[4 + 2]-Cycloaddition Reactions Involving α-oxo Thioketone Intermediates

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1 [4 + 2]-Cycloaddition Reactions Involving α-oxo Thioketone Intermediates Mohamed I. Hegab, Abd El-Galil A. Amr, and Farouk M. E. Abdel-Megeid National Research Centre, Dokki, Cairo, Egypt Reprint requests to F. M. E. Abdel-Megeid. faroukezat@yahoo.com Z. Naturforsch. 57 b, 922Ð927 (2002); received December 10, 2001 Oxo Thioketone Intermediates, 1,3,4-Oxadithiins, 3 -Thiopyran Derivatives α-chloro β-oxo sulfenyl chlorides 2 were reduced by iodide ions to the corresponding α-oxo thioketones 3 which dimerized in situ in a hetero-[4 + 2] cycloaddition to give the 1,3,4- oxadithiin derivatives 4. Theα-oxo thioketones 3, in situ, cyclized also with 2,3-dimethyl-1,3- butadiene to give the corresponding adducts 5 and only in case of the oxo thioketone intermediate 3d two products 4d and 5d were obtained. Also, The α-oxo thioketones 3a,c, underwent in situ, cycloaddition with furan to give the corresponding adducts 6a,c together with the corresponding thioketone dimers 4a,c. When this reaction was carried out in the presence of diethyl acetylenedicarboxylate or chalcone derivative 8, only the oxo thioketone dimers 4aÐd were obtained. α-oxo thioketones have been generated from thiirane S-oxides by simultaneous generation of the oxo and the thioxo group [1]. Upon photolysis 1,2- dibenzoyl-1,2-diphenylthiirane S-oxide is cleaved to form a mixture of benzil and monothiobenzil (Scheme 1, eq. (1)). Jacobsen et al. [2a] have reported the generation of α-oxo thioketones from α-thiocyanato ketones (eq. (2)). Also, α-oxo thioketones can be prepared from the reaction of 1,2- dicarbonyl or α-hydrazono carbonyl compounds with dichlorodisulfane [2a]. Monothioacenaphthenequinone can be prepared from acenaphthenequinone and Lawesson s reagent (LR) [2b] (eq. (3)). Recently, α-oxo thioketones in the dimeric form were prepared from the reaction of α-chloro-α-chlorothio carbonyl compounds with tertiary phosphines or potassium iodide [3, 4] (eq. (4)). α-oxo thioketone compounds are stable in many cases and can be isolated in pure state in the monomeric form [6Ð12]. In previous papers, we [3] and others [4,5] have reported the isolation of the α-oxo thioketones in the dimeric state. Therefore, we are interested to investigate such reactions in the presence of an external diene or dipolarophile. Results and Discussion Starting from 4-oxochromane derivatives 1aÐd, the α-chlorosulfenyl chlorides 2aÐd were prepared by a known procedure [14] (Scheme 2). Compound 2d was not described in the literature before, however we report here its preparation and identification by elemental analysis and spectral data (IR, 1 H NMR and MS). Upon treatment of compound 2d with potassium iodide under stirring for 1 h at 20 C, it gave the corresponding 1,3,4-oxadithiin 4d through the intermediacy of the α-oxo thioketone 3d. The structure of 4d follows from assignments for compounds 4aÐc [3Ð5]. The 13 C NMR spectrum of 1,3,4-oxadithiin 4d showed signals for twelve CH 2 carbon atoms, for the three spiro