Artigo Amino Ester Triazina

7/28/2019 Artigo Amino Ester Triazina

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Microwave-Assisted Synthesis and Dynamic Behaviour ofN

2,N4,N6-Tris(1H-pyrazolyl)-1,3,5-triazine-2,4,6-triamines

Angel Daz-Ortiz,a Jose Elguero,b Antonio de la Hoz,a* Agustn Jimenez,a Andres Moreno,a Sergio Morenoa andAna Sanchez-Migallona

a Departamento de Qumica Inorganica, Organica y Bioqumica, Facultad de Ciencias Qumicas, Universidad de Castilla-La Mancha,E-13071 Ciudad Real, Spain, Fax: 34926295411, Tel: 34926295318, E-mail: [email protected]

b Instituto de Qumica Medica (C.S.I.C.), Juan de la Cierva, 3, E-28006 Madrid, Spain, Fax: 34915644853, Tel: 34914110874,E-mail: [email protected]

Dedicated to Juan Carlos del Amo, in memoriam (Madrid, 11.3.2004)

Keywords: DNMR, Microwave, Pyrazolyltriazines, Solvent-free

Received: June 29, 2004; Accepted: February 7, 2005

AbstractA series of N2,N4,N6-tris(1H-pyrazolyl)-1,3,5-triazine-2,4,6-triamines has been synthesised

under microwave irradiation in solvent-free conditions. By reaction of pyrazolylamineswith cyanuric chloride and 2-chloro-4,6-diamino-1,3,5-triazines under microwaveirradiation, 1,3,5-triazine-2,4,6-triamies with symmetrical and asymmetrical substitution,respectively, can be obtained. In the latter case, the procedure can be easily adapted byaddition of a small amount of Dimethyl Sulfoxide (DMSO) for the preparation of poly-mer-supported triazines, with application in supramolecular combinatorial synthesis. Atlow temperature, the presence of two or four conformers has been detected for symmet-rically and asymmetrically substituted derivatives respectively. 1D- and 2D-exchange spec-troscopy studies in various solvents and at different temperatures have been used todetermine the equilibrium constants and the activation free energies of the restrictedrotation about the amino triazine bond. A plot of the activation free energy versustemperature shows a good linear correlation and confirms that the same process ispresent in all of the compounds under investigation.

1 Introduction

Controlling structures using supramolecular interactions isan area of great interest in chemistry and biochemistry aswell as in crystal engineering [1, 2]. Aminotriazines havebeen used in the formation of supramolecular structuresusing hydrogen bonds [3 6]. The importance of these sec-ondary interactions has also been thoroughly studied [7].For instance, the interaction between cyanuric acid andmelamine [8] is well documented and the stability of the

resulting complexes has been used to obtain polymers inthe solid state. Modification of the system formed by cya-nuric acid and/or melamine has allowed the synthesis oflinear polymers [9, 10], the non-covalent synthesis of nano-structures with the assembly of up to 27 components with144 hydrogen bonds [11 14], the chemoselective synthesisof dendrimers based on melamine [15], the construction ofmolecular tectonics from pentaerythritol derivatives [16],the preparation of electrooptic thin films by anchoring amelamine template to a cleaned glass or Si(100) substrate[17], the preparation of photoresponsive melamine barbi-turate assemblies [18], as well as diastereoselective and

enantioselective non-covalent synthesis of melamine bar-biturate assemblies [19].

Tagged triazine libraries have also been used in forwardchemical genetics as a powerful tool for novel drug candi-dates [20 21]. Since the advent of combinatorial chemis-try, several triazine-based libraries have been preparedboth in solid phase and in solution [22]. An 8000-memberlibrary of trisamino and amino-oxy-1,3,5-triazines was pre-pared recently using a microwave-assisted nucleophilicsubstitution procedure with cellulose-membrane-bound

monochlorotriazines [23].Microwave-assisted organic synthesis is a high-speedmethodology with clear benefits: significant rate enhance-ments and higher product yields are usually observed [24 28]. In several cases, the stereo- and/or regiochemical out-come of microwave-assisted reactions has been found tobe different to that observed under classical heating [29,30]. The combination of microwave-heating methodologyand combinatorial chemistry provides an increase in speedand effectiveness in the synthesis of organic compounds,advantages that cannot be achieved by conventional heat-ing methods. Thus, in recent years, a considerable number

QSAR Comb. Sci. 2005, 24 DOI: 10.1002/qsar.200420116 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 649

Full Papers


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of publications have described the preparation of diverselibraries using a combination of microwave and combina-torial chemistry methodologies [31 33].

