Novel synthesis of 1,2,4-triazolophanes and 1,3,4-oxadiazolophanes: A dieckmann condensation approach

Article abstract of DOI:10.1002/jhet.729

The Dieckmann condensation has been used for the first time for the syntheses of novel 1,2,4-triazolophanes and 1,3,4-oxadiazolophanes. The bis-1,3,4-oxadiazol-2-thiols 1a and 1b were reacted with ethyl bromoacetate to give the diesters 2a and 2b. Diester

Full text of DOI:10.1002/jhet.729

March 2012
Novel Synthesis of 1,2,4-Triazolophanes and
1,3,4-Oxadiazolophanes: A Dieckmann Condensation Approach
329
Madhukar S. Chande, C. Sajithkumar, Hemant S. Mondkar,*
Pravin A. Barve, and Sachin Diwan
Department of Chemistry, The Institute of Science, 15 Madam Cama Road, Mumbai 400032, India
*E-mail: hemantmondkar@gmail.com
Received June 9, 2010
DOI 10.1002/jhet.729
Published online 19 December 2011 in Wiley Online Library (wileyonlinelibrary.com).
The Dieckmann condensation has been used for the first time for the syntheses of novel 1,2,4-triazo-
lophanes and 1,3,4-oxadiazolophanes. The bis-1,3,4-oxadiazol-2-thiols 1a and 1b were reacted with
ethyl bromoacetate to give the diesters 2a and 2b. Diesters 2a and 2b were treated under dry conditions
with sodium methoxide in methanol to afford desired symmetrical 1,3,4-oxadiazolophanes 3a and 3b.
Similarly, diesters of macrocycle precursors containing 1,2,4-triazole moiety, that is, 6a, 6b, 10, 13a,
13b, and 13c were synthesized from 5a, 5b, 9, 12a, 12b, and 12c, respectively. Dieckmann condensa-
tion of these diesters afforded symmetrical ketones 7a, 7b, 11, 14a, 14b, and 14c. Extrusion of CO2
was observed after in situ hydrolysis of the conventional Dieckmann product during neutralization by
dilute mineral acids to afford highly symmetrical ketone in good yields. Further, the ketones 14a, 14b,
and 14c were converted into their respective thiones by the reaction with Lawesson’s reagent. All the
products were synthesized with good yields, and structures were confirmed by various spectroscopic
tools and elemental analyses.
J. Heterocyclic Chem., 49, 329 (2012).
INTRODUCTION
reports focus on the synthesis of pulvinones [25], indolizi-
dines [26], mycophenloic acid [27], and rutaecarpine [28].
We now report for the first time the synthetic applica-
tions of Dieckmann condensation for the construction of
macrocyclic ethers.
A progressive interest has been directed in the last
few years to the chemistry of crown ethers containing
heterocyclic rings on the periphery of the macrocyclic
system. These macrocycles were found to exhibit inter-
esting host–guest complexation characteristics [1,2] and
biochemical properties [3]. Incorporation of heterocyclic
moieties within the cavity of the macrocyclic rings not
only provides rigidity but also helps to participate in
complexation through their soft donor atoms. Macrocy-
clic ethers with pyridine and other nitrogen containing
heterocyclic subunits were reported to form strong and
selective interactions with various charged and neutral
guest molecules [4–7]. In a recent communication, we
have reported the synthesis of various novel aminotria-
zolophanes [8] and thiatriazolophanes with various
1,2,4-triazole macrocyclic precursors [9].
The reaction is most successful for the synthesis of five-,
six-, and seven-membered rings, whereas it either failed or
resulted in very poor yields for 9- to 12-membered rings
[29]. In case of forming 13-membered or larger ring sys-
tems by Dieckmann condensation, because of the probabil-
ity of intermolecular reactions when the esters are reacted
under usual dilutions, the ring closure is generally carried
out according to high dilution techniques [30].
In accordance with these findings, we could obtain the
product in usual dilution condition in all cases. In contin-
uation [31–35] of our research interest in synthesizing
novel macrocyclic crown ethers containing heterocyclic
subunits, we now report here the synthesis of 1,2,4-triazo-
lophanes and 1,3,4-oxadiazolophanes using Dieckmann
condensation. To our knowledge, this is the first report
on the macrocyclic ring closure using Dieckmann con-
densation for the synthesis of 1,2,4-triazolophanes and
1,3,4-oxadiazolophanes.
Intramolecular diester cyclization to give cyclic b-Keto
esters is commonly known as the Dieckmann condensation
[10]. An enormous number of examples for the construc-
tion of carbon systems with varying ring size using this
reaction have been reported [11–24]. Some of the recent
C
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M. S. Chande, C. Sajithkumar, H. S. Mondkar, P. A. Barve, and S. Diwan
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Scheme 1. Synthesis of 1,3,4-oxadiazolophanes.
Further, the carbonyl groups of these macrocycles so
synthesized were converted into thione by treating with
Lawesson’s reagent as per the reported methods [36].
The steps from ester to carbalkoxyketone involve the
use of a strong base, a base, which acts practically irre-
versibly for best results, but since the hydrolysis and
decarboxylation steps may not require strong acid treat-
ment; the latter feature directed the hydrolysis followed
by decarboxylation to afford the symmetrical ketone
instead of conventional b-ketoesters [11].
