N-Thiocyanatosaccharin: A 'Sweet' Electrophilic Thiocyanation

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N-Thiocyanatosaccharin: A ‘Sweet’ Electrophilic Thiocyanation Reagent and the Synthetic Applications Di Wu, Jiashen Qiu, Pran Gopal Karmaker, Hongquan Yin, and Fu-Xue Chen J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02850 • Publication Date (Web): 05 Jan 2018 Downloaded from http://pubs.acs.org on January 5, 2018

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The Journal of Organic Chemistry

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.

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

T

hiocyano is an important functional group widely existing in bioactive natural products.1 It is of valuable synthetic intermediate to access sulfur-containing compounds.2a-h Their biological importance has stimulated the development of new method to prepare organic thiocyanates. In the last decades, methodologies concerning oxidative thiocyanation of heterocycles or aromatics have been extensively studied (Scheme 1, 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 (N-chlorosuccinimide),3b-e DEAD (diethyl azodicarboxylate),3f oxone,3g oxygen,3h and DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone).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 documented the electrophilic thiocyanation of N-acyl imides with NTS (N-thiocyanatosuccinimide) (Scheme 1, entry 3).6 In 2014, Petrosyan reported the heteroarene 7 thiocyanation through electrolysis. In 2015, Samareh and Kobra demonstrated the oxidant-free 8 thiocyanation by AlCl3/NH4SCN. In 2015, Waser

released the method of synthesis thiocyanates from thiols (Scheme 1, entry 4).9 In spite of the above achievements, it remains challenging to find a more effective, widely applicable thiocyanation protocol. Scheme 1 Thiocyanation reactions

Herein, we report a new cationic thiocyanation reagent, N-thiocyanatosaccharin (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,

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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 IR, HRMS, 1H and 13C NMR. It can be prepared on gram scale. Preliminary stability study revealed R1 is sensitive to air and light so it should be preserved in dark at low temperature under argon atmosphere.

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α-amination,14 and α-triﬂuoromethylthiolation15 of β-keto carbonyl compounds have been extensively studied. Our group discovered the α-cyanation reaction.16,17,18 In this paper, the α-thiocyanation of β-keto carbonyl compounds was reported. As shown in Table 2, a variety of β-keto carbonyl compounds including adamantyl esters, methyl esters and 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. Table

1

Thiocyanation

reactions

of

indoles

and

benzothiophenesa

Scheme 2 Synthesis of R1

With R1 in hand, we explored the reactions of R1 with many nucleophiles. As illustrated in Table 1, indoles with different 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 heterocyclic indole and a moderate yield was obtained (1i, 74%). Moreover, benzothiophene was also efficiently converted into the corresponding thiocyanation product by R1 in excellent yield (1j, 91%) when TfOH was utilized as the promotor.11 However, the N-Boc indole needed Lewis acid to generate the desired product (1k) in moderate yield. In the last few years, α-chlorination,12 α-azidation,13

a

Reaction conditions: indoles (0.15 mmol), R1 (48 mg, 0.20 mmol, 1.3

equiv), THF (1.0 mL), rt, 30 min. b 3 h, c 6 h, d TfOH (23 mg, 0.15 mmol, 1.0 equiv), CH3CN (1.0 mL) instead of THF, e Zn(BF4)2•H2O (9 mg, 0.04 mmol, 0.20 equiv).

Table 2 Thiocyanation of β-keto carbonyl compoundsa


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a


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. b Toluene (2.0 mL) instead of THF, DMAP (73 mg, 0.60 mmol, 4.0 equiv), 30 oC, 20 h. c 37 oC. Ad =

of anilines, phenols and aromatic ketones with R1 were subsequently investigated. As shown in Table 4, most of the reactions between anilines with R1 took place in high yields in CH2Cl2 at room temperature. However, the thiocyanation of anilines becomes a bit complicated since the thiocyanation exist in the o-position, p-position and amino group. In most cases, the thiocyanation took place in the p-position to 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 nitrogen of amino group instead on the phenyl ring (5a-5c) in moderate to good yields. But in the case of p-chloroaniline substrate, a mixture of 4-chloro-N-thiocyanatoaniline (5d, 30%) and 4-chloro-2-thiocyanatoaniline (5d', 36%) was produced.

adamantyl.

Table 4 Thiocyanation reaction of aniline derivativesa Table 3 Thiocyanation reactions of oxindolesa

a

Reaction conditions: oxindoles (0.10 mmol), R1 (31 mg, 0.13 mmol, 1.3

equiv), THF (1.0 mL), rt, 12 h.

The thiocyanation of oxindoles was also evaluated. As indicated in Table 3, the thiocyanation reaction of oxindoles 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. Substituent on the phenyl ring was tolerated (3b-d) but unprotected amide N-H (3a) decreased the yield substantially. To widen the substrate scope of this new thiocyanato reagent, the electrophilic thiocyanations

a

Reaction conditions: aniline (0.20 mmol), R1 (53 mg, 0.22 mmol, 1.1

equiv), CH2Cl2 (1.5 mL), rt, 12 h.

Table 5 Thiocyanation reactions of phenols and derivativesa



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Zn(BF4)2•H2O (9 mg, 0.04 mmol, 0.20 equiv) instead of Me3SiCl.

