High-Throughput Experimentation: Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling

By: Jingyuan Ma

Introduction

This lab introduced techniques used in the Penn/Merck High-Throughput Experimentation Center. The Suzuki-Miyaura reaction was implemented using 4 reagents, an assigned inorganic base, an assigned solvent, and pre-dosed phosphine ligands. TLC and HPLC were used to qualitatively analyze the reactivity trends of 24 reaction screens, which were all conducted under room temperature and controlled settings. The following overall reaction was conducted to catalyze sp2-sp2 carbon-carbon bonding through the use of a palladium catalyst:

palladium

The following is a more detailed introduction to the Suzuki-Miyaura reaction, beginning with the very initial reaction conducted by Suzuki and Miyaura:

Suzuki-Miyaura

The following is an example of a reaction that could be conducted using the Suzuki-Miyaura reaction, including a more specific mechanism:

specific mechanism

After the rate determining step of oxidative addition, where the palladium catalyst oxidizes from 0 to II and couples with the alkyl halide to produce an organopalladium complex that isomerizes from the cis to trans complex (for allylic and benzylic halides as shown previously in the two reactions), while vinyl halides retain their stereochemistry during oxidative addition. The main focus of this lab report introduction will, however, be the transmetallation step after oxidative addition.

transmetallation

In this step of the reaction mechanism, the ligands are transferred from one location to another, from the organoboron species to the PdII complex. The exact mechanism is not completely resolved, although the base is expected to activate the organoboron compound, because organoboron compounds are very covalent and unless there is a base, the transmetalation does not occur. Boronate complexes form with a negatively charged base via quaternization of the boron as shown in Fig 3.[i]

The transmetalation mechanism is still under research, as seen in the 2011 JACS publication regarding the possible pathways for the transmetalation to occur. The two ways that could be possible is that the organoboron compound is converted to a nucleophili boronate by base and attacked by a palladium halide complex or the palladium halide is converted to a nucleophilic palladium hydroxo complex that then reacts with the neutral organoboron complex.[ii] Carrow and Hartwig show that the transmetalation is between the palladium hydroxo complex and a boronic acid, not the palladium halide complex and a trihydroxyborate. This was determined by comparing stoichiometric reaction rates between isolated species. The pathway that is correct for the transmetalation within the Suzuki Miyaura cross-coupling is the one producing the largest product of the rate constant and the largest concentration of palladium complex and boron reagent.

Other recent research aims to provide the same reaction for the desired product and basis of further research of pharmaceuticals such as anticancer gossypol and antibiotic vancomycin, without the ligands. In that case, the phosphine side reactions would not exist and the reaction could be under aerobic conditions. Kumbhar, et al discovered a way for the Suzuki-Miyaura coupling reaction to occur ligand-free with the use of zeolite immobilized palladium.[iii]

 

Procedure

Day one was used to assemble 24 well blocks and lid with Teflon liner, clearly labeled with initials. Obtained five 4 mL vials with caps. The reagents provided and used were Pd(OAc)2, 4-chloroanisole, 4-bromoanisole, 4-fluorophenylboronic acid; inorganic bases: potassium phosphate and sodium carbonate, phosphine ligands in 1000uL vials. 7.2mg (ended up being 9.09mg) Pd(OAc)2, a rusty orange powder, was measured carefully into 4 mL vials, carefully labeled. 60.2mg and 60.3mg respectively of the white powder 4-fluorophenylboronic acid was weighted into each of 2 vials, carefully labeled one “4-chloroanisole” and the other “4-bromoanisole”. 2.4mmoles of the selected base was weighed into the fourth vial, however, in this case the base was pre-prepared as well as the 24 reaction vials of predosed ligands and thus the reaction setup and vials were moved to the “wet box” to prepare stock solutions. To the vial with palladium acetate, 4mL of THF was added. The vial was sealed and shaken to dissolve the palladium acetate, which dissolved completely. Using 20-100 uL pipette, 25 uL of the Pd(OAc)2 solution was dosed to each 24 predosed reaction vials. The box was then transferred back to the dry box and the blowdown tool used to remove THF solvent to leave behind palladium and ligand. While the solvent was being removed, the reaction solutions were prepared. However, in this case, the solvent and base solutions were already premade (0.890 mL of selected solvent: THF, 1.8 mL of water was added to the assigned base K2CO3 for a 1.2M base solution (premade) and for the individual step, 0.890mL of THF was added to both the 4 mL vials A and B containing the 4-fluoroboronic acid. 4.90 uL of 4-Chloroanisole was added to the 4mL vial. 50 uL of 4-bromoanisole was added to the 4mL vial B. After blowdown, transferred reaction blocks back to wet box. 50uL of the 4-chloroanisole reagent solution Vial A was dosed to each of the 12 vials A1-A6 and B1-B6. 50 uL of the 4-bromoanisole reagent solution in vial B was dosed to each of the 12 vials C1-C6 and D1D6. 50 uL of the aqueous base was dosed to each of the 24 vials A1-D6. Reaction block was caped and the lid tightened with a power screwdriver, starting from the screw in the center and working in a crisscross pattern. The box was removed from the glovebox and placed on a tumble stirrer overnight until moved into the fridge in the morning to halt the reaction.

 

Second day was used for TLC analysis. Plate 1 consisted of (in order): A1-6, product standard, 4-chloroanisole standard, B1-6. Plate 2 consisted of (in order) C1-C6, product standard, 4-bromoanisole standard, D1-6. In 95:5 hexanes:ethylacetate mobile phase, the TLC plates were ran and the solvent line was marked. The plate results were marked and compared. The HPLC calibration curve was prepared by Dr. Rarig (tared 10 mL vial, added 8-15mg of 4,4dimethylbiphenyl, added 8-15mg of product standard, 4-fluoro-4’methoxybiphenyl, added 8mL acetonitrile to vial, capped vial and shook for dissolution, transfered 1.5-2mL of this solution to HPLC vial, injected 5uL of this sample onto HPLC, recorded area under peak for the product standard (Rf=4.78 min) and the internal standard (Rf=5.64 min)).

Samples were prepared for HPLC. Using 100-1000uL multi-channel pipette, 500 uL of prepared 0.02M solution of 4,4-dimethylbiphenyl in acetonitritle was dosed into your reaction mixture. The cap was replaced on reaction block, tightened and placed on the stirplate in order to ensure all dissolved into acetonitrile. Using the 100-1000uL multichannel, 700 uL of acetonitrile was dosed into each of 24 wells on a 96 well HPLC block. The reaction block was shared between all members of the experiment, so each quadrant was well marked. After 12-13 hours, the data took about 10min per person to extract.

 

Discussion

Each solvent and base applied during the experiment is extremely important as a combination for analyzing the Suzuki coupling reactions. For this experiment, the assigned solvent was THF and the assigned base was K2CO3. It was observed in literature, Wolfe and Singer, that KF was ineffective in toluene, but most efficient promoter of coupling in THF. [iv] It was hypothesized that while biphasic solvent systems generally give poor results compared to those without water and while a combination may be a poor choice, for example, K3PO4 was less compatible with THF, reaction catalyst loads can be ran at higher (boiling point of water) temperatures in toluene for better results.

After the reaction processed, the qualitative analysis consisted of two parts: TLC and HPLC. TLC plates were visualized and produced Rf values presented in the Product Characterization section. For the quantization of which lanes consumed the aryl halide starting material and which had not. Some lanes contained multiple spots (for A6, B2, C6, D1, D5), which indicated a messy reaction. In comparison between 4-chloroanisole and 4-bromoanisole, it was concluded that reactions with 4-bromoanisole reagent (C and D vials) produced far more visible reactions via TLC as well as results within HPLC, quantized by the highest P/IS value, which correleated with the basic TLC runs (C1-5 and D1-3, 5), which did not include any of the 4-chloroanisole reagent reactions. This can be used to determine that the 4-bromoanisol reagent with THF solvent and K2CO3 base produced better results.

