Key words acrylamides - difunctionalization of alkenes - photocatalysis - chlorosulfonylation
- α-chlorosulfones
Sulfonyl group-containing compounds constitute an important class of therapeutic agents
in medicinal chemistry since this group can not only form hydrogen bonding interactions
with biological targets but also fits specific conformations that can interact with
active sites. Some studies suggest that the sulfonyl group is a key functional group
for the ligands binding at human receptors, which could be involved in central neural
system pathologies.[1 ] Additionally, the sulfonyl derivatives have been used in the development of anti-Alzheimer[2 ] and anti-HIV agents.[3 ] In the last years, a large number of sulfonamides have been reported as pharmaceuticals
and some studies suggest that they present potential application in the treatment
of diabetes and its complications,[4 ] and bacterial infections.[5 ]
The thiolation followed by oxidation of a sulfide or sulfoxide with strong oxidant
is the traditional method to access sulfone derivatives.[6 ] Other methods[7 ] include Friedel–Crafts type sulfonylation of arenes,[8 ] alkylation of sulfinate salts,[9 ] and addition reactions to alkenes and alkynes.[10 ]
Recently, the difunctionalization of alkenes has emerged as a powerful strategy for
the formation of C(sp3 )-sulfonylated compounds via radical processes.[11 ] In the last years, a few photoredox chlorosulfonylation of alkenes have been reported
using sulfonyl chloride as the sulfonyl radical source.[12 ] Visible-light induced chemoselective process provided access α-chloro and vinyl
sulfone derivatives (Scheme [1a ]).[13 ] A similar difunctionalization has been applied to α-CF3 styrenes using Ir(ppy)3 as photocatalyst (Scheme [1b ]).[14 ] Reiser[15 ] and Hu’s[16 ] groups reported a visible-light-mediated photocatalyzed protocol for styrene derivatives,
unactivated olefins, and alkynes using Cu photocatalysts (Scheme [1c ]). Here we report a visible-light-mediated regioselective chlorosulfonylation of
acrylamides to access amides with a quaternary center in α-position (Scheme [1d ]).
We initiated our studies by monitoring the reaction of acrylamide 1 and tosyl chloride (2a ) under various photocatalytic conditions. With 1 mol% of iridium catalyst such as
[Ir(dF(CF3 )ppy)2 (dtbpy)]PF6 (E
Ir(IV)/Ir(III)* = –0.89 V vs SCE), [Ir(dtbbpy)(ppy)2 ]PF6 (E
Ir(IV)/Ir(III)* = –0.96 V vs SCE) or fac -Ir(ppy)3 (E
Ir(IV)/Ir(III)* = –1.73 V vs SCE) in a 9:1 mixture of acetonitrile and water under irradiation with
2 Kessil LED lights the yield of the desired product was found to be very low (Table
[1 ], entries 1–3). Instead with light emitting diodes (7.2 W m–1 ) the product yield was increased up to 44% (entry 4). When the amount of water is
increased until a 5:1 mixture (MeCN/H2 O), the yield dropped to 19% (entry 5) while a decrease (20:1, MeCN/H2 O) leads to better yield (entry 6). The optimal conditions were found for 5 equivalents
of water with 82% yield of 3a . The use of LED strip or Kessil LED light led to similar yields (entries 7, 8). When
the reaction was carried out in the absence of water, the yield drops to 57% showing
its beneficial effect in the reaction (entry 9).
Scheme 1 Chlorosulfonylation of alkenes
Table 1 Optimization of the Reaction Conditionsa
Entry
Photocatalyst
Solvent
Light
Time (h)
Yield (%)b
1
[Ir(dF(CF3 )ppy)2 (dtbpy)]PF6
MeCN:H2 O (9:1)
2 Kessil LED (40 W)
16
16
2
[Ir(dtbbpy)(ppy)2 ]PF6
MeCN:H2 O (9:1)
2 Kessil LED (40 W)
16
6
3
fac -Ir(ppy)3
MeCN:H2 O (9:1)
2 Kessil LED (40 W)
16
18
4
fac -Ir(ppy)3
MeCN:H2 O (9:1)
LED strip (33 W)
22
44c
5
fac -Ir(ppy)3
MeCN:H2 O (5:1)
LED strip (33 W)
22
19
6
fac -Ir(ppy)3
MeCN:H2 O (20:1)
LED strip (33 W)
22
54c
7
fac -Ir(ppy)3
MeCNd
LED strip (33 W)
22
82c
8
fac -Ir(ppy)3
MeCNd
1 Kessil LED (40 W)
22
81
9
fac -Ir(ppy)3
MeCN
1 Kessil LED (40 W)
22
57
a Reaction conditions: Acrylamide 1 (1.0 equiv), tosyl chloride (2a ; 2.5 equiv), photocatalyst (1 mol%), solvent (0.1 M), LED (455 nm) at rt.
b Yield determined by 1 H NMR analysis using 1,3,5-trimethoxybenzene as internal standard.
c Isolated yield.
d Five equiv of H2 O were added.
After optimizing the reaction conditions, we evaluated the substrate scope and generality
of the developed method with a variety of acrylamides and sulfonyl chlorides. First,
we investigated the scope of acrylamides with p -toluenesulfonyl chloride (Scheme [2 ]). A number of acrylamides with different substitution on the benzene ring on ortho -, meta - or para - position containing electron-withdrawing groups (Br, CF3 ) and electron-donating groups (Me, OMe, OEt) were used to afford chlorosulfonylation
products 3b –i in moderate to good yields showing functional group tolerance. The reaction between
disubstituted arylacrylamides 1j and 1k and tosyl chloride afforded the desired products 3j and 3k in quantitative and 56% yield, respectively. N -(Thiazol-2-yl)methacrylamide was found to be compatible with the reaction conditions
allowing the isolation of 3l in 54% yield. The reaction with the N -phenylacrylamide furnished 3m , which contains no tertiary center in 52% yield. The limitation was found for N -(4-nitrophenyl)methacrylamide, which did not yield to product 3n . To demonstrate the scalability of the reaction, one gram scale experiment with 1a was run and 3a was isolated in 58% yield.
