A solvent-free synthesis of beta-enamino trihalomethyl ketones

Abstracts

An efficient green procedure to prepare a series of twenty-six 4-amino-1,1,1-trihalo-3-alken-2-ones [CX3C(O)CH=C(R¹)NR² R³, where X = F, Cl, R¹ = H, Me, and R²/R³ = H/Ph, H/4-F-Ph, H/Bn, H/(CH2)2OH, Me/Ph, Me/Bu, Et/Et, -(CH2)4-] from the solvent-free reaction of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with primary and secondary amines at room temperature for five minutes is reported (yields of 73-99%).

solvent-free; enaminones; enones; trihalomethyl-compounds; green chemistry

Este trabalho apresenta uma metodologia, ambientalmente adequada e mais econômica em relação àquelas descritas na literatura, para a obtenção de uma série de vinte e seis 4-amino-1,1,1-trialo-3-alquen-2-onas [CX3C(O)CH=C(R¹)NR² R³, com X = F, Cl, R¹ = H, Me, e R²/R³ = H/Ph, H/4-F-Ph, H/Bn, H/(CH2)2OH, Me/Ph, Me/Bu, Et/Et, -(CH2)4-], a partir da reação de 1,1,1-trialo-4-alcóxi-3-alquen-2-onas com aminas primárias e secundárias, na ausência de solvente, a temperatura ambiente e em cinco minutos (rendimentos de 73-99%).

ARTICLE

A solvent-free synthesis of b-enamino trihalomethyl ketones

Marcos A. P. Martins^*; Rodrigo L. Peres; Gabriela F. Fiss; Frantiescoli A. Dimer; Rodrigo Mayer; Clarissa P. Frizzo; Mara R. B. Marzari, Nilo Zanatta; Helio G. Bonacorso

Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria-RS, Brazil

ABSTRACT

An efficient green procedure to prepare a series of twenty-six 4-amino-1,1,1-trihalo-3-alken-2-ones [CX₃C(O)CH=C(R¹)NR² R³, where X = F, Cl, R¹ = H, Me, and R²/R³ = H/Ph, H/4-F-Ph, H/Bn, H/(CH₂)₂OH, Me/Ph, Me/Bu, Et/Et, -(CH₂)₄-] from the solvent-free reaction of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with primary and secondary amines at room temperature for five minutes is reported (yields of 73-99%).

Keywords: solvent-free, enaminones, enones, trihalomethyl-compounds, green chemistry

RESUMO

Este trabalho apresenta uma metodologia, ambientalmente adequada e mais econômica em relação àquelas descritas na literatura, para a obtenção de uma série de vinte e seis 4-amino-1,1,1-trialo-3-alquen-2-onas [CX₃C(O)CH=C(R¹)NR² R³, com X = F, Cl, R¹ = H, Me, e R²/R³ = H/Ph, H/4-F-Ph, H/Bn, H/(CH₂)₂OH, Me/Ph, Me/Bu, Et/Et, -(CH₂)₄-], a partir da reação de 1,1,1-trialo-4-alcóxi-3-alquen-2-onas com aminas primárias e secundárias, na ausência de solvente, a temperatura ambiente e em cinco minutos (rendimentos de 73-99%).

