Reaction of 2-phenyl-4-(ethoxymethylene)-5(4H)-oxazolone with 3,4-dithio-toluene in the presence of Lewis base

Article abstract of DOI:10.1080/10426500214888

A convenient procedure for the synthesis of thiocoumarin by the condensation of 2-phenyl-4-(ethoxymethylene)-5-(4H)-oxazolone with 3,4-dithio-toluene in the presence of triethylamine is reported. Here, both thio groups are able to react with the carbonyl group to produce a mixture of isomeric products at ambient temperature. Only one of the isomers upon heating gives a new coumarin product.

Full text of DOI:10.1080/10426500214888

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Phosphorus, Sulfur, and Silicon and the Related
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Reaction of 2-Phenyl-4-(ethoxymethylene)-5(4H)-
oxazolone with 3,4-Dithio-toluene in the Presence of
Lewis Base
Ahmad Momeni Tikdari a , Hooshang Hamidian a & Saeid Razee a
a Shahid Bahonar University of Kerman , Kerman, Iran
Published online: 27 Oct 2010.
To cite this article: Ahmad Momeni Tikdari , Hooshang Hamidian & Saeid Razee (2002) Reaction of 2-Phenyl-4-
(ethoxymethylene)-5(4H)-oxazolone with 3,4-Dithio-toluene in the Presence of Lewis Base, Phosphorus, Sulfur, and Silicon and
the Related Elements, 177:12, 2821-2826, DOI: 10.1080/10426500214888
To link to this article: http://dx.doi.org/10.1080/10426500214888
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2821–2826
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DOI: 10.1080/10426500290146857
REACTION OF 2-PHENYL-4-(ETHOXYMETHYLENE)-
5(4H)-OXAZOLONE WITH 3,4-DITHIO-TOLUENE
IN THE PRESENCE OF LEWIS BASE
Ahmad Momeni Tikdari, Hooshang Hamidian, and Saeid Razee
Shahid Bahonar University of Kerman, Kerman, Iran
(Received March 26, 2002; accepted May 10, 2002)
A convenient procedure for the synthesis of thiocoumarin by the con-
densation of 2-phenyl-4-(ethoxymethylene)-5-(4H)-oxazolone with 3,4-
dithio-toluene in the presence of triethylamine is reported. Here, both
thio groups are able to react with the carbonyl group to produce a mix-
ture of isomeric products at ambient temperature. Only one of the iso-
mers upon heating gives a new coumarin product.
Keywords: 3,4-Dithio-toluene; 5(4H)-oxazolone; electrophoresis; NMR
spectroscopy; thiocoumarin
5(4H)-Oxazolones have emerged as an important class of synthons.
2-Phenyl-4-(ethyoxymethylene)-5(4H)-oxazolone is one of the 5(4H)-
oxazolone derivatives with biological activity.1 It has been reported that
an ethoxy group attached to the ring can be displaced by various nucle-
ophilie reagents. Thus, this compound can be utilized as a synthone to
4
synthesize other derivatives which contain sulfur, and nitrogen.2
We now report new reactions of 2-phenyl-4-(ethoxymethylene)-
5(4H)-oxazolone, which are not nucleophilic substitution reactions and
where the ethoxy group is not displaced. It also should be noted that
after a short period some Fungi was observed on the crude compounds.
When 2-phenyl-4-(ethoxymethylene)-5(4H)-oxazolone is mixed with
3,4-dithio-toluene in the presence of triethylamine at room tempera-
ture, the carbonyl group of the oxazolone ring is attacked and the ring
is cleaved. Both thio groups (meta and para) are able to attack the car-
bonyl group, and therefore we have isomeric products but the group of
para is more reactive than the meta group.
Address correspondence to Ahmad Momeni Tikdari, Department of Chemistry, Shahid
Bahonar University of Kerman, Kerman 76175-133, Iran. E-mail: amt@yahoo.com
2821

