Pinacol coupling of aromatic aldehydes and ketones mediated by TiCl 4 -Zn in ethyl acetate under ultrasound

Transcription

1 Indian Journal of hemistry Vol 46B, August 2007, pp Papers Pinacol coupling of aromatic aldehydes and ketones mediated by l 4 -Zn in ethyl acetate under ultrasound Ji-Tai Li *, Xue-Li Sun, Zhi-Ping Lin, Yan-Xue hen & Tong-Shuang Li Department of hemistry, ollege of hemistry and Environmental Science, ebei University, Baoding , P R hina lijitai@mailhbueducn Received 13 January 2006; accepted (revised) 16 May 2007 Zinc powder can reduce titanium tetrachloride to the corresponding low valent titanium complexes, which can promote coupling of some aromatic aldehydes and ketones to the corresponding pinacols in 35-99% yield in ethyl acetate at o within min under ultrasound irradiation Keywords: Pinacol coupling, aromatic aldehydes, ketones, ultrasound irradiation The reductive coupling of aldehydes and ketones to give diols is a powerful method for constructing vicinal functional carbon-carbon bonds 1, which has been employed successfully in synthesis of many natural products and asymmetric ligands 2 In the past years, various metal reagents and their complexes have been tried for mediating pinacol coupling reactions, such as Mg 3, Mn 4, Al 5, In 6, SmI 7 2, Zn 8, 9 pv() 4, 10 and rare earth metal Recent efforts have focused on the development of new reagents and reaction systems to improve the reactivity of the reagents and diastereoselectivity of the products Low valent titanium complexes are highly reactive reagents and have attracted interest in carbonylcoupling reactions 14 Pioneering work by Mukaiyama 15 in 1973, reported that l 4 -Zn reduced aromatic aldehydes and ketones to gain the corresponding 1,2-diols in high yields Following Mukaiyama, reports about low valent titanium catalyzed pinacolization appeared increasingly lerici et al reported pinacol coupling of aromatic aldehydes and ketones promoted by titanium trichloride in 1982 (ref 16) and 1996 (ref 17) respectively Though the reaction was completed with high dl-stereoselectivity, aromatic aldehydes bearing an electron-donating group showed lower reactivity In 2000, Li et al 18 reported that 1,2-diols were obtained in pinacol coupling mediated by l 4 -Mg with a high stereoselectivity In 2001, Yamamoto et al 19 reported diastereoselective pinacol coupling of aldehydes promoted by the monomeric titanocene(iii) complex p 2 Ph In 2004, Li et al 20 reported the pinacolization of aldehydes by l 4 (TF) 2 with a titanium-schiff base complex, which afforded pinacols in 82-95% yield In spite of their potential utility, some of the methods reported suffer from drawbacks such as longer reaction time, more expensive reagents, and lower yields Ultrasound has increasingly been used in organic synthesis in the last three decades omparing with traditional methods, this technique is more convenient and easily controlled A large number of organic reactions, especially many metal-involved reactions, can be carried out with higher yields, shorter reaction time and milder conditions under ultrasound irradiation The pinacolization of some aromatic aldehydes and ketones by low valent titanium under ultrasound irradiation 21,22 has also been reported, but the solvent used was 2 l 2 which is toxic and harmful to the environment Ethyl acetate is a safe, available and environmentally benign solvent erein, the pinacol coupling reaction mediated by l 4 -Zn in ethyl acetate under ultrasound irradiation (Scheme I) is also reported Results and Discussion As shown in Table I and Scheme I, pinacol coupling of some aromatic aldehydes and ketones was carried out in good yield using l 4 -Zn in ethyl acetate under ultrasound irradiation A number of variables such as molar ratio of l 4 /Zn/substrate, irradiation frequency, the p value of medium, and

