Novel Synthesis of 3,4,4-Trisubstituted

Download PDF
0 downloads 0 Views 85KB Size Report
Comment
120 (30, [C7H6NO]+), 104 (24, [C7H6N]+). 2d. IR (KBr): 3000, 2900, 2850 (CH3 stretch), 1520 (stretch of p-disub- stituted aromatic ring), 1365 (CH3, CH bend), ...
Novel Synthesis of 3,4,4-Trisubstituted Thiadiazolines from 3,4-Diphenyl1,2,5-Thiadiazole 1,1-Dioxide. Competition with the Intra-Molecular ArylAryl Cyclization of 3,4-Diphenyl-1,2,5-Thiadiazole 1,1-Dioxide 3,4 -TrisubstiutedThiadiazolinesfrom3,4-Diphenyl-1,25-ThiadF. María iazole1, -Dioxide Rozas,a Oscar E. Piro,b Eduardo. E. Castellano,c María V. Mirífico,a,d Enrique J. Vasini*a a

Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Facultad de Ciencias Exactas, Departamento de Química, Universidad Nacional de La Plata, C.C. 16, Suc. 4, (1900) La Plata, Argentina Fax +54(221)4254642; E-mail: [email protected] b Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and IFLP (CONICET), C. C. 67, 1900 La Plata, Argentina c Instituto Física de São Carlos, Universidade de São Paulo, C.P. 369, 13560 São Carlos (SP), Brazil d Departamento de Ingeniería Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata , La Plata, Argentina Received 19 March 2002; revised 3 July 2002 Abstract: 3,4-Diphenyl-1,2,5-thiadiazole 1,1-dioxide (1) reacted, in the presence of anhydrous aluminum trichloride, with aromatic nucleophiles possessing electron donor substituent groups to give novel (2a–e, Figure 1) 3,4,4-trisubstituted 1,2,5-thiadiazoline 1,1dioxides in good yield. In the presence of aluminum trichloride, but without the addition of nucleophiles, a slower, but practically quantitative intramolecular cyclization reaction (Scholl reaction1) of 1 to phenanthro[9,10-c]-1,2,5-thiadiazole 1,1-dioxide (3), took place. Both reactions occur through the intermediation of a strong electrophile formed by 1 and aluminum trichloride. Spectral data and structure (through single-crystal X-ray diffraction, with the exception of 2c) were measured for all new compounds. Key words: Lewis acids , heterocycles, sulfoxides, Scholl reaction, electrophilic aromatic substitutions

We have reported2a–d the addition reaction of alcohol nucleophiles to 1,2,5-thiadiazole 1,1-dioxides to form 3,4,4trisubstituted thiadiazoline derivatives (2f, Figure 1) with a 4-alkoxy substituent. It is interesting to synthesize similar thiadiazolines with a carbon-bonded substituent in the same position because of their therapeutic and synthetic applications.3a–d The standard preparation methods3b,4a,b are inconvenient because of the unavailability of the unsymmetrical precursors. A recently proposed synthesis3d is based on the Grignard addition of carbon nucleophiles to the C=N double bond of thiadiazoles to form trisubstituted thiadiazolines. We report here a different synthetic route to trisubstituted thiadiazoline 1,1-dioxides. The approach involves the attack of activated aromatic substrates (anisole, toluene, phenol, N,N-dimethylaniline or pyrrole) by a strong electrophile formed by the reaction of AlCl3 with 1. The new compounds 2a–e (Figure 1) have been prepared by this method. We consider our synthetic method and that proposed by Pansare3d to be complementary. In effect, a type 2 (Figure 1) thiadiazoline, with R = phenyl was synthesized by the Grignard method,3d while the application of our method produced, as expected,1 mainly polymers of benSynthesis 2002, No. 16, Print: 14 11 2002. Art Id.1437-210X,E;2002,0,16,2399,2403,ftx,en;M01002SS.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0039-7881

Figure 1

zene. Conversely, the addition of phenol to give 2c, which we obtained with high yields would have been impossible by the direct application of the Grignard method. It is interesting to note that, despite the fact that 1 has two identical electrophilic carbon atoms, only one reacted, even in the presence of a great excess of the aromatic substrate (e.g. when anisole or toluene were also used as solvents for the reaction). A similar observation has been made for the above mentioned Grignard based synthesis,3d and for the addition of alkoxy groups.2a–d A rationale is offered below for this behavior. When no aromatic substrates were added to the mixture of anhydrous AlCl3 and 1, a slower, but practically quantitative intramolecular cyclization (Scholl reaction1) of 1 to phenanthro[9,10-c]-1,2,5-thiadiazole 1,1-dioxide (3), was observed.