 

Product Characterization

Vial Ligand used: Observation: P Value P/IS Value
A1 1: Ataphos Yellow

0

0

A2 2: Butyldi-1-adamantylphosphine Milky white

0

0

A3 DPPF Yellow/orange- cloudy

0

0

A4 DTBPF Orange with percipitate

0

0

A5 P(o-toluyl)3 Peach with side precipitate

0

0

A6 P(PPh3)3 Brown-orange clear

0

0

B1 P(tBu)3 HBF4 Clear with white precipitate

3.1407E-07

0.037

B2 RuPhos Yellow with yellow precipitate

1.07619E-05

1.28

B3 S-Phos Brown

9.11845E-06

1.08

B4 Xantphos Yellow

0

0

B5 X-Phos Clear with white precipitate

1.43179E-05

1.70

B6 None Black precipitate

0

0

C1 Ataphos Orange precipitate

1.37112E-05

1.63

C2 Butyldi-1-adamantylphosphine Brown-grey precipitate

9.48693E-06

1.13

C3 DPPF Brown-red

6.34114E-05

7.52

C4 DTBPF Orange clear

5.94021E-06

0.70

C5 P(o-toluyl)3 Grey-yellow

1.40393E-05

1.67

C6 P(PPh3)3 Brown murky

1.2474E-05

1.48

D1 P(tBu)3 HBF4 Grey

1.39598E-05

1.66

D2 RuPhos Yellow-green

1.46209E-05

1.73

D3 S-Phos Yellow clear

1.06712E-05

1.27

D4 Xantphos Yellow murky

6.70446E-06

0.80

D5 X-Phos Yellow

1.03706E-05

1.23

D6 None Grey-black

5.25868E-06

0.62

Calibration - -

7.19903E-06

0.85

            0.01165 g of recrystallized product was combined with 0.01229 g of pure 4,4′-dimethylbiphenyl (internal standard) and the mixture was dissolved in 8 mL of acetonitrile.  This solution was then shot on the HPLC for analysis. These values were used for the calculation of the above P/IS values (calculation show in Question and Answer section).

Rf values from TLC- Chlorine: (solvent front: 3.15cm)

Spotting Rf Value
A1 0
A2 0
A3 0
A4 0
A5 0
A6 0.79, 0.86
Product 0.60
4-Chloroanisole reagent 0
B1 0
B2 0.57, 0.83
B3 0.57
B4 0.57
B5 0.54
B6 0

Rf values from TLC- Bromine: (solvent front: 3.10cm)

Spotting Rf Value
C1 0
C2 0.48
C3 0.45
C4 0
C5 0
C6 0.48, 0.94
Product 0.45
4-Bromoanisole reagent 0
D1 0.13, 0.29, 0.48
D2 0.58
D3 0.81
D4 0.81
D5 0.55, 0.84
D6 0.52

 

Upon comparison of the Rf values and HPLC data obtained for each reaction vial, the spotting values/characteristics did not match that of the HPLC integration values. Therefore, there must be cases of sources of error, especially in the TLC method. The TLC data most likely did not reflect the HPLC due to over-spotting, which occurred some of the trials. This resulted in blobs of spots in between lanes, which made the deciphering of the Rf values difficult. According to the HPLC, the first 6 runs of “A” or 4-chloroanisole reagent with THF solvent, K2CO3 base, and 1-6 ligand, had zero integration peaks or a no reaction, which was also reflected in the TLC in comparison to both the starting material and the product spot, except for A6. This A6 inconsistency may be due to a source of error, perhaps a poor cleaning of the thin TLC pipette, a over running of a side spot, or contamination of the plate. Visual observation of the product formation showed that although the HPLC confirmed zero integration peak, there was still visibly a precipitate, indicating that a visualization of the process is not enough for complete analysis of the 24 reactions. Ligand, solvent, and reagent combinations that produced high P/IS values were C1-5 and D1-3, 5.

 

Conclusion

According to research the use of certain types of ligands led to enhanced rate of oxidative addition while the catalytic cycle was also sped up unlike the common result of one step speeding and another slowing down. The ligands are therefore successful in their purpose of applying their electron-richness to the palladium and their bulkiness to increase the rate of reductive elimination and increase the amount of L1Pd complexes to increase the rate of transmetalation. The following experiment using the High-Throughput Experimentation Center allowed for the further understanding of screening multiple reactions within a limited amount of time, analyzing the results, and comparing the effectiveness of different solvents, ligands, and bases. Understanding each factor that contributes to the reaction process helps develop future experiment protocols and develop ideal conditions for desired reactions.

Assigned Questions

  1. See introduction
  2. Values from your calibration solution (reaction product and internal standard), calculate P/IS value that corresponds to complete conversion. Molar ratio of product to internal standard in your calibration solution? What was the relative area ratio for that sample? What is the molar ratio of theoretical product formation to our internal standard that we dosed into each reaction vial?

Molar ratio: theoretical product formation: 0.01165g/[202.228 g/mol]= molar quantity of product theoretical=5.8e-5mol. Internal standard (pure 4,4′-dimethylbiphenyl) of 0.01229g/[182.26g/mol]=6.74e-5mol internal standard.

Relative area ratio: product peak integration: internal standard peak integration approximate to product: internal standard molar ratio.

 internal standard molar ratio.

areaAny observed reactivity trends. Compare qualitative TLC assessment with quantitative HPLC data. What are the shortcomings of the TLC? Benefits? Short comings and benefits of HPLC?

TLC assessments are a way to observe reactivity trends. They were used to quickly assess each of the 24 reactions, which allowed the assessment to be a fast and easy way to visually compare the reactivities. However, TLC plates are also not completely reliable because the plates don’t have long stationary phases and the detection limit is high. The data obtained would just be a rough estimate and other chromatographic techniques may be used. Also, the plates were crudely placed in a beaker with solvent and the system was somewhat open, only slightly covered by aluminum foil. The many environmental factors and high likelihood of dots being overspotted, running into each other, streaking, and uneven solvent front all contribute to the shortcomings of the TLC technique.

HPLC can be run for many reactions at a fast rate and with far more accuracy. The results are easily reproducible and easy to operate. It can also be used for more complex molecules and However, these are very expensive to obtain, use, and maintain in a laboratory.

Any problems? What would you change to improve the experience?

The experience was great in the laboratory. The groups were split up well so that everyone got a section of the glovebox and took turns in a timely fashion. The calendar was poorly organized in that there were due dates that were different between the groups and I felt that I had to turn in 3 labs without getting feedback on them, which lost me a few points on technical issues.

[1] N. Miyaura and A. Suzuki, “Palladium-Catalyzed Cross- Coupling Reactions of Organoboron Compounds,” Che- mical Reviews, 1995, 95, 7, 2457-2483.

[1] Coletta, Chris, and Andrew Haidle. “The Suzuki Reaction.” Havard Chemistry 215. N.p., n.d. Web. 22 Nov. 2013. <http://www.chem.harvard.edu/groups/myers/handouts/12_Suzuki.pdf>.

[1] Carrow, Brad P., and John F. Hartwig. “Distinguishing Between Pathways for Transmetalation in Suzuki-Miyaura Reactions.” Journal of the American Chemical Society 2011, 133, 2116-119.

[1] Kumbhar, Arjun, Santosh Kamble, Anand Mane, Ratnesh Jha, and Rajashri Salunkhe. “Modified Zeolite Immobilized Palladium for Ligand-free Suzuki–Miyaura Cross-coupling Reaction.” Journal of Organometallic Chemistry 2013, 738, 29-34.Science Direct. Web. 20 Nov. 2013. <http://www.sciencedirect.com/science/article/pii/S0022328X13002325>.

[1] Wolfe, J.P.; Singer, R.A.; Yang, B.H.; Buchwald, S.L. Journal of American Chemistry Society 1999, 121, 9550-9561.

