Thioimides: New reagents for effective synthesis of thiolesters from carboxylic acids

Article abstract of DOI:10.1021/jo801319x

(Chemical Equation Presented) Thioimides and carboxylic acids are used as the precursors for the convenient synthesis of thiolesters in the phosphine mediated process. Cyclic and acyclic thioimides show equal efficiency, furnishing the desired thiolesters in good to excellent yields. The general, highly efficient transformation tolerates various functional groups and the resulting thiolesters are obtained in high purity after a simple separation. The reaction scope has been demonstrated on the preparation of several highly functionalized target molecules.

Full text of DOI:10.1021/jo801319x

Thioimides: Reagents for Effective Synthesis of Thiolesters from
Carboxylic Acids.
Adam Henke and Jiri Srogl*
Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10, Prague
jsrogl@uochb.cas.cz
Supporting Information
Table of Contents
Page S2:
General Experimental
Page S23:
NMR Characterization of the Compounds
S1

General Experimental.
13
1H NMR and C NMR spectra were recorded at 400 MHz NMR spectrometer with solvent
1
13
1
13
residual peak (CDCl3: H = 7.24 ppm, C =77.23; (CD3)2CO: H = 2.05 ppm, C = 206,68
1
13
ppm; (CD3)2SO: H = 2.50 ppm, C = 39.51 ppm) as the internal reference unless otherwise
noted. Data are reported in the following order: chemical shifts are given
(δ ); multiplicities are indicated br (broadened), s (singlet), d (doublet), t (triplet), q (quartet),
m (multiplet), app (apparent); coupling constants, J, are reported in Hz. Peaks in IR are
reported in cm-1 with the following relative intensities: s (strong, 67-100%), m (medium, 40-
67%), w (weak, 10-40%). Melting points were determined on a Boetius block and are not
corrected. Column chromatography procedures were followed using 70-230 µm silica gel.
Visualization was effected with ultraviolet light.
Solvents such as DMF, DMA, THF, dioxane, dichlormethane for reaction media were dried
over 4 Ǻ molecular sieves and titrated for water level with a Karl Fischer Coulometer (water
content below 10 ppm) and purged with dry N2 or Ar before using.
S2

COOH
Cl
COCl
Cl
SOCl2
O2N
O2N
COCl
Cl
O2N
2-Chloro-5-nitrobenzoyl chloride (3). A mixture of 2-chloro-5-nitrobenzoic
acid (20.1 g; 100 mmol) and SOCl2 (36 ml; 500 mmol) was heated 8 h at 70 °C. SOCl2 was
evaporated and solid was dissolved in small amount of dichloromethane. Hexane was added
and the mixture was allowed to stand for 8 h at 0 °C. Product was filtered and washed with
small amount of cold hexane. After drying white crystalline produkt was obtained in 95%
1
yield (20.9 g). M.p.55-57 °C, (lit. 60 °C)1. H NMR (400 MHz, CDCl3): δ 8.90 (d, J = 2.6,
1H), 8.36 (dd, J = 2.6, 8.8, 1H), 7.71 (d, J = 8.8, 1H).
General Procedure for Preparing Compounds 4a – 4f
O
O2N
COCl
Cl
O2N
R
RNH2
N
H
method A or B
Cl
4
3
Method A: Amine (12 mmol) was dissolved in dry pyridine (10 ml) and cooled down to
0 °C. 2-Chloro-5-nitrobenzoyl chloride (9.23 mmol) was added at once to the reaction
mixture. The mixture was stirred with the temperature slowly rising to room temperature. The
stirring was continued for 6 hours under drying tube. After taht it was poured in ice and
resulting solid was filtred, washed first with water and than with 5% aquaeous hydrochloric
acid. The product was air dryed.
Method B: To a suspension of amine (30 mmol) and potassium carbonate (30 mmol) in
dried THF (25 ml) cooled down to 0 °C was dropwise added solution of 2-chloro-5-
1 Cohen, J. B.; Armes, H. P. J. Chem. Soc., Trans. 1906, 89, 458.
S3

nitrobenzoyl chloride (10 mmol) in dry THF (5 ml). The reaction mixture was stirred under
drying tube at 0 °C for 15 min followed by stirring at room temperature for 1 h. Solid was
separated and washed with small amount of THF. Hexane was added until the first
opalescence was apparent. Then was the mixture allowed to stay for 3 h at 0 °C. Product was
filtred and dried open to the air.
O
O2N
N
H
Cl
2-Chloro-N-(2,6-dimethylphenyl)-5-nitrobenzamide
(4a).
Method A. From 2,6-dimethylaniline (3.30 g; 27.30 mmol) white crystalline product was
obtained after recrystallization from ethanol in 90% yield (6.21 g). M.p.193-194.5 °C, (lit.
1
194-195 °C)2. H NMR (400 MHz, CDCl3): δ 8.59 (d, J = 2.7, 1H), 8.25 (dd, J = 2.7, 8.8,
1H), 7.66 (d, J = 8.8, 1H), 7.43 (br s, 1H), 7.20 – 7.09 (m, 3H), 2.34 (s, 6H).
O
O2N
OH
N
H
Cl
2-Chloro-N-(2-hydroxyethyl)-5-nitrobenzamide
(4b).
Method B. From 2-aminoethanol (4.1 ml ; 68.10 mmol) yellowish crystalline product was
1
obtained in 81% yield (4.52 g). M.p.155-157 °C. H NMR (400 MHz, DMSO): δ 8.69 (br t,
J = 5.1, 1H), 8.31-8.24 (m, 2H), 7.81 (d, J = 8.3, 1H), 4.80 (t, J = 5.6, 1H), 3.53 (app q,
13
J = 5.9, 2H), 3.32 (app q, J = 5.9, 2H). C NMR (101 MHz, DMSO): δ 164.4, 146.0, 137.9,
137.1, 131.2, 125.3, 123.8, 59.5, 42.1. IR (CHCl3): 3625 w (OH), 3437 w (NH), 1670 s
(CONH), 1528 s (CONH+NO2), 1350 s (NO2), 1068 w (OH) cm-1. Anal. calcd for
C9H9ClN2O4: C, 44.19; H, 3.71; N, 11.45. Found: C, 44.01; H, 3.71; N, 11.17.
O
O2N
N
H
Cl
N-Allyl-2-chloro-5-nitrobenzamide (4c). Method A. From
allylamine (4.0 ml ; 53.20 mmol) yellowish crystalline product was obtained in 92% yield
2 Yale, H.L. J. Heterocycl. Chem.1971, 8, 193.
S4

