N-Thiocyanatosaccharin: A 'Sweet' Electrophilic ... - ACS Publications

Abstract: N-Thiocyanatosaccharin. (R1) was readily prepared from the sweet additive Saccharin in two steps with 71% overall yield. Applying this new r...
0 downloads 0 Views 895KB Size
Download PDF
Note Cite This: J. Org. Chem. 2018, 83, 1576−1583

pubs.acs.org/joc

N‑Thiocyanatosaccharin: A “Sweet” Electrophilic Thiocyanation Reagent and the Synthetic Applications Di Wu, Jiashen Qiu, Pran Gopal Karmaker, Hongquan Yin,* and Fu-Xue Chen* School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No. 5 Zhongguancun Street, Haidian District, Beijing 100081, China S Supporting Information *

ABSTRACT: N-Thiocyanatosaccharin (R1) was readily prepared from the sweet additive Saccharin in two steps with a 71% overall yield. By applying this new reagent to diverse nucleophiles such as benzothiophenes, indoles, oxindoles, aromatic amines, phenols, β-keto carbonyl compounds, and aromatic ketones, a novel electrophilic thiocyanation reaction was achieved with high yields (up to 99%). The potential recycling of Saccharin, the wide scope of substrates, and the mild reaction conditions made this protocol much more practical.

T

mented the electrophilic thiocyanation of N-acyl imides with NTS (N-thiocyanatosuccinimide) (Scheme 1, entry 3).6 In 2014, Petrosyan reported the heteroarene thiocyanation through electrolysis.7 In 2015, Samareh and Kobra demonstrated the oxidant-free thiocyanation by AlCl3/NH4SCN.8 In 2015, Waser released the method of synthesizing thiocyanates from thiols (Scheme 1, entry 4).9 In spite of the above achievements, it remains challenging to find a more effective and widely applicable thiocyanation protocol. Herein, we report a new cationic thiocyanation reagent, Nthiocyanatosaccharin (R1), and its synthetic application in electrophilic thiocyanation reactions. It is conveniently synthesized from Saccharin in two sequential steps. The thiocyanations using R1 and various nucleophiles such as indoles, benzothiophenes, aromatic amines, β-keto carbonyl compounds, oxindoles, phenols, and aromatic ketones were achieved under mild reaction conditions with high yields (up to 99%). These results made R1 a general cationic thiocyanato reagent. The synthesis of N-thiocyanatosaccharin (R1) was shown in Scheme 2.10 Treatment of Saccharin with tert-butyl hypochlorite in methanol for 5 min gave N-chlorosaccharin with a yield of 80%, and then it reacted with AgSCN in CH2Cl2 for 30 min to afford R1. The structure of compound R1 was characterized by

hiocyano is an important functional group widely existing in bioactive natural products.1 It is a valuable synthetic intermediate to access sulfur-containing compounds.2a−h Their biological importance has stimulated the development of a new method to prepare organic thiocyanates. In the past decades, methodologies concerning oxidative thiocyanation of heterocycles or aromatics have been extensively studied (Scheme 1, Scheme 1. Thiocyanation Reactions

Scheme 2. Synthesis of R1

entry 1).3 To that end, thiocyanate salts (MSCN, M = Na+, K+, NH4+, etc.) were generally combinatory used with suitable oxidants such as CAN (ceric ammonium nitrate),3a NCS (Nchlorosuccinimide),3b−e DEAD (diethyl azodicarboxylate),3f oxone,3g oxygen,3h and DDQ (2,3-dichloro-5,6-dicyano-1,4benzoquinone).3i Alternatively, Cu-catalyzed cross-coupling was also employed to the synthesis of thiocyanates (Scheme 1, entry 2).4 In 1958, Angus demonstrated the thiocyanation of aromatic compounds using ClSCN.5 In 2008, Falck docu© 2018 American Chemical Society

Received: November 10, 2017 Published: January 5, 2018 1576

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry

reported. As shown in Table 2, a variety of β-keto carbonyl compounds including adamantyl esters, methyl esters, and

IR, HRMS, and 1H and 13C NMR. It can be prepared on a gram scale. A preliminary stability study revealed that R1 is sensitive to air and light, so it should be preserved in the dark at low temperatures under an argon atmosphere. With R1 in hand, we explored the reactions of R1 with many nucleophiles. As illustrated in Table 1, indoles with different

Table 2. Thiocyanation of β-Keto Carbonyl Compoundsa

Table 1. Thiocyanation Reactions of Indoles and Benzothiophenesa

Reaction conditions: β-keto carbonyl compounds (0.15 mmol), R1 (48 mg, 0.20 mmol, 1.3 equiv), THF (1.0 mL), rt, 12 h. bToluene (2.0 mL) instead of THF, DMAP (73 mg, 0.60 mmol, 4.0 equiv), 30 °C, 20 h. c37 °C. Ad = adamantyl. a

amides available in our lab were employed to react with R1, and the corresponding products (2a−2j) were isolated in good to excellent yields. The ring size and substituents did not affect the reaction efficiency of β-keto esters while the linear chain substrate (2j) was converted using DMAP as the base in toluene. The thiocyanation of oxindoles was also evaluated. As indicated in Table 3, the thiocyanation reaction of oxindoles

a Reaction conditions: indoles (0.15 mmol), R1 (48 mg, 0.20 mmol, 1.3 equiv), THF (1.0 mL), rt, 30 min. b3 h. c6 h. dTfOH (23 mg, 0.15 mmol, 1.0 equiv), CH3CN (1.0 mL) instead of THF. eZn(BF4)2·H2O (9 mg, 0.04 mmol, 0.20 equiv).

Table 3. Thiocyanation Reactions of Oxindolesa

substituents such as bromine, methoxyl, methyl, and nitro groups were tolerated under the standard conditions, providing the corresponding thiocyanated products in good to excellent yields with short reaction times at room temperature. The reaction completed quickly and cleanly. However, substrates with electron-withdrawing groups showed less activity with lower yields (1c, 1f, 1h). Reasonably, thiocyanation occurred at the 3-position of indoles, while thiocyanation took place at the 2-position to give the corresponding product (1b) in 98% yield when C-3 was occupied. The reaction is also suitable for a heterocyclic indole, and a moderate yield was obtained (1i, 74%). Moreover, benzothiophene was also efficiently converted into the corresponding thiocyanation product by R1 in an excellent yield (1j, 91%) when TfOH was utilized as the promoter.11 However, the N-Boc indole needed a Lewis acid to generate the desired product (1k) in a moderate yield. In the past few years, α-chlorination,12 α-azidation,13 αamination,14 and α-trifluoromethylthiolation15 of β-keto carbonyl compounds have been extensively studied. Our group discovered the α-cyanation reaction.16−18 In this paper, the α-thiocyanation of β-keto carbonyl compounds was

a

Reaction conditions: oxindoles (0.10 mmol), R1 (31 mg, 0.13 mmol, 1.3 equiv), THF (1.0 mL), rt, 12 h.

with R1 was carried out conveniently in THF at room temperature without any catalyst and additive, and all substrates were transformed to the corresponding products. The substituent on the phenyl ring was tolerated (3b−d), but unprotected amide N-H (3a) decreased the yield substantially. 1577

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry To widen the substrate scope of this new thiocyanato reagent, the electrophilic thiocyanations of anilines, phenols, and aromatic ketones with R1 were subsequently investigated. As shown in Table 4, most of the reactions between anilines

Table 5. Thiocyanation Reactions of Phenols and Derivativesa

Table 4. Thiocyanation Reaction of Aniline Derivativesa

a

Reaction conditions: phenols (0.20 mmol), R1 (48 mg, 0.20 mmol, 1.0 equiv), CH2Cl2 (1.0 mL), rt, 12 h.

