Synthesis of tri-arm star shaped 1, 3, 5-triazines catalyzed by 1,5,7-Triazabicyclo[4.4.0] dec-5-ene (TBD)

Article abstract of DOI:10.4067/s0717-97072014000400009

Facile solution method for the synthesis of tri-arm star shaped 1,3,5-triazines was developed using 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) by reaction of cyanuric chloride with O-nucleophiles.

Full text of DOI:10.4067/s0717-97072014000400009

J. Chil. Chem. Soc., 59, Nº 4 (2014)
SYNTHESIS OF TRI-ARM STAR SHAPED 1, 3, 5-TRIAZINES CATALYZED BY 1,5,7-TRIAZABICYCLO[4.4.0]
DEC-5-ENE (TBD)
MARZIE KARIMI, ALI REZA KARIMI*
Department of Chemistry, Faculty of Science, Arak University, Arak 38156-8-8349, Iran.
ABSTRACT
Facile solution method for the synthesis of tri-arm star shaped 1,3,5-triazines was developed using 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) by reaction of
cyanuric chloride with O-nucleophiles.
Keywords: Cyanuric chloride; 1,3,5-Triazines; Nucleophilic reactions; TBD.
suspension solution was filtered and washed with cold water (3×20 mL) to give
the compounds 3a-3g as the only products.
INTRODUCTION
General procedure for preparation of 3a, 3d , 3f using DBU in
solution phase: Crushed ice/water (10 mL) was added to stirred solution of
2,4,6-trichloro-1,3,5-triazine (1 mmol) in acetone (10 mL). To the resulting fine
white slurry, compounds 2a, 2d , 2f (3.2 mmol) and 1,8-Diazabicyclo[5.4.0]
undec-7-ene (DBU) (3 equiv), dissolved in 5 mL acetone/water mixture (1:1)
were added dropwise with vigorous stirring. The reaction mixture was stirred
for 2 h at 0 ºC and then warmed to room temperature. After stirring for 2h
at room temperature the reaction mixture was refluxed for 18 h and then the
resulting suspension solution was filtered and washed with cold water (3×20
mL) to give the compounds 3a, 3d , 3f as the only products.
General procedure for preparation of 3a-g using NaOH in solid phase:
NaOH (3.2 mmol) and compounds 2a-2g (3.2 mmol) in 1 mL water was mixed
in a mortar. After the solvent evaporated, cyanuric chloride (1 mmol) was
added to the dry residue and the mixture was grounded in a mortar until a fine
powder was formed. After storage at 0 ºC for 2 h, the mixture warmed to room
temperature.After being placed for 2h at room temperature the reaction mixture
was heated on the oil bath at 100 °C for 18 h. The contents were cooled to room
temperature and mixed thoroughly with 10 mL of ethanol. The products were
filtered off and washed with cold water and ethanol.
2,4,6-Trisubstituted-1,3,5-triazine derivatives are very efficient and
important compounds having considerable properties like antifungal,1
antitumor,2 antibacterial3 and antiviral4 activities.
Diverse bases such as NaOH, K CO , NaH, DIPEA have been utilized for
synthesis of 2,4,6-trisubstituted-1,3,25-tri3azine. There are different conditions
such as use of various solvents like THF, acetone, mixture of acetone and water,
acetonitrile. Also some of reactions are performed under inert atmosphere
using Ar.5-8 Industrially, synthesis of these compounds are carried out in
homogeneous phase with KOH or NaOH as catalysts.9
Moreover, application of metal catalysts in the synthesis of bioactive
compounds is sometimes unwanted since the presence of even minute amount
of residual metal would lead to serious consequences. Loss of catalyst due to
the separation difficulties and corrosion problems in the equipments are other
disadvantages of these catalysts.
