Application of the "fries like" rearrangement using ZnCL 2 for the synthesis of 6-acyl-2(3H)-benzothiazolones

Article abstract of DOI:10.1080/10426500307842

In this work we report another method of acylation on the 6-position of the 2(3H)-benzothiazolone ring with Fries-like rearrangement catalyzed by zinc chloride instead of aluminium chloride and 3-acyl-2(3H)-benzothiazolones derivatives as starting materia

Full text of DOI:10.1080/10426500307842

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Application of the "Fries Like" Rearrangement
Using ZnCl 2 for the Synthesis of 6-Acyl-2(3H)-
benzothiazolones
Faouzi Guenadil a & Hocine Aichaoui a
a Université Badji Mokhtar, Annaba, Algérie
Published online: 27 Oct 2010.
To cite this article: Faouzi Guenadil & Hocine Aichaoui (2003): Application of the "Fries Like" Rearrangement Using ZnCl 2 for
the Synthesis of 6-Acyl-2(3H)-benzothiazolones, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:8, 1703-1708
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Phosphorus, Sulfur, and Silicon, 178:1703–1708, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390200747
APPLICATION OF THE “FRIES LIKE”
REARRANGEMENT USING ZnCL2 FOR THE
SYNTHESIS OF 6-ACYL-2(3H)-BENZOTHIAZOLONES
Faouzi Guenadil and Hocine Aichaoui
Universite´ Badji Mokhtar, Annaba, Alge´rie
(Received August 8, 2002; accepted November 19, 2002)
In this work we report another method of acylation on the 6-position
of the 2(3H)-benzothiazolone ring with Fries-like rearrangement cat-
alyzed by zinc chloride instead of aluminium chloride and 3-acyl-2(3H)-
benzothiazolones derivatives as starting materials. This method is ad-
vantagous in regard to other acylation methods as it requires only
three equivalents of ZnCl2 to produce 6-acyl-derivatives with yields of
82–94%.
Keywords: 2(3H)-Benzothiazolone; 3-acyl-2(3H)-benzothiazolones;
6-acyl-2(3H)-benzothiazolones; Fries-like rearrangement; ZnCl2;
ZnCl2-DMF
It is known that the major problem in the use of Lewis acids in the
Friedl-Crafts acylation of electron-rich aromatic compounds is the com-
plexation of these substrates by Lewis acids. These substrates become
highly deactived in this electrophylic aromatic substitution.1 This prob-
lem can be alleviated to some extent by using the complex (AlCl3-DMF)
as a catalyst.2 This reagent was reported in a series of recent papers.3−6
The application of these conditions in the case of 2(3H)-benzothiazolone
was previously reported.7
Recently,8,9 the use of zinc chloride as a catalyst instead of aluminium
chloride in dimethylformamide as complexing agent,10 in the acylation
reaction of 2(3H)-benzothiazolone using activated forms of carboxylic
acids (acid halides or anhydrides), 6-acyl-2(3H)-benzothiazolones were
formed in satisfactory yields.9 The disadvantage of the use of these
complexes is the important consumption of AlCl3 and ZnCl2 necessary
to accomplish the reaction in high yields. The acylation in the present
case was found to proceed with satisfactory rate and yields only when
Address correspondence to Faouzi Guenadil, Laboratoire de Chimie Pharmaceu-
tique, Institut de Chimie, Universite´ Badji Mokhtar, BP-12, Annaba, Alge´rie. E-mail:
guendouda@yahoo.fr
1703