The N,N-disubstituted 1,2,4-triazole macrocycle pre-
cursors 5a and 5b [9] were similarly treated with potas-
sium hydroxide and ethylbromoroacetate to afford the
diesters 6a and 6b. Subsequent exposure of the diesters,
6a and 6b, to Dieckmann condensation conditions
afforded the triazolophanes 7a and 7b (Scheme 2) with
60–63% yield.
RESULTS AND DISCUSSION
In the present investigation, we have carried out the
Dieckmann cyclization of the diesters (e.g., 2a) using
sodium methoxide as a base in dry methanol, under
moderate to high dilution conditions with high speed
stirring in nitrogen atmosphere. The 1,2,4-oxadiazole [34]
macrocycle precursors, for example, 1a and 1b were
treated with potassium hydroxide in methanol. The salt
generated in situ was treated with ethylbromoacetate to
afford the diesters, for example, 2a and 2b. Diesters 2a
and 2b were then subjected to Dieckmann condensation
using metal alkoxides, that is, sodium methoxide in meth-
anol at room temperature under nitrogen atmosphere. The
shift in the carbonyl peak in the IR spectrum of the com-
pounds 3a and 3b suggested the conversion of the diester
into cyclic ketone (Scheme 1). The 1H and 13C NMR
spectra, HRMS, and elemental analyses of the compounds
are in agreement with the proposed structures.
In another approach, 4-phenyl-5-(20-hydroxy-
phenyl)-3-mercapto-1,2,4-triazole (8) was synthesized
as per the known procedure [37]. Reaction of 8 with
1,3-dibromo-propane (2:1 mol ratio) in methanol
afforded 1,3-bis[4-phenyl-5(20-hydroxyphenyl)-1,2,4-
Monoketones (3a, 3b) and diketone (4; Fig. 1) were
collected and identified. However, increasing the dilu-
tion avoided formation of dimmer/diketone. As it was
not a part of our research interest, no attempt was made
to isolate and characterize any diketones, triketones, or
polymeric products except (4), its structure was later
1
confirmed by H NMR, 13C NMR, HRMS, and elemen-
tal analyses.
Figure 1. Diketone 4.
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Novel Synthesis of 1,2,4-Triazolophanes and 1,3,4-Oxadiazolophanes: A Dieckmann
Condensation Approach
331
Scheme 2. Synthesis of triazolophanes through Dieckmann condensation.
triazol-3-yl]mercaptopropane (9). Further, diester 10 was
obtained by reaction of compound 9 with ethylbromoace-
tate. Dieckmann cyclization of diester 10 afforded sym-
metrical ketone 11 in 46% yields (Scheme 3).
compounds; and the structures were confirmed through
mix melting point and CO-IR.
In conclusion, we were successful in using the Dieckmann
condensation reaction for the synthesis of macrocyclic aza
crown ethers containing 1,2,4-triazole and 1,3,4-oxadiazole
units. This report also highlights the synthesis of hetero-
phanes containing 10 or more members in good yields.
The scope of the Dieckmann condensation was further
explored with compounds, 12a, 12b, and 12c [9], which
on reaction with ethylbromoacetate afforded respective
diesters 13a, 13b, and 13c. Dieckmann condensation of
these diesters resulted symmetrical ketones 14a, 14b, and
14c in good yields (Scheme 4), further these ketones
were reacted with Lawesson’s reagent in refluxing tolu-
ene to achieve thionation of the ketone macrocycles
(Scheme 5). The absence of the characteristic carbonyl
peak in the IR and carbonyl carbon in 13C NMR, finally
mass spectrum confirmed the structures of the com-
pound 14a, 14b, and 14c. We were also successful in
using microwave irradiation technique to facilitate the
thionation reaction in some cases of the synthesized
EXPERIMENTAL
General experimental procedures. All chemicals were
obtained from E-Merck and Qualigens. Solvents were purified
according to reported methods. The progress of the reactions
was followed with TLC using silica gel SILG/UV 254 plates.
Chromatography was carried on a column over silica gel 60,
0.063–0.200mm (70–230 mesh ASTM). IR spectra were run
on a Perkin Elmer 257-FTIR 1600 spectrophotometer using
potassium bromide (KBr) discs. The 1H and 13C NMR (300
MHz) were run on a Jeol AL-300 spectrometer (d in ppm, J in
Scheme 3. Synthesis of lariat triazolophanes ethers via Dieckmann condensation.
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M. S. Chande, C. Sajithkumar, H. S. Mondkar, P. A. Barve, and S. Diwan
Vol 49
Scheme 4. Conversion of the crown precursor to macrocycle through Dieckmann condensation.
Hz). Mass spectra were recorded on a Shimadzu GCMS-QP
2010. The C, H, N, S analysis of the compounds were carried
out at UICT, Analytical Chemistry Department, Mumbai and
are in agreement with the theoretical values. Melting points
were taken in open capillaries and are uncorrected.
were at m/z 387, 358, 300, 341, and 94. Anal. (calcd./found in
%) for C15H20N4O6S2: C, 43.2/43.5; H, 4.84/4.63; N, 13.45/
13.53; S, 15.40/15.60.
A similar protocol was used for the syntheses of other die-
sters namely 2b, 6a, 6b, 10, 13a, 13b, and 13c.
