J. Chem. Sci. Vol. 124, No. 5, September 2012, pp. 1063–1069.


c Indian Academy of Sciences.

Heterocyclyl linked anilines and benzaldehydes as precursors

for biologically significant new chemical entities

RAMAN K VERMAa,∗, VIJAY KUMARa , PRITHWISH GHOSHa and LALIT K WADHWAb

a
Synthetic Organic and Medicinal Chemistry Laboratory, Department of Chemistry, Punjabi University,
Patiala 147 002, India
b
Ind-Swift Laboratories Limited (Research and Development Centre), Plot No. E-5, Industrial Area, Phase-2,
SAS Nagar, Mohali 160 055, India
e-mail: [email protected]

MS received 28 November 2011; revised 25 February 2012; accepted 8 March 2012

Abstract. Benzylidene and benzyl thiazolidinediones, oxazolidinediones, isoxazolidinediones and their

acyclic analogs like alpha alkylthio/alkoxy phenylpropanoic acids, beta-keto esters and tyrosine-based com-
pounds possess broad therapeutic potential in general and as Peroxisome Proliferator Activated Receptors
(PPARs) agonists in particular in the management of hyperglycemia and hyperlipidaemia for the treatment of
Type 2 Diabetes (T2D). We have synthesised and characterized some novel and suitably substituted hetero-
cyclyl linked benzaldehydes and anilines, which can be easily and very readily derivatized to all the above
mentioned classes to generate new chemical entities of broader biological significance. Synthesis of their
benzylidene thiazolidinedione and diethyl malonate and also benzyl diethyl malonate and alpha-bromoesters
derivatives is reported in some of the cases in the present work.

Keywords. Benzimidazole; indole; acridone; benzaldehyde; aniline.

1. Introduction in drug discovery research. The compounds containing

acridone structural unit may act potentially as antiher-
It is well-documented in the literature that benzim- pesvirus agents, 12 antitumour agents, 13 NS3 helicase
idazole, indole and acridone scaffolds are important inhibitor (that inhibits hepatitis C virus replication), 14
structural core in medicinal chemistry because their antimalarial agents. 15
derivatives exhibit illustrious biological and pharma- Aldehyde and amino, the two important func-
cological activities. The synthesis of benzimidazole tional groups, are of versatile utility in the field of
derivatives has gained importance during recent years organic synthesis. A medicinally significant library of
because of their broad spectrum of activities as antivi- numerous compounds, which may prove to be potent
ral, 1 antitumour, 2 antioxidant, 3 anticoagulant, 4 antihy- pharmacological agents, can be prepared starting
pertensive 5 and antiparasitic agents. 6 from substituted benzaldehydes and aminobenzenes.
Indole nucleus is another heterocyclic pharma- Pharmacologically active 2,4-thiazolidinediones, 16
cophoric component of immense medicinal signifi- oxazolidinediones, 17 isoxazolidine-3,5-dione, 18 1,3-di-
cance. Suitably substituted or fused indole ring carbonyls, 18 (1,3-diacids, 1,3-diesters, 1,3-diamides), 18
containing compounds demonstrate antiproliferative and α-alkoxy carboxylic acids 19,20 (figure 1) have
activity in many types of human cancer cells, 7 agonism been prepared from variously heterocyclyl linked
to cannabinoid receptors, 8 antitumour activity, 9 free benzaldehydes. Similarly, there are reports of phar-
radical scavenging activity, 10,11 anti-inflammatory acti- macologically active 2,4-thiazolidinediones 21,22 and
vity. 11 Similarly, acridone nucleus is also indispensible thiazolidinone derivatives 23 prepared from heterocycle
linked aminobenzenes. The α-bromopropanoic acid
ester derivative prepared from substituted aminoben-
zene leads to α-alkylthiocarboxylic acids 19 and Tyro-
sine derivatives 24 are of immense importance for the
treatment of T2D. Reviewing the synthetic application
of the discussed, our work is projected upon three
∗ For correspondence heterocycles and the two functional groups mentioned.
1063
1064 Raman K Verma et al.