Subsequently, gram-scale reaction was carried out (Scheme 3). Without surprising, the reaction gave 1.17 g of 1c in 91% yield from 5-bromoindole (5.1 mmol). In this case, the starting material Saccharin was recycled with a good yield (85%) after a simple workup (see supporting information). Scheme 3 Synthesis of 1c on gram scale.

a

Reaction conditions: phenols (0.20 mmol), R1 (48 mg, 0.20 mmol, 1.0

equiv), CH2Cl2 (1.0 mL), rt, 12 h.

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 p-position. Unlike 4f and 4f', thiocyanation of 3,5-dimethoxyphenol exclusively gave product 6f (89%). However, unlike anilines, phenols bearing electron-withdrawing groups gave no conversion on 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%).

In summary, a new cationic thiocyanato reagent, N-thiocyanatosaccharin, was prepared and applied to the direct electrophilic thiocyanation of diverse nucleophiles. The readily 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.

█ EXPERIMENTAL SECTION General experimental information: All chemicals were bought from commercial companies and used direct unless noted. Reactions were carried out in reaction tube with common solvents open to air. 1H 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 the MS of samples were analyzed on an Agilent (Q-TOF 6520) with an

Table 6 Thiocyanation reaction of aromatic ketonesa

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 DSC-60 under a nitrogen flow (50 mL/min) at a heating rate of 5 oC/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 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 oC, 6 h.

b

CH2Cl2 (25.0 mL) for 30 min at room temperature. Then the reaction mixture was filtered and the filtrate was concentrated


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under reduced pressure to afford the product R1 in 89% yield.

5-Methoxy-3-thiocyanato-1H-indole (1e):3h Eluent petroleum

N-Thiocyanatosaccharin (R1): white solid (535 mg, 89%), mp

ether/ethyl acetate (5:1, V/V), white solid (30 mg, 98%), mp

NMR (400 MHz,

119–121 oC. 1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 1H),

DMSO-d6): δ = 8.17 (d, J = 7.5 Hz, 1H), 8.03–7.93 (m, 3H)

7.45 (d, J = 2.9 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H), 7.19 (d, J =

NMR (175 MHz, CDCl3): δ = 157.3, 138.1, 136.7,

2.4 Hz, 1H), 6.95 (dd, J = 8.9, 2.4 Hz, 1H), 3.91 (s, 3H) ppm.

227

ppm.

oC

(DSC, 10

13C

oC/min,

peak).

1H

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

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,

for C7H4NO3S 181.9917; Found 181.9912.

3134, 2154, 1622, 1568 cm‒1.

Procedure for the thiocyanation of indoles: Indoles (0.15

5-Nitro-3-thiocyanato-1H-indole (1f):3c Eluent petroleum

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 reaction

126–128 oC. 1H NMR (400 MHz, DMSO-d6): δ = 12.63 (s, 1H),

was completed (monitored by TLC), the reaction mixture was

8.53 (d, J = 2.2 Hz, 1H), 8.28 (s, 1H), 8.14 (dd, J = 9.2, 2.2 Hz,

purified by column chromatography on silica gel with

1H), 7.72 (d, J = 9.2 Hz, 1H) ppm.

petroleum ether/ethyl acetate to afford the pure desired

DMSO-d6): δ = 142.6, 140.0, 137.6, 127.4, 118.6, 114.9, 114.2,

products (1a-1k).

112.4, 93.7 ppm. IR (KBr) ν = 3354, 3111, 2162, 1581, 1523

3-Thiocyanato-1H-indole

(1a):3h

Eluent petroleum ether/ethyl

13C

NMR (100 MHz,

cm‒1.

acetate (2:1, V/V). pale yellow solid (26 mg, 98%), mp 72‒74

4-Methyl-3-thiocyanato-1H-indole (1g):6 Eluent petroleum

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),


NMR (100 MHz, CDCl3): δ =

7.47 (d, J = 2.9 Hz, 1H), 7.25 (d, J = 8.3 Hz, 1H), 7.17 (t, J =

oC. 1H

7.33–7.31 (m, 2H) ppm.

13C

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

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, Eluent petroleum

123.4, 113.4, 110.1, 91.9, 19.1 ppm. IR (KBr) ν = 3319, 2154,


1583, 1502, 1433 cm‒1.

86–88 oC. 1H NMR (400 MHz, CDCl3): δ = 7.75 (s, 1H), 7.49

4-Bromo-3-thiocyanato-1H-indole (1h): Eluent petroleum

(d, J = 7.9 Hz, 1H), 7.24 (m, 2H), 7.18–7.13 (m, 1H), 2.33 (s,


NMR (100 MHz, CDCl3): δ = 141.2, 132.9,

144–146 oC. 1H NMR (400 MHz, DMSO-d6): δ = 12.33 (s, 1H),

127.5, 123.6, 120.5, 119.9, 118.9, 110.7, 109.6, 8.3 ppm. IR

8.11 (d, J = 3.2 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.39 (d, J =

(KBr) ν = 3377, 2106, 2044, 1456 cm‒1.

