Simultaneous regioselective synthesis of trifluoromethyl-containing 1,7-phenanthrolines and quinolines from cyclocondensation reaction of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines

Abstracts

This paper reports interesting results of the conventional synthesis of a new series of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40% yields, from cyclization reactions of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C6H4-(NHCR=CHC(O)CF3)2] in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7-aminoquinolines, in 20-73% yields, simultaneously. The enaminone precursors were obtained from the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF3C(O)CH=C(R)OR¹, where R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl and R¹ = Me, Et] with 1,3-phenylenediamine under mild conditions, in 47-91% yields.

enones; enaminoketones; phenanthrolines; quinolines; PPA

Este trabalho relata interessantes resultados relativos a síntese convencional de uma nova série de 2,10-dialquil(aril)-4,8-bis (trifluorometil)-1,7-fenantrolinas, em rendimentos de 22-40%, a partir das reações de ciclização de N,N'-bis(oxotrifluoralquenil)-1,3-fenilenodiaminas [1,3-C6H4-(NHCR=CHC(O)CF3)2] em um meio fortemente ácido (PPA) e na ausência de solvente. A rota sintética também permitiu o isolamento simultâneo de uma nova série de 2-alquil(aril/heteroaril)-4-trifluormetil-7-aminoquinolinas, em 20-73% de rendimento. As enaminonas precursoras foram obtidas a partir da reação de 4-alcóxi-1,1,1-triflúor-3-alquen-2-onas [CF3C(O)CH=C(R)OR¹, onde R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furil e R¹ = Me, Et] com 1,3-fenilenodiamina em condições brandas, em rendimentos 47-91%.

ARTICLE

Simultaneous regioselective synthesis of trifluoromethyl-containing 1,7-phenanthrolines and quinolines from cyclocondensation reaction of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines

Helio G. Bonacorso^*; Rosália Andrighetto; Nícolas Krüger; Marcos A. P. Martins; Nilo Zanatta

Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria-RS, Brazil

ABSTRACT

This paper reports interesting results of the conventional synthesis of a new series of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40% yields, from cyclization reactions of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C₆H₄-(NHCR=CHC(O)CF₃)₂] in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7-aminoquinolines, in 20-73% yields, simultaneously. The enaminone precursors were obtained from the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF₃C(O)CH=C(R)OR¹, where R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO₂Ph, 2-furyl and R¹ = Me, Et] with 1,3-phenylenediamine under mild conditions, in 47-91% yields.

Keywords: enones, enaminoketones, phenanthrolines, quinolines, PPA

RESUMO

Este trabalho relata interessantes resultados relativos a síntese convencional de uma nova série de 2,10-dialquil(aril)-4,8-bis (trifluorometil)-1,7-fenantrolinas, em rendimentos de 22-40%, a partir das reações de ciclização de N,N'-bis(oxotrifluoralquenil)-1,3-fenilenodiaminas [1,3-C₆H₄-(NHCR=CHC(O)CF₃)₂] em um meio fortemente ácido (PPA) e na ausência de solvente. A rota sintética também permitiu o isolamento simultâneo de uma nova série de 2-alquil(aril/heteroaril)-4-trifluormetil-7-aminoquinolinas, em 20-73% de rendimento. As enaminonas precursoras foram obtidas a partir da reação de 4-alcóxi-1,1,1-triflúor-3-alquen-2-onas [CF₃C(O)CH=C(R)OR¹, onde R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO₂Ph, 2-furil e R¹ = Me, Et] com 1,3-fenilenodiamina em condições brandas, em rendimentos 47-91%.

Introduction

Phenanthrolines are diazaphenanthrene analogs, polycyclic aromatic hydrocarbon present in sterols, sex hormones, cardiac glycosides, bile acids and in the group of morphine alkaloids.¹ Heterocycles containing nitrogen atoms such 1,10-phenanthroline,² pyronaridine³ and chloroquine-pyrazole analogs⁴ are well known for their antimalarial activity. An example of particular interest of a non-natural antimalarial agent possessing a trifluoromethyl substituted phenanthrene skeleton is halofantrine (Figure 1), an effective drug for the treatment of malaria which possesses good therapeutic effects but some important adverse effects.⁵ Furthermore, some angular and linear N-tricyclic similar systems have also been documented to possess antiviral activity.⁶

From a synthetic point of view, phenanthrolines obtained from phenylenediamines are of particular interest since both outer rings can be constructed simultaneously.⁷ However, phenanthrolines can be also prepared from aminoquinolines.⁸ The first phenanthroline, 1,7-phenanthroline was prepared by Skraup and Vortmann⁹ in 1882 and the method continues to be one of the best methods for synthesis of 1,7-phenanthrolines. A study of the Skraup reaction, when applied to meta and paraphenylenediamines, with arsenic acid as the oxidizing agent, revealed that the double Skraup reaction can be satisfactorily applied with proper observation of important factors, such as water concentration, method and time of heating.¹⁰

Recently, Jacquelin et al.¹¹ reported the double amination of meta-diiodo and dibromobenzenes by anthranilic acid derivates using palladium and/or copper catalysis. These symmetrical and non-symmetrical phenylenediamines were submitted to a cyclization/reduction/oxidation synthetic sequence, being key precursors to polyfunctional dibenzophenanthroline carboxaldehydes.

In addition, it has been observed that the introduction of halogenated groups into organic molecules often confers significant and useful changes in their physical, chemical and biological properties.^12-14 It is well known that fluorocarbons are becoming increasingly important in the medicinal, materials and agricultural fields. It has been reported that the introduction of a trifluoromethyl and its higher homologue C_nF_2n+1 groups into a heterocycle frequently results in a much more potent activity than that of the parent compounds, a fact which is probably related to the high lipophilicity of perfluoroalkyl substituents.^13,14

The vast majority of organofluorine compounds are not natural products. Consequently, a synthetic methodology to incorporate fluorine and fluorous synthons must be optimized in order to prepare sophisticated fluoroorganic molecules on a practical scale. One of the most satisfactory methods for introducing a CF₃ group into heterocycles is via the trifluoromethylated building block approach.^12,15-28 The trifluoroacetylation of enol ethers or acetals provided, in one step and in good yields, β-alkoxyvinyl trifluoromethyl ketones 1 which proved to be useful building blocks for the synthesis of many series of heterocyclic compounds.^16,20,22-29

Of no less importance, it is also well known that enaminocarbonyl compounds represent versatile synthetic precursors, which combine the ambident nucleophilicity of enamines with the ambident electrophilicity of enones, presenting three nucleophilic and two electrophilic sites. For this reason, enaminones have found a wide application in the synthesis of various heterocycles, dyes and drugs.^22,30-32

Specifically, we have described the synthesis of N-[1-aryl(alkyl)-3-oxo-4,4,4-trifluoro(chloro)alken-1-yl]-o-phenylenediamines^23,24 from the reactions of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones with o-phenylenediamine promoting cyclization reactions for benzodiazepine and benzoimidazole derivatives.

Recently, applying the method previously described by us for the preparation of some trifluoromethyl substituted enaminoketones and their benzo[h]quinoline,²⁵ dihydrobenzo[c]acridine,²⁶ cycloalka[b]quinoline,²⁷ and 1,2,3,4-tetrahydroacridine derivatives,²⁸ we communicated the synthesis of only three examples of 2,8-and 4,8-bis(trifluoromethyl)-1,7-phenanthrolines and 4-(trifluoromethyl)-7-aminoquinolines where two interesting intramolecular cyclization routes were found when N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines were heated at 165 ºC in polyphosphoric acid medium.²⁹

The purpose of this paper is to report the complete results of the reactions of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones (1a-j) with 1,3-phenylenediamine to obtain a wide series of ten examples of trifluoroacetyl substituted 1,3-phenylene-bis-enamines (2a-j) and also to investigate the chemical behavior of alkyl, aryl and heteroaryl-substituted enamino intermediates (2) for their application in the simultaneous regioselective synthesis of new 2,8- or 4,8-bis(trifluoromethyl)-2,10-bis-alkyl(aryl)-1,7-phenanthrolines (3) and the respective 4-(trifluoromethyl)-7-aminoquinolines (4) under similar reaction conditions as described previously.²⁹

Results and Discussion

Firstly, a series of ten examples of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones (1a-j), which are readily available 1,3-dielectrophiles (CCC synthetic blocks), were prepared from trifluoroacetylation reactions of enol ethers commercially available (for 1a-b) or generated in situ from the respective acetophenone dimethyl acetal (for 1c-j) with trifluoroacetic anhydride, respectively, in the presence of pyridine, as described in the literature.³³

Second, a new series of ten bis-enaminone intermediates 2a-j was isolated in satisfactory yields of 47-91%, by the reaction of enones 1a-j with 1,3-phenylenediamine at a molar ratio of 2:1, respectively (Scheme 1). The reactions can now be carried out in ethanol, water, water/dichloromethane (1:1) or water/chloroform (1:1) at a temperature range of 25 to 80 ºC (Scheme 1). The best results were obtained when enones 1a-j were added to 1,3-phenylenediamine, in pure ethanol for 1a-d and 1f-j or in water/chloroform (1:1) solution for 1e. Good yields were also obtained under other reaction conditions tested, as above described. For example, the compounds 2b and 2g were obtained in good yields (85%) when the reactions were carried out in water at room temperature as solvent. However, the syntheses of enaminones 2a, 2f and 2h were unsuccessful in an aqueous medium.