Introduction

b-Enaminones and b-enamino esters are useful synthetic buildings blocks for various pharmaceuticals^1,2 and bioactive heterocycles.³ They have been used for the preparation of different important antibacterial,⁴ anticonvulsant,⁵ anti-inflammatory⁵ and antitumour agents.⁶ They are also the intermediates for the synthesis of several aminoacids,^7-9 aminols,⁸ peptides and alkaloids.¹⁰ It is well-known that the introduction of trihalomethyl groups into heterocyclic compounds may have a significant influence on their biological and physical properties. The most convenient method to construct trihalomethylated compounds is to use halogen-containing building blocks as starting reagents.^11,12 Therefore, the development of synthetic methods for trihalogenated synthetic building blocks has been an important field in organic synthesis. b-enamino trihalomethyl ketones are commonly prepared from b-alkoxy vinyl trihalomethyl ketones¹² or acetylenes.¹³ One of the most effective methods used to synthesize b-enamino trihalomethyl ketones is the amination reaction of b-alkoxyvinyl trifluoro[chloro]methyl ketones.¹⁴ Vdovenko et al.¹⁵ have obtained four trihalomethylated enaminones and one non-halogenated enaminone by a similar route. Recently, we reported the synthesis of trihalomethyl substituted enaminones and trihalomethylated isoxazolines obtained from by the ultrasound promoted reaction of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with aniline in aqueous media.¹⁶ We also published the preparation of trihalomethyl substituted b-ethoxy-b-enamino ketones from the reaction of 1,1,1-trihalo-4,4-dietoxy-3-alken-2-ones with amines in solvent-free conditions and the utility of this intermediates to obtainment of N-azolyl amines.¹⁷ Another general method for the synthesis of trihalomethylated enaminones is from trifluoromethylated enones using trifluoropropynyl lithium with N-methoxy-N-methylbenzamide (Weinreb benzamide).¹⁸ Unfortunately, in general, the processes to synthesize trihalomethyl substituted b-enamino ketones suffers from limitations, such as long reaction times, multi-step reactions and tedious work-up.^19,20 Thus, because of the applicability of b-enamino trihalomethyl ketones as a promising building blocks for the synthesis heterocycles,^21,22 a simple, general and high yielding one-pot approach for the synthesis of this enaminones is highly desirable. In particular, it has been shown that syntheses which are carried out in solvent-free conditions are often rapid, regio- or chemoselective, occur in high yields and have environmental and economic advantages. Considering our interest to explore new and green routes in organic synthesis, we decided to investigate the synthesis of b-enamino trihalomethyl ketones by the solvent-free reaction of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with primary and secondary amines.

Results and Discussion

The starting material, 1,1,1-trihalo-4-alkoxy-3-alken-2-ones, 1, was synthesized from the reaction of the respective enol ether and trifluoroacetic anhydride or trichloroacetyl chloride.¹² The amines were purchased commercially.

To establish the potential of the synthesis of b-enamino trihalomethyl ketones in solvent-free conditions, we began our investigation by reaction of 1,1,1-trifluoro-4-alcoxy-3-buten-2-one 1a with aniline without solvent. In order to evaluate if this conditions was better than others solvents, we performed the same reaction by screening a variety of different solvents. The effect of the solvent on the reaction of enones 1 and amines 2 under some solvents was summarized in Table 1.

Taking into account that this reaction is considered a nucleophilic addition/substitution, we carried out the reaction in polar solvents. When ethanol was used as solvent at room temperature, the yield of enaminones obtained was 20%. However, when the reaction was performed at 0 ºC in ethanol, and it was stirring for 5 min, we obtained the yield of 3a increased to 49%. At the same temperature, but a reaction time of 10 min, the yield of 3a was increased to 66%. When the reaction was carried out in acetonitrile at 0 ºC and, after stirring for 15 min, the yield of 3a remained similar that obtained in ethanol. Finally, when the reaction was carried out under solvent-free conditions, a significant improve on the yield was observed (yield > 90%, Table 1). Several enone:amine molar ratios were tested, and the best ratio we found was 1:1. Thus, the typical experiment was established by the addition of the appropriate amine 2 to 1,1,1-trihalo-4-alkoxy-3-alken-2-one 1 at 0 ºC, and the mixture was stirred at room temperature for 5 minutes (Scheme 1). After the reaction time, the desired products were obtained in the pure form and side products were not observed. The results summarized in Table 2 show that primary and secondary amines, both aromatic and aliphatic, with linear and branched N-substituents reacted without any significant difference to give the corresponding b-enamino trifluoro[chloro]methyl ketones in good yields. In the preparation of some compounds (3a, 3o and 3v), where the less reactive amine was used, the reaction was performed in water as solvent and under ultrasound irradiation for 15-20 min (entries 1, 15, and 22, Table 2). The isolated products were characterized by their melting points, ¹H and ¹³C NMR, GC/MS spectral analysis.

