Synthesis and?antibacterial activity of?various substituted s-triazines

Article abstract of DOI:10.1016/j.ejmech.2006.05.013

Series of substituted-s-triazines (1-22) were synthesized and evaluated for their in vitro antibacterial activity against six representative Gram-positive and Gram-negative bacterial strains. Many compounds have displayed comparable antibacterial activity

Full text of DOI:10.1016/j.ejmech.2006.05.013

European Journal of Medicinal Chemistry 41 (2006) 1240–1246
http://france.elsevier.com/direct/ejmech
Original article
Synthesis and antibacterial activity of various substituted s-triazines
a,b
a
b,
c
*
K. Srinivas , U. Srinivas , K. Bhanuprakash , K. Harakishore
c,
a,
*
*
U.S.N. Murthy , V. Jayathirtha Rao
a
Organic Chemistry Division II, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
b
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
c
Biology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India
Revised and accepted 25 May 2006
Available online 11 July 2006
Abstract
Series of substituted-s-triazines (1–22) were synthesized and evaluated for their in vitro antibacterial activity against six representative Gram-
positive and Gram-negative bacterial strains. Many compounds have displayed comparable antibacterial activity against Bacillus sphaericus and
significantly active against other tested organisms with reference to streptomycin.
©
2006 Elsevier Masson SAS. All rights reserved.
Keywords: s-Triazine derivatives; Synthesis; Antibacterial activity; Antifungal activity
1
. Introduction
report the synthesis and antibacterial activity of a variety of s-
triazine derivatives.
The rapid development of pathogen resistance to most of the
known antibiotics is becoming a serious health problem [1–3].
Many groups have been working in solving the antibacterial
resistance problems [4–11]. One possible long-term solution
is the development of agents that act on unexploited antibacter-
ial targets [11]. In view of the above, the design and synthesis
of effective and potent antimicrobials is an area of immense
significance for medicinal chemists [1–11]. In this context, s-
triazine derivatives have received considerable attention due to
its potent biological activity such as anti-protozoals [12], antic-
ancer [13], estrogen receptor modulators [14], antimalarials
2. Chemistry
The compounds 1–22 were synthesized to understand the
role of mono, di and tri-substitution, 4-substituted benzyloxy,
4-imidazoloaniline, chiralbenzylamine and styryl groups on
triazine moiety towards antibacterial activity. Synthetic meth-
ods adopted for making compounds 1–22 are illustrated in
Schemes 1–3. Synthesis of s-triazine (cyanuric acid) deriva-
tives 1–5 was performed by means of nucleophilic displace-
ment of chlorine atoms of cyanuric chloride (23). According
to this method compounds 1–5 were obtained by treating two
equivalents of benzyl alcohol derivatives (24–28) with cyanu-
[
15,16], Cyclin-dependent kinase inhibitors [17] and antivirals
[
18]. It has been reported that s-triazine derivatives possess
potent antimicrobial activity [19–23]. Besides, many of the
imidazole containing compounds exhibited the antibacterial
activities [24–26]. Our undiminished interest in this area is to
design and synthesize diverse biologically active heterocyclic
compounds [19,27]. As part of our continuous effort, here we
*
Corresponding authors.
E-mail address: jrao@iict.res.in (V. Jayathirtha Rao).
Scheme 1.
0223-5234/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2006.05.013

K. Srinivas et al. / European Journal of Medicinal Chemistry 41 (2006) 1240–1246
1241
ized by spectroscopic data as NMR, mass, IR and elemental
analysis.
3. Pharmacology
3.1. Antibacterial activity
The in vitro antibacterial screening of all the compounds
were evaluated against selected (Table 1) Gram-positive organ-
isms viz. Bacillus subtilis (MTCC 441), Bacillus sphaericus
(
MTCC 11) Staphylococcus aureus (MTCC 96) and three
Gram-negative organisms viz. Chromobacterium violaceum
MTCC 2656), Klebseilla aerogenes (MTCC 39) and Pseudo-
Scheme 2.
(
monas aeruginosa (MTCC 741) by broth dilution method
recommended by National Committee for Clinical Laboratory
(NCCL) standards [33].