Synthesis of 1,3-bis[(5-carbethoxymethylmercapto)-1,3,4-
oxadiazol-2-yl]propane (2a). 1,3-Bis(5-mercapto-1,3,4-oxadia-
zol-2-yl)propane (2.58 g, 10 mmol) and KOH (1.12 g, 20
mmol) in 20 mL of methanol were mixed together at 0ꢀC. To
the slurry thus obtained, ethyl bromoacetate (3.34 g, 20 mmol)
was added portion wise over a period of 20–30 min at 0ꢀC.
The reaction workup was carried out by addition of water and
subsequent extraction with dichloromethane. The organic layer
was washed with 2% NaOH solution, aqueous NH4Cl, distilled
water, and finally was dried over sodium sulphate and concen-
trated. The product thus obtained was sufficiently pure to be
used without further purification. m.p. 90–92ꢀC, Yield: 86%.
IR (KBr, cmꢁ1): 2964.3, 2920.1, 1752.6, 1584.4, 1495.3,
Synthesis of 2,6-dithia-1,7(2,5)-1,3,4-oxadiazola-cyclodeca-
phane-4-one (3a). The diester of 1,4-bis[(5-carbethoxymethyl-
mercapto)-1,3,4-oxadiazol-2-yl]butane (4.58 g, 10 mmol) was
stirred with sodium methoxide (0.54 g, 10 mmol) in dry meth-
anol (100 mL) under anhydrous conditions for 6 h. The reac-
tion mixture was then poured onto crushed ice and acidified
with dil. hydrochloric acid. The colorless solid was filtered,
washed with water, and dried. Compound was further purified
by column chromatography using ethyl acetate:hþexane (8:2).
m.p. 163–165ꢀC. Yield: 55%. HRMS: Found M 298.3408;
C10H10N4O3S2 requires 298.3414. IR (KBr, cmꢁ1): 2934.9,
1721.9, 1585.3, 1491.4, 1262.7, and 1170.8. 1H NMR
(CDCl3): d 1.87 (quintet, 2H, J ¼ 7.0 Hz, H1), 2.93 (t, 4H,
J ¼ 7.0 Hz, H2), 4.09 (s, 4H, H5). 13C NMR (CDCl3): 25.59
(C1), 34.67 (C2), 53.56 (C5), 161.30 (C3), 165.72 (C4), and
170.60 ppm (C6). MS (DI): Mþ at m/z 398. The other main
fragmentation peaks were at m/z 242, 126 and 94. Anal.
(calcd./found in %) for C10H10N4O3S2: C, 40.3/40.5; H, 3.38/
3.52; N, 18.78/18.58; S, 21.49/21.58.
1
1302.2, 1153.8, and 1025.4. H NMR (CDCl3) : d 1.31 (t, 6H,
J ¼ 6.5 Hz, 2x AOCH2CH3), 1.98 (quintet, 2H, J ¼ 6.5 Hz,
H1), 2.98 (t, 4H, J ¼ 6.5 Hz, H2), 4.16 (s, 4H, H5) and 4.29
(q, 4H, J ¼ 6.5 Hz, AOCH2). 13C NMR (CDCl3): 14.06 (2x
AOCH2CH3), 20.54 (C1), 22.16 (C2), 32.04 (C5), 62.11 (2x
AOACH2), 154.78 (C3), 164.19 (C4), and 168.12 ppm (C6).
MS (DI): Mþ at m/z 416. The other main fragmentation peaks
Scheme 5. Thionation by Lawesson’s reagent.
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Novel Synthesis of 1,2,4-Triazolophanes and 1,3,4-Oxadiazolophanes: A Dieckmann
Condensation Approach
333
Similar protocol was used for the synthesis of 3b, 7a, 7b,
11, 14a, 14b, and 14c.
Synthesis of 4-bis[4-phenyl-5-(carbethoxy methylmercapto)-
1,2,4-triazol-3-yl] butane (6b). m.p. 137–139ꢀC, Yield: 75%.
IR (KBr, cmꢁ1): 3136.3, 2957.2, 1769.8, 1620.4, 1502.3,
1334.1, and 1228.4. H NMR (CDCl3) : d 1.16 (t, 6H, J ¼ 7
Synthesis of 1,4-bis[(5-carbethoxymethylmercapto)-1,3,4-
oxadiazol-2-yl] butane (2b). m.p. 156–127ꢀC, Yield 83%. IR
(KBr, cmꢁ1): 2987.2, 2919.5, 1765.4, 1584.2, 1495.9, 1302.4,
1
Hz, AOCH2CH3), 2.14 (quintet, 4H, J ¼ 7 Hz, H1), 2.93 (t,
4H, J ¼ 7 Hz, H2), 4.15 (s, 4H, H5), 4.31 (quartet, 4H, J ¼ 7
Hz, 2x AOCH2) and 6.79, 7.23, and 7.52 (m, 10H, Aromatic
H). 13C NMR (CDCl3): 15.12 (2 x AOCH2CH3), 29.12 (C1),
32.32 (C2), 37.13 (C5), 63.12 (2x AOCH2), 129.11, 132.43,
134.22, and 136.23 (4, Aromatic C), 147.24 (C3), 154.35 (C4),
and 170.01 (C6) ppm. MS (DI): Mþ at m/z 580. The other
main fragmentation peaks were at m/z 406, 272, 138, and 110.
Anal. (calcd./found in %) for C28H32N6O4S2: C, 57.91/57.8; H,
5.55/5.37; N, 14.47/14.58; S, 11.0/11.21.