1704
F. Guenadil and H. Aichaoui
the ratio of AlCl3/substrate was in the range of 7–117 and in the range
of 8–109 in the case of ZnCl2/substrate ratio.
The alternative synthetic method which employs “Fries-like” rear-
rangement catalyzed by AlCl3 and 3-acyl-2(3H)-benzothiazolones as
starting materials, permits the preparation of 6-acyl-derivatives in high
yields11 (Scheme 1 method a). This method presented an advantage
with regard to other acylation methods.7,9,12 It requires only 2,5 equiv-
alents of AlCl3 to perform the reaction in good yields.11
6-Acyl-2(3H)-benzothiazolones derivatives have particularly inter-
esting anti-inflammatory, antiepileptic, antiviral, analgesic, and anti-
convulsant properties.11 In view of the interest of these compounds, an
optimization of their synthesis was performed.
In this work, the 6-acyl-2(3H)-benzothiazolones were obtained by
the use of Fries-like rearrangement with zinc chloride as a catalyst
instead of aluminium chloride and the 3-acyl-2(3H)-benzothiazolones
were the preferred starting materials for the synthesis of these deriva-
tives (Scheme 1, method b). This method yielded the 6-acyl derivatives
in high yield and excellent purity.
SCHEME 1
RESULTS AND DISCUSSION
According to the synthesis shown in Figure 1, 2(3H)-benzothiazolone
was used as starting material to prepare the tragect 6-acyl-2(3H)-
benzothiazolones with 3-acyl-(2H)-benzothiazolones as intermidiates.
The N-acylate reaction of 2(3H)-benzothiazolone was performed
by allowing it to interact with acid anhydrides in refluxing11 sol-
vent (Scheme 2, method c) or with acid halides in the presence of
FIGURE 1

Application of the “Fries Like” Rearrangement Using ZnCl2
1705
sodium ethylate in dimethyl sulfoxyde.13 In our work we have used
the dimethylformamide as solvent (Scheme 2, method d). This method
gave the corresponding 3-acyl-2(3H)-benzothiazolones (2a–f) in excel-
lent yields (Table I).
SCHEME 2
The migration of the acyl groupe from the N-position to the 6-position
of this heterocycle was also obtained by the reaction shown in Scheme 1,
method b.
Treatment of 3-acyl-2(3H)-benzothiazolones (2a–f) employing 3
equivalents of zinc chloride at the temperature of 155◦C, gave the de-
sired 6-acyl-2(3H)benzothiazolones in high yields in the range of (82–
94%) (Table I). The 6-acyl derivatives were the only products isolated
from the reaction medium. Their structures were confirmed by IR, 1H-
NMR spectroscopy, and elemental analysis. They were compatible with
the products obtained with AlCl3 and are in accordance with published
data.7,11,14
The mechanism of the rearrangement is intramolecular. The
investigation of this mechanism was previously study by reaction of
3-benzoyl-2(3H)-benzothiazolone in the presence of 2(3H)-benzo-
thiazolone.11 No product was detected under these conditions.
As already mentioned above, the major problem of the use of (ZnCl2-
DMF) reagent such as in the case of (AlCl3-DMF) is the important
TABLE I Yields of 3-Acyl-2(3H)-benzothiazolone (2a–f)
and 6-Acyl-2(3H)-benzothiazolone (3a–f) Derivatives
No.
R
Yields (%) No.
Yields (%) m.p. (◦C)
2a
2b
2c
2d
2e
2f
CH3
CH2CH3
C6H5
C6H4(Cl-p)
C6H4(NO2-p
C6H4(F-p)
97a
94a
98b
96b
97b
97b
3a
3b
3c
3d
3e
3f
87
82
94
86
84
85
190–191
203–205
216–217
275–277
254–265
235–237
aMethod c.
bMethod d.

1706
F. Guenadil and H. Aichaoui
TABLE II Comparative Yields of 6-Acyl-derivatives Obtained by
(ZnCl2-DMF) and Fries-like Methods
Condions of (Zncl2-DMF) method
Reaction Yields Fries-like
No.
R
ZnCl2 equi Temp (◦C)
time (h)
(%)
yield (%)
3a
3b
3c
3d
3e
3f
CH3
CH2CH3
C6H5
C6H4(Cl-p)
C6H4(NO2-p)
C6H4(F-p)
9
9
9
9
9
9
130
130
140
145
145
145
1,30
1,40
2
2
2
67
63
81
68
64
25
87
82
94
86
84
83
2
consumption of ZnCl2. The present method requires only 3 equivalents
of this catalyst to performed the reaction in good yields. To investigate
this method, we have caused to react 2(3H)-benzothiazolone with the
corresponding acid halides in the presence of the condition of Friedl-
Crafts using the complex (ZnCl2-DMF).11,12 However, under these con-
ditions, the yields (Table II) of the corresponding 6-acyl-derivatives
were lower than those of the present method. The comparative yields ob-
tained by the zinc chloride-N,N-dimethylformamide method and Fries-
like reaction using zinc chloride for similar compounds are summarized
in Table II.
CONCLUSION
The rearrangement of 3-acyl-2(3H)-benzothiazolones to the 6-position
of the heterocycle catalyzed by ZinCl2 appears to be parallel to that with
AlCl3. In Fries-like rearrangement, the 3-acyl-2(3H)-benzothiazolones
at the temperature of 155◦C in the presence of 3 equivalents of zinc
chloride as a catalyst gave the 6-acyl-2(3H)-benzothiazolones in high
yields (82–94%). The 6-acyl-derivatives can be obtained by the reac-
tion of 2(3H)-benzothiazolone with acid halides and the complex of
(ZnCl2-DMF). However, the yields in these conditions are lower than
that in the present method. From these results, it appears that this
method can be an alternative to the former acylation procedures of
2(3H)-benzothiazolone.
Experimental
Melting points were determined using an electrothermal melting point
apparatus and are uncorrected. The IR spectra were recorded on a