The known methods5-9 suffered from the drawbacks of low yield,
prolonged reaction time, separation difficulties, by-products and the use of
toxic solvents and catalysts. The above disadvantages make these methods a
little bit complicated to use. Consequently, there is a need for a convenient,
facile and efficient method and better yields.
1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) is a bicyclic guanidine base
that is known as super base. Among super bases, TBD has high pKa value (pKa
= 24.97) and has been widely utilized in organic synthesis.10 For example,
it can promote diverse organic reactions including Wittig reaction, Horner–
Wadsworth–Emmons reactions,11 secondary amine alkylation,12 carboxylation
of propylene glycol with CO2,13 synthesis of symmetrically N,N-substituted
ureas,14 5- and 6-enolexo aldolisation of acyclic ketoaldehydes,15 intramolecular
aldolization of acyclic ketoaldehydes16 and etc. Considering what was mentiond
above, we were interested to develop facile methods for the synthesis of tri-arm
star shaped 1,3,5-triazines by reaction of cyanuric chloride with some O- and
N-nucleophiles (Scheme 1).
RESULTS AND DISCUSSION
In liquid phase, the nucleophiles 2a-g and TBD as base were dissolved in
acetone/water and were added to a suspension solution of cyanuric chloride
in iced water/acetone. The reaction mixture was stirred for 2h at 0 ºC, 2h at
room temperature and 18 h at 60 °C. The resulting suspension solution was
filtered and washed with cold water to yield the compounds 3a-3g (Scheme 1
and Table 1).
An investigation of base quantity and the solvent effect on the reaction
indicated that the best yield was obtained using 30 mol% of TBD at acetone/
water solution. The reactions were completed in 22 h and after separation, gave
excellent isolated yields (Table 1). The amount of base could be reduced to 20
mol% (Table 1, entries 3a-3b) without affecting the yield.
EXPERIMENTAL
Materials
Table 1. Synthesis of tri-arm star shaped 1,3,5-triazines 3a-g in different
conditions.
All chemicals were purchased from Merck Chemical Co. (Germany),
Fluka Chemical Co. (Switzerland) and Acros Organics N.V./S.A. (Belgium).
Techniques
TBDa (Solution
phase)b
DBUa (Solution
phase)b
NaOH (Solid
phase)c
Mps were measured on an Electrothermal 9100 apparatus. 1H-NMR and
13C-NMR spectra were recorded on a Bruker 300 MHz instrument (Germany).
Fourier transform infrared (FTIR) spectra were recorded on Galaxy series
FTIR 5000 spectrophotometer (England). Spectra of solid were performed
by using KBr pellets. Vibration transition frequencies were reported in wave
numbers (cm-1).
Product
Yieldsd
Yieldsd
Yieldsd
3a
3b
3c
3d
3e
3f
85%a / 81%e
85%a / 80%e
78%a
41%
78%
76%
75%
85%
75%
82%
74%
-
-
38%
-
General procedure for preparation of 3a-g using TBD in solution
phase: Crushed ice/water (10 mL) was added to stirred solution of
2,4,6-trichloro-1,3,5-triazine (1 mmol) in acetone (10 mL). To the resulting fine
white slurry, compounds 2a-2g (3.2 mmol) and 1,5,7-triazabicyclo[4.4.0]dec-
5-ene (TBD) (30 mol%), dissolved in 5 mL acetone/water mixture (1:1) were
added dropwise with vigorous stirring. The reaction mixture was stirred for 2
h at 0 ºC and then warmed to room temperature. After stirring for 2h at room
temperature the reaction mixture was refluxed for 18 h and then the resulting
85%a
84%a
86%a
35%
-
3g
84%a
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e-mail: a-karimi@araku.ac.ir