Competition Between the Formation Reactions of 3 and 2a As already mentioned, the electrophile formed by the reaction of 1 with anhydrous AlCl3 underwent a slow intramolecular cyclization reaction to form 3, or a faster electrophilic substitution reaction to form 2a–e, if a suitable aromatic substrate was present. The competition between these reactions was observed experimentally: anhydrous AlCl3 (1.21mmol) was added

is a copy of the author's personal reprint l

2399

l This

PAPER

2400

PAPER

M. F. Rozas et al.

to 1 (0.13 mmol) in dichloromethane (30 mL). After 2 hours, 3 could not be detected by TLC. Anisole (1.14 mmoles) was added at that moment. The solution turned yellow immediately and shortly thereafter 2a was detected by TLC. The reaction was monitored by TLC until complete consumption of 1 had occured. The reaction mixture contained 2a, but 3 was not detected. The same initial system (AlCl3, 1, CH2Cl2) was allowed to react for ca. 24 h. After which, the formation of 3 (TLC) was observed. At that moment, anisole (1.14 mmol) was added. 2a formation started (TLC) and continued until complete (TLC) consumption of 1 (45 h). The amount of 3 initially formed did not change appreciably. A mixture of 3 and anisole could also be partially converted into 2a in the presence of AlCl3: anhydrous AlCl3 (1.53 mmol) was added to a solution of of 3 (0.13 mmol) in CH2Cl2 (30 mL). The initially bright red solution of 3 turned dark green, and a solid of the same color was formed. However, a TLC analysis of the solution showed only 3 after 24 hours at room temperature. Anisole (0.93 mmol) was added to the solution at that moment. The green solid dissolved. The solution turned slowly from dark green to orange, and from orange to colorless. The presence of 2a was detected by TLC 60 min after the addition of anisole. The concentration of 2a increased with time, while that of 3 decreased. However, 3 could be detected in the mixture even after several days, long after the reaction had apparently stopped. The influence of the solvent was tested using the intramolecular cyclization reaction of 1 to 3. Similar experiments were run using different solvents (MeCN, CH2Cl2, CHCl3 and CCl4). No reaction took place in the MeCN solvent, but the reaction proceeded in all other solvents, including CCl4, in which 1 and AlCl3 are practically insoluble. In fact, the reaction occurred even in the absence of solvent, although it was considerably slower in the thick slurry that formed in these conditions. CH2Cl2 solvent was found to be the most convenient choice owing to the high yield of 3 (> 90%) obtained. It was found that a relatively high AlCl3 to 1 molar ratio (R) was necessary to obtain a good yield of 2a–e or 3. In reactions using 20 mmolar solutions of 1 in anisole, in which R was 1.5, 3.3 and 10, the yields of 2a were 0, 90 and 64%, respectively. Similar experiments without anisole (solutions of 1 in CH2Cl2) gave 0%, 4% and 93% yield of 3, respectively. We used generally a molar ratio of 10, which provided an adequate compromise between reaction rates and yields.

strong proton donor, usually formulated as HAlCl4. HCl is almost unavoidably present when using AlCl3, being formed by the reaction of AlCl3 with the residual water in the reaction solvent, or with the humidity in the atmosphere, while transferring the solid to the reaction vessel. Thus the influence of HCl was best tested by removing it from the reaction mixture, as in the following experiments. Compound 1 (0.12 mmol) was added to anisole (30 mL) that contained AlCl3 (1.27 mmol). The formation of 2a started immediately and the reaction was complete in ca. 10 h. In a duplicate experiment, anhydrous, anisole-saturated N2 gas was slowly bubbled through the anisole solvent for 30 min before the addition of AlCl3 and 1, and maintained thereafter for 20 hours. No 2a (TLC) was observed during the first 2 h of reaction, and only a small amount was found after 20 h, at the end of N2 bubbling. It was also observed that, after AlCl3 addition, the N2 gas stream carried HCl from the reaction vessel to an outlet water-trap, as indicated by a decrease in the pH of the trap-water and the formation of a AgCl precipitate when tested with a AgNO3 solution. After mixing the reactants for 20 hours the gas stream was switched to anhydrous, anisole saturated, gaseous HCl. The amount of 2a started to increase immediately and the reaction completed in 72 h. Similar results were found when the intramolecular condensation reaction of 1 to 3 was tested by the same method. The necessary presence of HCl indicates that an ionic mechanism prevails over a radical–cationic one.6 It is also true that, in the case of 1, the electron withdrawing characteristics of the >SO2 substituent disfavor the formation of phenylic cation-radicals.1 It must be mentioned that the presence of a strong Lewis acid, such as AlCl3, was necessary for the intramolecular conversion of 1 to 3 or the electrophilic attack to reactive aromatic substrates. No reaction could be observed if AlCl3 was substituted by HCl or H2SO4 in the reaction mixture.

Proposed Mechanism The experimental results indicate a common intermediate for the formation of 2a–e, or 3, which can be considered a protonated molecule of 1. (solvent–AlCl3) + HCl 1 + H+ + AlCl4–

® AlCl

4

–

+

+ AlCl4– + solvent (1)

+ 1H+ (2)

Reaction mechanisms to give 3 or 2a–d from 1H+ are shown in Scheme 1.

The Influence of HCl It is known5 that many, but not all, of the reactions that occur in the presence of AlCl3, require also HCl to form a

Synthesis 2002, No. 16, 2399–2403

®H

ISSN 0039-7881

© Thieme Stuttgart · New York

PAPER

3,4,4-Trisubstituted Thiadiazolines from 3,4-Diphenyl-1,2,5-Thiadiazole 1,1-Dioxide

2401

ized considering the molecular structure of 18 and of related thiadiazolines:9 the phenyl rings in 1 are rotated out from the plane of the heterocycle by ca. 40o, thus restricting their resonance interaction with the C=N double bonds. In the 1H+ cation, the dihedral angle would probably decrease to allow a better dispersal of the positive charge, but this dispersal must be incomplete, favoring the localization of the charge on the carbon atom of the heterocycle. In contrast, for thiadiazolines similar to 2a–e (3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide and 4-ethoxy-5-methyl-3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide8), the substituents of the sp3 heterocyclic carbon atom of the thiadiazolines are far from the region where they can hinder the phenyl group on the remaining sp2 carbon atom of the heterocycle from becoming practically coplanar with the heterocycle (dihedral angles are 7.6° and 10.7o respectively). The remaining sp2 carbon atom must be thus substantially less electrophilic than any of the heterocyclic carbon atoms of 1. Materials from the following sources were used. Anisole, toluene, N,N-dimethylaniline, CH2Cl2, phenol and pyrrole: commercial p.a. grade, purified by standard methods.10 AlCl3: Fluka. Compounds 1 and 3 were synthesized according to reported methods: 1,11 3.12 The reactions were carried out at r.t. (ca. 20 °C) and a catalyst to substrate molar ratio, R = [AlCl3]: [1], of ca. 10 was used, unless otherwise indicated. TLC analysis was routinely used to follow the course of the reactions (a reaction mixture sample of ca. 0.3 mL volume was dropped on a similar water volume. The organic phase was used for the analysis).

Scheme 1

It must be mentioned that we have recently obtained the reduced intermediate 3H2, by both chemical and electrochemical reduction of 3.7 The compound oxidizes easily in solution to 3, but can be obtained as a white solid by solvent evaporation in a reducing environment. The oxidation reaction of 3H2 to 3 (last reaction in Scheme 1) is therefore likely in the work-up of the reaction slurry. The postulation of a mechanism for the (partial) formation of 2a from 3 and anisole in the presence of AlCl3 requires further study, including the characterization of the green solid formed. The first step of the reactions of 1H+ in Scheme 1 can be described as an aromatic electrophilic substitution, the electrophile being the 1H+ cation. In the case of the formation of 3, the attacked site is the o-position of a phenyl ring deactivated by the strong electron withdrawing effect of the thiadiazole 1,1-dioxide group, while for the formation of type-2 thiadiazolines, the attack takes place at p-position on the activated nucleophilic ring. It is reasonable that, as experimentally observed, the intermolecular reaction be faster that the intramolecular cyclization. The increase in delocalization energy must be the driving force for the formation of 3. As above mentioned, only one of the two identical electrophilic carbon atoms of 1 reacted. This relative lack of reactivity, which was also observed in reactions with Grignard reagents3d and with alcohols,2a–d can be rational-

2a–e 2a,b Solid, anhyd AlCl3 was added to a 10–20 mM solution of 1 in anisole or toluene. 2c,d Solid, anhyd AlCl3 was added to a ca. 20 mM solution of 1 in CH2Cl2. The solvent was used to decrease the proportion of sideproducts in the case of 2d, and to dissolve solid phenol in the case of 2c. The nucleophile was added thereafter to a ca. 0.3 M initial concentration. 2e The procedure was similar to that used in the 2c–d cases, but the following changes were made: the system was protected from the light, a smaller catalyst ratio was used (R = 6), the nucleophile (0.1 M) was slowly added dropwise, and the reaction temperature was 0 °C. In general, the solutions darkened gradually during the course of the reaction, from an initial light yellow to a deep red–brown. In the cases of 2c–e, the CH2Cl2 solutions containing 1 and AlCl3 were initially light yellow, but changed to orange in a matter of minutes. Further darkening to a deep brown occurred after the addition of the nucleophile. The end of the reaction was judged by the disappearance of the TLC spot of 1. The reaction time was 1–5 h, but was much longer (ca. 30 h), in the case of 2d. Separation and Purification of Products Except in the case of 2d, the reaction mixture was poured into water, the organic phase was separated and washed with water to negative Al3+ reaction (alizarine). The organic phase was treated as follows.

Synthesis 2002, No. 16, 2399–2403

ISSN 0039-7881

© Thieme Stuttgart · New York

2402

PAPER

M. F. Rozas et al.

2a–b The organic phase was steam distilled. The remaining white solid was filtered and washed with Et2O. Crude yields were 65 and 92% for 2a and 2b, respectively. Purified crystals were obtained by recrystallization from benzene. Mp 179.5–180.0 °C (2a); mp 204– 205 °C (2b). 2c The organic phase was extracted with aq NaOH (8%). The aq solution was acidified (pH 1) with aq HCl (10%), and steam distilled to eliminate excess phenol. On cooling the distillation residue, a white solid was obtained. The solid was filtered, washed with Et2O and dried. A chromatographically (TLC) pure solid was obtained [yield: 90%, mp 231.5–232.0 °C (decomp.)]. 2d The reaction mixture was poured on water, made alkaline with NaOH to pH ca. 8. The organic phase was washed with H2O and steam distilled to eliminate excess solvent and N,N-dimethylaniline. The low-pressure evaporation of the distillation residue produced a solid. Crude 2d (38% yield) was obtained from the evaporation of the initial fractions of a flash chromatographic separation of the solid (60 mesh silica-gel filled column; CHCl3–CCl4, 10:1). Chromatographically pure pale-yellow crystals (mp 233.0–234.0 °C) were obtained by recrystallyzation of the crude product from CHCl3. 2e The organic phase was passed through a short column filled with activated charcoal and the solvent was evaporated. The solid obtained was placed on a flash chromatographic column [60 mesh silica-gel; eluted using successively CHCl3, CHCl3–EtOAc (1:4), EtOAc and EtOH]. Crude 2e (8% yield) was obtained from the evaporation of the CHCl3–EtOAc (1:4) fraction. Pure crystals were obtained from the slow evaporation of an ethanolic solution of the crude solid. All manipulations were performed under protection from light. Spectroscopic Measurements and Data 1 H and 13C NMR spectra were obtained with a 200 MHz instrument. All IR spectra (KBr pellets) presented the characteristic absorptions of 3,4-diphenyl-1,2,5-thiadiazolines 1,1-dioxide.2d The molecular ion could only be observed in the mass spectra of 2d. As it was the case for other thiadiazolines,3d fragmentation usually occurred at the C3–C4 and the N–S bonds of the heterocycle. Typical aromatic fragments were observed 2a IR (KBr): 2950, 2825 (CH3 stretch), 1510 (stretch of p-disubstituted aromatic ring), 1430 and 1360 (CH3, CH bend), 1260 and 1025 (CArOCAliph asymmetric and symmetric stretch, respectively), 820 (2 adj. H wag in p-disubstituted phenyl) cm–1.

MS: m/z (%) = 195 (41, [C14H13N]+), 194 (42, [C14H12N]+), 180 (100, [C13H10N]+), 167 (1, [C7H5NO2S]+), 118 (28, [C8H8N]+), 104 (21, [C4H6N]+). 2c IR (KBr): 3400 (OH stretch), 1510 (stretch of p-disubstituted aromatic ring), 820 (2 adj. H wag in p-disubstituted phenyl) cm–1. H NMR (DMSO-d6): d = 9.86 (s, 1 H), 9.36 (s, 1H), 7.64–6.78 (m, 14 H). 1

C NMR (DMSO-d6): d = 178.3, 157.7, 138.8–128.4 (10 signals), 115.5, 80.0. 13

MS: m/z (%) = 208 (1, [C14H10NO]+), 197 (70, [C13H11NO]+), 196 (100, [C13H10NO]+), 180 (40, [C13H10N]+), 167 (4, [C7H5NO2S]+), 120 (30, [C7H6NO]+), 104 (24, [C7H6N]+). 2d IR (KBr): 3000, 2900, 2850 (CH3 stretch), 1520 (stretch of p-disubstituted aromatic ring), 1365 (CH3, CH bend), 1230 (CArN stretch), 820 (2 adj. H wag in p-disubstituted phenyl) cm–1. H NMR (DMSO-d6): d = 9.23 (s, 0.3 H), 7.67–6.73 (m, 14 H), 2.90 (s, 6 H). 1

C NMR (DMSO-d6): d = 178.3, 150.0, 138.9–124.5 (9 signals), 111.8, 80.0.

13

MS: m/z (%) = 391 (5, M+), 224 (100, [C15H16N2]+), 180 (39, [C13H10N]+), 167 (1, [C7H5NO2S]+), 147 (14, [C9H11N2]+), 104 (18, [C7H6N]+). 2e IR (KBr): 3450 (NH stretch) cm–1. H NMR (DMSO-d6): d = 10.73 (s, 1 H), 7.63–7.25 (m, 10 H), 6.77 (s, 1 H), 5.97 (s, 1 H), 5.69 (s, 1 H). 1

C NMR (DMSO-d6): d = 176.8, 141.1, 132.7–127.5 (8 signals), 118.8, 108.8, 107.6, 77.5.

13

X-ray Analysis Single crystal X-ray data were obtained with Enraf-Nonius CAD-4 diffractometers, using the w-2J scan technique and graphite monocromated CuKa radiation (l = 0.54184 Å) for compounds 2b and 2d, in the J range from 3.93 to 69.90° (2b) and from 3.94 to 69.90° (2d), and MoKa radiation (l = 0.71073 Å) for compound 2a in the 2.06 < J < 27.97° range. Compound 2e was measured with a KappaCCD diffractometer using j and w scans and MoKa radiation in the J range from 2.11 to 27.51°. An ORTEP diagram of 2a is presented in Figure 2 as an example of the structure of the compounds. Detailed X-ray structural data are available on request for all compounds except 2c.

H NMR (DMSO-d6): d = 7.0–7.7 (m, 14 H), 3.75 (s, 3 H).

1

C NMR (DMSO-d6): d = 178.0, 159.2, 138.6–128.2 (10 signals), 114.0, 55.1. 13

MS: m/z (%) = 211 (99.6, [C14H13NO]+), 210 (100, [C14H12NO]+), 180 (91, [C13H10N]+), 167 (13, [C7H5NO2S]+), 134 (35, [C8H8NO]+), 104 (22, [C7H6N]+). 2b IR (KBr): 3000, 2900 (CH3 stretch), 1510 (stretch of p-disubstituted aromatic ring), 1360 (CH3, CH bend) cm–1. 1 H NMR (DMSO-d6): d = 9.46 (s, 1 H), 7.65–7.23 (m, 14 H), 2,29 (s, 3 H).

C NMR (DMSO-d6): d = 177.8, 138.3–128.2 (11 signals), 79.9, 20.3.

13

Synthesis 2002, No. 16, 2399–2403

ISSN 0039-7881

Figure 2

© Thieme Stuttgart · New York

PAPER

3,4,4-Trisubstituted Thiadiazolines from 3,4-Diphenyl-1,2,5-Thiadiazole 1,1-Dioxide

Crystallographic Data The single crystals were obtained by slow evaporation of the solvent from MeCN (2a) or EtOH (2b,d,e) solutions of the compounds. The structures were solved by direct and Fourier methods and the final molecular model obtained by full-matrix least-squares refinement on F2, employing the SHELXS-97 and SHELXL-97 programs. All hydrogen atoms except the amine ones of compound 2e were found in difference Fourier maps. However, the H-atoms of the phenyl rings in all compounds and the ones belonging to the pyrrole group of 2e were positioned stereochemically and refined with the riding model. The methyl hydrogen atoms in compounds 2a,b,d were treated in the refinement as rigid bodies and allowed to rotate around the corresponding C–C (2b), C–O (2a) or C–N (2d) bond such as to maximize the sum of the observed electron density at the three calculated H-positions. As expected, all methyl groups converged to staggered conformations. The amide H-atom of the heterocycle in compounds 2a–c was refined isotropically starting from the found location. In the case of compound 2a, N–H bond distance was restrained to a target value of 0.86(1) Å. 2a C21H18N2O3S, M = 378.43, crystal dimensions 0.4 ´ 0.4 ´ 0.2 mm, triclinic, P–1, a = 9.808(1) Å, b = 9.932(2) Å, c = 10.004(2) Å, a = 88.80(2)°, b = 66.65(1)°, g = 83.51(1)°, V = 888.7(3) Å3, Z = 2, rcalcd = 1.414 g×cm–3, 4524 reflections measured, 4283 independent, R1 = 0.060 [1637 reflections with I > 2s(I)], wR2 = 0.103, 244 parameters, with non-H atoms refined anisotropically, residual electron density 0.306/–0.396 e×Å–3. 2b C21H18N2O2S, M = 362.43, crystal dimensions 0.4 ´ 0.3 ´ 0.2 mm, triclinic, P–1, a = 10.234(1) Å, b = 10.8410(7) Å, c = 10.003(2) Å, a = 124.52(1)°, b = 92.83(1)°, g = 93.93(1)°, V = 906.9(2) Å3, Z = 2, rcalcd = 1.327 g×cm–3, 3607 reflections measured, 3415 independent, R1 = 0.040 [3308 reflections with I > 2s(I)], wR2 = 0.112, 241 parameters, with non-H atoms refined anisotropically, residual electron density 0.26/–0.28 e×Å–3. 2d C22H21N3O2S, M = 391.48, crystal dimensions 0.36 ´ 0.27 ´ 0.11 mm, triclinic, P1, a = 9.767(3) Å, b = 10.182(4) Å, c = 11.513(2) Å, a = 80.44(2)°, b = 78.11(2)°, g = 62.17(3)°, V = 987.5(5) Å3, Z = 2, rcalcd = 1.317 g×cm–3, 6362 reflections measured, 3740 independent, R1 = 0.041 [3514 reflections with I > 2s(I)], wR2 = 0.116, 260 parameters, with non-H atoms refined anisotropically, residual electron density 0.29/–0.34 e×Å–3. 2e C36H30N6O4S, M = 674.81, crystal dimensions 0.2 ´ 0.2 ´ 0.15 mm, monoclinic, Cc, a = 13.8442(4) Å, b = 13.8026(6) Å, c = 17.5639(8) Å, b = 103.860(3)°, V = 3258.5(2) Å3, Z = 4, rcalcd = 1.375 g×cm–3, 13400 reflections measured, 6639 independent, R1 = 0.052 [6639 reflections with I > 2s(I)], wR2 = 0.156,

2403

434 parameters, with non-H atoms refined anisotropically, residual electron density 0.27/–0.39 e×Å–3.

Acknowledgment This work was financially supported by the Universidad Nacional de La Plata (UNLP), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC Pcia. de Bs. As.), and by the Fundação de Amparo a Pesquisa de Estado do São Paulo (FAPESP), and the Fundação Vitae of Brazil, M.F.R. is research a professional from CONICET and UNLP, M.V.M. is a researcher from CONICET and UNLP, E.J.V. is a researcher from CICPcia. de Bs. As and UNLP, O.E.P. is a researcher from CONICET and UNLP, and E.E.C. is a researcher from Instituto Fisica de São Carlos, Universidade de São Paulo, Brazil.

References (1) Kovacic, P.; Jones, M. B. Chem. Rev. 1987, 87, 357. (2) (a) Mirífico, M. V.; Vasini, E. J.; Sicre, J. E. J. Phys. Org. Chem. 1993, 6, 341. (b) Mirífico, M. V.; Vasini, E. J. Anales de Química 1995, 91, 557. (c) Caram, J. A.; Mirífico, M. V.; Aimone, S. L.; Vasini, E. J. Can. J. Chem. 1996, 74, 1564. (d) Aimone, S. L.; Caram, J. A.; Mirífico, M. V.; Vasini, E. J. J. Phys. Org. Chem. 2000, 13, 272. (3) (a) Sartor, D.; Saffrich, J.; Helmchen, G.; Richards, C. J.; Lambert, H. Tetrahedron: Asymmetry 1991, 2, 639. (b) Ahn, K. H.; Yoo, D. J.; Kim, J. S. Tetrahedron Lett. 1992, 33, 6661. (c) Castro, J. L.; Matassa, V. G. J. Org. Chem. 1994, 59, 2289. (d) Pansare, S. V.; Rai, A. N.; Kate, S. N. Synlett 1998, 623. (4) (a) McDermott, S. D.; Spillane, W. J. Org. Prep. Proced. Int. 1984, 16, 49. (b) Baker, R. J.; Chiu, S. K.; Klein, C.; Timberlake, J. W.; Trefonas, L. M. J. Org. Chem. 1980, 45, 482. (5) Thomas, C. A. Anhydrous Aluminum Chloride in Organic Chemistry, Am. Chem. Soc. Monograph Series No. 87; Reinhold Publishing: N.Y., 1941. (6) Clowes, G. A. J. Chem. Soc. (C) 1968, 2519. (7) Svartman, E. L.; Caram, J. A.; Mirífico, M. V.; Vasini, E. J. Can. J. Chem. 1999, 77, 511. (8) Castellano, E. E.; Piro, O. E.; Caram, J. A.; Mirífico, M. V.; Aimone, S. L.; Vasini, E. J.; Glossman, M. D. J. Phys. Org. Chem. 1998, 11, 91. (9) Castellano, E. E.; Piro, O. E.; Caram, J. A.; Aimone, S. L.; Mirífico, M. V.; Vasini, E. J.; Marquez-Lucero, A.; Glossman-Mitnik, D. J. Mol. Struct. 2001, 597, 163. (10) (a) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd. ed.; Pergamon Press: Oxford, 1989. (b) Riddick, J. A.; Bunger, W. B. In Techniques of Chemistry, Vol. II; Weissberger, A., Ed.; WileyInterscience: N.Y., 1970. (11) Wright, J. B. J. Org. Chem. 1964, 29, 1905. (12) Vorriether, H. K.; Ziegler, E. Monatsh. Chem. 1965, 96, 216.

Synthesis 2002, No. 16, 2399–2403

ISSN 0039-7881

© Thieme Stuttgart · New York