17h	fac-Ir(ppy)3	50	2.0	MeCN	26

^a Reaction conditions: 1a (as shown in table), 2a (0.2 mmol, 1.0 equiv), photocatalyst (3 mol%), Na₂HPO₄ (0.2 mmol, 1.0 equiv), solvent/H₂O (1 mL/0.1 mL), blue LED irradiation, N₂, RT.

^b Yields after isolation.

^c MeCN (1.5 mL).

^d MeCN (2.0 mL).

^e In the dark.

^f Without photocatalyst.

^g Without H₂O as cosolvent.

^h Under air.

At the outset, the optimization of reaction conditions was implemented with the use of 1-naphthalenesulfonyl chloride (1a) and propargylic alcohol 2a as model substrates. An initial attempt was performed with fac-Ir(ppy)₃ as the photosensitizer and Na₂HPO₄ as the base in a MeCN/H₂O cosolvent mixture under 30 W blue LED irradiation. To our delight, desired product 3a was obtained in 70% yield (Table [1], entry 1), and its structure was verified by single-crystal diffraction.[7] A brief screening of photocatalysts indicated that fac-Ir(ppy)₃ was more suitable than others (entries 2–4). The influence of solvent was considered, but no positive results were afforded by changing the solvent or the volume of solvent (entries 5–9). An examination of the base showed that different bases had little impact on the reaction outcomes (see the Supporting Information, Table S1). Increases in the light intensity or the amount of 1a could both improve the yield of product (entries 10–13). Furthermore, control experiments showed that the light and photocatalyst were crucial to the reaction (entries 14 and 15). Performing the reaction in pure MeCN solution or under air compromised the reaction outcomes (entries 16 and 17).

With the optimized reaction conditions in hand, we began to explore the substrate scope for the reaction (Scheme [2]). Various propargylic alcohols were suitable substrates for the reaction, regardless of steric congestion from the neighboring quaternary carbon center (3a–3d). Scaling up the reaction tenfold under the same conditions delivered a comparable yield of 3a. Aliphatic alkynes with or without substituents were apt to generate the corresponding products (3e–3o). Notably, many susceptible groups, such as iodide (3l) and unprotected alcohol (3m), were tolerated in the reaction. Notwithstanding the moderate yield, the example of 3n was noteworthy, because the alkenyl radical intermediate could also undergo competitive 1,5-hydrogen abstraction from the benzyl C(sp³)–H bonds instead of the desired cyclization. The same phenomenon could also happen with 3o, decreasing the yield of isolated product. Moreover, the presence of an internal alkyne did not interfere with the site selectivity for the terminal alkyne (3o). The reaction with electron-deficient propionate also proceeded, albeit with a lower yield (3p). Remarkably, the reaction readily occurred with internal alkynes (3q and 3r). For the unsymmetrical phenyl propionate, the reaction showed exclusive regioselectivity (3r). However, the conversion of aryl alkynes, regardless of electronic characteristics, consistently resulted in low yields (3s–3u), which might be attributable to sluggish cyclization of the relatively stable benzyl radical with the naphthyl group. The reaction of naphthalenesulfonyl chlorides bearing extra substituents also proceeded readily, leading to multifunctionalized thiaphenalene derivatives in good yields (3v–3x).

Based on the experimental results and previous reports, a plausible reaction mechanism is depicted in Scheme [3]. The overall transformation proceeds via radical pathways. Addition of 3.0 equiv of butylated hydroxytoluene (BHT) to the reaction significantly suppressed the formation of desired product 3a, and the trapping product 4 was detected by HRMS. The reaction is initiated by single-electron transfer (SET) between the excited Ir(III)* species (E _1/2 = –1.73 V vs. SCE in CH₃CN)[8] and sulfonyl chloride 1 (E _1/2 = –0.59 V vs. SCE in CH₃CN). Sulfonyl radical a is delivered, which then adds to alkyne 2 to form vinyl radical b. The ensuing intramolecular cyclization of b takes place over competitive pathways, such as vinyl radical-mediated halogen-atom transfer (XAT) or hydrogen-atom transfer (HAT) to generate d, and radical intermediate c is formed. Single-electron oxidation of c to cation e by Ir(IV) generated in situ, followed by deprotonation, furnishes final product 3. Meanwhile, catalytic species Ir(III) is regenerated and perpetuates the catalytic cycle.

