First Long-Distance SRN1 on a propargylic chloride

Article abstract of DOI:10.1016/j.tetlet.2012.05.150

We report here the first example of a Long-Distance S_RN1 (LD-S_RN1) reaction on a propargylic chloride. The reaction of 1-(3-chloroprop-1-ynyl)-4-nitrobenzene (1) with nitronate anions led to both the formation of the C-alkylation product through an LD-S_RN1 mechanism and the ethylenic compound resulting from nitrous acid elimination on the C-alkylation product 2. In contrast with previous work on LD-S_RN1 reactivity, no O-alkylation product was observed. Only one original product 4 was isolated under phase transfer conditions, resulting from a nucleophilic attack by 2-nitropropane anion on the electrophilic alkyne. This LD-S _RN1 reactivity did not extend to sulfinate anions; the reaction of 1 with sulfinate anions yielded original ethylenic disulfone compounds which were formed via an ionic process.

Full text of DOI:10.1016/j.tetlet.2012.05.150

Tetrahedron Letters 53 (2012) 4184–4187
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
First Long-Distance SRN1 on a propargylic chloride
⇑
Manon Roche, Thierry Terme, Patrice Vanelle
Aix-Marseille Univ, CNRS, Institut de Chimie Radicalaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie,
27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here the first example of a Long-Distance SRN1 (LD-SRN1) reaction on a propargylic chloride.
The reaction of 1-(3-chloroprop-1-ynyl)-4-nitrobenzene (1) with nitronate anions led to both the forma-
tion of the C-alkylation product through an LD-SRN1 mechanism and the ethylenic compound resulting
from nitrous acid elimination on the C-alkylation product 2. In contrast with previous work on LD-
SRN1 reactivity, no O-alkylation product was observed. Only one original product 4 was isolated under
phase transfer conditions, resulting from a nucleophilic attack by 2-nitropropane anion on the electro-
philic alkyne. This LD-SRN1 reactivity did not extend to sulfinate anions; the reaction of 1 with sulfinate
anions yielded original ethylenic disulfone compounds which were formed via an ionic process.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 11 April 2012
Revised 24 May 2012
Accepted 30 May 2012
Available online 8 June 2012
Keywords:
Single-electron transfer
LD-SRN
1
Propargylic chloride
The concept of Long-Distance Radical Nucleophilic Substitution
(LD-SRN1) involves long distance between the electron
withdrawing and the leaving group.1 LD-SRN1 reactions were
explored by Barker and Norris with a reaction between -alkyl-
(p-nitrophenyl) alkyl chloride2 and various nucleophiles. This
coupling reaction, a mixture of tetrahydrofuran and water
a
(90/10) was used as the solvent. The second step was a classic chlo-
rination of the alcohol with SOCl2 in dichloromethane to obtain 1
in 95% yield.8
a
c
Treated under various electron transfer conditions9,10 with 2-
nitropropane anion, the 1-(3-chloroprop-1-ynyl)-4-nitrobenzene
(1) led to the formation of three compounds: the expected C-alkyl-
ation product 2, the ethylenic compound 3 resulting from nitrous
concept was further explored in heterocyclic3 and in quinonic ser-
ies.4 All this previous research concluded that LD-SRN1 reactivity is
often in competition with another reactivity, usually SN2. For
example, the Barker and Norris substrate reacted with 2-nitropro-
pane anion via an SN2 pathway.2 Moreover, in heterocyclic series,
(E)-2-[4-(chloromethyl)styryl]-1-methyl-5-nitro-1H-imidazole under
LD-SRN1 conditions gave a majority of O-alkylation products.3a
Under our program directed toward the single electron transfer
(SET) reaction,1,5 we considered the possibility that a propargylic
chloride might be reactive under LD-SRN1 conditions with various
nucleophiles. Never previously reported, LD-SRN1 on alkynes would
be invaluable in the preparation of original substrates. Alkyne moi-
eties have elicited great interest in connection with many reactions,
such as ‘click’ chemistry reactions, metal-catalysis, or polymeriza-
tion reactions.6
OH
Cl
Br
Pd(PPh3)4 0,5 %
CuI 1 %
OH
SOCl2
+
CH2Cl2
1) 0°C
pyrolidine
H2O/ THF
NO2
2) 40°C
NO2
85 %
NO2
95 %
1
Scheme 1. Synthesis of propargylic chloride 1.