2 1304 INDIAN J EM, SE B, AUGUST 2007 R 1 l 4 -Zn 3 Et, us R 1 R 1 + R 1 Scheme I Table I The effect of the reaction conditions on pinacol coupling of benzaldehyde under ultrasound irradiation a Entry Molar ratio of l 4 /Zn/Ph Irradiation frequency (Kz) me (min) Isolated yield (%) a 3:4:1 stir b 3:4: c 2:4:1 stir d 2:4: e 1:4:1 stir f 1:4: g 2:3:1 stir h 2:3: i 2:5:1 stir j 2:5: k 2:4: l 2:4: m 2:4: n 2:4: o 0:4: b p 2:4: c a Reaction temp o ; p of medium: 2-3 b Without l 4, Zn/Ph=4:1 c The substrate is p-l 6 4 use of mechanical stirring or ultrasound may all have an influence on the reaction The influence of the reaction conditions on pinacol coupling of benzaldehyde under ultrasound irradiation is shown in Table I ompared with the stirring method, the coupling reaction can be accelerated under ultrasound irradiation For example, the yield of 1,2-diphenyl-1,2-ethanediol was 75% (Entry d) under ultrasound irradiation, while it was only 60% (Entry c) by using stirring The reason may be that ultrasonic irradiation can cause Zn particle rupture, and the decrease in particle size thus increases the surface area available for reaction 23,24, which can reduce 4+ to low valent titanium complexes rapidly It is not clear why prolonging the reaction time from 40 to 80 min gave a lower yield of 1,2-diphenyl-1,2- ethanediol (Entry d, l) When the molar ratio of l 4 /Zn/Ph was 2:4:1, 1,2-diphenyl-1,2-ethanediol was obtained in 75% yield (Entry d) It was found that changing the molar ratio of l 4 in l 4 /Zn/Ph from 2:4:1 to 3:4:1 and 1:4:1, the yield of pinacol decreased from 75% (Entry d) to 71% (Entry b) and 66% (Entry f) respectively With increase of Zn in the l 4 /Zn/Ph molar ratio to 2:5:1 or decrease to 2:3:1, the yields of 1,2-diphenyl-1,2-ethanediol were both 67% (Entry h, j) In the absence of l 4, 1,2- diphenyl-1,2-ethanediol was only obtained in 7% yield (Entry o) It is clear that the ratios of l 4 and Zn both have a significant influence on the yield of pinacol coupling We also observed the effect of different frequency of ultrasound irradiation on the coupling reaction When the pinacol coupling reaction was carried out under 25 Kz, the desired product was obtained in 75% yield within 40 min (Entry d) Increasing the frequency of ultrasound irradiation from 25 Kz to 40 Kz and 59 Kz could not accelerate the pinacolization, but decreased the yield of pinacol from 75% (Entry d) to 69 and 68% (Entry m, n) The reason may be that higher frequencies of ultrasound irradiation produce worse cavitations 25 Therefore all other couplings were carried out under 25 Kz ultrasound irradiation From the above results, the reaction conditions were chosen as: l 4 (2 mmoles), Zn (4 mmoles), aldehyde or ketone (1 mmole), 3 Et (5 ml), p=8-9, and frequency of ultrasound irradiation 25 Kz We did a series of experiments for pinacol coupling of various aromatic aldehydes and ketones The results are summarized in Table II It is known that pinacol coupling reaction of the aromatic aldehyde and ketone 1 mediated by low valent titanium can form pinacol 2 and alcohol 3 From the data given in the Table II, the l 4 -Zn- 3 Et system has high chemoselectivity for various aromatic aldehydes and ketones, especially for 3,4-( 2 ) 6 3 (1g), (1f), and 3-l 6 4 (1b), given the desired 1,2- diols with 99% (2g), 86% (2f), and 86% (2b) yields respectively within min Moreover, the electronic effect of substituents in the aromatic ring seems to have no effect on the yield of pinacol

3 Li et al: PINAL UPLING F ARMATI ALDEYDES AND KETNES 1305 owever, under acidic conditions reported 26,27, the aldehydes bearing electron-donating groups have shown lower reactivity in pinacolizations In addition, the aldehydes and ketones with p-alkoxyl groups have higher diastereoselectivity, for instance, the ratios of dl/meso of 1f, 1g and 1j are 84:16, 29:71 and 32:68 respectively In the present procedure, pinacol coupling of some aromatic ketones (1h, 1g) was obtained in good yields Improved yield of pinacol has been observed in basic medium When the p value was changed from 2-3 to 8-9, the yield of 1,2-di(p-chlorophenyl)-1,2- diol was increased from 56 to 80% (Table I, Entry p) (Table II, 2c) When the p value reached 12-13, the yield of 1,2-di(p-chlorophenyl)-1,2-diol was only 73% (Table II, 2c,d) It is apparent that the yield of