Table 6. Thiocyanation Reaction of Aromatic Ketonesa

a

Reaction conditions: aniline (0.20 mmol), R1 (53 mg, 0.22 mmol, 1.1 equiv), CH2Cl2 (1.5 mL), rt, 12 h.

with R1 took place in high yields in CH2Cl2 at room temperature. However, the thiocyanation of anilines becomes a bit complicated since the thiocyanation exists in the oposition, p-position, and amino group. In most cases, the thiocyanation took place in the p-position to the amino group (4a−4e). When 3,5-dimethoxyaniline was used as the substrate to react with R1, the p-position substituted product (4f, 54%) and the o-position substituted product (4f′, 32%) were generated. With electron-withdrawing groups, the thiocyanation took place on the nitrogen of the amino group instead on the phenyl ring (5a−5c) in moderate to good yields. But in the case of the p-chloroaniline substrate, a mixture of 4-chloro-Nthiocyanatoaniline (5d, 30%) and 4-chloro-2-thiocyanatoaniline (5d′, 36%) was produced. As shown in Table 5, the electrophilic thiocyanation of phenols (6a−6f) and anisole (6e) with R1 provided the corresponding products in good yields. Similarly, thiocyanation mainly occurred at the p-position. Unlike 4f and 4f′, thiocyanation of 3,5-dimethoxyphenol exclusively gave product 6f (89%). However, unlike anilines, phenols bearing electronwithdrawing groups gave no conversion by treatment with R1. As indicated in Table 6, linear and cyclic aryl ketones reacted with R1. However, all substrates gave the corresponding products with moderate yields (7a−7g, 42%−74%). Subsequently, a gram-scale reaction was carried out (Scheme 3). Without surprise, the reaction gave 1.17 g of 1c in 91% yield from 5-bromoindole (5.1 mmol). In this case, the starting

a

Reaction conditions: ketones (0.20 mmol), R1 (63 mg, 0.26 mmol, 1.3 equiv), Me3SiCl (0.20 mmol, 1.0 equiv), MeCN (1.0 mL), 80 °C, 6 h. bZn(BF4)2·H2O (9 mg, 0.04 mmol, 0.20 equiv) instead of Me3SiCl.

Scheme 3. Synthesis of 1c on a Gram Scale

material Saccharin was recycled with a good yield (85%) after a simple workup. (See the Supporting Information.) In summary, a new cationic thiocyanato reagent, Nthiocyanatosaccharin, was prepared and applied to the direct electrophilic thiocyanation of diverse nucleophiles. The readily available synthesis, and its broad capacity for thiocyanation reactions under mild reaction conditions, and the good to excellent yields all made N-thiocyanatosaccharin (R1) a novel cationic thiocyanation reagent. 1578

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry

■

1H) ppm; 13C NMR (100 MHz, DMSO-d6) δ 142.6, 140.0, 137.6, 127.4, 118.6, 114.9, 114.2, 112.4, 93.7 ppm; IR (KBr) ν 3354, 3111, 2162, 1581, 1523 cm−1. 4-Methyl-3-thiocyanato-1H-indole (1g): 6 eluent petroleum ether/ ethyl acetate (5:1, v/v), white solid (27 mg, 99%), mp 107−109 °C; 1 H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 7.47 (d, J = 2.9 Hz, 1H), 7.25 (d, J = 8.3 Hz, 1H), 7.17 (t, J = 7.3 Hz, 1H), 7.01 (d, J = 7.1 Hz, 1H), 2.95 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 136.4, 132.1, 130.9, 125.5, 123.9, 123.4, 113.4, 110.1, 91.9, 19.1 ppm; IR (KBr) ν 3319, 2154, 1583, 1502, 1433 cm−1. 4-Bromo-3-thiocyanato-1H-indole (1h): eluent petroleum ether/ ethyl acetate (2:1, v/v), white solid (36 mg, 95%), mp 144−146 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.33 (s, 1H), 8.11 (d, J = 3.2 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H) ppm; 13C NMR (100 MHz, DMSO-d6) δ 137.6, 136.0, 125.3, 124.2, 124.0, 113.3, 112.6, 112.1, 90.2 ppm; IR (KBr) ν 3296, 2169, 2150, 1610, 1565, 1504, 1402 cm−1; HRMS (ESI) m/z [M − H]− calcd for C9H4BrN2S 250.9284, found 250.9284. 3-Thiocyanato-1H-pyrrolo[2,3-b]pyridine (1i): 20 eluent petroleum ether/ethyl acetate (2:1, v/v), white solid (20 mg, 74%), mp 197−199 °C; 1H NMR (400 MHz, DMSO-d6) δ 12.60 (s, 1H), 8.40 (d, J = 3.9 Hz, 1H), 8.14 (s, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.30 (dd, J = 7.9, 3.9 Hz, 1H) ppm; 13C NMR (175 MHz, DMSO-d6) δ 148.3, 144.4, 133.9, 126.4, 119.7, 117.3, 112.1, 88.9 ppm; IR (KBr) ν 2922, 2152, 1587 cm−1. 3-Thiocyanatobenzo[b]thiophene (1j): eluent petroleum ether, white solid (26 mg, 91%), mp 82−84 °C; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 5.6 Hz, 2H), 7.59−7.55 (m, 1H), 7.52−7.48 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 139.6, 137.3, 134.3, 125.9, 125.8, 123.3, 122.3, 112.1, 109.7 ppm; IR (KBr) ν 2154, 1869, 1655, 1554, 1508 cm−1. Anal. Calcd for C9H5NS2: C, 56.52; H, 2.64; N, 7.32. Found: C, 56.48; H, 2.63; N, 7.32. N-Boc-3-thiocyanato-1H-indole (1k): eluent petroleum ether/ethyl acetate (15:1, v/v), colorless liquid (30 mg, 73%); 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 7.6 Hz, 1H), 7.96 (s, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.47−7.39 (m, 2H), 1.69 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 148.4, 135.4, 131.7, 129.1, 126.0, 124.0, 119.1, 115.7, 110.1, 99.1, 85.4, 28.1 ppm; IR (KBr) ν 2982, 2926, 2850, 2158, 2005, 1748, 1531 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C14H18N3O2S 292.1114, found 292.1115. Procedure for the Thiocyanation of β-Keto Carbonyl Compounds. β-Keto carbonyl compounds (0.15 mmol) and R1 (48 mg, 0.20 mmol, 1.3 equiv) were stirred in THF (1.0 mL) for 12 h at room temperature. After the reaction was completed (monitored by TLC), the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired product. Adamantyl 1-Oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carboxylate (2a): eluent petroleum ether/ethyl acetate (10:1, v/v), white solid (50 mg, 88%), mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.9 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 3.18−3.10 (m, 3H), 2.60−2.53 (m, 1H), 2.15 (s, 3H), 2.05 (s, 6H), 1.62 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 189.6, 165.1, 142.6, 134.8, 130.6, 128.9, 128.2, 127.5, 110.6, 85.5, 66.4, 40.9, 35.9, 34.1, 30.9, 27.1 ppm; IR (KBr) ν 2912, 2852, 2156, 1724, 1688, 1599 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C22H27N2O3S 399.1737, found 399.1745. Adamantyl 7-Methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carboxylate (2b): eluent petroleum ether/ethyl acetate (15:1, v/v), white solid (59 mg, 95%), mp 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 2.6 Hz, 1H), 7.18 (d, J = 8.5 Hz, 1H), 7.13 (dd, J = 8.5, 2.6 Hz, 1H), 3.84 (s, 3H), 3.11−3.06 (m, 3H), 2.59−2.50 (m, 1H), 2.15 (s, 3H), 2.07 (s, 6H), 1.62 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 189.7, 165.3, 158.9, 135.3, 131.4, 130.2, 123.5, 110.7, 109.9, 85.6, 66.4, 55.7, 41.0, 36.0, 34.5, 31.0, 26.5 ppm; IR (KBr) ν 2912, 2852, 2156, 1724, 1685, 1610 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C23H26NO4S 412.1583, found 412.1582. Adamantyl 7-Bromo-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carboxylate (2c): eluent petroleum ether/ethyl