Next, we examined the scope of sulfonyl chlorides under the optimal conditions (Scheme
[3 ]). We observed that both electron-rich and electron-poor sulfonyl chlorides 2o –p underwent the coupling with 1a in good yields. The reaction with p -nitro derivative afforded 3q in 55% yield while m -nitro derivative showed lower reactivity giving 21% yield of 3r . The reaction with disubstituted sulfonyl chloride also afforded the desired product
3s in 57% yield. Heterocyclic sulfonyl chlorides were tolerated and the thiophene derivative
3t can be isolated in 69% yield. Aliphatic sulfonyl chlorides were also suitable substrates
for this transformation. 1-Butane- and 2-propanesulfonyl chloride afforded 3u and 3v in 56 and 64% yield, respectively. Remarkably, product 3w synthesized from cyclopropanesulfonyl chloride was isolated in 90% yield.
Scheme 2 Substrate scope for acrylamides. Reagents and conditions : 1 (1.0 equiv), 2a (2.0 equiv), fac -Ir(ppy)3 (1 mol%), MeCN (0.1 M), H2 O (5 equiv) under argon and irradiation with a Kessil LED (40 W) at rt for 22 h. Isolated
yields are shown. NR: No reaction. a 2.5 equiv of 2a were used. b One gram-scale experiment.
Control experiments proved that both light and catalyst are necessary in the chlorosulfonylation
reaction (Scheme [4 ]). In the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), starting material
was exclusively observed, which points towards a radical mechanism.
Scheme 3 Substrate scope for sulfonyl chlorides. Reagents and conditions : 1 (1.0 equiv), 2a (2.0 equiv), fac -Ir(ppy)3 (1 mol%), MeCN (0.1 M), H2 O (5 equiv) under argon and irradiation with a Kessil LED (40 W) at rt for 22 h. Isolated
yields are shown. a 2.5 equiv of 2 were used.
The mechanistic proposal is illustrated in Scheme [5 ]. The catalytic cycle begins with the visible-light irradiation of photocatalyst.
Then, the sulfonyl radical is generated by S–Cl bond cleavage via reductive SET.[6 ] Subsequent addition of the sulfonyl radical to the double bond of the acrylamide
affords a tertiary radical, which undergoes a SET process with the oxidized catalyst
to regenerate it. Finally, the carbocation is trapped with the halide leading to the
α-chlorosulfonyl acrylamide.
In conclusion, we have developed the synthesis of quaternary substituted acyclic α-chlorosulfonyl
amides by photoredox chlorosulfonylation of N -arylacrylamides. The products are obtained in moderate to good yields and the transformation
is amenable to a broad range of substrates.
Scheme 4 Control experiments
Scheme 5 Mechanistic proposal
All manipulations of air and moisture sensitive species were performed under argon
atmosphere, unless otherwise stated. Glassware were dried with a heat gun under vacuum.
NEt3 was dried over CaH2 , distilled under vacuum and stored over molecular sieves (3 Å) under inert atmosphere.
Anhydrous solvents, where necessary, were dried by a MBRAUN MB-SPS-800 apparatus.
Starting materials sourced from commercial suppliers were used as received, unless
otherwise stated. Reactions were monitored using analytical TLC plates (Scharlab;
silica gel 60 F254, 0.20 mm) visualized by UV-light at 254 nm. Silica gel grade 60
(230–400 mesh, Silicycle Inc.) was used for column chromatography. 1 H, 13 C and 19 F NMR spectra were recorded on either Mercury VX-300, Bruker 400, or Unity 500 MHz
Varian spectrometers at rt. Chemical shifts are given in ppm (δ) downfield from TMS,
with calibration the residual CHCl3 signals (δH = 7.26 for 1 H NMR and δC = 77.2 for 13 C NMR). Coupling constants (J ) are in hertz (Hz) and signals are described as follows: s, singlet; d, doublet;
t, triplet; q, quartet; quint, quintet; sext, sextet; sept, septet; br s, broad singlet;
dd, double doublet; ddd, double doublet of doublets; tt, triple triplet and m, multiplet.
High-resolution analyses (HRMS) were performed on an Agilent 6210 time of-flight LC/MS.
IR spectra were recorded on an Agilent Cart 630 FTIR spectrometer.
Acrylamides 1; General Procedure[17 ]
Acrylamides 1; General Procedure[17 ]
To a round-bottomed flask were added a solution of the corresponding aniline (11.0
mmol, 1.0 equiv) in anhyd DCM (0.1 M) and NEt3 (2.0 equiv). The mixture was stirred at 0 °C and the respective acyl chloride (1.5
equiv) was added slowly under argon atmosphere. The resulting solution was stirred
at rt until no starting material was observed by TLC. The reaction mixture was quenched
with H2 O (50 mL) and extracted with DCM (3 ×). The combined organic layers were washed with
brine (3 ×), dried (anhyd Na2 SO4 ), and concentrated under vacuum. The residue was purified by flash chromatography
on silica gel using DCM and EtOAc (1:0 → 9:1, v/v) as the eluent to give the corresponding
acrylamide 1 .
N -Phenylmethacrylamide (1a)[18 ]
N -Phenylmethacrylamide (1a)[18 ]
General procedure was followed to afford 1a as a white solid; yield: 1.47 g (85%).
1 H NMR (300 MHz, CDCl3 ): δ = 7.64–7.50 (m, 2 H), 7.47 (br s, 1 H), 7.38–7.30 (m, 2 H), 7.16–7.07 (m, 1 H),
5.97–5.63 (m, 1 H), 5.47 (dd, J = 1.6, 0.7 Hz, 1 H), 2.07 (dd, J = 1.6, 0.9 Hz, 3 H).
N -(o -Tolyl)methacrylamide (1b)[19 ]
N -(o -Tolyl)methacrylamide (1b)[19 ]
General procedure was followed to afford 1b as a white solid; yield: 0.55 g (67%).
1 H NMR (300 MHz, CDCl3 ): δ = 7.93 (d, J = 8.0 Hz, 1 H), 7.36 (br s, 1 H), 7.24–7.16 (m, 2 H), 7.08 (td, J = 7.5, 1.3 Hz, 1 H), 5.84–5.75 (m, 1 H), 5.47 (dd, J = 1.6, 0.8 Hz, 1 H), 2.29 (s, 3 H), 2.09 (dd, J = 1.6, 0.9 Hz, 3 H).
