Synthesis of Sulfonamide-Based Ynamides and Ynamines in Water

Article abstract of DOI:10.1021/acs.joc.0c02326

Ynamides, though relatively more stable than ynamines, are still moisture-sensitive and prone to hydration especially under acidic and heating conditions. Here we report an environmentally benign, robust protocol to synthesize sulfonamide-based ynamides and arylynamines via Sonogashira coupling reactions in water, using a readily available quaternary ammonium salt as the surfactant.

Full text of DOI:10.1021/acs.joc.0c02326

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Synthesis of Sulfonamide-Based Ynamides and Ynamines in Water
Lei Zhao, Hongyi Yang, Ruikun Li, Ye Tao, Xiao-Feng Guo, Edward A. Anderson, Andrew Whiting,
and Na Wu*
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ABSTRACT: Ynamides, though relatively more stable than ynamines, are still moisture-
sensitive and prone to hydration especially under acidic and heating conditions. Here we
report an environmentally benign, robust protocol to synthesize sulfonamide-based
ynamides and arylynamines via Sonogashira coupling reactions in water, using a readily
available quaternary ammonium salt as the surfactant.
he “greening” of global chemical processes has become a
aryl ynamines,8 which exempts from employing halo-alkynes,9
via copper-free Sonogashira coupling reactions in water.
To explore the balance of reactivity and stability of ynamides
in water, we chose the most stable class of ynamides
sulfonamide-based ynamide 5aas a model substrate. To
avoid the homocoupling side reaction of terminal ynamides to
1,3-diynediamides instead of cross coupling,10 we studied
copper-free variations of the Sonogashira coupling reaction,11
using different bases and palladium sources under the standard
conditions (Table 1).
T
major concern in the chemical industry.1 As a nontoxic,
inexpensive, benign, and renewable solvent for organic
synthesis, water has been of widespread interest in recent
years.2 Ynamides, an attractive class of alkynes activated by the
electron-donating ability of an amide nitrogen atom adjacent
to an alkyne, are versatile functional groups that find use as
fascinating building blocks for the synthesis of nitrogen-
containing compounds.3 However, the preparation of
ynamides typically involves dry organic solvents.4 This is
because of ynamides’ moisture-sensitivity, which can lead to
decomposition and hydration of ynamides upon heating/acid-
catalyzed/transition-metal-catalyzed conditions (Figure 1),5,6
Gratifyingly, no diyne was observed under these conditions,
although the desired coupling was accompanied by decom-
position and/or hydrolysis of 5a. An initial screen of bases
a
Table 1. Copper-Free Sonogashira Coupling Conditions
b
yield
entry
Pd
PdCl2
PdCl2
base (equiv)
solvent
(%)
1
2
Et3N (2)
Et3N (2)
THF
THF
12
18
Cs2CO3 (1)
Et3N (2)
Et3N (2)
Cs2CO3 (2)
Cs2CO3 (2)
Cs2CO3 (2)
c
3
4
5
6
7
PdCl2
H2O
THF
THF
H2O
N.R.
30
93
11
70
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Figure 1. Hydrolysis of ynamides.5
THF/H2O (v/v = 1/3)
as well as because of ynamides’ insolubility in water, and as a
result, water does not function as an efficient reaction medium.
Recently, the development of micellar catalysis and the
surfactants is revolutionizing chemical synthesis and catalysis
in aqueous media, leading to an important benchtop
alternative to the employment of organic solvents.7a−c
Consequently, the investigation of ynamides’ reactions
conducted in aqueous media has attracted attention.7d−f
Herein, with implicit challenge on possible hydration of the
starting materials (terminal ynamides) and products (internal
ynamides), we report the synthesis of ynamides, and less stable
a
5a (0.2 mmol), 7a (0.2 mmol), Et3N (0.056 mL) or Cs2CO3 (0.13
b
c
g), solvent (4 mL), 60 °C, 10 h, N2. Isolated yield. N.R. = no
reaction.
Received: September 30, 2020
https://dx.doi.org/10.1021/acs.joc.0c02326
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
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The Journal of Organic Chemistry
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Note
showed that Cs2CO3 (as opposed to an organic base) is crucial
to achieve high yields in THF (Table 1, entry 5). In entry 6,
5a’s hydrolyzed byproduct N-phenyl-N-tosylacetamide was
isolated in 43% yield. We hypothesized that the main drawback
in the use of water (low solubility, hydrolysis/decomposition
of ynamides) could be overcome by using a surfactant, which
might solubilize the ynamide or form emulsions.12 In micellar
solution, ynamides could be protected from hydrolysis by
location at the hydrophobic core of micelle droplets, thus
retarding decomposition in water. With the optimized base in
hand (Cs2CO3), we therefore investigated ionic liquids and the
effects of surfactants/phase transfer agents on Sonogashira
coupling reactions to access ynamides 8aa in water (Table
2).13
based micellar solution (Table 2, entries 16−21). They were
again accompanied by hydrolysis of 5a.
With optimized conditions in hand, we next investigated the
scope of the aryl iodide coupling partner (Table 3). We were
a
Table 3. Substrate Scope with Respect to Aryl Iodide
Table 2. Optimization of Additives for Ynamide Synthesis in
a
Water
b
entry
ionic liquid (mL)
base (equiv)
yield (%)
1
2
3
4
5
[BMIm][BF4] (0.6)
[BMIm][BF4] (2)
[BMIm][BF4] (neat)
[BMIm][PF6] (0.6)
[BMIm][PF6] (2)
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
14
41
N.R.
c
d
38
41
43
c
6
[BMIm][PF6] (neat)
surfactant (g)
a
b
c
5a (0.24 mmol), 7 (0.2 mmol). Isolated yield. 48 h.
b
entry
base (equiv)
yield (%)
7
8
9
10
11
12
13
14
SDS (0.02)
SDS (1)
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
t-BuOK
KOH
10
39
14
64
84
63
36
49
32
50
25
31
27
22
16
delighted to find that aryl iodides featuring both electron-
donating groups (EDG) and electron-withdrawing groups
(EWG) were all well accommodated, affording internal
ynamides 8aa−8al in good to excellent yields (Table 3, entries
1−11). Noticeably, aryl iodides bearing strong EDGs such as
methoxy and acetamide proved to be outstanding substrates,
affording electron-rich ynamides which are relatively prone to
hydrolysis5c,14 yet are compatible with the reaction conditions
(Table 3, entries 2−4).
CTAB (0.02)
CTAB (1)
CTAB (2)
CTAB (4)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
CTAB (2)
e
f
g
15
16
17
18
19
20
21
Similarly, heterocyclic aryl iodides proved to be highly
suitable substrates (Table 3, entries 5−7). The Sonogashira
coupling of bicyclic aryl iodides was also successful, with
quinolinyl 8ah (entry 7) and naphthyl 8am (entry 12)
obtained in good yields. The configuration of 8aj was
confirmed by X-ray crystallographic analysis.15
TBAF·3H2O
CsF
NH4OAc
NH3·H2O
a
5a (0.2 mmol), 7a (0.2 mmol), Cs2CO3 (0.13 g), water (4 mL), 60
b
c
d
°C, 10 h, N2. Isolated yield. No water was employed. N.R. = no
e
f
Encouraged by these results, we next evaluated the scope of
the ynamide substituent (Table 4). Compared with aryl
ynamides, alkyl ynamides are more nucleophilic and thus could
be more reactive toward hydrolysis in H2O.16 To our delight,
both acyclic and cyclic alkyl ynamides were compatible with
the standard reaction conditions, affording Sonogashira
product 8 in good to excellent yields (Table 4, entries 1−9).
A range of acyclic ynamides proved effective in the coupling
reactions, including those bearing primary and secondary alkyl
substituents (Table 4, entries 2−4), whereas tertiary alkyl (t-
Bu) ynamides gave a complex mixture of products.
Interestingly, the high ring strain of cyclic counterparts
enabled productive formation of 8fa and 8ga in excellent
yields as well. We presume that the increased nucleophilicity of
the alkyl-substituted ynamide would be beneficial on the
coupling and therefore enable effective conversion of starting
materials to internal ynamides, as we were gratified to find out
that hydrolyzed byproducts have been diminished with few
reaction. The reaction was conducted at 40 °C. The reaction was
g
conducted at 80 °C. The reaction was conducted at 100 °C.
[BMIm][BF4] = 1-Butyl-3-methylimidazolium tetrafluoroborate.
[BMIm][PF6] = 1-Butyl-3-methylimidazolium hexafluorophosphate.
SDS = Sodium dodecyl sulfate. CTAB = Cetrimonium bromide.
Investigations into the effect of ionic liquids or surfactants
revealed that, compared to the previous optimum conditions
(Table 1, entry 6), the coupling yield was improved to 84%
(Table 2, entry 11). No hydrolysis of either the terminal
ynamide or product internal ynamide was observed, with the
highest yield obtained using 0.5 g/mL of readily available,
cheap cetrimonium bromide (CTAB) in water at 60 °C. Lower
temperatures led to reduced yields, and competing hydrolysis
of 5a was observed (e.g., 26% of N-phenyl-N-tosylacetamide in
entry 13), while higher temperatures induced rapid decom-
position of 5a (Table 2, entries 14 and 15). Other inorganic
bases were investigated and proved less effective in CTAB-
B
https://dx.doi.org/10.1021/acs.joc.0c02326
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Note
Table 4. Substrate Scope with Respect to Terminal
Ynamide
Scheme 1
a
drop in reaction yield to some extent, by a factor of the
viscosity of surfactant which prevents the stirring bar from
spinning rapidly and consequently reduces biphase particle
collision. Scalability is challenging associated with the scaling-
up of the developed protocol.
