Regioselective N-alkylation for the synthesis of novel aminotriazolophanes

Article abstract of DOI:10.1002/hc.20211

Regioselective synthesis of macrocycles, incorporating 3-oxo-4-amino-1,2,4- triazole derivatives, has been achieved by reactions involving N-alkylation, utilizing appropriate 1, ω-dihaloalkanes in the presence of metal hydroxide.

Full text of DOI:10.1002/hc.20211

Heteroatom Chemistry
Volume 17, Number 4, 2006
Regioselective N-alkylation for the Synthesis
of Novel Aminotriazolophanes
M. S. Chande, Meera H. Uchil, and P. A. Barve
Department of Chemistry, The Institute of Science, 15, Madam Cama Road, Mumbai 400 032, India
Received 2 September 2004; revised 29 April 2005
We have recently reported various triazolophane lar-
ABSTRACT: Regioselective synthesis of macrocycles,
iats containing amino side arm [10].
incorporating 3-oxo-4-amino-1,2,4-triazole deriva-
In continuation of our work, we now report
tives, has been achieved by reactions involving
a facile regioselective synthesis of aminotriazolo-
N-alkylation, utilizing appropriate 1,ω-dihaloalkanes
phanes involving N-alkylation.
ꢀ
C
in the presence of metal hydroxide.
2006 Wi-
ley Periodicals, Inc. Heteroatom Chem 17:329–
336, 2006; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20211
RESULTS AND DISCUSSION
In Scheme 1, the starting synthon, 3-oxo-4-amino-
5-mercapto-1,2,4-triazole, 1 was prepared in good
yields from thiocarbohydrazide by its reaction with
carbonoxysuphide [11].
The synthon 1 was treated with 1,2-bis(bro-
momethyl)benzene and bis(iodoethyl)ether in aque-
ous methanol in the presence of metal hydroxide
to afford 1,2-bis[(3-oxo-4-amino-1,2,4-triazol-5-yl)
mercaptomethyl]benzene, 5 and 1,5-bis[(3-oxo-4-
amino-1,2,4-triazol-5-yl) mercaptoethyl]ether 6. 1
was also treated with various 1,ꢀ-dihaloalkanes
to yield 1,ꢀ-bis(3-oxo-4-amino-1,2,4-triazol-5-yl)-
mercaptoalkanes 7a–d.
For compound 5, IR spectrum gave a strong ab-
sorption at 1710 cm−1 for >C O. 1H NMR showed a
singlet at δ 4.38 (S CH2), a singlet at δ 5.30 ( NH2),
a multiplet at δ 7.25–7.39 (aromatic protons), and a
singlet at δ 11.71 ( NH, amido, D2O-exchangeable).
13C NMR showed signals at 30.76 ppm (S CH2), at
127.97–135.32 ppm (aromatic carbons), at 145.01
ppm (>C N), and at 154.64 ppm (>C O).
INTRODUCTION
Crown compounds have generated considerable in-
terest in the past three decades because of their abil-
ity to form stable complexes with a variety of metal
and organic cations and anions [1–5]. They also have
wide applications in phase transfer catalysis [6,7]. In
recent years, various structural changes have been
made to the basic “crown ether” structure in order
to enhance the selective activity of the ligands [8].
Incorporation of heterocyclic subunits provides
rigidity to the macrocycle and assists in increasing
the stability of complexes formed with both metals
and organic cations [8]. The observation that certain
triazoles were capable of inhibiting fog formation [9]
in photographic emulsions and that others were use-
ful as anticonvulsants [9] and herbicides [9] has led
to a renewed attention particularly by the chemical
industry, to simple and fused triazole systems. 1,2,4-
Triazoles also have potent antimicrobial activity [9].
From the above data, the compound 5 was
identified as 1,2-bis(3-oxo-4-amino-1,2,4-triazol-5-
yl) mercaptomethylbenzene.
Correspondence to: M. S. Chande; e-mail: chandems@vsnl.com.
The absence of a peak for SH in 1H NMR,
and the absence of signal for >C S in 13C NMR of
Contract grant sponsor: Mumbai University.
2006 Wiley Periodicals, Inc.
c
ꢀ
329

330 Chande, Uchil, and Barve
SCHEME 1
compound 5, indicated that S-alkylation had taken
place. The singlet for the amido NH proton in the
1H NMR of compound 5, and the signal for carbonyl
carbon of the amido group in the 13C NMR, indicated
that the compound exists in the amido form and not
in the iminol form. The spectra of compounds 6 and
7a–d also led to similar conclusions.
absence of the amido proton ( NH ) peaks, which
were very prominent in the 1H NMR spectra of com-
pounds 5, 6, and 7a–d.
Also, the presence of a distinct peak for NH2
protons in the proton NMR showed that cyclization
did not involve the N NH2 group. The spectral data
of the other aminotriazolophanes synthesized were
in agreement with the above observations.