N -(2-Methoxyphenyl)methacrylamide (1c)[19 ]
N -(2-Methoxyphenyl)methacrylamide (1c)[19 ]
General procedure was followed to afford 1c as a brown oil; yield: 0.53 g (69%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.43 (dd, J = 8.0, 1.8 Hz, 1 H), 8.24 (br s, 1 H), 7.06 (td, J = 7.7, 1.8 Hz, 1 H), 6.98 (td, J = 7.7, 1.6 Hz, 1 H), 6.89 (dd, J = 8.0, 1.6 Hz, 1 H), 5.84–5.83 (m, 1 H), 5.55– 5.36 (m, 1 H), 3.90 (s, 3 H), 2.08
(dd, J = 1.6, 0.9 Hz, 3 H).
N -(2-Bromophenyl)methacrylamide (1d)[20 ]
N -(2-Bromophenyl)methacrylamide (1d)[20 ]
General procedure was followed to afford 1d as a brown oil; yield: 0.14 g (20%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.45 (d, J = 8.1 Hz, 1 H), 8.15 (br s, 1 H), 7.55 (d, J = 8.1 Hz, 1 H), 7.33 (t, J = 7.8 Hz, 1 H), 6.99 (t, J = 7.8 Hz, 1 H), 5.93 (s, 1 H), 5.53 (s, 1 H), 2.11 (s, 3 H).
N -(3-Bromophenyl)methacrylamide (1e)[21 ]
N -(3-Bromophenyl)methacrylamide (1e)[21 ]
General procedure was followed to afford 1e as a white solid; yield: 0.77 g (99%).
1 H NMR (300 MHz, CDCl3 ): δ = 7.83 (t, J = 1.9 Hz, 1 H), 7.58–7.39 (m, 2 H), 7.26–7.23 (m, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 5.87–5.68 (m, 1 H), 5.51–5.48 (m, 1 H), 2.06 (dd, J = 1.6, 0.9 Hz, 3 H).
N -(4-Ethoxyphenyl)methacrylamide (1f)[22 ]
N -(4-Ethoxyphenyl)methacrylamide (1f)[22 ]
General procedure was followed to afford 1f as a pale-red solid; yield: 1.27 g (85%).
1 H NMR (400 MHz, CDCl3 ): δ = 7.45 (d, J = 9.0 Hz, 2 H), 7.37 (br s, 1 H), 6.87 (d, J = 9.0 Hz, 2 H), 5.78–5.77 (m, 1 H), 5.43 (dd, J = 1.7, 0.8 Hz, 1 H), 4.02 (q, J = 7.0 Hz, 2 H), 2.06 (dd, J = 1.6, 0.9 Hz, 2 H), 1.40 (t, J = 7.0 Hz, 3 H).
N -(4-Bromophenyl)methacrylamide (1g)[23 ]
N -(4-Bromophenyl)methacrylamide (1g)[23 ]
General procedure was followed to afford 1g as a white solid; yield: 1.26 g (91%).
1 H NMR (400 MHz, CDCl3 ): δ = 7.48–7.44 (m, 4 H), 5.79 (br s, 1 H), 5.48–5.49 (m, 1 H), 2.06 (dd, J = 1.6, 0.9 Hz, 1 H).
N -(4-(Trifluoromethyl)phenyl)methacrylamide (1h)[19 ]
N -(4-(Trifluoromethyl)phenyl)methacrylamide (1h)[19 ]
General procedure was followed to afford 1h as a white solid; yield: 0.35 g (99%).
1 H NMR (400 MHz, CDCl3 ): δ = 7.70 (d, J = 8.6 Hz, 2 H), 7.60 (d, J = 8.6 Hz, 2 H + br s, 1 H), 5.85–5.75 (m, 1 H), 5.53–5.52 (m, 1 H), 2.08 (dd, J = 1.6, 0.9 Hz, 3 H).
19 F NMR (282 MHz, CDCl3 ): δ = –62.2.
N -(p -Tolyl)methacrylamide (1i)[18 ]
N -(p -Tolyl)methacrylamide (1i)[18 ]
General procedure was followed to afford 1i as a white solid; yield: 0.74 g (90%).
1 H NMR (400 MHz, CDCl3 ): δ = 7.44 (d, J = 8.4 Hz, 2 H + br s, 1 H), 7.14 (d, J = 8.4 Hz, 2 H), 5.85–5.70 (m, 1 H), 5.44 (dd, J = 1.7, 0.8 Hz, 1 H), 2.32 (s, 3 H), 2.06 (dd, J = 1.6, 0.9 Hz, 3 H).
N -(3,5-Dimethylphenyl)methacrylamide (1j)[24 ]
N -(3,5-Dimethylphenyl)methacrylamide (1j)[24 ]
General procedure was followed to afford 1j as a white solid; yield: 0.81 g (99%).
1 H NMR (300 MHz, CDCl3 ): δ = 7.39 (br s, 1 H), 7.20 (s, 2 H), 6.77 (s, 1 H), 5.85–5.64 (m, 1 H), 5.44 (d,
J = 2.1 Hz, 1 H), 2.30 (s, 6 H), 2.06 (dd, J = 1.5, 0.9 Hz, 3 H).
N -(4-Cyano-3-(trifluoromethyl)phenyl)methacrylamide (1k)[25 ]
N -(4-Cyano-3-(trifluoromethyl)phenyl)methacrylamide (1k)[25 ]
To a solution of methacrylamide (4.5 mmol, 1.7 equiv) in anhyd DMF (0.1 M) was added
4-cyano-3-trifluoromethylphenyl fluoride (1.0 equiv) at rt. The solution was cooled
in a NaCl/ice (1/3) bath to –20 °C. To this cooled solution was added NaH (2.5 equiv),
portionwise, while keeping the reaction temperature below 70 °C. The reaction mixture
was allowed to cool to rt and stirred for 4 h under an argon atmosphere. H2 O was added followed by aq 18% HCl (7.0 equiv) and hexane. The resulted slurry was
allowed to stir overnight. The solid was filtered, washed with H2 O (3 ×) and hexane (3 ×) and concentrated under vacuum. The residue was purified by
flash chromatography on a silica gel using DCM and EtOAc (1:0 → 9:1, v/v) as the eluent
to give the titled compound 1k as a pale-yellow solid; yield: 0.46 g (69%).
N -(Thiazol-2-yl)methacrylamide (1l)[26 ]
N -(Thiazol-2-yl)methacrylamide (1l)[26 ]
General procedure was followed to afford 1l as a pale-yellow solid; yield: 0.46 g (69%).
1 H NMR (300 MHz, CDCl3 ): δ = 10.62 (br s, 1 H), 7.43 (d, J = 3.6 Hz, 1 H), 6.99 (d, J = 3.6 Hz, 1 H), 5.96 (q, J = 1.0 Hz, 1 H), 5.64 (q, J = 1.6 Hz, 1 H), 2.11 (dd, J = 1.6, 1.0 Hz, 3 H).
