Silica-gel-catalyzed conversion of stabilized phosphorus ylides to benzo[e][1,3]thiazocin derivatives

Article abstract of DOI:10.1080/10426500903376147

The reaction between triphenylphosphine, dialkylacetylenedicarboxylates, and N-benzoyl thiourea derivatives leads to intermediates such as vinyltriphenylphosphonium salts, which undergo Michael addition to produce the highly functionalized phosphorus ylid

Full text of DOI:10.1080/10426500903376147

Phosphorus, Sulfur, and Silicon, 185:1921–1925, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903376147
SILICA-GEL–CATALYZED CONVERSION OF STABILIZED
PHOSPHORUS YLIDES TO BENZO[e][1,3]THIAZOCIN
DERIVATIVES
Ali Souldozi1 and Ali Reza Dadrass2
1Department of Chemistry, Islamic Azad University–Urmia Branch, Urmia, Iran
2Chemistry Department, Faculty of Science, Urmia University, Urmia, Iran
The reaction between triphenylphosphine, dialkylacetylenedicarboxylates, and N-benzoyl
thiourea derivatives leads to intermediates such as vinyltriphenylphosphonium salts, which
undergo Michael addition to produce the highly functionalized phosphorus ylides containing
alkyl groups in excellent yields. Using silica gel as a catalyst, the conversion of the stabilized
phosphorus ylides to benzo[e][1,3]thiazocin derivatives in solvent free conditions at 90◦C in
fairly high yields is achieved.
Keywords Benzo[e][1,3]thiazocin derivatives; benzoyl isothiocyanate; N-benzoyl thiourea
derivatives; dialkylacetylenedicarboxylates; silica gel
INTRODUCTION
Phosphorus ylides are reactive compounds that participate in many reactions of value
in the synthesis of organic products.1–10 The development of the modern chemistry of
natural and physiologically active compounds would have been impossible without the
phosphorus ylides.11–16 These compounds have attained great significance as widely used
reagents for molecular building blocks by the formation of carbon–carbon double bonds.17
There are many studies on the reaction between trivalent phosphorus nucleophiles
and α,β-unsaturated carbonyl compounds using phenols, imides, amides, enols, oximes,
and alcohols as reaction adjuncts. Unsaturated esters such as dialkyl acetylenedicaboxylates
have been employed as Michael substrates in the presence of protic reagents.18–30 In this
article, we report the catalytic role of silica gel powder in the conversion of stabilized
phosphorus ylides to benzo[e][1,3]thiazocin derivatives in solvent-free thermal conditions
in fairly high yields.
RESULTS AND DISCUSSION
Our new synthetic method that leads to the title compounds is given in Scheme 1. The
reactions of N-benzoyl thiourea derivatives (3), which were derived from the addition of
Received 24 May 2009; accepted 25 September 2009.
This work was supported by the Urmia Islamic Azad University Research Council.
Address correspondence to Ali Souldozi, Department of Chemistry, Islamic Azad University–Urmia Branch,
PO Box 969, Urmia, Iran. E-mail: alisouldozi@yahoo.com
1921

1922
A. SOULDOZI AND A. R. DADRASS
O
S
O
S
R
C
N
H
N
R
N
+
R2NH
(2)
(1)
(3)
R'OOC
COOR'
Ph3P
(4)
R'OOC
C
C
COOR'
+
Ph3P
R
(5)
(6)
O
S
R'OOC
Ph3P
COOR'
N
H
N
R
+
(6)
(3)
O
S
O
S
R'OOC
Ph3P
COOR'
H
R
R
N
N
R
+
N
N
R
(7)
COOR'
COOR'
Ph3P
O
S
COOR'
R
O
S
COOR'
R
N
N
R
SiO2
°
N
N
R
90 C
(8)
(9)
O
O
R
N
O
N
N
S
R
COOR'
+
OR'
(11)
+
R'OH
(13)
S
C
N
O
R
R
(10)
R'OOC
(12)
R
N
12
R'
R
A
B
C
diisopropylamine
diisopropylamine
piperidine
CH3
CH3-CH2
CH3
D
piperidine
CH3-CH2
Scheme 1