4. Results and discussion
The minimum inhibitory concentration (MIC) was deter-
mined for each compound along with streptomycin as standard
control and the results are presented in Table 1. The MIC
values of four series of s-triazine derivatives (Fig. 1 and
Table 1) against tested organisms displayed significant activity
with a degree of variation. It is found that compounds 5 and 21
displayed substantial activity against B. subtilis and remaining
compounds are significantly active. s-Triazines 2, 6, 9, 10, 18
and 22 are equipotent against B. sphaericus compared to refer-
ence compound. Rest of the compounds have exhibited signif-
icant to substantial activity against the same strain. Substantial
activity is achieved in case of compounds 4, 18, 21 and 22
against S. aureus and the remaining compounds are signifi-
cantly active against the same species. All the s-triazine deri-
vatives have exhibited significant to moderate activity against
Gram-negative bacteria. Derivatives 7, 10, 15, 17 and 22 have
exhibited substantial activity against C. violaceum. Decreased
activity is observed in case of K. aerogenes with all the s-tria-
zines. It is obvious from the structure-activity profile of substi-
tuted s-triazines; a small structural variation may induce an
effect on antibacterial activity. By observing the antibacterial
activities of all the derivatives, it is interesting to note that
the dibenzyloxy s-triazine derivatives 1–5 have shown substan-
tial antibacterial activity against B. sphaericus and moderately
active against all the remaining strains. 4-Chlorobenzyloxy
triazine, 5 exhibited significant activity against B. subtilis and
moderately active against B. sphaericus. Slight decreased
activity was observed by substituting the chlorine with fluorine
group in compound 4, except methyl derivative 2 in this series
has shown comparable activity against B. sphaericus. Further
diminished activity is demonstrated in compounds 1 and 3, by
replacing the fluorine with hydrogen and methoxy groups,
respectively. Imidazole substituted s-triazines 6, 9 and 10
were equipotent against B. sphaericus and moderately active
against C. violaceum. Remaining s-triazine derivatives in this
series, compounds 7, 8 and 11 displayed least activity against
all the tested organisms. Decreased antibacterial activity was
Scheme 3.
ric chloride in the presence of base (Scheme 1). Another new
series of compounds 6–11 were synthesized (Scheme 2) in
multiple steps via intermediates 34–35, which were obtained
by a procedure starting with the condensation of benzil (29)
with p-nitrobenzaldehyde (30) to afford 31 [28]. N-alkylation
of 31 with alkyl iodide in the presence of base gave 32–33.
Further reduction of nitro group of 32–33 with Pd/C and
hydrazine hydrate yielded 34–35 [29]. Treatment of cyanuric
chloride (23) with variable amounts of 34–35 in the presence
of base gave 6–11. Compounds 12–14 were synthesized
(
Scheme 3) by allowing reaction between different molar ratios
of cyanuric chloride (23) and R-(+)-α-methyl benzylamine (36)
in the presence of K CO and 18-Crown-6 [30,31]. Com-
2
3
pounds 15–22 were prepared as per the reported procedure
32]. All the synthesized compounds were purified by column
chromatography followed by recrystallization and character-
[

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K. Srinivas et al. / European Journal of Medicinal Chemistry 41 (2006) 1240–1246
Table 1
In vitro antibacterial activity of substituted s-triazines (1–22)
–1
Compound number
MIC, μg ml
Gram-positive organism
Gram-negative organism
B. subtilis
25
25
50
25
12.5
25
25
50
25
25
50
50
50
25
25
25
25
B. sphaericus
25
12.5
25
50
50
12.5
25
S. aureus
25
25
50
12.5
25
25
25
25
50
50
50
25
25
25
25
25
25
C. violaceum
25
25
50
25
25
25
25
12.5
25
12.5
25
25
25
50
12.5
25
12.5
50
25
50
K. aerogenes
50
50
25
12.5
12.5
50
25
50
50
25
50
50
50
25
25
25
P. aeruginosa
1
2
3
4
5
6
7
8
9
1
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
> 250
3.125
25
12.5
12.5
25
50
50
25
25
25
25
12.5
25
25
25
12.5
12.5
0
1
1
1
1
1
1
1
1
1
1
2
2
2
2
3
4
5
6
7
8
9
0
1
2
25
12.5
25
25
25
50
25
25
12.5
25
12.5
50
50
12.5
12.5
6.25
25
12.5
3.125
50
1.562
Streptomycin
6.25
●
Negative control (acetone).
Fig. 1.