N -Phenylmethacrylamide (1m)[27 ]
N -Phenylmethacrylamide (1m)[27 ]
General procedure was followed to afford 1m as a brown solid; yield: 1.13 g (71%).
1 H NMR (400 MHz, CDCl3 ): δ = 7.58 (d, J = 8.0 Hz, 2 H), 7.37–7.31 (m, 2 H), 7.13 (t, J = 7.4 Hz, 1 H), 6.44 (dd, J = 16.9, 1.3 Hz, 1 H), 6.25 (dd, J = 16.9, 10.2 Hz, 1 H), 5.78 (dd, J = 10.2, 1.3 Hz, 1 H).
N -(4-Nitrophenyl)methacrylamide (1n)[28 ]
N -(4-Nitrophenyl)methacrylamide (1n)[28 ]
General procedure was followed to afford 1n as a pale-yellow solid; yield: 0.94 g (63%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.24 (d, J = 9.2 Hz, 2 H), 7.76 (d, J = 9.2 Hz, 2 H), 7.74 (br s, 1 H), 5.85 (d, J = 0.9 Hz, 1 H), 5.58 (d, J = 1.6 Hz, 1 H), 2.09 (dd, J = 1.6, 0.9 Hz, 2 H).
Chlorosulfonylation of Acrylamides 1; General Procedure
Chlorosulfonylation of Acrylamides 1; General Procedure
To an oven-dried Schlenk tube (10 mL size) equipped with a stirring bar were added
the acrylamide 1 (0.1 mmol, 1.0 equiv), sulfonyl chloride 2 (0.2–0.25 mmol, 2.0–2.5 equiv) and fac -Ir(ppy)3 (1.0 mol%). Then, a mixture of anhyd MeCN/distilled H2 O (1 mL, 0.5 mmol, 5 equiv), previously degasified over 15 min by positive flow of
argon, was added. The resulting solution was deoxygenated by three freeze-pump-thaw
cycles. The reaction mixture was irradiated with a Kessil LED (40W, λmax = 455 nm), under argon at rt. After 22 h, the mixture was filtered on Celite and
concentrated under vacuum. The residue was purified by flash chromatography on silica
gel to give the desired product 3 .
Gram-Scale Experiment
To an oven-dried Schlenk tube (100 mL size) equipped with a stirring bar were added
the acrylamide 1a (1 g, 6.2 mmol, 1.0 equiv), sulfonyl chloride 2a (15.5 mmol, 2.5 equiv) and fac -Ir(ppy)3 (1.0 mol%). Then, a mixture of anhyd MeCN/distilled H2 O (60 mL, 31.0 mmol, 5 equiv), previously degasified over 15 min by positive flow
of argon, was added. The resulting solution was deoxygenated by three freeze-pump-thaw
cycles. The reaction mixture was irradiated with a Kessil LED (40W, λmax = 455 nm), under argon at rt. After 22 h, the reaction mixture was filtered on Celite
and concentrated under vacuum. The residue was purified by flash chromatography on
a silica gel to give 3a as a white solid; yield: 1.26 g (58%).
2-Chloro-2-methyl-N -phenyl-3-tosylpropanamide (3a)
2-Chloro-2-methyl-N -phenyl-3-tosylpropanamide (3a)
White solid; mp 51–53 °C; yield: 27.1 mg (81%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.54 (br s, 1 H), 7.80 (d, J = 8.3 Hz, 2 H), 7.50 (d, J = 7.4 Hz, 2 H), 7.36 (t, J = 7.9 Hz, 2 H), 7.29 (d, J = 8.3 Hz, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 4.23 (d, J = 14.6 Hz, 1 H), 3.73 (d, J = 14.6 Hz, 1 H), 2.37 (s, 3 H), 1.93 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.2, 145.2, 137.5, 137.0, 130.0 (2 C), 129.2 (2 C), 128.4 (2 C), 125.5, 120.6
(2 C), 66.4, 65.5, 31.2, 21.7.
HRMS (ESI-TOF): m /z calcd for C17 H18 ClNO3 SNa [M + Na]+ : 374.0594; found: 374.0581.
IR: 3358, 2927, 1683, 1597, 1533, 1444, 1321, 1144, 1086, 756, 574 cm–1 .
2-Chloro-2-methyl-N -(o -tolyl)-3-tosylpropanamide (3b)
2-Chloro-2-methyl-N -(o -tolyl)-3-tosylpropanamide (3b)
White solid; mp 54–55 °C; yield: 20.4 mg (56%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.52 (br s, 1 H), 7.86–7.73 (m, 3 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.25–7.19 (m, 2 H), 7.12 (td, J = 7.4, 1.3 Hz, 1 H), 4.25 (d, J = 14.5 Hz, 1 H), 3.73 (d, J = 14.5 Hz, 1 H), 2.39 (s, 3 H), 2.33 (s, 3 H), 1.96 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.3, 145.2, 137.8, 135.0, 130.7, 130.0 (2 C), 129.8, 128.3 (2 C), 127.0,
126.0, 122.9, 66.9, 65.5, 31.4, 21.8, 17.7.
HRMS (ESI-TOF): m /z calcd for C18 H20 ClNO3 SNa [M + Na]+ : 388.0750; found: 388.0749.
IR: 3412, 3364, 2924, 2359, 2341, 1685, 1521, 1457, 1321, 1146, 1086, 755, 669, 574
cm–1 .
2-Chloro-N -(2-methoxyphenyl)-2-methyl-3-tosylpropanamide (3c)
2-Chloro-N -(2-methoxyphenyl)-2-methyl-3-tosylpropanamide (3c)
Pale yellow solid; mp 97–100 °C; yield: 20.4 mg (53%).
1 H NMR (400 MHz, CDCl3 ): δ = 9.21 (br s, 1 H), 8.20 (dd, J = 8.0, 1.6 Hz, 1 H), 7.80 (d, J = 8.3 Hz, 2 H), 7.25 (d, J = 7.2 Hz, 2 H), 7.09 (td, J = 7.8, 1.6 Hz, 1 H), 6.95 (td, J = 7.8, 1.4 Hz, 1 H), 6.90 (dd, J = 8.1, 1.4 Hz, 1 H), 4.20 (d, J = 14.6 Hz, 1 H), 3.92 (s, 3 H), 3.76 (d, J = 14.6 Hz, 1 H), 2.33 (s, 3 H), 1.95 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 166.6, 148.6, 145.1, 137.3, 129.8 (2 C), 128.5 (2 C), 126.9, 124.8, 121.1,
119.6, 110.2, 66.4, 65.3, 56.1, 31.0, 21.7.
