You are on page 1of 4

PAPER

45

Trichloroisocyanuric Acid as a Cohalogenating Reagent: An Efficient Transformation of Alkenes into Chlorohydrins, b-Chloroethers and b-Chloroacetates
TGabriela Fonseca Mendonça, Antonio Manzolillo Sanseverino, Marcio C. S. de Mattos* richlor isocyanuricAcidasaCohalogenatingReagent
Instituto de Química, Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, Cx. Postal 68545, 21945-970, Rio de Janeiro, Brazil Fax +55(21)25627133; E-mail: mmattos@iq.ufrj.br Received 29 May 2002; revised 11 October 2002

Abstract: The preparation of diverse b-chloroethers, b-chloroacetates, and chlorohydrins is efficiently achieved under mild conditions by reaction of alkenes with trichloroisocyanuric acid (0.34 mol equiv) in alcohols (MeOH, EtOH, i-PrOH, t-BuOH), acetic acid or aqueous acetone, respectively. Key words: alkenes, electrophilic additions, esters, ethers, halogenation

ing reagent, and we now communicate our results in this area. The results of cohalogenation of alkenes with trichloroisocyanuric acid and water to produce the chlorohydrins 2a–e are summarized in Table 1. The reactions were carried out stirring together 10 mmol of the alkene with 3.4 mmol of 1 in aqueous acetone at room temperature and after workup, the corresponding chlorohydrins were obtained in moderate to excellent yields. In general, the regioselectivity was very high and no regioisomeric products were detected by the analytical procedures employed (high-resolution GC and 1H and 13C NMR spectroscopy). Not surprisingly,16 less favourable results were obtained in terms of regioselectivity with aliphatic monosubstituted alkenes (hex-1-ene and oct-1-ene) that afforded a regioisomeric mixture of chlorohydrins in which the 1chloroalkan-2-ols predominated (ca. 3:1 by high-resolution GC). Curiously, in the reactions of styrene and a-methylstyrene a variable minor amount of halogenated alkenes was also isolated. The present method also proved suitable for the formation of b-chloroethers 2f–o and b-chloroacetates 2p–r (Table 1), as verified in the reaction of alkenes with 1 in the presence of alcohols or acetic acid, respectively. As before, the yields were moderate to good, the selectivity was very high and only in the case of oct-1-ene did the reaction give predominantly the secondary ether or acetate mixed with some of their regioisomers (ca. 3–4:1 by highresolution GC). Although we have used alcohols and acetic acid without further purification, no significant amount of chlorohydrin arising from small amounts of water in the solvent was detected by the analytical techniques employed (high-resolution CG and 1H and 13C NMR spectroscopy). In conclusion, the reaction of alkenes with trichloroisocyanuric acid is a simple method to prepare chlorohydrins, b-chloroethers, and b-chloroacetates from alkenes. The reaction conditions are mild and the method is simpler than the traditional routes employed to synthesize these compounds from alkenes. Furthermore, trichloroisocyanuric acid is a very cheap reagent that can be used in 0.34 mol equivalent; it is safer and more useful in terms of atom economy28 than traditional reagents3 used in the cohalogenation reaction.

The vicinal functionalization of alkenes is an important process in synthetic organic chemistry and several methods are described in the literature.1 Among them, the cohalogenation (halogenation of the alkene in the presence of a nucleophilic solvent) is a very useful tool to prepare vicinal difunctionalized compounds regioselectively.2 Although the reaction of chlorine with alkenes in aqueous, alcoholic or acetic media is a traditional method for the synthesis of chlorohydrins, b-chloroethers, and bchloroacetates3a respectively, the cohalogenation of alkenes with several other sources of electrophilic chlorine in an appropriate solvent can perform the same transformations.3 Trichloroisocyanuric acid (1) is a stable and inexpensive solid frequently used for swimming-pool disinfection4 and easily available in pool supply and some hardware stores. Recent examples of the utilization of trichloroisocyanuric acid in organic synthesis are N-nitrosation of N,N-dialkylamines,5 thioacetalization of carbonyl and related compounds,6 conversions of alcohols to halides and carboxylic acids to acid chlorides,7 and oxidations of alcohols to carbonyl compounds,8 aldoximes to nitrile oxides,9 thiols to disulfides,10 selenols to diselenides,11 and sulfides to sulfoxides.12 Although trichloroisocyanuric acid in now being used in various organic transformations, there are only a very few examples of its utilization for cohalogenation of carboncarbon double bonds. These include reactions with an oxazolinoazetidinone derivative,13 steroids derivatives,14 and unsaturated cyclic ethers.15 To the best of our knowledge, there is no systematic work in the literature on the utilization of trichloroisocyanuric acid as a cohalogenatSynthesis 2003, No. 1, Print: 30 12 2002. Art Id.1437-210X,E;2003,0,01,0045,0048,ftx,en;M02102SS.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0039-7881

