N-Thiocyanatosaccharin: A "sweet" Electrophilic Thiocyanation Reagent and the Synthetic Applications

Article abstract of DOI:10.1021/acs.joc.7b02850

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.

Full text of DOI:10.1021/acs.joc.7b02850

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Note
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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N-Thiocyanatosaccharin: A ‘Sweet’ Electrophilic Thiocyanation Reagent and the
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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.
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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.
hiocyano is an important functional group
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.
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,
Twidely existing in
Scheme 1 Thiocyanation reactions
+
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
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,
2014,
thiocyanation through electrolysis.7 In 2015, Samareh
and Kobra demonstrated the oxidant-free
thiocyanation by AlCl3/NH4SCN.8 In 2015, Waser
Petrosyan
reported
the
heteroarene
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oxindoles, phenols, and aromatic ketones were
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.
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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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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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
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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 =
adamantyl.
4-chloro-N-thiocyanatoaniline
(5d,
30%)
and
4-chloro-2-thiocyanatoaniline (5d', 36%) was
produced.
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.
a Reaction conditions: aniline (0.20 mmol), R1 (53 mg, 0.22 mmol, 1.1
equiv), CH2Cl2 (1.5 mL), rt, 12 h.
To widen the substrate scope of this new
thiocyanato reagent, the electrophilic thiocyanations
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.
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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).
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Scheme 3 Synthesis of 1c on gram scale.
a Reaction conditions: phenols (0.20 mmol), R1 (48 mg, 0.20 mmol, 1.0
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.
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.
█ 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
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%).
1
common solvents open to air. 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 the MS of
samples were analyzed on an Agilent (Q-TOF 6520) with an
ESI source. All IR spectra were measured on a Shimadzu
IRAffinnity-1s spectrometer. Melting points were measured on
Table 6 Thiocyanation reaction of aromatic ketonesa
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
CH2Cl2 (25.0 mL) for 30 min at room temperature. Then the
reaction mixture was filtered and the filtrate was concentrated
a Reaction conditions: ketones (0.20 mmol), R1 (63 mg, 0.26 mmol, 1.3
b
equiv), Me3SiCl (0.20 mmol, 1.0 equiv), MeCN (1.0 mL), 80 oC, 6 h.
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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
227 oC (DSC, 10 oC/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.
ether/ethyl acetate (5:1, V/V), white solid (30 mg, 98%), mp
o
1
119–121 C. H 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.
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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 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).
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 oC. 1H 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, 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.
3-Thiocyanato-1H-indole (1a):3h Eluent petroleum ether/ethyl
acetate (2:1, V/V). pale yellow solid (26 mg, 98%), mp 72‒74
4-Methyl-3-thiocyanato-1H-indole (1g):6 Eluent petroleum
1
oC. H NMR (400 MHz, CDCl3): δ = 8.69 (s, 1H), 7.82–7.80
ether/ethyl acetate (5:1, V/V), white solid (27 mg, 99%), mp
o
1
(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.
107–109 C. 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.
3-Methyl-2-thiocyanato-1H-indole (1b):19 Eluent petroleum
ether/ethyl acetate (20:1, V/V), white solid (28 mg, 98%), mp
o
1
86–88 C. H 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.
4-Bromo-3-thiocyanato-1H-indole (1h): Eluent petroleum
ether/ethyl acetate (2:1, V/V), white solid (36 mg, 95%), mp
144–146 oC. 1H 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.
5-Bromo-3-thiocyanato-1H-indole (1c):3h Eluent petroleum
ether/ethyl acetate (2:1, V/V), white solid (36 mg, 95%), mp
o
1
131–133 C. 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.
3-Thiocyanato-1H-pyrrolo[2,3-b]pyridine (1i):20 Eluent
petroleum ether/ethyl acetate (2:1, V/V), white solid (20 mg,
o
1
74%), mp 197–199 C. H 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,
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1-Methyl-3-thiocyanato-indole (1d):3h Eluent petroleum
ether/ethyl acetate (20:1, V/V), white solid (28 mg, 99%), mp
84–86 oC. 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.
o
1
white solid (26 mg, 91%), mp 82–84 C. H 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
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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,
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.
