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Experiment #5: An Unexpected Reaction of 2,3-dimethyl-2,3-butanediol Author: TAs: Lab Section: AB1 Date: 10/11/2022
Objective: Purify via fractional distillation and determine the identity of the unexpected product of the acid-catalyzed reaction of 2,3-methyl-2,3-butanediol via IR, NMR, and boiling point analyses. Introduction: The pinacol rearrangement reaction was discovered in 1860, but despite being around for so long, it still continues to be applied to various industries and cutting-edge research now, in the 21st century. The pinacol rearrangement reaction is important for synthesizing certain fertilizers, fungicides, and pesticides. It’s also used to make pharmaceutical drugs such as pinacidil and Stiripentol, which is used to . A study published in the European Journal of Medicinal Chemistry detailed the use of pinacol rearrangement in finding other anticonvulsant drugs as an alternative to Stiripentol. https://doi.org/10.1016/j.ejmech.2011.11.004 Balanced Equation for Formation of Diene: H 2 SO 4 C 6 H 14 O 2 ---------------> C 6 H 10 + 2 H 2 O Mechanism of Formation of Diene: Balanced Equation for Formation of Unexpected Product: H 2 SO 4 C 6 H 14 O 2 ------------> C 6 H 12 O + H 2 O
Mechanism of formation of unexpected product: Table of Reagents: Name Molecular weight (g/mol) Melting pt (c) Boiling pt (c) Density (g/cm³) Hazards 2,3-dimethyl-2,3-butanediol 118.174 40- 41 157-159 0.967 irritant 2,3-dimethyl-2,3-butanediol diene 82.143 ---- approx 70 ---- Sulfuric acid 98.079 10 337 1.83 Corrosive, irritant Dimethylformamide (DMF) 73.09 -61 153 0.948 Skin irritant NaCl 58.44 801 1465 2.16 ---- C6H12O (unknown) 100.16 --- --- --- ---- Written Procedure / Observations: Procedure Summary Observations Put 3.6g of 2,3,dimethyl-2,3-butanediol, 10mL H2SO4 (3M), and stir bar in 25 mL round bottom flask. 3.604 g pinacol used Approx 11 mL H2SO4 Set up simple distillation and put receiving (25 mL round bottom) flask in ice water bath. Heat solution until receiving flask is half full. Heat set at 155C initially H2SO4 fizzled slightly when stir bar placed in → was it contaminated? Heat eventually turned up to 505C →
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hot plate not heating correctly Transfer distillate to separatory funnel and rinse receiving flask with little bit of water, add water to funnel, then drain aqueous layer. Distillate clear Solution being heated was murky white at first but turned dark brown by the end of the distillation Reaction flask was approx. ½ full Add 6 mL NaCl to funnel and swirl, stopper, shake it. Let stand for several mins. If no clear layer separation ask TA before adding 10 mL DCM. Separate organic layer. No DMF was added Distillate is clear Transfer organic layer to erlenmeyer flask, add MgSO4, while swirling, until doesn’t clump. Wet filter paper with DMF, filter into round bottom flask, wash product with 3 mL DMF. Purify product by fractional distillation -- cover with aluminum foil up to thermometer. Can be 2+ fractions (two in 70-75C boiling point range, one unknown). Record boiling point range for all and collect in pre-weighed flasks. F1: 32.908 g F2: 22.401 g F3 38.054 g Heat set at 220C Started rising rapidly at 28.1, dropped at 50.2 Rose rapidly to 83.3, dropped to 66.9 Rose to 94.5, dropped to 86.6 → F1 collected Then rose to 90.7, dropped to 84.4 → F2 collected Rose rapidly from 94.7 to 120.3, dropped → F3 collected Rest rose past 130C Obtain IR for each fraction. Make NMR sample of fraction that has carbonyl IR peak (aka the unknown). Measure mass of unknown. Carbonyl peak on 2nd fraction, used that for NMR F1: 63.434 F2 : 52.541 F3: 68.570 Formal Report Procedure: To a 25 mL round-bottom flask, 3.604 g of 2,3,dimethyl-2,3-butanediol and approx. 11 mL H 2 SO 4 (3M) was added. Using this, a simple fractional distillation was set up and allowed to run
until the receiving flask was half full. The distillate was then put in a separatory funnel and rinsed with water and 6 mL NaCl, then dried with MgSO 4 . The organic product was filtered into a round bottom flask and washed with 3 mL DMF. It was then purified by fractional distillation, and 3 fractions were collected. The boiling point for all fractions was noted. An IR spectra of all fractions was obtained, and an NMR sample of the second fraction was made, since it had a carbonyl peak in its IR. The weight of the third fraction, i.e, the unknown, was recorded (1.709g, 56.01% yield). The weights of the first two fractions, i.e, the diene, were also noted (1.179g and 68.71% yield for first fraction; 1.333g and 53.28% yield for second fraction). Theoretical Yields: 3.6g C6H14O2 * (1 mol/118.174g) * (1 mol diene / 1 mol C6H14O2) * (82.143g / 1 mol diene) = 2.502g diene 3.6g C6H14O2 * (1 mol / 118.174g) * (1 mol unknown / 1 mol C6H14O2) * (100.16g / 1 mol unknown) = 3.051g unknown Summary Table of Products: Weight of flask + cork for each fraction: Fraction 1: 32.908 + 28.807 = 61.715 g Fraction 2: 22.401 + 28.807 = 51.208 g Fraction 3: 38.054 + 28.807 = 66.861 g Product Experimental Yield Percent Yield Boiling Point (°C) Fraction 1 (diene)* 63.434 - 61.715 = 1.719 g (1.719 / 2.502) * 100 = 68.71% 86.8 – 94.5 Fraction 2 (diene)* 52.541 - 51.208 = 1.333 g (1.333 / 2.502) * 100 = 53.28% 84.4 – 90.7 Fraction 3 (unknown) 68.570 - 66.861 = 1.709 g (1.709 / 3.051) * 100 = 56.01% 94.7 – 120.3 *The combined weight of the two diene fractions exceeds the theoretical diene yield, suggesting experimental error. Summary Table for IR Spectral Data: Wavenumber (cm -1 ) Intensity (s, m, w) Functional Group