 

The Diels-Alder Reaction

By: Kayla Powers and Jakkrit Suriboot

cyclopentadiene

Introduction Diels-Alder reactions are used for synthesizing new carbon-carbon bonds and more specifically, six-membered cyclic compounds. In addition, this reaction synthesizes compounds that are otherwise difficult to obtain, such as bridged bicyclic compounds.  A key characteristic of these reactions is their stereospecificity.  Based on the interaction between a conjugated diene and a dienophile, different stereoisomeric compounds are formed.   The Diels-Alder reaction is categorized as a pericyclic reaction, which involves the overlap of spatial orbitals as well as the hybridization and delocalization of the molecules.1  As a unique characteristic, this reaction is characterized as a concerted cycloaddition reaction indicating a lack of intermediate in the mechanism.

Stereochemistry represents a major component of the Diels-Alder reaction.  Due to the interaction and arrangement of a cyclic diene and a dienophile, an endo and exo product can be formed characterizing the reaction as stereo- and regioselective. By analysis of NMR spectroscopy and physical properties of the specific isomers, the difference between the possible products can be identified.

Interesting products of the Diels-Alder reaction are cyclic compounds with chlorine-containing substituents that act as powerful insecticides.  Insecticides have been commonly used to treat pests in various types of fruits, vegetables, and crops.  Because of the negative affect on the environment, certain pesticides have remained unused and alternative methods involving the elimination of pests have been investigated.  Strategies, such as using hormones have been explored with haste because of the potential damage many pests have on agricultural produce.2  These compounds have been researched and related back to their concerted cycloaddition mechanism.

Reaction Mechanism The scheme below depicts the concerted mechanism of the Diels-Alder reaction of cyclopentadiene and maleic anhydride to form cis-Norbornene-5,6-endo-dicarboxylic anhydride.

diels-alder reaction

Results and Discussion When combining the reagents, a cloudy mixture was produced and problems arose in the attempt to completely dissolve the mixture.  After heating for about 10 minutes and magnetically stirring, tiny solids still remained. The undissolved solids were removed form the hot solution by filtration and once they cooled, white crystals began to form. Regarding the specific reaction between cyclopentadiene and maleic anhydride, the endo isomer, the kinetic product, was formed because the experiment was directed under mild conditions.   The exo isomer is the thermodynamic product because it is more stable.3

A total of 0.47 g of the product was collected; a yield of 27.6%. The melting point was in the range of 163-164 °C which indicates the absence of impurities because the known melting point of the product is 164 °C.

Cis-Norbornene-5-6-endo-dicarboxylic anhydride

The 1H NMR spectrum of the product revealed a peak in the alkene range at 6.30 ppm, H-2 and H-3 (Figure 1).  In addition, it exhibited two peaks at 3.57 and 3.45 ppm because of the proximity of H-1, H-4, H-5, and H-6 to an electronegative atom, oxygen.  Finally, two peaks at 1.78 and 1.59 ppm corresponded to the sp3 hydrogens, Hb and Ha, respectively.  Impurities that appeared included ethyl acetate at 4.03, 2.03, and 1.31 ppm as well as acetone at 2.16 ppm.

Regarding the 13C NMR, a peak appeared at 171.3 ppm, accounting for the presence of two carbonyl functional groups, represented by C-7 and C-8 in Figure 1.  The alkene carbons, C-2 and C-3, exhibited a peak at 135.5 ppm, while the sp3 carbons close to oxygen, C-5 and C-6, displayed a peak at 52.7 ppm.  Finally, peaks at 46.1 and 47.1 ppm accounted for the sp3 carbons, C-1 and C-4, and C-9.  Impurities of ethyl acetate appeared at 46.6, 25.8, and 21.0 ppm accompanied with acetone at 30.9 ppm.

The IR spectrum revealed a peak at 2982 cm-1 representing the C-H stretches.  A peak at 1840 cm-1 accounted for the carbonyl functional group, while a peak at 1767 cm-1 accounted for the alkene bond.  A peak at 1089 cm-1 represented the carbon-oxygen functional group.

In order to distinguish between the two possible isomers, properties such as melting point and spectroscopy data were analyzed.  The exo product possessed a melting point in the range of 140-145 °C which is significantly lower than the endo product.  The observed melting point in this experiment supported the production of the endo isomer. The 1H NMR spectum exhibited a doublet of doublets at 3.57 ppm for the endo isomer.  The exo isomer would possess a triplet around 3.50 ppm due to the difference in dihedral angle between the hydrogen molecules of H-1 and H-4, and H-5 and H-6 (Figure 1).  A peak at 3.00 ppm would appear in the exo isomer spectra as opposed to a peak at 3.60 ppm as shown in the observed endo product.3 This is because of the interaction and coupling with the H-5 and H-6, as displayed in Figure 1.

 

Conclusion Through the Diels-Alder reaction, 27.6% yield of cis-Norbornene-5,6-endo-dicarboxylic anhydride was produced. The distinction of the presence of the endo isomer was proven by analyzing physical properties of both possible isomers.

 

Experimental

General: All reagents were provided by Sigma-Aldrich from Texas A&M University Chemistry Department. 1H and 13C spectra were taken on a Mercury 300 MHz NMR spectrometer.  An IR spectrum was recorded on PerkinElmer UATR Two Spectrophotometer.

 

Cis-Norbornene-5,6-endo-dicarboxylic anhydride Cyclopentadiene was previously prepared through the cracking of dicyclopentadiene and kept under cold conditions.  In a 25 mL Erlenmeyer flask, maleic anhydride (1.02 g, 10.4 mmol) and ethyl acetate (4.0 mL) were combined, swirled, and slightly heated until completely dissolved.  To the mixture, ligroin (4 mL) was added and mixed thoroughly until dissolved.  Finally, cyclopentadiene (1 mL, 11.9 mmol) was added to the mixture and mixed extensively.  The reaction was cooled to room temperature and placed into an ice bath until crystallized.  The crystals were isolated through filtration in a Hirsch funnel.  The product had the following properties: 0.47 g (27.6% yield) mp: 163-164 °C (lit: 164 °C).  1H NMR (CDCl3, 300 MHz) δ: 6.30 (dd, J=1.8 Hz, 2H), 3.57 (dd, J=7.0 Hz, 2H), 3.45 (m, 2H), 1.78 (dt, J=9.0,1.8 Hz, 1H), 1.59 (m, 1H) ppm.  13C NMR (CDCl3, 75Hz) δ: 171.3, 135.5, 52.7, 47.1, 46.1 ppm.  IR 2982 (m), 1840 (s), 1767 (s), 1089 (m) cm-1.

Supporting information IR, 1H NMR and 13C NMR spectra of cis-norborene-5,6-endo-dicarboxylic anhydride are attached.

1 Martin, J.; Hill, R.; Chem Rev, 1961, 61, 537-562.

2 Pavia, L; Lampman, G; Kriz, G; Engel, R. A Small Scale Approach to Organic Laboratory   Techniques, 2011, 400-409.

3 Myers, K.; Rosark, J. Diels-Alder Synthesis, 2004, 259-265.

 

Determination of Mn in Steel

By: Juno Kim and Nicole

Introduction

            The goal of this experiment was to determine the mass percent of manganese in an unknown steel sample using methods of visible spectroscopy and volumetric analysis. The two methods were then analyzed and compared to decide the better method for determining the composition of Mn in the unknown steel. In both methods, the unknown steel was digested in hot concentrated Nitric acid, HNO3, and analyzed for transition metals. An accurate analysis of steel composition is important because the mass percent of carbon and transition metals in the steel determine its properties such as strength, conductivity, ability to be altered by heat, and corrosiveness that ultimately decide the steel’s usage. An alloy is a mixture of two or more elements, one of them being a metal, and steel is an alloy of iron containing small amounts of transition metals. Adding carbon to iron creates steel which has versatile uses for its general properties.