In order to explore the further development of their
application, transformations of ynamide 5a in H2O were
studied to explore the generality of aqueous synthetic
procedures. Copper-catalyzed coupling of 5a with allyl chloride
under mild, aqueous conditions afforded allylic ynamide 9a in
quantitative yield (Scheme 2a). Interestingly, our currently
Scheme 2. Versatile Functionalizations of Ynamide
developed robust, affordable, and procedurally simple aqueous
procedure allows for convenient hydroacyloxylation of the
ynamide in excellent yield with trace amount of hydration
sideproduct N-phenyl-N-tosylacetamide observed (Scheme
2b), as well as hydro-diithiophosphonylation of ynamide 5a
in moderate yield (Scheme 2c).18
An inexpensive, green, and convenient method to access
internal ynamides has been developed that overcomes
problematic hydrolysis encountered with other ynamide-
forming procedures and provides a reliable means to prepare
a diverse range of internal ynamides with extensive substituent
variation. The strategy can access sulfonamide-based ynamides
and aryl ynamines without requiring anhydrous conditions.
The mild yet robust reaction conditions and the simple and
cheap procedure may allow this synthesis to be extended to
chemistry and materials science applications in both academic
and industrial research settings.
a
b
c
d
5 (0.24 mmol), 7a (0.2 mmol). Isolated yield. 48 h. Hydrolysis.
e
Decomposition. For 5q, DABCO, Et3N, and Cs2CO3 have all been
tested, respectively.
decompositions observed in entries 5, 6, and 9. Even more
complex natural product (rosin)-based ynamides could be
prepared in outstanding yield (entry 10). Exploration of the
ynamide electron-withdrawing group led to further interesting
results: Coupling of Ms- and Ns-ynamides was accomplished
in good yields (entries 11 and 12), while aryl ynamines, which
display higher reactivity and less stability toward hydrolysis,8,17
accessed internal aryl ynamines in moderate yields (entries 13
and 14). Some limitations were observed when using ester-
substituted ynamides (Boc-, oxazolidone-) and other electron-
rich aryl ynamines (5r, 5s), none of which provided the desired
coupling products.
EXPERIMENTAL SECTION
■
General Information. Reactions were performed in the presence
of nitrogen applying the Schlenk line technique unless otherwise
stated. Commercially available reagents were used throughout without
further purification other than those detailed below. THF (AR) was
distilled over sodium benzophenone ketyl under nitrogen, and H2O
was deionized water purified by a combination of the two methods
reverse osmosis and ion-exchange resin. 1H NMR and 13C NMR
spectra were recorded using a Bruker Advance 400 spectrometer
1
operating at 400 MHz for H NMR and at 100 MHz for 13C NMR,
1
using a Bruker Advance 500 spectrometer at 500 MHz for H NMR
and at 125 MHz for 13C NMR, or using a Bruker Advance 600
Ynamine 5n was applied on a gram scale to test the
reproducibility of the reaction (Scheme 1). It resulted in a
1
spectrometer at 600 MHz for H NMR and at 150 MHz for 13C
C
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Note
NMR. CDCl3 and (CD3)2CO were used as the solvents for all
samples. H NMR chemical shifts are reported using residual proton
fonamide (1.13 g, 5 mmol); silica gel purification (3.5 cm × 14 cm,
ethyl acetate/petroleum ether = 1:80, Rf = 0.70 (EtOAc/PE = 1:5));
yield: 69% (0.859 g, yellowish oil); H NMR (600 MHz, CDCl3) δ
7.69 (d, 2H, J = 8.3 Hz), 7.24 (d, 2H, J = 8.0 Hz), 4.26 (quintd, 1H, J1
= 8.4 Hz, J2 = 0.6 Hz), 2.80 (s, 1H), 2.34 (s, 3H), 2.11−2.04 (m, 2H),
1.93−1.88 (m, 2H), 1.56−1.46 (m, 2H); 13C{1H} NMR (150 MHz,
CDCl3) δ 144.7, 134.9, 129.7, 127.4, 73.5, 61.5, 53.0, 28.0, 21.5, 14.3;
1
on non-deuterated solvent (CDCl3: 7.26 ppm), whereas 13C NMR
spectra are reported using the carbon signals of the deuterated solvent
(CDCl3: 77.16 ppm). Product spots were visualized by UV light at
254 nm and subsequently developed using potassium permanganate
solution as appropriate. All chromatography was carried out using
silica gel (300−400 mesh) obtained from Qingdao Puke company.
The removal of solvent was performed on a rotary evaporator in a
vacuum. IR spectra were recorded in the range 4000−400 cm−1 on a
PerkinElmer Spectrum FT/IR spectrometer using a KBr pellet.
Melting points were determined using an electrothermal melting
point apparatus, INESA SGWX-4B. High resolution mass spectrom-
etry was carried out on a new ultraflextreme equipped with a TOF/
TOF/Ultimate 3000 Nano HPLC. Room temperature range is
around 25−34 °C.
1
FT-IR (KBr) υ 3283, 2945, 2865, 2060, 1598, 1361, 1168, 1086, 814,
̅
667, 547 cm−1; HRMS (ESI+) m/z calcd for C13H16NO2S+ [M + H]+
250.0902 found 250.0903.
N-Cyclopentyl-N-ethynyl-4-methylbenzenesulfonamide (5h).
(Table 4, entry 7) Prepared from N-cyclopentyl-4-methylbenzene-
sulfonamide (1.19 g, 5 mmol); silica gel purification (3.5 cm × 14 cm,
ethyl acetate/petroleum ether = 1:80, Rf = 0.70 (EtOAc/PE = 1:5));
1
yield: 56% (0.737 g, yellowish oil); H NMR (600 MHz, CDCl3) δ
7.79 (d, 2H, J = 8.2 Hz), 7.33 (d, 2H, J = 8.2 Hz), 4.21 (quint, 1H, J =
7.8 Hz), 2.78 (s, 1H), 2.43 (s, 3H), 1.75−1.70 (m, 2H), 1.66−1.60
(m, 2H), 1.59−1.54 (m, 2H), 1.48−1.43 (m, 2H); 13C{1H} NMR
(150 MHz, CDCl3) δ 144.7, 135.4, 129.8, 127.6, 73.9, 61.2, 60.6, 29.9,
Experimental Procedures of Synthesizing Terminal Yna-
mides. Ynamides 5a,19 5b,19 5c,20 5d,21 5e,22 5j,23 and 5n24 were
prepared as described previously, using procedures based upon the
methodology originally described by Anderson and co-workers.4e
Cycloheptyl-N-ethynyl-4-methylbenzenesulfonamide (5j).
(Table 4, entry 9) Prepared from (E)-N-cycloheptyl-N-(1,2-
dichlorovinyl)-4-methylbenzenesulfonamide (1.11 g, 3.1 mmol); silica
gel purification (3.5 cm × 14 cm, ethyl acetate/petroleum ether =
1:50, Rf = 0.51 (EtOAc/PE = 1:5)); yield: 64% (0.578 g, colorless
oil); 1H NMR (500 MHz, CDCl3) δ 7.79 (d, 2H, J = 8.3 Hz), 7.32 (d,
2H, J = 8.0 Hz), 3.88−3.84 (m, 1H), 2.76 (s, 1H), 2.43 (s, 3H),
1.71−1.67 (m, 4H), 1.65−1.59 (m, 2H), 1.56−1.49 (m, 2H), 1.47−
1.42 (m, 2H), 1.39−1.33 (m, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 144.5, 136.0, 129.8, 127.4, 74.3, 61.4, 60.6, 33.3, 27.8, 24.2,
24.0, 21.7; FT-IR (KBr) υ 3292, 2961, 2871, 2129, 1598, 1362, 1168,
̅
1091, 814, 663, 591, 547 cm−1; HRMS (ESI+) m/z calcd for
C14H17NNaO2S+ [M + Na]+ 286.0878 found 286.0879.
N-Cyclohexyl-N-ethynyl-4-methylbenzenesulfonamide (5i).
(Table 4, entry 8) Prepared from N-cyclohexyl-4-methylbenzenesul-
fonamide (1.27 g, 5 mmol); silica gel purification (3.5 cm × 14 cm,
ethyl acetate/petroleum ether = 1:50, Rf = 0.52 (EtOAc/PE = 1:5));
1
yield: 43% (0.637 g, yellowish oil); H NMR (400 MHz, CDCl3) δ
7.78 (d, 2H, J = 8.2 Hz), 7.29 (d, 2H, J = 8.1 Hz), 3.71−3.65 (m,
1H), 2.76 (s, 1H), 2.40 (s, 3H), 1.78−1.68 (m, 3H), 1.61−1.53 (m,
3H), 1.49−1.43 (m, 2H), 1.28−1.19 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.5, 136.2, 129.8, 127.4, 73.8, 60.8, 59.0, 30.8, 25.4,
21.7; FT-IR (KBr) υ 2930, 2860, 2131, 1597, 1364, 1168, 971, 814,
̅
662, 592 cm−1; HRMS (ESI+) m/z calcd for C16H21NNaO2S+ [M +
Na]+314.1191 found 314.1188. Its spectroscopic data is consistent
with a literature report.23
24.8, 21.6; FT-IR (KBr) υ 3318, 2940, 2865, 2128, 1454, 1363, 1165,
̅
883, 813, 664, 593 cm−1; HRMS (ESI+) m/z calcd for
C15H19NNaO2S+ [M + Na]+ 300.1034 found 300.1037. Its
spectroscopic data is consistent with a literature report.24
Ethynyl-N-dehydroabietyl-4-methylbenzenesulfonamide (5k).