7.6 Hz, 1H), 7.15 (t, J = 8.0 Hz, 1H) ppm. 13C NMR (100 MHz,

5-Bromo-3-thiocyanato-1H-indole (1c):3h Eluent petroleum

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,

NMR (400 MHz, CDCl3): δ = 8.77 (s, 1H),

1504, 1402 cm‒1. HRMS (ESI) m/z: [M ‒ H]‒ calcd for

3H) ppm.

131–133

13C

oC. 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,

C9H4BrN2S 250.9284; Found 250.9284. 3-Thiocyanato-1H-pyrrolo[2,3-b]pyridine

(1i):20

Eluent

CDCl3): δ = 134.7, 132.1, 129.4, 127.1, 121.5, 115.5, 113.6,

petroleum ether/ethyl acetate (2:1, V/V), white solid (20 mg,

111.6, 92.2 ppm. IR (KBr) ν = 3340, 3109, 2148, 1718, 1691

74%), mp 197–199 oC. 1H NMR (400 MHz, DMSO-d6): δ =

cm‒1.

12.60 (s, 1H), 8.40 (d, J = 3.9 Hz, 1H), 8.14 (s, 1H), 8.12 (d, J

1-Methyl-3-thiocyanato-indole

(1d):3h

Eluent

petroleum

= 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,

84–86 oC. 1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 7.2 Hz,

117.3, 112.1, 88.9 ppm. IR (KBr) ν = 2922, 2152, 1587 cm‒1.

1H), 7.32–7.18 (m, 4H), 3.74 (s, 3H) ppm. 13C NMR (100 MHz,

3-Thiocyanatobenzo[b]thiophene (1j): Eluent petroleum ether,

CDCl3): δ = 137.2, 135.1, 128.5, 123.5, 121.7, 119.0, 111.9,

white solid (26 mg, 91%), mp 82–84 oC. 1H NMR (400 MHz,

110.2, 90.0, 33.5 ppm. IR (KBr) ν = 3120, 2150, 1610, 1514

CDCl3): δ = 8.02 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 5.6 Hz, 2H),

cm‒1.

7.59–7.55 (m, 1H), 7.52–7.48 (m, 1H) ppm.


13C

NMR (100


Page 6 of 11

MHz, CDCl3): δ = 139.6, 137.3, 134.3, 125.9, 125.8, 123.3,

Adamantyl

122.3, 112.1, 109.7 ppm. IR (KBr) ν = 2154, 1869, 1655, 1554,

7-bromo-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalen

1508

cm‒1.

Anal calcd for C9H5NS2: C, 56.52; H, 2.64; N, 7.32.

e-2-carboxylate (2c): Eluent petroleum ether/ethyl acetate (20:1, V/V), white solid (54 mg, 78%), mp 134–136 oC. 1H

Found: C, 56.48; H, 2.63; N, 7.32. petroleum

NMR (400 MHz, CDCl3): δ = 8.14 (d, J = 2.2 Hz, 1H), 7.66

ether/ethyl acetate (15:1, V/V), colorless liquid (30 mg, 73%).

(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,

N-Boc-3-thiocyanato-1H-indole 1H

(1k):

Eluent

(s, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.47-7.39 (m, 2H), 1.69 (s, 9H)

6H) ppm.

13C

NMR (100 MHz, CDCl3): δ = 188.4, 164.8,

NMR (100 MHz, CDCl3): δ = 148.4, 135.4, 131.7,

141.3, 137.6, 132.1, 130.8, 130.7, 121.5, 110.2, 85.9, 65.9, 40.9,

129.1, 126.0, 124.0, 119.1, 115.7, 110.1, 99.1, 85.4, 28.1 ppm.

35.9, 33.9, 30.9, 26.7 ppm. IR (KBr) ν = 2912, 2852, 2156,

IR (KBr) ν = 2982, 2926, 2850, 2158, 2005, 1748, 1531 cm‒1.

1728, 1693, 1589 cm‒1. HRMS (ESI) m/z: [M + H]+ calcd for

ppm.

13C

HRMS (ESI) m/z: [M +

NH4]+ calcd

for C14H18N3O2S 292.1114;

C22H23BrNO3S 460.0582; Found 460.0587.

Found 292.1115.

Methyl

Procedure for the thiocyanation of β-keto carbonyl

5-methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthal

compounds: β-Keto carbonyl compounds (0.15 mmol) and R1

ene-2-carboxylate (2d): Eluent petroleum ether/ethyl acetate

(48 mg, 0.20 mmol, 1.3 equiv) were stirred in THF (1.0 mL)

(15:1, V/V), white solid (40 mg, 92%), mp 122–124 oC. 1H

for 12 h at room temperature. After reaction was completed

NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 7.9 Hz, 1H), 7.34 (t,

(monitored by TLC), the reaction mixture was purified by

J = 8.0 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 3.87 (s, 3H), 3.78 (s,

column chromatography on silica gel with petroleum

3H), 3.24–3.18 (m, 2H), 2.89–2.81 (m, 1H), 2.55–2.47 (m, 1H)

ether/ethyl acetate to afford the pure desired product.

ppm.