carbons (δ = 83.67, 87.93, 92.52), for the two sp 2 -carbons in the oxadithiin ring (C-4a and C-10b, respectively) (δ = , ), and for the carbonyl carbon (C-4 ). These data exclude the formation of the possible [10, 12, 13a,b] 1,3-dithietanes resulting from dimerization across the C=S bond of thioketones 3. When compounds 2aÐd were treated with potassium iodide in the presence of 2,3-dimethyl-1,3- butadiene, α-oxo thioketones 3 reacted with the diene to give 3 -thiapyran derivatives 5aÐd. In case of 2d the cycloadduct 5d was obtained together with the oxadithiin 4d (Scheme 2). The structures of 5aÐd were established by elemental analyses and spectral data. The 1 H NMR spectra of 5aÐd showed two doublets at δ = 2.66Ð 2.57 and at δ = 2.84Ð2.79 ppm (J = 13.5Ð17.5 Hz) corresponding to the 2-CH a H b protons and a multiplet at δ = 2.01Ð2.49 ppm corresponding to 5-CH 2 protons. Actually, product 5b is expected to 0932Ð0776/2002/0800Ð0922 $ Verlag der Zeitschrift für Naturforschung, Tübingen D

2 M. I. Hegab et al. Cycloaddition Reactions Involving α-oxo Thioketone Intermediates 923 be formed as diastereomers. However, the 1 H Scheme 1. NMR (cf. Experimental part) exhibited clearly the signals of only one diastereomer. If the minor diastereomer was present, its concentration was too small to be detected. 13 C NMR of 5a shows signals at δ = 19.16, 19.88, 20.96, (4 CH 3 ), 28.68, (5-CH 2 and 2-CH 2 ), 56.50, (C-3 and C-2 ), , for the two sp 2 carbons of thiapyrane ring (C-4 and C-3), , , , , , (ArÐC) and for the carbonyl carbon (C-4 ). The mass spectra of 5aÐd showed the molecular ion peaks as parent peaks. IR spectra of 5aÐd showed ν C=O = 1683Ð 1681 cm Ð1. The reactions of thiooxo compounds with furan, to our knowledge, have not been reported. Treatment of 2a,c with potassium iodide in the presence of furan gave the [4 + 2] cycloaddition products 6a,c, together with the α-oxo thioketone dimers 4a,c, respectively, (Scheme 1). The structures of 6a,c were verified by elemental analyses and spectral data. For example, the 1 H NMR spectrum of compound 6a showed signals at δ = 6.29 (d, J =

3 924 M. I. Hegab et al. Cycloaddition Reactions Involving α-oxo Thioketone Intermediates Scheme Hz, 4-H) and 6.67 (d, J = 3.3 Hz, 1-H). The 13 C NMR spectrum of 6a showed signals at δ = 22.99, (2 CH 3 ), 66.83, (C-3 and C-2 ), (C-4), (C-1), , for the two sp 2 carbons of the oxathiabicycloheptene ring (C-5 and C-6), , , , , , (ArÐC) and (C-4 ). The mass spectra of 6a,c showed M + ÐH as the parent peak. To our knowledge, the oxathiabicyclo[2.2.1]heptene ring system of products 6a,c has not been described in the literature before. The reaction of 2aÐd with potassium iodide in the presence of diethyl acetylenedicarboxylate or chalcone derivative 8 did not lead to the expected corresponding [1,4]oxathiino[3,2-c]benzopyrane derivatives 7 and 9, but rather to the corresponding oxo thioketone dimers 4aÐd. Experimental Section The melting points are uncorrected. Microanalyses were perfomed by the central services laboratory, National Research Centre, Cairo. IR spectra were obtained with a PU 9712 infrared spectrophotometer for neat samples (for liquids) or KBr wafers (for solids). 1 H NMR and 13 C NMR spectra were taken in CDCl 3 as solvent with a JEOL EX