(Table 4, entry 10) Prepared from (E)-N-dehydroabietyl-N-(1,2-
dichlorovinyl)-4-methylbenzenesulfonamide (2.56 g, 4.79 mmol);
silica gel purification (3.5 cm × 14 cm, ethyl acetate/petroleum ether
= 1:50, Rf = 0.54 (EtOAc/PE = 1:5)); yield: 44% (0.982 g, beige
solid); mp 116.2−117.3 °C; 1H NMR (500 MHz, CDCl3) δ 7.82 (d,
2H, J = 8.3 Hz), 7.36 (d, 2H, J = 8.0 Hz), 7.19 (d, 1H, J = 8.2 Hz),
7.01 (dd, 1H, J1 = 8.2 Hz, J2 = 1.7 Hz), 6.89 (s, 1H), 3.22 (d, 2H, J =
2.8 Hz), 2.98−2.93 (m, 1H), 2.89 (d, 1H, J = 5.9 Hz), 2.84 (dt, 1H, J1
= 13.8 Hz, J2 = 6.8 Hz), 2.66 (s, 1H), 2.47 (s, 3H), 1.86−1.82 (m,
1H), 1.80−1.66 (m, 6H), 1.60−1.57 (m, 1H), 1.45 (dt, 1H, J1 = 12.1
Hz, J2 = 4.5 Hz), 1.26−1.23 (m, 9H), 1.03 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 147.2, 145.7, 144.8, 134.7, 134.4, 129.8, 128.1,
126.9, 124.1, 123.9, 79.4, 62.6, 58.3, 44.6, 39.0, 38.2, 37.7, 36.5, 33.6,
9-Ethynyl-9H-carbazole (5o). (Table 4, entry 14) Prepared from
9H-carbazole (0.334 g, 2 mmol); silica gel purification (2 cm × 14
cm, petroleum ether, Rf = 0.6 (PE)); yield: 49% (0.186 g, colorless
oil); 1H NMR (400 MHz, CDCl3) δ 8.05 (d, 2H, J = 7.8 Hz), 7.71 (d,
2H, J = 8.1 Hz), 7.56 (m, 2H, J1 = 7.2 Hz, J2 = 1 Hz), 7.38 (td, 2H, J1
= 7.3 Hz, J2 = 0.8 Hz), 3.48 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 140.5, 126.9, 123.6, 122.3, 120.5, 111.4, 72.9, 62.8; FT-IR
(KBr) υ 3304, 2924, 2149, 1480, 1450, 1345, 1225, 747, 573 cm−1;
̅
HRMS (ESI+) m/z calcd for C14H10N+ [M + H]+ 192.0813 found
192.0799. Its spectroscopic data is consistent with a literature
report.23
General Procedure of Witulski Rearragement Using
Iodoalkynyl Salt to Synthesize Terminal Ynamides. Ynamides
5l,21 5m,27 5r,28 and 5s29 were prepared as described previously, using
procedures based upon the methodology originally described by
Witulski and co-workers.30
29.7, 25.8, 24.1, 21.8, 19.2, 18.8, 18.6; FT-IR (KBr) υ 3314, 2956,
̅
2869, 2132, 1368, 1170, 815, 731, 657, 588, 546 cm−1; HRMS (ESI+)
m/z calcd for C29H37NNaO2S+ [M + Na]+ 486.2443 found 486.2447.
Experimental Procedures of Copper-Catalyzed C−N Cou-
pling to Synthesize Terminal Ynamides. Ynamides 5f,23 5i,24
5o,23 5p,25 and 5q21 were prepared as described previously, using
procedures based upon the methodology originally described by
Hsung and co-workers.26
N-Ethynyl-N-phenylmethanesulfonamide (5l). (Table 4, entry
11) Prepared from N-phenylmethanesulfonamide (1.1 g, 4 mmol);
silica gel purification (3.5 cm × 14 cm, ethyl acetate/petroleum ether
= 1:50, Rf = 0.5 (EtOAc/PE = 1:5)); yield: 30% (0.234 g, yellowish
1
prisms); mp 78.5−79.3 °C; H NMR (500 MHz, CDCl3) δ 7.53−
N-Cyclopropyl-N-ethynyl-4-methylbenzenesulfonamide (5f).
(Table 4, entry 5) Prepared from N-cyclopropyl-4-methylbenzene-
sulfonamide (1.1 g, 5 mmol); silica gel purification (3.5 cm × 14 cm,
ethyl acetate/petroleum ether = 1:70, Rf = 0.67 (EtOAc/PE = 1:5));
yield: 64% (0.752 g, orange oil); 1H NMR (400 MHz, CDCl3) δ 7.73
(d, 2H, J = 8.4 Hz), 7.27 (d, 2H, J = 8.0 Hz), 2.65 (s, 1H), 2.64−2.60
(m, 1H), 2.35 (s, 3H), 0.76−0.70 (m, 2H), 0.69−0.63 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 145.0, 133.7, 129.7, 127.9, 75.5,
7.51 (m, 2H), 7.44 (tt, 2H, J1 = 7.4 Hz, J2 = 1.6 Hz), 7.37 (tt, 1H, J1 =
7.3 Hz, J2 = 1.2 Hz), 3.12 (s, 3H), 2.97 (s, 1H); 13C{1H} NMR (125
MHz, CDCl3) δ 138.1, 129.6, 128.7, 125.7, 75.9, 59.8, 36.8; FT-IR
(KBr) υ 2922, 2150, 1490, 1360, 1166, 963, 767, 695, 515; HRMS
̅
(ESI+) m/z calcd for C9H10NO2S+ [M + H]+ 196.0432 found
196.0433. Its spectroscopic data is consistent with a literature
report.21
N-Ethynyl-para-nitro-N-phenylbenzenesulfonamide (5m).
(Table 4, entry 12) Prepared from 4-nitro-N-phenylbenzenesulfona-
mide (1.0 g, 3.6 mmol); silica gel purification (3.5 cm × 14 cm, ethyl
acetate/petroleum ether = 1:50, Rf = 0.5 (EtOAc/PE = 1:5)); yield:
58.9, 32.4, 21.6, 6.4; FT-IR (KBr) υ 3319, 2944, 2867, 1464, 1370,
̅
1173, 883, 813, 678, 576 cm−1; HRMS (ESI+) m/z calcd for
C12H14NO2S+ [M + H]+ 236.0745 found 236.0747. Its spectroscopic
data is consistent with a literature report.23
1
21% (0.285 g, yellowish solid); mp 139.8−140.8 °C; H NMR (500
N-Cyclobutyl-N-ethynyl-4-methylbenzenesulfonamide (5g).
(Table 4, entry 6) Prepared from N-cyclobutyl-4-methylbenzenesul-
MHz, CDCl3) δ 8.35 (dt, 2H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.89 (dt, 2H,
J1 = 9.0 Hz, J2 = 2.4 Hz), 7.38−7.35 (m, 3H), 7.25−7.23 (m, 2H),
D
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Note
2.90 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 151.0, 141.1,
137.6, 129.6, 129.2, 126.2, 124.3, 75.6, 59.9 (one carbon signal is
1595, 1489, 1454, 1374, 1174, 1089, 814, 692, 665, 580 cm−1; HRMS
(ESI+) m/z calcd for C22H19NNaO2S+ [M + Na]+ 384.1034 found
384.1039.
missing due to the overlapping); FT-IR (KBr) υ 2927, 2856, 2242,
̅
1698, 1534, 1349, 1182, 1088, 803, 692, 607, 577 cm−1; HRMS
(ESI+) m/z calcd for C14H11N2O4S+ [M + H]+ 303.0434 found
303.0428. Its spectroscopic data is consistent with a literature
report.27
N-((4-Methoxyphenyl)ethynyl)-4-methyl-N-phenylbenzenesulfo-
namide (8ac). (Table 3, entry 2) Prepared from ynamide 5a (65.1
mg, 0.24 mmol) and 7c (0.0468 g, 0.2 mmol); silica gel purification (2
cm × 14 cm, ethyl acetate/petroleum ether = 1:50, then 1:30, Rf = 0.4
(EtOAc/PE = 1:5)); yield: 96% (0.0725 g, yellowish acicular solid);
mp 106.9−107.9 °C; 1H NMR (500 MHz, d6-acetone) δ 7.64 (d, 2H,
J = 8.3 Hz), 7.46 (d, 2H, J = 8 Hz), 7.44−7.40 (m, 2H), 7.40−7.36
(m, 3H), 7.34−7.33 (m, 2H), 6.93 (dt, 2H, J1= 8.9 Hz, J2 = 2.1 Hz),
3.81 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz, d6-acetone) δ
160.9, 146.3, 140.1, 134.1, 134.0, 130.6, 130.1, 129.1, 129.0, 126.8,
1-Ethynyl-1H-benzoimidazole (5r). Prepared from benzimidazole
(1.07 g, 9.1 mmol); silica gel purification (3.5 cm × 14 cm, ethyl
acetate/petroleum ether = 1:20, Rf = 0.4 (EtOAc/PE = 1:5)); yield:
11% (0.142 g, white crystalline solid); 1H NMR (400 MHz, CDCl3) δ
8.08 (s, 1H), 7.81 (d, 1H, J = 7.4 Hz), 7.58 (dd, 1H, J1 = 7.8 Hz, J2 =
0.6 Hz), 7.40 (td, 1H, J1 = 7.4 Hz, J2 = 1.0 Hz), 7.35 (td, 1H, J1 = 7.4
Hz, J2 = 1.1 Hz), 3.30 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
143.7, 141.9, 134.4, 125.0, 124.2, 120.9, 111.0, 70.3, 62.2. Its
spectroscopic data is consistent with a literature report.28
115.05, 115.03, 82.4, 71.0, 55.7, 21.5; FT-IR (KBr) υ 2926, 2855,
̅
2237, 1708, 1596, 1488, 1370, 1172, 1088, 814, 694, 565 cm−1;
HRMS (ESI+) m/z calcd for C22H20NO3S+ [M + H]+ 378.1164 found
378.1167.
