Assorted types of reactions were completed to first create and so utilize Jacobsen’s accelerator in the asymmetric epoxidation of an unknown olefine with bleach in the research lab. The chiral epoxide synthesized was so characterized with GC/MS and NMR. With this information the unknown olefine was able to be identified as 4-chlorostyrene. Introduction
Organisms have evolved with mechanisms that use specific enantiomorphs of molecules. If the chirality of the molecules is wrong. they may non be utilised or may even ache the being. For this ground a method to make chiral molecules is really of import and for this ground we study asymmetric synthesis. One method in which a chiral epoxide can be synthesized is through the usage of a Jacobsen-type accelerator. In order to synthesise Jacobsen’s accelerator. Jacobsen’s ligand must be created foremost which requires the usage of 3. 5-di-tert-butyl-salicylaldehyde. There are many methods by which this salicylaldehyde can be synthesized but one method with a comparatively high output starts with 2. 4-di-tert-butylphenol. The reaction strategy is shown below in Figure 1.
Figure 1: ( 1 ) 2. 4-di-tert-butylphenol. ( 2 ) 2. 4-di-tert-butyl-6-hydroxymethylphenol. ( 3 ) 3. 5-di-tert-butyl-salicylaldehyde shown above. In this reaction ( 1 ) was reacted with formaldehyde using a Lederer-Mannase reaction giving ( 2 ) with a good output. This compound was so oxidized in order to organize ( 3 ) . One oxidizing agent which could be used is sodium hypochlorite ( bleach ) with stage transportation accelerator. This method of synthesising the salicylaldehyde is advantageous because it has a really high output of 88 % . 1 It besides uses many of the techniques that undergraduate pupils have already learned such as vacuity filtration. drying over anhydrous Na sulphate. and recrystallization. An alternate method in which one can synthesise chiral epoxides is through the usage of a fructose-derived accelerator alternatively of the Jacobsen’s accelerator. The dioxirane that is formed in the derivation performs the oxidization. The reaction strategy for making the fruit sugar derived accelerator is shown below in Figure 2.
Figure 2: ( 4 ) D-fructose. ( 5 ) bis-ketal intoxicant. ( 6 ) fructose-derived accelerator
The first measure in synthesising the accelerator is ketalization. which protects four of the five hydroxyl groups on the fruit sugar. This ketalization allows for good stereoselectivity holding an enantiomeric surplus value runing from 85-97 % . 2 The 2nd and concluding measure is the oxidization of the unprotected hydroxyl group utilizing PCC. an oxidizing agent. The freshly created accelerator can so be converted into a dioxirane. as shown in Figure 3. in the presence of K peroxomonosulfate. The dioxirane formed performs the epoxidation of the olefine.
Figure 3: Catalyst – top center. dioxirane – underside center. olefine and epoxide – right side.
Though the output of this reaction is high it utilizes percholoric acid and PCC which are potentially risky reagents. Other than that. the reaction allows the pupil to utilize such techniques as recrystallization to sublimate merchandises. column chromatography to divide merchandises from reactants. and allows pupils to suggest designs of other accelerators that could be used using different sugars and expected outputs and enantiomeric surpluss. Results/Discussion
Resolution:
In order to undergo asymmetric synthesis. the reactants must be as optically pure as possible to bring forth a merchandise with high optical pureness. but because a individual enantiomorph of 1. 2-diaminocyclohexane is much more expensive and impractical for undergraduate research labs. a mixture of trans-cis isomers is used. Therefore a declaration measure is required to bring forth higher optical pureness. The job with utilizing simple stairss such as recrystallization is that enantiomorphs have the same physical belongingss. To besiege this job. diastereomeric tartrate salts are synthesized by blending with ( L ) – ( + ) -tartaric acid. These diastereomers happen to hold big adequate differences in their solubilities to be able to divide them via recrystallization. This difference in solubility is likely due to stronger ionic interactions between the tartaric acid and the diammonium with the fiting constellation.