In comparison with a procedure used by Hojo and coworkers,^12,14 the method shown here by us presented the advantages of decrease of reaction time, absence of solvent and easy work-up. As regards to previous works published by us, for example, using ultrasound irradiation, this procedure is even faster and to execute this procedure do not it necessary the ultrasound equipment, and the synthesis can be proceed in large scale. Recently, some solvent-free condensation reaction has been described in the literature,²³ and the results provide that this process is suitable due their simplicity, excellent yields and easy purification of products. In many of these studies, enaminones are the intermediate formed. Thus, based in previous works,¹⁵ the following sequence of steps appears to afford a satisfactory explanation for the mode of formation of the products (Scheme 2). This reaction involves the initial attack of the amine nitrogen atom on the enone b-carbon with a charge delocalization to the carbonyl group and a subsequent elimination of the alcohol molecule.

In each case, the stereochemistry of the 4-amino-1,1,1-trihalo-3-alken-2-ones 3 was assigned based on the ¹H NMR spectroscopy. The downfield peak of the amino protons (10-12 ppm) in compounds 3a-d and 3o-r suggests the existence of an intramolecular hydrogen bond and, therefore, a cis-relationship between the NH and C=O groups, for which reason a Z-configuration was deduced. The formation of the Z-isomer in compounds 3h-j and 3v-x was proven by the coupling constants of the hydrogen atoms attached on the double bond (J_H3-H4 = 7.1-7.9 Hz) and also by a distinct splitting of the H4 atom on the amino group NH (12.9-13.5 Hz) fixed via an intramolecular hydrogen bond.⁷ The E-configuration of the b-enamino trihalomethyl ketones 3k-n and 3y-3z was confirmed by the J_H3-H4 coupling constants (12.4-12.8 Hz) of these compounds. The Z- and E-configurations proposed were confirmed by X-ray diffraction for compound 3q and 3u (Figure 1).²⁴

Conclusions

We reported the reactions of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with primary and secondary amines under solvent-free conditions. A range of 4-amino-1,1,1-trihalo-4-alkoxy-3-alken-2-ones were obtained in good to excellent yields. The reactions of 1,1,1-trihalo-4-alkoxy-3-alken-2-ones with amines were also studied and the stereochemistry of the products were dependent on the amines used. Moreover, to shorten the reaction time in relation to conventional methods, this procedure does not use organic solvents, which minimizes environmental impact and costs, and increases operational safety.

Experimental

General

Unless otherwise indicated, all common reagents and solvents were used as obtained from commercial suppliers without further purification. ¹H and ¹³C NMR spectra were recorded on a Bruker DPX 400 spectrometer (¹H at 400.13 MHz and ¹³C at 100.62 MHz) at 298 K with a digital resolution of ± 0.01 ppm, with 0.5 mol L^-1 solutions in CDCl₃ as solvent, containing TMS as internal standard. All spectra were acquired in a 5 mm tube, at natural abundance. J values are given in Hz. Mass spectra were registered in a HP 5973 MSD connected to a HP 6890 GC and interfaced by a Pentium PC. The CG 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 gas.

General procedure for the synthesis of the 4-amino-1,1,1-trihalo-3-alken-2-ones (3a-z)

The appropriate amine 2 (2 mmol) was added to enone 1 (2 mmol) at 0 ºC. The mixture equivalent was stirred at room temperature for 5 minutes. The product obtained, after undergoing reduced pressure for 1 hour, was pure enough for most purposes as indicated by physical and spectroscopic data. The solid products were recrystallized from hexane as solvent. Physical and spectroscopic data for compounds 3, see literature cited in the Table 2. The compounds 3b,e,f,g,l,p ,r,t,u,w,x,y ,z are not reported in the literature and physical and spectroscopic data are described below.

(Z)-1,1,1-Trifluoro-4-(4-fluorophenylamino)pent-3-en-2 -one (3b)

mw 247.19; mp 68-70 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 2.11 (3 H, s, Me), 5.54 (1H, s, CH), 7.15-7.43 (4 H, m, Ph) and 11.45 (1H, s, NH); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 20.1(CH₃), 90.9 (CH), 116.3, 116.6 (q, ¹J_CF 288), 127.3 (CH), 133.0(CH), 161.6 (d, ¹J_CF 248), 168.2 (C) and 176.8 (q, ²J_CF 33); m/z (EI) 247 (M⁺, 49%), 178 (100), 95 (34) and 75 (24). Anal. Calc. for C₁₁H₉NOF₄: C, 53.45; H, 3.67; N, 5.67. Found: C, 53.20; H, 3.65; N, 5.64.