O O
O
NH NH
NH N N S N S
O N
S O O
N O O
O O
Pioglitazone Rosiglitazone BRL 49653 BRL 48482

O O
NH O
NH
N S
O N O
O O O

DRF 2189 Reglitazar JTT 501

O O O
O
O O OH OH
N
N N O O O
O O O O

JTT Compound Ragaglitazar DRF 2725 Novo Nordisk Compound

O
O H O
O
O H
N O HN O
N HN
O
O
O

GW 409544 Farglitazar

Figure 1. PPAR activating molecules.

2. Experimental catalyst was filtered through diatomaceous earth/celite

and the filtrate was evaporated under reduced pressure
2.1 Materials and methods to give a residue which upon trituration with hexane
or upon column chromatography (hexane/EtOAc, 1:5)
All the chemicals used in the present work were pur- gave the desired compound as a solid.
chased from SD Fine Chemical and Aldrich Chemi-
cal Company. The melting/boiling points reported here
were recorded using an open conc. sulphuric acid bath 2.2a 4-[(1-Methyl-1H-benzimidazol-2-yl)methoxy]-
and are uncorrected. The Infrared and 1 H NMR spec- aniline (compound 3, scheme 1): Yield: 75%,
tra of these compounds were recorded on Perkin-Elmer mp: 138–140◦ C; FTIR (KBr): 3447, 3317, 2942,
Spectrum RX FTIR Spectrophotometer and AC400F, 2840, 1512, 1480, 1446, 1364, 1246, 1035, 831,
400 MHz Bruker spectrometer at RSIC, Panjab Uni- 747. cm−1 ; 1 H NMR (CDCl3 ) δ: 7.76 (d, 2H), 7.36–
versity, Chandigarh. LCMS of these compounds were 7.27 (m, 3H), 6.89 (d, J = 6.56 Hz, 1H), 6.63 (d, J =
recorded on LCMS LCQ Finnigan Matt (APCI +ve 6.64 Hz, 2H), 5.30 (s, 2H), 3.88 (s,3H), 2.78 (br.s, 2H);
mode) at Central Instrumentation Lab, NIPER, SAS LCMS m/z (254) [M+1]+ ; Anal. Calcd for C15 H15 N3 O:
Nagar, Mohali, Punjab. GCMS and Elemental analy- C, 71.13; H, 5.97; N, 16.59. Found: C, 71.75; H, 5.68;
sis of these compounds were carried out on Shimadzu N, 16.82.
GCMS-QP2010 Plus and VarioMICRO VI Elemen-
tal Analyzer respectively at Instrumental Laboratory,
2.2b 4-[(1-Methyl-1H-indol-2-yl)methoxy]aniline
Department of Chemistry, Punjabi University, Patiala.
(compound 7, scheme 2): Yield: 50%, mp: 141–
143◦ C; FTIR (KBr): 3500–3200, 2923, 2840, 1656,
2.2 General procedure for the synthesis 1593, 1511, 1468, 1380, 1232, 1010, 832, 751 cm−1 ;
of heterocyclyl linked anilines 3, 7 and 11
1
H NMR (CDCl3 )δ: 7.59 (d, 1H), 7.33–7.31 (m, 1H),
7.25–7.21 (m, 1H), 7.11–7.07 (m, 1H), 6.84 (d, J =
To (3.1 mmol) of the respective nitro compound 8.8Hz, 2H), 6.66–6.63 (d„ J = 8.8Hz, 2H), 6.54 (s, 1H),
(2,6,10) placed in a Parr bottle with 10% Palladium 5.10 (s, 2H), 3.80 (s, 3H); LCMS m/z (253) [M+1]+ ;
on charcoal (300 mg) and methanol/dioxane (150 ml), Anal. Calcd for C16 H16 N2 O: C, 76.16; H, 6.39; N,
and the mixture was hydrogenated at 20 psi for 2 h. The 11.10. Found: C, 76.45; H, 6.07; N, 11.44.
 Heterocyclyl linked anilines and benzaldehydes 1065

