Nickel Chloride Promoted Glaser Coupling Reaction in Hot Water

Chinese Chemical Letters \6L. 15, No.11, pp 1295- 1298, 20041295http://www.imm.ac. cnjourmalccl.htmlNickel Chloride Promoted Glaser Coupling Reaction in Hot WaterPin Hua L, Lei WANG*, Min WANG, Jin Can YANDepartment of Chemistry, Huaibei Coal Teachers College, Huaibei 235000Abstract: A Glaser coupling reaction of terminal alkynes in the presence of nickel chloride withoutany organics and bases in hot water has been developed, which produces the correspondinghomo coupling products in good yields.Keywords: Glaser coupling reaction, terminal alkynes, nickel chloride, hot water.Diacetylene and its derivatives are very important intermediates and target molecules inbiological, polymer and material science. A classical, effective and useful method forpreparing diacetylenes was discovered by Carl Glaser in 1869, which involves a cuproussalt (CuCI) promoted oxidative homo-coupling of terminal alkynes in the presence ofoxygen, ammonia and ammonium chloride . Subsequent studies indicated that a varietyof copper salts (including cuprous and cupric salts, generally used in stoichiometricamount) are effective mediators for the coupling reaction, which is generally carried out inorganic solvents such as methanol, acetone, pyridine, methyl cellosolve, benzene andtoluene，which often pose environmental problems. In addition, the bad smell piperidine,pyridine, diethylamine and triethylamine, which are usually required in Glaser reaction,added to the environmental burden. Recently we reported that an energy efficientmodification of the Glaser coupling by using cupric chloride doped on KF/Al2O3 undersolventless reaction conditions4. However, to the best of knowledge, there is no report onthe Glaser coupling reaction promoted by nickel (I) salt.Organic reactions carried out in water have received much attention in recent years'.Unfortunately most organic compounds are poorly soluble in water at ambient temperature.Nonetheless, the unique properties of water near its critical point (T.= 374°C, P。= 221 bar)promoted the researchers to study the possibility of altermating the organic solvents by thewater in its critical point in organic synthesis. There are increasing numbers of papers,which suggested that near-critical water could be used as excellent solvent for organicreactions'Here, we wish to report a Glaser coupling reaction of terminal alkyne in the presenceof nickel chloride (30 mol %) without any organics and bases under hot water conditions.The reaction affords the corresponding coupling products in good yields.E-mail: leiwang@hbcnc.edu.cn中国煤化工MHCNM HG1296Pin HuaLI et al.R一C三C- HNiCh (30 mol%)→R-C三C-C三C一RH2O (200°C)In our optimization process investigation, phenylacetylene was chosen as a modelcompound. The results are summarized in Table 1.As shown in Table 1, the reaction temperature plays an important role in theoxidative homo-coupling reaction of terminal alkyne. It is evident that phenylacetylenecould not be completely oxidatized and subsequently coupled to form a homo- couplingproduct without any organics and bases in the presence of nickel chloride in water below170° C (entry 7, Table 1), and only a moderate yield of diacetylene was obtained at 250°C,because of the polymerization (entry 3, Table 1). A good yield of product was observedat temperature in the range of 190- -2100 C. The ratio of nickel chloride to phenylacetylenewas also examined. The results showed that when the ratio of nickel chloride tophenylacetylene was less than 0.1:1, the reaction was not completed (entries 8 and 9,Table ) and while the ratio equaled or was more than 0.2: 1, the satisfactory results wereobtained (entries 10, 11 and 1, Table 1). The effect of the reaction time on the Glasercoupling reaction indicated that the reaction was not completed when the reaction timewas less than 1 h (entry 12, Table 1). However, no increase of yield was observed whenreaction time was prolonged more than 2 h. It is surprising to find that the isolated yieldof Glaser coupling product was not increased when the reaction was carried out in thepresence of bases under hot water conditions (entries 15 and 16, Table 1). The bestreaction conditions for the oxidative coupling of phenylacetylene were found to be NiCl2(0.3 mmol), phenylacetylene (1 mmol), H2O (10 mL) at 200°C for2h.Table 1 Optimization reaction conditions for Glaser coupling ofphenylacetylene in wateraEntryNickel saltSalt amount (mol %)Temp. (°C)Time (h)Yield (%)"NiSO,3C2007:NiCh3(2505NiCl23021081NiCb1908(17070trao1(602(825(8NICI .6NCIa Reaction conditions: Phenyacetylene (1 mmo), nickel(I) salt (30 mol%), tap water (10 mL) in ahigh TIp batch reactor system. b Isolated yields. c In the presence of NaOAc (2 mmol). d In thepresence of Na2CO3 (2 mmo).中国煤化工MYHCNM HGNickel Chloride Promoted Glaser Coupling Reaction in Hot Water1297A variety of terminal alkynes were successfully coupled using the above optimizingreaction conditions. The results are listed in Scheme 1. In the presence of nickelchloride (30 mol%) without any organics and bases in water at 200 C, homo coupling ofterminal alkyne occurs smoothly to produce the desired diacetylene in moderate to goodyields. Substituent effect was also examined. The results indicated that the reaction isrelatively insensitive to the electronic nature (electron-donating or eletron-withdrawing)of subtituents on the aromatic rings.In conclusion, a reliable procedure for the synthesis of diacetylenes via a Glasercoupling reaction was developed which involves the use of nickel chloride (30 mol%) inhot water (200°C) without any organics and bases. The reaction is novel andenvironmentally friendly.Scheme 1NiCl2 (30 mol%)+ R-c三c-c=c-RH2O (200°C)R= C.Hs82%R = p-CH3C6H480g.RE0 CICH.78%R = p-FC.HA75%R =n_C_Hz688%R=n-C6H361%General procedure for the preparation of diacetylenes: Terminal alkyne (1.00 mmol)and nickel chloride (39 mg, 0.3 mmol) were added to a high T/p stainless steel autoclavereactor charged with tap water (10 mL) with stiring. The reactor was heated at 200°C for2 h. After cooling, ether (10 mLx2) was added for extracting the products. After theorganic layer was dried over anhydrous sodium sulfate, the solvents were evaporatedunder reduced pressure. The product was purified by flash chromatography.AcknowledgmentWe wish to thank the National Natural Scie nce Foundation of China (No. 20372024, 20172018), the .Excellent Scientist Foundation of Anhui Province (No. 2001040), the Scientific ResearchFoundation for the Returned Overseas Chinese Scholars, State Education Ministry China (No.2002247), and the Excellent Young Teachers Program of MOE China for support of this research.References1. (a) A. Kumar, R. A. Rhodes, J. Spychala, w. D. Wilson, D. w. Boykin, Eur. J. Med. Chem.Chim. Ther, 1995, 30, 99. (b) H. Matsunaga, M. Katano, H. Yamamoto, H. Fujito, M. Mori, K.Tukata, Chem. Pharm. Bull, 1990, 38, 3480.(c) Y.T.Park, N. Chiesel,J. Economy, Mol. Cryst.Lig Crs. Sci. Technol. Sec.A, 1994. 247,351. (d) L. Hansen, P. M. Boll, Plhyochemisty,C. Glaser, Ber, 1869, 2, 422.(a) N. Hebert, A. Beck, R. B. Lennox, G. Just,J. Org. 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On page 998, in Figure 1a one part of thecyclic voltammetry was missed. Figure 1a should be:2E-8A1E-10A0.4 -0.2 0.0 0.2 0.4E/V中国煤化工MHCNM HG