2822
A. M. Tikdari et al.
SCHEME 1
These isomeric products could not be separated with ordinary meth-
ods. Therefore the isomeric products were determined with capillary
electrophoresis technique.
Solution of isomeric pairs were prepared by dissolving the crys-
4
taline powder at 10 M carrier electrolyte. Cyclodextrin-modified mi-
cellar electrokinetic chromatography (CD-MEKC) is a powerful sepa-
ration technique for the resolution of enantiomeric mixtrures as well
as isomeric paris (1, 2).5,6 In this technique inclusion complexation
of CDs with different stability constants can be utilized for enantio-
separation and resolution of isomeric pairs. To look for another evi-
dence for the formation of isomeric pairs of 1 and 2 in the reaction of
2-phenyl-4(ethoxymethylene)-5(4H)-oxazolone with 3,4-dithio-toluene
a mixture of reaction products was injected into the CD-MEKC sys-
tem in the presence and absence of ∝-CD in the carrier electrolyte
and the results were compared. When ∝-CD was not included in
the carrier electrolyte, electropherogram A in Figure 1 was obtained
which shows the disability of MEKC for the separation of isomeric
paris. Then 10 Mm ∝-CD was added to the carrier electrolyte, and
the obtained electropherogam B is also shown in Figure 1. Two dis-
tinct differences can be seen between electropherogams A and B. First
the reduction of migration time in the presence of ∝-CD due to iso-
meric complexation with ∝-CD and consequent increase of their ap-
parent mobilities which caused their faster elution. This phenomenon
is common and was reported before.7 Second the resolution of iso-
meric pairs is achieved which is a consequence of different stabili-
ties of complexes formed between ∝-CD and isomers. The first peak
was tentatively identified as isomer 2 and second one as isomer 1.
The percent of 2 and 1 isomers was calculated using the area of each
peak and found to be 71.82% and 28.18% respectively. These relative
1
amounts are in good agreement with the results obtained by HNMR
studies.
When a mixture of 2-phenyl-4-(ethoxymethylene)-5(4H)-oxazolone
and 3,4-dithio-toluene in the presence of triethylamin was heated in

Reaction of 2-Phenyl-4-(ethoxymethylene)-5(4H)-oxazolone
2823
SCHEME 2
dry benzene the products were found to be isomer 2 and (5-methyl-8-
thio-benzo)-4-ethoxy-thiopyrene-2-one (thiocoumarin) (Scheme 2).
Isomer 1 reacts intramolecularly and looses a bezoamido group. How-
ever, heat may cause 3,4-dithio-toluene dimerization.
If a mixture of isomeric pairs (1, 2) in the presence of triethylamin
was heated in dry n-hexan, isomer 2 does not react but isomer 1 reacts
FIGURE 1 Effect of ∝-CD complexation on peak resolution of isomeric pairs.
(A) without ∝-CD; (B) with ∝-CD peak 1: isomer 2 and peak 2: isomer 1.

2824
A. M. Tikdari et al.
intramolecularly and produces (5-methyl-8-thio-benzo)-4-ethoxy-thio-
pyrene-2-one (thiocoumarin) (Scheme 3).
SCHEME 3
EXPERIMENTAL
Melting points were determined on a Gallenkamp melting point appa-
ratus and are uncorrected. Mass spectra were obtained on a Shimadzu
QP1100 EX mass spectrometer, and IR spectra were recorded with a
Matson 1000 FT-IR spectrophotometer. Nuclear magnetic resonance
spectra were recorded on a Bruker DRX-500 Avance spectrometer using
tetramethylsilane as an internal standard.
A Jasco model CE-800 capillary electrophoresis system (Jasco/Tokyo/
Japan, consists of Jasco 890-CE high voltage power supply and a Jasco
875-CE intelligent UV-Vis detector) was used in this study.
Electropherograms were processed and recorded on a chromatopac
model CR3A instrument (Shimadzu/Japan).
Separation was performed at 20 KV which produced a current of
17 A. The detection of the separated peaks, was performed at 254 nm.
Separation was done using a fused-silica capillary tube (60 cm long.
50 m I.D. and 375 m O.D.) 48 cm to the detector.
Capillaries were obtained from GL scinces (Tokyo/Japan).
Buffer electrolyte consisted of disodium hydrogen phosphate ad-
justed to pH = 10, 50 mM sodium dodecyl sulfate (SDS), and 10 mM
-cyclodextrin (∝-CD).
Hydrodynamic injection was performed by raising the anodic end of
the capillary 5 cm higher than the level of cathodic vial for 15 s.
2-Phenyl-4-(ethoxymethylene)-5(4H)-oxazolone
A mixture of hippuric acid (18 g, 0.1 mmol), triethylorthoformate (14 g,
0.094 mmol) and acetic anhydride (20 ml, 0.21 mmol) was heated at

