Ionic liquid-accelerated N-arylation of 5-arylidene-2,4-thiazolidinediones with diaryliodonium salts

Article abstract of DOI:10.3184/030823408X382144

An efficient method for the synthesis of N-aryl-5-arylidene-2,4- thiazolidinediones has been developed involving the N-arylation of 5-arylidene-2,4-thiazolidinediones derivatives with diaryliodonium salts in the ionic liquid [bmim]PF₆ (1-butyl-

Full text of DOI:10.3184/030823408X382144

686 RESEARCH PAPER
DECEMBER, 686-687
JOURNAL OF CHEMICAL RESEARCH 2008
Ionic liquid-accelerated N-arylation of 5-arylidene-2,4-thiazolidinediones
with diaryliodonium salts
De-Hong Yanga*, Hong-Liang Gaoa, Ben-Yang Yanga and Zhen-Chu Chenb
aDepartment of Materials and Chemistry, Zhongyuan University of Technology, Zhengzhou, 450007, P.R. China
bDepartment of Chemistry, Zhejiang University, Hangzhou, 310028, P.R. China
An efficient method for the synthesis of N-aryl-5-arylidene-2,4-thiazolidinediones
N-arylation of 5-arylidene-2,4-thiazolidinediones derivatives with diaryliodonium
(1-butyl-3-methyl im idazol iu m hexafl uorophosphate).
has been developed involving the
salts in the ionic liquid [bmim]pF6
Keywords: ionic liquid, N-arylation, 2,4-thiazolidinediones derivatives, diaryliodonium salts
Thiazolidinone derivatives are
a bio-active group of
0
0
heterocyclic compounds.1,2 They have again attracted interest
because of their antidiabetic activities and pioglitazone
and rosiglitazone have been launched for type 2 diabetes
mellitus.3,4 The common method of synthesising N-aryl-
thiazolidinedione moieties utilised the condensation of
chloroacetic acid with the aryl-substituted thiourea followed
by acid hydrolysis. Another method utilised the reaction of
aryl isocyanates with ethyl thioglycolate in the presence of
sodium metal. 5 These preparations are unsatisfactory because
of their long time reaction, harmful solvents and low yields.
The applications of hypervalent iodine compounds in
organic synthesis are interesting.6,7 Recently we showed
that diaryliodonium salts are efficient electrophilic arylating
reagents, and ionic liquids can accelerate the arylation reactions
rates of the diaryliodonium salts.s Relative to conventional
molecular solvents, ionic liquids have many advantages.9,10
We considered that the preparation of N-aryl-5-arylidene-
2,4-thiazolidinediones in ionic liquids, coupled with the high
electrophilic reactivity of diaryliodonium salts, would be
useful.
KOH
+
Ph21BF4
•
+
Phi
r
N-H
r
N-Ph
[bmim]PF6
8-4
8-4
0
0
1a
2
3a
Scheme
1
Table
1
Reactions of 2.4-thiazolidinedione
(1a) with diphenyl-
iodonium salts (2) to form 3-phenyl-2.4-thiazolidinedione
different solvents in the presence of KOH
(3a) in
Entrya
Yield/%b
Solvent
Time/h
TemprC
1
2
3
4
5
DMF
CH3CN
[bmimlPF6
[bmimlBF4
[bpylBF4
Reflux
Reflux
80
12
12
2
6
6
46
39
80
72
60
80
80
aA11reactions were run with 2.4-thiazolidinedione
and diphenyliodonium
(1a, 0.5 mmol)
salts (2, 0.55 mmol) in solvents (5 ml)
in the presence of KOH (0.5 mmol).
blsolated yields based on 2.4-thiazolidinedione
(1a).
First, we examined the efficiency of different solvents for the