O
O N Br
+ d O
N O N N O NH2 e
- N
c O 3a
N N
N OH 2 3
O
N f O
O NH
1a N h N S
N Cl H O
g N O
4 N
N
4a
1b
a i
b
O

O
NH2.HCl N
O O O
N
NHCH3.HCl
4b d
1
O

O
N O
O O
N

4c

Scheme 1. Synthesis of benzimidazolyl linked compounds. a: Glycolic acid, H2 O,

Reflux; b: chloroacetic acid, H2 O, reflux; c: 4-chloronitrobenzene, NaH, DMF, rt; d:
Pd/C-H2 , methanol, rt; e: methanol, acetone,HBr, NaNO2 , methyl acrylate,Cu2 O; f: 4-
fluorobenzaldehyde, NaH, DMF, rt; g: 4-hydroxybenzaldehyde, NaH, DMF, rt; h: 2,4-
thiazolidinedione, piperidinium acetate, toluene, reflux; i: diethyl malonate, piperidinium
acetate, toluene, reflux.

O
+ O NH2
O N d
-
O
c N
OH N
6 7 O

N O NH
e O S
f O
5b H O
N
N
8 8a
b

g
O

N O O

5a O
O O O
a
N

O 8b

N O
H
5

Scheme 2. Synthesis of indolyl linked compounds. a: CH3 I, NaH, DMF; b: LiAlH4 -

THF; c: 4-chloro nitrobenzene, NaH, DMF, rt; d: Pd/C-H2 , methanol; e: 4-fluoro-
benzaldehyde, NaH, DMF, rt; f: 2,4-thiazolidinedione, piperidinium acetate, toluene,
reflux; g: piperidinium acetate, toluene, reflux.

2.2c 10-[3-(4-Aminophenoxy)propyl]acridin-9(10H)- 100) [M+1]+ ; Anal. Calcd for C22 H20 N2 O2 : C, 76.72;
one (compound 11, scheme 3): Yield: 86%, mp: 151– H, 5.85; N, 8.13. Found: C, 76.59; H, 5.57; N, 8.29.
153◦ C; FTIR (KBr): 3335, 3500–3200, 2924, 2840,
1629, 1595, 1509, 1491, 1459,1375, 820, 753 cm−1 ;
1
H NMR (CDCl3 )δ: 8.60–8.57 (m, 2H), 7.71–7.67 2.3 General procedure for the synthesis of
(m, 2H), 7.64–7.62 (d, 2H), 7.31–7.27 (m, 2H), 6.81 heterocyclyl linked benzaldehydes 4 and 8
(d, J = 8.8 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 4.63
(t, J = 7.5 Hz, 2H), 4.08 (t, J = 5.3 Hz, 2H), 3.48 (br.s, To a stirred suspension of sodium hydride (1.4 mmol,
2H), 2.38 (quintet, J = 2.8 Hz, 2H); LCMS m/z (345, 60% w/w dispersion) in dry DMF (20 ml) was added
1066 Raman K Verma et al.

O
+
N -
O
O
+ NH2
HO N -
O c
N O
a N O
O O
+ O 11
N -
O 10
Br O
9a

O N H b

O
O
H
H
Br O
9
9b N O

O
a 12
O

HO

Scheme 3. Synthesis of acridonyl linked compounds. a: 1,3-Dibromopropane, K2 CO3 ,

acetone; b: KOH, DMF (MW); c: Pd/C-H2 , methanol.

