Method for the Preparation of Iodoalkanes

Abstract

The present invention relates to an atom economic procedure of preparing iodoalkanes by hydroiodination of alkenes. In particular the present method features the generation of anhydrous hydrogen iodide from atomic hydrogen and iodine in situ by using transition metal precursor and phosphine ligandcatalyst.

Claims

1. A method of producing iodoalkanes comprising hydroiodinating alkene with hydrogen and iodine with a transition metal precursor and a phosphine ligand as catalyst, wherein said metal precursor is selected from the group consisting of rhodium, iridium, and ruthenium precursor.

2. The method according to claim 1, further comprising converting the hydrogen and iodine into anhydrous hydrogen iodide.

3. The method according to claim 1 wherein said hydroiodinating step is performed in situ and the hydrogen and iodine are atomic hydrogen and iodine.

4. The method according to claim 1 wherein the transition metal precursor is selected from the group consisting of Rh(COD).sub.2BF.sub.4, Rh(CO).sub.2(C.sub.5H.sub.7O.sub.2), [Rh(COD)Cl].sub.2, Rh(COD).sub.2SbF.sub.6, Rh(COD).sub.2OTf, C.sub.14H.sub.16Cl.sub.2Rh.sub.2, [Ir(COD)Cl].sub.2, and Ru(COD)Cl.sub.2.

5. The method according to claim 1 wherein the phosphine ligand is selected from the group consisting of ()-Binap, PPH.sub.3, DPPE, DPPB, XANTPHOS and tricyclohexyphosphine.

6. The method according to claim 1 wherein the method is performed under a pressure of 2-6Mpa and at 0-40 C.

7. The method according to claim 1 wherein the alkene, transition metal precursor and phosphine ligand are dissolved in a solvent.

8. The method according to claim 7 wherein the solvent is selected from the group consisting of DCE, toluene, and DCM.

9. The method according to claim 1, wherein the hydroiodinating step is ##STR00039##

10. The method according to claim 1, wherein the hydroiodinating step is ##STR00040##

11. The method according to claim 1, wherein the hydroiodinating step comprises mixing the transition metal precursor, the phosphine ligand, a solvent to produce a first solution; stirring the first solution at room temperature to produce a second solution; adding iodine and alkene to the second solution to produce a reaction mixture; autoclaving the reaction mixture; stirring the reaction mixture at room temperature under a pressure of 4 Mpa; removing the solvent to produce a residue; and purifying the residue to obtain the iodoalkane.

12. The method according to claim 1, wherein the ratio of alkene to iodine to transition metal precursor to phosphine ligand is 1:1:0.05:0.065.

13. The method according to claim 1, wherein the transition metal precursor is 0.01%-5% of the reaction mixture and the phosphine ligand is 0.01%-6% of the reaction mixture.

14. The method according to claim 11, wherein the reaction mixture is stirred for 6 to 96 hours.

15. The method according to claim 6, wherein method is performed under a pressure of 4 Mpa and at 20-25 C.

16. An apparatus for producing iodoalkanes using the method according to claim 1.

Description

DETAILED DESCRIPTION

[0031] The present invention is not to be limited in scope by any of the specific embodiments described herein. The following embodiments are presented for exemplification only.

[0032] Without wishing to be bound by theory, the inventors have discovered through their trials, experimentations and research that to accomplish the task of an atom economic procedure of preparing iodoalkanes by hydroiodination of alkenes.

[0033] The hydrogenation reaction of alkenes, represents an example of hydrogen activation by transition metal catalyst and is the most wildly used reaction in organic chemistry industry. The reaction mechanism for hydrogenation reactions was known as Horiuti-Polanyi mechanism, which describes hydrogen molecule dissociation followed by the sequential addition of atomic hydrogen to the alkenes. The inventors show in the present application using iodine as an atomic hydrogen acceptor result in generation of anhydrous hydrogen iodide. Herein, the inventors describe a new preparation method for iodoalkanes via the hydroiodination reactions of alkenes by anhydrous hydrogen iodide generated in situ from molecular hydrogen catalyzed by a transition metal precursor-ligand catalyst. The present invention provides a method of producing iodoalkane with a product yield of at least 70%. In some embodiment, the present method results in at least 80% yield of iodoalkane. In some embodiment, the product yield of iodoalkane by the method of the present invention is over 90%.