The intramolecular alkylation, which regioselec-
tively occurs at amido nitrogen, is mainly because
of the template formation due to the presence of
the hexadentate potassium ions where two lig-
ands are water molecules [13a,b]. The reactions
were carried out in large excess of solvent for
ensuring intramolecular cyclization (high-dilution
condition). In Scheme 3, the starting synthons
In Scheme 2, the crown precursors 5, 6, and 7a–
d were reacted with 1,2-bis(bromomethyl)benzene,
2,2ꢁ-diiodoethylether
3 and with various 1,ꢀ-
dihaloalkanes 4 to afford the novel aminotriazolo-
phanes 8–13.
IR spectrum of compound 8a gave a strong ab-
sorption at 1698 cm−1 (>C O). 1H NMR showed
a singlet at δ 4.51(S CH2–), a singlet at 5.19 (N–
CH2–), a singlet at 5.42 ( NH2), and a multiplet at
7.22–7.40 (aromatic protons). 13C NMR gave a sig-
nal at 29.71 ppm (S CH2), 45.75 ppm ( N CH2),
multiple signals at 128.14, 129.51, 130.88, 135.05,
and 135.6 ppm (aromatic carbons), a signal at
144.94 ppm (>C N), and a signal at 153.59 ppm
(>C O).
From the above data, the compound 8a was
identified as 2,6-dithia-14,74-diamino-4(1,2)-9(1,2)-
dibenzena-1(2,5),7(5,2)-di(3-oxo-1,2,4-triazola)-cyclo-
decaphane [12].
The strong absorptions for >C O in IR spectrum
and the signal for >C O in the 13C NMR spectrum
of the compound 8a indicated that N-alkylation had
taken place. This was further confirmed by the clear
1,ꢀ-bis-(4-amino-3-oxo-1,2,4-triazol-5-yl)
alkanes
16a–b were synthesized by fusing 1,ꢀ-dicarboxylic
acids with carbohydrazide in an oil bath at 140◦C
for 4 h. IR spectrum of compound 16b gave a
strong absorption at 1709 cm−1(>C O). 1H NMR
showed a pentet at δ 1.64(CH2 CH2 CH2 CH2),
a triplet at δ 2.47(N C CH2), a singlet at δ 5.1
( NH2), and a singlet at δ 11.26 ( NH). 13C NMR
showed signals at 24.18 and 24.91 (aliphatic
carbons), a signal at 148.36 ppm (>C N), and
at 154.59 ppm (>C O). M+, m/z (%) 254(45),
223(35), 141(55), 127(100), 82(20), 55(30). From
the above data, the compound 16b was identified
as 1,4-bis(4-amino-3-oxo-1,2,4-triazol-5-yl)butane.
Heteroatom Chemistry DOI 10.1002/hc

Regioselective N-alkylation for the Synthesis of Novel Aminotriazolophanes 331
SCHEME 2
The spectra of compound 16a also led to similar
conclusions.
gave signals at 20.02, 24.37, 25.84, 28.53, and 42.83
(aliphatic carbons), a signal at 147.06 (>C N),
and a signal at 153.16 ppm (>C O). M+, m/z (%)
322(40), 306(20), 291(45), 224(10), 154(8), 108(58),
and 82(100). From the above data, the compound
18b was identified as 14,64-diamino-1(2,5),6(2,5)-di-
(3-oxo-1,2,4-triazola)-cycloundecaphane.
The crown precursors 16a,b were reacted with
1,2-bis(bromomethyl)benzene and with various 1,ꢀ-
dihaloalkanes to afford the novel aminotriazolo-
phanes 17a–c and 18a–d.
IR spectrum of compound 18b gave a strong
EXPERIMENTAL
1
absorption at 1695 cm−1 (>C O). H NMR showed
a pentet at δ 1.08 (N CH2 CH2 CH2), a pentet at
δ 1.57 (2 × N CH2 CH2 and 2 × N C CH2 CH2),
a triplet at δ 2.48 (2 × C N CH2), a triplet at 3.68
( N CH2), and a singlet at 5.22 ( NH2). 13C NMR
Melting points were determined on Tempo melting
point apparatus in open capillaries and are
uncorrected. The IR spectra (potassium bromide, ν
in cm−1) were recorded on a Perkin-Elmer 257-FTIR
Heteroatom Chemistry DOI 10.1002/hc

332 Chande, Uchil, and Barve
water and crystallized from dimethylsulfoxide to
give 5. This compound was isolated (2.4 g, 65%)
1
mp 235◦C. IR : ν 1710. H NMR (DMSO-d6) δ 4.38
(s, 2H, S CH2), 5.30 (s, 2H, NH2), 7.25–7.39 (m,
4H, Ar-H), 11.71 (s, 2H, 2 × NH, amido). 13C NMR
(DMSO-d6): δ 30.76 (S CH2), 127.97–135.32 (Ar-C),
145.01 (>C N), and 154.64 ppm (>C O). MS, m/z
(%): M+, 366(25), 234(22), 219(29), 132(98), 104(74).