Adamantyl

131.9, 131.0, 128.0, 119.7, 115.7, 110.0, 65.5, 55.8, 54.1, 33.1,

1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carbo

21.2 ppm. IR (KBr) ν = 2956, 2841, 2156, 1734, 1680, 1593

xylate (2a): Eluent petroleum ether/ethyl acetate (10:1, V/V),

cm‒1. HRMS (ESI) m/z: [M + H]+ calcd for C14H14NO4S


292.0638; Found 292.0640.

CDCl3): δ = 8.03 (d, J = 7.9 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H),

Methyl

7.37 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 3.18–3.10 (m,

1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carbo

3H), 2.60–2.53 (m, 1H), 2.15 (s, 3H), 2.05 (s, 6H), 1.62 (s, 6H)

xylate (2e): Eluent petroleum ether/ethyl acetate (15:1, V/V),

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,

CDCl3): δ = 8.06 (d, J = 7.9 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H),

34.1, 30.9, 27.1 ppm. IR (KBr) ν = 2912, 2852, 2156, 1724,

7.39 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 3.82 (s, 3H),

1688, 1599 cm‒1. HRMS (ESI) m/z: [M + NH4]+ calcd for

3.24–3.12 (m, 3H), 2.64–2.57 (m, 1H) ppm.

C22H27N2O3S 399.1737; Found 399.1745.

MHz, CDCl3): δ = 189.0, 166.9, 142.9, 135.2, 130.1, 129.0,

Adamantyl

128.6, 127.6, 110.0, 65.5, 54.2, 33.9, 26.9 ppm. IR (KBr) ν =

7-methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthal

2922, 2850, 2156, 1734, 1684 cm‒1. HRMS (ESI) m/z: [M +

ene-2-carboxylate (2b): Eluent petroleum ether/ethyl acetate

H]+ calcd for C13H12NO3S 262.0532; Found 262.0541.

(15:1, V/V), white solid (59 mg, 95%), mp 134–136 oC. 1H

Adamantyl

NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 2.6 Hz, 1H), 7.18 (d,

1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate

J = 8.5 Hz, 1H), 7.13 (dd, J = 8.5, 2.6 Hz, 1H), 3.84 (s, 3H),

(2f): Eluent petroleum ether/ethyl acetate (15:1, V/V), white

3.11–3.06 (m, 3H), 2.59 – 2.50 (m, 1H), 2.15 (s, 3H), 2.07 (s,

solid (42 mg, 76%), mp 99–101 oC. 1H NMR (400 MHz,

6H), 1.62 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 189.7,

CDCl3): δ = 7.87 (d, J = 7.7 Hz, 1H), 7.74–7.70 (m, 1H),

165.3, 158.9, 135.3, 131.4, 130.2, 123.5, 110.7, 109.9, 85.6,

7.53–7.47 (m, 2H), 4.05 (d, J = 18.0 Hz, 1H), 3.62 (d, J = 18.0

66.4, 55.7, 41.0, 36.0, 34.5, 31.0, 26.5 ppm. IR (KBr) ν = 2912,

Hz, 1H), 2.16 (s, 3H), 2.05 (d, J = 3.0 Hz, 6H), 1.63 (d, J = 2.8

ppm.

13C

2852, 2156, 1724, 1685, 1610

cm‒1.


H]+ calcd for C23H26NO4S 412.1583; Found 412.1582.

13C

NMR (100 MHz, CDCl3): δ = 189.3, 166.8, 156.8,

13C

NMR (100

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,


Page 7 of 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


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

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,

C21H25N2O3S 385.1586; Found 385.1570.

132.3, 129.2, 129.0, 110.1, 67.5, 63.8, 23.9, 13.7 ppm. IR

Adamantyl

(KBr): ν = 2928, 2156, 1737, 1674, 1597 cm‒1.

5-chloro-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carb

Procedure for the thiocyanation of oxindoles: Oxindoles

oxylate (2g): Eluent petroleum ether/ethyl acetate (15:1, V/V),

(0.10 mmol) and R1 (31 mg, 0.13 mmol, 1.3 equiv) were

white solid (57 mg, 95%), mp 140–142

oC. 1H

NMR (400 MHz,

stirred in THF (1.0 mL) for 12 h at room temperature. After

CDCl3): δ = 7.79 (d, J = 8.2 Hz, 1H), 7.51 (s, 1H), 7.46 (d, J =

reaction was completed (monitored by TLC), the reaction

8.2 Hz, 1H), 4.02 (d, J = 18.2 Hz, 1H), 3.59 (d, J = 18.2 Hz,

mixture was purified by column chromatography on silica gel

1H), 2.16 (s, 3H), 2.04 (d, J = 3.0 Hz, 6H), 1.62 (d, J = 2.6 Hz,

with petroleum ether/ethyl acetate to afford the pure desired

6H) ppm.

13C

NMR (100 MHz, CDCl3): δ = 193.8, 164.4,

product.

152.5, 143.6, 131.8, 129.8, 126.9, 126.5, 109.7, 86.6, 64.5, 41.0,

3-Thiocyanato-3-(p-tolyl)indolin-2-one

40.2, 35.9, 31.1 ppm. IR (KBr): ν = 2914, 2852, 2156, 1739,

petroleum ether/ethyl acetate (2:1, V/V), yellow solid (14 mg,

1597, 1456

cm‒1.