The structures of compounds 2a-j were easily established on the basis of ¹H and ¹³C NMR spectroscopy. In order to obtain structural information about the configuration of the compounds 2a-j we have performed an ¹H NMR study on (Z,Z)-N,N'-bis(3-oxo-4,4,4-trifluoro-1-buten-1-yl)-1,3-phenylenediamine (2a). The ¹H NMR spectrum of 2a in CDCl₃ showed (see SI) a cis coupling constant for the vicinal olefin protons with J ca. 8 Hz, which is consistent with a Z-configuration as the E- and Z-forms can be easily distinguished by their ¹H NMR spectra because the N-H signals of the E-form (in 4-8 ppm) appeared at a much higher field than those of the Z-form (in 9-13 ppm), indicating the presence of an intramolecular hydrogen bonding in the latter.³⁴ The ¹H NMR chemical shifts of the enamino hydrogens (NH) for 2a-j were observed on average of 12.20 ppm, allowing one to assume that the enaminones 2a-j exist in the Z,Z-configuration in CDCl₃, which is stabilized by an intramolecular hydrogen bond (N-H···OC) in each enaminone moiety. The proposed Z-configuration was confirmed also by X-ray crystal diffraction³⁵ for compound 2g (Figure 2).

In a second reaction step, the acyclic enaminones 2a-j were subjected to reactions carried out in the presence of a strongly acidic medium (polyphosphoric acid, PPA), in the absence of solvent. For all reactions, initially, PPA (P₂O₅ + H₃PO₄) was prepared at 90 ºC and the compounds 2a-j were added to the acid mixture. The cyclization of 2a-j showed that the best results were at 165 ºC for 36 h, affording the corresponding new angular series of bis-trifluoromethyl-substituted 1,7-phenanthrolines 3a-i in 22-40% yields (Scheme 2). Unfortunately, the above described general and optimized conditions allowed us to obtain only traces of the phenanthroline 3j derived from the enaminone 2j (2-furyl derivative).

According to the literature, it is known that the formation of two pyridine rings from derivatives of the 1,3-phenylenediamine may proceed in two possible ways to give a 1,7-phenanthroline (3a, 5) or a benzodipyridine (6).^8,9,29,36,37 It is also known that in the formation of cyclic compounds from phenylenediamine or quinoline derivatives, the angular structure is obtained in preference to the linear one when both are possible.^8,9,29,36 In the present work, only derivatives of the angular structure were obtained, instead of the linear isomer bis-trifluoromethyl-substituted pyrido[g]quinolines (6) (Scheme 2). However, neither of the products isolated showed a mode of cyclization similar to that observed in the product previously identified by us as 2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a).²⁹ Only the formation of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)1,7-phenanthrolines (3b-i) was observed, as shown in Scheme 2.

The structures of 3a-i were established on the basis of ¹H and ¹³C NMR spectroscopies and also confirmed by X-ray diffraction of 3a (Figure 3) and 3c (Figure 4). The structure pattern of compound 3a is different from that of 3b-i, although obtained under similar reaction conditions. For the 2,8-bis-trifluoromethyl-1,7-phenanthroline (3a) the two CF₃ groups occupy the nitrogen-adjacent positions, suggesting the occurrence of two retro 1,4-cyclocondensations (hydrolysis and recombination) at the same molecule 2a during the closure of the two pyridine rings and following a mechanism already described in the literature for a single cyclocondensation reaction, which allowed the isolation of 2-trifluoromethyl-substituted quinolines^22,37-42 and benzo[h]quinolines.^37,40

The 2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a) showed ¹³C NMR chemical shifts at 149.6 ppm (q, ²J_CF 34 Hz, C-2), 147.6 ppm (q, ²J_CF 35 Hz, C-8) and 121.5 ppm (q, ¹J_CF 275 Hz, 2 CF₃). The ¹³C NMR spectra of the compounds 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b-i) showed chemical shifts for C-4 in the range of 133.1-136.2 ppm as a quartet with ²J_CFca. 31 Hz, for C-8 in the range of 148.2-151.1 ppm as a quartet with ²J_CFca. 34 Hz, for CF₃ groups in the range of 120.6-123.4 ppm as a quartet with ¹J_CFca. 275 Hz. The 2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a) showed ¹⁹F NMR signals at -67.12 and -67.26 ppm (CF₃-2, CF₃-8). The ¹⁹F NMR spectra for compounds 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b, c, g) showed signals of CF₃-4 at an average of -60.54 ppm and for CF₃-8 at an average of -67.28 ppm. The spectroscopic data agree with ¹³C NMR and ¹⁹F NMR chemical shift data for similar compounds described in the literature.^28-31,38

From the analysis of NMR data, we observed that one ring closure occurred by a 1,2-cyclocondensation reaction, while the other occurred by a retro 1,4-cyclocondensation. Thus, one CF₃ group is attached at the nitrogen-remote position (4-CF₃) andin the second ring and the CF₃ group is occupying the nitrogen-adjacent position (8-CF₃). These two different mechanisms are involved in the synthesis of a series of 4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b-i). Compounds 3 were separated from the reaction mixture by a sublimation process during the heating of the pure enaminone precursors 2, in PPA medium.

The possible formation of the 2,10-bis(trifluoromethyl)-1,7-phenanthroline isomer (7, Scheme 2) was also excluded because the 5-amino-4-(trifluoromethyl)quinolines were not detected in the cyclization reactions from 2b-j. The possible formation of the 4,10-bis(trifluoromethyl)-1,7-phenanthroline isomer (5) was also excluded because the CF-coupling on the NMR spectra should be present as one quartet signal for the CF₃ group and two identical quartets for C-4 and C-10 in the narrow range of δ 147-150 ppm and no quartet signals should be expected in the region of δ 134-135 ppm.

On the other hand, the cyclization reactions of the enaminones 2 by heating in acidic medium (PPA) could result in the synthesis of the linear bis-trifluoromethyl-substituted pyrido[g]quinolines (6), as reported in the literature (Scheme 2).³⁷ However, the NMR spectrum should show four singlets for H-3, H-5, H-7 and H-10, which were not observed, thus excluding the formation of a linear isomer (pyrido[g]quinoline). In our case, all spectroscopic data were consistent with the proposed angular structures for phenanthrolines 3a-i, which are preferably obtained according to the literature.⁷

The 2-alkyl(aryl/heteroaryl)-7-amino-4-(trifluoro-methyl) quinolines (4b-j, Scheme 2) were obtained in 20-73% yields, as by-products, from the reported cyclization reactions and were isolated by recrystallization after the work-up of residual reaction mixtures according to the procedure described. We have attempted unsuccessfully to obtain the phenanthrolines 3j-k under milder reaction conditions than those described, but only quinoline 4j was successfully isolated. The best result for 4j was obtained when the reaction was carried out 90 ºC for 24 h (73% yield).

Linderman and Kirollos³⁸ reported the synthesis of 2-CF₃-substituted quinolines and assigned the chemical shift for the CF₃ group of the ¹³C NMR spectra as quartets at δ 122.3 ppm (¹J_CF 275 Hz, CF₃) and at δ 148.5 ppm (²J_CF 34 Hz, C2). In the same letter, another intramolecular cyclization route was also described, which allowed the synthesis of the 4-(trifluoromethyl)quinoline isomer. With the synthesis of 4-CF₃ quinolines, they reported the ¹³C NMR spectral data and assigned the chemical shift for the CF₃ group for this regioisomer as quartets at δ 124.2 ppm (¹J_CF 275 Hz, CF₃) and δ 134.8 ⁽²J_CF ppm 31 Hz, C4), respectively. In some cases, the reactionsresulted in mixtures of 2- and 4-CF₃ quinolines.