[0034] Initial trials are carried out with a complex of Rh(COD)BF.sub.4 and PPh.sub.3 as catalyst, DCE as solvent, and performed under a hydrogen atmosphere of 4 MPa. The inventors have observed the fading of puce iodine solution, and finally a light yellow solution is obtained and give the addition product 1-iodo-1-phenylethane in 75% yield in 4 hours (Table 1, entry 1). Referring to Table 1, to improve the reaction yield, alternative phosphine ligands are screened. The ratio of alkene to iodine to metal precursor to ligand of the present method is 1:1:0.05:0.065. Reaction conditions of Table 1: styrene (0.2 mmol), styrene/I.sub.2/Metal/Ligand (1:1:0.05:0.065), in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4 Mpa for 48 hours. The results show phosphine ligand promotes hydroiodination reaction. Phosphine ligands suitable for use in the method of the present invention includes, but are not limited to, ()-Binap, PPH.sub.3, DPPE, DPPB, XANTPHOS and tricyclohexyphosphine, In an embodiment, the phosphine ligand of the present invention is ()-Binap. Using ()-Binap as the ligand, various transition metal precursors including rhodium, palladium, iridium, and ruthenium precursors are next tested. The transition metal precursor of the present invention includes, but are not limited to, Rh(COD).sub.2BF.sub.4, Rh(CO).sub.2(C.sub.5H.sub.7O.sub.2), [Rh(COD)Cl].sub.2, Rh(COD).sub.2SbF.sub.6, Rh(COD).sub.2OTf, C.sub.14H.sub.16Cl.sub.2Rh.sub.2, [Ir(COD)Cl].sub.2, and Ru(COD)Cl.sub.2. The results indicate that most of tested transition metal catalysts promote hydroiodination reaction, and Rh(COD).sub.2BF.sub.4 is the preferred embodiment (entry 2, 84% yield). However, RhCl.sub.33H.sub.2O, [Rh(C.sub.5Me.sub.5)Cl.sub.2].sub.2 and palladium catalysts show little activities (entry 10-11, 15-16), The hydroiodination reaction is shown below:

##STR00003##

TABLE-US-00001 TABLE 1 Product yield of iodoalkane from different combination of ligands and transition-metal precursors. Reaction conditions: styrene (0.2 mmol), styrene/I.sub.2/Metal/Ligand (1:1:0.05:0.065), in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4 Mpa for 48 hours. Entry Metal precursor Ligand Yield/%.sup.[a] 1 Rh(COD).sub.2BF.sub.4 PPh.sub.3 75 2 Rh(COD).sub.2BF.sub.4 ()-Binap 84 3 Rh(COD).sub.2BF.sub.4 dppe 80 4 Rh(COD).sub.2BF.sub.4 dppb 72 5 Rh(COD).sub.2BF.sub.4 dppf 79 6 Rh(COD).sub.2BF.sub.4 XANTPHOS 70 7 Rh(COD).sub.2BF.sub.4 Tricyclohexylphosphine 77 8 Rh(CO).sub.2(C.sub.5H.sub.7O.sub.2) ()-Binap 61 9 [Rh(COD)Cl].sub.2 ()-Binap 53 10 RhCl.sub.33H.sub.2O ()-Binap trace 11 [Rh(C.sub.5Me.sub.5)Cl.sub.2].sub.2 ()-Binap N.R 12 Rh(COD).sub.2SbF.sub.6 ()-Binap 72 13 Rh(COD).sub.2OTf ()-Binap 47 14 C.sub.14H.sub.16Cl.sub.2Rh.sub.2 ()-Binap 51 15 Pd(OAC).sub.2 ()-Binap trace 16 [PdCl(C.sub.3H.sub.5)].sub.2 ()-Binap N.R 17 [Ir(COD)Cl].sub.2 ()-Binap 58 18 Ru(COD)Cl.sub.2 ()-Binap 56 .sup.[a]Isolated Yield. Note: COD = 1,5-cyclooctadiene; [PdCl(C.sub.3H.sub.5)].sub.2 = allylpalladium(II) chloride dimer; [Rh(C.sub.5Me.sub.5)Cl.sub.2].sub.2 = pentamethylcyclo-pentadienylrhodium(III) chloride dimer. Ligands [00004][00005][00006][00007][00008][00009][00010]