]+

HRMS (ESI) m/z: [M + NH4

calcd for

(3a):

Eluent

48%), mp 98–100 oC. 1H NMR (400 MHz, CDCl3): δ = 8.70 (d,

C21H24ClN2O3S 419.1196; Found 419.1200.

J = 11.3 Hz, 1H), 7.38–7.34 (m, 1H), 7.27 (d, J = 9.2 Hz, 1H),

Adamantyl

7.23 (d, J = 8.3 Hz, 2H), 7.18–7.11 (m, 3H), 6.99 (d, J = 7.8 Hz,

6-methyl-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-car


boxamide (2h): Eluent petroleum ether/ethyl acetate (5:1, V/V),

140.2, 139.7, 139.2, 133.4, 130.7, 129.7, 129.3, 125.7, 125.2,


124.0, 111.1, 69.4, 21.1ppm. IR (KBr): ν = 3165, 2033, 1726,

CDCl3): δ = 7.62 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.39 (d, J =

1617 cm‒1. HRMS (ESI) m/z: [M + NH4]+ calcd for

7.8 Hz, 1H), 6.96 (s, 1H), 4.22 (d, J = 18.7 Hz, 1H), 3.18 (d, J

C16H16N3OS 298.1009; Found 298.1009.

= 18.7 Hz, 1H), 2.43 (s, 3H), 2.09 (s, 3H), 2.04 (d, J = 2.4 Hz,

1-Benzyl-3-phenyl-3-thiocyanatoindolin-2-one (3b): Eluent

NMR (100 MHz, CDCl3): δ = 198.4,

petroleum ether/ethyl acetate (5:1, V/V), white solid (33 mg,

162.5, 148.0, 139.2, 138.7, 133.2, 126.3, 125.6, 109.0, 58.1,

91%), mp 128–130 oC. 1H NMR (400 MHz, CDCl3): δ =

53.3, 41.2, 37.1, 36.3, 29.5, 21.2 ppm. IR (KBr): ν = 2908,

7.65–7.63 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.46–7.40 (m, 3H),

6H), 1.68 (s, 6H) ppm.

13C

2848, 2153, 1709, 1682, 1531, 1456

cm‒1.

HRMS (ESI) m/z:

7.35–7.28 (m, 6H), 7.21 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.9 Hz,

[M + NH4 calcd for C22H25N2O2S 381.1637; Found 381.1630.


Adamantyl

142.2, 134.6, 133.4, 130.8, 129.5, 129.2, 128.9, 127.9, 127.8,

5-oxo-6-thiocyanato-6,7,8,9-tetrahydro-5H-benzo[7]annulen

127.2, 127.0, 126.1, 123.8, 110.3, 109.3, 60.7, 44.6 ppm. IR

e-6-carboxylate (2i): Eluent petroleum ether/ethyl acetate

(KBr): ν = 2154, 1721, 1608, 1485 cm‒1. HRMS (ESI) m/z: [M

(15:1, V/V), colorless oil (55 mg, 96%). 1H NMR (400 MHz,

+ NH4]+ calcd for C22H20N3OS 374.1322; Found 374.1325.

CDCl3): δ = 7.56 (dd, J = 7.6, 0.8 Hz, 1H), 7.45–7.41 (m, 1H),

N-Boc-3-(4-methoxyphenyl)-2-oxo-3-thiocyanatoindoline

7.31 (t, J = 7.6 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 3.04–2.97 (m,

(3c): Eluent petroleum ether/ethyl acetate (15:1, V/V), pale

2H), 2.93–2.86 (m, 1H), 2.33–2.26 (m, 1H), 2.18–2.02 (m, 5H),

yellow solid (31 mg, 80%), mp 107–109 oC. 1H NMR (400

1.89 (m, 6H), 1.57 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3):

MHz, CDCl3): δ = 7.99 (d, J = 8.2 Hz, 1H), 7.48 (t, J = 8.4 Hz,

δ = 197.6, 164.7, 139.7, 136.7, 132.5, 130.7, 129.9, 126.6,

1H), 7.36 (d, J = 7.4 Hz, 1H), 7.30 (d, J = 7.5 Hz, 1H), 7.22 (d,

110.8, 84.9, 72.2, 40.6, 35.9, 33.9, 30.8, 26.9, 24.9 ppm. IR

J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 1.61 (s,

]+

(KBr): ν = 2912, 2852, 2154, 1737, 1682, 1597

cm‒1.

HRMS

9H) ppm.

13C

NMR (100 MHz, CDCl3): δ = 168.7, 159.4,

(ESI) m/z: [M + H]+ calcd for C23H26NO3S 396.1628; Found

147.8, 139.4, 138.4, 129.8, 127.4, 126.8, 126.7, 126.0, 124.6,

396.1635.

124.5, 124.0, 114.8, 113.3, 84.4, 67.8, 54.4, 27.0 ppm. IR

Ethyl

2-methyl-3-oxo-3-phenyl-2-thiocyanatopropanoate

(KBr): ν = 2978, 2927, 2027, 1789, 1732, 1606, 1506 cm‒1.