Elemental analysis for C12H14O2N8S2. MW: 366. Calc:
C 39.34, H 3.82, O 8.74, N 30.60, S 17.48; Found: C
39.36, H 3.83, O 8.75, N 30.61, S 17.47.
Synthesis of 1,2-Bis(3-oxo 4-amino-5-mercapto-
1,2,4-triazol-5-yl) Diethyl Ether, 6
A solution of 1 (2.64 g, 20 mmol), potassium hy-
droxide (1.3 g, 20 mmol in minimum water), 2,2ꢁ-
diiodoethylether 3 (3.26 g, 10 mmol) in 100 mL
methanol was warmed to reflux for 4 h. A white solid
was formed in the reaction mixture in 3 h. This was
collected by filtration, washed with water, and crys-
tallized from dimethylsulfoxide to give 6. This com-
pound was isolated (1.70 g, 51%), mp 205◦C. IR : ν
1710. 1H NMR (DMSO-d6) δ 3.16 (t, 4H, 2 × O CH2),
3.60 (t, 4H, 2 × S CH2), 5.26 (s, 4H, 2 × NH2),
11.63 (s, 2H, 2 × NH, D2O-exchangeable); 13C NMR:
(DMSO-d6): 28.63 ( S CH2), 68.46 ( O CH2),
145.66 (>C N), 154.74 ppm (>C O). MS, m/z (%)
M+334(10), 159(23), 117(100), 105(25). Element.
anal. for C8H14O3N8S2 mw: 366. Calc: C 28.74, H 4.19,
N 33.53, S 19.15; Found C 28.72, H 4.20, N 33.54, S
19.14
General Procedure for Synthesis of 1,ω-Bis(3-
oxo-4-amino-5-mercapto-1,2,4-triazol-5-yl)-
alkanes 7a–d
SCHEME 3
1600 spectrophotometer. 1H NMR spectra (deute-
rochloroform and deuterodimethylsulfoxide, δ in
ppm) were run on a Bruker AMX 500 spectrome-
ter, using trimethylsilane as the internal standard.
Mass spectra (70 eV) were recorded on Shimadzu
QP 2010 GC-MS spectrometer, and the elemental
analyses were carried out at Mumbai University In-
stitute of Chemical Technology, Matunga, Mumbai,
India.
A solution of 1 (2.64 g, 20 mmol), potassium hydrox-
ide (1.3 g, 20 mmol in minimum water), 1,ꢀ-dibromo
alkane 4 (10 mmol) in 100 mL of methanol was
warmed to reflux for 4 h. A white solid was formed
in the reaction mixture in 3 h. This was collected by
filtration, washed with water, dried and crystallized
from dimethylsulfoxide to give 7a–d. The physical
constants and the spectral data of the compounds
7a–d are included in Tables 1 to 3.
Synthesis of 1,2-Bis(3-oxo 4-amino-5-mercapto-
1,2,4-triazol-5-ylmethyl)benzene 5
Synthesis of 2 6-Dithia-14, 74-diamino-4 (1,2)-
9(1,2)-dibenzena-1(2,5),7(5,2)-di(3-oxa-1,2,4
triazola)-cyclodecaphane, 8a
A solution of 1 (2.64 g, 20 mmol), potassium
hydroxide (1.3 g, 20 mmol in minimum water), 1,2
bis(bromomethyl)benzene, 2 (2.64 g, 10 mmol) in
100 mL methanol was warmed to reflux for 4 h. A
white solid was formed in the reaction mixture in
3 h. This was collected by filtration, washed with
A solution of 5 (3.66 g, 10 mmol), potassium hy-
droxide (1.3 g, 20 mmol), and 1,2-bis (bromomethyl)
benzenes 2 (2.64 g, 10 mmol) in 200 mL of 80:20
aqueous methanol was warmed to reflux for 4 h. By
Heteroatom Chemistry DOI 10.1002/hc

Regioselective N-alkylation for the Synthesis of Novel Aminotriazolophanes 333
TABLE 1 Physical and Chemical Characteristics and Data Analysis
Found/Calculated (%)
Molecular
Formula
No.