We planned the synthesis of several melamine deriva-tives modified by attachment to azoles, in order to changethe nature of the intermolecular bonds and to allow inter-

actions with other substrates. With the same purpose the

synthesis of cyanuric acid derivatives is under develop-ment. It is well known that reaction of amines with cyanu-ric chloride leads to the corresponding substitution prod-ucts. In this regard the substitution of two chloride atomsand consequently preparation of diaminotriazines occursunder mild conditions, at room temperature in the pres-

ence of a base. Following this strategy we have recently de-

650 2005 WILEY-VCH Verlag GmbH & C o. KGaA, Weinheim QSAR Comb. Sci. 2005, 24

Scheme 1. Structure of compounds 1 8.

Full Papers Angel Daz-Ortiz et al.


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scribed the preparation of 2-chloro-4,6-bis-pyrazolylami-notriazines [34].

In this paper we describe the synthesis both of N2,N4,N6-tris((1H-pyrazol-1-yl)phenyl)-1,3,5-triazine-2,4,6-triamines1 3 and N2,N4,N6-tris(1-phenyl-1H-pyrazolyl)-1,3,5-tria-zine-2,4,6-triamines 4 5 by reaction of cyanuric chloride

with the corresponding amines, and of asymmetrically sub-stituted N2-(2-(1H-pyrazol-1-yl)phenyl)-N4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-1,3,5-triazine-2,4,6-triamine 6 andN2-(3-(1H-pyrazol-1-yl)phenyl)-N4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-1,3,5-triazine-2,4,6-triamine 7 by reaction ofthe corresponding amines with N4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-2-chloro-1,3,5-triazine-4,6-diamine 8 (Scheme 1).

2 Discussion

2.1 Synthesis of1 7

Melamine derivatives have been usually prepared from cy-anuric chloride by sequential substitution with amines[35]; or by substitution of sulfones. [22] Recently a solvent-free procedure [36] and a microwave-assisted synthesis indioxane Dimethylformamide (DMF) and basic condi-

tions has been described [37]. Although the first and sec-ond substitution can be performed at low temperature inthe presence of a base, the third substitution usually re-quires high temperatures and long reaction times.

Derivatives 1 5 with symmetrical substitution patternswere prepared by reaction of cyanuric chloride with the

corresponding amine using microwave irradiation in sol-vent-free conditions in only 10 min with moderate to highyields (42 62%) (Scheme 2). Six equivalents of theamine were required in order to neutralise the hydrogenchloride produced in the reaction. Similarly, derivatives6 7 with asymmetrical substitution patterns were pre-pared in excellent yield by reaction of N4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-2-chloro-1,3,5-triazine-4,6-diamine8 with two equivalents of the corresponding amine. Reac-tions were performed in a focused microwave reactorwith full control of the incident power and reaction tem-perature.

It is remarkable that no reaction occurs by conventional

heating under comparable reaction conditions (tempera-ture and time). In order to obtain similar yields by conven-tional heating, reactions should be performed in Tetrahy-drofuran (THF) at reflux for five days in the presence ofdiisopropylethylamine (DIPEA) as base. However, even

QSAR Comb. Sci. 2005, 24 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 651

Scheme 2. Reaction conditions and yield for the preparation of compounds 1 7.

Scheme 3. Reaction conditions and yield for the preparation of compound 8.

Microwave-Assisted Synthesis and Dynamic Behaviour of N2,N4,N6-Tris(1H-pyrazolyl)-1,3,5-triazine-2,4,6-triamines


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Figure 1. NMR spectra of compound 2 in DMF-d7 solution: a) 223 K and b) 363 K.