HRMS (ESI-TOF): m /z calcd for C18 H20 ClNO4 SNa [M + Na]+ : 404.0699; found: 404.0699.
IR: 3394, 2920, 1681, 1599, 1530, 1487, 1463, 1290, 1142, 1116, 1027, 887, 751, 574
cm–1 .
N -(2-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3d)
N -(2-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3d)
Colorless oil; yield: 26.0 mg (60%).
1 H NMR (300 MHz, CDCl3 ): δ = 9.13 (br s, 1 H), 8.24 (dd, J = 8.2, 1.6 Hz, 1 H), 7.81 (d, J = 8.3 Hz, 2 H), 7.57 (dd, J = 8.1, 1.4 Hz, 1 H), 7.38–7.30 (m, 1 H), 7.28 (d, J = 8.3 Hz, 2 H), 7.04 (ddd, J = 8.0, 7.5, 1.6 Hz, 1 H), 4.24 (d, J = 14.6 Hz, 1 H), 3.74 (d, J = 14.6 Hz, 1 H), 2.34 (s, 3 H), 1.96 (s, 3 H).
13 C NMR (75 MHz, CDCl3 ): δ = 167.2, 145.3, 137.3, 135.1, 132.5, 130.0 (2 C), 128.6 (2 C), 128.5, 126.2,
121.8, 114.5, 66.5, 65.5, 31.2, 21.7.
HRMS (ESI-TOF): m /z calcd for C17 H17 BrClNO3 SNa [M + Na]+ : 451.9699; found: 451.9705.
IR: 3356, 2924, 1692, 1595, 1530, 1439, 1323, 1146, 1086, 1025, 755 cm–1 .
N -(3-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3e)
N -(3-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3e)
White solid; mp 112–114 °C; yield: 24.0 mg (56%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.55 (br s, 1 H), 7.82–7.76 (m, 3 H), 7.39 (ddd, J = 8.1, 2.0, 1.0 Hz, 1 H), 7.33–7.28 (m, 3 H), 7.21 (t, J = 8.0 Hz, 1 H), 4.22 (d, J = 14.6 Hz, 1 H), 3.71 (d, J = 14.6 Hz, 1 H), 2.39 (s, 3 H), 1.92 (s, 3 H).
13 C NMR (75 MHz, CDCl3 ): δ = 167.3, 145.3, 138.2, 137.4, 130.4, 130.0 (2 C), 128.4, 128.3 (2 C), 123.5,
122.8, 119.1, 66.3, 65.4, 31.2, 21.8.
HRMS (ESI-TOF): m /z calcd for C17 H17 BrClNO3 SNa [M + Na]+ : 451.9699; found: 451.9705.
IR: 3354, 2928, 1687, 1590, 1526, 1477, 1321, 1144, 1086, 777, 680, 574 cm–1 .
2-Chloro-N -(4-ethoxyphenyl)-2-methyl-3-tosylpropanamide (3f)
2-Chloro-N -(4-ethoxyphenyl)-2-methyl-3-tosylpropanamide (3f)
Brown oil; yield: 28.5 mg (76%).
1 H NMR (500 MHz, CDCl3 ): δ = 8.44 (br s, 1 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 9.0 Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 6.87 (d, J = 9.0 Hz, 2 H), 4.21 (d, J = 14.6 Hz, 1 H), 4.02 (q, J = 7.0 Hz, 2 H), 3.72 (d, J = 14.6 Hz, 1 H), 2.38 (s, 3 H), 1.92 (s, 3 H), 1.40 (t, J = 7.0 Hz, 3 H).
13 C NMR (126 MHz, CDCl3 ): δ = 167.1, 156.7, 145.13, 137.6, 129.9 (2 C), 129.8, 128.3 (2 C), 122.6 (2 C),
114.9 (2 C), 66.4, 65.5, 63.8, 31.2, 21.7, 14.9.
HRMS (ESI-TOF): m /z calcd for C19 H22 ClNO4 SNa [M + Na]+ : 418.0856; found: 418.0858.
IR: 3356, 2980, 1675, 1597, 1510, 1317, 1231, 1142, 1086, 1043, 736, 572, 524 cm–1 .
N -(4-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3g)
N -(4-Bromophenyl)-2-chloro-2-methyl-3-tosylpropanamide (3g)
Yellow solid; mp 55–57 °C; yield: 29.9 mg (73%).
1 H NMR (500 MHz, CDCl3 ): δ = 8.55 (br s, 1 H), 7.79 (d, J = 8.3 Hz, 2 H), 7.47 (d, J = 8.9 Hz, 2 H), 7.42 (d, J = 8.9 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 4.21 (d, J = 14.6 Hz, 1 H), 3.71 (d, J = 14.6 Hz, 1 H), 2.39 (s, 3 H), 1.92 (s, 3 H).
13 C NMR (126 MHz, CDCl3 ): δ = 167.4, 145.3, 137.56, 136.1, 132.2 (2 C), 130.0 (2 C), 128.3 (2 C), 122.3 (2
C), 118.3, 66.4, 65.5, 31.2, 21.8.
HRMS (ESI-TOF): m /z calcd for C17 H17 BrClNO3 SNa [M + Na]+ : 451.9699; found: 451.9698.
IR: 3360, 2924, 1687, 1524, 1593, 1524, 1489, 1396, 1321, 1144, 1086, 818, 574 cm–1 .
2-Chloro-2-methyl-3-tosyl-N -[4-(trifluoromethyl)phenyl]propenamide (3h)
2-Chloro-2-methyl-3-tosyl-N -[4-(trifluoromethyl)phenyl]propenamide (3h)
White solid; mp 56–58 °C; yield: 25.7 mg (64%).
1 H NMR (500 MHz, CDCl3 ): d = 8.71 (br s, 1 H), 7.79 (d, J = 8.4 Hz, 2 H), 7.67 (d, J = 8.8 Hz, 2 H), 7.62 (d, J = 8.8 Hz, 2 H), 7.30 (d, J = 8.4 Hz, 2 H), 4.23 (d, J = 14.6 Hz, 1 H), 3.72 (d, J = 14.6 Hz, 1 H), 2.39 (s, 3 H), 1.94 (s, 3 H).