When running the experiment it is of import to add the diamine to the tartaric acid in orderly signifier because the reaction is exothermal and the heat could impede the reaction. Glacial acetic acid is so added to take down the pH of the solution to protonate the diamine leting it to precipitate and organize crystals to be isolated. The literature output in the reaction is 30 % of the ( R. R ) -diammonium salt with pure diamine with a runing point scope from 205-207°C and an optical rotary motion of -12. 5° . 3 The declaration reaction strategy is shown below in Figure 4.
Figure 4: 1. 2-Diaminocyclohexane with the add-on of ( L ) – ( + ) -tartaric acid reacts to make a four diastereomers but merely the ( 1R. 2R ) -diammonium- ( 2R. 3R ) -tartrate salt signifier crystals in cold H2O.
In the experiment a output of 28 % of the mark salt was resolved. This output is really good when compared to the theoretical upper limit of 30 % . The little loss of merchandise may be due to pipet mistake or residue left in Hirsch funnel. It besides may be because the full merchandise had non precipitated out before being vacuity filtrated. The ascertained thaw point had a broader scope of 200-206°C which may hold been due to drosss in the sample. Finally an optical rotary motion of -12. 6 was found with a 1 % concentration of the salt in distilled H2O. This optical rotary motion is really near to the literature value demoing that the declaration had really high enantiomorph surplus and had been successful. Jacobsen’s Ligand Synthesis
The synthesis of Jacobsen’s ligand is a preliminary measure towards making the accelerator needed for epoxidation. The tartrate salt is dissolved in a mixture of K carbonate and H2O in order to deprotonate the ammonium map. Because there are two ammonium maps. two equivalents of the K carbonate are needed. Adding ethanol lowers the mutual opposition of the solution which. in bend. increases the solubility of the salicylaldehyde leting it to remain in solution and react with the diamine to organize the ligand. Solubility of the ligand can be decreased by adding H2O to let the ligand to precipitate and organize crystals when cooled to be isolated via vacuity filtration. Crude ligand merchandise is dissolved in a solvent mixture of ethyl ethanoate and hexane because it does non fade out moderately in either solvent entirely. The mixture of dissolvers allows for a better solubility curve which will increase the pureness of the concluding ligand merchandise. This procedure yields about 100 % of the mark merchandise. 4 Jacobsen’s ligand has a runing point of 202-203°C. 5 It besides has an optical rotary motion of -315 ± 15 in methylene chloride. 6 The reaction strategy is shown below in Figure 5.
Figure 5: tartrate salt ( left ) is reacted with 2 equivalents of K carbonate to let go of the diamine ( centre ) which can so assail the carbonyl of the aldehyde to make Jacobsen’s ligand ( right ) .
The experimental output of the ligand was 65 % a instead low output when compared to the literature value of about 100 % . which may hold been due to loss when seeking to pull out the merchandise from the unit of ammunition underside flask and the Hirsch funnel after vacuity filtration. Besides there may hold been some unreacted aldehyde which did non remain in solution to respond with the tartrate salt imputing to the low output. Another ground for the low output may hold been from all the merchandise non crystallising prior to hoover filtration. The ascertained thaw point was 200-205°C which is really near to the literature value of 202-203°C. which provides some grounds that the merchandise obtained was pure. The broader scope may hold been due to several drosss left in the merchandise such as unreacted tartrate salt or salicylaldehyde. However the optical rotary motion of the merchandise was -328° which is within the mistake of the literature value. Jacobsen’s Catalyst Synthesis
After the ligand was synthesized. the accelerator for epoxidation could eventually be made. Manganese ( II ) ethanoate is crushed in order to increase the surface country of the atoms leting for more oxidization to happen faster by maximising the figure of hits. The Mn ( II ) ion forms a chelate with the two O atoms of the ligand and coordinates the imine N atoms every bit good to organize a Mn ( II ) composite. After this composite is formed O is introduced into the system via an air watercourse through a glass tubing in order to oxidise the Mn ( II ) to manganese ( III ) in presence of Li chloride and the brownish Jacobsen’s accelerator is formed. The reaction advancement is monitored by TLC. The mutual opposition of the solution is lowered by adding high-boiling crude oil quintessence and vaporizing extra dissolver leting the accelerator to precipitate and be collected. Figure 6: Jacobsen’s ligand ( left ) reacted with manganese ( II ) ethanoate in H2O to organize a coordination composite ( center ) which is oxidized via an air watercourse and add-on of Li chloride ( right ) .