1
(9.02 g). M.p.141-142.5 °C. H NMR (400 MHz, CDCl3): δ 8.50 (d, J = 2.7, 1H), 8.20 (dd,
J = 2.7, 8.8, 1H), 7.59 (d, J = 8.8, 1H), 6.26 (br s, 1H), 5.93 (ddt, J = 5.7, 10.3, 17.0, 1H),
5.30 (app qd, J = 1.5, 17.2, 1H), 5.23 (app qd, J = 1.3, 10.3, 1H), 4.11 (app tt, J = 1.5, 5.8,
2H). 13C NMR (101 MHz, Acetone): δ 165.5, 148.0, 139.5, 138.9, 135.9, 132.7, 126.7, 125.3,
116.8, 43.1. IR (CHCl3): 3440 w (NH), 1672 s (CONH), 1647 m (C=C), 1528 s
(CONH+NO2), 1349 s (NO2) cm-1. Anal. calcd for C10H9ClN2O3: C, 49.91; H, 3.77; N, 11.64.
Found: C, 49.56; H, 3.67; N, 11.19.
O
O2N
N
H
Cl
2-Chloro-N-isopropyl-5-nitrobenzamide (4d). Method A. From
allylamine (4.0 ml ; 41.36 mmol) yellowish crystalline product was obtained in 96% yield
1
(7.41 g). M.p.186-186.5 °C. H NMR (400 MHz, CDCl3): δ 8.42 (d, J = 2.7, 1H), 8.16 (dd,
J = 2.7, 8.8, 1H), 7.55 (d, J = 8.8, 1H), 5.98 (br s, 1H), 4.35 – 4.22 (m, 1H), 1.27 (d, J = 6.6,
13
6H). C NMR (101 MHz, CDCl3): δ 163.6, 146.7, 137.7, 137.1, 131.5, 125.6, 125.2, 42.9,
22.8. IR (CHCl3): 3428 w (NH), 2978 w (CH3), 1668 s (CONH), 1528 s (CONH+NO2), 1350
s (NO2) cm-1. Anal. calcd for C10H11ClN2O3: C, 49.50; H, 4.57; N, 11.54. Found: C, 49.22; H,
4.47; N, 11.23.
O
O2N
N
H
OH
Cl
2-Chloro-N-(2-hydroxyphenyl)-5-nitrobenzamide
(4e).
2-Aminophenol (6.0 g; 54.54 mmol) was disolved in dry THF (40 ml) cooled down to 0 °C.
2-Chloro-5-nitrobenzoyl chloride (4.0 g; 18.18 mmol) was dropwise added to a solution of
amine. The reaction mixture was stirred under drying tube at 0 °C for 3 h and then it was
quenched with 5% aquaeous hydrochloric acid. Solid was filtered and two times washed with
5% aquaeous hydrochloric acid followed by water. After driyng yellow solid product was
1
obtained in 96% yield (5.1 g). M.p.187-191 °C, (lit. 189-192 °C)3. H NMR (400 MHz,
Acetone): δ 9.48 (br s, 1H), 8.96 (s, 1H), 8.59 (d, J = 2.7, 1H), 8.36 (dd, J = 2.8, 8.8, 1H),
3 Nagarajan, K. et al. Indian J. Chem. 1974,12, 227.
S5

8.01 (dd, J = 1.5, 8.0, 1H), 7.86 (d, J = 8.8, 1H), 7.11 – 7.04 (m, 1H), 6.98 (dd, J = 1.4, 8.1,
1H), 6.92 (app dt, J = 1.5, 8.4, 1H).
O
O2N
N
H
Cl
2-Chloro-5-nitro-N-phenylbenzamide (4f). Method A. From
aniline (3.30 g; 27.30 mmol) white crystalline product was obtained after recrystallization
1
from ethanol in 90% yield (6.21 g). M.p.158.5-159 °C, (lit. 158 °C)4. H NMR (400 MHz,
CDCl3): δ 8.58 (d, J = 2.7, 1H), 8.24 (dd, J = 2.7, 8.8, 1H), 7.83 (br s, 1H), 7.66-7.58 (m, 3H),
7.39 (app t, J = 7.9, 2H), 7.20 (t, J = 7.4, 1H).
General Procedure for Preparing Coumpounds 5a – 5f-1
O
S
O
R
O2N
R
O2N
N
N
H
t-BuSH
H
NaOH / DMF
Cl
5
4
O
S
O2N
N
H
2-(tert-Butylthio)-N-(2,6-dimethylphenyl)-5-nitrobenzamide (5a).
Amide (4a) (6.43 mmol; 1.96 g) was added to the solution of tert-butylthiol (7.72 mmol;
0.70 g; 0.5 ml) and sodium hydroxide (7,07 mmol; 0.28 g) in DMF (10 ml) at 0 °C. It was
stirred at 0 °C for 3 h. After that tert-butylthiol (20 mol%) was added and it was stirred for
another 0.5 h. The mixture was poured in to the ice cold 5% hydrochloric acid, the
precipitated solid was filtered and washed with water. After drying pure tert-butythiolether
was obtained as a yellowish crystalline solid in 96% yield (2.20 g). M.p.192-194 °C (ethanol).
1H NMR (400 MHz, CDCl3): δ 8.82 (d, J = 2.6, 1H), 8.54 (br s, 1H), 8.24 (dd, J = 2.6, 8.5,
13
1H), 7.82 (d, J = 8.5, 1H), 7.19 – 7.08 (m, 3H), 2.35 (s, 6H), 1.40 (s, 9H). C NMR (101
4 Meisenheimer, J; Zimmermann, P; v. Kummer, U. Justus Liebigs Ann. Chem. 1926, 446, 205.
S6

MHz, DMSO): δ 164.7, 146.3, 143.9 ,140.0, 136.6, 135.5, 134.4 , 127.8, 126.8, 123.5, 121.9.
IR (KBr): 3244 m (NH), 2967 w (CH3), 1651 s (CONH), 1531 s (CONH), 1510 s (NO2), 1396
w (CH3), 1346 s (NO2), 1317 m (CONH) cm-1. Anal. calcd for C19H22N2O3S: C, 63.66;
H, 6.19; N, 7.81. Found: C, 63.58; H, 5.96; N, 7.60.
O
O2N
OH
N
H
S
2-(tert-Butylthio)-N-(2-hydroxyethyl)-5-nitrobenzamide (5b).
The general procedure was used employing amide (4b) (3.2 g; 13.08 mmol) and the reaction
was complete after 3 h. The product was obtained as a yellowish solid in 79% yield (3.11 g).
1
M.p. 103.5-105 °C (toluene/hexane). H NMR (400 MHz, Acetone): δ 8.41 (d, J = 2.6, 1H),
8.25 (dd, J = 2.7, 8.5, 1H), 8.01 (br s, 1H), 7.91 (d, J = 8.5, 1H), 3.92 (t, J = 5.5, 1H), 3.78-
3.72 (m, 2H), 3.54 (q, J = 5.7, 2H), 1.36 (s, 9H). 13C NMR (101 MHz, Acetone): δ 167.6,
148.8, 145.3, 140.5, 140.0, 124.8, 124.6, 62.0, 49.9, 44.0, 32.0. IR (CHCl3): 3627 w (OH),
3437 w (NH), 3287 w (NH), 2966 w (CH3), 1658 s (CONH), 1526 s (NO2), 1472 w (CH3),
1367 m (CH3), 1350 s (NO2), 1067 w (OH) cm-1. Anal. calcd for C13H18N2O4S: C, 52.33; H,
6.08; N, 9.39. Found: C, 52.12; H, 6.07; N, 9.27.
O
O2N
N
H
S
N-Allyl-2-(tert-butylthio)-5-nitrobenzamide (5c). The general
procedure was used employing amide (4c) (8.80 g; 36.56 mmol) and the reaction was
complete after 4 h. The product was obtained as a yellowish solid in 84% yield (9.04 g). M.p.
1
99-102 °C (EtOAc/hexane). H NMR (400 MHz, Acetone): δ 8.32 (d, J = 2.5, 1H), 8.25 (dd,
J = 2.7, 8.5, 1H), 7.91 (d, J = 8.6, 1H), 7.91 (br s, 1H), 6.05 – 5.93 (m, 1H), 5.36 (app dq,
J = 1.7, 17.2, 1H), 5.14 (app dq, J = 1.5, 10.3, 1H), 4.05 (app tt, J = 1.6, 5.7, 2H), 1.36 (s,
9H). 13C NMR (101 MHz, Acetone): δ 167.3, 148.7, 145.6, 140.8, 139.6, 136.2, 124.7, 124.4,
116.8, 49.8, 43.4, 32.1. IR (CHCl3): 3436 w (NH), 3299 w (NH), 3089 w (=CH2) 2979 w
(CH3), 2967 w (CH3), 1661 s (CONH), 1527 s (NO2), 1472 w (CH3), 1367 m (CH3), 1349 s
(NO2) cm-1. Anal. calcd for C14H18N2O3S: C, 57.12; H, 6.16; N, 9.52. Found: C, 56.90; H,
6.08; N, 9.35.
S7