Pertaining to this lab, knowing the composition of steel reveals the best form of usage. For example structural steels contain alloying elements like Mn that can be used to produce complex structures and machine parts while tool steels have higher carbon mass percentage and contain alloying elements such as chromium. Compared to iron, steel is tougher with high strength and has the ability to greatly alter form through heat treatment. Adding Chromium to steel produces stainless steel that resists corrosion and adding silicon to steel creates silicon steel used for electronic purposes. The composition of steel must be determined and double checked prior to its intended use to avoid consequences as large as a bridge collapsing due to the use of inadequate steel. The methods of determining the composition of steel can also be used to analyze the strength and durability of already standing structures that have been subject to corrosion and weathering as well. The main objective of the experiment was to determine the manganese composition of the steel unknown by the methods of standard additions, involving visible spectroscopy, and volumetric analysis, involving back titration.

Experimental Methods

I. Standard Addition

The standard addition method used visible spectroscopy to determine the concentration of

manganese in the unknown steel sample. Standard addition is used to account for the potentially interfering ions from other transition metals.2 To start with, the sample of unknown steel was digested in hot nitric acid. Precisely 1.0437g of steel unknown and 50 mL of 4M nitric acid, HNO3, were added to a 250mL beaker and brought to a gentle boil. The beaker was covered with the watch glass to avoid losing its contents through splattering. It took close to an hour for all of the unknown steel to dissolve so excess 4M HNO­3 was added during the digestion to displace the evaporated liquid and keep the volume close to 50 mL. After digestion, 1.0 g of ammonium peroxydisulfate, [(NH4)2S2O­8], was slowly added to the beaker and put to boil for 15 minutes. During the boil, peroxydisulfate oxidizes any carbon in the sample in the reaction shown below:

2S2O82- + C + 2H2O -> CO2 + 4SO42- + 4H+

Following the procedure, 0.1 g of sodium bisulfate (NaHSO3) was added while heating and the resulting solution was left to cool to room temperature and transferred to a 250 mL volumetric flask where it was diluted with distilled water to the mark. Note that NaHSO3 solution was added to reduce any permanganate that may have formed through this reaction:

5HSO3- + 2MnO4- + H+ -> 2Mn2+ + 5SO42- + 3H2O

            Following the steel digestion, the standard Mn solution was prepared. For that 100 mg of Mn was dissolved in 10 mL of 4M HNO3 and put to boil to remove nitrogen oxides. The resulting solution was diluted to the mark with DI water in a 1 L volumetric flask.

After the necessary solutions were prepared, standard additions took place. Total of seven samples were prepared for the spectroscopy and in each sample 20 mL aliquot of the digested steel was put into a 250 mL beaker. Then 5 mL of 85% phosphoric acid was added to eliminate iron(III) as a source of interference when taking the spectroscopy. Samples of standard Mn2+ and solid potassium periodate were added to the beaker according the table I provided below:

Table I: Calibration Standard Sample Volumes

Sample

Steel

H3PO4

Standard Mn

KIO4

1-blank

20 mL

5 mL

0 mL

0g

2

20 mL

5 mL

0 mL

0.4g

3

20 mL

5 mL

1 mL

0.4g

4

20 mL

5 mL

2 mL

0.4g

5

20 mL

5 mL

3 mL

0.4g

6

20 mL

5 mL

4 mL

0.4g

7

20 mL

5 mL

5 mL

0.4g

Upon heating, KIO4 oxidizes Mn2+ to a permanganate ion in the reaction given below:

2Mn2+ + 5IO4- + 3H2O -> 2MnO4- + 5IO3- + 6H+

Each of the samples were boiled for 5 minutes and cooled before being diluted in a 50 mL volumetric flask. Then, using the UV-Visible spectrometer, absorbance at the max wavelength for permanganate ion was measured. The max wavelength for the permanganate ion is 525 nm and the analyzers are designed to measure the absorbance in a particular wavelength band1. Small aliquots of each sample were added to a cuvette to measure the absorbance and a linear graph was expected with no absorbance value greater than 1.0 for any of the samples. At the end, the absorbance of the blank solution, containing no Mn or KIO4, was deducted from the other samples’ absorbance values. The line of best fit for the plot of concentration of added Mn2+ vs. the absorbance was drawn to find the x-intercept which represented the concentration of Mn in the unknown steel sample. The concentration of added Mn2+ was calculated by using the concentration of the standard Mn solution as shown below:

100.0 ppm * (mL of Mn added/50 mL) = concentration of Mn in ppm

II. Volumetric Analysis

            Determination of Mn in the unknown steel through volumetric analysis involved titrations. A standard potassium permanganate (KMnO4), standard Ferrous Ammonium Sulfate (Fe(NH4)2(SO4)2), and an unknown steel sample were prepared in lab for the titration of the unknown steel sample.

The KMnO4 solution was prepared by glass filtering 100 mL of 0.1 M KMnO4 solution through a sintered glass filter. The resulting solution was then transferred to a 1 L volumetric flask and diluted to the mark with DI water. To standardize this solution, solid sodium oxalate was put to dry in an oven for an hour. Then three 100 mg samples of dried sodium oxalate were transferred to 250 mL beakers along with 100 mL of 0.9 M sulfuric acid (H2SO4) and heated. While heating, a burette was filled with the permanganate solution and its initial volume was recorded. A single drop of the permanganate solution was added to each of the beakers while heating and the titrations commenced once the pink color from the permanganate disappeared. The reappearance of the pink color marked the end of titrations. The reaction of permanganate with oxalate is as follows:

2MnO4- + 5C2O42- + 16H+ -> 2Mn2+ + 10CO2 + 8H2O

Using stoichiometry, the concentration of MnO4- in the solution was calculated using the formula:

0.100g C2O4- * (1 mol/88.01928g C2O4-) * (2mol MnO4-/5 mol C2O4-) *(1/L of MnO4- used)

Taking the average of the three trials yielded a MnO4- concentration of 0.0148 M in the standard solution.

For the preparation of standard Fe(NH4)2(SO4)2 solution, about 12 grams of ferrous ammonium sulfate hexahydrate were added to a 1L volumetric flask and dissolved in 1:20 sulfuric acid (H2SO4). The solution was diluted to the mark with 1:20 H2SO4. For the standardization process, 25 mL of 1:30 nitric acid (HNO3) was added to a 250 mL Erlenmeyer flask using a volumetric pipette. Then 25 mL of Fe(NH4)2(SO4)2 was added and the resulting solution was titrated with KMnO4 until the pale pink endpoint. The ferrous ions react with MnO4- in the redox reaction given below:

MnO4- + 5Fe2+ + 8H+ -> Mn2+ + 5Fe3+ + 4H2O

Using stoichiometry, the concentration of the ferrous ion, Fe2+, was calculated using the formula:

(Volume of KMnO4 used) * 0.0148M KMnO4 * (5 M Fe2+/1 M MnO4) * (1/volume of sample)

Taking the average concentrations of four trials yielded a Fe2+ concentration of 0.0466 M in the standard solution.

For the preparation of steel unknown sample, 0.2351 g of the unknown steel sample was added to a 250 mL beaker. The manual states a whole gram of the unknown steel should be used, but after a few failed trials with the first method, only 0.2351 g of the unknown steel was left for analysis. Then 50 mL of nitrous acid free 1:3 HNO3 was added to the beaker and the contents were put to a gentle boil under a watch glass cover. Once all the steel dissolved, the beaker was removed from heat and 0.5 g of sodium bismuthate (NaBiO3) was added. After the addition of NaBiO3, the contents were boiled for another five minutes which after, the solution turned purple so there was no need to add additional grams of NaBiO3. The resulting purple solution was removed from heat and drops of sodium sulfite (NaSO3) were added until the purple color disappeared (3 drops used). Then the solution was put to boil and became rust orange in color after 5 minutes. The beaker was cooled in an ice bath and allowed to chill and after, 0.7 g of NaBiO3 was added to form a solid NaBiO3 inside a purple solution. The reaction of bismuthate with manganese ion is shown below:

2Mn2+ + 5BiO3- + 14H+ -> 2MnO4- + 5Bi3+ + 7H2O

To transfer the solution, a sintered glass filter was used instead of filter paper which the Mn could react with. The filter was washed with 1:30 HNO3 and the solution inside the beaker was filtered into a flask. After filtration 4 mL of 85% phosphoric acid (H­3PO4) was added to the filtrate and mixed. The resulting solution was then transferred to a 100 mL volumetric flask and diluted to the mark with 1:30 HNO3.