In conclusion, we have disclosed an efficient radical approach for the synthesis of valuable 1-thiaphenalene derivatives, a reaction that is rarely explored by other methods. The intermolecular cyclization of various 1-naphthalenesulfonyl chlorides and alkynes readily proceeds under mild photoredox catalysis. The protocol features broad functional-group tolerance and high product diversity, and it provides a practical method for the preparation of 1-thiaphenalenes, which may find uses in the development of organic light-emitting diodes.

All reactions were maintained under a nitrogen atmosphere unless otherwise stated. Commercially available reagents were used without further purification. Infrared (FT-IR) spectra were recorded on a Bruker Vertex 70 instrument as ν _max in cm^–1. ¹H NMR spectra were recorded on a Bruker Avance III HD (400 MHz) spectrometer. Chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl₃: δ = 7.26; DMSO-d ₆: δ = 2.50). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, br = broad, m = multiplet), coupling constants (Hz), and integration. ¹³C NMR spectra were recorded on a Bruker Avance III HD (100 MHz) spectrometer with complete proton decoupling. Chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl₃: δ = 77.16; DMSO-d ₆: δ = 39.52). Mass spectra were measured with an Agilent Technologies 6120 Quadrupole LC/MS instrument. High-resolution mass spectrometry (HRMS) was performed with GCT Premier^TM and Bruker micrOTF-Q III instruments. Melting points were measured by using an INESA WRR apparatus, and values are uncorrected.

1-Naphthalenesulfonyl chlorides were synthesized according to the reported procedures.[9]

Products 3; General Procedure

1-Naphthalenesulfonyl chloride 1 (0.4 mmol, 2.0 equiv), alkyne 2 (0.2 mmol, 1.0 equiv), fac-Ir(ppy)₃ (3.9 mg, 3 mol%), and Na₂HPO₄ (0.2 mmol, 1.0 equiv) were loaded in a reaction vial. Mixed solvent, CH₃CN/H₂O (1.0 mL/0.1 mL), was added under a nitrogen atmosphere. The reaction mixture was then stirred at room temperature under 50 W blue LED irradiation for 10 h. After reaction completion, the resultant solution was concentrated and purified by flash column chromatography on silica gel to give the corresponding product 3.

3-(1-Hydroxy-1-phenylethyl)benzo[de]thiochromene 1,1-Dioxide (3a)

Yield: 50.7 mg (75%), white solid, mp 117–118 °C, purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3448, 3067, 2979, 2855, 1624, 1492, 1393, 1364, 1268, 1112, 763 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.41 (dd, J = 7.2, 1.6 Hz, 1 H), 8.09 (dd, J = 8.4, 1.2 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 8.0 Hz, 1 H), 7.74–7.70 (m, 1 H), 7.52–7.49 (m, 2 H), 7.45 (s, 1 H), 7.34–7.25 (m, 4 H), 2.95 (br s, 1 H), 1.98 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 149.2, 145.5, 134.5, 133.2, 133.1, 132.6, 131.3, 129.0, 127.9, 126.2, 126.0, 125.6, 124.9, 124.8, 123.3, 121.6, 76.7, 31.3.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₆O₃SNa: 359.0712; found: 359.0702.

3-(2-Hydroxypropan-2-yl)benzo[de]thiochromene 1,1-Dioxide (3b)

Yield: 36.7 mg (71%); yellow solid; mp 173–174 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3395, 3348, 3068, 2953, 2922, 1627, 1460, 1180, 1134, 761 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.41 (dd, J = 7.2, 1.6 Hz, 1 H), 8.40 (dd, J = 7.2, 1.2 Hz, 1 H), 8.17 (dd, J = 8.0, 1.2 Hz, 1 H), 7.99 (d, J = 8.0 Hz, 1 H), 7.78–7.74 (m, 1 H), 7.66–7.62 (m, 1 H), 7.05 (s, 1 H), 2.50 (s, 1 H), 1.76 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 150.5, 134.6. 132.9, 132.3, 131.6, 126.4, 126.0, 125.6, 125.0, 122.2, 121.8, 74.0, 31.1.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₆O₃S: 275.0736; found: 275.0735.