In the research lab a 41 % output was observed which was instead far from the literature value of 70-85 % . 7 Loss of merchandise could be due to leting the accelerator to sit in the high boiling crude oil quintessence over the weekend because of deficiency of clip to complete it in one research lab period. Besides the ligand was non wholly used up as some xanthous solid could still be seen in the accelerator solution after halting the reflux. One job experienced in the lab was the solvent being boiled off excessively rapidly during the reflux. After adding ethyl alcohol. within five proceedingss the solvent degree would drop significantly. In order to relieve this job the heat was turned down to make a gentler furuncle and more ethyl alcohol was added. In the TLC a really weak topographic point near the dissolver forepart was still seen after halting the reaction meaning that unreacted ligand was still present. A dark topographic point near the start line signified the presence of accelerator. The runing point scope of the merchandise obtained was 327-330°C which is near to the literature value of 330-332°C. Epoxidation of an Alkene
Jacobsen’s accelerator was used to catalyse the epoxidation of an unknown olefine with a bleach solution that was buffered in order to keep a pH of 9. 5-11. 5. This pH minimizes the sum of side reactions that could happen such as hydrolysis of the epoxide. After the reaction is completed it is extracted and purified with brassy chromatography to divide the epoxide from unreacted olefine and other side merchandises.
Figure 7: 4-chlorostyrene ( left ) is reacted with Na hypochlorite in the presence of Jacobsen’s accelerator to make 3-chlorostyrene oxide ( right ) In the lab a output of 18. 9 % epoxide was accomplished. Which is rather close to the literature value of 22 % . 8 A higher output could hold been given if the temperature was higher nevertheless the mixture would so be more susceptible to side reactions which would most likely lessening the pureness of the merchandise. The enantiomeric surplus calculated utilizing the GC of the epoxide sample was found to be 41. 4 % . The TLC used to supervise the reaction was a 1:7 mixture of ethyl ethanoate: hexane. giving an Rf value of around. 5 for the epoxide and. 8 for the olefine. Both of these compounds were seeable under UV-light. Another set with an Rf of about. 3 was besides visualized under UV-light which may hold been due to some side merchandise such as a glycol formed by the debasement of the epoxide. Experimental
Resolution
In the declaration measure of the experiment 2. 24 g ( 0. 01 mol ) of ( L ) – ( + ) -tartaric acid was dissolved in 15 milliliter of distilled H2O with a stir saloon in a 150 milliliter beaker. 6 milliliter ( 0. 05 mol ) of a 60:40 ( trans: Commonwealth of Independent States ) mixture of 1. 2-Diaminocyclohexane was so easy added while stirring the system. After 10 proceedingss. 5 mL glacial acetic acid was added. After a few more proceedingss the solution was placed in an ice bath for 30 proceedingss. Solid was collected by vacuity filtration and washed with 5 milliliters ice-cold distilled H2O twice and 5 mL ice-cold methyl alcohol twice. The white merchandise was dissolved once more with 100 milliliters hot H2O and allowed to make room temperature before puting in an ice-bath. This experiment produced 3. 77 g of tartrate salt or a 28 % output. The ascertained thaw point obtained was 200-206°C and the optical rotary motion was found to be -12. 6° with a concentration of 1. 008 % . The tartrate salt appeared to be all right. white. shiny. odourless crystals. Ligand Synthesis