K. Srinivas et al. / European Journal of Medicinal Chemistry 41 (2006) 1240–1246
1243
Fig. 2.
encountered for compounds 12–14 where chlorines were
replaced in cyanuric chloride with 1-phenyl ethylamino
group, respectively. Compounds 15–22 exerted significant
antibacterial activity against tested Gram-positive and moderate
activity against Gram-negative bacterial strains. Compounds
with chloro substitution at para position, 18 and 22 exhibited
equivalent activity with the standard drug streptomycin against
B. sphaericus and significantly active against S. aereus and
moderately active against the remaining tested organisms. In
case of fluoro derivatives, 17 and 21, decrease in the antibac-
terial activity was observed compared to chloro derivatives.
Rest of the compounds in this series (15, 16, 19 and 20) dis-
played moderate activity.
Moreover, by changing the substitution pattern in s-triazine
derivatives may influence the antibacterial activity. The most
active trisubstituted s-triazines derivatives (i–iii) previously
reported by us [19] are given in Fig. 2. The di-substituted ben-
zyloxy s-triazine derivatives exhibited a slightly lower antibac-
terial activity than the tri-substituted benzyloxy s-triazines
22 showed significant activities against tested Gram-positive
organisms and comparable activity towards B. sphaericus
with respect to streptomycin as standard. Derivatives with
chloro substitution in styryl s-triazines 18 and 22 demonstrated
comparable and significant activity against B. sphaericus and
S. aureus. In overall, trisubstituted s-triazines are more active
than the mono and disubstituted s-triazines.
6. Experimental protocols
All the reagents were A.R. grade and used without further
purification. Melting points were determined on a Thomas
1
Hoover melting point apparatus and are uncorrected.
H
NMR spectra were recorded on Gemini (200 MHz) spectro-
13
meter and C NMR spectra on Bruker Avance (75 MHz) spec-
trometer in CDCl and/or DMSO-d using TMS as internal
3
6
standard. Mass spectra were obtained on VG-AUTOSPEC
spectrometer. IR spectra were taken on a SHIMADZU 435
infrared spectrophotometer. Elemental analysis were performed
using a Vario-EL elemental analyzer.
(
Fig. 2) [19]. Most of the imidazole containing compounds dis-
play biological activities, probably due to their involvement in
catalytic processes at the active sites of enzymes due its pKa
6.1. Synthesis of 2,4-bis (benzyloxy)-6-(5H)-one-1,3,5-triazine (1)
[
34,35]. In this context, we introduced the imidazole group in
to the triazine moiety (6–11) but mono-, di- and tri-substituted
imidazoloaniline containing s-triazine derivatives (6–11) dis-
play moderate activity. Therefore imidazole group is not influ-
encing the antibacterial activity of s-triazine derivatives (6–11).
Introduction of methyl group in benzylamine and by changing
the substitution pattern from mono to di- and tri-substituted
chiral benzylamine containing s-triazine derivatives (12–14)
displayed moderate antibacterial activity and comparable with
the previously reported benzylamine containing s-triazine deri-
vatives. In overall, trisubstituted s-triazines are more active
than the mono and disubstituted s-triazines. All s-triazine deri-
vatives in this communication are inactive towards P. aerugi-
Benzyl alcohol (24, 2.16 g, 20 mmol) in 20 ml THF was
added drop-wise to an aqueous solution of 5% NaOH (10 ml)
at 0–5 °C. The temperature was allowed to increase 25 °C and
kept for reflux for 1 h. Cyanuric chloride (23, 1.83 g, 10 mmol)
in THF was added at 10 °C and after reflux for 10 h, removed
the solvent and extracted with ethyl acetate. Recrystallization
from ethanol afforded 1 as colorless solid (2.16 g., 70%). m.p.
1
152 °C; H NMR (CDCl
): δ 1.4 (b, 1H); 5.47 (s, 4H); 7.45
): δ 160, 134.3, 128.7, 128.6, 70.7;
MS (FAB): 310 (M + 1); IR (KBr): 3405, 3032, 2795, 1677,
3
1
3
(m, 10H); C NMR (CDCl
3
–
1
1639, 1491 cm ; Calc. for C17
H N O : C, 66.01; H, 4.89; N,
15 3 3
–
1
nosa at the maximum concentration of 250 μg ml . We
observed that all the 22 compounds did not display any anti-
fungal activity.
13.58%. Found: C, 65.97; H, 4.82; N, 13.55%.