After the necessary solutions were prepared, the titration of the unknown steel 64 commenced. 25 mL of the (Fe(NH4)2(SO4)2) solution as well as 25 mL of the steel unknown solution were added to an Erlenmeyer flask using a volumetric pipette. The purple color disappeared as the steel unknown reacted with the ferrous ions. Then the solution was back titrated to the pink endpoint with the standard KMnO4 solution. In this back titration, an excess of standard (Fe(NH4)2(SO4)2) was added to the steel unknown, turning the color clear as the ferrous ions reacted. Then the excess (Fe(NH4)2(SO4)2) was titrated with the standard KMnO4 until the endpoint which was signaled by the reemergence of the pale pink color. Once all the Fe2+ ions have reacted, MnO4- remained in the solution to signal the end of the back titration with the pale pink endpoint. The net ionic equation is:

MnO4- + 5Fe2+ + 8H+ -> Mn2+ + 5Fe3+ + 4H2O

The percentage Mnin the steel unknown was calculated by the formula below:

the formula

Results

The results from the two different methods were synchronized. The Mn contents of all the unknowns vary from 0.10% to 1.00% so both methods gave an acceptable result.

The Beer’s law states that absorbance is proportional to concentration. The calibration plot of UV-Vis supports the law. Beer’s law:

A = εlc

‘A’ represents absorbance with no units. ε is the molar absorption coefficient with units Lmol-1cm-1. ‘l’ represents the path length of the cuvette and ‘c’ is the concentration of the compound in solution expressed in molL-1. Another form of Beer-Lambert’s law is:

I = I010^-εcL 3

‘I’ is the transmitted intensity, varying with the length L and I0the incident intensity.2 UV and visible spectra are plots of absorbance against the wavelength in nanometers. Its absorbance is related to concentration by the Beer-Lambert’s law.4

A = log(I0/I) = εlc 4

Discussion

            The weight percentage of Mn in the unknown steel sample was calculated as .51% with 95% confidence interval of 0.71 from the visual spectroscopy method. The absorption of the blank sample containing no standard Mn or KIO4 was measured to be 0.0395. The measurement of the second sample yielded absorption value of 0.4020. After subtracting the blank absorption value the first sample’s absorption was 0.3625. This was a lot higher than 0.1 absorption value the second sample should be at so the absorption values along with the steel sample volume were adjusted through division by 4. The 95% confidence interval value of 0.71 is very high. The cause of error in this method most likely resulted from the fact that the steel unknown solution had small precipitates that would not dissolve. Such error may be alleviated by letting the solution sit for a period of time until the precipitates fall to the bottom of the flask. Then samples could be taken from the top of the solution without any precipitate using a pipette. The steel unknown sample took 45 minutes longer than anticipated to digest during the lab and even after the digestion there were some particles left in the solution. This could be from impurities of the unknown steel sample. The digestion process could be sped up next time by preparing a hot HNO3 to digest the steel unknown.

The volumetric analysis also gave a Mn concentration of 0.51% in the unknown steel with the 95% confidence interval of 0.16. For this experiment, judging from the lower value for the confidence interval, this method of back titration gave more reliable concentration of Mn in the steel #64. Note that instead of using 1 g of the unknown steel sample, only 0.2351 g was used because that is what was left available. The volumes of KMnO4 used to back titrate the mixture of 25 mL unknown steel solution and 25 mL (Fe(NH4)2(SO4)2) were very consistent and consequently, they yielded consistent Mn weight percentage values in the three trials. The weight percentages of Mn for the three trials were found to be 0.52%, 0.51%, and 0.50% with the low variance of 0.02. The standard deviation, 0.1414, was calculated by square rooting the variance. The standard error, which was multiplied by 1.96 to give 95% confidence margin of error, was calculated by dividing the standard deviation by the square root of the number of trials. The confidence interval, calculated as 0.16, is still high considering the precise Mn percentage values. This could be amended by increasing the number of trials which would bring down the values (assuming the same, precise Mn percentages are calculated).

Comparing the two, both methods gave a very precise concentration of Mn in the unknown steel. The volumetric analysis had a much lower value for its confidence interval so for this experiment the back titration proved to be the better method. The visual spectroscopy method was easier in a sense that the UV-Visible spectrometer measured the absorbance for each of the prepared cuvette samples left to be graphed and analyzed. However the slight problem with this method is the fact that it relies on the line of best fit to find the concentration of Mn in the sample, making it more prone to errors by inaccurate measurements.

The volumetric analysis involved preparing two standard solutions and an unknown steel solution before the titration of the steel unknown. This method gave the experiment more control because the standard solutions were made in lab and their concentrations were calculated using stoichiometry from the redox equations. It was also easy to tell if a certain titration has gone wrong by looking at the volumetric data and noticing an outlier among the volumes used for the same titration. In this method it was critical to keep the prepared solutions from being affected by impurities. That was achieved by transferring small amounts of the standard solutions into beakers and drawing samples from the beakers. That prevented the standard solutions from being contaminated through multiple aliquots drawn by a pipette.

Conclusion:

The purpose of the experiment was to find the concentration of Mn in an unknown steel sample through the method of standard additions, involving visible spectroscopy, and volumetric analysis, where the concentration was calculated through back titration. The volumetric analysis proved to be a better method since the standard addition method’s calibration plot of the UV-Visible spectrometer yielded a faulty 0.71 margin of error under a 95% confidence level. Such margin of error is unacceptable considering the Mn concentration falls outside probable range between 0.1% and 1% after just one standard deviation away from the mean. After back titrations, the Mn concentration in the unknown steel was found to be 0.51% with 0.16 margin of error under a 95% confidence. Adding Mn to steel increases the steel’s toughness and strength and analysis of the concentration of Mn or other transition metals in steel as well as carbon can reveal the properties of the steel and its practical usage.

 

References

1 Laverman, L.E. Experiments in Analytical, Physical and Inorganic Chemistry, 3rd Edition; p.

14.

2 Green, Don W., Perry, Robert H. Perry’s Chemical Engineer’s Handbook, 8th Edition;

McGraw-Hill: New York, 2008, p. 8-62.

3 Atkins, Peter., Paula, Julio de. Physical Chemistry, 9th Edition; W.H. Freeman and Company:

New York, 2010, p. 490.

4 Mohrig, J.M., Hammond, C.N., Schatz, P.F. Techniques in Organic Chemistry, 3rd Edition; W.

H. Freeman and Company: New York, 2010, p. 429.

Multi-step Synthesis of Fragrances

Written by Conner Dart

Introduction:

The purpose of this experiment was to create and purify a product from 2 different reactions. The first reaction was a reduction of an aldehyde and the second was an acid-catalyzed etherification. This type of reaction is important because from it many derivatives (fragrances) are created. This is called organoleptic chemistry. In order to achieve this derivative, separatory funnels were used, reflux was utilized in coordination with TLC analysis in some cases, rotary evaporation was used and finally column chromatography to purify the product. To analyze said product and its intermediate, TL and NMR techniques were utilized.

Reactions:

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Mechanism:

Reduction-

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Etherification-

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Procedure:

To begin the experiment, 1.49 g of Aldehyde B (Piperonal) were dissolved in 10 mL of MeOH in a

125 mL Erlenmeyer flask. The flask was then placed in an ice water bath and 0.4 g of sodium borohydride were added in small portions and the flask was removed for 25 minutes until the bubbling ceased. The flask was then placed back into the bath and 10 mL of 3 M HCl were added. This was swirled until the bubbling subsided. 20 mL of ethyl acetate were added to the flask and transferred to a separatory funnel. The organic layer was extracted by adding 10 mL of water twice and 10 mL of saturated NaCl once. The organic layer was then transferred to a clean flask. Magnesium sulfate was added to absorb the extra water and this was gravity filtered into a round bottom flask to be rotary evaporated. 1.029 g of the intermediate (Piperonyl alcohol) were created. The IR and NMR were obtained for characterization and purity analyses.