Continuing in the vein of this study on SRN1 (LD-SRN1) reactivity,
we explored this concept in alkyne series, reporting here the
reaction between nitronate and sulfinate anions under SRN1 exper-
imental conditions (LD-SRN1). We synthesized the 1-(3-chloroprop-
CH3
NO2
CH3
CH3
Cl
O2N
H3C
CH3
Cl
CH3
H
1-ynyl)-4-nitrobenzene 1, using
a Sonogashira cross-coupling
H3C
H3C
hν N2
reaction (Scheme 1).
+
NO2
+
+
For the first step, our synthesis was inspired by the work of
Solvent
Chinchilla7 on Sonogashira reactions. To optimize the rate of
M
NO2
NO2
NO2
NO2
4
2
3
⇑
Corresponding author. Tel.: +33 49183 5580.
E-mail address: patrice.vanelle@univ-amu.fr (P. Vanelle).
Scheme 2. Reactivity of propargylic chloride 1 with the 2-nitropropane anion
under SRN1 conditions.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.150

M. Roche et al. / Tetrahedron Letters 53 (2012) 4184–4187
4185
Table 1
Reactivity of 1 with 2-nitropropane anion
Entrya
M
Equiv of anion
Solvent
Time
Yield 211 (%)
Yield 311 (%)
Yield 411 (%)
Yield C-alkylation (%)
1
2
3
4
5
Li
Li
Li
Li
3
3
3
3
3
3
3
3
2
4
6
DMSO
DMSO
DMSO
DMSO
DMF
DMSO
CH2Cl2/H2O
CH2Cl2/H2O
DMSO
1 min
5 min
25 min
1 h
36 h
25 min
48 h
75
40
32
15
25
65
20
20
42
40
35
10
50
68
77
25
30
—
—
—
—
—
25
—
30
30
—
85
90
100
92
50
95
20
20
97
98
95
Li
6b
7c
8d
9
Na
NBu4
NBu4
Li
Li
Li
48 h
—
25 min
25 min
25 min
55
58
60
10
11
DMSO
DMSO
—
—
a
All reactions were performed under nitrogen and irradiation with a 300 W fluorescent lamp using 1 equiv of 1. All yields refer to chromatographically isolated pure
products and are relative to the electrophile.
b
2-Nitropropane salt was formed in situ using NaH in DMSO and 2-nitropropane.
Phase transfer conditions with NBu4Br in water.
Phase transfer conditions with NBu4OH 40% in water.
c
d
acid elimination on the C-alkylation product 2, and an original allyl
chloride 4 (Scheme 2, Table 1).11 The best overall yield (100%) of C-
alkylation products 2 + 3 was obtained under Kornblum condi-
tions9 with DMSO as the solvent with 3 equiv of 2-nitropropane
anion for 25 min under inert atmosphere and light catalysis (Entry
3). We note that the ethylenic compound 3 was predominant (68%
vs 32%). When we used NaH in DMSO and 2-nitropropane to form
the 2-nitropropane salt in situ (Entry 6), we obtained the C-alkyl-
ation products in 95% overall yield after 25 min. Under these
conditions, the ratio between compounds 2 and 3 is in favor of
C-alkylation product 2 (65% vs 30%).
Moreover, an original product 4 was isolated. High resolution Mass
Spectrometry ESI-MS and RMN NOESY permitted us to determine
Cl
O
O
S
Na
O
H
S
hν N2
O
O
S
+
DMSO
O
NO2
3 equiv
11 45 %
NO2
Under Norris conditions,10 phase transfer reaction conditions
(Entries 7 and 8), we observed the starting chloride 1 with or with-
out degradation products and only 20% of C-alkylation product 2.
Scheme 4. Reaction of
1
with benzenesulfinic acid sodium salt under SRN1
conditions.
R
Table 2
Cl
Inhibition of reaction of 1 with the 2-nitropropane anion
O
Entrya
Scavenger
Yield (2) (%)
Yield (3) (%)
Yield (4) (%)
O
Na
O
H
S
O
O
S
S
3
—
32
0
0
10
5
68
0
0
15
10
0
+
R
DMSO
12
13
14
15
TEMPO 1 Equiv
TEMPO 0,1 Equiv
CuCl2 1 Equiv
CuCl2 0,1 Equiv
62
41
28
15
O
R
11 R = H
12 R = CH3 83 %
13 R = Cl 69 %
75 %
NO2
6 equiv
NO2
a
All reactions were performed under Entry 3 conditions.
Scheme 5. Reaction of 1 with other benzenesulfinic acid sodium salts.