O
S
O2N
N
H
2-(tert-Butylthio)-N-i-propyl-5-nitrobenzamide (5d). The general
procedure was used employing amide (4d) (6.80 g; 36.56 mmol) and the reaction was
complete after 4 h. The product was obtained as a beige solid in 97% yield (8.06 g). M.p. 151-
1
151.5 °C (EtOAc/hexane). H NMR (400 MHz, CDCl3): δ 8.76 (d, J = 2.6, 1H), 8.16 (dd,
J = 2.7, 8.5, 1H), 7.72 (d, J = 8.5, 1H), 7.29 (br s, 1H), 4.21-4.34 (m, 1H), 1.32 (s, 9H), 1.28
13
(d, J = 6.6, 6H). C NMR (101 MHz, CDCl3): δ 164.5, 148.1, 142.4, 139.7, 137.7, 125.3,
123.8, 50.1, 42.6, 31.0, 22.6. IR (CHCl3): 3425 w (NH), 3288 w (NH), 2972 m (CH3), 1657 s
(CONH), 1527 s (NO2), 1467 m (CH3), 1367 m (CH3), 1350 s (NO2) cm-1. Anal. calcd for
C14H20N2O3S: C, 56.73; H, 6.80; N, 9.45; S, 10.82. Found: C, 56.61; H, 6.78; N, 9.33;
S,10.76.
O
O2N
N
H
OH
S
2-(tert-Butylthio)-N-(2-hydroxyphenyl)-5-nitrobenzamide (5e).
The general procedure was used employing amide (4e) (5.00 g; 36.56 mmol) and the reaction
was complete after 5 h. The product was obtained as a beige solid in 81% yield (4.84 g). M.p.
1
155-156 °C (ethanol/hexane). H NMR (400 MHz, Acetone): δ 10.09 (br s, 1H), 9.04 (s, 1H),
8.73-8-69 (m, 1H), 8.34 (dd, J = 2.7, 8.5, 1H), 8.03-7.96 (m, 2H), 7.11 – 7.03 (m, 1H), 6.99
13
(dd, J = 1.4, 8.1, 1H), 6.95 – 6.88 (m, 1H), 1.37 (s, 9H). C NMR (101 MHz, Acetone): δ
166.0, 149.3, 149.3, 144.1, 140.8, 140.1, 127.8, 127.0, 125.6, 125.5, 123.4, 121.3, 117.9, 50.6,
31.9. IR (CHCl3): 3596 w (OH), 3403 w (NH), 3217 w (NH), 2979 m (CH3), 2967 m (CH3),
1645 s (CONH), 1548 m (CONH), 1530 s (NO2), 1472 w (CH3), 1368 m (CH3), 1348 s (NO2)
cm-1. Anal. calcd for C17H18N2O4S: C, 58.94; H, 5.24; N, 8.09; S, 9.26. Found: C, 58.78; H,
5.14; N, 8.00; S, 9.19.
S8

O
S
O2N
N
H
2-(tert-Butylthio)-5-nitro-N-phenylbenzamide (5f-1). The
general procedure was used employing amide (4f) (12.00 g; 43.37 mmol) and the reaction was
complete after 6 h. The product was obtained as a yellow solid in 68% yield (9.01 g). M.p.
142-145 °C (EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ 9.90 (br s, 1H), 9.00 (d, J = 2.6,
1H), 8.23 (dd, J = 2.7, 8.4, 1H), 7.80 (d, J = 8.4, 1H), 7.67 (d, J = 7.9, 2H), 7.39 (t, J = 7.9,
13
2H), 7.17 (t, J = 7.4, 1H), 1.33 (s, 9H). C NMR (101 MHz, CDCl3): δ 163.1, 148.7, 141.7,
140.8, 137.7, 137.3, 129.5, 126.5, 125.2, 124.7, 120.4, 51.2, 31.1. IR (KBr): 3314 m (NH),
3240 m (NH), 2963 m (CH3), 1654 s (CONH), 1548 s (CONH), 1531 s (NO2), 1365 m (CH3),
1344 s (NO2), 1325 s (CONH) cm-1. Anal. calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48;
S, 9.70. Found: C, 61.66; H, 5.41; N, 8.18; S, 9.63.
O
S
O
S
O
S
H
O2N
H2N
Ph
N
PhCOCl, K2CO3
THF
N
H
Fe
AcOH
N
H
N
H
O
O
S
H
N
N
H
O
5-Benzamido-2-(tert-butylthio)-N-phenylbenzamide (5f-2).
Iron powder (0.20 g, 3.58 mmol) was added to a solution of amide (5f-1) in glacial acetic acid
(20 ml). Suspension was stirred at 40 °C under argon. During 15 min the suspension
transformed to a braun solution. After 1 h another portion of iron powder (0.20 g, 3.58 mmol)
was added. After 3 h pH was adjusted to 7-8 by adding a solution of potassium carbonate. The
aqueous layer was extracted with dichlormethane (3x20 ml). The combined organics were
dried with MgSO4, filtered and solvent was evaporated. Crude amine was disolved in dry
THF (10 ml) and potassium carbonate was added followed by the benzoyl chloride at 0 °C.
The reaction mixture was stirred 1 h under argon at 0 °C and then 1 h at the room
temperature. Solid was filtered and washed with THF. Half of solvent was evaporated and
hexan was added to first opalescence. The product was separated by filtration. After
S9