6
.2. 2,4-Bis (4-methyl benzyloxy)-6-(5H)-one-1,3,5-triazine (2)
5
. Conclusion
Similar procedure as for 1 led to 2 (2.19 g., 65%). m.p.
1
1
38–140 °C; H NMR (CDCl ): δ 1.9 (b, 1H); 2.3 (s, 6H);
3
In conclusion, four series of substituted s-triazines were
5.35 (s, 4H); 7.1 (d, J = 8.9 Hz, 4H); 7.40 (d, J = 8.6 Hz,
synthesized and evaluated for antibacterial activity. Most of
the compounds exhibited moderate to significant in vitro anti-
bacterial activity. Among them, compounds 2, 6, 9, 10, 18 and
4H); MS (FAB): 338 (M + 1); IR (KBr): 3413, 3025, 2765,
–
1
1664, 1642, 1510 cm ; Calc. for C H N O : C, 67.64; H,
1
9 19 3 3
5.68; N, 12.46%. Found: C, 67.58; H, 5.61; N, 12.33%.

1244
K. Srinivas et al. / European Journal of Medicinal Chemistry 41 (2006) 1240–1246
6
.3. 2,4-Bis (4-methoxy benzyloxy)-6-(5H)-one-1,3,5-triazine (3)
using ethyl acetate/hexane (1:20 v/v) as eluent. (1.96 g, 95%).
1
m.p. 198 °C; H NMR (CDCl ): δ 3.6 (s, 3H); 7.2 (m, 4H);
3
7
.45 (m, 6H); 8.0 (d, J = 8 Hz, 2H); 8.35 (d, J = 8.2 Hz, 2H);
Similar procedure as for 1 led to 3 (2.28 g., 62%). m.p.
1
MS (FAB): 356 (M + 1); IR (KBr): 3064, 2924, 1592,
1
4
(
45 °C; H NMR (CDCl ): δ 1.2 (b, 1H); 3.8 (s, 6H); 5.0 (s,
3
–
1
1
1
507 cm ; Calc. for C H N O : C, 74.35; H, 4.82; N,
22 17 3 2
H); 6.85 (d, J = 8.5 Hz, 4H); 7.4 (d, J = 8.1 Hz, 4H); MS
1.82%; Found: C, 74.32; H, 4.80; N, 11.79%.
FAB): 370 (M + 1); IR (KBr): 3402, 3039, 2778, 1672, 1625,
–
1
1
502 cm ; Calc. for C H N O : C, 61.78; H, 5.18; N,
19 19 3 5
1
1.38%. Found: C, 61.71; H, 5.14; N, 11.33%.
6.8. 1-Ethyl-2-(4-nitro-phenyl)-4,5-diphenyl-1H-imidazole (33)
6
.4. 2,4-Bis (4-fluorobenzyloxy)-6-(5H)-one-1,3,5-triazine (4)
Above procedure was adopted except ethyl iodide was used
instead of methyl iodide to synthesize 33 (1.99 g, 93%). m.p.
1
1
(
92 °C; H NMR (CDCl ): δ 1.1 (t, 3H); 4.0 (q, 2H); 7.1–7.2
Similar procedure as for 1 led to 4 (2.35 g., 68%). m.p.
3
1
m, 4H); 7.4–7.6 (m, 6H); 7.95 (d, J = 7 Hz, 2H); 8.35 (d,
J = 7 Hz, 2H); MS (FAB): 370 (M + 1); IR (KBr): 3060,
972, 1592, 1508 cm ; Calc. for C H N O : C, 74.78; H,
23 19 3 2
.18; N, 11.37%. Found: C, 74.75; H, 5.16; N, 11.34%.
1
7
3
1
1
62–164 °C; H NMR (CDCl ): δ 2.3 (b, 1H); 5.55 (s, 4H);
3
.25 (d, J = 9.0 Hz, 4H); 7.6 (d, J = 9.2 Hz, 4H); MS (FAB):
–
1
2
5
46 (M + 1); IR (KBr): 3432, 3012, 2759, 1666, 1621,
–
1
507 cm ; Calc. for C H F N O : C, 59.13; H, 3.79; N,
1
7 13 2 3 3
2.17%. Found: C, 59.06; H, 3.65; N, 12.09%.