69 (br s. in small portions.25 mm (ID). 74. 45–48 ISSN 0039-7881 © Thieme Stuttgart · New York .t. J = 11. 1 H). Trichloroisocyanuric acid (commercial grade. The organic layer was washed with H2O and then dried (Na2SO4). 3. Some selected spectral data are given below.1 (C). No. General Procedure 1 To a stirred solution of the alkene (10 mmol) in acetone–H2O (5:1. Chlorohydrins 2a–e. After the elapse of the time shown in Table 1 (the termination of the reaction was determined by the color disappearance of a wet iodine-starch test paper treated with an aliquot). OH). the product was isolated by radial chromatography on a Chromatrotron®. High-resolution GC was performed on a HP-5890-II gas chromatograph with FID using a 30 m (length). c Obtained predominantly (ca. 126. 3:1 by high-resolution GC) with its regioisomer. was added trichloroisocyanuric acid (790 mg. 7. 0. F.9 Hz. d Obtained predominantly (ca. Alcohols or Acetic Acid Product 2a 2b 2cb 2dc 2ec 2f 2g 2h 2i 2j 2k 2lb 2mb 2nb 2oc 2pb 2qd 2r a b R1 Ph Ph -(CH2)4C8H17 C6H11 Ph Ph Ph Ph Ph Ph -(CH2)4-(CH2)4-(CH2)4C6H11 -(CH2)4C6H11 Ph R2 H H R3 H Me H R4 H H H H H Me Et i-Pr t-Bu Me Et Me Et i-Pr Me Ac Ac Ac Yield (%)a 78 63 96 87 90 96 93 84 87 86 75 55 74 74 77 54 81 65 Reaction Time (min) 40 30 180 40 60 80 40 30 180 10 10 10 10 10 40 35 60 50 Reference 17 18 17 17 19 18 20 H H H H H H H H H H H H H H Me Me H H H 21 18 22 23 24 25 26 27 26 H H H H H H H Isolated yield based on alkene.88 (dd. C NMR: d = 50.2 Hz.9. respectively) spectrometer in CDCl3 solutions with TMS as internal standard. 140. 3. 1 H.4 mmol) at r. J = 11.2. After evaporation of the solvent on a rotary evaporator. and 25 mm (phase thickness) RTX-5 capillary column and H2 (flow rate 50 cm/s) as carrier gas (split: 1:10). 1. 4.72 (dd. 2a 1 H NMR: d = 2.4 Hz.4 Hz. 4.1 (CH).0 (CH).4 (CH). 4:1 by high-resolution GC) with its regioisomer. 4. trans-Product. PAPER Products 2 Obtained from the Cohalogenation of Alkenes with Trichloroisocyanuric acid (1) and Water. 129. 1 H). 1H and 13C NMR spectra were recorded on a Bruker AC-200 (200 MHz and 50 MHz. 128. CH2Cl2 (20 mL) was added and the resulting solution was treated with aq sat.5 (CH2). 3.0 (CH). NaHSO3 solution. 5 H). Mendonça et al. 1 H).35 (m. 98%) and other chemicals and solvents were used without further purification.67 (dd. 30 mL). 7.46 Table 1 G. J = 7. 13 Synthesis 2003.