O2N
72 %
5 %
+
NO2
7
8
NO2
O2N
O2N
NO2
+
+
Cl
NO2
47 %
5
NO2
40 %
6
NO2
80 %
NO2
traces
NO2
NO2
10
9
NO2
Scheme 3. Reaction of 1 with nitrocycloalkanes.

4186
M. Roche et al. / Tetrahedron Letters 53 (2012) 4184–4187
R
O
O
S
Na
S
O
O
SN2
R
R
Cl
NO2
O
H
S
O
O
S
Na
O
S
R
O
+
O
R
O
S
Na
NO2
NO2
CH2
C
O
O
R
SN2'
S
O
NO2
R
Scheme 6. Mechanism for the formation of 11–13.
the structure of 4 as (Z)-1-(2-(chloromethyl)-3-methyl-3-nitrobut-
1-enyl)-4-nitrobenzene.
In order to extend this propargyl chloride reactivity to sulfinate
anions, we used other sulfinate anions such as p-toluenesulfinic
and p-chlorobenzene sulfinic acid sodium salt (Scheme 5) in the
reaction with 1 under optimized conditions (non radical). We ob-
served the formation of new compounds 12 and 13 in respectively
83% and 69% yields.13
The formation of these ethylenic disulfone derivatives 11–13
may be explained by two pathways (Scheme 6). The first step could
be an SN2 or an SN20 reaction forming respectively an alkyne sul-
fone or an allene sulfone intermediate. This step could be followed
by a nucleophilic addition of sulfinate anion on the intermediate to
form 11–13. However, the absence of isolated intermediates or by-
products in this reaction makes it impossible to describe this
mechanism clearly.
In conclusion, what we have described here is the first example
of an LD-SRN1 reaction on a propargylic chloride. The reaction of 1-
(3-chloroprop-1-ynyl)-4-nitrobenzene (1) with nitronate anions
led to both the formation of the C-alkylation product through an
LD-SRN1 mechanism and the ethylenic compound resulting from
nitrous acid elimination on the C-alkylation product 2. In contrast
with previous work on LD-SRN1 reactivity, no O-alkylation product
was observed. Only original product 4 was isolated under phase
transfer conditions, resulting from a nucleophilic attack of 2-nitro-
propane anion on the electrophilic alkyne. This LD-SRN1 reactivity
did not extend to sulfinate anions, the reaction of 1 with sulfinate
anions yielded original ethylenic disulfone compounds which were
formed via an ionic process. Pharmacological evaluation of all
these synthesized compounds is in progress, particularly regarding
the original ethylenic disulfone compounds, which are known to
have anticancer potential.14
The reaction of 1 with the 2-nitropropane anion, under the opti-
mal conditions, in the presence of classic inhibitors (2,2,6,6-tetra-
methyl-1-piperidinyloxy or TEMPO as the radical trap and CuCl2)
gave effective inhibition, indicating an LD-SRN1 mechanism for
the formation of 2 (Table 2).
The formation of compounds 2 and 3 is explained by the LD-
SRN1 process leading to C-alkylation product 2. From product 2,
in the presence of an excess of the anion, nitrous acid elimination
gives ethylenic compound 3. However, inhibitions were accompa-
nied by the formation of compound 4. The formation of this prod-
uct seems to be due to an ionic process and was the result of a
nucleophilic addition of the 2-nitropropane anion on the electro-
philic alkyne conjugated with p-nitrobenzene moiety.
In order to generalize this concept, we extended this reaction to
other nucleophiles such as nitrocycloalkanes and synthesized the
corresponding C-alkylation products 5, 7, 9 and the ethylenic prod-
ucts 6, 8, 1012 as shown in Scheme 3. All nitroalkanes were com-
mercially available and their conversion to anions was realized
in situ with NaH in DMSO. All the reactions were performed using
3 equiv of nitrocycloalkane, in DMSO at rt, for 25 min (Table 1, En-
try 6 conditions).
The possible extension of this LD-SRN1 reactivity to S-centered
anions3b was investigated using the benzenesulfinic acid anion.
However, this reaction did not yield the expected S-alkylation
product; instead, an original ethylenic disulfone compound 11
was observed, accompanied by intractable tarry matter. High reso-
lution Mass Spectrometry ESI-MS and NOESY studies permitted us
to determine the structure of 11 as (E)-1-(1,3-bis(phenylsulfo-
nyl)prop-1-enyl)-4-nitrobenzene.