recrystallization the product was obtained as a white solid in 75% yield (0.54 g). M.p. 215-
217 °C (EtOAc/toluen). [complex 2:1 5f-2:EtOAc] 1H NMR (400 MHz, CDCl3): δ 10.56 (s,
1H), 8.39 (dd, J = 2.6, 8.4, 1H), 8.33 (s, 1H), 8.18 (d, J = 2.6, 1H), 7.88-7.83 (m, 2H), 7.70-
7.66 (m, 2H), 7.64 (d, J = 8.4, 1H), 7.52 (tt, J = 1.3, 7.5, 1H), 7.44 – 7.38 (m, 2H), 7.38 – 7.32
(m, 2H), 7.14 (tt, J = 1.1, 7.9, 1H), 4.10 (q, J = 7.1, 1H), 2.02 (s, 2H), 1.25 (s, 9H), 1.24 (t,
13
J = 7.1, 3H). C NMR (101 MHz, CDCl3) δ 166.2, 164.8, 142.0, 140.3, 140.2, 138.2, 134.6,
132.4, 129.4, 129.1, 127.4, 124.8, 123.5, 122.9, 122.3, 120.4, 60.6, 49.5, 30.8, 21.3, 14.4. IR
(KBr): 3319 m (NH), 3287 m (NH), 3249 m (NH), 3194 m (NH), 2973 m (CH3), 1740 s
(COOEt), 1673 s (CONH), 1651 s (CONH), 1549 s (CONH), 1471 m (CH3), 1321 s (CONH)
.
cm-1. Anal. calcd for 2xC17H18N2O3S C4H8O2: C, 69.62; H, 6.29; N, 6.24. Found: C, 69.52;
H, 6.36; N, 6.20.
General Procedure for Preparing Compounds 1a – 1h
O
O
N R
O2N
R
O2N
Me3SiCl / DMSO
CH2Cl2
N
H
S
S
5
1
O
O2N
N
S
2-(2,6-Dimethylphenyl)-5-nitrobenzo[d]isothiazol-3(2H)-one
(1a). TMSCl (3.2 ml, 25.03 mmol) was added to a solution of amide (5a) (6.90 g, 19.25
mmol) and DMSO (2 ml, 28.88 mmol) in dry dichlormethane (60 ml). The reaction mixture
was stirred at room temperature under drying tube. The reaction was complete after 6 h.
Hexane was added and the mixture was allowed to stand for 3 h. The produkt was separated
by filtration and washed with hexane. After recrystallization from ethanol the product was
obtained as a yellowish solid in 74% yield (4.28 g). M.p. 241-242 °C (ethanol). 1H NMR (400
MHz, DMSO): δ 8.61 (d, J = 1.8, 1H), 8.55 (dd, J = 2.1, 8.9, 1H), 8.37 (d, J = 8.9, 1H), 7.34
13
(t, J = 7.4, 1H), 7.25 (d, J = 7.4, 2H), 2.11 (s, 6H). C NMR (101 MHz, DMSO): δ 162.3,
148.1, 145.7, 137.4, 132.9, 129.8, 128.6, 126.4, 124.3, 124.1, 121.4, 17.4. IR (KBr): 2985 m
S10

(CH3), 1675 s (CON), 1659 s (CON), 1516 s (NO2), 1377 w (CH3), 1344 s (NO2) cm-1.
Anal. calcd for C15H12N2O3S: C, 59.99; H, 4.03; N, 9.33; S, 10.68. Found: C, 60.08; H, 4.05;
N, 9.28; S, 10.66.
O
O2N
OH
N
S
2-(2-Hydroxyethyl)-5-nitrobenzo[d]isothiazol-3(2H)-one (1b).
The general procedure was used employing amide (5b) (3.0 g; 10.05 mmol) and the reaction
was complete after 3.5 h. The product was obtained as a yellow solid in 97% yield (2.30 g).
M.p. 195-196 °C. 1H NMR (400 MHz, DMSO): δ 8.51 (d, J = 2.3, 1H), 8.46 (dd, J = 2.3, 8.9,
1H), 8.25 (d, J = 8.9, 1H), 5.13 (t, J = 5.4, 1H), 3.92 (t, J = 5.3, 2H), 3.68 (app q, J = 5.3, 2H).
13C NMR (101 MHz, DMSO): δ 163.4, 147.9, 145.3, 125.6, 124.5, 123.4, 120.7, 59.5, 46.3.
IR (KBr): 3486 s (OH), 1653 s (CON), 1518 s (NO2), 1336 s (NO2), 1072 m (C-OH) cm-1.
Anal. calcd for C9H8N2O4S: C, 45.00; H, 3.36; N, 11.66; S, 13.35. Found: C, 44.75; H, 3.31;
N, 11.37; S, 13.58.
O
O2N
N
S
2-Allyl-5-nitrobenzo[d]isothiazol-3(2H)-one (1c). The general
procedure was used employing amide (5c) (4.0 g; 13.59 mmol) and the reaction was complete
after 8 h. After recrystallization from ethanol the product was obtained as a yellow solid in
90% yield (2.90 g). M.p. 123-123.5 °C. 1H NMR (400 MHz, CDCl3): δ 8.82 (d, J = 2.1, 1H),
8.40 (dd, J = 2.1, 8.8, 1H), 7.70 (d, J = 8.8, 1H), 5.91 (ddt, J = 6.2, 10.1, 16.7, 1H), 5.40 –
13
5.27 (m, 2H), 4.49 (d, J = 6.2, 2H). C NMR (101 MHz, CDCl3): δ 163.8, 146.6, 146.2,
131.8, 126.3, 125.4, 122.7, 121.6, 120.5, 46.7. IR (KBr): 1653 s (CON), 1641 s (C=C), 1511 s
(NO2), 1411 m (=CH2), 1340 s (NO2), 1295 s (=CH-), 915 s (=CH2) cm-1. Anal. calcd for
C10H8N2O3S: C, 50.84; H, 3.41; N, 11.86; S, 13.57. Found: C, 50.54; H, 3.33; N, 11.59; S,
13.31.
S11