CONVERSION OF STABILIZED PHOSPHORUS YLIDES
1923
secondary amines (2) to benzoyl isothiocyanate (1), with acetylenic ester (5) in the presence
of triphenylphosphine (4) proceed in CH2Cl2 at –5◦C to produce ylide (8). The TLC test
indicated formation of the ylide in CH2Cl2. Silica gel powder was found to catalyze the
conversion of ylide (8) to benzo[e][1,3]thiazocin derivatives (12) in solvent-free conditions
at 90◦C in fairly good yields.
The ylide (8) may result from the initial addition of triphenylphosphine (4) to the
acetylenic ester (5) and concomitant protonation of the 1:1 adduct, followed by the elec-
trophilic attack of the vinyltriphenylphosphonium cation to the anion of the benzoyl thiourea
derivatives (7). The silica gel was found to catalyze the conversion of ylides (8) to vinylated
compounds (9) in solvent-free conditions.
The neighboring group is an amine, containing nitrogen with unshared electrons, and
R
N
R
(
)
this amine
of compounds 9 helps to push out the alkoxy anion, in order to get the
intermediate ammonium ion. This intermediate undergoes nuclophilic attack by the phenyl
and yields the product 12. The TLC indicated that the reaction was completed in the presence
of silica gel at 1 h, but this reaction was completed at reflux temperature (CH2Cl2 as solvent)
after 120 h. In this reaction, we have used MgSO4, MgO, ZnO, ZnSO4, Al2O3, Al2(SO4)3,
NaHSO4, CuO, Cu(NO3)2 CuSO4, FeSO4, Mn(NO3)2, and MnO2 powder instead of silica
gel, but no corresponding product 12 was observed.
The structures were deduced from their melting points, IR, 1H NMR and 13C NMR
spectroscopy, and mass spectrometry.
CONCLUSION
In summary, we believe the reported method offers a mild, simple, and efficient route
for the preparation of benzo[e][1,3]thiazocin derivatives. Its ease of workup, high yield, and
fairly mild reaction conditions make it a useful addition to modern synthetic methodologies.
Other aspects of this process are under investigation.
EXPERIMENTAL
Starting materials and solvents were obtained from Merck (Germany) and Fluka
(Switzerland) and were used without further purification. TLC and NMR indicated that
there is no side product. Melting points were measured on an Electrothermal 9100 apparatus
1
and are uncorrected. IR spectra were measured on a Shimadzu IR-460 spectrometer. H
and 13C NMR spectra were measured (CDCl3 solution) with a Bruker DRX-300 AVANCE
spectrometer at 300.13 and 75.467 MHz, respectively. Elemental analyses were performed
using a Heraeus CHN-O-Rapid analyzer. Mass spectra were recorded on a Finnigan-MATT
8430 mass spectrometer operating at an ionization potential of 20 eV. Flash chromatography
columns were prepared from Merck silica gel powder.
General Procedure for the Preparation of Compounds 12a–d
To a solution of benzoyl isothiocyanate 1 (0.163 g, 1 mmol) and secondary amine 2
(1 mmol) in dry CH2Cl2 (5 mL) magnetically stirred for 2 h, triphenylphosphine 4 (0.262 g,
1 mmol) and finally a solution of acetylenic ester 5 (1mmol) dropwise in dry CH2Cl2 (3 mL)
was added at –5 was added C temperature over 10 min. The mixture was allowed to warm
to room temperature. Silica gel powder (2 g) was added, and the solvent was evaporated.
The dry materials were heated for 1 h at 90◦C and then placed over a column of silica gel