(E)-1,1,1-Trifluoro-4-(methylphenylamino)pent-3-en-2 -one (3e)

mw 243.23; Oil; d_H (400 MHz; CDCl₃; Me₄Si) 2.39 (3H, s, Me), 3.35 (3H, s, NMe), 5.41 (1H, s, CH) and 6.63-7.46 (5H, m, Ph); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 19.1(CH₃), 41.6 (CH₃), 89.6 (CH), 117.8 (q, ¹J_CF 293), 126.4 (CH), 128.4 (CH), 129.1 (CH), 129.9 (CH), 168.0 (C) and 176.0 (q, ²J_CF 31); m/z (EI) 243 (M⁺, 45%), 147 (100), 146 (48), 131 (64), 77 (82) and 56 (97). Anal. Calc. for C₁₂H₁₂NOF₃: C, 59.26; H, 4.97; N, 5.76. Found: C, 58.81; H, 4.94; N, 5.72.

(E)-4-(Butylmethylamino)1,1,1-trifluoropent-3-en-2-one (3f)

mw 223.24; Oil; d_H (400 MHz; CDCl₃; Me₄Si) 0.96 (3H, t, Me), 1.36 (2H, m, CH₂), 1.57 (2H, m, CH₂), 2.60 (3H, s, Me), 3.04 (3H, s, NMe), 3.42 (2H, t, NCH₂) and 5.19 (1H, s, CH); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 13.4 (CH₃), 16.4 (CH₃), 19.6 (CH₃), 30.1(CH₂), 38.8 (CH₂), 52.0 (CH₂), 86.6 (CH), 117.9 (q, ¹J_CF 293), 167.5 (C) and 174.7 (q, ²J_CF 31); m/z (EI) 223 (M⁺, 33%), 180 (46), 154 (85), 112 (74) and 56 (100). Anal. Calc. for C₁₀H₁₆NOF₃: C, 53.80; H, 7.22; N, 6.27. Found: C, 53.42; H, 7.19; N, 6.23.

(E)-1,1,1-Trifluoro-4-(pyrrolidin-1-yl)pent-3-en-2-one (3g)

mw 207.19; mp 69-71 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 2.00 (4H, m, 2 × CH₂), 2.60 (3H, s, Me), 3.40 (2H, t, NCH₂), 3.50 (2H, t, NCH₂) and 5.10 (1H, s, CH); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 18.5 (CH₃), 24.6 (CH₂) , 24.9(CH₂), 48.8(CH₂), 49.1(CH₂), 87.3(CH), 118.1 (q, ¹J_CF 292), 166.0(C) and 174.7 (q, ²J_CF 30); m/z (EI) 207 (M⁺, 35%), 138 (100), 110 (17) and 70 (30). Anal. Calc. for C₉H₁₂NOF₃: C, 52.17; H, 5.84; N, 6.76. Found: C, 51.85; H, 5.80; N, 6.72.

(E)-4-(Butylmethylamino)-1,1,1-trifluorobut-3-en-2-one (3l)

mw 209.21; Oil; d_H (400 MHz; CDCl₃; Me₄Si) 0.95 (3H, t, Me), 1.33 (2H, m, CH₂), 1.61 (2H, m, CH₂), 2.94 (3H, s, NMe), 3.37 (2H, t, NCH₂), 5.59 (1H, d, CH) and 7.83 (1H, d, J 6.8); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 13.4 (CH₃), 19.4 (CH₃), 30.3 (CH₂), 35.6 (CH₂), 50.4 (CH₂), 86.9 (CH), 117.7 (q, ¹J_CF 291), 156.3 (CH) and 176.9 (q, ²J_CF 33); m/z (EI) 209 (M⁺, 40%), 166 (73), 140 (100) and 98 (70). Anal. Calc. for C₉H₁₄NOF₃: C, 51.67; H, 6.75; N, 6.70. Found: C, 51.34; H, 6.70; N, 6.65.