1
1153.1, and 1025.8. H NMR (CDCl3) : d 1.29 (t, 6H, J ¼ 6.0
Hz, 2x AOCH2CH3), 1.89 (quintet, 4H, J ¼ 6.0 Hz, H1), 2.87
(t, 4H, J ¼ 6.0 Hz, H2) and 4.19 (s, 4H, H5) and 4.23 (q, 4H,
J ¼ 6.0 Hz, 2x AOACH2). 13C NMR (CDCl3): 8.82 (2x
AOCH2CH3), 19.65 (C1), 20.16 (C2), 29.14 (C5), 57.13 (2x
AOCH2), 157.69 (C3), 162.19 (C4), and 162.32 (C6) ppm. MS
(DI): Mþ at m/z 430. The other main fragmentation peaks
were at m/z 385, 341, 356, 140, and 108. Anal. (calcd./found
in %) for C16H22N4O6S2: C, 44.64/44.5; H, 5.15/5.26; N, 13.0/
13.11; S, 14.90/14.77.
Synthesis of 14,64-di-t-butyl-2,6-dithia-1,7(3,5)-1,2,4-tria-
zola-cycloundecaphane-4-one (7a). m.p. 153–155ꢀC, Yield
60%. HRMS: Found Mþ 422.6108; C19H30N6OS2 requires
422.6111. IR (KBr, cmꢁ1): 2933.6, 2836.2, 1727.4, 1502.2,
Synthesis of 2,6-dithia-1,7(2,5)-1,3,4-oxadiazola-cyclo unde-
caphane-4-one (3b). m.p. 180–182ꢀC, Yield 63%. HRMS:
Found Mþ 312.3674; C11H12N4O3S2 requires 312.3680. IR
(KBr, cmꢁ1): 2934.9, 1728.9, 1585.3, 1491.4, 1262.7, and
1
1378.0, 1194.2, and 1293.5. H NMR (CDCl3): d 1.75 (s, 18H,
1
2x AC(CH3)3), 1.90 (quintet, 4H, J ¼ 7 Hz, H1), 2.98 (t, 4H,
J ¼ 7 Hz, H2) and 4.15 (s, 4H, H5). 13C NMR (CDCl3): 28.41
(C1), 29.79 (C2), 35.67 (2x AC(CH3)3), 55.45 (C5), 59.0 (2 x
AC(CH3)3), 157.50 (C3), 163.01 (C4), and 170.40 (C6) ppm.
MS (DI): Mþ at m/z 422. The other main fragmentation peaks
were at m/z 308, 252, 136, and 110. Anal. (calcd./found in %)
for C19H30N6OS2: C, 54.0/54.11; H, 17.16/17.29; N, 19.89/
19.68; S, 5.17/5.31.
1170.8. H NMR (CD3OD): d 1.87 (quintet, 4H, J ¼ 6.0 Hz,
H1), 2.93 (t, 4H, J ¼ 6.0 Hz, H2), 4.18 (s, 4H, H5). 13C NMR
(CD3OD): 25.59 (C1), 34.67 (C2), 53.56 (C5), 165.35 (C3),
169.72 (C4), and 170.64 (C6) ppm. MS (DI): Mþ at m/z 312.
The other main fragmentation peaks were at m/z 256, 140, and
108. Anal. (calcd./found in %) for C11H12N4O3S2: C, 42.3/
42.5; H, 3.87/3.62; N, 17.94/17.78; S, 20.53/20.29.
Synthesis of 2,6,13,17-tetrathia-1,7,12,15(2,5)-1,3,4-oxadia-
zola-cyclodocosane-4,15-dione (4). m.p. <300ꢀC, Yield 13%.
HRMS: Found Mþ 624.7352; C22H24N8O6S4 requires
624.7360. IR (KBr, cmꢁ1): 2961.5, 1734.2, 1603.1, 1516.3,
Synthesis of 14,64-di-phenyl-2,6-dithia-1,7(3,5)-1,2,4-tria-
zola-cycloundecaphane-4-one (7b). m.p. 187–189ꢀC, Yield
64%. HRMS: Found Mþ 462.5906; C23H22N6OS2 requires
462.5904. IR (KBr, cmꢁ1): 3134.5, 2973.6, 1732.4, 1510.2,
1
1285.8, and 1182.6. H NMR (DMSO-d6): d 1.66 (quintet, 8H,
1
1378.0, 1194.2, and 1293.5. H NMR (CDCl3): d 2.11 (quintet,
J ¼ 6.0 Hz, H1), 2.68 (t, 8H, J ¼ 6.0 Hz, H2), 4.12 (s, 8H,
H5). 13C NMR (DMSO-d6): 29.62 (C1), 34.63 (C2), 56.18
(C5), 166.12 (C3), 169.96 (C4), and 180.23 (C6) ppm. Anal.
(calcd./found in %) for C22H24N8O6S4: C, 42.3/42.6; H, 3.87/
3.59; N, 17.94/17.83; S, 20.53/20.33.
4H, J ¼ 7 Hz, H1), 2.92 (t, 4H, J ¼ 7 Hz, H2), 4.21 (s, 4H,
H5) and 6.87, 7.12, and 7.46 (m, 10H, Aromatic H). 13C NMR
(CDCl3): 28.41 (C1), 29.79 (C2), 53.95 (C5), 129.16, 131.58,
133.29, and 136. 23 (4, Aromatic C), 154.63 (C3), 163.01
(C4), and 171.32 (C6) ppm. MS (DI): Mþ at m/z 462. The
other main fragmentation peaks were at m/z 406, 138, and
110. Anal. (calcd./found in %) for C23H22N6OS2: C, 59.72/
59.5; H, 4.79/4.59; N, 18.17/18.33; S, 13.86/13.55.