[0035] The reaction solvent, temperature, and pressure are next investigated. The results are compiled in Table 2. The solvent test results show solvents of the hydroiodination reaction of the present invention are DCE, toluene, and DCM (entry 1-3). Other solvents, including DMA, DMF, MTBE, i-PrOH, and DME are not suitable solvent (entry 4-8). Hydroiodination of the present method is performed in 0-40 C. and under pressure ranges from 2-6 MPa. In another embodiment, the present method is performed at 20-25 C. The inventors of the present application has found that hydroiodination outside the temperatures and pressures of the present method reduce the product yield to lower than 80%. The following temperature and pressure experiments indicate that the best reaction result is obtained at room temperature and under a pressure of 4 MPa. Increasing the reaction temperature or pressure of hydrogen proved detrimental to this result (entry 9-13).

##STR00011##

TABLE-US-00002 TABLE 2 Product yield of iodoalkane under different temperatures and pressures. Reaction conditions: styrene (0.2 mmol), styrene/I.sub.2/ Rh(COD).sub.2BF.sub.4/()-Binap (1:1:0.05:0.065), in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4 Mpa for 48 hours. Entry Solvent Temperature( C.) Pressure(MPa) Yield(%).sup.[a] 1 DCE r.t. 4 84 2 Toluene r.t. 4 88 3 DCM r.t. 4 50 4 DMA r.t. 4 N.R 5 DMF r.t. 4 N.R 6 MTBE r.t. 4 N.R 7 i-PrOH r.t. 4 N.R 8 DME r.t. 4 trace 9 Toluene 0 4 82 10 Toluene 40 4 75 11 Toluene r.t. 2 68 12 Toluene r.t. 3 73 13 Toluene r.t. 6 83 .sup.[a]Isolated Yield.

[0036] With the optimized reaction conditions in hand (5 mol % of Rh(COD).sub.2BF.sub.4, 6 mol % of Binap, toluene as solvent and perform under 4 MPa at room temperature), the scope and limitations for this hydroiodination reaction of various alkenes is investigated. The results are compiled in Table 3. Table 3 shows the product yield of one embodiment of the present method, styrene (0.2 mmol) is hydroiodinated in the following ratios: 1:1:0.05:0.065 of styrene/I.sub.2/Rh(COD).sub.2BF.sub.4/()-Binap, in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4 Mpa for indicated period of time. Most of the alkenes, inhydroiodination reaction, proceed smoothly to afford corresponding iodoalkanes as Markovnikov addition products. Notably, high reaction yields are achieved by halogenated styrene (entry 2-9), diphenylethene (entry 15, 16) and linear terminal alkenes (entry 19-21). However, trimethyl-2-vinylbenzene gives no product probably due to steric hindrance (entry 12). Electron donating group substituted alkenes such as 1-methyl-4-vinylbenzene, 1-methoxy-4-vinylbenzene, vinylcyclohexane and oct-1-ene are less active in hydroiodination, especially for para-methoxyl-styrene (entry 10, 13, 17 and 23). 1,2-Dihydronaphthalene and 1,4-dihydronaphthalene are also not suitable for present reaction (entry 24 and 25).