The structures of quinolines 4b-j were established on the basis of ¹H and ¹³C NMR spectroscopies and literature data for similar compounds.^36,39,40 The ¹³C NMR spectra of the compounds 2-alkyl(aryl/heteroaryl)-7-amino-4-(trifluoromethyl)quinolines (4b-j) showed chemical shifts for C-4 in the range of 130.7-134.5 ppm as a quartet with ²J_CFca. 31 Hz and for CF₃ groups in the range of 118.3-125.5 ppm as a quartet with ¹J_CFca. 275 Hz. The ¹⁹F NMR spectra of the compounds 2-alkyl(aryl/heteroaryl)-7-amino-4-(trifluoromethyl)quinolines (4b, c, g, i) showed signals of CF₃-4 at an average of -62.26 ppm.

Schlosser et al.,³⁹ who have investigated the synthesis of 2- and 4-(trifluoromethyl)quinolines and quinolinones in details, demonstrated a novel mode of isomerization and cyclization in the synthesis of 2-(trifluoromethyl)quinolines from anilines. As described, 4-anilino-l,l,l-trifluoro-3-buten-2-ones can be readily obtained from the ethyl trifluoroacetate derived 4-tert-butylamino-l,l,l-trifluorobut-3-en-2-one by simple amine/amine replacement. Upon heating in the presence of phosphoryl chloride, they undergo ring closure to afford 2-(trifluoromethyl)quinolines rather than the expected 4-isomers in 50% average yield.³⁹

In subsequent experiments, Schlosser et al.⁴¹ determined how 2-anilinovinyl perfluoroalkyl ketones can be mechanistically correlated with their cyclization products 2-(perfluoroalkyl)quinolines. Their studies demonstrated that some perfluoroalkyl-substituted 3-aminoenones, when heated in the presence of phosphoryl chloride, cleaved hydrolytically, setting free the substituted anilines and the 1,3-dicarbonyl compounds. A proved recombination of these subunits furnished unexpected 2-(CF₂)_nCF₃-quinolines.⁴¹

Then, based on experiments of Schlosser et al.⁴¹ to prove that a cleavage and a recombination reaction occurred on enaminones 2, an equimolar mixture of (Z,Z)-N,N'-bis(3-oxo-4,4,4-trifluorobut-1en-1-yl)-1,3-phenylenediamine (2a) and p-toluidine was heated at 165 ºC for 36 h in the presence of PPA. The products were identified by their gas chromatographic retention times in comparison with those of authentic samples. Thus, 65% of 6-methyl-2-(trifluoromethyl)quinoline, 25% of 2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a) and 11% of p-toluidine were identified after the reaction work-up (Scheme 3). Thus, we think that the mechanism suggested by Schlosser and co-workers may also explain the unexpected findings of our work. We also think that the starting material 2a afforded the 2,8-(CF₃) product (3a) "exclusively" but in only 32% yield, in absence of p-toluidine, because the heating in presence of PPA promoted the hydrolytic cleavage of the enaminone 2a and a latter recombination also occurred but due to the high reaction temperature (165 ºC), most of the volatile 4,4,4-trifluoro-3-oxobutanal escaped from the hot reaction mixture in the course of the recombination reaction.

The isolation of quinolines 4b-j also suggests that a hydrolysis reaction occurred in 2b-j, and the expected recombination of the precursors to allow the synthesis of phenanthrolines 3b-j, due to the high reaction temperature, did not occur totally, probably because the dicarbonyl compounds evaporated from the hot reaction mixtures.

The presented methodology used to obtain the intermediate 1,3-phenylene-bis-trifluoromethyl substituted enaminones (2a-j) showed satisfactory results. It can be affirmed through the experimental data identified by ¹H NMR and confirmed by X-ray crystal diffraction that these synthetic intermediates 2a-j have a Z-configuration. The procedure of its cyclization in strongly acidic medium (PPA) proved to be feasible for the synthesis of bis-trifluoromethyl-1,7-phenanthrolines (3a-i). The interesting results reported herein regarding the chemical behavior of these bis-enaminones 2a-j when subjected to the cyclization reaction showed that the mode of cyclization of unsubstituted bis-enaminone 2a (R¹ = H) differs from that of substituted bis-enaminones (R¹≠ H) under the same reaction conditions.

Depending on the structure of the (Z,Z)-N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines (2), 2,8-bis-(trifluoromethyl)-1,7-phenanthroline or a mixture of separable 4,8-bis-(trifluoromethyl)-1,7-phenanthrolines and 4-(trifluoromethyl)-7-aminoquinolines was obtained. These results reported here showed an interesting chemical behavior for the mechanism of cyclization of these new enaminoketones 2, showing selective routes of ring closure including direct cyclocondensations, hydrolyses and recombinations, which furnished new fused bis-(trifluoromethyl)-diazatricycles. Linear bis(trifluoromethyl)-pyrido[g]quinolines (6) compounds were not isolated.

Conclusions

In summary, we have described an inexpensive and unique route to prepare 1,7-phenanthroline and 7-aminoquinoline cores simultaneously. This process might lead to greater molecular diversity of both heterocyclic series, which are of great potential interest for pharmacological and material applications.

Experimental

General

Unless otherwise indicated, all common reagents and solvents were used as obtained from commercial suppliers without further purification. The melting points (mp) were determined using a Kofler Reichert-Thermovar and Electrothermal Mel-Temp 3.0 apparatus. ¹H, ¹³C and ¹⁹F NMR spectra were acquired on a Bruker DPX 200 spectrometer (¹H at 200.13 MHz) and Bruker DPX 400 (¹H at 400.13 MHz, ¹³C at 100.32 MHz and ¹⁹F at 376.3 MHz) spectrometer, 5 mm sample tubes, 298 K, digital resolution of ± 0.01 ppm, in CDCl₃ for 1, 2, 3 and in DMSO-d₆ for 4, using TMS as internal reference (¹H and ¹³C) or fluorobenzene as external reference (¹⁹F). Mass spectra (MS) were registered in a HP 6890 GC connected to a HP 5973 MSD and interfaced by a Pentium PC. The gas chromatograph (GC) was equipped with a split-splitless injector, autosampler, cross-linked HP-5 capillary column (30 m, 0.32 mm of internal diameter), and helium was used as the carrier gas. The diffraction (XRD) measurements were carried out by graphite-monochromatized Mo Kα radiation with λ 0.71073 Å on a Bruker SMART CCD diffractometer.⁴³ The structures of 2g, 3a and 3c were solved with direct methods using SHELXS-97 program,⁴⁴ and refined on F² by full-matrix least-squares by the SHELXL-97 package.⁴⁵ The absorption correction was performed by Gaussian methods.⁴⁶ Anisotropic displacement parameters for non-hydrogen atoms were applied. The hydrogen atoms were placed at calculated positions with 0.96 Å (methyl CH₃), 0.97 Å (methylene CH₂), 0.98 Å (methyne CH), 0.93 Å (aromatic CH) using a riding model. The hydrogen isotropic thermal parameters were kept equal to Uiso(H) = χUeq (carrier C atom), with χ = 1.5 for methyl groups and χ = 1.2 otherwise. The valence angles C-C-H and H-C-H of methyl groups were set to 109.5º and the H atoms were allowed to rotate around the C-C bond. A molecular graph was prepared using ORTEP3 for Windows.⁴⁷ The CHN elemental analyses were performed on a Perkin-Elmer 2400 CHN elemental analyzer (São Paulo University, USP/Brazil).

General procedure for the synthesis of N,N'-bis(1-alkyl[aryl(heteroaryl)]-4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamines (2a-j)

To a stirred solution of 1,3-phenylenediamine (0.54 g, 5 mmol) in ethanol (10 mL), 1a-j (10 mmol) was added at room temperature. The mixture was stirred at 40 ºC for 2 h. After the end of the reaction (TLC), the resulting solid products 2a-j were isolated by filtration (1^st fraction: 80%). Subsequently, the filtrates were evaporated under reduced pressure and the residues were dissolved in hot chloroform and stirred with activated charcoal. After filtration, the filtrates were evaporated under reduced pressure. Then, the crude oily products 2 were dissolved in hot ethanol and subsequently cooled (4-8 ºC, 48 h) to give 2 as powders (2^nd fraction: 20%). Finally, both fractions were combined and gathered and recrystallized from chloroform (26-91% yields).

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-3-oxo-1-buten-1-yl)1,3-phenylenediamine (2a) ³²

Beige solid (1.20 g, 68% yield); mp 171-173 ºC; ¹H NMR (CDCl₃) δ 11.74 (d, 2H, J 12 Hz, NH), 7.63 (dd, 2H, J₁ 8, J₂ 12 Hz, H-1), 7.41 (t, 1H, J 8 Hz, H-9), 6.95 (dd, H-8, J₁ 2, J₂ 8 Hz, 2H, H-10), 6.86 (t, 1H, J 2 Hz, H-6),5.71 (d, 2H, J 8 Hz, H-2); ¹³C NMR (CDCl₃) δ 179.3 (q, ²J 34 Hz, 2 C-3), 149.3 (2 C-1), 140.3 (2 C, C-5, C-7), 131.3 (C-6), 116.5 (q, ¹J 289 Hz, 2 CF₃), 113.8 (2 C, C-8, C-10),105.7 (C-9), 90.3 (2 C-2); ¹⁹F (CDCl₃) δ -75.35 (2-CF₃); GC-MS (EI, 70 eV, m/z) 352 (M⁺, 100), 283 (55), 213 (23), 185 (33), 107 (24), 263 (11), 69 (5%); Anal. calcd. for C₁₄H₁₀F₆N₂O₂ (352.06): C, 47.74; H, 2.86; N, 7.95%. Found: C, 48.03; H, 2.96; N, 7.85%.