After optimization under SRN1 reaction conditions, the best
yield of 11 (45%) was obtained with 3 equiv of sulfinate anion in
DMSO, stirred at rt for 5 h (Scheme 4). An inhibition reaction with
1 equiv of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) under
the optimal conditions led to the same product with an equivalent
yield (45%). The inhibition experiments showed that the formation
of product 11 was not sensitive to the presence of classic inhibitors
of SRN1 reactions. The formation of this compound was not a radi-
Acknowledgments
This work was supported by the Centre National de la Recher-
che Scientifique. We express our thanks to Vincent Remusat for
1H and 13C NMR spectra recording.
References and notes
1. For a review see: Terme, T.; Crozet, M. P.; Maldonado, J.; Vanelle, P. In Electron
Transfer Reactions in Organic Synthesis; Vanelle, P., Ed.; Research Signpost:
Trivandrum, 2002; pp 1–42.
2. (a) Barker, S. D.; Norris, R. K. Tetrahedron Lett. 1979, 11, 973–974; (b) Barker, S.
D.; Norris, R. K. Aust. J. Chem. 1983, 36, 527–544.
3. (a) Benakli, K.; Kaafarani, M.; Crozet, M. P.; Vanelle, P. Heterocycles 1999, 51,
557–565; (b) Benakli, K.; Terme, T.; Vanelle, P. Molecules 2002, 7, 382–385; (c)
Benakli, K.; Terme, T.; Maldonado, J.; Vanelle, P. Heterocycles 2002, 57, 1689–
cal process. Thus, the LD-SRN1 conditions (inert atmosphere and h
m
irradiation) were not required to form 11. We therefore investi-
gated a possible reaction of nitrobenzyl propargylic chloride 1 with
6 equiv of benzenesulfinic acid sodium salt under non-radical
conditions (air and no light irradiation). Under these conditions,
product 11 was obtained in 75% yield.

M. Roche et al. / Tetrahedron Letters 53 (2012) 4184–4187
4187
1695; (d) Zink, L.; Crozet, M. D.; Terme, T.; Vanelle, P. Tetrahedron Lett. 2011, 52,
6991–6996.
4. Crozet, M. P.; Sabuco, J.-F.; Tamburlin, I.; Barreau, M.; Giraud, L.; Vanelle, P.
Heterocycles 1993, 36, 45–54.
2H); 3.01 (s, 2H); 7.51 (d, J = 8.9 Hz, 2H); 8.15 (d, J = 8.9 Hz, 2H). 13C NMR
(50 MHz, CDCl3) d 24.1 (2xCH2); 24.7 (CH2); 30.9 (2xCH2); 36.2 (CH2); 89.8 (C);
93.2 (C); 96.2 (C); 123.5 (2xCH); 131.1 (C); 131.8 (2xCH); 146.4 (C). Anal Calcd
for C15H16N2O4: C, 62.49; H, 5.59; N, 9.72. Found: C, 62.34; H, 5.77; N, 9.65.
Compound 6: yellow oil, 1H NMR (200 MHz, CDCl3) d 2.24 (m, 8H); 3.70 (m,
2H); 5.45 (s, 1H); 7.53 (d, J = 8.9 Hz, 2H); 8.15 (d, J = 8.9 Hz, 2H). 13C NMR
(50 MHz, CDCl3) d 26.1 (CH2); 27.6 (CH2); 28.2 (CH2); 29.8 (CH2); 32.0 (CH2);
89.8 (C); 93.2 (C); 101.1 (CH); 123.5 (2xCH); 128.6 (C); 131.8 (2xCH); 146.4 (C);
159.4 (C). HRMS Calcd for C15H15NO2 [M+Na+]: 264.0995, Found: 264.0992.
Compound 7: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.63 (m, 8H); 2.02 (m,
2H), 2.54 (m, 2H); 3.06 (s, 2H); 7.51 (d, J = 8.9 Hz, 2H); 8.16 (d, J = 8.9 Hz, 2H).
13C NMR (50 MHz, CDCl3) d 23.2 (2xCH2); 29.8 (2xCH2); 32.2 (CH2); 37.2
(2xCH2); 89.2 (C); 94.4 (C); 100.8 (C); 123.5 (2xCH); 129.7 (C); 132.5 (2xCH);
147.1 (C). Anal Calcd for C16H18N2O4: C, 63.56; H, 6.00; N, 9.27. Found: C, 64.05;
H, 6.30; N, 9.18. Compound 8: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.57 (m,
8H); 2.61 (m, 4H); 5.52 (s, 1H); 7.52 (d, J = 8.9 Hz, 2H); 8.17 (d, J = 8.9 Hz, 2H).