4 M. I. Hegab et al. Cycloaddition Reactions Involving α-oxo Thioketone Intermediates MHz spectrometer (National Research Centre) and with a Varian Mercury 300 MHz spectrometer (Cairo University, Faculty of Science). EI (70 ev) mass spectra were recorded on a G. C. MSQP 1000 Ex Shimadzu spectrometer in National Research Centre, Dokki, Cairo. Compounds 1a,b [5] 1c [15] 1d [16] 2aÐc [14] 4aÐc [3Ð5] were prepared according to the literature. Yields of the products were reported after purification either by recrystallization or column chromatography separation. 3-Chloro-3-chlorosulfenylspiro[chroman-2,1 cycloheptane]-4-one (2d) Spiro[chroman-2,1 -cycloheptane]-4-one (1d) (13.8 g, 60 mmol) was dissolved in thionyl chloride (30 ml) and stirred for 15 h. Removal of the excess thionyl chloride afforded a dark brown viscous oil which crystallized in needles upon standing. Recrystallization from diethyl ether Ð n-hexane (1:5) afforded 14 g (70%) of 2d. Ð M.p. 89Ð 91 C. Ð IR (film): ν = 1700 cm Ð1 (C=O). Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.23Ð2.22 (m, 12 H, cycloheptane ring), 6.90 (d, J = 8.1 Hz, 1 H, ArÐ H), 7.05 (t, 1H, ArÐH), 7.52 (t, 1H, ArÐH), 7.88 (d, J = 8.1 Hz, 1 H, ArÐH). Ð MS (EI, 70 ev): m/ z (%) = 334 (8) [M +, 2 Cl 37 ], 332 (40) [M +, Cl 35 Cl 37 ], 330 (58) [M +,2Cl 35 ], 297 (35) [MÐCl 37 ], 295 (100) [MÐCl 35 ], 277 (97), 259 (31), 215 (38), 211 (15), 175 (17), 166 (27), 139 (27), 121 (80). Ð C 15 H 16 Cl 2 O 2 S (331.25): calcd. C 54.38, H 4.87, S 9.68; found C 54.59, H 5.07, S Trispiro[cycloheptane-1,5 Ð2H-chromeno[3,4-e]- [1,3,4]oxadithiin-2,3 -chroman-2,1 -cycloheptane]-4 -one (4d) A solution of KI (0.5 g, 3 mmol) in CH 3 CN (30 ml) was added to a solution 2d (0.9 g, 3 mmol) in CHCl 3 (10 ml) under stirring. After another 1 h of stirring the reaction mixture was treated with aqueous Na 2 S 2 O 3, the organic phase was separated and dried over Na 2 SO 4. After evaporation of the solvent in vacuo the solid residue was triturated with diethyl etherðn-hexane (1:10) to give 4d which was further recrystallized from n-hexane to afford 0.6 g (40%). Ð M.p. 146Ð149 C. Ð IR: ν = 1704 cm Ð1 (C=O). Ð 1 H NMR (300 MHz, CDCl 3 ): δ = 1.36Ð1.95 (m, 16 H, 8 CH 2 ), 2.04Ð 2.34 (m, 8 H, 4 CH 2 ), 6.76Ð7.02 (m, 4 H, ArÐH), 7.09Ð7.29 (m, 2 H, ArÐH), 7.45 (t, 1H, ArÐH), 7.85 (d, J =8.0Hz,1H,ArÐH). Ð 13 C NMR (75 MHz, CDCl 3 ): δ = 22.27, 22.33, 22.59, 23.07, 28.80, 29.23, 29.26, 29.40, 32.13, 35.29, 37.90, 38.10, 83.67, 87.93, 92.52, , , , 11.41, , , , , , , , , , , Ð MS (EI, 70 ev): m/z (%) = 520 (26) [M + ], 260 (10) [C 15 H 16 O 2 S], 203 (16), 120 (59), 92 (100). Ð C 30 H 32 O 4 S 2 (520.68): calcd. C 69.19, H 6.19, S 12.31; found: C 69.23, H 6.49, S Reaction of 2 with potassium iodide in the presence of 2,3-dimethyl-1,3-butadiene General procedure A solution of KI (10 mmol) in CH 3 CN (100 ml) was added to a solution of compounds 2aÐd (10 mmol) in CHCl 3 (20 ml) containing an excess of 2,3-dimethyl-1,3-butadiene (30 mmol) under stirring. After another 1 h of stirring the reaction mixture was treated with aqueous Na 2 S 2 O 3, the organic layer was separated and dried over Na 2 SO 4. After evaporation of the solvent in vacuo the residue was purified by column chromatography (Silica gel Merck 60, particle size 0.06Ð 0.2 mm, as the stationary phase and diethyl etherð n-hexane (1:10) as the eluent) to give the cycloadducts 5aÐd, respectively. 