In the ligand synthesis measure of the experiment 0. 32 g ( 0. 001 mol ) tartrate salt. 4 milliliter ( 0. 22 mol ) H2O. and. 33 g ( 0. 002 mol ) K2CO3 were assorted in a 100 milliliter unit of ammunition underside flask. 4 milliliter of 95 % ethyl alcohol was added and the solution was refluxed. While stirring. 0. 56 g ( 0. 002 mol ) 3. 5-di-tert-butyl-salicylaldehyde was assorted with 3 milliliters of 95 % ethyl alcohol in a warm H2O bath to assist the aldehyde dissolve. This solution was so added to the unit of ammunition underside flask and rinsed with 95 % ethyl alcohol via a Pasteur pipette. After refluxing for 45 proceedingss. 3 mL H2O was added and so the solution was taken off the heat and allowed to chill to room temperature. After making room temperature. the solution was placed in an ice bath and after 10 proceedingss. the crystals were collected via vacuity filtration rinsing with 3 milliliters ice-cold ethyl alcohol two times. The solid was extracted and dissolved with 15 milliliters of a mixture of ethyl ethanoate: hexane ( 1:1 ) and washed with 15 milliliters H2O twice and 30 milliliter saturated sodium chloride. The xanthous solution was so dried over anhydrous Na sulphate for 10 proceedingss and so the dissolver was removed utilizing the rotary evaporator. This experiment produced 0. 4211 g Jacobsen’s ligand or a output of 65 % . a runing point of 200-205°C. and an optical rotary motion of -328° . The ligand appeared to be a bright xanthous solid. Catalyst Synthesis
In the accelerator synthesis measure 0. 40 g ( 0. 0007 mol ) of ligand was dissolved in 15 milliliter ethyl alcohol and refluxed for 10 proceedingss in a two-necked unit of ammunition underside flask with a water-jacketed capacitor attached. 0. 30 g ( 0. 001 mol ) of crushed Mn ( II ) ethanoate was added and the solution was refluxed for an extra 20 proceedingss. Air was so introduced into the system via a glass tubing through an arranger. 15 milliliter ethyl alcohol was added as the solution degree became excessively low. As the xanthous ligand continued to vanish the solution became a darker shadiness of brown. The reaction was monitored by TLC utilizing a prepared diluted solution of the ligand in ethyl ethanoate: hexane ( 1:4 ) mixture and a little sum of diluted reaction mixture. Once the ligand topographic point disappeared from the reaction mixture. 0. 10 g ( 0. 002 mol ) Li chloride was added and the mixture was refluxed for 15 more proceedingss.
Then the flask was removed from the heat and the extra dissolver was removed with the rotary evaporator. The residue was dissolved in ethyl ethanoate and washed with 10 milliliters H2O twice and 20 milliliter saturated sodium chloride. This mixture was dried over anhydrous Na sulphate for 10 proceedingss before being pull outing from the drying agent and adding 20 mL high-boiling crude oil quintessence. Solvent removed once more with rotary evaporator go forthing a brown slurry. Because of clip restraints this slurry was left for a few yearss before being vacuity filtrated and obtaining the solid precipitate. This experiment produced 0. 19 g of Jacobsen’s accelerator or a 41 % output with a runing point of 327-330°C. The accelerator appeared to be a brownish solid. Epoxidation of an Alkene
In the epoxidation measure a buffered bleach solution was created by blending 12. 5 milliliter ( 0. 19 mol ) Na hypochlorite. one bead of 1M NaOH. and 10 milliliter of 0. 05M Na2HPO4. Another solution with 0. 5188g ( 0. 004 mol ) 4-chlorostyrene. 0. 1882g of Jacobsen’s accelerator. and 5 milliliter ethyl ethanoate was so created and added to the buffered bleach solution. The flask was sealed with Parafilm and stirred smartly. After about an hr the reaction was monitored by TLC utilizing a 1:7 mixture of ethyl ethanoate: hexane to find when the 4-chlorostyrene was wholly used up. Once the reactant was wholly consumed. 