EXPERIMENTAL SECTION

General Experimental Information. All chemicals were bought from commercial companies and used directly unless noted. Reactions were carried out in a reaction tube with common solvents open to air. 1 H and 13C{1H} NMR spectra were recorded on a Bruker 400 or 700 instrument in CDCl3 and DMSO-d6. Chemical shifts are recorded in ppm. All of the MS of samples were analyzed on an Agilent (Q-TOF 6520) unit with an ESI source. All IR spectra were measured on a Shimadzu IRAffinnity-1s spectrometer. Melting points were measured on a digital micromelting point apparatus unless otherwise indicated. Melting points were measured on a DSC-60 under a nitrogen flow (50 mL/min) at a heating rate of 5 °C/min. Procedure for Synthesis of R1. Saccharin (3.0 g, 16.41 mmol) and tert-butyl hypochlorite (19.69 mmol, 1.2 equiv) were stirred in methanol (35.0 mL) for 5 min at room temperature. Then the suspension was filtered giving the N-chlorosaccharin with a yield of 80%. N-Chlorosaccharin (542 mg, 2.50 mmol) was treated with AgSCN (433 mg, 2.63 mmol, 1.05 equiv) in CH2Cl2 (25.0 mL) for 30 min at room temperature. Then the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the product R1 in 89% yield. N-Thiocyanatosaccharin (R1): white solid (535 mg, 89%), mp 227 °C (DSC, 10 °C/min, peak); 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 7.5 Hz, 1H), 8.03−7.93 (m, 3H) ppm; 13C NMR (175 MHz, CDCl3) δ 157.3, 138.1, 136.7, 135.3, 126.7, 126.2, 122.2, 108.2 ppm; IR (KBr) ν 2100, 1720, 1593, 1458 cm−1; HRMS (ESI) m/z [M − SCN]− calcd for C7H4NO3S 181.9917, found 181.9912. Procedure for the Thiocyanation of Indoles. Indoles (0.15 mmol) and R1 (48 mg, 0.20 mmol, 1.3 equiv) were stirred in THF (1.0 mL) for 30 min at room temperature. After the reaction was completed (monitored by TLC), the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired products (1a−1k). 3-Thiocyanato-1H-indole (1a): 3h eluent petroleum ether/ethyl acetate (2:1, v/v), pale yellow solid (26 mg, 98%), mp 72−74 °C; 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 7.82−7.80 (m, 1H), 7.50 (d, J = 2.5 Hz, 1H), 7.44−7.42 (m, 1H), 7.33−7.31 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 136.0, 131.0, 127.7, 123.9, 122.0, 118.8, 112.1, 112.0, 92.4 ppm; IR (KBr) ν 3286, 2160, 1614 cm−1. 3-Methyl-2-thiocyanato-1H-indole (1b): 19 eluent petroleum ether/ethyl acetate (20:1, v/v), white solid (28 mg, 98%), mp 86− 88 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.49 (d, J = 7.9 Hz, 1H), 7.24 (m, 2H), 7.18−7.13 (m, 1H), 2.33 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 141.2, 132.9, 127.5, 123.6, 120.5, 119.9, 118.9, 110.7, 109.6, 8.3 ppm; IR (KBr) ν 3377, 2106, 2044, 1456 cm−1. 5-Bromo-3-thiocyanato-1H-indole (1c): 3h eluent petroleum ether/ ethyl acetate (2:1, v/v), white solid (36 mg, 95%), mp 131−133 °C; 1 H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 7.92 (s, 1H), 7.51 (d, J = 2.2 Hz, 1H), 7.39 (dd, J = 8.7, 2.2 Hz, 1H), 7.29 (d, J = 8.7 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 134.7, 132.1, 129.4, 127.1, 121.5, 115.5, 113.6, 111.6, 92.2 ppm; IR (KBr) ν 3340, 3109, 2148, 1718, 1691 cm−1. 1-Methyl-3-thiocyanato-indole (1d): 3h eluent petroleum ether/ ethyl acetate (20:1, v/v), white solid (28 mg, 99%), mp 84−86 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.2 Hz, 1H), 7.32−7.18 (m, 4H), 3.74 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 137.2, 135.1, 128.5, 123.5, 121.7, 119.0, 111.9, 110.2, 90.0, 33.5 ppm; IR (KBr) ν 3120, 2150, 1610, 1514 cm−1. 5-Methoxy-3-thiocyanato-1H-indole (1e): 3h eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (30 mg, 98%), mp 119− 121 °C; 1H NMR (400 MHz, CDCl3) δ 8.71 (s, 1H), 7.45 (d, J = 2.9 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H), 7.19 (d, J = 2.4 Hz, 1H), 6.95 (dd, J = 8.9, 2.4 Hz, 1H), 3.91 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 155.7, 131.4, 130.8, 128.5, 114.5, 113.0, 112.0, 99.8, 91.4, 55.8 ppm; IR (KBr) ν 3286, 3134, 2154, 1622, 1568 cm−1. 5-Nitro-3-thiocyanato-1H-indole (1f): 3c eluent petroleum ether/ ethyl acetate (1:1, v/v), white solid (28 mg, 85%), mp 126−128 °C; 1 H NMR (400 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.53 (d, J = 2.2 Hz, 1H), 8.28 (s, 1H), 8.14 (dd, J = 9.2, 2.2 Hz, 1H), 7.72 (d, J = 9.2 Hz, 1579

