Authors: Moosun Bibi Salma Bhowon Gupta Minu Bhewa Shabneez Jhaumeer-Laulloo Sabina* Department of Chemistry, University of Mauritius * Corresponding author: sabina@uom.ac.mu
The construction of new C-C bonds is of central importance in Organic Chemistry for the assembly of complex molecular frameworks with diversified interests and applications such as: Development of new Drugs, Industrial Chemical Processes, Synthesis of Pharmaceuticals, Biologically Active Compounds, Natural product synthesis and Material chemistry.
The emergence of cross-coupling as a popular method in synthesis arises from the diversity of transition metal complexes which have been developed and used successfully as catalysts in these reactions. Among the ones used, Palladium occupy a unique position since: Facile decomposition to Pd(0). Cheaper than platinum. High recovery of palladium catalyst. Russell, M. J. H, Platinum Met. Rev. 1989 , 33, 186
Palladium phosphine complexes that have been used in C-C bond formations (Heck & Suzuki): X N O OAc Ph 3 P Ph 2 OAc PPh 2 P Pd N Pd Pd AcO PPh 3 P PPh 2 Ph 2 PPh 2 (Amotore et al, 1994) (Sabounchei & Ahmadi, 2013) (Liu et al, 2014)
Drawbacks of palladium phosphine complexes: Expensive Air sensitive. Unstable. Sometimes precipitate. Therefore the need to develop cheaper and more stable palladium-based catalysts.
The C-C coupling reactions that have been studied in this work: Heck, Suzuki and Michael Addition reactions.
[Pd 4 ( dbbs ) 4 ] ( 1 ) [Pd( dpds )Cl] ( 2 ) (dpds) 2 = o,o ’ -( N,N’ -dipicolinyldene)diazadiphenyl (dbbs) 2 = N,N'- (1,1'-dithio-bis(phenylene))bis(salicylideneimine) disulfide) In this work, palladium complexes ( 1 ) and ( 2 ) derived from Schiff Base ligands have been used as catalyst for cross coupling reactions Moosun, S. B., Bhowon, M. G., Hosten, E. C., Jhaumeer-Laulloo, S. J. Coord. Chem . 2016
It involves the coupling of an aryl, vinyl halide or sulfonate with an alkene. R catalyst R-X R' R' + base -HX The cross coupling of iodobenzene with methyl acrylate was investigated. O O I O Catalyst O + Base/Solvent Methyl cinnamate The formation of the methyl cinnamate was confirmed by 1 H NMR and GC/MS data
Fig. 1.0: 1 H NMR spectrum of methyl cinnamate 7.735 1.03 7.671 7.548 7.536 2.02 7.5 7.522 7.402 2.97 7.391 7.261 7.0 6.5 6.480 1.01 6.416 6.0 5.5 5.0 4.5 4.0 3.813 3.00 ppm
Pd paps NEt3 24h 2nd 2 1: Scan EI+ Methyl cinnamate 6.96 TIC 100 (a) 2.13e10 Octadecane 9.98 % 0 Time 5.11 5.61 6.11 6.61 7.11 7.61 8.11 8.61 9.11 9.61 10.11 10.61 11.11 11.61 12.11 PdOH Na2CO3 24 3 904 (9.985) 1: Scan EI+ 1.49e9 71.0371 (b) 57.0835 100 43.0490 85.0553 41.0226 % 29.0052 99.0662 28.0638 113.1428 127.2133 169.1787 211.2540 155.1226 197.2079 254.2430 0 m/z 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 PdOH Na2CO3 24 3 532 (6.950) 1: Scan EI+ 2.50e9 (c ) 161.8988 130.8924 100 102.9650 76.9632 160.9618 51.0078 101.9542 % 49.9227 76.0238 132.0466 104.0479 78.0471 163.0522 117.1120 63.0130 29.0052 91.0505 38.9961 133.1285 147.0474 0 m/z 25 35 45 55 65 75 85 95 105 115 125 135 145 155 165 Fig. 2.0: (a) GC chromatogram of methyl cinnamate and octadecane; (b) Mass spectrum of octadecane; (c) Mass spectrum of methyl cinnamate .
The reaction conditions were systematically optimized in the standard reaction of iodobenzene with methyl acrylate using catalyst 1 . The parameters that were being investigated are: Time, Solvent, Base Catalyst loading.
Optimization of reaction conditions between iodobenzene and methyl acrylate: 120 °C, 1 , DMF (10 mL), Na 2 CO 3. % Yield was determined by GC-MS. Octadecane was used as internal standard. Time Effect Time (h) % Yield 0 0 100 % Yield 5 0 24 99 0 48 84 0 5 24 69 70 48 69 Time (h) Time Effect: Maximum conversion was obtained at 24h. A steady decrease in yield was observed after 24h. Catalyst loading Effect % Yield 100 Catalyst (mMol) % Yield 0 0.0025 74 0.0025 0.0052 0.0052 96 0.0075 Catalyst (mM ol) 0.0075 99 Catalyst loading effect: > 99 % conversion achieved with 0.0075 mMol.