(Z)-1,1,1-Trichloro-4-(4-fluorophenylamino)pent-3-en-2 -one (3p)

mw 296.55; mp 68-70 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 2.10 (3H, s, Me), 5.89 (1H, s, CH), 7.08-7.18 (4H, m, Ph) and 11.05 (1H, s, NH); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 20.5 (CH₃), 88.4 (CH), 96.9 (CCl₃), 116.3 (CH), 116.5 (CH), 127.2 (CH), 133.4 (CH), 161.4 (d, ¹J_CF 248), 167.2 (C), 181.2 (C=O); m/z (EI) 295 (M⁺, 4%), 232 (18), 178 (100) and 95 (28). Anal. Calc. for C₁₁H₉NOFCl₃: C, 44.55; H, 3.06; N, 4.72. Found: C, 44.18; H, 3.03; N, 4.68.

(Z)-1,1,1-Trichloro-4-(2-hydroxyethylamino)pent-3-en-2 -one (3r)

mw 246.51; mp 80-82 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 2.14 (3H, s, Me), 3.53 (2H, q, NCH₂), 3.84 (2H, t, J 5.2, OCH₂), 5.71 (1H, s, CH) and 10.85 (1 H, s, NH); d_C (100 MHz; CDCl₃; Me₄Si) 19.9(CH₂) , 45.8(CH₂), 60.6(CH₂), 86.8 (CH) , 97.1 (CCl3), 169.7 (C) and 179.9; m/z (EI) 245 (M⁺, 3%), 182 (26), 128 (100), 82 (31) and 54 (16). Anal. Calc. for C₇H₁₀NO₂Cl₃ : C, 34.11; H, 4.09; N, 5.68. Found: C, 33.76; H, 4.05; N, 5.60.

(E)-4-(Butylmethylamino)-1,1,1-trichloropent-3-en-2-one (3t)

mw 272.60; Oil; d_H (400 MHz; CDCl₃; Me₄Si) 0.97 (3H, t, Me), 1.37 (2H, m, CH₂), 1.61 (2H, m, CH₂), 2.58 (3H, s, Me), 3.07 (3H, s, NMe), 3.39 (2 H, t, NCH₂) and 5.65 (1H, s, CH); d_C (100 MHz; CDCl₃; Me₄Si) 13.7 (CH₃), 19.9 (CH₃), 27.8 (CH₃), 32.8 (CH₂), 38.9 (CH₂), 49.2 (CH₂), 84.7(CH), 99.8 (CCl₃), 167.5 (C) and 178.8 (C=O); m/z 271 (EI) (M⁺, 26%), 236 (26), 208 (100), 154 (99) and 56 (96). Anal. Calc. for C₁₀H₁₆NOCl₃: C, 44.06; H, 5.92; N, 5.14. Found: C, 43.74; H, 5.87; N, 5.09.

(E)-1,1,1-Trichloro-4-(pyrrolidin-1-yl)pent-3-en-2-one (3u)

mw 256.56; mp 88-90 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 2.03 (4H, m, 2 × CH₂), 2.58 (3H, s, Me), 3.41 (2H, t, NCH₂), 3.56 (2H, t, NCH₂) and 5.57 (1H, s, CH); d_C (100 MHz; CDCl₃; Me₄Si) 18.2 (CH₂), 24.7 (CH₂), 25.1 (CH₂), 48.9 (CH₂), 49.0 (CH₂), 85.1 (CH), 99.7 (CCl₃), 165.8 (C) and 178.6; m/z (EI) 255 (M⁺, 2%), 192 (15), 138 (100) and 55 (16). Anal. Calc. for C₉H₁₂NOCl₃: C, 42.14; H, 4.71; N, 5.46. Found: C, 41.74; H, 4.67; N, 5.41.

(Z)-1,1,1-Trichloro-4-(4-fluorophenylamino)but-3-en-2 -one (3w)

mw 282.53; mp 70-71 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 5.96 (1H, d, CH), 7.07-7.09 (4H, m, Ph), 7.57 (1H, dd, J 7.8 and 13.0 Hz, CH) and 11.32 (1 H, s, NH); d_C (J_CF, Hz) (100 MHz; CDCl₃; Me₄Si) 88.2 (CH), 96.3 (CCl₃), 116.6 (CH), 116.9 (CH), 118.7 (CH), 135.4 (CH), 149.4 (CH), 160.1 (d, ¹J_CF 245) and 182.9 (C=O); m/z (EI) 281 (M⁺, 12%), 218 (24), 164 (100) and 95 (32). Anal. Calc. for C₁₀H₇NOFCl₃: C, 42.51; H, 2.50; N, 4.96. Found: C, 42.13; H, 2.47; N, 4.91.