Synthesis of 1,3-bis[4-phenyl-5(20-hydroxyphenyl)-1,2,4-tri-
azol-3-yl]mercaptopropane (9). m.p. 166–168ꢀC, Yield: 75%.
IR (KBr, cmꢁ1): 3068.6, 2946.0, 1621.3, 1565.3, 1502.4,
1334.3, and 1228.5. 1H NMR (CDCl3) : d 2.34 (quintet, 2H,
J ¼ 6.5 Hz, H1), 3.78 (t, 4H, J ¼ 6.5 Hz, H2), 6.58–7.53(m,
18H, Aromatic H) and 11.12 (s, 2H, 2x AOH, D2O-exchange-
able). 13C NMR (CDCl3): 30.32 (C1), 34.16 (C2), 112.28,
113.23, 114.83, 116.43, 117.93, 119.45, 122.41, 126.34, 34.43,
and 155.23(10, Aromatic C), 151.62(C3), 153.53 (C4) ppm.
MS (DI): Mþ at m/z 578. The other main fragmentation peaks
were at m/z 311, 269, 134, and 91. Anal. (calcd./found in %)
for C31H26N6O2S2: C, 64.34/64.5; H, 4.53/4.32; N, 14.52/
14.70; S, 11.08/11.32.
Synthesis of 1,4-bis(5-mercapto-4-t-butyl-1,2,4-triazol-3-yl)bu-
tane (5a). m.p. 213–215ꢀC, Yield 70%. IR (KBr, cmꢁ1):
1
2920.9, 1520.9, 1491.4, 1262.7, and 1170.8. H NMR (DMSO-
d6): d 1.77 (quintet, 4H, J ¼ 6.75 Hz, H1), 1.84 (s, 18H, 2x
AC(CH3)3), 2.92 (t, 4H, J ¼ 6.75 Hz, H2) and 13.13 (s, 2H,
SH). 13C NMR (DMSO-d6): 26.72 (C1), 28.98 (2x AC(CH3)3),
29.85 (C2), 61.72 (2x NAC(CH3)3), 152.85 (C3), and 152.46
(C4) ppm. MS (DI): Mþ at m/z 368. The other main fragmen-
tation peaks were at m/z 312, 256, 115, 142, and 128. Anal.
(calcd./found in %) for C16H28N6S2: C, 52.14/52.28; H, 7.66/
7.52; N, 22.18/22.28; S, 17.40/17.51.
Synthesis of 4-bis [4-t-butyl-5-(carbethoxy methylmer-
capto)-1,2,4-triazol-3-yl] butane (6a). m.p. 178–180ꢀC, Yield
71%. IR (KBr, cmꢁ1): 2947.3, 1770.5, 1557.2, 1502.7, 1307.5,
1
1173.9, 1218.4, and 1029.4. H NMR (CDCl3) : d 1.27 (t, 6H,
J ¼ 6.5 Hz, 2x AOCH2CH3), 1.73 (s, 18H, 2x AC(CH3)3),
2.09 (quintet, 4H, J ¼ 6.5Hz, H1), 2.93 (t, 4H, J ¼ 6.5 Hz,
H2), 4.12 (s, 4H, H5) and 4.18 (quartet, 4H, J ¼ 6.5 Hz, 2x
AOCH2). 13C NMR (CDCl3): 14.02 (2x AOCH2CH3), 27.59
(C1), 29.75 (2x AC(CH3)3), 30.62 (C2), 36.04 (C5), 58.84 (2x
NAC(CH3)3), 61.72 (2x AOCH2), 149.36 (C3), 155.85 (C4),
and 168.61 (C6) ppm. MS (DI): Mþ at m/z 540. The other
main fragmentation peaks were at m/z 426, 282, 190, 136, and
110. Anal. (calcd./found in %) for C24H40N6O4S2: C, 53.31/
53.20; H, 7.46/7.68; N, 15.54/15.88; S, 11.86/11.58.
Synthesis of 1,3-bis[{5-(4-phenyl-20-carbethoxy phenyl)-1,2,4-
triazol-3-yl }mercapto]propane (10). m.p. 144–146ꢀC, Yield:
82%. IR (KBr, cmꢁ1): 3109.6, 2937.8, 1766.9, 1609.7, 1366.4,
1
and 1241.8. H NMR (CDCl3) : d 1.21 (t, 6H, J ¼ 6.5 Hz, 2x
AOCH2CH3), 2.26 (quintet, 2H, J ¼ 6.5 Hz, H1), 3.41 (t, 4H,
J ¼ 6.5 Hz, H2), 4.16 (quartet, 4H, J ¼ 6.5 Hz, 2x AOCH2),
4.14(s, 4H, H5) and 6.58–7.53(m, 18H, Aromatic H). 13C
NMR (CDCl3): 14.12 (2x AOCH2CH3), 29.12 (C1), 32.17
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M. S. Chande, C. Sajithkumar, H. S. Mondkar, P. A. Barve, and S. Diwan
Vol 49
(C2), 61.42 (2x AOCH2CH3), 65.59(C5), 112.28, 116.42,
118.39, 120.42, 122.13, 124.42, 125.53, 132.12, 134.43, and
155.53 (10, Aromatic C), 151.62(C3), 153.53 (C4), and 168.28
(C6) ppm. MS (DI): Mþ at m/z 750. The other main fragmen-
tation peaks were at m/z 576, 311, 269, 134, and 91. Anal.