1-Ethynyl-1H-benzotriazole (5s). Prepared from benzotriazole
(0.74 g, 6.25 mmol); silica gel purification (3.5 cm × 14 cm, ethyl
acetate/petroleum ether = 1:20, Rf = 0.4 (EtOAc/PE = 1:5)); yield:
N-((2-Methoxyphenyl)ethynyl)-4-methyl-N-phenylbenzenesulfo-
namide (8ad). (Table 3, entry 3) Prepared from ynamide 5a (65.1
mg, 0.24 mmol) and 7d (26 μL, 0.2 mmol); silica gel purification (2
cm × 14 cm, ethyl acetate/petroleum ether = 1:50, then 1:30, Rf = 0.4
1
16% (0.143 g, yellow prisms); mp 71.0−72.0 °C; H NMR (500
MHz, CDCl3) δ 8.11 (d, 1H, J = 8.4 Hz), 7.67 (d, 1H, J = 8.3 Hz),
7.63 (td, 1H, J1 = 6.9 Hz, J2 = 0.6 Hz), 7.46 (td, 1H, J1 = 7.1 Hz, J2 =
0.9 Hz), 3.84 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 143.8,
134.4, 129.7, 125.5, 120.7, 110.0, 69.6, 68.7. Its spectroscopic data is
consistent with a literature report.29
1
(EtOAc/PE = 1:5)); yield: 82% (0.0617 g, yellowish oil); H NMR
(500 MHz, d6-acetone) δ 7.71 (dt, 2H, J1= 10.5 Hz, J2 = 2.2 Hz), 7.46
(d, 2H, J = 10.2 Hz), 7.44−7.40 (m, 2H), 7.39−7.34 (m, 4H), 7.34−
7.31 (m, 1H), 7.03 (d, 1H, J = 8.2 Hz), 6.93 (td, 1H, J1= 9.5 Hz, J2 =
1.2 Hz), 3.89 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz, d6-
acetone) δ 161.2, 146.3, 134.0, 133.8, 133.7, 130.6, 130.5, 130.0,
129.13, 129.06, 126.7, 121.2, 112.5, 111.9, 87.4, 67.8, 56.1, 21.5; FT-
General Procedure of Sonogashira Coupling to Access
Internal Ynamides/Ynamines in Water.
IR (KBr) υ 2925, 2854, 2239, 1713, 1596, 1492, 1463, 1371, 1248,
̅
1173, 1089, 1025, 813, 753, 693, 577, 546 cm−1; HRMS (ESI+) m/z
calcd for C22H20NO3S+ [M + H]+ 378.1164 found 378.1165.
N-(4-((4-Methyl-N-phenylphenylsulfonamido)ethynyl)phenyl)-
acetamide (8ae). (Table 3, entry 4) Prepared from ynamide 5a (65.1
mg, 0.24 mmol) and 7e (0.0522 g, 0.2 mmol); silica gel purification
(2 cm × 14 cm, ethyl acetate/petroleum ether = 1:2, Rf = 0.5
(EtOAc/PE = 1:1)); yield: 92% (0.0748 g, orange acicular solid); mp
136.2−137.5 °C; 1H NMR (500 MHz, CDCl3) δ 7.68 (brs, 1H), 7.61
(d, 2H, J = 8.3 Hz), 7.49 (d, 2H, J = 8.5 Hz), 7.36−7.33 (m, 3H),
7.32−7.27 (m, 6H), 2.45 (s, 3H), 2.16 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 168.7, 145.2, 139.0, 138.1, 133.0, 132.6, 129.7, 129.2,
128.40, 128.38, 126.4, 119.6, 118.0, 82.5, 70.4, 24.7, 21.8; FT-IR
To a solution of ynamide/ynamine 5 (0.24 mmol) and aryl
iodide 7 (0.2 mmol) in water (4 mL) in a 10 mL Schlenk tube
was charged Pd(PPh3)4 (12 mg), Cs2CO3 (0.13 g), and
cetrimonium bromide (2 g). After being stirred at 60 °C under
nitrogen protection overnight using a heating mantle, the
reaction mixture was extracted with EtOAc (3 × 20 mL). The
combined organic layer was washed with brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified
by column chromatography on silica gel to afford internal
ynamide/ynamine 8.
(KBr) υ 2926, 2855, 2222, 1673, 1596, 1524, 1490, 1369, 1316, 1165,
̅
1090, 814, 695, 666, 579 cm−1; HRMS (ESI+) m/z calcd for
Note: Some ynamides/ynamines are relatively less stable and
hydrolyze in both CDCl3 and d6-acetone. The effective component of
ynamide/ynamine 5 is 1 equiv, as they hydrolyzed partially (∼10%)
before the reaction was set up.
C23H20N2NaO3S+ [M + Na]+427.1092 found 427.1090.
4-Methyl-N-phenyl-N-(pyridin-3-ylethynyl)benzenesulfonamide
(8af). (Table 3, entry 5) Prepared from ynamide 5a (65.1 mg, 0.24
mmol) and 7f (26 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:30, then 1:10, Rf = 0.3
(EtOAc/PE = 1:5)); yield: 69% (0.0484 g, orange solid); mp 116.5−
Methyl-N-phenyl-N-(phenylethynyl)benzenesulfonamide (8aa).
Prepared from ynamide 5a (65.1 mg, 0.24 mmol) and 7a (22 μL,
0.2 mmol); silica gel purification (2 cm × 14 cm, ethyl acetate/
petroleum ether = 1:50, Rf = 0.54 (EtOAc/PE = 1:5)); yield: 84%
1
117.7 °C; H NMR (500 MHz, CDCl3) δ 8.60 (d, 1H, J = 1.4 Hz),
1
8.50 (dd, 1H, J1 = 4.7 Hz, J2 = 1.1 Hz), 7.67 (dt, 1H, J1 = 7.9 Hz, J2 =
1.6 Hz), 7.62 (d, 2H, J = 8.2 Hz), 7.38−7.34 (m, 3H), 7.31−7.30 (m,
4H), 7.23 (dd, 1H, J1 = 7.8 Hz, J2 = 5.0 Hz), 2.45 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 152.1, 148.4, 145.4, 138.6, 138.4, 133.0,
129.7, 129.3, 128.6, 128.3, 126.5, 123.1, 120.1, 86.2, 67.5, 21.8; FT-IR
(0.0583 g, white solid); mp 130.1−131.1 °C; H NMR (400 MHz,
CDCl3) δ 7.53 (d, 2H, J = 8.3 Hz), 7.30−7.26 (m, 2H), 7.25−7.20
(m, 5H), 7.20−7.16 (m, 5H), 2.32 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 145.1, 139.0, 133.0, 131.5, 129.6, 129.2, 128.38,
128.36, 128.1, 126.3, 122.7, 83.1, 70.6, 21.8 (one carbon signal is
(KBr) υ 2959, 2926, 2854, 2238, 1594, 1491, 1456, 1376, 1261, 1169,
missing due to the overlapping); FT-IR (KBr) υ 3298, 2961, 2240,
̅
̅
1086, 1022, 801, 686, 654, 583, 562, 544 cm−1; HRMS (ESI+) m/z
calcd for C20H16N2NaO2S+ [M + Na]+ 371.0830 found 371.0835.
4 - M e t h y l - N - p h e n y l - N - ( t h i o p h e n - 3 - y l e t h y n y l ) -
benzenesulfonamide (8ag). (Table 3, entry 6) Prepared from
ynamide 5a (65.1 mg, 0.24 mmol) and 7g (20 μL, 0.2 mmol); silica
gel purification (2 cm × 14 cm, ethyl acetate/petroleum ether = 1:50,
Rf = 0.5 (EtOAc/PE = 1:5)); yield: 69% (0.0491 g, yellowish acicular
solid); mp 132.6−133.8 °C; 1H NMR (500 MHz, CDCl3) δ 7.63 (d,
2H, J = 8.2 Hz), 7.40 (d, 1H, J = 2.8 Hz), 7.33−7.30 (m, 6H), 7.29−
7.25 (m, 2H), 7.08 (d, 1H, J = 4.9 Hz), 2.46 (s, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 145.1, 139.1, 133.3, 130.3, 129.6, 129.2, 129.0,
2130, 2926, 1595, 1490, 1374, 1176, 1090, 813, 691, 583, 549 cm−1;
HRMS (ESI+) m/z calcd for C21H17NNaO2S+ [M + Na]+ 370.0878
found 370.0876.