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time was performed in order to obtain the pure diagonalpeaks without exchange cross-peaks. Experiments wereperformed at the temperature of the slow process in

DMF-d7 and CDCl3. Rate constants can be deduced fromthe spectra according to the following equation:


Table1. 1H-NMR spectra of compounds 1 7, rapid process, d [ppm], J [Hz] (see Scheme 1 for atom numbering).

Compound 1 1 1 2 3 4 5 5 6 7

Solvent DMF-d7 CDCl3 DMSO-d6 DMF-d7 DMF-d7 CDCl3 DMSO-d6 DMF-d7 DMF-d7 DMF-d7Temp. [ K] 293 293 293 363 363 393 393 393 363 363H-3 pyrazole d

J7.92(d)

1.4

7.86(d)

1.5

7.87(d)

1.2

7.69(d)

1.4

7.69(d)

1.7

7.90(s)

7.96 (s) 7.70(s)

7.69(bs)

H-4 pyrazole dJ

6.58 (dd)2.1, 1.4

6.48 (dd)2.2, 1.5

6.52(dd)2.7, 1.2

6.48(d)1.4

6.50(dd)2.5, 1.7

6.23(bs)

6.50(t)2.1

6.50(bs)

H-5 pyrazole dJ

8.30(d)2.1

7.75(d)2.2

7.83(d)2.7

8.25(d)1.3

8.32(d)2.5

78.5(bs)

8.56(s)

8.68(s)

8.34(s)

8.30(bs)

H-2 dJ

8.26(s)

8.00( AAXX)8.7, 5.1,0.3

78.5(bs)

7.76(d)7.8

7.83(d)7.9

7.91(AAXX)9.0

7.97( AAXX)8.8, 5.2,0.3

H-3 dJ

7.60(dd)1.3, 8.1

7.57.2(m)

7.38(dd)1.5, 8.0

7.79( AAXX)8.7, 5.1,0.3

78.5(bs)

7.44(t)7.8

7.49(t)7.8

7.79(AAXX)9.0

7.75( AAXX)8.8, 5.2,0.3

H-4 dJ

7.25(td)7.8

7.13(t)8.1

7.28(td)1.3, 8.1

7.49(d)7.9

7 8.5(bs)

7.26(t)7.4

7.30(t)6.9

H-5 dJ

7.44(td)8.8

7.57.2(m)

7.44(td)1.7, 9.1

7.34(dd)7.9, 8.3

7.79( AAXX)8.7, 5.1,0.3

78.5(bs)

7.44(t)7.8

7.49(t)7.8

7.79(AAXX)9.0

7.75( AAXX)8.8, 5.2,0.3

H-6 dJ

8.40(d)9.0

8.49(d)8.1

8.36(dd)1.5, 8.3

7.85(d)8.2

8.00( AAXX)8.7, 5.1,0.3

78.5(bs)

7.44(t)7.8

7.83(d)7.9

7.91(AAXX)9.0

7.97( AAXX)8.8, 5.2,0.3

NH d 9.84(s)

9.46(s)

10.94(s)

9.35(s)

9.60(s)

9.12(bs)

8.96(s)

9.02(s)

9.71(s)

9.56(s)

H-3 pyrazole d 7.90

(s)

7.69

(bs)H-4 pyrazole dJ

6.57(t)2.1

6.48(bs)

H-5 pyrazole d 8.30(s)

8.30(bs)

H-2 d 8.0(s)

H-3 dJ

7.60(dd)8.2, 1.4

H-4 dJ

7.28(t)7.5

7.53(t)8.1

H-5 d

J

7.45

(td)7.7, 1.6

7.43

(t)8.3

H-6 dJ

8.47(d)8.1

7.80(d)8.3

NH d 9.82(s)

9.59(s)



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Table2. 1H-NMR spectra of compounds 1 5, slow process, d [ppm], J [Hz] (see Scheme 1).