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry acetate (20:1, v/v), white solid (54 mg, 78%), mp 134−136 °C; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.2 Hz, 1H), 7.66 (dd, J = 8.2, 2.2 Hz, 1H), 7.17 (d, J = 8.2 Hz, 1H), 3.13−3.07 (m, 3H), 2.59−2.51 (m, 1H), 2.16 (s, 3H), 2.06 (s, 6H), 1.62 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 188.4, 164.8, 141.3, 137.6, 132.1, 130.8, 130.7, 121.5, 110.2, 85.9, 65.9, 40.9, 35.9, 33.9, 30.9, 26.7 ppm; IR (KBr) ν 2912, 2852, 2156, 1728, 1693, 1589 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C22H23BrNO3S 460.0582, found 460.0587. Methyl 5-Methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carboxylate (2d): eluent petroleum ether/ethyl acetate (15:1, v/v), white solid (40 mg, 92%), mp 122−124 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.9 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.24−3.18 (m, 2H), 2.89−2.81 (m, 1H), 2.55−2.47 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 189.3, 166.8, 156.8, 131.9, 131.0, 128.0, 119.7, 115.7, 110.0, 65.5, 55.8, 54.1, 33.1, 21.2 ppm; IR (KBr) ν 2956, 2841, 2156, 1734, 1680, 1593 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C14H14NO4S 292.0638, found 292.0640. Methyl 1-Oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2carboxylate (2e): eluent petroleum ether/ethyl acetate (15:1, v/v), white solid (33 mg, 85%), mp 137−139 °C; 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 7.9 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 3.82 (s, 3H), 3.24−3.12 (m, 3H), 2.64−2.57 (m, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 189.0, 166.9, 142.9, 135.2, 130.1, 129.0, 128.6, 127.6, 110.0, 65.5, 54.2, 33.9, 26.9 ppm; IR (KBr) ν 2922, 2850, 2156, 1734, 1684 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C13H12NO3S 262.0532, found 262.0541. Adamantyl 1-Oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (2f): eluent petroleum ether/ethyl acetate (15:1, v/v), white solid (42 mg, 76%), mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.7 Hz, 1H), 7.74−7.70 (m, 1H), 7.53−7.47 (m, 2H), 4.05 (d, J = 18.0 Hz, 1H), 3.62 (d, J = 18.0 Hz, 1H), 2.16 (s, 3H), 2.05 (d, J = 3.0 Hz, 6H), 1.63 (d, J = 2.8 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 195.1, 164.8, 151.1, 136.7, 133.2, 128.8, 126.2, 125.8, 109.8, 86.2, 64.4, 40.9, 40.5, 35.8, 31.0 ppm; IR (KBr) ν 2912, 2850, 2156, 1732, 1716, 1450 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C21H25N2O3S 385.1586, found 385.1570. Adamantyl 5-Chloro-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (2g): eluent petroleum ether/ethyl acetate (15:1, v/v), white solid (57 mg, 95%), mp 140−142 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz, 1H), 7.51 (s, 1H), 7.46 (d, J = 8.2 Hz, 1H), 4.02 (d, J = 18.2 Hz, 1H), 3.59 (d, J = 18.2 Hz, 1H), 2.16 (s, 3H), 2.04 (d, J = 3.0 Hz, 6H), 1.62 (d, J = 2.6 Hz, 6H) ppm; 13 C NMR (100 MHz, CDCl3) δ 193.8, 164.4, 152.5, 143.6, 131.8, 129.8, 126.9, 126.5, 109.7, 86.6, 64.5, 41.0, 40.2, 35.9, 31.1 ppm; IR (KBr) ν 2914, 2852, 2156, 1739, 1597, 1456 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C21H24ClN2O3S 419.1196, found 419.1200. Adamantyl 6-Methyl-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxamide (2h): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (55 mg, 97%), mp 132−134 °C; 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 6.96 (s, 1H), 4.22 (d, J = 18.7 Hz, 1H), 3.18 (d, J = 18.7 Hz, 1H), 2.43 (s, 3H), 2.09 (s, 3H), 2.04 (d, J = 2.4 Hz, 6H), 1.68 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 198.4, 162.5, 148.0, 139.2, 138.7, 133.2, 126.3, 125.6, 109.0, 58.1, 53.3, 41.2, 37.1, 36.3, 29.5, 21.2 ppm; IR (KBr) ν 2908, 2848, 2153, 1709, 1682, 1531, 1456 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C22H25N2O2S 381.1637, found 381.1630. Adamantyl 5-Oxo-6-thiocyanato-6,7,8,9-tetrahydro-5H-benzo[7]annulene-6-carboxylate (2i): eluent petroleum ether/ethyl acetate (15:1, v/v), colorless oil (55 mg, 96%); 1H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 7.6, 0.8 Hz, 1H), 7.45−7.41 (m, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 3.04−2.97 (m, 2H), 2.93−2.86 (m, 1H), 2.33−2.26 (m, 1H), 2.18−2.02 (m, 5H), 1.89 (m, 6H), 1.57 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 197.6, 164.7, 139.7, 136.7, 132.5, 130.7, 129.9, 126.6, 110.8, 84.9, 72.2, 40.6, 35.9, 33.9, 30.8, 26.9, 24.9 ppm; IR (KBr) ν 2912, 2852, 2154, 1737, 1682, 1597 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C23H26NO3S 396.1628, found 396.1635.