O
O2N
N
S
2-Isopropyl-5-nitrobenzo[d]isothiazol-3(2H)-one
(1d).
The
general procedure was used employing amide (5d) (4.0 g; 13.50 mmol) and the reaction was
complete after 8 h. After recrystallization from ethanol the product was obtained as a yellow
solid in 92% yield (2.85 g). M.p. 164-165 °C. 1H NMR (400 MHz, DMSO): δ 8.03 (d, J = 2.2,
1H), 8.00 (dd, J = 2.3, 8.9, 1H), 7.82 (d, J = 8.8, 1H), 4.38 – 4.25 (m, 1H), 0.93 (d, J = 6.7,
13
6H). C NMR (101 MHz, DMSO): δ 162.6, 146.8, 145.5, 125.6, 125.4, 123.7, 120.6, 46.1,
21.8. IR (KBr): 2982 m (CH3), 1656 s (CON), 1517 s (NO2), 1339 s (NO2), 1330 s (CH), 843
s (NO2) cm-1. Anal. calcd for C10H10N2O3S: C, 50.41; H, 4.23; N, 11.76; S, 13.46. Found: C,
50.24; H, 4.04; N, 11.45; S, 13.43.
O
O2N
N
S
HO
2-(2-Hydroxyphenyl)-5-nitrobenzo[d]isothiazol-3(2H)-one (1e).
The general procedure was used employing amide (5e) (4.5 g; 13.00 mmol) and the reaction
was complete after 5 h. The product was obtained as a yellow solid in 94% yield (3.51g). M.p.
1
170-172 °C. H NMR (400 MHz, DMSO): δ 10.13 (s, 1H), 8.57 (d, J = 2.3, 1H), 8.54 (dd,
J = 2.4, 8.9, 1H), 8.30 (d, J = 8.9, 1H), 7.38 (dd, J = 1.6, 7.8, 1H), 7.33 (td, J = 1.7, 7.8, 1H),
7.03 (dd, J = 1.2, 8.2, 1H), 6.93 (td, J = 1.3, 7.6, 1H). 13C NMR (101 MHz, DMSO): δ 162.9,
154.1, 148.3, 145.5, 130.7, 130.1, 126.1, 124.4, 123.6, 122.3, 121.2, 119.4, 117.0. IR (KBr):
3100 m (OH), 1641 s (CON), 1523 s (NO2), 1515 s (NO2), 1351 s (NO2), 1335 s (NO2) cm-1.
Anal. calcd for C13H8N2O4S: C, 54.16; H, 2.80; N, 9.72. Found: C, 53.83; H, 2.73; N, 9.44.
O
N
H
N
O
S
N-(3-Oxo-2-phenyl-2,3-dihydrobenzo[d]isothiazol-5-
yl)benzamide (1f). The general procedure was used employing amide (5f-2) (1.37 g; 3.39
mmol) and the reaction was complete after 5 h. After washing by ethanol the product was
1
obtained as a white solid in 81% yield (0.95 g). M.p. 224-225 °C (aceton). H NMR (400
MHz, DMSO): δ 10.57 (s, 1H), 8.54 (d, J = 2.0, 1H), 8.13 (dd, J = 2.1, 8.8, 1H),
S12

13
8.05 – 7.98 (m, 3H), 7.75 – 7.70 (m, 2H), 7.65 – 7.50 (m, 5H), 7.41 – 7.34 (m, 1H). C NMR
(101 MHz, DMSO): δ 165.7, 163.2, 137.6, 137.3, 134.6, 134.5, 131.8, 129.4, 128.4, 127.7,
126.9, 125.4, 124.7, 124.3, 122.1, 116.6. IR (KBr): 3288 m (NH), 1653 s (CONH), 1531 s
(CONH), 1515 s (NO2), 1345 m (CONH) cm-1. Anal. calcd for C20H14N2O2S: C, 69.35; H,
4.07; N, 8.09. Found: C, 69.17; H, 3.92; N, 7.80.
General Procedure for Preparing N-(arylthio)succinimides 1g-1h5
O
O
benzene
2. Et3N
+
R-SH
N Cl
N S
R
O
O
A solution of thiole (20 mmol) in benzene (20 ml) at room temperature was added, all at once,
to a suspension of N-chlorosuccinimide (20 mmol) in benzene (110 ml). After being stirred
for 5 min, the mixture turned red or orange and the temperature rose to 30-35 °C. After the
temperature had been depressed to 25 °C, a solution of triethylamine (21 mmol) in benzene
(20 ml) was added, drop by drop, over a period of 5 min at 20-30 °C with cooling. The
reaction mixture faded. It was then allowed to stand for 30 min, washed thoroughly with
water, and the extract was then dried over anhydrous magnesium sulfate. After the romoval
three third of solvent, hexane was added and it was allowed to stand for 3 h. Produkt was
filtered and washed with hexane.
O
N S
1-(p-Tolylthio)pyrrolidine-2,5-dione (1g).5 The general procedure was used
O
employing 4-methylbenzenthiol (5.70 g; 45.89 mmol). The product was obtained as a white
1
solid in 62% yield ( 6.18 g). M.p. 113-113.5 °C (toluene/hexane), (lit. 114.5-115 °C)5. H
5 Abe, Y.; Nakabayashi, T.; Tsurugi, J. Bull. Chem. Soc. Jpn. 1973, 46, 1898.
S13

NMR (400 MHz, CDCl3): δ 7.58 (d, J = 8.1, 2H), 7.13 (d, J = 8.0, 2H), 2.76 (s, 4H), 2.32 (s,
3H).
O
N
N
N S
O
1-(p-Tolylthio)pyrrolidine-2,5-dione (1h). The general procedure was
used employing 4,6-dimethylpyrimidine-2-thiol (2.67 g; 19.04 mmol). The product was
1
obtained as a white solid in 40% yield (1.87 g). M.p. 165-166 °C (toluene/hexane). H NMR
13
(400 MHz, CDCl3): δ 6.71 (s, 1H), 2.94 (s, 4H), 2.33 (s, 6H). C NMR (101 MHz, CDCl3): δ
176.4, 168.1, 166.8, 117.6, 29.1, 24.0. IR (CHCl3): 3026 m (=C-H), 1802 m (CONCO), 1740
s (CONCO), 1588 s, 1533 s, 1431 s (CH2) cm-1. Anal. calcd for C10H11N3O2S: C, 50.62; H,
4.67; N, 17.71; S, 13.51. Found: C, 50.54; H, 4.62; N, 17.48; S, 13.32.
Bu3PH BF4
Tributylphosphonium tetraflouroborate (6).6 HBF4 (48 wt% aqueous solution;
4.0 ml, 31 mmol) was added to a solution of tributyphosphine (5.0 mL, 20 mmol) in
dichloromethane (50 ml), and the resulting mixture was stirred vigorously for 10 min. The
organic layer was then separated from the aqueous layer, dried over magnesium sulfate, and
filtered. Removal of the solvent provided the title compound in 96% yield (5.71 g) as an
1
colorless solid. M.p. 51-52 °C, (lit. 51-52 °C)6. H NMR (400 MHz, CDCl3): δ 6.74 – 5.42
(dm, JPH = 485.2, 1H), 2.31-2.18 (m, 6H), 1.72 – 1.39 (m, 12H), 1.03 – 0.84 (m, 9H).
Bu3PH PF6
Tributylphosphonium hexaflourophosphate (7). Tributylphosphonium
tetraflouroborate (6) (1.00 g; 3.44 mmol) was dissolved in methanol (5 ml) and water (3 ml)
was added. A solution was vigorously stirred a then was added a solution of ammonium
hexafluorophosphate (0.73 g; 4.48 mmol) in water (50 ml). The reaction was stirred
overnight, the resulting solid was separated by filtration, and washed two times with water.
After drying under vacuum was obtained white crystalline product in 83% yield (1,01 g). M.p.
6 Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295
S14