Table 2a

Compound 1 1 2 3 5

Solvent DMF-d7 CDCl3 DMF-d7 DMF-d7 DMF-d7Temp. [ K] 213 203 223 223 223H-3 pyrazole d [a] 7.85 (s) 8.45 (s) 7.87 (s) 7.91 (s)H-4 pyrazole d 6.65 (s) 6.49 (s) 6.63 (s) 6.66 (s) H-5 pyrazole d

J8.00 (s) 7.74 (s) 8.69 (s) 8.73 (d)

2.09.07 (s)

H-2 dJ

7.87 (s) 7.92 (d)9.0

7.89 (d)7.5

H-3 d

J

7.63 (m) 7.5 7.1 (m) 8.17 (d)

9.0

7.60 (t)

7.8H-4 d

J7.28 (m) 7.5 7.1 (m) 8.04 (d)

8.2 7.36 (d)

7.4H-5 d

J7.47 (m) 7.5 7.1 (m) 7.48 (t)

8.18.17 (d)9.0

7.60 (t)7.8

H-6 dJ

nda 8.39 (d)8.0

7.61 (d)8.2

7.92 (d)9.0

7.89 (d)7.5

NH d 10.14 (s) 9.70 (s) 10.45 (s) 10.40 (s) 10.33 (s)

Table 2b

Compound 1 1 2 3 5

Solvent DMF-d7 CDCl3 DMF-d7 DMF-d7 DMF-d7T ( K ) 213 203 223 223 223H-3 pyrazole d

d

8.31 (s) 7.91 (s) 8.30 (s)8.29 (s)

7.87 (s) 7.91 (s)

H-4 pyrazole dd

6.69 (s) 6.49 (s) 6.66 (s)6.62 (s)

6.66 (s)

H-5 pyrazole dJ

d

8.02 (s) 7.74 (s) 8.63 (s)8.61 (s)

8.73 (d)2.0

9.07 (s)

H-2

dJ

d

7.87 (s)7.85 (s)

7.8 8.2 (m) 7.89 (d)7.5

H-3 dJ

7.63 (m) 7.5 7.1 (m) 7.8 8.2 (m) 7.60 (t)7.8

H-4 dJ

d

J

7.28 (m) 7.5 7.1 (m) 7.98 (d)8.37.93 (d)8.6

7.45 (d)7.87.31 (d)7.5

H-5 dJ

d

J

7.47 (m) 7.5 7.1 (m) 7.23 (t)8.27.19 (t)8.1

7.8 8.2 (m) 7.60 (t)7.8



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R lnA/tmX (lnL)X1/tm (1)

where AijIij/Mj, tm is the mixing time. Iij(tm)/Mj and Xare the square matrix of eigenvectors of Ai such that

X1AXLdiag (li), with li the ith eigenvalue of A. Iij

can be deduced by measuring the volume of each peak in-tensity directly from the spectrum. Mj is the volume of thediagonal peak of the spectrum registered with a mixingtime close to 0 and without any chemical exchange.

Activation free energies for compounds 1 3, 5 were cal-culated (Table 4) from the rate constants according toSandstrm [42].

The calculated activation free energies correspond to49 79 kJ mol1 and they were determined in a wide rangeof temperatures (203 298 K); the representation ofDG

versus temperature showed a linear plot with a good corre-lation constant, R20.99 (Figure 2). This linear plot per-mitted the calculation of DH4.40 kJ mol1 and DS0.27 kJ mol1 K1. The DG value was similar to thosemeasured for N-arylguanidines and related aminotriazines[38, 39, 43].

3 Conclusions

N2,N4,N6-Tris(1H-pyrazolyl)-1,3,5-triazine-2,4,6-triamineswith symmetrical and asymmetrical subtitution patternwere prepared in good yield under microwave irradiationunder solvent-free conditions in 10 min. Comparison withclassical heating shows that higher yields and shorter reac-tion times are observed under microwave irradiation. Withsterically hindered derivatives such as 1, 6 and 7, no reac-


Table 2. (cont.)

Table 2b

Compound 1 1 2 3 5

H-6 dJ

d

J

8.48 (m)8.42 (m)

8.47 (d)7.58.46 (d)8.0

7.61 (d)8.37.58 (d)8.3

7.8 8.2 (m) 7.89 (d)7.5

NH dd

d

10.03 (s)9.96 (s)

9.64 (s)9.59 (s)

10.49 (s)10.45 (s)10.20 (s)

10.48 (s)10.21 (s)10.17 (s)

10.19 (s)10.07 (s)9.88 (s)

a Not detected.