(2j):23

Eluent petroleum ether/ethyl acetate (10:1, V/V),

HRMS (ESI) m/z: [M + Na]+ calcd for C21H20N2NaO4S

colorless oil (34 mg, 87%). 1H NMR (400 MHz, CDCl3): δ =

419.1036; Found 419.1033.

7.87–7.85 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 8.0 Hz,

N-Boc



Page 8 of 11

-3-(4-methoxyphenyl)-5-methyl-2-oxo-3-thiocyanatoindolin

132.1, 123.9, 115.8, 112.5, 109.5, 17.2 ppm. IR (KBr): ν =

e-1-carboxylate (3d): Eluent petroleum ether/ethyl acetate (5:1,

3446, 3363, 2150, 1633 cm‒1. HRMS (ESI) m/z: [M + H]+

V/V), white solid (38 mg, 91%), mp 148–150 oC. 1H NMR

calcd for C8H9N2S 165.0481; Found 165.0478.

(400 MHz, CDCl3): δ = 7.85 (d, J = 8.0 Hz, 1H), 7.27 (d, J =

2-(tert-Butyl)-4-thiocyanatoaniline (4e): Eluent petroleum

5.6 Hz, 1H), 7.22 (d, J = 8.7 Hz,2H), 7.15 (s, 1H), 6.88 (d, J =

ether/ethyl acetate (10:1, V/V), yellowish oil (39 mg, 94%). 1H

13C


8.7 Hz, 2H), 3.79 (s, 3H), 2.38 (s, 3H), 1.60 (s, 9H) ppm.

NMR (100 MHz, CDCl3): δ = 169.8, 160.3, 148.8, 140.0, 137.0,

(dd, J = 8.2, 2.4 Hz, 1H), 6.63 (d, J = 8.2 Hz, 1H), 4.13 (s, 2H),

135.5, 131.4, 128.6, 127.6, 127.0, 125.3, 115.5, 114.3, 85.1,

1.41 (s, 9H) ppm.

69.0, 55.4, 28.0, 21.1 ppm. IR (KBr): ν = 2972, 2920, 2070,

135.1, 132.1, 132.0, 118.7, 112.7, 109.6, 34.5, 29.3 ppm. IR

1770, 1732, 1506 cm‒1. HRMS (ESI) m/z: [M + NH4]+ calcd

(KBr): ν =3508, 3394, 3242, 2152, 1587, 1556 cm‒1. HRMS

for C22H26N3O4S 428.1639; Found 428.1642.

(ESI) m/z: [M + H]+ calcd for C11H15N2S 207.0950; Found

Procedure for the thiocyanation of aniline derivatives:

207.0942.

Aniline derivatives (0.20 mmol) and R1 (53 mg, 0.22 mmol,

3,5-Dimethoxy-4-thiocyanatoaniline (4f): Eluent petroleum

1.1 equiv) were stirred in CH2Cl2 (1.0 mL) for 12 h at room


temperature. After reaction was completed (monitored by TLC),


the reaction mixture was purified by column chromatography

4.01 (s, 2H), 3.86 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ

on silica gel with petroleum ether/ethyl acetate to afford the

= 161.7, 151.5, 112.5, 91.4, 86.0, 56.2 ppm. IR (KBr): ν = 3362,

pure desired product.

2920, 2848, 2150 cm‒1. HRMS (ESI) m/z: [M + H]+ calcd for

4-Thiocyanatoaniline (4a):3c Eluent petroleum ether/ethyl

C9H11N2O2S 211.0536; Found 211.0541.

acetate (10:1, V/V), yellow solid (29 mg, 96%), mp 47–49 oC.

3,5-Dimethoxy-2-thiocyanatoaniline (4f '): Eluent petroleum



1H

13C

NMR (100 MHz, CDCl3): δ = 147.1,

NMR (100 MHz,

128–130 oC. 1H NMR (400 MHz, CDCl3): δ = 5.93 (d, 2.4 Hz,

CDCl3): δ = 148.8, 134.4, 116.0, 112.4, 109.4 ppm. IR (KBr): ν

1H, Ar-H), 5.92 (d, 2.4 Hz, 1H, Ar-H), 4.49 (s, 2H), 3.87 (s,

(d, J = 7.8 Hz, 2H), 3.98 (s, 2H) ppm.

= 3419, 3346, 2147, 1888, 1595

cm‒1.

13C


H]+ calcd for C7H7N2S 151.0324; Found 151.0324.

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):

Eluent petroleum

ν = 3412, 3323, 2953, 2924, 2142, 1614, 1585 cm‒1. HRMS


(ESI) m/z: [M + H]+ calcd for C9H11N2O2S 211.0536; Found

66–68 oC. 1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 8.8 Hz,

211.0537.

2H), 6.67 (d, J = 8.8 Hz, 2H), 2.99 (s, 6H) ppm. 13C NMR (100

4-(Thiocyanatoamino)benzonitrile (5a): Eluent petroleum

MHz, CDCl3): δ = 151.7, 134.5, 113.2, 112.7, 106.5, 40.2 ppm.


IR (KBr): ν = 2912, 2819, 2145, 1884, 1593, 1504 cm‒1.