1
84-86 °C. H NMR (400 MHz, CDCl3): δ 5.91 (dm, JPH = 476.3, 1H), 2.27 – 2.16 (m, 6H),
31
1.65 – 1.43 (m, 12H), 0.94 (t, J = 7.2, 9H). P NMR (162 MHz, CDCl3, H3PO4 31P = 0): δ
14.1 (dm, JPH = 477.9), -143.7 (septet, JPF = 713.14).13C NMR (101 MHz, CDCl3): δ
24.8 (d, JCP= 4.9), 23.8 (d, JCP = 15.4), 16.4 (d, JCP = 46.7), 13.4 (s). IR (CHCl3): 2966 m
(CH3), 2936 m (CH2), 2877 m (CH3), 2418 w (P-H+), 848 s (P-F), 559 s (P-F) cm-1. Anal.
calcd for C12H28F6P2: C, 41.38; H, 8.10; P, 17.79. Found: C, 41.84; H, 8.33; P, 17.21.
General Procedure for Preparing Thiolesters 2a-2h
O
O
N R'
X
R'
X
R"COOH, Bu3P
THF
N
H
S
S
2a-h
1a-f
O
R"
Thioimide (1) (2.00 mmol) and corresponding carboxylic acid (1.20 mmol) were dissolved in
dry THF (10 ml) under argon. Bu3P (1.1 mmol) was added drop by drop to the reaction
mixture. After addition of the phosphine, the reaction mixture was stirred for another 10 min.
The mixture was then quenched with ice cold 5% hydrochloric acid (cca 50 ml) followed by
stirring for additional 2-3 h and then filtered.
O
O2N
N
H
S
S
O
S-2-(2,6-Dimethylphenylcarbamoyl)-4-nitrophenyl thiophene-2-
carbothioate (2a). The general procedure was used employing thioimide (1a) (400 mg; 1.57
mmol). After crystallization (benzen/aceton) the product was obtained as a yellowish
1
crystalline in 76% yield (490 mg). M.p. 211-214 °C. H NMR (400 MHz, Acetone): δ 9.31
(br s, 1H), 8.58 (d, J = 2.5, 1H), 8.45 (dd, J = 2.5, 8.6, 1H), 8.09-8.03 (m, 3H), 7.33 (t, J = 4.5,
13
1H), 7.13-7.09 (m, 3H), 2.33 (s, 6H). C NMR (101 MHz, Acetone): δ 180.7, 165.4, 149.6,
144.4, 141.8, 139.7, 137.2, 136.5, 135.7, 134.9, 134.3, 130.2, 129.4, 128.6, 125.7, 124.0, 19.3.
S15

IR (KBr): 3213 m (NH), 1676 s (COS), 1661 s (COS), 1646 s (CONH), 1539 s (CONH),
1518 s (NO2), 1348 s (NO2) cm-1. Anal. calcd for C20H16N2O4S2: C, 58.24; H, 3.91; N, 6.79;
S, 15.55. Found: C, 57.97; H, 3.81; N, 6.63; S, 15.36.
O
O2N
OH
N
H
S
O
S-2-(2-Hydroxyethylcarbamoyl)-4-nitrophenyl 3,7-dimethyl-
oct-6-enethioate (2b). Thioimide (1b) (400 mg; 1.65 mmol) and citronellic acid (340 mg;
2.00 mmol) were dissolved in dry THF (8 ml) under argon. Bu3P (0.45 ml; 1.83 mmol) was
added drop by drop to a reaction mixture. After the addition of phosphine was completed, the
reaction mixture was stirred for another 10 min. The mixture was then quenched with ice cold
5% hydrochloric acid (cca 50 ml) followed by stirring for additional 2h and then filtered. The
filtrate was extracted with dichloromethane (4x15 ml). The combined organics were dried
with MgSO4, filtered and solvent was evaporated. Crude product was purificated by column
chromatography (1:1 EtOAc:toluen + 3% MeOH). It was obtained yellowish solid product in
1
85% yield (560 mg). M.p. 83.5-85 °C (EtOH/hexane). H NMR (400 MHz, CDCl3): δ 8.38 (d,
J = 2.5, 1H), 8.24 (dd, J = 2.5, 8.5, 1H), 7.67 (d, J = 8.5, 1H), 6.49 (br s, 1H), 5.06 (t, J = 7.0,
1H), 3.77 (s, 2H), 3.55 (app dd, J = 5.5, 10.3, 2H), 2.70 (dd, J = 5.8, 14.9, 1H), 2.50 (dd,
J = 8.2, 14.9, 1H), 2.23 (br s, 1H), 2.10-1.90 (m, 3H), 1.67 (s, 3H), 1.59 (s, 3H), 1.44-1.31 (m,
13
1H), 1.31-1.19 (m, 1H), 0.98 (d, J = 6.7, 3H). C NMR (101 MHz, CDCl3): δ 196.2, 167.1,
148.2, 142.0, 137.5, 134.0, 132.2, 124.8, 124.0, 123.2, 61.8, 51.5, 43.0, 36.8, 31.1, 25.9, 25.5,
19.6, 17.9. IR (KBr): 3565 m (HO), 3291 s (NH), 1701 s (COS), 1647 s (CONH), 1541 s
(CONH), 1523 s (NO2), 1351 s (NO2) cm-1. Anal. calcd for C19H26N2O5S: C, 57.85; H, 6.64;
N, 7.10; S, 8.13. Found: C, 57.41; H, 6.49; N, 6.86; S, 8.25.
S16