0.5 g of Amberlyst 15 beads were placed into a 100 mL round bottom flask and washed with 5 mL ethanol. 5 mL of ethanol were added to the beads and 0.743 g of Piperonyl alcohol was dissolved in another 5 mL of ethanol. A drop of the mixture was added to a TLC plate to determine when the starting material was no longer in the flask. The solution was refluxed for 45 minutes until the TLC plate showed no sign of starting material. Then the solution was gravity filtered into a small beaker and the flask was washed with methylene chloride. This solution was transferred to a separatory funnel and 20 mL of methylene chloride were added and the organic layer was drained into another flask since it was on the bottom. The drained layer was then washed thrice with 10 mL of water. Magnesium sulfate was added and the solution was gravity filtered and rotary evaporated. The mass of the crude product was .385 g.

The third part of the experiment was the purification of the ether by column chromatography. A column was set up and the hexane to ethyl acetate solvent ratio was determined to be 6:1 by TLC analysis. Fractions were run off the column until the there was a pure product determined by TLC with a Rf around .3. Those fractions were then rotary evaporated and the mass of the pure product was 0.243 g.

Results:

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Intermediate Yield-

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Product Yield-

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TLC Analysis-

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IR Spectroscopic Data-

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NMR Spectroscopic Data-

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Discussion:

The goal of this experiment was to carry out a multiple-step synthesis reaction in order to develop a benzyl ether derivative. This was done by reduction the aldehyde to create an alcohol and then performing an etherification reaction by adding another alcohol. These reactions have major importance because of the variety of the derivatives that can be created from a single aldehyde, a science called organoleptic chemistry. Major procedural techniques were reflux, funnel separation, and rotary evaporation. Reflux is a technique that accelerates and maximizes the efficiency of a chemical reaction by stirring and heating a solution. Funnel separation is a purification technique that allows for the organic layer of a solution to be removed from the aqueous layer after a reaction, this will remove some of the solvents or reagents and what doesn’t get removed will be in rotary evaporation. Rotary evaporation removes the solvent from the solution which then solidifies the desired product. Major analysis techniques were IR, NMR, and TLC in this lab. IR spectroscopy exposes the organic molecules to infrared radiation and based on the energy given off by the vibrations of the bonds in the molecule, absorption occurs and an IR spectrum can be given. NMR calculates the energy of protons based off aligning and opposing spins caused by a magnetic field. TLC uses a solvent that carries the pieces of a spot up a plate based on the polarities of its components. The major purification technique utilized in this lab was column chromatography. It is similar to TLC in that an eluent carries components of a solution through a stationary phase, but in column chromatography the components are able to be separated and therefore isolated into pure products.

To start the multi-step synthesis, the aldehyde was reduced to an alcohol. This was done by utilizing the reducing agent, NaBH4, to decrease the number of oxygen bonds from 4 to 3 and then the addition of acid allowed for the increase of hydrogen bonds to form the alcohol. This process was then purified by using separatory techniques. Ethyl acetate was used to dissolve the solids, so the organic

layer was on top when the separatory funnel was settled. Once the organic layer had been washed a rotary evaporator was used in order to evaporate impurities and change the liquid intermediate into solid intermediate. Here, 1.029 g of the intermediate (piperonyl alcohol) was created. A possible error in the yield could have been from not allowing the reaction to go to completion after the addition of NaBH4. IR and NMR spectroscopy was used in order to determine the purity of the intermediate. IR spectroscopy showed a peak at 2986.82 cm-1 which correlated to a C-H bond which should be expected in any organic molecule, but the peaks that were specifically consistent with its structure were at 1490.07 cm-1, 1275.61 cm-1, and 810.03 cm-1. These peaks correlated to a C=C aromatic bond, C-O alcohol bond, and C-H aromatic bond. Even though most of these peaks were weak in strength, they were necessary in determining the structure. There were some peaks missing in accordance to the structure, so the intermediate wasn’t all that pure. This could be a possible error in yield and purity going on with Parts 2 and 3 in the experiment. The NMR was a little cluttered, but a ratio on the integration was found in order to get better results. There were 6 main peaks, 3 of which that fell in the aromatic region (6.5 – 8 ppm) and 1, at 2.03 ppm, corresponded to the hydrogen on the alcohol group. The assignments, therefore, were easily justified and although the NMR seemed to have extraneous peaks, the data reported was fairly accurate.

In Part 2, 0.743 g of piperonyl alcohol was used in the acid-catalyzed etherification reaction. The reaction was refluxed until all of the starting material had been converted into product. This was monitored by TLC analysis; 3 spots were made for these analyses, the first was of the starting material, second was a combination of the starting material and the refluxed solution, and the third was solely the refluxed solution. The reaction was deemed complete when the analysis showed that the product was isolated without starting material and this was confirmed when TLC had one mark on the third spot that was higher up the plate than the starting material. More separation techniques were utilized to further purify the product and a rotary evaporator removed the solvent from the product.

The next step was to purify the product and this was done by column chromatography and TLC analysis. The eluent wasn’t given in this step; so in order to find a sufficient eluent, TLCs were run until the product had an Rf value of 0.3. This Rf value was found having a solvent in a 6:1 hexane to ethyl acetate ratio. This solvent was used as the mobile phase in the column chromatography and only pure fractions with an Rf value around 0.3 were transferred to a flask for rotary evaporation. Fractions 7-9 were found to be the purest and after rotary evaporation, 0.243 g of product was made. This amount is barely a quarter of the theoretical yield (27.61%), which suggested that errors were made during column chromatography. One such error could have been having too large of fractions; this would cause some of the either starting material or other reagents to run-off into the pure compound fractions. On the TLC analysis it would show up as impure even though there is some compound in it which would create less yield. Once the solid was collect IR and NMR samples were prepared and analyzed. The IR was accurate and had all significant bond types including both aromatic and aliphatic C-O ether bonds. This was a crucial difference in the product compared to the intermediate’s IR. They both had aromatic peaks, but the ether in the product was a major difference in determining the purity of the product. The IR again was a little cluttered, but during the analysis, 7 different protons were able to be found. The extra proton came from the ethanol reacting with piperonyl alcohol to get an ethyl chain as a part of the ether. These protons on the chain were easily spotted because of the multiplicity. All the aromatic protons a part of the piperonyl chain were either singlets or doublets, and the ethyl chain had a quartet and triplet. The integration again had to be reduced by a factor in order to get the correct numbers. Although the yield was relatively low, the NMR was fairly accurate. The product and intermediate also had the 3 different protons in the aromatic region (6.5-8 ppm) in both NMR which is accurate with the structure and then another proton at around 5.9 ppm for both which correlated to the set in the ring at the very bottom of the molecule.

POST LAB QUESTIONS:

1. The advantage of Amberlyst 15 beads being used is that they do not dissolve, so when added to the system they are easily separated by gravity filtration once the reaction is complete. This also makes the neutralization of the solution simple, because simply removing them from the solution causes neutralization.

2.

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NaBH4 is a reducing agent, and the aldehyde group can be reduced to an alcohol because it is on a primary carbon.

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NaBH4 is a reducing agent, and the ketone group can be reduced to an alcohol because it is on a secondary carbon.

The last reagent won’t react because the alcohol on the primary carbon won’t be reduced further and the bottom half of the molecule is unreactive due to stability

3. a. If the HCl were not added to the first part, then the reduction of the aldehyde would not have been complete, the oxygen would have remained with a negative charge and therefore would have been washed away during the separatory funnel technique. Therefore no product would have been made because no intermediate would have formed.

b. If NaOH were added instead of HCl, then essentially the same thing would happen. Since the oxygen has a negative charge from the reduction, it wouldn’t have been neutralized and no intermediate or product would be formed.
c. If the Amberlyst beads were not removed, then the solution would have not been neutralized and after evaporation, there would be an artificially high mass.

d. If the organic layer wasn’t washed with water, then the charged species that didn’t fully react would still be in the solution and wouldn’t be separated to the aqueous layer. This would cause an artificially high mass again and would affect the purity of the product.