(1a/5b) (1.2 mmol) in dry DMF (5 ml) at 0◦ C, and 2H), 7.62 (d, 1H), 7.35–7.33 (m, 1H), 7.28–7.24 (m,
the mixture was stirred for 30 min at room tempera- 1H), 7.13 (d, J = 8.76 Hz, 2H), 6.63 (s, 1H), 5.29
ture (rt) (ca. 30◦ C). A solution of 4-fluorobenzaldehyde (s, 2H), 3.82 (s, 3H); LCMS m/z (266) [M+1]+ ; Anal.
(1.3 mmol) in dry DMF (5 ml) was added drop-wise Calcd for C17 H15 NO2 : C, 76.96; H, 5.70; N, 5.28.
over 15 min at 0◦ C, and stirred for 24 h at rt. The reac- Found: C, 76.58; H, 5.55; N, 5.60.
tion mixture was quenched with water and extracted
with EtOAc (3 × 30 ml). The combined organic extracts
were washed with brine, dried over anhydrous Na2 SO4 , 2.4 Synthesis of 4-[3-(9-oxoacridin-10(9H)-yl)pro-
and concentrated. The residue was chromatographed poxy]benzaldehyde (compound 12, scheme 3)
over silica gel using a mixture of methanol and
dichloromethane (1:10). To a mixture of acridone (9) (0.097 g, 0.5 mmol)
Compound 4 was also prepared by reacting 2- in DMF (15 ml) in a beaker, was added 4-(3-
(chloromethyl)-1-methyl-1H benzimidazole (1b) with bromopropoxy)benzaldehyde (9b) (0.146 g, 0.6 mmol)
4-hydroxybenzaldehyde in the presence of sodium and KOH (0.200 g, 3.6 mmol). The mixture was irra-
hydride taken in DMF following similar procedure. diated in a microwave oven for 5 min at 320 W, and
then the reaction mixture was poured into water (10 ml)
with stirring. After filtration of the insoluble materials,
2.3a 4-[(1-Methyl-1H-benzimidazol-2-yl)methoxy]-
the filtrate was neutralized (pH 7.0) with 2M- HCl, and
benzaldehyde (compound 4, scheme 1): Yield: 30 and
extracted with EtOAc (3 × 25 ml). The organic lay-
58.20%, mp: 120–122◦ C; FTIR (KBr): 2926, 2823,
ers were combined, washed with brine and water, dried
2733, 1697, 1601, 1577,1482, 1430, 1363, 1247,1005,
over Na2 SO4 and evaporated. The pure product (12)
828, 749 cm−1 ; 1 H NMR (CDCl3 )δ: 9.88 (s, 1H),
was obtained as a yellow solid (0.030 g, 16.8%) by co-
7.86–7.81 (m, 3H), 7.42–735 (m, 3H), 7.25–7.23 (d,
lumn chromatography of the residue using methanol–
J = 9.44 Hz, 2H), 5.52 (s, 2H), 3.91 (s, 3H); GCMS
dichloromethane (1:99) mixture as eluent: mp 138–
m/z (%):266, 25) [M]+ , 145 (100); Anal. Calcd for
140◦ C; FTIR (KBr): 2954, 2880, 1685, 1600, 1496,
C16 H14 N2 O2 : C, 72.16; H, 5.30; N, 10.52. Found: C,
1462, 1314, 1258, 1160, 1057, 832, 761 cm−1 ; 1 H NMR
72.51; H, 5.57; N, 10.19.
(CDCl3 )δ: 9.85 (s, 1H), 8.54–8.52 (m, 2H), 7.81 (d,
J = 8.76 Hz, 2H), 7.64–7.62 (m, 2H), 7.60–7.53 (m,
2.3b 4-[(1-Methyl-1H-indol-2-yl)methoxy]benzal- 2H), 7.25–7.21 (m, 2H), 6.98 (d, J = 8.76, 2H), 4.61(t,
dehyde (compound 8, scheme 2): Yield: 30%, mp: J = 7.6 Hz, 2H), 4.15(t, J = 4.8 Hz, 2H), 2.40 (quin-
158–160◦ C; FTIR (KBr): 2933, 2823, 2733, 1697, tet, J = 6.4 Hz, 2H); LCMS m/z (358, 100) [M+1]+ ;
1598, 1506, 1468, 1380, 1244, 1160, 828, 754 cm−1 ; Anal. Calcd for C23 H19 NO3 : C, 77.29; H, 5.36; N, 3.92.
1
H NMR (CDCl3 ) δ: 9.90 (s, 1H), 7.86 (d, J = 8.76 Hz Found: C, 77.61; H, 5.57; N, 28.19.
 Heterocyclyl linked anilines and benzaldehydes 1067