O
S
O2N
N
H
Cl
O
NO2
S-2-(Allylcarbamoyl)-4-nitrophenyl 2-chloro-5-nitrobenzo-
thioate (2c). The general procedure was used employing thioimide (1c) (300 mg; 1.27 mmol).
After a crystallization (EtOAc/hexane) the product was obtained as a yellowish crystalline
1
solid in 92% yield (490 mg). M.p. 168-170 °C. H NMR (400 MHz, CDCl3): δ 8.60 (d,
J = 2.6, 1H), 8.45 (d, J = 2.4, 1H), 8.36 (dd, J = 2.5, 8.5, 1H), 8.33 (dd, J = 2.7, 8.8, 1H), 7.88
(d, J = 8.5, 1H), 7.69 (d, J = 8.8, 1H), 6.12 (br s, 1H), 5.90 (ddt, J = 5.9, 10.2, 16.1, 1H), 5.28
13
(dd, J = 1.2, 17.1, 1H), 5.20 (dd, J = 1.2, 10.2, 1H), 4.06 (app tt, J = 1.4, 5.9, 2H). C NMR
(101 MHz, CDCl3): δ 187.4, 165.7, 148.8, 146.4, 142.4, 138.3, 137.8, 137.3, 133.2, 132.6,
127.6, 125.2, 124.7, 123.2, 118.0, 43.0. IR (KBr): 3225 s (NH), 1708 s (COS), 1693 s (COS),
1639 s (CONH), 1560 s (CONH), 1529 s (NO2), 1350 s (NO2), 904 s (=CH2) cm-1. Anal.
calcd for C17H12ClN3O6S: C, 48.41; H, 2.87; N, 9.96; S, 7.60. Found: C, 47.88; H, 2.78; N,
9.61; S, 7.44.
O
O2N
N
H
S
O
HO
S-2-(Allylcarbamoyl)-4-nitrophenyl 2-hydroxy-3-methylbenzo-
thioate (2d). The general procedure was used employing thioimide (1c) (300 mg; 1.27
mmol). The crude product was purified by column chromatography (2:3 EtOAc:hexane). The
product was obtained as a white crystalline in 63% yield (300 mg). M.p. 142.5-145 °C.
1H NMR (400 MHz, Acetone): δ 10.71 (s, 1H), 8.45 (d, J = 2.5, 1H), 8.41 (dd, J = 2.6, 8.5,
1H), 8.01 (d, J = 8.5, 1H), 7.99 (br s, 1 H), 7.89 (d, J = 8.1, 1H), 7.52 (d, J = 7.4, 1H), 6.99 (t,
J = 7.7, 1H), 5.90 (ddt, J = 5.9, 10.2, 16.1, 1H), 5.24 (app qd, J = 1.7, 17.2, 1H), 5.04 (app qd,
J = 1.5, 10.3, 1H), 3.99 (app tt, J = 1.6, 5.7, 2H), 2.23 (s, 3H). 13C NMR (101 MHz, Acetone):
δ 195.1, 166.7, 159.4, 149.8, 144.6, 139.9, 139.1, 135.9, 134.1, 128.8, 128.0, 125.6, 124.2,
120.9, 120.0, 116.8, 43.4, 16.2. IR (KBr): 3405 w (OH), 3289 s (NH), 1649 s (COS+CONH),
S17

1641 s (COS+CONH), 1550 s (CONH), 1519 s (NO2), 1356 s (NO2), 910 m (=CH2) cm-1.
Anal. calcd for C18H16N2O5S: C, 58.05; H, 4.33; N, 7.52; S, 8.61. Found: C, 57.77; H, 4.24;
N, 7.31; S, 8.89.
O
O2N
N
H
S
O
(E)-S-2-(Isopropylcarbamoyl)-4-nitrophenyl 3-phenylprop-2-
enethioate (2e). The general procedure was used employing thioimide (1d) (400 mg; 1.68
mmol). After a crystallization (benzen/aceton) the product was obtained as a white
1
crystallinesolid in 84% yield (520 mg). M.p. 165-166.5 °C. H NMR (400 MHz, Acetone): δ
8.36 – 8.31 (m, 2H), 7.96-7.90 (m, 1H), 7.84-7.78 (m, 7.3, 2H), 7.75 (d, J = 15.8, 1H), 7.60
(br s, 1H), 7.53 – 7.44 (m, 3H), 7.07 (d, J = 15.8, 1H), 4.18 (m, 1H), 1.24 (d, J = 6.6, 6H).
13C NMR (101 MHz, Acetone): δ 186.6, 166.0, 149.2, 144.1, 144.0, 138.7, 135.8, 135.4,
132.6, 130.5, 130.3, 125.3, 125.1, 123.9, 43.2, 23.2. IR (KBr): 3280 s (NH), 1683 s (COS),
1667 s (COS), 1631 s (CONH), 1615 s (C=C), 1545 s (CONH), 1516 s (NO2), 1348 s (NO2),
1328 s (C-H), 963 s (=CH2) cm-1. Anal. calcd for C19H18N2O4S: C, 61.61; H, 4.90; N, 7.56; S,
8.66. Found: C, 61.21; H, 4.78; N, 7.33; S, 8.39.
O
O2N
N
H
S
O
S-2-(Isopropylcarbamoyl)-4-nitrophenyl benzothioate (2f). The
general procedure was used employing thioimide (1d) (400 mg; 1.68 mmol). After washing
by a small amount of cold ethanol the product was obtained as a yellowish crystalline solid in
1
95% yield (550 mg). M.p. 146-148 °C (EtOAc/hexane). H NMR (400 MHz, CDCl3): δ 8.40
(d, J = 2.5, 1H), 8.27 (dd, J = 2.5, 8.5, 1H), 7.99 (d, J = 7.8, 2H), 7.75 (d, J = 8.5, 1H), 7.65 (t,
J = 7.4, 1H), 7.51 (t, J = 7.8, 2H), 5.93 (br d, J = 7.5, 1H), 4.24-4.10 (m, 1H),
S18

13
1.10 (d, J = 6.6, 6H). C NMR (101 MHz, CDCl3): δ 190.0, 165.5, 148.8, 144.3, 138.2,
135.8, 134.9, 132.7, 129.3, 128.0, 124.6, 123.4, 42.4, 22.7. IR (CHCl3): 3420 w (NH), 2978 m
(CH3), 2875 w (CH3), 1677 s (COS), 1658 s (CONH), 1529 s (CONH+NO2), 1351 s (NO2)
cm-1. Anal. calcd for C17H16N2O4S: C, 59.29; H, 4.68; N, 8.13; S, 9.31. Found: C, 58.82; H,
4.57; N, 8.04; S, 9.36.
O
O2N
N
H
OH
S
O
S-2-(2-Hydroxyphenylcarbamoyl)-4-nitrophenyl benzothioate
(2g). The general procedure was used employing thioimide (1e) (220 mg; 0.76 mmol). After a
crystallization (EtOH/hexan) the product was obtained as a yellow crystalline solid in 70%
1
yield (210 mg). M.p. 176-178 °C. H NMR (400 MHz, CDCl3): δ 8.63 (d, J = 2.4, 1H), 8.38
(dd, J = 2.5, 8.5, 1H), 8.24 (br s, 1H), 8.02-7.97 (m, 2H), 7.85 (d, J = 8.5, 1H), 7.81 (s, 1H),
7.65 (app tt, J = 1.3, 7.5, 1H), 7.50 (t, J = 7.8, 2H), 7.14-7.05 (m, 2H), 6.98 (dd, J = 1.4, 8.1,
13
1H), 6.84 – 6.79 (m, 1H). C NMR (125.7 MHz, CDCl3): δ 189.6, 165.3, 148.7, 148.4,
142.3,138.4, 135.3,135.0,132.8, 129.2,128.0,125.3, 124.9,123.9, 122.3, 120.8, 119.5. IR
(KBr): 3365 m (NH), 3100 m (OH), 1687 s (COS), 1647 s (CONH), 1533 s (NO2), 1522 s
(CONH), 1341 s (NO2), 895 s (OC-S) cm-1. Anal. calcd for C20H14N2O5S: C, 60.91; H, 3.58;
N, 7.10. Found: C, 60.42; H, 3.53; N, 6.80.
O
H
N
N
H
O
S
O
S-4-Benzamido-2-(phenylcarbamoyl)phenyl benzothioate
(2h). The general procedure was used employing thioimide (1f) (500 mg; 1.44 mmol). After
washing small amount of cooled ethanol the product was obtained as a with crystalline solid
1
in 78% yield (510 mg). M.p. 231-233 °C (aceton). H NMR (400 MHz, DMSO): δ 10.64 (s,
1H), 10.49 (s, 1H), 8.15 (d, J = 2.3, 1H), 8.09 (dd, J = 2.3, 8.6, 1H), 8.04 – 7.99 (m, 2H),
S19