107–109 oC. 1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.8

N,N-Dimethyl-4-thiocyanatoaniline


H]+

(4b):3h

calcd for C9H11N2S 179.0637;

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

Found 179.0635. Eluent

ppm. IR (KBr): ν = 2224, 2147, 1645, 1604, 1506 cm‒1. HRMS

petroleum ether/ethyl acetate (15:1, V/V), colorless oil (37 mg,

(ESI) m/z: [M ‒ H]‒ calcd for C8H4N3S 174.0131; Found

74%). 1H NMR (400 MHz, CDCl3): δ = 7.22 (s, 2H), 4.01 (s,

174.0155.

2,6-Diisopropyl-4-thiocyanatoaniline

(4c):21

2H), 2.90–2.84 (m, 2H), 1.27 (d, J = 6.8 Hz, 12H) ppm.

13C

4-(Thiocyanatoamino)bromobenzene (5b): Eluent petroleum

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.

64–66 oC. 1H NMR (400 MHz, CDCl3): δ = 7.46–7.43 (m, 2H),

2-Methyl-4-thiocyanatoaniline

(4d):4b

Eluent

petroleum

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

NMR (400 MHz, CDCl3): δ = 7.27 (s, 1H),

= 2153, 2065, 1630 cm‒1. HRMS (ESI) m/z: [M + H]+ calcd for

66–68

oC. 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,

C7H6N2SBr 228.9430; Found 228.9439. 4-(Thiocyanatoamino)fluorobenzene (5c):3e Eluent petroleum


Page 9 of 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60




NMR (400 MHz, CDCl3): δ = 7.09‒7.02 (m, 4H),

(dd, J = 8.4, 2.4 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 1.40 (s, 9H)

77–79

oC. 1H

5.11 (s, 1H) ppm.

13C

NMR (100 MHz, CDCl3): δ = 159.1 (d, J

ppm.

13C

NMR (100 MHz, CDCl3): δ = 156.7, 138.8, 131.7,

= 241.0 Hz), 139.5 (d, J = 2.6 Hz), 118.3 (d, J = 8.1 Hz), 116.3

131.5, 118.2, 112.7, 112.4, 34.9, 29.1 ppm. IR (KBr): ν = 3381,

(d, J = 22.9 Hz), 113.2 ppm. IR (KBr): ν = 3267, 2149, 1635,

2958, 2160, 1589, 1498 cm‒1.

1506 cm‒1.

3-Methyl-4-thiocyanatophenol

(6e):22

Eluent

petroleum

Eluent

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,

30%). 1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 8.8 Hz,

J = 2.4 Hz, 1H), 6.71 (dd, J = 6.0, 2.4 Hz, 1H), 2.47 (s, 3H)


ppm.

MHz, CDCl3): δ = 142.0, 129.6, 128.5, 117.8, 112.8 ppm. IR

118.6, 114.9, 112.6, 111.9, 20.9 ppm. IR (KBr): ν = 3360, 2154,

4-(Thiocyanatoamino)chlorobenzene

(KBr): ν = 2145, 1489

(5d):3e

cm‒1.

13C

NMR (100 MHz, CDCl3): δ = 158.4, 143.3, 136.0,

1586, 1492 cm‒1. (5d'):28

4-Chloro-2-thiocyanatoaniline

Eluent

petroleum

3,5-Dimethoxy-4-thiocyanatophenol (6f): Eluent petroleum

1H

ether/ethyl acetate (5:1, V/V), white solid (38 mg, 89%), mp:

NMR (400 MHz, CDCl3): δ = 7.47 (s, 1H), 7.24 (d, J = 8.8 Hz,



3.85 (s, 6H) ppm.

MHz, CDCl3): δ = 146.7, 134.8, 133.0, 123.3, 117.3, 109.3,

160.8, 112.4, 92.8, 89.1, 56.3 ppm. IR (KBr): ν = 3371, 2920,

ether/ethyl acetate (5:1, V/V), colorless oil (13 mg, 36%),

105.7 ppm. IR (KBr): ν = 2152, 1611, 1537, 1473

cm‒1.

13C

NMR (100 MHz, CDCl3): δ = 161.5,

2848, 2145, 1587, 1489 cm‒1. HRMS (ESI) m/z: [M + H]+

Procedure for the thiocyanation of phenols: phenols (0.20

calcd C9H10NO3S 212.0376; Found 212.0372.

mmol) and R1 (48 mg, 0.20 mmol, 1.0 equiv) were stirred in

1-Methoxy-2-methyl-4-thiocyanatobenzene

CH2Cl2 (1.0 mL) for 12 h at room temperature. After reaction


was completed (monitored by TLC), the reaction mixture was

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,

petroleum ether/ethyl acetate to afford the pure desired product.

3H) ppm.

4-Thiocyanatophenol

(6a):22

Eluent petroleum ether/ethyl

acetate (5:1, V/V), yellowish oil (27 mg,

89%). 1H

NMR (400

13C

(6g):26

Eluent

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.

MHz, CDCl3): δ = 7.45 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz,

Procedure for the thiocyanation of aromatic ketones:

NMR (100 MHz, CDCl3): δ = 157.9, 134.2, 117.5,

Aromatic ketones (0.20 mmol). Me3SiCl (0.20 mmol, 1.0

2H).