N-phenylation of2,4-thiazolidinedione with diphenyliodonium
in the presence ofKOH (see Scheme 1).The results, summarised
in Table 1, show that the ionic liquid [bmim]PF6 gave the
best results in terms of yields and reaction times. As can be
seen from Table 1, the ionic liquids compared with classical
molecular solvents, have the advantages of accelerating rate
and increasing yield. For example, the preparation of N-
phenyl-2,4-thiazolidinedione (3a) needed refluxing for 12 long
hours in the classical molecular solvents dimethylformamide
or acetonitrile. Yet, the same reaction was successful in ionic
liquid [bmim]PF6 at only 80°C within 2 h, and gave higher
yield (80%). Furthermore, the tempemture of the reaction
in the ionic liquid, 80°C, is lower than that using the solvent
dimethylformamide (b.p. 158°C), and is approximately
equivalent to that using acetonitrile (b.p. 81°C).
Table 2 Results obtained using recycled ionic liquid
Entrya
Yield/%b
Product
Cycle
1
2
3
3a
3a
3a
3a
1
2
3
80
78
80
81
4
4
aA11reactions were run with 2.4-thiazolidinedione
0.078 g) and diphenyliodonium tetrafluoroborate
0.202 g) in [bmimlPF6 (5 ml) in the presence of KOH (0.5 mmol)
at 80°C for 2 h.
(0.5 mmol,
(0.55 mmol,
blsolated yields based on 2.4-thiazolidinedione.
also proceeded successfully for the substituted (Ar' = 4-CHr
Ph, 4-CH30-Ph) diaryliodonium tetrafluoroborates without
variation in the yield. All the products were characterised by
IH NMR, JR, and the melting points which were consistent
with the litemture datall-B . Elemental analyses for the new
compound also matches the calculated value.
The ionic liquid can be typically recovered by extracting
the product, and then washing with water followed by vacuum
drying. No obvious decrease of yields was observed while
reusing the recovered solvent. The results are summarised in
Table 2.
As shown in Schemes 1 and 2, the iodoarene was another
We investigated the reactions of 5-arylidene-2,4-
thiazolidinediones (1) with diaryliodonium tetrafluoroborate (2)
at 80°C in the ionic liquid [bmim]PF6 in the presence ofKOH
(see Scheme 2). The results summarised in Table 3, show that
5-arylidene-2,4-thiazolidinediones (Ar = 4-CHrPh, 4-CH30-
Ph, 3,4-(CH30)rPh, 4-NOrPh, Ph, Ph-CH=CH, 2-furyl)
reacted smoothly with diphenyliodonium tetrafluoroborates and
gave adequate yields (50%-85%) after 2-4 h at 80°C in the
ionic liquid [bmim]PF6 in the presence ofKOH. The reactions
product as well as the N-aryl-2,4-thiazolidinediones
in
the reaction. It could be converted easily to the respective
diaryliodonium salts in adequate yields as described in our
previous work.14
In conclusion, an efficient, clean, and novel method for
the synthesis of N-aryl-5-arylidene-2,4-thiazolidinediones
has been developed using a non toxic arylation agent
(diaryliodonium salts) which can be regenerated in adequate
yield to replace aryl halides. Employment of ionic liquid
rather than classical molecular solvents leads to mild reaction
conditions. The ionic liquid can be recycled.
* Correspondent. E-mail: janeydh@hotmail.com