C
H
N
S
mp ( ◦C)
Yield (%)
7a
C6H10O2N8S2
C7H12O2N8S2
C8H14O2N8S2
C9H16O2N8S2
24.81/24.82
27.62/27.63
30.16/30.18
32.54/32.53
44.31/44.32
45.72/45.70
46.96/46.99
34.88/34.87
36.85/36.86
42.84/42.85
32.72/32.72
34.86/34.87
36.88/36.86
38.72/38.70
44.33/44.32
38.72/38.70
40.42/40.40
45.73/45.70
41.97/41.98
46.98/46.99
31.88/31.86
37.85/37.79
42.88/42.85
44.86/44.89
52.80/52.73
46.70/46.74
48.45/48.44
55.12/55.08
53.91/53.92
3.44/3.47
3.97/3.97
4.41/4.43
4.83/4.85
4.47/4.46
4.79/4.79
5.09/5.10
4.67/4.68
5.03/5.06
4.12/4.11
4.27/4.27
4.67/4.68
5.07/5.06
5.39/5.41
4.47/4.46
5.42/5.41
5.73/5.74
4.78/4.79
6.06/6.04
5.11/5.10
4.44/4.46
5.51/5.50
5.68/5.75
6.13/6.16
7.68/7.74
6.48/6.50
6.82/6.83
8.18/8.22
5.65/5.66
38.63/38.62
36.84/36.82
10.07/10.19
33.69/33.71
25.56/25.57
26.67/26.65
25.78/25.79
32.54/32.53
31.29/31.26
28.54/28.55
33.92/33.92
32.54/32.53
31.55/31.56
30.11/30.08
27.55/27.57
30.09/30.08
28.98/28.99
26.64/26.65
27.96/27.98
25.80/25.79
49.53/49.55
44.10/44.07
40.10/39.98
38.05/38.07
30.70/30.75
36.4036.34/
–
22.08/22.09
21.06/21.07
20.18/20.12
19.21/19.29
15.77/15.78
15.23/15.25
14.76/14.76
18.59/18.62
17.86/17.89
16.33/16.34
19.41/19.41
18.62/18.62
17.89/17.89
17.21/17.22
15.78/15.78
17.21/17.22
16.62/16.59
15.26/15.25
16.01/16.01
14.76/14.76
–
263
222
239
222
256
267
285
285
255
241
245
248
279
271
247
272
255
285
259
265
¿ 300
¿ 300
¿ 300
¿ 300
275
¿ 300
270
56
52
57
62
23
28
30
31
22
30
32
35
31
33
30
25
29
26
27
21
50
40
22
25
28
20
21
28
24
7b
7c
7d
8b
8c
8d
C
15H18O2N8S2
C16 20O2N8S2
17H22O2N8S2
10H16O2N8S2
11H18O2N8S2
14H16O2N8S2
H
C
C
C
C
10a
10b
10c
11a
11b
11c
11d
11e
12a
12b
12c
13a
13b
16a
16b
17a
17b
17c
18a
18b
18c
18d
C9H14O2N8S2
10H16O2N8S2
C
C11H18O2N8S2
C12H20O2N8S2
C
C
C
C
C
C
15H18O2N8S2
12H20O2N8S2
13H22O2N8S2
16H20O2N8S2
14H24O2N8S2
17H22O2N8S2
C6H10O2N8
C8H14O2N8
–
C
C
10H16O2N8
11H18O2N8
H O2N8
–
–
–
–
–
–
C16 28
12H20O2N8
C13 22O2N8
18H32O2N8
C16 20O2N8
C
H
C
28.55/28.55
31.48/31.44
H
concentrating the reaction mixture to 50%, a crys-
talline white solid was formed. This was collected by
filtration and washed carefully with a dilute solution
of potassium hydroxide to dissolve any polymeric
material that may have precipitated out. The solid
was then washed well with water, and crystallized
from dimethylsulfoxide to give 8a. This compound
was isolated (1.35 g, 29%). mp 269◦C. IR : ν 1698
(>C O), 1H NMR (DMSO-d6) δ 4.51 (s, 2H, S CH2 ),
5.19 (s, 2H, N CH2 ), 5.42 (s, 2H, NH2), 7.22–
7.40 (m, 8H, Ar-H). 13C NMR: (DMSO-d6): 29.71
( S CH2), 45.75 ( N CH2), 128.14, 129.51, 130.88,
135.05, and 135.6 ppm (Ar-C), 144.94 (>C N) 153.59
ppm (>C O). MS, m/z (%). M+ 468(11), 168(18),
135(42), 1004(35), 41(100). Elemental analysis for
C20H20O2N8S2.mw: 468; Calc C 51.28, H 4.27, N
23.93, S 13.67; Found C 51.27, H 4.28, N 23.95,
S 13.65.
(10 mmol) in 200 mL of 80:20 aqueous methanol was
warmed to reflux for 4 h. By concentrating the reac-
tion mixture to 50%, a crystalline white solid was
formed. This was collected by filtration and washed
carefully with a diluted solution of potassium hy-
droxide to dissolve any polymeric material that may
have precipitated out. The solid was then washed
well with water, and crystallized from dimethylsul-
foxide to give 8b–d. The physical constants and the
spectral data of the compounds 8b–d are included in
Table 1.