Methyl-N-phenyl-N-(p-tolylethynyl)benzenesulfonamide (8ab).
(Table 3, entry 1) Prepared from ynamide 5a (65.1 mg, 0.24
mmol) and 7b (0.0436 g, 0.2 mmol); silica gel purification (2 cm ×
14 cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.60 (EtOAc/PE =
1:5)); yield: 65% (0.0473 g, yellowish acicular solid); mp 105.1−
1
106.2 °C; H NMR (500 MHz, CDCl3) δ 7.63 (d, 2H, J = 8.2 Hz),
7.35−7.32 (m, 5H), 7.31−7.29 (m, 4H), 7.12 (d, 2H, J = 7.9 Hz),
2.45 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
145.0, 139.2, 138.3, 133.1, 131.6, 129.6, 129.17, 129.16, 128.4, 128.3,
128.45, 128.37, 126.4, 125.4, 121.5, 82.5, 65.8, 21.9; FT-IR (KBr) υ
̅
126.4, 119.6, 82.4, 70.7, 21.8, 21.6; FT-IR (KBr) υ 2926, 2856, 2239,
2924, 2857, 2237, 1595, 1491, 1370, 1294, 1167, 1088, 866, 782, 690,
̅
E
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Note
657, 584, 565, 542 cm−1; HRMS (ESI+) m/z calcd for
4-Methyl-N-(naphthalen-1-ylethynyl)-N-phenylbenzenesulfona-
mide (8am). (Table 3, entry 12) Prepared from ynamide 5a (65.1
mg, 0.24 mmol) and 7m (29 μL, 0.2 mmol); silica gel purification (2
cm × 14 cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.5 (EtOAc/
PE = 1:5)); yield: 76% (0.061 g, yellowish oil); 1H NMR (500 MHz,
d6-acetone) δ 8.25 (d, 1H, J = 8.1 Hz), 7.96 (d, 1H, J = 8.0 Hz), 7.92
(d, 1H, J = 8.3 Hz), 7.71 (d, 2H, J = 8.2 Hz), 7.65 (d, 1H, J = 7.1 Hz),
7.62 (td, 1H, J1 = 7.0 Hz, J2 = 1.3 Hz), 7.58 (td, 1H, J1 = 6.8 Hz, J2 =
1.2 Hz), 7.50−7.41 (m, 8H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz,
d6-acetone) δ 146.6, 139.9, 134.3, 134.02, 134.00, 133.96, 130.8,
130.6, 130.3, 129.41, 129.37, 129.3, 129.1, 127.8, 127.5, 126.9, 126.6,
+
C19H15NNaO2S2 [M + Na]+ 376.0442 found 376.0439.
4-Methyl-N-phenyl-N-(quinolin-3-ylethynyl)benzenesulfonamide
(8ah). (Table 3, entry 7) Prepared from ynamide 5a (65.1 mg, 0.24
mmol) and 7h (0.052 g, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:15, Rf1 = 0.3 (EtOAc/PE =
1:5)); yield: 86% (0.0683 g, yellowish oil); H NMR (500 MHz,
CDCl3) δ 8.84 (d, 1H, J = 2.1 Hz), 8.16 (d, 1H, J = 1.8 Hz), 8.07 (d,
1H, J = 8.4 Hz), 7.74 (d, 1H, J = 8.2 Hz), 7.69 (td, 1H, J1 = 6.9 Hz, J2
= 1.4 Hz), 7.66 (d, 2H, J = 8.4 Hz), 7.54 (td, 1H, J1 = 7.0 Hz, J2 = 1.0
Hz), 7.40−7.34 (m, 5H), 7.31 (d, 2H, J = 8.1 Hz), 2.44 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 152.0, 146.7, 145.4, 138.7,
126.3, 120.9, 88.6, 69.5, 21.6; FT-IR (KBr) υ 3060, 2926, 2852, 2232,
̅
138.0, 133.0, 130.0, 129.7, 129.4, 129.3, 128.6, 128.4, 127.6, 127.4,
1594, 1489, 1373, 1174, 1122, 1090, 800, 773, 691, 586, 571, 548
cm−1; HRMS (ESI+) m/z calcd for C25H20NO2S+ [M + H]+ 398.1209
found 398.1200.
127.3, 126.4, 117.0, 86.1, 68.2, 21.8; FT-IR (KBr) υ 3065, 2929, 2856,
̅
2235, 1596, 1490, 1376, 1305, 1175, 1163, 1091, 917, 813, 754, 692,
666, 580, 546 cm−1; HRMS (ESI+) m/z calcd for C24H18N2NaO2S+
[M + Na]+ 421.0987 found 421.0989.
N-Benzyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8ba). (Table 4, entry 1) Prepared from ynamide 5b (0.0684 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.6 (EtOAc/PE =
1:5)); yield: 56% (0.040 g, yellowish acicular crystal); mp 122.8−
N-((4-Fluorophenyl)ethynyl)-4-methyl-N-phenylbenzenesulfona-
mide (8ai). (Table 3, entry 8) Prepared from ynamide 5a (65.1 mg,
0.24 mmol) and 7i (23 μL, 0.2 mmol); silica gel purification (2 cm ×
14 cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.61 (EtOAc/PE =
1:5)); yield: 72% (0.0526 g, yellowish acicular solid); mp 82.1−83.0
°C; 1H NMR (500 MHz, d6-acetone) δ 7.66 (dt, 2H, J1 = 8.4 Hz, J2 =
1.8 Hz), 7.50−7.45 (m, 4H), 7.45−7.40 (m, 3H), 7.35−7.33 (m, 2H),
7.15 (tt, 2H, J1 = 8.9 Hz, J2 = 2.2 Hz), 2.45 (s, 3H); 13C{1H} NMR
1
124.0 °C; H NMR (400 MHz, d6-acetone) δ 7.91 (d, 2H, J = 8.3
Hz), 7.48 (d, 2H, J = 7.9 Hz), 7.42−7.38 (m, 2H), 7.38−7.34 (m,
2H), 7.34−7.24 (m, 6H), 4.64 (s, 2H), 2.45 (s, 3H); 13C{1H} NMR
(100 MHz, d6-acetone) δ 145.9, 135.8, 135.6, 131.6, 130.8, 129.7,
129.3, 129.2, 129.1, 128.5, 123.6, 83.8, 71.8, 56.3, 21.5 (one carbon
1
(125 MHz, d6-acetone) δ 163.3 (d, JC−F = 246.2 Hz), 146.5, 139.8,
signal is missing due to the overlapping); FT-IR (KBr) υ 2930, 2856,
̅
3
1699, 1597, 1496, 1455, 1357, 1166, 974, 814, 699, 578, 547 cm−1;
HRMS (ESI+) m/z calcd for C22H20NO2S+ [M + H]+ 362.1209 found
362.1179.
134.5 (d, JC−F = 8.4 Hz), 133.9, 130.7, 130.2, 129.3, 129.1, 126.9,
2
119.6 (d, 4JC−F = 3.4 Hz), 116.5 (d, JC−F = 22 Hz), 83.6, 70.1, 21.5;
FT-IR (KBr) υ 2926, 2855, 2242, 1598, 1508, 1374, 1175, 836, 691,
̅
580 cm−1; HRMS (ESI+) m/z calcd for C21H16FNNaO2S+ [M + Na]+
388.0783 found 388.0782.
N-Butyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (8ca).
(Table 4, entry 2) Prepared from ynamide 5c (0.0603 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.54 (EtOAc/PE =
1:5)); yield: 52% (0.034 g, orange oil); 1H NMR (500 MHz, CDCl3)
δ 7.85 (d, 2H, J = 8.3 Hz), 7.38−7.35 (m, 4H), 7.32−7.27 (m, 3H),
3.41 (t, 2H, J = 7.2 Hz), 2.46 (s, 3H), 1.73−1.67 (m, 2H), 1.43−1.34
(m, 2H), 0.94 (t, 3H, J = 7.4 Hz); 13C{1H} NMR (125 MHz, CDCl3)
δ 144.7, 134.7, 131.4, 129.9, 128.4, 127.83, 127.80, 123.1, 82.6, 70.7,
4-Methyl-N-phenyl-N-((4-(trifluoromethyl)phenyl)ethynyl)-
benzenesulfonamide (8aj). (Table 3, entry 9) Prepared from
ynamide 5a (65.1 mg, 0.24 mmol) and 7j (29 μL, 0.2 mmol); silica
gel purification (2 cm × 14 cm, ethyl acetate/petroleum ether = 1:50,
Rf = 0.61 (EtOAc/PE = 1:5)); yield: 80% (0.0654 g, white prisms);
mp 151.8−152.6 °C; 1H NMR (500 MHz, CDCl3) δ 7.63 (d, 2H, J =
8.2 Hz), 7.56 (d, 2H, J = 8.3 Hz), 7.48 (d, 2H, J = 8.2 Hz), 7.38−7.36
(m, 3H), 7.33−7.30 (m, 4H), 2.45 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 145.4, 138.7, 133.1, 131.3, 129.8, 129.4, 128.8 (q, J =
97 Hz), 128.7, 128.4, 126.8, 126.5, 125.3 (q, J = 3.8 Hz), 124.2 (q, J =
51.5, 30.1, 21.8, 19.6, 13.7; FT-IR (KBr) υ 2960, 2927, 2234, 1598,
̅
1366, 1171, 1091, 756, 691, 676, 583, 547 cm−1; HRMS (ESI+) m/z
calcd for C19H21NNaO2S+ [M + Na]+ 350.1191 found 350.1192.