JOURNAL OF CHEMICAL RESEARCH 2008 687
o
o
+
ArCH~N-H
+
ArCH~N-Ar'
Ar'l
s-4
s-4
o
o
1
2
3
3b. Ar=Ph, Ar'=Ph; 3c. Ar=4-CH.3-Ph,Ar'=Ph;3d. Ar=4-CH30-Ph, Ar'=Ph;
3e. Ar=3,4-(CH30h-Ph, Ar'=Ph; 3f. Ar=4-N~-Ph, Ar'=Ph; 39. Ar=Cinnamyl, Ar'=Ph;
3h. Ar=Furfuryl,Ar'=Ph; 3i. Ar=Ph, Ar'=4-CH.3-Ph;3j. Ar=Ph, Ar'=4-CH30-Ph
Scheme
2
3-Phenyl-5-(3, 4-dimethoxybenzylidene)-2, 4-thiazolidinedione
(3e):
Table
with diaryliodonium
arylidene-2.4-thiazolidinediones
3
Reactions of 5-arylidene-2.4-thiazolidinediones
(1)
M.p. 209-210 C, lit.12 208-209°C; IR 3124, 3040, 2895, 2799,
0
tetrafluoroborate
(2) to form 3-aryl-5-
(3)a
Ar'
1735, 1690, 1510, 1155, 1279 cm·I; IH NMR 3.81-3.83 (6H, s,
OCH3 ), 7.26-7.29 (3H, ill, ArH), 7.35-7.38 (5H, m, ArH), 7.91 (lH,
s, CH=).
Product(3)
Ar
Time/h
Yield/%b
3-Phenyl-5-(4-nitrobenzylidene)-2,4-thiazolidinedione
(31): M.p.
3b
3c
3d
3e
3f
39
3h
3i
Ph
Ph
Ph
Ph
Ph
Ph
2
2
3
4
3
3
2
3
3
83
85
78
69
74
75
50
70
71
238-240°C, lit.12 239°C; IR 3210, 1711, 1688, 1612 cm·I; IH NMR
7.40-7.42 (5H, m, ArH), 7.80 (2H, d, J= 8 Hz, ArH), 8.12 (lH, s,
CH=), 8.34 (2H, d,J= 8 Hz,ArH).
4-CHr Ph
4-CH30-Ph
3.4-(CH30h-Ph
4-N02-Ph
Ph-CH=CH
2-Furyl
3-Phenyl-5-cinnamylidene-2,4-thiazolidinedione
(3g): M.p. 211-
213°C, lit.12 212-213°C; IR 3198, 3034, 1720, 1686, 1620, 1318,
1140,690 cm·I; IH NMR 6.98 (lH, t, J= 11.6 Hz, CH=CH'-CH=),
7.70 (2H, d, J = 11.6 Hz, CH' =CH-CH'=), 7.34-7.50 (lOH,
m,ArH).
Ph
Ph
Ph
Ph
4-CHr Ph
4-CH30-Ph
3j
3-Phenyl-5-fuifurylidene-2,4-thiazolidinedione
(3h): M.p. 217-
aA11reactions were run with 5-arylidene-2.4-thiazolidinediones
219°C, lit.12 218-219°C; IR 3140, 3035, 2814, 1730, 1689, 1613,
1338, 1032 cm·I; IH NMR 6.80 (lH, t, J = 6 Hz, 3-furyl-H), 7.16
(lH, d, J= 6 Hz, 4-furyl-H), 7.45-7.53(5H, m, ArH), 7.73 (lH, d,
J = 6 Hz, 5-furyl-H), 8.08 (lH, s, CH=).
(1,0.5 mmol)with diaryliodon iumtetrafluroborates
in ionic liquid [bmimlPF6 (5 ml) in the presence of KOH (0.5
mmol) at 80°C.
(2,0.6 mmol)
blsolated yields based on 5-arylidene-2.4-thiazolidinedione
(1).
3-(4-Methylphenyl)-5-benzylidene-2,4-thiazolidinedione
(3i): M.p.
202-204°C, lit.13 201°C; IR 3034, 2977, 1750, 1693, 1620, 1353,
1192 cm·I; IH NMR 2.39 (3H, s, CH3 ), 7.37-7.40 (4H, ill, ArH),
7.43-7.45(5H, ill, ArH), 8.00 (lH, s, CH=).
Experimental
Melting points were uncorrected. IR spectra were recorded as KBr
pellets on VECTOR-22 IR spectrophotometer. IH NMR spectra were
recorded on Broker (400 MHz) spectrometer using TMS and d6-
DMSO as an internal standard and solvent. Elemental analysis was
performed on Carlo Erba EA 1106 instrument.
3-(4-Methoxylphenyl)-5-benzylidene-2,4-thiazolidinedione
(3j):
M.p. 193-194°C; IR 3047, 2981,1755,1697,1614, 1364, 1150 cm·I;
IH NMR 3.79, (3H, s, OCH3 ), 7.40-7.42 (4H, ill, ArH), 7.57-7.58
(5H, m, ArH), 8.00 (lH, s, CH=). Anal. Calcd for C17H13N03S
C 65.58, H 4.28, N 4.50; Found C 65.40, H 4.51, N 4.46%.
3-Phenyl-2,4-thiazolidinedione (3a): typical procedure
2,4- Thiazolididione(O.5 mmol, 0.078 g) and diphenyliodonium
tetrafluoroborate (0.55 mmol, 0.202 g) were added to [bmim]PF6
(5 ml) in presence ofKOH (0.5 mmol, 0.028 g).The resulting mixture
was stirred at 80°C for 2 h. Then the reaction mixture was extracted
with Et20 (4 x 15 ml). The remaining ionic liquid suspension was
washed with water, and reused after drying in vacuum. The combined
ether solution was evaporated under reduced pressure. The crude
product was purified by preparative TLC (EtOAC-n-Hexane, 1: 2)
to give the product 3a (0.077 g, 80%) as a pale yellow solid.
3-Phenyl-2,4-thiazolidinedione(3a): M.p. 137-139°C, lit.l l 135°C;
IR 2978, 1758, 1697, 1673, 1366, 1152; IH NMR 7.47-7.56 (5H,
m, ArH), 4.16 (2H, s, CH2).
Received 15August 2008; accepted 13 October 2008
Paper 08/5180 doi: 10.3184/030823408X382144
Published online: 10 December 2008
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