J. Chil. Chem. Soc., 59, Nº 4 (2014)
aTBD: 30 mol%. Acetone/water (1:1); Reaction times at three different
Table 2. 1H-NMR, 13C-NMR, FTIR spectra data of 3a-g.
b
temperatures: 0 °C=2 h, r.t.=2 h, 60 °C=18 h. cReaction times at three different
temperatures: 0 °C=2h, r.t.=2h, 100 °C=18 h. dYields refer to isolated products.
eTBD: 20 mol%.
Product
Spectral data
1H-NMR (CDCl , δ ppm): 7.34 (d, 6H, J = 8.2 Hz, Harom)
,
7.93 (d, 6H, J = 8.32 Hz, H ), 10.00 (s, 3H, CHO). 13C-NMR
(CDCl3, δ ppm): 122.2,ar1om31.3, 134.3, 155.6, 173.2, 190.6.
FT-IR Peaks (cm-1): 3103, 3070, 2835, 1703, 1568, 1371,
1213, 808. Anal. Calcd for C24H N O6: C, 65.31; H, 3.43; N,
9.52. Found: C, 65.54; H, 3.76;1N5 , 39.88.
3a
1H-NMR (CDCl3, δ ppm): 7.41 (d, 3H, J = 8.1 and 1.1 Hz,
Harom), 7.57 (t, 3H, J = 7.8 Hz, Harom), 7.65 (s, 3H, J = 1.0
Hz, Harom), 7.77 (d, 3H, J = 7.2 and 1.0 Hz, Harom) 10 (s, 3H,
CHO). FT-IR Peaks (cm-1): 3080, 2823, 2735, 1701, 1570,
1377, 1228, 842. Anal. Calcd for C H N3O6: C, 65.31; H,
3.43; N, 9.52. Found: C, 65.62; H, 32.4701;5N, 9.76.
3b
3c
1H-NMR (DMSO- d6, δ ppm): 3.94 (s, 9H, OCH3), 7.98
(d, 3H, J = 1.5 Hz, Harom), 8.24 (d, 3H, J = 1.5 Hz, Harom),
10.00 (s, 3H, CHO). 13C-NMR (DMSO- d6, δ ppm): 57.8,
117.3, 118.5, 134.9, 137.4, 142.6, 153.4, 169.3, 191.1. FT-
IR Peaks (cm-1): 3084, 2835, 1707, 1537, 1465, 1357, 1292.
Anal. Calcd for C27H N6O15: C, 48.66; H, 2.72; N, 12.61.
Found: C, 48.96; H, 21.98 2; N, 12.96.
1H-NMR (CDCl3, δ ppm): 7.36 (d, 6H, J = 7.6 Hz, Harom)
,
8.32 (d, 6H, J = 7.6 Hz, H ). FT-IR Peaks (cm-1): 3117,
3082, 1616, 1601, 1568, 14a8ro7m, 1373, 1348, 1207, 858. Anal.
Calcd for C21H12N O : C, 51.23; H, 2.46; N, 17.07. Found:
C, 51.46; H, 2.72; 6N,917.36.
3d
3e
3f
Scheme 1. Synthesis of tri-arm star shaped 1,3,5-triazines.
Next we examined the solid phase synthesis of 3a-3g by using NaOH as
base. In this method, NaOH and compounds 2a-2g in 1 mL water were mixed
in a mortar. After the solvent evaporated, cyanuric chloride was added to the
dry residue and the mixture was ground in a mortar until a fine powder was
formed. The mixture was placed for 2h at 0 ºC, 2h at room temperature and 18
h at 100 °C. Contents were cooled to room temperature and mixed thoroughly
with 10 mL of ethanol. The product was filtered off and washed with cold water
and ethanol.
The solution phase of above reaction using DBU at acetone/water was also
investigated (Table 1). We compared the results obtained from TBD with DBU
as another organobase. As it is shown in Table 1, TBD is an effective base for
this reaction and the yield of reaction using TBD is higher than DBU.
In these methods the products did not need any additional purification. The
reaction was performed in a simple way and the precipitates were separated
from the reaction medium easily. The solvent-free condition by using NaOH
was simple and did not need to use of solvent, but the yield of the products was
a little bit. TBD and DBU did not respond to this method.
1H-NMR (DMSO- d , δ ppm): 7.46 (d, 6H, J = 8.4 Hz,
Harom), 7.93 (d, 6H, J6= 8.4 Hz, Harom). FT-IR Peaks (cm-
1): 3103, 3047, 2235, 1608, 1570, 1500, 1369, 1215. Anal.
Calcd for C24H12N O : C, 66.67; H, 2.80; N, 19.44. Found:
C, 66.95; H, 3.10; 6N,319.76.
1H-NMR (CDCl , δ ppm): 2.61 (s, 3H, CH3), 7.23 (d, 6H,
J = 8.6 Hz, Harom3), 7.99 (d, 6H, J = 8.6 Hz, Harom). FT-IR
Peaks (cm-1): 3070, 2920, 1687, 1568, 1502, 1379, 1265,
850. Anal. Calcd for C H N O6: C, 67.07; H, 4.38; N, 8.69.
Found: C, 67.35; H, 4.2570;21N,38.96.
1H-NMR (DMSO- d6, δ ppm): 6.67 (3H, s, CHmethine) 7.35-
7.83 (m, 12H, Harom). 13C-NMR (DMSO- d6, δ ppm): 91.4,
116.2, 116.8, 123.6, 124.3, 133.1, 150.3, 153.9, 162.4,
166.1. FT-IR Peaks (cm-1): 3080, 3061, 1736, 1645, 1554,
1340, 845. Anal. Calcd for C30H N3O9: C, 64.18; H, 2.69;
N, 7.48. Found: C, 64.65; H, 2.821;5N, 7.78.
3g
Thus due to these results and disadvantage of metal catalysts application in
the synthesis of bioactive compounds, it can be deduced that using TBD in the
synthesis of these compounds is better than NaOH.
Chemical structure and purity of 3a–g were proved by using FTIR,
1H-NMR and 13C-NMR spectroscopic techniques. These data are shown in
Table 2.
As an example, the FTIR data for compound 3c showed absorption around
2835 cm-1, which was assigned to the C–H stretching vibration of CHO groups.
The peak appearing at 1707 cm-1 confirmed the presence of aldehyde groups in
this compound (Fig. 1). The 1H-NMR spectrum of compound 3c showed peak
at 3.94 ppm as a singlet, which was assigned for CH group. The peaks at 7.98
and 8.24 ppm were assigned to aromatic protons. Al3so a singlet peak in 10.00
ppm was assigned to CHO group (Fig. 1). The 13C NMR spectrum also shows
9 signals for the product 3c.
Fig. 1. FT-IR and 1H-NMR spectrum (DMSO- d6) of compound 3c.
CONCLUSIONS
In conclusion, we have reported a simple, high yielding and convenient
protocol for the synthesis of tri-arm star shaped 1,3,5-triazines in solution and
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J. Chil. Chem. Soc., 59, Nº 4 (2014)
solid phase. This reaction is easy to perform and the purification protocol is
simple. No side products were observed for this reaction.
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ACKNOWLEDGMENT
We gratefully acknowledge the financial support from the Research
Council of Arak University.
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