Synthesis of 2,8-Dithia-14, 94-diamino-5-oxa-1-
(2,5),9(5,2)-di(3-oxa-1,2,4-triazola)-cyclotetra-
decaphane 9
A solution of 6 (3.34 g, 10 mmol), potassium hy-
droxide (1.3 g, 20 mmol), 1, 5, ω-dibromo pentane
4 (10 mmol) in 200 mL of 80:20 aqueous methanol
were warmed to reflux for 4 h. By concentrating the
reaction mixture to 50%, a crystalline white solid
was formed. This was collected by filtration and
washed carefully with a diluted solution of potas-
sium hydroxide to dissolve any polymeric mate-
rial that may have precipitated out. The solid was
Synthesis of 2,6-Dithia-14, 74-diamino-4(1,2)-
benzena-1(2,5),7(5,2)-di(3-oxa-1,2,4-triazola)-
cyclodecaphanes 8b–d
A solution of 5 (3.66 g, 10 mmol), potassium hy-
droxide (1.3 g, 20 mmol), 1,ꢀ-dibromo alkane 4
Heteroatom Chemistry DOI 10.1002/hc

334 Chande, Uchil, and Barve
TABLE 2 21H NMR Data
7a
7b
δ: 3.26, (s, 4H, S CH2), 5.24 (s, 4H, 2× NH2), 11.62 (s, 2H, 2× NH, D2O-exchangeable
2.015, (p, 2H, S CH2 CH2 ), 3.08 (t, 4H, 2× S CH2), 5.26 (s, 4H, 2× NH2), 11.63
(s, 2H, 2× NH, D2O-exchangeable
7c
1.69 (p, 4H, S CH2 CH2 ), 2.95 (t, 4H, S CH2) 5.21 (s, 4H, 2× NH2), 11.63 (s, 2H,
2× NH, D2O-exchangeable
7d
8b
1.46 (p, 2H, S CH2 CH2 CH2), 1.65 (p, 4H, 2× S CH2 CH2), 2.97 (t, 4H, 2× S CH2), 5.23 (s, 4H,
2× NH2), 11.61 (s, 2H, 2× NH, D2O-exchangeable
ꢁ
ꢁ
2.18 (p, 2H, N CH2 CH2 J = 5.5 Hz), 3.68 (t, 4H, 2× N CH2 J = 5.5 Hz), 4.39 (s, 4H, 2 S CH2) 5.31
(s, 4H, 2× NH2)7.28 7.38 (m, 4H, Ar-H)
ꢁ
ꢁ
8c
1.41 (p, 4H, N CH2 CH2 J = 5.5 Hz), 2.15 (t, 4H, 2× N CH2 J = 5.5 Hz), 4.19 (s, 4H,
2× S CH2), 5.25 (s, 4H, 2× NH2), 7.22 7.45 (m, 4H, Ar-H)
8d
10a
10b
δ 1.24 (p, 2H, N CH2 CH2 CH2, J = 6.5 Hz), 1.63 (p, 4H, 2× N CH2 CH2, J = 6.5 Hz), 3.70 (t, 4H,
ꢁ
2× N CH2 J = 6.5 Hz), 4.38 (s, 4H, 2× S CH2), 5.41 (s, 4H, 2× NH2), 7.34 7.45 (m, 4H, Ar-H)
ꢁ
1.52 (p, 4H, 2× N CH2 CH2 J = 6.5 Hz), 3.28 (s, 4H, 2× S CH2), 3.58 (t, 4H, 2× N CH2, J = 6.5 Hz),
5.38 (s, 4H, 2× NH2)
ꢁ
1.40 (p, 2H, N CH2 CH2 CH2 J = 6.5 Hz), 1.63 (p, 4H, 2× N CH2 CH2, J = 6.5 Hz), 3.31 (s, 4H, 2×
S CH2), 3.67 (t, 4H, 2× N CH2, J = 6.5 Hz), 5.35 (s, 4H, 2× NH2)
10c
11a
2.99 (s, 4H, 2× S CH2), 4.89 (s, 4H, 2× N CH2), 5.40 (s, 4H, 2× NH2), 7.28 7.31 (m, 4H, Ar-H)
ꢁ
2.03 (p, 2H, S CH2 , J = 7 Hz), 3.09 (t, 4H, 2× S CH2 J = 7 Hz), 3.33 (s, 4H, 2× N CH2), 5.28
(s, 4H, 2× NH2)
ꢁ
11b
11c
11d
2.24 (p, 2H, S CH2 , J = 7 Hz), 2.35 (p, 2H, N CH2 CH2 J = 6.5 Hz), 3.18 (t, 4H, 2× S CH2, J = 7
ꢁ
Hz), 3.89 (t, 4H, 2× N CH2 , J = 6.5 Hz), 4.36 (s, 4H, 2× N NH2)
ꢁ
ꢁ
δ 1.58 (p, 4H, N CH2 CH2 J = 6.5 Hz), 2.19 (p, 2H, S CH2 CH2 J = 7 Hz), 2.95 (t, 4H,
2× S CH2, J = 7 Hz), 3.66 (t, 4H, 2× N CH2, J = 6.5 Hz), 5.22 (s, 4H, 2× NH2)
ꢁ
1.20 (p, 2H, N CH2 CH2 , J = 5.5 Hz), 1.54 (p, 4H, N CH2 CH2 J =5.5 Hz), 1.96 (p, 2H,