Reaction of 2-Phenyl-4-(ethoxymethylene)-5(4H)-oxazolone
2825
140 C for 1 h. The solvents removed in vacuo, the residue dissolved
in 25 ml of alcohol, cooled, filtered, and the residue washed with cold
petroleum ether to give 70% of product, m.p. 100–101 C, IR(KBr);
2980 (w, aliphatic), 1783 (s, C O), 1672 (s, N C) cm 1. Anal. Calcd
C12H11NO3C, 66.35%; H, 5.06% N, 6. 45%; Found C, 66.17%; H, 5.10%;
N, 6.43%.
1H NMR (CDCl3), H: 8.2 (m, 2H, ortho ArH), 7.5 (m, 3H, meta and
par a ArH), 7.35 (s, 1H, vinyl H), 4.5 (q, 2H, CH2O), 1.5 (t, 3H, CH3).
(2-Mercapto-4-methyl-phenyl)-2-benzamido-3-ethoxy-
thiopropenoate and (2-Mercapto-5-methyl-phenyl)-
2-benzamido-3-ethoxy-thiopropenoate
To a solution of 0.434 g (2 mmol) of 2-phenyl-4-(ethoxymethylene)-
5(4H)-oxazolone in 50 ml of dry benzene was added 0.312 g (2 mmol) of
3,4-dithio-toluene and 0.2 ml of triethylamine. The mixture was stirred
for 3 h at room temperature, then filtered and washed with dry ben-
zene. The residue was recrystallized from ethanol 96%, giving 0.47 g of
white crystals (yield 64%), m.p. 210 C.
IR (KBr) max: 1638 (CO), 1689 (CO), 3336 (NH) cm 1. Anal. Calcd
C19H19NO3S2 C, 61.12%; H, 5.09%; N, 3.60%; Found C, 60.89%; H,
1
5.08%; N, 3.66%. H NMR (CDCl3)
H 1.2 (t, 3H, CH3), 2.4 (s, 3H,
H
CH3), 3.5 (q, 2H, CH2), 3.9 (m, 1H, SHpara), 4.8 (m, 1H, NH) 5.2
(m, 1H, SH mata), 6.9 (s, 1H, C CH), 7.2–7.7 (m, 8H, ArH) ppm.
13C NMR: (CDCl3): 14.6, 21, 1, 59.4, 59.6, 64, 89.4, 127–141, 166.6,
1983 ppm.
(5-Methyl-8-thio-benzo)-4-ethoxy-thiopyrene-
2-one (Thiocoumarin)
To a solution of 0.434 g (2 mmol) of 2-phenyl-4-(ethoxy methylene)-
5(4H)-oxazolone in 50 ml of dry benzene was added 0.468 g (3 mmol) of
3,4-dithio-toluene and 0.5 ml of triethylamine.
The mixture was stirred and heated for 12 h. Then the precipitate
was filtered. The crude product was dissolved in hot ethanol and filtered
while it was hot, and kept at room temperature; it got pinkish and fungi
grew on the compound. The product decomposed at 160–165 C.
1
IR (KBr) max: 1688 (C O), 2962 (C C H) cm 1. H NMR (CDCl3)
H: 1.2 (t, 3H, CH3), 2.1–2.4 (brs, 4H, CH3, SH), 3.7 (q, 2H, CH2), 6.9
(s, 1H, Hvinyl), 7.3 (m, 2H, ArH) ppm. Anal Calcd. Calcd C12H12O2S2
C, 57.14%; H, 4.76%; S, 25.39%; Found C, 57.00%, H, 5.20%; S, 25.50%.
13C NMR (CDCl3): 18.37, 21.2, 58.3, 127.2–139.3 ppm. m/z 252 (M+,
37%), 122 (20%), 154 (30%), 105 (100%).

2826
A. M. Tikdari et al.
Dimer of 3,4-Dithio-toluene
When 3,4-dithio-toluene is taken in excess in of the conditions given
above, some of it dimers m.p. 50–51 C, were obtained. 1H NMR (CDCl3)
H: 2.2 (s, 6H, CH3), 7.2–7.4 (m, 6H, Arh) ppm. 13C NMR (CDCl3): 2.10,
127.2–139.3 ppm. m/z 308 (M+, 40%), 154 (100%), 122 (67%). Anal.
Calcd C14H12S4 C, 54.54%; H, 3.89%; N, 0.0%. Found: C, 53.82%; H,
4.01%; N, 0.0%.
REFERENCES
[1] P. L. Coleman, S. D. Milbrath, and M. M. Walker, PCT Int. Appl., 609, 436 (1992).
[2] A. M. Tikdari, P. K. Tripathy, and A. K. Mukerjee, Chem. Ind., 23, 825 (1986).
[3] A. K. Mukerjee, L. Homami, and S. S. Joseph, Can. J. Chem., 72, 1383 (1994).
[4] G. Just, B. Y. Chuny, S. Kim, G. Rosebery, and P. Rossy, Can. J. Chem., 54, 2089
(1976).
[5] H. Nishi, T. Fukayama, and S. Teralse, J. Chromatogr., 553, 503 (1991).
[6] H. Nishi and M. Matsuo, J. Liq. Chromatogr., 14, 973 (1991).
[7] S. Razee, A. Tamura, and T. Masujima, J. Chromatogr., 715, 179 (1995).
[8] E. N. Sukhomazova, E. N. Deryagina, and M. G. Voronkov, Zh. Org. Khim., 2, 405
(1980).