2.5 Synthesis of methyl 2-bromo-3-{4-[(1-methyl-1H- 7.47–7.41 (m, 3H), 7.36–7.29 (m, 2H), 7.21–7.19;7.20
benzimidazol-2-yl)methoxy]phenyl} propanoate (d, J = 8.80 Hz, 2H), 5.46 (s, 2H), 3.91 (s, 3H); LCMS
(compound 3a, scheme 1) m/z (366) [M+1]+ ; Anal. Calcd for C19 H15 N3 O3 S: C,
62.45; H, 4.14; N, 11.50; S, 8.78. Found: C, 62.79; H,
To a slurry of (3) (1 g, 3.9 mmol) in methanol (10 ml) 4.135; N, 11.34; S.8.951.
and acetone (10 ml), cooled to −10◦ C, was added 48%
aqueous HBr (0.83 ml, 15 mmol). The mixture was
stirred at 0◦ C for 5 min, and a solution of sodium 2.6b Synthesis of 5-{4-[(1-methyl-1H-indol-2-yl)-
nitrite (0.290 g, 4.2 mmol) in water (1 ml) was added methoxy]benzylidene}-1,3-thiazolidine-2,4-dione (8a,
drop-wise so as to keep the reaction temperature below scheme 2): Yield: 32.0%, mp: 173–175◦ C; FTIR
5◦ C. The mixture was stirred at 0–5◦ C for 15 min, (KBr): 3402, 2926, 2850, 2588, 1732, 1701, 1595,
and then methyl acrylate (2 ml, 23 mmol) was added 1508, 1482, 1334, 1289, 1250, 1157, 1013, 820,
drop-wise. The mixture was warmed to 38◦ C, pow- 735 cm−1 ; 1 H NMR (DMSO-d6 )δ: 7.61 (d, 1H), 7.48
dered cuprous oxide (120 mg, 0.84 mmol) was added, (d, J = 8.60 Hz, 2H), 7.35 (d, 1H), 7.22 (m, 1H), 7.11
and the mixture was stirred for 2 h at the same tem- (d, J = 8.60 Hz, 3H), 7.07 (d, 1H), 6.61 (s, 1H), 5.28
perature, then made basic with concentrated aqueous (s, 2H), 3.81 (s, 3H); LCMS m/z (365) [M+1]+ ; Anal.
ammonia, and extracted with EtOAc (3 × 20 ml). The Calcd for C20 H16 N2 O3 S: C, 65.92; H, 4.43; N, 7.69; S,
combined extracts were washed with water and brine, 8.80. Found: C, 65.72; H, 4.78; N, 7.75; S, 8.63.
dried over anhydrous Na2 SO4 , and concentrated. The
title compound (3a) was isolated by column chro- 2.7 General procedure for the synthesis
matography MeOH/DCM (1:10) as a pale brown solid of heterocyclyl linked diethyl benzylidene
(0.235 g, 15%): mp 83–85◦ C; FTIR (KBr): 2926, 2855, propanedioates 4b and 8b
1734, 1600, 1486, 1406, 1364, 1239, 1016, 817, 750,
503 cm−1 ; 1 H NMR (CDCl3 )δ: 7.80–7.78 (m, 2H), A solution of (4/8) (2.8 mmol) and diethyl malonate
7.40–7.27 (m, 3H), 7.15–7.13 (d, J = 8.68 Hz, 2H), (5.1 mmol) in toluene (30 ml) containing a catalytic
7.04–7.01 (d, J = 8.68 Hz, 2H), 5.37 (s, 2H), 4.34 (dd, quantity of piperidinium acetate was refluxed for 7 h.
J = 6.96 Hz, 1H), 3.89 (s, 3H), 3.72 (s, 3H), 3.40(dd, After cooling to rt, the solution was concentrated.
J = 6.9 Hz, 1H), 3.18 (dd, J = 6.9 Hz, 1H); GCMS The residue was chromatographed using a mixture of
m/z (%): 402(3.8) [M]+ , 404(4) [M+2]+ and 145 (100); MeOH and DCM (1:99) or EtOAc and hexane (1:10) to
Anal. Calcd for C19 H19 BrN2 O3 : C, 56.69; H, 4.75; N, give (4b/8b) as white solid.
6.95. Found: C, 56.85; H, 4.57; N, 6.73.