2,2,3,4-Tetramethyl spiro[chroman-3,6-3 thiopyrane]-4 -one (5a) From 2a, yield 1.8 g (64%). Ð M.p. 99Ð101 C. Ð IR: ν = 1681 cm Ð1 (C=O). Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.27 (s, 3 H, CH 3 ), 1.57 (s, 3 H, CH 3 ), 1.62 (s, 3 H, CH 3 ), 1.68 (s, 3 H, CH 3 ), 2.01Ð2.26 (m, 2 H, 5-CH 2 ), 2.57 (d, J = 15 Hz, 1 H, 2-CH a H b ), 2.79 (d, J = 15 Hz, 1 H, 2-CH a H b ), 6.75 (d, J =8.1Hz,1H,ArÐH), 6.90 (t, 1 H, ArÐH), 7.32 (t, 1 H, ArÐH), 7.78 (d, J = 8.1 Hz, 1 H, ArÐH) C NMR (68 MHz, CDCl 3 ): δ 19.16, 19.88, 20.96, 23.18, 28.68, 32.40, 56.50, 83.58, , , , , , , , , Ð MS (EI, 70 ev): m/z (%) = 288 (100) [M + ], 273 (84), 241 (26), 173 (17), 168 (23), 161 (24), 153 (26), 135 (62), 125 (16), 121 (51). Ð C 17 H 20 O 2 S (288.39): calcd. C 70.79, H 6.99, S 11.11; found: C 70.39, H 6.74, S Ethyl-2,3,4-trimethyl spiro[chroman-3,6-3 thiopyrane]-4 -one (5b) From 2b, yield 2.0 g (66%). Ð Oil. Ð IR: ν = 1681 cm Ð1 (C=O). Product 5b is expected to be formed as diastereomers. However, the 1 H NMR spectrum of the product exhibited clearly the signals of only one diastereomer. Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.10 (t, 3 H, 2-CH 2 CH 3 ), 1.26 (s, 3 H, CH 3 ), 1.49Ð1.70 (m, 2 H, 2- CH 2 CH 3 ), 1.73 (s, 6 H, 2 CH 3 ), 2.22Ð2.45 (m, 2 H, 5-CH 2 ),

5 926 M. I. Hegab et al. Cycloaddition Reactions Involving α-oxo Thioketone Intermediates 2.64 (d, J = 17.5 Hz, 1 H, 2-CH a H b ), 2.84 (d, J = 17.5 Hz, 1 H, 2-CH a H b ), 6.86 (d, J = 8.1 Hz, 1 H, ArÐH), 6.96 (t, 1 H, ArÐH), 7.42 (t, 1 H, ArÐH), 7.86 (d, J = 8.1 Hz, 1 H, ArÐH). Ð MS (EI, 70 ev): m/z (%) = 302 (50) [M + ], 273 (100), 241 (26), 173 (12), 168 (23), 153 (26), 135 (62), 121 (30). Ð C 18 H 22 O 2 S (302.42): calcd. C 71.48, H 7.33, S 10.60; found: C 71.23, H 6.93, S ,4-Dimethyl dispiro[cyclohexane-1,2 -chroman- 3,6-3 thiopyrane]-4 -one (5c) From 2c, yield 2.8 g (85%). Ð M.p. 110Ð 113 C. Ð IR: ν = 1683 cm Ð1 (C=O). Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.37Ð2.00 (m, 16 H, 10 HÐcyclohexane + 2 CH 3 ), 2.19Ð2.41 (m, 2 H, 5-CH 2 ), 2.66 (d, J = 13.5 Hz, 1 H, 2-CH a H b ), 2.81 (d, J = 13.5 Hz, 1 H, 2-CH a H b ), 6.90Ð7.05 (m, 2 H, ArÐH), 7.44 (t, 1 H, ArÐH), 7.87 (d, J = 8.1 Hz, 1H,ArÐH). Ð MS (EI, 70 ev): m/z (%) = 328 (100) [M + ], 313 (12), 295 (22), 285 (16), 208 (13), 174 (21), 121 (27). Ð C 20 H 24 O 2 S (328.45): calcd. C 73.13, H 7.36, S 9.76; found: C 73.18, H 7.64, S ,4-Dimethyl dispiro[cycloheptane-1,2 -chroman- 3,6-3 thiopyrane]-4 -one (5d) The reaction of 2d with KI in the presence of 2,3-dimethylbutadiene gave a mixture of 4d and 5d which were separated by column chromatography (silica gel Merck 60, particle size 0.06Ð0.2 mm, and diethyl etherðn-hexane (1:10) as the eluent). 