(calcd./found in %) for C39H38N6O6S2: C, 62.28/72.5; H, 5.10/
5.28; N, 11.19/11.31; S, 8.54/8.34.
ppm. MS (DI): Mþ at m/z 600. The other main fragmentation
peaks were at m/z 513, 426, 0394, 216, 130, and 91. Anal.
(calcd./found in %) for C30H28N6O4S2: C, 59.98/59.77; H,
4.70/4.56; N, 13.99/13.73; S, 10.68/10.51.
Synthesis of 1,3-bis[4-(20-methylphenyl)-5-carbethoxy meth-
ylmercapto-1,2,4-triazol-3-yl]benzene (13c). m.p. 165–167ꢀC,
Yield 60%. IR (KBr, cmꢁ1): 3429.5, 2971.8, 1742.5, and
1
Synthesis of 1,9-Dibenzena-2,8-(3,5)-1,2,4-triazola-10,14-
dioxa-3,7-dithia-24,84-diphenyl-12-oxo-cyclotetradecaphane
(11). m.p. 172–174ꢀC, Yield: 46%. HRMS: Found Mþ
632.7536; C34H28N6O3S2 requires 632.7545. IR (KBr, cmꢁ1):
3057.4, 2954.0, 1723.7, 1555.3, 1511.1, 1331.1, and 1222.4.
1H NMR (CDCl3): d 2.26 (quintet, 2H, J ¼ 6.5 Hz, H1), 3.41
(t, 4H, J ¼ 6.5 Hz, H2), 4.54(s, 4H, H5) and 6.57–7.64(m,
18H, Aromatic H). 13C NMR (CDCl3): 29.12 (C1), 32.10
(C2), 70.09(C5), 112.28, 125.43, 126.84, 127.33, 128.53,
129.42, 132.32, 134.43, and 155.53 (9, Aromatic C),
151.62(C3), 153.53 (C4), and 173.10(C6) ppm. MS (DI): Mþ
at m/z 632. The other main fragmentation peaks were at m/z
576, 311, 269, 134, and 91. Anal. (calcd./found in %) for
C34H28N6O3S2: C, 64.54/64.36; H, 4.46/4.20; N, 13.28/13.50;
S, 10.13/10.34.
1437.3. H NMR (DMSO-d6): d 1.51 (t, 6H, 2x AOCH2ACH3),
1.85(s, 6H, 2x ArACH3), 3.45 (s, 4H, 2x ASACH2) and 7.24–
7.65 (m, 12H, Aromatic H). 13C NMR (DMSO-d6): 13.79 (2x
AOCH2ACH3) 17.01 (2x ArACH3), 33.49 (2x ASACH2),
52.62(2x AOCH2), 125.98, 126.32, 126.98, 127.44, 128.33,
128.87, 129.32, 130.33, 132.39, and 135.38 (10, Aromatic C),
147.60 (2x ANAC¼¼N), 153.73 (2x ASAC¼¼N), and 167.79
(C¼¼O) ppm. MS (DI): Mþ at m/z 628. The other main frag-
mentation peaks were at m/z 542, 306, 216, 150, 128, and 91.
Anal. (calcd./found in %) for C32H32N6O4S2: C, 61.13/61.33; H,
5.13/5.31; N, 13.37/13.52; S, 10.20/10.58.
Synthesis of 2(1,3)-benzena-14,34-diethyl-4,8-dithia-(1,3)(3,5)-
1,2,4-triazola-cyclooctaphane-6-one (14a). m.p. 215–217ꢀC,
Yield 58%. HRMS: Found Mþ 386.4926; C17H18N6OS2
requires 386.4944. IR (KBr, cmꢁ1): 3429.5, 2971.4, 1742.9,
1
Synthesis of 1,3-bis (4-ethyl-5-mercapto-1,2,4-triazol-3-yl)
benzene (12a). m.p. 170–170ꢀC, Yield 74%. IR (KBr, cmꢁ1):
3100.0, 2933.1, 1623.6, 1545.9, 1501.6, 1277.9, and 1145.9.
1H NMR (DMSO-d6): d 1.51 (t, 6H, J ¼ 7.0 Hz, 2x
ANACH2CH3), 3.78 (quintet, 4H, J ¼ 7.0 Hz, 2x NACH2),
7.44, 7.78, and 8.16 (m, 4H, Aromatic H) and 14.08 (s, 2H,
ASH, D2O exchangeable). 13C NMR (DMSO-d6): 16.37 (2x
ANACH2CH3), 38.97 (2x ANACH2), 125.14, 126.99, 129.32,
and138.83 (4, Aromatic C), 150.22 (2x NAC¼¼N) and 166.97
(2x SAC¼¼N) ppm. MS (DI): Mþ at m/z 332. The other main
fragmentation peaks were at m/z 303, 274, 216, 130, and 91.