Ethyl 2-Methyl-3-oxo-3-phenyl-2-thiocyanatopropanoate (2j): 23 eluent petroleum ether/ethyl acetate (10:1, v/v), colorless oil (34 mg, 87%); 1H NMR (400 MHz, CDCl3) δ 7.87−7.85 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 8.0 Hz, 2H), 4.33−4.23 (m, 2H), 2.14 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 190.4, 168.2, 134.4, 132.3, 129.2, 129.0, 110.1, 67.5, 63.8, 23.9, 13.7 ppm; IR (KBr) ν 2928, 2156, 1737, 1674, 1597 cm−1. Procedure for the Thiocyanation of Oxindoles. Oxindoles (0.10 mmol) and R1 (31 mg, 0.13 mmol, 1.3 equiv) were stirred in THF (1.0 mL) for 12 h at room temperature. After the reaction was completed (monitored by TLC), the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired product. 3-Thiocyanato-3-(p-tolyl)indolin-2-one (3a): eluent petroleum ether/ethyl acetate (2:1, v/v), yellow solid (14 mg, 48%), mp 98− 100 °C; 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 11.3 Hz, 1H), 7.38−7.34 (m, 1H), 7.27 (d, J = 9.2 Hz, 1H), 7.23 (d, J = 8.3 Hz, 2H), 7.18−7.11 (m, 3H), 6.99 (d, J = 7.8 Hz, 1H), 2.33 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 174.1, 140.2, 139.7, 139.2, 133.4, 130.7, 129.7, 129.3, 125.7, 125.2, 124.0, 111.1, 69.4, 21.1 ppm; IR (KBr) ν 3165, 2033, 1726, 1617 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C16H16N3OS 298.1009, found 298.1009. 1-Benzyl-3-phenyl-3-thiocyanatoindolin-2-one (3b): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (33 mg, 91%), mp 128−130 °C; 1H NMR (400 MHz, CDCl3) δ 7.65−7.63 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.46−7.40 (m, 3H), 7.35−7.28 (m, 6H), 7.21 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.9 Hz, 1H), 4.99 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 172.8, 142.2, 134.6, 133.4, 130.8, 129.5, 129.2, 128.9, 127.9, 127.8, 127.2, 127.0, 126.1, 123.8, 110.3, 109.3, 60.7, 44.6 ppm; IR (KBr) ν 2154, 1721, 1608, 1485 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C22H20N3OS 374.1322, found 374.1325. N-Boc-3-(4-methoxyphenyl)-2-oxo-3-thiocyanatoindoline (3c): eluent petroleum ether/ethyl acetate (15:1, v/v), pale yellow solid (31 mg, 80%), mp 107−109 °C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.2 Hz, 1H), 7.48 (t, J = 8.4 Hz, 1H), 7.36 (d, J = 7.4 Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 1.61 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 168.7, 159.4, 147.8, 139.4, 138.4, 129.8, 127.4, 126.8, 126.7, 126.0, 124.6, 124.5, 124.0, 114.8, 113.3, 84.4, 67.8, 54.4, 27.0 ppm; IR (KBr) ν 2978, 2927, 2027, 1789, 1732, 1606, 1506 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C21H20N2NaO4S 419.1036, found 419.1033. N-Boc-3-(4-methoxyphenyl)-5-methyl-2-oxo-3-thiocyanatoindoline-1-carboxylate (3d): eluent petroleum ether/ethyl acetate (5:1, v/ v), white solid (38 mg, 91%), mp 148−150 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 5.6 Hz, 1H), 7.22 (d, J = 8.7 Hz, 2H), 7.15 (s, 1H), 6.88 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 2.38 (s, 3H), 1.60 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 169.8, 160.3, 148.8, 140.0, 137.0, 135.5, 131.4, 128.6, 127.6, 127.0, 125.3, 115.5, 114.3, 85.1, 69.0, 55.4, 28.0, 21.1 ppm; IR (KBr) ν 2972, 2920, 2070, 1770, 1732, 1506 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C22H26N3O4S 428.1639, found 428.1642. Procedure for the Thiocyanation of Aniline Derivatives. Aniline derivatives (0.20 mmol) and R1 (53 mg, 0.22 mmol, 1.1 equiv) were stirred in CH2Cl2 (1.0 mL) for 12 h at room temperature. After the reaction was completed (monitored by TLC), the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired product. 4-Thiocyanatoaniline (4a): 3c eluent petroleum ether/ethyl acetate (10:1, v/v), yellow solid (29 mg, 96%), mp 47−49 °C; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 7.8 Hz, 2H), 6.66 (d, J = 7.8 Hz, 2H), 3.98 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 148.8, 134.4, 116.0, 112.4, 109.4 ppm; IR (KBr) ν 3419, 3346, 2147, 1888, 1595 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C7H7N2S 151.0324, found 151.0324. N,N-Dimethyl-4-thiocyanatoaniline (4b): 3h eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (31 mg, 87%), mp 66−68 °C; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 8.8 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 2.99 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 151.7, 134.5, 113.2, 112.7, 106.5, 40.2 ppm; IR (KBr) ν 2912, 2819, 1580