N-Isopropyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8da). (Table 4, entry 3) Prepared from ynamide 5d (0.0569 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.51 (EtOAc/PE =
1:5)); yield: 96% (0.0601 g, yellowish oil); this ynamide hydrolyzes
quickly in CDCl3 and d6-acetone to afford N-isopropyl-2-phenyl-N-
tosylacetamide; however, it is intact for HRMS; 1H NMR (500 MHz,
CDCl3) δ 7.70 (d, 2H, J = 8.3 Hz), 7.34−7.32 (m, 3H), 7.31−7.27
(m, 2H), 7.16−7.15 (m, 2H), 4.43 (hept, 1H, J = 6.8 Hz), 4.08 (s,
2H), 2.47 (s, 3H), 1.41 (d, 6H, J = 6.9 Hz); 13C{1H} NMR (125
MHz, CDCl3) δ 171.6, 144.8, 137.2, 134.2, 130.0, 129.5, 128.6, 127.5,
270.4 Hz), 85.7, 69.8, 21.8; FT-IR (KBr) υ 2925, 2854, 2237, 1594,
̅
1490, 1376, 1323, 1174, 841, 656, 574 cm−1; HRMS (ESI+) m/z calcd
for C22H16F3NNaO2S+ [M + Na]+ 438.0752 found 438.0756.
4-Methyl-N-((4-nitrophenyl)ethynyl)-N-phenylbenzenesulfona-
mide (8ak). (Table 3, entry 10) Prepared from ynamide 5a (65.1 mg,
0.24 mmol) and 7k (0.0498 g, 0.2 mmol); silica gel purification (2 cm
× 14 cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.61 (EtOAc/PE
= 1:5)); yield: 46% (0.0361 g, yellowish powder); mp 118.9−120.1
°C; 1H NMR (500 MHz, d6-acetone) δ 8.23 (dt, 2H, J1 = 9.0 Hz, J2 =
2.4 Hz), 7.70 (dt, 2H, J1 = 8.4 Hz, J2 = 1.8 Hz), 7.66 (dt, 2H, J1 = 9.0
Hz, J2 = 2.3 Hz), 7.49−7.46 (m, 2H), 7.47−7.44 (m, 3H), 7.37−7.35
(m, 2H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz, d6-acetone) δ
147.6, 146.9, 139.2, 133.8, 132.2, 130.8, 130.6, 130.4, 129.7, 129.1,
127.1, 53.6, 44.7, 21.7, 20.6; FT-IR (KBr) υ 2973, 2929, 1691, 1598,
̅
1496, 1455, 1353, 1164, 1085, 988, 725, 669, 588, 554 cm−1; HRMS
(ESI+) m/z calcd for C18H20NO2S+ [M + H]+ 314.1215 found
314.1235.
127.0, 124.6, 89.3, 70.7, 21.6; FT-IR (KBr) υ 2925, 2854, 1598, 1522,
̅
1488, 1346, 1168, 1087, 854, 694, 562 cm−1; HRMS (ESI+) m/z calcd
for C21H16N2NaO4S+ [M + Na]+ 415.0728 found 415.0732.
(S)-4-Methyl-N-(1-phenylethyl)-N-(phenylethynyl)-
benzenesulfonamide (8ea). (Table 4, entry 4) Prepared from
ynamide 5e (0.0719 g, 0.24 mmol) and PhI (22 μL, 0.2 mmol); silica
gel purification (2 cm × 14 cm, ethyl acetate/petroleum ether = 1:50,
Rf = 0.5 (EtOAc/PE = 1:5)); yield: 89% (0.0667 g, yellowish oil); 1H
NMR (500 MHz, CDCl3) δ 7.58 (d, 2H, J = 8.3 Hz), 7.25−7.19 (m,
7 H), 7.18−7.15 (m, 3H), 7.12 (d, 2H, J = 8.1 Hz), 5.16 (q, 1H, J =
7.1 Hz), 2.31 (s, 3H), 1.51 (d, 3H, J = 7 Hz); 13C{1H} NMR (125
MHz, CDCl3) δ 144.4, 139.9, 135.5, 131.2, 129.9, 129.6, 128.5, 128.4,
4-Methyl-N-((3-nitrophenyl)ethynyl)-N-phenylbenzenesulfona-
mide (8al). (Table 3, entry 11) Prepared from ynamide 5a (65.1 mg,
0.24 mmol) and 7l (0.0498 g, 0.2 mmol); silica gel purification (2 cm
× 14 cm, ethyl acetate/petroleum ether = 1:50, then 1:30, Rf = 0.4
1
(EtOAc/PE = 1:5)); yield: 71% (0.056 g, yellowish oil); H NMR
(500 MHz, CDCl3) δ 8.18 (s, 1H), 8.13−8.11 (m, 1H), 7.69 (d, 1H, J
= 7.7 Hz), 7.63 (d, 2H, J = 8.3 Hz), 7.49 (t, 1H, J = 8 Hz), 7.39−7.37
(m, 3H), 7.34−7.30 (m, 4H), 2.46 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 148.2, 145.6, 138.5, 136.9, 133.0, 129.8, 129.46,
129.43, 128.8, 128.3, 126.5, 125.9, 124.8, 122.6, 85.7, 68.8, 21.8; FT-
128.1, 127.7, 127.0, 123.3, 80.5, 73.4, 59.1, 21.7, 19.8; FT-IR (KBr) υ
̅
IR (KBr) υ 2925, 2854, 2239, 1530, 1351, 1170, 794, 691, 584 cm−1;
3063, 3032, 2978, 2929, 1699, 1597, 1496, 1453, 1356, 1169, 1084,
975, 696, 668, 581, 548 cm−1; HRMS (ESI+) m/z calcd for
C23H21NNaO2S+ [M + Na]+ 398.1191 found 398.1189.
̅
HRMS (ESI+) m/z calcd for C21H16N2NaO4S+ [M + Na]+ 415.0728
found 415.0733.
F
https://dx.doi.org/10.1021/acs.joc.0c02326
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
N-Cyclopropyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8fa). (Table 4, entry 5) Prepared from ynamide 5f (0.056 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:100, Rf = 0.66 (EtOAc/PE =
= 1:5)); yield: 93% (0.100 g, white powder); mp 157.4−158.4 °C; 1H
NMR (500 MHz, d6-acetone) δ 7.90 (d, 2H, J = 8.3 Hz), 7.50 (d, 2H,
J = 8.0 Hz), 7.33−7.31 (m, 3H), 7.28−7.26 (m, 2H), 7.18 (d, 1H, J =
8.2 Hz), 6.97 (dd, 1H, J1 = 8.1 Hz, J2 = 1.5 Hz), 6.81 (s, 1H), 3.42 (d,
1H, J = 13.9 Hz), 3.35 (d, 1H, J = 13.9 Hz), 2.97−2.90 (m, 1H),
2.81−2.76 (m, 2H), 2.45 (s, 3H), 2.35 (d, 1H, J = 11.7 Hz), 1.99 (d,
1H, J = 11.8 Hz), 1.84−1.79 (m, 2H), 1.78−1.75 (m, 2H), 1.73−1.70
(m, 1H), 1.60−1.59 (m, 1H), 1.42−1.33 (m, 1H), 1.22 (s, 3H), 1.18
(dd, J1 = 6.9 Hz, J2 = 0.9 Hz, 6H), 1.06 (s, 3H); 13C{1H} NMR (125
MHz, d6-acetone) δ 148.1, 146.3, 145.9, 135.4, 135.3, 131.8, 130.7,
129.3, 128.8, 128.7, 127.5, 124.8, 124.5, 123.8, 86.8, 70.1, 63.2, 45.2,
39.4, 39.1, 38.2, 37.2, 34.3, 25.8, 24.42, 24.36, 21.5, 19.8, 19.24, 19.21;
1
1:5)); yield: 98% (0.061 g, yellowish oil); H NMR (400 MHz, d6-
acetone) δ 7.92 (d, 2H, J = 8.2 Hz), 7.52 (d, 2H, J = 8.1 Hz), 7.39−
7.33 (m, 5H), 2.90 (quint, 1H, J = 5.1 Hz), 2.47 (s, 3H), 0.83 (d, 4H,
J = 5.3 Hz); 13C{1H} NMR (100 MHz, d6-acetone) δ 146.1, 134.7,
131.9, 130.8, 129.3, 128.9, 128.7, 123.7, 82.9, 71.1, 33.6, 21.6, 6.6; FT-
IR (KBr) υ 2923, 2851, 2234, 1370, 1174, 1091, 862, 814, 755, 672,
̅
573, 548 cm−1; HRMS (ESI+) m/z calcd for C18H17NNaO2S+ [M +
Na]+ 334.0878 found 334.0872.