(Z)-4-Benzylamino-1,1,1-trichlorobut-3-en-2-one (3x)

mw 278.56; Oil; d_H (400 MHz; CDCl₃; Me₄Si) 4.49 (2 H, d, CH₂), 5.72 (1 H, d, CH), 7.18 (1 H, dd, J 7.5 and 13.5 Hz, CH), 7.20-7.40 (5 H, m, Ph) and 9.93 (1H, s, NH); d_C (100 MHz; CDCl₃; Me₄Si) 85.2 (CH₂), 96.7 (CCl₃), 127.3 (CH), 128.2 (CH), 128.9 (CH), 136.2 (CH), 157.2 (CH) and 182.2 (C=O); m/z (EI) 277 (M⁺, 10%), 214 (19), 160 (100) and 77 (53). Anal. Calc. for C₁₁H₁₀NOCl₃: C, 47.43; H, 3.62; N, 5.03. Found: C, 47.06; H, 3.59; N, 4.92.

(E)-4-(butylmethylamino)-1,1,1-trichlorobut-3-en-2-one (3y)

mw 258.57; mp 82-84 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 0.96 (3H, t, Me), 1.36 (2H, m, CH₂), 1.62 (2H, m, CH₂), 2.95 (3H, s, NMe), 3.36 (2H, t, NCH₂), 5.59 (1H, d, CH) and 7.83 (1H, d, CH); d_C (100 MHz; CDCl₃; Me₄Si) 13.5 (CH₃), 19.5 (CH₃), 30.5 (CH₂), 35.7 (CH₂), 58.5 (CH₂), 84.8 (CH), 98.1(CCl₃), 156.9 (CH) and 180.7 (C=O); m/z (EI) 257 (M⁺, 4%), 194 (15), 140 (100) and 84 (22). Anal. Calc. for C₉H₁₄NOCl₃: C, 41.81; H, 5.46; N, 5.42. Found: C, 41.46; H, 5.37; N, 5.35.

(E)-1,1,1-Trichloro-4-diethylaminobut-3-en-2-one (3z)

mw 244.55; mp 78-80 ºC (from hexane); d_H (400 MHz; CDCl₃; Me₄Si) 1.24 (3 H, t, Me), 1.28 (3H, t, Me), 3.34 (2H, q, CH2), 3.40 (2H, q, CH2), 5.65 (1H, d, J 12.4 Hz, CH) and 7.80 (1H, d, J 12.4 Hz, CH); d_C (100 MHz; CDCl₃; Me₄Si) 11.5(CH₃), 14.6 (CH₃), 43.2 (CH₂), 51.0 (CH₂), 84.7(CH), 98.2 (CCl₃) and 155.5 (CH); m/z 243 (EI) (M⁺, 4%), 178 (12), 124 (100) and 82 (13). Anal. Calc. for C₈H₁₂NOCl₃: C, 39.29; H, 4.95; N, 5.73. Found: C, 39.00; H, 4.88; N, 5.65.

Acknowledgments

The autors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/PADCT), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) for financial support. The fellowships from CNPq, CAPES and FAPERGS are also acknowledged.

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11. Martins, M. A. P.; Cunico, W.; Pereira, C. M. P; Flores, A. F. C.; Bonacorso, H. G.; Zanatta, N.; Curr. Org. Synth. 2004, 1, 391 and references therein; Bonacorso, H. G.; Bittencourt, S. R. T.; Lourega, R. V. ; Flores, A. F. C. ; Zanatta, N; Martins, M. A. P. Synthesis 2000, 10, 1431; Martins, M. A. P; Flores, A. F. C.; Bastos, G. P.; Zanatta, N.; Bonacorso, H. G.; J. Heterocycl. Chem. 1999, 36, 837. Y Y