50 milliliter of hexane was added to work-up the mixture. The two stages were so separated and the organic bed was extracted twice with 10 milliliters of concentrated NaCl. The organic infusion was so dried over anhydrous Na sulphate. Once dry. it was transferred to a unit of ammunition underside flask and rotary evaporated to take the dissolver. The xanthous oily residue was suspended in 10 milliliter of hexane and filtrated utilizing a Pasteur pipette with a little sum of cotton on the underside. Finally the solution was rotary evaporated one time more until syrupy oil with a glue-like olfactory property remained. This would subsequently be used for brassy chromatography to farther purify and insulate the epoxide from the unreacted olefine and side merchandises. Identification| Chemical displacement ( ppm ) |
Phenolic-H| 13. 6|
N=C-H| 8. 4|
N-C-H| 3. 4|
Cyclohexane| 1. 6|
Tert-butyl| 0. 8|
After the chromatography column was made it was wet with hexane and pretreated with 20 milliliters 1 % triethylamine in hexane. The column was so rinsed with 20 milliliters of hexane and the petroleum was so added dissolved in a little sum of hexane. A 1:7 solvent mixture of ethyl ethanoate: hexane was used to elute 10 fractions with 10 milliliters each. TLC was used to place which fractions contained the epoxide. These fractions were so combined and rotary evaporated to take the dissolver. This experiment produced 0. 1052 g of epoxide or a 18. 9 % output with an enantiomeric surplus of 41. 4 % . The epoxide appeared to be a syrupy. xanthous oil. Spectra Discussion
Ligand – H-NMR
Intramolecular H bonding causes the phenolic-H to be shifted down to 13. 6 ppm from normal phenolic protein displacements of 4-8 ppm. 10 Besides because of the propinquity of the N. the imine-H is shifted down to lower field every bit good to 8. 4 ppm.
Ligand – C-NMR
Because the solution used for C-NMR is extremely diluted. noise prevents the pertinent extremums from being easy visualized. The electronegativity of the N in the imine and its hybridisation cause the C=N imine C to hold a chemical displacement of 166 ppm. Ligand – Infrared
Identification| Wavenumber ( cm-1 ) |
C=N| 1630|
O-H| 2400-3000|
sp3 C-H| 2950|
The pertinent extremums in the obtained IR are the C=N bond at 1630 cm-1. a wide O-H extremum from 2400-3000 cm-1 which is shifted to lower wavenumbers due to intramolecular H adhering between the phenolic OH H and the imine N. and a strong extremum at 2950 cm-1 for the sp3 C-H group. There appears to be two extra extremums at 1361 and 1438 cm-1 which may be due to C-H bending and puckering by the benzine pealing shifted from the normal 1600 and 1500 cm-1 due to the weakening of bonds by the negatively charged hydroxyl group. 11 There are besides two extremums at 2180 and 2017 cm-1 which may be due to presence of unreacted aldehyde. Ligand – UV-Vis
UV-Vis was done with a concentration of 10-4 M and absorbencies can be seen at wavelengths of 270 nanometers and 330 nanometer. There was a strong optical density detected at around 270 nanometers due to the ?-?*-transitions of the benzine rings while the medium optical density detected at 330 nanometers can be attributed to the ?-? and n-?*-transitions of the C=N. Catalyst – Infrared
Identification| Wavenumber ( cm-1 ) |
C=N| 1604|
sp3 C-H| 2950|
The C=N extremum in the accelerator IR is shifted down even further due to the weakening of the bond due to the coordination of the N of the imine with the manganese ion. Besides in this spectrum the wide O-H stretch is now absent which supports the reaction being complete and the ligand being depleted. The sp3 C-H stretch is still seeable since it is still present in the accelerator. Besides the extremums at 2180 and 2017 cm-1 in the ligand IR seemed to hold disappeared through the procedure demoing that farther purification was done in the procedure of synthesising the accelerator. Catalyst UV-Vis