1 H). Jr..0. 136. 3. A.9 (CH).72 (d. 13 2r 1 H NMR: d = 2. 1002. 1 H).4 (CH). 50. Porcheddu. 3 H). M. 3. (4) (a) Tilstam. 9. Chianelli.80 (m.15 (s. 75. 2p 1 H NMR: d = 1. 2f 1 H NMR: d = 3. 1. 70. 1 H). A. Nagata. 31. Dev.0 (CH2). Jr. 34.5 (CH).63 (m.9 (C). C NMR: d = 14. 2e 1 H NMR: d = 0. No..7. 450.. 127.2 Hz. H.. Russ. 48.. Haga. Synth. 4. 3 H). 1507. de Aguiar. 740. 140.8 (CH3). Zajac. 2. 21. 1415. M. Commun. 79.8 (C). J = 8.. 28.1. 128. using the appropriate alcohol (25 mL) instead of aq acetone.88 (m.4 Hz.00 (m. Bull. 13 Acknowledgments GFM thanks PIBIC/UFRJ and AMS thanks CNPq for fellowships.. J = 7.. J = 4.50 (dd. 3.80 (m. 1 H). J = 4. J = 6. (3) (a) Smith. 2. 13 C NMR: d = 25. R. R. 1 H. 3. (11) Zhong. 126.0 (C=O).38 (dq. 77. P.4 (CH2). 1 H). Heterocycles 1981. P.. W. 50. A.8 Hz. Laroche. 2. 1 H).8 (CH). Synth. (6) Firouzabadi. 171. C. K. 128. X.0 Hz. J = 4. J. 2001. 41. 1 H). Chem.. 2. 5 th ed. Chim.39–7. Bruce Kover for helpful discussions. 53.8 (CH3).7 (CH2). 1 H). 1584. 22. 3 H). J. Synthesis 2003..5 (CH2). 25. 1177. C NMR: d = 15. (9) Rodrigues. 141. (14) (a) Mukawa. Chem. 2 H).3 (C). J = 11. 1641. 1 H). G. 1999. 127. P. March’s Advanced Organic Chemistry.. 54. Woods. 78. Org.8 (CH2).30–2. H. 1. 46. J = 4. M. M. Chem. Synth.3 (CH). 5209... Commun.. 3.80 (m.. Synlett 2002. Lett. A.. Spangler. Ducan. Quim. S.60 (br s.0 Hz.5 (CH2). 1 H).4 (C).23 (d.8 (CH). 3 H).4 Hz. 7. 13 2d 1 H NMR: d = 0.2 (CH2). Synthesis 1998. 2 H). Commun..0. 1964. Guo.65 (dd. M. E. 3. 1 C NMR: d = 20. and Structure. J = 11. Nova 2001. 128.3 Hz. 31. 1 H). Synlett 2001.00 (dd. 1 H). 2002.5. 920.60 (d.5 (CH). 13 b-Chloroethers 2f–o. (12) Xiong. References (1) Iranpoor. Z. J = 4.55 (dd. 33.30 (s. R. Synthesis 1993. F. S. T. W. (20) Uemura.55 (d. 3 H). 3.2 (CH3). 56. Abstr. B. 6. Synth. P.. 15. T. Hazarkhani. Org. 1 H).1 (CH). 31. de Mattos. 2001.40 (br s. A Guide to Functional Group Preparations. Bull. 1991. 3.7 (C). OH).3 (CH). M.35 (m. 1 H).39 (s. G. J = 11.6 (CH)..4 (CH3). A. J. (b) Sanseverino. J = 10. 12.. 47. Tetrahedron 1998. J = 5.2 (CH). OH)..2 (CH2). 384.0 (CH2).9 (CH2). 8. 3.6 (CH2). 129. 1 H). Org. Commun. D. 8 H).10–1. 3836. U. 24. Huang. Shekarriz. 1 H).84 (m. 25. 2001. 126. W. 5 H).38 (s. 3. 1043–1044. (b) Mukawa. General Procedure 2 The reaction was carried out in an analogous manner as described for General Procedure 1.7 (CH2). C NMR: d = 14. J = 11. M. 3. 3. 5 H). Tetrahedron 1988.7 (CH3). J. 83.0 (CH2). 31. F. 22.0 (CH3). OH). D. 128. 53. 21.60 (dd.90 (dd. 170. 2001. 2. J = 11. C. 5 H). 6 H).90 (m. N. 29282. Yoshioka. 3. (c) Walters.57 (dd. 13 C NMR: d = 20.. J. 1825.5 (CH). March. 3041. 127. (b) Sanseverino. 129. (15) Juenge. 325–329. 78. 4. 7.20 (br d. J = 11.2 Hz. Ramirez. Testaferri. Weinmann.. 9.19 (dq. 3 H). 2001. (10) Zhong. 1 H).6 (CH2). J = 6.40 (br s.5 (CH).4 (CH2). Some selected spectral data are given below. W. 1992. 5.7 Hz. 138. 142. M.35 (dd. (5) Zolfigol. J = 8.61 (s. Guo.7 (CH). Mechanism. M. We thank Joel Jones Jr. 5 H). M.0. OH).3 Hz. 33.7 (CH).0 (CH3).70 (br s. 7. 1974.19 (t. N. Wiley-VCH: New York. Nippon Kagaku Zasshi 1957. 73. 409. 3 H).46 (dd.0 Hz.30 (s. 35. Kamata. 127.4 (CH). 5. M.. L. 29. G. 2709. Jpn. L.7 (CH). A. M. P. 1240. 1 13 C NMR: d = 21.. 52. 45–48 ISSN 0039-7881 © Thieme Stuttgart · New York . P.PAPER Trichloroisocyanuric Acid as a Cohalogenating Reagent 47 2b 1 H NMR: d = 1. Barr. Soc. 3 H). 2h H NMR: d = 1.1 (CH2). 127. J..3 (CH). 1966. A. 5 H).51 (m. 25. Ohshima. 3. Abstr..32 (m.0 Hz. Commun. 3.1 (CH2). T. 1. 10 H). General Procedure 3 The reaction was carried out in an analogous manner as described for General Procedure 1. (b) Larock. S.. J = 8.9 (CH). S. 7.6 (C). Zushi. Toshimitsu.7. 3075. 5 H).-P.3 (CH2).. M. 53. Fujiwara. 3. J.5.. 1972. 128. 137. 3 H). Choghamarani. 1 H). Okano. da Silva. 1959. Giacomelli.0 (CH3). L. (18) Tiecco. 1 H).. 2001. Shimanouchi. 1. C NMR: d = 24. 3. 1589. Chem.2 Hz. (2) (a) Rodriguez.78 (d.6 (CH2). (8) De Luca. Chem.8 (CH). 6 H). N. 55.0 (CH2). (b) Hiegel. 637.9 (CH). 245. 53319.5 Hz. 2261. 71. 4. Bull. 56..4 Hz. Jpn. 13 C NMR: d = 48.3 (C). 1 H). 29. 71. 31.6 (CH2). J = 4. 7. B. 23.7 (CH).2 Hz. 13 2k 1 H NMR: d = 1. 3. Bartoli. C NMR: d = 21. (19) Blouri. de Mattos. 124. 22. 3 H).1 (CH3). 3 H).0 Hz. 1.05–2. 27. 2001. 13 b-Chloroacetates 2p–r. Konoike.52–1. 128. 57.00 (s. R. T. Jones. H.8 (C). 126. and W. N..0 Hz. 3.72–3.70 (m. Hazarkhani. (17) Kotsuki. Fr. 44. 2c 1 H NMR: d = 1.. 12. Nalbandy..7 (CH2). 1 H). 3. J = 11. 1 H). 3..4 (CH).9.0 (CH). G.1 (C=O).. P. Commun. 316. J.2 Hz. Comprehensive Organic Transformations. Synth.2 (CH3)..6 (CH2).8 Hz. Process Res. 3.4 (CH3).7 (CH). Rev. M.0 Hz. Org. 1 H). P.5 Hz.4 Hz.4 Hz.2.15 (s.2 Hz.72 (s. M. Tetrahedron 2000. P. 67.2 (CH2). S. Tabata.77 (d. 3.9. H. 26.40–7.6 (CH2).0 (CH). J = 11. J = 7. A. WileyInterscience: New York. Synth. using HOAc (25 mL) instead of aq acetone. F.0 (CH). 31. R. 2j H NMR: d = 1. 1 H. (7) Hiegel. 1960. 1 H)... (13) Aoki. A.14 (d. 58. C.62 (dd. 34.9 (CH). Iranpoor. J = 5. 50. D. Tingoli.8 (CH3). C. J = 10. 22. M. 1 H.8.71 (d. 1 H. 3 H). Chem. 126. 7.68 (s. H. 7. Soc. (16) (a) Boguslavskaya.7 (C). Soc. K. 2.. Dulcere. Some selected spectral data are given below. 4. Reactions. S. 1989. M.25 (br d. A. 3. L. 144. 7. 7.. 78.25 (m. Chem.98 (dd. 75.. 3.81 (d. Rumpf.