S CH2 CH2, J = 6.5 Hz), 2.94 (p, 4H, S CH2, J = 6.5 Hz), 3.61 (t, 4H, N CH2, J = 5.5 Hz),
5.31 (s, 4H, 2× NH2)
11e
12a
12b
δ 1.94 (p, 2H, S CH2 , J = 7 Hz), 2.94 (t, 4H, 2× S CH2, J = 7 Hz), 4.89 (s, 4H, 2× N CH2), 5.48
(s, 4H, 2× N NH2), 7.24 7.35 (m, 4H, Ar-H)
1.53 (p, 4H, 2× N CH2 CH2, J = 5.5 Hz), 1.64 (p, 4H, 2× S CH2 CH2, J = 6.5 Hz), 2.98 (t, 4H, 2×
S CH2, J = 6.5 Hz), 3.61 (t, 4H, 2× N CH2, J = 5.5 Hz), 5.36 (s, 4H, 2× NH2)
1.20 (p, 2H, N CH2 CH2 CH2, J = 5.5 Hz), 1.57 (p, 4H, 2× N CH2 CH2, J = 5.5 Hz), 1.70 (p, 4H, 2×
S CH2 CH, J = 6.5 Hz), 2.96 (t, 4H, 2× S CH2, J = 6.5 Hz), 3.65 (t, 4H,
2× N CH2, J = 5.5 Hz), 5.30 (s, 4H, 2× NH2)
12c
13a
1.59 (p, 4H, 2× S CH2 CH2, J = 6.5 Hz), 2.89 (t, 4H, 2× S CH2, J = 6.5 Hz), 5.08 (s, 4H, 2×
N CH2), 5.38 (s, 4H, 2× NH2), 7.11 7.23 (m, 4H, Ar-H)
1.16 (p, 2H, N CH2 CH2 CH2, J = 7 Hz), 1.42 (p, 2H, S CH2 CH2, J = 7 Hz), 1.60 (p, 4H,
2× N CH2 CH2, J = 7 Hz), 1.66 (p, 4H, S CH2 CH2, J = 7 Hz), 2.92 (t, 4H, 2× S CH2, J = 7 Hz),
3.59 (t, 4H, 2× N CH2, J = 7 Hz), 5.30 (s, 4H, 2× NH2)
13b
16a
16b
17a
17b
17c
18a
18b
1.48 (p, 2H, S CH2 CH2 CH2, J = 6.5 Hz), 1.68 (p, 2H, S CH2 CH2, J = 6.5 Hz), 2.93 (t, 4H, 2 × S ,
J = 6.5 Hz), 5.17 (s, 4H, 2 × N CH2 ), 5.43 (s, 4H, 2 × N NH2), 7.07 7.26 (m, 4H, Ar-H)
1H NMR (DMSO-d6): δ 2.82 (t, 4H, 2× CH2 CH2), 5.15 (s, 4H, 2× N NH2), 11.36 (s, 2H,
2× NH D2O exchangeable
1H NMR (500 MHz/DMSO-d6): δ 1.64 (p, 4H, CH2 CH2 ), 2.47 (t, 2H, C N CH2), 5.10 (s, 4H, 2×
N NH2), 11.26 (s, 2H, 2× NH)
1H NMR (DMSO-d6): δ 1.21 (p, 4H, 2× CH2 CH2), 2.82 (t, 4H, 2× N C CH2), 3.41 (t, 4H, 2× N CH2),
5.33 (s, 4H, 2× N NH2)
1H NMR (DMSO-d6): δ 0.99 (p, 2H, N CH2 CH2 CH2), 1.49 (p, 4H, 2× N CH2 CH2), 2.83 (t, 4H, 2×
N C CH2), 3.43 (t, 4H, 2× N CH2), 5.32 (s, 4H, 2× N NH2)
1H NMR (DMSO-d6): pentets at δ 1.40, 1.53, 1.63, and 1.73 (aliphatic-H), 3.01 (t, 4H, 2× N C CH2),
3.75 (t, 4H, 2× N CH2), 5.42 (s, 4H, 2× N NH2)
1H NMR (DMSO-d6): δ 1.53 (p, 4H, 2× N CH2 CH2), 1.60 (p, 4H, 2× C N CH2 CH2), 2.46 (t, 4H, 2×
N C CH2 CH2), 3.53 (t, 4H, 2× N CH2), 5.21 (s, 4H, 2× N NH2)
1H NMR (500 MHz/ DMSO-d6): δ 1.08 (p, 2H, N CH2 CH2 CH2), 1.57 (p, 8H,
2× N CH2 CH2 and 2× C N CH2 CH2), 2.48 (t, 4H, 2× C N CH2), 3.61 (t, 4H, 2× N CH2),
5.22 (s, 4H, 2× N NH2)
18c
18d
1H NMR (500 MHz/DMSO-d6): δ 1.08 (p, 2H, N CH2 CH2 CH2), 1.57 (p, 8H, 2× N CH2 CH2 and 2×
C N CH2 CH2), 2.48 (t, 4H, 2× C N CH2), 3.61 (t, 4H, 2× N CH2), 5.22 (s, 4H, 2× N NH2)
1H NMR (DMSO-d6) δ: 1.79 (p, 4H, 2× N C CH2 CH2), 2.67 (t, 4H, 2× N C CH2), 3.50 (t, 4H, 2×
N CH2), 5.43 (s, 4H, 2× N NH2), 7.20 7.58 (m, 4H, Ar-H)
Heteroatom Chemistry DOI 10.1002/hc

Regioselective N-alkylation for the Synthesis of Novel Aminotriazolophanes 335