 

Multistep Reaction Sequence: Benzaldehyde to Benzilic Acid

Seth Dingas* and Jakkrit Suriboot

ABSTRACT

Benzilic acid

Benzilic acid was synthesized through a multistep reaction from the starting material of benzaldehyde and through the formations of benzoin and benzil.  The first reaction produced benzoin by using the thiamine hydrochloride catalyst, followed by an oxidation reaction to produce benzil, and a rearrangement to synthesize benzilic acid.  By utilizing crystallization, pure solid products of each step were collected and analyzed through IR, NMR spectroscopy, and other physical properties.

Introduction
Multistep synthesis reactions involve many advantages and disadvantages.  Disadvantages include time-consuming experiments, error within intermediate steps, or the presence of side reactions.  Advantages imply the production of ideal, marketable end products, and the synthesis of compounds that otherwise could not be produced through a simple reaction.  Research has enhanced the sustainability, time efficiency, and design of multistep synthesis reactions to be utilized in many industrial situations.1

Different organic processes and characteristics were utilized in the multistep synthesis involved in this reaction.  Green chemistry was involved in the preparation of benzoin by the choice of catalysis, thiamine hydrochloride.  In a biochemical environment, thiamine acts as a coenzyme that proceeds as the chemical reagent.2  Regarding the second step, an oxidation reaction was involved utilizing a mild oxidizing reagent, nitric acid, in pyridine.  Finally, the third step of this reaction involved the compound benzil that has attracted many speculations throughout the century.  Through the interaction with other molecules, the rearrangement characteristics of benzil have been proven based on the intramolecular oxidation and reduction forces of gaining and losing electrons.3 Overall, the combination of the various organic characteristics and experiments allow for the success of a multistep synthesis reaction.

Reaction Mechanisms
Scheme 1 depicts the reaction between the catalyst thiamine hydrochloride and two equivalents of benzaldehyde.  Once a proton was removed from thiamine hydrochloride, forming ylide, it acted as a nucleophile that allowed for the addition of the carbonyl group of benzaldehyde. A proton is removed from the intermediate and the new alkene bond attacks the carbonyl group of the second benzaldehyde.  The ultimate products of ylide and benzoin are produced.  The ylide is the regenerated catalyst and performs the mechanism again.

 

The production of benzoin

As the second step of the multistep synthesis, the alcohol group of benzoin must be oxidized.  By utilizing the mild oxidizing agent of nitiric acid, benzoin was oxidized to produce benzil through the mechanism in scheme 2.

benzoin and nitric acid

The final mechanism, shown in scheme 3, involves the synthesis of the carboxylate salt intermediate, potassium benzilate, which drives the reaction to produce benzilic acid through workup.

The formation of benzilic acid

Results and Discussion For the first reaction, the presence of crystals after the combination of the ylide and benzaldehyde appeared pale yellow, solid but mushy.  After filtration, a total of 4.68 g of crude benzoin were collected.  Through recrystallization, a pure product of 2.07 g was collected, which produced a 44% yield.  This product produced a melting point of 129-132 °C.  This corresponds to the melting point of the crude product concluding that purification failed.  Purification could have been improved by adding more 95% ethanol to wash the crude product.  The final product of benzoin contained 13C NMR peaks at 199.2 ppm accounting for the carbonyl group and eight peaks in the range of 139.0-127.8 ppm representing the alkene bonds as well as the carbons of the aromatic rings.  Finally, a peak at 76.2 ppm represented the carbon with the alcohol group attached.  Regarding the 1H NMR spectra, four multiplet peaks appeared in the range of 7.79 and 7.14 ppm representing the hydrogens surrounding the aromatic rings.  A peak at 5.82 ppm accounted for the hydrogen attached to the carbon containing the alcohol group.  A peak at 3.92 ppm represented the hydrogen of the alcohol group.  An impurity of ethanol appeared at 4.42 ppm.  Finally, the IR spectra displayed a peak at 3403 cm-1 representing the C-H stretches, a peak at 3003 cm-1, accounting for the alcohol group, and a strong peak at 1761 cm-1 representing the carbonyl group.  Overall, the spectra confirmed the condensation of benzoin.

When benzoin was reacted with nitric acid, an orange/red color appeared.  When this mixture was heated and refluxed, a strong red color appeared in the reflux condenser, proving the presence of nitric gas.  A total of 1.91 g of purified benzil was produced from this reaction which contained an observed melting point of 89-92 °C and a 77% yield.  This appeared to be less than the ideal melting point of 95 °C, which could account for the lack of purity.  The 13C NMR produced a peak at 192.0 ppm representing the two carbonyl groups.  Four peaks appeared between 132.3 and 126.5 ppm accounting for the carbons within the aromatic ring and the alkene bonds.  The 1H NMR displayed three multiplet peaks at 7.86, 7.56, and 7.53 ppm representing the hydrogens around the aromatic ring that coupled with the surrounding hydrogens.  Finally, the IR spectrum produced a C-H stretch peak at 3010 cm-1 and a carbonyl peak at 1668    cm-1.  This data proved the success of the oxidation of benzoin to produce benzil.

For the final reaction, once benzil and aqueous potassium hydroxide were combined, the reaction turned from black to brown.  This intermediate step produced potassium benzilate.  After workup, a total of 0.41 g of the crystallized product were collected, which produced a melting point of 151-152 °C and a 17% yield.  The melting point corresponded to the known melting point of 150 °C. The 13C NMR spectra displayed a weak peak at 175.8 ppm, which accounted for the carbonyl group within the carboxylic acid.  Four peaks at 141.4, 128.3, 128.2, and 127.4 ppm represented the carbons within the aromatic rings.  Finally, a peak at 82.0 ppm represented the carbon attached to the alcohol group.  The 1H NMR spectrum produced a peak at 7.47 and 7.26 ppm representing the two groups of equivalent hydrogens attached to the aromatic rings.  A peak at 2.18 ppm represented the hydrogen of the alcohol group.  A peak did not appear at 12 ppm that would have represented the hydrogen of the carboxylic group, which means the reaction was not carried to completion.  In the IR spectrum, a hydroxyl peak appeared at 3399 cm-1.  A broad peak appeared at 2889 cm-1 representing the carboxylic acid functional group of compound.  Finally, a peak at 1718 cm-1 represented the carbonyl group and a peak at 1177 cm-1 accounted for the carbon-oxygen bond in both alcohol groups.  From this data and the low percent yield, the rearrangement of benzil was not achieved successfully.

 

Conclusion Through the multistep reaction, a 44% yield of benzoin, a 77% yield of benzil, and a 17% yield of benzilic acid were obtained.  The IR and 1H NMR data displayed peaks that allowed for the distinction and identification of the different products that led to the ultimate synthesis of benzilic acid.

 

Experimental

General: All reagents were provided by Texas A&M University Chemistry Department. 1H and 13C spectra were taken on a Mercury 300 MHz NMR spectrometer.  An IR spectrum was provided by PerkinElmer UATR Two Spectrophotometer.

 

Benzoin: Thaimine hydrochloride (1.52 g, 0.45 mmol), water (2mL) and 95% ethanol (15 mL) were combined in a 50-mL Erlenmeyer flask and swirled until dissolved and homogeneous.  Aqueous sodium hydroxide (4.5 mL) was added and swirled until the solution appeared pale yellow.  Finally, pure benzaldehyde (4.5 mL, 4.41 mmol) was added to the flask and the mixture was stored for two days.  The crystals that formed at room temperature were placed in an ice bath and then filtered under vacuum.  The crystals were washed with 5-mL portions of ice-cold water and left to dry.  To isolate the pure product, the crude material was crystallized with 95% ethanol (24 mL).  The pure product of benzoin showed the following physical characteristics: 2.07 g (44.3 % yield) mp: 129-132°C (lit: 135-135 °C).  1H NMR (CDCl3, 300 MHz) δ: 7.79 (d, J=1.5, 2H) 7.25 (m, 2H), 7.24 (m, 2H), 7.19 (m, 2H), 7.14 (m, 2H), 5.82 (d, J= 1.2, 1H), 3.92 (s, 1H) ppm.  13C NMR (CDCl3, 75Hz) δ: 199.2, 139.2, 139.1, 134.0, 129.2, 129.1, 128.7, 128.5, 127.8, 76.2 ppm.  IR 3403, 3003, 1761, 1203 cm-1.