Table3. Ratio of conformers determined by 1H-NMR spectros-copy

Compound Solvent Temperature[ K]

Conformera

Conformerb

1 DMF-d7 213 40.7 59.31 CDCl3 203 46.4 53.42 DMF-d7 223 57.3 42.73 DMF-d7 223 62.8 37.25 DMF-d7 298 57.1 42.95 DMF-d7 223 67.2 32.8

Table4. Activation free energies determined from 1D and 2D EXSY spectra

Com-pound

Solvent Temperature[ K]

DG [kJ mol1]

NMRexperiment

Processa>b

Processb>b

Mean value

1 CDCl3 203 2D EXSY 49.07 51.96 50.032 DMF-d7 223 1D EXSY 54.24 57.13 55.683 DMF-d7 223 1D EXSY 55.84 57.42 56.635 DMF-d7 223 1D EXSY 57.98 57.59 57.795 DMF-d7 298 2D EXSY 74.35 79.08 76.715 DMF-d7 298 1D EXSY 76.85 76.33 76.59



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tion occurs by conventional heating. The procedure wasadapted for the preparation of polymer-supported tria-zines with applications in combinatorial chemistry in

supramolecular polymer-supported synthesis.The structures were determined in solution using NMR

spectroscopy. Conformers resulting from the restricted ro-tation about the amino triazine bond were detected andidentified in solution and at low temperatures. The re-stricted rotation was studied by 1D and 2D EXSY. A plotof the calculated activation free energies versus tempera-ture showed a good correlation coefficient, indicating thata unique and similar process occurred in all the present tri-azines.

The present study shows the interest of microwave irra-diation and solvent-free conditions in organic synthesisand especially for preparing sterically hindered com-

pounds. Also the importance of determining the molecularstructure in solution in order to gain an insight into possi-ble supramolecular interactions was shown.

4. Experimental Section

4.1 Apparatus

Microwave-assisted reactions were performed in a mono-mode microwave reactor PROLABO MAXIDIGESTMX350, modified with a mechanical stirrer and an infrared

pyrometer. Incident power and temperature were control-led by computer using the software MPX-2 from PACAMElectronica. Melting points were determined using a SMP-3 melting-point apparatus and are uncorrected. The IRspectra were obtained with an FT-IR Nicolet-550 spectro-photometer. The mass spectra (electrospray ionisationmode, ESI ) were recorded on a HPLC-MSD flow-injec-tion analysis apparatus. Flash column chromatography wasperformed on silica gel 60 (Merck, 230 400 mesh).

NMR spectra were recorded on a VARIAN INNOVA500 spectrometer operating at 499.791 MHz for protonspecroscopy. Spectra were recorded at the temperature in-

dicated (0.1 K) with a probe calibrated with methanol.The standard VARIAN pulse sequence was used (VNMR6.1B software). Samples were prepared by dissolving thetriazine (0.25 mmol) in DMF-d7, DMSO-d6 and CDCl3(0.6 mL) under argon atmosphere.

The 2D exchange spectra (EXSY) were acquired in the

phase-sensitive mode using the States Haberkorn meth-od [44]. Typically, a 3.1 kHz spectral width, 16 transients of2048 data points were collected for each 400 t1 increments.A 1-s relaxation delay, an 11-s (908) pulse width and a0.165-s acquisition time were used. The free induction de-cays were processed with square cosine-bell filters in bothdimensions and zero filling was applied prior to doubleFourier transition.

The 1D exchange spectra (EXSY) were acquired usingthe standard 1D NOESY pulse sequence with 512 transi-ents, a 0.8-s relaxation delay and a 1.892-s acquisition time.

Determination of the kinetic parameters required twoexperiments with mixing times of 1 s (optimised) for the

exchange experiment and 0.02 s for the non-exchangespectra, respectively. The cross peak/diagonal ratio was de-termined by integrating the volume under the peaks.