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry 2145, 1884, 1593, 1504 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C9H11N2S 179.0637, found 179.0635. 2,6-Diisopropyl-4-thiocyanatoaniline (4c): 21 eluent petroleum ether/ethyl acetate (15:1, v/v), colorless oil (37 mg, 74%); 1H NMR (400 MHz, CDCl3) δ 7.22 (s, 2H), 4.01 (s, 2H), 2.90−2.84 (m, 2H), 1.27 (d, J = 6.8 Hz, 12H) ppm; 13C NMR (100 MHz, CDCl3) δ 142.8, 134.0, 128.1, 112.8, 109.8, 28.1, 22.1 ppm; IR (KBr) ν 3402, 2958, 2924, 2150 cm−1. 2-Methyl-4-thiocyanatoaniline (4d): 4b eluent petroleum ether/ ethyl acetate (10:1, v/v), white solid (32 mg, 98%), mp 66−68 °C; 1H NMR (400 MHz, CDCl3) δ 7.27 (s, 1H), 7.26−7.23 (m, 1H), 6.66 (d, J = 8.2 Hz, 1H), 3.88 (s, 2H), 2.16 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 147.0, 135.1, 132.1, 123.9, 115.8, 112.5, 109.5, 17.2 ppm; IR (KBr) ν 3446, 3363, 2150, 1633 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C8H9N2S 165.0481, found 165.0478. 2-(tert-Butyl)-4-thiocyanatoaniline (4e): eluent petroleum ether/ ethyl acetate (10:1, v/v), yellowish oil (39 mg, 94%); 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 2.4 Hz, 1H), 7.25 (dd, J = 8.2, 2.4 Hz, 1H), 6.63 (d, J = 8.2 Hz, 1H), 4.13 (s, 2H), 1.41 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 147.1, 135.1, 132.1, 132.0, 118.7, 112.7, 109.6, 34.5, 29.3 ppm; IR (KBr) ν 3508, 3394, 3242, 2152, 1587, 1556 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C11H15N2S 207.0950, found 207.0942. 3,5-Dimethoxy-4-thiocyanatoaniline (4f): eluent petroleum ether/ ethyl acetate (5:1, v/v), white solid (27 mg, 54%), mp 170−172 °C; 1 H NMR (400 MHz, CDCl3) δ 5.89 (s, 2H), 4.01 (s, 2H), 3.86 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 161.7, 151.5, 112.5, 91.4, 86.0, 56.2 ppm; IR (KBr) ν 3362, 2920, 2848, 2150 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C9H11N2O2S 211.0536, found 211.0541. 3,5-Dimethoxy-2-thiocyanatoaniline (4f′): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (13 mg, 32%), mp 128− 130 °C; 1H NMR (400 MHz, CDCl3) δ 5.93 (d, 2.4 Hz, 1H, Ar−H), 5.92 (d, 2.4 Hz, 1H, Ar−H), 4.49 (s, 2H), 3.87 (s, 3H), 3.77 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 164.3, 161.8, 151.0, 111.1, 92.5, 90.0, 84.5, 56.2, 55.4 ppm; IR (KBr) ν 3412, 3323, 2953, 2924, 2142, 1614, 1585 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C9H11N2O2S 211.0536, found 211.0537. 4-(Thiocyanatoamino)benzonitrile (5a): eluent petroleum ether/ ethyl acetate (2:1, v/v), white solid (26 mg, 74%), mp 107−109 °C; 1 H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 5.75 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 147.4, 134.0, 118.7, 116.5, 112.2, 106.2 ppm; IR (KBr) ν 2224, 2147, 1645, 1604, 1506 cm−1; HRMS (ESI) m/z [M − H]− calcd for C8H4N3S 174.0131, found 174.0155. 4-(Thiocyanatoamino)bromobenzene (5b): eluent petroleum ether/ethyl acetate (10:1, v/v), white solid (35 mg, 76%), mp 64− 66 °C; 1H NMR (400 MHz, CDCl3) δ 7.46−7.43 (m, 2H), 7.01−6.97 (m, 2H), 5.19 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 142.6, 132.6, 118.2, 115.9, 112.9 ppm; IR (KBr) ν 2153, 2065, 1630 cm−1; HRMS (ESI) m/z [M + H]+ calcd for C7H6N2SBr 228.9430, found 228.9439. 4-(Thiocyanatoamino)fluorobenzene (5c): 3e eluent petroleum ether/ethyl acetate (2:1, v/v), white solid (17 mg, 51%), mp 77−79 °C; 1H NMR (400 MHz, CDCl3) δ 7.09−7.02 (m, 4H), 5.11 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 159.1 (d, J = 241.0 Hz), 139.5 (d, J = 2.6 Hz), 118.3 (d, J = 8.1 Hz), 116.3 (d, J = 22.9 Hz), 113.2 ppm; IR (KBr) ν 3267, 2149, 1635, 1506 cm−1. 4-(Thiocyanatoamino)chlorobenzene (5d): 3e eluent petroleum ether/ethyl acetate (5:1, v/v), colorless oil (12 mg, 30%); 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 5.16 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 142.0, 129.6, 128.5, 117.8, 112.8 ppm; IR (KBr) ν 2145, 1489 cm−1. 4-Chloro-2-thiocyanatoaniline (5d′): 28 eluent petroleum ether/ ethyl acetate (5:1, v/v), colorless oil (13 mg, 36%); 1H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.24 (d, J = 8.8 Hz, 1H), 6.75 (d, J = 8.8 Hz, 1H), 4.40 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 146.7, 134.8, 133.0, 123.3, 117.3, 109.3, 105.7 ppm; IR (KBr) ν 2152, 1611, 1537, 1473 cm−1.

Procedure for the Thiocyanation of Phenols. Phenols (0.20 mmol) and R1 (48 mg, 0.20 mmol, 1.0 equiv) were stirred in CH2Cl2 (1.0 mL) for 12 h at room temperature. After the reaction was completed (monitored by TLC), the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired product. 4-Thiocyanatophenol (6a): 22 eluent petroleum ether/ethyl acetate (5:1, v/v), yellowish oil (27 mg, 89%); 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 157.9, 134.2, 117.5, 113.6, 112.0; IR (KBr) ν 3368, 2158, 1598, 1583 cm−1. 2,6-Dimethyl-4-thiocyanatophenol (6b): 22 eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (26 mg, 73%), mp 97−99 °C; 1H NMR (400 MHz, CDCl3) δ 7.20 (s, 2H), 5.05 (s, 1H), 2.25 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 154.2, 132.4, 125.5, 112.6, 112.1, 15.8; IR (KBr) ν 3452, 2922, 2154, 1581, 1479 cm−1. 2-Methyl-4-thiocyanatophenol (6c): 22 eluent petroleum ether/ ethyl acetate (5:1, v/v), white solid (23 mg, 70%), mp 59−61 °C; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 2.2 Hz, 1H), 7.27 (dd, J = 8.4, 2.2 Hz, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.62 (s, 1H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.1, 135.0, 131.5, 126.8, 116.6, 113.0, 112.1, 15.7; IR (KBr) ν 3362, 2154, 1585, 1494 cm−1. 2-(tert-Butyl)-4-thiocyanatophenol (6d): 27 eluent petroleum ether/ethyl acetate (5:1, v/v), colorless oil (30 mg, 72%); 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 2.4 Hz, 1H), 7.28 (dd, J = 8.4, 2.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 1.40 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 156.7, 138.8, 131.7, 131.5, 118.2, 112.7, 112.4, 34.9, 29.1 ppm; IR (KBr) ν 3381, 2958, 2160, 1589, 1498 cm−1. 3-Methyl-4-thiocyanatophenol (6e): 22 eluent petroleum ether/ ethyl acetate (5:1, v/v), yellowish oil (29 mg, 88%); 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 6.0 Hz, 1H), 6.79 (d, J = 2.4 Hz, 1H), 6.71 (dd, J = 6.0, 2.4 Hz, 1H), 2.47 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 158.4, 143.3, 136.0, 118.6, 114.9, 112.6, 111.9, 20.9 ppm; IR (KBr) ν 3360, 2154, 1586, 1492 cm−1. 3,5-Dimethoxy-4-thiocyanatophenol (6f): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (38 mg, 89%), mp 158− 156 °C; 1H NMR (400 MHz, CDCl3) δ 6.10 (s, 2H), 3.85 (s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ 161.5, 160.8, 112.4, 92.8, 89.1, 56.3 ppm; IR (KBr) ν 3371, 2920, 2848, 2145, 1587, 1489 cm−1; HRMS (ESI) m/z [M + H]+ calcd C9H10NO3S 212.0376, found 212.0372. 1-Methoxy-2-methyl-4-thiocyanatobenzene (6g): 26 eluent petroleum ether/ethyl acetate (15:1, v/v), colorless oil (30 mg, 84%); 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.8 Hz, 1H), 7.34 (s, 1H), 6.84 (d, J = 8.8 Hz, 1H), 3.85 (s, 3H), 2.22 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 159.4, 134.2, 131.3, 129.4, 113.0, 111.8, 111.2, 55.5, 16.1 ppm; IR (KBr) ν 2924, 2848, 2154, 1591, 1490 cm−1. Procedure for the Thiocyanation of Aromatic Ketones. Aromatic ketones (0.20 mmol), Me3SiCl (0.20 mmol, 1.0 equiv), and R1 (63 mg, 0.26 mmol, 1.3 equiv) were stirred in MeCN (1.0 mL) for 6 h at 80 °C. Then the reaction mixture was purified by column chromatography on silica gel with petroleum ether/ethyl acetate to afford the pure desired product. 1-Phenyl-2-thiocyanatopropan-1-one (7a): 23 eluent petroleum ether/ethyl acetate (10:1, v/v), yellowish oil (25 mg, 66%); 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.6 Hz, 2H), 7.66 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.8 Hz, Hz, 2H), 5.08 (q, J = 7.2 Hz, 1H), 1.86 (d, J = 7.2 Hz, 3H); 13C NMR (175 MHz, CDCl3) δ 194.8, 134.5, 133.1, 129.2, 128.8, 111.4, 50.0, 19.8; IR (KBr) ν 2154, 1639, 1448 cm−1. 1-(4-Methoxyphenyl)-2-thiocyanatoethan-1-one (7b): 23 eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (20 mg, 48%), mp 93−95 °C; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 4.71 (s, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 189.1, 164.8, 130.9, 126.9, 114.4, 112.1, 55.7, 42.9; IR (KBr) ν 2158, 1645, 1506, cm−1. 2-Thiocyanato-2,3-dihydro-1H-inden-1-one (7c): 23 eluent petroleum ether/ethyl acetate (5:1, v/v), yellowish solid (28 mg, 74%), mp 84−86 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.52−7.45 (m, 2H), 4.13 (dd, J = 8, 4.4 Hz, 1H), 3.83 (dd, J = 17.6, 8 Hz, 1H), 3.36 (dd, J = 17.6, 4.4 Hz, 1H); 13C 1581