6.9. 4-(1-Methyl-4,5-diphenyl-1H-imidazol-2-yl)-phenylamine
(34)
6
.5. 2,4-Bis (4-chlorobenzyloxy)-6-(5H)-one-1,3,5-triazine (5)
Similar procedure as for 1 led to 5 (2.26 g., 60%). m.p.
Palladium–carbon catalyst (10%) was added portion-wise
1
1
7
(
1
68–169 °C; H NMR (CDCl ): δ 2.4 (b, 1H); 5.5 (s, 4H);
during 5–10 min to a hot solution of 32 (1 g, 2.8 mmol) in
ethanol (100 ml) containing hydrazine hydrate (0.7 g,
14 mmol). The mixture was heated under reflux for 1 h. The
hot solution was filtered through a Whatman paper to remove
Pd and further filtrate was filtered through silica gel (5 g) and
the solvent was evaporated. Pure product was obtained and
3
.35 (d, J = 7.9 Hz, 4H); 7.55 (d, J = 8.5 Hz, 4H); MS
FAB): 378 (M + 1); IR (KBr): 3413, 3033, 2787, 1663, 1630,
–
1
513 cm ; Calc. for C H Cl N O : C, 53.99; H, 3.46; N,
17 13 2 3 3
1
1.11%. Found: C, 53.88; H, 3.38; N, 11.02%.
used without further purification (0.9 g, 97%). m.p. 204 °C;
6
.6. 2-(4-Nitro-phenyl)-4,5-diphenyl-1H-imidazole (31)
A mixture of benzil 29 (2.1 g, 10 mmol), ammonium acetate
1
H NMR (CDCl ): δ 3.55 (s, 3H); 4.6 (b, 2H); 6.75 (d,
3
J = 8.1 Hz, 2H); 7.15–7.25 (m, 4H); 7.45–7.55 (m, 8H); MS
(
1
1
FAB): 326 (M + 1); IR (KBr): 3428, 3206, 2925, 1613,
470 cm ; Calc. for C H N : C, 81.20; H, 5.89; N,
22 19 3
2.91%. Found: C, 81.18; H, 5.87; N, 12.87%.
(
7.7 g, 0.1 mol) in glacial acetic acid (30 ml) was stirred at
–
1
8
0 °C for 1 h under nitrogen atmosphere. p-Nitro benzaldehyde
3
0 (1.51 g, 10 mmol) in glacial acetic acid (10 ml) was added
drop-wise over a period of 15 min at the same temperature and
stirred for another 4 h. The resulting homogeneous solution
was poured over crushed ice (200 g). The yellow precipitate
was collected by filtration and washed with cold water, then
dried under vacuum. The crude product was recrystallized
6
.10. 4-(1-Ethyl-4,5-diphenyl-1H-imidazol-2-yl)-phenylamine (35)
It is synthesized according to above procedure (0.94 g,
1
97%). m.p. 182 °C; H NMR (CDCl
): δ 1.1 (t, 3H); 3.95 (q,
3
from ethyl acetate thrice to afford the pure 31 (2.73 g, 80%).
2H); 6.7–6.75 (d, J = 6 Hz, 2H); 7.2–7.3 (m, 4H); 7.45–7.55
1
m.p. 210 °C; H NMR (CDCl ): δ 7.2 (m, 4H); 7.45 (m, 6H);
(m, 8H); MS (FAB): 340 (M + 1); IR (KBr): 3423, 3312, 3199,
3
–
1
8
.0 (d, J = 8 Hz, 2H); 8.2 (b, NH); 8.35 (d, J = 8.2 Hz, 2H);
2928, 1609, 1538 cm ; Calc. for C23
H N : C, 81.38; H, 6.24;
21 3
MS (FAB): 342 (M + 1); IR (KBr): 3391, 1596, 1514,
N, 12.38%. Found: C, 81.35; H, 6.22; N, 12.34%.
–
1
1
1
446 cm ; Calc. for C H N O : C, 73.89; H, 4.43; N,
21 15 3 2
2.31%. Found: C, 73.86; H, 4.41; N, 12.27%.