2873.83 - 2970.58 s Alkane C-H 1707.91 s Acyclic Ketone The IR data has two strong peaks in the 2800-3000 cm -1 region; this strongly suggests the presence of an alkane C-H in the structure of the molecule. There is also a strong peak at approximately 1700 cm -1 , suggesting the presence of an acyclic ketone. Summary Table for NMR Spectrum Data (include original printout with report) Labeled protons on unknown product corresponding to the NMR spectrum Assignment Chemical Shift (ppm) Splitting pattern Coupling Constant (Hz) Integration Comments A 2.24 singlet ---- N/A Unknown impurity B 2.13 singlet ---- N/A Unknown impurity C 1.38 singlet ---- 3 product D 0.39 singlet ---- 9 product Discussion: The formation of the unknown product is well-supported by the NMR and IR data; the NMR spectra has two singlet peaks, suggesting two unique hydrogens in the unknown product. The IR spectra contain peaks that correspond to alkane C-H and acyclic ketones; both of these outcomes are clearly supported by the chemical formula of the unknown product, C6H12O. The unknown was in the third fraction collected via distillation, and has a boiling point (94.7 – 120.3°C) that is significantly higher than the known diene collected in the two fractions before it.
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Overall, the experiment was rather unsuccessful, with significant errors being made during its execution that contributed greatly to data flaws such as inconsistent experimental yield and chemical impurities. The experimental yields of the first two fractions collected (which should have been dienes) should ideally have added up to 2.502g, the predicted theoretical diene yield. However, adding these two values exceeds the theoretical yield, suggesting that there was cross-contamination between the diene and the unknown product. Because of likely contamination, the yields are not a good gauge of experimental success. This is further supported by the fact that the second fraction, not the third, had a prominent acyclic ketone peak in its IR spectra, even though the second fraction should’ve been pure diene, and the third fraction should have been the unknown. In the NMR spectra, singlets A and B, at 2.24 and 2.13 ppm respectively, are not part of the unknown’s proton peaks; rather, they also indicate contamination. The experimentally-determined boiling point of the diene (ranges from 84.4 - 94.4°C) was notably higher than the expected boiling point of around 70°C; this is yet another indication of contamination. Because of this widespread impurity, likely caused by errors collecting fractions during the distillation, the unknown could not be successfully isolated and measured in the third fraction. When collecting the fractions, the temperature changes were not closely monitored, and fractions were allowed to undergo several significant temperature changes before they were collected. This experiment should be repeated and improved upon by more closely monitoring fluctuations in temperature during fractional distillation, so that the fractions are collected at the right time. Conclusion: The objective of this experiment was to isolate and identify the unknown in a pinacol rearrangement of 2,3,dimethyl-2,3-butanediol. 56.01% of the unknown was ultimately recovered. Although the product was formed (as indicated by the IR and NMR), severe contamination/impurities were present, which is indicated by the higher-than-expected boiling points, inconsistent percent yields, and extraneous NMR peaks. Post Lab Questions: 1. A B
C D 2. Diene: In a CNMR, I’d expect to see 3 signals, since there are 3 unique carbons present in the molecule. In an HNMR, there are 2 unique protons (2 signals expected) Proton A: integration = 2, multiplicity = 1, chemical shift = Proton B: integration = 3, multiplicity = 1, chemical shift = Unknown: In a CNMR, I’d expect to see 4 signals, since there are 4 unique carbons present in the molecule. In an HNMR, there are 2 unique protons (2 signals observed) Proton A: integration = 9, multiplicity = 1, chemical shift = 0.39 Proton B: integration = 3, multiplicity = 1, chemical shift = 1.38
3. (1) HCl is very volatile and would’ve gotten rid of all the acid, leading the reaction to not proceed. (2) Moreover, H2SO4 is hydroscopic; it removes water from the reaction, further driving the reaction forward. (3) Acid is used because it helps make alcohol a better leaving group.
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NMR Spectra: Assignment Chemical Shift (ppm) Splitting pattern Coupling Constant (Hz) Integration Comments A 2.24 singlet ---- N/A Unknown impurity B 2.13 singlet ---- N/A Unknown impurity C 1.38 singlet ---- 3 product D 0.39 singlet ---- 9 product