(Z,Z)-N,N'-bis(5,5,5-Trifluoro-4-oxo-2-penten-2-yl)1,3-phenylenediamine (2b)

Brown solid (1.63 g, 86% yield); mp 126-128 ºC; ¹H NMR (CDCl₃) δ 12.58 (s, 2H, NH), 7.48 (t, 1H, J 8 Hz, H-9), 7.14 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 7.01 (s, 1H, H-6), 5.59 (s, 2H, H-2), 2.15 (s, 6H, CH₃); ¹³C NMR (CDCl₃) δ 177.1 (q, ²J 34 Hz, 2 C-3), 167.2 (2 C-1), 138.2 (2 C, C-5, C-7), 130.5 (C-6), 123.8 (2 C, C-8, C-10), 121.7 (C-9), 117.2 (q, ¹J 288 Hz, 2 CF₃), 91.5 (q, ³J 1 Hz, 2 C-2),20.3 (2 CH₃); GC-MS (EI, 70 eV, m/z) 199 (100), 380 (M⁺, 75), 311 (40), 283 (55), 265 (48), 69 (7%); Anal. calcd. for C₂₆H₁₄F₆N₂O₂ (380.10): C, 50.53; H, 3.71; N, 7.37%.Found: C, 50.85; H, 3.81; N, 7.61%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-phenyl-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2c)

Yellow solid (2.01 g, 80% yield); mp 190-192 ºC; ¹H NMR (CDCl₃) δ 12.20 (s, 2H, NH), 7.49-7.19 (m, 10H, Ph), 6.94 (t, 1H, J 8 Hz, H-9), 6.52 (d, 2H, J 8 Hz, H-8, H-10), 6.40 (s, 1H, H-6), 5.70 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.1 (q, ²J 34 Hz, 2 C-3), 166.1 (2 C-1), 138.8 (2 C, C-5, C-7), 133.5 (2 C-Ph), 130.9 (C-6), 129.4, 128.8,128.2 (10 C-Ph), 121.7 (2 C, C-8, C-10), 119.5 (C-9), 117.15 (q, ¹J 289 Hz, 2 CF₃), 93.1 (2 C-2); GC-MS (EI, 70 eV, m/z) 504 (M⁺, 30), 435 (22), 407 (100), 323 (30), 69 (2%); Anal. calcd. for C₂₆H₁₈F₆N₂O₂ (504.13): C, 61.91;H, 3.60; N, 5.55%. Found: C, 62.02; H, 3.75; N, 5.64%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-[4-methylphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2d)

Brown solid (2.29 g, 86% yield); mp 138-140 ºC; ¹H NMR (CDCl₃) δ 12.20 (s, 2H, NH), 7.12 (d, 4H, J 8 Hz, Ph), 7.16 (d, 4H, J 8 Hz, Ph), 6.96 (t, J 8 Hz, 1H, H-9),6.54 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.41 (s, 1H, H-6),5.69 (s, 2H, H-2), 2,33 (s, 6H, 2 CH₃); ¹³C NMR (CDCl₃) δ 178.0 (q, ²J 34 Hz, 2 C-3), 166.3 (2 C-1), 141.6 (2 C-Ph),139.2 (2 C, C-5, C-7), 130.7 (C-6), 129.5, 129.4, 128.3 (10 C-Ph), 121.6 (2 C, C-8, C-10), 119.5 (C-9), 117.3 (q, ¹J 289 Hz, 2 CF₃), 93.0 (2 C-2), 21.3 (2 CH₃); GC-MS (EI, 70 eV, m/z) 435 (100), 532 (M⁺, 21), 463 (17), 351 (21), 222 (15), 69 (5%); Anal. calcd. for C₂₈H₂₂F₆N₂O₂(532.16): C, 63.16; H, 4.16; N, 5.26%. Found: C, 63.02; H, 4.21; N, 5.30%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-[4-methoxyphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2e)

To a stirred solution of 1,3-phenylenediamine (0.54 g, 5 mmol) in H₂O:CHCl₃ (1:1, 10 mL), 1e (2.60 g, 10 mmol) was added at room temperature. The mixture was stirred for 4 h at 60 ºC. After the end of the reaction (TLC), the resulting residue was extracted with dichloromethane. Then the organic layer was evaporated under reduced pressure. Then, the crude oily product was dissolved in hot ethanol and subsequently cooled (4-8 ºC, 48 h) to give the title compound 2e.

Beige solid (1.32 g, 47% yield), mp 142-144 ºC; ¹H NMR (CDCl₃) δ 12.22 (s, 2H, NH), 7.19 (d, 4H, J 9 Hz, Ph), 6.98 (t, 1H, J 8 Hz, H9), 6.85 (d, 4H, J 9 Hz, Ph), 6.55 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.48 (s, 1H, H-6), 5.69 (s, 2H, H-2), 3.84 (s, 6H, 2 OCH₃); ¹³C NMR (CDCl₃) δ 177.6 (q, ²J 34 Hz, 2 C-3), 165.9 (2 C-1), 161.8 (2 C-Ph), 139.3 (2 C, C-5, C-7), 130.1 (4 C-Ph), 129.5 (C-6), 125.3 (2 C-Ph), 121.7 (2 C, C-8, C-10), 119.5 (C-9),114.2 (4 C-Ph), 117.1 (q, ¹J 289, 2 CF₃), 92.7 (2 C-2), 55.4 (2 OCH₃); GC-MS (EI, 70 eV, m/z) 564 (M⁺, 21), 281 (70), 207 (100), 96 (10%); Anal. calcd. for C₂₈H₂₂F₆N₂O₄(564.15): C, 59.58; H, 3.93; N, 4.96%. Found: C, 59.55; H, 3.89; N, 4.98%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-[4-fluorophenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2f)

Beige solid (1.67 g, 62% yield); mp 177-179 ºC; ¹H NMR (CDCl₃) δ 12.20 (s, 2H, NH), 7.28-7.21 (m, 4H, Ph), 7.11-6.95 (m, 4H, Ph), 6.98 (t, 1H, J 8 Hz, H9), 6.53 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.51 (s, 1H, H-6), 5.69 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.1 (q, ²J 34 Hz, 2 C-3),163.9 (d, ¹J 253 Hz, 2 C-FPh), 164.9 (2 C-1), 138.9 (2 C, C-5, C-7), 130.5 (d, ³J 9 Hz, 4 C-FPh), 129.6 (C-6), 129.5 (d, ⁴J 3 Hz, 2 C-FPh), 122.0 (2 C, C-8, C-10), 119.7 (C-6),117.0 (q, ¹J 289 Hz, 2 CF₃), 116.1 (d, ²J 22 Hz, 4 C-FPh),93.2 (2 C-2);GC-MS (EI, 70 eV, m/z) 540 (M⁺, 20), 471 (20), 443 (100), 255 (30), 226 (30), 69 (10%); Anal. calcd. for C₂₆H₁₆F₈N₂O₂ (540.11): C, 57.79; H, 2.98; N, 5.18%.Found: C, 57.63; H, 2.99; N, 5.19%.

(Z,Z)-N,N'-[1-[4-Chlorophenyl]-4,4,4-trifluoro-3-oxo--1-yl]-1,3-phenylenediamin1-buten-1-yl]-1,3-phenylenediamine (2g)

Brown solid (2.37 g, 83% yield); mp 175-177 ºC; ¹H NMR (CDCl₃) δ 12.16 (s, 2H, NH), 7.34 (d, 4H, J 9 Hz, Ph), 7.17 (d, 4H, J 9 Hz, Ph), 6.99 (t, 1H, J 8 Hz, H-9),6.53 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.50 (s, 1H, H-6),5.68 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.2 (q, ²J 34 Hz, 2 C-3), 164.6 (2 C-1), 138.8 (2 C, C-5, C-7), 131.9 (C-6), 129.8, 129.7, 129.6, 129.2, 128.9 (12 C-Ph), 122.2 (2 C, C-8, C-10), 119.7 (C-9), 116.9 (q, ¹J 289 Hz, 2 CF₃), 93.2 (2 C-2); GC-MS (EI, 70 eV, m/z) 572 (M⁺, 17), 475 (100), 433 (7), 391 (34), 242 (30), 213 (4), 69 (5%); Anal. calcd. for C₂₆H₁₆F₆N₂O₂ (572.05): C, 54.54; H, 2.79; N, 4.89%.Found: C, 54.57; H, 2.87; N, 4.99%.