6.11. 4,6-Dichloro-[1,3,5]triazin-2-yl)-[4-(1-methyl-4,5-
diphenyl-1H-imidazol-2-yl)-phenyl]-amine (6)
6
.7. 1-Methyl-2-(4-nitro-phenyl)-4,5-diphenyl-1H-imidazole (32)
To a solution of 34 (0.65 g, 2 mmol) in THF (25 ml),
K CO (0.97 g, 7 mmol) was added to a solution of 31 (2 g,
K CO (0.28 g, 2 mmol) was added at 0 °C under nitrogen
2
3
2
3
5
1
.8 mmol) in DMF (25 ml) at 0 °C under nitrogen. After
5 min, methyl iodide (0.85 g, 6 mmol) wad added in one
and stirred for 30 min. Cyanuric chloride 23 (0.55 g,
3 mmol) in THF (10 ml) was added drop-wise over a period
of 15 min. After stirring for another 2 h, solvent was evapo-
rated and purified by column chromatography using ethyl acet-
portion at 0 °C and continued stirring for 2 h. Then the mixture
was stirred overnight at room temperature and poured over
crushed ice (150 g). Filtered the reaction mixture, washed
with ice cold water for several times to remove DMF and
dried in oven. Purified the product by column chromatography
ate/hexane (1:5 v/v) as a eluent to afford the product (0.8 g,
1
85%). m.p. 165 °C; H NMR (DMSO-d ): δ 3.5 (s, 3H); 7.1
6
(m, 2H); 7.4 (m, 4H); 7.8(m, 8H); 11.3 (b, 1H); MS (FAB):

K. Srinivas et al. / European Journal of Medicinal Chemistry 41 (2006) 1240–1246
1245
4
1
1
73 (M + 1); IR (KBr): 3421, 3225, 3054, 2926, 1606,
of 15 min and kept for reflux for 24 h. Then the solvent was
evaporated and purified by column chromatography using
–
1
556 cm ; Calc. for C H Cl N : C, 63.43; H, 3.83; N,
2
5
18
2 6
7.75%. Found: C, 63.4; H, 3.81; N, 17.72%.
methanol/ethyl acetate (1:20 v/v) as eluent to afford the pro-
1
duct (0.57 g, 55%). m.p. 251 °C; H NMR (DMSO-d ): δ 3.4
6
(
s, 9H); 7.1 (m, 6H); 7.5 (m, 12H); 7.9 (m, 24H); 11.2 (b, 3H);
6
.12. (4,6-Dichloro-[1,3,5]triazin-2-yl)-[4-(1-ethyl-4,5-
1
3
C NMR (CDCl + DMSO-d ): δ 163.5, 144.3, 142.8, 135.4,
diphenyl-1H-imidazol-2-yl)-phenyl]-amine (7)
3
6
1
1
31.4, 130.7, 130.3, 129.8, 129.4, 128.6, 128.3, 128.1, 127.4,
27, 126.8, 120.5, 41.1; MS (ESI): 1052 (M + 1); IR (KBr):
Above procedure was adopted except 35 is used instead of
–
1
1
3427, 3025, 1649, 1553 cm ; Calc. for C69
H, 5.18; N, 15.99%. Found: C, 78.8; H, 5.14; N, 15.96%.
H N12: C, 78.83;
54
3
4 to synthesize 7 (0.82 g, 65%). m.p. 158 °C; H NMR
(
DMSO-d ): δ 1.2 (t, 3H); 3.9 (q, 2H); 7.1 (m, 2H); 7.4 (m,
6
1
3
4
1
1
4
3
6
1
H); 7.8(m, 8H); 11.3 (b, 1H); C NMR (DMSO-d ): δ 156.0,
6
6
.16. N,N′,N″-Tris-[4-(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)-
54.0, 150.5, 144.5, 142.0, 132.0, 131.7, 131.5, 131.3, 131.0,
30.2, 130.0, 129.8, 129.0, 128.0, 127.0, 126.5, 121.0, 118.0,
1.5, 14.5; MS (ESI): 487 (M + 1); IR (KBr): 3435, 3228,
phenyl]-[1,3,5]triazine-2,4,6-triamine (11)
–
1
057, 2928, 1609, 1557 cm ; Calc. for C H Cl N : C,
Above procedure was adopted except 35 is used instead of
2
6
20
2 6
1
4.07; H, 4.14; N, 17.24%. Found: C, 64.05; H, 4.11; N,
7.22%.