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

The Journal of Organic Chemistry

■

NMR (100 MHz, CDCl3) δ 198.0, 151.0, 136.4, 134.1, 128.6, 126.4, 125.0, 109.9, 48.2, 34.8; IR (KBr) ν 2154, 1635, 1463, 1431 cm−1. 5-Chloro-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7d): 24 eluent petroleum ether/ethyl acetate (10:1, v/v), yellowish solid (14 mg, 42%), mp 124−126 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.4 Hz, 1H), 7.51 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 4.12 (dd, J = 8.2, 4.0 Hz, 1H), 3.81 (dd, J = 18.0, 8.2 Hz, 1H), 3.36 (dd, J = 18.0, 4.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 196.5, 152.4, 143.3, 132.6, 129.6, 126.7, 126.2, 109.5, 48.1, 34.5; IR (KBr) ν 2156, 1714, 1633, 1519 cm−1. 6-Bromo-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7e): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (36 mg, 67%), mp 99−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 4.13 (dd, J = 8.0, 4.4 Hz, 1H), 3.78 (dd, J = 18.0, 8.0 Hz, 1H), 3.31 (dd, J = 18.0, 4.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 196.7, 149.6, 139.3, 135.9, 128.0, 127.9, 122.9, 109.5, 48.3, 34.5 ppm; IR (KBr) ν 2900, 2154, 1732, 1701, 1595 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C10H10BrN2OS 284.9692, found 284.9677. 5-Bromo-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7f): 25 eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (27 mg, 50%), mp 122−124 °C; 1H NMR (400 MHz, CDCl3) δ 7.71−7.69 (m, 2H), 7.62 (d, J = 8.0 Hz, 1H), 4.11 (dd, J = 8.0, 4.4 Hz, 1H), 3.82 (dd, J = 18.0, 8.0 Hz, 1H), 3.36 (dd, J = 18.0, 4.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 196.8, 152.4, 133.0, 132.4, 132.2, 129.8, 126.2, 109.5, 48.0, 34.4 ppm; IR (KBr) ν 2918, 2848, 2154, 1718, 1593, 1490 cm−1. 4-Bromo-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7g): eluent petroleum ether/ethyl acetate (5:1, v/v), white solid (30 mg, 57%), mp 90−92 °C; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.6 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 4.14 (dd, J = 8.0, 4.0 Hz, 1H), 3.78 (dd, J = 18.0, 8.0 Hz, 1H), 3.27 (dd, J = 18, 4.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 197.4, 150.8, 139.1, 136.1, 130.3, 123.8, 121.8, 109.4, 47.9, 35.7 ppm; IR (KBr) ν 2951, 2156, 1732, 1597, 1456 cm−1; HRMS (ESI) m/z [M + NH4]+ calcd for C10H10BrN2OS 284.9692, found 284.9679. Gram-Scale Reaction. 5-Bromo-1H-indole (1.0 g, 5.1 mmol) and R1 (1.6 g, 6.6 mmol, 1.3 equiv) were stirred in THF (30 mL) for 30 min at room temperature. Upon completion, the solvent was evaporated in a vacuum. CH2Cl2 (8.0 mL) was added to the residue, followed by sonic oscillation and filtration. The filtrate was flushed with CH2Cl2 (2.0 mL), and pure white Saccharin (1.03 g, 85%) was recovered. Then, the filtrate was concentrated under reduced pressure and purified by column chromatography on silica gel with petroleum ether/ethyl acetate as an eluent to afford product 1c (1.17 g, 91%).