TABLE 3 13C NMR (DMSO-d6.) Data
1
152.53 (C-3, ¿ C O); 167.33 (C-5, ¿ C S)
28.43 and 29.17 (aliphatic C), 145.91 (¿ C N), 155.15 ppm (¿ C O)
27.13, 28.35, 28.87 (aliphatic C), 145.75 (¿ C N), 154.72 ppm (¿ C O)
23.56, 27.58, 30.65, and 45.53 (aliphatic C), 128.59, 130.89, 134.60 (aromatic C), 144.18 (¿ C N),
153.01 ppm (¿ C O)
7b
7d
8d
10b
10c
23.93, 28.31,31.00, and 44.78 (aliphatic C), 143.72 (¿ C N), 153.41 ppm (¿ C O)
31.53 (S CH2), 45.51 (N CH2), 128.25, 130.51, and 135.99 (aromatic carbons), 143.92 (¿ C N),
153.57 ppm (¿ C O)
11a
11b
12c
14.59, 27.86, 28.64 (aliphatic carbons), 145.46 (¿ C N), 154.66 ppm (¿ C O)
26.58, 27.37, 28.22, and 43.16 (aliphatic carbons), 142.79 (¿ C N), 153.11 ppm (¿ C O)
28.55, 29.03, 46.12 (aliphatic carbons), 128.36, 129.43, and 135.67 (aromatic C), 145.69 (¿ C N),
154.14 ppm (¿ C O)
13a
13b
22.85, 26.42, 27.62, 28.03, 45.15 (aliphatic carbons), 144.28 (¿ C N), 153.09 ppm (¿ C O)
26.63, 27.14, 27.60, 46.38 (aliphatic carbons), 128.14, 128.61, and 135.16 (aromatic C), 145.98 (¿ C N),
153.83 ppm (¿ C O)
16a
16b
21.20 (N C CH2 ), 147.47 (¿ C N), and 154.62 ppm (¿ C O)
13C NMR (DMSO-d6.): 24.18 (2× CH2 CH2), 24.91 (2× ¿ C N CH2) 148.36 (C N) and 154.59 ppm
(¿ C O)
17c
18b
18c
18d
13C NMR (DMSO-d6): 21.21, 25.85, 28.47, 28.79, 32.23, 44.62, (aliph-C), 146.03 (¿ C N), 152.90 ppm
(¿ C O)
13C NMR (solid state NMR): 20.02 (N CH2 CH2 CH2), 24.37 (2× C N CH2 CH2), 25.84 (2×
C N CH2), 28.53 (2× N CH2 CH2), 42.83 (2× N CH2), 147.06 (2× ¿ C N), 153.16 ppm (2× ¿ C O)
13C NMR (DMSO-d6): 24.58, 25.66, 26.49, 28.68, 29.61 (aliphatic carbons), 32.78 (N C C CH2), 34.02
(N C CH2), 147.40 (¿ C N), and 153.78 ppm (¿ C O)
13C NMR (DMSO-d6): 25.14 (N C CH2 CH2), 29.66 (N C C CH2), 46.04(N C Ar), 128.22, 129.30,
135.14 (aromatic carbons), 145.28 (¿ C N), and 153.55 ppm (¿ C O)
then washed well with water, and crystallized from
dimethylsulfoxide to give 9.
ide to dissolve any polymeric material that may have
precipitated out. The solid was then washed well
with water, and crystallized from dimethylsulfoxide
to give compounds 10a–c, 11a–e, 12a–c, and 13a,b.
The physical constants and the spectral data of the
compounds 10a–c, 11a–e, 12a–c, and 13a,b are in-
cluded in Table 1.
This compound was isolated (0.64 g, 16%) mp
276◦C. IR : ν 1698 (>C O). 1H NMR (DMSO-d6)
δ 1.18 (p, 2H, N CH2 CH2 CH2, J = 6.5 Hz),
1.57 (p, 4H, 2 × N CH2 CH2, J = 6.5 Hz), 3.08 (t,
4H, 2 × S CH2, J = 7 Hz), 3.61 (t, 4H, 2× N ,
J = 6.5 Hz), 4.32 (t, 4H, 2 × O CH2, J = 6 Hz),
5.34 (s, 4H, 2 × NH2); MS, m/z (%) M+ 402(100),
240(41), 159(60), 91(115), 69(29). Elemental analy-
sis for C13H22O3N8S2, mw: 402; Calcd C 38.81, H 5.47,
N 27.86, S 15.92; Found C 38.79, H 5.51, N 27.84,
S 15.93.