Chem.. M..48 G. F.. (27) Backvall.. Commun. Pritzkow. (26) Quian.. Martin.. (23) Dinulescu. C. Synth. Quim. 39. C. 317. M. Synthesis 2003. Tetrahedron Lett. E. Farcasiu. J. J. A.. J. PAPER (25) Duschek. 132. Chem. C. 3523. Oakes. 840. Chem. Nenitzescu. Robinson. Org. B. Gipe. K. Sharpless. C. 102. F. Ullmann. 2000.. Org. 1962. J.. Hampel. 23. G. (22) Heasley. Science 1991.. T. 394. Jijovici. M. B.. M. Prakt. T. B. 48. 24. Shellhamer. M.. 1. C. 1977. Zhu. W. R. A. Nova 2000. J. 2203. 1980. 1974. Young. H. R. 254. Jacobi. W. 335. (24) Walling. 1994. Chem.. M. Chem... 1975. V. Chem. (28) (a) Trost. Storch. E. Mendonça et al... G. D. C. K. R. (b) Sanseverino. M. No. H.. L. L.. Heasley. (London) 1964. L. D. 3195. 1471. L. Wiese. (21) Beger. Ind. 236563. I. Abstr. D. J. 45–48 ISSN 0039-7881 © Thieme Stuttgart · New York .. Clark. M. J. 1983. Prakt. 322. Avram.