1924
A. SOULDOZI AND A. R. DADRASS
(10 g). The column chromatography was washed using ethyl acetate/light petroleum ether
(1:10) as an eluent. The solvent was removed under reduced pressure and the products were
obtained. The characterization data of the compounds (12a–d) are given below.
Selected Data for (E)-Methyl 2-((Z)-3-(Diisopropylamino)-1,6-
dioxo-1H-benzo[e][1,3]thiazocin-5(6H)-ylidene)acetate (12a)
White crystals; mp: 81.4–82.9◦C; Yield: 82%. IR (KBr)(vmax, cm−1): 3020, 2965,
1706 and 1258. 1H NMR (CDCl3) δH: 1.42 (12H, d, 3JHH = 6.9 Hz, CH3 of isopropyl), 3.74
(3H, s, OCH3), 3.92–3.96 (2H, m, CH of isopropyl), 7.27 (1H, s, CH of vinylic), 7.39–7.42
and 7.81–7.84 (4H, m, arom). 13C NMR (CDCl3) δC: 20.02 (4C, CH3 of isopropyl) 51.15
(1C, OCH3), 51.44 (2C, CH of isopropyl), 127.38, 128.78 and 129.95 (5C of CH), 128.86,
130.86 and 135.12 (4C), 160.65, 162.62 and 168.01 (3C of C O). MS: m/z (%); 374 (M+,
5), 318 (60), 275(100), 261(94), 229(19), 89(18), 43(32). Anal. Calcd. For C19H22N2O4S
(374.45): C 60.94, H 5.92, N 7.48. Found: C 60.81, H 5.79, N 7.41%.
Selected Data for (E)-Ethyl 2-((Z)-3-(Diisopropylamino)-1,6-
dioxo-1H-benzo[e][1,3]thiazocin-5(6H)-ylidene)acetate (12b)
Yellow crystals; mp: 94.0–95.1◦C; Yield: 79%. IR (KBr)(vmax, cm−1): 3031, 2966,
1700 and 1260. 1H NMR (CDCl3) δH: 1.26 (3H, t, 3JHH = 7.1 Hz, CH3 of Et); 1.42 (12, d,
3JHH = 7.0 Hz, CH3 of isopropyl); 3.91–3.95 (2H, m, CH of isopropyl); 4.21 (2H, q, 3JHH
=
7.1, CH2 of Et), 7.27 (1H, s, CH of vinylic); 7.38–7.41 and 7.80–7.84 (4H, m, arom). 13
C
NMR (CDCl3) δC: 14.34 (1C, CH3 of Et); 20.04 (4C, CH3 of isopropyl); 51.14 (1C, CH2 of
Et); 60.31 (2C, ch of isopropyl); 127.32, 128.68 and 129.99 (5C of CH); 128.79, 130.90
and 135.28 (4C), 159.76, 162.25 and 167.98 (3C of C O). MS: m/z (%); 388 (M+, 3), 332
(56), 289 (100), 244 (81), 160 (15), 101 (21), 77(25), 58 (31), 45 (28). Anal. Calcd. For
C20H24N2O4S (388.48): C 61.83, H 6.23, N 7.21. Found: C 61.75, H 6.15, N 7.19%.
Selected Data for (E)-Methyl 2-((Z)-1,6-Dioxo-3-(piperidin-1-yl)-
1H-benzo[e][1,3]thiazocin-5(6H)-ylidene)acetate (12c)
White crystals; mp: 99.5–100.6◦C; Yield: 75%. IR (KBr)(vmax, cm−1): 3015, 2997,
1
2962, 1715 and 1245. H NMR (CDCl3) δH: 1.68–1.72 (6H, m, CH2 of piperidine);
3.57–3.59 (4H, m, CH2 of piperidine); 3.74 (3H, s, OCH3); 7.27 (1H, s, CH of vinylic);
7.39–7.41 and 7.75 (4H, m, arom). 13C NMR (CDCl3) δC: 22.97, 23.76 and 49.17 (5C,
CH2); 51.53 (1C, OCH3); 127.54, 128.90 and 129.76 (5C of CH); 128.79, 130.86 and
134.90 (4C); 160.38, 162.44 and 170.90 (3C of C O). MS: m/z (%); 358 (M+, 3), 300
(100), 275(77), 167(18), 149 (40), 85 (21), 71 (19), 58 (47), 43 (95). Anal. Calcd. For
C18H18N2O4S (358.41): C 60.32, H 5.06, N 7.82. Found: C 60.27, H 4.98, N 7.75%.
Selected Data for (E)-Ethyl 2-((Z)-1,6-Dioxo-3-(piperidin-1-yl)-
1H-benzo[e][1,3]thiazocin-5(6H)-ylidene)acetate (12d)
Viscous oil; Yield: 71%. IR (KBr)(vmax, cm−1): 3027, 2936, 1708 and 1243. 1H NMR
(CDCl3) δH: 1.24 (3H, t, 3JHH = 7.1 Hz, CH3 of Et); 1.68–1.70 (6H, m, CH2 piperidine);
3.57–3.58 (4H,m, CH2 of piperidine); 4.20 (2H, q, 3JHH = 7.1 Hz, CH2 of Et); 7.27 (1H,
s, CH vinylic), 7.37–7.39 and 7.73–7.76 (4H, m, arom). 13C NMR (CDCl3) δC: 14.25 (1C,
CH3); 23.76, 23.99 and 49.17 (5C, CH2); 60.46 (1C, OCH2), 127.49, 128.82 and 129.79

CONVERSION OF STABILIZED PHOSPHORUS YLIDES
1925
(5C, CH); 127.83, 130.86 and 135.01 (4C); 159.99, 162.05 and 170.84 (3C of C O).
MS: m/z (%); 372 (M+, 4), 314 (100), 289 (71), 269 (20), 242 (10), 217 (8), 133 (38), 85
(18), 45 (21). Anal. Calcd. For C19H20N2O4S (372.44): C 61.27, H 5.41, N 7.52. Found: C
61.24, H 5.37, N 7.48%.
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