Base Effect Base % Yield 100 % Yield Na 2 CO 3 96 K 2 CO 3 99 0 Et 3 N 97 Na2CO3 K2CO3 Et3N NaOAc 25 NaOAc Bases Base effect: Both organic and inorganic bases were found to be very efficient except NaOAc. K 2 CO 3 was used for further studies. Solvent effect Solvent % Yield 100 % Yield DMF 96 DMA 87 0 DMF CH 3 CN 0 DMA CH3CN Toluene Toluene 0 Solvent Solvent effect: CH 3 CN and toluene were inefficient. DMF was used for further reactions.
The scope of the reaction was further evaluated using various aryl halides and catalysts. Evaluation of halide groups and catalyst in Heck reactions O O X O O Catalyst + K 2 CO 3 /DMF 120 °C Entry X Catalyst % Conversion 1 I 1 > 99 2 Cl 1 Trace 3 Br 1 Trace 4 I - - 5 I PdCl 2 3 6 I 2 98 Aryl halide: 3.0 mmol; methyl acrylate: 8.32 mmol, catalyst: 0.0052 mmol, base: 4.5 mmol; time: 24 h. Octadecane was used as internal standard. % conversion was determined by GC-MS as an average of two injections . With chloro and bromo benzene, trace amount of product was obtained. With iodo benzene- in absence of catalyst, no Heck product formed while with PdCl 2 only, trace amount obtained. Complexes 1 and 2 showed comparable yields,
Suzuki reaction is the cross-coupling of an aryl or vinyl boronic acid with aryl or vinyl halide or triflate and allows the synthesis of conjugated olefins, styrenes, and biphenyls. Preliminary studies were carried out using complexes 1 and 2 and further investigation is still under process. Catalyst + X B(OH) 2 Na 2 CO 3 X = I or Br iso-propanol Biphenyl
Biphenyl std 2: Scan EI+ TIC 10.42 100 6.17e8 % 34 Biphenyl std 635 (10.410) 2: Scan EI+ 0 Time 7.43e7 154.1895 5.01 7.01 9.01 11.01 13.01 15.01 17.01 19.01 21.01 23.01 25.01 27.01 29.01 100 153.1797 50.9757 % 75.9908 38.8972 152.1698 63.0512 77.0027 73.9670 26.8882 37.9568 61.9667 151.2320 86.9033 155.1272 102.0024 115.0740 78.0145 128.1411 65.0033 39.9099 139.1832 31.9526 0 m/z 21 31 41 51 61 71 81 91 101 111 121 131 141 151 161 Fig. 3.0: (a) GC chromatogram of biphenyl; (b) Mass spectrum of biphenyl.
Suzuki reactions were carried out for 6 h under refluxing conditions with iodo and bromo as aryl halides. % conversion was determined after isolation of products. Table 2: Evaluation of halide groups and catalyst in Suzuki reactions Entry X Catalyst % Conversion 1 I 1 97 2 Br 1 60 3 I 2 99 4 Br 2 64 Aryl halide: 0.01 mol; acid: 0.01 mol, catalyst: 0.1 mmol, base: 0.2 M; time: 6 h. Moderate to excellent yields were obtained. Both catalysts were very efficient since high % conversion were obtained (entry 1 and 3). The bond strength of C-X influences the yield of the reaction.
It involves a nucleophilic attack of carbanions to α,β -unsaturated carbonyl compounds under basic (for deprotonation of donor) or acidic medium (activation of acceptor) in organic solvents. In the base catalysed reactions, the donor is first deprotonated forming an enolate anion which then reacts with the acceptor in a 1,4- fashion . O O K 2 CO 3 CH 2 (CO 2 CH 2 CH 3 ) 2 + Catalyst CO 2 CH 2 CH 3 THF CO 2 CH 2 CH 3
6.87e8 160.0300 28.8714 100 161.0384 27.8542 % 133.0812 55.0606 82.9923 M + 113.0327 95.0584 38.9640 197.0409 68.0215 123.0592 141.0818 105.0223 185.0180 198.0487 214.0296 168.0245 241.9596 0 m/z 24 34 44 54 64 74 84 94 104 114 124 134 144 154 164 174 184 194 204 214 224 234 244 Fig. 4.0: Mass spectrum of Michael adduct
The use of catalysts of 1 and 2 in the Michael reactions of cyclopentenones with diethymalonates in THF at different temperatures (24-60 ° C) did not gave the desired product as confirmed by the mass spectrum below. 1.82e9 27.5728 132.0902 100 83.0127 28.2240 55.1249 99.1138 133.1001 82.0739 % 39.0742 127.1129 157.0419 183.0641 68.9995 153.0043 122.2793 26.1257 158.0513 184.0731 214.1203 251.8648 0 m/z 18 28 38 48 58 68 78 88 98 108 118 128 138 148 158 168 178 188 198 208 218 228 238 248 258 Fig. 5.0: Mass spectrum of Michael adduct using catalysts 1 and 2
Both palladium complexes were found to be efficient catalysts in promoting the Heck and Suzuki reactions. The products were obtained in excellent yields even at a very low catalyst loading. The yields of the product were highly dependent on parameters such as time, solvent, base and substrate. Both catalysts gave comparable yields, however catalyst 2 was better than 1 , considering its lower palladium content. The complexes were inefficient as catalysts in Michael addition reactions.
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