■

REFERENCES

(1) Castanheiro, T.; Suffert, J.; Donnard, M.; Gulea, M. Chem. Soc. Rev. 2016, 45, 494. (2) (a) Zhang, Z.; Liebeskind, L. S. Org. Lett. 2006, 8, 4331. (b) Wu, F.-Y.; Li, Y.; Feng, H.; Wu, Q.; Jiang, B.; Shi, F.; Tu, S.-J. Synthesis 2011, 2011, 2459. (c) Wang, F.; Chen, C.; Deng, G.; Xi, C. J. Org. Chem. 2012, 77, 4148. (d) Demko, Z.-P.; Sharpless, K.-B. Org. Lett. 2001, 3, 4091. (e) Kamiya, I.; Kawakami, J.; Yano, S.; Nomoto, A.; Ogawa, A. Organometallics 2006, 25, 3562. (f) Lu, X.; Wang, H.; Gao, R.; Sun, D.; Bi, X. RSC Adv. 2014, 4, 28794. (g) Melzig, L.; Rauhut, C. B.; Naredi, R. N.; Knochel, P. Chem. - Eur. J. 2011, 17, 5362. (h) Pawliczek, M.; Garve, L. K. B.; Werz, D.-B. Org. Lett. 2015, 17, 1716. (3) (a) Nair, V.; George, T. G.; Nair, L. G.; Panicker, S. B. Tetrahedron Lett. 1999, 40, 1195. (b) Zhang, H.; Wei, Q.; Wei, S.; Qu, J.; Wang, B. Eur. J. Org. Chem. 2016, 2016, 3373. (c) Wang, C.; Wang, Z.; Wang, L.; Chen, Q.; He, M. Chin. J. Chem. 2016, 34, 1081. (d) Chen, Q.; Lei, Y.-J.; Wang, Y.-F.; Wang, C.; Wang, Y.-N.; Xu, Z.Q.; Wang, H.; Wang, R. Org. Chem. Front. 2017, 4, 369. (e) Xiong, H.Y.; Pannecoucke, X.; Besset, T. Org. Chem. Front. 2016, 3, 620. (f) Iranpoor, N.; Firouzabadi, H.; Khalili, D.; Shahin, R. Tetrahedron Lett. 2010, 51, 3508. (g) Wu, G.; Liu, Q.; Shen, Y.; Wu, W.; Wu, L. Tetrahedron Lett. 2005, 46, 5831. (h) Jiang, H.-F.; Yu, W.-T.; Tang, X.D.; Li, J.-X.; Wu, W.-Q. J. Org. Chem. 2017, 82, 9312. (i) Memarian, H.-R.; Mohammadpoor, B.-I.; Nikoofar, K. Ultrason. Sonochem. 2008, 15, 456. (4) (a) Beletskaya, I. P.; Sigeev, A.; Peregudov, A. S.; Petrovskii, P. V. Mendeleev Commun. 2006, 16, 250. (b) Sun, N.; Zhang, H.; Mo, W.; Shen, Z.; Hu, X. Synlett 2003, 96, 2214. (c) Yavari, I.; Damghani, T.; Nematpour, M. Helv. Chim. Acta 2013, 96, 2214. (d) Zhu, N.; Wang, F.; Chen, P.; Ye, J.; Liu, G. Org. Lett. 2015, 17, 3580. (5) Angus, A. B.; Bacon, R. G. R. J. Chem. Soc. 1958, 774. (6) Falck, J. K.; Gao, S.; Prasad, R. N.; Koduru, S. R. Bioorg. Med. Chem. Lett. 2008, 18, 1768. (7) Kokorekin, V. A.; Sigacheva, V. L.; Petrosyan, V. A. Tetrahedron Lett. 2014, 55, 4306. (8) Nikoofar, K.; Gorji, S. J. Sulfur Chem. 2016, 37, 80. (9) Frei, R.; Courant, T.; Wodrich, M. D.; Waser, J. Chem. - Eur. J. 2015, 21, 2662. (10) Xu, C.-F.; Ma, B.-Q.; Shen, Q.-L. Angew. Chem., Int. Ed. 2014, 53, 9316. (11) (a) Zhang, P.-P.; Li, M.; Xue, X.-S.; Xu, C.-F.; Zhao, Q.-C.; Liu, Y.-F.; Wang, H.-Y.; Guo, Y.-L.; Lu, L.; Shen, Q.-L. J. Org. Chem. 2016, 81, 7486. (b) Tung, P. T.; Zhong, C. Z.; Chien, T. C.; Yeh, M. C. J. Org. Chem. 2017, 82, 11543. (12) Qi, M.-H.; Wang, F.-J.; Shi, M. Tetrahedron: Asymmetry 2010, 21, 247. (13) Yasui, K.; Kojima, K.; Kato, T.; Odagi, M.; Kato, M.; Nagasawa, K. Tetrahedron 2016, 72, 5350. (14) Xiao, X.; Lin, L.-L.; Lian, X.-J.; Liu, X.-H.; Feng, X.-M. Org. Chem. Front. 2016, 3, 809. (15) Shao, X.-X.; Xu, C.-F.; Lu, L.; Shen, Q.-L. J. Org. Chem. 2015, 80, 3012. (16) Wang, Y.-F.; Qiu, J.-S.; Kong, D.-J.; Gao, Y.-T.; Lu, F.-P.; Karmaker, P. G.; Chen, F.-X. Org. Biomol. Chem. 2015, 13, 365. (17) Qiu, J.-S.; Wang, Y.-F.; Qi, G.-R.; Karmaker, P. G.; Yin, H.-Q.; Chen, F.-X. Chem. - Eur. J. 2017, 23, 1775. (18) Qiu, J.-S.; Wu, D.; Karmaker, P. G.; Qi, G.-R.; Chen, P.; Yin, H.Q.; Chen, F.-X. Org. Lett. 2017, 19, 4018. (19) Nikoofar, K.; Gorji, S. J. Sulfur Chem. 2015, 36, 178. (20) Yadav, J. S.; Reddy, B. V. S.; Reddy, Y. J. Chem. Lett. 2008, 37, 652. (21) Murthy, Y. L. N.; Govindh, B.; Diwakar, B. S.; Nagalakshmi, K.; Venu, R. J. Iran. Chem. Soc. 2011, 8, 292. (22) Mete, T. B.; Khopade, T. M.; Bhat, R. G. Tetrahedron Lett. 2017, 58, 415. (23) Meshram, H. M.; Thakur, P. B.; Babu, B. M.; Bangade, V. M. Tetrahedron Lett. 2012, 53, 1780.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02850. Optimizing conditions, DSC for R1, and copies of 1H and 13 C NMR (PDF)

■

Note

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Fu-Xue Chen: 0000-0002-9091-2147 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The financial support from the Natural Science Foundation of China (21572020) is acknowledged. 1582

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583

Note

The Journal of Organic Chemistry (24) Anil, K. M.; Reddy, K. R.; Reddy, M. V.; Reddy, C. S.; Reddy, C. D. Synth. Commun. 2008, 38, 2089. (25) Yu, L.; Wu, X.-Y.; Kim, M. J.; Vaithiyanathan, V.; Liu, Y.-D.; Tan, Y.; Qin, W.-L.; Song, C.-E.; Yan, H.-L. Adv. Synth. Catal. 2017, 359, 1879. (26) Venkanna, P.; Rajanna, K. C.; Kumar, M. S.; Venkateswarlu, M.; Ali, M. Synlett 2016, 27, 237. (27) Ciocoiu, C. C.; Ravna, A. W.; Sylte, I.; Hansen, T. V. Arch. Pharm. 2010, 343, 612. (28) Malik, J. K.; Noolvi, M. N.; Manvi, F. V.; Nanjwade, B. K.; Patel, H. M.; Manjula, S. N.; Mallokarjuna, R. C.; Barve, A. Lett. Drug Des. Discovery 2011, 8, 717.

1583

DOI: 10.1021/acs.joc.7b02850 J. Org. Chem. 2018, 83, 1576−1583