7-bromo-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalen
e-2-carboxylate (2c): Eluent petroleum ether/ethyl acetate
o
1
(20:1, V/V), white solid (54 mg, 78%), mp 134–136 C. H
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,
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.
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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
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 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
5-methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthal
ene-2-carboxylate (2d): Eluent petroleum ether/ethyl acetate
o
1
(15:1, V/V), white solid (40 mg, 92%), mp 122–124 C. H
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.
1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carbo
xylate (2a): Eluent petroleum ether/ethyl acetate (10:1, V/V),
white solid (50 mg, 88%), mp 99–101 oC. 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.
Methyl
1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene-2-carbo
xylate (2e): Eluent petroleum ether/ethyl acetate (15:1, V/V),
white solid (33 mg, 85%), mp 137–139 oC. 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
Adamantyl
7-methoxy-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthal
ene-2-carboxylate (2b): Eluent petroleum ether/ethyl acetate
o
1
(15:1, V/V), white solid (59 mg, 95%), mp 134–136 C. H
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.
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 oC. 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,
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40.5, 35.8, 31.0 ppm. IR (KBr): ν = 2912, 2850, 2156, 1732,
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.
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-carb
oxylate (2g): Eluent petroleum ether/ethyl acetate (15:1, V/V),
white solid (57 mg, 95%), mp 140–142 oC. 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. 13C 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.
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
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.
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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 oC. 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, 21.1ppm. IR (KBr): ν = 3165, 2033, 1726,
Adamantyl
6-methyl-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-car
boxamide (2h): Eluent petroleum ether/ethyl acetate (5:1, V/V),
white solid (55 mg, 97%), mp 132–134 oC. 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
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 oC. 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 oC. 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.
5-oxo-6-thiocyanato-6,7,8,9-tetrahydro-5H-benzo[7]annulen
e-6-carboxylate (2i): Eluent petroleum ether/ethyl acetate
1
(15:1, V/V), colorless oil (55 mg, 96%). H 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.
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Ethyl
2-methyl-3-oxo-3-phenyl-2-thiocyanatopropanoate
(2j):23 Eluent petroleum ether/ethyl acetate (10:1, V/V),
1
colorless oil (34 mg, 87%). H 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,
N-Boc
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132.1, 123.9, 115.8, 112.5, 109.5, 17.2 ppm. IR (KBr): ν =
-3-(4-methoxyphenyl)-5-methyl-2-oxo-3-thiocyanatoindolin
e-1-carboxylate (3d): Eluent petroleum ether/ethyl acetate (5:1,
3446, 3363, 2150, 1633 cm‒1. HRMS (ESI) m/z: [M + H]+
1
V/V), white solid (38 mg, 91%), mp 148–150 oC. H NMR
calcd for C8H9N2S 165.0481; Found 165.0478.
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(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.
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.
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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 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.
3,5-Dimethoxy-4-thiocyanatoaniline (4f): Eluent petroleum
ether/ethyl acetate (5:1, V/V), white solid (27 mg, 54%), mp
o
1
170–172 C. 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.
4-Thiocyanatoaniline (4a):3c Eluent petroleum ether/ethyl
o
acetate (10:1, V/V), yellow solid (29 mg, 96%), mp 47–49 C.
3,5-Dimethoxy-2-thiocyanatoaniline (4f '): Eluent petroleum
ether/ethyl acetate (5:1, V/V), white solid (13 mg, 32%), mp
128–130 oC. 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.
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 oC. 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, 2145, 1884, 1593, 1504 cm‒1.
HRMS (ESI) m/z: [M + H]+ calcd for C9H11N2S 179.0637;
Found 179.0635.