##STR00012##

TABLE-US-00003 TABLE 3 Product yield of iodoalkane prepared from different alkenes. Reaction conditions: styrene (0.2 mmol), styrene/I.sub.2/Rh(COD).sub.2BF.sub.4/()-Binap (1:1:0.05:0.065), in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4Mpa for indicated period of time. Entry Alkenes Time (h) Yield(%).sup.[a] 1 [00013] 24 88 2 [00014] 24 92 3 [00015] 24 90 4 [00016] 12 99 5 [00017] 6 99 6 [00018] 6 99 7 [00019] 6 99 8 [00020] 6 99 9 [00021] 6 98 10 [00022] 48 52 11 [00023] 96 83 12 [00024] 96 TRACE 13 [00025] 96 NR 14 [00026] 24 81 15 [00027] 12 99 16 [00028] 72 99 17 [00029] 72 66 18 [00030] 24 76 19 [00031] 6 99 20 [00032] 24 96 21 [00033] 24 99 22 [00034] 72 91 23 [00035] 72 55 24 [00036] 96 Trace 25 [00037] 96 Trace .sup.[a]Isolated Yield.

[0037] The present invention provides a high atom economic method of hydroiodination for the preparation of iodoalkanes from alkenes. As the amount of catalyst is an essential element in chemistry industry, the inventors next explore the utility of present reaction with different catalyst loadings (Table 4). When the catalyst loading decreases to 0.1% Rh(COD).sub.2BF.sub.4 and 0.12% ()-Binap, the hydroiodination remains proceed in a high yield. (entry3, 94%yield) Further decreasing of catalyst loading decreases the reaction yield dramatically (entry 4-6). Apparently, no reaction takes place in the absence of catalyst (entry 7). Therefore, the present hydroiodination can be realized in high yield (>90%) by an extremely low catalyst loading of 0.1% or down to 0.01% accrodingly to the present method. In one embodiment, at least 0.01% of metal precursor and 0.012% of ligand are used in the present method to result over 80% product yield.

##STR00038##

TABLE-US-00004 TABLE 4 Catalyst loading of hydroiodination reaction. Reaction conditions: 1-chloro-2-vinylbenzene (0.2 mmol), 1-chloro-2-vinylbenzene/I.sub.2/ Rh(COD).sub.2BF.sub.4/()-Binap (1:1:0.05:0.065), in DME (2 mL) at room temperature under H.sub.2 with a pressure of 4 Mpa. Entry Metal Ligand Yield/%.sup.[a] 1 5% 6% 99 2 1% 1.2%.sup. 96 3 0.1%.sup. 0.12% 94 4 0.01% 0.012% 86 5 0.001% 0.0012% 62 6 0.0001% 0.00012% Trace 7 0% 0% N.R .sup.[a]Isolated Yield.

[0038] In conclusion, the present application provides the first catalytic preparing method of iodoalkane from anhydrous hydrogen iodide using iodine and hydrogen. The method of the present application synthesizing iodoalkanes from hydroiodination of aryl and alkyl alkenes results in >80% high yield. Notably, the present method has provided an atom economic procedure for preparing anhydrous hydrogen iodide, which offers a promising future for its further utilization in other hydrogen iodide participating reactions. One embodiment of rhodium catalyzed hydroiodination reactions of alkenes of the present invention:

[0039] Rh(COD).sub.2BF.sub.4 (4.1 mg, 0.01 mmol), ()-Binap (8.1 mg, 0.013 mmol), and 1.0 mL toluene are added to a tube under argon atmosphere. The resulting solution is stirred at room temperature for 30 min. Then iodine (50.8 mg, 0.2 mmol) and alkene (0.2 mmol) dissolved in toluene (2 ml) are added, and the tube is subjected to a mini autoclave. After the hydrogen replacement, the reaction mixture is stirred at room temperature for 48 hours under a pressure of 4Mpa. Then toluene solvent is removed by vacuum evaporation, and the residue is purified by silica gel column chromatography to obtain the iodoalkane as desired product.

INDUSTRIAL APPLICATION

[0040] The present invention relates to an atom economic procedure of preparing iodoalkanes by hydroiodination of alkenes. In particular the present method features the generation of anhydrous hydrogen iodide from atomic hydrogen and iodine in situ by using transition metal precursor and phosphine ligandas catalyst.