13 C NMR (126 MHz, CDCl3 ): δ = 167.6, 145.4, 137.5, 130.0 (2 C), 128.3 (2 C), 126.4 (q, 3
J
C,F = 3.8 Hz, 2 C), 120.3 (2 C), 66.4, 65.6, 31.2, 21.7.
19 F NMR (282 MHz, CDCl3 ): δ = –61.0.
HRMS (ESI-TOF): m /z calcd for C18 H17 ClF3 NO3 SNa [M + Na]+ : 442.0467; found: 442.0469.
IR: 3349, 2924, 1690, 1601, 1530, 1321, 1142, 1116, 1068, 842, 574 cm–1 .
2-Chloro-2-methyl-N -(p -tolyl)-3-tosylpropanamide (3i)
2-Chloro-2-methyl-N -(p -tolyl)-3-tosylpropanamide (3i)
White solid; mp 80–82 °C: yield: 24.9 mg (68%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.47 (s, 1 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.15 (d, J = 8.0 Hz, 2 H), 4.22 (d, J = 14.6 Hz, 1 H), 3.72 (d, J = 14.6 Hz, 1 H), 2.38 (s, 3 H), 2.33 (s, 3 H), 1.93 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.1, 145.2, 137.6, 135.2, 134.4, 130.0 (2 C), 129.7 (2 C), 128.4 (2 C), 120.7
(2 C), 66.5, 65.5, 31.2, 21.7, 21.1.
HRMS (ESI-TOF): m /z calcd for C18 H20 ClNO3 SNa [M + Na]+ : 388.0750; found: 388.0753.
IR: 3356, 2922, 2851, 1681, 1597, 1523, 1405, 1321, 1144, 1086, 814, 568, 552, 512
cm–1 .
2-Chloro-N -(3,5-dimethylphenyl)-2-methyl-3-tosylpropanamide (3j)
2-Chloro-N -(3,5-dimethylphenyl)-2-methyl-3-tosylpropanamide (3j)
Colorless oil; yield: 37.7 mg (>99%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.44 (br s, 1 H), 7.81 (d, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H), 7.13 (s, 2 H), 6.81 (s, 1 H), 4.21 (d, J = 14.6 Hz, 1 H), 3.72 (d, J = 14.6 Hz, 1 H), 2.38 (s, 3 H), 2.31 (s, 6 H), 1.93 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.0, 145.2, 138.92 (2 C), 137.6, 136.8, 130.0 (2 C), 128.4 (2 C), 127.2,
118.3 (2 C), 66.5, 65.4, 31.2, 21.7, 21.5 (2 C).
HRMS (ESI-TOF): m /z calcd for C19 H22 ClNO3 SNa [M + Na]+ : 402.0907; found: 402.0906.
IR: 3358, 2920, 1683, 1597, 1545, 1454, 1321, 1142, 1086, 842 cm–1 .
2-Chloro-N -[4-cyano-3-(trifluoromethyl)phenyl]-2-methyl-3-tosylpropanamide (3k)
2-Chloro-N -[4-cyano-3-(trifluoromethyl)phenyl]-2-methyl-3-tosylpropanamide (3k)
Yellow oil; yield: 25.0 mg (56%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.94 (br s, 1 H), 8.07 (d, J = 2.2 Hz, 1 H), 7.92 (dd, J = 8.5, 2.2 Hz, 1 H), 7.84 (d, J = 8.5 Hz, 1 H), 7.79 (d, J = 8.3 Hz, 2 H), 7.34 (d, J = 7.9 Hz, 2 H), 4.22 (d, J = 14.6 Hz, 1 H), 3.72 (d, J = 14.6 Hz, 1 H), 2.43 (s, 3 H), 1.93 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 168.3, 145.6, 141.2, 137.5, 136.0, 134.3 (q, 2
J
C,F = 32.9 Hz) 130.2 (2 C), 128.2 (2 C), 122.8, 118.2 (q, 3
J
C,F = 5.0 Hz), 115.4, 66.2, 65.7, 31.2, 21.8.
19 F NMR (376 MHz, CDCl3 ): δ = –62.1.
HRMS (ESI-TOF): m /z calcd for C19 H16 ClF3 N2 O3 SNa [M + Na]+ : 467.0420; found: 467.0427.
IR: 3340, 2231, 1696, 1592, 1523, 1429, 1321, 1177, 1133, 1085, 1051, 904, 840, 816,
736 cm–1 .
2-Chloro-2-methyl-N -(thiazol-2-yl)-3-tosylpropanamide (3l)
2-Chloro-2-methyl-N -(thiazol-2-yl)-3-tosylpropanamide (3l)
White solid; mp 54–56 °C; yield: 19.2 mg (54%).
1 H NMR (400 MHz, CDCl3 ): δ = 10.17 (br s, 1 H), 7.78 (d, J = 8.3 Hz, 2 H), 7.51 (d, J = 3.5 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.04 (d, J = 3.5 Hz, 1 H), 4.18 (d, J = 14.6 Hz, 1 H), 3.82 (d, J = 14.6 Hz, 1 H), 2.38 (s, 3 H), 1.97 (s, 3 H).
13 C NMR (75 MHz, CDCl3 ): δ = 167.3, 157.6, 145.4, 138.0, 137.1, 130.0 (2 C), 128.4 (2 C), 114.6, 65.3, 65.0,
30.5, 21.8.
HRMS (ESI-TOF): m /z calcd for C14 H16 ClN2 O3 S2 [M + H]+ : 359.0291; found: 359.0291.
IR: 2924, 2359, 1681, 1537, 1321, 1291, 1150, 1086, 568 cm–1 .
2-Chloro-N -phenyl-3-tosylpropanamide (3m)
2-Chloro-N -phenyl-3-tosylpropanamide (3m)
Yellow oil; yield: 17.5 mg (52%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.11 (br s, 1 H), 7.83 (d, J = 8.3 Hz, 2 H), 7.46 (dd, J = 8.6, 1.0 Hz, 2 H), 7.39–7.30 (m, 4 H), 7.17 (tt, J = 7.5, 1.4 Hz, 1 H), 4.85 (dd, J = 7.6, 4.6 Hz, 1 H), 4.20 (dd, J = 14.8, 4.6 Hz, 1 H), 3.67 (dd, J = 14.8, 7.6 Hz, 1 H), 2.43 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 163.8, 145.7, 136.67, 136.2, 130.2 (2 C), 129.3 (2 C), 128.4 (2 C), 125.6,
120.3 (2 C), 66.0, 52.3, 29.9.