7.96 – 7.91 (m, 2H), 7.74 – 7.53 (m, 9H), 7.31 (t, J = 7.9, 2H), 7.07 (t, J = 7.4, 1H). 13C NMR
(101 MHz, DMSO): δ 189.0, 166.0, 165.7, 142.5, 140.7, 138.9, 137.6, 135.8, 134.4, 134.2,
132.0, 129.2, 128.7, 128.5, 127.8, 127.0, 123.7, 121.3, 119.6, 119.4, 118.1. IR (KBr): 3304 s
(NH), 3282 s (NH), 3253 s (NH), 1684 s (COS), 1651 s (CONH), 1549 s (CONH), 1532 s
(CONH) cm-1. Anal. calcd for C27H20N2O3S: C, 71.66; H, 4.45; N, 6.19; S, 7.09. Found: C,
71.31; H, 4.42; N, 5.95; S, 6.75.
O
R'
S
S
R'COOH, Bu3P
THF
R
N
R
O
O
1g-h
2i-l
S
O
S-p-Tolyl benzothioate (2i). The general procedure was used employing
thioimide (1g) (200 mg; 0.90 mmol). After drying the product was obtained as a white
crystalline solid in 89% yield (180 mg). M.p. 73-73.5 °C (lit. 75-76).7 1H NMR (400 MHz,
CDCl3): δ 8.02 – 7.96 (m, 2H), 7.55 (app tt, J = 1.3, 7.4, 1H), 7.44 (t, J = 7.7, 2H), 7.36 (d,
J = 8.1, 2H), 7.23 (d, J = 3.2, 2H), 2.37 (s, 3H).
S
O
N
S-p-Tolyl pyridine-3-carbothioate (2j). Thioimide (1g) (400 mg; 1.81
mmol) and nicotinic acid (270 mg; 2.17 mmol) were dissolved under argon in dry THF
(7 ml). Bu3P (0.49 ml; 2.00 mmol) was added drop by drop to the reaction mixture. After
addition of whole amount phosphine the mixture was stirred for additional 10 min. The
mixture was then quenched with ice cold 5% hydrochloric acid (cca 50 ml) followed by
stirring for additional 3 h and then extracted with EtOAc (3x30 ml). The combined organics
were dried with MgSO4, filtered and solvent was evaporated. Crude product was purified by
7
Wawzonek, S.; Kellen, J. N. J. Org. Chem. 1973, 38, 3627.
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column chromatography (3:2 EtOAc:hexan). It was obtained white solid in 79% yield
(325 mg). M.p. 47-48.5 °C (lit. 48-51 °C).8 1H NMR (400 MHz, CDCl3): δ 9.22 (d, J = 1.6,
1H), 8.80 (dd, J = 1.7, 4.8, 1H), 8.24 (ddd, J = 1.8, 2.2, 8.0, 1H), 7.42 (ddd, J = 0.8, 4.9, 8.0,
1H), 7.40 – 7.35 (m, 2H), 7.30-7.25 (m, 2H), 2.40 (s, 3H).
S
O
H
S-p-Tolyl methanethioate (2k). Thioimide (1g) (800 mg; 3.62 mmol) and
formic acid (0.17 ml; 4.34 mmol) were dissolved under argon in dry THF (5 ml). Bu3P (0.98
ml; 3.90 mmol) was added to the reaction mixture dropwise. After addition of whole amount
phosphine it was 10 min stirred. The mixture was quenched with ice cold 5% hydrochloric
acid (cca 50 ml) and extracted with EtOAc (4x20 ml). The combined organics were dried with
MgSO4, filtered and solvent was evaporated. Crude product was purified by column
chromatography (4:5 EtOAc:hexan). White oil was obtained in 58% yield (320 mg). 1H NMR
(400 MHz, CDCl3): δ 10.20 (s, 1H), 7.38 – 7.33 (m, 2H), 7.26-7.22 (m, 2H), 2.40 (s, 3H). (lit.
1H NMR (200 MHz, CDC13): 10.21 (s, 1 H), 7.23-7.40 (m, 4 H), 2.40 (s, 3 H).).9
N
N
S
I
O
S-4,6-dimethylpyrimidin-2-yl 2-iodobenzothioate (2l). The general
procedure was used employing thioimide (1h) (400 mg; 1.69 mmol). After crystallization
(EtOH/hexan) the product was obtained as a white crystalline in 91 % yield (570 mg). M.p.
143-146 °C. 1H NMR (400 MHz, CDCl3): δ 7.96 (dd, J = 0.6, 7.3, 1H), 7.81 (dd, J = 1.5, 7.8,
1H), 7.42 (dt, J = 0.8, 7.2, 1H), 7.16 (dt, J = 1.5, 6.9, 1H), 7.00 (s, 1H), 2.52 (s, 6H).
8 Miyaki, K.; Yamagishi, S. Chem.Abstr. 1957, 76, 3490.
9
Sprecher, M.; Nov, E. Synth. Commun. 1992, 22, 2949.
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13C NMR (101 MHz, CDCl3): δ 190.5, 168.9, 163.3, 141.5, 141.4, 133.1, 129.8, 128.2, 119.9,
92.1, 24.2. IR (KBr): 1698 s (COS), 1590 s, 1519 s, 1434 s, 1248 s, 1200 s, 893 s, 864 s, 762 s
cm-1. Anal. calcd for C13H11IN2OS: C, 42.18; H, 2.99; N, 7.57; S, 8.66. Found: C, 42.01; H,
2.98; N, 7.41; S, 8.82.
Selectivity of acylation
O
O
O2N
O2N
N
H
N
S
S
S
[Bu3PH] PF6
1d
S
2f
2i
PhCOOH
O
Ph
O
DMA
Ph
S
Thioimide (1d) (97 mg; 0.406 mmol), disulfide (100 mg; 0.406 mmol), benzoic acid (60 mg;
0.487 mmol) and naphtalene (internal standard, 74.5 mg; 0.581 mmol) were dissolved under
argon in dry DMA (2 ml). Solution of tributylphosphonium hexafluorophosphate (7) (150 mg;
0.426 mmol) in dry DMA (2 ml) was added dropwise to the reaction mixture. The mixture
was stirred for 3 days at room temperature. HPLC yield of product 2f was 61% and HPLC
yield of product 2i was 0%.
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NMR Characterization of Compounds
Page
entry
1H NMR 13C NMR
1a
1b
1c
1d
1e
1f
1h
2a
2b
2c
2d
2e
2f
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2g
2h
2l
4b
4c
4d
5a
5b
5c
5d
5e
5f-1
5f-2
7
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