3-(1-Hydroxycyclohexyl)benzo[de]thiochromene 1,1-Dioxide (3c)

Yield: 31.5 mg (50%); white solid; mp 146–147 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3440, 3059, 2924, 1619, 1461, 1361, 1313, 1176 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.04 (d, J = 8.0 Hz, 1 H), 8.40 (d, J = 7.2 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 7.99 (d, J = 8.4 Hz, 1 H), 7.78–7.74 (m, 1 H), 7.67–7.63 (m, 1 H), 6.97 (s, 1 H), 2.17–2.12 (m, 3 H), 1.91–1.68 (m, 7 H).

¹³C NMR (100 MHz, CDCl₃): δ = 150.9, 134.6, 132.9, 132.7, 132.6, 131.5, 126.4, 125.9, 125.4, 125.1, 122.2, 122.1, 75.0, 37.9, 25.5, 21.8.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₁₈O₃SNa: 337.0869; found: 337.0859.

3-(Hydroxy(phenyl)methyl)benzo[de]thiochromene 1,1-Dioxide (3d)

Yield: 46.0 mg (71%); white solid; mp 209–210 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3504, 3041, 3003, 2921, 1625, 1584, 1454, 1274, 1140, 763 cm^–1.

¹H NMR (400 MHz, DMSO-d ₆): δ = 8.45 (d, J = 7.6 Hz, 1 H), 8.39 (d, J = 8.0 Hz, 1 H), 8.19–8.15 (m, 2 H), 7.94–7.90 (m, 1 H), 7.67–7.63 (m, 1 H), 7.50–7.49 (m, 3 H), 7.35–7.32 (m, 2 H), 7.26–7.23 (m, 1 H), 6.52 (br s, 1 H), 6.24 (s, 1 H).

¹³C NMR (100 MHz, DMSO-d ₆): δ = 147.4, 142.7, 135.0, 133.8, 132.6, 132.3, 130.4, 129.0, 128.3, 127.4, 127.3, 127.2, 126.0, 123.8, 123.1, 121.9, 71.9.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₄O₃SNa: 345.0556; found: 345.0559.

3-Propylbenzo[de]thiochromene 1,1-Dioxide (3e)

Yield: 38.2 mg (74%); white solid; mp 117–118 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3449, 3067, 2978, 2960, 1625, 1461, 1426, 1364, 1274, 1115, 770 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.43 (dd, J = 7.6, 1.2 Hz, 1 H), 8.18 (dd, J = 8.4, 1.2 Hz, 1 H), 8.02 (d, J = 8.4 Hz, 1 H), 7.98 (d, J = 7.6 Hz, 1 H), 7.81–7.77 (m, 1 H), 7.69–7.65 (m, 1 H), 6.74 (s, 1 H), 2.85–2.81 (m, 2 H), 1.82–1.72 (m, 2 H), 1.09 (t, J = 7.6 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.3, 134.1, 134.0, 132.7, 131.7, 128.1, 126.7, 126.4, 125.7, 124.3, 124.0, 122.6, 36.3, 22.0, 14.0.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₄O₂SNa: 281.0607; found: 281.0598.

3-Butylbenzo[de]thiochromene 1,1-Dioxide (3f)

Yield: 41.9 mg (77%); white solid; mp 85–86 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3444, 3383, 2952, 2930, 2871, 1628, 1468, 1275, 1116, 1050, 760 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.42 (dd, J = 7.6, 1.2 Hz, 1 H), 8.17 (dd, J = 8.4, 1.2 Hz, 1 H), 8.01 (d, J = 8.4 Hz, 1 H), 7.98 (d, J = 7.4 Hz, 1 H), 7.80–7.77 (m, 1 H), 7.69–7.65 (m, 1 H), 6.74 (s, 1 H), 2.85 (t, J = 7.2 Hz, 2 H), 1.75–1.67 (m, 2 H), 1.55–1.46 (m, 2 H), 0.98 (t, J = 7.6 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.5, 134.1, 134.0, 132.7, 131.7, 128.1, 126.7, 126.4, 125.6, 124.3, 124.0, 122.5, 34.1, 31.0, 22.6, 13.9.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₇O₂S: 273.0944; found: 273.0945.