Application of the “Fries Like” Rearrangement Using ZnCl2
1707
spectrometer Shimadzu Chart 200-91538 and the 1H-NMR spectra
were recorded on a Bruker AC 250 spectrometer (250 MHz) us-
ing Me2SO-d6. Chemical shifts (δ) are reported in ppm with tetram-
ethylsilane as internal standard. Elemental analysis were performed
by the Ecole Nationale Supe´rieure de Chimie Montpellier. France.
The compounds were pure in T.L.C. (Merck silica gel. 60254. ethylac-
etate/cyclohexane, 3/2, v/v).
Procedures for the Synthesis of 3-Acyl-2(3H)-
benzothiazolones (2a---f)
Method C (2a–b). A solution of 2(3H)-benzothiazolone (0.0145 mmol)
in acetic or propionic anhydride (20 ml) was refluxed for 3 h. After
cooling, the resulting solution was evaporated in the vacuum and the
residue recrystallized from ethanol. The physical properties (mp, IR,
1H-NMR) are in accordance with published data.11
Method D (2c–f). To a solution of (0.015 mmol) 2(3H)-benzothiazolne
in 30 ml of dimethylformamide was added sodium ethylate
(0.017 mmol). Then added dropwise a solution of acid halides dissolved
in a minimum of dimethylformamide. The reaction mixture was heated
at the temperature of 75◦C under stirring during a period of 4 h. After
cooling, ice water was added and the muxture stirred for 1 h. Then fil-
tered and washed with a solution of 10% of (NaHCO3), finally washed
with water and dried. Recrystallized from ethanol. The following exam-
ples demonstrate the procedure.
3-(4-Chloro)-benzoyl-2(3H)-benzothiazolone (2d). m.p. 108–110◦C,
IR (KBr): 1660 cm−1, (C O. lactan), 1630 cm−1, (C O); 1H-NMR. (250
MHz, DMSO-D6): 7,29 (2H, m), 7,46 (3H, m), 7,60 (dd, 1H, J = 1,6, 8,4
Hz), 7,81 (2H, dd, J = 1,6, 8,4 Hz).
3-(4-Nitro)-benzoyl-2(3H)-benzothiazolone (2e). m.p. 160–161◦C, IR
(KBr): 1665 cm−1, (C O. lactan), 1630 cm−1, (C O); 1H-NMR.
(250 MHz, DMSO-D6): 7,40 (2H, m), 7,77 (1H, d, J = 8,6 Hz), 7,86 (1H,
d, J = 8,6 Hz), 8,10 (2H, d, J = 8,4 Hz), 8,30 (2H, m).
General Procedure for the Reaction of 3-Acyl-2(3H)-
benzothiazolones by Fries-like Rearrangement Using
Zinc Chloride
Zinc chloride (0.111 mmol, 15,127 g) and (0.037 mmol) of 3-acyl-
2(3H)-benzothiazolone (2a–f) were placed in a three necked round bot-
tom flask (100 ml) with a reflux condenser and a CaCl2 tube. The reac-
tion medium was heated for 3 h at 155◦C under stirring. After cooling,