12. Hojo, M.; Masuda R.; Okada, E.; Synthesis 1986, 12, 1013; Gerus, I. I.; Gorbunova, M. G.; Vdovenko, S. I.; J. Org. Chem. USSR (Engl. Transl.) 1990, 26, 1623. Y

13. Linderman, R. J.; Kirollos, K. S.; Tetrahedron Lett. 1990, 31, 2689.

14. Hojo, M.; Masuda, R.; Okada, E.; Narumiya, H.; Marimoto, K.; Tetrahedron Lett. 1989, 30, 6173; Zanatta, N.; Flores, D. C.; Amaral, S. S.; Bonacorso, H. G.; Martins, M. A. P.; Flores, A. F. C.; Synlett 2005, 20, 3079. Y

15. Vdovenko, S. I.; Gerus, I. I.; Wójcik, J.; J. Phys. Org. Chem. 2001, 14, 533.

16. Martins, M. A. P. ; Pereira, C. M. P. ; Cunico, W.; Moura, S.; Rosa, F. A.; Peres, R. L.; Machado, P.; Zanatta N.; Bonacorso, H. G.; Ultrason. Sonochem. 2006, 13, 364.

17. Martins, M. A. P.; Cunico, W.; Brondani, S.; Peres, R. L.; Zimmermann, N.; Rosa, F. A.; Fiss, G. F.; Zanatta, N.; Bonacorso, H. G.; Synthesis 2006, 9, 1485.

18. Nahm, S.; Weinreb, S. M.; Tetrahedron Lett. 1981, 22, 3815.

19. Epifano, F.; Genovese, S.; Curini, M.; Tetrahedron Lett. 2007, 48, 2717; Lin, J.; Zhang L.-F.; Monatsh. Chem. 2007, 138, 77. Y

20. Zhang, Z. H.; Hu, J. Y.; J. Braz. Chem. Soc. 2006, 17, 1447.

21. Bonacorso, H. G.; Oliveira, M. R.; Costa, M. B.; da Silva, L. B.; Zanatta, N; Martins, M. A. P.; Flores, A. F. C.; J. Braz. Chem. Soc. 2005, 16, 868.

22. Zanatta, N.; Squizani, A. M. C.; Fantinel, L.; Nachtigall, F. M.; Borchhardt, D. M.; Bonacorso, H. G.; Martins, M. A. P.; J. Braz. Chem. Soc. 2005, 16, 1255.

23. Quiroga, J.; Insuasty, B.; Abonía, R.; Nogueras, M.; Sánchez, A.; Portilla, J.; Cobo, J.; Tetrahedron Lett. 2007, 48, 6352 and references therein.

24. Crystallographic data for structure 3q, reported in this paper, have been deposited with the Cambridge Crystallographic Data Center (CCDC 649395). Copies of the data can be obtained, free of charge, on application to CCDC 12 Union Road, Cambridge CB2 1EZ, UK (Fax: [phone] or e-mail: [e-mail]).

25. Karthikeyan, G.; Can. J. Chem. 2005, 83, 1746.

26. Karthikeyan, G.; Angew. Chem., Int. Ed. 2006, 45, 4659.

27. Karthikeyan, G.; Dopov. Nats. Akad. Nauk Ukr. 2002, 10, 141.

28. Gerus, I. I.;Gorbunova, M. G.; Vdovenko, S. I.; Yagupol'skii , Yu. L.; Kukhar, V. P.; J. Org. Chem. USSR (Engl. Transl.) 1990, 26, 1877.

29. Krasovsky, A. L.; Nenajdenko V. G.; Balenkova, E. S.; Russ. Chem. Bull. 2001, 50, 1395.

30. Hojo, M.; Masuda R.; Okada, E.; Tetrahedron Lett. 1989, 30, 6173.

31. Hojo, M.; Masuda R; Okada, E.; Zeitschr. Chemie 1985, 25, 21.

32. Ringel, C.; J. Prakt. Chem. 1964, 26, 5.

Received: September 3, 2007

Web Release Date: November 22, 2007

Publication Dates

• Publication in this collection
  12 Feb 2008
• Date of issue
  2007

History

• Accepted
  22 Nov 2007
• Received
  03 Sept 2007