34 to synthesize 11 (0.55 g, 50%). m.p. 238 °C; H NMR
(DMSO-d ): δ 1.2 (t, 9H); 3.85 (q, 6H); 7.15 (m, 6H); 7.4
6
1
3
(
m, 12H); 7.8 (m, 24H); 11.5 (b, 3H); C NMR (CDCl3
+ DMSO-d ): δ 164, 144.5, 142.9, 135.4, 131.4, 130.9,
130.3, 129.8, 129.4, 128.6, 128.3, 128.1, 127.4, 127, 126.8,
6
.13. 6-Chloro-N,N′-bis-[4-(1-methyl-4,5-diphenyl-1H-
6
imidazol-2-yl)-phenyl]-[1,3,5] triazine-2,4-diamine (8)
1
3
20, 40.1, 14.8; MS (FAB): 1093 (M + 1); IR (KBr): 3432,
–
1
052, 1642, 1555, 1527 cm ; Calc. for C H N : C, 79.10;
7
2 60 12
To a solution of 34 (0.65 g, 2 mmol) in THF (25 ml),
H, 5.53; N, 15.37%. Found: C, 79.08; H, 5.51; N, 15.33%.
Compounds 12–14 were synthesized according to the
reported procedure and characterization data for 12 and 14
can be found in literature [30,31].
K CO (0.28 g, 2 mmol) was added at 0 °C under nitrogen
2
3
and stirred for 30 min. Cyanuric chloride 23 (0.18 g,
mmol) in THF (10 ml) was added drop-wise over a period
of 15 min and stirred for overnight. Then the solvent was eva-
porated and purified by column chromatography using ethyl
1
acetate/hexane (2:3 v/v) as eluent to afford the product
6.17. 6-Chloro-bis [(R)-1-methyl benzylamino]-1,3,5-triazine
(13)
1
(
0.49 g, 55%). m.p. 212 °C; H NMR (DMSO-d ): δ 3.45 (s,
6
6
H); 7.15 (m, 4H); 7.4 (m, 8H); 7.85 (m, 16H); 11.1 (b, 2H);
MS (FAB): 762 (M + 1); IR (KBr): 3390, 3284, 3054, 2924,
This compound (13) was synthesized according to the
–
1
1
594, 1570 cm ; Calc. for C H ClN : C, 74.05; H, 4.76; N,
47 36 9
reported procedure (2.12 g., 10 mmol, 60%) [16b]. m.p.
1
6.54%. Found: C, 74.02; H, 4.74; N, 16.51%.
1
7
3 °C; H NMR (CDCl ): δ 1.3 (m, 6H); 2.3 (b, 2H); 4.95
3
(
m, 2H); 7.25 (m, 10H); MS (FAB): 354 (M + 1); IR (KBr):
–
1
6
2
.14. 6-Chloro-N,N′-bis-[4-(1-ethyl-4,5-diphenyl-1H-imidazol-
-yl)-phenyl]-[1,3,5] triazine-2,4-diamine (9)
3464 cm ; Calc. for C H ClN : C, 64.49; H, 5.70; N,
19 20 5
19.79%; Found: C, 64.38; H, 5.61; N, 19.70%.
Compounds 15–22 were synthesized according to the
reported procedure and characterization data can be found in
literature [32].
Above procedure was adopted except 35 is used instead of
4 to synthesize 9 (0.5 g, 50%). m.p. 223 °C; H NMR
1
3
(
(
DMSO-d ): δ 1.3 (t, 6H); 3.95 (q, 4H); 7.15 (m, 4H); 7.4
6
m, 8H); 7.9 (m, 16H); 11.5 (b, 2H); C NMR (DMSO-d6):
1
3
Acknowledgements
δ 154.3, 152.6, 143.9, 143.5, 140.9, 135.3, 130.9, 130.6, 130.4,
1
1
30.2, 129.9, 129.3, 129.0, 128.5, 127.6, 127.4, 126.4, 126.2,
20.0, 119.5, 117.0, 41.0, 14.0; MS (FAB): 790 (M + 1); IR
We thank Director IICT and Head of the Division for the
encouragement. K.S. and U.S. thank to CSIR-New Delhi and
University Grants Commission New Delhi for fellowship. We
thank the referees for the suggestions. IIC Communication
No: 060607
–
1
(
KBr): 3398, 3285, 3054, 2924, 1599, 1578 cm ; Calc. for
C H ClN : C, 74.46; H, 5.10; N, 15.95%. Found: C, 74.43;
H, 5.07; N, 15.92%.
4
9
40
9
6
.15. N,N′,N″-Tris-[4-(1-methyl-4,5-diphenyl-1H-imidazol-2-
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