pinacol strongly depends on p of the medium It is worthy to note that the order of adding Na aqueous solution to the reaction system is crucial The Na aqueous solution must be added to the flask prior to the substrate; otherwise, no product is obtained Table II Pinacol coupling reaction mediated by l 4 -Zn- 3 Et under ultrasound irradiation in basic media a Entry Substrate 1 me (min) Isolated yield (%) dl/meso b 2 3 a Ph :43 b 3-l :47 c 4-l : c d 1 d :57 e :43 f :16 g 3,4-( 2 ) trace 29:71 h Ph trace 69:31 i Ph 2 Br :31 j :68 k PhPh trace a The reaction temp o ; p of medium: 8-9 b Ratio of dl/meso was calculated by 1 NMR c Stirred without ultrasound d p of medium: interaction 2 + l 4 + Zn B dl A meso Scheme II

4 1306 INDIAN J EM, SE B, AUGUST 2007 The following sequence of reaction appears to be a reasonable rationalization for the formation of the products 12,16 (Scheme II) The initial radical A is generated via a SET process between low valent titanium and Next two possible key coupling species B and lead to the formation of corresponding dl- and meso-products The dldiastereoselection could be explained by the initial generation of intermediate radical species whose oxygen atoms of the two ketyl radicals are linked side by side to the low valent titanium species and their aryl groups are located anti to each other to minimize the steric interaction That is: dl-pinacols are preferentially formed by an internal carboncarbon coupling of 'titanium-bridged' intermediate B which is formed readily due to the highly coordinating ability of low valent titanium species In the absence of 'titanium-bridged', the radicals of intermediate, for which steric and polar effects appear to be important, lead predominantly to the meso dimers onclusion An efficient and convenient method for the preparation of pinacols from some aromatic aldehydes and ketones by using l 4 -Zn-MeEt under ultrasound irradiation has been developed ur procedure is characterized by milder reaction conditions, shorter reaction times, higher yields, and involvement of environmentally benign solvent and available reagent In present system, when the frequency of ultrasound irradiation is 25 Kz, the ratios of l 4 /Zn was 2:4, and the p value of the medium was 8-9, the pinacols can be obtained in good yields Experimental Section Liquid aldehydes were distilled prior to use, MeEt was purified and dried before use IR spectra were recorded on a Bio-Rad FTS-40 spectrometer (KBr) MS were determined on a VG- 7070E spectrometer (EI, 70 ev) Elemental analysis was performed on a ERAEUS (N, Rapid) analyzer 1 NMR spectra were recorded on a Bruker AVANE 400 (400 Mz) spectrometer using TMS as the internal standard and Dl 3 as a solvent Sonication was performed in Shanghai Branson-QX ultrasonic cleaner (with a frequency of 25 Kz and a nominal power 250 W) and SK 250 L ultrasonic cleaner (with a frequency of 40 Kz, 59 Kz and a nominal power of 250 W; Shanghai Kudos Ultrasonic Instrument o, Ltd) The reaction flask was located in the maximum energy area in the cleaner bath, where the surface of reactants is slightly lower than the level of the water The reaction temperature was controlled by addition or removal of water from the cleaner bath General procedure A 50 ml two-neck round flask was charged with anhydrous MeEt (4 ml) and l 4 (2 mmoles) under a nitrogen atmosphere After one minute of irradiation under ultrasound, Zn powder (4 mmoles) was added in one portion When the reaction mixture turned dark-blue in colour, a solution of the desired aldehyde or ketone 1 (1 mmole) in 1 ml MeEt was added, and the p value of the reaction mixture adjusted to 8-9 with aqueous Na The mixture was irradiated for a period as indicated in Table (the reaction was monitored by TL) After the completion of the reaction, the resulting suspension was extracted with ethyl acetate (3 15 ml) The combined organic layers were washed with saturated aqueous Na 3 solution and brine, dried over anhydrous magnesium sulphate for 12 hr and filtered Ethyl acetate was evaporated off under reduced pressure to give the crude