The UV-Vis for the accelerator was done with a concentration of 2. 56 * 10-5 M. Three extremums of strong absorbencies can be seen at 200. 224. and 242 nanometer. These extremums are most likely due to ?-?* passages in the phenyl rings of the accelerator and the imine map. The deficiency of distinguishable extremums at around 496 nanometers and 436 nanometer show that the sample may hold been excessively diluted as these extremums are the 1s which give the accelerator its typical dark brown colour due to ligand field and LCMT soaking ups. Epoxide H-NMR
The H-NMR spectrum of the epoxide shows two doublets with an integrating of 4 at a chemical displacement of around 7. 2 ppm bespeaking the presence of a para-substituted arene. At a chemical displacement of 2. 5-4 ppm there are three doublets with an integrating of 1 each declarative mood of a mono-substituted epoxide. Between 0. 5 to 2 ppm at that place appears to be a batch of noise which may be due to drosss in the sample. These consequences are really similar to the literature spectra with three doublets at 2. 68. 2. 6. and 3. 07 ppm for the epoxide Hs and a multiplet at 7. 12-7. 26 ppm for the arene. 12
Epoxide C-NMR
The C-NMR spectrum shows four signals ( 2 big and 2 little ) around 130 ppm which farther supports the thought of a para-substituted arene. There are besides two signals at around 51 ppm which are due to an asymmetric epoxide. Finally there are some little extremums from 14-30 ppm which are likely once more due to drosss. Again these are really similar to the literature which has extremums at 51. 4. 51. 9 and 4 extremums around 130 ppm. 12 Epoxide GC
The GC of the epoxide gave four extremums at keeping times 21. 26. 28. and 32 severally. The extremum with the shortest keeping clip is most likely due to unreacted olefine. The extremum at 32 or the longest keeping clip is most likely due to an aldehyde or a ketone made via rearrangement of the epoxide. The extremum at 26 has a tallness of 1300000. with a breadth of 1. 3 while the extremum at 28 has a tallness of 700000. with a breadth of 1. Using these values the enantiomeric surplus was found to be 41. 4 % . Epoxide MS
The mass spectrums of the epoxide appear to hold some drosss as extremums appear above the molecular weight of 154 g/mol which appears in the literature. 13 These extremums may be due to some type of side reactions such as the formation of a dimer or may include debauched parts of the accelerator which were non separated from the epoxide wholly. From the mass spectrum it is apparent that a Cl is present as a extremum at about one-third height appears two mass per charge units higher than most of the larger extremums. The base extremum appears to be 89. 1 m/z for the epoxide with a molecular ion extremum at 154. 0 m/z. Decision
In this experiment asymmetric epoxidation of an unknown olefine was performed. After word picture of the concluding merchandise I was able to place which olefine was ab initio used. This undertaking taught me the rudimentss of epoxidation and how to read spectra to place a molecule. It besides taught me many of the techniques used in research labs and prepared me for a future calling in research. It has taught me how to research different subjects using different types of resources. This paper itself has given me experience in composing a formal study and has familiarized me with the format in which it should be written to be seen as both professional and educational.
Mentions
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10. Bacher. Alfred D. . Organic Chemistry 30CL Reader. 2011. p. 44 11. Reusch. William H. “Infrared Spectroscopy. ” Michigan State University Department of Chemistry. Web. 2011. & lt ; hypertext transfer protocol: //www2. chemical science. msu. edu/faculty/reusch/VirtTxtJml/Spectrpy/InfraRed/infrared. htm & gt ; . 12. Magerlein. Woflgang. et Al. Patent: US2006161011A1. 2006. 13. Gelalcha. Feyissa. et Al. Chemistry—A European Journal. 2008. vol. 14. 25. p. 7687-7698.