3-(Cyclohexylmethyl)benzo[de]thiochromene 1,1-Dioxide (3g)

Yield: 37.4 mg (60%); orange solid; mp 151–152 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3071, 3041, 2921, 1625, 1583, 1466, 1339, 1158, 1081 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.43 (d, J = 7.6 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 8.02 (d, J = 8 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 1 H), 7.81–7.77 (m, 1 H), 7.70–7.65 (m, 1 H), 6.68 (s, 1 H), 2.69 (d, J = 6.8 Hz, 2 H), 1.84 (d, J = 12.4 Hz, 2 H), 1.73–1.62 (m, 5 H), 1.21–1.16 (m, 2 H), 1.09–1.00 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.7, 134.2, 134.0, 132.7, 131.8, 128.5, 126.7, 126.4, 125.7, 124.3, 124.1, 123.5, 42.7, 37.6, 33.5, 26.2, 26.1.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₂₁O₂S: 313.1257; found: 313.1265.

3-(Cyclopropyl)benzo[de]thiochromene 1,1-Dioxide (3h)

Yield: 18.9 mg (37%); white solid; mp 163–164 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3071, 3042, 3005, 2922, 1626, 1584, 1464, 1430, 1344, 1158 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.42 (d, J = 7.6 Hz, 2 H), 8.18 (d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.81–7.77 (m, 1 H), 7.72–7.69 (m, 1 H), 6.70 (s, 1 H), 2.19–2.12 (m, 1 H), 1.15–1.10 (m, 2 H), 0.87–0.81 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 126.3, 134.0, 133.9, 132.5, 131.7, 128.9, 126.8, 126.4, 125.5, 125.2, 124.1, 121.7, 15.4, 6.7.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₂O₂SNa: 279.0450; found: 279.0445.

3-(tert-Butyl)benzo[de]thiochromene 1,1-Dioxide (3i)

Yield: 24.7 mg (45%); yellow solid; mp 158–159 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3065, 2966, 2923, 1620, 1462, 1339, 1153 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.45–8.41 (m, 2 H), 8.18 (dd, J = 8.0, 1.2 Hz, 1 H), 8.01 (d, J = 8.0 Hz, 1 H), 7.79–7.76 (m, 1 H), 7.69–7.65 (m, 1 H), 6.88 (s, 1 H), 1.57 (s, 9 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.1, 134.5, 133.2, 133.0, 131.5, 131.2, 126.0, 125.9, 125.5, 125.2, 123.1, 122.3, 37.7, 31.7.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₇O₂S: 273.0944; found: 273.0939.

3-(2-Bromoethyl)benzo[de]thiochromene 1,1-Dioxide (3j)

Yield: 49.5 mg (76%); white solid; mp 174–175 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3045, 3033, 2921, 2852, 1627, 1584, 1454, 1306, 1153, 627 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.46 (dd, J = 7.2, 1.2 Hz, 1 H), 8.22 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 7.95 (d, J = 7.2 Hz, 1 H), 7.86–7.83 (m, 1 H), 7.74–7.70 (m, 1 H), 6.83 (s, 1 H), 3.68 (t, J = 7.2 Hz, 2 H), 3.43 (t, J = 7.6 Hz, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 141.7, 134.2, 134.0, 132.8, 132.3, 127.7, 126.8, 126.7, 126.0, 124.6, 124.2, 123.1, 37.4, 29.0.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₁BrO₂SNa: 344.9555; found: 344.9548.

3-(3-Chloropropyl)benzo[de]thiochromene 1,1-Dioxide (3k)

Yield: 49.6 mg (85%); white solid; mp 128–129 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3069, 3042, 2921, 1626, 1584, 1454, 1329, 1156, 828, 759 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.45 (dd, J = 7.2, 1.2 Hz, 1 H), 8.21 (dd, J = 8.0, 1.2 Hz, 1 H), 8.04 (dd, J = 11.6, 8.4 Hz, 2 H), 7.84–7.80 (m, 1 H), 7.72–7.89 (m, 1 H), 6.79 (s, 1 H), 3.70 (t, J = 6.0 Hz, 2 H), 3.07 (t, J = 7.6 Hz, 2 H), 2.25–2.18 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.9, 134.1, 134.1, 132.7, 132.0, 128.1, 126.7, 126.6, 125.9, 124.3, 123.6, 123.4, 44.1, 31.6, 31.5.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₃ClO₂SNa: 315.0217; found: 315.0221.