product, which was separated by column chromatography on silica ( mesh), eluted with petroleum ether or a mixture of petroleum ether and diethyl ether The authenticity of the product was established by the 1 NMR, IR, MS, or/and elemental analysis data 2a: 1 NMR: δ, 467 (2, s,, dl), 482 (2, s,, meso), (20, m, Ph-) ppm; MS: m/z (%), 214 (1), 180 (76), 167 (125), 149 (60), 107 (938), 79 (100), 77 (738); IR (KBr): cm -1 2b: 1 NMR: δ, 293 (2, s,, meso), 384 (2, s,, dl), 456 (2, s,, dl), 475 (2, s,, meso), ((16, m, Ph-) ppm; MS: m/z (%), 263 (12), 251 (16), 178 (46), 165 (46), 141 (100), 113 (238), 77 (710); IR (KBr): cm -1 2c: 1 NMR: δ, 276 (2, s,, meso), 333 (2, s,, dl), 456 (2, s,, dl), 479 (2, s,, meso), (16, m, Ph-) ppm; MS: m/z (%), 276 (14), 249 (32), 155 (100), 111 (8); IR (KBr): cm -1 2d: 1 NMR: δ, 233 (6, s, 3, dl), 238 (6, s, 3, meso), 464 (2, s,, dl), 474 (2, s,, meso), (16, m, Ph-) ppm; MS: m/z (%), 242 (12), 195 (6), 121 (100), 107 (12), 77 (13); IR (KBr): cm -1

5 Li et al: PINAL UPLING F ARMATI ALDEYDES AND KETNES e: 1 NMR: δ, 365 (6, s, 3, dl), 368 (6, s, 3, meso), 507 (2, s,, dl), 531 (2, s,, meso), (16, m, Ph-) ppm; Anal alcd for :, 7007,, 657 Found:, 7005,, 659 2f: 1 NMR: δ, 378 (6, s, 3, dl), 382 (6, s, 3, meso), 465 (2, s,, dl), 475 (2, s,, meso), (16, m, Ph-) ppm; MS: m/z (%), 276 (14), 249 (32), 155 (100), 111 (8); IR (KBr): cm -1 2g: 1 NMR: δ, 461 (2, s,, dl), 468 (2, s,, meso), 596 (4, s, 2, dl), 599 (4, s, 2 meso), (12 m, Ph-) ppm; MS: m/z (%), 302 (1), 284 (25), 268 (50), 255 (118), 151 (100), 123 (32), 93 (771), 65 (390); IR (KBr): cm -1 2h: 1 NMR: δ, 154 (6, s, 3, dl), 162 (6, s, 3, meso), 238 (2,s,, meso), 268 (2, s,, dl), (20, m, Ph-) ppm; MS: m/z (%), 225 (4), 206 (4), 181 (32), 165 (9), 121 (100), 105 (12), 77 (11), 43 (80); IR (KBr): cm -1 2i: 1 NMR: δ, 153 (4, s, 2, dl), 162 (4, s, 2 meso), 235 (2, s,, meso), 266 (2, s,, dl), (20, m, Ph-) ppm; MS: m/z (%), 303 (11), 301 (12), 240 (4), 239 (23), 201 (2), 199 (2), 123 (8), 121 (23), 105 (100), 81 (26), 43 (2); IR (KBr): cm -1 2j: 1 NMR: δ, 149 (6, s, 3, dl), 159 (6, s, 3, meso), 225 (2, s,, meso), 252 (2, s,, dl), 382 (12, d, 3 ), (16, m, Ph-) ppm; MS: m/z (%), 302 (1), 151 (100), 135 (5), 109 (4), 77 (3), 43 (60); IR (KBr): cm -1 Acknowledgements We thank the Educational Ministry of hina and the Natural Science Foundation of ebei Province ( ), hina, for financial support References 1 Robertson G M, omprehensive rganic Synthesis, edited by Trost B M, (Pergamon, New York), Seyden-Penne J, hiral Auxiliaries and Ligands in Asymmetric Synthesis (John Wiley & Sons, New York), Zhang W & Li J, J rg hem, 64, 1999, Rieke R D & Kim S, J rg hem, 63, 1998, Khurana J M & Sehgal A, hem ommun, 5, 1994, Lim J, Keum G, Kang S B, hung B Y & Kim Y, Tetrahedron Lett, 39, 1998, Nomura R, Matsuno T & Endo T, J Am hem Soc, 118, 1996, Li T Y, ui W, Liu J G, Zhao J Z & Wang Z M, hem ommun, 2000, irao T, asegawa T, Muguruma Y & Ikeda I, J rg hem, 61, 1996, Suritani T, Ito S, Shinokubo & shima K, J rg hem, 65, 2000, Basu M K, Becker F F & Banik B K, J hem Research(S), 2000, Mukaiyama T, Yoshimura T, Igarashi K & Kagayama A, Tetrahedron, 57, 2001, gawa A, Takeuchi & irao T, Tetrahedron Lett, 40, 1999, McMurry J E, hem Rev, 89, 1989, Mukaiyama T, Sato T & anna J, hem Lett, 10, 1973, lerici A & Porta, Tetrahedron Lett, 23, 1982, lerici A, lerici L & Porta, Tetrahedron Lett, 37, 1996, Li T Y, Wang L P, Zhang T, Li Y X & Wang Z M, hem J hin Univ, 21, 2000, Yamamoto Y, attori R, Miwa T, Nakagai T Y, Kubota I, Yamamoto, kamoto Y & Itoh K, J rg hem, 66, 2001, Li Y G, an Q S, Zhao J, Feng Y, Li M J & You T P, Tetrahedron: Asymmetry, 15, 2004, Li J T, hen Y X & Li T S, J hem Research(S), 2005, Li J T, Yang J & Li T S, hin J rg hem, 23 (12), 2003, Mečarová M, Toma Ś & Babiak P, hem Paper, 55, 2001, Mečarová M & Toma Ś, Green hem, 1999, (a) Mason T J, Practical Sonochemistry, (Ellis orwood Limited, New York), 1991 (b) Sprich J D & Lewandos G S, Inorg him Acta, 76 (4), 1983, Li J T, hen Y X, Yang J & Li T S, J hem Research(S), 2004, Yang J, Li J T, Zhao J L & Li T S, Synth ommun, 34 (6), 2004, 993