4.2 Synthesis of N2,N4,N6-Tris(1H-pyrazolyl)-1,3,5-

triazine-2,4,6-triamines 1 5

4.2.1 General Procedure

A mixture of cyanuric chloride (2 mmol, 0.373 g) and theappropriate amine (12 mmol, 1.906 g) was introduced in aPyrex flask and irradiated at 90 W (185 8C) for 10 min. Af-ter cooling, the crude mixture was extracted with the ap-

propriate solvent and the corresponding triazines were pu-rified as described below.

4.2.2 N2,N4,N6-Tris(2-(1H-pyrazol-1-yl)phenyl)-1,3,5-tria-

zine-2,4,6-triamine (1)

From 1-(2-aminophenyl)pyrazole, temperature 1858C:The crude was extracted with dichloromethane (325 mL) and filtered, the filtrate was purified by columnchromatography using hexane/ethyl acetate (8:2) gradient(1: 1). Yield 0.633 g (57 %), mp 190 1918C. IR (KBr) nmax3386, 1597, 1450, 1416 cm1. 13C-NMR (DMSO-d6, 293 K)

163.85 (C-2, C-4, C-6), 141.69 (C-3 pyrazole), 132.60 (C-1), 130.14 (C-2), 129.92 (C-5 pyrazole), 127.80 (C-5),125.55 (C-4), 123.84 (C-6), 122.60 (C-3), 107.52 (C-4 pyr-azole). MS (EI) m/z 553.2 (M).



From 1-(3-aminophenyl)pyrazole, temperature 1858C:The crude was extracted with hot water (225 mL) andthe solid was filtered and purified by column chromatogra-phy using hexane/ethyl acetate (8 : 2) gradient (1: 1). Yield


Figure 2. Linear plot of the calculated activation free energy(mean value) versus temperature for compounds 1 3, 5 as indi-cated in Table 4.



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0.685 g (62 %). mp 120 1228C. IR (KBr) nmax 3280, 1586,1413 cm1. 13C-NMR (DMSO-d6, 393 K) 164.75, 141.47,140.59, 130.08, 128.37, 119.03, 113.08, 111.40, 108.40. 13C-NMR (DMF-d7, 363 K) 165.58, 141.91, 141.27, 141.14,129.87, 127.93, 119.00, 113.43, 111.65, 107.84. MS (ESI )m/z 553.2 (MH).



From 1-(4-aminophenyl)pyrazole, temperature 1858C:The crude was extracted with hot water (225 mL) andthe solid was filtered and purified by column chromatogra-phy using hexane/ethyl acetate (1:1) gradient ethyl ace-tate. Yield 0.555 g (50%), mp >298 8C. IR (KBr) nmax3284, 1618, 1587 cm1. 13C-NMR (DMF-d7, 298 K) 165.21,141.10, 139.45, 135.57, 127.82, 121.35, 119.46, 107.97. MS(ESI ) m/z 553.2 (MH).

4.2.5 N2,N4,N6-Tris(1-phenyl-1H-pyrazol-3-yl)-1,3,5-tria-


From 3-amino-1-phenylpyrazole, temperature 1858C: Thecrude was extracted with water (425 mL) and the solidwas filtered and washed with diethyl ether (25 mL). Yield0.565 g (51%), mp 160 8C decomposes. IR (KBr) nmax 3415,1599, 1502 cm1. MS (ESI ) m/z 553.2 (MH).

4.2.6 N2,N4,N6-Tris(1-phenyl-1H-pyrazol-4-yl)-1,3,5-tria-


From 4-amino-1-phenylpyrazole, temperature 1858C: The

crude was extracted with water (425 mL) and the solidwas filtered and washed with 0.01 m HCl (225 mL). Thecrude product was purified by column chromatography us-ing hexane/ethyl acetate (7: 3) gradient (1: 1). Yield0.469 g (42 %), mp 259 2618C. IR (KBr) nmax 3214, 1599,1395 cm1. 13C-NMR (DMSO-d6, 393 K) 163.71, 139.55,133.80, 128.60, 124.97, 124.24, 117.55, 117.46. MS (ESI )

m/z 553.2 (MH).

