Synthesis of 6-( 2-Furyl ) and 6-( 2-Thienyl )-4-trifluoromethylpyrimidinones and pyrimidines from 4-( 2-Heteroaryl )-4-methoxy-1 , 1 , 1-trifluoro-3-buten-2-ones

Neste trabalho é apresentada a síntese, em rendimentos razoáveis (50-67%), de novos sistemas biheterocíclicos, duas 6-(2-heteroaril)-4-trifluormetil-2-(1H)-pirimidinonas (2a,b) e uma série de dez 6-(2-heteroaril)-4-trifluormetilpirimidinas (3a,b 7a,b) a partir da ciclocondensação de 1,1,1-trifluor-4-(2-heteroaril)-4-metoxi-3-buten-2-onas com uréia e amidinas. As estruturas de todos os compostos foram atribuídas pelos dados de análise elementar, espectrometria de massas e dados de RMN 1H e 13C. Os dados de RMN 1H e 13C são mostrados de maneira sistemática. Também apresentamos os dados de difração de raios-X de um monocristal da 2-amino-6-(tien-2-il)-4-trifluormetilpirimidina (5b).


Introduction
Interest in perfluoroalkylated heterocyclic compounds is largely due to the fact that they have enhanced biological activity and can be used as medicinal or agricultural chemicals. 1-8][11][12][13][14][15] Perfluoroalkylated N-containing heterocycles can be obtained by various methods, including the widely used reactions of 1,3-dicarbonyl compounds with binucleophiles.0][21][22][23] The patent reports show only melting point as accessible analytical data for these compounds.
In the search for the optimum cyclocondensations condition for 1a, 1b and amidines acetamidine hydrochloride was used as a model amidine.The cyclocondensations in MeOH or iPrOH under Brönsted HCl or Lewis BF 3 •OEt 2 catalysis were unsuccessful, the reactants were recovered.In contrast to the synthesis of 4-polyfluoroalkylpyrimidines by condensation in refluxing iPrOH under Lewis BF 3 •OEt 2 catalysis for 4 to 26 h, 12 we have obtained products 6-(2heteroaryl)-2-methyl-4-trifluoromethyl-pyrimidines 3a and 3b in good yields using alkaline medium, reacting acetamidine hydrochloride with a 1 mol L -1 KOH aqueous solution and adding to MeOH solution of 1a or 1b at room temperature.TLC analyses during reaction period have revealed that the 1,3-dielectrophiles were consumed after 1 hour, furnishing good yields of the pyrimidines 3.
thiomethyl-4-trifluoromethyl-pyrimidines 7a, 7b were obtained in similar alkaline medium with the procedure described above.The structure of all compounds was determined from 1 H, 13 C and mass spectrometry.Based on our previous reports on the chemistry of 6-aryl-4trifluoromethyl-1H-pyrimidin-2-ones and 6-aryl-4trifluoromethyl-pyrimidines derived from 4-aryl-4-methoxy-1,1,1-trifluoro-3-buten-2-ones, the assignment of each signal in the 13 C NMR spectra of compounds 2-7 was accurately established. 15,16heme 1. [3 + 3] The 1 H and 13 C spectra of products showed set of signals attributed to aromatic pyrimidines 3a, 3b to 7a, 7b.The structure of compound 2-amino-6-(2-thienyl)-4trifluoromethyl-pyrimidine 5b was established by X-ray diffraction analysis.The overall view of the molecule is shown in Figure 1.The 6-(2-thienyl)-pyrimidine system is virtually coplanar (the mean deviation of the atoms from the plane is 0.008 Å).The thienyl ring suffers a rotational disorder, atoms S1 and C7 were modeled as exchanged with a minor occupancy fraction refined to 19.6%.The trifluoromethyl group presents a rotational disorder; the three F atoms were refined in a position rotated approximately 45º from their original positions at 5.3% occupancy.Crystal data for 5b are shown in Table 1.

Experimental
The synthesis of 4-(2-heteroaryl)-4-methoxy-1,1,1trifluoro-3-buten-2-one, 1 has been reported elsewhere. 20rea, amidines and BF 3 •OEt 2 were used as obtained from commercial suppliers.MeOH and i-PrOH were purified before using. 1 mol L -1 solution of NaOH was prepared by the dissolution of 0.40 g of NaOH in 100 mL of distilled water.Yields listed in Table 2 are of isolated compounds.All melting points were determined on a Reichert Thermovar apparatus and are uncorrected.The 1 H and 13 C spectra were recorded at 298 K on a Bruker DPX 400 spectrometer ( 1 H at 400.13 MHz, 13 C at 100.63 MHz) with digital resolution of ± 0.01 ppm.All the chemical shifts are expressed in ppm, 1 H and 13 C are reported with respect to internal TMS.0.1 mol L -1 CDCl 3 solutions were used except with compounds 2, 0.1 mol L -1 in DMSO-d 6 .H-H and C-F coupling constants are in Hz.Mass spectra were registered in a HP 5973 MSD connected to a HP 6890 GC and interfaced by a Pentium PC.The GC was equipped with a split-splitless injector, auto-sampler, cross-linked HP-5 capillary column (30 m, 0.32 mm of internal diameter), and helium was used as the carrier.Elemental analyses were performed on a Perkin-Elmer 2400 CHN elemental analyzer (São Paulo University-São Paulo, Brazil).The crystal and molecular structure of 5b was determined by a single crystal X-ray diffraction study.Data were recorded on a Bruker Kappa Apex II CCD area detector with graphite monochromatized Mo Ka radiation (l 0.71073 Å).The data were processed with SAINT and SADABS.The  structure was solved by direct methods (SHELXS-97) 26 and additional atoms were located in the difference Fourier map and refined on F 2 using the SHELXTL and Wingx packages. 27

Figure 1 .
Figure 1.ORTEP Diagram of the X-ray crystal structure of 5b at a probability level of 50%.