(Z,Z)-N,N'-bis(1-[4-Bromophenyl]-4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2h)

Beige solid (3.00 g, 91% yield); mp 170-172 ºC; ¹H NMR (CDCl₃) δ 12.20 (s, 2H, NH), 7.51 (d, 4H, J 9 Hz, Ph), 7.10 (d, 4H, J 9 Hz, Ph), 6.99 (t, 1H, J 8 Hz, H-9), 6.53 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.51 (s, 1H, H-6), 5.69 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.4 (q, ²J 34 Hz, 2 C-3), 164.7 (2 C-1), 138.9 (2 C, C-5, C-7), 132.4, 132.2, 131.0, 129.8 (12 C-Ph), 125.6 (C-6), 122.2 (2 C, C-8, C-10), 119.7 (C-9), 116.6 (q, ¹J 289 Hz, 2 CF₃),93.3 (2 C-2); GC-MS (EI, 70 eV, m/z) 659 (M⁺, 17), 549 (100), 286 (30), 69 (9%); Anal. calcd. for C₂₆H₁₆Br₂F₆N₂O₂(659.95): C, 47.16; H, 2.44; N, 4.23%. Found: C, 47.25; H, 2.45; N, 4.34%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-(4-nitrophenyl)-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2i)

Beige solid (2.64 g, 89% yield); mp 220-222 ºC; ¹H NMR (CDCl₃) δ 12.13 (s, 2H, NH), 8.24 (dd, 4H, J 2, J 8 Hz, Ph), 7.45 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph), 6.95 (t, 1H, J 8 Hz, H-9), 6.58 (t, 1H, J 2 Hz, H-6), 6.46 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 5.74 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.5 (q, ²J 34 Hz, 2 C-3), 165.4 (2 C-1), 146.3, 145.9 (4 C-Ph), 138.8 (2 C, C-5, C-7), 132.2, 129.7 (8 C-Ph),125.6 (C-6), 122.2 (2 C, C-8, C-10), 119.8 (C-9), 117.2 (q, ¹J 289 Hz, 2 CF₃), 92.9 (2 C-2); GC-MS (EI, 70 eV, m/z) 594 (M⁺, 15), 525 (30), 497 (100), 69 (10%); Anal. calcd. for C₂₆H₁₆F₆N₄O₆ (594.10): C, 52.54; H, 2.71; N, 9.43%.Found: C, 52.60; H, 2.70; N, 9.47%.

(Z,Z)-N,N'-bis(4,4,4-Trifluoro-1-[2-furyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2j)

Yellow solid (1.72 g, 71% yield); mp 210-212 ºC; ¹H NMR (CDCl₃) δ 12.23 (s, 2H, NH), 7.46 (s, 2H, furyl),7.34 (t, 1H, J 8 Hz, H-9), 7.04 (dd, 2H, J₁ 2, J₂ 8 Hz, H-8, H-10), 6.83 (s, 1H, H-6), 6.45-6.41 (m, 4H, furyl), 6.09 (s, 2H, H-2); ¹³C NMR (CDCl₃) δ 178.2 (q, ²J 34 Hz, 2 C-3),153.9 (2 C-1), 145.8, 145.6 (4 C-furyl), 139.7 (2 C, C-5, C-7), 130.1 (C-6), 123.6 (2 C, C-8, C-10), 121.4 (C-9),117.3 (q, ¹J 288 Hz, 2 CF₃), 117.2, 112.6 (4 C-furyl), 89.2 (2 C-2); GC-MS (EI, 70 eV, m/z) 484 (M⁺, 15), 415 (21), 387 (100), 227 (14), 69 (7%); Anal. calcd. for C₂₂H₁₄F₆N₂O₄(484.09): C, 54.55; H, 2.91; N, 5.78%. Found: C, 54.57; H, 2.90; N, 5.82%.

General procedure for the synthesis of 2,8-bis(trifluoromethyl)-1,7-phenantroline (3a), 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b-i) and 2-alkyl(aryl)-7-aminoquinolines (4b-i)

To a stirred mixture of H₃PO₄ (2 mL) and P₂O₅ (3 g) (PPA) at 90 ºC, 2a-j (2 mmol) was added. Using a 10 cm length glass adapter connecting the flask reaction and the condenser, the mixture was stirred at 165 ºC for 36 h. After this time, the sublimated products 3a-i were recovered from the adapter using chloroform and the remaining amounts of 3 in the reaction flask were also extracted with chloroform. Both organic fractions were recrystallized from chloroform (22-40% yields). To the dark residue remainder in the reaction flask were added 20 g of crushed ice and ethyl acetate (20 mL). After stirring, the 7-aminoquinolines (4b-j) were isolated when the aqueous phase was extracted with ethyl acetate (6 × 20 mL) combined with NaOH sol. 40% (5 mL). The organic layer was washed with distilled water (3 × 15 mL) and dried over sodium sulfate. After filtration, the liquid phase was stirred and heated in the presence of activated charcoal, filtered again and the solvent was removed under reduced pressure. The resulting powders (4b-j) were recrystallized from a mixture of ethyl acetate/hexane (3:1 v/v) (20-45% yields).

2,8-bis(Trifluoromethyl)-1,7-phenantroline (3a) ³²

Yellow solid (0.20 g, 32% yield); mp 131-133 ºC; ¹H NMR (CDCl₃) δ 9.79 (d, 1H, J 9 Hz, H-10), 8.48 (d, 1H, J 8 Hz, H-4), 8.27 (d, 1H, J 9 Hz, H-3), 8.11 (d, 1H, J 9 Hz, H-9), 8.03 (d, 1H, J 8 Hz, H-5), 8.01 (d, 1H, J 8 Hz, H-6); ¹³C NMR (CDCl₃) δ 149.6 (q, ²J 35 Hz, C-2), 149.0 (C-10b),147.6 (q, ²J 35 Hz, C-8), 144.6 (C-6a), 137.8 (C-10), 135.2 (C-4), 130.9 (C-6), 129.7 (C-5), 128.0 (C-10a), 127.9 (C-4a), 121.5 (q, ¹J 275 Hz, 2 CF₃), 119.2 (C-3), 118.4 (C-9); GC-MS (EI, 70 eV, m/z) 316 (M⁺, 100), 297 (16), 247 (77), 227 (17), 177 (28), 69 (5%); Anal. calcd. forC₁₄H₆F₆N₂ (316.20): C, 53.18; H, 1.91; N, 8.86%. Found: C, 53.34; H 2.01; N, 8.91%.

4, 8-bis(Trifluoromethyl)-2, 10-di(4-methoxyphenyl)-1, 7-phenanthroline (3b)³²

Yellow solid (0.26 g, 38% yield); mp 147-149 ºC; ¹H NMR (CDCl₃) δ 8.23 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 8.15 (d, 1H, J 8 Hz, H-6), 7.74 (s, 1H, H-3), 7.70 (s, 1H, H-9), 3.33 (s, 3H, CH₃), 2.86 (s, 3H, CH₃); ¹³C NMR (CDCl₃) δ 157.1 (C-10), 151.5 (C-2), 149.6 (C-10b), 148.0 (C-6a), 147.6 (q, ²J 34 Hz, C-8), 134.3 (q, ²J 31 Hz, C-4), 130.5 (C-10a), 126.5 (C-6), 125.2 (q, ⁴J 3 Hz, C-5), 121.6 (q, ³J 5 Hz, C-3), 120.0 (C-4a), 124.0 (q, ¹J 275 Hz, CF₃), 123.4 (q, ¹J 275 Hz, CF₃),118.5 (q, ³J 5 Hz, C-9), 27.2 (CH₃), 25.1 (CH₃); ¹⁹F NMR (CDCl₃) δ -60.36 (CF₃-4), -67.34 (CF₃-8); GC-MS (EI, 70 eV, m/z) 344 (M⁺, 100), 325 (19), 275 (19), 172 (8), 69 (6%); Anal. calcd. for C₁₆H₁₀F₆N₂(344.25): C, 55.77; H, 2.90; N,8.13%. Found: C, 55.48; H, 3.14; N, 8.03%.