HRMS (ESI-TOF): m /z calcd for C16 H16 ClNO3 SNa [M + Na]+ : 360.0437; found: 360.0442.
IR: 3336, 2924, 2853, 1701, 1677, 1601, 1549, 1500, 1446, 1321, 1148, 1086, 814, 758,
691, 520 cm–1 .
2-Chloro-3-((4-fluorophenyl)sulfonyl)-2-methyl-N -phenylpropanamide (3o)
2-Chloro-3-((4-fluorophenyl)sulfonyl)-2-methyl-N -phenylpropanamide (3o)
Yellow oil; yield: 23.0 mg (66%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.56 (br s, 1 H), 8.00–7.91 (m, 2 H), 7.51 (dd, J = 8.6, 1.1 Hz, 2 H), 7.37 (t, J = 7.9 Hz, 2 H), 7.23–7.14 (m, 3 H), 4.27 (d, J = 14.6 Hz, 1 H), 3.75 (d, J = 14.6 Hz, 1 H), 1.94 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.2, 166.4 (d, 1
J
C,F = 255.9 Hz), 136.8, 136.7 (d, 4
J
C,F = 3.1 Hz), 131.3 (d, 3
J
C,F = 9.7 Hz, 2 C), 129.3 (2 C), 125.6, 120.7 (2 C), 116.7 (d, 2
J
C,F = 22.7 Hz, 2 C), 66.4, 65.7, 31.2.
19 F NMR (376 MHz, CDCl3 ): δ = –102.9.
HRMS (ESI): m /z calcd for C16 H15 ClFNO3 SNa [M + Na]+ : 378.0343; found: 378.0345.
IR: 3358, 2342, 2357, 1683, 1597, 1534, 1493, 1444, 1325, 1237, 1146, 1084, 840, 757,
572 cm–1 .
2-Chloro-3-[(4-methoxyphenyl)sulfonyl]-2-methyl-N -phenylpropenamide (3p)
2-Chloro-3-[(4-methoxyphenyl)sulfonyl]-2-methyl-N -phenylpropenamide (3p)
Yellow oil; yield: 19.0 mg (51%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.53 (br s, 1 H), 7.85 (d, J = 8.9 Hz, 2 H), 7.50 (dd, J = 8.5, 1.0 Hz, 2 H), 7.35 (t, J = 7.9 Hz, 2 H), 7.18 (ddd, J = 8.5, 4.6, 1.6 Hz, 1 H), 6.93 (d, J = 8.9 Hz, 2 H), 4.24 (d, J = 14.6 Hz, 1 H), 3.80 (s, 3 H), 3.72 (d, J = 14.6 Hz, 1 H), 1.93 (s, 3 H).
13 C NMR (75 MHz, CDCl3 ): δ = 167.2, 164.1, 137.0, 131.9 (2 C), 130.7 (2 C), 129.2, 125.4, 120.6 (2 C), 114.9
(2 C), 66.5, 65.6, 55.8, 31.3.
HRMS (ESI-TOF): m /z calcd for C17 H18 ClNO4 SNa [M + Na]+ : 390.0543; found: 390.0546.
IR: 3356, 2928, 1677, 1593, 1530, 1496, 1442, 1321, 1139, 1086, 1023, 835, 576 cm–1 .
2-Chloro-2-methyl-3-[(4-nitrophenyl)sulfonyl]-N -phenylpropanamide (3q)
2-Chloro-2-methyl-3-[(4-nitrophenyl)sulfonyl]-N -phenylpropanamide (3q)
Brown solid; mp 135–136 °C; yield: 21.1 mg (55%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.52 (br s, 1 H), 8.33 (d, J = 8.9 Hz, 2 H), 8.13 (d, J = 8.9 Hz, 2 H), 7.48 (dd, J = 8.5, 1.0 Hz, 2 H), 7.39–7.36 (m, 2 H), 7.22–7.18 (m, 1 H), 4.36 (d, J = 14.7 Hz, 1 H), 3.79 (d, J = 14.7 Hz, 1 H), 1.95 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 166.9, 151.0, 145.9, 136.6, 129.9 (2 C), 129.3 (2 C), 125.8, 124.5 (2 C), 120.6
(2 C), 66.2, 65.6, 31.3.
HRMS (ESI-TOF): m /z calcd for C16 H15 ClN2 O5 SNa [M + Na]+ : 405.0288; found: 405.0285.
IR: 3384, 1683, 1599, 1530, 1349, 1332, 1310, 1146, 1083, 855, 758, 740, 691 cm–1 .
2-Chloro-2-methyl-3-[(3-nitrophenyl)sulfonyl]-N -phenylpropanamide (3r)
2-Chloro-2-methyl-3-[(3-nitrophenyl)sulfonyl]-N -phenylpropanamide (3r)
Yellow solid; mp 150 °C (dec.); yield: 8.3 mg (21%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.79 (t, J = 2.0 Hz, 1 H), 8.53 (br s, 1 H), 8.45–8.41 (m, 1 H), 8.29–8.24 (m, 1 H), 7.73 (t,
J = 8.0 Hz, 1 H), 7.51–7.46 (m, 2 H), 7.39–7.35 (m, 2 H), 7.23–7.17 (m, 1 H), 4.37
(d, J = 14.7 Hz, 1 H), 3.82 (d, J = 14.7 Hz, 1 H), 1.96 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 166.8, 142.6, 134.0, 131.2, 130.8, 129.4, 129.3 (2 C), 128.5, 125.8, 123.8,
120.5 (2 C), 66.2, 65.6, 31.4.
HRMS (ESI-TOF): m /z calcd for C16 H15 ClN2 O5 SNa [M + Na]+ : 405.0288; found: 405.0291.
IR: 3373, 3088, 1681, 1601, 1532, 1444, 1351, 1331, 1159, 1120, 880, 758 cm–1 .
3-[(5-Bromo-2-methoxyphenyl)sulfonyl]-2-chloro-2-methyl-N -phenylpropanamide (3s)
3-[(5-Bromo-2-methoxyphenyl)sulfonyl]-2-chloro-2-methyl-N -phenylpropanamide (3s)
White solid; mp 122–124 °C; yield: 25.5 mg (57%).