2.7a Diethyl {4-[(1-methyl-1H-benzimidazol-2-yl)-

2.6 General procedure for the synthesis methoxy]benzylidene} propanedioate (4b, scheme 1):
of heterocyclyl linked benzylidene-1,3- Yield: 45%, mp: 128–130◦ C; FTIR (KBr): 2978, 2934,
thiazolidine-2,4-diones 4a and 8a 2850, 1723, 1600, 1514,1471, 1399, 1260, 1212, 1175,
1064, 1013, 839, 744 cm−1 ; 1 H NMR (CDCl3 )δ: 7.79–
A mixture of (4/8) (0.25 mmol), thiazolidine-2,4- 7.77 (m, 1H), 7.64 (s, 1H), 7.42–7.40 (d, J = 8.80 Hz,
dione (0.25 mmol) and catalytic quantity of piperi- 2H), 7.37–7.27 (m, 3H), 5.42 (s, 2H), 7.09 (d, J =
dinium acetate in toluene (50 ml) was refluxed for 8.8, 2H), 4.30 (two overlapping quartet, J = 7.2 Hz,
7 h with continuous removal of water using a Dean– 4H), 3.88 (s, 3H), 1.31 (t, J = 7.1Hz, 3H), 1.29 (t, J =
Stark water separator. The reaction mixture was 7.7 Hz, 3H); LCMS m/z (409) [M+1]+ ; Anal. Calcd
cooled to rt and then stored inside a refrigerator for C23 H24 N2 O5 : C, 67.63; H, 5.92; N, 6.86. Found: C,
overnight. The yellow precipitate was collected by 67.82; H, 6.21; N, 6.61.
filtration under suction, washed with hexane, and dried
to obtain (4a/8a) as pale yellow solid.
2.7b Diethyl {4-[(1-methyl-1H-indol-2-yl)methoxy]-
benzylidene} propanedioate (8b, scheme 2): Yield:
2.6a 5-{4-[(1-Methyl-1H-benzimidazol-2-yl)methoxy]- 20.00%, mp: 108–110◦ C; FTIR (KBr): 2979, 2920,
benzylidene}-1,3-thiazolidine-2,4-dione (4a, scheme 1): 2850, 1720, 1602, 1511, 1464, 1381, 1340, 1263, 1207,
Yield: 40%, mp 271–273◦ C; FTIR (KBr): 3410, 2948, 1178, 1007, 833, 751 cm−1 ; 1 H NMR (CDCl3 )δ: 7.67
2850, 2532, 1730, 1704, 1580, 1509, 1482, 1450, 1408, (s, 1H), 7.61 (d,1H), 7.44 (d, J = 8.8 Hz, 2H), 7.34 (d,
1334,1286, 1253, 1176, 1009, 831, 740 cm−1 ; 1 H NMR 1H), 7.25 (m, 1H), 7.12 (m, 1H), 7.01 (d, J = 8.8 Hz,
(DMSO-d6 )δ: 7.75–7.73; 7.74 (d, 1H), 7.68 (s, 1H), 2H), 6.61 (s, 1H), 5.22 (s,2H), 4.35 (q, J = 7.1 Hz,
1068 Raman K Verma et al.