4, 8 - bis (Trifluorome thyl)-2, 10 - di(phenyl)-1,7-phenanthroline (3c)

Yellow solid (0.37 g, 40% yield); mp 226-228 ºC; ¹H NMR (CDCl₃) δ 8.39 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 8.32 (d, 1H, J 9 Hz, H-6), 8.27 (s, 1H, H-3), 7.80 (s, 1H, H-9), 7.50-7.41 (m, 5H, Ph), 7.39-7.25 (m, 5H, Ph); ¹³C NMR (CDCl₃) δ 154.4 (C-10), 152.6 (C-2), 150.2 (C-10b), 148.2 (q, ²J 34 Hz, C-8), 146.7 (C-6a), 143.5, 136.7 (2 C-Ph), 135.2 (q, ²J 31 Hz, C-4), 130.7 (C-10a), 130.1, 128.7, 128.6, 127.7 (10 C-Ph), 127.3 (C-6), 127.2 (C-5), 123.4 (q, ¹J 275 Hz, CF₃), 122.3 (q, ³J 5 Hz, C-3), 122.0 (C-4a), 121.4 (q, ¹J 275 Hz, CF₃), 115.5 (q, ³J 5 Hz, C-9); ¹⁹F NMR (CDCl₃) δ -60.40 (CF₃-4), -67.38 (CF₃-8); GC-MS (EI, 70 eV, m/z) 468 (M⁺, 100), 449 (12), 399 (37), 226 (20), 198 (19), 137 (5%); Anal. calcd. for C₂₆H₁₄F₆N₂ (468.11): C, 66.67; H, 3.01;N, 5.98%. Found: C, 66.71; H, 3.25; N, 6.04%.

4,8-bis(Trifluoromethyl)-2,10-di(4-methylphenyl)-1,7-phenanthroline (3d)

Yellow solid (0.32 g, 28% yield); mp 230-232 ºC; ¹H NMR (CDCl₃) δ 8.00 (d, 4H, J 8 Hz, Ph), 7.86 (d, 1H, J₂ 9 Hz, H-6), 7.82 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.84 (s, 1H, H-3), 7.72 (s, 1H, H-9), 7.32 (d, 4H, J 8 Hz, Ph), 2.47 (s, 3H, CH₃), 2.42 (s, 3H, CH₃); ¹³C NMR (CDCl₃) δ 155.3 (C-10),153.5 (C-2), 151.1 (C-10b), 149.6 (q, ²J 34 Hz, C-8), 147.5 (C-6a), 139.8, 136.7 (4 C-Ph), 135.2 (q, ²J 31 Hz, C-4),130.1 (C-10a), 129.5, 128.3 (8 C-Ph), 125.9 (C-6), 123.4 (q, ¹J 275 Hz, CF₃), 121.4 (q, ¹J 275 Hz, CF₃), 120.5 (C-5),120.1 (C-4a) 117.4 (q, ³J 3 Hz, C-3), 115.5 (q, ³J 5 Hz, C-9), 22.9 (CH₃), 21.1(CH₃); GC-MS (EI, 70 eV, m/z) 496 (M⁺, 100), 477 (10), 427 (35%); Anal. calcd. for C₂₈H₁₈F₆N₂ (496.14): C, 67.74; H, 3.65; N, 5.64%. Found: C, 67.81; H, 3.74; N, 5.68%.

4,8-bis(Trifluoromethyl)-2,10-di(4-methoxyphenyl)1,7-phenanthroline (3e)

Yellow solid (0.23 g, 22% yield); mp 246 -248 ºC; ¹H NMR (CDCl₃) δ 8.15 (dd, J₁ 2, J₂ 8 Hz, 4H, Ph), 8.97 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.12 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph),7.08 (d, 1H, J 2 Hz, H-6), 6.98 (s, 2H, H-3, H-9), 3.89 (s, 6H, OCH₃); ¹³C NMR (CDCl₃) δ 155.5 (C-10), 153.7 (C-2),151.3 (C-10b), 149.2 (q, ²J 34 Hz, C-8), 147.7 (C-6a), 144.5 (2 C-Ph), 136.2 (q, ²J 31 Hz, C-4), 132.7 (C-10a), 130.8,130.6 (6 C-Ph), 129.8 (C-6), 129.4 (C-5), 128.0 (q, ³J 5 Hz, C-3), 127.6 (C-4a), 124.9 (4 C-Ph), 124.0 (q, ¹J 275 Hz, CF₃), 122.8 (q, ¹J 275 Hz, CF₃), 117.6 (q, ³J 5 Hz, C-9), 54.5 (OCH₃), 52.3 (OCH₃); GC-MS (EI, 70 eV, m/z) 528 (M⁺, 100), 509 (14), 459 (38%); Anal. calcd. for C₂₈H₁₈F₆N₂O₂(528.13): C, 63.64; H, 3.43; N, 5.30%. Found: C, 63.59; H, 3.38; N, 5.41%.

4,8-bis(Trifluoromethyl)-2,10-di(4-fluorophenyl)-1,7-phenanthroline (3f)

Yellow solid (0.29 g, 29% yield); mp 234-236 ºC; ¹H NMR (CDCl₃) δ 8.15-8.08 (m, 2H, Ph), 7.86 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.76 (s, 1H, H-6), 7.43-7.39 (m, 2H, Ph), 7.23 (s, 1H, H-3), 7.19-7.14 (m, 2H, Ph), 7.01 (s, 1H, H-9), 7.01-6.94 (m, 2H, Ph); ¹³C NMR (CDCl₃) δ 162.3 (d, ¹J 253 Hz, 2 C-FPh), 155.1 (C-10), 154.2 (C-2), 153.3 (C-10b), 148.6 (q, ²J 34 Hz, C-8), 146.1 (C-6a), 133.1(q, ²J 31 Hz, C-4), 130.3 (d, ⁴J 3 Hz, 2 C-FPh), 129.1 (C-10a), 128.3 (d,³J 8 Hz, 4 C-FPh), 122.2 (C-6), 123.4 (q, ¹J 275 Hz, CF₃), 121.4 (q, ¹J 275 Hz, CF₃), 117.6 (q, ³J 5 Hz, C-5), 115.4 (C-4a), 114.4 (d, ²J 22 Hz, 4 C-FPh), 114.2 (C-3), 112.8 (C-9); GC-MS (EI, 70 eV, m/z) 503 (M⁺, 100), 485 (7), 435 (18), 409 (16%); Anal. calcd. for C₂₆H₁₂F₈N₂(504.09): C, 61.91; H, 2.40; N, 5.55%. Found: C, 61.95; H, 2.53; N, 5.64%.

2,10-di(4-Chlorophenyl)-4,8-bis(trifluoromethyl)1,7-phenanthroline (3g)

Yellow solid (0.37 g, 35% yield); mp 236-238 ºC; ¹H NMR (CDCl₃) δ 8.39 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 8.34 (d, 1H, J 2 Hz, H-6), 8.23 (s, 1H, H-3), 7.76 (s, 1H, H-9), 7.49-7.46 (m, 2H, Ph), 7.37-7.35 (m, 4H, Ph), 7.24-7.21 (m, 2H, Ph); ¹³C NMR (CDCl₃) δ 153.2 (C-10), 152.5 (C-2), 151.6 (C-10b), 151.1 (q, ²J 34 Hz, C-8), 148.2 (C-6a), 137.8, 135.3 (4 C-Ph), 134.1 (q, ²J 31 Hz, C-4),131.5 (C-10a), 130.9, 169.7 (8 C-Ph), 128.0 (C-6), 126.4 (C-5), 123.6 (q, ¹J 275 Hz, CF₃), 121.5 (q, ¹J 275 Hz, CF₃),119.5 (q, ³J 5 Hz, C-3), 119.3 (C-4a), 118.1 (q, ³J 5 Hz, C-9); ¹⁹F NMR (CDCl₃) δ -60.59 (CF₃-4), -67.57 (CF₃-8); GC-MS (EI, 70 eV, m/z) 535 (M⁺, 100), 501 (20), 467 (12), 425 (12), 232.6 (14), 198 (14), 138 (5%); Anal. calcd. forC₂₆H₁₄F₆N₂ (536.02): C, 58.12; H, 2.25; N, 5.21%. Found:C, 58.21; H, 2.32; N, 5.18%.

2,10-di(4-Bromophenyl)-4,8-bis(trifluoromethyl)-1,7-phenanthroline (3h)

Yellow solid (0.43 g, 33% yield); mp 262-264 ºC; ¹H NMR (CDCl₃) δ 8.35 (s, 1H, H-3), 8.22 (s, 1H, H-9),7.95 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.78 (d, 1H, J 2 Hz, H-6),7.58 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph), 7.21 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph); ¹³C NMR (CDCl₃) δ 152.8 (C-10), 152.2 (C-2), 151.2 (C-10b), 149.3 (q, ²J 34 Hz, C-8), 137.5 (C-6a), 134.9 (2 C-Ph), 133.8 (q, ²J 31 Hz, C-4), 132.0 (C-10a), 131.2, 130.6, 129.3 (10 C-Ph), 127.7 (C-6), 125.6 (C-5), 123.5 (q, ¹J 275 Hz, CF₃), 121.5 (q, ¹J 275 Hz, CF₃), 119.4 (q, ³J 5 Hz, C-3), 118.9 (C-4a), 117.8 (q, ³J 5 Hz, C-9); GC-MS (EI, 70 eV, m/z) 625 (M⁺, 100), 554 (23), 468 (5), 69 (8%); Anal. calcd. for C₂₆H₁₂Br₂F₆N₂ (623.93): C, 49.87; H, 1.93;N, 4.47%. Found: C, 49.83; H, 2.01; N, 4.58%.