 

Benzil: Benzoin (2.51g, 1.18 mmol), concentrated nitric acid (12 mL, 28.8 mmol), and a stir bar were placed into a 25-mL round-bottom flask with a water condenser and heated in a hot water bath at 70 °C for one hour.  After heating and magnetically stirring, the mixture was added to 40 mL of cool water and stirred until crystallized into a yellow solid.  Vacuum filtration was used to collect the crude product.  The pure product was collected through recrystallization by using 95% ethanol (20 mL).  The product displayed the following properties: 1.91 g (76.8 % yield) mp: 89-92 °C (lit: 95 °C).  1H NMR (CDCl3, 300 MHz) δ: 7.86 (m, 4H), 7.56 (m, 2H), 7.53 (m, 4H) ppm.  13C NMR (CDCl3, 75Hz) δ: 192.0, 132.3, 130.4, 127.3, 126.5 ppm.  IR 3010 (w), 1668 (s) cm-1.

Benzilic Acid: Benzil (2.10 g, 1.0 mmol), 95% ethanol (6 mL), and a boiling stone were added to a 25-mL round-bottom flask with a reflux condenser and heated until the solid benzil was dissolved.  Aqueous potassium hydroxide (5 mL, 18.2 mmol) was added dropwise to the flask and the mixture was boiled for 15 minutes.  The mixture was cooled, transferred to a beaker, and placed in an ice-water bath until crystallized.  The crystals were isolated through vacuum filtration and washed with 4-mL portions of cold 95% ethanol.  The solid was transferred to a 100-mL flask of hot water (60 mL) and mixed until completely dissolved.  Concentrated hydrochloric acid (1.3 mL) was added drop-wise until a permanent solid was present and a pH of 2 was maintained.  The solution was cooled in an ice bath and the crystals were filtered through vacuum filtration and washed with 2, 30-mL portions of ice-cold water.  The remaining crystals were identified by the following properties: 0.41 g (17.4% yield) mp: 151-152 °C (lit: 150 °C).  1H NMR (CDCl3, 300 MHz) δ: 7.47 (m, 6H), 7.26 (s, 4H), 2.18 (s, 1H) ppm.  13C NMR (CDCl3, 75Hz) δ: 175.8, 141.4, 128.3, 128.2, 127.4, 82.0 ppm.  IR 3399 (s), 2889 (s, b), 1718 (s), 1177 (s) cm-1.

Supporting information IR, 1H NMR and 13C NMR spectra of benzil, benzoin, and benzilic acid are attached.

 

1 Bruggink, A.; Schoevaart, R.; Kieboom, T. Org. Proc. Res. Dev., 2002, 7, 622-640.

2 Pavia, L; Lampman, G; Kriz, G; Engel, R. A Small Scale Approach to Organic Laboratory   Techniques, 2011, 266-269.

3 Lachman, A. J. Am. Chem. Soc., 1922, 44, 330-340.

 

Chemical Kinetics

By: Colleen Tuttle

Abstract

            Chemical kinetics determines the overall order of the reaction, as well as the order of each of the reactants.  In this lab, a series of reactions, with slight variations in concentrations were completed so the overall order of the reaction could be determined.

Introduction

            Chemical kinetics is the study of determining the rate of a reaction under certain conditions.  The rate law of a reaction uses the kinetic information of the concentrations at various times of the reactants in the experiment.  The method of determining this rate of reaction used commonly is called Pseudo-Orders.  Pseudo-orders are based on the initial concentrations of the reactants, and the rate law is then determined experimentally, since the rate will be measured during the experiment.  The rate expression for pseudo-orders is given by R=k[A]x[B]y, where A and B are the reactants, x and y are the individual orders, and k is the rate constant.  X, y, and k can only be determined experimentally.  When determining the individual orders for the reactants, one of the concentrations must be kept constant.  If one was to determine the value of x, the concentration of reactant B would need to be kept constant, while the concentration of reactant A was changed, which would, in turn, also affect the rate.  These values are then inputted into the equation above and divided by one another.  By keeping the concentration of B constant, that term has been eliminated from the equation, as has the rate constant, k.  This leaves the equation as the R1/R2=([A]1/[A]2)x, and from this, y can be determined by taking the log of both sides of the equation, and then simple division.  Y is determined in the same manner, only by keeping the concentration of reactant A constant.  After x and y have determined, k can be calculated.  This is done by using each reaction and determining the individual k, then averaging all of them to determine the overall rate constant.  Using the same equation as above, k is determined from a simple algebraic equation of dividing the rate by the concentration of A taken to its order and the concentration of B taken to its order.  Simply written, it is k = R/([A]x[B]y). After all the individual rate constants have determined and averaged, the final rate law can be written.2

The quantities of x, y, and k can only be obtained through experimental data because they are empirical numbers.  Therefore, if these same reactions were done under different conditions than originally performed, the values may be different.  Temperature, concentrations of the reactants, impurities, and the presence of catalysts can all affect the values of x, y, and k.1

 

Experimental Procedure

            Numerous steps were completed several times during this experiment to obtain all of the data needed to compile the final rate law.  Before the experiments could be started, the solutions needed to be made.  The potassium iodide (KI) solution was made by weighing out 20.75g of KI into a beaker, dissolving that in distilled water, adding that to a 500mL volumetric flask, and then filled to the fill line on the neck with distilled water, making sure to wash the original beaker containing the KI well, to get all of the compound into solution.  The Na2S2O3 solution was made in the same manner, using 7.906g of Na2S2O3 dissolved into a beaker and then added to a separate volumetric flask.  The hydrogen peroxide (H2O2) was readily available at any drug store, and the starch solution was prepared using 1-2g of starch dissolved into 500mL of distilled water and then heated.

A series of mini reactions were then preformed in test tubes.  To one test tube, 5mL of KI was added to 5 drops of H2O2; this solution was then distributed to 3 additional test tubes.  The first of the three test tubes was used as a control, to the second test tube, 3-4 drops of starch was added, and to the third, 1-2mL of Na2S2O3 was added, then 3 drops of starch added.

The main reactions were conducted in beakers, four at a time. For the first set of reactions, the volume of KI was changed, whereas in the second set of reactions, the volume of H2O2 was changed.  See the table below for exact values.  All of the reactants were placed into the beaker at the same time except the H2O2, which was added the very end, to measure the rate of the reaction.  Once the H2O2 was added, the solution was stirred and timed until the color change first appeared.  This procedure was repeated for each of the eight reactions.

data and observations
reactions
reactions 2
reactions 3
reactions 4
reactions 5
reactions 6

 

reactions 7
reactions 8
reactions 0

Conclusion

            In this experiment, numerous smaller reactions were carried out to demonstrate the chemical kinetics properties of rate laws.  During this experiment, the rate was determined by how long it took to create the color change.  This color change was from colorless to blue, then yellow/brown, which is from the reaction between the iodine and the starch, very similar to the color seen in iodine antiseptic wipes.  These reactions allowed the rate to be determined, and the rate constant to be evaluated from the graph of the log( R) v. log(I-) and log( R) v. log(H2O2) respectively.  From this data, it can be concluded that the reaction has an overall order of 2 and that the I- and H2O2 both have individual orders of 1.

 

References

1. Lecine, Ira N. 2002. Physical Chemistry. Fifth Edition.

2. Ngeyi, Stanley-Pierre, Ph.D. (2014) Physical Chemistry Notes. Madonna University. Livonia, MI