3-(4-Iodobutyl)benzo[de]thiochromene 1,1-Dioxide (3l)

Yield: 49.7 mg (62%); yellow solid; mp 104–105 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3049, 2958, 2923, 2856, 1627, 1461, 1339, 1311, 1154 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.43 (d, J = 7.6 Hz, 1 H), 8.19 (d, J = 8.4 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.99 (d, J = 7.6 Hz, 1 H), 7.83–7.78 (m, 1 H), 7.71–7.66 (m, 1 H), 6.75 (s, 1 H), 3.25 (t, J = 6.4 Hz, 2 H), 2.88 (t, J = 7.2 Hz, 2 H), 2.03–1.96 (m, 2 H), 1.90–1.83 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.7, 134.1, 132.7, 131.9, 128.1, 126.7, 126.5, 125.8, 124.3, 123.7, 122.9, 33.3, 32.8, 30.0, 5.9.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₅IO₂SNa: 420.9730; found: 420.9738.

3-(3-Hydroxypropyl)benzo[de]thiochromene 1,1-Dioxide (3m)

Yield: 24.7 mg (47%); yellow solid; mp 110–111 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3449, 3296, 3067, 2921, 1720, 1627, 1460, 1268, 1115, 1049, 760 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.42 (d, J = 6.8 Hz, 1 H), 8.17 (d, J = 8.0 Hz, 1 H), 8.03–7.99 (m, 2 H), 7.81–7.77 (m, 1 H), 7.67–7.63 (m, 1 H), 6.76 (s, 1 H), 3.78 (t, J = 6.0 Hz, 2 H), 2.97 (t, J = 7.6 Hz, 2 H), 1.99–1.92 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.2, 134.1, 134.0, 132.6, 131.9, 128.3, 126.8, 126.4, 125.7, 124.2, 123.8, 122.7, 61.5, 31.5, 30.7.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₄O₃SNa: 297.0556; found: 297.0544.

3-(2-(Benzyloxy)ethyl)benzo[de]thiochromene 1,1-Dioxide (3n)

Yield: 28.9 mg (41%); pink oil; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3057, 3032, 2923, 2859, 1627, 1454, 1331, 1279, 1156, 1116, 761 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.39 (d, J = 7.6 Hz, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.92 (d, J = 7.2 Hz, 1 H), 7.77–7.73 (m, 1 H), 7.61–7.57 (m, 1 H), 7.31–7.21 (m, 5 H), 6.78 (s, 1 H), 4.50 (s, 2 H), 3.78 (t, J = 6.4 Hz, 2 H), 3.12 (t, J = 6.8 Hz, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 142.3, 137.7, 134.1, 134.0, 132.6, 131.8, 128.5, 128.2, 127.8, 127.7, 126.7, 126.5, 125.7, 124.2, 124.0, 123.8, 73.3, 68.2, 34.5.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₈O₃SNa: 373.0869; found: 373.0877.

4-(1,1-Dioxidobenzo[de]thiochromen-3-yl)butyl But-2-ynoate (3o)

Yield: 24.4 mg (34%); pink solid; mp 135–136 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3331, 3046, 2960, 2924, 2243, 1701, 1628, 1457, 1316, 1261, 1156 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.44 (d, J = 7.6 Hz, 1 H), 8.19 (d, J = 8.0 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.97 (d, J = 7.2 Hz, 1 H), 7.83–7.79 (m, 1 H), 7.70–7.66 (m, 1 H), 6.76 (s, 1 H), 4.23 (t, J = 5.2 Hz, 2 H), 2.90 (t, J = 7.2 Hz, 2 H), 1.99 (s, 3 H), 1.87–1.84 (m, 4 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.7, 144.7, 134.1, 134.0, 132.7, 131.9, 128.0, 126.7, 126.5, 125.8, 124.3, 123.8, 122.9, 86.0, 72.3, 65.0, 33.8, 28.2, 25.2, 3.8.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₈O₄SNa: 377.0818; found: 377.0809.