1 H NMR (400 MHz, CDCl3 ): δ = 8.52 (br s, 1 H), 7.99 (d, J = 2.5 Hz, 1 H), 7.60 (dd, J = 8.8, 2.5 Hz, 1 H), 7.48 (dd, J = 8.7, 1.2 Hz, 2 H), 7.38–7.31 (m, 2 H), 7.20–7.13 (tt, J = 7.4, 1.2 Hz, 1 H), 6.89 (d, J = 8.8 Hz, 1 H), 4.39 (d, J = 14.9 Hz, 1 H), 4.01 (d, J = 14.9 Hz, 1 H), 3.98 (s, 3 H), 1.96 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 166.8, 156.5, 138.5, 136.9, 132.7, 129.9, 129.2 (2 C), 125.5, 120.5 (2 C),
114.4, 113.0, 66.5, 63.6, 56.9, 31.1.
HRMS (ESI-TOF): m /z calcd for C17 H17 BrClNO4 SNa [M + Na]+ : 467.9648; found: 467.9652.
IR: 3355, 2939, 1683, 1597, 1528, 1476, 1440, 1318, 1271, 1135, 1060, 1013, 883, 755,
691, 518 cm–1 .
2-Chloro-2-methyl-N -phenyl-3-(thiophen-2-ylsulfonyl)propanamide (3t)
2-Chloro-2-methyl-N -phenyl-3-(thiophen-2-ylsulfonyl)propanamide (3t)
Colorless oil; yield: 24.0 mg (69%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.56 (br s, 1 H), 7.72 (dd, J = 3.8, 1.2 Hz, 1 H), 7.69 (dd, J = 5.0, 1.2 Hz, 1 H), 7.53 (d, J = 7.7 Hz, 2 H), 7.36 (t, J = 7.9 Hz, 2 H), 7.18 (t, J = 7.4 Hz, 1 H), 7.10 (dd, J = 4.9, 3.9 Hz, 1 H), 4.36 (d, J = 14.6 Hz, 1 H), 3.89 (d, J = 14.6 Hz, 1 H), 1.97 (s, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.1, 141.7, 136.9, 134.8, 134.6, 129.2 (2 C), 128.1, 125.6, 120.7 (2 C),
66.8, 66.5, 31.1.
HRMS (ESI-TOF): m /z calcd for C14 H14 ClNO3 S2 Na [M + Na]+ : 366.0001; found: 366.0005.
IR: 3362, 1683, 1599, 1532, 1444, 1325, 1142, 1016, 757, 691, 596 cm–1 .
3-(Butylsulfonyl)-2-chloro-2-methyl-N -phenylpropanamide (3u)
3-(Butylsulfonyl)-2-chloro-2-methyl-N -phenylpropanamide (3u)
White solid; mp 94–96 °C; yield: 17.7 mg (56%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.55 (br s, 1 H), 7.53 (d, J = 7.8 Hz, 2 H), 7.36 (t, J = 7.8 Hz, 2 H), 7.21–7.15 (m, 1 H), 4.10 (d, J = 14.8 Hz, 1 H), 3.60 (d, J = 14.8 Hz, 1 H), 3.14–3.04 (m, 2 H), 1.99 (s, 3 H), 1.89–1.75 (m, 2 H), 1.46 (sext,
J = 7.4 Hz, 2 H), 0.94 (t, J = 9.0 Hz, 3 H).
13 C NMR (75 MHz, CDCl3 ): δ = 167.5, 136.8, 129.3 (2 C), 125.6, 120.8 (2 C), 66.6, 62.3, 56.1, 31.2, 23.9,
21.8, 13.7.
HRMS (ESI-TOF): m /z calcd for C14 H20 ClNO3 SNa [M + Na]+ : 340,0750; found: 340.0753.
IR: 3355, 2961, 2933, 1979, 1597, 1530, 1442, 1318, 1127, 754, 691, 507 cm–1 .
2-Chloro-3-(isopropylsulfonyl)-2-methyl-N -phenylpropanamide (3v)
2-Chloro-3-(isopropylsulfonyl)-2-methyl-N -phenylpropanamide (3v)
Yellow oil; yield: 19.5 mg (64%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.56 (br s, 1 H), 7.53 (d, J = 7.6 Hz, 2 H), 7.36 (t, J = 7.9 Hz, 2 H), 7.17 (t, J = 7.4 Hz, 1 H), 4.10 (d, J = 14.4 Hz, 1 H), 3.58 (d, J = 14.4 Hz, 1 H), 3.23 (hept, J = 6.9 Hz, 1 H), 2.00 (s, 3 H), 1.41 (d, J = 2.1 Hz, 3 H), 1.38 (d, J = 2.1 Hz, 3 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.6, 136.9, 129.3 (2 C), 125.6, 120.9 (2 C), 66.4, 58.9, 56.0, 31.3, 15.4,
15.2.
HRMS (ESI-TOF): m /z calcd for C13 H18 ClNO3 SNa [M + Na]+ : 326.0594; found: 326.0594.
IR: 3355, 2984, 2935, 2361, 1679, 1597, 1531, 1444, 1312, 1123, 881, 755, 691 cm–1 .
2-Chloro-3-(cyclopropylsulfonyl)-2-methyl-N -phenylpropanamide (3w)
2-Chloro-3-(cyclopropylsulfonyl)-2-methyl-N -phenylpropanamide (3w)
White solid; mp 108–110 °C; yield: 27.0 mg (90%).
1 H NMR (300 MHz, CDCl3 ): δ = 8.58 (br s, 1 H), 7.53 (d, J = 8.4 Hz, 2 H), 7.36 (t, J = 7.9 Hz, 2 H), 7.20–7.15 (m, 1 H), 4.22 (d, J = 14.7 Hz, 1 H), 3.70 (d, J = 14.7 Hz, 1 H), 2.61 (tt, J = 8.0, 4.8 Hz, 1 H), 1.99 (s, 3 H), 1.32–1.24 (m, 2 H), 1.04 (d, J = 8.0 Hz, 2 H).
13 C NMR (101 MHz, CDCl3 ): δ = 167.5, 136.9, 129.2 (2 C), 125.6, 120.8 (2 C), 66.6, 63.7, 32.7, 31.1, 5.6,
5.5.
HRMS (ESI-TOF): m /z calcd for C13 H16 ClNO3 SNa [M + Na]+ : 324.0437; found: 324.0437.
IR: 3356, 2359, 1681, 1597, 1531, 1444, 1321, 1131, 885, 757, 576, 507 cm–1 .