4,8-bis(Trifluoromethyl)-2,10-di(4-nitrophenyl)-1,7-phenanthroline (3i)

Yellow solid (0.29 g, 23% yield); mp 249-251 ºC; ¹H NMR (CDCl₃) δ 8.37 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph), 8.12 (dd, 4H, J₁ 2, J₂ 8 Hz, Ph), 7.97 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.90 (s, 1H, H-3), 7.37 (s, 1H, H-9), 7.13 (dd, 1H, J₁ 2, J₂ 8 Hz, H-6); ¹³C NMR (CDCl₃) δ 155.5 (C-10),153.9 (C-2), 152.0 (C-10b), 150.4 (q, ²J 34 Hz, C-8),147.8 (C-6a), 147.4, 143.9 (4 C-Ph), 134.3 (q, ²J 31 Hz, C-4), 131.4 (C-10a), 130.0 (4 C-Ph), 126.5 (C-6), 125.2 (q, ⁴J 3 Hz, C-5), 124.5 (4 C-Ph), 123.4 (q, ¹J 275 Hz, CF₃),121.5 (q, ¹J 275 Hz, CF₃), 121.6 (q, ³J 5 Hz, C-3), 120.9 (C-4a), 118.4 (q, ³J 5 Hz, C-9); GC-MS (EI, 70 eV, m/z) 558 (M⁺, 100), 539 (18), 489 (30), 69 (10%); Anal. calcd. for C₂₆H₁₂F₆N₄O₄(558.08): C, 55.92; H, 2.17, N; 10.03%.Found: C, 55.88; H, 2.28; N, 10.21%.

4-Trifluoromethyl-2-methyl-7-aminoquinoline (4b) ³²

Brown solid (0.18 g, 40% yield); mp 174-176 ºC; ¹H NMR (CDCl₃) δ 7.87 (dq, 1H, J₁ 2, J₂ 9 Hz, H-5),7.30 (s, 1H, H-3), 7.21 (d, 1H, J 2 Hz, H-8), 7.02 (dd, 1H, J₁ 2, J₂ 9 Hz, H-6), 4.18 (s, 2H, NH), 2.72 (s, 3H, CH₃); ¹³C NMR (DMSO-d₆) δ 158.1 (C-2), 150.7 (C-8a), 150.6 (C-7), 132.2 (q, ²J 30 Hz, C-4), 123.6 (C-5), 119.5 (C-6),118.3 (q, ¹J 275 Hz, CF₃), 113.5 (q, ³J 5 Hz, C-3), 112.2 (C-4a), 106.8 (C-8), 24.7 (CH₃); ¹⁹F NMR (376 MHz, CDCl₃) δ -61.25 (CF₃-4); GC-MS (EI, 70 eV, m/z) 226 (M⁺, 100), 210 (7), 199 (31), 157 (8), 142 (7), 69 (6%); Anal. calcd. for C₁₁H₉F₃N₂ (226.07): C, 58.41; H, 4.01; N, 12.38%. Found: C, 58.04; H, 4.01; N, 12.01%.

4-Trifluoromethyl-2-phenyl-7-aminoquinoline (4c)

Brown solid (0.22 g, 38% yield); mp 139-141 ºC; ¹H NMR (DMSO-d₆) δ 8.25 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 7.95 (s, 1H, H-3), 7.79 (dq, 2H, J₁ 2, J₂ 8 Hz, H-5), 7.57-7.51 (m, 3H, Ph), 7.21 (d, 1H, J 2 Hz, H-6), 7.16 (s, 1H, H-8), 6.15 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 155.4 (C-2), 151.0 (C-8a), 150.9 (C-7), 138.1 (C-Ph), 130.7 (q, ²J 30 Hz, C-4), 129.6, 128.7, 127.0 (5 C-Ph), 123.8 (q, ¹J 275 Hz, CF₃),123.7 (C-5), 120.5 (C-6), 113.0 (C-4a), 110.0 (q, ³J 5 Hz, C-3), 107.3 (C-8); ¹⁹F NMR (CDCl₃) δ -61.28 (CF₃-4); GC-MS (EI, 70 eV, m/z) 288 (M⁺, 100), 273 (5), 219 (20), 203 (5%); Anal. calcd. for C₁₆H₁₁F₃N₂ (288.09): C, 66.66;H, 3.85; N, 9.72%. Found: C, 66.32; H, 3.75; N, 9.64%.

4-Trifluoromethyl-2-(4-methylphenyl)-7-aminoquinoline (4d)

Yellow brown (0.14 g, 24% yield); mp 156-158 ºC; ¹H NMR (CDCl₃) δ 8.03 (d, 2H, J 8 Hz, Ph), 7.91 (dq, 2H, J₁ 2, J₂ 9 Hz, H-5), 7.86 (s, 1H, H-3), 7.34 (d, 2H, J 2 Hz, Ph), 7.31 (s, 1H, H-8), 7.04 (dd, 1H, J₁ 2, J₂ 9 Hz, H-6), 4.16 (s, 2H, NH₂), 2.43 (s, 3H, 2 CH₃); ¹³C NMR (DMSO-d₆) δ 156.9 (C-2), 150.9 (C-8a), 148.2 (C-7), 139.8, 136.0 (2 C-Ph), 134.5 (q, ²J 31 Hz, C-4), 129.5, 127.2 (4 C-Ph),124.8 (C-5), 123.7 (q, ¹J 275 Hz, CF₃), 119.4 (C-6), 115.2 (C-4a), 112.1 (q, ³J 5 Hz, C-3), 110.0 (C-8), 21.2 (CH₃); GC-MS (EI, 70 eV, m/z) 302 (M⁺, 100), 233 (23), 69 (10%); Anal. calcd. for C₁₇H₁₃F₃N₂ (302.10):C, 67.54; H, 4.33; N,9.27%. Found: C, 67.14; H, 4.19; N, 8.90%.

4-Trifluoromethyl-2-(4-methoxylphenyl)-7-aminoquinoline (4e)

Brown solid (0.13 g, 20% yield); mp 173-175 ºC; ¹H NMR (CDCl₃) δ 8.22 (dd, 2H, J₁2, J₂ 8 Hz, Ph), 7.89 (s, 1H, H-3), 7.80 (dq, 1H, J₁ 2, J₂ 9 Hz, H-5), 7.21 (s, 1H, H-8), 7.18 (dd, 1H, J₁ 2, J₂ 9 Hz, H-6), 7.10 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 5.98 (s, 2H, NH₂), 3.85 (s, 3H, OCH₃); ¹³C NMR (DMSO-d₆) δ 160.5 (C-2), 154.9 (C-8a), 150.6 (C-7), 132.8 (q, ²J 31 Hz, C-4), 130.4, 128.2 (3 C-Ph), 123.6 (q, ¹J 275, CF₃), 123.4 (q, ⁴J 2 Hz, C-5), 119.7 (C-6), 113.9 (3 C-Ph),112.5 (4a), 109.6 (q, ³J 5 Hz, C-3), 107.5 (C-8), 54.9 (2 OCH₃); GC-MS (EI, 70 eV, m/z) 318 (M⁺, 100), 233 (5), 249 (29), 69 (12%); Anal. calcd. for C₁₇H₁₃F₃N₂O (318.10):64.15;H, 4.12; N, 8.80%. Found: C, 63.89; H, 3.98; N, 8.80%.

4-Trifluoromethyl-2-(4-fluorophenyl)-7-aminoquinoline (4f)

Yellow solid (0.27 g, 45% yield); mp 191-193 ºC; ¹H NMR (DMSO-d₆) δ 8.33-8.29 (m, 2H, Ph), 7.93 (s, 1H, H-3), 7.79 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.37-7.33 (m, 2H, Ph), 7.21 (d, 1H, J 2 Hz, H-6), 7.18 (s, 1H, H-8), 6.10 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 163.1 (d, ¹J 248 Hz, C-FPh), 154.3 (C-2), 150.8 (C-8a), 150.6 (C-7), 134.4 (d, ⁴J 3 Hz, C-FPh), 133.1 (q, ²J 31 Hz, C-4), 129.1 (d,³J 8 Hz, 2 C-FPh), 123.5 (q, ¹J 275 Hz, CF₃), 123.4 (C-5), 120.3 (C-6), 115.3 (d, ²J 22 Hz, 2 C-FPh), 112.8 (C-4a), 109.9 (q, ³J 5 Hz, C-3), 107.2 (C-8); GC-MS (EI, 70 eV, m/z) 306 (M⁺, 100), 237 (22), 142 (8), 69 (16%); Anal. calcd. for C₁₆H₁₀F₄N₂ (306.08): C, 62.75; H, 3.29; N, 9.15%. Found:C, 62.58; H, 3.14; N, 9.01%.