N-Cyclobutyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8ga). (Table 4, entry 6) Prepared from ynamide 5g (0.0598 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:40, Rf = 0.46 (EtOAc/PE =
1:5)); yield: 74% (0.0507 g, orange oil); 1H NMR (500 MHz,
CDCl3) δ 7.83 (d, 2H, J = 8.3 Hz), 7.43−7.42 (m, 2H), 7.35−7.30
(m, 5H), 4.48 (quint, 1H, J = 7.9 Hz), 2.45 (s, 3H), 2.30−2.21 (m,
2H), 2.11−2.05 (m, 2H), 1.72−1.60 (m, 2H); 13C{1H} NMR (125
MHz, CDCl3) δ 144.7, 135.3, 131.5, 129.8, 128.4, 127.9, 127.7, 123.1,
FT-IR (KBr) υ 2929, 2869, 2235, 1598, 1495, 1367, 1170, 1002, 813,
̅
754, 692, 655, 589, 547; HRMS (ESI+) m/z calcd for
C35H41NNaO2S+ [M + Na]+ 562.2756 found 562.2752.
N-Phenyl-N-(phenylethynyl)methanesulfonamide (8la). (Table
4, entry 11) Prepared from ynamide 5l (0.047 g, 0.24 mmol) and PhI
(22 μL, 0.2 mmol); silica gel purification (2 cm × 14 cm, ethyl
acetate/petroleum ether = 1:50, Rf = 0.61 (EtOAc/PE = 1:5)); yield:
1
84% (0.046 g, orange powder); mp 118.6−119.4 °C; H NMR (400
MHz, d6-acetone) δ 7.66 (d, 2H, J = 7.8 Hz), 7.53−7.48 (m, 4H),
7.44−7.40 (m, 1H), 7.38−7.36 (m, 3H), 3.32 (s, 3H); 13C{1H} NMR
(100 MHz, d6-acetone) δ 139.9, 132.2, 130.3, 129.3, 129.1, 129.0,
80.1, 73.3, 53.8, 28.5, 21.8, 14.6; FT-IR (KBr) υ 2926, 2854, 1703,
̅
1495, 1455, 1356, 1168, 1092, 974, 813, 725, 700, 665, 588, 550
cm−1; HRMS (ESI+) m/z calcd for C19H19NNaO2S+ [M + Na]+
348.1034 found 348.1035.
126.6, 123.3, 83.5, 71.0, 37.4; FT-IR (KBr) υ 2925, 2851, 2240, 1593,
̅
1490, 1366, 1167, 959, 756, 691, 545; HRMS (ESI+) m/z calcd for
C15H14NO2S+ [M + H]+ 272.0745 found 272.0740.
N-Cyclopentyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8ha). (Table 4, entry 7) Prepared from ynamide 5h (0.0631 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:60, Rf = 0.58 (EtOAc/PE =
1:5)); yield: 56% (0.0379 g, orange oil); 1H NMR (500 MHz,
CDCl3) δ 7.86 (d, 2H, J = 8.3 Hz), 7.39−7.37 (m, 2H), 7.35 (d, 2H, J
= 8.0 Hz), 7.32−7.27 (m, 3H), 4.38 (quint, 1H, J = 8.0 Hz), 2.46 (s,
3H), 1.84−1.79 (m, 2H), 1.72−1.63 (m, 4H), 1.53−1.50 (m, 2H);
13C{1H} NMR (125 MHz, CDCl3) δ 144.6, 135.6, 131.3, 129.8,
p-Nitro-N-phenyl-N-(phenylethynyl)benzenesulfonamide (8ma).
(Table 4, entry 12) Prepared from ynamide 5m (0.0725 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.58 (EtOAc/PE =
1:5)); yield: 68% (0.051 g, yellowish prisms); mp 102.9−104.1 °C;
1H NMR (500 MHz, CDCl3) δ 8.36 (dt, 2H, J1 = 9.0 Hz, J2 = 2.0
Hz), 7.93 (dt, 2H, J1 = 9.0 Hz, J2 = 2.3 Hz), 7.41−7.38 (m, 5H),
7.34−7.31 (m, 5H); 13C{1H} NMR (125 MHz, CDCl3) δ 151.0,
141.3, 138.4, 131.8, 129.62, 129.61, 129.0, 128.69, 128.58, 126.3,
128.4, 127.8, 127.7, 123.2, 80.4, 72.8, 61.2, 30.4, 24.4, 21.8; FT-IR
(KBr) υ 2925, 2855, 2130, 1596, 1489, 1374, 1174, 1091, 813, 761,
124.3, 122.0, 81.8, 71.3; FT-IR (KBr) υ 3104, 2924, 2852, 2241,
̅
̅
691, 657, 584, 548 cm−1; HRMS (ESI+) m/z calcd for
1592, 1533, 1490, 1382, 1348, 1181, 1088, 925, 855, 784, 738, 691,
607, 576, 558 cm−1; HRMS (ESI+) m/z calcd for C20H14N2NaO4S+
[M + Na]+ 401.0572 found 401.0578.
C20H21NNaO2S+ [M + Na]+ 362.1191 found 362.1193.
N-Cyclohexyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8ia). (Table 4, entry 8) Prepared from ynamide 5i (0.067 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:100, Rf = 0.71 (EtOAc/PE =
1:5)); yield: 64% (0.045 g, orange oil); 1H NMR (500 MHz, CDCl3)
δ 7.86 (d, 2H, J = 8.4 Hz), 7.39 (dd, 2H, J1 = 8.1 Hz, J2 = 1.8 Hz),
7.35−7.30 (m, 4H), 7.29−7.27 (m, 1H), 3.86 (tt, 1H, J1 = 11.8 Hz, J2
= 4.1 Hz), 2.45 (s, 3H), 1.79−1.76 (m, 2H), 1.73−1.71 (m, 2H),
1.63−1.59 (m, 1H), 1.53 (td, 2H, J1 = 12.3 Hz, J2 = 3.6 Hz), 1.37−
1.30 (m, 2H), 1.20−1.08 (m, 1H); 13C{1H} NMR (125 MHz,
CDCl3) δ 144.5, 136.4, 131.4, 129.8, 128.4, 127.7, 127.5, 123.4, 80.4,
1-(Phenylethynyl)-1H-indole (8na). (Table 4, entry 13) Prepared
from ynamide 5n (0.0339 g, 0.24 mmol) and PhI (22 μL, 0.2 mmol);
silica gel purification (2 cm × 14 cm, petroleum ether, Rf = 0.80
(PE)); yield: 65% (0.0282 g, yellowish powder); mp 56.8−58.1 °C;
prepared from ynamide 5n (1 g, 7.08 mmol) and PhI (1 mL, 9.2
mmol), yield: 41% (0.63 g); 1H NMR (500 MHz, CDCl3) δ 7.70 (d,
1H, J = 8.2 Hz), 7.67 (d, 1H, J = 8.0 Hz), 7.61 (d, 2H, J = 7.4 Hz),
7.44−7.38 (m, 4H), 7.32 (d, 1H, J = 3.3 Hz), 7.28 (t, 1H, J = 7.6 Hz),
6.65 (d, 1H, J = 3.3 Hz); 13C{1H} NMR (125 MHz, CDCl3) δ 138.2,
131.5, 128.9, 128.6, 128.1, 128.0, 123.7, 122.7, 122.1, 121.3, 111.4,
72.5, 59.7, 31.3, 25.5, 25.0, 21.8; FT-IR (KBr) υ 2932, 2854, 1590,
105.7, 80.9, 70.7; FT-IR (KBr) υ 2924, 2241, 1522, 1459, 1348, 1204,
̅
̅
1454, 1359, 1169, 1090, 996, 813, 667, 591, 550 cm−1; HRMS (ESI+)
m/z calcd for C21H24NO2S+ [M + H]+ 354.1528 found 354.1537.
N-Cycloheptyl-4-methyl-N-(phenylethynyl)benzenesulfonamide
(8ja). (Table 4, entry 9) Prepared from ynamide 5j (0.0696 g, 0.24
mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm × 14
cm, ethyl acetate/petroleum ether = 1:50, Rf = 0.54 (EtOAc/PE =
1:5)); yield: 86% (0.063 g, orange oil); 1H NMR (500 MHz, CDCl3)
δ 7.87 (d, 2H, J = 8.3 Hz), 7.40 (dd, 2H, J1 = 8.0 Hz, J2 = 1.6 Hz),
7.36 (d, 2H, J = 8.1 Hz), 7.34−7.29 (m, 3H), 4.06 (hept, 1H, J = 4.9
Hz), 2.47 (s, 3H), 1.86−1.75 (m, 4H), 1.73−1.67 (m, 2H), 1.62−
1.56 (m, 2H), 1.47−1.41 (m, 2H), 1.54−1.49 (m, 2H); 13C{1H}
NMR (125 MHz, CDCl3) δ 144.4, 136.1, 131.3, 129.8, 128.3, 127.62,
1164, 742, 690 cm−1; HRMS (ESI+) m/z calcd for C16H12N+ [M +
H]+ 218.0970 found 218.0968.
9-(Phenylethynyl)-9H-carbazole (8oa). (Table 4, entry 14)
Prepared from ynamide 5o (0.0459 g, 0.24 mmol) and PhI (22 μL,
0.2 mmol); silica gel purification (2 cm × 14 cm, ethyl acetate/
petroleum ether = 1:80, Rf = 0.53 (EtOAc/PE = 1:10)); yield: 50%
(0.0267 g, white powder); mp 108.7−110.0 °C; 1H NMR (400 MHz,
CDCl3) δ 8.07 (d, 2H, J = 7.7 Hz), 7.77 (d, 2H, J = 8.1 Hz), 7.67 (d,
2H, J = 6.7 Hz), 7.57 (t, 2H, J = 8 Hz), 7.46−7.37 (m, 5H); 13C{1H}
NMR (100 MHz, CDCl3) δ 140.6, 131.5, 128.6, 128.1, 126.9, 123.7,
123.1, 122.2, 120.5, 111.4, 79.0, 74.7; FT-IR (KBr) υ 3052, 2922,
̅
2247, 1480, 1452, 1224, 747, 720, 689, 563 cm−1; HRMS (ESI+) m/z
calcd for C20H14N+ [M + H]+ 268.1126 found 268.1134.