4.3 Synthesis of Triazines 6 and 7

4.3.1 General Procedure

A mixture ofN4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-2-chlo-ro-1,3,5-triazine-4,6-diamine (8) (1 mmol, 0.43 g) and theappropriate amine (2 mmol, 0.32 g) was introduced into aPyrex flask and irradiated at 90 W for 10 min. After cool-ing, the crude mixture was extracted with a solution of0.01 m HCl (250 mL), the solid was filtered and washedwith water (5 mL) and ethyl ether (5 mL) to afford thepure product.

4.3.2 N2-(2-(1H-Pyrazol-1-yl)phenyl)-N4,N6-bis(4-(1H-

pyrazol-1-yl)phenyl)-1,3,5-triazine-2,4,6-triamine (6)

Temperature 1408C. Yield 0.370 g (67 %), mp 200 2018C.IR (KBr) nmax 3394, 1622, 1597, 1525 cm

1. 13C-NMR(DMF-d7, 363 K) 164.01, 141.43, 140.89, 138.47, 136.25,

132.70, 131.57, 127.97, 127.65, 124.31, 122.03, 119.54,107.64, 107.46. MS (ESI ) m/z 553.2 (MH).

4.3.3 N2-(3-(1H-Pyrazol-1-yl)phenyl)-N4,N6-bis(4-(1H-

pyrazol-1-yl)phenyl)-1,3,5-triazine-2,4,6-triamine (7)

Temperature 1258C. Yield 0.508 g (92%), mp 122 1238C.IR (KBr) nmax 3392, 1584, 1416 cm

1. 13C-NMR (DMF-d7,363 K) 164.65, 141.58, 141.27, 141.14, 140.84, 138.79,136.06, 129.84, 127.95, 127.58, 121.97, 119.53, 119.08,113.69, 111.90, 107.82, 107.61. MS (ESI ) m/z 553.2 (M

H) (dimer).

4.4 Polymer-Supported Triazine (9)

A mixture of poly(styrene-co-divinylbenzene) aminome-thylated 200 400 mesh, 4 mmol N/g (2 mmol, 0.500 g),N4,N6-bis(4-(1H-pyrazol-1-yl)phenyl)-2-chloro-1,3,5-tria-zine-4,6-diamine (8) (1 mmol, 0.429 g) and DMSO (1 mL)were introduced into a Pyrex flask and irradiated at 90 Wand for 10 min, temperature 1308C. After cooling, thecrude mixture was washed with water (215 mL) the solidwas filtered and washed with ethanol (5 mL), then the sol-id was washed with ethyl acetate (215 mL) to afford0.856 g of resin. Loading of the resin (0.97 mmol/g of res-in). IR (KBr) n

max1583, 1527, 1496, 1408.

Acknowledgements

Financial support from the DGICYT of Spain throughproject CTQ2004-01177 and from the Consejera de Cien-cia y Tecnologa JCCM through project PAI-02-019 isgratefully acknowledged. NMR spectra were recorded atthe Regional Institute of Applied Scientific Research.

References

[1] J. M. Lehn, Proc. Nat. Acad. Sci. 2002, 99, 49774982, andreferences therein.

[2] a) A. D. Burrows, C. W. Chan, M. M. Chowdhry, J. E.McGrady, D. M. P. Mingos, Chem. Soc. Rev. 1995, 329 339.b) M. D. Hollingsworth, Science 2002, 295, 2410 2413. c) B.Moulton, M. J. Zaworotko, Chem. Rev. 2001, 101, 16291658. d) G. R. Desiraju, Chem. Commun. 1997, 14751482.e) G. R. Desiraju, Acc. Chem. Res. 2002, 35, 565 573.f) G. R. Desiraju, Nature 2001, 412, 397 400.

[3] a) E. A. Archer, H. Gong, M. J. Krische, Tetrahedron 2001,57, 1139 1159. b) M. Acedo, E. De Clercq, R. Eritja, J.Org. Chem. 1995, 60, 6262 6269. c) U. Von Krosigk, S. A.




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