Compound 9: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.70 (s, 8H); 3.15 (s, 2H);
7.47 (d, J = 8.9 Hz, 2H); 8.17 (d, J = 8.9 Hz, 2H). 13C NMR (50 MHz, CDCl3) d 25.0
(2xCH2), 30.1 (CH2), 37.4 (2xCH2), 81.8 (C), 89.4 (C), 97.2 (C), 123.6 (2xCH),
129,7 (C), 132,5 (2xCH), 147,1 (C). HRMS Calcd for C14H14N2O4 [M+Na+]:
297.0845, Found: 297.0846.
5. (a) Khoumeri, O.; Giuglio-Tonolo, G.; Crozet, M. D.; Terme, T. M.; Vanelle, P.
Tetrahedron 2011, 67, 6173–6180; (b) Juspin, T.; Giuglio-Tonolo, G.; Terme, T.;
Vanelle, P. Synthesis 2010, 844–848; (c) Montana, M.; Crozet, M. D.; Castera-
Ducros, C.; Terme, T.; Vanelle, P. Heterocycles 2008, 75, 925–932; (d) Gellis, A.;
Vanelle, P.; Kaafarani, M.; Benakli, K.; Crozet, M. P. Tetrahedron 1997, 53, 5471–
5484; (e) Crozet, M. P.; Gellis, A.; Pasquier, C.; Vanelle, P.; Aune, J. P. Tetrahedron
Lett. 1995, 36, 525–528; (f) Roubaud, C.; Vanelle, P.; Maldonado, J.; Crozet, M. P.
Tetrahedron 1995, 51, 9643–9656; (g) Crozet, M. P.; Giraud, L.; Sabuco, J. F.;
Vanelle, P.; Barreau, M. Tetrahedron Lett. 1991, 32, 4125–4128; (h) Vanelle, P.;
Maldonado, J.; Madadi, N.; Gueiffier, A.; Chapat, J.-P.; Crozet, M. P. Tetrahedron
Lett. 1990, 31, 3013–3016; (i) Crozet, M. P.; Archaimbault, G.; Vanelle, P.;
Nouguier, R. Tetrahedron Lett. 1985, 26, 5133–5134.
6. (a) Iha, R. K.; Wooley, K. L.; Nystrom, A. M.; Burke, D. J.; Kade, M. J.; Hawker, C. J.
Chem. Rev. 2009, 109, 5620–5686; (b) Diez-Gonzalez, S. Curr. Org. Chem. 2011,
15, 2830–2845; (c) He, H.; Gao, C. Curr. Org. Chem. 2011, 15, 3667–3691; (d) Li,
H.-K.; Sun, J.-Z.; Qin, A.-J.; Tang, B. Z. Chin. J. Polym. Sci. 2012, 30, 1–15.
7. Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874–922.
8. Compound 1: Brown solid, mp 58.3 °C, 1H NMR (200 MHz, CDCl3) d 4.37 (s, 2H);
7.56 (d, J = 8.9 Hz, 2H); 8.16 (d, J = 8.9 Hz, 2H). 13C NMR (50 MHz, CDCl3) d 30.4
(CH2); 84.1 (C); 88.9 (C); 123.6 (2xCH); 128.9 (C); 132.7 (2xCH); 147.5 (C). Anal
Calcd for C9H6ClNO2: C, 55.26; H, 3.09; N, 7.16. Found: C, 55.37; H, 3.18; N,
7.19.