Ethyl Benzo[de]thiochromene-3-carboxylate 1,1-Dioxide (3p)

Yield: 20.0 mg (37%); purple solid; mp 135–136 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3431, 3053, 3037, 2988, 1724, 1625, 1473, 1338, 1245, 1180, 759 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.45 (d, J = 7.2 Hz, 1 H), 8.40 (d, J = 7.6 Hz, 1 H), 8.23 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 7.86–7.82 (m, 1 H), 7.72–7.68 (m, 1 H), 7.36 (s, 1 H), 4.48 (q, J = 7.2 Hz, 2 H), 1.45 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 164.5, 136.4, 134.7, 133.3, 132.6, 132.5, 131.4, 127.8, 126.9, 126.7, 126.2, 123.9, 120.4, 62.8, 14.2.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₃O₄S: 289.0529; found: 289.0530.

2,3-Diethylbenzo[de]thiochromene 1,1-Dioxide (3q)

Yield: 19.1 mg (35%); yellow solid; mp 154–155 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3676, 3053, 1624, 1452, 1339, 1167, 775 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.42 (dd, J = 7.6, 1.2 Hz, 1 H), 8.14 (dd, J = 8.0, 0.8 Hz, 1 H), 7.95 (d, J = 2.0 Hz, 1 H), 7.93 (d, J = 1.6 Hz, 1 H), 7.78–7.74 (m, 1 H), 7.68–7.64 (m, 1 H), 2.95–2.89 (m, 4 H), 1.45 (t, J = 7.6 Hz, 3 H), 1.33 (t, J = 7.6 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 141.3, 136.6, 133.7, 133.5, 132.6, 130.4, 127.6, 126.9, 126.2, 125.4, 124.3, 124.2, 22.6, 19.1, 15.5, 14.5.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₆O₂SNa: 295.0763; found: 295.0757.

Ethyl 3-Phenylbenzo[de]thiochromene-2-carboxylate 1,1-Dioxide (3r)

Yield: 38.6 mg (53%); yellow solid; mp 170–171 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3424, 3102, 3058, 1720, 1619, 1342, 1296, 1135, 1095, 763 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 7.6 Hz, 1 H), 8.24 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1 H), 7.87–7.83 (m, 1 H), 7.58–7.54 (m, 1 H), 7.51–7.43 (m, 4 H), 7.36–7.34 (m, 2 H), 4.14 (q, J = 7.2 Hz, 2 H), 1.03 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 160.9, 148.5, 135.9, 134.2, 134.2, 134.0, 133.0, 132.4, 130.6, 129.3, 129.3, 128.4, 126.9, 126.9, 125.9, 125.2, 124.0, 62.4, 13.7.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₁H₁₆O₄SNa: 387.0662; found: 387.0667.

3-Phenylbenzo[de]thiochromene 1,1-Dioxide (3s)

Yield: 14.6 mg (25%); yellow solid; mp 160–161 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3057, 2970, 2901, 1623, 1461, 1338, 1153, 749 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.51 (dd, J = 7.2, 1.2 Hz, 1 H), 8.24 (dd, J = 8.0, 1.2 Hz, 1 H), 8.05 (dd, J = 7.2, 2.8 Hz, 1 H), 7.88–7.85 (m, 1 H), 7.60–7.57 (m, 2 H), 7.53–7.50 (m, 3 H), 7.46–7.43 (m, 2 H), 6.80 (s, 1 H).

¹³C NMR (100 MHz, CDCl₃): δ = 146.9, 137.3, 134.3, 134.1, 132.6, 132.1, 132.0, 129.2, 129.1, 128.7, 126.7, 126.6, 125.9, 124.8, 124.1, 123.9.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₃O₂S: 293.0631; found: 293.0632.