127.56, 123.4, 80.8, 72.3, 61.9, 33.7, 28.1, 24.4, 21.8; FT-IR (KBr) υ
̅
2926, 2856, 2234, 1693, 1598, 1495, 1455, 1362, 1167, 1090, 971,
813, 705, 666, 591, 550 cm−1; HRMS (ESI+) m/z calcd for
C22H25NNaO2S+ [M + Na]+ 390.1504 found 390.1501.
Procedure to Synthesize 4-Methyl-N-(pent-4-en-1-yn-1-yl)-N-
phenylbenzenesulfonamide (9a). To a solution of ynamide 5a
(0.135 mg, 0.5 mmol), allyl chloride (0.163 mL, 2 mmol), and
cetrimonium bromide (2 g) in water (4 mL) was charged CuI (9.5
mg), dppp (20.6 mg), and K2CO3 (0.138 g) under nitrogen
protection. After being stirred at room temperature under nitrogen
protection for 3 h, the reaction mixture was extracted with EtOAc (3
N-Phenylacetylenyl-N-dehydroabietyl-4-methylbenzenesulfona-
mide (8ka). (Table 4, entry 10) Prepared from ynamide 5k (0.111 g,
0.24 mmol) and PhI (22 μL, 0.2 mmol); silica gel purification (2 cm
× 14 cm, ethyl acetate/petroleum ether = 1:70, Rf = 0.63 (EtOAc/PE
G
https://dx.doi.org/10.1021/acs.joc.0c02326
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
× 20 mL). The combined organic layer was washed with brine, dried
over MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (2 cm × 14 cm, ethyl acetate/
petroleum ether = 1:40, Rf = 0.58 (EtOAc/PE = 1:5)) to afford 9a as
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
1
■
colorless oil; yield: 99% (0.154 g); H NMR (400 MHz, CDCl3) δ
7.48 (d, 2H, J1 = 8.4 Hz, J2 = 1.7 Hz), 7.24−7.20 (m, 2H), 7.19−7.17
(m, 5H), 5.73 (dquint, 1H, J1 = 17.0 Hz, J2 = 5.1 Hz), 5.21 (dq, 1H, J1
= 17.0 Hz, J2 = 1.8 Hz), 5.02 (dq, 1H, J1 = 10.0 Hz, J2 = 1.7 Hz), 3.01
(dt, 2H, J1 = 5.1 Hz, J2 = 1.8 Hz), 2.35 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.9, 139.3, 133.1, 132.6, 129.5, 129.1, 128.4, 128.1,
Na Wu − School of Chemistry and Bioscience, University of
Bradford, Bradford, West Yorkshire BD7 1DP, U.K.;
orcid.org/0000-0003-1668-6652; Email: n.wu1@
bradford.ac.uk
126.3, 116.2, 76.3, 66.9, 22.9, 21.8; FT-IR (KBr) υ 2925, 2854, 1708,
̅
1596, 1490, 1361, 1165, 1088, 922, 813, 756, 696, 569; HRMS (ESI+)
m/z calcd for C18H18NO2S+ [M + H]+ 312.1058 found 312.1060.
Hydroacyloxylation of Ynamide in Water to Synthesize 1-(4-
Methyl-N-phenylphenylsulfonamido)vinyl Benzoate (10a). To a 10
mL round-bottom flask was charged ynamide 5a (0.054 g, 0.2 mmol),
benzoic acid (0.0268 g, 0.22 mmol), and cetrimonium bromide (2 g)
in water (4 mL). The reaction was stirred at 60 °C using a heating
mantle for 3 h. Then, the reaction mixture was extracted with EtOAc
(3 × 20 mL). The combined organic layer was washed with brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (2 cm × 14 cm, ethyl
acetate/petroleum ether = 1:40, Rf = 0.38 (EtOAc/PE = 1:5)) to
afford 10a as yellowish oil; yield: 92% (0.072 g); 1H NMR (400 MHz,
CDCl3) δ 7.76 (d, 2H, J = 8.4 Hz), 7.56 (d, 2H, J = 8.3 Hz), 7.49 (tt,
1H, J1 = 7.4 Hz, J2 = 1.2 Hz), 7.31 (t, 2H, J = 8 Hz), 7.25−7.23 (m,
5H), 7.09 (d, 2H, J = 8.1 Hz), 5.02 (dt, 2H, J1 = 2.7 Hz, J2 = 1.8 Hz),
2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.4, 145.7,
144.1, 138.7, 136.7, 133.8, 130.1, 129.5, 129.4, 129.0, 128.7, 128.5,
128.1, 101.9, 21.6 (one carbon signal is missing due to the
Authors
Lei Zhao − State Key Laboratory for the Chemistry and
Molecular Engineering of Medicinal Resources, School of
Chemistry and Pharmaceutical Science, Guangxi Normal
University, Guilin, Guangxi 541004, China
Hongyi Yang − State Key Laboratory for the Chemistry and
Molecular Engineering of Medicinal Resources, School of
Chemistry and Pharmaceutical Science, Guangxi Normal
University, Guilin, Guangxi 541004, China
Ruikun Li − State Key Laboratory for the Chemistry and
Molecular Engineering of Medicinal Resources, School of
Chemistry and Pharmaceutical Science, Guangxi Normal
University, Guilin, Guangxi 541004, China
Ye Tao − State Key Laboratory for the Chemistry and
Molecular Engineering of Medicinal Resources, School of
Chemistry and Pharmaceutical Science, Guangxi Normal
University, Guilin, Guangxi 541004, China
overlapping); FT-IR (KBr) υ 2929, 1709, 1596, 1491, 1363, 1164,
Xiao-Feng Guo − College of Biomedical Engineering, Taiyuan
University of Technology, Taiyuan, Shanxi 030024, China
Edward A. Anderson − Chemistry Research Laboratory,
University of Oxford, Oxford OX1 3TA, U.K.; orcid.org/
0000-0002-4149-0494
Andrew Whiting − Department of Chemistry, Durham
University, Durham DH1 3LE, U.K.; orcid.org/0000-
0001-8937-8445
̅
812, 654, 693, 564 cm−1; HRMS (ESI−) m/z calcd for C22H18NO4S−
[M − H]− 392.0957 found 392.0956.
Hydrodithiophosphonylation of Ynamide in Water to Synthe-
size 1-(4-Methyl-N-phenylphenylsulfonamido)vinyl Diphenylphos-
phinodithioate (11a). To a 10 mL round-bottom flask was charged
ynamide 5a (0.054 g, 0.2 mmol), diphenylphosphinodithioic acid
(0.0601 g, 0.24 mmol), and cetrimonium bromide (2 g) in water (4
mL). The reaction was stirred at room temperature for 12 h. Then,
the reaction mixture was extracted with EtOAc (3 × 20 mL). The
combined organic layer was washed with brine, dried over MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (2 cm × 14 cm, ethyl acetate/petroleum
ether = 1:40, Rf = 0.49 (EtOAc/PE = 1:5)) to afford 11a as white
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02326
Notes
1
The authors declare no competing financial interest.
powder; mp 116.1−117.2 °C; yield: 66% (0.069 g); H NMR (400
MHz, CDCl3) δ 7.69 (dd, 2H, J1 = 7.1 Hz, J2 = 1.4 Hz), 7.65 (dd, 2H,
J1 = 7.1 Hz, J2 = 1.4 Hz), 7.48 (d, 2H, J = 8.3 Hz), 7.40−7.36 (m,
2H), 7.30−7.26 (m, 4H), 7.18−7.09 (m, 5H), 7.01−6.98 (m, 2H),
5.75 (t, 1H, J = 1.7 Hz), 5.58 (t, 1H, J = 1.7 Hz), 2.33 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 144.1, 137.3 (J = 93.6 Hz),
135.7 (J = 6.3 Hz), 133.3 (J = 84.6 Hz), 132.0 (J = 3.2 Hz), 131.8 (J =
11.1 Hz), 129.7, 129.2, 129.0, 128.7, 128.6, 128.4, 128.2, 125.4 (J =
ACKNOWLEDGMENTS
■
This work was supported by Royal Society - Newton
International Fellowship (170322), National Natural Science
Foundation of China (21462004), and the State Key
Laboratory for the Chemistry and Molecular Engineering of
Medicinal Resources at Guangxi Normal University
(CMEMR2014-A04).
5.6 Hz), 21.7; FT-IR (KBr) υ 2926, 1709, 1438, 1366, 1165, 812, 694,
̅
+
655, 563 cm−1; HRMS (ESI+) m/z calcd for C27H25NO2PS3 [M +
H]+ 522.0785 found 522.0740.
REFERENCES
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ASSOCIATED CONTENT
(1) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: Oxford, U.K., 1998.
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* Supporting Information
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and Professional: 1998. (b) Li, C. J.; Chan, T. H. Organic Reaction in
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02326.
1H and 13C NMR spectra for compounds 5, 8, 9a, 10a,
and 11a (PDF)
Accession Codes
CCDC 1890688 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
H
https://dx.doi.org/10.1021/acs.joc.0c02326
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
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