1708
F. Guenadil and H. Aichaoui
the dark complex was decomposed by addition of water and 2 ml of 1N
HCl. The resulting precipitate was stirred for 30 min, filtered, washed
with water, dried, and recrystallized from ethanol. The following exam-
ples demonstrate the procedure.
6-Acetyl-2(3H)-benzothiazolone (3a). IR (KBr): 3160 cm−1 (NH),
1700 cm−1, (C O. lactan), 1660 cm−1, (C O); 1H-NMR. (250 MHz,
DMSO-D6): 2.57 (3H, s), 719 (1H, d, J = 8.4 Hz), 7.88 (1H, dd, J =
1,6, 8,4 Hz), 8,23 (1H, d, J = 1,6 Hz), 12.18 (1H, s, broad). Anal: Calcul:
C, 55,94, H, 3,64, N, 7.25. Found: C, 55,76, H, 3,64, N, 7,28.
6-Benzoyl-2(3H)-benzothiazolone (3c). IR (KBr, ν cm−1); 3220 cm−1
,
1
(NH), 1680 cm−1, 1630 cm−1, (C O); H-NMR (250 MHz, DMSO-D6):
7,23 (d, 1H, J = 8,4 Hz), 7,58 (m, 6H), 8,00 (d, 1H, J = 1,6 Hz), 12 (s,
1H, NH). Anal: Calcul: C, 65,87, H, 3,54, N, 5,48. Found: C, 65,69, H,
3,60, N, 5,39.
6-(4-Chloro)-benzoyl-2(3H)-benzothiazolone (3d). IR (KBr, ν cm−1);
3160 cm−1, ( NH), 1680 cm−1, 1630 cm−1, (C O); 1H-NMR (250 MHz,
DMSO-D6): 7,24 (d, 1H, J = 8,4 Hz), 7,58 (m, 2H), 7,68 (dd, 1H, J = 1,6
Hz), 7,74 (m, 2H), 8,01 (d, 1H, J = 1,6 Hz), 12 (s, 1H, NH). Anal: Calcul:
C, 58,03, H, 2,78, N, 4,83. Found: C, 57,84, H, 2,81, N, 4,99.
REFERENCES
[1] Y. Shen, H. Liu, and Y. Chem, J. Org. Chem., 55, 3961 (1990).
[2] H. Aichaoui, J. H. Poupaert, D. Lesieur, and J. P. He´nichart, J. Heterocyclic. Chem.,
29, 171 (1992).
[3] H. Aichaoui, J. H. Poupaert, D. Lesieur, and J. P. He´nichart, Tetrahedron, 47, 6649
(1991).
[4] H. Aichaoui, J. H. Poupaert, D. Lesieur, and J. P. He´nichart, Bull. Soc. Chim. Belg.,
101, 1053 (1992).
[5] J. H. Poupaert, M. Kanyonyo, H. Ucar, et al., Bull. Soc. Chim. Belg., 105, 397 (1996).
[6] H. Ucar, K. Van Depoorten, M. Kanyonyo, et al., Bull. Soc. Chim. Belg., 105, 773
(1996).
[7] S. Yous, J. H. Poupaert, I. Lesieur, P. Depreux, and D. Lesieur, J. Org. Chem., 59,
1574 (1994).
[8] F. Guenadil, H. Aichaoui, and M. Liacha, Phosphorus, Sulfur, and Silicon, 177, 1
(2002).
[9] F. Guenadil and H. Aichaoui, Phosphorus, Sulfur, and Silicon, in press (2002).
[10] M. Liacha, S. Yous, J. H. Poupaert, et al., Mont. Fu¨r. Chem., 130, 1393 (1999).
[11] H. Ucar, K. Van Depoorten, P. Depovere, et al., Tetrahedron, 54, 1763 (1998).
[12] J. P. Bonte, D. Lesieur, C. Lespagnol, et al., Eur. J. Med. Chem., 9, 491 (1974).
[13] Z. Moussavi, D. Lesieur, C. Lespagnol, J. Sauzieres, and Ph. Olivier, Eur. J. Med.
Chem., 24, 55 (1989).
[14] H. Ucar, K. Van Derpoorten, M. Kanonyo, et al., Bull. Soc. Chim. Belg., 105, 773
(1996).