3-(p-Tolyl)benzo[de]thiochromene 1,1-Dioxide (3t)

Yield: 10.6 mg (17%); yellow solid; mp 127–128 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3412, 3062, 2969, 2902, 1673, 1607, 1460, 1323, 1174, 1118, 830 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.51 (dd, J = 7.2, 1.2 Hz, 1 H), 8.24 (dd, J = 8.0, 1.2 Hz, 1 H), 8.04 (dd, J = 8.0, 1.2 Hz, 1 H), 7.88–7.84 (m, 1 H), 7.64–7.62 (m, 1 H), 7.59–7.55 (m, 1 H), 7.34–7.30 (m, 4 H), 6.78 (s, 1 H), 2.46 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 147.0, 139.3, 134.4, 134.3, 134.0, 132.6, 132.1, 131.9, 129.4, 129.0, 126.6, 126.6, 125.8, 124.9, 124.2, 123.6, 21.3.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₅O₂S: 307.0787; found: 307.0792.

3-(4-Nitrophenyl)benzo[de]thiochromene 1,1-Dioxide (3u)

Yield: 10.6 mg (16%); yellow solid; mp 233–234 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3042, 2986, 2972, 1623, 1522, 1457, 1349, 1324, 1170, 1121, 847 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.53 (d, J = 7.6 Hz, 1 H), 8.40 (d, J = 8.0 Hz, 2 H), 8.28 (d, J = 8.4 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.93–7.89 (m, 1 H), 7.65 (d, J = 8.4 Hz, 2 H), 7.62–7.58 (m, 1 H), 7.43 (d, J = 7.2 Hz, 1 H), 6.82 (s, 1 H).

¹³C NMR (100 MHz, CDCl₃): δ = 148.4, 144.7, 143.6, 134.4, 134.1, 132.7, 132.6, 131.6, 130.2, 127.1, 126.7, 126.3, 124.9, 124.1, 123.9, 123.9.

HRMS (EI): m/z [M]⁺ calcd for C₁₈H₁₁NO₄S: 337.0409; found: 337.0414.

7-(Dimethylamino)-3-(1-hydroxy-1-phenylethyl)benzo[de]thiochromene 1,1-Dioxide (3v)

Yield: 45.2 mg (60%); yellow solid; mp 80–81 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3451, 3053, 2925, 2900, 2792, 1614, 1460, 1336, 1154 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.48 (d, J = 8.4 Hz, 1 H), 8.43 (d, J = 7.2 Hz, 1 H), 7.72–7.68 (m, 2 H), 7.53–7.51 (m, 2 H), 7.35–7.23 (m, 5 H), 6.78 (d, J = 8.4 Hz, 1 H), 2.90 (s, 6 H), 2.63 (br s, 1 H), 1.97 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.8, 149.2, 145.8, 133.9, 133.4, 130.8, 129.0, 127.8, 127.3, 126.8, 125.4, 124.9, 124.5, 120.1, 115.0, 113.0, 53.4, 44.9, 31.3.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₁NO₃SNa: 402.1134; found: 402.1134.

7-Bromo-3-(1-hydroxy-1-phenylethyl)benzo[de]thiochromene 1,1-Dioxide (3w)

Yield: 63.7 mg (77%); white solid; mp 144–145 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3466, 3060, 3028, 2979, 2854, 1617, 1493, 1395, 1119, 758 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.32 (dd, J = 8.8 Hz, 1 H), 8.24 (d, J = 8.0Hz, 1 H), 8.06 (d, J = 8.0 Hz, 1 H), 7.93 (d, J = 7.6 Hz, 1 H), 7.51–7.48 (m, 3 H), 7.44–7.40 (m, 1 H), 7.36–7.32 (m, 2 H),7.30–7.27 (m, 1 H), 2.74 (s, 1 H), 2.00 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 149.0, 145.3, 133.8, 132.7, 131.4, 130.5, 130.5, 130.4, 129.1, 128.0, 127.4, 126.1, 125.5, 124.7, 123.5, 122.2, 76.9, 31.5.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₅BrO₃SNa: 436.9817; found: 436.9822.

7-Ethyl-3-(1-hydroxy-1-phenylethyl)benzo[de]thiochromene 1,1-Dioxide (3x)

Yield: 55.6 mg (76%); yellow solid; mp 82–83 °C; purification by flash column chromatography (eluent: EtOAc/petroleum ether 1:3).