2-(4-Clorophenyl)-4-trifluoromethyl-7-aminoquinoline (4g)

Yellow solid (0.22 g, 35% yield); mp 178-180 ºC; ¹H NMR (CDCl₃) δ 8.09 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 7.93 (dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.83 (s, 1H, H-3), 7.50 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 7.33 (d, 1H, J 2 Hz, H-8), 7.07 (dd, 1H, J₁ 2, J₂ 9 Hz, H-6), 4.20 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 154.2 (C-2), 151.1 (C-8a), 150.7 (C-7), 136.8, 134.6 (2 C-Ph), 133.3 (q, ²J 31 Hz, C-4), 128.8, 128.7 (4 C-Ph),125.1 (C-5), 125.5 (q, ¹J 275 Hz, CF₃), 122.3 (C-6), 119.6 (C-4a), 110.0 (q, ³J 5 Hz, C-3), 107.1 (C-8); ¹⁹ F NMR (CDCl₃) δ -61.30 (CF₃-4); GC-MS (EI, 70 eV, m/z) 322 (M⁺, 100), 303 (4), 283 (4), 253 (4), 239 (16%); Anal. calcd. for C₁₆H₁₀ClF₃N₂(322.05): C, 59.55; H, 3.12; N, 8.68%.Found: C, 59.63; H, 3.07; N, 8.61%.

2-(4-Bromophenyl)-4-trifluoromethyl-7-aminoquinoline (4h)

Yellow solid (0.24 g, 33% yield); mp 177-179 ºC; ¹H NMR (CDCl₃) δ 8.03 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 7.93(dq, 1H, J₁ 2, J₂ 8 Hz, H-5), 7.83 (s, 1H, H-3), 7.65 (dd, 2H, J₁ 2, J₂ 8 Hz, Ph), 7.33 (d, 1H, J 2 Hz, H-8), 7.07 (dd, 1H, J₁ 2, J₂ 8 Hz, H-6), 4.20 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 154.1 (C-2), 150.9 (C-8a), 150.6 (C-7),137.1 (C-Ph), 133.2 (q, ²J 31 Hz, C-4), 131.4, 128.8,123.5 (5 C-Ph), 123.6 (q, ¹J 275 Hz, CF₃), 123.2 (C-5),120.6 (C-6), 113.0 (C-4a), 109.8 (q, ³J 5 Hz, C-3), 107.1 (C-8); GC-MS (EI, 70 eV, m/z) 366 (M⁺, 100), 347 (6), 297 (14), 280 (4), 69 (5%); Anal. calcd. for C₁₆H₁₀BrF₃N₂(366.00): C, 52.34; H, 2.75; N, 7.63%. Found: C, 52.40; H, 2.71; N, 7.58%.

4-Trifluoromethyl-2-(4-nitrophenyl)-7-aminoquinoline (4i)

Beige solid (0.14 g, 21% yield); mp 199-201 ºC; ¹H NMR (CDCl₃) δ 7.98 (d, 2H, J 8 Hz, Ph), 7.87 (d, 1H, J 8 Hz, H-5), 7.80 (s, 1H, H-3), 7.30 (d, 1H, J 2 Hz, H-8),7.00 (d, 1H, J 2 Hz, H-6), 6.79 (d, 2H, J 8 Hz, Ph), 5.34 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 153.3 (C-2), 151.4 (C-8a),150.8 (C-7), 148.1, 143.9 (2 C-Ph), 133.5 (q, ²J 31 Hz, C-4), 128.4, 123.9 (4 C-Ph), 123.8 (q, ¹J 275 Hz, CF₃),123.7 (C-5), 121.6 (C-6), 113.5 (C-4a), 110.7 (q, ³J 5 Hz, C-3), 107.0 (C-8); ¹⁹ F NMR (CDCl₃) δ -61.23 (CF₃-4); GC-MS (EI, 70 eV, m/z) 333 (M⁺, 100), 314 (7), 264 (18), 248 (5), 69 (5%); Anal. calcd. for C₁₆H₁₀F₃N₃O₂ (333.07):C, 57.66; H, 3.02; N, 12.61%. Found: C, 57.52; H, 2.87; N, 12.68%.

4-Trifluoromethyl-2-(2-furyl)-7-aminoquinoline (4j)

To a stirred mixture of H₃PO₄ (0.8 mL) and P₂O₅ (1.2 g) (PPA) at 90 ºC, 2j (2 mmol) was added. Using an 10 cm length glass adapter connecting the flask reaction and the condenser, the mixture was stirred at 90 ºC for 36 h. Then, to the dark residue in the reaction flask was added 20 g of crushed ice and ethyl acetate (20 mL). After stirring, the 7-aminoquinoline 4j was isolated when the aqueous phase was extracted with ethyl acetate (6 × 20 mL) combined with NaOH solution 40% (5 mL). The organic layer was washed with distilled water (3 × 15 mL) and dried over sodium sulfate. After filtration, the liquid phase was stirred and heated in the presence of activated charcoal, filtered again and the solvent removed under reduced pressure.

Yellow solid (0.40 g, 73% yield), mp 235-238 ºC; ¹H NMR (DMSO-d₆) δ 7.96 (d, 1H, J 1 Hz, furyl), 7.79 (s, 1H, H-3), 7.75 (d, 1H, J 2 Hz, H-5), 7.43 (d, 1H, J 3 Hz, furyl), 7.19 (dd, 1H, J₁ 2, J₂ 9 Hz, H-6), 7.11 (d, 1H, J 2 Hz, H-8), 6.75-6.72 (m, 1H, J 2 Hz, furyl), 6.20 (s, 2H, NH₂); ¹³C NMR (DMSO-d₆) δ 152.5 (C-2), 151.2 (C-8a), 150.7 (C-7), 147.7,145.0 (2 C-furyl), 133.0 (q, ²J 31 Hz, C-4), 123.9 (C-5), 123.6 (q, ¹J 275 Hz, CF₃), 120.3 (C-6), 112.7 (C-4a), 112.6, 110.9 (2 C-furyl), 108.8 (q, ³J 5 Hz, C-3), 106.8 (C-8); CG-MS (EI, 70 eV, m/z) 278 (M⁺, 100), 250 (11), 69 (4%); Anal. calcd. for C₁₄H₉F₃N₂O (278.07): C, 60.44; H, 3.26; N, 10,07%. Found:C, 60.48; H, 3.25; N, 10.01%.

Supplementary Information

NMR spectra are available free of charge at http://jbcs.sbq.org.br as PDF file.

Acknowledgements

The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for fellowships and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support (Proc. No. 303.296/2008-9).

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37. Riedel, D.; Feindt, A.; Pulst, M.; J. Prakt. Chem. 1995,337,34.

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

39. Keller, H.; Schlosser, M.; Tetrahedron 1996,52,4637.

40. Sloop, J. C.; Bumgardner, C. L.; Loehle, W. D.; J. Fluorine Chem. 2002,118,135.

41. Schlosser, M.; Keller, H.; Sumida, S.-I.; Yang, J.; Tetrahedron Lett. 1997,38,8523.

42. Marull, M.; Lefebvre, O.; Schlosser, M.; Eur. J. Org. Chem. 2004,54.

43. Bruker, APEX2 (version 2.1), COSMO (version 1.56), BIS (version 2.0.1.9), SAINT (version 7.3A) and SADABS (version 2004/1) and XPREP 9 (version 2005/4), Bruker AXS Inc., Madison, Wisconsin, USA, 2006.

44. Sheldrick, G. M.; SHELXS-97, Program for Crystal Structure Solution, University of Göttingen, Germany, 1997.

45. Sheldrick, G. M.; SHELXL-97, Program for Crystal Structure Refinement, University of Göttingen, Germany, 1997.

46. Coppens, P.; Leiserowitz, L.; Rabinovich, D.; Acta Crystallogr. 1965,18,1035.

47. Farrugia, L. J.; J. Appl. Crystallogr. 1997,30,565.

Submitted: November 17, 2010

Published online: March 31, 2011

Supplementary Information

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Publication Dates

• Publication in this collection
  04 Aug 2011
• Date of issue
  Aug 2011

History

• Received
  17 Nov 2010
• Accepted
  31 Mar 2011