4d: 0.3 g (20%). Ð M.p. 146Ð149 C. 5d: Yield 1.36 g (40%). Ð M.p. 84Ð87 C. Ð IR: ν = 1681 cm Ð1 (C=O). Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.37Ð2.04 (m, 18 H, 12 HÐcycloheptane + 2 CH 3 ), 2.19Ð2.48 (m, 2 H, 5-CH 2 ), 2.64 (d, J = 13.5 Hz, 1 H, 2-CH a H b ), 2.84 (d, J = 13.5 Hz, 1 H, 2-CH a H b ), 6.89Ð7.01 (m, 2 H, ArÐH), 7.42 (t,1h,arðh), 7.87 (d, J = 8.0 Hz, 1 H, ArÐH). Ð MS (EI, 70 ev): m/z (%) = 342 (100) [M + ], 309 (42), 295 (17), 285 (18), 221 (14), 173 (20), 120 (53). Ð C 21 H 26 O 2 S (342.48): calcd. C 73.64, H 7.65, S 9.36; found: C 73.44, H 7.53, S Reaction of 2a,c with potassium iodide in the presence of furan General procedure A solution of KI (5 mmol) in CH 3 CN (50 ml) was added to a solution of compound 2a or 2c (5 mmol) in CHCl 3 (10 ml) containing an excess of furan (25 mmol) under stirring. After another 1 h of stirring, TLC indicated that two products were formed. The reaction mixture was treated with aqueous Na 2 S 2 O 3, the organic layer was separated and dried over Na 2 SO 4. After evaporation of the solvent in vacuo the two products were separated by column chromatography (silica gel Merck 60, particle size 0.06Ð0.2 mm, diethyl etherðn-hexane (1:20) as the eluent). 2,2 -Dimethyl spiro{chroman-3,3-(7-oxa-2-thiabicyclo[2.2.1]hept-5-ene)}-4 -one (6a) The reaction of 2a with KI in the presence of furan gave a mixture of 4a and 6a which were separated by using column chromatography (silica gel Merck 60, particle size 0.06Ð0.2 mm, and diethyl etherðn-hexane (1:20) as the eluent). 4a: 0.51 g (50%). M.p. 145Ð147 C (lit. [4]: 145Ð147 C). 6a: yield 0.32 g (24%). Ð M.p. 155Ð157 C. Ð IR: ν = 1687 cm Ð1 (C=O). Ð 1 H NMR (300 MHz, CDCl 3 ): δ = 1.27 (s, 3 H, CH 3 ), 1.51 (s, 3 H, CH 3 ), 6.29 (d, J = 3.3 Hz, 4-H), 6.67 (d, J = 3.3 Hz, 1-H), 6.89 (d, 1H, J = 8.1 Hz), 7.02Ð7.14 (m, 3 H), 7.46Ð 7.51 (m, 1 H), 7.99 (d, J = 7.8 Hz, 1 H). Ð 13 C NMR (CDCl 3, 75 MHz): δ 22.99, 25.26, 66.83, 83.89, , , , , , , , , , , Ð MS (EI, 70 ev): m/z (%) = 273 (100) [M + Ð H], 258 (18), 255 (12), 241 (30), 207 (68), 184 (11), 176 (22), 161 (33), 153 (94), 121 (92). Ð C 15 H 14 O 3 S (274.32): calcd. C 65.67, H 5.14, S 11.68; found: C 65.34, H 4.86, S Dispiro{cyclohexane-1,2 -chroman-3,3-(7-oxa-2- thiabicyclo[2.2.1]-hept-5-ene)}-4 -one (6c) The reaction of 2c with KI in the presence of furan gave a mixture of 4c and 6c which were separated by using column chromatography (silica gel Merck 60, particle size 0.06Ð0.2 mm, and diethyl etherðn-hexane (1:20) as the eluent). 4c: 0.40 g (33%). Ð M.p. 125Ð127 C (lit.[3] 125Ð127 C). 6c: yield 0.21 g (18%). Ð Oil. Ð IR: ν = 1987 cm Ð1 (C=O). Ð 1 H NMR (270 MHz, CDCl 3 ): δ = 1.19Ð2.19 (m, 10 H, cyclohexaneðh), 6.38 (d, J = 3.3 Hz, 4-H), 6.69 (d, J = 3.3 Hz, 1-H), 6.85 (d, 1H, J = 8.1 Hz), 6.98Ð7.15 (m, 3 H), 7.42Ð7.59 (m, 1 H), 7.92 (d, 1 H, J = 7.8 Hz). Ð MS (EI, 70 ev): m/z (%) = 313 (46) [M + ÐH], 295 (4), 247 (20), 213 (21), 193 (40), 185 (16), 173 (14), 121 (100). Ð C 18 H 18 O 3 S (314.38): calcd. C 68.76, H 5.77, S 10.19; found: C 68.59, H 5.49, S 9.76.

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