IR: 3453, 3060, 2971, 2875, 1617, 1573, 1508, 1492, 1447, 1116, 760 cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 8.38 (d, J = 7.6 Hz, 1 H), 8.11 (d, J = 8.4 Hz, 1 H), 7.86 (d, J = 7.6 Hz, 1 H), 7.63 (d, J = 7.6 Hz, 1 H), 7.52–7.50 (m, 2 H), 7.47 (s, 1 H), 7.37–7.27 (m, 4 H), 3.17 (q, J = 7.6 Hz, 2 H), 2.73 (s, 1 H), 1.99 (s, 3 H), 1.36 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 149.3, 148.2, 145.6, 132.6, 131.1, 129.1, 127.9, 127.0, 125.8, 125.6, 125.5, 124.9, 123.3, 122.3, 76.8, 31.3, 26.8, 15.3.

HRMS (EI): m/z [M]⁺ calcd for C₂₂H₂₀O₃S: 364.1133; found: 364.1135.

Conflict of Interest

The authors declare no conflict of interest.

• References

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• 7 CCDC 2214299 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
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Corresponding Author

Publication History

Received: 20 December 2022

Accepted after revision: 26 January 2023

Accepted Manuscript online:
26 January 2023

Article published online:
02 March 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1a Castán JM. A, Dalinot C, Dayneko S, Galan LA, Marqués PS, Alévêque O, Allain M, Maury O, Favereau L, Blanchard P, Welch GC, Cabanetos C. Chem. Commun. 2020; 56: 10131
  CrossrefPubMedSearch in Google Scholar
• 1b Galán LA, Castán JM. A, Dalinot C, Marqués PS, Blanchard P, Maury O, Cabanetos C, Bahers TL, Monnereau C. Phys. Chem. Chem. Phys. 2020; 22: 12373
  CrossrefPubMedSearch in Google Scholar
• 1c Zhang S, Chen Y, Liu Z, Fang Q. J. Photochem. Photobiol., A 2015; 311: 25
  CrossrefSearch in Google Scholar
• 2 Si E, Zhao P, Wang L, Duan Z, Mathey F. Eur. J. Org. Chem. 2020; 697
  Crossref
• 3a Muriel B, Waser J. Angew. Chem. Int. Ed. 2021; 60: 4075
  CrossrefPubMedSearch in Google Scholar
• 3b Yao Q, Kong L, Wang M, Yuan Y, Sun R, Li Y. Org. Lett. 2018; 20: 1744
  CrossrefPubMedSearch in Google Scholar
• 3c Yu Q, Zhang J, Wu F, Liu X, Wang C, Zhang J, Rong L. J. Org. Chem. 2022; 87: 7136
  CrossrefPubMedSearch in Google Scholar
• 3d Trogolo D, Maranzana A, Ghigo G, Tonachini G. Combust. Flame 2016; 168: 331
  CrossrefSearch in Google Scholar
• 4 Zeng X, Ilies L, Nakamura E. Org. Lett. 2012; 14: 954
  CrossrefPubMedSearch in Google Scholar
• 5 Domínguez AG, Müller S, Nevado C. Angew. Chem. Int. Ed. 2017; 56: 9949
  CrossrefPubMedSearch in Google Scholar
• 6a Liu Y, Song R, Li J. Sci. China Chem. 2016; 59: 161
  CrossrefSearch in Google Scholar
• 6b Sicignano M, Rodríguez RI, Alemán J. Eur. J. Org. Chem. 2021; 3303
  CrossrefPubMed
• 7 CCDC 2214299 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 8a Dixon IM, Collin JP, Sauvage JP, Flamigni L, Encinasb S, Barigelletti F. Chem. Soc. Rev. 2000; 29: 385
  CrossrefSearch in Google Scholar
• 8b Zhang P, Shi S, Gao X, Han S, Lin J, Zhao Y. Org. Biomol. Chem. 2019; 17: 2873
  CrossrefPubMedSearch in Google Scholar
• 9 Verhaegen Y, Liu L, Nguyen TT, Loy TV, Voet AR. D, Schols D, Dehaen W, Jonghe SD. Bioorg. Chem. 2021; 107: 104560
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material