13C

113.6, 112.0. IR (KBr): ν = 3368, 2158, 1598, 1583 cm‒1.

equiv) and R1 (63 mg, 0.26 mmol, 1.3 equiv) were stirred in

2,6-Dimethyl-4-thiocyanatophenol (6b):22 Eluent petroleum

MeCN (1.0 mL) for 6 h at 80 oC. Then the reaction mixture was

ether/ethyl acetate (5:1, V/V), white solid (26 mg, 73%), mp:


NMR (400 MHz, CDCl3): δ = 7.20 (s, 2H), 5.05

petroleum ether/ethyl acetate to afford the pure desired product.

97–99

oC, 1H

(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. (6c):22

Eluent

petroleum

ether/ethyl acetate (5:1, V/V), white solid (23 mg, 70%), mp 59–61

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


156.1, 135.0, 131.5, 126.8, 116.6, 113.0, 112.1, 15.7. IR (KBr): ν = 3362, 2154, 1585, 1494

(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,

2-Methyl-4-thiocyanatophenol oC. 1H

1-Phenyl-2-thiocyanatopropan-1-one

cm‒1.

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 oC. 1H NMR (400 MHz, CDCl3): δ = 7.91

2-(tert-Butyl)-4-thiocyanatophenol (6d):27 Eluent petroleum

(d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 4.71 (s, 2H), 3.90

1H

(s, 3H). 13C NMR (100 MHz, CDCl3): δ = 189.1, 164.8, 130.9,

ether/ethyl acetate (5:1, V/V), colorless oil (30 mg, 72%).



Page 10 of 11

126.9, 114.4, 112.1, 55.7, 42.9. IR (KBr): ν = 2158, 1645, 1506,

109.4, 47.9, 35.7 ppm. IR (KBr): ν = 2951, 2156, 1732, 1597,

cm‒1.

1456 cm‒1. HRMS (ESI) m/z: [M + NH4]+ calcd for

2-Thiocyanato-2,3-dihydro-1H-inden-1-one (7c):23 Eluent

C10H10BrN2OS 284.9692; Found 284.9679.

petroleum ether/ethyl acetate (5:1, V/V), yellowish solid (28

Gram-Scale reaction: 5-Bromo-1H-indole (1.0 g, 5.1 mmol)

mg, 74%), mp 84–86

oC. 1H

NMR (400 MHz, CDCl3): δ = 7.83

and R1 (1.6 g, 6.6 mmol, 1.3 equiv) were stirred in THF (30 mL)

(d, J = 8.0 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.52–7.45 (m, 2H),

for 30 min at room temperature. Upon completion, the solvent

4.13 (dd, J = 8, 4.4 Hz, 1H), 3.83 (dd, J = 17.6, 8 Hz, 1H), 3.36

was evaporated in vacuum. After addition of CH2Cl2 (8.0 mL)


to the residue followed by sonic oscillation and filtration,

198.0, 151.0, 136.4, 134.1, 128.6, 126.4, 125.0, 109.9, 48.2,

flushed by CH2Cl2 (2.0 mL), pure white Saccharin (1.03 g,

34.8. IR (KBr): ν = 2154, 1635, 1463, 1431 cm‒1.

85%) was recovered. Then, the filtrate was concentrated under

5-Chloro-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7d):24

reduced pressure and purified by column chromatography on

Eluent petroleum ether/ethyl acetate (10:1, V/V), yellowish

silica gel with eluent petroleum ether/ethyl acetate to afford

(dd, J = 17.6, 4.4 Hz, 1H).

13C

solid (14 mg, 42%), mp 124–126

oC. 1H

NMR (400 MHz,

product 1c (1.17 g, 91%).

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

█

ASSOCIATED CONTENT

Supporting Information

MHz, CDCl3): δ = 196.5, 152.4, 143.3, 132.6, 129.6, 126.7,

The Supporting Information is available free of charge on the

126.2, 109.5, 48.1, 34.5. IR (KBr): ν = 2156, 1714, 1633, 1519

ACS Publications website at DOI:

cm‒1.

Copies of 1H, 13C NMR. (PDF)

6-Bromo-2-thiocyanato-2,3-dihydro-1H-inden-1-one

(7e):

█

AUTHOR INFORMATION

Eluent petroleum ether/ethyl acetate (5:1, V/V), white solid (36

Corresponding Author

mg, 67%), mp 99–101 oC. 1H NMR (400 MHz, CDCl3): δ =

*E-mail: [email protected]; [email protected]

7.96 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H),

Notes

4.13 (dd, J = 8.0, 4.4 Hz, 1H), 3.78 (dd, J = 18.0, 8.0 Hz, 1H),

The authors declare no competing financial interest.

3.31 (dd, J = 18.0, 4.4 Hz, 1H) ppm.

13C

NMR (100 MHz,

█

ACKNOWLEDGMENTS

CDCl3): δ = 196.7, 149.6, 139.3, 135.9, 128.0, 127.9, 122.9,

The financial support from the Natural Science Foundation of

109.5, 48.3, 34.5 ppm. IR (KBr): ν = 2900, 2154, 1732, 1701,

China (21572020) is acknowledged.

1595

cm‒1.


NH4]+

calcd for

█ REFERENCES

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