Anal. (calcd./found in %) for C14H16N6S2: C, 50.58/50.34; H,
4.85/4.59; N, 25.28/25.39; S, 19.29/19.49.
and 1437.5. H NMR (DMSO-d6): d 1.23 (t, 6H, J ¼ 7.5 Hz,
2x ANACH2CH3), 3.74 (s, 4H, 2x ASACH2), 4.06 (q, 4H, J
¼ 7.5 Hz, 2x ANACH2) and 7.78, 7.83, and 7.87 (m, 4H, Ar-
omatic H). 13C NMR (DMSO-d6): 15.32 (2x ANACH2CH3),
35.25 (2x ASACH2), 40.21 (2x ANACH2), 126.14, 127.74,
129.34, and 130. 57 (4, Aromatic C), 145.84 (2x ANAC¼¼N),
154.68 (2x ASAC¼¼N) and 169.99 (C¼¼O) ppm. MS (DI):
Mþ at m/z 386. The other major fragments were located at m/
z 330, 158, 130, and 91. Anal. (calcd./found in %) for
C17H18N6OS2: C, 52.83/52.53; H, 4.69/4.56; N, 21.74/21.62;
S, 16.59/16.78.
Synthesis of 2(1,3)-benzena-14,34-diphenyl-4,8-dithia-6-oxo-
(1,3)(3,5)-1,2,4-triazola-cyclooctaphane (14b). m.p. 170–172ꢀC,
Yield 62%. HRMS: Found Mþ 482.5790; C25H18N6OS2
requires 482.5803. IR (KBr, cmꢁ1): 3059.5, 1734.9, 1641.2,
Synthesis of 1,3-bis[4-ethyl-5-carbethoxymethyl mercapto-
1,2,4-triazol-3-yl]benzene (13a). m.p. 78–80ꢀC, Yield 65%. IR
(KBr, cmꢁ1): 2982.8, 2933.6, 1761.6, 1648.8, 1467.7, 1305.3,
1
and 1596.8. H NMR (DMSO-d6): d 4.05 (s, 4H, 2x SACH2)
1
and 1174.2. H NMR (CDCl3): d 1.29 (t, 6H, J ¼ 6.5 Hz, 2x
and 7.28–7.78 (m, 14H, Aromatic H). 13C NMR (DMSO-d6):
34.18 (2x ASACH2), 126.96, 127.33, 128.42, 128.98, 130.39,
130.84, 132.39, and 133.33 (8, Aromatic C), 151.73 (2x
ANAC¼¼N), 153.51 (2x ASAC¼¼N), and 169.28 (C¼¼O) ppm.
MS (DI): Mþ at m/z 482. The other major fragments were
located at m/z 426, 292, 158, 130, and 91. Anal. (calcd./found
in %) for C25H18N6OS2: C, 62.22/62.33; H, 3.76/3.64; N,
17.41/17.52; S, 13.29/13.50.
ANACH2CH3), 1.38 (t, 6H, J ¼ 6.5 Hz, 2x AOACH2CH3),
4.13 (q, 4H, J ¼ 6.5 Hz, 2x ANACH2), 4.19 (s, 4H, 2x
ASACH2), 4.24 (q, 4H, J ¼ 6.5 Hz, 2x AOACH2), 7.64,
7.70, and 7.85 (4, Aromatic H). 13C NMR (CDCl3): 13.23 (2x
ANACH2CH3), 15.98 (2x AOACH2CH3), 35.10 (2x
ASACH2), 40.05 (2x ANACH2), 62.20 (2x AOACH2),
127.36, 128.43, 128.53, and 136.12 (4, Aromatic C), 150.00
(2x ANAC¼¼N), 154.55 (2x ASAC¼¼N) and 167.35 (2x
AC¼¼O) ppm. MS (DI): Mþ at m/z 536. The other main frag-
mentation peaks were at m/z 303, 274, 216, 130, and 91. Anal.
(calcd./found in %) for C24H36N6O4S2: C, 53.71/53.5; H, 6.76/
6.60; N, 15.66/15.46; S, 11.95/11.86.
Synthesis of 2(1,3)-benzena-14,34-di(20-methylphenyl)-4,8-
dithia-6-oxo-(1,3)(3,5)-1,2,4-triazola-cyclooctaphane (14c). m.p.
223–225ꢀC, Yield 50%. HRMS: Found Mþ 510.6320;
C
27H22N6OS2 requires 510.6332. IR (KBr, cmꢁ1): 3490.6,
1
2928.8, 1723.3, and 1447.9. H NMR (DMSO-d6): d 1.78 (s,
6H, 2x ArACH3), 4.10 (s, 4H, 2x ASACH2), 7.25–7.61 (m,
12H, Aromatic H). 13C NMR (DMSO-d6): 16.65 (2x
ArACH3), 33.25 (2x ASACH2), 126.04, 126.63, 127.30,
127.98, 128.68, 129.33, 131.34, 132.49, 133.89, and 135.10
(10, Aromatic C), 151.76 (2x ANAC¼¼N), 153.22 (2x
ASAC¼¼N) and 169.17 (C¼¼O) ppm. MS (DI): Mþ at m/z
510. The other major fragments were located at m/z 454,
306, 158, 130, and 91. Anal. (calcd./found in %) for
C27H22N6OS2: C, 63.51/63.39; H, 4.34/4.41; N, 16.46/16.52;
S, 12.56/12.68.