2H), 4.29 (q, J = 7.1 Hz, 2H), 3.79 (s, 3H), 1.33 (t, amine (7) was similarly obtained by reduction of (6).
J = 4.3 Hz, 3H), 1.31 (t, J = 4.4 Hz, 3H); LCMS m/z The benzylidenes (8b) and (8a) were obtained from
(407) [M+1]+ ; Anal. Calcd for C24 H25 NO5 : C, 70.46; (8) by condensation with diethyl malonate and 2,4-
H, 6.18; N, 3.44. Found: C, 70.13; H, 5.89; N, 3.27. thiazolidinediones, respectively.
Acridonyl linked aldehyde and nitro compounds
were synthesized according to scheme 3. Acridone 26
2.8 Synthesis of diethyl{4-[(1-methyl-1H- (9) brormopropoxybenzaldehyde 20 (9b), and brormo-
benzimidazol-2-yl)methoxy]benzyl} propanedioate propoxynitrobenzene 20 (9a) were prepared by known
(compound 4c, scheme 1) procedures. The aldehydes (12) and the nitro compound
(10) were prepared by microwave irradiation of (9)
A solution of 4b (400 mg, 0.98 mmol) in a mixture of
and the corresponding bromo propoxy compounds 27
methanol and dioxane (125:50) was shaken in the pres-
(9b and 9a), (10a) was subsequently reduced to obtain
ence of 10% Pd-C (100 mg) in a Parr Hydrogenator
corresponding amine (11).
under 20 psi H2 pressure at rt for 12 h. The mixture was
filtered through celite, and the filtrate was evaporated
under reduced pressure. The residue upon recrystalliza- 4. Conclusion
tion from methanol gave 4c (100 mg, 25%) as an off
white solid: mp 135–136◦ C; FTIR (KBr): 2978, 2935, We report here the syntheses of benzaldehydes and
2850, 1733,1610, 1511, 1475, 1372, 1235, 1147, 1037, anilines linked at the para position, with an alkoxy
1013, 825, 744 cm−1 ; 1 H NMR (CDCl3 )δ: 7.78–7.76 ether linkage to three crucial heterocycles namely,
(m, 1H), 7.36–7.27 (m, 3H), 6.99–6.97 (m, 2H), 5.35 benzimidazole, indole and acridone. Representative
(s, 2H), 4.14 (two superimposed quartet, J = 2.7 Hz, procedure for the preparation of 1,3-diester, 2,4-
4H), 3.87 (s, 3H), 3.57 (t, J = 7.8 Hz, 1H), 3.14 (d, thiazolidinedione and α-bromopropanoic acid ester
J = 7.8 Hz, 2H), 1.18 (two superimposed triplet, J = derivatives in case of benzimidazole, and 1,3-diester
14.3 Hz, 6H); LCMS m/z (411) [M+1]+ ; Anal. Calcd and 2,4-thiazolidinedione derivative in case of indole-
for C23 H26 N2 O5 : C, 67.30; H, 6.38; N, 6.82. Found: C, based precursors has been optimized, and the said
67.47; H, 6.26; N, 6.59. compounds have been successfully synthesised and
characterised.

3. Results and discussion Acknowledgements

The benzimidazolyl linked aldehyde and amino com- Authors acknowledge the financial support from
pounds were prepared by the synthetic route as shown IndSwift Labs. Ltd. (ISLL), SAS Nagar, Mohali for the
in (scheme 1). N -methyl-1,2-phenylene diamine dihy- ISLL-Punjabi University Collaborative Research, and
drochloride (1) was cyclised drastically with glycolic providing the research fellowship to two of the authors
acid and chloroacetic acid to furnish the correspond- VK and PG.
ing hydroxyl-(1a) and chloro-(1b) compounds, respec-
tively in excellent yields. These were reacted with
4-fluorobenzaldehyde 25 and 4-hydroxobenzaldehyde to References
afford the aldehyde (4). The latter was condensed with
1. (a) Porcari A R, Devivar R V, Kucera L S, Drach J C and
diethyl malonate 18 and 2,4-thiazolidinedione 16 to give Townsend L B 1998 J. Med. Chem. 41 1252 (b) Migawa
the benzylidenes (4b) and (4a), respectively. Catalytic M T, Girardet J, Walker II J A, Koszalka G W, Cham-
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