General Procedure for the Synthesis of
1,ω-Bis(4-amino-5-oxo-1, 2,4-triazol-3-yl)
Alkanes 16a–b
Aliphatic dicarboxylic acids (10 mmol) and carbohy-
drazide (2 ommol) were mixed properly. The mixture
was heated at 140◦C in oil bath for 4 h. Water (50 mL)
was added to the sticky mass and was kept overnight.
A white solid was formed and was filtered, washed
with water, and dried.
General Procedure for the Synthesis of
2,ω-Dithia-14,74-diamino-4(1,2)-9(1,2)-
dibenzena-1(2,5),7(5,2)-di(3-oxa-1,2,4-triazola)-
cyclodecaphanes, 10a–c, 11a–e, 12a–c, and
13a,b
General Procedure for the Synthesis of 14,
ω4-Diamino-1(1,3),ω-(1,3)-di-(5-oxa-1,2,4-
triazola)-cyclophanes 17a–c, 18a–d
A solution of 7a–d (10 mmol), potassium hydrox-
ide (1.3 g, 20 mmol), and 1,2-bis(bromomethyl) ben-
zene 2 (2.64 g, 10 mmol) or 1,ꢀ-dibromo alkane 4
(10 mmol) in 200 mL of 80:20 aqueous methanol was
warmed to reflux for 4 h. By concentrating the reac-
tion mixture to 50%, a crystalline white solid was
formed. This was collected by filtration and washed
carefully with a dilute solution of potassium hydrox-
A solution of 16a (10 mmol), potassium hydroxide
(1.3 g, 20 mmol), 1,ꢀ-dibromo alkane (10 mmol), and
aqueous methanol (80:20, 200 mL) was refluxed to-
gether in a round-bottomed flask for 14 h. By con-
centrating the reaction mixture, a white solid was
Heteroatom Chemistry DOI 10.1002/hc

336 Chande, Uchil, and Barve
[5] Bradshaw, J. S.; Izatt, R. M. Acc Chem Res 1997, 30,
338.
[6] Newkome, G. R.; Traynham, J. G.; Baker, G. R. In:
Compendium of Heterocyclic Compounds; Katritzky
A. R. (Ed.); Vol. 5, p. 763.
[7] Stark, C. M.; Liotta, C.; Halpern, M. (Eds.). Phase
Transfer Catalysis, Fundamentals, Applications and
Industrial Perspective; Chapman and Hall: New York,
1994.
formed. This was filtered and washed carefully with
a diluted solution of potassium hydroxide to dissolve
any polymeric material that may have precipitated
out. The solid was then washed well with water and
crystallized from DMF.
ACKNOWLEDGMENTS
[8] Bradshaw, J. S.; Izzat, R. M.; Bordunov, A. V.; Zhu, C.
Y.; Hathaway, J. K. In Comprehensive Supramolec-
ular Chemistry; Gokel, G. W. (Ed.); Pergamon:
New York, 1996; Vol. 1, p. 35.
[9] Potts, K. T. Chem Rev 1961, 61, 88, 87.
[10] Chande, M. S.; Athalye, S. S.; Synth Commun 1999,
29(10), 1711–1717.
The help rendered by RSIC, IIT, and TIFR, Depart-
ment of Chemistry, University of Pune, and Depart-
ment of Chemistry, Institute of Science, Mumbai is
gratefully acknowledged.
[11] Chande, M. S.; Uchil M. H. (Communicated).
[12] Nomenclature as per the following: (a) Powell, W. H.
Pure Appl Chem. 1998, 70, 1513–1545; (b) Favre, H.
A.; Hellwinkel, D.; Powel, W. H.; Smith, H. A. Pure
Appl Chem 74, 2002, 809–834.
REFERENCES
[1] Graf, E.; Lehn, J. M. Helv Chim Acta 1981, 64, 1040.
[2] Dietrich, B.; Hosseini, M. W.; Lehn, J. M.; Session, R.
B. Helv Chim Acta 1983, 66, 1262.
[13] (a) Bush, D. H. Rec Chem Prog 1965, 107, 25;
(b) Bush, D. H.; Lindoy, L. H. Preparative In-
organic Reactions; Interscience: New York, 1971;
Vol. VI.
[3] Hosseini, M. W; Lehn, J. M.; Mertes, M. P. Helv Chim
Acta 1983, 66, 2444.
[4] Kumar, A.; Mageswaran, S.; Sutherland, I. O. Tetra-
hedron 1986, 42, 3291.
Heteroatom Chemistry DOI 10.1002/hc