Synthesis of 1,3-bis[4-phenyl-5-carbethoxymethyl mer-
capto-1,2,4-triazol-3-yl]benzene (13b). m.p. 160–162ꢀC, Yield
70%. IR (KBr, cmꢁ1): 2979.3, 2904.5, 1769.8, 1641.8, and
1595.4. 1H NMR (DMSO-d6): d 1.28 (t, 6H, J ¼ 7.0 Hz, 2x
AOCH2CH3) 4.09 (q, 2H, J ¼ 7.0 Hz, 2x AOACH2) 4.23 (s,
2x SACH2) and 7.29–7.58 (m, 14H, Aromatic H). 13C NMR
(DMSO-d6): 14.05 (2x AOCH2CH3), 33.88 (2x SACH2),
61.31 (2x AOACH2), 126.94, 128.34, 128.98, 129.43, 130.43,
132.33, 132.98, and 133.31 (8, Aromatic C), 151.41 (2x
ANAC¼¼N), 153.57 (2x ASAC¼¼N) and 168.02 (2x C¼¼O)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2012
Novel Synthesis of 1,2,4-Triazolophanes and 1,3,4-Oxadiazolophanes: A Dieckmann
Condensation Approach
335
Synthesis of 2(1,3)-benzena-14,34-diethyl-4,8-dithia-6-thio-
(1,3)(3,5)-1,24-triazola-cyclooctaphan (15a). m.p. 268–270ꢀC,
Yield 50%. IR (KBr, cmꢁ1): 2932.5, 1624.9, 1544.5, 1278.5,
and 1145.3. H NMR (DMSO-d6): d 1.17 (t, 6H, J ¼ 7.0 Hz,
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1
2x ANACH2ACH3), 3.34 (s, 4H, 2x ASACH2), 4.09 (q, 4H,
J ¼ 7.0 Hz, 2x ANACH2), 7.79, 7.81, 7.98, and 8.88 (Aro-
matic H). 13C NMR (DMSO-d6): 13.82 (2x ANACH2ACH3),
33.45 (2x ANACH2), 40.44 (2x ASACH2), 127.45, 128.34,
129.49, and 131.33 (4 Aromatic C), 150.74 (2x ANAC¼¼N),
153.45 (2x ASAC¼¼N), and 167.41 (C¼¼S) ppm. MS (DI):
Mþ at m/z 402. The other major fragments were located at m/
z 330, 158, 130, and 91. Anal. (calcd./found in %) for
C17H18N6S3: C, 50.72/50.65; H, 4.51/4.36; N, 20.88/20.67; S,
23.89/23.78.
[8] Chande, M. S.; Mondkar, H. S. J Chem Res 2008, 7, 402.
[9] Chande, M. S.; Puthamane, K. A.; Barve, P. A.; Khanwel-
kar, R. R.; Venkataraman, D. S. J Braz Chem Soc 2008, 19, 42.
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Wiley: New York, 1967; Vol. 15, p 1.
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23, 1708.
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2008, 64, 10009.
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Tetrahedron 2002, 58, 1433.
Synthesis of 2(1,3)-benzena-14,34-diphenyl-4,8-dithia-6-thio-
(1,3)(3,5)-1,24-triazola-cyclooctaphan (15b). m.p. >300ꢀC, Yield
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25, 2509.
1
49%. IR (KBr, cmꢁ1): 3169, 2927, 1595, and 1497. H NMR
(DMSO-d6): d 3.48 (s, 4H, 2x SACH2), 7.24–7.47 (m, 14H,
Aromatic H). 13C NMR (DMSO-d6): 38.68 (2x ASACH2),
126.22, 126.78, 127.59, 128.39, 128.89, 129.44, 130.33–132.21
(8, Aromatic C), 134.14 (2x ANAC¼¼N), 149.62 (2x
ASAC¼¼N), and 168.66 (C¼¼S)ppm. MS (DI): Mþ at m/z 498.
The other major fragments were located at m/z 426, 292, 158,
and 91. Anal. (calcd./found in %) for C25H18N6S3: C, 60.22/
60.11; H, 3.64/3.56; N, 16.85/16.77; S, 19.29/19.40.
[15] Periasamy, M.; Reddy, M. R.; Radhakrishnan, U.; Devasa-
gayaraj, A. J Org Chem 1993, 58, 4997.
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1993, 58, 2369.
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Lett 1990, 31, 6317.
Synthesis of 2(1,3)-benzena-14,34-di(20-methylphenyl-4,8-dithia-
6-thio-(1,3)(3,5)-1,24-triazola-cyclooctaphan (15c). m.p. 243–
245ꢀC, Yield 45%. IR (KBr, cmꢁ1): 3435.6, 2922.5, 1597.2,
1497.8, and 1263.4. 1H NMR (DMSO-d6): d 1.98 (s, 6H, 2x
ArACH3), 3.82(s, 4H, 2x ASACH2), 7.13–7.45 (m, 12H, Aro-
matic H). 13C NMR (DMSO-d6): 17.73 (2x Ar-CH3), 28.27
(2x ASACH2), 126.22, 126.55, 127.32, 127.98, 128.48,
128.84, 129.32, 130.29, 131.38, and 133.22 (10, Aromatic C),
137.18 (2x ANAC¼¼N), 152.34 (2x ASAC¼¼N) and 151.32
(C¼¼S) ppm. MS (DI): Mþ at m/z 526. The other major frag-
ments were located at m/z 454, 306, 158, and 91. Anal.
(calcd./found in %) for C27H22N6S3: C, 61.57/61.64; H, 4.21/
4.30; N, 15.96/15.88; S, 18.26/18.44.
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Acknowledgments. The authors are thankful to the TIFR, IIT,
University of Pune, and Chemistry Department, The Institute of
Science, Mumbai, for scanning the IR, NMR, and mass spectra.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet