Article

J. Mex. Chem. Soc. 2005, 49(3), 302-306 2005, Sociedad Qumica de Mxico ISSN 1870-249X
Eco-friendly Conditions for the Production of 1,3-Dithianes Using Microwave Irradiation
Lidia Ballesteros,1 Olivia Noguez,1 Gabriel Arroyo,1 Benjamn Velasco,1 Francisco Delgado,2 and Ren Miranda*1
Departamento de Ciencias Qumicas, Facultad de Estudios Superiores Cuautitln, Universidad Nacional Autnoma de Mxico. Av. Primero de Mayo s/n, Cuautitln Izcalli C.P. 54740, Estado de Mxico, Mxico. Tel/fax 5 6232056, e-mail mirruv@yahoo.com.mx 2 Departamento de Qumica Orgnica, Escuela Nacional de Ciencias Biolgicas, Instituto Politcnico Nacional, Prolongacin Carpio y Plan de Ayala, Casco de Santo Toms, Mxico D.F., C.P. 04510, Mxico. Recibido el 31 de mayo del 2005; aceptado el 30 de septiembre del 2006
Abstract. The reaction of a number of aldehydes and ketones with 1,3-propanedithiol has been carried out in the absence of solvent, using microwave irradiation as the heat source. Under these conditions the corresponding 1,3-dithianes were obtained in short reaction times (5 min). In addition, a bentonitic clay was evaluated as promoter of this reaction. Key words: Green chemistry; 1,3-dithianes; bentonitic clay; microwave irradiation. Resumen. La reaccin entre varios aldehdos y cetonas con 1,3propanditiol se llevo a cabo en la ausencia de disolvente, utilizando irradiacin de microondas como fuente de calor. Bajo estas condiciones, se obtuvieron los correspondientes 1,3-ditianos, en tiempos cortos de reaccin (5 min). Complementariamente, se evalu la capacidad de una arcilla bentonitca como promotora de esta reaccin. Palabras clave: Qumica verde; 1,3-ditianos; arcilla bentontica; radiacin de microondas.

Introduction

An objective of green chemistry is to carry out reactions under conditions which are not detrimental to the environment [1], and the ideal synthesis is that, in which the target molecule is produced quantitatively in one step, from available and inexpensive starting compounds, in an environmentally acceptable process [2]. The high stability of dithioacetals and consequently the specific conditions required for their removal from masked carbonyls have afforded priceless uses of them in synthesis [3]. In addition, there are several reasons why cyclic dithioacetals in general, and 1,3-dithianes in particular, attracted the attention of synthetic chemists [4]. For example, these compounds are easily metallated with alkyllithium solutions, and the resulting carbanions can be employed as effective nucleophiles in C-C bond-forming reactions; additionally, they play an important role in the synthon and umpolung concepts [5,6], and some 1,3-dithianes have been objects of study for the anomeric effect [7,8]. After an extensive search of the literature, it was encountered that, the standard procedure for the preparation of 1,3dithianes consists in the Lewis or Brnsted acid-catalyzed transformation of carbonylic substrates or their corresponding O,O-acetals with 1,3-propanedithiol [9]. Also, the reaction of 1,3-propanedithiol with gem-diiodo alkanes affords the access to 1,3-dithiacyclohexanes [10]. The most common catalysts employed to produce 1,3-dithianes are: HCl, HCl/ZnCl 2 [11,12], BF 3. Et 2 O [12-14], p-toluenesulfonic acid [15], HCOOH [16], UF 6[10], SnCl2[17], and bis(diphenylphosphine)methane complexes of platinum (II) [18]. The literature
also informs on the use of undesirable solvents such as CHCl3, C 6H 6, THF, HCOOH, 1,2-trichlorotrifluorometane (Freon 113), CH2Cl2, C7H8 and Me2CO, (vide supra). Recently, for the production of a wide number of S,Sacetals, the employment of two eco friendly-clays KSF [19] and TAFF [20, 21] has been reported; however, these methods make use of very toxic solvents such as benzene or toluene. It is also worth noting that microwave irradiation and solventless conditions have been employed to produce cyclic S,Sacetals [22-24], however, these procedures involve exchange reactions from other masked carbonylic compounds, as well as the presence of an acid as catalyst. The aim of this work is to inform on the one-pot production of two series of 1,3-dithianes, 3a-i and 5j-m, under solventless conditions, using microwave irradiation as the heat source. In addition TAFF, an eco-friendly bentonitic clay [21] was evaluated as catalyst.

Results and Discussion

The reactions performed in this work are shown in Scheme 1, and the corresponding results are summarized in Table 1. As it can be seen, the reaction of aldehydes (1a-i) or ketones (4j-m) with 1,3-propanedithiol (2), under solventless conditions and using microwave irradiation as the energy source, gives 1,3dithianes 3a-i and 5j-m in good yields, and in very short times. In addition, the comparative study, in which TAFF, an eco-friendly bentonitic clay was evaluated as catalyst (Table 1), demonstrated that an acidic promotor [21] is not required for the production of the target molecules. Moreover, it is
Eco-friendly Conditions for the Production of 1,3-Dithianes Using Microwave Irradiation Table 1. Microwave production of 1,3-dithianes 3a-i and 5j-m Product With TAFF Yielda (Formation)b 92 (100) 89 (97) 80 (99) 88 (95) 86 (96) 89 (99) 93 (100) 87 (97) 84 (94) c (3.8) 24 (36) 77 (98) c (12)
workup. bDetermined by GCMS. cNot determinated.
Without TAFF Yielda (Formation)b 89 (97) 81 (90) 78 (91) 89 (91) 60 (91) 84 (99) 89 (97) 81 (88) 78 (91) c (3.2) 27 (39) 69 (95) c (12)
3a 3b 3c 3d 3e 3f 3g 3h 3i 5j 5k 5l 5m

a After

[M-43]+, [M-65]+, [M-74] + and [M-75]+. In general, the corresponding proton nuclear magnetic resonance data of the molecules gave evidence for the presence of the 1,3-dithiane moieties, since the S,S-cyclic acetals showed analogous chemical shifts and coupling patterns: dtt 1.81-1.98 ppm Ha-5, dtt 2.10-2.21 ppm He-5, ddd 2.85-2.97 Ha-4,6, and ddd 2.90-3.18 He-4,6 with coupling constants of J4a/4e ~ J5a/5e ~ 13-14 Hz; J4a/5a = 10-12 Hz; J4a/5e ~ J4e/5a = 2.6-3.4 Hz; J4e,5e=4-6 Hz; this in addition to the corresponding shifts and patterns of the protons in the substituents at C-2. Finally, it is important to note that the dithianes 5j and 5m were produced in low quantities due to steric factors; consequently they were only identified by GCMS.

Experimental

General features: All aldehydes and ketones are commercially available (Aldrich Chemical Co.) and were employed without further purification. Camphorquinone was prepared by a previously reported procedure [25]. The TAFF, a bentonitic clay, was obtained from Tonsil Mexicana S.A de C.V., Insurgentes Sur, C.P. 01020 Mexico-City [26]. The reactions were monitored by TLC (n-hexane/AcOEt, 4:1) on precoated (0.25 mm) Merk silica-gel 60-F254 aluminum sheets; the visualization of the products was done using a 254 nm UV lamp (UVP Mod UVLS-24); for the corresponding column chromatographies (flash) silica gel Merck 230-400 mesh was employed. The melting points were determined in a Fisher Scientific apparatus, and are uncorrected. The refraction index was determined

worth noting that the use of microwave irradiation has been previously evaluated [22-24] for the same purpose, however, a protected carbonylic moiety and an acid-catalyst were employed; consequently, this new procedure is a complete green chemistry protocole. For the identification of compounds 3a-i and 5j-m, firstly, we envisaged by mass spectrometry [20] the presence of the molecular radical ions in agreement with the corresponding molecular weights, this in addition to analogous fragments that follow a typical fragmentation pattern for a 1,3-dithiane:

Scheme 1

J. Mex. Chem. Soc. 2005, 49(3)
Lidia Ballesteros, et al.
in an Abbe Refractometer Bausch & lamb serial No. U321141R, boiling points were determined by the Siwoloff method. The products were identified by mass spectrometry; EIMS (70 ev) spectra by direct introduction (pure compounds) were obtained using a Finnigan Mat-GCQ. The corresponding conversion percentages, were determined by GC-MS employing a Varian Saturn 4D under EI mode, equipped with a capillary column 30 m length by 0.25 mm diameter, packed with 5% phenyl and 96% dimethylpolysiloxane. The complement identification of the products was performed by 1H NRM in a Varian Mercury XR-300 Spectrometer using CDCl 3 or DMSO-d6 as the solvent and tetramethylsilane as internal reference. General procedure.- A mixture of aldehyde 1a-i or ketone 4j-m (2 mmol) and 1,3-propanedithiol 2 (2 mmol) was placed in a reactor with a diameter of 4.4 cm, where upon it was treated during 5 min with microwave irradiation (600W) in a conventional microwave oven (Samsung, Mod. MW1040WA). Analogous experiments were performed, for comparison, in the presence of TAFF as catalytic promoter (250 mg). 2-Phenyl-1,3-dithiane (3a). White solid: mp 68-69 C; 1H NMR (CDCl3, 300 MHz) 1.95 (1H, dtt, H-5a), 2.20 (1H, dtt, H-5e), 2.90 (2H, ddd, H-4a,6a), 3.06 (2H, ddd, H-4e,6e), 5.17 (1H, s, H-2), 7.35 (5H, m, H-Ar); 13C NMR (CDCl3, 75 MHz) 25.05 (C-5), 32.05 (C-4,6), 51.42 (C-2), 127.69 (C-2, 6), 128.39 (C-3,5), 128.67 (C-4), 139.02 (C-1); EIMS m/z (rel. int.): 196 [M](100), 153 (7.5), 149 (3.4), 135 (7.5), 131 (21.2), 122 (21),121 (55), 117 (5), 105 (12.8), 74 (7). Yield: 89%. 2-(3-Bromophenyl)-1,3-dithiane (3b).Yellow oil: bp 132 C, nD25 1.560; 1H NMR (CDCl3, 300 MHz) 1.91 (1H, dtt, H5a), 2.19 (1H, dtt, H-5e), 2.93 (2H, ddd, H-4a,6a), 3.05 (2H, ddd, H-4e, 6e), 5.11 (1H, s, H-2), 7.20 (2H, m, H-56), 7.41 (2H, m, H-24); 13C NMR (CDCl3, 75 MHz) 24.89 (C-5), 31.87 (C-4,6), 50.53 (C-2), 126.73 (C-5), 130.52 (C-6), 131.20 (C-4), 131.80 (C-2), 141.45 (C-1), 142.67 (C-3); EIMS m/z (rel. int.): 276 (97.4), 274 (100) [M], 226 (1.5), 200 (37), 199 (9.5), 105 (47), 74 (33.5). Yield: 81%. 2-(2-Chlorophenyl)-1,3-dithiane (3c). White solid: mp 90-92 C; 1H NMR (CDCl3, 300 MHz) 1.91 (1H, dtt, H-5a), 2.20 (1H, dtt, H-5e), 2.89 (2H, ddd, H-4a,6a), 3.11 (2H, ddd, H4e,6e), 5.64 (1H, s, H-2), 7.21 (1H, ddd, J5,3= 1.8, J5,4=J5,6 7.2 Hz, H-5), 7.30 (1H, ddd, J4,6= 1.5, J4,3=J4,5 7.2 Hz, H4), 7.36 (1H, dd, J6,4= 1.5, J6,5= 7.2 Hz, H-6), 7.68 (1H, ddd, J3,4= 7.2, J3,5= 1.8 Hz, H-3); 13C NMR (CDCl3, 75 MHz) 25.10 (C-5), 32.23 (C-4,6), 47.56 (C-2), 127.44 (C-5), 129.44 (C-6), 129.59 (C-4), 129.62 (C-3), 132.40 (C-2), 136.50 (C-1); EIMS m/z (rel. int.): 232 (32), 230 (100) [M], 165 (2.5), 156 (5.5), 155 (17), 105 (5.5), 74 (3). Yield: 78%. 2-(4-Cyanophenyl)-1,3-dithiane (3d). White solid: mp 108110 C; 1H NMR (CDCl3, 300 MHz) 1.98 (1H, dtt, H-5a), 2.20 (1H, dtt, H-5e), 2.92 (2H, ddd, H-4a,6a), 3.05 (2H, ddd,

H-4e,6e), 5.18 (1H, s, H-2), 7.61 (4H, AABB, J= 6.6 Hz, H2,3,5,6); 13C NMR (CDCl3, 75 MHz) 24.75 (C-5), 31.69 (C-4,6), 50.62 (C-2), 112.11 (C-1), 118.41 (C-2,6), 128.63 (C-3,5), 132.49 (C-4), 144.13 (C-7); EIMS m/z (rel. int.): 221 (100) [M], 178 (12.5), 160 (6.5), 156 (8.6),147 (20.1), 146 (60.5), 142 (1.5), 105 (21.2), 74 (52.1). Yield: 89%. 2-(4-Formylphenyl)-1,3-dithiane (3e). White solid: mp 8688 C; 1H NMR (Me2CO-d6, 300 MHz) 1.85 (1H, dtt, H-5a), 2.21 (1H, dtt, H-5e), 2.97 (2H, ddd, H-4a,6a), 3.18 (2H, ddd, H-4e,6e), 5.47 (1H, s, H-2), 7.81 (4H, AABB, J= 8.4 Hz, H2,3,5,6), 10.04 (1H, s, H-7); 13C NMR (Me2CO-d6, 75 MHz) 25.92 (C-5), 32.19 (C-4,6), 51.29 (C-2), 129.42 (C2,6), 130.67 (C-3,5), 130.80 (C-4), 141.20 (C-1), 192.38 (C-7); EIMS m/z (rel. int.): 224 (100) [M], 181 (3.1), 177 (1), 159 (31.7), 150 (13.6), 149 (51), 105 (26), 74 (21). Yield: 60%. 2-(4-Fluorophenyl)-1,3-dithiane (3f). White solid: mp 96-98 C; 1H NMR (CDCl3, 300 MHz) 1.94 (1H, dtt, H-5a), 2.15 (1H, dtt, H-5e), 2.93 (2H, ddd, H-4a,6a), 3.05 (2H, ddd, H4e,6e), 5.15 (1H, s, H-2), 7.45 (4H, AABB, J= 5.1 Hz, H2,3,5,6); 13C NMR (CDCl3, 75 MHz) 24.94 (C-5), 32.10 (C-4,6), 50.47 (C-2), 115.60 (C-2,6), 129.50 (C-3,5), 135.00 (C-1), 160.90 (C-4); EIMS m/z (rel. int.): 214 (100) [M], 171 (5), 153 (4), 149 (10), 140 (4), 139 (15.7), 105 (13), 74 (4). Yield: 84%. 5-{(1,3-Dithian-2-yl)benzo[d]-1,3}dioxole (3g). White solid: mp 85-87 C; 1H NMR (CDCl3, 300 MHz) 1.98 (1H, dtt, H5a), 2.18 (1H, dtt, H-5e), 2.85 (2H, ddd, H-4a,6a), 3.05 (2H, ddd, H-4e,6e), 5.09 (1H, s, H-2), 5.95 (2H, s, H-2), 6.74 (1H, d, J7,6 = 8.5 Hz, H-7), 6.90 (1H, d, J4,6 = 1.5 Hz, H-4), 6.98 (1H, dd, J6,7 = 8.1, J6,4 1.5 Hz, H-6); 13C NMR (CDCl3, 75 MHz) 24.94 (C-5), 32.10 (C-4,6), 51.10 (C-2), 101.16 (C-2), 108.30 (C-4,7), 121.21 (C-6), 132.84 (C-1a,3a), 147.60 (C-5); EIMS m/z (rel. int.): 240 (62.1) [M], 197 (3.4), 193 (1), 179 (2.5), 175 (6.7), 166 (17.5), 165 (21), 161 (3.1), 105 (5), 74 (13.1). Yield: 89%. 2-(4-Hydroxyphenyl)-1,3-dithiane (3h). Brown solid: mp 146-148 C; 1H NMR (Me2CO-d6, 300 MHz) 1.81 (1H, dtt, H-5a), 2.13 (1H, dtt, H-5e), 2.86 (2H, ddd, H-4a,6a), 3.10 (2H, ddd, H-4e,6e), 5.24 (1H, s, H-2), 7.05 (4H, AABB, J = 8.7 Hz, H-2,3,5,6); 13C NMR (Me2CO-d6, 75 MHz) 26.00 (C-5), 32.54 (C-4,6), 51.17 (C-2), 116.50 (C-3,5), 129.82 (C-26), 131.71 (C-1),158.21 (C-4); EIMS m/z (rel. int.): 212 (78) [M], 169 (5.2), 165 (2), 151 (5.5), 147 (2), 137 (81), 105 (7.5), 74 (3). Yield: 81%. 2-(4-Methoxyphenyl)-1,3-dithiane (3i). Pink solid: mp 109111 C; 1H NMR (Me2CO-d6, 300 MHz) 1.81 (1H, dtt, H5a), 2.16 (1H, dtt, H-5e), 2.85 (2H, ddd, H-4a,6a), 3.11 (2H, ddd, H-4e, 6e), 3.79 (1H, s, H-7), 5.28 (1H, s, H-2), 7.14 (4H, AABB, J = 8.7 Hz, H-2,3,5,6); 13C NMR (Me2CO-d6, 75 MHz) 25.96 (C-5), 32.45 (C-4,6), 51.01 (C-7), 55.53 (C-2),

114.71 (C-3,5), 129.73 (C-2,6), 132.80 (C-1), 160.46 (C4); EIMS m/z (rel. int.): 226 (100) [M]; 183 (3), 179 (2), 165 (4.1), 161 (10.1),152 (29.9), 151 (63.4), 105 (17.5), 74 (18). Yield: 78%. Spiro [1,7,7-trimethyl- bicyclo[2.2.1]-heptan-3.2-1,3dithiane] (5j). EIMS m/z (rel. int.): 242 (88) [M], 199 (27), 195 (3), 181 (14), 168 (27), 167 (10), 163 (3), 105 (27), 74 (35). Formation (GC-EIMS): 3.2%. Spiro [1,7,7-trimethyl-2-oxo- bicyclo[2.2.1]heptan-3.21,3-dithiane] (5k). Colorless oil: bp 108 C, nD25 1.537; 1H NMR (CDCl3, 300 MHz) 0.92 (3H, s, Me-8), 0.94 (3H, s, Me-10), 1.0 (3H, s, Me-9), 1.25 (2H, m, H-5a,5e), 1.90 (2H, m, H-6a,6e), 1.91 (1H, dtt, H-5a), 2.21 (1H, dtt, H-5e), 2.28 (1H, m, H-4), 2.90 (2H, ddd, H-4a,6a), 3.05 (2H, ddd, H-4e, 6e); 13C NMR (CDCl , 75 MHz) 9.50 (C-10), 18.80 (C-8), 19.(C-9), 20.64 (C-5), 24.19 (C-5), 30.97 (C-6), 33.45 (C-4,6), 45.01 (C-7), 48.80 (C-4), 51.90 (C-3), 59.70 (C-1), 217.07 (C2); EIMS m/z (rel. int.): 256 (10) [M], 213 (1.5), 195 (17), 182 (3), 181 (19.5), 105 (8), 74 (1). Yield: 27% Spiro [cyclohexan-1.2-1,3-dithiane] (5l). Colorless oil: bp 68 C, D25 1.486; 1H NMR (Me2CO-d6, 300 MHz) 1.50 (6H, m, H-3,4,5), 1.84 (1H, dtt, H-5a), 1.91 (4H, m, H2,6), 2.10 (1H, dtt, H-5e), 2.68 (2H, ddd, H-4a,6a), 2.90 (2H, ddd, H-4e,6e); 13C NMR (Me2CO -d6, 75 MHz) 21.54 (C3,5), 25.5 (C-5), 25.7 (C-4), 32.90 (C-4,6), 37.42 (C-2,6), 49.82 (C-2); EIMS m/z (rel. int.): 188 (100) [M], 145 (19), 127 (3.5), 114 (9.5), 113 (7.5), 105 (5), 74 (2). Yield: 69%. Spiro [5-methyl-2-isopropyl- cyclohexan-1.2-1,3-dithiane] (5m). EIMS m/z (rel. int.): 244 (100) [M], 201 (10.5), 183 (2), 170 (5.5), 169 (33.5), 165 (9), 105 (7), 74 (6.5). Formation (GC-EIMS): 12%.
protection of carbonylic compounds, giving 1,3-dithianes, also we found that the presence of an acidic medium is irrelevant in this conditions. In addition no exchange of protecting group is occurred [23,24].

Acknowledgements

The authors thank DGAPA-UNAM for financial support, (grant number IN-208202).

References

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Conclusion

One of Fischers contributions to the progress of organic synthesis was the notion that a functional group could be temporarily masked by means of a suitable protecting group, which could then be later specifically removed. However, even after more than a century the masking of functional groups still remains an important challenge in organic synthesis; for example, the protection of an aldehyde or a ketone is frequently a necessary step in synthetic chemistry. In this sense, the dithiane system is a common way for the protection of carbonylic moieties; however, the published procedures for this purpose usually require conditions that are hazardous to the environment, such as toxic solvents and acids. In this paper we described a solventless procedure for the one-pot