4-(Thiocyanatoamino)benzonitrile (5a): Eluent petroleum
ether/ethyl acetate (2:1, V/V), white solid (26 mg, 74%), mp
1
107–109 oC. 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.
2,6-Diisopropyl-4-thiocyanatoaniline
(4c):21
Eluent
petroleum ether/ethyl acetate (15:1, V/V), colorless oil (37 mg,
1
74%). H 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 oC. 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,
4-(Thiocyanatoamino)bromobenzene (5b): Eluent petroleum
ether/ethyl acetate (10:1, V/V), white solid (35 mg, 76%), mp
64–66 oC. 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
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ether/ethyl acetate (2:1, V/V), white solid (17 mg, 51%), mp
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.
77–79 oC. 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.
3-Methyl-4-thiocyanatophenol (6e):22 Eluent petroleum
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4-(Thiocyanatoamino)chlorobenzene
(5d):3e
Eluent
ether/ethyl acetate (5:1, V/V), yellowish oil (29 mg, 88%), H
petroleum ether/ethyl acetate (5:1, V/V), colorless oil (12 mg,
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.
1
30%). H 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
3,5-Dimethoxy-4-thiocyanatophenol (6f): Eluent petroleum
ether/ethyl acetate (5:1, V/V), white solid (38 mg, 89%), mp:
1
ether/ethyl acetate (5:1, V/V), colorless oil (13 mg, 36%), H
o
1
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.
158–156 C. H 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.
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 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:
1-Methoxy-2-methyl-4-thiocyanatobenzene (6g):26 Eluent
petroleum ether/ethyl acetate (15:1, V/V), colorless oil (30 mg,
1
84%). H 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 oC. Then the reaction mixture was
purified by column chromatography on silica gel with
petroleum ether/ethyl acetate to afford the pure desired product.
o
1
97–99 C, H 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.
1-Phenyl-2-thiocyanatopropan-1-one
(7a):23
Eluent
petroleum ether/ethyl acetate (10:1, V/V), yellowish oil (25 mg,
1
66%). H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.6 Hz,
2-Methyl-4-thiocyanatophenol (6c):22 Eluent petroleum
ether/ethyl acetate (5:1, V/V), white solid (23 mg, 70%), mp
59–61 oC. 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.
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
(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,
2-(tert-Butyl)-4-thiocyanatophenol (6d):27 Eluent petroleum
1
ether/ethyl acetate (5:1, V/V), colorless oil (30 mg, 72%). H
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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,
1456 cm‒1. HRMS (ESI) m/z: [M NH4]+ calcd for
C10H10BrN2OS 284.9692; Found 284.9679.
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 oC. 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 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.
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 vacuum. After addition of CH2Cl2 (8.0 mL)
to the residue followed by sonic oscillation and filtration,
flushed by CH2Cl2 (2.0 mL), 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 eluent petroleum ether/ethyl acetate to afford
product 1c (1.17 g, 91%).
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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 oC. 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.
█ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
Copies of 1H, 13C NMR. (PDF)
6-Bromo-2-thiocyanato-2,3-dihydro-1H-inden-1-one (7e):
Eluent petroleum ether/ethyl acetate (5:1, V/V), white solid (36
█ AUTHOR INFORMATION
Corresponding Author
o
1
mg, 67%), mp 99–101 C. H 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,
*E-mail: fuxue.chen@bit.edu.cn; hqyin77@bit.edu.cn
Notes
The authors declare no competing financial interest.
█ ACKNOWLEDGMENTS
The financial support from the Natural Science Foundation of
China (21572020) is acknowledged.
1595 cm‒1. HRMS (ESI) m/z: [M
+
NH4]+ calcd for
█ REFERENCES
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Eluent petroleum ether/ethyl acetate (5:1, V/V), white solid (27
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7.71-7.69 (m, 2H), 7.62 (d, J = 8.0 Hz, 1H), 4.11 (dd, J = 8.0,
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4.4 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.8,
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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,
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