13. Purified by alumina gel chromatography with CH2Cl2/petroleum ether (5/5).
Compound 11: orange solid, mp 162.4 °C, 1H NMR (200 MHz, CDCl3) d 4.43 (s,
2H); 7.52–7.69 (m, 8H); 7.72–7.77 (m, 2H); 7.92 (d, J = 8.5 Hz, 2H); 8.20 (s, 1H);
8.27 (d, J = 8.8 Hz, 2H). 13C NMR (50 MHz, CDCl3) d 54.7 (CH2); 124.1 (2xCH);
128.1 (2xCH); 128.7 (2xCH); 129.4 (4xCH); 130.0 (2xCH); 134.1 (CH); 134.4
(CH); 135.5 (C); 138.6 (C); 138.7 (C); 139.5 (C); 144.4 (CH); 148.6 (C). HRMS
Calcd for C21H17NO6S2 [M+NH4+]: 461.0836, Found: 461.0836. Compound 12:
yellow solid, mp 200.4 °C, 1H NMR (200 MHz, CDCl3) d 2.44 (s, 3H); 2.46 (s,
3H); 4,41 (s, 2H); 7,31–7.39 (m, 4H); 7.60–7.83 (m, 5H); 8.15 (s, 2H); 8.26 (d,
J = 8.8 Hz, 2H). 13C NMR (50 MHz, (CD3)2CO) d 20.7 (2xCH3); 53.7 (CH2); 123.6
(2xCH); 128.2 (2xCH); 128.8 (2xCH); 129.7 (2xCH); 129.8 (2xCH); 130.2
(2xCH); 136.5 (C); 136.8 (C); 137.0 (C); 139.6 (C); 143.4 (CH); 144.9 (C); 145.1
9. (a) Kornblum, N.; Pink, P.; Yorka, K. H. J. Am. Chem. Soc. 1961, 83, 2779–2780;
(b) Kornblum, N.; Pink, P. Tetrahedron 1963, 19(suppl. 1), 17–22.
10. Burt, B. L.; Freeman, D. J.; Gray, P. G.; Norris, R. K.; Randles, D. Tetrahedron Lett.
1977, 3063–3066.
11. Purified by silica gel chromatography with CH2Cl2/petroleum ether (5/5). New
products: Compound 2: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.75 (s, 6H);
3.10 (s, 2H); 7.53 (d, J = 8.9 Hz, 2H); 8.17 (d, J = 8.9 Hz, 2H). 13C NMR (50 MHz,
CDCl3) d 25.6 (2xCH3); 31.7 (CH2); 86.7 (C); 88.9 (C); 123.5 (2xCH); 129.5 (C);
132.5 (2xCH); 147.1 (C). Anal Calcd for C12H12N2O4: C, 58.06; H, 4.87; N, 11.29.
Found: C, 58.19; H, 5.01; N, 11. Compound 3: yellow oil, 1H NMR (200 MHz,
CDCl3) d 1,90 (s, 3H); 2,00 (s, 3H); 5.50 (s, 1H); 7.53 (d, J = 8.9 Hz, 2H); 8.17 (d,
J = 8.9 Hz, 2H). 13C NMR (50 MHz, CDCl3) d 21.4 (CH3); 25.1 (CH3); 89.9 (C);
93.5 (C); 104.7 (CH); 123.6 (2xCH); 131.1 (C); 131.8 (2xCH); 146.5 (C); 151.9
(C). Anal Calcd for C12H11NO2: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.57; H,
5.66; N, 6.86. Compound 4: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.71 (s, 6H);
3.76 (s, 2H); 6.76 (s, 1H); 7.32 (d, J = 8.5 Hz, 2H); 8.15 (d, J = 8.5 Hz, 2H). 13C
NMR (50 MHz, CDCl3) d 25.9 (2xCH3); 34.2 (CH2); 90.5 (C); 123.8 (2xCH); 128.6
(C); 148.2 (C). HRMS Calcd for
C
23H21NO6S2 [M+NH4+]: 489.1149, Found:
489.1144. Compound 13: yellow solid, mp 166.3 °C, 1H NMR (200 MHz, CDCl3)
d 4,43 (s, 2H); 7.47–7.57 (m, 4H); 7.68–7.74 (m, 4H); 7.86 (d, J = 8.6 Hz, 2H);
8.19 (s, 1H); 8.30 (d, J = 8.8 Hz, 2H). 13C NMR (50 MHz, CDCl3) d 54.7 (CH2);
124.2 (2xCH); 129.6 (2xCH); 129.7 (2xCH); 129.8 (2xCH); 130.0 (2xCH); 130.1
(2xCH); 135.1 (C); 137.1 (C); 137.6 (C); 138.4 (C); 141.1 (C); 141.5 (C); 145.1
(CH); 148.7 (C). HRMS Calcd for C21H15Cl2NO6S2 [M+NH4+]: 529.0056, Found:
529.0052.
14. (a) Chahrour, O.; Ashraf, A.; Lam, F.; Midgley, C.; Wang, S. Bioorg. Med. Chem.
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(2xCH); 138.4 (CH); 144.4 (C). HRMS Calcd for
302.0902, Found: 302.0906.
C
12H13ClN2O4 [M+NH4+]:
12. Purified by silica gel chromatography with CH2Cl2/petroleum ether (5/5).
Compound 5: yellow oil, 1H NMR (200 MHz, CDCl3) d 1.64 (m, 8H); 2.48 (m,